FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Waters, AM
Pittaway, M
Mogg, K
Bradley, BP
Pine, DS
AF Waters, Allison M.
Pittaway, Michelle
Mogg, Karin
Bradley, Brendan P.
Pine, Daniel S.
TI Attention training towards positive stimuli in clinically anxious
children
SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE
LA English
DT Article
DE Attention bias; Anxiety; Attention bias modification training; Cognitive
behavioural therapy
ID GENERALIZED ANXIETY DISORDER; CHILDHOOD ANXIETY; EXPERIMENTAL
MANIPULATION; MODIFICATION PROGRAM; BIAS; INDIVIDUALS; VULNERABILITY;
SYMPTOMS; THERAPY; THREAT
AB Objective: Attention bias modification training (ABMT) is a promising treatment. Nevertheless, few studies examine its effectiveness in anxious children. This study examined the efficacy of such an ABMT protocol in pediatric anxiety.
Method: 37 anxious children were randomly assigned to one of two ABMT conditions. In the attention-towards-positive (ATP) condition, children searched 3 x 3 matrices for a happy face amongst angry faces. In the attention-training-control (ATC) condition, they searched for a bird amongst flowers. Children completed 160 trials in each of four training sessions per week for three weeks at home (1920 total trials). Clinical and attention bias measures were assessed before and after ABMT.
Results: Children randomized to ATP showed greater post-training attention bias towards happy faces than children randomized to ATC. ATP also produced significantly greater reductions in clinician-rated diagnostic severity and number of diagnoses, compared to ATC. In the ATP group, 50% of children who completed training did not meet criteria for their principal diagnosis, compared to 8% in the ATC group.
Conclusion: Training anxious children to focus attention on positive features of their environment may be a promising treatment. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Waters, Allison M.; Pittaway, Michelle] Griffith Univ, Sch Appl Psychol, Mt Gravatt, Qld 4122, Australia.
[Mogg, Karin; Bradley, Brendan P.] Univ Southampton, Sch Psychol, Southampton SO9 5NH, Hants, England.
[Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, NIH, Bethesda, MD 20892 USA.
RP Waters, AM (reprint author), Griffith Univ, Sch Appl Psychol, Mt Gravatt, Qld 4122, Australia.
EM a.waters@griffith.edu.au
RI Mogg, Karin/C-1181-2008; Bradley, Brendan/B-9724-2008;
OI Mogg, Karin/0000-0002-2738-7378; Waters, Allison/0000-0003-2453-793X;
Bradley, Brendan/0000-0003-2801-4271
FU Australian Research Council [DP1095536]
FX The Australian Research Council Grant DP1095536 supported this research.
NR 33
TC 40
Z9 43
U1 1
U2 40
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1878-9293
J9 DEV COGN NEUROS-NETH
JI Dev. Cogn. Neurosci.
PD APR
PY 2013
VL 4
SI SI
BP 77
EP 84
DI 10.1016/j.dcn.2012.09.004
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 113FJ
UT WOS:000316651600008
PM 23063461
ER
PT J
AU Wilson, TE
DeMarini, DM
Dertinger, SD
Engelward, BP
Hanawalt, PC
MacGregor, JT
Smith-Roe, SL
Witt, KL
Yauk, CL
Ljungman, M
Schwartz, JL
Klein, CB
AF Wilson, Thomas E.
DeMarini, David M.
Dertinger, Stephen D.
Engelward, Bevin P.
Hanawalt, Philip C.
MacGregor, James T.
Smith-Roe, Stephanie L.
Witt, Kristine L.
Yauk, Carole L.
Ljungman, Mats
Schwartz, Jeffrey L.
Klein, Catherine B.
TI Building on the past, shaping the future: The environmental mutagenesis
and genomics society
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Article
DE genetics; epigenetics; toxicology; DNA repair; mutation research;
mutagen
ID GENETIC TOXICOLOGY; ORIGINS
AB In late 2012, the members of the Environmental Mutagen Society voted to change its name to the Environmental Mutagenesis and Genomics Society. Here, we describe the thought process that led to adoption of the new name, which both respects the rich history of a Society founded in 1969 and reflects the many advances in our understanding of the nature and breadth of gene-environment interactions during the intervening 43 years. Environ. Mol. Mutagen. 54:153157, 2013. (c) 2013 Wiley Periodicals, Inc.
C1 [Wilson, Thomas E.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
[Wilson, Thomas E.] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA.
[DeMarini, David M.] US EPA, Integrated Syst Toxicol Div, Res Triangle Pk, NC 27711 USA.
[Dertinger, Stephen D.] Litron Labs, Rochester, NY USA.
[Engelward, Bevin P.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Hanawalt, Philip C.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
[MacGregor, James T.] Toxicol Consulting Serv, Bonita Springs, FL USA.
[Smith-Roe, Stephanie L.; Witt, Kristine L.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Yauk, Carole L.] Hlth Canada, Environm Hlth Sci & Res Bur, Ottawa, ON K1A 0L2, Canada.
[Ljungman, Mats] Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI USA.
[Ljungman, Mats] Univ Michigan, Sch Med, Translat Oncol Program, Ann Arbor, MI USA.
[Schwartz, Jeffrey L.] Univ Washington, Sch Med, Dept Radiat Oncol, Seattle, WA 98195 USA.
[Klein, Catherine B.] NYU, Sch Med, Dept Environm Med, Tuxedo Pk, NY USA.
RP Wilson, TE (reprint author), Univ Michigan, Sch Med, Dept Pathol, 2065 BSRB,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA.
EM wilsonte@umich.edu
OI Yauk, Carole/0000-0003-4919-876X
NR 11
TC 0
Z9 0
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD APR
PY 2013
VL 54
IS 3
BP 153
EP 157
DI 10.1002/em.21765
PG 5
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 107OM
UT WOS:000316227700001
PM 23444128
ER
PT J
AU Siitonen, A
Majounie, E
Federoff, M
Ding, J
Majamaa, K
Singleton, AB
AF Siitonen, A.
Majounie, E.
Federoff, M.
Ding, J.
Majamaa, K.
Singleton, A. B.
TI Mutations in EIF4G1 are not a common cause of Parkinson's disease
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Letter
DE 1000 genomes; DNA sequencing; neurodegenerative diseases; Sanger; single
nucleotide polymorphism
C1 [Siitonen, A.; Majamaa, K.] Univ Oulu, Dept Clin Med, FIN-90014 Oulu, Finland.
[Siitonen, A.; Majamaa, K.] Oulu Univ Hosp, Dept Neurol, Oulu, Finland.
[Majounie, E.; Federoff, M.; Ding, J.; Singleton, A. B.] NIA, Mol Genet Sect, Lab Neurogenet, NIH, Bethesda, MD 20892 USA.
RP Siitonen, A (reprint author), Univ Oulu, Dept Neurol, POB 5000, FIN-90014 Oulu, Finland.
EM Ari.Siitonen@iki.fi
RI Singleton, Andrew/C-3010-2009
FU Intramural NIH HHS; NIA NIH HHS [Z01 AG000958-09]
NR 6
TC 7
Z9 7
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-5101
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD APR
PY 2013
VL 20
IS 4
BP e59
EP e59
DI 10.1111/ene.12051
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 107ZC
UT WOS:000316258800003
PM 23490116
ER
PT J
AU Larsen, BR
Steffensen, SDR
Nielsen, NVL
Friis, S
Godiksen, S
Bornholdt, J
Soendergaard, C
Nonboe, AW
Andersen, MN
Poulsen, SS
Szabo, R
Bugge, TH
Lin, CY
Skovbjerg, H
Jensen, JK
Vogel, LK
AF Larsen, Brian R.
Steffensen, Simon D. R.
Nielsen, Nis V. L.
Friis, Stine
Godiksen, Sine
Bornholdt, Jette
Soendergaard, Christoffer
Nonboe, Annika W.
Andersen, Martin N.
Poulsen, Steen S.
Szabo, Roman
Bugge, Thomas H.
Lin, Chen-Yong
Skovbjerg, Hanne
Jensen, Jan K.
Vogel, Lotte K.
TI Hepatocyte growth factor activator inhibitor-2 prevents shedding of
matriptase
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE Matriptase; HAI-2; HAI-1; Shedding
ID SERINE-PROTEASE INHIBITOR; PLACENTAL DEVELOPMENT; ZYMOGEN ACTIVATION;
BARRIER FUNCTION; EXPRESSION; CELLS; CARCINOGENESIS; PURIFICATION;
1/MATRIPTASE; ECTODOMAIN
AB Hepatocyte growth factor activator inhibitor-2 (HAI-2) is an inhibitor of many proteases in vitro, including the membrane-bound serine protease, matriptase. Studies of knock-out mice have shown that HAI-2 is essential for placental development only in mice expressing matriptase, suggesting that HAI-2 is important for regulation of matriptase. Previous studies have shown that recombinant expression of matriptase was unsuccessful unless co-expressed with another HAI, HAI-1. In the present study we show that when human matriptase is recombinantly expressed alone in the canine cell line MDCK, then human matriptase mRNA can be detected and the human matriptase ectodomain is shed to the media, suggesting that matriptase expressed alone is rapidly transported through the secretory pathway and shed. Whereas matriptase expressed together with HAI-1 or HAI-2 accumulates on the plasma membrane where it is activated, as judged by cleavage at Arg614 and increased peptidolytic activity of the cell extracts. Mutagenesis of Kunitz domain 1 but not Kunitz domain 2 abolished this function of HAI-2. HAI-2 seems to carry out its function intracellularly as this is where the vast majority of HAI-2 is located and since HAI-2 could not be detected on the basolateral plasma membrane where matriptase resides. However, minor amounts of HAI-2 not undergoing endocytosis could be detected on the apical plasma membrane. Our results suggest that Kunitz domain 1 of HAI-2 cause matriptase to accumulate in a membrane-bound form on the basolateral plasma membrane. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Larsen, Brian R.; Steffensen, Simon D. R.; Friis, Stine; Godiksen, Sine; Bornholdt, Jette; Soendergaard, Christoffer; Nonboe, Annika W.; Skovbjerg, Hanne; Vogel, Lotte K.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Cellular & Mol Med, DK-2200 Copenhagen N, Denmark.
[Nielsen, Nis V. L.; Jensen, Jan K.] Aarhus Univ, Fac Sci, Dept Mol Biol & Genet, Danish Chinese Ctr Proteases & Canc, DK-8000 Aarhus C, Denmark.
[Godiksen, Sine; Bornholdt, Jette] Univ Copenhagen, Fac Sci, Dept Biol, DK-2100 Copenhagen, Denmark.
[Andersen, Martin N.; Poulsen, Steen S.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Biomed Sci, DK-2200 Copenhagen N, Denmark.
[Szabo, Roman; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, NIH, Bethesda, MD 20892 USA.
[Lin, Chen-Yong] Univ Maryland, Greenebaum Canc Ctr, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
[Skovbjerg, Hanne] Amager Hosp, Dept Med, DK-2300 Copenhagen S, Denmark.
RP Vogel, LK (reprint author), Blegdamsvej 3,Bldg 18-4, DK-2200 Copenhagen N, Denmark.
EM vogel@sund.ku.dk
OI Soendergaard, Christoffer/0000-0002-2943-6911; Andersen, Martin
Nybo/0000-0003-1125-1553
FU Harboe Foundation; Brothers Hartmanns Foundation; A.P. Mollers
Foundation for the Advancement of Medical Science; Lundbeck Foundation;
Architect Holger Hjortenberg and Hustru Dagmar Hjortenbergs Foundation;
Else and Mogens Wedell-Wedellsborg Foundation; Aage and Johanne
Louis-Hansens Foundation; NIDCR; Danish Cancer Society
FX This work was supported by The Harboe Foundation, The Brothers Hartmanns
Foundation, The A.P. Mollers Foundation for the Advancement of Medical
Science, The Lundbeck Foundation, Architect Holger Hjortenberg and
Hustru Dagmar Hjortenbergs Foundation, Else and Mogens
Wedell-Wedellsborg Foundation, Aage and Johanne Louis-Hansens
Foundation, The NIDCR Intramural Programs and The Danish Cancer Society.
NR 28
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Z9 8
U1 1
U2 8
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
J9 EXP CELL RES
JI Exp. Cell Res.
PD APR 1
PY 2013
VL 319
IS 6
BP 918
EP 929
DI 10.1016/j.yexcr.2013.01.008
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 109NF
UT WOS:000316374600014
PM 23333561
ER
PT J
AU Jin, LY
Qin, LZ
Xia, DS
Liu, XB
Fan, ZP
Zhang, CM
Gu, LK
He, JQ
Ambudkar, IS
Deng, DJ
Wang, SL
AF Jin, Luyuan
Qin, Lizheng
Xia, Dengsheng
Liu, Xibao
Fan, Zhipeng
Zhang, Chunmei
Gu, Liankun
He, Junqi
Ambudkar, Indu S.
Deng, Dajun
Wang, Songlin
TI Active secretion and protective effect of salivary nitrate against
stress in human volunteers and rats
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Stress; Salivary glands; Saliva; Nitrate; Nitrite; Nitric oxide; Gastric
ulcer; Free radicals
ID DIETARY INORGANIC NITRATE; MUCOSAL BLOOD-FLOW; NITRIC-OXIDE;
PAROTID-GLANDS; GERM-FREE; GENERATION; PRESSURE; PLASMA; CANCER;
THERAPEUTICS
AB Up to 25% of the circulating nitrate in blood is actively taken up, concentrated, and secreted into saliva by the salivary glands. Salivary nitrate can be reduced to nitrite by the commensal bacteria in the oral cavity or stomach and then further converted to nitric oxide (NO) in vivo, which may play a role in gastric protection. However, whether salivary nitrate is actively secreted in human beings has not yet been determined. This study was designed to determine whether salivary nitrate is actively secreted in human beings as an acute stress response and what role salivary nitrate plays in stress-induced gastric injury. To observe salivary nitrate function under stress conditions, alteration of salivary nitrate and nitrite was analyzed among 22 healthy volunteers before and after a strong stress activity, jumping down from a platform at the height of 68 m. A series of stress indexes was analyzed to monitor the stress situation. We found that both the concentration and the total amount of nitrate in mixed saliva were significantly increased in the human volunteers immediately after the jump, with an additional increase 1 h later (p < 0.01). Saliva nitrite reached a maximum immediately after the jump and was maintained 1 h later. To study the biological functions of salivary nitrate and nitrite in stress protection, we further carried out a water-immersion-restraint stress (WIRS) assay in male adult rats with bilateral parotid and submandibular duct ligature (BPSDL). Intragastric nitrate, nitrite, and NO; gastric mucosal blood flow; and gastric ulcer index (UI) were monitored and nitrate was administrated in drinking water to compensate for nitrate secretion in BPSDL animals. Significantly decreased levels of intragastric nitrate, nitrite, and NO and gastric mucosal blood flow were measured in BPSDL rats during the WIRS assay compared to sham control rats (p < 0.05). Recovery was observed in the BPSDL rats upon nitrate administration. The WIRS-induced UI was significantly higher in the BPSDL animals compared to controls, and nitrate administration rescued the WIRS-induced gastric injury in BPSDL rats. In conclusion, this study suggests that stress promotes salivary nitrate secretion and nitrite formation, which may play important roles in gastric protection against stress-induced injury via the nitrate-dependent NO pathway. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Jin, Luyuan; Qin, Lizheng; Xia, Dengsheng; Fan, Zhipeng; Zhang, Chunmei; Wang, Songlin] Capital Med Univ, Sch Stomatol, Salivary Gland Dis Ctr, Beijing 100050, Peoples R China.
[Jin, Luyuan; Qin, Lizheng; Xia, Dengsheng; Fan, Zhipeng; Zhang, Chunmei; Wang, Songlin] Capital Med Univ, Sch Stomatol, Beijing Key Lab Tooth Regenerat & Funct Reconstru, Beijing 100050, Peoples R China.
[Liu, Xibao; Ambudkar, Indu S.] NIDCR, Mol Physiol & Therapeut Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Gu, Liankun; Deng, Dajun] Peking Univ, Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res, Minist Educ,Div Etiol, Beijing 100142, Peoples R China.
[He, Junqi; Wang, Songlin] Capital Med Univ, Sch Basic Med, Dept Biochem & Mol Biol, Beijing 100069, Peoples R China.
RP Deng, DJ (reprint author), Peking Univ, Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res, Minist Educ,Div Etiol, Beijing 100142, Peoples R China.
EM dengdajun@bjmu.edu.cn
RI Deng, Dajun/D-4605-2009
OI Deng, Dajun/0000-0001-5161-5943
FU National Natural Science Foundation of China [30430690, 30125042,
81170975]; Beijing Municipal Committee for Science and Technology
[Z121100005212004]
FX This study was supported by grants from the National Natural Science
Foundation of China (30430690, 30125042, and 81170975) and Beijing
Municipal Committee for Science and Technology (Z121100005212004). The
authors acknowledge the volunteers who participated in this study.
NR 38
TC 12
Z9 12
U1 2
U2 23
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 APR
PY 2013
VL 57
BP 61
EP 67
DI 10.1016/j.freeradbiomed.2012.12.015
PG 7
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 105AC
UT WOS:000316037000007
PM 23277147
ER
PT J
AU Doroshow, JH
Gaur, S
Markel, S
Lu, J
van Balgooy, J
Synold, TW
Xi, BX
Wu, XW
Juhasz, A
AF Doroshow, James H.
Gaur, Shikha
Markel, Susan
Lu, Jiamo
van Balgooy, Josephus
Synold, Timothy W.
Xi, Bixin
Wu, Xiwei
Juhasz, Agnes
TI Effects of iodonium-class flavin dehydrogenase inhibitors on growth,
reactive oxygen production, cell cycle progression, NADPH oxidase 1
levels, and gene expression in human colon cancer cells and xenografts
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE NADPH oxidase; Nox1; Diphenyleneiodonium; Colon cancer; Gene expression;
Free radicals
ID SMOOTH-MUSCLE-CELLS; S-PHASE-TRANSITION; DIPHENYLENE IODONIUM; OXIDATIVE
STRESS; PROTEIN-KINASE; NOX FAMILY; ACTIVATION; ROS; OVEREXPRESSION;
NEUTROPHILS
AB Iodonium-class flavoprotein dehydrogenase inhibitors have been demonstrated to possess antiproliferative potential and to inhibit reactive oxygen production in human tumor cells, although the mechanism(s) that explains the relationship between altered cell growth and the generation of reactive oxygen species (ROS) remains an area of active investigation. Because of the ability of these compounds to inhibit the activity of flavoprotein-containing epithelial NADPH oxidases, we chose to examine the effects of several iodonium-class flavoprotein inhibitors on human colon cancer cell lines that express high, functional levels of a single such oxidase (NADPH oxidase 1, or Nox1). We found that diphenyleneiodonium. (DPI); di-2-thienyliodonium (DTI), and iodonium diphenyl inhibited the growth of Caco2, HT-29, and LS-174 T colon cancer cells at concentrations (10-250 nM for DPI, 0.5-2.5 mu M for DTI, and 155 nM to 10 mu M for iodonium diphenyl) substantially lower than needed for DU145 human prostate cancer cells, which do not possess functional NADPH oxidase activity. Drug treatment was associated with decreased H2O2 production and diminished intracellular ROS levels, lasting up to 24 h, after short-term (1-h) exposure to the iodonium analogs. Decreased tumor cell proliferation was caused, in part, by a profound block in cell cycle progression at the G(1)/S interface in both LS-174 land HT-29 cells exposed to either DPI or DTI; and the G(1) block was produced, for LS-174 T cells, by upregulation of p27 and a drug concentration-related decrease in the expression of cyclins D1, A, and E that was partially prevented by exogenous H2O2. Not only did DPI and DTI decrease intracellular ROS, they both also significantly decreased the mRNA expression levels of Nox1, potentially contributing to the prolonged reduction in tumor cell reactive oxygen levels. We also found that DPI and DTI significantly decreased, the growth of both HT-29 and LS-174 T human tumor xenografts, at dose levels that produced peak plasma concentrations similar to those utilized for our in vitro experiments. These findings suggest that iodonium analogs have therapeutic potential for NADPH oxidase-containing human colon cancers. in vivo and that at least part of their antineoplastic mechanism of action may be related. to targeting Nox1 Published by Elsevier Inc.
C1 [Doroshow, James H.; Lu, Jiamo; Juhasz, Agnes] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Doroshow, James H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Gaur, Shikha; Markel, Susan; van Balgooy, Josephus; Synold, Timothy W.; Xi, Bixin] City Hope Comprehens Canc Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA.
[Wu, Xiwei] City Hope Comprehens Canc Ctr, Bioinformat Grp, Duarte, CA 91010 USA.
RP Doroshow, JH (reprint author), NCI, Div Canc Treatment & Diag, Bldg 31,Room 3A-4431,Ctr Dr NIH, Bethesda, MD 20892 USA.
EM doroshoj@mail.nih.gov
FU Center for Cancer Research; Division of Cancer Treatment and Diagnosis,
National Cancer Institute, National Institutes of Health
FX This work was supported by federal funds from the Center for Cancer
Research and the Division of Cancer Treatment and Diagnosis, National
Cancer Institute, National Institutes of Health. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. government.
NR 49
TC 11
Z9 11
U1 1
U2 13
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 APR
PY 2013
VL 57
BP 162
EP 175
DI 10.1016/j.freeradbiomed.2013.01.002
PG 14
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 105AC
UT WOS:000316037000016
PM 23314043
ER
PT J
AU McCauley, MP
Blake, KD
Meissner, HI
Viswanath, K
AF McCauley, M. P.
Blake, K. D.
Meissner, H. I.
Viswanath, K.
TI The social group influences of US health journalists and their impact on
the newsmaking process
SO HEALTH EDUCATION RESEARCH
LA English
DT Article
ID NATIONAL-SURVEY; MEDIA COVERAGE; CANCER CONTROL; NEWS MEDIA;
DISPARITIES; WOMEN; REPORTERS; SCIENCE; CARE; OPPORTUNITIES
AB The news media play a vital role in disseminating health information, yet little is known about the social characteristics of health journalists or the impact they have on the newsmaking process. This study examines how the social group influences of US health journalists impact two important aspects of news production-'media agenda-setting' and 'framing'. Using data from a national survey of health and medical science journalists, the authors conducted multivariable logistic regression analyses to study the links between the gender, age and race/ethnicity of respondents, and the ways in which they utilized news sources, other resources, news priorities and story angles. Female respondents were more likely than males to say that educating people to make informed decisions and disseminating new, accurate information are important priorities. Female and minority journalists were more likely than white males to use a variety of sources, and to say it is important to develop the health and scientific literacy of audiences and influence public health behaviors. The gender and race/ethnicity of journalists play an important role in the production of health news. Health educators can foster improved coverage by learning more about the life experiences of health journalists and developing better working relationships with them.
C1 [McCauley, M. P.; Viswanath, K.] Harvard Univ, Dept Soc Human Dev & Hlth, Sch Publ Hlth, Boston, MA 02215 USA.
[McCauley, M. P.; Viswanath, K.] Dana Farber Canc Inst, McGraw Patterson Ctr Populat Sci, Boston, MA 02215 USA.
[Blake, K. D.] NCI, Hlth Commun & Informat Res Branch, NIH, Bethesda, MD 20892 USA.
[Meissner, H. I.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
RP McCauley, MP (reprint author), Harvard Univ, Dept Soc Human Dev & Hlth, Sch Publ Hlth, Boston, MA 02215 USA.
EM michael_mccauley@dfci.harvard.edu
RI McCauley, Michael/C-3642-2014
OI McCauley, Michael/0000-0003-3851-1765
FU NCI NIH HHS [R25 CA057713]
NR 70
TC 7
Z9 7
U1 4
U2 26
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1153
J9 HEALTH EDUC RES
JI Health Educ. Res.
PD APR
PY 2013
VL 28
IS 2
BP 339
EP 351
DI 10.1093/her/cys086
PG 13
WC Education & Educational Research; Public, Environmental & Occupational
Health
SC Education & Educational Research; Public, Environmental & Occupational
Health
GA 108DY
UT WOS:000316273100013
PM 22907539
ER
PT J
AU Raza, MH
Gertz, EM
Mundorff, J
Lukong, J
Kuster, J
Schaffer, AA
Drayna, D
AF Raza, M. Hashim
Gertz, E. Michael
Mundorff, Jennifer
Lukong, Joseph
Kuster, Judith
Schaeffer, Alejandro A.
Drayna, Dennis
TI Linkage analysis of a large African family segregating stuttering
suggests polygenic inheritance
SO HUMAN GENETICS
LA English
DT Article
ID TWIN; PEDIGREES; GENOME; SAMPLE; EPIDEMIOLOGY; SIMULATION; DISORDERS;
MUTATIONS; CHILDREN; ETIOLOGY
AB We describe a pedigree of 71 individuals from the Republic of Cameroon in which at least 33 individuals have a clinical diagnosis of persistent stuttering. The high concentration of stuttering individuals suggests that the pedigree either contains a single highly penetrant gene variant or that assortative mating led to multiple stuttering-associated variants being transmitted in different parts of the pedigree. No single locus displayed significant linkage to stuttering in initial genome-wide scans with microsatellite and SNP markers. By dividing the pedigree into five subpedigrees, we found evidence for linkage to previously reported loci on 3q and 15q, and to novel loci on 2p, 3p, 14q, and a different region of 15q. Using the two-locus mode of Superlink, we showed that combining the recessive locus on 2p and a single-locus additive representation of the 15q loci is sufficient to achieve a two-locus score over 6 on the entire pedigree. For this 2p + 15q analysis, we show LOD scores ranging from 4.69 to 6.57, and the scores are sensitive to which marker is chosen for 15q. Our findings provide strong evidence for linkage at several loci.
C1 [Raza, M. Hashim; Mundorff, Jennifer; Lukong, Joseph; Drayna, Dennis] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA.
[Gertz, E. Michael; Schaeffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Kuster, Judith] Minnesota State Univ, Dept Speech Hearing & Rehabil Serv, Mankato, MN USA.
RP Drayna, D (reprint author), 5 Res Court,Room 2B-46, Rockville, MD 20850 USA.
EM drayna@nidcd.nih.gov
OI Gertz, E. Michael/0000-0001-8390-4387
FU Intramural Research Program of the NIH, NIDCD [Z01-000046-11]; NLM
[LM000097]; Stuttering Foundation
FX This study was supported by the Intramural Research Program of the NIH,
NIDCD (Z01-000046-11) and the NLM (LM000097), and by the Stuttering
Foundation. We are especially grateful to the members of family CAMST01
for their participation. We thank Bailey Levis for genotyping during the
early stages of this project, and Drs. Thomas Friedman and Robert Morell
for suggestions that improved the manuscript.
NR 46
TC 4
Z9 4
U1 0
U2 15
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD APR
PY 2013
VL 132
IS 4
BP 385
EP 396
DI 10.1007/s00439-012-1252-5
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 109DI
UT WOS:000316345400002
PM 23239121
ER
PT J
AU Sun, JL
Tao, S
Gao, Y
Peng, T
Tan, AH
Zhang, HY
Yang, XB
Qin, X
Hu, YL
Feng, JJ
Kim, ST
Lin, XL
Wu, YM
Zhang, J
Li, ZX
Li, L
Mo, LJ
Liang, ZJ
Shi, DY
Huang, Z
Huang, XH
Liu, M
Liu, Q
Zhang, SJ
Zheng, SL
Xu, JF
Mo, ZN
AF Sun, Jielin
Tao, Sha
Gao, Yong
Peng, Tao
Tan, Aihua
Zhang, Haiying
Yang, Xiaobo
Qin, Xue
Hu, Yanling
Feng, Junjie
Kim, Seong-Tae
Lin, Xiaoling
Wu, Yongming
Zhang, Ju
Li, Zhixian
Li, Li
Mo, Linjian
Liang, Zhengjia
Shi, Deyi
Huang, Zhang
Huang, Xianghua
Liu, Ming
Liu, Qian
Zhang, Shijun
Zheng, S. Lilly
Xu, Jianfeng
Mo, Zengnan
TI Genome-wide association study identified novel genetic variant on
SLC45A3 gene associated with serum levels prostate-specific antigen
(PSA) in a Chinese population
SO HUMAN GENETICS
LA English
DT Article
ID CANCER; MEN
AB Prostate-specific antigen (PSA) is a commonly used cancer biomarker for prostate cancer, and is often included as part of routine physical examinations in China. Serum levels of PSA may be influenced by genetic factors as well as other factors. A genome-wide association study (GWAS) conducted in a European population successfully identified six genetic loci that were significantly associated with PSA level. In this study, we aimed to identify common genetic variants that are associated with serum level of PSA in a Chinese population. We also evaluated the effects of those variants by creating personalized PSA cutoff values. A two-stage GWAS of PSA level was performed among men age 20-69 years and self-reported cancer-free participants that underwent routine physical examinations at several hospitals in Guangxi Province, China. Single nucleotide polymorphisms (SNPs) significantly associated with PSA levels in the first stage of sample (N = 1,999) were confirmed in the second stage of sample (N = 1,496). Multivariate linear regression was used to assess the independent contribution of confirmed SNPs and known covariates, such as age, to the level of PSA. SNPs in three regions were significantly associated with levels of PSA in this two-stage GWAS, and had combined P values between 4.62 x 10(-17) and 6.45 x 10(-37). The three regions are located on 1q32.1 at SLC45A3, 10q11.23 at MSMB, and 19q13.33 at KLK3. The region 1q32.1 at SLC45A3 was identified as a novel locus. Genetic variants contributed significantly more to the variance of PSA level than known covariates such as age. Personalized cutoff values of serum PSA, calculated based on the inheritance of these associated SNPs, differ considerably among individuals. Identification of these genetic markers provides new insight into the molecular mechanisms of PSA. Taking individual variation into account, these genetic variants may improve the performance of PSA to predict prostate cancer.
C1 [Sun, Jielin; Tao, Sha; Feng, Junjie; Kim, Seong-Tae; Zheng, S. Lilly; Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA.
[Gao, Yong; Wu, Yongming; Mo, Linjian; Mo, Zengnan] Guangxi Med Univ, Affiliated Hosp 1, Inst Urol & Nephrol, Nanning 530021, Guangxi, Peoples R China.
[Gao, Yong; Tan, Aihua; Zhang, Haiying; Yang, Xiaobo; Qin, Xue; Hu, Yanling; Li, Zhixian; Zhang, Shijun; Mo, Zengnan] Guangxi Med Univ, Ctr Genom & Personalized Med, Nanning 530021, Guangxi, Peoples R China.
[Peng, Tao] Guangxi Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Nanning 530021, Guangxi, Peoples R China.
[Peng, Tao] NCI, Lab Genom Divers, NIH, Frederick, MD 21701 USA.
[Zhang, Haiying; Yang, Xiaobo] Guangxi Med Univ, Sch Publ Hlth, Dept Occupat Hlth & Environm Hlth, Nanning 530021, Guangxi, Peoples R China.
[Qin, Xue] Guangxi Med Univ, Affiliated Hosp 1, Dept Clin Lab, Nanning 530021, Guangxi, Peoples R China.
[Hu, Yanling; Li, Li] Guangxi Med Univ, Med Sci Res Ctr, Nanning 530021, Guangxi, Peoples R China.
[Lin, Xiaoling; Xu, Jianfeng] Fudan Univ, Sch Life Sci, Fudan VARI Ctr Genet Epidemiol, Shanghai 200433, Peoples R China.
[Zhang, Ju] Nankai Univ, Coll Life Sci, Dept Biochem & Mol Biol, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China.
[Liang, Zhengjia; Shi, Deyi; Huang, Zhang] Fangchenggang First Peoples Hosp, Med Examinat Ctr, Fangchenggang, Guangxi, Peoples R China.
[Huang, Xianghua] Guigang Peoples Hosp, Med Examinat Ctr, Guigang, Guangxi, Peoples R China.
[Liu, Ming] Yulin First Peoples Hosp, Med Examinat Ctr, Yulin, Guangxi, Peoples R China.
[Liu, Qian] Guangxi Med Univ, Affiliated Hosp 1, Inst Cardiovasc Dis, Nanning 530021, Guangxi, Peoples R China.
[Xu, Jianfeng] Fudan Univ, Huashan Hosp, Inst Urol, Shanghai 200433, Peoples R China.
RP Mo, ZN (reprint author), Guangxi Med Univ, Affiliated Hosp 1, Inst Urol & Nephrol, Nanning 530021, Guangxi, Peoples R China.
EM zengnanmo@hotmail.com
RI Yang, Xiaobo/G-3854-2016; Kim, Seong-Tae/E-4474-2017
OI Kim, Seong-Tae/0000-0001-7436-1405
FU General Program of National Natural Science Foundation of China
[30945204, 30360124, 30260110]; Guangxi Provincial Department of Finance
and Education [2009GJCJ150]; Fudan-VARI Center for genetic Epidemiology;
Fudan University Institute of Urology
FX We thank the local research teams from Fangchenggang First People's
Hospital, Guigang People's Hospital and Yulin First People's Hospital
for their contribution to the recruitment of study subjects. We thank
X-W Zou, H-C Zheng and O Li at the Genergy Biotechnology (Shanghai) Co.,
Ltd, for their assistance in the genotyping. Finally, we thank all study
subjects for participating in the study. This work was partially
supported by the General Program of National Natural Science Foundation
of China (30945204, 30360124, 30260110), the Guangxi Provincial
Department of Finance and Education (2009GJCJ150), and intramural
funding from Fudan-VARI Center for genetic Epidemiology and intramural
funding from Fudan University Institute of Urology.
NR 17
TC 9
Z9 10
U1 2
U2 20
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
EI 1432-1203
J9 HUM GENET
JI Hum. Genet.
PD APR
PY 2013
VL 132
IS 4
BP 423
EP 429
DI 10.1007/s00439-012-1254-3
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 109DI
UT WOS:000316345400006
PM 23269536
ER
PT J
AU Ballew, BJ
Yeager, M
Jacobs, K
Giri, N
Boland, J
Burdett, L
Alter, BP
Savage, SA
AF Ballew, Bari J.
Yeager, Meredith
Jacobs, Kevin
Giri, Neelam
Boland, Joseph
Burdett, Laurie
Alter, Blanche P.
Savage, Sharon A.
TI Germline mutations of regulator of telomere elongation helicase 1,
RTEL1, in Dyskeratosis congenita
SO HUMAN GENETICS
LA English
DT Article
ID MULTIPLE SEQUENCE ALIGNMENT; SYNDROME GENE; T-COFFEE; VARIANTS; CANCER;
LENGTH; SUSCEPTIBILITY; ANTICIPATION; MAINTENANCE; COMPLEX
AB Dyskeratosis congenita (DC) is an inherited bone marrow failure and cancer predisposition syndrome caused by aberrant telomere biology. The classic triad of dysplastic nails, abnormal skin pigmentation, and oral leukoplakia is diagnostic of DC, but substantial clinical heterogeneity exists; the clinically severe variant Hoyeraal Hreidarsson syndrome (HH) also includes cerebellar hypoplasia, severe immunodeficiency, enteropathy, and intrauterine growth retardation. Germline mutations in telomere biology genes account for approximately one-half of known DC families. Using exome sequencing, we identified mutations in RTEL1, a helicase with critical telomeric functions, in two families with HH. In the first family, two siblings with HH and very short telomeres inherited a premature stop codon from their mother who has short telomeres. The proband from the second family has HH and inherited a premature stop codon in RTEL1 from his father and a missense mutation from his mother, who also has short telomeres. In addition, inheritance of only the missense mutation led to very short telomeres in the proband's brother. Targeted sequencing identified a different RTEL1 missense mutation in one additional DC proband who has bone marrow failure and short telomeres. Both missense mutations affect the helicase domain of RTEL1, and three in silico prediction algorithms suggest that they are likely deleterious. The nonsense mutations both cause truncation of the RTEL1 protein, resulting in loss of the PIP box; this may abrogate an important protein-protein interaction. These findings implicate a new telomere biology gene, RTEL1, in the etiology of DC.
C1 [Ballew, Bari J.; Giri, Neelam; Alter, Blanche P.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
[Yeager, Meredith; Jacobs, Kevin; Boland, Joseph; Burdett, Laurie] NCI, Canc Genom Res Lab, SAIC Frederick Inc, Frederick, MD 20877 USA.
RP Savage, SA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd EPS 7018, Rockville, MD 20892 USA.
EM savagesh@mail.nih.gov
RI Savage, Sharon/B-9747-2015
OI Savage, Sharon/0000-0001-6006-0740
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health; Westat, Inc. [N02-CP-91026, N02-CP-11019,
HHSN261200655001C]
FX This study was funded by the intramural research program of the Division
of Cancer Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health and by contracts N02-CP-91026, N02-CP-11019, and
HHSN261200655001C with Westat, Inc.
NR 36
TC 74
Z9 76
U1 0
U2 18
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD APR
PY 2013
VL 132
IS 4
BP 473
EP 480
DI 10.1007/s00439-013-1265-8
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 109DI
UT WOS:000316345400011
PM 23329068
ER
PT J
AU Perry, JRB
Corre, T
Esko, T
Chasman, DI
Fischer, K
Franceschini, N
He, CY
Kutalik, Z
Mangino, M
Rose, LM
Smith, AV
Stolk, L
Sulem, P
Weedon, MN
Zhuang, WV
Arnold, A
Ashworth, A
Bergmann, S
Buring, JE
Burri, A
Chen, C
Cornelis, MC
Couper, DJ
Goodarzi, MO
Gudnason, V
Harris, T
Hofman, A
Jones, M
Kraft, P
Launer, L
Laven, JSE
Li, G
McKnight, B
Masciullo, C
Milani, L
Orr, N
Psaty, BM
Ridker, PM
Rivadeneira, F
Sala, C
Salumets, A
Schoemaker, M
Traglia, M
Waeber, G
Chanock, SJ
Demerath, EW
Garcia, M
Hankinson, SE
Hu, FB
Hunter, DJ
Lunetta, KL
Metspalu, A
Montgomery, GW
Murabito, JM
Newman, AB
Ong, KK
Spector, TD
Stefansson, K
Swerdlow, AJ
Thorsteinsdottir, U
Van Dam, RM
Uitterlinden, AG
Visser, JA
Vollenweider, P
Toniolo, D
Murray, A
AF Perry, John R. B.
Corre, Tanguy
Esko, Tonu
Chasman, Daniel I.
Fischer, Krista
Franceschini, Nora
He, Chunyan
Kutalik, Zoltan
Mangino, Massimo
Rose, Lynda M.
Smith, Albert Vernon
Stolk, Lisette
Sulem, Patrick
Weedon, Michael N.
Zhuang, Wei V.
Arnold, Alice
Ashworth, Alan
Bergmann, Sven
Buring, Julie E.
Burri, Andrea
Chen, Constance
Cornelis, Marilyn C.
Couper, David J.
Goodarzi, Mark O.
Gudnason, Vilmundur
Harris, Tamara
Hofman, Albert
Jones, Michael
Kraft, Peter
Launer, Lenore
Laven, Joop S. E.
Li, Guo
McKnight, Barbara
Masciullo, Corrado
Milani, Lili
Orr, Nicholas
Psaty, Bruce M.
Ridker, Paul M.
Rivadeneira, Fernando
Sala, Cinzia
Salumets, Andres
Schoemaker, Minouk
Traglia, Michela
Waeber, Gerard
Chanock, Stephen J.
Demerath, Ellen W.
Garcia, Melissa
Hankinson, Susan E.
Hu, Frank B.
Hunter, David J.
Lunetta, Kathryn L.
Metspalu, Andres
Montgomery, Grant W.
Murabito, Joanne M.
Newman, Anne B.
Ong, Ken K.
Spector, Tim D.
Stefansson, Kari
Swerdlow, Anthony J.
Thorsteinsdottir, Unnur
Van Dam, Rob M.
Uitterlinden, Andre G.
Visser, Jenny A.
Vollenweider, Peter
Toniolo, Daniela
Murray, Anna
CA ReproGen Consortium
TI A genome-wide association study of early menopause and the combined
impact of identified variants
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID PREMATURE OVARIAN FAILURE; NATURAL MENOPAUSE; AGE; LOCI; HERITABILITY;
DAUGHTERS; SMOKING; MOTHERS
AB Early menopause (EM) affects up to 10 of the female population, reducing reproductive lifespan considerably. Currently, it constitutes the leading cause of infertility in the western world, affecting mainly those women who postpone their first pregnancy beyond the age of 30 years. The genetic aetiology of EM is largely unknown in the majority of cases. We have undertaken a meta-analysis of genome-wide association studies (GWASs) in 3493 EM cases and 13 598 controls from 10 independent studies. No novel genetic variants were discovered, but the 17 variants previously associated with normal age at natural menopause as a quantitative trait (QT) were also associated with EM and primary ovarian insufficiency (POI). Thus, EM has a genetic aetiology which overlaps variation in normal age at menopause and is at least partly explained by the additive effects of the same polygenic variants. The combined effect of the common variants captured by the single nucleotide polymorphism arrays was estimated to account for 30 of the variance in EM. The association between the combined 17 variants and the risk of EM was greater than the best validated non-genetic risk factor, smoking.
C1 [Perry, John R. B.; Weedon, Michael N.; Murray, Anna] Univ Exeter, Sch Med, Exeter EX1 2LU, Devon, England.
[Perry, John R. B.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Perry, John R. B.; Mangino, Massimo; Burri, Andrea; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
[Corre, Tanguy; Kutalik, Zoltan; Bergmann, Sven] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Corre, Tanguy; Kutalik, Zoltan; Bergmann, Sven] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Corre, Tanguy; Masciullo, Corrado; Sala, Cinzia; Traglia, Michela; Toniolo, Daniela] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy.
[Esko, Tonu; Fischer, Krista; Milani, Lili; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Esko, Tonu; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
[Salumets, Andres] Univ Tartu, Dept Obstet & Gynecol, EE-50090 Tartu, Estonia.
[Chasman, Daniel I.; Rose, Lynda M.; Buring, Julie E.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Chasman, Daniel I.; Buring, Julie E.; Kraft, Peter; Ridker, Paul M.; Hankinson, Susan E.; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Couper, David J.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[He, Chunyan] Indiana Univ Sch Med, Dept Publ Hlth, Indianapolis, IN USA.
[He, Chunyan] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
[Smith, Albert Vernon; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Stolk, Lisette; Rivadeneira, Fernando; Uitterlinden, Andre G.; Visser, Jenny A.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Hofman, Albert; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Laven, Joop S. E.] Erasmus MC, Div Reprod Med, Rotterdam, Netherlands.
[Stolk, Lisette; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Netherlands Consortium Hlth Aging, Rotterdam, Netherlands.
[Sulem, Patrick; Stefansson, Kari; Thorsteinsdottir, Unnur] Decode Genet, IS-105 Reykjavik, Iceland.
[Zhuang, Wei V.; Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Arnold, Alice; McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Li, Guo; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Ashworth, Alan; Orr, Nicholas] Inst Canc Res, Breakthrough Res Ctr, London SW3 6JB, England.
[Buring, Julie E.; Ridker, Paul M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Chen, Constance; Kraft, Peter; Hankinson, Susan E.; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Cornelis, Marilyn C.; Kraft, Peter; Hu, Frank B.; Hunter, David J.; Van Dam, Rob M.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Goodarzi, Mark O.] Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Bethesda, MD USA.
[Harris, Tamara; Launer, Lenore; Garcia, Melissa] NIA, NIH, Bethesda, MD 20892 USA.
[Jones, Michael; Schoemaker, Minouk; Swerdlow, Anthony J.] Inst Canc Res, Epidemiol Sect, Sutton SM2 5NG, Surrey, England.
[Kraft, Peter; Hankinson, Susan E.; Hu, Frank B.; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Salumets, Andres] Competence Ctr Reprod Med & Biol, Tartu, Estonia.
[Waeber, Gerard; Vollenweider, Peter] CHU Vaudois, Univ Lausanne Hosp, Div Internal Med, Lausanne, Switzerland.
[Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Demerath, Ellen W.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Montgomery, Grant W.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Ong, Ken K.] Addenbrookes Hosp, Inst Metab Sci, Epidemiol Unit, MRC, Cambridge, England.
[Ong, Ken K.] Univ Cambridge, Dept Paediat, Cambridge, England.
[Van Dam, Rob M.] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Van Dam, Rob M.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore.
[Toniolo, Daniela] Inst Mol Genet, I-27100 Pavia, Italy.
RP Murray, A (reprint author), Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX1 2LU, Devon, England.
EM anna.murray@pms.ac.uk
RI Smith, Albert Vernon/K-5150-2015; Montgomery, Grant/B-7148-2008;
Rivadeneira, Fernando/O-5385-2015; mangino, massimo/F-5134-2011; Colaus,
PsyColaus/K-6607-2013; van Dam, Rob/F-9674-2010; Newman,
Anne/C-6408-2013; Visser, Jenny /F-8156-2011; Salumets,
Andres/J-2278-2015; Milani, Lili/C-8759-2011; Gudnason,
Vilmundur/K-6885-2015;
OI Murray, Anna/0000-0002-2351-2522; Schoemaker,
Minouk/0000-0001-8403-2234; Esko, Tonu/0000-0003-1982-6569; Smith,
Albert Vernon/0000-0003-1942-5845; Montgomery,
Grant/0000-0002-4140-8139; Rivadeneira, Fernando/0000-0001-9435-9441;
mangino, massimo/0000-0002-2167-7470; Murabito,
Joanne/0000-0002-0192-7516; Lunetta, Kathryn/0000-0002-9268-810X; van
Dam, Rob/0000-0002-7354-8734; Newman, Anne/0000-0002-0106-1150;
Salumets, Andres/0000-0002-1251-8160; Milani, Lili/0000-0002-5323-3102;
Gudnason, Vilmundur/0000-0001-5696-0084; MARONGIU,
MARA/0000-0002-7321-2384
FU Wellcome Trust [092447/Z/10/Z]
FX J.R.B.P. is funded by the Wellcome Trust as a Sir Henry Wellcome
Postdoctoral Research Fellow (092447/Z/10/Z). Funding details for
individual studies is provided in supplementary information. Funding to
pay the Open Access publication charges for this article was provided by
the Wellcome Trust.
NR 26
TC 33
Z9 34
U1 2
U2 17
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 APR 1
PY 2013
VL 22
IS 7
BP 1465
EP 1472
DI 10.1093/hmg/dds551
PG 8
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 108MH
UT WOS:000316297000018
PM 23307926
ER
PT J
AU Galis, ZS
Thrasher, T
Reid, DM
Stanley, DV
Oh, YS
AF Galis, Zorina S.
Thrasher, Terry
Reid, Diane M.
Stanley, Dennis V.
Oh, Young S.
TI Investing in High Blood Pressure Research A National Institutes of
Health Perspective
SO HYPERTENSION
LA English
DT Review
ID HEART; HYPERTENSION; LUNG; ASSOCIATION; DISEASE; RISK
C1 [Galis, Zorina S.; Thrasher, Terry; Reid, Diane M.; Stanley, Dennis V.; Oh, Young S.] NHLBI, Div Cardiovasc Sci, Vasc Biol & Hypertens Branch, NIH, Bethesda, MD 20892 USA.
RP Galis, ZS (reprint author), NHLBI, Vasc Biol & Hypertens Branch, Div Cardiovasc Sci, 6701 Rockledge Dr,8116, Bethesda, MD 20892 USA.
EM zorina.galis@nih.gov
NR 32
TC 13
Z9 13
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD APR
PY 2013
VL 61
IS 4
BP 757
EP +
DI 10.1161/HYPERTENSIONAHA.111.00770
PG 9
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 106AC
UT WOS:000316112800014
PM 23438933
ER
PT J
AU Mewton, N
Opdahl, A
Choi, EY
Almeida, ALC
Kawel, N
Wu, CO
Burke, GL
Liu, ST
Liu, K
Bluemke, DA
Lima, JAC
AF Mewton, Nathan
Opdahl, Anders
Choi, Eui-Young
Almeida, Andre L. C.
Kawel, Nadine
Wu, Colin O.
Burke, Gregory L.
Liu, Songtao
Liu, Kiang
Bluemke, David A.
Lima, Joao A. C.
TI Left Ventricular Global Function Index by Magnetic Resonance Imaging-A
Novel Marker for Assessment of Cardiac Performance for the Prediction of
Cardiovascular Events The Multi-Ethnic Study of Atherosclerosis
SO HYPERTENSION
LA English
DT Article
DE ejection fraction; heart failure; left ventricle; LV global function
index; LV mass
ID HYPERTENSIVE HEART-DISEASE; EJECTION FRACTION; MYOCARDIAL FIBROSIS;
SYSTOLIC FUNCTION; RISK-FACTORS; FAILURE; MASS; GEOMETRY; OUTCOMES;
DYSFUNCTION
AB Left ventricular (LV) function is generally assessed independent of structural remodeling and vice versa. The purpose of this study was to evaluate a novel LV global function index (LVGFI) that integrates LV structure with global function and to assess its predictive value for cardiovascular (CV) events throughout adult life in a multiethnic population of men and women without history of CV diseases at baseline. A total of 5004 participants in the Multi-Ethnic Study of Atherosclerosis underwent a cardiac magnetic resonance study and were followed up for a median of 7.2 years. The LVGFI by cardiac magnetic resonance was defined by the ratio of stroke volume divided by LV total volume defined as the sum of mean LV cavity and myocardial volumes. Cox proportional hazard models were constructed to predict the end points of heart failure, hard CV events, and a combined end point of all CV events after adjustment for established risk factors, calcium score, and biomarkers. A total of 579 (11.6%) CV events were observed during the follow-up period. In adjusted models, the end points of heart failure, hard CV events, and all events were all significantly associated with LVGFI (heart failure, hazard ratio=0.64, P<0.0001; hard CV events, hazard ratio=0.79, P=0.007; all events, hazard ratio=0.79, P<0.0001). LVGFI had a significant independent predictive value in the multivariable models for all CV event categories. The LVGFI was a powerful predictor of incident HF, hard CV events, and a composite end point, including all events in this multiethnic cohort. (Hypertension. 2013;61:770-778.). Online Data Supplement
C1 [Mewton, Nathan; Opdahl, Anders; Choi, Eui-Young; Almeida, Andre L. C.; Lima, Joao A. C.] Johns Hopkins Univ Hosp, Sch Med, Div Cardiol, Dept Med, Baltimore, MD 21287 USA.
[Wu, Colin O.] NHLBI, Bethesda, MD 20892 USA.
[Burke, Gregory L.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
[Liu, Kiang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Liu, Songtao; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
[Kawel, Nadine] NIH, Bethesda, MD 20892 USA.
[Mewton, Nathan] Hop Cardiovasc & Pneumol Louis Pradel, Ctr Invest, Clin Lyon, Lyon, France.
[Opdahl, Anders] Oslo Univ Hosp, Rikshosp, Dept Cardiol, Oslo, Norway.
RP Lima, JAC (reprint author), Johns Hopkins Univ Hosp, 600 North Wolfe St,Blalock 524D1, Baltimore, MD 21287 USA.
EM jlima@jhmi.edu
RI Opdahl, Anders/I-7580-2015;
OI Opdahl, Anders/0000-0002-0599-592X; Bluemke, David/0000-0002-8323-8086
FU National Heart, Lung, and Blood Institute supported [N01-HC-95159,
N01-HC-95169]; French Federation of Cardiology; Raagholt Research
Foundation; Norwegian Cardiovascular Society; Musaeus Aarsvold
Foundation; US-Norway Fulbright Foundation; Sorensen Research
Foundation, Oslo, Norway
FX The National Heart, Lung, and Blood Institute supported this project
(contracts N01-HC-95159 through N01-HC-95169). The French Federation of
Cardiology supported Dr Nathan Mewton with a Post-Doctoral Research
Grant at the Johns Hopkins Hospital. The Raagholt Research Foundation
supported Dr Anders Opdahl with a Post-Doctoral Research Grant at the
Johns Hopkins Hospital. The Norwegian Cardiovascular Society supported
Dr Anders Opdahl with a Post-Doctoral Research Grant at the Johns
Hopkins Hospital. The Musaeus Aarsvold Foundation supported Dr Anders
Opdahl with a Post-Doctoral Research Grant at the Johns Hopkins
Hospital. The US-Norway Fulbright Foundation supported Dr Anders Opdahl
with a Post-Doctoral Research Grant at the Johns Hopkins Hospital. The
Sorensen Research Foundation, Oslo, Norway, supported Dr Anders Opdahl
with a Post-Doctoral Research Grant at the Johns Hopkins Hospital.
NR 31
TC 19
Z9 20
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD APR
PY 2013
VL 61
IS 4
BP 770
EP +
DI 10.1161/HYPERTENSIONAHA.111.198028
PG 18
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 106AC
UT WOS:000316112800018
PM 23424238
ER
PT J
AU Saveria, T
Oleinikov, AV
Wiliamson, K
Chaturvedi, R
Lograsso, J
Keitany, GJ
Fried, M
Duffy, P
AF Saveria, Tracy
Oleinikov, Andrew V.
Wiliamson, Kathryn
Chaturvedi, Richa
Lograsso, Joe
Keitany, Gladys J.
Fried, Michal
Duffy, Patrick
TI Antibodies to Escherichia coli-Expressed C-Terminal Domains of
Plasmodium falciparum Variant Surface Antigen 2-Chondroitin Sulfate A
(VAR2CSA) Inhibit Binding of CSA-Adherent Parasites to Placental Tissue
SO INFECTION AND IMMUNITY
LA English
DT Article
ID PREGNANCY-ASSOCIATED MALARIA; CROSS-REACTIVE ANTIBODIES;
CHONDROITIN-SULFATE; INFECTED ERYTHROCYTES; BLOCKING ANTIBODIES; VAR
GENE; ADHESION; PFEMP1; TRANSCRIPTION; TRANSMISSION
AB Placental malaria (PM) is characterized by infected erythrocytes (IEs) that selectively bind to chondroitin sulfate A (CSA) and sequester in placental tissue. Variant surface antigen 2-CSA (VAR2CSA), a Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) protein family member, is expressed on the surface of placental IEs and mediates adherence to CSA on the surface of syncytiotrophoblasts. This transmembrane protein contains 6 Duffy binding-like (DBL) domains which might contribute to the specific adhesive properties of IEs. Here, we use laboratory isolate 3D7 VAR2CSA DBL domains expressed in Escherichia coli to generate antibodies specific for this protein. Flow cytometry results showed that antibodies generated against DBL4 epsilon, DBL5 epsilon, DBL6 epsilon, and tandem double domains of DBL4-DBL5 and DBL5-DBL6 all bind to placental parasite isolates and to lab strains selected for CSA binding but do not bind to children's parasites. Antisera to DBL4 epsilon and to DBL5 epsilon inhibit maternal IE binding to placental tissue in a manner comparable to that for plasma collected from multigravid women. These antibodies also inhibit binding to CSA of several field isolates derived from pregnant women, while antibodies to double domains do not enhance the functional immune response. These data support DBL4 epsilon and DBL5 epsilon as vaccine candidates for pregnancy malaria and demonstrate that E. coli is a feasible tool for the large-scale manufacture of a vaccine based on these VAR2CSA domains.
C1 [Saveria, Tracy; Oleinikov, Andrew V.; Wiliamson, Kathryn; Chaturvedi, Richa; Lograsso, Joe; Keitany, Gladys J.; Duffy, Patrick] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Fried, Michal; Duffy, Patrick] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
[Fried, Michal; Duffy, Patrick] Univ Washington, Dept Global Hlth, Program Pathobiol, Seattle, WA 98195 USA.
RP Duffy, P (reprint author), Seattle Biomed Res Inst, 4 Nickerson St, Seattle, WA 98109 USA.
EM patrick.duffy@nih.gov
FU Bill and Melinda Gates Foundation
FX Support for this work was provided by a grant from the Bill and Melinda
Gates Foundation.
NR 38
TC 5
Z9 5
U1 0
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD APR
PY 2013
VL 81
IS 4
BP 1031
EP 1039
DI 10.1128/IAI.00978-12
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 108RM
UT WOS:000316313700002
PM 23319559
ER
PT J
AU Fukuda, Y
Tsai, HF
Myers, TG
Bennett, JE
AF Fukuda, Yuichi
Tsai, Huei-Fung
Myers, Timothy G.
Bennett, John E.
TI Transcriptional Profiling of Candida glabrata during Phagocytosis by
Neutrophils and in the Infected Mouse Spleen
SO INFECTION AND IMMUNITY
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; OXIDATIVE STRESS; GENE-EXPRESSION; ALBICANS;
DEGRADATION; RESISTANCE; VIRULENCE; PATHWAYS; MICE
AB Expression microarray analysis of Candida glabrata following phagocytosis by human neutrophils was performed, and results were compared with those from C. glabrata incubated under conditions of carbohydrate or nitrogen deprivation. Twenty genes were selected to represent the major cell processes altered by phagocytosis or nutrient deprivation. Quantitative real-time PCR (qRT-PCR) with TaqMan chemistry was used to assess expression of the same genes in spleens of mice infected intravenously with Candida glabrata. The results in spleen closely paralleled gene expression in neutrophils or following carbohydrate deprivation. Fungal cells responded by upregulating alternative energy sources through gluconeogenesis, glyoxylate cycle, and long-chain fatty acid metabolism. Autophagy was likely employed to conserve intracellular resources. Aspartyl protease upregulation occurred and may represent defense against attacks on cell wall integrity. Downregulated genes were in the pathways of protein and ergosterol synthesis. Upregulation of the sterol transport gene AUS1 suggested that murine cholesterol may have been used to replace ergosterol, as has been reported in vitro. C. glabrata isolates in spleens of gp91(phox-/-) knockout mice with reduced oxidative phagocyte defenses were grossly similar although with a reduced level of response. These results are consistent with reported results of other fungi responding to phagocytosis, indicating that a rapid shift in metabolism is required for growth in a carbohydrate-limited intracellular environment.
C1 [Fukuda, Yuichi; Tsai, Huei-Fung; Bennett, John E.] NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Myers, Timothy G.] NIAID, Genom Technol Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jbennett@niaid.nih.gov
FU Division of Intramural Research, NIAID
FX This work was supported by the Division of Intramural Research, NIAID.
NR 32
TC 12
Z9 35
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD APR
PY 2013
VL 81
IS 4
BP 1325
EP 1333
DI 10.1128/IAI00851-12
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 108RM
UT WOS:000316313700029
PM 23403555
ER
PT J
AU Wu, YZ
Antony, S
Hewitt, SM
Jiang, GJ
Yang, SX
Meitzler, JL
Juhasz, A
Lu, JM
Liu, H
Doroshow, JH
Roy, K
AF Wu, Yonghzong
Antony, Smitha
Hewitt, Stephen M.
Jiang, Guojian
Yang, Sherry X.
Meitzler, Jennifer L.
Juhasz, Agnes
Lu, Jiamo
Liu, Han
Doroshow, James H.
Roy, Krishnendu
TI Functional activity and tumor-specific expression of dual oxidase 2 in
pancreatic cancer cells and human malignancies characterized with a
novel monoclonal antibody
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE dual oxidase; NADPH oxidase; reactive oxygen species; pancreatic cancer;
gene expression
ID GENE-EXPRESSION; HYDROGEN-PEROXIDE; NADPH OXIDASES; DUOX GENES;
INFLAMMATION; PROTEINS; ADJACENT; TISSUES; ROS
AB Dual oxidase 2 (Duox2), one of the seven members of the NADPH oxidase gene family, plays a critical role in generating H2O2, for thyroid hormone biosynthesis and as an integral part of the host defense system of the respiratory epithelium and the gastrointestinal tract. Recent evidence suggests that the regulation of Duox2 expression is under the control of pro-inflammatory cytokines and that Duox2-induced reactive oxygen species (ROS) contribute to the inflammation-related tissue injury that occurs in two pre-malignant, inflammatory conditions: chronic pancreatitis and inflammatory bowel disease. Because no reliable Duox antibodies are commercially available, we report the development of a murine monoclonal antibody (MAb) to Duox2 (clone Duox S-12) and its use for the characterization of Duox2 expression in human tumors, tumor cell lines and normal tissues. Duox S-12 specifically detected both endogenously- and ectopically-expressed Duox2 protein by immunoblotting, immunofluorescence microscopy and immunohistochemistry (where both membranous and cytoplasmic staining were present). Duox2 expression detected by Duox S-12 was functionally coupled to the generation of H2O2, in pancreatic cancer cells that expressed Duox2 and its cognate maturation factor DuoxA2. Although Duox S-12 recognizes ectopically expressed Duox1 protein because of the extensive amino acid homology between Duox1 and Duox2, the lack of substantial Duoxl mRNA expression in human tumors (except thyroid cancer) allowed us to evaluate Duox2 expression across a wide range of normal and malignant tissues by immunohistochemistry. Duox2 was expressed at elevated levels in many human cancers, most notably tumors of the prostate, lung, colon and breast while brain tumors and lymphomas demonstrated the lowest frequency of expression. The Duox-specific monoclonal antibody described here provides a promising tool for the further examination of the role of Duox-dependent reactive oxygen production in inflammation-related carcinogenesis, where alterations in oxidant tone play a critical role in cell growth and proliferation.
C1 [Wu, Yonghzong; Antony, Smitha; Jiang, Guojian; Meitzler, Jennifer L.; Juhasz, Agnes; Lu, Jiamo; Liu, Han; Doroshow, James H.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Yang, Sherry X.; Meitzler, Jennifer L.; Doroshow, James H.; Roy, Krishnendu] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
RP Doroshow, JH (reprint author), NCI, Div Canc Treatment & Diag, Bldg 31,Room 3A-44,31 Ctr Dr, Bethesda, MD 20892 USA.
EM doroshoj@mail.nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788
FU Division of Cancer Treatment and Diagnosis; Center for Cancer Research
of the National Cancer Institute, National Institutes of Health
FX This study was supported by the Division of Cancer Treatment and
Diagnosis and the Center for Cancer Research of the National Cancer
Institute, National Institutes of Health. The content of this
publication does not necessarily reflect the views of 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. In addition, we wish to thank Dr Thomas Leto
of the National Institute of Allergy and Infectious Diseases, NIH for
his kind gift of the HA-Duox1 plasmid and Dr Helmut Grasberger, of the
University of Michigan, for his kind gift of the HA-Duox2 and Myc-DuoxA2
plasmids.
NR 25
TC 12
Z9 12
U1 1
U2 10
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 APR
PY 2013
VL 42
IS 4
BP 1229
EP 1238
DI 10.3892/ijo.2013.1821
PG 10
WC Oncology
SC Oncology
GA 111HA
UT WOS:000316511200013
PM 23404210
ER
PT J
AU Azad, N
Dasari, A
Arcaroli, J
Taylor, GE
Laheru, DA
Carducci, MA
McManus, M
Quackenbush, K
Wright, JJ
Hidalgo, M
Diaz, LA
Donehower, RC
Zhao, M
Rudek, MA
Messersmith, WA
AF Azad, Nilofer
Dasari, Arvind
Arcaroli, John
Taylor, Gretchen E.
Laheru, Daniel A.
Carducci, Michael A.
McManus, Martine
Quackenbush, Kevin
Wright, John J.
Hidalgo, Manuel
Diaz, Luis A., Jr.
Donehower, Ross C.
Zhao, Ming
Rudek, Michelle A.
Messersmith, Wells A.
TI Phase I pharmacokinetic and pharmacodynamic study of cetuximab,
irinotecan and sorafenib in advanced colorectal cancer
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE Sorafenib; Cetuximab; Irinotecan; Pharmacokinetics; Colorectal cancer
ID ENDOTHELIAL GROWTH-FACTOR; ANTITUMOR-ACTIVITY; SOLID TUMORS; PLUS
IRINOTECAN; RAS MUTATIONS; III TRIAL; CHEMOTHERAPY; COMBINATION;
RECEPTOR; BEVACIZUMAB
AB Background This phase Ib study was designed to determine the maximum tolerated doses (MTD) and dose limiting toxicities (DLTs) of irinotecan and cetuximab with sorafenib. Secondary objectives included characterizing the pharmacokinetics and pharmacodynamics and evaluating preliminary antitumor activity in patients with advanced colorectal cancer (CRC). Methods Patients with metastatic, pretreated CRC were treated at five dose levels. Results Eighteen patients were recruited with median age 56.5 years. In the first five patients treated, 2 irinotecan related DLTs were observed. With reduced dose intensity irinotecan, there were no further DLTs. The most common toxicities were diarrhea, nausea/vomiting, fatigue, anorexia and rash. DLTs included neutropenia and thrombocytopenia. Two patients had partial responses (one with a KRAS mutation) and 8 had stable disease (8-36 weeks). The median progression free survival (PFS) and overall survival (OS) were 2.5 and 4.7 months respectively. Pharmacokinetic analyses suggest sorafenib and metabolite exposure correlate with OS and DLTs. Conclusions The recommended phase II dose (RP2D) is irinotecan 100 mg/m(2) i.v. days 1, 8; cetuximab 400 mg/m(2) i.v. days 1 and 250 mg/m(2) i.v. weekly; and sorafenib 400 mg orally twice daily in advanced, pretreated CRC. The combination resulted in a modest response rate.
C1 [Azad, Nilofer; Taylor, Gretchen E.; Laheru, Daniel A.; Carducci, Michael A.; Hidalgo, Manuel; Diaz, Luis A., Jr.; Donehower, Ross C.; Zhao, Ming; Rudek, Michelle A.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
[Dasari, Arvind; Arcaroli, John; McManus, Martine; Quackenbush, Kevin; Messersmith, Wells A.] Univ Colorado, Ctr Canc, Aurora, CO 80045 USA.
[Wright, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Rudek, MA (reprint author), Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Bunting Blaustein Canc Res Bldg,Room 1M52,1650 Or, Baltimore, MD 21231 USA.
EM mrudek2@jhmi.edu; Wells.Messersmith@ucdenver.edu
RI HIDALGO, MANUEL/I-4995-2015
OI HIDALGO, MANUEL/0000-0002-3765-3318
FU NIH/NCI [1K23CA115500, 1R21CA117125, U01 CA070095]; Analytical
Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at
Johns Hopkins (NIH) [P30 CA006973, UL1 RR025005]; National Center for
Research Resources (NCRR), a component of the National Institutes of
Health (NIH) [UL1RR025005]; NIH Roadmap for Medical Research; Bayer
(major) via University of Colorado Cancer Center
FX This research was supported by NIH/NCI grant 1K23CA115500 (WM),
1R21CA117125 (WM), U01 CA070095 (MC), and the Analytical Pharmacology
Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
(NIH grants P30 CA006973 and UL1 RR025005). This publication was made
possible by Grant Number UL1RR025005 from the National Center for
Research Resources (NCRR), a component of the National Institutes of
Health (NIH), and NIH Roadmap for Medical Research. Its contents are
solely the responsibility of the authors and do not necessarily
represent the official view of NCRR or NIH.; Dr. Messersmith has
received commercial clinical research grant support from Bayer (major)
via University of Colorado Cancer Center.
NR 34
TC 5
Z9 6
U1 1
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD APR
PY 2013
VL 31
IS 2
BP 345
EP 354
DI 10.1007/s10637-012-9820-z
PG 10
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 105OQ
UT WOS:000316081900010
PM 22615057
ER
PT J
AU Stewart, BA
Klar, AJS
AF Stewart, Barbara A.
Klar, Amar J. S.
TI Can Bronchoscopic Airway Anatomy Be an Indicator of Autism?
SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
LA English
DT Article
DE Autism; Autism spectrum disorder etiology; Doublets; Airway double
branching; Airway anomaly
ID SPECTRUM DISORDERS; EARLY INTERVENTION; DIAGNOSIS; CHILDREN; DEFINITION;
PREVALENCE; LOBE; AGE
AB Bronchoscopic evaluations revealed that some children have double branching of bronchi (designated "doublets") in the lower lungs airways, rather than normal, single branching. Retrospective analyses revealed only one commonality in them: all subjects with doublets also had autism or autism spectrum disorder (ASD). That is, 49 subjects exhibited the presence of initial normal anatomy in upper airway followed by doublets in the lower airway. In contrast, the normal branching pattern was noted in all the remaining 410 subjects who did not have a diagnosis of autism/ASD. We propose that the presence of doublets might be an objective, reliable, and valid biologic marker of autism/ASD.
C1 [Stewart, Barbara A.] St Josephs Hosp, Pediat Pulm Dept, Childrens Hlth Ctr, Phoenix, AZ 85013 USA.
[Klar, Amar J. S.] NIH, Gene Regulat & Chromosome Biol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Stewart, BA (reprint author), St Josephs Hosp, Pediat Pulm Dept, Childrens Hlth Ctr, Phoenix, AZ 85013 USA.
EM tinkdoc@cox.net; klara@mail.nih.gov
FU Intramural NIH HHS
NR 37
TC 1
Z9 1
U1 2
U2 6
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 APR
PY 2013
VL 43
IS 4
BP 911
EP 916
DI 10.1007/s10803-012-1635-4
PG 6
WC Psychology, Developmental
SC Psychology
GA 109KG
UT WOS:000316365400015
PM 22926922
ER
PT J
AU Prasad, V
Jorgenson, J
Ioannidis, JPA
Cifu, A
AF Prasad, Vinay
Jorgenson, Joel
Ioannidis, John P. A.
Cifu, Adam
TI Observational studies often make clinical practice recommendations: an
empirical evaluation of authors' attitudes
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Review
DE Epidemiology; Clinical trials; Observational studies; Randomized trials;
Hierarchy of research design; Reversal
ID CONTROLLED-TRIALS; MEDICAL REVERSAL; CANCER; EPIDEMIOLOGY; FALSE
AB Objectives: Although observational studies provide useful descriptive and correlative information, their role in the evaluation of medical interventions remains contentious. There has been no systematic evaluation of authors' attitudes toward their own nonrandomized studies and how often they recommend specific medical practices.
Study Design and Setting: We reviewed all original articles of nonrandomized studies published in 2010 in New England Journal of Medicine, Lancet, Journal of the American Medical Association, and Annals of Internal Medicine, We classified articles based on whether authors recommend a medical practice and whether they state that a randomized trial is needed to support their recommendation. We also examined the types of logical extrapolations used by authors who did advance recommendations.
Results: Of the 631 original articles published in 2010, 298 (47%) articles were eligible observational studies. In 167 (56%) of 298 studies, authors recommended a medical practice based on their results. Only 24 (14%) of 167 studies stated that a randomized controlled trial (RCT) should be done to validate the recommendation, whereas the other 143 articles made a total of 149 logical extrapolations to recommend specific medical practices. Recommendations without a call for a randomized trial were most common in studies of modifiable factors (59%), but they were also common in studies reporting incidence or prevalence (51%), studies examining novel tests (41%), and association studies of nonmodifiable factors (32%).
Conclusion: The authors of observational studies often extrapolate their results to make recommendations concerning a medical practice, typically without first calling for a RCT. Published by Elsevier Inc.
C1 [Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Jorgenson, Joel] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Ioannidis, John P. A.] Stanford Univ, Dept Med, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA.
[Ioannidis, John P. A.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Cifu, Adam] Univ Chicago, Med Ctr, Dept Med, Pritzker Sch Med, Chicago, IL 60637 USA.
RP Cifu, A (reprint author), Univ Chicago, Med Ctr, Dept Med, Pritzker Sch Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM acifu@medicine.bsd.uchicago.edu
NR 33
TC 27
Z9 27
U1 2
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0895-4356
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD APR
PY 2013
VL 66
IS 4
BP 361
EP 366
DI 10.1016/j.jclinepi.2012.11.005
PG 6
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 103QX
UT WOS:000315935100004
PM 23384591
ER
PT J
AU Austin, PC
Tu, JV
Ho, JE
Levy, D
Lee, DS
AF Austin, Peter C.
Tu, Jack V.
Ho, Jennifer E.
Levy, Daniel
Lee, Douglas S.
TI Using methods from the data-mining and machine-learning literature for
disease classification and prediction: a case study examining
classification of heart failure subtypes
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Article
DE Boosting; Classification trees; Bagging; Random forests; Classification;
Regression trees; Support vector machines; Regression methods;
Prediction; Heart failure
ID REDUCED EJECTION FRACTION; LOGISTIC-REGRESSION; MORTALITY; TREES
AB Objective: Physicians classify patients into those with or without a specific disease. Furthermore, there is often interest in classifying patients according to disease etiology or subtype. Classification trees are frequently used to classify patients according to the presence or absence of a disease. However, classification trees can suffer from limited accuracy. In the data-mining and machine-learning literature, alternate classification schemes have been developed. These include bootstrap aggregation (bagging), boosting, random forests, and support vector machines.
Study Design and Setting: We compared the performance of these classification methods with that of conventional classification trees to classify patients with heart failure (HF) according to the following subtypes: HF with preserved ejection fraction (HFPEF) and HF with reduced ejection fraction. We also compared the ability of these methods to predict the probability of the presence of HFPEF with that of conventional logistic regression.
Results: We found that modern, flexible tree-based methods from the data-mining literature offer substantial improvement in prediction and classification of HF subtype compared with conventional classification and regression trees. However, conventional logistic regression had superior performance for predicting the probability of the presence of HFPEF compared with the methods proposed in the data-mining literature.
Conclusion: The use of tree-based methods offers superior performance over conventional classification and regression trees for predicting and classifying HF subtypes in a population-based sample of patients from Ontario, Canada. However, these methods do not offer substantial improvements over logistic regression for predicting the presence of HFPEF. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Austin, Peter C.; Tu, Jack V.; Lee, Douglas S.] Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada.
[Austin, Peter C.; Tu, Jack V.; Lee, Douglas S.] Univ Toronto, Inst Hlth Management Policy & Evaluat, Toronto, ON, Canada.
[Austin, Peter C.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Tu, Jack V.] Univ Toronto, Div Cardiol, Sunnybrook Schulich Heart Ctr, Toronto, ON, Canada.
[Tu, Jack V.; Lee, Douglas S.] Univ Toronto, Fac Med, Toronto, ON, Canada.
[Ho, Jennifer E.; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Ho, Jennifer E.; Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Ho, Jennifer E.] Boston Univ, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
[Levy, Daniel] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Lee, Douglas S.] Univ Toronto, Univ Hlth Network, Dept Med, Toronto, ON, Canada.
RP Austin, PC (reprint author), Inst Clin Evaluat Sci, G106,2075 Bayview Ave, Toronto, ON M4N 3M5, Canada.
EM peter.austin@ices.on.ca
RI Lee, Douglas/J-4315-2014;
OI Ho, Jennifer/0000-0002-7987-4768; Austin, Peter/0000-0003-3337-233X
FU Institute for Clinical Evaluative Sciences (ICES); Ontario Ministry of
Health and Long-Term Care (MOHLTC); Canadian Institutes of Health
Research (CIHR) [MOP 86508]; Heart and Stroke Foundation; Canada
Research Chair in Health Services Research; Career Investigator Award
from the Heart and Stroke Foundation; CIHR Team Grant in Cardiovascular
Outcomes Research
FX This study was supported by the Institute for Clinical Evaluative
Sciences (ICES), which is funded by an annual grant from the Ontario
Ministry of Health and Long-Term Care (MOHLTC). The opinions, results,
and conclusions reported in this article are those of the authors and
are independent from the funding sources. No endorsement by ICES or the
Ontario MOHLTC is intended or should be inferred. This research was
supported by an operating grant from the Canadian Institutes of Health
Research (CIHR) (MOP 86508). Dr Austin is supported in part by a Career
Investigator award from the Heart and Stroke Foundation. Dr Tu is
supported by a Canada Research Chair in Health Services Research and a
Career Investigator Award from the Heart and Stroke Foundation. Dr Lee
is a clinician-scientist of the CIHR. The data used in this study were
obtained from the Enhanced Feedback for Effective Cardiac Treatment
(EFFECT) study. The EFFECT study was funded by a CIHR Team Grant in
Cardiovascular Outcomes Research.
NR 38
TC 28
Z9 28
U1 5
U2 37
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0895-4356
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD APR
PY 2013
VL 66
IS 4
BP 398
EP 407
DI 10.1016/j.jclinepi.2012.11.008
PG 10
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 103QX
UT WOS:000315935100010
PM 23384592
ER
PT J
AU Hamidovic, A
Goodloe, RJ
Young, TR
Styn, MA
Mukamal, KJ
Choquet, H
Kasberger, JL
Buxbaum, SG
Papanicolaou, GJ
White, W
Volcik, K
Spring, B
Hitsman, B
Levy, D
Jorgenson, E
AF Hamidovic, Ajna
Goodloe, Robert J.
Young, Taylor R.
Styn, Mindi A.
Mukamal, Kenneth J.
Choquet, Helene
Kasberger, Jay L.
Buxbaum, Sarah G.
Papanicolaou, George J.
White, Wendy
Volcik, Kelly
Spring, Bonnie
Hitsman, Brian
Levy, Daniel
Jorgenson, Eric
TI Genetic Analysis of a Population Heavy Drinking Phenotype Identifies
Risk Variants in Whites
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE alcohol consumption; alcoholism; cholecystokinin;
methylenetetrahydrofolate dehydrogenase
ID GENOME-WIDE ASSOCIATION; ALCOHOL-CONSUMPTION; PLASMA HOMOCYSTEINE;
ENVIRONMENTAL CONTRIBUTIONS; ANTISOCIAL PERSONALITY; CHOLECYSTOKININ
GENE; PROMOTER REGION; FEMALE TWINS; SAMPLE; DEPENDENCE
AB Genetic association studies thus far have used detailed diagnoses of alcoholism to identify loci associated with risk. This proof-of-concept analysis examined whether population data of lifetime heaviest alcohol consumption may be used to identify genetic loci that modulate risk We conducted a genetic association study in European Americans between variants in approximately 2100 genes and alcohol consumption as part of the Candidate gene Association Resource project. We defined cases as individuals with a history of drinking 5 or more drinks per day almost every day of the week and controls as current light drinkers (1-5 drinks per week). We cross-validated identified single nucleotide polymorphisms in a meta-analysis of 2 cohorts of unrelated individuals-Atherosclerosis Risk in. Communities (ARIC) and Cardiovascular Health Study (CHS)-and in a separate cohort of related individuals -Framingham Heart Study (FHS). The most significant variant in the meta-analysis of ARIC and CHS was rs6933598 in methylenetetrahydrofolate dehydrogenase (P = 7.46 x 10(-05)) with a P value in FHS of 0.042. The top variants in FITS were rs12249562 in cubulin (P = 3.03 x 10(-05)) and rs9839267 near chole-cystoldnin (P = 3.05 x 10(-05)) with a P value of 0.019 for rs9839267 in CHS. We have here shown feasibility in evaluating lifetime incidence of heavy alcohol drinking from population-based studies for the purpose of conducting genetic association analyses.
C1 [Hamidovic, Ajna; Spring, Bonnie; Hitsman, Brian] Northwestern Univ, Chicago, IL 60611 USA.
[Goodloe, Robert J.; Jorgenson, Eric] Vanderbilt Univ, Med Ctr, Ctr Human Genet, Nashville, TN USA.
[Young, Taylor R.] SRI Int, Ctr Hlth Sci, Menlo Pk, CA 94025 USA.
[Styn, Mindi A.] Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, Pittsburgh, PA 15261 USA.
[Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Choquet, Helene; Kasberger, Jay L.] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, San Francisco, CA 94143 USA.
[Buxbaum, Sarah G.] Jackson State Univ, Jackson Heart Study, Jackson, MS USA.
[Papanicolaou, George J.] NHLBI, Div Cardiovasc Sci, Prevent & Populat Sci Program, Bethesda, MD 20892 USA.
[White, Wendy] Tougaloo Coll, Nat Sci Div, Tougaloo, MS USA.
[Volcik, Kelly] Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Human Genet Ctr, Houston, TX USA.
[Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Hamidovic, A (reprint author), Northwestern Univ, 680 N Lakeshore Dr,Suite 1400, Chicago, IL 60611 USA.
EM a-hamidovic@northwestern.edu
RI Buxbaum, Sarah/E-1970-2013
OI Buxbaum, Sarah/0000-0002-4886-3564
FU MD Scientist Fellowship in Genetic Medicine (Northerstern Memorial
Foundation); National Research Service Award (NIH/NIDA) [F32DA024920];
Dr. Bonnie Spring's Professional Account at Northwestern Feinberg School
of Medicine; NIAAA [R21 AA021223-01]; National Heart, Lung and Blood
Institute; NHLBI [HHSN268200960009C]
FX All sources of support: MD Scientist Fellowship in Genetic Medicine
(Northerstern Memorial Foundation; PI: A. Hamidovic), National Research
Service Award F32DA024920 (NIH/NIDA; PI: A. Hamidovic), Dr. Bonnie
Spring's Professional Account at Northwestern Feinberg School of
Medicine, NIAAA R21 AA021223-01, E. Jorgenson). The Candidate gene
Association Resource (CARe) wishes to acknowledge the support of the
National Heart, Lung and Blood Institute and the contributions of the
research institutions, study investigators, field staff and study
participants in creating this resource for biomedical research (NHLBI
contract number HHSN268200960009C). The following eight parent studies
have contributed parent study data, ancillary study data, and DNA
samples through the Broad Institute (N01-HC-65226) to create this
genotype/phenotype database for wide dissemination to the biomedical
research community: the Atherosclerosis Risk in Communities (ARK) study,
the CHS, the Cleveland Family Study (CFS), the Coronary Artery Risk
Development in Young Adults (CARDIA) study, the Framingham Heart Study,
the Jackson Heart Study (JHS), the Multi-Ethnic Study of Atherosclerosis
(MESA), and the Sleep Heart Health Study (SHHS). Individual study
funding attributions can be obtained at
http://public.nhlbi.nih.gov/GeneticsGenomics/home/care.aspx.
NR 53
TC 0
Z9 0
U1 0
U2 15
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0271-0749
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD APR
PY 2013
VL 33
IS 2
BP 206
EP 210
DI 10.1097/JCP.0b013e318287009a
PG 5
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA 108NX
UT WOS:000316303700010
PM 23422394
ER
PT J
AU Ferrer, RA
Portnoy, DB
Klein, WMP
AF Ferrer, Rebecca A.
Portnoy, David B.
Klein, William M. P.
TI Worry and Risk Perceptions as Independent and Interacting Predictors of
Health Protective Behaviors
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID BREAST-CANCER RISK; PHYSICAL-ACTIVITY; PERCEIVED RISK; BELIEF MODEL;
METAANALYSIS; PREVENTION; COMMUNICATION; INFORMATION; VACCINATION;
INTENTIONS
AB Worry and risk perceptions are generally found to be independently associated with health-promoting behaviors, although it is unknown whether they interact in ways that potentially dampen the effect of either construct on behavior. In this hypothesis-generating study, cancer-related worry and risk perception, and their interaction, were used to predict odds of meeting 5-a-day fruit and vegetable consumption guidelines and engaging in any exercise using data from a nationally representative sample (N=10,230). Risk perception was not associated with either behavior; worry was associated only with exercise (OR=1.77, 95% CI: 1.16, 2.70, p<.01). More important, their interaction was associated with these behaviors in a counterintuitive manner; among those higher in worry, higher levels of risk perception were associated with lower vegetable consumption (OR=0.79, 95% CI: 0.62, 1.00, p<.05) and exercise (OR=0.77, 95% CI: 0.63, 0.95, p=.01). These results suggest the hypothesis that, among people high in worry, attempts to increase risk perception could be counterproductive. These and related findings suggest the importance of distinguishing worry from risk perception, and future research is necessary to determine the causal nature of these associations.
C1 [Ferrer, Rebecca A.; Portnoy, David B.; Klein, William M. P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, NIH, Rockville, MD 20852 USA.
[Portnoy, David B.] NIH, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
RP Ferrer, RA (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 4089A, Rockville, MD 20852 USA.
EM ferrerra@mail.nih.gov
OI Portnoy, David/0000-0003-2175-9457
NR 50
TC 16
Z9 16
U1 1
U2 19
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1081-0730
EI 1087-0415
J9 J HEALTH COMMUN
JI J. Health Commun.
PD APR 1
PY 2013
VL 18
IS 4
BP 397
EP 409
DI 10.1080/10810730.2012.727954
PG 13
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA 109RV
UT WOS:000316387100004
PM 23272708
ER
PT J
AU Puntervoll, HE
Yang, XHR
Vetti, HH
Bachmann, IM
Avril, MF
Benfodda, M
Catricala, C
Dalle, S
Duval-Modeste, AB
Ghiorzo, P
Grammatico, P
Harland, M
Hayward, NK
Hu, HH
Jouary, T
Martin-Denavit, T
Ozola, A
Palmer, JM
Pastorino, L
Pjanova, D
Soufir, N
Steine, SJ
Stratigos, AJ
Thomas, L
Tinat, J
Tsao, H
Veinalde, R
Tucker, MA
Bressac-de Paillerets, BBD
Newton-Bishop, JA
Goldstein, AM
Akslen, LA
Molven, A
AF Puntervoll, Hanne Eknes
Yang, Xiaohong R.
Vetti, Hildegunn Hoberg
Bachmann, Ingeborg M.
Avril, Marie Francoise
Benfodda, Meriem
Catricala, Caterina
Dalle, Stephane
Duval-Modeste, Anne B.
Ghiorzo, Paola
Grammatico, Paola
Harland, Mark
Hayward, Nicholas K.
Hu, Hui-Han
Jouary, Thomas
Martin-Denavit, Tanguy
Ozola, Aija
Palmer, Jane M.
Pastorino, Lorenza
Pjanova, Dace
Soufir, Nadem
Steine, Solrun J.
Stratigos, Alexander J.
Thomas, Luc
Tinat, Julie
Tsao, Hensin
Veinalde, Ruta
Tucker, Margaret A.
Bressac-de Paillerets, Brigitte
Newton-Bishop, Julia A.
Goldstein, Alisa M.
Akslen, Lars A.
Molven, Anders
TI Melanoma prone families with CDK4 germline mutation: phenotypic profile
and associations with MC1R variants
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID 1 RECEPTOR MC1R; CDKN2A MUTATIONS; CUTANEOUS MELANOMA; RED HAIR;
MALIGNANT-MELANOMA; PANCREATIC-CANCER; DYSPLASTIC NEVI; INCREASED RISK;
ATYPICAL NEVI; GENE VARIANTS
AB Background CDKN2A and CDK4 are high risk susceptibility genes for cutaneous malignant melanoma. Melanoma families with CDKN2A germline mutations have been extensively characterised, whereas CDK4 families are rare and lack a systematic investigation of their phenotype.
Methods All known families with CDK4 germline mutations (n=17) were recruited for the study by contacting the authors of published papers or by requests via the Melanoma Genetics Consortium (GenoMEL). Phenotypic data related to primary melanoma and pigmentation characteristics were collected. The CDK4 exon 2 and the complete coding region of the MC1R gene were sequenced.
Results Eleven families carried the CDK4 R24H mutation whereas six families had the R24C mutation. The total number of subjects with verified melanoma was 103, with a median age at first melanoma diagnosis of 39 years. Forty-three (41.7%) subjects had developed multiple primary melanomas (MPM). A CDK4 mutation was found in 89 (including 62 melanoma cases) of 209 tested subjects. CDK4 positive family members (both melanoma cases and unaffected subjects) were more likely to have clinically atypical nevi than CDK4 negative family members (p<0.001). MPM subjects had a higher frequency of MC1R red hair colour variants compared with subjects with one tumour (p=0.010).
Conclusion Our study shows that families with CDK4 germline mutations cannot be distinguished phenotypically from CDKN2A melanoma families, which are characterised by early onset of disease, increased occurrence of clinically atypical nevi, and development of MPM. In a clinical setting, the CDK4 gene should therefore always be examined when a melanoma family tests negative for CDKN2A mutation.
C1 [Puntervoll, Hanne Eknes; Bachmann, Ingeborg M.; Steine, Solrun J.; Akslen, Lars A.; Molven, Anders] Univ Bergen, Sect Pathol, Gade Inst, N-5021 Bergen, Norway.
[Yang, Xiaohong R.; Tucker, Margaret A.; Goldstein, Alisa M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Vetti, Hildegunn Hoberg] Haukeland Hosp, Ctr Med Genet & Mol Med, Western Norway Familial Canc Ctr, N-5021 Bergen, Norway.
[Bachmann, Ingeborg M.] Haukeland Hosp, Dept Dermatol, N-5021 Bergen, Norway.
[Avril, Marie Francoise] Univ Paris 05, Hop Cochin Tarnier, AP HP, Paris, France.
[Benfodda, Meriem; Hu, Hui-Han; Soufir, Nadem] Univ Paris 07, St Louis Hosp, AP HP, Dept Genet,Bichat Hosp, Paris, France.
[Benfodda, Meriem; Hu, Hui-Han; Soufir, Nadem] Univ Paris 07, INSERM, St Louis Hosp, Cutaneous Res Ctr,U976, Paris, France.
[Catricala, Caterina] IRCCS, San Gallicano Dermatol Inst, Dept Dermatol Oncol, Rome, Italy.
[Dalle, Stephane; Martin-Denavit, Tanguy; Thomas, Luc] Univ Lyon 1, Hosp Civils Lyon, Ctr Hosp Lyon Sud, Unit Dermatol, F-69365 Lyon, France.
[Duval-Modeste, Anne B.] Rouen Univ Hosp, Dept Dermatol, Rouen, France.
[Ghiorzo, Paola; Pastorino, Lorenza] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy.
[Ghiorzo, Paola; Pastorino, Lorenza] San Martino IST Res Hosp, Lab Genet Rare Hereditary Canc, Genoa, Italy.
[Grammatico, Paola] Univ Roma La Sapienza, Dept Mol Med, S Camillo Forlanini Hosp, Rome, Italy.
[Harland, Mark; Newton-Bishop, Julia A.] St James Univ Hosp, Leeds Canc Res UK Ctr, Leeds Inst Mol Med, Epidemiol & Biostat Sect, Leeds, W Yorkshire, England.
[Hayward, Nicholas K.; Palmer, Jane M.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Jouary, Thomas] Serv Dermatol, Unite Cancerol Cutanee, Bordeaux, France.
[Ozola, Aija; Pjanova, Dace; Veinalde, Ruta] Latvian Biomed Res & Study Ctr, Riga, Latvia.
[Stratigos, Alexander J.] Univ Athens, Sch Med, Andreas Sygros Hosp, Dept Dermatol,Dermatooncol Unit, GR-11527 Athens, Greece.
[Tinat, Julie] Rouen Univ Hosp, Dept Genet, Rouen, France.
[Tsao, Hensin] Massachusetts Gen Hosp, MGH Canc Ctr, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, Serv Genet, Dept Biopathol, Villejuif, France.
[Bressac-de Paillerets, Brigitte] Fdn Jean Dausset, INSERM, U946, Paris, France.
[Akslen, Lars A.] Univ Bergen, Ctr Canc Biomarkers, Gade Inst, N-5021 Bergen, Norway.
[Akslen, Lars A.; Molven, Anders] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway.
RP Molven, A (reprint author), Univ Bergen, Haukeland Univ Hosp, Gade Inst, Sect Pathol, N-5021 Bergen, Norway.
EM anders.molven@gades.uib.no
RI Tucker, Margaret/B-4297-2015; hayward, nicholas/C-1367-2015; Akslen,
Lars /C-1202-2017;
OI hayward, nicholas/0000-0003-4760-1033; Akslen, Lars
/0000-0003-2710-9543; Newton Bishop, Julia/0000-0001-9147-6802;
Veinalde, Ruta/0000-0001-9190-5574
FU European Commission [LSHC-CT-2006-018702]; Cancer Research UK
[C588/A4994, C588/A10589, C8216/A6129]; US National Institutes of Health
(NIH) [CA83115]; University of Bergen; INSERM Research Fellowship; INCA;
Norwegian Cancer Society [71512-PR-2006-0356]; Intramural Research
Program of the NIH, National Cancer Institute, Division of Cancer
Epidemiology and Genetics; Leeds Cancer Research UK Centre
[C37059/A11941]; Latvian Council of Science [10.0010.8]; National Health
and Medical Research Council of Australia; Italian Ministry of Health;
PRIN; Sapienza University of Rome; Institut National du Cancer PHRC [AOM
07, 195, N107004]; Lyon 1 University; Hospices Civils de Lyon; Ligue
Contre le Cancer du Rhone; NIH [K24 CA149202]
FX The GenoMEL study was funded by the European Commission under the 6th
Framework Programme (contract no. LSHC-CT-2006-018702), by Cancer
Research UK Programme Awards (C588/A4994 and C588/A10589), by a Cancer
Research UK Project grant (C8216/A6129), and by a grant from the US
National Institutes of Health (NIH; CA83115). This research was also
supported by a PhD fellowship from the University of Bergen to HEP, an
INSERM Research Fellowship for hospital based scientists and an INCA
coordinator or grant to BB-de P, and grants from the following sources:
Norwegian Cancer Society (71512-PR-2006-0356); Intramural Research
Program of the NIH, National Cancer Institute, Division of Cancer
Epidemiology and Genetics; Leeds Cancer Research UK Centre
(C37059/A11941); Latvian Council of Science (No. 10.0010.8); National
Health and Medical Research Council of Australia; Italian Ministry of
Health; PRIN 2008; Sapienza University of Rome; Institut National du
Cancer PHRC 2007 (AOM 07, 195, N107004); Lyon 1 University; Hospices
Civils de Lyon; Ligue Contre le Cancer du Rhone; and NIH (K24 CA149202).
NR 41
TC 38
Z9 39
U1 3
U2 15
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
J9 J MED GENET
JI J. Med. Genet.
PD APR
PY 2013
VL 50
IS 4
BP 264
EP U82
DI 10.1136/jmedgenet-2012-101455
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 106AW
UT WOS:000316114800008
PM 23384855
ER
PT J
AU Song, JH
Fang, ZZ
Zhu, LL
Cao, YF
Hu, CM
Ge, GB
Zhao, DW
AF Song, Jin-Hui
Fang, Zhong-Ze
Zhu, Liang-Liang
Cao, Yun-Feng
Hu, Cui-Min
Ge, Guang-Bo
Zhao, De-Wei
TI Glucuronidation of the broad-spectrum antiviral drug arbidol by UGT
isoforms
SO JOURNAL OF PHARMACY AND PHARMACOLOGY
LA English
DT Article
DE arbidol; glucuronidation; UDP-glucuronosyltransferases (UGTs)
ID HUMAN UDP-GLUCURONOSYLTRANSFERASES; MYCOPHENOLIC-ACID; HUMAN LIVER;
IN-VITRO; GENETIC POLYMORPHISMS; VIRUS; PHARMACOKINETICS;
IDENTIFICATION; METABOLISM; BIOACTIVATION
AB Objectives The aim of this work was to identify the uridine glucuronosyltransferase (UGT) isoforms involved in the metabolism of the broad-spectrum antiviral drug arbidol. Methods A human liver microsome (HLM) incubation system was employed to catalyse the formation of arbidol glucuronide. The glucuronidation activity of commercially recombinant UGT isoforms towards arbidol was screened. A combination of kinetic analysis and chemical inhibition study was used to determine the UGT isoforms involved in arbidol's glucuronidation. Key findings The arbidol glucuronide was detected when arbidol was incubated with HLMs in the presence of UDP-glucuronic acid. The EadieHofstee plot showed that glucuronidation of arbidol was best fit to the MichaelisMenten kinetic model, and Km and apparent Vmax were calculated to be 8.0 +/- 0.7m and 2.03 +/- 0.05nmol/min/mg protein, respectively. Assessment of a panel of recombinant UGT isoforms revealed that UGT1A1, UGT1A3 and UGT1A9 could catalyse the glucuronidation of arbidol. Kinetic analysis and chemical inhibition study demonstrated that UGT1A9 was the predominant UGT isoform involved in arbidol glucuronidation in HLMs. Conclusions The major contribution of UGT1A9 towards arbidol glucuronidation was demonstrated in this study.
C1 [Song, Jin-Hui; Zhao, De-Wei] Dalian Univ, Affiliated Zhongshan Hosp, Dept Orthoped, Dalian 116001, Peoples R China.
[Fang, Zhong-Ze] Liaoning Med Univ, Jinzhou, Peoples R China.
[Cao, Yun-Feng] Shanghai Inst Planned Parenthood Res, Shanghai Engineer & Technol Res Ctr Reprod Hlth D, Key Lab Contracept & Devices Res NPFPC, Shanghai, Peoples R China.
[Zhu, Liang-Liang; Ge, Guang-Bo] Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China.
[Fang, Zhong-Ze; Hu, Cui-Min] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Zhao, DW (reprint author), Dalian Univ, Affiliated Zhongshan Hosp, Dept Orthoped, Dalian 116001, Peoples R China.
EM zhaodewei2000@163.com
FU National Key Technology RD Program [2012BAI7B02]; National Science &
Technology Major Project of China [2012ZX09501001, 2012ZX09506001,
2012ZX10002011]; National Natural Science Foundation of China [81202586,
81001473, 81273590]
FX This work was supported by the National Key Technology R&D Program
(2012BAI7B02), the National Science & Technology Major Project of China
(2012ZX09501001, 2012ZX09506001 & 2012ZX10002011), and the National
Natural Science Foundation of China (81202586, 81001473 & 81273590).
NR 36
TC 19
Z9 19
U1 0
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3573
EI 2042-7158
J9 J PHARM PHARMACOL
JI J. Pharm. Pharmacol.
PD APR
PY 2013
VL 65
IS 4
BP 521
EP 527
DI 10.1111/jphp.12014
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 108KO
UT WOS:000316292000006
PM 23488780
ER
PT J
AU Gill, JM
Saligan, L
Lee, H
Rotolo, S
Szanton, S
AF Gill, Jessica M.
Saligan, Leorey
Lee, Henna
Rotolo, Susan
Szanton, Sarah
TI Women in recovery from PTSD have similar inflammation and quality of
life as non-traumatized controls
SO JOURNAL OF PSYCHOSOMATIC RESEARCH
LA English
DT Article
DE Health; Inflammation; Resilience; Trauma; Women
ID POSTTRAUMATIC-STRESS-DISORDER; HEALTH-CARE UTILIZATION; ALPHA-INDUCED
CHANGES; INTERFERON-ALPHA; METABOLIC SYNDROME; PSYCHOMETRIC PROPERTIES;
DEPRESSIVE SYMPTOMS; VIETNAM VETERANS; HEART-DISEASE; WAR VETERANS
AB Objective: Post-traumatic stress disorder (PTSD) is associated with greater concentrations of inflammatory biomarkers as well as substantial medical burden; however, it is not clear if these morbidity risks change following recovery from PTSD. In this study we compare women who have-recovered from PTSD, to those with current PTSD, and healthy controls on their perceived health and inflammatory and metabolic biomarkers.
Methods: We studied 3 groups of women: those with current PTSD, those who reported recovery from PTSD, and healthy non-traumatized controls, which were determined using standard diagnostic instruments. We obtained a morning blood sample and examined concentrations of inflammatory biomarkers of: interleukin 6 (IL-6) and c-reactive protein (CRP), and lipid concentrations. Lastly, we evaluated health related quality of life (HRQOL).
Results: Women who had recovered from PTSD had a similar HRQOL and inflammatory biomarkers as non-traumatized controls. Their concentrations of inflammatory biomarkers were lower than women with current PTSD, and similar to non-traumatized controls.
Conclusion: Health perception as well as biological indicators of health significantly differ in women in recovery from PTSD, compared to those who remain symptomatic. These findings suggest that the psychological recovery is associated with normal levels of inflammatory biomarkers and HRQOL. (C) 2012 Published by Elsevier Inc.
C1 [Gill, Jessica M.; Saligan, Leorey; Lee, Henna] NINR, NIH, Bethesda, MD 20892 USA.
[Gill, Jessica M.] George Mason Univ, Sch Nursing, Fairfax, VA 22030 USA.
[Rotolo, Susan] Inova Hlth Serv, Falls Church, VA USA.
[Szanton, Sarah] Johns Hopkins Univ, Sch Nursing, Baltimore, MD 21218 USA.
RP Gill, JM (reprint author), 10 Ctr Dr, Bethesda, MD 20892 USA.
EM gillj@mail.nih.gov
NR 86
TC 15
Z9 15
U1 7
U2 21
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3999
EI 1879-1360
J9 J PSYCHOSOM RES
JI J. Psychosomat. Res.
PD APR
PY 2013
VL 74
IS 4
BP 301
EP 306
DI 10.1016/j.jpsychores.2012.10.013
PG 6
WC Psychiatry
SC Psychiatry
GA 112IT
UT WOS:000316586600006
PM 23497831
ER
PT J
AU Borkenau, P
McCrae, RR
Terracciano, A
AF Borkenau, Peter
McCrae, Robert R.
Terracciano, Antonio
TI Do men vary more than women in personality? A study in 51 cultures
SO JOURNAL OF RESEARCH IN PERSONALITY
LA English
DT Article
DE Cross-cultural research; Individualism; Multilevel modeling; Sex
differences; Variability
ID SEX-DIFFERENCES; GENDER-DIFFERENCES; VARIABILITY; TRAITS; METAANALYSIS;
FEMALES; MALES
AB Do men vary more than women in personality? Evolutionary, genetic, and cultural arguments suggest that hypothesis. In this study we tested it using 12,156 college student raters from 51 cultures who described a person they knew well on the 3rd-person version of the Revised NEO Personality Inventory. In most cultures, male targets varied more than female targets, and ratings by female informants varied more than ratings by male informants, which may explain why higher variances for men are not found in self-reports. Variances were higher in more developed, and effects of target sex were stronger in more individualistic societies. It seems that individualistic cultures enable a less restricted expression of personality, resulting in larger variances and particularly so among men. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Borkenau, Peter] Univ Halle Wittenberg, Dept Psychol, D-06099 Halle, Germany.
[Terracciano, Antonio] Florida State Univ, Coll Med, Dept Geriatr, Tallahassee, FL 32306 USA.
[Terracciano, Antonio] NIA, Baltimore, MD 21224 USA.
RP Borkenau, P (reprint author), Univ Halle Wittenberg, Dept Psychol, D-06099 Halle, Germany.
EM p.borkenau@psych.uni-halle.de
RI terracciano, antonio/B-1884-2008
FU Intramural NIH HHS [Z99 AG999999, ZIA AG000180-25, ZIA AG000180-26]
NR 39
TC 6
Z9 6
U1 3
U2 31
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0092-6566
J9 J RES PERS
JI J. Res. Pers.
PD APR
PY 2013
VL 47
IS 2
BP 135
EP 144
DI 10.1016/j.jrp.2012.12.001
PG 10
WC Psychology, Social
SC Psychology
GA 111ND
UT WOS:000316527100001
PM 23559686
ER
PT J
AU Tiseo, M
Rajan, A
Thomas, A
Giaccone, G
AF Tiseo, Marcello
Rajan, Arun
Thomas, Anish
Giaccone, Giuseppe
TI "Pseudocavitation" in Thymic Carcinoma During Treatment with Sunitinib
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Editorial Material
C1 [Tiseo, Marcello; Rajan, Arun; Thomas, Anish; Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Giaccone, G (reprint author), NCI, Med Oncol Branch, 12N-226,10 Ctr Dr, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
RI Giaccone, Giuseppe/E-8297-2017;
OI Giaccone, Giuseppe/0000-0002-5023-7562; Thomas,
Anish/0000-0003-3293-3115
FU Intramural NIH HHS [Z01 BC010854-01]
NR 0
TC 1
Z9 1
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD APR
PY 2013
VL 8
IS 4
BP 511
EP 512
DI 10.1097/JTO.0b013e318284378f
PG 2
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 107HO
UT WOS:000316206600023
PM 23486269
ER
PT J
AU Brooks-Russell, A
Foshee, VA
Ennett, ST
AF Brooks-Russell, Ashley
Foshee, Vangie A.
Ennett, Susan T.
TI Predictors of Latent Trajectory Classes of Physical Dating Violence
Victimization
SO JOURNAL OF YOUTH AND ADOLESCENCE
LA English
DT Article
DE Adolescent dating violence; Physical victimization; Trajectories; Growth
mixture model
ID VARIABLE-CENTERED ANALYSES; ADOLESCENT SUBSTANCE USE;
HIGH-SCHOOL-STUDENTS; ALCOHOL-USE; HIGH-RISK; DEVELOPMENTAL
TRAJECTORIES; FEMALE ADOLESCENTS; GENDER-DIFFERENCES; PARTNER VIOLENCE;
ADULT OUTCOMES
AB This study identified classes of developmental trajectories of physical dating violence victimization from grades 8 to 12 and examined theoretically-based risk factors that distinguished among trajectory classes. Data were from a multi-wave longitudinal study spanning 8th through 12th grade (n = 2,566; 51.9 % female). Growth mixture models were used to identify trajectory classes of physical dating violence victimization separately for girls and boys. Logistic and multinomial logistic regressions were used to identify situational and target vulnerability factors associated with the trajectory classes. For girls, three trajectory classes were identified: a low/non-involved class; a moderate class where victimization increased slightly until the 10th grade and then decreased through the 12th grade; and a high class where victimization started at a higher level in the 8th grade, increased substantially until the 10th grade, and then decreased until the 12th grade. For males, two classes were identified: a low/non-involved class, and a victimized class where victimization increased slightly until the 9th grade, decreased until the 11th grade, and then increased again through the 12th grade. In bivariate analyses, almost all of the situational and target vulnerability risk factors distinguished the victimization classes from the non-involved classes. However, when all risk factors and control variables were in the model, alcohol use (a situational vulnerability) was the only factor that distinguished membership in the moderate trajectory class from the non-involved class for girls; anxiety and being victimized by peers (target vulnerability factors) were the factors that distinguished the high from the non-involved classes for the girls; and victimization by peers was the only factor distinguishing the victimized from the non-involved class for boys. These findings contribute to our understanding of the heterogeneity in physical dating violence victimization during adolescence and the malleable risk factors associated with each trajectory class for boys and girls.
C1 [Brooks-Russell, Ashley] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
[Foshee, Vangie A.; Ennett, Susan T.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Behav, Chapel Hill, NC USA.
RP Brooks-Russell, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd Room 7B13, Bethesda, MD 20892 USA.
EM ashley.russell@nih.gov
RI Brooks-Russell, Ashley/F-8364-2014
OI Brooks-Russell, Ashley/0000-0002-7728-8423
FU NIDA NIH HHS [R01 DA013459, R01DA16669]; PHS HHS [R49CCV423114]
NR 77
TC 17
Z9 17
U1 1
U2 15
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0047-2891
J9 J YOUTH ADOLESCENCE
JI J. Youth Adolesc.
PD APR
PY 2013
VL 42
IS 4
SI SI
BP 566
EP 580
DI 10.1007/s10964-012-9876-2
PG 15
WC Psychology, Developmental
SC Psychology
GA 107GF
UT WOS:000316202400007
PM 23212350
ER
PT J
AU Crane, FL
Navas, P
Low, H
Sun, IL
de Cabo, R
AF Crane, Frederick L.
Navas, Placido
Low, Hans
Sun, Iris L.
de Cabo, Rafael
TI Sirtuin Activation: A Role for Plasma Membrane in the Cell Growth Puzzle
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Transplasma membrane; electron transport system; RedOx; Sirtuin; NAD;
Cell growth
ID ELECTRON-TRANSPORT; REDOX SYSTEM; EMBRYONIC FIBROBLASTS; UP-REGULATION;
HL-60 CELLS; LIFE-SPAN; NADH; TRANSFERRIN; INHIBITION; STRESS
AB For more than 20 years, the observation that impermeable oxidants can stimulate cell growth has not been satisfactorily explained. The discovery of sirtuins provides a logical answer to the puzzle. The NADH-dependent transplasma membrane electron transport system, which is stimulated by growth factors and interventions such as calorie restriction, can transfer electrons to external acceptors and protect against stress-induced apoptosis. We hypothesize that the activation of plasma membrane electron transport contributes to the cytosolic NAD pool required for sirtuin to activate transcription factors necessary for cell growth and survival.
C1 [Crane, Frederick L.; Low, Hans] Purdue Univ, Dept Biol, W Lafayette, IN 47907 USA.
[Navas, Placido] Karolinska Inst, Dept Mol Med, Stockholm, Sweden.
[Sun, Iris L.] Univ Pablo de Olavide, CSIC, Inst Salud Carlos III, CIBERER,CABD, Seville 41013, Spain.
[de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
RP de Cabo, R (reprint author), NIA, Lab Expt Gerontol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM deCaboRa@grc.nia.nih.gov
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU Spanish Ministerio de Sanidad (FIS) [PI11/00078]; National Institutes of
Health (NIH) [1R01AG028125-01A1]; Intramural Research Program of the
NIA/NIH
FX We would like to acknowledge financial support from Spanish Ministerio
de Sanidad (FIS; grant PI11/00078), National Institutes of Health (NIH;
grant 1R01AG028125-01A1), and the Intramural Research Program of the
NIA/NIH.
NR 31
TC 4
Z9 4
U1 0
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD APR
PY 2013
VL 68
IS 4
BP 368
EP 370
DI 10.1093/gerona/gls184
PG 3
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 108DX
UT WOS:000316273000004
PM 23033342
ER
PT J
AU Coen, PM
Jubrias, SA
Distefano, G
Amati, F
Mackey, DC
Glynn, NW
Manini, TM
Wohlgemuth, SE
Leeuwenburgh, C
Cummings, SR
Newman, AB
Ferrucci, L
Toledo, FGS
Shankland, E
Conley, KE
Goodpaster, BH
AF Coen, Paul M.
Jubrias, Sharon A.
Distefano, Giovanna
Amati, Francesca
Mackey, Dawn C.
Glynn, Nancy W.
Manini, Todd M.
Wohlgemuth, Stephanie E.
Leeuwenburgh, Christiaan
Cummings, Steven R.
Newman, Anne B.
Ferrucci, Luigi
Toledo, Frederico G. S.
Shankland, Eric
Conley, Kevin E.
Goodpaster, Bret H.
TI Skeletal Muscle Mitochondrial Energetics Are Associated With Maximal
Aerobic Capacity and Walking Speed in Older Adults
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Muscle; Mitochondria; Aging; Walking speed
ID PHYSICAL PERFORMANCE-MEASURES; LOWER-EXTREMITY FUNCTION; IN-VIVO;
OXIDATIVE CAPACITY; CELLULAR ENERGETICS; BODY-COMPOSITION; GAIT
PARAMETERS; MASS; AGE; EFFICIENCY
AB Lower ambulatory performance with aging may be related to a reduced oxidative capacity within skeletal muscle. This study examined the associations between skeletal muscle mitochondrial capacity and efficiency with walking performance in a group of older adults.
Thirty-seven older adults (mean age 78 years; 21 men and 16 women) completed an aerobic capacity (VO2 peak) test and measurement of preferred walking speed over 400 m. Maximal coupled (State 3; St3) mitochondrial respiration was determined by high-resolution respirometry in saponin-permeabilized myofibers obtained from percutanous biopsies of vastus lateralis (n = 22). Maximal phosphorylation capacity (ATP(max)) of vastus lateralis was determined in vivo by P-31 magnetic resonance spectroscopy (n = 30). Quadriceps contractile volume was determined by magnetic resonance imaging. Mitochondrial efficiency (max ATP production/max O-2 consumption) was characterized using ATP(max) per St3 respiration (ATP(max)/St3).
In vitro St3 respiration was significantly correlated with in vivo ATP(max) (r(2) = .47, p = .004). Total oxidative capacity of the quadriceps (St3*quadriceps contractile volume) was a determinant of VO2 peak (r(2) = .33, p = .006). ATP(max) (r(2) = .158, p = .03) and VO2 peak (r(2) = .475, p < .0001) were correlated with preferred walking speed. Inclusion of both ATP(max)/St3 and VO2 peak in a multiple linear regression model improved the prediction of preferred walking speed (r(2) = .647, p < .0001), suggesting that mitochondrial efficiency is an important determinant for preferred walking speed.
Lower mitochondrial capacity and efficiency were both associated with slower walking speed within a group of older participants with a wide range of function. In addition to aerobic capacity, lower mitochondrial capacity and efficiency likely play roles in slowing gait speed with age.
C1 [Coen, Paul M.] Univ Pittsburgh, Dept Hlth & Phys Act, Pittsburgh, PA 15260 USA.
[Coen, Paul M.; Distefano, Giovanna; Amati, Francesca; Toledo, Frederico G. S.; Goodpaster, Bret H.] Univ Pittsburgh, Div Endocrinol & Metab, Pittsburgh, PA 15260 USA.
[Jubrias, Sharon A.; Shankland, Eric; Conley, Kevin E.] Univ Washington, Med Ctr, Seattle, WA 98195 USA.
[Mackey, Dawn C.; Cummings, Steven R.] Calif Pacific Med Ctr Res Inst, San Francisco, CA USA.
[Glynn, Nancy W.; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Manini, Todd M.; Wohlgemuth, Stephanie E.; Leeuwenburgh, Christiaan] Univ Florida, Gainesville, FL USA.
[Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
RP Coen, PM (reprint author), Univ Pittsburgh, Dept Hlth & Phys Act, Trees Hall Rm 134D,Allequippa St & Darragh St, Pittsburgh, PA 15260 USA.
EM pmc17@pitt.edu
RI Toledo, Frederico/G-9071-2013; Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Amati, Francesca/0000-0002-1731-0262;
Coen, Paul/0000-0002-2805-2115; Glynn, Nancy/0000-0003-2265-0162
FU Pittsburgh Claude D. Pepper Older Americans Independence Center [P30
AG024827]; National Institute of Aging; ARRA funds [1RC2AG036594,
1RC2AG036606]; National Institute of Arthritis and Musculoskeletal and
Skin [R01 AR 41928]; National Center for Research Resources (NCRR) [UL1
RR024153]
FX The Study of Energy and Aging (SEA) Pilot was supported by the
Pittsburgh Claude D. Pepper Older Americans Independence Center (P30
AG024827), the National Institute of Aging, with ARRA funds
(1RC2AG036594, 1RC2AG036606), National Institute of Arthritis and
Musculoskeletal and Skin (R01 AR 41928), and by the National Center for
Research Resources (NCRR) (UL1 RR024153).
NR 41
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U1 3
U2 15
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD APR
PY 2013
VL 68
IS 4
BP 447
EP 455
DI 10.1093/gerona/gls196
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 108DX
UT WOS:000316273000015
PM 23051977
ER
PT J
AU White, DK
Neogi, T
Nevitt, MC
Peloquin, CE
Zhu, YY
Boudreau, RM
Cauley, JA
Ferrucci, L
Harris, TB
Satterfield, SM
Simonsick, EM
Strotmeyer, ES
Zhang, YQ
AF White, Daniel K.
Neogi, Tuhina
Nevitt, Michael C.
Peloquin, Christine E.
Zhu, Yanyan
Boudreau, Robert M.
Cauley, Jane A.
Ferrucci, Luigi
Harris, Tamara B.
Satterfield, Susan M.
Simonsick, Eleanor M.
Strotmeyer, Elsa S.
Zhang, Yuqing
TI Trajectories of Gait Speed Predict Mortality in Well-Functioning Older
Adults: The Health, Aging and Body Composition Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Gait speed; Older adults; Mortality
ID DWELLING ELDERLY-PEOPLE; PHYSICAL FUNCTION; WALKING SPEED;
MUSCULOSKELETAL PAIN; PERFORMANCE; AGE; METAANALYSIS; EXERCISE; WOMEN;
DISABILITY
AB Although gait speed slows with age, the rate of slowing varies greatly. To date, little is known about the trajectories of gait speed, their correlates, and their risk for mortality in older adults.
Gait speed during a 20-m walk was measured for a period of 8 years in initially well-functioning men and women aged 7079 years participating in the Health, Aging and Body Composition study. We described the trajectories of gait speed and examined their correlates using a group-based mixture model. Also risk associated with different gait speed trajectories on all-cause mortality was estimated using a Cox-proportional hazard model.
Of 2,364 participants (mean age, 73.52.9 years; 52% women), we identified three gait speed trajectories: slow (n 637), moderate (n 1,209), and fast decline (n 518). Those with fast decline slowed 0.030 m/s per year or 2.4% per year from baseline to the last follow-up visit. Women, blacks, and participants who were obese, had limited knee extensor strength, and had low physical activity were more likely to have fast decline than their counterparts. Participants with fast decline in gait speed had a 90% greater risk of mortality than those with slow decline.
Despite being well-functioning at baseline, a quarter of older adults experienced fast decline in gait speed, which was associated with an increased risk of mortality.
C1 [White, Daniel K.] Boston Univ, Dept Phys Therapy & Athlet Training, Coll Hlth & Rehabil Sci, Sargent Coll, Boston, MA 02215 USA.
[Neogi, Tuhina; Peloquin, Christine E.; Zhu, Yanyan; Zhang, Yuqing] Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02215 USA.
[Nevitt, Michael C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Boudreau, Robert M.; Cauley, Jane A.; Strotmeyer, Elsa S.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Ferrucci, Luigi; Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Satterfield, Susan M.] Univ Tennessee, Memphis, TN USA.
RP White, DK (reprint author), Boston Univ, Dept Phys Therapy & Athlet Training, Boston, MA 02215 USA.
EM dwtbn@bu.edu
RI Strotmeyer, Elsa/F-3015-2014;
OI Strotmeyer, Elsa/0000-0002-4093-6036; Boudreau,
Robert/0000-0003-0162-5187; Neogi, Tuhina/0000-0002-9515-1711; Cauley,
Jane A/0000-0003-0752-4408
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, R01-AG028050]; National Institute of Nursing Research
[R01-NR0124590]; Boston Claude D. Pepper Older Americans Independence
Center from the National Institutes on Aging [P30-AG031679]; Foundation
for Physical Therapy Geriatrics Research Grant; American College of
Rheumatology Research and Education Foundation Rheumatology Investigator
Award; National Institute of Arthritis and Musculoskeletal and Skin at
the National Institutes of Health [AR47785]; Intramural Research Program
of the NIH, National Institute on Aging
FX This work was supported by National Institute on Aging (NIA) (grant
numbers N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050) the
National Institute of Nursing Research (grant number R01-NR0124590; the
Boston Claude D. Pepper Older Americans Independence Center from the
National Institutes on Aging (grant number P30-AG031679); the Foundation
for Physical Therapy Geriatrics Research Grant; the American College of
Rheumatology Research and Education Foundation Rheumatology Investigator
Award; and the National Institute of Arthritis and Musculoskeletal and
Skin at the National Institutes of Health (grant number AR47785).; This
research was supported in part by the Intramural Research Program of the
NIH, National Institute on Aging.
NR 34
TC 42
Z9 43
U1 3
U2 29
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD APR
PY 2013
VL 68
IS 4
BP 456
EP 464
DI 10.1093/gerona/gls197
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 108DX
UT WOS:000316273000016
PM 23051974
ER
PT J
AU Thomas, A
Maltzman, J
Hassan, R
AF Thomas, Anish
Maltzman, Julia
Hassan, Raffit
TI Farletuzumab in lung cancer
SO LUNG CANCER
LA English
DT Review
DE Adenocarcinoma; Farletuzumab; Folate receptor alpha; Monoclonal
antibody; Non-small cell lung cancer; Immunohistochemistry
ID FOLATE-RECEPTOR-ALPHA; BINDING-PROTEIN; OVARIAN-CANCER;
MONOCLONAL-ANTIBODY; TARGETED THERAPY; NORMAL-TISSUES; EXPRESSION;
ADENOCARCINOMA; CHEMOTHERAPY; CARCINOMAS
AB Folate is essential for proliferating cells and folate transport pathways and folate-dependent metabolic processes show promise as targets for anti-neoplastic therapy. Folate receptor a (FOLR1), a folate transporter, is an attractive target for anti-neoplastic therapy due to its high affinity for folate, restricted range of expression in normal tissue and differential over-expression in malignant tissue. FOLR1 is expressed in non-small cell lung cancer, with a higher expression in adenocarcinoma compared with squamous cell carcinoma. Farletuzumab is a monoclonal antibody targeting FOLR1 which in pre-clinical studies led to cytotoxicity of FOLR1-expressing cells, inhibited tumor growth in animal models and showed limited reactivity with normal tissue. In phase I/II trials, farletuzumab was well tolerated as a single-agent and in combination, without additive toxicity with chemotherapy. An ongoing phase II, double blind, placebo-controlled study is evaluating farletuzumab in patients with FOLR1 expressing metastatic adenocarcinoma of lung. Published by Elsevier Ireland Ltd.
C1 [Thomas, Anish] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20814 USA.
[Maltzman, Julia] Morphotek, Exton, PA 19341 USA.
[Hassan, Raffit] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hassan, R (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5116, Bethesda, MD 20892 USA.
EM hassanr@mail.nih.gov
OI Thomas, Anish/0000-0003-3293-3115
FU NIH, National Cancer Institute, Center for Cancer Research; National
Cancer Institute; Morphotek
FX All authors contributed to data interpretation, manuscript development
and final approval of the manuscript for submission. RH is the guarantor
of the manuscript. This work was supported in part by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research and under a Cooperative Research and Development
Agreement between Morphotek and the National Cancer Institute.
NR 36
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Z9 13
U1 2
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-5002
J9 LUNG CANCER
JI Lung Cancer
PD APR
PY 2013
VL 80
IS 1
BP 15
EP 18
DI 10.1016/j.lungcan.2012.12.021
PG 4
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 112KH
UT WOS:000316590600003
PM 23357463
ER
PT J
AU Han, PKJ
Klabunde, CN
Noone, AM
Earle, CC
Ayanian, JZ
Ganz, PA
Virgo, KS
Potosky, AL
AF Han, Paul K. J.
Klabunde, Carrie N.
Noone, Anne-Michelle
Earle, Craig C.
Ayanian, John Z.
Ganz, Patricia A.
Virgo, Katherine S.
Potosky, Arnold L.
TI Physicians' Beliefs About Breast Cancer Surveillance Testing are
Consistent With Test Overuse
SO MEDICAL CARE
LA English
DT Article
DE breast cancer; survivorship care; surveillance; screening; overuse
ID PRIMARY-CARE-PHYSICIANS; FOLLOW-UP CARE; HEALTH-CARE; SURVIVORS;
QUALITY; COST; UNCERTAINTY; PERCEPTIONS; VIGNETTES; OVERUTILIZATION
AB Background: Overuse of surveillance testing for breast cancer survivors is an important problem but its extent and determinants are incompletely understood. The objectives of this study were to determine the extent to which physicians' breast cancer surveillance testing beliefs are consistent with test overuse, and to identify factors associated with these beliefs.
Methods: During 2009-2010, a cross-sectional survey of US medical oncologists and primary care physicians (PCPs) was carried out. Physicians responded to a clinical vignette ascertaining beliefs about appropriate breast cancer surveillance testing. Multivariable analyses examined the extent to which test beliefs were consistent with overuse and associated with physician and practice characteristics and physician perceptions, attitudes, and practices.
Results: A total of 1098 medical oncologists and 980 PCPs completed the survey (response rate 57.5%). Eighty-four percent of PCPs [95% confidence interval (CI), 81.4%-86.5%] and 72% of oncologists (95% CI, 69.8%-74.7%) reported beliefs consistent with blood test overuse, whereas 50% of PCPs (95% CI, 47.3%-53.8%) and 27% of oncologists (95% CI, 23.9%-29.3%) reported beliefs consistent with imaging test overuse. Among PCPs, factors associated with these beliefs included smaller practice size, lower patient volume, and practice ownership. Among oncologists, factors included older age, international medical graduate status, lower self-efficacy (confidence in knowledge), and greater perceptions of ambiguity (conflicting expert recommendations) regarding survivorship care.
Conclusions: Beliefs consistent with breast cancer surveillance test overuse are common, greater for PCPs and blood tests than for oncologists and imaging tests, and associated with practice characteristics and perceived self-efficacy and ambiguity about testing. These results suggest modifiable targets for efforts to reduce surveillance test overuse.
C1 [Han, Paul K. J.] Maine Med Ctr, Ctr Outcomes Res & Evaluat, Portland, ME 04101 USA.
[Han, Paul K. J.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Klabunde, Carrie N.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Noone, Anne-Michelle] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Earle, Craig C.] Ontario Inst Canc Res, Toronto, ON, Canada.
[Ayanian, John Z.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Hlth Care Policy,Div Gen Med, Boston, MA 02115 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Los Angeles, CA 90024 USA.
[Virgo, Katherine S.] Amer Canc Soc, Intramural Res Dept, Hlth Serv Res Program, Atlanta, GA 30329 USA.
[Potosky, Arnold L.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
RP Han, PKJ (reprint author), Maine Med Ctr, Ctr Outcomes Res & Evaluat, 590 Forest Ave,Suite 200, Portland, ME 04101 USA.
EM hanp@mmc.org
OI Han, Paul/0000-0003-0165-1940
FU National Cancer Institute [HSN261200700068C]; American Cancer Society
FX Support for the Survey of Physicians' Attitudes Regarding the Care of
Cancer Survivors (SPARCCS) was provided by the National Cancer Institute
(contract number HSN261200700068C) and the American Cancer Society
through its intramural research funds. P.K.J.H. had full access to all
of the data in the study and takes responsibility for the integrity of
the data and the accuracy of the data analysis.
NR 51
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U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7079
J9 MED CARE
JI Med. Care
PD APR
PY 2013
VL 51
IS 4
BP 315
EP 323
DI 10.1097/MLR.0b013e31827da908
PG 9
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 107HS
UT WOS:000316207100007
PM 23269111
ER
PT J
AU Mihara, T
Izumikawa, K
Kakeya, H
Ngamskulrungroj, P
Umeyama, T
Takazono, T
Tashiro, M
Nakamura, S
Imamura, Y
Miyazaki, T
Ohno, H
Yamamoto, Y
Yanagihara, K
Miyzaki, Y
Kohno, S
AF Mihara, Tomo
Izumikawa, Koichi
Kakeya, Hiroshi
Ngamskulrungroj, Popchai
Umeyama, Takashi
Takazono, Takahiro
Tashiro, Masato
Nakamura, Shigeki
Imamura, Yoshifumi
Miyazaki, Taiga
Ohno, Hideaki
Yamamoto, Yoshihiro
Yanagihara, Katsunori
Miyzaki, Yoshitsugu
Kohno, Shigeru
TI Multilocus sequence typing of Cryptococcus neoformans in non-HIV
associated cryptococcosis in Nagasaki, Japan
SO MEDICAL MYCOLOGY
LA English
DT Article
DE MLST; C. neoformans; Japan; ST 5; VNII
ID VAR. GRUBII SEROTYPE; SPECIES COMPLEX; MOLECULAR EPIDEMIOLOGY; GATTII;
DIVERSITY; VARIETIES; GENOTYPE; STRAINS; CHINA
AB Cryptococcosis is primarily caused by two Cryptococcus species, i.e., Cryptococcus neoformans and C. gattii. Both include several genetically diverse subgroups that can be differentiated using various molecular strain typing methods. Since little is known about the molecular epidemiology of the C. neoformans/C. gattii species complex in Japan, we conducted a molecular epidemiological analysis of 35 C. neoformans isolates from non-HIV patients in Nagasaki, Japan and 10 environmental isolates from Thailand. All were analyzed using URA5-restriction fragment length polymorphism (RFLP) and multilocus sequence typing (MLST). Combined sequence data for all isolates were evaluated with the neighbor-joining method. All were found to be serotype A and mating type MAT alpha. Thirty-two of the 35 clinical isolates molecular type VNI, while the three remaining isolates were VNII as determined through the URA5-RFLP method. Thirty-one of the VNI isolates were identified as MLST sequence type (ST) 5, the remaining one was ST 32 and the three VNII isolates were found to be ST 43. All the environmental isolates were identified as molecular type VNI (four MLST ST 5 and six ST 4). Our study shows that C. neoformans isolates in Nagasaki are genetically homogeneous, with most of the isolates being ST 5.
C1 [Mihara, Tomo; Izumikawa, Koichi; Kakeya, Hiroshi; Takazono, Takahiro; Tashiro, Masato; Nakamura, Shigeki; Imamura, Yoshifumi; Miyazaki, Taiga; Yamamoto, Yoshihiro; Kohno, Shigeru] Nagasaki Univ, Grad Sch Biomed Sci, Dept Mol Microbiol & Immunol, Nagasaki 8528501, Japan.
[Ngamskulrungroj, Popchai] NIAID, NIH, Bethesda, MD 20892 USA.
[Ngamskulrungroj, Popchai] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Microbiol, Bangkok 10700, Thailand.
[Umeyama, Takashi; Ohno, Hideaki; Miyzaki, Yoshitsugu] Natl Inst Infect Dis, Dept Chemotherapy & Mycoses, Tokyo, Japan.
[Yanagihara, Katsunori] Nagasaki Univ Hosp, Dept Lab Med, Nagasaki, Japan.
RP Izumikawa, K (reprint author), Nagasaki Univ, Grad Sch Biomed Sci Nagasaki, Dept Mol Microbiol & Immunol, 1-7-1 Sakamoto, Nagasaki 8528501, Japan.
EM koizumik@nagasaki-u.ac.jp
OI Umeyama, Takashi/0000-0002-6635-4288
FU Ministry of Health, Labour and Welfare of Japan [H23-shinkou-ippan-018]
FX This work was partly supported by a grant from the Ministry of Health,
Labour and Welfare of Japan (H23-shinkou-ippan-018). We thank Dr June
Kwon-Chung, National Institutes of Health, Bethesda, MD, USA, for her
advice and support, about the methods, manipulation and interpretation
of data, and for providing the Cryptococcus reference strains used in
this study. Also, we thank Assoc. Prof. Wieland Meyer and Dr Luciana
Trilles for their help with allele and sequence type designation.
NR 39
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U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1369-3786
J9 MED MYCOL
JI Med. Mycol.
PD APR
PY 2013
VL 51
IS 3
BP 252
EP 260
DI 10.3109/13693786.2012.708883
PG 9
WC Infectious Diseases; Mycology; Veterinary Sciences
SC Infectious Diseases; Mycology; Veterinary Sciences
GA 107OQ
UT WOS:000316228100004
PM 22901045
ER
PT J
AU Mason, C
Xiao, LR
Imayama, I
Duggan, CR
Foster-Schubert, KE
Kong, A
Campbell, KL
Wang, CY
Villasenor, A
Neuhouser, ML
Alfano, CM
Blackburn, GL
McTiernan, A
AF Mason, Caitlin
Xiao, Liren
Imayama, Ikuyo
Duggan, Catherine R.
Foster-Schubert, Karen E.
Kong, Angela
Campbell, Kristin L.
Wang, Ching-Yun
Villasenor, Adriana
Neuhouser, Marian L.
Alfano, Catherine M.
Blackburn, George L.
McTiernan, Anne
TI Influence of Diet, Exercise, and Serum Vitamin D on Sarcopenia in
Postmenopausal Women
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE CALORIC RESTRICTION; WEIGHT LOSS; 25-HYDROXYVITAMIN D; AGING
ID WEIGHT-LOSS; BODY-COMPOSITION; MUSCLE STRENGTH; D DEFICIENCY;
PHYSICAL-ACTIVITIES; OLDER PERSONS; ELDERLY-WOMEN; HIP FRACTURE; LEAN
MASS; BONE LOSS
AB MASON, C., L. XIAO, I. IMAYAMA, C. R. DUGGAN, K. E. FOSTER-SCHUBERT, A. KONG, K. L. CAMPBELL, C.-Y. WANG, A. VILLASENOR, M. L. NEUHOUSER, C. M. ALFANO, G. L. BLACKBURN, and A. MCTIERNAN. Influence of Diet, Exercise, and Serum Vitamin D on Sarcopenia in Postmenopausal Women. Med. Sci. Sports Exerc., Vol. 45, No. 4, pp. 607-614, 2013. Purpose: The objective of this study is to investigate the effects of 12 months of dietary weight loss and/or aerobic exercise on lean mass and the measurements defining sarcopenia in postmenopausal women and to examine the potential moderating effect of serum 25-hydroxyvitamin D (25(OH) D) and age. Methods: Four hundred thirty-nine overweight and obese postmenopausal women were randomized to diet modification (N = 118), exercise (N = 117), diet + exercise (N = 117), or control (N = 87). The diet intervention was a group-based program with a 10% weight loss goal. The exercise intervention was 45 min.d(-1), 5 d.wk(-1), of moderate-to-vigorous intensity aerobic activity. Total and appendicular lean mass (ALM) were quantified by dual x-ray absorptiometry at baseline and 12 months. A skeletal muscle index (SMI = ALM (kg) /height (m(2))) and the prevalence of sarcopenia (SMI <5.67 kg.m(-2)) were calculated. Serum 25(OH) D was assayed using a competitive chemiluminescent immunoassay. Results: Dietary weight loss resulted in a significant decrease in lean mass and a borderline significant decrease in ALM and SMI compared with controls. In contrast, aerobic exercise significantly preserved ALM and SMI. Diet + exercise attenuated the loss of ALM and SMI compared with diet alone and did not result in significant loss of total mass or ALM compared with controls. Neither serum 25(OH) D nor age was significant moderators of the intervention effects. Conclusions: Aerobic exercise added to dietary weight loss can attenuate the loss of ALM during weight loss and may be effective for the prevention and treatment of sarcopenia among overweight and obese postmenopausal women.
C1 [Mason, Caitlin; Xiao, Liren; Imayama, Ikuyo; Duggan, Catherine R.; Wang, Ching-Yun; Villasenor, Adriana; Neuhouser, Marian L.; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Foster-Schubert, Karen E.; Wang, Ching-Yun; Neuhouser, Marian L.; McTiernan, Anne] Univ Washington, Seattle, WA 98195 USA.
[Kong, Angela] Univ Illinois, Chicago, IL USA.
[Campbell, Kristin L.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA.
[Blackburn, George L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Nutr, Boston, MA 02215 USA.
[Alfano, Catherine M.] Ohio State Univ, Columbus, OH 43210 USA.
[Alfano, Catherine M.] NCI, Bethesda, MD 20892 USA.
RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, Prevent Ctr, M4-B874,POB 19024, Seattle, WA 98109 USA.
EM amctiern@fhcrc.org
RI Duggan, Catherine/F-9414-2015; Biguzzi, Felipe/E-4724-2015
OI Duggan, Catherine/0000-0001-7369-4021;
FU NIH [R01 CA102504, U54-CA116847, 5KL2RR025015-03]; Canadian Institutes
of Health Research (CIHR); NCI [R25 CA094880, 2R25CA057699-16]
FX This study was funded through NIH R01 CA102504 and U54-CA116847. CM and
KLC were supported by fellowships from the Canadian Institutes of Health
Research (CIHR).; KFS received support from NIH 5KL2RR025015-03.; AK was
supported by NCI R25 CA094880 and is now supported by NCI
2R25CA057699-16.
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U1 1
U2 39
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD APR
PY 2013
VL 45
IS 4
BP 607
EP 614
DI 10.1249/MSS.0b013e31827aa3fa
PG 8
WC Sport Sciences
SC Sport Sciences
GA 109ZK
UT WOS:000316410600001
PM 23190588
ER
PT J
AU Jin, GL
Mizutani, A
Fukuda, T
Otani, T
Yan, T
Vila, MP
Murakami, H
Kudoh, T
Hirohata, S
Kasai, T
Salomon, DS
Seno, M
AF Jin, Guoliang
Mizutani, Akifumi
Fukuda, Takayuki
Otani, Takayuki
Yan, Ting
Vila, Marta Prieto
Murakami, Hiroshi
Kudoh, Takayuki
Hirohata, Satoshi
Kasai, Tomonari
Salomon, David S.
Seno, Masaharu
TI Eosinophil cationic protein enhances stabilization of beta-catenin
during cardiomyocyte differentiation in P19CL6 embryonal carcinoma cells
SO MOLECULAR BIOLOGY REPORTS
LA English
DT Article
DE Eosinophil cationic protein; Cardiomyocyte differentiation; P19CL6
cells; Wnt signaling
ID WNT SIGNALING PATHWAY; WNT/BETA-CATENIN; CARDIAC DIFFERENTIATION;
TRANSCRIPTION FACTORS; PROGENITOR CELLS; STEM-CELLS; EXPRESSION;
INHIBITION; ACTIVATION; DISEASE
AB Prior to gastrulation, the Wnt signaling pathway through stabilized beta-catenin enhances the differentiation of mouse ES cell into cardiomyocytes. We have recently shown that cardiomyocyte differentiation is enhanced by eosinophil cationic protein (ECP) through accelerated expression of marker genes of early cardiac differentiation. Furthermore, ECP enhanced the expression of Wnt3a in P19CL6 cells which were stimulated to differentiate into cardiomyocytes by DMSO. Following these findings, we evaluated in this study the potential of ECP to activate the Wnt/beta-catenin signaling pathway during cardiomyocyte differentiation. Analysis by real time qPCR revealed that ECP increased the expression of Frizzled genes such as Frizzled-1, -2, -4 and -10 in P19CL6 cells in the presence of DMSO. The increased expression of those Wnt receptors was found to inhibit the phosphorylation of beta-catenin resulting in the stabilization and translocation of beta-catenin into the nucleus of P19CL6 cells during the early stages of cardiomyocyte differentiation. When assessed for beta-catenin/TCF transcriptional activity with a TCF-luciferase (TOP/FOP) assay, ECP enhanced luciferase activity in P19CL6 cells during 48 h after transfection with TOP/FOP flash reporter in a stoichiometric manner. Collectively, this suggests that ECP can activate a canonical Wnt/beta-catenin signaling pathway by enhancing the stabilization of beta-catenin during cardiomyocyte differentiation.
C1 [Jin, Guoliang; Mizutani, Akifumi; Fukuda, Takayuki; Otani, Takayuki; Yan, Ting; Vila, Marta Prieto; Murakami, Hiroshi; Kudoh, Takayuki; Kasai, Tomonari; Seno, Masaharu] Okayama Univ, Grad Sch Nat Sci & Technol, Dept Chem & Biotechnol, Lab Nanobiotechnol, Okayama 7008530, Japan.
[Jin, Guoliang] Xuzhou Med Coll, Affiliated Hosp, Dept Neurol, Xuzhou 221002, Jiangsu, Peoples R China.
[Hirohata, Satoshi] Okayama Univ, Grad Sch Med Dent & Pharmacol, Dept Mol Biol & Biochem, Okayama 7008558, Japan.
[Salomon, David S.] NCI, Lab Canc Prevent, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Seno, M (reprint author), Okayama Univ, Grad Sch Nat Sci & Technol, Dept Chem & Biotechnol, Lab Nanobiotechnol, Okayama 7008530, Japan.
EM mseno@cc.okayama-u.ac.jp
RI Hirohata, Satoshi/B-2253-2011; SENO, Masaharu /B-2092-2011
OI Hirohata, Satoshi/0000-0002-4815-5891; SENO, Masaharu
/0000-0001-8547-6259
FU Ministry of Education, Culture, Sports, Science and Technology; Japan
Science and Technology Agency (JST); Chugoku Industrial Innovation
Center
FX This research was supported in part by the Ministry of Education,
Culture, Sports, Science and Technology Grant-in-Aid for Scientific
Research, by Japan Science and Technology Agency (JST), and by Chugoku
Industrial Innovation Center.
NR 28
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U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0301-4851
EI 1573-4978
J9 MOL BIOL REP
JI Mol. Biol. Rep.
PD APR
PY 2013
VL 40
IS 4
BP 3165
EP 3171
DI 10.1007/s11033-012-2390-5
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 107MH
UT WOS:000316221100044
PM 23271121
ER
PT J
AU Sullivan, PF
Daly, MJ
Ripke, S
Lewis, CM
Lin, DY
Wray, NR
Neale, B
Levinson, DF
Breen, G
Byrne, EM
Wray, NR
Levinson, DF
Rietschel, M
Hoogendijk, W
Ripke, S
Sullivan, PF
Hamilton, SP
Levinson, DF
Lewis, CM
Ripke, S
Weissman, MM
Wray, NR
Breuer, R
Cichon, S
Degenhardt, F
Frank, J
Gross, M
Herms, S
Hoefels, S
Maier, W
Mattheisen, M
Noethen, MM
Rietschel, M
Schulze, TG
Steffens, M
Treutlein, J
Boomsma, DI
De Geus, EJ
Hoogendijk, W
Hottenga, JJ
Jung-Ying, T
Lin, DY
Middeldorp, CM
Nolen, WA
Penninx, BP
Smit, JH
Sullivan, PF
van Grootheest, G
Willemsen, G
Zitman, FG
Coryell, WH
Knowles, JA
Lawson, WB
Levinson, DF
Potash, JB
Scheftner, WA
Shi, JX
Weissman, MM
Holsboer, F
Muglia, P
Tozzi, F
Blackwood, DHR
Boomsma, DI
De Geus, EJ
Hottenga, JJ
MacIntyre, DJ
McIntosh, A
McLean, A
Middeldorp, CM
Nolen, WA
Penninx, BP
Ripke, S
Smit, JH
Sullivan, PF
van Grootheest, G
Willemsen, G
Zitman, FG
van den Oord, EJCG
Holsboer, F
Lucae, S
Binder, E
Muller-Myhsok, B
Ripke, S
Czamara, D
Kohli, MA
Ising, M
Uhr, M
Bettecken, T
Barnes, MR
Breen, G
Craig, IW
Farmer, AE
Lewis, CM
McGuffin, P
Muglia, P
Byrne, E
Gordon, SD
Heath, AC
Henders, AK
Hickie, IB
Madden, PAF
Martin, NG
Montgomery, GM
Nyholt, DR
Pergadia, ML
Wray, NR
Hamilton, SP
McGrath, PJ
Shyn, SI
Slager, SL
Oskarsson, H
Sigurdsson, E
Stefansson, H
Stefansson, K
Steinberg, S
Thorgeirsson, T
Levinson, DF
Potash, JB
Shi, JX
Weissman, MM
Guipponi, M
Lewis, G
O'Donovan, M
Tansey, KE
Uher, R
Coryell, WH
Knowles, JA
Lawson, WB
Levinson, DF
Potash, JB
Scheftner, WA
Shi, JX
Weissman, MM
Castro, VM
Churchill, SE
Fava, M
Gainer, VS
Gallagher, PJ
Goryachev, S
Iosifescu, DV
Kohane, IS
Murphy, SN
Perlis, RH
Smoller, JW
Weilburg, JB
Kutalik, Z
Preisig, M
Grabe, HJ
Nauck, M
Schulz, A
Teumer, A
Volzke, H
Landen, M
Lichtenstein, P
Magnusson, P
Pedersen, N
Viktorin, A
AF Sullivan, Patrick F.
Daly, Mark J.
Ripke, Stephan
Lewis, Cathryn M.
Lin, Dan-Yu
Wray, Naomi R.
Neale, Benjamin
Levinson, Douglas F.
Breen, Gerome
Byrne, Enda M.
Wray, Naomi R.
Levinson, Douglas F.
Rietschel, Marcella
Hoogendijk, Witte
Ripke, Stephan
Sullivan, Patrick F.
Hamilton, Steven P.
Levinson, Douglas F.
Lewis, Cathryn M.
Ripke, Stephan
Weissman, Myrna M.
Wray, Naomi R.
Breuer, Rene
Cichon, Sven
Degenhardt, Franziska
Frank, Josef
Gross, Magdalena
Herms, Stefan
Hoefels, Susanne
Maier, Wolfgang
Mattheisen, Manuel
Noeethen, Markus M.
Rietschel, Marcella
Schulze, Thomas G.
Steffens, Michael
Treutlein, Jens
Boomsma, Dorret I.
De Geus, Eco J.
Hoogendijk, Witte
Hottenga, Jouke Jan
Jung-Ying, Tzeng
Lin, Dan-Yu
Middeldorp, Christel M.
Nolen, Willem A.
Penninx, Brenda P.
Smit, Johannes H.
Sullivan, Patrick F.
van Grootheest, Gerard
Willemsen, Gonneke
Zitman, Frans G.
Coryell, William H.
Knowles, James A.
Lawson, William B.
Levinson, Douglas F.
Potash, James B.
Scheftner, William A.
Shi, Jianxin
Weissman, Myrna M.
Holsboer, Florian
Muglia, Pierandrea
Tozzi, Federica
Blackwood, Douglas H. R.
Boomsma, Dorret I.
De Geus, Eco J.
Hottenga, Jouke Jan
MacIntyre, Donald J.
McIntosh, Andrew
McLean, Alan
Middeldorp, Christel M.
Nolen, Willem A.
Penninx, Brenda P.
Ripke, Stephan
Smit, Johannes H.
Sullivan, Patrick F.
van Grootheest, Gerard
Willemsen, Gonneke
Zitman, Frans G.
van den Oord, Edwin J. C. G.
Holsboer, Florian
Lucae, Susanne
Binder, Elisabeth
Mueller-Myhsok, Bertram
Ripke, Stephan
Czamara, Darina
Kohli, Martin A.
Ising, Marcus
Uhr, Manfred
Bettecken, Thomas
Barnes, Michael R.
Breen, Gerome
Craig, Ian W.
Farmer, Anne E.
Lewis, Cathryn M.
McGuffin, Peter
Muglia, Pierandrea
Byrne, Enda
Gordon, Scott D.
Heath, Andrew C.
Henders, Anjali K.
Hickie, Ian B.
Madden, Pamela A. F.
Martin, Nicholas G.
Montgomery, Grant M.
Nyholt, Dale R.
Pergadia, Michele L.
Wray, Naomi R.
Hamilton, Steven P.
McGrath, Patrick J.
Shyn, Stanley I.
Slager, Susan L.
Oskarsson, Hoegni
Sigurdsson, Engilbert
Stefansson, Hreinn
Stefansson, Kari
Steinberg, Stacy
Thorgeirsson, Thorgeir
Levinson, Douglas F.
Potash, James B.
Shi, Jianxin
Weissman, Myrna M.
Guipponi, Michel
Lewis, Glyn
O'Donovan, Michael
Tansey, Katherine E.
Uher, Rudolf
Coryell, William H.
Knowles, James A.
Lawson, William B.
Levinson, Douglas F.
Potash, James B.
Scheftner, William A.
Shi, Jianxin
Weissman, Myrna M.
Castro, Victor M.
Churchill, Susanne E.
Fava, Maurizio
Gainer, Vivian S.
Gallagher, Patience J.
Goryachev, Sergey
Iosifescu, Dan V.
Kohane, Isaac S.
Murphy, Shawn N.
Perlis, Roy H.
Smoller, Jordan W.
Weilburg, Jeffrey B.
Kutalik, Zoltan
Preisig, Martin
Grabe, Hans J.
Nauck, Matthias
Schulz, Andrea
Teumer, Alexander
Voelzke, Henry
Landen, Mikael
Lichtenstein, Paul
Magnusson, Patrik
Pedersen, Nancy
Viktorin, Alexander
CA Psychiat GWAS Consortium
TI A mega-analysis of genome-wide association studies for major depressive
disorder
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE genetics; genome-wide association study; major depressive disorder;
mega-analysis; meta-analysis
ID CARDIOVASCULAR RISK-FACTORS; NATIONAL COMORBIDITY SURVEY; SEROTONIN
TRANSPORTER GENE; BIPOLAR DISORDER; SUSCEPTIBILITY LOCI;
PSYCHIATRIC-DISORDERS; MENTAL-DISORDERS; MOOD DISORDERS; TWIN REGISTRY;
HUMAN HEIGHT
AB Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5x10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9x10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status. Molecular Psychiatry (2013) 18, 497-511; doi:10.1038/mp.2012.21; published online 3 April 2012
C1 [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Daly, Mark J.; Ripke, Stephan] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA.
[Wray, Naomi R.] Univ Queensland, Queensland Inst Med Res, Brisbane, Qld 4072, Australia.
[Lewis, Cathryn M.; Breen, Gerome; Craig, Ian W.; Farmer, Anne E.; McGuffin, Peter; Tansey, Katherine E.; Uher, Rudolf] Kings Coll London, Inst Psychiat, London, England.
[Hamilton, Steven P.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Weissman, Myrna M.; McGrath, Patrick J.] Columbia Univ, New York, NY 10027 USA.
[Blackwood, Douglas H. R.; MacIntyre, Donald J.; McIntosh, Andrew; McLean, Alan] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland.
[Boomsma, Dorret I.; De Geus, Eco J.; Hottenga, Jouke Jan; Middeldorp, Christel M.; Willemsen, Gonneke] Vrije Univ Amsterdam, Amsterdam, Netherlands.
[Cichon, Sven; Degenhardt, Franziska; Gross, Magdalena; Herms, Stefan; Hoefels, Susanne; Maier, Wolfgang; Mattheisen, Manuel; Noeethen, Markus M.; Steffens, Michael] Univ Bonn, Bonn, Germany.
[Heath, Andrew C.; Madden, Pamela A. F.; Pergadia, Michele L.] Washington Univ, St Louis, MO USA.
[Byrne, Enda M.; Gordon, Scott D.; Henders, Anjali K.; Martin, Nicholas G.; Montgomery, Grant M.; Nyholt, Dale R.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Penninx, Brenda P.; Smit, Johannes H.; van Grootheest, Gerard] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
[Coryell, William H.; Potash, James B.] Univ Iowa, Iowa City, IA 52242 USA.
[Rietschel, Marcella; Breuer, Rene; Frank, Josef; Treutlein, Jens] Heidelberg Univ, Cent Inst Mental Hlth, Heidelberg, Germany.
[Sullivan, Patrick F.; Lin, Dan-Yu] Univ N Carolina, Chapel Hill, NC 27515 USA.
[Shi, Jianxin] NCI, Bethesda, MD 20892 USA.
[Grabe, Hans J.; Nauck, Matthias; Schulz, Andrea; Teumer, Alexander; Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany.
[Lichtenstein, Paul; Magnusson, Patrik; Pedersen, Nancy; Viktorin, Alexander] Karolinska Inst, S-10401 Stockholm, Sweden.
[Fava, Maurizio; Gallagher, Patience J.; Iosifescu, Dan V.; Murphy, Shawn N.; Smoller, Jordan W.; Weilburg, Jeffrey B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kutalik, Zoltan] Univ Lausanne, CH-1015 Lausanne, Switzerland.
[O'Donovan, Michael] Cardiff Univ, Cardiff CF10 3AX, S Glam, Wales.
[Guipponi, Michel] Univ Geneva, CH-1211 Geneva 4, Switzerland.
[Hickie, Ian B.] Univ Sydney, Sydney, NSW 2006, Australia.
Univ Birmingham, Birmingham B15 2TT, W Midlands, England.
[Jung-Ying, Tzeng] N Carolina State Univ, Raleigh, NC 27695 USA.
[Knowles, James A.] Univ So Calif, Los Angeles, CA 90089 USA.
[Kohane, Isaac S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
Queen Mary Univ London, London, England.
[Lawson, William B.] Howard Univ, Washington, DC USA.
[Lewis, Glyn] Univ Bristol, Bristol BS8 1TH, Avon, England.
Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England.
[Nolen, Willem A.] Univ Groningen, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands.
[Scheftner, William A.] Rush Univ, Med Ctr, Chicago, IL USA.
[Shyn, Stanley I.] Univ Washington, Seattle, WA 98195 USA.
[Slager, Susan L.] Mayo Clin, Rochester, MN 55905 USA.
[van den Oord, Edwin J. C. G.] Virginia Commonwealth Univ, Richmond, VA 23284 USA.
[Zitman, Frans G.] Leiden Univ, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Levinson, Douglas F.] Stanford Univ, Stanford, CA 94305 USA.
RP Sullivan, PF (reprint author), Univ N Carolina, Dept Genet, CB 7264, Chapel Hill, NC 27599 USA.
EM pfsulliv@med.unc.edu
RI Lewis, Glyn/E-9944-2012; Breen, Gerome/A-5540-2010; Wray,
Naomi/C-8639-2015; Mattheisen, Manuel/B-4949-2012; Magnusson,
Patrik/C-4458-2017; Schulze, Thomas/H-2157-2013; Nolen,
Willem/E-9006-2014; McGrath, Patrick/I-6410-2013; Lewis,
Cathryn/A-5225-2010; Tansey, Katherine/B-1033-2013; McGuffin,
Peter/A-1565-2012; McIntosh, Andrew/B-9379-2008; Uher,
Rudolf/A-5477-2008; Colaus, PsyColaus/K-6607-2013; Cichon,
Sven/H-8803-2013; Cichon, Sven/B-9618-2014; van Grootheest,
Gerard/C-6942-2014; Sigurdsson, Engilbert/D-2486-2014;
OI Lewis, Glyn/0000-0001-5205-8245; Breen, Gerome/0000-0003-2053-1792;
Wray, Naomi/0000-0001-7421-3357; Mattheisen, Manuel/0000-0002-8442-493X;
MacIntyre, Donald J/0000-0001-6963-1335; Hamilton,
Steven/0000-0001-8106-6260; Craig, Ian/0000-0002-4063-1005; McGrath,
Patrick/0000-0001-7217-7321; Lewis, Cathryn/0000-0002-8249-8476; Tansey,
Katherine/0000-0002-9663-3376; McGuffin, Peter/0000-0002-9888-2907;
McIntosh, Andrew/0000-0002-0198-4588; Uher, Rudolf/0000-0002-2998-0546;
Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; van
Grootheest, Gerard/0000-0003-4350-6661; Sigurdsson,
Engilbert/0000-0001-9404-7982; de Geus, Eco/0000-0001-6022-2666; Landen,
Mikael/0000-0002-4496-6451; lichtenstein, paul/0000-0003-3037-5287;
Viktorin, Alexander/0000-0003-2141-2816; Stefansson,
Hreinn/0000-0002-9331-6666; Nothen, Markus/0000-0002-8770-2464;
Middeldorp, Christel/0000-0002-6218-0428; Thorgeirsson,
Thorgeir/0000-0002-5149-7040
FU NIMH [MH085520, MH080403, MH061686, MH059542, MH075131, MH059552,
MH059541, MH060912, MH086026, MH081802, MH072802, N01MH90003]; German
Federal Ministry of Education and Research; National Genome Research
Network 2 (NGFN-2); National Genome Research Network plus (NGFNplus);
Integrated Genome Research Network (IG) MooDS [01GS08144, 01GS08147];
European Union [LSHM-CT-2006-037761, PIAP-GA-2008-218251,
HEALTH-F2-2009-223423]; Medical Research Council (UK); Mental Health
Research Network; Innovative Medicines Initiative [115008]; National
Alliance for Research on Schizophrenia and Depression; i2b2 Center
(Informatics for Integrating Biology and the Bedside); NIH
[U54LM008748]; BMBF Program Molecular Diagnostics: Validation of
Biomarkers for Diagnosis and Outcome in Major Depression [01ES0811];
Netherlands Organization for Scientific Research (MagW/ZonMW)
[904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, 912-100-20,
56-464-14192, 10-000-1002]; Center for Medical Systems Biology (NWO
Genomics); Biobanking and Biomolecular Resources Research
Infrastructure; VU University's Institutes for Health and Care Research
and Neuroscience Campus Amsterdam; NBIC/BioAssist/RK [2008.024];
European Science Foundation [EU/QLRT-2001-01254]; European Community;
ENGAGE [HEALTH-F4-2007-201413]; European Science Council (ERC) [230374];
Genetic Association Information Network (GAIN) of the Foundation for the
US National Institutes of Health; GAIN; Netherlands Organization for
Scientific Research (NOW-VENI grant) [916-76-125]; Swiss National
Science Foundation [3200B0-105993, 3200B0-118'308, 33CSC0-122661];
GlaxoSmithKline (Psychiatry Center of Excellence for Drug Discovery and
Genetics Division, Drug Discovery - Verona, RD); Australian National
Health; Medical Research Council [241944, 339462, 389927, 389875,
389891, 389892, 389938, 442915, 442981, 496675, 496739, 552485, 552498,
613602, 613608, 613674, 619667]; Australian Research Council [FT0991360,
FT0991022]; FP-5 GenomEUtwin Project [QLG2-CT-2002-01254]; US National
Institutes of Health [AA07535, AA10248, AA13320, AA13321, AA13326,
AA14041, MH66206, DA12854, DA019951, U01 DK066134]; Center for Inherited
Disease Research (Baltimore, MD, USA); UK Medical Research Council;
GlaxoSmithKline [G0701420]; National Institute for Health Research
(NIHR) Specialist Biomedical Research Centre for Mental Health at the
South London; Maudsley NHS Foundation Trust; Institute of Psychiatry,
King's College London; UK Medical Research Council [G0000647]; European
Commission [LSHB-CT-2003-503428]; Federal Ministry of Education and
Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; Ministry of Cultural
Affairs; Social Ministry of the Federal State of Mecklenburg-West
Pomerania; Federal Ministry of Education and Research; Siemens
Healthcare, Erlangen, Germany; Federal State of Mecklenburg-West
Pomerania; German Research Foundation [DFG: GR 1912/5-1]; Swedish
Ministry for Higher Education; Swedish Research Council [M-2005-1112];
GenomEUtwin [EU/QLRT-2001-01254, QLG2-CT-2002-01254]; Swedish Foundation
for Strategic Research; Wellcome Trust [076113, 085475]; [U54
RR020278]; [RC2MH089916]
FX We thank the thousands of people with MDD who donated time and effort to
make this research possible. The PGC was funded by NIMH Grants MH085520
(lead PI PFS) and MH080403. We thank our colleagues in the PGC Bipolar
Disorder Working Group who allowed pre-publication access to their GWAS
mega-analysis results for the MDD-BIP cross-disorder analyses. The
Bonn/Mannheim (BoMa) GWAS was supported by the German Federal Ministry
of Education and Research, within the context of the National Genome
Research Network 2 (NGFN-2), the National Genome Research Network plus
(NGFNplus) and the Integrated Genome Research Network (IG) MooDS (Grant
01GS08144 to S Cichon and MM Noethen, and Grant 01GS08147 to M
Rietschel). The work at deCODE was funded by European Union Grants
LSHM-CT-2006-037761 (Project SGENE), PIAP-GA-2008-218251 (Project
PsychGene) and HEALTH-F2-2009-223423 (Project PsychCNVs). GenPod was
funded by the Medical Research Council (UK) and supported by the Mental
Health Research Network. Genotyping of the GenPod sample was funded by
the Innovative Medicines Initiative Joint Undertaking under Grant
Agreement number 115008 (NEWMEDS). The GenRED GWAS project was supported
by NIMH R01 Grants MH061686 (DF Levinson), MH059542 (WH Coryell),
MH075131 (WB Lawson), MH059552 (JB Potash), MH059541 (WA Scheftner) and
MH060912 (MM Weissman). We acknowledge the contributions of Dr George S
Zubenko and Dr Wendy N Zubenko, Department of Psychiatry, University of
Pittsburgh School of Medicine, to the GenRED I project. The NIMH Cell
Repository at Rutgers University and the NIMH Center for Collaborative
Genetic Studies on Mental Disorders made essential contributions to this
project. Genotyping was carried out by the Broad Institute Center for
Genotyping and Analysis with support from Grant U54 RR020278 (which
partially subsidized the genotyping of the GenRED cases). Collection and
quality control analyses of the control data set were supported by
grants from NIMH and the National Alliance for Research on Schizophrenia
and Depression. We are grateful to Knowledge Networks (Menlo Park, CA,
USA) for assistance in collecting the control data set. We express our
profound appreciation to the families who participated in this project,
and to the many clinicians who facilitated the referral of participants
to the study. The Depression Genes and Networks ARRA grant was funded by
RC2MH089916. Funding for the Harvard i2b2 sample was provided by a
subcontract to RH Perlis and JW Smoller as part of the i2b2 Center
(Informatics for Integrating Biology and the Bedside), an NIH-funded
National Center for Biomedical Computing based at Partners HealthCare
System (U54LM008748, PI: IS Kohane), and by an NIMH Grant to RH Perlis
(MH086026). Max Planck Institute of Psychiatry MARS study was supported
by the BMBF Program Molecular Diagnostics: Validation of Biomarkers for
Diagnosis and Outcome in Major Depression (01ES0811). Genotyping was
supported by the Bavarian Ministry of Commerce, and the Federal Ministry
of Education and Research (BMBF) in the framework of the National Genome
Research Network (NGFN2 and NGFN-Plus, FKZ 01GS0481 and 01GS08145). The
Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands
Twin Register (NTR) contributed to GAIN-MDD and to MDD2000.; Funding was
from: the Netherlands Organization for Scientific Research (MagW/ZonMW
Grants 904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717,
912-100-20; Spinozapremie 56-464-14192; Geestkracht program Grant
10-000-1002); the Center for Medical Systems Biology (NWO Genomics),
Biobanking and Biomolecular Resources Research Infrastructure, VU
University's Institutes for Health and Care Research and Neuroscience
Campus Amsterdam, NBIC/BioAssist/RK (2008.024); the European Science
Foundation (EU/QLRT-2001-01254); the European Community's Seventh
Framework Program (FP7/2007-2013); ENGAGE (HEALTH-F4-2007-201413); and
the European Science Council (ERC, 230374). Genotyping was funded in
part by the Genetic Association Information Network (GAIN) of the
Foundation for the US National Institutes of Health, and analysis was
supported by grants from GAIN and the NIMH (MH081802). CM Middeldorp was
supported by the Netherlands Organization for Scientific Research
(NOW-VENI grant 916-76-125). The PsyCoLaus study was supported by grants
from the Swiss National Science Foundation (#3200B0-105993,
#3200B0-118'308, 33CSC0-122661) and from GlaxoSmithKline (Psychiatry
Center of Excellence for Drug Discovery and Genetics Division, Drug
Discovery - Verona, R&D). We express our gratitude to the Lausanne
inhabitants who volunteered to participate in the PsyCoLaus study. We
also thank V Mooser, G Weaber and P Vollenweider who initiated the
CoLaus project. Funding for the QIMR samples was provided by the
Australian National Health and Medical Research Council (241944, 339462,
389927, 389875, 389891, 389892, 389938, 442915, 442981, 496675, 496739,
552485, 552498, 613602, 613608, 613674, 619667), the Australian Research
Council (FT0991360, FT0991022), the FP-5 GenomEUtwin Project
(QLG2-CT-2002-01254) and the US National Institutes of Health (AA07535,
AA10248, AA13320, AA13321, AA13326, AA14041, MH66206, DA12854,
DA019951), and the Center for Inherited Disease Research (Baltimore, MD,
USA). We thank the twins and their families registered at the Australian
Twin Registry for their participation in the many studies that have
contributed to this research. RADIANT was funded by: a joint grant from
the UK Medical Research Council and GlaxoSmithKline (G0701420); the
National Institute for Health Research (NIHR) Specialist Biomedical
Research Centre for Mental Health at the South London and Maudsley NHS
Foundation Trust and the Institute of Psychiatry, King's College London;
and the UK Medical Research Council (G0000647). The GENDEP study was
funded by a European Commission Framework 6 grant, EC Contract Ref.:
LSHB-CT-2003-503428. SHIP is part of the Community Medicine Research net
of the University of Greifswald, Germany, which is funded by the Federal
Ministry of Education and Research (Grants no. 01ZZ9603, 01ZZ0103 and
01ZZ0403), the Ministry of Cultural Affairs and the Social Ministry of
the Federal State of Mecklenburg-West Pomerania. Genome-wide data have
been supported by the Federal Ministry of Education and Research (Grant
no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen,
Germany and the Federal State of Mecklenburg-West Pomerania. The
University of Greifswald is a member of the 'Center of Knowledge
Interchange' program of the Siemens AG. SHIP-LEGEND is funded by the
German Research Foundation (DFG: GR 1912/5-1). Genotyping of
STARstarD was supported by an NIMH Grant to SP Hamilton
(MH072802).; STARstarD was funded by the National Institute
of Mental Health (contract N01MH90003) to the University of Texas
Southwestern Medical Center at Dallas (AJ Rush, principal investigator).
The TwinGene study was supported by the Swedish Ministry for Higher
Education, the Swedish Research Council (M-2005-1112), GenomEUtwin
(EU/QLRT-2001-01254; QLG2-CT-2002-01254), the Swedish Foundation for
Strategic Research and the US National Institutes of Health (U01
DK066134). This study makes use of data generated by the Wellcome Trust
Case-Control Consortium. A full list of the investigators who
contributed to the generation of the data is available from
http://www.wtccc.org.uk. Funding for the project was provided by the
Wellcome Trust under awards 076113 and 085475.
NR 87
TC 105
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U1 13
U2 119
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 APR
PY 2013
VL 18
IS 4
BP 497
EP 511
DI 10.1038/mp.2012.21
PG 15
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 112CE
UT WOS:000316568600016
ER
PT J
AU Abbas, AK
Benoist, C
Bluestone, JA
Campbell, DJ
Ghosh, S
Hori, S
Jiang, SP
Kuchroo, VK
Mathis, D
Roncarolo, MG
Rudensky, A
Sakaguchi, S
Shevach, EM
Vignali, DAA
Ziegler, SF
AF Abbas, Abul K.
Benoist, Christophe
Bluestone, Jeffrey A.
Campbell, Daniel J.
Ghosh, Sankar
Hori, Shohei
Jiang, Shuiping
Kuchroo, Vijay K.
Mathis, Diane
Roncarolo, Maria Grazia
Rudensky, Alexander
Sakaguchi, Shimon
Shevach, Ethan M.
Vignali, Dario A. A.
Ziegler, Steve F.
TI Regulatory T cells: recommendations to simplify the nomenclature
SO NATURE IMMUNOLOGY
LA English
DT Letter
C1 [Abbas, Abul K.] Univ Calif San Francisco, Sch Med, Dept Pathol, San Francisco, CA 94143 USA.
[Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA USA.
[Bluestone, Jeffrey A.] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
[Campbell, Daniel J.; Ziegler, Steve F.] Benaroya Res Inst, Immunol Program, Seattle, WA USA.
[Ghosh, Sankar] Columbia Univ Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA.
[Hori, Shohei] RIKEN Res Ctr Allergy & Immunol, Res Unit Immune Homeostasis, Yokohama, Kanagawa, Japan.
[Jiang, Shuiping] Immunis Clin, Beijing, Peoples R China.
[Kuchroo, Vijay K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA.
[Roncarolo, Maria Grazia] Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, Div Regenerat Med Stem Cells & Gene Therapy, I-20132 Milan, Italy.
[Rudensky, Alexander] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10021 USA.
[Sakaguchi, Shimon] Osaka Univ, World Premier Initiat Immunol Frontier Res Ctr, Expt Immunol Lab, Osaka, Japan.
[Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Vignali, Dario A. A.] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA.
RP Abbas, AK (reprint author), Univ Calif San Francisco, Sch Med, Dept Pathol, San Francisco, CA 94143 USA.
EM dario.vignali@stjude.org
RI Sakaguchi, Shimon/C-9535-2009;
OI RONCAROLO, Maria Grazia/0000-0002-2193-9186
FU Telethon [TGT11E01]
NR 0
TC 176
Z9 183
U1 4
U2 28
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 APR
PY 2013
VL 14
IS 4
BP 307
EP 308
PG 2
WC Immunology
SC Immunology
GA 113EG
UT WOS:000316648700001
PM 23507634
ER
PT J
AU Bell, BD
Kitajima, M
Larson, RP
Stoklasek, TA
Pang, K
Sakamoto, K
Wagner, KU
Reizis, B
Hennighausen, L
Ziegler, SF
AF Bell, Bryan D.
Kitajima, Masayuki
Larson, Ryan P.
Stoklasek, Thomas A.
Pang, Kristen
Sakamoto, Kazuhito
Wagner, Kay-Uwe
Reizis, Boris
Hennighausen, Lothar
Ziegler, Steven F.
TI The transcription factor STAT5 is critical in dendritic cells for the
development of T(H)2 but not T(H)1 responses
SO NATURE IMMUNOLOGY
LA English
DT Article
ID THYMIC STROMAL LYMPHOPOIETIN; MEDIATED SIGNAL-TRANSDUCTION;
ATOPIC-DERMATITIS; T-CELLS; FLUORESCEIN ISOTHIOCYANATE; CONTACT
HYPERSENSITIVITY; IMMUNE-RESPONSES; TSLP; INFLAMMATION; SKIN
AB Dendritic cells (DCs) are critical in immune responses, linking innate and adaptive immunity. We found here that DC-specific deletion of the transcription factor STAT5 was not critical for development but was required for T helper type 2 (T(H)2), but not T(H)1, allergic responses in both the skin and lungs. Loss of STAT5 in DCs led to the inability to respond to thymic stromal lymphopoietin (TSLP). STAT5 was required for TSLP-dependent DC activation, including upregulation of the expression of costimulatory molecules and chemokine production. Furthermore, T(H)2 responses in mice with DC-specific loss of STAT5 resembled those seen in mice deficient in the receptor for TSLP. Our results show that the TSLP-STAT5 axis in DCs is a critical component for the promotion of type 2 immunity at barrier surfaces.
C1 [Bell, Bryan D.; Kitajima, Masayuki; Larson, Ryan P.; Stoklasek, Thomas A.; Pang, Kristen; Ziegler, Steven F.] Benaroya Res Inst Virginia Mason, Program Immunol, Seattle, WA USA.
[Bell, Bryan D.; Kitajima, Masayuki; Larson, Ryan P.; Stoklasek, Thomas A.; Ziegler, Steven F.] Univ Washington, Dept Immunol, Sch Med, Seattle, WA 98195 USA.
[Sakamoto, Kazuhito; Wagner, Kay-Uwe] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE USA.
[Reizis, Boris] Columbia Univ, Med Ctr, Dept Microbiol & Immunol, New York, NY USA.
[Hennighausen, Lothar] US Natl Inst Hlth, Lab Genet & Physiol, Bethesda, MD USA.
RP Ziegler, SF (reprint author), Benaroya Res Inst Virginia Mason, Program Immunol, Seattle, WA USA.
EM sziegler@benaroyaresearch.org
OI Reizis, Boris/0000-0003-1140-7853
FU US National Institutes of Health [R01-AI068731, R01-AR056113,
R01-AR055695, P01-HL098067, 5T32AI007411-19]
FX We thank D. Kaplan (University of Minnesota) for langerin-Cre mice; I.
Forster (University of Bonn) for mice with a transgene encoding GFP in
the Ccl17locus; T. Nakayama (Chiba University) for pMX-Cre-IRES-GFP; D.
Rawlings and H. Kerns (Seattle Children's Research Institute) for Btk-
and Tec-deficient bone marrow; J. Hamerman and D. Campbell for
discussions of the manuscript; S. Ma and W Xu for technical support; and
M. Warren and S. McCarty for administrative support. Supported by the US
National Institutes of Health (R01-AI068731, R01-AR056113, R01-AR055695
and P01-HL098067 to S.F.Z., and 5T32AI007411-19 to B.D.B.).
NR 40
TC 53
Z9 56
U1 3
U2 15
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 APR
PY 2013
VL 14
IS 4
BP 364
EP 371
DI 10.1038/ni.2541
PG 8
WC Immunology
SC Immunology
GA 113EG
UT WOS:000316648700011
PM 23435120
ER
PT J
AU Becerra, SP
Notario, V
AF Becerra, S. Patricia
Notario, Vicente
TI The effects of PEDF on cancer biology: mechanisms of action and
therapeutic potential
SO NATURE REVIEWS CANCER
LA English
DT Review
ID EPITHELIUM-DERIVED FACTOR; ENDOTHELIAL GROWTH-FACTOR; CEREBELLAR GRANULE
CELLS; ANTI-ANGIOGENIC ACTIVITY; ORTHOTOPIC OSTEOSARCOMA GROWTH; FACTOR
INHIBITS ANGIOGENESIS; ADIPOSE TRIGLYCERIDE LIPASE; RETINAL-PIGMENT
EPITHELIUM; MEDIATED GENE-TRANSFER; TUMOR-GROWTH
AB The potent actions of pigment epithelium-derived factor (PEDF) on tumour-associated cells, and its extracellular localization and secretion, stimulated research on this multifunctional serpin. Such studies have identified several PEDF receptors and downstream signalling pathways. Known cellular PEDF responses have expanded from the initial discovery that PEDF induces retinoblastoma cell differentiation to its anti-angiogenic, antitumorigenic and antimetastatic properties. Although the diversity of PEDF activities seems to be complex, they are consistent with the varied mechanisms that regulate this multimodal factor. If PEDF is to be used for cancer management, a deeper appreciation of its many functions and mechanisms of action is needed.
C1 [Becerra, S. Patricia] NEI, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Notario, Vicente] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
RP Becerra, SP (reprint author), NEI, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM becerrap@nei.nih.gov
FU US National Institutes of Health (NIH) [1ZIA-EY000306]; US National
Cancer Institute (NCI) [R01-CA134727]
FX This work was supported in part by the intramural research program of
the US National Institutes of Health (NIH) (Project number
1ZIA-EY000306) to S. P. B. and by grant R01-CA134727 from the US
National Cancer Institute (NCI) to V.N.
NR 178
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-175X
J9 NAT REV CANCER
JI Nat. Rev. Cancer
PD APR
PY 2013
VL 13
IS 4
BP 258
EP 271
DI 10.1038/nrc3484
PG 14
WC Oncology
SC Oncology
GA 111YH
UT WOS:000316557500013
PM 23486238
ER
PT J
AU Rangel, A
Race, B
Striebel, J
Chesebro, B
AF Rangel, A.
Race, B.
Striebel, J.
Chesebro, B.
TI Non-amyloid and amyloid prion protein deposits in prion-infected mice
differ in blockage of interstitial brain fluid
SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
LA English
DT Article
DE basement membrane; brain interstitial fluid; cerebral amyloid
angiopathy; glycophosphatidylinositol anchor; prion
ID 87V MURINE SCRAPIE; ALZHEIMERS-DISEASE; ANGIOPATHY; PATHOLOGY;
PATHOPHYSIOLOGY; DISORDERS; PHENOTYPE; PRNP
AB Aims Prion diseases are characterized by brain deposits of misfolded aggregated protease-resistant prion protein (PrP), termed PrPres. In humans and animals, PrPres is found as either disorganized non-amyloid aggregates or organized amyloid fibrils. Both PrPres forms are found in extracellular spaces of the brain. Thus, both might block drainage of brain interstitial fluid (ISF). The present experiments studied whether ISF blockage occurred during amyloid and/or non-amyloid prion diseases. Methods Various-sized fluorescein-labelled ISF tracers were stereotactically inoculated into the striatum of adult mice. At times from 5min to 77h, uninfected and scrapie-infected mice were compared. C57BL/10 mice expressing wild-type anchored PrP, which develop non-amyloid PrPres similar to humans with sporadic CreutzfeldtJakob disease, were compared with Tg44+/+ mice (transgenic mice secreting anchorless PrP) expressing anchorless PrP, which develop amyloid PrPres similar to certain human familial prion diseases. Results In C57BL/10 mice, extensive non-amyloid PrPres aggregate deposition was not associated with abnormal clearance kinetics of tracers. In contrast, scrapie-infected Tg44+/+ mice showed blockage of tracer clearance and colocalization of tracer with perivascular PrPres amyloid. Conclusions As tracer localization and clearance was normal in infected C57BL/10 mice, ISF blockage was not an important pathogenic mechanism in this model. Therefore, ISF blockage is unlikely to be a problem in non-amyloid human prion diseases such as sporadic CreutzfeldtJakob disease. In contrast, partial ISF blockage appeared to be a possible pathogenic mechanism in Tg44+/+ mice. Thus this mechanism might also influence human amyloid prion diseases where expression of anchorless or mutated PrP results in perivascular amyloid PrPres deposition and cerebral amyloid angiopathy.
C1 [Rangel, A.; Race, B.; Striebel, J.; Chesebro, B.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA.
RP Chesebro, B (reprint author), NIAID, Rocky Mt Labs, 903 South 4th St, Hamilton, MT 59840 USA.
EM bchesebro@nih.gov
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX The authors thank Dan Long, Lori Lubke and Nancy Kurtz for histological
technical support. We also thank Drs Martin Jeffrey and Suzette Priola
for calling our attention to previous studies of the ISF system, Drs
Suzette Priola, Byron Caughey and John Portis for critical evaluation of
the manuscript, Lynne Raymond for assistance in breeding the transgenic
mice, Katie Phillips for assistance with the stereotactic surgeries,
Jeffrey Severson for animal husbandry, Anita Mora for assistance with
digital figures, and Drs Gerald Baron and David Dorward for assistance
with confocal microscopy. This research was supported by the Division of
Intramural Research of the National Institute of Allergy and Infectious
Diseases, National Institutes of Health.
NR 31
TC 4
Z9 4
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0305-1846
J9 NEUROPATH APPL NEURO
JI Neuropathol. Appl. Neurobiol.
PD APR
PY 2013
VL 39
IS 3
BP 217
EP 230
DI 10.1111/j.1365-2990.2012.01303.x
PG 14
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 107BD
UT WOS:000316188800002
PM 22998478
ER
PT J
AU Sambataro, F
Mattay, VS
Thurin, K
Safrin, M
Rasetti, R
Blasi, G
Callicott, JH
Weinberger, DR
AF Sambataro, Fabio
Mattay, Venkata S.
Thurin, Kristina
Safrin, Martin
Rasetti, Roberta
Blasi, Giuseppe
Callicott, Joseph H.
Weinberger, Daniel R.
TI Altered Cerebral Response During Cognitive Control: A Potential
Indicator of Genetic Liability for Schizophrenia
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE response inhibition; functional magnetic resonance imaging; anterior
cingulate; heritability; intermediate phenotype
ID ANTERIOR CINGULATE CORTEX; WORKING-MEMORY; EFFECTIVE CONNECTIVITY; ONSET
SCHIZOPHRENIA; PREFRONTAL CORTEX; NETWORK DYNAMICS; DYSFUNCTION;
RELATIVES; INHIBITION; RISK
AB Aberrant activity in brain regions underlying various aspects of executive cognition has been reported in patients with schizophrenia and in their healthy relatives, suggesting an association with genetic liability. The aim of this study was to investigate brain responses to selective aspects of cognitive control in unaffected siblings who are at increased genetic risk of schizophrenia. Altogether, 65 non-affected siblings, 70 patients with schizophrenia spectrum disorders, and 235 normal controls participated in this study. Blood-oxygen-level-dependent functional magnetic resonance imaging was conducted while participants performed a cognitive control task ('flanker task') to identify brain activity and connectivity associated with response inhibition and conflict monitoring, and suppression. Behaviorally, similar to patients with schizophrenia, siblings were less accurate when inhibiting prepotent responses relative to normal controls. During response inhibition, again similar to patients with schizophrenia, siblings showed decreased activity in the anterior cingulate (ACC), along with increased functional coupling with the dorsolateral prefrontal cortex (PFC) when compared to normal controls. Our findings show altered ACC activity and PFC connectivity in unaffected siblings and patients with schizophrenia during response inhibition. These results suggest that such changes in the neural activity underlying aspects of cognitive control may represent a potential intermediate phenotype for the investigation of the genetic basis of schizophrenia. Neuropsychopharmacology (2013) 38, 846-853; doi:10.1038/npp.2012.250; published online 9 January 2013
C1 [Sambataro, Fabio] Ist Italiano Tecnol UNIPr, Brain Ctr Motor & Social Cognit, Parma, Italy.
[Sambataro, Fabio; Mattay, Venkata S.; Thurin, Kristina; Safrin, Martin; Rasetti, Roberta; Blasi, Giuseppe; Callicott, Joseph H.; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Mattay, Venkata S.; Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
RP Weinberger, DR (reprint author), Lieber Inst Brain Dev, Johns Hopkins Med Campus,855 North Wolfe St, Baltimore, MD 21205 USA.
EM drweinberger@libd.org
RI Sambataro, Fabio/E-3426-2010; Callicott, Joseph/C-9102-2009
OI Sambataro, Fabio/0000-0003-2102-416X; Callicott,
Joseph/0000-0003-1298-3334
FU National Institute of Mental Health, NIH, Bethesda, MD, USA
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health, NIH, Bethesda, MD 20892, USA.
NR 44
TC 14
Z9 14
U1 3
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD APR
PY 2013
VL 38
IS 5
BP 846
EP 853
DI 10.1038/npp.2012.250
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 106RB
UT WOS:000316161300013
PM 23299932
ER
PT J
AU Farrell, MS
Pei, Y
Wan, YH
Yadav, PN
Daigle, TL
Urban, DJ
Lee, HM
Sciaky, N
Simmons, A
Nonneman, RJ
Huang, XP
Hufeisen, SJ
Guettier, JM
Moy, SS
Wess, J
Caron, MG
Calakos, N
Roth, BL
AF Farrell, Martilias S.
Pei, Ying
Wan, Yehong
Yadav, Prem N.
Daigle, Tanya L.
Urban, Daniel J.
Lee, Hyeong-Min
Sciaky, Noah
Simmons, Arkeen
Nonneman, Randal J.
Huang, Xi-Ping
Hufeisen, Sandy J.
Guettier, Jean-Marc
Moy, Sheryl S.
Wess, Juergen
Caron, Marc G.
Calakos, Nicole
Roth, Bryan L.
TI A G alpha(s) DREADD Mouse for Selective Modulation of cAMP Production in
Striatopallidal Neurons
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE DREADD; striatopallidal; amphetamine; G-alpha-s; striatum; Gs
ID PROTEIN-COUPLED RECEPTORS; BEHAVIORAL SENSITIZATION; SYNAPTIC
PLASTICITY; DOPAMINE-RECEPTORS; NUCLEUS-ACCUMBENS; ADENOSINE A(2A);
GENE-EXPRESSION; REMOTE-CONTROL; DISORDERS; COCAINE
AB Here, we describe a newly generated transgenic mouse in which the Gs DREADD (rM3Ds), an engineered G protein-coupled receptor, is selectively expressed in striatopallidal medium spiny neurons (MSNs). We first show that in vitro, rM3Ds can couple to G alpha(olf) and induce cAMP accumulation in cultured neurons and HEK-T cells. The rM3Ds was then selectively and stably expressed in striatopallidal neurons by creating a transgenic mouse in which an adenosine2A (adora2a) receptor-containing bacterial artificial chromosome was employed to drive rM3Ds expression. In the adora2A-rM3Ds mouse, activation of rM3Ds by clozapine-N-oxide (CNO) induces DARPP-32 phosphorylation, consistent with the known consequence of activation of endogenous striatal G alpha(s)-coupled GPCRs. We then tested whether CNO administration would produce behavioral responses associated with striatopallidal G(s) signaling and in this regard CNO dose-dependently decreases spontaneous locomotor activity and inhibits novelty induced locomotor activity. Last, we show that CNO prevented behavioral sensitization to amphetamine and increased AMPAR/NMDAR ratios in transgene-expressing neurons of the nucleus accumbens shell. These studies demonstrate the utility of adora2a-rM3Ds transgenic mice for the selective and noninvasive modulation of G alpha(s) signaling in specific neuronal populations in vivo. This unique tool provides a new resource for elucidating the roles of striatopallidal MSN G alpha(s) signaling in other neurobehavioral contexts. Neuropsychopharmacology (2013) 38, 859-862; doi:10.1038/npp.2012.251; published online 16 January 2013
C1 [Farrell, Martilias S.; Pei, Ying; Yadav, Prem N.; Urban, Daniel J.; Lee, Hyeong-Min; Sciaky, Noah; Huang, Xi-Ping; Hufeisen, Sandy J.; Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Wan, Yehong; Caron, Marc G.; Calakos, Nicole] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Daigle, Tanya L.; Caron, Marc G.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
[Simmons, Arkeen] Elizabeth City State Univ, Elizabeth City, NC USA.
[Nonneman, Randal J.; Moy, Sheryl S.; Roth, Bryan L.] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA.
[Guettier, Jean-Marc; Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA.
[Moy, Sheryl S.; Roth, Bryan L.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA.
[Caron, Marc G.; Calakos, Nicole] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
[Roth, Bryan L.] Univ N Carolina, Program Neurosci, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, NIMH Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA.
RP Roth, BL (reprint author), Univ N Carolina, Chapel Hill Med Sch, Dept Pharmacol, Genet Med Bldg Room 4072, Chapel Hill, NC 27599 USA.
EM bryan_roth@med.unc.edu
RI Lee, HM/D-2777-2011; Roth, Bryan/F-3928-2010
FU NIH [1F31MH091921, RO1MH61887, U19MH82441]; NIMH Psychoactive Drug
Screening Program; Michael Hooker Chair in Pharmacology; NICHD [P30
HD03110, 5R37-MH-073853, 1F32-DA030026]; NIH; Forest Laboratories;
NeuroSearch; F Hoffmann La Roche; Lundbeck USA; Merck; Omeros;
[R01NS064577]; [K02NS054840]
FX This work was funded by NIH Grant # 1F31MH091921 to MSF and RO1MH61887,
U19MH82441, the NIMH Psychoactive Drug Screening Program and the Michael
Hooker Chair in Pharmacology to BLR, R01NS064577 and K02NS054840 to NC,
NICHD Grant #P30 HD03110 to Joe Piven (UNC), 5R37-MH-073853 to MCG, and
1F32-DA030026 to TLD.; Dr Roth's research is supported by the NIH. Dr
Roth has consulted for Otsuka Pharmaceuticals, Merck, Sunovion, Albany
Molecular Research, Pfizer Pharmaceuticals, Finnegan, Henderson,
Farabow, Garrett And Dunner, L.l.p, and Venrock. Dr Roth receives
compensation for serving as Associate Editor of the Journal of Clinical
Investigation. MGC has received funds for Sponsored Research Agreements
unrelated to this work from Forest Laboratories, NeuroSearch, F Hoffmann
La Roche and Lundbeck USA, as well as consulting fees from Merck and
Omeros. An unrestricted gift to Duke University was provided by Lundbeck
USA to support Neuroscience research unrelated to this work in the
laboratory of MGC MSF, YP, YW, PNY, TLD, NS, AS, RJN, XH, SJH, JMG, SSM,
JW, and NC report no conflict of interest and have nothing to disclose.
NR 39
TC 34
Z9 35
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD APR
PY 2013
VL 38
IS 5
BP 854
EP 862
DI 10.1038/npp.2012.251
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 106RB
UT WOS:000316161300014
PM 23303063
ER
PT J
AU Turtzo, LC
Budde, MD
Gold, EM
Lewis, BK
Janes, L
Yarnell, A
Grunberg, NE
Watson, W
Frank, JA
AF Turtzo, L. Christine
Budde, Matthew D.
Gold, Eric M.
Lewis, Bobbi K.
Janes, Lindsay
Yarnell, Angela
Grunberg, Neil E.
Watson, William
Frank, Joseph A.
TI The evolution of traumatic brain injury in a rat focal contusion model
SO NMR IN BIOMEDICINE
LA English
DT Article
DE traumatic brain injury; controlled cortical impact; MRI; hemorrhage;
autofluorescence
ID CONTROLLED CORTICAL IMPACT; GADOLINIUM OXIDE NANOPARTICLES;
CENTRAL-NERVOUS-SYSTEM; MARROW STROMAL CELLS; NEURAL STEM-CELLS;
SUPERFICIAL SIDEROSIS; HEAD-INJURY; VASCULAR DISRUPTION; FEMALE RATS;
IN-VIVO
AB Serial MRI facilitates the in vivo analysis of the intra- and intersubject evolution of traumatic brain injury lesions. Despite the availability of MRI, the natural history of experimental focal contusion lesions in the controlled cortical impact (CCI) rat model has not been well described. We performed CCI on rats and MRI during the acute to chronic stages of cerebral injury to investigate the time course of changes in the brain. Female Wistar rats underwent CCI of their left motor cortex with a flat impact tip driven by an electromagnetic piston. In vivo MRI was performed at 7T serially over 6weeks post-CCI. The appearances of CCI-induced lesions and lesion-associated cortical volumes were variable on MRI, with the percentage change in cortical volume of the CCI ipsilateral side relative to the contralateral side ranging from 18% within 2h of injury on day 0 to a peak of 35% on day 1, and a trough of 28% by week 5/6, with an average standard deviation of +/- 14% at any given time point. In contrast, the percentage change in cortical volume of the ipsilateral side relative to the contralateral side in control rats was not significant (1 +/- 2%). Hemorrhagic conversion within and surrounding the CCI lesion occurred between days 2 and 9 in 45% of rats, with no hemorrhage noted on the initial scan. Furthermore, hemorrhage and hemosiderin within the lesion were positive for Prussian blue and highly autofluorescent on histological examination. Although some variation in injuries may be technique related, the divergence of similar lesions between initial and final scans demonstrates the inherent biological variability of the CCI rat model. Published 2012. This article is a US Government work and is in the public domain in the USA.
C1 [Turtzo, L. Christine; Gold, Eric M.; Janes, Lindsay] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Turtzo, L. Christine; Budde, Matthew D.; Gold, Eric M.; Lewis, Bobbi K.; Janes, Lindsay; Frank, Joseph A.] NIH, Frank Lab, Bethesda, MD 20892 USA.
[Yarnell, Angela; Grunberg, Neil E.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Watson, William] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA.
[Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
RP Turtzo, LC (reprint author), NIH, Frank Lab, Bldg 10,Room B1N256 MSC 1074,10 Ctr Dr, Bethesda, MD 20892 USA.
EM l.turtzo@nih.gov; jafrank@helix.nih.gov
FU Department of Defense through the Center for Neuroscience and
Regenerative Medicine [300604-8.01-60855]; Intramural Research Program
of the Clinical Center at the National Institutes of Health
FX This work was supported by funding from the Department of Defense
through the Center for Neuroscience and Regenerative Medicine (Henry M.
Jackson Foundation Award #300604-8.01-60855) and from the Intramural
Research Program of the Clinical Center at the National Institutes of
Health.
NR 78
TC 7
Z9 7
U1 1
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD APR
PY 2013
VL 26
IS 4
BP 468
EP 479
DI 10.1002/nbm.2886
PG 12
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 107IK
UT WOS:000316209200014
PM 23225324
ER
PT J
AU Seidel, J
Xi, WZ
Kakareka, JW
Pohida, TJ
Jagoda, EM
Green, MV
Choyke, PL
AF Seidel, Jurgen
Xi, Wenze
Kakareka, John W.
Pohida, Thomas J.
Jagoda, Elaine M.
Green, Michael V.
Choyke, Peter L.
TI Performance characteristics of a positron projection imager for mouse
whole-body imaging
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
DE Pre-clinical imaging; Cancer drug development; Mouse whole-body imaging;
Positron projection imaging
ID EMISSION MAMMOGRAPHY PEM; SYSTEM
AB Introduction: We describe a prototype positron projection imager (PPI) for visualizing the whole-body biodistribution of positron-emitting compounds in mouse-size animals. The final version of the PPI will be integrated into the MONICA portable dual-gamma camera system to allow the user to interchangeably image either single photon or positron-emitting compounds in a shared software and hardware environment.
Methods: A Mouse is placed in the mid-plane between two identical, opposed, pixelated LYSO arrays separated by 21.8-cm and in time coincidence. An image of the distribution of positron decays in the animal is formed on this mid-plane by coincidence events that fall within a small cone angle perpendicular to the two detectors and within a user-specified energy window. We measured the imaging performance of this device with phantoms and in tests performed in mice injected with various compounds labeled with positron-emitting isotopes.
Results: Representative performance measurements yielded the following results (energy window 250-d650 keV, cone angle 3.5 degrees): resolution in the image mid-plane, 1.66-mm (FWHM), resolution +/- 1.5-cm above and below the image plane, 2.2-mm (FWHM), sensitivity: 0.237-cps/kBq (8.76-cps/mu Ci) F-18 (0.024% absolute). Energy resolution was 15.9% with a linear-count-rate operating range of 0-14.8 MBq (0-400 mu Ci) and a corrected sensitivity variation across the field-of-view of <3%. Whole-body distributions of [F-18] FDG and [F-18] fluoride were well visualized in mice of typical size.
Conclusion: Performance measurements and field studies indicate that the PPI is well suited to whole-body positron projection imaging of mice. When integrated into the MONICA gamma camera system, the PPI may be particularly useful early in the drug development cycle where, like MONICA, basic whole-body biodistribution data can direct future development of the agent under study and where logistical factors (e.g., available imaging space, non-portability, and cost) may be limitations. Published by Elsevier Inc.
C1 [Seidel, Jurgen; Xi, Wenze; Jagoda, Elaine M.; Green, Michael V.; Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Seidel, Jurgen; Xi, Wenze; Green, Michael V.] SAIC Frederick, Frederick, MD USA.
[Kakareka, John W.; Pohida, Thomas J.] NIH, Signal Proc & Instrumentat Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Choyke, PL (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room B3B69,MSC1088, Bethesda, MD 20892 USA.
EM pchoyke@mail.nih.gov
OI Kakareka, John/0000-0003-0072-0035
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Intramural Research Program, National Institutes of
Health, Center for Information Technology
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 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 also supported by the Intramural Research Program,
National Institutes of Health, Center for Information Technology.
NR 11
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 0969-8051
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD APR
PY 2013
VL 40
IS 3
BP 321
EP 330
DI 10.1016/j.nucmedbio.2012.12.003
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 111FP
UT WOS:000316507400003
PM 23402672
ER
PT J
AU Koo, E
Chang, JR
Agron, E
Clemons, TE
Sperduto, RD
Ferris, FL
Chew, EY
AF Koo, Euna
Chang, Jessica R.
Agron, Elvira
Clemons, Traci E.
Sperduto, Robert D.
Ferris, Frederick L., III
Chew, Emily Y.
CA Age-Related Eye Dis Study Res Grp
TI Ten-Year Incidence Rates of Age-Related Cataract in the Age-Related Eye
Disease Study (AREDS): AREDS Report No. 33
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE cataract; classification; incidence; lens; photographic
ID BEAVER DAM EYE; VISUAL IMPAIRMENT; LENS OPACITIES; UNITED-STATES;
POPULATION; PREVALENCE; INTERVAL; SURGERY; ADULTS; CARE
AB Purpose: To investigate the long-term incidence of age-related cataract and cataract surgery in the Age-Related Eye Disease Study (AREDS) cohort.
Methods: Baseline and annual lens photographs of participants, aged 55-80 years, were graded centrally for nuclear, cortical, and posterior subcapsular (PSC) lens opacities using the AREDS System for Classifying Cataracts. Progression from a baseline status of no or mild lens opacity to at least moderate severity was analyzed and cumulative incidence estimated rates were calculated for each lens opacity type and cataract surgery stratified by age, sex, race, age-related macular degeneration category, multivitamin (Centrum) use and history of diabetes.
Results: The ten-year cumulative incidence was 43.6% for any cataract, 23.1% for nuclear cataract, 22.0% for cortical cataract, 13.1% for PSC cataract, and 26.8% for cataract surgery. The 5-and 10-year incidence rates of all cataract types and cataract surgery were significantly higher with increasing age. Females had a higher incidence of any, nuclear and cortical cataract and cataract surgery (p=0.02-0.05). Incidence of cortical cataract was higher in non-white participants (p=0.001).
Conclusions: These results are largely consistent with the results of previous observational studies. Long-term incidence rates of type-specific cataract can be useful in designing clinical studies of age-related cataract.
C1 [Koo, Euna; Agron, Elvira; Ferris, Frederick L., III; Chew, Emily Y.] NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Chang, Jessica R.] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Clemons, Traci E.; Sperduto, Robert D.] EMMES Corp, Rockville, MD USA.
RP Chew, EY (reprint author), NEI, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
FU National Eye Institute/National Institutes of Health, Department of
Health and Human Services, Bethesda, MD; NIH; Pfizer; Howard Hughes
Medical Institute-National Institutes of Health Scholars Program
FX This study is supported by the intramural program funds and contracts
from the National Eye Institute/National Institutes of Health,
Department of Health and Human Services, Bethesda, MD. The first two
authors receive support from a public-private partnership supported
jointly by the NIH and Pfizer for the Clinical Research Training Program
at the National Institutes of Health (Euna Koo) and the Howard Hughes
Medical Institute-National Institutes of Health Scholars Program
(Jessica R. Chang).
NR 20
TC 6
Z9 6
U1 0
U2 16
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0928-6586
J9 OPHTHAL EPIDEMIOL
JI Ophthalmic Epidemiol.
PD APR
PY 2013
VL 20
IS 2
BP 71
EP 81
DI 10.3109/09286586.2012.759598
PG 11
WC Ophthalmology
SC Ophthalmology
GA 110BZ
UT WOS:000316418400001
PM 23510310
ER
PT J
AU Clemons, TE
Gillies, MC
Chew, EY
Bird, AC
Peto, T
Wang, JJ
Mitchell, P
Ramdas, WD
Vingerling, JR
AF Clemons, Traci E.
Gillies, Mark C.
Chew, Emily Y.
Bird, Alan C.
Peto, Tunde
Wang, Jie Jin
Mitchell, Paul
Ramdas, Wishal D.
Vingerling, Johannes R.
CA Macular Telangiectasia Project Res
TI Medical Characteristics of Patients with Macular Telangiectasia Type 2
(MacTel Type 2) MacTel Project Report No. 3
SO OPHTHALMIC EPIDEMIOLOGY
LA English
DT Article
DE Cohort Study; diabetes; idiopathic macular telangiectasia; macular
telangiectasia type 2; retinal disease
ID JUXTAFOVEOLAR RETINAL TELANGIECTASIS; DIABETIC-RETINOPATHY; PREVALENCE;
EYE
AB Purpose: To determine whether the prevalences of various systemic conditions in participants of the MacTel Project Natural History Observation (NHO) Study differ from the corresponding prevalences in the general population.
Methods: This report compares the prevalence of systemic disease in participants of the NHO Study with age- and sex-matched controls from three population-based studies from the US, the Netherlands and Australia. Bootstrap simulations were used to evaluate the impact and reliability of the computed statistics.
Results: We identified a number of systemic conditions that appear to be more prevalent in cases with macular telangiectasia (MacTel) Type 2 than in the general population that were matched for age and sex with the MacTel cases. Patients with MacTel Type 2 had significantly increased prevalence of diabetes mellitus, higher prevalence of obesity, hypertension and history of cardiovascular disease, compared to their same-aged peers in generally older communities.
Conclusion: Systemic disease associated with MacTel Type 2 may help to improve understanding of possible causes of MacTel Type 2. It is hoped that future studies will help to improve our understanding of the pathogenesis of the condition and lead to potential treatments for this ocular disease.
C1 [Clemons, Traci E.] EMMES Corp, Rockville, MD 20850 USA.
[Gillies, Mark C.] Univ Sydney, Save Sight Inst, Sydney, NSW 2006, Australia.
[Chew, Emily Y.] NEI, Bethesda, MD 20892 USA.
[Bird, Alan C.; Peto, Tunde] Moorfields Eye Hosp, London, England.
[Wang, Jie Jin; Mitchell, Paul] Univ Sydney, Westmead Millennium Inst, Ctr Vis Res, Sydney, NSW 2006, Australia.
[Ramdas, Wishal D.; Vingerling, Johannes R.] Erasmus Univ, Dept Ophthalmol & Epidemiol, Rotterdam, Netherlands.
RP Clemons, TE (reprint author), EMMES Corp, 401 N Washington St Suite 700, Rockville, MD 20850 USA.
EM tclemons@emmes.com
RI Wang, Jie Jin/P-1499-2014; Mitchell, Paul/P-1498-2014
OI Wang, Jie Jin/0000-0001-9491-4898;
NR 17
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 0928-6586
J9 OPHTHAL EPIDEMIOL
JI Ophthalmic Epidemiol.
PD APR
PY 2013
VL 20
IS 2
BP 109
EP 113
DI 10.3109/09286586.2013.766757
PG 5
WC Ophthalmology
SC Ophthalmology
GA 110BZ
UT WOS:000316418400006
PM 23510315
ER
PT J
AU Panlilio, LV
Justinova, Z
Goldberg, SR
AF Panlilio, Leigh V.
Justinova, Zuzana
Goldberg, Steven R.
TI Inhibition of FAAH and activation of PPAR: New approaches to the
treatment of cognitive dysfunction and drug addiction
SO PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
DE Endocannabinoid system; CB1 receptors; Nuclear receptors; Behavior; Drug
abuse; Animal models
ID ACID-AMIDE-HYDROLASE; CONDITIONED PLACE PREFERENCE; CANNABINOID CB1
RECEPTOR; CHRONIC DELTA-9-TETRAHYDROCANNABINOL TREATMENT;
BRAIN-STIMULATION REWARD; VENTRAL TEGMENTAL AREA; INDUCED BEHAVIORAL
SENSITIZATION; INTRACRANIAL SELF-STIMULATION; VOLUNTARY
ALCOHOL-CONSUMPTION; NUCLEUS-ACCUMBENS DOPAMINE
AB Enhancing the effects of endogenously-released cannabinoid ligands in the brain might provide therapeutic effects more safely and effectively than administering drugs that act directly at the cannabinoid receptor. Inhibitors of fatty acid amide hydrolase (FAAH) prevent the breakdown of endogenous ligands for cannabinoid receptors and peroxisome proliferator-activated receptors (PPAR), prolonging and enhancing the effects of these ligands when they are naturally released. This review considers recent research on the effects of FAAH inhibitors and PPAR activators in animal models of addiction and cognition (specifically learning and memory). These studies show that FAAH inhibitors can produce potentially therapeutic effects, some through cannabinoid receptors and some through PPAR. These effects include enhancing certain forms of learning, counteracting the rewarding effects of nicotine and alcohol, relieving symptoms of withdrawal from cannabis and other drugs, and protecting against relapse-like reinstatement of drug self-administration. Since FAAH inhibition might have a wide range of therapeutic actions but might also share some of the adverse effects of cannabis, it is noteworthy that at least one FAAH-inhibiting drug (URB597) has been found to have potentially beneficial effects but no indication of liability for abuse or dependence. Although these areas of research are new, the preliminary evidence indicates that they might lead to improved therapeutic interventions and a better understanding of the brain mechanisms underlying addiction and memory. Published by Elsevier Inc.
C1 [Panlilio, Leigh V.; Justinova, Zuzana; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Justinova, Zuzana] Univ Maryland, Dept Psychiat, Maryland Psychiat Res Ctr, Sch Med, Baltimore, MD 21228 USA.
RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Sect, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sgoldber@mail.nih.gov
RI Justinova, Zuzana/A-9109-2011
OI Justinova, Zuzana/0000-0001-5793-7484
FU Intramural Research Program of the National Institute on Drug Abuse,
National Institutes of Health, Department of Health and Human Services;
Department of Psychiatry, MPRC, University of Maryland School of
Medicine
FX Preparation of this manuscript was supported by the Intramural Research
Program of the National Institute on Drug Abuse, National Institutes of
Health, Department of Health and Human Services and Department of
Psychiatry, MPRC, University of Maryland School of Medicine.
NR 331
TC 37
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U1 3
U2 31
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0163-7258
J9 PHARMACOL THERAPEUT
JI Pharmacol. Ther.
PD APR
PY 2013
VL 138
IS 1
BP 84
EP 102
DI 10.1016/j.pharmthera.2013.01.003
PG 19
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 111KQ
UT WOS:000316520600007
PM 23333350
ER
PT J
AU Chen, MY
Shanbhag, SM
Arai, AE
AF Chen, Marcus Y.
Shanbhag, Sujata M.
Arai, Andrew E.
TI Submillisievert Median Radiation Dose for Coronary Angiography with a
Second-Generation 320-Detector Row CT Scanner in 107 Consecutive
Patients
SO RADIOLOGY
LA English
DT Article
ID COMPUTED TOMOGRAPHIC ANGIOGRAPHY; ACUTE CHEST-PAIN; IMAGE-QUALITY;
DIAGNOSTIC-ACCURACY; ITERATIVE RECONSTRUCTION; ARTERY-DISEASE;
HEART-RATE; EXPOSURE; PERFORMANCE; MULTICENTER
AB Purpose: To (a) use a new second-generation wide-volume 320-detector row computed tomographic (CT) scanner to explore optimization of radiation exposure in coronary CT angiography in an unselected and consecutive cohort of patients referred for clinical purposes and (b) compare estimated radiation exposure and image quality with that from a cohort of similar patients who underwent imaging with a previous first-generation CT system.
Materials and Methods: The study was approved by the institutional review board, and all subjects provided written consent. Coronary CT angiography was performed in 107 consecutive patients with a new second-generation 320-detector row unit. Estimated radiation exposure and image quality were compared with those from 100 consecutive patients who underwent imaging with a previous first-generation scanner. Effective radiation dose was estimated by multiplying the dose-length product by an effective dose conversion factor of 0.014 mSv/mGy . cm and reported with size-specific dose estimates (SSDEs). Image quality was evaluated by two independent readers.
Results: The mean age of the 107 patients was 55.4 years +/- 12.0 (standard deviation); 57 patients (53.3%) were men. The median body mass index was 27.3 kg/m(2) (range, 18.1-47.2 kg/m(2)); however, 71 patients (66.4%) were overweight, obese, or morbidly obese. A tube potential of 100 kV was used in 97 patients (90.6%), single-volume acquisition was used in 104 (97.2%), and prospective electrocardiographic gating was used in 106 (99.1%). The mean heart rate was 57.1 beats per minute +/- 11.2 (range, 34-96 beats per minute), which enabled single-heartbeat scans in 100 patients (93.4%). The median radiation dose was 0.93 mSv (interquartile range [IQR], 0.58-1.74 mSv) with the second-generation unit and 2.67 mSv (IQR, 1.68-4.00 mSv) with the first-generation unit (P < .0001). The median SSDE was 6.0 mGy (IQR, 4.1-10.0 mGy) with the second-generation unit and 13.2 mGy (IQR, 10.2-18.6 mGy) with the first-generation unit (P < .0001). Overall, the radiation dose was less than 0.5 mSv for 23 of the 107 CT angiography examinations (21.5%), less than 1 mSv for 58 (54.2%), and less than 4 mSv for 103 (96.3%). All studies were of diagnostic quality, with most having excellent image quality. Three of four image quality indexes were significantly better with the second-generation unit compared with the first-generation unit.
Conclusion: The combination of a gantry rotation time of 275 msec, wide volume coverage, iterative reconstruction, automated exposure control, and larger x-ray power generator of the second-generation CT scanner provides excellent image quality over a wide range of body sizes and heart rates at low radiation doses. (c) RSNA, 2013
C1 [Chen, Marcus Y.; Shanbhag, Sujata M.; Arai, Andrew E.] NHLBI, Adv Cardiovasc Imaging Lab, Cardiovasc & Pulm Branch, NIH,US Dept HHS, Bethesda, MD 20892 USA.
RP Chen, MY (reprint author), NHLBI, Adv Cardiovasc Imaging Lab, Cardiovasc & Pulm Branch, NIH,US Dept HHS, 10 Ctr Dr,Bldg 10,Room B1D416, Bethesda, MD 20892 USA.
EM marcus.chen@nih.gov
FU National Institutes of Health [HL006138-02]
FX This research was supported by the National Institutes of Health (grant
HL006138-02).
NR 39
TC 60
Z9 63
U1 1
U2 8
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD APR
PY 2013
VL 267
IS 1
BP 76
EP 85
DI 10.1148/radiol.13122621
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 112AX
UT WOS:000316565000008
PM 23340461
ER
PT J
AU Nayak, TK
Bernardo, M
Milenic, DE
Choyke, PL
Brechbiel, MW
AF Nayak, Tapan K.
Bernardo, Marcelino
Milenic, Diane E.
Choyke, Peter L.
Brechbiel, Martin W.
TI Orthotopic Pleural Mesothelioma in Mice: SPECT/CT and MR Imaging with
HER1- and HER2-targeted Radiolabeled Antibodies
SO RADIOLOGY
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; MALIGNANT MESOTHELIOMA; PHASE-II; EXPRESSION;
STIMULATION; CANCER
AB Purpose: To evaluate the potential of anti-human epidermal growth factor receptor (HER) 1- and anti-HER2-targeted radio-labeled antibodies and magnetic resonance (MR) imaging for imaging of orthotopic malignant pleural mesothelioma (MPM) in mouse models.
Materials and Methods: Animal studies with 165 mice were performed in accordance with National Institutes of Health guidelines for the humane use of animals, and all procedures were approved by the institutional Animal Care and Use Committee. Flow cytometry studies were performed to evaluate HER1 and HER2 expression in NCI-H226 and MSTO-211H mesothelioma cells. Biodistribution and single photon emission computed tomography (SPECT)/computed tomography (CT) imaging studies were performed in mice (four or five per group, depending on tumor growth) bearing subcutaneous and orthotopic MPM tumors by using HER1- and HER2-targeted indium 111 (In-111)- and iodine 125 (I-125)-labeled panitumumab and trastuzumab, respectively. Longitudinal MR imaging over 5 weeks was performed in three mice bearing orthotopic tumors to monitor tumor growth and metastases. SPECT/CT/MR imaging studies were performed at the final time point in the orthotopic models (n = 3). The standard unpaired Student t test was used to compare groups.
Results: Orthotopic tumors and pleural effusions were clearly visualized at MR imaging 3 weeks after tumor cell inoculation. At 2 days after injection, the mean In-111-panitumumab uptake of 29.6% injected dose (ID) per gram +/- 2.2 (standard error of the mean) was significantly greater than the In-111-trastuzumab uptake of 13.6% ID/g +/- 1.0 and the I-125-panitumumab uptake of 7.4% ID/g +/- 1.2 (P = .0006 and P = .0001, respectively). MR imaging fusion with SPECT/CT provided more accurate information about In-111-panitumumab localization in the tumor, as the tumor was poorly visualized at CT alone.
Conclusion: This study demonstrates the utility of radiolabeled anti-HER1 antibodies in the imaging of MPM in preclinical models. (C)RSNA, 2013
C1 [Nayak, Tapan K.; Milenic, Diane E.; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Bernardo, Marcelino; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Bernardo, Marcelino] NCI, SAIC Frederick, Dept Imaging Phys, Frederick, MD 21701 USA.
RP Nayak, TK (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, 10 Ctr Dr,MSC 1182,Bldg 10,Room B3B69F, Bethesda, MD 20892 USA.
EM tapann@gmail.com
OI Nayak, Tapan/0000-0002-3706-6092
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research; U.S. Department
of Health and Human Services
FX All authors are employees of the National Cancer Institute, National
Institutes of Health. This research was supported by the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Center for Cancer Research, and the U.S. Department of Health
and Human Services.
NR 22
TC 5
Z9 5
U1 0
U2 7
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD APR
PY 2013
VL 267
IS 1
BP 173
EP 182
DI 10.1148/radiol.12121021
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 112AX
UT WOS:000316565000018
PM 23329660
ER
PT J
AU Kudo, K
Christensen, S
Sasaki, M
Ostergaard, L
Shirato, H
Ogasawara, K
Wintermark, M
Warach, S
AF Kudo, Kohsuke
Christensen, Soren
Sasaki, Makoto
Ostergaard, Leif
Shirato, Hiroki
Ogasawara, Kuniaki
Wintermark, Max
Warach, Steven
CA Stroke Imaging Repository STIR Inv
TI Accuracy and Reliability Assessment of CT and MR Perfusion Analysis
Software Using a Digital Phantom
SO RADIOLOGY
LA English
DT Article
ID FINAL INFARCT VOLUME; ACUTE STROKE; DYNAMIC CT; PREDICTION; FLOW;
OCCLUSION; BRAIN; DELAY; MODEL; MAPS
AB Purpose: To design a digital phantom data set for computed tomography (CT) perfusion and perfusion-weighted imaging on the basis of the widely accepted tracer kinetic theory in which the true values of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and tracer arrival delay are known and to evaluate the accuracy and reliability of postprocessing programs using this digital phantom.
Materials and Methods: A phantom data set was created by generating concentration-time curves reflecting true values for CBF (2.5-87.5 mL/100 g per minute), CBV (1.0-5.0 mL/100 g), MTT (3.4-24 seconds), and tracer delays (0-3.0 seconds). These curves were embedded in human brain images. The data were analyzed by using 13 algorithms each for CT and magnetic resonance (MR), including five commercial vendors and five academic programs. Accuracy was assessed by using the Pearson correlation coefficient (r) for true values. Delay-, MTT-, or CBV-dependent errors and correlations between time to maximum of residue function (T-max) were also evaluated.
Results: In CT, CBV was generally well reproduced (r > 0.9 in 12 algorithms), but not CBF and MTT (r > 0.9 in seven and four algorithms, respectively). In MR, good correlation (r > 0.9) was observed in one-half of commercial programs, while all academic algorithms showed good correlations for all parameters. Most algorithms had delay-dependent errors, especially for commercial software, as well as CBV dependency for CBF or MTT calculation and MTT dependency for CBV calculation. Correlation was good in T-max except for one algorithm.
Conclusion: The digital phantom readily evaluated the accuracy and characteristics of the CT and MR perfusion analysis software. All commercial programs had delay-induced errors and/or insufficient correlations with true values, while academic programs for MR showed good correlations with true values. (C) RSNA, 2012
C1 [Kudo, Kohsuke; Sasaki, Makoto] Iwate Med Univ, Div Ultra High Field MRI, Morioka, Iwate 0208505, Japan.
[Kudo, Kohsuke; Sasaki, Makoto] Iwate Med Univ, Dept Radiol, Morioka, Iwate 0208505, Japan.
[Ogasawara, Kuniaki] Iwate Med Univ, Dept Neurosurg, Morioka, Iwate 0208505, Japan.
[Christensen, Soren] Univ Melbourne, Royal Melbourne Hosp, Dept Neurol, Melbourne, Vic 3050, Australia.
[Christensen, Soren] Univ Melbourne, Royal Melbourne Hosp, Dept Radiol, Melbourne, Vic 3050, Australia.
[Ostergaard, Leif] Arhus Univ Hosp, Dept Neuroradiol, Ctr Functionally Integrat Neurosci, Aarhus, Denmark.
[Shirato, Hiroki] Hokkaido Univ, Grad Sch Med, Dept Radiol, Sapporo, Hokkaido, Japan.
[Wintermark, Max] Univ Virginia, Dept Radiol, Charlottesville, VA USA.
[Warach, Steven] NINDS, NIH, Bethesda, MD 20892 USA.
RP Kudo, K (reprint author), Iwate Med Univ, Div Ultra High Field MRI, 19-1 Uchimaru, Morioka, Iwate 0208505, Japan.
EM kokudo@iwate-med.ac.jp
RI Shirato, Hiroki/A-7068-2010; Ostergaard, Leif/A-9281-2008;
OI Ostergaard, Leif/0000-0003-2930-6997; Wintermark,
Max/0000-0002-6726-3951
FU Ministry of Education, Culture, Sports, Science and Technology of Japan;
Japan Society for the Promotion of Science; Council for Science and
Technology Policy; Medical Image Lab; Lundbeck; Hitachi Medical;
Hitachi; Varian Medical Systems; Shimadzu; Hokkaido Electric Power;
Elekta K. K.; Accuthera; Tanaka Kikinzoku Kogyo K. K.; Medikit;
Mitsubishi Heavy Industries; Philips Electronics Japan; Fujifilm
Medical; Sumitomo Heavy Industries; Asahikawa Medical University;
Nakashima Medical; Hokkaido Gastrointestinal Cancer Study group; GE
Healthcare
FX Supported in part by a Grant-in-Aid for Strategic Medical Science
Research from the Ministry of Education, Culture, Sports, Science and
Technology of Japan and by the Japan Society for the Promotion of
Science through the Funding Program for Next Generation World-Leading
Researchers (NEXT Program) initiated by the Council for Science and
Technology Policy.; S.W. is an employee of the National Institute of
Neurological Disorders and Stroke, National Institutes of Health.; K. K.
Financial activities related to the present article: none to disclose.
Financial activities not related to the present article: was paid
consultancy fee by Medical Image Lab and received payment for lectures
including service on speakers bureaus by GE Healthcare and Hitachi
Medical Corporation. Other relationships: none to disclose. S. C. No
relevant conflicts of interest to disclose. M. S. Financial activities
related to the present article: none to disclose. Financial activities
not related to the present article: author was paid consultancy fee by
Lundbeck; institution was paid consultancy fee by Hitachi Medical; was
paid for lectures including service on speakers bureaus by GE
Healthcare, Otsuka Pharma, Mitsubishi Pharma, Daiichi Pharma, J-Mac
System, Hitachi Medical, Olea Medical, Bayer, Sanofi, and Esai. Other
relationships: none to disclose. L.O. No relevant conflicts of interest
to disclose. H. S. Financial activities related to the present article:
none to disclose. Financial activities not related to the present
article: paid for board membership by the Japanese Organization of
Radiotherapy Quality Management and for consultancy by Medical Image
Lab; institution received grants from Hitachi, Hitachi Medical, Varian
Medical Systems, Shimadzu, Hokkaido Electric Power, and Elekta K. K.;
institution received collaborative research grants from Accuthera,
Tanaka Kikinzoku Kogyo K. K., Medikit, Mitsubishi Heavy Industries,
Philips Electronics Japan, Fujifilm Medical, Sumitomo Heavy Industries,
Shimadzu, Asahikawa Medical University, Nakashima Medical, Hokkaido
Gastrointestinal Cancer Study group; institution received consigned
research grants from Fujifilm Medical; received payment for lectures
including service on speakers bureaus from Moroo, Hitachi, Chiyoda
Technol, Japan Society of Medical Physics, Olympus, Varian Medical
Systems, and ORIX Life Insurance. Other relationships: none to disclose.
K. O. No relevant conflicts of interest to disclose. M. W. Financial
activities related to the present article: none to disclose. Financial
activities not related to the present article: institution received a
grant from GE Healthcare. Other relationships: none to disclose. S. W.
No relevant conflicts of interest to disclose.
NR 22
TC 36
Z9 36
U1 0
U2 4
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD APR
PY 2013
VL 267
IS 1
BP 201
EP 211
DI 10.1148/radiol.12112618
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 112AX
UT WOS:000316565000021
PM 23220899
ER
PT J
AU Jain, R
Poisson, L
Narang, J
Gutman, D
Scarpace, L
Hwang, SN
Holder, C
Wintermark, M
Colen, RR
Kirby, J
Freymann, J
Brat, DJ
Jaffe, C
Mikkelsen, T
AF Jain, Rajan
Poisson, Laila
Narang, Jayant
Gutman, David
Scarpace, Lisa
Hwang, Scott N.
Holder, Chad
Wintermark, Max
Colen, Rivka R.
Kirby, Justin
Freymann, John
Brat, Daniel J.
Jaffe, Carl
Mikkelsen, Tom
TI Genomic Mapping and Survival Prediction in Glioblastoma: Molecular
Subclassification Strengthened by Hemodynamic Imaging Biomarkers
SO RADIOLOGY
LA English
DT Article
ID CEREBRAL BLOOD-VOLUME; GENE-EXPRESSION; MICROARRAY ANALYSIS; TUMOR
GRADE; GLIOMAS; MR; MULTIFORME; PROGRESSION; PROGNOSIS; SUBTYPES
AB Purpose: To correlate tumor blood volume, measured by using dynamic susceptibility contrast material-enhanced T2*-weighted magnetic resonance (MR) perfusion studies, with patient survival and determine its association with molecular subclasses of glioblastoma (GBM).
Materials and Methods: This HIPAA-compliant retrospective study was approved by institutional review board. Fifty patients underwent dynamic susceptibility contrast-enhanced T2*-weighted MR perfusion studies and had gene expression data available from the Cancer Genome Atlas. Relative cerebral blood volume (rCBV) (maximum rCBV [rCBV(max)] and mean rCBV [rCBV(mean)]) of the contrast-enhanced lesion as well as rCBV of the nonenhanced lesion (rCBV(NEL)) were measured. Patients were subclassified according to the Verhaak and Phillips classification schemas, which are based on similarity to defined genomic expression signature. We correlated rCBV measures with the molecular subclasses as well as with patient overall survival by using Cox regression analysis.
Results: No statistically significant differences were noted for rCBV(max), rCBV(mean) of contrast-enhanced lesion or rCBV(NEL) between the four Verhaak classes or the three Phillips classes. However, increased rCBV measures are associated with poor overall survival in GBM. The rCBV(max) (P = .0131) is the strongest predictor of overall survival regardless of potential confounders or molecular classification. Interestingly, including the Verhaak molecular GBM classification in the survival model clarifies the association of rCBV(mean) with patient overall survival (hazard ratio: 1.46, P = .0212) compared with rCBV(mean) alone (hazard ratio: 1.25, P = .1918). Phillips subclasses are not predictive of overall survival nor do they affect the predictive ability of rCBV measures on overall survival.
Conclusion: The rCBV(max) measurements could be used to predict patient overall survival independent of the molecular subclasses of GBM; however, Verhaak classifiers provided additional information, suggesting that molecular markers could be used in combination with hemodynamic imaging biomarkers in the future. (C)RSNA, 2012
C1 [Jain, Rajan; Narang, Jayant] Henry Ford Hlth Syst, Div Neuroradiol, Dept Radiol, Detroit, MI 48202 USA.
[Jain, Rajan; Scarpace, Lisa; Mikkelsen, Tom] Henry Ford Hlth Syst, Dept Neurosurg, Detroit, MI 48202 USA.
[Poisson, Laila] Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI 48202 USA.
[Gutman, David; Brat, Daniel J.] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA.
[Gutman, David; Brat, Daniel J.] Emory Univ, Sch Med, Dept Lab Med, Atlanta, GA USA.
[Hwang, Scott N.; Holder, Chad] Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA.
[Wintermark, Max] Univ Virginia, Dept Radiol, Charlottesville, VA USA.
[Colen, Rivka R.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Kirby, Justin; Freymann, John] NCI, Clin Res Directorate, CMRP, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Jaffe, Carl] Boston Univ, Dept Radiol, Boston, MA 02215 USA.
RP Jain, R (reprint author), Henry Ford Hlth Syst, Div Neuroradiol, Dept Radiol, 2799 W Grand Blvd, Detroit, MI 48202 USA.
EM rajanj@rad.hfh.edu
RI Narang, Jayant/L-6510-2013;
OI Hwang, Scott/0000-0002-6496-2087; Wintermark, Max/0000-0002-6726-3951
FU National Institutes of Health [HHSN261200800001E]; GE Healthcare;
Philips Healthcare; NIH; Merck Schering; Roche Genentech
FX This research was supported by the National Institutes of Health (grant
HHSN261200800001E).; R.J. No relevant conflicts of interest to disclose.
L. P. No relevant conflicts of interest to disclose. J.N. No relevant
conflicts of interest to disclose. D. G. No relevant conflicts of
interest to disclose. L. S. No relevant conflicts of interest to
disclose. S.N.H. No relevant conflicts of interest to disclose. C. H. No
relevant conflicts of interest to disclose. M. W. Financial activities
related to the present article: none to disclose. Financial activities
not related to the present article: grants/grants pending to institution
from GE Healthcare, Philips Healthcare, NIH. Other relationships: none
to disclose. R. R. C. No relevant conflicts of interest to disclose.
J.K. No relevant conflicts of interest to disclose. J.F. No relevant
conflicts of interest to disclose. D.J.B. No relevant conflicts of
interest to disclose. C.J. No relevant conflicts of interest to
disclose. T. M. Financial activities related to the present article:
none to disclose. Financial activities not related to the present
article: consultancy for Merck Schering and Roche Genentech; payment for
lectures including service on speakers' bureaus for Merck Schering and
Roche Genentech; payment for development of educational presentations
from Merck Schering. Other relationships: none to disclose.
NR 22
TC 48
Z9 50
U1 0
U2 5
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD APR
PY 2013
VL 267
IS 1
BP 212
EP 220
DI 10.1148/radiol.12120846
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 112AX
UT WOS:000316565000022
PM 23238158
ER
PT J
AU Rockey, SJ
AF Rockey, Sally J.
TI POLICING ETHICS
SO SCIENTIFIC AMERICAN
LA English
DT Letter
C1 NIH, Bethesda, MD 20892 USA.
RP Rockey, SJ (reprint author), NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0036-8733
J9 SCI AM
JI Sci.Am.
PD APR
PY 2013
VL 308
IS 4
BP 8
EP 8
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 111KB
UT WOS:000316519100002
ER
PT J
AU Kerrin, A
Weldon, S
Chung, AHK
Craig, T
Simpson, AJ
O'Kane, CM
McAuley, DF
Taggart, CC
AF Kerrin, Aoife
Weldon, Sinead
Chung, Allen Hung-Kang
Craig, Thelma
Simpson, A. John
O'Kane, Cecilia M.
McAuley, Danny Francis
Taggart, Clifford C.
TI Proteolytic cleavage of elafin by 20S proteasome may contribute to
inflammation in acute lung injury
SO THORAX
LA English
DT Article
ID ELASTASE-SPECIFIC INHIBITOR; RESPIRATORY-DISTRESS-SYNDROME; LEUKOCYTE
PROTEINASE-INHIBITOR; NEUTROPHIL ELASTASE; EPITHELIAL-CELLS; BACTERIAL
LIPOPOLYSACCHARIDE; CYSTIC-FIBROSIS; PRE-ELAFIN; EXPRESSION; DEGRADATION
AB Rationale We hypothesise that elafin levels in acute lung injury (ALI) decrease over time due, in part, to proteolytic degradation as observed in other lung diseases.
Objectives The aim of this study was to characterise temporal changes in elafin concentration in patients with ALI and to evaluate whether a decrease in elafin levels is due to elevated protease activity.
Methods Bronchoalveolar lavage fluid (BALF) was obtained from patients with ALI within 48 h of onset of ALI (day 0), at day 3 and at day 7. Elafin levels were quantified by ELISA. Elafin susceptibility to proteolytic cleavage by ALI BALF was assessed by Western blot and by high-performance liquid chromatography-mass spectrometry.
Measurements and main results Elafin levels were found to be significantly increased at the onset of ALI compared with healthy volunteers and fell significantly by day 7 compared with day 0. In contrast, levels of secretory leukocyte protease inhibitor did not decrease over time. This decrease in elafin was due to cleavage by the 20S proteasome which was significantly increased in ALI BALF. Incubation of ALI BALF with the proteasome inhibitor epoxomicin confirmed that 20S proteasome protease activity was responsible for proteolytic cleavage of elafin, resulting in diminished anti-elastase activity. In addition, free neutrophil elastase activity significantly increased in ALI BALF from day 0 to day 7.
Conclusions Elafin concentrations fall within the pulmonary compartment over the course of ALI as a result of proteolytic degradation. This loss of elafin may predispose people, in part, to excessive inflammation in ALI.
C1 [Kerrin, Aoife; Weldon, Sinead; Craig, Thelma; O'Kane, Cecilia M.; McAuley, Danny Francis; Taggart, Clifford C.] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Infect & Immun, Belfast BT9 7BL, Antrim, North Ireland.
[Chung, Allen Hung-Kang] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
[Simpson, A. John] Univ Newcastle, Inst Cellular Med, Newcastle, NSW 2300, Australia.
RP Taggart, CC (reprint author), Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Infect & Immun, Hlth Sci Bldg,97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland.
EM c.taggart@qub.ac.uk
RI Taggart, Clifford/G-4492-2014; Weldon, Sinead/J-5451-2014
OI Weldon, Sinead/0000-0001-5628-6624
FU Intramural Research Program of the National Heart, Lung, and Blood
Institute; Northern Ireland Chest Heart and Stroke Association [200941];
HSC Research and Development; Critical Care Translational Research
Group; Department of Education and Learning and Sir Jules Thorn
Charitable Trust
FX Northern Ireland Chest Heart and Stroke Association (200941), HSC
Research and Development, the Critical Care Translational Research
Group, Critical Care Translational Research Group, Department of
Education and Learning and Sir Jules Thorn Charitable Trust (AJS). This
research was supported by the Intramural Research Program of the
National Heart, Lung, and Blood Institute (AHKC).
NR 37
TC 5
Z9 5
U1 0
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0040-6376
J9 THORAX
JI Thorax
PD APR
PY 2013
VL 68
IS 4
BP 315
EP 321
DI 10.1136/thoraxjnl-2012-202536
PG 7
WC Respiratory System
SC Respiratory System
GA 103WO
UT WOS:000315950400004
PM 23242946
ER
PT J
AU Kappen, C
Yaworsky, PJ
Muller, YL
Salbaum, JM
AF Kappen, Claudia
Yaworsky, Paul J.
Muller, Yunhua L.
Salbaum, J. Michael
TI Transgenic studies on homeobox genes in nervous system development:
spina bifida in Isl1 transgenic mice
SO TRANSGENIC RESEARCH
LA English
DT Article
DE Binary transgenic system; Transactivator; VP16; Hox genes; Hoxd4; Hoxc8;
Isl1; Motorneurons; Ventral neural tube; Mesoderm; Cell proliferation;
Pbx1; Transcriptional target; Spina bifida; Neural tube closure
ID STEM-CELLS; HOX GENE; HOMEOTIC TRANSFORMATIONS; DIFFERENTIAL DISPLAY;
REGULATORY ELEMENTS; EXPRESSION PATTERN; PARAXIAL MESODERM; RESPONSE
ELEMENT; BINDING-PROTEIN; AXIAL SKELETON
AB To develop in vivo assays for homeobox gene function in neural development, we generated transgenic mice in which the expression of a homeobox gene is altered only within the nervous system, in neurons or neuronal precursor cells. Transgenic expression of Hoxc8 did not result in gross abnormalities, while a Hoxd4 transgene caused death shortly after birth. In neural progenitor cells, the motorneuron-specific homeodomain transcription factor Isl1 induced early developmental defects, including absence of anterior neural structures, profound defects in the neuroepithelium and defective neural tube closure. A fraction of Isl1 transgenic mice exhibited spina bifida. Isl1 transgene expression was also associated with decreased proliferation and increased Pbx1 expression in the ventral neural tube. Our results suggest a function for some homeobox genes in development of the nervous system, and that cell-type- and region-specific transgenic models will be useful to identify the cellular and molecular targets of homeobox transcription factors in nervous system development.
C1 [Kappen, Claudia] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Dept Dev Biol, Baton Rouge, LA 70810 USA.
[Yaworsky, Paul J.] Pfizer Res Technol Ctr, Cambridge, MA 02140 USA.
[Muller, Yunhua L.] Natl Inst Diabet & Kidney Dis, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ 85004 USA.
[Salbaum, J. Michael] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Lab Regulat Gene Express, Baton Rouge, LA 70810 USA.
RP Kappen, C (reprint author), Louisiana State Univ Syst, Pennington Biomed Res Ctr, Dept Dev Biol, 6400 Perkins Rd, Baton Rouge, LA 70810 USA.
EM claudia.kappen@pbrc.edu; Paul.Yaworsky@pfizer.com; ymuller@mail.nih.gov;
michael.salbaum@pbrc.edu
FU Arizona Disease Control Research Commission; Mayo Foundation for Medical
Education and Research; Neurosciences Support Corporation; R. Lounsbery
Foundation; University of Nebraska Research Initiative; Peggy M.
Pennington Cole Chair for Maternal Biology; NIH [RO1-HD34706,
RO1-HD055528]
FX We are grateful to Drs. Andy McMahon for providing the rat nestin
enhancer, Thomas Edlund for the Isl1 cDNA, Gerry Byrne for the IE-Hoxc8
and NFL-TSV plasmids, MiMi Macias for making the IE-Hoxd4 and IE-Isl1
constructs, to her and Dr. H. (Tina) Dinh Treece for performing RT-PCR
assays, to Diane Costanzo, Scott Hanson, and Jacalyn Mac-Gowan for
genotyping of transgenic mice, to Anita Jennings for histology, to Tom
Bargar for electron microscopy, and to Drs. David Gardner, Y. Gloria
Yueh, and Gabriela Pavlinkova for discussions. The initial transgenic
mouse strains were generated at Mayo Clinic Scottsdale, and additional
analyses performed at University of Nebraska Medical Center and
Pennington Biomedical Research Center. Portions of this work were
supported by the Arizona Disease Control Research Commission and Mayo
Foundation for Medical Education and Research (to C. K.), The
Neurosciences Support Corporation and the R. Lounsbery Foundation (to
J.M.S.), the University of Nebraska Research Initiative (to C. K. and
J.M.S.), the Peggy M. Pennington Cole Chair for Maternal Biology (to C.
K.), and NIH grants RO1-HD34706 (to C. K., with a supplement to G. P.)
and RO1-HD055528 (to J.M.S.).
NR 76
TC 1
Z9 1
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-8819
J9 TRANSGENIC RES
JI Transgenic Res.
PD APR
PY 2013
VL 22
IS 2
BP 343
EP 358
DI 10.1007/s11248-012-9643-x
PG 16
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 105KE
UT WOS:000316065900007
PM 23054727
ER
PT J
AU Savman, K
Heyes, MP
Svedin, P
Karlsson, A
AF Savman, Karin
Heyes, Melvyn P.
Svedin, Pernilla
Karlsson, Anna
TI Microglia/Macrophage-Derived Inflammatory Mediators Galectin-3 and
Quinolinic Acid are Elevated in Cerebrospinal Fluid from Newborn Infants
After Birth Asphyxia
SO TRANSLATIONAL STROKE RESEARCH
LA English
DT Article
DE Hypoxic-ischemic brain injury; Microglia; Neonate; Cerebrospinal fluid
galectin-3; Quinolinic acid
ID ISCHEMIC BRAIN-INJURY; KYNURENINE PATHWAY METABOLISM; HYPOXIA-ISCHEMIA;
NEONATAL ENCEPHALOPATHY; MICROGLIAL CELLS; NEUROLOGICAL DISEASE;
CYTOKINE RESPONSE; CEREBRAL-PALSY; NADPH-OXIDASE; L-TRYPTOPHAN
AB Activation of microglia/macrophages is important in neonatal hypoxic-ischemic (HI) brain injury. Based on experimental studies, we identified macrophage/microglia-derived mediators with potential neurotoxic effects after neonatal HI and examined them in cerebrospinal fluid (CSF) from newborn infants after birth asphyxia. Galectin-3 is a novel inflammatory mediator produced by microglia/macrophages. Galectin-3 is chemotactic for inflammatory cells and activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase resulting in production and release of reactive oxygen species (ROS). Matrix metalloproteinase-9 (MMP-9) is a tissue-degrading protease expressed by activated microglia in the immature brain after HI. Both galectin-3 and MMP-9 contribute to brain injury in animal models for neonatal HI. Quinolinic acid (QUIN) is a neurotoxic N-methyl-d-aspartate (NMDA) receptor agonist also produced by activated microglia/macrophages. Galectin-3 and MMP-9 were measured by ELISA and QUIN by mass spectrometry. Asphyxiated infants (n = 20) had higher levels of galectin-3 (mean (SEM) 2.64 (0.43) ng/mL) and QUIN (335.42 (58.9) nM) than controls (n = 15) (1.36 (0.46) ng/mL and 116.56 (16.46) nM, respectively), p < 0.05 and p < 0.01. Infants with septic infections (n = 10) did not differ from controls. Asphyxiated infants with abnormal outcome had higher levels of galectin-3 (3.96 (0.67) ng/mL) than those with normal outcome (1.76 (0.32) ng/mL), p = 0.02, and the difference remained significant in the clinically relevant group of infants with moderate encephalopathy. MMP-9 was detected in few infants with no difference between groups. The potentially neurotoxic macrophage/microglia-derived mediators galectin-3 and QUIN are increased in CSF after birth asphyxia and could serve as markers and may contribute to injury.
C1 [Savman, Karin] Univ Gothenburg, Perinatal Ctr, Dept Pediat, Sahlgrenska Acad, S-41685 Gothenburg, Sweden.
[Savman, Karin; Svedin, Pernilla] Univ Gothenburg, Dept Neurosci & Physiol, Sahlgrenska Acad, S-41685 Gothenburg, Sweden.
[Heyes, Melvyn P.] NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA.
[Karlsson, Anna] Univ Gothenburg, Dept Rheumatol & Inflammat Res, Inst Med, Sahlgrenska Acad, S-41346 Gothenburg, Sweden.
[Savman, Karin] Queen Silvia Childrens Hosp, Perinatal Ctr, S-41685 Gothenburg, Sweden.
RP Savman, K (reprint author), Queen Silvia Childrens Hosp, Perinatal Ctr, S-41685 Gothenburg, Sweden.
EM karin.savman@pediat.gu.se
FU Frimurar-Barnhus Foundation; Wilhelm and Martina Lundgren Foundation;
Linnea and Josef Carlsson Foundation; Jerring Foundation; Goteborg
Medical Society; Gustaf the Vth 80-Year Foundation
FX This work was supported by the Frimurar-Barnhus Foundation, the Wilhelm
and Martina Lundgren Foundation, Linnea and Josef Carlsson Foundation,
The Jerring Foundation, Goteborg Medical Society, and the Gustaf the Vth
80-Year Foundation.
NR 56
TC 13
Z9 14
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1868-4483
J9 TRANSL STROKE RES
JI Transl. Stroke Res.
PD APR
PY 2013
VL 4
IS 2
BP 228
EP 235
DI 10.1007/s12975-012-0216-3
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 109WB
UT WOS:000316399200011
PM 23807898
ER
PT J
AU Benninghoff, J
Rauh, W
Brantl, V
Schloesser, RJ
Moessner, R
Moller, HJ
Rujescu, D
AF Benninghoff, Jens
Rauh, Werner
Brantl, Victor
Schloesser, Robert J.
Moessner, Rainald
Moeller, Hans-Juergen
Rujescu, Dan
TI Cholinergic impact on neuroplasticity drives muscarinic M1 receptor
mediated differentiation into neurons
SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Biological psychiatry; dementia; pharmacotherapy; neuroplasticity;
acetylcholine
ID ADULT HIPPOCAMPAL NEUROGENESIS; PRECURSOR CELL-PROLIFERATION;
EPIDERMAL-GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; NEURAL STEM-CELLS;
ALZHEIMERS-DISEASE; RAT HIPPOCAMPUS; DENTATE GYRUS;
ACETYLCHOLINE-RELEASE; PROGENITOR CELLS
AB Objectives. Increasing evidence indicates that canonical neurotransmitters act as regulatory signals during neuroplasticity. Here, we report that muscarinic cholinergic neurotransmission stimulates differentiation of adult neural stem cells in vitro. Methods. Adult neural stem cells (ANSC) dissociated from the adult mouse hippocampus were expanded in culture with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Results. Carbachol (CCh), an analog of acetylcholine (ACh) significantly enhanced de novo differentiation into neurons on bFGF-and EGF-deprived stem cells as shown by the percentage of TUJ1 positive cells. By contrast, pirenzepine (PIR), a muscarinic M1 receptor antagonist, reduced the generation of neurons. Conclusion. Activation of cholinergic signaling drives the de novo differentiation of uncommitted stem cells into neurons. These effects appear to be predominantly mediated via the muscarinic M1 receptor subtype.
C1 [Benninghoff, Jens; Rauh, Werner; Brantl, Victor; Moeller, Hans-Juergen; Rujescu, Dan] LMU Univ Munich, Dept Psychiat, Munich, Germany.
[Schloesser, Robert J.] NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Programm, NIH, Bethesda, MD 20892 USA.
[Moessner, Rainald] Univ Bonn, Dept Psychiat, Bonn, Germany.
RP Benninghoff, J (reprint author), Dept Psychiat, Nussbaumstr 7, D-80336 Munich, Germany.
EM jens.benninghoff@med.uni-muenchen.de
NR 50
TC 2
Z9 2
U1 1
U2 7
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1562-2975
J9 WORLD J BIOL PSYCHIA
JI World J. Biol. Psychiatry
PD APR
PY 2013
VL 14
IS 3
BP 241
EP 246
DI 10.3109/15622975.2011.624121
PG 6
WC Psychiatry
SC Psychiatry
GA 109FL
UT WOS:000316351700006
PM 22022845
ER
PT J
AU Yuan, ZX
Rapoport, SI
Soldin, SJ
Remaley, AT
Taha, AY
Kellom, M
Gu, JH
Sampson, M
Ramsden, CE
AF Yuan, Zhi-Xin
Rapoport, Stanley I.
Soldin, Steven J.
Remaley, Alan T.
Taha, Ameer Y.
Kellom, Matthew
Gu, Jianghong
Sampson, Maureen
Ramsden, Christopher E.
TI Identification and profiling of targeted oxidized linoleic acid
metabolites in rat plasma by quadrupole time-of-flight mass spectrometry
SO BIOMEDICAL CHROMATOGRAPHY
LA English
DT Article
DE Q-TOFMS; hydroxy-octadecadienoic acid; oxo-octadecadienoic acid;
linoleic acid; rat plasma
ID LOW-DENSITY-LIPOPROTEIN; HYDROXY FATTY-ACIDS; LIPID-PEROXIDATION;
HYDROXYOCTADECADIENOIC ACID; ELECTROSPRAY-IONIZATION;
LIQUID-CHROMATOGRAPHY; OXIDATION-PRODUCTS; ARACHIDONIC-ACID; DISEASE;
BLOOD
AB Linoleic acid (LA) and LA-esters are the precursors of LA hydroperoxides, which are readily converted to 9- and 13-hydroxy-octadecadienoic acid (HODE) and 9- and 13-oxo-octadecadienoic acid (oxo ODE) metabolites in vivo. These four oxidized LA metabolites (OXLAMs) have been implicated in a variety of pathological conditions. Therefore, their accurate measurement may provide mechanistic insights into disease pathogenesis. Here we present a novel quadrupole time-of-flight mass spectrometry (Q-TOFMS) method for quantitation and identification of target OXLAMs in rat plasma. In this method, the esterified OXLAMs were base-hydrolyzed and followed by liquidliquid extraction. Quantitative analyses were based on one-point standard addition with isotope dilution. The Q-TOFMS data of target metabolites were acquired and multiple reaction monitoring extracted-ion chromatograms were generated post-acquisition with a 10ppm extraction window. The limit of quantitation was 9.735.9nmol/L depending on the metabolite. The method was reproducible with a coefficient of variation of <18.5%. Mean concentrations of target metabolites in rat plasma were 57.8, 123.2, 218.1 and 57.8nmol/L for 9-HODE, 13-HODE, 9-oxoODE and 13-oxoODE, respectively. Plasma levels of total OXLAMs were 456.9nmol/L, which correlated well with published concentrations obtained by gas chromatography/mass spectrometry (GC/MS). The concentrations were also obtained utilizing a standard addition curve approach. The calibration curves were linear with correlation coefficients of >0.991. Concentrations of 9-HODE, 13-HODE, 9-oxoODE and 13-oxoODE were 84.0, 138.6, 263.0 and 69.5nmol/L, respectively, which were consistent with the results obtained from one-point standard addition. Target metabolites were simultaneously characterized based on the accurate Q-TOFMS data. This is the first study of secondary LA metabolites using Q-TOFMS. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Yuan, Zhi-Xin; Rapoport, Stanley I.; Taha, Ameer Y.; Kellom, Matthew] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
[Ramsden, Christopher E.] NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
[Soldin, Steven J.; Remaley, Alan T.; Gu, Jianghong; Sampson, Maureen] NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Yuan, ZX (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
EM yuanz2@mail.nih.gov
FU National Institute on Aging, National Institute on Alcohol Abuse and
Alcoholism; Warren Grant Magnuson Clinical Center, National Institutes
of Health
FX No author has a conflict of interest with regard to this manuscript. The
research was supported by the intramural programs of the National
Institute on Aging, National Institute on Alcohol Abuse and Alcoholism,
and Warren Grant Magnuson Clinical Center, National Institutes of
Health.
NR 41
TC 5
Z9 5
U1 2
U2 35
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-3879
J9 BIOMED CHROMATOGR
JI Biomed. Chromatogr.
PD APR
PY 2013
VL 27
IS 4
BP 422
EP 432
DI 10.1002/bmc.2809
PG 11
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy
GA 103LV
UT WOS:000315919000003
PM 23037960
ER
PT J
AU Kovalchik, SA
AF Kovalchik, Stephanie A.
TI Aggregate-data estimation of an individual patient data linear random
effects meta-analysis with a patient covariate-treatment interaction
term
SO BIOSTATISTICS
LA English
DT Article
DE Clinical trials; Meta-analysis; Random effects models; Statistical
methods in Health service research
ID META-REGRESSION; SUBGROUP ANALYSES; LEVEL DATA; TRIALS; HETEROGENEITY;
STATISTICS; VARIANCE
AB Individual patient-data meta-analysis of randomized controlled trials is the gold standard for investigating how patient factors modify the effectiveness of treatment. Because participant data from primary studies might not be available, reliable alternatives using published data are needed. In this paper, I show that the maximum likelihood estimates of a participant-level linear random effects meta-analysis with a patient covariate-treatment interaction can be determined exactly from aggregate data when the model's variance components are known. I provide an equivalent aggregate-data EM algorithm and supporting software with the R package for the estimation of the "interaction meta-analysis" when the variance components are unknown. The properties of the methodology are assessed with simulation studies. The usefulness of the methods is illustrated with analyses of the effect modification of cholesterol and age on pravastatin in the multicenter placebo-controlled regression growth evaluation statin study. When a participant-level meta-analysis cannot be performed, aggregate-data interaction meta-analysis is a useful alternative for exploring individual-level sources of treatment effect heterogeneity.
C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
RP Kovalchik, SA (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8047, Rockville, MD 20892 USA.
EM kovalchiksa@mail.nih.gov
FU NIH/NCI
FX This research was supported by the intramural research program of the
NIH/NCI.
NR 27
TC 4
Z9 4
U1 1
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
J9 BIOSTATISTICS
JI Biostatistics
PD APR
PY 2013
VL 14
IS 2
BP 273
EP 283
DI 10.1093/biostatistics/kxs035
PG 11
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 106FC
UT WOS:000316127100006
PM 23001065
ER
PT J
AU Pfeiffer, RM
AF Pfeiffer, Ruth M.
TI Extensions of criteria for evaluating risk prediction models for public
health applications
SO BIOSTATISTICS
LA English
DT Article
DE Area under the receiver operator characteristics curve (ROC); AUC;
Discrimination; Discriminatory accuracy; Risk models; Study design
ID PROSTATE-CANCER; SUSCEPTIBILITY; CURVE
AB We recently proposed two novel criteria to assess the usefulness of risk prediction models for public health applications. The proportion of cases followed, PCF(p), is the proportion of individuals who will develop disease who are included in the proportion p of individuals in the population at highest risk. The proportion needed to follow-up, PNF(q), is the proportion of the general population at highest risk that one needs to follow in order that a proportion q of those destined to become cases will be followed (Pfeiffer, R.M. and Gail, M.H., 2011. Two criteria for evaluating risk prediction models. Biometrics 67, 1057-1065). Here, we extend these criteria in two ways. First, we introduce two new criteria by integrating PCF and PNF over a range of values of q or p to obtain iPCF, the integrated PCF, and iPNF, the integrated PNF. A key assumption in the previous work was that the risk model is well calibrated. This assumption also underlies novel estimates of iPCF and iPNF based on observed risks in a population alone. The second extension is to propose and study estimates of PCF, PNF, iPCF, and iPNF that are consistent even if the risk models are not well calibrated. These new estimates are obtained from case-control data when the outcome prevalence in the population is known, and from cohort data, with baseline covariates and observed health outcomes. We study the efficiency of the various estimates and propose and compare tests for comparing two risk models, both of which were evaluated in the same validation data.
C1 NIH, Biostat Branch, Bethesda, MD 20892 USA.
RP Pfeiffer, RM (reprint author), NIH, Biostat Branch, Bldg 10, Bethesda, MD 20892 USA.
EM pfeiffer@mail.nih.gov
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute
FX Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute.
NR 15
TC 1
Z9 2
U1 1
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
EI 1468-4357
J9 BIOSTATISTICS
JI Biostatistics
PD APR
PY 2013
VL 14
IS 2
BP 366
EP 381
DI 10.1093/biostatistics/kxs037
PG 16
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 106FC
UT WOS:000316127100013
PM 23087412
ER
PT J
AU Chen, F
Wang, Z
Bhattacharyya, T
AF Chen, Foster
Wang, Zhong
Bhattacharyya, Timothy
TI Convergence of Outcomes for Hip Fracture Fixation by Nails and Plates
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID TROCHANTERIC FRACTURES; INTERTROCHANTERIC FRACTURES; INTRAMEDULLARY
NAIL; GAMMA-NAIL; SCREW; ADOPTION; TRIAL; FEMUR
AB Recent popularity of intramedullary nails over sliding hip screws for treatment of intertrochanteric fractures is concerning given the absence of evidence for clinical superiority for nailing yet the presence of reimbursement differences.
We describe the change in outcomes of both procedures across a 15-year span and address the role of reimbursements in the setting of shifting patterns in use.
A 5% sample of Medicare enrollees from 1993 to 2007 was used. Cohorts were generated along diagnostic and procedure codes. Trends in device use by hospital type, surgical times, and rate of revision surgeries were compared. Historic reimbursements were examined.
Since 2005, intramedullary nail fixation has become the more common treatment in government, nonprofit, and for-profit hospitals. Before 1999, intramedullary nailing required 36 minutes longer to perform than plate-and-screw fixation on average, and had higher revision surgery rates (hazard ratio, 2.48; CI, 1.37-4.48) and 1-year mortality (hazard ratio, 1.42; CI, 1.01-1.99). These differences were not significant since 2000. Reimbursement differences have been consistently in favor of intramedullary nails.
Intramedullary nailing of intertrochanteric fractures has become as safe and efficient as the sliding hip screws, but has been more popular since 2006. Reimbursements were favorable for intramedullary nails in times of low and high use. These results argue against the reimbursement difference as the sole driving force for use of intramedullary nails.
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
C1 [Chen, Foster] Univ Calif San Diego, San Diego Sch Med, La Jolla, CA 92093 USA.
[Chen, Foster; Wang, Zhong; Bhattacharyya, Timothy] NIH, Bethesda, MD 20892 USA.
RP Bhattacharyya, T (reprint author), NIH, 10 Ctr Dr,Mail Code 1468, Bethesda, MD 20892 USA.
EM timothy.bhattacharyya@nih.gov
FU Clinical Research Training Program; National Institutes of Health (NIH);
Pfizer Inc; National Institute of Arthritis and Musculoskeletal and Skin
Diseases of the NIH
FX One or more of the authors (FC) has received funding from the Clinical
Research Training Program, a research program made possible through a
public-private partnership supported jointly by the National Institutes
of Health (NIH) and Pfizer Inc (through a grant to the Foundation for
NIH from Pfizer Inc). One or more of the authors (FC, ZW, TB) also were
supported in part by the Intramural Research Program of the National
Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH.
NR 19
TC 3
Z9 4
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD APR
PY 2013
VL 471
IS 4
BP 1349
EP 1355
DI 10.1007/s11999-012-2694-8
PG 7
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 097YW
UT WOS:000315510400044
PM 23184670
ER
PT J
AU Graves, JP
Edin, ML
Bradbury, JA
Gruzdev, A
Cheng, J
Lih, FB
Masinde, TA
Qu, W
Clayton, NP
Morrison, JP
Tomer, KB
Zeldin, DC
AF Graves, Joan P.
Edin, Matthew L.
Bradbury, J. Alyce
Gruzdev, Artiom
Cheng, Jennifer
Lih, Fred B.
Masinde, Tiwanda A.
Qu, Wei
Clayton, Natasha P.
Morrison, James P.
Tomer, Kenneth B.
Zeldin, Darryl C.
TI Characterization of Four New Mouse Cytochrome P450 Enzymes of the CYP2J
Subfamily
SO DRUG METABOLISM AND DISPOSITION
LA English
DT Article
ID ARACHIDONIC-ACID EPOXYGENASE; SOLUBLE EPOXIDE HYDROLASE;
ISCHEMIA-REPERFUSION INJURY; EPOXYEICOSATRIENOIC ACIDS;
MOLECULAR-CLONING; FUNCTIONAL-SIGNIFICANCE; HYPERPOLARIZING FACTORS;
LIVER MICROSOMES; CDNA CLONING; MICE LACKING
AB The cytochrome P450 superfamily encompasses a diverse group of enzymes that catalyze the oxidation of various substrates. The mouse CYP2J subfamily includes members that have wide tissue distribution and are active in the metabolism of arachidonic acid (AA), linoleic acid (LA), and other lipids and xenobiotics. The mouse Cyp2j locus contains seven genes and three pseudogenes located in a contiguous 0.62 megabase cluster on chromosome 4. We describe four new mouse CYP2J isoforms (designated CYP2J8, CYP2J11, CYP2J12, and CYP2J13). The four cDNAs contain open reading frames that encode polypeptides with 62-84% identity with the three previously identified mouse CYP2Js. All four new CYP2J proteins were expressed in Sf21 insect cells. Each recombinant protein metabolized AA and LA to epoxides and hydroxy derivatives. Specific antibodies, mRNA probes, and polymerase chain reaction primer sets were developed for each mouse CYP2J to examine their tissue distribution. CYP2J8 transcripts were found in the kidney, liver, and brain, and protein expression was confirmed in the kidney and brain (neuropil). CYP2J11 transcripts were most abundant in the kidney and heart, with protein detected primarily in the kidney (proximal convoluted tubules), liver, and heart (cardiomyocytes). CYP2J12 transcripts were prominently present in the brain, and CYP2J13 transcripts were detected in multiple tissues, with the highest expression in the kidney. CYP2J12 and CYP2J13 protein expression could not be determined because the antibodies developed were not immunospecific. We conclude that the four new CYP2J isoforms might be involved in the metabolism of AA and LA to bioactive lipids in mouse hepatic and extrahepatic tissues.
C1 [Graves, Joan P.; Edin, Matthew L.; Bradbury, J. Alyce; Gruzdev, Artiom; Cheng, Jennifer; Zeldin, Darryl C.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Lih, Fred B.; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Masinde, Tiwanda A.; Clayton, Natasha P.] NIEHS, Cellular & Mol Pathol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Qu, Wei] NIEHS, Natl Toxicol Program Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Morrison, James P.] Pathol Associates Inc, Charles River Labs, Durham, NC USA.
RP Zeldin, DC (reprint author), NIEHS, NIH, 111 TW Alexander Dr,Bldg 101,Room A214, Res Triangle Pk, NC 27709 USA.
EM zeldin@niehs.nih.gov
RI Tomer, Kenneth/E-8018-2013;
OI Edin, Matthew/0000-0002-7042-500X
FU Intramural Research Program of the National Institutes of Health
National Institute of Environmental Health Sciences [Z01 ES025034]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health National Institute of Environmental Health
Sciences [Grant Z01 ES025034].
NR 48
TC 8
Z9 10
U1 0
U2 8
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0090-9556
J9 DRUG METAB DISPOS
JI Drug Metab. Dispos.
PD APR
PY 2013
VL 41
IS 4
BP 763
EP 773
DI 10.1124/dmd.112.049429
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 105XM
UT WOS:000316106000012
PM 23315644
ER
PT J
AU Abrudan, J
Ramalho-Ortigao, M
O'Neil, S
Stayback, G
Wadsworth, M
Bernard, M
Shoue, D
Emrich, S
Lawyer, P
Kamhawi, S
Rowton, ED
Lehane, MJ
Bates, PA
Valenzeula, JG
Tomlinson, C
Appelbaum, E
Moeller, D
Thiesing, B
Dillon, R
Clifton, S
Lobo, NF
Wilson, RK
Collins, FH
McDowell, MA
AF Abrudan, J.
Ramalho-Ortigao, M.
O'Neil, S.
Stayback, G.
Wadsworth, M.
Bernard, M.
Shoue, D.
Emrich, S.
Lawyer, P.
Kamhawi, S.
Rowton, E. D.
Lehane, M. J.
Bates, P. A.
Valenzeula, J. G.
Tomlinson, C.
Appelbaum, E.
Moeller, D.
Thiesing, B.
Dillon, R.
Clifton, S.
Lobo, N. F.
Wilson, R. K.
Collins, F. H.
McDowell, M. A.
TI The characterization of the Phlebotomus papatasi transcriptome
SO INSECT MOLECULAR BIOLOGY
LA English
DT Review
DE sand fly; phebotomine; transcriptome
ID PROPHENOLOXIDASE-ACTIVATING SYSTEM; MOSQUITO ANOPHELES-GAMBIAE; INNATE
IMMUNE-RESPONSE; BETA-1,3-GLUCAN RECOGNITION PROTEIN; MULTIPLE SEQUENCE
ALIGNMENT; LUTZOMYIA-LONGIPALPIS; AEDES-AEGYPTI;
DROSOPHILA-MELANOGASTER; PERITROPHIC MATRIX; BOMBYX-MORI
AB As important vectors of human disease, phlebotomine sand flies are of global significance to human health, transmitting several emerging and re-emerging infectious diseases. The most devastating of the sand fly transmitted infections are the leishmaniases, causing significant mortality and morbidity in both the Old and New World. Here we present the first global transcriptome analysis of the Old World vector of cutaneous leishmaniasis, Phlebotomus papatasi (Scopoli) and compare this transcriptome to that of the New World vector of visceral leishmaniasis, Lutzomyia longipalpis. A normalized cDNA library was constructed using pooled mRNA from Phlebotomus papatasi larvae, pupae, adult males and females fed sugar, blood, or blood infected with Leishmania major. A total of 47615 generated sequences was cleaned and assembled into 17120 unique transcripts. Of the assembled sequences, 50% (8837 sequences) were classified using Gene Ontology (GO) terms. This collection of transcripts is comprehensive, as demonstrated by the high number of different GO categories. An in-depth analysis revealed 245 sequences with putative homology to proteins involved in blood and sugar digestion, immune response and peritrophic matrix formation. Twelve of the novel genes, including one trypsin, two peptidoglycan recognition proteins (PGRP) and nine chymotrypsins, have a higher expression level during larval stages. Two novel chymotrypsins and one novel PGRP are abundantly expressed upon blood feeding. This study will greatly improve the available genomic resources for P.papatasi and will provide essential information for annotation of the full genome.
C1 [Abrudan, J.; Ramalho-Ortigao, M.; Stayback, G.; Wadsworth, M.; Bernard, M.; Shoue, D.; Lobo, N. F.; Collins, F. H.; McDowell, M. A.] Univ Notre Dame, Dept Biol Sci, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.
[O'Neil, S.; Emrich, S.] Univ Notre Dame, Notre Dame, IN 46556 USA.
[Lawyer, P.] NIAID, Intracellular Parasite Biol Sect, Parasit Dis Lab, NIH, Rockville, MD USA.
[Kamhawi, S.; Valenzeula, J. G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Rowton, E. D.] Walter Reed Army Inst Res, Entomol Program, Silver Spring, MD USA.
[Lehane, M. J.] Univ Liverpool, Liverpool Sch Trop Med, Vector Grp, Liverpool L3 5QA, Merseyside, England.
[Bates, P. A.; Dillon, R.] Univ Lancaster, Div Biomed & Life Sci, Fac Hlth & Med, Lancaster, England.
[Tomlinson, C.; Appelbaum, E.; Moeller, D.; Thiesing, B.; Clifton, S.; Wilson, R. K.] Washington Univ, Genome Inst, St Louis, MO USA.
RP McDowell, MA (reprint author), Univ Notre Dame, Dept Biol Sci, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.
EM mcdowell.11@nd.edu
OI Bates, Paul/0000-0001-6861-5421; Dillon, Rod/0000-0002-3551-0030
FU National Human Genome Research Institute; Defense Advanced Research
Projects Agency [W911NF0410380]; Telemedicine and Advanced Technology
Research Center [W81XWH-10-1-0085]; VectorBase [NIH/NIAID
HHSN72200900039C]; NSF MRI Grant [DBI-0420980]
FX This project was supported by the National Human Genome Research
Institute and in part by an award from the Defense Advanced Research
Projects Agency (#W911NF0410380) and Telemedicine and Advanced
Technology Research Center (#W81XWH-10-1-0085) to Mary Ann McDowell.
This project was also supported by VectorBase (NIH/NIAID
HHSN72200900039C. The assembly was performed on the Notre Dame
Biocomplexity Cluster (University of Notre Dame, Notre Dame, IN, USA)
supported in part by NSF MRI Grant No. DBI-0420980. BLAST searches were
performed on the Biocompute server at Notre Dame.
NR 109
TC 6
Z9 6
U1 1
U2 53
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0962-1075
J9 INSECT MOL BIOL
JI Insect Mol. Biol.
PD APR
PY 2013
VL 22
IS 2
BP 211
EP 232
DI 10.1111/imb.12015
PG 22
WC Biochemistry & Molecular Biology; Entomology
SC Biochemistry & Molecular Biology; Entomology
GA 102OO
UT WOS:000315854100007
PM 23398403
ER
PT J
AU Hueper, K
Parikh, MA
Prince, MR
Schoenfeld, C
Liu, C
Bluemke, DA
Dashnaw, SM
Goldstein, TA
Hoffman, EA
Lima, JA
Skrok, J
Zheng, J
Barr, RG
Vogel-Claussen, J
AF Hueper, Katja
Parikh, Megha A.
Prince, Martin R.
Schoenfeld, Christian
Liu, Chia
Bluemke, David A.
Dashnaw, Stephen M.
Goldstein, Thomas A.
Hoffman, Eric A.
Lima, Joao A.
Skrok, Jan
Zheng, Jie
Barr, R. Graham
Vogel-Claussen, Jens
TI Quantitative and Semiquantitative Measures of Regional Pulmonary
Microvascular Perfusion by Magnetic Resonance Imaging and Their
Relationships to Global Lung Perfusion and Lung Diffusing Capacity The
Multiethnic Study of Atherosclerosis Chronic Obstructive Pulmonary
Disease Study
SO INVESTIGATIVE RADIOLOGY
LA English
DT Article
DE pulmonary microvascular blood flow; chronic obstructive pulmonary
disease (COPD); dynamic contrast-enhanced MRI; quantitative perfusion
maps; lung diffusing capacity
ID BLOOD-FLOW; REFERENCE VALUES; STANDARDIZATION; QUANTIFICATION; COPD;
SPIROMETRY; VOLUMES; SAMPLE; ADULTS; TIME
AB Objectives: The aim of this study was to evaluate the quantitative and semi-quantitative measures of regional pulmonary parenchymal perfusion in patients with chronic obstructive pulmonary disease (COPD) in relationship to global lung perfusion (GLP) and lung diffusing capacity (DLCO).
Materials and Methods: A total of 143 participants in the Multiethnic Study of Atherosclerosis COPD Study were examined by dynamic contrast-enhanced pulmonary perfusion magnetic resonance imaging (MRI) at 1.5 T. Pulmonary microvascular blood flow (PBF) was calculated on a pixel-by-pixel basis by using a dual-bolus technique and the Fermi function model. Semiquantitative parameters for regional pulmonary microvascular perfusion were calculated from signal intensity-time curves in the lung parenchyma. Intraoberserver and interobserver coefficients of variation (CVs) and correlations between quantitative and semiquantitative MRI parameters and with GLP and DLCO were determined.
Results: Quantitative and semiquantitative parameters of pulmonary microvascular perfusion were reproducible, with CVs for all parameters of less than 10%. Furthermore, these MRI parameters were correlated with GLP and DLCO, and there was good agreement between PBF and GLP. Quantitative and semiquantitative MRI parameters were closely correlated (eg, r = 0.86 for maximum signal increase with PBF). In participants without COPD, the physiological distribution of pulmonary perfusion could be determined by regional MRI measurements.
Conclusion: Regional pulmonary microvascular perfusion can reliably be quantified from dynamic contrast-enhanced MRI. Magnetic resonance imaging-derived quantitative and semiquantitative perfusion measures correlate with GLP and DLCO.
C1 [Hueper, Katja; Liu, Chia; Lima, Joao A.; Skrok, Jan; Vogel-Claussen, Jens] Johns Hopkins Univ, Baltimore, MD USA.
[Hueper, Katja; Schoenfeld, Christian; Vogel-Claussen, Jens] Hannover Med Sch, Biomed Res Endstage & Obstruct Lung Dis Hannover, D-30625 Hannover, Germany.
[Parikh, Megha A.; Prince, Martin R.; Dashnaw, Stephen M.; Barr, R. Graham] Columbia Univ, Med Ctr, New York, NY USA.
[Bluemke, David A.] NIH, Bethesda, MD 20892 USA.
[Goldstein, Thomas A.] Stanford Univ, Stanford, CA 94305 USA.
[Hoffman, Eric A.] Univ Iowa, Carver Coll Med, Iowa City, IA USA.
[Zheng, Jie] Washington Univ, Sch Med, St Louis, MO USA.
RP Vogel-Claussen, J (reprint author), Hannover Med Sch, Dept Radiol, Carl Neuberg Str 1, D-30625 Hannover, Germany.
EM vogel-claussen.jens@mh-hannover.de
RI Hueper, Katja/J-9566-2016; Prince, Martin/S-6850-2016
OI Hueper, Katja/0000-0002-3195-4400;
FU National Institutes of Health/National Heart Lung Blood Institute
[R01-HL093081, R01-HL077612, R01-HL075476, N01-HC95159-HC95169]
FX The Multiethnic Study of Atherosclerosis Chronic Obstructive Pulmonary
Disease Study was supported by the National Institutes of
Health/National Heart Lung Blood Institute R01-HL093081, R01-HL077612,
R01-HL075476, and N01-HC95159-HC95169.
NR 34
TC 15
Z9 15
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-9996
J9 INVEST RADIOL
JI Invest. Radiol.
PD APR
PY 2013
VL 48
IS 4
BP 223
EP 230
DI 10.1097/RLI.0b013e318281057d
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 105YQ
UT WOS:000316109000007
PM 23385398
ER
PT J
AU Shapiro, JM
Oyen, ML
AF Shapiro, Jenna M.
Oyen, Michelle L.
TI Hydrogel Composite Materials for Tissue Engineering Scaffolds
SO JOM
LA English
DT Article
ID DOUBLE NETWORK HYDROGELS; MESENCHYMAL STEM-CELLS; DONOR-SITE MORBIDITY;
MECHANICAL-PROPERTIES; CARTILAGE TISSUE; NUCLEUS PULPOSUS; ELECTROSPUN
SCAFFOLDS; OSTEOGENIC DIFFERENTIATION; BIOMEDICAL APPLICATIONS; COLLAGEN
NANOFIBERS
AB Hydrogels are appealing for biomaterials applications due to their compositional similarity with highly hydrated natural biological tissues. However, for structurally demanding tissue engineering applications, hydrogel use is limited by poor mechanical properties. Here, composite materials approaches are considered for improving hydrogel properties while attempting to more closely mimic natural biological tissue structures. A variety of composite material microstructures is explored, based on multiple hydrogel constituents, particle reinforcement, electrospun nanometer to micrometer diameter polymer fibers with single and multiple fiber networks, and combinations of these approaches to form fully three-dimensional fiber-reinforced hydrogels. Natural and synthetic polymers are examined for formation of a range of scaffolds and across a range of engineered tissue applications. Following a discussion of the design and fabrication of composite scaffolds, interactions between living biological cells and composite scaffolds are considered across the full life cycle of tissue engineering from scaffold fabrication to in vivo use. We conclude with a summary of progress in this area to date and make recommendations for continuing research and for advanced hydrogel scaffold development.
C1 [Shapiro, Jenna M.; Oyen, Michelle L.] Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England.
[Shapiro, Jenna M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Shapiro, JM (reprint author), Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England.
EM mlo29@cam.ac.uk
OI Oyen, Michelle/0000-0002-3428-748X
FU National Institutes of Health through the NIH-Cambridge Scholars Program
FX The authors acknowledge Daniel G.T. Strange for providing the SEM image
shown in Fig. 3b, Anne Bahnweg for assistance with SEM image collection,
and Matthew G. Rees for technical assistance. J.M.S. acknowledges
funding from the National Institutes of Health through the NIH-Cambridge
Scholars Program.
NR 111
TC 20
Z9 20
U1 3
U2 130
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1047-4838
J9 JOM-US
JI JOM
PD APR
PY 2013
VL 65
IS 4
BP 505
EP 516
DI 10.1007/s11837-013-0575-6
PG 12
WC Materials Science, Multidisciplinary; Metallurgy & Metallurgical
Engineering; Mineralogy; Mining & Mineral Processing
SC Materials Science; Metallurgy & Metallurgical Engineering; Mineralogy;
Mining & Mineral Processing
GA 105NO
UT WOS:000316078500007
ER
PT J
AU Redd, AD
Quinn, TC
AF Redd, Andrew D.
Quinn, Thomas C.
TI Phylogenetic Relatedness of HIV-1 Donor and Recipient Populations Reply
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Letter
C1 [Redd, Andrew D.; Quinn, Thomas C.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD USA.
RP Quinn, TC (reprint author), Johns Hopkins Univ, Sch Med, Rangos Bldg,Room 531,855 N Wolfe St, Baltimore, MD 21205 USA.
EM tquinn@jhmi.edu
NR 2
TC 0
Z9 0
U1 0
U2 2
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 APR 1
PY 2013
VL 207
IS 7
BP 1182
EP 1183
DI 10.1093/infdis/jit022
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 099SX
UT WOS:000315643100021
PM 23315325
ER
PT J
AU Mahar, JE
Bok, K
Green, KY
Kirkwood, CD
AF Mahar, Jackie E.
Bok, Karin
Green, Kim Y.
Kirkwood, Carl D.
TI The Importance of Intergenic Recombination in Norovirus GII.3 Evolution
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID NORWALK-LIKE VIRUSES; BLOOD GROUP ANTIGENS; ACUTE GASTROENTERITIS; HUMAN
CALICIVIRUSES; MOLECULAR EPIDEMIOLOGY; MAXIMUM-LIKELIHOOD;
MITOCHONDRIAL-DNA; GENETIC DIVERSITY; GII-4 NOROVIRUS; CAPSID PROTEIN
AB Norovirus genotype II.3 (GII.3) strains are a major cause of sporadic gastroenteritis. Intergenic recombination between the capsid and RNA-dependent RNA polymerase (RdRp) genes is common and results in the acquisition of an alternative RdRp genotype. This study aimed to explore the evolution of the GII. 3 capsid gene, focusing on the influence of intergenic recombination. The capsid genes from six GII. 3 norovirus strains, collected from Australian children between 2001 and 2010, were sequenced and aligned with 66 GII. 3 capsid sequences from GenBank, spanning 1975 to 2010. The GII. 3 capsid gene evolved at a rate of 4.16 x 10(-3) to 6.97 x 10(-3) nucleotide substitutions/site/year from 1975 to 2010 and clustered into five temporally sequential lineages. Clustering of the GII. 3 capsid gene sequences was associated with intergenic recombination and switches between RdRp genotypes GII.3, GII.a, GII.b, GII.12, and an undefined ancestral RdRp. Comparison of the substitution rate of the GII. 3 and GII.b RdRps suggested that RdRp switching allows a higher evolutionary rate, leading to increased genetic diversity and adaptability. Alignment of GII. 3 capsid sequences revealed 36 lineage-specific conserved amino acid substitutions, four of which were under positive selection. Many conserved substitutions were within predicted antibody binding regions and close to host attachment factor binding sites. In conclusion, evolution of GII. 3 noroviruses was primarily driven by intergenic recombination. The acquisition of new RdRps may lead to a faster mutation rate and increased genetic diversity, improving overall GII. 3 fitness.
C1 [Mahar, Jackie E.; Kirkwood, Carl D.] Royal Childrens Hosp, Enter Virus Grp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia.
[Mahar, Jackie E.; Kirkwood, Carl D.] La Trobe Univ, Dept Microbiol, Bundoora, Vic 3083, Australia.
[Bok, Karin; Green, Kim Y.] NIAID, Caliciviruses Sect, Infect Dis Lab, NIH,DHHS, Bethesda, MD 20892 USA.
RP Mahar, JE (reprint author), Royal Childrens Hosp, Enter Virus Grp, Murdoch Childrens Res Inst, Flemington Rd, Parkville, Vic 3052, Australia.
EM jemahar@students.latrobe.edu.au; carl.kirkwood@mcri.edu.au
FU Victorian Government's Operational Infrastructure Support Program;
Intramural Research Program of the NIH, NIAID
FX This study was supported by the Victorian Government's Operational
Infrastructure Support Program and the Intramural Research Program of
the NIH, NIAID.
NR 71
TC 19
Z9 23
U1 0
U2 6
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 APR
PY 2013
VL 87
IS 7
BP 3687
EP 3698
DI 10.1128/JVI.03056-12
PG 12
WC Virology
SC Virology
GA 103ZC
UT WOS:000315957100007
PM 23325692
ER
PT J
AU Matsuno, K
Weisend, C
da Rosa, APAT
Anzick, SL
Dahlstrom, E
Porcella, SF
Dorward, DW
Yu, XJ
Tesh, RB
Ebihara, H
AF Matsuno, Keita
Weisend, Carla
da Rosa, Amelia P. A. Travassos
Anzick, Sarah L.
Dahlstrom, Eric
Porcella, Stephen F.
Dorward, David W.
Yu, Xue-Jie
Tesh, Robert B.
Ebihara, Hideki
TI Characterization of the Bhanja Serogroup Viruses (Bunyaviridae): a Novel
Species of the Genus Phlebovirus and Its Relationship with Other
Emerging Tick-Borne Phleboviruses
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID M-SEGMENT REASSORTMENT; GENETIC-CHARACTERIZATION; NUCLEOCAPSID PROTEIN;
UUKUNIEMI-VIRUS; ANTIGENIC GROUP; PALMA VIRUS; PUNTA-TORO; FEVER; RNA;
SEQUENCE
AB Bhanja virus (BHAV) and its antigenically close relatives Forecariah virus (FORV), Kismayo virus (KISV), and Palma virus (PALV) are thought to be members of the family Bunyaviridae, but they have not been assigned to a genus or species. Despite their broad geographical distribution and reports that BHAV causes sporadic cases of febrile illness and encephalitis in humans, the public health importance of the Bhanja serogroup viruses remains unclear, due in part to the lack of sequence and biochemical information for the virus proteins. In order to better define the molecular characteristics of this group, we determined the full-length sequences of the L, M, and S genome segments of multiple isolates of BHAV as well as FORV and PALV. The genome structures of these Bhanja viruses are similar to those of viruses belonging to the genus Phlebovirus. Functional domains and amino acid motifs in the viral proteins that are conserved among other known phleboviruses were also identified in proteins of the BHAV group. Phylogenetic and serological analyses revealed that the BHAVs are most closely related to the novel emerging tick-borne phleboviruses severe fever with thrombocytopenia syndrome virus and Heartland virus, which have recently been implicated as causing severe acute febrile illnesses associated with thrombocytopenia in humans in China and the United States. Our results indicate that the Bhanja serogroup viruses constitute a single novel species in the genus Phlebovirus. The results of this study should facilitate epidemiological surveillance for other, similar tick-borne phleboviruses that may represent unrecognized causes of febrile illness in humans.
C1 [Matsuno, Keita; Weisend, Carla; Ebihara, Hideki] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
[Anzick, Sarah L.; Dahlstrom, Eric; Porcella, Stephen F.; Dorward, David W.] NIAID, Res Technol Branch, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
[da Rosa, Amelia P. A. Travassos; Yu, Xue-Jie; Tesh, Robert B.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
[Yu, Xue-Jie; Tesh, Robert B.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA.
RP Ebihara, H (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
EM ebiharah@niaid.nih.gov
FU Intramural Research Program of the NIH; NIH
[HHSN272201000040I/HHSN27200004/D4]
FX This work was supported by the Intramural Research Program of the NIH.
A.P.A.T.D.R., X.-J.Y., and R.B.T. were supported by NIH contract
HHSN272201000040I/HHSN27200004/D4.
NR 54
TC 34
Z9 40
U1 4
U2 23
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 APR
PY 2013
VL 87
IS 7
BP 3719
EP 3728
DI 10.1128/JVI.02845-12
PG 10
WC Virology
SC Virology
GA 103ZC
UT WOS:000315957100010
PM 23325688
ER
PT J
AU Day, PM
Thompson, CD
Schowalter, RM
Lowy, DR
Schiller, JT
AF Day, Patricia M.
Thompson, Cynthia D.
Schowalter, Rachel M.
Lowy, Douglas R.
Schiller, John T.
TI Identification of a Role for the trans-Golgi Network in Human
Papillomavirus 16 Pseudovirus Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID DYNEIN LIGHT-CHAIN; MINOR CAPSID PROTEIN; VIRUS-LIKE PARTICLES; SORTING
NEXIN 17; BREFELDIN-A; IN-VITRO; RETROGRADE TRANSPORT; LYSOSOME
BIOGENESIS; TYPE-16 INFECTION; DEPENDENT PATHWAY
AB Human papillomavirus 16 (HPV16) enters its host cells by a process that most closely resembles macropinocytosis. Uncoating occurs during passage through the endosomal compartment, and the low pH encountered in this environment is essential for infection. Furin cleavage of the minor capsid protein, L2, and cyclophilin B-mediated separation of L2 and the viral genome from the major capsid protein, L1, are necessary for escape from the late endosome (LE). Following this exodus, L2 and the genome are found colocalized at the ND10 nuclear subdomain, which is essential for efficient pseudogenome expression. However, the route by which L2 and the genome traverse the intervening cytoplasm between these two subcellular compartments has not been determined. This study extends our understanding of this phase in PV entry in demonstrating the involvement of the Golgi complex. With confocal microscopic analyses involving 5-ethynyl-2'-deoxyuridine (EdU)-labeled pseudogenomes and antibodies to virion and cellular proteins, we found that the viral pseudogenome and L2 travel to the trans-Golgi network (TGN) following exit from the LE, while L1 is retained. This transit is dependent upon furin cleavage of L2 and can be prevented pharmacologically with either brefeldin A or golgicide A, inhibitors of anterograde and retrograde Golgi trafficking. Additionally, Rab9a and Rab7b were determined to be mediators of this transit, as expression of dominant negative versions of these proteins, but not Rab7a, significantly inhibited HPV16 pseudovirus infection.
C1 [Day, Patricia M.; Thompson, Cynthia D.; Schowalter, Rachel M.; Lowy, Douglas R.; Schiller, John T.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
RP Day, PM (reprint author), NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
EM pmd@nih.gov
RI Kim, Seongman/N-6910-2014
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 54
TC 38
Z9 38
U1 0
U2 17
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 APR
PY 2013
VL 87
IS 7
BP 3862
EP 3870
DI 10.1128/JVI.03222-12
PG 9
WC Virology
SC Virology
GA 103ZC
UT WOS:000315957100023
PM 23345514
ER
PT J
AU Shao, HP
Calvo, KR
Gronborg, M
Tembhare, PR
Kreitman, RJ
Stetler-Stevenson, M
Yuan, CM
AF Shao, Haipeng
Calvo, Katherine R.
Groenborg, Marlene
Tembhare, Prashant R.
Kreitman, Robert J.
Stetler-Stevenson, Maryalice
Yuan, Constance M.
TI Distinguishing hairy cell leukemia variant from hairy cell leukemia:
Development and validation of diagnostic criteria
SO LEUKEMIA RESEARCH
LA English
DT Article
DE Hairy cell leukemia; Hairy cell leukemia variant; Flow cytometry;
Immunophenotype, HCL, HCL v, CD11c, CD25, CD103, CD123
ID RESIDUAL DISEASE DETECTION; FLOW-CYTOMETRY; LYMPHOPROLIFERATIVE
DISORDERS; IMMUNOPHENOTYPIC ANALYSIS; 2-CHLORODEOXYADENOSINE; CD123;
CHAIN; CLADRIBINE; EXPERIENCE; RITUXIMAB
AB Hairy cell leukemia (HCL) and hairy cell leukemia-variant (HCL-v) are rare diseases with overlapping clinico-pathological features. We performed flow cytometry analysis (FCM) of 213 cases (169 HCL, 35 HCL-v, 9 splenic marginal zone lymphoma (SMZL)), correlating results with available corresponding clinical and morphological data.
FCM distinguished HCL-v from HCL and SMZL based solely upon expression of four antigens (CD11c, CD25, CD103, CD123) combined with B-cell markers (CD19, CD20, CD22). HCL-v expressed bright CD20, bright CD22, CD11c(100%), CD103(100%), dim(40%) or negative(60%) CD123, and uniformly lacked CD25(100%). HCL expressed bright CD20, bright CD22, bright CD11c, bright CD25, CD103, and bright homogeneous CD123(100%). Aberrant expression of CD5(2%/3%), CD10(12%/3%), CD23(21%/11%), CD38(14%/0%), CD2(2%/9%), CD4(0.5%/0%) and CD13(0.5%/3%), was observed in HCL/HCL-v, respectively. SMZL cases were CD103(-) and CD123(-) except for one case with dim CD123. HCL showed significantly greater marrow infiltration over HCL-v. Prominent nucleoli were observed in most HCL-v but rarely in HCL. A third of HCL and HCL-v marrows were hypocellular or aplastic-appearing. Detection of BRAFV600E mutation and annexin A1 were examined in a subset of cases to further validate FCM diagnostic criteria. HCL-v was negative for both annexin A1 (100%) and BRAFV600E mutation (100%), in contrast to HCL (74% positive for annexin A1; 76% positive for BRAFV600E mutation).
HCL-v is resistant to traditional HCL therapy, making accurate diagnosis imperative. We have defined FCM criteria for differentiation of HCL-v from HCL and SMZL. Published by Elsevier Ltd.
C1 [Groenborg, Marlene; Tembhare, Prashant R.; Stetler-Stevenson, Maryalice; Yuan, Constance M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Calvo, Katherine R.] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Kreitman, Robert J.] NCI, Labs Mol Biol & Clin Pathol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Shao, Haipeng] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
RP Yuan, CM (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 2N108,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM yuanc@mail.nih.gov
RI Calvo, Katherine/A-8109-2009;
OI Calvo, Katherine/0000-0002-0771-4191
FU Intramural Research Program of the NIH, NCI
FX The authors wish to thank Catharine McCoy, Linda Weaver, Gregory Jasper,
and Christine Aguhar at the NCI flow cytometry laboratory for graciously
providing FCM access, and technical expertise. We are grateful to Jaime
Hahn for assistance with retrieving slides. This work was supported in
part by the Intramural Research Program of the NIH, NCI.
NR 39
TC 16
Z9 16
U1 0
U2 10
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 APR
PY 2013
VL 37
IS 4
BP 401
EP 409
DI 10.1016/j.leukres.2012.11.021
PG 9
WC Oncology; Hematology
SC Oncology; Hematology
GA 100ZN
UT WOS:000315744500010
PM 23347903
ER
PT J
AU Wu, M
LaGasse, LL
Wouldes, TA
Arria, AM
Wilcox, T
Derauf, C
Newman, E
Shah, R
Smith, LM
Neal, CR
Huestis, MA
DellaGrotta, S
Lester, BM
AF Wu, Min
LaGasse, Linda L.
Wouldes, Trecia A.
Arria, Amelia M.
Wilcox, Tara
Derauf, Chris
Newman, Elana
Shah, Rizwan
Smith, Lynne M.
Neal, Charles R.
Huestis, Marilyn A.
DellaGrotta, Sheri
Lester, Barry M.
TI Predictors of Inadequate Prenatal Care in Methamphetamine-Using Mothers
in New Zealand and the United States
SO MATERNAL AND CHILD HEALTH JOURNAL
LA English
DT Article
DE Methamphetamine; Adequate prenatal care; New Zealand; Kessner Index;
Child protective services
ID INNER-CITY WOMEN; NEW-YORK-CITY; DRUG-USE; PREGNANT-WOMEN;
HEALTH-INSURANCE; ANTENATAL CARE; LOW-INCOME; PSYCHOSOCIAL FACTORS;
BIRTH-WEIGHT; MEDICAL-CARE
AB This study compared patterns of prenatal care among mothers who used methamphetamine (MA) during pregnancy and non-using mothers in the US and New Zealand (NZ), and evaluated associations among maternal drug use, child protective services (CPS) referral, and inadequate prenatal care in both countries. The sample consisted of 182 mothers in the MA-Exposed and 196 in the Comparison groups in the US, and 107 mothers in the MA-Exposed and 112 in the Comparison groups in NZ. Positive toxicology results and/or maternal report of MA use during pregnancy were used to identify MA use. Information about sociodemographics, prenatal care and prenatal substance use was collected by maternal interview. MA-use during pregnancy is associated with lower socioeconomic status, single marital status, and CPS referral in both NZ and the US. Compared to their non-using counterparts, MA-using mothers in the US had significantly higher rates of inadequate prenatal care. No association was found between inadequate care and MA-use in NZ. In the US, inadequate prenatal care was associated with CPS referral, but not in NZ. Referral to CPS for drug use only composed 40 % of all referrals in the US, but only 15 % of referrals in NZ. In our study population, prenatal MA-use and CPS referral eclipse maternal sociodemographics in explanatory power for inadequate prenatal care. The predominant effect of CPS referral in the US is especially interesting, and should encourage further research on whether the US policy of mandatory reporting discourages drug-using mothers from seeking antenatal care.
C1 [Wu, Min; LaGasse, Linda L.; Wouldes, Trecia A.; DellaGrotta, Sheri; Lester, Barry M.] Brown Univ, Warren Alpert Med Sch, Brown Ctr Study Children Risk, Providence, RI 02912 USA.
[Wu, Min; LaGasse, Linda L.; Wouldes, Trecia A.; DellaGrotta, Sheri; Lester, Barry M.] Brown Univ, Women & Infants Hosp, Providence, RI USA.
[Wouldes, Trecia A.] Univ Auckland, Fac Med & Hlth Sci, Dept Psychol Med, Auckland 1, New Zealand.
[Arria, Amelia M.] Univ Maryland, Sch Publ Hlth, Ctr Young Adult Hlth & Dev, Family Sci Dept, College Pk, MD 20742 USA.
[Derauf, Chris; Neal, Charles R.] Univ Hawaii, John A Burns Sch Med, Dept Pediat, Honolulu, HI 96822 USA.
[Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA.
[Shah, Rizwan] Iowa Hlth, Blank Hosp Reg Child Protect Ctr, Des Moines, IA USA.
[Smith, Lynne M.] Harbor UCLA Med Ctr, LABioMed Inst, Dept Pediat, Los Angeles, CA USA.
[Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
RP Wu, M (reprint author), Brown Univ, Warren Alpert Med Sch, Brown Ctr Study Children Risk, Providence, RI 02912 USA.
EM min_wu@hms.harvard.edu
OI Arria, Amelia/0000-0002-6360-9265; Wouldes, Trecia/0000-0002-6609-8464
FU Intramural NIH HHS [ZIA DA000433-11, Z01 DA000433-09, ZIA DA000433-10,
Z01 DA000433-08, ZIA DA000433-12, ZIA DA000433-13]; NCATS NIH HHS [UL1
TR000124]; NIDA NIH HHS [R01 DA021757, R01DA021757, R01 DA014948]
NR 76
TC 3
Z9 3
U1 0
U2 5
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 APR
PY 2013
VL 17
IS 3
BP 566
EP 575
DI 10.1007/s10995-012-1033-8
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 104UN
UT WOS:000316021200023
PM 22588827
ER
PT J
AU Luke, JJ
Rubinstein, LV
Smith, GL
Ivy, SP
Harris, PJ
AF Luke, Jason J.
Rubinstein, Lawrence V.
Smith, Gary L.
Ivy, S. Percy
Harris, Pamela J.
TI Similar efficacy for phase I trials in comparison with DTIC for advanced
malignant melanoma: an analysis of melanoma outcomes in CTEP-sponsored
phase I trials 1995-2011
SO MELANOMA RESEARCH
LA English
DT Article
DE chemotherapy; CTEP; dacarbazine; melanoma; phase I
ID METASTATIC MELANOMA; CLINICAL-TRIALS; ONCOLOGY TRIALS; SOLID TUMORS;
CANCER; DACARBAZINE; SURVIVAL; THERAPY; ETHICS; TEMOZOLOMIDE
AB After ipilimumab, vemurafenib, and interleukin-2, standard of care chemotherapy for melanoma remains dacarbazine (response rate similar to 9%). Despite this, many physicians hesitate to refer patients to phase I protocols given a perceived lack of clinical benefit and potential for harm. To better understand the validity of these perceptions, the experience of all patients with melanoma treated on phase I trials sponsored by the National Cancer Institute-Cancer Therapy Evaluation Program (NCI-CTEP) from 1995 to 2011 were analyzed and compared with the pooled results of six contemporary phase III trials of dacarbazine. A total of 937 patients with melanoma were treated in 148 CTEP phase I trials. The majority were men with a median of two prior therapies (46% receiving prior dacarbazine). Response and clinical benefit rates in these trials were not clinically different from those of dacarbazine (phase I: 6.3 and 26.8% vs. dacarbazine: 8.8 and 27.9%) although grades 3 and 4 toxicity was significantly higher (54 vs. 28%). Efficacy and toxicity were generally consistent within phase I subgroups (targeted agents, immunotherapies, or chemotherapeutics) though targeted therapy was associated with a lower response rate, immunotherapy higher incidence of grade 4 toxicity. Thus, the perception of limited efficacy of phase I trials for patients with melanoma was disproven, whereas the perception of toxicity was observed. However, this difference in toxicity may have been largely because of the nature of phase I vs. phase III trials (i.e. more heavily pretreated) and because of the phase I trials often being multiagent as opposed to dacarbazine alone. Melanoma Res 23:152-158 (c) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Luke, Jason J.] Dana Farber Canc Inst, Melanoma Dis Ctr, Boston, MA 02215 USA.
[Rubinstein, Lawrence V.; Smith, Gary L.; Ivy, S. Percy; Harris, Pamela J.] NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
RP Luke, JJ (reprint author), Dana Farber Canc Inst, Melanoma Dis Ctr, 450 Brookline Ave, Boston, MA 02215 USA.
EM jason_luke@dfci.harvard.edu
NR 29
TC 2
Z9 2
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0960-8931
J9 MELANOMA RES
JI Melanoma Res.
PD APR
PY 2013
VL 23
IS 2
BP 152
EP 158
DI 10.1097/CMR.0b013e32835f73b2
PG 7
WC Oncology; Dermatology; Medicine, Research & Experimental
SC Oncology; Dermatology; Research & Experimental Medicine
GA 101YM
UT WOS:000315810300009
PM 23411478
ER
PT J
AU Salum, GA
Mogg, K
Bradley, BP
Gadelha, A
Pan, P
Tamanaha, AC
Moriyama, T
Graeff-Martins, AS
Jarros, RB
Polanczyk, G
do Rosario, MC
Leibenluft, E
Rohde, LA
Manfro, GG
Pine, DS
AF Salum, G. A.
Mogg, K.
Bradley, B. P.
Gadelha, A.
Pan, P.
Tamanaha, A. C.
Moriyama, T.
Graeff-Martins, A. S.
Jarros, R. B.
Polanczyk, G.
do Rosario, M. C.
Leibenluft, E.
Rohde, L. A.
Manfro, G. G.
Pine, D. S.
TI Threat bias in attention orienting: evidence of specificity in a large
community-based study
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Anxiety; attention; cognition; emotion; phobias
ID GENERALIZED-ANXIETY-DISORDER; PREFRONTAL CORTEX ACTIVATION; COMMON
MENTAL-DISORDERS; ANGRY FACES; SELECTIVE ATTENTION; EMOTIONAL FACES;
ADOLESCENT PSYCHOPATHOLOGY; TIME-COURSE; CHILDREN; INFORMATION
AB Background. Preliminary research implicates threat-related attention biases in paediatric anxiety disorders. However, major questions exist concerning diagnostic specificity, effects of symptom-severity levels, and threat-stimulus exposure durations in attention paradigms. This study examines these issues in a large, community school-based sample.
Method. A total of 2046 children (ages 6-12 years) were assessed using the Development and Well Being Assessment (DAWBA), Childhood Behavior Checklist (CBCL) and dot-probe tasks. Children were classified based on presence or absence of 'fear-related' disorders, 'distress-related' disorders, and behavioural disorders. Two dot-probe tasks, which differed in stimulus exposure, assessed attention biases for happy-face and threat-face cues. The main analysis included 1774 children.
Results. For attention bias scores, a three-way interaction emerged among face-cue emotional valence, diagnostic group, and internalizing symptom severity (F=2.87, p<0.05). This interaction reflected different associations between internalizing symptom severity and threat-related attention bias across diagnostic groups. In children with no diagnosis (n=1411, mean difference=11.03, S.E.=3.47, df=1, p<0.001) and those with distress-related disorders (n=66, mean difference=10.63, S.E.=5.24, df=1, p<0.05), high internalizing symptoms predicted vigilance towards threat. However, in children with fear-related disorders (n=86, mean difference=-11.90, S.E.=5.94, df=1, p<0.05), high internalizing symptoms predicted an opposite tendency, manifesting as greater bias away from threat. These associations did not emerge in the behaviour-disorder group (n=211).
Conclusions. The association between internalizing symptoms and biased orienting varies with the nature of developmental psychopathology. Both the form and severity of psychopathology moderates threat-related attention biases in children.
C1 [Salum, G. A.; Jarros, R. B.; Rohde, L. A.; Manfro, G. G.] Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil.
[Mogg, K.; Bradley, B. P.] Univ Southampton, Southampton, Hants, England.
[Gadelha, A.; Pan, P.; Tamanaha, A. C.; Moriyama, T.; Graeff-Martins, A. S.; do Rosario, M. C.] Univ Fed Sao Paulo, Sao Paulo, Brazil.
[Moriyama, T.; Graeff-Martins, A. S.; Polanczyk, G.; Rohde, L. A.] Univ Sao Paulo, Sao Paulo, Brazil.
[Leibenluft, E.; Pine, D. S.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
RP Salum, GA (reprint author), Hosp Clin Porto Alegre, Ramiro Barcelos 2350,Room 2202, BR-90035003 Porto Alegre, RS, Brazil.
EM gsalumjr@gmail.com
RI Pan, Pedro/I-5167-2013; Rohde, Luis Augusto/A-6426-2008; Bradley,
Brendan/B-9724-2008; Polanczyk, Guilherme/C-2345-2012; Psiquiatria,
Inct/I-1060-2013; Mogg, Karin/C-1181-2008; Tamanaha, Ana
Carina/J-5942-2012; Graeff-Martins, Ana Soledade/K-1974-2012; Salum,
Giovanni/A-7849-2010
OI Pan, Pedro/0000-0002-1943-6520; Rohde, Luis Augusto/0000-0002-4552-4188;
Gadelha, Ary/0000-0002-0993-8017; Polanczyk,
Guilherme/0000-0003-2311-3289; Mogg, Karin/0000-0002-2738-7378; Bradley,
Brendan/0000-0003-2801-4271; Tamanaha, Ana Carina/0000-0001-9915-6299;
Salum, Giovanni/0000-0002-7537-7289
FU CNPq; CAPES; FAPESP; AstraZeneca; Eli Lilly; Janssen-Cilag; Novartis;
National Council for Scientific and Technological Development (CNPq,
Brazil); Abbott; Shire; FAPERGS; FIPEHCPA
FX We thank the children and families for their participation, which made
this research possible; the other members of the high-risk cohort
research team (Dr Euripedes Constantino Miguel, Dr Rodrigo
Affonseca-Bressan, Dr Pedro Gomes de Alvarenga and Dr Helena Brentani);
the collaborators for the neuropsychological evaluation (Bruno Sini
Scarpato, Sandra Lie Ribeiro do Valle and Carolina Araujo); Dr Robert
Goodman for his research support regarding the DAWBA instrument
procedures and Dr Bacy Fleitlich-Bilyk for her clinical supervision. We
also thank the NIMH Intramural Research Program. This work is supported
by the following Brazilian government agencies: CNPq, CAPES and FAPESP.;
Giovanni Abrahao Salum has received a CNPq sandwich Ph.D. scholarship
[sandwich period at National Institutes of Mental Health (NIMH)] and is
currently in receipt of a CAPES doctoral scholarship. Ary Gadelha is in
receipt of continuous medical education support from AstraZeneca, Eli
Lilly and Janssen-Cilag. Pedro Pan is in receipt of research support
from CNPq and CAPES and continuous medical education support from
AstraZeneca, Eli Lilly and Janssen-Cilag. Ana Carina Tamanaha is in
receipt of a post-doctoral fellowship from FAPESP. Tais Moriyama has
received a CNPq Ph.D. scholarship and is in receipt of continuous
medical education support from AstraZeneca, Eli Lilly and Janssen-Cilag.
Ana Soledade Graeff-Martins is in receipt of a post-doctoral fellowship
from CNPq. Guilherme Vanoni Polanczyk has served as a speaker and/or
consultant to Eli Lilly, Novartis, and Shire Pharmaceuticals, developed
educational material for Janssen-Cilag, and receives unrestricted
research support from Novartis and from the National Council for
Scientific and Technological Development (CNPq, Brazil). Maria Conceicao
do Rosario receives research support from Brazilian government
institutions (CNPQ) and has worked in the last 5 years as a speaker for
Novartis and Shire. Luis Augusto Rohde was on the speakers' bureau
and/or acted as consultant for Eli Lilly, Janssen-Cilag, Novartis and
Shire in the last 3 years (received less than US$10 000 per year, which
is less than 5% of L.A.R.'s gross income per year). L. A. R. also
received travel awards (air tickets and hotel costs) from Novartis and
Janssen-Cilag in 2010 for participation at two child psychiatric
meetings. The ADHD and Juvenile Bipolar Disorder Outpatient Programs
chaired by L. A. R. received unrestricted educational and research
support from the following pharmaceutical companies in the last 3 years;
Abbott, Eli Lilly, Janssen-Cilag, Novartis, and Shire. Gisele Gus Manfro
receives research support from Brazilian government institutions (CNPQ,
FAPERGS, FIPEHCPA).
NR 46
TC 47
Z9 47
U1 9
U2 47
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD APR
PY 2013
VL 43
IS 4
BP 733
EP 745
DI 10.1017/S0033291712001651
PG 13
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 105MB
UT WOS:000316073500006
PM 22850475
ER
PT J
AU Zustiak, SP
Wei, YQ
Leach, JB
AF Zustiak, Silviya P.
Wei, Yunqian
Leach, Jennie B.
TI Protein-Hydrogel Interactions in Tissue Engineering: Mechanisms and
Applications
SO TISSUE ENGINEERING PART B-REVIEWS
LA English
DT Review
ID ENDOTHELIAL GROWTH-FACTOR; POLY(ETHYLENE GLYCOL) HYDROGELS; SUBSEQUENT
TRIGGERED RELEASE; COLLAGEN-BASED COMPOSITE; NEURAL STEM-CELLS;
HYALURONIC-ACID; AFFINITY-BINDING; FACTOR DELIVERY; SURFACE
IMMOBILIZATION; ALGINATE BIOMATERIAL
AB Recent advances in our understanding of the sophistication of the cellular microenvironment and the dynamics of tissue remodeling during development, disease, and regeneration have increased our appreciation of the current challenges facing tissue engineering. As this appreciation advances, we are better equipped to approach problems in the biology and therapeutics of even more complex fields, such as stem cells and cancer. To aid in these studies, as well as the established areas of tissue engineering, including cardiovascular, musculoskeletal, and neural applications, biomaterials scientists have developed an extensive array of materials with specifically designed chemical, mechanical, and biological properties. Herein, we highlight an important topic within this area of biomaterials research, protein-hydrogel interactions. Due to inherent advantages of hydrated scaffolds for soft tissue engineering as well as specialized bioactivity of proteins and peptides, this field is well-posed to tackle major needs within emerging areas of tissue engineering. We provide an overview of the major modes of interactions between hydrogels and proteins (e.g., weak forces, covalent binding, affinity binding), examples of applications within growth factor delivery and three-dimensional scaffolds, and finally future directions within the area of hydrogel-protein interactions that will advance our ability to control the cell-biomaterial interface.
C1 [Zustiak, Silviya P.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Wei, Yunqian; Leach, Jennie B.] Univ Maryland, Dept Chem Biochem & Environm Engn, Baltimore, MD 21250 USA.
RP Leach, JB (reprint author), Univ Maryland, Dept Chem Biochem & Environm Engn, Eng 314,1000 Hilltop Circle, Baltimore, MD 21250 USA.
EM jleach@umbc.edu
FU Intramural Research Program of The Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH
FX We acknowledge NIH-NINDS R01NS065205 and funds from the Intramural
Research Program of The Eunice Kennedy Shriver National Institute of
Child Health and Human Development, NIH for supporting this work.
NR 134
TC 15
Z9 15
U1 7
U2 167
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3368
EI 1937-3376
J9 TISSUE ENG PART B-RE
JI Tissue Eng. Part B-Rev.
PD APR
PY 2013
VL 19
IS 2
BP 160
EP 171
DI 10.1089/ten.teb.2012.0458
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 099VS
UT WOS:000315651800006
PM 23150926
ER
PT J
AU Wolff, L
Bies, J
AF Wolff, Linda
Bies, Juraj
TI p15Ink4b Functions in determining hematopoietic cell fates: Implications
for its role as a tumor suppressor
SO BLOOD CELLS MOLECULES AND DISEASES
LA English
DT Article
DE Leukemia; Tumor suppressor; Hematopoiesis; Methylation; Immune
surveillance; Erythropoiesis
ID ACUTE MYELOID-LEUKEMIA; DENDRITIC CELLS; TRANSCRIPTION FACTORS; DNA
METHYLATION; POOR-PROGNOSIS; P15(INK4B); PU.1; INACTIVATION; GENES;
HYPERMETHYLATION
AB The p15Ink4b gene is frequently hypermethylated in myeloid neoplasia and has been demonstrated to be a tumor suppressor. Since it is a member of the INK4b family of cyclin-dependent kinase inhibitors, it was initially presumed that its loss in leukemic blasts caused a dysregulation of the cell cycle. However, animal model experiments over the last several years have produced a very different picture of how p15Ink4b functions in hematopoietic cells and how its loss contributes to myelodysplastic syndrome and myeloid leukemia. It is clear now, that in early hematopoietic progenitors, p15Ink4b functions outside of its canonical role as a cell cycle inhibitor. Its functions are involved in signal transduction and influence the development of erythroid, monocytic and dendritic cells. Published by Elsevier Inc.
C1 [Wolff, Linda; Bies, Juraj] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA.
RP Wolff, L (reprint author), NCI, Cellular Oncol Lab, Room 4124,37 Convent Dr, Bethesda, MD 20892 USA.
EM wolffl@mail.nih.gov; biesj@mail.nih.gov
FU National Cancer Institute, Center for Cancer Research, NIH
FX This work was supported by the intramural research program of the
National Cancer Institute, Center for Cancer Research, NIH
NR 43
TC 9
Z9 9
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1079-9796
EI 1096-0961
J9 BLOOD CELL MOL DIS
JI Blood Cells Mol. Dis.
PD APR
PY 2013
VL 50
IS 4
BP 227
EP 231
DI 10.1016/j.bcmd.2013.01.006
PG 5
WC Hematology
SC Hematology
GA AD8IE
UT WOS:000333508900001
PM 23403260
ER
PT J
AU Schairer, C
Soliman, AS
Omar, S
Khaled, H
Eissa, S
Ben Ayed, F
Khalafallah, S
Ben Ayoub, W
Kantor, ED
Merajver, S
Swain, SM
Gail, M
Brown, LM
AF Schairer, Catherine
Soliman, Amr S.
Omar, Sherif
Khaled, Hussein
Eissa, Saad
Ben Ayed, Farhat
Khalafallah, Samir
Ben Ayoub, Wided
Kantor, Elizabeth D.
Merajver, Sofia
Swain, Sandra M.
Gail, Mitchell
Brown, Linda Morris
TI Assessment of diagnosis of inflammatory breast cancer cases at two
cancer centers in Egypt and Tunisia
SO CANCER MEDICINE
LA English
DT Article
DE Edema; Egypt; erythema; inflammatory breast cancer; peau d'orange;
Tunisia
AB The diagnosis of inflammatory breast cancer (IBC) is largely clinical and therefore inherently somewhat subjective. The objective of this study was to evaluate the diagnosis of IBC at two centers in North Africa where a higher proportion of breast cancer is diagnosed as IBC than in the United States (U.S.). Physicians prospectively enrolled suspected IBC cases at the National Cancer Institute (NCI) - Cairo, Egypt, and the Institut Salah Azaiz (ISA), Tunisia, recorded extent and duration of signs/symptoms of IBC on standardized forms, and took digital photographs of the breast. After second-level review at study hospitals, photographs and clinical information for confirmed IBC cases were reviewed by two U.S. oncologists. We calculated percent agreement between study hospital and U.S. oncologist diagnoses. Among cases confirmed by at least one U.S. oncologist, we calculated median extent and duration of signs and Spearman correlations. At least one U.S. oncologist confirmed the IBC diagnosis for 69% (39/50) of cases with photographs at the NCI-Cairo and 88% (21/24) of cases at the ISA. All confirmed cases had at least one sign of IBC (erythema, edema, peau d'orange) that covered at least one-third of the breast. The median duration of signs ranged from 1 to 3 months; extent and duration of signs were not statistically significantly correlated. From the above-mentioned outcomes, it can be concluded that the diagnosis of a substantial proportion of IBC cases is unambiguous, but a subset is difficult to distinguish from other types of locally advanced breast cancer. Among confirmed cases, the extent of signs was not related to delay in diagnosis.
C1 [Schairer, Catherine; Gail, Mitchell; Brown, Linda Morris] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Soliman, Amr S.] Univ Nebraska, Med Ctr, Coll Publ Hlth, Dept Epidemiol, Omaha, NE 68198 USA.
[Omar, Sherif] Cairo Univ, Natl Canc Inst, Dept Surg, Cairo 11796, Egypt.
[Khaled, Hussein] Cairo Univ, Natl Canc Inst, Cairo 11796, Egypt.
[Eissa, Saad] Cairo Univ, Natl Canc Inst, Dept Pathol, Cairo 11796, Egypt.
[Ben Ayed, Farhat; Khalafallah, Samir; Ben Ayoub, Wided] Inst Salah Azaiz, Tunis 1006, Tunisia.
[Kantor, Elizabeth D.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
[Merajver, Sofia] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Swain, Sandra M.] Natl Naval Med Ctr, Med Oncol Branch, Bethesda, MD 20889 USA.
RP Schairer, C (reprint author), NCI, 6120 Execut Blvd,Rm 8026, Rockville, MD 20852 USA.
EM schairec@exchange.nih.gov
OI Kantor, Elizabeth/0000-0002-9124-5323; Swain, Sandra/0000-0002-1320-3830
FU National Cancer Institute
FX This study was supported by intramural funds from the National Cancer
Institute.
NR 19
TC 4
Z9 4
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2045-7634
J9 CANCER MED-US
JI Cancer Med.
PD APR
PY 2013
VL 2
IS 2
BP 178
EP 184
DI 10.1002/cam4.48
PG 7
WC Oncology
SC Oncology
GA V36KI
UT WOS:000209210600006
PM 23634285
ER
PT J
AU Towner, PH
AF Towner, Philip H.
TI The two letters to Timothy, The letter to Titus
SO CATHOLIC BIBLICAL QUARTERLY
LA English
DT Book Review
C1 [Towner, Philip H.] Amer Bible Soc, Nida Inst Bibl Scholarship, New York, NY 10023 USA.
RP Towner, PH (reprint author), Amer Bible Soc, Nida Inst Bibl Scholarship, New York, NY 10023 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU CATHOLIC BIBLICAL ASSOC AMER
PI WASHINGTON
PA CATHOLIC UNIV AMERICA, 620 MICHIGAN AVE, NE, WASHINGTON, DC 20064 USA
SN 0008-7912
EI 2163-2529
J9 CATH BIBLICAL QUART
JI Cathol. Biblic. Q.
PD APR
PY 2013
VL 75
IS 2
BP 360
EP 361
PG 2
WC Religion
SC Religion
GA V38OZ
UT WOS:000209354000023
ER
PT J
AU Wang, XS
AF Wang, Xiaosheng
TI Discovery of molecular associations among aging, stem cells, and cancer
based on gene expression profiling
SO CHINESE JOURNAL OF CANCER
LA English
DT Review
DE Cancer; aging; stem cells; gene expression profiling; cancer informatics
ID EMBRYONIC STEM; TRANSCRIPTIONAL NETWORK; KEY REGULATORS; HUMAN KIDNEY;
HUMAN MUSCLE; HUMAN SKIN; SIGNATURE; TUMORS; PLURIPOTENCY; DISEASES
AB The emergence of a huge volume of "omics". data enables a computational approach to the investigation of the biology of cancer. The cancer informatics approach is a useful supplement to the traditional experimental approach. I reviewed several reports that used a bioinformatics approach to analyze the associations among aging, stem cells, and cancer by microarray gene expression profiling. The high expression of aging- or human embryonic stem cell-related molecules in cancer suggests that certain important mechanisms are commonly underlying aging, stem cells, and cancer. These mechanisms are involved in cell cycle regulation, metabolic process, DNA damage response, apoptosis, p53 signaling pathway, immune/inflammatory response, and other processes, suggesting that cancer is a developmental and evolutional disease that is strongly related to aging. Moreover, these mechanisms demonstrate that the initiation, proliferation, and metastasis of cancer are associated with the deregulation of stem cells. These findings provide insights into the biology of cancer. Certainly, the findings that are obtained by the informatics approach should be justified by experimental validation. This review also noted that next-generation sequencing data provide enriched sources for cancer informatics study.
C1 NCI, Biometr Res Branch, NIH, Rockville, MD 20852 USA.
RP Wang, XS (reprint author), NCI, Biometr Res Branch, NIH, Rockville, MD 20852 USA.
EM xiaosheng.wang@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 47
TC 3
Z9 3
U1 2
U2 10
PU SUN YAT SEN UNIV MED SCI WHO
PI GUANGZHOU
PA 651 DONGFENG RD E, GUANGZHOU, GUANGDONG 510060, PEOPLES R CHINA
SN 1000-467X
EI 1944-446X
J9 CHIN J CANCER
JI Chin. J. Cancer
PD APR
PY 2013
VL 32
IS 4
BP 155
EP 161
DI 10.5732/cjc.012.10114
PG 7
WC Oncology
SC Oncology
GA AM1ZT
UT WOS:000339648500002
PM 23298462
ER
PT J
AU Uchida, N
Hanawa, H
Yamamoto, M
Shimada, T
AF Uchida, Naoya
Hanawa, Hideki
Yamamoto, Motoko
Shimada, Takashi
TI The Chicken Hypersensitivity Site 4 Core Insulator Blocks Promoter
Interference in Lentiviral Vectors
SO HUMAN GENE THERAPY METHODS
LA English
DT Article
ID HUMAN HEMATOPOIETIC-CELLS; TRANSGENE EXPRESSION; CHS4 INSULATOR;
GENE-THERAPY; INTERNAL PROMOTERS; RETROVIRAL VECTORS; IN-VIVO;
CHROMATIN; ACTIVATION; GENERATION
AB Lentiviral vectors, including double internal promoters, can be used to express two transgenes in a single vector construct; however, transcriptional activities from double internal promoters are often inhibited by promoter interference. To determine whether the chicken hypersensitivity site 4 insulator (cHS4) could block promoter interference, lentiviral vectors including an MSCV-U3 promoter (Mp) and an EF1 alpha promoter (Ep) were generated, and transgene expression was evaluated among transduced cells. In the Ep-Mp configuration, transcriptional activity from Mp was much lower, while Mp-Ep had similar transcription levels from both promoters. The cHS4 core insulator increased expression levels from Mp in HeLa cells, hematopoietic cell lines, and mouse peripheral blood cells following hematopoietic stem cell transplantation transduced with the Mp-Ep configured vector. This blocking function was mainly mediated by barrier activity regions in the insulator but not by CCCTC-binding factor (CTCF) binding sites. Cytosine-phosphate-guanine (CpG) methylation did not contribute to this barrier activity. In summary, combining the cHS4 insulator in double promoter vectors can improve transgene expression levels in various cell lines and mouse hematopoietic repopulating cells. These findings are useful for developing hematopoietic stem cell gene therapy.
C1 [Uchida, Naoya; Hanawa, Hideki; Yamamoto, Motoko; Shimada, Takashi] Nippon Med Sch, Tokyo 1138602, Japan.
[Uchida, Naoya] Nippon Med Sch, Dept Internal Med, Div Hematol, Tokyo 1138602, Japan.
[Uchida, Naoya] NIDDK, Mol & Clin Hematol, NHLBI, NIH, Bethesda, MD 20892 USA.
RP Uchida, N (reprint author), NIH, Mol & Clin Hematol Branch, 9000 Rockville Pike,Bldg 10,9N112, Bethesda, MD 20892 USA.
EM uchidan@nhlbi.nih.gov
FU NHLBI/NIDDK
FX We thank Drs. John Tisdale and Matthew Hsieh in Molecular and Clinical
Hematology Branch, National Heart Lung and Blood Institute
(NHLBI)/National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), National Institutes of Health for the preparation and editing
of our manuscript. This work was supported in part by the intramural
programs of NHLBI/NIDDK.
NR 24
TC 8
Z9 8
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1946-6536
EI 1946-6544
J9 HUM GENE THER METHOD
JI Hum. Gene Ther. Methods
PD APR
PY 2013
VL 24
IS 2
BP 117
EP 124
DI 10.1089/hgtb.2012.152
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI4LD
UT WOS:000336835900006
PM 23448496
ER
PT J
AU Rosenbaum, M
Ravussin, Y
Leibel, RL
AF Rosenbaum, Michael
Ravussin, Yann
Leibel, Rudolph L.
TI Does diet composition have structural consequences in the hypothalamus?
SO MOLECULAR METABOLISM
LA English
DT Editorial Material
C1 [Rosenbaum, Michael; Leibel, Rudolph L.] Columbia Univ Coll Phys & Surg, Dept Pediat, Div Mol Genet, 630 West 168th St, New York, NY 10032 USA.
[Ravussin, Yann] NIH, Bethesda, MD 20892 USA.
RP Leibel, RL (reprint author), Columbia Univ Coll Phys & Surg, Dept Pediat, Div Mol Genet, 630 West 168th St, New York, NY 10032 USA.
FU NCATS NIH HHS [UL1 TR000040]; NIDDK NIH HHS [R01 DK064773]
NR 9
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2212-8778
J9 MOL METAB
JI Mol. Metab.
PD APR
PY 2013
VL 2
IS 2
BP 58
EP 59
DI 10.1016/j.molmet.2013.01.005
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V42UC
UT WOS:000209637700002
PM 24199148
ER
PT J
AU Borges, IT
Shea, CD
Ohayon, J
Jones, BC
Stone, RD
Ostuni, J
Shiee, N
McFarland, H
Bielekova, B
Reich, DS
AF Borges, Isabela T.
Shea, Colin D.
Ohayon, Joan
Jones, Blake C.
Stone, Roger D.
Ostuni, John
Shiee, Navid
McFarland, Henry
Bielekova, Bibiana
Reich, Daniel S.
TI The effect of daclizumab on brain atrophy in relapsing-remitting
multiple sclerosis
SO MULTIPLE SCLEROSIS AND RELATED DISORDERS
LA English
DT Article
DE Multiple sclerosis; Brain atrophy; Gray matter; Brain volume;
Dactizumab; Interferon beta
AB Daclizumab is a monoclonal antibody that reduces inflammation in multiple sclerosis (MS). Through a retrospective analysis, our objective was to determine whether daclizumab treatment reduces the rate of brain structure atrophy in comparison to a mixture of other disease-modifying therapies (mainly different interferon beta preparations). We analyzed MRI examinations (1332 scans from 70 MS cases) obtained between 2000 and 2011 in a single center and processed with an automated brain segmentation method. We used mixed-effects multivariable linear regression models to determine whether a median of 4.3 years of daclizumab therapy in 26 patients altered rates of brain-volume change, controlling for variations in MRI protocol. The control group consisted of 44 patients not treated with daclizumab. We found that supratentorial brain volume declined by 5.17 ml per year (95% confidence limits: 3.58-6.77) off daclizumab therapy. On daclizumab, the annual rate of volume loss decreased to 3.72 ml (p=0.01). The rate of ventricular enlargement decreased from 1.26 to 0.42 ml per year (p<0.001). Focused analysis suggests that reduction in gray matter atrophy rate most likely underlies these results. In summary, in this retrospective analysis, daclizumab therapy substantially decreased the rate of brain atrophy in relapsing-remitting MS in comparison to other disease-modifying therapies, predominantly interferon beta. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Borges, Isabela T.; Shea, Colin D.; Ohayon, Joan; Jones, Blake C.; Stone, Roger D.; Ostuni, John; McFarland, Henry; Bielekova, Bibiana; Reich, Daniel S.] NINDS, NIH, Bethesda, MD 20892 USA.
[Shiee, Navid] NIH, Radiol & Imaging Sci Clin Ctr, Rochester, MN USA.
[Shiee, Navid] Henry M Jackson Fdn Adv Mil Med, Ctr Neurosci & Regenerat Med, Bethesda, MD USA.
RP Reich, DS (reprint author), NINDS, Translat Neuroradiol Unit, NIH, 10 Ctr Dr,MSC 1400,Bldg 10,Room 5C103, Bethesda, MD 20892 USA.
EM daniel.reich@nih.gov
OI Borges, Isabela/0000-0002-4208-8253
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke, National Institutes of Health
FX The Intramural Research Program of the National Institute of
Neurological Disorders and Stroke, National Institutes of Health,
supported all aspects of this study, including data acquisition and
analysis. There was no support from any industry sources.
NR 50
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Z9 15
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2211-0348
EI 2211-0356
J9 MULT SCLER RELAT DIS
JI Mult. Scler. Relat. Disord.
PD APR
PY 2013
VL 2
IS 2
BP 133
EP 140
DI 10.1016/j.msard.2012.10.002
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA V37LC
UT WOS:000209276300012
PM 23580931
ER
PT J
AU Kramer, M
Dees, C
Huang, JG
Schlottmann, I
Palumbo-Zerr, K
Zerr, P
Gelse, K
Beyer, C
Distler, A
Marquez, VE
Distler, O
Schett, G
Distler, JHW
AF Kraemer, Marlene
Dees, Clara
Huang, Jingang
Schlottmann, Inga
Palumbo-Zerr, Katrin
Zerr, Pawel
Gelse, Kolja
Beyer, Christian
Distler, Alfiya
Marquez, Victor E.
Distler, Oliver
Schett, Georg
Distler, Joerg H. W.
TI Inhibition of H3K27 histone trimethylation activates fibroblasts and
induces fibrosis
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Article
ID SYSTEMIC-SCLEROSIS; EXTRACELLULAR-MATRIX; SCLERODERMA FIBROBLASTS;
COLLAGEN EXPRESSION; T-CELLS; METHYLATION; DISEASE; EPIGENETICS;
MECHANISMS; PREVENTS
AB Objectives Epigenetic modifications such as DNA methylation and histone acetylation have been implicated in the pathogenesis of systemic sclerosis. However, histone methylation has not been investigated so far. We therefore aimed to evaluate the role of the trimethylation of histone H3 on lysine 27 (H3K27me3) on fibroblast activation and fibrosis.
Methods H3K27me3 was inhibited by 3-deazaneplanocin A (DZNep) in cultured fibroblasts and in two murine models of dermal fibrosis. Fibrosis was analysed by assessment of the dermal thickening, determination of the hydroxyproline content and by quantification of the numbers of myofibroblasts. The expression of fos-related antigen 2 (fra-2) was assessed by real-time PCR, western blot and immunohistochemistry and modulated by siRNA.
Results Inhibition of H3K27me3 stimulated the release of collagen in cultured fibroblasts in a time and dose-dependent manner. Treatment with DZNep exacerbated fibrosis induced by bleomycin or by overexpression of a constitutively active transforming growth factor beta receptor type I. Moreover, treatment with DZNep alone was sufficient to induce fibrosis. Inhibition of H3K27me3 induced the expression of the profibrotic transcription factor fra-2 in vitro and in vivo. Knockdown of fra-2 completely prevented the profibrotic effects of DZNep.
Conclusions These data demonstrate a novel role of H3 Lys27 histone methylation in fibrosis. In contrast to other epigenetic modifications such as DNA methylation and histone acetylation, H3 Lys27 histone methylation acts as a negative regulator of fibroblast activation in vitro and in vivo by repressing the expression of fra-2.
C1 [Kraemer, Marlene; Dees, Clara; Huang, Jingang; Schlottmann, Inga; Palumbo-Zerr, Katrin; Zerr, Pawel; Beyer, Christian; Distler, Alfiya; Schett, Georg; Distler, Joerg H. W.] Univ Erlangen Nurnberg, Dept Internal Med 3, D-91054 Erlangen, Germany.
[Kraemer, Marlene; Dees, Clara; Huang, Jingang; Schlottmann, Inga; Palumbo-Zerr, Katrin; Zerr, Pawel; Beyer, Christian; Distler, Alfiya; Schett, Georg; Distler, Joerg H. W.] Univ Erlangen Nurnberg, Inst Clin Immunol, D-91054 Erlangen, Germany.
[Gelse, Kolja] Univ Erlangen Nurnberg, Dept Orthopaed Trauma Surg, D-91054 Erlangen, Germany.
[Marquez, Victor E.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[Distler, Oliver] Univ Zurich Hosp, Ctr Expt Rheumatol, CH-8091 Zurich, Switzerland.
[Distler, Oliver] Univ Zurich Hosp, Zurich Ctr Integrat Human Physiol, CH-8091 Zurich, Switzerland.
RP Distler, JHW (reprint author), Univ Erlangen Nurnberg, Dept Internal Med 3, Ulmenweg 18, D-91054 Erlangen, Germany.
EM joerg.distler@uk-erlangen.de
OI Beyer, Christian/0000-0003-0319-662X
FU Deutsche Forschungsgesellschaft [DI 1537/1-1, DI 1537/2-1, DI 1537/4-1,
DI 1537/5-1, AK 144/1-1, SCHE 1583/7-1]; IZKF in Erlangen [A20, A40];
ELAN-Programme of the University of Erlangen-Nuremberg; Career Support
Award of Medicine of the Ernst Jung Foundation; Intramural Research
Programme of the NIH, National Cancer Institute, Center for Cancer
Research
FX This study was funded by grants DI 1537/1-1, DI 1537/2-1, DI 1537/4-1,
DI 1537/5-1, AK 144/1-1 and SCHE 1583/7-1 of the Deutsche
Forschungsgesellschaft, grants A20 and A40 of the IZKF in Erlangen, the
ELAN-Programme of the University of Erlangen-Nuremberg and the Career
Support Award of Medicine of the Ernst Jung Foundation. This research
was supported in part by the Intramural Research Programme of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 33
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U1 0
U2 16
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD APR
PY 2013
VL 72
IS 4
BP 614
EP 620
DI 10.1136/annrheumdis-2012-201615
PG 7
WC Rheumatology
SC Rheumatology
GA 096BJ
UT WOS:000315378500024
PM 22915621
ER
PT J
AU Andersen, DK
AF Andersen, Dana K.
TI Diabetes and cancer: placing the association in perspective
SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
LA English
DT Review
DE cancer; diabetes; metformin; obesity; pancreatic cancer; pancreatic
polypeptide; pancreatogenic diabetes
ID LIFE-STYLE INTERVENTION; POPULATION-BASED COHORT; PANCREATIC-CANCER;
GLUCOSE-METABOLISM; K-RAS; RISK; MELLITUS; METFORMIN; INSULIN; MORTALITY
AB Purpose of review
The association of diabetes and cancer has received increased attention as data have emerged to indicate that the type of diabetes treatment may influence the risk of cancer, and that the risk of cancer among diabetic individuals can be reduced by intervention. The association of diabetes and pancreatic cancer is particularly strong, but often misunderstood. Long-standing type 1 diabetes and type 2 diabetes increase the risk for this malignancy, but the cancer can also induce pancreatogenic, or type 3c, diabetes as well.
Recent findings
This review covers the recent findings which help to clarify these relationships, and offers guidance for prevention, early detection, and treatment. Obesity and, separately, diabetes increase the risk of several common malignancies by about two-fold. This risk is reduced by successful treatments. Type 3c diabetes is more common than previously realized, and strategies to differentiate type 3c diabetes from type 2 diabetes, to identify those candidates who will benefit from screening studies, are discussed.
Summary
The death rate because of pancreatic and other cancers can be reduced by an aggressive approach to reversing obesity and hyperinsulinemia, achieving good glycemic control in diabetic patients, and identifying at an early timepoint those patients with pancreatogenic diabetes.
C1 [Andersen, Dana K.] NIDDK, Clin Studies Program, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA.
RP Andersen, DK (reprint author), NIDDK, Div Digest Dis & Nutr, NIH, 2 Democracy Plaza,Room 659, Bethesda, MD 20892 USA.
EM andersendk@niddk.nih.gov
NR 53
TC 11
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U1 0
U2 19
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1752-296X
J9 CURR OPIN ENDOCRINOL
JI Curr. Opin. Endocrinol. Diabetes Obes.
PD APR
PY 2013
VL 20
IS 2
BP 81
EP 86
DI 10.1097/MED.0b013e32835eddd3
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 097ND
UT WOS:000315479900001
PM 23422245
ER
PT J
AU De Boeck, A
Pauwels, P
Hensen, K
Rummens, JL
Westbroek, W
Hendrix, A
Maynard, D
Denys, H
Lambein, K
Braems, G
Gespach, C
Bracke, M
De Wever, O
AF De Boeck, Astrid
Pauwels, Patrick
Hensen, Karen
Rummens, Jean-Luc
Westbroek, Wendy
Hendrix, An
Maynard, Dawn
Denys, Hannelore
Lambein, Kathleen
Braems, Geert
Gespach, Christian
Bracke, Marc
De Wever, Olivier
TI Bone marrow-derived mesenchymal stem cells promote colorectal cancer
progression through paracrine neuregulin 1/HER3 signalling
SO GUT
LA English
DT Article
ID HUMAN COLON-CANCER; GROWTH-FACTOR RECEPTOR; TUMOR MICROENVIRONMENT;
METASTATIC NICHE; ERBB RECEPTORS; TENASCIN-C; IN-VIVO; HEREGULIN;
KINASE; MYOFIBROBLASTS
AB Objective Bone marrow-derived mesenchymal stem cells (BM-MSC) migrate to primary tumours and drive tumour progression. This study aimed to identify the molecular mechanisms associated with these heterotypic cellular interactions and analyse their relevance in colorectal cancer (CRC).
Design Paracrine interactions of BM-MSC with CRC cells were studied using collagen invasion assays, cell counts, flow cytometric cell-cycle analysis and tumour xenograft models. The role of neuregulin 1 (NRG1) and the human epidermal growth factor receptor (HER) family pathways were investigated using tyrosine kinase assays, mass spectrometry, pharmacological inhibition, antibody-mediated neutralisation and RNA interference. Transmembrane neuregulin 1 (tNRG1), HER2 and HER3 expression was analysed in primary CRC (n = 54), adjacent normal colorectal tissues (n = 4), liver metastases (n = 3) and adjacent normal liver tissues (n = 3) by immunohistochemistry.
Results BM-MSC stimulate invasion, survival and tumorigenesis of CRC through the release of soluble NRG1, activating the HER2/HER3-dependent PI3K/AKT signalling cascade in CRC cells. Similarly, tumour-associated mesenchymal cells (T-MC) in CRC demonstrate high tNRG1 expression, which is significantly associated with advanced Union for International Cancer Control stage (p = 0.005) and invasion depth (p = 0.04) and decreased 5-year progression-free survival (p = 0.01). HER2 and HER3 show membrane localisation in cancer cells of CRC tissue.
Conclusion Paracrine NRG1/HER3 signals initiated by BM-MSC and T-MC promote CRC cell progression, and high tNRG1 expression is associated with poor prognosis in CRC.
C1 [De Boeck, Astrid; Hendrix, An; Bracke, Marc; De Wever, Olivier] Ghent Univ Hosp, Dept Radiat Oncol & Expt Canc Res, Lab Expt Canc Res, B-9000 Ghent, Belgium.
[Pauwels, Patrick] Univ Antwerp, Dept Pathol, Antwerp, Belgium.
[Hensen, Karen; Rummens, Jean-Luc] Jesse Hosp, Lab Expt Hematol, Hasselt, Belgium.
[Westbroek, Wendy; Maynard, Dawn] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[Hendrix, An; Denys, Hannelore] Ghent Univ Hosp, Dept Med Oncol, Ghent, Belgium.
[Lambein, Kathleen] Ghent Univ Hosp, Dept Pathol, Ghent, Belgium.
[Braems, Geert] Ghent Univ Hosp, Dept Gynaecol, Ghent, Belgium.
[Gespach, Christian] Univ Paris 06, INSERM, UMR Mol & Clin Oncol S938, Ctr Rech St Antoine, Paris, France.
RP De Wever, O (reprint author), Ghent Univ Hosp, Dept Radiat Oncol & Expt Canc Res, Lab Expt Canc Res, De Pintelaan 185, B-9000 Ghent, Belgium.
EM olivier.dewever@ugent.be
RI de wever, olivier/J-3094-2013
OI de wever, olivier/0000-0002-5453-760X
FU National Human Genome Research Institute; Centrum voor Gezwelziekten;
Flemish community and France [I.2007.03, T.2009.14, T.2010.14]; Vlaamse
Liga tegen Kanker, Stichting tegen Kanker; Bijzonder Onderzoeksfonds
UGent; ADB [1148408N]; Fund for Scientific Research-Flanders
FX This work was supported by the Intramural Research Program of the
National Human Genome Research Institute, Centrum voor Gezwelziekten,
the Scientific Exchange Program between the Flemish community and France
(I.2007.03, T.2009.14, T.2010.14), Vlaamse Liga tegen Kanker, Stichting
tegen Kanker, Bijzonder Onderzoeksfonds UGent, travel grant (AH and
ODW), a doctoral grant (ADB; 1148408N) and a postdoctoral researcher
(ODW) from the Fund for Scientific Research-Flanders.
NR 57
TC 52
Z9 52
U1 1
U2 30
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 APR
PY 2013
VL 62
IS 4
BP 550
EP 560
DI 10.1136/gutjnl-2011-301393
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 099CB
UT WOS:000315595800011
PM 22535374
ER
PT J
AU Leng, Y
Fessler, EB
Chuang, DM
AF Leng, Yan
Fessler, Emily Bame
Chuang, De-Maw
TI Neuroprotective effects of the mood stabilizer lamotrigine against
glutamate excitotoxicity: roles of chromatin remodelling and Bcl-2
induction
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Bcl-2; glutamate; histone deacetylase; lamotrigine; neuroprotection
ID HISTONE DEACETYLASE INHIBITION; GLYCOGEN-SYNTHASE KINASE-3; TRANSGENIC
MOUSE MODEL; VALPROIC ACID; BIPOLAR DISORDER; IN-VIVO;
CEREBRAL-ISCHEMIA; PROTEIN BCL-2; DOUBLE-BLIND; HUMAN BRAIN
AB Lamotrigine (LTG), a phenyltriazine derivative and anti-epileptic drug, has emerged as an effective first-line treatment for bipolar mood disorder. Like the other mood stabilizers lithium and valproate, LTG also has neuroprotective properties but its exact mechanisms remain poorly defined. The present study utilized rat cerebellar granule cells (CGCs) to examine the neuroprotective effects of LTG against glutamate-induced excitotoxicity and to investigate potential underlying mechanisms. CGCs pretreated with LTG were challenged with an excitotoxic dose of glutamate. Pretreatment caused a time-and concentration-dependent inhibition of glutamate excitotoxicity with nearly full protection at higher doses (>= 100 mu M), as revealed by cell viability assays and morphology. LTG treatment increased levels of acetylated histone H3 and H4 as well as dose-and time-dependently enhanced B-cell lymphoma-2 (Bcl-2) mRNA and protein levels; these changes were associated with up-regulation of the histone acetylation and activity of the Bcl-2 promoter. Importantly, lentiviral-mediated Bcl-2 silencing by shRNA reduced both LTG-induced Bcl-2 mRNA up-regulation and neuroprotection against glutamate excitotoxicity. Finally, the co-presence of a sub-effective concentration of LTG (10 mM) with lithium or valproate produced synergistic neuroprotection. Together, our results demonstrate that the neuroprotective effects of LTG against glutamate excitotoxicity likely involve histone deacetylase inhibition and downstream up-regulation of anti-apoptotic protein Bcl-2. These underlying mechanisms may contribute to the clinical efficacy of LTG in treating bipolar disorder and warrant further investigation.
C1 [Leng, Yan; Fessler, Emily Bame; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, 10 Ctr Dr,MSC1363, Bethesda, MD 20892 USA.
EM chuang@mail.nih.gov
FU NIMH, NIH; Hsu Family Foundation
FX This study was supported by the Intramural Research Program of NIMH, NIH
and a gift fund from the Hsu Family Foundation. The authors thank
members in the Molecular Neurobiology Section, NIMH, NIH, notably Dr
Chi-Tso Chiu, Dr Joshua Hunsberger and Peter Leeds, for their helpful
discussions and assistance.
NR 69
TC 14
Z9 15
U1 0
U2 9
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 APR
PY 2013
VL 16
IS 3
BP 607
EP 620
DI 10.1017/S1461145712000429
PG 14
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 098DX
UT WOS:000315527600011
PM 22564541
ER
PT J
AU Moya, PR
Wendland, JR
Salemme, J
Fried, RL
Murphy, DL
AF Moya, Pablo R.
Wendland, Jens R.
Salemme, Jennifer
Fried, Ruby L.
Murphy, Dennis L.
TI miR-15a and miR-16 regulate serotonin transporter expression in human
placental and rat brain raphe cells
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE miR-15a; miR-16; serotonin transporter; SERT; SLC6A4
ID OBSESSIVE-COMPULSIVE DISORDER; PROMOTER POLYMORPHISM; TARGET SITE; GENE;
ASSOCIATION; DEPRESSION; ACTIVATION; RECEPTORS; VARIANTS; LEUKEMIA
AB The serotonin transporter (SERT) is a key regulatory molecule in serotonergic transmission implicated in numerous biological processes relevant to human disorders. Recently, it was shown that SERT expression is controlled by miR-16 in mouse brain. Here, we show that SERT expression is regulated additionally by miR-15a as well as miR-16 in human and rat tissues. This post-transcriptional regulation was observed and characterized in reporter assays and likewise when endogenous SERT expression was evaluated in human placental choriocarcinoma JAR cells and rat brain raphe RN46A cells - two cell lines that endogenously express SERT. Similar effects for miR-16 to those of miR-15a were found in both human and rat cell lines. The effects of miR-15a and miR-16 were comparable in extent to those originally reported for miR-16 in mice. These findings represent a novel layer of complexity for SERT expression regulation exerted by the mir-15a/16 cluster, whose genes are adjacently located at human chromosome 13q14.3.
C1 [Moya, Pablo R.; Salemme, Jennifer; Fried, Ruby L.; Murphy, Dennis L.] NIMH, Clin Sci Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Wendland, Jens R.] F Hoffmann La Roche & Co Ltd, Pharma Res & Early Dev, CH-4002 Basel, Switzerland.
RP Moya, PR (reprint author), NIMH, Clin Sci Lab, 10-3D41,10 Ctr Dr, Bethesda, MD 20892 USA.
EM moyap@mail.nih.gov
FU National Institute of Mental Health, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health. The
authors also thank James Nagle and Debbie Kauffman, from the NINDS DNA
sequencing core facility, for outstanding technical assistance with
sequencing the SLC6A4 3'-UTR and reporter constructs, and Dr Scott R.
Whittemore, University of Louisville, for providing us with the RN46A
cell line.
NR 37
TC 15
Z9 19
U1 1
U2 8
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 APR
PY 2013
VL 16
IS 3
BP 621
EP 629
DI 10.1017/S1461145712000454
PG 9
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 098DX
UT WOS:000315527600012
PM 22564678
ER
PT J
AU Tao, MH
Marian, C
Shields, PG
Potischman, N
Nie, J
Krishnan, SS
Berry, DL
Kallakury, BV
Ambrosone, C
Edge, SB
Trevisan, M
Winston, J
Freudenheim, JL
AF Tao, M-H
Marian, C.
Shields, P. G.
Potischman, N.
Nie, J.
Krishnan, S. S.
Berry, D. L.
Kallakury, B. V.
Ambrosone, C.
Edge, S. B.
Trevisan, M.
Winston, J.
Freudenheim, J. L.
TI Exposures in early life: associations with DNA promoter methylation in
breast tumors
SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE
LA English
DT Article
DE breast cancer; early-life exposure; epidemiology; epigenetics; promoter
methylation
ID NEW-YORK EXPOSURES; CANCER-RISK; BIRTH-WEIGHT; SMOKE EXPOSURE;
BODY-MASS; METAANALYSIS; HYPERMETHYLATION; INFANCY; COHORT; MILK
AB There is evidence that epigenetic changes occur early in breast carcinogenesis. We hypothesized that early-life exposures associated with breast cancer would be associated with epigenetic alterations in breast tumors. In particular, we examined DNA methylation patterns in breast tumors in association with several early-life exposures in a population-based case-control study. Promoter methylation of E-cadherin, p16 and RAR-beta(2) genes was assessed in archived tumor blocks from 803 cases with real-time methylation-specific PCR. Unconditional logistic regression was used for case-case comparisons of those with and without promoter methylation. We found no differences in the prevalence of DNA methylation of the individual genes by age at menarche, age at first live birth and weight at age 20. In case-case comparisons of premenopausal breast cancer, lower birth weight was associated with increased likelihood of E-cadherin promoter methylation (OR = 2.79, 95% CI, 1.15-6.82, for <= 2.5 v. 2.6-2.9 kg); higher adult height with RAR-beta(2) methylation (OR = 3.34, 95% CI, 1.19-9.39, for >= 1.65 v. <1.60 m); and not having been breastfed with p16 methylation (OR = 2.75, 95% CI, 1.14-6.62). Among postmenopausal breast cancers, birth order was associated with increased likelihood of p16 promoter methylation. Being other than first in the birth order was inversely associated with likelihood of >= 1 of the three genes being methylated for premenopausal breast cancers, but positively associated with methylation in postmenopausal women. These results suggest that there may be alterations in methylation associated with early-life exposures that persist into adulthood and affect breast cancer risk.
C1 [Tao, M-H] Mt Sinai Sch Med, Inst Translat Epidemiol, New York, NY 10029 USA.
[Marian, C.; Shields, P. G.; Krishnan, S. S.] Ohio State Univ, Ctr Canc, Columbus, OH 43210 USA.
[Potischman, N.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Nie, J.; Trevisan, M.; Freudenheim, J. L.] SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14260 USA.
[Berry, D. L.; Kallakury, B. V.] Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA.
[Ambrosone, C.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Edge, S. B.] Roswell Pk Canc Inst, Dept Surg, Buffalo, NY 14263 USA.
[Trevisan, M.] CUNY, Sch Biomed Educ, New York, NY 10021 USA.
[Winston, J.] Potomac Hosp, Woodbridge, VA USA.
RP Tao, MH (reprint author), Mt Sinai Sch Med, Inst Translat Epidemiol, POB 1057, New York, NY 10029 USA.
EM menghua.tao@mssm.edu
RI Marian, Catalin/B-1750-2012;
OI Marian, Catalin/0000-0002-7749-1384
FU National Institute on Alcohol Abuse and Alcoholism [P50-AA09802];
Department of Defense [DAMD 179616202, DAMD 17030446]; National Cancer
Institute [R01CA 092040]
FX This study would not have been possible without the support of all the
study participants and the research staff of the WEB Study. This work
was supported in part by the National Institute on Alcohol Abuse and
Alcoholism (P50-AA09802), the Department of Defense (DAMD 179616202,
DAMD 17030446) and the National Cancer Institute (R01CA 092040).
NR 46
TC 1
Z9 1
U1 0
U2 11
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 2040-1744
J9 J DEV ORIG HLTH DIS
JI J. Dev. Orig. Health Dis.
PD APR
PY 2013
VL 4
IS 2
BP 182
EP 190
DI 10.1017/S2040174412000694
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 100GO
UT WOS:000315685800009
PM 25054684
ER
PT J
AU Cui, CH
Noronha, A
Morikawa, H
Alvarez, VA
Stuber, GD
Szumlinski, KK
Kash, TL
Roberto, M
Wilcox, MV
AF Cui, Changhai
Noronha, Antonio
Morikawa, Hitoshi
Alvarez, Veronica A.
Stuber, Garret D.
Szumlinski, Karen K.
Kash, Thomas L.
Roberto, Marisa
Wilcox, Mark V.
TI New insights on neurobiological mechanisms underlying alcohol addiction
SO NEUROPHARMACOLOGY
LA English
DT Review
DE Alcohol; Dependence; Addiction; Metaplasticity; CRF; VTA; BNST; mGluR;
Binge drinking; Dendritic spines
ID CORTICOTROPIN-RELEASING-FACTOR; VENTRAL TEGMENTAL AREA; LONG-TERM
POTENTIATION; CHRONIC ETHANOL-CONSUMPTION; MIDBRAIN DOPAMINE NEURONS;
EXCITATORY SYNAPTIC-TRANSMISSION; DENDRITIC SPINE MORPHOLOGY;
AMINOBUTYRIC-ACID RELEASE; IN-THE-DARK; STRIA TERMINALIS
AB Alcohol dependence/addiction is mediated by complex neural mechanisms that involve multiple brain circuits and neuroadaptive changes in a variety of neurotransmitter and neuropeptide systems. Although recent studies have provided substantial information on the neurobiological mechanisms that drive alcohol drinking behavior, significant challenges remain in understanding how alcohol-induced neuroadaptations occur and how different neurocircuits and pathways cross-talk. This review article highlights recent progress in understanding neural mechanisms of alcohol addiction from the perspectives of the development and maintenance of alcohol dependence. It provides insights on cross talks of different mechanisms and reviews the latest studies on metaplasticity, structural plasticity, interface of reward and stress pathways, and cross-talk of different neural signaling systems involved in binge-like drinking and alcohol dependence. Published by Elsevier Ltd.
C1 [Cui, Changhai; Noronha, Antonio] NIAAA, Div Neurosci & Behav, NIH, Bethesda, MD 20892 USA.
[Morikawa, Hitoshi] Univ Texas Austin, Waggoner Ctr Alcohol & Addict Res, Austin, TX 78712 USA.
[Alvarez, Veronica A.; Wilcox, Mark V.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
[Stuber, Garret D.] Univ N Carolina, UNC Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA.
[Stuber, Garret D.] Univ N Carolina, UNC Sch Med, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA.
[Szumlinski, Karen K.] Univ Calif Santa Barbara, Dept Psychol & Brain Sci, Santa Barbara, CA 93106 USA.
[Kash, Thomas L.] Univ N Carolina, UNC Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Roberto, Marisa] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA.
RP Cui, CH (reprint author), NIAAA, Div Neurosci & Behav, 5635 Fishers Lane, Bethesda, MD 20892 USA.
EM changhai.cui@nih.gov; anoronha@willco.niaaa.nih.gov
RI Kash, Thomas/G-9625-2013; Alvarez, Veronica /E-9745-2015; Stuber,
Garret/E-1160-2011
OI Alvarez, Veronica /0000-0003-2611-8675;
FU NIH [R01AA015521, DA015687]; NIAAA [ZIA-AA000421]; ABMRF;
[R01DA032750]; [R21DA029325]; [R01AA016650]; [R01DA024038];
[U01AA020911]; [R00AA017668]; [R01AA17447]; [R01AA015566];
[P60AA06420]; [R01AA016985]
FX The work was supported by NIH grants R01AA015521 and DA015687 to HM,
NIAAA intramural program ZIA-AA000421 to VAA, R01DA032750, R21DA029325,
and ABMRF grant to GDS, R01AA016650 and R01DA024038 to KKS, U01AA020911
and R00AA017668 to TLK, R01AA17447, R01AA015566, P60AA06420, and
R01AA016985 to MR.
NR 144
TC 27
Z9 29
U1 2
U2 71
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 APR
PY 2013
VL 67
BP 223
EP 232
DI 10.1016/j.neuropharm.2012.09.022
PG 10
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 097ME
UT WOS:000315477400025
PM 23159531
ER
PT J
AU Herman, MA
Kallupi, M
Luu, G
Oleata, CS
Heilig, M
Koob, GF
Ciccocioppo, R
Roberto, M
AF Herman, Melissa A.
Kallupi, Marsida
Luu, George
Oleata, Christopher S.
Heilig, Markus
Koob, George F.
Ciccocioppo, Roberto
Roberto, Marisa
TI Enhanced GABAergic transmission in the central nucleus of the amygdala
of genetically selected Marchigian Sardinian rats: Alcohol and CRF
effects
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Amygdala; GABA; Alcohol; CRF; CRF1 antagonist; Electrophysiology
ID CORTICOTROPIN-RELEASING-FACTOR; AMINOBUTYRIC-ACID RELEASE;
ETHANOL-DEPENDENT RATS; SYNAPTIC GABA(A) RECEPTORS; CROSS-FOSTERING
ANALYSIS; PREFERRING MSP RATS; PROTEIN-KINASE; SPONTANEOUS
NEUROTRANSMISSION; CONDITIONED FEAR; CENTRAL SYNAPSES
AB The GABAergic system in the central amygdala (CeA) plays a major role in ethanol dependence and the anxiogenic-like response to ethanol withdrawal. Alcohol dependence is associated with increased corticotropin releasing factor (CRF) influence on CeA GABA release and CRF type 1 receptor (CRF1) antagonists prevent the excessive alcohol consumption associated with dependence. Genetically selected Marchigian Sardinian (msP) rats have an overactive extrahypothalamic CRF1 system, are highly sensitive to stress, and display an innate preference for alcohol. The present study examined differences in CeA GABAergic transmission and the effects of ethanol, CRF and a CRF1 antagonist in msP, Sprague Dawley, and Wistar rats using an electrophysiological approach. We found no significant differences in membrane properties or mean amplitude of evoked GABA(A)-inhibitory postsynaptic potentials (IPSPs). However, paired-pulse facilitation (PPF) ratios of evoked IPSPs were significantly lower and spontaneous miniature inhibitory postsynaptic current (mIPSC) frequencies were higher in msP rats, suggesting increased CeA GABA release in msP as compared to Sprague Dawley and Wistar rats. The sensitivity of spontaneous GABAergic transmission to ethanol (44 mM), CRF (200 nM) and CRF1 antagonist (R121919, 1 mu M) was comparable in msP, Sprague Dawley, and Wistar rats. However, a history of ethanol drinking significantly increased the baseline mIPSC frequency and decreased the effects of a CRF1 antagonist in msP rats, suggesting increased GABA release and decreased CRF1 sensitivity. These results provide electrophysiological evidence that msP rats display distinct CeA GABAergic activity as compared to Sprague Dawley and Wistar rats. The elevated GABAergic transmission observed in naive msP rats is consistent with the neuroadaptations reported in Sprague Dawley rats after the development of ethanol dependence. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Herman, Melissa A.; Kallupi, Marsida; Luu, George; Oleata, Christopher S.; Koob, George F.; Roberto, Marisa] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA.
[Kallupi, Marsida; Ciccocioppo, Roberto] Univ Camerino, Sch Pharm, Pharmacol Unit, I-62032 Camerino, Italy.
[Heilig, Markus] NIAAA, Lab Clin & Translat Sci, NIH, Bethesda, MD 20892 USA.
RP Roberto, M (reprint author), Scripps Res Inst, Comm Neurobiol Addict Disorders, SP30-1150,10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM mroberto@scripps.edu
RI koob, george/P-8791-2016;
OI Heilig, Markus/0000-0003-2706-2482; Kallupi, Marsida/0000-0002-8688-709X
FU NIH [AA017447, AA015566, AA006420, AA016985, F32AA020430, AA008459]
FX This is manuscript number 21980 from The Scripps Research Institute. We
thank Jenica Tapocik and Sun Hui at The National Institute on Alcohol
Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, for
their technical assistance with genotyping. Supported by grants from
NIH: AA017447, AA015566, AA006420, AA016985, F32AA020430 and AA008459.
The compound R121919 was synthesized and generously contributed by Dr.
Kenner Rice at the Drug Design and Synthesis Section, Chemical Biology
Research Branch, National Institute on Drug Abuse, National Institutes
of Health, Bethesda, MD.
NR 69
TC 14
Z9 15
U1 2
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 APR
PY 2013
VL 67
BP 337
EP 348
DI 10.1016/j.neuropharm.2012.11.026
PG 12
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 097ME
UT WOS:000315477400038
PM 23220399
ER
PT J
AU Orru, M
Guitart, X
Karcz-Kubicha, M
Solinas, M
Justinova, Z
Barodia, SK
Zanoveli, J
Cortes, A
Lluis, C
Casado, V
Moeller, FG
Ferre, S
AF Orru, Marco
Guitart, Xavier
Karcz-Kubicha, Marzena
Solinas, Marcello
Justinova, Zuzana
Barodia, Sandeep Kumar
Zanoveli, Janaina
Cortes, Antoni
Lluis, Carme
Casado, Vicent
Moeller, F. Gerard
Ferre, Sergi
TI Psychostimulant pharmacological profile of paraxanthine, the main
metabolite of caffeine in humans
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Caffeine; Paraxanthine; Psychostimulant; Dopamine release;
Phosphodiesterase inhibitor; Rat striatum; Drug discrimination
ID ADENOSINE RECEPTOR ANTAGONISTS; NITRIC-OXIDE SYNTHASE; CYCLIC-NUCLEOTIDE
PHOSPHODIESTERASES; A(2A) RECEPTORS; NUCLEUS-ACCUMBENS; LOCOMOTOR
BEHAVIOR; DOPAMINE RELEASE; PLACE PREFERENCE; CELL-MEMBRANE; RAT
STRIATUM
AB Caffeine induces locomotor activation by its ability to block adenosine receptors. Caffeine is metabolized to several methylxanthines, with paraxanthine being the main metabolite in humans. In this study we show that in rats paraxanthine has a stronger locomotor activating effect than caffeine or the two other main metabolites of caffeine, theophylline and theobromine. As previously described for caffeine, the locomotor activating doses of paraxanthine more efficiently counteract the locomotor depressant effects of an adenosine A(1) than an adenosine A(2A) receptor agonist. In drug discrimination experiments in rats trained to discriminate a maximal locomotor activating dose of caffeine, paraxanthine, unlike theophylline, generalized poorly to caffeine suggesting the existence of additional mechanisms other than adenosine antagonism in the behavioral effects of paraxanthine. Pretreatment with the nitric oxide inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) reduced the locomotor activating effects of paraxanthine, but not caffeine. On the other hand, pretreatment with the selective cGMP-preferring phosphodiesterase PDE9 inhibitor BAY 73-6691, increased locomotor activity induced by caffeine, but not paraxanthine. Ex vivo experiments demonstrated that paraxanthine, but not caffeine, can induce cGMP accumulation in the rat striatum. Finally, in vivo microdialysis experiments showed that paraxanthine, but not caffeine, significantly increases extracellular levels of dopamine in the dorsolateral striatum, which was blocked by L-NAME. These findings indicate that inhibition of cGMP-preferring PDE is involved in the locomotor activating effects of the acute administration of paraxanthine. The present results demonstrate a unique psychostimulant profile of paraxanthine, which might contribute to the reinforcing effects of caffeine in humans. Published by Elsevier Ltd.
C1 [Orru, Marco; Guitart, Xavier; Karcz-Kubicha, Marzena; Solinas, Marcello; Justinova, Zuzana; Barodia, Sandeep Kumar; Zanoveli, Janaina; Ferre, Sergi] NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Solinas, Marcello] INSERM, U1084, Expt & Clin Neurosci Lab, Neurobiol & Neuropharmacol Addict Grp, Poitiers, France.
[Cortes, Antoni; Lluis, Carme; Casado, Vicent] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, Barcelona, Spain.
[Zanoveli, Janaina] Univ Fed Parana, Dept Pharmacol, BR-80060000 Curitiba, Parana, Brazil.
[Moeller, F. Gerard] Univ Texas Hlth Sci Ctr Houston, Dept Psychiat & Behav Sci, Ctr Neurobehav Res Addict, Houston, TX USA.
RP Ferre, S (reprint author), NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sferre@intra.nida.nih.gov
RI Justinova, Zuzana/A-9109-2011; Ferre, Sergi/K-6115-2014; Solinas,
Marcello/M-3500-2016; Casado, Vicent/K-1660-2014;
OI Justinova, Zuzana/0000-0001-5793-7484; Ferre, Sergi/0000-0002-1747-1779;
Solinas, Marcello/0000-0002-0664-5964; Casado,
Vicent/0000-0002-1764-3825
FU NIDA Intramural Research Program
FX Supported by funding from NIDA Intramural Research Program.
NR 59
TC 13
Z9 14
U1 2
U2 55
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 APR
PY 2013
VL 67
BP 476
EP 484
DI 10.1016/j.neuropharm.2012.11.029
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 097ME
UT WOS:000315477400051
PM 23261866
ER
PT J
AU Deo, AJ
Huang, YY
Hodgkinson, CA
Xin, YR
Oquendo, MA
Dwork, AJ
Arango, V
Brent, DA
Goldman, D
Mann, JJ
Haghighi, F
AF Deo, Anthony J.
Huang, Yung-yu
Hodgkinson, Colin A.
Xin, Yurong
Oquendo, Maria A.
Dwork, Andrew J.
Arango, Victoria
Brent, David A.
Goldman, David
Mann, J. John
Haghighi, Fatemeh
TI A large-scale candidate gene analysis of mood disorders: evidence of
neurotrophic tyrosine kinase receptor and opioid receptor signaling
dysfunction
SO PSYCHIATRIC GENETICS
LA English
DT Article
DE linkage and association; mood disorders; neurotrophic tyrosine kinase
receptor; opioid receptor; type 2; kappa 1
ID MAJOR DEPRESSIVE DISORDER; GENOME-WIDE ASSOCIATION; AND/OR LINKAGE
DISEQUILIBRIUM; MESSENGER-RNA EXPRESSION; PROBE LEVEL DATA;
SUICIDAL-BEHAVIOR; BIPOLAR DISORDER; POPULATION STRATIFICATION;
ANTIDEPRESSANT RESPONSE; CLINICAL PREDICTORS
AB Background Despite proven heritability, little is known about the genetic architecture of mood disorders. Although a number of family and case-control studies have examined the genetics of mood disorders, none have carried out joint linkage-association studies and sought to validate the results with gene expression analyses in an independent cohort.
Methods We present findings from a large candidate gene study that combines linkage and association analyses using families and singletons, providing a systematic candidate gene investigation of mood disorder. For this study, 876 individuals were recruited, including 83 families with 313 individuals and 563 singletons. This large-scale candidate gene analysis included 130 candidate genes implicated in addictive and other psychiatric disorders. These data showed significant genetic associations for 28 of these candidate genes, although none remained significant after correction for multiple testing. To evaluate the functional significance of these 28 candidate genes in mood disorders, we examined the transcriptional profiles of these genes within the dorsolateral prefrontal cortex and anterior cingulate for 21 cases with mood disorders and 25 nonpsychiatric controls, and carried out a pathway analysis to identify points of high connectivity suggestive of particular molecular pathways that may be dysregulated.
Results Two primary gene candidates were supported by the linkage-association, gene expression profiling, and network analysis: neurotrophic tyrosine kinase receptor, type 2 (NTRK2), and the opioid receptor, kappa 1 (OPRK1).
Conclusion This study supports a role for NTRK2 and OPRK1 signaling in the pathophysiology of mood disorder. The unique approach incorporating evidence from multiple experimental and computational modalities enhances confidence in these findings. Psychiatr Genet 23:47-55 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. Psychiatric Genetics 2013, 23:47-55
C1 [Deo, Anthony J.; Huang, Yung-yu; Xin, Yurong; Oquendo, Maria A.; Dwork, Andrew J.; Arango, Victoria; Mann, J. John; Haghighi, Fatemeh] Columbia Univ, New York State Psychiat Inst, Dept Psychiat, Div Mol Imaging & Neuropathol, New York, NY 10032 USA.
[Hodgkinson, Colin A.; Goldman, David] NIAAA, Sect Human Neurogenet, Neurogenet Lab, Rockville, MD 20852 USA.
[Brent, David A.] Western Psychiat Inst & Clin, Dept Child & Adolescent Psychiat, Pittsburgh, PA USA.
RP Haghighi, F (reprint author), Columbia Univ, New York State Psychiat Inst, Dept Psychiat, Div Mol Imaging & Neuropathol, 1051 Riverside Dr,Box 42, New York, NY 10032 USA.
EM fgh3@columbia.edu
RI Arango, Victoria/K-9377-2015; Goldman, David/F-9772-2010
OI Arango, Victoria/0000-0001-8811-400X; Goldman, David/0000-0002-1724-5405
FU [MH40210]; [MH62185]; [MH64168]; [K22 HG2915]; [MH074118];
[MH59710]; [MH48514]
FX This work is supported by grants MH40210, MH62185, MH64168, K22 HG2915,
MH074118, MH59710, and MH48514. The analyses were carried out on
computing resources supported by the National Science Foundation under
the following NSF programs: Partnerships for Advanced Computational
Infrastructure, Distributed Terascale Facility (DTF) and Terascale
Extensions: Enhancements to the Extensible Terascale Facility.
NR 76
TC 10
Z9 10
U1 0
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0955-8829
EI 1473-5873
J9 PSYCHIAT GENET
JI Psychiatr. Genet.
PD APR
PY 2013
VL 23
IS 2
BP 47
EP 55
DI 10.1097/YPG.0b013e32835d7028
PG 9
WC Genetics & Heredity; Neurosciences
SC Genetics & Heredity; Neurosciences & Neurology
GA 098CK
UT WOS:000315522800001
PM 23277131
ER
PT J
AU Laditka, SB
Laditka, JN
Liu, R
Price, AE
Friedman, DB
Wu, B
Bryant, LL
Corwin, SJ
Ivey, SL
AF Laditka, Sarah B.
Laditka, James N.
Liu, Rui
Price, Anna E.
Friedman, Daniela B.
Wu, Bei
Bryant, Lucinda L.
Corwin, Sara J.
Ivey, Susan L.
TI How do older people describe others with cognitive impairment? A
multiethnic study in the United States
SO AGEING & SOCIETY
LA English
DT Article
DE Alzheimer's disease; brain health; cognition; dementia; focus groups;
memory; qualitative research; senility
ID ALZHEIMER-DISEASE; PHYSICAL-ACTIVITY; HEALTHY BRAIN; DEMENTIA;
AMERICANS; BELIEFS; ADULTS; PERCEPTIONS; POPULATION; PREVALENCE
AB We studied how older people describe others with cognitive impairment. Forty-two focus groups represented African Americans, American Indians, Chinese Americans, Latinos, Vietnamese Americans, and Whites other than Latinos (Whites) (N=396, ages 50+), in nine locations in the United States of America. Axial coding connected categories and identified themes. The constant comparison method compared themes across ethnic groups. African Americans, American Indians and Whites emphasised memory loss. African Americans, American Indians, Latinos and Whites stressed withdrawal, isolation and repetitive speech. African Americans, American Indians, Vietnamese Americans and Whites emphasised 'slow thinking'. Only Whites described mood swings and personality changes. Many participants attributed dementia to stress. Terms describing others with dementia included 'Alzheimer's', 'dementia', 'senile' and 'crazy'. Euphemisms were common ('senior moment', 'old timer's disease'). Responses focused on memory, with limited mention of other cognitive functions. Differences among ethnic groups in descriptions of cognitive health and cognitive impairment underscore the need to tailor public health messages about cognitive health to ways that people construe its loss, and to their interest in maintaining it, so that messages and terms used are familiar, understandable and relevant to the groups for which they are designed. Health promotion efforts should develop ethnically sensitive ways to address the widely held misperception that even serious cognitive impairment is a normal characteristic of ageing and also to address stigma associated with cognitive impairment.
C1 [Laditka, Sarah B.; Laditka, James N.] Univ N Carolina, Dept Publ Hlth Sci, Charlotte, NC 28223 USA.
[Liu, Rui] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
[Price, Anna E.] Sacred Heart Univ, Dept Phys Therapy & Human Movement Sci, Fairfield, CT USA.
[Friedman, Daniela B.; Corwin, Sara J.] Univ S Carolina, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA.
[Wu, Bei] Duke Univ, Sch Nursing, Durham, NC USA.
[Bryant, Lucinda L.] Univ Colorado Denver, Colorado Sch Publ Hlth, Dept Community & Behav Hlth, Aurora, CO USA.
[Ivey, Susan L.] Univ Calif Berkeley, Sch Publ Hlth, Div Community Hlth & Human Dev, Berkeley, CA 94720 USA.
RP Laditka, SB (reprint author), Univ N Carolina, Dept Publ Hlth Sci, 9201 Univ City Blvd, Charlotte, NC 28223 USA.
EM sladitka@uncc.edu
NR 48
TC 7
Z9 7
U1 3
U2 36
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0144-686X
EI 1469-1779
J9 AGEING SOC
JI Ageing Soc.
PD APR
PY 2013
VL 33
BP 369
EP 392
DI 10.1017/S0144686X11001255
PN 3
PG 24
WC Gerontology
SC Geriatrics & Gerontology
GA 091XP
UT WOS:000315083400001
ER
PT J
AU Ghirlando, R
Felsenfeld, G
AF Ghirlando, Rodolfo
Felsenfeld, Gary
TI Chromatin structure outside and inside the nucleus
SO BIOPOLYMERS
LA English
DT Review
DE chromatin; nuclear organization; 30 nm fiber
ID HIGHER-ORDER STRUCTURE; NUCLEOSOME CORE PARTICLE; BETA-GLOBIN LOCUS; 30
NM; CRYOELECTRON MICROSCOPY; LINKER HISTONE; HUMAN GENOME; IN-SITU;
FIBER; ORGANIZATION
AB The structure of the 30-nm chromatin fiber has provided, over the years, an important reference in chromatin studies. Originally derived from electron microscopic studies of soluble chromatin fibers released by restriction digestion, the gross structural features of such fragments have been supported by biophysical methods such as low angle X-ray and neutron scattering, sedimentation, light scattering, and electric dichroism. Electron microscopy and sedimentation velocity measurements demonstrated that reconstituted chromatin fibers, prepared from repeating arrays of high affinity nucleosome positioning sequences, retain the same overall features as observed for native chromatin fibers. It had been suggested that the 30 nm fiber might be the form assumed in vivo by transcriptionally silent chromatin, but individual gene or genome-wide studies of chromatin released from nuclei do not reveal any such simple correlation. Furthermore, even though the 30 nm fiber has been thought to represent an intermediate in the hierarchical folding of DNA into chromosomes, most analyses of chromatin folding within the nucleus do not detect any regular extended compact structures. However, there are important exceptions in chicken erythroid cell nuclei as well as in transcribed regions that form extended loops. Localized domains within the nucleus, either at the surface of chromosome domains or constrained as a specialized kind of constitutive heterochromatin by specific DNA binding proteins, may adopt 30 nm fiber-like structures. (c) 2012 Wiley Periodicals, Inc. Biopolymers 99: 225232, 2013.
C1 [Ghirlando, Rodolfo; Felsenfeld, Gary] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Felsenfeld, G (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM gary.felsenfeld@nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, NIH
FX Contract grant sponsor: Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases, NIH
NR 63
TC 10
Z9 10
U1 2
U2 81
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-3525
J9 BIOPOLYMERS
JI Biopolymers
PD APR
PY 2013
VL 99
IS 4
SI SI
BP 225
EP 232
DI 10.1002/bip.22157
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 089RB
UT WOS:000314926600002
PM 23348669
ER
PT J
AU Minton, AP
AF Minton, Allen P.
TI Quantitative assessment of the relative contributions of steric
repulsion and chemical interactions to macromolecular crowding
SO BIOPOLYMERS
LA English
DT Article
DE excluded volume; steric repulsion; weak binding; equivalent hard
particle model
ID PROTEIN-PROTEIN INTERACTIONS; BOVINE SERUM-ALBUMIN; MODEL; VOLUME;
CONSEQUENCES; MIXTURES
AB The term macromolecular crowding denotes the combined effects of high volume fractions of nominally unrelated macromolecules upon the equilibrium and transport properties of all macrosolutes, dilute as well as concentrated, in the crowded medium. We present a formal partitioning of the total crowding effect into contributions from steric exclusion (excluded volume) and weak, nonspecific attractive interactions between a concentrated crowding agent and reactant and product species present at trace concentration. A numerical example of the combined effect of both steric and chemical interactions between crowder and tracer upon the reversible dimerization of tracer is presented, based upon reasonable estimates of the magnitude of both repulsive and attractive interactions between tracer and crowder species. (c) 2012Wiley Periodicals, Inc. Biopolymers 99: 239244, 2013.
C1 NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA.
RP Minton, AP (reprint author), NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA.
EM minton@helix.nih.gov
OI Minton, Allen/0000-0001-8459-1247
FU National Institute of Diabetes and Digestive and Kidney Diseases, NIH
FX Contract grant sponsor: Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases, NIH
NR 23
TC 50
Z9 50
U1 1
U2 64
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-3525
J9 BIOPOLYMERS
JI Biopolymers
PD APR
PY 2013
VL 99
IS 4
SI SI
BP 239
EP 244
DI 10.1002/bip.22163
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 089RB
UT WOS:000314926600004
PM 23348671
ER
PT J
AU Thanos, PK
Robison, LS
Robinson, JK
Michaelides, M
Wang, GJ
Volkow, ND
AF Thanos, Panayotis K.
Robison, Lisa S.
Robinson, John K.
Michaelides, Michael
Wang, Gene-Jack
Volkow, Nora D.
TI Obese rats with deficient leptin signaling exhibit heightened
sensitivity to olfactory food cues
SO SYNAPSE
LA English
DT Article
DE novelty-seeking; food restriction; olfactory stimulus; leptin; obesity
ID BINGE-EATING DISORDER; RECEPTOR MESSENGER-RNA; LONG-TERM POTENTIATION;
DOPAMINE D2 RECEPTOR; ZUCKER RATS; NOVELTY-SEEKING;
INDIVIDUAL-DIFFERENCES; ENERGY-BALANCE; ANXIETY-LIKE; WEIGHT-LOSS
AB The Zucker rat is used as a model of genetic obesity, and while Zucker rats have been well studied for their reduced sensitivity to leptin signaling and subsequent weight gain, little work has examined their responses to environmental signals that are associated with hedonic feeding. This study evaluated the effects of a high-fat food olfactory cue (bacon) in stimulating nose-poke food-seeking behavior on first exposure (novel) and after a period of access for consumption (familiar) in lean and obese Zucker rats at either 4 or 12 months of age, and under ad-lib fed (unrestricted; U) or chronically food-restricted (70% of ad-lib; R) conditions. Baseline nose-poke levels were comparable amongst all groups. At 4 months of age, only ObU rats displayed increased behavioral activation to familiar food cues. Twelve-month-old Ob rats, regardless of diet, exhibited substantially greater food-seeking behavior when exposed to both the novel and familiar olfactory cues. A strong positive correlation between body weight and nose-poke entries for the familiar food cue was observed at both ages, while this correlation for the novel food cue was significant in 12month-old rats only. Similarly, there were strong positive correlations between food intake and poke entries for the familiar food cue was observed at both ages, while this correlation for the novel food cue was significant in 12month-old rats only. Although it is possible that differences in olfactory sensitivity contribute to these behavioral effects, our findings support the interactions between food intake, obesity, and food-seeking behavior and are consistent with leptin inhibiting the brain's reactivity to food cues and suggest that the enhanced sensitivity to the food cues with leptin deficiency is likely to contribute to overeating and weight gain. Synapse, 2013. (c) 2012 Wiley Periodicals, Inc.
C1 [Thanos, Panayotis K.; Robison, Lisa S.; Volkow, Nora D.] NIAAA, Lab Neuroimaging, NIH, Bethesda, MD 20892 USA.
[Thanos, Panayotis K.; Robison, Lisa S.; Michaelides, Michael; Wang, Gene-Jack] Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA.
[Thanos, Panayotis K.; Robison, Lisa S.; Robinson, John K.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11790 USA.
RP Thanos, PK (reprint author), NIAAA, Lab Neuroimaging, NIH, Bethesda, MD 20892 USA.
EM thanos@bnl.gov
RI Michaelides, Michael/K-4736-2013
OI Michaelides, Michael/0000-0003-0398-4917
FU NIAAA [AA11034, AA07574, AA07611]; SULI program; IRTA program
FX Contract grant sponsor: NIAAA; Contract grant numbers: AA11034, AA07574,
AA07611; Contract grant sponsors: SULI and IRTA programs
NR 58
TC 11
Z9 11
U1 0
U2 40
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD APR
PY 2013
VL 67
IS 4
BP 171
EP 178
DI 10.1002/syn.21627
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 093BU
UT WOS:000315167500002
PM 23172699
ER
PT J
AU Terracciano, A
Iacono, D
O'Brien, RJ
Troncoso, JC
An, Y
Sutin, AR
Ferrucci, L
Zonderman, AB
Resnick, SM
AF Terracciano, Antonio
Iacono, Diego
O'Brien, Richard J.
Troncoso, Juan C.
An, Yang
Sutin, Angelina R.
Ferrucci, Luigi
Zonderman, Alan B.
Resnick, Susan M.
TI Personality and resilience to Alzheimer's disease neuropathology: a
prospective autopsy study
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Alzheimer's disease; Dementia; Asymptomatic; Personality; Neuroticism;
Depression; Conscientiousness; Prospective cohort study; Autopsy;
Neurofibrillary tangles; A beta neuritic plaques; Neuropathology
ID DEPRESSIVE SYMPTOMS; 5-FACTOR MODEL; NEUROFIBRILLARY TANGLES;
PSYCHOLOGICAL DISTRESS; COGNITIVE IMPAIRMENT; DEMENTIA; RISK; OLDER;
LIFE; AGE
AB Alzheimer's disease (AD) neuropathology is found at autopsy in approximately 30% of cognitively normal older individuals. We examined whether personality traits are associated with such resilience to clinical dementia in individuals with AD neuropathology. Broad factors and specific facets of personality were assessed up to 28 years (mean 11 +/- 7 years) before onset of dementia and up to 30 years (mean 15 +/- 7 years) before death in a cohort (n = 111) evaluated for AD neuropathology at autopsy. Individuals with higher baseline scores on vulnerability to stress, anxiety, and depression (neuroticism: odds ratio, 2.0; 95% confidence interval, 1.2-3.5), or lower scores on order and competence (conscientiousness: odds ratio, 0.4; 95% confidence interval, 0.2-0.9) were less likely to remain asymptomatic in the presence of AD neuropathology. Neuroticism (r = 0.26), low agreeableness (r = -0.34), and some facets were also significantly associated with advanced stages of neurofibrillary tangles, but the associations between personality traits and risk of clinical dementia were mostly unchanged by controlling for the extent of neurofibrillary tangles and A beta neuritic plaques. In sum, a resilient personality profile is associated with lower risk or delay of clinical dementia even in persons with AD neuropathology. Published by Elsevier Ltd.
C1 [Terracciano, Antonio; An, Yang; Sutin, Angelina R.; Ferrucci, Luigi; Zonderman, Alan B.; Resnick, Susan M.] NIA, NIH, Baltimore, MD 21224 USA.
[Terracciano, Antonio; Sutin, Angelina R.] Florida State Univ, Coll Med, Tallahassee, FL 32306 USA.
[Iacono, Diego] Karolinska Inst, Brain Bank, Dept Neurobiol, Stockholm, Sweden.
[Iacono, Diego; Troncoso, Juan C.] Johns Hopkins Univ, Div Neuropathol, Baltimore, MD USA.
[O'Brien, Richard J.; Troncoso, Juan C.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
RP Terracciano, A (reprint author), NIH Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM TerraccianoA@mail.nih.gov
RI terracciano, antonio/B-1884-2008;
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institutes of Health, National Institute on Aging; Johns
Hopkins University Alzheimer's Disease Research Center [NIA P50AG05146]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Aging, and The
Johns Hopkins University Alzheimer's Disease Research Center (NIA
P50AG05146).
NR 50
TC 17
Z9 17
U1 1
U2 53
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 APR
PY 2013
VL 34
IS 4
BP 1045
EP 1050
DI 10.1016/j.neurobiolaging.2012.08.008
PG 6
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 086ST
UT WOS:000314708000004
PM 23040035
ER
PT J
AU Kumar, A
Gibbs, JR
Beilina, A
Dillman, A
Kumaran, R
Trabzuni, D
Ryten, M
Walker, R
Smith, C
Traynor, BJ
Hardy, J
Singleton, AB
Cookson, MR
AF Kumar, Azad
Gibbs, J. Raphael
Beilina, Alexandra
Dillman, Allissa
Kumaran, Ravindran
Trabzuni, Daniah
Ryten, Mina
Walker, Robert
Smith, Colin
Traynor, Bryan J.
Hardy, John
Singleton, Andrew B.
Cookson, Mark R.
TI Age-associated changes in gene expression in human brain and isolated
neurons
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Aging; Cerebral cortex; Cerebellum; Purkinje cells; Microarrays
ID ALZHEIMERS-DISEASE; MOUSE; CLONING; IDENTIFICATION; TRANSCRIPTOME;
LONGEVITY; BIOLOGY; BLOOD; LISTS
AB Previous studies have suggested that there are genes whose expression levels are associated with chronological age. However, which genes show consistent age association across studies, and which are specific to a given organism or tissue remains unresolved. Here, we reassessed this question using 2 independently ascertained series of human brain samples from 2 anatomic regions, the frontal lobe of the cerebral cortex and cerebellum. Using microarrays to estimate gene expression, we found 60 associations between expression and chronological age that were statistically significant and were replicated in both series in at least 1 tissue. There were a greater number of significant associations in the frontal cortex compared with the cerebellum. We then repeated the analysis in a subset of samples using laser capture microdissection to isolate Purkinje neurons from the cerebellum. We were able to replicate 5 gene associations from either frontal cortex or cerebellum in the Purkinje cell dataset, suggesting that there is a subset of genes which have robust changes with aging. Of these, the most consistent and strongest association was with expression of RHBDL3, a rhomboid protease family member. We confirmed several hits using an independent technique (quantitative reverse transcriptase polymerase chain reaction) and in an independent published sample series that used a different array platform. We also interrogated larger patterns of age-related gene expression using weighted gene correlation network analysis. We found several modules that showed significant associations with chronological age and, of these, several that showed negative associations were enriched for genes encoding components of mitochondria. Overall, our results show that there is a distinct and reproducible gene signature for aging in the human brain. Published by Elsevier Ltd.
C1 [Kumar, Azad; Gibbs, J. Raphael; Beilina, Alexandra; Dillman, Allissa; Kumaran, Ravindran; Traynor, Bryan J.; Singleton, Andrew B.; Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Gibbs, J. Raphael; Trabzuni, Daniah; Ryten, Mina; Hardy, John] UCL Inst Nerurol, Dept Mol Neurosci, London, England.
[Walker, Robert; Smith, Colin] Univ Edinburgh, Dept Neuropathol, Edinburgh, Midlothian, Scotland.
[Dillman, Allissa] Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
[Trabzuni, Daniah] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia.
RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, 35 Convent Dr, Bethesda, MD 20892 USA.
EM cookson@mail.nih.gov
RI Hardy, John/C-2451-2009; Traynor, Bryan/G-5690-2010; Singleton,
Andrew/C-3010-2009; Trabzuni, Daniah/C-4034-2012
OI Walker, Robert/0000-0001-7383-7846; Trabzuni, Daniah/0000-0003-4826-9570
FU NIH, National Institute on Aging [ZO1-AG000947, Z01-AG000185]; UK
Medical Research Council [G0802462]; Medical Research Council
[G0901254]; King Faisal Specialist Hospital and Research Centre, Saudi
Arabia
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging (ZO1-AG000947 and Z01-AG000185)
and by the UK Medical Research Council Biomedical Informatics
Postdoctoral Training Fellowship (G0802462 to MR) and Medical Research
Council Project Grant (grant G0901254 to JH). D. T. was supported by the
King Faisal Specialist Hospital and Research Centre, Saudi Arabia. The
authors thank the LCM core facility at the National Cancer Institute for
help with microdissection.
NR 36
TC 15
Z9 15
U1 2
U2 33
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 APR
PY 2013
VL 34
IS 4
BP 1199
EP 1209
DI 10.1016/j.neurobiolaging.2012.10.021
PG 11
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 086ST
UT WOS:000314708000021
PM 23177596
ER
PT J
AU Schupf, N
Barral, S
Perls, T
Newman, A
Christensen, K
Thyagarajan, B
Province, M
Rossi, WK
Mayeux, R
AF Schupf, Nicole
Barral, Sandra
Perls, Thomas
Newman, Anne
Christensen, Kaare
Thyagarajan, Bharat
Province, Michael
Rossi, Winifred K.
Mayeux, Richard
TI Apolipoprotein E and familial longevity
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Exceptional longevity; Familial longevity; Offspring; APOE; TOMM40
ID GENOME-WIDE ASSOCIATION; E POLYMORPHISM; E GENOTYPE; APOE; MORTALITY;
FREQUENCY; SURVIVAL; GENE; AGE; NONAGENARIANS
AB Exceptional longevity is associated with substantial heritability. The epsilon 4 allele in apolipoprotein E and the linked G allele in rs2075650 of TOMM40 have been associated with increased mortality and the epsilon 2 allele with decreased mortality, although inconsistently. Offspring from long-lived families and spouse controls were recruited at 3 sites in the United States and Denmark. We used generalized estimating equations to compare the likelihood of carrying risk alleles in offspring (n = 2307) and spouse controls (n = 764), adjusting for age, sex, level of education, and family membership. The likelihood of carrying an APOE epsilon 4 allele or a G allele in rs2075650 was lower (odds ratio [OR], 0.75; p = 0.005 and OR, 0.70; p = 0.002) and the likelihood of carrying an APOE epsilon 2 allele was higher (OR, 1.5; p = 0.007) among family members in the offspring generation than among their spouse controls. Our findings support the hypothesis that both reduction in the frequency of the epsilon 4 allele and increase in the frequency of the epsilon 2 allele contribute to longevity. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Schupf, Nicole; Barral, Sandra; Mayeux, Richard] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA.
[Perls, Thomas] Boston Univ, Med Ctr, Geriatr Sect, Boston, MA USA.
[Newman, Anne] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Christensen, Kaare] Univ So Denmark, Danish Aging Res Ctr, Odense, Denmark.
[Christensen, Kaare] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark.
[Christensen, Kaare] Odense Univ Hosp, Dept Clin Biochem & Pharmacol, DK-5000 Odense, Denmark.
[Thyagarajan, Bharat] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Province, Michael] Washington Univ, Sch Med, Div Stat Genom, Data Management Coordinating Ctr, St Louis, MO USA.
[Rossi, Winifred K.] NIA, Bethesda, MD 20892 USA.
RP Schupf, N (reprint author), Taub Inst Res Alzheimers Dis & Aging Brain, P&S Box Unit 16,630 W 168th St, New York, NY 10032 USA.
EM ns24@columbia.edu
RI Christensen, Kaare/C-2360-2009; Newman, Anne/C-6408-2013;
OI Christensen, Kaare/0000-0002-5429-5292; Newman,
Anne/0000-0002-0106-1150; Perls, Thomas/0000-0002-2492-4334
FU National Institute on Aging (NIA) [U01-AG023712, U01-AG23744,
U01-AG023746, U01-AG023749, U01-AG023755]; NIH/NIA [P01 AG08761]; VELUX
Foundation
FX The work is supported by the National Institute on Aging (NIA
cooperative agreements U01-AG023712, U01-AG23744, U01-AG023746,
U01-AG023749, and U01-AG023755). The Danish 1905-cohort is funded by
NIH/NIA, P01 AG08761. The Danish Aging Research Center is funded by the
VELUX Foundation.
NR 32
TC 17
Z9 18
U1 0
U2 12
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 APR
PY 2013
VL 34
IS 4
BP 1287
EP 1291
DI 10.1016/j.neurobiolaging.2012.08.019
PG 5
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 086ST
UT WOS:000314708000029
PM 23040522
ER
PT J
AU Yeh, TH
Lai, SC
Weng, YH
Kuo, HC
Wu-Chou, YH
Huang, CL
Chen, RS
Chang, HC
Traynor, B
Lu, CS
AF Yeh, Tu-Hsueh
Lai, Szu-Chia
Weng, Yi-Hsin
Kuo, Hung-Chou
Wu-Chou, Yah-Huei
Huang, Chia-Ling
Chen, Rou-Shayn
Chang, Hsiu-Chen
Traynor, Bryan
Lu, Chin-Song
TI Screening for C9orf72 repeat expansions in parkinsonian syndromes
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE C9orf72; GGGGCC hexanucleotide repeat expansion; Frontotemporal dementia
(FTD); Parkinson's disease with dementia (PDD); Progressive supranuclear
palsy (PSP); Corticobasal syndrome (CBS); Dementia with Lewy bodies
(DLB)
AB Parkinsonism might precede, coincide, or follow the behavioral or language-predominant cognitive impairments characteristic of frontotemporal dementia (FTD). In this study, we analyze the hexanucleotide repeat expansions within C9orf72 gene in various parkinsonian syndromes because it is a recently identified important genetic cause of FTD. The expanded hexanucleotide repeat is only identified in our familial FTD patients but not in patients with predominant parkinsonism. The lack of association between abnormal C9orf72 repeat expansion and parkinsonian syndromes might imply pathogenic mechanisms other than tau or Lewy body pathology. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Yeh, Tu-Hsueh; Lai, Szu-Chia; Weng, Yi-Hsin; Chen, Rou-Shayn; Chang, Hsiu-Chen; Lu, Chin-Song] Linkou Med Ctr, Chang Gung Mem Hosp, Dept Neurol, Sect Movement Disorders, Tao Yuan, Taiwan.
[Yeh, Tu-Hsueh; Lai, Szu-Chia; Weng, Yi-Hsin; Kuo, Hung-Chou; Wu-Chou, Yah-Huei; Chen, Rou-Shayn; Chang, Hsiu-Chen; Lu, Chin-Song] Chang Gung Univ, Tao Yuan, Taiwan.
[Yeh, Tu-Hsueh; Lai, Szu-Chia; Weng, Yi-Hsin; Wu-Chou, Yah-Huei; Chen, Rou-Shayn; Chang, Hsiu-Chen; Lu, Chin-Song] Linkou Med Ctr, Chang Gung Mem Hosp, Neurosci Res Ctr, Tao Yuan, Taiwan.
[Kuo, Hung-Chou] Linkou Med Ctr, Chang Gung Mem Hosp, Dept Neurol, Sect Neuromuscular Disorders, Tao Yuan, Taiwan.
[Wu-Chou, Yah-Huei] Linkou Med Ctr, Chang Gung Mem Hosp, Human Mol Genet Lab, Tao Yuan, Taiwan.
[Huang, Chia-Ling] St Pauls Hosp, Dept Neurol, Tao Yuan, Taiwan.
[Traynor, Bryan] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Lu, CS (reprint author), Chang Gung Mem Hosp, Dept Neurol, Sect Movement Disorders, 5 Fu Shin St, Tao Yuan 33305, Taiwan.
EM c81214@adm.cgmh.org.tw
RI Traynor, Bryan/G-5690-2010
FU National Science Council Taiwan [NSC 100-2321-B-182A-004-]; Chang Gung
Medical Foundation Taiwan [BMRPG390041]; Chang Gung University
[EMRPD1B0311]; Intramural Research Program of the NIH, National
Institute on Aging [Z01-AG000949-02]
FX We thank all the participants for their contributions. This work was
supported by the National Science Council Taiwan (grant number: NSC
100-2321-B-182A-004- to T-H Yeh), the Chang Gung Medical Foundation
Taiwan (grant number: BMRPG390041 to C-S Lu), and the Chang Gung
University (grant number: EMRPD1B0311 to C-S Lu). This work was also
supported in part by the Intramural Research Program of the NIH,
National Institute on Aging (Z01-AG000949-02). We are grateful to the
DNA Sequencing Core Laboratory and Genomic Medicine Research Core
Laboratory, Chang Gung Memorial Hospital, Linkou, for technical
assistance.
NR 0
TC 2
Z9 2
U1 0
U2 7
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 APR
PY 2013
VL 34
IS 4
AR 1311. e3
DI 10.1016/j.neurobiolaging.2012.09.002
PG 2
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 086ST
UT WOS:000314708000038
PM 23063644
ER
PT J
AU Jao, T
Vertes, PE
Alexander-Bloch, AF
Tang, IN
Yu, YC
Chen, JH
Bullmore, ET
AF Jao, Tun
Vertes, Petra E.
Alexander-Bloch, Aaron F.
Tang, I-Ning
Yu, Ya-Chih
Chen, Jyh-Horng
Bullmore, Edward T.
TI Volitional eyes opening perturbs brain dynamics and functional
connectivity regardless of light input
SO NEUROIMAGE
LA English
DT Article
DE Eyes open/ eyes closed; Visual input; Resting state; Brain dynamics;
Brain network
ID RESTING-STATE FMRI; LOW-FREQUENCY FLUCTUATION; DEFAULT MODE NETWORK;
SMALL-WORLD NETWORKS; HUMAN VISUAL-CORTEX; ECHO-PLANAR MRI;
CEREBRAL-CORTEX; MOTOR CORTEX; ALPHA-RHYTHM; POSTERIOR CINGULATE
AB The act of opening (or closing) one's eyes has long been demonstrated to impact on brain function. However, the eyes open condition is usually accompanied by visual input, and this effect may have been a significant confounding factor in previous studies. To clarify this situation, we extended the traditional eyes open/closed study to a two-factor balanced, repeated measures resting state fMRI (rs-fMRI) experiment, in which light on/off was also included as a factor. In 16 healthy participants, we estimated the univariate properties of the BOLD signal, as well as a bivariate measure of functional connectivity and multivariate network topology measures. Across all these measures, we demonstrate that human brain adopts a distinctive configuration when eyes are open (compared to when eyes are closed) independently of exogenous light input: (i) the eyes open states were associated with decreased BOLD signal variance (P-value = 0.0004), decreased fractional amplitude of low frequency fluctuation (fALFF. P-value = 0.0061), and decreased Hurst exponent (H. P-value = 0.0321) mainly in the primary and secondary sensory cortical areas, the insula, and the thalamus. (ii) The strength of functional connectivity (FC) between the posterior cingulate cortex (PCC), a major component of the default mode network (DMN), and the bilateral perisylvian and perirolandic regions was also significantly decreased during eyes open states. (iii) On the other hand, the average network connection distance increased during eyes open states (P-value = 0.0139). Additionally, the metrics of univariate, bivariate, and multivariate analyses in this study are significantly correlated. In short, we have shown that the marked effects on the dynamics and connectivity of fMRI time series brought by volitional eyes open or closed are simply endogenous and irrespective of exogenous visual stimulus. The state of eyes open (or closed) may thus be an important factor to control in design of rs-fMRI and even other cognitive block or event-related experiments. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Jao, Tun; Vertes, Petra E.; Alexander-Bloch, Aaron F.; Bullmore, Edward T.] Univ Cambridge, Brain Mapping Unit, Cambridge, England.
[Jao, Tun; Vertes, Petra E.; Alexander-Bloch, Aaron F.; Bullmore, Edward T.] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge, England.
[Vertes, Petra E.] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
[Alexander-Bloch, Aaron F.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
[Alexander-Bloch, Aaron F.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Tang, I-Ning; Yu, Ya-Chih; Chen, Jyh-Horng] Natl Taiwan Univ, Dept Elect Engn, Interdisciplinary MRI MRS Lab, Taipei 106, Taiwan.
[Bullmore, Edward T.] Addenbrookes Hosp, GlaxoSmithKline, Clin Unit Cambridge, Cambridge, England.
[Bullmore, Edward T.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England.
RP Chen, JH (reprint author), Natl Taiwan Univ, Room 706,Ming Da Bldg,Sec 4,1 Roosevelt Rd, Taipei 106, Taiwan.
EM jhchen@ntu.edu.tw; etb23@cam.ac.uk
RI Bullmore, Edward/C-1706-2012;
OI Bullmore, Edward/0000-0002-8955-8283; Alexander-Bloch,
Aaron/0000-0001-6554-1893; Jao, Tun/0000-0002-9379-2398; Vertes, Petra
E./0000-0002-0992-3210
FU National Science Council, Taiwan [NSC 99-2321-B-002-007]; Medical
Research Council; Wellcome Trust; Ministry of Education, Taiwan
FX This research was funded by the National Science Council (NSC
99-2321-B-002-007), Taiwan. The Behavioural and Clinical Neuroscience
Institute is supported by the Medical Research Council and the Wellcome
Trust. Tun Jao is supported by the Ministry of Education, Taiwan. EB is
employed half-time by the University of Cambridge and half-time by
GlaxoSmithKline, plc. We would like to thank Dr. Changwei W. Wu and
Yun-An Huang of National Taiwan University for their helpful discussions
on experimental design.
NR 110
TC 31
Z9 31
U1 3
U2 31
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD APR 1
PY 2013
VL 69
BP 21
EP 34
DI 10.1016/j.neuroimage.2012.12.007
PG 14
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 085PX
UT WOS:000314627800003
PM 23266698
ER
PT J
AU Goh, JO
Beason-Held, LL
An, Y
Kraut, MA
Resnick, SM
AF Goh, Joshua O.
Beason-Held, Lori L.
An, Yang
Kraut, Michael A.
Resnick, Susan M.
TI Frontal function and executive processing in older adults: Process and
region specific age-related longitudinal functional changes
SO NEUROIMAGE
LA English
DT Article
DE Aging; Longitudinal; Cross-sectional; Brain function; Executive
processing
ID ALZHEIMERS-DISEASE; AGING BRAIN; MEMORY; INTERFERENCE; ACTIVATION;
COMPENSATE; DECLINE; SPAN; FMRI
AB Longitudinal studies on aging brain function have shown declines in frontal activity as opposed to the over-recruitment shown in cross-sectional studies. Such mixed findings suggest that age-related changes in frontal activity may be process- and region-specific, having varied associations across different frontal regions involved in distinct cognitive processes, rather than generalized across the frontal cortex. Using data from the Baltimore Longitudinal Study of Aging (BLSA), we examined individual differences through cross-sectional associations at baseline evaluation and longitudinal changes in regional cerebral blood flow (rCBF) in relation to different executive abilities in cognitively normal older adults. We found that, at baseline, greater rCBF in middle frontal regions correlated with better performance in abstraction and chunking, but greater rCBF in the insula and a distinct middle frontal region correlated with poorer inhibition and discrimination, respectively. In addition, increases in frontal rCBF over time were associated with longitudinal declines in abstraction, chunking, inhibition, discrimination, switching, and manipulation. These findings indicate process- and region-specific, rather than uniform, age-related changes in frontal brain-behavior associations, and also suggest that longitudinally high-levels of frontal engagement reflect declining rather than stable cognition. Published by Elsevier Inc.
C1 [Goh, Joshua O.; Beason-Held, Lori L.; An, Yang; Resnick, Susan M.] NIA, Lab Behav Neurosci, Intramural Res Program, Baltimore, MD 21224 USA.
[Kraut, Michael A.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA.
RP Goh, JO (reprint author), 251 Bayview Blvd,Suite 100,Rm 4B316, Baltimore, MD 21224 USA.
EM joshua.goh@nih.gov
RI GOH, JOSHUA/C-8063-2016
OI GOH, JOSHUA/0000-0001-7808-5452
FU Intramural Research Program of the National Institute on Aging; National
Institutes of Health, USA; Research and Development Contract
[N01-AG-3-2124]
FX This work was supported in part by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health, USA, and
by Research and Development Contract N01-AG-3-2124.
NR 37
TC 11
Z9 11
U1 1
U2 33
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 APR 1
PY 2013
VL 69
BP 43
EP 50
DI 10.1016/j.neuroimage.2012.12.026
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 085PX
UT WOS:000314627800005
PM 23266746
ER
PT J
AU Zhang, XC
Lee, MR
Salmeron, BJ
Stein, DJ
Hong, LE
Geng, XJ
Ross, TJ
Li, N
Hodgkinson, C
Shen, PH
Yang, YH
Goldman, D
Stein, EA
AF Zhang, Xiaochu
Lee, Mary R.
Salmeron, Betty Jo
Stein, Dan J.
Hong, L. Elliot
Geng, Xiujuan
Ross, Thomas J.
Li, Nan
Hodgkinson, Colin
Shen, Pei-Hong
Yang, Yihong
Goldman, David
Stein, Elliot A.
TI Prefrontal white matter impairment in substance users depends upon the
catechol-o-methyl transferase (COMT) val158met polymorphism
SO NEUROIMAGE
LA English
DT Article
DE Imaging; Genetics; Nicotine; Addiction; COMT; DTI
ID DIFFUSION TENSOR TRACTOGRAPHY; IOWA GAMBLING TASK; NICOTINE DEPENDENCE;
HUMAN BRAIN; METHAMPHETAMINE ABUSERS; SPATIAL STATISTICS; SMOKING
INITIATION; COCAINE DEPENDENCE; DOPAMINE RELEASE; METHYLTRANSFERASE
AB Individuals addicted to most chemical substances present with hypoactive dopaminergic systems as well as altered prefrontal white matter structure. Prefrontal dopaminergic tone is under genetic control and is influenced by and modulates descending cortico-striatal glutamatergic pathways that in turn, regulate striatal dopamine release. The catechol-O-methyltransferase (COMT) gene contains an evolutionarily recent and common functional variant at codon 108/158 (rs4680) that plays an important role in modulating prefrontal dopaminergic tone. To determine if the COMT val158met genotype influences white matter integrity (i.e., fractional anisotropy (FA)) in substance users, 126 healthy controls and 146 substance users underwent genotyping and magnetic resonance imaging. A general linear model with two between-subjects factors (COMT genotype and addiction status) was performed using whole brain diffusion tensor imaging (DTI) to assess FA A significant Genotype x Drug Use status interaction was found in the left prefrontal cortex. Post-hoc analysis showed reduced prefrontal FA only in Met/Met homozygotes who were also drug users. These data suggest that Met/Met homozygous individuals, in the context of addiction, have increased susceptibility to white matter structural alterations, which might contribute to previously identified structural and functional prefrontal cortical deficits in addiction. Published by Elsevier Inc.
C1 [Zhang, Xiaochu; Lee, Mary R.; Salmeron, Betty Jo; Geng, Xiujuan; Ross, Thomas J.; Yang, Yihong; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA.
[Stein, Dan J.] Univ Cape Town, Dept Psychiat & Mental Hlth, ZA-7925 Cape Town, South Africa.
[Hong, L. Elliot] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA.
[Hodgkinson, Colin; Shen, Pei-Hong; Goldman, David] NIAAA, Neurogenet Lab, DICBR, NIH, Rockville, MD 20852 USA.
[Zhang, Xiaochu; Li, Nan] Chinese Acad Sci, Key Lab Brain Funct & Dis, Hefei 230027, Peoples R China.
[Zhang, Xiaochu; Li, Nan] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Peoples R China.
RP Lee, MR (reprint author), 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM leemary@mail.nih.gov
RI Zhang, Xiaochu/O-9592-2014; Goldman, David/F-9772-2010; Salmeron, Betty
Jo/M-1793-2016; Stein, Dan/A-1752-2008;
OI Zhang, Xiaochu/0000-0002-7541-0130; Goldman, David/0000-0002-1724-5405;
Salmeron, Betty Jo/0000-0003-1699-9333; Stein, Dan/0000-0001-7218-7810;
Ross, Thomas/0000-0002-7745-3572
FU Intramural Research Program of NIDA; Intramural Research Program of
NIAAA; National Natural Science Foundation of China [31171083,
31230032]; Chinese Academy of Sciences the Hundred Talents Program
[BJ2070000047]; Fundamental Research Funds for the Central Universities
of China [WK2070000007]
FX This study was supported by the Intramural Research Programs of NIDA and
NIAAA. XZ is partially supported by the National Natural Science
Foundation of China (31171083, 31230032), the Chinese Academy of
Sciences the Hundred Talents Program (BJ2070000047), and the Fundamental
Research Funds for the Central Universities of China (WK2070000007). We
thank Kimberly Slater, Loretta Spurgeon and Catherine Demers for their
assistance in conducting this study.
NR 61
TC 8
Z9 8
U1 3
U2 24
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 APR 1
PY 2013
VL 69
BP 62
EP 69
DI 10.1016/j.neuroimage.2012.11.056
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 085PX
UT WOS:000314627800007
PM 23219927
ER
PT J
AU Voss, JG
Dobra, A
Morse, C
Kovacs, JA
Danner, RL
Munson, PJ
Logan, C
Rangel, Z
Adelsberger, JW
McLaughlin, M
Adams, LD
Raju, R
Dalakas, MC
AF Voss, Joachim G.
Dobra, Adrian
Morse, Caryn
Kovacs, Joseph A.
Danner, Robert L.
Munson, Peter J.
Logan, Carolea
Rangel, Zoila
Adelsberger, Joseph W.
McLaughlin, Mary
Adams, Larry D.
Raju, Raghavan
Dalakas, Marinos C.
TI Fatigue-Related Gene Networks Identified in CD14(+) Cells Isolated From
HIV-Infected Patients-Part I: Research Findings
SO BIOLOGICAL RESEARCH FOR NURSING
LA English
DT Article
DE CD14; fatigue; cofilin 2; Bayesian inference; prokineticin 2; HIV
ID ACTIVE ANTIRETROVIRAL THERAPY; MITOCHONDRIAL TOXICITY; VIRAL
PERSISTENCE; EXPRESSION; VIRUS; PROTEIN; PATHOGENESIS; MONOCYTES; MEN;
DNA
AB Purpose: Human immunodeficiency virus (HIV)-related fatigue (HRF) is multicausal and potentially related to mitochondrial dysfunction caused by antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs). Methodology: The authors compared gene expression profiles of CD14(+) cells of low versus high fatigued, NRTI-treated HIV patients to healthy controls (n = 5/group). The authors identified 32 genes predictive of low versus high fatigue and 33 genes predictive of healthy versus HIV infection. The authors constructed genetic networks to further elucidate the possible biological pathways in which these genes are involved. Relevance for nursing practice: Genes including the actin cytoskeletal regulatory proteins Prokineticin 2 and Cofilin 2 along with mitochondrial inner membrane proteins are involved in multiple pathways and were predictors of fatigue status. Previously identified inflammatory and signaling genes were predictive of HIV status, clearly confirming our results and suggesting a possible further connection between mitochondrial function and HIV. Isolated CD14(+) cells are easily accessible cells that could be used for further study of the connection between fatigue and mitochondrial function of HIV patients. Implication for Practice: The findings from this pilot study take us one step closer to identifying biomarker targets for fatigue status and mitochondrial dysfunction. Specific biomarkers will be pertinent to the development of methodologies to diagnosis, monitor, and treat fatigue and mitochondrial dysfunction.
C1 [Voss, Joachim G.; Dobra, Adrian; Adams, Larry D.] Univ Washington, Sch Nursing, Biobehav Nursing & Hlth Syst Dept, Seattle, WA 98195 USA.
[Dobra, Adrian] Univ Washington, Dept Stat, Seattle, WA 98195 USA.
[Morse, Caryn; Kovacs, Joseph A.; McLaughlin, Mary] NIAID, Bethesda, MD 20892 USA.
[Morse, Caryn; Kovacs, Joseph A.; Danner, Robert L.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Danner, Robert L.; Logan, Carolea] NIH, Dept Crit Care Med, Ctr Clin, Funct Genom & Prote Facil, Bethesda, MD 20892 USA.
[Munson, Peter J.; Rangel, Zoila] NIH, Ctr Informat Technol, Math & Stat Comp Lab, Bethesda, MD 20892 USA.
[Adelsberger, Joseph W.] NCI, NIH, AIDS Monitoring Lab, Frederick, MD 21701 USA.
[Raju, Raghavan] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA.
[Dalakas, Marinos C.] Univ London Imperial Coll Sci Technol & Med, London, England.
RP Voss, JG (reprint author), Univ Washington, Sch Nursing, Box 357266, Seattle, WA 98195 USA.
EM vossj@uw.edu
FU K-22 National Institute of Nursing Research [NR008672-01]; NIH
[05-ClinicalCenter-0127]
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: Grant support:
K-22 National Institute of Nursing Research NR008672-01, NIH
05-ClinicalCenter-0127.
NR 64
TC 3
Z9 3
U1 1
U2 20
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1099-8004
J9 BIOL RES NURS
JI Biol. Res. Nurs.
PD APR
PY 2013
VL 15
IS 2
BP 137
EP 151
DI 10.1177/1099800411421957
PG 15
WC Nursing
SC Nursing
GA 082BU
UT WOS:000314367500002
PM 23324479
ER
PT J
AU Voss, JG
Dobra, A
Morse, C
Kovacs, JA
Raju, R
Danner, RL
Munson, PJ
Logan, C
Rangel, Z
Adelsberger, JW
McLaughlin, M
Adams, LD
Dalakas, MC
AF Voss, Joachim G.
Dobra, Adrian
Morse, Caryn
Kovacs, Joseph A.
Raju, Raghavan
Danner, Robert L.
Munson, Peter J.
Logan, Carolea
Rangel, Zoila
Adelsberger, Joseph W.
McLaughlin, Mary
Adams, Larry D.
Dalakas, Marinos C.
TI Fatigue-Related Gene Networks Identified in CD14(+) Cells Isolated From
HIV-Infected Patients-Part II: Statistical Analysis
SO BIOLOGICAL RESEARCH FOR NURSING
LA English
DT Article
DE CD14; genetic network; Bayesian inference; liquid association; HIV
ID EXPRESSION DATA; VIRAL PERSISTENCE; CLASSIFICATION; DISCOVERY;
MICROARRAYS; MODELS; ARRAYS; MICE; MEN
AB Purpose: In limited samples of valuable biological tissues, univariate ranking methods of microarray analyses often fail to show significant differences among expression profiles. In order to allow for hypothesis generation, novel statistical modeling systems can be greatly beneficial. The authors applied new statistical approaches to solve the issue of limited experimental data to generate new hypotheses in CD14(+) cells of patients with HIV-related fatigue (HRF) and healthy controls. Methodology: We compared gene expression profiles of CD14(+) cells of nucleoside reverse transcriptase inhibitor (NRTI)-treated HIV patients with low versus high fatigue to healthy controls (n = 5 each). With novel Bayesian modeling procedures, the authors identified 32 genes predictive of low versus high fatigue and 33 genes predictive of healthy versus HIV infection. Sparse association and liquid association networks further elucidated the possible biological pathways in which these genes are involved. Relevance for nursing practice: Genetic networks developed in a comprehensive Bayesian framework from small sample sizes allow nursing researchers to design future research approaches to address such issues as HRF. Implication for practice: The findings from this pilot study may take us one step closer to the development of useful biomarker targets for fatigue status. Specific and reliable tests are needed to diagnosis, monitor and treat fatigue and mitochondrial dysfunction.
C1 [Voss, Joachim G.; Dobra, Adrian; Adams, Larry D.] Univ Washington, Sch Nursing, Biobehav Nursing & Hlth Syst Dept, Seattle, WA 98195 USA.
[Dobra, Adrian] Univ Washington, Dept Stat, Seattle, WA 98195 USA.
[Morse, Caryn; McLaughlin, Mary] NIAID, Bethesda, MD 20892 USA.
[Morse, Caryn; Kovacs, Joseph A.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Raju, Raghavan] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA.
[Danner, Robert L.; Logan, Carolea] NIH, Dept Crit Care Med, Funct Genom & Prote Facil, Ctr Clin, Bethesda, MD 20892 USA.
[Munson, Peter J.; Rangel, Zoila] NIH, Ctr Informat Technol, Math & Stat Comp Lab, Bethesda, MD 20892 USA.
[Adelsberger, Joseph W.] NCI, AIDS Monitoring Lab, NIH, Frederick, MD 21701 USA.
[Dalakas, Marinos C.] Univ London Imperial Coll Sci Technol & Med, London, England.
RP Voss, JG (reprint author), Univ Washington, Sch Nursing, Biobehav Nursing & Hlth Syst Dept, Box 357 266,Room T 624B, Seattle, WA 98195 USA.
EM vossj@u.washington.edu
FU K-22 National Institute of Nursing Research [NR008672-01]; NIH
[05-ClinicalCenter-0127]
FX The authors disclosed receipt of the following financial support for the
research and/or authorship of this article: Grant support: K-22 National
Institute of Nursing Research NR008672-01, NIH 05-ClinicalCenter-0127.
NR 45
TC 1
Z9 1
U1 0
U2 12
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1099-8004
EI 1552-4175
J9 BIOL RES NURS
JI Biol. Res. Nurs.
PD APR
PY 2013
VL 15
IS 2
BP 152
EP 159
DI 10.1177/1099800411423307
PG 8
WC Nursing
SC Nursing
GA 082BU
UT WOS:000314367500003
PM 22084402
ER
PT J
AU Duffy, A
Rahma, O
Greten, TF
AF Duffy, Austin
Rahma, Osama
Greten, Tim F.
TI Prognostic value of cetuximab-related skin toxicity in metastatic
colorectal cancer patients and its correlation with parameters of the
epidermal growth factor receptor signal transduction pathway: Results
from a randomized trial of the GERMAN AIO CRC Study Group
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Letter
C1 [Duffy, Austin; Rahma, Osama; Greten, Tim F.] NCI, GI Malignancies Sect, Bethesda, MD 20892 USA.
RP Duffy, A (reprint author), NCI, GI Malignancies Sect, Bethesda, MD 20892 USA.
EM duffya@mail.nih.gov
RI Greten, Tim/B-3127-2015
OI Greten, Tim/0000-0002-0806-2535
NR 5
TC 3
Z9 3
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD APR 1
PY 2013
VL 132
IS 7
BP 1718
EP 1718
DI 10.1002/ijc.27805
PG 1
WC Oncology
SC Oncology
GA 079NN
UT WOS:000314177500026
PM 22930464
ER
PT J
AU Zhang, SP
Chen, HS
Pfeiffer, RM
AF Zhang, Shunpu
Chen, Huann-Sheng
Pfeiffer, Ruth M.
TI A combined p-value test for multiple hypothesis testing
SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE
LA English
DT Article
DE Bonferoni test; Simes test; Combined p-value test; Family-wise error
rate; Fisher's product test; Rank truncated product (RIP) test;
Truncated product method
ID GENOMEWIDE ASSOCIATION; BONFERRONI PROCEDURE; TRUNCATED PRODUCT
AB Tests that combine p-values, such as Fisher's product test, are popular to test the global null hypothesis H-0 that each of n component null hypotheses, H-1, ... ,H-n, is true versus the alternative that at least one of H-1, ... ,H-n is false, since they are more powerful than classical multiple tests such as the Bonferroni test and the Simes tests. Recent modifications of Fisher's product test, popular in the analysis of large scale genetic studies include the truncated product method (TPM) of Zaykin et al. (2002), the rank truncated product (RTP) test of Dudbridge and Koeleman (2003) and more recently, a permutation based test-the adaptive rank truncated product (ARTP) method of Yu et al. (2009). The TPM and RIP methods require users' specification of a truncation point. The ARTP method improves the performance of the RTP method by optimizing selection of the truncation point over a set of pre-specified candidate points. In this paper we extend the ARTP by proposing to use all the possible truncation points (1, ... ,n} as the candidate truncation points. Furthermore, we derive the theoretical probability distribution of the test statistic under the global null hypothesis H-0. Simulations are conducted to compare the performance of the proposed test with the Bonferroni test, the Simes test, the RTP test, and Fisher's product test. The simulation results show that the proposed test has higher power than the Bonferroni test and the Simes test, as well as the RIP method. It is also significantly more powerful than Fisher's product test when the number of truly false hypotheses is small relative to the total number of hypotheses, and has comparable power to Fisher's product test otherwise. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Zhang, Shunpu] Univ Nebraska, Dept Stat, Lincoln, NE 68583 USA.
[Chen, Huann-Sheng] NCI, Stat Methodol & Applicat Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Zhang, SP (reprint author), Univ Nebraska, Dept Stat, Lincoln, NE 68583 USA.
EM szhang3@unl.edu
RI Chen, Huann-Sheng/D-6328-2013
OI Chen, Huann-Sheng/0000-0002-5905-8050
NR 15
TC 4
Z9 4
U1 0
U2 27
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-3758
J9 J STAT PLAN INFER
JI J. Stat. Plan. Infer.
PD APR
PY 2013
VL 143
IS 4
BP 764
EP 770
DI 10.1016/j.jspi.2012.10.004
PG 7
WC Statistics & Probability
SC Mathematics
GA 079UW
UT WOS:000314198700009
ER
PT J
AU Wade, BSC
Stockman, M
McLaughlin, MJ
Raznahan, A
Lalonde, F
Giedd, JN
AF Wade, Benjamin Seavey Cutler
Stockman, Michael
McLaughlin, Michael Joseph
Raznahan, Armin
Lalonde, Francois
Giedd, Jay Norman
TI Improved corpus callosum area measurements by analysis of adjoining
parasagittal slices
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Power analysis; Coefficient of variation; Sample size
AB The corpus callosum (CC) is a bundle of approximately 180 million axons connecting homologous areas of the left and right cerebral cortex. Because CC projections are topographically organized, regional CC morphological abnormalities may reflect regional cortical developmental abnormalities. We assess the variance characteristics of three CC area measurement techniques by comparing a single midsagittal slice versus three slices (midsagittal plus one parasagittal on each side) and five slices (midsagittal plus two parasagittal on each side). CC images were partitioned into five subregions using the Hofer-Frahm scheme under the three methods and variance was examined via two complementary data sets. In the first, to control for intersubject variability, 12 scans were acquired from a single subject over the course of 3 h. In the second, we used scans from 56 healthy male volunteers between the ages of 10 and 27 years (mean=17.47, S.D.=3.42). Increasing the number of slices from one to three to five diminished the coefficient of variation (CV) within subregions and increased the power to detect differences between groups. A power analysis was conducted for the sample under each method to determine the sample size necessary to discern a given percent change (delta) ranging from 1 to 20% iteratively. Published by Elsevier Ireland Ltd.
C1 [Wade, Benjamin Seavey Cutler; Stockman, Michael; McLaughlin, Michael Joseph; Raznahan, Armin; Lalonde, Francois; Giedd, Jay Norman] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Wade, BSC (reprint author), NIMH, Child Psychiat Branch, 10 Ctr Dr,MSC 1367,Bldg 10,Room 4C110, Bethesda, MD 20892 USA.
EM benjamin.wade@nih.gov
RI Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978
FU Intramural NIH HHS [Z99 MH999999]
NR 6
TC 2
Z9 3
U1 1
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD MAR 30
PY 2013
VL 211
IS 3
BP 221
EP 225
DI 10.1016/j.pscychresns.2012.05.004
PG 5
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 123HN
UT WOS:000317379100005
PM 23149042
ER
PT J
AU Zhang, LM
Alter, HJ
Wang, HP
Jia, SZ
Wang, E
Marincola, FM
Shih, JWK
Wang, RY
AF Zhang, Lumin
Alter, Harvey J.
Wang, Haiping
Jia, Shuaizheng
Wang, Ena
Marincola, Francesco M.
Shih, James W. -K.
Wang, Richard Y.
TI The modulation of hepatitis C virus 1a replication by PKR is dependent
on NF-kB mediated interferon beta response in Huh7.5.1 cells
SO VIROLOGY
LA English
DT Article
DE PKR silencing; NF-kB activation; IFN-beta; HCV1a replication
ID PROTEIN-KINASE PKR; I-KAPPA-B; IMMORTALIZED HUMAN HEPATOCYTES; CORE
PROTEIN; CULTURE-SYSTEM; RNA; ACTIVATION; EXPRESSION; INFECTION; IFN
AB Protein kinase R (PKR), a sensor of double-stranded RNA, plays an important role in the host response to viral infection. Hepatitis C genotype 2a virus (HCV2a) has been shown to induce PKR activation to suppress the translation of antiviral interferon stimulated genes (ISGs), suggesting that PKR inhibitor can be beneficial for treating chronically HCV-infected patients in conjunction with interferon alpha and ribavirin. However, in this study, we found that PKR inhibition using siRNA PKR, shRNA PKR or PKR inhibitor enhanced HCV 1 a replication and rendered Huh7.5.1 cells more susceptible to HCV1a infection. Additionally, PKR silencing suppressed NF-kB activation and NF-kB mediated STAT1 phosphorylation in Huh7.5.1 cells and HCV1a persistently infected Huh7.5.1 cells (2HDD4). These effects were accompanied by a reduction of interferon beta response and thereby enhanced HCV1a replication in Huh7.5.1 cells. We conclude that host cells can employ PKR activation to restrict HCV1a replication through regulation of NF-kB expression. Published by Elsevier Inc.
C1 [Zhang, Lumin; Alter, Harvey J.; Wang, Ena; Marincola, Francesco M.; Wang, Richard Y.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Wang, Ena; Marincola, Francesco M.] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA.
[Wang, Haiping] Acad Mil Med Sci, Affiliated Hosp, Dept Transfus Med, Beijing, Peoples R China.
[Jia, Shuaizheng] Beijing Inst Transfus Med, Beijing, Peoples R China.
[Shih, James W. -K.] Xiamen Univ, Natl Inst Diagnost & Vaccine Dev Infect Dis, Xiamen, Peoples R China.
RP Wang, RY (reprint author), NIH, Dept Transfus Med, Bldg 10,Room 1C-711,10 Ctr Dr, Bethesda, MD 20892 USA.
EM rwang@cc.nih.gov
FU Warren G. Magnuson Clinical Center, NIH Intramural Research Program
FX This study was supported by the Warren G. Magnuson Clinical Center, NIH
Intramural Research Program. We thank Dr. Francis Chisari for providing
us with Huh7.5.1 cells, Dr. Stanley Lemon for providing us with H77S
plasmids, and Dr. Keijei Mitamura for providing us with IMY-4 and IMY-N9
cell lines. We would also like to appreciate the help from Dr. Liang
Jack and Dr. Li Qisheng. They kindly provided JFH1 virus and JFH1/1a
chimeric virus. We also greatly appreciated Dr. Sonia Voiculescu's
assistance in the review of manuscript.
NR 44
TC 8
Z9 9
U1 0
U2 13
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 MAR 30
PY 2013
VL 438
IS 1
BP 28
EP 36
DI 10.1016/j.virol.2013.01.015
PG 9
WC Virology
SC Virology
GA 104ZW
UT WOS:000316036400005
PM 23399035
ER
PT J
AU Malecka, KA
Szentpetery, Z
Peterson, JR
AF Malecka, Kimberly A.
Szentpetery, Zsofia
Peterson, Jeffrey R.
TI Synergistic Activation of p21-activated Kinase 1 by Phosphatidylinositol
4,5-Bisphosphate and Rho GTPases
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID RECEPTOR SIGNALING COMPLEXES; PROTEIN-KINASE; N-WASP; PTDINS(4,5)P-2
SYNTHESIS; PLASMA-MEMBRANE; ARP2/3 COMPLEX; CELL POLARITY; LIVING CELLS;
CDC42; ACTIN
AB Autoinhibited p21-activated kinase 1 (Pak1) can be activated in vitro by the plasma membrane-bound Rho GTPases Rac1 and Cdc42 as well as by the lipid phosphatidylinositol (4,5)-bisphosphate (PIP2). Activator binding is mediated by a GTPase-binding motif and an adjacent phosphoinositide-binding motif. Whether these two classes of activators play alternative, additive, or synergistic roles in Pak1 activation is unknown, as is their contributions to Pak1 activation in vivo. To address these questions, we developed a system to mimic the membrane anchoring of Rho GTPases by creating liposomes containing both PIP2 and a Ni2+-NTA modified lipid capable of binding hexahistidine-tagged Cdc42. We find that among all biologically relevant phosphoinositides, only PIP2 is able to synergistically activate Pak1 in concert with Cdc42. Membrane binding of the kinase was highly sensitive to the spatial density of PIP2 and Pak1 demonstrated dramatically enhanced affinity for Cdc42 anchored in a PIP2 environment. To validate these findings in vivo, we utilized an inducible recruitment system to drive the ectopic synthesis of PIP2 on Golgi membranes, which normally have active Cdc42 but lack significant concentrations of PIP2. Pak1 was recruited to PIP2-containing membranes in a manner dependent on the ability of Pak1 to bind to both PIP2 and Cdc42. These findings provide a mechanistic explanation for the essential role of both phosphoinositides and GTPases in Pak1 recruitment and activation. In contrast, Ack, another Cdc42 effector kinase that lacks an analogous phosphoinositide-binding motif, fails to show the same enhancement of membrane binding and activation by PIP2, thus indicating that regulation by PIP2 and Cdc42 could provide a combinatorial code for activation of different GTPase effectors in different subcellular locations.
C1 [Malecka, Kimberly A.; Peterson, Jeffrey R.] Fox Chase Canc Ctr, Canc Biol Program, Philadelphia, PA 19111 USA.
[Szentpetery, Zsofia] Eunice Kennedy Shriver NICHD, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Peterson, JR (reprint author), 333 Cottman Ave, Philadelphia, PA 19111 USA.
EM Jeffrey.peterson@fccc.edu
FU National Institutes of Health [GM083025, T32 CA009035, P30 CA006927];
FCCC Keystone Program in Head Neck Cancer
FX This work was supported, in whole or in part, by National Institutes of
Health Grants GM083025 (to J. R. P.), T32 CA009035 (to K. Malecka), and
P30 CA006927 to the Fox Chase Cancer Center. Additional support was
provided by the FCCC Keystone Program in Head & Neck Cancer.
NR 61
TC 4
Z9 4
U1 0
U2 9
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 MAR 29
PY 2013
VL 288
IS 13
BP 8887
EP 8897
DI 10.1074/jbc.M112.428904
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 116DG
UT WOS:000316862200010
PM 23393142
ER
PT J
AU Phillips, DD
Fattah, RJ
Crown, D
Zhang, Y
Liu, SH
Moayeri, M
Fischer, ER
Hansen, BT
Ghirlando, R
Nestorovich, EM
Wein, AN
Simons, L
Leppla, SH
Leysath, CE
AF Phillips, Damilola D.
Fattah, Rasem J.
Crown, Devorah
Zhang, Yi
Liu, Shihui
Moayeri, Mahtab
Fischer, Elizabeth R.
Hansen, Bryan T.
Ghirlando, Rodolfo
Nestorovich, Ekaterina M.
Wein, Alexander N.
Simons, Lacy
Leppla, Stephen H.
Leysath, Clinton E.
TI Engineering Anthrax Toxin Variants That Exclusively Form Octamers and
Their Application to Targeting Tumors
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID STAPHYLOCOCCAL ALPHA-HEMOLYSIN; PROTECTIVE ANTIGEN; LETHAL FACTOR;
SEDIMENTATION-VELOCITY; MAMMALIAN-CELLS; PORE FORMATION; KINASE-KINASE;
OLIGOMERIZATION; ULTRACENTRIFUGATION; INTERNALIZATION
AB Anthrax toxin protective antigen (PA) delivers its effector proteins into the host cell cytosol through formation of an oligomeric pore, which can assume heptameric or octameric states. By screening a highly directed library of PA mutants, we identified variants that complement each other to exclusively form octamers. These PA variants were individually nontoxic and demonstrated toxicity only when combined with their complementary partner. We then engineered requirements for activation by matrix metalloproteases and urokinase plasminogen activator into two of these variants. The resulting therapeutic toxin specifically targeted cells expressing both tumor associated proteases and completely stopped tumor growth in mice when used at a dose far below that which caused toxicity. This scheme for obtaining intercomplementing subunits can be employed with other oligomeric proteins and potentially has wide application.
C1 [Phillips, Damilola D.; Fattah, Rasem J.; Crown, Devorah; Zhang, Yi; Liu, Shihui; Moayeri, Mahtab; Wein, Alexander N.; Simons, Lacy; Leppla, Stephen H.; Leysath, Clinton E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Fischer, Elizabeth R.; Hansen, Bryan T.] NIAID, Electron Microscopy Unit, Res Technol Branch, NIH, Hamilton, MT 59840 USA.
[Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Nestorovich, Ekaterina M.] Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA.
RP Leysath, CE (reprint author), NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM leysathce@niaid.nih.gov
FU Intramural Research Program of NIAID from the National Institutes of
Health; Intramural Research Program of NIDDK from the National
Institutes of Health
FX This work was supported in part by the Intramural Research Programs of
NIAID and NIDDK from the National Institutes of Health.
NR 32
TC 13
Z9 14
U1 1
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 29
PY 2013
VL 288
IS 13
BP 9058
EP 9065
DI 10.1074/jbc.M113.452110
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 116DG
UT WOS:000316862200025
PM 23393143
ER
PT J
AU Corpe, CP
Eck, P
Wang, J
Al-Hasani, H
Levine, M
AF Corpe, Christopher P.
Eck, Peter
Wang, Jin
Al-Hasani, Hadi
Levine, Mark
TI Intestinal Dehydroascorbic Acid (DHA) Transport Mediated by the
Facilitative Sugar Transporters, GLUT2 and GLUT8
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID L-ASCORBIC-ACID; ISOLATED RAT ADIPOCYTES; VITAMIN-C; GLUCOSE
TRANSPORTERS; HEXOSE TRANSPORTERS; XENOPUS OOCYTES; IRON-METABOLISM;
MOUSE; CELLS; INHIBITION
AB Intestinal vitamin C (Asc) absorption was believed to be mediated by the Na+-dependent ascorbic acid transporter SVCT1. However, Asc transport across the intestines of SVCT1 knockout mice is normal indicating that alternative ascorbic acid transport mechanisms exist. To investigate these mechanisms, rodents were gavaged with Asc or its oxidized form dehydroascorbic acid (DHA), and plasma Asc concentrations were measured. Asc concentrations doubled following DHA but not Asc gavage. We hypothesized that the transporters responsible were facilitated glucose transporters (GLUTs). Using Xenopus oocyte expression, we investigated whether facilitative glucose transporters GLUT2 and GLUT5-12 transported DHA. Only GLUT2 and GLUT8, known to be expressed in intestines, transported DHA with apparent transport affinities (K-m) of 2.33 and 3.23 mM and maximal transport rates (V-max) of 25.9 and 10.1 pmol/min/oocyte, respectively. Maximal rates for DHA transport mediated by GLUT2 and GLUT8 in oocytes were lower than maximal rates for 2-deoxy-D-glucose (V-max of 224 and 32 pmol/min/oocyte for GLUT2 and GLUT8, respectively) and fructose (V-max of 406 and 116 pmol/min/oocyte for GLUT2 and GLUT8, respectively). These findings may be explained by differences in the exofacial binding of substrates, as shown by inhibition studies with ethylidine glucose. DHA transport activity in GLUT2- and GLUT8-expressing oocytes was inhibited by glucose, fructose, and by the flavonoids phloretin and quercetin. These studies indicate intestinal DHA transport may be mediated by the facilitative sugar transporters GLUT2 and GLUT8. Furthermore, dietary sugars and flavonoids in fruits and vegetables may modulate Asc bioavailability via inhibition of small intestinal GLUT2 and GLUT8.
C1 [Corpe, Christopher P.; Eck, Peter; Wang, Jin; Al-Hasani, Hadi; Levine, Mark] NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
RP Corpe, CP (reprint author), Kings Coll London, Diabet & Nutr Sci Div, Sch Med, Room 3-114,Franklin Wilkins Bldg,150 Stamford St, London SE1 9NH, England.
RI WANG, Jin/A-8327-2012;
OI WANG, Jin/0000-0002-0062-2489; Eck, Peter/0000-0003-2371-9774
FU National Institutes of Health Intramural Research Program Grant from
NIDDK [DK054506-15]
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Research Program Grant DK054506-15 from NIDDK.
NR 33
TC 25
Z9 25
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 MAR 29
PY 2013
VL 288
IS 13
BP 9092
EP 9101
DI 10.1074/jbc.M112.436790
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 116DG
UT WOS:000316862200029
PM 23396969
ER
PT J
AU Kong, E
Peng, SY
Chandra, G
Sarkar, C
Zhang, ZJ
Bagh, MB
Mukherjee, AB
AF Kong, Eryan
Peng, Shiyong
Chandra, Goutam
Sarkar, Chinmoy
Zhang, Zhongjian
Bagh, Maria B.
Mukherjee, Anil B.
TI Dynamic Palmitoylation Links Cytosol-Membrane Shuttling of Acyl-protein
Thioesterase-1 and Acyl-protein Thioesterase-2 with That of
Proto-oncogene H-Ras Product and Growth-associated Protein-43
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NEURONAL DEVELOPMENT; LYSOPHOSPHOLIPASE I; MOLECULAR-CLONING;
EXPRESSION; IDENTIFICATION; LOCALIZATION; PURIFICATION; PALMITATE;
ACYLATION
AB Acyl-protein thioesterase-1 (APT1) and APT2 are cytosolic enzymes that catalyze depalmitoylation of membrane-anchored, palmitoylated H-Ras and growth-associated protein-43 (GAP-43), respectively. However, the mechanism(s) of cytosol-membrane shuttling of APT1 and APT2, required for depalmitoylating their substrates H-Ras and GAP-43, respectively, remained largely unknown. Here, we report that both APT1 and APT2 undergo palmitoylation on Cys-2. Moreover, blocking palmitoylation adversely affects membrane localization of both APT1 and APT2 and that of their substrates. We also demonstrate that APT1 not only catalyzes its own depalmitoylation but also that of APT2 promoting dynamic palmitoylation (palmitoylation-depalmitoylation) of both thioesterases. Furthermore, shRNA suppression of APT1 expression or inhibition of its thioesterase activity by palmostatin B markedly increased membrane localization of APT2, and shRNA suppression of APT2 had virtually no effect on membrane localization of APT1. In addition, mutagenesis of the active site Ser residue to Ala (S119A), which renders catalytic inactivation of APT1, also increased its membrane localization. Taken together, our findings provide insight into a novel mechanism by which dynamic palmitoylation links cytosol-membrane trafficking of APT1 and APT2 with that of their substrates, facilitating steady- state membrane localization and function of both.
C1 [Kong, Eryan; Peng, Shiyong; Chandra, Goutam; Sarkar, Chinmoy; Zhang, Zhongjian; Bagh, Maria B.; Mukherjee, Anil B.] Eunice Kennedy Shriver NICHD, Sect Dev Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Mukherjee, AB (reprint author), NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mukherja@exchange.nih.gov
RI Peng, Shiyong/D-6391-2014
OI Peng, Shiyong/0000-0003-0697-3674
FU National Institutes of Health Intramural Program of the Eunice
Kennedy-Shriver NICHD
FX This work was supported in whole by National Institutes of Health
Intramural Program of the Eunice Kennedy-Shriver NICHD.
NR 33
TC 22
Z9 22
U1 0
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 MAR 29
PY 2013
VL 288
IS 13
BP 9112
EP 9125
DI 10.1074/jbc.M112.421073
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 116DG
UT WOS:000316862200031
PM 23396970
ER
PT J
AU Gonzalez-Sancho, JM
Greer, YE
Abrahams, CL
Takigawa, Y
Baljinnyam, B
Lee, KH
Lee, KS
Rubin, JS
Brown, AMC
AF Gonzalez-Sancho, Jose M.
Greer, Yoshimi Endo
Abrahams, Cristina L.
Takigawa, Yutaka
Baljinnyam, Bolormaa
Lee, Kyung Ho
Lee, Kyung S.
Rubin, Jeffrey S.
Brown, Anthony M. C.
TI Functional Consequences of Wnt-induced Dishevelled 2 Phosphorylation in
Canonical and Noncanonical Wnt Signaling
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID STABILIZE BETA-CATENIN; PROTEIN ASSEMBLIES; NEURITE OUTGROWTH; DIX
DOMAIN; PATHWAY; MECHANISM; DROSOPHILA; WINGLESS; CELL; ACTIVATION
AB Dishevelled (Dvl) proteins are intracellular effectors of Wnt signaling that have essential roles in both canonical and noncanonical Wnt pathways. It has long been known that Wnts stimulate Dvl phosphorylation, but relatively little is known about its functional significance. We have previously reported that both Wnt3a and Wnt5a induce Dvl2 phosphorylation that is associated with an electrophoretic mobility shift and loss of recognition by monoclonal antibody 10B5. In the present study, we mapped the 10B5 epitope to a 16-amino acid segment of human Dvl2 (residues 594-609) that contains four Ser/Thr residues. Alanine substitution of these residues (P4m) eliminated the mobility shift induced by either Wnt3a or Wnt5a. The Dvl2 P4m mutant showed a modest increase in canonical Wnt/beta-catenin signaling activity relative to wild type. Consistent with this finding, Dvl2 4Pm preferentially localized to cytoplasmic puncta. In contrast to wild-type Dvl2, however, the P4m mutant was unable to rescue Wnt3a-dependent neurite outgrowth in TC-32 cells following suppression of endogenous Dvl2/3. Earlier work has implicated casein kinase 1 delta/epsilon as responsible for the Dvl mobility shift, and a CK1 delta in vitro kinase assay confirmed that Ser(594), Thr(595), and Ser(597) of Dvl2 are CK1 targets. Alanine substitution of these three residues was sufficient to abrogate the Wnt-dependent mobility shift. Thus, we have identified a cluster of Ser/Thr residues in the C-terminal domain of Dvl2 that are Wnt-induced phosphorylation (WIP) sites. Our results indicate that phosphorylation at the WIP sites reduces Dvl accumulation in puncta and attenuates beta-catenin signaling, whereas it enables noncanonical signaling that is required for neurite outgrowth.
C1 [Gonzalez-Sancho, Jose M.; Abrahams, Cristina L.; Takigawa, Yutaka; Brown, Anthony M. C.] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY 10065 USA.
[Greer, Yoshimi Endo; Baljinnyam, Bolormaa; Rubin, Jeffrey S.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lee, Kyung Ho; Lee, Kyung S.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Brown, AMC (reprint author), Weill Cornell Med Coll, Dept Cell & Dev Biol, 1300 York Ave, New York, NY 10065 USA.
EM amcbrown@med.cornell.edu
OI Gonzalez Sancho, Jose Manuel/0000-0001-5875-1964
FU National Institutes of Health Grant [R01 CA123238]; Ministerio de
Educacion, Cultura, y Deportes, of Spain; New York State Department of
Health postdoctoral Fellowship [NYS C021339]; [F32 CA117662]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant R01 CA123238 (to A. M. C. B.) and Postdoctoral Fellowship
F32 CA117662 (to C. L. A.). This work was also supported by a fellowship
from the Ministerio de Educacion, Cultura, y Deportes, of Spain (to J.
M. G.-S.), by New York State Department of Health postdoctoral
Fellowship NYS C021339 (to Y. T.), and by charitable donations to Strang
Cancer Prevention Center. This research also was supported in part by
the Intramural Research Program of the National Institutes of Health,
National Cancer Institute.
NR 54
TC 18
Z9 18
U1 3
U2 17
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 MAR 29
PY 2013
VL 288
IS 13
BP 9428
EP 9437
DI 10.1074/jbc.M112.448480
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 116DG
UT WOS:000316862200059
PM 23396967
ER
PT J
AU Greer, YE
Fields, AP
Brown, AMC
Rubin, JS
AF Greer, Yoshimi Endo
Fields, Alan P.
Brown, Anthony M. C.
Rubin, Jeffrey S.
TI Atypical Protein Kinase C iota Is Required for Wnt3a-dependent Neurite
Outgrowth and Binds to Phosphorylated Dishevelled 2
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID AXON GUIDANCE; NEURONAL POLARITY; EWINGS-SARCOMA; PKC-ZETA; WNT; CELLS;
RYK; CENTROSOME; PATHWAY; GROWTH
AB Previously we reported that Wnt3a-dependent neurite outgrowth in Ewing sarcoma family tumor cell lines was mediated by Frizzled3, Dishevelled (Dvl), and c-Jun N-terminal kinase (Endo, Y., Beauchamp, E., Woods, D., Taylor, W. G., Toretsky, J. A., Uren, A., and Rubin, J. S. (2008) Mol. Cell. Biol. 28, 2368-2379). Subsequently, we observed that Dvl2/3 phosphorylation correlated with neurite outgrowth and that casein kinase 1 delta, one of the enzymes that mediate Wnt3a-dependent Dvl phosphorylation, was required for neurite extension (Greer, Y. E., and Rubin, J. S. (2011) J. Cell Biol. 192, 993-1004). However, the functional relevance of Dvl phosphorylation in neurite outgrowth was not established. Dvl1 has been shown by others to be important for axon specification in hippocampal neurons via an interaction with atypical PKC zeta, but the role of Dvl phosphorylation was not evaluated. Here we report that Ewing sarcoma family tumor cells express PKC iota but not PKC zeta. Wnt3a stimulated PKC iota activation and caused a punctate distribution of pPKC iota in the neurites and cytoplasm, with a particularly intense signal at the centrosome. Knockdown of PKC iota expression with siRNA reagents blocked neurite formation in response to Wnt3a. Aurothiomalate, a specific inhibitor of PKC iota/Par6 binding, also suppressed neurite extension. Wnt3a enhanced the co-immunoprecipitation of endogenous PKC iota and Dvl2. Although FLAG-tagged wild-type Dvl2 immunoprecipitated with PKC iota, a phosphorylation-deficient Dvl2 derivative did not. This derivative also was unable to rescue neurite outgrowth when endogenous Dvl2/3 was suppressed by siRNA (Gonzalez-Sancho, J. M., Greer, Y. E., Abrahams, C. L., Takigawa, Y., Baljinnyam, B., Lee, K. H., Lee, K. S., Rubin, J. S., and Brown, A. M. (2013) J. Biol. Chem. 288, 9428-9437). Taken together, these results suggest that site-specific Dvl2 phosphorylation is required for Dvl2 association with PKC iota. This interaction is likely to be one of the mechanisms essential for Wnt3a-dependent neurite outgrowth.
C1 [Greer, Yoshimi Endo; Rubin, Jeffrey S.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Fields, Alan P.] Mayo Clin, Coll Med, Dept Canc Biol, Jacksonville, FL 32224 USA.
[Brown, Anthony M. C.] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY 10065 USA.
RP Rubin, JS (reprint author), NCI, Bldg 37,Rm 2042,37 Convent Dr,MSC 4256, Bethesda, MD 20892 USA.
EM rubinj@mail.nih.gov
FU National Institutes of Health [R01 CA123238, R01 CA081436-15];
Intramural Research Program of the National Institutes of Health;
National Cancer Institute; Florida Biomedical Research Program
[KG05-339710-03]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01 CA123238 (to A. M. C. B.) and R01 CA081436-15 (to A.
P. F.). This work was also supported by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute, and
Florida Biomedical Research Program Grant KG05-339710-03 (to A. P. F.).
NR 43
TC 5
Z9 6
U1 1
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 29
PY 2013
VL 288
IS 13
BP 9438
EP 9446
DI 10.1074/jbc.M112.448282
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 116DG
UT WOS:000316862200060
PM 23396968
ER
PT J
AU Guzik-Lendrum, S
Heissler, SM
Billington, N
Takagi, Y
Yang, Y
Knight, PJ
Homsher, E
Sellers, JR
AF Guzik-Lendrum, Stephanie
Heissler, Sarah M.
Billington, Neil
Takagi, Yasuharu
Yang, Yi
Knight, Peter J.
Homsher, Earl
Sellers, James R.
TI Mammalian Myosin-18A, a Highly Divergent Myosin
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TUMOR-SUPPRESSOR GENE; SMOOTH-MUSCLE MYOSIN; PHOSPHORYLATION-DEPENDENT
REGULATION; REGULATORY LIGHT-CHAIN; RABBIT SKELETAL-MUSCLE;
PDZ-CONTAINING MYOSIN; ACTIN-BINDING SITE; HEAVY-MEROMYOSIN; MOTOR
DOMAIN; ADENOSINE-TRIPHOSPHATASE
AB The Mus musculus myosin-18A gene is expressed as two alternatively spliced isoforms, alpha and beta, with reported roles in Golgi localization, in maintenance of cytoskeleton, and as receptors for immunological surfactant proteins. Both myosin-18A isoforms feature a myosin motor domain, a single predicted IQ motif, and a long coiled-coil reminiscent of myosin-2. The myosin-18A alpha isoform, additionally, has an N-terminal PDZ domain. Recombinant heavy meromyosin- and subfragment-1 (S1)-like constructs for both myosin-18A alpha and -18 beta species were purified from the baculovirus/Sf9 cell expression system. These constructs bound both essential and regulatory light chains, indicating an additional noncanonical light chain binding site in the neck. Myosin-18A alpha-S1 and -18A beta-S1 molecules bound actin weakly with K-d values of 4.9 and 54 mu M, respectively. The actin binding data could be modeled by assuming an equilibrium between two myosin conformations, a competent and an incompetent form to bind actin. Actin binding was unchanged by presence of nucleotide. Both myosin-18A isoforms bound N-methylanthraniloyl- nucleotides, but the rate of ATP hydrolysis was very slow (<0.002 s(-1)) and not significantly enhanced by actin. Phosphorylation of the regulatory light chain had no effect on ATP hydrolysis, and neither did the addition of tropomyosin or of GOLPH3, a myosin-18A binding partner. Electron microscopy of myosin-18A-S1 showed that the lever is strongly angled with respect to the long axis of the motor domain, suggesting a pre-power stroke conformation regardless of the presence of ATP. These data lead us to conclude that myosin-18A does not operate as a traditional molecular motor in cells.
C1 [Homsher, Earl; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
[Yang, Yi] Hunan Agr Univ, Coll Vet Med, Lab Funct Prote, Changsha 410128, Hunan, Peoples R China.
[Knight, Peter J.] Univ Leeds, Astbury Ctr Struct Mol Biol, Sch Mol & Cellular Biol, Leeds LS2 9JT, W Yorkshire, England.
[Homsher, Earl] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA.
RP Sellers, JR (reprint author), NHLBI, Lab Mol Physiol, NIH, 50 South Dr,B50-3523, Bethesda, MD 20892 USA.
EM sellersj@nhlbi.nih.gov
OI Billington, Neil/0000-0003-2306-0228
FU Electron Microscopy Core Facility of the NHLBI
FX We thank Fang Zhang for technical assistance with myosin-18A experiments
and protein purification, Melanie Barzik and John A. Hammer III (NHLBI,
National Institutes of Health) for providing a full-length clone of
mouse myosin-18A alpha and -beta as starting points for cloning in this
project, and Kathryn Callahan (NIDDK, National Institutes of Health) for
assistance with filter binding assays. We thank the NHLBI Proteomics
Core Facility, which provided excellent service. We thank the Electron
Microscopy Core Facility of the NHLBI for support and the use of
facilities.
NR 71
TC 23
Z9 23
U1 1
U2 21
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 MAR 29
PY 2013
VL 288
IS 13
BP 9532
EP 9548
DI 10.1074/jbc.M112.441238
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 116DG
UT WOS:000316862200068
PM 23382379
ER
PT J
AU Mardones, GA
Burgos, PV
Lin, Y
Kloer, DP
Magadan, JG
Hurley, JH
Bonifacino, JS
AF Mardones, Gonzalo A.
Burgos, Patricia V.
Lin, Yimo
Kloer, Daniel P.
Magadan, Javier G.
Hurley, James H.
Bonifacino, Juan S.
TI Structural Basis for the Recognition of Tyrosine-based Sorting Signals
by the mu 3A Subunit of the AP-3 Adaptor Complex
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CLATHRIN-ASSOCIATED PROTEINS; LYSOSOMAL MEMBRANE-PROTEINS;
HERMANSKY-PUDLAK-SYNDROME; MEDIUM CHAINS; ENDOCYTIC MACHINERY;
CYTOPLASMIC TAIL; BETA-3A SUBUNIT; AP2 COMPLEX; RECEPTOR; BINDING
AB Tyrosine-based signals fitting the YXX empty set motif mediate sorting of transmembrane proteins to endosomes, lysosomes, the basolateral plasma membrane of polarized epithelial cells, and the somatodendritic domain of neurons through interactions with the homologous mu 1, mu 2, mu 3, and mu 4 subunits of the corresponding AP-1, AP-2, AP-3, and AP-4 complexes. Previous x-ray crystallographic analyses identified distinct binding sites for YXX empty set signals on mu 2 and mu 4, which were located on opposite faces of the proteins. To elucidate the mode of recognition of YXX empty set signals by other members of the mu family, we solved the crystal structure at 1.85 angstrom resolution of the C-terminal domain of the mu 3 subunit of AP-3 (isoform A) in complex with a peptide encoding a YXX empty set signal (SDYQRL) from the trans-Golgi network protein TGN38. The mu 3A C-terminal domain consists of an immunoglobulin-like beta-sandwich organized into two sub-domains, A and B. The YXX empty set signal binds in an extended conformation to a site on mu 3A subdomain A, at a location similar to the YXX empty set -binding site on mu 2 but not mu 4. The binding sites on mu 3A and mu 2 exhibit similarities and differences that account for the ability of both proteins to bind distinct sets of YXX empty set signals. Biochemical analyses confirm the identification of the mu 3A site and show that this protein binds YXX empty set signals with 14-19 mu M affinity. The surface electrostatic potential of mu 3A is less basic than that of mu 2, in part explaining the association of AP-3 with intracellular membranes having less acidic phosphoinositides.
C1 [Mardones, Gonzalo A.; Burgos, Patricia V.] Univ Austral Chile, Inst Fisiol, Fac Med, Valdivia 5110566, Chile.
[Mardones, Gonzalo A.; Burgos, Patricia V.] Univ Austral Chile, Ctr Invest Sur Austral Enfermedades Sistema Nervi, Valdivia 5110566, Chile.
[Mardones, Gonzalo A.; Burgos, Patricia V.; Lin, Yimo; Magadan, Javier G.; Bonifacino, Juan S.] NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Kloer, Daniel P.; Hurley, James H.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Mardones, GA (reprint author), Univ Austral Chile, Inst Fisiol, Fac Med, Valdivia 5110566, Chile.
EM gonzalo.mardones@uach.cl; hurley@helix.nih.gov; juan@helix.nih.gov
FU Fondo Nacional de Desarrollo Cientifico y Tecnologico of Chile
[1100896]; Intramural Program of NICHD, National Institutes of Health;
Intramural Program of NIDDK, National Institutes of Health; U. S.
Department of Energy, Basic Energy Sciences, Office of Science
[W-31-109-Eng-38]
FX This work was supported by Grant 1100896 from Fondo Nacional de
Desarrollo Cientifico y Tecnologico of Chile (to G. A. M.), and the
Intramural Programs of NICHD (to J. S. B.) and NIDDK (to J. H. H.),
National Institutes of Health. Use of 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 48
TC 14
Z9 14
U1 0
U2 11
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 MAR 29
PY 2013
VL 288
IS 13
BP 9563
EP 9571
DI 10.1074/jbc.M113.450775
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 116DG
UT WOS:000316862200070
PM 23404500
ER
PT J
AU Lionakis, MS
Holland, SM
AF Lionakis, Michail S.
Holland, Steven M.
TI CARD9: at the intersection of mucosal and systemic antifungal immunity
SO BLOOD
LA English
DT Editorial Material
ID DECTIN-1
C1 [Lionakis, Michail S.; Holland, Steven M.] NIH, Bethesda, MD 20892 USA.
RP Lionakis, MS (reprint author), NIH, Bethesda, MD 20892 USA.
NR 10
TC 5
Z9 5
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 MAR 28
PY 2013
VL 121
IS 13
BP 2377
EP 2378
DI 10.1182/blood-2013-01-480434
PG 4
WC Hematology
SC Hematology
GA 182RT
UT WOS:000321762400004
PM 23538230
ER
PT J
AU Gotlib, J
Pardanani, A
Akin, C
Reiter, A
George, T
Hermine, O
Kluin-Nelemans, H
Hartmann, K
Sperr, WR
Brockow, K
Schwartz, LB
Orfao, A
DeAngelo, DJ
Arock, M
Sotlar, K
Horny, HP
Metcalfe, DD
Escribano, L
Verstovsek, S
Tefferi, A
Valent, P
AF Gotlib, Jason
Pardanani, Animesh
Akin, Cem
Reiter, Andreas
George, Tracy
Hermine, Olivier
Kluin-Nelemans, Hanneke
Hartmann, Karin
Sperr, Wolfgang R.
Brockow, Knut
Schwartz, Lawrence B.
Orfao, Alberto
DeAngelo, Daniel J.
Arock, Michel
Sotlar, Karl
Horny, Hans-Peter
Metcalfe, Dean D.
Escribano, Luis
Verstovsek, Srdan
Tefferi, Ayalew
Valent, Peter
TI International Working Group-Myeloproliferative Neoplasms Research and
Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM)
consensus response criteria in advanced systemic mastocytosis
SO BLOOD
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; MAST-CELL LEUKEMIA;
OF-THE-LITERATURE; PHASE-II TRIAL; C-KIT MUTATION; INTERFERON-ALPHA;
IMATINIB MESYLATE; SPANISH NETWORK; CLADRIBINE
AB Systemic mastocytosis (SM) is characterized by accumulation of neoplastic mast cells and is classified into indolent and aggressive forms. The latter include aggressive SM (ASM), mast cell leukemia (MCL), and SM associated with a myeloid neoplasm wherein 1 or both disease compartments exhibit advanced features. These variants, henceforth collectively referred to as advanced SM for the purposes of this report, are typically characterized by organ damage and shortened survival duration. In contrast to indolent SM, in which symptoms are usually managed by noncytotoxic antimediator therapy, cytoreduction is usually necessary for disease control in advanced SM. Unfortunately, current drug treatment of these patients rarely results in complete clinical and histopathologic remissions or improved survival time. Previously defined response criteria were adapted to the heterogeneous presentations of advanced SM and the limited effects of available drugs. However, recent advances in understanding the molecular pathogenesis of SM and the corresponding prospect in targeted therapy make it a priority to modify these criteria. Our current study is the product of an international group of experts and summarizes the challenges in accomplishing this task and forwards a new proposal for response criteria, which builds on prior proposals and should facilitate response evaluation in clinical trials.
C1 [Gotlib, Jason; George, Tracy] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Pardanani, Animesh; Tefferi, Ayalew] Mayo Clin, Rochester, MN USA.
[Akin, Cem] Harvard Univ, Sch Med, Boston, MA USA.
[Akin, Cem] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Reiter, Andreas] Univ Med Mannheim, Med Klin 3, Mannheim, Germany.
[Hermine, Olivier] Paris Descartes Univ, CNRS, Unite Mixte Rech 8147, Paris, France.
[Hermine, Olivier] Paris Descartes Univ, Necker Hosp, Paris, France.
[Kluin-Nelemans, Hanneke] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
[Hartmann, Karin] Univ Cologne, D-50931 Cologne, Germany.
[Sperr, Wolfgang R.; Valent, Peter] Med Univ Vienna, Vienna, Austria.
[Brockow, Knut] Biederstein Tech Univ, Munich, Germany.
[Schwartz, Lawrence B.] Virginia Commonwealth Univ, Richmond, VA USA.
[Orfao, Alberto; Escribano, Luis] Univ Salamanca, E-37008 Salamanca, Spain.
[DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Arock, Michel] Grp Hosp Pitie Salpetriere, Cent Hematol Lab, F-75634 Paris, France.
[Arock, Michel] Ecole Normale Super, LBPA, CNRS UMR 8113, F-75231 Paris, France.
[Sotlar, Karl; Horny, Hans-Peter] Univ Munich, Munich, Germany.
[Metcalfe, Dean D.] NIAID, NIH, Bethesda, MD 20892 USA.
[Verstovsek, Srdan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Gotlib, J (reprint author), Stanford Canc Inst, 875 Blake Wilbur Dr,Room 2324, Stanford, CA 94305 USA.
EM jason.gotlib@stanford.edu
RI Hartmann, Karin/N-4865-2015;
OI Hartmann, Karin/0000-0002-4595-8226; Akin, Cem/0000-0001-6301-4520
FU Charles and Ann Johnson Foundation; Division of Intramural Research,
NIAID, National Institutes of Health; Ministerio de Sanidad y Asuntos
Sociales [FIS PS09/00032]; Austrian Science Fund (FWF) SFB-project
[F4704-B20]
FX This work was supported in part by the Charles and Ann Johnson
Foundation (J.G.), the Division of Intramural Research, NIAID, National
Institutes of Health (D. D. M), a grant by the Ministerio de Sanidad y
Asuntos Sociales (FIS PS09/00032) (L. E.), and by the Austrian Science
Fund (FWF) SFB-project F4704-B20.
NR 58
TC 35
Z9 35
U1 0
U2 7
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 MAR 28
PY 2013
VL 121
IS 13
BP 2393
EP 2401
DI 10.1182/blood-2012-09-458521
PG 9
WC Hematology
SC Hematology
GA 182RT
UT WOS:000321762400009
PM 23325841
ER
PT J
AU Muranski, P
Restifo, NP
AF Muranski, Pawel
Restifo, Nicholas P.
TI Essentials of Th17 cell commitment and plasticity
SO BLOOD
LA English
DT Review
ID GRAFT-VERSUS-HOST; ROR-GAMMA-T; TRANSCRIPTION FACTOR GATA-3;
INFLAMMATORY-BOWEL-DISEASE; PATHOGENIC T(H)17 CELLS; PROMOTE
TUMOR-GROWTH; CYTOKINE GM-CSF; TGF-BETA; IN-VIVO; HELPER-CELLS
AB CD4(+) T helper (Th) cells exist in a variety of epigenetic states that determine their function, phenotype, and capacity for persistence. These polarization states include Th1, Th2, Th17, and Foxp3(+) T regulatory cells, as well as the more recently described T follicular helper, Th9, and Th22 cells. Th17 cells express the master transcriptional regulator retinoic acid-related orphan receptor gamma thymus and produce canonical interleukin (IL)-17A and IL-17F cytokines. Th17 cells display a great degree of context-dependent plasticity, as they are capable of acquiring functional characteristics of Th1 cells. This late plasticity may contribute to the protection against microbes, plays a role in the development of autoimmunity, and is necessary for antitumor activity of Th17 cells in adoptive cell transfer therapy models. Moreover, plasticity of this subset is associated with higher in vivo survival and self-renewal capacity and less senescence than Th1 polarized cells, which have less plasticity and more phenotypic stability. New findings indicate that subset polarization of CD4(+) T cells not only induces characteristic patterns of surface markers and cytokine production but also has a maturational aspect that affects a cell's ability to survive, respond to secondary stimulation, and form long-term immune memory.
C1 [Muranski, Pawel] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Restifo, Nicholas P.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Muranski, P (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr,3E-5288, Bethesda, MD 20892 USA.
EM muranskp@mail.nih.gov
OI Restifo, Nicholas P./0000-0003-4229-4580
FU Center for Cancer Research, National Cancer Institute-National
Institutes of Health; National Heart, Lung, and Blood Institute;
National Institutes of Health Center for Regenerative Medicine
FX This work was supported by the Center for Cancer Research, National
Cancer Institute-National Institutes of Health Intramural Research
Program, the National Heart, Lung, and Blood Institute Intramural
Program, and the National Institutes of Health Center for Regenerative
Medicine.
NR 204
TC 113
Z9 121
U1 5
U2 38
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 MAR 28
PY 2013
VL 121
IS 13
BP 2402
EP 2414
DI 10.1182/blood-2012-09-378653
PG 13
WC Hematology
SC Hematology
GA 182RT
UT WOS:000321762400010
PM 23325835
ER
PT J
AU Yang, CZ
Sun, MG
Matro, J
Huynh, TT
Rahimpour, S
Prchal, JT
Lechan, R
Lonser, R
Pacak, K
Zhuang, ZP
AF Yang, Chunzhang
Sun, Michael G.
Matro, Joey
Huynh, Thanh T.
Rahimpour, Shervin
Prchal, Josef T.
Lechan, Ronald
Lonser, Russell
Pacak, Karel
Zhuang, Zhengping
TI Novel HIF2A mutations disrupt oxygen sensing, leading to polycythemia,
paragangliomas, and somatostatinomas
SO BLOOD
LA English
DT Article
ID HYPOXIA-INDUCIBLE FACTOR; GENE; ERYTHROCYTOSIS; HYDROXYLATION;
HIF-2-ALPHA; INHIBITION; PROTEIN
AB Hypoxia-inducible factors (HIFs) control the cellular response to hypoxia and, when dysregulated, contribute to tumorigenesis. Previously, we identified 2 gain-of-function somatic mutations in patients presenting with multiple paragangliomas or somatostatinomas, and polycythemia. Here, we report 2 additional unique HIF2A mutations, which disrupt the hydroxylation domain recognized by prolyl hydroxylase domain-2 containing protein, leading to stabilization of HIF-2 alpha and increased expression of hypoxia-related genes.
C1 [Yang, Chunzhang; Sun, Michael G.; Rahimpour, Shervin; Lonser, Russell; Zhuang, Zhengping] NINDS, NIH, Surg Neurol Branch, Bethesda, MD 20894 USA.
[Matro, Joey; Huynh, Thanh T.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Prchal, Josef T.] Associated Reg & Univ Pathologists & Vet Adm Hosp, Div Hematol, Salt Lake City, UT USA.
[Prchal, Josef T.] Univ Utah, Sch Med, Eccles Inst Human Genet, Salt Lake City, UT USA.
[Lechan, Ronald] Tufts Med Ctr, Div Endocrinol, Boston, MA USA.
RP Zhuang, ZP (reprint author), NINDS, NIH, 9000 Rockville Pike,Bldg 10,Room 7N246, Bethesda, MD 20894 USA.
EM karel@mail.nih.gov; zhuangp@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke; Eunice Kennedy
Shriver National Institute of Child Health and Human Development
FX This work was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke and the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development.
NR 14
TC 31
Z9 31
U1 1
U2 11
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 MAR 28
PY 2013
VL 121
IS 13
BP 2563
EP 2566
DI 10.1182/blood-2012-10-460972
PG 4
WC Hematology
SC Hematology
GA 182RT
UT WOS:000321762400027
PM 23361906
ER
PT J
AU Wuchty, S
Vazquez, A
Bozdag, S
Bauer, PO
AF Wuchty, Stefan
Vazquez, Alexei
Bozdag, Serdar
Bauer, Peter O.
TI Genome-wide associations of signaling pathways in glioblastoma
multiforme
SO BMC MEDICAL GENOMICS
LA English
DT Article
ID GLOBAL GENE-EXPRESSION; COPY-NUMBER ALTERATION; CORE PATHWAYS; CANCER;
DISEASE; GLIOMA; DISCOVERY; PROFILES; SUBTYPES; REVEALS
AB Background: eQTL analysis is a powerful method that allows the identification of causal genomic alterations, providing an explanation of expression changes of single genes. However, genes mediate their biological roles in groups rather than in isolation, prompting us to extend the concept of eQTLs to whole gene pathways.
Methods: We combined matched genomic alteration and gene expression data of glioblastoma patients and determined associations between the expression of signaling pathways and genomic copy number alterations with a non-linear machine learning approach.
Results: Expectedly, over-expressed pathways were largely associated to tag-loci on chromosomes with signature alterations. Surprisingly, tag-loci that were associated to under-expressed pathways were largely placed on other chromosomes, an observation that held for composite effects between chromosomes as well. Indicating their biological relevance, identified genomic regions were highly enriched with genes having a reported driving role in gliomas. Furthermore, we found pathways that were significantly enriched with such driver genes.
Conclusions: Driver genes and their associated pathways may represent a functional core that drive the tumor emergence and govern the signaling apparatus in GBMs. In addition, such associations may be indicative of drug combinations for the treatment of brain tumors that follow similar patterns of common and diverging alterations.
C1 [Wuchty, Stefan] Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA.
[Vazquez, Alexei] Canc Inst New Jersey, Dept Radiat Oncol, New Brunswick, NJ 08901 USA.
[Vazquez, Alexei] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ 08901 USA.
[Bozdag, Serdar] Marquette Univ, Dept Math Stat & Comp Sci, Milwaukee, WI 53233 USA.
[Bauer, Peter O.] Natl Canc Inst, Natl Inst Hlth, NINDS, Bethesda, MD 20892 USA.
RP Wuchty, S (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA.
EM wuchtys@ncbi.nlm.nih.gov
FU National Institutes of Health/Department of Health and Human Service
(DHHS) (Intramural Research program of the National Library of Medicine)
FX This work was supported by the National Institutes of Health/Department
of Health and Human Service (DHHS) (Intramural Research program of the
National Library of Medicine).
NR 45
TC 2
Z9 2
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1755-8794
J9 BMC MED GENOMICS
JI BMC Med. Genomics
PD MAR 28
PY 2013
VL 6
AR 11
DI 10.1186/1755-8794-6-11
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 124MK
UT WOS:000317468300001
PM 23537212
ER
PT J
AU Klein, F
Diskin, R
Scheid, JF
Gaebler, C
Mouquet, H
Georgiev, IS
Pancera, M
Zhou, TQ
Incesu, RB
Fu, BZ
Gnanapragasam, PNP
Oliveira, TY
Seaman, MS
Kwong, PD
Bjorkman, PJ
Nussenzweig, MC
AF Klein, Florian
Diskin, Ron
Scheid, Johannes F.
Gaebler, Christian
Mouquet, Hugo
Georgiev, Ivelin S.
Pancera, Marie
Zhou, Tongqing
Incesu, Reha-Baris
Fu, Brooks Zhongzheng
Gnanapragasam, Priyanthi N. P.
Oliveira, Thiago Y.
Seaman, Michael S.
Kwong, Peter D.
Bjorkman, Pamela J.
Nussenzweig, Michel C.
TI Somatic Mutations of the Immunoglobulin Framework Are Generally Required
for Broad and Potent HIV-1 Neutralization
SO CELL
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; MEMORY
B-CELLS; CHIMERIC VIRUS; 3-DIMENSIONAL STRUCTURE; RATIONAL DESIGN;
DOMAIN EXCHANGE; CD4 BINDING; ANTIGEN; EPITOPE
AB Broadly neutralizing antibodies (bNAbs) to HIV-1 can prevent infection and are therefore of great importance for HIV-1 vaccine design. Notably, bNAbs are highly somatically mutated and generated by a fraction of HIV-1-infected individuals several years after infection. Antibodies typically accumulate mutations in the complementarity determining region (CDR) loops, which usually contact the antigen. The CDR loops are scaffolded by canonical framework regions (FWRs) that are both resistant to and less tolerant of mutations. Here, we report that in contrast to most antibodies, including those with limited HIV-1 neutralizing activity, most bNAbs require somatic mutations in their FWRs. Structural and functional analyses reveal that somatic mutations in FWR residues enhance breadth and potency by providing increased flexibility and/or direct antigen contact. Thus, in bNAbs, FWRs play an essential role beyond scaffolding the CDR loops and their unusual contribution to potency and breadth should be considered in HIV-1 vaccine design.
C1 [Klein, Florian; Scheid, Johannes F.; Gaebler, Christian; Mouquet, Hugo; Incesu, Reha-Baris; Oliveira, Thiago Y.; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
[Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
[Diskin, Ron; Fu, Brooks Zhongzheng; Gnanapragasam, Priyanthi N. P.; Bjorkman, Pamela J.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
[Bjorkman, Pamela J.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
[Diskin, Ron] Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel.
[Scheid, Johannes F.] Charite, D-10117 Berlin, Germany.
[Gaebler, Christian] Tech Univ Dresden, Fac Med Carl Gustav Carus, D-01307 Dresden, Germany.
[Georgiev, Ivelin S.; Pancera, Marie; Zhou, Tongqing; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Incesu, Reha-Baris] Univ Klinikum Hamburg Eppendorf, D-20246 Hamburg, Germany.
[Oliveira, Thiago Y.] Univ Sao Paulo, Dept Genet, Med Sch Ribeirao Preto, Natl Inst Sci & Technol Stem Cells & Cell Therapy, BR-14051140 Ribeirao Preto, SP, Brazil.
[Oliveira, Thiago Y.] Ctr Cell Based Therapy, BR-14051140 Ribeirao Preto, SP, Brazil.
[Seaman, Michael S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
RP Nussenzweig, MC (reprint author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
EM nussen@rockefeller.edu
RI Zhou, Tongqing/A-6880-2010; Mouquet, Hugo/M-2750-2014;
OI Zhou, Tongqing/0000-0002-3935-4637; Oliveira, Thiago/0000-0002-2654-0879
FU German Research Foundation (DFG) [KL 2389/1-1]; Stavros Niarchos
Foundation; Robert Mapplethorpe Foundation; German National Academic
Foundation; Vaccine Research Center, NIAID, NIH; Bill and Melinda Gates
Foundation [1032144, 38660, OPP1033115]; CHAVI-ID Award [UM1AI100663];
NIH grant [AI081677]
FX We thank Louise Scharf for her help on generating structural images and
Kai-Hui Yao for technical assistance. We thank Paola Marchovecchio and
Han Gan for preparation of 3BNC60P61A as well as the members
of the Nussenzweig and Bjorkman laboratory for helpful discussions. We
also thank R. Wyatt for the YU2-gp140 plasmid; Davide Corti and Antonio
Lanzavecchia for the HJ16 plasmids, and Francine McCutchan, Beatrice
Hahn, David Montefiori, Michael Thomson, Ronald Swanstrom, Lynn Morris,
Jerome Kim, Linqi Zhang, Dennis Ellenberger, and Carolyn Williamson for
contributing HIV-1 envelope plasmids used in neutralization assays. F.K.
was supported by the German Research Foundation (DFG, KL 2389/1-1), the
Stavros Niarchos Foundation and the Robert Mapplethorpe Foundation. C.G.
and R.-B.I. were supported by The German National Academic Foundation.
I.G., M.P., T.Z., and P.D.K. were supported by intramural funding to the
Vaccine Research Center, NIAID, NIH. M.S.S., P.J.B., and M.C.N. were
supported by the Bill and Melinda Gates Foundation (M.S.S.,
Comprehensive Antibody Vaccine Immune Monitoring Consortium grant
1032144; P.J.B. and M.C.N., Collaboration for AIDS Vaccine Discovery
grants 38660 [P.J.B.] and OPP1033115 [M.C.N.]). M.C.N is supported by
the CHAVI-ID Award UM1AI100663 and The NIH grant AI081677. M.C.N. and
P.J.B. are HHMI investigators.
NR 62
TC 159
Z9 160
U1 2
U2 40
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 28
PY 2013
VL 153
IS 1
BP 126
EP 138
DI 10.1016/j.cell.2013.03.018
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 116AI
UT WOS:000316853700011
PM 23540694
ER
PT J
AU Hou, YJ
Zhao, YY
Xiong, B
Cui, XS
Kim, NH
Xu, YX
Sun, SC
AF Hou, Yan-Jun
Zhao, Yong-Yan
Xiong, Bo
Cui, Xiang-Shun
Kim, Nam-Hyung
Xu, Yin-Xue
Sun, Shao-Chen
TI Mycotoxin-Containing Diet Causes Oxidative Stress in the Mouse
SO PLOS ONE
LA English
DT Article
ID BLOOD PHAGOCYTIC-ACTIVITY; DEOXYNIVALENOL VOMITOXIN;
SUPEROXIDE-DISMUTASE; BALB/C MICE; ZEARALENONE; ANTIOXIDANTS; RATS;
CHICKENS; TOXICITY; BROILERS
AB Mycotoxins which mainly consist of Aflatoxin (AF), Zearalenone (ZEN) and Deoxynivalenol (DON) are commonly found in many food commodities. Although each component has been shown to cause liver toxicity and oxidative stress in several species, there is no evidence regarding the effect of naturally contained multiple mycotoxins on tissue toxicity and oxidative stress in vivo. In the present study, mycotoxins-contaminated maize (AF 597 mu g/kg, ZEN 729 mu g/kg, DON 3.1 mg/kg maize) was incorporated into the diet at three different doses (0, 5 and 20%) to feed the mice, and blood and tissue samples were collected to examine the oxidative stress related indexes. The results showed that the indexes of liver, kidney and spleen were all increased and the liver and kidney morphologies changed in the mycotoxin-treated mice. Also, the treatment resulted in the elevated glutathione peroxidase (GPx) activity and malondialdehyde (MDA) level in the serum and liver, indicating the presence of the oxidative stress. Moreover, the decrease of catalase (CAT) activity in the serum, liver and kidney as well as superoxide dismutase (SOD) activity in the liver and kidney tissue further confirmed the occurrence of oxidative stress. In conclusion, our data indicate that the naturally contained mycotoxins are toxic in vivo and able to induce the oxidant stress in the mouse.
C1 [Hou, Yan-Jun; Zhao, Yong-Yan; Xu, Yin-Xue; Sun, Shao-Chen] Nanjing Agr Univ, Coll Anim Sci & Technol, Nanjing, Jiangsu, Peoples R China.
[Xiong, Bo] NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
[Cui, Xiang-Shun; Kim, Nam-Hyung] Chungbuk Natl Univ, Dept Anim Sci, Cheongju, South Korea.
RP Xu, YX (reprint author), Nanjing Agr Univ, Coll Anim Sci & Technol, Nanjing, Jiangsu, Peoples R China.
EM xuyinxue@njau.edu.cn; sunsc@njau.edu.cn
FU Fundamental Research Funds for the Central Universities [KYRC201202];
Biogreen 21 Program, RDA, Republic of Korea [PJ0090802013, PJ0090982013]
FX This work was supported by the Fundamental Research Funds for the
Central Universities (KYRC201202); and the Biogreen 21 Program
(PJ0090802013, PJ0090982013), RDA, Republic of Korea. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 28
TC 22
Z9 22
U1 3
U2 37
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 MAR 28
PY 2013
VL 8
IS 3
AR e60374
DI 10.1371/journal.pone.0060374
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 121RP
UT WOS:000317262200111
PM 23555961
ER
PT J
AU Kulkarni, V
Rosati, M
Valentin, A
Ganneru, B
Singh, AK
Yan, J
Rolland, M
Alicea, C
Beach, RK
Zhang, GM
Le Gall, S
Broderick, KE
Sardesai, NY
Heckerman, D
Mothe, B
Brander, C
Weiner, DB
Mullins, JI
Pavlakis, GN
Felber, BK
AF Kulkarni, Viraj
Rosati, Margherita
Valentin, Antonio
Ganneru, Brunda
Singh, Ashish K.
Yan, Jian
Rolland, Morgane
Alicea, Candido
Beach, Rachel Kelly
Zhang, Gen-Mu
Le Gall, Sylvie
Broderick, Kate E.
Sardesai, Niranjan Y.
Heckerman, David
Mothe, Beatriz
Brander, Christian
Weiner, David B.
Mullins, James I.
Pavlakis, George N.
Felber, Barbara K.
TI HIV-1 p24(gag) Derived Conserved Element DNA Vaccine Increases the
Breadth of Immune Response in Mice
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; VIRAL REPLICATION
CAPACITY; LYMPHOCYTE RESPONSES; EPITOPE PRESENTATION; DISEASE
PROGRESSION; MEMBRANE PROTEIN-1; ESCAPE MUTATIONS; TYPE-1 PROTEINS;
RHESUS-MONKEYS
AB Viral diversity is considered a major impediment to the development of an effective HIV-1 vaccine. Despite this diversity, certain protein segments are nearly invariant across the known HIV-1 Group M sequences. We developed immunogens based on the highly conserved elements from the p24(gag) region according to two principles: the immunogen must (i) include strictly conserved elements of the virus that cannot mutate readily, and (ii) exclude both HIV regions capable of mutating without limiting virus viability, and also immunodominant epitopes located in variable regions. We engineered two HIV-1 p24(gag) DNA immunogens that express 7 highly Conserved Elements (CE) of 12-24 amino acids in length and differ by only 1 amino acid in each CE ('toggle site'), together covering >99% of the HIV-1 Group M sequences. Altering intracellular trafficking of the immunogens changed protein localization, stability, and also the nature of elicited immune responses. Immunization of C57BL/6 mice with p55(gag) DNA induced poor, CD4(+) mediated cellular responses, to only 2 of the 7 CE; in contrast, vaccination with p24CE DNA induced cross-clade reactive, robust T cell responses to 4 of the 7 CE. The responses were multifunctional and composed of both CD4(+) and CD8(+) T cells with mature cytotoxic phenotype. These findings provide a method to increase immune response to universally conserved Gag epitopes, using the p24CE immunogen. p24CE DNA vaccination induced humoral immune responses similar in magnitude to those induced by p55(gag), which recognize the virus encoded p24(gag) protein. The inclusion of DNA immunogens composed of conserved elements is a promising vaccine strategy to induce broader immunity by CD4(+) and CD8(+) T cells to additional regions of Gag compared to vaccination with p55(gag) DNA, achieving maximal cross-clade reactive cellular and humoral responses.
C1 [Kulkarni, Viraj; Alicea, Candido; Beach, Rachel Kelly; Zhang, Gen-Mu; Felber, Barbara K.] Frederick Natl Lab Canc Res, Human Retrovirus Pathogenesis Sect, Ctr Canc Res, Frederick, MD USA.
[Rosati, Margherita; Valentin, Antonio; Ganneru, Brunda; Singh, Ashish K.; Beach, Rachel Kelly; Zhang, Gen-Mu; Pavlakis, George N.] Frederick Natl Lab Canc Res, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD USA.
[Yan, Jian; Weiner, David B.] Univ Penn, Philadelphia, PA 19104 USA.
[Rolland, Morgane; Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
[Rolland, Morgane; Mullins, James I.] Univ Washington, Dept Med, Seattle, WA USA.
[Rolland, Morgane; Mullins, James I.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Le Gall, Sylvie] Ragon Inst MGH MIT & Harvard, Boston, MA USA.
[Broderick, Kate E.; Sardesai, Niranjan Y.] Inovio Pharmaceut Inc, Blue Bell, PA USA.
[Heckerman, David] Microsoft Res, Redmond, WA USA.
[Mothe, Beatriz; Brander, Christian] Autonomous Univ Barcelona, IrsiCaixa AIDS Res Inst HIVACAT, Barcelona, Spain.
[Brander, Christian] ICREA, Barcelona, Spain.
RP Pavlakis, GN (reprint author), Frederick Natl Lab Canc Res, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD USA.
EM pavlakig@mail.nih.gov; felberb@mail.nih.gov
RI Weiner, David/H-8579-2014; bebarta, vikhyat/K-3476-2015;
OI Brander, Christian/0000-0002-0548-5778
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health (NCI/NIH); Bill and Melinda Gates Foundation; Red
de Investigacion de Sida (RIS) [RD06/04]; Instituto de Salud Carlos III
(ISCIII), Madrid, Spain; Spanish FIPSE [36-0737-09]
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health (NCI/NIH). This
work was funded by Bill and Melinda Gates Foundation and was supported
in part by the Red de Investigacion de Sida (RIS) (RD06/04), Instituto
de Salud Carlos III (ISCIII), Madrid, Spain and the Spanish FIPSE
36-0737-09. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 76
TC 14
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 MAR 28
PY 2013
VL 8
IS 3
AR e60245
DI 10.1371/journal.pone.0060245
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 121RP
UT WOS:000317262200102
PM 23555935
ER
PT J
AU Miura, K
Diakite, M
Diouf, A
Doumbia, S
Konate, D
Keita, AS
Moretz, SE
Tullo, G
Zhou, H
Lopera-Mesa, TM
Anderson, JM
Fairhurst, RM
Long, CA
AF Miura, Kazutoyo
Diakite, Mahamadou
Diouf, Ababacar
Doumbia, Saibou
Konate, Drissa
Keita, Abdoul S.
Moretz, Samuel E.
Tullo, Gregory
Zhou, Hong
Lopera-Mesa, Tatiana M.
Anderson, Jennifer M.
Fairhurst, Rick M.
Long, Carole A.
TI Relationship between Malaria Incidence and IgG Levels to Plasmodium
falciparum Merozoite Antigens in Malian Children: Impact of Hemoglobins
S and C
SO PLOS ONE
LA English
DT Article
ID SICKLE-CELL TRAIT; APICAL MEMBRANE ANTIGEN-1; ANTIBODY-RESPONSES;
IMMUNE-RESPONSES; IMMUNOGLOBULIN-G; IN-VITRO; INFECTED ERYTHROCYTES;
ACQUIRED-IMMUNITY; SURFACE PROTEIN-1; VACCINE
AB Heterozygous hemoglobin (Hb) AS (sickle-cell trait) and HbAC are hypothesized to protect against Plasmodium falciparum malaria in part by enhancing naturally-acquired immunity to this disease. To investigate this hypothesis, we compared antibody levels to four merozoite antigens from the P. falciparum 3D7 clone (apical membrane antigen 1, AMA1-3D7; merozoite surface protein 1, MSP1-3D7; 175 kDa erythrocyte-binding antigen, EBA175-3D7; and merozoite surface protein 2, MSP2-3D7) in a cohort of 103 HbAA, 73 HbAS and 30 HbAC children aged 3 to 11 years in a malaria-endemic area of Mali. In the 2009 transmission season we found that HbAS, but not HbAC, significantly reduced the risk of malaria compared to HbAA. IgG levels to MSP1 and MSP2 at the start of this transmission season inversely correlated with malaria incidence after adjusting for age and Hb type. However, HbAS children had significantly lower IgG levels to EBA175 and MSP2 compared to HbAA children. On the other hand, HbAC children had similar IgG levels to all four antigens. The parasite growth-inhibitory activity of purified IgG samples did not differ significantly by Hb type. Changes in antigen-specific IgG levels during the 2009 transmission and 2010 dry seasons also did not differ by Hb type, and none of these IgG levels dropped significantly during the dry season. These data suggest that sickle-cell trait does not reduce the risk of malaria by enhancing the acquisition of IgG responses to merozoite antigens.
C1 [Miura, Kazutoyo; Diouf, Ababacar; Moretz, Samuel E.; Tullo, Gregory; Zhou, Hong; Lopera-Mesa, Tatiana M.; Anderson, Jennifer M.; Fairhurst, Rick M.; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Diakite, Mahamadou; Doumbia, Saibou; Konate, Drissa; Keita, Abdoul S.] Univ Bamako, Fac Med Pharm & Odontostomatol, Bamako, Mali.
RP Miura, K (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
EM kmiura@niaid.nih.gov; clong@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases/NIH; PATH/Malaria Vaccine Initiative
FX This study was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases/NIH. The GIA
Reference Center was supported by the PATH/Malaria Vaccine Initiative.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 48
TC 4
Z9 4
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 MAR 28
PY 2013
VL 8
IS 3
AR e60182
DI 10.1371/journal.pone.0060182
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 121RP
UT WOS:000317262200093
PM 23555917
ER
PT J
AU Shimada, M
Abe, S
Takahashi, T
Shiozaki, K
Okuda, M
Mizukami, H
Klinman, DM
Ozawa, K
Okuda, K
AF Shimada, Masaru
Abe, Shinya
Takahashi, Toru
Shiozaki, Kazumasa
Okuda, Mitsue
Mizukami, Hiroaki
Klinman, Dennis M.
Ozawa, Keiya
Okuda, Kenji
TI Prophylaxis and Treatment of Alzheimer's Disease by Delivery of an
Adeno-Associated Virus Encoding a Monoclonal Antibody Targeting the
Amyloid Beta Protein
SO PLOS ONE
LA English
DT Article
ID PHASE-I TRIAL; TRANSGENIC MICE; MOUSE MODEL; A-BETA(42) IMMUNIZATION;
IMMUNE-RESPONSE; MEMORY DEFICITS; SKELETAL-MUSCLE; BRAIN DELIVERY; GENE
DELIVERY; VIRAL VECTOR
AB We previously reported on a monoclonal antibody (mAb) that targeted amyloid beta (A beta) protein. Repeated injection of that mAb reduced the accumulation of A beta protein in the brain of human A beta transgenic mice (Tg2576). In the present study, cDNA encoding the heavy and light chains of this mAb were subcloned into an adeno-associated virus type 1 (AAV) vector with a 2A/furin adapter. A single intramuscular injection of 3.0x10(10) viral genome of these AAV vectors into C57BL/6 mice generated serum anti-A beta Ab levels up to 0.3 mg/ml. Anti-A beta Ab levels in excess of 0.1 mg/ml were maintained for up to 64 weeks. The effect of AAV administration on A beta levels in vivo was examined. A significant decrease in A beta levels in the brain of Tg2576 mice treated at 5 months (prophylactic) or 10 months (therapeutic) of age was observed. These results support the use of AAV vector encoding anti-A beta Ab for the prevention and treatment of Alzheimer's disease.
C1 [Shimada, Masaru; Abe, Shinya; Takahashi, Toru; Okuda, Kenji] Yokohama City Univ, Dept Mol Biodef Res, Yokohama, Kanagawa 232, Japan.
[Shiozaki, Kazumasa] Yokohama City Univ, Dept Psychiat, Yokohama, Kanagawa 232, Japan.
[Okuda, Mitsue] Okuda Dent Clin, Yokohama, Kanagawa, Japan.
[Mizukami, Hiroaki; Ozawa, Keiya] Jichi Med Sch, Ctr Mol Med, Div Genet Therapeut, Mibu, Tochigi, Japan.
[Klinman, Dennis M.] NCI, Expt Immunol Lab, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA.
RP Okuda, K (reprint author), Yokohama City Univ, Dept Mol Biodef Res, Yokohama, Kanagawa 232, Japan.
EM kokuda@chojuken.net
RI Mizukami, Hiroaki/D-7674-2013
OI Mizukami, Hiroaki/0000-0001-8954-874X
FU Ministry of Education, Science, Sports, Culture of Japan; Ministry of
Health and Welfare of Japan
FX This work was supported in part by a grant-in-aid for the Ministry of
Education, Science, Sports, Culture of Japan, and the Ministry of Health
and Welfare of Japan. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 51
TC 7
Z9 7
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 MAR 28
PY 2013
VL 8
IS 3
AR e57606
DI 10.1371/journal.pone.0057606
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 121RP
UT WOS:000317262200002
PM 23555563
ER
PT J
AU Harding, J
Roberts, RM
Mirochnitchenko, O
AF Harding, John
Roberts, R. Michael
Mirochnitchenko, Oleg
TI Large animal models for stem cell therapy
SO STEM CELL RESEARCH & THERAPY
LA English
DT Review
ID IN-UTERO TRANSPLANTATION; MPTP-TREATED MONKEYS; TYROSINE-HYDROXYLASE;
DOPAMINERGIC-NEURONS; ADIPOSE-TISSUE; PIGS; VIVO; XENOTRANSPLANTATION;
ENGRAFTMENT; DISEASE
AB The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for novel animal models to expand the range of current studies, most of which have been conducted in rodents. Extant models are providing important information but have limitations for a variety of disease categories and can have different size and physiology relative to humans. These differences can preclude the ability to reproduce the results of animal-based preclinical studies in human trials. Larger animal species, such as rabbits, dogs, pigs, sheep, goats, and non-human primates, are better predictors of responses in humans than are rodents, but in each case it will be necessary to choose the best model for a specific application. There is a wide spectrum of potential stem cell-based products that can be used for regenerative medicine, including embryonic and induced pluripotent stem cells, somatic stem cells, and differentiated cellular progeny. The state of knowledge and availability of these cells from large animals vary among species. In most cases, significant effort is required for establishing and characterizing cell lines, comparing behavior to human analogs, and testing potential applications. Stem cell-based therapies present significant safety challenges, which cannot be addressed by traditional procedures and require the development of new protocols and test systems, for which the rigorous use of larger animal species more closely resembling human behavior will be required. In this article, we discuss the current status and challenges of and several major directions for the future development of large animal models to facilitate advances in stem cell-based regenerative medicine.
C1 [Harding, John; Mirochnitchenko, Oleg] NIH, Div Comparat Medicine ORIP DPCPSI OD, Bethesda, MD 20892 USA.
[Roberts, R. Michael] Univ Missouri, CS Bond Life Sci Ctr 240B, Div Anim Sci, Columbia, MO 65211 USA.
RP Mirochnitchenko, O (reprint author), NIH, Div Comparat Medicine ORIP DPCPSI OD, 6701 Democracy Blvd,Suite 943-950, Bethesda, MD 20892 USA.
EM oleg.mirochnitchenko@nih.gov
FU National Institutes of Health [R01HD069979]
FX This work was supported by National Institutes of Health grant
R01HD069979 (RMR). The views and opinions expressed in this article do
not necessarily represent those of the National Institutes of Health.
NR 50
TC 29
Z9 30
U1 4
U2 34
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1757-6512
J9 STEM CELL RES THER
JI Stem Cell Res. Ther.
PD MAR 28
PY 2013
VL 4
AR 23
DI 10.1186/scrt171
PG 9
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 122OY
UT WOS:000317328600001
PM 23672797
ER
PT J
AU Vytal, KE
Cornwell, BR
Letkiewicz, AM
Arkin, NE
Grillon, C
AF Vytal, Katherine E.
Cornwell, Brian R.
Letkiewicz, Allison M.
Arkin, Nicole E.
Grillon, Christian
TI The complex interaction between anxiety and cognition: insight from
spatial and verbal working memory
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE anxiety; working memory; cognition; startle; electromyography;
performance
ID OBSESSIVE-COMPULSIVE DISORDER; REGIONAL BRAIN ACTIVITY; THREAT-EVOKED
ANXIETY; PANIC DISORDER; PREFRONTAL CORTEX; TASK-PERFORMANCE; NEGATIVE
EMOTION; FUNCTIONAL MRI; AMYGDALA; WORRY
AB Anxiety can be distracting, disruptive, and incapacitating. Despite problems with empirical replication of this phenomenon, one fruitful avenue of study has emerged from working memory (WM) experiments where a translational method of anxiety induction (risk of shock) has been shown to disrupt spatial and verbal WM performance. Performance declines when resources (e.g., spatial attention, executive function) devoted to goal-directed behaviors are consumed by anxiety. Importantly, it has been shown that anxiety-related impairments in verbal WM depend on task difficulty, suggesting that cognitive load may be an important consideration in the interaction between anxiety and cognition. Here we use both spatial and verbal WM paradigms to probe the effect of cognitive load on anxiety-induced WM impairment across task modality. Subjects performed a series of spatial and verbal n-back tasks of increasing difficulty (1, 2, and 3-back) while they were safe or at risk for shock. Startle reflex was used to probe anxiety. Results demonstrate that induced-anxiety differentially impacts verbal and spatial WM, such that low and medium-load verbal WM is more susceptible to anxiety-related disruption relative to high-load, and spatial WM is disrupted regardless of task difficulty. Anxiety impacts both verbal and spatial processes, as described by correlations between anxiety and performance impairment, albeit the effect on spatial WM is consistent across load. Demanding WM tasks may exert top-down control over higher-order cortical resources engaged by anxious apprehension, however high-load spatial WM may continue to experience additional competition from anxiety-related changes in spatial attention, resulting in impaired performance. By describing this disruption across task modalities, these findings inform current theories of emotion-cognition interactions and may facilitate development of clinical interventions that seek to target cognitive impairments associated with anxiety.
C1 [Vytal, Katherine E.; Letkiewicz, Allison M.; Arkin, Nicole E.; Grillon, Christian] NIMH, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
[Cornwell, Brian R.] Swinburne Univ Technol, Fac Life & Social Sci, Hawthorn, Vic 3122, Australia.
RP Vytal, KE (reprint author), NIMH, 15K North Dr, Bethesda, MD 20892 USA.
EM katye.vytal@nih.gov
FU National Institute of Mental Health
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health.
NR 64
TC 18
Z9 18
U1 8
U2 84
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD MAR 28
PY 2013
VL 7
AR 93
DI 10.3389/fnhum.2013.00093
PG 11
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA 114FN
UT WOS:000316726600001
PM 23542914
ER
PT J
AU Neres, J
Engelhart, CA
Drake, EJ
Wilson, DJ
Fu, P
Boshoff, HI
Barry, CE
Gulick, AM
Aldrich, CC
AF Neres, Joao
Engelhart, Curtis A.
Drake, Eric J.
Wilson, Daniel J.
Fu, Peng
Boshoff, Helena I.
Barry, Clifton E., III
Gulick, Andrew M.
Aldrich, Courtney C.
TI Non-Nucleoside Inhibitors of BasE, an Adenylating Enzyme in the
Siderophore Biosynthetic Pathway of the Opportunistic Pathogen
Acinetobacter baumannii
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID IRON ACQUISITION FUNCTIONS; MYCOBACTERIUM-TUBERCULOSIS; FLUORESCENCE
POLARIZATION; ASSEMBLY-LINE; ANTIBIOTICS; VIRULENCE; IDENTIFICATION;
INFECTIONS; RESISTANCE; GENES
AB Siderophores are small-molecule iron chelators produced by bacteria and other microorganisms for survival under iron limiting conditions such as found in a mammalian host. Siderophore biosynthesis is essential for the virulence of many important Gram-negative pathogens including Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. We performed high-throughput screening against BasE, which is involved in siderophore biosynthesis in A. baumannii, and identified 6-phenyl-1-(pyridin-4-ylmethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid 15. Herein we report the synthesis, biochemical, and microbiological evaluation of a systematic series of analogues of the HTS hit 15. Analogue 67 is the most potent analogue with a K-D of 2 nM against BasE. Structural characterization of the inhibitors with BasE reveals that they bind in a unique orientation in the active site, occupying all three substrate binding sites, and thus can be considered as multisubstrate inhibitors. These results provide a foundation for future studies aimed at increasing both enzyme potency and antibacterial activity.
C1 [Neres, Joao; Engelhart, Curtis A.; Wilson, Daniel J.; Fu, Peng; Aldrich, Courtney C.] Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN 55455 USA.
[Engelhart, Curtis A.] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA.
[Drake, Eric J.; Gulick, Andrew M.] SUNY Buffalo, Hauptman Woodward Inst, Buffalo, NY 14203 USA.
[Drake, Eric J.; Gulick, Andrew M.] SUNY Buffalo, Dept Biol Struct, Buffalo, NY 14203 USA.
[Boshoff, Helena I.; Barry, Clifton E., III] NIAID, TB Res Sect, Bethesda, MD 20892 USA.
RP Aldrich, CC (reprint author), Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN 55455 USA.
EM aldri015@umn.edu
RI Barry, III, Clifton/H-3839-2012; Neres, Joao/A-1241-2011
OI Neres, Joao/0000-0003-4488-2423
FU National Institutes of Health [AI070219, GM-068440]; Intramural Research
Program of the NIAID in the National Institutes of Health
FX This research was supported by grants from the National Institutes of
Health (Grant AI070219 to C.C.A. and Grant GM-068440 to A.M.G.) and the
Intramural Research Program of the NIAID in the National Institutes of
Health (to C.E.B.). We thank Dr. Michael Walters (Institute for
Therapeutics Discovery and Development, University of Minnesota) for
assistance with the parallel synthesis and Prof. David H. Sherman (Life
Sciences Institute, University of Michigan) for plasmids pUC18 and
pKC1139.
NR 65
TC 10
Z9 10
U1 0
U2 14
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 MAR 28
PY 2013
VL 56
IS 6
BP 2385
EP 2405
DI 10.1021/jm301709s
PG 21
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 118NM
UT WOS:000317032200018
PM 23437866
ER
PT J
AU Sassano, MF
Doak, AK
Roth, BL
Shoichet, BK
AF Sassano, Maria F.
Doak, Allison K.
Roth, Bryan L.
Shoichet, Brian K.
TI Colloidal Aggregation Causes Inhibition of G Protein-Coupled Receptors
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID HIGH-THROUGHPUT; PROMISCUOUS INHIBITORS; ORAL BIOAVAILABILITY; FALSE
POSITIVES; SMALL MOLECULES; IN-VITRO; IDENTIFICATION; ACTIVATION;
DISCOVERY; CELLS
AB Colloidal aggregation is the dominant mechanism for artifactual inhibition of soluble proteins, and controls against it are now widely deployed. Conversely, investigating this mechanism for membrane-bound receptors has proven difficult. Here we investigate the activity of four well-characterized aggregators against three G protein-coupled receptors (GPCRs) recognizing peptide and protein ligands. Each of the aggregators was active at micromolar concentrations against the three GPCRs in cell-based assays. This activity could be attenuated by either centrifugation of the inhibitor stock solution or by addition of Tween-80 detergent. In the absence of agonist, the aggregators acted as inverse agonists, consistent with a direct receptor interaction. Meanwhile, several literature GPCR ligands that resemble aggregators themselves formed colloids, by both physical and enzymological tests. These observations suggest that some GPCRs may be artifactually antagonized by colloidal aggregates, an effect that merits the attention of investigators in this field.
C1 [Sassano, Maria F.; Roth, Bryan L.] Univ North Carolina Chapel Hill Sch Med, Dept Pharmacol, Chapel Hill, NC 27759 USA.
[Sassano, Maria F.; Roth, Bryan L.] Univ North Carolina Chapel Hill Sch Med, NIMH Psychoact Drug Screening Program, Chapel Hill, NC 27759 USA.
[Doak, Allison K.; Shoichet, Brian K.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
RP Roth, BL (reprint author), Univ North Carolina Chapel Hill Sch Med, Dept Pharmacol, Chapel Hill, NC 27759 USA.
EM bryan_roth@med.unc.edu; bshoichet@gmail.com
RI sassano, maria/G-4941-2013; Roth, Bryan/F-3928-2010
FU NIH [GM71630]; Michael Hooker Chair of Protein Therapeutics and
Translational Proteomics, the NIMH Psychoactive Drug Screening Program
[U19MH82441]
FX Supported by NIH grants GM71630 (to BKS) and by the Michael Hooker Chair
of Protein Therapeutics and Translational Proteomics, the NIMH
Psychoactive Drug Screening Program and U19MH82441 (to BLR). We thank J.
Karpiak and R. Coleman for reading this manuscript and R. Coleman for
the Table of Contents graphic.
NR 52
TC 39
Z9 39
U1 1
U2 19
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD MAR 28
PY 2013
VL 56
IS 6
BP 2406
EP 2414
DI 10.1021/jm301749y
PG 9
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 118NM
UT WOS:000317032200019
PM 23437772
ER
PT J
AU Romagnoli, R
Baraldi, PG
Salvador, MK
Preti, D
Tabrizi, MA
Bassetto, M
Brancale, A
Hamel, E
Castagliuolo, I
Bortolozzi, R
Basso, G
Viola, G
AF Romagnoli, Romeo
Baraldi, Pier Giovanni
Salvador, Maria Kimatrai
Preti, Delia
Tabrizi, Mojgan Aghazadeh
Bassetto, Marcella
Brancale, Andrea
Hamel, Ernest
Castagliuolo, Ignazio
Bortolozzi, Roberta
Basso, Giuseppe
Viola, Giampietro
TI Synthesis and Biological Evaluation of
2-(Alkoxycarbonyl)-3-Anilinobenzo[b]thiophenes and
Thieno[2,3-b]pyridines as New Potent Anticancer Agents
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID TUBULIN-BINDING AGENTS; CELL-DEATH; MICROTUBULE INHIBITORS; ANTIMITOTIC
AGENTS; NATURAL-PRODUCTS; DRUG-RESISTANCE; APOPTOSIS; COLCHICINE;
CANCER; POLYMERIZATION
AB Two new series of inhibitors of tubulin polymerization based on the 2-(alkoxycarbonyl)-3-(3',4',5'-trimethoxyanilino)benzo[b]thiophene and thieno[2,3-b]pyridine molecular skeletons were synthesized and evaluated for antiproliferative activity on a panel of cancer cell lines, inhibition of tubulin polymerization, cell cycle effects, and in vivo potency. Antiproliferative activity was strongly dependent on the position of the methyl group on the benzene portion of the benzo[b]thiophene nucleus, with the greatest activity observed when the methyl was located at the C-6 position. Also, in the smaller thieno[2,3-b]pyridine series, the introduction of the methyl group at the C-6 position resulted in improvement of antiproliferative activity to the nanomolar level. The most active compounds (4i and 4n) did not induce cell death in normal human lymphocytes, suggesting that the compounds may be selective against cancer cells. Compound 4i significantly inhibited in vivo the growth of a syngeneic hepatocellular carcinoma in Balb/c mice.
C1 [Romagnoli, Romeo; Baraldi, Pier Giovanni; Salvador, Maria Kimatrai; Preti, Delia; Tabrizi, Mojgan Aghazadeh; Bassetto, Marcella; Brancale, Andrea] Univ Ferrara, Dipartimento Sci Farmaceut, I-44121 Ferrara, Italy.
[Romagnoli, Romeo; Baraldi, Pier Giovanni; Salvador, Maria Kimatrai; Preti, Delia; Tabrizi, Mojgan Aghazadeh; Bassetto, Marcella; Brancale, Andrea] Cardiff Univ, Sch Pharm & Pharmaceut Sci, Cardiff CF10 3NB, S Glam, Wales.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program,NIH, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA.
[Castagliuolo, Ignazio] Univ Padua, Dipartimento Med Mol, I-35121 Padua, Italy.
[Bortolozzi, Roberta; Basso, Giuseppe; Viola, Giampietro] Univ Padua, Dipartimento Salute Donna & Bambino, Lab Oncoematol, I-35128 Padua, Italy.
RP Romagnoli, R (reprint author), Univ Ferrara, Dipartimento Sci Farmaceut, I-44121 Ferrara, Italy.
EM rmr@unife.it; pgb@unife.it; giampietro.viola1@unipd.it
RI Romagnoli, Romeo/G-9887-2015; Baraldi, Pier Giovanni/B-7933-2017;
CASTAGLIUOLO, IGNAZIO/K-9963-2016; Viola, Giampietro/I-4095-2012;
Aghazadeh Tabrizi, Mojgan/I-9169-2014; Brancale, Andrea/N-9445-2014;
Bortolozzi, Roberta/D-4950-2015; preti, delia/G-9916-2015
OI CASTAGLIUOLO, IGNAZIO/0000-0001-9888-7030; Bassetto,
Marcella/0000-0002-2491-5868; BASSO, GIUSEPPE/0000-0002-2634-9302;
Viola, Giampietro/0000-0001-9329-165X; Brancale,
Andrea/0000-0002-9728-3419; Bortolozzi, Roberta/0000-0002-3357-4815;
preti, delia/0000-0002-1075-3781
FU Intramural NIH HHS [Z99 CA999999]
NR 60
TC 32
Z9 32
U1 3
U2 42
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD MAR 28
PY 2013
VL 56
IS 6
BP 2606
EP 2618
DI 10.1021/jm400043d
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 118NM
UT WOS:000317032200035
PM 23445496
ER
PT J
AU Kim, HJ
Kim, NC
Wang, YD
Scarborough, EA
Moore, J
Diaz, Z
MacLea, KS
Freibaum, B
Li, SQ
Molliex, A
Kanagaraj, AP
Carter, R
Boylan, KB
Wojtas, AM
Rademakers, R
Pinkus, JL
Greenberg, SA
Trojanowski, JQ
Traynor, BJ
Smith, BN
Topp, S
Gkazi, AS
Miller, J
Shaw, CE
Kottlors, M
Kirschner, J
Pestronk, A
Li, YR
Ford, AF
Gitler, AD
Benatar, M
King, OD
Kimonis, VE
Ross, ED
Weihl, CC
Shorter, J
Taylor, JP
AF Kim, Hong Joo
Kim, Nam Chul
Wang, Yong-Dong
Scarborough, Emily A.
Moore, Jennifer
Diaz, Zamia
MacLea, Kyle S.
Freibaum, Brian
Li, Songqing
Molliex, Amandine
Kanagaraj, Anderson P.
Carter, Robert
Boylan, Kevin B.
Wojtas, Aleksandra M.
Rademakers, Rosa
Pinkus, Jack L.
Greenberg, Steven A.
Trojanowski, John Q.
Traynor, Bryan J.
Smith, Bradley N.
Topp, Simon
Gkazi, Athina-Soragia
Miller, Jack
Shaw, Christopher E.
Kottlors, Michael
Kirschner, Janbernd
Pestronk, Alan
Li, Yun R.
Ford, Alice Flynn
Gitler, Aaron D.
Benatar, Michael
King, Oliver D.
Kimonis, Virginia E.
Ross, Eric D.
Weihl, Conrad C.
Shorter, James
Taylor, J. Paul
TI Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause
multisystem proteinopathy and ALS
SO NATURE
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; RNA-BINDING PROTEINS; DROSOPHILA MODEL;
SACCHAROMYCES-CEREVISIAE; FRONTOTEMPORAL DEMENTIA; MULTIPLE ALIGNMENT;
STRESS GRANULES; VCP MUTATIONS; TDP-43; DISEASE
AB Algorithms designed to identify canonical yeast prions predict that around 250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbour a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here we define pathogenic mutations in PrLDs of heterogeneous nuclear ribonucleoproteins (hnRNPs) A2B1 and A1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and in one case of familial amyotrophic lateral sclerosis. Wild-type hnRNPA2 (the most abundant isoform of hnRNPA2B1) and hnRNPA1 show an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a 'steric zipper' motif in the PrLD, which accelerates the formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Notably, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant steric zipper motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs should therefore be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone.
C1 [Kim, Hong Joo; Kim, Nam Chul; Moore, Jennifer; Freibaum, Brian; Li, Songqing; Molliex, Amandine; Kanagaraj, Anderson P.; Taylor, J. Paul] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38120 USA.
[Wang, Yong-Dong] St Jude Childrens Res Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38120 USA.
[Scarborough, Emily A.; Diaz, Zamia; Ford, Alice Flynn; Shorter, James] Univ Penn, Dept Biochem & Biophys, Perelman Sch Med, Philadelphia, PA 19104 USA.
[MacLea, Kyle S.; Ross, Eric D.] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA.
[Carter, Robert] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38120 USA.
[Boylan, Kevin B.; Wojtas, Aleksandra M.; Rademakers, Rosa] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.
[Pinkus, Jack L.; Greenberg, Steven A.] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA.
[Trojanowski, John Q.; Smith, Bradley N.] Univ Penn, Dept Pathol & Lab Med, Inst Aging, Philadelphia, PA 19104 USA.
[Trojanowski, John Q.; Smith, Bradley N.] Univ Penn, Ctr Neurodegenerat Dis Res, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Traynor, Bryan J.] NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Topp, Simon; Gkazi, Athina-Soragia; Miller, Jack; Shaw, Christopher E.] Kings Coll London, Ctr Neurodegenerat Res, Dept Clin Neurosci, Inst Psychiat, London SE5 8AF, England.
[Kottlors, Michael; Kirschner, Janbernd] Univ Childrens Hosp Freiburg, Div Neuropediat & Muscle Disorders, D-79106 Freiburg, Germany.
[Pestronk, Alan; Weihl, Conrad C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Li, Yun R.] Univ Penn, Med Sci Training Program, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Gitler, Aaron D.] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
[Benatar, Michael] Univ Miami, Neurol Dept, Miller Sch Med, Miami, FL 33136 USA.
[King, Oliver D.] Boston Biomed Res Inst, Watertown, MA 02472 USA.
[Kimonis, Virginia E.] Univ Calif Irvine, Dept Pediat, Div Genet & Metab, Irvine, CA 92696 USA.
RP Taylor, JP (reprint author), St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38120 USA.
EM jshorter@mail.med.upenn.edu; JPaul.Taylor@STJUDE.ORG
RI Traynor, Bryan/G-5690-2010; Smith, Bradley/H-6107-2013; Wang,
Yong-Dong/K-3563-2013; Kirschner, Janbernd/H-7418-2016;
OI Kirschner, Janbernd/0000-0003-1618-7386; topp,
simon/0000-0002-5200-3284; Ross, Eric/0000-0002-6473-9977
FU ALSAC; Packard Foundation; National Institutes of Health (NIH)
[NS053825]; ALS Association; NIH [AG032953, DP2OD002177, NS067354,
AG031867]; Ellison Medical Foundation; National Science Foundation
[MCB-1023771]
FX We thank the patients whose participation made this work possible. We
thank the St Jude Pediatric Cancer Genome Project and J. Zhang in
particular for providing access to control sequencing data. We thank C.
Gellera, B. Baloh, M. Harms, S. Krause, G. Dreyfuss and T. Cundy for
sharing reagents. We thank S. Donkervoort and S. Mumm for coordinating
samples, and A. Taylor for editorial assistance. J.P.T. was supported by
ALSAC, the Packard Foundation and the National Institutes of Health
(NIH) (NS053825); J.P.T. and M. B. were supported by the ALS
Association; J.Q.T. was supported by the NIH (AG032953); J.S. was
supported by the NIH (DP2OD002177 and NS067354) and the Ellison Medical
Foundation; E. D. R. was supported by the National Science Foundation
(MCB-1023771). C. C. W. was supported by the NIH (AG031867).
NR 37
TC 320
Z9 329
U1 106
U2 204
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD MAR 28
PY 2013
VL 495
IS 7442
BP 467
EP +
DI 10.1038/nature11922
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800037
PM 23455423
ER
PT J
AU Lurie, N
Manolio, T
Patterson, AP
Collins, F
Frieden, T
AF Lurie, Nicole
Manolio, Teri
Patterson, Amy P.
Collins, Francis
Frieden, Thomas
TI Research as a Part of Public Health Emergency Response
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Lurie, Nicole] Dept Hlth & Human Serv, Off Assistant Secretary Preparedness & Response, Washington, DC USA.
[Manolio, Teri; Patterson, Amy P.; Collins, Francis] NIH, Bethesda, MD 20892 USA.
[Frieden, Thomas] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Lurie, N (reprint author), Dept Hlth & Human Serv, Off Assistant Secretary Preparedness & Response, Washington, DC USA.
NR 4
TC 44
Z9 44
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
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 28
PY 2013
VL 368
IS 13
BP 1251
EP 1255
DI 10.1056/NEJMsb1209510
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 116FU
UT WOS:000316869000017
PM 23534565
ER
PT J
AU Palumbo, T
Faucz, FR
Azevedo, M
Xekouki, P
Iliopoulos, D
Stratakis, CA
AF Palumbo, T.
Faucz, F. R.
Azevedo, M.
Xekouki, P.
Iliopoulos, D.
Stratakis, C. A.
TI Functional screen analysis reveals miR-26b and miR-128 as central
regulators of pituitary somatomammotrophic tumor growth through
activation of the PTEN-AKT pathway
SO ONCOGENE
LA English
DT Article
DE microRNAs; growth-hormone producing adenomas; Carney complex;
acromegaly; pituitary hyperplasia; protein kinase A
ID MCCUNE-ALBRIGHT-SYNDROME; CELL SELF-RENEWAL; CARNEY COMPLEX; MICRORNA
GENES; BREAST-CANCER; BMI-1; EXPRESSION; ADENOMAS; PROLIFERATION;
MUTATIONS
AB MicroRNAs (miRNAs) have been involved in the pathogenesis of different types of cancer; however, their function in pituitary tumorigenesis remains poorly understood. Cyclic-AMP-dependent protein kinase-defective pituitaries occasionally form aggressive growth-hormone (GH)-producing pituitary tumors in the background of hyperplasia caused by haploinsufficiency of the protein kinase's main regulatory subunit, PRKAR1A. The molecular basis for this development remains unknown. We have identified a 17-miRNA signature of pituitary tumors formed in the background of hyperplasia (caused in half of the cases by PRKAR1A-mutations). We selected two miRNAs on the basis of their functional screen analysis: inhibition of miR-26b expression and upregulation of miR-128 suppressed the colony formation ability and invasiveness of pituitary tumor cells. Furthermore, we identified that miR-26b and miR-128 affected pituitary tumor cell behavior through regulation of their direct targets, PTEN and BMI1, respectively. In addition, we found that miR-128 through BMI1 direct binding on the PTEN promoter affected PTEN expression levels and AKT activity in the pituitary tumor cells. Our in vivo data revealed that inhibition of miR-26b and overexpression of miR-128 could suppress pituitary GH3 tumor growth in xenografts. Taken together, we have identified a miRNA signature for GH-producing pituitary tumors and found that miR-26b and miR-128 regulate the activity of the PTEN-AKT pathway in these tumors. This is the first suggestion of the possible involvement of miRNAs regulating the PTEN-AKT pathway in GH-producing pituitary tumor formation in the context of hyperplasia or due to germline PRKAR1A defects. MiR-26b suppression and miR-128 upregulation could have therapeutic potential in GH-producing pituitary tumor patients. Oncogene (2013) 32, 1651-1659; doi: 10.1038/onc.2012.190; published online 21 May 2012
C1 [Palumbo, T.; Iliopoulos, D.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
[Palumbo, T.; Iliopoulos, D.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
[Faucz, F. R.; Azevedo, M.; Xekouki, P.; Stratakis, C. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, Bethesda, MD USA.
[Faucz, F. R.] Pontificia Univ Catolica Parana, Grp Adv Mol Invest, Grad Program Hlth Sci, Ctr Biol & Sci, Curitiba, Parana, Brazil.
RP Iliopoulos, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
EM Dimitrios_iliopoulos@dfci.harvard.edu; stratakc@mail.nih.gov
FU Intramural NIH HHS [ZIA HD008920-02]
NR 49
TC 45
Z9 52
U1 4
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAR 28
PY 2013
VL 32
IS 13
BP 1651
EP 1659
DI 10.1038/onc.2012.190
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 116AY
UT WOS:000316855800005
PM 22614013
ER
PT J
AU Cashion, A
Stanfill, A
Thomas, F
Xu, LJ
Suttee, T
Eason, J
Ensell, M
Homayouni, R
AF Cashion, Ann
Stanfill, Ansley
Thomas, Fridtjof
Xu, Lijing
Suttee, Thomas
Eason, James
Ensell, Mang
Homayouni, Ramin
TI Expression Levels of Obesity-Related Genes Are Associated with Weight
Change in Kidney Transplant Recipients
SO PLOS ONE
LA English
DT Article
ID SUBCUTANEOUS ADIPOSE-TISSUE; CARBOXYPEPTIDASE-E; APOLIPOPROTEIN-M;
METABOLIC SYNDROME; LEPTIN; GAIN; DOPAMINE; SAMPLES
AB Background:The aim of this study was to investigate the association of gene expression profiles in subcutaneous adipose tissue with weight change in kidney transplant recipients and to gain insights into the underlying mechanisms of weight gain.
Methodology/Principal Findings: A secondary data analysis was done on a subgroup (n=26) of existing clinical and gene expression data from a larger prospective longitudinal study examining factors contributing to weight gain in transplant recipients. Measurements taken included adipose tissue gene expression profiles at time of transplant, baseline and six-month weight, and demographic data. Using multivariate linear regression analysis controlled for race and gender, expression levels of 1553 genes were significantly (p<0.05) associated with weight change. Functional analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes classifications identified metabolic pathways that were enriched in this dataset. Furthermore, GeneIndexer literature mining analysis identified a subset of genes that are highly associated with obesity in the literature and Ingenuity pathway analysis revealed several significant gene networks associated with metabolism and endocrine function. Polymorphisms in several of these genes have previously been linked to obesity.
Conclusions/Significance: We have successfully identified a set of molecular pathways that taken together may provide insights into the mechanisms of weight gain in kidney transplant recipients. Future work will be done to determine how these pathways may contribute to weight gain.
C1 [Cashion, Ann; Stanfill, Ansley; Ensell, Mang] Univ Tennessee, Ctr Hlth Sci, Dept Acute & Chron Care, Coll Nursing, Memphis, TN 38163 USA.
[Cashion, Ann] NINR, NIH, Bethesda, MD 20892 USA.
[Thomas, Fridtjof] Univ Tennessee, Ctr Hlth Sci, Dept Biostat & Epidemiol, Memphis, TN 38163 USA.
[Xu, Lijing; Suttee, Thomas; Homayouni, Ramin] Univ Memphis, Dept Biol, Memphis, TN 38152 USA.
[Eason, James] Methodist Univ Hosp Transplant Inst, Memphis, TN USA.
[Eason, James] Univ Tennessee, Ctr Hlth Sci, Dept Surg, Transplant Div, Memphis, TN 38163 USA.
RP Cashion, A (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Acute & Chron Care, Coll Nursing, Memphis, TN 38163 USA.
EM ann.cashion@nih.gov
FU NIH-NINR [USPHS R01 009270, USPHS 009270-0352]
FX This work was supported by NIH-NINR USPHS R01 009270 and NIH-NINR USPHS
009270-0352 (ARRA Summer Research Supplement Funds). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 37
TC 10
Z9 10
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 MAR 27
PY 2013
VL 8
IS 3
AR e59962
DI 10.1371/journal.pone.0059962
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 124QO
UT WOS:000317480700075
PM 23544116
ER
PT J
AU Murgai, M
Thomas, J
Cherepanova, O
Delviks-Frankenberry, K
Deeble, P
Pathak, VK
Rekosh, D
Owens, G
AF Murgai, Meera
Thomas, James
Cherepanova, Olga
Delviks-Frankenberry, Krista
Deeble, Paul
Pathak, Vinay K.
Rekosh, David
Owens, Gary
TI Xenotropic MLV envelope proteins induce tumor cells to secrete factors
that promote the formation of immature blood vessels
SO RETROVIROLOGY
LA English
DT Article
ID MURINE LEUKEMIA-VIRUS; CHRONIC-FATIGUE-SYNDROME; PROSTATE-CANCER;
RETROVIRUS XMRV; HOST-RANGE; METASTASIS; GAMMARETROVIRUSES; ONCOGENESIS;
RECEPTOR; SAMPLES
AB Background: Xenotropic Murine leukemia virus-Related Virus (XMRV) is a gamma-retrovirus initially reported to be present within familial human prostate tumors and the blood of patients with chronic fatigue syndrome. Subsequent studies however were unable to replicate these findings, and there is now compelling evidence that the virus evolved through rare retroviral recombination events in human tumor cell lines established through murine xenograft experiments. There is also no direct evidence that XMRV infection has any functional effects that contribute to tumor pathogenesis.
Results: Herein we describe an additional xenotropic MLV, "B4rv", found in a cell line derived from xenograft experiments with the human prostate cancer LNCaP cell line. When injected subcutaneously in nude mice, LNCaP cells infected with XMRV or B4rv formed larger tumors that were highly hemorrhagic and displayed poor pericyte/smooth muscle cell (SMC) investment, markers of increased metastatic potential. Conditioned media derived from XMRV- or B4rv-infected LNCaPs, but not an amphotropic MLV control virus infected LNCaPs, profoundly decreased expression of marker genes in cultured SMC, consistent with inhibition of SMC differentiation/maturation. Similar effects were seen with a chimeric virus of the amphotropic MLV control virus containing the XMRV env gene, but not with an XMRV chimeric virus containing the amphotropic MLV env gene. UV-inactivated XMRV and pseudovirions that were pseudotyped with XMRV envelope protein also produce conditioned media that downregulated SMC marker gene expression in vitro.
Conclusions: Together these results indicate that xenotropic MLV envelope proteins are sufficient to induce the production of factors by tumor cells that suppress vascular SMC differentiation, providing evidence for a novel mechanism by which xenotropic MLVs might alter tumor pathogenesis by disrupting tumor vascular maturation. Although it is highly unlikely that either XMRV or B4Rv themselves infect humans and are pathogenic, the results suggest that xenograft approaches commonly used in the study of human cancer promote the evolution of novel retroviruses with pathogenic properties.
C1 [Murgai, Meera; Cherepanova, Olga; Owens, Gary] Univ Virginia, Sch Med Charlottesville, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA.
[Thomas, James] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Deeble, Paul] Mary Baldwin Coll, Dept Biol, Staunton, VA 24401 USA.
[Delviks-Frankenberry, Krista; Pathak, Vinay K.] Natl Canc Inst, Viral Mutat Sect, HIV Drug Resistance Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Rekosh, David] Univ Virginia, Myles H Thaler Ctr AIDS & Human Retrovirus Res, Charlottesville, VA 22908 USA.
[Rekosh, David] Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22908 USA.
RP Owens, G (reprint author), Univ Virginia, Sch Med Charlottesville, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA.
EM gko@virginia.edu
RI Delviks-Frankenberry, Krista/M-4822-2013
FU NIH [R01 HL057353, R01 HL098538, R01 HL087867]; American Heart
Association [11POST7760009]
FX We would like to thank Mary E. McCanna, Rupa S. Tripathi, Melissa Bevard
and Dr. Elizabeth Greene for their knowledge and technical expertise, Dr
Sarah J. Parsons for providing us with the C4 cell lines, Dr Kimberly
Kelly for providing a C4-2 B4 cell line, and Dr Alan Rein for providing
us with MoMLV-4070a. This work was supported by NIH grants R01 HL057353,
R01 HL098538, and R01 HL087867 (to GKO). Ms. Murgai is supported by the
American Heart Association Predoctoral Fellowship 11POST7760009.
NR 35
TC 3
Z9 3
U1 0
U2 7
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 MAR 27
PY 2013
VL 10
AR 34
DI 10.1186/1742-4690-10-34
PG 14
WC Virology
SC Virology
GA 163FU
UT WOS:000320322200001
PM 23537062
ER
PT J
AU Kumar, NP
Gopinath, V
Sridhar, R
Hanna, LE
Banurekha, VV
Jawahar, MS
Nutman, TB
Babu, S
AF Kumar, Nathella Pavan
Gopinath, Venugopal
Sridhar, Rathinam
Hanna, Luke E.
Banurekha, Vaithilingam V.
Jawahar, Mohideen S.
Nutman, Thomas B.
Babu, Subash
TI IL-10 Dependent Suppression of Type 1, Type 2 and Type 17 Cytokines in
Active Pulmonary Tuberculosis
SO PLOS ONE
LA English
DT Article
ID GROWTH-FACTOR-BETA; T-CELL RESPONSES; MYCOBACTERIUM-TUBERCULOSIS;
IMMUNE-RESPONSE; INTERFERON-GAMMA; INFECTION; IL-23; MACROPHAGES;
EXPRESSION; CONTRIBUTE
AB Background: Although Type 1 cytokine responses are considered protective in pulmonary tuberculosis (PTB), their role as well as those of Type 2, 17 and immunoregulatory cytokines in tuberculous lymphadenitis (TBL) and latent tuberculosis (LTB) have not been well studied.
Aim and Methods: To identify cytokine responses associated with pulmonary tuberculosis (TB), TB lymphadenitits and latent TB, we examined mycobacterial antigen-specific immune responses of PTB, TBL and LTB individuals. More specifically, we examined ESAT-6 and CFP-10 induced Type 1, Type 2 and Type 17 cytokine production and their regulation using multiplex ELISA.
Results:PTB individuals exhibited a significantly lower baseline as well as antigen-specific production of Type 1 (IFN gamma, TNF alpha and IL-2); Type 2 (IL-4) and Type 17 (IL-17A and IL-17F) cytokines in comparison to both TBL and LTB individuals. TBL individuals exhibited significantly lower antigen-specific IFN gamma responses alone in comparison to LTB individuals. Although, IL-10 levels were not significantly higher, neutralization of IL-10 during antigen stimulation resulted in significantly enhanced production of IFN gamma, IL-4 and IL-17A in PTB individuals, indicating that IL-10 mediates (at least partially) the suppression of cytokine responses in PTB.
Conclusion: Pulmonary TB is characterized by an IL-10 dependent antigen-specific suppression of Type 1, Type 2 and Type 17 cytokines, reflecting an important association of these cytokines in the pathogenesis of active TB.
C1 [Kumar, Nathella Pavan; Gopinath, Venugopal; Babu, Subash] NIH, Int Ctr Excellence Res, Chennai, Tamil Nadu, India.
[Kumar, Nathella Pavan; Gopinath, Venugopal; Hanna, Luke E.; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.] Natl Inst Res TB, Chennai, Tamil Nadu, India.
[Sridhar, Rathinam] Govt Stanley Med Hosp, Chennai, Tamil Nadu, India.
[Nutman, Thomas B.; Babu, Subash] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Babu, S (reprint author), NIH, Int Ctr Excellence Res, Chennai, Tamil Nadu, India.
EM sbabu@mail.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases (NIAID)
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases (NIAID). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 34
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 MAR 27
PY 2013
VL 8
IS 3
AR e59572
DI 10.1371/journal.pone.0059572
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 124QO
UT WOS:000317480700035
PM 23544075
ER
PT J
AU Lu, C
Liu, XG
Wan, PY
Yu, P
AF Lu, Chi
Liu, Xiaoguang
Wan, Pingyu
Yu, Ping
TI Thiourea-Assisted Phosphate Conversion Coating on Mild Steel and
Characterizations by Cathodic Polarization and Linear Polarization
SO INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
LA English
DT Article
ID ELECTROCHEMICAL IMPEDANCE SPECTROSCOPY; PHOSPHORIC-ACID SOLUTION;
CORROSION-INHIBITORS; HYDROCHLORIC-ACID; HYDROGEN-SULFIDE; IRON;
DERIVATIVES; DESICCATION; PERFORMANCE; STABILITY
AB Using highly acidic phosphating solutions that dissolve rust, brush-on phosphating for large-scale steel structures can reduce the cost of rust removal, without the need of a post-treatment rinse. In very low pH medium, the presence of thiourea helps the formation of high-quality conversion films. A hydrogen sulfide acceleration mechanism is proposed, based on cathodic polarization data and previous studies. The formed films are amorphous and contain high water content, therefore a rather long post-treatment desiccation period is required and supported by analyzing the linear polarization resistance values in a desiccation model.
C1 [Lu, Chi] Univ Kentucky, Dept Elect & Comp Engn, Lexington, KY 40506 USA.
[Lu, Chi; Liu, Xiaoguang; Wan, Pingyu] Beijing Univ Chem Technol, Coll Sci, Beijing 100029, Peoples R China.
[Yu, Ping] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
RP Lu, C (reprint author), Univ Kentucky, Dept Elect & Comp Engn, Lexington, KY 40506 USA.
EM chi_lu_uky@yahoo.com
FU Ministry of Chemical Industry of China
FX This work was supported in part by multiple funding sources from the
Ministry of Chemical Industry of China (a predecessor of China Petroleum
and Chemical Industry Federation). We appreciate the editorial
assistance of the NIH Fellows Editorial Board.
NR 69
TC 4
Z9 4
U1 1
U2 13
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0888-5885
J9 IND ENG CHEM RES
JI Ind. Eng. Chem. Res.
PD MAR 27
PY 2013
VL 52
IS 12
BP 4547
EP 4555
DI 10.1021/ie303204j
PG 9
WC Engineering, Chemical
SC Engineering
GA 118NH
UT WOS:000317031700021
ER
PT J
AU Hayward, JA
Tachedjian, M
Cui, J
Field, H
Holmes, EC
Wang, LF
Tachedjian, G
AF Hayward, Joshua A.
Tachedjian, Mary
Cui, Jie
Field, Hume
Holmes, Edward C.
Wang, Lin-Fa
Tachedjian, Gilda
TI Identification of diverse full-length endogenous betaretroviruses in
megabats and microbats
SO RETROVIROLOGY
LA English
DT Article
DE Retrovirus; Betaretrovirus; Endogenous; Evolution; Bats; Pteropus;
Myotis; Rhinolophus
ID MAMMARY-TUMOR VIRUS; JAAGSIEKTE SHEEP RETROVIRUS; PFIZER MONKEY VIRUS;
MURINE LEUKEMIA-VIRUS; NUCLEOTIDE-SEQUENCE; RESPONSIVE ELEMENT;
BREAST-CANCER; PROTEIN; BATS; GENOME
AB Background: Betaretroviruses infect a wide range of species including primates, rodents, ruminants, and marsupials. They exist in both endogenous and exogenous forms and are implicated in animal diseases such as lung cancer in sheep, and in human disease, with members of the human endogenous retrovirus-K (HERV-K) group of endogenous betaretroviruses (beta ERVs) associated with human cancers and autoimmune diseases. To improve our understanding of betaretroviruses in an evolutionarily distinct host species, we characterized beta ERVs present in the genomes and transcriptomes of mega- and microbats, which are an important reservoir of emerging viruses.
Results: A diverse range of full-length beta ERVs were discovered in mega- and microbat genomes and transcriptomes including the first identified intact endogenous retrovirus in a bat. Our analysis revealed that the genus Betaretrovirus can be divided into eight distinct sub-groups with evidence of cross-species transmission. Betaretroviruses are revealed to be a complex retrovirus group, within which one sub-group has evolved from complex to simple genomic organization through the acquisition of an env gene from the genus Gammaretrovirus. Molecular dating suggests that bats have contended with betaretroviral infections for over 30 million years.
Conclusions: Our study reveals that a diverse range of betaretroviruses have circulated in bats for most of their evolutionary history, and cluster with extant betaretroviruses of divergent mammalian lineages suggesting that their distribution may be largely unrestricted by host species barriers. The presence of beta ERVs with the ability to transcribe active viral elements in a major animal reservoir for viral pathogens has potential implications for public health.
C1 [Hayward, Joshua A.; Tachedjian, Gilda] Burnet Inst, Ctr Virol, Retroviral Biol & Antivirals Lab, Melbourne, Vic 3004, Australia.
[Hayward, Joshua A.; Tachedjian, Gilda] Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia.
[Tachedjian, Mary; Wang, Lin-Fa] CSIRO Anim Food & Hlth Sci, Australian Anim Hlth Lab, Geelong, Vic 3220, Australia.
[Cui, Jie; Holmes, Edward C.] Univ Sydney, Sch Biol Sci, Sydney Emerging Infect & Biosecur Inst, Sydney, NSW 2006, Australia.
[Cui, Jie; Holmes, Edward C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Field, Hume] Queensland Ctr Emerging Infect Dis, Dept Agr Fisheries & Forestry, Brisbane, Qld 4007, Australia.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Wang, Lin-Fa] Duke NUS Grad Med Sch, Emerging Infect Dis Program, Singapore, Singapore.
[Wang, Lin-Fa] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
[Tachedjian, Gilda] Monash Univ, Dept Med, Melbourne, Vic 3004, Australia.
RP Tachedjian, G (reprint author), Burnet Inst, Ctr Virol, Retroviral Biol & Antivirals Lab, Melbourne, Vic 3004, Australia.
EM gildat@burnet.edu.au
OI Tachedjian, Gilda/0000-0002-7733-7037; Cui, Jie/0000-0001-8176-9951;
Holmes, Edward/0000-0001-9596-3552
FU Burnet Institute; Perpetual Philanthropic Services; Australian
Postgraduate Award; Monash University; National Health and Medical
Research Council of Australia (NHMRC) [543105]; NHMRC; OCE Science
Leader award
FX We thank Gary Crameri, Carol de Jong and Craig Smith for the provision
of tissues from R. megaphyllus. This study was funded by the Burnet
Institute and Perpetual Philanthropic Services. JAH was supported by an
Australian Postgraduate Award, Monash University, GT was supported by
the National Health and Medical Research Council of Australia (NHMRC)
Senior Research Fellowship 543105, and ECH was supported by an NHMRC
Australia Fellowship. The work conducted at the Australian Animal Health
Laboratory was partially supported by an OCE Science Leader award to
L-FW. The authors gratefully acknowledge the contribution to this work
of the Victorian Operational Infrastructure Support Program received by
the Burnet Institute.
NR 71
TC 20
Z9 20
U1 2
U2 31
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 MAR 27
PY 2013
VL 10
AR 35
DI 10.1186/1742-4690-10-35
PG 19
WC Virology
SC Virology
GA 121FO
UT WOS:000317228500001
PM 23537098
ER
PT J
AU Lamas, GA
Goertz, C
Boineau, R
Mark, DB
Rozema, T
Nahin, RL
Lindblad, L
Lewis, EF
Drisko, J
Lee, KL
AF Lamas, Gervasio A.
Goertz, Christine
Boineau, Robin
Mark, Daniel B.
Rozema, Theodore
Nahin, Richard L.
Lindblad, Lauren
Lewis, Eldrin F.
Drisko, Jeanne
Lee, Kerry L.
CA TACT Investigators
TI Effect of Disodium EDTA Chelation Regimen on Cardiovascular Events in
Patients With Previous Myocardial Infarction The TACT Randomized Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; ISCHEMIC-HEART-DISEASE; INTERMITTENT
CLAUDICATION; ENDOTHELIAL FUNCTION; CLINICAL-TRIALS; DOUBLE-BLIND;
VITAMIN-C; THERAPY; ATHEROSCLEROSIS; PREVENTION
AB Importance Chelation therapy with disodium EDTA has been used for more than 50 years to treat atherosclerosis without proof of efficacy.
Objective To determine if an EDTA-based chelation regimen reduces cardiovascular events.
Design, Setting, and Participants Double-blind, placebo-controlled, 2 x 2 factorial randomized trial enrolling 1708 patients aged 50 years or older who had experienced a myocardial infarction (MI) at least 6 weeks prior and had serum creatinine levels of 2.0 mg/dL or less. Participants were recruited at 134 US and Canadian sites. Enrollment began in September 2003 and follow-up took place until October 2011 (median, 55 months). Two hundred eighty-nine patients (17% of total; n=115 in the EDTA group and n=174 in the placebo group) withdrew consent during the trial.
Interventions Patients were randomized to receive 40 infusions of a 500-mL chelation solution (3 g of disodium EDTA, 7 g of ascorbate, B vitamins, electrolytes, procaine, and heparin) (n=839) vs placebo (n=869) and an oral vitamin-mineral regimen vs an oral placebo. Infusions were administered weekly for 30 weeks, followed by 10 infusions 2 to 8 weeks apart. Fifteen percent discontinued infusions (n=38 [16%] in the chelation group and n=41 [15%] in the placebo group) because of adverse events.
Main Outcome Measures The prespecified primary end point was a composite of total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. This report describes the intention-to-treat comparison of EDTA chelation vs placebo. To account for multiple interim analyses, the significance threshold required at the final analysis was P=.036.
Results Qualifying previous MIs occurred a median of 4.6 years before enrollment. Median age was 65 years, 18% were female, 9% were nonwhite, and 31% were diabetic. The primary end point occurred in 222 (26%) of the chelation group and 261 (30%) of the placebo group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.99]; P=. 035). There was no effect on total mortality (chelation: 87 deaths [10%]; placebo, 93 deaths [11%]; HR, 0.93 [95% CI, 0.70-1.25]; P=. 64), but the study was not powered for this comparison. The effect of EDTA chelation on the components of the primary end point other than death was of similar magnitude as its overall effect (MI: chelation, 6%; placebo, 8%; HR, 0.77 [95% CI, 0.54-1.11]; stroke: chelation, 1.2%; placebo, 1.5%; HR, 0.77 [95% CI, 0.34-1.76]; coronary revascularization: chelation, 15%; placebo, 18%; HR, 0.81 [95% CI, 0.64-1.02]; hospitalization for angina: chelation, 1.6%; placebo, 2.1%; HR, 0.72 [95% CI, 0.35-1.47]). Sensitivity analyses examining the effect of patient dropout and treatment adherence did not alter the results.
Conclusions and Relevance Among stable patients with a history of MI, use of an intravenous chelation regimen with disodium EDTA, compared with placebo, modestly reduced the risk of adverse cardiovascular outcomes, many of which were revascularization procedures. These results provide evidence to guide further research but are not sufficient to support the routine use of chelation therapy for treatment of patients who have had an MI.
C1 [Lamas, Gervasio A.] Columbia Univ, Div Cardiol, Mt Sinai Med Ctr, Miami Beach, FL 33140 USA.
[Goertz, Christine] Palmer Ctr Chiropract Res, Davenport, IA USA.
[Boineau, Robin] NHLBI, Bethesda, MD 20892 USA.
[Nahin, Richard L.] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA.
[Mark, Daniel B.; Lindblad, Lauren; Lee, Kerry L.] Duke Clin Res Inst, Durham, NC USA.
[Rozema, Theodore] Biogenesis Med Ctr, Landrum, SC USA.
[Lewis, Eldrin F.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Lewis, Eldrin F.] Harvard Univ, Sch Med, Boston, MA USA.
[Drisko, Jeanne] Univ Kansas, Med Ctr, Kansas City, MO USA.
RP Lamas, GA (reprint author), Columbia Univ, Div Cardiol, Mt Sinai Med Ctr, 4300 Alton Rd, Miami Beach, FL 33140 USA.
EM gervasio.lamas@msmc.com
OI Nahin, Richard/0000-0002-3682-4816; Mark, Daniel/0000-0001-6340-8087
FU NCCAM [U01AT001156]; NHLBI [U01HL092607]
FX The NCCAM (grant U01AT001156) and the NHLBI (grant U01HL092607) provided
sole support for this study.
NR 38
TC 58
Z9 59
U1 2
U2 23
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 27
PY 2013
VL 309
IS 12
BP 1241
EP 1250
DI 10.1001/jama.2013.2107
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 112WO
UT WOS:000316625200024
PM 23532240
ER
PT J
AU Redfield, MM
Chen, HH
Borlaug, BA
Semigran, MJ
Lee, KL
Lewis, G
LeWinter, MM
Rouleau, JL
Bull, DA
Mann, DL
Deswal, A
Stevenson, LW
Givertz, MM
Ofili, EO
O'Connor, CM
Felker, GM
Goldsmith, SR
Bart, BA
McNulty, SE
Ibarra, JC
Lin, G
Oh, JK
Patel, MR
Kim, RJ
Tracy, RP
Velazquez, EJ
Anstrom, KJ
Hernandez, AF
Mascette, AM
Braunwald, E
AF Redfield, Margaret M.
Chen, Horng H.
Borlaug, Barry A.
Semigran, Marc J.
Lee, Kerry L.
Lewis, Gregory
LeWinter, Martin M.
Rouleau, Jean L.
Bull, David A.
Mann, Douglas L.
Deswal, Anita
Stevenson, Lynne W.
Givertz, Michael M.
Ofili, Elizabeth O.
O'Connor, Christopher M.
Felker, G. Michael
Goldsmith, Steven R.
Bart, Bradley A.
McNulty, Steven E.
Ibarra, Jenny C.
Lin, Grace
Oh, Jae K.
Patel, Manesh R.
Kim, Raymond J.
Tracy, Russell P.
Velazquez, Eric J.
Anstrom, Kevin J.
Hernandez, Adrian F.
Mascette, Alice M.
Braunwald, Eugene
CA RELAX Trial
TI Effect of Phosphodiesterase-5 Inhibition on Exercise Capacity and
Clinical Status in Heart Failure With Preserved Ejection Fraction A
Randomized Clinical Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID PULMONARY-HYPERTENSION; RIGHT VENTRICLE; OXYGEN-UPTAKE; SILDENAFIL;
DYSFUNCTION; PREVENTS; 1-YEAR; RATS; HEMODYNAMICS; ASSOCIATION
AB Importance Studies in experimental and human heart failure suggest that phosphodiesterase-5 inhibitors may enhance cardiovascular function and thus exercise capacity in heart failure with preserved ejection fraction (HFPEF).
Objective To determine the effect of the phosphodiesterase-5 inhibitor sildenafil compared with placebo on exercise capacity and clinical status in HFPEF.
Design Multicenter, double-blind, placebo-controlled, parallel-group, randomized clinical trial of 216 stable outpatients with HF, ejection fraction >= 50%, elevated N-terminal brain-type natriuretic peptide or elevated invasively measured filling pressures, and reduced exercise capacity. Participants were randomized from October 2008 through February 2012 at 26 centers in North America. Follow-up was through August 30, 2012.
Interventions Sildenafil (n=113) or placebo (n=103) administered orally at 20 mg, 3 times daily for 12 weeks, followed by 60 mg, 3 times daily for 12 weeks. Main Outcome Measures Primary end point was change in peak oxygen consumption after 24 weeks of therapy. Secondary end points included change in 6-minute walk distance and a hierarchical composite clinical status score (range, 1-n, a higher value indicates better status; expected value with no treatment effect, 95) based on time to death, time to cardiovascular or cardiorenal hospitalization, and change in quality of life for participants without cardiovascular or cardiorenal hospitalization at 24 weeks.
Results Median age was 69 years, and 48% of patients were women. At baseline, median peak oxygen consumption (11.7 mL/kg/min) and 6-minute walk distance (308 m) were reduced. The median E/e' (16), left atrial volume index (44 mL/m(2)), and pulmonary artery systolic pressure (41 mm Hg) were consistent with chronically elevated left ventricular filling pressures. At 24 weeks, median (IQR) changes in peak oxygen consumption (mL/kg/min) in patients who received placebo (-0.20 [IQR, -0.70 to 1.00]) or sildenafil (-0.20 [IQR, -1.70 to 1.11]) were not significantly different (P=.90) in analyses in which patients with missing week-24 data were excluded, and in sensitivity analysis based on intention to treat with multiple imputation for missing values (mean between-group difference, 0.01 mL/kg/min, [95% CI, -0.60 to 0.61]). The mean clinical status rank score was not significantly different at 24 weeks between placebo (95.8) and sildenafil (94.2) (P=.85). Changes in 6-minute walk distance at 24 weeks in patients who received placebo (15.0 m [IQR, -26.0 to 45.0]) or sildenafil (5.0 m [IQR, -37.0 to 55.0]; P=.92) were also not significantly different. Adverse events occurred in 78 placebo patients (76%) and 90 sildenafil patients (80%). Serious adverse events occurred in 16 placebo patients (16%) and 25 sildenafil patients (22%).
Conclusion and Relevance Among patients with HFPEF, phosphodiesterase-5 inhibition with administration of sildenafil for 24 weeks, compared with placebo, did not result in significant improvement in exercise capacity or clinical status.
Trial Registration clinicaltrials.gov Identifier: NCT00763867 JAMA. 2013; 309(12): 1268-1277 Published online March 11, 2013. doi: 10.1001/jama.2013.2024 www.jama.com
C1 [Redfield, Margaret M.; Chen, Horng H.; Borlaug, Barry A.; Lin, Grace; Oh, Jae K.] Mayo Clin, Dept Med, Rochester, MN 55905 USA.
[Semigran, Marc J.; Lewis, Gregory] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Lee, Kerry L.; Anstrom, Kevin J.] Duke Clin Res Inst, Dept Biostat & Bioinformat, Durham, NC USA.
[Velazquez, Eric J.; Hernandez, Adrian F.] Duke Clin Res Inst, Dept Med, Durham, NC USA.
[McNulty, Steven E.] Duke Clin Res Inst, Dept Stat, Durham, NC USA.
[Ibarra, Jenny C.] Duke Clin Res Inst, Dept Project Management, Durham, NC USA.
[LeWinter, Martin M.] Univ Vermont, Dept Med, Burlington, VT 05405 USA.
[Tracy, Russell P.] Univ Vermont, Dept Pathol & Biochem, Burlington, VT 05405 USA.
[Rouleau, Jean L.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada.
[Rouleau, Jean L.] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Bull, David A.] Univ Utah, Dept Surg, Salt Lake City, UT USA.
[Mann, Douglas L.] Barnes Jewish Hosp, Dept Med, St Louis, MO 63110 USA.
[Deswal, Anita] Michael E DeBakey VA Med Ctr, Dept Med, Houston, TX USA.
[Deswal, Anita] Baylor Coll Med, Houston, TX 77030 USA.
[Stevenson, Lynne W.; Givertz, Michael M.; Braunwald, Eugene] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Ofili, Elizabeth O.] Morehouse Sch Med, Dept Med, Atlanta, GA 30310 USA.
[O'Connor, Christopher M.; Felker, G. Michael; Patel, Manesh R.; Kim, Raymond J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Kim, Raymond J.] Duke Univ, Med Ctr, Duke Cardiovasc Magnet Resonance Ctr, Durham, NC USA.
Duke Heart Ctr, Durham, NC USA.
[Goldsmith, Steven R.; Bart, Bradley A.] Hennepin Cty Med Ctr, Dept Med, Minneapolis, MN 55415 USA.
[Mascette, Alice M.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Redfield, MM (reprint author), Mayo Clin, Div Cardiovasc Dis, 200 1st St SW,Guggenheim 9, Rochester, MN 55905 USA.
EM redfield.margaret@mayo.edu
RI Hernandez, Adrian F./A-7818-2016;
OI Hernandez, Adrian F./0000-0003-3387-9616; Mann, Douglas
/0000-0002-2516-0145
FU National Institutes of Health (NIH); Medscape; Medscape, Amgen;
GlaxoSmithKline; Atcor Medical and Gilead; National Heart, Lung, and
Blood Institute; National Institute on Minority Health and Health
Disparities; Roche Diagnostics; Amgen; Novartis; Ikaria; Acetlion
Pharma; Heartware; ResMed; Pozen; GE Healthcare; Johnson Johnson;
Gilead; Critical Diagnostics; BG Medicine; Otsuka; Astellas; Novella;
Novella, Cytokinetics; Capricor; Singulex; Bristol-Myers Squibb; Amylin;
National Heart, Lung, and Blood Institute [U10HL084904, U10HL084861,
U10HL084875, U10HL084877, U10HL084889, U10HL084890, U10HL084891,
U10HL084899, U10HL084907, U10HL084931]; National Center for Advancing
Translational Sciences [UL1TR000454]; National Institute on Minority
Health and Health Disparities [8 U54 MD007588]
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Dr Redfield reported receiving
financial support from the National Institutes of Health (NIH) and
royalties from Annexon. Dr Chen reported receiving funding for patents
that his institution has licensed to Nile Therapeutics and Annexon with
other patents pending at the US Patent and Trademark Office. He also
reported that he has royalties with Nile Therapeutics, Annexon, and Up
To Date. Dr Borlaug reported receiving consulting fees from Medscape,
Amgen, and GlaxoSmithKline and receiving financial support from Atcor
Medical and Gilead. Dr Semigran reported receiving financial support
from the NIH for participation in the Heart Failure Network and from
Bayer. Dr Lee reported receiving financial support from the NIH for
participation in the Heart Failure Network. Dr LeWinter reported
receiving financial support from the NIH for participation in the Heart
Failure Network. Dr Bull reported receiving financial support from the
NIH for participation in the Heart Failure Network. Dr Deswal reported
receiving financial support from the NIH for participation in the Heart
Failure Network. Dr Stevenson reported receiving financial support from
the NIH for participation in the Heart Failure Network. Dr Givertz
reported receiving financial support from the NIH for participation in
the Heart Failure Network. Dr Ofili reported receiving financial support
from the NIH, receiving consulting fees from Merck, Novartis, and Arbor
Pharmaceuticals and lecture fees from Arbor Pharmaceuticals. She is
currently employed by the Morehouse School of Medicine and has grants
pending from the National Heart, Lung, and Blood Institute and National
Institute on Minority Health and Health Disparities. DrO'Connor reported
receiving consulting fees from Roche Diagnostics, Amgen, Novartis,
Ikaria, Acetlion Pharma, Heartware, ResMed, Pozen, GE Healthcare,
Johnson & Johnson, Gilead, Critical Diagnostics, BG Medicine, Otsuka,
Astellas, Novella, Cytokinetics, and Capricor; holding stock options
with Neurotronik/Interventional Autonomics Corporation; editing American
College of Cardiology; and coowning Cardiology Consulting Associates. Dr
Felker reported receiving financial support from the NIH; consulting
fees from Novartis, Amgen, Trevena, Roche Diagnostics, Merck, Singulex,
and BG Medicine; and funding from Amgen, Otsuka, and Roche Diagnostics.
Dr Bart reported receiving financial support from the NIH for
participation in the Heart Failure Network. Ms Ibarra reported receiving
financial support from the NIH for participation in the Heart Failure
Network. Dr Oh received financial support from the NIH for the Echo Core
Lab. Dr Patel has received consulting fees from Genzyme, Baxter, Jensen,
and Bayer, and his financial institution receives financial support from
AstraZeneca, Johnson & Johnson, and Maquet. Dr Kim reported receiving
financial support from the NIH as the Heart Failure Network Data
Coordinating Center and MRI Core Lab, and funding for a patent with
Northwestern University. His institution has received a grant from
Siemens. Dr Tracy reported receiving financial support from the NIH for
participation in the Heart Failure Network, and consulting fees
fromMerck, Tibotec-Johnson & Johnson, and Abbott. He has also given
expert testimony about biomarkers in blood clotting and is the owner of
Haematologic Technologies. Dr Velazquez reported receiving financial
support from the NIH for participation in the Heart Failure Network.; Dr
Anstrom reported receiving financial support from the NIH for
participation in the Heart Failure Network. Dr Hernandez reported
receiving financial support from the NIH for participation in the Heart
Failure Network and consulting fees from AstraZeneca, Corthera, Janseen,
and Bristol-Myers Squibb. His institution has received funding from
Amylin, Johnson & Johnson, and Bristol-Myers Squibb. Dr Braunwald
reported receiving consulting fees from Merck, Daiichi Sankyo, Genzyme,
Amorcyte, Medicines Co, MC Communications, Ikaria, CardioRentis,
sanofiaventis; funding (or pending funding) from AstraZeneca, Johnson &
Johnson, Merck, sanofi-aventis, Daiichi Sankyo, GlaxoSmithKline,
Bristol-Myers Squibb, Beckman Coulter, Roche Diagnostics, and Pfizer;
compensation for lectures for Eli Lilly, Merck, CVRx (no compensation),
CV Therapeutics (now Gilead), Daiichi Sankyo, MC Communications,
Manarini International, Medscape, and Bayer; and payment for
devel-opment of educational presentations from MC Communications. No
other disclosures were reported.; This work was supported by grants
U10HL084904 (for the data coordinating center), and U10HL084861,
U10HL084875, U10HL084877, U10HL084889, U10HL084890, U10HL084891,
U10HL084899, U10HL084907, and U10HL084931 (for the clinical centers)
from the National Heart, Lung, and Blood Institute. This work is also
supported by grant UL1TR000454 from the National Center for Advancing
Translational Sciences and grant 8 U54 MD007588 from the National
Institute on Minority Health and Health Disparities. Pfizer provided
study drug (sildenafil and matched placebo).
NR 31
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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 MAR 27
PY 2013
VL 309
IS 12
BP 1268
EP 1277
DI 10.1001/jama.2013.2024
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 112WO
UT WOS:000316625200027
PM 23478662
ER
PT J
AU Pogorzala, LA
Mishra, SK
Hoon, MA
AF Pogorzala, Leah A.
Mishra, Santosh K.
Hoon, Mark A.
TI The Cellular Code for Mammalian Thermosensation
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CAPSAICIN RECEPTOR; VANILLOID RECEPTOR; TRPA1 CONTRIBUTES; PAIN PATHWAY;
COLD; NEURONS; MICE; CHANNEL; TRPM8; NOCICEPTORS
AB Mammalian somatosenory neurons respond to thermal stimuli and allow animals to reliably discriminate hot from cold and to select their preferred environments. Previously, we generated mice that are completely insensitive to temperatures from noxious cold to painful heat (-5 to 55 degrees C) by ablating several different classes of nociceptor early in development. In the present study, we have adopted a selective ablation strategy in adult mice to study this phenotype and have demonstrated that separate populations of molecularly defined neurons respond to hot and cold. TRPV1-expressing neurons are responsible for all behavioral responses to temperatures between 40 and 50 degrees C, whereas TRPM8 neurons are required for cold aversion. We also show that more extreme cold and heat activate additional populations of nociceptors, including cells expressing Mrgprd. Therefore, although eliminating Mrgprd neurons alone does not affect behavioral responses to temperature, when combined with ablation of TRPV1 or TRPM8 cells, it significantly decreases responses to extreme heat and cold, respectively. Ablation of TRPM8 neurons distorts responses to preferred temperatures, suggesting that the pleasant thermal sensation of warmth may in fact just reflect reduced aversive input from TRPM8 and TRPV1 neurons. As predicted by this hypothesis, mice lacking both classes of thermosensor exhibited neither aversive nor attractive responses to temperatures between 10 and 50 degrees C. Our results provide a simple cellular basis for mammalian thermosensation whereby two molecularly defined classes of sensory neurons detect and encode both attractive and aversive cues.
C1 [Pogorzala, Leah A.; Mishra, Santosh K.; Hoon, Mark A.] NIDCR, Mol Genet Unit, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA.
RP Hoon, MA (reprint author), NIDCR, Mol Genet Unit, Lab Sensory Biol, NIH, Bldg 49,Room 1A16,49 Convent Dr, Bethesda, MD 20892 USA.
EM mark.hoon@nih.gov
FU National Institute of Dental and Craniofacial Research (NIDCR)-National
Institutes of Health
FX This research was supported by the intramural research program of the
National Institute of Dental and Craniofacial Research (NIDCR)-National
Institutes of Health (M. A. H.). We thank Dr. David Anderson for
providing Mrgprd-DTR mice, Nick Ryba for encouragement and helpful
advice, and Drs. Minh Nguyen and Lars von Buchholtz and members of the
Molecular Genetics Unit for valuable suggestions. Transgenic mice were
generated by Andrew Cho in the NIDCR Core Facility.
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PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 27
PY 2013
VL 33
IS 13
BP 5533
EP 5541
DI 10.1523/JNEUROSCI.5788-12.2013
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 117JD
UT WOS:000316948600011
PM 23536068
ER
PT J
AU Korn, EL
McShane, LM
Freidlin, B
AF Korn, Edward L.
McShane, Lisa M.
Freidlin, Boris
TI Statistical Challenges in the Evaluation of Treatments for Small Patient
Populations
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Review
ID ARRHYTHMIA SUPPRESSION TRIAL; RANDOMIZED CLINICAL-TRIALS; HIGH-DOSE
CHEMOTHERAPY; GASTROINTESTINAL STROMAL TUMORS; EFFECTIVE SUBSEQUENT
THERAPIES; CHRONIC MYELOGENOUS LEUKEMIA; DATA-MONITORING COMMITTEES;
VENTRICULAR ASSIST DEVICE; GILFORD PROGERIA SYNDROME; CHRONIC
MYELOID-LEUKEMIA
AB The development of a new treatment typically involves evaluation of its efficacy in a large clinical trial in which patients are randomly assigned either the new treatment or the standard of care. Results from these large randomized clinical trials allow for a definitive and unbiased assessment of the clinical benefit of the new treatment over the standard one. For rare diseases or for small patient subgroups identified within the context of a common disease, it may not be possible to conduct a large randomized trial. In this Review, we discuss alternative clinical study designs and statistical challenges that arise when attempting to assure that study results yield robust conclusions about the safety and effectiveness of a new medical product.
C1 [Korn, Edward L.; McShane, Lisa M.; Freidlin, Boris] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP McShane, LM (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, MSC 9735, Bethesda, MD 20892 USA.
EM lm5h@nih.gov
NR 93
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U1 0
U2 7
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 MAR 27
PY 2013
VL 5
IS 178
AR 178sr3
DI 10.1126/scitranslmed.3004018
PG 14
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 115EL
UT WOS:000316795300006
PM 23536014
ER
PT J
AU Fa, S
Pogrmic-Majkic, K
Dakic, V
Kaisarevic, S
Hrubik, J
Andric, N
Stojilkovic, SS
Kovacevic, R
AF Fa, Svetlana
Pogrmic-Majkic, Kristina
Dakic, Vanja
Kaisarevic, Sonja
Hrubik, Jelena
Andric, Nebojsa
Stojilkovic, Stanko S.
Kovacevic, Radmila
TI Acute effects of hexabromocyclododecane on Leydig cell cyclic nucleotide
signaling and steroidogenesis in vitro
SO TOXICOLOGY LETTERS
LA English
DT Article
DE Endocrine disrupters; Hexabromocyclododecane; Leydig cell
steroidogenesis; cAMP-signalling; Mitochondrial membrane potential
ID BROMINATED FLAME RETARDANTS; ACUTE REGULATORY PROTEIN; RAT TESTICULAR
ANDROGENESIS; GENE-EXPRESSION; TESTOSTERONE PRODUCTION;
PERFLUORODECANOIC ACID; CHOLESTEROL TRANSPORT; INHIBITION; EXPOSURE;
ATRAZINE
AB Hexabromocyclododecane (HBCDD), an additive brominated flame retardant routinely added to various consumer products, was reported to have toxic effects upon biota, including endocrine disruption. In this study, the potential toxicity of HBCDD was tested in peripubertal rat Leydig cells in vitro during 6 h exposure. HBCDD inhibited human chorionic gonadotropin-and forskolin-supported cAMP accumulation and steroidogenesis. It also inhibited basal cAMP production, but elevated basal steroidogenesis. The expression of several cAMP-dependent genes, including steroidogenic acute regulatory protein, cholesterol side chain cleavage enzyme, and 3 beta-hydroxysteroid dehydrogenase, was also inhibited by HBCDD treatment. Nevertheless, this was not accompanied by a decrease in steroidogenic acute regulatory protein expression, as documented by western blot analysis, and activity of steroidogenic enzymes, as documented by unaffected steroidogenesis in the presence of permeable 22(R)-hydroxycholesterol. However, HBCDD caused significant decrease in mitochondrial membrane potential in untreated and human chorionic gonadotropin-treated cells. This indicates that HBCDD acute toxicity in Leydig cells reflects changes in mitochondrial membrane potential-dependent cAMP production and basal and cAMP-regulated cholesterol transport. This in turn facilitates basal but inhibits cAMP-dependent steroidogenesis. Acute effects of HBCDD treatment on transcription are also indicative of its sustained effects on Leydig cell function. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Fa, Svetlana; Pogrmic-Majkic, Kristina; Dakic, Vanja; Kaisarevic, Sonja; Hrubik, Jelena; Andric, Nebojsa; Kovacevic, Radmila] Univ Novi Sad, Fac Sci, Dept Biol & Ecol, Lab Ecotoxicol, Novi Sad 21000, Serbia.
[Stojilkovic, Stanko S.] NICHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Kovacevic, R (reprint author), Univ Novi Sad, Fac Sci, Dept Biol & Ecol, Dositej Obradovic Sq 2, Novi Sad 21000, Serbia.
EM radmila.kovacevic@dbe.uns.ac.rs
FU Ministry of Science, Republic of Serbia [173037]; Autonomic Province of
Vojvodina [2570]; Eunce Kennedy Shiver National Institute of Health and
Human Development
FX We are grateful to Drs. D. M. Stocco for providing StAR antiserum and G.
D. Niswender for the supply of testosterone and progesterone antiserums.
This work is supported by the Ministry of Science, Republic of Serbia
(grant no. 173037), by the Autonomic Province of Vojvodina (grant no.
2570) and a Eunce Kennedy Shiver National Institute of Health and Human
Development intramural grant.
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD MAR 27
PY 2013
VL 218
IS 1
BP 81
EP 90
DI 10.1016/j.toxlet.2013.01.009
PG 10
WC Toxicology
SC Toxicology
GA 095TK
UT WOS:000315357400012
PM 23347875
ER
PT J
AU Afshin, A
Abioye, AI
Ajala, ON
Nguyen, AB
See, KC
Mozaffarian, D
AF Afshin, Ashkan
Abioye, Ajibola I.
Ajala, Oluremi N.
Nguyen, Anh B.
See, Kay C.
Mozaffarian, Dariush
TI Effectiveness of Mass Media Campaigns for Improving Dietary Behaviors: A
Systematic Review and Meta-analysis
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Diet; Health education; Nutrition
C1 [Afshin, Ashkan; Abioye, Ajibola I.; Ajala, Oluremi N.; See, Kay C.; Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Nguyen, Anh B.] NCI, Bethesda, MD 20892 USA.
NR 0
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U1 2
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P087
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100226
ER
PT J
AU Agyemang, P
Ayers, C
Lian, M
Das, S
Hoehner, C
Leonard, T
Berrigan, D
Ballard-Barbash, R
Powell-Wiley, TM
AF Agyemang, Priscilla
Ayers, Colby
Lian, Min
Das, Sandeep
Hoehner, Christine
Leonard, Tammy
Berrigan, David
Ballard-Barbash, Rachel
Powell-Wiley, Tiffany M.
TI Neighborhood-Level Socioeconomic Deprivation Predicts Weight Gain in a
Multi-Ethnic Population: Longitudinal Data from the Dallas Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Social Determinants of Health; Health disparities; Longitudinal studies
C1 [Agyemang, Priscilla; Berrigan, David; Ballard-Barbash, Rachel; Powell-Wiley, Tiffany M.] NIH, Bethesda, MD 20892 USA.
[Ayers, Colby; Das, Sandeep] Univ Texas Southwestern Med Cntr, Dallas, TX USA.
[Lian, Min; Hoehner, Christine] Washington Univ, Sch Med, St Louis, MO USA.
[Leonard, Tammy] Univ Texas Dallas, Richardson, TX 75083 USA.
NR 0
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA MP88
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100135
ER
PT J
AU Allen, NB
Chan, C
Kiefe, C
Wei, GN
Person, S
Sidney, S
Bibbins-Domingo, K
Goff, D
AF Allen, Norrina B.
Chan, Cheeling
Kiefe, Catarina
Wei, Gina
Person, Sharina
Sidney, Steve
Bibbins-Domingo, Kirsten
Goff, David
TI Gender and Racial Disparities in Access to Health Care: The Coronary
Artery Risk in Young Adults (CARDIA) Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Health services research; Health disparities
C1 [Allen, Norrina B.; Chan, Cheeling] Northwestern Univ, Chicago, IL 60611 USA.
[Kiefe, Catarina; Person, Sharina] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Wei, Gina] NHLBI, Bethesda, MD 20892 USA.
[Sidney, Steve] Kaiser Permanente, Div Rsch, Oakland, CA USA.
[Bibbins-Domingo, Kirsten] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Goff, David] Colorado Sch Publ Hlth, Denver, CO USA.
NR 0
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U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P343
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100461
ER
PT J
AU Auer, R
Vittinghoff, E
Kiefe, C
Reis, JP
Rodondi, N
Khodneva, YA
Kertesz, SG
Cornuz, J
Pletcher, MJ
AF Auer, Reto
Vittinghoff, Eric
Kiefe, Catharina
Reis, Jared P.
Rodondi, Nicolas
Khodneva, Yulia A.
Kertesz, Stefan G.
Cornuz, Jacques
Pletcher, Mark J.
TI Smoking Cessation and Long-term Changes in Physical Activity Level: The
Coronary Artery Risk Development in Young Adults (CARDIA) Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Physical activity; Smoking; Longitudinal studies
C1 [Auer, Reto; Vittinghoff, Eric; Pletcher, Mark J.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Kiefe, Catharina] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA.
[Reis, Jared P.] NHLBI, Bethesda, MD 20892 USA.
[Rodondi, Nicolas] Univ Bern, Bern, Switzerland.
[Khodneva, Yulia A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Kertesz, Stefan G.] Birmingham VA Med Cntr, Birmingham, AL USA.
[Cornuz, Jacques] Univ Lausanne, Lausanne, Switzerland.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P142
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100279
ER
PT J
AU Azeem, A
Yeboah, J
Bertoni, A
Burke, G
Turkbey, E
Szklo, M
Herrington, D
AF Azeem, Amir
Yeboah, Joseph
Bertoni, Alain
Burke, Gregory
Turkbey, Evrim
Szklo, Moyses
Herrington, David
TI Association of Hemoglobin A1C with Cardiovascular Disease and All-Cause
Mortality in Individuals without Diabetes - The Multi-Ethnic Study of
Atherosclerosis
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Cardiovascular disease; Risk factors; Glucose
C1 [Azeem, Amir; Yeboah, Joseph; Bertoni, Alain; Burke, Gregory; Herrington, David] Wake Forest Sch Med, Winston Salem, NC USA.
[Turkbey, Evrim] NIH, Bethesda, MD 20892 USA.
[Szklo, Moyses] Johns Hopkins Univ, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P278
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100398
ER
PT J
AU Bidulescu, A
Liu, JN
Morris, AA
Vaccarino, V
Quyyumi, AA
Gibbons, GH
AF Bidulescu, Aurelian
Liu, Jinnan
Morris, Alanna A.
Vaccarino, Viola
Quyyumi, Arshed A.
Gibbons, Gary H.
TI Race and Gender Differences in the Association between Vitamin D and
Adiponectin and its Relationship with Body Mass Index: The Meta-Health
Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Obesity; Gender; Health disparities
C1 [Bidulescu, Aurelian; Liu, Jinnan] Morehouse Sch Med Cardio Rsrch, Atlanta, GA USA.
[Morris, Alanna A.; Vaccarino, Viola; Quyyumi, Arshed A.] Emory Univ, Atlanta, GA 30322 USA.
[Gibbons, Gary H.] NHLBI, NIH, Bethesda, MD 20892 USA.
RI Bidulescu, Aurelian/N-2617-2014
OI Bidulescu, Aurelian/0000-0001-8211-8309
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P284
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100404
ER
PT J
AU Carson, AP
Steffes, MW
Carr, IJ
Kim, Y
Gross, MD
Carnethon, MR
Reis, JP
Loria, CM
Jacobs, DR
Lewis, CE
AF Carson, April P.
Steffes, Michael W.
Carr, I. J.
Kim, Yongin
Gross, Myron D.
Carnethon, Mercedes R.
Reis, Jared P.
Loria, Catherine M.
Jacobs, David R.
Lewis, Cora E.
TI Hemoglobin A1c and Progression of Coronary Artery Calcification: The
Coronary Artery Risk Development in Young Adults (CARDIA) Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Calcification
C1 [Carson, April P.; Kim, Yongin; Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Steffes, Michael W.; Gross, Myron D.; Jacobs, David R.] Univ Minnesota, Minneapolis, MN USA.
[Carr, I. J.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Carnethon, Mercedes R.] Northwestern Univ, Chicago, IL 60611 USA.
[Reis, Jared P.; Loria, Catherine M.] NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P384
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100502
ER
PT J
AU Cartv, CL
Hindorff, LA
Buyske, S
Haessler, J
Fesinmeyer, MD
Carlson, CS
Rao, DC
Chakravarti, A
Fornage, M
North, KE
Kooperberg, C
Franceschini, N
AF Cartv, Cara L.
Hindorff, Lucia A.
Buyske, Steven
Haessler, Jeff
Fesinmeyer, Megan D.
Carlson, Chris S.
Rao, D. C.
Chakravarti, Aravinda
Fornage, Myriam
North, Kari E.
Kooperberg, Charles
Franceschini, Nora
CA Population Architecture Using
TI Investigation of Blood Pressure Genetic Loci in African Americans using
the Metabochip
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Blood pressure; Genomics
C1 [Cartv, Cara L.; Haessler, Jeff; Fesinmeyer, Megan D.; Carlson, Chris S.; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Hindorff, Lucia A.] NHGRI, Bethesda, MD 20892 USA.
[Buyske, Steven] Rutgers State Univ, Piscataway, NJ USA.
[Rao, D. C.] Washington Univ, St Louis, MO USA.
[Chakravarti, Aravinda] Johns Hopkins Univ, Baltimore, MD USA.
[Fornage, Myriam] Univ Texas Houston, Houston, TX USA.
[North, Kari E.; Franceschini, Nora] Univ N Carolina, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA MP60
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100108
ER
PT J
AU Caughey, M
Laura, L
Avery, C
Ni, HY
Astor, B
Matsushita, K
Wruck, L
Rosamond, W
AF Caughey, Melissa
Laura, Loehr
Avery, Christy
Ni, Hanyu
Astor, Brad
Matsushita, Kunihiro
Wruck, Lisa
Rosamond, Wayne
TI Prevalence and Outcomes of Anemia in Patients Hospitalized with Acute
Decompensated Heart Failure: The ARIC Study Community Surveillance
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Heart failure; Blood cells; Country level epidemiologic data
C1 [Caughey, Melissa; Laura, Loehr; Avery, Christy; Wruck, Lisa; Rosamond, Wayne] Univ N Carolina, Chapel Hill, NC USA.
[Ni, Hanyu] NHLBI, Bethesda, MD 20892 USA.
[Astor, Brad] Univ Wisconsin, Madison, WI USA.
[Matsushita, Kunihiro] Johns Hopkins, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P013
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100155
ER
PT J
AU Chuang, ML
Gona, P
Salton, CJ
Tsao, CW
Yeon, SB
O'Donnelll, CJ
Manning, WJ
AF Chuang, Michael L.
Gona, Philimon
Salton, Carol J.
Tsao, Connie W.
Yeon, Susan B.
O'Donnelll, Christopher J.
Manning, Warren J.
TI Association of Clinical Characteristics and Cardiopulmonary Risk Factors
with Aortic and Pulmonary Arterial Enlargement by Magnetic Resonance
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Aorta; Magnetic resonance imaging; Risk factors
C1 [Chuang, Michael L.; Gona, Philimon; Tsao, Connie W.; O'Donnelll, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Salton, Carol J.; Yeon, Susan B.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P388
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100506
ER
PT J
AU Cogswell, M
Wang, CY
Chen, TC
Pfeiffer, C
Elliott, P
Gillespie, C
Carriquiry, A
Sempos, C
Liu, K
Perrine, C
Swanson, C
Caldwell, K
Loria, C
AF Cogswell, Mary
Wang, Chia-Yih
Chen, Te-Ching
Pfeiffer, Christine
Elliott, Paul
Gillespie, Cathleen
Carriquiry, Alicia
Sempos, Christopher
Liu, Kiang
Perrine, Cria
Swanson, Christine
Caldwell, Kathleen
Loria, Catherine
TI Validity of Predictive Equations for 24-Hour Urine Sodium Excretion in
Young Black and Other Adults
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Sodium; Epidemiologic methods; Nutrition
C1 [Cogswell, Mary; Pfeiffer, Christine; Gillespie, Cathleen; Perrine, Cria; Caldwell, Kathleen] CDC, Atlanta, GA 30333 USA.
[Wang, Chia-Yih; Chen, Te-Ching] CDC, Hyattsville, MD USA.
[Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, London, England.
[Carriquiry, Alicia] Iowa State Univ, Ames, IA USA.
[Sempos, Christopher; Swanson, Christine; Loria, Catherine] NIH, Rockville, MD USA.
[Liu, Kiang] Northwestern Univ, Evanston, IL USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA MP78
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100125
ER
PT J
AU Defago, MD
Gu, DF
Hixson, JE
Shimmin, LC
Rice, TK
Gu, CC
Jaquish, CE
Liu, DP
He, J
Kelly, TN
AF Defago, Maria D.
Gu, Dongfeng
Hixson, James E.
Shimmin, Lawrence C.
Rice, Treva K.
Gu, Charles C.
Jaquish, Cashell E.
Liu, Depei
He, Jiang
Kelly, Tanika N.
TI Common Genetic Variants in the Endothelial System Predict Blood Pressure
Response to Sodium Intake: The GenSalt Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Sodium; Blood pressure; Genetics
C1 [Defago, Maria D.] Inst Efectividad Clin & Sanitaria, Buenos Aires, DF, Argentina.
[Gu, Dongfeng] Cardiovasc Inst, Beijing, Peoples R China.
[Gu, Dongfeng] Fuwai Hosp, Beijing, Peoples R China.
[Hixson, James E.; Shimmin, Lawrence C.] Univ Texas Houston, Houston, TX USA.
[Rice, Treva K.; Gu, Charles C.] Washington Univ, St Louis, MO USA.
[Jaquish, Cashell E.] NHLBI, Bethesda, MD 20892 USA.
[Liu, Depei] Chinese Acad Med Sci, Beijing 100730, Peoples R China.
[Liu, Depei] Peking Union Med Coll, Beijing 100021, Peoples R China.
[He, Jiang; Kelly, Tanika N.] Tulane Univ, New Orleans, LA 70118 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA MP68
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100116
ER
PT J
AU Djousse, L
Benkeser, D
Arnold, A
Kizer, J
Zieman, S
Tracy, R
Gottdiener, J
Mozaffarian, D
Siscovick, D
Mukamal, K
Ix, J
AF Djousse, Luc
Benkeser, David
Arnold, Alice
Kizer, Jorge
Zieman, Susan
Tracy, Russell
Gottdiener, John
Mozaffarian, Dariush
Siscovick, David
Mukamal, Kenneth
Ix, Joachim
TI Plasma Free Fatty Acids are Positively Associated with Incident Heart
Failure in the Cardiovascular Health Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Fatty acids; Nutrition; Heart failure
C1 [Djousse, Luc; Mozaffarian, Dariush] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Djousse, Luc] Harvard Univ, Sch Med, Boston Vet Affairs Healthcare Syst, Boston, MA USA.
[Benkeser, David; Arnold, Alice; Siscovick, David] Univ Washington, Seattle, WA 98195 USA.
[Kizer, Jorge] Weill Cornell Med Coll, New York, NY USA.
[Zieman, Susan] NIA, Bethesda, MD 20892 USA.
[Tracy, Russell] Univ Vermont, Colchester, VT USA.
[Gottdiener, John] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA.
[Mozaffarian, Dariush; Mukamal, Kenneth] Harvard Univ, Sch Med, Boston, MA USA.
[Mukamal, Kenneth] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Ix, Joachim] Vet Affairs San Diego Heathcare Syst, San Diego, CA USA.
[Ix, Joachim] Univ Calif San Diego, San Diego, CA 92103 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA MP02
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100054
ER
PT J
AU Dutton, G
Loria, C
Carnethon, M
Durant, N
Gordon-Larsen, P
Jacobs, D
Shikany, J
Reis, J
Sidney, S
Lewis, CE
AF Dutton, Gareth
Loria, Catherine
Carnethon, Mercedes
Durant, Nefertiti
Gordon-Larsen, Penny
Jacobs, David
Shikany, James
Reis, Jared
Sidney, Stephen
Lewis, Cora E.
TI Secular and Aging-Related Weight Gain Slows among US Adults: The CARDIA
Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Obesity; Racial/ethnic disparties
C1 [Dutton, Gareth; Durant, Nefertiti; Shikany, James; Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Loria, Catherine; Reis, Jared] NHLBI, Bethesda, MD 20892 USA.
[Carnethon, Mercedes] Northwestern Univ, Chicago, IL 60611 USA.
[Gordon-Larsen, Penny] Univ N Carolina, Chapel Hill, NC USA.
[Jacobs, David] Univ Minnesota, Minneapolis, MN USA.
[Sidney, Stephen] Kaiser Permanente, Oakland, CA USA.
NR 0
TC 0
Z9 0
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P021
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100162
ER
PT J
AU Franceschini, N
Buyske, S
Hindorff, LA
Kooperberg, C
Boerwinkle, E
AF Franceschini, Nora
Buyske, Steve
Hindorff, Lucia A.
Kooperberg, Charles
Boerwinkle, Eric
TI Association of Genetic Variants with Incident Coronary Heart Disease in
African Americans
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Coronary artery disease; Genetics
C1 [Franceschini, Nora] Univ N Carolina, Chapel Hill, NC USA.
[Buyske, Steve] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA.
[Hindorff, Lucia A.] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA.
[Kooperberg, Charles] Fred Hutchinson Canc Rsch Cntr Carolina, Seattle, WA USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA MP35
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100085
ER
PT J
AU Garg, V
Vedanthan, R
Islami, F
Pourshams, A
Poutschi, H
Khademi, H
Naemi, M
Malekshah, AFT
Jafari, E
Salahi, R
Kamangar, F
Pharoah, PD
Abnet, CC
Brennan, P
Dawsey, SM
Fuster, V
Boffetta, P
Malekzadeh, R
AF Garg, Vaani
Vedanthan, Rajesh
Islami, Farhad
Pourshams, Akram
Poutschi, Hossein
Khademi, Hooman
Naemi, Mohammad
Malekshah, Akbar Fazel-Tabar
Jafari, Elham
Salahi, Rasool
Kamangar, Farin
Pharoah, Paul D.
Abnet, Christian C.
Brennan, Paul
Dawsey, Sanford M.
Fuster, Valentin
Boffetta, Paolo
Malekzadeh, Reza
TI Associations between Anthropometric Indices and the Prevalence of Heart
Disease in Iran: The Golestan Cohort Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Heart disease; Obesity; International Issues
C1 [Garg, Vaani; Vedanthan, Rajesh; Islami, Farhad; Fuster, Valentin; Boffetta, Paolo] Mt Sinai Sch Med, New York, NY USA.
[Pourshams, Akram; Poutschi, Hossein; Khademi, Hooman; Malekshah, Akbar Fazel-Tabar; Jafari, Elham; Malekzadeh, Reza] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran.
[Naemi, Mohammad; Salahi, Rasool] Gorgan Univ Med Sci, Sch Med, Dept Internal Med, Gorgan, Iran.
[Kamangar, Farin] Morgan State Univ, Dept Publ Hlth Anal, Sch Community Hlth & Policy, Baltimore, MD 21239 USA.
[Pharoah, Paul D.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Pharoah, Paul D.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA.
[Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RI Abnet, Christian/C-4111-2015
OI Abnet, Christian/0000-0002-3008-7843
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P108
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100246
ER
PT J
AU Gibbs, BB
Reis, JP
Schelbert, EB
Sidney, S
Craft, LL
Lima, J
Lewis, CE
AF Gibbs, Bethany Barone
Reis, Jared P.
Schelbert, Erik B.
Sidney, Steve
Craft, Lynette L.
Lima, Joao
Lewis, Cora E.
TI Sedentary Screen Time is Associated with Higher Left Ventricular Mass
and Posterior Wall Thickness in the Coronary Artery Risk Development in
Young Adults (CARDIA) Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Physical activity; Echocardiography; Obesity
C1 [Gibbs, Bethany Barone; Schelbert, Erik B.] Univ Pittsburgh, Pittsburgh, PA USA.
[Reis, Jared P.] NHLBI, Bethesda, MD 20892 USA.
[Sidney, Steve] Kaiser Permanente, Oakland, CA USA.
[Craft, Lynette L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Lima, Joao] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA 055
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100047
ER
PT J
AU Joehanes, R
Ying, SX
Johnson, AD
O'Connor, GT
DeMeo, DL
O'Donnell, CJ
Munson, PJ
Levy, D
AF Joehanes, Roby
Ying, Sai-xia
Johnson, Andrew D.
O'Connor, George T.
DeMeo, Dawn L.
O'Donnell, Christopher J.
Munson, Peter J.
Levy, Daniel
TI Gene Expression Signatures of Tobacco Exposure
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Smoking; Gene expression; Genomncs
C1 [Joehanes, Roby; Ying, Sai-xia; Munson, Peter J.] NIH, Bethesda, MD 20892 USA.
[Johnson, Andrew D.; O'Donnell, Christopher J.; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[O'Connor, George T.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[DeMeo, Dawn L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RI Johnson, Andrew/G-6520-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA 053
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100045
ER
PT J
AU Justice, A
North, K
Loos, R
Vedantam, S
Day, F
Berndt, S
Gustafsson, S
Locke, A
Powell, C
Bratati, K
Croteau-Chonka, D
Winkler, T
Scherag, A
Barroso, I
Beckmann, J
Lindgren, C
Pers, T
Visscher, P
Willer, C
Yang, J
Mohlke, K
Hirschorn, J
Ingelsson, E
Boehnke, M
Speliotes, E
AF Justice, Anne
North, Kari
Loos, Ruth
Vedantam, Sailaja
Day, Felix
Berndt, Sonja
Gustafsson, Stefan
Locke, Adam
Powell, Corey
Bratati, Kahali
Croteau-Chonka, Damien
Winkler, Thomas
Scherag, Andre
Barroso, Ines
Beckmann, Jacqui
Lindgren, Cecilia
Pers, Tune
Visscher, Peter
Willer, Cristen
Yang, Jian
Mohlke, Karen
Hirschorn, Joel
Ingelsson, Erik
Boehnke, Michael
Speliotes, Elizabeth
TI Meta-analysis of Genetic Associations in up to 339,224 Individuals
Identify 66 New Loci for Bmi, Confirming a Neuronal Contribution to Body
Weight Regulation and Implicating Several Novel Pathways
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Genetics; Obesity; Genomics
C1 [Justice, Anne; North, Kari] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Loos, Ruth] Mt Sinai Sch Med, New York, NY USA.
[Vedantam, Sailaja] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Day, Felix] Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England.
[Berndt, Sonja] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Gustafsson, Stefan; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Locke, Adam; Willer, Cristen; Boehnke, Michael] Univ Michigan, Dept Biostat, Cntr Stat Genet, Ann Arbor, MI 48109 USA.
[Powell, Corey; Bratati, Kahali] Univ Michigan, Dept Internal Med Gastroenterol, Ann Arbor, MI 48109 USA.
[Croteau-Chonka, Damien; Mohlke, Karen] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Winkler, Thomas] Univ Regensburg, Inst Epidemiol & Prevent Med, Med Cntr, D-93053 Regensburg, Germany.
[Scherag, Andre] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany.
[Barroso, Ines] Wellcome Trust Sanger Inst, Hinxton, England.
[Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Rsch Labs, Cambridge CB2 2QQ, England.
[Beckmann, Jacqui] CHU Vaudois, Univ Hosp, Serv Med Genet, CH-1011 Lausanne, Switzerland.
[Beckmann, Jacqui] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Lindgren, Cecilia] Univ Oxford, Wellcome Trust Cntr Human Genet, Oxford, England.
[Pers, Tune] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Visscher, Peter; Yang, Jian] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld, Australia.
[Hirschorn, Joel] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Hirschorn, Joel] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Hirschorn, Joel] Childrens Hosp, Program Genom, Boston, MA 02115 USA.
[Hirschorn, Joel] Broad Inst, Metab Initiat, Boston, MA USA.
[Hirschorn, Joel] Broad Inst, Program Med & Populat Genet, Boston, MA USA.
[Hirschorn, Joel] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Speliotes, Elizabeth] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Speliotes, Elizabeth] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA 050
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100042
ER
PT J
AU Kaplan, R
Aviles-Santa, LM
Parrinello, CM
Castaneda, S
Hankinson, AL
Isasi, CR
Birnbaum-Weitzman, O
Kim, R
Daviglus, ML
Talavera, GA
Schneiderman, N
Cai, JW
AF Kaplan, Robert
Aviles-Santa, Larissa M.
Parrinello, Christina M.
Castaneda, Sheila
Hankinson, Arlene L.
Isasi, Carmen R.
Birnbaum-Weitzman, Orit
Kim, Ryung
Daviglus, Martha L.
Talavera, Gregory A.
Schneiderman, Neil
Cai, Jianwen
TI Severe Obesity is Associated with Dramatic Increase in Cardiovascular
Disease Risk Factor Prevalence: Hispanic Community Health Study/Study of
Latinos (HCHS/SOL)
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Obesity; Health disparities; Risk factors
C1 [Kaplan, Robert; Parrinello, Christina M.; Isasi, Carmen R.; Kim, Ryung] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Aviles-Santa, Larissa M.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Castaneda, Sheila; Talavera, Gregory A.] San Diego State Univ, San Diego, CA 92182 USA.
[Hankinson, Arlene L.; Daviglus, Martha L.] Northwestern Univ, Chicago, IL 60611 USA.
[Birnbaum-Weitzman, Orit; Schneiderman, Neil] Univ Miami, Miami, FL USA.
[Cai, Jianwen] UNC Publ Hlth, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P292
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100412
ER
PT J
AU Kershaw, KN
Hankinson, A
Lewis, CE
Liu, K
Loria, CM
Reis, JP
Carnethon, MR
AF Kershaw, Kiarri N.
Hankinson, Arlene
Lewis, Cora E.
Liu, Kiang
Loria, Catherine M.
Reis, Jared P.
Carnethon, Mercedes R.
TI Positive and Negative Aspects of Social Relationships are Differentially
Associated with Longitudinal Increases in Body Mass Index and Waist
Circumference: The Coronary Artery Risk Development in Young Adults
(CARDIA) Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Social Determinants of Health; Obesity; Stress
C1 [Kershaw, Kiarri N.; Hankinson, Arlene; Liu, Kiang; Carnethon, Mercedes R.] Northwestern Univ, Chicago, IL 60611 USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Loria, Catherine M.; Reis, Jared P.] NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P119
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100257
ER
PT J
AU Leon, BM
Miller, BV
Zalos, G
Chen, KY
Sumner, AE
Cannon, RO
AF Leon, Benjamin M.
Miller, Bernard V.
Zalos, Gloria
Chen, Kong Y.
Sumner, Anne E.
Cannon, Richard O.
TI Reduced Fat Mass and Improved Insulin Sensitivity in Overweight Black
Women after Completion of 6-month Worksite Weight Loss Program
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Obesity; Insulin; Health disparities
C1 [Leon, Benjamin M.; Miller, Bernard V.; Zalos, Gloria; Chen, Kong Y.; Sumner, Anne E.; Cannon, Richard O.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P297
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100417
ER
PT J
AU Liu, JK
Coady, S
Hickson, DA
Taylor, HA
Fox, CS
AF Liu, Jiankang
Coady, Sean
Hickson, DeMarc A.
Taylor, Herman A.
Fox, Caroline S.
TI Neck Circumference as a New Clinical Predictor of Incident Diabetes
Mellitus: Results from 9-Year Follow-Up of the Jackson Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Obesity; Diabetes mellitus
C1 [Liu, Jiankang; Hickson, DeMarc A.; Taylor, Herman A.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Coady, Sean; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Coady, Sean; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P431
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100548
ER
PT J
AU McMahon, GM
O'Seaghdha, CM
Hwang, SJ
Meigs, JB
Fox, CS
AF McMahon, Gearoid M.
O'Seaghdha, Conall M.
Hwang, Shih-Jen
Meigs, James B.
Fox, Caroline S.
TI The Association of the CUBN Polymorphism rs1801239 and the Association
of Albuminuria and Cardiovascular Disease in the Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Cardiovascular disease; Risk factors; Renal function
C1 [McMahon, Gearoid M.; O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[McMahon, Gearoid M.; O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] Cntr Populat Studies, Framingham, MA USA.
[Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P309
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100428
ER
PT J
AU McMahon, GM
Preis, SR
Hwang, SJ
Fox, CS
AF McMahon, Gearoid M.
Preis, Sarah R.
Hwang, Shih-Jen
Fox, Caroline S.
TI Long Term Risk-Factor Profiles for Chronic Kidney Disease in the
Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Longitudinal studies; Risk factors; Renal function
C1 [McMahon, Gearoid M.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[McMahon, Gearoid M.; Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[Preis, Sarah R.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA MP74
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100121
ER
PT J
AU Meyer, M
Teng, Y
Schneiderman, N
Llabre, M
Cowie, C
Carnethon, M
Kaplan, R
Giachello, A
Gallo, L
Loehr, L
Barnharts, J
Aviles-Santa, L
Heiss, G
AF Meyer, Michelle
Teng, Yanping
Schneiderman, Neil
Llabre, Maria
Cowie, Catherine
Carnethon, Mercedes
Kaplan, Robert
Giachello, Aida
Gallo, Linda
Loehr, Laura
Barnharts, Janice
Aviles-Santa, Larissa
Heiss, Gerardo
TI Diversity in Hispanic Background and Burden of Metabolic Syndrome
Abnormalities: A Report from the HCHS/SOL
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Metabolism; Cardiovascular disease; Racial/ethnic disparities
C1 [Meyer, Michelle; Teng, Yanping; Loehr, Laura; Heiss, Gerardo] Univ N Carolina, Chapel Hill, NC USA.
[Schneiderman, Neil; Llabre, Maria] Univ Miami, Coral Gables, FL 33124 USA.
[Cowie, Catherine] NIDDK, Bethesda, MD 20892 USA.
[Carnethon, Mercedes; Giachello, Aida] Northwestern Univ, Chicago, IL 60611 USA.
[Kaplan, Robert; Barnharts, Janice] Einstein Coll Med, Bronx, NY USA.
[Gallo, Linda] San Diego State Univ, San Diego, CA 92182 USA.
[Aviles-Santa, Larissa] NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P437
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100554
ER
PT J
AU Reis, JP
Launer, L
Terry, JG
Loria, CM
Sidney, S
Yaffe, K
Jacobs, DR
Whitlow, CT
Zhu, N
Carr, JJ
AF Reis, Jared P.
Launer, Lenore
Terry, James G.
Loria, Catherine M.
Sidney, Stephen
Yaffe, Kristine
Jacobs, David R.
Whitlow, Christopher T.
Zhu, Na
Carr, J. J.
TI Subclinical Atherosclerosis and Cognitive Functioning in Middle-Aged
Black and White Adults: The CARDIA Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Calcification; Aging
C1 [Reis, Jared P.; Loria, Catherine M.] NHLBI, Bethesda, MD 20892 USA.
[Launer, Lenore] NIA, Bethesda, MD 20892 USA.
[Terry, James G.; Whitlow, Christopher T.; Carr, J. J.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Sidney, Stephen] Kaiser Permanente, Oakland, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Jacobs, David R.; Zhu, Na] Univ Minnesota, Minneapolis, MN USA.
RI Carr, John/A-1938-2012
OI Carr, John/0000-0002-4398-8237
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P043
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100184
ER
PT J
AU Rodriguez, CJ
Swett, K
Agarwal, SK
Folsom, AR
Loehr, LR
Fox, ER
Ni, HY
Rosamond, WD
Chang, PP
AF Rodriguez, Carlos J.
Swett, Katrina
Agarwal, Sunil K.
Folsom, Aaron R.
Loehr, Laura R.
Fox, Ervin R.
Ni, Hanyu
Rosamond, Wayne D.
Chang, Patricia P.
TI Systolic Blood Pressure Control among Hypertensives and Incident Heart
Failure: The Atherosclerosis Risk in Communities Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Blood pressure; Heart failure; Hypertension
C1 [Rodriguez, Carlos J.; Swett, Katrina] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Agarwal, Sunil K.] Johns Hopkins Univ, Baltimore, MD USA.
[Folsom, Aaron R.] Univ Minnesota, Minneapolis, MN USA.
[Loehr, Laura R.; Rosamond, Wayne D.; Chang, Patricia P.] Univ N Carolina, Chapel Hill, NC USA.
[Fox, Ervin R.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Ni, Hanyu] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA MP73
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100120
ER
PT J
AU Rosenquist, KJ
Massaro, JM
Krieger, BE
Murabito, JM
Hoffmann, U
Fox, CS
AF Rosenquist, Klara J.
Massaro, Joseph M.
Krieger, Bernard E.
Murabito, Joanne M.
Hoffmann, Udo
Fox, Caroline S.
TI Fat Quality Estimated by Computed Tomography and Associations with
Incident Cardiovascular Disease and All Cause Mortality
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Obesity; Outcomes
C1 [Rosenquist, Klara J.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA.
[Rosenquist, Klara J.] Harvard Univ, Sch Med, Boston, MA USA.
[Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Krieger, Bernard E.; Murabito, Joanne M.] Boston Med Cntr, Gen Internal Med Sect, Boston, MA USA.
[Krieger, Bernard E.; Murabito, Joanne M.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] NHLBI, Div Intra Mural Rsch, Framingham, MA USA.
[Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA MP63
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100111
ER
PT J
AU Shay, CM
Colangelo, L
Carnethon, MR
Liu, K
Allen, NB
Lewis, CE
Reis, JP
Jacobs, DR
Terry, JG
Carr, JJ
AF Shay, Christina M.
Colangelo, Laura
Carnethon, Mercedes R.
Liu, Kiang
Allen, Norrina B.
Lewis, Cora E.
Reis, Jared P.
Jacobs, David R.
Terry, J. G.
Carr, J. J.
TI Trajectories of Maintaining Recommended Amounts of Physical Activity in
Young Adulthood and Associations with Abdominal Adiposity in Middle Age:
The Cardia Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Physical activity; Obesity Longitudinal studies
C1 [Shay, Christina M.] Univ Oklahoma, Hlth Sci Cntr, Oklahoma City, OK USA.
[Colangelo, Laura; Carnethon, Mercedes R.; Liu, Kiang; Allen, Norrina B.] Northwestern Univ, Chicago, IL 60611 USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Reis, Jared P.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Jacobs, David R.] Univ Minnesota, Minneapolis, MN USA.
[Terry, J. G.; Carr, J. J.] Wake Forest Univ, Winston Salem, NC 27109 USA.
RI Carr, John/A-1938-2012
OI Carr, John/0000-0002-4398-8237
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA 047
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100039
ER
PT J
AU Siddique, J
Colangelo, LA
Reis, JP
Spring, B
Moller, AC
Lloyd-Jones, D
Liu, K
AF Siddique, Juned
Colangelo, Laura A.
Reis, Jared P.
Spring, Bonnie
Moller, Arlen C.
Lloyd-Jones, Donald
Liu, Kiang
TI Behavior Patterns over 20 Years and their Relationship to Subclinical
Atherosclerosis
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Longitudinal studies; Risk factors; Subclinical atherosclerosis
C1 [Siddique, Juned; Colangelo, Laura A.; Spring, Bonnie; Lloyd-Jones, Donald; Liu, Kiang] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Reis, Jared P.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Moller, Arlen C.] IIT, Chicago, IL 60616 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P378
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100496
ER
PT J
AU Sidney, S
Liu, K
Levine, DA
Bibbins-Domingo, K
Nguyen-Huynh, MN
Lima, J
Reis, JP
Loria, C
Lewis, CE
AF Sidney, Stephen
Liu, Kiang
Levine, Deborah A.
Bibbins-Domingo, Kirsten
Nguyen-Huynh, Mai N.
Lima, Joao
Reis, Jared P.
Loria, Catherine
Lewis, Cora E.
TI 24-Year Risk of Stroke in the Coronary Artery Risk Development in Young
Adults (CARDIA) Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Racial/ethnic disparities; Stroke; Blood pressure
C1 [Sidney, Stephen; Nguyen-Huynh, Mai N.] Kaiser Permanente No Calif, Oakland, CA USA.
[Liu, Kiang] Northwestern Univ, Chicago, IL 60611 USA.
[Levine, Deborah A.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Bibbins-Domingo, Kirsten] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Lima, Joao] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Reis, Jared P.; Loria, Catherine] NHLBI, Bethesda, MD 20892 USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA MP51
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100100
ER
PT J
AU Terry, JG
Lovato, J
Shay, CM
Reis, I
Gidding, SS
Schreiner, PJ
Goff, DC
Jacobss, DR
Carr, JJ
AF Terry, James G.
Lovato, James
Shay, Christina M.
Reis, Iared
Gidding, Samuel S.
Schreiner, Pamela J.
Goff, David C.
Jacobss, David R.
Carr, J. J.
TI Skeletal Muscle Adipose Tissue is Associated with Coronary Artery
Calcification: The CARDIA Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Obesity; Subclinical atherosclerosis; Coronary vessels
C1 [Terry, James G.; Lovato, James; Carr, J. J.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
[Shay, Christina M.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Reis, Iared] NIH, Bethesda, MD 20892 USA.
[Gidding, Samuel S.] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Schreiner, Pamela J.; Jacobss, David R.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[Goff, David C.] Colorado Sch Publ Hlth, Aurora, CO USA.
RI Carr, John/A-1938-2012
OI Carr, John/0000-0002-4398-8237
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA MP66
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100114
ER
PT J
AU Tsao, CW
Pencina, K
Massaro, JM
Levy, D
Vasan, RS
Hoffmann, U
O'Donnell, CJ
Mitchell, GF
AF Tsao, Connie W.
Pencina, Karol
Massaro, Joseph M.
Levy, Daniel
Vasan, Ramachandran S.
Hoffmann, Udo
O'Donnell, Christopher J.
Mitchell, Gary F.
TI Relations of Subclinical Measures of Arterial Stiffness and Pulsatility
with Arterial Calcification in Men and Women
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Aortic diseases; Calcification; Subclinical atherosclerosis
C1 [Tsao, Connie W.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Tsao, Connie W.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Boston, MA USA.
[Tsao, Connie W.] Beth Israel Deaconess Med Ctr, Framingham, MA USA.
[Tsao, Connie W.; Levy, Daniel; Vasan, Ramachandran S.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Pencina, Karol; Massaro, Joseph M.; Vasan, Ramachandran S.] Boston Univ, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Framingham, MA USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Mitchell, Gary F.] Cardiovasc Engn Inc F, Norwood, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P381
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100499
ER
PT J
AU Weinberg, I
Gona, P
O'Donnell, CJ
Jaff, MR
Murabito, J
AF Weinberg, Ido
Gona, Philimon
O'Donnell, Christopher J.
Jaff, Michael R.
Murabito, Joanne
TI Inter-arm Blood Pressure Difference and Cardiovascular Disease Risk in
the Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Subclinical atherosclerosis; Cardiovascular disease; Risk factors
C1 [Weinberg, Ido; Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Gona, Philimon] Univ Massachusetts, Sch Med, Boston, MA 02125 USA.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Boston, MA USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Murabito, Joanne] Framingham Heart Dis Epidemiol Study, Boston, MA USA.
[Murabito, Joanne] Boston Univ, Sch Med, Boston, MA 02118 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P075
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100216
ER
PT J
AU Zhu, N
Jacobs, DR
Meyer, KA
He, K
Launer, LJ
Reis, JP
Yaffe, K
Sidney, S
Whitmer, R
Steffen, LM
AF Zhu, Na
Jacobs, David R.
Meyer, Kate A.
He, Ka
Launer, Lenore J.
Reis, Jared P.
Yaffe, Kristine
Sidney, Stephen
Whitmer, Rachel
Steffen, Lyn M.
TI Dietary Pattern is Associated with Better Cognitive Function: The CARDIA
Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Diet; Aging; Prevention
C1 [Zhu, Na; Jacobs, David R.; Steffen, Lyn M.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[Meyer, Kate A.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[He, Ka] Indiana Univ, Sch Publ Hlth, Bloomington, IN USA.
[Launer, Lenore J.] NIA, Bethesda, MD 20892 USA.
[Reis, Jared P.] NHLBI, Bethesda, MD 20892 USA.
[Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Sidney, Stephen; Whitmer, Rachel] Kaiser Permanente Div Rsch, Oakland, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P400
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100517
ER
PT J
AU Wang, HY
Ma, CA
Zhao, YG
Fan, XY
Zhou, Q
Edmonds, P
Uzel, G
Oliveira, JB
Orange, J
Jain, A
AF Wang, Hong-Ying
Ma, Chi A.
Zhao, Yongge
Fan, Xiying
Zhou, Qing
Edmonds, Pamela
Uzel, Gulbu
Oliveira, Joao Bosco
Orange, Jordan
Jain, Ashish
TI Antibody deficiency associated with an inherited autosomal dominant
mutation in TWEAK
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE apoptosis; B cell lymphopenia; cysteine mutation; heteromers
ID COMMON VARIABLE IMMUNODEFICIENCY; AUTOIMMUNE LYMPHOPROLIFERATIVE
SYNDROME; KAPPA-B PATHWAY; MOLECULAR-BASIS; CELL; RECEPTOR; APOPTOSIS;
APRIL; BAFF; TNF
AB Mutations in the TNF family of proteins have been associated with inherited forms of immune deficiency. Using an array-based sequencing assay, we identified an autosomal-dominant deficiency in TNF-like weak inducer of apoptosis (TWEAK; TNFSF12) in a kindred with recurrent infection and impaired antibody responses to protein and polysaccharide vaccines. This mutation occurs in the sixth exon of TWEAK and results in the amino acid substitution R145C within the conserved TNF-homology domain of the full-length protein. TWEAK mutant protein formed high molecular weight aggregates under nonreducing conditions, suggesting an increased propensity for intermolecular interactions. As a result, mutant TWEAK associated with B-cell-activating factor (BAFF) protein and down-regulated the BAFF-mediated activation of the noncanonical NF-kappa B pathway through inhibition of p100 processing to p52, resulting in inhibition of BAFF-dependent B-cell survival and proliferation. As BAFF mediates T-cell-independent isotype switching and B-cell survival, our data implicate TWEAK as a disease-susceptibility gene for a humoral immunodeficiency.
C1 [Wang, Hong-Ying; Ma, Chi A.; Zhao, Yongge; Fan, Xiying; Edmonds, Pamela; Jain, Ashish] NIAID, Host Def Lab, Bethesda, MD 20892 USA.
[Zhou, Qing] NHGRI, Inflammatory Dis Sect, Bethesda, MD 20892 USA.
[Uzel, Gulbu] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Oliveira, Joao Bosco] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Orange, Jordan] Univ Penn, Dept Pediat, Sch Med, Philadelphia, PA 19104 USA.
RP Jain, A (reprint author), NIAID, Host Def Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ajain@niaid.nih.gov
RI Yu, Xiaomin/I-6407-2016;
OI orange, jordan/0000-0001-7117-7725; Oliveira, Joao/0000-0001-9388-8173;
Fan, Xiying/0000-0003-3090-381X
FU NIH/NIAID
FX We thank the patients' families for their participation in this study;
Ron Hornung and Margaret Brown for immunologic evaluations; Mary Derry
for editoral assistance; and Ivona Aksentijevich, Linda Burkly, and
Warren Strober for helpful discussions. This research was supported by
the Intramural Research Program of the NIH/NIAID.
NR 35
TC 15
Z9 16
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 26
PY 2013
VL 110
IS 13
BP 5127
EP 5132
DI 10.1073/pnas.1221211110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131XN
UT WOS:000318031900060
PM 23493554
ER
PT J
AU Bukalo, O
Campanac, E
Hoffman, DA
Fields, RD
AF Bukalo, Olena
Campanac, Emilie
Hoffman, Dax A.
Fields, R. Douglas
TI Synaptic plasticity by antidromic firing during hippocampal network
oscillations
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE long-term depression; long-term potentiation; network plasticity;
excitability
ID LONG-TERM DEPRESSION; TIMING-DEPENDENT PLASTICITY; HIGH-FREQUENCY
OSCILLATIONS; WAVE-RIPPLE COMPLEXES; IN-VITRO; SLEEP HOMEOSTASIS;
ACTION-POTENTIALS; PYRAMIDAL CELLS; DOWN-REGULATION; MEMORY
AB Learning and other cognitive tasks require integrating new experiences into context. In contrast to sensory-evoked synaptic plasticity, comparatively little is known of how synaptic plasticity may be regulated by intrinsic activity in the brain, much of which can involve nonclassical modes of neuronal firing and integration. Coherent high-frequency oscillations of electrical activity in CA1 hippocampal neurons [sharp-wave ripple complexes (SPW-Rs)] functionally couple neurons into transient ensembles. These oscillations occur during slow-wave sleep or at rest. Neurons that participate in SPW-Rs are distinguished from adjacent nonparticipating neurons by firing action potentials that are initiated ectopically in the distal region of axons and propagate antidromically to the cell body. This activity is facilitated by GABA(A)-mediated depolarization of axons and electrotonic coupling. The possible effects of antidromic firing on synaptic strength are unknown. We find that facilitation of spontaneous SPW-Rs in hippocampal slices by increasing gap-junction coupling or by GABAA-mediated axon depolarization resulted in a reduction of synaptic strength, and electrical stimulation of axons evoked a widespread, long-lasting synaptic depression. Unlike other forms of synaptic plasticity, this synaptic depression is not dependent upon synaptic input or glutamate receptor activation, but rather requires L-type calcium channel activation and functional gap junctions. Synaptic stimulation delivered after antidromic firing, which was otherwise too weak to induce synaptic potentiation, triggered a long-lasting increase in synaptic strength. Rescaling synaptic weights in subsets of neurons firing antidromically during SPW-Rs might contribute to memory consolidation by sharpening specificity of subsequent synaptic input and promoting incorporation of novel information.
C1 [Bukalo, Olena; Fields, R. Douglas] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Nervous Syst Dev & Plast Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Campanac, Emilie; Hoffman, Dax A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurophysiol & Biophys Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Fields, RD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Nervous Syst Dev & Plast Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
EM fieldsd@mail.nih.gov
RI Hoffman, Dax/E-5155-2011
OI Hoffman, Dax/0000-0001-6999-2157
FU National Institute of Child Health and Human Development
FX We thank K. A. Pelkey, A. Dityatev, H. Wake, A. Morozov, and T. Coate
for critically reading the manuscript and National Institute of Child
Health and Human Development intramural funding for support.
NR 55
TC 15
Z9 15
U1 1
U2 18
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 MAR 26
PY 2013
VL 110
IS 13
BP 5175
EP 5180
DI 10.1073/pnas.1210735110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131XN
UT WOS:000318031900068
PM 23479613
ER
PT J
AU Miranda, P
Contreras, JE
Plested, AJR
Sigworth, FJ
Holmgren, M
Giraldez, T
AF Miranda, Pablo
Contreras, Jorge E.
Plested, Andrew J. R.
Sigworth, Fred J.
Holmgren, Miguel
Giraldez, Teresa
TI State-dependent FRET reports calcium- and voltage-dependent gating-ring
motions in BK channels
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE allosteric regulation; SLO1 channel; fluorescence
ID GREEN FLUORESCENT PROTEIN; K+ CHANNEL; POTASSIUM CHANNEL; CA2+-DEPENDENT
ACTIVATION; STRUCTURAL DYNAMICS; ENERGY-TRANSFER; CA2+ BINDING;
SENSITIVITY; DOMAIN; SITES
AB Large-conductance voltage-and calcium-dependent potassium channels (BK, "Big K+") are important controllers of cell excitability. In the BK channel, a large C-terminal intracellular region containing a "gating-ring" structure has been proposed to transduce Ca2+ binding into channel opening. Using patch-clamp fluorometry, we have investigated the calcium and voltage dependence of conformational changes of the gating-ring region of BK channels, while simultaneously monitoring channel conductance. Fluorescence resonance energy transfer (FRET) between fluorescent protein inserts indicates that Ca2+ binding produces structural changes of the gating ring that are much larger than those predicted by current X-ray crystal structures of isolated gating rings.
C1 [Miranda, Pablo; Giraldez, Teresa] Univ Hosp Nuestra Senora de Candelaria, Div Res, Tenerife 38010, Spain.
[Miranda, Pablo] Univ La Laguna, Dept Physiol, Tenerife 38071, Spain.
[Contreras, Jorge E.; Holmgren, Miguel] NINDS, NIH, Bethesda, MD 20892 USA.
[Plested, Andrew J. R.] Leibniz Inst Mol Pharmacol, D-13125 Berlin, Germany.
[Plested, Andrew J. R.] Charite, NeuroCure, D-10117 Berlin, Germany.
[Sigworth, Fred J.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA.
RP Giraldez, T (reprint author), Univ Hosp Nuestra Senora de Candelaria, Div Res, Tenerife 38010, Spain.
EM giraldez@ull.es
RI Giraldez, Teresa/G-8970-2015;
OI Giraldez, Teresa/0000-0002-4096-810X; Plested,
Andrew/0000-0001-6062-0832
FU Instituto de Salud Carlos III-Subdirectorate General for Evaluation and
Promotion of Research Grants [MS07/00034, PI09/00406, PI12/00428];
Spanish Ministry of Economy Grant Consolider-Ingenio [CSD 2008-0005];
European Regional Development Funds from the European Union; National
Institutes of Health (NIH)-National Institute of Neurological Disorders
and Stroke; Deutsche Forschungsgemeinschaft [EXC257]; NIH [NS21501]
FX We thank Diana Wesch for performing preliminary experiments at early
stages of the project, which were not included in this manuscript; Diego
Alvarez de la Rosa, Barbara Ehrlich, and Patricio Rojas for helpful
comments on the manuscript; Deepa Srikumar for technical assistance; and
Jie Zheng for providing the CFP24YFP tandem plasmid. This work was
funded by Instituto de Salud Carlos III-Subdirectorate General for
Evaluation and Promotion of Research Grants MS07/00034, PI09/00406, and
PI12/00428, and Spanish Ministry of Economy Grant Consolider-Ingenio CSD
2008-0005; and cofinanced by the European Regional Development Funds, "A
Way of Making Europe," from the European Union (to T.G). Additional
support was from the intramural section of the National Institutes of
Health (NIH)-National Institute of Neurological Disorders and Stroke
(M.H.), Deutsche Forschungsgemeinschaft Grant EXC257 (to A.J.R.P.), and
NIH Grant NS21501 (to F.J.S.).
NR 41
TC 17
Z9 18
U1 0
U2 16
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 MAR 26
PY 2013
VL 110
IS 13
BP 5217
EP 5222
DI 10.1073/pnas.1219611110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131XN
UT WOS:000318031900075
PM 23479636
ER
PT J
AU Sigurjonsdottir, K
Bjorgulfsson, TM
Aspelund, T
Eiriksdottir, G
Sigurdsson, S
Ingvarsson, T
Harris, TB
Launer, L
Gudnason, V
Jonsson, H
AF Sigurjonsdottir, Kristin
Bjorgulfsson, Thorir M.
Aspelund, Thor
Eiriksdottir, Gudny
Sigurdsson, Sigurdur
Ingvarsson, Thorvaldur
Harris, Tamara B.
Launer, Lenore
Gudnason, Vilmundur
Jonsson, Helgi
TI Type 3 finger length pattern is associated with total knee replacements
due to osteoarthritis but not with hip replacements or hand
osteoarthritis in the elderly: The AGES-Reykjavik study
SO BMC MUSCULOSKELETAL DISORDERS
LA English
DT Article
DE Osteoarthritis; Finger length ratio; Epidemiology
ID 4TH DIGIT RATIO; SEX-HORMONES; 2ND; 2D/4D; PREDICTOR; TESTOSTERONE;
PERFORMANCE; ABILITY; SUCCESS; INDEX
AB Background: Recent case-control studies have shown an association between type 3 finger length pattern (longer ring finger than index finger) and knee osteoarthritis. This large cross-sectional study tests the hypothesis that the type 3 pattern is associated with total joint replacements due to osteoarthritis in a large population based study.
Methods: Finger length ratios were assessed visually on 5170 hand photographs (2975 females, 2195 males, mean age 76). In this population-based multidisciplinary study of aging in Reykjavik, Iceland, the prevalence of osteoarthritis associated total knee replacements was 223(4.3%) and total hip replacements 316(6.1%). We then performed a binary logistic regression analysis for total knee replacements and total hip replacements, including finger length patterns, osteoarthritis at other sites and other variables with possible association to osteoarthritis such as age, BMI and bone mineral density of the spine.
Results: The prevalence of the type 3 pattern was 50% (43% in females, 58% in males). The regression analysis revealed an odds ratio for total knee replacements of 1.65 (1.24-2.2) p = 0.0007, in the type 3 finger pattern group, similar in both genders. This association was independent of the associations we have previously reported between total knee replacements and BMI and the presence of hand osteoarthritis. No association was seen between finger length patterns and total hip replacements.
Conclusion: Finger length patterns read from digital photographs in this large study confirm previous radiographic observations with significant associations between the type 3 pattern and total knee replacements but not total hip replacements in both genders in this elderly group.
C1 [Sigurjonsdottir, Kristin; Bjorgulfsson, Thorir M.; Aspelund, Thor; Gudnason, Vilmundur; Jonsson, Helgi] Univ Iceland, Reykjavik, Iceland.
[Aspelund, Thor; Eiriksdottir, Gudny; Sigurdsson, Sigurdur; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Ingvarsson, Thorvaldur] Akureyri Cent Hosp, Akureyri, Iceland.
[Harris, Tamara B.; Launer, Lenore] NIA, Bethesda, MD 20892 USA.
[Sigurjonsdottir, Kristin; Jonsson, Helgi] Landspitalinn Univ Hosp ICELAND, Reykjavik, Iceland.
RP Sigurjonsdottir, K (reprint author), Univ Iceland, Reykjavik, Iceland.
EM krs2@hi.is
RI Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084
FU NIH [N01-AG-12100]; NIA Intramural Research Program; Hjartavernd (the
Icelandic Heart Association); Althingi (the Icelandic Parliament);
Icelandic Osteoarthritis Fund; University of Iceland Research Fund
FX Age, Gene/Environment Susceptibility Reykjavik Study (AGES-Reykjavik)
has been funded by NIH contract N01-AG-12100, the NIA Intramural
Research Program, Hjartavernd (the Icelandic Heart Association), and the
Althingi (the Icelandic Parliament), the Icelandic Osteoarthritis Fund
and the University of Iceland Research Fund. The study is approved by
the Icelandic National Bioethics Committee, (VSN: 00-063) and the Data
Protection Authority.
NR 31
TC 5
Z9 5
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2474
J9 BMC MUSCULOSKEL DIS
JI BMC Musculoskelet. Disord.
PD MAR 26
PY 2013
VL 14
AR 112
DI 10.1186/1471-2474-14-112
PG 5
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 124QP
UT WOS:000317480800002
PM 23530906
ER
PT J
AU Adamson, A
Ghoreschi, K
Rittler, M
Chen, Q
Sun, HW
Vahedi, G
Kanno, Y
Stetler-Stevenson, WG
O'Shea, JJ
Laurence, A
AF Adamson, Adewole
Ghoreschi, Kamran
Rittler, Matthew
Chen, Qian
Sun, Hong-Wei
Vahedi, Golnaz
Kanno, Yuka
Stetler-Stevenson, William G.
O'Shea, John J.
Laurence, Arian
TI Tissue Inhibitor of Metalloproteinase 1 Is Preferentially Expressed in
Th1 and Th17 T-Helper Cell Subsets and Is a Direct Stat Target Gene
SO PLOS ONE
LA English
DT Article
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; INFLAMMATORY-BOWEL-DISEASE;
MATRIX METALLOPROTEINASES; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS;
TGF-BETA; DIFFERENTIATION; CYTOKINE; T(H)17; TIMP-1
AB CD4(+) T helper (Th) cells differentiate into distinct effector subsets that are critical for host defense, but are also implicated in the pathogenesis of autoimmune disorders. Thelper17 (Th17) cells in particular are emerging as important drivers of multiple diseases including psoriasis, spondyloarthropathy and multiple sclerosis. To gain insight into the function of Th17 cells, we performed transcriptional profiling in hopes of elucidating products not previously recognized as being functionally relevant in these T cells. Herein, we demonstrate that tissue inhibitor of metalloproteinase 1 (TIMP1), a secreted protein with pleiotropic effects on cellular growth, survival and integrity of the extracellular matrix, is preferentially produced by Th17 and Th1 cells. We further show that Th1 and Th17 cell TIMP1 regulation follows separate mechanisms with a requirement for STAT4 in the former and STAT3 in the latter. Finally, we demonstrate that when restricted to T cells, expression of TIMP1 promotes neuropathology in experimental allergic encephalomyelitis.
C1 [Adamson, Adewole; Ghoreschi, Kamran; Sun, Hong-Wei; Vahedi, Golnaz; Kanno, Yuka; O'Shea, John J.; Laurence, Arian] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
[Rittler, Matthew; Stetler-Stevenson, William G.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Chen, Qian] Huazhong Univ Sci & Technol, Tongji Med Coll, Div Gastroenterol, Dept Internal Med, Wuhan, Hubei Province, Peoples R China.
[Adamson, Adewole] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Boston, MA USA.
[Ghoreschi, Kamran] Univ Tubingen, Dept Dermatol, Univ Med Ctr, Tubingen, Germany.
RP Laurence, A (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
EM laurencea@mail.nih.gov
RI Kanno, Yuka/B-5802-2013; Stetler-Stevenson, William/H-6956-2012;
Laurence, Arian/A-8770-2009;
OI Stetler-Stevenson, William/0000-0002-5500-5808; Laurence,
Arian/0000-0003-0942-8292; Kanno, Yuka/0000-0001-5668-9319
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases;
National Institutes of Health
FX This research was supported by intramural funding from the National
Institute of Arthritis and Musculoskeletal and Skin Diseases. AA was
supported by the National Institutes of Health Clinical Research
Training Program, a public-private partnership between the Foundation
for the National Institutes of Health and Pfizer Inc. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 48
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U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 26
PY 2013
VL 8
IS 3
AR e59367
DI 10.1371/journal.pone.0059367
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 123VE
UT WOS:000317418500036
PM 23555662
ER
PT J
AU Lan, Q
Cawthon, R
Gao, YT
Hu, W
Hosgood, HD
Barone-Adesi, F
Ji, BT
Bassig, B
Chow, WH
Shu, XO
Cai, QY
Xiang, YB
Berndt, S
Kim, C
Chanock, S
Zheng, W
Rothman, N
AF Lan, Qing
Cawthon, Richard
Gao, Yutang
Hu, Wei
Hosgood, H. Dean, III
Barone-Adesi, Francesco
Ji, Bu-Tian
Bassig, Bryan
Chow, Wong-Ho
Shu, Xiaoou
Cai, Qiuyin
Xiang, Yongbin
Berndt, Sonja
Kim, Christopher
Chanock, Stephen
Zheng, Wei
Rothman, Nathaniel
TI Longer Telomere Length in Peripheral White Blood Cells Is Associated
with Risk of Lung Cancer and the rs2736100 (CLPTM1L-TERT) Polymorphism
in a Prospective Cohort Study among Women in China
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MULTIPLEX QUANTITATIVE PCR; SUSCEPTIBILITY
LOCI; DNA-REPAIR; VARIANTS; 5P15.33; CHEMOTHERAPY; LYMPHOMA; BIOLOGY;
HEALTH
AB A recent genome-wide association study of lung cancer among never-smoking females in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on chromosome 5p15.33 was strongly and significantly associated with risk of adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. We previously found that longer telomere length measured in peripheral white blood cell DNA was associated with increased risk of lung cancer in a prospective cohort study of smoking males in Finland. To follow up on this finding, we carried out a nested case-control study of 215 female lung cancer cases and 215 female controls, 94% of whom were never-smokers, in the prospective Shanghai Women's Health Study cohort. There was a dose-response relationship between tertiles of telomere length and risk of lung cancer (odds ratio (OR), 95% confidence interval [CI]: 1.0, 1.4 [0.8-2.5], and 2.2 [1.2-4.0], respectively; P trend = 0.003). Further, the association was unchanged by the length of time from blood collection to case diagnosis. In addition, the rs2736100 G allele, which we previously have shown to be associated with risk of lung cancer in this cohort, was significantly associated with longer telomere length in these same study subjects (P trend = 0.030). Our findings suggest that individuals with longer telomere length in peripheral white blood cells may have an increased risk of lung cancer, but require replication in additional prospective cohorts and populations.
C1 [Lan, Qing; Hu, Wei; Hosgood, H. Dean, III; Barone-Adesi, Francesco; Ji, Bu-Tian; Bassig, Bryan; Chow, Wong-Ho; Berndt, Sonja; Kim, Christopher; Chanock, Stephen; Rothman, Nathaniel] NCI, NIH, DHHS, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Cawthon, Richard] Univ Utah, Dept Human Genet, Salt Lake City, UT USA.
[Gao, Yutang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Shu, Xiaoou; Cai, Qiuyin; Xiang, Yongbin; Zheng, Wei] Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol, Nashville, TN USA.
[Shu, Xiaoou; Cai, Qiuyin; Xiang, Yongbin; Zheng, Wei] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
RP Lan, Q (reprint author), NCI, NIH, DHHS, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM qingl@mail.nih.gov
RI Hu, Wei/M-3524-2013
FU National Cancer Institute (Bethesda, MD)
FX This work was supported by intramural funds from the National Cancer
Institute (Bethesda, MD). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 41
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U1 1
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 MAR 26
PY 2013
VL 8
IS 3
AR e59230
DI 10.1371/journal.pone.0059230
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 123VE
UT WOS:000317418500027
PM 23555636
ER
PT J
AU Miao, M
Wang, ZL
Yang, ZQ
Yuan, LL
Parker, DM
Putaporntip, C
Jongwutiwes, S
Xangsayarath, P
Pongvongsa, T
Moji, H
Tuong, TD
Abe, T
Nakazawa, S
Kyaw, MP
Yan, GY
Sirichaisinthop, J
Sattabongkot, J
Mu, JB
Su, XZ
Kaneko, O
Cui, LW
AF Miao, Miao
Wang, Zenglei
Yang, Zhaoqing
Yuan, Lili
Parker, Daniel M.
Putaporntip, Chaturong
Jongwutiwes, Somchai
Xangsayarath, Phonepadith
Pongvongsa, Tiengkham
Moji, Hazuhiko
Trinh Dinh Tuong
Abe, Tomoko
Nakazawa, Shusuke
Kyaw, Myat Phone
Yan, Guiyun
Sirichaisinthop, Jeeraphat
Sattabongkot, Jetsumon
Mu, Jianbing
Su, Xin-zhuan
Kaneko, Osamu
Cui, Liwang
TI Genetic Diversity and Lack of Artemisinin Selection Signature on the
Plasmodium falciparum ATP6 in the Greater Mekong Subregion
SO PLOS ONE
LA English
DT Article
ID SERCA-TYPE PFATPASE6; IN-VITRO; DNA POLYMORPHISM; POINT MUTATIONS;
NUCLEOTIDE SUBSTITUTIONS; COMBINATION THERAPIES; MITOCHONDRIAL-DNA;
RESISTANT MALARIA; S769N MUTATION; ARTESUNATE
AB The recent detection of clinical Artemisinin (ART) resistance manifested as delayed parasite clearance in the Cambodia-Thailand border area raises a serious concern. The mechanism of ART resistance is not clear; but the P. falciparum sarco/endoplasmic reticulum Ca2+-ATPase (PfSERCA or PfATP6) has been speculated to be the target of ARTs and thus a potential marker for ART resistance. Here we amplified and sequenced pfatp6 gene (similar to 3.6 Kb) in 213 samples collected after 2005 from the Greater Mekong Subregion, where ART drugs have been used extensively in the past. A total of 24 single nucleotide polymorphisms (SNPs), including 8 newly found in this study and 13 nonsynonymous, were identified. However, these mutations were either uncommon or also present in other geographical regions with limited ART use. None of the mutations were suggestive of directional selection by ARTs. We further analyzed pfatp6 from a worldwide collection of 862 P. falciparum isolates in 19 populations from Asia, Africa, South America and Oceania, which include samples from regions prior to and after deployments ART drugs. A total of 71 SNPs were identified, resulting in 106 nucleotide haplotypes. Similarly, many of the mutations were continent-specific and present at frequencies below 5%. The most predominant and perhaps the ancestral haplotype occurred in 441 samples and was present in 16 populations from Asia, Africa, and Oceania. The 3D7 haplotype found in 54 samples was the second most common haplotype and present in nine populations from all four continents. Assessment of the selection strength on pfatp6 in the 19 parasite populations found that pfatp6 in most of these populations was under purifying selection with an average dN/dS ratio of 0.333. Molecular evolution analyses did not detect significant departures from neutrality in pfatp6 for most populations, challenging the suitability of this gene as a marker for monitoring ART resistance.
C1 [Miao, Miao; Wang, Zenglei; Parker, Daniel M.; Cui, Liwang] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.
[Yang, Zhaoqing; Yuan, Lili] Kunming Med Coll, Dept Parasitol, Kunming, Yunnan, Peoples R China.
[Putaporntip, Chaturong; Jongwutiwes, Somchai] Chulalongkorn Univ, Dept Parasitol, Mol Biol Malaria & Opportunist Parasites Res Unit, Bangkok, Thailand.
[Xangsayarath, Phonepadith; Abe, Tomoko; Nakazawa, Shusuke; Kaneko, Osamu] Nagasaki Univ, Dept Protozool, Inst Trop Med NEKKEN, Nagasaki, Japan.
[Xangsayarath, Phonepadith; Abe, Tomoko; Nakazawa, Shusuke; Kaneko, Osamu] Nagasaki Univ, Global Ctr Excellence Program, Nagasaki, Japan.
[Pongvongsa, Tiengkham] Stn Malariol Parasitol & Entomol, Kaysone Dist, Savannakhet Pro, Laos.
[Moji, Hazuhiko] Res Inst Humanity & Nat, Kyoto, Japan.
[Trinh Dinh Tuong] Natl Inst Malariol Parasitol & Entomol, Dept Epidemiol, Hanoi, Vietnam.
[Kyaw, Myat Phone] Dept Med Res Lower Myanmar, Parasitol Res Div, Yangon, Myanmar.
[Yan, Guiyun] Univ Calif Irvine, Program Publ Hlth, Irvine, CA USA.
[Sirichaisinthop, Jeeraphat] Vector Borne Dis Training Ctr, Sara Buri, Thailand.
[Sattabongkot, Jetsumon] Mahidol Univ, Fac Trop Med, Bangkok, Thailand.
[Mu, Jianbing; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Cui, LW (reprint author), Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.
EM luc2@psu.edu
OI Parker, Daniel/0000-0002-5352-7338; Su, Xinzhuan/0000-0003-3246-3248
FU Divisions of Intramural Research, the National Institute of Allergy and
Infectious Diseases, National Institutes of Health [U19 AI089672,
1R01AI075429]
FX This project was supported by grants (U19 AI089672 and 1R01AI075429) and
by the Divisions of Intramural Research, the National Institute of
Allergy and Infectious Diseases, 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 67
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U1 0
U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 26
PY 2013
VL 8
IS 3
AR e59192
DI 10.1371/journal.pone.0059192
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 123VE
UT WOS:000317418500024
PM 23555629
ER
PT J
AU Ronda, L
Bettati, S
Henry, ER
Kashav, T
Sanders, JM
Royer, WE
Mozzarelli, A
AF Ronda, Luca
Bettati, Stefano
Henry, Eric R.
Kashav, Tara
Sanders, Jeffrey M.
Royer, William E.
Mozzarelli, Andrea
TI Tertiary and Quaternary Allostery in Tetrameric Hemoglobin from
Scapharca inaequivalvis
SO BIOCHEMISTRY
LA English
DT Article
ID COOPERATIVE DIMERIC HEMOGLOBIN; T-STATE HEMOGLOBIN; OXYGEN-BINDING;
SILICA-GELS; FUNCTIONAL-CHARACTERIZATION; AFFINITY CONFORMATIONS;
CRYSTAL-STRUCTURE; SINGLE-CRYSTALS; HEME-PROTEINS; RESOLUTION
AB The clam Scapharca inaequivalvis possesses two cooperative oxygen binding hemoglobins in its red cells: a homodimeric HbI and a heterotetrameric A2B2 HbII, Each AB dimeric half of HbII is assembled in a manner very similar to that of the well-studied HbI. This study presents crystal structures of HbII along with oxygen binding data both in the crystalline state and in wet nanoporous silica gels. Despite very similar ligand-linked structural transitions observed in HbI and HbII crystals, HbII in the crystal or encapsulated in silica gels apparently exhibits minimal cooperativity in oxygen binding, in contrast with the full cooperativity exhibited by HbI crystals. However, oxygen binding curves in the crystal indicate the presence of a significant functional inequivalence of A and B chains. When this inequivalence is taken into account, both crystal and R state gel functional data are consistent with the conservation of a tertiary contribution to cooperative oxygen binding, quantitatively similar to that measured for HbI, and are in keeping with the structural information. Furthermore, our results indicate that to fully express cooperative ligand binding, HbII requires quaternary transitions hampered by crystal lattice and gel encapsulation, revealing greater complexity in cooperative function than the direct communication across a dimeric interface observed in HbI.
C1 [Ronda, Luca; Mozzarelli, Andrea] Univ Parma, Dept Pharm, I-43124 Parma, Italy.
[Bettati, Stefano] Univ Parma, Dept Neurosci, I-43125 Parma, Italy.
[Bettati, Stefano; Mozzarelli, Andrea] Natl Inst Biostruct & Biosyst, I-00136 Rome, Italy.
[Henry, Eric R.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Kashav, Tara; Sanders, Jeffrey M.; Royer, William E.] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA.
RP Royer, WE (reprint author), Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, 364 Plantat St,LRB921, Worcester, MA 01605 USA.
EM andrea.mozzarelli@unipr.it
RI Henry, Eric/J-3414-2013; Ronda, Luca/E-5214-2012; Mozzarelli,
Andrea/C-3615-2014;
OI Henry, Eric/0000-0002-5648-8696; Mozzarelli, Andrea/0000-0003-3762-0062;
Ronda, Luca/0000-0002-5389-2669
FU U.S. Department of Energy, Basic Energy Sciences, Office of Science
[DE-AC02-06CH11357]; National Center for Research Resources
[5P41RR007707]; National Institute of General Medical Sciences from the
National Institutes of Health [8P41GM103543]
FX We thank Drs. Gianni Colotti and Emilia Chiancone for the generous gift
of purified HbII. Use of the Advanced Photon Source was supported by the
U.S. Department of Energy, Basic Energy Sciences, Office of Science,
under Contract DE-AC02-06CH11357. Use of BioCARS Sector 14 was also
supported by grants from the National Center for Research Resources
(5P41RR007707) and the National Institute of General Medical Sciences
(8P41GM103543) from the National Institutes of Health.
NR 53
TC 2
Z9 2
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 MAR 26
PY 2013
VL 52
IS 12
BP 2108
EP 2117
DI 10.1021/bi301620x
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 115YC
UT WOS:000316846800010
PM 23458680
ER
PT J
AU Zhang, FM
Walcott, B
Zhou, DW
Gustchina, A
Lasanajak, Y
Smith, DF
Ferreira, RS
Correia, MTS
Paiva, PMG
Bovin, NV
Wlodawer, A
Oliva, MLV
Linhardt, RJ
AF Zhang, Fuming
Walcott, Benjamin
Zhou, Dongwen
Gustchina, Alla
Lasanajak, Yi
Smith, David F.
Ferreira, Rodrigo S.
Correia, Maria Tereza S.
Paiva, Patricia M. G.
Bovin, Nicolai V.
Wlodawer, Alexander
Oliva, Maria L. V.
Linhardt, Robert J.
TI Structural Studies of the Interaction of Crataeva tapia Bark Protein
with Heparin and Other Glycosaminoglycans
SO BIOCHEMISTRY
LA English
DT Article
ID BINDING LECTIN; HEPARIN/HEPARAN SULFATE
AB CrataBL, a protein isolated from Crataeva tapia bark, which is both a serine protease inhibitor and a lectin, has been previously shown to exhibit a number of interesting biological properties, including anti-inflammatory, analgesic, antitumor, and insecticidal activities. Using a glycan array, we have now shown that only sulfated carbohydrates are effectively bound by CrataBL. Because this protein was recently shown to delay clot formation by impairing the intrinsic pathway of the coagulation cascade, we considered that its natural ligand might be heparin. Heparin is a glycosaminoglycan (GAG) that interacts with a number of proteins, including thrombin and antithrombin III, which have a critical, essential pharmacological role in regulating blood coagulation. We have thus employed surface plasmon resonance to improve our understanding of the binding interaction between the heparin polysaccharide and CrataBL. Kinetic analysis shows that CrataBL displays strong heparin binding affinity (K-D = 49 nM). Competition studies using different size heparin-derived oligosaccharides showed that the binding of CrataBL to heparin is chain length-dependent. Full chain heparin with 40 saccharides or large oligosaccharides, having 16-18 saccharide residues, show strong binding affinity for CrataBL. Heparin-derived disaccharides through tetradecasaccharides show considerably lower binding affinity. Other highly sulfated GAGs, including chondroitin sulfate E and dermatan 4,6-disulfate, showed CrataBL binding affinity comparable to that of heparin. Less highly sulfated GAGs, heparan sulfate, chondroitin sulfate A and C, and dermatan sulfate displayed modest binding affinity as did chondroitin sulfate D. Studies using chemically modified heparin show that N-sulfo and 6-O-sulfo groups on heparin are essential for CrataBL-heparin interaction.
C1 [Zhang, Fuming; Walcott, Benjamin; Linhardt, Robert J.] Rensselaer Polytech Inst, Dept Chem & Biol Engn, Dept Chem & Chem Biol, Ctr Biotechnol & Interdisciplinary Studies,Dept B, Troy, NY 12180 USA.
[Zhou, Dongwen; Gustchina, Alla; Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
[Lasanajak, Yi; Smith, David F.] Emory Univ, Sch Med, Dept Biochem, Glyc Ctr, Atlanta, GA 30322 USA.
[Ferreira, Rodrigo S.; Oliva, Maria L. V.] Univ Fed Sao Paulo, Dept Bioquim, BR-04044020 Sao Paulo, Brazil.
[Correia, Maria Tereza S.; Paiva, Patricia M. G.] Univ Fed Pernambuco, Dept Bioquim, BR-50670901 Recife, PE, Brazil.
[Bovin, Nicolai V.] Russian Acad Sci, Inst Bioorgan Chem, Lab Carbohydrate Chem, Moscow 117997, Russia.
RP Zhang, FM (reprint author), Rensselaer Polytech Inst, Dept Chem & Biol Engn, Dept Chem & Chem Biol, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.
EM zhangf2@rpi.edu; linhar@rpi.edu
RI Ferreira, Rodrigo/C-1763-2013; Oliva, Maria Luiza/B-9537-2012;
OI Ferreira, Rodrigo/0000-0003-4103-6870; Walcott,
Benjamin/0000-0001-9374-9149; Paiva, Patricia/0000-0003-3467-708X
FU National Institutes of Health (NIH) [GM-38060]; Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research; Molecular and Cell Biology grant (Presidium RAS); CAPES; CNPq;
FAPESP [09/53766-5]; National Institute of General Medical Sciences
[GM62116, GM98791]
FX This work was supported in part by a grant from the National Institutes
of Health (NIH) (GM-38060 to R.J.L.), in part by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research, and in part by a Molecular and Cell Biology grant (Presidium
RAS) to N.V.B. We are also grateful to CAPES, CNPq, and FAPESP (Process
09/53766-5) for providing financial support.; We acknowledge The
Consortium for Functional Glycomics funded by National Institute of
General Medical Sciences Grants GM62116 and GM98791 for services
provided by the Glycan Array Synthesis Core (The Scripps Research
Institute, La Jolla, CA) that produced the mammalian glycan microarray
and the Protein-Glycan Interaction Core (Emory University School of
Medicine) that assisted with analysis of samples on the array.
NR 30
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Z9 5
U1 2
U2 26
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAR 26
PY 2013
VL 52
IS 12
BP 2148
EP 2156
DI 10.1021/bi400077b
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 115YC
UT WOS:000316846800014
PM 23448527
ER
PT J
AU Budoff, MJ
Young, R
Lopez, VA
Kronmal, RA
Nasir, K
Blumenthal, RS
Detrano, RC
Bild, DE
Guerci, AD
Liu, K
Shea, S
Szklo, M
Post, W
Lima, J
Bertoni, A
Wong, ND
AF Budoff, Matthew J.
Young, Rebekah
Lopez, Victor A.
Kronmal, Richard A.
Nasir, Khurram
Blumenthal, Roger S.
Detrano, Robert C.
Bild, Diane E.
Guerci, Alan D.
Liu, Kiang
Shea, Steven
Szklo, Moyses
Post, Wendy
Lima, Joao
Bertoni, Alain
Wong, Nathan D.
TI Progression of Coronary Calcium and Incident Coronary Heart Disease
Events MESA (Multi-Ethnic Study of Atherosclerosis)
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE atherosclerosis; coronary calcification; coronary heart disease; imaging
ID BEAM COMPUTED-TOMOGRAPHY; ARTERY CALCIUM; MULTIPLE IMPUTATION;
MYOCARDIAL-INFARCTION; SURVIVAL ANALYSIS; LOWERING THERAPY;
CALCIFICATION; RISK; PREDICTS; ADULTS
AB Objectives The study examined whether progression of coronary artery calcium (CAC) is a predictor of future coronary heart disease (CHD) events.
Background CAC predicts CHD events and serial measurement of CAC has been proposed to evaluate atherosclerosis progression.
Methods We studied 6,778 persons (52.8% female) aged 45 to 84 years from the MESA (Multi-Ethnic Study of Atherosclerosis) study. A total of 5,682 persons had baseline and follow-up CAC scans approximately 2.5 +/- 0.8 years apart; multiple imputation was used to account for the remainder (n = 1,096) missing follow-up scans. Median follow-up duration from the baseline was 7.6 (max = 9.0) years. CAC change was assessed by absolute change between baseline and follow-up CAC. Cox proportional hazards regression providing hazard ratios (HRs) examined the relation of change in CAC with CHD events, adjusting for age, gender, ethnicity, baseline calcium score, and other risk factors.
Results A total of 343 and 206 hard CHD events occurred. The annual change in CAC averaged 24.9 +/- 65.3 Agatston units. Among persons without CAC at baseline (n = 3,396), a 5-unit annual change in CAC was associated with an adjusted HR (95% Confidence Interval) of 1.4 (1.0 to 1.9) for total and 1.5 (1.1 to 2.1) for hard CHD. Among those with CAC >0 at baseline, HRs (per 100 unit annual change) were 1.2 (1.1 to 1.4) and 1.3 (1.1 to 1.5), respectively. Among participants with baseline CAC, those with annual progression of >= 300 units had adjusted HRs of 3.8 (1.5 to 9.6) for total and 6.3 (1.9 to 21.5) for hard CHD compared to those without progression.
Conclusions Progression of CAC is associated with an increased risk for future hard and total CHD events. (J Am Coll Cardiol 2013;61:1231-9) (C) 2013 by the American College of Cardiology Foundation
C1 [Budoff, Matthew J.; Nasir, Khurram] Harbor UCLA Med Ctr, Div Cardiol, LA Biomed Res Inst, Los Angeles, CA USA.
[Young, Rebekah; Kronmal, Richard A.] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA.
[Lopez, Victor A.; Detrano, Robert C.; Wong, Nathan D.] Univ Calif Irvine, Dept Radiol, Irvine, CA 92697 USA.
[Nasir, Khurram; Blumenthal, Roger S.; Post, Wendy; Lima, Joao] Johns Hopkins Univ, Dept Cardiol, Baltimore, MD USA.
[Nasir, Khurram] Baptist Hlth Med Grp, Ctr Prevent & Wellness Res, Miami Beach, FL USA.
[Nasir, Khurram] Florida Int Univ, Robert Stempel Coll Publ Hlth, Dept Epidemiol, Miami, FL 33199 USA.
[Nasir, Khurram] Florida Int Univ, Dept Med, Herbert Wertheim Coll Med, Miami, FL 33199 USA.
[Bild, Diane E.] NHLBI, Prevent & Populat Studies Program, Bethesda, MD 20892 USA.
[Guerci, Alan D.] St Francis Hosp, Ctr Heart, Roslyn, NY USA.
[Liu, Kiang] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
[Shea, Steven] Columbia Univ, Dept Med, New York, NY USA.
[Szklo, Moyses] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Bertoni, Alain] Wake Forest Univ, Dept Med, Wake Forest, NC USA.
RP Wong, ND (reprint author), Univ Calif Irvine, Dept Med, Heart Dis Prevent Program, Sprague Hall 112, Irvine, CA 92697 USA.
EM ndwong@uci.edu
FU NHLBI [N01-HC-95159, N01-HC-95169]
FX This research was supported by NHLBI contracts N01-HC-95159 through
N01-HC-95169. Dr. Budoff is a consultant for General Electric. Dr. Wong
is a consultant for Re-Engineering Healthcare, Inc. All other authors
have reported that they have no relationships relevant to the contents
of this paper to disclose. Paolo Raggi, MD, served as the Guest Editor
for this article.
NR 33
TC 72
Z9 73
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 26
PY 2013
VL 61
IS 12
BP 1231
EP 1239
DI 10.1016/j.jacc.2012.12.035
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 114OK
UT WOS:000316751100004
PM 23500326
ER
PT J
AU Silman, I
Roth, E
Paz, A
Triquigneaux, MM
Ehrenshaft, M
Xu, YC
Shnyrov, VL
Sussman, JL
Deterding, LJ
Ashani, Y
Mason, RP
Weiner, L
AF Silman, Israel
Roth, Esther
Paz, Aviv
Triquigneaux, Mathilde M.
Ehrenshaft, Marilyn
Xu, Yechun
Shnyrov, Valery L.
Sussman, Joel L.
Deterding, Leesa J.
Ashani, Yacov
Mason, Ronald P.
Weiner, Lev
TI The specific interaction of the photosensitizer methylene blue with
acetylcholinesterase provides a model system for studying the molecular
consequences of photodynamic therapy
SO CHEMICO-BIOLOGICAL INTERACTIONS
LA English
DT Article; Proceedings Paper
CT International Meeting on Cholinesterases
CY JUN 04-09, 2012
CL Kazan, RUSSIA
DE Acetylcholinesterase; Methylene blue; Photosensitizer; Photodynamic
therapy; Mass spectroscopy; Singlet oxygen
ID TORPEDO-CALIFORNICA ACETYLCHOLINESTERASE; ACTIVE-SITE GORGE; SINGLET
OXYGEN; N-FORMYLKYNURENINE; TARGETED OXIDATION; LIGAND-BINDING; STATE;
SUBSTRATE; PROTEINS; COMPLEX
AB The photosensitizer, methylene blue (MB), generates singlet oxygen (O-1(2)) that irreversibly inhibits Torpedo californica acetylcholinesterase (TcAChE). In the dark MB inhibits reversibly, binding being accompanied by a bathochromic shift that can be used to show its displacement by other reversible inhibitors binding to the catalytic 'anionic' subsite (CAS), the peripheral 'anionic' subsite (PAS), or bridging them. Data concerning both reversible and irreversible inhibition are here reviewed. MB protects TcAChE from thermal denaturation, and differential scanning calorimetry reveals a similar to 8 degrees C increase in the denaturation temperature. The crystal structure of the MB/TcAChE complex reveals a single MB stacked against W279 in the PAS, pointing down the gorge towards the CAS. The intrinsic fluorescence of the irreversibly inhibited enzyme displays new emission bands that can be ascribed to N'-formylkynurenine (NFK); this was indeed confirmed using anti-NFK antibodies. Mass spectroscopy revealed that two Trp residues, Trp84 in the CAS, and Trp279 in the PAS, were the only Trp residues, out of a total of 14, significantly modified by photo-oxidation, both being converted to NFK. In the presence of competitive inhibitors that displace MB from the gorge, their modification is completely prevented. Thus, photo-oxidative damage caused by MB involves targeted release of O-1(2) by the bound photosensitizer within the aqueous milieu of the active-site gorge. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Silman, Israel; Roth, Esther; Paz, Aviv; Xu, Yechun; Ashani, Yacov] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel.
[Paz, Aviv; Xu, Yechun; Sussman, Joel L.] Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel.
[Triquigneaux, Mathilde M.; Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Shnyrov, Valery L.] Univ Salamanca, Dept Biochem & Mol Biol, Salamanca 37007, Spain.
[Deterding, Leesa J.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Weiner, Lev] Weizmann Inst Sci, Dept Chem Res Support, IL-76100 Rehovot, Israel.
RP Silman, I (reprint author), Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel.
EM israel.silman@weizmann.ac.il
OI Sussman, Joel/0000-0003-0306-3878
NR 32
TC 2
Z9 2
U1 1
U2 28
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0009-2797
EI 1872-7786
J9 CHEM-BIOL INTERACT
JI Chem.-Biol. Interact.
PD MAR 25
PY 2013
VL 203
IS 1
SI SI
BP 63
EP 66
DI 10.1016/j.cbi.2012.10.021
PG 4
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
GA 134HU
UT WOS:000318201800014
PM 23159732
ER
PT J
AU Quick, V
Wall, M
Larson, N
Haines, J
Neumark-Sztainer, D
AF Quick, Virginia
Wall, Melanie
Larson, Nicole
Haines, Jess
Neumark-Sztainer, Dianne
TI Personal, behavioral and socio-environmental predictors of overweight
incidence in young adults: 10-yr longitudinal findings
SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY
LA English
DT Article
DE Adolescents; Young adults; Overweight; Weight control
ID FOOD FREQUENCY QUESTIONNAIRE; BODY-MASS INDEX; PROJECT EAT; ADOLESCENT
OVERWEIGHT; PROTECTIVE FACTORS; WEIGHT CHANGE; SHARED RISK; OBESITY;
CONSUMPTION; REPRODUCIBILITY
AB Background: The objective of this study was to identify 10-year longitudinal predictors of overweight incidence during the transition from adolescence to young adulthood.
Methods: Data were from Project EAT (Eating and Activity in Teens and Young Adults). A diverse, population-based cohort (N = 2,134) completed baseline surveys in 1998-1999 (mean age = 15.0 +/- 1.6, 'adolescence') and follow-up surveys in 2008-2009 (mean age = 25.4 +/- 1.7, 'young adulthood'). Surveys assessed personal, behavioral and socio-environmental factors hypothesized to be of relevance to obesity, in addition to height and weight. Multivariable logistic regression was used to estimate the adjusted odds for each personal, behavioral and socio-environmental factor at baseline, and 10-year changes for these factors, among non-overweight adolescents (n = 1,643) being predictive of the incidence of overweight (BMI >= 25) at 10-year follow-up.
Results: At 10-year follow-up, 51% of young adults were overweight (26% increase from baseline). Among females and males, higher levels of body dissatisfaction, weight concerns, unhealthy weight control behaviors (e.g., fasting, purging), dieting, binge eating, weight-related teasing, and parental weight-related concerns and behaviors during adolescence and/or increases in these factors over the study period predicted the incidence of overweight at 10-year follow-up. Females with higher levels of whole grain intake and breakfast and dinner consumption frequency during adolescence were protected against becoming overweight. Among males, increases in vegetable intake protected against the incidence of overweight 10 years later.
Conclusions: Findings suggest that obesity prevention interventions for adolescents should address weight-specific factors from within the domains of personal, behavioral, and socio-environmental factors such as promoting positive body image, decreasing unhealthy weight control behaviors, and limiting negative weight talk.
C1 [Quick, Virginia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Bethesda, MD 20892 USA.
[Larson, Nicole; Neumark-Sztainer, Dianne] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA.
[Wall, Melanie] Univ Minnesota, Div Biostat, Sch Publ Hlth, Minneapolis, MN 55454 USA.
[Haines, Jess] Univ Guelph, Guelph, ON N1G 2W1, Canada.
RP Quick, V (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Bethesda, MD 20892 USA.
EM gingermquick@gmail.com
OI Quick, Virginia/0000-0002-4338-963X; Neumark-Sztainer,
Dianne/0000-0001-9435-1669
FU National Heart, Lung, and Blood Institute [R01HL084064]; National
Research Service Award (NRSA) in Primary Medical Care [T32HP22239];
Bureau of Health Professions; Health Resources and Services
Administration; Department of Health and Human Services
FX This study was supported by Grant Number R01HL084064 from the National
Heart, Lung, and Blood Institute (PI: Dianne Neumark-Sztainer). The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Heart, Lung,
and Blood Institute or the National Institutes of Health. The first
author's time was supported by a National Research Service Award (NRSA)
in Primary Medical Care, Grant Number T32HP22239 (PI: Irene Borowsky),
Bureau of Health Professions, Health Resources and Services
Administration, Department of Health and Human Services.
NR 48
TC 26
Z9 26
U1 4
U2 28
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 MAR 25
PY 2013
VL 10
AR 37
DI 10.1186/1479-5868-10-37
PG 13
WC Nutrition & Dietetics; Physiology
SC Nutrition & Dietetics; Physiology
GA 126UA
UT WOS:000317645500002
PM 23531253
ER
PT J
AU Rackoff, LA
Bok, K
Green, KY
Kapikian, AZ
AF Rackoff, Lauren A.
Bok, Karin
Green, Kim Y.
Kapikian, Albert Z.
TI Epidemiology and Evolution of Rotaviruses and Noroviruses from an
Archival WHO Global Study in Children (1976-79) with Implications for
Vaccine Design
SO PLOS ONE
LA English
DT Article
ID INFECTIOUS NONBACTERIAL GASTROENTERITIS; POLYMERASE CHAIN-REACTION;
PHYLOGENETIC ANALYSIS; MAXIMUM-LIKELIHOOD; VP7 GENE; RT-PCR; VIRUS;
GENOTYPE; NORWALK; STRAIN
AB Prompted by the discovery of new gastrointestinal viruses, the NIH, NIAID and WHO investigated the etiology of acute diarrhea that occurred from 1976-1979 in a global cohort of infants and young children. Rotaviruses were found to be major pathogens worldwide, whereas the Norwalk virus could not be detected using a radioimmunoassay. The aim of this study is to re-evaluate the role and diversity of rotaviruses and noroviruses in the original cohort using more sensitive current technologies. Stools collected from Asia, Africa, and South America (n = 485) were evaluated for viral genotypes by RT-PCR and sequencing. Rotaviruses were detected in 28.9% and noroviruses in 9.7% of the specimens, with G1 rotaviruses and GII noroviruses accounting for the majority of each respective virus. Various strains in this study predated the currently assigned dates of discovery for their particular genotype, and in addition, two noroviruses (KL45 and T091) could not be assigned to current genotypes. Phylogenetic analyses demonstrated a relative constancy in circulating rotavirus genotypes over time, with several genotypes from this study becoming established in the current repertoire of viral species. Similarly, GII noroviruses have maintained dominance, with GII. 4 noroviruses continuing as a predominant genotype over time. Taken together, the complex molecular epidemiology of rotaviruses and noroviruses circulating in the 1970's is consistent with current patterns, an important consideration in the design of multivalent vaccines to control these viruses.
C1 [Rackoff, Lauren A.; Bok, Karin; Green, Kim Y.; Kapikian, Albert Z.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Green, KY (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kgreen@niaid.nih.gov
FU Division of Intramural Research (DIR) of NIAID, NIH
FX The work was funded by the Division of Intramural Research (DIR) of
NIAID, NIH. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 61
TC 22
Z9 23
U1 0
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 MAR 25
PY 2013
VL 8
IS 3
AR e59394
DI 10.1371/journal.pone.0059394
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 123NP
UT WOS:000317397200023
PM 23536875
ER
PT J
AU Yang, ZH
Grinchuk, V
Urban, JF
Bohl, J
Sun, R
Notari, L
Yan, S
Ramalingam, T
Keegan, AD
Wynn, TA
Shea-Donohue, T
Zhao, AP
AF Yang, Zhonghan
Grinchuk, Viktoriya
Urban, Joseph F., Jr.
Bohl, Jennifer
Sun, Rex
Notari, Luigi
Yan, Shu
Ramalingam, Thirumalai
Keegan, Achsah D.
Wynn, Thomas A.
Shea-Donohue, Terez
Zhao, Aiping
TI Macrophages as IL-25/IL-33-Responsive Cells Play an Important Role in
the Induction of Type 2 Immunity
SO PLOS ONE
LA English
DT Article
ID ALTERNATIVELY ACTIVATED MACROPHAGES; NIPPOSTRONGYLUS-BRASILIENSIS
INFECTION; ADAPTIVE IMMUNITY; SMALL-INTESTINE; LYMPHOID-CELLS; IN-VIVO;
CYTOKINE; EXPRESSION; RECEPTOR; DISEASE
AB Type 2 immunity is essential for host protection against nematode infection but is detrimental in allergic inflammation or asthma. There is a major research focus on the effector molecules and specific cell types involved in the initiation of type 2 immunity. Recent work has implicated an important role of epithelial-derived cytokines, IL-25 and IL-33, acting on innate immune cells that are believed to be the initial sources of type 2 cytokines IL-4/IL-5/IL-13. The identities of the cell types that mediate the effects of IL-25/IL-33, however, remain to be fully elucidated. In the present study, we demonstrate that macrophages as IL-25/IL-33-responsive cells play an important role in inducing type 2 immunity using both in vitro and in vivo approaches. Macrophages produced type 2 cytokines IL-5 and IL-13 in response to the stimulation of IL-25/IL-33 in vitro, or were the IL-13-producing cells in mice administrated with exogenous IL-33 or infected with Heligmosomoides bakeri. In addition, IL-33 induced alternative activation of macrophages primarily through autocrine IL-13 activating the IL-4R alpha-STAT6 pathway. Moreover, depletion of macrophages attenuated the IL-25/IL-33-induced type 2 immunity in mice, while adoptive transfer of IL-33-activated macrophages into mice with a chronic Heligmosomoides bakeri infection induced worm expulsion accompanied by a potent type 2 protective immune response. Thus, macrophages represent a unique population of the innate immune cells pivotal to type 2 immunity and a potential therapeutic target in controlling type 2 immunity-mediated inflammatory pathologies.
C1 [Yang, Zhonghan; Grinchuk, Viktoriya; Bohl, Jennifer; Sun, Rex; Notari, Luigi; Yan, Shu; Shea-Donohue, Terez; Zhao, Aiping] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Yang, Zhonghan; Grinchuk, Viktoriya; Bohl, Jennifer; Sun, Rex; Notari, Luigi; Yan, Shu; Shea-Donohue, Terez; Zhao, Aiping] Univ Maryland, Sch Med, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA.
[Yang, Zhonghan] Sun Yat Sen Univ, Dept Biochem, Zhongshan Med Sch, Guangzhou 510275, Guangdong, Peoples R China.
[Urban, Joseph F., Jr.] ARS, USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD USA.
[Keegan, Achsah D.] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA.
[Ramalingam, Thirumalai; Wynn, Thomas A.] NIAID, Div Parasitol, NIH, Bethesda, MD 20892 USA.
RP Zhao, AP (reprint author), Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
EM azhao@mbrc.umaryland.edu
OI Urban, Joseph/0000-0002-1590-8869
FU NIH [R01-DK083418, R01-AI/DK49316, R01-AI038985]; USDA CRIS
[1235-51000-055]
FX This work was supported by NIH grants R01-DK083418 (AZ), R01-AI/DK49316
(T. S-D), R01-AI038985 (ADK), and USDA CRIS project #1235-51000-055
(JFU). The opinions and assertions in this article are those of the
authors and do not necessarily represent those of the U. S. Department
of Agriculture or the Department of Defense. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 44
TC 36
Z9 38
U1 0
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 MAR 25
PY 2013
VL 8
IS 3
AR e59441
DI 10.1371/journal.pone.0059441
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 123NP
UT WOS:000317397200025
PM 23536877
ER
PT J
AU Mur, M
Meys, M
Bodurka, J
Goebel, R
Bandettini, PA
Kriegeskorte, N
AF Mur, Marieke
Meys, Mirjam
Bodurka, Jerzy
Goebel, Rainer
Bandettini, Peter A.
Kriegeskorte, Nikolaus
TI Human object-similarity judgments reflect and transcend the primate-IT
object representation
SO FRONTIERS IN PSYCHOLOGY
LA English
DT Article
DE object perception; vision; neuronal representation; fMRI;
representational similarity analysis; human; primate
ID INFERIOR TEMPORAL CORTEX; PREFRONTAL CORTEX; CORTICAL REPRESENTATION;
INFEROTEMPORAL CORTEX; VISUAL-CORTEX; HUMAN BRAIN; SHAPES;
CATEGORIZATION; ORGANIZATION; FEATURES
AB Primate inferior temporal (IT) cortex is thought to contain a high-level representation of objects at the interface between vision and semantics. This suggests that the perceived similarity of real-world objects might be predicted from the IT representation. Here we show that objects that elicit similar activity patterns in human IT (hIT) tend to be judged as similar by humans. The IT representation explained the human judgments better than early visual cortex, other ventral-stream regions, and a range of computational models. Human similarity judgments exhibited category clusters that reflected several categorical divisions that are prevalent in the IT representation of both human and monkey, including the animate/inanimate and the face/body division. Human judgments also reflected the within-category representation of IT. However, the judgments transcended the IT representation in that they introduced additional categorical divisions. In particular, human judgments emphasized human-related additional divisions between human and non-human animals and between man-made and natural objects. hIT was more similar to monkey IT than to human judgments. One interpretation is that IT has evolved visual-feature detectors that distinguish between animates and inanimates and between faces and bodies because these divisions are fundamental to survival and reproduction for all primate species, and that other brain systems serve to more flexibly introduce species-dependent and evolutionarily more recent divisions.
C1 [Mur, Marieke; Meys, Mirjam; Bandettini, Peter A.; Kriegeskorte, Nikolaus] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Mur, Marieke; Meys, Mirjam; Goebel, Rainer] Maastricht Univ, Fac Psychol & Neurosci, Dept Cognit Neurosci, Maastricht, Netherlands.
[Mur, Marieke; Kriegeskorte, Nikolaus] MRC, Cognit & Brain Sci Unit, Cambridge CB2 7EF, England.
[Bodurka, Jerzy; Bandettini, Peter A.] NIMH, Funct Magnet Resonance Imaging Facil, NIH, Bethesda, MD 20892 USA.
RP Kriegeskorte, N (reprint author), MRC, Cognit & Brain Sci Unit, 15 Chaucer Rd, Cambridge CB2 7EF, England.
EM nikolaus.kriegeskorte@mrc-cbu.cam.ac.uk
OI Kriegeskorte, Nikolaus/0000-0001-7433-9005
FU Medical Research Council [MC_U105597120]
NR 56
TC 22
Z9 22
U1 1
U2 10
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-1078
J9 FRONT PSYCHOL
JI Front. Psychol.
PD MAR 22
PY 2013
VL 4
AR 128
DI 10.3389/fpsyg.2013.00128
PG 22
WC Psychology, Multidisciplinary
SC Psychology
GA AA0TM
UT WOS:000330810300001
PM 23525516
ER
PT J
AU Richardson, DB
Volkow, ND
Kwan, MP
Kaplan, RM
Goodchild, MF
Croyle, RT
AF Richardson, Douglas B.
Volkow, Nora D.
Kwan, Mei-Po
Kaplan, Robert M.
Goodchild, Michael F.
Croyle, Robert T.
TI Spatial Turn in Health Research
SO SCIENCE
LA English
DT Editorial Material
C1 [Richardson, Douglas B.] AAG, Washington, DC 20009 USA.
[Volkow, Nora D.] NIDA, NIH, Rockville, MD 20852 USA.
[Kwan, Mei-Po] Univ Illinois, Dept Geog & Geog Informat Sci, Urbana, IL 61801 USA.
[Kaplan, Robert M.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Goodchild, Michael F.] Univ Calif Santa Barbara, Dept Geog, Santa Barbara, CA 93106 USA.
[Croyle, Robert T.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
RP Richardson, DB (reprint author), AAG, 1710 16th St NW, Washington, DC 20009 USA.
EM drichardson@aag.org
FU NCI NIH HHS [R13CA162823, R13 CA162823]
NR 20
TC 48
Z9 51
U1 7
U2 75
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 MAR 22
PY 2013
VL 339
IS 6126
BP 1390
EP 1392
DI 10.1126/science.1232257
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 114KU
UT WOS:000316740700028
PM 23520099
ER
PT J
AU Shnyrova, AV
Bashkirov, PV
Akimov, SA
Pucadyil, TJ
Zimmerberg, J
Schmid, SL
Frolov, VA
AF Shnyrova, Anna V.
Bashkirov, Pavel V.
Akimov, Sergey A.
Pucadyil, Thomas J.
Zimmerberg, Joshua
Schmid, Sandra L.
Frolov, Vadim A.
TI Geometric Catalysis of Membrane Fission Driven by Flexible Dynamin Rings
SO SCIENCE
LA English
DT Article
ID DEPENDENT CONFORMATIONAL-CHANGES; CRYSTAL-STRUCTURE; CONSTRICTION;
REVEALS; FUSION; SHAPE
AB Biological membrane fission requires protein-driven stress. The guanosine triphosphatase (GTPase) dynamin builds up membrane stress by polymerizing into a helical collar that constricts the neck of budding vesicles. How this curvature stress mediates nonleaky membrane remodeling is actively debated. Using lipid nanotubes as substrates to directly measure geometric intermediates of the fission pathway, we found that GTP hydrolysis limits dynamin polymerization into short, metastable collars that are optimal for fission. Collars as short as two rungs translated radial constriction to reversible hemifission via membrane wedging of the pleckstrin homology domains (PHDs) of dynamin. Modeling revealed that tilting of the PHDs to conform with membrane deformations creates the low-energy pathway for hemifission. This local coordination of dynamin and lipids suggests how membranes can be remodeled in cells.
C1 [Shnyrova, Anna V.; Frolov, Vadim A.] Univ Basque Country, CSIC, Biophys Unit, Leioa, Spain.
[Shnyrova, Anna V.; Frolov, Vadim A.] Univ Basque Country, Dept Biochem & Mol Biol, Leioa, Spain.
[Bashkirov, Pavel V.; Akimov, Sergey A.] Russian Acad Sci, AN Frumkin Inst Phys Chem & Electrochem, Moscow 119071, Russia.
[Akimov, Sergey A.] Natl Univ Sci & Technol MISiS, Moscow 119049, Russia.
[Pucadyil, Thomas J.] Indian Inst Sci Educ & Res, Pune, Maharashtra, India.
[Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Schmid, Sandra L.] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA.
[Frolov, Vadim A.] Basque Fdn Sci, IKERBASQUE, Bilbao, Spain.
RP Frolov, VA (reprint author), Univ Basque Country, CSIC, Biophys Unit, Leioa, Spain.
EM vadim.frolov@ehu.es
RI Akimov, Sergey/L-2001-2013; Akimov, Sergey/I-6432-2015;
OI Frolov, Vadim/0000-0002-0653-5669; Pucadyil, Thomas/0000-0002-2907-9889
FU Spanish Ministry of Economy and Competitiveness [BFU2012-34885]; Basque
Government [IE12-332]; Russian Foundation for Basic Research
[11-04-02087]; Russian Academy of Science; Ministry of Education and
Science of the Russian Federation [14.740.11.1409]; National Institute
of Child Health and Human Development; NIH [GM42455]
FX We are grateful to J. Rizo-Rey and P. Kuzmin for critical reading of the
manuscript. This work was in part supported by Spanish Ministry of
Economy and Competitiveness grant BFU2012-34885 (V.A.F.); the Basque
Government Program Etortek, grant IE12-332 (V.A.F); Russian Foundation
for Basic Research grant 11-04-02087 (P.V.B.); the Russian Academy of
Science program "Molecular and Cell Biology" (P.V.B. and S.A.A.); the
Ministry of Education and Science of the Russian Federation, grant
14.740.11.1409 (P.V.B.); the Intramural Program of the National
Institute of Child Health and Human Development (J.Z); and NIH grant
GM42455 (S.L.S.). Additional data are presented in the supplementary
materials.
NR 28
TC 42
Z9 43
U1 4
U2 78
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 MAR 22
PY 2013
VL 339
IS 6126
BP 1433
EP 1436
DI 10.1126/science.1233920
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 114KU
UT WOS:000316740700043
PM 23520112
ER
PT J
AU De Lay, N
Schu, DJ
Gottesman, S
AF De Lay, Nicholas
Schu, Daniel J.
Gottesman, Susan
TI Bacterial Small RNA-based Negative Regulation: Hfq and Its Accomplices
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Review
ID ESCHERICHIA-COLI HFQ; TARGET MESSENGER-RNAS; BINDING SMALL RNAS; SM-LIKE
PROTEIN; POLYNUCLEOTIDE PHOSPHORYLASE; TRANSLATIONAL INITIATION;
NONCODING RNAS; SOLUBLE-RNAS; CRUCIAL ROLE; IN-VIVO
AB A large group of bacterial small regulatory RNAs (sRNAs) use the Hfq chaperone to mediate pairing with and regulation of mRNAs. Recent findings help to clarify how Hfq acts and highlight the role of the endonuclease RNase E and its associated proteins (the degradosome) in negative regulation by these sRNAs. sRNAs frequently uncouple transcription and translation by blocking ribosome access to the mRNA, allowing other proteins access to the mRNA. As more examples of sRNA-mediated regulation are studied, more variations on how Hfq, RNase E, and other proteins collaborate to bring about sRNA-based regulation are being found.
C1 [De Lay, Nicholas; Schu, Daniel J.; Gottesman, Susan] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Gottesman, S (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM gottesms@helix.nih.gov
FU National Cancer Institute Center for Cancer Research
FX The preparation of this review was supported in whole by the National
Institutes of Health Intramural Research Program of the National Cancer
Institute Center for Cancer Research.
NR 65
TC 96
Z9 96
U1 3
U2 45
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 MAR 22
PY 2013
VL 288
IS 12
BP 7996
EP 8003
DI 10.1074/jbc.R112.441386
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 112AS
UT WOS:000316564500001
PM 23362267
ER
PT J
AU Weisfeld-Adams, JD
Mehta, L
Rucker, JC
Dembitzer, FR
Szporn, A
Lublin, FD
Introne, WJ
Bhambhani, V
Chicka, MC
Cho, C
AF Weisfeld-Adams, James D.
Mehta, Lakshmi
Rucker, Janet C.
Dembitzer, Francine R.
Szporn, Arnold
Lublin, Fred D.
Introne, Wendy J.
Bhambhani, Vikas
Chicka, Michael C.
Cho, Catherine
TI Atypical Chediak-Higashi syndrome with attenuated phenotype: three adult
siblings homozygous for a novel LYST deletion and with neurodegenerative
disease
SO ORPHANET JOURNAL OF RARE DISEASES
LA English
DT Article
DE Chediak-Higashi syndrome; LYST; Lysosomal; Amyloid; Oxidative stress;
Parkinsonism; Neurodegenerative disease
ID BONE-MARROW-TRANSPLANTATION; PERIPHERAL NEUROPATHY; DEGENERATION;
PARKINSONISM; AMYLOIDOSIS; GRISCELLI; GENOTYPE; MUTATION
AB Background: Mutations in LYST, a gene encoding a putative lysosomal trafficking protein, cause Chediak-Higashi syndrome (CHS), an autosomal recessive disorder typically characterized by infantile-onset hemophagocytic syndrome and immunodeficiency, and oculocutaneous albinism. A small number of reports of rare, attenuated forms of CHS exist, with affected individuals exhibiting progressive neurodegenerative disease beginning in early adulthood with cognitive decline, parkinsonism, features of spinocerebellar degeneration, and peripheral neuropathy, as well as subtle pigmentary abnormalities and subclinical or absent immune dysfunction.
Methods: In a consanguineous Pakistani kindred with clinical phenotypes consistent with attenuated CHS, we performed SNP array-based homozygosity mapping and whole gene sequencing of LYST.
Results: We identified three individuals homozygous for a novel six base pair in-frame deletion in LYST (c.9827_9832ATACAA), predicting the loss of asparagine and threonine residues from the LYST transcript (p.Asn3276_Thr3277del), and segregating with the phenotype in this family.
Conclusions: We further characterize the neurologic features of the attenuated form of CHS, and discuss pathophysiologic mechanisms underlying the neurodegenerative components of CHS. Attenuated CHS is phenotypically heterogenous and should be considered when young adults develop neurodegenerative disease and have pigmentary abnormalities. We briefly discuss surveillance and management of patients with CHS-related neurodegeneration.
C1 [Weisfeld-Adams, James D.; Mehta, Lakshmi] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA.
[Rucker, Janet C.; Lublin, Fred D.; Cho, Catherine] Mt Sinai Sch Med, Dept Neurol, New York, NY USA.
[Rucker, Janet C.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA.
[Dembitzer, Francine R.; Szporn, Arnold] Mt Sinai Sch Med, Dept Pathol, New York, NY USA.
[Introne, Wendy J.; Bhambhani, Vikas] NICHHD, Sect Human Biochem Genet, NIH, Bethesda, MD 20892 USA.
[Chicka, Michael C.] Prevent Genet, Marshfield, WI USA.
RP Weisfeld-Adams, JD (reprint author), Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA.
EM james.weisfeld-adams@mssm.edu
NR 26
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U1 1
U2 4
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 MAR 22
PY 2013
VL 8
AR 46
DI 10.1186/1750-1172-8-46
PG 7
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 114SQ
UT WOS:000316763200001
PM 23521865
ER
PT J
AU Hwang, IY
Hwang, KS
Park, C
Harrison, KA
Kehrl, JH
AF Hwang, Il-Young
Hwang, Kyung-Sun
Park, Chung
Harrison, Kathleen A.
Kehrl, John H.
TI Rgs13 Constrains Early B Cell Responses and Limits Germinal Center Sizes
SO PLOS ONE
LA English
DT Article
ID GENE-EXPRESSION; IMMUNE FUNCTION; LYMPH-NODES; PROTEINS;
DIFFERENTIATION; LYMPHOCYTES; MIGRATION; DESENSITIZATION;
RESPONSIVENESS; TRAFFICKING
AB Germinal centers (GCs) are microanatomic structures that develop in secondary lymphoid organs in response to antigenic stimulation. Within GCs B cells clonally expand and their immunoglobulin genes undergo class switch recombination and somatic hypermutation. Transcriptional profiling has identified a number of genes that are prominently expressed in GC B cells. Among them is Rgs13, which encodes an RGS protein with a dual function. Its canonical function is to accelerate the intrinsic GTPase activity of heterotrimeric G-protein alpha subunits at the plasma membrane, thereby limiting heterotrimeric G-protein signaling. A unique, non-canonical function of RGS13 occurs following translocation to the nucleus, where it represses CREB transcriptional activity. The functional role of RGS13 in GC B cells is unknown. To create a surrogate marker for Rgs13 expression and a loss of function mutation, we inserted a GFP coding region into the Rgs13 genomic locus. Following immunization GFP expression rapidly increased in activated B cells, persisted in GC B cells, but declined in newly generated memory B and plasma cells. Intravital microscopy of the inguinal lymph node (LN) of immunized mice revealed the rapid appearance of GFP(+) cells at LN interfollicular regions and along the T/B cell borders, and eventually within GCs. Analysis of WT, knock-in, and mixed chimeric mice indicated that RGS13 constrains extra-follicular plasma cell generation, GC size, and GC B cell numbers. Analysis of select cell cycle and GC specific genes disclosed an aberrant gene expression profile in the Rgs13 deficient GC B cells. These results indicate that RGS13, likely acting at cell membranes and in nuclei, helps coordinate key decision points during the expansion and differentiation of naive B cells.
C1 [Hwang, Il-Young; Hwang, Kyung-Sun; Park, Chung; Harrison, Kathleen A.; Kehrl, John H.] NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Kehrl, JH (reprint author), NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jkehrl@niaid.nih.gov
OI Kehrl, John/0000-0002-6526-159X
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, 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 36
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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 MAR 22
PY 2013
VL 8
IS 3
AR e60139
DI 10.1371/journal.pone.0060139
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 111VQ
UT WOS:000316549400109
PM 23533672
ER
PT J
AU Schick, UM
McDavid, A
Crane, PK
Weston, N
Ehrlich, K
Newton, KM
Wallace, R
Bookman, E
Harrison, T
Aragaki, A
Crosslin, DR
Wang, SS
Reiner, AP
Jackson, RD
Peters, U
Larson, EB
Jarvik, GP
Carlson, CS
AF Schick, Ursula M.
McDavid, Andrew
Crane, Paul K.
Weston, Noah
Ehrlich, Kelly
Newton, Katherine M.
Wallace, Robert
Bookman, Ebony
Harrison, Tabitha
Aragaki, Aaron
Crosslin, David R.
Wang, Sophia S.
Reiner, Alex P.
Jackson, Rebecca D.
Peters, Ulrike
Larson, Eric B.
Jarvik, Gail P.
Carlson, Christopher S.
TI Confirmation of the Reported Association of Clonal Chromosomal Mosaicism
with an Increased Risk of Incident Hematologic Cancer
SO PLOS ONE
LA English
DT Article
ID SPONTANEOUS-ABORTIONS; ABNORMALITIES; LEUKEMIA; MALIGNANCIES; MUTATIONS;
GENOME; BIRTH; TET2
AB Chromosomal abnormalities provide clinical utility in the diagnosis and treatment of hematologic malignancies, and may be predictive of malignant transformation in individuals without apparent clinical presentation of a hematologic cancer. In an effort to confirm previous reports of an association between clonal mosaicism and incident hematologic cancer, we applied the anomDetectBAF algorithm to call chromosomal anomalies in genotype data from previously conducted Genome Wide Association Studies (GWAS). The genotypes were initially collected from DNA derived from peripheral blood of 12,176 participants in the Group Health electronic Medical Records and Genomics study (eMERGE) and the Women's Health Initiative (WHI). We detected clonal mosaicism in 169 individuals (1.4%) and large clonal mosaic events (>2 mb) in 117 (1.0%) individuals. Though only 9.5% of clonal mosaic carriers had an incident diagnosis of hematologic cancer (multiple myeloma, myelodysplastic syndrome, lymphoma, or leukemia), the carriers had a 5.5-fold increased risk (95% CI: 3.3-9.3; p-value = 7.5 x 10(-11)) of developing these cancers subsequently. Carriers of large mosaic anomalies showed particularly pronounced risk of subsequent leukemia (HR = 19.2, 95% CI: 8.9-41.6; p-value = 7.3x10(-14)). Thus we independently confirm the association between detectable clonal mosaicism and hematologic cancer found previously in two recent publications.
C1 [Schick, Ursula M.; McDavid, Andrew; Harrison, Tabitha; Aragaki, Aaron; Reiner, Alex P.; Peters, Ulrike; Carlson, Christopher S.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Crane, Paul K.; Larson, Eric B.] Univ Washington, Dept Med, Seattle, WA USA.
[Weston, Noah; Ehrlich, Kelly; Newton, Katherine M.; Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA USA.
[Newton, Katherine M.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Wallace, Robert] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA.
[Bookman, Ebony] NHGRI, NIH, Bethesda, MD 20892 USA.
[Crosslin, David R.; Jarvik, Gail P.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Crosslin, David R.; Jarvik, Gail P.] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA.
[Wang, Sophia S.] City Hope Natl Med Ctr, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA.
[Wang, Sophia S.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
[Reiner, Alex P.; Carlson, Christopher S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol, Columbus, OH 43210 USA.
RP Carlson, CS (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
EM ccarlson@fhcrc.org
RI Crane, Paul/C-8623-2014; Jarvik, Gail/N-6476-2014;
OI Jarvik, Gail/0000-0002-6710-8708; Crane, Paul/0000-0003-4278-7465;
McDavid, Andrew/0000-0002-6581-1213
FU National Institutes of Health (NIH) [HG004610, AG06781]; National Heart,
Lung, and Blood Institute, NIH; U.S. Department of Health and Human
Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115,
32118-32119, 32122, 42107-26, 42129-32, 44221]; GARNET Collaborative
Research Group; NHGRI Genomics and Randomized Trials Network (GARNET)
[U01 HG005152]; NIH Genes, Environment and Health Initiative [GEI] [U01
HG004424]; National Cancer Institute [R25CA094880]; [U01AG06781];
[U01HG004438]; [U01CKA137088]; [R01CKA059045]
FX The initial ADPR was funded by U01AG06781 and the initial ACT study is
also funded by U01AG06781. The eMERGE study was funded by National
Institutes of Health (NIH) award HG004610, AG06781 (Group Health
Cooperative). Genotyping of eMERGE samples was funded by grant
U01HG004438. The WHI program is funded by the National Heart, Lung, and
Blood Institute, NIH, U.S. Department of Health and Human Services
through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9,
32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. The
authors thank the WHI investigators and staff for their dedication, and
the study participants for making the program possible. A full listing
of WHI investigators can be found at:
http://www.whiscience.org/publications/WHI_investigators_shortlist.pdf.
WHI GECCO colorectal cancer study was funded by U01CKA137088 and
R01CKA059045. The authors wish to acknowledge the support of the GARNET
Collaborative Research Group. Funding support for WHI-GARNET was
provided through the NHGRI Genomics and Randomized Trials Network
(GARNET) (Grant Number U01 HG005152). Assistance with phenotype
harmonization and genotype cleaning, as well as with general study
coordination, was provided by the GARNET Coordinating Center (U01
HG005157). Funding support for genotyping, which was performed at the
Broad Institute of MIT and Harvard, was provided by the NIH Genes,
Environment and Health Initiative [GEI] (U01 HG004424). Additional
support for author UMS was provided by grant R25CA094880 from the
National Cancer Institute. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 36
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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 MAR 22
PY 2013
VL 8
IS 3
AR e59823
DI 10.1371/journal.pone.0059823
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 111VQ
UT WOS:000316549400089
PM 23533652
ER
PT J
AU Kalia, J
Swartz, KJ
AF Kalia, Jeet
Swartz, Kenton J.
TI Exploring structure-function relationships between TRP and Kv channels
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DEPENDENT K+ CHANNEL; VOLTAGE SENSOR; CAPSAICIN RECEPTOR; POTASSIUM
CHANNELS; TARANTULA TOXINS; GATING-CHARGE; PORE DOMAIN; ION-CHANNEL;
CRYSTAL-STRUCTURE; HEAT ACTIVATION
AB The molecular mechanisms underlying the activation of Transient Receptor Potential (TRP) ion channels are poorly understood when compared to those of the voltage-activated potassium (Kv) channels. The architectural and pharmacological similarities between the members of these two families of channels suggest that their structure-function relationships may have common features. We explored this hypothesis by replacing previously identified domains and critical structural motifs of the membrane-spanning portions of Kv2.1 with corresponding regions of two TRP channels, TRPM8 and TRPV1. Our results show that the S3b-S4 paddle motif of Kv2.1, but not other domains, can be replaced by the analogous regions of both TRP channels without abolishing voltage-activation. In contrast, replacement of portions of TRP channels with those of Kv2.1 consistently yielded non-functional channels. Taken together, these results suggest that most structural elements within TRP channels and Kv channels are not sufficiently related to allow for the creation of hybrid channels.
C1 [Kalia, Jeet; Swartz, Kenton J.] NINDS, Porter Neurosci Res Ctr, Mol Physiol & Biophys Sect, NIH, Bethesda, MD 20892 USA.
RP Swartz, KJ (reprint author), NINDS, Porter Neurosci Res Ctr, Mol Physiol & Biophys Sect, NIH, 35 Convent Dr, Bethesda, MD 20892 USA.
EM swartzk@ninds.nih.gov
FU Intramural Research Program of the National Institutes of Health
National Institute of Neurological Disorders and Stroke; National
Institutes of Health National Institute of Neurological Disorders and
Stroke competitive fellowship
FX We thank Miguel Holmgren, Andres Jara-Oseguera, Dmitriy Krepkiy, Mark
Mayer, Joe Mindell and members of the Swartz lab for helpful
discussions. This work was supported by the Intramural Research Program
of the National Institutes of Health National Institute of Neurological
Disorders and Stroke (to K.J.S.), and by a National Institutes of Health
National Institute of Neurological Disorders and Stroke competitive
fellowship (to J.K.).
NR 59
TC 17
Z9 17
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD MAR 22
PY 2013
VL 3
AR 1523
DI 10.1038/srep01523
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 111TT
UT WOS:000316544400006
PM 23519328
ER
PT J
AU Kubler-Kielb, J
Vinogradov, E
Ng, WI
Maczynska, B
Junka, A
Bartoszewicz, M
Zelazny, A
Bennett, J
Schneerson, R
AF Kubler-Kielb, Joanna
Vinogradov, Evgeny
Ng, Weng-Ian
Maczynska, Beata
Junka, Adam
Bartoszewicz, Marzenna
Zelazny, Adrian
Bennett, John
Schneerson, Rachel
TI The capsular polysaccharide and lipopolysaccharide structures of two
carbapenem resistant Klebsiella pneumoniae outbreak isolates
SO CARBOHYDRATE RESEARCH
LA English
DT Article
DE Capsular polysaccharide; LPS; Structure; KPC; CRKP
ID VACCINE; IMMUNOGENICITY; SEROTYPES; ANTIGENS; STRAINS
AB Carbapenem resistant Klebsiella pneumoniae (CRKP) are isolated with increasing frequency, especially from immunocompromized patients. The capsular polysaccharide (CPS) types of CPKP were not determined. Investigation of two CRKP isolates from a 2011 outbreak at the Clinical Center, the National Institutes of Health, identified a new capsular type shared by the two isolates, similar to K. pneumonia K19 and K34 but structurally different than any published K. pneumoniae CPS repeating unit:
-[-2-alpha-L-Rha-2-alpha-L-Rha-2-alpha-L-Rha-3-beta-D-Gal-3-alpha-D-GalA-](n)- vertical bar 4 alpha-L-Rha
The LPS of the two isolates was found to have no O-specific polysaccharide and the chemical structure of the core oligosaccharides agreed with the published data.
If this structure type will be prevalent among CPKP isolates, our findings could facilitate rapid diagnosis and help to develop new therapeutic solutions to this antibiotic resistant pathogen. Published by Elsevier Ltd.
C1 [Kubler-Kielb, Joanna; Ng, Weng-Ian; Schneerson, Rachel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev & Mol Immun, NIH, Bethesda, MD 20892 USA.
[Vinogradov, Evgeny] Natl Res Council Canada, Ottawa, ON K1A 0R6, Canada.
[Maczynska, Beata; Junka, Adam; Bartoszewicz, Marzenna] Med Acad Wroclaw, Dept Microbiol, Wroclaw, Poland.
[Zelazny, Adrian] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Bennett, John] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Kubler-Kielb, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev & Mol Immun, NIH, Bethesda, MD 20892 USA.
EM kielbj@mail.nih.gov
OI Vinogradov, Evgeny/0000-0002-5364-1376
FU NICHD; NIAID; Clinical Center, National Institutes of Health, Bethesda,
MD
FX Authors thank Prof. A. Przondo-Mordarska and Prof. A. Gamian for help in
this project. This work was partially supported by the intramural
programs of NICHD, NIAID and Clinical Center, National Institutes of
Health, Bethesda, MD.
NR 25
TC 6
Z9 6
U1 3
U2 24
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0008-6215
J9 CARBOHYD RES
JI Carbohydr. Res.
PD MAR 22
PY 2013
VL 369
BP 6
EP 9
DI 10.1016/j.carres.2012.12.018
PG 4
WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 102CM
UT WOS:000315821000003
PM 23360863
ER
PT J
AU Ladell, K
Hashimoto, M
Iglesias, MC
Wilmann, PG
McLaren, JE
Gras, S
Chikata, T
Kuse, N
Fastenackels, S
Gostick, E
Bridgeman, JS
Venturi, V
Arkoub, ZA
Agut, H
van Bockel, DJ
Almeida, JR
Douek, DC
Meyer, L
Venet, A
Takiguchi, M
Rossjohn, J
Price, DA
Appay, V
AF Ladell, Kristin
Hashimoto, Masao
Iglesias, Maria Candela
Wilmann, Pascal G.
McLaren, James E.
Gras, Stephanie
Chikata, Takayuki
Kuse, Nozomi
Fastenackels, Solene
Gostick, Emma
Bridgeman, John S.
Venturi, Vanessa
Arkoub, Zaina Ait
Agut, Henri
van Bockel, David J.
Almeida, Jorge R.
Douek, Daniel C.
Meyer, Laurence
Venet, Alain
Takiguchi, Masafumi
Rossjohn, Jamie
Price, David A.
Appay, Victor
TI A Molecular Basis for the Control of Preimmune Escape Variants by
HIV-Specific CD8(+) T Cells
SO IMMUNITY
LA English
DT Article
ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I; LYMPHOCYTE ESCAPE; ANTIGEN
RECOGNITION; INFECTION; RESPONSES; TYPE-1; GAG; DIVERSITY; REPLICATION
AB The capacity of the immune system to adapt to rapidly evolving viruses is a primary feature of effective immunity, yet its molecular basis is unclear. Here, we investigated protective HIV-1-specific CD8(+) T cell responses directed against the immunodominant p24 Gag-derived epitope KK10 (KRWIILGLNK(263-272)) presented by human leukocyte antigen (HLA)-B*2705. We found that cross-reactive CD8(+) T cell clonotypes were mobilized to counter the rapid emergence of HIV-1 variants that can directly affect T cell receptor (TCR) recognition. These newly recruited clonotypes expressed TCRs that engaged wild-type and mutant KK10 antigens with similar affinities and almost identical docking modes, thereby accounting for their antiviral efficacy in HLA-B*2705(+) individuals. A protective CD8(+) T cell repertoire therefore encompasses the capacity to control TCR-accessible mutations, ultimately driving the development of more complex viral escape variants that disrupt antigen presentation.
C1 [Ladell, Kristin; McLaren, James E.; Gostick, Emma; Bridgeman, John S.; Rossjohn, Jamie; Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales.
[Hashimoto, Masao; Chikata, Takayuki; Kuse, Nozomi; Takiguchi, Masafumi] Kumamoto Univ, Ctr AIDS Res, Kumamoto 8600811, Japan.
[Iglesias, Maria Candela; Fastenackels, Solene; Almeida, Jorge R.; Appay, Victor] Univ Paris 06, Hop La Pitie Salpetriere, INSERM UMR S 945, F-75013 Paris, France.
[Wilmann, Pascal G.; Gras, Stephanie; Rossjohn, Jamie] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
[Venturi, Vanessa] Univ New S Wales, Ctr Vasc Res, Computat Biol Grp, Sydney, NSW 2052, Australia.
[Arkoub, Zaina Ait; Agut, Henri] Univ Paris 06, Hop La Pitie Salpetriere, DETIV UPMC ER1, Virol Lab, F-75013 Paris, France.
[van Bockel, David J.] St Vincents Ctr Appl Med Res, Sydney, NSW 2010, Australia.
[van Bockel, David J.] Univ New S Wales, Sydney, NSW 2010, Australia.
[Almeida, Jorge R.; Douek, Daniel C.; Price, David A.] NIAID, Vaccine Res Ctr, Human Immunol Sect, NIH, Bethesda, MD 20892 USA.
[Meyer, Laurence; Venet, Alain] Univ Paris 11, Hop Kremlin Bicetre, INSERM, F-94275 Le Kremlin Bicetre, France.
[Appay, Victor] Grp Hosp Pitie Salpetriere, AP HP, Lab Immunol Cellulaire & Tissulaire, F-75013 Paris, France.
RP Appay, V (reprint author), Univ Paris 06, Hop La Pitie Salpetriere, INSERM UMR S 945, F-75013 Paris, France.
EM victor.appay@upmc.fr
RI Rossjohn, Jamie/F-9032-2013; Ladell, Kristin/K-2475-2013; Price,
David/C-7876-2013; Ladell, Kristin/C-8301-2013; Takiguchi,
Masafumi/E-7468-2013;
OI Rossjohn, Jamie/0000-0002-2020-7522; Price, David/0000-0001-9416-2737;
Ladell, Kristin/0000-0002-9856-2938; Ramos de Almeida,
Jorge/0000-0002-5009-8478
FU ANR, Sidaction [ANR-09-JCJC-0114-01]; French ANRS; National Institutes
of Health via the Intramural Program of the Vaccine Research Center
(National Institute of Allergy and Infectious Diseases); Australian
Research Council (ARC); Australian National Health and Medical Research
Council (NHMRC); UK Biotechnology and Biological Sciences Research
Council [BB/H001085/1]; Japanese Ministry of Health [18390141]; Global
COE program ("Global Education and Research Center Aiming at the Control
of AIDS'') of the Japanese Ministry of Education, Science, Sports, and
Culture; Sidaction Fellowship
FX We thank all study participants, the French Agence Nationale de la
Recherche sur le SIDA (ANRS) Cohorts ALT and PRIMO groups, and the staff
at the MX2 beamline (Australian synchrotron). We are grateful to C.
Blanc for sorting viable infected cells at the Pitie-Salpetriere Flow
Cytometry Platform. This work was supported by the ANR (project
ANR-09-JCJC-0114-01), Sidaction, the French ANRS, the National
Institutes of Health via the Intramural Program of the Vaccine Research
Center (National Institute of Allergy and Infectious Diseases), the
Australian Research Council (ARC), the Australian National Health and
Medical Research Council (NHMRC), the UK Biotechnology and Biological
Sciences Research Council (grant BB/H001085/1), the Japanese Ministry of
Health (grant 18390141), and the Global COE program ("Global Education
and Research Center Aiming at the Control of AIDS'') of the Japanese
Ministry of Education, Science, Sports, and Culture. M. C. I. is
supported by a Sidaction Fellowship. V. V. and S. G. are ARC Future
Fellows. P. G. W. is an NHMRC CJ Martin Fellow. J.R. is an NHMRC
Australia Fellow. D. A. P. is a Wellcome Trust Senior Investigator.
NR 48
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Z9 69
U1 2
U2 14
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 MAR 21
PY 2013
VL 38
IS 3
BP 425
EP 436
DI 10.1016/j.immuni.2012.11.021
PG 12
WC Immunology
SC Immunology
GA AA2RJ
UT WOS:000330941500009
PM 23521884
ER
PT J
AU Mattila, PK
Feest, C
Depoil, D
Treanor, B
Montaner, B
Otipoby, KL
Carter, R
Justement, LB
Bruckbauer, A
Batista, FD
AF Mattila, Pieta K.
Feest, Christoph
Depoil, David
Treanor, Bebhinn
Montaner, Beatriz
Otipoby, Kevin L.
Carter, Robert
Justement, Louis B.
Bruckbauer, Andreas
Batista, Facundo D.
TI The Actin and Tetraspanin Networks Organize Receptor Nanoclusters to
Regulate B Cell Receptor-Mediated Signaling
SO IMMUNITY
LA English
DT Article
ID IMMUNE-SYNAPSE FORMATION; ANTIGEN RECEPTOR; MICROCLUSTER FORMATION;
LYMPHOCYTE DEVELOPMENT; MEMBRANE; MICE; ACTIVATION; RESPONSES;
TRANSDUCTION; EXPRESSION
AB A key role is emerging for the cytoskeleton in coordinating receptor signaling, although the underlying molecular requirements remain unclear. Here we show that cytoskeleton disruption triggered signaling requiring not only the B cell receptor (BCR), but also the coreceptor CD19 and tetraspanin CD81, thus providing a mechanism for signal amplification upon surface-bound antigen stimulation. By using superresolution microscopy, we demonstrated that endogenous IgM, IgD, and CD19 exhibited distinct nanoscale organization within the plasma membrane of primary B cells. Upon stimulation, we detect a local convergence of receptors, although their global organization was not dramatically altered. Thus, we postulate that cytoskeleton reorganization releases BCR nanoclusters, which can interact with CD19 held in place by the tetraspanin network. These results not only suggest that receptor compartmentalization regulates antigen-induced activation but also imply a potential role for CD19 in mediating ligand-independent "tonic'' BCR signaling necessary for B cell survival.
C1 [Mattila, Pieta K.; Feest, Christoph; Depoil, David; Treanor, Bebhinn; Montaner, Beatriz; Bruckbauer, Andreas; Batista, Facundo D.] Canc Res UK, London Res Inst, Lymphocyte Interact Lab, London WC2A 3LY, England.
[Otipoby, Kevin L.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Otipoby, Kevin L.] Immune Dis Inst, Boston, MA 02115 USA.
[Carter, Robert] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Justement, Louis B.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
RP Batista, FD (reprint author), Canc Res UK, London Res Inst, Lymphocyte Interact Lab, 44 Lincolns Inn Fields, London WC2A 3LY, England.
EM facundo.batista@cancer.org.uk
RI Mattila, Pieta/G-6815-2013; Feest, Christoph/C-7874-2013;
OI Mattila, Pieta/0000-0003-2805-0686; Feest,
Christoph/0000-0002-0772-7267; Justement, Louis/0000-0001-7058-867X
FU Cancer Research UK; Royal Society Wolfson Research Merit Award; Human
Frontier Science Program
FX We are extremely thankful to K. Rajewsky, K. Okkenhaug, and S. Levy for
providing B1-8f Igh, Cd21-cre, E mu-Bcl2 transgenic, PI3K delta-mutant,
and CD81-deficient mice, respectively. We would also like to thank D.
Bray and members of the Lymphocyte Interaction Laboratory for critically
reading the manuscript and for helpful discussions and comments. This
work was supported by Cancer Research UK, Royal Society Wolfson Research
Merit Award (F. D. B.), and Human Frontier Science Program (P.K.M.).
NR 43
TC 97
Z9 99
U1 1
U2 15
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 MAR 21
PY 2013
VL 38
IS 3
BP 461
EP 474
DI 10.1016/j.immuni.2012.11.019
PG 14
WC Immunology
SC Immunology
GA AA2RJ
UT WOS:000330941500012
PM 23499492
ER
PT J
AU Kastenmuller, W
Brandes, M
Wang, Z
Herz, J
Egen, JG
Germain, RN
AF Kastenmueller, Wolfgang
Brandes, Marlene
Wang, Ze
Herz, Jasmin
Egen, Jackson G.
Germain, Ronald N.
TI Peripheral Prepositioning and Local CXCL9 Chemokine-Mediated Guidance
Orchestrate Rapid Memory CD8(+) T Cell Responses in the Lymph Node
SO IMMUNITY
LA English
DT Article
ID CLASSICAL DENDRITIC CELLS; ANTIGEN-PRESENTING CELL;
HERPES-SIMPLEX-VIRUS; RECALL RESPONSES; COGNATE ANTIGEN; RECEPTOR CXCR3;
CD8+T CELLS; IN-VIVO; B-CELLS; INFECTION
AB After an infection, the immune system generates long-lived memory lymphocytes whose increased frequency and altered state of differentiation enhance host defense against reinfection. Recently, the spatial distribution of memory cells was found to contribute to their protective function. Effector memory CD8(+) T cells reside in peripheral tissue sites of initial pathogen encounter, in apparent anticipation of reinfection. Here we show that within lymph nodes (LNs), memory CD8(+) T cells were concentrated near peripheral entry portals of lymph-borne pathogens, promoting rapid engagement of infected sentinel macrophages. A feed-forward CXCL9-dependent circuit provided additional chemotactic cues that further increase local memory cell density. Memory CD8(+) T cells also produced effector responses to local cytokine triggers, but their dynamic behavior differed from that seen after antigen recognition. These data reveal the distinct localization and dynamic behavior of naive versus memory T cells within LNs and how these differences contribute to host defense.
C1 [Kastenmueller, Wolfgang; Brandes, Marlene; Wang, Ze; Egen, Jackson G.; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Herz, Jasmin] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
[Egen, Jackson G.] Genentech Res & Early Dev, Dept Immunol, San Francisco, CA 94080 USA.
RP Kastenmuller, W (reprint author), Univ Bonn, Inst Mol Med, D-53105 Bonn, Germany.
EM wkastenm@uni-bonn.de; rgermain@nih.gov
OI Egen, Jackson/0000-0003-2053-0837
FU Intramural Research Program, NIAID, NIH; DFG [KA 3091/1-1, HE 6068/1-1]
FX We would like to thank J. Farber and A. Luster for providing critical
reagents, M. Gerner for help with imaging analysis, and G. Gasteiger, T.
Lammermann, and N. van Panhuys for critically reading the manuscript. We
are especially grateful to A. Luster and U. von Andrian for generously
sharing unpublished data while this study was in progress or in
revision. MVA NP-S-GFP was kindly provided by I. Drexler. This research
was supported by the Intramural Research Program, NIAID, NIH, by DFG, KA
3091/1-1 to W. K., and HE 6068/1-1 to J.H.
NR 58
TC 63
Z9 63
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 MAR 21
PY 2013
VL 38
IS 3
BP 502
EP 513
DI 10.1016/j.immuni.2012.11.012
PG 12
WC Immunology
SC Immunology
GA AA2RJ
UT WOS:000330941500015
PM 23352234
ER
PT J
AU Wan, CK
Oh, J
Li, P
West, EE
Wong, EA
Andraski, AB
Spolski, R
Yu, ZX
He, JP
Kelsall, BL
Leonard, WJ
AF Wan, Chi-Keung
Oh, Jangsuk
Li, Peng
West, Erin E.
Wong, Elizabeth A.
Andraski, Allison B.
Spolski, Rosanne
Yu, Zu-Xi
He, Jianping
Kelsall, Brian L.
Leonard, Warren J.
TI The Cytokines IL-21 and GM-CSF Have Opposing Regulatory Roles in the
Apoptosis of Conventional Dendritic Cells
SO IMMUNITY
LA English
DT Article
ID FOLLICULAR-HELPER-CELLS; HUMAN B-CELLS; T-CELLS; NEGATIVE REGULATOR;
IMMUNE TOLERANCE; STEADY-STATE; NKT CELLS; INTERLEUKIN-21;
DIFFERENTIATION; HOMEOSTASIS
AB Interleukin-21 (IL-21) has broad actions on T and B cells, but its actions in innate immunity are poorly understood. Here we show that IL-21 induced apoptosis of conventional dendritic cells (cDCs) via STAT3 and Bim, and this was inhibited by granulocyte-macrophage colony-stimulating factor (GM-CSF). ChIP-Seq analysis revealed genome-wide binding competition between GM-CSF-induced STAT5 and IL-21-induced STAT3. Expression of IL-21 in vivo decreased cDC numbers, and this was prevented by GM-CSF. Moreover, repetitive alpha-galactosylceramide injection of mice induced IL-21 but decreased GM-CSF production by natural killer T (NKT) cells, correlating with decreased cDC numbers. Furthermore, adoptive transfer of wild-type CD4(+) T cells caused more severe colitis with increased DCs and interferon-gamma (IFN-gamma)-producing CD4(+) T cells in Il21r(-/-)Rag2(-/-) mice (which lack T cells and have IL-21-unresponsive DCs) than in Rag2(-/-) mice. Thus, IL-21 and GM-CSF exhibit cross-regulatory actions on gene regulation and apoptosis, regulating cDC numbers and thereby the magnitude of the immune response.
C1 [Wan, Chi-Keung; Oh, Jangsuk; Li, Peng; West, Erin E.; Wong, Elizabeth A.; Andraski, Allison B.; Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Wan, Chi-Keung; Oh, Jangsuk; Li, Peng; West, Erin E.; Wong, Elizabeth A.; Andraski, Allison B.; Spolski, Rosanne; Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA.
[Yu, Zu-Xi] NHLBI, Pathol Core, NIH, Bethesda, MD 20892 USA.
[He, Jianping; Kelsall, Brian L.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM wjl@helix.nih.gov
FU Intramural Research Program, National Heart, Lung, and Blood Institute,
NIH
FX We thank J.X. Lin, NHLBI and R. Schwartz, NIAID, for critical comments,
H. Young for the Csf2 and control expression plasmids, L. Hennighausen
and G. Robinson for Stat5a-/- mice, and NHLBI Flow Cytometry
Core Facility for cell sorting and sample analysis. This work was
supported by the Intramural Research Program, National Heart, Lung, and
Blood Institute, NIH. R.S. and W.J.L. are inventors on patents related
to IL-21.
NR 59
TC 42
Z9 44
U1 0
U2 6
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 MAR 21
PY 2013
VL 38
IS 3
BP 514
EP 527
DI 10.1016/j.immuni.2013.02.011
PG 14
WC Immunology
SC Immunology
GA AA2RJ
UT WOS:000330941500016
PM 23453633
ER
PT J
AU Blakey, DH
Lafontaine, M
Lavigne, J
Sokolowski, D
Philippe, JM
Sapori, JM
Biederbick, W
Horre, R
Marzi, WB
Kondo, H
Kuroki, Y
Namera, A
Okumura, T
Yamamoto, M
Yashiki, M
Blain, PG
Russell, DR
Cibulsky, SM
Jett, DA
AF Blakey, David H.
Lafontaine, Marc
Lavigne, Jocelyn
Sokolowski, Danny
Philippe, Jean-Marc
Sapori, Jean-Marc
Biederbick, Walter
Horre, Regine
Marzi, Willi B.
Kondo, Hisayoshi
Kuroki, Yumiko
Namera, Akira
Okumura, Tetsu
Yamamoto, Miyako
Yashiki, Mikio
Blain, Peter G.
Russell, David R.
Cibulsky, Susan M.
Jett, David A.
CA Global Hlth Security Initiative
TI A screening tool to prioritize public health risk associated with
accidental or deliberate release of chemicals into the atmosphere
SO BMC PUBLIC HEALTH
LA English
DT Article
DE Chemicals; Public health; Risk assessment; Atmospheric releases;
Screening tool; Disaster management cycle
AB The Chemical Events Working Group of the Global Health Security Initiative has developed a flexible screening tool for chemicals that present a risk when accidentally or deliberately released into the atmosphere. The tool is generic, semi-quantitative, independent of site, situation and scenario, encompasses all chemical hazards (toxicity, flammability and reactivity), and can be easily and quickly implemented by non-subject matter experts using freely available, authoritative information. Public health practitioners and planners can use the screening tool to assist them in directing their activities in each of the five stages of the disaster management cycle.
C1 [Blakey, David H.; Lafontaine, Marc; Lavigne, Jocelyn; Sokolowski, Danny; Philippe, Jean-Marc; Sapori, Jean-Marc; Biederbick, Walter; Horre, Regine; Marzi, Willi B.; Kondo, Hisayoshi; Kuroki, Yumiko; Namera, Akira; Okumura, Tetsu; Yamamoto, Miyako; Yashiki, Mikio; Blain, Peter G.; Russell, David R.; Cibulsky, Susan M.; Jett, David A.] Global Hlth Secur Initiat, Chem Events Working Grp, Cardiff CF5 2YB, S Glam, Wales.
[Blakey, David H.] Hlth Canada, Environm Hlth Sci & Res Bur, Ottawa, ON K1A 0L2, Canada.
[Lafontaine, Marc; Lavigne, Jocelyn; Sokolowski, Danny] Hlth Canada, Chem Emergency Preparedness & Response Unit, Ottawa, ON K1A 0L2, Canada.
[Philippe, Jean-Marc] Hosp Civils Lyon, Poison Control Ctr, Ctr Antipoison, Lyon, France.
[Biederbick, Walter] Robert Koch Inst, Ctr Biol Secur, Berlin, Germany.
[Biederbick, Walter; Horre, Regine] Fed Off Civil Protect & Disaster Assistance, Bonn, Germany.
[Marzi, Willi B.] Fed Minist Interior, Bonn, Germany.
[Kondo, Hisayoshi] Natl Disaster Med Ctr, MHLW DMAT Bur, Tokyo, Japan.
[Kuroki, Yumiko] Japan Poison Informat Ctr, Tsukuba Off, Tsukuba, Ibaraki, Japan.
[Namera, Akira; Yashiki, Mikio] Hiroshima Univ, Hiroshima, Japan.
[Okumura, Tetsu] Govt Japan, Off Assistant Chief Cabinet Secretary Natl Secur, Cabinet Secretariat, Tokyo, Japan.
[Yamamoto, Miyako] Natl Inst Hlth Sci, Div Safety Informat Drug Food & Chem, Setagaya Ku, Tokyo, Japan.
[Blain, Peter G.] Newcastle Univ, Med Toxicol Ctr, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Russell, David R.] Cardiff Metropolitan Univ, WHO Collaborating Ctr Chem Incidents, Hlth Protect Agcy, Cardiff CF5 2YB, S Glam, Wales.
[Cibulsky, Susan M.] Off Assistant Secretary Preparedness & Response, Hlth Serv, Washington, DC USA.
[Cibulsky, Susan M.] Off Assistant Secretary Preparedness & Response, Human Serv, Washington, DC USA.
[Jett, David A.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Russell, DR (reprint author), Global Hlth Secur Initiat, Chem Events Working Grp, Cardiff CF5 2YB, S Glam, Wales.
EM david.russell@hpa.org.uk
NR 36
TC 3
Z9 3
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD MAR 21
PY 2013
VL 13
AR 253
DI 10.1186/1471-2458-13-253
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 207AR
UT WOS:000323569300001
PM 23517410
ER
PT J
AU Wu, SP
Minter, A
Costello, R
Zingone, A
Lee, CK
Au, WY
Landgren, O
AF Wu, S. Peter
Minter, Alex
Costello, Rene
Zingone, Adriana
Lee, Cheuk-Kwong
Au, Wing-Yan
Landgren, Ola
TI MGUS prevalence in an ethnically Chinese population in Hong Kong
SO BLOOD
LA English
DT Letter
ID UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; MULTIPLE-MYELOMA
C1 [Wu, S. Peter; Minter, Alex; Costello, Rene; Zingone, Adriana; Landgren, Ola] NCI, Multiple Myeloma Sect, Metab Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Cheuk-Kwong] Hong Kong Red Cross Blood Transfus Serv, Hong Kong, Hong Kong, Peoples R China.
[Au, Wing-Yan] Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China.
RP Landgren, O (reprint author), NCI, Multiple Myeloma Sect, Metab Branch, NIH, 9000 Rockville Pike,Bldg 10 Room 13N240, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
FU Intramural NIH HHS
NR 8
TC 6
Z9 6
U1 0
U2 0
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 MAR 21
PY 2013
VL 121
IS 12
BP 2363
EP 2364
DI 10.1182/blood-2012-11-466011
PG 2
WC Hematology
SC Hematology
GA 182RI
UT WOS:000321761100028
PM 23520330
ER
PT J
AU Klion, AD
Mejia, R
Cowen, EW
Dowdell, KC
Dunleavy, K
Fahle, GA
Holland-Thomas, N
Maric, I
Pittaluga, S
Raffeld, M
Santos, C
Steller-Stevenson, M
Krogmann, T
Shatzer, AN
Turk, SP
Yin, YZ
Xi, LQ
Prussin, C
Cohen, JI
AF Klion, Amy D.
Mejia, Rojelio
Cowen, Edward W.
Dowdell, Kennichi C.
Dunleavy, Kieron
Fahle, Gary A.
Holland-Thomas, Nicole
Maric, Irina
Pittaluga, Stefania
Raffeld, Mark
Santos, Carlo
Steller-Stevenson, Maryalice
Krogmann, Tammy
Shatzer, Amber N.
Turk, Siu-Ping
Yin, Yuzhi
Xi, Liqiang
Prussin, Calman
Cohen, Jeffrey I.
TI Chronic active Epstein-Barr virus infection: a novel cause of
lymphocytic variant hypereosinophilic syndrome
SO BLOOD
LA English
DT Letter
C1 [Klion, Amy D.; Mejia, Rojelio; Santos, Carlo] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
[Dowdell, Kennichi C.; Krogmann, Tammy; Shatzer, Amber N.; Cohen, Jeffrey I.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Dunleavy, Kieron] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
[Fahle, Gary A.; Maric, Irina] NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Holland-Thomas, Nicole] NCI, Parasit Dis Lab, Clin Res Directorate, Clin Monitoring Res Program,SAIC Frederick Inc,Fr, Frederick, MD 21701 USA.
[Pittaluga, Stefania; Raffeld, Mark; Steller-Stevenson, Maryalice; Xi, Liqiang] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Turk, Siu-Ping] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Yin, Yuzhi; Prussin, Calman] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Klion, AD (reprint author), NIH, Bldg 4,Room B1-28,4 Mem Dr, Bethesda, MD 20892 USA.
EM aklion@nih.gov
OI Prussin, Calman/0000-0002-3917-3326; Klion, Amy/0000-0002-4986-5326
FU Intramural NIH HHS
NR 4
TC 7
Z9 9
U1 1
U2 4
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 MAR 21
PY 2013
VL 121
IS 12
BP 2364
EP 2366
DI 10.1182/blood-2012-12-472720
PG 5
WC Hematology
SC Hematology
GA 182RI
UT WOS:000321761100029
PM 23520331
ER
PT J
AU Friboulet, L
Olaussen, KA
Pignon, JP
Shepherd, FA
Tsao, MS
Graziano, S
Kratzke, R
Douillard, JY
Seymour, L
Pirker, R
Filipits, M
Andre, F
Solary, E
Ponsonnailles, F
Robin, A
Stoclin, A
Dorvault, N
Commo, F
Adam, J
Vanhecke, E
Saulnier, P
Thomale, J
Le Chevalier, T
Dunant, A
Rousseau, V
Le Teuff, G
Brambilla, E
Soria, JC
AF Friboulet, Luc
Olaussen, Ken Andre
Pignon, Jean-Pierre
Shepherd, Frances A.
Tsao, Ming-Sound
Graziano, Stephen
Kratzke, Robert
Douillard, Jean-Yves
Seymour, Lesley
Pirker, Robert
Filipits, Martin
Andre, Fabrice
Solary, Eric
Ponsonnailles, Florence
Robin, Angelique
Stoclin, Annabelle
Dorvault, Nicolas
Commo, Frederic
Adam, Julien
Vanhecke, Elsa
Saulnier, Patrick
Thomale, Juergen
Le Chevalier, Thierry
Dunant, Ariane
Rousseau, Vanessa
Le Teuff, Gwenael
Brambilla, Elisabeth
Soria, Jean-Charles
TI ERCC1 Isoform Expression and DNA Repair in Non-Small-Cell Lung Cancer
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID III BETA-TUBULIN; MESSENGER-RNA EXPRESSION; COMPLEMENTATION GROUP 1;
ADJUVANT CHEMOTHERAPY; MONOCLONAL-ANTIBODIES; SURVIVAL; TRIAL;
IMMUNODETECTION; VALIDATION; CARCINOMA
AB Background
The excision repair cross-complementation group 1 (ERCC1) protein is a potential prognostic biomarker of the efficacy of cisplatin-based chemotherapy in non-small-cell lung cancer (NSCLC). Although several ongoing trials are evaluating the level of expression of ERCC1, no consensus has been reached regarding a method for evaluation.
Methods
We used the 8F1 antibody to measure the level of expression of ERCC1 protein by means of immunohistochemical analysis in a validation set of samples obtained from 494 patients in two independent phase 3 trials (the National Cancer Institute of Canada Clinical Trials Group JBR. 10 and the Cancer and Leukemia Group B 9633 trial from the Lung Adjuvant Cisplatin Evaluation Biology project). We compared the results of repeated staining of the entire original set of samples obtained from 589 patients in the International Adjuvant Lung Cancer Trial Biology study, which had led to the initial correlation between the absence of ERCC1 expression and platinum response, with our previous results in the same tumors. We mapped the epitope recognized by 16 commercially available ERCC1 antibodies and investigated the capacity of the different ERCC1 isoforms to repair platinum-induced DNA damage.
Results
We were unable to validate the predictive effect of immunostaining for ERCC1 protein. The discordance in the results of staining for ERCC1 suggested a change in the performance of the 8F1 antibody since 2006. We found that none of the 16 antibodies could distinguish among the four ERCC1 protein isoforms, whereas only one isoform produced a protein that had full capacities for nucleotide excision repair and cisplatin resistance.
Conclusions Immunohistochemical analysis with the use of currently available ERCC1 antibodies did not specifically detect the unique functional ERCC1 isoform. As a result, its usefulness in guiding therapeutic decision making is limited. (Funded by Eli Lilly and others.)
C1 [Friboulet, Luc; Olaussen, Ken Andre; Andre, Fabrice; Ponsonnailles, Florence; Robin, Angelique; Stoclin, Annabelle; Dorvault, Nicolas; Commo, Frederic; Adam, Julien; Vanhecke, Elsa; Soria, Jean-Charles] Inst Gustave Roussy, INSERM, U981, F-94805 Villejuif, France.
[Friboulet, Luc; Olaussen, Ken Andre; Ponsonnailles, Florence; Robin, Angelique; Stoclin, Annabelle; Dorvault, Nicolas; Commo, Frederic; Adam, Julien; Vanhecke, Elsa; Soria, Jean-Charles] Inst Gustave Roussy, Dept Hosp Univ Thorax Innovat, F-94805 Villejuif, France.
[Andre, Fabrice; Le Chevalier, Thierry; Soria, Jean-Charles] Inst Gustave Roussy, Dept Canc Med, F-94805 Villejuif, France.
[Pignon, Jean-Pierre; Dunant, Ariane; Rousseau, Vanessa; Le Teuff, Gwenael] Inst Gustave Roussy, Biostat & Epidemiol Unit, F-94805 Villejuif, France.
[Solary, Eric] Inst Gustave Roussy, INSERM, UMR1009, F-94805 Villejuif, France.
[Saulnier, Patrick] Inst Gustave Roussy, Translat Res Unit, F-94805 Villejuif, France.
[Friboulet, Luc; Olaussen, Ken Andre; Andre, Fabrice; Solary, Eric; Ponsonnailles, Florence; Robin, Angelique; Stoclin, Annabelle; Dorvault, Nicolas; Commo, Frederic; Adam, Julien; Vanhecke, Elsa; Le Chevalier, Thierry; Soria, Jean-Charles] Univ Paris 11, Le Kremlin Bicetre, France.
[Douillard, Jean-Yves] Inst Canc Ouest Rene Gauducheau, Nantes, France.
[Brambilla, Elisabeth] Univ Grenoble 1, CHU Grenoble, Hop Albert Michallon, Inst Albert Bonniot,Dept Pathol,INSERM,U823, Grenoble, France.
[Shepherd, Frances A.] Univ Hlth Network, Princess Margaret Hosp, Dept Med, Toronto, ON, Canada.
[Tsao, Ming-Sound] Univ Hlth Network, Princess Margaret Hosp, Dept Pathol, Toronto, ON, Canada.
[Graziano, Stephen] SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA.
[Kratzke, Robert] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Seymour, Lesley] Canada Clin Trials Grp, NCI, Kingston, ON, Canada.
[Pirker, Robert; Filipits, Martin] Med Univ Vienna, Dept Med 1, Vienna, Austria.
[Thomale, Juergen] Univ Duisburg Essen Med Sch, Inst Cell Biol, Essen, Germany.
RP Soria, JC (reprint author), Inst Gustave Roussy, INSERM, U981, 114 Rue Edouard Vaillant, F-94805 Villejuif, France.
EM soria@igr.fr
RI Brambilla, Elisabeth/L-8796-2013; friboulet, luc/N-7276-2015
OI friboulet, luc/0000-0002-1129-4978
FU Eli Lilly; Institut National du Cancer Programme National d'Excellence
Specialise and Programme Hospitalier de Recherche Clinique; La Ligue
Nationale contre le Cancer; Sanofi-Aventis; European Union
[HEALTH-F2-2010-258677-CURELUNG]; Roche
FX Supported by an unrestricted grant from Eli Lilly and by grants from
Institut National du Cancer Programme National d'Excellence Specialise
and Programme Hospitalier de Recherche Clinique (to the International
Adjuvant Lung Cancer Trial Biology); by La Ligue Nationale contre le
Cancer and an unrestricted grant from Sanofi-Aventis (to the Lung
Adjuvant Cisplatin Evaluation Biology project); by a contract
(FP7-2007-13) from the European Union Seventh Framework Program under a
grant agreement (HEALTH-F2-2010-258677-CURELUNG); and by a translational
research fellowship from Roche (to Dr. Friboulet).
NR 39
TC 148
Z9 161
U1 2
U2 38
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 21
PY 2013
VL 368
IS 12
BP 1101
EP 1110
DI 10.1056/oa1214271
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 108TH
UT WOS:000316318600003
PM 23514287
ER
PT J
AU Freudlsperger, C
Bian, Y
Wise, SC
Burnett, J
Coupar, J
Yang, X
Chen, Z
Van Waes, C
AF Freudlsperger, C.
Bian, Y.
Wise, S. Contag
Burnett, J.
Coupar, J.
Yang, X.
Chen, Z.
Van Waes, C.
TI TGF-beta and NF-kappa B signal pathway cross-talk is mediated through
TAK1 and SMAD7 in a subset of head and neck cancers
SO ONCOGENE
LA English
DT Article
DE TGF-beta TAK1; NF-kappa B; SMAD7; celastrol; head and neck cancer
ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR-BETA; INDUCED APOPTOSIS;
GENE-EXPRESSION; TUMOR-CELLS; KINASE TAK1; ACTIVATION; RECEPTOR;
PROTEIN; MICE
AB Transforming growth factor-beta (TGF-beta) has a dual role in epithelial malignancies, including head and neck squamous cell carcinoma (HNSCC). Attenuation of canonical TGF-beta signaling enhances de novo tumor development, whereas TGF-beta overexpression and signaling paradoxically promotes malignant progression. We recently observed that TGF-beta-induced growth arrest response is attenuated, in association with aberrant activation of nuclear factor-kappa B (NF-kappa B), a transcription factor, which promotes malignant progression in HNSCC. However, what role cross-talk between components of the TGF-beta and NF-kappa B pathways plays in altered activation of these pathways has not been established. Here, we show TGF-beta receptor II and TGF-beta-activated kinase 1 (TAK1) are predominantly expressed in a subset of HNSCC tumors with nuclear activation of NF-kappa B family member RELA (p65). Further, TGF-beta 1 treatment induced sequential phosphorylation of TAK1, IKK, I kappa B alpha and RELA in human HNSCC lines. TAK1 enhances TGF-beta-induced NF-kappa B activation, as TAK1 siRNA knockdown decreased TGF-beta 1-induced phosphorylation of IKK, I kappa B and RELA, degradation of I kappa B alpha, RELA nuclear translocation and DNA binding, and NF-kappa B-induced reporter and target gene transcription. Functionally, TAK1 siRNA inhibited cell proliferation, migration and invasion. Celastrol, a TAK1 inhibitor and anti-inflammatory compound used in traditional Chinese medicine, also decreased TGF-beta 1-induced phosphorylation of TAK1 and RELA, and suppressed basal, TGF-beta 1- and tumor necrosis factor-alpha (TNF-alpha)-induced NF-kappa B reporter gene activity. Celastrol also inhibited cell proliferation, while increasing sub-G0 DNA fragmentation and Annexin V markers of apoptosis. Furthermore, TGF-beta and RELA activation promoted SMAD7 expression. In turn, SMAD7 preferentially suppressed TGF-beta-induced SMAD and NF-kappa B reporters when compared with constitutive or TNF-alpha-induced NF-kappa B reporter gene activation. Thus, cross-talk by TGF-beta via TAK1 and NF-kappa B promotes the malignant phenotype of HNSCC. Moreover, NF-kappa B may contribute to the downstream attenuation of canonical TGF-beta signaling through increased SMAD7 expression. Celastrol highlights the therapeutic potential of agents targeting TAK1 as a key node in this pro-oncogenic TGF-beta-NF-kappa B signal pathway. Oncogene (2013) 32, 1549-1559; doi:10.1038/onc.2012.171; published online 28 May 2012
C1 [Freudlsperger, C.; Bian, Y.; Wise, S. Contag; Burnett, J.; Coupar, J.; Yang, X.; Chen, Z.; Van Waes, C.] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA.
[Freudlsperger, C.] Univ Hosp Tuebingen, Dept Oral & Maxillofacial Surg, Tubingen, Germany.
RP Chen, Z (reprint author), Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, 10 Ctr Dr,MSC 1462,Bldg 10,Rm 4-2732, Bethesda, MD 20892 USA.
EM chenz@nidcd.nih.gov; vanwaesc@nidcd.nih.gov
FU National Institute on Deafness and Other Communication Disorders, NIH
[ZIA-DC-000016, ZIA-DC-000073]; Clinical Research Training Program; NIH;
Pfizer Inc.
FX Supported by intramural projects ZIA-DC-000016 and ZIA-DC-000073 from
the National Institute on Deafness and Other Communication Disorders,
NIH. Dr Contag Wise was supported by the Clinical Research Training
Program, a public-private partnership supported jointly by the NIH and
Pfizer Inc. The authors wish to thank Dr Ning T Yeh (NIDCD/NIH) and
Chris Silvin (NHGRI/NIH) for their technical assistance. We would like
to thank Drs Adam Glick and Ashok Kulkarni for review of the manuscript
and helpful comments.
NR 61
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U1 1
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAR 21
PY 2013
VL 32
IS 12
BP 1549
EP 1559
DI 10.1038/onc.2012.171
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 110PC
UT WOS:000316456000008
PM 22641218
ER
PT J
AU Braun, R
Finney, R
Yan, CH
Chen, QR
Hu, Y
Edmonson, M
Meerzaman, D
Buetow, K
AF Braun, Rosemary
Finney, Richard
Yan, Chunhua
Chen, Qing-Rong
Hu, Ying
Edmonson, Michael
Meerzaman, Daoud
Buetow, Kenneth
TI Discovery Analysis of TCGA Data Reveals Association between Germline
Genotype and Survival in Ovarian Cancer Patients
SO PLOS ONE
LA English
DT Article
ID GENE-EXPRESSION; PLATINUM COMPLEXES; TUMOR RESPONSE; BREAST-CANCER;
CHEMOTHERAPY; CARCINOMA; SUSCEPTIBILITY; VARIANTS; POLYMORPHISMS;
PREDICTION
AB Background: Ovarian cancer remains a significant public health burden, with the highest mortality rate of all the gynecological cancers. This is attributable to the late stage at which the majority of ovarian cancers are diagnosed, coupled with the low and variable response of advanced tumors to standard chemotherapies. To date, clinically useful predictors of treatment response remain lacking. Identifying the genetic determinants of ovarian cancer survival and treatment response is crucial to the development of prognostic biomarkers and personalized therapies that may improve outcomes for the late-stage patients who comprise the majority of cases.
Methods: To identify constitutional genetic variations contributing to ovarian cancer mortality, we systematically investigated associations between germline polymorphisms and ovarian cancer survival using data from The Cancer Genome Atlas Project (TCGA). Using stage-stratified Cox proportional hazards regression, we examined >650,000 SNP loci for association with survival. We additionally examined whether the association of significant SNPs with survival was modified by somatic alterations.
Results: Germline polymorphisms at rs4934282 (AGAP11/C10orf116) and rs1857623 (DNAH14) were associated with stage-adjusted survival (p = 1.12e-07 and 1.80e-07, FDR q = 1.2e-04 and 2.4e-04, respectively). A third SNP, rs4869 (C10orf116), was additionally identified as significant in the exome sequencing data; it is in near-perfect LD with rs4934282. The associations with survival remained significant when somatic alterations.
Conclusions: Discovery analysis of TCGA data reveals germline genetic variations that may play a role in ovarian cancer survival even among late-stage cases. The significant loci are located near genes previously reported as having a possible relationship to platinum and taxol response. Because the variant alleles at the significant loci are common (frequencies for rs4934282 A/C alleles = 0.54/0.46, respectively; rs1857623 A/G alleles = 0.55/0.45, respectively) and germline variants can be assayed noninvasively, our findings provide potential targets for further exploration as prognostic biomarkers and individualized therapies.
C1 [Braun, Rosemary] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
[Braun, Rosemary; Finney, Richard; Yan, Chunhua; Chen, Qing-Rong; Hu, Ying; Edmonson, Michael; Meerzaman, Daoud; Buetow, Kenneth] NCI, Ctr Biomed Informat & Informat Technol, NIH, Bethesda, MD 20892 USA.
[Buetow, Kenneth] Arizona State Univ, Computat Sci & Informat Program, Complex Adapt Syst Initiat, Phoenix, AZ USA.
RP Braun, R (reprint author), Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
EM rbraun@northwestern.edu
OI Braun, Rosemary/0000-0001-9668-9866
FU National Cancer Institute, United States National Institutes of Health,
Bethesda, MD
FX The authors are supported by the Intramural Research Program of the
National Cancer Institute, United States National Institutes of Health,
Bethesda, MD. There were no external funding sources for this study. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 46
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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 MAR 21
PY 2013
VL 8
IS 3
AR e55037
DI 10.1371/journal.pone.0055037
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 111UM
UT WOS:000316546400001
PM 23555554
ER
PT J
AU Herman, JP
Cloud, CP
Wallman, J
AF Herman, James P.
Cloud, C. Phillip
Wallman, Josh
TI End-Point Variability Is Not Noise in Saccade Adaptation
SO PLOS ONE
LA English
DT Article
ID EYE-MOVEMENT; MOTOR ADAPTATION; ADAPTIVE-CONTROL; GAIN ADAPTATION;
PLASTICITY; SIGNALS; ERROR; SEQUENCES; MEMORY; SYSTEM
AB When each of many saccades is made to overshoot its target, amplitude gradually decreases in a form of motor learning called saccade adaptation. Overshoot is induced experimentally by a secondary, backwards intrasaccadic target step (ISS) triggered by the primary saccade. Surprisingly, however, no study has compared the effectiveness of different sizes of ISS in driving adaptation by systematically varying ISS amplitude across different sessions. Additionally, very few studies have examined the feasibility of adaptation with relatively small ISSs. In order to best understand saccade adaptation at a fundamental level, we addressed these two points in an experiment using a range of small, fixed ISS values (from 0 degrees to 1 degrees after a 10 degrees primary target step). We found that significant adaptation occurred across subjects with an ISS as small as 0.25 degrees. Interestingly, though only adaptation in response to 0.25 degrees ISSs appeared to be complete (the magnitude of change in saccade amplitude was comparable to size of the ISS), further analysis revealed that a comparable proportion of the ISS was compensated for across conditions. Finally, we found that ISS size alone was sufficient to explain the magnitude of adaptation we observed; additional factors did not significantly improve explanatory power. Overall, our findings suggest that current assumptions regarding the computation of saccadic error may need to be revisited.
C1 [Herman, James P.; Cloud, C. Phillip; Wallman, Josh] CUNY City Coll, Dept Biol, New York, NY 10031 USA.
[Herman, James P.; Wallman, Josh] CUNY, Grad Ctr, PhD Program Biol, New York, NY USA.
[Cloud, C. Phillip] CUNY, Grad Ctr, PhD Program Psychol, New York, NY USA.
RP Herman, JP (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM james.herman@nih.gov
OI Herman, James/0000-0001-6916-2807
FU National Science Foundation [BCS-0842464]; National Institute of Health
[1R01EY019508, RR-03060]
FX This research was funded by grant BCS-0842464 from the National Science
Foundation (www.nsf.gov), and grants 1R01EY019508 and RR-03060 from the
National Institute of Health (www.nih.gov). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript. No additional external funding was
received for this study.
NR 34
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Z9 7
U1 1
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 MAR 21
PY 2013
VL 8
IS 3
AR e59731
DI 10.1371/journal.pone.0059731
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 111UM
UT WOS:000316546400058
PM 23555763
ER
PT J
AU Koreishi, M
Gniadek, TJ
Yu, S
Masuda, J
Honjo, Y
Satoh, A
AF Koreishi, Mayuko
Gniadek, Thomas J.
Yu, Sidney
Masuda, Junko
Honjo, Yasuko
Satoh, Ayano
TI The Golgin Tether Giantin Regulates the Secretory Pathway by Controlling
Stack Organization within Golgi Apparatus
SO PLOS ONE
LA English
DT Article
ID ENDOPLASMIC-RETICULUM; TRYPANOSOMA-BRUCEI; TRANSPORT-VESICLE; PROTEIN
GIANTIN; COPI VESICLES; MEMBRANE; ARCHITECTURE; INTERACTS; P115;
DYNAMICS
AB Golgins are coiled-coil proteins that play a key role in the regulation of Golgi architecture and function. Giantin, the largest golgin in mammals, forms a complex with p115, rab1, GM130, and soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), thereby facilitating vesicle tethering and fusion processes around the Golgi apparatus. Treatment with the microtubule destabilizing drug nocodazole transforms the Golgi ribbon into individual Golgi stacks. Here we show that siRNA-mediated depletion of giantin resulted in more dispersed Golgi stacks after nocodazole treatment than by control treatment, without changing the average cisternal length. Furthermore, depletion of giantin caused an increase in cargo transport that was associated with altered cell surface protein glycosylation. Drosophila S2 cells are known to have dispersed Golgi stacks and no giantin homolog. The exogenous expression of mammalian giantin cDNA in S2 cells resulted in clustered Golgi stacks, similar to the Golgi ribbon in mammalian cells. These results suggest that the spatial organization of the Golgi ribbon is mediated by giantin, which also plays a role in cargo transport and sugar modifications.
C1 [Koreishi, Mayuko; Satoh, Ayano] Okayama Univ, Grad Sch Nat Sci & Technol, Okayama, Japan.
[Gniadek, Thomas J.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Yu, Sidney] Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China.
[Yu, Sidney] Chinese Univ Hong Kong, Epithelial Cell Biol Res Ctr, Shatin, Hong Kong, Peoples R China.
[Masuda, Junko] NIAID, Mucosal Immun Sect, Lab Host Def, NIH, Bethesda, MD 20892 USA.
[Honjo, Yasuko] Okayama Univ, RCIS, Okayama, Japan.
RP Satoh, A (reprint author), Okayama Univ, Grad Sch Nat Sci & Technol, Okayama, Japan.
EM ayano113@cc.okayama-u.ac.jp
OI SATOH, Ayano/0000-0003-3736-1283
FU Kurata Memorial Hitachi Science and Technology Foundation; special
Coordination Fund for Promoting Science and Technology; JSPS KAKENHI of
MEXT (Ministry of Education, Sport, Culture, Science and Technology in
Japan) [23570167]; Hayashi Memorial Foundation for Female Natural
Scientists; Ryobi Teien Memorial Foundation; Naito Foundation; Uehara
Memorial Foundation; National Institutes of Health, USA [AG030101,
GM060919]
FX Funding sources The Kurata Memorial Hitachi Science and Technology
Foundation, the special Coordination Fund for Promoting Science and
Technology, and JSPS KAKENHI Grant Number23570167 of MEXT (Ministry of
Education, Sport, Culture, Science and Technology in Japan), Hayashi
Memorial Foundation for Female Natural Scientists, Ryobi Teien Memorial
Foundation, the Naito Foundation, the Uehara Memorial Foundation, and
the National Institutes of Health (AG030101 and GM060919, USA). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 32
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U1 1
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 21
PY 2013
VL 8
IS 3
AR e59821
DI 10.1371/journal.pone.0059821
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 111UM
UT WOS:000316546400065
PM 23555793
ER
PT J
AU Rokic, MB
Stojilkovic, SS
Vavra, V
Kuzyk, P
Tvrdonova, V
Zemkova, H
AF Rokic, Milos B.
Stojilkovic, Stanko S.
Vavra, Vojtech
Kuzyk, Pavlo
Tvrdonova, Vendula
Zemkova, Hana
TI Multiple Roles of the Extracellular Vestibule Amino Acid Residues in the
Function of the Rat P2X4 Receptor
SO PLOS ONE
LA English
DT Article
ID HUMAN P2X(1) RECEPTORS; GATED ION CHANNELS; ATP-BINDING-SITE;
TRANSMEMBRANE SEGMENTS; AGONIST BINDING; LATERAL PORTALS;
IDENTIFICATION; PORE; MODULATION; ACTIVATION
AB The binding of ATP to trimeric P2X receptors (P2XR) causes an enlargement of the receptor extracellular vestibule, leading to opening of the cation-selective transmembrane pore, but specific roles of vestibule amino acid residues in receptor activation have not been evaluated systematically. In this study, alanine or cysteine scanning mutagenesis of V47-V61 and F324-N338 sequences of rat P2X4R revealed that V49, Y54, Q55, F324, and G325 mutants were poorly responsive to ATP and trafficking was only affected by the V49 mutation. The Y54F and Y54W mutations, but not the Y54L mutation, rescued receptor function, suggesting that an aromatic residue is important at this position. Furthermore, the Y54A and Y54C receptor function was partially rescued by ivermectin, a positive allosteric modulator of P2X4R, suggesting a rightward shift in the potency of ATP to activate P2X4R. The Q55T, Q55N, Q55E, and Q55K mutations resulted in non-responsive receptors and only the Q55E mutant was ivermectin-sensitive. The F324L, F324Y, and F324W mutations also rescued receptor function partially or completely, ivermectin action on channel gating was preserved in all mutants, and changes in ATP responsiveness correlated with the hydrophobicity and side chain volume of the substituent. The G325P mutant had a normal response to ATP, suggesting that G325 is a flexible hinge. A topological analysis revealed that the G325 and F324 residues disrupt a beta-sheet upon ATP binding. These results indicate multiple roles of the extracellular vestibule amino acid residues in the P2X4R function: the V49 residue is important for receptor trafficking to plasma membrane, the Y54 and Q55 residues play a critical role in channel gating and the F324 and G325 residues are critical for vestibule widening.
C1 [Rokic, Milos B.; Vavra, Vojtech; Kuzyk, Pavlo; Tvrdonova, Vendula; Zemkova, Hana] Acad Sci Czech Republic, Inst Physiol, Dept Cellular & Mol Neuroendocrinol, Prague, Czech Republic.
[Rokic, Milos B.; Tvrdonova, Vendula] Charles Univ Prague, Fac Sci, Dept Anim Physiol, Prague, Czech Republic.
[Stojilkovic, Stanko S.] NICHHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Rokic, MB (reprint author), Acad Sci Czech Republic, Inst Physiol, Dept Cellular & Mol Neuroendocrinol, Prague, Czech Republic.
EM rokic@biomed.cas.cz
RI Zemkova, Hana/C-1844-2012; Vavra, Vojtech/C-1857-2012; Tvrdonova
Stillerova, Vendula/G-3060-2014; ROKIC, MILOS/O-7204-2014
OI Tvrdonova Stillerova, Vendula/0000-0001-5295-2837; ROKIC,
MILOS/0000-0002-9148-2716
FU Internal Grant Agency of Academy of Sciences [IAA500110910]; Grant
Agency of the Czech Republic [P304/12/G069]; Grant Agency of Charles
University [3446/2011]; Academy of Sciences of the Czech Republic [AVOZ
50110509, RVO 67985823]; Intramural Research Program of the National
Institute of Child Health and Human Development (NICHD), National
Institutes of Health (NIH)
FX This work was supported by the Internal Grant Agency of Academy of
Sciences (Grant No. IAA500110910), the Grant Agency of the Czech
Republic (P304/12/G069), Grant Agency of Charles University (3446/2011),
the Academy of Sciences of the Czech Republic (Research Project No. AVOZ
50110509 and RVO 67985823), and the Intramural Research Program of the
National Institute of Child Health and Human Development (NICHD),
National Institutes of Health (NIH). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 52
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Z9 10
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 MAR 21
PY 2013
VL 8
IS 3
AR e59411
DI 10.1371/journal.pone.0059411
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 111UM
UT WOS:000316546400037
PM 23555667
ER
PT J
AU Chen, Q
Swaminathan, S
Yang, D
Dai, L
Sui, HY
Yang, J
Hornung, RL
Wang, YM
Huang, DW
Hu, XJ
Lempicki, RA
Imamichi, T
AF Chen, Qian
Swaminathan, Sanjay
Yang, De
Dai, Lue
Sui, Hongyan
Yang, Jun
Hornung, Ronald L.
Wang, Yanmei
Huang, Da Wei
Hu, Xiaojun
Lempicki, Richard A.
Imamichi, Tomozumi
TI Interleukin-27 Is a Potent Inhibitor of cis HIV-1 Replication in
Monocyte-Derived Dendritic Cells via a Type I Interferon-Independent
Pathway
SO PLOS ONE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4(+) T-CELLS; GASTROINTESTINAL-TRACT;
TRANS-INFECTION; CUTTING EDGE; IL-27; INDUCTION; DEPLETION; CYTOKINE;
IMMATURE
AB IL-27, a member of the IL-12 family of cytokines, plays an important and diverse role in the function of the immune system. Whilst generally recognized as an anti-inflammatory cytokine, in addition IL-27 has been found to have broad anti-viral effects. Recently, IL-27 has been shown to be a potent inhibitor of HIV-1 infection in CD4+ T cells and macrophages. The main objective of this study was to see whether IL-27 has a similar inhibitory effect on HIV-1 replication in dendritic cells (DCs). Monocytes were differentiated into immature DCs (iDCs) and mature DCs (mDCs) with standard techniques using a combination of GM-CSF, IL-4 and LPS. Following differentiation, iDCs were infected with HIV-1 and co-cultured in the presence or absence of IL-27. IL-27 treated DCs were shown to be highly potent inhibitors of cis HIV-1, particularly of CCR5 tropic strains. Of note, other IL-12 family members (IL-12, IL-23 and IL-35) had no effect on HIV-1 replication. Microarray studies of IL-27 treated DCs showed no up-regulation of Type I (IFN) gene expression. Neutralization of the Type-I IFN receptor had no impact on the HIV inhibition. Lastly, IL-27 mediated inhibition was shown to act post-viral entry and prior to completion of reverse transcription. These results show for the first time that IL-27 is a potent inhibitor of cis HIV-1 infection in DCs by a Type I IFN independent mechanism. IL-27 has previously been reported to inhibit HIV-1 replication in CD4+ T cells and macrophages, thus taken together, this cytokine is a potent anti-HIV agent against all major cell types targeted by the HIV-1 virus and may have a therapeutic role in the future.
C1 [Chen, Qian; Swaminathan, Sanjay; Dai, Lue; Sui, Hongyan; Imamichi, Tomozumi] Sci Applicat Int Corp SAIC Frederick Inc, Appl & Dev Res Directorate ADD, Lab Human Retrovirol, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Yang, De] SAIC Frederick Inc, Basic Res Program Directorate, Mol Immunoregulat Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Yang, Jun; Huang, Da Wei; Hu, Xiaojun; Lempicki, Richard A.] SAIC Frederick Inc, Lab Immunopathogenesis & Bioinformat, ADD, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Hornung, Ronald L.; Wang, Yanmei] SAIC Frederick Inc, Immunol Monitoring Lab, ADD, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Imamichi, T (reprint author), Sci Applicat Int Corp SAIC Frederick Inc, Appl & Dev Res Directorate ADD, Lab Human Retrovirol, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM timamichi@mail.nih.gov
RI Sui, Hongyan/M-1305-2013; Lempicki, Richard/E-1844-2012;
OI Lempicki, Richard/0000-0002-7059-409X; Swaminathan,
Sanjay/0000-0001-5315-6445
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institute of Allergy and Infectious
Disease
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 National Institute of
Allergy and Infectious Disease. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 39
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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 MAR 20
PY 2013
VL 8
IS 3
AR e59194
DI 10.1371/journal.pone.0059194
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125SW
UT WOS:000317562600063
PM 23527130
ER
PT J
AU Fenichel, EP
Kuminoff, NV
Chowell, G
AF Fenichel, Eli P.
Kuminoff, Nicolai V.
Chowell, Gerardo
TI Skip the Trip: Air Travelers' Behavioral Responses to Pandemic Influenza
SO PLOS ONE
LA English
DT Article
ID INFECTIOUS-DISEASES; A H1N1; TRANSMISSION; IMPACT; SPREAD; MODELS;
STRAIN; UK
AB Theory suggests that human behavior has implications for disease spread. We examine the hypothesis that individuals engage in voluntary defensive behavior during an epidemic. We estimate the number of passengers missing previously purchased flights as a function of concern for swine flu or A/H1N1 influenza using 1.7 million detailed flight records, Google Trends, and the World Health Organization's FluNet data. We estimate that concern over "swine flu," as measured by Google Trends, accounted for 0.34% of missed flights during the epidemic. The Google Trends data correlates strongly with media attention, but poorly (at times negatively) with reported cases in FluNet. Passengers show no response to reported cases. Passengers skipping their purchased trips forwent at least $50 M in travel related benefits. Responding to actual cases would have cut this estimate in half. Thus, people appear to respond to an epidemic by voluntarily engaging in self-protection behavior, but this behavior may not be responsive to objective measures of risk. Clearer risk communication could substantially reduce epidemic costs. People undertaking costly risk reduction behavior, for example, forgoing nonrefundable flights, suggests they may also make less costly behavior adjustments to avoid infection. Accounting for defensive behaviors may be important for forecasting epidemics, but linking behavior with epidemics likely requires consideration of risk communication.
C1 [Fenichel, Eli P.] Yale Univ, Sch Forestry & Environm Studies, New Haven, CT 06511 USA.
[Kuminoff, Nicolai V.] Arizona State Univ, Dept Econ, Tempe, AZ 85287 USA.
[Chowell, Gerardo] Arizona State Univ, Sch Human Evolut, Tempe, AZ USA.
[Chowell, Gerardo] Arizona State Univ, Sch Change, Tempe, AZ USA.
[Chowell, Gerardo] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Fenichel, EP (reprint author), Yale Univ, Sch Forestry & Environm Studies, New Haven, CT 06511 USA.
EM eli.fenichel@yale.edu
RI Chowell, Gerardo/F-5038-2012;
OI Chowell, Gerardo/0000-0003-2194-2251; Fenichel, Eli/0000-0002-7649-8250
FU National Institute of General Medical Sciences (NIGMS) at the National
Institutes of Health [1R01GM100471-01]
FX U.S. Airways Corporation generously provided data and background
information on the airline industry. This publication was made possible
by grant number 1R01GM100471-01 from the National Institute of General
Medical Sciences (NIGMS) at the National Institutes of Health. Its
contents are solely the responsibility of the authors and do not
represent the official views of NIGMS or US Airways. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 47
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U1 1
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 MAR 20
PY 2013
VL 8
IS 3
AR e58249
DI 10.1371/journal.pone.0058249
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125SW
UT WOS:000317562600015
PM 23526970
ER
PT J
AU Toro, C
Olive, M
Dalakas, MC
Sivakumar, K
Bilbao, JM
Tyndel, F
Vidal, N
Farrero, E
Sambuughin, N
Goldfarb, LG
AF Toro, Camilo
Olive, Montse
Dalakas, Marinos C.
Sivakumar, Kumaraswami
Bilbao, Juan M.
Tyndel, Felix
Vidal, Noemi
Farrero, Eva
Sambuughin, Nyamkhishig
Goldfarb, Lev G.
TI Exome sequencing identifies titin mutations causing hereditary myopathy
with early respiratory failure (HMERF) in families of diverse ethnic
origins
SO BMC NEUROLOGY
LA English
DT Article
DE Myopathy; Respiratory failure; HMERF; Titin; Titin A-band mutation;
Fibronectin type III
ID PROTEIN AGGREGATE MYOPATHIES; AUTOSOMAL-DOMINANT MYOPATHY;
CYCLIN-DEPENDENT KINASES; MYOFIBRILLAR MYOPATHY; MUSCULAR-DYSTROPHY;
DILATED CARDIOMYOPATHY; TDP-43 ACCUMULATION; ONSET MYOPATHY; Z-LINE;
MUSCLE
AB Background: Hereditary myopathy with early respiratory failure (HMERF) was described in several North European families and recently linked to a titin gene (TTN) mutation. We independently studied HMERF-like diseases with the purpose to identify the cause, refine diagnostic criteria, and estimate the frequency of this disease among myopathy patients of various ethnic origins.
Methods: Whole exome sequencing analysis was carried out in a large U. S. family that included seven members suffering from skeletal muscle weakness and respiratory failure. Subsequent mutation screening was performed in further 45 unrelated probands with similar phenotypes. Studies included muscle strength evaluation, nerve conduction studies and concentric needle EMG, respiratory function test, cardiologic examination, and muscle biopsy.
Results: A novel TTN p.Gly30150Asp mutation was identified in the highly conserved A-band of titin that co-segregated with the disease in the U. S. family. Screening of 45 probands initially diagnosed as myofibrillar myopathy (MFM) but excluded based on molecular screening for the known MFM genes led to the identification of a previously reported TTN p.Cys30071Arg mutation in one patient. This same mutation was also identified in a patient with suspected HMERF. The p.Gly30150Asp and p.Cys30071Arg mutations are localized to a side chain of fibronectin type III element A150 of the 10th C-zone super-repeat of titin.
Conclusions: Missense mutations in TTN are the cause of HMERF in families of diverse origins. A comparison of phenotypic features of HMERF caused by the three known TTN mutations in various populations allowed to emphasize distinct clinical/pathological features that can serve as the basis for diagnosis. The newly identified p.Gly30150Asp and the p.Cys30071Arg mutation are localized to a side chain of fibronectin type III element A150 of the 10th C-zone super-repeat of titin.
C1 [Toro, Camilo] NHGRI, Undiagnosed Dis Program, NIH, Bethesda, MD 20892 USA.
[Olive, Montse; Vidal, Noemi] IDIBELL Hosp Univ Bellvitge, Dept Pathol, Inst Neuropathol, Barcelona, Spain.
[Olive, Montse] IDIBELL Hosp Univ Bellvitge, Dept Neurol, Neuromuscular Unit, Barcelona, Spain.
[Olive, Montse] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain.
[Dalakas, Marinos C.] Univ Athens, Sch Med, GR-11527 Athens, Greece.
[Sivakumar, Kumaraswami] Barrow Neurol Inst, Phoenix, AZ 85013 USA.
[Bilbao, Juan M.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada.
[Tyndel, Felix] Univ Toronto, Toronto Western Hosp, Toronto, ON M5T 2S8, Canada.
[Farrero, Eva] IDIBELL Hosp Univ Bellvitge, Pneumol Serv, Barcelona, Spain.
[Sambuughin, Nyamkhishig] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Goldfarb, Lev G.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Goldfarb, LG (reprint author), NINDS, NIH, Room 4S06,5625 Fishers Lane,MSC 9404, Bethesda, MD 20892 USA.
EM GoldfarbL@ninds.nih.gov
OI Olive, Montse/0000-0001-5727-0165
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke; Spanish Instituto de Salud Carlos III [PI08-574];
USU [R080CD]
FX We wish to thank D.O. Furst for providing the anti C-filamin antibody.
The research was supported in part by the Intramural Research Program of
the National Institute of Neurological Disorders and Stroke. Technical
support was provided by the Bioinformatics core at the Undiagnosed
Diseases Program, National Human Genome Research Institute, National
Institutes of Health and Biomedical Instrumentation Center of USU,
Uniformed Services University. MO was supported by a grant from the
Spanish Instituto de Salud Carlos III, PI08-574. NS was supported by USU
grant R080CD.
NR 51
TC 17
Z9 18
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2377
J9 BMC NEUROL
JI BMC Neurol.
PD MAR 20
PY 2013
VL 13
AR 29
DI 10.1186/1471-2377-13-29
PG 14
WC Clinical Neurology
SC Neurosciences & Neurology
GA 113WW
UT WOS:000316701100001
PM 23514108
ER
PT J
AU Brady, LS
AF Brady, Linda S.
TI Assessing biomarkers for brain diseases: progress and gaps
SO GENOME MEDICINE
LA English
DT Editorial Material
AB A report on the 2nd Wellcome Trust Scientific Conference on Biomarkers for Brain Disorders: Challenges and Opportunities, held at the Moller Centre, Cambridge, UK, February 3-5, 2013.
C1 NIMH, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA.
RP Brady, LS (reprint author), NIMH, Div Neurosci & Basic Behav Sci, 6001 Execut Blvd, Bethesda, MD 20892 USA.
EM lbrady@mail.nih.gov
NR 0
TC 0
Z9 1
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-994X
J9 GENOME MED
JI Genome Med.
PD MAR 20
PY 2013
VL 5
AR 23
DI 10.1186/gm427
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 115FP
UT WOS:000316798300001
PM 23673002
ER
PT J
AU Li, ZJ
Herold, T
He, CJ
Valk, PJM
Chen, P
Jurinovic, V
Mansmann, U
Radmacher, MD
Maharry, KS
Sun, M
Yang, XN
Huang, H
Jiang, X
Sauerland, MC
Buchner, T
Hiddemann, W
Elkahloun, A
Neilly, MB
Zhang, YM
Larson, RA
Le Beau, MM
Caligiuri, MA
Dohner, K
Bullinger, L
Liu, PP
Delwel, R
Marcucci, G
Lowenberg, B
Bloomfield, CD
Rowley, JD
Bohlander, SK
Chen, JJ
AF Li, Zejuan
Herold, Tobias
He, Chunjiang
Valk, Peter J. M.
Chen, Ping
Jurinovic, Vindi
Mansmann, Ulrich
Radmacher, Michael D.
Maharry, Kati S.
Sun, Miao
Yang, Xinan
Huang, Hao
Jiang, Xi
Sauerland, Maria-Cristina
Buechner, Thomas
Hiddemann, Wolfgang
Elkahloun, Abdel
Neilly, Mary Beth
Zhang, Yanming
Larson, Richard A.
Le Beau, Michelle M.
Caligiuri, Michael A.
Doehner, Konstanze
Bullinger, Lars
Liu, Paul P.
Delwel, Ruud
Marcucci, Guido
Lowenberg, Bob
Bloomfield, Clara D.
Rowley, Janet D.
Bohlander, Stefan K.
Chen, Jianjun
TI Identification of a 24-Gene Prognostic Signature That Improves the
European LeukemiaNet Risk Classification of Acute Myeloid Leukemia: An
International Collaborative Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ACUTE MYELOGENOUS LEUKEMIA; GENE-EXPRESSION SIGNATURE; NORMAL
CYTOGENETICS; GROUP-B; CEBPA MUTATIONS; POOR-PROGNOSIS; TANDEM
DUPLICATION; NORMAL KARYOTYPE; YOUNGER ADULTS; FAVORABLE PROGNOSIS
AB Purpose
To identify a robust prognostic gene expression signature as an independent predictor of survival of patients with acute myeloid leukemia (AML) and use it to improve established risk classification.
Patients and Methods
Four independent sets totaling 499 patients with AML carrying various cytogenetic and molecular abnormalities were used as training sets. Two independent patient sets composed of 825 patients were used as validation sets. Notably, patients from different sets were treated with different protocols, and their gene expression profiles were derived using different microarray platforms. Cox regression and Kaplan-Meier methods were used for survival analyses.
Results
A prognostic signature composed of 24 genes was derived from a meta-analysis of Cox regression values of each gene across the four training sets. In multivariable models, a higher sum value of the 24-gene signature was an independent predictor of shorter overall (OS) and event-free survival (EFS) in both training and validation sets (P < .01). Moreover, this signature could substantially improve the European LeukemiaNet (ELN) risk classification of AML, and patients in three new risk groups classified by the integrated risk classification showed significantly (P < .001) distinct OS and EFS.
Conclusion
Despite different treatment protocols applied to patients and use of different microarray platforms for expression profiling, a common prognostic gene signature was identified as an independent predictor of survival of patients with AML. The integrated risk classification incorporating this gene signature provides a better framework for risk stratification and outcome prediction than the ELN classification. J Clin Oncol 31:1172-1181. (C) 2013 by American Society of Clinical Oncology
C1 [Li, Zejuan; He, Chunjiang; Chen, Ping; Sun, Miao; Yang, Xinan; Huang, Hao; Jiang, Xi; Neilly, Mary Beth; Larson, Richard A.; Le Beau, Michelle M.; Rowley, Janet D.; Chen, Jianjun] Univ Chicago, Chicago, IL 60637 USA.
[Zhang, Yanming] Northwestern Univ, Chicago, IL 60611 USA.
[Herold, Tobias; Hiddemann, Wolfgang; Bohlander, Stefan K.] Univ Hosp Grosshadern, Munich, Germany.
[Herold, Tobias; Jurinovic, Vindi; Mansmann, Ulrich; Hiddemann, Wolfgang; Bohlander, Stefan K.] Univ Munich, Munich, Germany.
[Sauerland, Maria-Cristina; Buechner, Thomas] Univ Munster, D-48149 Munster, Germany.
[Doehner, Konstanze; Bullinger, Lars] Univ Ulm, D-89069 Ulm, Germany.
[Bohlander, Stefan K.] Univ Marburg, Marburg, Germany.
[Valk, Peter J. M.; Delwel, Ruud; Lowenberg, Bob] Erasmus Univ, Med Ctr, Rotterdam, Netherlands.
[Radmacher, Michael D.; Maharry, Kati S.; Caligiuri, Michael A.; Marcucci, Guido; Bloomfield, Clara D.] Ohio State Univ, Columbus, OH 43210 USA.
[Elkahloun, Abdel; Liu, Paul P.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Chen, JJ (reprint author), Univ Chicago, Dept Med, 900 E 57th St,Room 7134, Chicago, IL 60637 USA.
EM jchen@medicine.bsd.uchicago.edu
RI Liu, Paul/A-7976-2012; Sauerland , Maria Cristina /A-4154-2014;
OI Liu, Paul/0000-0002-6779-025X; Bohlander, Stefan/0000-0002-2202-9088;
He, Chunjiang/0000-0002-4868-331X; Herold, Tobias/0000-0002-9615-9432;
Larson, Richard/0000-0001-9168-3203
FU Leukemia and Lymphoma Society (LLS) [6199-09]; Cancer and Leukemia Group
B (CALGB) Pilot Grant [20801]; German Ministry of Education and Research
National Genome Research Network [01G0876]; Dutch Cancer Foundation;
National Institutes of Health (NIH) [R01 CA127277, P01 CA40046];
American Cancer Society [120993-RSG-11-156-01-LIB]; LLS Special
Fellowship; G. Harold and Leila Y. Mathers Charitable Foundation;
Gabrielle's Angel Foundation for Cancer Research; CALGB Leukemia
Correlative Science Committee [U10 CA101140]; Ohio State University
Leukemia Specialized Program of Research Excellence [P50CA140158];
Leukemia Clinical Research Foundation; NIH Intramural Research Program
of the National Human Genome Research Institute; Department of Defense
[W81XWH-10-1-0396]; National Natural Science Foundation of China
[60971099]; Deutsche Jose Carreras Leukamie Stiftung [R 06/41v];
Deutsche Forschungsgemeinschaft Heisenberg-Stipendium [BU1339/3-1];
National Cancer Institute Cancer Center [P30 CA014599]; University of
Chicago Committee on Cancer Biology Fellowship Program; Spastic
Paralysis Foundation of the Illinois/Eastern Iowa Branch of Kiwanis
International; Fidelity Foundation
FX Supported in part by the Leukemia and Lymphoma Society (LLS)
Translational Research Grant No. 6199-09 (J.D.R., J.C.), Cancer and
Leukemia Group B (CALGB) Pilot Grant No. 20801 (J.D.R., J.C.), German
Ministry of Education and Research National Genome Research Network
Grant No. 01G0876 (S.K.B.), the Dutch Cancer Foundation Queen Wilhelmina
Fund (P.J.M.V., R.D., B.L.), National Institutes of Health (NIH) Grant
No. R01 CA127277 (J.C.), American Cancer Society Research Scholar Grant
No. 120993-RSG-11-156-01-LIB (J.C.), an LLS Special Fellowship (Z.L.),
the G. Harold and Leila Y. Mathers Charitable Foundation (J.C.),
Gabrielle's Angel Foundation for Cancer Research (Z.L., X.J., H.H.,
J.C.), CALGB Leukemia Correlative Science Committee Grant No. U10
CA101140 (G.M.), Ohio State University Leukemia Specialized Program of
Research Excellence Grant No. P50CA140158 Project 2 (G.M., C.D.B.),
Leukemia Clinical Research Foundation grant (G.M., C.D.B.), the NIH
Intramural Research Program of the National Human Genome Research
Institute (A.E., P.P.L.), Department of Defense Predoctoral Traineeship
Award No. W81XWH-10-1-0396 (M.S.), National Natural Science Foundation
of China Grant No. 60971099 (X.Y.), Deutsche Jose Carreras Leukamie
Stiftung Grant No. R 06/41v (L.B.), Deutsche Forschungsgemeinschaft
Heisenberg-Stipendium Grant No. BU1339/3-1 (L.B.), NIH Grant No. P01
CA40046 (M.M.L.B.), National Cancer Institute Cancer Center Support
Grant No. P30 CA014599 (M.M.L.B.), the University of Chicago Committee
on Cancer Biology Fellowship Program (X.J.), the Spastic Paralysis
Foundation of the Illinois/Eastern Iowa Branch of Kiwanis International
(J.D.R.), and the Fidelity Foundation (J.D.R., J.C.).
NR 59
TC 42
Z9 42
U1 0
U2 11
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 MAR 20
PY 2013
VL 31
IS 9
BP 1172
EP 1181
DI 10.1200/JCO.2012.44.3184
PG 10
WC Oncology
SC Oncology
GA 107AS
UT WOS:000316187600017
PM 23382473
ER
PT J
AU Scimemi, A
Meabon, JS
Woltjer, RL
Sullivan, JM
Diamond, JS
Cook, DG
AF Scimemi, Annalisa
Meabon, James S.
Woltjer, Randall L.
Sullivan, Jane M.
Diamond, Jeffrey S.
Cook, David G.
TI Amyloid-beta(1-42) Slows Clearance of Synaptically Released Glutamate by
Mislocalizing Astrocytic GLT-1
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ALZHEIMERS-DISEASE; TRANSPORTER GLT-1; BRAIN; BETA; NEURODEGENERATION;
EXPRESSION; MECHANISM; NEURONS; PATHWAY; PROTECT
AB GLT-1, the major glutamate transporter in the adult brain, is abundantly expressed in astrocytic processes enveloping synapses. By limiting glutamate escape into the surrounding neuropil, GLT-1 preserves the spatial specificity of synaptic signaling. Here we show that the amyloid-beta peptide A beta(1-42) markedly prolongs the extracellular lifetime of synaptically released glutamate by reducing GLT-1 surface expression in mouse astrocytes and that this effect is prevented by the vitamin E derivative Trolox. These findings indicate that astrocytic glutamate transporter dysfunction may play an important role in the pathogenesis of Alzheimer's disease and suggest possible mechanisms by which several current treatment strategies could protect against the disease.
C1 [Scimemi, Annalisa; Diamond, Jeffrey S.] NINDS, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA.
[Meabon, James S.] Univ Washington, Dept Psychiat, Seattle, WA 98108 USA.
[Cook, David G.] Univ Washington, Dept Med, Seattle, WA 98108 USA.
[Cook, David G.] Univ Washington, Dept Pharmacol, Seattle, WA 98108 USA.
[Sullivan, Jane M.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA.
[Meabon, James S.; Cook, David G.] VA Puget Sound Hlth Care Syst, Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA.
[Woltjer, Randall L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA.
RP Cook, DG (reprint author), VA Med Ctr, GRECC, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM dgcook@u.washington.edu
RI Scimemi, Annalisa/O-5396-2014; Diamond, Jeffrey/C-1835-2015
OI Scimemi, Annalisa/0000-0003-4975-093X; Diamond,
Jeffrey/0000-0002-1770-2629
FU Veteran's Affairs Office of Research and Development Medical Research
Service; NIH [T32 AG000258, RO1 NS055804]; NINDS [NS002986]
FX This work was supported by the Veteran's Affairs Office of Research and
Development Medical Research Service (D. G. C.), NIH (Grants T32
AG000258, J.S.M.; and RO1 NS055804, J.M.S.), and NINDS Intramural
Research Program (Grant NS002986, J.S.D.). We thank Mike Ahlquist, Ping
Zhu, and Ning Li for excellent technical assistance.
NR 28
TC 29
Z9 30
U1 1
U2 10
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 20
PY 2013
VL 33
IS 12
BP 5312
EP 5318
DI 10.1523/JNEUROSCI.5274-12.2013
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 111XB
UT WOS:000316553800023
PM 23516295
ER
PT J
AU Herring, BE
Shi, Y
Suh, YH
Zheng, CY
Blankenship, SM
Roche, KW
Nicoll, RA
AF Herring, Bruce E.
Shi, Yun
Suh, Young Ho
Zheng, Chan-Ying
Blankenship, Sabine M.
Roche, Katherine W.
Nicoll, Roger A.
TI Cornichon Proteins Determine the Subunit Composition of Synaptic AMPA
Receptors
SO NEURON
LA English
DT Article
ID TRANSMEMBRANE AUXILIARY SUBUNITS; GLUTAMATE RECEPTORS; TARPS;
PLASTICITY; TRAFFICKING; EXPRESSION; DROSOPHILA; NEURONS; NUMBER; MICE
AB Cornichon-2 and cornichon-3 (CNIH-2/-3) are AMPA receptor (AMPAR) binding proteins that promote receptor trafficking and markedly slow AMPAR deactivation in heterologous cells, but their role in neurons is unclear. Using CNIH-2 and CNIH-3 conditional knockout mice, we find a profound reduction of AMPAR synaptic transmission in the hippocampus. This deficit is due to the selective loss of surface GluA1-containing AMPARs (GluA1A2 heteromers), leaving a small residual pool of synaptic GluA2A3 heteromers. The kinetics of AMPARs in neurons lacking CNIH-2/-3 are faster than those in WT neurons due to the fast kinetics of GluA2A3 heteromers. The remarkably selective effect of CNIHs on the GluA1 subunit is probably mediated by TARP gamma-8, Which prevents a functional association of CNIHs with non-GluA1 subunits. These results point to a sophisticated interplay between CNIHs and gamma-8 that dictates subunit-specific AMPAR trafficking and the strength and kinetics of synaptic AMPAR-mediated transmission.
C1 [Herring, Bruce E.; Shi, Yun; Blankenship, Sabine M.; Nicoll, Roger A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
[Herring, Bruce E.; Shi, Yun; Blankenship, Sabine M.; Nicoll, Roger A.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
[Suh, Young Ho] Ajou Univ, Sch Med, Chron Inflammatory Dis Res Ctr, Dept Pharmacol, Suwon 443721, South Korea.
[Zheng, Chan-Ying; Roche, Katherine W.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Suh, YH (reprint author), Ajou Univ, Sch Med, Chron Inflammatory Dis Res Ctr, Dept Pharmacol, Suwon 443721, South Korea.
EM suhy@ajou.ac.kr; roger.nicoll@ucsf.edu
RI Shi, Yun/B-5623-2009;
OI Roche, Katherine/0000-0001-7282-6539
FU US NIMH; NARSAD grant from the Brain and Behavior Research Fund;
Intramural Research Program of NINDS; Basic Science Research Program
[2011-0011694]; MRC through the National Research Foundation of Korea
[2012048183]
FX This work was funded by grants from the US NIMH to R.A.N. and a NARSAD
grant from the Brain and Behavior Research Fund to B.E.H. C.-Y.Z. and
K.W.R. were supported by the Intramural Research Program of NINDS.
Y.H.S. was supported by the Basic Science Research Program
(2011-0011694) and MRC (2012048183) through the National Research
Foundation of Korea.
NR 27
TC 41
Z9 41
U1 0
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD MAR 20
PY 2013
VL 77
IS 6
BP 1083
EP 1096
DI 10.1016/j.neuron.2013.01.017
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 113CX
UT WOS:000316645000010
PM 23522044
ER
PT J
AU Abraham, BJ
Cui, KR
Tang, QS
Zhao, KJ
AF Abraham, Brian J.
Cui, Kairong
Tang, Qingsong
Zhao, Keji
TI Dynamic regulation of epigenomic landscapes during hematopoiesis
SO BMC GENOMICS
LA English
DT Article
DE Epigenetics; Hematopoiesis; Gene expression; Histone modifications
ID EMBRYONIC STEM-CELLS; HUMAN GENOME; HISTONE H3; GENE-EXPRESSION;
CHROMATIN SIGNATURES; LYSINE-27 METHYLATION; ACTIVE PROMOTERS;
EPIGENETIC MARK; T-CELLS; B-CELLS
AB Background: Human blood develops from self-renewing hematopoietic stem cells to terminal lineages and necessitates regulator and effector gene expression changes; each cell type specifically expresses a subset of genes to carry out a specific function. Gene expression changes coincide with histone modification, histone variant deposition, and recruitment of transcription-related enzymes to specific genetic loci. Transcriptional regulation has been mostly studied using in vitro systems while epigenetic changes occurring during in vivo development remain poorly understood.
Results: By integrating previously published and novel global expression profiles from human CD34+/CD133+ hematopoietic stem and progenitor cells (HSPCs), in vivo differentiated human CD4+ T-cells and CD19+ B-cells, and in vitro differentiated CD36+ erythrocyte precursors, we identified hundreds of transcripts specifically expressed in each cell type. To relate concurrent epigenomic changes to expression, we examined genome-wide distributions of H3K4me1, H3K4me3, H3K27me1, H3K27me3, histone variant H2A.Z, ATP-dependent chromatin remodeler BRG1, and RNA Polymerase II in these cell types, as well as embryonic stem cells. These datasets revealed that numerous differentiation genes are primed for subsequent downstream expression by BRG1 and PolII binding in HSPCs, as well as the bivalent H3K4me3 and H3K27me3 modifications in the HSPCs prior to their expression in downstream, differentiated cell types; much HSPC bivalency is retained from embryonic stem cells. After differentiation, bivalency resolves to active chromatin configuration in the specific lineage, while it remains in parallel differentiated lineages. PolII and BRG1 are lost in closer lineages; bivalency resolves to silent monovalency in more distant lineages.
Correlation of expression with epigenomic changes predicts tens of thousands of potential common and tissue-specific enhancers, which may contribute to expression patterns and differentiation pathways.
Conclusions: Several crucial lineage factors are bivalently prepared for their eventual expression or repression. Bivalency is not only resolved during differentiation but is also established in a step-wise manner in differentiated cell types. We note a progressive, specific silencing of alternate lineage genes in certain cell types coinciding with H3K27me3 enrichment, though expression silencing is maintained in its absence. Globally, the expression of type-specific genes across many cell types correlates strongly with their epigenetic profiles. These epigenomic data appear useful for further understanding mechanisms of differentiation and function of human blood lineages.
C1 [Abraham, Brian J.; Cui, Kairong; Tang, Qingsong; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Abraham, Brian J.] Boston Univ, Bioinformat Program, Boston, MA 02215 USA.
RP Zhao, KJ (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM zhaok@nhlbi.nih.gov
OI Abraham, Brian/0000-0001-8085-3027
FU Division of Intramural Research Program of the National Institute of
Heart, Lung and Blood Institute, NIH
FX We would like to thank Dr. Thomas Tullius at Boston University for
critical reading of the manuscript and Dr. Weiqun Peng for helpful
discussion. The DNA Sequencing Core and the Flow Cytometry Core of NHLBI
assisted with this work. This work was supported by the Division of
Intramural Research Program of the National Institute of Heart, Lung and
Blood Institute, NIH.
NR 77
TC 16
Z9 17
U1 2
U2 14
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 MAR 19
PY 2013
VL 14
AR 193
DI 10.1186/1471-2164-14-193
PG 15
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 131YS
UT WOS:000318035400001
PM 23510235
ER
PT J
AU Boonyaratanakornkit, J
Schomacker, H
Collins, P
Schmidt, A
AF Boonyaratanakornkit, Jim
Schomacker, Henrick
Collins, Peter
Schmidt, Alexander
TI Alix Serves as an Adaptor That Allows Human Parainfluenza Virus Type 1
to Interact with the Host Cell ESCRT System
SO PLOS ONE
LA English
DT Article
ID ALG-2-INTERACTING PROTEIN ALIX; SENDAI-VIRUS; C-PROTEIN; VACCINE
CANDIDATES; BINDING PARTNER; P/C GENE; ATTENUATING MUTATIONS; REVERSE
GENETICS; BRO1 DOMAIN; WILD-TYPE
AB The cellular ESCRT (endosomal sorting complex required for transport) system functions in cargo-sorting, in the formation of intraluminal vesicles that comprise multivesicular bodies (MVB), and in cytokinesis, and this system can be hijacked by a number of enveloped viruses to promote budding. The respiratory pathogen human parainfluenza virus type I (HPIV1) encodes a nested set of accessory C proteins that play important roles in down-regulating viral transcription and replication, in suppressing the type I interferon (IFN) response, and in suppressing apoptosis. Deletion or mutation of the C proteins attenuates HPIV1 in vivo, and such mutants are being evaluated preclinically and clinically as vaccines. We show here that the C proteins interact and co-localize with the cellular protein Alix, which is a member of the class E vacuolar protein sorting (Vps) proteins that assemble at endosomal membranes into ESCRT complexes. The HPIV1 C proteins interact with the Bro1 domain of Alix at a site that is also required for the interaction between Alix and Chmp4b, a subunit of ESCRT-III. The C proteins are ubiquitinated and subjected to proteasome-mediated degradation, but the interaction with Alix(Bro1) protects the C proteins from degradation. Neither over-expression nor knock-down of Alix expression had an effect on HPIV1 replication, although this might be due to the large redundancy of Alix-like proteins. In contrast, knocking down the expression of Chmp4 led to an approximately 100-fold reduction in viral titer during infection with wild-type (WT) HPIV1. This level of reduction was similar to that observed for the viral mutant, P(C-) HPIV1, in which expression of the C proteins were knocked out. Chmp4 is capable of out-competing the HPIV1 C proteins for binding Alix. Together, this suggests a possible model in which Chmp4, through Alix, recruits the C proteins to a common site on intracellular membranes and facilitates budding.
C1 [Boonyaratanakornkit, Jim; Schomacker, Henrick; Collins, Peter; Schmidt, Alexander] NIAID, Infect Dis Lab, RNA Viruses Sect, NIH, Bethesda, MD 20892 USA.
RP Schmidt, A (reprint author), NIAID, Infect Dis Lab, RNA Viruses Sect, NIH, Bethesda, MD 20892 USA.
EM as337y@gmail.com
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 51
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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 MAR 19
PY 2013
VL 8
IS 3
AR e59462
DI 10.1371/journal.pone.0059462
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125SR
UT WOS:000317562100137
PM 23527201
ER
PT J
AU Roth, BL
Gibbons, S
Arunotayanun, W
Huang, XP
Setola, V
Treble, R
Iversen, L
AF Roth, Bryan L.
Gibbons, Simon
Arunotayanun, Warunya
Huang, Xi-Ping
Setola, Vincent
Treble, Ric
Iversen, Les
TI The Ketamine Analogue Methoxetamine and 3-and 4-Methoxy Analogues of
Phencyclidine Are High Affinity and Selective Ligands for the Glutamate
NMDA Receptor
SO PLOS ONE
LA English
DT Article
ID AGONIST
AB In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as 'designer drugs' and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS)-2-(ethylamino)-2-(3-methoxyphenyl)cyclohexanone) and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenyl)cyclohexanamine) and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenyl)cyclohexyl]piperidine and 1-[1-(4-methoxyphenyl) cyclohexyl] piperidine), were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.
C1 [Roth, Bryan L.; Huang, Xi-Ping; Setola, Vincent] Univ N Carolina, Chapel Hill Med Sch, Dept Pharmacol, NIMH Psychoact Drug Screening Program, Chapel Hill, NC USA.
[Roth, Bryan L.; Huang, Xi-Ping; Setola, Vincent] Univ N Carolina, Chapel Hill Med Sch, Div Chem Biol & Med Chem, Chapel Hill, NC USA.
[Gibbons, Simon; Arunotayanun, Warunya] UCL Sch Pharm, Dept Pharmaceut & Biol Chem, London, England.
[Treble, Ric] LGC Forens, London, England.
[Iversen, Les] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England.
RP Iversen, L (reprint author), Univ Oxford, Dept Pharmacol, S Parks Rd, Oxford OX1 3QT, England.
EM les.iversen@pharm.ox.ac.uk
RI Roth, Bryan/F-3928-2010
FU NIMH Psychoactive Drug Screening Program; UK's Forensic Early Warning
System; NIMH-PDSP [HHSN-271-2008-00025-C]
FX Supported by the NIMH Psychoactive Drug Screening Program. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.; Production of analytical
reference standards for 3-methoxy-PCP and 3-methoxy-PCE was funded by
the UK's Forensic Early Warning System and the authors thank the UK Home
Office Centre for Applied Science and Technology for permission to use
these materials in this study. The NIMH-PDSP is supported by Contract #
HHSN-271-2008-00025-C.
NR 26
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U1 0
U2 18
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 MAR 19
PY 2013
VL 8
IS 3
AR e59334
DI 10.1371/journal.pone.0059334
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125SR
UT WOS:000317562100111
PM 23527166
ER
PT J
AU Weiger, MC
Vedham, V
Stuelten, CH
Shou, KR
Herrera, M
Sato, M
Losert, W
Parent, CA
AF Weiger, Michael C.
Vedham, Vidya
Stuelten, Christina H.
Shou, Karen
Herrera, Mark
Sato, Misako
Losert, Wolfgang
Parent, Carole A.
TI Real-Time Motion Analysis Reveals Cell Directionality as an Indicator of
Breast Cancer Progression
SO PLOS ONE
LA English
DT Article
ID LYSOPHOSPHATIDIC ACID RECEPTORS; CARCINOMA-CELLS; MESENCHYMAL
TRANSITION; KINASE INHIBITOR; TYROSINE KINASES; TUMOR-METASTASIS; BONE
METASTASES; PARACRINE LOOP; IN-VITRO; MIGRATION
AB Cancer cells alter their migratory properties during tumor progression to invade surrounding tissues and metastasize to distant sites. However, it remains unclear how migratory behaviors differ between tumor cells of different malignancy and whether these migratory behaviors can be utilized to assess the malignant potential of tumor cells. Here, we analyzed the migratory behaviors of cell lines representing different stages of breast cancer progression using conventional migration assays or time-lapse imaging and particle image velocimetry (PIV) to capture migration dynamics. We find that the number of migrating cells in transwell assays, and the distance and speed of migration in unconstrained 2D assays, show no correlation with malignant potential. However, the directionality of cell motion during 2D migration nicely distinguishes benign and tumorigenic cell lines, with tumorigenic cell lines harboring less directed, more random motion. Furthermore, the migratory behaviors of epithelial sheets observed under basal conditions and in response to stimulation with epidermal growth factor (EGF) or lysophosphatitic acid (LPA) are distinct for each cell line with regard to cell speed, directionality, and spatiotemporal motion patterns. Surprisingly, treatment with LPA promotes a more cohesive, directional sheet movement in lung colony forming MCF10CA1a cells compared to basal conditions or EGF stimulation, implying that the LPA signaling pathway may alter the invasive potential of MCF10CA1a cells. Together, our findings identify cell directionality as a promising indicator for assessing the tumorigenic potential of breast cancer cell lines and show that LPA induces more cohesive motility in a subset of metastatic breast cancer cells.
C1 [Weiger, Michael C.; Vedham, Vidya; Stuelten, Christina H.; Shou, Karen; Parent, Carole A.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Herrera, Mark; Losert, Wolfgang] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
[Sato, Misako] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Parent, CA (reprint author), NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM parentc@mail.nih.gov
FU Center for Cancer Research, NCI, National Institutes of Health; NIH
[R01GM085574]
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, NCI, National Institutes of Health. WL
acknowledges support by NIH grant R01GM085574. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 66
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U1 0
U2 21
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 MAR 19
PY 2013
VL 8
IS 3
AR e58859
DI 10.1371/journal.pone.0058859
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125SR
UT WOS:000317562100052
PM 23527039
ER
PT J
AU Harris, AK
Meyerson, JR
Matsuoka, Y
Kuybeda, O
Moran, A
Bliss, D
Das, SR
Yewdell, JW
Sapiro, G
Subbarao, K
Subramaniam, S
AF Harris, Audray K.
Meyerson, Joel R.
Matsuoka, Yumiko
Kuybeda, Oleg
Moran, Amy
Bliss, Donald
Das, Suman R.
Yewdell, Jonathan W.
Sapiro, Guillermo
Subbarao, Kanta
Subramaniam, Sriram
TI Structure and accessibility of HA trimers on intact 2009 H1N1 pandemic
influenza virus to stem region-specific neutralizing antibodies
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE envelope glycoproteins; subvolume averaging; virus structure;
hemagglutunin; cryo-electron microscopy
ID A VIRUS; CRYOELECTRON TOMOGRAPHY; MONOCLONAL-ANTIBODIES; ELECTRON
TOMOGRAPHY; MEMBRANE-FUSION; HEMAGGLUTININ; EPITOPE; PH; SUBTYPES;
BINDING
AB Rapid antigenic variation of HA, the major virion surface protein of influenza A virus, remains the principal challenge to the development of broader and more effective vaccines. Some regions of HA, such as the stem region proximal to the viral membrane, are nevertheless highly conserved across strains and among most subtypes. A fundamental question in vaccine design is the extent to which HA stem regions on the surface of the virus are accessible to broadly neutralizing antibodies. Here we report 3D structures derived from cryoelectron tomography of HA on intact 2009 H1N1 pandemic virions in the presence and absence of the antibody C179, which neutralizes viruses expressing a broad range of HA subtypes, including H1, H2, H5, H6, and H9. By fitting previously derived crystallographic structures of trimeric HA into the density maps, we deduced the locations of the molecular surfaces of HA involved in interaction with C179. Using computational methods to distinguish individual unliganded HA trimers from those that have bound C179 antibody, we demonstrate that similar to 75% of HA trimers on the surface of the virus have C179 bound to the stem domain. Thus, despite their close packing on the viral membrane, the majority of HA trimers on intact virions are available to bind anti-stem antibodies that target conserved HA epitopes, establishing the feasibility of universal influenza vaccines that elicit such antibodies.
C1 [Harris, Audray K.; Meyerson, Joel R.; Subramaniam, Sriram] NCI, Lab Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Matsuoka, Yumiko; Subbarao, Kanta] NIAID, Labs Infect Dis, NIH, Bethesda, MD 20892 USA.
[Das, Suman R.; Yewdell, Jonathan W.] NIAID, Labs Viral Dis, NIH, Bethesda, MD 20892 USA.
[Kuybeda, Oleg; Moran, Amy; Bliss, Donald] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
[Meyerson, Joel R.] MRC, Mitochondrial Biol Unit, Cambridge CB2 0XY, England.
[Kuybeda, Oleg; Sapiro, Guillermo] Univ Minnesota, Dept Elect & Comp Engn, Minneapolis, MN 55455 USA.
RP Subramaniam, S (reprint author), NCI, Lab Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM ss1@nih.gov
FU National Cancer Institute; National Institute of Allergy and Infectious
Diseases; Department of Defense; NIH Intramural AIDS Research Fellowship
FX We thank S. Fellini and S. Chacko and their colleagues for continued
support of our use of the Biowulf computing cluster at the National
Institutes of Health (NIH) (http://biowulf.nih.gov). This work was
supported by funds from the intramural program of the National Cancer
Institute (to S.S.), the intramural program of the National Institute of
Allergy and Infectious Diseases (to K.S.), the Department of Defense (to
G.S.), and an NIH Intramural AIDS Research Fellowship (to J.R.M.).
NR 50
TC 29
Z9 31
U1 0
U2 24
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 MAR 19
PY 2013
VL 110
IS 12
BP 4592
EP 4597
DI 10.1073/pnas.1214913110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125EK
UT WOS:000317521600045
PM 23460696
ER
PT J
AU Feng, MQ
Gao, W
Wang, RQ
Chen, WZ
Man, YG
Figg, WD
Wang, XW
Dimitrov, DS
Ho, M
AF Feng, Mingqian
Gao, Wei
Wang, Ruoqi
Chen, Weizao
Man, Yan-Gao
Figg, William Douglas
Wang, Xin Wei
Dimitrov, Dimiter S.
Ho, Mitchell
TI Therapeutically targeting glypican-3 via a conformation-specific
single-domain antibody in hepatocellular carcinoma
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE heparan sulfate proteoglycans; liver cancer; monoclonal antibodies;
phage display; cell growth
ID LIVER-CANCER; KINASE MST2; IN-VIVO; GROWTH; PROTEIN; PATHWAY; MARKER;
HIPPO; PROLIFERATION; COMBINATION
AB Glypican-3 (GPC3) has emerged as a candidate therapeutic target in hepatocellular carcinoma (HCC), but the oncogenic role of GPC3 in HCC is poorly understood. Here, we report a human heavy-chain variable domain antibody, HN3, with high affinity (K-d = 0.6 nM) for cell-surface-associated GPC3 molecules. The human antibody recognized a conformational epitope that requires both the amino and carboxy terminal domains of GPC3. HN3 inhibited proliferation of GPC3-positive cells and exhibited significant inhibition of HCC xenograft tumor growth in nude mice. The underlying mechanism of HN3 action may involve cell-cycle arrest at G1 phase through Yes-associated protein signaling. This study suggests a previously unrecognized mechanism for GPC3-targeted cancer therapy.
C1 [Feng, Mingqian; Gao, Wei; Wang, Ruoqi; Ho, Mitchell] NCI, Mol Biol Lab, Bethesda, MD 20892 USA.
[Figg, William Douglas] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Wang, Xin Wei] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA.
[Chen, Weizao; Dimitrov, Dimiter S.] NCI, Frederick Natl Lab, Frederick, MD 21702 USA.
[Man, Yan-Gao] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA.
RP Ho, M (reprint author), NCI, Mol Biol Lab, Bethesda, MD 20892 USA.
EM homi@mail.nih.gov
RI Ho, Mitchell/F-5059-2015; Wang, Xin/B-6162-2009; Figg Sr,
William/M-2411-2016
FU Intramural Research Program, Center for Cancer Research, NCI, NIH [Z01
BC 010891, ZIA BC 010891]
FX We thank Shawn Spencer for calculating the HN3 half-life in vivo; our
colleagues Yen Phung (National Cancer Institute; NCI) for generating the
YP7 mAb and Heungnam Kim (NCI) for establishing the A431/G1 cell line
used in the present project; and the National Institutes of Health (NIH)
Fellows Editorial Board for editorial assistance. This work was
supported by Grants Z01 BC 010891 and ZIA BC 010891 from the Intramural
Research Program, Center for Cancer Research, NCI, NIH (to M.H.).
NR 43
TC 33
Z9 35
U1 3
U2 17
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 MAR 19
PY 2013
VL 110
IS 12
BP E1083
EP E1091
DI 10.1073/pnas.1217868110
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125EK
UT WOS:000317521600004
PM 23471984
ER
PT J
AU Cozen, W
Yu, G
Gail, MH
Ridaura, VK
Nathwani, BN
Hwang, AE
Hamilton, AS
Mack, TM
Gordon, JI
Goedert, JJ
AF Cozen, W.
Yu, G.
Gail, M. H.
Ridaura, V. K.
Nathwani, B. N.
Hwang, A. E.
Hamilton, A. S.
Mack, T. M.
Gordon, J. I.
Goedert, J. J.
TI Fecal microbiota diversity in survivors of adolescent/young adult
Hodgkin lymphoma: a study of twins
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE Hodgkin lymphoma; twin study; survivorship; hygiene hypothesis; human
fecal microbiome
ID GUT MICROBIOME; EARLY-LIFE; DISEASE; CELLS; RISK; IGE
AB Background: Adolescent/young adult Hodgkin lymphoma (AYAHL) survivors report fewer exposures to infections during childhood compared with controls, and they have functional lymphocyte aberrations. The gut microbiota plays a central role in immunity.
Methods: We investigated whether fecal microbial diversity differed between 13 AYAHL survivors and their unaffected co-twin controls. Pyrosequencing of fecal bacterial 16S rRNA amplicons yielded 252 943 edited reads that were assigned to species-level operational taxonomic units (OTUs) and standardised for sequencing depth by random sampling. Microbial diversity was compared within vs between twin pairs and by case-control status.
Results: The number of unique OTUs was more similar within twin pairs compared with randomly paired participants (P = 0.0004). The AYAHL cases had fewer unique OTUs compared with their co-twin controls (338 vs 369, P = 0.015); this difference was not significant (169 vs 183, P = 0.10) when restricted to abundant OTUs.
Conclusion: In this small study, AYAHL survivors appear to have a deficit of rare gut microbes. Further work is needed to determine if reduced microbial diversity is a consequence of the disease, its treatment, or a particularly hygienic environment.
C1 [Cozen, W.; Hwang, A. E.; Hamilton, A. S.; Mack, T. M.] USC Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Cozen, W.; Hamilton, A. S.; Mack, T. M.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA.
[Cozen, W.; Mack, T. M.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90089 USA.
[Yu, G.; Gail, M. H.; Goedert, J. J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Ridaura, V. K.; Gordon, J. I.] Washington Univ, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA.
[Nathwani, B. N.] Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA.
RP Goedert, JJ (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7068, Rockville, MD 20852 USA.
EM goedertj@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute; National
Cancer Institute [1R01CA58839, R03CA110836-01A2, HHSN261201000035C];
Leukemia Lymphoma Society [6137-07]
FX We would like to thank Maureen Cairns for her assistance with data
collection, and the twins for participating in the research. This work
was supported by the Intramural Research Program of the National Cancer
Institute, as well as by grants from the National Cancer Institute
(1R01CA58839 TMM, R03CA110836-01A2 WC, and HHSN261201000035C WC) and the
Leukemia Lymphoma Society (6137-07 WC).
NR 38
TC 6
Z9 6
U1 0
U2 21
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAR 19
PY 2013
VL 108
IS 5
BP 1163
EP 1167
DI 10.1038/bjc.2013.60
PG 5
WC Oncology
SC Oncology
GA 118PQ
UT WOS:000317038100022
PM 23443674
ER
PT J
AU Arem, H
Bobe, G
Sampson, J
Subar, AF
Park, Y
Risch, H
Hollenbeck, A
Mayne, ST
Stolzenberg-Solomon, RZ
AF Arem, H.
Bobe, G.
Sampson, J.
Subar, A. F.
Park, Y.
Risch, H.
Hollenbeck, A.
Mayne, S. T.
Stolzenberg-Solomon, R. Z.
TI Flavonoid intake and risk of pancreatic cancer in the National
Institutes of Health-AARP Diet and Health Study Cohort
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE pancreatic neoplasms; flavonoids; epidemiology; cohort studies
ID RETIRED-PERSONS DIET; AMERICAN-ASSOCIATION; POLYPHENOLS; APOPTOSIS
AB Background: Limited epidemiological studies show inverse associations between dietary flavonoid intake and pancreatic cancer risk, but results are inconsistent and are based on few cases. We examined the association between intake of flavonoids and pancreatic cancer risk in the large, prospective National Institutes of Health-AARP Diet and Health Study Cohort.
Methods: During follow-up through 2006 (median follow-up 10.6 years), 2379 pancreatic cancer cases were identified. We used Cox proportional hazards modelling to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
Results: We found no association between total flavonoid intake (Q5 vs Q1 HR = 1.09, 95% CI: 0.96-1.24) or any flavonoid subtypes and pancreatic cancer risk. Significant interactions were not observed by age, sex, smoking status, BMI or diabetes.
Conclusion: Our results do not support the hypothesis that flavonoids have a protective role in pancreatic cancer carcinogenesis.
C1 [Arem, H.; Risch, H.; Mayne, S. T.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA.
[Arem, H.; Sampson, J.; Park, Y.; Stolzenberg-Solomon, R. Z.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Bobe, G.] Univ Oregon, Linus Pauling Inst, Corvallis, OR USA.
[Subar, A. F.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Risch, H.; Mayne, S. T.] Yale Canc Ctr, New Haven, CT USA.
[Hollenbeck, A.] AARP, Washington, DC USA.
RP Arem, H (reprint author), Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA.
EM Aremhe2@mail.nih.gov
OI Park, Yikyung/0000-0002-6281-489X
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute; [T32 CA105666]
FX This work was supported in part by the pre-doctoral training grant T32
CA105666. This research was also supported in part by the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute. Cancer incidence data from the Atlanta metropolitan area were
collected by the Georgia Center for Cancer Statistics, Department of
Epidemiology, Rollins School of Public Health, Emory University. Cancer
incidence data from California were collected by the California
Department of Health Services, Cancer Surveillance Section. Cancer
incidence data from the Detroit metropolitan area were collected by the
Michigan Cancer Surveillance Program, Community Health Administration,
State of Michigan. The Florida cancer incidence data used in this report
were collected by the Florida Cancer Data System under contract with the
Florida Department of Health. The views expressed herein are solely
those of the authors and do not necessarily reflect those of the
contractor or the Department of Health. Cancer incidence data from
Louisiana were collected by the Louisiana Tumor Registry, Louisiana
State University Medical Center in New Orleans. Cancer incidence data
from New Jersey were collected by the New Jersey State Cancer Registry,
Cancer Epidemiology Services, New Jersey State Department of Health and
Senior Services. Cancer incidence data from North Carolina were
collected by the North Carolina Central Cancer Registry. Cancer
incidence data from Pennsylvania were supplied by the Division of Health
Statistics and Research, Pennsylvania Department of Health, Harrisburg,
Pennsylvania. The Pennsylvania Department of Health specifically
disclaims responsibility for any analyses, interpretations, or
conclusions. Cancer incidence data from Arizona were collected by the
Arizona Cancer Registry, Division of Public Health Services, Arizona
Department of Health Services. Cancer incidence data from Texas were
collected by the Texas Cancer Registry, Cancer Epidemiology and
Surveillance Branch, Texas Department of State Health Services. Cancer
incidence data from Nevada were collected by the Nevada Central Cancer
Registry, Center for Health Data and Research, Bureau of Health Planning
and Statistics, State Health Division, State of Nevada Department of
Health and Human Services. We also thank Sigurd Hermansen and Kerry
Grace Morrissey from Westat for ascertainment and management of study
outcomes, and Leslie Carroll at Information Management Services for data
support and analysis.
NR 20
TC 6
Z9 6
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAR 19
PY 2013
VL 108
IS 5
BP 1168
EP 1172
DI 10.1038/bjc.2012.584
PG 5
WC Oncology
SC Oncology
GA 118PQ
UT WOS:000317038100023
PM 23299536
ER
PT J
AU Wilson, JC
Murray, LJ
Hughes, CM
Black, A
Anderson, LA
AF Wilson, J. C.
Murray, L. J.
Hughes, C. M.
Black, A.
Anderson, L. A.
TI Non-steroidal anti-inflammatory drug and aspirin use and the risk of
head and neck cancer
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE head and neck cancer; ibuprofen; aspirin; cohort study
ID UPPER AERODIGESTIVE TRACT; ORAL-CANCER; CYCLOOXYGENASE-2; INHIBITION;
PREVENTION; COHORT; COX-2
AB Background: Evidence for non-steroidal anti-inflammatory drugs (NSAIDs) preventing head and neck cancer (HNC) is inconclusive; however, there is some suggestion that aspirin may exert a protective effect.
Methods: Using data from the United States National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we examined the association between aspirin and ibuprofen use and HNC.
Results: Regular aspirin use was associated with a significant 22% reduction in HNC risk. No association was observed with regular ibuprofen use.
Conclusion: Aspirin may have potential as a chemopreventive agent for HNC, but further investigation is warranted.
C1 [Wilson, J. C.; Murray, L. J.; Anderson, L. A.] Queens Univ Belfast, Inst Clin Sci, Sch Med Dent & Biomed Sci, Ctr Publ Hlth,RVH, Belfast BT12 6BJ, Antrim, North Ireland.
[Hughes, C. M.] Queens Univ Belfast, Sch Pharm, Ctr Med Biol, Belfast BT9 7BL, Antrim, North Ireland.
[Black, A.] NCI, Rockville, MD 20852 USA.
RP Wilson, JC (reprint author), Queens Univ Belfast, Inst Clin Sci, Sch Med Dent & Biomed Sci, Ctr Publ Hlth,RVH, Block B,Grosvenor Rd, Belfast BT12 6BJ, Antrim, North Ireland.
EM wilsonj@uhbs.ch
OI Anderson, Lesley/0000-0002-1000-3649
FU Division of Cancer Prevention, National Cancer Institute; NIH, DHHS
FX This research was supported by contracts from the Division of Cancer
Prevention, National Cancer Institute; NIH, DHHS. We thank Drs Christine
Berg and Philip Prorok, Division of Cancer Prevention, National Cancer
Institute, the Screening Centre investigators and staff of the PLCO
Cancer Screening Trial; Mr Tom Riley and staff, Information Management
Services, Inc.; Ms Barbara O'Brien and staff, Westat, Inc. Most
importantly, we acknowledge the study participants for their
contributions to making this study possible.
NR 22
TC 8
Z9 9
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAR 19
PY 2013
VL 108
IS 5
BP 1178
EP 1181
DI 10.1038/bjc.2013.73
PG 4
WC Oncology
SC Oncology
GA 118PQ
UT WOS:000317038100025
PM 23449358
ER
PT J
AU Lubin, JH
Caporaso, NE
AF Lubin, J. H.
Caporaso, N. E.
TI Misunderstandings in the misconception on the use of pack-years in
analysis of smoking
SO BRITISH JOURNAL OF CANCER
LA English
DT Letter
ID LUNG-CANCER MORTALITY; CIGARETTE-SMOKING; TOTAL EXPOSURE;
ALCOHOL-CONSUMPTION; BLADDER-CANCER; ODDS RATIOS; INTENSITY; DNA; RISK;
REPAIR
C1 [Lubin, J. H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Caporaso, N. E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
RP Lubin, JH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8105, Rockville, MD 20852 USA.
EM lubinj@exchange.nih.gov
NR 23
TC 4
Z9 4
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAR 19
PY 2013
VL 108
IS 5
BP 1218
EP 1220
DI 10.1038/bjc.2013.76
PG 3
WC Oncology
SC Oncology
GA 118PQ
UT WOS:000317038100033
PM 23449359
ER
PT J
AU Sidorova, NY
Scott, T
Rau, DC
AF Sidorova, Nina Y.
Scott, Thomas
Rau, Donald C.
TI DNA Concentration-Dependent Dissociation of EcoRI: Direct Transfer or
Reaction during Hopping
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID DIFFUSION-DRIVEN MECHANISMS; ONE-DIMENSIONAL DIFFUSION;
RESTRICTION-ENDONUCLEASE; NONSPECIFIC DNA; PROTEIN TRANSLOCATION;
INTERSEGMENT TRANSFER; NUCLEIC-ACIDS; COGNATE SITES; WATER RELEASE;
BINDING
AB Direct transfer of proteins between DNA helices is a recognized important feature of the recognition site search process. Direct transfer is characterized by a dissociation rate that depends on total DNA concentration. This is taken as evidence for the formation of an intermediate DNA-protein-DNA ternary complex. We find that the dissociation rate of EcoRI-DNA-specific complexes at 80 mM NaCl depends on the concentration of competitor oligonucleotide suggesting that direct transfer contributes to EcoRI dissociation. This dependence on competitor DNA concentration is not seen at 180 mM salt. A careful examination of the salt concentration dependence of the dissociation rate, however, shows that the predictions for the formation of a ternary complex are not observed experimentally. The findings can be rationalized by considering that just after dissociating from a DNA fragment the protein remains in close proximity to that fragment, can reassociate with it, and diffuse back to the recognition site rather than bind to an oligonucleotide in solution, a hopping excursion. The probability that a protein will bind to an oligonucleotide during a hop can be approximately calculated and shown to explain the data. A dependence of the dissociation rate of a DNA-protein complex on competitor DNA concentration does not necessarily mean direct transfer.
C1 [Sidorova, Nina Y.; Scott, Thomas; Rau, Donald C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
RP Rau, DC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
EM raud@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health; NICHD
(Eunice Kennedy Shriver National Institute of Child Health and Human
Development)
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, NICHD (Eunice Kennedy Shriver National
Institute of Child Health and Human Development).
NR 40
TC 13
Z9 13
U1 2
U2 12
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 MAR 19
PY 2013
VL 104
IS 6
BP 1296
EP 1303
DI 10.1016/j.bpj.2013.01.041
PG 8
WC Biophysics
SC Biophysics
GA 111MO
UT WOS:000316525600014
PM 23528089
ER
PT J
AU Ghuman, AS
van den Honert, RN
Martin, A
AF Ghuman, Avniel Singh
van den Honert, Rebecca N.
Martin, Alex
TI Interregional neural synchrony has similar dynamics during spontaneous
and stimulus-driven states
SO SCIENTIFIC REPORTS
LA English
DT Article
ID RESTING HUMAN BRAIN; FUNCTIONAL ARCHITECTURE; CORTICAL ACTIVITY;
AUDITORY-CORTEX; PHASE-LOCKING; MOTOR CORTEX; OSCILLATIONS; EEG; MEG;
FLUCTUATIONS
AB Assessing the correspondence between spontaneous and stimulus-driven neural activity can reveal intrinsic properties of the brain. Recent studies have demonstrated that many large-scale functional networks have a similar spatial structure during spontaneous and stimulus-driven states. However, it is unknown whether the temporal dynamics of network activity are also similar across these states. Here we demonstrate that, in the human brain, interhemispheric coupling of somatosensory regions is preferentially synchronized in the high beta frequency band (similar to 20-30 Hz) in response to somatosensory stimulation and interhemispheric coupling of auditory cortices is preferentially synchronized in the alpha frequency band (similar to 7-12 Hz) in response to auditory stimulation. Critically, these stimulus-driven synchronization frequencies were also selective to these interregional interactions during spontaneous activity. This similarity between stimulus-driven and spontaneous states suggests that frequency-specific oscillatory dynamics are intrinsic to the interactions between the nodes of these brain networks.
C1 [Ghuman, Avniel Singh; van den Honert, Rebecca N.; Martin, Alex] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Ghuman, AS (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
EM ghumana@upmc.edu
OI Ghuman, Avniel/0000-0003-1746-4656
FU NIMH-DIRP
FX We thank Jonathan McDaniel for assistance with data collection, Steve
Gotts, Dale Stevens, David Leopold, and Alex Maier for insightful
comments, and Tom Holroyd and the staff NIMH MEG core for assistance
with data collection. This work was supported by the NIMH-DIRP.
NR 58
TC 2
Z9 2
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD MAR 19
PY 2013
VL 3
AR 1481
DI 10.1038/srep01481
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107WG
UT WOS:000316250900002
PM 23512004
ER
PT J
AU Bhatt, S
Lam, TT
Lycett, SJ
Brown, AJL
Bowden, TA
Holmes, EC
Guan, Y
Wood, JLN
Brown, IH
Kellam, P
Pybus, OG
AF Bhatt, S.
Lam, T. T.
Lycett, S. J.
Brown, A. J. Leigh
Bowden, T. A.
Holmes, E. C.
Guan, Y.
Wood, J. L. N.
Brown, I. H.
Kellam, P.
Pybus, O. G.
CA Combating Swine Influenza
TI The evolutionary dynamics of influenza A virus adaptation to mammalian
hosts
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE influenza; swine; avian; adaptation; genomics; zoonosis
ID MOLECULAR-BASIS; UNITED-STATES; SWINE VIRUS; PIGS; TRANSMISSION; H1N1;
SEQUENCE; HEMAGGLUTININS; EMERGENCE; EPIDEMIC
AB ew questions on infectious disease are more important than understanding how and why avian influenza A viruses successfully emerge in mammalian populations, yet little is known about the rate and nature of the virus' genetic adaptation in new hosts. Here, we measure, for the first time, the genomic rate of adaptive evolution of swine influenza viruses (SwIV) that originated in birds. By using a curated dataset of more than 24 000 human and swine influenza gene sequences, including 41 newly characterized genomes, we reconstructed the adaptive dynamics of three major SwIV lineages (Eurasian, EA; classical swine, CS; triple reassortant, TR). We found that, following the transfer of the EA lineage from birds to swine in the late 1970s, EA virus genes have undergone substantially faster adaptive evolution than those of the CS lineage, which had circulated among swine for decades. Further, the adaptation rates of the EA lineage antigenic haemagglutinin and neuraminidase genes were unexpectedly high and similar to those observed in human influenza A. We show that the successful establishment of avian influenza viruses in swine is associated with raised adaptive evolution across the entire genome for many years after zoonosis, reflecting the contribution of multiple mutations to the coordinated optimization of viral fitness in a new environment. This dynamics is replicated independently in the polymerase genes of the TR lineage, which established in swine following separate transmission from non-swine hosts.
C1 [Bhatt, S.; Lam, T. T.; Pybus, O. G.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
[Bhatt, S.; Kellam, P.] Wellcome Trust Sanger Inst, Hinxton, England.
[Lycett, S. J.; Brown, A. J. Leigh] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland.
[Bowden, T. A.] Univ Oxford, Wellcome Trust Ctr Human Genet, Div Struct Biol, Oxford, England.
[Holmes, E. C.] Penn State Univ, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA.
[Holmes, E. C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Guan, Y.] Univ Hong Kong, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China.
[Wood, J. L. N.] Univ Cambridge, Cambridge Infect Dis Consortium, Cambridge, England.
[Brown, I. H.] Anim Hlth & Vet Labs Agcy, Weybridge, Surrey, England.
RP Pybus, OG (reprint author), Univ Oxford, Dept Zool, S Parks Rd, Oxford OX1 3PS, England.
EM oliver.pybus@zoo.ox.ac.uk
RI Wood, James/A-1626-2008; Lam, Tommy Tsan-Yuk/D-4837-2012; Brown,
Ian/E-1119-2011; APHA, Staff publications/E-6082-2010;
OI Wood, James/0000-0002-0258-3188; Holmes, Edward/0000-0001-9596-3552;
Bowden, Thomas/0000-0002-8066-8785; Pybus, Oliver/0000-0002-8797-2667;
Nguyen-Van-Tam, Jonathan/0000-0003-2579-4655; Lycett,
Samantha/0000-0003-3159-596X; Donnelly, Christl/0000-0002-0195-2463
FU UK COSI [BB/H014306/1]; BBSRC; MRC; Wellcome Trust; Defra [ED1204];
Royal Society; ESNIP3; COSI; Alborada Trust; Science and Technology
Directorate, Department of Homeland Security; Fogarty International
Center, NIH; European Union
FX Combating Swine Influenza Consortium (COSI) members are listed in the
electronic supplementary material. We thank the institutes named in
Material and methods for providing isolates, contributors to ESNIP for
depositing samples and Dr K. van Reeth for facilitating access. This
work was supported by UK COSI (BB/H014306/1), co-funded by BBSRC, MRC,
the Wellcome Trust and Defra. Surveillance in GB pigs was supported by
Defra (ED1204). O.G.P. was supported by the Royal Society and ESNIP3;
S.J.L. by the BBSRC, the Wellcome Trust and COSI; T. A. B. by the
Wellcome Trust; J.L.N.W. by the Alborada Trust and the RAPIDD programme
of the Science and Technology Directorate, Department of Homeland
Security and Fogarty International Center, NIH. ESNIP is funded by the
European Union.
NR 41
TC 13
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U1 7
U2 97
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD MAR 19
PY 2013
VL 368
IS 1614
AR 20120382
DI 10.1098/rstb.2012.0382
PG 8
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 088DH
UT WOS:000314813500018
PM 23382435
ER
PT J
AU Duke-Sylvester, SM
Biek, R
Real, LA
AF Duke-Sylvester, Scott M.
Biek, Roman
Real, Leslie A.
TI Molecular evolutionary signatures reveal the role of host ecological
dynamics in viral disease emergence and spread
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE disease ecology; evolution; phylodynamics; phylogeography; rabies;
dispersal
ID HUMAN-IMMUNODEFICIENCY-VIRUS; DEVELOPING-COUNTRIES; POPULATION-DYNAMICS;
EPIZOOTIC RABIES; RACCOON RABIES; UNITED-STATES; SEQUENCES; EPIDEMIC;
HISTORY; HEALTH
AB RNA viruses account for numerous emerging and perennial infectious diseases, and are characterized by rapid rates of molecular evolution. The ecological dynamics of most emerging RNA viruses are still poorly understood and difficult to ascertain. The availability of genome sequence data for many RNA viruses, in principle, could be used to infer ecological dynamics if changes in population numbers produced a lasting signature within the pattern of genome evolution. As a result, the rapidly emerging phylogeographic structure of a pathogen, shaped by the rise and fall in the number of infections and their spatial distribution, could be used as a surrogate for direct ecological assessments. Based on rabies virus as our example, we use a model combining ecological and evolutionary processes to test whether variation in the rate of host movement results in predictive diagnostic patterns of pathogen genetic structure. We identify several linearizable relationships between host dispersal rate and measures of phylogenetic structure suggesting genetic information can be used to directly infer ecological process. We also find phylogenetic structure may be more revealing than demography for certain ecological processes. Our approach extends the reach of current analytic frameworks for infectious disease dynamics by linking phylogeography back to underlying ecological processes.
C1 [Duke-Sylvester, Scott M.] Univ Louisiana Lafayette, Dept Biol, Lafayette, LA 70506 USA.
[Duke-Sylvester, Scott M.; Real, Leslie A.] Emory Univ, Ctr Dis Ecol, Atlanta, GA 30322 USA.
[Real, Leslie A.] Emory Univ, Dept Biol, Atlanta, GA 30322 USA.
[Biek, Roman] Univ Glasgow, MRC, Ctr Virus Res, Glasgow G12 8QQ, Lanark, Scotland.
[Biek, Roman] Univ Glasgow, Inst Biodivers, Glasgow G12 8QQ, Lanark, Scotland.
[Biek, Roman] Univ Glasgow, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland.
[Real, Leslie A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Real, LA (reprint author), Emory Univ, Ctr Dis Ecol, Atlanta, GA 30322 USA.
EM lreal@emory.edu
OI Biek, Roman/0000-0003-3471-5357
FU NIH [RO1 AI047498]; RAPIDD Programme of the Science and Technology
Directorate, The Department of Homeland Security and The Fogarty
International Center; National Institutes of Health; Louisiana Board of
Regents [LEQSF(2011-14-RD-A-27)]
FX The authors thank Vijay Panjeti and Derek Johnson for their comments.
This research was supported by NIH grant no. RO1 AI047498 to L. A. R.,
and the RAPIDD Programme of the Science and Technology Directorate, The
Department of Homeland Security and The Fogarty International Center,
National Institutes of Health and the Louisiana Board of Regents grant
no. LEQSF(2011-14-RD-A-27) to S. M. D. Computer simulations were
performed on the Emory High Performance Computer Cluster and the
Louisiana Optical Network Initiative computers.
NR 62
TC 3
Z9 3
U1 2
U2 62
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD MAR 19
PY 2013
VL 368
IS 1614
AR 20120194
DI 10.1098/rstb.2012.0194
PG 11
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 088DH
UT WOS:000314813500002
PM 23382419
ER
PT J
AU Faria, NR
Suchard, MA
Rambaut, A
Streicker, DG
Lemey, P
AF Faria, Nuno Rodrigues
Suchard, Marc A.
Rambaut, Andrew
Streicker, Daniel G.
Lemey, Philippe
TI Simultaneously reconstructing viral cross-species transmission history
and identifying the underlying constraints
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE Bayesian diffusion models; branch partitioning; cross-species
transmission; rabies virus
ID RABIES VIRUS; STATISTICAL PHYLOGENETICS; POPULATION-DYNAMICS;
INFECTIOUS-DISEASES; EMERGENCE; EVOLUTION; BATS; ORIGINS; INTERFACE;
PATHOGENS
AB The factors that determine the origin and fate of cross-species transmission events remain unclear for the majority of human pathogens, despite being central for the development of predictive models and assessing the efficacy of prevention strategies. Here, we describe a flexible Bayesian statistical framework to reconstruct virus transmission between different host species based on viral gene sequences, while simultaneously testing and estimating the contribution of several potential predictors of cross-species transmission. Specifically, we use a generalized linear model extension of phylogenetic diffusion to perform Bayesian model averaging over candidate predictors. By further extending this model with branch partitioning, we allow for distinct host transition processes on external and internal branches, thus discriminating between recent cross-species transmissions, many of which are likely to result in dead-end infections, and host shifts that reflect successful onwards transmission in the new host species. Our approach corroborates genetic distance between hosts as a key determinant of both host shifts and cross-species transmissions of rabies virus in North American bats. Furthermore, our results indicate that geographical range overlap is a modest predictor for cross-species transmission, but not for host shifts. Although our evolutionary framework focused on the multi-host reservoir dynamics of bat rabies virus, it is applicable to other pathogens and to other discrete state transition processes.
C1 [Faria, Nuno Rodrigues; Lemey, Philippe] Katholieke Univ Leuven, Dept Microbiol & Immunol, Rega Inst, Louvain, Belgium.
[Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA.
[Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
[Suchard, Marc A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA.
[Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland.
[Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Streicker, Daniel G.] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA.
RP Faria, NR (reprint author), Katholieke Univ Leuven, Dept Microbiol & Immunol, Rega Inst, Louvain, Belgium.
EM nuno.faria@rega.kuleuven.be
RI Faria, Nuno/I-2975-2012;
OI Faria, Nuno/0000-0001-8839-2798; Rodrigues Faria,
Nuno/0000-0002-9747-8822; Rambaut, Andrew/0000-0003-4337-3707
FU European Union [278433-PREDEMICS]; ERC [260864]; US National Science
Foundation [DMS 0856099]; US National Institutes of Health [R01
GM086887, R01 HG006139]; Fundacao para a Ciencia e Tecnologia
[SFRH/BD/64530/2009]; National Evolutionary Synthesis Center (NESCent),
NSF [EF-0423641]; Wellcome Trust [WT092807MA]
FX We are grateful to two anonymous reviewers for their helpful comments.
The research leading to these results has received funding from the
European Union Seventh Framework Programme (FP7/2007-2013) under grant
agreement no. 278433-PREDEMICS and ERC grant agreement no. 260864, the
US National Science Foundation (DMS 0856099) and the US National
Institutes of Health (R01 GM086887 and R01 HG006139). N.R.F. is
supported by Fundacao para a Ciencia e Tecnologia under grant agreement
no. SFRH/BD/64530/2009. This work was facilitated by the participation
of D. G. S. and P. L. in the 2010 RAPIDD Workshop on Cross-species
Transmission, hosted by the National Institutes of Health. Collaboration
between M. A. S., A. R. and P. L. was supported by the National
Evolutionary Synthesis Center (NESCent), NSF EF-0423641. A. R. is
supported by the Wellcome Trust (WT092807MA). Further, research was
partially completed while M. A. S. and P. L. were visiting the Institute
for Mathematical Sciences, National University of Singapore in 2011.
NR 44
TC 31
Z9 31
U1 0
U2 41
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 MAR 19
PY 2013
VL 368
IS 1614
AR 20120196
DI 10.1098/rstb.2012.0196
PG 9
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 088DH
UT WOS:000314813500003
PM 23382420
ER
PT J
AU Hay, SI
Battle, KE
Pigott, DM
Smith, DL
Moyes, CL
Bhatt, S
Brownstein, JS
Collier, N
Myers, MF
George, DB
Gething, PW
AF Hay, Simon I.
Battle, Katherine E.
Pigott, David M.
Smith, David L.
Moyes, Catherine L.
Bhatt, Samir
Brownstein, John S.
Collier, Nigel
Myers, Monica F.
George, Dylan B.
Gething, Peter W.
TI Global mapping of infectious disease
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Review
DE surveillance; biosurveillance; cartography; public health; atlas;
crowdsourcing
ID DOMINANT ANOPHELES VECTORS; MODEL-BASED GEOSTATISTICS; DISTRIBUTION
MAPS; BIONOMIC PRECIS; HUMAN MALARIA; PLASMODIUM-FALCIPARUM; POPULATION
BIOLOGY; HOST-RANGE; TRANSMISSION; HEALTH
AB The primary aim of this review was to evaluate the state of knowledge of the geographical distribution of all infectious diseases of clinical significance to humans. A systematic review was conducted to enumerate cartographic progress, with respect to the data available for mapping and the methods currently applied. The results helped define the minimum information requirements for mapping infectious disease occurrence, and a quantitative framework for assessing the mapping opportunities for all infectious diseases. This revealed that of 355 infectious diseases identified, 174 (49%) have a strong rationale for mapping and of these only 7 (4%) had been comprehensively mapped. A variety of ambitions, such as the quantification of the global burden of infectious disease, international biosurveillance, assessing the likelihood of infectious disease outbreaks and exploring the propensity for infectious disease evolution and emergence, are limited by these omissions. An overview of the factors hindering progress in disease cartography is provided. It is argued that rapid improvement in the landscape of infectious diseases mapping can be made by embracing non-conventional data sources, automation of geo-positioning and mapping procedures enabled by machine learning and information technology, respectively, in addition to harnessing labour of the volunteer 'cognitive surplus' through crowdsourcing.
C1 [Hay, Simon I.; Battle, Katherine E.; Pigott, David M.; Moyes, Catherine L.; Bhatt, Samir; Myers, Monica F.; Gething, Peter W.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
[Hay, Simon I.; Smith, David L.; George, Dylan B.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, Baltimore, MD USA.
[Brownstein, John S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Brownstein, John S.] Boston Childrens Hosp, Childrens Hosp Informat Program, Boston, MA USA.
[Collier, Nigel] Res Org Informat & Syst, Natl Inst Informat, Tokyo, Japan.
RP Hay, SI (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, S Parks Rd, Oxford OX1 3PS, England.
EM simon.hay@zoo.ox.ac.uk
RI Smith, David/L-8850-2013; Hay, Simon/F-8967-2015;
OI Moyes, Catherine/0000-0002-8028-4079; Smith, David/0000-0003-4367-3849;
Hay, Simon/0000-0002-0611-7272; Pigott, David/0000-0002-6731-4034;
Collier, Nigel/0000-0002-7230-4164; Gething, Peter/0000-0001-6759-5449;
Battle, Katherine/0000-0003-2401-2615
FU Wellcome Trust [095066]; Science & Technology Directorate, Department of
Homeland Security; Fogarty International Center, National Institutes of
Health; Wellcome Trust, UK
FX The catalyst for this review was a National Institute for Mathematical
and Biological Synthesis (NIMBioS) and the US Department of Defense
hosted meeting on infectious disease modelling (23-25 January 2011,
Knoxville, TN, USA). NIMBioS also provided K. E. B. with resources to
conduct the literature review. S. I. H. is financially supported by a
Senior Research Fellowship from the Wellcome Trust (no. 095066) which
also supports P. W. G., K. E. B. and D. M. P.; S. I. H., D. L. S. and D.
B. G. also acknowledge support from the RAPIDD programme of the Science
& Technology Directorate, Department of Homeland Security, and the
Fogarty International Center, National Institutes of Health
(http://www.fic.nih.gov). This work also forms part of the output of the
Malaria Atlas Project (MAP, http://www.map.ox.ac.uk), principally
financially supported by the Wellcome Trust, UK
(http://www.wellcome.ac.uk). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript. Thanks are extended to Dr Kevin Hanson and Prof. Louis Gross
for insightful comments, to the Global Infectious Diseases and
Epidemiology Network (GIDEON) for permission to reproduce their data
within the 355 maps of the supplementary material. Finally, we are
grateful to the editors Dr Oliver Pybus, Prof. Christophe Fraser and
Prof. Andrew Rambaut for inviting us to participate in the scientific
discussion meeting.
NR 111
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Z9 44
U1 2
U2 127
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 MAR 19
PY 2013
VL 368
IS 1614
AR 20120250
DI 10.1098/rstb.2012.0250
PG 11
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 088DH
UT WOS:000314813500014
PM 23382431
ER
PT J
AU Park, M
Loverdo, C
Schreiber, SJ
Lloyd-Smith, JO
AF Park, Miran
Loverdo, Claude
Schreiber, Sebastian J.
Lloyd-Smith, James O.
TI Multiple scales of selection influence the evolutionary emergence of
novel pathogens
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE emerging diseases; pathogen evolution; adaptation; branching processes
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CROSS-SPECIES TRANSMISSION; WITHIN-HOST;
INFECTIOUS-DISEASES; MOLECULAR EVOLUTION; VIRAL LOAD; RNA VIRUS;
DYNAMICS; ADAPTATION; VIRULENCE
AB When pathogens encounter a novel environment, such as a new host species or treatment with an antimicrobial drug, their fitness may be reduced so that adaptation is necessary to avoid extinction. Evolutionary emergence is the process by which new pathogen strains arise in response to such selective pressures. Theoretical studies over the last decade have clarified some determinants of emergence risk, but have neglected the influence of fitness on evolutionary rates and have not accounted for the multiple scales at which pathogens must compete successfully. We present a cross-scale theory for evolutionary emergence, which embeds a mechanistic model of within-host selection into a stochastic model for emergence at the population scale. We explore how fitness landscapes at within-host and between-host scales can interact to influence the probability that a pathogen lineage will emerge successfully. Results show that positive correlations between fitnesses across scales can greatly facilitate emergence, while cross-scale conflicts in selection can lead to evolutionary dead ends. The local genotype space of the initial strain of a pathogen can have disproportionate influence on emergence probability. Our cross-scale model represents a step towards integrating laboratory experiments with field surveillance data to create a rational framework to assess emergence risk.
C1 [Park, Miran; Loverdo, Claude; Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
[Schreiber, Sebastian J.] Univ Calif Davis, Dept Evolut & Ecol, Davis, CA 95616 USA.
[Schreiber, Sebastian J.] Univ Calif Davis, Grad Grp Appl Math, Davis, CA 95616 USA.
[Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Park, M (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, 610 Charles E Young Dr S, Los Angeles, CA 90095 USA.
EM miran.park@ucla.edu
RI Lloyd-Smith, James/K-4080-2012;
OI Lloyd-Smith, James/0000-0001-7941-502X; Loverdo,
Claude/0000-0002-0888-1717
FU NSF [EF-0928690, EF-0928987]; De Logi Chair in Biological Sciences;
Science and Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health; NIGMS
[T32GM008185]
FX The authors would like to thank John Novembre and members of the
Lloyd-Smith laboratory for helpful suggestions and comments. The project
was supported by the NSF grant nos EF-0928690 and EF-0928987. J.L.S.
acknowledges the support of the De Logi Chair in Biological Sciences,
and the RAPIDD program of the Science and Technology Directorate,
Department of Homeland Security, and the Fogarty International Center,
National Institutes of Health. M. P. was also supported by NIGMS grant
no. T32GM008185. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the National
Institute of General Medical Sciences or the National Institutes of
Health.
NR 63
TC 16
Z9 16
U1 3
U2 57
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD MAR 19
PY 2013
VL 368
IS 1614
AR 20120333
DI 10.1098/rstb.2012.0333
PG 13
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 088DH
UT WOS:000314813500016
PM 23382433
ER
PT J
AU Viboud, C
Nelson, MI
Tan, Y
Holmes, EC
AF Viboud, Cecile
Nelson, Martha I.
Tan, Yi
Holmes, Edward C.
TI Contrasting the epidemiological and evolutionary dynamics of influenza
spatial transmission
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Review
DE influenza; spatial diffusion; human mobility; phylogeography; source
population; viral persistence
ID WHOLE-GENOME ANALYSIS; UNITED-STATES; PANDEMIC INFLUENZA; A VIRUS;
METAPOPULATION DYNAMICS; INTERNATIONAL SPREAD; GEOGRAPHIC SPREAD; H1N1
INFLUENZA; GLOBAL SPREAD; H3N2 VIRUSES
AB In the past decade, rapid increases in the availability of high-resolution molecular and epidemiological data, combined with developments in statistical and computational methods to simulate and infer migration patterns, have provided key insights into the spatial dynamics of influenza A viruses in humans. In this review, we contrast findings from epidemiological and molecular studies of influenza virus transmission at different spatial scales. We show that findings are broadly consistent in large-scale studies of inter-regional or inter-hemispheric spread in temperate regions, revealing intense epidemics associated with multiple viral introductions, followed by deep troughs driven by seasonal bottlenecks. However, aspects of the global transmission dynamics of influenza viruses are still debated, especially with respect to the existence of tropical source populations experiencing high levels of genetic diversity and the extent of prolonged viral persistence between epidemics. At the scale of a country or community, epidemiological studies have revealed spatially structured diffusion patterns in seasonal and pandemic outbreaks, which were not identified in molecular studies. We discuss the role of sampling issues in generating these conflicting results, and suggest strategies for future research that may help to fully integrate the epidemiological and evolutionary dynamics of influenza virus over space and time.
C1 [Viboud, Cecile; Nelson, Martha I.; Tan, Yi; Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
RP Viboud, C (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM viboudc@mail.nih.gov
OI Holmes, Edward/0000-0001-9596-3552
FU Division of International Epidemiology and Population Studies, Fogarty
International Center, National Institutes of Health; International
Influenza Unit, Office of Global Affairs, Department of Health and Human
Services
FX This research was conducted in the context of the MISMS Study, an
ongoing international collaborative effort to understand influenza
epidemiological and evolutionary patterns, led by the Fogarty
International Center, National Institutes of Health
(http://www.origem.info/misms/index.php). This work was supported by the
in-house Influenza Research Program of the Division of International
Epidemiology and Population Studies, Fogarty International Center,
National Institutes of Health, which is funded by the International
Influenza Unit, Office of Global Affairs, Department of Health and Human
Services. All authors: no reported conflicts.
NR 89
TC 17
Z9 17
U1 2
U2 50
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD MAR 19
PY 2013
VL 368
IS 1614
AR 20120199
DI 10.1098/rstb.2012.0199
PG 9
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 088DH
UT WOS:000314813500005
PM 23382422
ER
PT J
AU Yuan, HY
Koelle, K
AF Yuan, Hsiang-Yu
Koelle, Katia
TI The evolutionary dynamics of receptor binding avidity in influenza A: a
mathematical model for a new antigenic drift hypothesis
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE influenza evolution; antigenic drift; binding avidity changes; disease
dynamics
ID IMMUNIZATION PRACTICES ACIP; HEMAGGLUTININ ANTIBODIES;
ADVISORY-COMMITTEE; GENETIC EVOLUTION; CROSS-IMMUNITY; VIRUS; SELECTION;
HA; RECOMMENDATIONS; DETERMINANTS
AB The most salient feature of influenza evolution in humans is its antigenic drift. This process is characterized by structural changes in the virus's B-cell epitopes and ultimately results in the ability of the virus to evade immune recognition and thereby reinfect previously infected hosts. Until recently, amino acid substitutions in epitope regions of the viral haemagglutinin were thought to be positively selected for their ability to reduce antibody binding and therefore were thought to be responsible for driving antigenic drift. However, a recent hypothesis put forward by Hensley and co-workers posits that cellular receptor binding avidity is the dominant phenotype under selection, with antigenic drift being a side effect of these binding avidity changes. Here, we present a mathematical formulation of this new antigenic drift model and use it to show how rates of antigenic drift depend on epidemiological parameters. We further use the model to evaluate how two different vaccination strategies can impact antigenic drift rates and ultimately disease incidence levels. Finally, we discuss the assumptions present in the model formulation, predictions of the model, and future work that needs to be done to determine the consistency of this hypothesis with known patterns of influenza's genetic and antigenic evolution.
C1 [Yuan, Hsiang-Yu] Duke Univ, Program Computat Biol & Bioinformat, Durham, NC 27708 USA.
[Yuan, Hsiang-Yu; Koelle, Katia] Duke Univ, Dept Biol, Durham, NC 27708 USA.
[Koelle, Katia] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Yuan, HY (reprint author), Duke Univ, Program Computat Biol & Bioinformat, Durham, NC 27708 USA.
EM hy.yuan@duke.edu; katia.koelle@duke.edu
FU RAPIDD programme of the Science and Technology Directorate, Department
of Homeland Security [NSF-EF-08-27416]; Fogarty International Centre;
James S. McDonnell Foundation
FX We thank Christophe Fraser, Oliver Pybus and Andrew Rambaut for the
opportunity to present this work at the 2012 Royal Society Meeting
'Next-generation molecular and evolutionary epidemiology of infectious
disease'. We also thank the participants of this meeting, two anonymous
referees, members of the Koelle research group, and Ben Bolker for
helpful comments and useful discussions. This work was supported by
grant no. NSF-EF-08-27416 to K. K., by the RAPIDD programme of the
Science and Technology Directorate, Department of Homeland Security, and
the Fogarty International Centre, and by a Complex Systems grant to K.
K. from the James S. McDonnell Foundation.
NR 41
TC 5
Z9 5
U1 0
U2 26
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD MAR 19
PY 2013
VL 368
IS 1614
AR 20120204
DI 10.1098/rstb.2012.0204
PG 11
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 088DH
UT WOS:000314813500009
PM 23382426
ER
PT J
AU Sastalla, I
Crown, D
Masters, SL
McKenzie, A
Leppla, SH
Moayeri, M
AF Sastalla, Inka
Crown, Devorah
Masters, Seth L.
McKenzie, Andrew
Leppla, Stephen H.
Moayeri, Mahtab
TI Transcriptional analysis of the three Nlrp1 paralogs in mice
SO BMC GENOMICS
LA English
DT Article
DE Nlrp1; Inflammasome; Anthrax toxins; Lethal toxin; Bacillus anthracis;
Splice variants
ID ANTHRAX LETHAL TOXIN; INFLAMMASOME ACTIVATION; SUSCEPTIBILITY;
MACROPHAGES; PYROPTOSIS; RECEPTORS; GENES; FLIP
AB Background: Signals of danger and damage in the cytosol of cells are sensed by NOD-like receptors (NLRs), which are components of multiprotein complexes called inflammasomes. Inflammasomes activate caspase-1, resulting in IL-1-beta and IL-18 secretion and an inflammatory response. To date, the only known activator of rodent Nlrp1 is anthrax lethal toxin (LT), a protease secreted by the bacterial pathogen Bacillus anthracis. Although susceptibility of mouse macrophages to LT has been genetically linked to Nlrp1b, mice harbor two additional Nlrp1 paralogs in their genomes (Nlrp1a and Nlrp1c). However, little is known about their expression profile and sequence in different mouse strains. Furthermore, simultaneous expression of these paralogs may lead to competitional binding of Nlrp1b interaction partners needed for inflammasome activation, thus influencing macrophages susceptibility to LT. To more completely understand the role(s) of Nlrp1 paralogs in mice, we surveyed for their expression in a large set of LT-resistant and sensitive mouse macrophages. In addition, we provide sequence comparisons for Nlrp1a and report on previously unrecognized splice variants of Nlrp1b.
Results: Our results show that macrophages from some inbred mouse strains simultaneously express different splice variants of Nlrp1b. In contrast to the highly polymorphic Nlrp1b splice variants, sequencing of expressed Nlrp1a showed the protein to be highly conserved across all mouse strains. We found that Nlrp1a was expressed only in toxin-resistant macrophages, with the sole exception of expression in LT-sensitive CAST/EiJ macrophages.
Conclusions: Our data present a complex picture of Nlrp1 protein variations and provide a basis for elucidating their roles in murine macrophage function. Furthermore, the high conservation of Nlrp1a implies that it might be an important inflammasome sensor in mice.
C1 [Sastalla, Inka; Crown, Devorah; McKenzie, Andrew; Leppla, Stephen H.; Moayeri, Mahtab] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Masters, Seth L.] Walter & Eliza Hall Inst Med Res, Inflammat Div, Parkville, Vic 3052, Australia.
RP Sastalla, I (reprint author), NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, 33 North Dr, Bethesda, MD 20892 USA.
EM sastallai@niaid.nih.gov
OI masters, seth/0000-0003-4763-576X
FU Intramural Research Program of the NIH, National Institute of Allergy
and Infectious Diseases
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Allergy and Infectious Diseases.
NR 32
TC 14
Z9 21
U1 0
U2 2
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 MAR 18
PY 2013
VL 14
AR 188
DI 10.1186/1471-2164-14-188
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 138OH
UT WOS:000318517400001
PM 23506131
ER
PT J
AU Tan, IS
Ramamurthi, KS
AF Tan, Irene S.
Ramamurthi, Kumaran S.
TI Membrane Remodeling: FisB Will Do In a Pinch
SO CURRENT BIOLOGY
LA English
DT Editorial Material
ID BACILLUS-SUBTILIS; FISSION; FUSION; SPORULATION
AB Remodeling of membranes by fission or fusion has been extensively studied in eukaryotes, but proteins directly responsible for mediating such events in bacteria have not been discovered. A recent report identified a protein in Bacillus subtilis that exploits an affinity for a specific lipid to drive membrane fission during sporulation.
C1 [Tan, Irene S.; Ramamurthi, Kumaran S.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Tan, Irene S.] Johns Hopkins Univ, Grad Partnerships Program, NIH, Baltimore, MD 21218 USA.
RP Tan, IS (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM ramamurthiks@mail.nih.gov
RI Ramamurthi, Kumaran/P-3516-2015
NR 13
TC 1
Z9 1
U1 0
U2 9
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 MAR 18
PY 2013
VL 23
IS 6
BP R251
EP R253
DI 10.1016/j.cub.2013.02.002
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 110GG
UT WOS:000316430000018
PM 23518060
ER
PT J
AU Rusmini, M
Griseri, P
Lantieri, F
Matera, I
Hudspeth, KL
Roberto, A
Mikulak, J
Avanzini, S
Rossi, V
Mattioli, G
Jasonni, V
Ravazzolo, R
Pavan, WJ
Pini-Prato, A
Ceccherini, I
Mavilio, D
AF Rusmini, Marta
Griseri, Paola
Lantieri, Francesca
Matera, Ivana
Hudspeth, Kelly L.
Roberto, Alessandra
Mikulak, Joanna
Avanzini, Stefano
Rossi, Valentina
Mattioli, Girolamo
Jasonni, Vincenzo
Ravazzolo, Roberto
Pavan, William J.
Pini-Prato, Alessio
Ceccherini, Isabella
Mavilio, Domenico
TI Induction of RET Dependent and Independent ProInflammatory Programs in
Human Peripheral Blood Mononuclear Cells from Hirschsprung Patients
SO PLOS ONE
LA English
DT Article
ID RECEPTOR TYROSINE KINASE; ENTERIC NERVOUS-SYSTEM; NEURAL CREST;
INCREASED EXPRESSION; HEMATOPOIETIC-CELLS; GDNF GENE; TGF-BETA; DISEASE;
PROTOONCOGENE; MUTATIONS
AB Hirschsprung disease (HSCR) is a rare congenital anomaly characterized by the absence of enteric ganglia in the distal intestinal tract. While classified as a multigenic disorder, the altered function of the RET tyrosine kinase receptor is responsible for the majority of the pathogenesis of HSCR. Recent evidence demonstrate a strong association between RET and the homeostasis of immune system. Here, we utilize a unique cohort of fifty HSCR patients to fully characterize the expression of RET receptor on both innate (monocytes and Natural Killer lymphocytes) and adaptive (B and T lymphocytes) human peripheral blood mononuclear cells (PBMCs) and to explore the role of RET signaling in the immune system. We show that the increased expression of RET receptor on immune cell subsets from HSCR individuals correlates with the presence of loss-of-function RET mutations. Moreover, we demonstrate that the engagement of RET on PBMCs induces the modulation of several inflammatory genes. In particular, RET stimulation with glial-cell line derived neurotrophic factor family (GDNF) and glycosyl-phosphatidylinositol membrane anchored co-receptor alpha 1 (GFR alpha 1) trigger the up-modulation of genes encoding either for chemokines (CCL20, CCL2, CCL3, CCL4, CCL7, CXCL1) and cytokines (IL-1 beta, IL-6 and IL-8) and the down-regulation of chemokine/cytokine receptors (CCR2 and IL8-R alpha). Although at different levels, the modulation of these "RET-dependent genes'' occurs in both healthy donors and HSCR patients. We also describe another set of genes that, independently from RET stimulation, are differently regulated in healthy donors versus HSCR patients. Among these "RET-independent genes'', there are CSF-1R, IL1-R1, IL1-R2 and TGF beta-1, whose levels of transcripts were lower in HSCR patients compared to healthy donors, thus suggesting aberrancies of inflammatory responses at mucosal level. Overall our results demonstrate that immune system actively participates in the physiopathology of HSCR disease by modulating inflammatory programs that are either dependent or independent from RET signaling.
C1 [Rusmini, Marta; Griseri, Paola; Matera, Ivana; Ravazzolo, Roberto; Ceccherini, Isabella] Ist Giannina Gaslini, Genet Mol Lab, IRCCS, I-16148 Genoa, Italy.
[Rusmini, Marta; Lantieri, Francesca; Ravazzolo, Roberto] Univ Genoa, Dept Hlth Sci, Biostat Unit, Genoa, Italy.
[Rusmini, Marta; Hudspeth, Kelly L.; Roberto, Alessandra; Mikulak, Joanna; Ravazzolo, Roberto; Mavilio, Domenico] Humanitas Clin & Res Ctr, Unit Clin & Expt Immunol, Milan, Italy.
[Hudspeth, Kelly L.; Ravazzolo, Roberto; Mavilio, Domenico] Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy.
[Avanzini, Stefano; Rossi, Valentina; Mattioli, Girolamo; Jasonni, Vincenzo; Ravazzolo, Roberto; Pini-Prato, Alessio] Giannina Gaslini Inst, Dept Pediat Surg, IRCCS, Genoa, Italy.
[Ravazzolo, Roberto] Univ Genoa, DINOGMI Dept, Genoa, Italy.
[Pavan, William J.] NHGRI, Mouse Embryol Sect, Genet Dis Res Branch, Bethesda, MD 20892 USA.
RP Mavilio, D (reprint author), Humanitas Clin & Res Ctr, Unit Clin & Expt Immunol, Milan, Italy.
EM domenico.mavilio@humanitas.it
OI Roberto, Alessandra/0000-0001-6615-0026; Mavilio,
Domenico/0000-0001-6147-0952
FU Fondazione Umberto Veronesi; Istituto Superiore di Sanita; Italian
Ministry of Health (Bando Giovani Ricercatori) [GR-2008-1135082];
European Union [204188]
FX MR is a recipient of a fellowship awarded by the Fondazione Umberto
Veronesi. This work is supported by Istituto Superiore di Sanita (E-Rare
grant, 2007 call awarded to IC), by Italian Ministry of Health (Bando
Giovani Ricercatori GR-2008-1135082 awarded to DM) and by European Union
(Marie Curie International Reintegration grant number 204188 awarded to
DM). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 77
TC 7
Z9 8
U1 0
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 MAR 18
PY 2013
VL 8
IS 3
AR e59066
DI 10.1371/journal.pone.0059066
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109ZS
UT WOS:000316411600033
PM 23527089
ER
PT J
AU Yoshimura, T
Howard, OMZ
Ito, T
Kuwabara, M
Matsukawa, A
Chen, KQ
Liu, Y
Liu, MY
Oppenheim, JJ
Wang, JM
AF Yoshimura, Teizo
Howard, O. M. Zack
Ito, Toshihiro
Kuwabara, Masaki
Matsukawa, Akihiro
Chen, Keqiang
Liu, Ying
Liu, Mingyong
Oppenheim, Joost J.
Wang, Ji Ming
TI Monocyte Chemoattractant Protein-1/CCL2 Produced by Stromal Cells
Promotes Lung Metastasis of 4T1 Murine Breast Cancer Cells
SO PLOS ONE
LA English
DT Article
ID TUMOR PROGRESSION; MAMMARY-TUMORS; MACROPHAGE INFILTRATION; INFLAMMATORY
MONOCYTES; SUPPRESSOR-CELLS; IN-VIVO; ANGIOGENESIS; RECRUITMENT;
EXPRESSION; MCP-1
AB MCP-1/CCL2 plays an important role in the initiation and progression of cancer. Since tumor cells produce MCP-1, they are considered to be the main source of this chemokine. Here, we examined whether MCP-1 produced by non-tumor cells affects the growth and lung metastasis of 4T1 breast cancer cells by transplanting them into the mammary pad of WT or MCP-1(-/-) mice. Primary tumors at the injected site grew similarly in both mice; however, lung metastases were markedly reduced in MCP-1(-/-) mice, with significantly longer mouse survival. High levels of MCP-1 mRNA were detected in tumors growing in WT, but not MCP-1(-/-) mice. Serum MCP-1 levels were increased in tumor-bearing WT, but not MCP-1(-/-) mice. Transplantation of MCP-1(-/-) bone marrow cells into WT mice did not alter the incidence of lung metastasis, whereas transplantation of WT bone marrow cells into MCP-1(-/-) mice increased lung metastasis. The primary tumors of MCP-1(-/-) mice consistently developed necrosis earlier than those of WT mice and showed decreased infiltration by macrophages and reduced angiogenesis. Interestingly, 4T1 cells that metastasized to the lung constitutively expressed elevated levels of MCP-1, and intravenous injection of 4T1 cells producing a high level of MCP-1 resulted in increased tumor foci in the lung of WT and MCP-1(-/-) mice. Thus, stromal cell-derived MCP-1 in the primary tumors promotes lung metastasis of 4T1 cells, but tumor cell-derived MCP-1 can also contribute once tumor cells enter the circulation. A greater understanding of the source and role of this chemokine may lead to novel strategies for cancer treatment.
C1 [Yoshimura, Teizo; Howard, O. M. Zack; Chen, Keqiang; Liu, Ying; Liu, Mingyong; Oppenheim, Joost J.; Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Ito, Toshihiro; Kuwabara, Masaki; Matsukawa, Akihiro] Okayama Univ, Dept Pathol & Expt Med, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008530, Japan.
RP Yoshimura, T (reprint author), NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
EM yoshimut@mail.nih.gov
RI Howard, O M Zack/B-6117-2012
OI Howard, O M Zack/0000-0002-0505-7052
FU National Institutes of Health, National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 49
TC 33
Z9 37
U1 0
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 MAR 18
PY 2013
VL 8
IS 3
AR e58791
DI 10.1371/journal.pone.0058791
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109ZS
UT WOS:000316411600011
PM 23527025
ER
PT J
AU Yu, PP
Pisitkun, T
Wang, GH
Wang, R
Katagiri, Y
Gucek, M
Knepper, MA
Geller, HM
AF Yu, Panpan
Pisitkun, Trairak
Wang, Guanghui
Wang, Rong
Katagiri, Yasuhiro
Gucek, Marjan
Knepper, Mark A.
Geller, Herbert M.
TI Global Analysis of Neuronal Phosphoproteome Regulation by Chondroitin
Sulfate Proteoglycans
SO PLOS ONE
LA English
DT Article
ID SPINAL-CORD-INJURY; EXTRACELLULAR-MATRIX; NEURITE OUTGROWTH;
INHIBITORY-ACTIVITY; CANCER-CELLS; AXON GROWTH; GLIAL SCAR;
PHOSPHORYLATION; REGENERATION; GUIDANCE
AB Chondroitin sulfate proteoglycans (CSPGs) are major components of the extracellular matrix which mediate inhibition of axonal regeneration after injury to the central nervous system (CNS). Several neuronal receptors for CSPGs have recently been identified; however, the signaling pathways by which CSPGs restrict axonal growth are still largely unknown. In this study, we applied quantitative phosphoproteomics to investigate the global changes in protein phosphorylation induced by CSPGs in primary neurons. In combination with isobaric Tags for Relative and Absolute Quantitation (iTRAQ) labeling, strong cation exchange chromatography (SCX) fractionation, immobilized metal affinity chromatography (IMAC) and LC-MS/MS, we identified and quantified 2214 unique phosphopeptides corresponding to 1118 phosphoproteins, with 118 changing significantly in abundance with CSPG treatment. The proteins that were regulated by CSPGs included key components of synaptic vesicle trafficking, axon guidance mediated by semaphorins, integrin signaling, cadherin signaling and EGF receptor signaling pathways. A significant number of the regulated proteins are cytoskeletal and related proteins that have been implicated in regulating neurite growth. Another highly represented protein category regulated by CSPGs is nucleic acid binding proteins involved in RNA post-transcriptional regulation. Together, by screening the overall phosphoproteome changes induced by CSPGs, this data expand our understanding of CSPG signaling, which provides new insights into development of strategies for overcoming CSPG inhibition and promoting axonal regeneration after CNS injury.
C1 [Yu, Panpan; Katagiri, Yasuhiro; Geller, Herbert M.] NHLBI, Dev Neurobiol Sect, Cell Biol & Physiol Ctr, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
[Pisitkun, Trairak; Knepper, Mark A.] NHLBI, Epithelial Syst Biol Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Wang, Guanghui; Gucek, Marjan] NHLBI, Prote Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Wang, Rong] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
RP Geller, HM (reprint author), NHLBI, Dev Neurobiol Sect, Cell Biol & Physiol Ctr, Div Intramural Res,NIH, Bldg 10, Bethesda, MD 20892 USA.
EM geller@helix.nih.gov
RI Yu, Panpan/A-4962-2013;
OI Pisitkun, Trairak/0000-0001-6677-2271; Geller,
Herbert/0000-0002-7048-6144
FU National Heart, Lung, and Blood Institute (NHLBI) Intramural Program
FX This research was entirely funded through the National Heart, Lung, and
Blood Institute (NHLBI) Intramural Program. There were no external
funding sources for this study. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 45
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Z9 9
U1 1
U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 18
PY 2013
VL 8
IS 3
AR e59285
DI 10.1371/journal.pone.0059285
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109ZS
UT WOS:000316411600054
PM 23527152
ER
PT J
AU Thompson, J
Pikis, A
Rich, J
Hall, BG
Withers, SG
AF Thompson, John
Pikis, Andreas
Rich, Jamie
Hall, Barry G.
Withers, Stephen G.
TI alpha-Galacturonidase(s): A new class of Family 4 glycoside hydrolases
with strict specificity and a unique CHEV active site motif
SO FEBS LETTERS
LA English
DT Article
DE Glycoside hydrolase Family 4; alpha-Galacturonidase; LplD; CAZy
database; Phylogenetic; pNP-alpha-D-galactopyranosiduronic acid;
Bacillus subtilis
ID PHOSPHO-ALPHA-GLUCOSIDASE; THERMOTOGA-MARITIMA; BACILLUS-SUBTILIS;
ESCHERICHIA-COLI; THERMOPHILIC BACTERIUM; GALACTOSIDASE; HYDROLYSIS;
MECHANISM; 6-PHOSPHO-ALPHA-GLUCOSIDASE; ELIMINATION
AB The catalytic activity of the Family 4 glycosidase LplD protein, whose active site motif is CHEV, is unknown despite its crystal structure having been determined in 2008. Here we identify that activity as being an alpha-galacturonidase whose natural substrate is probably alpha-1,4-di-galacturonate (GalUA(2)). Phylogenetic analysis shows that LplD belongs to a monophyletic clade of CHEV Family 4 enzymes, of which four other members are also shown to be galacturonidases. Family GH 4 enzymes catalyze the cleavage of the glycosidic bond, via a non-canonical redox-assisted mechanism that contrasts with Koshland's double-displacement mechanism. Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies.
C1 [Thompson, John; Pikis, Andreas] NIDCR, Microbial Biochem & Genet Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Pikis, Andreas] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Rich, Jamie; Withers, Stephen G.] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada.
[Hall, Barry G.] Bellingham Res Inst, Bellingham, WA 98229 USA.
RP Thompson, J (reprint author), NIDCR, Microbial Biochem & Genet Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM jthompson@dir.nidcr.nih.gov
FU National Institute of Dental and Craniofacial Research, National
Institutes of Health, Bethesda, MD; Natural Sciences and Engineering
Research Council of Canada
FX We thank Ricardo Dreyfuss for assistance with photography and computer
graphics. This investigation was supported by the Intramural Research
Program (IRP) of the National Institute of Dental and Craniofacial
Research, National Institutes of Health, Bethesda, MD and by the Natural
Sciences and Engineering Research Council of Canada.
NR 33
TC 2
Z9 6
U1 0
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD MAR 18
PY 2013
VL 587
IS 6
BP 799
EP 803
DI 10.1016/j.febslet.2013.02.004
PG 5
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 103VK
UT WOS:000315947400041
PM 23416295
ER
PT J
AU Goldsmith, JC
Wang, WC
AF Goldsmith, Jonathan C.
Wang, Winfred C.
TI Preoperative transfusion in patients with sickle-cell disease
SO LANCET
LA English
DT Editorial Material
ID SURGERY
C1 [Goldsmith, Jonathan C.] NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA.
[Wang, Winfred C.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
RP Goldsmith, JC (reprint author), NHLBI, Div Blood Dis & Resources, Bldg 10, Bethesda, MD 20892 USA.
EM goldsmithjc@nhlbi.nih.gov
NR 9
TC 1
Z9 1
U1 0
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 MAR 16
PY 2013
VL 381
IS 9870
BP 886
EP 888
DI 10.1016/S0140-6736(12)61995-3
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 105LB
UT WOS:000316069700009
PM 23352053
ER
PT J
AU Galbraith, CG
Keller, PJ
Nogales, E
AF Galbraith, Catherine G.
Keller, Philipp J.
Nogales, Eva
TI New technologies in imaging
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Editorial Material
C1 [Galbraith, Catherine G.] NIH, Bethesda, MD 20878 USA.
[Keller, Philipp J.] Howard Hughes Med Inst, Janelia Farm Res Campus, Ashburn, VA 20147 USA.
[Nogales, Eva] Univ Calif Berkeley, Berkeley, CA 94720 USA.
RP Nogales, E (reprint author), Univ Calif Berkeley, Berkeley, CA 94720 USA.
EM enogales@lbl.gov
FU Howard Hughes Medical Institute; NIGMS NIH HHS [P01 GM051487]
NR 0
TC 0
Z9 0
U1 0
U2 4
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 MAR 15
PY 2013
VL 24
IS 6
BP 669
EP 669
DI 10.1091/mbc.E12-12-0867
PG 1
WC Cell Biology
SC Cell Biology
GA 173YV
UT WOS:000321120600001
PM 23486393
ER
PT J
AU Ohara, A
Kasahara, Y
Yamamoto, H
Hata, H
Kobayashi, H
Numachi, Y
Miyoshi, I
Hall, FS
Uhl, GR
Ikeda, K
Sora, I
AF Ohara, Arihisa
Kasahara, Yoshiyuki
Yamamoto, Hideko
Hata, Harumi
Kobayashi, Hideaki
Numachi, Yohtaro
Miyoshi, Ichiro
Hall, F. Scott
Uhl, George R.
Ikeda, Kazutaka
Sora, Ichiro
TI Exclusive expression of VMAT2 in noradrenergic neurons increases
viability of homozygous VMAT2 knockout mice
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Transgenic; Locomotion; Dopamine; Monoamine
ID VESICULAR MONOAMINE TRANSPORTER; DOPAMINE TRANSPORTER; MUTANT MICE;
AMPHETAMINE; GENE; RAT; LOCALIZATION; DISRUPTION; ACTIVATION; LOCOMOTION
AB The vesicular monoamine transporter 2 (VMAT2) translocates monoamine neurotransmitters from the neuronal cytoplasm into synaptic vesicles. Since VMAT2-/- mice die within a few days of birth, it is difficult to analyze the detailed VMAT2 functions using these mice. In this study, we generated human VMAT2 transgenic mice that expressed VMAT2 in noradrenergic neurons with the aim to rescue the lethality of VMAT2 deletion. The expression of human VMAT2 in noradrenergic neurons extended the life of VMAT2-/- mice for up to three weeks, and these mice showed severe growth deficiency compared with VMAT2+/+ mice. These results may indicate that VMAT2 expressed in noradrenergic neurons has crucial roles in survival during the first several weeks after birth, and VMAT2 functions in other monoaminergic systems could be required for further extended survival. Although VMAT2 rescue in noradrenergic neurons did not eliminate the increased morbidity and lethality associated with VMAT2 deletion, the extension of the lifespan in VMAT2 transgenic mice will enable behavioral, pharmacological and pathophysiological studies of VMAT2 function. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Ohara, Arihisa; Kasahara, Yoshiyuki; Hata, Harumi; Kobayashi, Hideaki; Numachi, Yohtaro; Sora, Ichiro] Tohoku Univ, Grad Sch Med, Dept Biol Psychiat, Sendai, Miyagi 9808574, Japan.
[Yamamoto, Hideko; Ikeda, Kazutaka] Tokyo Metropolitan Inst Med Sci, Addict Subst Project, Tokyo 113, Japan.
[Miyoshi, Ichiro] Tohoku Univ, Grad Sch Med, Inst Anim Experimentat, Sendai, Miyagi 9808574, Japan.
[Hall, F. Scott; Uhl, George R.] Natl Inst Drug Abuse, Mol Neurobiol Branch, Intramural Res Program, NIH DHHS, Baltimore, MD USA.
RP Sora, I (reprint author), Tohoku Univ, Grad Sch Med, Dept Biol Psychiat, 1-1 Seiryo Machi, Sendai, Miyagi 9808574, Japan.
EM sora@med.tohoku.ac.jp
RI Ikeda, Kazutaka/I-4694-2013; Kobayashi, Hideaki/C-8617-2009; Hall,
Frank/C-3036-2013
OI Ikeda, Kazutaka/0000-0001-8342-0278; Kobayashi,
Hideaki/0000-0003-3599-0465; Hall, Frank/0000-0002-0822-4063
FU MHLW of Japan; MEXT of Japan; National Institute on Drug Abuse,
NIH/DHHS, USA (GRU); National Institute on Drug Abuse, NIH/DHHS, USA
(FSH)
FX We thank Dr. Kazuto Kobayashi for the kind gift of cDNA for DBH and
Hiromi Suda for technical assistance. This study was supported by a
Grant-in-Aid for Health and Labour Science Research (Research on
Pharmaceutical and Medical Safety) from MHLW of Japan; by Grants-in-Aid
for Core Research for Evolutional Science and Technology (CREST), Global
COE Program (Basic 82 Translational Research Center for Global Brain
Science) from MEXT of Japan and through funding from the Intramural
Research Program of the National Institute on Drug Abuse, NIH/DHHS, USA
(GRU and FSH).
NR 24
TC 4
Z9 5
U1 1
U2 8
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 MAR 15
PY 2013
VL 432
IS 3
BP 526
EP 532
DI 10.1016/j.bbrc.2013.02.014
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 115WS
UT WOS:000316843200023
PM 23410751
ER
PT J
AU Del Valle-Pinero, AY
Van Deventer, HE
Fourie, NH
Martino, AC
Patel, NS
Remaley, AT
Henderson, WA
AF Del Valle-Pinero, Arseima Y.
Van Deventer, Hendrick E.
Fourie, Nicolaas H.
Martino, Angela C.
Patel, Nayan S.
Remaley, Alan T.
Henderson, Wendy A.
TI Gastrointestinal permeability in patients with irritable assessed using
a four probe permeability solution
SO CLINICA CHIMICA ACTA
LA English
DT Article
DE Intestinal permeability; Lactulose-to-mannitol ratio; Sucralose;
Sucrose; Mass spectrometry; Multiple reaction monitoring
ID BOWEL-SYNDROME PATIENTS; INTESTINAL PERMEABILITY; COLONIC PERMEABILITY;
URINE; DISEASE; INFLAMMATION; DECREASES; SUGARS; SERUM; ASSAY
AB Background: Abnormal gastrointestinal permeability has been linked to irritable bowel syndrome (IBS). The lactulose-to-mannitol ratio is traditionally used to assess small intestine permeability while sucralose and sucrose are used to assess colonic and gastric permeability respectively. We used a single 4-probe test solution to assess permeability throughout the gastrointestinal tract in IBS patients and healthy controls by measuring the recovery of the probes in urine after ingestion using a modified liquid chromatography mass spectrometry protocol.
Methods: Fasting participants (N=59) drank a permeability test solution (100 ml: sucralose, sucrose, mannitol, and lactulose). Urine was collected over a 5-h period and kept frozen until analysis. Urinary sugar concentrations were measured using a liquid chromatography/triple quadruple mass spectrometer.
Results: Colonic permeability was significantly lower in IBS patients when compared to healthy controls (p=0.011). Gastric and small intestinal permeability did not significantly differ between the groups.
Conclusions: The study demonstrates the clinical potential of this non-invasive method for assessing alterations in gastrointestinal permeability in patients with IBS. Published by Elsevier B.V.
C1 [Del Valle-Pinero, Arseima Y.; Fourie, Nicolaas H.; Martino, Angela C.; Patel, Nayan S.; Henderson, Wendy A.] NINR, Biobehav Branch, Intramural Res Program, NIH,DHHS, Bethesda, MD 20892 USA.
[Van Deventer, Hendrick E.; Remaley, Alan T.] NIH, Dept Lab Med, DHHS, Bethesda, MD 20892 USA.
[Van Deventer, Hendrick E.; Remaley, Alan T.] NIH, Warren Grant Magnuson Clin Ctr, DHHS, Bethesda, MD 20892 USA.
RP Henderson, WA (reprint author), NINR, Biobehav Unit, NIH, DHHS, Bldg 10,2-1339, Bethesda, MD 20892 USA.
EM hendersw@mail.nih.gov
FU NINR's Intramural Research Training Awards; [1ZIANR000018-03]
FX The authors thank the study participants, NIH Clinical Center and NIDDK
Metabolic Program of Care (Dr. Kong Chen). We also thank Dr. Robert
Shulman for the formulation of the test solution and Dr. Margaret
Heitkemper for her mentorship. This study was funded by NINR's
Intramural Research Training Awards (Del Valle-Pinero, Fourie, and
Patel) and 1ZIANR000018-03 award (PI; Henderson).
NR 31
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U1 1
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0009-8981
J9 CLIN CHIM ACTA
JI Clin. Chim. Acta
PD MAR 15
PY 2013
VL 418
BP 97
EP 101
DI 10.1016/j.cca.2012.12.032
PG 5
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 111OL
UT WOS:000316530500019
PM 23328210
ER
PT J
AU Lilja, AM
Rojdner, J
Mustafiz, T
Thome, CM
Storelli, E
Gonzalez, D
Unger-Lithner, C
Greig, NH
Nordberg, A
Marutle, A
AF Lilja, Anna M.
Rojdner, Jennie
Mustafiz, Tamanna
Thome, Carina M.
Storelli, Elisa
Gonzalez, Daniel
Unger-Lithner, Christina
Greig, Nigel H.
Nordberg, Agneta
Marutle, Amelia
TI Age-Dependent Neuroplasticity Mechanisms in Alzheimer Tg2576 Mice
Following Modulation of Brain Amyloid-beta Levels
SO PLOS ONE
LA English
DT Article
ID NEURAL STEM-CELLS; TRANSGENIC MICE; A-BETA; HIPPOCAMPAL NEUROGENESIS;
ADULT NEUROGENESIS; IMPAIRED NEUROGENESIS; NEUROTROPHIC-FACTOR;
PRECURSOR PROTEIN; DENTATE GYRUS; MOUSE MODEL
AB The objective of this study was to investigate the effects of modulating brain amyloid-beta (A beta) levels at different stages of amyloid pathology on synaptic function, inflammatory cell changes and hippocampal neurogenesis, i.e. processes perturbed in Alzheimer's disease (AD). Young (4- to 6-month-old) and older (15- to 18-month-old) APP(SWE) transgenic (Tg2576) mice were treated with the AD candidate drug (+)-phenserine for 16 consecutive days. We found significant reductions in insoluble A beta 1-42 levels in the cortices of both young and older transgenic mice, while significant reductions in soluble A beta 1-42 levels and insoluble A beta 1-40 levels were only found in animals aged 15-18 months. Autoradiography binding with the amyloid ligand Pittsburgh Compound B (H-3-PIB) revealed a trend for reduced fibrillar A beta deposition in the brains of older phenserine-treated Tg2576 mice. Phenserine treatment increased cortical synaptophysin levels in younger mice, while decreased interleukin-1 beta and increased monocyte chemoattractant protein-1 and tumor necrosis factor-alpha levels were detected in the cortices of older mice. The reduction in A beta 1-42 levels was associated with an increased number of bromodeoxyuridine-positive proliferating cells in the hippocampi of both young and older Tg2576 mice. To determine whether the increased cell proliferation was accompanied by increased neuronal production, the endogenous early neuronal marker doublecortin (DCX) was examined in the dentate gyrus (DG) using immunohistochemical detection. Although no changes in the total number of DCX+-expressing neurons were detected in the DG in Tg2576 mice at either age following (+)-phenserine treatment, dendritic arborization was increased in differentiating neurons in young Tg2576 mice. Collectively, these findings indicate that reducing A beta 1-42 levels in Tg2576 mice at an early pathological stage affects synaptic function by modulating the maturation and plasticity of newborn neurons in the brain. In contrast, lowering A beta levels in Tg2576 mice when Ab plaque pathology is prominent mainly alters the levels of proinflammatory cytokines and chemokines.
C1 [Lilja, Anna M.; Rojdner, Jennie; Mustafiz, Tamanna; Thome, Carina M.; Storelli, Elisa; Gonzalez, Daniel; Unger-Lithner, Christina; Nordberg, Agneta; Marutle, Amelia] Karolinska Inst, Alzheimer Neurobiol Ctr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
[Rojdner, Jennie; Nordberg, Agneta] Karolinska Univ, Huddinge Hosp, Dept Geriatr Med, Stockholm, Sweden.
[Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Marutle, A (reprint author), Karolinska Inst, Alzheimer Neurobiol Ctr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
EM amelia.marutle@ki.se
OI Unger Lithner, Christina/0000-0001-9775-0411
FU Swedish Medical Research Council [05817]; Stockholm County
Council-Karolinska Institutet; Karolinska Institutet Strategic
Neuroscience Program; Swedish Brain Power; Brain Foundation; European
Union; Gun and Bertil Stohne's Foundation; Foundation for Old Servants;
Magnus Bergvall's Foundation; Dementia Association; Lars Hierta Memorial
Foundation; Olle Engkvist Byggmastare Foundation; Karolinska Institutet
Foundations; Johnson & Johnson administered through the Karolinska
Institutet; Alzheimer Association Sweden; Karolinska Institutet for
Funding for new doctoral students at Karolinska Institutet (KID); Erik
and Edith Fernstrom's Foundation; Intramural Research Program, National
Institute on Aging, National Institutes of Health; Torrey pines
Therapeutics; GSK; Wyeth; Novartis; Pfizer; GE Healthcare; Johnson
Johnson
FX This work was supported by grants from the Swedish Medical Research
Council (Project no. 05817), the Stockholm County Council-Karolinska
Institutet (ALF grant), the Karolinska Institutet Strategic Neuroscience
Program, Swedish Brain Power, the Brain Foundation, the INMiND
consortium (Imaging of Neuroinflammation in Neurodegenerative Diseases)
under the Seventh Research Framework Program of the European Union, Gun
and Bertil Stohne's Foundation, the Foundation for Old Servants, Magnus
Bergvall's Foundation, The Dementia Association, The Lars Hierta
Memorial Foundation, the Olle Engkvist Byggmastare Foundation,
Karolinska Institutet Foundations, an academic grant from Johnson &
Johnson administered through the Karolinska Institutet, and the
Alzheimer Association Sweden. AML was supported by a long-term
scholarship from the Karolinska Institutet for Funding for new doctoral
students at Karolinska Institutet (KID), a grant from Erik and Edith
Fernstrom's Foundation, and a stipend from Gun and Bertil Stohne's
Foundation. NHG was supported by the Intramural Research Program,
National Institute on Aging, National Institutes of Health. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.; Agneta Nordberg is PI for
clinical trials sponsored by Torrey pines Therapeutics, GSK, Wyeth, and
has been a consultant for AstraZeneca, served on the advisory board for
Elan, Pfizer, GSK, Novartis, Lundbeck AB, GE Health Care, and received
honorarium for lectures from Novartis, Jansen-Cilag, Pfizer, Merck and
received research grants from Novartis, Pfizer, GE Healthcare, Johnson &
Johnson. The experimental Alzheimer drugs, (2)- phenserine and
(+)phenserine, both derive from Nigel H. Greig's research and are
covered in patents that have been assigned to the National Institutes of
Health and Dr. Greig has no ownership of these patents. None of the
other authors have any conflicts of interest and potential competing
interests. This does not alter the authors' adherence to all the PLOS
ONE policies on sharing data and materials.
NR 65
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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 MAR 15
PY 2013
VL 8
IS 3
AR e58752
DI 10.1371/journal.pone.0058752
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109ZC
UT WOS:000316409800027
PM 23554921
ER
PT J
AU Ou, JX
Bharti, K
Nodari, A
Bertuzzi, S
Arnheiter, H
AF Ou, Jingxing
Bharti, Kapil
Nodari, Alessandro
Bertuzzi, Stefano
Arnheiter, Heinz
TI Vax1/2 Genes Counteract Mitf-Induced Respecification of the Retinal
Pigment Epithelium
SO PLOS ONE
LA English
DT Article
ID TRANSCRIPTION FACTOR MITF; EYE DEVELOPMENT; CELL-DIFFERENTIATION;
ALAGILLE-SYNDROME; OPTIC VESICLE; NEURAL RETINA; HOMEOBOX GENE;
BETA-CATENIN; EXPRESSION; TRANSDIFFERENTIATION
AB During vertebrate eye development, the transcription factor MITF acts to promote the development of the retinal pigment epithelium (RPE). In embryos with Mitf mutations, the future RPE hyperproliferates and is respecified as retinal tissue but only in a small portion of the dorsal RPE. Using a series of genetic crosses, we show that this spatial restriction of RPE respecification is brought about by persistent expression of the anti-retinogenic ventral homeodomain gene Vax2 in the dorso-proximal and both Vax1 and Vax2 in the ventral RPE. We further show that dorso-proximal RPE respecification in Vax2/Mitf double mutants and dorso-proximal and ventral RPE respecification in Vax1/2/Mitf triple mutants result from increased FGF/MAP kinase signaling. In none of the mutants, however, does the distal RPE show signs of hyperproliferation or respecification, likely due to local JAGGED1/NOTCH signaling. Expression studies and optic vesicle culture experiments also suggest a role for NOTCH signaling within the mutant dorsal RPE domains, where ectopic JAGGED1 expression may partially counteract the effects of FGF/ERK1/2 signaling on RPE respecification. The results indicate the presence of complex interplays between distinct transcription factors and signaling molecules during eye development and show how RPE phenotypes associated with mutations in one gene are modulated by expression changes in other genes.
C1 [Ou, Jingxing; Bharti, Kapil; Nodari, Alessandro; Bertuzzi, Stefano; Arnheiter, Heinz] NINDS, Mammalian Dev Sect, NIH, Bethesda, MD 20892 USA.
RP Ou, JX (reprint author), NINDS, Mammalian Dev Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM ouj@nei.nih.gov
OI Bertuzzi, Stefano/0000-0003-4562-3626
FU Intramural Research Program of the National Institutes of Health,
National Institute of Neurological Disorders and Stroke
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Neurological
Disorders and Stroke. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 46
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Z9 4
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 15
PY 2013
VL 8
IS 3
AR e59247
DI 10.1371/journal.pone.0059247
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109ZC
UT WOS:000316409800075
PM 23555005
ER
PT J
AU Rowzee, AM
Perez-Riveros, PJ
Zheng, CY
Krygowski, S
Baum, BJ
Cawley, NX
AF Rowzee, Anne M.
Perez-Riveros, Paola J.
Zheng, Changyu
Krygowski, Sarah
Baum, Bruce J.
Cawley, Niamh X.
TI Expression and Secretion of Human Proinsulin-B10 from Mouse Salivary
Glands: Implications for the Treatment of Type I Diabetes Mellitus
SO PLOS ONE
LA English
DT Article
ID MEDIATED GENE-TRANSFER; INSULIN-RECEPTOR ISOFORM; CARBOXYPEPTIDASE-E;
CELL LINE; MUTANT PROINSULIN; EPITHELIAL-CELLS; SKELETAL-MUSCLE; MICE;
THERAPY; HYPERPROINSULINEMIA
AB Adenovirus (Ad) mediated expression of therapeutic proteins from salivary glands can result in the delivery of biologically active proteins into the circulation where they impart their physiological function. In recent years, Ad vector delivery to salivary glands (SGs) has emerged as a viable option for gene therapy. Here, we engineered a variant of human proinsulin (hProinsulin-B10) into an Ad vector and demonstrated its ability to transduce cell lines, and express a bioactive protein that induces the phosphorylation of AKT, a key insulin signaling molecule. We also examined its expression in mice following delivery of the vector to the parotid gland (PTG), the submandibular gland (SMG) or to the liver via the tail vein and assessed transgenic protein expression and vector containment for each delivery method. In all cases, hProinsulin-B10 was expressed and secreted into the circulation. Lower levels of circulating hProinsulin-B10 were obtained from the PTG while higher levels were obtained from the tail vein and the SMG; however, vector particle containment was best when delivered to the SMG. Expression of hProinsulin-B10 in the SMG of chemically induced diabetic mice prevented excessive hyperglycemia observed in untreated mice. These results demonstrate that hProinsulin-B10 can be expressed and secreted into the circulation from SGs and can function physiologically in vivo. The ability to remediate a diabetic phenotype in a model of type 1 diabetes mellitus is the first step in an effort that may lead to a possible therapy for diabetes.
C1 [Rowzee, Anne M.; Perez-Riveros, Paola J.; Zheng, Changyu; Krygowski, Sarah; Baum, Bruce J.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
[Cawley, Niamh X.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Cawley, NX (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
EM cawleyn@mail.nih.gov
FU Intramural Research Programs of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; National Institute of
Dental and Craniofacial Research, National Institutes of Health
(Bethesda, MD)
FX This work was supported by the Intramural Research Programs of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development and the National Institute of Dental and Craniofacial
Research, National Institutes of Health (Bethesda, MD). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 48
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Z9 6
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 MAR 15
PY 2013
VL 8
IS 3
AR e59222
DI 10.1371/journal.pone.0059222
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109ZC
UT WOS:000316409800072
PM 23554999
ER
PT J
AU Bosire, C
Stampfer, MJ
Subar, AF
Park, Y
Kirkpatrick, SI
Chiuve, SE
Hollenbeck, AR
Reedy, J
AF Bosire, Claire
Stampfer, Meir J.
Subar, Amy F.
Park, Yikyung
Kirkpatrick, Sharon I.
Chiuve, Stephanie E.
Hollenbeck, Albert R.
Reedy, Jill
TI Index-based Dietary Patterns and the Risk of Prostate Cancer in the
NIH-AARP Diet and Health Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE diet; food habits; prostatic neoplasms
ID RETIRED-PERSONS DIET; FATTY-ACIDS; AMERICAN-ASSOCIATION;
NATIONAL-INSTITUTES; EATING INDEX-2005; CHRONIC DISEASE; QUALITY SCORES;
BREAST; WOMEN; FISH
AB Few studies have investigated the relationship between overall diet and the risk of prostate cancer. We examined the association between 3 diet quality indices the Healthy Eating Index-2005 (HEI-2005), Alternate Healthy Eating Index-2010 (AHEI-2010), and alternate Mediterranean diet score (aMED) and prostate cancer risk. At baseline, dietary intake was assessed in a cohort of 293,464 US men in the National Institutes of Health (NIH)-AARP Diet and Health Study. Cox proportional hazards regression was used to estimate hazard ratios. Between 1995 and 2006, we ascertained 23,453 incident cases of prostate cancer, including 2,251 advanced cases and 428 fatal cases. Among men who reported a history of prostate-specific antigen testing, high HEI-2005 and AHEI-2010 scores were associated with lower risk of total prostate cancer (for the highest quintile compared with the lowest, hazard ratio (HR) = 0.92, 95% confidence interval (Cl): 0.86, 0.98, P for trend = 0.01; and HR = 0.93, 95% Cl: 0.88, 0.99, P for trend = 0.05, respectively). No significant association was observed between aMED score and total prostate cancer or between any of the indices and advanced or fatal prostate cancer, regardless of prostate-specific antigen testing status. In individual component analyses, the fish component of aMED and (0-3 fatty acids component of AHEI-2010 were inversely associated with fatal prostate cancer (HR = 0.79, 95% CI: 0.65, 0.96, and HR = 0.94, 95% Cl: 0.90, 0.98, respectively).
C1 [Bosire, Claire; Stampfer, Meir J.; Chiuve, Stephanie E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Stampfer, Meir J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Stampfer, Meir J.; Chiuve, Stephanie E.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Subar, Amy F.; Kirkpatrick, Sharon I.; Reedy, Jill] NCI, Risk Factor Monitoring & Methods Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Chiuve, Stephanie E.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Bosire, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA.
EM cbosire@hsph.harvard.edu
OI Kirkpatrick, Sharon/0000-0001-9896-5975; Park,
Yikyung/0000-0002-6281-489X
FU National Cancer Institute, National Institutes of Health [R25 CA098566]
FX This research was supported in part by the Intermural Research Program
of the National Cancer Institute, National Institutes of Health. C.
Bosire was supported in part by the National Cancer Institute at the
National Institutes of Health (training grant R25 CA098566).
NR 43
TC 29
Z9 30
U1 0
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD MAR 15
PY 2013
VL 177
IS 6
BP 504
EP 513
DI 10.1093/aje/kws261
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 109NE
UT WOS:000316374500004
PM 23408548
ER
PT J
AU McDonald, PG
O'Connell, M
Lutgendorf, SK
AF McDonald, Paige Green
O'Connell, Mary
Lutgendorf, Susan K.
TI Psychoneuroimmunology and cancer: A decade of discovery, paradigm
shifts, and methodological innovations
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Editorial Material
DE Biobehavioral; Psycho-oncology; Tumor biology; Cancer treatment; Cancer
outcomes
ID INDUCED SICKNESS BEHAVIOR; PRIMARY BREAST-CANCER; KILLER-CELL-ACTIVITY;
TUMOR MICROENVIRONMENT; SOCIOECONOMIC-STATUS; OVARIAN-CARCINOMA;
CHILDHOOD-CANCER; BIOBEHAVIORAL FACTORS; HEALTH DISPARITIES; SOCIAL
SUPPORT
AB This article introduces the supplement Advances in Cancer and Brain, Behavior, and Immunity and outlines important discoveries, paradigm shifts, and methodological innovations that have emerged in the past decade to advance mechanistic and translational understanding of biobehavioral influences on tumor biology, cancer treatment-related sequelae, and cancer outcomes. We offer a heuristic framework for research on biobehavioral pathways in cancer. The shifting survivorship landscape is highlighted, and we propose that the changing demographics suggest prudent adoption of a life course perspective of cancer and cancer survivorship. We note opportunities for psychoneuroimmunology (PNI) research to ameliorate the long-term, unintended consequences of aggressive curative intent and call attention to the critical role of reciprocal translational pathways between animal and human studies. Lastly, we briefly summarize the articles included in this compilation and offer our perspectives on future research directions. Published by Elsevier Inc.
C1 [McDonald, Paige Green] NCI, Basic Biobehav & Psychol Sci Branch, BRP, DCCPS,NIH,DHHS, Bethesda, MD 20892 USA.
[O'Connell, Mary] NCI, BRP, DCCPS, NIH,DHHS, Bethesda, MD 20892 USA.
[Lutgendorf, Susan K.] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA.
[Lutgendorf, Susan K.] Univ Iowa, Dept Urol, Iowa City, IA 52242 USA.
[Lutgendorf, Susan K.] Univ Iowa, Dept Obstet & Gynecol, Iowa City, IA 52242 USA.
[Lutgendorf, Susan K.] Univ Iowa, Holden Comprehens Canc Ctr, Iowa City, IA 52242 USA.
RP McDonald, PG (reprint author), 6130 Execut Blvd,MSC 7363, Bethesda, MD 20892 USA.
EM mcdonald.paige@mail.nih.gov
OI Green, Paige/0000-0001-7886-8924
NR 152
TC 10
Z9 10
U1 2
U2 24
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
EI 1090-2139
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD MAR 15
PY 2013
VL 30
SI SI
BP S1
EP S9
DI 10.1016/j.bbi.2013.01.003
PG 9
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 111GW
UT WOS:000316510800001
ER
PT J
AU Camps, J
Pitt, JJ
Emons, G
Hummon, AB
Case, CM
Grade, M
Jones, TL
Nguyen, QT
Ghadimi, BM
Beissbarth, T
Difilippantonio, MJ
Caplen, NJ
Ried, T
AF Camps, Jordi
Pitt, Jason J.
Emons, Georg
Hummon, Amanda B.
Case, Chanelle M.
Grade, Marian
Jones, Tamara L.
Nguyen, Quang T.
Ghadimi, B. Michael
Beissbarth, Tim
Difilippantonio, Michael J.
Caplen, Natasha J.
Ried, Thomas
TI Genetic Amplification of the NOTCH Modulator LNX2 Upregulates the
WNT/beta-Catenin Pathway in Colorectal Cancer
SO CANCER RESEARCH
LA English
DT Article
ID LINEAGE-SURVIVAL ONCOGENE; COPY-NUMBER ALTERATION; TRANSCRIPTIONAL
DEREGULATION; COLON-CANCER; WNT SIGNALS; STEM-CELLS; TUMORS; EXPRESSION;
REVEALS; TUMORIGENESIS
AB Chromosomal copy number alterations (aneuploidy) define the genomic landscape of most cancer cells, but identification of the oncogenic drivers behind these imbalances remains an unfinished task. In this study, we conducted a systematic analysis of colorectal carcinomas that integrated genomic copy number changes and gene expression profiles. This analysis revealed 44 highly overexpressed genes mapping to localized amplicons on chromosome 13, gains of which occur often in colorectal cancers (CRC). RNA interference (RNAi)-mediated silencing identified eight candidates whose loss-of-function reduced cell viability 20% or more in CRC cell lines. The functional space of the genes NUPL1, LNX2, POLR1D, POMP, SLC7A1, DIS3, KLF5, and GPR180 was established by global expression profiling after RNAi exposure. One candidate, LNX2, not previously known as an oncogene, was involved in regulating NOTCH signaling. Silencing LNX2 reduced NOTCH levels but also downregulated the transcription factor TCF7L2 and markedly reduced WNT signaling. LNX2 overexpression and chromosome 13 amplification therefore constitutively activates the WNT pathway, offering evidence of an aberrant NOTCH-WNT axis in CRC. Cancer Res; 73(6); 2003-13. (C)2012 AACR.
C1 [Camps, Jordi; Emons, Georg; Hummon, Amanda B.; Case, Chanelle M.; Grade, Marian; Nguyen, Quang T.; Difilippantonio, Michael J.; Ried, Thomas] NCI, Canc Genom Sect, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20893 USA.
[Pitt, Jason J.; Jones, Tamara L.; Caplen, Natasha J.] NCI, Gene Silencing Sect, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20893 USA.
[Emons, Georg; Grade, Marian; Ghadimi, B. Michael; Beissbarth, Tim] Univ Med Gottingen, Dept Gen & Visceral Surg, Gottingen, Germany.
RP Camps, J (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, 50 South Dr,Bldg 50,Rm 1408, Bethesda, MD 20893 USA.
EM campsj@mail.nih.gov; riedt@mail.nih.gov
RI Caplen, Natasha/H-2768-2016
OI Caplen, Natasha/0000-0002-0001-9460
FU Intramural Research Program of the NIH, National Cancer Institute;
Deutsche Forschungsgemeinschaft [KFO 179]
FX This project was supported by the Intramural Research Program of the
NIH, National Cancer Institute, and through the KFO 179 from the
Deutsche Forschungsgemeinschaft.
NR 49
TC 23
Z9 23
U1 1
U2 19
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 15
PY 2013
VL 73
IS 6
BP 2003
EP 2013
DI 10.1158/0008-5472.CAN-12-3159
PG 11
WC Oncology
SC Oncology
GA 107AR
UT WOS:000316187500035
PM 23319804
ER
PT J
AU Lygate, CA
Aksentijevic, D
Dawson, D
ten Hove, M
Phillips, D
de Bono, JP
Medway, DJ
Sebag-Montefiore, L
Hunyor, I
Channon, KM
Clarke, K
Zervou, S
Watkins, H
Balaban, RS
Neubauer, S
AF Lygate, Craig A.
Aksentijevic, Dunja
Dawson, Dana
ten Hove, Michiel
Phillips, Darci
de Bono, Joseph P.
Medway, Debra J.
Sebag-Montefiore, Liam
Hunyor, Imre
Channon, Keith M.
Clarke, Kieran
Zervou, Sevasti
Watkins, Hugh
Balaban, Robert S.
Neubauer, Stefan
TI Living Without Creatine Unchanged Exercise Capacity and Response to
Chronic Myocardial Infarction in Creatine-Deficient Mice
SO CIRCULATION RESEARCH
LA English
DT Article
DE cardiovascular physiological phenomena; heart contractility; heart
failure; metabolism; mice, transgenic
ID LEFT-VENTRICULAR FUNCTION; ENERGY-METABOLISM; HEART-FAILURE; KNOCKOUT
MICE; MOUSE HEART; RAT-HEART; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE;
BETA-GUANIDINOPROPIONATE; INCREASED SUSCEPTIBILITY; UNCOUPLING PROTEINS
AB Rationale: Creatine is thought to be involved in the spatial and temporal buffering of ATP in energetic organs such as heart and skeletal muscle. Creatine depletion affects force generation during maximal stimulation, while reduced levels of myocardial creatine are a hallmark of the failing heart, leading to the widely held view that creatine is important at high workloads and under conditions of pathological stress.
Objective: We therefore hypothesised that the consequences of creatine-deficiency in mice would be impaired running capacity, and exacerbation of heart failure following myocardial infarction.
Methods and Results: Surprisingly, mice with whole-body creatine deficiency due to knockout of the biosynthetic enzyme (guanidinoacetate N-methyltransferase [GAMT]) voluntarily ran just as fast and as far as controls (>10 km/night) and performed the same level of work when tested to exhaustion on a treadmill. Furthermore, survival following myocardial infarction was not altered, nor was subsequent left ventricular (LV) remodelling and development of chronic heart failure exacerbated, as measured by 3D-echocardiography and invasive hemodynamics. These findings could not be accounted for by compensatory adaptations, with no differences detected between WT and GAMT(-/-) proteomes. Alternative phosphotransfer mechanisms were explored; adenylate kinase activity was unaltered, and although GAMT(-/-) hearts accumulated the creatine precursor guanidinoacetate, this had negligible energy-transfer activity, while mitochondria retained near normal function.
Conclusions: Creatine-deficient mice show unaltered maximal exercise capacity and response to chronic myocardial infarction, and no obvious metabolic adaptations. Our results question the paradigm that creatine is essential for high workload and chronic stress responses in heart and skeletal muscle. (Circ Res. 2013;112:945-955.)
C1 [Lygate, Craig A.; Aksentijevic, Dunja; Dawson, Dana; ten Hove, Michiel; de Bono, Joseph P.; Medway, Debra J.; Sebag-Montefiore, Liam; Hunyor, Imre; Channon, Keith M.; Zervou, Sevasti; Watkins, Hugh; Neubauer, Stefan] Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.
[Lygate, Craig A.; Aksentijevic, Dunja; ten Hove, Michiel; Medway, Debra J.; Sebag-Montefiore, Liam; Hunyor, Imre; Channon, Keith M.; Zervou, Sevasti; Watkins, Hugh; Neubauer, Stefan] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Phillips, Darci; Balaban, Robert S.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
[Clarke, Kieran] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England.
[Lygate, Craig A.; Aksentijevic, Dunja; Medway, Debra J.; Sebag-Montefiore, Liam; Channon, Keith M.; Clarke, Kieran; Zervou, Sevasti; Watkins, Hugh; Neubauer, Stefan] British Heart Fdn Ctr Res Excellence, Oxford, England.
RP Lygate, CA (reprint author), Wellcome Trust Ctr Human Genet, Dept Cardiovasc Med, Roosevelt Dr, Oxford OX3 7BN, England.
EM clygate@well.ox.ac.uk
RI Dawson, Dana/H-3616-2012;
OI Lygate, Craig/0000-0001-6079-0284; Watkins, Hugh/0000-0002-5287-9016
FU British Heart Foundation [RG/10/002/28187]; Wellcome Trust
[090532/Z/09/Z]
FX This work was supported by British Heart Foundation grant
RG/10/002/28187 and Wellcome Trust Core Award, Grant 090532/Z/09/Z.
NR 66
TC 42
Z9 43
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD MAR 15
PY 2013
VL 112
IS 6
BP 945
EP U218
DI 10.1161/CIRCRESAHA.112.300725
PG 32
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 107BO
UT WOS:000316189900011
PM 23325497
ER
PT J
AU Freidlin, B
Korn, EL
AF Freidlin, Boris
Korn, Edward L.
TI Borrowing Information across Subgroups in Phase II Trials: Is It Useful?
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID BAYESIAN CLINICAL-TRIALS; DESIGN; CANCER; SUBTYPES; MODEL; DRUG
AB Because of the heterogeneity of human tumors, cancer patient populations are usually composed of multiple subgroups with different molecular and/or histologic characteristics. In screening new anticancer agents, there might be a scientific rationale to expect some degree of similarity in clinical activity across the subgroups. This poses a challenge to the design of phase II trials assessing clinical activity: Conducting an independent evaluation in each subgroup requires considerable time and resources, whereas a pooled evaluation that completely ignores patient heterogeneity can miss treatments that are only active in some subgroups. It has been suggested that approaches that borrow information across subgroups can improve efficiency in this setting. In particular, the hierarchical Bayesian approach putatively uses the outcome data to decide whether borrowing of information is appropriate. We evaluated potential benefits of the hierarchical Bayesian approach (using models suggested previously) and a simpler pooling approach by simulations. In the phase II setting, the hierarchical Bayesian approach is shown not to work well in the simulations considered, as there appears to be insufficient information in the outcome data to determine whether borrowing across subgroups is appropriate. When there is strong rationale for expecting a uniform level of activity across the subgroups, approaches using simple pooling of information across subgroups may be useful. Clin Cancer Res; 19(6); 1326-34. (C) 2012 AACR.
C1 [Freidlin, Boris; Korn, Edward L.] NCI, Biometr Res Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Freidlin, B (reprint author), NCI, Biometr Res Branch, EPN 8122, Bethesda, MD 20892 USA.
EM freidlinb@ctep.nci.nih.gov
NR 19
TC 4
Z9 4
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2013
VL 19
IS 6
BP 1326
EP 1334
DI 10.1158/1078-0432.CCR-12-1223
PG 9
WC Oncology
SC Oncology
GA 107BE
UT WOS:000316188900004
PM 23303215
ER
PT J
AU Ridnour, LA
Cheng, RYS
Switzer, CH
Heinecke, JL
Ambs, S
Glynn, S
Young, HA
Trinchieri, G
Wink, DA
AF Ridnour, Lisa A.
Cheng, Robert Y. S.
Switzer, Christopher H.
Heinecke, Julie L.
Ambs, Stefan
Glynn, Sharon
Young, Howard A.
Trinchieri, Giorgio
Wink, David A.
TI Molecular Pathways: Toll-like Receptors in the Tumor
Microenvironment-Poor Prognosis or New Therapeutic Opportunity
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID APOPTOSIS-INDUCING LIGAND; NITRIC-OXIDE SYNTHASE; BREAST-CANCER;
UP-REGULATION; METASTATIC MELANOMA; COLORECTAL-CANCER; TOPICAL
IMIQUIMOD; SUPPRESSOR-CELLS; BLADDER-CANCER; LUNG-CANCER
AB Numerous reports have described Toll-like receptor (TLR) expression in the tumor microenvironment as it relates to cancer progression, as well as their involvement in inflammation. While TLRs mediate immune surveillance, clinical studies have associated TLR expression in the tumor with poor patient survival, indicating that TLR expression may affect cancer treatment and survival. This review will examine mechanisms in which TLR activation upregulates protumorigenic pathways, including the induction of inducible nitric oxide synthase (iNOS2) and COX2, which in turn increase TLR expression and promote a feed-forward loop leading to tumor progression and the development of more aggressive tumor phenotypes. These propagating loops involve cancer cell, stroma, and/or immune cell TLR expression. Because of abundant TLR expression in many human tumors, several TLR agonists are now in clinical and preclinical trials and some have shown enhanced efficacy when used as adjuvant with radiation, chemotherapy, or cancer vaccines. These findings suggest that TLR expression influences cancer biology and therapeutic response, which may involve specific interactions within the tumor microenvironment, including mediators of inflammation such as nitric oxide and the arachidonic acid signaling pathways. Clin Cancer Res; 19(6); 1340-6. (C) 2012 AACR.
C1 [Ridnour, Lisa A.; Cheng, Robert Y. S.; Switzer, Christopher H.; Heinecke, Julie L.; Wink, David A.] NCI, Radiat Biol Branch, Bethesda, MD 20892 USA.
[Ambs, Stefan] NCI, Lab Human Carcinogenesis, Bethesda, MD 20892 USA.
[Young, Howard A.; Trinchieri, Giorgio] NCI, Lab Expt Immunol, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21701 USA.
[Glynn, Sharon] Natl Univ Ireland NUI Galway, Prostate Canc Inst, Galway, Ireland.
RP Wink, DA (reprint author), NCI, Radiat Biol Branch, Bldg 10,Room B3-B35, Bethesda, MD 20892 USA.
EM wink@mail.nih.gov
RI Glynn, Sharon/D-7136-2013; Switzer, Christopher/D-9203-2013;
OI Glynn, Sharon/0000-0003-1459-2580; Cheng, Robert/0000-0003-0287-6439
FU Intramural Program, Center for Cancer Research, National Cancer
Institute, NIH
FX This work was funded by the Intramural Program, Center for Cancer
Research, National Cancer Institute, NIH.
NR 66
TC 45
Z9 48
U1 1
U2 22
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 MAR 15
PY 2013
VL 19
IS 6
BP 1340
EP 1346
DI 10.1158/1078-0432.CCR-12-0408
PG 7
WC Oncology
SC Oncology
GA 107BE
UT WOS:000316188900006
PM 23271799
ER
PT J
AU Thomas, A
Mena, E
Kurdziel, K
Venzon, D
Khozin, S
Berman, AW
Choyke, P
Szabo, E
Rajan, A
Giaccone, G
AF Thomas, Anish
Mena, Esther
Kurdziel, Karen
Venzon, David
Khozin, Sean
Berman, Arlene W.
Choyke, Peter
Szabo, Eva
Rajan, Arun
Giaccone, Giuseppe
TI F-18-Fluorodeoxyglucose Positron Emission Tomography in the Management
of Patients with Thymic Epithelial Tumors
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PREOPERATIVE CHEMOTHERAPY; HISTOLOGIC CLASSIFICATION; FDG-PET; THYMOMA;
MALIGNANCIES; CANCER; PREDICTION; MASSES; GRADE
AB Purpose: There are limited data regarding the role of F-18-fluorodeoxyglucose positron emission tomography ([F-18]-FDG PET) imaging in management of patients with thymic epithelial tumors (TET). The primary objective of this study was to assess the usefulness of early [F-18]-FDG PET to monitor treatment efficacy and its correlation with Response Evaluation Criteria in Solid Tumors (RECIST) in patients with TETs.
Experimental Design: [F-18]-FDG PET/computed tomographic (CT) scans were conducted at baseline and after 6 weeks of treatment in patients enrolled in two phase II and one phase I/II clinical trials. On the basis of data from other solid tumors, metabolic response was defined as a reduction of [F-18]-FDG uptake by more than 30% as assessed by average standardized uptake values (SUV) of up to five most metabolically active lesions.
Results: Fifty-six patients with unresectable Masaoka stage III or IV TETs were included. There was a close correlation between early metabolic response and subsequent best response using RECIST (P < 0.0001-0.0003): sensitivity and specificity for prediction of best response were 95% and 100%, respectively. Metabolic responders had significantly longer progression-free survival (median, 11.5 vs. 4.6 months; P = 0.044) and a trend toward longer overall survival (median, 31.8 vs. 18.4 months; P = 0.14) than nonresponders. [F-18]-FDG uptake was significantly higher in thymic carcinoma than in thymoma (P = 0.0004-0.0010).
Conclusion: In patients with advanced TETs, early metabolic response closely correlates with outcome of therapy. [F-18]-FDG PET may be used to monitor treatment efficacy and assess histologic differences in patients with advanced TETs. Clin Cancer Res; 19(6); 1487-93. (C) 2013 AACR.
C1 [Thomas, Anish; Khozin, Sean; Berman, Arlene W.; Rajan, Arun; Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Mena, Esther; Kurdziel, Karen; Choyke, Peter] NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Szabo, Eva] NCI, Div Canc Prevent, Bethesda, MD 20892 USA.
RP Giaccone, G (reprint author), NCI, Room 12N226,10 Ctr Dr, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
RI Giaccone, Giuseppe/E-8297-2017;
OI Giaccone, Giuseppe/0000-0002-5023-7562; Thomas,
Anish/0000-0003-3293-3115
FU National Cancer Institute, NIH
FX The study was supported by Intramural Program, National Cancer
Institute, NIH.
NR 34
TC 6
Z9 6
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2013
VL 19
IS 6
BP 1487
EP 1493
DI 10.1158/1078-0432.CCR-12-2929
PG 7
WC Oncology
SC Oncology
GA 107BE
UT WOS:000316188900020
PM 23382114
ER
PT J
AU Sohl, CD
Kasiviswanathan, R
Copeland, WC
Anderson, KS
AF Sohl, Christal D.
Kasiviswanathan, Rajesh
Copeland, William C.
Anderson, Karen S.
TI Mutations in human DNA polymerase gamma confer unique mechanisms of
catalytic deficiency that mirror the disease severity in mitochondrial
disorder patients
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; REVERSE-TRANSCRIPTASE;
AUTOSOMAL-DOMINANT; POLG1 MUTATIONS; TOXICITY; REPLICATION; DEFECTS;
SUBUNIT; DISCRIMINATION; PARKINSONISM
AB Human mitochondrial DNA polymerase gamma (pol gamma) is solely responsible for the replication and repair of the mitochondrial genome. Unsurprisingly, alterations in pol gamma activity have been associated with mitochondrial diseases such as Alpers syndrome and progressive external ophthalmoplegia. Thus far, predicting the severity of mitochondrial disease based the magnitude of deficiency in pol gamma activity has been difficult. In order to understand the relationship between disease severity in patients and enzymatic defects in vitro, we characterized the molecular mechanisms of four pol gamma mutations, A957P, A957S, R1096C and R1096H, which have been found in patients suffering from aggressive Alpers syndrome to mild progressive external ophthalmoplegia. The A957P mutant showed the most striking deficiencies in the incorporation efficiency of a correct deoxyribonucleotide triphosphate (dNTP) relative to wild-type pol gamma, with less, but still significant incorporation efficiency defects seen in R1096H and R1096C, and only a small decrease in incorporation efficiency observed for A957S. Importantly, this trend matches the disease severity observed in patients very well (approximated as A957P >> R1096C >= R1096H >> A957S, from most severe disease to least severe). Further, the A957P mutation conferred a two orders of magnitude loss of fidelity relative to wild-type pol gamma, indicating that a buildup of mitochondrial genomic mutations may contribute to the death in infancy seen with these patients. We conclude that characterizing the unique molecular mechanisms of pol gamma deficiency for physiologically important mutant enzymes is important for understanding mitochondrial disease and for predicting disease severity.
C1 [Sohl, Christal D.; Anderson, Karen S.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA.
[Kasiviswanathan, Rajesh; Copeland, William C.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Anderson, KS (reprint author), Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St, New Haven, CT 06520 USA.
EM karen.anderson@yale.edu
FU National Institutes of Health [GM049551, GM099289, ES 065080]
FX This work was supported by the National Institutes of Health (GM049551
to K.S.A., GM099289 to C.D.S., ES 065080 to W.C.C.).
NR 46
TC 5
Z9 5
U1 1
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 MAR 15
PY 2013
VL 22
IS 6
BP 1074
EP 1085
DI 10.1093/hmg/dds509
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 108MD
UT WOS:000316296600002
PM 23208208
ER
PT J
AU Iliff, AJ
Renoux, AJ
Krans, A
Usdin, K
Sutton, MA
Todd, PK
AF Iliff, Adam J.
Renoux, Abigail J.
Krans, Amy
Usdin, Karen
Sutton, Michael A.
Todd, Peter K.
TI Impaired activity-dependent FMRP translation and enhanced
mGluR-dependent LTD in Fragile X premutation mice
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID MENTAL-RETARDATION PROTEIN; LONG-TERM DEPRESSION; SPATIAL PROCESSING
DEFICITS; ROBUST PEDIGREE ANALYSIS; GROUP-I MGLUR; MESSENGER-RNA;
TREMOR/ATAXIA SYNDROME; MOUSE MODEL; FULL MUTATION; CGG-REPEAT
AB Fragile X premutation-associated disorders, including Fragile X-associated Tremor Ataxia Syndrome, result from unmethylated CGG repeat expansions in the 5' untranslated region (UTR) of the FMR1 gene. Premutation-sized repeats increase FMR1 transcription but impair rapid translation of the Fragile X mental retardation protein (FMRP), which is absent in Fragile X Syndrome (FXS). Normally, FMRP binds to RNA and regulates metabotropic glutamate receptor (mGluR)-mediated synaptic translation, allowing for dendritic synthesis of several proteins. FMRP itself is also synthesized at synapses in response to mGluR activation. However, the role of activity-dependent translation of FMRP in synaptic plasticity and Fragile X-premutation-associated disorders is unknown. To investigate this question, we utilized a CGG knock-in mouse model of the Fragile X premutation with 120-150 CGG repeats in the mouse Fmr1 5' UTR. These mice exhibit increased Fmr1 mRNA production but impaired FMRP translational efficiency, leading to a modest reduction in basal FMRP expression. Cultured hippocampal neurons and synaptoneurosomes derived from CGG KI mice demonstrate impaired FMRP translation in response to the group I mGluR agonist 3,5-dihydroxyphenylglycine. Electrophysiological analysis reveals enhanced mGluR-mediated long-term depression (mGluR-LTD) at CA3-CA1 synapses in acute hippocampal slices prepared from CGG KI mice relative to wild-type littermates, similar to Fmr1 knockout mice. However, unlike mGluR-LTD in mice completely lacking FMRP, mGluR-LTD in CGG knock-in mice remains dependent on new protein synthesis. These studies demonstrate partially overlapping synaptic plasticity phenotypes in mouse models of FXS and Fragile X premutation disorders and support a role for activity-dependent synthesis of FMRP in enduring forms of synaptic plasticity.
C1 [Iliff, Adam J.] Univ Michigan, Neurosci Grad Program, Ann Arbor, MI 48109 USA.
[Renoux, Abigail J.; Sutton, Michael A.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
[Renoux, Abigail J.; Krans, Amy; Todd, Peter K.] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA.
[Sutton, Michael A.] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA.
[Usdin, Karen] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Sutton, MA (reprint author), Univ Michigan, Mol & Behav Neurosci Inst, Dept Mol & Integrat Physiol, 5067 BSRB,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA.
EM masutton@umich.edu; petertod@med.umich.edu
FU National Institutes of Mental Health [RO1MH085798]; National Institutes
of Neurological Disorders and Stroke [F31NS073372]; National Institutes
of Health [T32GM008322, K08NS069809]; PEW Biomedical Scholars Program;
Harris Professorship
FX This work was supported by the National Institutes of Mental Health
(grant number RO1MH085798 to M.A.S.); the National Institutes of
Neurological Disorders and Stroke (grant number F31NS073372 to A.J.I.);
the National Institutes of Health (grant number T32GM008322 to A.J.R.,
K08NS069809 to P.K.T.); the PEW Biomedical Scholars Program to M.A.S.;
and the Harris Professorship to P.K.T.
NR 91
TC 20
Z9 21
U1 1
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAR 15
PY 2013
VL 22
IS 6
BP 1180
EP 1192
DI 10.1093/hmg/dds525
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 108MD
UT WOS:000316296600010
PM 23250915
ER
PT J
AU Hur, C
Miller, M
Kong, CY
Dowling, EC
Nattinger, KJ
Dunn, M
Feuer, EJ
AF Hur, Chin
Miller, Melecia
Kong, Chung Yin
Dowling, Emily C.
Nattinger, Kevin J.
Dunn, Michelle
Feuer, Eric J.
TI Trends in esophageal adenocarcinoma incidence and mortality
SO CANCER
LA English
DT Article
DE esophageal neoplasms; adenocarcinoma; incidence; mortality;
epidemiology; SEER program
ID BARRETTS-ESOPHAGUS; UNITED-STATES; RISING INCIDENCE; GASTRIC CARDIA;
CANCER; SURVEILLANCE; SURVIVAL; EPIDEMIOLOGY; DIAGNOSIS; RATES
AB BACKGROUND: Over the past several decades, the incidence of esophageal adenocarcinoma (EAC) has rapidly increased. The purpose of this analysis was to examine temporal trends in EAC incidence and mortality within the US population and, in addition, to explore these trends within subgroups of the population. METHODS: The National Cancer Institute (NCI) Surveillance, Epidemiology and End Results (SEER 9) data were used to examine incidence and incidence-based (IB) mortality in EAC from 1975 to 2009. Secular trends in incidence and IB mortality by cancer stage, sex, and race were further characterized using the NCI's Joinpoint Regression program. RESULTS: Based on SEER 9 data, EAC incidence and IB mortality continues to increase in the United States. However, since the mid-1990s, the overall rate of increase in both EAC incidence and IB mortality appears to be slowing. In addition, in early-stage cancers, there is a noticeable leveling off of IB mortality rates and divergence from incidence starting in the late 1990s. Over the study period, the average annual percentage increase in incidence was 6.1% in men and 5.9% in women. CONCLUSIONS: EAC incidence and IB mortality rates continue to rise in the United States, although at a slower rate in more recent years. In early-stage cancers, IB mortality and incidence rates have diverged primarily because IB mortality rates have plateaued beginning in the late 1990s. Although EAC continues to be less common in women, the rate of increase in EAC incidence is similar in both sexes. Cancer 2013. (c) 2012 American Cancer Society.
C1 [Hur, Chin; Miller, Melecia; Kong, Chung Yin; Dowling, Emily C.; Nattinger, Kevin J.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Hur, Chin; Nattinger, Kevin J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Hur, Chin; Kong, Chung Yin] Harvard Univ, Sch Med, Boston, MA USA.
[Dunn, Michelle; Feuer, Eric J.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Hur, C (reprint author), ITA, 101 Merrimac St,10th Floor, Boston, MA 02114 USA.
EM chur@partners.org
OI Hur, Chin/0000-0002-2819-7576
FU National Institutes of Health [R01CA140574, U01CA152926, K25CA133141]
FX This work was supported by the National Institutes of Health (grants
R01CA140574 and U01CA152926 to Dr. Hur and grant K25CA133141 to Dr.
Kong).
NR 22
TC 102
Z9 103
U1 2
U2 23
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 15
PY 2013
VL 119
IS 6
BP 1149
EP 1158
DI 10.1002/cncr.27834
PG 10
WC Oncology
SC Oncology
GA 100JW
UT WOS:000315696600008
PM 23303625
ER
PT J
AU Liu, J
Li, Q
Kuehn, MR
Ying, LTT
Vokes, SA
Chiang, C
AF Liu, Jiang
Li, Qiang
Kuehn, Michael R.
Ying Litingtung
Vokes, Steven A.
Chiang, Chin
TI Sonic hedgehog signaling directly targets Hyaluronic Acid Synthase 2, an
essential regulator of phalangeal joint patterning
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Sonic hedgehog; Limb; Joint patterning; Hyaluronic acid synthase; Gil
factors; Aggrecan
ID CHONDROCYTE PERICELLULAR MATRIX; ARTICULAR-CARTILAGE FORMATION;
HYALURONAN-BINDING PROTEINS; PROMOTES TUMOR PROGRESSION; LIMB BUD
MESENCHYME; VERTEBRATE LIMB; SYNOVIAL JOINT; BREAST-CANCER;
LINK-PROTEIN; CHICK LIMB
AB Sonic hedgehog (Shh) signal, mediated by the Gli family of transcription factors, plays an essential role in the growth and patterning of the limb. Through analysis of the early limb bud transcriptome, we identified a posteriorly-enriched gene, Hyaluronic Acid Synthase 2 (Has2), which encodes a key enzyme for the synthesis of hyaluronan (HA), as a direct target of Gli transcriptional regulation during early mouse limb development. Has2 expression in the limb bud is lost in Shh null and expanded anteriorly in Gli3 mutants. We identified an similar to 3 kb Has2 promoter fragment that contains two strong Gli-binding consensus sequences, and mutation of either site abrogated the ability of Gli1 to activate Has2 promoter in a cell-based assay. Additionally, this promoter fragment is sufficient to direct expression of a reporter gene in the posterior limb mesenchyme. Chromatin immunoprecipitation of DNA-Gli3 protein complexes from limb buds indicated that Gli3 strongly binds to the Has2 promoter region, suggesting that Has2 is a direct transcriptional target of the Shh signaling pathway. We also showed that Has2 conditional mutant (Has2(cko)) hindlimbs display digit-specific patterning defects with longitudinally shifted phalangeal joints and impaired chondrogenesis. Has2(cko) limbs show less capacity for mesenchymal condensation with mislocalized distributions of chondroitin sulfate proteoglycans (CSPGs), aggrecan and link protein. Has2(cko) limb phenotype displays striking resemblance to mutants with defective chondroitin sulfation suggesting tight developmental control of HA on CSPG function. Together, our study identifies Has2 as a novel downstream target of Shh signaling required for joint patterning and chondrogenesis. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Liu, Jiang; Ying Litingtung; Chiang, Chin] Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN 37232 USA.
[Li, Qiang; Vokes, Steven A.] Univ Texas Austin, Inst Cellular & Mol Biol, Austin, TX 78712 USA.
[Kuehn, Michael R.] NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA.
RP Chiang, C (reprint author), Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN 37232 USA.
EM chin.chiang@vanderbilt.edu
RI Kuehn, Michael/A-4573-2014; Xia, Bo/P-9380-2016;
OI Kuehn, Michael/0000-0002-7703-9160; Vokes, Steven/0000-0002-1724-0102
FU [NIHRO1 HD49667]
FX Thanks to all Chiang lab members for suggestions throughout this study.
The hypoxia marker EF5 was made available by the NCI and obtained
through Dr. Cameron Koch at the University of Pennsylvania; we thank
them for this valuable reagent. The Vanderbilt Transgenic
Mouse/Embryonic Stem Cell Shared Resource helped with the injection of
targeted ES cells. This work was funded by NIHRO1 HD49667 to C.C.
NR 102
TC 5
Z9 5
U1 0
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD MAR 15
PY 2013
VL 375
IS 2
BP 160
EP 171
DI 10.1016/j.ydbio.2012.12.018
PG 12
WC Developmental Biology
SC Developmental Biology
GA 102JQ
UT WOS:000315841300006
PM 23313125
ER
PT J
AU Silver, DL
Leeds, KE
Hwang, HW
Miller, EE
Pavan, WJ
AF Silver, Debra L.
Leeds, Karen E.
Hwang, Hun-Way
Miller, Emily E.
Pavan, William J.
TI The EJC component Magoh regulates proliferation and expansion of neural
crest-derived melanocytes
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Melanoblast development; Mitosis; Magoh; Sox10
ID EXON JUNCTION COMPLEX; CELL-DIVISION; MOUSE EMBRYO; SOX10; PATTERNS;
TRANSCRIPTION; PIGMENTATION; EXPRESSION; MIGRATION; PROTEINS
AB Melanoblasts are a population of neural crest-derived cells that generate the pigment-producing cells of our body. Defective melanoblast development and function underlies many disorders including Waardenburg syndrome and melanoma. Understanding the genetic regulation of melanoblast development will help elucidate the etiology of these and other neurocristopathies. Here we demonstrate that Magoh, a component of the exon junction complex, is required for normal melanoblast development. Magoh haploinsufficient mice are hypopigmented and exhibit robust genetic interactions with the transcription factor, Sox10. These phenotypes are caused by a marked reduction in melanoblast number beginning at mid-embryogenesis. Strikingly, while Magoh haploinsufficiency severely reduces epidermal melanoblasts, it does not significantly affect the number of dermal melanoblasts. These data indicate Magoh impacts melanoblast development by disproportionately affecting expansion of epidermal melanoblast populations. We probed the cellular basis for melanoblast reduction and discovered that Magoh mutant melanoblasts do not undergo increased apoptosis, but instead are arrested in mitosis. Mitotic arrest is evident in both Magoh haploinsufficient embryos and in Magoh siRNA treated melanoma cell lines. Together our findings indicate that Magoh-regulated proliferation of melanoblasts in the dermis may be critical for production of epidermally-bound melanoblasts. Our results point to a central role for Magoh in melanocyte development. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Silver, Debra L.; Leeds, Karen E.; Hwang, Hun-Way; Pavan, William J.] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA.
[Silver, Debra L.; Miller, Emily E.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
RP Silver, DL (reprint author), Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
EM debra.silver@duke.edu; bpavan@nhgri.nih.gov
OI Hwang, Hun-Way/0000-0003-0522-1577
FU National Institute for General Medical Sciences PRAT fellowship;
Intramural Research program of NIH/NHGRI; National Institutes of Health
[R00NS064197]
FX The authors thank Laura Baxter for careful reading of the manuscript.
The authors also thank Arturo Incao for mouse husbandry, S. Anderson for
FACs analysis, and Aditi Senthilnathan for analysis of melanocyte
phenotypes. This work was funded in part by a National Institute for
General Medical Sciences PRAT fellowship (to D.L.S.) and by the
Intramural Research program of NIH/NHGRI (to W.J.P.) and by a National
Institutes of Health grant to DLS (R00NS064197).
NR 33
TC 15
Z9 15
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 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD MAR 15
PY 2013
VL 375
IS 2
BP 172
EP 181
DI 10.1016/j.ydbio.2013.01.004
PG 10
WC Developmental Biology
SC Developmental Biology
GA 102JQ
UT WOS:000315841300007
PM 23333945
ER
PT J
AU Yong, KJ
Milenic, DE
Baidoo, KE
Brechbiel, MW
AF Yong, Kwon Joong
Milenic, Diane E.
Baidoo, Kwamena E.
Brechbiel, Martin W.
TI Sensitization of Tumor to Pb-212 Radioimmunotherapy by Gemcitabine
Involves Initial Abrogation of G2 Arrest and Blocked DNA Damage Repair
by Interference With Rad51
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID DISSEMINATED PERITONEAL DISEASE; CELL-CYCLE; TARGETING HER2; CHECKPOINT;
CHK1; RADIATION; APOPTOSIS; MECHANISM; KINASE
AB Purpose: To elucidate the mechanism of the therapeutic efficacy of targeted a-particle radiation therapy using Pb-212-TCMC-trastuzumab together with gemcitabine for treatment of disseminated peritoneal cancers.
Methods and Materials: Mice bearing human colon cancer LS-174T intraperitoneal xenografts were pretreated with gemcitabine, followed by Pb-212-TCMC-trastuzumab and compared with controls.
Results: Treatment with Pb-212-TCMC-trastuzumab increased the apoptotic rate in the S-phase-arrested tumors induced by gemcitabine at earlier time points (6 to 24 hours). Pb-212-TCMC-trastuzumab after gemcitabine pretreatment abrogated G2/M arrest at the same time points, which may be associated with the inhibition of Chk1 phosphorylation and, in turn, cell cycle perturbation, resulting in apoptosis. Pb-212-TCMC-trastuzumab treatment after gemcitabine pretreatment caused depression of DNA synthesis, DNA double-strand breaks, accumulation of unrepaired DNA, and down-regulation of Rad51 protein, indicating that DNA damage repair was blocked. In addition, modification in the chromatin structure of p21 may be associated with transcriptionally repressed chromatin states, indicating that the open structure was delayed at earlier time points.
Conclusion: These findings suggest that the cell-killing efficacy of Pb-212-TCMC-trastuzumab after gemcitabine pretreatment may be associated with abrogation of the G2/M checkpoint, inhibition of DNA damage repair, and chromatin remodeling. (C) 2013 Elsevier Inc.
C1 [Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E.; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, 10 Ctr Dr,MSC 1002,Room B3B69, Bethesda, MD 20892 USA.
EM martinwb@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Cancer Institute, Center for Cancer Research.
NR 20
TC 8
Z9 9
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 15
PY 2013
VL 85
IS 4
BP 1119
EP 1126
DI 10.1016/j.ijrobp.2012.09.015
PG 8
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 101YC
UT WOS:000315809300051
PM 23200172
ER
PT J
AU Strbo, N
Vaccari, M
Pahwa, S
Kolber, MA
Doster, MN
Fisher, E
Gonzalez, L
Stablein, D
Franchini, G
Podack, ER
AF Strbo, Natasa
Vaccari, Monica
Pahwa, Savita
Kolber, Michael A.
Doster, Melvin N.
Fisher, Eva
Gonzalez, Louis
Stablein, Donald
Franchini, Genoveffa
Podack, Eckhard R.
TI Cutting Edge: Novel Vaccination Modality Provides Significant Protection
against Mucosal Infection by Highly Pathogenic Simian Immunodeficiency
Virus
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SHOCK-PROTEIN GP96; RHESUS-MONKEYS; IMMUNE-RESPONSES; DENDRITIC CELLS;
CHALLENGE; RECEPTOR; SIV; EFFICACY; VACCINES
AB Vaccine-induced protection against infection by HIV or highly pathogenic and virulent SIV strains has been limited. In a proof-of-concept study, we show that a novel vaccine approach significantly protects rhesus macaques from mucosal infection by the highly pathogenic strain SIVmac251. We vaccinated three cohorts of 12 macaques each with live, irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp(96)-Ig. Cohort 1 was vaccinated with cells secreting gp96(SIV)Ig carrying SIV peptides. In addition, Cohort 2 received recombinant envelope protein SIV-gp120. Cohort 3 was injected with cells secreting gp(96)-Ig (no SIV Ags) vaccines. Cohort 2 was protected from infection. After seven rectal challenges with highly pathogenic SIVmac251, the hazard ratio was 0.27, corresponding to a highly significant, 73% reduced risk for viral acquisition. The apparent success of the novel vaccine modality recommends further study. The Journal of Immunology, 2013, 190: 2495-2499.
C1 [Strbo, Natasa; Pahwa, Savita; Fisher, Eva; Gonzalez, Louis; Podack, Eckhard R.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA.
[Strbo, Natasa; Pahwa, Savita; Kolber, Michael A.; Gonzalez, Louis; Podack, Eckhard R.] Univ Miami, Miller Sch Med, Ctr AIDS Res, Miami, FL 33136 USA.
[Vaccari, Monica; Doster, Melvin N.; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20817 USA.
[Kolber, Michael A.; Podack, Eckhard R.] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA.
[Stablein, Donald] EMMES Corp, Rockville, MD 20850 USA.
RP Podack, ER (reprint author), Univ Miami, Miller Sch Med, 1600 NW 10th Ave,RMSB 3045, Miami, FL 33136 USA.
EM epodack@miami.edu
FU University of Miami; National Institutes of Health [NIAID R33 AI
073234]; Intramural Research Program of the National Institutes of
Health; National Cancer Institute; Center for Cancer Research; Alliance
for Cancer Gene Therapy, Stamford, CT
FX The work was supported by the National Institutes of Health (Grant NIAID
R33 AI 073234 to E.R.P.), the Intramural Research Program of the
National Institutes of Health (to G.F.), the National Cancer Institute,
the Center for Cancer Research, and the Alliance for Cancer Gene
Therapy, Stamford, CT (to E.R.P.). E.R.P. and the University of Miami
have a financial interest in the commercial development of gp96-Ig-based
vaccines. The other authors have no financial conflicts of interest.
NR 22
TC 19
Z9 19
U1 1
U2 12
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2013
VL 190
IS 6
BP 2495
EP 2499
DI 10.4049/jimmunol.1202655
PG 5
WC Immunology
SC Immunology
GA 099XG
UT WOS:000315657200006
PM 23401588
ER
PT J
AU Sun, XZ
Wiedeman, A
Agrawal, N
Teal, TH
Tanaka, L
Hudkins, KL
Alpers, CE
Bolland, S
Buechler, MB
Hamerman, JA
Ledbetter, JA
Liggitt, D
Elkon, KB
AF Sun, Xizhang
Wiedeman, Alice
Agrawal, Nalini
Teal, Thomas H.
Tanaka, Lena
Hudkins, Kelly L.
Alpers, Charles E.
Bolland, Silvia
Buechler, Matthew B.
Hamerman, Jessica A.
Ledbetter, Jeffrey A.
Liggitt, Denny
Elkon, Keith B.
TI Increased Ribonuclease Expression Reduces Inflammation and Prolongs
Survival in TLR7 Transgenic Mice
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; NECROSIS-FACTOR-ALPHA; T-CELLS;
AUTOANTIBODY SPECIFICITY; IN-VIVO; B-CELLS; ANTIGEN; LIVER; RNA;
AUTOIMMUNITY
AB TLR7 activation is implicated in the pathogenesis of systemic lupus erythematosus. Mice that overexpress TLR7 develop a lupus-like disease with autoantibodies and glomerulonephritis and early death. To determine whether degradation of the TLR7 ligand RNA would alter the course of disease, we created RNase A transgenic (Tg) mice. We then crossed the RNase Tg to TLR7 Tg mice to create TLR7 3 RNase double Tg (DTg) mice. DTg mice had a significantly increased survival associated with reduced activation of T and B lymphocytes and reduced kidney deposition of IgG and C3. We observed massive hepatic inflammation and cell death in TLR7 Tg mice. In contrast, hepatic inflammation and necrosis were strikingly reduced in DTg mice. These findings indicate that high concentrations of serum RNase protect against immune activation and inflammation associated with TLR7 stimulation and that RNase may be a useful therapeutic strategy in the prevention or treatment of inflammation in systemic lupus erythematosus and, possibly, liver diseases. The Journal of Immunology, 2013, 190: 2536-2543.
C1 [Sun, Xizhang; Agrawal, Nalini; Teal, Thomas H.; Tanaka, Lena; Ledbetter, Jeffrey A.; Elkon, Keith B.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Wiedeman, Alice; Buechler, Matthew B.; Hamerman, Jessica A.; Elkon, Keith B.] Univ Washington, Dept Immunol, Seattle, WA 98195 USA.
[Hudkins, Kelly L.; Alpers, Charles E.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Bolland, Silvia] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Buechler, Matthew B.; Hamerman, Jessica A.] Virginia Mason, Benaroya Res Inst, Program Immunol, Seattle, WA 98101 USA.
[Liggitt, Denny] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA.
RP Elkon, KB (reprint author), Univ Washington, Div Rheumatol, 1959 Northeast Pacific St,Box 356428, Seattle, WA 98195 USA.
EM elkon@u.washington.edu
FU Alliance for Lupus Research
FX This work was supported by a grant from the Alliance for Lupus Research
(to K.B.E.).
NR 38
TC 25
Z9 25
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 MAR 15
PY 2013
VL 190
IS 6
BP 2536
EP 2543
DI 10.4049/jimmunol.1202689
PG 8
WC Immunology
SC Immunology
GA 099XG
UT WOS:000315657200011
PM 23382559
ER
PT J
AU Wejksza, K
Lee-Chang, C
Bodogai, M
Bonzo, J
Gonzalez, FJ
Lehrmann, E
Becker, K
Biragyn, A
AF Wejksza, Katarzyna
Lee-Chang, Catalina
Bodogai, Monica
Bonzo, Jessica
Gonzalez, Frank J.
Lehrmann, Elin
Becker, Kevin
Biragyn, Arya
TI Cancer-Produced Metabolites of 5-Lipoxygenase Induce Tumor-Evoked
Regulatory B Cells via Peroxisome Proliferator-Activated Receptor alpha
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID T-CELLS; INFLAMMATORY DISEASES; ACID-METABOLISM; LEUKOTRIENE B-4;
EXPRESSION; INHIBITORS; MICE; METASTASIS; RESPONSES; CYCLOOXYGENASE-2
AB Breast cancer cells facilitate distant metastasis through the induction of immunosuppressive regulatory B cells, designated tBregs. We report in this study that, to do this, breast cancer cells produce metabolites of the 5-lipoxygenase pathway such as leukotriene B-4 to activate the peroxisome proliferator-activated receptor alpha (PPAR alpha) in B cells. Inactivation of leukotriene B-4 signaling or genetic deficiency of PPAR alpha in B cells blocks the generation of tBregs and thereby abrogates lung metastasis in mice with established breast cancer. Thus, in addition to eliciting fatty acid oxidation and metabolic signals, PPAR alpha initiates programs required for differentiation of tBregs. We propose that PPAR alpha in B cells and/or tumor 5-lipoxygenase pathways represents new targets for pharmacological control of tBreg-mediated cancer escape. The Journal of Immunology, 2013, 190: 2575-2584.
C1 [Wejksza, Katarzyna; Lee-Chang, Catalina; Bodogai, Monica; Biragyn, Arya] NIA, Immunoregulat Sect, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA.
[Bonzo, Jessica; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Lehrmann, Elin; Becker, Kevin] NIA, Res Resources Branch, Baltimore, MD 21224 USA.
RP Biragyn, A (reprint author), NIA, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM biragyna@mail.nih.gov
RI Lee-Chang, Catalina/A-5580-2015;
OI Lee-Chang, Catalina/0000-0002-7675-2124; Lehrmann,
Elin/0000-0002-9869-9475
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health.
NR 51
TC 17
Z9 17
U1 0
U2 9
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2013
VL 190
IS 6
BP 2575
EP 2584
DI 10.4049/jimmunol.1201920
PG 10
WC Immunology
SC Immunology
GA 099XG
UT WOS:000315657200015
PM 23408836
ER
PT J
AU Quinn, KM
Da Costa, A
Yamamoto, A
Berry, D
Lindsay, RWB
Darrah, PA
Wang, LS
Cheng, C
Kong, WP
Gall, JGD
Nicosia, A
Folgori, A
Colloca, S
Cortese, R
Gostick, E
Price, DA
Gomez, CE
Esteban, M
Wyatt, LS
Moss, B
Morgan, C
Roederer, M
Bailer, RT
Nabel, GJ
Koup, RA
Seder, RA
AF Quinn, Kylie M.
Da Costa, Andreia
Yamamoto, Ayako
Berry, Dana
Lindsay, Ross W. B.
Darrah, Patricia A.
Wang, Lingshu
Cheng, Cheng
Kong, Wing-Pui
Gall, Jason G. D.
Nicosia, Alfredo
Folgori, Antonella
Colloca, Stefano
Cortese, Riccardo
Gostick, Emma
Price, David A.
Gomez, Carmen E.
Esteban, Mariano
Wyatt, Linda S.
Moss, Bernard
Morgan, Cecilia
Roederer, Mario
Bailer, Robert T.
Nabel, Gary J.
Koup, Richard A.
Seder, Robert A.
TI Comparative Analysis of the Magnitude, Quality, Phenotype, and
Protective Capacity of Simian Immunodeficiency Virus Gag-Specific CD8(+)
T Cells following Human-, Simian-, and Chimpanzee-Derived Recombinant
Adenoviral Vector Immunization
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID REPLICATION-DEFECTIVE ADENOVIRUS; CHRONIC VIRAL-INFECTION; LONG-TERM
IMMUNITY; VACCINE VECTORS; RHESUS-MONKEYS; CELLULAR-IMMUNITY; DENDRITIC
CELLS; IN-VIVO; RESPONSES; IMMUNOGENICITY
AB Recombinant adenoviral vectors (rAds) are the most potent recombinant vaccines for eliciting CD8(+) T cell-mediated immunity in humans; however, prior exposure from natural adenoviral infection can decrease such responses. In this study we show low seroreactivity in humans against simian-(sAd11, sAd16) or chimpanzee-derived (chAd3, chAd63) compared with human-derived (rAd5, rAd28, rAd35) vectors across multiple geographic regions. We then compared the magnitude, quality, phenotype, and protective capacity of CD8(+) T cell responses in mice vaccinated with rAds encoding SIV Gag. Using a dose range (1 x 10(7)-10(9) particle units), we defined a hierarchy among rAd vectors based on the magnitude and protective capacity of CD8(+) T cell responses, from most to least, as: rAd5 and chAd3, rAd28 and sAd11, chAd63, sAd16, and rAd35. Selection of rAd vector or dose could modulate the proportion and/or frequency of IFN-gamma+TNF-alpha+IL-2(+) and KLRG1(+)CD127(-)CD8(+) T cells, but strikingly similar to 30-80% of memory CD8(+) T cells coexpressed CD127 and KLRG1. To further optimize CD8(+) T cell responses, we assessed rAds as part of prime-boost regimens. Mice primed with rAds and boosted with NYVAC generated Gag-specific responses that approached similar to 60% of total CD8(+) T cells at peak. Alternatively, priming with DNA or rAd28 and boosting with rAd5 or chAd3 induced robust and equivalent CD8(+) T cell responses compared with prime or boost alone. Collectively, these data provide the immunologic basis for using specific rAd vectors alone or as part of prime-boost regimens to induce CD8(+) T cells for rapid effector function or robust long-term memory, respectively. The Journal of Immunology, 2013, 190: 2720-2735.
C1 [Quinn, Kylie M.; Da Costa, Andreia; Yamamoto, Ayako; Berry, Dana; Lindsay, Ross W. B.; Darrah, Patricia A.; Wang, Lingshu; Cheng, Cheng; Kong, Wing-Pui; Roederer, Mario; Bailer, Robert T.; Nabel, Gary J.; Koup, Richard A.; Seder, Robert A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Gall, Jason G. D.] GenVec Inc, Gaithersburg, MD 20878 USA.
[Nicosia, Alfredo; Folgori, Antonella; Colloca, Stefano; Cortese, Riccardo] Okairos Srl, I-00144 Rome, Italy.
[Nicosia, Alfredo; Cortese, Riccardo] CEINGE, I-80145 Naples, Italy.
[Nicosia, Alfredo] Univ Naples Federico II, Dept Biochem & Med Biotechnol, I-80131 Naples, Italy.
[Gostick, Emma; Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales.
[Gomez, Carmen E.; Esteban, Mariano] CSIC, Ctr Nacl Biotecnol, E-28049 Madrid, Spain.
[Wyatt, Linda S.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Morgan, Cecilia] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
RP Seder, RA (reprint author), NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr MSC 3025,Bldg 40,Room 3512, Bethesda, MD 20892 USA.
EM rseder@mail.nih.gov
RI Price, David/C-7876-2013; Gomez, Carmen/K-1940-2014
OI Price, David/0000-0001-9416-2737; Gomez, Carmen/0000-0002-5414-7935
FU Foundation for the National Institutes of Health; Collaboration for AIDS
Vaccine Discovery Award rom the Bill and Melinda Gates Foundation
[OPP1039775]
FX This work was supported in part by a grant from the Foundation for the
National Institutes of Health with support from Collaboration for AIDS
Vaccine Discovery Award OPP1039775 from the Bill and Melinda Gates
Foundation.
NR 83
TC 39
Z9 39
U1 2
U2 14
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2013
VL 190
IS 6
BP 2720
EP 2735
DI 10.4049/jimmunol.1202861
PG 16
WC Immunology
SC Immunology
GA 099XG
UT WOS:000315657200030
PM 23390298
ER
PT J
AU Crane, DD
Griffin, AJ
Wehrly, TD
Bosio, CM
AF Crane, Deborah D.
Griffin, Amanda J.
Wehrly, Tara D.
Bosio, Catharine M.
TI B1a Cells Enhance Susceptibility to Infection with Virulent Francisella
tularensis via Modulation of NK/NKT Cell Responses
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID VACCINE STRAIN INFECTION; B-CELLS; TYROSINE KINASE; XID DEFECT;
INTRACELLULAR BACTERIUM; RESPIRATORY-INFECTION; MEDIATED IMMUNITY; HUMAN
NEUTROPHILS; IL-10 PRODUCTION; MICE
AB B1a cells are an important source of natural Abs, Abs directed against T-independent Ags, and are a primary source of IL-10. Bruton's tyrosine kinase (btk) is a cytoplasmic kinase that is essential for mediating signals from the BCR and is critical for development of B1a cells. Consequentially, animals lacking btk have few B1a cells, minimal Ab responses, and can preferentially generate Th1-type immune responses following infection. B1a cells have been shown to aid in protection against infection with attenuated Francisella tularensis, but their role in infection mediated by fully virulent F. tularensis is not known. Therefore, we used mice with defective btk (CBA/CaHN-Btk(XID)/J [XID mice]) to determine the contribution of B1a cells in defense against the virulent F. tularensis ssp. tularensis strain SchuS4. Surprisingly, XID mice displayed increased resistance to pulmonary infection with F. tularensis. Specifically, XID mice had enhanced clearance of bacteria from the lung and spleen and significantly greater survival of infection compared with wild-type controls. We revealed that resistance to infection in XID mice was associated with decreased numbers of IL-10-producing B1a cells and concomitant increased numbers of IL-12-producing macrophages and IFN-gamma-producing NK/NKT cells. Adoptive transfer of wild-type B1a cells into XID mice reversed the control of bacterial replication. Similarly, depletion of NK/NKT cells also increased bacterial burdens in XID mice. Together, our data suggest B cell-NK/NKT cell cross-talk is a critical pivot controlling survival of infection with virulent F. tularensis. The Journal of Immunology, 2013, 190: 2756-2766.
C1 [Crane, Deborah D.; Griffin, Amanda J.; Wehrly, Tara D.; Bosio, Catharine M.] NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Bosio, CM (reprint author), NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
EM bosioc@niaid.nih.gov
RI Bosio, Catharine/D-7456-2015
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 63
TC 15
Z9 15
U1 0
U2 9
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2013
VL 190
IS 6
BP 2756
EP 2766
DI 10.4049/jimmunol.1202697
PG 11
WC Immunology
SC Immunology
GA 099XG
UT WOS:000315657200033
PM 23378429
ER
PT J
AU Canary, LA
Vinton, CL
Morcock, DR
Pierce, JB
Estes, JD
Brenchley, JM
Klatt, NR
AF Canary, Lauren A.
Vinton, Carol L.
Morcock, David R.
Pierce, Jordan B.
Estes, Jacob D.
Brenchley, Jason M.
Klatt, Nichole R.
TI Rate of AIDS Progression Is Associated with Gastrointestinal Dysfunction
in Simian Immunodeficiency Virus-Infected Pigtail Macaques
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CD4(+) T-CELLS; IMMUNE ACTIVATION; HIV-INFECTION; SIV INFECTION;
MICROBIAL TRANSLOCATION; COAGULATION BIOMARKERS; ANTIRETROVIRAL THERAPY;
IL-17 PRODUCTION; SOOTY MANGABEYS; PLASMA-LEVELS
AB During HIV/SIV infection, mucosal immune system dysfunction and systemic immune activation are associated with progression to AIDS; however, it is unclear to what extent pre-existing gastrointestinal damage relates to disease progression postinfection. Pigtail macaques (PTM) are an excellent model in which to assess mucosal dysfunction in relation to HIV/SIV pathogenesis, as the majority of these animals have high levels of gastrointestinal damage, immune activation, and microbial translocation prior to infection, and rapidly progress to AIDS upon SIV infection. In this study, we characterized the mucosal immune environment prior to and throughout SIV infection in 13 uninfected PTM and 9 SIV-infected PTM, of which 3 were slow progressors. This small subset of slow progressors had limited innate immune activation in mucosal tissues in the periphery, which was associated with a more intact colonic epithelial barrier. Furthermore, we found that preinfection levels of microbial translocation, as measured by LP-Sbinding protein, in PTM correlated with the rate of progression to AIDS. These data suggest that pre-existing levels of microbial translocation and gastrointestinal tract dysfunction may influence the rate of HIV disease progression. The Journal of Immunology, 2013, 190: 2959-2965.
C1 [Canary, Lauren A.; Vinton, Carol L.; Pierce, Jordan B.; Brenchley, Jason M.; Klatt, Nichole R.] NIAID, Mol Microbiol Lab, Program Barrier Immun & Repair, NIH, Bethesda, MD 20892 USA.
[Morcock, David R.; Estes, Jacob D.] Frederick Natl Lab Canc Res, Sci Applicat Int Corp Frederick, AIDS & Canc & Virus Program, Frederick, MD 21702 USA.
[Klatt, Nichole R.] Univ Washington, Dept Pharmaceut, Washington Natl Primate Res Ctr, Seattle, WA 98121 USA.
RP Brenchley, JM (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike,Bldg 4,Room 301, Bethesda, MD 20892 USA.
EM jbrenchl@mail.nih.gov; klattnr@uw.edu
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This work was supported in part by Contract HHSN261200800001E from the
National Cancer Institute, National Institutes of Health.
NR 42
TC 22
Z9 22
U1 1
U2 11
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2013
VL 190
IS 6
BP 2959
EP 2965
DI 10.4049/jimmunol.1202319
PG 7
WC Immunology
SC Immunology
GA 099XG
UT WOS:000315657200053
PM 23401593
ER
PT J
AU Carr, GV
Jenkins, KA
Weinberger, DR
Papaleo, F
AF Carr, Gregory V.
Jenkins, Kimberly A.
Weinberger, Daniel R.
Papaleo, Francesco
TI Loss of dysbindin-1 in mice impairs reward-based operant learning by
increasing impulsive and compulsive behavior
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Dysbindin; Impulsivity; Compulsivity; Timing; Schizophrenia; Operant
learning
ID SCHIZOPHRENIA SUSCEPTIBILITY GENE; PREFRONTAL CORTEX; WORKING-MEMORY;
HIPPOCAMPAL-FORMATION; MESSENGER-RNA; 6P22.3 GENE; DOPAMINE; DTNBP1;
BRAIN; OVEREXPRESSION
AB The dystrobrevin-binding protein 1 (DTNBP1)gene, which encodes the dysbindin-1 protein, is a potential schizophrenia susceptibility gene. Polymorphisms in the DTNBP1 gene have been associated with altered cognitive abilities. In the present study, dysbindin-1 null mutant (dys-/-), heterozygous (dys+/-), and wild-type (dys+/+) mice, on a C57BL/6J genetic background, were tested in either a match to sample or nonmatch to sample visual discrimination task. This visual discrimination task was designed to measure rule learning and detect any changes in response timing over the course of testing. Dys-/- mice displayed significant learning deficits and required more trials to acquire this task. However, once criterion was reached, there were no differences between the genotypes on any behavioral measures. Dys-/- mice exhibited increased compulsive and impulsive behaviors compared to control littermates suggesting the inability to suppress incorrectly-timed responses underlies their increased time to acquisition. Indeed, group comparisons of behavior differences between the first and last day of testing showed that only dys-/- mice consistently decreased measures of perseverative, premature, timeout, and total responses. These findings illustrate how some aspects of altered cognitive performance in dys-/- mice might be related to increased impulsive and compulsive behaviors, analogous to cognitive deficits in some individuals with psychiatric disorders: Published by Elsevier B.V.
C1 [Carr, Gregory V.; Jenkins, Kimberly A.; Weinberger, Daniel R.; Papaleo, Francesco] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA.
[Weinberger, Daniel R.] Johns Hopkins Univ, Lieber Inst Brain Dev, Baltimore, MD USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Psychiat Neurol & Neurosci, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, Inst Med Genet, Baltimore, MD 21205 USA.
[Papaleo, Francesco] Ist Italiano Tecnol, Dept Neurosci & Brain Technol, I-16163 Genoa, Italy.
[Papaleo, Francesco] Univ Padua, Dipartimento Sci Farmaco, I-35131 Padua, Italy.
RP Papaleo, F (reprint author), Ist Italiano Tecnol, Dept Neurosci & Brain Technol, Via Morego 30, I-16163 Genoa, Italy.
EM francesco.papaleo@iit.it
RI Carr, Gregory/M-8821-2016;
OI Carr, Gregory/0000-0002-6091-6729; Papaleo,
Francesco/0000-0002-6326-0657
FU National Institute of Mental Health Intramural Research Program; NIMH
Julius Axelrod Memorial Fellowship Training Award; Marie Curie FP7
Reintegration Grant [268247]
FX We thank Qingjun Tian and Jingshan Chen for technical assistance and
Audrey Bebensee, Randy Xun, and Omoye Akhile for critical review of the
manuscript. This research was supported by the National Institute of
Mental Health Intramural Research Program, by the NIMH Julius Axelrod
Memorial Fellowship Training Award, and by the Marie Curie FP7
Reintegration Grant No. 268247. The authors declare that they have no
financial conflicts of interest.
NR 51
TC 6
Z9 6
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD MAR 15
PY 2013
VL 241
BP 173
EP 184
DI 10.1016/j.bbr.2012.12.021
PG 12
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 095BE
UT WOS:000315308700023
PM 23261874
ER
PT J
AU Smith, RM
Papp, AC
Webb, A
Ruble, CL
Munsie, LM
Nisenbaum, LK
Kleinman, JE
Lipska, BK
Sadee, W
AF Smith, Ryan M.
Papp, Audrey C.
Webb, Amy
Ruble, Cara L.
Munsie, Leanne M.
Nisenbaum, Laura K.
Kleinman, Joel E.
Lipska, Barbara K.
Sadee, Wolfgang
TI Multiple Regulatory Variants Modulate Expression of 5-Hydroxytryptamine
2A Receptors in Human Cortex
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE 5-HT2A; depression; HTR2A; mRNA expression; schizophrenia; serotonin
ID MESSENGER-RNA EXPRESSION; 5-HT2A RECEPTOR; T102C POLYMORPHISM;
GENETIC-VARIATION; DIFFERENTIAL EXPRESSION; SEROTONIN TRANSPORTER;
SUICIDAL-BEHAVIOR; PROMOTER ACTIVITY; HUMAN BRAIN; HTR2A GENE
AB Background: The 5-hydroxytryptamine 2A receptor, encoded by HTR2A, is a major postsynaptic target for serotonin in the human brain and a therapeutic drug target. Despite hundreds of genetic associations investigating HTR2A polymorphisms in neuropsychiatric disorders and therapies, the role of genetic HTR2A variability in health and disease remains uncertain.
Methods: To discover and characterize regulatory HTR2A variants, we sequenced whole transcriptomes from 10 human brain regions with massively parallel RNA sequencing and measured allelic expression of multiple HTR2A messenger (m) RNA transcript variants. Following discovery of functional variants, we further characterized their impact on genetic expression in vitro.
Results: Three polymorphisms modulate the use of novel alternative exons and untranslated regions (UTRs), changing expression of RNA and protein. The frequent promoter variant rs6311, widely implicated in human neuropsychiatric disorders, decreases usage of an upstream transcription start site encoding a longer 5'UTR with greater translation efficiency. rs76665058, located in an extended 3'UTR and unique to individuals of African descent, modulates allelic HTR2A mRNA expression. The third single nucleotide polymorphism, unannotated and present in only a single subject, directs alternative splicing of exon 2. Targeted analysis of HTR2A in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study reveals associations between functional variants and depression severity or citalopram response.
Conclusions: Regulatory polymorphisms modulate HTR2A mRNA expression in an isoform-specific manner, directing the usage of novel untranslated regions and alternative exons. These results provide a foundation for delineating the role of HTR2A and serotonin signaling in central nervous system disorders.
C1 [Smith, Ryan M.; Papp, Audrey C.; Sadee, Wolfgang] Ohio State Univ, Coll Med, Dept Pharmacol, Program Pharmacogen, Columbus, OH 43210 USA.
[Webb, Amy] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA.
[Ruble, Cara L.; Munsie, Leanne M.; Nisenbaum, Laura K.] Eli Lilly & Co, Lilly Corp Ctr, Translat Med & Tailored Therapeut, Indianapolis, IN 46285 USA.
[Kleinman, Joel E.; Lipska, Barbara K.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Sadee, Wolfgang] Ohio State Univ, Dept Pharm, Columbus, OH 43210 USA.
[Sadee, Wolfgang] Ohio State Univ, Dept Psychiat, Columbus, OH 43210 USA.
[Sadee, Wolfgang] Ohio State Univ, Dept Human Genet Internal Med, Columbus, OH 43210 USA.
[Sadee, Wolfgang] Ohio State Univ, Dept Environm Hlth Sci, Columbus, OH 43210 USA.
RP Smith, RM (reprint author), 5168 Graves Hall,333 W 10th Ave, Columbus, OH 43210 USA.
EM Ryan.Smith2@osumc.edu
RI Smith, Ryan/H-6898-2012; Lipska, Barbara/E-4569-2017
FU National Institute of General Medical Sciences [U01GM092655]; National
Center for Research Resources [UL1RR025755]; Eli Lilly Collaborative
Research Grant; U.S. Air Force Department of Defense [FA7014-09-2-0004];
National Institute of Mental Health [N01MH90003]
FX This work was supported by the National Institute of General Medical
Sciences (Grant No. U01GM092655 to WS), the National Center for Research
Resources (Grant No. UL1RR025755 to Rebecca D. Jackson), an Eli Lilly
Collaborative Research Grant (to WS), and the U.S. Air Force Department
of Defense (Grant No. FA7014-09-2-0004 to Gail E. Herman).; Data and
biomaterials for the clinical analysis were obtained from the limited
access data sets distributed from the National Institutes of
Health-supported Sequenced Treatment Alternatives to Relieve Depression
(STAR*D) study. STAR*D focused on nonpsychotic major depressive disorder
in adults seen in outpatient settings. The primary purpose of this
research study was to determine which treatments work best if the first
treatment with medication does not produce an acceptable response. The
study was supported by National Institute of Mental Health Contract
Grant No. N01MH90003 to the University of Texas Southwestern Medical
Center.
NR 53
TC 16
Z9 16
U1 1
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAR 15
PY 2013
VL 73
IS 6
BP 546
EP 554
DI 10.1016/j.biopsych.2012.09.028
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 093JA
UT WOS:000315186700010
PM 23158458
ER
PT J
AU Tabb, B
Morcock, DR
Trubey, CM
Quinones, OA
Hao, XP
Smedley, J
Macallister, R
Piatak, M
Harris, LD
Paiardini, M
Silvestri, G
Brenchley, JM
Alvord, WG
Lifson, JD
Estes, JD
AF Tabb, Brian
Morcock, David R.
Trubey, Charles M.
Quinones, Octavio A.
Hao, Xing Pei
Smedley, Jeremy
Macallister, Rhonda
Piatak, Michael, Jr.
Harris, Levelle D.
Paiardini, Mirko
Silvestri, Guido
Brenchley, Jason M.
Alvord, W. Gregory
Lifson, Jeffrey D.
Estes, Jacob D.
TI Reduced Inflammation and Lymphoid Tissue Immunopathology in Rhesus
Macaques Receiving Anti-Tumor Necrosis Factor Treatment During Primary
Simian Immunodeficiency Virus Infection
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE SIV; rhesus macaque; Sooty mangabey; lymph node; inflammation;
adalimumab; TNF; macrophage; fibrosis; collagen; TGFb
ID AFRICAN-GREEN MONKEYS; NF-KAPPA-B; TNF-ALPHA; IMMUNE ACTIVATION; SIV
INFECTION; TYPE-1 INFECTION; RHEUMATOID-ARTHRITIS; HIV-1 INFECTION;
SOOTY MANGABEYS; NATURAL HOSTS
AB Background. Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections induce robust, generalized inflammatory responses that begin during acute infection and lead to pathological systemic immune activation, fibrotic damage of lymphoid tissues, and CD4(+) T-cell loss, pathogenic processes that contribute to disease progression.
Methods. To better understand the contribution of tumor necrosis factor (TNF), a key regulator of acute inflammation, to lentiviral pathogenesis, rhesus macaques newly infected with SIVmac239 were treated for 12 weeks in a pilot study with adalimumab (Humira), a human anti-TNF monoclonal antibody.
Results. Adalimumab did not affect plasma SIV RNA levels or measures of T-cell immune activation (CD38 or Ki67) in peripheral blood or lymph node T cells. However, compared with untreated rhesus macaques, adalimumab-treated rhesus macaques showed attenuated expression of proinflammatory genes, decreased infiltration of polymorphonuclear cells into the T-cell zone of lymphoid tissues, and weaker antiinflammatory regulatory responses to SIV infection (ie, fewer presumed alternatively activated [ ie, CD163(+)] macrophages, interleukin 10-producing cells, and transforming growth factor beta-producing cells), along with reduced lymphoid tissue fibrosis and better preservation of CD4+ T cells.
Conclusions. While HIV/SIV replication drives pathogenesis, these data emphasize the contribution of the inflammatory response to lentiviral infection to overall pathogenesis, and they suggest that early modulation of the inflammatory response may help attenuate disease progression.
C1 [Tabb, Brian; Morcock, David R.; Trubey, Charles M.; Piatak, Michael, Jr.; Lifson, Jeffrey D.; Estes, Jacob D.] SAIC Frederick, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.
[Hao, Xing Pei] SAIC Frederick, Frederick Natl Lab Canc Res, Data Management Serv, Frederick, MD USA.
[Smedley, Jeremy; Macallister, Rhonda] SAIC Frederick, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Quinones, Octavio A.; Alvord, W. Gregory] SAIC Frederick, Frederick Natl Lab Canc Res, Lab Anim Sci Program, Frederick, MD USA.
[Harris, Levelle D.; Brenchley, Jason M.] NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA.
[Paiardini, Mirko; Silvestri, Guido] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
RP Estes, JD (reprint author), Frederick Natl Lab SAIC Frederick, Retroviral Immunopathol Sect ACVP, Ft Detrick Campus,Bldg 535,Rm 411, Frederick, MD 21702 USA.
EM estesj@mail.nih.gov
OI Smedley, Jeremy/0000-0003-3369-4662
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This work was supported by the National Cancer Institute, National
Institutes of Health (contract HHSN261200800001E).
NR 50
TC 26
Z9 30
U1 0
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 MAR 15
PY 2013
VL 207
IS 6
BP 880
EP 892
DI 10.1093/infdis/jis643
PG 13
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 092XO
UT WOS:000315156500003
PM 23087435
ER
PT J
AU Durbin, AP
Kirkpatrick, BD
Pierce, KK
Elwood, D
Larsson, CJ
Lindow, JC
Tibery, C
Sabundayo, BP
Shaffer, D
Talaat, KR
Hynes, NA
Wanionek, K
Carmolli, MP
Luke, CJ
Murphy, BR
Subbarao, K
Whitehead, SS
AF Durbin, Anna P.
Kirkpatrick, Beth D.
Pierce, Kristen K.
Elwood, Daniel
Larsson, Catherine J.
Lindow, Janet C.
Tibery, Cecilia
Sabundayo, Beulah P.
Shaffer, Donna
Talaat, Kawsar R.
Hynes, Noreen A.
Wanionek, Kimberli
Carmolli, Marya P.
Luke, Catherine J.
Murphy, Brian R.
Subbarao, Kanta
Whitehead, Stephen S.
TI A Single Dose of Any of Four Different Live Attenuated Tetravalent
Dengue Vaccines Is Safe and Immunogenic in Flavivirus-naive Adults: A
Randomized, Double-blind Clinical Trial
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE dengue vaccine; live attenuated tetravalent; clinical trial
ID PHASE-I TRIAL; HEMORRHAGIC-FEVER; ANTIBODY-RESPONSES; SHOCK SYNDROME;
CANDIDATE; INFECTION; SEROTYPES; CHILDREN; FORMULATIONS; ADOLESCENTS
AB Background. Dengue virus (DENV) causes hundreds of millions of infections annually. Four dengue sero-types exist, and previous infection with one serotype increases the likelihood of severe disease with a second, heterotypic DENV infection.
Methods. In a randomized, placebo-controlled study, the safety and immunogenicity of 4 different admixtures of a live attenuated tetravalent (LATV) dengue vaccine were evaluated in 113 flavivirus-naive adults. Serum neutralizing antibody levels to all 4 dengue viruses were measured on days 0, 28, 42, and 180.
Results. A single dose of each LATV admixture induced a trivalent or better neutralizing antibody response in 75%-90% of vaccinees. There was no significant difference in the incidence of adverse events between vaccinees and placebo-recipients other than rash. A trivalent or better response correlated with rash and with non-black race (P < .0001). Black race was significantly associated with a reduced incidence of vaccine viremia.
Conclusions. TV003 induced a trivalent or greater antibody response in 90% of flavivirus-naive vaccinees and is a promising candidate for the prevention of dengue. Race was identified as a factor influencing the infectivity of the LATV viruses, reflecting observations of the effect of race on disease severity in natural dengue infection.
C1 [Durbin, Anna P.; Elwood, Daniel; Tibery, Cecilia; Sabundayo, Beulah P.; Shaffer, Donna; Talaat, Kawsar R.; Hynes, Noreen A.; Wanionek, Kimberli] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Kirkpatrick, Beth D.; Pierce, Kristen K.; Larsson, Catherine J.; Lindow, Janet C.; Carmolli, Marya P.] Univ Vermont, Coll Med, Burlington, VT 05405 USA.
[Luke, Catherine J.; Murphy, Brian R.; Subbarao, Kanta; Whitehead, Stephen S.] NIAID, NIH, Bethesda, MD 20892 USA.
[Hynes, Noreen A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Durbin, AP (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, 624 N Broadway,Rm 217, Baltimore, MD 21205 USA.
EM adurbin@jhsph.edu
OI Lindow, Janet/0000-0003-3235-3698
FU National Institute of Allergy and Infectious Diseases (NIAID) Intramural
Research Program, National Institutes of Health [HHSN272200900010C]
FX This work was supported by the National Institute of Allergy and
Infectious Diseases (NIAID) Intramural Research Program, National
Institutes of Health (contract HHSN272200900010C).
NR 40
TC 55
Z9 58
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 MAR 15
PY 2013
VL 207
IS 6
BP 957
EP 965
DI 10.1093/infdis/jis936
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 092XO
UT WOS:000315156500012
PM 23329850
ER
PT J
AU Amornphimoltham, P
Rechache, K
Thompson, J
Masedunskas, A
Leelahavanichkul, K
Patel, V
Molinolo, A
Gutkind, JS
Weigert, R
AF Amornphimoltham, Panomwat
Rechache, Kamil
Thompson, Jamie
Masedunskas, Andrius
Leelahavanichkul, Kantima
Patel, Vyomesh
Molinolo, Alfredo
Gutkind, J. Silvio
Weigert, Roberto
TI Rab25 Regulates Invasion and Metastasis in Head and Neck Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
AB Purpose: Head and neck squamous cell carcinoma (HNSCC) is one of the 10 most common cancers with a 50% five-year survival rate, which has remained unchanged for the past three decades. One of the major reasons for the aggressiveness of this cancer is that HNSCCs readily metastasize to cervical lymph nodes that are abundant in the head and neck region. Hence, discovering new molecules controlling the metastatic process as well as understanding their regulation at the molecular level are essential for effective therapeutic strategies.
Experimental Design: Rab25 expression level was analyzed in HNSCC tissue microarray. We used a combination of intravital microscopy in live animals and immunofluorescence in an in vitro invasion assay to study the role of Rab25 in tumor cell migration and invasion.
Results: In this study, we identified the small GTPase Rab25 as a key regulator of HNSCC metastasis. We observed that Rab25 is downregulated in HNSCC patients. Next, we determined that reexpression of Rab25 in a metastatic cell line is sufficient to block invasion in a three-dimensional collagen matrix and metastasis to cervical lymph nodes in a mouse model for oral cancer. Specifically, Rab25 affects the organization of F-actin at the cell surface, rather than cell proliferation, apoptosis, or tumor angiogenesis.
Conclusion: These findings suggest that Rab25 plays an important role in tumor migration and metastasis, and that understanding its function may lead to the development of new strategies to prevent metastasis in oral cancer patients. (C) 2013 AACR.
C1 [Amornphimoltham, Panomwat; Rechache, Kamil; Thompson, Jamie; Masedunskas, Andrius; Weigert, Roberto] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Intracellular Membrane Trafficking Unit, Bethesda, MD 20892 USA.
[Leelahavanichkul, Kantima; Patel, Vyomesh; Molinolo, Alfredo; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Mol Carcinogenesis Unit, Bethesda, MD 20892 USA.
RP Weigert, R (reprint author), Natl Inst Dent & Craniofacial Res, NIH, 30 Convent Dr, Bethesda, MD 20892 USA.
EM weigertr@mail.nih.gov
OI Masedunskas, Andrius/0000-0002-4533-5467
FU Intramural Research Program of National Institute of Dental and
Craniofacial Research, NIH
FX This research was supported by the Intramural Research Program of
National Institute of Dental and Craniofacial Research, NIH.
NR 50
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U1 1
U2 12
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 MAR 15
PY 2013
VL 19
IS 6
BP 1375
EP 1388
DI 10.1158/1078-0432.CCR-12-2858
PG 14
WC Oncology
SC Oncology
GA V38FY
UT WOS:000209330500001
PM 23340300
ER
PT J
AU Ryan, PB
Madigan, D
Stang, PE
Overhage, JM
Racoosin, JA
Hartzema, AG
AF Ryan, Patrick B.
Madigan, David
Stang, Paul E.
Overhage, J. Marc
Racoosin, Judith A.
Hartzema, Abraham G.
TI Response to Comment on 'Empirical assessment of methods for risk
identification in healthcare data'
SO STATISTICS IN MEDICINE
LA English
DT Article
C1 [Ryan, Patrick B.; Stang, Paul E.] Janssen Res & Dev, Titusville, NJ 08560 USA.
[Ryan, Patrick B.; Madigan, David; Stang, Paul E.; Overhage, J. Marc; Racoosin, Judith A.; Hartzema, Abraham G.] NIH, Observat Med Outcomes Partnership Fdn, Bethesda, MD 20892 USA.
[Ryan, Patrick B.] Univ N Carolina, UNC Eshelman Sch Pharm, Chapel Hill, NC USA.
[Madigan, David] Columbia Univ, Dept Stat, New York, NY USA.
[Overhage, J. Marc] Regenstrief Inst Hlth Care, Indianapolis, IN USA.
[Overhage, J. Marc] Indiana Univ Sch Med, Indianapolis, IN USA.
[Racoosin, Judith A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Hartzema, Abraham G.] Univ Florida, Coll Pharm, Gainesville, FL USA.
RP Ryan, PB (reprint author), Janssen Res & Dev, 1125 Trenton Harbourton Rd,POB 200,MS K304, Titusville, NJ 08560 USA.
EM ryan@omop.org
NR 3
TC 0
Z9 0
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD MAR 15
PY 2013
VL 32
IS 6
BP 1075
EP 1077
DI 10.1002/sim.5725
PG 3
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 092BT
UT WOS:000315094500015
PM 23413215
ER
PT J
AU Mirabello, L
Schiffman, M
Ghosh, A
Rodriguez, AC
Vasiljevic, N
Wentzensen, N
Herrero, R
Hildesheim, A
Wacholder, S
Scibior-Bentkowska, D
Burk, RD
Lorincz, AT
AF Mirabello, Lisa
Schiffman, Mark
Ghosh, Arpita
Rodriguez, Ana C.
Vasiljevic, Natasa
Wentzensen, Nicolas
Herrero, Rolando
Hildesheim, Allan
Wacholder, Sholom
Scibior-Bentkowska, Dorota
Burk, Robert D.
Lorincz, Attila T.
TI Elevated methylation of HPV16 DNA is associated with the development of
high grade cervical intraepithelial neoplasia
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE HPV16; methylation; epidemiology; receiver operating curve; biomarker
ID PAPILLOMAVIRUS TYPE-16 DNA; ATYPICAL SQUAMOUS-CELLS; 16 E6 GENE;
UNDETERMINED SIGNIFICANCE; NATURAL-HISTORY; CPG METHYLATION;
YOUNG-WOMEN; CANCER; INFECTION; CYTOLOGY
AB We explored the association of human papillomavirus type 16 (HPV16) DNA methylation with age, viral load, viral persistence and risk of incident and prevalent high grade CIN (CIN2+) in serially collected specimens from the Guanacaste, Costa Rica cohort. 273 exfoliated cervical cell specimens (diagnostic and pre-diagnostic) were selected: (1) 92 with HPV16 DNA clearance (controls), (2) 72 with HPV16 DNA persistence (without CIN2+) and (3) 109 with CIN2+. DNA was extracted, bisulfite converted and methylation was quantified using pyrosequencing assays at 66 CpGs across the HPV genome. The Kruskal-Wallis test was used to determine significant differences among groups, and receiver operating characteristic curve analyses were used to evaluate how well methylation identified women with CIN2+. In diagnostic specimens, 88% of CpG sites had significantly higher methylation levels in CIN2+ after correction for multiple tests compared with controls. The highest area under the ROC curve (AUC) was 0.82 for CpG site 6457 in L1, and a diagnostic sensitivity of 91% corresponded to a specificity of 60% for CIN2+. Prospectively, 17% of CpG sites had significantly higher methylation in pre-diagnostic CIN2+ specimens (median time of 3 years before diagnosis) versus controls. The strongest pre-diagnostic CpG site was 6367 in L1 with an AUC of 0.76. Age-stratified analyses suggested that women older than the median age of 28 years have an increased risk of precancer associated with high methylation. Higher methylation in CIN2+ cases was not explained by higher viral load. We conclude that elevated levels of HPV16 DNA methylation may be useful to predict concurrently diagnosed as well as future CIN2+.
C1 [Mirabello, Lisa] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Rodriguez, Ana C.; Herrero, Rolando] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica.
[Vasiljevic, Natasa; Scibior-Bentkowska, Dorota; Lorincz, Attila T.] Univ London, Ctr Canc Prevent, Wolfson Inst Prevent Med, London, England.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, Bronx, NY 10467 USA.
RP Mirabello, L (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS-7101, Bethesda, MD 20892 USA.
EM mirabellol@mail.nih.gov; a.lorincz@qmul.ac.uk
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU Intramural Research Program of the NIH, National Cancer Institute,
Division of Cancer Epidemiology and Genetics; Cancer Research UK
[C569/A10404]
FX Grant sponsors: Intramural Research Program of the NIH, National Cancer
Institute, Division of Cancer Epidemiology and Genetics and Cancer
Research UK; Grant number: C569/A10404
NR 28
TC 48
Z9 49
U1 3
U2 30
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAR 15
PY 2013
VL 132
IS 6
BP 1412
EP 1422
DI 10.1002/ijc.27750
PG 11
WC Oncology
SC Oncology
GA 078BG
UT WOS:000314072500019
PM 22847263
ER
PT J
AU Rao, VK
AF Rao, V. Koneti
TI ITP: hematology's Cosette from Les Miserables
SO BLOOD
LA English
DT Editorial Material
ID IMMUNE THROMBOCYTOPENIA; MONOCLONAL-ANTIBODY; RITUXIMAB
C1 NIH, Bethesda, MD 20892 USA.
RP Rao, VK (reprint author), NIH, Bethesda, MD 20892 USA.
FU Intramural NIH HHS
NR 11
TC 2
Z9 2
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 MAR 14
PY 2013
VL 121
IS 11
BP 1928
EP 1930
DI 10.1182/blood-2013-01-477729
PG 5
WC Hematology
SC Hematology
GA 182PR
UT WOS:000321756700004
PM 23493768
ER
PT J
AU Chen, J
Pise-Masison, CA
Shih, JH
Morris, JC
Janik, JE
Conlon, KC
Keating, A
Waldmann, TA
AF Chen, Jing
Pise-Masison, Cynthia A.
Shih, Joanna H.
Morris, John C.
Janik, John E.
Conlon, Kevin C.
Keating, Anne
Waldmann, Thomas A.
TI Markedly additive antitumor activity with the combination of a selective
survivin suppressant YM155 and alemtuzumab in adult T-cell leukemia
SO BLOOD
LA English
DT Article
ID MONOCLONAL-ANTIBODY; MURINE MODEL; PHASE-II; EFFECTIVE THERAPY; COMPLETE
RESPONSE; INTERFERON-ALPHA; CANCER CELLS; LYMPHOMA; EXPRESSION;
LEUKEMIA/LYMPHOMA
AB Adult T-cell leukemia (ATL) is an aggressive malignancy of CD4(+)CD25(+) lymphocytes caused by human T-cell lymphotropic virus type 1. Currently, there is no accepted curative therapy for ATL. In gene expression profiling, the antiapoptotic protein survivin (BIRC5) demonstrated a striking increase in ATL, and its expression was increased in patient ATL cells resistant to the anti-CD52 monoclonal antibody alemtuzumab (Campath-1H). In this study, we investigated the antitumor activity of a small-molecule survivin suppressant YM155 alone and in combination with alemtuzumab in a murine model of human ATL (MET-1). Both YM155 alone and its combination with alemtuzumab demonstrated therapeutic efficacy by lowering serum soluble IL-2R alpha (sIL-2R alpha) levels (P < .001) and prolonged the survival of tumor-bearing mice (P < .0001). Moreover, the combination of YM155 with alemtuzumab demonstrated markedly additive antitumor activity by significantly lowering serum sIL-2R alpha levels and improving the survival of leukemia-bearing mice compared with monotherapy with either YM155 (P < .001) or alemtuzumab (P < .05). More significantly, all mice that received the combination therapy survived and were tumor free >6 months after treatment. Our data support a clinical trial of the combination of YM155 with alemtuzumab in ATL. #NCT00061048.
C1 [Chen, Jing; Morris, John C.; Janik, John E.; Conlon, Kevin C.; Waldmann, Thomas A.] NCI, Metab Branch, Bethesda, MD 20892 USA.
[Pise-Masison, Cynthia A.] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Shih, Joanna H.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Keating, Anne] Astellas Pharma US Inc, Deerfield, IL USA.
RP Waldmann, TA (reprint author), NIH, Bldg 10,Room 4N115,10 Ctr Dr, Bethesda, MD 20892 USA.
EM tawald@helix.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This work was supported by the intramural research program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 49
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Z9 25
U1 0
U2 5
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 MAR 14
PY 2013
VL 121
IS 11
BP 2029
EP 2037
DI 10.1182/blood-2012-05-427773
PG 9
WC Hematology
SC Hematology
GA 182PR
UT WOS:000321756700020
PM 23321252
ER
PT J
AU Adams, MA
Ding, D
Sallis, JF
Bowles, HR
Ainsworth, BE
Bergman, P
Bull, FC
Carr, H
Craig, CL
De Bourdeaudhuij, I
Gomez, LF
Hagstromer, M
Klasson-Heggebo, L
Inoue, S
Lefevre, J
Macfarlane, DJ
Matsudo, S
Matsudo, V
McLean, G
Murase, N
Sjostrom, M
Tomten, H
Volbekiene, V
Bauman, A
AF Adams, Marc A.
Ding, Ding
Sallis, James F.
Bowles, Heather R.
Ainsworth, Barbara E.
Bergman, Patrick
Bull, Fiona C.
Carr, Harriette
Craig, Cora L.
De Bourdeaudhuij, Ilse
Fernando Gomez, Luis
Hagstromer, Maria
Klasson-Heggebo, Lena
Inoue, Shigeru
Lefevre, Johan
Macfarlane, Duncan J.
Matsudo, Sandra
Matsudo, Victor
McLean, Grant
Murase, Norio
Sjostrom, Michael
Tomten, Heidi
Volbekiene, Vida
Bauman, Adrian
TI Patterns of neighborhood environment attributes related to physical
activity across 11 countries: a latent class analysis
SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY
LA English
DT Article
DE Built environment; International; Recreation; Surveillance; Exercise
ID BUILT ENVIRONMENT; WALKABILITY SCALE; OBESITY; WALKING; RECREATION;
ADULTS; DETERMINANTS; RELIABILITY; VALIDITY; TRANSIT
AB Background: Neighborhood environment studies of physical activity (PA) have been mainly single-country focused. The International Prevalence Study (IPS) presented a rare opportunity to examine neighborhood features across countries. The purpose of this analysis was to: 1) detect international neighborhood typologies based on participants' response patterns to an environment survey and 2) to estimate associations between neighborhood environment patterns and PA.
Methods: A Latent Class Analysis (LCA) was conducted on pooled IPS adults (N=11,541) aged 18 to 64 years old (mean=37.5 +/- 12.8 yrs; 55.6% women) from 11 countries including Belgium, Brazil, Canada, Colombia, Hong Kong, Japan, Lithuania, New Zealand, Norway, Sweden, and the U. S. This subset used the Physical Activity Neighborhood Environment Survey (PANES) that briefly assessed 7 attributes within 10-15 minutes walk of participants' residences, including residential density, access to shops/services, recreational facilities, public transit facilities, presence of sidewalks and bike paths, and personal safety. LCA derived meaningful subgroups from participants' response patterns to PANES items, and participants were assigned to neighborhood types. The validated short-form International Physical Activity Questionnaire (IPAQ) measured likelihood of meeting the 150 minutes/week PA guideline. To validate derived classes, meeting the guideline either by walking or total PA was regressed on neighborhood types using a weighted generalized linear regression model, adjusting for gender, age and country.
Results: A 5-subgroup solution fitted the dataset and was interpretable. Neighborhood types were labeled, "Overall Activity Supportive (52% of sample)", "High Walkable and Unsafe with Few Recreation Facilities (16%)", "Safe with Active Transport Facilities (12%)", "Transit and Shops Dense with Few Amenities (15%)", and "Safe but Activity Unsupportive (5%)". Country representation differed by type (e. g., U. S. disproportionally represented "Safe but Activity Unsupportive"). Compared to the Safe but Activity Unsupportive, two types showed greater odds of meeting PA guideline for walking outcome (High Walkable and Unsafe with Few Recreation Facilities, OR=2.26 (95% CI 1.18-4.31); Overall Activity Supportive, OR=1.90 (95% CI 1.13-3.21). Significant but smaller odds ratios were also found for total PA.
Conclusions: Meaningful neighborhood patterns generalized across countries and explained practical differences in PA. These observational results support WHO/UN recommendations for programs and policies targeted to improve features of the neighborhood environment for PA.
C1 [Adams, Marc A.; Ainsworth, Barbara E.] Arizona State Univ, Sch Nutr & Hlth Promot, Phoenix, AZ USA.
[Sallis, James F.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Bowles, Heather R.] NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, NIH, Bethesda, MD 20892 USA.
[Hagstromer, Maria; Sjostrom, Michael] Karolinska Inst, Unit Prevent Nutr, Dept Biosci & Nutr, Stockholm, Sweden.
[Bergman, Patrick] Linnaeus Univ, Sch Educ Psychol & Sports Sci, Kalmar, Sweden.
[Bull, Fiona C.] Univ Western Australia, Sch Populat Hlth, Crawley, WA, Australia.
[Craig, Cora L.] Canadian Fitness & Lifestyle Res Inst, Sch Publ Hlth, Ottawa, ON, Canada.
[Klasson-Heggebo, Lena] Valnesfjord Rehabil Ctr, Valnesfjord, Norway.
[Carr, Harriette; McLean, Grant] Sport New Zealand, Minist Hlth, Wellington, New Zealand.
[De Bourdeaudhuij, Ilse] Univ Ghent, Dept Movement & Sport Sci, B-9000 Ghent, Belgium.
[Fernando Gomez, Luis] Pontificia Univ Javeriana, Bogota, Colombia.
[Inoue, Shigeru; Murase, Norio] Tokyo Med Univ, Dept Prevent Med & Publ Hlth, Tokyo 1608402, Japan.
[Lefevre, Johan] Katholic Univ, Dept Kinesiol, Leuven, Belgium.
[Macfarlane, Duncan J.] Univ Hong Kong, Inst Human Performance, Hong Kong, Hong Kong, Peoples R China.
[Matsudo, Sandra; Matsudo, Victor] CELAFISCS, Ctr Studies, Phys Fitness Res Ctr Sao Caetano do Sul, Sao Paulo, Brazil.
[Tomten, Heidi] Oppegard Municipal, Oppegard Cty, Norway.
[Volbekiene, Vida] Lithuanian Acad Phys Educ, Dept Sport Sci, Kaunas, Lithuania.
[Ding, Ding; Bauman, Adrian] Univ Sydney, Prevent Res Collaborat, Sydney, NSW 2006, Australia.
RP Adams, MA (reprint author), Arizona State Univ, Sch Nutr & Hlth Promot, Phoenix, AZ USA.
EM marc.adams@asu.edu
RI Bull, Fiona/G-4148-2012; Bergman, Patrick/B-5906-2012; Adams,
Marc/C-3513-2013; Matsudo, Sandra/E-7309-2013; Matsudo,
Victor/E-8122-2013
OI Bergman, Patrick/0000-0003-4934-8684; Adams, Marc/0000-0001-6310-1472;
Matsudo, Sandra/0000-0002-3705-9458; Hagstromer,
Maria/0000-0002-4607-8677; Matsudo, Victor/0000-0003-3552-486X
FU National Heart, Lung and Blood Institute [T32HL079891]; American Heart
Association [12BGIA9280017]
FX This manuscript was supported in part by grants from National Heart,
Lung and Blood Institute (T32HL079891) and the American Heart
Association (12BGIA9280017).
NR 49
TC 19
Z9 19
U1 6
U2 73
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 MAR 14
PY 2013
VL 10
AR 34
DI 10.1186/1479-5868-10-34
PG 11
WC Nutrition & Dietetics; Physiology
SC Nutrition & Dietetics; Physiology
GA 118OK
UT WOS:000317034600001
PM 23497187
ER
PT J
AU Prustel, T
Meier-Schellersheim, M
AF Pruestel, Thorsten
Meier-Schellersheim, Martin
TI Theory of reversible diffusion-influenced reactions with non-Markovian
dissociation in two space dimensions
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID PROTON-TRANSFER REACTIONS; GEMINATE RECOMBINATION; DYNAMICS
AB We investigate the reversible diffusion-influenced reaction of an isolated pair in the presence of a non-Markovian generalization of the backreaction boundary condition in two space dimensions. Following earlier work by Agmon and Weiss, we consider residence time probability densities that decay slower than an exponential and that are characterized by a single parameter 0 < sigma <= 1. We calculate an exact expression for a Green's function of the two-dimensional diffusion equation subject to a non-Markovian backreaction boundary condition that is valid for arbitrary sigma and for all times. We use the obtained expression to derive the survival probability for the initially unbound pair and we calculate an exact expression for the probability S(t vertical bar*) that the initially bound particle is unbound. Finally, we obtain an approximate solution for long times. In particular, we show that the ultimate fate of the bound state is complete dissociation, as in the Markovian case. However, the limiting value is approached quite differently: Instead of a similar to t(-1) decay, we obtain 1 - S(t vertical bar*) similar to t(-sigma) ln t. The derived expressions should be relevant for a better understanding of reversible membrane-bound reactions in cell biology. [http://dx.doi.org/10.1063/1.4794311]
C1 [Pruestel, Thorsten; Meier-Schellersheim, Martin] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
RP Prustel, T (reprint author), NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
EM prustelt@niaid.nih.gov; mms@niaid.nih.gov
FU NIH, National Institute of Allergy and Infectious Diseases
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Allergy and Infectious Diseases. We would
like to thank Bastian R. Angermann and Frederick Klauschen for helpful
discussions.
NR 24
TC 3
Z9 3
U1 0
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 MAR 14
PY 2013
VL 138
IS 10
AR 104112
DI 10.1063/1.4794311
PG 8
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 111TK
UT WOS:000316543400013
PM 23514470
ER
PT J
AU Shah, MA
Wainberg, ZA
Catenacci, DVT
Hochster, HS
Ford, J
Kunz, P
Lee, FC
Kallender, H
Cecchi, F
Rabe, DC
Keer, H
Martin, AM
Liu, Y
Gagnon, R
Bonate, P
Liu, L
Gilmer, T
Bottaro, DP
AF Shah, Manish A.
Wainberg, Zev A.
Catenacci, Daniel V. T.
Hochster, Howard S.
Ford, James
Kunz, Pamela
Lee, Fa-Chyi
Kallender, Howard
Cecchi, Fabiola
Rabe, Daniel C.
Keer, Harold
Martin, Anne-Marie
Liu, Yuan
Gagnon, Robert
Bonate, Peter
Liu, Li
Gilmer, Tona
Bottaro, Donald P.
TI Phase II Study Evaluating 2 Dosing Schedules of Oral Foretinib
(GSK1363089), cMET/VEGFR2 Inhibitor, in Patients with Metastatic Gastric
Cancer
SO PLOS ONE
LA English
DT Article
ID VASCULAR ENDOTHELIAL GROWTH; C-MET; ACQUIRED-RESISTANCE; THERAPEUTIC
TARGET; CLINICAL-FEATURES; PROGNOSTIC MARKER; AMPLIFICATION; CARCINOMA;
GENE; ADENOCARCINOMA
AB Purpose: The receptors for hepatocyte and vascular endothelial cell growth factors (MET and VEGFR2, respectively) are critical oncogenic mediators in gastric adenocarcinoma. The purpose is to examine the safety and efficacy of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2, and VEGFR2 receptors, for the treatment of metastatic gastric adenocarcinoma.
Patients and Methods: Foretinib safety and tolerability, and objective response rate (ORR) were evaluated in patients using intermittent (240 mg/day, for 5 days every 2 weeks) or daily (80 mg/day) dosing schedules. Thirty evaluable patients were required to achieve alpha = 0.10 and beta = 0.2 to test the alternative hypothesis that single-agent foretinib would result in an ORR of >= 25%. Up to 10 additional patients could be enrolled to ensure at least eight with MET amplification. Correlative studies included tumor MET amplification, MET signaling, pharmacokinetics and plasma biomarkers of foretinib activity.
Results: From March 2007 until October 2009, 74 patients were enrolled; 74% male; median age, 61 years (range, 25-88); 93% had received prior therapy. Best response was stable disease (SD) in 10 (23%) patients receiving intermittent dosing and five (20%) receiving daily dosing; SD duration was 1.9-7.2 months (median 3.2 months). Of 67 patients with tumor samples, 3 had MET amplification, one of whom had SD. Treatment-related adverse events occurred in 91% of patients. Rates of hypertension (35% vs. 15%) and elevated aspartate aminotransferase (23% vs. 8%) were higher with intermittent dosing. In both patients with high baseline tumor phospho-MET (pMET), the pMET: total MET protein ratio decreased with foretinib treatment.
Conclusion: These results indicate that few gastric carcinomas are driven solely by MET and VEGFR2, and underscore the diverse molecular oncogenesis of this disease. Despite evidence of MET inhibition by foretinib, single-agent foretinib lacked efficacy in unselected patients with metastatic gastric cancer.
C1 [Shah, Manish A.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA.
[Wainberg, Zev A.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Catenacci, Daniel V. T.] Univ Chicago, Chicago, IL 60637 USA.
[Hochster, Howard S.] Yale Univ, New Haven, CT USA.
[Ford, James; Kunz, Pamela] Stanford Univ, Stanford, CA 94305 USA.
[Lee, Fa-Chyi] Univ New Mexico, Albuquerque, NM 87131 USA.
[Kallender, Howard; Martin, Anne-Marie; Liu, Yuan; Gagnon, Robert; Liu, Li] GlaxoSmithKline, Collegeville, PA USA.
[Cecchi, Fabiola; Rabe, Daniel C.; Bottaro, Donald P.] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Keer, Harold] Exelixis, San Francisco, CA USA.
[Bonate, Peter; Gilmer, Tona] GlaxoSmithKline, Res Triangle Pk, NC USA.
RP Shah, MA (reprint author), New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA.
EM mas9313@med.cornell.edu
RI Bottaro, Donald/F-8550-2010;
OI Bottaro, Donald/0000-0002-5057-5334; Cecchi, Franco/0000-0002-2035-5621
FU GlaxoSmithKline
FX Funding for this study was provided by GlaxoSmithKline. The funders were
intimately involved in study design, data collection, and analysis. They
had no role in the decision to publish, but they were involved in
manuscript preparation.
NR 36
TC 76
Z9 81
U1 2
U2 10
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 MAR 14
PY 2013
VL 8
IS 3
AR e54014
DI 10.1371/journal.pone.0054014
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109YM
UT WOS:000316407400003
PM 23516391
ER
PT J
AU Misteli, T
AF Misteli, Tom
TI The Cell Biology of Genomes: Bringing the Double Helix to Life
SO CELL
LA English
DT Article
ID STOCHASTIC GENE-EXPRESSION; ORGANIZATION; CHROMATIN
AB The recent ability to routinely probe genome function at a global scale has revolutionized our view of genomes. One of the most important realizations from these approaches is that the functional output of genomes is affected by the nuclear environment in which they exist. Integration of sequence information with molecular and cellular features of the genome promises a fuller understanding of genome function.
C1 NCI, NIH, Bethesda, MD 20892 USA.
RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM mistelit@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH),
NCI, Center for Cancer Research
FX Due to space limitations, mostly review articles were cited. Work in the
author's laboratory is supported by the Intramural Research Program of
the National Institutes of Health (NIH), NCI, Center for Cancer
Research.
NR 13
TC 31
Z9 31
U1 2
U2 26
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD MAR 14
PY 2013
VL 152
IS 6
BP 1209
EP 1212
DI 10.1016/j.cell.2013.02.048
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 107CO
UT WOS:000316192500002
PM 23498929
ER
PT J
AU Lenoir-Wijnkoop, I
Jones, PJ
Uauy, R
Segal, L
Milner, J
AF Lenoir-Wijnkoop, I.
Jones, P. J.
Uauy, R.
Segal, L.
Milner, J.
TI Nutrition economics - food as an ally of public health
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE Nutrition economics; Health economics; Public health; Cost-effectiveness
ID DAIRY CONSUMPTION; MYOCARDIAL-INFARCTION; CHILD UNDERNUTRITION;
MEDITERRANEAN DIET; COLORECTAL-CANCER; MEAT CONSUMPTION; RISK; TRENDS;
INTERVENTIONS; CONSEQUENCES
AB Non-communicable diseases (NCD) are a major and increasing contributor to morbidity and mortality in developed and developing countries. Much of the chronic disease burden is preventable through modification of lifestyle behaviours, and increased attention is being focused on identifying and implementing effective preventative health strategies. Nutrition has been identified as a major modifiable determinant of NCD. The recent merging of health economics and nutritional sciences to form the nascent discipline of nutrition economics aims to assess the impact of diet on health and disease prevention, and to evaluate options for changing dietary choices, while incorporating an understanding of the immediate impacts and downstream consequences. In short, nutrition economics allows for generation of policy-relevant evidence, and as such the discipline is a crucial partner in achieving better population nutritional status and improvements in public health and wellness. The objective of the present paper is to summarise presentations made at a satellite symposium held during the 11th European Nutrition Conference, 28 October 2011, where the role of nutrition and its potential to reduce the public health burden through alleviating undernutrition and nutrition deficiencies, promoting better-quality diets and incorporating a role for functional foods were discussed.
C1 [Lenoir-Wijnkoop, I.] Danone Res, Sci Affairs, RD 128, F-91767 Palaiseau, France.
[Lenoir-Wijnkoop, I.] Univ Utrecht, Dept Pharmaceut Sci, Utrecht, Netherlands.
[Jones, P. J.] Univ Manitoba, Richardson Ctr Funct Foods & Nutraceut, Winnipeg, MB, Canada.
[Uauy, R.] Univ Chile, INTA, Inst Nutr, Santiago, Chile.
[Segal, L.] Univ S Australia, Sansom Inst Hlth Res, Hlth Econ & Social Policy Grp, Adelaide, SA 5001, Australia.
[Milner, J.] NCI, Nutr Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Lenoir-Wijnkoop, I (reprint author), Danone Res, Sci Affairs, RD 128, F-91767 Palaiseau, France.
EM irene.lenoir@danone.com
RI Segal, Leonie/B-2357-2009;
OI Segal, Leonie/0000-0002-6391-6791; Jones, Peter/0000-0001-5887-2846
FU Danone Institute International; Danone Research
FX The present paper summarises presentations made at a satellite symposium
held at the 11th European Nutrition Conference, 28 October 2011, which
was made possible by an unrestricted grant from Danone Institute
International. Writing and editorial assistance were provided by Lisa
Buttle, of Chill Pill Media. This was contracted and funded by Danone
Research. The authors have declared that they have no conflicting
interests. I. L.-W. is an employee of Danone Research.
NR 39
TC 10
Z9 11
U1 6
U2 63
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
EI 1475-2662
J9 BRIT J NUTR
JI Br. J. Nutr.
PD MAR 14
PY 2013
VL 109
IS 5
BP 777
EP 784
DI 10.1017/S0007114512005107
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 097EL
UT WOS:000315456700001
PM 23339933
ER
PT J
AU Wang, PY
Ma, WZ
Park, JY
Celi, FS
Arena, R
Choi, JW
Ali, QA
Tripodi, DJ
Zhuang, J
Lago, CU
Strong, LC
Talagala, SL
Balaban, RS
Kang, JG
Hwang, PM
AF Wang, Ping-yuan
Ma, Wenzhe
Park, Joon-Young
Celi, Francesco S.
Arena, Ross
Choi, Jeong W.
Ali, Qais A.
Tripodi, Dotti J.
Zhuang, Jie
Lago, Cory U.
Strong, Louise C.
Talagala, S. Lalith
Balaban, Robert S.
Kang, Ju-Gyeong
Hwang, Paul M.
TI Increased Oxidative Metabolism in the Li-Fraumeni Syndrome
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID MITOCHONDRIAL METABOLISM; MUSCLE; CANCER; APOPTOSIS; EXERCISE
AB There is growing evidence that alterations in metabolism may contribute to tumorigenesis. Here, we report on members of families with the Li-Fraumeni syndrome who carry germline mutations in TP53, the gene encoding the tumor-suppressor protein p53. As compared with family members who are not carriers and with healthy volunteers, family members with these mutations have increased oxidative phosphorylation of skeletal muscle. Basic experimental studies of tissue samples from patients with the Li-Fraumeni syndrome and a mouse model of the syndrome support this in vivo finding of increased mitochondrial function. These results suggest that p53 regulates bioenergetic homeostasis in humans. (Funded by the National Heart, Lung, and Blood Institute and the National Institutes of Health; ClinicalTrials.govnumber, NCT00406445.)
C1 [Wang, Ping-yuan; Ma, Wenzhe; Choi, Jeong W.; Ali, Qais A.; Tripodi, Dotti J.; Zhuang, Jie; Lago, Cory U.; Balaban, Robert S.; Kang, Ju-Gyeong; Hwang, Paul M.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Celi, Francesco S.] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Talagala, S. Lalith] NINDS, NIH, Bethesda, MD 20892 USA.
[Park, Joon-Young] Temple Univ, Philadelphia, PA 19122 USA.
[Arena, Ross] Univ New Mexico, Albuquerque, NM 87131 USA.
[Strong, Louise C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Hwang, PM (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10CRC 5-5330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hwangp@nhlbi.nih.gov
RI Arena, Ross/A-3141-2008
OI Arena, Ross/0000-0002-6675-1996
FU Division of Intramural Research, National Heart, Lung, and Blood
Institute; National Institutes of Health Bench-to-Bedside Award;
National Heart, Lung, and Blood Institute; National Institutes of Health
FX Supported by the Division of Intramural Research, National Heart, Lung,
and Blood Institute and by a National Institutes of Health
Bench-to-Bedside Award (to Drs. Hwang and Strong).; Funded by the
National Heart, Lung, and Blood Institute and the National Institutes of
Health.
NR 26
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U1 1
U2 14
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 MAR 14
PY 2013
VL 368
IS 11
BP 1027
EP 1032
DI 10.1056/NEJMoa1214091
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 104HF
UT WOS:000315982100009
PM 23484829
ER
PT J
AU Das, SR
Hensley, SE
Ince, WL
Brooke, CB
Subba, A
Delboy, MG
Russ, G
Gibbs, JS
Bennink, JR
Yewdell, JW
AF Das, Suman R.
Hensley, Scott E.
Ince, William L.
Brooke, Christopher B.
Subba, Anju
Delboy, Mark G.
Russ, Gustav
Gibbs, James S.
Bennink, Jack R.
Yewdell, Jonathan W.
TI Defining Influenza A Virus Hemagglutinin Antigenic Drift by Sequential
Monoclonal Antibody Selection
SO CELL HOST & MICROBE
LA English
DT Article
ID RECEPTOR SPECIFICITY; GLYCOPROTEIN; EVOLUTION; REPERTOIRE; DYNAMICS;
MUTANTS; DISEASE; MICE
AB Human influenza A virus (IAV) vaccination is limited by "antigenic drift," rapid antibody-driven escape reflecting amino acid substitutions in the globular domain of hemagglutinin (HA), the viral attachment protein. To better understand drift, we used anti-hemagglutinin monoclonal Abs (mAbs) to sequentially select IAV escape mutants. Twelve selection steps, each resulting in a single amino acid substitution in the hemagglutinin globular domain, were required to eliminate antigenicity defined by monoclonal or polyclonal Abs. Sequential mutants grow robustly, showing the structural plasticity of HA, although several hemagglutinin substitutions required an epistatic substitution in the neuraminidase glycoprotein to maximize growth. Selecting escape mutants from parental versus sequential variants with the same mAb revealed distinct escape repertoires, attributed to contextual changes in antigenicity and the mutation landscape. Since each hemagglutinin mutation potentially sculpts future mutation space, drift can follow many stochastic paths, undermining its unpredictability and underscoring the need for drift-insensitive vaccines.
C1 [Das, Suman R.; Hensley, Scott E.; Ince, William L.; Brooke, Christopher B.; Gibbs, James S.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
[Das, Suman R.; Subba, Anju; Delboy, Mark G.] J Craig Venter Inst, Infect Dis Grp, Rockville, MD 20850 USA.
[Das, Suman R.] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
[Russ, Gustav] Slovak Acad Sci, Inst Virol, Bratislava 84505, Slovakia.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
EM jyewdell@niaid.nih.gov
FU NIAID; Department of Health and Human Services [HHSN272200900007C]; NIH;
JCVI internal start-up fund; Division of Intramural Research, NIAID
FX We thank Glennys Reynoso for providing outstanding technical assistance.
We thank Dr. Walter Gerhard for his generous gift of the large panel of
mAbs and viruses. We thank Dr. Adolfo Garcia-Sastre and Dr. David
Wentworth for kindly providing eight-plasmid reverse-genetics plasmid to
rescue WT and mutant viruses. We thank Dr. Zhiping Ye for providing
ferret anti-sera to PR8 virus. The sequencing of the whole genome of the
SEQ-variants was done at JCVI, which is one of the Genomic Sequencing
Center of Infectious Diseases (GSCID) and has been funded with federal
funds from the NIAID, NIH, and Department of Health and Human Services
under contract number HHSN272200900007C. S. R. D. is supported by JCVI
internal start-up fund. J. W. Y. and J. R. B. are generously supported
by the Division of Intramural Research, NIAID. S. R. D., S. E. H., W. L.
I., G. R., J. R. B., and J. W. Y. conceived of and designed experiments.
S. R. D., S. E. H., W. L. I., C. B. B., A. S., M. G. D., G. R., and J.
S. G. performed experiments. S. R. D., S. E. H., W. L. I., C. B. B., A.
S., M. G. D., G. R., J. R. B., and J. W. Y. analyzed data. S. R. D. and
J. W. Y. wrote the manuscript.
NR 37
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U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD MAR 13
PY 2013
VL 13
IS 3
BP 314
EP 323
DI 10.1016/j.chom.2013.02.008
PG 10
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AA1IS
UT WOS:000330850400012
PM 23498956
ER
PT J
AU Lewis, NS
Javakhishvili, Z
Russell, CA
Machablishvili, A
Lexmond, P
Verhagen, JH
Vuong, O
Onashvili, T
Donduashvili, M
Smith, DJ
Fouchier, RAM
AF Lewis, Nicola S.
Javakhishvili, Zurab
Russell, Colin A.
Machablishvili, Ann
Lexmond, Pascal
Verhagen, Josanne H.
Oanh Vuong
Onashvili, Tinatin
Donduashvili, Marina
Smith, Derek J.
Fouchier, Ron A. M.
TI Avian Influenza Virus Surveillance in Wild Birds in Georgia: 2009-2011
SO PLOS ONE
LA English
DT Article
ID BLACK-HEADED GULLS; A VIRUS; HEMAGGLUTININ
AB The Caucasus, at the border of Europe and Asia, is important for migration and over-wintering of wild waterbirds. Three flyways, the Central Asian, East Africa-West Asia, and Mediterranean/Black Sea flyways, converge in the Caucasus region. Thus, the Caucasus region might act as a migratory bridge for influenza virus transmission when birds aggregate in high concentrations in the post-breeding, migrating and overwintering periods. Since August 2009, we have established a surveillance network for influenza viruses in wild birds, using five sample areas geographically spread throughout suitable habitats in both eastern and western Georgia. We took paired tracheal and cloacal swabs and fresh feces samples. We collected 8343 swabs from 76 species belonging to 17 families in 11 orders of birds, of which 84 were real-time RT-PCR positive for avian influenza virus (AIV). No highly pathogenic AIV (HPAIV) H5 or H7 viruses were detected. The overall AIV prevalence was 1.6%. We observed peak prevalence in large gulls during the autumn migration (5.3-9.8%), but peak prevalence in Black-headed Gulls in spring (4.2-13%). In ducks, we observed increased AIV prevalence during the autumn post-moult aggregations and migration stop-over period (6.3%) but at lower levels to those observed in other more northerly post-moult areas in Eurasia. We observed another prevalence peak in the overwintering period (0.14-5.9%). Serological and virological monitoring of a breeding colony of Armenian Gulls showed that adult birds were seropositive on arrival at the breeding colony, but juveniles remained serologically and virologically negative for AIV throughout their time on the breeding grounds, in contrast to gull AIV data from other geographic regions. We show that close phylogenetic relatives of viruses isolated in Georgia are sourced from a wide geographic area throughout Western and Central Eurasia, and from areas that are represented by multiple different flyways, likely linking different host sub-populations.
C1 [Lewis, Nicola S.; Russell, Colin A.; Smith, Derek J.] Univ Cambridge, Dept Zool, Cambridge, England.
[Lexmond, Pascal; Verhagen, Josanne H.; Oanh Vuong; Smith, Derek J.; Fouchier, Ron A. M.] Erasmus MC, Dept Virol, Rotterdam, Netherlands.
[Lexmond, Pascal; Verhagen, Josanne H.; Oanh Vuong; Smith, Derek J.; Fouchier, Ron A. M.] Erasmus MC, Natl Influenza Ctr, Rotterdam, Netherlands.
[Russell, Colin A.; Smith, Derek J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Javakhishvili, Zurab] Ilia State Univ, Inst Ecol, Tbilisi, Rep of Georgia.
[Machablishvili, Ann] Ivane Javakhishvili Tbilisi State Univ, Tbilisi, Rep of Georgia.
[Machablishvili, Ann] Natl Ctr Dis Control, Influenza Sect, Tbilisi, Rep of Georgia.
[Onashvili, Tinatin; Donduashvili, Marina] Lab Minist Agr, Tbilisi, Rep of Georgia.
RP Lewis, NS (reprint author), Univ Cambridge, Dept Zool, Cambridge, England.
EM nsl25@cam.ac.uk
RI Fouchier, Ron/A-1911-2014;
OI Fouchier, Ron/0000-0001-8095-2869; Russell, Colin/0000-0002-2113-162X;
Tripp, Ralph/0000-0002-2924-9956
FU Wellcome Trust Fellowship [WT089235MF]; NIAID-NIH "NIAID Centres of
Excellence for Influenza Research and Surveillance'' [HHSN266200700010C]
FX This work was supported by a Wellcome Trust Fellowship WT089235MF
http://www.wellcome.ac.uk/index.htm and by NIAID-NIH contract No.
HHSN266200700010C "NIAID Centres of Excellence for Influenza Research
and Surveillance''
http://www.niaid.nih.gov/LabsAndResources/resources/ceirs/Pages/crip.asp
x. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 22
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U1 1
U2 38
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 MAR 13
PY 2013
VL 8
IS 3
AR e58534
DI 10.1371/journal.pone.0058534
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 115YY
UT WOS:000316849200081
PM 23516501
ER
PT J
AU Mahnke, YD
Song, KM
Sauer, MM
Nason, MC
Giret, MTM
Carvalho, KI
Costa, PR
Roederer, M
Kallas, EG
AF Mahnke, Yolanda D.
Song, Kaimei
Sauer, Mariana M.
Nason, Martha C.
Giret, Maria Teresa M.
Carvalho, Karina I.
Costa, Priscilla R.
Roederer, Mario
Kallas, Esper G.
TI Early immunologic and virologic predictors of clinical HIV-1 disease
progression
SO AIDS
LA English
DT Article
DE CD38; cell-associated viral load; immunophenotyping; prognosis;
progression; T-cell activation
ID CD8(+) T-CELLS; VIRAL LOAD; TYPE-1 INFECTION; FOLLOW-UP; SET-POINT;
CD4(+); RESPONSES; ACTIVATION; SURVIVAL; VIREMIA
AB Objective: To identify early determinants of HIV-1 disease progression, which could potentially enable individualized patient treatment, and provide correlates of progression applicable as reference phenotypes to evaluate breakthrough infections in vaccine development.
Design: High-throughput technologies were employed to interrogate multiple parameters on cryopreserved, retrospective peripheral blood mononuclear cell (PBMC) samples from 51 individuals from Sao Paulo, Brazil, obtained within 1 year of diagnosing early Clade B HIV-1 infection. Fast Progressors, Slow Progressors, and Controllers were identified based on a 2-year clinical follow-up.
Methods: Phenotypic and functional T-cell parameters were tested by flow cytometry and qPCR to identify potential early determinants of subsequent HIV-1 disease progression.
Results: Major differences were observed between Controllers and Progressors, especially in cell-associated viral load (CAVL), the differentiation pattern and CD38 expression of CD8(+) T cells, and the cytokine pattern and activation phenotype of HIV-1-specific CD8(+) T cells. Despite remarkably few other differences between the two Progressor groups, the CAVL had predictive power independent of plasma viral load.
Conclusion: Analysis of three parameters (% CD38(+)CD8(+) T cells, total CAVL,% CCR5(+) CD8(+) T cells) was sufficient to predict subsequent disease progression (P < 0.001). Use of such prognostic correlates may be crucial when early CD4(+) T-cell counts and plasma viral load levels fail to discriminate among groups with differing subsequent clinical progression. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins AIDS 2013, 27:697-706
C1 [Mahnke, Yolanda D.; Song, Kaimei; Roederer, Mario] NIAID, ImmunoTechnol Sect, VRC, NIH, Bethesda, MD 20892 USA.
[Sauer, Mariana M.; Giret, Maria Teresa M.; Carvalho, Karina I.; Costa, Priscilla R.; Kallas, Esper G.] Univ Sao Paulo, Sch Med, Div Clin Immunol & Allergy, Sao Paulo, Brazil.
[Nason, Martha C.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Giret, Maria Teresa M.] Univ Florida, Miller Sch Med, Story Lab 2, Miami, FL USA.
RP Mahnke, YD (reprint author), 40 Convent Dr,Rm 5608, Bethesda, MD 20892 USA.
EM mahnkey@mail.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Brazilian Program
for STD and AIDS, Ministry of Health [914/BRA/3014-UNESCO/Kallas]; Sao
Paulo City Health Department [2004-0.168.922-7/Kallas]; Fundacao de
Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2004/15856-9,
2006/50096-0]
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health; the Brazilian Program for STD and AIDS, Ministry
of Health (grant number 914/BRA/3014-UNESCO/Kallas); the Sao Paulo City
Health Department (grant number 2004-0.168.922-7/Kallas); and the
Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) (grant
numbers 2004/15856-9 and 2006/50096-0). The funding bodies had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 35
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U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD MAR 13
PY 2013
VL 27
IS 5
BP 697
EP 706
DI 10.1097/QAD.0b013e32835ce2e9
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 098CY
UT WOS:000315524700003
PM 23211771
ER
PT J
AU Wong, WT
AF Wong, Wai T.
TI Microglial aging in the healthy CNS: phenotypes, drivers, and
rejuvenation
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Review
DE microglia; aging; priming; neurodegeneration; rejuvenation;
inflammation; activation; senescence
ID LONG-TERM POTENTIATION; ADULT HIPPOCAMPAL NEUROGENESIS;
CENTRAL-NERVOUS-SYSTEM; AMYOTROPHIC-LATERAL-SCLEROSIS;
ALZHEIMERS-DISEASE BRAIN; NEURAL PRECURSOR CELLS; TRANSCRIPTION
FACTOR-A; AGE-RELATED DECLINE; ACTIVATION IN-VIVO; RAT-BRAIN
AB Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and age-related macular degeneration (AMD), share two characteristics in common: (1) a disease prevalence that increases markedly with advancing age, and (2) neuroinflammatory changes in which microglia, the primary resident immune cell of the CNS, feature prominently. These characteristics have led to the hypothesis that pathogenic mechanisms underlying age-related neurodegenerative disease involve aging changes in microglia. If correct, targeting features of microglial senescence may constitute a feasible therapeutic strategy. This review explores this hypothesis and its implications by considering the current knowledge on how microglia undergo change during aging and how the emergence of these aging phenotypes relate to significant alterations in microglial function. Evidence and theories on cellular mechanisms implicated in driving senescence in microglia are reviewed, as are rejuvenative measures and strategies that aim to reverse or ameliorate the aging microglial phenotype. Understanding and controlling microglial aging may represent an opportunity for elucidating disease mechanisms and for formulating novel therapies.
C1 NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bethesda, MD 20892 USA.
RP Wong, WT (reprint author), NEI, Unit Neuron Glia Interact Retinal Dis, NIH, 6 Ctr Dr,6-217, Bethesda, MD 20892 USA.
EM wongw@nei.nih.gov
RI Wong, Wai/B-6118-2017
OI Wong, Wai/0000-0003-0681-4016
FU National Eye Institute Intramural Research Program; Macular Degeneration
Research (MDR); BrightFocus Foundation
FX Research in our laboratory is supported by the National Eye Institute
Intramural Research Program. Acknowledgment is made for grant support to
the donors of Macular Degeneration Research (MDR), a program of the
American Health Assistance Foundation (AHAF, now the BrightFocus
Foundation).
NR 194
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U1 2
U2 27
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5102
J9 FRONT CELL NEUROSCI
JI Front. Cell. Neurosci.
PD MAR 13
PY 2013
VL 7
AR 22
DI 10.3389/fncel.2013.00022
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 111TQ
UT WOS:000316544100001
PM 23493481
ER
PT J
AU He, BJ
AF He, Biyu J.
TI Spontaneous and Task-Evoked Brain Activity Negatively Interact
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID EVENT-RELATED RESPONSES; TO-TRIAL VARIABILITY; CAT VISUAL-CORTEX;
CORTICAL-NEURONS; ACTIVITY FLUCTUATIONS; NEURAL VARIABILITY; SENSORY
RESPONSES; DECISION-MAKING; BARREL CORTEX; BALLOON MODEL
AB A widely held assumption is that spontaneous and task-evoked brain activity sum linearly, such that the recorded brain response in each single trial is the algebraic sum of the constantly changing ongoing activity and the stereotypical evoked activity. Using functional magnetic resonance imaging signals acquired from normal humans, we show that this assumption is invalid. Across widespread cortices, evoked activity interacts negatively with ongoing activity, such that higher prestimulus baseline results in less activation or more deactivation. As a consequence of this negative interaction, trial-to-trial variability of cortical activity decreases following stimulus onset. We further show that variability reduction follows overlapping but distinct spatial pattern from that of task-activation/deactivation and it contains behaviorally relevant information. These results favor an alternative perspective to the traditional dichotomous framework of ongoing and evoked activity. That is, to view the brain as a nonlinear dynamical system whose trajectory is tighter when performing a task. Further, incoming sensory stimuli modulate the brain's activity in a manner that depends on its initial state. We propose that across-trial variability may provide a new approach to brain mapping in the context of cognitive experiments.
C1 [He, Biyu J.] NINDS, NIH, Bethesda, MD 20892 USA.
RP He, BJ (reprint author), 10 Ctr Dr,Bldg 10,Room B1D728, Bethesda, MD 20892 USA.
EM biyu.he@nih.gov
OI He, Biyu/0000-0003-1549-1351
FU Intramural Research Program of the National Institutes of
Health/National Institute of Neurological Disorders and Stroke
FX This research was supported by the Intramural Research Program of the
National Institutes of Health/National Institute of Neurological
Disorders and Stroke. I thank Marc Raichle for sharing the data used in
this study; Michael Berry, Alan Koretsky, and Afonso Silva for
discussions; and David Leopold, Alex Martin, and Peter Bandettini for
comments on a previous draft of the manuscript.
NR 74
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U1 0
U2 23
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 13
PY 2013
VL 33
IS 11
BP 4672
EP 4682
DI 10.1523/JNEUROSCI.2922-12.2013
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 106CO
UT WOS:000316119200005
PM 23486941
ER
PT J
AU Cimino, JJ
AF Cimino, James J.
TI Improving the Electronic Health Record-Are Clinicians Getting What They
Wished For?
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID MEDICAL RECORDS; TEACH; GUIDE
C1 [Cimino, James J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20852 USA.
RP Cimino, JJ (reprint author), NIH, 10 Ctr Dr, Bethesda, MD 20852 USA.
EM james.cimino@nih.gov
OI Cimino, James/0000-0003-4101-1622
FU Intramural NIH HHS [Z99 CL999999]
NR 9
TC 27
Z9 27
U1 0
U2 6
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 13
PY 2013
VL 309
IS 10
BP 991
EP 992
DI 10.1001/jama.2013.890
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 103SH
UT WOS:000315938700025
PM 23483171
ER
PT J
AU Clair, C
Rigotti, NA
Porneala, B
Fox, CS
D'Agostino, RB
Pencina, MJ
Meigs, JB
AF Clair, Carole
Rigotti, Nancy A.
Porneala, Bianca
Fox, Caroline S.
D'Agostino, Ralph B., Sr.
Pencina, Michael J.
Meigs, James B.
TI Association of Smoking Cessation and Weight Change With Cardiovascular
Disease Among Adults With and Without Diabetes
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID RANDOMIZED CLINICAL-TRIAL; CORONARY-HEART-DISEASE; CIGARETTE-SMOKING;
UNITED-STATES; RISK-FACTORS; MORTALITY; MELLITUS; WOMEN; POPULATION;
OUTCOMES
AB Importance Smoking cessation reduces the risks of cardiovascular disease (CVD), but weight gain that follows quitting smoking may weaken the CVD benefit of quitting.
Objective To test the hypothesis that weight gain following smoking cessation does not attenuate the benefits of smoking cessation among adults with and without diabetes.
Design, Setting, and Participants Prospective community-based cohort study using data from the Framingham Offspring Study collected from 1984 through 2011. At each 4-year examination, self-reported smoking status was assessed and categorized as smoker, recent quitter (-4 years), long-term quitter (-4 years), and nonsmoker. Pooled Cox proportional hazards models were used to estimate the association between quitting smoking and 6-year CVD events and to test whether 4-year change in weight following smoking cessation modified the association between smoking cessation and CVD events.
Main Outcome Measure Incidence over 6 years of total CVD events, comprising coronary heart disease, cerebrovascular events, peripheral artery disease, and congestive heart failure.
Results After a mean follow-up of 25 (SD, 9.6) years, 631 CVD events occurred among 3251 participants. Median 4-year weight gain was greater for recent quitters without diabetes (2.7 kg [interquartile range {IQR}, -0.5 to 6.4]) and with diabetes (3.6 kg [IQR, -1.4 to 8.2]) than for long-term quitters (0.9 kg [IQR, -1.4 to 3.2] and 0.0 kg [IQR, -3.2 to 3.2], respectively, P < .001). Among participants without diabetes, age-and sex-adjusted incidence rate of CVD was 5.9 per 100 person-examinations (95% CI, 4.9-7.1) in smokers, 3.2 per 100 person-examinations (95% CI, 2.1-4.5) in recent quitters, 3.1 per 100 person-examinations (95% CI, 2.6-3.7) in long-term quitters, and 2.4 per 100 person-examinations (95% CI, 2.0-3.0) in nonsmokers. After adjustment for CVD risk factors, compared with smokers, recent quitters had a hazard ratio (HR) for CVD of 0.47 (95% CI, 0.23-0.94) and long-term quitters had an HR of 0.46 (95% CI, 0.34-0.63); these associations had only a minimal change after further adjustment for weight change. Among participants with diabetes, there were similar point estimates that did not reach statistical significance.
Conclusions and Relevance In this community-based cohort, smoking cessation was associated with a lower risk of CVD events among participants without diabetes, and weight gain that occurred following smoking cessation did not modify this association. This supports a net cardiovascular benefit of smoking cessation, despite subsequent weight gain. JAMA. 2013;309(10):1014-1021 www.jama.com
C1 [Clair, Carole; Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA.
[Clair, Carole; Rigotti, Nancy A.; Porneala, Bianca; Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA.
[Fox, Caroline S.] NHLBI, NIH, Framingham Heart Study, Framingham, MA USA.
[D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Pencina, Michael J.] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Pencina, Michael J.] Harvard Clin Res Inst, Boston, MA USA.
RP Clair, C (reprint author), Univ Lausanne, Dept Ambulatory Care & Community Med, 44 Bugnon Ave, CH-1011 Lausanne, Switzerland.
EM carole.willi@gmail.com
RI Clair, Carole/D-9786-2014
OI Clair, Carole/0000-0001-5281-0943
FU UpToDate Inc; Swiss National Science Foundation [PBLAP3-127728/1]; SICPA
Foundation; National Heart, Lung, and Blood Institute (NHLBI)
[5K24HL4440-10]; National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) [K24 DK080140]; Swiss National Science Foundation;
NHLBI Framingham Heart Study [N01-HC-25195]
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Dr Rigotti reported serving as an
unpaid consultant to Pfizer and Allere Wellbeing Inc; conducting
research projects sponsored by Pfizer and Nabi Biopharmaceuticals; and
receiving royalties from UpToDate Inc for chapters related to smoking
cessation. Dr Pencina reported serving as a data and safety monitoring
board member for Thoracos. No other authors reported disclosures.; Dr
Clair was supported by a grant from the Swiss National Science
Foundation (PBLAP3-127728/1) and by a grant from the SICPA Foundation.
Dr Rigotti was supported by National Heart, Lung, and Blood Institute
(NHLBI) grant 5K24HL4440-10. Dr Meigs was supported by National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant
K24 DK080140.; The Swiss National Science Foundation, SICPA Foundation,
and NIDDK had no role in the design and conduct of the study; the
collection, management, analysis, and interpretation of the data; or the
preparation, review, or approval of the manuscript. The Framingham Heart
Study is supported by the NHLBI Framingham Heart Study (contract
N01-HC-25195 [Drs D'Agostino and Pencina]). The NHLBI approved the
manuscript.
NR 26
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Z9 73
U1 3
U2 26
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 13
PY 2013
VL 309
IS 10
BP 1014
EP 1021
DI 10.1001/jama.2013.1644
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 103SH
UT WOS:000315938700030
PM 23483176
ER
PT J
AU Purcell, RH
Engle, RE
Govindarajan, S
Herbert, R
St Claire, M
Elkins, WR
Cook, A
Shaver, C
Beauregard, M
Swerczek, J
Emerson, SU
AF Purcell, Robert H.
Engle, Ronald E.
Govindarajan, Sugantha
Herbert, Richard
St Claire, Marisa
Elkins, William R.
Cook, Anthony
Shaver, Charlene
Beauregard, Michelle
Swerczek, Joanne
Emerson, Suzanne U.
TI Pathobiology of hepatitis E: lessons learned from primate models
SO EMERGING MICROBES & INFECTIONS
LA English
DT Article
DE HEV; host range; nonhuman primates; virulence; genotypes
ID NON-B-HEPATITIS; E VIRUS; IGG SEROPREVALENCE; UNITED-STATES; ANTI-HEV;
NON-A; INFECTION; TRANSMISSION; STRAINS; DISEASE
AB Like the other hepatitis viruses, hepatitis E virus (HEV) has been difficult to study because of limitations in cell culture systems and small animal models. Much of what we know has come from epidemiological studies in developing countries and, more recently, in industrialized countries. However, the epidemiology is very different in these two settings: hepatitis E in developing countries is epidemic as well as sporadic, principally water-borne, most likely to cause disease in older children and young adults and relatively severe, especially in pregnant women; in industrialized countries the disease is sporadic, principally food-borne, most common in the elderly and probably associated with mostly inapparent infections. These differences are believed to be genotypically determined. To examine the biological parameters of hepatitis E, we have studied HEV infections in nonhuman primates, which are surrogates of man. Infections with HEV genotypes 1-3 were compared in rhesus and cynomolgus macaques and chimpanzees. In general, the biological characteristics of the different HEV genotypes mirrored their epidemiological characteristics.
C1 [Purcell, Robert H.; Engle, Ronald E.; Herbert, Richard; St Claire, Marisa; Elkins, William R.; Beauregard, Michelle; Swerczek, Joanne; Emerson, Suzanne U.] NIAID, NIH, Bethesda, MD 20892 USA.
[Govindarajan, Sugantha] Univ So Calif, Rancho Los Amigos Hosp, Downey, CA 90242 USA.
[Cook, Anthony; Shaver, Charlene] Bioqual Inc, Rockville, MD 20850 USA.
RP Emerson, SU (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM semerson@niaid.nih.gov
FU intramural research program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX The authors are grateful for the excellent statistical support of Jing
Qin, Biostatistics Research Branch, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. This study was
supported by the intramural research program of the National Institute
of Allergy and Infectious Diseases, National Institutes of Health. The
authors have nothing to declare.
NR 27
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U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2222-1751
J9 EMERG MICROBES INFEC
JI Emerg. Microbes Infect.
PD MAR 13
PY 2013
VL 2
AR e9
DI 10.1038/emi2013.9
PG 6
WC Immunology; Microbiology
SC Immunology; Microbiology
GA AL5MO
UT WOS:000339178100001
PM 26038457
ER
PT J
AU Ferguson, JF
Patel, PN
Shah, RY
Mulvey, CK
Gadi, R
Nijjar, PS
Usman, HM
Mehta, NN
Shah, R
Master, SR
Propert, KJ
Reilly, MP
AF Ferguson, Jane F.
Patel, Parth N.
Shah, Rhia Y.
Mulvey, Claire K.
Gadi, Ram
Nijjar, Prabhjot S.
Usman, Haris M.
Mehta, Nehal N.
Shah, Rachana
Master, Stephen R.
Propert, Kathleen J.
Reilly, Muredach P.
TI Race and gender variation in response to evoked inflammation
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; TOLL-LIKE RECEPTOR-4;
INSULIN-RESISTANCE; METABOLIC ENDOTOXEMIA; SEVERE SEPSIS; IN-VIVO;
ATHEROSCLEROSIS; LIPOPROTEINS; BIOMARKERS
AB Background: Race- and gender-variation in innate immunity may contribute to demographic differences in inflammatory and cardiometabolic disease; yet their influence on dynamic responses during inflammatory stress is poorly understood. Our objective was to examine race and gender influence on the response to experimental endotoxemia.
Methods: The Genetics of Evoked Responses to Niacin and Endotoxemia (GENE) study was designed to investigate regulation of inflammatory and metabolic responses during low-grade endotoxemia (LPS 1 ng/kg intravenously) in healthy individuals (median age 24, IQR=7) of European (EA; n=193, 47% female) and African ancestry (AA; n=101, 59% female).
Results: Baseline clinical, metabolic, and inflammatory biomarkers by race and gender were consistent with epidemiological literature; pre-LPS cytokines (e.g. median (IQR) IL-6, 2.7 (2) vs. 2.1 (2) pg/ml, P=0.001) were higher in AA than EA. In contrast, acute cytokine responses during endotoxemia were lower in AA than EA (e.g. median (IQR) peak IL-1RA, 30 (38) vs. 43 (45) ng/ml P=0.002) as was the induction of hepatic acute-phase proteins (e.g. median (IQR) peak CRP 12.9 (9) vs. 17.4 (12) mg/L P=0.005). Further, baseline levels of cytokines were only weakly correlated with peak inflammatory responses (all r(s) <0.2) both in AA and in EA. There were less pronounced and less consistent differences in the response by gender, with males having a higher AUC for CRP response compared to females (median (IQR) AUC: 185 (112) vs. 155 (118), P=0.02).
Conclusions: We observed lower levels of evoked inflammation in response to endotoxin in AA compared with EA, despite similar or higher baseline levels of inflammatory markers in AA. Our data also suggest that levels of inflammatory biomarkers measured in epidemiological settings might not predict the degree of acute stress-response or risk of diseases characterized by activation of innate immunity.
C1 [Ferguson, Jane F.; Patel, Parth N.; Shah, Rhia Y.; Mulvey, Claire K.; Gadi, Ram; Usman, Haris M.; Mehta, Nehal N.; Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Perelman Sch Med, Smilow Ctr Translat Res 11 136, Philadelphia, PA 19104 USA.
[Nijjar, Prabhjot S.] Univ Minnesota, Sch Med, Div Cardiol, Minneapolis, MN 55455 USA.
[Mehta, Nehal N.] NHLBI, Bethesda, MD 20892 USA.
[Shah, Rachana] Childrens Hosp, Div Pediat Endocrinol, Philadelphia, PA 19104 USA.
[Master, Stephen R.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Propert, Kathleen J.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Ferguson, JF (reprint author), Univ Penn, Cardiovasc Inst, Perelman Sch Med, Smilow Ctr Translat Res 11 136, Bldg 421,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM jfer@mail.med.upenn.edu; muredach@mail.med.upenn.edu
RI Ferguson, Jane/C-7154-2011;
OI Ferguson, Jane/0000-0001-6896-1025; Shah, Rachana/0000-0001-7866-557X
FU National Center for Research Resources, National Institutes of Health
[UL1TR000003]; National Center for Advancing Translational Sciences,
National Institutes of Health [UL1TR000003]; NIH-NHLBI SCCOR Project
[P50-HL-083799]; American Heart Association [12POST11840017];
[RO1-HL-111694]; [RO1-HL-113147]; [RO1-DK-090505]; [UO1-HL-108636];
[K24-HL-107643]
FX The project described was supported by the National Center for Research
Resources and the National Center for Advancing Translational Sciences,
National Institutes of Health, through Grant UL1TR000003 as well as a
NIH-NHLBI SCCOR Project grant (P50-HL-083799) to MPR. JFF is supported
by a postdoctoral fellowship grant from the American Heart Association
(12POST11840017). MPR is also supported by RO1-HL-111694, RO1-HL-113147,
RO1-DK-090505, UO1-HL-108636 and K24-HL-107643. The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the NIH.
NR 43
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U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD MAR 12
PY 2013
VL 11
AR 63
DI 10.1186/1479-5876-11-63
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 133CU
UT WOS:000318115800001
PM 23497455
ER
PT J
AU Akrawinthawong, K
Park, J
Piknova, B
Sibmooh, N
Fucharoen, S
Schechter, AN
AF Akrawinthawong, Krittapoom
Park, Jiwon
Piknova, Barbora
Sibmooh, Nathawut
Fucharoen, Suthat
Schechter, Alan N.
TI A FLOW-CYTOMETRIC ANALYSIS OF THE INHIBITION OF PLATELET REACTIVITY WITH
NITRITE REDUCTION BY DEOXYGENATED ERYTHROCYTES
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 NIDDK, Mol Med Branch, NIH, Bethesda, MD USA.
Mahidol Univ, Fac Med, Siriraj Hosp, Bangkok 10700, Thailand.
NR 0
TC 0
Z9 0
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 MAR 12
PY 2013
VL 61
IS 10
SU S
BP E2067
EP E2067
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555202271
ER
PT J
AU AlGhatrif, M
Strait, J
Morrell, C
Canepa, M
Wright, J
Najjar, S
Ferrucci, L
Lakatta, E
AF AlGhatrif, Majd
Strait, James
Morrell, Christopher
Canepa, Marco
Wright, Jeanette
Najjar, Samer
Ferrucci, Luigi
Lakatta, Edward
TI AGE-ASSOCIATED LONGITUDINAL CHANGES IN ARTERIAL STIFFNESS TRAJECTORIES
AND BLOOD PRESSURE WITHIN INDIVIDUALS OF COMMUNITY DWELLING POPULATION
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 NIA, Baltimore, MD 21224 USA.
Johns Hopkins Sch Med, Baltimore, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
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 MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1381
EP E1381
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201486
ER
PT J
AU Donekal, S
Venkatesh, BA
Kihei, Y
Liu, C
Nacif, M
Armstrong, A
Wu, C
Gomes, AS
Hundley, WG
McClelland, R
Bluemke, D
Lima, JAC
AF Donekal, Sirisha
Venkatesh, Bharath Ambale
Kihei, Yoneyama
Liu, Chia
Nacif, Marcelo
Armstrong, Anderson
Wu, Colin
Gomes, Antoinette S.
Hundley, W. Gregory
McClelland, Robyn
Bluemke, David
Lima, Joao A. C.
TI DETERMINANTS OF TEMPORAL CHANGE IN REGIONAL MYOCARDIAL FUNCTION: THE
MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA)
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Johns Hopkins Univ, Baltimore, MD USA.
NIH, Bethesda, MD 20892 USA.
RI Armstrong, Anderson/G-8407-2012; Ambale Venkatesh, Bharath/F-4941-2016
OI Armstrong, Anderson/0000-0003-3161-8922; Ambale Venkatesh,
Bharath/0000-0002-2330-2373
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E939
EP E939
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201044
ER
PT J
AU Karikkineth, AC
Canepa, M
Elango, P
Strait, JB
Lakatta, EG
Ferrucci, L
AF Karikkineth, Ajoy C.
Canepa, Marco
Elango, Palchamy
Strait, James B.
Lakatta, Edward G.
Ferrucci, Luigi
TI C-REACTIVE PROTEIN AS A PREDICTOR OF INTIMAL MEDIA THICKNESS IN A
HEALTHY COMMUNITY DWELLING POPULATION OF A BROAD AGE RANGE
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Karikkineth, Ajoy C.; Canepa, Marco; Elango, Palchamy; Strait, James B.; Lakatta, Edward G.; Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E2030
EP E2030
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555202234
ER
PT J
AU Mehta, NN
Sheth, NH
Baker, J
Ogdie, A
Raper, A
Saboury, B
Werner, TJ
Thomas, P
VanVoorhees, A
Alavi, A
Torigian, D
Gelfand, J
AF Mehta, Nehal N.
Sheth, Nikhil H.
Baker, Joshua
Ogdie, Alexis
Raper, Anna
Saboury, Babak
Werner, Thomas J.
Thomas, Preethi
VanVoorhees, Abby
Alavi, Abass
Torigian, Drew
Gelfand, Joel
TI A COMPARISON OF VASCULAR INFLAMMATION IN RHEUMATOID ARTHRITIS, PSORIASIS
AND HEALTHY CONTROLS BY FDG-PET/CT: A PILOT STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 NHLBI, Bethesda, MD 20892 USA.
Univ Penn, Philadelphia, NJ USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1056
EP E1056
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201161
ER
PT J
AU Baez, A
Shiloach, J
AF Baez, Antonino
Shiloach, Joseph
TI Escherichia coli avoids high dissolved oxygen stress by activation of
SoxRS and manganese-superoxide dismutase
SO MICROBIAL CELL FACTORIES
LA English
DT Article
DE Oxidative stress; ROS; SoxS; Catalase activity; SOD activity
ID HIGH CELL-DENSITY; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; ANTIOXIDANT
DEFENSES; REGULON; SITE; ACONITASE; GENE; BIOSYNTHESIS; INACTIVATION
AB Background: High concentrations of reactive oxygen species (ROS) were reported to cause oxidative stress to E. coli cells associated with reduced or inhibited growth. The high ROS concentrations described in these reports were generated by exposing the bacteria to H2O2 and superoxide-generating chemicals which are non-physiological growth conditions. However, the effect of molecular oxygen on oxidative stress response has not been evaluated. Since the use of oxygen-enriched air is a common strategy to support high density growth of E. coli, it was important to investigate the effect of high dissolved oxygen concentrations on the physiology and growth of E. coli and the way it responds to oxidative stress.
Results: To determine the effect of elevated oxygen concentrations on the growth characteristics, specific gene expression and enzyme activity in E. coli, the parental and SOD-deficient strain were evaluated when the dissolved oxygen (dO(2)) level was increased from 30% to 300%. No significant differences in the growth parameters were observed in the parental strain except for a temporary decrease of the respiration and acetate accumulation profile. By performing transcriptional analysis, it was determined that the parental strain responded to the oxidative stress by activating the SoxRS regulon. However, following the dO(2) switch, the SOD-deficient strain activated both the SoxRS and OxyR regulons but it was unable to resume its initial growth rate.
Conclusion: The transcriptional analysis and enzyme activity results indicated that when E. coli is exposed to dO(2) shift, the superoxide stress regulator SoxRS is activated and causes the stimulation of the superoxide dismutase system. This enables the E. coli to protect itself from the poisoning effects of oxygen. The OxyR protecting system was not activated, indicating that H2O2 did not increase to stressing levels.
C1 [Baez, Antonino; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
RP Shiloach, J (reprint author), NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
EM yossi@nih.gov
FU intramural program of the National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health
FX Funding was provided by the intramural program of the National Institute
of Diabetes and Digestive and Kidney Diseases, National Institutes of
Health. The authors would like to thank James Imlay (University of
Illinois) for providing the AB1157 and PN134 strains, N. Majdalani (NCI,
NIH) for the scientific advice and Mrs. D. Livnat for critical editorial
assistance.
NR 37
TC 8
Z9 8
U1 1
U2 25
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2859
J9 MICROB CELL FACT
JI Microb. Cell. Fact.
PD MAR 12
PY 2013
VL 12
AR 23
DI 10.1186/1475-2859-12-23
PG 9
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 115DL
UT WOS:000316792700001
PM 23497217
ER
PT J
AU Yeo, M
Berglund, K
Hanna, M
Guo, JU
Kittur, J
Torres, MD
Abramowitz, J
Busciglio, J
Gao, Y
Birnbaumer, L
Liedtke, WB
AF Yeo, Michele
Berglund, Ken
Hanna, Michael
Guo, Junjie U.
Kittur, Jaya
Torres, Maria D.
Abramowitz, Joel
Busciglio, Jorge
Gao, Yuan
Birnbaumer, Lutz
Liedtke, Wolfgang B.
TI Bisphenol A delays the perinatal chloride shift in cortical neurons by
epigenetic effects on the Kcc2 promoter
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID DEVELOPMENTAL SWITCH; PRENATAL EXPOSURE; BRAIN-DEVELOPMENT; GENOME;
MECP2; GABA; NEUROTOXICITY; TRANSCRIPTION; ISCHEMIA; US
AB Bisphenol A (BPA) is a ubiquitous compound that is emerging as a possible toxicant during embryonic development. BPA has been shown to epigenetically affect the developing nervous system, but the molecular mechanisms are not clear. Here we demonstrate that BPA exposure in culture led to delay in the perinatal chloride shift caused by significant decrease in potassium chloride cotransporter 2 (Kcc2) mRNA expression in developing rat, mouse, and human cortical neurons. Neuronal chloride increased correspondingly. Treatment with epigenetic compounds decitabine and trichostatin A rescued the BPA effects as did knockdown of histone deacetylase 1 and combined knockdown histone deacetylase 1 and 2. Furthermore, BPA evoked increase in tangential interneuron migration and increased chloride in migrating neurons. Interestingly. BPA exerted its effect in a sexually dimorphic manner, with a more accentuated effect in females than males. By chromatin immunoprecipitation, we found a significant increase in binding of methyl-CpG binding protein 2 to the "cytosine-phosphate-guanine shores" of the Kcc2 promoter, and decrease in binding of acetylated histone H3K9 surrounding the transcriptional start site. Methyl-CpG binding protein 2-expressing neurons were more abundant resulting from BPA exposure. The sexually dimorphic effect of BPA on Kcc2 expression was also demonstrated in cortical neurons cultured from the offspring of BPA-fed mouse dams. In these neurons and in cortical slices, decitabine was found to rescue the effect of BPA on Kcc2 expression. Overall, our results indicate that BPA can disrupt Kcc2 gene expression through epigenetic mechanisms. Beyond increase in basic understanding, our findings have relevance for identifying unique neurodevelopmental toxicity mechanisms of BPA, which could possibly play a role in pathogenesis of human neurodevelopmental disorders.
C1 [Yeo, Michele; Berglund, Ken; Liedtke, Wolfgang B.] Duke Univ, Dept Med Neurol, Durham, NC 27710 USA.
[Liedtke, Wolfgang B.] Duke Univ, Dept Neurobiol, Durham, NC 27710 USA.
[Hanna, Michael; Torres, Maria D.; Busciglio, Jorge] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92617 USA.
[Guo, Junjie U.; Gao, Yuan] Johns Hopkins Univ, Lieber Inst Brain Dev & Neuroregenerat, Baltimore, MD 21205 USA.
[Guo, Junjie U.; Gao, Yuan] Johns Hopkins Univ, Stem Cell Program, Inst Cell Engn, Baltimore, MD 21205 USA.
[Kittur, Jaya; Abramowitz, Joel; Birnbaumer, Lutz] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Liedtke, Wolfgang B.] Duke Univ, Clin Pain, Durham, NC 27705 USA.
[Liedtke, Wolfgang B.] Duke Univ, Clin Palliat Care, Durham, NC 27705 USA.
RP Birnbaumer, L (reprint author), NIEHS, Neurobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM bimbaul@niehs.nih.gov; wolfgang@neuro.duke.edu
RI Abramowitz, Joel/A-2620-2015
FU Duke University; National Institutes of Health [R21NS066307, HD38466,
AG16573]; intramural funds from the National Institute of Environmental
Health Sciences; Klingenstein Fund
FX This study was supported by funding from Duke University, the
Klingenstein Fund, the National Institutes of Health [R21NS066307 (to
W.B.L) and HD38466 and AG16573 (to J.B.)], and intramural funds from the
National Institute of Environmental Health Sciences (to L.B.).
NR 38
TC 28
Z9 28
U1 6
U2 30
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 MAR 12
PY 2013
VL 110
IS 11
BP 4315
EP 4320
DI 10.1073/pnas.1300959110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107RK
UT WOS:000316238300039
PM 23440186
ER
PT J
AU Liu, X
Duyn, JH
AF Liu, Xiao
Duyn, Jeff H.
TI Time-varying functional network information extracted from brief
instances of spontaneous brain activity
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE instantaneous coactivation; network dynamics; nonstationary
connectivity; resting-state network; clustering analysis
ID RESTING-STATE; DEFAULT NETWORK; SENSORY STIMULATION; CLUSTER-ANALYSIS;
GLOBAL SIGNAL; MOTOR CORTEX; CONNECTIVITY; FLUCTUATIONS; ARCHITECTURE;
DYNAMICS
AB Recent functional magnetic resonance imaging studies have shown that the brain is remarkably active even in the absence of overt behavior, and this activity occurs in spatial patterns that are reproducible across subjects and follow the brain's established functional subdivision. Investigating the distribution of these spatial patterns is an active area of research with the goal of obtaining a better understanding of the neural networks underlying brain function. One intriguing aspect of spontaneous activity is an apparent nonstationarity, or variability of interaction between brain regions. It was recently proposed that spontaneous brain activity may be dominated by brief traces of activity, possibly originating from a neuronal avalanching phenomenon. Such traces may involve different subregions in a network at different times, potentially reflecting functionally relevant relationships that are not captured with conventional data analysis. To investigate this, we examined publicly available functional magnetic resonance imaging data with a dedicated analysis method and found indications that functional networks inferred from conventional correlation analysis may indeed be driven by activity at only a few critical time points. Subsequent analysis of the activity at these critical time points revealed multiple spatial patterns, each distinctly different from the established functional networks. The spatial distribution of these patterns suggests a potential functional relevance.
C1 [Liu, Xiao; Duyn, Jeff H.] NINDS, Adv Magnet Resonance Imaging Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Liu, X (reprint author), NINDS, Adv Magnet Resonance Imaging Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
EM liux15@ninds.nih.gov
RI Liu, Xiao/C-5943-2016
FU Intramural Research Program of the National Institutes of Health,
National Institute of Neurological Disorders and Stroke
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Neurological
Disorders and Stroke.
NR 47
TC 86
Z9 88
U1 3
U2 24
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 MAR 12
PY 2013
VL 110
IS 11
BP 4392
EP 4397
DI 10.1073/pnas.1216856110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107RK
UT WOS:000316238300052
PM 23440216
ER
PT J
AU Innes, CL
Hesse, JE
Palii, SS
Helmink, BA
Holub, AJ
Sleckman, BP
Paules, RS
AF Innes, Cynthia L.
Hesse, Jill E.
Palii, Stela S.
Helmink, Beth A.
Holub, Abigail J.
Sleckman, Barry P.
Paules, Richard S.
TI DNA damage activates a complex transcriptional response in murine
lymphocytes that includes both physiological and cancer-predisposition
programs
SO BMC GENOMICS
LA English
DT Article
DE miR-155; B cells; Ionizing radiation; DNA damage; Double strand breaks;
Transcriptome profiles
ID DOUBLE-STRAND BREAKS; IONIZING-RADIATION; EXPRESSION; GENE;
MICRORNA-155; MIR-155; PROLIFERATION; INFLAMMATION; REQUIREMENT; PATHWAY
AB Background: Double strand (ds) DNA breaks are a form of DNA damage that can be generated from both genotoxic exposures and physiologic processes, can disrupt cellular functions and can be lethal if not repaired properly. Physiologic dsDNA breaks are generated in a variety of normal cellular functions, including the RAG endonuclease-mediated rearrangement of antigen receptor genes during the normal development of lymphocytes. We previously showed that physiologic breaks initiate lymphocyte development-specific transcriptional programs. Here we compare transcriptional responses to physiological DNA breaks with responses to genotoxic DNA damage induced by ionizing radiation.
Results: We identified a central lymphocyte-specific transcriptional response common to both physiologic and genotoxic breaks, which includes many lymphocyte developmental processes. Genotoxic damage causes robust alterations to pathways associated with B cell activation and increased proliferation, suggesting that genotoxic damage initiates not only the normal B cell maturation processes but also mimics activated B cell response to antigenic agents. Notably, changes including elevated levels of expression of Kras and mmu-miR-155 and the repression of Socs1 were observed following genotoxic damage, reflecting induction of a cancer-prone phenotype.
Conclusions: Comparing these transcriptional responses provides a greater understanding of the mechanisms cells use in the differentiation between types of DNA damage and the potential consequences of different sources of damage. These results suggest genotoxic damage may induce a unique cancer-prone phenotype and processes mimicking activated B cell response to antigenic agents, as well as the normal B cell maturation processes.
C1 [Innes, Cynthia L.; Hesse, Jill E.; Palii, Stela S.; Paules, Richard S.] NIEHS, Environm Stress & Canc Grp, Res Triangle Pk, NC 27709 USA.
[Helmink, Beth A.; Holub, Abigail J.; Sleckman, Barry P.] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA.
RP Paules, RS (reprint author), NIEHS, Environm Stress & Canc Grp, POB 12233, Res Triangle Pk, NC 27709 USA.
EM paules@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences; NIH/NIAID [R01
AI047829]
FX The authors would like to thank the members of the NIEHS Microarray Core
facility and the NIEHS Flow Cytometry Core facility for their helpful
service and technical expertise, and the members of the Environmental
Genetics Group at NIEHS for helpful discussions concerning Nrf2
pathways. The authors would also like to thank Drs. Michael Fessler,
Anton Jetten, and Kymberly Gowdy for their helpful comments and
suggestions. This research was supported in part by the Intramural
Research Program of the NIH, National Institute of Environmental Health
Sciences and by a grant to BPS from NIH/NIAID (R01 AI047829).
NR 29
TC 0
Z9 0
U1 0
U2 7
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 MAR 12
PY 2013
VL 14
AR 163
DI 10.1186/1471-2164-14-163
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 109XE
UT WOS:000316403000001
PM 23496831
ER
PT J
AU Walsh, MP
Duncan, B
Larabee, S
Krauss, A
Davis, JPE
Cui, YZ
Kim, SY
Guimond, M
Bachovchin, W
Fry, TJ
AF Walsh, Meghaan P.
Duncan, Brynn
Larabee, Shannon
Krauss, Aviva
Davis, Jessica P. E.
Cui, Yongzhi
Kim, Su Young
Guimond, Martin
Bachovchin, William
Fry, Terry J.
TI Val-BoroPro Accelerates T Cell Priming via Modulation of Dendritic Cell
Trafficking Resulting in Complete Regression of Established Murine
Tumors
SO PLOS ONE
LA English
DT Article
ID FIBROBLAST ACTIVATION PROTEIN; DIPEPTIDYL PEPTIDASE-IV; PHASE-II TRIAL;
CANCER-IMMUNOTHERAPY; ANTITUMOR IMMUNITY; ADAPTIVE IMMUNITY;
SMALL-MOLECULE; LYMPH-NODES; TALABOSTAT; IMMUNOSURVEILLANCE
AB Although tumors naturally prime adaptive immune responses, tolerance may limit the capacity to control progression and can compromise effectiveness of immune-based therapies for cancer. Post-proline cleaving enzymes (PPCE) modulate protein function through N-terminal dipeptide cleavage and inhibition of these enzymes has been shown to have antitumor activity. We investigated the mechanism by which Val-boroPro, a boronic dipeptide that inhibits post-proline cleaving enzymes, mediates tumor regression and tested whether this agent could serve as a novel immune adjuvant to dendritic cell vaccines in two different murine syngeneic murine tumors. In mice challenged with MB49, which expresses the HY antigen complex, T cell responses primed by the tumor with and without Val-boroPro were measured using interferon gamma ELISPOT. Antibody depletion and gene-deficient mice were used to establish the immune cell subsets required for tumor regression. We demonstrate that Val-boroPro mediates tumor eradication by accelerating the expansion of tumor-specific T cells. Interestingly, T cells primed by tumor during Val-boroPro treatment demonstrate increased capacity to reject tumors following adoptive transfer without further treatment of the recipient. Val-boroPro -mediated tumor regression requires dendritic cells and is associated with enhanced trafficking of dendritic cells to tumor draining lymph nodes. Finally, dendritic cell vaccination combined with Val-boroPro treatment results in complete regression of established tumors. Our findings demonstrate that Val-boroPro has antitumor activity and a novel mechanism of action that involves more robust DC trafficking with earlier priming of T cells. Finally, we show that Val-boroPro has potent adjuvant properties resulting in an effective therapeutic vaccine.
C1 [Walsh, Meghaan P.; Duncan, Brynn; Larabee, Shannon; Krauss, Aviva; Davis, Jessica P. E.; Cui, Yongzhi; Kim, Su Young; Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Guimond, Martin] Univ Montreal, Maisonneuve Rosemont Hosp, Montreal, PQ, Canada.
[Bachovchin, William] Tufts Univ, Sackler Sch Grad Biomed Sci, Dept Biochem, Boston, MA 02111 USA.
RP Fry, TJ (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM fryt@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 52
TC 8
Z9 8
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 MAR 12
PY 2013
VL 8
IS 3
AR e58860
DI 10.1371/journal.pone.0058860
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107WV
UT WOS:000316252500050
PM 23554941
ER
PT J
AU Yang, BK
Ma, CC
Chen, ZS
Yi, WN
McNutt, MA
Wang, Y
Korteweg, C
Gu, J
AF Yang, Baokai
Ma, Changchun
Chen, Zhengshan
Yi, Weining
McNutt, Michael A.
Wang, Yun
Korteweg, Christine
Gu, Jiang
TI Correlation of Immunoglobulin G Expression and Histological Subtype and
Stage in Breast Cancer
SO PLOS ONE
LA English
DT Article
ID CHAIN CONSTANT-REGION; KAPPA-LIGHT-CHAIN; DUCTAL CARCINOMA; CELL-LINES;
JAPANESE WOMEN; RISK-FACTORS; PLASMA IGA; IN-SITU; TUMORS; PREVENTION
AB Introduction: Recently, growing evidence indicates that immunoglobulins (Igs) are not only produced by mature B lymphocytes or plasma cells, but also by various normal cells types at immune privileged sites and neoplasm, including breast cancer. However, the association of breast cancer derived IgG with genesis and development of the disease has not yet been established.
Methods: In this study we examined the expression of IgG in 186 breast cancers, 20 benign breast lesions and 30 normal breast tissues. Both immunohistochemistry with antibodies to Ig kappa (immunoglobulin G kappa light chain) and Ig gamma (immunoglobulin G heavy chain) and in situ hybridization with an antisense probe to IgG1 heavy chain constant region gene were performed. Various clinicopathological features were also analyzed.
Results: We found that IgG is specifically expressed in human breast cancer cells. Both infiltrating ductal carcinoma and infiltrating lobular carcinoma had significantly greater numbers of Ig kappa and Ig gamma positive cancer cells as compared with medullary carcinoma, carcinoma in situ, and benign lesions (all p<0.05). In addition, IgG expression was correlated with breast cancer histological subtypes (p<0.01) and AJCC stages (p<0.05), with more abundance of IgG expression in more malignant histological subtypes or in more advanced stage of the disease.
Conclusions: IgG expression in breast cancer cells is correlated with malignancy and AJCC stages of the cancers. This suggests that breast cancer derived IgG may be associated with genesis, development and prognosis of the cancer.
C1 [Yang, Baokai; Chen, Zhengshan; McNutt, Michael A.; Wang, Yun; Gu, Jiang] Peking Beijing Univ, Dept Pathol, Sch Basic Med Sci, Hlth Sci Ctr, Beijing, Peoples R China.
[Ma, Changchun; Chen, Zhengshan; Korteweg, Christine; Gu, Jiang] Shantou Univ, Guangdong Prov Key Lab Infect Dis & Mol Immunopat, Dept Pathol & Pathophysiol, Coll Med, Shantou, Peoples R China.
[Ma, Changchun] Shantou Univ, Dept Radiat Oncol, Canc Hosp, Coll Med, Shantou, Peoples R China.
[Yi, Weining] Peking Beijing Univ, Dept Epidemiol & Biostat, Sch Publ Hlth, Hlth Sci Ctr, Beijing, Peoples R China.
[Wang, Yun] NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA.
RP Gu, J (reprint author), Peking Beijing Univ, Dept Pathol, Sch Basic Med Sci, Hlth Sci Ctr, Beijing, Peoples R China.
EM jguemailbox@gmail.com
RI Chen, Zhengshan/J-7499-2014
FU Li Fu Educational Foundation; 111 project of the Ministry of Education,
China [B07001]; National Natural Science Foundation of China [81030033,
30971150]; Science and Technology Funding of Shantou [186]
FX This work was supported by the Li Fu Educational Foundation, 111 project
of the Ministry of Education, China (No. B07001), the National Natural
Science Foundation of China (Nos. 81030033 and 30971150 to J.G.) and the
Science and Technology Funding of Shantou (No. 186 to C. M.). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 43
TC 2
Z9 2
U1 0
U2 10
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 MAR 12
PY 2013
VL 8
IS 3
AR e58706
DI 10.1371/journal.pone.0058706
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107WV
UT WOS:000316252500040
PM 23554916
ER
PT J
AU Sabino, EC
Ribeiro, AL
Salemi, VMC
Oliveira, CD
Antunes, AP
Menezes, MM
Ianni, BM
Nastari, L
Fernandes, F
Patavino, GM
Sachdev, V
Capuani, L
de Almeida-Neto, C
Carrick, DM
Wright, D
Kavounis, K
Goncalez, TT
Carneiro-Proietti, AB
Custer, B
Busch, MP
Murphy, EL
AF Sabino, Ester C.
Ribeiro, Antonio L.
Salemi, Vera M. C.
Oliveira, Claudia Di Lorenzo
Antunes, Andre P.
Menezes, Marcia M.
Ianni, Barbara M.
Nastari, Luciano
Fernandes, Fabio
Patavino, Giuseppina M.
Sachdev, Vandana
Capuani, Ligia
de Almeida-Neto, Cesar
Carrick, Danielle M.
Wright, David
Kavounis, Katherine
Goncalez, Thelma T.
Carneiro-Proietti, Anna Barbara
Custer, Brian
Busch, Michael P.
Murphy, Edward L.
CA Natl Heart Lung Blood Inst
TI Ten-Year Incidence of Chagas Cardiomyopathy Among Asymptomatic
Trypanosoma cruzi-Seropositive Former Blood Donors
SO CIRCULATION
LA English
DT Article
DE blood donors; Brazil; Chagas cardiomyopathy; Chagas disease; incidence
ID HEART-DISEASE; UNITED-STATES; MORTALITY; RISK; PREDICTORS;
ECHOCARDIOGRAPHY; RECOMMENDATIONS; TRANSMISSION; MORBIDITY; INFECTION
AB Background-Very few studies have measured disease penetrance and prognostic factors of Chagas cardiomyopathy among asymptomatic Trypanosoma cruzi-infected persons.
Methods and Results-We performed a retrospective cohort study among initially healthy blood donors with an index T cruzi-seropositive donation and age-, sex-, and period-matched seronegatives in 1996 to 2002 in the Brazilian cities of Sao Paulo and Montes Claros. In 2008 to 2010, all subjects underwent medical history, physical examination, ECGs, and echocardiograms. ECG and echocardiogram results were classified by blinded core laboratories, and records with abnormal results were reviewed by a blinded panel of 3 cardiologists who adjudicated the outcome of Chagas cardiomyopathy. Associations with Chagas cardiomyopathy were tested with multivariate logistic regression. Mean follow-up time between index donation and outcome assessment was 10.5 years for the seropositives and 11.1 years for the seronegatives. Among 499 T cruzi seropositives, 120 (24%) had definite Chagas cardiomyopathy, and among 488 T cruzi seronegatives, 24 (5%) had cardiomyopathy, for an incidence difference of 1.85 per 100 person-years attributable to T cruzi infection. Of the 120 seropositives classified as having Chagas cardiomyopathy, only 31 (26%) presented with ejection fraction <50%, and only 11 (9%) were classified as New York Heart Association class II or higher. Chagas cardiomyopathy was associated (P<0.01) with male sex, a history of abnormal ECG, and the presence of an S-3 heart sound.
Conclusions-There is a substantial annual incidence of Chagas cardiomyopathy among initially asymptomatic T cruzi-seropositive blood donors, although disease was mild at diagnosis. (Circulation. 2013;127:1105-1115.)
C1 [Sabino, Ester C.] Univ Sao Paulo, Dept Infect Dis, Sao Paulo, Brazil.
[Sabino, Ester C.] Univ Sao Paulo, Inst Trop Med, Sao Paulo, Brazil.
[Ribeiro, Antonio L.] Univ Fed Minas Gerais, Hosp Clin, Belo Horizonte, MG, Brazil.
[Ribeiro, Antonio L.] Univ Fed Minas Gerais, Fac Med, Belo Horizonte, MG, Brazil.
[Salemi, Vera M. C.; Ianni, Barbara M.; Nastari, Luciano; Fernandes, Fabio] Univ Sao Paulo, Fac Med, Heart Inst InCor, Cardiomyopathy Unit, Sao Paulo, Brazil.
[Oliveira, Claudia Di Lorenzo] Univ Fed Sao Joao del Rei, Divinopolis, Brazil.
[Antunes, Andre P.; Menezes, Marcia M.] Ctr Ciencias Biol & Saude, Prontosocor De Montes Cl, MG, Brazil.
[Patavino, Giuseppina M.; Capuani, Ligia; de Almeida-Neto, Cesar] Fundacao Prosangue Hemoctr Sao Paulo, Sao Paulo, Brazil.
[Sachdev, Vandana] NHLBI, Bethesda, MD 20892 USA.
[Carrick, Danielle M.; Wright, David; Kavounis, Katherine] Westat Corp, Rockville, MD USA.
[Goncalez, Thelma T.; Custer, Brian; Busch, Michael P.; Murphy, Edward L.] Blood Syst Res Inst, San Francisco, CA USA.
[Carneiro-Proietti, Anna Barbara] Hemominas, Belo Horizonte, MG, Brazil.
[Carneiro-Proietti, Anna Barbara; Busch, Michael P.] Fac Saude & Ecol Humana, Vespasiano, Brazil.
[Murphy, Edward L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Murphy, EL (reprint author), UCSF, BSRI, 270 Masonic Ave, San Francisco, CA 94118 USA.
EM murphy@ucsf.edu
RI Fernandes, Fabio/D-5994-2012; Ribeiro, Antonio/C-2707-2009; Nastari,
Luciano/C-8528-2012; de Almeida-Neto, Cesar/O-9224-2014; Sabino,
Ester/F-7750-2010; Salemi, Vera/C-9104-2013; Ianni, Barbara/C-7689-2012;
OI Ribeiro, Antonio/0000-0002-2740-0042; Nastari,
Luciano/0000-0002-7959-3827; Sabino, Ester/0000-0003-2623-5126; Salemi,
Vera/0000-0002-7152-1810; Ianni, Barbara/0000-0002-1588-5492; Capuani,
Ligia/0000-0002-3467-6805
FU National Institutes of Health, REDS-II International Component
[HHSN-268200417175-C]; Intramural Research Program of the NHLBI; NHLBI
FX This study was supported by the NHLBI, National Institutes of Health,
REDS-II International Component (contract HHSN-268200417175-C) and by
the Intramural Research Program of the NHLBI.
NR 27
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Z9 39
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD MAR 12
PY 2013
VL 127
IS 10
BP 1105
EP +
DI 10.1161/CIRCULATIONAHA.112.123612
PG 14
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 104NH
UT WOS:000316000300010
PM 23393012
ER
PT J
AU Bailey, RL
Gahche, JJ
Miller, PE
Thomas, PR
Dwyer, JT
AF Bailey, Regan L.
Gahche, Jaime J.
Miller, Paige E.
Thomas, Paul R.
Dwyer, Johanna T.
TI Why US Adults Use Dietary Supplements
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID CARDIOVASCULAR-DISEASE; ALTERNATIVE MEDICINE; NATIONAL-HEALTH;
UNITED-STATES; CANCER; VITAMIN; WOMEN; METAANALYSIS; PREVENTION;
PATTERNS
AB Background: Dietary supplements are used by more than half of adults, although to our knowledge, the reasons motivating use have not been previously examined in US adults using nationally representative data. The purpose of this analysis was to examine motivations for dietary supplement use, characterize the types of products used for the most commonly reported motivations, and to examine the role of physicians and health care practitioners in guiding choices about dietary supplements.
Methods: Data from adults (>= 20 years; n = 11 956) were examined in the 2007-2010 National Health and Nutrition Examination Survey, a nationally representative, cross-sectional, population-based survey.
Results: The most commonly reported reasons for using supplements were to "improve" (45%) or "maintain" (33%) overall health. Women used calcium products for "bone health" (36%), whereas men were more likely to report supplement use for "heart health or to lower cholesterol" (18%). Older adults (>= 60 years) were more likely than younger individuals to report motivations related to site-specific reasons like heart, bone and joint, and eye health. Only 23% of products were used based on recommendations of a health care provider. Multivitaminmineral products were the most frequently reported type of supplement taken, followed by calcium and omega-3 or fish oil supplements. Supplement users are more likely to report very good or excellent health, have health insurance, use alcohol moderately, eschew cigarette smoking, and exercise more frequently than nonusers.
Conclusions: Supplement users reported motivations related to overall health more commonly than for supplementing nutrients from food intakes. Use of supplements was related to more favorable health and lifestyle choices. Less than a quarter of supplements used by adults were recommended by a physician or health care provider.
C1 [Bailey, Regan L.; Thomas, Paul R.; Dwyer, Johanna T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Miller, Paige E.] NCI, NIH, Bethesda, MD 20892 USA.
[Gahche, Jaime J.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
[Dwyer, Johanna T.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Dwyer, Johanna T.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Dwyer, Johanna T.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
RP Bailey, RL (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,3B01, Bethesda, MD 20892 USA.
EM baileyr@mail.nih.gov
OI Dwyer, Johanna/0000-0002-0783-1769
FU NIH, Office of Dietary Supplements
FX This work was supported by the NIH, Office of Dietary Supplements.
NR 36
TC 124
Z9 125
U1 4
U2 53
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 MAR 11
PY 2013
VL 173
IS 5
BP 355
EP 361
DI 10.1001/jamainternmed.2013.2299
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 153OY
UT WOS:000319613100007
PM 23381623
ER
PT J
AU Barthwal, MK
Anzinger, JJ
Xu, Q
Bohnacker, T
Wymann, MP
Kruth, HS
AF Barthwal, Manoj K.
Anzinger, Joshua J.
Xu, Qing
Bohnacker, Thomas
Wymann, Matthias P.
Kruth, Howard S.
TI Fluid-Phase Pinocytosis of Native Low Density Lipoprotein Promotes
Murine M-CSF Differentiated Macrophage Foam Cell Formation
SO PLOS ONE
LA English
DT Article
ID COLONY-STIMULATING FACTOR; RECEPTOR-MEDIATED ENDOCYTOSIS;
ATHEROSCLEROTIC LESIONS; APOLIPOPROTEIN-E; MICE DEFICIENT;
PHOSPHOINOSITIDE 3-KINASE; HYPERLIPIDEMIC MICE; CULTURED-CELLS; FACTOR
OP; MACROPINOCYTOSIS
AB During atherosclerosis, low-density lipoprotein (LDL)-derived cholesterol accumulates in macrophages to form foam cells. Macrophage uptake of LDL promotes foam cell formation but the mechanism mediating this process is not clear. The present study investigates the mechanism of LDL uptake for macrophage colony-stimulating factor (M-CSF)-differentiated murine bone marrow-derived macrophages. LDL receptor-null (LDLR-/-) macrophages incubated with LDL showed non-saturable accumulation of cholesterol that did not down-regulate for the 24 h examined. Incubation of LDLR-/- macrophages with increasing concentrations of I-125-LDL showed non-saturable macrophage LDL uptake. A 20-fold excess of unlabeled LDL had no effect on I-125-LDL uptake by wild-type macrophages and genetic deletion of the macrophage scavenger receptors CD36 and SRA did not affect I-125-LDL uptake, showing that LDL uptake occurred by fluid-phase pinocytosis independently of receptors. Cholesterol accumulation was inhibited approximately 50% in wild-type and LDLR-/- mice treated with LY294002 or wortmannin, inhibitors of all classes of phosphoinositide 3-kinases (PI3K). Time-lapse, phase-contrast microscopy showed that macropinocytosis, an important fluid-phase uptake pathway in macrophages, was blocked almost completely by PI3K inhibition with wortmannin. Pharmacological inhibition of the class I PI3K isoforms alpha, beta, gamma or delta did not affect macrophage LDL-derived cholesterol accumulation or macropinocytosis. Furthermore, macrophages from mice expressing kinase-dead class I PI3K beta, gamma or delta isoforms showed no decrease in cholesterol accumulation or macropinocytosis when compared with wild-type macrophages. Thus, non-class I PI3K isoforms mediated macropinocytosis in these macrophages. Further characterization of the components necessary for LDL uptake, cholesterol accumulation, and macropinocytosis identified dynamin, microtubules, actin, and vacuolar type H(+)-ATPase as contributing to uptake. However, Pak1, Rac1, and Src-family kinases, which mediate fluid-phase pinocytosis in certain other cell types, were unnecessary. In conclusion, our findings provide evidence that targeting those components mediating macrophage macropinocytosis with inhibitors may be an effective strategy to limit macrophage accumulation of LDL-derived cholesterol in arteries.
C1 [Barthwal, Manoj K.; Anzinger, Joshua J.; Xu, Qing; Kruth, Howard S.] NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA.
[Bohnacker, Thomas; Wymann, Matthias P.] Univ Basel, Dept Biomed, Basel, Switzerland.
RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM kruthh@nhlbi.nih.gov
RI Wymann, Matthias/C-3227-2008
FU Intramural Research Program, National Heart, Lung, and Blood Institute,
National Institutes of Health; Indo-US Science and Technology Forum;
International Atherosclerosis Society
FX This work was supported by the Intramural Research Program, National
Heart, Lung, and Blood Institute, National Institutes of Health. Its
contents are solely the responsibility of the authors and do not
necessarily represent the official views of the National Institutes of
Health. M. K. B. was supported by a fellowship from the Indo-US Science
and Technology Forum and received additional support from the
International Atherosclerosis Society. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 53
TC 6
Z9 6
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 MAR 11
PY 2013
VL 8
IS 3
AR e58054
DI 10.1371/journal.pone.0058054
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107WI
UT WOS:000316251100027
PM 23536783
ER
PT J
AU Polackwich, RJ
Koch, D
Arevalo, R
Miermont, AM
Jee, KJ
Lazar, J
Urbach, J
Mueller, SC
McAllister, RG
AF Polackwich, Robert J.
Koch, Daniel
Arevalo, Richard
Miermont, Anne M.
Jee, Kathleen J.
Lazar, John
Urbach, Jeffrey
Mueller, Susette C.
McAllister, Ryan G.
TI A Novel 3D Fibril Force Assay Implicates Src in Tumor Cell Force
Generation in Collagen Networks
SO PLOS ONE
LA English
DT Article
ID FAMILY KINASES; TRACTION FORCE; CANCER-CELLS; EXTRACELLULAR PROTEOLYSIS;
SIGNAL-TRANSDUCTION; MECHANICAL FORCE; FOCAL ADHESIONS; BREAST-CANCER;
LEADING-EDGE; RPTP-ALPHA
AB New insight into the biomechanics of cancer cell motility in 3D extracellular matrix (ECM) environments would significantly enhance our understanding of aggressive cancers and help identify new targets for intervention. While several methods for measuring the forces involved in cell-matrix interactions have been developed, previous to this study none have been able to measure forces in a fibrillar environment. We have developed a novel assay for simultaneously measuring cell mechanotransduction and motility in 3D fibrillar environments. The assay consists of a controlled-density fibrillar collagen gel atop a controlled-stiffness polyacrylamide (PAA) surface. Forces generated by living cells and their migration in the 3D collagen gel were measured with the 3D motion of tracer beads within the PAA layer. Here, this 3D fibril force assay is used to study the role of the invasion-associated protein kinase Src in mechanotransduction and motility. Src expression and activation are linked with proliferation, invasion, and metastasis, and have been shown to be required in 2D for invadopodia membranes to direct and mediate invasion. Breast cancer cell line MDA-MD-231 was stably transfected with GFP-tagged constitutively active Src or wild-type Src. In 3D fibrillar collagen matrices we found that, relative to wild-type Src, constitutively active Src: 1) increased the strength of cell-induced forces on the ECM, 2) did not significantly change migration speed, and 3) increased both the duration and the length, but not the number, of long membrane protrusions. Taken together, these results support the hypothesis that Src controls invasion by controlling the ability of the cell to form long lasting cellular protrusions to enable penetration through tissue barriers, in addition to its role in promoting invadopodia matrix-degrading activity.
C1 [Polackwich, Robert J.; Koch, Daniel; Arevalo, Richard; Urbach, Jeffrey; McAllister, Ryan G.] Georgetown Univ, Dept Phys, Washington, DC 20057 USA.
[Miermont, Anne M.; Jee, Kathleen J.; Lazar, John; Mueller, Susette C.; McAllister, Ryan G.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA.
[Miermont, Anne M.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP McAllister, RG (reprint author), Georgetown Univ, Dept Phys, Washington, DC 20057 USA.
EM rmca@physics.georgetown.edu
OI Urbach, Jeffrey/0000-0002-1593-520X
FU National Cancer Institute [5K25CA126836]; National Science Foundation
[DMR-0804782]; Lombardi Comprehensive Cancer Center Microscopy and
Imaging Shared Resource; U.S. Public Health Service [2P30-CA-51008, 1S10
RR15768-01, 1 S10 RR019291-01A2]; [9R01 CA112673]
FX This project was supported in part by Award Number 5K25CA126836 from the
National Cancer Institute to RM and supported in part by Award number
DMR-0804782 from the National Science Foundation. 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. This work was further supported in part by the
Lombardi Comprehensive Cancer Center Microscopy and Imaging Shared
Resource funded by U.S. Public Health Service Grants 2P30-CA-51008, 1S10
RR15768-01, and 1 S10 RR019291-01A2 and by 9R01 CA112673 to SCM. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 78
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U1 1
U2 36
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 MAR 11
PY 2013
VL 8
IS 3
AR e58138
DI 10.1371/journal.pone.0058138
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107WI
UT WOS:000316251100028
PM 23536784
ER
PT J
AU Yao, XH
Ping, YF
Liu, Y
Chen, KQ
Yoshimura, T
Liu, MY
Gong, WH
Chen, C
Niu, Q
Guo, DY
Zhang, X
Wang, JM
Bian, XW
AF Yao, Xiaohong
Ping, Yifang
Liu, Ying
Chen, Kequiang
Yoshimura, Teizo
Liu, Mingyong
Gong, Wanghua
Chen, Chong
Niu, Qin
Guo, Deyu
Zhang, Xia
Wang, Ji Ming
Bian, Xiuwu
TI Plays a Key Role in Vasculogenic Mimicry Formation, Neovascularization
and Tumor Initiation by Glioma Stem-like Cells
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; FORMYLPEPTIDE RECEPTOR FPR; BEVACIZUMAB PLUS
IRINOTECAN; CANCER-CELLS; RECURRENT GLIOBLASTOMA; PROGENITOR CELLS;
PRECURSOR CELLS; BLOOD-VESSELS; ANGIOGENESIS; IDENTIFICATION
AB Human glioblastomas (GBM) are thought to be initiated by glioma stem-like cells (GSLCs). GSLCs also participate in tumor neovascularization by transdifferentiating into vascular endothelial cells. Here, we report a critical role of GSLCs in the formation of vasculogenic mimicry (VM), which defines channels lined by tumor cells to supply nutrients to early growing tumors and tumor initiation. GSLCs preferentially expressed vascular endothelial growth factor receptor-2 (VEGFR-2) that upon activation by VEGF, mediated chemotaxis, tubule formation and increased expression of critical VM markers by GSLCs. Knockdown of VEGFR-2 in GSLCs by shRNA markedly reduced their capacity of self-renewal, forming tubules, initiating xenograft tumors, promoting vascularization and the establishment of VM. Our study demonstrates VEGFR-2 as an essential molecule to sustain the "stemness" of GSLCs, their capacity to initiate tumor vasculature, and direct initiation of tumor.
C1 [Yao, Xiaohong; Ping, Yifang; Chen, Chong; Niu, Qin; Guo, Deyu; Zhang, Xia; Bian, Xiuwu] Third Mil Med Univ, Inst Pathol, Chongqing, Peoples R China.
[Yao, Xiaohong; Ping, Yifang; Chen, Chong; Niu, Qin; Guo, Deyu; Zhang, Xia; Bian, Xiuwu] Third Mil Med Univ, Southwest Canc Ctr, Chongqing, Peoples R China.
[Yao, Xiaohong; Liu, Ying; Chen, Kequiang; Yoshimura, Teizo; Liu, Mingyong; Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Liu, Mingyong] Third Mil Med Univ, Daping Hosp, Dept Spinal Surg, Chongqing, Peoples R China.
[Gong, Wanghua] SAIC Frederick, Basic Res Program, Frederick, MD USA.
RP Wang, JM (reprint author), NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
EM wangji@mail.nih.gov; bianxiuwu@263.net
RI Zhang, Xia/B-8152-2008; Bian, Xiu-wu/D-4736-2017
OI Zhang, Xia/0000-0002-9040-1486; Bian, Xiu-wu/0000-0003-4383-0197
FU National Basic Research Program of China (973 Program) [2010CB529403];
National Natural Science Foundation of China (NSFC) [30800421,
30870965]; Natural Science Foundation Project of CQ (CSTC) [2008BB5136];
National Cancer Institute (NCI), National Institutes of Health (NIH)
[HHSN261200800001E]; NCI, NIH, United States of America
FX This project was supported in part by the National Basic Research
Program of China (973 Program, No. 2010CB529403), the National Natural
Science Foundation of China (NSFC, No. 30800421 and 30870965) and the
Natural Science Foundation Project of CQ (CSTC, 2008BB5136). This
project was also funded in part with Federal funds from the National
Cancer Institute (NCI), National Institutes of Health (NIH), under
Contract No. HHSN261200800001E and was supported in part by the
Intramural Research Program of the NCI, NIH, United States of America.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 56
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Z9 42
U1 0
U2 19
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 MAR 11
PY 2013
VL 8
IS 3
AR e57188
DI 10.1371/journal.pone.0057188
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107WI
UT WOS:000316251100009
PM 23536763
ER
PT J
AU Kotlarz, D
Zietara, N
Uzel, G
Weidemann, T
Braun, CJ
Diestelhorst, J
Krawitz, PM
Robinson, PN
Hecht, J
Puchalka, J
Gertz, EM
Schaffer, AA
Lawrence, MG
Kardava, L
Pfeifer, D
Baumann, U
Pfister, ED
Hanson, EP
Schambach, A
Jacobs, R
Kreipe, H
Moir, S
Milner, JD
Schwille, P
Mundlos, S
Klein, C
AF Kotlarz, Daniel
Zietara, Natalia
Uzel, Gulbu
Weidemann, Thomas
Braun, Christian J.
Diestelhorst, Jana
Krawitz, Peter M.
Robinson, Peter N.
Hecht, Jochen
Puchalka, Jacek
Gertz, E. Michael
Schaeffer, Alejandro A.
Lawrence, Monica G.
Kardava, Lela
Pfeifer, Dietmar
Baumann, Ulrich
Pfister, Eva-Doreen
Hanson, Eric P.
Schambach, Axel
Jacobs, Roland
Kreipe, Hans
Moir, Susan
Milner, Joshua D.
Schwille, Petra
Mundlos, Stefan
Klein, Christoph
TI Loss-of-function mutations in the IL-21 receptor gene cause a primary
immunodeficiency syndrome
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID CELL RESPONSES; WSXWS MOTIF; T-CELLS; DIFFERENTIATION; INTERLEUKIN-21;
CHAIN; DEFICIENCY; ACTIVATION; GENERATION; INFECTION
AB Primary immunodeficiencies (PIDs) represent exquisite models for studying mechanisms of human host defense. In this study, we report on two unrelated kindreds, with two patients each, who had cryptosporidial infections associated with chronic cholangitis and liver disease. Using exome and candidate gene sequencing, we identified two distinct homozygous loss-of-function mutations in the interleukin-21 receptor gene (IL21R; c.G602T, p.Arg201Leu and c.240_245delCTGCCA, p.C81_H82del). The IL-21R(Arg201Leu) mutation causes aberrant trafficking of the IL-21R to the plasma membrane, abrogates IL-21 ligand binding, and leads to defective phosphorylation of signal transducer and activator of transcription 1 (STAT1), STAT3, and STAT5. We observed impaired IL-21-induced proliferation and immunoglobulin class-switching in B cells, cytokine production in T cells, and NK cell cytotoxicity. Our study indicates that human IL-21R deficiency causes an immunodeficiency and highlights the need for early diagnosis and allogeneic hematopoietic stem cell transplantation in affected children.
C1 [Kotlarz, Daniel; Zietara, Natalia; Braun, Christian J.; Diestelhorst, Jana; Klein, Christoph] Hannover Med Sch, Dept Pediat Hematol Oncol, D-30625 Hannover, Germany.
[Baumann, Ulrich; Pfister, Eva-Doreen] Hannover Med Sch, Dept Pediat Kidney Liver & Metab Dis, D-30625 Hannover, Germany.
[Schambach, Axel] Hannover Med Sch, Dept Expt Hematol, D-30625 Hannover, Germany.
[Jacobs, Roland] Hannover Med Sch, Dept Clin Immunol & Rheumatol, D-30625 Hannover, Germany.
[Kreipe, Hans] Hannover Med Sch, Dept Pathol, D-30625 Hannover, Germany.
[Kotlarz, Daniel; Zietara, Natalia; Braun, Christian J.; Diestelhorst, Jana; Puchalka, Jacek; Klein, Christoph] Univ Munich, Dr von Hauner Childrens Hosp, Dept Pediat, D-80539 Munich, Germany.
[Uzel, Gulbu] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, Bethesda, MD USA.
[Lawrence, Monica G.; Milner, Joshua D.] NIAID, Lab Allerg Dis, Bethesda, MD USA.
[Kardava, Lela; Moir, Susan] NIAID, Lab Immunoregulat, Bethesda, MD USA.
[Hanson, Eric P.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Weidemann, Thomas; Schwille, Petra] Tech Univ Dresden, Biophys Res Grp, D-01062 Dresden, Germany.
[Krawitz, Peter M.; Robinson, Peter N.; Hecht, Jochen; Mundlos, Stefan] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
[Krawitz, Peter M.; Robinson, Peter N.; Hecht, Jochen; Mundlos, Stefan] Charite, Inst Med Genet & Human Genet, D-10117 Berlin, Germany.
[Krawitz, Peter M.; Robinson, Peter N.; Hecht, Jochen; Mundlos, Stefan] Charite, Berlin Brandenburg Ctr Regenerat Therapies BCRT, D-10117 Berlin, Germany.
[Pfeifer, Dietmar] Univ Med Ctr Freiburg, Genom Core Lab, Dept Hematol Oncol, D-79095 Freiburg, Germany.
RP Klein, C (reprint author), Hannover Med Sch, Dept Pediat Hematol Oncol, D-30625 Hannover, Germany.
EM christoph.klein@med.uni-muenchen.de
RI Krawitz, Peter/F-3142-2012;
OI Krawitz, Peter/0000-0002-3194-8625; Gertz, E.
Michael/0000-0001-8390-4387; Robinson, Peter/0000-0002-0736-9199
FU DFG [KF0250, SFB900]; BMBF (PID-NET); E-RARE; DAAD; REBIRTH [EXC62/1];
Care-for-Rare Foundation; Deutsche Jose Carreras Leukamie-Stiftung;
Intramural Research Program of the NIH; NIAID; NIAMS; NLM
FX The study is supported by grants from DFG (KF0250, SFB900,
Gottfried-Wilhelm-Leibniz Program), BMBF (PID-NET), E-RARE, DAAD,
REBIRTH (EXC62/1), Care-for-Rare Foundation, and Deutsche Jose Carreras
Leukamie-Stiftung (fellowship to D. Kotlarz). This research is supported
in part by the Intramural Research Program of the NIH, NIAID, NIAMS, and
NLM.
NR 35
TC 69
Z9 72
U1 0
U2 20
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 MAR 11
PY 2013
VL 210
IS 3
BP 433
EP 443
DI 10.1084/jem.20111229
PG 11
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 104MH
UT WOS:000315997000001
PM 23440042
ER
PT J
AU Ben-Sasson, SZ
Hogg, A
Hu-Li, J
Wingfield, P
Chen, X
Crank, M
Caucheteux, S
Ratner-Hurevich, M
Berzofsky, JA
Nir-Paz, R
Paul, WE
AF Ben-Sasson, Shlomo Z.
Hogg, Alison
Hu-Li, Jane
Wingfield, Paul
Chen, Xi
Crank, Michelle
Caucheteux, Stephane
Ratner-Hurevich, Maya
Berzofsky, Jay A.
Nir-Paz, Ran
Paul, William E.
TI IL-1 enhances expansion, effector function, tissue localization, and
memory response of antigen-specific CD8 T cells
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID ADAPTIVE IMMUNE-RESPONSES; TUMOR-NECROSIS-FACTOR; TRANSENDOTHELIAL
MIGRATION; ENDOTHELIAL-CELLS; DIFFERENTIAL EXPRESSION; ENVELOPE
GLYCOPROTEIN; CYTOKINE PRODUCTION; DENDRITIC CELLS; VACCINIA VIRUS;
CD11C(+) CELLS
AB Here, we show that interleukin-1 (IL-1) enhances antigen-driven CD8 T cell responses. When administered to recipients of OT-I T cell receptor transgenic CD8 T cells specific for an ovalbumin (OVA) peptide, IL-1 results in an increase in the numbers of wild-type but not IL1R1(-/-) OT-I cells, particularly in spleen, liver, and lung, upon immunization with OVA and lipopolysaccharide. IL-1 administration also results in an enhancement in the frequency of antigen-specific cells that are granzyme B+, have cytotoxic activity, and/ or produce interferon gamma (IFN-gamma). Cells primed in the presence of IL-1 display enhanced expression of granzyme B and increased capacity to produce IFN-gamma when rechallenged 2 mo after priming. In three in vivo models, IL-1 enhances the protective value of weak immunogens. Thus, IL-1 has a marked enhancing effect on antigen-specific CD8 T cell expansion, differentiation, migration to the periphery, and memory.
C1 [Ben-Sasson, Shlomo Z.; Hu-Li, Jane; Chen, Xi; Crank, Michelle; Caucheteux, Stephane; Paul, William E.] NIAID, Lab Immunol, Bethesda, MD USA.
[Hogg, Alison; Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Wingfield, Paul] NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA.
[Ben-Sasson, Shlomo Z.; Ratner-Hurevich, Maya] Hebrew Univ Jerusalem, Lautenberg Ctr Tumor Immunol, Hadassah Med Ctr, IL-91120 Jerusalem, Israel.
[Nir-Paz, Ran] Hebrew Univ Jerusalem, Dept Clin Microbiol & Infect Dis, Hadassah Med Ctr, IL-91120 Jerusalem, Israel.
RP Paul, WE (reprint author), NIAID, Lab Immunol, Bethesda, MD USA.
EM wpaul@niaid.nih.gov
OI Nir-Paz, Ran/0000-0002-1567-2550
FU Intramural Research Program of the National Institute for Allergy and
Infectious Disease; National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute for Allergy and Infectious Disease, National
Institutes of Health.
NR 48
TC 36
Z9 38
U1 0
U2 18
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 MAR 11
PY 2013
VL 210
IS 3
BP 491
EP 502
DI 10.1084/jem.20122006
PG 12
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 104MH
UT WOS:000315997000006
PM 23460726
ER
PT J
AU Dai, L
Lidie, KB
Chen, Q
Adelsberger, JW
Zheng, X
Huang, DW
Yang, J
Lempicki, RA
Rehman, T
Dewar, RL
Wang, YM
Hornung, RL
Canizales, KA
Lockett, SJ
Lane, HC
Imamichi, T
AF Dai, Lue
Lidie, Kristy B.
Chen, Qian
Adelsberger, Joseph W.
Zheng, Xin
Huang, DaWei
Yang, Jun
Lempicki, Richard A.
Rehman, Tauseef
Dewar, Robin L.
Wang, Yanmei
Hornung, Ronald L.
Canizales, Kelsey A.
Lockett, Stephen J.
Lane, H. Clifford
Imamichi, Tomozumi
TI IL-27 inhibits HIV-1 infection in human macrophages by down-regulating
host factor SPTBN1 during monocyte to macrophage differentiation
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL
THERAPY; REVERSE TRANSCRIPTION; MONONUCLEAR PHAGOCYTES; SAMHD1
RESTRICTS; REPLICATION FITNESS; DRUG-RESISTANCE; IN-VITRO; EXPRESSION
AB The susceptibility of macrophages to HIV-1 infection is modulated during monocyte differentiation. IL-27 is an anti-HIV cytokine that also modulates monocyte activation. In this study, we present new evidence that IL-27 promotes monocyte differentiation into macrophages that are nonpermissive for HIV-1 infection. Although IL-27 treatment does not affect expression of macrophage differentiation markers or macrophage biological functions, it confers HIV resistance by down-regulating spectrin beta nonerythrocyte 1 (SPTBN1), a required host factor for HIV-1 infection. IL-27 down-regulates SPTBN1 through a TAK-1-mediated MAPK signaling pathway. Knockdown of SPTBN1 strongly inhibits HIV-1 infection of macrophages; conversely, overexpression of SPTBN1 markedly increases HIV susceptibility of IL-27-treated macrophages. Moreover, we demonstrate that SPTBN1 associates with HIV-1 gag proteins. Collectively, our results underscore the ability of IL-27 to protect macrophages from HIV-1 infection by down-regulating SPTBN1, thus indicating that SPTBN1 is an important host target to reduce HIV-1 replication in one major element of the viral reservoir.
C1 [Dai, Lue; Lidie, Kristy B.; Chen, Qian; Adelsberger, Joseph W.; Zheng, Xin; Huang, DaWei; Yang, Jun; Lempicki, Richard A.; Rehman, Tauseef; Dewar, Robin L.; Wang, Yanmei; Hornung, Ronald L.; Canizales, Kelsey A.; Imamichi, Tomozumi] Sci Applicat Int Corp Frederick Inc, Frederick Natl Lab Canc Res, Appl & Dev Directorate, Ft Detrick, MD 21702 USA.
[Lockett, Stephen J.] Sci Applicat Int Corp Frederick Inc, Frederick Natl Lab Canc Res, Adv Technol Program Directorate, Ft Detrick, MD 21702 USA.
[Lane, H. Clifford] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Imamichi, T (reprint author), Sci Applicat Int Corp Frederick Inc, Frederick Natl Lab Canc Res, Appl & Dev Directorate, Ft Detrick, MD 21702 USA.
EM timamichi@mail.nih.gov
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
FU NCI, NIH [HHSN261200800001E]; NIAID
FX This project has been funded in whole or in part with federal funds from
the NCI, NIH, 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 NIAID.
NR 83
TC 15
Z9 16
U1 0
U2 17
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 MAR 11
PY 2013
VL 210
IS 3
BP 517
EP 534
DI 10.1084/jem.20120572
PG 18
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 104MH
UT WOS:000315997000008
PM 23460728
ER
PT J
AU Ramos-Alvarez, I
Martin-Duce, A
Moreno-Villegas, Z
Sanz, R
Aparicio, C
Portal-Nunez, S
Mantey, SA
Jensen, RT
Gonzalez, N
AF Ramos-Alvarez, Irene
Martin-Duce, Antonio
Moreno-Villegas, Zaida
Sanz, Raul
Aparicio, Cesar
Portal-Nunez, Sergio
Mantey, Samuel A.
Jensen, Robert T.
Gonzalez, Nieves
TI Bombesin receptor subtype-3 (BRS-3), a novel candidate as therapeutic
molecular target in obesity and diabetes
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Article
DE BRS-3; Human-muscle; GLUT-4; Glucose-metabolism; Diabetes; Obesity
ID RAT SKELETAL-MUSCLE; GLUCAGON-LIKE PEPTIDE-1; HUMAN ORPHAN RECEPTOR;
GLUCOSE-TRANSPORT; GENE-EXPRESSION; HIGH-AFFINITY; GLP-1; INSULIN;
METABOLISM; AGONIST
AB BRS-3 KO-mice developed obesity and unbalanced glucose metabolism, suggesting an important role of BRS-3 receptor in glucose homeostasis. We explored BRS-3 expression in skeletal muscle from normal, obese or type-2 diabetic (T2D) patients, and the effect of [D-Phe(6), beta-Ala(11), Phe(13), Nle(14)]bombesin(6-14) - BRS-3-agonist-peptide (BRS-3-AP) - on glucose-related effects, before or after BRS-3 gene silencing. In muscle tissue and primary cultured myocytes from altered metabolic states, BRS-3 gene/protein expressions were down-regulated. In normal, obese and T2D cells: A) BRS-3-AP as insulin enhanced BRS-3 and GLUT-4 mRNA/protein levels; improving glucotransporter translocation to plasma membrane, and B) BRS-3-AP caused a concentration-related-stimulation of glucose transport, being obese and T2D myocytes more sensitive to the ligand than normal. Wortmannin and PD98059, but not rapamycin, abolished the stimulatory action of BRS-3-AP on glucose transport. BRS-3 plays an important role in glucose metabolism, and could be use as a molecular target, and/or its ligand, as a therapeutic agent for obesity and diabetes treatments. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Ramos-Alvarez, Irene; Moreno-Villegas, Zaida; Gonzalez, Nieves] IIS Fdn Jimenez Diaz, Dept Metab Nutr & Hormonas, Madrid 28040, Spain.
[Ramos-Alvarez, Irene; Gonzalez, Nieves] CIBERDEM, Madrid, Spain.
[Martin-Duce, Antonio] Univ Alcala de Henares, Dept Nursery, Surg Unit, Madrid, Spain.
[Sanz, Raul] IIS Fdn Jimenez Diaz, Dept Neurol, Madrid 28040, Spain.
[Aparicio, Cesar] Fdn Jimenez Diaz, Dept Vasc Surg, Madrid, Spain.
[Portal-Nunez, Sergio] IIS Fdn Jimenez Diaz, RETICEF, Dept Bone & Mineral Metab, Madrid 28040, Spain.
[Mantey, Samuel A.; Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA.
RP Gonzalez, N (reprint author), IIS Fdn Jimenez Diaz, Dept Metab Nutr & Hormonas, Avda Reyes Catolicos 2, Madrid 28040, Spain.
EM ngonzalezg@fjd.es
RI Portal-Nunez, Sergio/L-7391-2014; Gonzalez, Nieves/N-2199-2014
OI Portal-Nunez, Sergio/0000-0003-0659-1545; Gonzalez,
Nieves/0000-0002-1551-2872
FU Instituto de Salud CarlosIII [CP08/00158]; Fundacion Eugenio Rodriguez
Pascual, Spain [12224/001]; RETICEF [RD06/0013/1002]
FX This study was supported by a grant from the Instituto de Salud
CarlosIII (CP08/00158), (ENDODIAB, CIBERDEM) and Fundacion Eugenio
Rodriguez Pascual (12224/001), Spain. I.R.A. and Z.M.V. are Research
Fellow from the Fundacion Conchita Rabago de Jimenez Diaz; S.P.N. is
recipient of a research contract from RETICEF (RD06/0013/1002). The
authors declare that there is not conflict of interest that would
prejudice the impartiality of the reported research. We thank Estrella
Martin-Crespo (Dpt. of Metabolism, Nutrition and Hormones, IIS-Fundacion
Jimenez Diaz) for excellent technical assistance and Felicidad Lopez
(Dpt. of Surgery, Fundacion Jimenez Diaz) for outstanding
sample-coordination.
NR 32
TC 6
Z9 7
U1 0
U2 14
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD MAR 10
PY 2013
VL 367
IS 1-2
BP 109
EP 115
DI 10.1016/j.mce.2012.12.025
PG 7
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 099HH
UT WOS:000315611600012
PM 23291341
ER
PT J
AU Bissler, JJ
Kingswood, JC
Radzikowska, E
Zonnenberg, BA
Frost, M
Belousova, E
Sauter, M
Nonomura, N
Brakemeier, S
de Vries, PJ
Whittemore, VH
Chen, D
Sahmoud, T
Shah, G
Lincy, J
Lebwohl, D
Budde, K
AF Bissler, John J.
Kingswood, J. Christopher
Radzikowska, Elzbieta
Zonnenberg, Bernard A.
Frost, Michael
Belousova, Elena
Sauter, Matthias
Nonomura, Norio
Brakemeier, Susanne
de Vries, Petrus J.
Whittemore, Vicky H.
Chen, David
Sahmoud, Tarek
Shah, Gaurav
Lincy, Jeremie
Lebwohl, David
Budde, Klemens
TI Everolimus for angiomyolipoma associated with tuberous sclerosis complex
or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre,
randomised, double-blind, placebo-controlled trial
SO LANCET
LA English
DT Article
ID T-CELL LYMPHOMA; RENAL ANGIOMYOLIPOMATA; CONSENSUS CONFERENCE;
CLINICAL-TRIAL; SIROLIMUS; DISEASE; EFFICACY; THERAPY; PHASE-2; WOMEN
AB Background Angiomyolipomas are slow-growing tumours associated with constitutive activation of mammalian target of rapamycin (mTOR), and are common in patients with tuberous sclerosis complex and sporadic lymphangioleiomyomatosis. The insidious growth of these tumours predisposes patients to serious complications including retroperitoneal haemorrhage and impaired renal function. Everolimus, a rapamycin derivative, inhibits the mTOR pathway by acting on the mTOR complex 1. We compared the angiomyolipoma response rate on everolimus with placebo in patients with tuberous sclerosis or sporadic lymphanioleiomyomatosis-associated angiomyolipomata.
Methods In this double-blind, placebo-controlled, phase 3 trial, patients aged 18 years or older with at least one angiomyolipoma 3 cm or larger in its longest diameter (defined by radiological assessment) and a definite diagnosis of tuberous sclerosis or sporadic lymphangioleiomyomatosis were randomly assigned, in a 2: 1 fashion with the use of an interactive web response system, to receive oral everolimus 10 mg per day or placebo. The primary efficacy endpoint was the proportion of patients with confirmed angiomyolipoma response of at least a 50% reduction in total volume of target angiomyolipomas relative to baseline. This study is registered with ClinicalTrials.gov number NCT00790400.
Results 118 patients (median age 31.0 years; IQR 18.0-61.0) from 24 centres in 11 countries were randomly assigned to receive everolimus (n=79) or placebo (n=39). At the data cutoff, double-blind treatment was ongoing for 98 patients; two main reasons for discontination were disease progression (nine placebo patients) followed by adverse events (two everolimus patients; four placebo patients). The angiomyolipoma response rate was 42% (33 of 79 [95% CI 31-53%]) for everolimus and 0% (0 of 39 [0-9%]) for placebo (response rate difference 42% [24-58%]; one-sided Cochran-Mantel-Haenszel test p<0.0001). The most common adverse events in the everolimus and placebo groups were stomatitis (48% [38 of 79], 8% [3 of 39], respectively), nasopharyngitis (24% [19 of 79] and 31% [12 of 39]), and acne-like skin lesions (22% [17 of 79] and 5% [2 of 39]).
Interpretation Everolimus reduced angiomyolipoma volume with an acceptable safety profi le, suggesting it could be a potential treatment for angiomyolipomas associated with tuberous sclerosis.
C1 [Bissler, John J.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Kingswood, J. Christopher] Royal Sussex Cty Hosp, Brighton BN2 5BE, E Sussex, England.
[Radzikowska, Elzbieta] Natl TB & Lung Dis Res Inst, Warsaw, Poland.
[Zonnenberg, Bernard A.] Univ Med Ctr, Utrecht, Netherlands.
[Frost, Michael] Minnesota Epilepsy Grp, St Paul, MN USA.
[Belousova, Elena] Moscow Res Inst Pediat & Pediat Surg, Moscow, Russia.
[Sauter, Matthias] Klinikum Univ Munchen, Med Klin & Poliklin 4, Munich, Germany.
[Nonomura, Norio] Osaka Univ Hosp, Osaka 553, Japan.
[Brakemeier, Susanne; Budde, Klemens] Charite, D-13353 Berlin, Germany.
[de Vries, Petrus J.] Univ Cape Town, Div Child & Adolescent Psychiat, ZA-7700 Rondebosch, South Africa.
[Whittemore, Vicky H.] NINDS, NIH, Bethesda, MD 20892 USA.
[Chen, David; Sahmoud, Tarek; Shah, Gaurav; Lebwohl, David] Novartis Pharmaceut, Florham Pk, NJ USA.
[Lincy, Jeremie] Novartis Pharmaceut, Basel, Switzerland.
RP Bissler, JJ (reprint author), Cincinnati Childrens Hosp Med Ctr, 240 Albert Sabin Way, Cincinnati, OH 45229 USA.
EM john.bissler@cchmc.org
RI Chiang, Vincent, Ming-Hsien/D-4312-2016;
OI Chiang, Vincent, Ming-Hsien/0000-0002-2029-7863; Belousova, Elena
Dmitrievna/0000-0003-3594-6974
FU Novartis Pharmaceuticals; Novartis
FX Funding Novartis Pharmaceuticals.; DC, TS, GS, JL, and DL are employees
of Novartis. DC, GS, and DL own Novartis stock. DL has Novartis stock
options. JJB, JCK, ER, BAZ, MF, EB, MS, PJdV, and KB are Novartis
consultants (including advisory boards), and have had travel paid,
research funded, or speaker honoraria/speakers bureau by or for
Novartis. MF is a member of speakers bureaus and advisory boards for
Lundbeck and UCB. NN, SB, and VHW declare that they have no conflicts of
interest.
NR 30
TC 222
Z9 239
U1 2
U2 14
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 MAR 9
PY 2013
VL 381
IS 9869
BP 817
EP 824
DI 10.1016/S0140-6736(12)61767-X
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 105IL
UT WOS:000316060600031
PM 23312829
ER
PT J
AU Carrington, LB
Armijos, MV
Lambrechts, L
Barker, CM
Scott, TW
AF Carrington, Lauren B.
Armijos, M. Veronica
Lambrechts, Louis
Barker, Christopher M.
Scott, Thomas W.
TI Effects of Fluctuating Daily Temperatures at Critical Thermal Extremes
on Aedes aegypti Life-History Traits
SO PLOS ONE
LA English
DT Article
ID DENGUE VIRUS TRANSMISSION; CLIMATE-CHANGE; CULICIDAE; DIPTERA;
MOSQUITOS; SURVIVAL; VECTOR; AUSTRALIA; MICROCLIMATE; CALIFORNIA
AB Background: The effect of temperature on insect biology is well understood under constant temperature conditions, but less so under more natural, fluctuating conditions. A fluctuating temperature profile around a mean of 26 degrees C can alter Aedes aegypti vector competence for dengue viruses as well as numerous life-history traits, however, the effect of fluctuations on mosquitoes at critical thermal limits is unknown.
Methodology/Principal Findings: We investigated the effects of large and small daily temperature fluctuations at low (16 degrees C) and high (35-37 degrees C) mean temperatures, after we identified these temperatures as being thresholds for immature development and/or adult reproduction under constant temperature conditions. We found that temperature effects on larval development time, larval survival and adult reproduction depend on the combination of mean temperature and magnitude of fluctuations. Importantly, observed degree-day estimates for mosquito development under fluctuating temperature profiles depart significantly (around 10-20%) from that predicted by constant temperatures of the same mean. At low mean temperatures, fluctuations reduce the thermal energy required to reach pupation relative to constant temperature, whereas at high mean temperatures additional thermal energy is required to complete development. A stage-structured model based on these empirical data predicts that fluctuations can significantly affect the intrinsic growth rate of mosquito populations.
Conclusions/Significance: Our results indicate that by using constant temperatures, one could under- or over-estimate values for numerous life-history traits compared to more natural field conditions dependent upon the mean temperature. This complexity may in turn reduce the accuracy of population dynamics modeling and downstream applications for mosquito surveillance and disease prevention.
C1 [Carrington, Lauren B.; Armijos, M. Veronica; Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
[Carrington, Lauren B.; Armijos, M. Veronica; Barker, Christopher M.; Scott, Thomas W.] Univ Calif Davis, Ctr Vectorborne Dis, Davis, CA 95616 USA.
[Lambrechts, Louis] Inst Pasteur, CNRS URA 3012, Paris, France.
[Barker, Christopher M.] Univ Calif Davis, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA.
[Barker, Christopher M.; Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Carrington, LB (reprint author), Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
EM lbcarrington@gmail.com
RI Lambrechts, Louis/A-2057-2010;
OI Lambrechts, Louis/0000-0001-5958-2138; Carrington, Lauren
Bree/0000-0001-9273-7912
FU Ecology of Infectious Disease program of the National Science Foundation
[EF-0914384]; CDC, Climate Change: Environmental Impact on Human Health
[U01 EH000418]
FX The work was funded by grant EF-0914384 from the Ecology of Infectious
Disease program of the National Science Foundation. CMB also
acknowledges financial support from grant U01 EH000418 from CDC, Climate
Change: Environmental Impact on Human Health. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 28
TC 33
Z9 36
U1 1
U2 35
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 MAR 8
PY 2013
VL 8
IS 3
AR e58824
DI 10.1371/journal.pone.0058824
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 140TZ
UT WOS:000318679900094
PM 23520534
ER
PT J
AU Brenner, AV
Neta, G
Sturgis, EM
Pfeiffer, RM
Hutchinson, A
Yeager, M
Xu, L
Zhou, C
Wheeler, W
Tucker, MA
Chanock, SJ
Sigurdson, AJ
AF Brenner, Alina V.
Neta, Gila
Sturgis, Erich M.
Pfeiffer, Ruth M.
Hutchinson, Amy
Yeager, Meredith
Xu, Li
Zhou, Cindy
Wheeler, William
Tucker, Margaret A.
Chanock, Stephen J.
Sigurdson, Alice J.
TI Common Single Nucleotide Polymorphisms in Genes Related to Immune
Function and Risk of Papillary Thyroid Cancer
SO PLOS ONE
LA English
DT Article
ID PROTEIN-C INHIBITOR; US RADIOLOGIC TECHNOLOGISTS; LINKAGE
DISEQUILIBRIUM; AUTOIMMUNE-DISEASE; FAMILY-HISTORY; UNITED-STATES;
CARCINOMA; INFLAMMATION; ASSOCIATION; RADIATION
AB Accumulating evidence suggests that alterations in immune function may be important in the etiology of papillary thyroid cancer (PTC). To identify genetic markers in immune-related pathways, we evaluated 3,985 tag single nucleotide polymorphisms (SNPs) in 230 candidate gene regions (adhesion-extravasation-migration, arachidonic acid metabolism/eicosanoid signaling, complement and coagulation cascade, cytokine signaling, innate pathogen detection and antimicrobials, leukocyte signaling, TNF/NF-kappa B pathway or other) in a case-control study of 344 PTC cases and 452 controls. We used logistic regression models to estimate odds ratios (OR) and calculate one degree of freedom P values of linear trend (PSNP-trend) for the association between genotype (common homozygous, heterozygous, variant homozygous) and risk of PTC. To correct for multiple comparisons, we applied the false discovery rate method (FDR). Gene region-and pathway-level associations (P-Region and P-Pathway) were assessed by combining individual PSNP-trend values using the adaptive rank truncated product method. Two SNPs (rs6115, rs6112) in the SERPINA5 gene were significantly associated with risk of PTC (PSNP-FDR/PSNP-trend = 0.02/6x10(-6) and PSNP-FDR/PSNP-trend = 0.04/2x10(-5), respectively). These associations were independent of a history of autoimmune thyroiditis (OR = 6.4; 95% confidence interval: 3.0-13.4). At the gene region level, SERPINA5 was suggestively associated with risk of PTC (PRegion-FDR/P-Region = 0.07/0.0003). Overall, the complement and coagulation cascade pathway was the most significant pathway (PPathway = 0.02) associated with PTC risk largely due to the strong effect of SERPINA5. Our results require replication but suggest that the SERPINA5 gene, which codes for the protein C inhibitor involved in many biological processes including inflammation, may be a new susceptibility locus for PTC.
C1 [Brenner, Alina V.; Neta, Gila; Sigurdson, Alice J.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA.
[Sturgis, Erich M.; Xu, Li] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA.
[Hutchinson, Amy; Yeager, Meredith] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Zhou, Cindy] George Washington Univ, Dept Epidemiol & Biostat, Washington, DC USA.
[Wheeler, William] Informat Management Syst, Silver Spring, MD USA.
[Tucker, Margaret A.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA.
[Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Gaithersburg, MD USA.
RP Brenner, AV (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA.
EM brennera@mail.nih.gov
RI Xu, Li/B-9535-2012; Tucker, Margaret/B-4297-2015; Zhou, Cindy
/H-2165-2015
OI Zhou, Cindy /0000-0003-4814-4305
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health;
federal funds from the National Cancer Institute, National Institutes of
Health [HHSN261200800001E]; American Thyroid Association
FX This project was supported in part by the Intramural Research Program of
the Division of Cancer Epidemiology and Genetics, National Cancer
Institute, National Institutes of Health, by federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
No. HHSN261200800001E, and by a grant from the American Thyroid
Association (PI: E. M. Sturgis). 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. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 42
TC 13
Z9 13
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 MAR 8
PY 2013
VL 8
IS 3
AR e57243
DI 10.1371/journal.pone.0057243
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 140TZ
UT WOS:000318679900023
PM 23520464
ER
PT J
AU Lizunov, VA
Stenkula, K
Troy, A
Cushman, SW
Zimmerberg, J
AF Lizunov, Vladimir A.
Stenkula, Karin
Troy, Aaron
Cushman, Samuel W.
Zimmerberg, Joshua
TI Insulin Regulates Glut4 Confinement in Plasma Membrane Clusters in
Adipose Cells
SO PLOS ONE
LA English
DT Article
ID GLUCOSE-TRANSPORT; ANCHORED PROTEINS; LIPID RAFTS; TRANSLOCATION;
VESICLES; FUSION; RAT; TRAFFICKING; MICROSCOPY; DIFFUSION
AB Insulin-stimulated delivery of glucose transporter-4 (GLUT4) to the plasma membrane (PM) is the hallmark of glucose metabolism. In this study we examined insulin's effects on GLUT4 organization in PM of adipose cells by direct microscopic observation of single monomers tagged with photoswitchable fluorescent protein. In the basal state, after exocytotic delivery only a fraction of GLUT4 is dispersed into the PM as monomers, while most of the GLUT4 stays at the site of fusion and forms elongated clusters (60-240 nm). GLUT4 monomers outside clusters diffuse freely and do not aggregate with other monomers. In contrast, GLUT4 molecule collision with an existing cluster can lead to immediate confinement and association with that cluster. Insulin has three effects: it shifts the fraction of dispersed GLUT4 upon delivery, it augments the dissociation of GLUT4 monomers from clusters similar to 3-fold and it decreases the rate of endocytic uptake. All together these three effects of insulin shift most of the PM GLUT4 from clustered to dispersed states. GLUT4 confinement in clusters represents a novel kinetic mechanism for insulin regulation of glucose homeostasis.
C1 [Lizunov, Vladimir A.; Troy, Aaron; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
[Stenkula, Karin; Cushman, Samuel W.] NIDDKD, Expt Diabet Metab & Nutr Sect, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
RP Zimmerberg, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
EM joshz@mail.nih.gov
FU Intramural Research Programs of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD); National
Institute of Diabetes and Digestive and Kidney Diseases
FX This work was funded by the Intramural Research Programs of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD) and the National Institute of Diabetes and Digestive and Kidney
Diseases. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 44
TC 8
Z9 8
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 MAR 8
PY 2013
VL 8
IS 3
AR e57559
DI 10.1371/journal.pone.0057559
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 140TZ
UT WOS:000318679900031
PM 23520472
ER
PT J
AU Tran, DT
Ten Hagen, KG
AF Tran, Duy T.
Ten Hagen, Kelly G.
TI Mucin-type O-Glycosylation during Development
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Review
ID POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; FAMILIAL TUMORAL
CALCINOSIS; CORONARY-ARTERY-DISEASE; UDP-GALNAC;
DROSOPHILA-MELANOGASTER; MICE LACKING; CORE-1
BETA-1,3-GALACTOSYLTRANSFERASE; CAENORHABDITIS-ELEGANS; MOLECULAR
CHAPERONE; NERVOUS-SYSTEM
AB Mucin-type O-glycosylation is an evolutionarily conserved protein modification present on membrane-bound and secreted proteins. Aberrations in O-glycosylation are responsible for certain human diseases and are associated with disease risk factors. Recent studies have demonstrated essential roles for mucin-type O-glycosylation in protein secretion, stability, processing, and function. Here, we summarize our current understanding of the diverse roles of mucin-type O-glycosylation during eukaryotic development. Appreciating how this conserved modification operates in developmental processes will provide insight into its roles in human disease and disease susceptibilities.
C1 [Tran, Duy T.; Ten Hagen, Kelly G.] NIDCR, Dev Glycobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Ten Hagen, KG (reprint author), NIDCR, Dev Glycobiol Sect, NIH, Bethesda, MD 20892 USA.
EM kelly.tenhagen@nih.gov
FU Intramural Research Program of the NIDCR, National Institutes of Health
FX This work was supported by the Intramural Research Program of the NIDCR,
National Institutes of Health. This is the third article in the Thematic
Minireview Series on Glycobiology and Extracellular Matrices: Glycan
Functions Pervade Biology at All Levels.
NR 76
TC 49
Z9 50
U1 1
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 MAR 8
PY 2013
VL 288
IS 10
BP 6921
EP 6929
DI 10.1074/jbc.R112.418558
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 104NY
UT WOS:000316002400014
PM 23329828
ER
PT J
AU Meitzler, JL
Hinde, S
Banfi, B
Nauseef, WM
de Montellano, PRO
AF Meitzler, Jennifer L.
Hinde, Sara
Banfi, Botond
Nauseef, William M.
de Montellano, Paul R. Ortiz
TI Conserved Cysteine Residues Provide a Protein-Protein Interaction
Surface in Dual Oxidase (DUOX) Proteins
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HUMAN MYELOPEROXIDASE; ANGSTROM RESOLUTION; FUNCTIONAL-ANALYSIS;
CATALYTIC-ACTIVITY; CONGENITAL GOITER; CRYSTAL-STRUCTURE; STRUCTURAL
BASIS; PLASMA-MEMBRANE; NADPH OXIDASES; DOMAIN
AB Intramolecular disulfide bond formation is promoted in oxidizing extracellular and endoplasmic reticulum compartments and often contributes to protein stability and function. DUOX1 and DUOX2 are distinguished from other members of the NOX protein family by the presence of a unique extracellular N-terminal region. These peroxidase-like domains lack the conserved cysteines that confer structural stability to mammalian peroxidases. Sequence-based structure predictions suggest that the thiol groups present are solvent-exposed on a single protein surface and are too distant to support intramolecular disulfide bond formation. To investigate the role of these thiol residues, we introduced four individual cysteine to glycine mutations in the peroxidase-like domains of both human DUOXs and purified the recombinant proteins. The mutations caused little change in the stabilities of the monomeric proteins, supporting the hypothesis that the thiol residues are solvent-exposed and not involved in disulfide bonds that are critical for structural integrity. However, the ability of the isolated hDUOX1 peroxidase-like domain to dimerize was altered, suggesting a role for these cysteines in protein-protein interactions that could facilitate homodimerization of the peroxidase-like domain or, in the full-length protein, heterodimeric interactions with a maturation protein. When full-length hDUOX1 was expressed in HEK293 cells, the mutations resulted in decreased H2O2 production that correlated with a decreased amount of the enzyme localized to the membrane surface rather than with a loss of activity or with a failure to synthesize the mutant proteins. These results support a role for the cysteine residues in intermolecular disulfide bond formation with the DUOX maturation factor DUOXA1.
C1 [Meitzler, Jennifer L.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hinde, Sara; Banfi, Botond; Nauseef, William M.] Univ Iowa, Inflammat Program, Dept Med, Iowa City, IA 52240 USA.
[Banfi, Botond] Univ Iowa, Dept Anat & Cell Biol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52240 USA.
[Banfi, Botond] Vet Adm Med Ctr, Iowa City, IA 52240 USA.
[de Montellano, Paul R. Ortiz] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
RP de Montellano, PRO (reprint author), Univ Calif San Francisco, Genentech Hall GH N572D,600 16th St, San Francisco, CA 94158 USA.
EM ortiz@cgl.ucsf.edu
FU National Institutes of Health [DK 30297, HL 090830, AI 70958, AI
044642]; National Center for Research Resources Grant [P41RR001614]
FX This work was supported by National Institutes of Health Grants DK 30297
(to P. R. O. M.), HL 090830 (to B. B.), and AI 70958 and AI 044642 (to
W. M. N.). This work was also supported by the resources and use of
facilities at the Iowa City Department of Veterans Affairs Medical
Center, Iowa City, IA (to W. M. N.).; We thank Karine Reiter and the
Narum laboratory for the use of their JASCO J-815 spectropolarimeter.
Mass spectrometric proteomic analyses were carried out by Bio-Organic
Bio-medical Mass Spectrometry Resource at the University of California
(director, A. L. Burlingame) supported by National Center for Research
Resources Grant P41RR001614.
NR 42
TC 12
Z9 12
U1 0
U2 9
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 MAR 8
PY 2013
VL 288
IS 10
BP 7147
EP 7157
DI 10.1074/jbc.M112.414797
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 104NY
UT WOS:000316002400036
PM 23362256
ER
PT J
AU Hubbard, BP
Gomes, AP
Dai, H
Li, J
Case, AW
Considine, T
Riera, TV
Lee, JE
Yen, ES
Lamming, DW
Pentelute, BL
Schuman, ER
Stevens, LA
Ling, AJY
Armour, SM
Michan, S
Zhao, HZ
Jiang, Y
Sweitzer, SM
Blum, CA
Disch, JS
Ng, PY
Howitz, KT
Rolo, AP
Hamuro, Y
Moss, J
Perni, RB
Ellis, JL
Vlasuk, GP
Sinclair, DA
AF Hubbard, Basil P.
Gomes, Ana P.
Dai, Han
Li, Jun
Case, April W.
Considine, Thomas
Riera, Thomas V.
Lee, Jessica E.
Yen, Sook E.
Lamming, Dudley W.
Pentelute, Bradley L.
Schuman, Eli R.
Stevens, Linda A.
Ling, Alvin J. Y.
Armour, Sean M.
Michan, Shaday
Zhao, Huizhen
Jiang, Yong
Sweitzer, Sharon M.
Blum, Charles A.
Disch, Jeremy S.
Ng, Pui Yee
Howitz, Konrad T.
Rolo, Anabela P.
Hamuro, Yoshitomo
Moss, Joel
Perni, Robert B.
Ellis, James L.
Vlasuk, George P.
Sinclair, David A.
TI Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric
Activators
SO SCIENCE
LA English
DT Article
ID SMALL-MOLECULE ACTIVATORS; MITOCHONDRIAL-FUNCTION; DEACETYLASE ACTIVITY;
RESVERATROL; SIRTUINS; SURVIVAL; TRANSCRIPTION; ACETYLATION; MODULATION;
SRT1720
AB A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists around the mechanism of sirtuin-activating compounds (STACs). We found that specific hydrophobic motifs found in SIRT1 substrates such as PGC-1 alpha and FOXO3a facilitate SIRT1 activation by STACs. A single amino acid in SIRT1, Glu(230), located in a structured N-terminal domain, was critical for activation by all previously reported STAC scaffolds and a new class of chemically distinct activators. In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs.
C1 [Hubbard, Basil P.; Gomes, Ana P.; Li, Jun; Lamming, Dudley W.; Ling, Alvin J. Y.; Armour, Sean M.; Michan, Shaday; Sinclair, David A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Gomes, Ana P.; Rolo, Anabela P.] Univ Coimbra, Dept Life Sci, Ctr Neurosci & Cell Biol, P-3004517 Coimbra, Portugal.
[Dai, Han; Case, April W.; Considine, Thomas; Riera, Thomas V.; Schuman, Eli R.; Blum, Charles A.; Disch, Jeremy S.; Ng, Pui Yee; Perni, Robert B.; Ellis, James L.; Vlasuk, George P.] Sirtris, Cambridge, MA 02139 USA.
[Lee, Jessica E.; Yen, Sook E.; Hamuro, Yoshitomo] ExSAR Corp, Monmouth Jct, NJ 08852 USA.
[Pentelute, Bradley L.] MIT, Dept Chem, Cambridge, MA 02139 USA.
[Stevens, Linda A.; Moss, Joel] NHLBI, NIH, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA.
[Zhao, Huizhen; Jiang, Yong; Sweitzer, Sharon M.] GlaxoSmithKline, Collegeville, PA 19426 USA.
[Howitz, Konrad T.] BIOMOL Res Labs Inc, Plymouth Meeting, PA 19462 USA.
[Rolo, Anabela P.] Univ Aveiro, Dept Biol, P-3810193 Aveiro, Portugal.
[Sinclair, David A.] Univ New S Wales, Dept Pharmacol, Sydney, NSW 2052, Australia.
RP Sinclair, DA (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM david_sinclair@hms.harvard.edu
RI Li, Jun/B-8055-2014;
OI Lee, Jessica/0000-0002-8567-1633; Sinclair, David/0000-0002-9936-436X;
Rolo, Anabela/0000-0003-3535-9630; Lamming, Dudley/0000-0002-0079-4467
FU Glenn Foundation for Medical Research; Ellison Medical Foundation;
Juvenile Diabetes Research Foundation; United Mitochondrial Disease
Foundation; NIH; NIAID; NSERC fellowship; Portuguese Science and
Technology Foundation; Intramural Research Program; NIH/NHLBI
FX Supported by the Glenn Foundation for Medical Research, the Ellison
Medical Foundation, the Juvenile Diabetes Research Foundation, the
United Mitochondrial Disease Foundation, NIH and NIAID grants, an NSERC
fellowship (B. P. H.), the Portuguese Science and Technology Foundation
(A. P. G.), the Intramural Research Program, and NIH/NHLBI (L. A. S. and
J.M.). D. A. S. is a consultant and inventor on patents licensed to
Sirtris, a GSK company. H. D., A. W. C., T. C., T. V. R., E. R. S.,
H.Z., Y.J., S. M. S., C. A. B., J.S.D., P.Y.N., R. B. P., J.L.E., and G.
P. V. are employees of Sirtris, a GSK company. Dedicated to the memories
of Jana Perni and Harmon Rasnow. A patent application on the PNC1-OPT
sirtuin assay has been filed by Harvard Medical School with D. A. S. and
B. P. H. as inventors. Patent applications related to sirtuin activators
have been filed by Sirtris and Biomol. Natural Sirt1 activators will be
provided upon request. Synthetic STACs are provided under a material
transfer agreement from Sirtris.
NR 29
TC 249
Z9 256
U1 9
U2 127
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 MAR 8
PY 2013
VL 339
IS 6124
BP 1216
EP 1219
DI 10.1126/science.1231097
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 100OG
UT WOS:000315709900051
PM 23471411
ER
PT J
AU Cibelli, J
Emborg, ME
Prockop, DJ
Roberts, M
Schatten, G
Rao, M
Harding, J
Mirochnitchenko, O
AF Cibelli, Jose
Emborg, Marina E.
Prockop, Darwin J.
Roberts, Michael
Schatten, Gerald
Rao, Mahendra
Harding, John
Mirochnitchenko, Oleg
TI Strategies for Improving Animal Models for Regenerative Medicine
SO CELL STEM CELL
LA English
DT Editorial Material
ID MYOCARDIAL-INFARCTION; CELLS
AB The field of regenerative medicine is moving toward translation to clinical practice. However, there are still knowledge gaps and safety concerns regarding stem cell-based therapies. Improving large animal models and methods for transplantation, engraftment, and imaging should help address these issues, facilitating eventual use of stem cells in the clinic.
C1 [Cibelli, Jose] Michigan State Univ, Cellular Reprogramming Lab, Dept Anim Sci, E Lansing, MI 48824 USA.
[Emborg, Marina E.] Univ Wisconsin, Dept Med Phys, Madison, WI 53715 USA.
[Emborg, Marina E.] Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA.
[Prockop, Darwin J.] Texas A&M Hlth Sci Ctr, Coll Med, Temple, TX 76502 USA.
[Prockop, Darwin J.] Inst Regenerat Med Scott & White, Dept Med, Temple, TX 76502 USA.
[Roberts, Michael] Univ Missouri, CS Bond Life Sci Ctr 240B, Columbia, MO 65211 USA.
[Schatten, Gerald] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA.
[Rao, Mahendra] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA.
[Harding, John; Mirochnitchenko, Oleg] NIH, Div Comparat Med ORIP DPCPSI OD, Bethesda, MD 20892 USA.
RP Mirochnitchenko, O (reprint author), NIH, Div Comparat Med ORIP DPCPSI OD, 6701 Democracy Blvd,Suite 943-950, Bethesda, MD 20892 USA.
EM oleg.mirochnitchenko@nih.gov
OI Schatten, Gerald/0000-0001-5206-7782
FU NICHD NIH HHS [P01 HD047675, R01 HD069979]; NIH HHS [P40 OD011050, P51
OD011106]
NR 10
TC 12
Z9 13
U1 2
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
EI 1875-9777
J9 CELL STEM CELL
JI Cell Stem Cell
PD MAR 7
PY 2013
VL 12
IS 3
BP 271
EP 274
DI 10.1016/j.stem.2013.01.004
PG 4
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 287VC
UT WOS:000329569400004
PM 23472868
ER
PT J
AU Venkataraman, G
Song, JY
Tzankov, A
Dirnhofer, S
Heinze, G
Kohl, M
Traverse-Glehen, A
Eberle, FC
Hanson, JC
Raffeld, MA
Pittaluga, S
Jaffe, ES
AF Venkataraman, Girish
Song, Joo Y.
Tzankov, Alexandar
Dirnhofer, Stephan
Heinze, Georg
Kohl, Maria
Traverse-Glehen, Alexandra
Eberle, Franziska C.
Hanson, Jeffrey C.
Raffeld, Mark A.
Pittaluga, Stefania
Jaffe, Elaine S.
TI Aberrant T-cell antigen expression in classical Hodgkin lymphoma is
associated with decreased event-free survival and overall survival
SO BLOOD
LA English
DT Article
ID REED-STERNBERG CELLS; CENTER B-CELL; IMMUNOGLOBULIN GENE REARRANGEMENTS;
PROGNOSTIC-SIGNIFICANCE; CLONAL IMMUNOGLOBULIN; RARE EXPRESSION;
DISEASE; RECEPTOR; PHENOTYPE; TRANSCRIPTION
AB Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) rarely express T-cell-associated antigens (TCA), but the clinical significance of this finding is uncertain. Fifty cHLs expressing any TCA on the HRS cells (TCA-cHL) were identified in two cohorts (National Cancer Institute, n = 38; Basel, n = 12). Diagnostic pathology data were examined in all cases with additional T-cell receptor gamma rearrangements (TRG@) polymerase chain reaction (PCR) in a subset of cases. The outcome data were compared with a cohort of cHLs negative for TCA (n = 272). Primary end points examined were event-free survival (EFS) and overall survival (OS). The median age in the TCA-cHL group was 40 years (range, 10-85 years). Seventy percent presented in low stage (stage I/II) at presentation with nodular sclerosis (NS) histology predominating in 80% of cases. Among the TCA, CD4 and CD2 were most commonly expressed, seen in 80.4% and 77.4% of cases, respectively. TRG@ PCR was negative for clonal rearrangements in 29 of 31 cases. During a median follow up of 113 months, TCA expression predicted shorter OS (adjusted hazard ratio [HRadj] = 3.32 [95% confidence interval (CI): 1.61, 6.84]; P = .001) and EFS (HRadj = 2.55 [95% CI: 1.45, 4.49]; P = .001). TCA-cHL often display NS histology, lack T-cell genotype, and are independently associated with significantly shorter OS and EFS compared with TCA-negative cHLs.
C1 [Venkataraman, Girish; Song, Joo Y.; Eberle, Franziska C.; Hanson, Jeffrey C.; Raffeld, Mark A.; Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Tzankov, Alexandar; Dirnhofer, Stephan] Univ Basel Hosp, Inst Pathol, CH-4031 Basel, Switzerland.
[Heinze, Georg; Kohl, Maria] Med Univ Vienna, Ctr Med Stat Informat & Intelligent Syst, Sect Clin Biometr, Vienna, Austria.
[Traverse-Glehen, Alexandra] Ctr Hosp Lyon Sud, Hosp Civils Lyon, Hematopathol Dept, F-69310 Pierre Benite, France.
RP Venkataraman, G (reprint author), Loyola Univ, Med Ctr, Dept Pathol, Bldg 110,Room 2222,2160 S 1st Ave, Maywood, IL 60153 USA.
EM elainejaffe@nih.gov; elainejaffe@nih.gov
RI Song, Joo/E-5356-2016;
OI Song, Joo/0000-0003-3497-2513; Venkataraman, Girish/0000-0002-8674-2608;
Jaffe, Elaine/0000-0003-4632-0301; Tzankov,
Alexandar/0000-0002-1100-3819
FU Center for Cancer Research, NCI
FX This study was supported by the intramural budget of the Center for
Cancer Research, NCI.
NR 51
TC 15
Z9 15
U1 0
U2 7
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 MAR 7
PY 2013
VL 121
IS 10
BP 1795
EP 1804
DI 10.1182/blood-2012-06-439455
PG 10
WC Hematology
SC Hematology
GA 182NZ
UT WOS:000321751800016
PM 23305738
ER
PT J
AU Kurotaki, D
Osato, N
Nishiyama, A
Yamamoto, M
Ban, T
Sato, H
Nakabayashi, J
Umehara, M
Miyake, N
Matsumoto, N
Nakazawa, M
Ozato, K
Tamura, T
AF Kurotaki, Daisuke
Osato, Naoki
Nishiyama, Akira
Yamamoto, Michio
Ban, Tatsuma
Sato, Hideaki
Nakabayashi, Jun
Umehara, Marina
Miyake, Noriko
Matsumoto, Naomichi
Nakazawa, Masatoshi
Ozato, Keiko
Tamura, Tomohiko
TI Essential role of the IRF8-KLF4 transcription factor cascade in murine
monocyte differentiation
SO BLOOD
LA English
DT Article
ID DENDRITIC CELLS; MYELOID PROGENITORS; GENE-EXPRESSION; TARGET GENES;
MACROPHAGES; IDENTIFICATION; LINEAGE; ICSBP; MICE; IMMUNODEFICIENCY
AB Monocytes regulate host defenses, inflammation, and tissue homeostasis. The transcription factor interferon regulatory factor-8 (IRF8) stimulates monocyte/macrophage differentiation, yet genome-wide understanding of the differentiation program initiated by IRF8 is lacking. By combining chromatin immunoprecipitation sequencing with gene expression profiling, we show that during IRF8-dependent monocyte differentiation, IRF8 binding occurs at both promoter-proximal and promotor-distal regions together with the transcription factor PU.1 and is associated with gene induction. Many of the promoter-distal IRF8 binding sites show an increase in histone H3 lysine 4 monomethylation, a signature for enhancers. However, about half the IRF8-induced genes were not bound by IRF8, suggesting the involvement of downstream transcription factors. Analysis of DNA motifs in cis-regulatory elements of these indirect IRF8 target genes predicted that Kruppel-like factor-4 (KLF4)-essential for Ly6C(+) monocyte development-is one such factor. Indeed, monocyte development in Irf8(-/-) mice is as defective as that in Klf4(-/-) chimeric mice. Moreover, Irf8(-/-) monocyte-dendritic cell progenitors do not express Klf4 messenger RNA. Introduction of KLF4 into an Irf8(-/-) myeloid progenitor cell line induced a subset of IRF8 target genes and caused partial monocyte differentiation. Taken together, our present results uncover genome-wide behavior of IRF8 and identify an IRF8-KLF4 axis that operates during monocyte differentiation.
C1 [Kurotaki, Daisuke; Osato, Naoki; Nishiyama, Akira; Yamamoto, Michio; Ban, Tatsuma; Sato, Hideaki; Nakabayashi, Jun; Umehara, Marina; Tamura, Tomohiko] Yokohama City Univ, Grad Sch Med, Dept Immunol, Yokohama, Kanagawa 2360004, Japan.
[Miyake, Noriko; Matsumoto, Naomichi] Yokohama City Univ, Grad Sch Med, Dept Human Genet, Yokohama, Kanagawa 2360004, Japan.
[Nakazawa, Masatoshi] Yokohama City Univ, Grad Sch Med, Dept Expt Anim Sci, Yokohama, Kanagawa 2360004, Japan.
[Ozato, Keiko] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD USA.
RP Tamura, T (reprint author), Yokohama City Univ, Grad Sch Med, Dept Immunol, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan.
EM tamurat@yokohama-cu.ac.jp
FU Japan Society for the Promotion of Science [24390246, 23659492,
24118002, 24790322, 23590343]; MEXT; Yokohama City University; Yokohama
Foundation for Advancement of Medical Science
FX This work was supported by KAKENHI grants-in-aid 24390246, 23659492, and
24118002 (T. T.), 24790322 (D. K.), and 23590343 (A.N.) from the Japan
Society for the Promotion of Science, a Special Coordination Fund for
Promoting Science and Technology "Creation of Innovation Centers for
Advanced Interdisciplinary Research Areas" from MEXT (T. T.), a grant
for Strategic Research Promotion from Yokohama City University (T. T.),
and a grant from the Yokohama Foundation for Advancement of Medical
Science (T. T.). The supercomputing resource was provided by Human
Genome Center of the Institute of Medical Science at the University of
Tokyo.
NR 45
TC 60
Z9 60
U1 0
U2 4
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 MAR 7
PY 2013
VL 121
IS 10
BP 1839
EP 1849
DI 10.1182/blood-2012-06-437863
PG 11
WC Hematology
SC Hematology
GA 182NZ
UT WOS:000321751800021
PM 23319570
ER
PT J
AU Kang, HS
Liao, G
DeGraff, LM
Gerrish, K
Bortner, CD
Garantziotis, S
Jetten, AM
AF Kang, Hong Soon
Liao, Grace
DeGraff, Laura M.
Gerrish, Kevin
Bortner, Carl D.
Garantziotis, Stavros
Jetten, Anton M.
TI CD44 Plays a Critical Role in Regulating Diet-Induced Adipose
Inflammation, Hepatic Steatosis, and Insulin Resistance
SO PLOS ONE
LA English
DT Article
ID GENE-EXPRESSION; MACROPHAGE ACCUMULATION; METABOLIC-DISORDERS; PROFILING
REVEALS; LIVER STEATOSIS; ROR-ALPHA; OBESITY; OSTEOPONTIN; DISEASE;
TISSUE
AB CD44 is a multifunctional membrane receptor implicated in the regulation of several biological processes, including inflammation. CD44 expression is elevated in liver and white adipose tissue (WAT) during obesity suggesting a possible regulatory role for CD44 in metabolic syndrome. To study this hypothesis, we examined the effect of the loss of CD44 expression on the development of various features of metabolic syndrome using CD44 null mice. Our study demonstrates that CD44-deficient mice (CD44KO) exhibit a significantly reduced susceptibility to the development of high fat-diet (HFD)-induced hepatic steatosis, WAT-associated inflammation, and insulin resistance. The decreased expression of genes involved in fatty acid synthesis and transport (Fasn and Cd36), de novo triglyceride synthesis (Mogat1), and triglyceride accumulation (Cidea, Cidec) appears in part responsible for the reduced hepatic lipid accumulation in CD44KO(HFD) mice. In addition, the expression of various inflammatory and cell matrix genes, including several chemokines and its receptors, osteopontin, and several matrix metalloproteinases and collagen genes was greatly diminished in CD44KO(HFD) liver consistent with reduced inflammation and fibrogenesis. In contrast, lipid accumulation was significantly increased in CD44KO(HFD) WAT, whereas inflammation as indicated by the reduced infiltration of macrophages and expression of macrophage marker genes, was significantly diminished in WAT of CD44KO(HFD) mice compared to WT(HFD) mice. CD44KO(HFD) mice remained considerably more insulin sensitive and glucose tolerant than WT(HFD) mice and exhibited lower blood insulin levels. Our study indicates that CD44 plays a critical role in regulating several aspects of metabolic syndrome and may provide a new therapeutic target in the management of insulin resistance.
C1 [Kang, Hong Soon; Liao, Grace; DeGraff, Laura M.; Jetten, Anton M.] NIH, Cell Biol Sect, Res Triangle Pk, NC USA.
[Gerrish, Kevin] NIH, Microarray Grp, Res Triangle Pk, NC USA.
[Bortner, Carl D.] NIEHS, Lab Signal Transduct, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Garantziotis, Stavros] NIH, Matrix Biol Sect, LRB, Res Triangle Pk, NC USA.
RP Jetten, AM (reprint author), NIH, Cell Biol Sect, Res Triangle Pk, NC USA.
EM jetten@niehs.nih.gov
RI Garantziotis, Stavros/A-6903-2009;
OI Garantziotis, Stavros/0000-0003-4007-375X; Jetten,
Anton/0000-0003-0954-4445
FU Intramural Research Program of the NIEHS, NIH [Z01-ES-101586]
FX This research was supported by the Intramural Research Program of the
NIEHS, NIH (Z01-ES-101586). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 61
TC 17
Z9 17
U1 4
U2 17
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 MAR 7
PY 2013
VL 8
IS 3
AR e58417
DI 10.1371/journal.pone.0058417
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 136BN
UT WOS:000318334500081
PM 23505504
ER
PT J
AU Dranchak, P
MacArthur, R
Guha, R
Zuercher, WJ
Drewry, DH
Auld, DS
Inglese, J
AF Dranchak, Patricia
MacArthur, Ryan
Guha, Rajarshi
Zuercher, William J.
Drewry, David H.
Auld, Douglas S.
Inglese, James
TI Profile of the GSK Published Protein Kinase Inhibitor Set Across
ATP-Dependent and-Independent Luciferases: Implications for
Reporter-Gene Assays
SO PLOS ONE
LA English
DT Article
ID FIREFLY LUCIFERASE; CHEMICAL LIBRARIES; RENILLA LUCIFERASE; POTENT
INHIBITORS; TYROSINE KINASE; ENERGY-TRANSFER; IN-VITRO; DISCOVERY;
IDENTIFICATION; BIOLUMINESCENCE
AB A library of 367 protein kinase inhibitors, the GSK Published Kinase Inhibitor Set (PKIS), which has been annotated for protein kinase family activity and is available for public screening efforts, was assayed against the commonly used luciferase reporter enzymes from the firefly, Photinus pyralis (FLuc) and marine sea pansy, Renilla reniformis (RLuc). A total of 22 compounds (similar to 6% of the library) were found to inhibit FLuc with 10 compounds showing potencies <= 1 mu M. Only two compounds were found to inhibit RLuc, and these showed relatively weak potency values (similar to 10 mu M). An inhibitor series of the VEGFR2/TIE2 protein kinase family containing either an aryl oxazole or benzimidazole-urea core illustrate the different structure activity relationship profiles FLuc inhibitors can display for kinase inhibitor chemotypes. Several FLuc inhibitors were broadly active toward the tyrosine kinase and CDK families. These data should aid in interpreting the results derived from screens employing the GSK PKIS in cell-based assays using the FLuc reporter. The study also underscores the general need for strategies such as the use of orthogonal reporters to identify kinase or non-kinase mediated cellular responses.
C1 [Dranchak, Patricia; MacArthur, Ryan; Guha, Rajarshi; Auld, Douglas S.; Inglese, James] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA.
[Inglese, James] NHGRI, NIH, Bethesda, MD 20892 USA.
[Zuercher, William J.; Drewry, David H.] GlaxoSmithKline, Dept Biol Chem, Res Triangle Pk, NC USA.
RP Inglese, J (reprint author), NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA.
EM jinglese@mail.nih.gov
FU NIH Roadmap for Medical Research
FX This work was supported by the NIH Roadmap for Medical Research (J.I.
and D.S.A.). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 44
TC 20
Z9 20
U1 0
U2 16
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 7
PY 2013
VL 8
IS 3
AR e57888
DI 10.1371/journal.pone.0057888
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 136BN
UT WOS:000318334500037
PM 23505445
ER
PT J
AU Hagglund, MGA
Roshanbin, S
Lofqvist, E
Hellsten, SV
Nilsson, VCO
Todkar, A
Zhu, YN
Stephansson, O
Drgonova, J
Uhl, GR
Schioth, HB
Fredriksson, R
AF Hagglund, Maria G. A.
Roshanbin, Sahar
Lofqvist, Erik
Hellsten, Sofie V.
Nilsson, Victor C. O.
Todkar, Aniruddha
Zhu, Yinan
Stephansson, Olga
Drgonova, Jana
Uhl, George R.
Schioth, Helgi B.
Fredriksson, Robert
TI B(0)AT2 (SLC6A15) Is Localized to Neurons and Astrocytes, and Is
Involved in Mediating the Effect of Leucine in the Brain
SO PLOS ONE
LA English
DT Article
ID AMINO-ACID TRANSPORTER; CENTRAL-NERVOUS-SYSTEM; BINDING INHIBITOR DBI;
REGULATES FOOD-INTAKE; ORPHAN TRANSPORTER; EXPRESSION PATTERN; V7-3
SLC6A15; PROTEIN; RAT; CHAIN
AB The B(0)AT2 protein is a product of the SLC6A15 gene belonging to the SLC6 subfamily and has been shown to be a transporter of essential branched-chain amino acids. We aimed to further characterize the B(0)AT2 transporter in CNS, and to use Slc6a15 knock out (KO) mice to investigate whether B(0)AT2 is important for mediating the anorexigenic effect of leucine. We used the Slc6a15 KO mice to investigate the role of B(0)AT2 in brain in response to leucine and in particular the effect on food intake. Slc6a15 KO mice show lower reduction of food intake as well as lower neuronal activation in the ventromedial hypothalamic nucleus (VMH) in response to leucine injections compared to wild type mice. We also used RT-PCR on rat tissues, in situ hybridization and immunohistochemistry on mouse CNS tissues to document in detail the distribution of SLC6A15 on gene and protein levels. We showed that B(0)AT2 immunoreactivity is mainly neuronal, including localization in many GABAergic neurons and spinal cord motor neurons. B(0)AT2 immunoreactivity was also found in astrocytes close to ventricles, and co-localized with cytokeratin and diazepam binding inhibitor (DBI) in epithelial cells of the choroid plexus. The data suggest that B(0)AT2 play a role in leucine homeostasis in the brain.
C1 [Hagglund, Maria G. A.; Roshanbin, Sahar; Lofqvist, Erik; Hellsten, Sofie V.; Nilsson, Victor C. O.; Todkar, Aniruddha; Zhu, Yinan; Stephansson, Olga; Schioth, Helgi B.; Fredriksson, Robert] Uppsala Univ, Dept Neurosci, Uppsala, Sweden.
[Drgonova, Jana; Uhl, George R.] NIDA, Mol Neurobiol Branch, NIH, Baltimore, MD USA.
RP Fredriksson, R (reprint author), Uppsala Univ, Dept Neurosci, Uppsala, Sweden.
EM Robert.Fredriksson@neuro.uu.se
OI Drgonova, Jana/0000-0002-4623-8466
FU Swedish Research Council; Ahlens Foundation; Novo Nordisk Foundation;
Goran Gustafsson Foundation; Engkvist Foundation; Magnus Bergvall
Foundation; National Institutes of Health Intramural Research Program
(NIDA)
FX This study was supported by the Swedish Research Council as well as the
Ahlens Foundation, the Novo Nordisk Foundation, the Goran Gustafsson
Foundation, Engkvist Foundation and Magnus Bergvall Foundation, and the
National Institutes of Health Intramural Research Program (NIDA). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 64
TC 6
Z9 6
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 MAR 7
PY 2013
VL 8
IS 3
AR e58651
DI 10.1371/journal.pone.0058651
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 136BN
UT WOS:000318334500110
PM 23505546
ER
PT J
AU Rajadas, J
Sun, WC
Li, H
Inayathullah, M
Cereghetti, D
Tan, A
Coelho, VD
Chrest, FJ
Kusiak, JW
Smith, WW
Taub, D
Wu, JC
Rifkind, JM
AF Rajadas, Jayakumar
Sun, Wenchao
Li, Hai
Inayathullah, Mohammed
Cereghetti, Damiano
Tan, Aaron
Coelho, Valeria de Mello
Chrest, Francis J.
Kusiak, John W.
Smith, Wanli Wei
Taub, Dennis
Wu, Joseph C.
Rifkind, Joseph M.
TI Enhanced A beta(1-40) Production in Endothelial Cells Stimulated with
Fibrillar A beta(1-42)
SO PLOS ONE
LA English
DT Article
ID AMYLOID-BETA PEPTIDE; BLOOD-BRAIN-BARRIER; NITRIC-OXIDE SYNTHASE;
SMOOTH-MUSCLE-CELLS; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; POSSIBLE
INVOLVEMENT; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; IN-VITRO
AB Amyloid accumulation in the brain of Alzheimer's patients results from altered processing of the 39- to 43-amino acid amyloid beta protein (A beta). The mechanisms for the elevated amyloid (A beta(1-42)) are considered to be over-expression of the amyloid precursor protein (APP), enhanced cleavage of APP to A beta, and decreased clearance of A beta from the central nervous system (CNS). We report herein studies of A beta stimulated effects on endothelial cells. We observe an interesting and as yet unprecedented feedback effect involving A beta(1-42) fibril-induced synthesis of APP by Western blot analysis in the endothelial cell line Hep-1. We further observe an increase in the expression of A beta(1-40) by flow cytometry and fluorescence microscopy. This phenomenon is reproducible for cultures grown both in the presence and absence of serum. In the former case, flow cytometry reveals that A beta(1-40) accumulation is less pronounced than under serum-free conditions. Immunofluorescence staining further corroborates these observations. Cellular responses to fibrillar A beta(1-42) treatment involving eNOS upregulation and increased autophagy are also reported.
C1 [Rifkind, Joseph M.] NIA, Mol Dynam Sect, Baltimore, MD 21224 USA.
[Coelho, Valeria de Mello; Taub, Dennis] NIA, Immunol Lab, Baltimore, MD 21224 USA.
[Chrest, Francis J.; Kusiak, John W.; Smith, Wanli Wei] NIA, Res Resources Branch, Baltimore, MD 21224 USA.
[Rajadas, Jayakumar; Sun, Wenchao; Li, Hai; Inayathullah, Mohammed; Cereghetti, Damiano] Stanford Univ, Sch Med, Biomat & Adv Drug Delivery Lab, Stanford, CA 94305 USA.
[Tan, Aaron] UCL, UCL Med Sch, UCL Div Surg & Intervent Sci, Ctr Nanotechnol & Regenerat Med, London WC1E 6BT, England.
[Wu, Joseph C.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Wu, Joseph C.] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
RP Rajadas, J (reprint author), Stanford Univ, Sch Med, Biomat & Adv Drug Delivery Lab, Stanford, CA 94305 USA.
EM jayraja@stanford.edu; rifkindj@mail.nih.gov
RI Inayathullah, Mohammed/C-6953-2015
OI Inayathullah, Mohammed/0000-0001-7646-1709
FU Intramural Research Program the National Institute of Health; National
Institute on Aging; National Institute of Health [HL095571]
FX This research was in part supported by the Intramural Research Program
the National Institute of Health, National Institute on Aging and
National Institute of Health HL095571. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 56
TC 8
Z9 8
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 MAR 7
PY 2013
VL 8
IS 3
AR e58194
DI 10.1371/journal.pone.0058194
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 136BN
UT WOS:000318334500058
PM 23505467
ER
PT J
AU Sproull, M
Avondoglio, D
Kramp, T
Shankavaram, U
Camphausen, K
AF Sproull, Mary
Avondoglio, Dane
Kramp, Tamalee
Shankavaram, Uma
Camphausen, Kevin
TI Correlation of Plasma FL Expression with Bone Marrow Irradiation Dose
SO PLOS ONE
LA English
DT Article
ID TOTAL-BODY IRRADIATION; ACUTE LYMPHOBLASTIC-LEUKEMIA;
ACUTE-RADIATION-SYNDROME; LIGAND CONCENTRATION; URINE BIOSPECIMENS;
HEMATOPOIESIS; MICE; TRANSPLANTATION; CHEMOTHERAPY; BIODOSIMETRY
AB Purpose: Ablative bone marrow irradiation is an integral part of hematopoietic stem cell transplantation. These treatment regimens are based on classically held models of radiation dose and the bone marrow response. Flt-3 ligand (FL) has been suggested as a marker of hematopoiesis and bone marrow status but the kinetics of its response to bone marrow irradiation has yet to be fully characterized. In the current study, we examine plasma FL response to total body and partial body irradiation in mice and its relationship with irradiation dose, time of collection and pattern of bone marrow exposure.
Materials/Methods: C57BL6 mice received a single whole body or partial body irradiation dose of 1-8 Gy. Plasma was collected by mandibular or cardiac puncture at 24, 48 and 72 hr post-irradiation as well as 1-3 weeks post-irradiation. FL levels were determined via ELISA assay and used to generate two models: a linear regression model and a gated values model correlating plasma FL levels with radiation dose.
Results: At all doses between 1-8 Gy, plasma FL levels were greater than control and the level of FL increased proportionally to the total body irradiation dose. Differences in FL levels were statistically significant at each dose and at all time points. Partial body irradiation of the trunk areas, encompassing the bulk of the hematopoietically active bone marrow, resulted in significantly increased FL levels over control but irradiation of only the head or extremities did not. FL levels were used to generate a dose prediction model for total body irradiation. In a blinded study, the model differentiated mice into dose received cohorts of 1, 4 or 8 Gy based on plasma FL levels at 24 or 72 hrs post-irradiation.
Conclusion: Our findings indicate that plasma FL levels might be used as a marker of hematopoietically active bone marrow and radiation exposure in mice.
C1 [Sproull, Mary; Avondoglio, Dane; Kramp, Tamalee; Shankavaram, Uma; Camphausen, Kevin] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, Bldg 10, Bethesda, MD 20892 USA.
EM camphauk@mail.nih.gov
NR 50
TC 5
Z9 5
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 7
PY 2013
VL 8
IS 3
AR e58558
DI 10.1371/journal.pone.0058558
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 136BN
UT WOS:000318334500101
PM 23505536
ER
PT J
AU Yuan, JM
Jin, CH
Qin, HD
Wang, JD
Sha, WW
Wang, MZ
Zhang, YB
Zhang, FQ
Li, JJ
Li, JF
Yu, S
Qi, SG
Shugart, YY
AF Yuan, Jianmin
Jin, Chunhui
Qin, Hai-De
Wang, Jidong
Sha, Weiwei
Wang, Mingzhong
Zhang, Yunbiao
Zhang, Fuquan
Li, Jijiang
Li, Jianfeng
Yu, Shui
Qi, Shuguang
Shugart, Yin Yao
TI Replication Study Confirms Link between TSPAN18 Mutation and
Schizophrenia in Han Chinese
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; COMMON VARIANTS; MENTAL-RETARDATION; BIPOLAR
DISORDER; RISK
AB Schizophrenia (SCZ) is a severe psychiatric disorder associated with many different risk factors, both genetic and environmental. A recent genome-wide association study (GWAS) of Han Chinese identified three single-nucleotide polymorphisms (SNPs rs11038167, rs11038172, and rs835784) in the tetraspanins gene TSPAN18 as possible susceptibility loci for schizophrenia. Hoping to validate these findings, we conducted a case-control study of Han Chinese with 1093 schizophrenia cases and 1022 healthy controls. Using the LDR-PCR method to genotype polymorphisms in TSPAN18, we found no significant differences (P>0.05) between patients and controls in either the allele or genotype frequency of the SNPs rs11038167 and rs11038172. We did find, however, that the frequency of the 'A' allele of SNP rs835784 is significantly higher in patients than in controls. We further observed a significant association (OR = 1.197, 95% CI = 1.047-1.369) between risk for SCZ and this 'A' allele. These results confirm the significant association, in Han Chinese populations, of increased SCZ risk and the variant of the TSPAN18 gene containing the 'A' allele of SNP rs835784.
C1 [Yuan, Jianmin; Jin, Chunhui; Wang, Jidong; Zhang, Yunbiao; Zhang, Fuquan; Yu, Shui; Qi, Shuguang] Wuxi Mental Hlth Ctr, Wuxi, Jiangsu, Peoples R China.
[Jin, Chunhui] Jiangsu Inst Psychol, Wuxi, Jiangsu, Peoples R China.
[Qin, Hai-De; Shugart, Yin Yao] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Sha, Weiwei; Li, Jijiang] Yangzhou Wutaishan Hosp, Yangzhou, Jiangsu, Peoples R China.
[Wang, Mingzhong; Li, Jianfeng] Nanjing Qinglongshan Mental Hosp, Nanjing, Jiangsu, Peoples R China.
RP Qi, SG (reprint author), Wuxi Mental Hlth Ctr, Wuxi, Jiangsu, Peoples R China.
EM shuguangqi0208@126.com; kay1yao@mail.nih.gov
FU Key Characteristic Specialty/Discipline of Wuxi Hospital Management
Center; Wuxi Municipal Health Bureau [Q201208]; Intramural Research
Program at the National Institute of Mental Health (NIMH)
FX This work was supported by a grant from the Key Characteristic
Specialty/Discipline of Wuxi Hospital Management Center, from the
Research Project of the Wuxi Municipal Health Bureau (Q201208). HDQ and
YYS are supported by supported by the Intramural Research Program at the
National Institute of Mental Health (NIMH). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript. The views expressed in this presentation
do not necessarily represent the views of the NIMH, National Institutes
of Health, Health and Human Services, or the United States Government.
NR 19
TC 13
Z9 14
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 MAR 7
PY 2013
VL 8
IS 3
AR e58785
DI 10.1371/journal.pone.0058785
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 136BN
UT WOS:000318334500127
PM 23505562
ER
PT J
AU Gonzalez-Caballero, N
Valenzuela, JG
Mc Ribeiro, J
Cuervo, P
Brazil, RP
AF Gonzalez-Caballero, Natalia
Valenzuela, Jesus G.
Mc Ribeiro, Jose
Cuervo, Patricia
Brazil, Reginaldo P.
TI Transcriptome exploration of the sex pheromone gland of Lutzomyia
longipalpis (Diptera: Psychodidae: Phlebotominae)
SO PARASITES & VECTORS
LA English
DT Article
DE Lutzomyia longipalpis; Male pheromone gland; Transcriptome; Mevalonate
pathway
ID FARNESYL-DIPHOSPHATE-SYNTHASE; COTTON BOLL-WEEVIL; HMG-COA REDUCTASE;
GREEN PEACH APHID; MEVALONATE PATHWAY; JUVENILE-HORMONE; IPS-PINI;
VISCERAL LEISHMANIASIS; BINDING-PROTEINS; SPECIES COMPLEX
AB Background: Molecules involved in pheromone biosynthesis may represent alternative targets for insect population control. This may be particularly useful in managing the reproduction of Lutzomyia longipalpis, the main vector of the protozoan parasite Leishmania infantum in Latin America. Besides the chemical identity of the major components of the L. longipalpis sex pheromone, there is no information regarding the molecular biology behind its production. To understand this process, obtaining information on which genes are expressed in the pheromone gland is essential.
Methods: In this study we used a transcriptomic approach to explore the pheromone gland and adjacent abdominal tergites in order to obtain substantial general sequence information. We used a laboratory-reared L. longipalpis (one spot, 9-Methyl GermacreneB) population, captured in Lapinha Cave, state of Minas Gerais, Brazil for this analysis.
Results: From a total of 3,547 cDNA clones, 2,502 high quality sequences from the pheromone gland and adjacent tissues were obtained and assembled into 1,387 contigs. Through blast searches of public databases, a group of transcripts encoding proteins potentially involved in the production of terpenoid precursors were identified in the 4th abdominal tergite, the segment containing the pheromone gland. Among them, protein-coding transcripts for four enzymes of the mevalonate pathway such as 3-hydroxyl-3-methyl glutaryl CoA reductase, phosphomevalonate kinase, diphosphomevalonate descarboxylase, and isopentenyl pyrophosphate isomerase were identified. Moreover, transcripts coding for farnesyl diphosphate synthase and NADP+ dependent farnesol dehydrogenase were also found in the same tergite. Additionally, genes potentially involved in pheromone transportation were identified from the three abdominal tergites analyzed.
Conclusion: This study constitutes the first transcriptomic analysis exploring the repertoire of genes expressed in the tissue containing the L. longipalpis pheromone gland as well as the flanking tissues. Using a comparative approach, a set of molecules potentially present in the mevalonate pathway emerge as interesting subjects for further study regarding their association to pheromone biosynthesis. The sequences presented here may be used as a reference set for future research on pheromone production or other characteristics of pheromone communication in this insect. Moreover, some matches for transcripts of unknown function may provide fertile ground of an in-depth study of pheromone-gland specific molecules.
C1 [Gonzalez-Caballero, Natalia; Brazil, Reginaldo P.] Fiocruz MS, IOC, Lab Bioquim & Fisiol Insetos, BR-21040360 Rio De Janeiro, RJ, Brazil.
[Valenzuela, Jesus G.; Mc Ribeiro, Jose] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Cuervo, Patricia] Fiocruz MS, IOC, Lab Pesquisa Leishmaniose, BR-21040360 Rio De Janeiro, RJ, Brazil.
RP Brazil, RP (reprint author), Fiocruz MS, IOC, Lab Bioquim & Fisiol Insetos, Av Brasil 4365,Sala 213, BR-21040360 Rio De Janeiro, RJ, Brazil.
EM rpbrazil@ioc.fiocruz.br
RI Cuervo, Patricia/F-9896-2012;
OI Ribeiro, Jose/0000-0002-9107-0818
FU Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES);
Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ);
Division of Intramural Research, the National Institute of Allergy and
Infectious Disease
FX This work was supported by the Coordenacao de Aperfeicoamento de Pessoal
de Nivel Superior (CAPES), Fundacao de Amparo a Pesquisa do Estado do
Rio de Janeiro (FAPERJ) and the Division of Intramural Research, the
National Institute of Allergy and Infectious Disease. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 108
TC 5
Z9 5
U1 4
U2 33
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-3305
J9 PARASITE VECTOR
JI Parasites Vectors
PD MAR 7
PY 2013
VL 6
AR 56
DI 10.1186/1756-3305-6-56
PG 16
WC Parasitology
SC Parasitology
GA 129GC
UT WOS:000317826000001
PM 23497448
ER
PT J
AU Robinson, OJ
Krimsky, M
Grillon, C
AF Robinson, Oliver J.
Krimsky, Marissa
Grillon, Christian
TI The impact of induced anxiety on response inhibition
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE anxiety; threat; threat of shock; response inhibition; mind-wandering
ID SUSTAINED ATTENTION; PREPULSE INHIBITION; SHOCK; COGNITION; THREAT;
MIND; STARTLE; VIGILANCE; EMOTION; TASK
AB Anxiety has wide reaching effects on cognition; evidenced most prominently by the "difficulties concentrating" seen in anxiety disorders, and by adaptive harm-avoidant behaviors adopted under threatening circumstances. Despite having critical implications for daily-living, the precise impact of anxiety on cognition is as yet poorly quantified. Here we attempt to clarify the impact of anxiety on sustained attention and response inhibition via a translational anxiety induction in healthy individuals (N = 22). Specifically, in a within-subjects design, participants completed the Sustained Attention to Response Task (SART) in which subjects withhold responses to infrequent no-go stimuli under threat of unpredictable electrical shock (anxious) and safe (non-anxious) conditions. Different studies have argued that this task measures either (1) attention lapses due to off-task thinking or (2) response inhibition; two cognitive functions which are likely impacted by anxiety. We show that threat of shock significantly reduces errors of commission on the no-go trials relative to the safe condition whilst having no effect on go trials or overall reaction time (RT). We suggest that this is because threat of shock during SART promotes response inhibition. In particular we argue that, by virtue of frequency, subjects acquire a habitual bias toward a go response which impairs no-go performance and that threat of shock improves the ability to withhold these prepotent responses. This improved response inhibition likely falls within the range of adaptive cognitive functions which promote cautious harm avoidance under threatening conditions, although a range of alternative explanations for this effect is discussed.
C1 [Robinson, Oliver J.; Krimsky, Marissa; Grillon, Christian] NIMH, Sect Neurobiol Fear & Anxiety, Bethesda, MD 20892 USA.
RP Robinson, OJ (reprint author), NIMH, Sect Neurobiol Fear & Anxiety, 15K North Dr, Bethesda, MD 20892 USA.
EM oliver.j.robinson@gmail.com
OI Robinson, Oliver/0000-0002-3100-1132
FU National Institutes of Mental Health
FX This research was supported by the Intramural Research Program of the
National Institutes of Mental Health.
NR 39
TC 15
Z9 15
U1 6
U2 40
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD MAR 7
PY 2013
VL 7
AR 69
DI 10.3389/fnhum.2013.00069
PG 5
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA 107XC
UT WOS:000316253200001
PM 23471118
ER
PT J
AU Wang, YC
Leung, JW
Jiang, YJ
Lowery, MG
Do, H
Vasquez, KM
Chen, JJ
Wang, WD
Li, L
AF Wang, Yucai
Leung, Justin W.
Jiang, Yingjun
Lowery, Megan G.
Do, Huong
Vasquez, Karen M.
Chen, Junjie
Wang, Weidong
Li, Lei
TI FANCM and FAAP24 Maintain Genome Stability via Cooperative as Well as
Unique Functions
SO MOLECULAR CELL
LA English
DT Article
ID ANEMIA CORE COMPLEX; CROSS-LINK REPAIR; COMPLEMENTATION GROUP-M;
NUCLEOTIDE EXCISION-REPAIR; DNA-DAMAGE; MONOUBIQUITINATED FANCD2;
BINDING-PROTEIN; BLOOM-SYNDROME; REPLICATION; PATHWAY
AB The DNA remodeling enzyme FANCM and its DNA-binding partner, FAAP24, constitute a complex involved in the activation of Fanconi anemia (FA) DNA damage response mechanism, but neither gene has distinct patient mutants. In this study, we created isogenic models for both FANCM and FAAP24 and investigated their integrated functions in DNA damage response. We found that FANCM and FAAP24 coordinately facilitate FA pathway activation and suppress sister chromatid exchange. Importantly, we show that FANCM and FAAP24 possess nonoverlapping functions such that FAAP24 promotes ATR-mediated checkpoint activation particularly in response to DNA crosslinking agents, whereas FANCM participates in recombination-independent interstrand crosslink repair by facilitating recruitment of lesion incision activities, which requires its translocase activity. Our data suggest that FANCM and FAAP24 play multiple, while not fully epistatic, roles in maintaining genomic integrity.
C1 [Wang, Yucai; Leung, Justin W.; Jiang, Yingjun; Do, Huong; Chen, Junjie; Li, Lei] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA.
[Lowery, Megan G.; Vasquez, Karen M.] Univ Texas MD Anderson Canc Ctr, Dept Mol Carcinogenesis, Houston, TX 77030 USA.
[Li, Lei] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
[Wang, Yucai; Chen, Junjie; Li, Lei] Univ Texas Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA.
[Wang, Weidong] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
RP Li, L (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM leili@mdanderson.org
RI Jiang, Yingjun/I-8919-2014
FU Intramural Research Program of the National Institute on Aging
[AG000688-07]; National Institute of Health; CPRIT (Multi-Investigator
Award) [RP110465-P2]; National Cancer Institute [CA127945, CA097175];
Department of Defense [W81XWH-05-1-0470]
FX The authors wish to thank Dr. Zhenghe Wang for providing reagents and
technical advice on rAAV-based targeting and Drs. Lee Zou and Junran
Zhang for technical advices on RPA2 immunostaining. This work was
supported in part by the Intramural Research Program of the National
Institute on Aging (AG000688-07), National Institute of Health (W.W.)
and by grants from CPRIT (Multi-Investigator Award; RP110465-P2 to J.C.)
and the National Cancer Institute (CA127945 and CA097175 Project 3 to
L.L). eChIP substrates preparation and clonogenic survivals were
assisted respectively by Core C and Core B (CA097175). J.C. is a
recipient of an Era of Hope Scholar award from the Department of Defense
(W81XWH-05-1-0470).
NR 50
TC 27
Z9 28
U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD MAR 7
PY 2013
VL 49
IS 5
BP 997
EP 1009
DI 10.1016/j.molcel.2012.12.010
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 106TQ
UT WOS:000316168000020
PM 23333308
ER
PT J
AU Williams, JS
Smith, DJ
Marjavaara, L
Lujan, SA
Chabes, A
Kunkel, TA
AF Williams, Jessica S.
Smith, Dana J.
Marjavaara, Lisette
Lujan, Scott A.
Chabes, Andrei
Kunkel, Thomas A.
TI Topoisomerase 1-Mediated Removal of Ribonucleotides from Nascent
Leading-Strand DNA
SO MOLECULAR CELL
LA English
DT Article
ID BASE EXCISION-REPAIR; SACCHAROMYCES-CEREVISIAE; MISMATCH REPAIR;
SUBSTRATE-SPECIFICITY; POLYMERASE-EPSILON; DNTP POOLS; RNASE-H;
REPLICATION; YEAST; TRANSCRIPTION
AB RNase H2-dependent ribonucleotide excision repair (RER) removes ribonucleotides incorporated during DNA replication. When RER is defective, ribonucleotides in the nascent leading strand of the yeast genome are associated with replication stress and genome instability. Here, we provide evidence that topoisomerase 1 (Top1) initiates an independent form of repair to remove ribonucleotides from genomic DNA. This Top1-dependent process activates the S phase checkpoint. Deleting TOP1 reverses this checkpoint activation and also relieves replication stress and genome instability in RER-defective cells. The results reveal an additional removal pathway for a very common lesion in DNA, and they imply that the "dirty" DNA ends created when Top1 incises ribonucleotides in DNA are responsible for the adverse consequences of ribonucleotides in RNase H2-defective cells.
C1 [Williams, Jessica S.; Smith, Dana J.; Lujan, Scott A.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Williams, Jessica S.; Smith, Dana J.; Lujan, Scott A.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Marjavaara, Lisette; Chabes, Andrei] Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden.
[Chabes, Andrei] Umea Univ, Lab Mol Infect Med Sweden, S-90187 Umea, Sweden.
RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
OI Chabes, Andrei/0000-0003-1708-8259
FU Division of Intramural Research of the National Institutes of Health,
National Institute of Environmental Health Sciences [Z01 ES065070];
Swedish Foundation for Strategic Research; Swedish Research Council;
Swedish Cancer Society
FX We thank Michelle Heacock and Scott Williams for helpful comments on the
manuscript and Kunkel lab members for data previously generated in the
lab and useful discussions. We are grateful to Grace Kiss ling for
statistical advice and Carl Bortner for expert assistance with flow
cytometry analysis. We also acknowledge the National Institute of
Environmental Health Sciences Molecular Genetics Core Facility for
sequence analysis of 5-FOA-resistant mutants and the Flow Cytometry
Center for FACS analysis. This work was supported by Project Z01
ES065070 (to T.A.K.) from the Division of Intramural Research of the
National Institutes of Health, National Institute of Environmental
Health Sciences, and by the Swedish Foundation for Strategic Research,
the Swedish Research Council, and the Swedish Cancer Society (to A.G.).
NR 32
TC 51
Z9 51
U1 1
U2 18
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD MAR 7
PY 2013
VL 49
IS 5
BP 1010
EP 1015
DI 10.1016/j.molcel.2012.12.021
PG 6
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 106TQ
UT WOS:000316168000021
PM 23375499
ER
PT J
AU Sakakibara, S
Espigol-Frigole, G
Gasperini, P
Uldrick, TS
Yarchoan, R
Tosato, G
AF Sakakibara, S.
Espigol-Frigole, G.
Gasperini, P.
Uldrick, T. S.
Yarchoan, R.
Tosato, G.
TI A20/TNFAIP3 inhibits NF-kappa B activation induced by the Kaposi's
sarcoma-associated herpesvirus vFLIP oncoprotein
SO ONCOGENE
LA English
DT Article
DE KSHV; NF-kappa B; vFLIP/K13; endothelial cells; Kaposi's sarcoma; AIDS
ID ZINC-FINGER PROTEIN; DEPENDENT GENE-EXPRESSION; KINASE COMPLEX;
IKK-GAMMA; ENDOTHELIAL-CELLS; TRANSCRIPTION FACTOR; UBIQUITIN CHAINS;
A20 INTERACTS; KSHV VFLIP; ENZYME A20
AB Kaposi's sarcoma-associated herpesvirus (KSHV) K13/vFLIP (viral Flice-inhibitory protein) induces transcription of numerous genes through NF-kappa B activation, including pro-inflammatory cytokines, which contribute to the pathogenesis of Kaposi's sarcoma (KS). In this study, we report that KSHV vFLIP induces the expression of the NF-kappa B regulatory proteins A20, ABIN-1 and ABIN-3 (A20-binding NF-kappa B inhibitors) in primary human endothelial cells, and that KS spindle cells express A20 in KS tissue. In reporter assays, A20 strongly impaired vFLIP-induced NF-kappa B activation in 293T cells, but ABIN-1 and ABIN-3 did not. Mutational analysis established that the C-terminal domain (residues 427-790) is critical for A20 modulation of NF-kappa B, but the ubiquitin-editing OTU (ovarian tumor) domain is not. In functional assays, A20 inhibited vFLIP-induced expression of the chemokine IP-10, reduced vFLIP-induced cell proliferation and increased IKK1 protein levels. Thus, we demonstrate that A20 negatively regulates NF-kappa B activation directly induced by KSHV vFLIP. By attenuating excessive and prolonged vFLIP-induced NF-kappa B activation that could be harmful to KSHV-infected cells, A20 likely has an important role in the pathogenesis of KSHV-associated diseases, in which vFLIP is expressed. Oncogene (2013) 32, 1223-1232; doi:10.1038/onc.2012.145; published online 23 April 2012
C1 [Sakakibara, S.; Espigol-Frigole, G.; Gasperini, P.; Tosato, G.] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Uldrick, T. S.; Yarchoan, R.] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Espigol-Frigole, G (reprint author), NCI, Cellular Oncol Lab, CCR, NIH, Bldg 37,Room 4134, Bethesda, MD 20892 USA.
EM GESPIGOL@clinic.ub.es
FU intramural research program in Center for Cancer Research, National
Cancer Institute, National Institutes of Health, Bethesda, USA
FX We thank G Nolan (Stanford University), BK Weaver (Missouri State
University), J-M Peloponese Jr, K-T Jeang (NIAID, NIH), DB Conze, JD
Ashwell (NCI, NIH), AV Grishin (University of Southern California), A
Leonardi (University of Naples, Italy), R Lin (Jewish General Hospital,
Canada) for reagents; the patients who volunteered for this study; Dr MN
Polizzotto (NCI, NIH), K Aleman and K Wyvill for patient care; the
Confocal Microscopy Core Facility (Laboratory of Experimental
Carcinogenesis, CCR, NCI) for providing LSM510 and the DNA Minicore
Facility (Laboratory of Experimental Carcinogenesis, CCR, NCI) for DNA
sequencing, and K Sakakibara (NCI, NIH) for her help in reporter assay.
We also thank Drs D Lowy, O Salvucci, H Ohnuki and all members of
Laboratory of Cellular Oncology Branch for their advice and help on this
work. This study was supported by the intramural research program in
Center for Cancer Research, National Cancer Institute, National
Institutes of Health, Bethesda, MD20892, USA.
NR 65
TC 5
Z9 9
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAR 7
PY 2013
VL 32
IS 10
BP 1223
EP 1232
DI 10.1038/onc.2012.145
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 110OP
UT WOS:000316454500003
PM 22525270
ER
PT J
AU Wagner, KU
Booth, BW
Boulanger, CA
Smith, GH
AF Wagner, K-U
Booth, B. W.
Boulanger, C. A.
Smith, G. H.
TI Multipotent PI-MECs are the true targets of MMTV-neu tumorigenesis
SO ONCOGENE
LA English
DT Letter
ID MAMMARY EPITHELIAL-CELLS; STEM
C1 [Wagner, K-U] Univ Nebraska Med Ctr, Omaha, NE 68198 USA.
[Booth, B. W.] Clemson Univ, Clemson, NC USA.
[Boulanger, C. A.; Smith, G. H.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Wagner, KU (reprint author), Univ Nebraska Med Ctr, Omaha, NE 68198 USA.
EM gs4d@nih.gov
RI Wagner, Kay-Uwe/B-6044-2009
NR 6
TC 4
Z9 4
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAR 7
PY 2013
VL 32
IS 10
BP 1338
EP 1338
DI 10.1038/onc.2012.452
PG 1
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 110OP
UT WOS:000316454500014
PM 23045277
ER
PT J
AU Broderick, JP
Palesch, YY
Demchuk, AM
Yeatts, SD
Khatri, P
Hill, MD
Jauch, EC
Jovin, TG
Yan, B
Silver, FL
von Kummer, R
Molina, CA
Demaerschalk, BM
Budzik, R
Clark, WM
Zaidat, OO
Malisch, TW
Goyal, M
Schonewille, WJ
Mazighi, M
Engelter, ST
Anderson, C
Spilker, J
Carrozzella, J
Ryckborst, KJ
Janis, LS
Martin, RH
Foster, LD
Tomsick, TA
AF Broderick, Joseph P.
Palesch, Yuko Y.
Demchuk, Andrew M.
Yeatts, Sharon D.
Khatri, Pooja
Hill, Michael D.
Jauch, Edward C.
Jovin, Tudor G.
Yan, Bernard
Silver, Frank L.
von Kummer, Ruediger
Molina, Carlos A.
Demaerschalk, Bart M.
Budzik, Ronald
Clark, Wayne M.
Zaidat, Osama O.
Malisch, Tim W.
Goyal, Mayank
Schonewille, Wouter J.
Mazighi, Mikael
Engelter, Stefan T.
Anderson, Craig
Spilker, Judith
Carrozzella, Janice
Ryckborst, Karla J.
Janis, L. Scott
Martin, Renee H.
Foster, Lydia D.
Tomsick, Thomas A.
CA Interventional Management Stroke
TI Endovascular Therapy after Intravenous t-PA versus t-PA Alone for Stroke
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ACUTE ISCHEMIC-STROKE; PERCUTANEOUS CORONARY INTERVENTION;
TISSUE-PLASMINOGEN ACTIVATOR; MYOCARDIAL-INFARCTION; CLINICAL-TRIALS;
POOLED ANALYSIS; MERCI TRIAL; III TRIAL; MANAGEMENT; TIME
AB BACKGROUND
Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a combined approach is more effective than intravenous t-PA alone is uncertain.
METHODS
We randomly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone, in a 2: 1 ratio. The primary outcome measure was a modified Rankin scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability).
RESULTS
The study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage points; 95% confidence interval [CI], -6.1 to 9.1, with adjustment for the National Institutes of Health Stroke Scale [NIHSS] score [8-19, indicating moderately severe stroke, or >= 20, indicating severe stroke]), nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8 percentage points; 95% CI, -4.4 to 18.1) and those with a score of 19 or lower (-1.0 percentage point; 95% CI, -10.8 to 8.8). Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively; P = 0.52) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P = 0.83).
CONCLUSIONS
The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA, as compared with intravenous t-PA alone. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00359424.)
C1 [Broderick, Joseph P.; Khatri, Pooja; Spilker, Judith; Carrozzella, Janice; Tomsick, Thomas A.] Univ Cincinnati, Acad Hlth Ctr, Inst Neurosci, Dept Neurol, Cincinnati, OH 45267 USA.
[Broderick, Joseph P.; Khatri, Pooja; Spilker, Judith; Carrozzella, Janice; Tomsick, Thomas A.] Univ Cincinnati, Acad Hlth Ctr, Inst Neurosci, Dept Rehabil Med & Radiol, Cincinnati, OH 45267 USA.
[Palesch, Yuko Y.; Yeatts, Sharon D.; Foster, Lydia D.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC USA.
[Jauch, Edward C.] Med Univ S Carolina, Div Emergency Med, Charleston, SC USA.
[Demchuk, Andrew M.; Hill, Michael D.; Goyal, Mayank; Ryckborst, Karla J.] Univ Calgary, Hotchkiss Brain Inst, Seaman Family Magnet Resonance Res Ctr, Dept Clin Neurosci, Calgary, AB, Canada.
[Demchuk, Andrew M.; Hill, Michael D.; Goyal, Mayank; Ryckborst, Karla J.] Univ Calgary, Hotchkiss Brain Inst, Seaman Family Magnet Resonance Res Ctr, Dept Radiol, Calgary, AB, Canada.
[Jovin, Tudor G.] Univ Pittsburgh, Med Ctr, Stroke Inst, Pittsburgh, PA USA.
[Yan, Bernard] Univ Melbourne, Royal Melbourne Hosp, Melbourne Brain Ctr, Melbourne, Vic 3050, Australia.
[Silver, Frank L.] Univ Toronto, Dept Med, Div Neurol, Toronto, ON, Canada.
[Silver, Frank L.] Univ Hlth Network, Toronto, ON, Canada.
[von Kummer, Ruediger] Dresden Univ, Stroke Ctr, Univ Hosp, Dept Neuroradiol, Dresden, Germany.
[Molina, Carlos A.] Hosp Univ Vall dHebron, Dept Neurol, Neurovasc Unit, Barcelona, Spain.
[Demaerschalk, Bart M.] Mayo Clin, Dept Neurol, Phoenix, AZ USA.
[Budzik, Ronald] Riverside Methodist Hosp, OhioHlth Neurosci Inst, Columbus, OH 43214 USA.
[Clark, Wayne M.] Oregon Hlth & Sci Univ, Oregon Stroke Ctr, Portland, OR 97201 USA.
[Zaidat, Osama O.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA.
[Malisch, Tim W.] Alexian Bros Med Ctr, Elk Grove Village, IL USA.
[Schonewille, Wouter J.] Univ Med Ctr Utrecht, Dept Neurol, Utrecht, Netherlands.
[Schonewille, Wouter J.] St Antonius Hosp, Nieuwegein, Netherlands.
[Mazighi, Mikael] Hop Xavier Bichat, Dept Neurol, Paris, France.
[Mazighi, Mikael] Hop Xavier Bichat, Stroke Ctr, Paris, France.
[Engelter, Stefan T.] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland.
[Anderson, Craig] Univ Sydney, Royal Prince Alfred Hosp, George Inst Global Hlth, Sydney, NSW 2006, Australia.
[Janis, L. Scott] NINDS, NIH, Bethesda, MD 20892 USA.
RP Broderick, JP (reprint author), Univ Cincinnati, Dept Neurol, Inst Neurosci, 260 Stetson St,Suite 2300,POB 670525, Cincinnati, OH 45267 USA.
EM joseph.broderick@uc.edu
RI Demchuk, Andrew/E-1103-2012;
OI Demchuk, Andrew/0000-0002-4930-7789; Yan, Bernard/0000-0001-8802-9606;
Hill, Michael/0000-0002-6269-1543
FU National Institutes of Health; National Institute of Neurological
Disorders and Stroke [UC U01NS052220, MUSC U01NS054630, U01NS077304];
Genentech; EKOS; Concentric Medical; Cordis Neurovascular; Boehringer
Ingelheim; Oakstone Publishing; BrainsGate; Edge Therapeutics; Covidien;
Penumbra; Janssen Pharmaceuticals; Medical Dialogues; Vernalis Group;
Hoffmann-La Roche Canada; Servier Canada; Bristol-Myers Squibb Canada;
Heart and Stroke Foundation of Alberta, Northwest Territories, and
Nunavut; Alberta Innovates-Health Solutions; Silk Road Medical;
Boehringer Ingelheim Canada; Lundbeck; GE Healthcare; Photo-Thera
FX Funded by the National Institutes of Health and others;
ClinicalTrials.gov number, NCT00359424.); Supported by grants from the
National Institutes of Health and the National Institute of Neurological
Disorders and Stroke (UC U01NS052220, MUSC U01NS054630, and U01NS077304)
and by Genentech, EKOS, Concentric Medical, Cordis Neurovascular, and
Boehringer Ingelheim.; Dr. Broderick reports receiving consulting fees
from Photo-Thera, receiving lecture fees from Oakstone Publishing, and
receiving a drug from Schering-Plough for use in a study funded by the
National Institutes of Health. Dr. Palesch reports receiving consulting
fees from BrainsGate and Edge Therapeutics. Dr. Demchuk reports
receiving grant support and lecture fees from Covidien. Dr. Khatri
reports receiving consulting fees from Penumbra, Genentech, and Janssen
Pharmaceuticals; providing expert testimony for Medico-Legal Consulting;
receiving lecture fees from Medical Dialogues; receiving royalties from
Informa, and receiving travel support from Genentech. Dr. Hill reports
receiving consulting fees from Vernalis Group; receiving grant support
from Hoffmann-La Roche Canada; receiving lecture fees from Hoffmann-La
Roche Canada, Servier Canada, and Bristol-Myers Squibb Canada; receiving
stock options from Calgary Scientific; receiving support from the Heart
and Stroke Foundation of Alberta, Northwest Territories, and Nunavut and
Alberta Innovates-Health Solutions; and serving as an unpaid board
member for the Heart and Stroke Foundation of Alberta, Northwest
Territories, and Nunavut and the Institute of Circulatory and
Respiratory Health of the Canadian Institutes of Health Research. Dr.
Jovin reports receiving consulting fees and stock options from Silk Road
Medical. Dr. Silver reports serving as an unpaid board member for
Boehringer Ingelheim Canada, Bayer Canada, and Bristol-Myers Squibb and
Pfizer Canada; receiving lecture fees from Boehringer Ingelheim Canada
and Servier Canada; and receiving travel support from Boehringer
Ingelheim Canada. Dr. von Kummer reports serving as a board member for
Lundbeck and Boehringer Ingelheim; receiving consulting fees from
Lundbeck; and receiving lecture fees from Penumbra, Boehringer
Ingelheim, and Lundbeck. Dr. Demaerschalk reports receiving grant
support and consultant fees from Genentech. Dr. Budzik reports receiving
consulting and lecture fees from Concentric Medical. Dr. Goyal reports
receiving consulting and lecture fees from Covidien; receiving grant
support from Covidien; and owning stock options in Calgary Scientific
and NoNO. Dr. Engelter reports serving as a board member for Boehringer
Ingelheim and receiving travel support from Boehringer Ingelheim. Dr.
Anderson reports receiving lecture fees and travel support from GE
Healthcare. Ms. Spilker reports receiving payment for the development of
educational presentations from The Stroke Group and serving as a board
member for The Stroke Interventionalist: The Clinical Journal of Acute
Stroke Treatment. Dr. Tomsick reports receiving grant support from
Covidien. No other potential conflict of interest relevant to this
article was reported.
NR 34
TC 779
Z9 804
U1 6
U2 55
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 MAR 7
PY 2013
VL 368
IS 10
BP 893
EP 903
DI 10.1056/NEJMoa1214300
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 100BG
UT WOS:000315669100005
PM 23390923
ER
PT J
AU Lee, C
Lamart, S
Moroz, BE
AF Lee, Choonsik
Lamart, Stephanie
Moroz, Brian E.
TI Computational lymphatic node models in pediatric and adult hybrid
phantoms for radiation dosimetry
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID HUMAN ANATOMY; FEMALE; SIZE; NUMBER; PROTECTION; CT
AB We developed models of lymphatic nodes for six pediatric and two adult hybrid computational phantoms to calculate the lymphatic node dose estimates from external and internal radiation exposures. We derived the number of lymphatic nodes from the recommendations in International Commission on Radiological Protection (ICRP) Publications 23 and 89 at 16 cluster locations for the lymphatic nodes: extrathoracic, cervical, thoracic (upper and lower), breast (left and right), mesentery (left and right), axillary (left and right), cubital (left and right), inguinal (left and right) and popliteal (left and right), for different ages (newborn, 1-, 5-, 10-, 15-year-old and adult). We modeled each lymphatic node within the voxel format of the hybrid phantoms by assuming that all nodes have identical size derived from published data except narrow cluster sites. The lymph nodes were generated by the following algorithm: (1) selection of the lymph node site among the 16 cluster sites; (2) random sampling of the location of the lymph node within a spherical space centered at the chosen cluster site; (3) creation of the sphere or ovoid of tissue representing the node based on lymphatic node characteristics defined in ICRP Publications 23 and 89. We created lymph nodes until the pre-defined number of lymphatic nodes at the selected cluster site was reached. This algorithm was applied to pediatric (newborn, 1-, 5-and 10-year-old male, and 15-year-old males) and adult male and female ICRP-compliant hybrid phantoms after voxelization. To assess the performance of our models for internal dosimetry, we calculated dose conversion coefficients, called S values, for selected organs and tissues with Iodine-131 distributed in six lymphatic node cluster sites using MCNPX2.6, a well validated Monte Carlo radiation transport code. Our analysis of the calculations indicates that the S values were significantly affected by the location of the lymph node clusters and that the values increased for smaller phantoms due to the shorter inter-organ distances compared to the bigger phantoms. By testing sensitivity of S values to random sampling and voxel resolution, we confirmed that the lymph node model is reasonably stable and consistent for different random samplings and voxel resolutions.
C1 [Lee, Choonsik; Lamart, Stephanie; Moroz, Brian E.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Lee, C (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM leechoonsik@mail.nih.gov
RI Lee, Choonsik/C-9023-2015
OI Lee, Choonsik/0000-0003-4289-9870
FU Intramural NIH HHS [ZIA CP010132-17]
NR 32
TC 4
Z9 5
U1 0
U2 6
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD MAR 7
PY 2013
VL 58
IS 5
BP N59
EP N82
DI 10.1088/0031-9155/58/5/N59
PG 24
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 093KS
UT WOS:000315191400002
PM 23391692
ER
PT J
AU Warner, ET
Glasgow, RE
Emmons, KM
Bennett, GG
Askew, S
Rosner, B
Colditz, GA
AF Warner, Erica T.
Glasgow, Russell E.
Emmons, Karen M.
Bennett, Gary G.
Askew, Sandy
Rosner, Bernard
Colditz, Graham A.
TI Recruitment and retention of participants in a pragmatic randomized
intervention trial at three community health clinics: Results and
lessons learned
SO BMC PUBLIC HEALTH
LA English
DT Article
DE Health disparities; Weight-loss; Obesity; Hypertension; Pragmatic trial;
Recruitment; Retention
ID TERM WEIGHT-LOSS; AFRICAN-AMERICANS; MEDICAL-RESEARCH; FOLLOW-UP;
OBESITY; PROGRAM; COHORT; WOMEN; HYPERTENSION; PREVALENCE
AB Background: Obesity and hypertension and their associated health complications disproportionately affect communities of color and people of lower socioeconomic status. Recruitment and retention of these populations in research trials, and retention in weight loss trials has been an ongoing challenge.
Methods: Be Fit, Be Well was a pragmatic randomized weight loss and hypertension management trial of patients attending one of three community health centers in Boston, Massachusetts. Participants were asked to complete follow-up assessments every 6-months for two years. We describe challenges encountered and strategies implemented to recruit and retain trial participants over the 24-month intervention. We also identify baseline participant characteristics associated with retention status. Retention strategies included financial incentives, contact between assessment visits, building relationships with health center primary care providers (PCPs) and staff, and putting participant convenience first.
Results: Active refusal rates were low with 130 of 2,631 patients refusing participation (4.9%). Of 474 eligible persons completing telephone screening, 365 (77.0%) completed their baseline visit and were randomized into the study. The study population was predominantly non-Hispanic Black (71.2%), female (68.5%) and reported annual household income of less than $35,000 (70.1%). Recruitment strategies included use of passive approval of potential participants by PCPs, use of part-time staff, and outsourcing calls to a call center. A total of 314 (86.0%) people completed the 24-month visit. Retention levels varied across study visits and intervention condition. Most participants completed three or more visits (69.6%), with 205 (56.2%) completing all four. At 24-months, lower retention was observed for males and the intervention condition. Retention strategies included building strong relationships with clinic staff, flexibility in overcoming participant barriers through use of taxi vouchers, night and weekend appointments, and keeping participants engaged via newsletters and social gatherings.
Conclusion: We were able to retain 86.0% of participants at 24-months. Recruitment and retention of high percentages of racial/ethnic minorities and lower income samples is possible with planning, coordination with a trusted community setting and staff (e.g. community health centers and RAs), adaptability and building strong relationships.
C1 [Warner, Erica T.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Warner, Erica T.; Emmons, Karen M.; Bennett, Gary G.] Dana Farber Canc Inst, Ctr Community Based Res, Div Populat Sci, Boston, MA 02115 USA.
[Warner, Erica T.; Rosner, Bernard] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Bennett, Gary G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA.
[Bennett, Gary G.; Askew, Sandy] Duke Univ, Duke Global Hlth Inst, Durham, NC USA.
[Rosner, Bernard] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Rosner, Bernard] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA.
RP Warner, ET (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM ewarner@hsph.harvard.edu
RI Colditz, Graham/A-3963-2009
OI Colditz, Graham/0000-0002-7307-0291
FU National Heart, Lung, and Blood Institute [U01-HL087071, K22CA126992,
K05CA124415-04, 5T32CA009001-36, 5R25GM055353-14]
FX This work was supported in part by grant U01-HL087071 from the National
Heart, Lung, and Blood Institute and grants K22CA126992 (Dr. Bennett),
K05CA124415-04 (Dr. Emmons), 5T32CA009001-36 (Dr. Warner), and
5R25GM055353-14 (Dr. Warner).
NR 36
TC 13
Z9 13
U1 3
U2 17
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD MAR 6
PY 2013
VL 13
AR 192
DI 10.1186/1471-2458-13-192
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 119UH
UT WOS:000317123500002
PM 23496916
ER
PT J
AU Lucassen, EA
Zhao, XC
Rother, KI
Mattingly, MS
Courville, AB
de Jonge, L
Csako, G
Cizza, G
AF Lucassen, Eliane A.
Zhao, Xiongce
Rother, Kristina I.
Mattingly, Megan S.
Courville, Amber B.
de Jonge, Lilian
Csako, Gyorgy
Cizza, Giovanni
CA Sleep Extension Study Grp
TI Evening Chronotype Is Associated with Changes in Eating Behavior, More
Sleep Apnea, and Increased Stress Hormones in Short Sleeping Obese
Individuals
SO PLOS ONE
LA English
DT Article
ID MORNINGNESS-EVENINGNESS; FOOD-INTAKE; FREQUENCY; VALIDATION; EPIDEMIC;
ADULTS; MORNINGNESS/EVENINGNESS; CONTRIBUTORS; POPULATION; METABOLISM
AB Background: Short sleep duration and decreased sleep quality are emerging risk factors for obesity and its associated morbidities. Chronotype, an attribute that reflects individual preferences in the timing of sleep and other behaviors, is a continuum from morningness to eveningness. The importance of chronotype in relation to obesity is mostly unknown. Evening types tend to have unhealthy eating habits and suffer from psychological problems more frequently than Morning types, thus we hypothesized that eveningness may affect health parameters in a cohort of obese individuals reporting sleeping less than 6.5 hours per night.
Methodology and Principal Findings: Baseline data from obese (BMI: 38.5+/-6.4 kg/m(2)) and short sleeping (5.8+/-0.8 h/night by actigraphy) participants (n = 119) of the Sleep Extension Study were analyzed (www.ClinicalTrials.gov, identifier NCT00261898). Assessments included the Horne and Ostberg Morningness-Eveningness questionnaire, a three-day dietary intake diary, a 14-day sleep diary, 14 days of actigraphy, and measurements of sleep apnea. Twenty-four hour urinary free cortisol, 24 h urinary norepinephrine and epinephrine levels, morning plasma ACTH and serum cortisol, fasting glucose and insulin, and lipid parameters were determined. Eveningness was associated with eating later in the day on both working and non-working days. Progression towards eveningness was associated with an increase in BMI, resting heart rate, food portion size, and a decrease in the number of eating occasions and HDL-cholesterol. Evening types had overtly higher 24 h urinary epinephrine and morning plasma ACTH levels, and higher morning resting heart rate than Morning types. In addition, Evening types more often had sleep apnea, independent of BMI or neck circumference.
Conclusions: Eveningness was associated with eating later and a tendency towards fewer and larger meals and lower HDL-cholesterol levels. In addition, Evening types had more sleep apnea and higher stress hormones. Thus, eveningness in obese, chronically sleep-deprived individuals compounds the cardiovascular risk associated with obesity.
C1 [Lucassen, Eliane A.; Courville, Amber B.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Zhao, Xiongce] NIDDK, Intramural Res Program, NIH, Bethesda, MD USA.
[Rother, Kristina I.] NIH, Sect Pediat Diabet & Metab, Bethesda, MD 20892 USA.
[Mattingly, Megan S.; de Jonge, Lilian; Cizza, Giovanni] NIDDK, Sect Neuroendocrinol Obes, NIH, Bethesda, MD 20892 USA.
[Csako, Gyorgy] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Cizza, G (reprint author), NIDDK, Sect Neuroendocrinol Obes, NIH, Bethesda, MD 20892 USA.
EM cizzag@intra.niddk.nih.gov
OI de Jonge, Lilian/0000-0001-5900-0695
FU National Institutes of Health, Intramural Research Program, National
Institute of Diabetes and Digestive and Kidney Diseases; Fulbright;
VSBfonds; Leiden University Fund
FX This study was supported by the National Institutes of Health,
Intramural Research Program, National Institute of Diabetes and
Digestive and Kidney Diseases. EAL received scholarships from Fulbright,
VSBfonds and the Leiden University Fund. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript. None of the authors had a conflict of
interest.
NR 49
TC 40
Z9 40
U1 1
U2 31
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 MAR 6
PY 2013
VL 8
IS 3
AR e56519
DI 10.1371/journal.pone.0056519
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117EP
UT WOS:000316936100004
PM 23483886
ER
PT J
AU Mikolas, P
Kollarova, J
Sebkova, K
Saudek, V
Yilma, P
Kostrouchova, M
Krause, MW
Kostrouch, Z
Kostrouchova, M
AF Mikolas, Pavol
Kollarova, Johana
Sebkova, Katerina
Saudek, Vladimir
Yilma, Petr
Kostrouchova, Marketa
Krause, Michael W.
Kostrouch, Zdenek
Kostrouchova, Marta
TI GEI-8, a Homologue of Vertebrate Nuclear Receptor Corepressor NCoR/SMRT,
Regulates Gonad Development and Neuronal Functions in Caenorhabditis
elegans
SO PLOS ONE
LA English
DT Article
ID HISTONE DEACETYLASE COMPLEXES; C-ELEGANS; HORMONE-RECEPTORS; MEDIATED
REPRESSION; NERVOUS-SYSTEM; PROTEIN; SMRT; GENE; PROGRESSION; EXPRESSION
AB NCoR and SMRT are two paralogous vertebrate proteins that function as corepressors with unliganded nuclear receptors. Although C. elegans has a large number of nuclear receptors, orthologues of the corepressors NCoR and SMRT have not unambiguously been identified in Drosophila or C. elegans. Here, we identify GEI-8 as the closest homologue of NCoR and SMRT in C. elegans and demonstrate that GEI-8 is expressed as at least two isoforms throughout development in multiple tissues, including neurons, muscle and intestinal cells. We demonstrate that a homozygous deletion within the gei-8 coding region, which is predicted to encode a truncated protein lacking the predicted NR domain, results in severe mutant phenotypes with developmental defects, slow movement and growth, arrested gonadogenesis and defects in cholinergic neurotransmission. Whole genome expression analysis by microarrays identified sets of de-regulated genes consistent with both the observed mutant phenotypes and a role of GEI-8 in regulating transcription. Interestingly, the upregulated transcripts included a predicted mitochondrial sulfide: quinine reductase encoded by Y9C9A.16. This locus also contains non-coding, 21-U RNAs of the piRNA class. Inhibition of the expression of the region coding for 21-U RNAs leads to irregular gonadogenesis in the homozygous gei-8 mutants, but not in an otherwise wild-type background, suggesting that GEI-8 may function in concert with the 21-U RNAs to regulate gonadogenesis. Our results confirm that GEI-8 is the orthologue of the vertebrate NCoR/SMRT corepressors and demonstrate important roles for this putative transcriptional corepressor in development and neuronal function.
C1 [Mikolas, Pavol; Sebkova, Katerina; Kostrouchova, Marta] Charles Univ Prague, Fac Med 1, Inst Cellular Biol & Pathol, Lab Mol Biol & Genet, Prague, Czech Republic.
[Kollarova, Johana; Saudek, Vladimir; Yilma, Petr; Kostrouchova, Marketa; Kostrouch, Zdenek] Charles Univ Prague, Fac Med 1, Inst Cellular Biol & Pathol, Lab Mol Pathol, Prague, Czech Republic.
[Krause, Michael W.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Kostrouchova, M (reprint author), Charles Univ Prague, Fac Med 1, Inst Cellular Biol & Pathol, Lab Mol Biol & Genet, Prague, Czech Republic.
EM marta.kostrouchova@lf1.cuni.cz
OI Krause, Michael/0000-0001-6127-3940
FU Czech Science Foundation [304/08/0970]; Ministry of Education, Youth and
Sports of the Czech Republic [0021620806]; Charles University in Prague
[SVV 2012 264514, 579612]; National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK) of the National Institutes of Health, USA
FX The work was supported by the following grants: grant 304/08/0970 from
the Czech Science Foundation (http://www.gacr.cz/international.htm),
grant 0021620806 from the Ministry of Education, Youth and Sports of the
Czech Republic (http://www.msmt.cz), Prvouk/1LF/1 and UNCE 204022 from
the Charles University in Prague ( http://www.cuni.cz). PM, JK and KS
were partially supported by the grant SVV 2012 264514 from the Charles
University in Prague (http:// www.cuni.cz). KS was partially supported
by the Grant 579612 from the Charles University in Prague. MWK is
supported by the Intramural Research Program of the National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National
Institutes of Health, USA (http://www2.niddk.nih.gov). 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 68
TC 4
Z9 8
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 6
PY 2013
VL 8
IS 3
AR e58462
DI 10.1371/journal.pone.0058462
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117EP
UT WOS:000316936100119
PM 23484030
ER
PT J
AU Miura, K
Deng, BB
Tullo, G
Diouf, A
Moretz, SE
Locke, E
Morin, M
Fay, MP
Long, CA
AF Miura, Kazutoyo
Deng, Bingbing
Tullo, Gregory
Diouf, Ababacar
Moretz, Samuel E.
Locke, Emily
Morin, Merribeth
Fay, Michael P.
Long, Carole A.
TI Qualification of Standard Membrane-Feeding Assay with Plasmodium
falciparum Malaria and Potential Improvements for Future Assays
SO PLOS ONE
LA English
DT Article
ID TRANSMISSION-BLOCKING IMMUNITY; GAMETOCYTE INFECTIVITY; VACCINE;
ANTIBODIES; AREA; MOSQUITOS; PFS25; PARASITEMIA; POPULATIONS; VALIDATION
AB Vaccines that interrupt malaria transmission are of increasing interest and a robust functional assay to measure this activity would promote their development by providing a biologically relevant means of evaluating potential vaccine candidates. Therefore, we aimed to qualify the standard membrane-feeding assay (SMFA). The assay measures the transmission-blocking activity of antibodies by feeding cultured P. falciparum gametocytes to Anopheles mosquitoes in the presence of the test antibodies and measuring subsequent mosquito infection. The International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline Q2(R1) details characteristics considered in assay validation. Of these characteristics, we decided to qualify the SMFA for Precision, Linearity, Range and Specificity. The transmission-blocking 4B7 monoclonal antibody was tested over 6 feeding experiments at several concentrations to determine four suitable concentrations that were tested in triplicate in the qualification experiments (3 additional feeds) to evaluate Precision, Linearity and Range. For Specificity, 4B7 was tested in the presence of normal mouse IgG. We determined intra-and inter-assay variability of % inhibition of mean oocyst intensity at each concentration of 4B7 (lower concentrations showed higher variability). We also showed that % inhibition was dependent on 4B7 concentration and the activity is specific to 4B7. Since obtaining empirical data is time-consuming, we generated a model using data from all 9 feeds and simulated the effects of different parameters on final readouts to improve the assay procedure and analytical methods for future studies. For example, we estimated the effect of number of mosquitoes dissected on variability of % inhibition, and simulated the relationship between % inhibition in oocyst intensity and % inhibition of prevalence of infected mosquitos at different mean oocysts in the control. SMFA is one of the few biological assays used in preclinical and early clinical development of transmission-blocking vaccines, and this study strongly supports its further development and application.
C1 [Miura, Kazutoyo; Deng, Bingbing; Tullo, Gregory; Diouf, Ababacar; Moretz, Samuel E.; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Locke, Emily; Morin, Merribeth] PATH Malaria Vaccine Initiat, Washington, DC USA.
[Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Miura, K (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
EM kmiura@niaid.nih.gov
OI Fay, Michael P./0000-0002-8643-9625
FU National Institute of Allergy and Infectious Diseases/National
Institutes of Health; PATH Malaria Vaccine Initiative
FX The study was supported by the intramural program of the National
Institute of Allergy and Infectious Diseases/National Institutes of
Health and by the PATH Malaria Vaccine Initiative. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 36
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Z9 29
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 MAR 6
PY 2013
VL 8
IS 3
AR e57909
DI 10.1371/journal.pone.0057909
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117EP
UT WOS:000316936100053
PM 23483940
ER
PT J
AU Mota-Miranda, ACA
Barreto, FK
Amarante, MFC
Batista, E
Monteiro-Cunha, JP
Farre, L
Galvao-Castro, B
Alcantara, LCJ
AF Mota-Miranda, Aline C. A.
Barreto, Fernanda K.
Amarante, Maria F. C.
Batista, Everton
Monteiro-Cunha, Joana P.
Farre, Lourdes
Galvao-Castro, Bernardo
Alcantara, Luiz C. J.
TI Molecular characterization of HTLV-1 gp46 glycoprotein from health
carriers and HAM/TSP infected individuals
SO VIROLOGY JOURNAL
LA English
DT Article
DE HTLV-1; HAM/TSP; Gp46; Mutation
ID LYMPHOTROPIC VIRUS TYPE-1; I-ASSOCIATED MYELOPATHY; TROPICAL SPASTIC
PARAPARESIS; PROVIRAL LOAD; VACCINE DESIGN; CELL; PROTEINS; SELECTION;
ENTRY; SITES
AB Background: Human T-cell Leukemia Virus type 1 (HTLV-1) is the etiological agent of tropical spastic paraparesis/ HTLV-associated myelopathy (HAM/TSP) that can be identified in around 0.25%-3.8% of the infected population. Disease progression can be monitored by the proviral load and may depend on genetic factors, however, it is not well understood why some HTLV-1 infected people develop the disease while others do not. The present study attempts to assess the molecular diversity of gp46 glycoprotein in HAM/TSP patients and Health Carrier (HC) individuals.
Methods: Blood samples were collected from 10 individuals, and DNA was extracted from PBMCs to measure the HTLV-1 proviral load. The gp46 coding sequences were amplified PCR, cloned and sequenced. The molecular characterization was performed using bioinformatics tools.
Results: The median HTLV-1 proviral load of HC (n = 5) and HAM/TSP (n = 5) patients was similar (average 316,227 copies/106 PBMCs). The gp46 molecular characterization of 146 clones (70 HC and 76 HAM/TSP) revealed an overall diversity, within HC and HAM/TSP clones, of 0.4% and 0.6%, respectively. Five frequent mutations were detected among groups (HAM/TSP and HC clone sequences). A single amino acid (aa) substitution (S35L) was exclusive for the HC group, and three gp46 substitutions (F14S, N42H, G72S) were exclusive for the HAM/TSP group. The remaining frequent mutation (V247I) was present in both groups (p = 0.0014). The in silico protein analysis revealed that the mutated alleles F14S and N42H represent more hydrophilic and flexible protein domains that are likely to be less antigenic. The Receptor Binding Domain is quite variable in the HAM/TSP group. Two other domains (aa 53-75 and 175-209) that contain multiple linear T-cell epitopes showed genetic diversity in both HAM/TSP and HC groups. Further analysis revealed 27 and 13 T-cell epitopes for class I HLA alleles and class II HLA alleles, when analyzing the entire gp46.
Conclusions: The most common gp46 mutations were not associated clinical status because they were found in only one individual, except for the V247I mutation, that was found at viral clones from HAM/TSP ad HC individuals. Because of this, we cannot associate any of the gp46 found mutations with the clinical profile.
C1 [Mota-Miranda, Aline C. A.; Barreto, Fernanda K.; Galvao-Castro, Bernardo; Alcantara, Luiz C. J.] Fiocruz MS, CPqGM, Fundacao Oswaldo Cruz, Ctr Pesquisa Goncalo Moniz, BR-40295001 Salvador, BA, Brazil.
[Mota-Miranda, Aline C. A.; Monteiro-Cunha, Joana P.; Galvao-Castro, Bernardo] Escola Bahiana Med & Saude Publ, Salvador, BA, Brazil.
[Mota-Miranda, Aline C. A.; Monteiro-Cunha, Joana P.] Univ Fed Bahia, Inst Ciencias Saude, Salvador, BA, Brazil.
[Batista, Everton; Farre, Lourdes] Fundacao Oswaldo Cruz, Ctr Pesquisa Goncalo Moniz, Lab Patol Expt, Salvador, BA, Brazil.
[Amarante, Maria F. C.] NCI, NIH, Bethesda, MD 20892 USA.
RP Alcantara, LCJ (reprint author), Fiocruz MS, CPqGM, Fundacao Oswaldo Cruz, Ctr Pesquisa Goncalo Moniz, Rua Waldemar Falcao 121, BR-40295001 Salvador, BA, Brazil.
EM lalcan@bahia.fiocruz.br
OI Farre, Lourdes/0000-0002-3168-1940
FU FAPESB; CNPq
FX We would like to thank the FAPESB and CNPq financial support.
NR 44
TC 1
Z9 1
U1 0
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-422X
J9 VIROL J
JI Virol. J.
PD MAR 6
PY 2013
VL 10
AR 75
DI 10.1186/1743-422X-10-75
PG 10
WC Virology
SC Virology
GA 108NL
UT WOS:000316300400001
PM 23510700
ER
PT J
AU Volkow, ND
Tomasi, D
Wang, GJ
Telang, F
Fowler, JS
Logan, J
Maynard, LJ
Wong, CT
AF Volkow, Nora D.
Tomasi, Dardo
Wang, Gene-Jack
Telang, Frank
Fowler, Joanna S.
Logan, Jean
Maynard, L. Jayne
Wong, Christopher T.
TI Predominance of D2 Receptors in Mediating Dopamine's Effects in Brain
Metabolism: Effects of Alcoholism
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; ORAL METHYLPHENIDATE; HUNTINGTONS-DISEASE;
F-18 FALLYPRIDE; COCAINE ABUSERS; MESSENGER-RNA; PET; HUMANS; RELEASE;
BINDING
AB Dopamine signals through D1-like and D2-like receptors, which can stimulate or inhibit, respectively, neuronal activity. Here we assessed the balance between D1 or D2 receptor signaling in the human brain and how it is affected in alcoholism. Using PET, we measured the relationship between changes in dopamine and brain glucose metabolism induced by methylphenidate in controls and alcoholics. We show that methylphenidate induced significant DA increases in striatum, amygdala, and medial orbitofrontal cortex, whereas it decreased metabolism in these brain regions. Methylphenidate-induced dopamine increases were greater in controls than in alcoholics, whereas methylphenidate-induced metabolic decreases were greater in alcoholics. For both groups, methylphenidate-induced dopamine increases were associated with decreases in regional brain metabolism, and the correlations were strongest in subthalamic nuclei, anterior cingulate, and medial orbitofrontal cortex. These correlations were more extensive and robust and the slopes steeper in alcoholics than in controls despite their attenuated dopamine responses to methylphenidate, which suggests an impaired modulation of dopamine signals in the brain of alcoholic subjects. These findings are consistent with a predominant inhibitory effect of dopamine in the human brain that is likely mediated by the prominence of dopamine D2/D3 receptors.
C1 [Volkow, Nora D.; Telang, Frank; Maynard, L. Jayne; Wong, Christopher T.] NIDA, Rockville, MD 20857 USA.
[Volkow, Nora D.; Tomasi, Dardo] NIAAA, Rockville, MD 20857 USA.
[Wang, Gene-Jack; Fowler, Joanna S.; Logan, Jean] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Wang, Gene-Jack; Fowler, Joanna S.; Logan, Jean] Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA.
RP Volkow, ND (reprint author), NIDA, Execut Blvd 6001,Room 5274, Rockville, MD 20857 USA.
EM nvolkow@nida.nih.gov
RI Tomasi, Dardo/J-2127-2015;
OI Logan, Jean/0000-0002-6993-9994
FU National Institutes of Health
FX This research was supported by the National Institutes of Health
intramural program.
NR 56
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Z9 10
U1 0
U2 8
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 6
PY 2013
VL 33
IS 10
BP 4527
EP 4535
DI 10.1523/JNEUROSCI.5261-12.2013
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 103OB
UT WOS:000315926300030
PM 23467368
ER
PT J
AU Varmus, H
Kumar, HS
AF Varmus, Harold
Kumar, Harpal S.
TI Addressing the Growing International Challenge of Cancer: A
Multinational Perspective
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID VACCINATION; COUNTRIES; MORTALITY; BENEFITS; BURDEN; DEATH
AB Leaders in cancer research and policy from 15 economically diverse countries met at the U.S. National Institutes of Health in November 2012 to discuss opportunities to reduce cancer incidence and mortality, improve cancer care, and increase our understanding of disease pathophysiology. Here, we present recommendations that the participants believe will enable faster progress in addressing the growing international challenge of cancer.
C1 [Varmus, Harold] NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Kumar, Harpal S.] Canc Res UK, London EC1V 4AD, England.
RP Varmus, H (reprint author), NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM harold.varmus@nih.gov; harpal.kumar@cancer.org.uk
NR 26
TC 12
Z9 14
U1 2
U2 6
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAR 6
PY 2013
VL 5
IS 175
AR 175cm2
DI 10.1126/scitranslmed.3005899
PG 5
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 103MY
UT WOS:000315922500001
PM 23467558
ER
PT J
AU Nishiyama, A
Sharov, AA
Piao, Y
Amano, M
Amano, T
Hoang, HG
Binder, BY
Tapnio, R
Bassey, U
Malinou, JN
Correa-Cerro, LS
Yu, H
Xin, L
Meyers, E
Zalzman, M
Nakatake, Y
Stagg, C
Sharova, L
Qian, Y
Dudekula, D
Sheer, S
Cadet, JS
Hirata, T
Yang, HT
Goldberg, I
Evans, MK
Longo, DL
Schlessinger, D
Ko, MSH
AF Nishiyama, Akira
Sharov, Alexei A.
Piao, Yulan
Amano, Misa
Amano, Tomokazu
Hoang, Hien G.
Binder, Bernard Y.
Tapnio, Richard
Bassey, Uwem
Malinou, Justin N.
Correa-Cerro, Lina S.
Yu, Hong
Xin, Li
Meyers, Emily
Zalzman, Michal
Nakatake, Yuhki
Stagg, Carole
Sharova, Lioudmila
Qian, Yong
Dudekula, Dawood
Sheer, Sarah
Cadet, Jean S.
Hirata, Tetsuya
Yang, Hsih-Te
Goldberg, Ilya
Evans, Michele K.
Longo, Dan L.
Schlessinger, David
Ko, Minoru S. H.
TI Systematic repression of transcription factors reveals limited patterns
of gene expression changes in ES cells
SO SCIENTIFIC REPORTS
LA English
DT Article
ID EMBRYONIC STEM-CELLS; SELF-RENEWAL; MICROARRAY DATA; PLURIPOTENCY;
NETWORK; CIRCUITRY; NANOG; DIFFERENTIATION; LINES; OCT4
AB Networks of transcription factors (TFs) are thought to determine and maintain the identity of cells. Here we systematically repressed each of 100 TFs with shRNA and carried out global gene expression profiling in mouse embryonic stem (ES) cells. Unexpectedly, only the repression of a handful of TFs significantly affected transcriptomes, which changed in two directions/trajectories: one trajectory by the repression of either Pou5f1 or Sox2; the other trajectory by the repression of either Esrrb, Sall4, Nanog, or Tcfap4. The data suggest that the trajectories of gene expression change are already preconfigured by the gene regulatory network and roughly correspond to extraembryonic and embryonic fates of cell differentiation, respectively. These data also indicate the robustness of the pluripotency gene network, as the transient repression of most TFs did not alter the transcriptomes.
C1 [Nishiyama, Akira; Sharov, Alexei A.; Piao, Yulan; Amano, Misa; Amano, Tomokazu; Hoang, Hien G.; Binder, Bernard Y.; Tapnio, Richard; Bassey, Uwem; Malinou, Justin N.; Correa-Cerro, Lina S.; Yu, Hong; Xin, Li; Meyers, Emily; Zalzman, Michal; Nakatake, Yuhki; Stagg, Carole; Sharova, Lioudmila; Qian, Yong; Dudekula, Dawood; Sheer, Sarah; Cadet, Jean S.; Hirata, Tetsuya; Yang, Hsih-Te; Goldberg, Ilya; Evans, Michele K.; Longo, Dan L.; Schlessinger, David; Ko, Minoru S. H.] NIA, NIH, Baltimore, MD 21224 USA.
[Nakatake, Yuhki; Ko, Minoru S. H.] Keio Univ, Sch Med, Sakaguchi Lab, Dept Syst Med, Tokyo 1608582, Japan.
RP Ko, MSH (reprint author), NIA, NIH, Baltimore, MD 21224 USA.
EM kom@z7.keio.jp
RI Ko, Minoru/B-7969-2009; Amano, Tomokazu/F-9720-2013; Nakatake,
Yuhki/K-5405-2013; Goldberg, Ilya/H-5307-2011;
OI Ko, Minoru/0000-0002-3530-3015; Goldberg, Ilya/0000-0001-8514-6110;
Dudekula, Dawood/0000-0002-4054-1827
FU Intramural Research Program of the NIH, National Institute on Aging
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging.
NR 27
TC 28
Z9 28
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD MAR 6
PY 2013
VL 3
AR 1390
DI 10.1038/srep01390
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 100JR
UT WOS:000315695900001
PM 23462645
ER
PT J
AU Chapman, JW
O'Callaghan, CJ
Hu, N
Ding, K
Yothers, GA
Catalano, PJ
Shi, Q
Gray, RG
O'Connell, MJ
Sargent, DJ
AF Chapman, J. W.
O'Callaghan, C. J.
Hu, N.
Ding, K.
Yothers, G. A.
Catalano, P. J.
Shi, Q.
Gray, R. G.
O'Connell, M. J.
Sargent, D. J.
CA ACCENT Collaborative Grp
TI Innovative estimation of survival using log-normal survival modelling on
ACCENT database
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE colon cancer; survival; log-normal; Cox; Kaplan-Meier; ACCENT database
ID INDIVIDUAL PATIENT DATA; 18 RANDOMIZED-TRIALS; COLORECTAL-CANCER;
COLON-CANCER; PROPORTIONAL-HAZARDS; BREAST-CANCER; CETUXIMAB; THERAPY
AB Background: The ACCENT database, with individual patient data for 20 898 patients from 18 colon cancer clinical trials, was used to support Food and Drug Administration (FDA) approval of 3-year disease-free survival as a surrogate for 5-year overall survival. We hypothesised substantive differences in survival estimation with log-normal modelling rather than standard Kaplan-Meier or Cox approaches.
Methods: Time to relapse, disease-free survival, and overall survival were estimated using Kaplan-Meier, Cox, and log-normal approaches for male subjects aged 60-65 years, with stage III colon cancer, treated with 5-fluorouracil-based chemotherapy regimens (with 5FU), or with surgery alone (without 5FU).
Results: Absolute differences between Cox and log-normal estimates with (without) 5FU varied by end point. The log-normal model had 5.8 (6.3)% higher estimated 3-year time to relapse than the Cox model; 4.8 (5.1)% higher 3-year disease-free survival; and 3.2 (2.2)% higher 5-year overall survival. Model checking indicated greater data support for the log-normal than the Cox model, with Cox and Kaplan Meier estimates being more similar. All three model types indicate consistent evidence of treatment benefit on both 3-year disease-free survival and 5-year overall survival; patients allocated to 5FU had 5.0-6.7% higher 3-year disease-free survival and 5.3-6.8% higher 5-year overall survival.
Conclusion: Substantive absolute differences between estimates of 3-year disease-free survival and 5-year overall survival with log-normal and Cox models were large enough to be clinically relevant, and warrant further consideration.
C1 [Chapman, J. W.; O'Callaghan, C. J.; Hu, N.; Ding, K.] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada.
[Yothers, G. A.] Univ Pittsburgh, NSABP Biostat Ctr, Pittsburgh, PA USA.
[Yothers, G. A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Catalano, P. J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Shi, Q.; Sargent, D. J.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
[Gray, R. G.] Univ Birmingham, Birmingham, W Midlands, England.
[Yothers, G. A.; O'Connell, M. J.] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
RP Chapman, JW (reprint author), Queens Univ, NCIC Clin Trials Grp, 10 Stuart St, Kingston, ON, Canada.
EM jchapman@ctg.queensu.ca
OI Sargent, Daniel/0000-0002-2684-4741; Yothers, Greg/0000-0002-7965-7333
FU Canadian Cancer Society Research Institute; NCCTG grant from the
National Cancer Institute at the National Institutes of Health
[CA25224]; Canadian National Sciences and Engineering Research Council;
Queen's University Department of Community Health and Epidemiology
FX This work was supported by a Canadian Cancer Society Research Institute
grant to the NCIC Clinical Trials Group (CTG) for NCIC CTG Faculty; the
ACCENT group is supported by the NCCTG grant from the National Cancer
Institute at the National Institutes of Health (Grant CA25224); and N Hu
was supported by a Canadian National Sciences and Engineering Research
Council grant to K Ding and by Queen's University Department of
Community Health and Epidemiology graduate student support.
NR 19
TC 3
Z9 4
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAR 5
PY 2013
VL 108
IS 4
BP 784
EP 790
DI 10.1038/bjc.2013.34
PG 7
WC Oncology
SC Oncology
GA 114XI
UT WOS:000316775900008
PM 23385733
ER
PT J
AU Naing, A
LoRusso, P
Fu, S
Hong, D
Chen, HX
Doyle, LA
Phan, AT
Habra, MA
Kurzrock, R
AF Naing, A.
LoRusso, P.
Fu, S.
Hong, D.
Chen, H. X.
Doyle, L. A.
Phan, A. T.
Habra, M. A.
Kurzrock, R.
TI Insulin growth factor receptor (IGF-1R) antibody cixutumumab combined
with the mTOR inhibitor temsirolimus in patients with metastatic
adrenocortical carcinoma
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE phase I clinical trials; IGF-1R pathway; mTOR pathway; adrenocortical
carcinoma; cixutumumab
ID ADRENAL-CORTICAL CARCINOMA; TUMORS; MITOTANE; CANCER; CELLS; AKT;
UPSTREAM; KINASE; TRIAL
AB Background: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy without an available effective systemic chemotherapy. Insulin growth factor 2 (IGF-2) overexpression leading to the activation of the IGF-1 receptor (IGF-1R)/mammalian target of rapamycin (mTOR) pathway is well described in ACC. Cixutumumab, a fully human IgG1 monoclonal antibody directed at IGF-1R was combined with temsirolimus on the basis of preclinical data.
Methods: Patients received cixutumumab, 3-6 mg kg(-1) intravenously (IV) weekly, and temsirolimus, 25-37.5 mg IV weekly (4-week cycles), with restaging after 8 weeks.
Results: Twenty-six patients were enrolled (13 (50%) men); median age, 47 years; median number of prior therapies, 4. Five patients previously received an IGF-1R inhibitor and one, temsirolimus. The most frequent toxicities, at least possibly drug related, were grade 1-2 thrombocytopenia (38%), mucositis (58%), hypercholesterolaemia (31%), hypertriglyceridemia (35%), and hyperglycaemia (31%). In all, 11 of 26 patients (42%) achieved stable disease (SD) >6 months (duration range = 6-21 months) with 3 of the 11 having received a prior IGF-1R inhibitor.
Conclusion: Cixutumumab combined with temsirolimus was well tolerated and >40% of patients achieved prolonged SD.
C1 [Naing, A.; Fu, S.; Hong, D.; Kurzrock, R.] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Phase Clin Trials Program 1, Houston, TX 77030 USA.
[LoRusso, P.] Wayne State Univ, Barbara Ann Karmanos Canc Inst, Res Adm, Detroit, MI 48201 USA.
[Chen, H. X.; Doyle, L. A.] NCI, Canc Therapy Evaluat Program, NIH, Rockville, MD 20852 USA.
[Phan, A. T.] Univ Texas MD Anderson Canc Ctr, Dept GI Med Oncol, Houston, TX 77030 USA.
[Habra, M. A.] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia, Houston, TX 77030 USA.
RP Naing, A (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Phase Clin Trials Program 1, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM anaing@mdanderson.org
FU [R21CA13763301A1]; [U01CA62461]; [U01CA62487]
FX We acknowledge Kristie Lawhorn, RN, for coordinating and data
collection, and Joann Aaron, MA, for scientific review of and editing
the paper. This study was supported by R21CA13763301A1 (AN), U01CA62461
(RK), and U01CA62487 (PL).
NR 27
TC 43
Z9 45
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAR 5
PY 2013
VL 108
IS 4
BP 826
EP 830
DI 10.1038/bjc.2013.46
PG 5
WC Oncology
SC Oncology
GA 114XI
UT WOS:000316775900013
PM 23412108
ER
PT J
AU Sirur, A
Best, RB
AF Sirur, Anshul
Best, Robert B.
TI Effects of Interactions with the GroEL Cavity on Protein Folding Rates
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID MOLECULAR CHAPERONES; MACROMOLECULAR STRUCTURE; ESCHERICHIA-COLI;
CONFINED SPACES; CAGE; SIMULATIONS; BINDING; LANDSCAPE; RHODANESE;
THERMODYNAMICS
AB Encapsulation of proteins in chaperonins is an important mechanism by which the cell prevents the accumulation of misfolded species in the cytosol. However, results from theory and simulation for repulsive cavities appear to be inconsistent with recent experimental results showing, if anything, a slowdown in folding rate for encapsulated Rhodanese. We study the folding of Rhodanese in GroEL, using coarse-grained molecular simulations of the complete system including chaperonin and substrate protein. We find that, by approximating the substrate:GroEL interactions as repulsive, we obtain a strong acceleration in rate of between one and two orders of magnitude; a similar result is obtained by representing the chaperonin as a simple spherical cavity. Remarkably, however, we find that using a carefully parameterized, sequence-based potential to capture specific residue-residue interactions between Rhodanese and the GroEL cavity walls induces a very strong reduction of the folding rates. The effect of the interactions is large enough to completely offset the effects of confinement, such that folding in some cases can be even slower than that of the unconfined protein. The origin of the slowdown appears to be stabilization-relative to repulsive confinement-of the unfolded state through binding to the cavity walls, rather than a reduction of the diffusion coefficient along the folding coordinate.
C1 [Sirur, Anshul; Best, Robert B.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
RP Best, RB (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM robertbe@helix.nih.gov
RI Best, Robert/H-7588-2016
OI Best, Robert/0000-0002-7893-3543
FU Biotechnology and Biological Sciences Research Council studentship;
Royal Society University Research Fellowship
FX A.S. was supported by a Biotechnology and Biological Sciences Research
Council studentship and R.B.B. was supported by a Royal Society
University Research Fellowship.
NR 58
TC 15
Z9 15
U1 1
U2 30
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD MAR 5
PY 2013
VL 104
IS 5
BP 1098
EP 1106
DI 10.1016/j.bpj.2013.01.034
PG 9
WC Biophysics
SC Biophysics
GA 101AY
UT WOS:000315748800019
PM 23473493
ER
PT J
AU Li, YJ
Periwal, V
AF Li, Yanjun
Periwal, Vipul
TI Synergy in Free Radical Generation is Blunted by High-Fat Diet Induced
Alterations in Skeletal Muscle Mitochondrial Metabolism
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID OXYGEN SPECIES GENERATION; BETA-CELL MITOCHONDRIA; INSULIN-RESISTANCE;
OXIDATIVE-PHOSPHORYLATION; ACID CYCLE; 3-NITROPROPIONIC ACID; UNCOUPLING
PROTEINS; COMPUTATIONAL MODEL; COMPLEX-II; MECHANISMS
AB Due to their role in cellular energetics and metabolism, skeletal muscle mitochondria appear to play a key role in the development of insulin resistance and type II diabetes. High-fat diet can induce higher levels of reactive oxygen species (ROS), evidenced by hydrogen peroxide (H2O2) emission from mitochondria, which may be causal for insulin resistance in skeletal muscle. The underlying mechanisms are unclear. Recent published data on single substrate (pyruvate, succinate, fat) metabolism in both normal diet (CON) and high-fat diet (HFD) states of skeletal muscle allowed us to develop an integrated mathematical model of skeletal muscle mitochondrial metabolism. Model simulations suggested that long-term HFD may affect specific metabolic reaction/pathways by altering enzyme activities. Our model allows us to predict oxygen consumption and ROS generation for any combination of substrates. In particular, we predict a synergy between (iso-membrane potential) combinations of pyruvate and fat in ROS production compared to the sum of ROS production with each substrate singly in both CON and HFD states. This synergy is blunted in the HFD state.
C1 [Li, Yanjun; Periwal, Vipul] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA.
RP Periwal, V (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA.
EM vipulp@mail.nih.gov
RI Periwal, Vipul/I-1728-2012
FU Intramural Research Program of the National Institutes of Health;
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, Bethesda, MD
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health, Bethesda,
MD.
NR 57
TC 2
Z9 2
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 MAR 5
PY 2013
VL 104
IS 5
BP 1127
EP 1141
DI 10.1016/j.bpj.2013.01.025
PG 15
WC Biophysics
SC Biophysics
GA 101AY
UT WOS:000315748800022
PM 23473496
ER
PT J
AU Wang, E
Kawaoka, S
Yu, M
Shi, JW
Ni, T
Yang, WJ
Zhu, J
Roeder, RG
Vakoc, CR
AF Wang, Eric
Kawaoka, Shinpei
Yu, Ming
Shi, Junwei
Ni, Ting
Yang, Wenjing
Zhu, Jun
Roeder, Robert G.
Vakoc, Christopher R.
TI Histone H2B ubiquitin ligase RNF20 is required for MLL-rearranged
leukemia
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE epigenetics; cancer
ID RNA-POLYMERASE-II; ACUTE MYELOID-LEUKEMIA; H3K79 METHYLATION;
TUMOR-SUPPRESSOR; HUMAN-CELLS; GENE; TRANSCRIPTION; MONOUBIQUITINATION;
LEUKEMOGENESIS; UBIQUITYLATION
AB Mixed-lineage leukemia (MLL) fusions are potent oncogenes that initiate aggressive forms of acute leukemia. As aberrant transcriptional regulators, MLL-fusion proteins alter gene expression in hematopoietic cells through interactions with the histone H3 lysine 79 (H3K79) methyltransferase DOT1L. Notably, interference with MLL-fusion cofactors like DOT1L is an emerging therapeutic strategy in this disease. Here, we identify the histone H2B E3 ubiquitin ligase ring finger protein 20 (RNF20) as an additional chromatin regulator that is necessary for MLL-fusion-mediated leukemo-genesis. Suppressing the expression of Rnf20 in diverse models of MLL-rearranged leukemia leads to inhibition of cell proliferation, under tissue culture conditions as well as in vivo. Rnf20 knockdown leads to reduced expression of MLL-fusion target genes, effects resembling Dot1l inhibition. Using ChIP-seq, we found that H2B ubiquitination is enriched in the body of MLL-fusion target genes, correlating with sites of H3K79 methylation and transcription elongation. Furthermore, Rnf20 is required to maintain local levels of H3K79 methylation by Dot1l at Hoxa9 and Meis1. These findings support a model whereby cotranscriptional recruitment of Rnf20 at MLL-fusion target genes leads to amplification of Dot1l-mediated H3K79 methylation, thereby rendering leukemia cells dependent on Rnf20 to maintain their oncogenic transcriptional program.
C1 [Wang, Eric; Kawaoka, Shinpei; Shi, Junwei; Vakoc, Christopher R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
[Yu, Ming; Roeder, Robert G.] Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10065 USA.
[Shi, Junwei] SUNY Stony Brook, Mol & Cellular Biol Program, Stony Brook, NY 11794 USA.
[Ni, Ting; Yang, Wenjing; Zhu, Jun] NHLBI, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Roeder, RG (reprint author), Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10065 USA.
EM roeder@rockefeller.edu; vakoc@cshl.edu
OI Vakoc, Christopher/0000-0002-1158-7180
FU Starr Cancer Foundation Grant [I4-A430]; Edward P. Evans Foundation;
Martin Sass Foundation; F. M. Kirby Foundation; Leukemia and Lymphoma
Society Specialized Center of Research (SCOR) Grant [7132-08];
Burroughs-Wellcome Career Awards for Medical Scientists award; National
Cancer Institute Cancer Center Support Grant Development Funds [CA45508]
FX We thank M. Taylor, E. Earl, and L. Bianco for support with mouse work;
F. Karginov for assistance with RNA-seq analysis; and G. Blobel and C.
Hammell for comments on the manuscript. This work was supported by Starr
Cancer Foundation Grant I4-A430 (to C.R.V. and R.G.R), and additional
funding was provided by the Edward P. Evans Foundation, the Martin Sass
Foundation, and the F. M. Kirby Foundation. R.G.R. was also supported by
Leukemia and Lymphoma Society Specialized Center of Research (SCOR)
Grant 7132-08. C.R.V. is also supported by a Burroughs-Wellcome Career
Awards for Medical Scientists award and National Cancer Institute Cancer
Center Support Grant Development Funds (Grant CA45508).
NR 50
TC 26
Z9 27
U1 0
U2 23
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 MAR 5
PY 2013
VL 110
IS 10
BP 3901
EP 3906
DI 10.1073/pnas.1301045110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109OH
UT WOS:000316377400054
PM 23412334
ER
PT J
AU Chiorazzi, M
Rui, LX
Yang, YD
Ceribelli, M
Tishbi, N
Maurer, CW
Ranuncolo, SM
Zhao, H
Xu, WH
Chan, WCC
Jaffe, ES
Gascoyne, RD
Campo, E
Rosenwald, A
Ott, G
Delabie, J
Rimsza, LM
Shaham, S
Staudt, LM
AF Chiorazzi, Michael
Rui, Lixin
Yang, Yandan
Ceribelli, Michele
Tishbi, Nima
Maurer, Carine W.
Ranuncolo, Stella M.
Zhao, Hong
Xu, Weihong
Chan, Wing-Chung C.
Jaffe, Elaine S.
Gascoyne, Randy D.
Campo, Elias
Rosenwald, Andreas
Ott, German
Delabie, Jan
Rimsza, Lisa M.
Shaham, Shai
Staudt, Louis M.
TI Related F-box proteins control cell death in Caenorhabditis elegans and
human lymphoma
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cancer; ubiquitin
ID PROTEASOME-DEPENDENT DEGRADATION; C-ELEGANS; SIGNALING PATHWAY; B-CELLS;
BCL-2; GENE; PHOSPHORYLATION; INDUCTION; APOPTOSIS; EXPRESSION
AB Cell death is a common metazoan cell fate, and its inactivation is central to human malignancy. In Caenorhabditis elegans, apoptotic cell death occurs via the activation of the caspase CED-3 following binding of the EGL-1/BH3-only protein to the antiapoptotic CED-9/BCL2 protein. Here we report a major alternative mechanism for caspase activation in vivo involving the F-box protein DRE-1. DRE-1 functions in parallel to EGL-1, requires CED-9 for activity, and binds to CED-9, suggesting that DRE-1 promotes apoptosis by inactivating CED-9. FBXO10, a human protein related to DRE-1, binds BCL2 and promotes its degradation, thereby initiating cell death. Moreover, some human diffuse large B-cell lymphomas have inactivating mutations in FBXO10 or express FBXO10 at low levels. Our results suggest that DRE-1/FBXO10 is a conserved regulator of apoptosis.
C1 [Chiorazzi, Michael; Tishbi, Nima; Maurer, Carine W.; Shaham, Shai] Rockefeller Univ, Lab Dev Genet, New York, NY 10065 USA.
[Rui, Lixin; Yang, Yandan; Ceribelli, Michele; Ranuncolo, Stella M.; Zhao, Hong; Xu, Weihong; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Chan, Wing-Chung C.] Univ Nebraska, Dept Pathol, Omaha, NE 68198 USA.
[Chan, Wing-Chung C.] Univ Nebraska, Dept Microbiol, Omaha, NE 68198 USA.
[Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[Campo, Elias] Univ Barcelona, Hosp Clin, E-08036 Barcelona, Spain.
[Rosenwald, Andreas] Univ Wurzburg, Dept Pathol, D-97080 Wurzburg, Germany.
[Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, D-70376 Stuttgart, Germany.
[Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany.
[Delabie, Jan] Oslo Univ Hosp, Pathol Clin, N-0424 Oslo, Norway.
[Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA.
[Rimsza, Lisa M.] SW Oncol Grp, Ann Arbor, MI 48106 USA.
RP Shaham, S (reprint author), Rockefeller Univ, Lab Dev Genet, New York, NY 10065 USA.
EM shaham@rockefeller.edu; lstaudt@mail.nih.gov
OI Campo, elias/0000-0001-9850-9793; Delabie, Jan/0000-0001-5023-0689;
Jaffe, Elaine/0000-0003-4632-0301
FU National Research Service [F30AG035484]; National Institutes of Health
(NIH)/National Institute on Aging (NIA); NIH [GM07739]; National Health
and Medical Research Council of Australia [R01HD042680, R01NS081490];
National Cancer Institute (NCI) Strategic Partnerships to Evaluate
Cancer Signatures [UO1-CA 114778]; Intramural Research Program of the
NIH; NCI; Center for Cancer Research
FX We thank members of the S. S. and L. M. S. laboratories for comments and
the Shohei Mitani for strain C05C8.6(tm3719). Some nematode strains used
were provided by the Caenorhabditis Genetics Center. This work was
supported by National Research Service Award F30AG035484 from the
National Institutes of Health (NIH)/National Institute on Aging (NIA)
(to M. Chiorazzi); NIH Medical Scientist Training Program Grant GM07739
(to M. Chiorazzi); a C. J. Martin Fellowship from the National Health
and Medical Research Council of Australia (to L.R.); NIH Grants
R01HD042680 and R01NS081490 (to S.S.); National Cancer Institute (NCI)
Strategic Partnerships to Evaluate Cancer Signatures Grant UO1-CA
114778; and the Intramural Research Program of the NIH, NCI, Center for
Cancer Research.
NR 34
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U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 5
PY 2013
VL 110
IS 10
BP 3943
EP 3948
DI 10.1073/pnas.1217271110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109OH
UT WOS:000316377400061
PM 23431138
ER
PT J
AU Welsbie, DS
Yang, ZY
Ge, Y
Mitchell, KL
Zhou, XR
Martin, SE
Berlinicke, CA
Hackler, L
Fuller, J
Fu, J
Cao, LH
Han, B
Auld, D
Xue, T
Hirai, S
Germain, L
Simard-Bisson, C
Blouin, R
Nguyen, JV
Davis, CHO
Enke, RA
Boye, SL
Merbs, SL
Marsh-Armstrong, N
Hauswirth, WW
DiAntonio, A
Nickells, RW
Inglese, J
Hanes, J
Yau, KW
Quigley, HA
Zack, DJ
AF Welsbie, Derek S.
Yang, Zhiyong
Ge, Yan
Mitchell, Katherine L.
Zhou, Xinrong
Martin, Scott E.
Berlinicke, Cynthia A.
Hackler, Laszlo, Jr.
Fuller, John
Fu, Jie
Cao, Li-hui
Han, Bing
Auld, Douglas
Xue, Tian
Hirai, Syu-ichi
Germain, Lucie
Simard-Bisson, Caroline
Blouin, Richard
Nguyen, Judy V.
Davis, Chung-ha O.
Enke, Raymond A.
Boye, Sanford L.
Merbs, Shannath L.
Marsh-Armstrong, Nicholas
Hauswirth, William W.
DiAntonio, Aaron
Nickells, Robert W.
Inglese, James
Hanes, Justin
Yau, King-Wai
Quigley, Harry A.
Zack, Donald J.
TI Functional genomic screening identifies dual leucine zipper kinase as a
key mediator of retinal ganglion cell death
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE neuroprotection; MAP3K12; drug discovery
ID INHIBITOR SELECTIVITY; AXONAL REGENERATION; MOUSE RETINA; IN-VIVO;
DEGENERATION; GLAUCOMA; PATHWAY; NEURONS; INJURY; ELECTROPORATION
AB Glaucoma, a major cause of blindness worldwide, is a neurodegenerative optic neuropathy in which vision loss is caused by loss of retinal ganglion cells (RGCs). To better define the pathways mediating RGC death and identify targets for the development of neuroprotective drugs, we developed a high-throughput RNA interference screen with primary RGCs and used it to screen the full mouse kinome. The screen identified dual leucine zipper kinase (DLK) as a key neuroprotective target in RGCs. In cultured RGCs, DLK signaling is both necessary and sufficient for cell death. DLK undergoes robust posttranscriptional up-regulation in response to axonal injury in vitro and in vivo. Using a conditional knockout approach, we confirmed that DLK is required for RGC JNK activation and cell death in a rodent model of optic neuropathy. In addition, tozasertib, a small molecule protein kinase inhibitor with activity against DLK, protects RGCs from cell death in rodent glaucoma and traumatic optic neuropathy models. Together, our results establish a previously undescribed drug/drug target combination in glaucoma, identify an early marker of RGC injury, and provide a starting point for the development of more specific neuroprotective DLK inhibitors for the treatment of glaucoma, non-glaucomatous forms of optic neuropathy, and perhaps other CNS neurodegenerations.
C1 [Welsbie, Derek S.; Yang, Zhiyong; Ge, Yan; Mitchell, Katherine L.; Zhou, Xinrong; Berlinicke, Cynthia A.; Hackler, Laszlo, Jr.; Fuller, John; Fu, Jie; Han, Bing; Enke, Raymond A.; Merbs, Shannath L.; Hanes, Justin; Yau, King-Wai; Quigley, Harry A.; Zack, Donald J.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA.
[Welsbie, Derek S.; Quigley, Harry A.; Zack, Donald J.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Glaucoma Ctr Excellence, Baltimore, MD 21287 USA.
[Ge, Yan] Minist Educ, Key Lab Pathobiol, Changchun 130000, Peoples R China.
[Zhou, Xinrong] Harbin Med Univ, Affiliated Hosp 2, Dept Ophthalmol, Harbin 150086, Heilongjiang, Peoples R China.
[Martin, Scott E.; Auld, Douglas; Inglese, James] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Fu, Jie; Han, Bing; Hanes, Justin] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Ctr Nanomed, Baltimore, MD 21231 USA.
[Cao, Li-hui; Xue, Tian; Nguyen, Judy V.; Marsh-Armstrong, Nicholas; Yau, King-Wai; Zack, Donald J.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
[Hirai, Syu-ichi] Wakayama Med Univ, Sch Med, Dept Biol, Wakayama 6410011, Japan.
[Germain, Lucie; Simard-Bisson, Caroline; Marsh-Armstrong, Nicholas] Univ Laval, Ctr Hosp Affilie Univ Quebec, Ctr Rech Fonds Rech Quebec Sante, Ctr Lab Organogenese Expt,Lab Organogenese Expt, Quebec City, PQ G1J 1Z4, Canada.
[Germain, Lucie; Simard-Bisson, Caroline] Univ Laval, Fac Med, Dept Chirurg, Quebec City, PQ G1J 1Z4, Canada.
[Blouin, Richard] Univ Sherbrooke, Fac Sci, Dept Biol, Sherbrooke, PQ J1K 2R1, Canada.
[Davis, Chung-ha O.] Kennedy Krieger Inst, Hugo W Moser Res Inst, Baltimore, MD 21205 USA.
[Boye, Sanford L.; Hauswirth, William W.] Univ Florida, Dept Ophthalmol, Gainesville, FL 32610 USA.
[DiAntonio, Aaron] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA.
[Nickells, Robert W.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA.
[Inglese, James] NHGRI, NIH, Bethesda, MD 20892 USA.
[Zack, Donald J.] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
[Zack, Donald J.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA.
[Zack, Donald J.] Inst Vis, F-75012 Paris, France.
RP Zack, DJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA.
EM dzack@jhmi.edu
OI Fuller, John/0000-0002-6587-146X; Zack, Don/0000-0002-7966-1973
FU National Eye Institute; NIH; American Health Assistance Foundation;
Glaucoma Research Foundation; Research to Prevent Blindness, Inc; Macula
Vision Research Foundation; Eldon Family Foundation; Vision for Children
FX We thank Noriko Esumi, Akrit Sodhi, Ted Dawson, and Valina Dawson for
reviewing the manuscript and/or scientific advice; Mary Ellen Pease and
Matthew Steinhart for help with the rat glaucoma experiment; and
Jiangxia Wang and John McGready for assistance with the statistics. This
study was supported, in part, by grants from the National Eye Institute;
NIH; the American Health Assistance Foundation; Glaucoma Research
Foundation; Research to Prevent Blindness, Inc.; the Macula Vision
Research Foundation; the Eldon Family Foundation; Vision for Children;
and generous gifts from the Guerrieri Family Foundation and from Mr. and
Mrs. Robert and Clarice Smith.
NR 51
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U1 1
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 MAR 5
PY 2013
VL 110
IS 10
BP 4045
EP 4050
DI 10.1073/pnas.1211284110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109OH
UT WOS:000316377400078
PM 23431148
ER
PT J
AU Liu, HS
Chefer, S
Lu, HB
Guillem, K
Rea, W
Kurup, P
Yang, YH
Peoples, L
Stein, EA
AF Liu, Hua-Shan
Chefer, Svetlana
Lu, Hanbing
Guillem, Karine
Rea, William
Kurup, Pradeep
Yang, Yihong
Peoples, Laura
Stein, Elliot A.
TI Dorsolateral caudate nucleus differentiates cocaine from natural
reward-associated contextual cues
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE context cues; neuroplasticity; drug addiction
ID SEEKING BEHAVIOR; ORBITOFRONTAL CORTEX; ACCUMBENS NEURONS; FUNCTIONAL
MRI; INSULAR CORTEX; NEURAL SYSTEMS; BASOLATERAL AMYGDALA; PREFRONTAL
CORTEX; EXTENDED AMYGDALA; DECISION-MAKING
AB Chronic drug administration induces neuroplastic changes within brain circuits regulating cognitive control and/or emotions. Following repeated pairings between drug intake and environmental cues, increased sensitivity to or salience of these contextual cues provoke conscious or unconscious craving and enhance susceptibility to relapse. To explore brain circuits participating in such experience-induced plasticity, we combined functional MRI with a preclinical drug vs. food self-administration (SA) withdrawal model. Specifically, two groups of rats were trained to associate odor cues with the availability of i.v. cocaine or oral sucrose, respectively. After 20 d of cocaine or sucrose SA followed by prolonged (30 d) forced abstinence, animals were presented with odor cues previously associated with or without (S+/S-) reinforcer (cocaine/sucrose) availability while undergoing functional MRI scans. ANOVA results demonstrate that a learning effect distinguishing S+ from S- was seen in the insula and nucleus accumbens, with the insula response reflecting the individual history of cocaine SA intake. A main effect of group, distinguishing cocaine from sucrose, was seen in the medial prefrontal cortex (infralimbic, prelimbic, and cingulate cortex) and dorsolateral striatum. Critically, only the dorsomedial striatum demonstrated a double dissociation between the two SA groups and learning (S+ vs. S-). These findings demonstrate altered cortico-limbic-striatal reward-related processing to learned, environment reward-associated contextual odor cues, which may serve as potential biomarkers for therapeutic interventions.
C1 [Liu, Hua-Shan; Chefer, Svetlana; Lu, Hanbing; Rea, William; Kurup, Pradeep; Yang, Yihong; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Liu, Hua-Shan] Univ Penn, Dept Neurol, Ctr Funct Neuroimaging, Philadelphia, PA 19104 USA.
[Chefer, Svetlana] NIAID, NIH, Frederick, MD 21072 USA.
[Guillem, Karine] Univ Bordeaux, Inst Malad Neurodegenerat, F-33076 Bordeaux, France.
[Guillem, Karine] Univ Bordeaux 2, Neurophysiol Lab, CNRS, F-33076 Bordeaux, France.
[Guillem, Karine; Peoples, Laura] Univ Penn, Sch Med, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Peoples, Laura] Drexel Univ, Coll Med, Dept Physiol & Pharmacol, Philadelphia, PA 19129 USA.
RP Stein, EA (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM estein@mail.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse
(NIDA), National Institutes of Health (NIH); NIH; Institute for
Translational Medicine and Therapeutics of the University of
Pennsylvania; National Center for Research Resources [UL155024134]
FX We thank Dr. Anna Rose Childress for her helpful comments and insights
on the study. This work was supported by the Intramural Research Program
of the National Institute on Drug Abuse (NIDA), National Institutes of
Health (NIH), and by an NIH Director's Bench-to-Bedside grant (to L.P.
and E.A.S.). The project was also partially supported by the Institute
for Translational Medicine and Therapeutics of the University of
Pennsylvania and National Center for Research Resources Grant
UL155024134.
NR 62
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U1 1
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 5
PY 2013
VL 110
IS 10
BP 4093
EP 4098
DI 10.1073/pnas.1207531110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109OH
UT WOS:000316377400086
PM 23431137
ER
PT J
AU Hong, JH
Yang, D
Shcheynikov, N
Ohana, E
Shin, DM
Muallem, S
AF Hong, Jeong Hee
Yang, Dongki
Shcheynikov, Nikolay
Ohana, Ehud
Shin, Dong Min
Muallem, Shmuel
TI Convergence of IRBIT, phosphatidylinositol (4,5) bisphosphate, and
WNK/SPAK kinases in regulation of the Na+-HCO3- cotransporters family
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID RECEPTOR-BINDING PROTEIN; HCO3-SALVAGE; ROBETTA SERVER; IP3 RECEPTOR;
TRANSPORTERS; PREDICTION; CALCIUM; CLONING; DOMAIN; PNBC1
AB Fluid and HCO3- secretion is a vital function of secretory epithelia, involving basolateral HCO3- entry through the Na+-HCO3- cotransporter (NBC) NBCe1-B, and luminal HCO3- exit mediated by cystic fibrosis transmembrane conductance regulator (CFTR) and solute carrier family 26 (SLC26) Cl-/HCO3- exchangers. HCO3- secretion is highly regulated, with the WNK/SPAK kinase pathway setting the resting state and the IRBIT/PP1 pathway setting the stimulated state. However, we know little about the relationships between the WNK/SPAK and IRBIT/PP1 sites in the regulation of the transporters. The first 85 N-terminal amino acids of NBCe1-B function as an auto-inhibitory domain. Here we have identified a positively charged module within NBCe1-B(37-65) that is conserved in NBCn1-A and all 20 members of the NBC superfamily except NBCe1-A. This module is required for the interaction and activation of NBCe1-B and NBCn1-A by IRBIT and their regulation by phosphatidylinositol 4,5-bisphosphate (PIP2). Activation of the transporters by IRBIT and PIP2 is nonadditive but complementary. Phosphorylation of Ser65 mediates regulation of NBCe1-B by SPAK, and phosphorylation of Thr49 is required for regulation by IRBIT and SPAK. Sequence searches using the NBCe1-B regulatory module as a template identified a homologous sequence in the CFTR R domain and Slc26a6 sulfat transporter and antisigma factor antagonist (STAS) domain. Accordingly, the R and STAS domains bind IRBIT, and the R domain is required for activation of CFTR by IRBIT. These findings reveal convergence of regulatory modalities in a conserved domain of the NBC that may be present in other HCO3- transporters and thus in the regulation of epithelial fluid and HCO3- secretion.
C1 [Hong, Jeong Hee; Shcheynikov, Nikolay; Ohana, Ehud; Muallem, Shmuel] Natl Inst Dent & Craniofacial Res, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Yang, Dongki] Gachon Univ Med & Sci, Dept Physiol, Grad Sch Med, Inchon 406799, South Korea.
[Shin, Dong Min] Yonsei Univ, Coll Dent, Brain Korea Project 21, Dept Oral Biol, Seoul 120752, South Korea.
RP Muallem, S (reprint author), Natl Inst Dent & Craniofacial Res, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
EM Shmuel.Muallem@nih.gov
FU National Institutes of Health, National Institute of Dental and Cranial
Research Intramural Research Program [Z1A-DE000735]; National Research
Foundation of Korea [NRF-2009-352-E00046]; Korean Government; National
Research Foundation of Korea's Basic Science Research Program; Ministry
of Education, Science and Technology [2012-0003965, 2012R1A2A1A01003487]
FX This work was funded by the National Institutes of Health, National
Institute of Dental and Cranial Research Intramural Research Program
(Grant Z1A-DE000735); the National Research Foundation of Korea (Grant
NRF-2009-352-E00046, funded by the Korean Government); and the National
Research Foundation of Korea's Basic Science Research Program funded by
the Ministry of Education, Science and Technology (Grants 2012-0003965
and 2012R1A2A1A01003487).
NR 26
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U1 0
U2 6
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 MAR 5
PY 2013
VL 110
IS 10
BP 4105
EP 4110
DI 10.1073/pnas.1221410110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109OH
UT WOS:000316377400088
PM 23431199
ER
PT J
AU Robinson, OJ
Overstreet, C
Charney, DR
Vytal, K
Grillon, C
AF Robinson, Oliver J.
Overstreet, Cassie
Charney, Danielle R.
Vytal, Katherine
Grillon, Christian
TI Stress increases aversive prediction error signal in the ventral
striatum
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE threat of shock; punishment; anxiety; face perception
ID PUNISHMENT PREDICTION; TRYPTOPHAN DEPLETION; MISMATCH NEGATIVITY; REWARD
PREDICTION; ANXIETY; THREAT; RESPONSES; HUMANS; ROLES; FEAR
AB From job interviews to the heat of battle, it is evident that people think and learn differently when stressed. In fact, learning under stress may have long-term consequences; stress facilitates aversive conditioning and associations learned during extreme stress may result in debilitating emotional responses in posttraumatic stress disorder. The mechanisms underpinning such stress-related associations, however, are unknown. Computational neuroscience has successfully characterized several mechanisms critical for associative learning under normative conditions. One such mechanism, the detection of a mismatch between expected and observed outcomes within the ventral striatum (i.e., "prediction errors"), is thought to be a critical precursor to the formation of new stimulus-outcome associations. An untested possibility, therefore, is that stress may affect learning via modulation of this mechanism. Here we combine a translational model of stress with a cognitive neuro-imaging paradigm to demonstrate that stress significantly increases ventral striatum aversive (but not appetitive) prediction error signal. This provides a unique account of the propensity to form threat-related associations under stress with direct implications for our understanding of both normal stress and stress-related disorders.
C1 [Robinson, Oliver J.; Overstreet, Cassie; Charney, Danielle R.; Vytal, Katherine; Grillon, Christian] NIMH, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
RP Robinson, OJ (reprint author), NIMH, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
EM oliver.j.robinson@gmail.com
OI Robinson, Oliver/0000-0002-3100-1132
FU Intramural Research Program of the National Institute of Mental Health
FX We thank Angie Wu for help with subject scheduling and support and
Stuart White for indispensable help setting up PE models. This research
was supported by the Intramural Research Program of the National
Institute of Mental Health.
NR 34
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U1 4
U2 22
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 MAR 5
PY 2013
VL 110
IS 10
BP 4129
EP 4133
DI 10.1073/pnas.1213923110
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109OH
UT WOS:000316377400092
PM 23401511
ER
PT J
AU Pavlova, O
Peterson, JH
Ieva, R
Bernstein, HD
AF Pavlova, Olga
Peterson, Janine H.
Ieva, Raffaele
Bernstein, Harris D.
TI Mechanistic link between beta barrel assembly and the initiation of
autotransporter secretion
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE membrane protein assembly; outer membrane proteins; protein
translocation
ID BACTERIAL AUTOTRANSPORTER; OUTER-MEMBRANE; ESCHERICHIA-COLI;
CRYSTAL-STRUCTURE; PROTEIN-TRANSPORT; VIRULENCE FACTOR; DOMAIN;
BIOGENESIS; TRANSLOCATION; ARCHITECTURE
AB Autotransporters are bacterial virulence factors that contain an N-terminal extracellular ("passenger") domain and a C-terminal beta barrel ("beta") domain that anchors the protein to the outer membrane. The beta domain is required for passenger domain secretion, but its exact role in autotransporter biogenesis is unclear. Here we describe insights into the function of the beta domain that emerged from an analysis of mutations in the Escherichia coli O157:H7 autotransporter EspP. We found that the G1066A and G1081D mutations slightly distort the structure of the beta domain and delay the initiation of passenger domain translocation. Site-specific photocrosslinking experiments revealed that the mutations slow the insertion of the beta domain into the outer membrane, but do not delay the binding of the beta domain to the factor that mediates the insertion reaction (the Bam complex). Our results demonstrate that the beta domain does not simply target the passenger domain to the outer membrane, but promotes translocation when it reaches a specific stage of assembly. Furthermore, our results provide evidence that the Bam complex catalyzes the membrane integration of beta barrel proteins in a multistep process that can be perturbed by minor structural defects in client proteins.
C1 [Pavlova, Olga; Peterson, Janine H.; Ieva, Raffaele; Bernstein, Harris D.] NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
RP Bernstein, HD (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
EM harris_bernstein@nih.gov
RI Ieva, Raffaele/J-9207-2014
OI Ieva, Raffaele/0000-0002-3405-0650
FU National Institute of Diabetes and Digestive and Kidney Diseases
Intramural Research Program
FX We thank Travis Barnard for helping to construct Fig. 1 and Yihong Ye
for providing valuable comments on the manuscript. This work was
supported by the National Institute of Diabetes and Digestive and Kidney
Diseases Intramural Research Program.
NR 41
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U1 0
U2 28
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 MAR 5
PY 2013
VL 110
IS 10
BP E938
EP E947
DI 10.1073/pnas.1219076110
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109OH
UT WOS:000316377400011
PM 23431155
ER
PT J
AU Doubeni, CA
Weinmann, S
Adams, K
Kamineni, A
Buist, DSM
Ash, AS
Rutter, CM
Doria-Rose, VP
Corley, DA
Greenlee, RT
Chubak, J
Williams, A
Kroll-Desrosiers, AR
Johnson, E
Webster, J
Richert-Boe, K
Levin, TR
Fletcher, RH
Weiss, NS
AF Doubeni, Chyke A.
Weinmann, Sheila
Adams, Kenneth
Kamineni, Aruna
Buist, Diana S. M.
Ash, Arlene S.
Rutter, Carolyn M.
Doria-Rose, V. Paul
Corley, Douglas A.
Greenlee, Robert T.
Chubak, Jessica
Williams, Andrew
Kroll-Desrosiers, Aimee R.
Johnson, Eric
Webster, Joseph
Richert-Boe, Kathryn
Levin, Theodore R.
Fletcher, Robert H.
Weiss, Noel S.
TI Screening Colonoscopy and Risk for Incident Late-Stage Colorectal Cancer
Diagnosis in Average-Risk Adults A Nested Case-Control Study
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID SERVICES TASK-FORCE; FECAL-OCCULT-BLOOD; RANDOMIZED CONTROLLED TRIAL;
NATIONAL-INSTITUTES; BETHESDA GUIDELINES; MORTALITY; HEALTH;
SIGMOIDOSCOPY; POPULATION; STATEMENT
AB Background: The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancer.
Objective: To examine the association between screening colonoscopy and risk for incident late-stage colorectal cancer (CRC).
Design: Nested case-control study.
Setting: Four U.S. health plans.
Patients: 1039 average-risk adults enrolled for at least 5 years in one of the health plans. Case patients were aged 55 to 85 years on their diagnosis date (reference date) of stage IIB or higher (late-stage) CRC during 2006 to 2008. One or 2 control patients were selected for each case patient, matched on birth year, sex, health plan, and prior enrollment duration.
Measurements: Receipt of CRC screening 3 months to 10 years before the reference date, ascertained through medical record audits. Case patients and control patients were compared on receipt of screening colonoscopy or sigmoidoscopy by using conditional logistic regression that accounted for health history, socioeconomic status, and other screening exposures.
Results: In analyses restricted to 471 eligible case patients and their 509 matched control patients, 13 case patients (2.8%) and 46 control patients (9.0%) had undergone screening colonoscopy, which corresponded to an adjusted odds ratio (AOR) of 0.29 (95% CI, 0.15 to 0.58) for any late-stage CRC, 0.36 (CI, 0.16 to 0.80) for right colon cancer, and 0.26 (CI, 0.06 to 1.11; P = 0.069) for left colon/rectum cancer. Ninety-two case patients (19.5%) and 173 control patients (34.0%) had screening sigmoidoscopy, corresponding to an AOR of 0.50 (CI, 0.36 to 0.70) overall, 0.79 (CI, 0.51 to 1.23) for right colon late-stage cancer, and 0.26 (CI, 0.14 to 0.48) for left colon cancer.
Limitation: The small number of screening colonoscopies affected the precision of the estimates.
Conclusion: Screening with colonoscopy in average-risk persons was associated with reduced risk for diagnosis of incident late-stage CRC, including right-sided colon cancer. For sigmoidoscopy, this association was seen for left CRC, but the association for right colon late-stage cancer was not statistically significant.
C1 Univ Penn, Philadelphia, PA 19104 USA.
Meyers Primary Care Inst, Reliant Med Grp, Worcester, MA USA.
Univ Massachusetts, Sch Med, Worcester, MA USA.
Kaiser Permanente Northwest, Portland, OR USA.
HealthPartners Hlth Syst, Minneapolis, MN USA.
Grp Hlth Res Inst, Seattle, WA USA.
Univ Washington, Seattle, WA 98195 USA.
NCI, NIH, Bethesda, MD 20892 USA.
Kaiser Permanente, Div Res, Oakland, CA USA.
Marshfield Clin Res Fdn, Marshfield, WI USA.
Kaiser Permanente, Honolulu, HI USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Doubeni, CA (reprint author), Univ Penn, Perelman Sch Med, Dept Family Med & Community Hlth, 3400 Spruce St,Gates 2, Philadelphia, PA 19104 USA.
EM chyke.doubeni@uphs.upenn.edu
OI Doubeni, Chyke/0000-0001-7495-0285; Doria-Rose,
Vincent/0000-0002-8802-5143
FU National Cancer Institute of the National Institutes of Health
[UC2CA148576]; National Institutes of Health [K01-CA127118,
K01-CA127118-S1, U01-CA151736]; Surveillance, Epidemiology and End
Results Program of the National Cancer Institute [N01-CN-67009,
N01-PC-35142]; State of Washington
FX Grant Support: By grant UC2CA148576 from the National Cancer Institute
of the National Institutes of Health. Additional support was provided to
Dr. Doubeni through awards K01-CA127118, K01-CA127118-S1, and
U01-CA151736, also from the National Institutes of Health. Data
collection on cancer incidence for this study was supported in part by
data infrastructure developed by the HMO Cancer Research Network at
participating sites. Group Health Research Institute's Cancer
Surveillance System is funded in part by contracts N01-CN-67009 and
N01-PC-35142 from the Surveillance, Epidemiology and End Results Program
of the National Cancer Institute, with additional support from the State
of Washington.
NR 35
TC 52
Z9 52
U1 0
U2 4
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 MAR 5
PY 2013
VL 158
IS 5
BP 312
EP +
DI 10.7326/0003-4819-158-5-201303050-00003
PN 1
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 105HP
UT WOS:000316057700002
PM 23460054
ER
PT J
AU Wickner, RB
Edskes, HK
Bateman, DA
Kelly, AC
Gorkovskiy, A
Dayani, Y
Zhou, A
AF Wickner, Reed B.
Edskes, Herman K.
Bateman, David A.
Kelly, Amy C.
Gorkovskiy, Anton
Dayani, Yaron
Zhou, Albert
TI Amyloids and Yeast Prion Biology
SO BIOCHEMISTRY
LA English
DT Article
ID HET-S PRION; BETA-SHEET STRUCTURE; SOLID-STATE NMR; TRANSMISSION
ELECTRON-MICROSCOPY; TRANSCRIPTIONAL REGULATOR SFP1; DISEASE-RELATED
PROTEIN; 2-MU-M CIRCLE PLASMID; SACCHAROMYCES-CEREVISIAE; PSI+ PRION;
BATTEN-DISEASE
AB The prions (infectious proteins) of Saccharomyces cerevisiae are proteins acting as genes, by templating their conformation from one molecule to another in analogy to DNA templating its sequence. Most yeast prions are amyloid forms of normally soluble proteins, and a single protein sequence can have any of several self-propagating forms (called prion strains or variants), analogous to the different possible alleles of a DNA gene. A central issue in prion biology is the structural basis of this conformational templating process. The in-register parallel beta sheet structure found for several infectious yeast prion amyloids naturally suggests an explanation for this conformational templating. While most prions are plainly diseases, the [Het-s] prion of Podospora anserina may be a functional amyloid, with important structural implications. Yeast prions are important models for human amyloid diseases in general, particularly because new evidence is showing infectious aspects of several human amyloidoses previously classified as prions. We also review studies of the roles of chaperones, aggregate-collecting proteins, and other cellular components using yeast that have led the way in improving the understanding of similar processes that must be operating in many human amyloidoses.
C1 [Wickner, Reed B.; Edskes, Herman K.; Bateman, David A.; Kelly, Amy C.; Gorkovskiy, Anton; Dayani, Yaron; Zhou, Albert] NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Wickner, RB (reprint author), NIH, Bldg 8,Room 225,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA.
EM wickner@helix.nih.gov
RI Gorkovskiy, Anton/J-8930-2016
OI Gorkovskiy, Anton/0000-0003-4811-2282
FU Intramural Program of the National Institute of Diabetes and Digestive
and Kidney Diseases
FX This work was supported by the Intramural Program of the National
Institute of Diabetes and Digestive and Kidney Diseases.
NR 187
TC 28
Z9 28
U1 1
U2 28
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAR 5
PY 2013
VL 52
IS 9
BP 1514
EP 1527
DI 10.1021/bi301686a
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 102KW
UT WOS:000315844500002
PM 23379365
ER
PT J
AU Lomash, S
Chittori, S
Brown, P
Mayer, ML
AF Lomash, Suvendu
Chittori, Sagar
Brown, Patrick
Mayer, Mark L.
TI Anions Mediate Ligand Binding in Adineta vaga Glutamate Receptor Ion
Channels
SO STRUCTURE
LA English
DT Article
ID CRYSTAL-STRUCTURES; KAINATE RECEPTORS; TERMINAL DOMAIN; AMPA;
DESENSITIZATION; SELECTIVITY; MECHANISMS; ASSOCIATION; MODULATION;
ACTIVATION
AB AvGluR1, a glutamate receptor ion channel from the primitive eukaryote Adineta vaga, is activated by alanine, cysteine, methionine, and phenylalanine, which produce lectin-sensitive desensitizing responses like those to glutamate, aspartate, and serine. AvGluR1 LBD crystal structures reveal an unusual scheme for binding dissimilar ligands that may be utilized by distantly related odorant/chemo-sensory receptors. Arginine residues in domain 2 coordinate the gamma-carboxyl group of glutamate, whereas in the alanine, methionine, and serine complexes a chloride ion acts as a surrogate ligand, replacing the gamma-carboxyl group. Removal of Cl- lowers affinity for these ligands but not for glutamate or aspartate nor for phenylalanine, which occludes the anion binding site and binds with low affinity. AvGluR1 LBD crystal structures and sedimentation analysis also provide insights into the evolutionary link between prokaryotic and eukaryotic iGluRs and reveal features unique to both classes, emphasizing the need for additional structure-based studies on iGluR-ligand interactions.
C1 [Lomash, Suvendu; Chittori, Sagar; Mayer, Mark L.] NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA.
[Brown, Patrick] NIBIB, NIH, DHHS, Bethesda, MD 20892 USA.
RP Mayer, ML (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA.
EM mayerm@mail.nih.gov
RI Mayer, Mark/H-5500-2013;
OI Chittori, Sagar/0000-0003-1417-6552
FU U.S. Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-31-109-Eng-38]; NICHD, NIH, DHHS
FX We thank Dr. E. Isacoff for the AvGluR1 cDNA, the Swartz lab (NINDS) for
oocytes, and Andi Balbo and Carla Glasser for technical assistance.
Synchrotron diffraction data was collected at the Southeast Regional
Collaborative Access Team (SER-CAT) 22-ID beamline at the Advanced
Photon Source (APS), Argonne National Laboratory. Use of 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. This work was
supported by the intramural research program of NICHD, NIH, DHHS.
NR 44
TC 6
Z9 6
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
J9 STRUCTURE
JI Structure
PD MAR 5
PY 2013
VL 21
IS 3
BP 414
EP 425
DI 10.1016/j.str.2013.01.006
PG 12
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 104ER
UT WOS:000315975100013
PM 23434404
ER
PT J
AU Brew, BJ
McLean, CA
Major, EO
AF Brew, Bruce J.
McLean, Catriona A.
Major, Eugene O.
TI Progressive multifocal leukoencephalopathy caused by BK virus?
SO MEDICAL JOURNAL OF AUSTRALIA
LA English
DT Editorial Material
ID DISEASE
C1 [Brew, Bruce J.] St Vincents Hosp, Dept Neurol, Sydney, NSW 2010, Australia.
[McLean, Catriona A.] Alfred Hosp, Dept Anat Pathol, Melbourne, Vic, Australia.
[Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA.
RP Brew, BJ (reprint author), St Vincents Hosp, Dept Neurol, Sydney, NSW 2010, Australia.
EM b.brew@unsw.edu.au
RI Brew, Bruce/J-6513-2012
NR 8
TC 0
Z9 0
U1 1
U2 2
PU AUSTRALASIAN MED PUBL CO LTD
PI PYRMONT
PA LEVEL 2, 26-32 PYRMONT BRIDGE RD, PYRMONT, NSW 2009, AUSTRALIA
SN 0025-729X
J9 MED J AUSTRALIA
JI Med. J. Aust.
PD MAR 4
PY 2013
VL 198
IS 4
BP 179
EP 180
DI 10.5694/mja12.11798
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 106PI
UT WOS:000316156600003
PM 23451948
ER
PT J
AU Vasilakis, N
Widen, S
da Rosa, APAT
Wood, TG
Walker, PJ
Holmes, EC
Tesh, RB
AF Vasilakis, Nikos
Widen, Steven
da Rosa, Amelia P. A. Travassos
Wood, Thomas G.
Walker, Peter J.
Holmes, Edward C.
Tesh, Robert B.
TI Malpais spring virus is a new species in the genus vesiculovirus
SO VIROLOGY JOURNAL
LA English
DT Article
DE Malpais spring virus (MSPV); Family rhabdoviridae; Genus vesiculovirus;
Genome sequence; Phylogeny
ID VESICULAR STOMATITIS-VIRUS; P-GENE; PHYLOGENIES; PROTEIN
AB Background: Malpais Spring virus (MSPV) is a mosquito-borne rhabdovirus that infects a variety of wild and feral ungulates in New Mexico, including horses and deer. Although, initial serologic tests and electron microscopy at the time of isolation nearly 25 years ago provided evidence that MSPV is a novel virus, possibly related to vesiculoviruses, the virus still has not been approved as a new species.
Findings: Use of the illumina platform allowed us to obtain the complete genome of MSPV. Analysis of the complete 11019 nt genome sequence of the prototype 85-488NM strain of MSPV indicates that it encodes the five common rhabdovirus structural proteins (N, P, M, G and L) with alternative ORFs (> 180 nt) in the N, M and G genes, including a 249 nt ORF in the G gene predicted to encode a 9.26 kDa highly basic transmembrane protein. Although antigenically very distant, phylogenetic analysis of the L gene indicates that MSPV is most closely related to Jurona virus, also isolated from mosquitoes in Brazil, as well as a number of other vesiculoviruses.
Conclusions: In sum, our analysis indicates MSPV should be classified as a member of the genus Vesiculovirus, family Rhabdoviridae. The complete genome sequence of MSPV will be helpful in the development of a reverse genetics system to study the unique aspects of this vesiculovirus in vivo and in vitro, and will assist development of specific diagnostic tests to study the epidemiology of MSPV infection.
C1 [Vasilakis, Nikos; da Rosa, Amelia P. A. Travassos; Tesh, Robert B.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA.
[Vasilakis, Nikos; da Rosa, Amelia P. A. Travassos; Tesh, Robert B.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
[Vasilakis, Nikos; Tesh, Robert B.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA.
[Vasilakis, Nikos; Tesh, Robert B.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA.
[Widen, Steven; Wood, Thomas G.] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA.
[Walker, Peter J.] CSIRO Anim Food & Hlth Sci, Australian Anim Hlth Lab, Geelong, Vic 3220, Australia.
[Holmes, Edward C.] Univ Sydney, Sydney Emerging Infect & Biosecur Inst, Sch Biol Sci, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Vasilakis, N (reprint author), Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA.
EM nivasila@utmb.edu
RI Walker, Peter/H-6059-2013;
OI Walker, Peter/0000-0003-1851-642X; Holmes, Edward/0000-0001-9596-3552
FU Department of Pathology start up funds; Institute for Human Infections
and Immunity, University of Texas Medical Branch, NIH
[HHSN272201000040I/HHSN27200004/D04]
FX This work is supported in part by the Department of Pathology start up
funds and a grant from the Institute for Human Infections and Immunity,
University of Texas Medical Branch (NV), NIH contract
HHSN272201000040I/HHSN27200004/D04 (RBT).
NR 13
TC 6
Z9 6
U1 0
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-422X
J9 VIROL J
JI Virol. J.
PD MAR 4
PY 2013
VL 10
AR 69
DI 10.1186/1743-422X-10-69
PG 5
WC Virology
SC Virology
GA 108MY
UT WOS:000316298900001
PM 23497016
ER
PT J
AU Gallagher, JJ
Zhang, XW
Hall, FS
Uhl, GR
Bearer, EL
Jacobs, RE
AF Gallagher, Joseph J.
Zhang, Xiaowei
Hall, F. Scott
Uhl, George R.
Bearer, Elaine L.
Jacobs, Russell E.
TI Altered Reward Circuitry in the Norepinephrine Transporter Knockout
Mouse
SO PLOS ONE
LA English
DT Article
ID MAGNETIC-RESONANCE-SPECTROSCOPY; TENSOR-BASED MORPHOMETRY; VIVO H-1-NMR
SPECTROSCOPY; MANGANESE-ENHANCED MRI; DOPAMINE-TRANSPORTER; IN-VIVO;
SEROTONIN TRANSPORTER; ALZHEIMERS-DISEASE; N-ACETYLASPARTATE;
EXTRACELLULAR DOPAMINE
AB Synaptic levels of the monoamine neurotransmitters dopamine, serotonin, and norepinephrine are modulated by their respective plasma membrane transporters, albeit with a few exceptions. Monoamine transporters remove monoamines from the synaptic cleft and thus influence the degree and duration of signaling. Abnormal concentrations of these neuronal transmitters are implicated in a number of neurological and psychiatric disorders, including addiction, depression, and attention deficit/hyperactivity disorder. This work concentrates on the norepinephrine transporter (NET), using a battery of in vivo magnetic resonance imaging techniques and histological correlates to probe the effects of genetic deletion of the norepinephrine transporter on brain metabolism, anatomy and functional connectivity. MRS recorded in the striatum of NET knockout mice indicated a lower concentration of NAA that correlates with histological observations of subtle dysmorphisms in the striatum and internal capsule. As with DAT and SERT knockout mice, we detected minimal structural alterations in NET knockout mice by tensor-based morphometric analysis. In contrast, longitudinal imaging after stereotaxic prefrontal cortical injection of manganese, an established neuronal circuitry tracer, revealed that the reward circuit in the NET knockout mouse is biased toward anterior portions of the brain. This is similar to previous results observed for the dopamine transporter (DAT) knockout mouse, but dissimilar from work with serotonin transporter (SERT) knockout mice where Mn2+ tracings extended to more posterior structures than in wildtype animals. These observations correlate with behavioral studies indicating that SERT knockout mice display anxiety-like phenotypes, while NET knockouts and to a lesser extent DAT knockout mice display antidepressant-like phenotypic features. Thus, the mainly anterior activity detected with manganese-enhanced MRI in the DAT and NET knockout mice is likely indicative of more robust connectivity in the frontal portion of the reward circuit of the DAT and NET knockout mice compared to the SERT knockout mice.
C1 [Gallagher, Joseph J.; Zhang, Xiaowei; Bearer, Elaine L.; Jacobs, Russell E.] CALTECH, Beckman Inst, Biol Imaging Ctr, Pasadena, CA 91125 USA.
[Bearer, Elaine L.] Univ New Mexico, Dept Pathol, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Hall, F. Scott; Uhl, George R.] NIDA, Mol Neurobiol Branch, Intramural Res Program, Baltimore, MD USA.
RP Jacobs, RE (reprint author), CALTECH, Beckman Inst, Biol Imaging Ctr, Pasadena, CA 91125 USA.
EM rjacobs@caltech.edu
RI Hall, Frank/C-3036-2013
OI Hall, Frank/0000-0002-0822-4063
FU Beckman Institute; NIH NINDS [NS062184]; NIMH [MH087660]; NIMGS
[P5OGM08273]; NIDA [R01DA18184]; National Institute on Drug Abuse;
Harvey Family endowment
FX The project was funded in part by the Beckman Institute, NIH NINDS
NS062184, NIMH MH087660, NIMGS P5OGM08273 (ELB), and NIDA R01DA18184
(REJ) and, in part, by the National Institute on Drug Abuse, Intramural
Research Program (GRU and FSH), and by the Harvey Family endowment
(ELB). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 117
TC 7
Z9 9
U1 1
U2 22
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 MAR 4
PY 2013
VL 8
IS 3
AR e57597
DI 10.1371/journal.pone.0057597
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099PY
UT WOS:000315634900030
PM 23469209
ER
PT J
AU Epstein-Lubow, G
Khachaturian, AS
Ryan, LM
Baumgart, M
AF Epstein-Lubow, Gary
Khachaturian, Ara S.
Ryan, Laurie M.
Baumgart, Matthew
TI THE NATIONAL ALZHEIMER'S PROJECT ACT AND THE NATIONAL PLAN TO ADDRESS
ALZHEIMER'S DISEASE: AN UPDATE AND FUTURE DIRECTIONS
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Khachaturian, Ara S.] Journal Alzheimers Assoc, Alzheimers & Dementia, Rockville, MD USA.
[Ryan, Laurie M.] NIA, Bethesda, MD 20892 USA.
[Baumgart, Matthew] Alzheimers Assoc, Chicago, IL USA.
[Epstein-Lubow, Gary] Brown Univ, Providence, RI 02912 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S36
EP S37
PG 4
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400049
ER
PT J
AU Evans, JD
Lavretsky, H
O'Hara, R
Gildengers, A
AF Evans, Jovier D.
Lavretsky, Helen
O'Hara, Ruth
Gildengers, Ariel
TI COGNITION AND MOOD DISORDER: IS THERE A CONNECTION TO NEURODEGENERATION
AND COGNITIVE DECLINE?
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Evans, Jovier D.] NIMH, Bethesda, MD 20892 USA.
[Lavretsky, Helen] Univ Calif Los Angeles, Los Angeles, CA USA.
[O'Hara, Ruth] Stanford Univ, Palo Alto, CA 94304 USA.
[Gildengers, Ariel] Univ Pittsburgh, Pittsburgh, PA USA.
RI Lavretsky, Helen/M-5711-2015
OI Lavretsky, Helen/0000-0001-9990-5085
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S8
EP S9
PG 4
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400007
ER
PT J
AU Kellner, CH
Liebman, LS
Nazarian, R
Knapp, RG
McCall, WV
Husain, MM
Petrides, G
Young, RC
Greenberg, RM
Weiner, RD
Prudic, J
Rudorfer, MV
Lisanby, SH
AF Kellner, Charles H.
Liebman, Lauren S.
Nazarian, Roya
Knapp, Rebecca G.
McCall, W. Vaughn
Husain, Mustafa M.
Petrides, Georgios
Young, Robert C.
Greenberg, Robert M.
Weiner, Richard D.
Prudic, Joan
Rudorfer, Matthew V.
Lisanby, Sarah H.
TI Efficacy of Right Unilateral Ultrabrief Pulse Electroconvulsive Therapy
(ECT): Data from Phase 1 of the PRIDE Study
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Kellner, Charles H.; Liebman, Lauren S.; Nazarian, Roya] Mt Sinai, New York, NY USA.
[Knapp, Rebecca G.] Med Univ S Carolina, Charleston, SC 29425 USA.
[McCall, W. Vaughn] Georgia Hlth Sci Univ, Augusta, GA USA.
[Husain, Mustafa M.] Univ Texas SW, Dallas, TX USA.
[Petrides, Georgios] Zucker Hillside Hosp, Glen Oaks, NY USA.
[Young, Robert C.] Cornell Univ, Weill Med Coll, White Plains, NY USA.
[Young, Robert C.] Lutheran Med Ctr, Brooklyn, NY USA.
[Weiner, Richard D.; Lisanby, Sarah H.] Duke Univ, Durham, NC USA.
[Prudic, Joan] Columbia Univ, New York, NY USA.
[Rudorfer, Matthew V.] NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S131
EP S131
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400145
ER
PT J
AU Niederehe, G
Gallagher-Thompson, DE
Cook, IA
Wittink, MN
AF Niederehe, George
Gallagher-Thompson, Dolores E.
Cook, Ian A.
Wittink, Marsha N.
TI PERSONALIZING TREATMENT FOR LATE-LIFE DEPRESSION: RESEARCH APPROACHES
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Niederehe, George] NIMH, Bethesda, MD 20892 USA.
[Gallagher-Thompson, Dolores E.] Stanford Univ, Stanford, CA 94305 USA.
[Cook, Ian A.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Wittink, Marsha N.] Univ Rochester, Rochester, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S27
EP S28
PG 4
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400036
ER
PT J
AU Smith, JC
Abdala, APL
Borgmann, A
Rybak, IA
Paton, JFR
AF Smith, Jeffrey C.
Abdala, Ana P.L.
Borgmann, Anke
Rybak, Ilya A.
Paton, Julian F.R.
TI Brainstem respiratory networks: building blocks and microcircuits
SO TRENDS IN NEUROSCIENCES
LA English
DT Review
DE breathing; brainstem; respiratory central pattern generator; breathing
disorders
ID PRE-BOTZINGER COMPLEX; CENTRAL HYPOVENTILATION SYNDROME; MOUSE
PREBOTZINGER COMPLEX; NONSPECIFIC CATION CURRENT; PERSISTENT SODIUM
CURRENT; CENTRAL PATTERN GENERATOR; RHYTHM GENERATION; RETROTRAPEZOID
NUCLEUS; IN-VITRO; SEROTONERGIC NEURONS
AB Breathing movements in mammals are driven by rhythmic neural activity generated within spatially and functionally organized brainstem neural circuits comprising the respiratory central pattern generator (CPG). This rhythmic activity provides homeostatic regulation of gases in blood and tissues and integrates breathing with other motor acts. We review new insights into the spatial-functional organization of key neural microcircuits of this CPG from recent multidisciplinary experimental and computational studies. The emerging view is that the microcircuit organization within the CPG allows the generation of multiple rhythmic breathing patterns and adaptive switching between them, depending on physiological or pathophysiological conditions. These insights open the possibility for site- and mechanism-specific interventions to treat various disorders of the neural control of breathing.
C1 NINDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
Univ Bristol, Bristol Heart Inst, Sch Physiol & Pharmacol, Bristol, Avon, England.
Drexel Univ, Coll Med, Dept Anat & Neurobiol, Philadelphia, PA 19104 USA.
RP Smith, JC (reprint author), NINDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
EM smithj2@heliz.nih.gov
RI Abdala, Ana Paula/G-9104-2014
OI Abdala, Ana Paula/0000-0001-6051-2591
FU Intramural NIH HHS; NHLBI NIH HHS [R33 HL087379]; NINDS NIH HHS [R01
NS057815, R01 NS069220]
NR 113
TC 84
Z9 85
U1 1
U2 34
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0166-2236
J9 TRENDS NEUROSCI
JI Trends Neurosci.
PD MAR
PY 2013
VL 36
IS 3
BP 152
EP 162
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 113ZY
UT WOS:000316710400006
PM 23254296
ER
PT J
AU Merino, JG
Latour, LL
Tso, A
Lee, KY
Kang, DW
Davis, LA
Lazar, RM
Horvath, KA
Corso, PJ
Warach, S
AF Merino, J. G.
Latour, L. L.
Tso, A.
Lee, K. Y.
Kang, D. W.
Davis, L. A.
Lazar, R. M.
Horvath, K. A.
Corso, P. J.
Warach, S.
TI Blood-Brain Barrier Disruption after Cardiac Surgery
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Article
ID BYPASS GRAFT-SURGERY; RECOVERY MR-IMAGES; CEREBROSPINAL-FLUID;
CARDIOPULMONARY BYPASS; MATRIX METALLOPROTEINASES; EXPERIMENTAL STROKE;
REPERFUSION INJURY; RAT-BRAIN; OFF-PUMP; ARTERY
AB To shed light on brain complications occurring after heart surgery, the authors assessed BBB disruption and DWI findings in half of their patients by imaging at 24 hours after surgery and 24-48 hours later. Additionally, postcontrast T1 images were obtained postoperatively at 2-4 days in the other half of the patients. Almost half the patients undergoing cardiac surgery had evidence of BBB abnormalities and three-quarters showed acute lesions on DWI after surgery. BBB disruption is more prevalent in the first 24 hours after surgery. These findings suggest that MR can be used as an imaging biomarker to assess therapies that may protect the BBB in patients undergoing heart surgery.
BACKGROUND AND PURPOSE: CNS complications are often seen after heart surgery, and postsurgical disruption of the BBB may play an etiologic role. The objective of this study was to determine the prevalence of MR imaging-detected BBB disruption (HARM) and DWI lesions after cardiac surgery.
MATERIALS AND METHODS: All patients had an MRI after cardiac surgery. For half the patients (group 1), we administered gadolinium 24 hours after surgery and obtained high-resolution DWI and FLAIR images 24-48 hours later. We administered gadolinium to the other half (group 2) at the time of the postoperative scan, 2-4 days after surgery. Two stroke neurologists evaluated the images.
RESULTS: Of the 19 patients we studied, none had clinical evidence of a stroke or delirium at the time of the gadolinium administration or the scan, but 9 patients (47%) had HARM (67% in group 1; 30% in group 2; P = .18) and 14 patients (74%) had DWI lesions (70% in group 1; 78% in group 2; P = 1.0). Not all patients with DWI lesions had HARM, and not all patients with HARM had DWI lesions (P = .56).
CONCLUSIONS: Almost half the patients undergoing cardiac surgery have evidence of HARM, and three-quarters have acute lesions on DWI after surgery. BBB disruption is more prevalent in the first 24 hours after surgery. These findings suggest that MR imaging can be used as an imaging biomarker to assess therapies that may protect the BBB in patients undergoing heart surgery.
C1 [Merino, J. G.; Latour, L. L.; Davis, L. A.; Warach, S.] NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA.
[Merino, J. G.; Horvath, K. A.] Johns Hopkins Community Phys, Bethesda, MD USA.
[Tso, A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Lee, K. Y.] Yonsei Univ, Coll Med, Dept Neurol, Seoul, South Korea.
[Kang, D. W.] Asan Med Ctr, Seoul, South Korea.
[Lazar, R. M.] Columbia Univ, Dept Neurol, Coll Phys & Surg, New York, NY USA.
[Horvath, K. A.] NHLBI, Bethesda, MD 20892 USA.
[Corso, P. J.] Washington Hosp Ctr, Dept Cardiac Surg, Washington, DC 20010 USA.
RP Merino, JG (reprint author), Suburban Hosp Stroke Program, 8600 Old Georgetown Rd, Bethesda, MD 20814 USA.
EM merinoj@ninds.nih.gov
OI Lee, Kyung-Yul/0000-0001-5585-7739; Merino, Jose/0000-0002-6676-0008
FU Division of Intramural Research of the National Institute of
Neurological Disorders and Stroke of the National Institutes of Health
FX This research was supported by the Division of Intramural Research of
the National Institute of Neurological Disorders and Stroke of the
National Institutes of Health.
NR 41
TC 16
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U1 1
U2 5
PU AMER SOC NEURORADIOLOGY
PI DENVILLE
PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA
SN 0195-6108
EI 1936-959X
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD MAR
PY 2013
VL 34
IS 3
BP 518
EP 523
DI 10.3174/ajnr.A3251
PG 6
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 291RN
UT WOS:000329846900013
PM 22918429
ER
PT J
AU Ferzli, M
Roberson, R
Kuddo, T
Abebe, D
Spong, CY
AF Ferzli, Myriam
Roberson, Robin
Kuddo, Thea
Abebe, Daniel
Spong, Catherine Y.
TI Prenatal Alcohol Exposure Alters Acute Phosphorylation of Cellular
Signaling Pathways
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Roberson, Robin; Kuddo, Thea; Abebe, Daniel; Spong, Catherine Y.] NICHD, UPDN, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 65A
EP 65A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100008
ER
PT J
AU Johnson, J
Hoffman, GE
Le, WW
Kurus, M
Usdin, K
AF Johnson, Joshua
Hoffman, Gloria E.
Le, Wei Wei
Kurus, Meltem
Usdin, Karen
TI Increased Immature Follicle Involution in the Fragile X Premutation
Mouse
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Johnson, Joshua; Kurus, Meltem] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, New Haven, CT USA.
[Hoffman, Gloria E.; Le, Wei Wei] Morgan State Univ, Dept Biol, Baltimore, MD 21239 USA.
[Usdin, Karen] NIDDK, LCMB Gene Express & Regulat Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 77A
EP 77A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100053
ER
PT J
AU Rosenblatt, KP
Nicolaides, KH
Romero, R
Bryant-Greenwood, PK
Syngelaki, A
Menon, R
Galen, RS
Evans, MI
AF Rosenblatt, Kevin P.
Nicolaides, Kypros H.
Romero, Roberto
Bryant-Greenwood, Peter K.
Syngelaki, Argyro
Menon, Ramkumar
Galen, Robert S.
Evans, Mark I.
TI Proteomic Derived Biomarker Panel for First Trimester Identification of
Patients at Risk for Pre-Term Delivery
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Rosenblatt, Kevin P.] Univ Texas Houston, IMM, Houston, TX USA.
[Nicolaides, Kypros H.; Syngelaki, Argyro] Fetal Med Fdn, Harris Birthright Ctr, London, England.
[Romero, Roberto] NICHD, Pregnancy Res Branch, Detroit, MI USA.
[Bryant-Greenwood, Peter K.] UTMB, Galveston, TX USA.
[Menon, Ramkumar] Univ Hawaii, Honolulu, HI 96822 USA.
[Galen, Robert S.] U Georgia Publ Hlth, Athens, GA USA.
[Evans, Mark I.] Comprehens Genet, Prenatal Diag, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 80A
EP 80A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100063
ER
PT J
AU Hill, MJ
Segars, JH
Kino, T
AF Hill, Micah J.
Segars, James H.
Kino, Tomoshige
TI CREB-Regulated Transcription Coactivator 2 (CRTC2) Is a Coregulator of
the Progesterone and Glucocorticoid Receptor
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Hill, Micah J.; Segars, James H.; Kino, Tomoshige] NIH, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 101A
EP 102A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100135
ER
PT J
AU Muneyyirci-Delale, O
Charles, C
Sinaii, N
Anopa, J
Dalloul, M
Stratton, P
AF Muneyyirci-Delale, Ozgul
Charles, Cassandra
Sinaii, Ninet
Anopa, Jenny
Dalloul, Mudar
Stratton, Pamela
TI Sustained Improvement in Endometriosis-Related Pelvic Pain with
Leuprolide or Norethindrone Treatment
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Muneyyirci-Delale, Ozgul; Charles, Cassandra; Anopa, Jenny; Dalloul, Mudar] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
[Muneyyirci-Delale, Ozgul] Kings Cty Hosp Ctr, Brooklyn, NY USA.
[Sinaii, Ninet] NIH Clin Ctr, Biostat & Clin Epidemiol Serv, Bethesda, MD USA.
[Stratton, Pamela] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 147A
EP 148A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100288
ER
PT J
AU Stratton, P
Sinaii, N
Khachikyan, I
Ortiz, R
Gemmill, J
Shah, J
AF Stratton, Pamela
Sinaii, Ninet
Khachikyan, Izabella
Ortiz, Robin
Gemmill, Julie
Shah, Jay
TI Interrelationship among Levator Spasm, Sensitization, Myofascial
Dysfunction, Anxiety and Depression in Patients with Endometriosis and
Chronic Pelvic Pain
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Stratton, Pamela; Khachikyan, Izabella; Gemmill, Julie] NICHD, PRAE, Bethesda, MD USA.
[Sinaii, Ninet] CC, BCES, Bethesda, MD USA.
[Ortiz, Robin; Shah, Jay] NIH, RM, CC, Bethesda, MD 20892 USA.
[Ortiz, Robin] Loyola SOM, Maywood, IL USA.
[Gemmill, Julie] NYCOM, Old Westbury, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 148A
EP 149A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100292
ER
PT J
AU Devine, K
Egbuniwe, M
Mumford, S
Armstrong, AY
AF Devine, Kate
Egbuniwe, Mary
Mumford, Sunni
Armstrong, Alicia Y.
TI Is Pre-ART Myomectomy Cost-Effective in Women with Intramural (IM)
Fibroids?
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Devine, Kate; Mumford, Sunni; Armstrong, Alicia Y.] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 150A
EP 150A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100296
ER
PT J
AU Fru, KN
Levy, G
Wesley, R
Neiman, L
Venkatesan, A
Armstrong, A
AF Fru, Karenne N.
Levy, Gary
Wesley, Robert
Neiman, Lynnette
Venkatesan, Aradhana
Armstrong, Alicia
TI Prolactin as a Biomarker for Tumor Burden and Response to UPA Therapy in
African American Women with Symptomatic Leiomyoma
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Fru, Karenne N.; Levy, Gary; Neiman, Lynnette; Armstrong, Alicia] Eunice Kennedy Shriver Natl Inst Child & Human De, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Wesley, Robert] NIH, Dept Biostat, Bethesda, MD 20892 USA.
[Venkatesan, Aradhana] NIH, Dept Radiol, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 150A
EP 150A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100297
ER
PT J
AU Levy, G
Malik, M
Britten, J
Segars, JH
Catherino, WH
AF Levy, Gary
Malik, Minnie
Britten, Joy
Segars, James H.
Catherino, William H.
TI Ulipristal Acetate Decreases TGF-beta 3 Expression and Dissolves
Extracellular Matrix in Leiomyoma Cells
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Levy, Gary; Malik, Minnie; Britten, Joy; Catherino, William H.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Levy, Gary; Segars, James H.; Catherino, William H.] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 151A
EP 151A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100300
ER
PT J
AU Zarek, SM
Driggers, PH
Malik, M
Segars, JH
AF Zarek, Shvetha M.
Driggers, Paul H.
Malik, Minnie
Segars, James H.
TI Characterization of AKAP13, Progesterone Receptor and Estrogen Receptor
Gene Expression in Breast Cancer Cells
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Zarek, Shvetha M.; Driggers, Paul H.; Malik, Minnie; Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Driggers, Paul H.; Segars, James H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 168A
EP 168A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100359
ER
PT J
AU Salafia, C
Girardi, T
Newschaffer, C
Miller, R
Walker, C
Misra, D
Katzman, P
Moye, J
Fallin, M
Herz-Picciotto, I
Croen, L
AF Salafia, C.
Girardi, T.
Newschaffer, C.
Miller, R.
Walker, C.
Misra, D.
Katzman, P.
Moye, J.
Fallin, M.
Herz-Picciotto, I.
Croen, L.
TI Placental Angiogenesis and ASD: Measurable Differences in Placental
Vascular Structure
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Salafia, C.] New York State Off Mental Retardat & Dev Disabil, Inst Basic Res, Staten Isl, NY USA.
[Girardi, T.] Placental Analyt, R&D, Larchmont, NY USA.
[Newschaffer, C.] Drexel Univ, Drexel Autism Ctr, Philadelphia, PA 19104 USA.
[Miller, R.] URSM, Rochester, NY USA.
[Walker, C.] UC Davis SOM, Sacramento, CA USA.
[Misra, D.] Wayne State Univ SOM, Detroit, MI USA.
[Katzman, P.] URSOM, Rochester, NY USA.
[Moye, J.] NICHD, Natl Childrens Study, Rockville, MD USA.
[Fallin, M.] JHU Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Herz-Picciotto, I.] UC, Sch Med, MIND Insitute, Sacramento, CA USA.
[Croen, L.] Kaiser Permanente, Res, Oakland, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 204A
EP 204A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100482
ER
PT J
AU Hill, MJ
Eltoukhi, H
Richter, KS
Widra, E
Wolff, EF
AF Hill, Micah J.
Eltoukhi, Heba
Richter, Kevin S.
Widra, Eric
Wolff, Erin F.
TI Endometrial Thickness on the Day of hCG Trigger Positively Correlates
with ART Outcomes and Differs by Racial Group
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Hill, Micah J.; Eltoukhi, Heba; Wolff, Erin F.] NIH, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA.
[Richter, Kevin S.; Widra, Eric] Shady Grove Reprod Sci Ctr, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
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PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 225A
EP 225A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100552
ER
PT J
AU McDonnold, MA
AF McDonnold, Mollie A.
TI Waist to Hip Ratio Versus BMI as Predictor of Obesity Related Pregnancy
Outcomes
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [McDonnold, Mollie A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
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PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 247A
EP 247A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100624
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PT J
AU Cantu, J
AF Cantu, Jessica
TI Lab Abnormalities in Pregnancy-Associated Hypertension: Frequency and
Impact on Pregnancy Outcomes
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Cantu, Jessica] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
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PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
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PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 260A
EP 260A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100669
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PT J
AU Myatt, L
AF Myatt, Leslie
TI Identification of Different Phenotypes of Preeclampsia by Clustering
Analysis of Biomarker Profiles
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CY MAR 20-23, 2013
CL Orlando, FL
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C1 [Myatt, Leslie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 266A
EP 266A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100691
ER
PT J
AU Myatt, L
AF Myatt, Leslie
TI Relationship of Inflammatory Biomarkers in Preeclampsia to BMI
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Myatt, Leslie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 266A
EP 267A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100692
ER
PT J
AU Cox, J
Egbuniwe, M
Levy, G
Armstrong, A
Drieling, J
Neiman, L
AF Cox, Jeris
Egbuniwe, Mary
Levy, Gary
Armstrong, Alicia
Drieling, Jennifer
Neiman, Lynnette
TI Ulipristal Acetate Does Not Predispose the Fallopian Tube Epithelium to
Neoplastic Changes.
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Cox, Jeris; Levy, Gary; Armstrong, Alicia; Neiman, Lynnette] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Egbuniwe, Mary] Mt Sinai Hosp, Dept Ob GYN, New York, NY 10029 USA.
[Drieling, Jennifer] NCI, Dept Pathol, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 271A
EP 271A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100709
ER
PT J
AU Yu, B
Haymes, S
Zhou, YL
Levy, G
Segars, J
Armstrong, A
AF Yu, Bo
Haymes, Snezana
Zhou, Yaling
Levy, Gary
Segars, James
Armstrong, Alicia
TI Investigating the Role of Apoptosis in the Chemoprotection Effect of
GnRH Antagonist
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Yu, Bo; Levy, Gary; Segars, James; Armstrong, Alicia] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Haymes, Snezana; Zhou, Yaling] Walter Reed Natl Mil Med Ctr, Dept Res Programs, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 282A
EP 282A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100747
ER
PT J
AU Silver, R
AF Silver, Robert
CA Stillbirth Collaborative Res Netwo
TI 7-Dehydrocholesterol Reductase Gene Mutations and Stillbirth
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Silver, Robert] Univ Utah, Salt Lake City, UT USA.
[Stillbirth Collaborative Res Netwo] NICHD, Stillbirth Collaborat Res Network, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 284A
EP 285A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100756
ER
PT J
AU Bolnick, JM
Kilburn, BA
Diamond, MP
Jeelani, R
Armant, DR
AF Bolnick, Jay M.
Kilburn, Brian A.
Diamond, Michael P.
Jeelani, Roohi
Armant, D. Randall
TI Trophoblast Cells Obtained by Noninvasive Transcervical Sampling during
Early Pregnancy Have an Extravillous Phenotype.
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Bolnick, Jay M.; Kilburn, Brian A.; Diamond, Michael P.; Jeelani, Roohi; Armant, D. Randall] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Armant, D. Randall] Wayne State Univ, Detroit, MI USA.
[Armant, D. Randall] NICHD, Program Reprod & Adult Endocrinol, NIH, DHHS, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 300A
EP 301A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100812
ER
PT J
AU Bolnick, JM
Namo, R
Chiang, PJ
Kilburn, BA
Diamond, MP
Smith, SM
Armant, RD
AF Bolnick, Jay M.
Namo, Rita
Chiang, Po Jen
Kilburn, Brian A.
Diamond, Michael P.
Smith, Susan M.
Armant, Randall D.
TI Apoptosis of Alcohol-Exposed Human Placental Cytotrophoblast Cells
Occurs Downstream of Intracellular Calcium Signaling.
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Bolnick, Jay M.; Namo, Rita; Chiang, Po Jen; Kilburn, Brian A.; Diamond, Michael P.; Armant, Randall D.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Smith, Susan M.] Univ Wisconsin, Madison, WI USA.
[Armant, Randall D.] Wayne State Univ, Detroit, MI USA.
[Armant, Randall D.] NICHD, Program Reprod & Adult Endocrinol, NIH, DHHS, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 301A
EP 301A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100813
ER
PT J
AU Myatt, L
AF Myatt, Leslie
TI Association of Maternal Biomarkers with Obstetric Outcomes.
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
CT 60th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation (SGI)
CY MAR 20-23, 2013
CL Orlando, FL
SP Soc Gynecol Invest
C1 [Myatt, Leslie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2013
VL 20
IS S3
SU 3
BP 330A
EP 330A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 287LK
UT WOS:000329543100912
ER
PT J
AU Boyington, JEA
Czajkowski, S
AF Boyington, Josephine E. A.
Czajkowski, Susan
TI Enrollment and Retention Challenges in Early-Phase Intervention
Development Studies: The Obesity-Related Behavioral Intervention Trials
(ORBIT)
SO PREVENTING CHRONIC DISEASE
LA English
DT Editorial Material
ID US ADULTS; PREVALENCE; TRENDS
C1 [Boyington, Josephine E. A.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Boyington, JEA (reprint author), NHLBI, NIH, 6701 Rockledge Dr,Ste 10224, Bethesda, MD 20892 USA.
EM boyingtonje@mail.nih.gov
NR 12
TC 0
Z9 0
U1 0
U2 1
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1545-1151
J9 PREV CHRONIC DIS
JI Prev. Chronic Dis.
PD MAR
PY 2013
VL 10
AR UNSP 130040
DI 10.5888/pcd10.130040
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 285JK
UT WOS:000329389800003
ER
PT J
AU Sutin, AR
Terracciano, A
Milaneschi, Y
An, Y
Ferrucci, L
Zonderman, AB
AF Sutin, Angelina R.
Terracciano, Antonio
Milaneschi, Yuri
An, Yang
Ferrucci, Luigi
Zonderman, Alan B.
TI The Effect of Birth Cohort on Well-Being: The Legacy of Economic Hard
Times
SO PSYCHOLOGICAL SCIENCE
LA English
DT Article
DE aging; well-being
ID LONGITUDINAL CHANGE; LIFE SATISFACTION; NEGATIVE AFFECT; UNITED-STATES;
AGE; HAPPINESS; PANEL
AB In the present research, we examined the effects of age, cohort, and time of measurement on well-being across adulthood. Cross-sectional and longitudinal analyses of two independent samples-one with more than 10,000 repeated assessments across 30 years (mean assessments per participant = 4.44, SD = 3.47) and one with nationally representative data-suggested that well-being declines with age. This decline, however, reversed when we controlled for birth cohort. That is, once we accounted for the fact that older cohorts had lower levels of well-being, all cohorts increased in well-being with age relative to their own baseline. Participants tested more recently had higher well-being, but time of measurement, unlike cohort, did not change the shape of the trajectory. Although well-being increased with age for everyone, cohorts that lived through the economic challenges of the early 20th century had lower well-being than those born during more prosperous times.
C1 [Sutin, Angelina R.; Terracciano, Antonio; Milaneschi, Yuri; An, Yang; Ferrucci, Luigi; Zonderman, Alan B.] NIA, Baltimore, MD 21224 USA.
[Sutin, Angelina R.; Terracciano, Antonio] Florida State Univ, Coll Med, Tallahassee, FL 32306 USA.
[Milaneschi, Yuri] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
RP Sutin, AR (reprint author), Florida State Univ, Coll Med, 1115 W Call St, Tallahassee, FL 32306 USA.
EM angelina.sutin@med.fsu.edu
RI terracciano, antonio/B-1884-2008;
OI Zonderman, Alan B/0000-0002-6523-4778
FU Intramural NIH HHS [Z99 AG999999, ZIA AG000183-22, ZIA AG000183-23]
NR 30
TC 14
Z9 14
U1 0
U2 22
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0956-7976
EI 1467-9280
J9 PSYCHOL SCI
JI Psychol. Sci.
PD MAR
PY 2013
VL 24
IS 3
BP 379
EP 385
DI 10.1177/0956797612459658
PG 7
WC Psychology, Multidisciplinary
SC Psychology
GA 113BN
UT WOS:000316640900019
PM 23349030
ER
PT J
AU de Mello, KGC
Mello, FCQ
Borga, L
Rolla, V
Duarte, RS
Sampaio, EP
Holland, SM
Prevots, DR
Dalcolmo, MP
AF Couto de Mello, Karla Gripp
Queiroz Mello, Fernanda C.
Borga, Liamar
Rolla, Valeria
Duarte, Rafael S.
Sampaio, Elizabeth P.
Holland, Steven M.
Prevots, D. Rebecca
Dalcolmo, Margareth P.
TI Clinical and Therapeutic Features of Pulmonary Nontuberculous
Mycobacterial Disease, Brazil, 1993-2011
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
ID KANSASII INFECTION; LUNG-DISEASE; EPIDEMIOLOGY; TUBERCULOSIS;
PREVALENCE; SYSTEMS
AB To identify clinical and therapeutic features of pulmonary nontuberculous mycobacterial (PNTM) disease, we conducted a retrospective analysis of patients referred to the Brazilian reference center, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, who received a diagnosis of PNTM during 1993-2011 with at least 1 respiratory culture positive for NTM. Associated conditions included bronchiectasis (21.8%), chronic obstructive pulmonary disease (20.7%), cardiovascular disease (15.5%), AIDS (9.8%), diabetes (9.8%), and hepatitis C (4.6%).Two patients had Hansen disease; 1 had Marfan syndrome. Four mycobacterial species comprised 85.6% of NTM infections: Mycobacterium kansasii, 59 cases (33.9%); M. avium complex, 53 (30.4%); M. abscessus, 23 (13.2%); and M. fortuitum, 14 (8.0%). A total of 42 (24.1%) cases were associated with rapidly growing mycobacteria. In countries with a high prevalence of tuberculosis, PNTM is likely misdiagnosed as tuberculosis, thus showing the need for improved capacity to diagnose mycobacterial disease as well as greater awareness of PNTM disease prevalence.
C1 [Couto de Mello, Karla Gripp; Borga, Liamar; Dalcolmo, Margareth P.] Fundacao Oswaldo Cruz, Natl Sch Publ Heath, Rio De Janeiro, Brazil.
[Queiroz Mello, Fernanda C.] Univ Fed Rio de Janeiro, Sch Med, Rio De Janeiro, Brazil.
[Rolla, Valeria; Sampaio, Elizabeth P.] Inst Oswaldo Cruz, BR-20001 Rio De Janeiro, Brazil.
[Duarte, Rafael S.] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil.
[Holland, Steven M.; Prevots, D. Rebecca] NIH, Bethesda, MD 20892 USA.
RP Dalcolmo, MP (reprint author), Estr Curicica 2000, BR-21045900 Curicica Rio de Janeiro, RJ, Brazil.
EM margarethdalcolmo@terra.com.br
FU Oswaldo Cruz Foundation; Division of Intramural Research of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, Maryland, USA; Conselho Nacional de Desenvolvimento
Cientifico e Tecnologico [303777/2010-9]; Fundacao de Amparo a Pesquisa
do Estado do Rio de Janeiro [E-26/111.497/2008, E-26/103.225/2011]
FX This study was supported in part by funds from the Oswaldo Cruz
Foundation and in part by the Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, Maryland, USA. F.C.Q.M. was supported by
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (project
no. 303777/2010-9) and by Fundacao de Amparo a Pesquisa do Estado do Rio
de Janeiro (project nos. E-26/111.497/2008 and E-26/103.225/2011).
NR 27
TC 14
Z9 14
U1 0
U2 4
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
EI 1080-6059
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD MAR
PY 2013
VL 19
IS 3
BP 393
EP 399
DI 10.3201/eid1903.120735
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 268LU
UT WOS:000328173000006
PM 23745217
ER
PT J
AU Bemmels, H
Biesecker, B
Schmidt, JL
Krokosky, A
Guidotti, R
Sutton, EJ
AF Bemmels, Heather
Biesecker, Barbara
Schmidt, Johanna L.
Krokosky, Alyson
Guidotti, Rick
Sutton, Erica J.
TI Psychological and Social Factors in Undergoing Reconstructive Surgery
Among Individuals With Craniofacial Conditions: An Exploratory Study
SO CLEFT PALATE-CRANIOFACIAL JOURNAL
LA English
DT Article
DE craniofacial conditions; decision making; parental role; pediatrics;
psychological and social implications; reconstructive surgery
ID TREACHER-COLLINS-SYNDROME; PORT-WINE STAINS; POSITIVE EXPOSURE; NOONAN
SYNDROME; CLEFT-LIP; CHILDREN; ADOLESCENTS; DIFFERENCE; MANAGEMENT;
ANOMALIES
AB Objective: Reconstructive surgery to improve psychological well-being is commonly offered to children with craniofacial conditions. Few studies have explored the challenges of reconstructive surgery beyond the physical risks: poor treatment outcomes, infection, brain damage, and death. This qualitative study aims to understand the psychological and social implications such interventions can have for individuals with craniofacial conditions.
Design: A total of 38 individuals between the ages of 12 and 61 with such craniofacial conditions as Sturge-Weber syndrome, Treacher Collins syndrome, Mobius syndrome, cleft lip and palate, Noonan syndrome, Crouzon syndrome, and amniotic band syndrome participated in semistructured video-recorded interviews. Participants were recruited at conferences, through study flyers, and by word of mouth. Descriptive, thematic analysis was used to identify themes related to reconstructive surgery.
Results: Dominant themes included undergoing surgery to reduce stigmatization, the psychological and social implications of the interventions, outcome satisfaction, parental involvement in decision making about surgery, and recommendations for parents considering surgery for their children with craniofacial conditions. Experiences with reconstructive surgery varied, with some participants expressing surgical benefits and others, disillusionment.
Conclusions: The range of participant attitudes and experiences reflect the complexity of reconstructive surgery. Pediatric health care teams involved in the care of children with craniofacial conditions play an important role in advising patients (and their parents) about existing treatment options. The psychological and social implications of reconstructive surgery should be relayed to help families weigh the risks and benefits of surgery in an informed and meaningful way.
C1 [Bemmels, Heather] Univ Minnesota, Dept Educ Psychol, Minneapolis, MN 55455 USA.
[Biesecker, Barbara] Johns Hopkins Univ, NHGRI, Genet Counseling Training Program, Bethesda, MD USA.
[Biesecker, Barbara] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Schmidt, Johanna L.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Krokosky, Alyson] Genet Alliance, Washington, DC USA.
[Guidotti, Rick] Posit Exposure, New York, NY USA.
[Sutton, Erica J.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5T 1P8, Canada.
[Sutton, Erica J.] Univ Toronto, Joint Ctr Bioeth, Toronto, ON M5T 1P8, Canada.
RP Sutton, EJ (reprint author), Univ Toronto, Dalla Lana Sch Publ Hlth, 155 Coll St,Suite 754, Toronto, ON M5T 1P8, Canada.
EM erica.sutton@utoronto.ca
OI Bemmels, Heather/0000-0003-4110-3906
FU Intramural Research Program at the National Human Genome Research
Institute, National Institutes of Health
FX This research was supported in part by the Intramural Research Program
at the National Human Genome Research Institute, National Institutes of
Health.
NR 36
TC 3
Z9 3
U1 2
U2 9
PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS
PI LAWRENCE
PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA
SN 1545-1569
EI 1055-6656
J9 CLEFT PALATE-CRAN J
JI Cleft Palate-Craniofac. J.
PD MAR
PY 2013
VL 50
IS 2
BP 158
EP 167
DI 10.1597/11-127
PG 10
WC Dentistry, Oral Surgery & Medicine; Surgery
SC Dentistry, Oral Surgery & Medicine; Surgery
GA 259NS
UT WOS:000327534200008
PM 22315960
ER
PT J
AU Banerjee, AA
Shen, H
Hautman, M
Anwer, J
Hong, S
Kapetanovic, IM
Liu, Y
Lyubimov, AV
AF Banerjee, Aryamitra A.
Shen, Hao
Hautman, Mathew
Anwer, Jaseem
Hong, Seungpyo
Kapetanovic, Izet M.
Liu, Ying
Lyubimov, Alexander V.
TI Enhanced Oral Bioavailability of The Hydrophobic Chemopreventive Agent
(Sr13668) in Beagle Dogs
SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY
LA English
DT Article
DE Polymeric nanoparticles; Bioavailability; Chemoprevention;
Nanoprecipitation; Oral drug delivery; Pharmacokinetics; Size
distribution; Surface charges
ID POLYMERIC NANOPARTICLES; FORMULATION; DELIVERY
AB Potency and activity of SR13668 in cancer prevention have been proven in several in vitro and in vivo cancer models. However, the compound is highly hydrophobic and its limited oral bioavailability has hindered its clinical translation. In this study, we encapsulated SR13668 into polymeric nanoparticles to increase compound aqueous solubility and therefore bioavailability. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (100-200nm) encapsulating SR13668 with narrow size distribution and high drug loading were generated by a continuous and scalable process of flash nanoprecipitation integrated with spray dry. A single gavage dose of SR13668-PLGA nanoparticles at 2.8 mg/kg was administered in eight beagle dogs. Drug levels in animal whole blood and plasma were measured over 24 hours. Enhanced bioavailability of SR13668 using nanoparticles compared with formulations of Labrasol (R) and neat drug in 0.5% methylcellulose is reported. This is the first attempt to study pharmacokinetics of SR13668 in large animals with orally administrated nanoparticle suspension.
C1 [Banerjee, Aryamitra A.; Lyubimov, Alexander V.] Univ Illinois, Toxicol Res Lab, Chicago, IL 60612 USA.
[Shen, Hao; Liu, Ying] Univ Illinois, Dept Chem Engn, Chicago, IL 60607 USA.
[Hautman, Mathew; Anwer, Jaseem] Ctr Biomed Testing, Chicago, IL 60612 USA.
[Hong, Seungpyo; Liu, Ying] Univ Illinois, Dept Biopharmaceut Sci, Chicago, IL 60612 USA.
[Kapetanovic, Izet M.] NCI, Bethesda, MD 20892 USA.
RP Lyubimov, AV (reprint author), Univ Illinois, Toxicol Res Lab, 808 S Wood St,Rm 1306, Chicago, IL 60612 USA.
EM liuying@uic.edu; lyubimov@uic.edu
FU National Cancer Institute, Department of Health and Human Services
[N01-CN-43306]
FX This study was financially supported by National Cancer Institute,
Department of Health and Human Services (contract number N01-CN-43306).
The authors are thankful to Dr. Yoon Yeo, Department of Industrial and
Physical Pharmacy and Weldon School of Biomedical Engineering at Purdue
University, for assisting us to use the spray drier in her laboratory
for preparing the nanoparticles.
NR 17
TC 3
Z9 3
U1 1
U2 10
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-2010
EI 1873-4316
J9 CURR PHARM BIOTECHNO
JI Curr. Pharm. Biotechnol.
PD MAR
PY 2013
VL 14
IS 4
BP 464
EP 469
PG 6
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 252DU
UT WOS:000326986000012
PM 23590143
ER
PT J
AU Peterson, EJR
Kireev, D
Moon, AF
Midon, M
Janzen, WP
Pingoud, A
Pedersen, LC
Singleton, SF
AF Peterson, Eliza J. R.
Kireev, Dmitri
Moon, Andrea F.
Midon, Marika
Janzen, William P.
Pingoud, Alfred
Pedersen, Lars C.
Singleton, Scott F.
TI Inhibitors of Streptococcus pneumoniae Surface Endonuclease EndA
Discovered by High-Throughput Screening Using a PicoGreen Fluorescence
Assay
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE Streptococcus pneumoniae; EndA; endonuclease; virulence factor;
high-throughput screening (HTS); PicoGreen
ID NEUTROPHIL EXTRACELLULAR TRAPS; GENETIC-TRANSFORMATION;
DIPLOCOCCUS-PNEUMONIAE; PROMISCUOUS INHIBITORS; NUCLEASE; ESCAPE; DNA;
DEOXYRIBONUCLEASE; EXPRESSION; MECHANISM
AB The human commensal pathogen Streptococcus pneumoniae expresses a number of virulence factors that promote serious pneumococcal diseases, resulting in significant morbidity and mortality worldwide. These virulence factors may give S. pneumoniae the capacity to escape immune defenses, resist antimicrobial agents, or a combination of both. Virulence factors also present possible points of therapeutic intervention. The activities of the surface endonuclease, EndA, allow S. pneumoniae to establish invasive pneumococcal infection. EndA's role in DNA uptake during transformation contributes to gene transfer and genetic diversification. Moreover, EndA's nuclease activity degrades the DNA backbone of neutrophil extracellular traps (NETs), allowing pneumococcus to escape host immune responses. Given its potential impact on pneumococcal pathogenicity, EndA is an attractive target for novel antimicrobial therapy. Herein, we describe the development of a high-throughput screening assay for the discovery of nuclease inhibitors. Nuclease-mediated digestion of double-stranded DNA was assessed using fluorescence changes of the DNA dye ligand, PicoGreen. Under optimized conditions, the assay provided robust and reproducible activity data (Z'= 0.87) and was used to screen 4727 small molecules against an imidazole-rescued variant of EndA. In total, six small molecules were confirmed as novel EndA inhibitors, some of which may have utility as research tools for understanding pneumococcal pathogenesis and for drug discovery.
C1 [Peterson, Eliza J. R.; Singleton, Scott F.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
[Kireev, Dmitri; Janzen, William P.; Singleton, Scott F.] Univ N Carolina, UNC Eshelman Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
[Moon, Andrea F.; Pedersen, Lars C.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Midon, Marika; Pingoud, Alfred] Univ Giessen, D-35390 Giessen, Germany.
RP Singleton, SF (reprint author), Univ N Carolina, UNC Eshelman Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
EM scott_singleton@unc.edu
FU National Institutes of Health; National Institute of General Medical
Sciences [GM058114]; Division of Intramural Research of the National
Institute of Environmental Health Sciences [1 ZIA ES102645-03]; Deutsche
Forschungsgemeinschaft; National Center for Research Resources; National
Center for Advancing Translational Sciences [UL1TR000083]
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This work was
supported by the National Institutes of Health, including a grant to S.
F. S. from the National Institute of General Medical Sciences (grant
number GM058114), a grant to L. C. P. from the Division of Intramural
Research of the National Institute of Environmental Health Sciences
(grant number 1 ZIA ES102645-03), a grant (ECCPS) to M. M. from the
Deutsche Forschungsgemeinschaft, and support from the National Center
for Research Resources and the National Center for Advancing
Translational Sciences (grant number UL1TR000083).
NR 34
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U1 0
U2 24
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD MAR
PY 2013
VL 18
IS 3
BP 247
EP 257
DI 10.1177/1087057112461153
PG 11
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA 087OM
UT WOS:000314771500002
PM 23015019
ER
PT J
AU Naujokas, MF
Anderson, B
Ahsan, H
Aposhian, HV
Graziano, JH
Thompson, C
Suk, WA
AF Naujokas, Marisa F.
Anderson, Beth
Ahsan, Habibul
Aposhian, H. Vasken
Graziano, Joseph H.
Thompson, Claudia
Suk, William A.
TI The Broad Scope of Health Effects from Chronic Arsenic Exposure: Update
on a Worldwide Public Health Problem
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Review
DE arsenic; arsenic health effects; cancer; chronic arsenic exposure;
development; drinking water; skin lesions
ID LONGITUDINAL-STUDY HEALS; INDUCED SKIN-LESIONS; DRINKING-WATER;
CANCER-MORTALITY; LUNG-CANCER; OXIDATIVE STRESS; DNA METHYLATION;
BLADDER-CANCER; NORTHERN CHILE; WEST-BENGAL
AB BACKGROUND: Concerns for arsenic exposure are not limited to toxic waste sites and massive poisoning events. Chronic exposure continues to be a major public health problem worldwide, affecting hundreds of millions of persons.
OBJECTIVES: We reviewed recent information on worldwide concerns for arsenic exposures and public health to heighten awareness of the current scope of arsenic exposure and health outcomes and the importance of reducing exposure, particularly during pregnancy and early life.
METHODS: We synthesized the large body of current research pertaining to arsenic exposure and health outcomes with an emphasis on recent publications.
DISCUSSION: Locations of high arsenic exposure via drinking water span from Bangladesh, Chile, and Taiwan to the United States. The U. S. Environmental Protection Agency maximum contaminant level (MCL) in drinking water is 10 mu g/L; however, concentrations of > 3,000 mu g/L have been found in wells in the United States. In addition, exposure through diet is of growing concern. Knowledge of the scope of arsenic-associated health effects has broadened; arsenic leaves essentially no bodily system untouched. Arsenic is a known carcinogen associated with skin, lung, bladder, kidney, and liver cancer. Dermatological, developmental, neurological, respiratory, cardiovascular, immunological, and endocrine effects are also evident. Most remarkably, early-life exposure may be related to increased risks for several types of cancer and other diseases during adulthood.
CONCLUSIONS: These data call for heightened awareness of arsenic-related pathologies in broader contexts than previously perceived. Testing foods and drinking water for arsenic, including individual private wells, should be a top priority to reduce exposure, particularly for pregnant women and children, given the potential for life-long effects of developmental exposure.
C1 [Naujokas, Marisa F.] MDB Inc, Durham, NC 27713 USA.
[Anderson, Beth; Suk, William A.] NIEHS, Superfund Res Program, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Ahsan, Habibul] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Ahsan, Habibul] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Ahsan, Habibul] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Aposhian, H. Vasken] Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA.
[Graziano, Joseph H.] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA.
[Thompson, Claudia] NIEHS, Susceptibil & Populat Hlth Branch, Superfund Res Program, NIH,DHHS, Res Triangle Pk, NC 27709 USA.
RP Naujokas, MF (reprint author), MDB Inc, Meridian Corp Ctr 2525, Suite 50, Durham, NC 27713 USA.
EM naujokasmf@niehs.nih.gov
RI Calderon, Jaqueline/B-5841-2014
OI Calderon, Jaqueline/0000-0002-7865-3357
FU National Institute of Environmental Health Sciences (NIEHS)
[GS-OOF-0001S]; National Institute of Environmental Health Sciences
(NIEHS) (Health and Human Services) [CR700013]; National Institutes of
Health; NIEHS SRP [P42ES10349, RO1CA107431, RO1CA102484]
FX M.F.N. is supported through a contract with the National Institute of
Environmental Health Sciences (NIEHS) Superfund Research Program (SRP)
(contract GS-OOF-0001S, Health and Human Services order CR700013). H. A.
is supported by National Institutes of Health and NIEHS SRP grants
P42ES10349, RO1CA107431, and RO1CA102484. J.G. is supported by NIEHS SRP
grant P42ES10349.
NR 140
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U2 165
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAR
PY 2013
VL 121
IS 3
BP 295
EP 302
DI 10.1289/ehp.1205875
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 208TU
UT WOS:000323703500019
PM 23458756
ER
PT J
AU Snijder, CA
Heederik, D
Pierik, FH
Hofman, A
Jaddoe, VW
Koch, HM
Longnecker, MP
Burdorf, A
AF Snijder, Claudia A.
Heederik, Dick
Pierik, Frank H.
Hofman, Albert
Jaddoe, Vincent W.
Koch, Holger M.
Longnecker, Matthew P.
Burdorf, Alex
TI Fetal Growth and Prenatal Exposure to Bisphenol A: The Generation R
Study
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE birth weight; bisphenol A; fetal growth; head circumference; pregnancy;
urine
ID IN-UTERO EXPOSURE; BIRTH OUTCOMES; ENDOCRINE DISRUPTERS; PREGNANT-WOMEN;
ULTRASOUND; CHEMICALS; ESTROGEN; WEIGHT; HEALTH; PHYTOESTROGENS
AB BACKGROUND: Prenatal exposure to bisphenol A (BPA) has been associated with adverse birth outcomes, but findings of previous studies have been inconsistent.
OBJECTIVE: We investigated the relation of prenatal BPA exposure with intrauterine growth and evaluated the effect of the number of measurements per subject on observed associations.
METHODS: This study was embedded in a Dutch population-based prospective cohort study, with urine samples collected during early, mid-, and late pregnancy. The study comprised 219 women, of whom 99 had one measurement, 40 had two measurements, and 80 had three measurements of urinary BPA. Fetal growth characteristics were repeatedly measured by ultrasound during pregnancy and combined with measurements at birth. Linear regression models for repeated measurements of both BPA and fetal growth were used to estimate associations between urinary concentrations of creatinine-based BPA (BPA(CB)) and intrauterine growth.
RESULTS: The relationship between BPA(CB) and fetal growth was sensitive to the number of BPA measurements per woman. Among 80 women with three BPA measurements, women with BPA(CB) > 4.22 mu g/g crea (creatinine) had lower growth rates for fetal weight and head circumference than did women with BPA(CB) < 1.54 mu g/g crea, with estimated differences in mean values at birth of -683 g (20.3% of mean) and -3.9 cm (11.5% of mean), respectively. When fewer measurements were available per woman, the exposure-response relationship became progressively attenuated and statistically nonsignificant.
CONCLUSION: Our findings suggest that maternal urinary BPA may impair fetal growth. Because previous studies have shown contradictory findings, further evidence is needed to corroborate these findings in the general population.
C1 [Snijder, Claudia A.; Hofman, Albert; Jaddoe, Vincent W.] Erasmus MC, Generat Study Grp R, NL-3000 CA Rotterdam, Netherlands.
[Snijder, Claudia A.; Burdorf, Alex] Erasmus MC, Dept Publ Hlth, NL-3000 CA Rotterdam, Netherlands.
[Heederik, Dick] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Pierik, Frank H.] TNO Netherlands Org Appl Sci Res, Dept Urban Environm & Safety, Utrecht, Netherlands.
[Hofman, Albert; Jaddoe, Vincent W.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
[Jaddoe, Vincent W.] Erasmus MC, Dept Pediat, NL-3000 CA Rotterdam, Netherlands.
[Koch, Holger M.] Inst Ruhr Univ, German Social Accid Insurance, Inst Prevent & Occupat Med, Bochum, Germany.
[Longnecker, Matthew P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Burdorf, A (reprint author), Erasmus MC, Dept Publ Hlth, POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM a.burdorf@erasmusmc.nl
RI Koch, Holger/B-3277-2011;
OI Koch, Holger/0000-0002-8328-2837; Longnecker,
Matthew/0000-0001-6073-5322
FU European project CONTAMED; European Union [212502]; U.S. National
Institutes of Health, National Institute of Environmental Health
Sciences
FX The present study was conducted in commission of the European project
CONTAMED with funding from the European Union's Seventh Framework
Programme (FP7) for Research and Technology Development (EU grant
agreement 212502). This research was supported in part by the intramural
research program of the U.S. National Institutes of Health, National
Institute of Environmental Health Sciences.
NR 42
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U1 2
U2 31
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAR
PY 2013
VL 121
IS 3
BP 393
EP 398
DI 10.1289/ehp.1205296
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 208TU
UT WOS:000323703500033
PM 23459363
ER
PT J
AU Navas-Acien, A
Maull, EA
Thayer, KA
AF Navas-Acien, Ana
Maull, Elizabeth A.
Thayer, Kristina A.
TI Arsenic and Diabetes: Navas-Acien et al. Respond
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Letter
ID PREVALENCE; EXPOSURE
C1 [Navas-Acien, Ana] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA.
[Maull, Elizabeth A.; Thayer, Kristina A.] NIH, Natl Inst Environm Hlth Sci, Dept Hlth & Human Serv, Div Natl Toxicol Program, Res Triangle Pk, NC USA.
RP Navas-Acien, A (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA.
EM maull@niehs.nih.gov
NR 8
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U1 1
U2 3
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAR
PY 2013
VL 121
IS 3
BP A71
EP A72
DI 10.1289/ehp.1206100R
PG 3
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 208TU
UT WOS:000323703500005
PM 23455044
ER
PT J
AU LaLonde, JM
Le-Khac, M
Jones, DM
Courter, JR
Park, J
Schon, A
Princiotto, AM
Wu, XL
Mascola, JR
Freire, E
Sodroski, J
Madani, N
Hendrickson, WA
Smith, AB
AF LaLonde, Judith M.
Le-Khac, Matthew
Jones, David M.
Courter, Joel R.
Park, Jongwoo
Schoen, Arne
Princiotto, Amy M.
Wu, Xueling
Mascola, John R.
Freire, Ernesto
Sodroski, Joseph
Madani, Navid
Hendrickson, Wayne A.
Smith, Amos B., III
TI Structure-Based Design and Synthesis of an HIV-1 Entry Inhibitor
Exploiting X-ray and Thermodynamic Characterization
SO ACS MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE HIV; gp120; CD4; entry inhibitor; structure-based drug design;
thermodynamics; X-ray crystallography; viral inhibition; protein-protein
interactions
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEINS; GP120; CD4;
BINDING; RECEPTOR; ANTIBODY; COMPLEX; MIMICS
AB The design, synthesis, thermodynamic and crystallographic characterization of a potent, broad spectrum, second-generation HIV-1 entry inhibitor that engages conserved carbonyl hydrogen bonds within gp120 has been achieved. The optimized antagonist exhibits a submicromolar binding affinity (110 nM) and inhibits viral entry of clade B and C viruses (IC50 geometric mean titer of 1.7 and 14.0 mu M, respectively), without promoting CD4-independent viral entry. The thermodynamic signatures indicate a binding preference for the (R,R)- over the (S,S)-enantiomer. The crystal structure of the small-molecule/gp120 complex reveals the displacement of crystallographic water and the formation of a hydrogen bond with a backbone carbonyl of the bridging sheet. Thus, structure-based design and synthesis targeting the highly conserved and structurally characterized CD4-gp120 interface is an effective tactic to enhance the neutralization potency of small-molecule HIV-1 entry inhibitors.
C1 [LaLonde, Judith M.] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA.
[Le-Khac, Matthew] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA.
[Le-Khac, Matthew; Hendrickson, Wayne A.] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
[Jones, David M.; Courter, Joel R.; Park, Jongwoo; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.
[Schoen, Arne; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
[Princiotto, Amy M.; Sodroski, Joseph; Madani, Navid] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Wu, Xueling; Mascola, John R.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Sodroski, Joseph] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
[Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Sodroski, Joseph] Ragon Inst MGH MIT & Harvard, Boston, MA 02115 USA.
[Hendrickson, Wayne A.] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
RP LaLonde, JM (reprint author), Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA.
EM jlalonde@brynmawr.edu; wayne@xtl.cumc.columbia.edu;
smithab@sas.upenn.edu
FU NIH [GM 56550, AI090682-01]; NIH Intramural IATAP; NIAID programs; Ragon
Institute of MGH; Ragon Institute of MIT; Ragon Institute of Harvard
FX Funding was provided by NIH GM 56550 to J.M.L., E.F., WA.H., A.B.S., and
J.S. and by NIH Intramural IATAP and NIAID programs to J.R.M. and J.S.
Funding to N.M. was provided by NIH AI090682-01. N.M. and J.S. were also
supported by Ragon Institute of MGH, MIT, and Harvard.
NR 27
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U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-5875
J9 ACS MED CHEM LETT
JI ACS Med. Chem. Lett.
PD MAR
PY 2013
VL 4
IS 3
BP 338
EP 343
DI 10.1021/ml300407y
PG 6
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 207JD
UT WOS:000323593800006
PM 23667716
ER
PT J
AU Miller, FG
AF Miller, Franklin G.
TI TWO PHILOSOPHICAL DEATHS Hume and Hitchens
SO PERSPECTIVES IN BIOLOGY AND MEDICINE
LA English
DT Article
AB This essay describes the deaths of David Hume (1711-1776) and Christopher Hitchens (1949-2012). Both distinguished thinkers and writers, who shared much in their world views, died around the same age after a similarly prolonged course of terminal illness. However, the great difference in the power of medicine to intervene with the goal of cure or preserving life made their lives while facing death dramatically different. The narratives of these two deaths help shed light on some of the key features that make particular deaths and the processes of dying good or bad, as well as highlight the difficulty in achieving a good death in the world of contemporary medicine.
C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
FU Intramural Research Program of the Clinical Center, NIH
FX This research was supported by the Intramural Research Program of the
Clinical Center, NIH.
NR 12
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U1 1
U2 3
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 0031-5982
J9 PERSPECT BIOL MED
JI Perspect. Biol. Med.
PD SPR
PY 2013
VL 56
IS 2
BP 251
EP 258
PG 8
WC History & Philosophy Of Science; Medicine, Research & Experimental
SC History & Philosophy of Science; Research & Experimental Medicine
GA 203ND
UT WOS:000323299000007
PM 23974505
ER
PT J
AU Crane, NJ
Huffman, SW
Alemozaffar, M
Gage, FA
Levin, IW
Elster, EA
AF Crane, Nicole J.
Huffman, Scott W.
Alemozaffar, Mehrdad
Gage, Frederick A.
Levin, Ira W.
Elster, Eric A.
TI Evidence of a heterogeneous tissue oxygenation: renal
ischemia/reperfusion injury in a large animal model
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE visible reflectance spectroscopy; oxygenation; kidney; swine
ID VISIBLE-LIGHT SPECTROSCOPY; LEAST-SQUARES METHODS; PARTIAL NEPHRECTOMY;
INFRARED-SPECTROSCOPY; ISCHEMIA; KIDNEY; ARTERY; FLOW
AB Renal ischemia that occurs intraoperatively during procedures requiring clamping of the renal artery (such as renal procurement for transplantation and partial nephrectomy for renal cancer) is known to have a significant impact on the viability of that kidney. To better understand the dynamics of intraoperative renal ischemia and recovery of renal oxygenation during reperfusion, a visible reflectance imaging system (VRIS) was developed to measure renal oxygenation during renal artery clamping in both cooled and warm porcine kidneys. For all kidneys, normothermic and hypothermic, visible reflectance imaging demonstrated a spatially distinct decrease in the relative oxy-hemoglobin concentration (%HbO(2)) of the superior pole of the kidney compared to the middle or inferior pole. Mean relative oxy-hemoglobin concentrations decrease more significantly during ischemia for normothermic kidneys compared to hypothermic kidneys. VRIS may be broadly applicable to provide an indicator of organ ischemia during open and laparoscopic procedures. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
C1 [Crane, Nicole J.; Gage, Frederick A.; Elster, Eric A.] Naval Med Res Ctr, Dept Regenerat Med, Silver Spring, MD 20910 USA.
[Huffman, Scott W.] Western Carolina Univ, Dept Chem & Phys, Cullowhee, NC 28723 USA.
[Alemozaffar, Mehrdad] Univ So Calif, Inst Urol, Norris Canc Ctr, Los Angeles, CA 90089 USA.
[Gage, Frederick A.; Elster, Eric A.] Walter Reed Natl Mil Med Ctr, Dept Surg, Bethesda, MD 20814 USA.
[Levin, Ira W.] NIDDK, Chem Phys Lab, Natl Inst Hlth, Bethesda, MD USA.
[Crane, Nicole J.; Elster, Eric A.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA.
RP Elster, EA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Surg, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM eric.elster@usuhs.edu
FU Department of Defense [602227D.0483.01.A0518]; National Institute of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health
FX The authors thank Drs. Nadeem Dhanani, Marie McHenry, Ben McHone, and
Peter Pinto for their surgical assistance during the experiments. This
effort was supported (in part) by the Department of Defense (work unit
no. 602227D.0483.01.A0518, Medical Free Electron Laser Program). We also
acknowledge support from the intramural program of the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health. The experiments reported herein were conducted in
compliance with the Animal Welfare Act and in accordance with the
principles set forth in the "Guide for the Care and Use of Laboratory
Animals," Institute of Laboratory Animals Resources, National Research
Council, National Academy Press, 1996. The views expressed in this
manuscript are those of the authors and do not reflect the official
policy of the Department of the Army, Department of the Navy, the
Department of Defense, or the U.S. government. This work was prepared as
part of official government duties. Title 17 U.S.C. 105 provides that
"Copyright protection under this title is not available for any work of
the United States government." Title 17 U.S.C. 101 defines a U. S.
government work as a work prepared by a military service member or
employee of the U. S. government as part of that person's official
duties. We certify that all individuals who qualify as authors have been
listed; each has participated in the conception and design of this work,
the analysis of data (when applicable), the writing of the document, and
the approval of the submission of this version; that the document
represents valid work; that if we used information derived from another
source, we obtained all necessary approvals to use it and made
appropriate acknowledgements in the document; and that each author takes
public responsibility for it.
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PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD MAR
PY 2013
VL 18
IS 3
AR 035001
DI 10.1117/1JBO.18.3.035001
PG 7
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 190JV
UT WOS:000322336700016
PM 23456040
ER
PT J
AU Liu, JK
Hickson, DA
Musani, SK
Talegawkar, SA
Carithers, TC
Tucker, KL
Fox, CS
Taylor, HA
AF Liu, Jiankang
Hickson, DeMarc A.
Musani, Solomon K.
Talegawkar, Sameera A.
Carithers, Teresa C.
Tucker, Katherine L.
Fox, Caroline S.
Taylor, Herman A.
TI Dietary Patterns, Abdominal Visceral Adipose Tissue, and Cardiometabolic
Risk Factors in African Americans: The Jackson Heart Study
SO OBESITY
LA English
DT Article
ID METABOLIC SYNDROME; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE;
PHYSICAL-ACTIVITY; FAT; ADULTS; WOMEN; LIVER
AB Objective: To examine the relative association of abdominal visceral adipose tissue (VAT) with cardiometabolic risk factors between African and European Americans.
Design and Methods: We conducted a cross-sectional study of 2035 African Americans from Jackson Heart Study (JHS) and 3170 European Americans from Framingham Heart Study (FHS) who underwent computed tomography assessment of VAT and subcutaneous adipose tissue (SAT). The FHS participants were weighted to match the age distribution of the JHS participants and the metabolic risk factors were examined by study groups in relation to VAT.
Results: JHS participants had higher rates of obesity, hypertension, diabetes and metabolic syndrome than FHS participants (all p = 0.001). The associations were weaker in JHS women for VAT with blood pressure, triglycerides, HDL-C, and total cholesterol (p(interaction) = 0.03 to 0.001) than FHS women. In contrast, JHS men had stronger associations for VAT with high triglycerides, low HDL, and metabolic syndrome (all p(interaction) = 0.001) compared to FHS men. Similar associations and gender patterns existed for SAT with most metabolic risk factors.
Conclusions: The relative association between VAT and cardiometabolic risk factors is weaker in JHS women compared to FHS women, whereas stronger association with triglycerides and HDL were observed in JHS men.
C1 [Liu, Jiankang; Hickson, DeMarc A.; Musani, Solomon K.; Taylor, Herman A.] Jackson State Univ, Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS USA.
[Talegawkar, Sameera A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Carithers, Teresa C.] Univ Mississippi, Dept Family & Consumer Sci, Oxford, MS USA.
[Tucker, Katherine L.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
RP Liu, JK (reprint author), Jackson State Univ, Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS USA.
EM jliu@umc.edu
OI Tucker, Katherine/0000-0001-7640-662X
FU National Heart, Lung, and Blood Institute [N01-HC-95170, N01-HC-95171,
N01-C-95172]; National Center on Minority Health and Health Disparities
FX The authors thank the staff, interns, and participants in Jackson Heart
Study for their long-term commitment and important contributions to the
study. The Jackson Heart Study is supported by the National Heart, Lung,
and Blood Institute and the National Center on Minority Health and
Health Disparities. Funding for H.A.T. was provided under contracts
N01-HC-95170, N01-HC-95171, and N01-C-95172 from the National Heart,
Lung, and Blood Institute and the National Center on Minority Health and
Health Disparities.
NR 28
TC 17
Z9 17
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD MAR
PY 2013
VL 21
IS 3
BP 644
EP 651
DI 10.1038/oby.2012.145
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 187AK
UT WOS:000322087600057
PM 23592674
ER
PT J
AU Sanz-Clemente, A
Gray, JA
Ogilvie, KA
Nicoll, RA
Roche, KW
AF Sanz-Clemente, Antonio
Gray, John A.
Ogilvie, Kyle A.
Nicoll, Roger A.
Roche, Katherine W.
TI Activated CaMKII Couples GluN2B and Casein Kinase 2 to Control Synaptic
NMDA Receptors
SO CELL REPORTS
LA English
DT Article
ID D-ASPARTATE RECEPTOR; LONG-TERM POTENTIATION; SUBUNIT COMPOSITION;
DENDRITIC SPINES; NR2B SUBUNIT; VISUAL-CORTEX; PHOSPHORYLATION;
TRAFFICKING; PLASTICITY; BINDING
AB Synaptic activity triggers a profound reorganization of the molecular composition of excitatory synapses. For example, NMDA receptors are removed from synapses in an activity- and calcium-dependent manner, via casein kinase 2 (CK2) phosphorylation of the PDZ ligand of the GluN2B subunit (S1480). However, how synaptic activity drives this process remains unclear because CK2 is a constitutively active kinase, which is not directly regulated by calcium. We show here that activated CaMKII couples GluN2B and CK2 to form a trimolecular complex and increases CK2-mediated phosphorylation of GluN2B S1480. In addition, a GluN2B mutant, which contains an insert to mimic the GluN2A sequence and cannot bind to CaMKII, displays reduced S1480 phosphorylation and increased surface expression. We find that although disrupting GluN2B/CaMKII binding reduces synapse number, it increases synaptic-GluN2B content. Therefore, the GluN2B/CaMKII association controls synapse density and PSD composition in an activity-dependent manner, including recruitment of CK2 for the removal of GluN2B from synapses.
C1 [Sanz-Clemente, Antonio; Ogilvie, Kyle A.; Roche, Katherine W.] NINDS, Natl Inst Hlth, Receptor Biol Sect, Bethesda, MD 20892 USA.
[Gray, John A.; Nicoll, Roger A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
[Nicoll, Roger A.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
RP Roche, KW (reprint author), NINDS, Natl Inst Hlth, Receptor Biol Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM rochek@ninds.nih.gov
OI Roche, Katherine/0000-0001-7282-6539
FU NINDS Intramural Research Program; NIMH; NARSAD Young Investigator
Award; NARSAD Hammerschlag Family Investigator
FX We thank John D. Badger II for technical assistance. We also thank the
NINDS sequencing facility and light imaging facility for expertise and
advice. This research was supported by the NINDS Intramural Research
Program (A.S.-C., K.A.O., and K.W.R.) and grants from the NIMH (J.A.G.
and R.A.N.). J.A.G. is funded by a NARSAD Young Investigator Award and
is the NARSAD Hammerschlag Family Investigator.
NR 40
TC 20
Z9 21
U1 1
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD MAR
PY 2013
VL 3
IS 3
BP 607
EP 614
DI 10.1016/j.celrep.2013.02.011
PG 8
WC Cell Biology
SC Cell Biology
GA 184MZ
UT WOS:000321896000003
PM 23478024
ER
PT J
AU Bravo, PE
Zimmerman, SL
Luo, HC
Pozios, I
Rajaram, M
Pinheiro, A
Steenbergen, C
Kamel, IR
Wahl, RL
Bluemke, DA
Bengel, FM
Abraham, MR
Abraham, TP
AF Bravo, Paco E.
Zimmerman, Stefan L.
Luo, Hong-Chang
Pozios, Iraklis
Rajaram, Mahadevan
Pinheiro, Aurelio
Steenbergen, Charles
Kamel, Ihab R.
Wahl, Richard L.
Bluemke, David A.
Bengel, Frank M.
Abraham, M. Roselle
Abraham, Theodore P.
TI Relationship of Delayed Enhancement by Magnetic Resonance to Myocardial
Perfusion by Positron Emission Tomography in Hypertrophic Cardiomyopathy
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Article
DE cardiac MRI; fibrosis; HCM; ischemia; PET
ID CORONARY MICROVASCULAR DYSFUNCTION; LATE GADOLINIUM ENHANCEMENT; FLOW
RESERVE; CONTRAST ENHANCEMENT; RISK-ASSESSMENT; QUANTIFICATION;
ARRHYTHMIAS; ISCHEMIA; FIBROSIS; ARTERIES
AB Background
Presence of delayed enhancement (DE) on cardiac magnetic resonance (CMR) is associated with worse clinical outcomes in hypertrophic cardiomyopathy. We investigated the relationship between DE on CMR and myocardial ischemia in hypertrophic cardiomyopathy.
Methods and Results
Hypertrophic cardiomyopathy patients (n=47) underwent CMR for assessment of DE and vasodilator stress ammonia positron emission tomography to quantify myocardial blood flow and coronary flow reserve. The summed difference score for regional myocardial perfusion was also assessed. Patients in the DE group (n=35) had greater left ventricular wall thickness (2.09 +/- 0.44 versus 1.78 +/- 0.34 cm; P=0.03). Stress myocardial blood flow (2.25 +/- 0.46 versus 1.78 +/- 0.43 mL/min per gram; P=0.01) and coronary flow reserve (2.78 +/- 0.32 versus 2.01 +/- 0.52; P<0.001) were significantly lower in DE-positive patients. Summed difference score (median, 5 versus 0; P<0.0001) was significantly higher in patients with DE. A coronary flow reserve <2.00 was seen in 18 patients (51%) with DE but in none of the DE-negative patients (P<0.0001). CMR and positron emission tomography showed visually concordant DE and regional myocardial perfusion abnormalities in 31 patients and absence of DE and perfusion defects in 9 patients. Four DE-positive patients demonstrated normal regional myocardial perfusion, and 3 DE-negative patients had (apical) regional myocardial perfusion abnormalities.
Conclusions
We found a close relationship between DE by CMR and microvascular function in most of the patients studied. However, a small proportion of patients had DE in the absence of perfusion abnormalities, suggesting that microvascular dysfunction and ischemia are not the sole causes of DE in hypertrophic cardiomyopathy patients.
C1 [Bravo, Paco E.; Zimmerman, Stefan L.; Rajaram, Mahadevan; Kamel, Ihab R.; Wahl, Richard L.; Bluemke, David A.] Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21205 USA.
[Luo, Hong-Chang; Pozios, Iraklis; Pinheiro, Aurelio; Abraham, M. Roselle; Abraham, Theodore P.] Johns Hopkins Med Inst, Div Cardiol, Baltimore, MD 21205 USA.
[Steenbergen, Charles] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
[Bluemke, David A.] NIH, Bethesda, MD 20892 USA.
[Luo, Hong-Chang] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Med Ultrasound, Wuhan 430074, Peoples R China.
[Bengel, Frank M.] Hannover Med Sch, Dept Nucl Med, Hannover, Germany.
RP Abraham, TP (reprint author), Johns Hopkins Univ, Sch Med, CARNEGIE 568B,600 N Wolfe St,Blalock 910F, Baltimore, MD 21287 USA.
EM tabraha3@jhmi.edu
OI Bluemke, David/0000-0002-8323-8086
FU National Institutes of Health [HL098046]
FX This work was supported in part by a grant from the National Institutes
of Health (HL098046).
NR 38
TC 14
Z9 14
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-9651
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD MAR
PY 2013
VL 6
IS 2
BP 210
EP 217
DI 10.1161/CIRCIMAGING.112.000110
PG 8
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 167XM
UT WOS:000320668800012
PM 23418294
ER
PT J
AU Lai, C
Wilson, W
AF Lai, Catherine
Wilson, Wyndham
TI T-cell lymphoma Preface
SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
LA English
DT Editorial Material
C1 [Lai, Catherine; Wilson, Wyndham] NCI, NIH, Bethesda, MD 20892 USA.
RP Lai, C (reprint author), NCI, NIH, 10 Ctr Dr,Bldg 10,Room 12N226, Bethesda, MD 20892 USA.
EM Catherine.lai@nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1521-6926
J9 BEST PRACT RES CL HA
JI Best Pract. Res. Clin. Haematol.
PD MAR
PY 2013
VL 26
IS 1
BP 1
EP 1
DI 10.1016/j.beha.2013.05.001
PG 1
WC Hematology
SC Hematology
GA 174RR
UT WOS:000321173600001
PM 23768635
ER
PT J
AU Lai, C
Dunleavy, K
AF Lai, Catherine
Dunleavy, Kieron
TI NK/T-cell lymphomas in children
SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
LA English
DT Article
DE T-lymphoblastic lymphoma; T-LBL; anaplastic large cell lymphoma; ALCL;
ALK; PTCL-NOS; angioimmunoblastic T-cell lymphoma; AITL; NOTCH1; mTOR;
CD30
ID PERIPHERAL T-CELL; ACUTE-LYMPHOBLASTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA;
BONE-MARROW-TRANSPLANTATION; FRANKFURT-MUNSTER GROUP; ONCOLOGY-GROUP;
PEDIATRIC-ONCOLOGY; BFM-GROUP; CLINICAL-FEATURES; DOSE METHOTREXATE
AB In children, T and NK-cell lymphomas are uncommon in Western Countries. While there has been significant experience treating T-cell lymphoblastic lymphoma (T-LBL) and anaplastic large cell lymphoma (ALCL), other subtypes are very rarely encountered and there are no standard approaches to their management. There are many challenges in defining optimal therapy for many of these diseases but recent progress in elucidating their biology has led to new molecular insights and identified interesting targets for novel drug discovery. In this review, we discuss these disorders in children, how they are approached therapeutically and what lies on the horizon with respect to novel treatment approaches. Published by Elsevier Ltd.
C1 [Lai, Catherine; Dunleavy, Kieron] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Dunleavy, K (reprint author), NCI, Bldg 10,Rm 12N226,10 Ctr Dr, Bethesda, MD 20892 USA.
EM dunleavk@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 72
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1521-6926
J9 BEST PRACT RES CL HA
JI Best Pract. Res. Clin. Haematol.
PD MAR
PY 2013
VL 26
IS 1
BP 33
EP 41
DI 10.1016/j.beha.2013.04.004
PG 9
WC Hematology
SC Hematology
GA 174RR
UT WOS:000321173600005
PM 23768639
ER
PT J
AU Bajor-Dattilo, EB
Pittaluga, S
Jaffe, ES
AF Bajor-Dattilo, Ewa B.
Pittaluga, Stefania
Jaffe, Elaine S.
TI Pathobiology of T-cell and NK-cell lymphomas
SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
LA English
DT Article
DE pathobiology; pathogenesis; anaplastic large cell lymphoma; peripheral
T-cell lymphoma; extranodal NK/T-cell lymphoma; enteropathy associated
T-cell lymphoma; hepatosplenic T-cell lymphoma; subcutaneous
panniculitis-like T-cell lymphoma; primary cutaneous gamma delta T-cell
lymphoma; cellular origin; nodal; extranodal; innate immune system;
adaptive immune system; T-follicular helper cells; alpha beta T-cell
receptor; gamma delta T-cell receptor
ID EPSTEIN-BARR-VIRUS; CLASSICAL HODGKIN LYMPHOMA; FOLLICULAR-GROWTH
PATTERN; GAMMA-DELTA; B-CELL; LYMPHOPROLIFERATIVE DISORDERS;
ANGIOIMMUNOBLASTIC LYMPHADENOPATHY; CLINICOPATHOLOGICAL ENTITY;
GENE-EXPRESSION; CELIAC-DISEASE
AB T-cell and NK-cell lymphomas are uncommon lymphomas with an aggressive clinical course. The causes and precise cellular origins of most T-cell lymphomas are still not well defined. The WHO classification utilizes morphologic and immunophenotypic features in conjunction with clinical aspects and in some instances genetics to delineate a prognostically and therapeutically meaningful categorization. The anatomic localization of neoplastic T-cells and NK-cells parallels in part their proposed normal cellular counterparts and functions. T-cells of the adaptive immune system are mainly based in lymph nodes and peripheral blood, whereas lymphomas derived from T-cells and NK-cells of the innate immune system are mainly extranodal. This approach allows for better understanding of some of the manifestations of the T-cell and NK-cell lymphomas, including their cellular distribution, some aspects of morphology and even associated clinical findings. Published by Elsevier Ltd.
C1 [Bajor-Dattilo, Ewa B.; Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
RP Jaffe, ES (reprint author), NCI, Pathol Lab, Bldg 10,Room 2B42, Bethesda, MD 20892 USA.
EM ewa.bajor-dattilo@nih.gov; stefpitt@mail.nih.gov; ejaffe@mail.nih.gov
OI Jaffe, Elaine/0000-0003-4632-0301
FU Intramural NIH HHS [ZIA BC011070-05]
NR 94
TC 8
Z9 8
U1 0
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1521-6926
J9 BEST PRACT RES CL HA
JI Best Pract. Res. Clin. Haematol.
PD MAR
PY 2013
VL 26
IS 1
BP 75
EP 87
DI 10.1016/j.beha.2013.04.007
PG 13
WC Hematology
SC Hematology
GA 174RR
UT WOS:000321173600008
PM 23768642
ER
PT J
AU Moraitis, AG
Hewison, M
Collins, M
Anaya, C
Holick, MF
AF Moraitis, Andreas G.
Hewison, Martin
Collins, Michael
Anaya, Candido
Holick, Michael F.
TI HYPERCALCEMIA ASSOCIATED WITH MINERAL OIL-INDUCED SCLEROSING
PARAFFINOMAS
SO ENDOCRINE PRACTICE
LA English
DT Article
ID ANGIOTENSIN-CONVERTING ENZYME; SUBCUTANEOUS FAT NECROSIS; D-MEDIATED
HYPERCALCEMIA; VITAMIN-D; 25-HYDROXYVITAMIN D-3-1-ALPHA-HYDROXYLASE;
SARCOIDOSIS; NEWBORN; 1-ALPHA-HYDROXYLASE; EXPRESSION; GRANULOMAS
AB Objective: Granuloma-forming diseases such as sarcoidosis are associated with extrarenal synthesis of 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. We describe a case of extensive skin lesions associated with mineral oil injections in which we provide evidence for cutaneous granuloma synthesis of 1,25(OH)(2)D in the pathogenesis of the patient's hypercalcemia.
Methods: Analysis of expression of the 25(OH) D-1a-hydroxylase (1-a OHase [CYP27b1]) was carried out by immunohistochemical analysis of involved skin.
Results: In involved skin, expression of CYP27b1 was found in the dermis, where it is not normally expressed. Successful management of hypercalcemia was achieved with glucocorticoids.
Conclusions: Hypercalcemia associated with mineral oil induced skin lesions is likely driven by unregulated expression of CYP27b1 by inflammatory monocytes and macrophages infiltrating the dermis.
C1 [Moraitis, Andreas G.] Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Hewison, Martin] Univ Calif Los Angeles, David Geffen Sch Med, Orthopaed Hosp, Res Ctr, Los Angeles, CA 90095 USA.
[Hewison, Martin] Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, New York, NY USA.
[Collins, Michael] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, New York, NY USA.
[Anaya, Candido] New York Downtown Hosp Weill Cornell, New York, NY USA.
[Holick, Michael F.] Boston Univ, Sch Med, Dept Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA.
RP Moraitis, AG (reprint author), Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
EM moraitia@mail.nih.gov
OI Holick, Michael/0000-0001-6023-9062
FU New York Downtown Hospital; UCLA Orthopaedic Hospital Research Center
FX The authors have no multiplicity of interest to disclose. This work was
funded by the New York Downtown Hospital and the UCLA Orthopaedic
Hospital Research Center.
NR 25
TC 5
Z9 5
U1 0
U2 0
PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS
PI JACKSONVILLE
PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA
SN 1530-891X
J9 ENDOCR PRACT
JI Endocr. Pract.
PD MAR-APR
PY 2013
VL 19
IS 2
BP E50
EP E56
DI 10.4158/EP12092.CR
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 154JX
UT WOS:000319672400003
PM 23337133
ER
PT J
AU Romling, U
Galperin, MY
Gomelsky, M
AF Romling, Ute
Galperin, Michael Y.
Gomelsky, Mark
TI Cyclic di-GMP: the First 25 Years of a Universal Bacterial Second
Messenger
SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
LA English
DT Review
ID ENTERICA SEROVAR TYPHIMURIUM; 3',5'-CYCLIC DIGUANYLIC ACID; PILZ DOMAIN
PROTEINS; HD-GYP DOMAIN; REGULATES BIOFILM FORMATION; DIMERIC
GUANOSINE-MONOPHOSPHATE; PSEUDOMONAS-FLUORESCENS PF0-1;
SIGNAL-TRANSDUCTION SYSTEMS; GENERAL STRESS-RESPONSE; PRIME
TRANSCRIPTION INITIATION
AB Twenty-five years have passed since the discovery of cyclic dimeric (3'-> 5') GMP (cyclic di-GMP or c-di-GMP). From the relative obscurity of an allosteric activator of a bacterial cellulose synthase, c-di-GMP has emerged as one of the most common and important bacterial second messengers. Cyclic di-GMP has been shown to regulate biofilm formation, motility, virulence, the cell cycle, differentiation, and other processes. Most c-di-GMP-dependent signaling pathways control the ability of bacteria to interact with abiotic surfaces or with other bacterial and eukaryotic cells. Cyclic di-GMP plays key roles in lifestyle changes of many bacteria, including transition from the motile to the sessile state, which aids in the establishment of multicellular biofilm communities, and from the virulent state in acute infections to the less virulent but more resilient state characteristic of chronic infectious diseases. From a practical standpoint, modulating c-di-GMP signaling pathways in bacteria could represent a new way of controlling formation and dispersal of biofilms in medical and industrial settings. Cyclic di-GMP participates in interkingdom signaling. It is recognized by mammalian immune systems as a uniquely bacterial molecule and therefore is considered a promising vaccine adjuvant. The purpose of this review is not to overview the whole body of data in the burgeoning field of c-di-GMP-dependent signaling. Instead, we provide a historic perspective on the development of the field, emphasize common trends, and illustrate them with the best available examples. We also identify unresolved questions and highlight new directions in c-di-GMP research that will give us a deeper understanding of this truly universal bacterial second messenger.
C1 [Romling, Ute] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
[Galperin, Michael Y.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Gomelsky, Mark] Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA.
RP Romling, U (reprint author), Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
EM ute.romling@ki.se
OI Romling, Ute/0000-0003-3812-6621; Galperin, Michael/0000-0002-2265-5572
FU European Commission; Swedish Research Council of Natural Sciences;
Petrus and Augusta Hedlund Foundation; Carl Trygger Foundation; Swedish
Research Council of Medicine and Health; Karolinska Institutet;
Intramural Research Program of the National Institutes of Health at the
National Library of Medicine; NSF [MCB 1052575]; USDA [AFRI
2010-65201-20599]; University of Wyoming Agricultural Experiment Station
FX The work of our groups has been supported by the European Commission,
the Swedish Research Council of Natural Sciences, the Petrus and Augusta
Hedlund Foundation, the Carl Trygger Foundation, the Swedish Research
Council of Medicine and Health, and the Karolinska Institutet (U. R.);
by the Intramural Research Program of the National Institutes of Health
at the National Library of Medicine (M.Y.G.); and by grants from the NSF
(MCB 1052575), the USDA (AFRI 2010-65201-20599), and the University of
Wyoming Agricultural Experiment Station (M.G.).
NR 487
TC 389
Z9 397
U1 12
U2 169
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1092-2172
J9 MICROBIOL MOL BIOL R
JI Microbiol. Mol. Biol. Rev.
PD MAR
PY 2013
VL 77
IS 1
BP 1
EP 52
DI 10.1128/MMBR.00043-12
PG 52
WC Microbiology
SC Microbiology
GA 157NF
UT WOS:000319903400001
PM 23471616
ER
PT J
AU Kim, H
Stotts, NA
Froelicher, ES
Engler, MM
Porter, C
AF Kim, Hyunjung
Stotts, Nancy A.
Froelicher, Erika S.
Engler, Marguerite M.
Porter, Carol
TI ENTERAL NUTRITIONAL INTAKE IN ADULT KOREAN INTENSIVE CARE PATIENTS
SO AMERICAN JOURNAL OF CRITICAL CARE
LA English
DT Article
ID CRITICALLY-ILL PATIENTS; RECEIVING MECHANICAL VENTILATION; UNIT
PATIENTS; ICU PATIENTS; ENERGY-EXPENDITURE; CONTROLLED-TRIAL;
CALORIC-INTAKE; DELIVERY; SUPPORT; OUTCOMES
AB Background Nutritional support is important for maximizing clinical outcomes in critically ill patients, but enteral nutritional intake is often inadequate.
Objectives To assess the nutritional intake of energy and protein during the first 4 days after initiation of enteral feeding and to examine the relationship between intake and interruptions of enteral feeding in Korean patients in intensive care.
Methods A cohort of 34 critically ill adults who had a primary medical diagnosis and received bolus enteral feeding were studied prospectively. Energy and protein requirements were determined by using the Harris-Benedict equation and the American Dietetic Association equation. Energy and protein intake prescribed and received and the reasons for and lengths of feeding interruptions were recorded for 4 consecutive days immediately after enteral feeding began.
Results Although the differences between requirements and intakes of energy and protein decreased significantly, patients did not receive required energy and protein intake during the 4 days of the study. Energy intake prescribed was consistently less than required on each of the 4 days. Enteral nutrition was withheld for a mean of 6 hours per patient for the 4 days. Prolonged feeding interruptions due to gastrointestinal intolerance (r = -0.874; P < .001) and procedures (r = -0.839; P = .005) were negatively associated with the percentage of prescribed energy received.
Conclusion Enteral nutritional intake was insufficient in bolusfed Korean intensive care patients because of prolonged feeding interruptions and underprescription of enteral nutrition. Feeding interruptions due to gastrointestinal intolerance and procedures were the main contributors to inadequate energy intake. (American Journal of Critical Care. 2013; 22: 126-135)
C1 [Kim, Hyunjung] Hallym Univ, Div Nursing, Chunchon, Gangwon, South Korea.
[Stotts, Nancy A.; Froelicher, Erika S.] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA.
[Froelicher, Erika S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Engler, Marguerite M.] NINR, NIH, Bethesda, MD 20892 USA.
[Porter, Carol] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
RP Stotts, NA (reprint author), Univ Calif San Francisco, 2 Koret Way 631Y, San Francisco, CA 94143 USA.
EM nancy.stotts@nursing.ucsf.edu
FU Alpha Eta Chapter Research Award of Sigma Theta Tau International Honor
Society of Nursing; University of California San Francisco Graduate
Student Research Award; University of California San Francisco School of
Nursing Century Club Award
FX This study was supported by the Alpha Eta Chapter Research Award of
Sigma Theta Tau International Honor Society of Nursing, the University
of California San Francisco Graduate Student Research Award, and the
University of California San Francisco School of Nursing Century Club
Award.
NR 43
TC 5
Z9 5
U1 0
U2 5
PU AMER ASSOC CRITICAL CARE NURSES
PI ALISO VIEJO
PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA
SN 1062-3264
EI 1937-710X
J9 AM J CRIT CARE
JI Am. J. Crit. Care
PD MAR 1
PY 2013
VL 22
IS 2
BP 126
EP 135
DI 10.4037/ajcc2013629
PG 10
WC Critical Care Medicine; Nursing
SC General & Internal Medicine; Nursing
GA 153QL
UT WOS:000319617400007
PM 23455862
ER
PT J
AU Cook, NL
Bonds, DE
Kiefe, CI
Curtis, JP
Krumholz, HM
Kressin, NR
Peterson, ED
AF Cook, Nakela L.
Bonds, Denise E.
Kiefe, Catarina I.
Curtis, Jeptha P.
Krumholz, Harlan M.
Kressin, Nancy R.
Peterson, Eric D.
CA Natl Heart Lung Blood Inst Ctr Car
TI Centers for Cardiovascular Outcomes Research Defining a Collaborative
Vision
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE cross-collaboration; outcomes research; translation of knowledge
ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES;
PULMONARY-EMBOLISM; SECONDARY PREVENTION; INSURANCE STATUS; UNSTABLE
ANGINA; WHITE PATIENTS; DISEASE; HEART; RISK
AB Background-Recognizing the value of outcomes research to understand and bridge translational gaps, to establish evidence in clinical practice and delivery of medicine, and to generate new hypotheses on ongoing questions of treatment and care, the National Heart, Lung, and Blood Institute of the National Institutes of Health established the Centers for Cardiovascular Outcomes Research program in 2010.
Methods and Results-The National Heart, Lung, and Blood Institute funded 3 centers and a research coordinating unit. Each center has an independent project focus, including (1) characterizing care transition and predicting clinical events and quality of life for patients discharged after an acute coronary syndrome; (2) identifying center and regional factors associated with better patient outcomes across several cardiovascular conditions and procedures; and (3) examining the impact of healthcare reform in Massachusetts on overall and disparate care and outcomes for several cardiovascular conditions and venous thromboembolism. Cross-program collaborations seek to advance the field methodologically and to develop early-stage investigators committed to careers in outcomes research.
Conclusions-The Centers for Cardiovascular Outcomes Research program represents a significant investment in cardiovascular outcomes research by the National Heart, Lung, and Blood Institute. The vision of this program is to leverage scientific rigor and cross-program collaboration to advance the science of healthcare delivery and outcomes beyond what any individual unit could achieve alone.
C1 [Cook, Nakela L.] NHLBI, Bethesda, MD 20892 USA.
[Kiefe, Catarina I.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA.
[Curtis, Jeptha P.; Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Med, Sect Cardiovasc Med, New Haven, CT 06510 USA.
[Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA.
[Krumholz, Harlan M.] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Management, New Haven, CT USA.
[Curtis, Jeptha P.; Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA.
[Kressin, Nancy R.] Dept Vet Affairs, Boston, MA USA.
[Kressin, Nancy R.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Peterson, Eric D.] Duke Univ, Sch Med, Duke Clin Res Inst, Duke Outcomes Res Ctr, Durham, NC USA.
RP Cook, NL (reprint author), 31 Ctr Dr,Bldg 31,Room 5A48, Bethesda, MD 20814 USA.
EM nakela.cook@nih.gov
OI Kressin, Nancy/0000-0003-2767-4286
FU NHLBI [U01HL 105268, U01HL105270, U01HL105342, U01HL107023]; University
of Massachusetts' Clinical and Translational Science Award [U54 RR
026088]; Research Career Scientist award from the Department of Veterans
Affairs, Health Services Research & Development Service [RCS 02-066-1]
FX TRACE-CORE is supported through a cooperative agreement with NHLBI,
U01HL 105268; work on this article is also partially supported through
the University of Massachusetts' Clinical and Translational Science
Award, U54 RR 026088. CCOR at Yale University is supported through a
cooperative agreement with NHLBI, U01HL105270. Center for Health
Insurance Reform, Cardiovascular Outcomes and Disparities is supported
through a cooperative agreement with NHLBI, U01HL105342. Dr Kressin is
supported in part by a Research Career Scientist award from the
Department of Veterans Affairs, Health Services Research & Development
Service (RCS 02-066-1). RCU is supported through a cooperative agreement
with NHLBI, U01HL107023.
NR 23
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U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7705
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD MAR
PY 2013
VL 6
IS 2
BP 223
EP 228
DI 10.1161/CIRCOUTCOMES.0b013e31828e8d5c
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 150LO
UT WOS:000319392100015
PM 23481526
ER
PT J
AU Summers, FA
Mason, RP
Ehrenshaft, M
AF Summers, Fiona A.
Mason, Ronald P.
Ehrenshaft, Marilyn
TI Development of immunoblotting techniques for DNA radical detection
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Free radicals; Oxidatively generated damage; DNA; ELISA; Immuno-spin
trapping; Immunoblotting
ID HYDROGEN-PEROXIDE; PVDF MEMBRANE; GENOMIC DNA; DAMAGE; ION; OXIDATION;
COPPER; BINDING; REQUIREMENT; GLUTATHIONE
AB Radical damage to DNA has been implicated in cell death, cellular dysfunction, and cancer. A recently developed method for detecting DNA radicals uses the nitrone spin trap DMPO (5,5-dimethyl-1-pyrroline N-oxide) to trap radicals. The trapped radicals then decay into stable nitrone adducts detectable with anti-DMPO antibodies and quantifiable by ELISA or dot-blot assay. However, the sequences of DNA that are damaged are likely to be as important as the total level of damage. Therefore, we have developed immunoblotting methods for detection of DNA nitrone adducts on electrophoretically separated DNA, comparable to Western blotting for proteins. These new techniques not only allow the assessment of relative radical adduct levels, but can reveal specific DNA fragments, and ultimately nucleotides, as radical targets. Moreover, we have determined that denaturation of samples into single-stranded DNA enhances the detection of DNA-DMPO adducts in our new blotting methods and also in ELISA. Published by Elsevier Inc.
C1 [Summers, Fiona A.; Mason, Ronald P.; Ehrenshaft, Marilyn] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP Summers, FA (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM summersfa@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Environmental Health Sciences 52 [Z01
ES050139-13]; National Institute of Environmental Health Sciences
FX We are grateful to A.G. Motten, J. Corbett, and M. Mason for valuable
help in the preparation of the manuscript. This work was supported by
the Intramural Research Program of the National Institutes of Health and
the National Institute of Environmental Health Sciences 52 (Z01
ES050139-13). Funding for open access charge was from the Intramural
Research Program of the National Institutes of Health and the National
Institute of Environmental Health Sciences.
NR 48
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Z9 5
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD MAR
PY 2013
VL 56
BP 64
EP 71
DI 10.1016/j.freeradbiomed.2012.10.550
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 154BY
UT WOS:000319647700007
PM 23142572
ER
PT J
AU Wehr, NB
Levine, RL
AF Wehr, Nancy B.
Levine, Rodney L.
TI Antibodies against methionine sulfoxide of proteins Response
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Letter
C1 [Wehr, Nancy B.; Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
RP Levine, RL (reprint author), NIH, Bldg 50,Room 2351, Bethesda, MD 20892 USA.
EM rlevine@nih.gov
RI Levine, Rodney/D-9885-2011
FU Intramural NIH HHS [ZIA HL000225-35]
NR 3
TC 1
Z9 2
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD MAR
PY 2013
VL 56
BP 236
EP 236
DI 10.1016/j.freeradbiomed.2012.12.018
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 154BY
UT WOS:000319647700021
PM 23277145
ER
PT J
AU Kapoor, A
Simmonds, P
Scheel, TKH
Hjelle, B
Cullen, JM
Burbelo, PD
Chauhan, LV
Duraisamy, R
Leon, MS
Jain, K
Vandegrift, KJ
Calisher, CH
Rice, CM
Lipkin, WI
AF Kapoor, Amit
Simmonds, Peter
Scheel, Troels K. H.
Hjelle, Brian
Cullen, John M.
Burbelo, Peter D.
Chauhan, Lokendra V.
Duraisamy, Raja
Leon, Maria Sanchez
Jain, Komal
Vandegrift, Kurt Jason
Calisher, Charles H.
Rice, Charles M.
Lipkin, W. Ian
TI Identification of Rodent Homologs of Hepatitis C Virus and Pegiviruses
SO MBIO
LA English
DT Article
ID SURROGATE MODEL; CELL-CULTURE; INFECTION; REPLICATION; GENOMES; AGENT;
HOST; PATHOGENESIS; NUCLEOTIDE; FLAVIVIRUS
AB Hepatitis C virus (HCV) and human pegivirus (HPgV or GB virus C) are globally distributed and infect 2 to 5% of the human population. The lack of tractable-animal models for these viruses, in particular for HCV, has hampered the study of infection, transmission, virulence, immunity, and pathogenesis. To address this challenge, we searched for homologous viruses in small mammals, including wild rodents. Here we report the discovery of several new hepaciviruses (HCV-like viruses) and pegiviruses (GB virus-like viruses) that infect wild rodents. Complete genome sequences were acquired for a rodent hepacivirus (RHV) found in Peromyscus maniculatus and a rodent pegivirus (RPgV) found in Neotoma albigula. Unique genomic features and phylogenetic analyses confirmed that these RHV and RPgV variants represent several novel virus species in the Hepacivirus and Pegivirus genera within the family Flaviviridae. The genetic diversity of the rodent hepaciviruses exceeded that observed for hepaciviruses infecting either humans or non-primates, leading to new insights into the origin, evolution, and host range of hepaciviruses. The presence of genes, encoded proteins, and translation elements homologous to those found in human hepaciviruses and pegiviruses suggests the potential for the development of new animal systems with which to model HCV pathogenesis, vaccine design, and treatment.
IMPORTANCE The genetic and biological characterization of animal homologs of human viruses provides insights into the origins of human infections and enhances our ability to study their pathogenesis and explore preventive and therapeutic interventions. Horses are the only reported host of nonprimate homologs of hepatitis C virus (HCV). Here, we report the discovery of HCV-like viruses in wild rodents. The majority of HCV-like viruses were found in deer mice (Peromyscus maniculatus), a small rodent used in laboratories to study viruses, including hantaviruses. We also identified pegiviruses in rodents that are distinct from the pegiviruses found in primates, bats, and horses. These novel viruses may enable the development of small-animal models for HCV, the most common infectious cause of liver failure and hepatocellular carcinoma after hepatitis B virus, and help to explore the health relevance of the highly prevalent human pegiviruses.
C1 [Kapoor, Amit; Chauhan, Lokendra V.; Duraisamy, Raja; Leon, Maria Sanchez; Jain, Komal; Calisher, Charles H.; Lipkin, W. Ian] Columbia Univ, Ctr Infect & Immun, New York, NY 10027 USA.
[Simmonds, Peter] Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland.
[Scheel, Troels K. H.; Rice, Charles M.] Rockefeller Univ, Ctr Study Hepatitis C, Lab Virol & Infect Dis, New York, NY 10021 USA.
[Scheel, Troels K. H.] Copenhagen Univ Hosp, Copenhagen Hepatitis C Program CO HEP, Dept Infect Dis, Hvidovre, Denmark.
[Scheel, Troels K. H.] Copenhagen Univ Hosp, Clin Res Ctr, Hvidovre, Denmark.
[Scheel, Troels K. H.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark.
[Hjelle, Brian] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA.
[Cullen, John M.] North Carolina Coll Vet Med, Raleigh, NC USA.
[Burbelo, Peter D.] Natl Inst Dent & Craniofacial Res, Clin Dent Res Core, NIH, Bethesda, MD USA.
[Vandegrift, Kurt Jason] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
RP Kapoor, A (reprint author), Columbia Univ, Ctr Infect & Immun, New York, NY 10027 USA.
EM ak3117@columbia.edu
FU National Institutes of Health [AI081132, AI079231, AI57158, AI070411,
AI090055, AI072613, CA057973, EY017404]; intramural research program,
National Institute of Dental and Craniofacial Research, NIH; Greenberg
Medical Research Institute; Starr Foundation; Danish Council for
Independent Research
FX This work was supported by awards from the National Institutes of Health
(grants AI081132, AI079231, AI57158, AI070411, AI090055, AI072613,
CA057973, and EY017404) and in part from the intramural research
program, National Institute of Dental and Craniofacial Research, NIH,
the Greenberg Medical Research Institute, the Starr Foundation, and the
Danish Council for Independent Research.
NR 39
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U1 2
U2 27
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD MAR-APR
PY 2013
VL 4
IS 2
AR e00216-13
DI 10.1128/mBio.00216-13
PG 10
WC Microbiology
SC Microbiology
GA 137JI
UT WOS:000318431500033
PM 23572554
ER
PT J
AU Tanaka, TQ
Dehdashti, SJ
Nguyen, DT
Mckew, JC
Zheng, W
Williamson, KC
AF Tanaka, Takeshi Q.
Dehdashti, Seameen J.
Dac-Trung Nguyen
McKew, John C.
Zheng, Wei
Williamson, Kim C.
TI A quantitative high throughput assay for identifying gametocytocidal
compounds
SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY
LA English
DT Article
DE Malaria; Gametocytes; AlamarBlue; High throughput screening; Malaria
drug discovery
ID PLASMODIUM-FALCIPARUM GAMETOCYTES; IN-VITRO; MALARIA; CLOTRIMAZOLE;
MEFLOQUINE; REVEALS; DRUGS
AB Current antimalarial drug treatment does not effectively kill mature Plasmodium falciparum gametocytes, the parasite stage responsible for malaria transmission from human to human via a mosquito. Consequently, following standard therapy malaria can still be transmitted for over a week after the clearance of asexual parasites. A new generation of malaria drugs with gametocytocidal properties, or a gametocytocidal drug that could be used in combinational therapy with currently available antimalarials, is needed to control the spread of the disease and facilitate eradication efforts. We have developed a 1536-well gametocyte viability assay for the high throughput screening of large compound collections to identify novel compounds with gametocytocidal activity. The signal-to-basal ratio and Z'-factor for this assay were 3.2-fold and 0.68, respectively. The IC50 value of epoxomicin, the positive control compound, was 1.42 +/- 0.09 nM that is comparable to previously reported values. This miniaturized assay significantly reduces the number of gametocytes required for the AlamarBlue viability assay, and enables high throughput screening for lead discovery efforts. Additionally, the screen does not require a specialized parasite line, gametocytes from any strain, including field isolates, can be tested. A pilot screen utilizing the commercially available LOPAC library, consisting of 1280 known compounds, revealed two selective gametocytocidal compounds having 54- and 7.8-fold gametocytocidal selectivity in comparison to their cell cytotoxicity effect against the mammalian SH-SY5Y cell line. Published by Elsevier B.V.
C1 [Tanaka, Takeshi Q.; Williamson, Kim C.] NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA.
[Dehdashti, Seameen J.; Dac-Trung Nguyen; McKew, John C.; Zheng, Wei] NIH, Natl Ctr Advancing Translat Sci, Bethesda, MD 20892 USA.
[Williamson, Kim C.] Loyola Univ, Dept Biol, Chicago, IL 60660 USA.
RP Zheng, W (reprint author), NIH, Natl Ctr Advancing Translat Sci, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA.
EM wzheng@mail.nih.gov; kwilli4@luc.edu
RI Zheng, Wei/J-8889-2014
OI Zheng, Wei/0000-0003-1034-0757
FU Intramural Research Programs of the Therapeutics for Rare and Neglected
Diseases (TRND), National Center for Advancing Translational Sciences
(NCATS); National Institute of Allergy and Infectious Diseases (NIAID);
Public Health Service from the NIAID, National Institutes of Health
(NIH) [AI10139601]
FX This work was supported by the Intramural Research Programs of the
Therapeutics for Rare and Neglected Diseases (TRND), National Center for
Advancing Translational Sciences (NCATS) and the National Institute of
Allergy and Infectious Diseases (NIAID), and Public Health Service grant
AI10139601 from the NIAID, National Institutes of Health (NIH). The
authors thank Paul Shinn for assistance in compound management. TQT is a
JSPS Research Fellow in Biomedical and Behavioral Research at NIH.
NR 23
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Z9 24
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-6851
J9 MOL BIOCHEM PARASIT
JI Mol. Biochem. Parasitol.
PD MAR
PY 2013
VL 188
IS 1
BP 20
EP 25
DI 10.1016/j.molbiopara.2013.02.005
PG 6
WC Biochemistry & Molecular Biology; Parasitology
SC Biochemistry & Molecular Biology; Parasitology
GA 148LN
UT WOS:000319246200003
PM 23454872
ER
PT J
AU Lee, JG
Baek, K
Soetandyo, N
Ye, YH
AF Lee, Jin-Gu
Baek, Kheewoong
Soetandyo, Nia
Ye, Yihong
TI Reversible inactivation of deubiquitinases by reactive oxygen species in
vitro and in cells
SO NATURE COMMUNICATIONS
LA English
DT Article
ID TYROSINE-PHOSPHATASE 1B; FANCONI-ANEMIA PATHWAY; OXIDATIVE STRESS;
MONOUBIQUITINATED PCNA; REDOX REGULATION; DNA-DAMAGE; UBIQUITIN;
ENZYMES; ROLES; ACTIVATION
AB In eukaryotes, deubiquitinases (DUBs) remove ubiquitin conjugates from diverse substrates, altering their stabilities, localizations or activities. Here we show that many DUBs of the USP and UCH subfamilies can be reversibly inactivated upon oxidation by reactive oxygen species in vitro and in cells. Oxidation occurs preferentially on the catalytic cysteine, abrogating the isopeptide-cleaving activity without affecting these enzymes' affinity to ubiquitin. Sensitivity to oxidative inhibition is associated with DUB activation wherein the active site cysteine is converted to a deprotonated state prone to oxidation. We demonstrate that this redox regulation is essential for mono-ubiquitination of proliferating-cell nuclear antigen in response to oxidative DNA damage, which initiates a DNA damage-tolerance programme. These findings establish a novel mechanism of DUB regulation that may be integrated with other redox-dependent signalling circuits to govern cellular adaptation to oxidative stress, a process intimately linked to aging and cancer.
C1 [Lee, Jin-Gu; Baek, Kheewoong; Soetandyo, Nia; Ye, Yihong] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Ye, YH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM yihongy@mail.nih.gov
FU NIDDK
FX We thank W. Kim and S. Gygi (Harvard Taplin Mass Spectrometry Center)
for assistance in mass spectrometry analyses, J.W. Harper (Harvard
Medical School) and K. Lindsten (Karolinska Institute) for DUB
constructs, K.-Y. Lee (NHGRI) for the USP1 and UAF1 plasmids, J. Kwon
and T. Leto (NIAID) for helpful discussions, M. Krause, M. Gellert
(NIDDK) and Q. Ran (University of Texas Health Science Centre at San
Antonio), and J. Wang (Johns Hopkins University) for critical reading of
the manuscript. The research is supported by the Intramural Research
Program of the NIDDK.
NR 55
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U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2013
VL 4
AR 1568
DI 10.1038/ncomms2532
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 143NJ
UT WOS:000318873900022
PM 23463011
ER
PT J
AU Permuth-Wey, J
Lawrenson, K
Shen, HC
Velkova, A
Tyrer, JP
Chen, ZH
Lin, HY
Chen, YA
Tsai, YY
Qu, XT
Ramus, SJ
Karevan, R
Lee, J
Lee, N
Larson, MC
Aben, KK
Anton-Culver, H
Antonenkova, N
Antoniou, AC
Armasu, SM
Bacot, F
Baglietto, L
Bandera, EV
Barnholtz-Sloan, J
Beckmann, MW
Birrer, MJ
Bloom, G
Bogdanova, N
Brinton, LA
Brooks-Wilson, A
Brown, R
Butzow, R
Cai, QY
Campbell, I
Chang-Claude, J
Chanock, S
Chenevix-Trench, G
Cheng, JQ
Cicek, MS
Coetzee, GA
Cook, LS
Couch, FJ
Cramer, DW
Cunningham, JM
Dansonka-Mieszkowska, A
Despierre, E
Doherty, JA
Dork, T
du Bois, A
Durst, M
Easton, DF
Eccles, D
Edwards, R
Ekici, AB
Fasching, PA
Fenstermacher, DA
Flanagan, JM
Garcia-Closas, M
Gentry-Maharaj, A
Giles, GG
Glasspool, RM
Gonzalez-Bosquet, J
Goodman, MT
Gore, M
Gorski, B
Gronwald, J
Hall, P
Halle, MK
Harter, P
Heitz, F
Hillemanns, P
Hoatlin, M
Hogdall, CK
Hogdall, E
Hosono, S
Jakubowska, A
Jensen, A
Jim, H
Kalli, KR
Karlan, BY
Kaye, SB
Kelemen, LE
Kiemeney, LA
Kikkawa, F
Konecny, GE
Krakstad, C
Kjaer, SK
Kupryjanczyk, J
Lambrechts, D
Lambrechts, S
Lancaster, JM
Le, ND
Leminen, A
Levine, DA
Liang, D
Lim, BK
Lin, J
Lissowska, J
Lu, KH
Lubinski, J
Lurie, G
Massuger, LFAG
Matsuo, K
McGuire, V
McLaughlin, JR
Menon, U
Modugno, F
Moysich, KB
Nakanishi, T
Narod, SA
Nedergaard, L
Ness, RB
Nevanlinna, H
Nickels, S
Noushmehr, H
Odunsi, K
Olson, SH
Orlow, I
Paul, J
Pearce, CL
Pejovic, T
Pelttari, LM
Pike, MC
Poole, EM
Raska, P
Renner, SP
Risch, HA
Rodriguez-Rodriguez, L
Rossing, MA
Rudolph, A
Runnebaum, IB
Rzepecka, IK
Salvesen, HB
Schwaab, I
Severi, G
Shridhar, V
Shu, XO
Shvetsov, YB
Sieh, W
Song, HL
Southey, MC
Spiewankiewicz, B
Stram, D
Sutphen, R
Teo, SH
Terry, KL
Tessier, DC
Thompson, PJ
Tworoger, SS
van Altena, AM
Vergote, I
Vierkant, RA
Vincent, D
Vitonis, AF
Wang-Gohrke, S
Weber, RP
Wentzensen, N
Whittemore, AS
Wik, E
Wilkens, LR
Winterhoff, B
Woo, YL
Wu, AH
Xiang, YB
Yang, HP
Zheng, W
Ziogas, A
Zulkifli, F
Phelan, CM
Iversen, E
Schildkraut, JM
Berchuck, A
Fridley, BL
Goode, EL
Pharoah, PDP
Monteiro, ANA
Sellers, TA
Gayther, SA
AF Permuth-Wey, Jennifer
Lawrenson, Kate
Shen, Howard C.
Velkova, Aneliya
Tyrer, Jonathan P.
Chen, Zhihua
Lin, Hui-Yi
Chen, Y. Ann
Tsai, Ya-Yu
Qu, Xiaotao
Ramus, Susan J.
Karevan, Rod
Lee, Janet
Lee, Nathan
Larson, Melissa C.
Aben, Katja K.
Anton-Culver, Hoda
Antonenkova, Natalia
Antoniou, Antonis C.
Armasu, Sebastian M.
Bacot, Francois
Baglietto, Laura
Bandera, Elisa V.
Barnholtz-Sloan, Jill
Beckmann, Matthias W.
Birrer, Michael J.
Bloom, Greg
Bogdanova, Natalia
Brinton, Louise A.
Brooks-Wilson, Angela
Brown, Robert
Butzow, Ralf
Cai, Qiuyin
Campbell, Ian
Chang-Claude, Jenny
Chanock, Stephen
Chenevix-Trench, Georgia
Cheng, Jin Q.
Cicek, Mine S.
Coetzee, Gerhard A.
Cook, Linda S.
Couch, Fergus J.
Cramer, Daniel W.
Cunningham, Julie M.
Dansonka-Mieszkowska, Agnieszka
Despierre, Evelyn
Doherty, Jennifer A.
Doerk, Thilo
du Bois, Andreas
Duerst, Matthias
Easton, Douglas F.
Eccles, Diana
Edwards, Robert
Ekici, Arif B.
Fasching, Peter A.
Fenstermacher, David A.
Flanagan, James M.
Garcia-Closas, Montserrat
Gentry-Maharaj, Aleksandra
Giles, Graham G.
Glasspool, Rosalind M.
Gonzalez-Bosquet, Jesus
Goodman, Marc T.
Gore, Martin
Gorski, Bohdan
Gronwald, Jacek
Hall, Per
Halle, Mari K.
Harter, Philipp
Heitz, Florian
Hillemanns, Peter
Hoatlin, Maureen
Hogdall, Claus K.
Hogdall, Estrid
Hosono, Satoyo
Jakubowska, Anna
Jensen, Allan
Jim, Heather
Kalli, Kimberly R.
Karlan, Beth Y.
Kaye, Stanley B.
Kelemen, Linda E.
Kiemeney, Lambertus A.
Kikkawa, Fumitaka
Konecny, Gottfried E.
Krakstad, Camilla
Kjaer, Susanne Kruger
Kupryjanczyk, Jolanta
Lambrechts, Diether
Lambrechts, Sandrina
Lancaster, Johnathan M.
Le, Nhu D.
Leminen, Arto
Levine, Douglas A.
Liang, Dong
Lim, Boon Kiong
Lin, Jie
Lissowska, Jolanta
Lu, Karen H.
Lubinski, Jan
Lurie, Galina
Massuger, Leon F. A. G.
Matsuo, Keitaro
McGuire, Valerie
McLaughlin, John R.
Menon, Usha
Modugno, Francesmary
Moysich, Kirsten B.
Nakanishi, Toru
Narod, Steven A.
Nedergaard, Lotte
Ness, Roberta B.
Nevanlinna, Heli
Nickels, Stefan
Noushmehr, Houtan
Odunsi, Kunle
Olson, Sara H.
Orlow, Irene
Paul, James
Pearce, Celeste L.
Pejovic, Tanja
Pelttari, Liisa M.
Pike, Malcolm C.
Poole, Elizabeth M.
Raska, Paola
Renner, Stefan P.
Risch, Harvey A.
Rodriguez-Rodriguez, Lorna
Rossing, Mary Anne
Rudolph, Anja
Runnebaum, Ingo B.
Rzepecka, Iwona K.
Salvesen, Helga B.
Schwaab, Ira
Severi, Gianluca
Shridhar, Viji
Shu, Xiao-Ou
Shvetsov, Yurii B.
Sieh, Weiva
Song, Honglin
Southey, Melissa C.
Spiewankiewicz, Beata
Stram, Daniel
Sutphen, Rebecca
Teo, Soo-Hwang
Terry, Kathryn L.
Tessier, Daniel C.
Thompson, Pamela J.
Tworoger, Shelley S.
van Altena, Anne M.
Vergote, Ignace
Vierkant, Robert A.
Vincent, Daniel
Vitonis, Allison F.
Wang-Gohrke, Shan
Weber, Rachel Palmieri
Wentzensen, Nicolas
Whittemore, Alice S.
Wik, Elisabeth
Wilkens, Lynne R.
Winterhoff, Boris
Woo, Yin Ling
Wu, Anna H.
Xiang, Yong-Bing
Yang, Hannah P.
Zheng, Wei
Ziogas, Argyrios
Zulkifli, Famida
Phelan, Catherine M.
Iversen, Edwin
Schildkraut, Joellen M.
Berchuck, Andrew
Fridley, Brooke L.
Goode, Ellen L.
Pharoah, Paul D. P.
Monteiro, Alvaro N. A.
Sellers, Thomas A.
Gayther, Simon A.
CA Australian Canc Study
Australian Ovarian Canc Study
Consortium Investigators Modifiers
TI Identification and molecular characterization of a new ovarian cancer
susceptibility locus at 17q21.31
SO NATURE COMMUNICATIONS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MICRORNA EXPRESSION; GENETIC-VARIANTS;
FUNCTIONAL ANNOTATION; SITE POLYMORPHISMS; PARKINSON-DISEASE; COMMON
INVERSION; BINDING-SITES; MAPT REGION; RISK
AB Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio 1.12, P 10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P 10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARH-GAP27 and PLEKHM1 as candidate EOC susceptibility genes.
C1 [Permuth-Wey, Jennifer; Velkova, Aneliya; Tsai, Ya-Yu; Phelan, Catherine M.; Monteiro, Alvaro N. A.; Sellers, Thomas A.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Div Populat Sci, Tampa, FL 33612 USA.
[Lawrenson, Kate; Shen, Howard C.; Ramus, Susan J.; Karevan, Rod; Lee, Janet; Lee, Nathan; Pearce, Celeste L.; Pike, Malcolm C.; Stram, Daniel; Wu, Anna H.; Gayther, Simon A.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Tyrer, Jonathan P.; Song, Honglin] Univ Cambridge, Dept Oncol, Cambridge CB1 8RN, England.
[Chen, Zhihua; Qu, Xiaotao; Bloom, Greg; Fenstermacher, David A.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Biomed Informat, Tampa, FL 33612 USA.
[Lin, Hui-Yi; Chen, Y. Ann] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Biostat, Tampa, FL 33612 USA.
[Larson, Melissa C.; Armasu, Sebastian M.; Vierkant, Robert A.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
[Aben, Katja K.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & HTA, NL-6500 HB Nijmegen, Netherlands.
[Aben, Katja K.; Kiemeney, Lambertus A.] Comprehens Canc Ctr Netherlands, NL-1066 CX Amsterdam, Netherlands.
[Anton-Culver, Hoda] Univ Calif Irvine, UCI Ctr Med, Genet Epidemiol Res Inst, Dept Epidemiol, Irvine, CA 92697 USA.
[Antonenkova, Natalia] Byelorussian Inst Oncol & Med Radiol Aleksandrov, Minsk 223040, Byelarus.
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[Chenevix-Trench, Georgia] Queensland Inst Med Res, Canc Genet Lab, Brisbane, Qld 4006, Australia.
[Campbell, Ian] Peter MacCallum Canc Ctr, Div Res, Melbourne, Vic 3002, Australia.
[Bacot, Francois; Tessier, Daniel C.; Vincent, Daniel] McGill Univ, Montreal, PQ H3A 0G1, Canada.
[Bacot, Francois; Tessier, Daniel C.; Vincent, Daniel] Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.
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[Bandera, Elisa V.; Rodriguez-Rodriguez, Lorna] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ 08901 USA.
[Barnholtz-Sloan, Jill; Raska, Paola] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA.
[Beckmann, Matthias W.; Fasching, Peter A.; Renner, Stefan P.] Univ Erlangen Nurnberg, Ctr Comprehens Canc, Univ Hosp Erlangen, Dept Gynecol & Obstet, D-91054 Erlangen, Germany.
[Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Bogdanova, Natalia; Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, D-30625 Hannover, Germany.
[Brinton, Louise A.; Chanock, Stephen; Wentzensen, Nicolas; Yang, Hannah P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Brooks-Wilson, Angela] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
[Brown, Robert; Flanagan, James M.] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London SW7 2AZ, England.
[Butzow, Ralf; Leminen, Arto] Univ Helsinki, Dept Obstet & Gynecol, HUS, FIN-00290 Helsinki, Finland.
[Butzow, Ralf; Leminen, Arto] Univ Helsinki, Cent Hosp, HUS, FIN-00290 Helsinki, Finland.
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[Campbell, Ian] Univ Melbourne, Dept Pathol, Melbourne, Vic 3053, Australia.
[Chang-Claude, Jenny; Nickels, Stefan; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
[Cheng, Jin Q.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA.
[Cicek, Mine S.; Goode, Ellen L.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN 55905 USA.
[Coetzee, Gerhard A.; Noushmehr, Houtan] Univ So Calif, Norris Comprehens Canc Ctr, Dept Urol Microbiol & Prevent Med, Los Angeles, CA 90089 USA.
[Cook, Linda S.] Univ New Mexico, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA.
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[Cramer, Daniel W.; Terry, Kathryn L.; Vitonis, Allison F.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA.
[Cramer, Daniel W.; Terry, Kathryn L.; Vitonis, Allison F.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Cunningham, Julie M.; Shridhar, Viji] Mayo Clin, Dept Lab Med & Pathol, Div Expt Pathol, Rochester, MN 55905 USA.
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[Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Rzepecka, Iwona K.; Spiewankiewicz, Beata] Inst Oncol, PL-02781 Warsaw, Poland.
[Despierre, Evelyn; Lambrechts, Sandrina; Vergote, Ignace] Univ Hosp Leuven, Dept Obstet & Gynaecol, Div Gynecol Oncol, B-3000 Louvain, Belgium.
[Despierre, Evelyn; Lambrechts, Sandrina; Vergote, Ignace] Univ Hosp Leuven, Leuven Canc Inst, B-3000 Louvain, Belgium.
[Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Epidemiol & Biostat Sect, Lebanon, NH 03755 USA.
[du Bois, Andreas; Harter, Philipp; Heitz, Florian] Dr Horst Schmidt Klin, Dept Gynecol & Gynecol Oncol, D-65199 Wiesbaden, Germany.
[du Bois, Andreas; Harter, Philipp; Heitz, Florian] Kliniken Essen Mitte, Dept Gynecol & Gynecol Oncol, D-45136 Essen, Germany.
[Duerst, Matthias; Runnebaum, Ingo B.; Pharoah, Paul D. P.] Jena Univ Hosp, Dept Gynecol & Obstet, D-07743 Jena, Germany.
[Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge CB1 8RN, England.
[Eccles, Diana] Univ Southampton, Southampton Univ Hosp, Fac Med, Southampton SO17 1BJ, Hants, England.
[Edwards, Robert] Maggee Womens Hosp, Pittsburgh, PA 15213 USA.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, D-91054 Erlangen, Germany.
[Fasching, Peter A.; Konecny, Gottfried E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Garcia-Closas, Montserrat] Inst Canc Res, Epidemiol Sect, London SW7 3RP, England.
[Garcia-Closas, Montserrat] Inst Canc Res, Genet Sect, London SW7 3RP, England.
[Garcia-Closas, Montserrat] Breakthrough Breast Canc Res Ctr, London SW7 3RP, England.
[Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, Inst Womens Hlth, Gynaecol Canc Res Ctr, London W1T 7DN, England.
[Giles, Graham G.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3806, Australia.
[Glasspool, Rosalind M.; Paul, James] Beatson West Scotland Canc Ctr, Glasgow G12 0YN, Lanark, Scotland.
[Gonzalez-Bosquet, Jesus; Lancaster, Johnathan M.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Womens Oncol, Tampa, FL 33612 USA.
[Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Gore, Martin] Royal Marsden Hosp, Gynecol Oncol Unit, London SW3 6JJ, England.
[Gorski, Bohdan; Gronwald, Jacek; Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, PL-70115 Szczecin, Poland.
[Hall, Per] Karolinska Ist, Dept Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Halle, Mari K.; Krakstad, Camilla; Salvesen, Helga B.; Wik, Elisabeth] Haukeland Hosp, Dept Gynecol & Obstet, N-5006 Bergen, Norway.
[Halle, Mari K.; Krakstad, Camilla; Salvesen, Helga B.; Wik, Elisabeth] Univ Bergen, Dept Clin Sci, N-5006 Bergen, Norway.
[Hillemanns, Peter] Hannover Med Sch, Clin Obstet, D-30625 Hannover, Germany.
[Hillemanns, Peter] Hannover Med Sch, Clin Gynaecol, D-30625 Hannover, Germany.
[Hoatlin, Maureen] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA.
[Hogdall, Claus K.; Kjaer, Susanne Kruger] Rigshosp, Juliane Marie Ctr, Dept Obstet & Gynecol, DK-2100 Copenhagen, Denmark.
[Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Mol Unit, Dept Pathol, DK-2730 Herlev, Denmark.
[Hogdall, Estrid; Jensen, Allan; Kjaer, Susanne Kruger] Danish Canc Soc, Res Ctr, DK-2100 Copenhagen, Denmark.
[Hosono, Satoyo; Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 4648681, Japan.
[Jim, Heather] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Hlth Outcomes & Behav, Tampa, FL 33612 USA.
[Kalli, Kimberly R.] Mayo Clin, Dept Med Oncol, Rochester, MN 55905 USA.
[Karlan, Beth Y.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
[Kaye, Stanley B.] Inst Canc Res, Med Sect, Sutton SM2 5NG, Surrey, England.
[Kelemen, Linda E.] Alberta Hlth Serv Canc Care, Dept Popluat Hlth Res, Calgary, AB, Canada.
[Kelemen, Linda E.] Univ Calgary, Dept Med Genet, Calgary, AB T2S 3C3, Canada.
[Kelemen, Linda E.] Univ Calgary, Dept Oncol, Calgary, AB T2S 3C3, Canada.
[Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6500 HB Nijmegen, Netherlands.
[Kikkawa, Fumitaka] Nagoya Univ, Grad Sch Med, Dept Obster & Gynecol, Nagoya, Aichi 4668550, Japan.
[Lambrechts, Diether] VIB, Vesalius Res Ctr, B-3000 Louvain, Belgium.
[Lambrechts, Diether] Univ Louvain, Dept Oncol, Lab Translat Genet, B-3000 Louvain, Belgium.
[Le, Nhu D.] BC Canc Agcy, Vancouver, BC G12 0YN, Canada.
[Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA.
[Liang, Dong] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77004 USA.
[Lim, Boon Kiong; Woo, Yin Ling] Univ Malaya, Fac Med, UM Canc Res Inst, Dept Obstet & Gynaecol, Kuala Lumpur 59100, Malaysia.
[Lin, Jie] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland.
[Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
[Lurie, Galina; Shvetsov, Yurii B.; Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96813 USA.
[Massuger, Leon F. A. G.; van Altena, Anne M.] Radboud Univ Nijmegen, Dept Gynaecol, Med Ctr, NL-6500 HB Nijmegen, Netherlands.
[McGuire, Valerie; Sieh, Weiva; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA.
[McLaughlin, John R.] Univ Toronto, Fac Med, Dalla Lana Sch Publ Hlth, Toronto, ON M5T 3M7, Canada.
[McLaughlin, John R.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Modugno, Francesmary] Magee Womens Res Inst, Womens Canc Res Program, Pittsburgh, PA 15213 USA.
[Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA.
[Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Modugno, Francesmary] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA.
[Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Nakanishi, Toru] Aichi Canc Ctr, Cent Hosp, Dept Gynecol Oncol, Nagoya, Aichi 4648681, Japan.
[Narod, Steven A.] Univ Toronto, Womens Coll Res Inst, Toronto, ON M5G 1N8, Canada.
[Nedergaard, Lotte] Univ Copenhagen, Rigshosp, Dept Pathol, DK-2100 Copenhagen, Denmark.
[Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77030 USA.
[Noushmehr, Houtan] Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, USC Epigenome Ctr, Los Angeles, CA 90089 USA.
[Noushmehr, Houtan] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Genet, BR-14049900 Ribeirao Preto, SP, Brazil.
[Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA.
[Olson, Sara H.; Orlow, Irene; Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
[Pejovic, Tanja] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97239 USA.
[Pejovic, Tanja] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA.
[Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT 06520 USA.
[Risch, Harvey A.] Yale Univ, Sch Med, New Haven, CT 06520 USA.
[Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98109 USA.
[Schwaab, Ira] Inst Human Genet Wiesbaden, D-65187 Wiesbaden, Germany.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic 3053, Australia.
[Spiewankiewicz, Beata] Maria Sklodowska Curie Mem Canc Ctr, Dept Gynecol Oncol, PL-02781 Warsaw, Poland.
[Sutphen, Rebecca] Univ S Florida, Coll Med, Pediat Epidemiol Ctr, Tampa, FL 33612 USA.
[Teo, Soo-Hwang; Zulkifli, Famida] Sime Darby Med Ctr, Canc Res Initiat Fdn, Selangor 47500, Malaysia.
[Teo, Soo-Hwang; Zulkifli, Famida] Univ Malaya, Fac Med, Dept Surg, Kuala Lumpur 59100, Malaysia.
[Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, Sch Med, Channing Div Network Med, Boston, MA 02115 USA.
[Poole, Elizabeth M.; Tworoger, Shelley S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, D-89081 Ulm, Germany.
[Weber, Rachel Palmieri; Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27708 USA.
[Winterhoff, Boris] Mayo Clin, Dept Obstet & Gynecol, Rochester, MN 55905 USA.
[Xiang, Yong-Bing] Shanghai Canc Inst, Shanghai 220025, Peoples R China.
[Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Ctr Canc Genet Res & Prevent, Dept Epidemiol, Irvine, CA 92697 USA.
[Iversen, Edwin] Duke Univ, Dept Stat Sci, Durham, NC 27708 USA.
[Schildkraut, Joellen M.] Duke Canc Inst, Canc Prevent Detect & Control Res Program, Durham, NC 27708 USA.
[Berchuck, Andrew] Duke Canc Inst, Dept Obstet & Gynecol, Durham, NC 27708 USA.
[Fridley, Brooke L.] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66160 USA.
RP Permuth-Wey, J (reprint author), Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Div Populat Sci, Tampa, FL 33612 USA.
EM Jenny.Wey@moffitt.org; Thomas.Sellers@moffitt.org; gayther@usc.edu
RI Whittemore, Alice/F-9925-2014; Brooks-Wilson, Angela/E-9399-2012; Teo,
Soo-hwang/H-2353-2014; Bandera, Elisa/M-4169-2014; Massuger,
Leon/H-8072-2014; friedlander, michael/G-3490-2013; Noushmehr,
Houtan/C-9692-2013; McLaughlin, John/E-4577-2013; Kiemeney,
Lambertus/D-3357-2009; Tang, Macy/B-9798-2014; Blanco,
Ignacio/D-2565-2013; Renner, Stefan/F-1158-2014; Dork,
Thilo/J-8620-2012; salvesen, Helga/C-1187-2017; Osorio, Ana/I-4324-2014;
Wyld, David/B-8893-2015; Jakubowska, Anna/O-8050-2014; campbell,
Ian/F-6006-2011; Fridley, Brooke/D-8315-2015; Garcia-Closas, Montserrat
/F-3871-2015; Brinton, Louise/G-7486-2015; montagna, marco/E-2225-2012;
Woo, Yin Ling/B-5198-2010; KIKKAWA, Fumitaka/I-7341-2014; Nicklin,
James/F-8035-2013; van Altena, Anne/B-9824-2016; Aben,
Katja/G-9686-2016; Bowtell, David/H-1007-2016; Gronwald,
Jacek/A-4576-2017
OI Brooks-Wilson, Angela/0000-0003-1009-6408; Bandera,
Elisa/0000-0002-8789-2755; friedlander, michael/0000-0002-6488-0604;
Noushmehr, Houtan/0000-0003-4051-8114; Kiemeney,
Lambertus/0000-0002-2368-1326; Blanco, Ignacio/0000-0002-7414-7481;
Renner, Stefan/0000-0003-2057-1268; Ramus, Susan/0000-0003-0005-7798;
Lissowska, Jolanta/0000-0003-2695-5799; Nevanlinna,
Heli/0000-0002-0916-2976; Halle, Mari/0000-0002-2660-8271; Orlow,
Irene/0000-0001-6234-6961; Krakstad, Camilla/0000-0002-0174-8139; Giles,
Graham/0000-0003-4946-9099; Matsuo, Keitaro/0000-0003-1761-6314;
salvesen, Helga/0000-0002-4438-8831; Tworoger,
Shelley/0000-0002-6986-7046; Osorio, Ana/0000-0001-8124-3984; Nathanson,
Katherine/0000-0002-6740-0901; Rudolph, Anja/0000-0001-7520-2035; Kjaer,
Susanne/0000-0002-8347-1398; Glasspool, Rosalind/0000-0002-5000-1680;
Wyld, David/0000-0001-9523-4333; Monteiro, Alvaro/0000-0002-8448-4801;
Fridley, Brooke/0000-0001-7739-7956; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; montagna,
marco/0000-0002-4929-2150; Woo, Yin Ling/0000-0003-1742-1066; Nicklin,
James/0000-0001-5378-496X; Aben, Katja/0000-0002-0214-2147; Bowtell,
David/0000-0001-9089-7525; Gronwald, Jacek/0000-0002-3643-2871
FU European Commission [223175-HEALTH-F2-2009-223175]; Ovarian Cancer
Research Fund; US National Cancer Institute [R01-CA-114343,
R01-CA114343-S1]; Genetic Associations and Mechanisms in Oncology
(GAME-ON): a NCI Cancer Post-GWAS Initiative [U19-CA148112]; Wellcome
Trust [076113]; National Health and Medical Research Council; American
Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN];
Canadian Institutes of Health Research [MSH-87734]; NHS; American Cancer
Society [CRTG-00-196-01-CCE]; California Cancer Research Program
[00-01389V-20170, N01-CN25403, 2II0200]; Canadian Institutes for Health
Research [MOP-86727]; Cancer Council Victoria; Cancer Council
Queensland; Cancer Council New South Wales; Cancer Council South
Australia; Cancer Council Tasmania; Cancer Foundation of Western
Australia; Cancer Institute of New Jersey; Cancer Research UK
[C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689]; Celma
Mastry Ovarian Cancer Foundation; Danish Cancer Society [94-222-52];
Norwegian Cancer Society, Helse Vest, the Norwegian Research Council;
ELAN Funds of the University of Erlangen-Nuremberg; Eve Appeal; Helsinki
University Central Hospital Research Fund; Imperial Experimental Cancer
Research Centre [C1312/A15589]; Nationaal Kankerplan of Belgium;
Ministry of Health Labour and Welfare of Japan; L & S Milken Foundation;
Radboud University Nijmegen Medical Centre; Polish Ministry of Science
and Higher Education [4 PO5C 028 14, 2 PO5A 068 27]; Roswell Park Cancer
Institute Alliance Foundation; US National Cancer Institutes
[K07-CA80668, K07-CA095666, K07-CA143047, K22-CA138563, N01-CN55424,
N01-PC067001, N01-PC035137, P01-CA017054, P01-CA087696, P50-CA105009,
P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449,
R01-CA050385, R01-CA054419]; NIH/National Center for Research
Resources/General Clinical Research Grant [M01-RR000056]; US Army
Medical Research and Materiel Command [DAMD17-98-18659,
DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-101-02802];
Department of Defense Ovarian Cancer Research Program
[W81XWH-07-1-0449]; National Health and Medical Research Council of
Australia [199600, 400281]; German Federal Ministry of Education and
Research of Germany Programme of Clinical Biomedical Research [01 GB
9401]; state of Baden-Wurttemberg through Medical Faculty of the
University of Ulm [P.685]; German Cancer Research Center; Pomeranian
Medical University; Minnesota Ovarian Cancer Alliance; Mayo Foundation;
Fred C. and Katherine B. Andersen Foundation; Malaysian Ministry of
Higher Education [UM. C/HlR/MOHE/06]; Cancer Research Initiatives
Foundation; Lon V. Smith Foundation [LVS-39420]; Oak Foundation; OHSU
Foundation; Mermaid I project; Rudolf-Bartling Foundation; UK National
Institute for Health Research Biomedical Research Centres at the
University of Cambridge; Imperial College London; University College
Hospital 'Womens Health Theme'; Royal Marsden Hospital; WorkSafeBC; U.S.
Natl Canc Inst [R01-CA058598, R01-CA058860, R01-CA061107, R01-CA061132,
R01-CA063678, R01-CA063682, R01-CA064277, R01-CA067262, R01-CA071766,
R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA087538,
R01-CA092044, R01-095023, R01-CA106414, R01-CA122443, R01-CA136924,
R01-CA112523, R01-CA114343, R01-CA126841, R01-CA149429, R03-CA113148,
R03-CA115195, R37-CA070867, R01-CA83918, U01-CA069417, U01-CA071966,
P30-CA15083, PSA 042205]
FX We thank all the individuals who participated in this research and all
the researchers, clinicians and administrative staff who have made
possible the many studies contributing to this work. In particular, we
thank D. Bowtell, P. Webb, A. deFazio, D. Gertig, A. Green, P. Parsons,
N. Hayward and D. Whiteman (AUS); D. L. Wachter, S. Oeser, S. Landrith
(BAV); G. Peuteman, T. Van Brussel and D. Smeets (BEL); the staff of the
genotyping unit, S LaBoissiere and F Robidoux (McGill University and
Genome Quebec Innovation Centre); U. Eilber and T. Koehler (GER); L.
Gacucova (HMO); P. Schuermann, F. Kramer, T.-W. Park-Simon, K.
Beer-Grondke and D. Schmidt (HJO); G. L. Keeney, C. Hilker and J.
Vollenweider (MAY); the state cancer registries of AL, AZ, AR, CA, CO,
CT, DE, FL, GA, HI, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ,
NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA and WYL (NHS); L.
Paddock, M. King, U. Chandran, A. Samoila and Y. Bensman (NJO); M. Insua
and R. Evey (Moffitt); The Sherie Hildredth Ovarian Cancer Foundation
(ORE); M. Sherman, A. Hutchinson, N. Szeszenia-Dabrowska, B. Peplonska,
W. Zatonski, A. Soni, P. Chao and M. Stagner (POL); C. Luccarini, P.
Harrington the SEARCH team and ECRIC (SEA); the Scottish Gynaecological
Clinical Trails group and SCOTROC1 investigators (SRO); W-H. Chow, Y.-T.
Gao, G. Yang, B.-T. Ji (SWH); I. Jacobs, M. Widschwendter, E. Wozniak,
N. Balogun, A. Ryan and J. Ford (UKO); M. Notaridou (USC); C. Pye (UKR);
and V. Slusher (U19). The COGS project is funded through a European
Commission's Seventh Framework Programme grant (agreement number
223175-HEALTH-F2-2009-223175). The Ovarian Cancer Association Consortium
is supported by a grant from the Ovarian Cancer Research Fund, thanks to
donations by the family and friends of Kathryn Sladek Smith
(PPD/RPCI.07).; The scientific development and funding for this project
were in part supported by the US National Cancer Institute
(R01-CA-114343 and R01-CA114343-S1) and the Genetic Associations and
Mechanisms in Oncology (GAME-ON): a NCI Cancer Post-GWAS Initiative
(U19-CA148112). This study made use of the data generated by the
Wellcome Trust Case Control consortium. A full list of the investigators
who contributed to the generation of the data is available from
http://www.wtccc.org.uk/. Funding for the project was provided by the
Wellcome Trust under award 076113. The results published here are in
part based upon data generated by The Cancer Genome Atlas Pilot Project
established by the National Cancer Institute and National Human Genome
Research Institute. Information about TCGA, and the investigators and
institutions who constitute the TCGA research network can be found at
http://cancergenome.nih.gov/. D. F. E. is a Principal Research Fellow of
Cancer Research UK, G.C.-T. and P. M. W. are supported by the National
Health and Medical Research Council. B. K. holds an American Cancer
Society Early Detection Professorship (SIOP-06-258-01-COUN). L. E. K. is
supported by a Canadian Institutes of Health Research Investigator award
(MSH-87734). M. G. acknowledges NHS funding to the NIHR Biomedical
Research Centre. A. C. A. is Cancer Research UK Senior Cancer Research
Fellow.; Funding of the constituent studies was provided by the American
Cancer Society (CRTG-00-196-01-CCE); the California Cancer Research
Program (00-01389V-20170, N01-CN25403, 2II0200); the Canadian Institutes
for Health Research (MOP-86727); Cancer Council Victoria; Cancer Council
Queensland; Cancer Council New South Wales; Cancer Council South
Australia; Cancer Council Tasmania; Cancer Foundation of Western
Australia; the Cancer Institute of New Jersey; Cancer Research UK
(C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689); the
Celma Mastry Ovarian Cancer Foundation; the Danish Cancer Society
(94-222-52); the Norwegian Cancer Society, Helse Vest, the Norwegian
Research Council; ELAN Funds of the University of Erlangen-Nuremberg;
the Eve Appeal; the Helsinki University Central Hospital Research Fund;
Imperial Experimental Cancer Research Centre (C1312/A15589); the Ovarian
Cancer Research Fund; Nationaal Kankerplan of Belgium; Grant-in-Aid for
the Third Term Comprehensive 10-Year Strategy for Cancer Control from
the Ministry of Health Labour and Welfare of Japan; the L & S Milken
Foundation; the Radboud University Nijmegen Medical Centre; the Polish
Ministry of Science and Higher Education (4 PO5C 028 14, 2 PO5A 068 27);
the Roswell Park Cancer Institute Alliance Foundation; the US National
Cancer Institute (K07-CA80668, K07-CA095666, K07-CA143047, K22-CA138563,
N01-CN55424, N01-PC067001, N01-PC035137, P01-CA017054, P01-CA087696,
P50-CA105009, P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054,
R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860,
R01-CA061107, R01-CA061132, R01-CA063678, R01-CA063682, R01-CA064277,
R01-CA067262, R01-CA071766, R01-CA074850, R01-CA076016, R01-CA080742,
R01-CA080978, R01-CA087538, R01-CA092044, R01-095023, R01-CA106414,
R01-CA122443, R01-CA136924, R01-CA112523, R01-CA114343, R01-CA126841,
R01-CA149429, R03-CA113148, R03-CA115195, R37-CA070867, R01-CA83918,
U01-CA069417, U01-CA071966, P30-CA15083, PSA 042205, and Intramural
research funds); the NIH/National Center for Research Resources/General
Clinical Research Grant (M01-RR000056); the US Army Medical Research and
Materiel Command (DAMD17-98-18659, DAMD17-01-1-0729, DAMD17-02-1-0666,
DAMD17-02-1-0669, W81XWH-101- 02802); the Department of Defense Ovarian
Cancer Research Program (W81XWH-07-1-0449); the National Health and
Medical Research Council of Australia (199600 and 400281); the German
Federal Ministry of Education and Research of Germany Programme of
Clinical Biomedical Research (01 GB 9401); the state of
Baden-Wurttemberg through Medical Faculty of the University of Ulm (P.
685); the German Cancer Research Center; Pomeranian Medical University;
the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C.
and Katherine B. Andersen Foundation; the Malaysian Ministry of Higher
Education (UM. C/HlR/MOHE/06) and Cancer Research Initiatives
Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak Foundation;
the OHSU Foundation; the Mermaid I project; the Rudolf-Bartling
Foundation; the UK National Institute for Health Research Biomedical
Research Centres at the University of Cambridge, Imperial College
London, University College Hospital 'Womens Health Theme' and the Royal
Marsden Hospital; WorkSafeBC.
NR 53
TC 49
Z9 49
U1 2
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2013
VL 4
AR 1627
DI 10.1038/ncomms2613
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 143NJ
UT WOS:000318873900080
PM 23535648
ER
PT J
AU Rickhag, M
Hansen, FH
Sorensen, G
Strandfelt, KN
Andresen, B
Gotfryd, K
Madsen, KL
Vestergaard-Klewe, I
Ammendrup-Johnsen, I
Eriksen, J
Newman, AH
Fuchtbauer, EM
Gomeza, J
Woldbye, DPD
Wortwein, G
Gether, U
AF Rickhag, Mattias
Hansen, Freja Herborg
Sorensen, Gunnar
Strandfelt, Kristine Norgaard
Andresen, Bjorn
Gotfryd, Kamil
Madsen, Kenneth L.
Vestergaard-Klewe, Ib
Ammendrup-Johnsen, Ina
Eriksen, Jacob
Newman, Amy H.
Fuchtbauer, Ernst-Martin
Gomeza, Jesus
Woldbye, David P. D.
Wortwein, Gitta
Gether, Ulrik
TI A C-terminal PDZ domain-binding sequence is required for striatal
distribution of the dopamine transporter
SO NATURE COMMUNICATIONS
LA English
DT Article
ID MICE LACKING; MONOAMINE TRANSPORTERS; LIGAND MOTIF; LOCALIZATION;
TRAFFICKING; SURFACE; INTERNALIZATION; GLUTAMATE; CELLS; PICK1
AB The dopamine transporter mediates reuptake of dopamine from the synaptic cleft. The cellular mechanisms controlling dopamine transporter levels in striatal nerve terminals remain poorly understood. The dopamine transporters contain a C-terminal PDZ (PSD-95/Discs-large/ZO-1) domain-binding sequence believed to bind synaptic scaffolding proteins, but its functional significance is uncertain. Here we demonstrate that two different dopamine transporter knock-in mice with disrupted PDZ-binding motifs (dopamine transporter-AAA and dopamine transporter + Ala) are characterized by dramatic loss of dopamine transporter expression in the striatum, causing hyperlocomotion and attenuated response to amphetamine. In cultured dopaminergic neurons and striatal slices from dopamine transporter-AAA mice, we find markedly reduced dopamine transporter surface levels and evidence for enhanced constitutive internalization. In dopamine transporter-AAA neurons, but not in wildtype neurons, surface levels are rescued in part by expression of a dominant-negative dynamin mutation (K44A). Our findings suggest that PDZ-domain interactions are critical for synaptic distribution of dopamine transporter in vivo and thereby for proper maintenance of dopamine homoeostasis.
C1 [Rickhag, Mattias; Hansen, Freja Herborg; Sorensen, Gunnar; Strandfelt, Kristine Norgaard; Andresen, Bjorn; Gotfryd, Kamil; Madsen, Kenneth L.; Vestergaard-Klewe, Ib; Ammendrup-Johnsen, Ina; Eriksen, Jacob; Gether, Ulrik] Univ Copenhagen, Fac Hlth & Med Sci, Lundbeck Fdn Ctr Biomembranes Nanomed, Dept Neurosci & Pharmacol,Mol Neuropharmacol Lab, Copenhagen, Denmark.
[Sorensen, Gunnar; Woldbye, David P. D.; Wortwein, Gitta] Univ Copenhagen, Fac Hlth & Med Sci, Dept Neurosci & Pharmacol, Lab Neuropsychiat, Copenhagen, Denmark.
[Newman, Amy H.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Fuchtbauer, Ernst-Martin] Aarhus Univ, Dept Mol Biol, DK-8000 Aarhus, Denmark.
[Gomeza, Jesus] Univ Bonn, Inst Pharmaceut Biol, Bonn, Germany.
[Wortwein, Gitta] Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark.
RP Gether, U (reprint author), Univ Copenhagen, Fac Hlth & Med Sci, Lundbeck Fdn Ctr Biomembranes Nanomed, Dept Neurosci & Pharmacol,Mol Neuropharmacol Lab, Copenhagen, Denmark.
EM gether@sund.ku.dk
RI Madsen, Kenneth/C-7778-2012;
OI Madsen, Kenneth/0000-0001-9274-6691; Eriksen, Jacob/0000-0003-0726-9769;
Gether, Ulrik/0000-0002-0020-3807; Wortwein, Gitta/0000-0001-6981-7885
FU National Institute of Health [P01 DA 12408]; Danish Medical Research
Council; University of Copenhagen BioScaRT Program of Excellence;
Lundbeck Foundation Center for Biomembranes in Nanomedicine; Lundbeck
Foundation; Novo Nordisk Foundation; Fabrikant Vilhelm Pedersen og
Hustrus Mindelegat
FX We thank P. Elsman, P. Clausen and L. A. Hansen for excellent technical
assistance and A. Fuchtbauer for ES cell culture. We thank Professor M.
Moller for comments on the manuscript. The work was supported by the
National Institute of Health Grants P01 DA 12408 (U. G.), the Danish
Medical Research Council (M. R., K. L. M., B. A. and U. G.), University
of Copenhagen BioScaRT Program of Excellence (G. S., I.A.J., D. P. D.
W., G. W. and U. G.), Lundbeck Foundation Center for Biomembranes in
Nanomedicine (U. G. and J.E.), the Lundbeck Foundation (M. R.) the Novo
Nordisk Foundation (U. G.) and Fabrikant Vilhelm Pedersen og Hustrus
Mindelegat (U.G.).
NR 46
TC 18
Z9 18
U1 4
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2013
VL 4
AR 1580
DI 10.1038/ncomms2568
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 143NJ
UT WOS:000318873900034
PM 23481388
ER
PT J
AU Shen, H
Fridley, BL
Song, HL
Lawrenson, K
Cunningham, JM
Ramus, SJ
Cicek, MS
Tyrer, J
Stram, D
Larson, MC
Kobel, M
Ziogas, A
Zheng, W
Yang, HP
Wu, AH
Wozniak, EL
Woo, YL
Winterhoff, B
Wik, E
Whittemore, AS
Wentzensen, N
Weber, RP
Vitonis, AF
Vincent, D
Vierkant, RA
Vergote, I
Van Den Berg, D
Van Altena, AM
Tworoger, SS
Thompson, PJ
Tessier, DC
Terry, KL
Teo, SH
Templeman, C
Stram, DO
Southey, MC
Sieh, W
Siddiqui, N
Shvetsov, YB
Shu, XO
Shridhar, V
Wang-Gohrke, S
Severi, G
Schwaab, I
Salvesen, HB
Rzepecka, IK
Runnebaum, IB
Rossing, MA
Rodriguez-Rodriguez, L
Risch, HA
Renner, SP
Poole, EM
Pike, MC
Phelan, CM
Pelttari, LM
Pejovic, T
Paul, J
Orlow, I
Omar, SZ
Olson, SH
Odunsi, K
Nickels, S
Nevanlinna, H
Ness, RB
Narod, SA
Nakanishi, T
Moysich, KB
Monteiro, ANA
Moes-Sosnowska, J
Modugno, F
Menon, U
McLaughlin, JR
McGuire, V
Matsuo, K
Adenan, NAM
Massuger, LFAG
Lurie, G
Lundvall, L
Lubinski, J
Lissowska, J
Levine, DA
Leminen, A
Lee, AW
Le, ND
Lambrechts, S
Lambrechts, D
Kupryjanczyk, J
Krakstad, C
Konecny, GE
Kjaer, SK
Kiemeney, LA
Kelemen, LE
Keeney, GL
Karlan, BY
Karevan, R
Kalli, KR
Kajiyama, H
Ji, BT
Jensen, A
Jakubowska, A
Iversen, E
Hosono, S
Hogdall, CK
Hogdall, E
Hoatlin, M
Hillemanns, P
Heitz, F
Hein, R
Harter, P
Halle, MK
Hall, P
Gronwald, J
Gore, M
Goodman, MT
Giles, GG
Gentry-Maharaj, A
Garcia-Closas, M
Flanagan, JM
Fasching, PA
Ekici, AB
Edwards, R
Eccles, D
Easton, DF
Durst, M
du Bois, A
Dork, T
Doherty, JA
Despierre, E
Dansonka-Mieszkowska, A
Cybulski, C
Cramer, DW
Cook, LS
Chen, XQ
Charbonneau, B
Chang-Claude, J
Campbell, I
Butzow, R
Bunker, CH
Brueggmann, D
Brown, R
Brooks-Wilson, A
Brinton, LA
Bogdanova, N
Block, MS
Benjamin, E
Beesley, J
Beckmann, MW
Bandera, EV
Baglietto, L
Bacot, F
Armasu, SM
Antonenkova, N
Anton-Culver, H
Aben, KK
Liang, D
Wu, XF
Lu, KR
Hildebrandt, MAT
Schildkraut, JM
Sellers, TA
Huntsman, D
Berchuck, A
Chenevix-Trench, G
Gayther, SA
Pharoah, PDP
Laird, PW
Goode, EL
Pearce, CL
AF Shen, Hui
Fridley, Brooke L.
Song, Honglin
Lawrenson, Kate
Cunningham, Julie M.
Ramus, Susan J.
Cicek, Mine S.
Tyrer, Jonathan
Stram, Douglas
Larson, Melissa C.
Koebel, Martin
Ziogas, Argyrios
Zheng, Wei
Yang, Hannah P.
Wu, Anna H.
Wozniak, Eva L.
Woo, Yin Ling
Winterhoff, Boris
Wik, Elisabeth
Whittemore, Alice S.
Wentzensen, Nicolas
Weber, Rachel Palmieri
Vitonis, Allison F.
Vincent, Daniel
Vierkant, Robert A.
Vergote, Ignace
Van Den Berg, David
Van Altena, Anne M.
Tworoger, Shelley S.
Thompson, Pamela J.
Tessier, Daniel C.
Terry, Kathryn L.
Teo, Soo-Hwang
Templeman, Claire
Stram, Daniel O.
Southey, Melissa C.
Sieh, Weiva
Siddiqui, Nadeem
Shvetsov, Yurii B.
Shu, Xiao-Ou
Shridhar, Viji
Wang-Gohrke, Shan
Severi, Gianluca
Schwaab, Ira
Salvesen, Helga B.
Rzepecka, Iwona K.
Runnebaum, Ingo B.
Rossing, Mary Anne
Rodriguez-Rodriguez, Lorna
Risch, Harvey A.
Renner, Stefan P.
Poole, Elizabeth M.
Pike, Malcolm C.
Phelan, Catherine M.
Pelttari, Liisa M.
Pejovic, Tanja
Paul, James
Orlow, Irene
Omar, Siti Zawiah
Olson, Sara H.
Odunsi, Kunle
Nickels, Stefan
Nevanlinna, Heli
Ness, Roberta B.
Narod, Steven A.
Nakanishi, Toru
Moysich, Kirsten B.
Monteiro, Alvaro N. A.
Moes-Sosnowska, Joanna
Modugno, Francesmary
Menon, Usha
McLaughlin, John R.
McGuire, Valerie
Matsuo, Keitaro
Adenan, Noor Azmi Mat
Massuger, Leon F. A. G.
Lurie, Galina
Lundvall, Lene
Lubinski, Jan
Lissowska, Jolanta
Levine, Douglas A.
Leminen, Arto
Lee, Alice W.
Le, Nhu D.
Lambrechts, Sandrina
Lambrechts, Diether
Kupryjanczyk, Jolanta
Krakstad, Camilla
Konecny, Gottfried E.
Kjaer, Susanne Krueger
Kiemeney, Lambertus A.
Kelemen, Linda E.
Keeney, Gary L.
Karlan, Beth Y.
Karevan, Rod
Kalli, Kimberly R.
Kajiyama, Hiroaki
Ji, Bu-Tian
Jensen, Allan
Jakubowska, Anna
Iversen, Edwin
Hosono, Satoyo
Hogdall, Claus K.
Hogdall, Estrid
Hoatlin, Maureen
Hillemanns, Peter
Heitz, Florian
Hein, Rebecca
Harter, Philipp
Halle, Mari K.
Hall, Per
Gronwald, Jacek
Gore, Martin
Goodman, Marc T.
Giles, Graham G.
Gentry-Maharaj, Aleksandra
Garcia-Closas, Montserrat
Flanagan, James M.
Fasching, Peter A.
Ekici, Arif B.
Edwards, Robert
Eccles, Diana
Easton, Douglas F.
Duerst, Matthias
du Bois, Andreas
Doerk, Thilo
Doherty, Jennifer A.
Despierre, Evelyn
Dansonka-Mieszkowska, Agnieszka
Cybulski, Cezary
Cramer, Daniel W.
Cook, Linda S.
Chen, Xiaoqing
Charbonneau, Bridget
Chang-Claude, Jenny
Campbell, Ian
Butzow, Ralf
Bunker, Clareann H.
Brueggmann, Doerthe
Brown, Robert
Brooks-Wilson, Angela
Brinton, Louise A.
Bogdanova, Natalia
Block, Matthew S.
Benjamin, Elizabeth
Beesley, Jonathan
Beckmann, Matthias W.
Bandera, Elisa V.
Baglietto, Laura
Bacot, Francois
Armasu, Sebastian M.
Antonenkova, Natalia
Anton-Culver, Hoda
Aben, Katja K.
Liang, Dong
Wu, Xifeng
Lu, Karen
Hildebrandt, Michelle A. T.
Schildkraut, Joellen M.
Sellers, Thomas A.
Huntsman, David
Berchuck, Andrew
Chenevix-Trench, Georgia
Gayther, Simon A.
Pharoah, Paul D. P.
Laird, Peter W.
Goode, Ellen L.
Pearce, Celeste Leigh
CA PRACTICAL Consortium
Australian Ovarian Canc Study Grp
Australian Canc Study
TI Epigenetic analysis leads to identification of HNF1B as a
subtype-specific susceptibility gene for ovarian cancer
SO NATURE COMMUNICATIONS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CLEAR-CELL CARCINOMA; PROSTATE-CANCER; COMMON
VARIANTS; RISK; LOCI; MODY
AB HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR) = 1.13, P = 3.1 x 10(-10)) and clear cell (rs11651755 OR = 0.77, P = 1.6 x 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes.
C1 [Shen, Hui; Laird, Peter W.] Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, USC Epigenome Ctr, Los Angeles, CA 90033 USA.
[Fridley, Brooke L.] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66160 USA.
[Song, Honglin; Tyrer, Jonathan; Easton, Douglas F.; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Cambridge CB1 8RN, England.
[Lawrenson, Kate; Ramus, Susan J.; Stram, Douglas; Wu, Anna H.; Van Den Berg, David; Stram, Daniel O.; Pike, Malcolm C.; Lee, Alice W.; Karevan, Rod; Gayther, Simon A.; Pearce, Celeste Leigh] Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Cunningham, Julie M.; Shridhar, Viji] Mayo Clin, Dept Lab Med & Pathol, Div Expt Pathol, Rochester, MN 55905 USA.
[Cicek, Mine S.; Goode, Ellen L.] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN 55905 USA.
[Larson, Melissa C.; Vierkant, Robert A.; Armasu, Sebastian M.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
[Koebel, Martin] Univ Calgary, Calgary Lab Serv, Dept Pathol & Lab Med, Calgary, AB T2N 2T9, Canada.
[Ziogas, Argyrios; Shu, Xiao-Ou; Anton-Culver, Hoda] Univ Calif Irvine, Sch Med, Ctr Canc Genet Res & Prevent, Dept Epidemiol, Irvine, CA 92697 USA.
[Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr, Nashville, TN 37232 USA.
[Yang, Hannah P.; Wentzensen, Nicolas; Brinton, Louise A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Wozniak, Eva L.; Menon, Usha; Gentry-Maharaj, Aleksandra] UCL EGA Inst Womens Hlth, Gynaecol Canc Res Ctr, London NW1 2BU, England.
[Woo, Yin Ling; Omar, Siti Zawiah; Adenan, Noor Azmi Mat] Univ Malaya, UM Canc Res Inst, Fac Med, Dept Obstet & Gynaecol, Kuala Lumpur 59100, Malaysia.
[Winterhoff, Boris] Mayo Clin, Dept Obstet & Gynecol, Rochester, MN 55905 USA.
[Wik, Elisabeth; Salvesen, Helga B.; Krakstad, Camilla; Halle, Mari K.] Haukeland Hosp, Dept Gynecol & Obstet, N-5006 Bergen, Norway.
[Wik, Elisabeth; Salvesen, Helga B.; Krakstad, Camilla; Halle, Mari K.] Univ Bergen, Dept Clin Sci, N-5006 Bergen, Norway.
[Whittemore, Alice S.; Sieh, Weiva; McGuire, Valerie] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Whittemore, Alice S.; Sieh, Weiva; McGuire, Valerie] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27708 USA.
[Vitonis, Allison F.; Terry, Kathryn L.; Cramer, Daniel W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA.
[Vincent, Daniel; Tessier, Daniel C.; Bacot, Francois] Genome Quebec, Montreal, PQ H3A 0G1, Canada.
[Vergote, Ignace; Lambrechts, Sandrina; Lambrechts, Diether; Despierre, Evelyn] VIB, Vesalius Res Ctr, B-3000 Louvain, Belgium.
[Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn] Univ Hosp Leuven, Dept Obstet & Gynaecol, Div Gynecol Oncol, B-3000 Louvain, Belgium.
[Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn] Univ Hosp Leuven, Leuven Canc Inst, B-3000 Louvain, Belgium.
[Van Altena, Anne M.; Massuger, Leon F. A. G.] Radboud Univ Nijmegen, Med Ctr, Dept Gynaecol, NL-6500 HB Nijmegen, Netherlands.
[Tworoger, Shelley S.; Poole, Elizabeth M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Tworoger, Shelley S.; Terry, Kathryn L.; Poole, Elizabeth M.; Cramer, Daniel W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Thompson, Pamela J.; Shvetsov, Yurii B.; Lurie, Galina] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96813 USA.
[Teo, Soo-Hwang] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya 47500, Malaysia.
[Teo, Soo-Hwang] Univ Malaya, Med Ctr, Canc Res Inst, Kuala Lumpur 59100, Malaysia.
[Templeman, Claire; Brueggmann, Doerthe] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic 3053, Australia.
[Siddiqui, Nadeem] Glasgow Royal Infirm, Dept Gynaecol Oncol, Glasgow G4 0SF, Lanark, Scotland.
[Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, D-89091 Ulm, Germany.
[Severi, Gianluca; Giles, Graham G.; Baglietto, Laura] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3053, Australia.
[Severi, Gianluca; Giles, Graham G.; Baglietto, Laura] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia.
[Schwaab, Ira] Inst Human Genet Wiesbaden, D-65187 Wiesbaden, Germany.
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[Runnebaum, Ingo B.; Duerst, Matthias] Jena Univ Hosp, Dept Gynecol & Obstet, D-07743 Jena, Germany.
[Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98109 USA.
[Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98109 USA.
[Rodriguez-Rodriguez, Lorna; Bandera, Elisa V.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ 08901 USA.
[Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT 06520 USA.
[Renner, Stefan P.; Fasching, Peter A.; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Ctr Comprehens Canc, Dept Gynecol & Obstet, D-91054 Erlangen, Germany.
[Pike, Malcolm C.; Orlow, Irene; Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
[Phelan, Catherine M.; Monteiro, Alvaro N. A.; Sellers, Thomas A.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Div Populat Sci, Tampa, FL 33612 USA.
[Pelttari, Liisa M.; Nevanlinna, Heli; Leminen, Arto; Butzow, Ralf] Univ Helsinki, Dept Obstet & Gynecol, Helsinki 00029, Hus, Finland.
[Pelttari, Liisa M.; Nevanlinna, Heli; Leminen, Arto; Butzow, Ralf] Univ Helsinki, Cent Hosp, Helsinki 00029, Hus, Finland.
[Pejovic, Tanja] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97239 USA.
[Pejovic, Tanja] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA.
[Paul, James] Beatson West Scotland Canc Ctr, Glasgow G12 0YN, Lanark, Scotland.
[Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA.
[Nickels, Stefan; Hein, Rebecca; Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
[Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77030 USA.
[Narod, Steven A.] Univ Toronto, Womens Coll Res Inst, Toronto, ON M5G IN8, Canada.
[Nakanishi, Toru] Aichi Canc Ctr Cent Hosp, Dept Gynecol Oncol, Nagoya, Aichi 4648681, Japan.
[Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Modugno, Francesmary] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA.
[Modugno, Francesmary; Bunker, Clareann H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Magee Womens Res Inst, Womens Canc Res Program, Pittsburgh, PA 15213 USA.
[McLaughlin, John R.] Univ Toronto, Fac Med, Dalla Lana Sch Publ Hlth, Toronto, ON M5T 3M7, Canada.
[McLaughlin, John R.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G IX5, Canada.
[Matsuo, Keitaro; Hosono, Satoyo] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 4648681, Japan.
[Lundvall, Lene; Kjaer, Susanne Krueger; Hogdall, Claus K.] Copenhagen Univ Hosp, Juliane Marie Ctr, Gynecol Clin, DK-2100 Copenhagen, Denmark.
[Lubinski, Jan; Jakubowska, Anna; Gronwald, Jacek; Cybulski, Cezary] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, PL-70115 Szczecin, Poland.
[Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland.
[Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA.
[Le, Nhu D.] BC Canc Agcy, Vancouver, BC G12 0YN, Canada.
[Lambrechts, Sandrina; Lambrechts, Diether; Despierre, Evelyn] Univ Leuven, Dept Oncol, Lab Translat Genet, B-3000 Louvain, Belgium.
[Konecny, Gottfried E.; Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Kjaer, Susanne Krueger; Jensen, Allan; Hogdall, Estrid] Danish Canc Soc, Res Ctr, DK-2100 Copenhagen, Denmark.
[Kiemeney, Lambertus A.; Aben, Katja K.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & HTA, NL-6500 HB Nijmegen, Netherlands.
[Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6500 HB Nijmegen, Netherlands.
[Kiemeney, Lambertus A.; Aben, Katja K.] Ctr Comprehens Canc, NL-1066 CX Utrecht, Netherlands.
[Kelemen, Linda E.] Alberta Hlth Serv Canc Care, Dept Populat Hlth Res, Calgary, AB T2N 2T9, Canada.
[Kelemen, Linda E.] Univ Calgary, Dept Med Genet & Oncol, Calgary, AB T2N 2T9, Canada.
[Keeney, Gary L.] Mayo Clin, Dept Lab Med & Pathol, Div Anat Pathol, Rochester, MN 55905 USA.
[Karlan, Beth Y.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
[Kalli, Kimberly R.; Block, Matthew S.] Mayo Clin, Dept Med Oncol, Rochester, MN 55905 USA.
[Kajiyama, Hiroaki] Nagoya Univ, Grad Sch Med, Dept Obstet & Gynecol, Nagoya, Aichi 4648601, Japan.
[Ji, Bu-Tian] NCI, Div Canc Etiol & Genet, Bethesda, MD 20892 USA.
[Iversen, Edwin] Duke Univ, Dept Stat Sci, Durham, NC 27708 USA.
[Hogdall, Estrid] Univ Copenhagen, Mol Unit, Dept Pathol, Herlev Hosp, DK-2730 Copenhagen, Denmark.
[Hoatlin, Maureen] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA.
[Hillemanns, Peter] Hannover Med Sch, Clin Obstet, D-30625 Hannover, Germany.
[Hillemanns, Peter] Hannover Med Sch, Clin Gynaecol, D-30625 Hannover, Germany.
[Heitz, Florian; Harter, Philipp; du Bois, Andreas] Kliniken Essen Mitte, Dept Gynecol & Gynecol Oncol, D-45136 Essen, Germany.
[Heitz, Florian; Harter, Philipp; du Bois, Andreas] Dr Horst Schmidt Klin, Dept Gynecol & Gynecol Oncol, D-65199 Wiesbaden, Germany.
[Hein, Rebecca] Univ Cologne, Dept Child & Adolescent Psychiat & Psychotherapy, PMV Res Grp, D-50931 Cologne, Germany.
[Hall, Per] Karolinska Inst, Dept Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Gore, Martin] Royal Marsden Hosp, Gynecol Oncol Unit, London SW3 6JJ, England.
[Goodman, Marc T.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Ctr Inst, Los Angeles, CA 90048 USA.
[Giles, Graham G.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3806, Australia.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Breakthrough Breast Canc Res Ctr, London SW7 3RP, England.
[Flanagan, James M.; Brown, Robert] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London SW7 2AZ, England.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, D-91054 Erlangen, Germany.
[Edwards, Robert] Magee Womens Hosp, Pittsburgh, PA 15213 USA.
[Eccles, Diana] Univ Southampton, Southampton Univ Hosp, Fac Med, Southampton S017 1BJ, Hants, England.
[Doerk, Thilo; Bogdanova, Natalia] Hannover Med Sch, Gynaecol Res Unit, D-30625 Hannover, Germany.
[Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Epidemiol & Biostat Sect, Lebanon, NH 03755 USA.
[Cook, Linda S.; Charbonneau, Bridget] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA.
[Chen, Xiaoqing; Beesley, Jonathan; Chenevix-Trench, Georgia; Australian Canc Study] Queensland Inst Med Res, Dept Genet, Herston, Qld 4006, Australia.
[Campbell, Ian] Peter MacCallum Canc Inst, Div Res, Canc Genet Lab, Melbourne, Vic 3002, Australia.
[Butzow, Ralf] Univ Melbourne, Dept Pathol, Melbourne, Vic 3053, Australia.
[Campbell, Ian] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic 3002, Australia.
[Butzow, Ralf] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki 00029, Hus, Finland.
[Brooks-Wilson, Angela] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC V52 1L3, Canada.
[Benjamin, Elizabeth] UCL, Inst Canc, Dept Pathol, London WC1E 6JJ, England.
[Antonenkova, Natalia] Belarusian Inst Oncol & Med Radiol Aleksandrov NN, Minsk 223040, Byelarus.
[Liang, Dong] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77044 USA.
[Wu, Xifeng; Hildebrandt, Michelle A. T.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Lu, Karen] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
[Schildkraut, Joellen M.] Duke Canc Inst, Canc Prevent Detect & Control Res Program, Durham, NC 27708 USA.
[Huntsman, David] Vancouver Gen Hosp, BC Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada.
[Berchuck, Andrew] Duke Canc Inst, Gynecol Canc Program, Durham, NC 27708 USA.
[Pharoah, Paul D. P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
RP Goode, EL (reprint author), Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN 55905 USA.
EM egoode@mayo.edu
RI campbell, Ian/F-6006-2011; Fridley, Brooke/D-8315-2015; Garcia-Closas,
Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Woo, Yin
Ling/B-5198-2010; Nicklin, James/F-8035-2013; van Altena,
Anne/B-9824-2016; Aben, Katja/G-9686-2016; Bowtell, David/H-1007-2016;
Gronwald, Jacek/A-4576-2017; Brenner, Hermann/B-4627-2017; salvesen,
Helga/C-1187-2017; Wyld, David/B-8893-2015; friedlander,
michael/G-3490-2013; Kiemeney, Lambertus/D-3357-2009; Tang,
Macy/B-9798-2014; Batra, Jyotsna/B-4130-2011; Renner,
Stefan/F-1158-2014; Dork, Thilo/J-8620-2012; Whittemore,
Alice/F-9925-2014; Brooks-Wilson, Angela/E-9399-2012; Teo,
Soo-hwang/H-2353-2014; Bandera, Elisa/M-4169-2014; Laird,
Peter/G-8683-2012; Massuger, Leon/H-8072-2014; Jakubowska,
Anna/O-8050-2014
OI Krakstad, Camilla/0000-0002-0174-8139; Giles,
Graham/0000-0003-4946-9099; Matsuo, Keitaro/0000-0003-1761-6314; Eeles,
Rosalind/0000-0002-3698-6241; Tworoger, Shelley/0000-0002-6986-7046;
Kjaer, Susanne/0000-0002-8347-1398; Monteiro,
Alvaro/0000-0002-8448-4801; Ramus, Susan/0000-0003-0005-7798; Lissowska,
Jolanta/0000-0003-2695-5799; Kobel, Martin/0000-0002-6615-2037;
Nevanlinna, Heli/0000-0002-0916-2976; Halle, Mari/0000-0002-2660-8271;
Orlow, Irene/0000-0001-6234-6961; Fridley, Brooke/0000-0001-7739-7956;
Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
Louise/0000-0003-3853-8562; Woo, Yin Ling/0000-0003-1742-1066; Nicklin,
James/0000-0001-5378-496X; Aben, Katja/0000-0002-0214-2147; Bowtell,
David/0000-0001-9089-7525; Gronwald, Jacek/0000-0002-3643-2871; Brenner,
Hermann/0000-0002-6129-1572; salvesen, Helga/0000-0002-4438-8831; Wyld,
David/0000-0001-9523-4333; friedlander, michael/0000-0002-6488-0604;
Kiemeney, Lambertus/0000-0002-2368-1326; Renner,
Stefan/0000-0003-2057-1268; Brooks-Wilson, Angela/0000-0003-1009-6408;
Bandera, Elisa/0000-0002-8789-2755;
FU European Commission [223175-HEALTH-F2-2009-223175]; Ovarian Cancer
Research Fund; Genetic Associations and Mechanisms in Oncology (GAME-ON)
Network: a NCI Cancer Post-GWAS Initiative [U19-CA148112]; Wellcome
Trust [076113]; Deutsche Krebshilfe; American Cancer Society Early
Detection Professorship [SIOP-06-258-01-COUN]; Canadian Institutes of
Health Research [MSH-87734]; National Institutes of Health
[T32GM067587]; American Cancer Society [CRTG-00-196-01-CCE]; California
Cancer Research Program [00-01389V-20170, N01-CN25403, 2II0200];
Canadian Institutes for Health Research [MOP-86727]; Cancer Council
Victoria; Cancer Council Queensland; Cancer Council New South Wales;
Cancer Council South Australia; Cancer Council Tasmania; Cancer
Foundation of Western Australia; Cancer Institute of New Jersey; Cancer
Research UK [C490/A6187, C490/A10119, C490/A10124, C536/A13086,
C536/A6689]; Celma Mastry Ovarian Cancer Foundation; Danish Cancer
Society [94-222-52]; Norwegian Cancer Society, Helse Vest; Norwegian
Research Council; University of Erlangen-Nuremberg; Eve Appeal; Helsinki
University Central Hospital Research Fund; Imperial Experimental Cancer
Research Centre [C1312/A15589]; Ovarian Cancer Research Fund
[PPD/USC.06]; Nationaal Kankerplan of Belgium; Ministry of Health Labour
and Welfare of Japan; L & S Milken Foundation; Polish Ministry of
Science and Higher Education [4 PO5C 028 14, 2 PO5A 068 27]; Roswell
Park Cancer Institute Alliance Foundation; US National Cancer Institute
[K07-CA095666, K07-CA143047, K07-CA80668, K22-CA138563, N01-CN55424,
N01-PC067001, N01-PC035137, P01-CA017054, P01-CA087696, P50-CA105009,
P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449];
US Army Medical Research and Material Command [DAMD17-98-1-8659,
DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-10-1-0280];
National Health and Medical Research Council of Australia [199600,
400281]; German Federal Ministry of Education and Research of Germany
Programme of Clinical Biomedical Research [01 GB 9401]; state of
Baden-Wurttemberg through Medical Faculty of the University of Ulm
[P.685]; Minnesota Ovarian Cancer Alliance; Mayo Foundation; Fred C. and
Katherine B. Andersen Foundation; Phi Beta Psi Sorority; Lon V. Smith
Foundation [LVS-39420]; Oak Foundation; OHSU Foundation; Mermaid I
project; Rudolf-Bartling Foundation; UK National Institute for Health
Research Biomedical Research Centres at the University of Cambridge;
Imperial College London; University College Hospital 'Womens Health
Theme'; Royal Marsden Hospital; WorkSafeBC; U.S. Natl Canc Inst
[R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, R01-CA061107,
R01-CA061132, R01-CA063682, R01-CA064277, R01-CA067262, R01-CA071766,
R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA087538,
R01-CA092044, R01-095023, R01-CA106414, R01-CA122443]; US Natl Canc Inst
[R01-CA112523, R01-CA114343, R01-CA126841, R01-CA149429, R01-CA141154,
R03-CA113148, R03-CA115195, R37-CA070867, R37-CA70867, U01-CA069417,
U01-CA071966, P30-CA15083, R01CA83918, U24 CA143882]
FX We thank all the individuals who took part in this study and all the
researchers, clinicians and administrative staff who have made possible
the many studies contributing to this work. In particular, we thank: D.
Bowtell, P. M. Webb, A. deFazio, D. Gertig, A. Green, P. Parsons, N.
Hayward and D. Whiteman (AUS); G. Peuteman, T. Van Brussel and D. Smeets
(BEL); the staff of the genotyping unit, S LaBoissie` re and F Robidoux
(Genome Quebec); U. Eilber and T. Koehler (GER); L. Gacucova (HMO); P.
Schurmann, F. Kramer, W. Zheng, T.-W. Park-Simon, K. Beer-Grondke and D.
Schmidt (HJO); S. Windebank, C. Hilker and J. Vollenweider (MAY); the
state cancer registries of AL, AZ, AR, CA, CO, CT, DE, FL, GA, HI, ID,
IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR,
PA, RI, SC, TN, TX, VA, WA and WY (NHS); L. Paddock, M. King, U.
Chandran, A. Samoila and Y. Bensman (NJO); M. Sherman, A. Hutchinson, N.
Szeszenia-Dabrowska, B. Peplonska, W. Zatonski, A. Soni, P. Chao and M.
Stagner (POL); C. Luccarini, P. Harrington, the SEARCH team and ECRIC
(SEA); the Scottish Gynaecological Clinical Trials group and SCOTROC1
investigators (SRO); W.-H. Chow and Y.-T. Gao (SWH); I. Jacobs, M.
Widschwendter, N. Balogun, A. Ryan and J. Ford (UKO); and Carole Pye
(UKR). The Collaborative Oncological Gene-Environment Study (COGS)
project is funded through a European Commission's Seventh Framework
Programme grant (agreement number 223175-HEALTH-F2-2009-223175). The
Ovarian Cancer Association Consortium (OCAC) is supported by a grant
from the Ovarian Cancer Research Fund, thanks to donations by the family
and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific
development and funding of this project were (in part) supported by the
Genetic Associations and Mechanisms in Oncology (GAME-ON) Network: a NCI
Cancer Post-GWAS Initiative (U19-CA148112). This study made use of data
generated by the Wellcome Trust Case Control consortium.; A full list of
the investigators who contributed to the generation of the data is
available from http://www.wtccc.org.uk/. Funding for the project was
provided by the Wellcome Trust under award 076113. The results published
here are in part based upon data generated by The Cancer Genome Atlas
Pilot Project established by the National Cancer Institute and National
Human Genome Research Institute. Information about TCGA, and the
investigators and institutions who constitute the TCGA research network,
can be found at http://cancergenome.nih.gov/. G. C. T. is a Senior
Principal Research Fellow of the National Health and Medical Research
Council, Australia. D. F. E. is a Principal Research Fellow of Cancer
Research UK. P. A. F. is supported by the Deutsche Krebshilfe. B. K.
holds an American Cancer Society Early Detection Professorship
(SIOP-06-258-01-COUN). L. E. K. is supported by a Canadian Institutes of
Health Research Investigator award (MSH-87734). H. S. 1 is supported by
a National Institutes of Health training grant (T32GM067587), 'Training
in Cellular, Biochemical and Molecular Sciences'. Funding of the
constituent studies was provided by the American Cancer Society
(CRTG-00-196-01-CCE); the California Cancer Research Program
(00-01389V-20170, N01-CN25403, 2II0200); the Canadian Institutes for
Health Research (MOP-86727); Cancer Council Victoria; Cancer Council
Queensland; Cancer Council New South Wales; Cancer Council South
Australia; Cancer Council Tasmania; Cancer Foundation of Western
Australia; the Cancer Institute of New Jersey; Cancer Research UK
(C490/A6187, C490/A10119, C490/A10124, C536/A13086 and C536/A6689); the
Celma Mastry Ovarian Cancer Foundation; the Danish Cancer Society
(94-222-52); the Norwegian Cancer Society, Helse Vest, the Norwegian
Research Council, ELAN Funds of the University of Erlangen-Nuremberg;
the Eve Appeal; the Helsinki University Central Hospital Research Fund;
Imperial Experimental Cancer Research Centre (C1312/A15589); the Ovarian
Cancer Research Fund (PPD/USC.06); Nationaal Kankerplan of Belgium;
Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for
Cancer Control from the Ministry of Health Labour and Welfare of Japan;
the L & S Milken Foundation; the Polish Ministry of Science and Higher
Education (4 PO5C 028 14, 2 PO5A 068 27); the Roswell Park Cancer
Institute Alliance Foundation; the US National Cancer Institute
(K07-CA095666, K07-CA143047, K07-CA80668, K22-CA138563, N01-CN55424,
N01-PC067001, N01-PC035137, P01-CA017054, P01-CA087696, P50-CA105009,
P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449,
R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, R01-CA061107,
R01-CA061132, R01-CA063682, R01-CA064277, R01-CA067262, R01-CA071766,
R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA087538,
R01-CA092044, R01-095023, R01-CA106414, R01-CA122443, R01-CA112523,
R01-CA114343, R01-CA126841, R01-CA149429, R01-CA141154, R03-CA113148,
R03-CA115195, R37-CA070867, R37-CA70867, U01-CA069417, U01-CA071966,
P30-CA15083, R01CA83918, U24 CA143882 and Intramural research funds);
the US Army Medical Research and Material Command (DAMD17-98-1-8659,
DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669 and
W81XWH-10-1-0280); the National Health and Medical Research Council of
Australia (199600 and 400281); the German Federal Ministry of Education
and Research of Germany Programme of Clinical Biomedical Research (01 GB
9401); the state of Baden-Wurttemberg through Medical Faculty of the
University of Ulm (P.; 685); the Minnesota Ovarian Cancer Alliance; the
Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the
Phi Beta Psi Sorority; the Lon V. Smith Foundation (LVS-39420); the Oak
Foundation; the OHSU Foundation; the Mermaid I project; the
Rudolf-Bartling Foundation; the UK National Institute for Health
Research Biomedical Research Centres at the University of Cambridge,
Imperial College London, University College Hospital 'Womens Health
Theme' and the Royal Marsden Hospital; and WorkSafeBC. We acknowledge
the contributions of Kyriaki Michailidou, Ali Amin Al Olama and Karoline
Kuchenbaecker to the iCOGS statistical analyses and Shahana Ahmed,
Melanie J. Maranian and Catherine S Healey for their contributions to
the iCOGS genotyping quality-control process. US National Health
Institute/National Center for Research Resources/General Clinical
Research Center M01-RR000056.
NR 33
TC 66
Z9 66
U1 2
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2013
VL 4
AR 1628
DI 10.1038/ncomms2629
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 143NJ
UT WOS:000318873900081
PM 23535649
ER
PT J
AU Valapala, M
Hose, S
Gongora, C
Dong, LJ
Wawrousek, EF
Zigler, JS
Sinha, D
AF Valapala, Mallika
Hose, Stacey
Gongora, Celine
Dong, Lijin
Wawrousek, Eric F.
Zigler, J. Samuel, Jr.
Sinha, Debasish
TI Impaired endolysosomal function disrupts Notch signalling in optic nerve
astrocytes
SO NATURE COMMUNICATIONS
LA English
DT Article
ID LYSOSOMAL ACIDIFICATION; SPONTANEOUS MUTATION; GAMMA-SECRETASE; MOUSE
RETINA; CELL-DEATH; ACTIVATION; ENDOCYTOSIS; BETA-A3/A1-CRYSTALLIN;
DROSOPHILA; RECEPTOR
AB Astrocytes migrate from the optic nerve into the inner retina, forming a template upon which retinal vessels develop. In the Nuc1 rat, mutation in the gene encoding beta A3/A1-crystallin disrupts both Notch signalling in astrocytes and formation of the astrocyte template. Here we show that loss of beta A3/A1-crystallin in astrocytes does not impede Notch ligand binding or extracellular cleavages. However, it affects vacuolar-type proton ATPase (V-ATPase) activity, thereby compromising acidification of the endolysosomal compartments, leading to reduced gamma-secretase-mediated processing and release of the Notch intracellular domain (NICD). Lysosomal-mediated degradation of Notch is also impaired. These defects decrease the level of NICD in the nucleus, inhibiting the expression of Notch target genes. Overexpression of beta A3/A1-crystallin in those same astrocytes restored V-ATPase activity and normal endolysosomal acidification, thereby increasing the levels of gamma-secretase to facilitate optimal Notch signalling. We postulate that beta A3/A1-crystallin is essential for normal endolysosomal acidification, and thereby, normal activation of Notch signalling in astrocytes.
C1 [Valapala, Mallika; Hose, Stacey; Zigler, J. Samuel, Jr.; Sinha, Debasish] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
[Gongora, Celine] INSERM, IRCM, U896, F-34298 Montpellier, France.
[Dong, Lijin; Wawrousek, Eric F.] NEI, NIH, Bethesda, MD 20892 USA.
RP Sinha, D (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
EM Debasish@jhmi.edu
FU National Institutes of Health [EY018636, EY019037, EY01765]; Research to
Prevent Blindness
FX This work was supported by grants from the National Institutes of
Health, EY018636 (D. S.), EY019037 (D. S.) and EY01765 (Wilmer Imaging
Core) and Research to Prevent Blindness (an unrestricted grant to The
Wilmer Eye Institute). D. S. is a recipient of the Sybil B. Harrington
Special Scholar award for Macular Degeneration from Research to Prevent
Blindness. We thank Drs Akrit Sodhi and Xiaoban Xin for providing the
adenoviral vectors and Dr Raphael Kopan for N delta E plasmids. We also
thank Morton F Goldberg, Bidyut Ghosh and Seth Greenbaum for critically
reading the manuscript.
NR 60
TC 18
Z9 18
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2013
VL 4
AR 1629
DI 10.1038/ncomms2624
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 143NJ
UT WOS:000318873900082
PM 23535650
ER
PT J
AU Wu, SD
Zhu, WH
Nhan, T
Toth, JI
Petroski, MD
Wolf, DA
AF Wu, Shuangding
Zhu, Wenhong
Tina Nhan
Toth, Julia I.
Petroski, Matthew D.
Wolf, Dieter A.
TI CAND1 controls in vivo dynamics of the cullin 1-RING ubiquitin ligase
repertoire
SO NATURE COMMUNICATIONS
LA English
DT Article
ID F-BOX PROTEIN; COP9 SIGNALOSOME; SUBSTRATE-ADAPTERS; NEDDYLATION; NEDD8;
CUL1; SCF; ACTIVATION; TIP120A; CONJUGATION
AB The combinatorial architecture of cullin 1-RING ubiquitin ligases, in which multiple F-box containing substrate receptors compete for access to CUL1, poses special challenges to assembling cullin 1-RING ubiquitin ligase complexes through high affinity protein interactions while maintaining the flexibility to dynamically sample the entire F-box containing substrate receptor repertoire. Here, using highly quantitative mass spectrometry, we demonstrate that this problem is addressed by CAND1, a factor that controls the dynamics of the global cullin 1-RING ubiquitin ligase network by promoting the assembly of newly synthesized F-box containing substrate receptors with CUL1-RBX1 core complexes. Our studies of in vivo cullin 1-RING ubiquitin ligase dynamics and in vitro biochemical findings showing that CAND1 can displace F-box containing substrate receptors from Cul1p suggest that CAND1 functions in a cycle that serves to exchange F-box containing substrate receptors on CUL1 cores. We propose that this cycle assures comprehensive sampling of the entire F-box containing substrate receptor repertoire in order to maintain the cullin 1-RING ubiquitin ligase landscape, a function that we show to be critical for substrate degradation and normal physiology.
C1 [Wu, Shuangding; Tina Nhan; Toth, Julia I.; Petroski, Matthew D.; Wolf, Dieter A.] Sanford Burnham Med Res Inst, Signal Transduct Program, La Jolla, CA 92037 USA.
[Zhu, Wenhong; Wolf, Dieter A.] Sanford Burnham Med Res Inst, NCI, Canc Ctr Prote Facil, La Jolla, CA 92037 USA.
[Wolf, Dieter A.] Sanford Burnham Med Res Inst, San Diego Ctr Syst Biol, La Jolla, CA 92037 USA.
RP Wolf, DA (reprint author), Sanford Burnham Med Res Inst, Signal Transduct Program, La Jolla, CA 92037 USA.
EM dwolf@sanfordburnham.org
OI Wolf, Dieter/0000-0002-3761-1070
FU NIH [GM59780, P20 CA132386-03, P50 GM085764-03]
FX We thank Y. Takayama for Ams2p antibodies and Z. Ronai for review of the
manuscript. We also thank R. Deshaies and T. Kurz for sharing results
prior to publication. This work was supported by NIH grants GM59780, P20
CA132386-03 and P50 GM085764-03.
NR 39
TC 35
Z9 35
U1 3
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2013
VL 4
AR 1642
DI 10.1038/ncomms2636
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 143NJ
UT WOS:000318873900095
PM 23535663
ER
PT J
AU White, SF
Frick, PJ
Lawing, K
Bauer, D
AF White, Stuart F.
Frick, Paul J.
Lawing, Kathryn
Bauer, Daliah
TI CallousUnemotional Traits and Response to Functional Family Therapy in
Adolescent Offenders
SO BEHAVIORAL SCIENCES & THE LAW
LA English
DT Article
ID CALLOUS-UNEMOTIONAL TRAITS; DISRUPTIVE BEHAVIOR DISORDERS; PSYCHOPATHIC
FEATURES; ANTISOCIAL-BEHAVIOR; CONDUCT PROBLEMS; SEX OFFENDERS;
RECIDIVISM; CHILDREN; METAANALYSIS; VIOLENCE
AB OBJECTIVE The current study examined whether callousunemotional (CU) traits moderated the effectiveness of Functional Family Therapy for juvenile justice involved adolescents. METHOD Participants were all youths (n=134) who had been arrested and participated in an FFT program provided in a community mental health center over a 20-month period (mean age 15.34, 71.6% males, 59% African-American). Parent and self-report ratings of emotional, behavioral, and social functioning, multi-informant ratings of treatment progress, and probation/arrest records were used as outcome indicators. RESULTS CU traits were associated with poorer behavioral, emotional, and social adjustment prior to treatment but they were also associated with greater improvements in adjustment over the course of treatment. CU traits were not associated with significantly lower rates of participation or higher rates of treatment dropout, and the association between CU traits and risk for violent charges decreased after treatment at 6- and 12-month follow-ups. However, CU traits were still correlated with poorer levels of adjustment post-treatment, less perceived change over treatment by youth and their parents, and increased likelihood of violent offending during treatment. CONCLUSIONS The results of this study indicate that FFT can lead to improvements in youth with CU traits; however, they enter treatment with a greater number of symptoms and are at higher risk for committing violence during treatment than other youth. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [White, Stuart F.] NIMH, Bethesda, MD 20892 USA.
[Frick, Paul J.; Lawing, Kathryn] Univ New Orleans, New Orleans, LA 70148 USA.
RP White, SF (reprint author), NIMH, 9000 Rockville Pike,Bldg 15k,Room 300-C, Bethesda, MD 20892 USA.
EM whitesf@mail.nih.gov
NR 43
TC 15
Z9 15
U1 2
U2 38
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0735-3936
J9 BEHAV SCI LAW
JI Behav. Sci. Law
PD MAR-APR
PY 2013
VL 31
IS 2
BP 271
EP 285
DI 10.1002/bsl.2041
PG 15
WC Psychology, Applied; Law
SC Psychology; Government & Law
GA 139ZA
UT WOS:000318622600008
PM 23172768
ER
PT J
AU Morens, DM
Folkers, GK
Fauci, AS
AF Morens, David M.
Folkers, Gregory K.
Fauci, Anthony S.
TI Dengue: The Continual Re-Emergence of a Centuries-Old Disease
SO ECOHEALTH
LA English
DT Editorial Material
C1 [Morens, David M.; Folkers, Gregory K.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Morens, DM (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dmorens@niaid.nih.gov
NR 8
TC 2
Z9 2
U1 1
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1612-9202
J9 ECOHEALTH
JI EcoHealth
PD MAR
PY 2013
VL 10
IS 1
BP 104
EP 106
DI 10.1007/s10393-013-0825-7
PG 3
WC Biodiversity Conservation; Ecology; Environmental Sciences
SC Biodiversity & Conservation; Environmental Sciences & Ecology
GA 143CM
UT WOS:000318843900013
PM 23456289
ER
PT J
AU Yan, S
Li, ZJ
Thiele, CJ
AF Yan, Shuang
Li, Zhijie
Thiele, Carol J.
TI Inhibition of STAT3 with orally active JAK inhibitor, AZD1480, decreases
tumor growth in Neuroblastoma and Pediatric Sarcomas In vitro and In
vivo
SO ONCOTARGET
LA English
DT Article
DE neuroblastoma; Ewing sarcoma; rhabdomyosarcoma; JAK inhibitor; STAT3
ID SIGNAL TRANSDUCER; CONSTITUTIVE ACTIVATION; PROGNOSTIC-FACTORS; EWING
SARCOMA; SOLID TUMORS; CELL-GROWTH; CANCER; RHABDOMYOSARCOMA;
RESISTANCE; TRANSCRIPTION-3
AB The IL-6/JAK/STAT pathway is a key signal transduction pathway implicated in the pathogenesis of many human cancers, suggesting that kinase inhibitors targeting JAK/STAT3 may have a broad spectrum of antitumor activity. AZD1480, a pharmacological JAK1/2 inhibitor, exhibits anti-tumor potency in multiple adult malignancies. To evaluate the efficacy of inhibition of JAK/STAT3 signal transduction pathway we assessed the activity of AZD1480 in pediatric malignancies using preclinical models of three highly malignant pediatric solid tumors: neuroblastoma (NB), rhabdomyosarcoma (RMS) and the Ewing Sarcoma Family Tumors (ESFT). In this study, we employed panels of biomedical and biological experiments to evaluate the in vitro and in vivo activity of AZD1480 in NB, RMS and ESFT. Our data indicate that AZD1480 blocks endogenous as well as IL-6 induced STAT3 activation. AZD1480 decreases cell viability in 7/7NB, 7/7RMS and 2/2 ESFT cell lines (median EC50 is 1.5 mu M, ranging from 0.36-5.37 mu M). AZD1480 induces cell growth inhibition and caspase-dependent apoptosis in vitro and decreases expression of STAT3 target genes, including cell cycle regulators CyclinD1, 3 and CDC25A, anti-apoptotic genes Bcl-2 and survivin, the metastasis-related factor TIMP-1 and c-Myc. In vivo studies showed AZD1480 significantly decreased tumor growth and prolonged overall survival in tumor-bearing mice. Tumors from AZD1480-treated mice showed inhibition of activated STAT3 as well as decreased expression of STAT3 downstream targets. Our study provides strong evidence of the anti-tumor growth potency of JAK inhibitor AZD1480 in pediatric solid tumors, providing proof-of principle that inhibition of the JAK/STAT3 signal transduction could be a promising therapeutic target for high-risk pediatric solid tumors.
C1 [Yan, Shuang; Li, Zhijie; Thiele, Carol J.] NCI, Ctr Canc Res, Pediat Oncol Branch, Cell & Mol Biol Sect, Bethesda, MD 20892 USA.
RP Thiele, CJ (reprint author), NCI, Ctr Canc Res, Pediat Oncol Branch, Cell & Mol Biol Sect, Bethesda, MD 20892 USA.
EM ct47a@nih.gov
RI Yan, Shuang/N-7131-2013
FU NIH, National Cancer Institute; Center for Cancer Research
FX We would like to thank: Dr. Choh Yeung (Pediatric Oncology Branch,
National Cancer Institute) for his kind assistance with the orthotropic
mice models; AstraZeneca (Boston) for provide AZD1480; Dr. Dennis Huszar
(Cancer Bioscience, AstraZeneca) for coordinating the supply of AZD1480
and suggesting on the dose of AZD1480 on animal models; Dr. Stanley He
(Pediatric Oncology Branch, National Cancer Institute) for editing the
manuscript; Dr. Lee Helman (Pediatric Oncology Branch, National Cancer
Institute) for critical review and discussion on the manuscript. All
xenograft studies were approved by the Animal Care and Use Committee of
the National Cancer Institute in accordance with the institutional
guidelines (Protocol Number: PB-023). This research was supported by the
Intramural Research Program of the NIH, National Cancer Institute, and
Center for Cancer Research.
NR 35
TC 30
Z9 34
U1 0
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD MAR
PY 2013
VL 4
IS 3
BP 433
EP 445
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 142FW
UT WOS:000318783400007
PM 23531921
ER
PT J
AU Zhurkin, VB
Olson, WK
AF Zhurkin, Victor B.
Olson, Wilma K.
TI Can nucleosomal DNA be described by an elastic model? Comment on
"Sequence-dependent collective properties of DNAs and their role in
biological systems" by Pasquale De Santis and Anita Scipioni
SO PHYSICS OF LIFE REVIEWS
LA English
DT Editorial Material
ID DEFORMATIONS; MECHANICS; CHROMATIN; HISTONE
C1 [Zhurkin, Victor B.] NCI, NIH, Bethesda, MD 20892 USA.
[Olson, Wilma K.] Rutgers State Univ, Wright Rieman Labs, Piscataway, NJ 08854 USA.
RP Zhurkin, VB (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM zhurkin@nih.gov; wilma.olson@rutgers.edu
FU NIGMS NIH HHS [R01 GM034809]
NR 17
TC 1
Z9 1
U1 3
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1571-0645
J9 PHYS LIFE REV
JI Phys. Life Rev.
PD MAR
PY 2013
VL 10
IS 1
BP 70
EP 72
DI 10.1016/j.plrev.2013.01.009
PG 3
WC Biology; Biophysics
SC Life Sciences & Biomedicine - Other Topics; Biophysics
GA 139MR
UT WOS:000318587300011
PM 23587120
ER
PT J
AU Wilcox, AJ
Bonde, JPE
AF Wilcox, Allen J.
Bonde, Jens Peter E.
TI On environmental threats to male infertility
SO ASIAN JOURNAL OF ANDROLOGY
LA English
DT Editorial Material
ID TESTICULAR DYSGENESIS SYNDROME; IN-UTERO EXPOSURE; SPERM COUNTS; SEMEN
QUALITY; ENDOCRINE DISRUPTION; REPRODUCTIVE-TRACT; FERTILITY; PREGNANCY;
PHTHALATE; SMOKING
C1 [Wilcox, Allen J.] NIEHS, Epidemiol Branch, Durham, NC 27709 USA.
[Bonde, Jens Peter E.] Univ Copenhagen Hosp, Dept Occupat & Environm Med, DK-2400 Copenhagen NV, Denmark.
RP Wilcox, AJ (reprint author), NIEHS, Epidemiol Branch, Durham, NC 27709 USA.
EM wilcox@niehs.nih.gov
OI Wilcox, Allen/0000-0002-3376-1311
FU Intramural NIH HHS
NR 37
TC 6
Z9 9
U1 0
U2 22
PU ACTA PHARMACOLOGICA SINICA
PI SHANGHAI
PA 294 TAI-YUAN RD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1008-682X
J9 ASIAN J ANDROL
JI Asian J. Androl.
PD MAR
PY 2013
VL 15
IS 2
SI SI
BP 199
EP 200
DI 10.1038/aja.2012.153
PG 2
WC Andrology; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 140XV
UT WOS:000318690700011
PM 23334202
ER
PT J
AU Liaudet, L
Rosenblatt-Velin, N
Pacher, P
AF Liaudet, Lucas
Rosenblatt-Velin, Nathalie
Pacher, Pal
TI Role of Peroxynitrite in the Cardiovascular Dysfunction of Septic Shock
SO CURRENT VASCULAR PHARMACOLOGY
LA English
DT Article
DE Septic shock; cardiovascular dysfunction; nitric oxide; superoxide;
peroxynitrite; oxidative stress; nitration; poly(ADP-ribose) polymerase;
animal models
ID PROTEIN-TYROSINE NITRATION; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B;
POLY(ADP-RIBOSE) POLYMERASE ACTIVATION; MANGANESE SUPEROXIDE-DISMUTASE;
SPLANCHNIC ARTERY-OCCLUSION; OXIDATIVE STRESS; HEART-FAILURE; IN-VIVO;
MATRIX METALLOPROTEINASES
AB The intense systemic inflammatory response characterizing septic shock is associated with an increased generation of free radicals by multiple cell types in cardiovascular and non cardiovascular tissues. The oxygen-centered radical superoxide anion (O-2(center dot-)) rapidly reacts with the nitrogen-centered radical nitric oxide (NO center dot) to form the potent oxidant species peroxynitrite. Peroxynitrite oxidizes multiple targets molecules, either directly or via the secondary generation of highly reactive radicals, resulting in significant alterations in lipids, proteins and nucleic acids, with significant cytotoxic consequences. The formation of peroxynitrite is a key pathophysiological mechanism contributing to the cardiovascular collapse of septic shock, promoting vascular contractile failure, endothelial and myocardial dysfunction, and is also implicated in the occurrence of multiple organ dysfunction in this setting. The recent development of various porphyrin-based pharmacological compounds accelerating the degradation of peroxynitrite has allowed to specifically address these pathophysiological roles of peroxynitrite in experimental septic shock. Such agents, including 5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrinato iron III chloride (FeTTPs), manganese tetrakis(4-N-methylpyridyl) porphyrin (MnTMPyP), Fe(III) tetrakis-2-(N-triethylene glycol monomethyl ether) pyridyl porphyrin) (FP-15) and WW-85, have been shown to improve the cardiovascular and multiple organ failure in small and large animal models of septic shock. Therefore, these findings support the development of peroxynitrite decomposition catalysts as potentially useful novel therapeutic agents to restore cardiovascular function in sepsis.
C1 [Liaudet, Lucas] Fac Biol & Med, Dept Intens Care Med, CH-1010 Lausanne, Switzerland.
[Liaudet, Lucas; Rosenblatt-Velin, Nathalie] Fac Biol & Med, Div Clin Pathophysiol, CH-1010 Lausanne, Switzerland.
[Liaudet, Lucas; Rosenblatt-Velin, Nathalie] Fac Biol & Med, Dept Physiol, CH-1010 Lausanne, Switzerland.
Univ Hosp Med Ctr, CH-1011 Lausanne, Switzerland.
[Pacher, Pal] NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD USA.
RP Liaudet, L (reprint author), BH 08 621 Univ Hosp Med, Dept Intens Care Med, CH-1011 Lausanne, Switzerland.
EM lucas.liaudet@chuv.ch
RI Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017
OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930
FU Swiss National Foundation for Scientific Research [Nr 310030_135394/1,
310030_132491]; Intramural Program of National Institutes of
Health/NIAAA
FX Supported by grants from the Swiss National Foundation for Scientific
Research (Nr 310030_135394/1 to LL and 310030_132491 to NRV) and
Intramural Program of National Institutes of Health/NIAAA (to PP).
NR 150
TC 12
Z9 15
U1 1
U2 22
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1570-1611
J9 CURR VASC PHARMACOL
JI Current Vascular Pharmacology
PD MAR
PY 2013
VL 11
IS 2
BP 196
EP 207
PG 12
WC Pharmacology & Pharmacy; Peripheral Vascular Disease
SC Pharmacology & Pharmacy; Cardiovascular System & Cardiology
GA 139RV
UT WOS:000318602600009
PM 23506498
ER
PT J
AU Tsao, CW
O'Donnell, CJ
AF Tsao, Connie W.
O'Donnell, Christopher J.
TI Lipid profiles and coronary artery plaque by CT angiography: Promise for
translation of biology to imaging
SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY
LA English
DT Editorial Material
ID MULTISLICE COMPUTED-TOMOGRAPHY; ACUTE CHEST-PAIN;
CARDIOVASCULAR-DISEASE; MAGNETIC-RESONANCE; PROGNOSTIC VALUE; RISK;
CALCIUM; SUBFRACTIONATION; APOLIPOPROTEINS; CHOLESTEROL
C1 [Tsao, Connie W.] Framingham Heart Dis Epidemiol Study, Natl Heart Lung & Blood Inst, Framingham, MA 01702 USA.
Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA.
Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
RP Tsao, CW (reprint author), Framingham Heart Dis Epidemiol Study, Natl Heart Lung & Blood Inst, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
FU Intramural NIH HHS [ZIA HL006002-06, Z99 HL999999, ZIA HL006002-05]
NR 28
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-5925
J9 J CARDIOVASC COMPUT
JI J. Cardiovasc. Comput. Tomogr.
PD MAR-APR
PY 2013
VL 7
IS 2
BP 91
EP 93
DI 10.1016/j.jcct.2013.02.001
PG 3
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 137WV
UT WOS:000318469800004
PM 23622504
ER
PT J
AU Robledo, R
Lorenz, J
Beck, J
Else, J
Bender, P
AF Robledo, Renato
Lorenz, Joseph
Beck, Jeanne
Else, James
Bender, Patrick
TI Genetic Analysis of Putative Familial Relationships in a Captive
Chimpanzee (Pan troglodytes) Population
SO COLLEGIUM ANTROPOLOGICUM
LA English
DT Article
DE nonhuman primates; microsatellite; genotyping; pedigree; heterozygosity
ID HUMAN GENOME; LINKAGE MAP; MICROSATELLITES; APES
AB Twelve autosomal dinucleotide repeat loci were analyzed in chimpanzees genomes by DNA amplification using primers designed for analysis of human loci. The markers span the entire length of human chromosomes 21 and 22. Nine markers were polymorphic in chimpanzee as well, with a somewhat comparable level of polymorphism and allele size range. Even in the presence of very limited information and in spite of missing samples, it was possible to reconstruct a complex pedigree and to provide molecular data that corroborate family relationships that were deduced from cage history and behavioral data. The conclusions were further supported by mitochondrial DNA analysis. The data presented in this report show that the extremely abundant source of human markers may be exploited to validate, with molecular evidence, hypotheses on individual relationship or alleged pedigrees, based upon behavioral observations.
C1 [Robledo, Renato] Univ Cagliari, Dept Biomed Sci, I-09042 Cagliari, Italy.
[Lorenz, Joseph] Cent Washington Univ, Dept Anthropol & Museum Studies, Ellensburg, WA USA.
[Beck, Jeanne] Coriell Inst Med Res, Camden, NJ USA.
[Else, James] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Bender, Patrick] NIMH, Rockville, MD 20857 USA.
RP Robledo, R (reprint author), Univ Cagliari, Dept Biomed Sci, SS 554 Km 4,500, I-09042 Cagliari, Italy.
EM rrobledo@unica.it
NR 12
TC 0
Z9 0
U1 0
U2 7
PU COLLEGIUM ANTROPOLOGICUM
PI ZAGREB
PA INST ANTHROPOLOGICAL RESEARCH, GAJEVA 32, PO BOX 290, HR-10000 ZAGREB,
CROATIA
SN 0350-6134
J9 COLLEGIUM ANTROPOL
JI Coll. Anthropol.
PD MAR
PY 2013
VL 37
IS 1
BP 245
EP 250
PG 6
WC Anthropology
SC Anthropology
GA 134HI
UT WOS:000318200600038
PM 23697280
ER
PT J
AU Turner, MR
Hardiman, O
Benatar, M
Brooks, BR
Chio, A
de Carvalho, M
Ince, PG
Lin, C
Miller, RG
Mitsumoto, H
Nicholson, G
Ravits, J
Shaw, PJ
Swash, M
Talbot, K
Traynor, BJ
Van den Berg, LH
Veldink, JH
Vucic, S
Kiernan, MC
AF Turner, Martin R.
Hardiman, Orla
Benatar, Michael
Brooks, Benjamin R.
Chio, Adriano
de Carvalho, Mamede
Ince, Paul G.
Lin, Cindy
Miller, Robert G.
Mitsumoto, Hiroshi
Nicholson, Garth
Ravits, John
Shaw, Pamela J.
Swash, Michael
Talbot, Kevin
Traynor, Bryan J.
Van den Berg, Leonard H.
Veldink, Jan H.
Vucic, Steve
Kiernan, Matthew C.
TI Controversies and priorities in amyotrophic lateral sclerosis
SO LANCET NEUROLOGY
LA English
DT Review
ID MOTOR-NEURON DISEASE; GENOME-WIDE ASSOCIATION; PROGRESSIVE
MUSCULAR-ATROPHY; DIAGNOSTIC-CRITERIA; CLINICAL-FEATURES; SPORADIC ALS;
NEURODEGENERATIVE DISEASES; NEUROPHYSIOLOGICAL INDEX; HEXANUCLEOTIDE
REPEAT; PREDICTS SURVIVAL
AB Two decades after the discovery that 20% of familial amyotrophic lateral sclerosis (ALS) cases were linked to mutations in the superoxide dismutase-1 (SOD1) gene, a substantial proportion of the remainder of cases of familial ALS have now been traced to an expansion of the intronic hexanucleotide repeat sequence in C9orf72. This breakthrough provides an opportunity to re-evaluate longstanding concepts regarding the cause and natural history of ALS, coming soon after the pathological unification of ALS with frontotemporal dementia through a shared pathological signature of cytoplasmic inclusions of the ubiquitinated protein TDP-43. However, with profound clinical, prognostic, neuropathological, and now genetic heterogeneity, the concept of ALS as one disease appears increasingly untenable. This background calls for the development of a more sophisticated taxonomy, and an appreciation of ALS as the breakdown of a wider network rather than a discrete vulnerable population of specialised motor neurons. Identification of C9orf72 repeat expansions in patients without a family history of ALS challenges the traditional division between familial and sporadic disease. By contrast, the 90% of apparently sporadic cases and incomplete penetrance of several genes linked to familial cases suggest that at least some forms of ALS arise from the interplay of multiple genes, poorly understood developmental, environmental, and age-related factors, as well as stochastic events.
C1 [Turner, Martin R.; Talbot, Kevin] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England.
[Hardiman, Orla] Univ Dublin Trinity Coll, Acad Neurol Unit, Trinity Biomed Sci Inst, Dublin 2, Ireland.
[Hardiman, Orla] Beaumont Hosp, Natl Neurosci Ctr, Dublin 9, Ireland.
[Benatar, Michael] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
[Brooks, Benjamin R.] Univ N Carolina, Dept Neurol, Sch Med, Charlotte, NC 28223 USA.
[Chio, Adriano] Univ Turin, Dept Neurosci, I-10124 Turin, Italy.
[de Carvalho, Mamede] Univ Lisbon, Translat Physiol & Clin Unit, Inst Mol Med, P-1699 Lisbon, Portugal.
[de Carvalho, Mamede] Univ Lisbon, Fac Med, P-1699 Lisbon, Portugal.
[Ince, Paul G.; Shaw, Pamela J.] Univ Sheffield, Sheffield Inst Translat Neurosci SITraN, Sheffield, S Yorkshire, England.
[Lin, Cindy] Univ New S Wales, Fac Med, Sch Med Sci, Sydney, NSW, Australia.
[Miller, Robert G.] Calif Pacific Med Ctr, San Francisco, CA USA.
[Mitsumoto, Hiroshi] New York Presbyterian Columbia Univ Med Ctr, New York, NY USA.
[Nicholson, Garth] ANZAC Res Inst, Northcott Neurosci Lab, Concord, NSW, Australia.
[Ravits, John] Univ Calif San Diego, San Diego, CA 92103 USA.
[Swash, Michael] Queen Mary Sch Med, London, England.
[Swash, Michael] Royal London Hosp, London E1 1BB, England.
[Swash, Michael] Univ Lisbon, Inst Neurosci, P-1699 Lisbon, Portugal.
[Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, Bethesda, MD 20892 USA.
[Van den Berg, Leonard H.; Veldink, Jan H.] Univ Med Ctr Utrecht, Dept Neurol, Utrecht, Netherlands.
[Vucic, Steve] Univ Sydney, Sydney Med Sch Westmead, Sydney, NSW 2006, Australia.
[Kiernan, Matthew C.] Neurosci Res Australia, Sydney, NSW 2031, Australia.
RP Kiernan, MC (reprint author), Neurosci Res Australia, Sydney, NSW 2031, Australia.
EM M.kiernan@unsw.edu.au
RI Traynor, Bryan/G-5690-2010; Kiernan, Matthew/E-4460-2011;
OI de Carvalho, Mamede/0000-0001-7556-0158; Chio,
Adriano/0000-0001-9579-5341; Turner, Martin/0000-0003-0267-3180
FU MDA; ALSA; FDA; NIH; Carolina ALS Research Fund; NINDS; Biogen Idec;
Cytokinetics; Neuraltus; GlaxoSmithKline; National Health and Medical
Research Council; Medical Research Council; Motor Neuron Disease UK Lady
Edith Wolfson Clinician Scientist Fellowship; Health Seventh Framework
Programme [259867]; ALSA (the ALS Association); HRB (the Health Research
Board) Clinical Scientist Award; Research Motor Neuron; NIH, National
Institute on Aging [Z01-AG000949-02]
FX MB receives research funding from MDA, ALSA, FDA, and NIH and provides
consulting services for Cytokinetics and Asublo. OH has received
honoraria for consulting work for Biogen Idec and Cytokinetics. AC
serves on scientific advisory boards for Cytokinetics and Biogen Idec.
BRB receives research funding from Carolina ALS Research Fund, MDA,
ALSA, NINDS, Biogen Idec, Cytokinetics, Neuraltus, and GlaxoSmithKline.
MRT received payment from Biogen Idec for a consultancy on ALS staging.
RGM provided consulting services for Cytokinetics, Asubio, Biogen, and
Knopp and received research support as principal investigator for
Neuraltus, and was on speakers' bureau for Avanir. MCK, MS, KT, BJT,
LHVdB, JHV, SV, MdC, PGI, CL, HM, GN, JR, and PJS declare that they have
no conflicts of interest.; The Fort Denison consensus meeting was
supported by Neuroscience Research Australia and the University of New
South Wales. MCK receives funding support from the National Health and
Medical Research Council. MRT is supported by the Medical Research
Council & Motor Neuron Disease UK Lady Edith Wolfson Clinician Scientist
Fellowship. OH received funding from the Health Seventh Framework
Programme (FP7/2007-2013) under grant agreement No 259867, ALSA (the ALS
Association), HRB (the Health Research Board) Clinical Scientist Award,
and Research Motor Neuron (previously named Motor Neuron Disease
Research Foundation). BJT is supported in part by the Intramural
Research Programs of the NIH, National Institute on Aging
(Z01-AG000949-02). We are grateful to Olaf Ansorge for his expert advice
on table 1. Helpful discussion with Linda Greensmith and Denise
Figlewicz regarding the SOD1 mouse model of ALS is gratefully
acknowledged.
NR 123
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U2 95
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
J9 LANCET NEUROL
JI Lancet Neurol.
PD MAR
PY 2013
VL 12
IS 3
BP 310
EP 322
PG 13
WC Clinical Neurology
SC Neurosciences & Neurology
GA 138SW
UT WOS:000318531300016
PM 23415570
ER
PT J
AU Litton, P
AF Litton, Paul
TI Physician Participation in Executions, the Morality of Capital
Punishment, and the Practical Implications of Their Relationship
SO JOURNAL OF LAW MEDICINE & ETHICS
LA English
DT Review
ID CLINICAL-RESEARCH; LETHAL INJECTION; FORENSIC PSYCHIATRY; ETHICAL
DILEMMAS; MEDICINE; CARE
AB Evidence that some executed prisoners suffered excruciating pain has reinvigorated the ethical debate about physician participation in executions. In widely publicized litigation, death row inmates argue that participation of anesthesiologists in their execution is constitutionally required to minimize the risk of unnecessary suffering. For many years, commentators supported the ethical ban on physician participation reflected in codes of professional medical organizations. However, a recent wave of scholarship concurs with inmate advocates, urging the law to require or permit physician participation. Both the anti- and pro-physician-participation literature share a common premise: the ethics of physician participation should be analyzed independently from the moral status of capital punishment. This considerable literature implausibly divorces the ethics of physician participation from the moral status of the death penalty. Any ethical position on physician involvement requires some judgment about the moral status of capital punishment. The article examines anti- and pro-participation arguments to show that each one either is unpersuasive without discussion of the death penalty's moral status or implicitly assumes a view on the social worth of the death penalty. The article then articulates the practical implications of its arguments for both lawmakers and professional medical organizations.
C1 [Litton, Paul] Univ Missouri, Sch Law, Columbia, MO 65211 USA.
[Litton, Paul] NIH, Dept Clin Bioeth, Bethesda, MD USA.
RP Litton, P (reprint author), Univ Missouri, Sch Law, Columbia, MO 65211 USA.
FU American Society for Law, Medicine, Ethics; SLU's Center for Health Law
Studies
FX An abstract for this article was chosen for presentation at the Health
Law Scholars Workshop, sponsored by the American Society for Law,
Medicine, & Ethics and SLU's Center for Health Law Studies. I am very
thankful for excellent comments from workshop participants. I am
especially grateful to Kathy Cerminara, Annette Clark, Kelly Dineen,
Rebecca Dresser, Jim DuBois, Phil Peters, Christina Wells, and Robin
Fretwell Wilson for providing extensive and helpful feedback. For many
helpful conversations and medical knowledge, I thank Y. Bernard Su and
Christopher Bruno. I also thank my colleagues participating in a
workshop at the University of Missouri.
NR 73
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U1 3
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1073-1105
EI 1748-720X
J9 J LAW MED ETHICS
JI J. Law Med. Ethics
PD SPR
PY 2013
VL 41
IS 1
SI SI
BP 333
EP 352
DI 10.1111/jlme.12024
PG 20
WC Ethics; Law; Medical Ethics; Medicine, Legal
SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal
Medicine
GA 130IY
UT WOS:000317909200024
PM 23581676
ER
PT J
AU George, SM
Alfano, CM
Smith, AW
Irwin, ML
McTiernan, A
Bernstein, L
Baumgartner, KB
Ballard-Barbash, R
AF George, Stephanie M.
Alfano, Catherine M.
Smith, Ashley Wilder
Irwin, Melinda L.
McTiernan, Anne
Bernstein, Leslie
Baumgartner, Kathy B.
Ballard-Barbash, Rachel
TI Sedentary Behavior, Health-Related Quality of Life, and Fatigue Among
Breast Cancer Survivors
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE health behavior; survivorship; epidemiology
ID TELEVISION VIEWING TIME; PHYSICAL-ACTIVITY; EATING INDEX-2005;
LEISURE-TIME; MORTALITY; ADULTS; DIAGNOSIS; ADIPOSITY; CARCINOMA;
EXERCISE
AB Background: Many cancer survivors experience declines in health-related quality of life (HRQOL) and increases in fatigue as a result of cancer and its treatment. Exercise is linked to improvements in these outcomes, but little is known about the role of sedentary behavior. In a large, ethnically-diverse cohort of breast cancer survivors, we examined the relationship between sedentary time, HRQOL, and fatigue, and examined if that relationship differed by recreational moderate-vigorous physical activity (MVPA) level. Methods: Participants were 710 women diagnosed with stage 0-IIIA breast cancer in the Health, Eating, Activity, and Lifestyle Study. Women completed questionnaires at approximately 30-months postdiagnosis (sedentary time; recreational MVPA) and 41-months postdiagnosis (HRQOL; fatigue). In multivariate models, we regressed these outcomes linearly on quartiles of daily sedentary time, and a variable jointly reflecting sedentary time quartiles and MVPA categories (0; >0 to <9; >= 9 MET-hrs/wk). Results: Sedentary time was not independently related to subscales or summary scores of HRQOL or fatigue. In addition, comparisons of women with high vs. low (Q4:Q1) sedentary time by MVPA level did not result in significant differences in HRQOL or fatigue. Conclusion: In this breast cancer survivor cohort, self-reported sedentary time was not associated with HRQOL or fatigue, 3.5 years postdiagnosis.
C1 [George, Stephanie M.; Ballard-Barbash, Rachel] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA.
[Smith, Ashley Wilder] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Irwin, Melinda L.] Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA.
[McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth, Seattle, WA 98104 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA 91010 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
[Baumgartner, Kathy B.] Univ Louisville, Dept Epidemiol & Publ Hlth, Louisville, KY 40292 USA.
RP George, SM (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
FU NCI NIH HHS [N01 PC067010, N01-CN-75036-20, N01 CN005228, K05 CA136967,
N01-CN-05228]
NR 52
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Z9 9
U1 3
U2 13
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD MAR
PY 2013
VL 10
IS 3
BP 350
EP 358
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 135BP
UT WOS:000318261300006
PM 22820125
ER
PT J
AU Ozturk, A
Aygun, N
Smith, SA
Caffo, B
Calabresi, PA
Reich, DS
AF Ozturk, Arzu
Aygun, Nafi
Smith, Seth A.
Caffo, Brian
Calabresi, Peter A.
Reich, Daniel S.
TI Axial 3D gradient-echo imaging for improved multiple sclerosis lesion
detection in the cervical spinal cord at 3T
SO NEURORADIOLOGY
LA English
DT Article
DE Multiple sclerosis; Diagnostic imaging; Magnetic resonance imaging;
Spinal cord; Magnetization transfer contrast imaging
ID INVERSION-RECOVERY MR; MAGNETIZATION-TRANSFER; MULTIARRAY COILS;
WHITE-MATTER; 1.5 T; ARTIFACTS; BRAIN; SEQUENCES; DISEASE; ABNORMALITIES
AB In multiple sclerosis (MS), spinal cord imaging can help in diagnosis and follow-up evaluation. However, spinal cord magnetic resonance imaging (MRI) is technically challenging, and image quality, particularly in the axial plane, is typically poor compared to brain MRI. Because gradient-recalled echo (GRE) images might offer improved contrast resolution within the spinal cord at high magnetic field strength, both without and with a magnetization transfer prepulse, we compared them to T2-weighted fast-spin-echo (T2-FSE) images for the detection of MS lesions in the cervical cord at 3T.
On a clinical 3T MRI scanner, we studied 62 MS cases and 19 healthy volunteers. Axial 3D GRE sequences were performed without and with off-resonance radiofrequency irradiation. To mimic clinical practice, all images were evaluated in conjunction with linked images from a sagittal short tau inversion recovery scan, which is considered the gold standard for lesion detection in MS. Two experienced observers recorded image quality, location and size of focal lesions, atrophy, swelling, and diffuse signal abnormality independently at first and then in consensus.
The number and volume of lesions detected with high confidence was more than three times as high on both GRE sequences compared to T2-FSE (p < 0.0001). Approximately 5 % of GRE scans were affected by artifacts that interfered with image interpretation, not significantly different from T2W-FSE.
Axial 3D GRE sequences are useful for MS lesion detection when compared to 2D T2-FSE sequences in the cervical spinal cord at 3T and should be considered when examining intramedullary spinal cord lesions.
C1 [Ozturk, Arzu; Aygun, Nafi; Reich, Daniel S.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21287 USA.
[Smith, Seth A.] Kennedy Krieger Inst, FM Kirby Res Ctr Funct Brain Imaging, Baltimore, MD 21205 USA.
[Caffo, Brian; Reich, Daniel S.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.
[Calabresi, Peter A.; Reich, Daniel S.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA.
[Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, NIH, Bethesda, MD 20892 USA.
RP Reich, DS (reprint author), NINDS, Translat Neuroradiol Unit, NIH, Bldg 10,Rm 5C103,10 Ctr Dr,MSC 1400, Bethesda, MD 20892 USA.
EM daniel.reich@nih.gov
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU NIH [P41RR015241, K99NS064098]; National Multiple Sclerosis Society
[CA1029A2, TR3760A3]; Nancy Davis Center without Walls; NINDS
FX We thank Terri Brawner, Jonathan Farrell, Eliza Gordon-Lipkin, Kathleen
Kahl, Ivana Kusevic, and Peter van Zijl for assistance with data
collection, and Govind Nair and Jiwon Oh for critical comments on the
manuscript. Funding sources include NIH grants P41RR015241 and
K99NS064098; National Multiple Sclerosis Society grants CA1029A2 and
TR3760A3; and the Nancy Davis Center without Walls. Dr. Reich is
supported by the Intramural Research Program of NINDS.
NR 48
TC 10
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U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-3940
J9 NEURORADIOLOGY
JI Neuroradiology
PD MAR
PY 2013
VL 55
IS 4
BP 431
EP 439
DI 10.1007/s00234-012-1118-5
PG 9
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 132CI
UT WOS:000318045000007
PM 23208410
ER
PT J
AU Tachiwana, H
Miya, Y
Shono, N
Ohzeki, JI
Osakabe, A
Otake, K
Larionov, V
Earnshaw, WC
Kimura, H
Masumoto, H
Kurumizaka, H
AF Tachiwana, Hiroaki
Miya, Yuta
Shono, Nobuaki
Ohzeki, Jun-ichirou
Osakabe, Akihisa
Otake, Koichiro
Larionov, Vladimir
Earnshaw, William C.
Kimura, Hiroshi
Masumoto, Hiroshi
Kurumizaka, Hitoshi
TI Nap1 regulates proper CENP-B binding to nucleosomes
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID HUMAN CENTROMERE PROTEIN; HISTONE CHAPERONE NAP1; OUTER KINETOCHORE;
CHROMOSOME SEGREGATION; CRYSTAL-STRUCTURE; BUDDING YEAST; A NUCLEOSOME;
ALPHOID DNA; IN-VITRO; COMPLEX
AB CENP-B is a widely conserved centromeric satellite DNA-binding protein, which specifically binds to a 17-bp DNA sequence known as the CENP-B box. CENP-B functions positively in the de novo assembly of centromeric nucleosomes, containing the centromere-specific histone H3 variant, CENP-A. At the same time, CENP-B also prevents undesired assembly of the CENP-A nucleosome through heterochromatin formation on satellite DNA integrated into ectopic sites. Therefore, improper CENP-B binding to chromosomes could be harmful. However, no CENP-B eviction mechanism has yet been reported. In the present study, we found that human Nap1, an acidic histone chaperone, inhibited the non-specific binding of CENP-B to nucleosomes and apparently stimulated CENP-B binding to its cognate CENP-B box DNA in nucleosomes. In human cells, the CENP-B eviction activity of Nap1 was confirmed in model experiments, in which the CENP-B binding to a human artificial chromosome or an ectopic chromosome locus bearing CENP-B boxes was significantly decreased when Nap1 was tethered near the CENP-B box sequence. In contrast, another acidic histone chaperone, sNASP, did not promote CENP-B eviction in vitro and in vivo and did not stimulate specific CENP-B binding to CENP-A nucleosomes in vitro. We therefore propose a novel mechanism of CENP-B regulation by Nap1.
C1 [Tachiwana, Hiroaki; Miya, Yuta; Osakabe, Akihisa; Kurumizaka, Hitoshi] Waseda Univ, Grad Sch Adv Sci & Engn, Struct Biol Lab, Shinjuku Ku, Tokyo 1628480, Japan.
[Shono, Nobuaki; Ohzeki, Jun-ichirou; Otake, Koichiro; Masumoto, Hiroshi] Kazusa DNA Res Inst, Dept Human Genome Res, Lab Cell Engn, Kisarazu, Chiba 2920818, Japan.
[Shono, Nobuaki; Otake, Koichiro] Nagoya Univ, Grad Sch Sci, Div Biol Sci, Chikusa Ku, Nagoya, Aichi 4648602, Japan.
[Larionov, Vladimir] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
[Earnshaw, William C.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
[Kimura, Hiroshi] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan.
RP Kurumizaka, H (reprint author), Waseda Univ, Grad Sch Adv Sci & Engn, Struct Biol Lab, Shinjuku Ku, 2-2 Wakamatsu Cho, Tokyo 1628480, Japan.
EM masumoto@kazusa.or.jp; kurumizaka@waseda.jp
RI Shono, Nobuaki/C-4130-2017;
OI Shono, Nobuaki/0000-0002-9060-1074; Kimura, Hiroshi/0000-0003-0854-083X
FU Japanese Society for the Promotion of Science (JSPS); Ministry of
Education, Culture, Sports, Science and Technology (MEXT), Japan; Waseda
Research Institute for Science and Engineering; Sagawa Foundation for
Promotion of Cancer Research; NOVARTIS Foundation (Japan) for the
Promotion of Science; Kazusa DNA Research Institute Foundation; NIH,
NCI, CCR; Wellcome Trust [073915]; Wellcome Trust Centre for Cell
Biology [077707, 092076]; Waseda University
FX Grants-in-Aid from the Japanese Society for the Promotion of Science
(JSPS); Ministry of Education, Culture, Sports, Science and Technology
(MEXT), Japan (in part); Waseda Research Institute for Science and
Engineering, the Sagawa Foundation for Promotion of Cancer Research, and
NOVARTIS Foundation (Japan) for the Promotion of Science (to H. K.);
Kazusa DNA Research Institute Foundation (to H. M.); Intramural Research
Program of the NIH, NCI, CCR (to V. L.). Work in the WCE lab is funded
by The Wellcome Trust, of which WCE is a Principal Research Fellow
[073915]; Wellcome Trust Centre for Cell Biology [077707 and 092076].
Funding for open access charge: Waseda University.
NR 69
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U1 0
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD MAR
PY 2013
VL 41
IS 5
BP 2869
EP 2880
DI 10.1093/nar/gks1464
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 132JB
UT WOS:000318062600015
PM 23325853
ER
PT J
AU Lim, SJ
Boyle, PJ
Chinen, M
Dale, RK
Lei, EP
AF Lim, Su Jun
Boyle, Patrick J.
Chinen, Madoka
Dale, Ryan K.
Lei, Elissa P.
TI Genome-wide localization of exosome components to active promoters and
chromatin insulators in Drosophila
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID RNA-POLYMERASE-II; CRYPTIC UNSTABLE TRANSCRIPTS; LARGE GENE LISTS;
MESSENGER-RNA; BIDIRECTIONAL PROMOTERS; NUCLEAR-ORGANIZATION; ENHANCER
BLOCKING; BITHORAX COMPLEX; BINDING PROTEINS; QUALITY-CONTROL
AB Chromatin insulators are functionally conserved DNA-protein complexes situated throughout the genome that organize independent transcriptional domains. Previous work implicated RNA as an important cofactor in chromatin insulator activity, although the precise mechanisms are not yet understood. Here we identify the exosome, the highly conserved major cellular 3' to 5' RNA degradation machinery, as a physical interactor of CP190-dependent chromatin insulator complexes in Drosophila. Genome-wide profiling of exosome by ChIP-seq in two different embryonic cell lines reveals extensive and specific overlap with the CP190, BEAF-32 and CTCF insulator proteins. Colocalization occurs mainly at promoters but also boundary elements such as Mcp, Fab-8, scs and scs', which overlaps with a promoter. Surprisingly, exosome associates primarily with promoters but not gene bodies of active genes, arguing against simple cotranscriptional recruitment to RNA substrates. Similar to insulator proteins, exosome is also significantly enriched at divergently transcribed promoters. Directed ChIP of exosome in cell lines depleted of insulator proteins shows that CTCF is required specifically for exosome association at Mcp and Fab-8 but not other sites, suggesting that alternate mechanisms must also contribute to exosome chromatin recruitment. Taken together, our results reveal a novel positive relationship between exosome and chromatin insulators throughout the genome.
C1 [Lim, Su Jun; Boyle, Patrick J.; Chinen, Madoka; Dale, Ryan K.; Lei, Elissa P.] NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Lei, EP (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM leielissa@niddk.nih.gov
OI Dale, Ryan/0000-0003-2664-3744
FU National Institute of Diabetes and Digestive and Kidney Diseases
[DK015602-05]
FX Funding for open access charge: Intramural Program of the National
Institute of Diabetes and Digestive and Kidney Diseases [DK015602-05 to
E.L.].
NR 78
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U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD MAR
PY 2013
VL 41
IS 5
BP 2963
EP 2980
DI 10.1093/nar/gkt037
PG 18
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 132JB
UT WOS:000318062600022
PM 23358822
ER
PT J
AU Chon, H
Sparks, JL
Rychlik, M
Nowotny, M
Burgers, PM
Crouch, RJ
Cerritelli, SM
AF Chon, Hyongi
Sparks, Justin L.
Rychlik, Monika
Nowotny, Marcin
Burgers, Peter M.
Crouch, Robert J.
Cerritelli, Susana M.
TI RNase H2 roles in genome integrity revealed by unlinking its activities
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID AICARDI-GOUTIERES-SYNDROME; SUBSTRATE-SPECIFICITY; TOPOISOMERASE-I;
RIBONUCLEASE H; MACROMOLECULAR CRYSTALLOGRAPHY;
SACCHAROMYCES-CEREVISIAE; CRYSTAL-STRUCTURES; DNA-REPLICATION;
EXCISION-REPAIR; INSTABILITY
AB Ribonuclease H2 (RNase H2) protects genome integrity by its dual roles of resolving transcription-related R-loops and ribonucleotides incorporated in DNA during replication. To unlink these two functions, we generated a Saccharomyces cerevisiae RNase H2 mutant that can resolve R-loops but cannot cleave single ribonucleotides in DNA. This mutant definitively correlates the 2-5 bp deletions observed in rnh201 Delta strains with single rNMPs in DNA. It also establishes a connection between R-loops and Sgs1-mediated replication reinitiation at stalled forks and identifies R-loops uniquely processed by RNase H2. In mouse, deletion of any of the genes coding for RNase H2 results in embryonic lethality, and in humans, RNase H2 hypomorphic mutations cause Aicardi-Goutieres syndrome (AGS), a neuroinflammatory disorder. To determine the contribution of R-loops and rNMP in DNA to the defects observed in AGS, we characterized in yeast an AGS-related mutation, which is impaired in processing both substrates, but has sufficient R-loop degradation activity to complement the defects of rnh201 Delta sgs1 Delta strains. However, this AGS-related mutation accumulates 2-5 bp deletions at a very similar rate as the deletion strain.
C1 [Chon, Hyongi; Crouch, Robert J.; Cerritelli, Susana M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, Bethesda, MD 20892 USA.
[Sparks, Justin L.; Burgers, Peter M.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
[Rychlik, Monika; Nowotny, Marcin] Int Inst Mol & Cell Biol, Lab Prot Struct, PL-02109 Warsaw, Poland.
RP Crouch, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, Bethesda, MD 20892 USA.
EM Robert_crouch@nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health; National Institutes of
Health [GM032431]; Wellcome Trust [081760]
FX Intramural Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health (in
part); National Institutes of Health [GM032431, in part] to P. M. B.;
Wellcome Trust International Senior Research Fellowship [081760 to
M.N.]. M.N. is an HHMI International Early Career Scholar. Funding for
open access charge: Intramural Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health.
NR 54
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U1 0
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD MAR
PY 2013
VL 41
IS 5
BP 3130
EP 3143
DI 10.1093/nar/gkt027
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 132JB
UT WOS:000318062600035
PM 23355612
ER
PT J
AU He, SS
Guynet, C
Siguier, P
Hickman, AB
Dyda, F
Chandler, M
Bao, TH
AF He, Susu
Guynet, Catherine
Siguier, Patricia
Hickman, Alison B.
Dyda, Fred
Chandler, Mick
Bao Ton-Hoang
TI IS200/IS605 family single-strand transposition: mechanism of IS608
strand transfer
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID DNA TRANSPOSITION; SEQUENCE; RECONSTITUTION; TRANSPOSASES; RECOGNITION
AB Transposase, TnpA, of the IS200/IS605 family member IS608, catalyses single-strand DNA transposition and is dimeric with hybrid catalytic sites composed of an HUH motif from one monomer and a catalytic Y127 present in an alpha-helix (alpha D) from the other (trans configuration). alpha D is attached to the main body by a flexible loop. Although the reactions leading to excision of a transposition intermediate are well characterized, little is known about the dynamic behaviour of the transpososome that drives this process. We provide evidence strongly supporting a strand transfer model involving rotation of both alpha D helices from the trans to the cis configuration (HUH and Y residues from the same monomer). Studies with TnpA heterodimers suggest that TnpA cleaves DNA in the trans configuration, and that the catalytic tyrosines linked to the 5'-phosphates exchange positions to allow rejoining of the cleaved strands (strand transfer) in the cis configuration. They further imply that, after excision of the transposon junction, TnpA should be reset to a trans configuration before the cleavage required for integration. Analysis also suggests that this mechanism is conserved among members of the IS200/IS605 family.
C1 [He, Susu; Guynet, Catherine; Siguier, Patricia; Chandler, Mick; Bao Ton-Hoang] CNRS, Unite Mixte Rech 5100, Lab Microbiol & Genet Mol, F-31062 Toulouse, France.
[Hickman, Alison B.; Dyda, Fred] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Bao, TH (reprint author), CNRS, Unite Mixte Rech 5100, Lab Microbiol & Genet Mol, 118 Rte Narbonne, F-31062 Toulouse, France.
EM Michael.Chandler@ibcg.biotoul.fr; Tonhoang@ibcg.biotoul.fr
OI Chandler, Michael/0000-0002-0292-6662
FU Centre National de Recherche Scientifique (CNRS, France); ANR [ANR08
Blanc-0336 Mobigen]; National Institute of Diabetes and Digestive and
Kidney Diseases; CNRS
FX Centre National de Recherche Scientifique (CNRS, France); by ANR [ANR08
Blanc-0336 Mobigen to M. C]; intramural Program of the National
Institute of Diabetes and Digestive and Kidney Diseases (to F. D).
Funding for open access charge: CNRS intramural funding.
NR 15
TC 11
Z9 11
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD MAR
PY 2013
VL 41
IS 5
BP 3302
EP 3313
DI 10.1093/nar/gkt014
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 132JB
UT WOS:000318062600047
PM 23345619
ER
PT J
AU Lublin, FD
Cofield, SS
Cutter, GR
Conwit, R
Narayana, PA
Nelson, F
Salter, AR
Gustafson, T
Wolinsky, JS
AF Lublin, Fred D.
Cofield, Stacey S.
Cutter, Gary R.
Conwit, Robin
Narayana, Ponnada A.
Nelson, Flavia
Salter, Amber R.
Gustafson, Tarah
Wolinsky, Jerry S.
CA CombiRx Investigators
TI Randomized study combining interferon and glatiramer acetate in multiple
sclerosis
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID BRAIN ATROPHY; MS; TRIAL; MRI; SEGMENTATION; MECHANISMS; THERAPIES;
DISEASE; VOLUME
AB Objective A double-blind, randomized, controlled study was undertaken to determine whether combined use of interferon -1a (IFN) 30g intramuscularly weekly and glatiramer acetate (GA) 20mg daily is more efficacious than either agent alone in relapsingremitting multiple sclerosis. Methods A total of 1,008 participants were randomized and followed until the last participant enrolled completed 3 years. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score, and magnetic resonance imaging (MRI) metrics. Results Combination IFN+GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The combination was not better than either agent alone in lessening confirmed Expanded Disability Status Scale progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity-free status (DAFS) compared to either single arm, driven by the MRI results. Interpretation Combining the 2 most commonly prescribed therapies for multiple sclerosis did not produce a significant clinical benefit over 3 years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address whether the observed differences in MRI and DAFS findings predict later clinical differences. ANN NEUROL 2013;73:327340
C1 [Lublin, Fred D.; Gustafson, Tarah] Icahn Sch Med Mt Sinai, Corinne Goldsmith Dickinson Ctr Multiple Sclerosi, Dept Neurol, New York, NY USA.
[Lublin, Fred D.; Gustafson, Tarah] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY USA.
[Cofield, Stacey S.; Cutter, Gary R.; Salter, Amber R.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
[Conwit, Robin] NINDS, NIH, Bethesda, MD 20892 USA.
[Narayana, Ponnada A.] Univ Texas Hlth Sci Ctr Houston, Dept Diagnost & Intervent Imaging, Houston, TX USA.
[Nelson, Flavia; Wolinsky, Jerry S.] Univ Texas Hlth Sci Ctr Houston, Dept Neurol, Houston, TX USA.
RP Lublin, FD (reprint author), 5 East 98th St, New York, NY 10029 USA.
EM fred.lublin@mssm.edu
FU NIH National Institute of Neurological Disorders and Stroke
[UO1NS045719, R21NS41986]; Celgene; Sanofi-Aventis; Acorda; Novartis;
EMD Serono; Pfizer; Teva; Teva Neuroscience; National Multiple Sclerosis
Society; CMSC; MS Monitor; Biogen Idec; Bayer HealthCare; Mesdcape
Radiology, Projects in Knowledge; Clayton Foundation for Research;
NIH/NINDS; NIH/NIBIB; Consortium MS Centers; USF; Texas Neurological
Society; Teva Pharmaceuticals; Medscape CME; University of Buffalo;
Serono Symposia International Foundation; University of Utah; NINDS;
Prime
FX This study was funded by the NIH National Institute of Neurological
Disorders and Stroke (phase III study grant UO1NS045719, planning grant
R21NS41986) and is listed on www.clinicaltrials.gov as NCT00211887.
Study agents and matched placebo were kindly provided by their
manufacturers, Biogen Idec and Teva Pharmaceutical.; F.D.L.:
consultancy, Biogen Idec, Teva Neuroscience, Bayer HealthCare, EMD
Serono, Novartis, Pfizer, Actelion, Sanofi-Aventis, Acorda, Questcor,
Roche, Genentech, Celgene, Johnson & Johnson, Revalesio, Coronado
Bioscience, Genzyme, MedImmune, Abbott, Bristol-Myers Squibb, Xenoport,
Medicinova, Genmab, Morphosys, Avanir, Kyowa Hakko Kirin, Receptos;
grants/grants pending, Celgene, Sanofi-Aventis, Acorda, Novartis;
speaking fees, EMD Serono, Pfizer, Teva. S.S.C.: consultancy, Teva
Neuroscience, American Shoulder and Elbow Society, MedImmune, Manitoba
Health Research Council, Centocor Ortho Biotech; paid educational
presentations, Teva Neuroscience. G.R.C.: grants/grants pending,
National Multiple Sclerosis Society; board membership, Pythagoras;
consultancy, Biogen Idec, Teva Neuroscience, Bayer HealthCare, EMD
Serono, Novartis, Pfizer, Sanofi-Aventis, Questcor, Celgene, Revalesio,
Coronado Bioscience, Genzyme, MedImmune, Abbott, Receptos, Gilead,
Neuren, Apotex/Modigenetec, NHLBI, NICHD, Ono/Merck, Merck, Nuron
Biotech, Somnus, Spinifex, United Bioscience, Cleveland Clinic, Vivus,
GlaxoSmithKlein; speaking fees, CMSC, Novartis, Teva; paid educational
presentations, MS Monitor. F.N.: consultancy, Bayer HealthCare, Biogen
Idec, MS Society, Genentech, Sanofi-Aventis, Teva Neuroscience,
Novartis; grants/grants pending, Novartis; speaking fees, Biogen Idec,
Bayer HealthCare; paid educational presentations, Mesdcape Radiology,
Projects in Knowledge. J.S.W.: board membership, Novartis
Pharmaceuticals, Sanofi-Aventis, Teva Pharmaceuticals, Eli Lilly, BC
Decker; consultancy, Genentech, Novartis Pharmaceuticals, Teva
Neuroscience, Teva Pharmaceuticals, Acorda, Acetilon, Bayer HealthCare,
Celgene, Astellas, Hoffman LaRoche, Janssen R & D; grants/grants
pending, Sanofi-Aventis, Clayton Foundation for Research, National
Multiple Sclerosis Society, NIH/NINDS, NIH/NIBIB; speaking fees,
Consortium MS Centers, USF Health Professionals, Texas Neurological
Society, Teva Pharmaceuticals, Medscape CME, University of Buffalo,
Serono Symposia International Foundation, University of Utah, Biogen
Idec, NINDS, Prime; royalties, Millipore (Chemicon International) Corp.
NR 22
TC 74
Z9 75
U1 0
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD MAR
PY 2013
VL 73
IS 3
BP 327
EP 340
DI 10.1002/ana.23863
PG 14
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 131KW
UT WOS:000317992900004
PM 23424159
ER
PT J
AU Liu, DP
Zhou, XH
AF Liu, Danping
Zhou, Xiao-Hua
TI Covariate Adjustment in Estimating the Area Under ROC Curve with
Partially Missing Gold Standard
SO BIOMETRICS
LA English
DT Article
DE Alzheimer's disease; Area under ROC curve; Covariate adjustment; U
statistics; Verification bias; Weighted estimating equations
ID OPERATING CHARACTERISTIC CURVE; NONIGNORABLE VERIFICATION BIAS;
DIAGNOSTIC-TESTS; DISEASE; ACCURACY
AB In ROC analysis, covariate adjustment is advocated when the covariates impact the magnitude or accuracy of the test under study. Meanwhile, for many large scale screening tests, the true condition status may be subject to missingness because it is expensive and/or invasive to ascertain the disease status. The complete-case analysis may end up with a biased inference, also known as verification bias. To address the issue of covariate adjustment with verification bias in ROC analysis, we propose several estimators for the area under the covariate-specific and covariate-adjusted ROC curves (AUCx and AAUC). The AUCx is directly modeled in the form of binary regression, and the estimating equations are based on the U statistics. The AAUC is estimated from the weighted average of AUCx over the covariate distribution of the diseased subjects. We employ reweighting and imputation techniques to overcome the verification bias problem. Our proposed estimators are initially derived assuming that the true disease status is missing at random (MAR), and then with some modification, the estimators can be extended to the not missing at random (NMAR) situation. The asymptotic distributions are derived for the proposed estimators. The finite sample performance is evaluated by a series of simulation studies. Our method is applied to a data set in Alzheimer's disease research.
C1 [Liu, Danping] Univ Washington, Natl Alzheimers Coordinating Ctr, Seattle, WA 98195 USA.
[Zhou, Xiao-Hua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
[Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
RP Liu, DP (reprint author), Univ Washington, Natl Alzheimers Coordinating Ctr, Seattle, WA 98195 USA.
EM azhou@uw.edu; danping.liu@nih.gov
FU NIH/NIA [U01AG016976]; National Institute of Health (NIH), Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD)
FX The authors would like to thank National Alzheimer's Coordinating Center
(NACC) for providing the data for analysis. The authors are grateful to
the associate editor and two anonymous referees for their insightful
comments, which greatly improved the quality of this paper. The work was
supported in part by NIH/NIA grant U01AG016976. The research of Dr.
Danping Liu is supported in part 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 article
does not necessarily represent the findings and conclusions of VA HSR&D.
Dr. Xiao-Hua Zhou is presently a Core Investigator and Biostatistics
Unit Director at HSR&D Center of Excellence, Department of Veterans
Affairs Puget Sound Health Care System, Seattle, WA.
NR 16
TC 3
Z9 3
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2013
VL 69
IS 1
BP 91
EP 100
DI 10.1111/biom.12001
PG 10
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 122FM
UT WOS:000317303500010
PM 23410529
ER
PT J
AU Kinsella, K
Beard, J
Suzman, R
AF Kinsella, Kevin
Beard, John
Suzman, Richard
TI Can Populations Age Better, Not Just Live Longer?
SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING
LA English
DT Article
ID LAST YEAR; LIFE; COSTS; DISADVANTAGE; DISABILITY; DISEASE; HEALTH;
TRENDS
C1 [Kinsella, Kevin] CNR, Comm Populat, Washington, DC 20418 USA.
[Beard, John] WHO, Dept Ageing & Life Course, CH-1211 Geneva, Switzerland.
[Suzman, Richard] NIA, Div Behav & Social Res, NIH, Washington, DC USA.
RP Kinsella, K (reprint author), CNR, Comm Populat, Washington, DC 20418 USA.
RI Beard, John/K-9621-2014
OI Beard, John/0000-0002-8557-0242
NR 26
TC 2
Z9 2
U1 0
U2 1
PU AMER SOC AGING
PI SAN FRANCISCO
PA 833 MARKET ST, STE 511, SAN FRANCISCO, CA 94103-1824 USA
SN 0738-7806
J9 GENERATIONS
JI Generations-J. Am. Soc. Aging
PD SPR
PY 2013
VL 37
IS 1
BP 19
EP 26
PG 8
WC Gerontology
SC Geriatrics & Gerontology
GA 125US
UT WOS:000317567500004
ER
PT J
AU McIver, Z
Melenhorst, JJ
Wu, C
Grim, A
Ito, S
Cho, I
Hensel, N
Battiwalla, M
Barrett, AJ
AF McIver, Zachariah
Melenhorst, Jan Joseph
Wu, Colin
Grim, Andrew
Ito, Sawa
Cho, Irene
Hensel, Nancy
Battiwalla, Minoo
Barrett, Austin John
TI Donor lymphocyte count and thymic activity predict lymphocyte recovery
and outcomes after matched-sibling hematopoietic stem cell transplant
SO HAEMATOLOGICA
LA English
DT Article
ID REGULATORY T-CELLS; VERSUS-HOST-DISEASE; SUPPRESSIVE FUNCTION; IMMUNE
RECONSTITUTION; PERIPHERAL-BLOOD; RISK-FACTORS; BONE-MARROW; RECIPIENTS;
ANTIGEN; EXPRESSION
AB Delayed immune recovery is a characteristic feature of allogeneic hematopoietic stem cell transplantation in adult recipients. Although recipient thymic T-cell neogenesis contributes to T-cell regeneration after transplantation, thymic recovery in the transplant recipient decreases with increasing age, and is diminished by intensive preconditioning regimens and graft-versus-host disease. In adult recipients, most events that determine transplant success or failure occur during the period when the majority of circulating T cells is derived from the donor's post thymic T-cell repertoire. As a result, the make-up of the donor lymphocyte compartment may strongly influence immune recovery and transplant outcomes. The aim of this study was to examine donor lymphocyte counts in a series of patients undergoing an allogeneic hematopoietic stem cell transplant to identify the potential contribution of donor regulatory and conventional T lymphocyte populations to immune recovery and transplant outcomes. We examined donor lymphocyte subset counts in relation to post-transplant lymphocyte recovery and transplant events in 220 consecutive myeloablative, T-cell-depleted, HLA-identical sibling hematopoietic stem cell transplant recipients with hematologic malignancies. In a multivariate analysis, absolute numbers of donor CD4(+) recent thymic emigrants were associated with overall survival (P=0.032). The donors' absolute lymphocyte count and thymic production of regulatory T cells were both associated with extensive chronic graft-versus-host disease (P=0.002 and P=0.022, respectively). In conclusion, these results identify donor immune characteristics that are associated with lymphocyte recovery, extensive chronic graft-versus-host disease, and survival in the recipient following allogeneic hematopoietic stem cell transplantation. The study reported here was performed using peripheral blood samples drawn from donors and patients enrolled in the ClinicalTrials.gov-registered trials NCT00001623, NCT00001873, NCT00353860, NCT00066300, NCT00079391, and NCT00398346.
C1 [McIver, Zachariah; Melenhorst, Jan Joseph; Grim, Andrew; Ito, Sawa; Cho, Irene; Hensel, Nancy; Battiwalla, Minoo; Barrett, Austin John] NHLBI, Allogene Stem Cell Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Wu, Colin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
RP McIver, Z (reprint author), NHLBI, Allogene Stem Cell Transplantat Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM mej@mail.med.upenn.edu
NR 37
TC 7
Z9 7
U1 0
U2 10
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD MAR
PY 2013
VL 98
IS 3
BP 346
EP 352
DI 10.3324/haematol.2012.072991
PG 7
WC Hematology
SC Hematology
GA 125HJ
UT WOS:000317530600005
PM 23065508
ER
PT J
AU Nekhai, S
Xu, M
Foster, A
Kasvosve, I
Diaz, S
Machado, RF
Castro, OL
Kato, GJ
Taylor, JG
Gordeuk, VR
AF Nekhai, Sergei
Xu, Min
Foster, Altreisha
Kasvosve, Ishmael
Diaz, Sharmin
Machado, Roberto F.
Castro, Oswaldo L.
Kato, Gregory J.
Taylor, James G.
Gordeuk, Victor R.
TI Reduced sensitivity of the ferroportin Q248H mutant to physiological
concentrations of hepcidin
SO HAEMATOLOGICA
LA English
DT Article
ID SICKLE-CELL-DISEASE; REGULATORY PEPTIDE HEPCIDIN; PRIMARY IRON OVERLOAD;
NECROSIS-FACTOR-ALPHA; HUMAN SERUM HEPCIDIN; PULMONARY-HYPERTENSION;
AFRICAN-AMERICANS; HEREDITARY HEMOCHROMATOSIS; J774 MACROPHAGES;
RISK-FACTOR
AB Ferroportin Q248H mutation has an allele frequency of 2.2-13.4% in African populations and is associated with a mild tendency to increased serum ferritin in the general population. Some investigators have reported that ferroportin Q248H is degraded after exposure to hepcidin in exactly the same manner as wild-type ferroportin, but supraphysiological concentrations of hepcidin were used. The aim of our study was to determine whether ferroportin Q248H may have reduced sensitivity to physiological concentrations of hepcidin. The sensitivity of ferroportin Q248H to hepcidin was determined in 293T cells transiently expressing ferroportin using immunoblotting and fluorescence analysis. Ferritin concentrations were measured in these cells and also in human primary monocytes derived from humans with different ferroportin genotypes. The effect of Q248H on serum iron measures was examined in patients with sickle cell anemia. Immunoblotting and fluorescence analysis showed decreased sensitivity of ferroportin Q248H to physiological concentrations of hepcidin. Lower ferritin concentrations were observed after incubation with iron and hepcidin in 293T cells expressing ferroportin Q248H and in primary monocytes from ferroportin Q248H subjects. In sickle cell anemia, ferroportin Q248H heterozygotes had lower serum ferritin concentrations than wild-type subjects, consistent with enhanced iron release by macrophage ferroportin Q248H. A clinical benefit of ferroportin Q248H was suggested by lower echocardiographic estimates of pulmonary artery pressure in patients carrying mutant alleles. In conclusion, our results suggest that ferroportin Q248H protein is resistant to physiological concentrations of hepcidin and that this mutation has discernible effects on iron metabolism-related clinical complications of sickle cell anemia. They provide a mechanistic explanation for the effect of ferroportin Q248H on iron status in individuals of African descent and suggest that these changes in iron metabolism may be beneficial under certain disease-specific circumstances. (ClinicalTrials.gov Identifier:NCT00011648).
C1 [Nekhai, Sergei; Xu, Min; Foster, Altreisha; Diaz, Sharmin; Castro, Oswaldo L.; Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Dept Med, Washington, DC 20059 USA.
[Kasvosve, Ishmael] Univ Botswana, Dept Med Lab Sci, Gaborone, Botswana.
[Machado, Roberto F.; Gordeuk, Victor R.] Univ Illinois, Sickle Cell Ctr, Chicago, IL USA.
[Kato, Gregory J.; Taylor, James G.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Nekhai, S (reprint author), Howard Univ, Ctr Sickle Cell Dis, Dept Med, Washington, DC 20059 USA.
EM snekhai@howard.edu; vgordeuk@uic.edu
RI Kato, Gregory/I-7615-2014;
OI Kato, Gregory/0000-0003-4465-3217; Taylor, James/0000-0002-4421-1809
FU NIH [1SC1GM082325, R25 HL003679, RCMI-NIH 2G12RR003048, P30HL107253, R01
HL079912, 2MOI RR10284]; District of Columbia Developmental Center for
AIDS Research Grant [P30AI087714]; NHLBI Division of Intramural Research
[1ZIAHL006012-03]
FX This work was supported by NIH Research Grants (1SC1GM082325, R25
HL003679, RCMI-NIH 2G12RR003048, P30HL107253, R01 HL079912, 2MOI
RR10284) District of Columbia Developmental Center for AIDS Research
Grant (P30AI087714), and by the NHLBI Division of Intramural Research
(1ZIAHL006012-03).
NR 68
TC 10
Z9 10
U1 0
U2 4
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD MAR
PY 2013
VL 98
IS 3
BP 455
EP 463
DI 10.3324/haematol.2012.066530
PG 9
WC Hematology
SC Hematology
GA 125HJ
UT WOS:000317530600025
PM 23065513
ER
PT J
AU Nourale, M
Lee, JS
Zhang, YZ
Kanias, T
Zhao, XJ
Xiong, ZY
Oriss, TB
Zeng, QL
Kato, GJ
Gibbs, JSR
Hildesheim, ME
Sachdev, V
Barst, RJ
Machado, RF
Hassell, KL
Little, JA
Schraufnagel, DE
Krishnamurti, L
Novelli, E
Girgis, RE
Morris, CR
Rosenzweig, EB
Badesch, DB
Lanzkron, S
Castro, OL
Goldsmith, JC
Gordeuk, VR
Gladwin, MT
AF Nourale, Mehdi
Lee, Janet S.
Zhang, Yingze
Kanias, Tamir
Zhao, Xuejun
Xiong, Zeyu
Oriss, Timothy B.
Zeng, Qilu
Kato, Gregory J.
Gibbs, J. Simon R.
Hildesheim, Mariana E.
Sachdev, Vandana
Barst, Robyn J.
Machado, Roberto F.
Hassell, Kathryn L.
Little, Jane A.
Schraufnagel, Dean E.
Krishnamurti, Lakshmanan
Novelli, Enrico
Girgis, Reda E.
Morris, Claudia R.
Rosenzweig, Erika Berman
Badesch, David B.
Lanzkron, Sophie
Castro, Oswaldo L.
Goldsmith, Jonathan C.
Gordeuk, Victor R.
Gladwin, Mark T.
CA Walk-PHASST Investigators Patients
TI The relationship between the severity of hemolysis, clinical
manifestations and risk of death in 415 patients with sickle cell anemia
in the US and Europe
SO HAEMATOLOGICA
LA English
DT Article
ID HEMOGLOBIN OXYGEN DESATURATION; NITRIC-OXIDE BIOAVAILABILITY;
PULMONARY-HYPERTENSION; PULSE OXIMETRY; MICROPARTICLE ENUMERATION;
EXERCISE CAPACITY; CHEST SYNDROME; DISEASE; CHILDREN; ASSOCIATION
AB The intensity of hemolytic anemia has been proposed as an independent risk factor for the development of certain clinical complications of sickle cell disease, such as pulmonary hypertension, hypoxemia and cutaneous leg ulceration. A composite variable derived from several individual markers of hemolysis could facilitate studies of the underlying mechanisms of hemolysis. In this study, we assessed the association of hemolysis with outcomes in sickle cell anemia. A hemolytic component was calculated by principal component analysis from reticulocyte count, serum lactate dehydrogenase, aspartate aminotransferase and total bilirubin concentrations in 415 hemoglobin SS patients. Association of this component with direct markers of hemolysis and clinical outcomes was assessed. As primary validation, both plasma red blood cell microparticles and cell-free hemoglobin concentration were higher in the highest hemolytic component quartile compared to the lowest quartile (P <= 0.0001 for both analyses). The hemolytic component was lower with hydroxyurea therapy, higher hemoglobin F, and alpha-thalassemia (P <= 0.0005); it was higher with higher systemic pulse pressure, lower oxygen saturation, and greater values for tricuspid regurgitation velocity, left ventricular diastolic dimension and left ventricular mass (all P<0.0001). Two-year follow-up analysis showed that a high hemolytic component was associated with an increased risk of death (hazard ratio, HR 3.44; 95% confidence interval, CI: 1.2-9.5; P=0.02). The hemolytic component reflects direct markers of intravascular hemolysis in patients with sickle cell disease and allows for adjusted analysis of associations between hemolytic severity and clinical outcomes. These results confirm associations between hemolytic rate and pulse pressure, oxygen saturation, increases in Doppler-estimated pulmonary systolic pressures and mortality
C1 [Nourale, Mehdi; Castro, Oswaldo L.] Howard Univ, Washington, DC 20059 USA.
[Lee, Janet S.; Zhang, Yingze; Kanias, Tamir; Xiong, Zeyu; Zeng, Qilu; Novelli, Enrico; Gladwin, Mark T.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15260 USA.
[Lee, Janet S.; Kanias, Tamir; Oriss, Timothy B.; Hildesheim, Mariana E.; Gladwin, Mark T.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15260 USA.
[Zhao, Xuejun; Kato, Gregory J.; Sachdev, Vandana] NHLBI, Cardiovasc & Pulm Med Branch, Bethesda, MD 20892 USA.
[Gibbs, J. Simon R.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2AZ, England.
[Barst, Robyn J.; Rosenzweig, Erika Berman] Columbia Univ, New York, NY USA.
[Machado, Roberto F.; Schraufnagel, Dean E.; Gordeuk, Victor R.] Univ Illinois, Chicago, IL USA.
[Hassell, Kathryn L.; Badesch, David B.] Univ Colorado HSC, Denver, CO USA.
[Little, Jane A.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Krishnamurti, Lakshmanan] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
[Girgis, Reda E.; Lanzkron, Sophie] Johns Hopkins Univ, Baltimore, MD USA.
[Morris, Claudia R.] Childrens Hosp & Res Ctr Oakland, Oakland, CA USA.
[Goldsmith, Jonathan C.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Gladwin, MT (reprint author), Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15260 USA.
EM gladwinmt@upmc.edu
RI Kato, Gregory/I-7615-2014; Kanias, Tamir/K-2384-2016;
OI Kato, Gregory/0000-0003-4465-3217; Kanias, Tamir/0000-0001-6558-0913;
Schraufnagel, Dean/0000-0003-0063-7223
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Department of Health and Human Services [HHSN268200617182C]; NIH
CTSA from NHLBI [UL1 RR024131, 2 R25 HL003679-08, 1 R01 HL079912-02];
Howard University GCRC from NCRR, NIH, Bethesda, MD [2MOI RR10284-10];
NIH [R01HL098032, RO1HL096973]; Institute for Transfusion Medicine;
Hemophilia Center of Western Pennsylvania; National Institutes of
Health; [R01HL086884]; [R01HL086884 03S1]
FX This work was supported by funds from the National Heart, Lung, and
Blood Institute, National Institutes of Health, Department of Health and
Human Services, under contract HHSN268200617182C. This work was also
supported in part by NIH CTSA grant UL1 RR024131 (to CRM), grant ns. 2
R25 HL003679-08 and 1 R01 HL079912-02 from NHLBI (to VRG), by Howard
University GCRC grant n. 2MOI RR10284-10 from NCRR, NIH, Bethesda, MD,
by R01HL086884 and R01HL086884 03S1 (to JSL), by NIH grants R01HL098032
and RO1HL096973 (to MTG), by the Institute for Transfusion Medicine and
the Hemophilia Center of Western Pennsylvania and by the intramural
research program of the National Institutes of Health.
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PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD MAR
PY 2013
VL 98
IS 3
BP 464
EP 472
DI 10.3324/haematol.2012.068965
PG 9
WC Hematology
SC Hematology
GA 125HJ
UT WOS:000317530600026
PM 22983573
ER
PT J
AU Yang, WZ
Ye, G
Meng, AH
Sabir, G
Qiao, X
Guo, DA
Ye, M
AF Yang, Wen-zhi
Ye, Guan
Meng, A-hui
Sabir, Gulnar
Qiao, Xue
Guo, De-an
Ye, Min
TI Rapid characterisation of flavonoids from Sophora alopecuroides L. by
HPLC/DAD/ESI-MS (n)
SO NATURAL PRODUCT RESEARCH
LA English
DT Article
DE Sophora alopecuroides L; HPLC; DAD; ESI-MS; (n); characterisation;
flavonoids
ID IONIZATION MASS-SPECTROMETRY; PHENOLIC-COMPOUNDS; AGLYCONES
AB An HPLC/DAD/ESI-MS (n) method was established to characterise flavonoids in the seeds of Sophora alopecuroides L. All the flavonoids exhibited abundant [MH] ions, which triggered data-dependent multistage mass spectrometry fragmentations. Characteristic UV spectra were used to confirm flavonoid subtypes. In total, 22 flavonoids and two phenolic compounds were detected and identified. Five of them were identified by comparing with reference standards, and the others were characterised based on the retention behaviour, multistage fragmentation feature and UV absorption. A total of 19 compounds were reported from S. alopecuroides for the first time. This method accomplished rapid profiling of flavonoid constituents in S. alopecuroides L.
C1 [Yang, Wen-zhi; Qiao, Xue; Guo, De-an; Ye, Min] Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China.
[Ye, Guan] NIH, Bethesda, MD 20892 USA.
[Meng, A-hui] Beijing Forestry Univ, Coll Biol Sci & Biotechnol, Beijing 100083, Peoples R China.
[Sabir, Gulnar] Xinjiang Inst Chinese Mat Med & Eth, Urumqi 830002, Peoples R China.
RP Ye, M (reprint author), Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, 38 Xueyuan Rd, Beijing 100191, Peoples R China.
EM yemin@bjmu.edu.cn
FU Peking University Health Science Center [985-2-119-121]
FX This study was supported by the 985 Project of Peking University Health
Science Center (No. 985-2-119-121).
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U2 25
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1478-6419
J9 NAT PROD RES
JI Nat. Prod. Res.
PD MAR 1
PY 2013
VL 27
IS 4-5
BP 323
EP 330
DI 10.1080/14786419.2012.688052
PG 8
WC Chemistry, Applied; Chemistry, Medicinal
SC Chemistry; Pharmacology & Pharmacy
GA 101SB
UT WOS:000315793600006
PM 22625220
ER
PT J
AU Shariff-Marco, S
Breen, N
Stinchcomb, DG
Klabunde, CN
AF Shariff-Marco, Salma
Breen, Nancy
Stinchcomb, David G.
Klabunde, Carrie N.
TI Multilevel Predictors of Colorectal Cancer Screening Use in California
SO AMERICAN JOURNAL OF MANAGED CARE
LA English
DT Article
ID CARE HEALTH PLAN; BRIEF CONCEPTUAL TUTORIAL; MANAGED CARE;
UNITED-STATES; LOGISTIC-REGRESSION; SOCIAL EPIDEMIOLOGY;
SOCIOECONOMIC-STATUS; CONTEXTUAL PHENOMENA; INTERVIEW SURVEY; POVERTY
RATE
AB Background: Screening can detect colorectal cancer (CRC) early, yet its uptake needs to be improved. Social determinants of health (SDOH) may be linked to CRC screening use but are not well understood.
Objectives: To examine geographic variation in CRC screening and the extent to which multilevel SDOH explain its use in California, the most populous and racially/ethnically diverse state in the United States.
Study Design: Analysis of individual and neighborhood data on 20,626 adult respondents aged years from the 2005 California Health Interview Survey.
Methods: We used multilevel logistic regression models to estimate the effects of individual characteristics and area-level segregation, socioeconomic status (SES), and healthcare resources at 2 different geographic levels on CRC screening use.
Results: We confirmed that individual-level factors (eg, race/ethnicity, income, insurance) were strong predictors and found that area-level healthcare resources were associated with CRC screening. Primary care shortage in the Medical Service Study Area was associated with CRC screening for any modality (odds ratio [OR] = 0.89; 95% confidence interval [Cl], 0.80-1.00). County-level HMO penetration (OR = 1.85; 95% Cl, 1.47-2.33) and primary care shortage (OR = 0.73; 95% CI, 0.53-0.99) were associated with CRC screening with flexible sigmoidoscopy.
Conclusions: Contextual factors including locality, primary care resources, and HMO membership are important determinants of CRC screening uptake; SES and segregation did not explain variation in screening behavior. More studies of contextual factors and varying geographic scales are needed to further elucidate their impact on CRC screening uptake. Am J Manag Care. 2013;19(3):205-216
C1 [Shariff-Marco, Salma] Canc Prevent Inst Calif, Fremont, CA USA.
[Breen, Nancy; Klabunde, Carrie N.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Stinchcomb, David G.] Westat Corp, Rockville, MD USA.
RP Shariff-Marco, S (reprint author), Canc Prevent Inst Calif, 2201 Walnut Ave,Ste 300, Fremont, CA 94538 USA.
EM salma.shariff-marco@cpic.org
FU Cancer Prevention Fellowship Program, Office of Preventive Oncology,
National Cancer Institute
FX We would like to acknowledge the Cancer Prevention Fellowship Program,
Office of Preventive Oncology, National Cancer Institute for providing
financial support for Salma Shariff-Marco in her postdoctoral
fellowship. We would also like to acknowledge Tim McNeel, William
Waldron, and Jeremy Lyman at Information Management Services, Inc, for
their support in merging our data sets, developing programs for the
descriptive analysis, and generating the maps for the Figure; and Penny
Randall-Levy of the Scientific Consulting. Group, Inc, for her help with
the references. Finally, we would like to acknowledge Drs Martin L.
Brown and Rachel Ballard-Barbash for their thoughtful reviews.
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U2 4
PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC
PI PLAINSBORO
PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA
SN 1088-0224
J9 AM J MANAG CARE
JI Am. J. Manag. Care
PD MAR
PY 2013
VL 19
IS 3
BP 205
EP 216
PG 12
WC Health Care Sciences & Services; Health Policy & Services; Medicine,
General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 123GI
UT WOS:000317376000004
PM 23544762
ER
PT J
AU Weyemi, U
Redon, CE
Parekh, PR
Dupuy, C
Bonner, WM
AF Weyemi, Urbain
Redon, Christophe E.
Parekh, Palak R.
Dupuy, Corinne
Bonner, William M.
TI NADPH Oxidases NOXs and DUOXs as Putative Targets for Cancer Therapy
SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
LA English
DT Article
DE NADPH oxidases; ROS; Cancer; Cancer therapy; Tumors; NOXs inhibitors
ID SMOOTH-MUSCLE-CELLS; OXYGEN SPECIES PRODUCTION; ENDOTHELIAL
GROWTH-FACTOR; COLON EPITHELIAL-CELLS; REACTIVE OXYGEN; NAD(P)H OXIDASE;
ESOPHAGEAL ADENOCARCINOMA; DIPHENYLENE IODONIUM; PROSTATE-CANCER;
MELANOMA-CELLS
AB Reactive oxygen species (ROS) form a class of molecules with both positive and negative impacts on cellular health. Negatively, ROS may react with cellular constituents including proteins, lipids, and DNA to generate an array of oxidative lesions. These lesions may compromise genome stability which is critical for long-term cellular homeostasis and healthy progeny. Paradoxically, ROS also function as strong signalling molecules that mediate various growth-related responses, so their presence is also essential for cellular metabolism. While ROS are generated in an unregulated manner by physical stresses such as exposure to ionizing radiation and biochemical malfunctions such as mitochondrial leakage, cells also contain the NADPH oxidases NOXs and DUOXs, which specifically generate ROS in a wide variety of tissues. While the NOXs/DUOXs may be involved in maintaining optimal cellular redox levels, there is also accumulating evidence that NADPH oxidases-derived ROS may elevate the risk for genomic instability and cancer. Cancer cells may produce high levels of ROS, and in some cases, the source of these ROS has been linked to NOX/DUOX deregulation as reported for prostate cancer (NOX1 and NOX5), melanoma and glioblastoma (NOX4) among others. In addition, recent studies reveal that targeting NADPH oxidases with NOXs inhibitors may impair tumor growth in vivo; indicating that these proteins may be useful targets in future clinical strategies to fight cancer. This review provides an overview of the current knowledge concerning these enzymes, their roles in cancer, and their potential as targets in future cancer therapies.
C1 [Weyemi, Urbain; Redon, Christophe E.; Parekh, Palak R.; Bonner, William M.] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
[Dupuy, Corinne] Univ Paris 11, Inst Gustave Roussy, CNRS, UMR 8200, F-94805 Villejuif, France.
RP Weyemi, U (reprint author), NCI, Bldg 37,Room 5050,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM urbain.weyemi@nih.gov
RI Parekh, Palak/B-7042-2015; Weyemi, Urbain/E-2083-2016
OI Parekh, Palak/0000-0001-9201-5194;
FU NIAID Radiation/Nuclear Countermeasures Program; National Cancer
Institute, Center for Cancer Research, NIH
FX We thank Dr. Thomas L. Leto (National Institutes of Health, NIH) for the
critical reading of the manuscript. This research was supported by the
NIAID Radiation/Nuclear Countermeasures Program and the Intramural
Research Program of the National Cancer Institute, Center for Cancer
Research, NIH.
NR 108
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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 1871-5206
J9 ANTI-CANCER AGENT ME
JI Anti-Cancer Agents Med. Chem.
PD MAR
PY 2013
VL 13
IS 3
BP 502
EP 514
PG 13
WC Oncology; Chemistry, Medicinal
SC Oncology; Pharmacology & Pharmacy
GA 129OB
UT WOS:000317849500013
PM 22931418
ER
PT J
AU Garcia-Crespo, KE
Chan, CC
Gabryszewski, SJ
Percopo, CM
Rigaux, P
Dyer, KD
Domachowske, JB
Rosenberg, HF
AF Garcia-Crespo, Katia E.
Chan, Calvin C.
Gabryszewski, Stanislaw J.
Percopo, Caroline M.
Rigaux, Peter
Dyer, Kimberly D.
Domachowske, Joseph B.
Rosenberg, Helene F.
TI Lactobacillus priming of the respiratory tract: Heterologous immunity
and protection against lethal pneumovirus infection
SO ANTIVIRAL RESEARCH
LA English
DT Article
DE Cytokines; Neutrophils; Peptidoglycan; Genomic DNA; Heterologous
immunity
ID INFLUENZA-VIRUS INFECTION; NONTYPABLE HAEMOPHILUS-INFLUENZAE; SYNCYTIAL
VIRUS; BACTERIAL PNEUMONIA; MONOCLONAL-ANTIBODY; VIRAL-INFECTIONS; MICE;
INNATE; NOD2; PEPTIDOGLYCAN
AB We showed previously that wild-type mice primed via intranasal inoculation with live or heat-inactivated Lactobacillus species were fully (100%) protected against the lethal sequelae of infection with the virulent pathogen, pneumonia virus of mice (PVM), a response that is associated with diminished expression of proinflammatory cytokines and diminished virus recovery. We show here that 40% of the mice primed with live Lactobacillus survived when PVM challenge was delayed for 5 months. This robust and sustained resistance to PVM infection resulting from prior interaction with an otherwise unrelated microbe is a profound example of heterologous immunity. We undertook the present study in order to understand the nature and unique features of this response. We found that intranasal inoculation with L. reuteri elicited rapid, transient neutrophil recruitment in association with proinflammatory mediators (CXCL1, CCL3, CCL2, CXCL10, TNF-alpha and IL-17A) but not Th1 cytokines. IFN gamma does not contribute to survival promoted by Lactobacillus-priming. Live L reuteri detected in lung tissue underwent rapid clearance, and was undetectable at 24 h after inoculation. In contrast, L reuteri peptidoglycan (PGN) and L. reuteri genomic DNA (gDNA) were detected at 24 and 48 h after inoculation, respectively. In contrast to live bacteria, intranasal inoculation with isolated L. reuteri gDNA elicited no neutrophil recruitment, had minimal impact on virus recovery and virus-associated production of CCL3, and provided no protection against the negative sequelae of virus infection. Isolated PGN elicited neutrophil recruitment and proinflammatory cytokines but did not promote sustained survival in response to subsequent PVM infection. Overall, further evaluation of the responses leading to. Lactobacillus-mediated heterologous immunity may provide insight into novel antiviral preventive modalities. Published by Elsevier B.V.
C1 [Garcia-Crespo, Katia E.; Chan, Calvin C.; Gabryszewski, Stanislaw J.; Percopo, Caroline M.; Rigaux, Peter; Dyer, Kimberly D.; Rosenberg, Helene F.] NIAID, Inflammat Immunobiol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Domachowske, Joseph B.] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA.
RP Rosenberg, HF (reprint author), NIAID, Inflammat Immunobiol Sect, Lab Allerg Dis, NIH, Bldg 10,Room 11C215,MSC 1883, Bethesda, MD 20892 USA.
EM hrosenberg@niaid.nih.gov
FU NIAID Division of Intramural Research (DIR) [AI000943]; Children's
Miracle Network of New York
FX The authors are grateful for the assistance of Dr. Alfonso Gonzalo and
the staff of National Institute of Allergy and Infectious Diseases 14BS
animal facility for care of mice used in these studies, Mr. Ricardo
Dreyfuss of Medical Arts who prepared the photomicrographs for
publication, and Dr. Stephanie Glineur for performing the studies to
detect serum antibodies to PVM. HFR would also like to thank Dr. Peter
J. Openshaw who brought the concept of innate imprinting to our
attention. This work is funded by NIAID Division of Intramural Research
(DIR) AI000943 to HFR and Children's Miracle Network of New York to JBD.
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U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-3542
J9 ANTIVIR RES
JI Antiviral Res.
PD MAR
PY 2013
VL 97
IS 3
BP 270
EP 279
DI 10.1016/j.antiviral.2012.12.022
PG 10
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA 127OX
UT WOS:000317709400008
PM 23274789
ER
PT J
AU Lu, J
Bian, ZY
Zhang, R
Zhang, Y
Liu, C
Yan, L
Zhang, SM
Jiang, DS
Wei, X
Zhu, XH
Chen, MY
Wang, AB
Chen, YJ
Yang, QL
Liu, PP
Li, HL
AF Lu, Jing
Bian, Zhou-Yan
Zhang, Ran
Zhang, Yan
Liu, Chen
Yan, Ling
Zhang, Shu-Min
Jiang, Ding-Sheng
Wei, Xiang
Zhu, Xue Hai
Chen, Manyin
Wang, Ai-Bing
Chen, Yingjie
Yang, Qinglin
Liu, Peter P.
Li, Hongliang
TI Interferon regulatory factor 3 is a negative regulator of pathological
cardiac hypertrophy
SO BASIC RESEARCH IN CARDIOLOGY
LA English
DT Article
DE IRF3; Hypertrophy; Remodeling; Signal transduction; ERK1/2
ID TRANSCRIPTION FACTORS; HEART-FAILURE; SIGNALING PATHWAYS;
CALCINEURIN-NFAT; PROTEIN-KINASE; IN-VIVO; ACTIVATION; EXPRESSION;
GROWTH; CELLS
AB Interferon regulatory factor (IRF) 3, a member of the highly conserved IRF family transcription factors, plays a pivotal role in innate immune response, apoptosis, and oncogenesis. Recent studies have implicated IRF3 in a wide range of host defense. However, whether IRF3 induces defensive responses to hypertrophic stresses such as biomechanical stress and neurohumoral factors remains unclear. Herein, we employed an IRF3-deficient mouse model, cardiac-specific IRF3-overexpression mouse model and isolated cardiomyocytes to investigate the role of IRF3 in cardiac hypertrophy induced by aortic banding (AB) or isoproterenol (ISO). The extent of cardiac hypertrophy was quantitated by echocardiography as well as by pathological and molecular analysis. Our results demonstrate that IRF3 deficiency profoundly exacerbated cardiac hypertrophy, whereas overexpression of IRF3 in the heart significantly blunted pathological cardiac remodeling induced by pressure overload. Similar results were also observed in cultured cardiomyocytes upon the treatment with ISO. Mechanistically, we discovered that IRF3 interacted with ERK2 and thereby inhibited the ERK1/2 signaling. Furthermore, inactivation of ERK1/2 by U0126 offset the IRF3-deficient-mediated hypertrophic response induced by aortic banding. Altogether, these data demonstrate that IRF3 plays a protective role in AB-induced hypertrophic response by inactivating ERK1/2 in the heart. Therefore, IRF3 could be a new target for the prevention and therapy of cardiac hypertrophy and failure.
C1 [Lu, Jing; Bian, Zhou-Yan; Zhang, Yan; Yan, Ling; Zhang, Shu-Min; Jiang, Ding-Sheng; Li, Hongliang] Wuhan Univ, Cardiovasc Res Inst, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China.
[Zhang, Ran] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100005, Peoples R China.
[Zhang, Ran] Peking Union Med Coll, Beijing 100005, Peoples R China.
[Liu, Chen] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Cardiol, Guangzhou 510275, Guangdong, Peoples R China.
[Wei, Xiang; Zhu, Xue Hai] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Thorac & Cardiovasc Surg, Wuhan 430030, Peoples R China.
[Chen, Manyin; Liu, Peter P.] Univ Toronto, Richard Lewar Ctr Excellence, Div Cardiol Heart & Stroke, Toronto, ON, Canada.
[Wang, Ai-Bing] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Yingjie] Univ Minnesota, Div Cardiovasc, Minneapolis, MN 55455 USA.
[Yang, Qinglin] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
RP Li, HL (reprint author), Wuhan Univ, Cardiovasc Res Inst, Renmin Hosp, Dept Cardiol, Jiefang Rd 238, Wuhan 430060, Peoples R China.
EM lihl@whu.edu.cn
FU Funds for Distinguished Young Scientists of Hubei [2010CDA092]; National
Natural Science Foundation of China [30900524, 81170086, 3087451,
30801351]; National Science and Technology Support Project
[2011BAI15B02, 2012BAI39B05]; National Basic Research Program of China
[2011CB503902]
FX We thank Dr. Tadatsugu Taniguchi for providing IRF3-knockout mice and
Dr. Kensuke Tsushima for discussion by Email. This study was supported
Funds for Distinguished Young Scientists of Hubei (2010CDA092) and by
the National Natural Science Foundation of China (Grants 30900524 and
81170086, 3087451 and 30801351), and National Science and Technology
Support Project (NO. 2011BAI15B02 and No. 2012BAI39B05), National Basic
Research Program of China (No. 2011CB503902).
NR 53
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U1 0
U2 21
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0300-8428
J9 BASIC RES CARDIOL
JI Basic Res. Cardiol.
PD MAR
PY 2013
VL 108
IS 2
AR 326
DI 10.1007/s00395-012-0326-9
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 121JK
UT WOS:000317239300002
PM 23307144
ER
PT J
AU Mamounas, EP
Tang, G
Paik, S
Baehner, FL
Jeong, J
Sing, A
Butler, SM
Sing, AP
Shak, S
Wolmark, N
AF Mamounas, E. P.
Tang, G.
Paik, S.
Baehner, F. L.
Jeong, J.
Sing, A.
Butler, S. M.
Sing, A. P.
Shak, S.
Wolmark, N.
TI RECURRENCE SCORE FOR PROGNOSIS AND PREDICTION OF PACLITAXEL BENEFIT IN
NODE(+)/ER(+) BREAST CANCER
SO BREAST
LA English
DT Meeting Abstract
C1 [Mamounas, E. P.; Jeong, J.; Wolmark, N.] NSABP Operat & Biostat Ctr, Pittsburgh, PA USA.
[Tang, G.; Paik, S.] NSABP, Pittsburgh, PA USA.
[Baehner, F. L.] Genom Hlth Inc, Pathol, Redwood City, CA USA.
[Sing, A.; Sing, A. P.; Shak, S.] Genom Hlth Inc, Pathol, Biostat, Med Affairs, Redwood City, CA USA.
[Butler, S. M.] Genom Hlth Inc, Pathol, Biostat, Redwood City, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0960-9776
J9 BREAST
JI Breast
PD MAR
PY 2013
VL 22
SU 1
BP S89
EP S90
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 126PZ
UT WOS:000317634800234
ER
PT J
AU Estey, MP
Diamandis, EP
Eisenhofer, G
Pacak, K
Maher, ER
Young, WF
de Krijger, RR
AF Estey, Mathew P.
Diamandis, Eleftherios P.
Eisenhofer, Graeme
Pacak, Karel
Maher, Eamonn R.
Young, William F.
de Krijger, Ronald R.
TI Pheochromocytoma
SO CLINICAL CHEMISTRY
LA English
DT Editorial Material
C1 [Estey, Mathew P.; Diamandis, Eleftherios P.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[Diamandis, Eleftherios P.] Univ Hlth Network, Dept Clin Biochem, Toronto, ON, Canada.
[Diamandis, Eleftherios P.] Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5T 3L9, Canada.
[Eisenhofer, Graeme] Tech Univ Dresden, Inst Clin Chem & Lab Med, D-01062 Dresden, Germany.
[Eisenhofer, Graeme] Tech Univ Dresden, Dept Med, Univ Hosp, D-01062 Dresden, Germany.
[Pacak, Karel] Eunice Kennedy Shriver NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Maher, Eamonn R.] Univ Birmingham, Sch Med, Ctr Rare Dis & Personalised Med, Inst Biomed Res West, Birmingham, W Midlands, England.
[Young, William F.] Mayo Clin, Div Endocrinol, Rochester, MN USA.
[de Krijger, Ronald R.] Erasmus MC Univ, Med Ctr Rotterdam, Dept Pathol, Josephine Nefkens Inst, Rotterdam, Netherlands.
RP Diamandis, EP (reprint author), Mt Sinai Hosp, Joseph & Wolf Lebov Ctr, 60 Murray St Box 32,Flr 6,Rm L6-201, Toronto, ON M5T 3L9, Canada.
EM ediamandis@mtsinai.on.ca
RI MAHER, EAMONN/A-9507-2008;
OI MAHER, EAMONN/0000-0002-6226-6918; Diamandis,
Eleftherios/0000-0002-1589-820X
FU Intramural NIH HHS [ZIA HD008735-11, ZIA HD008735-13]
NR 0
TC 8
Z9 8
U1 0
U2 4
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD MAR
PY 2013
VL 59
IS 3
BP 466
EP 472
DI 10.1373/clinchem.2012.182246
PG 7
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 122SE
UT WOS:000317337600004
PM 23209036
ER
PT J
AU Hartman, RL
Huestis, MA
AF Hartman, Rebecca L.
Huestis, Marilyn A.
TI Cannabis Effects on Driving Skills
SO CLINICAL CHEMISTRY
LA English
DT Review
CT Society-of-Forensic-Toxicologists Conference
CY 2012
CL Boston, MA
SP Soc Forens Toxicologists
ID VEHICLE COLLISION RISK; ORAL FLUID; BLOOD CANNABINOIDS; TRAFFIC
INJURIES; MOTOR CONTROL; MARIJUANA USE; ALCOHOL; PERFORMANCE; DRIVERS;
THC
AB BACKGROUND: Cannabis is the most prevalent illicit drug identified in impaired drivers. The effects of cannabis on driving continue to be debated, making prosecution and legislation difficult. Historically, delays in sample collection, evaluating the inactive Delta(9)-tetrahydrocannabinol (THC) metabolite 11-nor-9-carboxy-THC, and polydrug use have complicated epidemiologic evaluations of driver impairment after cannabis use.
CONTENT: We review and evaluate the current literature on cannabis' effects on driving, highlighting the epidemiologic and experimental data. Epidemiologic data show that the risk of involvement in a motor vehicle accident (MVA) increases approximately 2-fold after cannabis smoking. The adjusted risk of driver culpability also increases substantially, particularly with increased blood THC concentrations. Studies that have used urine as the biological matrix have not shown an association between cannabis and crash risk. Experimental data show that drivers attempt to compensate by driving more slowly after smoking cannabis, but control deteriorates with increasing task complexity. Cannabis smoking increases lane weaving and impaired cognitive function. Critical-tracking tests, reaction times, divided-attention tasks, and lane-position variability all show cannabis-induced impairment. Despite purported tolerance in frequent smokers, complex tasks still show impairment. Combining cannabis with alcohol enhances impairment, especially lane weaving.
SUMMARY: Differences in study designs frequently account for inconsistencies in results between studies. Participant-selection bias and confounding factors attenuate ostensible cannabis effects, but the association with MVA often retains significance. Evidence suggests recent smoking and/or blood THC concentrations 2-5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers. Future cannabis-and-driving research should emphasize challenging tasks, such as divided attention, and include occasional and chronic daily cannabis smokers. (C) 2012 American Association for Clinical Chemistry
C1 [Hartman, Rebecca L.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Hartman, Rebecca L.] Univ Maryland, Toxicol Program, Grad Program Life Sci, Baltimore, MD 21201 USA.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200,Rm 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural NIH HHS [ZIA DA000413-12]
NR 74
TC 90
Z9 91
U1 6
U2 70
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
EI 1530-8561
J9 CLIN CHEM
JI Clin. Chem.
PD MAR
PY 2013
VL 59
IS 3
BP 478
EP 492
DI 10.1373/clinchem.2012.194381
PG 15
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 122SE
UT WOS:000317337600008
PM 23220273
ER
PT J
AU Bergamaschi, MM
Karschner, EL
Goodwin, RS
Scheidweiler, KB
Hirvonen, J
Queiroz, RHC
Huestis, MA
AF Bergamaschi, Mateus M.
Karschner, Erin L.
Goodwin, Robert S.
Scheidweiler, Karl B.
Hirvonen, Jussi
Queiroz, Regina H. C.
Huestis, Marilyn A.
TI Impact of Prolonged Cannabinoid Excretion in Chronic Daily Cannabis
Smokers' Blood on Per Se Drugged Driving Laws
SO CLINICAL CHEMISTRY
LA English
DT Article
ID MARIJUANA USE; NEUROPSYCHOLOGICAL PERFORMANCE; GAS-CHROMATOGRAPHY;
MASS-SPECTROMETRY; USERS; HEAVY; THC; DELTA-1-TETRAHYDROCANNABINOL;
PLASMA; BRAIN
AB BACKGROUND: Cannabis is the illicit drug most frequently reported with impaired driving and motor vehicle accidents. Some "per se" laws make it illegal to drive with any amount of drug in the body, while others establish blood, saliva, or urine concentrations above which it is illegal to drive. The persistence of Delta(9)-tetrahydrocannabinol (THC) in chronic daily cannabis smokers' blood is unknown.
METHODS: Thirty male chronic daily cannabis smokers resided on a secure research unit for up to 33 days, with daily blood collection. Samples were processed in an ice bath during sample preparation to minimize cannabinoid adsorption onto precipitant material. We quantified THC by 2-dimensional GC-MS.
RESULTS: Of the 30 participants, 27 were THC-positive on admission, with a median (range) concentration of 1.4 mu g/L (0.3-6.3). THC decreased gradually; only 1 of 11 participants was negative at 26 days, 2 of 5 remained THC-positive (0.3 mu g/L) for 30 days, and 5.0% of participants had THC >= 1.0 mu g/L for 12 days. Median 11-hydroxy-THC concentrations were 1.1 mu g/L on admission, with no results >= 1.0 mu g/L 24 h later. 11-Nor-9-carboxy-THC (THCCOOH) detection rates were 96.7% on admission, decreasing slowly to 95.7% and 85.7% on days 8 and 22, respectively; 4 of 5 participants remained THCCOOH positive (0.6-2.7 mu g/L) after 30 days, and 1 remained positive on discharge at 33 days.
CONCLUSIONS: Cannabinoids can be detected in blood of chronic daily cannabis smokers during a month of sustained abstinence. This is consistent with the time course of persisting neurocognitive impairment reported in recent studies. (C) 2012 American Association for Clinical Chemistry
C1 [Bergamaschi, Mateus M.; Karschner, Erin L.; Goodwin, Robert S.; Scheidweiler, Karl B.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Bergamaschi, Mateus M.; Queiroz, Regina H. C.] Univ Sao Paulo, Sch Pharmaceut Sci, BR-14049 Ribeirao Preto, Brazil.
[Hirvonen, Jussi] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd,Room 05A721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU CAPES (Brazilian Federal Agency for the Support and Evaluation of
Graduate Education); Intramural Research Program, National Institute on
Drug Abuse and National Institute of Mental Health, NIH
FX M.M. Bergamaschi, CAPES (Brazilian Federal Agency for the Support and
Evaluation of Graduate Education); M.A. Huestis, Intramural Research
Program, National Institute on Drug Abuse and National Institute of
Mental Health, NIH.
NR 42
TC 45
Z9 45
U1 3
U2 36
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD MAR
PY 2013
VL 59
IS 3
BP 519
EP 526
DI 10.1373/clinchem.2012.195503
PG 8
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 122SE
UT WOS:000317337600012
PM 23449702
ER
PT J
AU Weymar, M
Bradley, MM
Hamm, AO
Lang, PJ
AF Weymar, Mathias
Bradley, Margaret M.
Hamm, Alfons O.
Lang, Peter J.
TI When fear forms memories: Threat of shock and brain potentials during
encoding and recognition
SO CORTEX
LA English
DT Article
DE Emotion; Memory; Stress; Threat; ERPs
ID EVENT-RELATED POTENTIALS; ANXIETY DISORDERS; ANTICIPATORY ANXIETY;
STRESS; STARTLE; INFORMATION; HUMANS; EMOTION; AROUSAL; REFLEX
AB The anticipation of highly aversive events is associated with measurable defensive activation, and both animal and human research suggests that stress-inducing contexts can facilitate memory. Here, we investigated whether encoding stimuli in the context of anticipating an aversive shock affects recognition memory. Event-related potentials (ERPs) were measured during a recognition test for words that were encoded in a font color that signaled threat or safety. At encoding, cues signaling threat of shock, compared to safety, prompted enhanced P2 and P3 components. Correct recognition of words encoded in the context of threat, compared to safety, was associated with an enhanced old-new ERP difference (500-700 msec; centro-parietal), and this difference was most reliable for emotional words. Moreover, larger old new ERP differences when recognizing emotional words encoded in a threatening context were associated with better recognition, compared to words encoded in safety. Taken together; the data indicate enhanced memory for stimuli encoded in a context in which an aversive event is merely anticipated, which could assist in understanding effects of anxiety and stress on memory processes. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Weymar, Mathias; Bradley, Margaret M.; Lang, Peter J.] Univ Florida, NIMH Ctr Study Emot & Attent, Gainesville, FL 32611 USA.
[Hamm, Alfons O.] Ernst Moritz Arndt Univ Greifswald, Dept Biol & Clin Psychol, Greifswald, Germany.
RP Weymar, M (reprint author), Univ Florida, NIMH Ctr Study Emot & Attent, POB 112766, Gainesville, FL 32611 USA.
EM mweymar@ufl.edu; bradley@ufl.edu; hamm@uni-greifswald.de;
langp@phhp.ufl.edu
FU NIMH [P50-MH072850, MH082702]; German Research Society (Deutsche
Forschungsgemeinschaft, DFG) [WE 4801/1-1]
FX This research was supported in part by NIMH grants P50-MH072850 and
MH082702 to Peter Lang and Margaret Bradley at the University of Florida
Center for the Study of Emotion and Attention and by a post-doctoral
stipend from the German Research Society (Deutsche
Forschungsgemeinschaft, DFG) to Mathias Weymar (Forschungsstipendium, WE
4801/1-1).
NR 47
TC 15
Z9 17
U1 5
U2 25
PU ELSEVIER MASSON
PI MILANO
PA VIA PALEOCAPA 7, 20121 MILANO, ITALY
SN 0010-9452
J9 CORTEX
JI Cortex
PD MAR
PY 2013
VL 49
IS 3
BP 819
EP 826
DI 10.1016/j.cortex.2012.02.012
PG 8
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 122MT
UT WOS:000317322900020
PM 22483973
ER
PT J
AU Pecina, M
Mickey, BJ
Love, T
Wang, H
Langenecker, SA
Hodgkinson, C
Shen, PH
Villafuerte, S
Hsu, D
Weisenbach, SL
Stohler, CS
Goldman, D
Zubieta, JK
AF Pecina, Marta
Mickey, Brian J.
Love, Tiffany
Wang, Heng
Langenecker, Scott A.
Hodgkinson, Colin
Shen, Pei-Hong
Villafuerte, Sandra
Hsu, David
Weisenbach, Sara L.
Stohler, Christian S.
Goldman, David
Zubieta, Jon-Kar
TI DRD2 polymorphisms modulate reward and emotion processing, dopamine
neurotransmission and openness to experience
SO CORTEX
LA English
DT Article
DE Imaging; Dopamine; DLPFC; Reward; Emotion
ID DORSOLATERAL PREFRONTAL CORTEX; TREATMENT-RESISTANT DEPRESSION; DEEP
BRAIN-STIMULATION; VENTRAL TEGMENTAL AREA; RECEPTOR GENE; MAJOR
DEPRESSION; MOOD DISORDERS; SCHIZOPHRENIA; FMRI; ACTIVATION
AB Dopamine (DA) neurotransmission through D2 receptors (DRD2) has been implicated in the regulation of reward processing, cognition and the effects of drugs of abuse, and also has significant effects in responses to stressors and salient aversive stimuli. An examination of the influence of genetic variation across multiple psychophysical measures therefore appears critical to understand the neurobiology of DA-modulated complex personality traits and psychiatric illnesses. To examine inter-individual variation in the function of DRD2 modulated mechanisms in healthy humans, we used a haplotype-based and single nucleotide polymorphism (SNP) investigation. Their effects were interrogated with functional magnetic resonance imaging during reward and emotional processing. We found that a haplotype block composed by two SNPs, rs4274224 and rs4581480, affected the hemodynamic responses of the dorsolateral prefrontal cortex (DLPFC) during reward expectation and the subgenual anterior cingulate cortices (sgACC) during implicit emotional processing. Exploratory analysis within the significant haplotype block revealed the same functional effects only for the SNP rs4274224. Further analysis on rs4274224 using functional connectivity and positron emission tomography (PET) measures of DA D-2/3 receptor mediated neurotransmission confirmed a gene effect on the functional connectivity of the DLPFC during reward anticipation and subcortical stress induced DA release. At a phenotypic trait level, significant effects of genotype were obtained for the NEO PI-R "Openness to Experience" and further correlated with neuroimaging data. Overall, these results show significant neurobiological effects of genotype variation in DRD2 on multiple functional domains, such as emotional, stress and reward processing. As such, it contributes to normal variation and potentially to vulnerability to psychopathology associated with those functions, such as risk for mood and substance use disorders. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Pecina, Marta; Wang, Heng; Villafuerte, Sandra; Zubieta, Jon-Kar] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA.
[Hodgkinson, Colin; Shen, Pei-Hong; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
[Mickey, Brian J.; Love, Tiffany; Langenecker, Scott A.; Villafuerte, Sandra; Hsu, David; Weisenbach, Sara L.; Zubieta, Jon-Kar] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Zubieta, Jon-Kar] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA.
[Stohler, Christian S.] Univ Maryland, Sch Dent, College Pk, MD 20742 USA.
RP Zubieta, JK (reprint author), Univ Michigan, 205 Zina Pitcher Pl, Ann Arbor, MI 48109 USA.
EM zubieta@umich.edu
RI Mickey, Brian/J-1756-2014; Hsu, David/J-5814-2014; Goldman,
David/F-9772-2010; Weisenbach, Sara/M-2384-2016;
OI Mickey, Brian/0000-0002-7847-7680; Goldman, David/0000-0002-1724-5405;
Weisenbach, Sara/0000-0002-5330-4038; Love, Tiffany/0000-0001-9299-3190
FU Phil F. Jenkins Foundation; Alicia Koplowitz Foundation; [R01 DA
016423]; [R01 DA 022520]; [K01 MH 074459]; [K01 MH 085035]
FX Work was supported by R01 DA 016423, R01 DA 022520 (JKZ), a career
development award, K01 MH 074459 (SAL), K01 MH 085035 (DTH), the Phil F.
Jenkins Foundation and the Alicia Koplowitz Foundation. We would also
like to acknowledge the contribution of the technologists of the
functional MRI laboratory and the PET Center at the University of
Michigan.
NR 99
TC 25
Z9 27
U1 2
U2 23
PU ELSEVIER MASSON
PI MILANO
PA VIA PALEOCAPA 7, 20121 MILANO, ITALY
SN 0010-9452
J9 CORTEX
JI Cortex
PD MAR
PY 2013
VL 49
IS 3
BP 877
EP 890
DI 10.1016/j.cortex.2012.01.010
PG 14
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 122MT
UT WOS:000317322900025
PM 22424959
ER
PT J
AU Ma, C
Wang, Y
Zhang, G
Chen, Z
Qiu, Y
Li, J
Luo, J
Huang, B
Jiang, C
Huang, G
Wan, X
Korteweg, C
Gu, J
AF Ma, C.
Wang, Y.
Zhang, G.
Chen, Z.
Qiu, Y.
Li, J.
Luo, J.
Huang, B.
Jiang, C.
Huang, G.
Wan, X.
Korteweg, C.
Gu, J.
TI Immunoglobulin G Expression and its Potential Role in Primary and
Metastatic Breast Cancers
SO CURRENT MOLECULAR MEDICINE
LA English
DT Article
DE Breast cancer; complement; immune escape; immunoglobulin G; metastasis
ID CELL-LINES; GENE TRANSCRIPTS; CA215; ACTIVATION; COMPLEXES; BIOMARKER;
SURVIVAL; RECEPTOR; GROWTH; LUNGS
AB Recently immunoglobulin G (IgG) was found to be produced by neoplasms and promote tumor growth in cancer cell lines and animal models. To investigate the pathophysiological significance of cancer-produced IgG in breast cancer, we examined the expressions of IgG in 68 breast cancers including 40 primary cancers without metastasis and 28 cancers with axillary lymph node metastases. IgG gene expression was detected in all these samples. We found that IgG-expressing cancer cells were predominantly located in the periphery of the primary cancer nest and that these cells showed more cellular atypia and nuclear pleomorphism. We also found that the abundance of IgG-expressing cancer cells was higher and the cells were more evenly distributed in the metastatic cancer cells than that in the primary lesion. These findings suggest that IgG-expressing breast cancer cells have a more aggressive biological behavior than the IgG negative cancer cells and it could be an indicator for progression and metastasis of the disease. Co-localization of IgG and C1q complement was detected in both primary and metastatic lesions implying that immune complexes might be formed in situ. We speculate that such immune complexes might facilitate immune escape of cancer cells. Our findings suggest that locally produced IgG plays important roles in breast cancer, and may serve as a potential therapeutic target.
C1 [Ma, C.; Wang, Y.; Chen, Z.; Qiu, Y.; Li, J.; Luo, J.; Huang, B.; Jiang, C.; Huang, G.; Wan, X.; Korteweg, C.; Gu, J.] Shantou Univ, Coll Med, Guangdong Prov Key Lab Infect Dis & Mol Immunopat, Dept Pathol & Pathophysiol, Shantou 515041, Guangdong, Peoples R China.
[Ma, C.] Shantou Univ, Coll Med, Canc Hosp, Dept Radiat Oncol, Shantou 515041, Guangdong, Peoples R China.
[Wang, Y.] NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA.
[Zhang, G.] Shantou Univ, Coll Med, Breast Ctr, Canc Hosp, Shantou 515041, Guangdong, Peoples R China.
[Gu, J.] Beijing Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100871, Peoples R China.
RP Gu, J (reprint author), Shantou Univ, Coll Med, Guangdong Prov Key Lab Infect Dis & Mol Immunopat, 22 Xinling Rd, Shantou 515041, Guangdong, Peoples R China.
EM jguemailbox@gmail.com
RI Chen, Zhengshan/J-7499-2014; Zhang, Guo-Jun/H-3890-2015
OI Zhang, Guo-Jun/0000-0001-5182-5887
FU National Nature Science Foundation of China [81030033, 30971150,
81001199, 30950110335]; Natural Science Foundation of Guangdong Province
[8451503102001823]; Guangdong Provincial Key Laboratory; Science and
Technology Foundation of Shantou [186]; Breast Center in Cancer Hospital
of Shantou University Medical College
FX This work was supported by grants from the National Nature Science
Foundation of China (No. 81030033, 30971150 to J.G., No. 81001199 to
Z.C. and No. 30950110335 to C. K.), the Natural Science Foundation of
Guangdong Province (No. 8451503102001823), the Guangdong Provincial Key
Laboratory, and the Science and Technology Foundation of Shantou (No.
186 to C. M.) and by the Breast Center in Cancer Hospital of Shantou
University Medical College. We also gratefully acknowledge Prof. Min Su
and his colleagues (Department of Pathology, Shantou University Medical
College) for their help in providing tissue samples.
NR 29
TC 11
Z9 14
U1 2
U2 14
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1566-5240
J9 CURR MOL MED
JI Curr. Mol. Med.
PD MAR
PY 2013
VL 13
IS 3
BP 429
EP 437
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 119RV
UT WOS:000317116100012
PM 23331015
ER
PT J
AU Wu, DC
Zhuang, DM
Liu, XF
Lu, LH
Wang, H
Li, C
Lai, CC
Li, JY
He, YP
AF Wu, Dao-Chun
Zhuang, Dao-Ming
Liu, Xiao-Feng
Lu, Li-He
Wang, Hua
Li, Cong
Lai, Christopher Cong
Li, Jing-Yun
He, Yan-Ping
TI Synthesis and Biological Evaluation of Novel Hydroxylphenethyl-S-DACOs
as High Active Anti-HIV Agents
SO LETTERS IN DRUG DESIGN & DISCOVERY
LA English
DT Article
DE Anti HIV-1 activity; Water-solubility; Molecular Docking; NNRTIs;
Pyrimidone; S-DACOs
ID REVERSE-TRANSCRIPTASE INHIBITORS; DABO SERIES; PYRIMIDIN-4(3H)-ONES;
DERIVATIVES; NNRTIS
AB A novel 5-alky-6-(cyclohexylmethyl)-2-((2-hydroxy-2-phenylethyl)thio)-pyrimidin-4(3H)-one derivatives were synthesized and their ability to inhibit HIV evaluated. The screening results revealed that compounds 2a-g had a favorable property in inhibiting HIV. The compounds 2b, in particular, showed a special potent anti-HIV activities with EC50 values of 0.003 mu M and CC50 values of 200 mu M. Preliminary structure-activity relationship (SAR) and molecular modeling analyses of these newly synthesized hydroxylphenethyl-S-DACOs are also discussed.
C1 [Wu, Dao-Chun; Liu, Xiao-Feng; Lu, Li-He; Wang, Hua; Li, Cong; He, Yan-Ping] Yunnan Univ, Key Lab Med Chem Nat Resources, Minist Educ, Sch Chem Sci & Technol, Kunming 650091, Peoples R China.
[Zhuang, Dao-Ming; Li, Jing-Yun] Acad Mil Med Sci, Inst Microbiol & Epidemiol, Beijing 100071, Peoples R China.
[Lai, Christopher Cong] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Li, JY (reprint author), Yunnan Univ, Key Lab Med Chem Nat Resources, Minist Educ, Sch Chem Sci & Technol, Kunming 650091, Peoples R China.
EM lijy@nic.bmi.an.cn; yphe@ynu.edu.cn
FU National Natural Science-Foundation of China [30560179, 30960459];
Science Foundation of Chinese academy science [W8090303]; Science
Foundation of Yunnan province [2010CI019]
FX Financial support from the National Natural Science-Foundation of China
(Grant No. 30560179 and 30960459), the Science Foundation of Chinese
academy science (Grant No.W8090303) and the Science Foundation of Yunnan
province (Grant No. 2010CI019) are gratefully acknowledged.
NR 14
TC 2
Z9 2
U1 0
U2 5
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1570-1808
J9 LETT DRUG DES DISCOV
JI Lett. Drug Des. Discov.
PD MAR
PY 2013
VL 10
IS 3
BP 271
EP 276
PG 6
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 130NW
UT WOS:000317926100010
ER
PT J
AU Domingos-Pereira, S
Decrausaz, L
Derre, L
Bobst, M
Romero, P
Schiller, JT
Jichlinski, P
Nardelli-Haefliger, D
AF Domingos-Pereira, S.
Decrausaz, L.
Derre, L.
Bobst, M.
Romero, P.
Schiller, J. T.
Jichlinski, P.
Nardelli-Haefliger, D.
TI Intravaginal TLR agonists increase local vaccine-specific CD8 T cells
and human papillomavirus-associated genital-tumor regression in mice
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID SIMPLEX-VIRUS TYPE-2; CERVICAL-CANCER; BACTERIAL-DNA; CPG; RESPONSES;
MUCOSA; OLIGODEOXYNUCLEOTIDES; IMMUNOTHERAPY; EXPRESSION; INDUCTION
AB Human ppillomaviruses (HPV)-related cervical cancer is the second leading cause of cancer death in women worldwide. Despite active development, HPV E6/E7 oncogene-specific therapeutic vaccines have had limited clinical efficacy to date. Here, we report that intravaginal (IVAG) instillation of CpG-ODN (TLR9 agonist) or poly-(I:C) (TLR3 agonist) after subcutaneous E7 vaccination increased similar to fivefold the number of vaccine-specific interferon-gamma-secreting CD8 T cells in the genital mucosa (GM) of mice, without affecting the E7-specific systemic response. The IVAG treatment locally increased both E7-specific and total CD8 T cells, but not CD4 T cells. This previously unreported selective recruitment of CD8 T cells from the periphery by IVAG CpG-ODN or poly-(I:C) was mediated by TLR9 and TLR3/ melanoma differentiation-associated gene 5 signaling pathways, respectively. For CpG, this recruitment was associated with a higher proportion of GM-localized CD8 T cells expressing both CCR5 and CXCR3 chemokine receptors and E-selectin ligands. Most interestingly, IVAG CpG-ODN following vaccination led to complete regression of large genital HPV tumors in 75% of mice, instead of 20% with vaccination alone. These findings suggest that mucosal application of immunostimulatory molecules might substantially increase the effectiveness of parenterally administered vaccines.
C1 [Domingos-Pereira, S.; Decrausaz, L.; Derre, L.; Bobst, M.; Jichlinski, P.; Nardelli-Haefliger, D.] CHU Vaudois, Dept Urol, CH-1011 Lausanne, Switzerland.
[Domingos-Pereira, S.; Decrausaz, L.; Derre, L.; Bobst, M.; Jichlinski, P.; Nardelli-Haefliger, D.] Univ Lausanne, Lausanne, Switzerland.
[Romero, P.] Univ Lausanne, Ludwig Ctr Canc Res, Lausanne, Switzerland.
[Schiller, J. T.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
RP Nardelli-Haefliger, D (reprint author), CHU Vaudois, Dept Urol, CH-1011 Lausanne, Switzerland.
EM dnardell@hospvd.ch
OI nardelli-haefliger, denise/0000-0003-1812-9905
FU Oncosuisse [OCS 02304-082008]; Swiss National Science Foundation
[310000-112406, 31003A-135109]; Fondation Emma Muschamp
FX This work was supported by Oncosuisse (OCS 02304-082008), the Swiss
National Science Foundation (#310000-112406 and 31003A-135109), and the
Fondation Emma Muschamp. We thank Dr Roland Sahli for his help in
handling the array data and Virginie Martin for her technical help.
NR 49
TC 24
Z9 24
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD MAR
PY 2013
VL 6
IS 2
BP 393
EP 404
DI 10.1038/mi.2012.83
PG 12
WC Immunology
SC Immunology
GA 127TJ
UT WOS:000317721400017
PM 22968420
ER
PT J
AU Kim, H
Gordon, S
Dionne, R
AF Kim, H.
Gordon, S.
Dionne, R.
TI Genome-wide approaches (GWA) in oral and craniofacial diseases research
SO ORAL DISEASES
LA English
DT Review
DE genome-wide; genomics; craniofacial; microarray
ID SQUAMOUS-CELL CARCINOMA; NONSYNDROMIC CLEFT-LIP; DIFFERENTIAL
GENE-EXPRESSION; SUBGINGIVAL MICROBIAL PROFILES;
SYSTEMIC-LUPUS-ERYTHEMATOSUS; CASE-PARENT TRIOS; SALIVARY-GLAND;
SJOGRENS-SYNDROME; CHRONIC PERIODONTITIS; SUSCEPTIBILITY LOCUS
AB Underlying molecular genetic mechanisms of diseases can be deciphered with unbiased strategies using recently developed technologies enabling genome-wide scale investigations. These technologies have been applied in scanning for genetic variations, gene expression profiles, and epigenetic changes for oral and craniofacial diseases. However, these approaches as applied to oral and craniofacial conditions are in the initial stages, and challenges remain to be overcome, including analysis of high throughput data and their interpretation. Here, we review methodology and studies using genome-wide approaches in oral and craniofacial diseases and suggest future directions. Oral Diseases (2013) 19, 111-120
C1 [Kim, H.; Dionne, R.] NINR, NIH, Bethesda, MD 20892 USA.
[Gordon, S.] Univ Maryland, Sch Dent, Baltimore, MD 21201 USA.
RP Dionne, R (reprint author), NINR, NIH, 3 Mem Dr B3 Rm5E28, Bethesda, MD 20892 USA.
EM dionner@mail.nih.gov
FU Intramural NIH HHS [ZIA NR000015-07]
NR 103
TC 0
Z9 0
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1354-523X
J9 ORAL DIS
JI Oral Dis.
PD MAR
PY 2013
VL 19
IS 2
BP 111
EP 120
DI 10.1111/j.1601-0825.2012.01962.x
PG 10
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 124TG
UT WOS:000317489000001
PM 22913301
ER
PT J
AU Bornholdt, R
Helgen, K
Koepfli, KP
Oliveira, L
Lucherini, M
Eizirik, E
AF Bornholdt, Renata
Helgen, Kristofer
Koepfli, Klaus-Peter
Oliveira, Larissa
Lucherini, Mauro
Eizirik, Eduardo
TI Taxonomic revision of the genus Galictis (Carnivora: Mustelidae):
species delimitation, morphological diagnosis, and refined mapping of
geographical distribution
SO ZOOLOGICAL JOURNAL OF THE LINNEAN SOCIETY
LA English
DT Review
DE America; greater grison; lesser grison; morphometrics; Neotropical
region; phylogeny; skin variation; skull variation; taxonomy
ID CHARACTER DISPLACEMENT; BIOGEOGRAPHIC HISTORY; SEXUAL-DIMORPHISM;
AMERICAN MINK; SYSTEMATICS; DIVERSITY; EVOLUTIONARY; PROCYONIDAE;
RADIATION; MAMMALS
AB Although critical for enabling in-depth evolutionary, ecological, or conservation-orientated studies, taxonomic knowledge is still scarce for many groups of organisms, including mammals of the order Carnivora. For some of these taxa, even basic aspects such as species limits and geographical distribution are still uncertain. This is the case for the Neotropical mustelid genus Galictis, considered one of the least studied carnivoran genera in the Americas. To address this issue, we performed a comprehensive assessment of morphological and molecular characters to test the number of species within Galictis, and to characterize their distinctiveness and evolutionary history. In addition, we reviewed and consolidated the available information on the taxonomy of this genus, so as to provide a historical framework upon which we could interpret our data. Our analyses demonstrated that two Galictis species can be clearly delimited and diagnosed using metric and nonmetric morphological characters as well as DNA sequences from mitochondrial and nuclear gene segments. On the basis of this clarified species-level delimitation, we reassessed the geographical range of each Galictis taxon, identifying possible areas of sympatry between them. These results provide a solid taxonomic framework for Galictis, enabling the development of additional studies focusing on this poorly known taxon. (c) 2013 The Linnean Society of London, Zoological Journal of the Linnean Society, 2013, 167, 449-472. doi: 10.1111/j.1096-3642.2012.00859.x
C1 [Bornholdt, Renata; Eizirik, Eduardo] Fac Biociencias PUCRS, BR-90619900 Porto Alegre, RS, Brazil.
[Helgen, Kristofer] Natl Museum Nat Hist, Smithsonian Inst, Div Mammals, Washington, DC 20560 USA.
[Koepfli, Klaus-Peter] NIH, Lab Genom Divers, Frederick, MD 21702 USA.
[Lucherini, Mauro] Univ Nacl Sur, Dept Biol Bioquim & Farm, Grp Ecol Comportamental Mamiferos, RA-8000 Bahia Blanca, Buenos Aires, Argentina.
[Eizirik, Eduardo] Inst Procarnivoros, BR-12945010 Atibaia, SP, Brazil.
RP Eizirik, E (reprint author), Fac Biociencias PUCRS, Av Ipiranga,6681 Predio 12, BR-90619900 Porto Alegre, RS, Brazil.
EM eduardo.eizirik@pucrs.br
RI Eizirik, Eduardo/K-8034-2012
OI Eizirik, Eduardo/0000-0002-9658-0999
FU Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS, Brazil);
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES,
Brazil); Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul
(FAPERGS, Brazil); Smithsonian Institution (USA)
FX The authors wish to thank the people in charge of the mammalian
collections analysed in this study, who made this research project
possible: Carla S. Fontana (MCT-PUCRS), Marcia A. Jardim (FZB/RS),
Felipe Peters (ULBRA), Mauricio Graipel (LAMAq-UFSC), Mario de Vivo
(MZUSP), Joao A. Oliveira (MNHN), Diego A. de Moraes (UFPE), Joao
Alberto de Queiroz (MPEG), Enrique Gonzalez (MNHNA), David Flores
(MACN), Hugo Lopez (MLP), Linda Gordon (USNM), Eileen Westwig (AMNH),
Ned Gilmore (ANSP), Catherine Weisel (MCZ), Bill Stanley and Tracy
Damitz (FMNH), Kristof Zyskowski (YPM), Robert Timm (NHMKU), Chris
Conroy (MVZ), Mark Hafner (LSUMNS), Louise Tomsett and Paula Jenkins
(BMNH), and Clara Stefen (SMT). We also gratefully acknowledge Cladinara
Sarturi and Priscilla Mena Zamberlan (PUCRS, Brazil), as well as Jessica
Tomlin and Hannah Zinnert (both supported through the Werner H. Kirsten
Student Intern Program at the NCI, Frederick, Maryland, USA) for
excellent laboratory assistance. We also thank all members from the
Grupo de Ecologia Comportamental de Mamiferos (GECM) who participated in
sample collection in Argentina, especially Estela Luengos Vidal, Diego
Castillo, Claudia Manfredi, and Emma B. Casanave. Finally, we are
especially grateful to Cristine S. Trinca, Andrea T. Thomaz, Joao Feliz,
Henrique V. Figueiro, Lucas G. da Silva, and Tiago F. da Silva for
support at various stages of this research. This project was supported
by the Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS,
Brazil), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior
(CAPES, Brazil), Fundacao de Amparo a Pesquisa do Estado do Rio Grande
do Sul (FAPERGS, Brazil), and the Smithsonian Institution (USA).
NR 101
TC 7
Z9 12
U1 2
U2 39
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0024-4082
J9 ZOOL J LINN SOC-LOND
JI Zool. J. Linn. Soc.
PD MAR
PY 2013
VL 167
IS 3
BP 449
EP 472
DI 10.1111/j.1096-3642.2012.00859.x
PG 24
WC Zoology
SC Zoology
GA 114NX
UT WOS:000316749600005
ER
PT J
AU Boxer, AL
Gold, M
Huey, E
Gao, FB
Burton, EA
Chow, T
Kao, A
Leavitt, BR
Lamb, B
Grether, M
Knopman, D
Cairns, NJ
Mackenzie, IR
Mitic, L
Roberson, ED
Van Kammen, D
Cantillon, M
Zahs, K
Salloway, S
Morris, J
Tong, G
Feldman, H
Fillitt, H
Dickinson, S
Khachaturian, Z
Sutherland, M
Farese, R
Miller, BL
Cummings, J
AF Boxer, Adam L.
Gold, Michael
Huey, Edward
Gao, Fen-Biao
Burton, Edward A.
Chow, Tiffany
Kao, Aimee
Leavitt, Blair R.
Lamb, Bruce
Grether, Megan
Knopman, David
Cairns, Nigel J.
Mackenzie, Ian R.
Mitic, Laura
Roberson, Erik D.
Van Kammen, Daniel
Cantillon, Marc
Zahs, Kathleen
Salloway, Stephen
Morris, John
Tong, Gary
Feldman, Howard
Fillitt, Howard
Dickinson, Susan
Khachaturian, Zaven
Sutherland, Margaret
Farese, Robert
Miller, Bruce L.
Cummings, Jeffrey
TI Frontotemporal degeneration, the next therapeutic frontier: Molecules
and animal models for frontotemporal degeneration drug development
SO ALZHEIMERS & DEMENTIA
LA English
DT Review
DE Frontotemporal degeneration; Treatment; Tau; Progranulin; TDP-43
ID AMYOTROPHIC-LATERAL-SCLEROSIS; CAENORHABDITIS-ELEGANS MODEL; TRANSGENIC
ZEBRAFISH MODEL; HUMAN SOMATIC-CELLS; MOUSE MODEL; LOBAR DEGENERATION;
ALZHEIMERS-DISEASE; IN-VIVO; NEURODEGENERATIVE DISEASES; PATHOLOGICAL
PHENOTYPES
AB Frontotemporal degeneration (FTD) is a common cause of dementia for which there are currently no approved therapies. Over the past decade, there has been an explosion of knowledge about the biology and clinical features of FTD that has identified a number of promising therapeutic targets as well as animal models in which to develop drugs. The close association of some forms of FTD with neuropathological accumulation of tau protein or increased neuroinflammation due to progranulin protein deficiency suggests that a drug's success in treating FTD may predict efficacy in more common diseases such as Alzheimer's disease. A variety of regulatory incentives, clinical features of FTD such as rapid disease progression, and relatively pure molecular pathology suggest that there are advantages to developing drugs for FTD as compared with other more common neurodegenerative diseases such as Alzheimer's disease. In March 2011, the Frontotemporal Degeneration Treatment Study Group sponsored a conference entitled "FTD, the Next Therapeutic Frontier," which focused on preclinical aspects of FTD drug development. The goal of the meeting was to promote collaborations between academic researchers and biotechnology and pharmaceutical researchers to accelerate the development of new treatments for FTD. Here we report the key findings from the conference, including the rationale for FTD drug development; epidemiological, genetic, and neuropathological features of FTD; FTD animal models and how best to use them; and examples of successful drug development collaborations in other neurodegenerative diseases. (c) 2013 The Alzheimer's Association. All rights reserved.
C1 [Boxer, Adam L.; Kao, Aimee; Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA.
[Gold, Michael] Allon Therapeut, Vancouver, BC, Canada.
[Huey, Edward] Columbia Univ, Dept Neurol, Taub Inst, New York, NY USA.
[Gao, Fen-Biao] Univ Massachusetts, Dept Neurol, Worcester, MA 01605 USA.
[Burton, Edward A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.
[Chow, Tiffany] Univ Toronto, Rotman Res Inst, Toronto, ON, Canada.
[Leavitt, Blair R.] Univ British Columbia, Dept Med, Div Neurol, Ctr Mol Med & Therapeut, Vancouver, BC, Canada.
[Lamb, Bruce] Cleveland Clin Fdn, Lerner Res Inst, Dept Neurosci, Cleveland, OH 44195 USA.
[Grether, Megan; Mitic, Laura] Bluefield Project Cure Frontotemporal Dementia, San Francisco, CA USA.
[Knopman, David] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Cairns, Nigel J.; Morris, John] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Mackenzie, Ian R.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
[Roberson, Erik D.] Univ Alabama Birmingham, Dept Neurol, Sch Med, Birmingham, AL 35294 USA.
[Van Kammen, Daniel] CNS Drug Dev Consultant, Princeton, NJ USA.
[Cantillon, Marc] Crit Path Inst, Rockville, MD USA.
[Zahs, Kathleen] Univ Minnesota, Sch Med, Grossman Ctr Memory Res & Care, Minneapolis, MN 55455 USA.
[Salloway, Stephen] Brown Univ, Sch Med, Dept Neurol, Providence, RI 02912 USA.
[Tong, Gary] Bristol Myers Squibb Co, Princeton, NJ USA.
[Feldman, Howard] Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC V6T 1W5, Canada.
[Fillitt, Howard] Alzheimers Drug Discovery Fdn, New York, NY USA.
[Dickinson, Susan] Assoc Frontotemporal Degenerat, Radnor, PA USA.
[Khachaturian, Zaven] KRA Associates, Potomac, MD USA.
[Sutherland, Margaret] NINDS, NIH, Bethesda, MD 20892 USA.
[Farese, Robert] Gladstone Inst Cardiovasc Dis, San Francisco, CA USA.
[Cummings, Jeffrey] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Las Vegas, NV USA.
RP Boxer, AL (reprint author), Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA.
EM aboxer@memory.ucsf.edu
OI Roberson, Erik/0000-0002-1810-9763; Feldman, Howard/0000-0002-9258-4538;
Burton, Edward/0000-0002-8072-4636
NR 74
TC 25
Z9 25
U1 0
U2 17
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD MAR
PY 2013
VL 9
IS 2
BP 176
EP 188
DI 10.1016/j.jalz.2012.03.002
PG 13
WC Clinical Neurology
SC Neurosciences & Neurology
GA 119JD
UT WOS:000317092700010
PM 23043900
ER
PT J
AU Adam, L
Gold, M
Huey, E
Hu, WT
Rosen, H
Kramer, J
Gao, FB
Burton, EA
Chow, T
Kao, A
Leavitt, BR
Lamb, B
Grether, M
Knopman, D
Cairns, NJ
Mackenzie, IR
Mitic, L
Roberson, ED
Van Kammen, D
Cantillon, M
Zahs, K
Jackson, G
Salloway, S
Morris, J
Tong, G
Feldman, H
Fillit, H
Dickinson, S
Khachaturian, ZS
Sutherland, M
Abushakra, S
Lewcock, J
Farese, R
Kenet, RO
LaFerla, F
Perrin, S
Whitaker, S
Honig, L
Mesulam, MM
Boeve, B
Grossman, M
Miller, BL
Cummings, JL
AF Boxer, Adam L.
Gold, Michael
Huey, Edward
Hu, William T.
Rosen, Howard
Kramer, Joel
Gao, Fen-Biao
Burton, Edward A.
Chow, Tiffany
Kao, Aimee
Leavitt, Blair R.
Lamb, Bruce
Grether, Megan
Knopman, David
Cairns, Nigel J.
Mackenzie, Ian R.
Mitic, Laura
Roberson, Erik D.
Van Kammen, Daniel
Cantillon, Marc
Zahs, Kathleen
Jackson, George
Salloway, Stephen
Morris, John
Tong, Gary
Feldman, Howard
Fillit, Howard
Dickinson, Susan
Khachaturian, Zaven S.
Sutherland, Margaret
Abushakra, Susan
Lewcock, Joseph
Farese, Robert
Kenet, Robert O.
LaFerla, Frank
Perrin, Steve
Whitaker, Steve
Honig, Lawrence
Mesulam, Marsel M.
Boeve, Brad
Grossman, Murray
Miller, Bruce L.
Cummings, Jeffrey L.
TI The advantages of frontotemporal degeneration drug development (part 2
of frontotemporal degeneration: The next therapeutic frontier)
SO ALZHEIMERS & DEMENTIA
LA English
DT Review
DE Frontotemporal degeneration; FTD; Alzheimer's disease; AD; Progressive
supranuclear palsy; Corticobasal degeneration; Treatment; Clinical
trial; Biomarker; Drug development
ID PROGRESSIVE SUPRANUCLEAR PALSY; ADDENBROOKES COGNITIVE EXAMINATION;
RICHARDSON-OLSZEWSKI-SYNDROME; PLACEBO-CONTROLLED TRIAL; LOBAR
DEGENERATION; ALZHEIMERS-DISEASE; DIAGNOSTIC-CRITERIA; BEHAVIORAL
VARIANT; TEST BATTERY; DEMENTIA
AB Frontotemporal degeneration (FTD) encompasses a spectrum of related neurodegenerative disorders with behavioral, language, and motor phenotypes for which there are currently no effective therapies. This is the second of two articles that summarize the presentations and discussions that occurred at two symposia in 2011 sponsored by the Frontotemporal Degeneration Treatment Study Group, a collaborative group of academic and industry researchers that is devoted to developing treatments for FTD. This article discusses the current status of FTD clinical research that is relevant to the conduct of clinical trials, and why FTD research may be an attractive pathway for developing therapies for neurodegenerative disorders. The clinical and molecular features of FTD, including rapid disease progression and relatively pure molecular pathology, suggest that there are advantages to developing drugs for FTD as compared with other dementias. FTD qualifies as orphan indication, providing additional advantages for drug development. Two recent sets of consensus diagnostic criteria will facilitate the identification of patients with FTD, and a variety of neuropsychological, functional, and behavioral scales have been shown to be sensitive to disease progression. Moreover, quantitative neuroimaging measurements demonstrate progressive brain atrophy in FTD at rates that may surpass Alzheimer's disease. Finally, the similarities between FTD and other neurodegenerative diseases with drug development efforts already underway suggest that FTD researchers will be able to draw on this experience to create a road map for FTD drug development. We conclude that FTD research has reached sufficient maturity to pursue clinical development of specific FTD therapies. (C) 2013 The Alzheimer's Association. All rights reserved.
C1 [Boxer, Adam L.; Rosen, Howard; Kramer, Joel; Kao, Aimee; Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA.
[Gold, Michael] Allon Therapeut, Vancouver, BC, Canada.
[Huey, Edward; Honig, Lawrence] Columbia Univ, Dept Neurol, Taub Inst, New York, NY USA.
[Hu, William T.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA.
[Gao, Fen-Biao] Univ Massachusetts, Dept Neurol, Worcester, MA 01605 USA.
[Burton, Edward A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.
[Chow, Tiffany] Univ Toronto, Rotman Res Inst, Toronto, ON, Canada.
[Leavitt, Blair R.] Univ British Columbia, Dept Med, Div Neurol, Ctr Mol Med & Therapeut, Vancouver, BC V6T 1W5, Canada.
[Lamb, Bruce] Cleveland Clin Fdn, Lerner Res Inst, Dept Neurosci, Cleveland, OH 44195 USA.
[Grether, Megan; Mitic, Laura] Bluefield Project Cure Frontotemporal Dementia, San Francisco, CA USA.
[Knopman, David; Boeve, Brad] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Cairns, Nigel J.; Morris, John] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Mackenzie, Ian R.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
[Roberson, Erik D.] Univ Alabama Birmingham, Dept Neurol, Sch Med, Birmingham, AL 35294 USA.
[Van Kammen, Daniel] CNS Drug Dev Consultant, Princeton, NJ USA.
[Cantillon, Marc] Crit Path Inst, Rockville, MD USA.
[Zahs, Kathleen] Univ Minnesota, Sch Med, Grossman Ctr Memory Res & Care, Minneapolis, MN 55455 USA.
[Cantillon, Marc] Univ Texas Med Branch, Dept Neurol, Galveston, TX 77555 USA.
[Chow, Tiffany] Brown Univ, Sch Med, Dept Neurol, Providence, RI 02912 USA.
[Tong, Gary] Bristol Myers Squibb Co, Princeton, NJ USA.
[Feldman, Howard] Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC V6T 1W5, Canada.
[Fillit, Howard] Alzheimers Drug Discovery Fdn, New York, NY USA.
[Dickinson, Susan] Assoc Frontotemporal Degenerat, Radnor, PA USA.
[Khachaturian, Zaven S.] KRA Associates, Potomac, MD USA.
[Sutherland, Margaret] NINDS, NIH, Bethesda, MD 20892 USA.
[Abushakra, Susan] Elan Pharmaceut, San Francisco, CA USA.
[Lewcock, Joseph] Genentech Inc, San Francisco, CA 94080 USA.
[Farese, Robert] Gladstone Inst Cardiovasc Dis, San Francisco, CA USA.
[Kenet, Robert O.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[LaFerla, Frank] Univ Calif Irvine, MIND Inst, Irvine, CA USA.
[Perrin, Steve] ALS Therapy Dev Inst, Cambridge, MA USA.
[Whitaker, Steve] Omeros Corp, Seattle, WA USA.
[Mesulam, Marsel M.] Northwestern Univ, Feinberg Sch Med, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL 60611 USA.
[Grossman, Murray] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[Cummings, Jeffrey L.] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Las Vegas, NV USA.
RP Boxer, AL (reprint author), Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA.
EM aboxer@memory.ucsf.edu
OI Roberson, Erik/0000-0002-1810-9763; Feldman, Howard/0000-0002-9258-4538;
Burton, Edward/0000-0002-8072-4636
NR 67
TC 0
Z9 0
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD MAR
PY 2013
VL 9
IS 2
BP 189
EP 198
DI 10.1016/j.jalz.2012.03.003
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA 119JD
UT WOS:000317092700011
ER
PT J
AU Sabatinelli, D
Keil, A
Frank, DW
Lang, PJ
AF Sabatinelli, Dean
Keil, Andreas
Frank, David W.
Lang, Peter J.
TI Emotional perception: Correspondence of early and late event-related
potentials with cortical and subcortical functional MRI
SO BIOLOGICAL PSYCHOLOGY
LA English
DT Article
DE Emotion; Attention; Perception; fMRI; ERP
ID VISUAL-CORTEX; HUMAN AMYGDALA; MOTIVATIONAL RELEVANCE; FACIAL
EXPRESSIONS; BRAIN POTENTIALS; SOCIAL ANXIETY; EEG-FMRI; ATTENTION;
PICTURES; AROUSAL
AB This research examines the relationship between brain activity recorded with functional magnetic resonance imaging (fMRI) and event related potentials (ERP) as these responses varied over a series of emotionally evocative and neutral pictures. We investigate the relationship of early occipitotemporal and later centroparietal emotion-modulated ERPs in one sample to fMRI estimates of neural activity in another sample in a replicated experiment. Using this approach, we aimed to link effects found in time-resolved electrocortical measures to specific neural structures across individual emotional and nonemotional picture stimuli. The centroparietal late positive potential (LPP) showed covariation with emotion-modulated regions of hemodynamic activation across multiple dorsal and ventral visual cortical structures, while the early occipitotemporal potential was not reliably associated. Subcortical and corticolimbic structures involved in the perception of motivationally relevant stimuli also related to modulation of the LPP, and were modestly associated to the amplitude of the early occipitotemporal potential. These data suggest that early occipitotemporal potentials may reflect multiple sources of modulation including motivational relevance, and supports the perspective that the slow-wave LPP represents aggregate cortical and subcortical structures involved in emotional discrimination. (c) 2012 Elsevier B.V. All rights reserved.
C1 [Sabatinelli, Dean; Frank, David W.] Univ Georgia, Dept Psychol, Athens, GA 30601 USA.
[Sabatinelli, Dean; Frank, David W.] Univ Georgia, Bioimaging Res Ctr, Athens, GA 30601 USA.
[Keil, Andreas; Lang, Peter J.] Univ Florida, NIMH Ctr, Study Emot & Attent, Gainesville, FL 32601 USA.
RP Sabatinelli, D (reprint author), Univ Georgia, 523 Psychology Bldg, Athens, GA 30601 USA.
EM sabat@uga.edu
RI Keil, Andreas/F-9427-2011;
OI Keil, Andreas/0000-0002-4064-1924; sabatinelli, dean/0000-0001-7409-8504
FU NIMH NIH HHS [R01 MH084932, P50 MH072850]
NR 60
TC 56
Z9 56
U1 3
U2 33
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0301-0511
J9 BIOL PSYCHOL
JI Biol. Psychol.
PD MAR
PY 2013
VL 92
IS 3
SI SI
BP 513
EP 519
DI 10.1016/j.biopsycho.2012.04.005
PG 7
WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology,
Experimental
SC Psychology; Behavioral Sciences
GA 120JI
UT WOS:000317166200009
PM 22560889
ER
PT J
AU Sinha, BK
Bhattacharjee, S
Chatterjee, S
Jiang, JJ
Motten, AG
Kumar, A
Espey, MG
Mason, RP
AF Sinha, Birandra K.
Bhattacharjee, Suchandra
Chatterjee, Saurabh
Jiang, JinJie
Motten, Ann G.
Kumar, Ashutosh
Espey, Michael Graham
Mason, Ronald P.
TI Role of Nitric Oxide in the Chemistry and Anticancer Activity of
Etoposide (VP-16,213)
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article
ID PROSTATE-CANCER CELLS; BREAST-CANCER; DNA-DAMAGE; RIBONUCLEOTIDE
REDUCTASE; CATALYZED METABOLISM; SYNTHASE EXPRESSION; RADICAL FORMATION;
ALPHA-TOCOPHEROL; NITROGEN-OXIDES; O-DEMETHYLATION
AB Originally identified as an innate cytotoxin, nitric oxide ((NO)-N-center dot) formation in tumors can influence chemotherapy and exacerbate cancer progression. Here, we examined the hypothesis that (NO)-N-center dot generation contributes to cancer cell drug resistance toward the widely used anticancer drug Etoposide (VP-16). The UV-vis spectrum of VP-16 was not changed by exposure of VP-16 to (NO)-N-center dot in aqueous buffer. In contrast, reddish-orange compound(s) characteristic of o-quinone- and nitroso-VP-16 were readily generated in a hydrophobic medium (chloroform) in an oxygen-dependent manner. Similar products were also formed when the VP-16 radical, generated from VP-16 and horseradish peroxidase/H2O2, was exposed directly to (NO)-N-center dot in chloroform in the presence of oxygen. Separation and spectral analysis of VP-16 reaction extracts by electron spin resonance and UV-vis indicated the generation of the phenoxy radical and the o-quinone of VP-16, as well as putative nitroxide, iminoxyl, and other nitrogen oxide intermediates. Nitric oxide products of VP-16 displayed significantly diminished topoisomerase II-dependent cleavage of DNA and cytotoxicity to human HL-60 leukemia cells. LPS-mediated induction of nitric oxide synthase in murine macrophages resulted in VP-16 resistance compared to Raw cells. Furthermore, (NO)-N-center dot products derived from iNOS rapidly reacted with VP-16 leading to decreased DNA damage and cytotoxicity. Together, these observations suggest that the formation of (NO)-N-center dot in tumors (associated macrophages) can contribute to VP-16 resistance via the detoxification of VP-16.
C1 [Sinha, Birandra K.; Bhattacharjee, Suchandra; Chatterjee, Saurabh; Jiang, JinJie; Motten, Ann G.; Kumar, Ashutosh; Mason, Ronald P.] NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA.
[Espey, Michael Graham] NIDDK, Off Sci Director, NIH, Bethesda, MD USA.
RP Sinha, BK (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM sinha1@niehs.nih.gov
FU Intramural Research Program of the NIH; NIH/NIEHS; NIH; Pathway to
Independence Award [ES01-19875A]; [K99-R00]
FX This research was supported by the Intramural Research Program of the
NIH, and NIH/NIEHS. S.C. is also supported by a K99-R00, NIH, and
Pathway to Independence Award (ES01-19875A).
NR 64
TC 4
Z9 4
U1 1
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0893-228X
J9 CHEM RES TOXICOL
JI Chem. Res. Toxicol.
PD MAR
PY 2013
VL 26
IS 3
BP 379
EP 387
DI 10.1021/tx300480q
PG 9
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA 110JU
UT WOS:000316439200008
PM 23402364
ER
PT J
AU Jacobs, SR
Weiner, BJ
Minasian, LM
Good, MJ
AF Jacobs, Sara R.
Weiner, Bryan J.
Minasian, Lori M.
Good, Marjorie J.
TI Achieving high cancer control trial enrollment in the community setting:
An analysis of the Community Clinical Oncology Program
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Cancer; Clinical trial enrollment; Cancer symptom control; Community
Clinical Oncology Program
ID SYMPTOMS; CARE
AB Determining the factors that lead to successful enrollment of patients in cancer control clinical trials is essential as cancer patients are often burdened with side effects such as pain, nausea, and fatigue. One promising intervention for increasing enrollment in cancer control trials is the National Cancer Institute's Community Clinical Oncology Program (CCOP). In this article, we examined CCOP staffing, policies, and procedures associated with enrollment in control trials. Data were obtained from three sources: the online CCOP, MB-CCOP, and Research Base Management System, CCOP Annual Progress Reports, and a survey of CCOP Administrators conducted in 2011. We analyzed cancer control trial accrual in 2011 among 46 CCOPs using multivariate regression. Three factors were significant predictors of accrual. First, having a team of staff dedicated to enrolling patients in control and prevention trials, compared to having no dedicated staff, was associated on average with an additional 30 patients enrolled in control trials (p<0.05). Second, CCOPs that recognized physicians for enrolling a large number of patients compared to CCOPs that did not recognize high enrolling physicians enrolled on average an additional 25 patients in control trials (p<0.05). Lastly, the number of cancer control trials available was also associated with enrollment (beta=5.50, p<0.00). Our results indicate that CCOPs looking to increase enrollment in control trials should consider dedicating a team of staff to enroll patients in these types of trials. In addition, CCOPs or other volunteer research systems looking to increase physician participation should consider recognizing high enrolling physicians. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Jacobs, Sara R.; Weiner, Bryan J.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC 27599 USA.
[Weiner, Bryan J.] Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA.
[Minasian, Lori M.; Good, Marjorie J.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Jacobs, SR (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, 1101 McGavran Greenberg Hall,CB 7411, Chapel Hill, NC 27599 USA.
EM jacobssr@live.unc.edu
FU National Cancer Institute at the National Institutes of Health
[R25CA116339, R01CA124402]
FX This work was supported by the National Cancer Institute at the National
Institutes of Health (R25CA116339 and R01CA124402).
NR 15
TC 6
Z9 6
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD MAR
PY 2013
VL 34
IS 2
BP 320
EP 325
DI 10.1016/j.cct.2012.12.008
PG 6
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 120KL
UT WOS:000317169100017
PM 23295315
ER
PT J
AU Murray, DM
Katz, ML
Post, DM
Pennell, ML
Young, GS
Tatum, CM
Paskett, ED
AF Murray, David M.
Katz, Mira L.
Post, Doug M.
Pennell, Michael L.
Young, Gregory S.
Tatum, Cathy M.
Paskett, Electra D.
TI Enhancing cancer screening in primary care: Rationale, design, analysis
plan, and recruitment results
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Colorectal cancer; Screening; Group-randomized trial
ID RANDOM-EFFECTS MODELS; LINEAR MIXED MODELS; COLORECTAL-CANCER;
MAXIMUM-LIKELIHOOD; RANDOMIZED-TRIALS; HEALTH; GUIDELINES; INFERENCE;
RESPONSES; SERVICES
AB Colorectal cancer (CRC) is the third leading type of cancer and the third leading cause of cancer death in the United States. National policy-making organizations recognize and support a variety of CRC screening strategies among average-risk adults aged 50 and older based on strong evidence showing that screening decreases mortality from CRC and can also reduce the incidence of the disease. The goal of this study was to test a multi-level stepped intervention to increase CRC screening rates. We used a group-randomized trial design where the units of assignment were clinics and the units of observation were eligible patients receiving care at those clinics, with stratified random assignment of clinics to study conditions. The primary analysis was planned as a mixed-model logistic regression to account for the expected positive intraclass correlation associated with clinics. Our recruitment experience reflected the difficulties of conducting research in the real world where changes in economic conditions, staff turnover/layoff, inadequate medical records, and poor acceptance of research can significantly impact study plans. It demonstrated the problems that can emerge when procedures used in the study depart from those used in the pilot work to generate parameter estimates for power analysis. It also demonstrated the importance of allowing for attrition at the group and patient levels so that if recruitment falls short, it is possible to maintain adequate power with only a slight increase in the detectable difference. This experience should assist others planning group-randomized trials, whether in cancer screening or in other areas. Published by Elsevier Inc.
C1 [Murray, David M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Biostat & Bioinformat Branch, NIH, Bethesda, MD 20892 USA.
[Katz, Mira L.] Ohio State Univ, Coll Publ Hlth, Div Hlth Behav & Hlth Promot, Columbus, OH 43210 USA.
[Pennell, Michael L.] Ohio State Univ, Coll Publ Hlth, Div Biostat, Columbus, OH 43210 USA.
[Paskett, Electra D.] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA.
[Young, Gregory S.] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA.
[Post, Doug M.] Ohio State Univ, Coll Med, Dept Family Med, Columbus, OH 43210 USA.
[Katz, Mira L.; Tatum, Cathy M.; Paskett, Electra D.] Ohio State Univ, Coll Med, Dept Internal Med, Div Canc Prevent & Control, Columbus, OH 43210 USA.
[Katz, Mira L.; Post, Doug M.; Tatum, Cathy M.; Paskett, Electra D.] Ohio State Univ, Ctr Comprehens Canc, Div Populat Sci, Columbus, OH 43210 USA.
RP Murray, DM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Biostat & Bioinformat Branch, NIH, 6100 Execut Blvd,Room 2B03, Bethesda, MD 20892 USA.
EM david.murray2@nih.gov
FU National Cancer Institute [R01 CA116487, P30 CA016058, K07 CA107079]
FX This study was supported by Research Grants R01 CA116487 and P30
CA016058 (to E.D. Paskett), and K07 CA107079 (to M.L. Katz) 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.
NR 45
TC 1
Z9 1
U1 1
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD MAR
PY 2013
VL 34
IS 2
BP 356
EP 363
DI 10.1016/j.cct.2013.01.003
PG 8
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 120KL
UT WOS:000317169100021
PM 23357561
ER
PT J
AU Levy, G
Hill, MJ
Plowden, TC
Catherino, WH
Armstrong, AY
AF Levy, Gary
Hill, Micah J.
Plowden, Torie C.
Catherino, William H.
Armstrong, Alicia Y.
TI Biomarkers in uterine leiomyoma
SO FERTILITY AND STERILITY
LA English
DT Article; Proceedings Paper
CT 1st Reproductive Biomarker Meeting
CY MAR 30-31, 2012
CL Valencia, SPAIN
DE Leiomyoma; fibroids; biomarker
ID EPITHELIAL OVARIAN-CANCER; SERUM CA 125; TRANSVAGINAL SONOGRAPHY;
DIFFERENTIAL-DIAGNOSIS; PELVIC MASS; HLA-G; GROWTH; FIBROIDS; MYOMAS;
RECEPTOR
AB Biomarkers are biologic compounds that are easily accessible and reflect normal physiology or pathology. They are useful in a variety of clinical situations that involve detection of subclinical disease, risk stratification, preoperative planning, and monitoring treatment. A useful intervention needs to exist for a biomarker to be an effective tool. Many compounds have been investigated as potential biomarkers for the diagnosis and surveillance of uterine leiomyomas. Most of these compounds demonstrate subtle differences among patients when leiomyomas are compared with controls. The compounds investigated lack the diagnostic accuracy necessary to add any benefit to the current available modalities used to diagnose and monitor uterine leiomyomas. (Fertil Steril (R) 2013;99:1146-52. (C) 2013 by American Society for Reproductive Medicine.)
C1 [Levy, Gary; Hill, Micah J.; Catherino, William H.; Armstrong, Alicia Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Plowden, Torie C.] Bayne Jones Army Community Hosp, Ft Polk, LA USA.
[Catherino, William H.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
RP Armstrong, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, 10 Ctr Dr,Room 1-3140,MSC 1109, Bethesda, MD 20892 USA.
EM aa257w@nih.gov
FU National Institutes of Health, Program in Reproductive and Adult
Endocrinology, National Institute of Child Health and Human Development,
Bethesda, Maryland
FX Supported in part by the National Institutes of Health, Program in
Reproductive and Adult Endocrinology, National Institute of Child Health
and Human Development, Bethesda, Maryland.
NR 72
TC 6
Z9 7
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD MAR
PY 2013
VL 99
IS 4
BP 1146
EP 1152
DI 10.1016/j.fertnstert.2012.10.048
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 113JP
UT WOS:000316663300024
PM 23200685
ER
PT J
AU Cong, M
Hu, CM
Cao, YF
Fang, ZZ
Tang, SH
Wang, JR
Luo, JS
AF Cong, Ming
Hu, Cui-Min
Cao, Yun-Feng
Fang, Zhong-Ze
Tang, Shu-Hong
Wang, Jia-Rui
Luo, Jun-Sheng
TI Cryptotanshinone and dihydrotanshinone I exhibit strong inhibition
towards human liver microsome (HLM)-catalyzed propofol glucuronidation
SO FITOTERAPIA
LA English
DT Article
DE Danshen; UDP-glucuronosyltransferases (UGTs); Herb-drug interaction
ID UDP-GLUCURONOSYLTRANSFERASE ISOFORMS; SALVIA-MILTIORRHIZA;
SUPRAVENTRICULAR TACHYCARDIA; TANSHINONE IIA; IDENTIFICATION;
CONSTITUENTS; CHEMISTRY
AB Danshen is one of the most famous herbs in the world, and more and more danshen-prescribed drugs interactions have been reported in recent years. Evaluation of inhibition potential of danshen's major ingredients towards UDP-glucuronosyltransferases (UGTs) will be helpful for understanding detailed mechanisms for danshen-drugs interaction. Therefore, the aim of the present study is to investigate the inhibitory situation of cryptotanshinone and dihydrotanshinone I towards UGT enzyme-catalyzed propofol glucuronidation. In vitro the human liver microsome (HLM) incubation system was used, and the results showed that cryptotanshinone and dihydrotanshinone I exhibited dose-dependent inhibition towards HLM-catalyzed propofol glucuronidation. Dixon plot and Lineweaver-Burk plot showed that the inhibition type was best fit to competitive inhibition type for both cryptotanshinone and dihydrotanshinone I. The second plot using the slopes from the Lineweaver-Burk plot versus the concentrations of cryptotanshinone or dihydrotanshinone I was employed to calculate the inhibition parameters (K-1) to be 0.4 and 1.7 mu M, respectively. Using the reported maximum plasma concentration (C-max), the altered in vivo exposure of propofol increased by 10% and 8.2% for the co-administration of dihydrotanshinone I and cryptotanshinone, respectively. All these results indicated the possible danshen-propofol interaction due to the inhibition of dihydrotanshinone I and cryptotanshinone towards the glucuronidation reaction of propofol. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Cong, Ming; Luo, Jun-Sheng] Liaoning Med Univ, Affiliated Hosp 1, Jinzhou 121001, Peoples R China.
[Cao, Yun-Feng; Fang, Zhong-Ze] Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian 116023, Peoples R China.
[Cao, Yun-Feng; Fang, Zhong-Ze] Liaoning Med Univ, Affiliated Hosp 1, Dalian 116023, Peoples R China.
[Tang, Shu-Hong; Wang, Jia-Rui] Fifth Hosp Dalian, Dept Oncol, Dalian 116021, Peoples R China.
[Hu, Cui-Min; Fang, Zhong-Ze] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Luo, JS (reprint author), Liaoning Med Univ, Affiliated Hosp 1, Jinzhou 121001, Peoples R China.
EM luojunshengljs@sina.com
NR 30
TC 15
Z9 16
U1 3
U2 23
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0367-326X
J9 FITOTERAPIA
JI Fitoterapia
PD MAR
PY 2013
VL 85
BP 109
EP 113
DI 10.1016/j.fitote.2013.01.002
PG 5
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 120LO
UT WOS:000317172000016
PM 23333907
ER
PT J
AU He, B
Baird, R
Butera, R
Datta, A
George, S
Hecht, B
Hero, A
Lazzi, G
Lee, RC
Liang, J
Neuman, M
Peng, GCY
Perreault, EJ
Ramasubramanian, M
Wang, MD
Wikswo, J
Yang, GZ
Zhang, YT
AF He, Bin
Baird, Richard
Butera, Robert
Datta, Aniruddha
George, Steven
Hecht, Bruce
Hero, Alfred
Lazzi, Gianluca
Lee, Raphael C.
Liang, Jie
Neuman, Michael
Peng, Grace C. Y.
Perreault, Eric J.
Ramasubramanian, Melur
Wang, May D.
Wikswo, John
Yang, Guang-Zhong
Zhang, Yuan-Ting
TI Grand Challenges in Interfacing Engineering With Life Sciences and
Medicine
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Bioengineering; biomedical engineering; engineering; grand challenges;
healthcare; life science; medicine
ID BIOLOGY
AB This paper summarizes the discussions held during the First IEEE Life Sciences Grand Challenges Conference, held on October 4-5, 2012, at the National Academy of Sciences, Washington, DC, and the grand challenges identified by the conference participants. Despite tremendous efforts to develop the knowledge and ability that are essential in addressing biomedical and health problems using engineering methodologies, the optimization of this approach toward engineering the life sciences and healthcare remains a grand challenge. The conference was aimed at high-level discussions by participants representing various sectors, including academia, government, and industry. Grand challenges were identified by the conference participants in five areas including engineering the brain and nervous system; engineering the cardiovascular system; engineering of cancer diagnostics, therapeutics, and prevention; translation of discoveries to clinical applications; and education and training. A number of these challenges are identified and summarized in this paper.
C1 [He, Bin] Univ Minnesota, Inst Engn Med, Minneapolis, MN 55455 USA.
[Baird, Richard; Peng, Grace C. Y.] NIBIB, NIH, Bethesda, MD 20892 USA.
[Butera, Robert] Georgia Inst Technol, Sch Elect & Comp Engn, Atlanta, GA 30332 USA.
[Datta, Aniruddha] Texas A&M Univ, College Stn, TX 77840 USA.
[George, Steven] Univ Calif Irvine, Irvine, CA 92697 USA.
[Hecht, Bruce] Analog Devices Inc, Norwood, MA 02062 USA.
[Hero, Alfred] Univ Michigan, Ann Arbor, MI 48109 USA.
[Lazzi, Gianluca] Univ Utah, Salt Lake City, UT 84112 USA.
[Lee, Raphael C.] Univ Chicago, Chicago, IL 60637 USA.
[Liang, Jie] Univ Illinois, Chicago, IL 60607 USA.
[Neuman, Michael] Michigan Technol Univ, Houghton, MI 49931 USA.
[Perreault, Eric J.] Northwestern Univ, Chicago, IL 60611 USA.
[Ramasubramanian, Melur] Clemson Univ, Clemson, SC 29634 USA.
[Wang, May D.] Georgia Inst Technol, Atlanta, GA 30332 USA.
[Wang, May D.] Emory Univ, Atlanta, GA 30332 USA.
[Wikswo, John] Vanderbilt Univ, Nashville, TN 37235 USA.
[Yang, Guang-Zhong] Univ London Imperial Coll Sci Technol & Med, Hamlyn Ctr, London SW7 2AZ, England.
[Zhang, Yuan-Ting] Chinese Univ Hong Kong, Joint Res Ctr Biomed Engn, Shatin, Hong Kong, Peoples R China.
[Zhang, Yuan-Ting] SIAT, Key Lab Hlth Informat, Chinese Acad Sci, Shenzhen, Peoples R China.
RP He, B (reprint author), Univ Minnesota, Inst Engn Med, Minneapolis, MN 55455 USA.
EM binhe@umn.edu; bairdri@mail.nih.gov; rbutera@gatech.edu;
datta@ece.tamu.edu; scgeorge@uci.edu; Bruce.Hecht@analog.com;
hero@umich.edu; lazzi@utah.edu; rlee@surgery.bsd.uchicago.edu;
jliang@uic.edu; mneuman@mtu.edu; penggr@mail.nih.gov;
e-perreault@northwestern.edu; rammk@clemson.edu; maywang@bme.gatech.edu;
john.wikswo@vanderbilt.edu; g.z.yang@imperial.ac.uk;
ytzhang@ee.cuhk.edu.hk
RI Perreault, Eric/B-7632-2009;
OI Butera, Robert/0000-0002-1806-0621
FU National Science Foundation [CBET-1206695]; Institute for Engineering in
Medicine of the University of Minnesota
FX This work was organized by the IEEE and was supported in part by the
National Science Foundation under Grant CBET-1206695 and in part by the
Institute for Engineering in Medicine of the University of Minnesota.
NR 14
TC 20
Z9 21
U1 4
U2 42
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD MAR
PY 2013
VL 60
IS 3
BP 589
EP 598
DI 10.1109/TBME.2013.2244886
PG 10
WC Engineering, Biomedical
SC Engineering
GA 115KL
UT WOS:000316810900002
PM 23380847
ER
PT J
AU Karasek, D
Shah, U
Frysak, Z
Stratakis, C
Pacak, K
AF Karasek, D.
Shah, U.
Frysak, Z.
Stratakis, C.
Pacak, K.
TI An update on the genetics of pheochromocytoma
SO JOURNAL OF HUMAN HYPERTENSION
LA English
DT Review
DE pheochromocytoma; paraganglioma; genes; catecholamines; metanephrines
ID HIPPEL-LINDAU-DISEASE; SUCCINATE-DEHYDROGENASE; GERMLINE MUTATIONS;
NEUROFIBROMATOSIS TYPE-1; TUMOR-SUPPRESSOR; FAMILIAL PHEOCHROMOCYTOMA;
CLINICAL-FEATURES; PARAGANGLIOMAS; SDHB; DIAGNOSIS
AB Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendocrine tumors. About 30% or more of them are thought to be of inherited origin due to germ-line mutations in at least 10 well-characterized genes. There are data linking specific genotypes of these tumors to specific locations, typical biochemical phenotypes or future clinical behaviors. Conversely, clinical features, catecholamine production and immunohistochemistry evaluation can help with the proper order of genetic testing for PHEO and PGL. The identification of a germ-line mutation can lead to an early diagnosis, appropriate treatment, regular surveillance and better prognosis not only for the patient but also for their family members. Moreover, the latest discoveries in molecular pathogenesis of these tumors will provide an important basis for future personalized therapy. Journal of Human Hypertension (2013) 27, 141-147; doi: 10.1038/jhh.2012.20; published online 31 May 2012
C1 [Karasek, D.; Frysak, Z.] Univ Hosp Olomouc, Dept Internal Med 3, Olomouc, Czech Republic.
[Shah, U.; Pacak, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Stratakis, C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Pacak, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC, Bldg 10,1 East,Room 1-3140,10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, MD, USA
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, MD, USA.
NR 60
TC 19
Z9 22
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9240
J9 J HUM HYPERTENS
JI J. Hum. Hypertens.
PD MAR
PY 2013
VL 27
IS 3
BP 141
EP 147
DI 10.1038/jhh.2012.20
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 119SI
UT WOS:000317117500001
PM 22648268
ER
PT J
AU Jacob, KD
Noren Hooten, N
Trzeciak, AR
Evans, MK
AF Jacob, Kimberly D.
Noren Hooten, Nicole
Trzeciak, Andrzej R.
Evans, Michele K.
TI Markers of oxidant stress that are clinically relevant in aging and
age-related disease
SO MECHANISMS OF AGEING AND DEVELOPMENT
LA English
DT Review
DE DNA oxidation; RNA oxidation; Protein oxidation; Single strand breaks;
CRP
ID OXIDATIVE DNA-DAMAGE; C-REACTIVE PROTEIN; ALKALINE COMET ASSAY;
DOUBLE-STRAND BREAKS; CEREBROSPINAL-FLUID F-2-ISOPROSTANES; DEPENDENT
DIABETES-MELLITUS; HEME DEGRADATION-PRODUCTS; TANDEM MASS-SPECTROMETRY;
NEURONAL RNA OXIDATION; HUMAN SKELETAL-MUSCLE
AB Despite the long held hypothesis that oxidant stress results in accumulated oxidative damage to cellular macromolecules and subsequently to aging and age-related chronic disease, it has been difficult to consistently define and specifically identify markers of oxidant stress that are consistently and directly linked to age and disease status. Inflammation because it is also linked to oxidant stress, aging, and chronic disease also plays an important role in understanding the clinical implications of oxidant stress and relevant markers. Much attention has focused on identifying specific markers of oxidative stress and inflammation that could be measured in easily accessible tissues and fluids (lymphocytes, plasma, serum). The purpose of this review is to discuss markers of oxidant stress used in the field as biomarkers of aging and age-related diseases, highlighting differences observed by race when data is available. We highlight DNA, RNA, protein, and lipid oxidation as measures of oxidative stress, as well as other well-characterized markers of oxidative damage and inflammation and discuss their strengths and limitations. We present the current state of the literature reporting use of these markers in studies of human cohorts in relation to age and age-related disease and also with a special emphasis on differences observed by race when relevant. Published by Elsevier Ireland Ltd.
C1 [Jacob, Kimberly D.; Noren Hooten, Nicole; Evans, Michele K.] NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA.
[Trzeciak, Andrzej R.] NIDA, Mol Neurobiol Res Branch, NIH, Baltimore, MD USA.
RP Evans, MK (reprint author), NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA.
EM me42v@nih.gov
OI Noren Hooten, Nicole/0000-0002-1683-3838
FU Intramural Research Program of the NIH, National Institute on Aging
FX We thank Dr. David Wilson III and Dr. Joseph Rifkind for critical
reading of the manuscript. Research in this laboratory is supported by
the Intramural Research Program of the NIH, National Institute on Aging.
NR 275
TC 68
Z9 69
U1 3
U2 44
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0047-6374
J9 MECH AGEING DEV
JI Mech. Ageing Dev.
PD MAR-APR
PY 2013
VL 134
IS 3-4
BP 139
EP 157
DI 10.1016/j.mad.2013.02.008
PG 19
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 120DH
UT WOS:000317150500009
PM 23428415
ER
PT J
AU Bertola, A
Mathews, S
Ki, SH
Wang, H
Gao, B
AF Bertola, Adeline
Mathews, Stephanie
Ki, Sung Hwan
Wang, Hua
Gao, Bin
TI Mouse model of chronic and binge ethanol feeding (the NIAAA model)
SO NATURE PROTOCOLS
LA English
DT Article
ID ALCOHOLIC LIVER-DISEASE; OXIDATIVE STRESS; INTRAGASTRIC INFUSION;
HEPATIC STEATOSIS; FATTY LIVER; TNF-ALPHA; FED MICE; INJURY;
PATHOGENESIS; STEATOHEPATITIS
AB Chronic alcohol consumption is a leading cause of chronic liver disease worldwide, leading to cirrhosis and hepatocellular carcinoma. Currently, the most widely used model for alcoholic liver injury is ad libitum feeding with the Lieber-DeCarli liquid diet containing ethanol for 4-6 weeks; however, this model, without the addition of a secondary insult, only induces mild steatosis, slight elevation of serum alanine transaminase (ALT) and little or no inflammation. Here we describe a simple mouse model of alcoholic liver injury by chronic ethanol feeding (10-d ad libitum oral feeding with the Lieber-DeCarli ethanol liquid diet) plus a single binge ethanol feeding. This protocol for chronic-plus-single-binge ethanol feeding synergistically induces liver injury, inflammation and fatty liver, which mimics acute-on-chronic alcoholic liver injury in patients. This feeding protocol can also be extended to chronic feeding for longer periods of time up to 8 weeks plus single or multiple binges. Chronic-binge ethanol feeding leads to high blood alcohol levels; thus, this simple model will be very useful for the study of alcoholic liver disease (ALD) and of other organs damaged by alcohol consumption.
C1 [Bertola, Adeline; Mathews, Stephanie; Ki, Sung Hwan; Wang, Hua; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
EM bgao@mail.nih.gov
OI Bertola, Adeline/0000-0002-4885-8423
FU NIAAA at the NIH
FX We greatly appreciate all current and previous lab members for their
technical support and helpful discussions. We also thank L. Chedester,
A. Barnes and R. Kechrid from the Office of Laboratory Animal Science
for their technical and engineering support, and for their critical
reading of the manuscript. This work is supported by the intramural
program of NIAAA at the NIH.
NR 44
TC 107
Z9 114
U1 6
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
J9 NAT PROTOC
JI Nat. Protoc.
PD MAR
PY 2013
VL 8
IS 3
BP 627
EP 637
DI 10.1038/nprot.2013.032
PG 11
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 119PU
UT WOS:000317110600015
PM 23449255
ER
PT J
AU Knutson, KM
Rakowsky, ST
Solomon, J
Krueger, F
Raymont, V
Tierney, MC
Wassermann, EM
Grafman, J
AF Knutson, Kristine M.
Rakowsky, Shana T.
Solomon, Jeffrey
Krueger, Frank
Raymont, Vanessa
Tierney, Michael C.
Wassermann, Eric M.
Grafman, Jordan
TI Injured brain regions associated with anxiety in Vietnam veterans
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Anxiety; Traumatic brain injury; Voxel-based lesion symptom mapping
ID POSTTRAUMATIC-STRESS-DISORDER; PENETRATING HEAD-INJURY; AVERSIVE
VISUAL-STIMULI; BED NUCLEUS; ORBITOFRONTAL CORTEX; BASOLATERAL AMYGDALA;
HIPPOCAMPAL-LESIONS; PREFRONTAL CORTEX; STRIA TERMINALIS; FUNCTIONAL
NEUROANATOMY
AB Anxiety negatively affects quality of life and psychosocial functioning. Previous research has shown that anxiety symptoms in healthy individuals are associated with variations in the volume of brain regions, such as the amygdala, hippocampus, and the bed nucleus of the stria terminalis. Brain lesion data also suggests the hemisphere damaged may affect levels of anxiety. We studied a sample of 182 male Vietnam War veterans with penetrating brain injuries, using a semi-automated voxel-based lesion-symptom mapping (VLSM) approach. VLSM reveals significant associations between a symptom such as anxiety and the location of brain lesions, and does not require a broad, subjective assignment of patients into categories based on lesion location. We found that lesioned brain regions in cortical and limbic areas of the left hemisphere, including middle, inferior and superior temporal lobe, hippocampus, and fusiform regions, along with smaller areas in the inferior occipital lobe, parahippocampus, amygdala, and insula, were associated with increased anxiety symptoms as measured by the Neurobehavioral Rating Scale (NRS). These results were corroborated by similar findings using Neuropsychiatric Inventory (NPI) anxiety scores, which supports these regions' role in regulating anxiety.
In summary, using a semi-automated analysis tool, we detected an effect of focal brain damage on the presentation of anxiety. We also separated the effects of brain injury and war experience by including a control group of combat veterans without brain injury. We compared this control group against veterans with brain lesions in areas associated with anxiety, and against veterans with lesions only in other brain areas. Published by Elsevier Ltd.
C1 [Knutson, Kristine M.; Tierney, Michael C.; Wassermann, Eric M.] NINDS, Behav Neurol Unit, NIH, Bethesda, MD 20892 USA.
[Rakowsky, Shana T.] Georgetown Univ, Georgetown Coll, Washington, DC USA.
[Solomon, Jeffrey] Expert Image Anal LLC, Potomac, MD USA.
[Krueger, Frank] George Mason Univ, Dept Mol Neurosci, Fairfax, VA 22030 USA.
[Krueger, Frank] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
[Raymont, Vanessa] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England.
[Raymont, Vanessa] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA.
[Grafman, Jordan] Rehabil Inst Chicago, Brain Injury Res Program, Chicago, IL 60611 USA.
RP Knutson, KM (reprint author), NINDS, Behav Neurol Unit, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM knutsonk@ninds.nih.gov; jgrafman@ric.org
OI Knutson, Kristine/0000-0003-4626-4514; Grafman, Jordan
H./0000-0001-8645-4457
FU United States National Institutes of Health, National Institute of
Neurological Disorders and Stroke, intramural research program; United
States Army Medical Research and Material Command [DAMD17-01-1-0675]
FX We especially thank the Vietnam War veterans who participated in this
study. We thank the National Naval Medical Center for their support and
provision of their facilities and S. Bonifant, B. Cheon, C. Ngo, A.
Greathouse, K. Reding, and G. Tasick for their invaluable help with the
testing of participants and organization of this study. The work was
supported by the United States National Institutes of Health, National
Institute of Neurological Disorders and Stroke, intramural research
program, and a project grant from the United States Army Medical
Research and Material Command administrated by the Henry M. Jackson
Foundation (Vietnam Head Injury Study Phase III: a 30-year post-injury
follow-up study, Grant DAMD17-01-1-0675). The views expressed in this
article are those of the authors and do not necessarily reflect the
official policy or position of the Department of the Navy, the
Department of Defense, nor the United States Government.
NR 120
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Z9 7
U1 4
U2 15
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD MAR
PY 2013
VL 51
IS 4
BP 686
EP 694
DI 10.1016/j.neuropsychologia.2013.01.003
PG 9
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 121PV
UT WOS:000317257600012
PM 23328629
ER
PT J
AU Damiano, DL
Prosser, LA
Curatalo, LA
Alter, KE
AF Damiano, Diane L.
Prosser, Laura A.
Curatalo, Lindsey A.
Alter, Katharine E.
TI Muscle Plasticity and Ankle Control After Repetitive Use of a Functional
Electrical Stimulation Device for Foot Drop in Cerebral Palsy
SO NEUROREHABILITATION AND NEURAL REPAIR
LA English
DT Article
DE cerebral palsy; electrical stimulation; gait; ankle; ultrasound; muscle
thickness; cross-sectional area
ID STRENGTH; CHILDREN; GAIT; ARCHITECTURE; FES
AB Background/Objectives. The primary goal was to determine whether repetitive functional electrical stimulation (FES) for unilateral foot drop increases tibialis anterior (TA) muscle size compared with an untreated baseline and the contralateral side in cerebral palsy (CP). Secondary goals were to determine whether positive changes in muscle size and gait, if found, accumulated during the 3 intervals during which participants used the device. FES devices differ from traditional orthoses that often restrict muscle activation and may exacerbate weakness, promote continued dependence on orthoses, or precipitate functional decline. Methods. Participants were 14 independent ambulators with inadequate dorsiflexion in swing, with a mean age of 13.1 years, evaluated before and after the 3-month baseline, 1-month device accommodation, 3-month primary intervention, and 3-month follow-up phases. The FES device (WalkAide) stimulated the common fibular nerve to dorsiflex the ankle and evert the foot while monitoring use. TA muscle ultrasound, gait velocity, and ankle kinematic data for barefoot and device conditions are reported. Results. Ultrasound measures of TA anatomic cross-sectional area and muscle thickness increased in the intervention compared with baseline and with the contralateral side and were maintained at follow-up. Maximum ankle dorsiflexion decreased at baseline but improved or was maintained during the intervention phase with and without the device, respectively. Muscle size gains were preserved at follow-up, but barefoot ankle motion returned to baseline values. Conclusions. This FES device produced evidence of use-dependent muscle plasticity in CP. Permanent improvements in voluntary ankle control after repetitive stimulation were not demonstrated.
C1 [Damiano, Diane L.; Curatalo, Lindsey A.; Alter, Katharine E.] NIH, Bethesda, MD 20814 USA.
[Prosser, Laura A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Alter, Katharine E.] Mt Washington Pediat Hosp, Baltimore, MD USA.
RP Damiano, DL (reprint author), NIH, 10 Ctr Dr,MSC 1604, Bethesda, MD 20814 USA.
EM damianod@cc.nih.gov
RI Prosser, Laura/C-1242-2009; Van Mulders, Benjamin/P-1241-2014; Damiano,
Diane/B-3338-2010
OI Damiano, Diane/0000-0002-2770-5356
FU Intramural Research Program at the NIH Clinical Center
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This work
was supported by the Intramural Research Program at the NIH Clinical
Center. Innovative Neurotronics provided the devices to all
participants.
NR 20
TC 14
Z9 15
U1 0
U2 17
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1545-9683
J9 NEUROREHAB NEURAL RE
JI Neurorehabil. Neural Repair
PD MAR-APR
PY 2013
VL 27
IS 3
BP 200
EP 207
DI 10.1177/1545968312461716
PG 8
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 118WY
UT WOS:000317058600002
PM 23042834
ER
PT J
AU Starks, AM
Martin, DN
Dorsey, TH
Boersma, BJ
Wallace, TA
Ambs, S
AF Starks, Adrienne M.
Martin, Damali N.
Dorsey, Tiffany H.
Boersma, Brenda J.
Wallace, Tiffany A.
Ambs, Stefan
TI Household Income Is Associated with the p53 Mutation Frequency in Human
Breast Tumors
SO PLOS ONE
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; TP53 GENE-MUTATIONS; AFRICAN-AMERICAN; CANCER
PATIENTS; MOLECULAR PATHOGENESIS; SOCIOECONOMIC-STATUS; RACIAL
DISPARITIES; EPITHELIAL-CELLS; SUPPRESSOR GENE; POOR-PROGNOSIS
AB Background: A study from Scotland reported that the p53 mutation frequency in breast tumors is associated with socioeconomic deprivation.
Methods: We analyzed the association of the tumor p53 mutational status with tumor characteristics, education, and self-reported annual household income (HI) among 173 breast cancer patients from the greater Baltimore area, United States.
Results: p53 mutational frequency was significantly associated with HI. Patients with < $15,000 HI had the highest p53 mutation frequency (21%), followed by the income group between $15,000 and $60,000 (18%), while those above $60,000 HI had the fewest mutations (5%). When dichotomized at $60,000, 26 out of 135 patients in the low income category had acquired a p53 mutation, while only 2 out of 38 with a high income carried a mutation (P<0.05). In the adjusted logistic regression analysis with 3 income categories (trend test), the association between HI and p53 mutational status was independent of tumor characteristics, age, race/ethnicity, tobacco smoking and body mass. Further analyses revealed that HI may impact the p53 mutational frequency preferentially in patients who develop an estrogen receptor (ER)-negative disease. Within this group, 42% of the low income patients (<$15,000 HI) carried a mutation, followed by the middle income group (21%), while those above $60,000 HI did not carry mutations (P-trend < 0.05).
Conclusions: HI is associated with the p53 mutational frequency in patients who develop an ER-negative disease. Furthermore, high income patients may acquire fewer p53 mutations than other patients, suggesting that lifetime exposures associated with socio-economic status may impact breast cancer biology.
C1 [Starks, Adrienne M.; Dorsey, Tiffany H.; Boersma, Brenda J.; Wallace, Tiffany A.; Ambs, Stefan] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Martin, Damali N.] NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
RP Ambs, S (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM ambss@mail.nih.gov
RI Boersma, Brenda/A-9270-2009
OI Boersma, Brenda/0000-0002-8992-2735
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research, United States of
America
FX The research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research, United States of America. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 50
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Z9 5
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 MAR 1
PY 2013
VL 8
IS 3
AR e57361
DI 10.1371/journal.pone.0057361
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 103EI
UT WOS:000315897100019
PM 23469190
ER
PT J
AU Alivisatos, AP
Andrews, AM
Boyden, ES
Chun, M
Church, GM
Deisseroth, K
Donoghue, JP
Fraser, SE
Lippincott-Schwartz, J
Looger, LL
Masmanidis, S
McEuen, PL
Nurmikko, AV
Park, H
Peterka, DS
Reid, C
Roukes, ML
Scherer, A
Schnitzer, M
Sejnowski, TJ
Shepard, KL
Tsao, D
Turrigiano, G
Weiss, PS
Xu, C
Yuste, R
Zhuang, XW
AF Alivisatos, A. Paul
Andrews, Anne M.
Boyden, Edward S.
Chun, Miyoung
Church, George M.
Deisseroth, Karl
Donoghue, John P.
Fraser, Scott E.
Lippincott-Schwartz, Jennifer
Looger, Loren L.
Masmanidis, Sotiris
McEuen, Paul L.
Nurmikko, Arto V.
Park, Hongkun
Peterka, Darcy S.
Reid, Clay
Roukes, Michael L.
Scherer, Axel
Schnitzer, Mark
Sejnowski, Terrence J.
Shepard, Kenneth L.
Tsao, Doris
Turrigiano, Gina
Weiss, Paul S.
Xu, Chris
Yuste, Rafael
Zhuang, Xiaowei
TI Nanotools for Neuroscience and Brain Activity Mapping
SO ACS NANO
LA English
DT Article
ID SELF-ASSEMBLED MONOLAYERS; REDUCED SEROTONIN TRANSPORTER; VENTRAL
TEGMENTAL AREA; IMAGING-DEPTH LIMIT; IN-VIVO; NEURAL CIRCUITS;
MICROELECTRODE ARRAYS; ACTION-POTENTIALS; ELECTRODE ARRAYS; TEMPORAL
RESOLUTION
AB Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations In current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there Is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and In the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function.
C1 [Alivisatos, A. Paul] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
[Alivisatos, A. Paul] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
[Andrews, Anne M.; Masmanidis, Sotiris; Weiss, Paul S.] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA.
[Andrews, Anne M.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA.
[Andrews, Anne M.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
[Boyden, Edward S.] MIT, Dept Biol Engn Brain & Cognit Sci, Media Lab, Cambridge, MA 02139 USA.
[Boyden, Edward S.] MIT, McGovern Inst, Cambridge, MA 02139 USA.
[Chun, Miyoung] Kavli Fdn, Oxnard, CA 93030 USA.
[Church, George M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Church, George M.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
[Church, George M.] Harvard Univ, Biophys Program, Boston, MA 02115 USA.
[Deisseroth, Karl; Schnitzer, Mark] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
[Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
[Deisseroth, Karl] Stanford Univ, Dept Psychiat, Stanford, CA 94305 USA.
[Donoghue, John P.] Brown Univ, Dept Comp Sci, Div Engn, Dept Neurosci, Providence, RI 02912 USA.
[Fraser, Scott E.; Park, Hongkun] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA.
[Fraser, Scott E.; Park, Hongkun] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
[Fraser, Scott E.; Park, Hongkun] Univ So Calif, Dept Physiol & Biophys, Los Angeles, CA 90089 USA.
[Fraser, Scott E.; Park, Hongkun] Univ So Calif, Dept Stem Cell Biol & Regenerat Med, Los Angeles, CA 90089 USA.
[Fraser, Scott E.; Park, Hongkun] Univ So Calif, Dept Pediat Radiol & Ophthalmol, Los Angeles, CA 90089 USA.
[Lippincott-Schwartz, Jennifer; Peterka, Darcy S.; Yuste, Rafael] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Looger, Loren L.] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
[Masmanidis, Sotiris] Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA.
[McEuen, Paul L.] Cornell Univ, Dept Phys, Lab Atom & Solid State Phys, Ithaca, NY 14853 USA.
[McEuen, Paul L.] Cornell Univ, Kavli Inst Cornell Nanoscale Sci, Ithaca, NY 14853 USA.
[Nurmikko, Arto V.] Brown Univ, Dept Phys, Providence, RI 02912 USA.
[Nurmikko, Arto V.] Brown Univ, Div Engn, Providence, RI 02912 USA.
[Fraser, Scott E.; Park, Hongkun] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
[Fraser, Scott E.; Park, Hongkun] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
[Lippincott-Schwartz, Jennifer; Peterka, Darcy S.; Yuste, Rafael] Columbia Univ, Howard Hughes Med Inst, New York, NY 10027 USA.
[Lippincott-Schwartz, Jennifer; Peterka, Darcy S.; Yuste, Rafael] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
[Reid, Clay] Allen Inst Brain Sci, Seattle, WA 98103 USA.
[Roukes, Michael L.; Scherer, Axel] CALTECH, Kavli Nanosci Inst, Pasadena, CA 91125 USA.
[Roukes, Michael L.; Scherer, Axel] CALTECH, Dept Phys, Pasadena, CA 91125 USA.
[Roukes, Michael L.; Scherer, Axel] CALTECH, Dept Appl Phys, Pasadena, CA 91125 USA.
[Roukes, Michael L.] CALTECH, Dept Bioengn, Pasadena, CA 91125 USA.
[Scherer, Axel] CALTECH, Dept Elect Engn, Pasadena, CA 91125 USA.
[Schnitzer, Mark] Stanford Univ, James H Clark Ctr, Dept Appl Phys, Stanford, CA 94305 USA.
[Schnitzer, Mark] Stanford Univ, James H Clark Ctr, Dept Biol, Stanford, CA 94305 USA.
[Sejnowski, Terrence J.] Salk Inst Biol Studies, Howard Hughes Med Inst, Computat Neurobiol Lab, La Jolla, CA 92037 USA.
[Sejnowski, Terrence J.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
[Shepard, Kenneth L.] Columbia Univ, Dept Elect Engn, New York, NY 10027 USA.
[Tsao, Doris] CALTECH, Div Biol, Pasadena, CA 91125 USA.
[Turrigiano, Gina] Brandeis Univ, Dept Biol, Waltham, MA 02254 USA.
[Turrigiano, Gina] Brandeis Univ, Ctr Complex Syst, Waltham, MA 02254 USA.
[Weiss, Paul S.] Univ Calif Los Angeles, Dept Mat Sci & Engn, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
[Xu, Chris] Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA.
[Yuste, Rafael] Columbia Univ, Kavli Inst Brain Sci, New York, NY 10027 USA.
[Zhuang, Xiaowei] Harvard Univ, Howard Hughes Med Inst, Dept Chem, Cambridge, MA 02138 USA.
[Zhuang, Xiaowei] Harvard Univ, Howard Hughes Med Inst, Dept Biol Chem, Cambridge, MA 02138 USA.
[Zhuang, Xiaowei] Harvard Univ, Howard Hughes Med Inst, Dept Phys, Cambridge, MA 02138 USA.
RP Masmanidis, S (reprint author), Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA.
EM smasmanidis@ucla.edu; etcher@caltech.edu; psw@cnsl.ucla.edu;
rmy5@columbia.edu
RI Andrews, Anne/B-4442-2011; Weiss, Paul/A-2575-2011; Alivisatos , Paul
/N-8863-2015
OI Andrews, Anne/0000-0002-1961-4833; Weiss, Paul/0000-0001-5527-6248;
Alivisatos , Paul /0000-0001-6895-9048
FU Kavli Foundation
FX We gratefully acknowledge the Kavli Foundation for support and
encouragement of this initiative and the discussions that led up to it.
The authors acknowledge helpful discussions with Prof. Adam Cohen, Dr.
Tim Harris, Prof. John Rogers, and Dr. Alan Rudolph, as well as many of
our colleagues. We thank Ms. Holly Bunje for help in preparing the
manuscript.
NR 179
TC 121
Z9 122
U1 13
U2 308
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1936-0851
EI 1936-086X
J9 ACS NANO
JI ACS Nano
PD MAR
PY 2013
VL 7
IS 3
BP 1850
EP 1866
DI 10.1021/nn4012847
PG 17
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA 115YB
UT WOS:000316846700005
PM 23514423
ER
PT J
AU Scheibye-Knudsen, M
Scheibye-Alsing, K
Canugovi, C
Croteau, DL
Bohr, VA
AF Scheibye-Knudsen, Morten
Scheibye-Alsing, Karsten
Canugovi, Chandrika
Croteau, Deborah L.
Bohr, Vilhelm A.
TI A novel diagnostic tool reveals mitochondrial pathology in human
diseases and aging
SO AGING-US
LA English
DT Article
DE aging; mitochondria; progeria; bioenergetics; diagnostics;
bioinformatics
ID DNA-DAMAGE; DYSFUNCTION; AGE; PREVALENCE; RESISTANCE; ATROPHY; CANCER;
BRAIN
AB The inherent complex and pleiotropic phenotype of mitochondrial diseases poses a significant diagnostic challenge for clinicians as well as an analytical barrier for scientists. To overcome these obstacles we compiled a novel database, www.mitodb.com, containing the clinical features of primary mitochondrial diseases. Based on this we developed a number of qualitative and quantitative measures, enabling us to determine whether a disorder can be characterized as mitochondrial. These included a clustering algorithm, a disease network, a mitochondrial barcode and two scoring algorithms. Using these tools we detected mitochondrial involvement in a number of diseases not previously recorded as mitochondrial. As a proof of principle Cockayne syndrome, ataxia with oculomotor apraxia 1 (AOA1), spinocerebellar ataxia with axonal neuropathy 1 (SCAN1) and ataxia-telangiectasia have recently been shown to have mitochondrial dysfunction and those diseases showed strong association with mitochondrial disorders. We next evaluated mitochondrial involvement in aging and detected two distinct categories of accelerated aging disorders, one of them being associated with mitochondrial dysfunction. Normal aging seemed to associate stronger with the mitochondrial diseases than the non-mitochondrial partially supporting a mitochondrial theory of aging.
C1 [Scheibye-Knudsen, Morten; Canugovi, Chandrika; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Bethesda, MD 20892 USA.
[Scheibye-Alsing, Karsten] Univ Copenhagen, Fac Hlth & Med Sci, IBHV, Sect Genet & Bioinformat, DK-1168 Copenhagen, Denmark.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Bethesda, MD 20892 USA.
EM vbohr@nih.gov
OI Scheibye-Knudsen, Morten/0000-0002-6637-1280
FU intramural program of the National Institutes of Health
FX We would like to thank Dr. Peter Sykora for critically reading the
manuscript. This work was supported by funds from the intramural program
of the National Institutes of Health.
NR 39
TC 19
Z9 19
U1 0
U2 6
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD MAR
PY 2013
VL 5
IS 3
BP 192
EP 208
PG 17
WC Cell Biology
SC Cell Biology
GA 116DO
UT WOS:000316863000007
PM 23524341
ER
PT J
AU Gourh, PR
Tan, FK
Rueda, B
Arnett, FC
Assassi, S
Reveille, JD
Radstake, TRD
Agarwal, SK
Martin, J
Mayes, MD
AF Gourh, Pravitt R.
Tan, Filemon K.
Rueda, Blanca
Arnett, Frank C.
Assassi, Shervin
Reveille, John D.
Radstake, Timothy R. D.
Agarwal, Sandeep K.
Martin, Javier
Mayes, Maureen D.
TI GENE-GENE INTERACTIONS IN INTERFERON PATHWAY GENE POLYMORPHISMS IN
EUROPEAN AND AMERICAN SCLERODERMA COHORTS
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Meeting Abstract
CT 33rd European Workshop for Rheumatology Research (EWRR)
CY FEB 28-MAR 02, 2013
CL Prague, CZECH REPUBLIC
SP UCB, Abbott, GlaxoSmithKline (GSK), MSD, AMGEN, MD Biosciences, Novo Nordisk
C1 [Gourh, Pravitt R.] NIH, Bethesda, MD 20892 USA.
[Tan, Filemon K.; Arnett, Frank C.; Assassi, Shervin; Reveille, John D.; Agarwal, Sandeep K.; Mayes, Maureen D.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[Rueda, Blanca] Univ Granada, Fac Ciencias Salud, Granada, Spain.
[Radstake, Timothy R. D.] Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Martin, Javier] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada, Spain.
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 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD MAR
PY 2013
VL 72
SU 1
BP A56
EP A57
PG 3
WC Rheumatology
SC Rheumatology
GA 115JM
UT WOS:000316808400144
ER
PT J
AU Mizesko, MC
Banerjee, PP
Monaco-Shawver, L
Mace, EM
Bernal, W
Sawalle-Belohradsky, J
Belohradsky, B
Heinz, V
Freeman, AF
Sullivan, KE
Holland, SM
Torgerson, TR
Al-Herz, W
Chou, J
Hanson, IC
Albert, MH
Geha, RS
Renner, ED
Orange, JS
AF Mizesko, M. C.
Banerjee, P. P.
Monaco-Shawver, L.
Mace, E. M.
Bernal, W.
Sawalle-Belohradsky, J.
Belohradsky, B.
Heinz, V.
Freeman, A. F.
Sullivan, K. E.
Holland, S. M.
Torgerson, T. R.
Al-Herz, W.
Chou, J.
Hanson, I. C.
Albert, M. H.
Geha, R. S.
Renner, E. D.
Orange, J. S.
TI IMPAIRED NATURAL KILLER CELL FUNCTION IN DOCK8 DEFICIENCY
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Meeting Abstract
CT 33rd European Workshop for Rheumatology Research (EWRR)
CY FEB 28-MAR 02, 2013
CL Prague, CZECH REPUBLIC
SP UCB, Abbott, GlaxoSmithKline (GSK), MSD, AMGEN, MD Biosciences, Novo Nordisk
C1 [Mizesko, M. C.; Banerjee, P. P.; Mace, E. M.; Hanson, I. C.; Orange, J. S.] Baylor Coll Med, Houston, TX 77030 USA.
[Mizesko, M. C.; Banerjee, P. P.; Mace, E. M.; Hanson, I. C.; Orange, J. S.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Monaco-Shawver, L.; Bernal, W.; Sullivan, K. E.] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA.
[Sawalle-Belohradsky, J.; Belohradsky, B.; Heinz, V.; Albert, M. H.; Renner, E. D.] Univ Munich, Univ Childrens Hosp, Munich, Germany.
[Freeman, A. F.; Holland, S. M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Torgerson, T. R.] Univ Washington, Seattle, WA 98195 USA.
[Torgerson, T. R.] Seattle Childrens Hosp, Seattle, WA USA.
[Al-Herz, W.] Kuwait Univ, Kuwait, Kuwait.
[Al-Herz, W.] Allergy & Clin Immunol Unit, Kuwait, Kuwait.
[Chou, J.; Geha, R. S.] Boston Childrens Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD MAR
PY 2013
VL 72
SU 1
BP A12
EP A13
DI 10.1136/annrheumdis-2013-203215.23
PG 3
WC Rheumatology
SC Rheumatology
GA 115JM
UT WOS:000316808400033
ER
PT J
AU Zou, BB
Li, QQ
Zhao, JS
Li, JM
Cuff, CF
Reed, E
AF Zou, Baobo
Li, Q. Quentin
Zhao, Jinshun
Li, Jueli M.
Cuff, Christopher F.
Reed, Eddie
TI beta-Elemene and Taxanes Synergistically Induce Cytotoxicity and Inhibit
Proliferation in Ovarian Cancer and Other Tumor Cells
SO ANTICANCER RESEARCH
LA English
DT Article
DE Chinese medicine; beta-elemene; taxanes; synergism; ovarian cancer;
prostate cancer; apoptosis; cell cycle arrest
ID IN-VITRO; PROSTATE-CANCER; BREAST-CANCER; ANTITUMOR-ACTIVITY; CARCINOMA
CELLS; STAGE-III; TAXOL; CHEMOTHERAPY; PACLITAXEL; APOPTOSIS
AB beta-Elemene, originally derived from plants, has been recently investigated as a new anticancer agent. The purpose of this study was to explore the efficacy and mechanisms of action of the combined use of beta-elemene plus a taxane as an antitumor therapeutic strategy for ovarian cancer and other carcinomas. The interaction of beta-elemene with paclitaxel or docetaxel produced additive to moderately synergistic effects against the platinum-resistant ovarian cancer cell line A2780/CP70 and its parental cell line A2780, and showed moderately synergistic activity against PC-3 prostate cancer cells. In addition, the co-administration of beta-elemene and a taxane at low-micromolar concentrations dramatically increased the rate of micronucleus formation and the percentage of mitotic arrest in both ovarian cancer cell lines, as compared with treatment with either agent alone. The highest synergy towards the ovarian cancer cells was observed with beta-elemene plus docetaxel. Consistent with these data, treatment of A2780/CP70 cells with 16-elemene plus a taxane strikingly reduced cell viability and increased cell apoptosis, as assessed by annexin V binding. Moreover, beta-elemene plus docetaxel induced elevated levels of caspase-9 and p53 proteins in A2780/CP70 cells, and the combination of beta-elemene plus a taxane caused marked cell-cycle arrest at the G(2)/M phase in these cells. One possible mechanism to account for the enhanced cytotoxic efficacy of this combination treatment is a beta-elemene-induced increase in taxane influx into cancer cells. These observations indicate that combination therapy with beta-elemene and taxanes has synergistic antitumor activity against ovarian and prostate carcinomas in vitro. This promising new therapeutic combination warrants further pre-clinical exploration for the treatment of chemoresistant ovarian cancer and other types of tumors.
C1 [Zou, Baobo; Zhao, Jinshun] Ningbo Univ, Sch Med, Dept Publ Hlth, Zhejiang Prov Key Lab Pathol & Physiol Technol, Ningbo 315211, Zhejiang, Peoples R China.
[Zou, Baobo; Li, Q. Quentin; Zhao, Jinshun; Cuff, Christopher F.; Reed, Eddie] W Virginia Univ, Sch Med, Morgantown, WV 26506 USA.
[Li, Jueli M.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA.
[Li, Q. Quentin; Reed, Eddie] NCI, NIH, Bethesda, MD 20892 USA.
RP Li, QQ (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM liquenti@mail.nih.gov
FU National Nature Science Foundation of China [81273111]; Foundation of
Innovative Research Team of Educational Commission of Zhejiang Province
[T200907]; Nature Science Foundation of Ningbo City [2012A610185];
Ningbo Scientific Projects [2012C5019, SZX11073]; Scientific Innovation
Team Project of Ningbo [2011B82014]; Innovative Research Team of Ningbo
[2009B21002]; Ningbo University; U.S. National Institutes of Health
[P20RR16440-010003, P20RR16440-020003, P20RR16440-030003,
P20RR16440-040003]; West Virginia University School of Medicine Research
Grant
FX This publication was made possible by grants from the National Nature
Science Foundation of China (no. 81273111), the Foundation of Innovative
Research Team of Educational Commission of Zhejiang Province (T200907),
the Nature Science Foundation of Ningbo City (no. 2012A610185), the
Ningbo Scientific Projects (2012C5019 and SZX11073), the Scientific
Innovation Team Project of Ningbo (no. 2011B82014), Innovative Research
Team of Ningbo (2009B21002) and K.C. Wong Magna Fund in Ningbo
University, and by grants from the U.S. National Institutes of Health
(nos. P20RR16440-010003, P20RR16440-020003, P20RR16440-030003,
P20RR16440-040003) and a West Virginia University School of Medicine
Research Grant (to QQL).
NR 59
TC 8
Z9 8
U1 1
U2 6
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
J9 ANTICANCER RES
JI Anticancer Res.
PD MAR
PY 2013
VL 33
IS 3
BP 929
EP 940
PG 12
WC Oncology
SC Oncology
GA 114VH
UT WOS:000316770400024
PM 23482764
ER
PT J
AU Mastelic, B
Lewis, DJM
Golding, H
Gust, I
Sheets, R
Lambert, PH
AF Mastelic, Beatris
Lewis, David J. M.
Golding, Hana
Gust, Ian
Sheets, Rebecca
Lambert, Paul-Henri
TI Potential use of inflammation and early immunological event biomarkers
in assessing vaccine safety
SO BIOLOGICALS
LA English
DT Article
DE Vaccine; Biomarkers; Vaccine safety
ID MONOCYTE ACTIVATION TEST; HUMAN SERUM-ALBUMIN; WHOLE-BLOOD ASSAY;
IN-WATER EMULSION; CD4(+) T-CELLS; NALP3 INFLAMMASOME; DENDRITIC CELLS;
INTERNATIONAL VALIDATION; BYSTANDER ACTIVATION; AUTOIMMUNE-DISEASES
AB Highly effective vaccines have traditionally been designed in a rather empirical way, often with incomplete understanding of their mode of action. Full assessment of efficacy and reactogenicity takes time and, as a result, vaccine introduction to the market is usually slow and expensive. In addition, in rare cases, unacceptable reactogenicity may only become apparent after years of development or even widespread use. However, recent advances in cell biology and immunology offer a range of new technologies and systems for identifying biological responses or "biomarkers" that could possibly be used to evaluate and predict efficacy and safety during vaccine development and post-marketing surveillance. This report reflects the conclusions of a group of scientists from academia, regulatory agencies and industry who attended a conference on the potential use of biomarkers to assess vaccine safety which was held in Baltimore, Maryland, USA, from 10 to 11 May 2012 and organized by the International Association for Biologicals (JABS). The conference focused particularly on determining which biomarkers might relate to vaccine efficacy and reactogenicity and whether our knowledge base was sufficiently robust at this time for the data to be used for decision-making. More information on the conference output can be found on the JABS website, http://www.iabs.org/.
C1 [Mastelic, Beatris; Lambert, Paul-Henri] Univ Geneva, WHO, Ctr Vaccinol & Neonatal Immunol, CMU, CH-1211 Geneva 4, Switzerland.
[Lewis, David J. M.] Univ Surrey, Clin Res Ctr, Guildford GU2 7XP, Surrey, England.
[Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA.
[Gust, Ian] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
[Sheets, Rebecca] NIAID, CAPT, US PHS, NIH, Bethesda, MD 20892 USA.
RP Lambert, PH (reprint author), Univ Geneva, WHO, Ctr Vaccinol & Neonatal Immunol, CMU, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland.
EM paul.lambert@unige.ch
OI Lewis, David JM/0000-0003-3105-9075
FU GlaxoSmithKline Biologicals; Sanofi Pasteur; Novartis; IMI; Pfizer; CSL
FX We thank Betty Dodet (Dodet Bioscience) for her skillful help in the
preparation of this report. This workshop was made possible by
unrestricted educational grants from GlaxoSmithKline Biologicals, Sanofi
Pasteur, Novartis, IMI, Pfizer and CSL.
NR 72
TC 8
Z9 8
U1 1
U2 10
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1045-1056
J9 BIOLOGICALS
JI Biologicals
PD MAR
PY 2013
VL 41
IS 2
BP 115
EP 124
DI 10.1016/j.biologicals.2012.10.005
PG 10
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
GA 115WX
UT WOS:000316843700010
PM 23194656
ER
PT J
AU Reina, SA
Shomaker, LB
Mooreville, M
Courville, AB
Brady, SM
Olsen, C
Yanovski, SZ
Tanofsky-Kraff, M
Yanovski, JA
AF Reina, Samantha A.
Shomaker, Lauren B.
Mooreville, Mira
Courville, Amber B.
Brady, Sheila M.
Olsen, Cara
Yanovski, Susan Z.
Tanofsky-Kraff, Marian
Yanovski, Jack A.
TI Sociocultural pressures and adolescent eating in the absence of hunger
SO BODY IMAGE
LA English
DT Article
DE Body image; Adolescence; Eating in the absence of hunger; Pressure to be
thin; Obesity
ID CHILD-FEEDING QUESTIONNAIRE; BODY-IMAGE; ENERGY-INTAKE; DIETARY
RESTRAINT; PUBERTAL CHANGES; COLLEGE-WOMEN; RISK-FACTORS; ACUTE STRESS;
WEIGHT-GAIN; OVERWEIGHT
AB Parental feeding practices and sociocultural pressures theoretically influence eating behavior. Yet, whether these factors relate to eating in the absence of hunger (EAH) is unknown. We assessed if sociocultural pressures were associated with EAH among 90 adolescents (M-age = 15.27, SD = 1.39; 48% female). Parents completed the Child Feeding Questionnaire. Adolescents completed the Perceived Sociocultural Pressures Scale, Sociocultural Attitudes Towards Appearance Questionnaire-3, and Multidimensional Body Self-Relations Questionnaire-Appearance Scales. On two occasions, EAH was assessed as snack food intake after adolescents ate to satiety. Controlling for body composition and demographics, parental restriction and family pressure to be thin were associated with greater EAH. Media pressure was related to more EAH in girls. Appearance orientation and preoccupation with becoming overweight mediated links between sociocultural pressures and EAH. Findings support the notion that sociocultural pressures and their links to body image may contribute to the course of disinhibited eating behaviors during adolescence. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Reina, Samantha A.; Shomaker, Lauren B.; Mooreville, Mira; Brady, Sheila M.; Yanovski, Susan Z.; Tanofsky-Kraff, Marian; Yanovski, Jack A.] Natl Inst Child Hlth & Human Dev NICHD, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
[Shomaker, Lauren B.; Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol MPS, Bethesda, MD 20814 USA.
[Courville, Amber B.] NIH, Dept Nutr, Ctr Clin, Bethesda, MD 20892 USA.
[Olsen, Cara] USUHS, Dept Prevent Med & Biometr, Bethesda, MD USA.
[Yanovski, Susan Z.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD USA.
RP Shomaker, LB (reprint author), NICHHD, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH CRC, 10 Ctr Dr,MSC 1103,Room 1-3330, Bethesda, MD 20892 USA.
EM shomakel@mail.nih.gov
OI Yanovski, Jack/0000-0001-8542-1637
FU Intramural NIH HHS [Z99 HD999999, ZIA HD000641-17]; NICHD NIH HHS
[1F32HD056762, 1K99HD069516, F32 HD056762, K99 HD069516, Z01 HD000641,
Z01HD00641]
NR 81
TC 2
Z9 2
U1 4
U2 36
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1740-1445
J9 BODY IMAGE
JI Body Image
PD MAR
PY 2013
VL 10
IS 2
BP 182
EP 190
DI 10.1016/j.bodyim.2012.12.004
PG 9
WC Psychology, Clinical; Psychiatry; Psychology, Multidisciplinary
SC Psychology; Psychiatry
GA 118LM
UT WOS:000317027000005
PM 23394966
ER
PT J
AU Zamarin, D
Giralt, S
Landau, H
Lendvai, N
Lesokhin, A
Chung, D
Koehne, G
Chimento, D
Devlin, SM
Riedel, E
Bhutani, M
Babu, D
Hassoun, H
AF Zamarin, D.
Giralt, S.
Landau, H.
Lendvai, N.
Lesokhin, A.
Chung, D.
Koehne, G.
Chimento, D.
Devlin, S. M.
Riedel, E.
Bhutani, M.
Babu, D.
Hassoun, H.
TI Patterns of relapse and progression in multiple myeloma patients after
auto-SCT: implications for patients' monitoring after transplantation
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE multiple myeloma; autologous transplantation; relapse; free light chain
assay
ID FREE LIGHT-CHAIN; STEM-CELL TRANSPLANTATION; MONOCLONAL GAMMOPATHIES;
SERUM; IMMUNOGLOBULIN; URINE; IMMUNOFIXATION
AB Auto-SCT (ASCT) is widely used in first-line treatment of multiple myeloma (MM). However, most patients eventually relapse or have progression of disease (R/POD). Although precise knowledge of R/POD patterns would be important to generate evidence-based surveillance recommendations after ASCT, such data is limited in the literature, especially after introduction of the free light chain assay (FLCA). This retrospective study examined the patterns of R/POD after first-line ASCT in 273 patients, using established criteria. At the time of R/POD, only 2% of patients had no associated serological evidence of R/POD. A total of 85% had asymptomatic R/POD, first detected by serological testing, whereas 15% had symptomatic R/POD with aggressive disease, early R/POD and short survival, with poor cytogenetics and younger age identified as risk factors. Although occult skeletal lesions were found in 40% of asymptomatic patients tested following serological R/POD, yearly skeletal surveys and urine testing were poor at heralding R/POD. We found a consistent association between paraprotein types at diagnosis and R/POD, allowing informed recommendations for appropriate serological monitoring and propose a new needed criterion using FLCA for patients relapsing by FLC only. Our findings provide important evidence-based recommendations that strengthen current monitoring guidelines after first-line ASCT in MM. Bone Marrow Transplantation (2013) 48, 419-424; doi:10.1038/bmt.2012.151; published online 13 August 2012
C1 [Zamarin, D.; Giralt, S.; Landau, H.; Lendvai, N.; Lesokhin, A.; Chung, D.; Koehne, G.; Chimento, D.; Hassoun, H.] Mem Sloan Kettering Canc Ctr, Dept Med, Div Hematol Malignancies, New York, NY 10065 USA.
[Devlin, S. M.; Riedel, E.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA.
[Bhutani, M.] NCI, Dept Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Babu, D.] Columbia Univ Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, Mem Sloan Kettering Canc Ctr, Dept Internal Med, New York, NY 10032 USA.
[Babu, D.] Weil Cornell Med Sch, New York, NY USA.
RP Hassoun, H (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Div Hematol Malignancies, 1275 York Ave,Room H709, New York, NY 10065 USA.
EM hassounh@mskcc.org
FU NCI NIH HHS [T32 CA009207]
NR 27
TC 12
Z9 12
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD MAR
PY 2013
VL 48
IS 3
BP 419
EP 424
DI 10.1038/bmt.2012.151
PG 6
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 116YU
UT WOS:000316920100016
PM 22890289
ER
PT J
AU Liu, W
Liu, Y
Guo, T
Hu, C
Luo, H
Zhang, L
Shi, S
Cai, T
Ding, Y
Jin, Y
AF Liu, W.
Liu, Y.
Guo, T.
Hu, C.
Luo, H.
Zhang, L.
Shi, S.
Cai, T.
Ding, Y.
Jin, Y.
TI TCF3, a novel positive regulator of osteogenesis, plays a crucial role
in miR-17 modulating the diverse effect of canonical Wnt signaling in
different microenvironments
SO CELL DEATH & DISEASE
LA English
DT Article
DE transcription factor 3; miR-17; canonical Wnt signaling; osteogenesis;
microenvironment
ID MESENCHYMAL STEM-CELLS; BONE-MARROW MICROENVIRONMENT; HUMAN
PERIODONTAL-LIGAMENT; GENE-EXPRESSION; LINEAGE COMMITMENT; SELF-RENEWAL;
IN-VIVO; RUNX2; PROLIFERATION; OSTEOBLASTS
AB Wnt signaling pathways are a highly conserved pathway, which plays an important role from the embryonic development to bone formation. The effect of Wnt pathway on osteogenesis relies on their cellular environment and the expression of target genes. However, the molecular mechanism of that remains unclear. On the basis of the preliminary results, we observed the contrary effect of canonical Wnt signaling on osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in the different culture environment. Furthermore, we found that the expression level of miR-17 was also varied with the change in the culture environment. Therefore, we hypothesized that miR-17 and canonical Wnt signaling may have potential interactions, particularly the inner regulation relationship in different microenvironments. In this paper, we observed that canonical Wnt signaling promoted osteogenesis of PDLSCs in the fully culture medium, while inhibited it in the osteogenic differentiation medium. Interestingly, alteration in the expression level of endogenous miR-17 could partially reverse the different effect of canonical Wnt signaling. Furthermore, the role of miR-17 was because of its target gene TCF3 (transcription factor 3), a key transcription factor of canonical Wnt pathway. Overexpression of TCF3 attenuated the effect of miR-17 on modulating canonical Wnt signaling. Finally, we elucidated that TCF3 enhanced osteogenesis both in vitro and in vivo. In brief, the different level of miR-17 was the main cause of the different effect of canonical Wnt signaling, and TCF3 was the crucial node of miR-17-canonial Wnt signaling regulation loop. This understanding of microRNAs regulating signaling pathways in different microenvironments may pave the way for fine-tuning the process of osteogenesis in bone-related disorders. Cell Death and Disease (2013) 4, e539; doi:10.1038/cddis.2013.65; published online 14 March 2013
C1 [Liu, W.; Liu, Y.; Guo, T.; Ding, Y.] Fourth Mil Med Univ, Sch Stomatol, Dept Orthodont, Xian 710032, Shaanxi, Peoples R China.
[Liu, W.; Liu, Y.; Hu, C.; Luo, H.; Zhang, L.; Jin, Y.] Fourth Mil Med Univ, Res & Dev Ctr Tissue Engn, Xian 710032, Shaanxi, Peoples R China.
[Shi, S.] Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90089 USA.
[Cai, T.] NIDCR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD USA.
[Jin, Y.] Fourth Mil Med Univ, Dept Oral Histol & Pathol, Sch Stomatol, Xian 710032, Shaanxi, Peoples R China.
RP Jin, Y (reprint author), 145 West Changle Rd, Xian 710032, Shaanxi, Peoples R China.
EM Dingyin@fmmu.edu.cn; yanjin@fmmu.edu.cn
RI Hu, Cheng-Hu/I-4210-2013; Jin, Yan/I-4204-2013
FU National Basic Research Program (973 Program) [2011CB964700,
2010CB944802]; Nature Science Foundation of China [81020108019,
31030033, 31200972]; National Institute of Dental and Craniofacial
Research, National Institutes of Health; Department of Health and Human
Services [R01DE019932]
FX This work was supported by grants from the National Basic Research
Program (973 Program) (2011CB964700 and 2010CB944802), the Nature
Science Foundation of China (81020108019, 31030033 and 31200972) and a
grant from the National Institute of Dental and Craniofacial Research,
National Institutes of Health and Department of Health and Human
Services (R01DE019932 to SS).
NR 47
TC 15
Z9 17
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD MAR
PY 2013
VL 4
AR e539
DI 10.1038/cddis.2013.65
PG 11
WC Cell Biology
SC Cell Biology
GA 116FR
UT WOS:000316868700018
PM 23492770
ER
PT J
AU Liu, J
Nussinov, R
AF Liu, Jin
Nussinov, Ruth
TI The role of allostery in the ubiquitin-proteasome system
SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Review
DE Allosteric; allostery; degradation; molecular machine; ubiquitin
ID END RULE PATHWAY; CONJUGATING ENZYME; STRUCTURAL BASIS; DRUG DISCOVERY;
SACCHAROMYCES-CEREVISIAE; MULTIUBIQUITIN CHAIN; MECHANISTIC INSIGHTS;
SUMO CONJUGATION; BINDING CASCADES; FOLDING FUNNELS
AB The ubiquitin-proteasome system (UPS) is involved in many cellular processes including protein degradation. Degradation of a protein via this system involves two successive steps: ubiquitination and degradation. Ubiquitination tags the target protein with ubiquitin-like proteins (UBLs), such as ubiquitin, small ubiquitin-like modifier (SUMO) and NEDD8, via a cascade involving three enzymes: activating enzyme E1, conjugating enzyme E2 and E3 ubiquitin ligases. The proteasomes recognize the UBL-tagged substrate proteins and degrade them. Accumulating evidence indicates that allostery is a central player in the regulation of ubiquitination, as well as deubiquitination and degradation. Here, we provide an overview of the key mechanistic roles played by allostery in all steps of these processes, and highlight allosteric drugs targeting them. Throughout the review, we emphasize the crucial mechanistic role played by linkers in allosterically controlling the UPS action by biasing the sampling of the conformational space, which facilitate the catalytic reactions of the ubiquitination and degradation. Finally, we propose that allostery may similarly play key roles in the regulation of molecular machines in the cell, and as such allosteric drugs can be expected to be increasingly exploited in therapeutic regimes.
C1 [Liu, Jin; Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program,Frederick Natl Lab, Frederick, MD 21701 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
EM NussinoR@helix.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 number HHSN261200800001E. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does the mention of trade names,
commercial products or organizations imply endorsement by the U.S.
Government. This research was supported (in part) by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.
NR 89
TC 16
Z9 18
U1 0
U2 15
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1040-9238
J9 CRIT REV BIOCHEM MOL
JI Crit. Rev. Biochem. Mol. Biol.
PD MAR-APR
PY 2013
VL 48
IS 2
BP 89
EP 97
DI 10.3109/10409238.2012.742856
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 117LN
UT WOS:000316955000001
PM 23234564
ER
PT J
AU Marullo, L
Dupuis, J
Scapoli, C
Meigs, JB
Morris, A
Prokopenko, I
AF Marullo, L.
Dupuis, J.
Scapoli, C.
Meigs, J. B.
Morris, A.
Prokopenko, I.
TI Impact of Type 2 diabetes susceptibility loci on variation in multiple
cardio-metabolic traits
SO DIABETIC MEDICINE
LA English
DT Meeting Abstract
C1 [Marullo, L.; Scapoli, C.] Univ Ferrara, Dept Life Sci & Biotechnol, I-44100 Ferrara, Italy.
[Marullo, L.; Morris, A.; Prokopenko, I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Dupuis, J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Dupuis, J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Meigs, J. B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Meigs, J. B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Prokopenko, I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
RI Scapoli, Chiara/E-2268-2015
OI Scapoli, Chiara/0000-0003-4058-4787
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0742-3071
J9 DIABETIC MED
JI Diabetic Med.
PD MAR
PY 2013
VL 30
SU 1
SI SI
BP 51
EP 51
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 108AQ
UT WOS:000316263400161
ER
PT J
AU Fliedner, SM
Shankavaram, U
Elkahloun, AG
Huynh, TT
Linehan, WM
Timmers, HJ
Tischler, AS
Powers, J
de Krijger, R
Baysal, B
David, G
Lehnert, H
Camphausen, K
Pacak, K
AF Fliedner, S. M.
Shankavaram, U.
Elkahloun, A. G.
Huynh, T. T.
Linehan, W. M.
Timmers, H. J.
Tischler, A. S.
Powers, J.
de Krijger, R.
Baysal, B.
David, G.
Lehnert, H.
Camphausen, K.
Pacak, K.
TI Genotype and tumor location determine gene expression signatures in
pseudohypoxic pheochromocytomas and paragangliomas
SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES
LA English
DT Meeting Abstract
C1 [Fliedner, S. M.; Lehnert, H.] Univ Hosp Schleswig Holstein, Dept Med 1, Lubeck, Germany.
[Fliedner, S. M.; Huynh, T. T.; Pacak, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
[Shankavaram, U.; David, G.; Camphausen, K.] NCI, NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Elkahloun, A. G.] NHGRI, NIH, Canc Genet Branch, Bethesda, MD 20892 USA.
[Linehan, W. M.] NCI, NIH, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Timmers, H. J.] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands.
[Tischler, A. S.; Powers, J.] Tufts Med Ctr, Dept Pathol, Boston, MA USA.
[de Krijger, R.] Erasmus MC Univ, Med Ctr, Dept Pathol, Josephine Nefkens Inst, Rotterdam, Netherlands.
[Baysal, B.] Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA.
[David, G.] Feinberg Northwestern Med Sch, Dept Radiat Oncol, Chicago, IL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH
PI STUTTGART
PA RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0947-7349
J9 EXP CLIN ENDOCR DIAB
JI Exp. Clin. Endocrinol. Diabet.
PD MAR
PY 2013
VL 121
IS 3
MA P27
DI 10.1055/s-0033-1336697
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 113IE
UT WOS:000316659000092
ER
PT J
AU Pamporaki, C
Darr, R
Bursztyn, M
Krinner, A
Glokner, S
Bornstein, S
Pacak, K
Lenders, JWM
Eisenhofer, G
AF Pamporaki, C.
Daerr, R.
Bursztyn, M.
Krinner, A.
Gloekner, S.
Bornstein, S.
Pacak, K.
Lenders, J. W. M.
Eisenhofer, G.
TI Plasma free versus deconjugated metanephrines for diagnosis of
pheochromocytoma
SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES
LA English
DT Meeting Abstract
C1 [Pamporaki, C.; Daerr, R.; Gloekner, S.; Eisenhofer, G.] Uniklinikum Dresden, Inst Clin Chem & Lab Med, Dresden, Germany.
[Bursztyn, M.; Bornstein, S.] Uniklinikum Dresden, Dresden, Germany.
[Krinner, A.] Tech Univ Dresden, Inst Med Informat & Biometry, Dresden, Germany.
[Pacak, K.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Lenders, J. W. M.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
RI Lenders, J.W.M./L-4487-2015
NR 0
TC 0
Z9 0
U1 0
U2 2
PU JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH
PI STUTTGART
PA RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0947-7349
J9 EXP CLIN ENDOCR DIAB
JI Exp. Clin. Endocrinol. Diabet.
PD MAR
PY 2013
VL 121
IS 3
MA OP2_13
DI 10.1055/s-0033-1336621
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 113IE
UT WOS:000316659000014
ER
PT J
AU Yamane, H
Paul, WE
AF Yamane, Hidehiro
Paul, William E.
TI Early signaling events that underlie fate decisions of naive CD4(+) T
cells toward distinct T-helper cell subsets
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE T-helper cells; TCR signals; cytokines; transcription factors; Notch
pathway
ID NF-KAPPA-B; TGF-BETA; IN-VIVO; GATA3 EXPRESSION; MICE LACKING; T(H)2
DIFFERENTIATION; TH2 DIFFERENTIATION; MEDIATED ACTIVATION; CYTOKINE
PRODUCTION; KINASE ACTIVATION
AB CD4(+) T-helper (Th) cells are a major cell population that play an important role in governing acquired immune responses to a variety of foreign antigens as well as inducing some types of autoimmune diseases. There are at least four distinct Th cell subsets (Th1, Th2, Th17, and inducible T-regulatory cells), each of which has specialized functions to control immune responses. Each of these cell types emerge from naive CD4(+) T cells after encounter with foreign antigens presented by dendritic cells (DCs). Each Th cell subset expresses a unique set of transcription factors and produces hallmark cytokines. Both T-cell receptor (TCR)-mediated stimulation and the cytokine environment created by activated CD4(+) T cells themselves, by 'partner' DCs, and/or other cell types during the course of differentiation, play an important role in the fate decisions toward distinct Th subsets. Here, we review how TCR-mediated signals in collaboration with the cytokine environment influence the fate decisions of naive CD4(+) T cells toward distinct Th subsets at the early stages of activation. We also discuss the roles of TCR-proximal signaling intermediates and of the Notch pathway in regulating the differentiation to distinct Th phenotypes.
C1 [Yamane, Hidehiro; Paul, William E.] NIAID, Cytokine Biol Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Yamane, H (reprint author), Bldg 10,Room 11N314,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hyamane@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, USA
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, USA. The authors declare no competing financial interests.
NR 99
TC 119
Z9 119
U1 3
U2 47
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD MAR
PY 2013
VL 252
SI SI
BP 12
EP 23
DI 10.1111/imr.12032
PG 12
WC Immunology
SC Immunology
GA 119DT
UT WOS:000317078300002
PM 23405892
ER
PT J
AU Vahedi, G
Poholek, AC
Hand, TW
Laurence, A
Kanno, Y
O'Shea, JJ
Hirahara, K
AF Vahedi, Golnaz
Poholek, Amanda C.
Hand, Timothy W.
Laurence, Arian
Kanno, Yuka
O'Shea, John J.
Hirahara, Kiyoshi
TI Helper T-cell identity and evolution of differential transcriptomes and
epigenomes
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE T-cell plasticity; STAT; epigenetics; histone modification; T-cell
differentiation; enhancers; master regulator
ID DE-NOVO DIFFERENTIATION; IFN-GAMMA PROMOTER; HYPER-IGE SYNDROME;
IN-VIVO; GENE-EXPRESSION; TH17 CELLS; MOLECULAR-MECHANISMS; TH2
DIFFERENTIATION; LINEAGE COMMITMENT; EPIGENETIC CONTROL
AB CD4(+) T cells are critical for the elimination of an immense array of microbial pathogens. Among the ways they accomplish this task is to generate progeny with specialized, characteristic patterns of gene expression. From this perspective, helper cells can be viewed as pluripotent precursors that adopt distinct cell fates. Although there are aspects of helper cell differentiation that can be modeled as a classic cell fate commitment, CD4(+) T cells also maintain considerable flexibility in their transcriptional program. This makes sense in terms of host defense, but raises the question of how these remarkable cells balance both these requirements, a high degree of specific gene expression and the capacity for plasticity. In this review, we discuss recent advances in our understanding of CD4(+) T-cell specification, focusing on how genomic perspectives have influenced our views of these processes. 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 are considered as they relate to the helper cell transcriptome and epigenome.
C1 [Vahedi, Golnaz; Poholek, Amanda C.; Laurence, Arian; Kanno, Yuka; O'Shea, John J.; Hirahara, Kiyoshi] NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA.
[Hand, Timothy W.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP O'Shea, JJ (reprint author), 10 Ctr Dr,Bldg10,Room 13C103, Bethesda, MD 20892 USA.
EM osheajo@mail.nih.gov
RI Kanno, Yuka/B-5802-2013; Laurence, Arian/A-8770-2009; Hirahara,
Kiyoshi/E-2460-2017;
OI Laurence, Arian/0000-0003-0942-8292; Hirahara,
Kiyoshi/0000-0002-9128-9449; Kanno, Yuka/0000-0001-5668-9319
FU NIH/NIAMS Intramural Research Program (IRP); JSPS; PRAT
FX This work was supported by NIH/NIAMS Intramural Research Program (IRP),
the JSPS Research Fellowship for Japanese Biomedical and Behavioral
Researchers at NIH (K. H.) and PRAT (A. P.). The authors have no
conflicts of interest to declare.
NR 218
TC 46
Z9 48
U1 1
U2 22
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
EI 1600-065X
J9 IMMUNOL REV
JI Immunol. Rev.
PD MAR
PY 2013
VL 252
SI SI
BP 24
EP 40
DI 10.1111/imr.12037
PG 17
WC Immunology
SC Immunology
GA 119DT
UT WOS:000317078300003
PM 23405893
ER
PT J
AU Boyer, CB
Hightow-Weidman, L
Bethel, J
Li, SX
Henry-Reid, L
Futterman, D
Maturo, D
Straub, DM
Howell, K
Reid, S
Lowe, J
Kapogiannis, BG
Ellen, JM
AF Boyer, Cherrie B.
Hightow-Weidman, Lisa
Bethel, James
Li, Su X.
Henry-Reid, Lisa
Futterman, Donna
Maturo, Donna
Straub, Diane M.
Howell, Kourtney
Reid, Shirleta
Lowe, Jaime
Kapogiannis, Bill G.
Ellen, Jonathan M.
TI An Assessment of the Feasibility and Acceptability of a Friendship-Based
Social Network Recruitment Strategy to Screen At-Risk African American
and Hispanic/Latina Young Women for HIV Infection
SO JAMA PEDIATRICS
LA English
DT Article
ID UNITED-STATES; PROJECT ORE; ADOLESCENTS; YOUTH; INTERVENTION;
POPULATIONS; HIV/STI; RATES; MEN
AB Objectives: To examine the feasibility and acceptability of a friendship-based network recruitment strategy for identifying undiagnosed human immunodeficiency virus (HIV) infection within young women's same-sex friendship networks and to determine factors that facilitated and hindered index recruiters (IRs) in recruiting female friendship network members (FNMs) as well as factors that facilitated and hindered FNMs in undergoing HIV screening.
Design: A cross-sectional study design that incorporated dual incentives for IRs and their female FNMs.
Setting: The IRs were recruited through 3 Adolescent Trials Network for HIV/AIDS Interventions sites within their Adolescent Medicine Trials Units. Data were collected from January 1, 2009, through June 30, 2010.
Participants: The IRs self-identifying as HIV positive, negative, or status unknown were enrolled to recruit FNMs to undergo HIV screening.
Main Outcome Measures: Self-reports of HIV risk and facilitators and barriers to network recruitment and HIV screening were assessed using an audio-computer-assisted self-interview. Participants were identified as HIV negative or positive on the basis of an OraQuick HIV test with confirmatory enzyme-linked immunosorbent assay and/or Western blot tests.
Results: Nearly all (156 [98.1%]) eligible IRs agreed to participate and most (78.4%) recruited 1 or more FNMs. Of the 381 FNMs, most (342 [89.8%]) agreed to HIV screening. Although a high acceptance of HIV screening was achieved, the HIV prevalence was low (0.26%).
Conclusion: Our findings provide compelling evidence to suggest that use of a female friendship network approach is a feasible and acceptable means for engaging at-risk young women in HIV screening, as shown by their high rates of agreement to undergo HIV screening. JAMA Pediatr.2013;167(3):289-296. Published online January 21, 2013. doi:10.1001/2013.jamapediatrics.398
C1 [Boyer, Cherrie B.] Univ Calif San Francisco, Div Adolescent & Young Adult Med, Dept Pediat, San Francisco, CA 94118 USA.
[Hightow-Weidman, Lisa] Univ N Carolina, Dept Med, Div Infect Dis, Chapel Hill, NC USA.
[Bethel, James; Li, Su X.] WESTAT Corp, Rockville, MD 20850 USA.
[Henry-Reid, Lisa; Lowe, Jaime] John H Stroger Jr Hosp Cook Cty, Div Adolescent & Young Adult Med, Dept Pediat, Chicago, IL USA.
[Futterman, Donna; Howell, Kourtney] Montefiore Med Ctr, Div Adolescent Med, Dept Pediat, Bronx, NY 10467 USA.
[Maturo, Donna; Reid, Shirleta] Univ Miami, Sch Med, Div Adolescent Med, Miami, FL USA.
[Straub, Diane M.] Univ S Florida, Div Gen Pediat & Adolescent Med, Tampa, FL USA.
[Kapogiannis, Bill G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat & Adolescent Med Branch, NIH, Bethesda, MD USA.
[Ellen, Jonathan M.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
RP Boyer, CB (reprint author), Univ Calif San Francisco, Div Adolescent & Young Adult Med, Dept Pediat, 3333 Calif St,Ste 245, San Francisco, CA 94118 USA.
EM boyerc@peds.ucsf.edu
FU National Institutes of Health through the National Institute of Child
Health and Human Development [U01 HD40533]; National Institute on Drug
Abuse; National Institute on Mental Health
FX The Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN)
is funded by grant U01 HD40533 from the National Institutes of Health
through the National Institute of Child Health and Human Development
with supplemental funding from the National Institute on Drug Abuse and
the National Institute on Mental Health.
NR 26
TC 3
Z9 3
U1 1
U2 10
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6203
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD MAR
PY 2013
VL 167
IS 3
BP 289
EP 296
DI 10.1001/2013.jamapediatrics.398
PG 8
WC Pediatrics
SC Pediatrics
GA 115GB
UT WOS:000316799500012
PM 23338776
ER
PT J
AU Guha, S
Rees, E
Darvasi, A
Ivanov, D
Ikeda, M
Bergen, SE
Magnusson, PK
Cormican, P
Morris, D
Gill, M
Cichon, S
Rosenfeld, JA
Lee, A
Gregersen, PK
Kane, JM
Malhotra, AK
Rietschel, M
Nothen, MM
Degenhardt, F
Priebe, L
Breuer, R
Strohmaier, J
Ruderfer, DM
Moran, JL
Chambert, KD
Sanders, AR
Shi, JX
Kendler, K
Riley, B
O'Neill, T
Walsh, D
Malhotra, D
Corvin, A
Purcell, S
Sklar, P
Iwata, N
Hultman, CM
Sullivan, PF
Sebat, J
McCarthy, S
Gejman, PV
Levinson, DF
Owen, MJ
O'Donovan, MC
Lencz, T
Kirov, G
AF Guha, Saurav
Rees, Elliott
Darvasi, Ariel
Ivanov, Dobril
Ikeda, Masashi
Bergen, Sarah E.
Magnusson, Patrik K.
Cormican, Paul
Morris, Derek
Gill, Michael
Cichon, Sven
Rosenfeld, Jeffrey A.
Lee, Annette
Gregersen, Peter K.
Kane, John M.
Malhotra, Anil K.
Rietschel, Marcella
Noethen, Markus M.
Degenhardt, Franziska
Priebe, Lutz
Breuer, Rene
Strohmaier, Jana
Ruderfer, Douglas M.
Moran, Jennifer L.
Chambert, Kimberly D.
Sanders, Alan R.
Shi, Jianxin
Kendler, Kenneth
Riley, Brien
O'Neill, Tony
Walsh, Dermot
Malhotra, Dheeraj
Corvin, Aiden
Purcell, Shaun
Sklar, Pamela
Iwata, Nakao
Hultman, Christina M.
Sullivan, Patrick F.
Sebat, Jonathan
McCarthy, Shane
Gejman, Pablo V.
Levinson, Douglas F.
Owen, Michael J.
O'Donovan, Michael C.
Lencz, Todd
Kirov, George
CA Mol Genetics Schizophrenia
Wellcome Trust Case Control
TI Implication of a Rare Deletion at Distal 16p11.2 in Schizophrenia
SO JAMA PSYCHIATRY
LA English
DT Article
ID COPY-NUMBER VARIATION; HIDDEN-MARKOV MODEL; SNP GENOTYPING DATA;
DE-NOVO; DEVELOPMENTAL DELAY; DISEASE; GENE; POPULATION; MUTATIONS;
PHENOTYPE
AB Context: Large genomic copy number variations have been implicated as strong risk factors for schizophrenia. However, the rarity of these events has created challenges for the identification of further pathogenic loci, and extremely large samples are required to provide convincing replication.
Objective: To detect novel copy number variations that increase the susceptibility to schizophrenia by using 2 ethnically homogeneous discovery cohorts and replication in large samples.
Design: Genetic association study of microarray data.
Setting: Samples of DNA were collected at 9 sites from different countries.
Participants: Two discovery cohorts consisted of 790 cases with schizophrenia and schizoaffective disorder and 1347 controls of Ashkenazi Jewish descent and 662 parent-offspring trios from Bulgaria, of which the offspring had schizophrenia or schizoaffective disorder. Replication data sets consisted of 12 398 cases and 17 945 controls.
Main Outcome Measures: Statistically increased rate of specific copy number variations in cases vs controls.
Results: One novel locus was implicated: a deletion at distal 16p11.2, which does not overlap the proximal 16p11.2 locus previously reported in schizophrenia and autism. Deletions at this locus were found in 13 of 13 850 cases (0.094%) and 3 of 19 954 controls (0.015%) (odds ratio, 6.25 [95% CI, 1.78-21.93]; P=.001, Fisher exact test).
Conclusions: Deletions at distal 16p11.2 have been previously implicated in developmental delay and obesity. The region contains 9 genes, several of which are implicated in neurological diseases, regulation of body weight, and glucose homeostasis. A telomeric extension of the deletion, observed in about half the cases but no controls, potentially implicates an additional 8 genes. Our findings add a new locus to the list of copy number variations that increase the risk for development of schizophrenia. JAMA Psychiatry. 2013; 70(3): 253-260. Published online January 16, 2013. doi:10.1001/2013.jamapsychiatry.71
C1 [Guha, Saurav; Kane, John M.; Malhotra, Anil K.; Lencz, Todd] Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY 11004 USA.
[Rees, Elliott; Ivanov, Dobril; Owen, Michael J.; O'Donovan, Michael C.; Kirov, George] Cardiff Univ, Med Res Council, Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales.
[Rees, Elliott; Ivanov, Dobril; Owen, Michael J.; O'Donovan, Michael C.; Kirov, George] Cardiff Univ, Neurosci & Mental Hlth Res Inst, Cardiff CF10 3AX, S Glam, Wales.
[Darvasi, Ariel] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel.
[Ikeda, Masashi; Iwata, Nakao] Fujita Hlth Univ, Sch Med, Toyoake, Aichi 47011, Japan.
[Bergen, Sarah E.; Purcell, Shaun] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Bergen, Sarah E.; Purcell, Shaun] Harvard Univ, Sch Med, Boston, MA USA.
[Bergen, Sarah E.; Purcell, Shaun] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Bergen, Sarah E.; Moran, Jennifer L.; Chambert, Kimberly D.; Purcell, Shaun] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[Magnusson, Patrik K.; Hultman, Christina M.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Cormican, Paul; Morris, Derek; Gill, Michael; Corvin, Aiden] Trinity Coll Dublin, Dept Psychiat, Dublin, Ireland.
[Walsh, Dermot] Hlth Res Board, Dublin, Ireland.
[Cichon, Sven; Noethen, Markus M.; Degenhardt, Franziska; Priebe, Lutz] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Cichon, Sven; Degenhardt, Franziska; Priebe, Lutz] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany.
[Noethen, Markus M.] Ctr Neurodegenerat Dis, Bonn, Germany.
[Cichon, Sven] Res Ctr Juelich, Inst Neurosci & Med, Julich, Germany.
[Rosenfeld, Jeffrey A.] Univ Med & Dent New Jersey, IST High Performance & Res Comp, Newark, NJ 07103 USA.
[Lee, Annette; Gregersen, Peter K.] Feinstein Inst Med Res, Robert S Boas Ctr Human Genet & Genom, Manhasset, NY USA.
[Kane, John M.; Malhotra, Anil K.; Lencz, Todd] Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA.
[Kane, John M.; Malhotra, Anil K.; Lencz, Todd] Hofstra Univ, Sch Med, Dept Psychiat, Long Isl City, NY USA.
[Rietschel, Marcella; Breuer, Rene; Strohmaier, Jana] Heidelberg Univ, Cent Inst Mental Hlth, Med Fac Mannheim, Mannheim, Germany.
[Ruderfer, Douglas M.; Purcell, Shaun; Sklar, Pamela] Mt Sinai Sch Med, Dept Psychiat, Div Psychiat Genom, New York, NY USA.
[Sanders, Alan R.; Gejman, Pablo V.] NorthShore Univ, HealthSyst Res Inst, Dept Psychiat & Behav Sci, Evanston, IL USA.
[Sanders, Alan R.; Gejman, Pablo V.] Univ Chicago, Dept Psychiat & Behav Sci, Chicago, IL 60637 USA.
[Shi, Jianxin] NCI, Bethesda, MD 20892 USA.
[Kendler, Kenneth] Virginia Commonwealth Univ, Sch Med, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23284 USA.
[Riley, Brien] Virginia Commonwealth Univ, Sch Med, Dept Psychiat, Richmond, VA 23284 USA.
[O'Neill, Tony] Queens Univ, Dept Psychiat, Belfast, Ireland.
[Malhotra, Dheeraj; Sebat, Jonathan] Univ Calif San Diego, Beyster Ctr Genom Psychiat Dis, La Jolla, CA 92093 USA.
[Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Sullivan, Patrick F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[McCarthy, Shane] Woodbury Genome Ctr, Cold Spring Harbor Lab, Stanley Inst Cognit Genom, Cold Spring on Hudson, NY USA.
[Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
RP Lencz, T (reprint author), Zucker Hillside Hosp, Div Psychiat Res, 75-59 263rd st, Glen Oaks, NY 11004 USA.
EM tlencz@NSHS.edu; Kirov@cardiff.ac.uk
RI Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Ruderfer,
Douglas/M-5795-2016; Lencz, Todd/J-3418-2014; Magnusson,
Patrik/C-4458-2017;
OI Gill, Michael/0000-0003-0206-5337; Ivanov, Dobril/0000-0001-6271-6301;
Moran, Jennifer/0000-0002-5664-4716; Nothen, Markus/0000-0002-8770-2464;
Cichon, Sven/0000-0002-9475-086X; Corvin, Aiden/0000-0001-6717-4089;
O'Donovan, Michael/0000-0001-7073-2379; Guha,
Saurav/0000-0002-0620-5408; Morris, Derek/0000-0002-3413-570X; Cichon,
Sven/0000-0002-9475-086X; Ruderfer, Douglas/0000-0002-2365-386X; Lencz,
Todd/0000-0001-8586-338X; Bergen, Sarah/0000-0002-5888-0034; Sebat,
Jonathan/0000-0002-9087-526X
FU Medical Research Council [G0800509]; National Institute of Mental Health
(NIMH) [2 P50 MH066392-05A1]; EU-GEI from the European Union; Stanley
Medical Research Institute; Merck Genome Research Foundation; Herman
Foundation; North Shore-Long Island Jewish Health System Foundation;
National Institutes of Health [RC2 MH089964, R01 MH084098, P50 MH080173,
P30 MH090590]; NIMH [MH67257, H59588, MH59571, MH59565, MH59587,
MH60870, MH59566, MH59586, MH61675, MH60879, MH81800, MH46276, MH46289,
MH46318, MH79469, MH79470]; National Alliance for Research on
Schizophrenia and Depression; Genetic Association Information Network;
Paul Michael Donovan Charitable Foundation; Walter E. Nichols, MD, and
Eleanor Nichols endowments (Stanford University); National Center for
Research Resources [U54 RR020278]; German Federal Ministry of Education
and Research (BMBF) [01GS08144, 01GS08147]; Wellcome Trust
[085475/B/08/Z, 085475/Z/08/Z, 068545/Z/02]; UK Medical Research Council
[G0000934]; UK National Blood Service; Japan Ministry of Education,
Culture, Sports, Science and Technology; Ministry of Health, Labor and
Welfare; Core Research for Evolutional Science and Technology; Health
Sciences Foundation (Research on Health Sciences focusing on Drug
Innovation)
FX Work at Cardiff University was supported by grant G0800509 from the
Medical Research Council Programme and Centre Grants, grant 2 P50
MH066392-05A1 from the National Institute of Mental Health (NIMH), and
grant EU-GEI from the European Union. Genotyping was funded by multiple
grants to the Stanley Center for Psychiatric Research at the Broad
Institute from the Stanley Medical Research Institute, the Merck Genome
Research Foundation, and the Herman Foundation. The Zucker Hillside
Hospital work was supported by the North Shore-Long Island Jewish Health
System Foundation and grants RC2 MH089964 (Dr Lencz), R01 MH084098 (Dr
Lencz), P50 MH080173 (Dr A. K. Malhotra), and P30 MH090590 (Dr Kane)
from the National Institutes of Health. Molecular Genetics of
Schizophrenia Consortium data collection was supported by R01 grants
MH67257, H59588, MH59571, MH59565, MH59587, MH60870, MH59566, MH59586,
MH61675, MH60879, and MH81800 and U01 grants MH46276, MH46289, MH46318,
MH79469, and MH79470 from the NIMH. We acknowledge support through Young
Investigator Awards (Dr Sanders and Jubao Duan, PhD) from the National
Alliance for Research on Schizophrenia and Depression and from the
Genetic Association Information Network, the Paul Michael Donovan
Charitable Foundation, and the Walter E. Nichols, MD, and Eleanor
Nichols endowments (Stanford University). Genotyping performed by the
Center for Genotyping and Analysis at the Broad Institute of Harvard and
Massachusetts Institute of Technology was supported by grant U54
RR020278 from the National Center for Research Resources. The German
study was supported by grants 01GS08144 and 01GS08147 from the German
Federal Ministry of Education and Research (BMBF), within the context of
the Integrated Genome Research Network MooDS (Systematic Investigation
of the Molecular Causes of Major Mood Disorders and Schizophrenia).
Control data were provided by the community-based studies of PopGen
(Population-based Recruitment of Patients and Controls for the Analysis
of Complex Genotype-Phenotype Relationships), Cooperative Health
Research in the Region Augsburg, the Heinz Nixdorf Recall study, and
MooDS. Genotyping of Wellcome Trust Case Control Consortium 2 samples
was funded by grants 085475/B/08/Z and 085475/Z/08/Z from the Wellcome
Trust. The British 1958 Birth Cohort DNA collection was funded by grant
G0000934 from the UK Medical Research Council and grant 068545/Z/02 from
the Wellcome Trust, and the UK National Blood Service controls by the
Wellcome Trust. The Japanese cohort was supported in part by research
grants from the Japan Ministry of Education, Culture, Sports, Science
and Technology; the Ministry of Health, Labor and Welfare; the Core
Research for Evolutional Science and Technology; and the Health Sciences
Foundation (Research on Health Sciences focusing on Drug Innovation).
NR 28
TC 23
Z9 23
U1 2
U2 17
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-622X
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD MAR
PY 2013
VL 70
IS 3
BP 253
EP 260
DI 10.1001/2013.jamapsychiatry.71
PG 8
WC Psychiatry
SC Psychiatry
GA 114GY
UT WOS:000316730300002
PM 23325106
ER
PT J
AU Furey, ML
Drevets, WC
Hoffman, EM
Frankel, E
Speer, AM
Zarate, CA
AF Furey, Maura L.
Drevets, Wayne C.
Hoffman, Elana M.
Frankel, Erica
Speer, Andrew M.
Zarate, Carlos A., Jr.
TI Potential of Pretreatment Neural Activity in the Visual Cortex During
Emotional Processing to Predict Treatment Response to Scopolamine in
Major Depressive Disorder
SO JAMA PSYCHIATRY
LA English
DT Article
ID RAPID ANTIDEPRESSANT RESPONSE; CEREBRAL-BLOOD-FLOW; WORKING-MEMORY;
CHOLINERGIC ENHANCEMENT; FUNCTIONAL CONNECTIVITY; SELECTIVE ATTENTION;
FACIAL EXPRESSIONS; PREFRONTAL CORTEX; MOOD-STATE; MODULATION
AB Context: The need for improved treatment options for patients with major depressive disorder (MDD) is critical. Faster-acting antidepressants and biomarkers that predict clinical response will facilitate treatment. Scopolamine produces rapid antidepressant effects and thus offers the opportunity to characterize potential biomarkers of treatment response within short periods.
Objective: To determine if baseline brain activity when processing emotional information can predict treatment response to scopolamine in MDD.
Design: A double-blind, placebo-controlled, crossover study together with repeated functional magnetic resonance imaging, acquired as participants performed face-identity and face-emotion working memory tasks.
Setting: National Institute of Mental Health Division of Intramural Research Programs.
Participants: Fifteen currently depressed outpatients meeting DSM-IV criteria for recurrent MDD and 21 healthy participants, between 18 and 55 years of age.
Main Outcome Measure: The magnitude of treatment response to scopolamine (percentage of change in the Montgomery-Asberg Depression Rating Scale score between study end and baseline) was correlated with blood oxygenlevel-dependent(BOLD) signal associated with each working memory component (encode, maintenance, and test) for both identity and emotion tasks. Treatment response also was correlated with change in BOLD response (scopolamine vs baseline). Baseline activity was compared between healthy and MDD groups.
Results: Baseline BOLD response in the bilateral middle occipital cortex, selectively during the stimulus-processing components of the emotion working memory task (no correlation during the identity task), correlated with treatment response magnitude. Change in BOLD response following scopolamine administration in overlapping areas in the middle occipital cortex while performing the same task conditions also correlated with clinical response. Healthy controls showed higher activity in the same visual regions than patients with MDD during baseline.
Conclusion: These results implicate cholinergic and visual processing dysfunction in the pathophysiology of MDD and suggest that neural response in the visual cortex, selectively to emotional stimuli, may provide a useful biomarker for identifying patients who will respond favorably to scopolamine. Trial Registration: clinicaltrials.gov Identifier: NCT00055575 JAMA Psychiatry. 2013; 70(3): 280-290. Published online January 30, 2013. doi:10.1001/2013.jamapsychiatry.60
C1 [Furey, Maura L.; Frankel, Erica; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
[Speer, Andrew M.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Drevets, Wayne C.] Univ Oklahoma, Laureate Inst Brain Res, Coll Med, Tulsa, OK USA.
[Drevets, Wayne C.] Univ Oklahoma, Dept Psychiat, Coll Med, Tulsa, OK USA.
[Hoffman, Elana M.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA.
RP Furey, ML (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, NIH, 15K North Dr,Bldg 15K,Room 115B, Bethesda, MD 20892 USA.
EM mfurey@mail.nih.gov
RI Furey, Maura/H-5273-2013
FU National Institutes of Health National Institute of Mental Health
Division of Intramural Research Programs
FX This research was supported by the National Institutes of Health
National Institute of Mental Health Division of Intramural Research
Programs.
NR 58
TC 29
Z9 30
U1 4
U2 16
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-622X
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD MAR
PY 2013
VL 70
IS 3
BP 280
EP 290
DI 10.1001/2013.jamapsychiatry.60
PG 11
WC Psychiatry
SC Psychiatry
GA 114GY
UT WOS:000316730300005
PM 23364679
ER
PT J
AU Gabay, O
Gabay, C
AF Gabay, Odile
Gabay, Cem
TI Hand osteoarthritis: New insights
SO JOINT BONE SPINE
LA English
DT Review
DE Hand OA; Biology; Genetic
ID KNEE OSTEOARTHRITIS; EROSIVE OSTEOARTHRITIS; GENERAL-POPULATION;
OBESE-PATIENTS; DOUBLE-BLIND; WEIGHT-LOSS; ASSOCIATION; HIP; LEPTIN;
TRIAL
AB Hand osteoarthritis (OA) is one of the most common localization of OA affecting predominantly women. The etiology seems to be multifactorial and the disease heterogeneous, comprising several clinical and radiological subsets. Hand OA includes thumb base (trapeziometarcarpal joint), metacarpophalangeal joints, distal and proximal interphalangeal joints OA. We reviewed below the prevalence, diagnosis, imaging, epidemiology, risk factors, but mostly the last discoveries in the biology and pathophysiology with particular attention to the potential role of adipokines and genetic factors. Finally, we also reviewed the different treatments currently available as well as potential future therapies. (C) 2012 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
C1 [Gabay, Odile] NIAMSD, Cartilage Biol & Orthoped Branch, NIH, Bethesda, MD 20892 USA.
[Gabay, Cem] Univ Hosp Geneva, Div Rheumatol, CH-1211 Geneva 14, Switzerland.
RP Gabay, C (reprint author), Univ Hosp Geneva, Div Rheumatol, 26 Ave Beau Sejour, CH-1211 Geneva 14, Switzerland.
EM Cem.Gabay@hcuge.ch
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institute of Health; Swiss National Science Foundation
[310030-135195]; Rheumasearch Foundation; Institute of arthritis
Research
FX This research was supported in part by the Intramural Research Program
of the National Institute of Arthritis and Musculoskeletal and Skin
Diseases of the National Institute of Health (OG). CG is supported by a
Swiss National Science Foundation grant(310030-135195), the Rheumasearch
Foundation, and the Institute of arthritis Research.
NR 59
TC 3
Z9 3
U1 2
U2 11
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 1297-319X
J9 JOINT BONE SPINE
JI Joint Bone Spine
PD MAR
PY 2013
VL 80
IS 2
BP 130
EP 134
DI 10.1016/j.jbspin.2012.06.011
PG 5
WC Rheumatology
SC Rheumatology
GA 115ED
UT WOS:000316794500004
PM 22871418
ER
PT J
AU Kristensen, DM
Waller, AS
Yamada, T
Bork, P
Mushegian, AR
Koonin, EV
AF Kristensen, David M.
Waller, Alison S.
Yamada, Takuji
Bork, Peer
Mushegian, Arcady R.
Koonin, Eugene V.
TI Orthologous Gene Clusters and Taxon Signature Genes for Viruses of
Prokaryotes
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID STRAND RNA VIRUSES; EVOLUTIONARY GENOMICS; PROTEIN FAMILIES;
BACTERIOPHAGES; IDENTIFICATION; ARCHAEA; GENERATION; SIMILARITY;
DIVERSITY; ALGORITHM
AB Viruses are the most abundant biological entities on earth and encompass a vast amount of genetic diversity. The recent rapid increase in the number of sequenced viral genomes has created unprecedented opportunities for gaining new insight into the structure and evolution of the virosphere. Here, we present an update of the phage orthologous groups (POGs), a collection of 4,542 clusters of orthologous genes from bacteriophages that now also includes viruses infecting archaea and encompasses more than 1,000 distinct virus genomes. Analysis of this expanded data set shows that the number of POGs keeps growing without saturation and that a substantial majority of the POGs remain specific to viruses, lacking homologues in prokaryotic cells, outside known proviruses. Thus, the great majority of virus genes apparently remains to be discovered. A complementary observation is that numerous viral genomes remain poorly, if at all, covered by POGs. The genome coverage by POGs is expected to increase as more genomes are sequenced. Taxon-specific, single-copy signature genes that are not observed in prokaryotic genomes outside detected proviruses were identified for two-thirds of the 57 taxa (those with genomes available from at least 3 distinct viruses), with half of these present in all members of the respective taxon. These signatures can be used to specifically identify the presence and quantify the abundance of viruses from particular taxa in metagenomic samples and thus gain new insights into the ecology and evolution of viruses in relation to their hosts.
C1 [Kristensen, David M.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Waller, Alison S.; Bork, Peer] European Mol Biol Lab, D-69012 Heidelberg, Germany.
[Yamada, Takuji] Tokyo Inst Technol, Midori Ku, Yokohama, Kanagawa 227, Japan.
[Mushegian, Arcady R.] Stowers Inst Med Res, Kansas City, MO USA.
[Mushegian, Arcady R.] Univ Kansas, Med Ctr, Dept Microbiol, Kansas City, KS 66103 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM koonin@ncbi.nlm.nih.gov
RI Bork, Peer/F-1813-2013;
OI Bork, Peer/0000-0002-2627-833X; Mushegian, Arcady/0000-0002-6809-9225
FU U.S. Department of Health and Human Services; Stowers Institute for
Medical Research
FX D.M.K. and E.V.K. are supported by intramural funds of the U.S.
Department of Health and Human Services (to the National Library of
Medicine). A.R.M. was supported by the Stowers Institute for Medical
Research.
NR 47
TC 35
Z9 35
U1 1
U2 30
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 MAR
PY 2013
VL 195
IS 5
BP 941
EP 950
DI 10.1128/JB.01801-12
PG 10
WC Microbiology
SC Microbiology
GA 117NY
UT WOS:000316961400004
PM 23222723
ER
EF