FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Lu, TJ
Lu, RB
Hong, JS
Yang, YK
Yu, L
AF Lu, Tsun-Jung
Lu, Ru-Band
Hong, Jau-Shyong
Yang, Yen Kuang
Yu, Lung
TI Impairment of an Electroconvulsive Stimulus on Reconsolidation of
Memories Established by Conditioning
SO CHINESE JOURNAL OF PHYSIOLOGY
LA English
DT Article
DE memory; reconsolidation; recall; ECT; cocaine; appetitive; passive
avoidance
ID BISPECTRAL INDEX; MOLECULAR-MECHANISMS; RETROGRADE-AMNESIA; THERAPY;
CONSOLIDATION; ANTEROGRADE; AVOIDANCE; RETRIEVAL
AB The deduced memory consolidation and reconsolidation phases are sensitive to similar amnesic and memory-enhancing treatment. Electroconvulsive stimulus has been well known to impair memory consolidation. Therefore, we hypothesized that electroconvulsive stimulus might disrupt reconsolidation for conditioning-established memories. Delivery of a 200-msec electroconvulsive stimulus (500 V, 25 mA) between mouse pinnas immediately after recall of the cocaine-induced conditioned place preference (CPP) impaired the reconsolidation and subsequent expression of this memory. In contrast, the electroconvulsive stimulus (500 V, 25 mA, lasting for 200 ms) did not affect subsequent cocaine-induced CPP performance when the recall procedure was omitted. Systemic pentobarbital injection immediately after the CPP test did not affect subsequent cocaine-induced CPP. Interestingly, several regimens of electroconvulsive stimulus given immediately after the recall of cocaine-induced CPP did not affect subsequent CPP performance when mice were anesthetized by pentobarbital throughout the ECS regimens. Finally, delivery of the ECS (500 V, 25 mA, lasting for 200 ms) immediately after the reactivation of passive avoidance (PA) and food-induced CPP impaired subsequent performance of these memories in the retest. Taken together, we conclude that a short-lasting electroconvulsive stimulus can deteriorate the reconsolidation of various forms of memory established by conditioning.
C1 [Lu, Tsun-Jung; Yu, Lung] Natl Cheng Kung Univ, Coll Med, Inst Behav Med, Tainan 70101, Taiwan.
[Lu, Ru-Band; Yang, Yen Kuang] Natl Cheng Kung Univ, Coll Med, Dept Psychiat, Tainan 70101, Taiwan.
[Hong, Jau-Shyong] NIEHS, Labs Toxicol & Pharmacol, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Yu, L (reprint author), Natl Cheng Kung Univ, Coll Med, Inst Behav Med, Behav Neuropharmacol Lab, 1 Univ Rd, Tainan 70101, Taiwan.
EM lungyu@mail.ncku.edu.tw
FU ROC National Science Council [97-2321-B-006-010-, 97-2410-H-006-074-MY3]
FX This research is supported, in part, by ROC National Science Council
grants 97-2321-B-006-010- and 97-2410-H-006-074-MY3 to L.Y.
NR 26
TC 1
Z9 1
U1 0
U2 8
PU CHINESE PHYSIOLOGICAL SOC
PI TAIPEI
PA NATL YANG-MING UNIV, TAIPEI, TAIWAN
SN 0304-4920
J9 CHINESE J PHYSIOL
JI Chin. J. Physiol.
PD FEB 28
PY 2013
VL 56
IS 1
BP 44
EP 51
DI 10.4077/CJP.2013.BAA048
PG 8
WC Physiology
SC Physiology
GA 097MK
UT WOS:000315478000006
PM 23347015
ER
PT J
AU Oka, Y
Butnaru, M
von Buchholtz, L
Ryba, NJP
Zuker, CS
AF Oka, Yuki
Butnaru, Matthew
von Buchholtz, Lars
Ryba, Nicholas J. P.
Zuker, Charles S.
TI High salt recruits aversive taste pathways
SO NATURE
LA English
DT Article
ID CARBONIC-ANHYDRASE-IV; BITTER TASTE; IN-VIVO; AMILORIDE; RECEPTOR;
CELLS; MICE; NACL; DISCRIMINATION; TRANSDUCTION
AB In the tongue, distinct classes of taste receptor cells detect the five basic tastes; sweet, sour, bitter, sodium salt and umami(1,2). Among these qualities, bitter and sour stimuli are innately aversive, whereas sweet and umami are appetitive and generally attractive to animals. By contrast, salty taste is unique in that increasing salt concentration fundamentally transforms an innately appetitive stimulus into a powerfully aversive one(3-7). This appetitive-aversive balance helps to maintain appropriate salt consumption(3,4,6,8), and represents an important part of fluid and electrolyte homeostasis. We have shown previously that the appetitive responses to NaCl are mediated by taste receptor cells expressing the epithelial sodium channel, ENaCs8, but the cellular substrate for salt aversion was unknown. Here we examine the cellular and molecular basis for the rejection of high concentrations of salts. We show that high salt recruits the two primary aversive taste pathways by activating the sour- and bitter-taste-sensing cells. We also demonstrate that genetic silencing of these pathways abolishes behavioural aversion to concentrated salt, without impairing salt attraction. Notably, mice devoid of salt-aversion pathways show unimpeded, continuous attraction even to very high concentrations of NaCl. We propose that the 'co-opting' of sour and bitter neural pathways evolved as a means to ensure that high levels of salt reliably trigger robust behavioural rejection, thus preventing its potentially detrimental effects on health.
C1 [Oka, Yuki; Butnaru, Matthew; Zuker, Charles S.] Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA.
[Oka, Yuki; Butnaru, Matthew; Zuker, Charles S.] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
[Oka, Yuki; Butnaru, Matthew; Zuker, Charles S.] Columbia Univ, Dept Neurosci, Columbia Coll Phys & Surg, New York, NY 10032 USA.
[von Buchholtz, Lars; Ryba, Nicholas J. P.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
RP Zuker, CS (reprint author), Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA.
EM nick.ryba@nih.gov; cz2195@columbia.edu
FU Japan Society for Promotion of Science; National Institutes of Health
and National Institute of Dental and Craniofacial Research
FX We thank E. Vitalis and N. Propp for the generation and maintenance of
mouse lines, and K. Mueller for the construction of T2R-Sapphire lines.
We also thank J. Chandrashekar, W. Sly and A. Waheed for advice and
discussions, and K. Scott and members of our laboratories for comments.
Y.O. was supported by the Japan Society for Promotion of Science. This
research was supported in part by the intramural research program of the
National Institutes of Health and National Institute of Dental and
Craniofacial Research (to N.J.P.R.). C.S.Z. is an investigator of the
Howard Hughes Medical Institute.
NR 30
TC 63
Z9 64
U1 4
U2 108
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD FEB 28
PY 2013
VL 494
IS 7438
BP 472
EP 475
DI 10.1038/nature11905
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099YI
UT WOS:000315661500037
PM 23407495
ER
PT J
AU Kovalchik, SA
Varadhan, R
Fetterman, B
Poitras, NE
Wacholder, S
Katki, HA
AF Kovalchik, Stephanie A.
Varadhan, Ravi
Fetterman, Barbara
Poitras, Nancy E.
Wacholder, Sholom
Katki, Hormuzd A.
TI A general binomial regression model to estimate standardized risk
differences from binary response data
SO STATISTICS IN MEDICINE
LA English
DT Article
DE absolute risk; binomial regression; constrained maximization; logistic
regression; risk difference
ID EPIDEMIOLOGIC ANALYSES; ODDS RATIO; CYTOLOGY
AB Estimates of absolute risks and risk differences are necessary for evaluating the clinical and population impact of biomedical research findings. We have developed a linear-expit regression model (LEXPIT) to incorporate linear and nonlinear risk effects to estimate absolute risk from studies of a binary outcome. The LEXPIT is a generalization of both the binomial linear and logistic regression models. The coefficients of the LEXPIT linear terms estimate adjusted risk differences, whereas the exponentiated nonlinear terms estimate residual odds ratios. The LEXPIT could be particularly useful for epidemiological studies of risk association, where adjustment for multiple confounding variables is common. We present a constrained maximum likelihood estimation algorithm that ensures the feasibility of risk estimates of the LEXPIT model and describe procedures for defining the feasible region of the parameter space, judging convergence, and evaluating boundary cases. Simulations demonstrate that the methodology is computationally robust and yields feasible, consistent estimators. We applied the LEXPIT model to estimate the absolute 5-year risk of cervical precancer or cancer associated with different Pap and human papillomavirus test results in 167,171 women undergoing screening at Kaiser Permanente Northern California. The LEXPIT model found an increased risk due to abnormal Pap test in human papillomavirus-negative that was not detected with logistic regression. Our R package blm provides free and easy-to-use software for fitting the LEXPIT model. Published 2012. This article is a US Government work and is in the public domain in the USA.
C1 [Kovalchik, Stephanie A.; Wacholder, Sholom; Katki, Hormuzd A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Varadhan, Ravi] Johns Hopkins Univ, Sch Med, Ctr Aging Hlth, Baltimore, MD USA.
[Fetterman, Barbara; Poitras, Nancy E.] Kaiser Permanente No Calif, Berkeley, CA USA.
RP Kovalchik, SA (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
EM kovalchiksa@nih.gov
RI Katki, Hormuzd/B-4003-2015
FU NIH/NCI
FX This research was supported by the intramural research program of the
NIH/NCI. We thank Dr. Tom Lorey and Dr. Gene Pawlick (Regional
Laboratory of the Northern California Kaiser Permanente Medical Care
Program) for creating and supporting the data warehouse, and Kaiser
Permanente Northern California for allowing use of the data.
NR 32
TC 12
Z9 12
U1 1
U2 18
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD FEB 28
PY 2013
VL 32
IS 5
BP 808
EP 821
DI 10.1002/sim.5553
PG 14
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 089PW
UT WOS:000314923500006
PM 22865328
ER
PT J
AU Proschan, M
Ford, CE
Cutler, JA
Graumlich, JF
Pavlik, V
Cushman, WC
Davis, BR
Alderman, MH
Gordon, D
Furberg, CD
Franklin, SS
Blumenthal, SS
Castaldo, RS
Preston, RA
AF Proschan, Michael
Ford, Charles E.
Cutler, Jeffrey A.
Graumlich, James F.
Pavlik, Valory
Cushman, William C.
Davis, Barry R.
Alderman, Michael H.
Gordon, David
Furberg, Curt D.
Franklin, Stanley S.
Blumenthal, Samuel S.
Castaldo, Richard S.
Preston, Richard A.
CA ALLHAT Collaborative Res Grp
TI How much effect of different antihypertensive medications on
cardiovascular outcomes is attributable to their effects on blood
pressure?
SO STATISTICS IN MEDICINE
LA English
DT Article
DE blood pressure; measurement error; meta-analysis; regression
calibration; regression dilution bias; time-varying covariate analysis
ID LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT; CORONARY HEART-DISEASE;
HYPERTENSIVE PATIENTS; SURROGATE MARKER; CLINICAL-TRIALS; MAJOR
OUTCOMES; STROKE; PROPORTION; ENDPOINTS
AB The debate over whether certain antihypertensive medications have benefits beyond what would be expected from their blood pressure lowering spurred the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, which randomized 42,418 participants to chlorthalidone (15,255), amlodipine (9048), lisinopril (9054), or doxazosin (9061). We compared chlorthalidone, the active control, with each of the other three agents with respect to the primary outcome, fatal coronary heart disease or nonfatal myocardial infarction, and several other clinical endpoints. The arms were similar with respect to the primary endpoint, although some differences were found for other endpoints, most notably heart failure. Although the desire was to achieve similar blood pressure reductions in the four arms, we found some systolic blood pressure and diastolic blood pressure differences. A natural question is to what degree can observed treatment group differences in cardiovascular outcomes be attributed to these blood pressure differences. The purpose of this paper was to delineate the problems inherent in attempting to answer this question, and to present analyses intended to overcome these problems. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Proschan, Michael] NIAID, Bethesda, MD 20892 USA.
[Ford, Charles E.; Davis, Barry R.] Univ Texas Sch Publ Hlth, Houston, TX USA.
[Cutler, Jeffrey A.; Gordon, David] NHLBI, Bethesda, MD 20892 USA.
[Graumlich, James F.] Univ Illinois, Coll Med Peoria, Peoria, IL USA.
[Pavlik, Valory] Baylor Coll Med, Houston, TX 77030 USA.
[Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA.
[Alderman, Michael H.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Furberg, Curt D.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Franklin, Stanley S.] Univ Calif Irvine, Los Angeles, CA USA.
[Blumenthal, Samuel S.] Vet Affairs Med Ctr Milwaukee, Milwaukee, WI USA.
[Preston, Richard A.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Preston, Richard A.] Vet Affairs Med Ctr, Miami, FL 33125 USA.
RP Proschan, M (reprint author), NIAID, Biostat Res Branch, 6700A Rockledge Dr,Room 5140, Bethesda, MD 20892 USA.
EM ProschaM@mail.nih.gov
FU National Heart, Lung, and Blood Institute (NHLBI) [NO1-HC-35130]; Pfizer
Inc.; Abbott Laboratories; Bristol-Myers Squibb; Merck; Pfizer; Roche;
Wyeth; GlaxoSmithKline; King; Novartis; Bayer Corporation; Forest
Laboratories; Schering Plough; Shionogi; Takeda
FX The ALLHAT study was supported by contract NO1-HC-35130 with the
National Heart, Lung, and Blood Institute (NHLBI). The ALLHAT
investigators received contributions of study medications supplied by
Pfizer (amlodipine besylate and doxazosin mesylate), AstraZeneca
(atenolol and lisinopril), and Bristol-Myers Squibb (pravastatin), and
financial support provided by Pfizer Inc.; Michael H. Alderman has
received research support from Sankyo. Samuel S. Blumenthal has held a
financial interest in Abbott Laboratories, Bristol-Myers Squibb, Merck,
Pfizer, Roche, and Wyeth and has received honoraria from Boehringer
Ingelheim. William C. Cushman has consulted for Calpis, Daiichi Sankyo,
Gilead Colorado, Novartis, Noven, Pharmacopeia, Sanofi Aventis, Sciele,
Takeda, Theravance; has received honoraria from Bristol-Myer Squibb,
Forest Pharmaceuticals, King; and has received research support from
GlaxoSmithKline, King, Novartis, and Merck. Barry R. Davis has consulted
for Amgen, Forest Pharmaceuticals, and Takeda. Richard A. Preston has
consulted for Gilead Colorado and has received research support from
Abbott Laboratories, Bayer Corporation, Forest Laboratories, Merck,
Novartis, Schering Plough, Shionogi, and Takeda. Richard S. Castaldo,
Jeffrey A. Cutler, Charles E. Ford, Stanley S. Franklin, Curt D.
Furberg, David Gordon, James F. Graumlich, Valory Pavlik, and Michael
Proschan have no financial interests to report.
NR 21
TC 2
Z9 2
U1 0
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD FEB 28
PY 2013
VL 32
IS 5
BP 884
EP 897
DI 10.1002/sim.5580
PG 14
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 089PW
UT WOS:000314923500011
PM 22961832
ER
PT J
AU Pendse, J
Ramachandran, PV
Na, JB
Narisu, N
Fink, JL
Cagan, RL
Collins, FS
Baranski, TJ
AF Pendse, Jay
Ramachandran, Prasanna V.
Na, Jianbo
Narisu, Narisu
Fink, Jill L.
Cagan, Ross L.
Collins, Francis S.
Baranski, Thomas J.
TI A Drosophila functional evaluation of candidates from human genome-wide
association studies of type 2 diabetes and related metabolic traits
identifies tissue-specific roles for dHHEX
SO BMC GENOMICS
LA English
DT Article
DE Genome-wide association study; Drosophila melanogaster; Diabetes
mellitus; type 2; Hyperglycemia; Dyslipidemias; Phylogeny; Reverse
genetics; High-throughput screening assays; HHEX protein; human
ID INSULIN-RECEPTOR; RISK LOCI; CELLS; GROWTH; FLIES; HEX; TRIGLYCERIDES;
MUTATION; ENHANCER; HINDGUT
AB Background: Genome-wide association studies (GWAS) identify regions of the genome that are associated with particular traits, but do not typically identify specific causative genetic elements. For example, while a large number of single nucleotide polymorphisms associated with type 2 diabetes (T2D) and related traits have been identified by human GWAS, only a few genes have functional evidence to support or to rule out a role in cellular metabolism or dietary interactions. Here, we use a recently developed Drosophila model in which high-sucrose feeding induces phenotypes similar to T2D to assess orthologs of human GWAS-identified candidate genes for risk of T2D and related traits.
Results: Disrupting orthologs of certain T2D candidate genes (HHEX, THADA, PPARG, KCNJ11) led to sucrose-dependent toxicity. Tissue-specific knockdown of the HHEX ortholog dHHEX (CG7056) directed metabolic defects and enhanced lethality; for example, fat-body-specific loss of dHHEX led to increased hemolymph glucose and reduced insulin sensitivity.
Conclusion: Candidate genes identified in human genetic studies of metabolic traits can be prioritized and functionally characterized using a simple Drosophila approach. To our knowledge, this is the first large-scale effort to study the functional interaction between GWAS-identified candidate genes and an environmental risk factor such as diet in a model organism system.
C1 [Pendse, Jay; Na, Jianbo; Cagan, Ross L.] Mt Sinai Sch Med, Dept Dev & Regenerat Biol, New York, NY USA.
[Ramachandran, Prasanna V.; Fink, Jill L.; Baranski, Thomas J.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Narisu, Narisu; Collins, Francis S.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Baranski, TJ (reprint author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
EM baranski@wustl.edu
FU NIH [R21 DK069940, P60 DK20579, P20 RR020643]; NephCure Foundation;
American Diabetes Association; NIGMS, NIH [T32 GM-62754]; NHGRI, NIH
FX We thank Vivek A. Rudrapatna, Ruth I. Johnson, Susumu Hirabayashi, Erdem
Bangi, Tirtha Kamal Das, Laura Palanker Musselman, Dac Anh Nguyen, Lori
Bonnycastle, Michael Stitzel, Michael Erdos, and Laura Scott for advice
and helpful discussions, and countless members of the free and open
source software community for valuable guidance and code samples. This
research was supported by NIH grants R21 DK069940 (RLC), P60 DK20579
(Washington University DRTC, TJB), and P20 RR020643 (TJB), as well as by
grants from the NephCure Foundation (JN and RLC) and from the American
Diabetes Association (JN and RLC). JP was supported in part by NIGMS
Training Grant T32 GM-62754, NIH. NN and FSC were supported by the
intramural program of NHGRI, NIH.
NR 55
TC 9
Z9 9
U1 0
U2 9
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 FEB 27
PY 2013
VL 14
AR 136
DI 10.1186/1471-2164-14-136
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 113QB
UT WOS:000316681500001
PM 23445342
ER
PT J
AU Chen, L
Stuart, L
Ohsumi, TK
Burgess, S
Varshney, GK
Dastur, A
Borowsky, M
Benes, C
Lacy-Hulbert, A
Schmidt, EV
AF Chen, Li
Stuart, Lynda
Ohsumi, Toshiro K.
Burgess, Shawn
Varshney, Gaurav K.
Dastur, Anahita
Borowsky, Mark
Benes, Cyril
Lacy-Hulbert, Adam
Schmidt, Emmett V.
TI Transposon activation mutagenesis as a screening tool for identifying
resistance to cancer therapeutics
SO BMC CANCER
LA English
DT Article
DE Transposon mutagenesis; Chemotherapy; Resistance; Gene activation
ID PDZ DOMAIN PROTEINS; INSERTIONAL MUTAGENESIS; STEM-CELLS; SIGNALING
COMPLEXES; DRUG-SENSITIVITY; SLEEPING-BEAUTY; ION CHANNELS; GENOME;
PIGGYBAC; EXPRESSION
AB Background: The development of resistance to chemotherapies represents a significant barrier to successful cancer treatment. Resistance mechanisms are complex, can involve diverse and often unexpected cellular processes, and can vary with both the underlying genetic lesion and the origin or type of tumor. For these reasons developing experimental strategies that could be used to understand, identify and predict mechanisms of resistance in different malignant cells would be a major advance.
Methods: Here we describe a gain-of-function forward genetic approach for identifying mechanisms of resistance. This approach uses a modified piggyBac transposon to generate libraries of mutagenized cells, each containing transposon insertions that randomly activate nearby gene expression. Genes of interest are identified using next-gen high-throughput sequencing and barcode multiplexing is used to reduce experimental cost.
Results: Using this approach we successfully identify genes involved in paclitaxel resistance in a variety of cancer cell lines, including the multidrug transporter ABCB1, a previously identified major paclitaxel resistance gene. Analysis of co-occurring transposons integration sites in single cell clone allows for the identification of genes that might act cooperatively to produce drug resistance a level of information not accessible using RNAi or ORF expression screening approaches.
Conclusion: We have developed a powerful pipeline to systematically discover drug resistance in mammalian cells in vitro. This cost-effective approach can be readily applied to different cell lines, to identify canonical or context specific resistance mechanisms. Its ability to probe complex genetic context and non-coding genomic elements as well as cooperative resistance events makes it a good complement to RNAi or ORF expression based screens.
C1 [Chen, Li; Dastur, Anahita; Benes, Cyril] Massachusetts Gen Hosp, Ctr Canc Res, Ctr Mol Therapeut, Charlestown, MA 02129 USA.
[Chen, Li; Dastur, Anahita; Benes, Cyril] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Chen, Li; Stuart, Lynda; Lacy-Hulbert, Adam; Schmidt, Emmett V.] Massachusetts Gen Hosp, Program Dev Immunol, Boston, MA 02115 USA.
[Chen, Li; Stuart, Lynda; Lacy-Hulbert, Adam; Schmidt, Emmett V.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Ohsumi, Toshiro K.; Borowsky, Mark] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02115 USA.
[Ohsumi, Toshiro K.; Borowsky, Mark] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Burgess, Shawn; Varshney, Gaurav K.] NHGRI, Dev Genom Sect, Genome Technol Branch, Bethesda, MD 20892 USA.
RP Chen, L (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Ctr Mol Therapeut, CNY 149 Rm7308,13th St, Charlestown, MA 02129 USA.
EM lchen13@partners.org
RI Varshney, Gaurav/L-5261-2014;
OI Burgess, Shawn/0000-0003-1147-0596; Lacy-Hulbert,
Adam/0000-0003-2162-0156; Varshney, Gaurav K./0000-0002-0429-1904
FU National Institutes of Health [U01-AI070330]; Wellcome Trust [086357]
FX This work was supported by National Institutes of Health grant
(U01-AI070330). LC, AD, and CB received additional funding from the
Wellcome Trust (086357).
NR 50
TC 10
Z9 10
U1 0
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD FEB 27
PY 2013
VL 13
AR 93
DI 10.1186/1471-2407-13-93
PG 15
WC Oncology
SC Oncology
GA 103NA
UT WOS:000315922700001
PM 23442791
ER
PT J
AU Maltsev, AS
Chen, J
Levine, RL
Bax, A
AF Maltsev, Alexander S.
Chen, Jue
Levine, Rodney L.
Bax, Ad
TI Site-Specific Interaction between alpha-Synuclein and Membranes Probed
by NMR-Observed Methionine Oxidation Rates
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; A-BETA COMPONENT; PARKINSONS-DISEASE;
NEURODEGENERATIVE DISEASES; ALZHEIMERS-DISEASE; MASS-SPECTROMETRY;
PRECURSOR PROTEIN; BINDING; STRESS; AGGREGATION
AB alpha-Synuclein (alpha S) is an intrinsically disordered protein that is water-soluble but also can bind negatively charged lipid membranes while adopting an alpha-helical conformation. Membrane affinity is increased by post-translational N-terminal acetylation, a common modification in all eukaryotic cells. In the presence of lipid vesicles containing a small fraction of peroxidized lipids, the N-terminal Met residues in alpha S (Met1 and Met5) rapidly oxidize while reducing the toxic lipid hydroperoxide to a nonreactive lipid hydroxide, whereas C-terminal Met residues remain unaffected. Met oxidation can be probed conveniently and quantitatively by NMR spectroscopy. The results show that oxidation of Met1 reduces the rate of oxidation of Met5 and vice versa as a result of decreased membrane affinity of the partially oxidized protein. The effect of Met oxidation on the alpha S-membrane affinity extends over large distances, as in the V49M mutant, oxidation of Met1 and Met5 strongly impacts the oxidation rate of Met49 and vice versa. When not bound to membrane, oxidized Met1 and Met5 of alpha S are excellent substrates for methionine sulfoxide reductase (Msr), thereby providing an efficient vehicle for water-soluble Msr enzymes to protect the membrane against oxidative damage.
C1 [Maltsev, Alexander S.; Bax, Ad] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Jue; Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM bax@nih.gov
RI Levine, Rodney/D-9885-2011
FU NIDDK; NHLBI; Office of the Director, NIH
FX This work was supported by the Intramural Research Program of NIDDK and
NHLBI and the Intramural Antiviral Target Program of the Office of the
Director, NIH. We thank Nelson Cole for useful discussions and Barbara
S. Berlett for accelerating lipid peroxidation by gamma irradiation.
NR 36
TC 20
Z9 20
U1 2
U2 46
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD FEB 27
PY 2013
VL 135
IS 8
BP 2943
EP 2946
DI 10.1021/ja312415q
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 099KC
UT WOS:000315618900020
PM 23398174
ER
PT J
AU Reiner, JE
Robertson, JWF
Burden, DL
Burden, LK
Balijepalli, A
Kasianowicz, JJ
AF Reiner, Joseph E.
Robertson, Joseph W. F.
Burden, Daniel L.
Burden, Lisa K.
Balijepalli, Arvind
Kasianowicz, John J.
TI Temperature Sculpting in Yoctoliter Volumes
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID MOLECULE FLUORESCENCE SPECTROSCOPY; ALPHA-HEMOLYSIN CHANNELS; FLOW
CIRCULAR-DICHROISM; BILAYER-LIPID MEMBRANES; NANOMETER-SCALE PORE; GOLD
NANOPARTICLES; ION-CHANNEL; CONFORMATIONAL DYNAMICS;
POLYETHYLENE-GLYCOL; MASS-SPECTROMETRY
AB The ability to perturb large ensembles of molecules from equilibrium led to major advances in understanding reaction mechanisms in chemistry and biology. Here, we demonstrate the ability to control, measure, and make use of rapid temperature changes in fluid volumes that are commensurate with the size of single molecules. The method is based on attaching gold nanoparticles to a single nanometer-scale pore formed by a protein ion channel. Visible laser light incident on the nanoparticles causes a rapid and large increase of the adjacent solution temperature, which is estimated from the change in the nanopore ionic conductance. The temperature shift also affects the ability of individual molecules to enter into and interact with the nanopore. This technique could significantly improve sensor systems and force measurements based on single nanopores, thereby enabling a method for single molecule thermodynamics and kinetics.
C1 [Reiner, Joseph E.] Virginia Commonwealth Univ, Dept Phys, Richmond, VA 23284 USA.
[Robertson, Joseph W. F.; Balijepalli, Arvind; Kasianowicz, John J.] NIST, Semicond & Dimens Metrol Div, Phys Measurement Lab, Gaithersburg, MD 20899 USA.
[Burden, Daniel L.] Wheaton Coll, Dept Chem, Wheaton, IL 60187 USA.
[Burden, Lisa K.] Wheaton Coll, Dept Biol, Wheaton, IL 60187 USA.
[Balijepalli, Arvind] NHLBI, Lab Computat Biol, NIH, Rockville, MD 20892 USA.
RP Reiner, JE (reprint author), Virginia Commonwealth Univ, Dept Phys, Richmond, VA 23284 USA.
EM jereiner@vcu.edu; joseph.robertson@nist.gov; john.kasianowicz@nist.gov
OI Reiner, Joseph/0000-0002-1056-8703
FU NRC/NIST-NIH; NIST-ARRA; NIST Office of Law Enforcement Standards; NSF
FX This work was supported in part by a NRC/NIST-NIH Research Fellowship
(AB), NIST-ARRA Senior Fellowship (JER), and grants from the NIST Office
of Law Enforcement Standards (J.J.K, J.W.F.R., J.E.R.) and the NSF
(D.L.B.). We would like to thank Les Kirkegaard at BioAssay Works for
helpful discussions regarding the characteristics of the gold
nanoparticles, Arad Lajevardi-Khosh for sample preparation and SEM
counting statistics, and Andras Vladar, Bin Ming, and Premsagar Kavuri
for access to and assistance with SEM imaging.
NR 107
TC 26
Z9 26
U1 2
U2 29
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD FEB 27
PY 2013
VL 135
IS 8
BP 3087
EP 3094
DI 10.1021/ja309892e
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA 099KC
UT WOS:000315618900041
PM 23347384
ER
PT J
AU Davey, RT
Lynfield, R
Dwyer, DE
Losso, MH
Cozzi-Lepri, A
Wentworth, D
Lane, HC
Dewar, R
Rupert, A
Metcalf, JA
Pett, SL
Uyeki, TM
Bruguera, JM
Angus, B
Cummins, N
Lundgren, J
Neaton, JD
AF Davey, Richard T., Jr.
Lynfield, Ruth
Dwyer, Dominic E.
Losso, Marcello H.
Cozzi-Lepri, Alessandro
Wentworth, Deborah
Lane, H. Clifford
Dewar, Robin
Rupert, Adam
Metcalf, Julia A.
Pett, Sarah L.
Uyeki, Timothy M.
Maria Bruguera, Jose
Angus, Brian
Cummins, Nathan
Lundgren, Jens
Neaton, James D.
CA Insight FLU 002 Study Grp
Insight FLU 003 Study Grp
TI The Association between Serum Biomarkers and Disease Outcome in
Influenza A(H1N1)pdm09 Virus Infection: Results of Two International
Observational Cohort Studies
SO PLOS ONE
LA English
DT Article
ID PANDEMIC H1N1 2009; CYTOKINE RESPONSE; SEVERE PNEUMONIA; SURVEILLANCE;
PATHOGENESIS; ILLNESS
AB Background: Prospective studies establishing the temporal relationship between the degree of inflammation and human influenza disease progression are scarce. To assess predictors of disease progression among patients with influenza A(H1N1)pdm09 infection, 25 inflammatory biomarkers measured at enrollment were analyzed in two international observational cohort studies.
Methods: Among patients with RT-PCR-confirmed influenza A(H1N1) pdm09 virus infection, odds ratios (ORs) estimated by logistic regression were used to summarize the associations of biomarkers measured at enrollment with worsened disease outcome or death after 14 days of follow-up for those seeking outpatient care (FLU 002) or after 60 days for those hospitalized with influenza complications (FLU 003). Biomarkers that were significantly associated with progression in both studies (p<0.05) or only in one (p<0.002 after Bonferroni correction) were identified.
Results: In FLU 002 28/528 (5.3%) outpatients had influenza A(H1N1) pdm09 virus infection that progressed to a study endpoint of complications, hospitalization or death, whereas in FLU 003 28/170 (16.5%) inpatients enrolled from the general ward and 21/39 (53.8%) inpatients enrolled directly from the ICU experienced disease progression. Higher levels of 12 of the 25 markers were significantly associated with subsequent disease progression. Of these, 7 markers (IL-6, CD163, IL-10, LBP, IL-2, MCP-1, and IP-10), all with ORs for the 3rd versus 1st tertile of 2.5 or greater, were significant (p<0.05) in both outpatients and inpatients. In contrast, five markers (sICAM-1, IL-8, TNF-alpha, D-dimer, and sVCAM-1), all with ORs for the 3rd versus 1st tertile greater than 3.2, were significantly (p <=.002) associated with disease progression among hospitalized patients only.
Conclusions: In patients presenting with varying severities of influenza A(H1N1)pdm09 virus infection, a baseline elevation in several biomarkers associated with inflammation, coagulation, or immune function strongly predicted a higher risk of disease progression. It is conceivable that interventions designed to abrogate these baseline elevations might affect disease outcome.
C1 [Davey, Richard T., Jr.; Lane, H. Clifford; Metcalf, Julia A.] NIAID, NIH, Bethesda, MD 20892 USA.
[Lynfield, Ruth] Minnesota Dept Hlth, Div Infect Dis, St Paul, MN USA.
[Dwyer, Dominic E.] Westmead Hosp, Dept Virol, Ctr Infect Dis & Microbiol, Westmead, NSW 2145, Australia.
[Dwyer, Dominic E.] Univ Sydney, Westmead, NSW 2145, Australia.
[Losso, Marcello H.] Hosp Jose Maria Ramos Mejia, Dept Med, HIV Unit, Buenos Aires, DF, Argentina.
[Cozzi-Lepri, Alessandro] UCL, Res Dept Infect & Populat Hlth, London, England.
[Wentworth, Deborah; Neaton, James D.] Univ Minnesota, Div Biostat, Minneapolis, MN USA.
[Dewar, Robin] SAIC Frederick Inc, Frederick Natl Lab, Virus Isolat & Serol Lab, Frederick, MD USA.
[Rupert, Adam] SAIC Frederick Inc, AIDS Monitoring Lab, Frederick, MD USA.
[Pett, Sarah L.] Univ New S Wales, Fac Med, Kirby Inst, Sydney, NSW, Australia.
[Uyeki, Timothy M.] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA USA.
[Maria Bruguera, Jose] Hosp Jose Maria Ramos Mejia, Serv Inmunocomprometidos, Buenos Aires, DF, Argentina.
[Angus, Brian] Univ Oxford, Nuffield Dept Med, Oxford, England.
[Cummins, Nathan] Mayo Clin, Div Infect Dis, Rochester, MN USA.
[Lundgren, Jens] Rigshosp, Copenhagen Univ Hosp, Dept Infect Dis, DK-2100 Copenhagen, Denmark.
[Lundgren, Jens] Univ Copenhagen, Copenhagen, Denmark.
RP Davey, RT (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rdavey@niaid.nih.gov
RI Burgmann, Heinz/N-2409-2013; Emery, Sean/H-4920-2013;
OI Emery, Sean/0000-0001-6072-8309; Lundgren, Jens/0000-0001-8901-7850;
Angus, Brian/0000-0003-3598-7784
FU United States National Institutes of Health [UOI-AI068641];
SAIC-Frederick, Inc., NCI-Frederick, Maryland [HHSN261200800001E]
FX INSIGHT is funded by United States National Institutes of Health Grant
UOI-AI068641, and the FLU 002 and FLU 003 studies are partially funded
by SAIC-Frederick, Inc., Prime Contract HHSN261200800001E,
NCI-Frederick, Maryland 21702. Disclosure: The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 30
TC 11
Z9 11
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 FEB 27
PY 2013
VL 8
IS 2
AR e57121
DI 10.1371/journal.pone.0057121
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 098BN
UT WOS:000315519000064
PM 23468921
ER
PT J
AU Gotea, V
Petrykowska, HM
Elnitski, L
AF Gotea, Valer
Petrykowska, Hanna M.
Elnitski, Laura
TI Bidirectional Promoters as Important Drivers for the Emergence of
Species-Specific Transcripts
SO PLOS ONE
LA English
DT Article
ID LONG NONCODING RNAS; BIASED GENE CONVERSION; HUMAN GENOME; POSITIVE
SELECTION; FACTOR-BINDING; ALU REPEATS; EVOLUTION; DNA; VARIABILITY;
DROSOPHILA
AB The diversification of gene functions has been largely attributed to the process of gene duplication. Novel examples of genes originating from previously untranscribed regions have been recently described without regard to a unifying functional mechanism for their emergence. Here we propose a model mechanism that could generate a large number of lineage-specific novel transcripts in vertebrates through the activation of bidirectional transcription from unidirectional promoters. We examined this model in silico using human transcriptomic and genomic data and identified evidence consistent with the emergence of more than 1,000 primate-specific transcripts. These are transcripts with low coding potential and virtually no functional annotation. They initiate at less than 1 kb upstream of an oppositely transcribed conserved protein coding gene, in agreement with the generally accepted definition of bidirectional promoters. We found that the genomic regions upstream of ancestral promoters, where the novel transcripts in our dataset reside, are characterized by preferential accumulation of transposable elements. This enhances the sequence diversity of regions located upstream of ancestral promoters, further highlighting their evolutionary importance for the emergence of transcriptional novelties. By applying a newly developed test for positive selection to transposable element-derived fragments in our set of novel transcripts, we found evidence of adaptive evolution in the human lineage in nearly 3% of the novel transcripts in our dataset. These findings indicate that at least some novel transcripts could become functionally relevant, and thus highlight the evolutionary importance of promoters, through their capacity for bidirectional transcription, for the emergence of novel genes.
C1 [Gotea, Valer; Petrykowska, Hanna M.; Elnitski, Laura] NHGRI, DIR GTB Genom Funct Anal Sect, NIH, Bethesda, MD 20892 USA.
RP Elnitski, L (reprint author), NHGRI, DIR GTB Genom Funct Anal Sect, NIH, Bethesda, MD 20892 USA.
EM elnitski@mail.nih.gov
OI Gotea, Valer/0000-0001-7857-3309
FU Intramural program of the National Human Genome Research Institute,
National Institutes of Health
FX This work was supported by the Intramural program of the National Human
Genome Research Institute, National Institutes of Health. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 54
TC 14
Z9 14
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 FEB 27
PY 2013
VL 8
IS 2
AR e57323
DI 10.1371/journal.pone.0057323
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 098BN
UT WOS:000315519000092
PM 23460838
ER
PT J
AU James, MM
Laeyendecker, O
Sun, J
Hoover, DR
Mullis, CE
Cousins, MM
Coates, T
Moore, RD
Kelen, GD
Fowler, MG
Kumwenda, JJ
Mofenson, LM
Kumwenda, NI
Taha, TE
Eshleman, SH
AF James, Maria M.
Laeyendecker, Oliver
Sun, Jin
Hoover, Donald R.
Mullis, Caroline E.
Cousins, Matthew M.
Coates, Thomas
Moore, Richard D.
Kelen, Gabor D.
Fowler, Mary Glenn
Kumwenda, Johnstone J.
Mofenson, Lynne M.
Kumwenda, Newton I.
Taha, Taha E.
Eshleman, Susan H.
TI Antibody Maturation and Viral Diversification in HIV-Infected Women
SO PLOS ONE
LA English
DT Article
ID RESOLUTION MELTING ASSAY; ENZYME-IMMUNOASSAY; DRUG-RESISTANCE;
SUBTYPE-C; DIVERSITY; TRANSMISSION; MUTATIONS; AFRICA; SEX
AB Introduction: The Post-exposure Prophylaxis in Infants (PEPI)-Malawi trial evaluated infant antiretroviral regimens for prevention of post-natal HIV transmission. A multi-assay algorithm (MAA) that includes the BED capture immunoassay, an avidity assay, CD4 cell count, and viral load was used to identify women who were vs. were not recently infected at the time of enrollment (MAA recent, N = 73; MAA non-recent, N = 2,488); a subset of the women in the MAA non-recent group known to have been HIV infected for at least 2 years before enrollment (known non-recent, N = 54). Antibody maturation and viral diversification were examined in these women.
Methods: Samples collected at enrollment (N = 2,561) and 12-24 months later (N = 1,306) were available for serologic analysis using the BED and avidity assays. A subset of those samples was used for analysis of viral diversity, which was performed using a high resolution melting (HRM) diversity assay. Viral diversity analysis was performed using all available samples from women in the MAA recent group (61 enrollment samples, 38 follow-up samples) and the known non-recent group (43 enrollment samples, 22 follow-up samples). Diversity data from PEPI-Malawi were also compared to similar data from 169 adults in the United States (US) with known recent infection (N = 102) and known non-recent infection (N = 67).
Results: In PEPI-Malawi, results from the BED and avidity assays increased over time in the MAA recent group, but did not change significantly in the MAA non- recent group. At enrollment, HIV diversity was lower in the MAA recent group than in the known non- recent group. HRM diversity assay results from women in PEPI-Malawi were similar to those from adults in the US with known duration of HIV infection.
Conclusions: Antibody maturation and HIV diversification patterns in African women provide additional support for use of the MAA to identify populations with recent HIV infection.
C1 [James, Maria M.; Cousins, Matthew M.; Fowler, Mary Glenn; Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Laeyendecker, Oliver] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Laeyendecker, Oliver; Mullis, Caroline E.; Moore, Richard D.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Sun, Jin; Kumwenda, Newton I.; Taha, Taha E.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Hoover, Donald R.] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA.
[Hoover, Donald R.] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, Piscataway, NJ USA.
[Coates, Thomas] Univ Calif Los Angeles, Program Global Hlth, Los Angeles, CA USA.
[Kelen, Gabor D.] Johns Hopkins Univ, Sch Med, Dept Emergency Med, Baltimore, MD USA.
[Kumwenda, Johnstone J.] Univ Malawi, Dept Med, Coll Med, Blantyre, Malawi.
[Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA.
RP Eshleman, SH (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
EM seshlem@jhmi.edu
RI Laeyendecker, Oliver/B-9331-2009;
OI Mofenson, Lynne/0000-0002-2818-9808; Kelen, Gabor/0000-0002-3236-8286;
Laeyendecker, Oliver/0000-0002-6429-4760
FU International Maternal Pediatric Adolescent AIDS Clinical Trials
(IMPAACT) Group, American Recovery and Reinvestment Act (ARRA) award
[3U01AI068632-05S3]; National Institute of Allergy and Infectious
Diseases (NIAID); National Institute on Drug Abuse (NIDA); National
Institute of Mental Health (NIMH); Office of AIDS Research, of the
National Institutes of Health (NIH), Dept. of Health and Human Services
(DHHS) [U01AI068613, UM1AI068613]; Centers for Disease Control and
Prevention [U50/CCU022061]; International Maternal Pediatric and
Adolescent AIDS Clinical Trials (IMPAACT) Group [U01-AI068632]
FX Funders for this work are as follows: (1) International Maternal
Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group, American
Recovery and Reinvestment Act (ARRA) award (Cooperative Agreement
3U01AI068632-05S3); (2) The HIV Prevention Trials Network (HPTN)
sponsored by the National Institute of Allergy and Infectious Diseases
(NIAID), the National Institute on Drug Abuse (NIDA), the National
Institute of Mental Health (NIMH), and the Office of AIDS Research, of
the National Institutes of Health (NIH), Dept. of Health and Human
Services (DHHS) (U01AI068613, UM1AI068613); (3) The Centers for Disease
Control and Prevention (Cooperative Agreement U50/CCU022061); and (4)
The International Maternal Pediatric and Adolescent AIDS Clinical Trials
(IMPAACT) Group (U01-AI068632). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 28
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U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 27
PY 2013
VL 8
IS 2
AR e57350
DI 10.1371/journal.pone.0057350
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 098BN
UT WOS:000315519000096
PM 23460842
ER
PT J
AU Ma, LJ
Murea, M
Snipes, JA
Marinelarena, A
Kruger, J
Hicks, PJ
Langberg, KA
Bostrom, MA
Cooke, JN
Suzuki, D
Babazono, T
Uzu, T
Tang, SCW
Mondal, AK
Sharma, NK
Kobes, S
Antinozzi, PA
Davis, M
Das, SK
Rasouli, N
Kern, PA
Shores, NJ
Rudel, LL
Bluuher, M
Stumvoll, M
Bowden, DW
Maeda, S
Parks, JS
Kovacs, P
Hanson, RL
Baier, LJ
Elbein, SC
Freedman, BI
AF Ma, Lijun
Murea, Mariana
Snipes, James A.
Marinelarena, Alejandra
Krueger, Jacqueline
Hicks, Pamela J.
Langberg, Kurt A.
Bostrom, Meredith A.
Cooke, Jessica N.
Suzuki, Daisuke
Babazono, Tetsuya
Uzu, Takashi
Tang, Sydney C. W.
Mondal, Ashis K.
Sharma, Neeraj K.
Kobes, Sayuko
Antinozzi, Peter A.
Davis, Matthew
Das, Swapan K.
Rasouli, Neda
Kern, Philip A.
Shores, Nathan J.
Rudel, Lawrence L.
Blueher, Matthias
Stumvoll, Michael
Bowden, Donald W.
Maeda, Shiro
Parks, John S.
Kovacs, Peter
Hanson, Robert L.
Baier, Leslie J.
Elbein, Steven C.
Freedman, Barry I.
TI An ACACB Variant Implicated in Diabetic Nephropathy Associates with Body
Mass Index and Gene Expression in Obese Subjects
SO PLOS ONE
LA English
DT Article
ID ACETYL-COA CARBOXYLASE-2; FATTY-ACID OXIDATION; ADIPOSE-TISSUE; MICE
LACKING; MUTANT MICE; POLYMORPHISMS; METABOLISM; DIET; KNOCKOUT; GLUCOSE
AB Acetyl coenzyme A carboxylase B gene (ACACB) single nucleotide polymorphism (SNP) rs2268388 is reproducibly associated with type 2 diabetes (T2DM)-associated nephropathy (DN). ACACB knock-out mice are also protected from obesity. This study assessed relationships between rs2268388, body mass index (BMI) and gene expression in multiple populations, with and without T2DM. Among subjects without T2DM, rs2268388 DN risk allele (T) associated with higher BMI in Pima Indian children (n = 2021; p-additive = 0.029) and African Americans (AAs) (n = 177; p-additive = 0.05), with a trend in European Americans (EAs) (n = 512; p-additive = 0.09), but not Germans (n = 858; p-additive = 0.765). Association with BMI was seen in a meta-analysis including all non-T2DM subjects (n = 3568; p-additive = 0.02). Among subjects with T2DM, rs2268388 was not associated with BMI in Japanese (n = 2912) or EAs (n = 1149); however, the T allele associated with higher BMI in the subset with BMI >= 30 kg/m(2) (n = 568 EAs; p-additive = 0.049, n = 196 Japanese; p-additive = 0.049). Association with BMI was strengthened in a T2DM meta-analysis that included an additional 756 AAs (p-additive = 0.080) and 48 Hong Kong Chinese (p-additive = 0.81) with BMI >= 30 kg/m(2) (n = 1575; p-additive = 0.0033). The effect of rs2268388 on gene expression revealed that the T risk allele associated with higher ACACB messenger levels in adipose tissue (41 EAs and 20 AAs with BMI > 30 kg/m(2); p-additive = 0.018) and ACACB protein levels in the liver tissue (mixed model p-additive = 0.03, in 25 EA bariatric surgery patients with BMI > 30 kg/m(2) for 75 exams). The T allele also associated with higher hepatic triglyceride levels. These data support a role for ACACB in obesity and potential roles for altered lipid metabolism in susceptibility to DN.
C1 [Ma, Lijun; Murea, Mariana; Snipes, James A.; Hicks, Pamela J.; Langberg, Kurt A.; Bostrom, Meredith A.; Cooke, Jessica N.; Mondal, Ashis K.; Sharma, Neeraj K.; Antinozzi, Peter A.; Davis, Matthew; Das, Swapan K.; Shores, Nathan J.; Rudel, Lawrence L.; Bowden, Donald W.; Parks, John S.; Elbein, Steven C.; Freedman, Barry I.] Wake Forest Sch Med, Winston Salem, NC USA.
[Marinelarena, Alejandra; Kobes, Sayuko; Hanson, Robert L.; Baier, Leslie J.] NIDDKD, PECRB, Phoenix, AZ USA.
[Krueger, Jacqueline; Blueher, Matthias; Stumvoll, Michael; Kovacs, Peter] Univ Leipzig, Interdisciplinary Ctr Clin Res, D-04109 Leipzig, Germany.
[Suzuki, Daisuke] Tokai Univ, Div Nephrol & Metab, Dept Internal Med, Tokyo 151, Japan.
[Babazono, Tetsuya] Tokyo Womens Med Univ, Ctr Diabet, Tokyo, Japan.
[Uzu, Takashi] Shiga Univ Med Sci, Dept Med, Otsu, Shiga 52021, Japan.
[Tang, Sydney C. W.] Univ Hong Kong, Dept Internal Med, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China.
[Rasouli, Neda] Univ Colorado, Dept Internal Med, Sch Med, Aurora, CO USA.
[Kern, Philip A.] Univ Kentucky, Coll Med, Dept Internal Med, Lexington, KY USA.
[Shores, Nathan J.] Tulane Univ Med Ctr Hosp & Clin, Abdominal Transplant Inst, New Orleans, LA USA.
[Maeda, Shiro] RIKEN, Ctr Genom Med, Lab Endocrinol & Metab, Yokohama, Kanagawa, Japan.
RP Ma, LJ (reprint author), Wake Forest Sch Med, Winston Salem, NC USA.
EM lima@wakehealth.edu
RI Hanson, Robert/O-3238-2015
OI Hanson, Robert/0000-0002-4252-7068
FU Wake Forest School of Medicine Translational Science Institute Synergy
Grant [K99 DK081350]; National Institutes of Health [R01 DK071891, R01
HL67348, R01 DK53591, R01 DK039311]; Veterans Administration; NIDDK;
Ministry of Education, Culture, Sports, Science and Technology, Japan;
Boehringer Ingelheim Foundation; [R0171349]
FX This study was supported by a Wake Forest School of Medicine
Translational Science Institute Synergy Grant K99 DK081350, National
Institutes of Health extramural grants R01 DK071891, R01 HL67348, R01
DK53591, R01 DK039311, and partially supported by R0171349, a Merit
Grant from the Veterans Administration, and NIDDK intramural research
program. The Japanese study was partly supported by a grant from the
Ministry of Education, Culture, Sports, Science and Technology, Japan
(S. M.). P. K. (Leipzig) was funded by Boehringer Ingelheim Foundation.
The funders 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 1
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 FEB 27
PY 2013
VL 8
IS 2
AR e56193
DI 10.1371/journal.pone.0056193
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 098BN
UT WOS:000315519000017
PM 23460794
ER
PT J
AU Moustafa, ME
Carlson, BA
Anver, MR
Bobe, G
Zhong, NX
Ward, JM
Perella, CM
Hoffmann, VJ
Rogers, K
Combs, GF
Schweizer, U
Merlino, G
Gladyshev, VN
Hatfield, DL
AF Moustafa, Mohamed E.
Carlson, Bradley A.
Anver, Miriam R.
Bobe, Gerd
Zhong, Nianxin
Ward, Jerrold M.
Perella, Christine M.
Hoffmann, Victoria J.
Rogers, Keith
Combs, Gerald F., Jr.
Schweizer, Ulrich
Merlino, Glenn
Gladyshev, Vadim N.
Hatfield, Dolph L.
TI Selenium and Selenoprotein Deficiencies Induce Widespread Pyogranuloma
Formation in Mice, while High Levels of Dietary Selenium Decrease Liver
Tumor Size Driven by TGF alpha
SO PLOS ONE
LA English
DT Article
ID SELENOCYSTEINE TRANSFER-RNA; TRANSGENIC MICE; MAMMALIAN-CELLS;
EXPRESSION; MOUSE; CANCER; HEPATOCARCINOGENESIS; INFLAMMATION;
POPULATION; DELETION
AB Changes in dietary selenium and selenoprotein status may influence both anti- and pro-cancer pathways, making the outcome of interventions different from one study to another. To characterize such outcomes in a defined setting, we undertook a controlled hepatocarcinogenesis study involving varying levels of dietary selenium and altered selenoprotein status using mice carrying a mutant (A37G) selenocysteine tRNA transgene (Trsp(tG37)) and/or a cancer driver TGF alpha transgene. The use of Trsp(tG37) altered selenoprotein expression in a selenoprotein and tissue specific manner and, at sufficient dietary selenium levels, separate the effect of diet and selenoprotein status. Mice were maintained on diets deficient in selenium (0.02 ppm selenium) or supplemented with 0.1, 0.4 or 2.25 ppm selenium or 30 ppm triphenylselenonium chloride (TPSC), a non-metabolized selenium compound. Trsp(tG37) transgenic and TGF alpha/Trsp(tG37) bi-transgenic mice subjected to selenium-deficient or TPSC diets developed a neurological phenotype associated with early morbidity and mortality prior to hepatocarcinoma development. Pathology analyses revealed widespread disseminated pyogranulomatous inflammation. Pyogranulomas occurred in liver, lungs, heart, spleen, small and large intestine, and mesenteric lymph nodes in these transgenic and bi-transgenic mice. The incidence of liver tumors was significantly increased in mice carrying the TGF alpha transgene, while dietary selenium and selenoprotein status did not affect tumor number and multiplicity. However, adenoma and carcinoma size and area were smaller in TGF alpha transgenic mice that were fed 0.4 and 2.25 versus 0.1 ppm of selenium. Thus, selenium and selenoprotein deficiencies led to widespread pyogranuloma formation, while high selenium levels inhibited the size of TGF alpha-induced liver tumors.
C1 [Moustafa, Mohamed E.; Carlson, Bradley A.; Zhong, Nianxin; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, NIH, Bethesda, MD 20892 USA.
[Anver, Miriam R.; Rogers, Keith] Sci Applicat Int Corp Frederick Inc, Pathol Histotechnol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Bobe, Gerd] Oregon State Univ, Dept Anim & Rangeland Sci, Coll Agr, Corvallis, OR 97331 USA.
[Bobe, Gerd] Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA.
[Ward, Jerrold M.] NIAID, Immunopathol Sect, NIH, Bethesda, MD 20892 USA.
[Perella, Christine M.] Sci Applicat Int Corp Frederick Inc, Lab Anim Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Hoffmann, Victoria J.] NCI, Off Director, Diagnost & Res Serv Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Combs, Gerald F., Jr.] USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA.
[Schweizer, Ulrich] Charite, Inst Expt Endokrinol, D-13353 Berlin, Germany.
[Merlino, Glenn] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA USA.
RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, NIH, Bethesda, MD 20892 USA.
EM hatfield@dc37a.nci.nih.gov
RI Gladyshev, Vadim/A-9894-2013; Schweizer, Ulrich/E-8105-2013
FU Intramural Research Program of the National Institutes of Health (NIH);
National Cancer Institute; Center for Cancer Research; NIH; National
Cancer Institute, National Institutes of Health [HHSN261200800001E]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research to DLH, NIH grants to VNG and the National Cancer
Institute, National Institutes of Health, under Contract No.
HHSN261200800001E. The authors express their sincere appreciation to
BAC, R. Irons and C. D. Davis who made the video shown in the Online
Supplementary Information in DLH's laboratory. 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
U.S. Government. 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 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 FEB 27
PY 2013
VL 8
IS 2
AR e57389
DI 10.1371/journal.pone.0057389
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 098BN
UT WOS:000315519000101
PM 23460847
ER
PT J
AU Waltz, JA
Kasanova, Z
Ross, TJ
Salmeron, BJ
McMahon, RP
Gold, JM
Stein, EA
AF Waltz, James A.
Kasanova, Zuzana
Ross, Thomas J.
Salmeron, Betty J.
McMahon, Robert P.
Gold, James M.
Stein, Elliot A.
TI The Roles of Reward, Default, and Executive Control Networks in
Set-Shifting Impairments in Schizophrenia
SO PLOS ONE
LA English
DT Article
ID TEMPORAL DIFFERENCE MODELS; PREFRONTAL CORTEX; BRAIN NETWORKS;
FUNCTIONAL CONNECTIVITY; CINGULATE CORTEX; DECISION-MAKING;
RATING-SCALE; DYSFUNCTION; REPRESENTATION; COGNITION
AB Patients with schizophrenia (SZ) show deficits on tasks of rapid reinforcement learning, like probabilistic reversal learning (PRL), but the neural bases for those impairments are not known. Recent evidence of relatively intact sensitivity to negative outcomes in the ventral striatum (VS) in many SZ patients suggests that PRL deficits may be largely attributable to processes downstream from feedback processing, involving both the activation of executive control task regions and deactivation of default mode network (DMN) components. We analyzed data from 29 chronic SZ patients and 21 matched normal controls (NCs) performing a PRL task in an MRI scanner. Subjects were presented with eight pairs of fractal stimuli, for 50 trials each. For each pair, subjects learned to choose the more frequently-rewarded (better) stimulus. Each time a criterion was reached, the better stimulus became the worse one, and the worse became the better. Responses to feedback events were assessed through whole-brain and regions-of-interest (ROI) analyses in DMN. We also assessed correlations between BOLD signal contrasts and clinical measures in SZs. Relative to NCs, SZ patients showed comparable deactivation of VS in response to negative feedback, but reduced deactivation of DMN components including medial prefrontal cortex (mPFC). The magnitudes of patients' punishment-evoked deactivations in VS and ventromedial PFC correlated significantly with clinical ratings for avolition/anhedonia. These findings suggest that schizophrenia is associated with a reduced ability to deactivate components of default mode networks, following the presentation of informative feedback and that motivational deficits in SZ relate closely to feedback-evoked activity in reward circuit components. These results also confirm a role for ventrolateral and dorsomedial PFC in the execution of response-set shifts.
C1 [Waltz, James A.; Kasanova, Zuzana; McMahon, Robert P.; Gold, James M.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA.
[Ross, Thomas J.; Salmeron, Betty J.; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD USA.
RP Waltz, JA (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA.
EM jwaltz@mprc.umaryland.edu
RI McMahon, Robert/C-5462-2009; Salmeron, Betty Jo/M-1793-2016;
OI Salmeron, Betty Jo/0000-0003-1699-9333; Kasanova,
Zuzana/0000-0002-8795-5373; Ross, Thomas/0000-0002-7745-3572
FU National Institutes of Health (NIH) [K12 RR023250, R01 MH080066];
National Institute on Drug Abuse - Intramural Research Program
(NIDA-IRP); [HHSN271200599091C/ADB]; [N01DA-5-9909]
FX This work supported by National Institutes of Health (NIH) grants K12
RR023250, R01 MH080066, a project grant from HHSN271200599091C/ADB
Contract # N01DA-5-9909 and by the National Institute on Drug Abuse -
Intramural Research Program (NIDA-IRP). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 70
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U1 5
U2 20
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 27
PY 2013
VL 8
IS 2
AR e57257
DI 10.1371/journal.pone.0057257
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 098BN
UT WOS:000315519000084
PM 23468948
ER
PT J
AU Evsen, L
Sugahara, S
Uchikawa, M
Kondoh, H
Wu, DK
AF Evsen, Lale
Sugahara, Satoko
Uchikawa, Masanori
Kondoh, Hisato
Wu, Doris K.
TI Progression of Neurogenesis in the Inner Ear Requires Inhibition of Sox2
Transcription by Neurogenin1 and Neurod1
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID SENSORY ORGAN GENERATION; NEURAL STEM-CELLS; XENOPUS RETINA;
CHICK-EMBRYO; HAIR-CELLS; GENE; DIFFERENTIATION; EXPRESSION; EPITHELIA;
FATE
AB Sox2 is required for proper neuronal formation in the CNS, but the molecular mechanisms involved are not well characterized. Here, we addressed the role of Sox2 in neurogenesis of the developing chicken inner ear. Overexpressing Sox2 from a constitutive (beta-actin) promoter induces the expression of the proneural gene, Neurogenin1 (Ngn1); however, the expression of a downstream target of Ngn1, Neurod1, is unchanged. As a result, there is a reduction of neural precursors to delaminate and populate the developing cochleovestibular ganglion. In contrast, overexpression of either Ngn1 or Neurod1 is sufficient to promote the neural fate in this system. These results suggest that high levels of Sox2 inhibit progression of neurogenesis in the developing inner ear. Furthermore, we provide evidence that Ngn1 and Neurod1 inhibit Sox2 transcription through a phylogenetically conserved Sox2 enhancer to mediate neurogenesis. We propose that Sox2 confers neural competency by promoting Ngn1 expression, and that negative feedback inhibition of Sox2 by Ngn1 is an essential step in the progression from neural precursor to nascent neuron.
C1 [Evsen, Lale; Wu, Doris K.] Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA.
[Sugahara, Satoko; Uchikawa, Masanori; Kondoh, Hisato] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan.
[Evsen, Lale] Univ Maryland, Neurosci & Cognit Sci Program, College Pk, MD 20740 USA.
RP Wu, DK (reprint author), NIDCD 5 Res Court,Room 2B34, Rockville, MD 20850 USA.
EM wud@nidcd.nih.gov
FU Intramural Program of NIDCD; MEXT Japan [22247035]; [23770248]
FX This work was supported by the Intramural Program of NIDCD (to D.K.W.),
Grants-in-Aid for Scientific Research 23770248 (to M.U.) and MEXT Japan
22247035 (to H.K.). We thank Michael Mulheisen, Nicole Huang, Nathan
Hsieh, Eric Yi, and Andrew Yatteau for technical assistance. We thank
Dr. Lisa Taneyhill at the University of Maryland at College Park for
valuable advice throughout this project, Dr. Jonas Muhr for providing
the Sox2 plasmid, Dr. Jean-Marc Matter for the Neurod1 plasmid, and Dr.
Marianne Bronner-Fraser for the pCI-IRES-H2B-RFP plasmid. We also thank
Drs. Lisa Cunningham, Tom Friedman, Matthew Kelley, James Keller, and
Steven Raft for critical reading of this manuscript.
NR 47
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U1 0
U2 4
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 FEB 27
PY 2013
VL 33
IS 9
BP 3879
EP 3890
DI 10.1523/JNEUROSCI.4030-12.2013
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 098ZO
UT WOS:000315588000016
PM 23447599
ER
PT J
AU Izquierdo, A
Darling, C
Manos, N
Pozos, H
Kim, C
Ostrander, S
Cazares, V
Stepp, H
Rudebeck, PH
AF Izquierdo, Alicia
Darling, Chelsi
Manos, Nic
Pozos, Hilda
Kim, Charissa
Ostrander, Serena
Cazares, Victor
Stepp, Haley
Rudebeck, Peter H.
TI Basolateral Amygdala Lesions Facilitate Reward Choices after Negative
Feedback in Rats
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ORBITOFRONTAL CORTEX; PREFRONTAL CORTEX; FRONTAL-CORTEX; REVERSAL; MICE;
MONKEYS; DISCRIMINATION; IMPAIRMENTS; STIMULI; MODELS
AB The orbitofrontal cortex (OFC) and basolateral amygdala (BLA) constitute part of a neural circuit important for adaptive, goal-directed learning. One task measuring flexibility of response to changes in reward is discrimination reversal learning. Damage to OFC produces well documented impairments on various forms of reversal learning in rodents, monkeys, and humans. Recent reports show that BLA, though highly interconnected with OFC, may be differentially involved in reversal learning. In the present experiment, we compared the effects of bilateral, ibotenic acid lesions of OFC or BLA (or SHAM) on visual discrimination and reversal learning. Specifically, we used pairwise visual discrimination methods, as is commonly administered in non-human primate studies, and analyzed how animals use positive and negative trial-by-trial feedback, domains not previously explored in a rat study. As expected, OFC lesions displayed significantly slower reversal learning than SHAM and BLA rats across sessions. Rats with BLA lesions, conversely, showed facilitated reversal learning relative to SHAM and OFC groups. Furthermore, a trial-by-trial analysis of the errors committed showed the BLA group benefited more from incorrectly performed trials (or negative feedback) on future choices than either SHAM or OFC rats. This provides evidence that BLA and OFC are involved in updating responses to changes in reward contingency and that the roles are distinct. Our results are discussed in relation to a competitive framework model for OFC and BLA in reward processing.
C1 [Izquierdo, Alicia; Darling, Chelsi; Manos, Nic; Pozos, Hilda; Kim, Charissa; Ostrander, Serena; Cazares, Victor; Stepp, Haley] Calif State Univ Los Angeles, Dept Psychol, Cognit Neurosci Lab, Los Angeles, CA 90032 USA.
[Rudebeck, Peter H.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP Izquierdo, A (reprint author), Calif State Univ Los Angeles, 5151 State Univ Dr, Los Angeles, CA 90032 USA.
EM aizquie@calstatela.edu
OI Rudebeck, Peter/0000-0002-1411-7555; Kim, Charissa/0000-0003-4899-5898
FU NIH Minority Biomedical Research Support program at California State
University, Los Angeles (CSULA); NIMH [SC2MH087974-03]
FX This work was supported by the NIH Minority Biomedical Research Support
program at California State University, Los Angeles (CSULA). Partial
support also came from NIMH (Grant SC2MH087974-03, to A.I.). We thank
the CSULA Animal Care staff and the Russo-Neustadt and de Leon labs for
technical support.
NR 27
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U1 1
U2 9
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 FEB 27
PY 2013
VL 33
IS 9
BP 4105
EP +
DI 10.1523/JNEUROSCI.4942-12.2013
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 098ZO
UT WOS:000315588000035
PM 23447618
ER
PT J
AU Birdsong, WT
Arttamangkul, S
Clark, MJ
Cheng, KJ
Rice, KC
Traynor, JR
Williams, JT
AF Birdsong, William T.
Arttamangkul, Seksiri
Clark, Mary J.
Cheng, Kejun
Rice, Kenner C.
Traynor, John R.
Williams, John T.
TI Increased Agonist Affinity at the mu-Opioid Receptor Induced by
Prolonged Agonist Exposure
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID BETA-ADRENERGIC-RECEPTOR; LOCUS-CERULEUS NEURONS; CONFORMATIONAL STATES;
BINDING-PROPERTIES; KINETIC EVIDENCE; PERTUSSIS TOXIN; DESENSITIZATION;
PROTEIN; MORPHINE; PHOSPHORYLATION
AB Prolonged exposure to high-efficacy agonists results in desensitization of the mu-opioid receptor (MOR). Desensitized receptors are thought to be unable to couple to G-proteins, preventing downstream signaling; however, the changes to the receptor itself are not well characterized. In the current study, confocal imaging was used to determine whether desensitizing conditions cause a change in agonist-receptor interactions. Using rapid solution exchange, the binding kinetics of fluorescently labeled opioid agonist, dermorphin Alexa594 (derm A594), to MORs was measured in live cells. The affinity of derm A594 binding increased after prolonged treatment of cells with multiple agonists that are known to cause receptor desensitization. In contrast, binding of a fluorescent antagonist, naltrexamine Alexa594, was unaffected by similar agonist pretreatment. The increased affinity of derm A594 for the receptor was long-lived and partially reversed after a 45 min wash. Treatment of the cells with pertussis toxin did not alter the increase in affinity of the derm A594 for MOR. Likewise, the affinity of derm A594 for MORs expressed in mouse embryonic fibroblasts derived from arrestin 1 and 2 knock-out animals increased after treatment of the cells with the desensitization protocol. Thus, opioid receptors were "imprinted" with a memory of prior agonist exposure that was independent of G-protein activation or arrestin binding that altered subsequent agonist-receptor interactions. The increased affinity suggests that acute desensitization results in a long-lasting but reversible conformational change in the receptor.
C1 [Birdsong, William T.; Arttamangkul, Seksiri; Williams, John T.] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
[Clark, Mary J.; Traynor, John R.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Cheng, Kejun; Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Cheng, Kejun; Rice, Kenner C.] NIAAA, NIH, Bethesda, MD 20892 USA.
RP Williams, JT (reprint author), Oregon Hlth & Sci Univ, Vollum Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM williamj@ohsu.edu
FU National Institutes of Health [DA08136, MH083754]; Intramural Research
Programs of National Institute on Drug Abuse and National Institute on
Alcohol Abuse and Alcoholism
FX This work was supported by National Institutes of Health Grants DA08136
and MH083754 to J.R.T. and M.J.C., and in part by the Intramural
Research Programs of National Institute on Drug Abuse and National
Institute on Alcohol Abuse and Alcoholism. We thank Dr. Shane Hentges
for feedback during manuscript preparation, Dr. Erica Levitt for
manuscript feedback and GraphPad expertise, and Dr. Dale Fortin for
technical assistance.
NR 42
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U1 0
U2 13
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 FEB 27
PY 2013
VL 33
IS 9
BP 4118
EP 4127
DI 10.1523/JNEUROSCI.4187-12.2013
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 098ZO
UT WOS:000315588000037
PM 23447620
ER
PT J
AU Balaban, RS
AF Balaban, Robert S.
TI Allometry of brain metabolism
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID MITOCHONDRIAL; TISSUE
C1 NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA.
RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA.
EM balabanr@nhlbi.nih.gov
NR 18
TC 4
Z9 4
U1 5
U2 12
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 26
PY 2013
VL 110
IS 9
BP 3216
EP 3217
DI 10.1073/pnas.1221313110
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 102JW
UT WOS:000315841900010
PM 23407170
ER
PT J
AU Sivan, G
Martin, SE
Myers, TG
Buehler, E
Szymczyk, KH
Ormanoglu, P
Moss, B
AF Sivan, Gilad
Martin, Scott E.
Myers, Timothy G.
Buehler, Eugen
Szymczyk, Krysia H.
Ormanoglu, Pinar
Moss, Bernard
TI Human genome-wide RNAi screen reveals a role for nuclear pore proteins
in poxvirus morphogenesis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE nucleoporin 62; poxvirus replication; poxvirus host interactions;
syntaxin 5; vaccinia virus replication
ID VACCINIA VIRUS-REPLICATION; BINDING PROTEIN; CELL-MEMBRANE; HOST-CELLS;
INFECTION; TRANSPORT; COMPLEX; GENE; INTERMEDIATE; REQUIREMENT
AB Poxviruses are considered less dependent on host functions than other DNA viruses because of their cytoplasmic site of replication and large genomes, which encode enzymes for DNA and mRNA synthesis. Nevertheless, RNAi screens with two independent human genome-scale libraries have identified more than 500 candidate genes that significantly inhibited and a similar number that enhanced replication and spread of infectious vaccinia virus.(VACV). Translational, ubiquitin-proteosome, and endoplasmic reticulum-to-Golgi transport functions, known to be important for VACV, were enriched in the siRNA-inhibiting group, and RNA polymerase II and associated functions were enriched in the siRNA-enhancing group. Additional findings, notably the inhibition of VACV spread by siRNAs to several nuclear pore genes, were unanticipated. Knockdown of nucleoporin 62 strongly inhibited viral morphogenesis, with only a modest effect on viral gene expression, recapitulating and providing insight into previous studies with enucleated cells.
C1 [Sivan, Gilad; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Martin, Scott E.; Buehler, Eugen; Ormanoglu, Pinar] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Myers, Timothy G.; Szymczyk, Krysia H.] NIAID, Genom Technol Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM bmoss@niaid.nih.gov
OI Buehler, Eugen/0000-0001-7167-676X
FU Division of Intramural Research, NIAID, National Institutes of Health
FX We thank Elizabeth Fischer [National Institute of Allergy and Infectious
Diseases (NIAID) Rocky Mountain Electron Microscopy Laboratory] for
providing EM images and Catherine Cotter (MAID Laboratory of Viral
Diseases) for assisting with tissue cultures. This research was
supported by the Division of Intramural Research, NIAID, National
Institutes of Health.
NR 43
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U1 0
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 26
PY 2013
VL 110
IS 9
BP 3519
EP 3524
DI 10.1073/pnas.1300708110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 102JW
UT WOS:000315841900065
PM 23401514
ER
PT J
AU Daszak, P
Zambrana-Torrelio, C
Bogich, TL
Fernandez, M
Epstein, JH
Murray, KA
Hamilton, H
AF Daszak, Peter
Zambrana-Torrelio, Carlos
Bogich, Tiffany L.
Fernandez, Miguel
Epstein, Jonathan H.
Murray, Kris A.
Hamilton, Healy
TI Interdisciplinary approaches to understanding disease emergence: The
past, present, and future drivers of Nipah virus emergence
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID WEST NILE VIRUS; EMERGING INFECTIOUS-DISEASES; SPECIES DISTRIBUTION
MODELS; ECOLOGICAL NICHE MODELS; AVIAN INFLUENZA H5N1; CLIMATE-CHANGE;
FLYING-FOXES; UNITED-STATES; VECTOR-BORNE; FRUIT BATS
AB Emerging infectious diseases (EIDs) pose a significant threat to human health, economic stability, and biodiversity. Despite this, the mechanisms underlying disease emergence are still not fully understood, and control measures rely heavily on mitigating the impact of EIDs after they have emerged. Here, we highlight the emergence of a zoonotic Henipavirus, Nipah virus, to demonstrate the interdisciplinary and macroecological approaches necessary to understand EID emergence. Previous work suggests that Nipah virus emerged due to the interaction of the wildlife reservoir (Pteropus spp. fruit bats) with intensively Managed livestock. The emergence of this and other henipaviruses involves interactions among a suite of anthropogenic environmental changes, socioeconomic factors, and changes in demography that overlay and interact with the distribution of these pathogens in their wildlife reservoirs. Here, we demonstrate how ecological niche modeling may be used to investigate the potential role of a changing climate on the future risk for Henipavirus emergence. We show that the distribution of Henipavirus reservoirs, and therefore henipaviruses, will likely change under climate change scenarios, a fundamental precondition for disease emergence in humans. We assess the variation among climate models to estimate where Henipavirus host distribution is most likely to expand, contract, or remain stable, presenting new risks for human health. We conclude that there is substantial potential to use this modeling framework to explore the distribution of wildlife hosts under a changing climate. These approaches may directly inform current and future management and surveillance strategies aiming to improve pathogen detection and, ultimately, reduce emergence risk.
C1 [Daszak, Peter; Zambrana-Torrelio, Carlos; Bogich, Tiffany L.; Epstein, Jonathan H.; Murray, Kris A.] EcoHlth Alliance, New York, NY 10001 USA.
[Bogich, Tiffany L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Bogich, Tiffany L.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Fernandez, Miguel] Univ Calif, Environm Syst Grad Grp, Merced, CA 95344 USA.
[Hamilton, Healy] Marine Conservat Inst, Glen Ellen, CA 95442 USA.
RP Daszak, P (reprint author), EcoHlth Alliance, New York, NY 10001 USA.
EM daszak@ecohealthalliance.org
OI Bogich, Tiffany/0000-0002-8143-5289
FU National Institutes of Health/National Science Foundation "Ecology and
Evolution of Infectious Diseases" award from the Fogarty International
Center [2R01-TW005869]; National Institute of Allergy and Infectious
Diseases [1 R01 AI079231]; National Science Foundation Human and Social
Dynamics Agents of Change [BCS 0826779, BCS 0826840]; Research and
Policy for Infectious Disease Dynamics program of the Science and
Technology Directorate; National Institutes of Health National Institute
for Allergy and Infectious Diseases [K08AI067549]; US Department of
Homeland Security; US Agency:for International Development [1272]
FX This work was supported by a National Institutes of Health/National
Science Foundation "Ecology and Evolution of Infectious Diseases" award
from the Fogarty International Center (Grant 2R01-TW005869), National
Institute of Allergy and Infectious Diseases Grant 1 R01 AI079231, a
National Science Foundation Human and Social Dynamics Agents of Change
award (BCS 0826779 and BCS 0826840), the Research and Policy for
Infectious Disease Dynamics program of the Science and Technology
Directorate, the National Institutes of Health National Institute for
Allergy and Infectious Diseases (Grant K08AI067549), and the US
Department of Homeland Security, as well as by the generous support of
the American people through the US Agency:for International Development
(Grant 1272) "Emerging Pandemic Threats" (PREDICT).
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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 FEB 26
PY 2013
VL 110
SU 1
BP 3681
EP 3688
DI 10.1073/pnas.1201243109
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 102JY
UT WOS:000315842100005
PM 22936052
ER
PT J
AU Harrington, WE
Morrison, R
Fried, M
Duffy, PE
AF Harrington, Whitney E.
Morrison, Robert
Fried, Michal
Duffy, Patrick E.
TI Intermittent Preventive Treatment in Pregnant Women Is Associated with
Increased Risk of Severe Malaria in Their Offspring
SO PLOS ONE
LA English
DT Article
ID PLASMODIUM-FALCIPARUM MALARIA; PLACENTAL MALARIA; FACILITATION;
INFECTIONS; RESISTANCE; MORBIDITY; PARASITES; EFFICACY; IMMUNITY; MODEL
AB Background: In areas of widespread sulfadoxine-pyrimethamine resistance, intermittent treatment in pregnancy (IPTp) fails to prevent placental malaria (PM) and may exacerbate drug resistant infections. Because PM predicts increased susceptibility to parasitemia during infancy, we hypothesized that IPTp would also increase susceptibility to malaria infection and disease in the offspring.
Methods: In a birth cohort from NE Tanzania, we evaluated the association between maternal IPTp use and risk of parasitemia and severe malaria in the offspring. Using Cox Proportional Hazards Models as well as Generalized Estimating Equations, we evaluated the effects of IPTp on the entire cohort and on subgroups stratified by PM status at delivery.
Results and Conclusions: Offspring of PM+ women who received IPTp had a dose-dependent decrease in time to first parasitemia (AHR = 2.13, p = 0.04 [95%CI: 1.04, 4.38]). Among all offspring, IPTp was associated with earlier first severe malaria episode (AHR = 2.32, p = 0.02 [95%CI: 1.12, 4.78]) as well as increased overall odds of severe malaria (AOR = 2.31, p = 0.03 [95%CI: 1.09, 4.88]). Cost-benefit analyses of IPTp regimens should consider the long term effects on offspring in addition to pregnancy outcomes.
C1 [Harrington, Whitney E.] Univ Washington, Sch Med, Dept Pediat, Seattle Childrens Hosp, Seattle, WA 98195 USA.
[Morrison, Robert] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Fried, Michal; Duffy, Patrick E.] NIAID, NIH, Rockville, MD USA.
RP Duffy, PE (reprint author), NIAID, NIH, Rockville, MD USA.
EM patrick.duffy@nih.gov
FU Bill & Melinda Gates Foundation [29202]; Foundation for the National
Institutes of Health through the Grand Challenges in Global Health
Initiative [1364]; U.S. National Institutes of Health Fogarty
International Center (FIC) [D43 TW005509]; National Institute of Allergy
and Infectious Diseases [R01AI52059]; National Heart, Lung, and Blood
Institute (NIH Fellowship) [1F30HL096298]
FX Funding was provided by the Bill & Melinda Gates Foundation (Grant
29202), the Foundation for the National Institutes of Health through the
Grand Challenges in Global Health Initiative (Grant 1364), the U.S.
National Institutes of Health Fogarty International Center (FIC) (Grant
D43 TW005509), and the National Institute of Allergy and Infectious
Diseases (R01AI52059) to PED, and by the National Heart, Lung, and Blood
Institute (NIH Fellowship 1F30HL096298) to WEH. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript. The content is solely the responsibility
of the authors and does not represent the official views of the funding
sources.
NR 25
TC 14
Z9 14
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 FEB 25
PY 2013
VL 8
IS 2
AR e56183
DI 10.1371/journal.pone.0056183
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 115ZB
UT WOS:000316849500008
PM 23451036
ER
PT J
AU Kumar, NP
Sridhar, R
Banurekha, VV
Nair, D
Jawahar, MS
Nutman, TB
Babu, S
AF Kumar, Nathella Pavan
Sridhar, Rathinam
Banurekha, Vaithilingam V.
Nair, Dina
Jawahar, Mohideen S.
Nutman, Thomas B.
Babu, Subash
TI Expansion of Pathogen-Specific Mono- and Multifunctional Th1 and Th17
Cells in Multi-Focal Tuberculous Lymphadenitis
SO PLOS ONE
LA English
DT Article
ID REGULATORY T-CELLS; ACTIVE PULMONARY TUBERCULOSIS;
MYCOBACTERIUM-TUBERCULOSIS; IFN-GAMMA; IMMUNE-RESPONSE;
INTERFERON-GAMMA; INFECTION; DISEASE; MICE; EXPRESSION
AB Background: Th1 and Th17 responses are known to play an important role in immunity to pulmonary tuberculosis (PTB), although little is known about their role in extrapulmonary forms of tuberculosis (TB).
Methods: To identify the role of Th1, Th17, and Th22 cells in multi-focal TB lymphadenitis (TBL), we examined mycobacteria-specific immune responses in the whole blood of individuals with PTB (n = 20) and compared them with those with TBL (n = 25).
Results: Elevated frequencies of CD4(+) T cells expressing IFN- gamma, TNF-alpha, and IL-2 were present in individuals with TBL compared with those with PTB at baseline and in response to ESAT-6 and CFP-10. Similarly, increased frequencies of CD4(+) T cells expressing IL-17A, IL-17F, and IFN-gamma were also present in individuals with TBL at baseline and following ESAT-6 and CFP-10 stimulation although no significant difference in frequency of Th22 cells was observed. Finally, frequencies of Th1 (but not Th17) cells exhibited a significantly negative correlation with natural regulatory T cell frequencies at baseline.
Conclusions: Multi-focal TB lymphadenitis is therefore characterized by elevated frequencies of Th1 and Th17 cells, indicating that Th1 and Th17 responses in TB disease are probably correlates of disease severity rather than of protective immunity.
C1 [Kumar, Nathella Pavan; Babu, Subash] Int Ctr Excellence Res, Natl Inst Hlth, Chennai, Tamil Nadu, India.
[Sridhar, Rathinam] Govt Stanley Med Hosp, Chennai, Tamil Nadu, India.
[Banurekha, Vaithilingam V.; Nair, Dina; Jawahar, Mohideen S.] Natl Inst Res TB, Chennai, Tamil Nadu, India.
[Nutman, Thomas B.; Babu, Subash] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Babu, S (reprint author), Int Ctr Excellence Res, Natl Inst Hlth, Chennai, Tamil Nadu, India.
EM sbabu@mail.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH)
FX This work was supported in part by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH). No additional external funding was received
for this study. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 43
TC 2
Z9 2
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 25
PY 2013
VL 8
IS 2
AR e57123
DI 10.1371/journal.pone.0057123
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 115ZB
UT WOS:000316849500066
PM 23451159
ER
PT J
AU Lin, FR
Yaffe, K
Xia, J
Xue, QL
Harris, TB
Purchase-Helzner, E
Satterfield, S
Ayonayon, HN
Ferrucci, L
Simonsick, EM
AF Lin, Frank R.
Yaffe, Kristine
Xia, Jin
Xue, Qian-Li
Harris, Tamara B.
Purchase-Helzner, Elizabeth
Satterfield, Suzanne
Ayonayon, Hilsa N.
Ferrucci, Luigi
Simonsick, Eleanor M.
CA Hlth ABC Study Grp
TI Hearing Loss and Cognitive Decline in Older Adults
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID OF-THE-SCIENCE; ALZHEIMERS-DISEASE; BODY-COMPOSITION; UNITED-STATES;
RISK-FACTORS; HEALTH ABC; IMPAIRMENT; DEMENTIA; POPULATION; AGE
AB Background: Whether hearing loss is independently associated with accelerated cognitive decline in older adults is unknown.
Methods: We studied 1984 older adults (mean age, 77.4 years) enrolled in the Health ABC Study, a prospective observational study begun in 1997-1998. Our baseline cohort consisted of participants without prevalent cognitive impairment (Modified Mini-Mental State Examination [3MS] score, >= 80) who underwent audiometric testing in year 5. Participants were followed up for 6 years. Hearing was defined at baseline using a pure-tone average of thresholds at 0.5 to 4 kHz in the better-hearing ear. Cognitive testing was performed in years 5, 8, 10, and 11 and consisted of the 3MS (measuring global function) and the Digit Symbol Substitution test (measuring executive function). Incident cognitive impairment was defined as a 3MS score of less than 80 or a decline in 3MS score of more than 5 points from baseline. Mixed-effects regression and Cox proportional hazards regression models were adjusted for demographic and cardiovascular risk factors.
Results: In total, 1162 individuals with baseline hearing loss (pure-tone average >25 dB) had annual rates of decline in 3MS and Digit Symbol Substitution test scores that were 41% and 32% greater, respectively, than those among individuals with normal hearing. On the 3MS, the annual score changes were -0.65 (95% CI, -0.73 to -0.56) vs -0.46 (95% CI, -0.55 to -0.36) points per year (P=.004). On the Digit Symbol Substitution test, the annual score changes were -0.83 (95% CI, -0.94 to -0.73) vs -0.63 (95% CI, -0.75 to -0.51) points per year (P=.02). Compared to those with normal hearing, individuals with hearing loss at baseline had a 24% (hazard ratio, 1.24; 95% CI, 1.05-1.48) increased risk for incident cognitive impairment. Rates of cognitive decline and the risk for incident cognitive impairment were linearly associated with the severity of an individual's baseline hearing loss.
Conclusions: Hearing loss is independently associated with accelerated cognitive decline and incident cognitive impairment in community-dwelling older adults. Further studies are needed to investigate what the mechanistic basis of this association is and whether hearing rehabilitative interventions could affect cognitive decline.
C1 [Lin, Frank R.] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA.
[Lin, Frank R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Lin, Frank R.; Xia, Jin; Xue, Qian-Li] Johns Hopkins Ctr Aging & Hlth, Baltimore, MD USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Ferrucci, Luigi; Simonsick, Eleanor M.] NIA, Intramural Res Program, Bethesda, MD 20892 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat & Neurol, San Francisco, CA 94143 USA.
[Yaffe, Kristine; Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Purchase-Helzner, Elizabeth] Suny Downstate Med Ctr, Dept Epidemiol & Biostat, Brooklyn, NY 11203 USA.
[Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA.
RP Lin, FR (reprint author), Johns Hopkins Ctr Aging & Hlth, 2024 E Monument St,Ste 2-700, Baltimore, MD 21205 USA.
EM flin1@jhmi.edu
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
FU National Institute on Aging [R01-AG028050]; Johns Hopkins Older
Americans Independence Center from the National Institute on Aging
[P30-AG02133]; National Institute of Nursing Research [R01-NR012459];
National Institute on Deafness and Other Communication Disorders
[K23DC011279]; Triological Society/American College of Surgeons
Clinician Scientist Award; [N01-AG62101]; [N01-AG62103];
[N01-AG62106]
FX This study was funded by contracts N01-AG62101, N01-AG62103, and
N01-AG62106 and grant R01-AG028050 from the National Institute on Aging
and The Johns Hopkins Older Americans Independence Center under contract
P30-AG02133 from the National Institute on Aging (Dr Xue) and by grants
R01-NR012459 from the National Institute of Nursing Research and
K23DC011279 from the National Institute on Deafness and Other
Communication Disorders and by a Triological Society/American College of
Surgeons Clinician Scientist Award (Dr Lin).
NR 50
TC 184
Z9 196
U1 7
U2 63
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 FEB 25
PY 2013
VL 173
IS 4
BP 293
EP 299
DI 10.1001/jamainternmed.2013.1868
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 153NZ
UT WOS:000319610400009
PM 23337978
ER
PT J
AU Selvaraj, S
Prasad, V
AF Selvaraj, Senthil
Prasad, Vinay
TI Characteristics of Cluster Randomized Trials: Are They Living Up to the
Randomized Trial?
SO JAMA INTERNAL MEDICINE
LA English
DT Letter
C1 [Selvaraj, Senthil] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 12N226, Bethesda, MD 20892 USA.
EM vinayak.prasad@nih.gov
NR 5
TC 1
Z9 1
U1 0
U2 2
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 FEB 25
PY 2013
VL 173
IS 4
BP 313
EP 315
DI 10.1001/jamainternmed.2013.1638
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 153NZ
UT WOS:000319610400015
PM 23337957
ER
PT J
AU Hakkinen, PJ
AF Hakkinen, Pertti J.
TI New Studies About Everyday Types of Chemical Exposures: What Readers
Should Consider
SO JAMA INTERNAL MEDICINE
LA English
DT Editorial Material
ID MELAMINE; FORMALDEHYDE; MIGRATION
C1 NIH, Off Clin Toxicol, Specialized Informat Serv, Natl Lib Med, Bethesda, MD 20892 USA.
RP Hakkinen, PJ (reprint author), NIH, Off Clin Toxicol, Specialized Informat Serv, Natl Lib Med, 6707 Democracy Blvd,Ste 510, Bethesda, MD 20892 USA.
EM pertti.hakkinen@nih.gov
RI Hakkinen, Pertti/G-4803-2016
OI Hakkinen, Pertti/0000-0002-8295-9738
NR 9
TC 1
Z9 1
U1 0
U2 2
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 FEB 25
PY 2013
VL 173
IS 4
BP 319
EP 320
DI 10.1001/jamainternmed.2013.2133
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 153NZ
UT WOS:000319610400019
PM 23338122
ER
PT J
AU Vinuelas, J
Kaneko, G
Coulon, A
Vallin, E
Morin, V
Mejia-Pous, C
Kupiec, JJ
Beslon, G
Gandrillon, O
AF Vinuelas, Jose
Kaneko, Gael
Coulon, Antoine
Vallin, Elodie
Morin, Valerie
Mejia-Pous, Camila
Kupiec, Jean-Jacques
Beslon, Guillaume
Gandrillon, Olivier
TI Quantifying the contribution of chromatin dynamics to stochastic gene
expression reveals long, locus-dependent periods between transcriptional
bursts
SO BMC BIOLOGY
LA English
DT Article
DE Chromatin dynamics; expression noise; gene regulation; stochastic model
ID SINGLE-CELL; HISTONE DEACETYLATION; ESCHERICHIA-COLI; DNA METHYLATION;
TRICHOSTATIN-A; HUMAN GENOME; NOISE; PROMOTER; DIFFERENTIATION;
FLUCTUATIONS
AB Background: A number of studies have established that stochasticity in gene expression may play an important role in many biological phenomena. This therefore calls for further investigations to identify the molecular mechanisms at stake, in order to understand and manipulate cell-to-cell variability. In this work, we explored the role played by chromatin dynamics in the regulation of stochastic gene expression in higher eukaryotic cells.
Results: For this purpose, we generated isogenic chicken-cell populations expressing a fluorescent reporter integrated in one copy per clone. Although the clones differed only in the genetic locus at which the reporter was inserted, they showed markedly different fluorescence distributions, revealing different levels of stochastic gene expression. Use of chromatin-modifying agents showed that direct manipulation of chromatin dynamics had a marked effect on the extent of stochastic gene expression. To better understand the molecular mechanism involved in these phenomena, we fitted these data to a two-state model describing the opening/closing process of the chromatin. We found that the differences between clones seemed to be due mainly to the duration of the closed state, and that the agents we used mainly seem to act on the opening probability.
Conclusions: In this study, we report biological experiments combined with computational modeling, highlighting the importance of chromatin dynamics in stochastic gene expression. This work sheds a new light on the mechanisms of gene expression in higher eukaryotic cells, and argues in favor of relatively slow dynamics with long (hours to days) periods of quiet state.
C1 [Vinuelas, Jose; Kaneko, Gael; Vallin, Elodie; Morin, Valerie; Mejia-Pous, Camila; Gandrillon, Olivier] Univ Lyon 1, Univ Lyon, Ctr Genet & Physiol Mol & Cellulaire CGPhiMC, CNRS UMR5534, F-69622 Lyon, France.
[Kaneko, Gael; Beslon, Guillaume] Univ Lyon, Lab InfoRmat Image & Systemes Informat LIRIS, INSA Lyon, INRIA,CNRS UMR5205, F-69621 Lyon, France.
[Coulon, Antoine] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Kupiec, Jean-Jacques] Ecole Normale Super, Ctr Cavailles, INSERM, F-75005 Paris, France.
RP Gandrillon, O (reprint author), Univ Lyon 1, Univ Lyon, Ctr Genet & Physiol Mol & Cellulaire CGPhiMC, CNRS UMR5534, F-69622 Lyon, France.
EM olivier.gandrillon@univ-lyon1.fr
RI Beslon, Guillaume/D-7369-2014; Coulon, Antoine/A-9006-2012
FU Institut Rhonalpin des Systemes Complexes (IXXI); Reseau National des
Systemes Complexes (RNSC); ANR grant [ANR 2011 BSV6 014 01]; CNRS
post-doctoral grant
FX We thank Francois Chatelain, Alexandra Fuchs, and Manuel Thery for
helpful discussions and support during the early stages of the project.
We are grateful to Denis Ressnikoff of the platform Centre Commun de
Quantimetrie de Lyon (CCQ) for flow-cytometry cell-sorting assistance.
We thank the Centre de Calcul de l'Institut National de Physique
Nucleaire et de Physique des Particules de Lyon (CC-IN2P3), and
especially Pascal Calvat, for their computing resources. We also thank
the interns who worked on this project: Mathieu Gineste, Yoann Meniere,
Charles Rocabert. and Balthazar Rouberol. We thank the Andras Paldi
group from the Genethon for the constructive and useful discussions on
chromatin and stochasticity of gene expression. This work was supported
by funding from the Institut Rhonalpin des Systemes Complexes (IXXI) and
from the Reseau National des Systemes Complexes (RNSC). Part of the
project was supported by an ANR grant (ANR 2011 BSV6 014 01). JV is
supported by a CNRS post-doctoral grant and GK is a PhD Fellow from the
Region Rhone Alpes and INRIA.
NR 86
TC 22
Z9 22
U1 0
U2 19
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7007
J9 BMC BIOL
JI BMC Biol.
PD FEB 25
PY 2013
VL 11
AR 15
DI 10.1186/1741-7007-11-15
PG 19
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 138EE
UT WOS:000318490700001
PM 23442824
ER
PT J
AU Vivar, C
van Praag, H
AF Vivar, Carmen
van Praag, Henriette
TI Functional circuits of new neurons in the dentate gyrus
SO FRONTIERS IN NEURAL CIRCUITS
LA English
DT Review
DE dentate gyrus; adult neurogenesis; rabies virus; retrograde
trans-neuronal tracing; learning and memory; area CA3; lateral
entorhinal cortex; pattern separation
ID ADULT HIPPOCAMPAL NEUROGENESIS; GENERATED GRANULE CELLS; NEURAL
STEM-CELLS; ENHANCED SYNAPTIC PLASTICITY; SPATIAL-PATTERN SEPARATION;
SOURCE DENSITY ANALYSIS; CENTRAL-NERVOUS-SYSTEM; MEDIAL TEMPORAL-LOBE;
RABIES VIRUS; IN-VIVO
AB The hippocampus is crucial for memory formation. New neurons are added throughout life to the hippocampal dentate gyrus (DG), a brain area considered important for differential storage of similar experiences and contexts. To better understand the functional contribution of adult neurogenesis to pattern separation processes, we recently used a novel synapse specific trans-neuronal tracing approach to identify the (sub) cortical inputs to new dentate granule cells (GCs). It was observed that newly born neurons receive sequential innervation from structures important for memory function. Initially, septal-hippocampal cells provide input to new neurons, including transient innervation from mature GCs as well as direct feedback from area CA3 pyramidal neurons. After about 1 month perirhinal (PRH) and lateral entorhinal cortex (LEC), brain areas deemed relevant to integration of novel sensory and environmental information, become substantial input to new GCs. Here, we review the developmental time-course and proposed functional relevance of new neurons, within the context of their unique neural circuitry.
C1 [Vivar, Carmen; van Praag, Henriette] NIA, Neuroplast & Behav Unit, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP van Praag, H (reprint author), NIA, Neuroplast & Behav Unit, Neurosci Lab, Biomed Res Ctr,NIH, Suite 100,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM vanpraagh@mail.nih.gov
RI van Praag, Henriette/F-3939-2015
OI van Praag, Henriette/0000-0002-5727-434X
FU National Institute on Aging, Intramural Research Program
FX This work was supported by the National Institute on Aging, Intramural
Research Program. We thank Linda R. Kitabayashi for help with
preparation of the photomicrographs.
NR 193
TC 45
Z9 47
U1 1
U2 38
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5110
J9 FRONT NEURAL CIRCUIT
JI Front. Neural Circuits
PD FEB 25
PY 2013
VL 7
AR 15
DI 10.3389/fncir.2013.00015
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 125SC
UT WOS:000317560600001
PM 23443839
ER
PT J
AU Yaniv, Y
Spurgeon, HA
Ziman, BD
Lakatta, EG
AF Yaniv, Yael
Spurgeon, Harold A.
Ziman, Bruce D.
Lakatta, Edward G.
TI Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII) Activity and
Sinoatrial Nodal Pacemaker Cell Energetics
SO PLOS ONE
LA English
DT Article
ID CA2+ RELEASES; K+ CHANNELS; CALMODULIN; HEART; CALCIUM; CONTRACTION;
MYOCYTES; PHOSPHORYLATION; AUTOMATICITY; ACTIVATION
AB Ca2+-activated basal adenylate cyclase (AC) in rabbit sinoatrial node cells (SANC) guarantees, via basal cAMP/PKA-calmodulin/CaMKII-dependent protein phosphorylation, the occurrence of rhythmic, sarcoplasmic-reticulum generated, sub-membrane Ca2+ releases that prompt rhythmic, spontaneous action potentials (APs). This high-throughput signaling consumes ATP.
Aims: We have previously demonstrated that basal AC-cAMP/PKA signaling directly, and Ca2+ indirectly, regulate mitochondrial ATP production. While, clearly, Ca2+-calmodulin-CaMKII activity regulates ATP consumption, whether it has a role in the control of ATP production is unknown.
Methods and Results: We superfused single, isolated rabbit SANC at 37 degrees C with physiological saline containing CaMKII inhibitors, (KN-93 or autocamtide-2 Related Inhibitory Peptide (AIP)), or a calmodulin inhibitor (W-7) and measured cytosolic Ca2+, flavoprotein fluorescence and spontaneous AP firing rate. We measured cAMP, ATP and O-2 consumption in cell suspensions. Graded reductions in basal CaMKII activity by KN-93 (0.5-3 mu mol/L) or AIP (2-10 mu mol/L) markedly slow the kinetics of intracellular Ca2+ cycling, decrease the spontaneous AP firing rate, decrease cAMP, and reduce O-2 consumption and flavoprotein fluorescence. In this context of graded reductions in ATP demand, however, ATP also becomes depleted, indicating reduced ATP production.
Conclusions: CaMKII signaling, a crucial element of normal automaticity in rabbit SANC, is also involved in SANC bioenergetics.
C1 [Yaniv, Yael; Spurgeon, Harold A.; Ziman, Bruce D.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
EM LakattaE@mail.nih.gov
RI Yaniv, Yael/B-3311-2015
OI Yaniv, Yael/0000-0002-5183-6284
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health
FX The work was supported entirely by the Intramural Research Program of
the 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.
NR 32
TC 14
Z9 14
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 FEB 25
PY 2013
VL 8
IS 2
AR e57079
DI 10.1371/journal.pone.0057079
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 115ZB
UT WOS:000316849500062
PM 23459256
ER
PT J
AU Li, Y
Lee, C
Lam, KH
Shung, KK
AF Li, Ying
Lee, Changyang
Lam, Kwok Ho
Shung, K. Kirk
TI A simple method for evaluating the trapping performance of acoustic
tweezers
SO APPLIED PHYSICS LETTERS
LA English
DT Article
ID ULTRASONIC TRANSDUCERS; RADIATION PRESSURE; DIELECTRIC SPHERE; FORCES;
FEASIBILITY; CALIBRATION; REGIME; TRAPS
AB The purpose of this paper is to present a rapid and simple method to evaluate the trapping performance of high frequency focused ultrasonic transducers for acoustic tweezer applications. The method takes into consideration the friction between the particle to be trapped and the surface that it resides on. As a result it should be more reliable and accurate than the methods proposed previously. The trapping force produced by a 70-MHz press-focused transducer was measured to evaluate the performance of this approach. This method demonstrates its potential in optimizing the excitation conditions for acoustic tweezer applications and the design of acoustic tweezers. (C) 2013 American Institute of Physics. [http://dx.doi.org/10.1063/1.4793654]
C1 [Li, Ying] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA.
Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
RP Li, Y (reprint author), Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA.
EM yli582@usc.edu
RI Lam, K.H./B-7765-2014;
OI Lam, K.H./0000-0003-1456-9049; Lee, Changyang/0000-0002-3746-7304
FU NIH [R01-EB12058, P41-EB02182]
FX The authors would like to thank Dr. Qifa Zhou, Dr. Hyung Ham Kim and Dr.
Jae Youn Hwang for their help in this work. This work has been supported
by NIH Grant Nos. R01-EB12058 and P41-EB02182.
NR 17
TC 6
Z9 6
U1 0
U2 27
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0003-6951
J9 APPL PHYS LETT
JI Appl. Phys. Lett.
PD FEB 25
PY 2013
VL 102
IS 8
AR 084102
DI 10.1063/1.4793654
PG 4
WC Physics, Applied
SC Physics
GA 099CN
UT WOS:000315597000089
PM 23526834
ER
PT J
AU Prinz, WA
AF Prinz, William A.
TI A Bridge to Understanding Lipid Droplet Growth
SO DEVELOPMENTAL CELL
LA English
DT Editorial Material
AB Lipid droplets, storage sites of fatty acids and sterols, expand when excess lipids are converted to triacylglycerols. In this issue of Developmental Cell, Wilfling et al. (2013) show that this expansion relies on relocalization, via membrane bridges, of triacylglycerol-synthesizing enzymes from the ER to a subset of lipid droplets'.
C1 NIDDKD, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Prinz, WA (reprint author), NIDDKD, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM prinzw@helix.nih.gov
FU Intramural NIH HHS [ZIA DK060004-11]
NR 4
TC 4
Z9 4
U1 0
U2 21
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD FEB 25
PY 2013
VL 24
IS 4
BP 335
EP 336
DI 10.1016/j.devcel.2013.02.004
PG 2
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 097KK
UT WOS:000315472800001
PM 23449466
ER
PT J
AU Li, WL
Kohara, H
Uchida, Y
James, JM
Soneji, K
Cronshaw, DG
Zou, YR
Nagasawa, T
Mukouyama, YS
AF Li, Wenling
Kohara, Hiroshi
Uchida, Yutaka
James, Jennifer M.
Soneji, Kosha
Cronshaw, Darran G.
Zou, Yong-Rui
Nagasawa, Takashi
Mukouyama, Yoh-suke
TI Peripheral Nerve-Derived CXCL12 and VEGF-A Regulate the Patterning of
Arterial Vessel Branching in Developing Limb Skin
SO DEVELOPMENTAL CELL
LA English
DT Article
ID ENDOTHELIAL-GROWTH-FACTOR; BONE-MARROW; IN-VIVO; RECEPTOR; MICE;
DIFFERENTIATION; ANGIOGENESIS; DEFECTS; VASCULATURE; MECHANISMS
AB In developing limb skin, peripheral nerves provide a spatial template that controls the branching pattern and differentiation of arteries. Our previous studies indicate that nerve-derived VEGF-A is required for arterial differentiation but not for nerve-vessel alignment. In this study, we demonstrate that nerve-vessel alignment depends on the activity of Cxcl12-Cxcr4 chemokine signaling. Genetic inactivation of Cxcl12-Cxcr4 signaling perturbs nerve-vessel alignment and abolishes arteriogenesis. Further in vitro assays allow us to uncouple nerve-vessel alignment and arteriogenesis, revealing that nerve-derived Cxcl12 stimulates endothelial cell migration, whereas nerve-derived VEGF-A is responsible for arterial differentiation. These findings suggest a coordinated sequential action in which nerve Cxcl12 functions over a distance to recruit vessels to align with nerves, and subsequent arterial differentiation presumably requires a local action of nerve VEGF-A in the nerve-associated vessels.
C1 [Li, Wenling; Uchida, Yutaka; James, Jennifer M.; Soneji, Kosha; Mukouyama, Yoh-suke] NHLBI, Lab Stem Cell & Neurovasc Biol, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Kohara, Hiroshi; Nagasawa, Takashi] Kyoto Univ, Inst Frontier Med Sci, Dept Immunobiol & Hematol, Sakyo Ku, Shogoin, Kyoto 6068507, Japan.
[Cronshaw, Darran G.; Zou, Yong-Rui] Feinstein Inst Med Res, Ctr Autoimmune & Musculoskeletal Dis, Manhasset, NY 11030 USA.
RP Mukouyama, YS (reprint author), NHLBI, Lab Stem Cell & Neurovasc Biol, Genet & Dev Biol Ctr, NIH, Bldg 10-6C103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mukoyamay@mail.nih.gov
FU National Heart, Lung, and Blood Institute, National Institutes of Health
FX We thank X. Chi and F. Costantini for breeding Cxcr7 mutants, A.L.
Kolodkin for providing anti-Nrp1 antibody, T. Muller for providing
anti-BFABP antibody, M. Taniguchi for providing Sema3A mutants, and N.
Takakura for providing anti-ephrinB2 antibody. Thanks to L Samsel, P.
Dagur, H. Sardon, and J.P. McCoy for FACS assistance, J. Hawkins and the
staff of the National Institutes of Health Building 50 animal facility
for assistance with mouse breeding and care, K. Gill for laboratory
management and technical support, and Y. Carter and L. Oundo for
administrative assistance. Thanks also to A.M. Michelson, R.S. Balaban,
R.S. Adelstein, J.S. Gutkind, and H. Yagi for invaluable help and
discussion, H. Zang and M.A. Conti for editorial advice on the
manuscript, and other members of the Laboratory of Stem Cell and
Neuro-Vascular Biology for technical help and thoughtful discussion.
This work was supported by the Intramural Research Program of the
National Heart, Lung, and Blood Institute, National Institutes of
Health.
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U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
EI 1878-1551
J9 DEV CELL
JI Dev. Cell
PD FEB 25
PY 2013
VL 24
IS 4
BP 359
EP 371
DI 10.1016/j.devcel.2013.01.009
PG 13
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 097KK
UT WOS:000315472800007
PM 23395391
ER
PT J
AU Hasenour, CM
Berglund, ED
Wasserman, DH
AF Hasenour, Clinton M.
Berglund, Eric D.
Wasserman, David H.
TI Emerging role of AMP-activated protein kinase in endocrine control of
metabolism in the liver
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Review
DE AMPK; Endocrine; Glucagon; Adiponectin; Energy charge; Metabolism
ID ACETYL-COA CARBOXYLASE; PERFUSED-RAT-LIVER; FATTY-ACID OXIDATION;
INHIBITS HEPATIC GLUCONEOGENESIS; CREB COACTIVATOR TORC2;
GLUCOSE-PRODUCTION; SKELETAL-MUSCLE; LIPID-METABOLISM; GENE-EXPRESSION;
ENERGY-STATE
AB This review summarizes the emerging role of AMP-activated protein kinase (AMPK) in mediating endocrine regulation of metabolic fluxes in the liver. There are a number of hormones which, when acting on the liver, alter AMPK activation. Here we describe those hormones associated with activation and de-activation of AMPK and the potential mechanisms for changes in AMPK activation state. The actions of these hormones, in many cases, are consistent with downstream effects of AMPK signaling thus strengthening the circumstantial case for AMPK-mediated hormone action. In recent years, genetic mouse models have also been used in an attempt to establish the role of AMPK in hormone-stimulated metabolism in the liver. Few experiments have, however, firmly established a causal relationship between hormone action at the liver and AMPK signaling. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA.
RP Hasenour, CM (reprint author), Vanderbilt Univ, Sch Med, Light Hall,Room 702, Nashville, TN 37232 USA.
EM clinton.m.hasenour@vanderbilt.edu
FU NIH [R37 DK050277, U24 DK059637]
FX This work was supported by Grants, NIH R37 DK050277 and U24 DK059637.
NR 129
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U1 1
U2 22
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 FEB 25
PY 2013
VL 366
IS 2
SI SI
BP 152
EP 162
DI 10.1016/j.mce.2012.06.018
PG 11
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 095AD
UT WOS:000315306000004
PM 22796337
ER
PT J
AU Caughlin, TT
Ruktanonchai, N
Acevedo, MA
Lopiano, KK
Prosper, O
Eagle, N
Tatem, AJ
AF Caughlin, T. Trevor
Ruktanonchai, Nick
Acevedo, Miguel A.
Lopiano, Kenneth K.
Prosper, Olivia
Eagle, Nathan
Tatem, Andrew J.
TI Place-Based Attributes Predict Community Membership in a Mobile Phone
Communication Network
SO PLOS ONE
LA English
DT Article
ID SOCIAL NETWORK; MODULARITY; SPREAD
AB Social networks can be organized into communities of closely connected nodes, a property known as modularity. Because diseases, information, and behaviors spread faster within communities than between communities, understanding modularity has broad implications for public policy, epidemiology and the social sciences. Explanations for community formation in social networks often incorporate the attributes of individual people, such as gender, ethnicity or shared activities. High modularity is also a property of large-scale social networks, where each node represents a population of individuals at a location, such as call flow between mobile phone towers. However, whether or not place-based attributes, including land cover and economic activity, can predict community membership for network nodes in large-scale networks remains unknown. We describe the pattern of modularity in a mobile phone communication network in the Dominican Republic, and use a linear discriminant analysis (LDA) to determine whether geographic context can explain community membership. Our results demonstrate that place-based attributes, including sugar cane production, urbanization, distance to the nearest airport, and wealth, correctly predicted community membership for over 70% of mobile phone towers. We observed a strongly positive correlation (r = 0.97) between the modularity score and the predictive ability of the LDA, suggesting that place-based attributes can accurately represent the processes driving modularity. In the absence of social network data, the methods we present can be used to predict community membership over large scales using solely place-based attributes.
C1 [Caughlin, T. Trevor; Ruktanonchai, Nick] Univ Florida, Dept Biol, Gainesville, FL 32611 USA.
[Acevedo, Miguel A.] Univ Florida, Sch Nat Resources & Conservat, Dept Wildlife Ecol & Conservat, Gainesville, FL USA.
[Lopiano, Kenneth K.] Univ Florida, Dept Stat, Gainesville, FL 32611 USA.
[Prosper, Olivia] Univ Florida, Dept Math, Gainesville, FL 32611 USA.
[Eagle, Nathan] MIT, Media Lab, Cambridge, MA 02139 USA.
[Eagle, Nathan] Santa Fe Inst, Santa Fe, NM 87501 USA.
[Tatem, Andrew J.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Tatem, Andrew J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA.
[Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Caughlin, TT (reprint author), Univ Florida, Dept Biol, Gainesville, FL 32611 USA.
EM trevor.caughlin@gmail.com
FU National Science Foundation at the University of Florida [0801544]; Bill
and Melinda Gates Foundation [49446, OPP1032350]; RAPIDD program of the
Science & Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health
FX TTC, NR, MAA, KL, and OP were supported by the National Science
Foundation (http://www.nsf.gov/) under grant 0801544 at the University
of Florida. AJT is supported by grants from the Bill and Melinda Gates
Foundation (www.gatesfoundation.org/) under grants 49446 and
OPP1032350). AJT also acknowledges funding support from the RAPIDD
program of the Science & Technology Directorate, Department of Homeland
Security (www.dhs.gov), and the Fogarty International Center, National
Institutes of Health (http://www.fic.nih.gov). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 31
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U1 1
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 FEB 22
PY 2013
VL 8
IS 2
AR e56057
DI 10.1371/journal.pone.0056057
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113IC
UT WOS:000316658800006
PM 23451034
ER
PT J
AU Meyer, J
Gorbach, AM
Liu, WM
Medic, N
Young, M
Nelson, C
Arceo, S
Desai, A
Metcalfe, DD
Komarow, HD
AF Meyer, Joseph
Gorbach, Alexander M.
Liu, Wei-Min
Medic, Nevenka
Young, Michael
Nelson, Celeste
Arceo, Sarah
Desai, Avanti
Metcalfe, Dean D.
Komarow, Hirsh D.
TI Mast Cell Dependent Vascular Changes Associated with an Acute Response
to Cold Immersion in Primary Contact Urticaria
SO PLOS ONE
LA English
DT Article
ID ALLERGIC INFLAMMATION; CHOLINERGIC URTICARIA; HISTAMINE; ANAPHYLAXIS;
BASOPHILS; TRYPTASE; RELEASE; MICROCIRCULATION; PATHOPHYSIOLOGY;
DEGRANULATION
AB Background: While a number of the consequences of mast cell degranulation within tissues have been documented including tissue-specific changes such as bronchospasm and the subsequent cellular infiltrate, there is little known about the immediate effects of mast cell degranulation on the associated vasculature, critical to understanding the evolution of mast cell dependent inflammation.
Objective: To characterize the microcirculatory events that follow mast cell degranulation.
Methodology/Principal Findings: Perturbations in dermal blood flow, temperature and skin color were analyzed using laser-speckle contrast imaging, infrared and polarized-light colorimetry following cold-hand immersion (CHI) challenge in patients with cold-induced urticaria compared to the response in healthy controls. Evidence for mast cell degranulation was established by documentation of serum histamine levels and the localized release of tryptase in post-challenge urticarial biopsies. Laser-speckle contrast imaging quantified the attenuated response to cold challenge in patients on cetirizine. We found that the histamine-associated vascular response accompanying mast cell degranulation is rapid and extensive. At the tissue level, it is characterized by a uniform pattern of increased blood flow, thermal warming, vasodilation, and recruitment of collateral circulation. These vascular responses are modified by the administration of an antihistamine.
Conclusions/Significance: Monitoring the hemodynamic responses within tissues that are associated with mast cell degranulation provides additional insight into the evolution of the acute inflammatory response and offers a unique approach to assess the effectiveness of treatment intervention.
C1 [Meyer, Joseph; Gorbach, Alexander M.; Liu, Wei-Min] Natl Inst Biomed Imaging & Bioengn, Infrared Imaging & Thermometry Unit, NIH, Bethesda, MD USA.
[Medic, Nevenka; Nelson, Celeste; Arceo, Sarah; Desai, Avanti; Metcalfe, Dean D.; Komarow, Hirsh D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Young, Michael] NCI, Clin Res Directorate, CMRP, SAIC Frederick, Frederick, MD 21701 USA.
RP Komarow, HD (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM komarowh@niaid.nih.gov
FU Division of Intramural Research, NIAID, NIH; National Cancer Institute,
National Institutes of Health [HHSN261200800001E]
FX This work was supported by the Division of Intramural Research, NIAID,
NIH. Support by M.Y. for 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. The funders 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 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 FEB 22
PY 2013
VL 8
IS 2
AR e56773
DI 10.1371/journal.pone.0056773
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113IC
UT WOS:000316658800036
PM 23451084
ER
PT J
AU Sood, R
Carrington, B
Bishop, K
Jones, M
Rissone, A
Candotti, F
Chandrasekharappa, SC
Liu, P
AF Sood, Raman
Carrington, Blake
Bishop, Kevin
Jones, MaryPat
Rissone, Alberto
Candotti, Fabio
Chandrasekharappa, Settara C.
Liu, Paul
TI Efficient Methods for Targeted Mutagenesis in Zebrafish Using
Zinc-Finger Nucleases: Data from Targeting of Nine Genes Using CompoZr
or CoDA ZFNs
SO PLOS ONE
LA English
DT Article
ID POOL ENGINEERING OPEN; TAL EFFECTORS; GENOME; DNA; TRANSCRIPTION;
INACTIVATION; SELECTION; PROTEINS; MUTATION; PROJECT
AB Recently, it has been shown that targeted mutagenesis using zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) can be used to generate knockout zebrafish lines for analysis of their function and/or developing disease models. A number of different methods have been developed for the design and assembly of gene-specific ZFNs and TALENs, making them easily available to most zebrafish researchers. Regardless of the choice of targeting nuclease, the process of generating mutant fish is similar. It is a time-consuming and multi-step process that can benefit significantly from development of efficient high throughput methods. In this study, we used ZFNs assembled through either the CompoZr (Sigma-Aldrich) or the CoDA (context-dependent assembly) platforms to generate mutant zebrafish for nine genes. We report our improved high throughput methods for 1) evaluation of ZFNs activity by somatic lesion analysis using colony PCR, eliminating the need for plasmid DNA extractions from a large number of clones, and 2) a sensitive founder screening strategy using fluorescent PCR with PIG-tailed primers that eliminates the stutter bands and accurately identifies even single nucleotide insertions and deletions. Using these protocols, we have generated multiple mutant alleles for seven genes, five of which were targeted with CompoZr ZFNs and two with CoDA ZFNs. Our data also revealed that at least five-fold higher mRNA dose was required to achieve mutagenesis with CoDA ZFNs than with CompoZr ZFNs, and their somatic lesion frequency was lower (<5%) when compared to CopmoZr ZFNs (9-98%). This work provides high throughput protocols for efficient generation of zebrafish mutants using ZFNs and TALENs.
C1 [Sood, Raman; Carrington, Blake; Bishop, Kevin] NHGRI, Zebrafish Core Facil, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
[Jones, MaryPat; Chandrasekharappa, Settara C.] NHGRI, Genom Core, Genome Technol Branch, Bethesda, MD 20892 USA.
[Rissone, Alberto; Candotti, Fabio] NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
[Liu, Paul] NHGRI, Oncogenesis & Dev Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
RP Sood, R (reprint author), NHGRI, Zebrafish Core Facil, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
EM rsood@mail.nih.gov
RI Liu, Paul/A-7976-2012
OI Liu, Paul/0000-0002-6779-025X
FU Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health
FX This study was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 45
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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 FEB 22
PY 2013
VL 8
IS 2
AR e57239
DI 10.1371/journal.pone.0057239
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113IC
UT WOS:000316658800094
PM 23451191
ER
PT J
AU Pronk, A
Nuckols, JR
De Roos, AJ
Airola, M
Colt, JS
Cerhan, JR
Morton, L
Cozen, W
Severson, R
Blair, A
Cleverly, D
Ward, MH
AF Pronk, Anjoeka
Nuckols, John R.
De Roos, Anneclaire J.
Airola, Matthew
Colt, Joanne S.
Cerhan, James R.
Morton, Lindsay
Cozen, Wendy
Severson, Richard
Blair, Aaron
Cleverly, David
Ward, Mary H.
TI Residential proximity to industrial combustion facilities and risk of
non-Hodgkin lymphoma: a case-control study
SO ENVIRONMENTAL HEALTH
LA English
DT Article
DE Non-Hodgkin lymphoma; Lymphomas; Dioxins; Air pollution; Geographic
information systems; Case-control study
ID SOLID-WASTE INCINERATOR; SOFT-TISSUE SARCOMA; DIBENZO-P-DIOXINS; PHENOXY
HERBICIDES; CANCER-MORTALITY; FOLLOW-UP; WORKERS; VICINITY; SAMPLES;
SOIL
AB Background: Residence near municipal solid waste incinerators, a major historical source of dioxin emissions, has been associated with increased risk of non-Hodgkin lymphoma (NHL) in European studies. The aim of our study was to evaluate residence near industrial combustion facilities and estimates of dioxin emissions in relation to NHL risk in the United States.
Methods: We conducted a population-based case-control study of NHL (1998-2000) in four National Cancer Institute-Surveillance Epidemiology and End Results centers (Detroit, Iowa, Los Angeles, Seattle). Residential histories 15 years before diagnosis (similar date for controls) were linked to an Environmental Protection Agency database of dioxin-emitting facilities for 969 cases and 749 controls. We evaluated proximity (3 and 5 km) to 10 facility types that accounted for >85% of U. S. emissions and a distance-weighted average emission index (AEI [ng toxic equivalency quotient (TEQ)/year]).
Results: Proximity to any dioxin-emitting facility was not associated with NHL risk (3 km OR = 1.0, 95% CI 0.8-1.3). Risk was elevated for residence near cement kilns (5 km OR = 1.7, 95% CI 0.8-3.3; 3 km OR = 3.8, 95% CI 1.1-14.0) and reduced for residence near municipal solid waste incinerators (5 km OR = 0.5, 95% CI 0.3-0.9; 3 km OR = 0.3, 95% CI 0.1-1.4). The AEI was not associated with risk of NHL overall. Risk for marginal zone lymphoma was increased for the highest versus lowest quartile (5 km OR = 2.6, 95% CI 1.0-6.8; 3 km OR = 3.0, 95% CI 1.1-8.3).
Conclusions: Overall, we found no association with residential exposure to dioxins and NHL risk. However, findings for high emissions and marginal zone lymphoma and for specific facility types and all NHL provide some evidence of an association and deserve future study.
C1 [Pronk, Anjoeka; Colt, Joanne S.; Morton, Lindsay; Blair, Aaron; Ward, Mary H.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD USA.
[Pronk, Anjoeka] TNO, NL-3700 AJ Zeist, Netherlands.
[Nuckols, John R.] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA.
[De Roos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[De Roos, Anneclaire J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Airola, Matthew] Westat Corp, Rockville, MD USA.
[Cerhan, James R.] Mayo Clin, Coll Med, Rochester, MN USA.
[Cozen, Wendy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Cozen, Wendy] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA.
[Cozen, Wendy] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Severson, Richard] Wayne State Univ, Dept Family Med, Detroit, MI USA.
[Severson, Richard] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Cleverly, David] US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA.
[Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Ward, MH (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD USA.
EM wardm@mail.nih.gov
OI Cerhan, James/0000-0002-7482-178X
FU National Institutes of Health, NCI; NCI SEER [N01-PC-65064,
N01-PC-67009, N01-CN-67008, N01-CN-67010]; NCI Occupational and
Environmental Epidemiology Branch; Colorado State University
FX We thank Lonn Tremblay and Nathan Appel of Information Management
Systems, Inc for programming support. We also thank Laura Gold, Robert
Mathes, Hozefa Divan, and Jim Giglierano and his staff at the Iowa
Geologic Survey for their efforts in ground checking residential
locations and Abigail Flory of Westat, Inc. for additional verification
of GPS locations. This study was supported in part by the Intramural
Research Program of the National Institutes of Health, NCI and by NCI
SEER Contracts N01-PC-65064 (Detroit), N01-PC-67009 (Seattle),
N01-CN-67008 (Iowa) and N01-CN-67010 (Los Angeles). John Nuckols was
supported in part, through an intergovernmental personnel agreement
between the NCI Occupational and Environmental Epidemiology Branch and
Colorado State University.
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U2 20
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-069X
J9 ENVIRON HEALTH-GLOB
JI Environ. Health
PD FEB 22
PY 2013
VL 12
AR 20
DI 10.1186/1476-069X-12-20
PG 11
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 108JE
UT WOS:000316288100001
PM 23433489
ER
PT J
AU Bidulescu, A
Liu, JK
Hickson, DA
Hairston, KG
Fox, ER
Arnett, DK
Sumner, AE
Taylor, HA
Gibbons, GH
AF Bidulescu, Aurelian
Liu, Jiankang
Hickson, DeMarc A.
Hairston, Kristen G.
Fox, Ervin R.
Arnett, Donna K.
Sumner, Anne E.
Taylor, Herman A.
Gibbons, Gary H.
TI Gender differences in the association of visceral and subcutaneous
adiposity with adiponectin in African Americans: the Jackson Heart Study
SO BMC CARDIOVASCULAR DISORDERS
LA English
DT Article
ID BODY-FAT DISTRIBUTION; INSULIN-RESISTANCE; METABOLIC SYNDROME;
RISK-FACTORS; SERUM ADIPONECTIN; PLASMA ADIPONECTIN; YOUNG-ADULTS;
TISSUE; OBESITY; WOMEN
AB Background: Adiponectin, paradoxically reduced in obesity and with lower levels in African Americans (AA), modulates several cardiometabolic risk factors. Because abdominal visceral adipose tissue (VAT), known to be reduced in AA, and subcutaneous adipose tissue (SAT) compartments may confer differential metabolic risk profiles, we investigated the associations of VAT and SAT with serum adiponectin, separately by gender, with the hypothesis that VAT is more strongly inversely associated with adiponectin than SAT.
Methods: Participants from the Jackson Heart Study, an ongoing cohort of AA (n = 2,799; 64% women; mean age, 55 +/- 11 years) underwent computer tomography assessment of SAT and VAT volumes, and had stored serum specimens analyzed for adiponectin levels. These levels were examined by gender in relation to increments of VAT and SAT.
Results: Compared to women, men had significantly lower mean levels of adiponectin (3.9 +/- 3.0 mu g/mL vs. 6.0 +/- 4.4 mu g/mL; p < 0.01) and mean volume of SAT (1,721 +/- 803 cm(3) vs. 2,668 +/- 968 cm(3); p < 0.01) but significantly higher mean volume of VAT (884 +/- 416 cm(3) vs. 801 +/- 363 cm(3); p < 0.01). Among women, a one standard deviation increment in VAT was inversely associated with adiponectin (beta = -0.13; p < 0.0001) after controlling for age, systolic blood pressure, fasting plasma glucose, high-density lipoprotein cholesterol, triglycerides, education, pack-years of smoking and daily intake of alcohol. The statistically significant inverse association of VAT and adiponectin persisted after additionally adjusting for SAT, body mass index (BMI) and waist circumference (WC), suggesting that VAT provides significant information above and beyond BMI and WC. Among men, after the same multivariable adjustment, there was a direct association of SAT and adiponectin (beta = 0.18; p = 0.002) that persisted when controlling for BMI and WC, supporting a beneficial effect of SAT. Insulin resistance mediated the association of SAT with adiponectin in women.
Conclusion: In African Americans, abdominal visceral adipose tissue had an inverse association with serum adiponectin concentrations only among women. Abdominal subcutaneous adipose tissue appeared as a protective fat depot in men.
C1 [Bidulescu, Aurelian] Morehouse Sch Med, Dept Community Hlth & Prevent Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA.
[Liu, Jiankang; Hickson, DeMarc A.; Fox, Ervin R.; Taylor, Herman A.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39213 USA.
[Hairston, Kristen G.] Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Sect Endocrinol & Metab, Winston Salem, NC 27157 USA.
[Hickson, DeMarc A.; Taylor, Herman A.] Jackson State Univ, Jackson Heart Study, Jackson, MS 39217 USA.
[Arnett, Donna K.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA.
[Sumner, Anne E.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Gibbons, Gary H.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Bidulescu, A (reprint author), Morehouse Sch Med, Dept Community Hlth & Prevent Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA.
EM abidulescu@msm.edu
RI Bidulescu, Aurelian/N-2617-2014
OI Bidulescu, Aurelian/0000-0001-8211-8309
FU Jackson State University [N01-HC-95170]; University of Mississippi
Medical Center [N01-HC-95171]; Tougaloo College [N01-HC-95172]; NIH from
the National Heart, Lung, and Blood Institute (NHLBI); National Center
on Minority Health and Health Disparities (NCMHD); NHLBI [HL076784];
National Institute of Aging [AG028321]; PHS from the National Institutes
of Health, National Center for Research Resources [UL1 RR025008]; NIH
National Heart, Lung and Blood Institute [UH1 HL073461]; NIDDK/NIH
FX The Jackson Heart Study is supported and conducted in collaboration with
Jackson State University (N01-HC-95170), University of Mississippi
Medical Center (N01-HC-95171), and Tougaloo College (N01-HC-95172) NIH
contracts from the National Heart, Lung, and Blood Institute (NHLBI) and
the National Center on Minority Health and Health Disparities (NCMHD)
with additional support from NHLBI contract HL076784 and the National
Institute of Aging (AG028321).; This study was partially supported by
PHS Award UL1 RR025008 from the National Institutes of Health, National
Center for Research Resources to the first author (A. B.) who was also
supported by the NIH grant UH1 HL073461 provided by the National Heart,
Lung and Blood Institute.; The intramural program of NIDDK/NIH supported
one of the authors (A. E. S). The results described in this article have
been presented in part during the American Heart Association Scientific
Sessions Conference, November 2011 in Orlando, Florida.
NR 50
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Z9 20
U1 0
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2261
J9 BMC CARDIOVASC DISOR
JI BMC Cardiovasc. Disord.
PD FEB 22
PY 2013
VL 13
AR 9
DI 10.1186/1471-2261-13-9
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 101JR
UT WOS:000315771800001
PM 23433085
ER
PT J
AU Nanda, JS
Saini, AK
Munoz, AM
Hinnebusch, AG
Lorsch, JR
AF Nanda, Jagpreet S.
Saini, Adesh K.
Munoz, Antonio M.
Hinnebusch, Alan G.
Lorsch, Jon R.
TI Coordinated Movements of Eukaryotic Translation Initiation Factors eIF1,
eIF1A, and eIF5 Trigger Phosphate Release from eIF2 in Response to Start
Codon Recognition by the Ribosomal Preinitiation Complex
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID C-TERMINAL DOMAIN; SELECTION IN-VIVO; SITE SELECTION; MULTIFACTOR
COMPLEX; CRYSTAL-STRUCTURE; GTP HYDROLYSIS; AUG SELECTION; SUBUNIT;
REVEALS; BINDING
AB Accurate recognition of the start codon in an mRNA by the eukaryotic translation preinitiation complex (PIC) is essential for proper gene expression. The process is mediated by eukaryotic translation initiation factors (eIFs) in conjunction with the 40 S ribosomal subunit and (initiator) tRNA(i). Here, we provide evidence that the C-terminal tail (CTT) of eIF1A, which we previously implicated in start codon recognition, moves closer to the N-terminal domain of eIF5 when the PIC encounters an AUG codon. Importantly, this movement is coupled to dissociation of eIF1 from the PIC, a critical event in start codon recognition, and is dependent on the scanning enhancer elements in the eIF1A CTT. The data further indicate that eIF1 dissociation must be accompanied by the movement of the eIF1A CTT toward eIF5 in order to trigger release of phosphate from eIF2, which converts the latter to its GDP-bound state. Our results also suggest that release of eIF1 from the PIC and movement of the CTT of eIF1A are triggered by the same event, most likely accommodation of tRNA(i) in the P site of the 40 S subunit driven by base pairing between the start codon in the mRNA and the anticodon in tRNA(i). Finally, we show that the C-terminal domain of eIF5 is responsible for the factor's activity in antagonizing eIF1 binding to the PIC. Together, our data provide a more complete picture of the chain of molecular events that is triggered when the scanning PIC encounters an AUG start codon in the mRNA.
C1 [Nanda, Jagpreet S.; Munoz, Antonio M.; Lorsch, Jon R.] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
[Saini, Adesh K.; Hinnebusch, Alan G.] Eunice K Shriver NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Lorsch, JR (reprint author), Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, 725 N Wolfe St, Baltimore, MD 21205 USA.
EM jlorsch@jhmi.edu
RI university, shoolini/K-9336-2015;
OI Lorsch, Jon/0000-0002-4521-4999
FU National Institutes of Health [GM 62128]; National Institutes of Health
Intramural Research Program
FX This work was supported, in whole or in part, by National Institutes of
Health Grants GM 62128 (to J.R.L.) and by the National Institutes of
Health Intramural Research Program (to A.G.H.).
NR 43
TC 28
Z9 29
U1 0
U2 8
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 FEB 22
PY 2013
VL 288
IS 8
BP 5316
EP 5329
DI 10.1074/jbc.M112.440693
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 095NY
UT WOS:000315342500006
PM 23293029
ER
PT J
AU Chen, PW
Jian, XY
Yoon, HY
Randazzo, PA
AF Chen, Pei-Wen
Jian, Xiaoying
Yoon, Hye-Young
Randazzo, Paul A.
TI ARAP2 Signals through Arf6 and Rac1 to Control Focal Adhesion Morphology
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ADP-RIBOSYLATION FACTOR; GTPASE-ACTIVATING-PROTEIN; CELL-MIGRATION;
ACTIN CYTOSKELETON; DOWNSTREAM ACTIVATION; LEADING-EDGE; RHO GTPASES;
COMPLEX; DYNAMICS; MICROTUBULE
AB Focal adhesions (FAs) are dynamic structures that connect the actin cytoskeleton with the extracellular matrix. At least six ADP-ribosylation factor (Arf) GTPase-activating proteins (GAPs), including ARAP2 (an Arf6 GAP), are implicated in regulation of FAs but the mechanisms for most are not well defined. Although Rac1 has been reported to function downstream of Arf6 to control membrane ruffling and cell migration, this pathway has not been directly examined as a regulator of FAs. Here we test the hypothesis that ARAP2 promotes the growth of FAs by converting Arf6.GTP to Arf6.GDP thereby preventing the activation of the Rho family GTP-binding protein Rac1. Reduced expression of ARAP2 decreased the number and size of FAs in cells and increased cellular Arf6.GTP and Rac1.GTP levels. Overexpression of ARAP2 had the opposite effects. The effects of ARAP2 on FAs and Rac1 were dependent on a functional ArfGAP domain. Constitutively active Arf6 affected FAs in the same way as did reduced ARAP2 expression and dominant negative mutants of Arf6 and Rac1 reversed the effect of reduced ARAP2 expression. However, neither dominant negative Arf6 nor Rac1 had the same effect as ARAP2 overexpression. We conclude that changes in Arf6 and Rac1 activities are necessary but not sufficient for ARAP2 to promote the growth of FAs and we speculate that ARAP2 has additional functions that are effector in nature to promote or stabilize FAs.
C1 [Chen, Pei-Wen; Jian, Xiaoying; Yoon, Hye-Young; Randazzo, Paul A.] NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Randazzo, PA (reprint author), NCI, Lab Cellular & Mol Biol, Bldg 37 Room 2042, Bethesda, MD 20892 USA.
EM randazzp@mail.nih.gov
RI Chen, Pei-Wen/B-7142-2015
FU NCI, National Institutes of Health [BC 007365]
FX This work was supported, in whole or in part, by the intramural program
of the NCI, National Institutes of Health (Project BC 007365).
NR 71
TC 9
Z9 9
U1 1
U2 18
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 FEB 22
PY 2013
VL 288
IS 8
BP 5849
EP 5860
DI 10.1074/jbc.M112.415778
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 095NY
UT WOS:000315342500055
PM 23295182
ER
PT J
AU Hosokawa, H
Dip, PV
Merkulova, M
Bakulina, A
Zhuang, ZJ
Khatri, A
Jian, XY
Keating, SM
Bueler, SA
Rubinstein, JL
Randazzo, PA
Ausiello, DA
Gruber, G
Marshansky, V
AF Hosokawa, Hiroyuki
Dip, Phat Vinh
Merkulova, Maria
Bakulina, Anastasia
Zhuang, Zhenjie
Khatri, Ashok
Jian, Xiaoying
Keating, Shawn M.
Bueler, Stephanie A.
Rubinstein, John L.
Randazzo, Paul A.
Ausiello, Dennis A.
Grueber, Gerhard
Marshansky, Vladimir
TI The N Termini of a-Subunit Isoforms Are Involved in Signaling between
Vacuolar H+-ATPase (V-ATPase) and Cytohesin-2
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NUCLEOTIDE EXCHANGE FACTOR; CIRCULAR-DICHROISM SPECTRA; PROTEIN
SECONDARY STRUCTURE; VESICULAR TRAFFICKING; ARF ACTIVATION; PROTON
PUMPS; FACTOR ARNO; PH-SENSOR; RECEPTOR; A2-SUBUNIT
AB Previously, we reported an acidification-dependent interaction of the endosomal vacuolar H+-ATPase (V-ATPase) with cytohesin-2, a GDP/GTP exchange factor (GEF), suggesting that it functions as a pH-sensing receptor. Here, we have studied the molecular mechanism of signaling between the V-ATPase, cytohesin-2, and Arf GTP-binding proteins. We found that part of the N-terminal cytosolic tail of the V-ATPase a2-subunit (a2N), corresponding to its first 17 amino acids (a2N(1-17)), potently modulates the enzymatic GDP/GTP exchange activity of cytohesin-2. Moreover, this peptide strongly inhibits GEF activity via direct interaction with the Sec7 domain of cytohesin-2. The structure of a2N(1-17) and its amino acids Phe(5), Met(10), and Gln(14) involved in interaction with Sec7 domain were determined by NMR spectroscopy analysis. In silico docking experiments revealed that part of the V-ATPase formed by its a2N(1-17) epitope competes with the switch 2 region of Arf1 and Arf6 for binding to the Sec7 domain of cytohesin-2. The amino acid sequence alignment and GEF activity studies also uncovered the conserved character of signaling between all four (a1-a4) a-subunit isoforms of mammalian V-ATPase and cytohesin-2. Moreover, the conserved character of this phenomenon was also confirmed in experiments showing binding of mammalian cytohesin-2 to the intact yeast V-ATPase holo-complex. Thus, here we have uncovered an evolutionarily conserved function of the V-ATPase as a novel cytohesin-signaling receptor.
C1 [Hosokawa, Hiroyuki; Merkulova, Maria; Zhuang, Zhenjie; Ausiello, Dennis A.; Marshansky, Vladimir] Massachusetts Gen Hosp, Simches Res Ctr, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA.
[Hosokawa, Hiroyuki; Merkulova, Maria; Zhuang, Zhenjie; Ausiello, Dennis A.; Marshansky, Vladimir] Massachusetts Gen Hosp, Simches Res Ctr, Div Nephrol, Boston, MA 02114 USA.
[Ausiello, Dennis A.; Marshansky, Vladimir] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
[Dip, Phat Vinh; Grueber, Gerhard] Nanyang Technol Univ, Sch Biol Sci, Div Struct Biol & Biochem, Singapore 637551, Singapore.
[Bakulina, Anastasia] State Res Ctr Virol & Biotechnol VECTOR, Koltsov 630559, Novosibirsk Reg, Russia.
[Khatri, Ashok] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Khatri, Ashok] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Jian, Xiaoying; Randazzo, Paul A.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Keating, Shawn M.; Bueler, Stephanie A.; Rubinstein, John L.] Hosp Sick Children, Res Inst, Mol Struct & Funct Program, Toronto, ON M5G 1X8, Canada.
[Keating, Shawn M.; Rubinstein, John L.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1X8, Canada.
RP Marshansky, V (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA.
EM Marshansky.Vladimir@mgh.harvard.edu
RI Bakulina, Anastasia/A-6215-2014;
OI Dip, Phat Vinh/0000-0002-1535-9644; Rubinstein, John/0000-0003-0566-2209
FU National Institutes of Health Grant [DK038452, DK57521]; Boston Area
Diabetes Endocrinology Research Center Grant [DK057521-08]; National
Institutes of Health Intramural Program of NCI; Canadian Institutes of
Health Research Grant [MOP 81294]; A*STAR Biomedical Research Council
Grant [09/1/22/19/609]; Center for the Study of Inflammatory Bowel
Disease [DK43351]; Singapore International Graduate Award (SINGA)
[20092010S10303]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant DK038452. This work was also supported by Boston Area
Diabetes Endocrinology Research Center Grant DK057521-08 (to V. M.).;
Recipient of a Singapore International Graduate Award (SINGA,
20092010S10303).; Supported by the National Institutes of Health
Intramural Program of NCI.; Supported by Canadian Institutes of Health
Research Grant MOP 81294.; Supported by A*STAR Biomedical Research
Council Grant 09/1/22/19/609.; We thank Dr. Dennis Brown for critical
reading and constructive suggestions during the preparation of this
manuscript. We are grateful to Dr. Masamitsu Futai and Dr. James
Casanova for providing cDNA encoding V-ATPase a2-isoform and
cytohesin-2, respectively. We are also grateful to Dr. Sylvain Bourgoin
for the generous gift of SecinH3 inhibitor. The Microscopy Core Facility
of the Program in Membrane Biology received additional support from
National Institutes of Health Grant DK57521 to BADERC and Grant DK43351
to Center for the Study of Inflammatory Bowel Disease.
NR 68
TC 21
Z9 21
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 FEB 22
PY 2013
VL 288
IS 8
BP 5896
EP 5913
DI 10.1074/jbc.M112.409169
PG 18
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 095NY
UT WOS:000315342500059
PM 23288846
ER
PT J
AU Van Duyne, R
Guendel, I
Jaworski, E
Sampey, G
Klase, Z
Chen, H
Zeng, C
Kovalskyy, D
el Kouni, MH
Lepene, B
Patanarut, A
Nekhai, S
Price, DH
Kashanchi, F
AF Van Duyne, Rachel
Guendel, Irene
Jaworski, Elizabeth
Sampey, Gavin
Klase, Zachary
Chen, Hao
Zeng, Chen
Kovalskyy, Dmytro
el Kouni, Mahmoud H.
Lepene, Benjamin
Patanarut, Alexis
Nekhai, Sergei
Price, David H.
Kashanchi, Fatah
TI Effect of Mimetic CDK9 Inhibitors on HIV-1-Activated Transcription
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE ATP analog; CDK9; cyclin T1; viral transactivator; inhibitors
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RNA-POLYMERASE-II; P-TEFB; HIV-1 TAT;
CDK9/CYCLIN T1; BINDING; REPLICATION; COMPLEXES; CELLS; IDENTIFICATION
AB Potent anti-retroviral therapy has transformed HIV-1 infection into a chronic manageable disease; however, drug resistance remains a common problem that limits the effectiveness and clinical benefits of this type of treatment. The discovery of viral reservoirs in the body, in which HIV-1 may persist, has helped to explain why therapeutic eradication of HIV-1 has proved so difficult. In the current study, we utilized a combination of structure-based analysis of cyclin/CDK complexes with our previously published Tat peptide derivatives. We modeled the Tat peptide inhibitors with CDKs and found a particular pocket that showed the most stable binding site (Cavity 1) using in silico analysis. Furthermore, we were able to find peptide mimetics that bound to similar regions using in silico searches of a chemical library, followed by cell-based biological assays. Using these methods, we obtained the first-generation mimetic drugs and tested these compounds on HIV-1 long terminal repeat-activated transcription. Using biological assays followed by similar in silico analysis to find second-generation drugs resembling the original mimetic, we found the new targets of Cavity 1 and Cavity 2 regions on CDK9. We examined the second-generation mimetic against various viral isolates and observed a generalized suppression of most HIV-1 isolates. Finally, the drug inhibited viral replication in humanized mouse models of Rag2(-/-)gamma c(-/-) with no toxicity to the animals at tested concentrations. Our results suggest that it may be possible to model peptide inhibitors into available crystal structures and further find drug mimetics using in silico analysis. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Van Duyne, Rachel; Guendel, Irene; Jaworski, Elizabeth; Sampey, Gavin; Kashanchi, Fatah] George Mason Univ, Natl Ctr Biodef & Infect Dis, Manassas, VA 20110 USA.
[Van Duyne, Rachel] George Washington Univ, Med Ctr, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA.
[Klase, Zachary] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Hao; Zeng, Chen] George Washington Univ, Dept Phys, Washington, DC 20052 USA.
[Zeng, Chen] Huazhong Univ Sci & Technol, Dept Phys, Wuhan 430074, Peoples R China.
[Kovalskyy, Dmytro] Ukrainian Acad Sci, Inst Mol Biol & Genet, Dept Prot Engn, UA-252627 Kiev, Ukraine.
[el Kouni, Mahmoud H.] Univ Alabama Birmingham, Ctr AIDS Res, Ctr Comprehens Canc, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA.
[Lepene, Benjamin; Patanarut, Alexis] Ceres Nanosci Inc, Manassas, VA 20110 USA.
[Nekhai, Sergei] Howard Univ, Ctr Sickle Cell Dis, Dept Med, Washington, DC 20060 USA.
[Price, David H.] Univ Iowa, Interdisciplinary Mol Biol Program, Dept Biochem, Iowa City, IA 52242 USA.
RP Kashanchi, F (reprint author), George Mason Univ, Natl Ctr Biodef & Infect Dis, Discovery Hall,Room 182,10900 Univ Blvd MS 1H8, Manassas, VA 20110 USA.
EM fkashanc@gmu.edu
FU GMU; NIH [AI043894, AI078859, AI074410]
FX We would like to thank the members of the Kashanchi laboratory for
experiments and assistance with the manuscript. Further support came
from grants from the GMU funds to F.K. and NIH grants AI043894,
AI078859, and AI074410. Rachel Van Duyne is a predoctoral student in the
Microbiology and Immunology Program of the Institute for Biomedical
Sciences at the George Washington University. This work is from a
dissertation to be presented to the above program in partial fulfillment
of the requirements for the Ph.D. degree.
NR 29
TC 14
Z9 14
U1 0
U2 9
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD FEB 22
PY 2013
VL 425
IS 4
BP 812
EP 829
DI 10.1016/j.jmb.2012.12.005
PG 18
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 098JV
UT WOS:000315546500011
PM 23247501
ER
PT J
AU Singh, NS
Paul, RK
Torjman, MC
Wainer, IW
AF Singh, Nagendra S.
Paul, Rajib K.
Torjman, Marc C.
Wainer, Irving W.
TI Gabapentin and (S)-pregabalin decrease intracellular D-serine
concentrations in PC-12 cells
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE D-Serine; Serine racemase; Neuropathic pain; N-Methyl D-aspartate
receptor; Gabapentin; (S)-pregabalin
ID AMINO-ACID OXIDASE; RANDOMIZED CONTROLLED-TRIAL; SENSITIVE CA2+
CHANNELS; NEUROPATHIC PAIN; RAT-BRAIN; MESSENGER-RNAS; RACEMASE;
CALCIUM; MECHANISMS; EXPRESSION
AB The effects of gabapentin (GBP) and (S)-pregabalin (PGB) on the intracellular concentrations of D-serine and the expression of serine racemase (SR) in PC-12 cells were determined. Intracellular D-serine concentrations were determined using an enantioselective capillary electrophoresis assay with laser-induced fluorescence detection. Increasing concentrations of GBP, 0.1-20 mu M, produced a significant decrease in D-serine concentration relative to control, 22.9 +/- 6.7% at 20 mu M (*p < 0.05), with an IC50 value of 3.40 +/- 10.29 mu M. Increasing concentrations of PGB, 0.1-10 mu M, produced a significant decrease in D-serine concentration relative to control, 25.3 +/- 17.6% at 10 mu M (*p < 0.05), with an IC50 value of 3.38 +/- 10.21 mu M. The compounds had no effect on the expression of monomeric-SR or dimeric-SR as determined by Western blotting. The results suggest that incubation of PC-12 cells with GBP and PGB reduced the basal activity of SR, which is most likely a result of the decreased Ca2+ flux produced via interaction of the drugs with the alpha(2)-delta subunit of voltage-gated calcium channels. D-Serine is a co-agonist of the N-methyl D-aspartate receptor (NMDAR) and reduced D-serine concentrations have been associated with reduced NMDAR activity. Thus, GBP and PGB may act as indirect antagonists of NMDAR, a mechanism that may contribute to the clinical effects of the drugs in neuropathic pain. Published by Elsevier Ireland Ltd.
C1 [Singh, Nagendra S.; Paul, Rajib K.; Wainer, Irving W.] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA.
[Torjman, Marc C.] Rowan Univ, Cooper Med Sch, Biostat Grp, Camden, NJ 08103 USA.
RP Wainer, IW (reprint author), NIA, Lab Clin Invest, NIH, Biomed Res Ctr, 251 Bayview Boul,Suite 100,Room 088133, Baltimore, MD 21224 USA.
EM WainerIr@grc.nia.nih.gov
RI Singh, Nagendra/K-8966-2015
FU Intramural Research Program of the National Institute on Aging/NIH
FX This work was supported by funding from the Intramural Research Program
of the National Institute on Aging/NIH.
NR 31
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Z9 7
U1 0
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD FEB 22
PY 2013
VL 535
BP 90
EP 94
DI 10.1016/j.neulet.2012.12.024
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 095XK
UT WOS:000315368100017
PM 23274708
ER
PT J
AU Chiyaka, C
Tatem, AJ
Cohen, JM
Gething, PW
Johnston, G
Gosling, R
Laxminarayan, R
Hay, SI
Smith, DL
AF Chiyaka, C.
Tatem, A. J.
Cohen, J. M.
Gething, P. W.
Johnston, G.
Gosling, R.
Laxminarayan, R.
Hay, S. I.
Smith, D. L.
TI The Stability of Malaria Elimination
SO SCIENCE
LA English
DT Editorial Material
ID FEASIBILITY; POPULATION; STRATEGIES
C1 [Chiyaka, C.; Tatem, A. J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32610 USA.
[Tatem, A. J.] Univ Southampton, Dept Geog & Environm, Southampton SO17 1BJ, Hants, England.
[Tatem, A. J.; Hay, S. I.; Smith, D. L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Cohen, J. M.] Clinton Hlth Access Initiat, Boston, MA 02127 USA.
[Gething, P. W.; Hay, S. I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
[Johnston, G.; Smith, D. L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Johnston, G.; Smith, D. L.] Johns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, Baltimore, MD 21205 USA.
[Gosling, R.] Univ Calif San Francisco, Malaria Eliminat Initiat, Global Hlth Grp, San Francisco, CA 94105 USA.
[Hay, S. I.; Smith, D. L.] Ctr Dis Dynam Econ & Policy, Washington, DC 20036 USA.
RP Smith, DL (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM dlsmith@jhsph.edu
RI Smith, David/L-8850-2013; Hay, Simon/F-8967-2015;
OI Smith, David/0000-0003-4367-3849; Hay, Simon/0000-0002-0611-7272;
Gething, Peter/0000-0001-6759-5449
FU Medical Research Council [MR/K00669X/1]; NIAID NIH HHS [U19AI089674];
Wellcome Trust [095066]
NR 25
TC 26
Z9 26
U1 0
U2 18
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 FEB 22
PY 2013
VL 339
IS 6122
BP 909
EP 910
DI 10.1126/science.1229509
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092UX
UT WOS:000315149600032
PM 23430640
ER
PT J
AU Salaverria, I
Royo, C
Carvajal-Cuenca, A
Clot, G
Navarro, A
Valera, A
Song, JY
Woroniecka, R
Rymkiewicz, G
Klapper, W
Hartmann, EM
Sujobert, P
Wlodarska, I
Ferry, JA
Gaulard, P
Ott, G
Rosenwald, A
Lopez-Guillermo, A
Quintanilla-Martinez, L
Harris, NL
Jaffe, ES
Siebert, R
Campo, E
Bea, S
AF Salaverria, Itziar
Royo, Cristina
Carvajal-Cuenca, Alejandra
Clot, Guillem
Navarro, Alba
Valera, Alejandra
Song, Joo Y.
Woroniecka, Renata
Rymkiewicz, Grzegorz
Klapper, Wolfram
Hartmann, Elena M.
Sujobert, Pierre
Wlodarska, Iwona
Ferry, Judith A.
Gaulard, Philippe
Ott, German
Rosenwald, Andreas
Lopez-Guillermo, Armando
Quintanilla-Martinez, Leticia
Harris, Nancy L.
Jaffe, Elaine S.
Siebert, Reiner
Campo, Elias
Bea, Silvia
TI CCND2 rearrangements are the most frequent genetic events in cyclin
D1(-) mantle cell lymphoma
SO BLOOD
LA English
DT Article
ID NUCLEAR EXPRESSION; SOX11 EXPRESSION; GENOME; TARGET; OVEREXPRESSION;
AMPLIFICATIONS; TRANSLOCATION; PATHOGENESIS; NEOPLASMS; DIAGNOSIS
AB Cyclin D1(-) mantle cell lymphomas (MCLs) are not well characterized, in part because of the difficulties in their recognition. SOX11 has been identified recently as a reliable biomarker of MCL that is also expressed in the cyclin D1(-) variant. We investigated 40 lymphomas with MCL morphology and immunophenotype that were negative for cyclin D1 expression/t(11;14)(q13;q32) but positive for SOX11. These tumors presented clinically with generalized lymphadenopathy, advanced stage, and poor outcome (5-year overall survival, 48%). Chromosomal rearrangements of the CCND2 locus were detected in 55% of the cases, with an IG gene as partner in 18 of 22, in particular with light chains (10 IGK@ and 5 IGL@). No mutations in the phosphorylation motifs of CCND1, CCND2, or CCND3 were detected. The global genomic profile and the high complexity of the 32 cyclin D1(-)SOX11(+) MCL patients analyzed by copy number arrays were similar to the conventional cyclin D1(+)/SOX11(+) MCL. 17p deletions and high Ki67 expression conferred a significantly worse outcome for the patients. This comprehensive characterization of a large series of cyclin D1(-) MCL patients indicates that these tumors are clinically and biologically similar to the conventional cyclin D1(+) MCL and provides a basis for the proper identification and clinical management of these patients.
C1 [Salaverria, Itziar; Royo, Cristina; Carvajal-Cuenca, Alejandra; Clot, Guillem; Navarro, Alba; Valera, Alejandra; Campo, Elias; Bea, Silvia] Univ Barcelona, Inst Invest Biomed August Pi & Sunyer, Dept Pathol, Hematopathol Unit,Hosp Clin, Barcelona, Spain.
[Salaverria, Itziar; Siebert, Reiner] Univ Kiel, Univ Hosp Schleswig Holstein Campus Kiel, Inst Human Genet, Kiel, Germany.
[Song, Joo Y.; Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Woroniecka, Renata] Maria Sklodowska Curie Mem Inst & Oncol Ctr, Cytogenet Lab, Warsaw, Poland.
[Rymkiewicz, Grzegorz] Maria Sklodowska Curie Mem Inst & Oncol Ctr, Dept Pathol, Warsaw, Poland.
[Klapper, Wolfram] Univ Kiel, Hematopathol Sect, Dept Pathol, Kiel, Germany.
[Klapper, Wolfram] Univ Kiel, Lymph Node Registry, Kiel, Germany.
[Hartmann, Elena M.; Rosenwald, Andreas] Univ Wurzburg, Inst Pathol, Wurzburg, Germany.
[Sujobert, Pierre; Gaulard, Philippe] Hop Henri Mondor, F-94010 Creteil, France.
[Wlodarska, Iwona] Katholieke Univ Leuven, Ctr Human Genet, Louvain, Belgium.
[Ferry, Judith A.; Harris, Nancy L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany.
[Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.
[Lopez-Guillermo, Armando] Hosp Clin Barcelona, Hematopathol Unit, Dept Hematol, Barcelona, Spain.
[Quintanilla-Martinez, Leticia] Univ Tubingen, Inst Pathol, Tubingen, Germany.
RP Bea, S (reprint author), Ctr Esther Koplowitz, 2nd Floor,Rossello 153, Barcelona 08036, Spain.
EM sbea@clinic.cat
RI Siebert, Reiner/A-8049-2010; Navarro, Alba/H-2611-2015; Royo,
Cristina/H-3193-2015; SALAVERRIA, ITZIAR/L-2246-2015; Song,
Joo/E-5356-2016; Jaffe, Elaine/G-8984-2014; Klapper,
Wolfram/S-6314-2016; Bea, Silvia/K-7699-2014;
OI Navarro, Alba/0000-0002-4041-0974; Royo, Cristina/0000-0002-1214-4656;
SALAVERRIA, ITZIAR/0000-0002-2427-9822; Song, Joo/0000-0003-3497-2513;
Jaffe, Elaine/0000-0003-4632-0301; Bea, Silvia/0000-0001-7192-2385;
Campo, elias/0000-0001-9850-9793
FU Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias
[PI08/0077, PI11/01177]; Alexander von Humboldt Foundation; Subprograma
Juan de la Cierva Ministerio de Ciencia e Innovacion [JCI-2011-10232];
Instituto de Salud Carlos III, Beca Predoctoral de Formacion en
Investigacion en Salud Comision Interministerial de Ciencia y Tecnologia
Espanola [FI08/00347, SAF08/3630]; Red Tematica de Investigacion
Cooperativa del Cancer [RD06/0020/0039 ISCIII]; Spanish Ministry of
Science and Innovation; European Regional Development Fund (Unio Europea
"Una manera de fer Europa")
FX This study was supported by the Instituto de Salud Carlos III, Fondo de
Investigaciones Sanitarias (PI08/0077; PI11/01177 to S. B.), Alexander
von Humboldt Foundation (to I. S.) and Subprograma Juan de la Cierva
Ministerio de Ciencia e Innovacion (JCI-2011-10232 to I. S.), Instituto
de Salud Carlos III, Beca Predoctoral de Formacion en Investigacion en
Salud (FI08/00347 to C. R.) Comision Interministerial de Ciencia y
Tecnologia Espanola (SAF08/3630 to E. C.), Red Tematica de Investigacion
Cooperativa del Cancer (RD06/0020/0039 ISCIII to E. C.), and the Spanish
Ministry of Science and Innovation and European Regional Development
Fund (Unio Europea "Una manera de fer Europa").
NR 33
TC 36
Z9 39
U1 1
U2 10
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 FEB 21
PY 2013
VL 121
IS 8
BP 1394
EP 1402
DI 10.1182/blood-2012-08-452284
PG 9
WC Hematology
SC Hematology
GA 182NK
UT WOS:000321750000024
PM 23255553
ER
PT J
AU Li, ZJ
Zhang, ZY
Li, YY
Arnovitz, S
Chen, P
Huang, H
Jiang, X
Hong, GM
Kunjamma, RB
Ren, HM
He, CJ
Wang, CZ
Elkahloun, AG
Valk, PJM
Dohner, K
Neilly, MB
Bullinger, L
Delwel, R
Lowenberg, B
Liu, PP
Morgan, R
Rowley, JD
Yuan, CS
Chen, JJ
AF Li, Zejuan
Zhang, Zhiyu
Li, Yuanyuan
Arnovitz, Stephen
Chen, Ping
Huang, Hao
Jiang, Xi
Hong, Gia-Ming
Kunjamma, Rejani B.
Ren, Haomin
He, Chunjiang
Wang, Chong-Zhi
Elkahloun, Abdel G.
Valk, Peter J. M.
Doehner, Konstanze
Neilly, Mary Beth
Bullinger, Lars
Delwel, Ruud
Lowenberg, Bob
Liu, Paul P.
Morgan, Richard
Rowley, Janet D.
Yuan, Chun-Su
Chen, Jianjun
TI PBX3 is an important cofactor of HOXA9 in leukemogenesis
SO BLOOD
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; GENE-EXPRESSION PROFILE; REARRANGED
ACUTE-LEUKEMIA; DNA-BINDING; TRANSCRIPTION FACTORS; HEMATOPOIETIC-CELLS;
PROGNOSTIC IMPACT; DOWN-REGULATION; NPM1 MUTATIONS; HOMEOBOX GENES
AB Although PBX proteins are known to increase DNA-binding/transcriptional activity of HOX proteins through their direct binding, the functional importance of their interaction in leukemogenesis is unclear. We recently reported that overexpression of a 4-homeoboxgene signature (ie, PBX3/HOXA7/HOXA9/HOXA11) is an independent predictor of poor survival in patients with cytogenetically abnormal acute myeloid leukemia (CA-AML). Here we show that it is PBX3, but not PBX1 or PBX2, that is consistently coexpressed with HOXA9 in various subtypes of CA-AML, particularly MLL-rearranged AML, and thus appears as a potential pathologic cofactor of HOXA9 in CA-AML. We then show that depletion of endogenous Pbx3 expression by shRNA significantly inhibits MLL-fusion-mediated cell transformation, and coexpressed PBX3 exhibits a significantly synergistic effect with HOXA9 in promoting cell transformation in vitro and leukemogenesis in vivo. Furthermore, as a proof of concept, we show that a small peptide, namely HXR9, which was developed to specifically disrupt the interactions between HOX and PBX proteins, can selectively kill leukemic cells with overexpression of HOXA/PBX3 genes. Collectively, our data suggest that PBX3 is a critical cofactor of HOXA9 in leukemogenesis, and targeting their interaction is a feasible strategy to treat presently therapy resistant CA-AML (eg, MLL-rearranged leukemia) in which HOXA/PBX3 genes are overexpressed. (Blood. 2013;121(8):1422-1431)
C1 [Li, Zejuan; Li, Yuanyuan; Arnovitz, Stephen; Chen, Ping; Huang, Hao; Jiang, Xi; Hong, Gia-Ming; Kunjamma, Rejani B.; Ren, Haomin; He, Chunjiang; Neilly, Mary Beth; Rowley, Janet D.; Chen, Jianjun] Univ Chicago, Dept Med, Sect Hematol Oncol, Chicago, IL 60637 USA.
[Zhang, Zhiyu; Wang, Chong-Zhi; Yuan, Chun-Su] Univ Chicago, Tang Ctr Herbal Med Res, Chicago, IL 60637 USA.
[Elkahloun, Abdel G.; Liu, Paul P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Valk, Peter J. M.; Delwel, Ruud; Lowenberg, Bob] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands.
[Doehner, Konstanze; Bullinger, Lars] Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany.
[Morgan, Richard] Univ Surrey, Postgrad Med Sch, Fac Hlth & Med Sci, Guildford GU2 5XH, Surrey, England.
RP Chen, JJ (reprint author), Univ Chicago, Dept Med, 900 E 57th St,KCBD Rm 7134, Chicago, IL 60637 USA.
EM zjli@uchicago.edu; jchen@medicine.bsd.uchicago.edu
RI Liu, Paul/A-7976-2012;
OI Liu, Paul/0000-0002-6779-025X; He, Chunjiang/0000-0002-4868-331X
FU Leukemia & Lymphoma Society; National Institutes of Health (NIH)
[CA127277]; American Cancer Society (ACS); G. Harold and Leila Y.
Mathers Charitable Foundation; LLS; Gabrielle's Angel Foundation for
Cancer Research; The Spastic Paralysis Foundation of the Illinois;
Eastern Iowa Branch of Kiwanis International; The Fidelity Foundation;
The University of Chicago Committee on Cancer Biology (CCB) Fellowship
Program; NIH/NCCAM [P01AT004418]; National Human Genome Research
Institute, NIH; The Deutsche Jose Carreras Leukamie Stiftung (DJCLS) [R
06/41v]; The Deutsche Forschungsgemeinschaft (DFG) Heisenberg-Stipendium
[BU 1339/3-1]
FX This work was supported in part by the Leukemia & Lymphoma Society (L.
L. S.) Translational Research Grant (J.D.R. and J.C.), the National
Institutes of Health (NIH) R01 grant CA127277 (J.C.), American Cancer
Society (ACS) Research Scholar grant (J.C.), the G. Harold and Leila Y.
Mathers Charitable Foundation (J.C.), LLS Special Fellowship (Z.L.),
Gabrielle's Angel Foundation for Cancer Research (J.C., Z.L., H. H., and
X.J.), The Spastic Paralysis Foundation of the Illinois, Eastern Iowa
Branch of Kiwanis International (J.D.R.), The Fidelity Foundation
(J.D.R. and J.C.), The University of Chicago Committee on Cancer Biology
(CCB) Fellowship Program (X.J.), NIH/NCCAM P01AT004418 (C. S. Y.), The
Intramural Research Program of National Human Genome Research Institute,
NIH (A. E. and P. P. L.), The Deutsche Jose Carreras Leukamie Stiftung
(DJCLS) grant R 06/41v (L. B.), and The Deutsche Forschungsgemeinschaft
(DFG) Heisenberg-Stipendium BU 1339/3-1 (L.B).
NR 48
TC 35
Z9 36
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 FEB 21
PY 2013
VL 121
IS 8
BP 1422
EP 1431
DI 10.1182/blood-2012-07-442004
PG 10
WC Hematology
SC Hematology
GA 182NK
UT WOS:000321750000027
PM 23264595
ER
PT J
AU Astermark, J
Donfield, SM
Gomperts, ED
Schwarz, J
Menius, ED
Pavlova, A
Oldenburg, J
Kessing, B
DiMichele, DM
Shapiro, AD
Winkler, CA
Berntorp, E
AF Astermark, Jan
Donfield, Sharyne M.
Gomperts, Edward D.
Schwarz, John
Menius, Erika D.
Pavlova, Anna
Oldenburg, Johannes
Kessing, Bailey
DiMichele, Donna M.
Shapiro, Amy D.
Winkler, Cheryl A.
Berntorp, Erik
CA Hemophilia Inhibitor Genetics
TI The polygenic nature of inhibitors in hemophilia A: results from the
Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort
SO BLOOD
LA English
DT Article
ID MALMO INTERNATIONAL BROTHER; GENOME-WIDE ASSOCIATION; FACTOR-VIII;
INFLAMMATORY DISEASES; AUTOIMMUNE-DISEASE; CELL-ACTIVATION;
RISK-FACTORS; FACTOR-XIII; POLYMORPHISMS; KINASES
AB Studies of determinants of development of inhibitory Abs to factor VIII in people with hemophilia A indicate a complex process involving multiple factors. The Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort was formed to extend our understanding of the genetic background of risk. The study group contains 833 subjects from 3 independent cohorts: brother pairs and singletons with and without a history of inhibitors, as well as 104 brother pairs discordant for inhibitor status. Using an Illumina iSelect platform, 13 331 single-nucleotide polymorphisms from 1081 genes, primarily immune response and immune modifier genes, were typed. Each cohort was analyzed separately with results combined using a meta-analytic technique. After adjustment for potential confounders, 53 single-nucleotide polymorphisms were found to be significant predictors of inhibitor status using the criteria of odds ratios in the same direction in all cohorts or allowing for a 20% interval around an odds ratio = 1 in 1 of the 3 and significant in at least 2. Of the 53 markers, 13 had meta P < .001. Eight of the 53 were significant predictors among the discordant pairs. Results support the complexity of the immune response and encourage further research with the goal of understanding the pathways involved. (Blood. 2013;121(8):1446-1454)
C1 [Astermark, Jan; Berntorp, Erik] Lund Univ, Ctr Thrombosis & Haemostasis, Skane Univ Hosp, SE-20502 Malmo, Sweden.
[Donfield, Sharyne M.; Schwarz, John; Menius, Erika D.] Rho Inc, Dept Biostat, Chapel Hill, NC USA.
[Gomperts, Edward D.] Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA.
[Pavlova, Anna; Oldenburg, Johannes] Univ Clin, Inst Expt Haematol & Transfus Med, Bonn, Germany.
[Kessing, Bailey; Winkler, Cheryl A.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[DiMichele, Donna M.] Weill Cornell Med Coll, Dept Pediat, New York, NY USA.
[Shapiro, Amy D.] Indiana Hemophilia & Thrombosis Ctr, Indianapolis, IN USA.
RP Astermark, J (reprint author), Lund Univ, Ctr Thrombosis & Haemostasis, Skane Univ Hosp, SE-20502 Malmo, Sweden.
EM jan.astermark@med.lu.se
FU Baxter BioScience; Frederick National Laboratory for Cancer Research,
National Institutes of Health (NIH) [HHSN261200800001E]; NIH, National
Cancer Institute, Center for Cancer Research; Wyeth; Research Fund at
Malmo University Hospital; NIH, National Institute of Child Health and
Human Development [R01-HD-41224]
FX This work was supported by an investigator-initiated grant from Baxter
BioScience and by federal funds from the Frederick National Laboratory
for Cancer Research, National Institutes of Health (NIH; contract number
HHSN261200800001E). This research was supported in part by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. The Malmo International Brother Study is
funded through grants from Wyeth and the Research Fund at Malmo
University Hospital. The Hemophilia Growth and Development Study is
funded by the NIH, National Institute of Child Health and Human
Development (grant R01-HD-41224).
NR 51
TC 46
Z9 46
U1 1
U2 10
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 FEB 21
PY 2013
VL 121
IS 8
BP 1446
EP 1454
DI 10.1182/blood-2012-06-434803
PG 9
WC Hematology
SC Hematology
GA 182NK
UT WOS:000321750000030
PM 23223434
ER
PT J
AU Cohen, KS
Cheng, S
Larson, MG
Cupples, LA
McCabe, EL
Wang, YA
Ngwa, JS
Martin, RP
Klein, RJ
Hashmi, B
Ge, Y
O'Donnell, CJ
Vasan, RS
Shaw, SY
Wang, TJ
AF Cohen, Kenneth S.
Cheng, Susan
Larson, Martin G.
Cupples, L. Adrienne
McCabe, Elizabeth L.
Wang, Ying A.
Ngwa, Julius S.
Martin, Roderick P.
Klein, Rachael J.
Hashmi, Basma
Ge, Yin
O'Donnell, Christopher J.
Vasan, Ramachandran S.
Shaw, Stanley Y.
Wang, Thomas J.
TI Circulating CD34(+) progenitor cell frequency is associated with
clinical and genetic factors
SO BLOOD
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; ACUTE MYOCARDIAL-INFARCTION; GENOME-WIDE
ASSOCIATION; CARDIOVASCULAR RISK; ENDOTHELIAL-CELLS; STATIN THERAPY;
HEART-DISEASE; DYSFUNCTION; MOBILIZATION; POPULATION
AB Circulating blood CD34(+) cells consist of hematopoietic stem/progenitor cells, angiogenic cells, and endothelial cells. In addition to their clinical use in hematopoietic stem cell transplantation, CD34(+) cells may also promote therapeutic neovascularization. Therefore, understanding the factors that influence circulating CD34(+) cell frequency has wide implications for vascular biology in addition to stem cell transplantation. In the present study, we examined the clinical and genetic characteristics associated with circulating CD34(+) cell frequency in a large, community-based sample of 1786 Framingham Heart Study participants. Among subjects without cardiovascular disease (n = 1595), CD34(+) frequency was inversely related to older age, female sex, and smoking. CD34(+) frequency was positively related to weight, serum total cholesterol, and statin therapy. Clinical covariates accounted for 6.3% of CD34(+) variability. CD34(+) frequency was highly heritable (h(2) = 54%; P < .0001). Genome-wide association analysis of CD34(+) frequency identified suggestive associations at several loci, including OR4C12 (chromosome 11; P = 6.7 x 10(-7)) and ENO1 and RERE (chromosome 1; P = 8.8 x 10(-7)). CD34(+) cell frequency is reduced in older subjects and is influenced by environmental factors including smoking and statin use. CD34(+) frequency is highly heritable. The results of the present study have implications for therapies that use CD34+ cell populations and support efforts to better understand the genetic mechanisms that underlie CD34(+) frequency.
C1 [Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Cohen, Kenneth S.; Martin, Roderick P.; Klein, Rachael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA.
[Cohen, Kenneth S.] Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA.
[Cheng, Susan; McCabe, Elizabeth L.; O'Donnell, Christopher J.; Shaw, Stanley Y.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Cheng, Susan; Larson, Martin G.; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA 90034 USA.
[Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Cupples, L. Adrienne; Wang, Ying A.; Ngwa, Julius S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Martin, Roderick P.] Genzyme Corp, Cambridge, MA USA.
[Hashmi, Basma] Harvard Univ, Dept Bioengn, Boston, MA 02115 USA.
[Ge, Yin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA.
[O'Donnell, Christopher J.] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Div Cardiol, Boston, MA 02118 USA.
[Shaw, Stanley Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA.
RP Wang, TJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA.
EM kcohen@medicine.bsd.uchicago.edu; shaw.stanley@mgh.harvard.edu;
tjwang@partners.org
OI Larson, Martin/0000-0002-9631-1254; Cupples, L.
Adrienne/0000-0003-0273-7965
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195, R01-HL083197, R01-HL93328]; National Institutes of Health
[K99HL107642]; Ellison Foundation
FX This work was supported in part by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (contract number N01-HC-25195, grant
R01-HL083197 to T.J.W., and grant R01-HL93328 to R. S. V.). S. C. is
supported in part by National Institutes of Health grant K99HL107642 and
the Ellison Foundation.
NR 47
TC 23
Z9 23
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD FEB 21
PY 2013
VL 121
IS 8
BP E50
EP E56
DI 10.1182/blood-2012-05-424846
PG 7
WC Hematology
SC Hematology
GA 182NK
UT WOS:000321750000002
PM 23287867
ER
PT J
AU Mendonca, VRR
Queiroz, ATL
Lopes, FM
Andrade, BB
Barral-Netto, M
AF Mendonca, Vitor R. R.
Queiroz, Artur T. L.
Lopes, Fabricio M.
Andrade, Bruno B.
Barral-Netto, Manoel
TI Networking the host immune response in Plasmodium vivax malaria
SO MALARIA JOURNAL
LA English
DT Article
DE Malaria; Plasmodium vivax; Biomarkers; Network analysis
ID CD4(+) T-CELLS; FALCIPARUM-MALARIA; BRAZILIAN AMAZON; CEREBRAL MALARIA;
LIVER STAGES; CHILDREN; SUSCEPTIBILITY; SEVERITY; INTERLEUKIN-10;
CHEMOKINES
AB Background: Plasmodium vivax malaria clinical outcomes are a consequence of the interaction of multiple parasite, environmental and host factors. The host molecular and genetic determinants driving susceptibility to disease severity in this infection are largely unknown. Here, a network analysis of large-scale data from a significant number of individuals with different clinical presentations of P. vivax malaria was performed in an attempt to identify patterns of association between various candidate biomarkers and the clinical outcomes.
Methods: A retrospective analysis of 530 individuals from the Brazilian Amazon, including P. vivax-infected individuals who developed different clinical outcomes (148 asymptomatic malaria, 187 symptomatic malaria, 13 severe non-lethal malaria, and six severe lethal malaria) as well as 176 non-infected controls, was performed. Plasma levels of liver transaminases, bilirubins, creatinine, fibrinogen, C-reactive protein, superoxide dismutase (SOD)-1, haem oxygenase (HO)-1 and a panel composed by multiple cytokines and chemokines were measured and compared between the different clinical groups using network analysis.
Results: Non-infected individuals displayed several statistically significant interactions in the networks, including associations between the levels of IL-10 and IL-4 with the chemokine CXCL9. Individuals with asymptomatic malaria displayed multiple significant interactions involving IL-4. Subjects with mild or severe non-lethal malaria displayed substantial loss of interactions in the networks and TNF had significant associations more frequently with other parameters. Cases of lethal P. vivax malaria infection were associated with significant interactions between TNF ALT, HO-1 and SOD-1.
Conclusions: The findings imply that clinical immunity to P. vivax malaria is associated with multiple significant interactions in the network, mostly involving IL-4, while lethality is linked to a systematic reduction of complexity of these interactions and to an increase in connections between markers linked to haemolysis-induced damage.
C1 [Mendonca, Vitor R. R.; Queiroz, Artur T. L.; Barral-Netto, Manoel] Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil.
[Mendonca, Vitor R. R.; Barral-Netto, Manoel] Univ Fed Bahia, Fac Med, Salvador, BA, Brazil.
[Lopes, Fabricio M.] Univ Sao Paulo, Inst Matemat & Estat, Sao Paulo, Brazil.
[Lopes, Fabricio M.] Univ Tecnol Fed Parana, Cornelio Procopio, Brazil.
[Andrade, Bruno B.] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20893 USA.
[Barral-Netto, Manoel] Inst Nacl Ciencia & Tecnol, Inst Invest Imunol, Sao Paulo, Brazil.
RP Andrade, BB (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20893 USA.
EM andradebd@niaid.nih.gov
RI Barral Netto, Manoel/B-3904-2009; Andrade, Bruno/J-9111-2012; Queiroz,
Artur/F-6083-2014; Lopes, Fabricio/F-6996-2010
OI Barral Netto, Manoel/0000-0002-5823-7903; Andrade,
Bruno/0000-0001-6833-3811; Lopes, Fabricio/0000-0002-8786-3313
FU FINEP/FNDCT-CT Amazonia [010409605]; FIOCRUZ; CNPq; National Institute
of Allergy and Infectious Diseases, National Institute of Health
FX The authors thank David Kugler (NIAID, NIH, USA) for critical help with
the data analysis and helpful discussions. A special thank to Joao
Gambati (FUNASA, Brazil), Luis Marcelo Camargo (USP, Brazil) and the
study team at FIOCRUZ-Bahia, Brazil, Daniela Andrade, Nivea Luz, Jorge
Tolentino, Adorielze Leite, and Drs Aldina Barral and Jorge Clarencio
for help in logistics of the field study and experiments involving
cytokine measurements. This work was supported by FINEP/FNDCT-CT
Amazonia [field work; grant # 010409605] and by FIOCRUZ. MB-N is a
senior investigator from CNPq. VRRM is supported by CNPq. The work of
BBA is supported by the intramural research programme of the National
Institute of Allergy and Infectious Diseases, National Institute of
Health. The funders had no role in the study design, data collection and
analysis, decision to publish or preparation of the manuscript.
NR 41
TC 21
Z9 22
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD FEB 21
PY 2013
VL 12
AR 69
DI 10.1186/1475-2875-12-69
PG 10
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 119AM
UT WOS:000317068900001
PM 23433077
ER
PT J
AU Jankovic, M
Feldhahn, N
Oliveira, TY
Silva, IT
Kieffer-Kwon, KR
Yamane, A
Resch, W
Klein, I
Robbiani, DF
Casellas, R
Nussenzweig, MC
AF Jankovic, Mila
Feldhahn, Niklas
Oliveira, Thiago Y.
Silva, Israel T.
Kieffer-Kwon, Kyong-Rim
Yamane, Arito
Resch, Wolfgang
Klein, Isaac
Robbiani, Davide F.
Casellas, Rafael
Nussenzweig, Michel C.
TI 53BP1 Alters the Landscape of DNA Rearrangements and Suppresses
AID-Induced B Cell Lymphoma
SO MOLECULAR CELL
LA English
DT Article
ID INDUCED CYTIDINE DEAMINASE; CLASS SWITCH RECOMBINATION; DOUBLE-STRAND
BREAKS; CHROMOSOMAL TRANSLOCATIONS; SOMATIC HYPERMUTATION; GENOMIC
INSTABILITY; SEQUENCING REVEALS; TUMOR-SUPPRESSOR; C-MYC; DAMAGE
AB Deficiencies in factors that regulate the DNA damage response enhance the incidence of malignancy by destabilizing the genome. However, the precise influence of the DNA damage response on regulation of cancer-associated rearrangements is not well defined. Here we examine the genome-wide impact of tumor protein P53-binding protein 1 (53BP1) deficiency in lymphoma and translocation. While both activation-induced cytidine deaminase (AID) and 53BP1 have been associated with cancer in humans, neither AID overexpression nor loss of 53BP1 is sufficient to produce malignancy. However, the combination of 53BP1 deficiency and AID deregulation results in B cell lymphoma. Deep sequencing of the genome of 53BP1(-/-) cancer cells and translocation capture sequencing (TC-Seq) of primary 53BP1(-/-) B cells revealed that their chromosomal rearrangements differ from those found in wildtype cells in that they show increased DNA end resection. Moreover, loss of 53BP1 alters the trans-locatome by increasing rearrangements to intergenic regions.
C1 [Jankovic, Mila; Feldhahn, Niklas; Oliveira, Thiago Y.; Silva, Israel T.; Klein, Isaac; Robbiani, Davide F.; 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.
[Kieffer-Kwon, Kyong-Rim; Yamane, Arito; Resch, Wolfgang; Casellas, Rafael] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Oliveira, Thiago Y.] Med Sch Ribeirao Preto USP, Dept Genet, BR-14051140 Sao Paulo, Brazil.
[Oliveira, Thiago Y.; Silva, Israel T.] Natl Inst Sci & Technol Stem Cells & Cell Therapy, BR-14051140 Sao Paulo, Brazil.
RP Casellas, R (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA.
EM casellar@mail.nih.gov; nussen@rockefeller.edu
RI Yamane, Arito/A-2959-2013; Silva, Israel/N-3858-2014;
OI Silva, Israel/0000-0002-4687-1499; Oliveira, Thiago/0000-0002-2654-0879
FU NIH [AI037526]
FX We thank all members of the Nussenzweig laboratory for discussions. We
thank Dr F. Alt for helpful suggestions and discussions. We thank Klara
Velinzon and Yelena Shatalina for cell sorting, and Thomas Eisenreich
and David Bosque for help with mice. The work was supported by a NIH
grant to M.C.N., number AI037526. N.F. was a Fellow of the Leukemia and
Lymphoma Society. M.C.N. is a Howard Hughes Medical Institute
Investigator.
NR 61
TC 17
Z9 18
U1 2
U2 11
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 FEB 21
PY 2013
VL 49
IS 4
BP 623
EP 631
DI 10.1016/j.molcel.2012.11.029
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 098NE
UT WOS:000315555200007
PM 23290917
ER
PT J
AU Freeman, AK
Ritt, DA
Morrison, DK
AF Freeman, Alyson K.
Ritt, Daniel A.
Morrison, Deborah K.
TI Effects of Raf Dimerization and Its Inhibition on Normal and
Disease-Associated Raf Signaling
SO MOLECULAR CELL
LA English
DT Article
ID FACIO-CUTANEOUS SYNDROME; B-RAF; ONCOGENIC RAS; MAPK PATHWAY; WILD-TYPE;
A-RAF; BRAF; HETERODIMERIZATION; RESISTANCE; ACTIVATION
AB Raf kinases are essential for normal Ras-Raf-MEK-ERK pathway signaling, and activating mutations in components of this pathway are associated with a variety of human cancers, as well as the related developmental disorders Noonan, LEOPARD, and cardiofaciocutaneous syndromes. Although the Raf kinases are known to dimerize during normal and disease-associated Raf signaling, the functional significance of Raf dimerization has not been fully elucidated. Here, using mutational analysis and a peptide inhibitor, we show that dimerization is required for normal Ras-dependent Raf activation and for the biological function of disease-associated Raf mutants with moderate, low, or impaired kinase activity. However, dimerization is not needed for the function of B-Raf mutants with high catalytic activity, such as V600E-B-Raf. Importantly, we find that a dimer interface peptide can effectively block Raf dimerization and inhibit Raf signaling when dimerization is required for Raf function, thus identifying the Raf dimer interface as a therapeutic target.
C1 [Freeman, Alyson K.; Ritt, Daniel A.; Morrison, Deborah K.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
RP Morrison, DK (reprint author), NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
EM morrisod@mail.nih.gov
FU National Cancer Institute
FX We would like to thank Dr. Ming Zhou at SAIC-Frederick for assistance
with the mass spectrometry analysis. This project was funded by federal
funds from the National Cancer Institute.
NR 22
TC 61
Z9 62
U1 0
U2 16
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 FEB 21
PY 2013
VL 49
IS 4
BP 751
EP 758
DI 10.1016/j.molcel.2012.12.018
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 098NE
UT WOS:000315555200018
PM 23352452
ER
PT J
AU Modjarrad, K
Mohraz, M
Madani, N
AF Modjarrad, Kayvon
Mohraz, Minoo
Madani, Navid
TI Iran needs global support to fight HIV
SO NATURE
LA English
DT Letter
C1 [Modjarrad, Kayvon] NIAID, Bethesda, MD 20892 USA.
[Mohraz, Minoo] Univ Tehran Med Sci, Tehran, Iran.
[Madani, Navid] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Modjarrad, K (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kayvon.modjarrad@nih.gov
NR 1
TC 1
Z9 1
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2013
VL 494
IS 7437
BP 314
EP 314
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900022
PM 23426315
ER
PT J
AU Burns, MB
Lackey, L
Carpenter, MA
Rathore, A
Land, AM
Leonard, B
Refsland, EW
Kotandeniya, D
Tretyakova, N
Nikas, JB
Yee, D
Temiz, NIA
Donohue, DE
McDougle, RM
Brown, WL
Law, EK
Harris, RS
AF Burns, Michael B.
Lackey, Lela
Carpenter, Michael A.
Rathore, Anurag
Land, Allison M.
Leonard, Brandon
Refsland, Eric W.
Kotandeniya, Delshanee
Tretyakova, Natalia
Nikas, Jason B.
Yee, Douglas
Temiz, Nuri I. A.
Donohue, Duncan E.
McDougle, Rebecca M.
Brown, William L.
Law, Emily K.
Harris, Reuben S.
TI APOBEC3B is an enzymatic source of mutation in breast cancer
SO NATURE
LA English
DT Article
ID SOMATIC HYPERMUTATION; CELL CARCINOMA; FOREIGN DNA; RESTRICTION;
LANDSCAPE; DEAMINATION; MECHANISMS; GENOMES; AID
AB Several mutations are required for cancer development, and genome sequencing has revealed that many cancers, including breast cancer, have somatic mutation spectra dominated by C-to-T transitions(1-9). Most of these mutations occur at hydrolytically disfavoured(10) non-methylated cytosines throughout the genome, and are sometimes clustered(8). Here we show that the DNA cytosine deaminase APOBEC3B is a probable source of these mutations. APOBEC3B messenger RNA is upregulated in most primary breast tumours and breast cancer cell lines. Tumours that express high levels of APOBEC3B have twice as many mutations as those that express low levels and are more likely to have mutations in TP53. Endogenous APOBEC3B protein is predominantly nuclear and the only detectable source of DNA C-to-U editing activity in breast cancer cell-line extracts. Knockdown experiments show that endogenous APOBEC3B correlates with increased levels of genomic uracil, increased mutation frequencies, and C-to-T transitions. Furthermore, induced APOBEC3B overexpression causes cell cycle deviations, cell death, DNA fragmentation, gamma-H2AX accumulation and C-to-T mutations. Our data suggest a model in which APOBEC3B-catalysed deamination provides a chronic source of DNA damage in breast cancers that could select TP53 inactivation and explain how some tumours evolve rapidly and manifest heterogeneity.
C1 [Burns, Michael B.; Lackey, Lela; Carpenter, Michael A.; Rathore, Anurag; Land, Allison M.; Refsland, Eric W.; McDougle, Rebecca M.; Brown, William L.; Law, Emily K.; Harris, Reuben S.] Univ Minnesota, Biochem Mol Biol & Biophys Dept, Minneapolis, MN 55455 USA.
[Burns, Michael B.; Lackey, Lela; Carpenter, Michael A.; Rathore, Anurag; Land, Allison M.; Leonard, Brandon; Refsland, Eric W.; Kotandeniya, Delshanee; Tretyakova, Natalia; Nikas, Jason B.; Yee, Douglas; McDougle, Rebecca M.; Brown, William L.; Law, Emily K.; Harris, Reuben S.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
[Burns, Michael B.; Lackey, Lela; Carpenter, Michael A.; Rathore, Anurag; Land, Allison M.; Leonard, Brandon; Refsland, Eric W.; McDougle, Rebecca M.; Brown, William L.; Law, Emily K.; Harris, Reuben S.] Univ Minnesota, Inst Mol Virol, Minneapolis, MN 55455 USA.
[Burns, Michael B.; Lackey, Lela; Carpenter, Michael A.; Rathore, Anurag; Land, Allison M.; Leonard, Brandon; Refsland, Eric W.; McDougle, Rebecca M.; Brown, William L.; Law, Emily K.; Harris, Reuben S.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA.
[Leonard, Brandon; Harris, Reuben S.] Univ Minnesota, Microbiol Canc Biol & Immunol Grad Program, Minneapolis, MN 55455 USA.
[Kotandeniya, Delshanee; Tretyakova, Natalia] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA.
[Temiz, Nuri I. A.; Donohue, Duncan E.] SAIC Frederick Inc, In Silico Res Ctr Excellence, Adv Biomed Comp Ctr, Informat Syst Program,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Harris, RS (reprint author), Univ Minnesota, Biochem Mol Biol & Biophys Dept, Minneapolis, MN 55455 USA.
EM rsh@umn.edu
OI Lackey, Lela/0000-0003-2163-4005; Burns, Michael/0000-0001-9791-4359
FU Academic Health Center; National Institutes of Health (NIH) [P30
CA77598, P50 CA101955, KL2 RR033182]; Cancer Biology Training Grant [NIH
NCI T32 CA009138]; Department of Defense Breast Cancer Research Program
Predoctoral Fellowship [BC101124]; National Science Foundation
Predoctoral Fellowship; Institute for Molecular Virology Training Grant
NIH [T32 AI083196]; NIH [F32 GM095219, F31 DA033186, R01 AI064046, NIH
P01 GM091743, 1UL1RR033183]; CIHR; National Cancer Institute, NIH,
CBIIT/caBIG ISRCE [09-260]; Children's Cancer Research Fund
FX We thank J. Hultquist and R. Vogel for statistics, T. Hwang for
bioinformatic assistance, V. Polunovsky for hTERT-HMECs, V. Simon for
shRNA, S. Kaufmann, C. Lange and D. Largaespada for consultation, and
the Masonic Cancer Center Breast Cancer Research Fund for purchasing the
ATCC breast cancer panel. Tissues were obtained from the Masonic Cancer
Center Tissue Procurement Facility, which is part of BioNet, supported
by the Academic Health Center and National Institutes of Health (NIH)
grants P30 CA77598 (D.Y.), P50 CA101955 (D. Buchsbaum) and KL2 RR033182
(B. Blazar). M.B.B. was supported in part by a Cancer Biology Training
Grant (NIH NCI T32 CA009138) and a Department of Defense Breast Cancer
Research Program Predoctoral Fellowship (BC101124). L.L. was supported
in part by a National Science Foundation Predoctoral Fellowship and by a
position on the Institute for Molecular Virology Training Grant NIH T32
AI083196. MAC. was supported by an NIH postdoctoral fellowship (F32
GM095219). A.M.L. was supported by a CIHR postdoctoral fellowship.
E.W.R. was supported by a position on the Institute for Molecular
Virology Training Grant NIH T32 AI083196 and subsequently by an NIH
predoctoral fellowship (F31 DA033186). Computational analyses (N.A.T.
and D.E.D.) were supported by federal funds from the National Cancer
Institute, NIH, CBIIT/caBIG ISRCE yellow task 09-260. The Harris
laboratory was supported in part by NIH R01 AI064046, NIH P01 GM091743,
the Children's Cancer Research Fund, and a seed grant from the
University of Minnesota Clinical and Translational Science Institute
(supported by NIH 1UL1RR033183).
NR 27
TC 235
Z9 238
U1 4
U2 64
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2013
VL 494
IS 7437
BP 366
EP 370
DI 10.1038/nature11881
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900041
PM 23389445
ER
PT J
AU Rappaport, SM
Berezhkovskii, AM
Zimmerberg, J
Bezrukov, SM
AF Rappaport, Shay M.
Berezhkovskii, Alexander M.
Zimmerberg, Joshua
Bezrukov, Sergey M.
TI Thermodynamics of interleaflet cavitation in lipid bilayer membranes
SO PHYSICAL REVIEW E
LA English
DT Article
ID ELASTIC PROPERTIES; DRUG-DELIVERY; ULTRASOUND; LIPOSOMES; RELEASE
AB Interleaflet cavitation in lipid bilayer membranes, or, shortly, intramembrane cavitation (IMC), is the formation of gas bubbles between the two leaflets of the membrane. The present paper focuses on the thermodynamics of IMC, namely, on the minimum work required to form an intramembrane cavity. The minimum work can be separated into two parts, one that depends on the volume and number of gas molecules in the bubble and another that depends on the bubble geometry. Minimization of the second part at a fixed bubble volume determines the optimized bubble shape. In homogeneous cavitation this part is proportional to the bubble surface area and therefore the bubble is spherical. In contrast, in IMC the second part is no longer a simple function of the bubble area and the optimized cavity is not spherical because of the finite elasticity of the membrane. Using a simplified assumption about the cavity shape, the geometry-dependent term is derived and minimized at a fixed cavity volume. It is found that the optimized cavity is almost spherical at large bubble volumes, while at small volumes the cavity has a lenslike shape. The optimized shape is used to analyze the minimum work of IMC. DOI: 10.1103/PhysRevE.87.022715
C1 [Rappaport, Shay M.; Berezhkovskii, Alexander M.; Zimmerberg, Joshua; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Rappaport, Shay M.; Zimmerberg, Joshua; Bezrukov, Sergey M.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Rappaport, SM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
FU Department of Defense through the Center for Neuroscience and
Regenerative Medicine; Intramural Research Program of the NIH, Center
for Information Technology; Eunice Kennedy Shriver National Institute of
Child Health and Human Development
FX We are grateful to Valdimir Zitserman for helpful and illuminating
discussions. This study was supported by the Department of Defense
through the Center for Neuroscience and Regenerative Medicine and the
Intramural Research Program of the NIH, Center for Information
Technology, and Eunice Kennedy Shriver National Institute of Child
Health and Human Development.
NR 19
TC 1
Z9 1
U1 0
U2 16
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 1539-3755
J9 PHYS REV E
JI Phys. Rev. E
PD FEB 21
PY 2013
VL 87
IS 2
AR 022715
DI 10.1103/PhysRevE.87.022715
PG 8
WC Physics, Fluids & Plasmas; Physics, Mathematical
SC Physics
GA 094RY
UT WOS:000315282700009
PM 23496556
ER
PT J
AU Mertins, SD
Scudiero, DA
Hollingshead, MG
Divelbiss, RD
Alley, MC
Monks, A
Covell, DG
Hite, KM
Salomon, DS
Niederhuber, JE
AF Mertins, Susan D.
Scudiero, Dominic A.
Hollingshead, Melinda G.
Divelbiss, Raymond D., Jr.
Alley, Michael C.
Monks, Anne
Covell, David G.
Hite, Karen M.
Salomon, David S.
Niederhuber, John E.
TI A Small Molecule (Pluripotin) as a Tool for Studying Cancer Stem Cell
Biology: Proof of Concept
SO PLOS ONE
LA English
DT Article
ID STEM/PROGENITOR CELLS; PROSPECTIVE IDENTIFICATION; GENE-EXPRESSION;
TUMOR; DIFFERENTIATION; PROLIFERATION; INHIBITORS; CARCINOMA; REVEALS;
PATHWAY
AB Background: Cancer stem cells (CSC) are thought to be responsible for tumor maintenance and heterogeneity. Bona fide CSC purified from tumor biopsies are limited in supply and this hampers study of CSC biology. Furthermore, purified stem-like CSC subpopulations from existing tumor lines are unstable in culture. Finding a means to overcome these technical challenges would be a useful goal. In a first effort towards this, we examined whether a chemical probe that promotes survival of murine embryonic stem cells without added exogenous factors can alter functional characteristics in extant tumor lines in a fashion consistent with a CSC phenotype.
Methodology/Principal Findings: The seven tumor lines of the NCI60 colon subpanel were exposed to SC-1 (pluripotin), a dual kinase and GTPase inhibitor that promotes self-renewal, and then examined for tumorigenicity under limiting dilution conditions and clonogenic activity in soft agar. A statistically significant increase in tumor formation following SC-1 treatment was observed (p<0.04). Cloning efficiencies and expression of putative CSC surface antigens (CD133 and CD44) were also increased. SC-1 treatment led to sphere formation in some colon tumor lines. Finally, SC-1 inhibited in vitro kinase activity of RSK2, and another RSK2 inhibitor increased colony formation implicating a role for this kinase in eliciting a CSC phenotype.
Conclusions/Significance: These findings validate a proof of concept study exposure of extant tumor lines to a small molecule may provide a tractable in vitro model for understanding CSC biology.
C1 [Mertins, Susan D.; Alley, Michael C.; Covell, David G.] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21701 USA.
[Scudiero, Dominic A.; Monks, Anne; Hite, Karen M.] NCI, SAIC Frederick, Frederick, MD 21701 USA.
[Hollingshead, Melinda G.; Divelbiss, Raymond D., Jr.] NCI, Biol Testing Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21701 USA.
[Salomon, David S.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Niederhuber, John E.] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Mertins, SD (reprint author), NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21701 USA.
EM smertins@mail.nih.gov
FU Division for Cancer Diagnosis and Treatment; Center for Cancer Research
at the National Cancer Institute; NCI Contract [HHSN261200800001E]
FX This study was supported by the Division for Cancer Diagnosis and
Treatment and Center for Cancer Research at the National Cancer
Institute and partially funded by NCI Contract HHSN261200800001E. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 42
TC 2
Z9 2
U1 0
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 21
PY 2013
VL 8
IS 2
AR e57099
DI 10.1371/journal.pone.0057099
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 093IT
UT WOS:000315186000076
PM 23437320
ER
PT J
AU Tammemagi, MC
Katki, HA
Hocking, WG
Church, TR
Caporaso, N
Kvale, PA
Chaturvedi, AK
Silvestri, GA
Riley, TL
Commins, J
Berg, CD
AF Tammemaegi, Martin C.
Katki, Hormuzd A.
Hocking, William G.
Church, Timothy R.
Caporaso, Neil
Kvale, Paul A.
Chaturvedi, Anil K.
Silvestri, Gerard A.
Riley, Tom L.
Commins, John
Berg, Christine D.
TI Selection Criteria for Lung-Cancer Screening
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID RISK PREDICTION MODEL; RANDOMIZED PROSTATE; INCREMENTAL VALUE; CHEST
RADIOGRAPH; TRIAL; VALIDATION; MORTALITY; SMOKERS
AB BACKGROUND
The National Lung Screening Trial (NLST) used risk factors for lung cancer (e. g., >= 30 pack-years of smoking and <15 years since quitting) as selection criteria for lung-cancer screening. Use of an accurate model that incorporates additional risk factors to select persons for screening may identify more persons who have lung cancer or in whom lung cancer will develop.
METHODS
We modified the 2011 lung-cancer risk-prediction model from our Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to ensure applicability to NLST data; risk was the probability of a diagnosis of lung cancer during the 6-year study period. We developed and validated the model (PLCOM2012) with data from the 80,375 persons in the PLCO control and intervention groups who had ever smoked. Discrimination (area under the receiver-operating-characteristic curve [AUC]) and calibration were assessed. In the validation data set, 14,144 of 37,332 persons (37.9%) met NLST criteria. For comparison, 14,144 highest-risk persons were considered positive (eligible for screening) according to PLCOM2012 criteria. We compared the accuracy of PLCOM2012 criteria with NLST criteria to detect lung cancer. Cox models were used to evaluate whether the reduction in mortality among 53,202 persons undergoing low-dose computed tomographic screening in the NLST differed according to risk.
RESULTS
The AUC was 0.803 in the development data set and 0.797 in the validation data set. As compared with NLST criteria, PLCOM2012 criteria had improved sensitivity (83.0% vs. 71.1%, P<0.001) and positive predictive value (4.0% vs. 3.4%, P = 0.01), without loss of specificity (62.9% and. 62.7%, respectively; P = 0.54); 41.3% fewer lung cancers were missed. The NLST screening effect did not vary according to PLCOM2012 risk (P = 0.61 for interaction).
CONCLUSIONS
The use of the PLCOM2012 model was more sensitive than the NLST criteria for lung-cancer detection.
C1 [Tammemaegi, Martin C.] Brock Univ, Dept Community Hlth Sci, St Catharines, ON L2S 3A1, Canada.
[Katki, Hormuzd A.; Caporaso, Neil; Chaturvedi, Anil K.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Berg, Christine D.] NCI, Early Detect Res Grp, Canc Prevent Div, NIH, Rockville, MD USA.
[Riley, Tom L.; Commins, John] Informat Management Serv Inc, Rockville, MD USA.
[Hocking, William G.] Marshfield Clin Res Fdn, Marshfield, WI USA.
[Church, Timothy R.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[Kvale, Paul A.] Henry Ford Hlth Syst, Detroit, MI USA.
[Silvestri, Gerard A.] Med Univ S Carolina, Charleston, SC USA.
RP Tammemagi, MC (reprint author), Brock Univ, Dept Community Hlth Sci, Walker Complex S,Rm 306,500 Glenridge Ave, St Catharines, ON L2S 3A1, Canada.
EM martin.tammemagi@brocku.ca
RI Berg , Christine/K-1047-2014; Katki, Hormuzd/B-4003-2015; Chaturvedi,
Anil/J-2024-2015;
OI Chaturvedi, Anil/0000-0003-2696-8899; Hocking,
William/0000-0002-0690-3759; Church, Timothy R./0000-0003-3292-5035
FU National Cancer Institute (NCI); Division of Cancer Prevention;
Intramural Research Program of the Division of Cancer Epidemiology and
Genetics; Cancer Imaging Program, Division of Cancer Treatment and
Diagnosis [U01-CA-80098, U01-CA-79778]
FX The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening
Trial was supported by the National Cancer Institute (NCI), in part by
contracts with the Division of Cancer Prevention and by the Intramural
Research Program of the Division of Cancer Epidemiology and Genetics.
The American College of Radiology Imaging Network component of the
National Lung Screening Trial (NLST) was supported by grants provided
under a cooperative agreement with the Cancer Imaging Program, Division
of Cancer Treatment and Diagnosis (U01-CA-80098 and U01-CA-79778). The
Lung Screening Study sites of the NLST were supported by contracts with
the Early Detection Research Group and Biometry Research Group, Division
of Cancer Prevention (N01-CN-25514, to the University of
Colorado-Denver; N01-CN-25522, to Georgetown University; N01-CN-25515,
to the Pacific Health Research and Education Institute; N01-CN-25512, to
the Henry Ford Health System; N01-CN-25513, to the University of
Minnesota; N01-CN-25516, to Washington University in St. Louis;
N01-CN-25511, to the University of Pittsburgh; N01-CN-25524, to the
University of Utah; N01-CN-25518, to the Marshfield Clinic Research
Foundation; N01-CN-75022, to the University of Alabama at Birmingham;
N01-CN-25476, to Westat; and N02-CN-63300, to Information Management
Services).
NR 28
TC 154
Z9 166
U1 2
U2 30
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 FEB 21
PY 2013
VL 368
IS 8
BP 728
EP 736
DI 10.1056/NEJMoa1211776
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 092CG
UT WOS:000315095800007
PM 23425165
ER
PT J
AU Zumla, A
Raviglione, M
Hafner, R
von Reyn, CF
AF Zumla, Alimuddin
Raviglione, Mario
Hafner, Richard
von Reyn, C. Fordham
TI CURRENT CONCEPTS Tuberculosis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID MULTIDRUG-RESISTANT TUBERCULOSIS; HIV-INFECTED ADULTS; ANTIRETROVIRAL
THERAPY; PULMONARY TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; ACTIVE
TUBERCULOSIS; UNITED-STATES; TRIAL; PREVENTION; DIAGNOSIS
C1 [Zumla, Alimuddin] UCL, Sch Med, Dept Infect, Div Infect & Immun, London W1N 8AA, England.
[Raviglione, Mario] WHO, STOP TB Dept, Geneva, Switzerland.
[Hafner, Richard] NIAID, TB Clin Res Branch, Div Aids, NIH, Bethesda, MD 20892 USA.
[von Reyn, C. Fordham] Geisel Sch Med Dartmouth, Sect Infect Dis & Int Hlth, Hanover, NH USA.
RP Zumla, A (reprint author), Ctr Clin Microbiol, Div Infect & Immun, 2nd Fl,UCL Royal Free Campus,Rowland Hill St, London NW3 OPE, England.
EM a.zumla@ucl.ac.uk
RI Rivet, Catherine/M-7978-2014;
OI Zumla, Alimuddin/0000-0002-5111-5735
FU Oxford Immunotec
FX Dr. von Reyn reports receiving consulting fees from Oxford Immunotec. No
other potential conflict of interest relevant to this article was
reported.
NR 71
TC 259
Z9 273
U1 7
U2 105
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 FEB 21
PY 2013
VL 368
IS 8
BP 745
EP 755
DI 10.1056/NEJMra1200894
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 092CG
UT WOS:000315095800009
PM 23425167
ER
PT J
AU Murphy, MP
Siegel, RM
AF Murphy, Michael P.
Siegel, Richard M.
TI Mitochondrial ROS Fire Up T Cell Activation
SO IMMUNITY
LA English
DT Editorial Material
ID SIGNAL-TRANSDUCTION
AB Metabolic reprogramming has emerged as an important feature of immune cell activation. Two new studies, including Sena et al. (2013) in this issue of Immunity, identify mitochondrial reactive oxygen species (ROS) arising from metabolic reprogramming as signaling molecules in T cell activation.
C1 [Murphy, Michael P.] MRC, Mitochondrial Biol Unit, Cambridge CB2 0XY, England.
[Siegel, Richard M.] NIAMSD, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
RP Siegel, RM (reprint author), NIAMSD, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
EM rsiegel@nih.gov
RI Murphy, Michael/C-2120-2009
OI Murphy, Michael/0000-0003-1115-9618
NR 9
TC 12
Z9 14
U1 1
U2 4
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 FEB 21
PY 2013
VL 38
IS 2
BP 201
EP 202
DI 10.1016/j.immuni.2013.02.005
PG 2
WC Immunology
SC Immunology
GA AA2RC
UT WOS:000330940800001
PM 23438817
ER
PT J
AU Mandl, JN
Monteiro, JP
Vrisekoop, N
Germain, RN
AF Mandl, Judith N.
Monteiro, Joao P.
Vrisekoop, Nienke
Germain, Ronald N.
TI T Cell-Positive Selection Uses Self-Ligand Binding Strength to Optimize
Repertoire Recognition of Foreign Antigens
SO IMMUNITY
LA English
DT Article
ID MAJOR HISTOCOMPATIBILITY COMPLEX; MHC CLASS-II; SENSORY ADAPTATION;
NAIVE CD4(+); RECEPTOR; PEPTIDE; TCR; SPECIFICITY; AFFINITY; AVIDITY
AB Developing T cells express diverse antigen receptors whose specificities are not prematched to the foreign antigens they eventually encounter. Past experiments have revealed that thymocytes must productively signal in response to self antigens to mature and enter the peripheral T cell pool (positive selection), but how this process enhances effective mature T cell responses to foreign antigen is not fully understood. Here we have documented an unsuspected connection between thymic recognition events and foreign antigen-driven T cell responses. We find that the strength of self-reactivity is a clone-specific property unexpectedly directly related to the strength of T cell receptor (TCR) binding to presented foreign antigen. T cells with receptors showing stronger interaction with self dominate in responses to infections and accumulate in aging individuals, revealing that positive selection contributes to effective immunity by skewing the mature TCR repertoire toward highly effective recognition of pathogens that pose a danger to the host.
C1 [Mandl, Judith N.; Monteiro, Joao P.; Vrisekoop, Nienke; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rgermain@nih.gov
FU NIAID, NIH, DHHS; Netherlands Organization for Scientific Research; NIH
Office of AIDS Research
FX The authors would like to thank J. Edwards for performing the CD5 sorts;
N. Subramanian for assistance with immunoblots; M. Levy and A. Yates for
statistical advice; Y. Belkaid for providing germ-free mice; P. Love for
providing AND Cd5-/- mice; M. K. Jenkins and M. Pepper for
providing L. monocytogenes Delta ActA, tetramer reagents, and assistance
with the tetramer bead enrichment methodology; the NIH Tetramer Facility
for providing pMHC tetramer reagents; G. Punkosdy and R. Ahmed for
providing LCMV-Armstrong; P. Thomas and P. Doherty for providing the
initial stock of influenza A virus; D. van Baarle for providing human
blood samples and reagents; and N. Nanlohy for providing assistance with
human experiments. We are grateful to I. Stefanova and M. Jenkins for
discussion and technical advice, J.D. Ashwell, G. I. Germain, M.J.
Lenardo, A. Poholek, and C. Reis e Sousa for their critical review of
the manuscript, and members of the Lymphocyte Biology Section for
intellectual support and critical discussions. This work was supported
by the Intramural Research Program of NIAID, NIH, DHHS, and also by the
Netherlands Organization for Scientific Research (N. V.) and by the NIH
Office of AIDS Research (J.N.M.). J.P.M. is a Pew Latin American Fellow
in the Biomedical Sciences. J.P.M., J.N.M., N. V., and R. N. G. designed
the study. J.N.M., J.P.M., and N. V. conducted all experiments. All
authors contributed to interpreting the data and writing the paper.
NR 51
TC 74
Z9 75
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 FEB 21
PY 2013
VL 38
IS 2
BP 263
EP 274
DI 10.1016/j.immuni.2012.09.011
PG 12
WC Immunology
SC Immunology
GA AA2RC
UT WOS:000330940800009
PM 23290521
ER
PT J
AU Cokic, VP
Smith, RD
Biancotto, A
Noguchi, CT
Puri, RK
Schechter, AN
AF Cokic, Vladan P.
Smith, Reginald D.
Biancotto, Angelique
Noguchi, Constance T.
Puri, Raj K.
Schechter, Alan N.
TI Globin gene expression in correlation with G protein-related genes
during erythroid differentiation
SO BMC GENOMICS
LA English
DT Article
DE G protein; G protein-coupled receptors; Erythroid progenitors; Ontogeny;
Globins
ID SOLUBLE GUANYLYL CYCLASE; NITRIC-OXIDE-SYNTHASE; COUPLED RECEPTOR;
FETAL-HEMOGLOBIN; K562 CELLS; BETA(2)-ADRENERGIC RECEPTOR; DEPENDENT
ACTIVATION; HEMATOPOIETIC-CELLS; BINDING PROTEIN; CD34(+) CELLS
AB Background: The guanine nucleotide binding protein (G protein)-coupled receptors (GPCRs) regulate cell growth, proliferation and differentiation. G proteins are also implicated in erythroid differentiation, and some of them are expressed principally in hematopoietic cells. GPCRs-linked NO/cGMP and p38 MAPK signaling pathways already demonstrated potency for globin gene stimulation. By analyzing erythroid progenitors, derived from hematopoietic cells through in vitro ontogeny, our study intends to determine early markers and signaling pathways of globin gene regulation and their relation to GPCR expression.
Results: Human hematopoietic CD34(+) progenitors are isolated from fetal liver (FL), cord blood (CB), adult bone marrow (BM), peripheral blood (PB) and G-CSF stimulated mobilized PB (mPB), and then differentiated in vitro into erythroid progenitors. We find that growth capacity is most abundant in FL- and CB-derived erythroid cells. The erythroid progenitor cells are sorted as 100% CD71(+), but we did not find statistical significance in the variations of CD34, CD36 and GlyA antigens and that confirms similarity in maturation of studied ontogenic periods. During ontogeny, beta-globin gene expression reaches maximum levels in cells of adult blood origin (176 fmol/mu g), while gamma-globin gene expression is consistently up-regulated in CB-derived cells (60 fmol/mu g). During gamma-globin induction by hydroxycarbamide, we identify stimulated GPCRs (PTGDR, PTGER1) and GPCRs-coupled genes known to be activated via the cAMP/PKA (ADIPOQ), MAPK pathway (JUN) and NO/cGMP (PRPF18) signaling pathways. During ontogeny, GPR45 and ARRDC1 genes have the most prominent expression in FL-derived erythroid progenitor cells, GNL3 and GRP65 genes in CB-derived cells (high gamma-globin gene expression), GPR110 and GNG10 in BM-derived cells, GPR89C and GPR172A in PB-derived cells, and GPR44 and GNAQ genes in mPB-derived cells (high beta-globin gene expression).
Conclusions: These results demonstrate the concomitant activity of GPCR-coupled genes and related signaling pathways during erythropoietic stimulation of globin genes. In accordance with previous reports, the stimulation of GPCRs supports the postulated connection between cAMP/PKA and NO/cGMP pathways in activation of.-globin expression, via JUN and p38 MAPK signaling.
C1 [Cokic, Vladan P.] Univ Belgrade, Inst Med Res, Lab Expt Hematol, Belgrade 11129, Serbia.
[Smith, Reginald D.] GE Global Res Ctr, Niskayuna, NY USA.
[Biancotto, Angelique] NHLBI, Ctr Human Immunol, NIH, Bethesda, MD 20892 USA.
[Noguchi, Constance T.; Schechter, Alan N.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
[Puri, Raj K.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
RP Cokic, VP (reprint author), Univ Belgrade, Inst Med Res, Lab Expt Hematol, Dr Subotica 4, Belgrade 11129, Serbia.
EM vl@imi.bg.ac.rs
OI Schechter, Alan N/0000-0002-5235-9408
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; Serbian Ministry of Education and Science
[175053]
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases and by
grant from the Serbian Ministry of Education and Science [175053].
NR 46
TC 6
Z9 6
U1 0
U2 1
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 FEB 20
PY 2013
VL 14
AR 116
DI 10.1186/1471-2164-14-116
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 109WV
UT WOS:000316401900001
PM 23425329
ER
PT J
AU Yamazaki, Y
Schonherr, C
Varshney, GK
Dogru, M
Hallberg, B
Palmer, RH
AF Yamazaki, Yasuo
Schoenherr, Christina
Varshney, Gaurav K.
Dogru, Murat
Hallberg, Bengt
Palmer, Ruth H.
TI Goliath family E3 ligases regulate the recycling endosome pathway via
VAMP3 ubiquitylation
SO EMBO JOURNAL
LA English
DT Article
DE E3 ubiquitin ligase; goliath; RING domain; SNARE; VAMP3
ID MEMBRANE-FUSION; SNARE COMPLEX; UBIQUITIN LIGASES; MEDIATED CLEAVAGE;
CRYSTAL-STRUCTURE; CELL-MIGRATION; ZINC-FINGER; GENOME-WIDE; DROSOPHILA;
PROTEIN
AB Diverse cellular processes depend on endocytosis, intracellular vesicle trafficking, sorting and exocytosis, processes regulated post-transcriptionally by modifications such as phosphorylation and ubiquitylation. In addition to sorting to the lysosome, cargo is recycled to the plasma membrane via recycling endosomes. Here, we describe a role of the goliath gene family of protease-associated (PA) domain E3 ligases in regulating recycling endosome trafficking. The two Drosophila members of this family-Goliath and Godzilla(CG10277) - are located on endosomes, and both ectopic expression and loss-of-function lead to the accumulation of Rab5-positive giant endosomes. Furthermore, the human homologue RNF167 exhibits similar behaviour. We show that the soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) protein VAMP3 is a target of these ubiquitin ligases, and that recycling endosome trafficking is abrogated in response to their activity. Furthermore, mutation of the Godzilla ubiquitylation target lysines on VAMP3 abrogates the formation of enlarged endosomes induced by either Godzilla or RNF167. Thus, Goliath ubiquitin ligases play a novel role in regulating recycling endosome trafficking via ubiquitylation of the VAMP3 SNARE protein. The EMBO Journal (2013) 32, 524-537. doi: 10.1038/emboj.2013.1; Published online 25 January 2013
C1 [Yamazaki, Yasuo; Schoenherr, Christina; Dogru, Murat; Hallberg, Bengt; Palmer, Ruth H.] Umea Univ, Dept Mol Biol, S-90187 Umea, Sweden.
[Varshney, Gaurav K.] NHGRI, Dev Genom Sect, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Palmer, RH (reprint author), Umea Univ, Dept Mol Biol, S-90187 Umea, Sweden.
EM ruth.palmer@ucmp.umu.se
RI Varshney, Gaurav/L-5261-2014;
OI Varshney, Gaurav K./0000-0002-0429-1904
FU Swedish Cancer Society [11-0336]; Children's Cancer Foundation [10/065];
Swedish Research Council [621-2011-5181]; Lions Cancer Society, Umea;
Association for International Cancer Research [08-0177]
FX This work has been supported by grants from the Swedish Cancer Society
(RHP 11-0336), the Children's Cancer Foundation (RHP 10/065), the
Swedish Research Council (RHP 621-2011-5181), Lions Cancer Society,
Umea, Association for International Cancer Research (RHP 08-0177). RHP
is a Swedish Cancer Foundation Research Fellow.
NR 57
TC 8
Z9 9
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD FEB 20
PY 2013
VL 32
IS 4
BP 524
EP 537
DI 10.1038/emboj.2013.1
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 110SX
UT WOS:000316467200006
PM 23353890
ER
PT J
AU Keren-Kaplan, T
Attali, I
Estrin, M
Kuo, LS
Farkash, E
Jerabek-Willemsen, M
Blutraich, N
Artzi, S
Peri, A
Freed, EO
Wolfson, HJ
Prag, G
AF Keren-Kaplan, Tal
Attali, Ilan
Estrin, Michael
Kuo, Lillian S.
Farkash, Efrat
Jerabek-Willemsen, Moran
Blutraich, Noa
Artzi, Shay
Peri, Aviyah
Freed, Eric O.
Wolfson, Haim J.
Prag, Gali
TI Structure-based in silico identification of ubiquitin-binding domains
provides insights into the ALIX-V: ubiquitin complex and retrovirus
budding
SO EMBO JOURNAL
LA English
DT Article
DE computational analyses; in silico scan; protein trafficking; ubiquitin;
virus budding
ID FIT BACKBONE REFINEMENT; MOLECULAR DOCKING; FUNCTIONAL REPLACEMENT; CUE
DOMAIN; ESCRT-III; PROTEIN; RECOGNITION; HIV-1; ENDOCYTOSIS; PERMEASE
AB The ubiquitylation signal promotes trafficking of endogenous and retroviral transmembrane proteins. The signal is decoded by a large set of ubiquitin (Ub) receptors that tether Ub-binding domains (UBDs) to the trafficking machinery. We developed a structure-based procedure to scan the protein data bank for hidden UBDs. The screen retrieved many of the known UBDs. Intriguingly, new potential UBDs were identified, including the ALIX-V domain. Pull-down, cross-linking and E3-independent ubiquitylation assays biochemically corroborated the in silico findings. Guided by the output model, we designed mutations at the postulated ALIX-V: Ub interface. Biophysical affinity measurements using microscale-thermophoresis of wild-type and mutant proteins revealed some of the interacting residues of the complex. ALIX-V binds mono-Ub with a K-d of 119 mu M. We show that ALIX-V oligomerizes with a Hill coefficient of 5.4 and IC50 of 27.6 mu M and that mono-Ub induces ALIX-V oligomerization. Moreover, we show that ALIX-V preferentially binds K63 di-Ub compared with mono-Ub and K48 di-Ub. Finally, an in vivo functionality assay demonstrates the significance of ALIX-V: Ub interaction in equine infectious anaemia virus budding. These results not only validate the new procedure, but also demonstrate that ALIX-V directly interacts with Ub in vivo and that this interaction can influence retroviral budding. The EMBO Journal (2013) 32, 538-551. doi: 10.1038/emboj.2013.4; Published online 29 January 2013
C1 [Keren-Kaplan, Tal; Attali, Ilan; Blutraich, Noa; Artzi, Shay; Prag, Gali] Tel Aviv Univ, Dept Biochem & Mol Biol, IL-69978 Tel Aviv, Israel.
[Keren-Kaplan, Tal; Attali, Ilan; Blutraich, Noa; Artzi, Shay; Prag, Gali] Tel Aviv Univ, George S Wise Fac Life Sci, Rich Inst Struct Biol, IL-69978 Tel Aviv, Israel.
[Estrin, Michael; Farkash, Efrat; Peri, Aviyah; Wolfson, Haim J.] Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel.
[Kuo, Lillian S.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Natl Lab Canc Res, Frederick, MD 21701 USA.
[Jerabek-Willemsen, Moran] NanoTemper Technol GmbH, Munich, Germany.
RP Prag, G (reprint author), Tel Aviv Univ, Dept Biochem & Mol Biol, IL-69978 Tel Aviv, Israel.
EM prag@tau.ac.il
FU Israeli Science Foundation [1695/08, 464/11]; EC FP7 Marie Curie
International Reintegration Grant [PIRG03-GA-2008-231079]; Israeli
Ministry of Health [5108]; Marianna and Jorge Saia Fund for HIV and
Parkinson Diseases; Center for Cancer Research, National Cancer
Institute, NIH; Intramural AIDS Targeted Antiviral Programme; Israel
Science Foundation (ISF) [1403/09]; Minerva-Minkowski Center for
Geometry; Adams Fellowship Fund
FX We wish to thank Neta Tanner and Bella Zion for technical help and James
Hurley for kindly providing the pGST-ALIX-V vector. This research was
supported by grants from the Israeli Science Foundation (grants numbers
1695/08 and 464/11), from the EC FP7 Marie Curie International
Reintegration Grant (PIRG03-GA-2008-231079), from the Israeli Ministry
of Health (5108), and the Marianna and Jorge Saia Fund for HIV and
Parkinson Diseases to GP. The Constantiner Institute for Molecular
Genetics for travel support to TKK Research in the EOF laboratory is
supported by the Intramural Research Programme of the Center for Cancer
Research, National Cancer Institute, NIH, and by the Intramural AIDS
Targeted Antiviral Programme. The Research of HJW was partially
supported by Israel Science Foundation (ISF grant no. 1403/09) and the
Minerva-Minkowski Center for Geometry. EF was supported by the Adams
Fellowship Fund.
NR 59
TC 26
Z9 27
U1 1
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0261-4189
EI 1460-2075
J9 EMBO J
JI Embo J.
PD FEB 20
PY 2013
VL 32
IS 4
BP 538
EP 551
DI 10.1038/emboj.2013.4
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 110SX
UT WOS:000316467200007
PM 23361315
ER
PT J
AU Wendel, SK
Mullis, CE
Eshleman, SH
Blankson, JN
Moore, RD
Keruly, JC
Brookmeyer, R
Quinn, TC
Laeyendecker, O
AF Wendel, Sarah K.
Mullis, Caroline E.
Eshleman, Susan H.
Blankson, Joel N.
Moore, Richard D.
Keruly, Jeanne C.
Brookmeyer, Ron
Quinn, Thomas C.
Laeyendecker, Oliver
TI Effect of Natural and ARV-Induced Viral Suppression and Viral
Breakthrough on Anti-HIV Antibody Proportion and Avidity in Patients
with HIV-1 Subtype B Infection
SO PLOS ONE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; BED-ENZYME IMMUNOASSAY; ANTIRETROVIRAL
THERAPY; ELITE SUPPRESSORS; SEROCONVERSION; INDIVIDUALS; CHALLENGES;
PREVENTION; MARYLAND; ASSAYS
AB Background: Viral suppression and viral breakthrough impact the humoral immune response to HIV infection. We evaluated the impact of viral suppression and viral breakthrough on results obtained with two cross-sectional HIV incidence assays.
Methods: All samples were collected from adults in the US who were HIV infected for >2 years. Samples were tested with the BED capture enzyme immunoassay (BED-CEIA) which measures the proportion of IgG that is HIV-specific, and with an antibody avidity assay based on the Genetic Systems 1/2+ O ELISA. We tested 281 samples: (1) 30 samples from 18 patients with natural control of HIV-1 infection known as elite controllers or suppressors (2) 72 samples from 18 adults on antiretroviral therapy (ART), with 1 sample before and 2-6 samples after ART initiation, and (3) 179 samples from 20 virally-suppressed adults who had evidence of viral breakthrough receiving ART (>400 copies/ml HIV RNA) and with subsequent viral suppression.
Results: For elite suppressors, 10/18 had BED-CEIA values <0.8 normalized optical density units (OD-n) and these values did not change significantly over time. For patients receiving ART, 14/18 had BED-CEIA values that decreased over time, with a median decrease of 0.42 OD-n (range 0.10 to 0.63)/time point receiving ART. Three patterns of BED-CEIA values were observed during viral breakthrough: (1) values that increased then returned to pre-breakthrough values when viral suppression was re-established, (2) values that increased after viral breakthrough, and (3) values that did not change with viral breakthrough.
Conclusions: Viral suppression and viral breakthrough were associated with changes in BED-CEIA values, reflecting changes in the proportion of HIV-specific IgG. These changes can result in misclassification of patients with long-term HIV infection as recently infected using the BED-CEIA, thereby influencing a falsely high value for cross-sectional incidence estimates.
C1 [Wendel, Sarah K.; Quinn, Thomas C.; Laeyendecker, Oliver] NIAID, Div Intramural Res, NIH, Baltimore, MD USA.
[Mullis, Caroline E.; Blankson, Joel N.; Moore, Richard D.; Keruly, Jeanne C.; Quinn, Thomas C.; Laeyendecker, Oliver] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Brookmeyer, Ron] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA.
RP Laeyendecker, O (reprint author), NIAID, Div Intramural Res, NIH, Baltimore, MD USA.
EM olaeyen1@jhmi.edu
RI Laeyendecker, Oliver/B-9331-2009;
OI Laeyendecker, Oliver/0000-0002-6429-4760
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH); HIV
Prevention Trials Network; NIAID [R01-AI-80328, R24-AI-067039]; National
Institutes of Child Health and Human Development; National Institute on
Drug Abuse (NIDA) [R01-DA-11602]; National Institute of Mental Health;
Office of AIDS Research, of the NIH, Department of Health and Human
Services [UM1-AI068613]; National Institute on Alcohol Abuse and
Alcoholism [R01-AA16893]
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH). Additional support was provided by the HIV
Prevention Trials Network sponsored by NIAID, National Institutes of
Child Health and Human Development, National Institute on Drug Abuse
(NIDA), National Institute of Mental Health, and Office of AIDS
Research, of the NIH, Department of Health and Human Services
(UM1-AI068613). The Johns Hopkins HIV Clinical Practice Cohort was
supported by NIDA (R01-DA-11602), National Institute on Alcohol Abuse
and Alcoholism (R01-AA16893), NIAID (R01-AI-80328) and NIAID
(R24-AI-067039). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 30
TC 17
Z9 17
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 FEB 20
PY 2013
VL 8
IS 2
AR e55525
DI 10.1371/journal.pone.0055525
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 093IE
UT WOS:000315184200020
PM 23437058
ER
PT J
AU Morse, CG
Dodd, LE
Nghiem, K
Costello, R
Csako, G
Lane, HC
Lozier, JN
Kovacs, JA
AF Morse, Caryn G.
Dodd, Lori E.
Nghiem, Khanh
Costello, Rene
Csako, Gyorgy
Lane, H. Clifford
Lozier, Jay N.
Kovacs, Joseph A.
TI Elevations in D-dimer and C-reactive protein are associated with the
development of osteonecrosis of the hip in HIV-infected adults
SO AIDS
LA English
DT Article
DE C-reactive protein; D-dimer; HIV; osteonecrosis
ID HUMAN-IMMUNODEFICIENCY-VIRUS; FEMORAL-HEAD; COAGULATION BIOMARKERS;
ANTIRETROVIRAL THERAPY; DISEASE; BONE; HYPOFIBRINOLYSIS; SENSITIVITY;
INHIBITOR; MORTALITY
AB Background: A high incidence of nontraumatic osteonecrosis has been reported in HIV-infected patients. We investigated the levels of D-dimer and C-reactive protein (CRP) in a cohort of HIV-infected adults with and without osteonecrosis of the femoral head.
Methods: Forty-three HIV-infected patients with osteonecrosis of the femoral head and a comparison group of 50 HIV-infected patients with negative MRI of the hips and for whom serial plasma samples were available were included. D-dimer and CRP levels were measured prior to and at the time of diagnosis for osteonecrosis patients, at the time of negative MRI of the hips for controls, and at least 6 months later for both groups.
Results: Biomarker levels were elevated at the time of diagnosis in the osteonecrosis cohort compared with controls. Median D-dimer value was 0.32 mu g/ml in the osteonecrosis group compared with less than 0.22 mu g/ml in the control group (P = 0.016). For CRP, the corresponding values were 2.52 mg/l and 1.23 mg/l (P = 0.003). Postdiagnosis, D-dimer and CRP levels were also elevated in the osteonecrosis patients compared with controls. Linear regression demonstrated a rise in D-dimer levels from prediagnosis to diagnosis in the osteonecrosis patients whereas CRP levels did not change significantly over time.
Conclusion: Compared to controls, patients who developed osteonecrosis had elevated levels of D-dimer and CRP at diagnosis. D-dimer levels increased whereas CRP levels did not change significantly from prediagnosis to diagnosis. These data suggest that patients with higher levels of inflammation are at an increased risk of osteonecrosis. (C) 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2013, 27: 591-595
C1 [Morse, Caryn G.; Kovacs, Joseph A.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Dodd, Lori E.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
[Nghiem, Khanh; Costello, Rene; Csako, Gyorgy; Lozier, Jay N.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Lane, H. Clifford] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA.
RP Morse, CG (reprint author), Bldg 10,Room 5A06,MSC 1403, Bethesda, MD 20892 USA.
EM cmorse@mail.nih.gov
OI Morse, Caryn/0000-0002-1177-4365
FU NIH Clinical Center; National Institute of Allergy and Infectious
Diseases
FX This research was supported by the Intramural Research Programs of the
NIH Clinical Center and the National Institute of Allergy and Infectious
Diseases.
NR 23
TC 6
Z9 6
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD FEB 20
PY 2013
VL 27
IS 4
BP 591
EP 595
DI 10.1097/QAD.0b013e32835c206a
PG 5
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 094SM
UT WOS:000315284100011
PM 23169328
ER
PT J
AU Lacombe, JM
Boue, F
Grabar, S
Viget, N
Gazaignes, S
Lascaux-Cametz, AS
Pacanowski, J
Partisani, M
Launay, O
Matheron, S
Rosenthal, E
Rouveix, E
Tattevin, P
de Truchis, P
Costagliola, D
Goedert, JJ
AF Lacombe, Jean-Marc
Boue, Francois
Grabar, Sophie
Viget, Nathalie
Gazaignes, Sandrine
Lascaux-Cametz, Anne-Sophie
Pacanowski, Jerome
Partisani, Marialuisa
Launay, Odile
Matheron, Sophie
Rosenthal, Eric
Rouveix, Elisabeth
Tattevin, Pierre
de Truchis, Pierre
Costagliola, Dominique
Goedert, James J.
TI Risk of Kaposi sarcoma during the first months on combination
antiretroviral therapy
SO AIDS
LA English
DT Article
DE combination antiretroviral therapy; immune reconstitution; inflammatory
syndrome; Kaposi sarcoma; Pneumocystis jiroveci pneumonia; prospective
cohort study
ID RECONSTITUTION INFLAMMATORY SYNDROME; CD4(+) T-CELLS; IMMUNE
RECONSTITUTION; HOMOSEXUAL-MEN; HIV; HERPESVIRUS; PREDICTORS; INFECTION;
LYMPHOMA; SURVIVAL
AB Objective: To determine whether incident AIDS-defining Kaposi sarcoma or Pneumocystis jiroveci pneumonia (PJP) is associated with combination antiretroviral therapy (cART) initiation.
Design: Compare risk for Kaposi sarcoma and PJP by time on cART and CD4 reconstitution.
Methods: In the FHDH-ANRS CO4 cohort (N = 66 369), Kaposi sarcoma (N = 1811) and PJP (N = 1718) incidence rates were computed by demographic and HIV strata. Crude and adjusted relative risk (RR) with 95% confidence intervals (CIs) following cART initiation were calculated by Poisson regression with untreated patients during 1996-2009 as reference. CD4 cell counts were compared by Wilcoxon rank sum tests.
Results: The risk of Kaposi sarcoma was very high during months 1-3 on cART (N = 160, RRCrude 3.94, 95% Cl 3.26-4.76), which was incompletely attenuated by adjustment for demographics and contemporaneous CD4 cell count (RRAdj 1.25, 95% Cl 1.02-1.53). Corresponding PJP risk was minimally elevated (N = 84, RRCrude 1.80, 95% Cl 1.42-2.30) and markedly reduced with adjustment on the same variables and PJP prophylaxis (RRAdj 0.52, Cl 0.41-0.67). HIV load had no added effect. Median CD4 cell count at cART initiation was much lower in patients with incident Kaposi sarcoma (82 cells/mu l) or PJP (61 cells/mu l) within 3 months than in those who did not develop these conditions (> 250 cells/mu l). Notably, median CD4 cell count change was +44 cells/mu l per month with incident Kaposi sarcoma within 3 months of cART initiation versus 0 cells/mu l per month with incident PJP (P = 0.0003).
Conclusion: Failure of CD4 cell count reconstitution during months 1-3 on cART fully accounted for incident PJP. In contrast, there were 1.6 additional Kaposi sarcoma cases per 1000 person-years during months 1-3 on cART, suggesting that immune reconstitution may contribute to the risk for AIDS-defining Kaposi sarcoma. (C) 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2013, 27:635-643
C1 [Lacombe, Jean-Marc] Univ Paris 06, INSERM, UMR S 943, INSERM TRANSFERT, Paris, France.
[Boue, Francois] Univ Paris Sud, Serv Med Interne & Immunol Clin, Hop Antoine Beclere, AP HP, Clamart, France.
[Grabar, Sophie] Univ Paris 05, Grp Hosp Cochin Hotel Dieu, AP HP, Unite Biostat & Epidemiol,INSERM UMR S 943, Paris, France.
[Viget, Nathalie] Ctr Hosp Tourcoing, Serv Univ Malad Infect & Voyage, Tourcoing, France.
[Gazaignes, Sandrine] Hop St Louis, AP HP, Serv Malad Infect & Trop, Paris, France.
[Lascaux-Cametz, Anne-Sophie] Hop Henri Mondor, AP HP, Serv Immunol Clin, F-94010 Creteil, France.
[Pacanowski, Jerome] Hop St Antoine, AP HP, Serv Malad Infect & Trop, F-75571 Paris, France.
[Partisani, Marialuisa] Hop Univ Strasbourg, Le Trait Union Ctr Soins Infect VIH, Strasbourg, France.
[Launay, Odile] Univ Paris 05, Hop Cochin, AP HP, Paris, France.
[Matheron, Sophie] Univ Paris 07, Hop Bichat Claude Bernard, AP HP, Serv Malad Infect & Trop, Paris, France.
[Rosenthal, Eric] Univ Nice Sophia Antipolis, Dept Med Interne, Hop Archet, Nice, France.
[Rouveix, Elisabeth] Hop Ambroise Pare, Serv Med Interne, Boulogne, France.
[Tattevin, Pierre] CHU Pontchaillou, Serv Malad Infect & Reanimat Med, Rennes, France.
[de Truchis, Pierre] Hop Raymond Poincare, AP HP, Serv Med Aigue Specialisee, Garches, France.
[Costagliola, Dominique] Univ Paris 06, INSERM, UMR S 943, Paris, France.
RP Goedert, JJ (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7068, Rockville, MD 20852 USA.
EM goedertj@mail.nih.gov
RI Costagliola, Dominique/H-5849-2011; Matheron, Sophie/D-7420-2017
OI Costagliola, Dominique/0000-0003-0765-0869; Matheron,
Sophie/0000-0001-7879-6553
FU Agence Nationale de Recherches sur le SIDA et les hepatites (ANRS);
INSERM; INSERM and the French Ministry of Health; ANRS; National Cancer
Institute; National Institutes of Health
FX The French Hospital Database on HIV is supported by Agence Nationale de
Recherches sur le SIDA et les hepatites (ANRS), INSERM and the French
Ministry of Health.; This work, specifically the French Hospital
Database on HIV, was supported by ANRS, INSERM and the French Ministry
of Health, and the Intramural Research Program of the National Cancer
Institute, National Institutes of Health.
NR 32
TC 12
Z9 13
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD FEB 20
PY 2013
VL 27
IS 4
BP 635
EP 643
DI 10.1097/QAD.0b013e32835cba6c
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 094SM
UT WOS:000315284100016
PM 23196937
ER
PT J
AU Schonfeld, SJ
de Gonzalez, AB
Visvanathan, K
Pfeiffer, RM
Anderson, WF
AF Schonfeld, Sara J.
de Gonzalez, Amy Berrington
Visvanathan, Kala
Pfeiffer, Ruth M.
Anderson, William F.
TI Declining Second Primary Ovarian Cancer After First Primary Breast
Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID UNITED-STATES; RANDOMIZED-TRIALS; WOMEN; RISK; SURVIVORS; SUBSEQUENT;
TRENDS
AB Purpose
Although ovarian cancer incidence rates have declined in the United States, less is known of ovarian cancer trends among survivors of breast cancer. Therefore, we examined second primary ovarian cancers after first primary breast cancer.
Methods
Data were obtained from the Surveillance, Epidemiology, and End Results program (1973 to 2008). Standardized incidence ratios (SIRs) were calculated as the observed numbers of ovarian cancers among survivors of breast cancer compared with the expected numbers in the general population. Absolute rates were measured as the incidence rates for second primary ovarian cancer by year of diagnosis of the first primary breast cancer adjusted for age of breast cancer diagnosis and years since diagnosis.
Results
SIRs for second primary ovarian cancer were elevated over the entire study period (SIR, 1.24; 95% CI, 1.2 to 1.3), whereas the absolute rates declined with an estimated annual percentage change near 1% (-1.34% to -0.09% per year). Secular trends for second ovarian cancers were similar after estrogen receptor (ER) -positive and ER-negative breast cancers, whereas the age-specific patterns varied significantly by ER expression (P for interaction < .001). The largest SIR was among women age less than 50 years with ER-negative breast cancer (SIR, 4.35; 95% CI, 3.5 to 5.4).
Conclusion
Persistently elevated SIRs along with decreasing absolute rates over the entire study period suggest that ovarian cancers in both the general population and survivors of breast cancer are declining in parallel, possibly because of common risk factor exposures. Analytic studies are needed to further assess the parallel overall trends and the age-specific interaction by ER expression. J Clin Oncol 31:738-743. (C) 2013 by American Society of Clinical Oncology
C1 [Schonfeld, Sara J.; de Gonzalez, Amy Berrington; Pfeiffer, Ruth M.; Anderson, William F.] NCI, DHHS, NIH, Bethesda, MD 20892 USA.
[Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Anderson, WF (reprint author), NCI, Dept Hlth & Human Serv, NIH, Execut Plaza S,Room 8036,6120 Execut Blvd, Rockville, MD 20852 USA.
EM wanderso@mail.nih.gov
FU National Institutes of Health, National Cancer Institute
FX Supported in part by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute.
NR 30
TC 3
Z9 4
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
BP 738
EP 743
DI 10.1200/JCO.2012.43.2757
PG 6
WC Oncology
SC Oncology
GA 091YT
UT WOS:000315086400023
PM 23284037
ER
PT J
AU Davidson-Moncada, JK
McDuffee, E
Roschewski, M
AF Davidson-Moncada, Jan K.
McDuffee, Emily
Roschewski, Mark
TI CD5(+) Diffuse Large B-Cell Lymphoma With Hemophagocytosis
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CLINICOPATHOLOGICAL CHARACTERISTICS; EXPRESSION; LYMPHOHISTIOCYTOSIS;
CHEMOTHERAPY; RITUXIMAB
C1 [Davidson-Moncada, Jan K.] NCI, Bethesda, MD 20892 USA.
[McDuffee, Emily; Roschewski, Mark] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
RP Davidson-Moncada, JK (reprint author), NCI, Bethesda, MD 20892 USA.
OI Roschewski, Mark/0000-0003-0278-2635
NR 30
TC 3
Z9 3
U1 0
U2 2
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 FEB 20
PY 2013
VL 31
IS 6
BP E76
EP E79
DI 10.1200/JCO.2012.44.2301
PG 4
WC Oncology
SC Oncology
GA 091YT
UT WOS:000315086400003
PM 23182983
ER
PT J
AU Baydyuk, M
Xie, YX
Tessarollo, L
Xu, BJ
AF Baydyuk, Maryna
Xie, Yuxiang
Tessarollo, Lino
Xu, Baoji
TI Midbrain-Derived Neurotrophins Support Survival of Immature Striatal
Projection Neurons
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CRE RECOMBINASE; BASAL GANGLIA; CELL-DEATH; BRAIN; MICE; RECEPTOR; TRKB;
HIPPOCAMPAL; INNERVATION; EXPRESSION
AB Neuronal death occurs at several stages during embryogenesis and early postnatal development; however, it is unknown how the survival of immature neurons at their origin is regulated before these cells migrate to their final destination. Striatal projection neurons, known as medium-sized spiny neurons (MSNs), in both the direct and indirect pathways are generated in the lateral ganglionic eminence (LGE). Here we report that brain-derived neurotrophic factor and neurotrophin-3 are anterogradely transported from midbrain dopaminergic neurons and support the survival of immature MSNs of the indirect and direct pathways, respectively, in the developing mouse striatum and LGE. These results reveal a novel mode of neurotrophic action in the nervous system by linking neurotrophins to the survival of immature neurons at their origin, while also suggesting that innervating neurons may control the size of their targeting neuronal population in the brain.
C1 [Baydyuk, Maryna; Xie, Yuxiang; Xu, Baoji] Georgetown Univ, Dept Physiol & Pharmacol, Med Ctr, Washington, DC 20057 USA.
[Tessarollo, Lino] NCI, Neural Dev Sect, Ctr Canc Res, Frederick, MD 21702 USA.
RP Xu, BJ (reprint author), Georgetown Univ, Dept Physiol & Pharmacol, Med Ctr, 3900 Reservoir Rd NW, Washington, DC 20057 USA.
EM bx3@georgetown.edu
FU US National Institutes of Health [R01 NS050596]
FX This work was supported by a grant from the US National Institutes of
Health to B. X. (R01 NS050596). We thank Nicole Calakos for
Drd1a-tdTomato mice, Stefano Vicini for Drd2-EGFP mice, and Eric Huang
for Th-Cre mice.
NR 24
TC 9
Z9 10
U1 0
U2 3
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD FEB 20
PY 2013
VL 33
IS 8
BP 3363
EP 3369
DI 10.1523/JNEUROSCI.3687-12.2013
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 093MJ
UT WOS:000315195700012
PM 23426664
ER
PT J
AU Rhodes, SEV
Murray, EA
AF Rhodes, Sarah E. V.
Murray, Elisabeth A.
TI Differential Effects of Amygdala, Orbital Prefrontal Cortex, and
Prelimbic Cortex Lesions on Goal-Directed Behavior in Rhesus Macaques
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ANTERIOR CINGULATE CORTEX; REWARD-GUIDED BEHAVIOR; ORBITOFRONTAL CORTEX;
BASOLATERAL AMYGDALA; REINFORCER DEVALUATION; ACTION SELECTION; DOUBLE
DISSOCIATION; INSTRUMENTAL ACTION; DECISION-MAKING; FRONTAL-CORTEX
AB We assessed the involvement of the orbital prefrontal cortex (PFo), the prelimbic region of the medial prefrontal cortex (PL), and the amygdala in goal-directed behavior. Rhesus monkeys were trained on a task in which two different instrumental responses were linked to two different outcomes. One response, called "tap," required the monkeys to repeatedly touch a colored square on a video monitor to produce one kind of food reward. The other response, called " hold," required persistent contact of an identical stimulus, and it produced a different kind of food reward. After training, we assessed the effects of sensory-specific reinforcer devaluation as a way to probe each monkey's use of goal-directed behavior. In this procedure, monkeys were allowed to consume one of the two foods to satiety and were then tested for tap/hold preference under extinction. Unoperated control monkeys showed a reduction in the response associated with obtaining the devalued food, called the "devaluation effect," a hallmark of goal-directed behavior. Monkeys with bilateral lesions of PFo or the amygdala exhibited significantly reduced devaluation effects. Results from monkeys with PL lesions were equivocal. We conclude that both PFo and the amygdala play a significant role in goal-directed behavior in monkeys. Notably, the findings for PFo challenge the idea that orbital and medial prefrontal regions are exclusively dedicated to object-and action-based processes, respectively.
C1 [Rhodes, Sarah E. V.; Murray, Elisabeth A.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP Rhodes, SEV (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B-80,49 Convent Dr, Bethesda, MD 20892 USA.
EM sarah.rhodes@mail.nih.gov
OI Murray, Elisabeth/0000-0003-1450-1642
FU National Institute of Mental Health
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health. We thank Steven Wise and Janine
Simmons for their comments on a previous version of this manuscript. We
are grateful to Yogita Chudasama, Emily Howland, Alicia Izquierdo, Peter
Kaskan, Anna Prescott, Rachel Reoli, and Richard Saunders for help
during surgery. We also thank Renee Hill and the staff of the Nuclear
Magnetic Resonance Imaging Facility of the National Institute of
Neurological Disorders and Stroke for assistance obtaining MR scans.
Finally, we thank Ping-Yu Chen for help preparing figures and Yogita
Chudasama, Alicia Izquierdo, Peter Rudebeck, and Katherine Wright for
help with brain lesion reconstructions.
NR 56
TC 20
Z9 21
U1 1
U2 11
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 FEB 20
PY 2013
VL 33
IS 8
BP 3380
EP U570
DI 10.1523/JNEUROSCI.4374-12.2013
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 093MJ
UT WOS:000315195700014
PM 23426666
ER
PT J
AU Quaia, C
Sheliga, BM
Optican, LM
Cumming, BG
AF Quaia, Christian
Sheliga, Boris M.
Optican, Lance M.
Cumming, Bruce G.
TI Temporal Evolution of Pattern Disparity Processing in Humans
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID VERGENCE EYE-MOVEMENTS; MACAQUE AREA MT; VISUAL-CORTEX; STEREOSCOPIC
DEPTH; 2-DIMENSIONAL PATTERNS; HUMAN STEREOPSIS; SIMPLE CELLS; MOTION;
DYNAMICS; RESPONSES
AB Stereo matching, i.e., the matching by the visual system of corresponding parts of the images seen by the two eyes, is inherently a 2D problem. To gain insights into how this operation is carried out by the visual system, we measured, in human subjects, the reflexive vergence eye movements elicited by the sudden presentation of stereo plaids. We found compelling evidence that the 2D pattern disparity is computed by combining disparities first extracted within orientation selective channels. This neural computation takes 10 - 15 ms, and is carried out even when subjects perceive not a single plaid but rather two gratings in different depth planes (transparency). However, we found that 1D disparities are not always effectively combined: When spatial frequency and contrast of the gratings are sufficiently different pattern disparity is not computed, a result that cannot be simply attributed to the transparency of such stimuli. Based on our results, we propose that a narrow-band implementation of the IOC (Intersection of Constraints) rule (Fennema and Thompson, 1979; Adelson and Movshon, 1982), preceded by cross-orientation suppression, underlies the extraction of pattern disparity.
C1 [Quaia, Christian; Sheliga, Boris M.; Optican, Lance M.; Cumming, Bruce G.] NEI, Sensorimotor Res Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Quaia, C (reprint author), NEI, Sensorimotor Res Lab, NIH, Dept Hlth & Human Serv, 49 Convent Dr,Room 2A50, Bethesda, MD 20892 USA.
EM quaiac@nei.nih.gov
FU National Eye Institute, NIH, Department of Health and Human Services
FX This research was supported by the Intramural Research Program of the
National Eye Institute, NIH, Department of Health and Human Services.
NR 55
TC 3
Z9 3
U1 0
U2 5
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 FEB 20
PY 2013
VL 33
IS 8
BP 3465
EP 3476
DI 10.1523/JNEUROSCI.4318-12.2013
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 093MJ
UT WOS:000315195700022
PM 23426674
ER
PT J
AU Inaba, K
Mizuhiki, T
Setogawa, T
Toda, K
Richmond, BJ
Shidara, M
AF Inaba, Kiyonori
Mizuhiki, Takashi
Setogawa, Tsuyoshi
Toda, Koji
Richmond, Barry J.
Shidara, Munetaka
TI Neurons in Monkey Dorsal Raphe Nucleus Code Beginning and Progress of
Step-by-Step Schedule, Reward Expectation, and Amount of Reward Outcome
in the Reward Schedule Task
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ORBITOFRONTAL CORTEX; SEROTONERGIC SYSTEM; DELAYED REWARDS; SIGNALS;
RAT; IDENTIFICATION; INFORMATION; PROJECTIONS; MODULATION; ACTIVATION
AB The dorsal raphe nucleus is the major source of serotonin in the brain. It is connected to brain regions related to reward processing, and the neurons show activity related to predicted reward outcome. Clinical observations also suggest that it is important in maintaining alertness and its apparent role in addiction seems to be related to reward processing. Here, we examined whether the neurons in dorsal raphe carry signals about reward outcome and task progress during multitrial schedules. We recorded from 98 single neurons in dorsal raphe of two monkeys. The monkeys perform one, two, or three visual discrimination trials (schedule), obtaining one, two, or three drops of liquid. In the valid cue condition, the length and brightness of a visual cue indicated schedule progress and reward amount, respectively. In the random cue condition, the visual cue was randomly presented with respect to schedule length and reward amount. We found information encoded about (1) schedule onset, (2) reward expectation, (3) reward outcome, and (4) reward amount in the mean firing rates. Information theoretic analysis showed that the temporal variation of the neuronal responses contained additional information related to the progress of the schedule toward the reward rather than only discriminating schedule onset or reward/no reward. When considered in light of all that is known about the raphe in anatomy, physiology, and behavior, the rich encoding about both task progress and predicted reward outcome makes the raphe a strong candidate for providing signals throughout the brain to coordinate persistent goal-seeking behavior.
C1 [Inaba, Kiyonori; Mizuhiki, Takashi; Setogawa, Tsuyoshi; Toda, Koji; Shidara, Munetaka] Univ Tsukuba, Grad Sch Comprehens Human Sci, Doctoral Program Kansei Behav & Brain Sci, Tsukuba, Ibaraki 3058577, Japan.
[Inaba, Kiyonori; Setogawa, Tsuyoshi] Japan Soc Promot Sci, Tsukuba, Ibaraki 3058577, Japan.
[Mizuhiki, Takashi; Shidara, Munetaka] Univ Tsukuba, Fac Med, Tsukuba, Ibaraki 3058577, Japan.
[Richmond, Barry J.] NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Shidara, M (reprint author), Univ Tsukuba, Fac Med, 1-1-1 Tennoudai, Tsukuba, Ibaraki 3058577, Japan.
EM mshidara@md.tsukuba.ac.jp
FU MEXT of Japan [21119006, 17022052]; KAKENHI [22300138]; U.S. National
Institute of Mental Health
FX This work was supported by Grant-in-Aid for JSPS Fellows (21119006; K.
I.); Grant-in-Aid for Scientific Research on Priority Areas-System study
on higher order brain functions from MEXT of Japan (17022052; M. S.);
and KAKENHI (22300138; M. S.), the U.S. National Institute of Mental
Health intramural program (B. J. R.). We thank Dr. Noriyuki Higo at the
National Institute of Advanced Industrial Science and Technology (AIST)
for histological technique and Dr. Shigeru Ozaki at the University of
Tsukuba for comments. We also received generous support for MRI
examination from Dr. Keiji Matsuda in AIST.
NR 43
TC 17
Z9 18
U1 1
U2 5
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 FEB 20
PY 2013
VL 33
IS 8
BP 3477
EP 3491
DI 10.1523/JNEUROSCI.4388-12.2013
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 093MJ
UT WOS:000315195700023
PM 23426675
ER
PT J
AU Fadlallah, B
Chen, BD
Keil, A
Principe, J
AF Fadlallah, Bilal
Chen, Badong
Keil, Andreas
Principe, Jose
TI Weighted-permutation entropy: A complexity measure for time series
incorporating amplitude information
SO PHYSICAL REVIEW E
LA English
DT Article
ID APPROXIMATE ENTROPY; SEIZURES; EEG
AB Permutation entropy (PE) has been recently suggested as a novel measure to characterize the complexity of nonlinear time series. In this paper, we propose a simple method to address some of PE's limitations, mainly its inability to differentiate between distinct patterns of a certain motif and the sensitivity of patterns close to the noise floor. The method relies on the fact that patterns may be too disparate in amplitudes and variances and proceeds by assigning weights for each extracted vector when computing the relative frequencies associated with every motif. Simulations were conducted over synthetic and real data for a weighting scheme inspired by the variance of each pattern. Results show better robustness and stability in the presence of higher levels of noise, in addition to a distinctive ability to extract complexity information from data with spiky features or having abrupt changes in magnitude. DOI: 10.1103/PhysRevE.87.022911
C1 [Fadlallah, Bilal; Principe, Jose] Univ Florida, Dept Elect & Comp Engn, Computat NeuroEngn Lab, Gainesville, FL 32611 USA.
[Chen, Badong] Xi An Jiao Tong Univ, Inst Artificial Intelligence & Robot, Xian 710049, Peoples R China.
[Keil, Andreas] Univ Florida, NIMH, Ctr Study Emot & Attent, Dept Psychol, Gainesville, FL 32611 USA.
RP Fadlallah, B (reprint author), Univ Florida, Dept Elect & Comp Engn, Computat NeuroEngn Lab, Gainesville, FL 32611 USA.
EM bhf@cnel.ufl.edu; chenbd@mail.xjtu.edu.cn; principe@cnel.ufl.edu
RI Keil, Andreas/F-9427-2011; Chen, Badong/F-4211-2015
OI Keil, Andreas/0000-0002-4064-1924; Chen, Badong/0000-0003-1710-3818
FU U.S. National Science Foundation [IIS-0964197]; Lebanese Center for
Scientific Research (CNRS)
FX This work was supported by the U.S. National Science Foundation under
Grant No. IIS-0964197 and the Lebanese Center for Scientific Research
(CNRS). The authors thank Austin Brockmeier for useful discussion and
the anonymous reviewers for their constructive suggestions.
NR 20
TC 42
Z9 42
U1 3
U2 26
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 1539-3755
J9 PHYS REV E
JI Phys. Rev. E
PD FEB 20
PY 2013
VL 87
IS 2
AR 022911
DI 10.1103/PhysRevE.87.022911
PG 7
WC Physics, Fluids & Plasmas; Physics, Mathematical
SC Physics
GA 092VL
UT WOS:000315151000010
PM 23496595
ER
PT J
AU Thomason, ME
Dassanayake, MT
Shen, S
Katkuri, Y
Alexis, M
Anderson, AL
Yeo, LM
Mody, S
Hernandez-Andrade, E
Hassan, SS
Studholme, C
Jeong, JW
Romero, R
AF Thomason, Moriah E.
Dassanayake, Maya T.
Shen, Stephen
Katkuri, Yashwanth
Alexis, Mitchell
Anderson, Amy L.
Yeo, Lami
Mody, Swati
Hernandez-Andrade, Edgar
Hassan, Sonia S.
Studholme, Colin
Jeong, Jeong-Won
Romero, Roberto
TI Cross-Hemispheric Functional Connectivity in the Human Fetal Brain
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID RESTING-STATE NETWORKS; DEFICIT HYPERACTIVITY DISORDER; LOW-FREQUENCY
FLUCTUATIONS; DEFAULT NETWORK; INFANT BRAIN; COMPONENT ANALYSIS;
CINGULATE CORTEX; IN-UTERO; EXPOSURE; FETUS
AB Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.
C1 [Thomason, Moriah E.; Anderson, Amy L.] Wayne State Univ, Merrill Palmer Skillman Inst Child & Family Dev, Detroit, MI 48202 USA.
[Thomason, Moriah E.; Jeong, Jeong-Won] Wayne State Univ, Dept Pediat, Sch Med, Detroit, MI 48202 USA.
[Thomason, Moriah E.; Anderson, Amy L.; Yeo, Lami; Hernandez-Andrade, Edgar; Hassan, Sonia S.; Romero, Roberto] Natl Inst Child Hlth & Human Dev NICHD, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI 48202 USA.
[Dassanayake, Maya T.; Alexis, Mitchell] Wayne State Univ, Basic Med Sci Program, Sch Med, Detroit, MI 48202 USA.
[Shen, Stephen] Wayne State Univ, Sch Med, Detroit, MI 48202 USA.
[Katkuri, Yashwanth; Mody, Swati] Wayne State Univ, Dept Radiol, Sch Med, Detroit, MI 48202 USA.
[Yeo, Lami; Hernandez-Andrade, Edgar; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Sch Med, Detroit, MI 48202 USA.
[Studholme, Colin] Univ Washington, Dept Pediat & Neonatol, Seattle, WA 98105 USA.
[Studholme, Colin] Univ Washington, Dept Bioengn, Seattle, WA 98105 USA.
[Jeong, Jeong-Won] Wayne State Univ, Dept Neurol, Sch Med, Detroit, MI 48202 USA.
[Romero, Roberto] NICHD, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD 20814 USA.
RP Thomason, ME (reprint author), Wayne State Univ, Merrill Palmer Skillman Inst Child & Family Dev, Detroit, MI 48202 USA.
EM moriah@wayne.edu
FU Merrill Palmer Skillman Institute for Child and Family Development;
Department of Pediatrics, Wayne State University (WSU) School of
Medicine; WSU Perinatal Initiative; Intramural Research Program of the
Eunice Kennedy Shriver NICHD, NIH, Department of Health and Human
Services [N01-HD-2-3342]; NIH/NINDS [NS 055064]; WSU's Perinatology
Virtual Discovery Grant [P3018205]; WSU's Research Grant Program awards
FX This research was supported, in part, by the Merrill Palmer Skillman
Institute for Child and Family Development; the Department of
Pediatrics, Wayne State University (WSU) School of Medicine; the WSU
Perinatal Initiative; and the Intramural Research Program of the Eunice
Kennedy Shriver NICHD, NIH, Department of Health and Human Services
through contract N01-HD-2-3342. This project was also supported by
NIH/NINDS R01 grant NS 055064 (to C. S.), WSU's Perinatology Virtual
Discovery Grant (made possible by W. K. Kellogg Foundation award
P3018205), and WSU's Research Grant Program awards (to M. E. T.). The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the NICHD or the NIH.
NR 82
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U1 1
U2 10
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 FEB 20
PY 2013
VL 5
IS 173
AR 173ra24
DI 10.1126/scitranslmed.3004978
PG 10
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 094KQ
UT WOS:000315262000003
PM 23427244
ER
PT J
AU Duan, JB
Shi, JX
Ge, XJ
Dolken, L
Moy, W
He, DL
Shi, S
Sanders, AR
Ross, J
Gejman, PV
AF Duan, Jubao
Shi, Jianxin
Ge, Xijin
Doelken, Lars
Moy, Winton
He, Deli
Shi, Sandra
Sanders, Alan R.
Ross, Jeff
Gejman, Pablo V.
TI Genome-wide survey of interindividual differences of RNA stability in
human lymphoblastoid cell lines
SO SCIENTIFIC REPORTS
LA English
DT Article
ID HUMAN GENE-EXPRESSION; NEWLY SYNTHESIZED RNA; MESSENGER-RNA; MICROARRAY
ANALYSIS; MAMMALIAN-CELLS; NORMALIZATION METHODS; MENTAL-RETARDATION;
DECAY-RATES; ASSOCIATION; POPULATION
AB The extent to which RNA stability differs between individuals and its contribution to the interindividual expression variation remain unknown. We conducted a genome-wide analysis of RNA stability in seven human HapMap lymphoblastoid cell lines (LCLs) and analyzed the effect of DNA sequence variation on RNA half-life differences. Twenty-six percent of the expressed genes exhibited RNA half-life differences between LCLs at a false discovery rate (FDR) < 0.05, which accounted for similar to 37% of the gene expression differences between individuals. Nonsense polymorphisms were associated with reduced RNA half-lives. In genes presenting interindividual RNA half-life differences, higher coding GC3 contents (G and C percentages at the third-codon positions) were correlated with increased RNA half-life. Consistently, G and C alleles of single nucleotide polymorphisms (SNPs) in protein coding sequences were associated with enhanced RNA stability. These results suggest widespread interindividual differences in RNA stability related to DNA sequence and composition variation.
C1 [Duan, Jubao; Moy, Winton; He, Deli; Shi, Sandra; Sanders, Alan R.; Gejman, Pablo V.] NorthShore Univ HealthSyst Res Inst, Ctr Psychiat Genet, Evanston, IL 60201 USA.
[Duan, Jubao; Sanders, Alan R.; Gejman, Pablo V.] Univ Chicago, Dept Psychiat & Behav Sci, Chicago, IL 60637 USA.
[Shi, Jianxin] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Ge, Xijin] S Dakota State Univ, Dept Math & Stat, Brookings, SD 57007 USA.
[Doelken, Lars] Univ Cambridge, Dept Med, Addenbrookes Hosp, Cambridge CB2 0QQ, England.
[Ross, Jeff] Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA.
RP Duan, JB (reprint author), NorthShore Univ HealthSyst Res Inst, Ctr Psychiat Genet, Evanston, IL 60201 USA.
EM jduan@uchicago.edu
OI Ge, Steven/0000-0001-7406-3782
FU NorthShore University HealthSystem Research Career Development Award;
MRC [G1002523]; National Institute of Health [RC2MH090030, R01MH94091]
FX This work was supported by NorthShore University HealthSystem (formally
Evanston Northwestern Healthcare) Research Career Development Award to
J.D.; MRC Fellowship grant G1002523 to L.D.' and grants from National
Institute of Health (RC2MH090030 to A. R. S. and R01MH94091 to P. V.
G.). We thank Dr. Kai Wang (Zilkha Neurogenetic Institute, CA) for
bioinformatic assistance on gene annotation by ANOVAR.
NR 84
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U1 1
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD FEB 20
PY 2013
VL 3
AR 1318
DI 10.1038/srep01318
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092WI
UT WOS:000315153300001
PM 23422947
ER
PT J
AU Baker, SG
AF Baker, Stuart G.
TI Remarks on 'A simple decision analytic solution to the comparison of two
binary diagnostic tests' by Vickers et al.
SO STATISTICS IN MEDICINE
LA English
DT Letter
C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
RP Baker, SG (reprint author), NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
EM sb16i@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 4
TC 0
Z9 0
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD FEB 20
PY 2013
VL 32
IS 4
BP 718
EP 718
DI 10.1002/sim.5663
PG 1
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 076TK
UT WOS:000313980700017
PM 23341085
ER
PT J
AU Apolo, AB
Lee, YH
Cecchi, F
Agarwal, PK
Parnes, HL
Khadar, K
Summerell, A
Gulley, JL
Compton, K
Figg, WD
Dahut, WL
Bottaro, DP
AF Apolo, Andrea Borghese
Lee, Young H.
Cecchi, Fabiola
Agarwal, Piyush K.
Parnes, Howard L.
Khadar, Kattie
Summerell, Amelia
Gulley, James L.
Compton, Kathryn
Figg, William Douglas
Dahut, William L.
Bottaro, Donald P.
TI Preclinical and correlative studies of cabozantinib (XL184) in
urothelial cancer (UC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of
American-Society-of-Clinical-Oncology (ASCO)
CY FEB 14-16, 2013
CL Orlando, FL
SP Amer Soc Clin Oncol, Conquer Canc Fdn
C1 NCI, Bethesda, MD 20892 USA.
NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016
OI Gulley, James/0000-0002-6569-2912;
NR 0
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
SU S
MA 314
PG 1
WC Oncology
SC Oncology
GA AE0TR
UT WOS:000333679600314
ER
PT J
AU Couvillon, A
Beatson, MA
Harold, N
Karzai, FH
Madan, RA
Gulley, JL
Dahut, WL
AF Couvillon, Anna
Beatson, Melony A.
Harold, Nancy
Karzai, Fatima H.
Madan, Ravi Amrit
Gulley, James L.
Dahut, William L.
TI Feasibility of continuing docetaxel-based therapy in patients with
metastatic castrate-resistant prostate cancer (mCRPC) that experience
hypersensitivity reactions (HSR)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of
American-Society-of-Clinical-Oncology (ASCO)
CY FEB 14-16, 2013
CL Orlando, FL
SP Amer Soc Clin Oncol, Conquer Canc Fdn
C1 NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Lab Tumor Immunol & Biol, Med Oncol Branch, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
SU S
MA 132
PG 1
WC Oncology
SC Oncology
GA AE0TR
UT WOS:000333679600133
ER
PT J
AU Goodman, PJ
Thompson, IM
Tangen, CM
Parnes, HL
Godley, PA
Ford, LG
AF Goodman, Phyllis J.
Thompson, Ian Murchie
Tangen, Catherine M.
Parnes, Howard L.
Godley, Paul Alphonso
Ford, Leslie G.
TI Long-term survival of subjects in the prostate cancer prevention trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of
American-Society-of-Clinical-Oncology (ASCO)
CY FEB 14-16, 2013
CL Orlando, FL
SP Amer Soc Clin Oncol, Conquer Canc Fdn
C1 SWOG Stat Ctr, Seattle, WA USA.
Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
Univ N Carolina, Chapel Hill, NC USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
SU S
MA 10
PG 1
WC Oncology
SC Oncology
GA AE0TR
UT WOS:000333679600013
ER
PT J
AU Gulley, JL
Madan, RA
Stein, WD
Wilkerson, J
Dahut, WL
Heery, CR
Schlom, J
Wilding, G
DiPaola, RS
AF Gulley, James L.
Madan, Ravi Amrit
Stein, Wilfred Donald
Wilkerson, Julia
Dahut, William L.
Heery, Christopher Ryan
Schlom, Jeffrey
Wilding, George
DiPaola, Robert S.
TI Effect of PSA-tricom, a pox-viral vaccine in prostate cancer (PCa), on
tumor growth rates within 80 days after initiation in nonmetastatic PCa
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of
American-Society-of-Clinical-Oncology (ASCO)
CY FEB 14-16, 2013
CL Orlando, FL
SP Amer Soc Clin Oncol, Conquer Canc Fdn
C1 NCI, Tumor Immunol & Biol Lab, Med Oncol Branch, Bethesda, MD 20892 USA.
Hebrew Univ Jerusalem, Jerusalem, Israel.
NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
SU S
MA 57
PG 1
WC Oncology
SC Oncology
GA AE0TR
UT WOS:000333679600058
ER
PT J
AU Heath, EI
Mannuel, HD
Liu, G
Lara, P
Monk, JP
Flaig, TW
Zurita, AJ
Vaishampayan, UN
Stella, PJ
Smith, DW
Dobson, K
Hussain, A
Al-Janadi, A
Ivy, SP
Heilbrun, LK
AF Heath, Elisabeth I.
Mannuel, Heather Dorothy
Liu, Glenn
Lara, Primo
Monk, J. P.
Flaig, Thomas W.
Zurita, Amado J.
Vaishampayan, Ulka N.
Stella, Philip J.
Smith, Daryn W.
Dobson, Kimberlee
Hussain, Arif
Al-Janadi, Anas
Ivy, S. Percy
Heilbrun, Lance K.
TI Randomized phase II trial of docetaxel (Doc) and prednisone (Pred) with
or without AZD2171 (cediranib), in chemotherapy-naive, metastatic
castrate-resistant prostate cancer (mCRPC) (NCI 7451)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of
American-Society-of-Clinical-Oncology (ASCO)
CY FEB 14-16, 2013
CL Orlando, FL
SP Amer Soc Clin Oncol, Conquer Canc Fdn
C1 Karmanos Canc Inst, Detroit, MI USA.
Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
Univ Calif Davis, Sacramento, CA 95817 USA.
Ohio State Univ, Columbus, OH 43210 USA.
Univ Colorado Denver, Aurora, CO USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
Natl Surg Adjuvant Breast & Bowel Project, Ann Arbor, MI USA.
St Joseph Mercy Hlth Syst, Ann Arbor, MI USA.
Michigan State Univ, Dept Med, Lansing, MI USA.
NCI, Div Canc Treatment, Canc Therapy Evaluat Program, Invest Drug Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
SU S
MA 38
PG 1
WC Oncology
SC Oncology
GA AE0TR
UT WOS:000333679600040
ER
PT J
AU Heery, CR
Madan, RA
Bilusic, M
Kim, JW
Singh, NK
Rauckhorst, M
Steinberg, SM
Dahut, WL
Chen, C
DiPaola, RS
Stein, MN
Panicali, D
Hodge, JW
Schlom, J
Gulley, JL
AF Heery, Christopher Ryan
Madan, Ravi Amrit
Bilusic, Marijo
Kim, Joseph W.
Singh, Nishith K.
Rauckhorst, Myrna
Steinberg, Seth M.
Dahut, William L.
Chen, Clara
DiPaola, Robert S.
Stein, Mark N.
Panicali, Dennis
Hodge, James W.
Schlom, Jeffrey
Gulley, James L.
TI A phase II randomized clinical trial of samarium-153 EDTMP (Sm-153) with
or without PSA-TRICOM vaccine in metastatic castration-resistant
prostate cancer (mCRPC) after docetaxel
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of
American-Society-of-Clinical-Oncology (ASCO)
CY FEB 14-16, 2013
CL Orlando, FL
SP Amer Soc Clin Oncol, Conquer Canc Fdn
C1 NCI, Lab Tumor Immunol & Biol, Med Oncol Branch, Bethesda, MD 20892 USA.
NHLBI, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, CCR, NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD USA.
Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA.
Canc Inst New Jersey, New Brunswick, NJ USA.
Bavarian Nord ImmunoTherapeut, Mountain View, CA USA.
RI Hodge, James/D-5518-2015; Gulley, James/K-4139-2016
OI Hodge, James/0000-0001-5282-3154; Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 1
U2 4
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
SU S
MA 102
PG 1
WC Oncology
SC Oncology
GA AE0TR
UT WOS:000333679600103
ER
PT J
AU Truong, H
Nix, J
Smith, K
Mittal, A
Agarwal, P
AF Hong Truong
Nix, Jeffrey
Smith, Kamal
Mittal, Aayush
Agarwal, Piyush
TI Perioperative management of radical cystectomy patients: A questionnaire
survey of the American Urological Association members
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of
American-Society-of-Clinical-Oncology (ASCO)
CY FEB 14-16, 2013
CL Orlando, FL
SP Amer Soc Clin Oncol, Conquer Canc Fdn
C1 [Hong Truong; Nix, Jeffrey; Smith, Kamal; Mittal, Aayush; Agarwal, Piyush] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
SU S
MA 316
PG 1
WC Oncology
SC Oncology
GA AE0TR
UT WOS:000333679600316
ER
PT J
AU Karzai, FH
Adesunloye, B
Ning, YMM
Madan, RA
Gulley, JL
Apolo, AB
Beatson, MA
Couvillon, A
Harold, N
Parnes, HL
Arlen, PM
Wright, JJ
Chen, C
Dawson, NA
Figg, WD
Dahut, WL
AF Karzai, Fatima H.
Adesunloye, Bamidele
Ning, Yangmin M.
Madan, Ravi Amrit
Gulley, James L.
Apolo, Andrea Borghese
Beatson, Melony A.
Couvillon, Anna
Harold, Nancy
Parnes, Howard L.
Arlen, Philip M.
Wright, John Joseph
Chen, Clara
Dawson, Nancy Ann
Figg, William Douglas
Dahut, William L.
TI Use of supportive measures to improve outcome and decrease toxicity in
docetaxel-based antiangiogenesis combinations
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of
American-Society-of-Clinical-Oncology (ASCO)
CY FEB 14-16, 2013
CL Orlando, FL
SP Amer Soc Clin Oncol, Conquer Canc Fdn
C1 NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
NCI, US FDA, Silver Spring, MD USA.
NCI, Lab Tumor Immunol & Biol, Med Oncol Branch, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
Neogenix Oncol, Rockville, MD USA.
NCI, Rockville, MD USA.
NCI, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA.
Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA.
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016
OI Gulley, James/0000-0002-6569-2912;
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
SU S
MA 128
PG 1
WC Oncology
SC Oncology
GA AE0TR
UT WOS:000333679600129
ER
PT J
AU Kim, JW
Marte, JL
Bilusic, M
Singh, NK
Heery, CR
Madan, RA
Pazdur, M
McMahon, S
Rauckhorst, M
Schlom, J
Gulley, JL
AF Kim, Joseph W.
Marte, Jennifer L.
Bilusic, Marijo
Singh, Nishith K.
Heery, Christopher Ryan
Madan, Ravi Amrit
Pazdur, Mary
McMahon, Sheri
Rauckhorst, Myrna
Schlom, Jeffrey
Gulley, James L.
TI Safety profile of poxviral vaccines: NCI experience
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of
American-Society-of-Clinical-Oncology (ASCO)
CY FEB 14-16, 2013
CL Orlando, FL
SP Amer Soc Clin Oncol, Conquer Canc Fdn
C1 NCI, Lab Tumor Immunol & Biol, Med Oncol Branch, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
SU S
MA 85
PG 1
WC Oncology
SC Oncology
GA AE0TR
UT WOS:000333679600086
ER
PT J
AU Park, JC
Kurdziel, KA
Lindenberg, L
Gulley, JL
Madan, RA
Wood, LV
McKinney, Y
Choyke, PL
Dahut, WL
Apolo, AB
AF Park, Jong Chul
Kurdziel, Karen A.
Lindenberg, Liza
Gulley, James L.
Madan, Ravi Amrit
Wood, Lauren V.
McKinney, Yolanda
Choyke, Peter L.
Dahut, William L.
Apolo, Andrea Borghese
TI Preliminary results of a prospective study of 18F-NAF PET/CT in prostate
cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of
American-Society-of-Clinical-Oncology (ASCO)
CY FEB 14-16, 2013
CL Orlando, FL
SP Amer Soc Clin Oncol, Conquer Canc Fdn
C1 NCI, Bethesda, MD 20892 USA.
Ctr Canc Res, Mol Imaging Program, Bethesda, MD USA.
NIC, CCR, Bethesda, MD USA.
NCI, Lab Tumor Immunol & Biol, Med Oncol Branch, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
SU S
MA 103
PG 1
WC Oncology
SC Oncology
GA AE0TR
UT WOS:000333679600104
ER
PT J
AU Shuch, B
Asher, KP
Chen, C
Lin, K
Bratslavsky, G
Linehan, WM
Srinivasan, R
AF Shuch, Brian
Asher, Kevin P.
Chen, Clara
Lin, Kelly
Bratslavsky, Gennady
Linehan, W. Marston
Srinivasan, Ramaprasad
TI Clinical evaluation of 2-(F-18) fluoro-2 deoxy-D-glucose PET/CT in
hereditary leiomyomatosis and renal cell carcinoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of
American-Society-of-Clinical-Oncology (ASCO)
CY FEB 14-16, 2013
CL Orlando, FL
SP Amer Soc Clin Oncol, Conquer Canc Fdn
C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
SU S
MA 383
PG 1
WC Oncology
SC Oncology
GA AE0TR
UT WOS:000333679600380
ER
PT J
AU Shuch, B
Hanley, J
Lai, J
Setodji, CM
Vourganti, S
Chow, WH
Saigal, C
AF Shuch, Brian
Hanley, Janet
Lai, Julie
Setodji, Claude Messan
Vourganti, Srinivas
Chow, Wong Ho
Saigal, Christopher
TI Association of adverse health outcomes with partial and radical
nephrectomy: Is it time to reassess the "gold standard" for the small
renal mass?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of
American-Society-of-Clinical-Oncology (ASCO)
CY FEB 14-16, 2013
CL Orlando, FL
SP Amer Soc Clin Oncol, Conquer Canc Fdn
C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RAND Corp, Santa Monica, CA USA.
NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
SU S
MA 363
PG 1
WC Oncology
SC Oncology
GA AE0TR
UT WOS:000333679600361
ER
PT J
AU Shuch, B
Vourganti, S
Middleton, L
Linehan, WM
AF Shuch, Brian
Vourganti, Srinivas
Middleton, Lindsay
Linehan, W. Marston
TI Defining early-onset kidney cancer: Implications for genetic counseling
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of
American-Society-of-Clinical-Oncology (ASCO)
CY FEB 14-16, 2013
CL Orlando, FL
SP Amer Soc Clin Oncol, Conquer Canc Fdn
C1 [Shuch, Brian; Vourganti, Srinivas; Middleton, Lindsay; Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
SU S
MA 342
PG 1
WC Oncology
SC Oncology
GA AE0TR
UT WOS:000333679600342
ER
PT J
AU Vourganti, S
Harbin, A
Singer, EA
Shuch, B
Metwalli, AR
Agarwal, PK
AF Vourganti, Srinivas
Harbin, Andrew
Singer, Eric A.
Shuch, Brian
Metwalli, Adam R.
Agarwal, Piyush K.
TI Low-grade micropapillary urothelial carcinoma: Does it exist? A SEER
analysis of management and outcomes
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of
American-Society-of-Clinical-Oncology (ASCO)
CY FEB 14-16, 2013
CL Orlando, FL
SP Amer Soc Clin Oncol, Conquer Canc Fdn
C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
Georgetown Univ, Dept Urol, Washington, DC USA.
Canc Inst New Jersey, Urol Oncol Program, New Brunswick, NJ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
SU S
MA 315
PG 1
WC Oncology
SC Oncology
GA AE0TR
UT WOS:000333679600315
ER
PT J
AU Weintraub, M
Siddiqui, M
Vourganti, S
Shuch, B
Agarwal, P
Linehan, WM
AF Weintraub, Michael
Siddiqui, Minhaj
Vourganti, Srinivas
Shuch, Brian
Agarwal, Piyush
Linehan, W. Marston
TI Paragangliomas of the urinary bladder: Experience at the National Cancer
Institute
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of
American-Society-of-Clinical-Oncology (ASCO)
CY FEB 14-16, 2013
CL Orlando, FL
SP Amer Soc Clin Oncol, Conquer Canc Fdn
C1 [Weintraub, Michael; Siddiqui, Minhaj; Vourganti, Srinivas; Shuch, Brian; Agarwal, Piyush; Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2013
VL 31
IS 6
SU S
MA 307
PG 1
WC Oncology
SC Oncology
GA AE0TR
UT WOS:000333679600307
ER
PT J
AU Gangarossa, G
Espallergues, J
d'Exaerde, AD
El Mestikawy, S
Gerfen, CR
Herve, D
Girault, JA
Valjent, E
AF Gangarossa, Giuseppe
Espallergues, Julie
d'Exaerde, Alban de Kerchove
El Mestikawy, Salah
Gerfen, Charles R.
Herve, Denis
Girault, Jean-Antoine
Valjent, Emmanuel
TI Distribution and compartmental organization of GABAergic medium-sized
spiny neurons in the mouse nucleus accumbens
SO FRONTIERS IN NEURAL CIRCUITS
LA English
DT Article
DE medium-sized spiny neurons; BAC transgenic; nucleus accumbens; dopamine;
psychostimulant; ERK signaling; neural circuits
ID SIGNAL-REGULATED KINASE; SITU HYBRIDIZATION HISTOCHEMISTRY; VENTRAL
STRIATUM; DOPAMINE-RECEPTOR; RAT-BRAIN; STRIATOPALLIDAL NEURONS;
TYROSINE-HYDROXYLASE; GENE-EXPRESSION; SUBSTANCE-P; ADENOSINE-A2
RECEPTOR
AB The nucleus accumbens (NAc) is a critical brain region involved in many reward-related behaviors. The NAc comprises major compartments the core and the shell, which encompass several subterritories. GABAergic medium-sized spiny neurons (MSNs) constitute the output neurons of the NAc core and shell. While the functional organization of the NAc core outputs resembles the one described for the dorsal striatum, a simple classification of the NAc shell neurons has been difficult to define due to the complexity of the compartmental segregation of cells. We used a variety of BAC transgenic mice expressing enhanced green fluorescence (EGFP) or the Cre-recombinase (Cre) under the control of the promoter of dopamine D1, D2, and D3 receptors and of adenosine A2a receptor to dissect the microanatomy of the NAc. Moreover, using various immunological markers we characterized in detail the distribution of MSNs in the mouse NAc. In addition, cell-type specific extracellular signal-regulated kinase (ERK) phosphorylation in the NAc subterritories was analyzed following acute administration of SKF81297 (a D1R-like agonist), quinpirole (a D2 receptors (D2R)-like agonist), apomorphine (a non-selective DA receptor agonist), raclopride (a D2R-like antagonist), and psychostimulant drugs, including cocaine and d-amphetamine. Each drug generated a unique topography and cell-type specific activation of ERK in the NAc. Our results show the existence of marked differences in the receptor expression pattern and functional activation of MSNs within the shell subterritories. This study emphasizes the anatomical and functional heterogeneity of the NAc, which will have to be considered in its further study.
C1 [Gangarossa, Giuseppe; Espallergues, Julie; Valjent, Emmanuel] CNRS, UMR 5203, Inst Genom Fonct, Montpellier, France.
[Gangarossa, Giuseppe; Espallergues, Julie; Valjent, Emmanuel] INSERM, U661, Montpellier, France.
[Gangarossa, Giuseppe; Espallergues, Julie; Valjent, Emmanuel] Univ Montpellier I, UMR 5203, F-34094 Montpellier, France.
[Gangarossa, Giuseppe; Espallergues, Julie; Valjent, Emmanuel] Univ Montpellier 2, UMR 5203, F-34094 Montpellier, France.
[d'Exaerde, Alban de Kerchove] Univ Libre Brussels, Sch Med, Neurophysiol Lab, ULB Neurosci Inst, Brussels, Belgium.
[El Mestikawy, Salah] CNRS, UMR 7224, Paris, France.
[El Mestikawy, Salah] INSERM, U952, Paris, France.
[El Mestikawy, Salah] Univ Paris 06, UMR 7224, Paris, France.
[Gerfen, Charles R.] NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA.
[Herve, Denis; Girault, Jean-Antoine] INSERM, UMR S 839, Paris, France.
[Herve, Denis; Girault, Jean-Antoine] Univ Paris 06, UMR S 839, Paris, France.
[Herve, Denis; Girault, Jean-Antoine] Inst Fer Moulin, Paris, France.
RP Valjent, E (reprint author), Univ Montpellier I, INSERM, U661, F-34094 Montpellier, France.
EM emmanuel.valjent@igf.cnrs.fr
RI Girault, Jean-Antoine/F-7518-2013; HERVE, Denis/E-2929-2017;
OI Girault, Jean-Antoine/0000-0002-7900-1705; HERVE,
Denis/0000-0003-1376-1522; Gangarossa, Giuseppe/0000-0001-9045-2139
FU Inserm; ATIP-Avenir (Inserm); Sanofi-Aventis RD; Agence Nationale de la
Recherche [ANR-2010-JCJC-1412, ANR-BLAN08-1_346422]; Fondation pour la
recherche medicale (FRM); European Union; European research council
(ERC); FRS-FNRS (Belgium); ULB; Action de Recherche Concertee from the
CFWB; UM1
FX This work was supported by Inserm and grants from ATIP-Avenir (Inserm),
Sanofi-Aventis R&D, and from the Agence Nationale de la Recherche
(ANR-2010-JCJC-1412) to Emmanuel Valjent. Research in Jean-Antoine
Girault and Denis Herve lab was supported by grants from the Fondation
pour la recherche medicale (FRM), the Agence nationale de la recherche
(ANR-BLAN08-1_346422), European Union Framework program 7 (FP7, SynSys),
and the European research council (ERC). AdKdE is a Research Associate
of the FRS-FNRS (Belgium) and is supported by FRS-FNRS (Belgium), FER
from ULB, Action de Recherche Concertee from the CFWB. Julie
Espallergues was a recipient of a postdoctoral fellowship from UM1. We
are grateful to Laurent Fagni and Julie Perroy (Institut de Genomique
Fonctionnelle) for providing some transgenic mice used in this study. We
thank Frederic Gallardo (IGF) and Natacha Roblot, Rachida Boukhari, and
Yohann Bertelle (IFM) for animal care, breeding and genotyping.
NR 68
TC 36
Z9 36
U1 3
U2 31
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5110
J9 FRONT NEURAL CIRCUIT
JI Front. Neural Circuits
PD FEB 19
PY 2013
VL 7
AR 22
DI 10.3389/fncir.2013.00022
PG 20
WC Neurosciences
SC Neurosciences & Neurology
GA 125SM
UT WOS:000317561600001
PM 23423476
ER
PT J
AU Felix, AS
Cook, LS
Gaudet, MM
Rohan, TE
Schouten, LJ
Setiawan, VW
Wise, LA
Anderson, KE
Bernstein, L
De Vivo, I
Friedenreich, CM
Gapstur, SM
Goldbohm, RA
Henderson, B
Horn-Ross, PL
Kolonel, L
Lacey, JV
Liang, X
Lissowska, J
Magliocco, A
McCullough, ML
Miller, AB
Olson, SH
Palmer, JR
Park, Y
Patel, AV
Prescott, J
Rastogi, R
Robien, K
Rosenberg, L
Schairer, C
Shu, XO
van den Brandt, PA
Virkus, RA
Wentzensen, N
Xiang, YB
Xu, WH
Yang, HP
Brinton, LA
AF Felix, A. S.
Cook, L. S.
Gaudet, M. M.
Rohan, T. E.
Schouten, L. J.
Setiawan, V. W.
Wise, L. A.
Anderson, K. E.
Bernstein, L.
De Vivo, I.
Friedenreich, C. M.
Gapstur, S. M.
Goldbohm, R. A.
Henderson, B.
Horn-Ross, P. L.
Kolonel, L.
Lacey, J. V.
Liang, X.
Lissowska, J.
Magliocco, A.
McCullough, M. L.
Miller, A. B.
Olson, S. H.
Palmer, J. R.
Park, Y.
Patel, A. V.
Prescott, J.
Rastogi, R.
Robien, K.
Rosenberg, L.
Schairer, C.
Shu, X. Ou
van den Brandt, P. A.
Virkus, R. A.
Wentzensen, N.
Xiang, Y-B
Xu, W-H
Yang, H. P.
Brinton, L. A.
TI The etiology of uterine sarcomas: a pooled analysis of the epidemiology
of endometrial cancer consortium
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE risk factors; uterine sarcoma; pooled analysis; obesity; diabetes
ID HISTOLOGIC TYPES; STROMAL SARCOMA; RISK; TUMORS; UTERUS; MARKERS;
OBESITY; OVARIAN; CORPUS
AB Background: Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes.
Methods: We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28 829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma.
Results: Significant risk factors for uterine sarcoma included obesity (body mass index (BMI) >= 30 vs BMI < 25 kg m(-2) (OR: 1.73, 95% CI: 1.22-2.46), P-trend = 0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41-3.83). Older age at menarche was inversely associated with uterine sarcoma risk (>= 15 years vs < 11 years (OR: 0.70, 95% CI: 0.34-1.44), P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82-3.26) or MMMTs (OR: 2.25, 95% Cl: 1.60-3.15, P-heterogeneity = 0.01).
Conclusion: In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age- and race-specific incidence rates for uterine sarcoma are needed.
C1 [Felix, A. S.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Rockville, MD USA.
[Felix, A. S.; Park, Y.; Schairer, C.; Wentzensen, N.; Yang, H. P.; Brinton, L. A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Cook, L. S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA.
[Gaudet, M. M.; Gapstur, S. M.; McCullough, M. L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Rohan, T. E.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Schouten, L. J.; van den Brandt, P. A.] Maastricht Univ, GROW Sch Oncol & Dev Biol, Maastricht, Netherlands.
[Setiawan, V. W.; Henderson, B.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Wise, L. A.; Palmer, J. R.; Rosenberg, L.; Virkus, R. A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
[Anderson, K. E.; Robien, K.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Bernstein, L.; Lacey, J. V.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA.
[De Vivo, I.; Prescott, J.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[De Vivo, I.; Prescott, J.] Harvard Univ, Sch Med, Boston, MA USA.
[De Vivo, I.; Prescott, J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Friedenreich, C. M.] Alberta Hlth Serv Canc Care, Div Canc Care, Edmonton, AB, Canada.
[Goldbohm, R. A.] Netherlands Org Appl Sci Res TNO, Dept Prevent & Hlth, Leiden, Netherlands.
[Horn-Ross, P. L.] Canc Prevent Inst Calif, Fremont, CA USA.
[Kolonel, L.] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA.
[Liang, X.; Olson, S. H.; Rastogi, R.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Lissowska, J.] M Sklodowska Curie Mem Canc Ctr & Inst Oncol, Warsaw, Poland.
[Magliocco, A.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Anat Pathol, Tampa, FL 33682 USA.
[Miller, A. B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Shu, X. Ou] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
[Xiang, Y-B; Xu, W-H] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
RP Felix, AS (reprint author), NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Rockville, MD USA.
EM ashley.felix@nih.gov
RI Schouten, Leo/G-3713-2012; Brinton, Louise/G-7486-2015; Felix,
Ashley/A-3240-2016;
OI Brinton, Louise/0000-0003-3853-8562; Palmer, Julie/0000-0002-6534-335X;
Lissowska, Jolanta/0000-0003-2695-5799; Wise,
Lauren/0000-0003-2138-3752; Robien, Kim/0000-0002-2120-2280; Park,
Yikyung/0000-0002-6281-489X
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health.
NR 28
TC 11
Z9 14
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 FEB 19
PY 2013
VL 108
IS 3
BP 727
EP 734
DI 10.1038/bjc.2013.2
PG 8
WC Oncology
SC Oncology
GA 111LS
UT WOS:000316523400035
PM 23348519
ER
PT J
AU Zarelli, VE
Dawid, IB
AF Zarelli, Valeria E.
Dawid, Igor B.
TI Inhibition of neural crest formation by Kctd15 involves regulation of
transcription factor AP-2
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE neural plate border; Tfap2; FoxD3; transcriptional regulation
ID CRANIOFACIAL DEVELOPMENT; SIGNALING PATHWAYS; XENOPUS EMBRYOS;
BINDING-SITES; PLATE BORDER; BTB DOMAIN; EXPRESSION; GENE; INDUCTION;
ZEBRAFISH
AB The neural crest develops in vertebrate embryos within a discrete domain at the neural plate boundary and eventually gives rise to a migrating population of cells that differentiate into a multitude of derivatives. We have shown that the broad-complex, tramtrack and bric a brac (BTB) domain-containing factor potassium channel tetramerization domain containing 15 (Kctd15) inhibits neural crest formation, and we proposed that its function is to delimit the neural crest domain. Here we report that Kctd15 is a highly effective inhibitor of transcription factor activating enhancer binding protein 2 (AP-2) in zebrafish embryos and in human cells; AP-2 is known to be critical for several steps of neural crest development. Kctd15 interacts with AP-2 alpha but does not interfere with its nuclear localization or binding to cognate sites in the genome. Kctd15 binds specifically to the activation domain of AP-2 alpha and efficiently inhibits transcriptional activation by a hybrid protein composed of the regulatory protein Gal4 DNA binding and AP-2 alpha activation domains. Mutation of one proline residue in the activation domain to an alanine (P59A) yields a protein that is highly active but largely insensitive to Kctd15. These results indicate that Kctd15 acts in the embryo at least in part by specifically binding to the activation domain of AP-2 alpha, thereby blocking the function of this critical factor in the neural crest induction hierarchy.
C1 [Zarelli, Valeria E.; Dawid, Igor B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
RP Dawid, IB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM idawid@nih.gov
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development
FX We thank Martha Rebbert for assistance with Xenopus experiments, and
Sunit Dutta, Ramanujan Hegde, Helen Hurst, Javier Magadan, Hyunju Ro,
Tom Sargent, Trevor Williams, and Minho Won for advice and reagents.
This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development.
NR 63
TC 17
Z9 24
U1 0
U2 5
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 FEB 19
PY 2013
VL 110
IS 8
BP 2870
EP 2875
DI 10.1073/pnas.1300203110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 103YC
UT WOS:000315954400058
PM 23382213
ER
PT J
AU Gostissa, M
Bianco, JM
Malkin, DJ
Kutok, JL
Rodig, SJ
Morse, HC
Bassing, CH
Alt, FW
AF Gostissa, Monica
Bianco, Julia M.
Malkin, Daniel J.
Kutok, Jeffery L.
Rodig, Scott J.
Morse, Herbert C., III
Bassing, Craig H.
Alt, Frederick W.
TI Conditional inactivation of p53 in mature B cells promotes generation of
nongerminal center-derived B-cell lymphomas
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID MARGINAL ZONE LYMPHOMA; CHROMOSOMAL TRANSLOCATIONS; SOMATIC
HYPERMUTATION; ONCOGENIC TRANSLOCATIONS; GENOMIC INSTABILITY;
P53-DEFICIENT MICE; BREAST-CANCER; HISTONE H2AX; MOUSE MODEL; DNA BREAKS
AB The p53 tumor suppressor exerts a central role in protecting cells from oncogenic transformation. Accordingly, the p53 gene is mutated in a large number of human cancers. In mice, germ-line inactivation of p53 confers strong predisposition to development of different types of malignancies, but the early onset of thymic lymphomas in the majority of the animals prevents detailed studies of tumorigenesis in other tissues. Here, we use the Cre/Lox approach to inactivate p53 in mature B cells in mice (referred to as "CP" B cells) and find that such p53 inactivation results in the routine development of IgM-positive CP peripheral B-cell lymphomas. The CP lymphomas generally appear to arise, even in mice subjected to immunization protocols to activate germinal center reaction, from naive B cells that had not undergone immunoglobulin (Ig) heavy chain gene class switching or somatic hypermutation. In contrast to thymic lymphomas that arise in p53-deficient mice, which generally lack clonal translocations, nearly all analyzed CP B-cell tumors carried clonal translocations. However, in contrast to spontaneous translocations in other mouse B-cell tumor models, CP B-cell tumor translocations were not recurrent and did not involve Ig loci. Therefore, CP tumors might provide models for human lymphomas lacking Ig translocations, such as splenic marginal zone B-cell lymphoma or Waldenstrom macroglobulinemia. Our studies indicate that deletion of p53 is sufficient to trigger transformation of mature B cells and support the notion that p53 deficiency may allow accumulation of oncogenic translocations in B cells.
C1 [Gostissa, Monica; Bianco, Julia M.; Malkin, Daniel J.; Alt, Frederick W.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston Childrens Hosp, Boston, MA 02115 USA.
[Gostissa, Monica; Bianco, Julia M.; Malkin, Daniel J.; Alt, Frederick W.] Harvard Univ, Sch Med, Program Cellular & Mol Med, Boston Childrens Hosp, Boston, MA 02115 USA.
[Gostissa, Monica; Bianco, Julia M.; Malkin, Daniel J.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Kutok, Jeffery L.; Rodig, Scott J.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Morse, Herbert C., III] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Bassing, Craig H.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston Childrens Hosp, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu
OI Morse, Herbert/0000-0002-9331-3705
FU National Institutes of Health [5P01CA92625, CA098285]; Leukemia and
Lymphoma Society of America (LLS) Specialized Center of Research grant;
Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases
FX We thank Roberto Chiarle for helpful suggestions. This work was
supported by National Institutes of Health Grants 5P01CA92625 and
CA098285 and a Leukemia and Lymphoma Society of America (LLS)
Specialized Center of Research grant (to F. W. A.). This work was
supported in part by the Intramural Research Program of the National
Institutes of Health, National Institute of Allergy and Infectious
Diseases (to H. C. M.). M. G. was an LLS senior fellow. C. H. B. is an
LLS Scholar. F. W. A. is an investigator of the Howard Hughes Medical
Institute.
NR 48
TC 11
Z9 11
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 FEB 19
PY 2013
VL 110
IS 8
BP 2934
EP 2939
DI 10.1073/pnas.1222570110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 103YC
UT WOS:000315954400069
PM 23382223
ER
PT J
AU Baccala, R
Gonzalez-Quintial, R
Blasius, AL
Rimann, I
Ozato, K
Kono, DH
Beutler, B
Theofilopoulos, AN
AF Baccala, Roberto
Gonzalez-Quintial, Rosana
Blasius, Amanda L.
Rimann, Ivo
Ozato, Keiko
Kono, Dwight H.
Beutler, Bruce
Theofilopoulos, Argyrios N.
TI Essential requirement for IRF8 and SLC15A4 implicates plasmacytoid
dendritic cells in the pathogenesis of lupus
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID I INTERFERON INDUCTION; APOPTOTIC U937 CELLS; TOLL-LIKE RECEPTORS;
ACTIVATE B-CELLS; NUCLEIC-ACID; SYSTEMIC AUTOIMMUNITY;
RHEUMATOID-ARTHRITIS; SUSCEPTIBILITY LOCI; IMMUNE-COMPLEXES; ALPHA
PRODUCTION
AB In vitro evidence suggests that plasmacytoid dendritic cells (pDCs) are intimately involved in the pathogenesis of lupus. However, it remains to be determined whether these cells are required in vivo for disease development, and whether their contribution is restricted to hyperproduction of type I IFNs. To address these issues, we created lupus-predisposed mice lacking the IFN regulatory factor 8 (IRF8) or carrying a mutation that impairs the peptide/histidine transporter solute carrier family 15, member 4 (SLC15A4). IRF8-deficient NZB mice, lacking pDCs, showed almost complete absence of anti-nuclear, anti-chromatin, and anti-erythrocyte autoantibodies, along with reduced kidney disease. These effects were observed despite normal B-cell responses to Toll-like receptor (TLR) 7 and TLR9 stimuli and intact humoral responses to conventional T-dependent and -independent antigens. Moreover, Slc15a4 mutant C57BL/6-Fas(lpr) mice, in which pDCs are present but unable to produce type I IFNs in response to endosomal TLR ligands, also showed an absence of autoantibodies, reduced lymphadenopathy and splenomegaly, and extended survival. Taken together, our results demonstrate that pDCs and the production of type I IFNs by these cells are critical contributors to the pathogenesis of lupus-like autoimmunity in these models. Thus, IRF8 and SLC15A4 may provide important targets for therapeutic intervention in human lupus.
C1 [Baccala, Roberto; Gonzalez-Quintial, Rosana; Rimann, Ivo; Kono, Dwight H.; Theofilopoulos, Argyrios N.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Blasius, Amanda L.; Beutler, Bruce] Scripps Res Inst, Dept Genet, La Jolla, CA 92037 USA.
[Ozato, Keiko] NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Beutler, Bruce] Univ Texas SW Med Ctr Dallas, Ctr Genet Host Def, Dallas, TX 75390 USA.
RP Baccala, R (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
EM rbaccala@scripps.edu; Bruce.Beutler@UTSouthwestern.edu;
argyrio@scripps.edu
FU National Institutes of Health [AR53228, AR31203, AR39555,
1U19-AI100627-01, 2P01-AI070167-06A1]; Irvington Institute Fellowship
Program of the Cancer Research Institute
FX We thank Carrie N. Arnold for assistance with the B cell proliferation
assays and Anthony Nguyen for excellent technical support. This work was
supported by National Institutes of Health Grants AR53228, AR31203,
AR39555, 1U19-AI100627-01, and 2P01-AI070167-06A1. A. L. B. was
supported by The Irvington Institute Fellowship Program of the Cancer
Research Institute. This is article number 22092 from The Scripps
Research Institute, Department of Immunology and Microbial Sciences.
NR 68
TC 37
Z9 37
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 FEB 19
PY 2013
VL 110
IS 8
BP 2940
EP 2945
DI 10.1073/pnas.1222798110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 103YC
UT WOS:000315954400070
PM 23382217
ER
PT J
AU Patel, V
Jalah, R
Kulkarni, V
Valentin, A
Rosati, M
Alicea, C
von Gegerfelt, A
Huang, WS
Guan, YJ
Keele, BF
Bess, JW
Piatak, M
Lifson, JD
Williams, WT
Shen, XY
Tomaras, GD
Amara, RR
Robinson, HL
Johnson, W
Broderick, KE
Sardesai, NY
Venzon, DJ
Hirsch, VM
Felber, BK
Pavlakis, GN
AF Patel, Vainav
Jalah, Rashmi
Kulkarni, Viraj
Valentin, Antonio
Rosati, Margherita
Alicea, Candido
von Gegerfelt, Agneta
Huang, Wensheng
Guan, Yongjun
Keele, Brandon F.
Bess, Julian W., Jr.
Piatak, Michael, Jr.
Lifson, Jeffrey D.
Williams, William T.
Shen, Xiaoying
Tomaras, Georgia D.
Amara, Rama R.
Robinson, Harriet L.
Johnson, Welkin
Broderick, Kate E.
Sardesai, Niranjan Y.
Venzon, David J.
Hirsch, Vanessa M.
Felber, Barbara K.
Pavlakis, George N.
TI DNA and virus particle vaccination protects against acquisition and
confers control of viremia upon heterologous simian immunodeficiency
virus challenge
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE virus acquisition; HIV-1 vaccine; viral vaccines/immunology; humoral
immunity; HIV-1/immunology
ID RHESUS MACAQUES; IMMUNE-RESPONSES; HIV-1 INFECTION; SIVMAC251 CHALLENGE;
T-CELLS; SIV; SIVSME660; EFFICACY; VACCINES; MONKEYS
AB We have previously shown that macaques vaccinated with DNA vectors expressing SIVmac239 antigens developed potent immune responses able to reduce viremia upon high-dose SIVmac251 challenge. To further improve vaccine-induced immunity and protection, we combined the SIVmac239 DNA vaccine with protein immunization using inactivated SIVmac239 viral particles as protein source. Twenty-six weeks after the last vaccination, the animals were challenged intrarectally at weekly intervals with a titrated dose of the heterologous SIVsmE660. Two of DNA-protein coimmunized macaques did not become infected after 14 challenges, but all controls were infected by 11 challenges. Vaccinated macaques showed modest protection from SIVsmE660 acquisition compared with naive controls (P = 0.050; stratified for TRIM5 alpha genotype). Vaccinees had significantly lower peak (1.6 log, P = 0.0048) and chronic phase viremia (P = 0.044), with 73% of the vaccinees suppressing viral replication to levels below assay detection during the 40-wk follow-up. Vaccine-induced immune responses associated significantly with virus control: binding antibody titers and the presence of rectal IgG to SIVsmE660 Env correlated with delayed SIVsmE660 acquisition; SIV-specific cytotoxic T cells, prechallenge CD4(+) effector memory, and postchallenge CD8(+) transitional memory cells correlated with control of viremia. Thus, SIVmac239 DNA and protein-based vaccine protocols were able to achieve high, persistent, broad, and effective cellular and humoral immune responses able to delay heterologous SIVsmE660 infection and to provide long-term control of viremia. These studies support a role of DNA and protein-based vaccines for development of an efficacious HIV/AIDS vaccine.
C1 [Patel, Vainav; Valentin, Antonio; Rosati, Margherita; von Gegerfelt, Agneta; Pavlakis, George N.] Frederick Natl Lab Canc Res, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA.
[Jalah, Rashmi; Kulkarni, Viraj; Alicea, Candido; Felber, Barbara K.] Frederick Natl Lab Canc Res, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA.
[Huang, Wensheng; Guan, Yongjun] Univ Maryland, Sch Med, Inst Human Virol, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Keele, Brandon F.; Bess, Julian W., Jr.; Piatak, Michael, Jr.; Lifson, Jeffrey D.] Sci Applicat Int Corp Frederick Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Williams, William T.; Shen, Xiaoying; Tomaras, Georgia D.] Duke Human Vaccine Inst, Durham, NC 27710 USA.
[Amara, Rama R.] Emory Univ, Yerkes Natl Primate Ctr, Atlanta, GA 30329 USA.
[Robinson, Harriet L.] GeoVax Inc, Smyrna, GA 30080 USA.
[Johnson, Welkin] Boston Coll, Dept Biol, Boston, MA 02467 USA.
[Broderick, Kate E.; Sardesai, Niranjan Y.] Inovio Pharmaceut Inc, Blue Bell, PA 19422 USA.
[Venzon, David J.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20852 USA.
[Hirsch, Vanessa M.] NIAID, Nonhuman Primate Virol Sect, Mol Microbiol Lab, Bethesda, MD 20814 USA.
RP Felber, BK (reprint author), Frederick Natl Lab Canc Res, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA.
EM felberb@mail.nih.gov; pavlakig@mail.nih.gov
RI Tomaras, Georgia/J-5041-2016; bebarta, vikhyat/K-3476-2015
FU National Cancer Institute, National Institutes of Health (NCI/NIH)
[HHSN261200800001E]; NIH [AI083118]; National Institute of Allergy and
Infectious Diseases-NIH [HHSN27201100016C]
FX We thank D. Weiss, J. Treece, E. M. Lee, I. Kalisz, and the staff at
Advanced BioScience Laboratory; C. LaBranche and D. C. Montefiori for
the Nab assay; Glenn Overman for the mucosal binding antibody assays; B.
Chowdhury, T. Ireland, B. Bohn, and J. Miller for technical assistance;
and T. Jones for editorial assistance. This work was supported in part
by the Intramural Research Program of the National Cancer Institute,
National Institutes of Health (NCI/NIH) (B. K. F. and G. N. P.); federal
funds from the NCI/NIH under Contract HHSN261200800001E (to J. D. L.);
NIH Grant AI083118 (to W. J.); and National Institute of Allergy and
Infectious Diseases-NIH Contract HHSN27201100016C (to G. D. T., X. S.,
C. LaBranche, and D. C. Montefiori).
NR 31
TC 40
Z9 40
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 FEB 19
PY 2013
VL 110
IS 8
BP 2975
EP 2980
DI 10.1073/pnas.1215393110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 103YC
UT WOS:000315954400076
PM 23359688
ER
PT J
AU Wang, DR
El-Amouri, SS
Dai, M
Kuan, CY
Hui, DY
Brady, RO
Pan, D
AF Wang, Daren
El-Amouri, Salim S.
Dai, Mei
Kuan, Chia-Yi
Hui, David Y.
Brady, Roscoe O.
Pan, Dao
TI Engineering a lysosomal enzyme with a derivative of receptor-binding
domain of apoE enables delivery across the blood-brain barrier
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE in vivo evaluation; LDL receptor-related protein 1; lysosomal storage
diseases; neurological disorders; CNS protein delivery
ID MUCOPOLYSACCHARIDOSIS TYPE-I; APOLIPOPROTEIN-E; HURLER-SYNDROME;
GENE-THERAPY; REPLACEMENT THERAPY; ALZHEIMERS-DISEASE; TARGETED
DELIVERY; FUSION PROTEIN; DRUG-DELIVERY; BONE-MARROW
AB To realize the potential of large molecular weight substances to treat neurological disorders, novel approaches are required to surmount the blood-brain barrier (BBB). We investigated whether fusion of a receptor-binding peptide from apolipoprotein E (apoE) with a potentially therapeutic protein can bind to LDL receptors on the BBB and be transcytosed into the CNS. A lysosomal enzyme, alpha-L-iduronidase (IDUA), was used for biological and therapeutic evaluation in a mouse model of mucopolysaccharidosis (MPS) type I, one of the most common lysosomal storage disorders with CNS deficits. We identified two fusion candidates, IDUAe1 and IDUAe2, by in vitro screening, that exhibited desirable receptor-mediated binding, endocytosis, and transendothelial transport as well as appropriate lysosomal enzyme trafficking and biological function. Robust peripheral IDUAe1 or IDUAe2 generated by transient hepatic expression led to elevated enzyme levels in capillary-depleted, enzyme-deficient brain tissues and protein delivery into nonendothelium perivascular cells, neurons, and astrocytes within 2 d of treatment. Moreover, 5 mo after long-term delivery of moderate levels of IDUAe1 derived from maturing red blood cells, 2% to 3% of normal brain IDUA activities were obtained in MPS I mice, and IDUAe1 protein was detected in neurons and astrocytes throughout the brain. The therapeutic potential was demonstrated by normalization of brain glycosaminoglycan and beta-hexosaminidase in MPS I mice 5 mo after moderate yet sustained delivery of IDUAe1. These findings provide a noninvasive and BBB-targeted procedure for the delivery of large-molecule therapeutic agents to treat neurological lysosomal storage disorders and potentially other diseases that involve the brain.
C1 [Wang, Daren; El-Amouri, Salim S.; Dai, Mei; Pan, Dao] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
[Kuan, Chia-Yi] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH 45229 USA.
[Hui, David Y.] Univ Cincinnati, Dept Pathol, Cincinnati, OH 45267 USA.
[Pan, Dao] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45267 USA.
[Brady, Roscoe O.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
RP Brady, RO (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
EM bradyr@ninds.nih.gov; dao.pan@cchmc.org
FU National Institutes of Health [NS064330, DK074932, U54 HL06-008]
FX We thank Meghan Bromwell and the Comprehensive Mouse Core for technical
assistance. We thank Dr. C. Miao (Seattle Children's Research Institute)
for the pBS-HCRHPI-A plasmid and Dr. M. Krieger (Massachusetts Institute
of Technology) for the CHOLDLRneg cell line. This work was
supported by the National Institutes of Health Grants NS064330,
DK074932, and U54 HL06-008.
NR 37
TC 27
Z9 27
U1 0
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 FEB 19
PY 2013
VL 110
IS 8
BP 2999
EP 3004
DI 10.1073/pnas.1222742110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 103YC
UT WOS:000315954400080
PM 23382178
ER
PT J
AU Arnold, ES
Ling, SC
Huelga, SC
Lagier-Tourenne, C
Polymenidou, M
Ditsworth, D
Kordasiewicz, HB
McAlonis-Downes, M
Platoshyn, O
Parone, PA
Da Cruz, S
Clutario, KM
Swing, D
Tessarollo, L
Marsala, M
Shaw, CE
Yeo, GW
Cleveland, DW
AF Arnold, Eveline S.
Ling, Shuo-Chien
Huelga, Stephanie C.
Lagier-Tourenne, Clotilde
Polymenidou, Magdalini
Ditsworth, Dara
Kordasiewicz, Holly B.
McAlonis-Downes, Melissa
Platoshyn, Oleksandr
Parone, Philippe A.
Da Cruz, Sandrine
Clutario, Kevin M.
Swing, Debbie
Tessarollo, Lino
Marsala, Martin
Shaw, Christopher E.
Yeo, Gene W.
Cleveland, Don W.
TI ALS-linked TDP-43 mutations produce aberrant RNA splicing and
adult-onset motor neuron disease without aggregation or loss of nuclear
TDP-43
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE neurodegeneration; RNA binding proteins; frontotemporal dementia
ID AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION;
DNA-BINDING PROTEIN-43; TRANSGENIC MICE; SPINAL-CORD; PROCESSING
PROTEIN; CELLULAR TOXICITY; TARDBP MUTATIONS; ALPHA-SYNUCLEIN; MUTANT
TDP-43
AB Transactivating response region DNA binding protein (TDP-43) is the major protein component of ubiquitinated inclusions found in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions. Two ALS-causing mutants (TDP-43(Q331K) and TDP-43(M337V)), but not wild-type human TDP-43, are shown here to provoke age-dependent, mutant-dependent, progressive motor axon degeneration and motor neuron death when expressed in mice at levels and in a cell type-selective pattern similar to endogenous TDP-43. Mutant TDP-43-dependent degeneration of lower motor neurons occurs without: (i) loss of TDP-43 from the corresponding nuclei, (ii) accumulation of TDP-43 aggregates, and (iii) accumulation of insoluble TDP-43. Computational analysis using splicing-sensitive microarrays demonstrates alterations of endogenous TDP-43-dependent alternative splicing events conferred by both human wild-type and mutant TDP-43(Q331K), but with high levels of mutant TDP-43 preferentially enhancing exon exclusion of some target pre-mRNAs affecting genes involved in neurological transmission and function. Comparison with splicing alterations following TDP-43 depletion demonstrates that TDP-43(Q331K) enhances normal TDP-43 splicing function for some RNA targets but loss-of-function for others. Thus, adult-onset motor neuron disease does not require aggregation or loss of nuclear TDP-43, with ALS-linked mutants producing loss and gain of splicing function of selected RNA targets at an early disease stage.
C1 [Ling, Shuo-Chien; Cleveland, Don W.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Arnold, Eveline S.; Ling, Shuo-Chien; Huelga, Stephanie C.; Lagier-Tourenne, Clotilde; Polymenidou, Magdalini; Ditsworth, Dara; Kordasiewicz, Holly B.; McAlonis-Downes, Melissa; Parone, Philippe A.; Da Cruz, Sandrine; Clutario, Kevin M.; Yeo, Gene W.; Cleveland, Don W.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
[Platoshyn, Oleksandr; Marsala, Martin] Univ Calif San Diego, Dept Anesthesiol, La Jolla, CA 92093 USA.
[Arnold, Eveline S.; Ling, Shuo-Chien; Lagier-Tourenne, Clotilde; Polymenidou, Magdalini; Ditsworth, Dara; Kordasiewicz, Holly B.; McAlonis-Downes, Melissa; Parone, Philippe A.; Da Cruz, Sandrine; Clutario, Kevin M.; Cleveland, Don W.] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
[Huelga, Stephanie C.; Platoshyn, Oleksandr; Marsala, Martin; Yeo, Gene W.] Univ Calif San Diego, Stem Cell Program, La Jolla, CA 92093 USA.
[Huelga, Stephanie C.; Platoshyn, Oleksandr; Marsala, Martin; Yeo, Gene W.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.
[Swing, Debbie; Tessarollo, Lino] NCI, Neural Dev Sect, Mouse Canc Genet Program, Frederick, MD 21702 USA.
[Shaw, Christopher E.] Kings Coll London, Inst Psychiat, MRC, Ctr Neurodegenerat Res, London SE5 8AF, England.
RP Cleveland, DW (reprint author), Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
EM dcleveland@ucsd.edu
FU Wellcome Trust; Ludwig Institute for Cancer Research; University of
California San Diego Genetics Training Grant National Institute of
General Medical Sciences [T32 GM008666]; National Institutes of Health
Neuroplasticity of Aging Training Grant [T32 AG 000216]; National
Science Foundation Graduate Research Fellowship; Amyotrophic Lateral
Sclerosis Association; Muscular Dystrophy Association Career Development
Award; National Institutes of Health [NS075449, HG004659, NS075216];
[NS069144]
FX The authors thank Timothy Meerloo and Ying Jones (University of
California at San Diego) and Janet Folmer (The Johns Hopkins University)
for technical assistance in plastic thin sectioning and staining; Seiya
Tokunaga, Sandra Lee, Anne Vetto, and Han Jin Park for technical
assistance; and all members of the D. W. C. laboratory for helpful
suggestions and discussion regarding the work. This work was supported
by a Wellcome Trust grant (to D. W. C. and C. E. S.) and Grant NS069144
(to D. W. C.); salary support from the Ludwig Institute for Cancer
Research (D. W. C.); University of California San Diego Genetics
Training Grant National Institute of General Medical Sciences T32
GM008666 (to E. S. A.); National Institutes of Health Neuroplasticity of
Aging Training Grant T32 AG 000216 (to S.-C. L.); a National Science
Foundation Graduate Research Fellowship (to S. C. H.); a Milton
Safenowitz Postdoctoral Fellowship from the Amyotrophic Lateral
Sclerosis Association (to D. D.); a Muscular Dystrophy Association
Career Development Award (to C. L.-T.); and National Institutes of
Health Grants NS075449 and HG004659 (to G. W. Y.) and NS075216 (to M.
P.). G. W. Y. is an Alfred P. Sloan Research Fellow.
NR 63
TC 80
Z9 83
U1 3
U2 33
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 FEB 19
PY 2013
VL 110
IS 8
BP E736
EP E745
DI 10.1073/pnas.1222809110
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 103YC
UT WOS:000315954400016
PM 23382207
ER
PT J
AU Frisz, JF
Lou, KY
Klitzing, HA
Hanafin, WP
Lizunov, V
Wilson, RL
Carpenter, KJ
Kim, R
Hutcheon, ID
Zimmerberg, J
Weber, PK
Kraft, ML
AF Frisz, Jessica F.
Lou, Kaiyan
Klitzing, Haley A.
Hanafin, William P.
Lizunov, Vladimir
Wilson, Robert L.
Carpenter, Kevin J.
Kim, Raehyun
Hutcheon, Ian D.
Zimmerberg, Joshua
Weber, Peter K.
Kraft, Mary L.
TI Direct chemical evidence for sphingolipid domains in the plasma
membranes of fibroblasts
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE SIMS; stable isotope
ID ION MASS-SPECTROMETRY; GPI-ANCHORED PROTEINS; CELL-MEMBRANE; LIPID
RAFTS; INFLUENZA-VIRUS; CHOLESTEROL; SURFACE; ACTIN; ORGANIZATION;
MOLECULES
AB Sphingolipids play important roles in plasma membrane structure and cell signaling. However, their lateral distribution in the plasma membrane is poorly understood. Here we quantitatively analyzed the sphingolipid organization on the entire dorsal surface of intact cells by mapping the distribution of N-15-enriched ions from metabolically labeled N-15-sphingolipids in the plasma membrane, using high-resolution imaging mass spectrometry. Many types of control experiments (internal, positive, negative, and fixation temperature), along with parallel experiments involving the imaging of fluorescent sphingolipids-both in living cells and during fixation of living cells-exclude potential artifacts. Micrometer-scale sphingolipid patches consisting of numerous N-15-sphingolipid microdomains with mean diameters of similar to 200 nm are always present in the plasma membrane. Depletion of 30% of the cellular cholesterol did not eliminate the sphingolipid domains, but did reduce their abundance and long-range organization in the plasma membrane. In contrast, disruption of the cytoskeleton eliminated the sphingolipid domains. These results indicate that these sphingolipid assemblages are not lipid rafts and are instead a distinctly different type of sphingolipid-enriched plasma membrane domain that depends upon cortical actin.
C1 [Frisz, Jessica F.; Lou, Kaiyan; Klitzing, Haley A.; Hanafin, William P.; Wilson, Robert L.; Kim, Raehyun; Kraft, Mary L.] Univ Illinois, Sch Chem Sci, Urbana, IL 61801 USA.
[Lizunov, Vladimir; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Carpenter, Kevin J.; Hutcheon, Ian D.; Weber, Peter K.] Lawrence Livermore Natl Lab, Glenn T Seaborg Inst, Livermore, CA 94551 USA.
RP Kraft, ML (reprint author), Univ Illinois, Sch Chem Sci, Urbana, IL 61801 USA.
EM mlkraft@illinois.edu
RI Lou, Kaiyan/D-4199-2012; Wunder, Stephanie/B-5066-2012; Zdilla,
Michael/B-4145-2011
OI Lou, Kaiyan/0000-0003-3443-0343;
FU US Department of Energy [DE-FG02-07ER46471]; Burroughs Wellcome Fund;
National Institutes of Health [T32 GM070421]; Laboratory Directed
Research and Development funding; National Institute of Child Health and
Human Development; National Institutes of Health; National Science
Foundation [CHE-1058809]
FX We thank C. Ramon for technical assistance and L. R. Nittler for
software development. Portions of this work were carried out in the
Metabolomics Center in the Roy J. Carver Biotechnology Center,
University of Illinois and the Frederick Seitz Materials Research
Laboratory Central Facilities, University of Illinois, which is
partially supported by the US Department of Energy under Grant
DE-FG02-07ER46471. M. L. K. holds a Career Award at the Scientific
Interface from the Burroughs Wellcome Fund. J. F. F. was supported by
the National Institutes of Health Training Program in the
Chemistry-Biology Interface (T32 GM070421). Work at Lawrence Livermore
National Laboratory was supported by Laboratory Directed Research and
Development funding and performed under the auspices of the US
Department of Energy under Contract DE-AC52-07NA27344. This work was
partially supported by the Intramural Program of the National Institute
of Child Health and Human Development; National Institutes of Health;
and by the National Science Foundation under Grant CHE-1058809.
NR 52
TC 60
Z9 60
U1 3
U2 59
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 FEB 19
PY 2013
VL 110
IS 8
BP E613
EP E622
DI 10.1073/pnas.1216585110
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 103YC
UT WOS:000315954400003
PM 23359681
ER
PT J
AU Ng, KY
Chew, KK
Kaur, P
Kwan, JY
Khong, WX
Lin, L
Chua, A
Tan, MT
Quinn, TC
Laeyendecker, O
Leo, YS
Ng, OT
AF Ng, Kah Ying
Chew, Kuan Kiat
Kaur, Palvinder
Kwan, Joe Yap
Khong, Wei Xin
Lin, Li
Chua, Arlene
Tan, Mei Ting
Quinn, Thomas C.
Laeyendecker, Oliver
Leo, Yee Sin
Ng, Oon Tek
TI High prevalence of CXCR4 usage among treatment-naive CRF01_AE and
CRF51_01B-infected HIV-1 subjects in Singapore
SO BMC INFECTIOUS DISEASES
LA English
DT Article
DE CXCR4 usage; HIV-1; treatment-naive
ID SYNCYTIUM-INDUCING PHENOTYPE; CORECEPTOR USAGE; VIRAL TROPISM;
PREDICTION; SUBTYPES; TOOLS
AB Background: Recent studies suggest HIV-1 inter-subtype differences in co-receptor usage. We examined the correlation between HIV-1 subtype and co-receptor usage among treatment-naive HIV-1 subjects in Singapore. Additionally, we investigated whether the subtype co-receptor association was influenced by stage of infection.
Methods: V3 sequences of HIV-1 envelope protein gp120 were obtained from 110 HIV treatment-naive patients and genotypic co-receptor tropism determination was performed using Geno2pheno. Two false-positive rate (FPR) cut-offs, 10% and 5.75% were selected for tropism testing.
Results: Subtype assignment of viral strains from 110 HIV-infected individuals based on partial sequencing of HIV-1 pol, gp120 and gp41 were as follows: 27 subtype B, 64 CRF01_AE, 10 CRF51_01B, and 9 other subtypes. At FPR=10%, 10 (100%) CRF51_01B-infected subjects and 26 (40.6%) CRF01_AE-infected subjects had CXCR4-using virus, compared to 7 (25.9%) subtype B subjects and 1 (11.1%) CRF33_01B-infected subject (P < 0.001). At FPR=5.75%, 10 (100%) CRF51_01B-infected subjects and 20 (31.3%) CRF01_AE-infected subjects had CXCR4-using virus, compared to 4 (14.8%) subtype B and 1 (11.1%) CRF33_01B-infected subjects (P < 0.001). Among those with evidence of seroconversion within 2 years prior to study enrolment, 100% of CRF51_01B-infected subjects had CXCR4-using virus, independent of Geno2pheno FPR.
Conclusion: CRF51_01B and CRF01_AE-infected individuals have higher prevalence of CXCR4-usage compared to subtype B infected individuals. Further studies examining these differences could help optimise the use of CCR5-antagonist in populations with these subtypes, and increase our understanding of HIV-1 biology.
C1 [Ng, Kah Ying; Chew, Kuan Kiat; Kaur, Palvinder; Kwan, Joe Yap; Khong, Wei Xin; Chua, Arlene; Tan, Mei Ting; Leo, Yee Sin; Ng, Oon Tek] Tan Tock Seng Hosp, Inst Infect Dis & Epidemiol, Communicable Dis Ctr, Singapore 308433, Singapore.
[Lin, Li] Jurong Gen Hosp, Dept Infect Dis, Singapore 159964, Singapore.
[Quinn, Thomas C.; Laeyendecker, Oliver] Johns Hopkins Sch Med, Baltimore, MD USA.
[Quinn, Thomas C.; Laeyendecker, Oliver] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Baltimore, MD USA.
RP Ng, OT (reprint author), Tan Tock Seng Hosp, Inst Infect Dis & Epidemiol, Communicable Dis Ctr, Singapore 308433, Singapore.
EM oon_tek_NG@ttsh.com.sg
RI Laeyendecker, Oliver/B-9331-2009;
OI Laeyendecker, Oliver/0000-0002-6429-4760; Chua,
Arlene/0000-0001-6428-9083
FU A Singapore National Medical Research Training Fellowship; Division of
Intramural Research, NIAID, NIH
FX A Singapore National Medical Research Training Fellowship grant provided
salary support for O.T. Ng. We acknowledge the physicians, staff, and
patients of the outpatient service at the Communicable Disease Centre,
Singapore who made this study possible. Additional support was provided
by the Division of Intramural Research, NIAID, NIH.
NR 19
TC 8
Z9 8
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD FEB 19
PY 2013
VL 13
AR 90
DI 10.1186/1471-2334-13-90
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA 099OA
UT WOS:000315629900001
PM 23421710
ER
PT J
AU Hall, B
Nakashima, H
Sun, ZJ
Sato, Y
Bian, YS
Husain, SR
Puri, RK
Kulkarni, AB
AF Hall, Bradford
Nakashima, Hideyuki
Sun, Zhi-Jun
Sato, Yuki
Bian, Yansong
Husain, Syed R.
Puri, Raj K.
Kulkarni, Ashok B.
TI Targeting of interleukin-13 receptor alpha 2 for treatment of head and
neck squamous cell carcinoma induced by conditional deletion of TGF-beta
and PTEN signaling
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE IL-13 receptor; Immunotoxin; TGF-beta; PTEN; HNSCC
ID POTENT ANTITUMOR-ACTIVITY; CHIMERIC FUSION PROTEINS; MURINE
TUMOR-MODELS; PSEUDOMONAS EXOTOXIN; IL-13 CYTOTOXIN; MOUSE MODEL;
EXPRESSION; CANCER; THERAPY; CHAIN
AB Background: The sixth leading class of cancer worldwide is head and neck cancer, which typically arise within the squamous epithelium of the oral mucosa. Human head and neck squamous cell carcinoma (HNSCC) is known to be difficult to treat and has only a 50% five-year survival rate. With HNSCC, novel therapeutics are needed along with a means of rapidly screening anti-cancer agents in vivo, such as mouse models.
Methods: In order to develop new animal models of cancer to test safety and efficacy of novel therapeutic agents for human HNSCC, tumors resembling clinical cases of human HNSCC were induced in the head and neck epithelium of a genetically engineered mouse model. This mouse model was generated by conditional deletion of two tumor suppressors, Transforming Growth Factor-beta Receptor 1 (TGF beta RI) and Phosphatase and Tensin homolog (PTEN), in the oral epithelium. We discovered that the tumors derived from these Tgfbr1/Pten double conditional knockout (2cKO) mice over-expressed IL-13R alpha 2, a high affinity receptor for IL-13 that can function as a tumor antigen. To demonstrate a proof-of-concept that targeted therapy against IL-13R alpha 2 expression would have any antitumor efficacy in this spontaneous tumor model, these mice were treated systemically with IL-13-PE, a recombinant immunotoxin consisting of IL-13 fused to the Pseudomonas exotoxin A.
Results: Tgfbr1/Pten 2cKO mice when treated with IL-13-PE displayed significantly increased survival when compared to the untreated control mice. The untreated mice exhibited weight loss, particularly with the rapid onset of tongue tumors, but the treated mice gained weight while on IL-13-PE therapy and showed no clinical signs of toxicity due to the immunotoxin. Expression of IL-13Ra2 in tumors was significantly decreased with IL-13-PE treatment as compared to the controls and the number of myeloid-derived suppressor cells (MDSC) was also significantly reduced in the spleens of the IL-13-PE treated mice.
Conclusions: Our study demonstrates that the Tgfbr1/Pten 2cKO mouse model of human HNSCC is a useful model for assessing antitumor activity of new cancer therapeutic agents, and that IL-13-PE has therapeutic potential to treat human head and neck cancer.
C1 [Hall, Bradford; Sun, Zhi-Jun; Bian, Yansong; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
[Nakashima, Hideyuki; Sato, Yuki; Husain, Syed R.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Bian, Yansong] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD USA.
RP Kulkarni, AB (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, 30 Convent Dr,Bldg 30,Room 130, Bethesda, MD USA.
EM ak40m@nih.gov
FU Division of Intramural Research of the National Institute of Dental and
Craniofacial Research, NIH [ZIA-DE-000698]; Center for Biologics
Evaluation and Research, U.S. Food and Drug Administration; National
Institute of Dental and Craniofacial Research; National Institute on
Deafness and Other Communication Disorders, NIH
FX We thank Riddhi Patel for help with the biochemical analysis of tumors,
Alfredo Molinolo for the analysis of the tumor sections, and Shelagh
Johnson for expert editorial assistance. We are grateful to Drs. Jing
Han and Shyh-Ching Lo, CBER, FDA for internal review of the manuscript.
These studies were supported by the Division of Intramural Research of
the National Institute of Dental and Craniofacial Research, NIH to ABK
(ZIA-DE-000698), and the Center for Biologics Evaluation and Research,
U.S. Food and Drug Administration.; Intramural Research Programs of the
National Institute of Dental and Craniofacial Research and National
Institute on Deafness and Other Communication Disorders, NIH, and the
Center for Biologics Evaluation and Research, U.S. Food and Drug
Administration.
NR 31
TC 5
Z9 8
U1 0
U2 6
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 FEB 19
PY 2013
VL 11
AR 45
DI 10.1186/1479-5876-11-45
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 099PL
UT WOS:000315633600002
PM 23421960
ER
PT J
AU Duggal, P
Thio, CL
Wojcik, GL
Goedert, JJ
Mangia, A
Latanich, R
Kim, AY
Lauer, GM
Chung, RT
Peters, MG
Kirk, GD
Mehta, SH
Cox, AL
Khakoo, SI
Alric, L
Cramp, ME
Donfield, SM
Edlin, BR
Tobler, LH
Busch, MP
Alexander, G
Rosen, HR
Gao, XJ
Abdel-Hamid, M
Apps, R
Carrington, M
Thomas, DL
AF Duggal, Priya
Thio, Chloe L.
Wojcik, Genevieve L.
Goedert, James J.
Mangia, Alessandra
Latanich, Rachel
Kim, Arthur Y.
Lauer, Georg M.
Chung, Raymond T.
Peters, Marion G.
Kirk, Gregory D.
Mehta, Shruti H.
Cox, Andrea L.
Khakoo, Salim I.
Alric, Laurent
Cramp, Matthew E.
Donfield, Sharyne M.
Edlin, Brian R.
Tobler, Leslie H.
Busch, Michael P.
Alexander, Graeme
Rosen, Hugo R.
Gao, Xiaojiang
Abdel-Hamid, Mohamed
Apps, Richard
Carrington, Mary
Thomas, David L.
TI Genome-Wide Association Study of Spontaneous Resolution of Hepatitis C
Virus Infection: Data From Multiple Cohorts
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID SPONTANEOUS CLEARANCE; GENETIC-VARIATION; HCV INFECTION; VIRAL LOAD;
HLA; VIREMIA; GENOTYPE; PERSISTENCE; POPULATION; VARIANTS
AB Background: Hepatitis C virus (HCV) infections occur worldwide and either spontaneously resolve or persist and markedly increase the person's lifetime risk for cirrhosis and hepatocellular carcinoma. Although HCV persistence occurs more often in persons of African ancestry and persons with genetic variants near interleukin-28B (IL-28B), the genetic basis is not well-understood.
Objective: To evaluate the host genetic basis for spontaneous resolution of HCV infection.
Design: 2-stage, genome-wide association study.
Setting: 13 international multicenter study sites.
Patients: 919 persons with serum HCV antibodies but no HCV RNA (spontaneous resolution) and 1482 persons with serum HCV antibodies and HCV RNA (persistence).
Measurements: Frequencies of 792 721 single nucleotide polymorphisms (SNPs).
Results: Differences in allele frequencies between persons with spontaneous resolution and persistence were identified on chromosomes 19q13.13 and 6p21.32. On chromosome 19, allele frequency differences localized near IL-28B and included rs12979860 (overall per-allele OR, 0.45; P = 2.17 x 10(-30)) and 10 additional SNPs spanning 55 000 base pairs. On chromosome 6, allele frequency differences localized near genes for HLA class II and included rs4273729 (overall per-allele OR, 0.59; P = 1.71 x 10(-16)) near DQB1*03:01 and an additional 116 SNPs spanning 1 090 000 base pairs. The associations in chromosomes 19 and 6 were independent and additive and explain an estimated 14.9% (95% CI, 8.5% to 22.6%) and 15.8% (CI, 4.4% to 31.0%) of the variation in HCV resolution in persons of European and African ancestry, respectively. Replication of the chromosome 6 SNP, rs4272729, in an additional 745 persons confirmed the findings (P = 0.015).
Limitation: Epigenetic effects were not studied.
Conclusion: IL-28B and HLA class II are independently associated with spontaneous resolution of HCV infection, and SNPs marking IL-28B and DQB1*03:01 may explain approximately 15% of spontaneous resolution of HCV infection.
C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
NCI, Rockville, MD 20852 USA.
IRCCS Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
Ragon Inst Harvard, Boston, MA USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
Blood Syst Res Inst, Viral Reference Lab, San Francisco, CA 94118 USA.
Blood Syst Res Inst, Repository Core, San Francisco, CA 94118 USA.
Univ Southampton, Southampton, Hants, England.
Southampton Gen Hosp, Southampton SO9 4XY, Hants, England.
Univ Toulouse 3, F-31062 Toulouse, France.
Plymouth Hosp NHS Trust, SW Liver Unit, Plymouth, Devon, England.
Rho, Chapel Hill, NC USA.
State Univ New York Downstate Coll Med, Brooklyn, NY USA.
Cambridge Univ Hosp NHS Fdn Trust, Cambridge, England.
Addenbrookes Hosp, Cambridge, England.
Univ Colorado, Denver, CO 80045 USA.
Menia Univ, Al Minya, Egypt.
Natl Hepatol & Trop Dis Res Inst, Viral Hepatitis Res Lab, Cairo, Egypt.
Frederick Natl Lab Canc Res, Canc & Inflammat Program, Expt Immunol Lab, Sci Applicat Int Corp Frederick, Frederick, MD USA.
RP Thomas, DL (reprint author), Johns Hopkins Sch Med, 1830 E Monument St,Suite 437, Baltimore, MD 21287 USA.
EM pduggal@jhsph.edu; dthomas@jhmi.edu
OI Edlin, Brian/0000-0001-8172-8797; Khakoo, Salim/0000-0002-4057-9091
FU Office of AIDS Research, National Institutes of Health; Frederick
National Laboratory for Cancer Research; Office of AIDS Research through
the Center for Inherited Diseases at Johns Hopkins University; National
Institute on Drug Abuse [R01013324, DA033541, DA12568, DA04334];
National Institute of Allergy and Infectious Diseases [U19AI088791,
AI082630]; Frederick National Laboratory for Cancer Research
[HHSN261200800001E]; National Institutes of Health; National Institute
of Allergy and Infectious Diseases; National Cancer Institute
[UO1-AI-35042, UL1-RR025005, UO1-AI-35043, UO1-AI-35039, UO1-AI-35040,
UO1-AI-35041]; National Institute of Allery and Infectious Diseases
[UO1-AI35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI34993,
UO1-AI-42590]; National Institute of Child Health and Human Development
[UO1-HD-32632]; [R01HL076902]; [R01-DA16159]; [R01-DA21550];
[UL1-RR024996]
FX Office of AIDS Research, National Institutes of Health, and Frederick
National Laboratory for Cancer Research.; This project was funded in
whole or in part by the Office of AIDS Research through the Center for
Inherited Diseases at Johns Hopkins University, the National Institute
on Drug Abuse (R01013324, DA033541, DA12568, and DA04334), the National
Institute of Allergy and Infectious Diseases (U19AI088791 and AI082630),
and the Frederick National Laboratory for Cancer Research (contract
HHSN261200800001E). This research was supported in part by the
Intramural Research Programs of the National Institutes of Health and
the Frederick National Laboratory for Cancer Research. The MACS is
funded by the National Institute of Allergy and Infectious Diseases,
with additional supplemental funding from the National Cancer Institute
(UO1-AI-35042, UL1-RR025005, UO1-AI-35043, UO1-AI-35039, UO1-AI-35040,
and UO1-AI-35041). The WIHS is funded by the National Institute of
Allery and Infectious Diseases (UO1-AI35004, UO1-AI-31834, UO1-AI-34994,
UO1-AI-34989, UO1-AI34993, and UO1-AI-42590) and by the National
Institute of Child Health and Human Development (UO1-HD-32632). The
REVELL cohort was funded by R01HL076902. Swann cohort was funded by
R01-DA16159, R01-DA21550, and UL1-RR024996.
NR 38
TC 82
Z9 82
U1 0
U2 8
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD FEB 19
PY 2013
VL 158
IS 4
BP 235
EP 245
DI 10.7326/0003-4819-158-4-201302190-00003
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 098WR
UT WOS:000315580300014
PM 23420232
ER
PT J
AU Johnson, AD
Hwang, SJ
Voorman, A
Morrison, A
Peloso, GM
Hsu, YH
Thanassoulis, G
Newton-Cheh, C
Rogers, IS
Hoffmann, U
Freedman, JE
Fox, CS
Psaty, BM
Boerwinkle, E
Cupples, LA
O'Donnell, CJ
AF Johnson, Andrew D.
Hwang, Shih-Jen
Voorman, Arend
Morrison, Alanna
Peloso, Gina M.
Hsu, Yi-Hsiang
Thanassoulis, George
Newton-Cheh, Christopher
Rogers, Ian S.
Hoffmann, Udo
Freedman, Jane E.
Fox, Caroline S.
Psaty, Bruce M.
Boerwinkle, Eric
Cupples, L. Adrienne
O'Donnell, Christopher J.
TI Resequencing and Clinical Associations of the 9p21.3 Region A
Comprehensive Investigation in the Framingham Heart Study
SO CIRCULATION
LA English
DT Article
DE atherosclerosis; calcium; genetics; myocardial infarction; risk factors
ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; SINGLE NUCLEOTIDE
POLYMORPHISMS; ABDOMINAL AORTIC-ANEURYSM; CHROMOSOME 9P21;
MYOCARDIAL-INFARCTION; COMMON SNPS; VARIANTS; LOCUS; ANRIL
AB Background-9p21.3 is among the most strongly replicated regions for cardiovascular disease. There are few reports of sequencing the associated 9p21.3 interval. We set out to sequence the 9p21.3 region followed by a comprehensive study of genetic associations with clinical and subclinical cardiovascular disease and its risk factors, as well as with copy number variation and gene expression, in the Framingham Heart Study (FHS).
Methods and Results-We sequenced 281 individuals (94 with myocardial infarction, 94 with high coronary artery calcium levels, and 93 control subjects free of elevated coronary artery calcium or myocardial infarction), followed by genotyping and association in >7000 additional FHS individuals. We assessed genetic associations with clinical and subclinical cardiovascular disease, risk factor phenotypes, and gene expression levels of the protein-coding genes CDKN2A and CDKN2B and the noncoding gene ANRIL in freshly harvested leukocytes and platelets. Within this large sample, we found strong associations of 9p21.3 variants with increased risk for myocardial infarction, higher coronary artery calcium levels, and larger abdominal aorta diameters and no evidence for association with traditional cardiovascular disease risk factors. No common protein-coding variation, variants in splice donor or acceptor sites, or copy number variation events were observed. By contrast, strong associations were observed between genetic variants and gene expression, particularly for a short isoform of ANRIL and for CDKN2B.
Conclusions-Our thorough genomic characterization of 9p21.3 suggests common variants likely account for observed disease associations and provides further support for the hypothesis that complex regulatory variation affecting ANRIL and CDKN2B gene expression may contribute to increased risk for clinically apparent and subclinical coronary artery disease and aortic disease. (Circulation. 2013;127:799-810.)
C1 [Johnson, Andrew D.; Hwang, Shih-Jen; Peloso, Gina M.; Thanassoulis, George; Fox, Caroline S.; Cupples, L. Adrienne; O'Donnell, Christopher J.] NHLBI, NIH, Framingham Heart Study, Framingham, MA USA.
[Johnson, Andrew D.; Hwang, Shih-Jen; Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[Voorman, Arend] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Morrison, Alanna; Boerwinkle, Eric] Baylor Coll Med, Texas Med Ctr, Program Human Genet, Houston, TX 77030 USA.
[Peloso, Gina M.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Hsu, Yi-Hsiang] Harvard Univ, Sch Med, Hebrew SeniorLife Inst Aging Res, Boston, MA USA.
[Thanassoulis, George] McGill Univ, Ctr Hlth, Montreal, PQ, Canada.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Rogers, Ian S.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Boston, MA USA.
[Rogers, Ian S.] Stanford Univ, Div Cardiovasc Med, Stanford, CA 94305 USA.
[Freedman, Jane E.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Hlth Res Inst, Seattle, WA USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
RP O'Donnell, CJ (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM odonnellc@nhlbi.nih.gov
RI Johnson, Andrew/G-6520-2013;
OI Cupples, L. Adrienne/0000-0003-0273-7965
FU National Heart, Lung, and Blood Institute (NHLBI) DNA Resequencing and
Genotyping Program [N01-HV-48194]; NHLBI's FHS [N01-HC-25195];
Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the
Department of Medicine at Boston University School of Medicine; Boston
Medical Center; National Institute of Arthritis and Musculoskeletal and
Skin Diseases [R21-AR056405]; NHLBI [RC2-HL02419, N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022, R01-HL-087641, R01-HL-59367, R01-HL-086694, N01-HC-85239,
N01-HC-85079, N01-HC-85080]; National Human Genome Research Institute
[U01-HG-004402]; National Institutes of Health [HHSN268200625226C,
UL1-RR-025005]; NIH Roadmap for Medical Research; National Institute on
Aging [AG-023629, AG-15928, AG-20098, AG-027058]; National Center of
Advancing Translational Technologies Clinical & Translational Science
Institute [UL1TR000124]; National Institute of Diabetes and Digestive
and Kidney Diseases [DK063491]; NHLBI. [N01-HC-85081, N01-HC-85082,
N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129,
N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
HHSN268201200036C, HL080295, HL087652, HL105756, 1T32 HL076136]
FX Resequencing provided via the National Heart, Lung, and Blood Institute
(NHLBI) DNA Resequencing and Genotyping Program by N01-HV-48194. Work on
CNV calling and the FHS LD map was supported by the NHLBI's FHS
(contract No. N01-HC-25195) and its contract with Affymetrix, Inc for
genotyping services (contract No. N02-HL-6-4278). A portion of this
research used the Linux Cluster for Genetic Analysis (LinGA-II), funded
by the Robert Dawson Evans Endowment of the Department of Medicine at
Boston University School of Medicine and Boston Medical Center. CNV
calling was supported by National Institute of Arthritis and
Musculoskeletal and Skin Diseases grant R21-AR056405. Whole genome
sequencing in CHS and ARIC was conducted as part of the CHARGE-S
(Cohorts for Heart and Aging Research in Genome Epidemiology Consortium)
sequencing programming supported by NHLBI Grand Opportunity grant
RC2-HL02419. The ARIC Study is supported by NHLBI contracts
N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020,
N01-HC-55021, and N01-HC-55022 and grants R01-HL-087641, R01-HL-59367,
and R01-HL-086694; National Human Genome Research Institute contract
U01-HG-004402; and National Institutes of Health contract
HHSN268200625226C. The infrastructure was supported in part by grant No.
UL1-RR-025005, a component of the National Institutes of Health and NIH
Roadmap for Medical Research. The CHS research was supported by NHLBI
contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129,
N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, and
HHSN268201200036C and NHLBI grants HL080295, HL087652, and HL105756,
with additional contribution from the National Institute of Neurological
Disorders and Stroke. Additional support was provided through AG-023629,
AG-15928, AG-20098, and AG-027058 from the National Institute on Aging.
See also the CHS Web site (http://www.chsnhlbi.org/pi.htm). DNA handling
and genotyping was supported in part by National Center of Advancing
Translational Technologies Clinical & Translational Science Institute
grant UL1TR000124 and National Institute of Diabetes and Digestive and
Kidney Diseases grant DK063491 to the Southern California Diabetes
Endocrinology Research Center. We thank Daniel Levy and Dr O'Donnell for
genotyping funding. Dr Rogers was supported by NHLBI 1T32 HL076136. Dr
Johnson was supported by an NHLBI Intramural Research Training Award
fellowship.
NR 41
TC 31
Z9 33
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 19
PY 2013
VL 127
IS 7
BP 799
EP 810
DI 10.1161/CIRCULATIONAHA.112.111559
PG 12
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 094YS
UT WOS:000315302200017
PM 23315372
ER
PT J
AU Magnuson, EA
Farkouh, ME
Fuster, V
Wang, KJ
Vilain, K
Li, HY
Appelwick, J
Muratov, V
Sleeper, LA
Boineau, R
Abdallah, M
Cohen, DJ
AF Magnuson, Elizabeth A.
Farkouh, Michael E.
Fuster, Valentin
Wang, Kaijun
Vilain, Katherine
Li, Haiyan
Appelwick, Jaime
Muratov, Victoria
Sleeper, Lynn A.
Boineau, Robin
Abdallah, Mouin
Cohen, David J.
CA FREEDOM Trial Investigators
TI Cost-Effectiveness of Percutaneous Coronary Intervention With Drug
Eluting Stents Versus Bypass Surgery for Patients With Diabetes Mellitus
and Multivessel Coronary Artery Disease Results From the FREEDOM Trial
SO CIRCULATION
LA English
DT Article
DE coronary artery bypass grafting; cost-benefit analysis; diabetes
mellitus; drug-eluting stents; percutaneous coronary intervention
ID QUALITY-OF-LIFE; MEDICAL COSTS; REVASCULARIZATION; ANGIOPLASTY;
METAANALYSIS; ARTS; RANDOMIZATION; STANDARD; EFFICACY; OUTCOMES
AB Background-Studies from the balloon angioplasty and bare metal stent eras have demonstrated that coronary artery bypass grafting (CABG) is cost-effective compared with percutaneous coronary intervention (PCI) for patients undergoing multivessel coronary revascularization-particularly among patients with complex coronary artery disease or diabetes mellitus. Whether these results apply in the drug-eluting stent (DES) era is unknown.
Methods and Results-Between 2005 and 2010, 1900 patients with diabetes mellitus and multivessel coronary artery disease were randomized to PCI with DES (DES-PCI; n=953) or CABG (n=947). Costs were assessed from the perspective of the U. S. health care system. Health state utilities were assessed using the EuroQOL 5 dimension 3 level questionnaire. A patient-level microsimulation model based on U. S. life-tables and in-trial results was used to estimate lifetime cost-effectiveness. Although initial procedural costs were lower for CABG, total costs for the index hospitalization were $8622 higher per patient. Over the next 5 years, follow-up costs were higher with PCI, owing to more frequent repeat revascularization and higher outpatient medication costs. Nonetheless, cumulative 5-year costs remained $3641 higher per patient with CABG. Although there were only modest gains in survival with CABG during the trial period, when the in-trial results were extended to a lifetime horizon, CABG was projected to be economically attractive relative to DES-PCI, with substantial gains in both life expectancy and quality-adjusted life expectancy and incremental cost-effectiveness ratios <$10 000 per life-year or quality-adjusted life-year gained across a broad range of assumptions regarding the effect of CABG on post-trial survival and costs.
Conclusions-Despite higher initial costs, CABG is a highly cost-effective revascularization strategy compared with DES-PCI for patients with diabetes mellitus and multivessel coronary artery disease.
C1 [Magnuson, Elizabeth A.; Wang, Kaijun; Vilain, Katherine; Li, Haiyan; Appelwick, Jaime; Abdallah, Mouin; Cohen, David J.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA.
[Farkouh, Michael E.; Fuster, Valentin] Mt Sinai Sch Med, Dept Cardiol, New York, NY USA.
[Farkouh, Michael E.] Univ Toronto, Peter Munk Cardiac Ctr, Toronto, ON, Canada.
[Farkouh, Michael E.] Univ Toronto, Li Ka Shing Knowledge Inst, Toronto, ON, Canada.
[Muratov, Victoria; Sleeper, Lynn A.] New England Res Inst, Watertown, MA 02172 USA.
[Boineau, Robin] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Cohen, DJ (reprint author), Univ Missouri, Kansas City Sch Med, St Lukes Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA.
EM dcohen@saint-lukes.org
RI Caramori, Paulo/I-1370-2012; Fuster, Valentin/H-4319-2015
OI Fuster, Valentin/0000-0002-9043-9986
FU National Heart, Lung, and Blood Institute (NHLBI) [01HL071988,
01HL092989]; Eli Lilly; Abbott Vascular; Astra Zeneca; Boston
Scientific; Daiichi Sankyo; Edwards Lifesciences; Medtronic;
Bristol-Myers Squibb; Cordis; Sanofi-Aventis; Biomet; Jannsen
Pharmaceuticals
FX The FREEDOM Trial was supported by U01 grants #01HL071988 and
#01HL092989 from the National Heart, Lung, and Blood Institute (NHLBI)
with provision of stents from Cordis, Johnson and Johnson, and Boston
Scientific, provision of abciximab and an unrestricted research grant
from Eli Lilly, and provision of clopidogrel from Sanofi-Aventis and
Bristol Myers Squibb. The views expressed are not necessarily the views
of NHLBI, but of the individual authors.; Dr Magnuson has received grant
support from Abbott Vascular, Astra Zeneca, Boston Scientific, Daiichi
Sankyo, Edwards Lifesciences, Eli Lilly, and Medtronic. Dr Farkouh has
received grant support from Eli Lilly and other research support from
Boston Scientific, Bristol-Myers Squibb, Cordis, Eli Lilly, and
Sanofi-Aventis. Dr Cohen has received grant support from Abbott
Vascular, Astra Zeneca, Biomet, Boston Scientific, Edwards Lifesciences,
Eli Lilly, Jannsen Pharmaceuticals, and Medtronic and consulting fees
from Abbott Vascular, Astra Zeneca, Eli Lilly and Medtronic. The other
authors report no conflicts.
NR 36
TC 39
Z9 40
U1 2
U2 15
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 19
PY 2013
VL 127
IS 7
BP 820
EP 831
DI 10.1161/CIRCULATIONAHA.112.147488
PG 12
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 094YS
UT WOS:000315302200019
PM 23277307
ER
PT J
AU Bagci, U
Yao, JH
Miller-Jaster, K
Chen, XJ
Mollura, DJ
AF Bagci, Ulas
Yao, Jianhua
Miller-Jaster, Kirsten
Chen, Xinjian
Mollura, Daniel J.
TI Predicting Future Morphological Changes of Lesions from Radiotracer
Uptake in 18F-FDG-PET Images
SO PLOS ONE
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; F-18-FDG PET; SEGMENTATION; TEXTURE;
HETEROGENEITY; VARIANCE; VOLUMES
AB We introduce a novel computational framework to enable automated identification of texture and shape features of lesions on F-18-FDG-PET images through a graph-based image segmentation method. The proposed framework predicts future morphological changes of lesions with high accuracy. The presented methodology has several benefits over conventional qualitative and semi-quantitative methods, due to its fully quantitative nature and high accuracy in each step of (i) detection, (ii) segmentation, and (iii) feature extraction. To evaluate our proposed computational framework, thirty patients received 2 F-18-FDG-PET scans (60 scans total), at two different time points. Metastatic papillary renal cell carcinoma, cerebellar hemongioblastoma, non-small cell lung cancer, neurofibroma, lymphomatoid granulomatosis, lung neoplasm, neuroendocrine tumor, soft tissue thoracic mass, nonnecrotizing granulomatous inflammation, renal cell carcinoma with papillary and cystic features, diffuse large B-cell lymphoma, metastatic alveolar soft part sarcoma, and small cell lung cancer were included in this analysis. The radiotracer accumulation in patients' scans was automatically detected and segmented by the proposed segmentation algorithm. Delineated regions were used to extract shape and textural features, with the proposed adaptive feature extraction framework, as well as standardized uptake values (SUV) of uptake regions, to conduct a broad quantitative analysis. Evaluation of segmentation results indicates that our proposed segmentation algorithm has a mean dice similarity coefficient of 85.75 +/- 1.75%. We found that 28 of 68 extracted imaging features were correlated well with SUVmax (p<0.05), and some of the textural features (such as entropy and maximum probability) were superior in predicting morphological changes of radiotracer uptake regions longitudinally, compared to single intensity feature such as SUVmax. We also found that integrating textural features with SUV measurements significantly improves the prediction accuracy of morphological changes (Spearman correlation coefficient = 0.8715, p= 1.0) underwent colposcopy and biopsy, as did a sample of double-negative women with an abnormal cervix at visual inspection or with risk factors for cervical lesions. Crude and verification bias-corrected sensitivities and specificities were estimated. In total, 8,265 women (98.8% of eligible) had complete screening results. Of these, 10.7% were HPV positive, 1.7% were Pap positive and 1.1% were positive by both tests. In all, 931 (11.3%) women were screen-positive, of whom 94.3% attended colposcopy. Additionally, 295 control women were invited for colposcopy, of whom 78% attended. In all, 42 CIN2, 45 CIN3 and 9 cancers were identified. Verification bias-corrected sensitivity for CIN2+ (95% confidence interval) was 92.7% (84.4-96.8) for HPV and 22.1% (16.4-29.2) for Pap; corresponding specificities were 92.0% (91.4-92.6) and 98.9% (98.7-99.0). In conclusion, in routine clinical practice in a developing country, HPV testing was four times more sensitive for CIN2+ than Pap testing, identifying three times more CIN2+ lesions; HPV testing was easily implemented in our established cervical cancer prevention program.
C1 [Ferreccio, Catterina] Pontificia Univ Catolica Chile, Sch Med, Dept Publ Hlth, Santiago 8330073, Chile.
[Isabel Barriga, Maria; Nunez, Felipe; Cartagena, Jaime; Branes, Jorge] Pontificia Univ Catolica Chile, Dept Ginecol & Obstet, Santiago 8330073, Chile.
[Lagos, Marcela; Poggi, Helena] Pontificia Univ Catolica Chile, Dept Lab Clin, Santiago 8330073, Chile.
[Katki, Hormuzd A.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Vinales, Daysi] Serv Salud Metropolitano S Oriente, Santiago, Chile.
RP Ferreccio, C (reprint author), Pontificia Univ Catolica Chile, Sch Med, Dept Publ Hlth, Marcoleta 434, Santiago 8330073, Chile.
EM cferrec@med.puc.cl
RI Katki, Hormuzd/B-4003-2015
FU Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT), a
Chilean State fund for research [1090597]
FX Grant sponsor: Fondo Nacional de Desarrollo Cientifico y Tecnologico
(FONDECYT), a Chilean State fund for research; Grant number: 1090597
NR 38
TC 15
Z9 18
U1 0
U2 16
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 FEB 15
PY 2013
VL 132
IS 4
BP 916
EP 923
DI 10.1002/ijc.27662
PG 8
WC Oncology
SC Oncology
GA 078AB
UT WOS:000314069400019
PM 22684726
ER
PT J
AU Mattoo, AR
Fitzgerald, DJ
AF Mattoo, Abid R.
Fitzgerald, David J.
TI Combination treatments with ABT-263 and an immunotoxin produce
synergistic killing of ABT-263-resistant small cell lung cancer cell
lines
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE SCLC; ABT-263; ABT-737; immunotoxin and Mcl-1
ID BCL-2 FAMILY INHIBITOR; PSEUDOMONAS EXOTOXIN; RECOMBINANT IMMUNOTOXINS;
PHASE-I; APOPTOSIS; IMMUNOTHERAPY; LEUKEMIA; ABT-737; PROTEINS; TOXINS
AB Synergistic killing was achieved when Small Cell Lung Cancer (SCLC) cell lines were incubated with ABT-263 and an immunotoxin directed to the transferrin receptor. SCLC lines are variably sensitive to the BH-3 only peptide mimetic, ABT-263. To determine their sensitivity to toxin-based reagents, we incubated four representative SCLC lines with a model Pseudomonas exotoxin-based immunotoxin directed to the transferrin receptor. Remarkably in 4-of-4 lines, there was little evidence of immunotoxin-mediated cytotoxicity despite near complete inhibition of protein synthesis. However, when combinations of ABT-263 and immunotoxin were added to the ABT-263-resistant cell lines (H196 and H69AR), there was synergistic killing as evidenced by increased activation of caspase 3/7, annexin V staining, and loss of cell integrity. Synergistic killing was evident at 6 hr and correlated with loss of Mcl-1. This synergy was also noted when the closely related compound ABT-737 was combined with the same immunotoxin. To establish that the synergy seen in tissue culture could be achieved in vivo, H69AR cells were grown as tumors in nude mice and shown to be susceptible to the killing action of an immunotoxin-ABT-737 combination but not to either agent alone. When immunotoxin-ABT combinations were added to ABT-263-sensitive lines (H146 and H1417), killing was additive. Our data support combination approaches for treating ABT-263-resistant SCLC with ABT-263 and a second agent that provides synergistic killing action.
C1 [Mattoo, Abid R.; Fitzgerald, David J.] NCI, Biotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH,HHS, Bethesda, MD 20819 USA.
RP Fitzgerald, DJ (reprint author), NCI, Biotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH,HHS, Bldg 37,Room 5124, Bethesda, MD 20819 USA.
EM djpf@helix.nih.gov
OI MATTOO, ABID/0000-0002-4947-0113
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX Grant sponsors: Intramural Research Program of the National Institutes
of Health, National Cancer Institute, Center for Cancer Research
NR 31
TC 16
Z9 16
U1 1
U2 12
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 FEB 15
PY 2013
VL 132
IS 4
BP 978
EP 987
DI 10.1002/ijc.27732
PG 10
WC Oncology
SC Oncology
GA 078AB
UT WOS:000314069400026
PM 22821746
ER
PT J
AU Brinas, RP
Maetani, M
Barchi, JJ
AF Brinas, Raymond P.
Maetani, Micah
Barchi, Joseph J., Jr.
TI A survey of place-exchange reaction for the preparation of water-soluble
gold nanoparticles
SO JOURNAL OF COLLOID AND INTERFACE SCIENCE
LA English
DT Article
DE Gold nanoparticles; Place-exchange reaction; Water-soluble ligands;
Peptides; Carbohydrates; Amino acids; Ligands; Glycopeptides; Water
soluble
ID THOMSEN-FRIEDENREICH DISACCHARIDE; CLUSTER MOLECULES; AU NANOPARTICLES;
CONTRAST AGENT; LIGANDS; CHARGE; IDENTIFICATION; NANOCRYSTALS; DYNAMICS;
ANTIGEN
AB Water-soluble gold nanoparticles (AuNPs) have gained considerable attention because they offer a myriad of potential applications, especially in the fields of biology and medicine. One method to prepare such gold nanoparticles is through the well-known Murray place-exchange reaction. In this method, precursor gold nanoparticles, bearing labile ligands and with very good size distribution, are synthesized first, and then reacted with a large excess of the desired ligand. We report a comparison of the reactivity of several known precursor gold nanoparticles (citrate-stabilized, pentanethiol-stabilized, tetraoctylammonium bromide-stabilized, and 4-dimethylaminopyridine-stabilized) to several biologically relevant ligands, including amino acids, peptides, and carbohydrates. We found that citrate-stabilized and 4-dimethylaminopyridine-stabilized gold nanoparticles have broader reactivities than the other precursors studied. Citrate-stabilized gold nanoparticles are more versatile precursors because they can be prepared in a wide range of sizes and are very stable. The hydrophobic pentane-stabilized gold nanoparticles made them "inert" toward highly water-soluble ligands. Tetraoctylammonium bromide-stabilized gold nanoparticles exhibited selective reactivity, especially for small, unhindered and amphiphilic ligands. Depending on the desired ligand and size of AuNPs, a judicious selection of the available precursors can be made for use in place-exchange reactions. In preparing water-soluble AuNPs with biologically relevant ligands, the nature of the incoming ligand and the size of the AuNP should be taken into account in order to choose the most suitable place-exchange procedure. Published by Elsevier Inc.
C1 [Brinas, Raymond P.; Maetani, Micah; Barchi, Joseph J., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res, Ft Detrick, MD 21702 USA.
RP Barchi, JJ (reprint author), NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res, 376 Boyles St,POB B, Ft Detrick, MD 21702 USA.
EM Barchi@helix.nih.gov
RI Barchi Jr., Joseph/N-3784-2014
FU Intramural program of the National Cancer Institute at the National
Institutes of Health
FX We are grateful to Dr. Kunio Nagashima for performing the TEM analyses.
We also appreciate the assistance of Dr. Sergei Tarasov and Ms. Marzena
Dyba with the UV-vis spectrophotometer and Souvik Biswas for help with
the high pH exchange reactions. This work was supported by funds from
the Intramural program of the National Cancer Institute at the National
Institutes of Health. We gratefully thank the Biophysics Resource of the
Structural Biophysics Laboratory, CCR, NCI for help with nanoparticle
characterization.
NR 51
TC 13
Z9 13
U1 0
U2 76
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0021-9797
J9 J COLLOID INTERF SCI
JI J. Colloid Interface Sci.
PD FEB 15
PY 2013
VL 392
BP 415
EP 421
DI 10.1016/j.jcis.2012.06.042
PG 7
WC Chemistry, Physical
SC Chemistry
GA 078YK
UT WOS:000314136800055
PM 23149107
ER
PT J
AU Watts, DH
Williams, PL
Kacanek, D
Griner, R
Rich, K
Hazra, R
Mofenson, LM
Mendez, HA
AF Watts, D. Heather
Williams, Paige L.
Kacanek, Deborah
Griner, Raymond
Rich, Kenneth
Hazra, Rohan
Mofenson, Lynne M.
Mendez, Hermann A.
CA Pediat HIV-AIDS Cohort Study
TI Combination Antiretroviral Use and Preterm Birth
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE preterm birth; antiretrovirals; pregnancy; small for gestational age
ID HIV-INFECTED WOMEN; PREGNANT-WOMEN; PREMATURE DELIVERY; INCREASED RISK;
IN-UTERO; PROTEASE INHIBITORS; UNITED-KINGDOM; THERAPY; EXPOSURE;
OUTCOMES
AB Background. Use of antiretroviral drugs (ARVs) during pregnancy has been associated with higher risk of preterm birth.
Methods. The Pediatric HIV/AIDS Cohort Study network's Surveillance Monitoring for ART Toxicities study is a US-based cohort of human immunodeficiency virus (HIV)-exposed uninfected children. We evaluated maternal ARV use during pregnancy and the risk of any type of preterm birth (ie, birth before 37 completed weeks of gestation), the risk of spontaneous preterm birth (ie, preterm birth that occurred after preterm labor or membrane rupture, without other complications), and the risk of small for gestational age (SGA; ie, a birth weight of <10th percentile for gestational age). Multivariable logistic regression models were used to evaluate the association of ARVs and timing of exposure, while adjusting for maternal characteristics.
Results. Among 1869 singleton births, 18.6% were preterm, 10.2% were spontaneous preterm, and 7.3% were SGA. A total of 89% used 3-drug combination ARV regimens during pregnancy. In adjusted models, the odds of preterm birth and spontaneous preterm birth were significantly greater among mothers who used protease inhibitors during the first trimester (adjusted odds ratios, 1.55 and 1.59, respectively) but not among mothers who used nonnucleoside reverse-transcriptase inhibitor or triple-nucleoside regimens during the first trimester. Combination ARV exposure starting later in pregnancy was not associated with increased risk. No associations were observed between SGA and exposure to combination ARV regimens.
Conclusions. Protease inhibitor use early in pregnancy may be associated with increased risk for prematurity.
C1 [Watts, D. Heather; Hazra, Rohan; Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA.
[Williams, Paige L.; Kacanek, Deborah; Griner, Raymond] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Rich, Kenneth] Univ Illinois, Chicago, IL USA.
[Mendez, Hermann A.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
RP Watts, DH (reprint author), 6100 Execut Blvd,Rm 4B11, Bethesda, MD USA.
EM hw59i@nih.gov
OI Mofenson, Lynne/0000-0002-2818-9808
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Allergy and Infectious Diseases;
National Institute on Drug Abuse; National Institute of Mental Health;
National Institute of Deafness and Other Communication Disorders;
National Heart Lung and Blood Institute; National Institute of
Neurological Disorders and Stroke; National Institute on Alcohol Abuse
and Alcoholism through the Harvard University School of Public Health
[U01 HD052102-04]; National Institute on Alcohol Abuse and Alcoholism
through the Tulane University School of Medicine [U01 HD052104-01]
FX This work was supported by the Eunice Kennedy Shriver National Institute
of Child Health and Human Development, with cofunding from the National
Institute of Allergy and Infectious Diseases, the National Institute on
Drug Abuse, the National Institute of Mental Health, the National
Institute of Deafness and Other Communication Disorders, the National
Heart Lung and Blood Institute, the National Institute of Neurological
Disorders and Stroke, and the National Institute on Alcohol Abuse and
Alcoholism, through cooperative agreements with the Harvard University
School of Public Health (U01 HD052102-04) and the Tulane University
School of Medicine (U01 HD052104-01).
NR 30
TC 39
Z9 39
U1 0
U2 13
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 FEB 15
PY 2013
VL 207
IS 4
BP 612
EP 621
DI 10.1093/infdis/jis728
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 078TG
UT WOS:000314121800010
PM 23204173
ER
PT J
AU Hurley, A
Smith, M
Karpova, T
Hasley, RB
Belkina, N
Shaw, S
Balenga, N
Druey, KM
Nickel, E
Packard, B
Imamichi, H
Hu, ZH
Follmann, D
McNally, J
Higgins, J
Sneller, M
Lane, HC
Catalfamo, M
AF Hurley, Amanda
Smith, Mindy
Karpova, Tatiana
Hasley, Rebecca B.
Belkina, Natalya
Shaw, Stephen
Balenga, Nariman
Druey, Kirk M.
Nickel, Erin
Packard, Beverly
Imamichi, Hiromi
Hu, Zonghui
Follmann, Dean
McNally, James
Higgins, Jeanette
Sneller, Michael
Lane, H. Clifford
Catalfamo, Marta
TI Enhanced Effector Function of CD8(+) T Cells From Healthy Controls and
HIV-Infected Patients Occurs Through Thrombin Activation of
Protease-Activated Receptor 1
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE PAR-1; T cells; thrombin; HIV pathogenesis; coagulation; inflammation
ID ANTIGEN-PRESENTING CELLS; CARDIOVASCULAR-DISEASE; ANTIRETROVIRAL
THERAPY; DANGER MODEL; COAGULATION; INFLAMMATION; SEPSIS; POLARIZATION;
EXPRESSION; ERM
AB Disruption of vascular integrity by trauma and other tissue insults leads to inflammation and activation of the coagulation cascade. The serine protease thrombin links these 2 processes. The proinflammatory function of thrombin is mediated by activation of protease-activated receptor 1 (PAR-1). We found that peripheral blood effector memory CD4(+) and CD8(+) T lymphocytes expressed PAR-1 and that expression was increased in CD8(+) T cells from human immunodeficiency virus (HIV)-infected patients. Thrombin enhanced cytokine secretion in CD8(+) T cells from healthy controls and HIV-infected patients. In addition, thrombin induced chemokinesis, but not chemotaxis, of CD8(+) T cells, which led to structural changes, including cell polarization and formation of a structure rich in F-actin and phosphorylated ezrin-radexin-moesin proteins. These findings suggest that thrombin mediates cross-talk between the coagulation system and the adaptive immune system at sites of vascular injury through increased T-cell motility and production of proinflammatory cytokines.
C1 [Hurley, Amanda; Smith, Mindy; Hasley, Rebecca B.; Nickel, Erin; Imamichi, Hiromi; Sneller, Michael; Lane, H. Clifford; Catalfamo, Marta] NIAID, Immunoregulat Lab, NIH, CMRS, Bethesda, MD 20892 USA.
[Balenga, Nariman; Druey, Kirk M.] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA.
[Hu, Zonghui; Follmann, Dean] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
[Karpova, Tatiana; McNally, James] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Belkina, Natalya; Shaw, Stephen] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Packard, Beverly] OncoImmunin, Gaithersburg, MD USA.
[Higgins, Jeanette] SAIC, AIDS Monitoring Labs, Frederick, MD USA.
RP Catalfamo, M (reprint author), NIAID, Immunoregulat Lab, NIH, CMRS, Bldg 10,Room 11B07,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM catalfam@mail.nih.gov
RI Aghaei Balenga, Nariman/A-5895-2011
OI Aghaei Balenga, Nariman/0000-0002-2741-9595
FU National Institute of Allergy and Infectious Diseases, National
Institute of Health (NIH); National Cancer Institute, NIH
[HHSN261200800001E]
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institute of Health (NIH; intramural research program) and the National
Cancer Institute, NIH (contract HHSN261200800001E).
NR 50
TC 9
Z9 9
U1 0
U2 5
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 FEB 15
PY 2013
VL 207
IS 4
BP 638
EP 650
DI 10.1093/infdis/jis730
PG 13
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 078TG
UT WOS:000314121800013
PM 23204166
ER
PT J
AU Gonzalez-Castillo, J
Duthie, KN
Saad, ZS
Chu, C
Bandettini, PA
Luh, WM
AF Gonzalez-Castillo, Javier
Duthie, Kristen N.
Saad, Ziad S.
Chu, Carlton
Bandettini, Peter A.
Luh, Wen-Ming
TI Effects of image contrast on functional MRI image registration
SO NEUROIMAGE
LA English
DT Article
ID MAGNETIC-RESONANCE; MOTION CORRECTION; ENHANCED MRI; BRAIN; GADOLINIUM;
FMRI; ROBUST; ACTIVATIONS; SOFTWARE; ACCURATE
AB Lack of tissue contrast and existing inhomogeneous bias fields from multi-channel coils have the potential to degrade the output of registration algorithms; and consequently degrade group analysis and any attempt to accurately localize brain function. Non-invasive ways to improve tissue contrast in fMRI images include the use of low flip angles (FAs) well below the Ernst angle and longer repetition times (TR). Techniques to correct intensity inhomogeneity are also available in most mainstream fMRI data analysis packages; but are not used as part of the pre-processing pipeline in many studies. In this work, we use a combination of real data and simulations to show that simple-to-implement acquisition/pre-processing techniques can significantly improve the outcome of both functional-to-functional and anatomical-to-functional image registrations. We also emphasize the need of tissue contrast on EPI images to be able to appropriately evaluate the quality of the alignment. In particular, we show that the use of low FAs (e.g., 0 40), when physiological noise considerations permit such an approach, significantly improves accuracy, consistency and stability of registration for data acquired at relatively short TRs (TR <= 2 s). Moreover, we also show that the application of bias correction techniques significantly improves alignment both for array-coil data (known to contain high intensity inhomogeneity) as well as birdcage-coil data. Finally, improvements in alignment derived from the use of the first infinite-TR volumes (ITVs) as targets for registration are also demonstrated. For the purpose of quantitatively evaluating the different scenarios, two novel metrics were developed: Mean Voxel Distance (MVD) to evaluate registration consistency, and Deviation of Mean Voxel Distance (dMVD) to evaluate registration stability across successive alignment attempts. Published by Elsevier Inc.
C1 [Gonzalez-Castillo, Javier; Duthie, Kristen N.; Chu, Carlton; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, NIH, Bethesda, MD 20892 USA.
[Bandettini, Peter A.; Luh, Wen-Ming] NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA.
RP Gonzalez-Castillo, J (reprint author), NIMH, Sect Funct Imaging Methods, NIH, Bethesda, MD 20892 USA.
EM javier.gonzalez-castillo@nih.gov
OI Gonzalez-Castillo, Javier/0000-0002-6520-5125
FU Intramural Research Program of the National Institute of Mental Health
FX The authors would also like to thank Dr. Gang Chen and Daniel Glen from
the Scientific and Statistical Computing Core at the National Institute
of Mental Health for their invaluable help during the preparation of
this manuscript. This research was supported by the Intramural Research
Program of the National Institute of Mental Health. This study utilized
the high-performance computational capabilities of the Biowulf Linux
cluster at the National Institutes of Health, Bethesda, Md.
(http://biowulf.nih.gov).
NR 38
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Z9 5
U1 0
U2 23
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 FEB 15
PY 2013
VL 67
BP 163
EP 174
DI 10.1016/j.neuroimage.2012.10.076
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 079BG
UT WOS:000314144600016
PM 23128074
ER
PT J
AU Kong, XF
Vogt, G
Itan, Y
Macura-Biegun, A
Szaflarska, A
Kowalczyk, D
Chapgier, A
Abhyankar, A
Furthner, D
Khayat, CD
Okada, S
Bryant, VL
Bogunovic, D
Kreins, A
Moncada-Velez, M
Migaud, M
Al-Ajaji, S
Al-Muhsen, S
Holland, SM
Abel, L
Picard, C
Chaussabel, D
Bustamante, J
Casanova, JL
Boisson-Dupuis, S
AF Kong, Xiao-Fei
Vogt, Guillaume
Itan, Yuval
Macura-Biegun, Anna
Szaflarska, Anna
Kowalczyk, Danuta
Chapgier, Ariane
Abhyankar, Avinash
Furthner, Dieter
Khayat, Claudia Djambas
Okada, Satoshi
Bryant, Vanessa L.
Bogunovic, Dusan
Kreins, Alexandra
Moncada-Velez, Marcela
Migaud, Melanie
Al-Ajaji, Sulaiman
Al-Muhsen, Saleh
Holland, Steven M.
Abel, Laurent
Picard, Capucine
Chaussabel, Damien
Bustamante, Jacinta
Casanova, Jean-Laurent
Boisson-Dupuis, Stephanie
TI Haploinsufficiency at the human IFNGR2 locus contributes to
mycobacterial disease
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID INTERFERON-GAMMA-RECEPTOR; SEQUENCING-BASED DISCOVERY; CALMETTE-GUERIN
INFECTION; GENETIC DISSECTION; CLINICAL-FEATURES; MEDIATED IMMUNITY;
STAT1 DEFICIENCY; HUMAN-MODEL; BETA CHAIN; CELL
AB Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare syndrome, the known genetic etiologies of which impair the production of, or the response to interferon-gamma (IFN-). We report here a patient (P1) with MSMD whose cells display mildly impaired responses to IFN-, at levels, however, similar to those from MSMD patients with autosomal recessive (AR) partial IFN-R2 or STAT1 deficiency. Whole-exome sequencing (WES) and Sanger sequencing revealed only one candidate variation for both MSMD-causing and IFN--related genes. P1 carried a heterozygous frame-shift IFNGR2 mutation inherited from her father. We show that the mutant allele is intrinsically loss-of-function and not dominant-negative, suggesting haploinsufficiency at the IFNGR2 locus. We also show that Epstein-Barr virus transformed B lymphocyte cells from 10 heterozygous relatives of patients with AR complete IFN-R2 deficiency respond poorly to IFN-, in some cases as poorly as the cells of P1. Naive CD4 T cells and memory IL-4-producing T cells from these individuals also responded poorly to IFN-, whereas monocytes and monocyte-derived macrophages (MDMs) did not. This is consistent with the lower levels of expression of IFN-R2 in lymphoid than in myeloid cells. Overall, MSMD in this patient is probably due to autosomal dominant (AD) IFN-R2 deficiency, resulting from haploinsufficiency, at least in lymphoid cells. The clinical penetrance of AD IFN-R2 deficiency is incomplete, possibly due, at least partly, to the variability of cellular responses to IFN- in these individuals.
C1 [Kong, Xiao-Fei; Vogt, Guillaume; Itan, Yuval; Abhyankar, Avinash; Okada, Satoshi; Bryant, Vanessa L.; Bogunovic, Dusan; Kreins, Alexandra; Moncada-Velez, Marcela; Casanova, Jean-Laurent; Boisson-Dupuis, Stephanie] Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA.
[Vogt, Guillaume; Chapgier, Ariane; Migaud, Melanie; Abel, Laurent; Picard, Capucine; Bustamante, Jacinta; Casanova, Jean-Laurent; Boisson-Dupuis, Stephanie] INSERM, Lab Human Genet Infect Dis, Necker Branch, U980, F-75015 Paris, France.
[Vogt, Guillaume; Chapgier, Ariane; Abel, Laurent; Picard, Capucine; Bustamante, Jacinta; Casanova, Jean-Laurent; Boisson-Dupuis, Stephanie] Univ Paris 05, Paris Cite Sorbonne, Necker Med Sch, F-75015 Paris, France.
[Macura-Biegun, Anna; Szaflarska, Anna; Kowalczyk, Danuta] Jagiellonian Univ, Coll Med, Dept Clin Immunol, PL-30663 Krakow, Poland.
[Furthner, Dieter] Women & Childrens Hosp Linz, Landes Frauen & Kinderklin Linz, A-4020 Linz, Austria.
[Khayat, Claudia Djambas] Hotel Dieu France Hosp, Dept Pediat, Beirut, Lebanon.
[Moncada-Velez, Marcela] Univ Antioquia, Sch Med, Grp Primary Immunodeficiencies, Medellin, Colombia.
[Al-Ajaji, Sulaiman] King Abdul Aziz Med City, Dept Pediat, Riyadh 11426, Saudi Arabia.
[Al-Muhsen, Saleh] King Saud Univ, Dept Pediat, Coll Med, Novel Primary Immunodeficiency & Infect Dis Progr, Riyadh 11451, Saudi Arabia.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Chaussabel, Damien] Benaroya Res Inst, Seattle, WA 98101 USA.
[Picard, Capucine; Casanova, Jean-Laurent] Hop Necker Enfants Malad, AP HP, Pediat Immunol Hematol Unit, F-75015 Paris, France.
[Picard, Capucine; Bustamante, Jacinta] Hop Necker Enfants Malad, AP HP, Ctr Primary Immunodeficiencies, F-75015 Paris, France.
RP Casanova, JL (reprint author), Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, 1230 York Ave,POB 163, New York, NY 10065 USA.
EM jean-laurent.casanova@rockefeller.edu
RI Vogt, Guillaume/L-6046-2015; Okada, Satoshi/B-8901-2011;
OI Vogt, Guillaume/0000-0001-8192-1247; Okada, Satoshi/0000-0002-4622-5657;
Picard, Capucine/0000-0001-8788-5056; Chaussabel,
Damien/0000-0002-6131-7242
FU Stony Wold-Herbert Fund; Choh-Hao Li Memorial Fund Scholar award;
Shanghai Educational Development Foundation; AXA Research Fund;
Fondation Medicale Medische Stichting Mathilde E. Horlait-Dapens; St
Giles Foundation; Jeffrey Modell Foundation; Rockefeller University
Center for Clinical and Translational Science from the National Center
for Research Resources [8UL1TR000043]; National Center for Advancing
Sciences (NCATS), National Institutes of Health; National Institute of
Allergy and Infectious Diseases [5R01AI089970-02]; Rockefeller
University; European Research Council (ERC); Talecris BioTherapeutics
FX X.F.K. was supported by the Stony Wold-Herbert Fund, Choh-Hao Li
Memorial Fund Scholar award and the Shanghai Educational Development
Foundation, Y.I. is supported by the AXA Research Fund, V. L. B. is
supported by the Stony Wold-Herbert Fund and A. K. is supported by the
Fondation Medicale Medische Stichting Mathilde E. Horlait-Dapens. The
Laboratory of Human Genetics of Infectious Diseases is supported in part
by grants from the St Giles Foundation, the Jeffrey Modell Foundation,
The Rockefeller University Center for Clinical and Translational Science
grant number 8UL1TR000043 from the National Center for Research
Resources and the National Center for Advancing Sciences (NCATS),
National Institutes of Health, the National Institute of Allergy and
Infectious Diseases grant number 5R01AI089970-02, The Rockefeller
University and the European Research Council (ERC). J.L.C. received a
research grant from the Jeffrey Modell Foundation in collaboration with
Talecris BioTherapeutics. The funder was not involved in the study
design; collection, analysis and interpretation of data; writing of the
paper or decision to submit for publication.
NR 52
TC 16
Z9 17
U1 0
U2 8
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 FEB 15
PY 2013
VL 22
IS 4
BP 769
EP 781
DI 10.1093/hmg/dds484
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 078RI
UT WOS:000314116600013
PM 23161749
ER
PT J
AU Henrion, M
Frampton, M
Scelo, G
Purdue, M
Ye, YQ
Broderick, P
Ritchie, A
Kaplan, R
Meade, A
McKay, J
Johansson, M
Lathrop, M
Larkin, J
Rothman, N
Wang, ZM
Chow, WH
Stevens, VL
Diver, WR
Gapstur, SM
Albanes, D
Virtamo, J
Wu, XF
Brennan, P
Chanock, S
Eisen, T
Houlston, RS
AF Henrion, Marc
Frampton, Matthew
Scelo, Ghislaine
Purdue, Mark
Ye, Yuanqing
Broderick, Peter
Ritchie, Alastair
Kaplan, Richard
Meade, Angela
McKay, James
Johansson, Mattias
Lathrop, Mark
Larkin, James
Rothman, Nathaniel
Wang, Zhaoming
Chow, Wong-Ho
Stevens, Victoria L.
Diver, W. Ryan
Gapstur, Susan M.
Albanes, Demetrius
Virtamo, Jarmo
Wu, Xifeng
Brennan, Paul
Chanock, Stephen
Eisen, Timothy
Houlston, Richard S.
TI Common variation at 2q22.3 (ZEB2) influences the risk of renal cancer
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CELL CARCINOMA; SUSCEPTIBILITY LOCI; KIDNEY
CANCER; DISEASE; COMPLEX; 2P21
AB Genome-wide association studies (GWASs) of renal cell cancer (RCC) have identified four susceptibility loci thus far. To identify an additional RCC common susceptibility locus, we conducted a GWAS and performed a meta-analysis with published GWASs (totalling 2215 cases and 8566 controls of European background) and followed up the most significant association signals [nine single nucleotide polymorphisms (SNPs) in eight genomic regions] in 3739 cases and 8786 controls. A combined analysis identified a novel susceptibility locus mapping to 2q22.3 marked by rs12105918 (P 1.80 10(8); odds ratio 1.29, 95 CI: 1.181.41). The signal localizes to intron 2 of the ZEB2 gene (zinc finger E box-binding homeobox 2). Our findings suggest that genetic variation in ZEB2 influences the risk of RCC. This finding provides further insights into the genetic and biological basis of inherited genetic susceptibility to RCC.
C1 [Henrion, Marc; Frampton, Matthew; Broderick, Peter; Houlston, Richard S.] Inst Canc Res, Sect Canc Genet, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England.
[Scelo, Ghislaine; McKay, James; Johansson, Mattias; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Purdue, Mark; Rothman, Nathaniel; Wang, Zhaoming; Chow, Wong-Ho; Albanes, Demetrius; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Ye, Yuanqing; Chow, Wong-Ho; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Div Canc Prevent & Populat Sci, Dept Epidemiol, Houston, TX 77030 USA.
[Ritchie, Alastair; Kaplan, Richard; Meade, Angela] MRC Clin Trials Unit, London WC2B 6NH, England.
[Lathrop, Mark] Commissariat Energie Atom, Inst Genom, Ctr Natl Genotypage, F-91000 Evry, France.
[Larkin, James] Royal Marsden NHS Fdn Trust, London, England.
[Wang, Zhaoming] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Stevens, Victoria L.; Diver, W. Ryan; Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, FIN-00300 Helsinki, Finland.
[Eisen, Timothy] Cambridge Univ Hlth Partners, Cambridge, England.
RP Houlston, RS (reprint author), Inst Canc Res, Sect Canc Genet, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England.
EM richard.houlston@icr.ac.uk
RI Albanes, Demetrius/B-9749-2015;
OI Henrion, Marc/0000-0003-1242-839X; Houlston,
Richard/0000-0002-5268-0242; Broderick, Peter/0000-0002-8348-5829
FU MRC; Cancer Research UK; Bayer; Cancer Research UK [C1298/A8362,
C490/A10124]; Bobby Moore Fund; Leukaemia Lymphoma Research; NHS;
Intramural Research Program of the National Cancer Institute, NIH
FX SORCE is coordinated by the Medical Research Council (MRC) and funded
principally by the MRC and Cancer Research UK with an educational grant
from Bayer. Additional funding was provided by Cancer Research UK
(C1298/A8362 supported by the Bobby Moore Fund). Marc Henrion was
supported by Leukaemia Lymphoma Research. NHS funding for the Royal
Marsden Biomedical Research Centre and Cambridge University Health
Partners is acknowledged. Funding for the SEARCH team was provided by
Cancer Research UK (C490/A10124). The US kidney GWAS was funded by the
Intramural Research Program of the National Cancer Institute, NIH.
NR 24
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U1 0
U2 9
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 FEB 15
PY 2013
VL 22
IS 4
BP 825
EP 831
DI 10.1093/hmg/dds489
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 078RI
UT WOS:000314116600018
PM 23184150
ER
PT J
AU Algotar, AM
Stratton, MS
Ahmann, FR
Ranger-Moore, J
Nagle, RB
Thompson, PA
Slate, E
Hsu, CH
Dalkin, BL
Sindhwani, P
Holmes, MA
Tuckey, JA
Graham, DL
Parnes, HL
Clark, LC
Stratton, SP
AF Algotar, Amit M.
Stratton, M. Suzanne
Ahmann, Frederick. R.
Ranger-Moore, James
Nagle, Raymond B.
Thompson, Patricia A.
Slate, Elizabeth
Hsu, Chiu H.
Dalkin, Bruce L.
Sindhwani, Puneet
Holmes, Michael A.
Tuckey, John A.
Graham, David. L.
Parnes, Howard L.
Clark, Lawrence C.
Stratton, Steven P.
TI Phase 3 clinical trial investigating the effect of selenium
supplementation in men at high-risk for prostate cancer
SO PROSTATE
LA English
DT Article
DE prostate cancer; incidence; selenium supplementation
ID PREVENTION TRIAL; NUTRITIONAL PREVENTION; VITAMIN-E; BIOPSIES; SELECT
AB PURPOSE This study was conducted to investigate the effect of Se supplementation on prostate cancer incidence in men at high risk for prostate cancer. METHODS A Phase 3 randomized, double-blind, placebo-controlled clinical trial was conducted in 699 men at high risk for prostate cancer (prostate specific antigen (PSA) >4?ng/ml and/or suspicious digital rectal examination and/or PSA velocity >0.75?ng/ml/year), but with a negative prostate biopsy. Participants were randomized to receive daily oral placebo (N?=?232), 200?mu g selenium (N?=?234), or 400?mu g selenium (N?=?233) as selenized yeast. They were followed every 6 months for up to 5 years. The time to diagnosis of prostate cancer was compared between treatment groups using the Cox proportional hazards model. RESULT Compared to placebo, the hazard ratios [95% confidence intervals] for risk of developing prostate cancer in the selenium 200?mu g/day or the selenium 400?mu g/day group were 0.94 [0.52, 1.7] and 0.90 [0.48, 1.7], respectively. PSA velocity in the selenium arms was not significantly different from that observed in the placebo group (P?=?0.18 and P?=?0.17, respectively). CONCLUSION Selenium supplementation appeared to have no effect on the incidence of prostate cancer in men at high risk. In conjunction with results of other studies, these data indicate that selenium supplementation may not have a role in prostate cancer chemoprevention. Prostate 73: 328335, 2013. (c) 2012 Wiley Periodicals, Inc.
C1 [Algotar, Amit M.; Stratton, M. Suzanne; Ahmann, Frederick. R.; Ranger-Moore, James; Nagle, Raymond B.; Thompson, Patricia A.; Hsu, Chiu H.; Clark, Lawrence C.; Stratton, Steven P.] Univ Arizona, Ctr Canc, Tucson, AZ 85724 USA.
[Ahmann, Frederick. R.; Hsu, Chiu H.] Univ Arizona, Coll Med, Dept Med, Tucson, AZ 85724 USA.
[Ranger-Moore, James; Stratton, Steven P.] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85724 USA.
[Nagle, Raymond B.] Univ Arizona, Coll Med, Dept Pathol, Tucson, AZ 85724 USA.
[Thompson, Patricia A.] Univ Arizona, Coll Med, Dept Anat & Cell Biol, Tucson, AZ 85724 USA.
[Slate, Elizabeth] Med Univ S Carolina, Charleston, SC 29425 USA.
[Dalkin, Bruce L.] Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA.
[Sindhwani, Puneet] Univ Oklahoma, Dept Urol, Oklahoma City, OK USA.
[Holmes, Michael A.] Waikato Hosp, Urol Clin, Hamilton, New Zealand.
[Tuckey, John A.] Auckland Hosp, Auckland, New Zealand.
[Graham, David. L.] Carle Canc Ctr, Urbana, IL USA.
[Parnes, Howard L.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Stratton, SP (reprint author), Univ Arizona, Ctr Canc, POB 245024,1515 N Campbell Ave, Tucson, AZ 85724 USA.
EM sstratton@azcc.arizona.edu
FU National Cancer Institute [PHS CA077789, PHS 023074]
FX Grant sponsor: National Cancer Institute; Grant numbers: PHS CA077789.
PHS 023074.
NR 22
TC 25
Z9 29
U1 1
U2 26
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-4137
J9 PROSTATE
JI Prostate
PD FEB 15
PY 2013
VL 73
IS 3
BP 328
EP 335
DI 10.1002/pros.22573
PG 8
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 075OH
UT WOS:000313895900012
PM 22887343
ER
PT J
AU Hudson, RS
Yi, M
Volfovsky, N
Prueitt, RL
Esposito, D
Volinia, S
Liu, CG
Schetter, AJ
Van Roosbroeck, K
Stephens, RM
Calin, GA
Croce, CM
Ambs, S
AF Hudson, Robert S.
Yi, Ming
Volfovsky, Natalia
Prueitt, Robyn L.
Esposito, Dominic
Volinia, Stefano
Liu, Chang-Gong
Schetter, Aaron J.
Van Roosbroeck, Katrien
Stephens, Robert M.
Calin, George A.
Croce, Carlo M.
Ambs, Stefan
TI Transcription signatures encoded by ultraconserved genomic regions in
human prostate cancer
SO MOLECULAR CANCER
LA English
DT Article
DE Ultraconserved region; Gene expression; Prostate cancer
ID MICRORNA EXPRESSION; DNA METHYLATION; NONCODING RNAS; GENE-EXPRESSION;
ELEMENTS; IDENTIFICATION; NEUROBLASTOMA; REGULATORS; CARCINOMA; TARGETS
AB Background: Ultraconserved regions (UCR) are genomic segments of more than 200 base pairs that are evolutionarily conserved among mammalian species. They are thought to have functions as transcriptional enhancers and regulators of alternative splicing. Recently, it was shown that numerous RNAs are transcribed from these regions. These UCR-encoded transcripts (ucRNAs) were found to be expressed in a tissue- and disease-specific manner and may interfere with the function of other RNAs through RNA: RNA interactions. We hypothesized that ucRNAs have unidentified roles in the pathogenesis of human prostate cancer. In a pilot study, we examined ucRNA expression profiles in human prostate tumors.
Methods: Using a custom microarray with 962 probesets representing sense and antisense sequences for the 481 human UCRs, we examined ucRNA expression in resected, fresh-frozen human prostate tissues (57 tumors, 7 non-cancerous prostate tissues) and in cultured prostate cancer cells treated with either epigenetic drugs (the hypomethylating agent, 5-Aza 2 ' deoxycytidine, and the histone deacetylase inhibitor, trichostatin A) or a synthetic androgen, R1881. Expression of selected ucRNAs was also assessed by qRT-PCR and NanoString (R)-based assays. Because ucRNAs may function as RNAs that target protein-coding genes through direct and inhibitory RNA: RNA interactions, computational analyses were applied to identify candidate ucRNA: mRNA binding pairs.
Results: We observed altered ucRNA expression in prostate cancer (e.g., uc.106+, uc.477+, uc.363 + A, uc.454 + A) and found that these ucRNAs were associated with cancer development, Gleason score, and extraprostatic extension after controlling for false discovery (false discovery rate < 5% for many of the transcripts). We also identified several ucRNAs that were responsive to treatment with either epigenetic drugs or androgen (R1881). For example, experiments with LNCaP human prostate cancer cells showed that uc.287+ is induced by R1881 (P < 0.05) whereas uc.283 + A was up-regulated following treatment with combined 5-Aza 2 ' deoxycytidine and trichostatin A (P < 0.05). Additional computational analyses predicted RNA loop-loop interactions of 302 different sense and antisense ucRNAs with 1058 different mRNAs, inferring possible functions of ucRNAs via direct interactions with mRNAs.
Conclusions: This first study of ucRNA expression in human prostate cancer indicates an altered transcript expression in the disease.
C1 [Hudson, Robert S.; Prueitt, Robyn L.; Schetter, Aaron J.; Ambs, Stefan] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Yi, Ming; Volfovsky, Natalia; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Esposito, Dominic] NCI, Prot Express Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Volinia, Stefano; Croce, Carlo M.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Liu, Chang-Gong; Van Roosbroeck, Katrien; Calin, George A.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 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
OI Volinia, Stefano/0000-0003-0910-3893
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; National Institutes of Health [CA081534,
CA128609]; DPR grant from the Prostate SPORE at the MD Anderson Cancer
Center
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research, and by
National Institutes of Health grants CA081534 and CA128609 (C. M.
Croce). G.A. Calin is supported by a DPR grant from the Prostate SPORE
at the MD Anderson Cancer Center. The authors thank the Cooperative
Prostate Cancer Tissue Resource for providing tissue specimens and
supporting data.
NR 41
TC 19
Z9 19
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD FEB 14
PY 2013
VL 12
AR 13
DI 10.1186/1476-4598-12-13
PG 13
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 123RG
UT WOS:000317407500001
PM 23409773
ER
PT J
AU Bloom-Feshbach, K
Alonso, WJ
Charu, V
Tamerius, J
Simonsen, L
Miller, MA
Viboud, C
AF Bloom-Feshbach, Kimberly
Alonso, Wladimir J.
Charu, Vivek
Tamerius, James
Simonsen, Lone
Miller, Mark A.
Viboud, Cecile
TI Latitudinal Variations in Seasonal Activity of Influenza and Respiratory
Syncytial Virus (RSV): A Global Comparative Review
SO PLOS ONE
LA English
DT Review
ID TRACT INFECTIONS; CLINICAL CHARACTERISTICS; EPIDEMIC INFLUENZA;
ABSOLUTE-HUMIDITY; HONG-KONG; A VIRUS; GROUP-B; CHILDREN; TRANSMISSION;
MORTALITY
AB Background: There is limited information on influenza and respiratory syncytial virus (RSV) seasonal patterns in tropical areas, although there is renewed interest in understanding the seasonal drivers of respiratory viruses.
Methods: We review geographic variations in seasonality of laboratory-confirmed influenza and RSV epidemics in 137 global locations based on literature review and electronic sources. We assessed peak timing and epidemic duration and explored their association with geography and study settings. We fitted time series model to weekly national data available from the WHO influenza surveillance system (FluNet) to further characterize seasonal parameters.
Results: Influenza and RSV activity consistently peaked during winter months in temperate locales, while there was greater diversity in the tropics. Several temperate locations experienced semi-annual influenza activity with peaks occurring in winter and summer. Semi-annual activity was relatively common in tropical areas of Southeast Asia for both viruses. Biennial cycles of RSV activity were identified in Northern Europe. Both viruses exhibited weak latitudinal gradients in the timing of epidemics by hemisphere, with peak timing occurring later in the calendar year with increasing latitude (P < 0.03). Time series model applied to influenza data from 85 countries confirmed the presence of latitudinal gradients in timing, duration, seasonal amplitude, and between-year variability of epidemics. Overall, 80% of tropical locations experienced distinct RSV seasons lasting 6 months or less, while the percentage was 50% for influenza.
Conclusion: Our review combining literature and electronic data sources suggests that a large fraction of tropical locations experience focused seasons of respiratory virus activity in individual years. Information on seasonal patterns remains limited in large undersampled regions, included Africa and Central America. Future studies should attempt to link the observed latitudinal gradients in seasonality of viral epidemics with climatic and population factors, and explore regional differences in disease transmission dynamics and attack rates.
C1 [Bloom-Feshbach, Kimberly; Alonso, Wladimir J.; Charu, Vivek; Simonsen, Lone; Miller, Mark A.; Viboud, Cecile] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Bloom-Feshbach, Kimberly] Mt Sinai Sch Med, New York, NY USA.
[Charu, Vivek] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Tamerius, James] Columbia Univ, Dept Environm Hlth Sci, New York, NY USA.
[Simonsen, Lone] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Global Hlth, Washington, DC USA.
RP Viboud, C (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM viboudc@mail.nih.gov
OI Simonsen, Lone/0000-0003-1535-8526
FU in-house Influenza Research Program of the 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; RAPIDD program
of the Science and Technology Directorate, Department of Homeland
Security
FX 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, and by the RAPIDD program of
the Science and Technology Directorate, Department of Homeland Security
(to L.S.). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 68
TC 64
Z9 66
U1 2
U2 24
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 FEB 14
PY 2013
VL 8
IS 2
AR e54445
DI 10.1371/journal.pone.0054445
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099EJ
UT WOS:000315602700007
PM 23457451
ER
PT J
AU Chen, B
Yi, B
Mao, R
Liu, HT
Wang, JH
Sharma, A
Peiper, S
Leonard, WJ
She, JX
AF Chen, Bo
Yi, Bing
Mao, Rui
Liu, Haitao
Wang, Jinhua
Sharma, Ashok
Peiper, Stephen
Leonard, Warren J.
She, Jin-Xiong
TI Enhanced T Cell Lymphoma in NOD.Stat5b Transgenic Mice Is Caused by
Hyperactivation of Stat5b in CD8(+) Thymocytes
SO PLOS ONE
LA English
DT Article
ID NONOBESE DIABETIC MICE; CONSTITUTIVE ACTIVATION; LYMPHOBLASTIC LYMPHOMA;
UP-REGULATION; JANUS KINASE; DNA-BINDING; NOD MICE; EXPRESSION;
LEUKEMIA; CANCER
AB Activation of signal transducers and activators of transcription (STAT) proteins may be critical to their oncogenic functions as demonstrated by the development of B-cell lymphoma/leukemia in transgenic (TG) mice overexpressing a constitutively activated form of Stat5b. However, low incidence of CD8(+) T cell lymphoma was observed in B6 transgenic mice overexpressing a wild-type Stat5b (B6.Stat5b(Tg)) despite of undetectable Stat5b phosphorylation and the rate of lymphomagenesis was markedly enhanced by immunization or the introduction of TCR transgenes [1]. Here, we report that the wild-type Stat5b transgene leads to the acceleration and high incidence (74%) of CD8(+) T cell lymphoblastic lymphomas in the non-obese-diabetic (NOD) background. In contrast to the B6.Stat5b(Tg) mice, Stat5b in transgenic NOD (NOD.Stat5b(Tg)) mice is selectively and progressively phosphorylated in CD8(+) thymocytes. Stat5 phosphorylation also leads to up-regulation of many genes putatively relevant to tumorigenesis. Treatment of NOD.Stat5b(Tg) mice with cancer chemopreventive agents Apigenin and Xanthohumol efficiently blocked lymphomagenesis through reduction of Stat5 phosphorylation and genes up-regulated in the NOD.Stat5b(Tg) mice. These results suggest that NOD genetic background is critical to the Stat5b-mediated lymphomagenesis through regulation of Stat5 hyperactivation. NOD.Stat5b(Tg) mouse is an excellent model for studying the molecular mechanisms underlying lymphomagenesis and testing novel chemoprevention strategies.
C1 [Chen, Bo; Yi, Bing; Mao, Rui; Liu, Haitao; Wang, Jinhua; Sharma, Ashok; She, Jin-Xiong] Georgia Regents Univ, Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA USA.
[Chen, Bo; Wang, Jinhua; She, Jin-Xiong] Nanjing Univ Technol, Sinoamer Inst Translat Med, Nanjing, Jiangsu, Peoples R China.
[Wang, Jinhua] Jiangsu Canc Hosp, Nanjing, Jiangsu, Peoples R China.
[Peiper, Stephen] Jefferson Univ, Dept Pathol, Philadelphia, PA USA.
[Leonard, Warren J.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP She, JX (reprint author), Georgia Regents Univ, Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA USA.
EM jshe@georgiahealth.edu
RI chen, bo/G-4522-2014
FU Georgia Health Sciences University; National Natural Science Foundation
of China [81272244]; GRA endowment
FX This study was supported by funds from the Georgia Health Sciences
University and National Natural Science Foundation of China(81272244).
J.X.S. is a Georgia Research Alliance (GRA) Eminent Scholar and
supported by a GRA endowment. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 49
TC 4
Z9 4
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 FEB 14
PY 2013
VL 8
IS 2
AR e56600
DI 10.1371/journal.pone.0056600
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099EJ
UT WOS:000315602700084
PM 23457589
ER
PT J
AU Giubellino, A
Sourbier, C
Lee, MJ
Scroggins, B
Bullova, P
Landau, M
Ying, WW
Neckers, L
Trepel, JB
Pacak, K
AF Giubellino, Alessio
Sourbier, Carole
Lee, Min-Jung
Scroggins, Brad
Bullova, Petra
Landau, Michael
Ying, Weiwen
Neckers, Len
Trepel, Jane B.
Pacak, Karel
TI Targeting Heat Shock Protein 90 for the Treatment of Malignant
Pheochromocytoma
SO PLOS ONE
LA English
DT Article
ID MOLECULAR CHAPERONE; HSP90 INHIBITORS; SIGNALING PATHWAYS;
TUMOR-SUPPRESSOR; CANCER-THERAPY; GROWTH-FACTOR; PHASE-I; COMPLEX;
PARAGANGLIOMAS; EXPRESSION
AB Metastatic pheochromocytoma represents one of the major clinical challenges in the field of neuroendocrine oncology. Recent molecular characterization of pheochromocytoma suggests new treatment options with targeted therapies. In this study we investigated the 90 kDa heat shock protein (Hsp90) as a potential therapeutic target for advanced pheochromocytoma. Both the first generation, natural product Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin), and the second-generation synthetic Hsp90 inhibitor STA-9090 (ganetespib) demonstrated potent inhibition of proliferation and migration of pheochromocytoma cell lines and induced degradation of key Hsp90 clients. Furthermore, ganetespib induced dose-dependent cytotoxicity in primary pheochromocytoma cells. Using metastatic models of pheochromocytoma, we demonstrate the efficacy of 17-AAG and ganetespib in reducing metastatic burden and increasing survival. Levels of Hsp70 in plasma from the xenograft studies served as a proximal biomarker of drug treatment. Our study suggests that targeting Hsp90 may benefit patients with advanced pheochromocytoma.
C1 [Giubellino, Alessio; Bullova, Petra; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Sourbier, Carole; Scroggins, Brad; Neckers, Len] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Min-Jung; Landau, Michael; Trepel, Jane B.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Ying, Weiwen] Synta Pharmaceut, Lexington, MA USA.
RP Giubellino, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
EM giubella@mail.nih.gov; karel@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; Center for Cancer Research, National Cancer Institute of
the National Institutes of Health
FX This work was supported by intramural research funding of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
and the Center for Cancer Research, National Cancer Institute of the
National Institutes of Health. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 51
TC 8
Z9 10
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 FEB 14
PY 2013
VL 8
IS 2
AR e56083
DI 10.1371/journal.pone.0056083
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099EJ
UT WOS:000315602700042
PM 23457505
ER
PT J
AU Himes, BE
Sheppard, K
Berndt, A
Leme, AS
Myers, RA
Gignoux, CR
Levin, AM
Gauderman, WJ
Yang, JJ
Mathias, RA
Romieu, I
Torgerson, DG
Roth, LA
Huntsman, S
Eng, C
Klanderman, B
Ziniti, J
Senter-Sylvia, J
Szefler, SJ
Lemanske, RF
Zeiger, RS
Strunk, RC
Martinez, FD
Boushey, H
Chinchilli, VM
Israel, E
Mauger, D
Koppelman, GH
Postma, DS
Nieuwenhuis, MAE
Vonk, JM
Lima, JJ
Irvin, CG
Peters, SP
Kubo, M
Tamari, M
Nakamura, Y
Litonjua, AA
Tantisira, KG
Raby, BA
Bleecker, ER
Meyers, DA
London, SJ
Barnes, KC
Gilliland, FD
Williams, LK
Burchard, EG
Nicolae, DL
Ober, C
DeMeo, DL
Silverman, EK
Paigen, B
Churchill, G
Shapiro, SD
Weiss, ST
AF Himes, Blanca E.
Sheppard, Keith
Berndt, Annerose
Leme, Adriana S.
Myers, Rachel A.
Gignoux, Christopher R.
Levin, Albert M.
Gauderman, W. James
Yang, James J.
Mathias, Rasika A.
Romieu, Isabelle
Torgerson, Dara G.
Roth, Lindsey A.
Huntsman, Scott
Eng, Celeste
Klanderman, Barbara
Ziniti, John
Senter-Sylvia, Jody
Szefler, Stanley J.
Lemanske, Robert F., Jr.
Zeiger, Robert S.
Strunk, Robert C.
Martinez, Fernando D.
Boushey, Homer
Chinchilli, Vernon M.
Israel, Elliot
Mauger, David
Koppelman, Gerard H.
Postma, Dirkje S.
Nieuwenhuis, Maartje A. E.
Vonk, Judith M.
Lima, John J.
Irvin, Charles G.
Peters, Stephen P.
Kubo, Michiaki
Tamari, Mayumi
Nakamura, Yusuke
Litonjua, Augusto A.
Tantisira, Kelan G.
Raby, Benjamin A.
Bleecker, Eugene R.
Meyers, Deborah A.
London, Stephanie J.
Barnes, Kathleen C.
Gilliland, Frank D.
Williams, L. Keoki
Burchard, Esteban G.
Nicolae, Dan L.
Ober, Carole
DeMeo, Dawn L.
Silverman, Edwin K.
Paigen, Beverly
Churchill, Gary
Shapiro, Steve D.
Weiss, Scott T.
TI Integration of Mouse and Human Genome-Wide Association Data Identifies
KCNIP4 as an Asthma Gene
SO PLOS ONE
LA English
DT Article
ID QUANTITATIVE-TRAIT LOCI; INDUCED AIRWAY HYPERRESPONSIVENESS; CHILDHOOD
ASTHMA; SUBSPECIFIC ORIGIN; UNDERLYING ASTHMA; LABORATORY MOUSE; INBRED
MICE; MODEL; SEARCH; POPULATION
AB Asthma is a common chronic respiratory disease characterized by airway hyperresponsiveness (AHR). The genetics of asthma have been widely studied in mouse and human, and homologous genomic regions have been associated with mouse AHR and human asthma-related phenotypes. Our goal was to identify asthma-related genes by integrating AHR associations in mouse with human genome-wide association study (GWAS) data. We used Efficient Mixed Model Association (EMMA) analysis to conduct a GWAS of baseline AHR measures from males and females of 31 mouse strains. Genes near or containing SNPs with EMMA p-values <0.001 were selected for further study in human GWAS. The results of the previously reported EVE consortium asthma GWAS meta-analysis consisting of 12,958 diverse North American subjects from 9 study centers were used to select a subset of homologous genes with evidence of association with asthma in humans. Following validation attempts in three human asthma GWAS (i.e., Sepracor/LOCCS/LODO/Illumina, GABRIEL, DAG) and two human AHR GWAS (i.e., SHARP, DAG), the Kv channel interacting protein 4 (KCNIP4) gene was identified as nominally associated with both asthma and AHR at a gene- and SNP-level. In EVE, the smallest KCNIP4 association was at rs6833065 (P-value 2.9e-04), while the strongest associations for Sepracor/LOCCS/LODO/Illumina, GABRIEL, DAG were 1.5e-03, 1.0e-03, 3.1e-03 at rs7664617, rs4697177, rs4696975, respectively. At a SNP level, the strongest association across all asthma GWAS was at rs4697177 (P-value 1.1e-04). The smallest P-values for association with AHR were 2.3e-03 at rs11947661 in SHARP and 2.1e-03 at rs402802 in DAG. Functional studies are required to validate the potential involvement of KCNIP4 in modulating asthma susceptibility and/or AHR. Our results suggest that a useful approach to identify genes associated with human asthma is to leverage mouse AHR association data.
C1 [Himes, Blanca E.; Ziniti, John; Senter-Sylvia, Jody; Litonjua, Augusto A.; Tantisira, Kelan G.; Raby, Benjamin A.; DeMeo, Dawn L.; Silverman, Edwin K.; Weiss, Scott T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Himes, Blanca E.; Ziniti, John; Senter-Sylvia, Jody; Litonjua, Augusto A.; Tantisira, Kelan G.; Raby, Benjamin A.; DeMeo, Dawn L.; Silverman, Edwin K.; Weiss, Scott T.] Harvard Univ, Sch Med, Boston, MA USA.
[Himes, Blanca E.] Childrens Hosp Informat Program, Boston, MA USA.
[Himes, Blanca E.; Klanderman, Barbara; Weiss, Scott T.] Partners HealthCare Ctr Personalized Genet Med, Boston, MA USA.
[Sheppard, Keith; Paigen, Beverly; Churchill, Gary] Jackson Lab, Bar Harbor, ME 04609 USA.
[Berndt, Annerose; Leme, Adriana S.; Shapiro, Steve D.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA.
[Myers, Rachel A.; Nicolae, Dan L.; Ober, Carole] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Gignoux, Christopher R.; Torgerson, Dara G.; Roth, Lindsey A.; Huntsman, Scott; Eng, Celeste; Burchard, Esteban G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Levin, Albert M.; Yang, James J.] Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA.
[Gauderman, W. James; Gilliland, Frank D.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Mathias, Rasika A.; Barnes, Kathleen C.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Romieu, Isabelle] Int Agcy Res Canc, F-69372 Lyon, France.
[Szefler, Stanley J.] Natl Jewish Hlth, Denver, CO USA.
[Szefler, Stanley J.] Univ Colorado, Denver Sch Med, Denver, CO 80202 USA.
[Lemanske, Robert F., Jr.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Zeiger, Robert S.] Kaiser Permanente Southern Calif Reg, San Diego, CA USA.
[Zeiger, Robert S.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Strunk, Robert C.] Washington Univ, Sch Med, St Louis, MO USA.
[Martinez, Fernando D.] Univ Arizona, Coll Med, Arizona Resp Ctr, Tucson, AZ USA.
[Boushey, Homer] Univ Calif San Francisco, Dept Med, Div Pulm Crit Care & Allergy Immunol, San Francisco, CA USA.
[Chinchilli, Vernon M.; Mauger, David] Penn State Coll Med, Dept Publ Hlth Sci, Hershey, PA USA.
[Israel, Elliot] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Koppelman, Gerard H.] Univ Groningen, Univ Med Ctr Groningen, Dept Pediat Pulmonol & Pediat Allergol, Beatrix Childrens Hosp,GRIAC Res Inst, Groningen, Netherlands.
[Postma, Dirkje S.; Nieuwenhuis, Maartje A. E.] Univ Groningen, Univ Med Ctr Groningen, Dept Pulmonol & TB, GRIAC Res Inst, Groningen, Netherlands.
[Vonk, Judith M.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, GRIAC Res Inst, Groningen, Netherlands.
[Lima, John J.] Ctr Pharmacogen & Translat Res, Nemours Childrens Clin, Jacksonville, FL USA.
[Irvin, Charles G.] Univ Vermont, Dept Physiol & Med, Vermont Lung Ctr, Burlington, VT USA.
[Peters, Stephen P.; Bleecker, Eugene R.; Meyers, Deborah A.] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.
[Kubo, Michiaki; Tamari, Mayumi] RIKEN, Ctr Genom Med, Kanagawa, Japan.
[Nakamura, Yusuke] Univ Tokyo, Inst Med Sci, Mol Med Lab, Tokyo, Japan.
[London, Stephanie J.] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Williams, L. Keoki] Henry Ford Hlth Syst, Ctr Hlth Policy & Hlth Serv Res, Dept Internal Med, Detroit, MI USA.
RP Himes, BE (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
EM blanca.himes@channing.harvard.edu
RI Kubo, Michiaki/N-7947-2015; Tamari, Mayumi/N-5378-2015;
OI Litonjua, Augusto/0000-0003-0422-5875; London,
Stephanie/0000-0003-4911-5290
FU NHLBI, National Institutes of Health (NIH) [U01 HL075419, U01 HL65899,
P01 HL083069, R01 HL086601, T32 HL07427]; NIH [U01 HL65899, U10
HL064287, U10 HL064288, U10 HL064295, U10 HL064305, U10 HL064307, U01
HL064313, RC2 HL101487, R01 HL087699, K99 HL105663]; NIH
Pharmacogenomics Research Network (PGRN) - RIKEN Center for Genomic
Medicine (CGM) Global Alliance; BioBank Japan project; Ministry of
Education, Culture, Sports, Sciences and Technology of the Japanese
government; American Asthma Foundation; Fund for Henry Ford Hospital;
NIH from the National Institute of Allergy and Infectious Diseases
(NIAID) [R01AI079139, R01AI061774]; Mary Beryl Patch Turnbull Scholar
Program; Division of Intramural Research, National Institute of
Environmental Health Sciences; Netherlands Asthma Foundation grant AF
[AF 95.09, AF 98.48, AF 3.2.02.51, AF 3.2.07.015]; University Medical
Center Groningen; Ter Meulen Fund grant from the Royal Netherlands
Academy of Arts and Sciences; Royal Netherlands Academy of Arts and
Sciences Honorary Professorship; National Heart, Lung and Blood
Institute (NHLBI)
FX The CAMP Genetics Ancillary Study is supported by U01 HL075419, U01
HL65899, P01 HL083069, R01 HL086601, and T32 HL07427 from the NHLBI,
National Institutes of Health (NIH). Additional support was provided by
NIH U10 HL064287, U10 HL064288, U10 HL064295, U10 HL064305, U10
HL064307, U01 HL064313, RC2 HL101487, R01 HL087699 and U01 HL65899, an
NIH Pharmacogenomics Research Network (PGRN) - RIKEN Center for Genomic
Medicine (CGM) Global Alliance and by funding from the BioBank Japan
project that was supported by the Ministry of Education, Culture,
Sports, Sciences and Technology of the Japanese government. We thank the
American Lung Association Asthma Clinical Research Centers (ALA-ACRC)
for use of LOCCS and LODO study samples. B.E.H. was supported by NIH K99
HL105663. L.K.W. is funded by the American Asthma Foundation, the Fund
for Henry Ford Hospital, and by NIH R01AI079139 and R01AI061774 from the
National Institute of Allergy and Infectious Diseases (NIAID). K.C.B.
was supported in part by the Mary Beryl Patch Turnbull Scholar Program.
S.J.L. is supported by the Division of Intramural Research, National
Institute of Environmental Health Sciences. D.A.G. was supported by the
Netherlands Asthma Foundation grant AF (AF 95.09, AF 98.48, AF 3.2.02.51
and AF 3.2.07.015) and a grant from the University Medical Center
Groningen. GHK was supported by a Ter Meulen Fund grant from the Royal
Netherlands Academy of Arts and Sciences. D.S.P. was supported by a
Royal Netherlands Academy of Arts and Sciences Honorary Professorship.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.; We thank all
CAMP subjects for their ongoing participation in this study. We
acknowledge the CAMP investigators and research team, supported by the
National Heart, Lung and Blood Institute (NHLBI), for collection of CAMP
Genetic Ancillary Study data. All work on data collected from the CAMP
Genetic Ancillary Study was conducted at the Channing Laboratory of the
Brigham and Women's Hospital under appropriate CAMP policies and human
subject's protections. We acknowledge the following GALA 1
investigators: Michael A. LeNoir, MD (Bay Area Pediatrics, Oakland, CA,
USA), Harold J. Farber, MD (Section of Pulmonology, Baylor College of
Medicine, Houston, TX, USA), Rajesh Kumar, MD, MPH (Division of Allergy
and Immunology, Children's Memorial Hospital, Chicago, IL, USA), Pedro
C. Avila, MD (Department of Medicine, Northwestern University, Chicago,
IL, USA), Kelley Meade, MD (Children's Hospital of Oakland, Oakland, CA,
USA), Denise Serebrisky, MD (Jacobi Medical Center and Department of
Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA),
Shannon Thyne, MD (Department of Medicine, University of California, San
Francisco, San Francisco, CA, USA), William Rodriguez-Cintron, MD
(Veterans Affairs Medical Center, San Juan, Puerto Rico), Jose R.
Rodriguez-Santana, MD (Centro de Neumologia Pediatrica, San Juan, Puerto
Rico), Luisa N. Borrell, DDS, PhD (Department of Health Sciences, Lehman
College, City University of New York, New York, NY, USA).
NR 57
TC 16
Z9 18
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 FEB 14
PY 2013
VL 8
IS 2
AR e56179
DI 10.1371/journal.pone.0056179
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099EJ
UT WOS:000315602700056
PM 23457522
ER
PT J
AU Wongtrakoongate, P
Jones, M
Gokhale, PJ
Andrews, PW
AF Wongtrakoongate, Patompon
Jones, Mark
Gokhale, Paul J.
Andrews, Peter W.
TI STELLA Facilitates Differentiation of Germ Cell and Endodermal Lineages
of Human Embryonic Stem Cells
SO PLOS ONE
LA English
DT Article
ID DNA DEMETHYLATION; IN-VITRO; EXPRESSION PATTERNS; LINES; CULTURE;
TUMORS; SPECIFICATION; ADAPTATION; DERIVATION; DEAMINASE
AB Stella is a developmentally regulated gene highly expressed in mouse embryonic stem (ES) cells and in primordial germ cells (PGCs). In human, the gene encoding the STELLA homologue lies on chromosome 12p, which is frequently amplified in long-term cultured human ES cells. However, the role played by STELLA in human ES cells has not been reported. In the present study, we show that during retinoic acid (RA)-induced differentiation of human ES cells, expression of STELLA follows that of VASA, a marker of germline differentiation. By contrast, human embryonal carcinoma cells express STELLA at a higher level compared with both karyotypically normal and abnormal human ES cell lines. We found that over-expression of STELLA does not interfere with maintenance of the stem cell state of human ES cells, but following retinoic acid induction it leads to up-regulation of germline- and endodermal-associated genes, whereas neural markers PAX6 and NEUROD1 are down-regulated. Further, STELLA over-expression facilitates the differentiation of human ES cells into BE12-positive cells, in which the expression of germline- and endodermal-associated genes is enriched, and suppresses differentiation of the neural lineage. Taken together, this finding suggests a role for STELLA in facilitating germline and endodermal differentiation of human ES cells.
C1 [Wongtrakoongate, Patompon; Jones, Mark; Gokhale, Paul J.; Andrews, Peter W.] Univ Sheffield, Dept Biomed Sci, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England.
RP Wongtrakoongate, P (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM p.wongtrakoongate@gmail.com; p.w.andrews@sheffield.ac.uk
OI Gokhale, Paul/0000-0001-7225-4403
FU Thai government; Royal Thai Government; Medical Research Council
FX PW is a PhD student supported by the Thai government. This work was
supported by the Royal Thai Government. PWA is supported by a grant from
the Medical Research Council. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 39
TC 16
Z9 19
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 FEB 14
PY 2013
VL 8
IS 2
AR e56893
DI 10.1371/journal.pone.0056893
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099EJ
UT WOS:000315602700101
PM 23457636
ER
PT J
AU Kumar, TS
Yang, T
Mishra, S
Cronin, C
Chakraborty, S
Shen, JB
Liang, BT
Jacobson, KA
AF Kumar, T. Santhosh
Yang, Tiehong
Mishra, Shilpi
Cronin, Chunxia
Chakraborty, Saibal
Shen, Jian-Bing
Liang, Bruce T.
Jacobson, Kenneth A.
TI 5 '-Phosphate and 5 '-Phosphonate Ester Derivatives of (N)-Methanocarba
Adenosine with in Vivo Cardioprotective Activity
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID HEART-FAILURE; P2X RECEPTOR; STABILITY; PRODRUGS; ANALOGS;
CARDIOMYOPATHY; CONFORMATION; ACTIVATION; MYOCYTES; RESCUE
AB Activation of a cardiac myocyte P2X4 receptor protects against heart failure. 5'-Phosphonate and 5'-phosphate analogues of AMP containing a (N)-methanocarba (bicyclo[3.1.0]hexane) system could protect from heart failure by potentially activating this cardioprotective channel. Phosphoesters and phosphonodiesters were synthesized and administered in vivo via a miniosmotic pump in a mouse ischemic heart failure model and most significantly increased intact heart contractile function (echocardiography) compared to vehicle were protective in a calsequestrin (CSQ) overexpressing heart infusion. Several new thio and deuterated phosphate derivatives failure model. Diethyl (7, MRS4084) and diisopropyl (8, MRS4074) phosphotriesters were highly protective in the ischemic model. Substitution of 2-Cl with iodo reduced protection in the CSQ model. Diisopropyl ester 16 (MRS2978) of (1'S,2'R,3'S,4'R,5'S)-4'-(6-amino-2-chloropurin-9-yl)-2',3'-(dihydroxy)-1'-(phosphonoethylene)bicyclo[3.1.0]hexane was highly efficacious (CSQ), while lower homologue 1'-phosphonomethylene derivative 14 was inactive. Thus, we identified undiarged carbocyclic nucleotide analogues that represent potential candidates for the treatment of heart failure, suggesting this as a viable and structurally broad approach.
C1 [Kumar, T. Santhosh; Mishra, Shilpi; Chakraborty, Saibal; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA.
[Yang, Tiehong; Cronin, Chunxia; Shen, Jian-Bing; Liang, Bruce T.] Univ Connecticut, Ctr Hlth, Pat & Jim Calhoun Cardiol Ctr, Farmington, CT 06030 USA.
RP Jacobson, KA (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Intramural Research Program of the NIH, National Institute of Diabetes
and Digestive and Kidney Diseases; Ray Neag Distinguished Professorship;
[RO1-HL48225]
FX Mass spectral measurements were carried out by Dr. John Lloyd and Dr.
Noel Whittaker (NIDDK). This research was supported in part by the
Intramural Research Program of the NIH, National Institute of Diabetes
and Digestive and Kidney Diseases. This work was supported in part by
Grant RO1-HL48225 and Ray Neag Distinguished Professorship to Bruce T.
Liang.
NR 23
TC 13
Z9 13
U1 0
U2 6
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 FEB 14
PY 2013
VL 56
IS 3
BP 902
EP 914
DI 10.1021/jm301372c
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 093HK
UT WOS:000315182100024
PM 23286881
ER
PT J
AU Cui, GH
Jun, SB
Jin, X
Pham, MD
Vogel, SS
Lovinger, DM
Costa, RM
AF Cui, Guohong
Jun, Sang Beom
Jin, Xin
Pham, Michael D.
Vogel, Steven S.
Lovinger, David M.
Costa, Rui M.
TI Concurrent activation of striatal direct and indirect pathways during
action initiation
SO NATURE
LA English
DT Article
ID IMAGING IN-VIVO; BASAL GANGLIA; STRIATOPALLIDAL NEURONS; MOTOR
BEHAVIORS; POPULATIONS; DISORDERS; MOVEMENTS; RESPONSES; CIRCUITS; MOUSE
AB The basal ganglia are subcortical nuclei that control voluntary actions, and they are affected by a number of debilitating neurological disorders(1-4). The prevailing model of basal ganglia function proposes that two orthogonal projection circuits originating from distinct populations of spiny projection neurons (SPNs) in the striatum(5,6)-the so-called direct and indirect pathways have opposing effects on movement: activity of direct-pathway SPNs is thought to facilitate movement, whereas activity of indirect-pathway SPNs is presumed to inhibit movement(1,2). This model has been difficult to test owing to the lack of methods to selectively measure the activity of direct- and indirect-pathway SPNs in freely moving animals: Here we develop a novel in vivo method to specifically measure direct- and indirect-pathway SPN activity, using Cre-dependent viral expression of the genetically encoded calcium indicator (GECI) GCaMP3 in the dorsal striatum of D1-Cre (direct-pathway-specific(6,7)) and A2A-Cre (indirect-pathway-specific(8,9)) mice. Using fibre optics and time-correlated single-photon counting (TCSPC) in mice performing an operant task, we observed transient-increases in neural activity in both direct- and indirect-pathway SPNs when animals initiated actions, but not when they were inactive. Concurrent activation of SPNs from both pathways in one hemisphere preceded the initiation of contraversive movements and predicted the occurrence of specific movements within 500 ms. These observations challenge the classical view of basal ganglia function and may have implications for understanding the origin of motor symptoms in basal ganglia disorders.
C1 [Cui, Guohong; Jin, Xin; Pham, Michael D.; Lovinger, David M.; Costa, Rui M.] NIAAA, Sect Vivo Neural Funct, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
[Jun, Sang Beom] Ewha Womans Univ, Dept Elect Engn, Seoul 120750, South Korea.
[Jin, Xin] Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA.
[Vogel, Steven S.] NIAAA, Sect Cellular Biophoton, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
[Lovinger, David M.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
[Costa, Rui M.] Inst Gulbenkian Ciencias, Champalimaud Neurosci Programme, P-1400038 Lisbon, Portugal.
[Costa, Rui M.] Champalimaud Ctr Unknown, P-1400038 Lisbon, Portugal.
RP Vogel, SS (reprint author), NIAAA, Sect Cellular Biophoton, Lab Mol Physiol, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM stevevog@mail.nih.gov; lovindav@mail.nih.gov; ruicosta@fchampalimaud.org
OI Vogel, Steven/0000-0002-3005-2667; Costa, Rui/0000-0003-0495-8374
FU Division of Intramural Clinical and Biological Research of the NIAAA;
European Research Council [STG 243393]; International Early Career
Scientist grant from the Howard Hughes Medical Institute; National
Research Foundation of Korea [2011-0029485, 2012-0004003]; SmartIT
Convergence System Research Center from the Korean government (MEST)
[SIRC-2011-0031866]; Ellison Medical Foundation [AG-NS-0944-12]
FX We thank C. R. Gerfen for gifts of multiple bacterial artificial
chromosome (BAC) transgenic mouse lines; L. L. Looger and the Howard
Hughes Medical Institute (HHMI) for permission to use AAV GCaMP3 vectors
and GCaMP3 mice; S. R. Ikeda for assistance with Ca2+ imaging
in brain slices; G. Luo for mouse genotyping; C. Thaler for assistance
with FLIM curve analysis; B. Mathur and M. Davis for assistance with
brain slice electrophysiology and histology; and A. Martin for
assistance with AAV vector injection. This work was supported by the
Division of Intramural Clinical and Biological Research of the NIAAA,
European Research Council STG 243393, an International Early Career
Scientist grant from the Howard Hughes Medical Institute to R.M.C., a
National Research Foundation of Korea grant (2011-0029485,2012-0004003)
and SmartIT Convergence System Research Center (SIRC-2011-0031866) from
the Korean government (MEST) to S.B.J., and by an Ellison Medical
Foundation grant (AG-NS-0944-12) to X.J.
NR 30
TC 235
Z9 237
U1 9
U2 85
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD FEB 14
PY 2013
VL 494
IS 7436
BP 238
EP 242
DI 10.1038/nature11846
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700040
PM 23354054
ER
PT J
AU Haso, W
Lee, DW
Shah, NN
Stetler-Stevenson, M
Yuan, CM
Pastan, IH
Dimitrov, DS
Morgan, RA
FitzGerald, DJ
Barrett, DM
Wayne, AS
Mackall, CL
Orentas, RJ
AF Haso, Waleed
Lee, Daniel W.
Shah, Nirali N.
Stetler-Stevenson, Maryalice
Yuan, Constance M.
Pastan, Ira H.
Dimitrov, Dimiter S.
Morgan, Richard A.
FitzGerald, David J.
Barrett, David M.
Wayne, Alan S.
Mackall, Crystal L.
Orentas, Rimas J.
TI Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute
lymphoblastic leukemia
SO BLOOD
LA English
DT Article
ID T-CELLS; HEMATOLOGIC MALIGNANCIES; ANTITUMOR-ACTIVITY; RECOMBINANT
IMMUNOTOXIN; SIGNAL-TRANSDUCTION; CHIMERIC RECEPTORS; CYTOTOXIC
ACTIVITY; ENHANCED SURVIVAL; FLOW-CYTOMETRY; CLINICAL-TRIAL
AB Immune targeting of B-cell malignancies using chimeric antigen receptors (CARs) is a promising new approach, but critical factors impacting CAR efficacy remain unclear. To test the suitability of targeting CD22 on precursor B-cell acute lymphoblastic leukemia (BCP-ALL), lymphoblasts from 111 patients with BCP-ALL were assayed for CD22 expression and all were found to be CD22-positive, with median CD22 expression levels of 3500 sites/cell. Three distinct binding domains targeting CD22 were fused to various TCR signaling domains +/- an IgG heavy chain constant domain (CH2CH3) to create a series of vector constructs suitable to delineate optimal CAR configuration. CARs derived from the m971 anti-CD22 mAb, which targets a proximal CD22 epitope demonstrated superior antileukemic activity compared with those incorporating other binding domains, and addition of a 4-1BB signaling domain to CD28. CD3 zeta constructs diminished potency, whereas increasing affinity of the anti-CD22 binding motif, and extending the CD22 binding domain away from the membrane via CH2CH3 had no effect. We conclude that second-generation m971 mAb-derived anti-CD22 CARs are promising novel therapeutics that should be tested in BCP-ALL. (Blood. 2013; 121(7): 1165-1174)
C1 [Haso, Waleed; Lee, Daniel W.; Shah, Nirali N.; Wayne, Alan S.; Mackall, Crystal L.; Orentas, Rimas J.] NCI, Pediat Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA.
[Stetler-Stevenson, Maryalice; Yuan, Constance M.] NCI, Pathol Lab, CCR, NIH, Bethesda, MD 20892 USA.
[Pastan, Ira H.; FitzGerald, David J.; Wayne, Alan S.] NCI, Mol Biol Lab, CCR, NIH, Bethesda, MD 20892 USA.
[Dimitrov, Dimiter S.] Frederick Natl Lab, CCR Nanobiol Program, Frederick, MD USA.
[Morgan, Richard A.] NCI, Surg Branch, CCR, NIH, Bethesda, MD 20892 USA.
[Barrett, David M.] Univ Penn, Perelman Sch Med, Childrens Hosp Penn, Blood & Marrow Transplantat Program, Philadelphia, PA 19104 USA.
RP Orentas, RJ (reprint author), NCI, Pediat Oncol Branch, CCR, NIH, 10 Ctr Dr,1W3840, Bethesda, MD 20892 USA.
EM rimas.orentas@nih.gov
FU NIH, CCR, NCI
FX This research was supported by the Intramural Research Program of the
NIH, CCR, NCI.
NR 39
TC 115
Z9 119
U1 0
U2 25
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 FEB 14
PY 2013
VL 121
IS 7
BP 1165
EP 1174
DI 10.1182/blood-2012-06-438002
PG 10
WC Hematology
SC Hematology
GA 088XH
UT WOS:000314870700020
PM 23243285
ER
PT J
AU Ren, XF
Farias, GG
Canagarajah, BJ
Bonifacino, JS
Hurley, JH
AF Ren, Xuefeng
Farias, Ginny G.
Canagarajah, Bertram J.
Bonifacino, Juan S.
Hurley, James H.
TI Structural Basis for Recruitment and Activation of the AP-1 Clathrin
Adaptor Complex by Arf1
SO CELL
LA English
DT Article
ID ADP-RIBOSYLATION FACTOR; CARGO-SORTING SIGNALS; GTP-BINDING PROTEIN;
COATED VESICLES; MEMBRANE RECRUITMENT; GOLGI MEMBRANES; AP2 COMPLEX;
HIV-1 NEF; RECOGNITION; SUBUNIT
AB AP-1 is a clathrin adaptor complex that sorts cargo between the trans-Golgi network and endosomes. AP-1 recruitment to these compartments requires Arf1-GTP. The crystal structure of the tetrameric core of AP-1 in complex with Arf1-GTP, together with biochemical analyses, shows that Arf1 activates cargo binding by unlocking AP-1. Unlocking is driven by two molecules of Arf1 that bridge two copies of AP-1 at two interaction sites. The GTP-dependent switch I and II regions of Arf1 bind to the N terminus of the beta 1 subunit of one AP-1 complex, while the back side of Arf1 binds to the central part of the gamma subunit trunk of a second AP-1 complex. A third Arf1 interaction site near the N terminus of the gamma subunit is important for recruitment, but not activation. These observations lead to a model for the recruitment and activation of AP-1 by Arf1.
C1 [Ren, Xuefeng; Farias, Ginny G.; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Canagarajah, Bertram J.; Hurley, James H.] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM bonifacinoj@helix.nih.gov; james.hurley@nih.gov
OI Bonifacino, Juan S./0000-0002-5673-6370
FU U. S. Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-31-109-Eng-38]; NICHD; NIDDK, NIH
FX We thank G. Mardones for assistance with constructs and W. Yang for
critically reading the manuscript. Crystallographic data were collected
at Southeast Regional Collaborative Access Team 22-ID beamline at the
Advanced Photon Source, Argonne National Laboratory. Use of the Advanced
Photon Source 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 research was supported by the Intramural Programs
of NICHD (J.S.B.) and NIDDK (J.H.H.), NIH.
NR 48
TC 48
Z9 48
U1 1
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD FEB 14
PY 2013
VL 152
IS 4
BP 755
EP 767
DI 10.1016/j.cell.2012.12.042
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 089YJ
UT WOS:000314945600011
PM 23415225
ER
PT J
AU Visel, A
Taher, L
Girgis, H
May, D
Golonzhka, O
Hoch, RV
McKinsey, GL
Pattabiraman, K
Silberberg, SN
Blow, MJ
Hansen, DV
Nord, AS
Akiyama, JA
Holt, A
Hosseini, R
Phouanenavong, S
Plajzer-Frick, I
Shoukry, M
Afzal, V
Kaplan, T
Kriegstein, AR
Rubin, EM
Ovcharenko, I
Pennacchio, LA
Rubenstein, JLR
AF Visel, Axel
Taher, Leila
Girgis, Hani
May, Dalit
Golonzhka, Olga
Hoch, Renee V.
McKinsey, Gabriel L.
Pattabiraman, Kartik
Silberberg, Shanni N.
Blow, Matthew J.
Hansen, David V.
Nord, Alex S.
Akiyama, Jennifer A.
Holt, Amy
Hosseini, Roya
Phouanenavong, Sengthavy
Plajzer-Frick, Ingrid
Shoukry, Malak
Afzal, Veena
Kaplan, Tommy
Kriegstein, Arnold R.
Rubin, Edward M.
Ovcharenko, Ivan
Pennacchio, Len A.
Rubenstein, John L. R.
TI A High-Resolution Enhancer Atlas of the Developing Telencephalon
SO CELL
LA English
DT Article
ID TRANSCRIPTION FACTOR-BINDING; RECOMBINASE ACTIVITY; BRAIN-DEVELOPMENT;
RANDOM FORESTS; EXPRESSION; SCHIZOPHRENIA; DATABASE; AUTISM;
CHROMOSOMES; ASSOCIATION
AB The mammalian telencephalon plays critical roles in cognition, motor function, and emotion. Though many of the genes required for its development have been identified, the distant-acting regulatory sequences orchestrating their in vivo expression are mostly unknown. Here, we describe a digital atlas of in vivo enhancers active in subregions of the developing telencephalon. We identified more than 4,600 candidate embryonic forebrain enhancers and studied the in vivo activity of 329 of these sequences in transgenic mouse embryos. We generated serial sets of histological brain sections for 145 reproducible forebrain enhancers, resulting in a publicly accessible web-based data collection comprising more than 32,000 sections. We also used epigenomic analysis of human and mouse cortex tissue to directly compare the genome-wide enhancer architecture in these species. These data provide a primary resource for investigating gene regulatory mechanisms of telencephalon development and enable studies of the role of distant-acting enhancers in neurodevelopmental disorders.
C1 [Visel, Axel; May, Dalit; Nord, Alex S.; Akiyama, Jennifer A.; Holt, Amy; Hosseini, Roya; Phouanenavong, Sengthavy; Plajzer-Frick, Ingrid; Shoukry, Malak; Afzal, Veena; Rubin, Edward M.; Pennacchio, Len A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA.
[Visel, Axel; Blow, Matthew J.; Rubin, Edward M.; Pennacchio, Len A.] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.
[Taher, Leila; Girgis, Hani; Ovcharenko, Ivan] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Golonzhka, Olga; Hoch, Renee V.; McKinsey, Gabriel L.; Pattabiraman, Kartik; Silberberg, Shanni N.; Rubenstein, John L. R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94158 USA.
[Hansen, David V.; Kriegstein, Arnold R.] Univ Calif San Francisco, Eli & Edythe Broad, Ctr Regenerat Med & Stem Cell Res, San Francisco, CA 94143 USA.
[Hansen, David V.; Kriegstein, Arnold R.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Kaplan, Tommy] Univ Calif Berkeley, Calif Inst Quantitat Biosci, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Kaplan, Tommy] Hebrew Univ Jerusalem, Sch Comp Sci & Engn, IL-91904 Jerusalem, Israel.
RP Visel, A (reprint author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, MS 84-171, Berkeley, CA 94720 USA.
EM avisel@lbl.gov
RI Visel, Axel/A-9398-2009; Blow, Matthew/G-6369-2012;
OI Visel, Axel/0000-0002-4130-7784; Blow, Matthew/0000-0002-8844-9149;
Hansen, David/0000-0001-9679-7189; Hoch, Renee/0000-0003-0042-3751
FU NINDS [R01NS062859A, R01NS34661, R01NS075998]; NHGRI [R01HG003988]; Nina
Ireland; Weston Havens Foundation; NIMH [R01MH081880, R37MH049428]; CIRM
[RB2-1602]; NARSAD; Intramural Research Program of the NIH; National
Library of Medicine; Department of Energy [DE-AC02-05CH11231]; [T32
GM007449]; [T32 GMO7618]; [F32 MH081431]
FX The authors thank Julian Golder and Noah Efron for help with digital
image acquisition and data processing; Bing Ren and Zirong Li for help
with chromatin immunoprecipitation from embryonic mouse tissue; Inna
Dubchak, Simon Minovitsky, and Alexandre Poliakov for website support;
and staff at San Francisco General Hospital Women's Options Center for
their consideration in allowing us to access donated fetal tissue. A.V.
and L.A.P. were supported by NINDS grant R01NS062859A and by NHGRI grant
R01HG003988. J.L.R.R. was supported by the Nina Ireland, Weston Havens
Foundation, NINDS grant R01NS34661, NIMH grant R01MH081880, and NIMH
grant R37MH049428. J.L.R.R. and A.R.K were supported by CIRM RB2-1602.
G.M. and S.N.S. were supported by T32 GM007449, K.P. was supported by
T32 GMO7618, R.H. was supported by F32 MH081431, and O.G. was supported
by NARSAD. A.R.K. was supported by NINDS grant R01NS075998. I.O. was
supported by the Intramural Research Program of the NIH, National
Library of Medicine. Research was conducted at the E.O. Lawrence
Berkeley National Laboratory and performed under Department of Energy
Contract DE-AC02-05CH11231, University of California.
NR 55
TC 87
Z9 87
U1 0
U2 32
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD FEB 14
PY 2013
VL 152
IS 4
BP 895
EP 908
DI 10.1016/j.cell.2012.12.041
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 089YJ
UT WOS:000314945600022
PM 23375746
ER
PT J
AU Berezhkovskii, AM
Dagdug, L
Vazquez, MV
Lizunov, VA
Zimmerberg, J
Bezrukov, SM
AF Berezhkovskii, Alexander M.
Dagdug, Leonardo
Vazquez, Marco-Vinicio
Lizunov, Vladimir A.
Zimmerberg, Joshua
Bezrukov, Sergey M.
TI Trapping of diffusing particles by clusters of absorbing disks on a
reflecting wall with disk centers on sites of a square lattice
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID 1ST PASSAGE TIME; LIGAND-BINDING; LIPID RAFTS; ASYMPTOTIC ANALYSIS;
CELL-MEMBRANES; RATE CONSTANTS; RECEPTORS; SURFACES
AB A simple approximate formula is derived for the rate constant that describes steady-state flux of diffusing particles through a cluster of perfectly absorbing disks on the otherwise reflecting flat wall, assuming that the disk centers occupy neighboring sites of a square lattice. A distinctive feature of trapping by a disk cluster is that disks located at the cluster periphery shield the disks in the center of the cluster. This competition of the disks for diffusing particles makes it impossible to find an exact analytical solution for the rate constant in the general case. To derive the approximate formula, we use a recently suggested approach [A. M. Berezhkovskii, L. Dagdug, V. A. Lizunov, J. Zimmerberg, and S. M. Bezrukov, J. Chem. Phys. 136, 211102 (2012)], which is based on the replacement of the disk cluster by an effective uniform partially absorbing spot. The formula shows how the rate constant depends on the size and shape of the cluster. To check the accuracy of the formula, we compare its predictions with the values of the rate constant obtained from Brownian dynamics simulations. The comparison made for 18 clusters of various shapes and sizes shows good agreement between the theoretical predictions and numerical results. (C) 2013 American Institute of Physics. [http://dx.doi.org/10.1063/1.4790370]
C1 [Berezhkovskii, Alexander M.; Dagdug, Leonardo] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Berezhkovskii, Alexander M.; Dagdug, Leonardo; Lizunov, Vladimir A.; Zimmerberg, Joshua; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Dagdug, Leonardo; Vazquez, Marco-Vinicio] Univ Autonoma Metropolitana, Dept Fis, Mexico City 09340, DF, Mexico.
RP Berezhkovskii, AM (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
RI Lizunov, Vladimir/B-5468-2009
FU National Institutes of Health (NIH), Center for Information Technology;
Eunice Kennedy Shriver National Institute of Child Health and Human
Development; CONACyT [176452]
FX We are grateful to Super Computer Division of Universidad Autonoma
Metropolitana-Iztapalapa for the use of their computational facilities.
This study was supported by the Intramural Research Program of the
National Institutes of Health (NIH), Center for Information Technology
and Eunice Kennedy Shriver National Institute of Child Health and Human
Development and partially supported by CONACyT under Grant No. 176452.
NR 32
TC 1
Z9 1
U1 0
U2 5
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
EI 1089-7690
J9 J CHEM PHYS
JI J. Chem. Phys.
PD FEB 14
PY 2013
VL 138
IS 6
AR 064105
DI 10.1063/1.4790370
PG 6
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 091MS
UT WOS:000315054400009
ER
PT J
AU Buckley, DM
Burroughs-Garcia, J
Lewandoski, M
Waters, ST
AF Buckley, Desire M.
Burroughs-Garcia, Jessica
Lewandoski, Mark
Waters, Samuel T.
TI Characterization of the Gbx1(-/-) Mouse Mutant: A Requirement for Gbx1
in Normal Locomotion and Sensorimotor Circuit Development
SO PLOS ONE
LA English
DT Article
ID DORSAL SPINAL-CORD; MOTOR-NEURON IDENTITY; ROOT GANGLION NEURONS;
MID/HINDBRAIN ORGANIZER; TRANSCRIPTIONAL CODES; SUBTYPE IDENTITY;
NERVOUS-SYSTEM; GENE-FUNCTION; SPECIFICATION; EXPRESSION
AB The Gbx class of homeobox genes encodes DNA binding transcription factors involved in regulation of embryonic central nervous system (CNS) development. Gbx1 is dynamically expressed within spinal neuron progenitor pools and becomes restricted to the dorsal mantle zone by embryonic day (E) 12.5. Here, we provide the first functional analysis of Gbx1. We generated mice containing a conditional Gbx1 allele in which exon 2 that contains the functional homeodomain is flanked with loxP sites (Gbx1(flox)); Cre-mediated recombination of this allele results in a Gbx1 null allele. In contrast to mice homozygous for a loss-of-function allele of Gbx2, mice homozygous for the Gbx1 null allele, Gbx1(-/-), are viable and reproductively competent. However, Gbx1(-/-) mice display a gross locomotive defect that specifically affects hindlimb gait. Analysis of embryos homozygous for the Gbx1 null allele reveals disrupted assembly of the proprioceptive sensorimotor circuit within the spinal cord, and a reduction in ISL1(+) ventral motor neurons. These data suggest a functional requirement for Gbx1 in normal development of the neural networks that contribute to locomotion. The generation of this null allele has enabled us to functionally characterize a novel role for Gbx1 in development of the spinal cord.
C1 [Buckley, Desire M.; Burroughs-Garcia, Jessica; Waters, Samuel T.] Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA.
[Buckley, Desire M.; Burroughs-Garcia, Jessica; Waters, Samuel T.] Univ Missouri, Christopher S Bond Life Sci Ctr, Columbia, MO USA.
[Lewandoski, Mark] NCI, Canc & Dev Biol Lab, NIH, Frederick, MD 21701 USA.
RP Waters, ST (reprint author), Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA.
EM waterssa@missouri.edu
FU University of Missouri; National Science Foundation [1021288]
FX This work was supported by startup funds from the University of Missouri
(STW) and by the National Science Foundation award 1021288. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 59
TC 5
Z9 5
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 FEB 13
PY 2013
VL 8
IS 2
AR e56214
DI 10.1371/journal.pone.0056214
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 104DM
UT WOS:000315970300128
PM 23418536
ER
PT J
AU Gaughan, AE
Stevens, FR
Linard, C
Jia, P
Tatem, AJ
AF Gaughan, Andrea E.
Stevens, Forrest R.
Linard, Catherine
Jia, Peng
Tatem, Andrew J.
TI High Resolution Population Distribution Maps for Southeast Asia in 2010
and 2015
SO PLOS ONE
LA English
DT Article
ID LAND-COVER; ACCURACY; CENSUS; HEALTH; RISK
AB Spatially accurate, contemporary data on human population distributions are vitally important to many applied and theoretical researchers. The Southeast Asia region has undergone rapid urbanization and population growth over the past decade, yet existing spatial population distribution datasets covering the region are based principally on population count data from censuses circa 2000, with often insufficient spatial resolution or input data to map settlements precisely. Here we outline approaches to construct a database of GIS-linked circa 2010 census data and methods used to construct fine-scale (similar to 100 meters spatial resolution) population distribution datasets for each country in the Southeast Asia region. Landsat-derived settlement maps and land cover information were combined with ancillary datasets on infrastructure to model population distributions for 2010 and 2015. These products were compared with those from two other methods used to construct commonly used global population datasets. Results indicate mapping accuracies are consistently higher when incorporating land cover and settlement information into the AsiaPop modelling process. Using existing data, it is possible to produce detailed, contemporary and easily updatable population distribution datasets for Southeast Asia. The 2010 and 2015 datasets produced are freely available as a product of the AsiaPop Project and can be downloaded from: www.asiapop.org.
C1 [Gaughan, Andrea E.; Stevens, Forrest R.; Jia, Peng; Tatem, Andrew J.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Gaughan, Andrea E.; Stevens, Forrest R.; Jia, Peng; Tatem, Andrew J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA.
[Gaughan, Andrea E.; Stevens, Forrest R.] Univ Florida, Land Use Environm Change Inst, Gainesville, FL USA.
[Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Linard, Catherine] Fonds Natl Rech Sci, B-1050 Brussels, Belgium.
[Linard, Catherine] Univ Libre Brussels, Brussels, Belgium.
RP Gaughan, AE (reprint author), Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
EM aegaughan@gmail.com
RI Stevens, Forrest/B-1673-2013
OI Stevens, Forrest/0000-0002-9328-3753
FU RAPIDD program of the Science and Technology Directorate, Department of
Homeland Security; Bill and Melinda Gates Foundation [49446, 1032350];
Fogarty International Center, National Institutes of Health
FX AJT acknowledges funding support from the RAPIDD program of the Science
and Technology Directorate, Department of Homeland Security, and the
Fogarty International Center, National Institutes of Health, and is also
supported by grants from the Bill and Melinda Gates Foundation (#49446
and #1032350). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 48
TC 36
Z9 39
U1 5
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 FEB 13
PY 2013
VL 8
IS 2
AR e55882
DI 10.1371/journal.pone.0055882
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 104DM
UT WOS:000315970300060
PM 23418469
ER
PT J
AU Zhang, XZ
Daucher, M
Armistead, D
Russell, R
Kottilil, S
AF Zhang, Xiaozhen
Daucher, Marybeth
Armistead, David
Russell, Rodney
Kottilil, Shyam
TI MicroRNA Expression Profiling in HCV-Infected Human Hepatoma Cells
Identifies Potential Anti-Viral Targets Induced by Interferon-alpha
SO PLOS ONE
LA English
DT Article
ID CHRONIC HEPATITIS-C; VIRUS-INFECTION; HEPATOCELLULAR-CARCINOMA; CELLULAR
MICRORNAS; PLUS RIBAVIRIN; LIVER-DISEASES; GENE; MET; MODULATION;
MECHANISM
AB Objective: Increasing evidence suggests that miRNAs have a profound impact on host defense to Hepatitis C virus (HCV) infection and clinical outcome of standard HCV therapy. In this study, we investigated modulation of miRNA expression in Huh7.5 hepatoma cells by HCV infection and in vitro interferon-alpha treatment.
Methods: MiRNA expression profiling was determined using Human miRNA TaqMan (R) Arrays followed by rigorous pairwise statistical analysis. MiRNA inhibitors assessed the functional effects of miRNAs on HCV replication. Computational analysis predicted anti-correlated mRNA targets and their involvement in host cellular pathways. Quantitative RTPCR confirmed the expression of predicted miRNA-mRNA correlated pairs in HCV-infected Huh7.5 cells with and without interferon-alpha.
Results: Seven miRNAs (miR-30b, miR-30c, miR-130a, miR-192, miR-301, miR-324-5p, and miR-565) were down-regulated in HCV-infected Huh7.5 cells (p<0.05) and subsequently up-regulated following interferon-alpha treatment (p<0.01). The miR-30(a-d) cluster and miR-130a/301 and their putative mRNA targets were predicted to be associated with cellular pathways that involve Hepatitis C virus entry, propagation and host response to viral infection.
Conclusions: HCV differentially modulates miRNAs to facilitate entry and early establishment of infection in vitro. Interferon-alpha appears to neutralize the effect of HCV replication on miRNA regulation thus providing a potential mechanism of action in eradicating HCV from hepatocytes.
C1 [Zhang, Xiaozhen; Daucher, Marybeth; Kottilil, Shyam] NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Armistead, David] Life Technol Inc, Gaithersburg, MD USA.
[Russell, Rodney] Mem Univ Newfoundland, Fac Med, Hlth Sci Ctr, St John, NF, Canada.
RP Kottilil, S (reprint author), NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM skottilil@niaid.nih.gov
FU Intramural Research Program of the NIH, [National Institute of Allergy
and Infectious Diseases]
FX The authors declare that they do not have anything to disclose regarding
the funding or conflict of interest with respect to this manuscript. 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 U.S. Government. This research was supported in whole
by the Intramural Research Program of the NIH, [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 35
TC 35
Z9 35
U1 1
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 FEB 13
PY 2013
VL 8
IS 2
AR e55733
DI 10.1371/journal.pone.0055733
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 104DM
UT WOS:000315970300044
PM 23418453
ER
PT J
AU Shao, W
Boltz, VF
Spindler, JE
Kearney, MF
Maldarelli, F
Mellors, JW
Stewart, C
Volfovsky, N
Levitsky, A
Stephens, RM
Coffin, JM
AF Shao, Wei
Boltz, Valerie F.
Spindler, Jonathan E.
Kearney, Mary F.
Maldarelli, Frank
Mellors, John W.
Stewart, Claudia
Volfovsky, Natalia
Levitsky, Alexander
Stephens, Robert M.
Coffin, John M.
TI Analysis of 454 sequencing error rate, error sources, and artifact
recombination for detection of Low-frequency drug resistance mutations
in HIV-1 DNA
SO RETROVIROLOGY
LA English
DT Article
DE 454 pyrosequencing; HIV-1; Error rate; PCR induced recombination
ID REVERSE-TRANSCRIPTASE; MINORITY VARIANTS; VIRAL VARIANTS; PCR; IMPACT;
DIVERSITY; AMPLICONS; ACCURACY; THERAPY; QUALITY
AB Background: 454 sequencing technology is a promising approach for characterizing HIV-1 populations and for identifying low frequency mutations. The utility of 454 technology for determining allele frequencies and linkage associations in HIV infected individuals has not been extensively investigated. We evaluated the performance of 454 sequencing for characterizing HIV populations with defined allele frequencies.
Results: We constructed two HIV-1 RT clones. Clone A was a wild type sequence. Clone B was identical to clone A except it contained 13 introduced drug resistant mutations. The clones were mixed at ratios ranging from 1% to 50% and were amplified by standard PCR conditions and by PCR conditions aimed at reducing PCR-based recombination. The products were sequenced using 454 pyrosequencing. Sequence analysis from standard PCR amplification revealed that 14% of all sequencing reads from a sample with a 50:50 mixture of wild type and mutant DNA were recombinants. The majority of the recombinants were the result of a single crossover event which can happen during PCR when the DNA polymerase terminates synthesis prematurely. The incompletely extended template then competes for primer sites in subsequent rounds of PCR. Although less often, a spectrum of other distinct crossover patterns was also detected. In addition, we observed point mutation errors ranging from 0.01% to 1.0% per base as well as indel (insertion and deletion) errors ranging from 0.02% to nearly 50%. The point errors (single nucleotide substitution errors) were mainly introduced during PCR while indels were the result of pyrosequencing. We then used new PCR conditions designed to reduce PCR-based recombination. Using these new conditions, the frequency of recombination was reduced 27-fold. The new conditions had no effect on point mutation errors. We found that 454 pyrosequencing was capable of identifying minority HIV-1 mutations at frequencies down to 0.1% at some nucleotide positions.
Conclusion: Standard PCR amplification results in a high frequency of PCR-introduced recombination precluding its use for linkage analysis of HIV populations using 454 pyrosequencing. We designed a new PCR protocol that resulted in a much lower recombination frequency and provided a powerful technique for linkage analysis and haplotype determination in HIV-1 populations. Our analyses of 454 sequencing results also demonstrated that at some specific HIV-1 drug resistant sites, mutations can reliably be detected at frequencies down to 0.1%.
C1 [Shao, Wei; Volfovsky, Natalia; Levitsky, Alexander; Stephens, Robert M.] Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD USA.
[Boltz, Valerie F.; Spindler, Jonathan E.; Kearney, Mary F.; Maldarelli, Frank; Coffin, John M.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
[Mellors, John W.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA.
[Stewart, Claudia] Frederick Natl Lab Canc Res, LMT, SAIC Frederick, Frederick, MD USA.
[Coffin, John M.] Tufts Univ, Boston, MA 02111 USA.
RP Shao, W (reprint author), Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, SAIC Frederick, POB B, Frederick, MD USA.
EM shaow@mail.nih.gov
FU National Cancer Institute's intramural Center for Cancer Research;
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; F.M. Kirby Foundation
FX The authors thank Dr. Steve Hughes and Dr. Paul Boyer for reagents, Dr.
Helene Mens, Ann Wiegand for valuable discussion, and Dan Kordella for
assisting making figures. Funding for this research was provided by the
National Cancer Institute's intramural Center for Cancer Research and in
part with federal funds from the National Cancer Institute, National
Institutes of Health, under Contract No. HHSN261200800001E. JMC was a
research professor of the American Cancer Society, with support from the
F.M. Kirby Foundation.
NR 32
TC 49
Z9 49
U1 2
U2 19
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 FEB 13
PY 2013
VL 10
AR 18
DI 10.1186/1742-4690-10-18
PG 16
WC Virology
SC Virology
GA 118WX
UT WOS:000317058500001
PM 23402264
ER
PT J
AU Enose-Akahata, Y
Abrams, A
Massoud, R
Bialuk, I
Johnson, KR
Green, PL
Maloney, EM
Jacobson, S
AF Enose-Akahata, Yoshimi
Abrams, Anna
Massoud, Raya
Bialuk, Izabela
Johnson, Kory R.
Green, Patrick L.
Maloney, Elizabeth M.
Jacobson, Steven
TI Humoral immune response to HTLV-1 basic leucine zipper factor (HBZ) in
HTLV-1-infected individuals
SO RETROVIROLOGY
LA English
DT Article
DE HTLV-1; Antibody; HAM/TSP; ATL; Asymptomatic carriers; Serum; CSF
ID VIRUS TYPE-I; CELL LEUKEMIA-VIRUS; TROPICAL SPASTIC PARAPARESIS; CD8(+)
T-CELLS; NF-KAPPA-B; HUMAN MONOCLONAL-ANTIBODIES; CEREBROSPINAL-FLUID;
PROVIRAL LOAD; INTRATHECAL SYNTHESIS; NEUROLOGIC DISEASE
AB Background: Human T cell lymphotropic virus type 1 (HTLV-1) infection can lead to development of adult T cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a subset of infected subjects. HTLV-1 basic leucine zipper factor (HBZ) gene has a critical role in HTLV-1 infectivity and the development of ATL and HAM/TSP. However, little is known about the immune response against HBZ in HTLV-1-infected individuals. In this study, we examined antibody responses against HBZ in serum/plasma samples from 436 subjects including HTLV-1 seronegative donors, asymptomatic carriers (AC), ATL, and HAM/TSP patients using the luciferase immunoprecipitation system.
Results: Immunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP. However, the frequency of detection of HBZ-specific antibodies in the serum of ATL patients with the chronic subtype was higher than in ATL patients with the lymphomatous subtype. Antibody responses against HBZ were also detected in cerebrospinal fluid of HAM/TSP patients with anti-HBZ in serum. Antibody responses against HBZ did not correlate with proviral load and HBZ mRNA expression in HAM/TSP patients, but the presence of an HBZ-specific response was associated with reduced CD4(+) T cell activation in HAM/TSP patients. Moreover, HBZ-specific antibody inhibited lymphoproliferation in the PBMC of HAM/TSP patients.
Conclusions: This is the first report demonstrating humoral immune response against HBZ associated with HTLV-I infection. Thus, a humoral immune response against HBZ might play a role in HTLV-1 infection.
C1 [Enose-Akahata, Yoshimi; Abrams, Anna; Massoud, Raya; Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Bialuk, Izabela] Med Univ Bialystok, Dept Gen & Expt Pathol, Bialystok, Poland.
[Johnson, Kory R.] NINDS, Bioinformat Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Green, Patrick L.] Ohio State Univ, Ctr Retrovirus Res, Columbus, OH 43210 USA.
[Maloney, Elizabeth M.] NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM JacobsonS@ninds.nih.gov
FU Intramural Research Program of the NINDS, NIH
FX We thank Dr. James Goedert (National Cancer Institute, National
Institutes of Health, Bethesda, MD) for coordinating the specimens and
subjects for this analysis, and Ms. Norma Kim (Research Triangle
Institute, Rockville, MD) for identifying the subjects for this analysis
and arranging for the selection of serum/plasma samples. We thank Dr.
Barrie Hanchard and Ms. Beverley Cranston (the University of the West
Indies, Jamaica) for patient recruitment. We also thank Dr. Peter
Burbelo (National Institute of Dental and Craniofacial Research,
National Institutes of Health, Bethesda, MD) for kindly providing us
with HTLV-1 Gag, Env and Tax/pRen2 plasmids, and Dr. Genoveffa Franchini
(National Cancer Institute, National Institutes of Health, Bethesda, MD)
for HBZ cDNA clone. This research was supported by the Intramural
Research Program of the NINDS, NIH.
NR 58
TC 9
Z9 9
U1 0
U2 3
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 FEB 13
PY 2013
VL 10
AR 19
DI 10.1186/1742-4690-10-19
PG 13
WC Virology
SC Virology
GA 098ZN
UT WOS:000315587900001
PM 23405908
ER
PT J
AU Padayatty, SJ
Levine, M
AF Padayatty, Sebastian J.
Levine, Mark
TI Standard-Dose vs High-Dose Multivitamin Supplements for HIV
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Padayatty, Sebastian J.; Levine, Mark] NIH, Intramural Res Program, Bethesda, MD 20892 USA.
RP Padayatty, SJ (reprint author), NIH, Intramural Res Program, Bldg 10, Bethesda, MD 20892 USA.
EM spadayatty@gmail.com
RI Padayatty, Sebastian/A-8581-2012
OI Padayatty, Sebastian/0000-0001-8758-3170
NR 4
TC 1
Z9 1
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 FEB 13
PY 2013
VL 309
IS 6
BP 545
EP 546
DI 10.1001/jama.2012.216991
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 087PH
UT WOS:000314773700016
PM 23403670
ER
PT J
AU Suren, P
Roth, C
Bresnahan, M
Haugen, M
Hornig, M
Hirtz, D
Lie, KK
Lipkin, WI
Magnus, P
Reichborn-Kjennerud, T
Schjolberg, S
Smith, GD
Oyen, AS
Susser, E
Stoltenberg, C
AF Suren, Pal
Roth, Christine
Bresnahan, Michaeline
Haugen, Margaretha
Hornig, Mady
Hirtz, Deborah
Lie, Kari Kveim
Lipkin, W. Ian
Magnus, Per
Reichborn-Kjennerud, Ted
Schjolberg, Synnve
Smith, George Davey
Oyen, Anne-Siri
Susser, Ezra
Stoltenberg, Camilla
TI Association Between Maternal Use of Folic Acid Supplements and Risk of
Autism Spectrum Disorders in Children
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID NEURAL-TUBE DEFECTS; NORWEGIAN MOTHER; PREGNANT-WOMEN; COHORT;
PREVENTION; VITAMIN; MOBA; PREVALENCE; FOLATE; DELAY
AB Importance Prenatal folic acid supplements reduce the risk of neural tube defects in children, but it has not been determined whether they protect against other neurodevelopmental disorders.
Objective To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder-not otherwise specified [PDD-NOS]) in children.
Design, Setting, and Patients The study sample of 85 176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity.
Main Outcome Measure Specialist-confirmed diagnosis of ASDs.
Results At the end of follow-up, 270 children in the study sample had been diagnosed with ASDs: 114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS. In children whose mothers took folic acid, 0.10% (64/61 042) had autistic disorder, compared with 0.21% (50/24 134) in those unexposed to folic acid. The adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90). No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use.
Conclusions and Relevance Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation. JAMA. 2013;309(6):570-577 www.jama.com
C1 [Suren, Pal; Roth, Christine; Haugen, Margaretha; Lie, Kari Kveim; Magnus, Per; Reichborn-Kjennerud, Ted; Schjolberg, Synnve; Oyen, Anne-Siri; Stoltenberg, Camilla] Norwegian Inst Publ Hlth, N-0403 Oslo, Norway.
[Suren, Pal] UCL Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England.
[Roth, Christine; Bresnahan, Michaeline; Hornig, Mady; Lipkin, W. Ian; Susser, Ezra] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Bresnahan, Michaeline; Susser, Ezra] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Hirtz, Deborah] NINDS, Bethesda, MD 20892 USA.
[Reichborn-Kjennerud, Ted] Univ Oslo, Inst Psychiat, Oslo, Norway.
[Smith, George Davey] Univ Bristol, MRC Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England.
[Oyen, Anne-Siri] Lovisenberg Hosp, Nic Waals Inst, Oslo, Norway.
[Stoltenberg, Camilla] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
RP Suren, P (reprint author), Norwegian Inst Publ Hlth, POB 4404, N-0403 Oslo, Norway.
EM pal.suren@fhi.no
OI Monsalve, Beatriz Elena/0000-0002-5994-866X; Davey Smith,
George/0000-0002-1407-8314
FU Norwegian Ministry of Health and Care Services; Norwegian Ministry of
Education and Research; Research Council of Norway/FUGE [151918];
National Institute of Neurological Disorders and Stroke (NINDS)
[NS47537]; National Institute of Environmental Health Sciences (NIEHS)
[NO-ES-75558]; NINDS [NS47537]; Research Council of Norway [185476,
190694]
FX The Norwegian Mother and Child Cohort is supported by the Norwegian
Ministry of Health and Care Services, the Norwegian Ministry of
Education and Research, the Research Council of Norway/FUGE (grant
151918), the National Institute of Neurological Disorders and Stroke
(NINDS) (grant NS47537 [Dr Lipkin]), and the National Institute of
Environmental Health Sciences (NIEHS) (contract NO-ES-75558). The Autism
Birth Cohort study is funded by the NINDS (grant NS47537 [Dr Lipkin]).
Dr Suren's salary is funded by the Research Council of Norway (grants
185476 and 190694).
NR 25
TC 124
Z9 135
U1 10
U2 75
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 FEB 13
PY 2013
VL 309
IS 6
BP 570
EP 577
DI 10.1001/jama.2012.155925
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 087PH
UT WOS:000314773700029
PM 23403681
ER
PT J
AU Meinhardt, MW
Hansson, AC
Perreau-Lenz, S
Bauder-Wenz, C
Stahlin, O
Heilig, M
Harper, C
Drescher, KU
Spanagel, R
Sommer, WH
AF Meinhardt, Marcus W.
Hansson, Anita C.
Perreau-Lenz, Stephanie
Bauder-Wenz, Christina
Staehlin, Oliver
Heilig, Markus
Harper, Clive
Drescher, Karla U.
Spanagel, Rainer
Sommer, Wolfgang H.
TI Rescue of Infralimbic mGluR(2) Deficit Restores Control Over
Drug-Seeking Behavior in Alcohol Dependence
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CORTICOTROPIN-RELEASING-FACTOR; PREFRONTAL CORTEX; GLUTAMATE
TRANSMISSION; INDUCED REINSTATEMENT; ETHANOL EXPOSURE; COCAINE-SEEKING;
GENE-EXPRESSION; NEGATIVE AFFECT; RATS; WITHDRAWAL
AB A key deficit in alcohol dependence is disrupted prefrontal function leading to excessive alcohol seeking, but the molecular events underlying the emergence of addictive responses remain unknown. Here we show by convergent transcriptome analysis that the pyramidal neurons of the infralimbic cortex are particularly vulnerable for the long-term effects of chronic intermittent ethanol intoxication. These neurons exhibit a pronounced deficit in metabotropic glutamate receptor subtype 2 (mGluR(2)). Also, alcohol-dependent rats do not respond to mGluR(2/3) agonist treatment with reducing extracellular glutamate levels in the nucleus accumbens. Together these data imply a loss of autoreceptor feedback control. Alcohol-dependent rats show escalation of ethanol seeking, which was abolished by restoring mGluR(2) expression in the infralimbic cortex via viral-mediated gene transfer. Human anterior cingulate cortex from alcoholic patients shows a significant reduction in mGluR(2) transcripts compared to control subjects, suggesting that mGluR(2) loss in the rodent and human corticoaccumbal neurocircuitry may be a major consequence of alcohol dependence and a key pathophysiological mechanism mediating increased propensity to relapse. Normalization of mGluR(2) function within this brain circuit may be of therapeutic value.
C1 [Meinhardt, Marcus W.; Hansson, Anita C.; Perreau-Lenz, Stephanie; Bauder-Wenz, Christina; Staehlin, Oliver; Spanagel, Rainer; Sommer, Wolfgang H.] Heidelberg Univ, Med Fac Mannheim, Inst Psychopharmacol, Cent Inst Mental Hlth, D-68159 Mannheim, Germany.
[Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Harper, Clive] Univ Sydney, New S Wales Tissue Resource Ctr, Sydney, NSW 2006, Australia.
[Drescher, Karla U.] Abbott Neurosci Res, D-67061 Ludwigshafen, Germany.
RP Sommer, WH (reprint author), Cent Inst Mental Hlth, Sq J5, D-68159 Mannheim, Germany.
EM wolfgang.sommer@zi-mannheim.de
RI Perreau-Lenz, Stephanie/D-2309-2014
OI Perreau-Lenz, Stephanie/0000-0001-9529-6403
FU Bundesministerium fur Bildung und Forschung within the frameworks of
NGFN Plus [FKZ 01GS08151, 01GS08152, 01GS08155]; ERA-Net TRANSALC [FKZ
01EW1112]; European Commission FP-6 Integrated Project IMAGEN
[PL037286]; Deutsche Forschungsgemeinschaft [SFB636, HA 6102/1-1, SP
383/5-1]; Intramural Research Program of the NIAAA
FX This work was supported by the Bundesministerium fur Bildung und
Forschung within the frameworks of NGFN Plus (FKZ 01GS08151, 01GS08152,
and 01GS08155; see www.ngfn-alkohol.de, Spanagel et al., 2010) and
ERA-Net TRANSALC (FKZ 01EW1112), the European Commission FP-6 Integrated
Project IMAGEN (PL037286), the Deutsche Forschungsgemeinschaft (Center
Grant SFB636; project Grant HA 6102/1-1 to A. C. H.; Reinhart-Koselleck
Award SP 383/5-1 to R. S.), and the Intramural Research Program of the
NIAAA (M. H.). We thank Elisabeth Robel and Fernando Leonardi-Essmann
for assistance in laboratory experiments.
NR 64
TC 46
Z9 47
U1 0
U2 5
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 FEB 13
PY 2013
VL 33
IS 7
BP 2794
EP 2806
DI 10.1523/JNEUROSCI.4062-12.2013
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 089CQ
UT WOS:000314887200007
PM 23407939
ER
PT J
AU Alexander-Bloch, A
Raznahan, A
Bullmore, ET
Giedd, J
AF Alexander-Bloch, Aaron
Raznahan, Armin
Bullmore, Ed T
Giedd, Jay
TI The Convergence of Maturational Change and Structural Covariance in
Human Cortical Networks
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID STATE FUNCTIONAL CONNECTIVITY; GRAPH-THEORETICAL ANALYSIS; DEFAULT MODE
NETWORK; HUMAN BRAIN; CEREBRAL-CORTEX; MRI; SCHIZOPHRENIA; THICKNESS;
ORGANIZATION; ARCHITECTURE
AB Large-scale covariance of cortical thickness or volume in distributed brain regions has been consistently reported by human neuroimaging studies. The mechanism of this population covariance of regional cortical anatomy has been hypothetically related to synchronized maturational changes in anatomically connected neuronal populations. Brain regions that grow together, i.e., increase or decrease in volume at the same rate over the course of years in the same individual, are thus expected to demonstrate strong structural covariance or anatomical connectivity across individuals. To test this prediction, we used a structural MRI dataset on healthy young people (N = 108; aged 9-22 years at enrollment), comprising 3-6 longitudinal scans on each participant over 6-12 years of follow-up. At each of 360 regional nodes, and for each participant, we estimated the following: (1) the cortical thickness in the median scan and (2) the linear rate of change in cortical thickness over years of serial scanning. We constructed structural and maturational association matrices and networks from these measurements. Both structural and maturational networks shared similar global and nodal topological properties, as well as mesoscopic features including a modular community structure, a relatively small number of highly connected hub regions, and a bias toward short distance connections. Using resting-state functional magnetic resonance imaging data on a subset of the sample (N = 32), we also demonstrated that functional connectivity and network organization was somewhat predictable by structural/maturational networks but demonstrated a stronger bias toward short distance connections and greater topological segregation. Brain structural covariance networks are likely to reflect synchronized developmental change in distributed cortical regions.
C1 [Alexander-Bloch, Aaron; Bullmore, Ed T] Univ Cambridge, Dept Psychiat, Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England.
[Alexander-Bloch, Aaron; Raznahan, Armin; Giedd, Jay] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
[Alexander-Bloch, Aaron] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Bullmore, Ed T] Addenbrookes Hosp, GlaxoSmithKline, Clin Unit Cambridge, Cambridge CB2 2GG, England.
[Bullmore, Ed T] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge CB21 5EF, England.
RP Alexander-Bloch, A (reprint author), NIMH, Child Psychiat Branch, 10 Ctr Dr,MSC 1367,Bldg 10,Room 4C110, Bethesda, MD 20892 USA.
EM aalexanderbloch@gmail.com; jgiedd@mail.nih.gov
RI Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; Bullmore,
Edward/C-1706-2012;
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978;
Bullmore, Edward/0000-0002-8955-8283; Alexander-Bloch,
Aaron/0000-0001-6554-1893
FU National Institute of Mental Health, National Institutes of Health
Intramural Research Program; National Institutes of
Health-Oxford-Cambridge Scholarship Program; Medical Research Council
(UK); Wellcome Trust
FX This study was funded through the National Institute of Mental Health,
the National Institutes of Health Intramural Research Program, and the
National Institutes of Health-Oxford-Cambridge Scholarship Program (A.
A. B.). The Behavioural and Clinical Neuroscience Institute is supported
by the Medical Research Council (UK) and the Wellcome Trust. We wish to
thank Francois Lalonde and Liv Clasen for help with data collection and
analysis, Budhachandra Khundrakpam for assistance with the AAL atlas,
and also the participants who took part in this study.
NR 72
TC 85
Z9 85
U1 1
U2 25
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD FEB 13
PY 2013
VL 33
IS 7
BP 2889
EP +
DI 10.1523/JNEUROSCI.3554-12.2013
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 089CQ
UT WOS:000314887200015
PM 23407947
ER
PT J
AU Lehmann, ML
Brachman, RA
Martinowich, K
Schloesser, RJ
Herkenham, M
AF Lehmann, Michael L.
Brachman, Rebecca A.
Martinowich, Keri
Schloesser, Robert J.
Herkenham, Miles
TI Glucocorticoids Orchestrate Divergent Effects on Mood through Adult
Neurogenesis
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID PITUITARY-ADRENOCORTICAL AXIS; RECEPTOR MESSENGER-RNA;
CORTICOTROPIN-RELEASING HORMONE; HIPPOCAMPAL NEUROGENESIS; VOLUNTARY
EXERCISE; DENTATE GYRUS; CHRONIC STRESS; VENTRAL HIPPOCAMPUS; MAJOR
DEPRESSION; RAT-BRAIN
AB Both social defeat stress and environmental enrichment stimulate adrenal glucocorticoid secretion, but they have opposing effects on hippocampal neurogenesis and mood. Hypothalamic-pituitary-adrenal axis dysregulation and decreased neurogenesis are consequences of social defeat. These outcomes are correlated with depressive states, but a causal role in the etiology of depression remains elusive. The antidepressant actions of environmental enrichment are neurogenesis-dependent, but the contribution of enrichment-elevated glucocorticoids is unexplored. Importantly, for both social defeat and environmental enrichment, how glucocorticoids interact with neurogenesis to alter mood is unknown. Here, we investigate causal roles of glucocorticoids and neurogenesis in induction of depressive-like behavior and its amelioration by environmental enrichment in mice. By blocking neurogenesis and surgically clamping adrenal hormone secretions, we showed that neurogenesis, via hypothalamic-pituitary-adrenal axis interactions, is directly involved in precipitating the depressive phenotype after social defeat. Mice adrenalectomized before social defeat showed enhanced behavioral resiliency and increased survival of adult-born hippocampal neurons compared with sham-operated defeated mice. However, mice lacking hippocampal neurogenesis did not show protective effects of adrenalectomy. Moreover, glucocorticoids secreted during environmental enrichment promoted neurogenesis and were required for restoration of normal behavior after social defeat. The data demonstrate that glucocorticoid-dependent declines in neurogenesis drive changes in mood after social defeat and that glucocorticoids secreted during enrichment promote neurogenesis and restore normal behavior after defeat. These data provide new evidence for direct involvement of neurogenesis in the etiology of depression, suggesting that treatments promoting neurogenesis can enhance stress resilience.
C1 [Lehmann, Michael L.; Brachman, Rebecca A.; Herkenham, Miles] NIMH, Funct Neuroanat Sect, NIH, Bethesda, MD 20892 USA.
[Martinowich, Keri; Schloesser, Robert J.] NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA.
RP Lehmann, ML (reprint author), NIMH, Funct Neuroanat Sect, NIH, Bethesda, MD 20892 USA.
EM Michael.lehmann@nih.gov
RI Martinowich, Keri/F-9841-2012;
OI Brachman, Rebecca/0000-0002-1221-0414; Martinowich,
Keri/0000-0002-5237-0789; Herkenham, Miles/0000-0003-2228-4238; Lehmann,
Michael/0000-0003-4476-8268
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health. We
thank Jason Snyder for helpful comments on the manuscript.
NR 72
TC 50
Z9 53
U1 0
U2 40
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 FEB 13
PY 2013
VL 33
IS 7
BP 2961
EP 2972
DI 10.1523/JNEUROSCI.3878-12.2013
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 089CQ
UT WOS:000314887200022
PM 23407954
ER
PT J
AU Koizumi, H
Koshiya, N
Chia, JX
Cao, F
Nugent, J
Zhang, RL
Smith, JC
AF Koizumi, Hidehiko
Koshiya, Naohiro
Chia, Justine X.
Cao, Fang
Nugent, Joseph
Zhang, Ruli
Smith, Jeffrey C.
TI Structural-Functional Properties of Identified Excitatory and Inhibitory
Interneurons within Pre-Botzinger Complex Respiratory Microcircuits
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID MAMMALIAN BRAIN-STEM; RAT SPINAL-CORD; KNOCK-IN MOUSE; RHYTHM
GENERATION; PREBOTZINGER COMPLEX; PACEMAKER NEURONS;
MEMBRANE-PROPERTIES; PATTERN GENERATION; DENDRITIC SPINES; NETWORK
AB We comparatively analyzed cellular and circuit properties of identified rhythmic excitatory and inhibitory interneurons within respiratory microcircuits of the neonatal rodent pre-Botzinger complex (pre-BotC), the structure generating inspiratory rhythm in the brainstem. We combined high-resolution structural-functional imaging, molecular assays for neurotransmitter phenotype identification in conjunction with electrophysiological property phenotyping, and morphological reconstruction of interneurons in neonatal rat and mouse slices in vitro. This approach revealed previously undifferentiated structural-functional features that distinguish excitatory and inhibitory interneuronal populations. We identified distinct subpopulations of pre-BotC glutamatergic, glycinergic, GABAergic, and glycine-GABA coexpressing interneurons. Most commissural pre-BotC inspiratory interneurons were glutamatergic, with a substantial subset exhibiting intrinsic oscillatory bursting properties. Commissural excitatory interneurons projected with nearly planar trajectories to the contralateral pre-BotC, many also with axon collaterals to areas containing inspiratory hypoglossal (XII) premotoneurons and motoneurons. Inhibitory neurons as characterized in the present study did not exhibit intrinsic oscillatory bursting properties, but were electrophysiologically distinguished by more pronounced spike frequency adaptation properties. Axons of many inhibitory neurons projected ipsilaterally also to regions containing inspiratory XII premotoneurons and motoneurons, whereas a minority of inhibitory neurons had commissural axonal projections. Dendrites of both excitatory and inhibitory interneurons were arborized asymmetrically, primarily in the coronal plane. The dendritic fields of inhibitory neurons were more spatially compact than those of excitatory interneurons. Our results are consistent with the concepts of a compartmental circuit organization, a bilaterally coupled excitatory rhythmogenic kernel, and a role of pre-BotC inhibitory neurons in shaping inspiratory pattern as well as coordinating inspiratory and expiratory activity.
C1 [Koizumi, Hidehiko; Koshiya, Naohiro; Chia, Justine X.; Cao, Fang; Nugent, Joseph; Zhang, Ruli; Smith, Jeffrey C.] Natl Inst Neurol Disorders & Stroke, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Smith, JC (reprint author), NINDS, NIH, 49 Convent Dr,Room 2A10, Bethesda, MD 20892 USA.
EM smithj2@helix.nih.gov
OI Nugent, Joseph/0000-0002-6863-4523
FU NIH, National Institute of Neurological Disorders and Stroke
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Neurological Disorders and Stroke. We thank
Professor Yuchio Yanagawa of Gunma University, Japan for generously
providing GAD67-GFP knock-in mice.
NR 54
TC 29
Z9 29
U1 0
U2 13
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 FEB 13
PY 2013
VL 33
IS 7
BP 2994
EP 3009
DI 10.1523/JNEUROSCI.4427-12.2013
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA 089CQ
UT WOS:000314887200025
PM 23407957
ER
PT J
AU De Pisapia, N
Bornstein, MH
Rigo, P
Esposito, G
De Falco, S
Venuti, P
AF De Pisapia, Nicola
Bornstein, Marc H.
Rigo, Paola
Esposito, Gianluca
De Falco, Simona
Venuti, Paola
TI Sex differences in directional brain responses to infant hunger cries
SO NEUROREPORT
LA English
DT Article
DE brain; default-mode network; infant cry; medial prefrontal cortex; mind
wandering; parenting; posterior cingulate cortex
ID DEFAULT; NETWORKS; TASK; FMRI
AB Infant cries are a critical survival mechanism that draw the attention of adult caregivers, who can then satisfy the basic needs of otherwise helpless infants. Here, we used functional neuroimaging to determine the effects of infant hunger cries on the brain activity of adults who were in a cognitively nondemanding mental state of awake rest. We found that the brains of men and women, independent of parental status (parent or nonparent), reacted differently to infant cries. Specifically, the dorsal medial prefrontal and posterior cingulate areas, known to be involved in mind wandering (the stream of thought typical of awake rest), remained active in men during exposure to infant cries, whereas in women, activity in these regions decreased. These results show sex-dependent modulation of brain responses to infant requests to be fed, and specifically, they indicate that women interrupt mind wandering when exposed to the sounds of infant hunger cries, whereas men carry on without interruption. NeuroReport 24:142-146 (c) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [De Pisapia, Nicola; Rigo, Paola; De Falco, Simona; Venuti, Paola] Univ Trent, Dept Cognit Sci & Educ, Trento, Italy.
[Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Publ Hlth Serv, Rockville, MD USA.
[Esposito, Gianluca] RIKEN Brain Sci Inst, Kuroda Res Unit Affiliat Social Behav, Saitama, Japan.
RP De Pisapia, N (reprint author), Univ Trent, DiSCoF Dept Cognit Sci, I-38068 Rovereto, Italy.
EM nicola.depisapia@unitn.it
RI Esposito, Gianluca/B-1374-2012; Esposito, Gianluca/K-9353-2013;
OI Esposito, Gianluca/0000-0002-9442-0254; Esposito,
Gianluca/0000-0002-9442-0254; De Pisapia, Nicola/0000-0002-1089-8841
FU Intramural Research Program of the NIH, NICHD
FX This research was supported by the Intramural Research Program of the
NIH, NICHD.
NR 25
TC 23
Z9 23
U1 2
U2 32
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0959-4965
J9 NEUROREPORT
JI Neuroreport
PD FEB 13
PY 2013
VL 24
IS 3
BP 142
EP 146
DI 10.1097/WNR.0b013e32835df4fa
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 082CI
UT WOS:000314368900008
PM 23282991
ER
PT J
AU Hickman, HD
Reynoso, GV
Ngudiankama, BF
Rubin, EJ
Magadan, JG
Cush, SS
Gibbs, J
Molon, B
Bronte, V
Bennink, JR
Yewdell, JW
AF Hickman, Heather D.
Reynoso, Glennys V.
Ngudiankama, Barbara F.
Rubin, Erica J.
Magadan, Javier G.
Cush, Stephanie S.
Gibbs, James
Molon, Barbara
Bronte, Vincenzo
Bennink, Jack R.
Yewdell, Jonathan W.
TI Anatomically Restricted Synergistic Antiviral Activities of Innate and
Adaptive Immune Cells in the Skin
SO CELL HOST & MICROBE
LA English
DT Article
ID CD8 T-CELLS; SUBCAPSULAR SINUS MACROPHAGES; VACCINIA VIRUS-INFECTION;
LYMPH-NODES; IN-VIVO; RESPONSES; MICE; REPLICATION; EXPRESSION;
PROTECTION
AB Despite extensive ex vivo investigation, the spatiotemporal organization of immune cells interacting with virus-infected cells in tissues remains uncertain. To address this, we used intravital multiphoton microscopy to visualize immune cell interactions with virus-infected cells following epicutaneous vaccinia virus (VV) infection of mice. VV infects keratinocytes in epidermal foci and numerous migratory dermal inflammatory monocytes that outlie the foci. We observed Ly6G(+) innate immune cells infiltrating and controlling foci, while CD8(+) T cells remained on the periphery killing infected monocytes. Most antigen-specific CD8(+) T cells in the skin did not interact with virus-infected cells. Blocking the generation of reactive nitrogen species relocated CD8(+) T cells into foci, modestly reducing viral titers. Depletion of Ly6G(+) and CD8(+) cells dramatically increased viral titers, consistent with their synergistic but spatially segregated viral clearance activities. These findings highlight previously unappreciated differences in the anatomic specialization of antiviral immune cell subsets.
C1 [Hickman, Heather D.; Reynoso, Glennys V.; Ngudiankama, Barbara F.; Rubin, Erica J.; Magadan, Javier G.; Cush, Stephanie S.; Gibbs, James; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Molon, Barbara] IRCCS, Ist Oncol Veneto, I-35128 Padua, Italy.
[Bronte, Vincenzo] Verona Univ Hosp, Dept Pathol, Immunol Sect, I-37134 Verona, Italy.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM jyewdell@mail.nih.gov
RI Bronte, Vincenzo/K-7902-2016
OI Bronte, Vincenzo/0000-0002-3741-5141
FU National Institute of Allergy and Infectious Diseases Division of
Intramural Research
FX We thank the Comparative Medicine Branch and staff of the NIH Building
33 vivarium for excellence in animal husbandry. This work was generously
supported by the National Institute of Allergy and Infectious Diseases
Division of Intramural Research.
NR 38
TC 19
Z9 19
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 FEB 13
PY 2013
VL 13
IS 2
BP 155
EP 168
DI 10.1016/j.chom.2013.01.004
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AA1IQ
UT WOS:000330850200007
PM 23414756
ER
PT J
AU Chamanian, M
Purzycka, KJ
Wille, PT
Ha, JS
McDonald, D
Gao, Y
Le Grice, SFJ
Arts, EJ
AF Chamanian, Mastooreh
Purzycka, Katarzyna J.
Wille, Paul T.
Ha, Janice S.
McDonald, David
Gao, Yong
Le Grice, Stuart F. J.
Arts, Eric J.
TI A cis-Acting Element in Retroviral Genomic RNA Links Gag-Pol Ribosomal
Frameshifting to Selective Viral RNA Encapsidation
SO CELL HOST & MICROBE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1 LEADER RNA; SECONDARY STRUCTURE;
INFECTIOUS TITER; PROTEIN; DIMERIZATION; IDENTIFICATION; SITE;
RECOMBINATION; RECOGNITION
AB During retroviral RNA encapsidation, two full-length genomic (g) RNAs are selectively incorporated into assembling virions. Packaging involves a cis-acting packaging element (Psi) within the 5' untranslated region of unspliced HIV-1 RNA genome. However, the mechanism(s) that selects and limits gRNAs for packaging remains uncertain. Using a dual complementation system involving bipartite HIV-1 gRNA, we observed that gRNA packaging is additionally dependent on a cis-acting RNA element, the genomic RNA packaging enhancer (GRPE), found within the gag p1-p6 domain and overlapping the Gag-Pol ribosomal frameshift signal. Deleting or disrupting the two conserved GRPE stem loops diminished gRNA packaging and infectivity >50-fold, while deleting gag sequences between Psi and GRPE had no effect. Downregulating the translation termination factor eRF1 produces defective virus particles containing 20 times more gRNA. Thus, only the HIV-1 RNAs employed for Gag-Pol translation may be specifically selected for encapsidation, possibly explaining the limitation of two gRNAs per virion.
C1 [Chamanian, Mastooreh; McDonald, David; Gao, Yong; Arts, Eric J.] Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA.
[Purzycka, Katarzyna J.; Le Grice, Stuart F. J.] NCI, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Wille, Paul T.; Ha, Janice S.; Gao, Yong; Arts, Eric J.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA.
RP Arts, EJ (reprint author), Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA.
EM eja3@case.edu
FU Center for Cancer Research, NCI, NIH; NIAID, NIH [R01 AI49170, AI084816]
FX We want to thank Mianda Wu for helping with real-time PCR. S.F.J.L. and
K.J.P. were supported by the Intramural Research Program of the Center
for Cancer Research, NCI, NIH. This study and all remaining authors were
funded by NIAID, NIH R01 AI49170 and AI084816. Core support was provided
by the CWRU/UH CFAR (AI36219).
NR 42
TC 19
Z9 19
U1 1
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD FEB 13
PY 2013
VL 13
IS 2
BP 181
EP 192
DI 10.1016/j.chom.2013.01.007
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AA1IQ
UT WOS:000330850200009
PM 23414758
ER
PT J
AU Chowell, G
Viboud, C
AF Chowell, Gerardo
Viboud, Cecile
TI A practical method to target individuals for outbreak detection and
control
SO BMC MEDICINE
LA English
DT Editorial Material
DE contact network; hotspot; dynamic network; contact pattern; wireless
sensing devices; collocation ranking; class schedule; high school;
influenza; disease transmission
ID INFECTIOUS-DISEASE; SOCIAL NETWORKS; INFLUENZA; TRANSMISSION; CLOSURE
AB Identification of individuals or subpopulations that contribute the most to disease transmission is key to target surveillance and control efforts. In a recent study in BMC Medicine, Smieszek and Salathe introduced a novel method based on readily available information about spatial proximity in high schools, to help identify individuals at higher risk of infection and those more likely to be infected early in the outbreak. By combining simulation models for influenza transmission with high-resolution data on school contact patterns, the authors showed that their proximity method compares favorably to more sophisticated methods using detailed contact tracing information. The proximity method is simple and promising, but further research is warranted to confront this method against real influenza outbreak data, and to assess the generalizability of the approach to other important transmission units, such as work, households, and transportation systems. See related research article here http://www.biomedcentral.com/1741-7015/11/35
C1 [Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Math & Computat Modeling Sci Ctr, Tempe, AZ 85069 USA.
[Chowell, Gerardo; Viboud, Cecile] NIH, Fogarty Int Ctr, Div Int Epidemiol & Populat Studies, Bethesda, MD 20892 USA.
RP Chowell, G (reprint author), Arizona State Univ, Sch Human Evolut & Social Change, Math & Computat Modeling Sci Ctr, Tempe, AZ 85069 USA.
EM gchowell@asu.edu
RI Chowell, Gerardo/F-5038-2012; Chiang, Vincent, Ming-Hsien/D-4312-2016
OI Chowell, Gerardo/0000-0003-2194-2251; Chiang, Vincent,
Ming-Hsien/0000-0002-2029-7863
NR 18
TC 4
Z9 4
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD FEB 12
PY 2013
VL 11
AR 36
DI 10.1186/1741-7015-11-36
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 137IW
UT WOS:000318430200002
PM 23402649
ER
PT J
AU Spencer, KL
Malinowski, J
Carty, CL
Franceschini, N
Fernandez-Rhodes, L
Young, A
Cheng, I
Ritchie, MD
Haiman, CA
Wilkens, L
ChunyuanWu
Matise, TC
Carlson, CS
Brennan, K
Park, A
Rajkovic, A
Hindorff, LA
Buyske, S
Crawford, DC
AF Spencer, Kylee L.
Malinowski, Jennifer
Carty, Cara L.
Franceschini, Nora
Fernandez-Rhodes, Lindsay
Young, Alicia
Cheng, Iona
Ritchie, Marylyn D.
Haiman, Christopher A.
Wilkens, Lynne
ChunyuanWu
Matise, Tara C.
Carlson, Christopher S.
Brennan, Kathleen
Park, Amy
Rajkovic, Aleksandar
Hindorff, Lucia A.
Buyske, Steven
Crawford, Dana C.
TI Genetic Variation and Reproductive Timing: African American Women from
the Population Architecture Using Genomics and Epidemiology (PAGE) Study
SO PLOS ONE
LA English
DT Article
ID BODY-MASS INDEX; CARDIOVASCULAR-DISEASE RISK; LIFE-STYLE FACTORS;
NATURAL MENOPAUSE; WIDE ASSOCIATION; BREAST-CANCER; CAUCASIAN FEMALES;
BREAKTHROUGH GENERATIONS; FUNCTIONAL-ANALYSIS; ENDOMETRIAL CANCER
AB Age at menarche (AM) and age at natural menopause (ANM) define the boundaries of the reproductive lifespan in women. Their timing is associated with various diseases, including cancer and cardiovascular disease. Genome-wide association studies have identified several genetic variants associated with either AM or ANM in populations of largely European or Asian descent women. The extent to which these associations generalize to diverse populations remains unknown. Therefore, we sought to replicate previously reported AM and ANM findings and to identify novel AM and ANM variants using the Metabochip (n = 161,098 SNPs) in 4,159 and 1,860 African American women, respectively, in the Women's Health Initiative (WHI) and Atherosclerosis Risk in Communities (ARIC) studies, as part of the Population Architecture using Genomics and Epidemiology (PAGE) Study. We replicated or generalized one previously identified variant for AM, rs1361108/CENPW, and two variants for ANM, rs897798/BRSK1 and rs769450/APOE, to our African American cohort. Overall, generalization of the majority of previously-identified variants for AM and ANM, including LIN28B and MCM8, was not observed in this African American sample. We identified three novel loci associated with ANM that reached significance after multiple testing correction (LDLR rs189596789, p = 5 x 10(-08); KCNQ1 rs79972789, p = 1.9 x 10(-07); COL4A3BP rs181686584, p = 2.9 x 10(-07)). Our most significant AM association was upstream of RSF1, a gene implicated in ovarian and breast cancers (rs11604207, p = 1.6 x 10(-06)). While most associations were identified in either AM or ANM, we did identify genes suggestively associated with both: PHACTR1 and ARHGAP42. The lack of generalization coupled with the potentially novel associations identified here emphasize the need for additional genetic discovery efforts for AM and ANM in diverse populations.
C1 [Malinowski, Jennifer; Ritchie, Marylyn D.; Crawford, Dana C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Ctr Human Genet Res, Nashville, TN 37232 USA.
[Matise, Tara C.; Buyske, Steven] Rutgers State Univ, Dept Genet, Piscataway, NJ USA.
[Buyske, Steven] Rutgers State Univ, Dept Stat, Piscataway, NJ USA.
[Franceschini, Nora; Fernandez-Rhodes, Lindsay] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Carty, Cara L.; Young, Alicia; ChunyuanWu; Carlson, Christopher S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Cheng, Iona; Wilkens, Lynne] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Brennan, Kathleen] Univ Calif Los Angeles, Dept Obstet & Gynecol, Los Angeles, CA 90024 USA.
[Park, Amy] Georgetown Univ, Sch Med, Dept Obstet & Gynecol, Washington, DC 20007 USA.
[Rajkovic, Aleksandar] Univ Pittsburgh, Magee Womens Res Inst, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Hindorff, Lucia A.] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA.
[Spencer, Kylee L.] Heidelberg Univ, Dept Biol & Environm Sci, Tiffin, OH USA.
[Ritchie, Marylyn D.] Penn State Univ, University Pk, MD USA.
RP Crawford, DC (reprint author), Vanderbilt Univ, Dept Mol Physiol & Biophys, Ctr Human Genet Res, Nashville, TN 37232 USA.
EM dana.c.crawford@vanderbilt.edu
OI Buyske, Steven/0000-0001-8539-5416
FU National Human Genome Research Institute (NHGRI); Causal Variants Across
the Life Course, known as CALiCo [U01HG004803]; Epidemiologic
Architecture for Genes Linked to Environment, known as EAGLE
[U01HG004798]; Multiethnic Cohort, known as MEC [U01HG004802]; Women's
Health Initiative, known as WHI [U01HG004790]; Coordinating Center
[U01HG004801]; NHLBI [N01-HC-55015, N01-HC-55016, N01-HC-55018,
N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022]; National Cancer
Institute [R37CA54281, R01 CA63, P01CA33619, U01CA136792, U01CA98758];
National Heart, Lung, and Blood Institute (NHLBI) (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]; National Institutes of Mental Health
FX The Population Architecture Using Genomics and Epidemiology (PAGE)
program is funded by the National Human Genome Research Institute
(NHGRI), supported by U01HG004803 (Causal Variants Across the Life
Course, known as CALiCo), U01HG004798 (Epidemiologic Architecture for
Genes Linked to Environment, known as EAGLE), U01HG004802 (the
Multiethnic Cohort, known as MEC), U01HG004790 (Women's Health
Initiative, known as WHI), and U01HG004801 (Coordinating Center). The
Atherosclerosis Risk in Communities (ARIC) Study is carried out as a
collaborative study supported by NHLBI contracts N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022. The Multiethnic Cohort (MEC) study is funded through the
National Cancer Institute (R37CA54281, R01 CA63, P01CA33619,
U01CA136792, and U01CA98758). The Women's Health Initiative (WHI)
program is funded by the National Heart, Lung, and Blood Institute
(NHLBI) (NIH) and by 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
National Institutes of Mental Health also contributes to the support for
the Coordinating Center. NHGRI collaborators (LAH) assisted in the study
design, analysis, and preparation of the manuscript.
NR 95
TC 14
Z9 14
U1 1
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 12
PY 2013
VL 8
IS 2
AR e55258
DI 10.1371/journal.pone.0055258
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 104BU
UT WOS:000315965100014
PM 23424626
ER
PT J
AU Mannisto, T
Mendola, P
Vaarasmaki, M
Jarvelin, MR
Hartikainen, AL
Pouta, A
Suvanto, E
AF Maennistoe, Tuija
Mendola, Pauline
Vaarasmaki, Marja
Jarvelin, Marjo-Riitta
Hartikainen, Anna-Liisa
Pouta, Anneli
Suvanto, Eila
TI Elevated Blood Pressure in Pregnancy and Subsequent Chronic Disease Risk
SO CIRCULATION
LA English
DT Article
DE epidemiology; hypertension; myocardial infarction; pregnancy;
prevention; stroke
ID HOSPITAL DISCHARGE REGISTER; ISCHEMIC-HEART-DISEASE; HYPERTENSIVE
PREGNANCY; CARDIOVASCULAR-DISEASE; RETROSPECTIVE COHORT; UNITED-STATES;
LATER LIFE; PREECLAMPSIA; COMPLICATIONS; MORTALITY
AB Background-Preeclampsia, a new-onset hypertensive disorder of pregnancy, is associated with lifetime cardiovascular disease risk, but less is known about risk after other pregnancy-related hypertension.
Methods and Results-The Northern Finland Birth Cohort 1966 included all expected births from 1 year (N=12 055 women). Blood pressure measurements and other prospective data were determined from prenatal care records and questionnaires for 10 314 women. Subsequent diagnoses were ascertained from Finnish registries (average follow-up, 39.4 years). Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) estimate risks in hypertensive women compared with normotensive women. Hypertension during pregnancy was associated with increased risk of subsequent cardiovascular disease and arterial hypertension. Women with chronic hypertension and superimposed preeclampsia/eclampsia had high risk for future diseases. Gestational hypertension was associated with increased risk of ischemic heart disease (HR, 1.44 [95% CI, 1.24-1.68]), myocardial infarcts (HR, 1.75 [95% CI, 1.40-2.19]), myocardial infarct death (HR, 3.00 [95% CI, 1.98-4.55]), heart failure (HR, 1.78 [95% CI, 1.43-2.21]), ischemic stroke (HR, 1.59 [95% CI, 1.24-2.04]), kidney disease (HR, 1.91 [95% CI, 1.18-3.09]), and diabetes mellitus (HR, 1.52 [95% CI, 1.21-1.89]). Isolated systolic hypertension was associated with increased risk of myocardial infarct death (HR, 2.15 [95% CI, 1.35-3.41]), heart failure (HR, 1.43 [95% CI, 1.13-1.82]), and diabetes mellitus (HR, 1.42 [95% CI, 1.13-1.78]), whereas isolated diastolic hypertension was associated with increased risk of ischemic heart disease (HR, 1.26 [95% CI, 1.05-1.50]). Results were similar in nonsmoking women aged <35 years with normal weight and no diabetes mellitus during pregnancy.
Conclusions-Elevated blood pressure during pregnancy, regardless of type and even without known risk factors, signals high risk of later cardiovascular disease, chronic kidney disease, and diabetes mellitus. Clinical monitoring, risk factor evaluation, and early intervention could benefit women with hypertension in pregnancy. (Circulation. 2013;127:681-690.)
C1 [Maennistoe, Tuija; Mendola, Pauline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
[Vaarasmaki, Marja; Hartikainen, Anna-Liisa; Pouta, Anneli; Suvanto, Eila] Oulu Univ Hosp, Dept Obstet & Gynecol, Oulu, Finland.
[Jarvelin, Marjo-Riitta; Pouta, Anneli] Natl Inst Hlth & Welf, Dept Children Young People & Families, Helsinki, Finland.
[Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.
RP Mannisto, T (reprint author), NICHD, NIH, DESPR, Epidemiol Branch, 6100 Execut Blvd,7B05, Rockville, MD 20852 USA.
EM mannistoTI@mail.nih.gov
OI Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Mannisto,
Tuija/0000-0002-6382-9153; Mendola, Pauline/0000-0001-5330-2844
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development; Academy of Finland
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, and by the Academy of
Finland.
NR 41
TC 82
Z9 90
U1 5
U2 18
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 12
PY 2013
VL 127
IS 6
BP 681
EP 690
DI 10.1161/CIRCULATIONAHA.112.128751
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 088XR
UT WOS:000314871700012
PM 23401113
ER
PT J
AU Kotlyanskaya, L
McLinden, KA
Giniger, E
AF Kotlyanskaya, Lucy
McLinden, Kristina A.
Giniger, Edward
TI Of Proneurotrophins and Their Antineurotrophic Effects
SO SCIENCE SIGNALING
LA English
DT Article
ID DEVELOPING NEUROMUSCULAR SYNAPSES; NERVE GROWTH-FACTOR; RECEPTOR P75;
CELL-DEATH; BDNF; ROLES; GASTRULATION; RETRACTION; DPP; TRK
AB Neurotrophins perform essential processes throughout neural development. They signal through Trk receptor proteins, typically in association with a "low affinity" p75(NTR) pan-neurotrophin co-receptor. Neurotrophins are synthesized as proproteins; the pro domains are removed proteolytically to yield the mature, presumably functional forms of the neurotrophins. Recent findings, however, have revealed a positive role for the proneurotrophins themselves. The proproteins bind with high affinity to the p75(NTR) pan-neurotrophin receptor in the absence of Trks to initiate a separate set of signaling cascades that actively oppose the effects of the mature growth factors. These experiments suggest that the balance between pro- and mature neurotrophin plays a critical role in tuning downstream signaling. This view changes the neurotrophin field substantially, and also points to the broader idea that the potential activities of precursor proteins deserve a closer look.
C1 [Kotlyanskaya, Lucy; McLinden, Kristina A.; Giniger, Edward] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20854 USA.
[Kotlyanskaya, Lucy] Univ N Carolina, Neurobiol Curriculum, Chapel Hill, NC 27599 USA.
RP Giniger, E (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20854 USA.
EM ginigere@ninds.nih.gov
RI Giniger, Edward/C-1764-2015
OI Giniger, Edward/0000-0002-8340-6158
FU National Institute of Neurological Disorders and Stroke, NIH
[Z01-NS003013]; NSF
FX The authors were supported by the Basic Neuroscience Program in the
Intramural Research Program of the National Institute of Neurological
Disorders and Stroke, NIH (Z01-NS003013). L. K. was supported by a
predoctoral fellowship from the NSF.
NR 22
TC 3
Z9 3
U1 0
U2 7
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD FEB 12
PY 2013
VL 6
IS 262
AR pe6
DI 10.1126/scisignal.2003824
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 088ZP
UT WOS:000314877400001
PM 23405011
ER
PT J
AU Jinde, S
Zsiros, V
Nakazawa, K
AF Jinde, Seiichiro
Zsiros, Veronika
Nakazawa, Kazu
TI Hilar mossy cell circuitry controlling dentate granule cell excitability
SO FRONTIERS IN NEURAL CIRCUITS
LA English
DT Review
DE mossy cells; granule cells; excitability; epileptogenesis; lateral
inhibition; hippocampal mossy fibers; pattern separation; temporal lobe
epilepsy
ID TEMPORAL-LOBE EPILEPSY; CA3 PYRAMIDAL CELLS; INDUCED STATUS EPILEPTICUS;
RAT HIPPOCAMPAL SLICES; PATTERN SEPARATION; FASCIA-DENTATA; INHIBITORY
INTERNEURONS; IN-VIVO; SYNAPTIC REORGANIZATION; FEEDFORWARD INHIBITION
AB Glutamatergic hilar mossy cells of the dentate gyrus can either excite or inhibit distant granule cells, depending on whether their direct excitatory projections to granule cells or their projections to local inhibitory interneurons dominate. However, it remains controversial whether the net effect of mossy cell loss is granule cell excitation or inhibition. Clarifying this controversy has particular relevance to temporal lobe epilepsy, which is marked by dentate granule cell hyperexcitability and extensive loss of dentate hilar mossy cells. Two diametrically opposed hypotheses have been advanced to explain this granule cell hyperexcitability-the "dormant basket cell" and the "irritable mossy cell" hypotheses. The "dormant basket cell" hypothesis proposes that mossy cells normally exert a net inhibitory effect on granule cells and therefore their loss causes dentate granule cell hyperexcitability. The "irritable mossy cell" hypothesis takes the opposite view that mossy cells normally excite granule cells and that the surviving mossy cells in epilepsy increase their activity, causing granule cell excitation. The inability to eliminate mossy cells selectively has made it difficult to test these two opposing hypotheses. To this end, we developed a transgenic toxin-mediated, mossy cell-ablation mouse line. Using these mutants, we demonstrated that the extensive elimination of hilar mossy cells causes granule cell hyperexcitability, although the mossy cell loss observed appeared insufficient to cause clinical epilepsy. In this review, we focus on this topic and also suggest that different interneuron populations may mediate mossy cell-induced translamellar lateral inhibition and intralamellar recurrent inhibition. These unique local circuits in the dentate hilar region may be centrally involved in the functional organization of the dentate gyrus.
C1 [Jinde, Seiichiro] Univ Tokyo, Dept Neuropsychiat, Grad Sch Med, Tokyo, Japan.
[Zsiros, Veronika; Nakazawa, Kazu] NIMH, Unit Genet Cognit & Behav, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Nakazawa, K (reprint author), NIMH, Unit Genet Cognit & Behav, NIH, Dept Hlth & Human Serv, 35 Convent Dr, Bethesda, MD 20892 USA.
EM nakazawk@mail.nih.gov
RI Nakazawa, Kazutoshi/J-6195-2015
OI Nakazawa, Kazutoshi/0000-0001-5699-9093
FU NIMH; Ministry of Education, Culture, Sports, Science, and Technology,
Japan [22591274]; Japan Society for the Promotion of Science (JSPS)
FX We thank Stefan Kolata for his critical reading of this manuscript. This
research was supported by the Intramural Research Programs of the NIMH.
This research was partially supported by the Grant-in-Aid for Scientific
Research of Ministry of Education, Culture, Sports, Science, and
Technology, Japan (Grant number: 22591274). Seiichiro Jinde was
supported in part by a Japan Society for the Promotion of Science (JSPS)
fellowship.
NR 87
TC 23
Z9 24
U1 0
U2 21
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5110
J9 FRONT NEURAL CIRCUIT
JI Front. Neural Circuits
PD FEB 12
PY 2013
VL 7
AR 14
DI 10.3389/fncir.2013.00014
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 088LU
UT WOS:000314836800001
PM 23407806
ER
PT J
AU Absinta, M
Sati, P
Gaitan, M
Maggi, P
Cortese, I
Filippi, M
Reich, D
AF Absinta, Martina
Sati, Pascal
Gaitan, Maria
Maggi, Pietro
Cortese, Irene
Filippi, Massimo
Reich, Daniel
TI Architectural Development of Acute MS Lesions at 7T Phase Contrast
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Absinta, Martina; Sati, Pascal; Gaitan, Maria; Maggi, Pietro; Cortese, Irene; Reich, Daniel] NINDS, NIH, Bethesda, MD 20892 USA.
[Filippi, Massimo] Ist Sci San Raffaele, Inst Expt Neurol, Neuroimaging Res Unit, I-20132 Milan, Italy.
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA S21005
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068606072
ER
PT J
AU Anderson, C
Biffi, A
Nalls, M
Devan, W
Schwab, K
Ayres, A
Valant, V
Ross, O
Rost, N
Saxena, R
Viswanathan, A
Worrall, B
Brott, T
Goldstein, J
Brown, D
Broderick, J
Norrving, B
Greenberg, S
Silliman, S
Hansen, B
Tirschwell, D
Lindgren, A
Slowik, A
Schmidt, R
Selim, M
Gonzalez, JR
Montaner, J
Singleton, A
Kidwell, C
Woo, D
Furie, K
Meschia, J
Rosand, J
AF Anderson, Christopher
Biffi, Alessandro
Nalls, Michael
Devan, William
Schwab, Kristin
Ayres, Alison
Valant, Valerie
Ross, Owen
Rost, Natalia
Saxena, Richa
Viswanathan, Anand
Worrall, Bradford
Brott, Thomas
Goldstein, Joshua
Brown, Devin
Broderick, Joseph
Norrving, Bo
Greenberg, Steven
Silliman, Scott
Hansen, Bjorn
Tirschwell, David
Lindgren, Arne
Slowik, Agnieszka
Schmidt, Reinhold
Selim, Magdy
Roquer Gonzalez, Jaume
Montaner, Joan
Singleton, Andrew
Kidwell, Chelsea
Woo, Daniel
Furie, Karen
Meschia, James
Rosand, Jonathan
TI Common Variants within Oxidative Phosphorylation Genes Influence Risk of
Ischemic Stroke and Intracerebral Hemorrhage
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Anderson, Christopher; Biffi, Alessandro; Devan, William; Schwab, Kristin; Ayres, Alison; Valant, Valerie; Rost, Natalia; Saxena, Richa; Viswanathan, Anand; Goldstein, Joshua; Greenberg, Steven; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Nalls, Michael; Singleton, Andrew] NIA, Bethesda, MD 20892 USA.
[Ross, Owen; Brott, Thomas; Meschia, James] Mayo Clin, Jacksonville, FL 32224 USA.
[Worrall, Bradford] Univ Virginia, Charlottesville, VA USA.
[Brown, Devin] Univ Michigan, Ann Arbor, MI 48109 USA.
[Broderick, Joseph; Woo, Daniel] Univ Cincinnati, Cincinnati, OH USA.
[Norrving, Bo; Hansen, Bjorn; Lindgren, Arne] Lund Univ, Lund, Sweden.
[Silliman, Scott] Univ Florida, Jacksonville, FL USA.
[Tirschwell, David] Univ Washington, Seattle, WA 98195 USA.
[Slowik, Agnieszka] Jagiellonian Univ, Krakow, Poland.
[Schmidt, Reinhold] Graz Univ, St Radegund, Austria.
[Selim, Magdy] BIDMC, Boston, MA USA.
[Roquer Gonzalez, Jaume] Hosp del Mar, Barcelona, Spain.
[Montaner, Joan] Univ Vall Dhebron, Barcelona, Spain.
[Kidwell, Chelsea] Georgetown Univ, Washington, DC USA.
[Furie, Karen] Brown Univ, Providence, RI 02912 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA S42002
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068606203
ER
PT J
AU Anderson, C
Biffi, A
Nalls, M
Devan, W
Schwab, K
Ayres, A
Valant, V
Ross, O
Rost, N
Saxena, R
Viswanathan, A
Worrall, B
Brott, T
Goldstein, J
Brown, D
Broderick, J
Norrving, B
Greenberg, S
Silliman, S
Hansen, B
Tirschwell, D
Lindgren, A
Slowik, A
Schmidt, R
Selim, M
Gonzalez, JR
Montaner, J
Singleton, A
Kidwell, C
Woo, D
Furie, K
Meschia, J
Rosand, J
AF Anderson, Christopher
Biffi, Alessandro
Nalls, Michael
Devan, William
Schwab, Kristin
Ayres, Alison
Valant, Valerie
Ross, Owen
Rost, Natalia
Saxena, Richa
Viswanathan, Anand
Worrall, Bradford
Brott, Thomas
Goldstein, Joshua
Brown, Devin
Broderick, Joseph
Norrving, Bo
Greenberg, Steven
Silliman, Scott
Hansen, Bjorn
Tirschwell, David
Lindgren, Arne
Slowik, Agnieszka
Schmidt, Reinhold
Selim, Magdy
Roquer Gonzalez, Jaume
Montaner, Joan
Singleton, Andrew
Kidwell, Chelsea
Woo, Daniel
Furie, Karen
Meschia, James
Rosand, Jonathan
TI Common Variants within Oxidative Phosphorylation Genes Influence Risk of
Ischemic Stroke and Intracerebral Hemorrhage
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Anderson, Christopher; Biffi, Alessandro; Devan, William; Schwab, Kristin; Ayres, Alison; Valant, Valerie; Rost, Natalia; Saxena, Richa; Viswanathan, Anand; Goldstein, Joshua; Greenberg, Steven; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Nalls, Michael] NIA, Bethesda, MD 20892 USA.
[Ross, Owen; Brott, Thomas; Meschia, James] Mayo Clin, Jacksonville, FL 32224 USA.
[Worrall, Bradford] Univ Virginia, Charlottesville, VA USA.
[Brown, Devin] Univ Michigan, Ann Arbor, MI 48109 USA.
[Broderick, Joseph; Woo, Daniel] Univ Cincinnati, Cincinnati, OH USA.
[Norrving, Bo; Hansen, Bjorn; Lindgren, Arne] Lund Univ, Lund, Sweden.
[Silliman, Scott] Univ Florida, Jacksonville, FL USA.
[Tirschwell, David] Univ Washington, Seattle, WA 98195 USA.
[Slowik, Agnieszka] Jagiellonian Univ, Krakow, Poland.
[Schmidt, Reinhold] Graz Univ, St Radegund, Austria.
[Selim, Magdy] BIDMC, Boston, MA USA.
[Roquer Gonzalez, Jaume] Hosp del Mar, Barcelona, Spain.
[Montaner, Joan] Univ Vall Dhebron, Barcelona, Spain.
[Kidwell, Chelsea] Georgetown Univ, Washington, DC USA.
[Furie, Karen] Brown Univ, Providence, RI 02912 USA.
RI Montaner, Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015
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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA IN71001
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068600087
ER
PT J
AU Bagnato, F
Hametner, S
Ikonomidou, V
Van Gelderen, P
Cantor, F
Ohayon, J
Richert, N
Lassmann, H
Duyn, J
Yao, B
AF Bagnato, Francesca
Hametner, Simon
Ikonomidou, Vasiliki
Van Gelderen, Peter
Cantor, Fredric
Ohayon, Joan
Richert, Nancy
Lassmann, Hans
Duyn, Jeff
Yao, Bing
TI Slowly Expanding Lesions in Multiple Sclerosis: An In Vivo Demonstration
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Bagnato, Francesca] Univ Maryland, Baltimore, MD 21201 USA.
[Hametner, Simon; Lassmann, Hans] Univ Vienna, Vienna, Austria.
[Ikonomidou, Vasiliki] George Mason Univ, Dept Elect & Comp Engn, Fairfax, MD USA.
[Van Gelderen, Peter; Cantor, Fredric; Ohayon, Joan; Duyn, Jeff; Yao, Bing] NIH, Bethesda, MD 20892 USA.
[Richert, Nancy] Biogen Inc, Cambridge, MA 02142 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA S21006
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068606073
ER
PT J
AU Benninger, D
Lin, P
Kida, T
Iseki, K
Wasaka, T
Bai, O
Hallett, M
AF Benninger, David
Lin, Peter
Kida, Tetsuo
Iseki, Kazumi
Wasaka, Toshi
Bai, Ou
Hallett, Mark
TI Correlation of High-Frequency Oscillations in Focal Hand Dystonia with
Therapeutic Response after Botulinum Toxin Treatment
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Benninger, David] CHU Vaudois, Dept Neurosci Clin, Serv Neurol, Lausanne, Switzerland.
[Lin, Peter] NIH, Rockville, MD USA.
[Kida, Tetsuo; Wasaka, Toshi] NINDS, Human Motor Control Sect, Med Neurol Branch, Bethesda, MD 20892 USA.
[Iseki, Kazumi; Bai, Ou] NIH, Bethesda, MD 20892 USA.
[Hallett, Mark] NINDS, NIH, Bethesda, MD 20892 USA.
RI Benninger, David/A-8157-2015
OI Benninger, David/0000-0002-1049-9533
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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P07194
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068605176
ER
PT J
AU Burke, A
Fischbeck, K
Grunseich, C
AF Burke, Ailbhe
Fischbeck, Kenneth
Grunseich, Christopher
TI Spironolactone Treatment in a Cell Culture Model of Spinal and Bulbar
Muscular Atrophy
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Burke, Ailbhe] UCL, London, England.
[Fischbeck, Kenneth] NINDS, NIH, Bethesda, MD 20892 USA.
[Grunseich, Christopher] NINDS, NIH, Columbia, 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P02174
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068601238
ER
PT J
AU Burke, A
Fischbeck, K
Grunseich, C
AF Burke, Ailbhe
Fischbeck, Kenneth
Grunseich, Christopher
TI Spironolactone Treatment in a Cell Culture Model of Spinal and Bulbar
Muscular Atrophy
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Burke, Ailbhe] UCL, London, England.
[Fischbeck, Kenneth] NINDS, NIH, Bethesda, MD 20892 USA.
[Grunseich, Christopher] NINDS, NIH, Columbia, 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA IN81003
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068600104
ER
PT J
AU Calvo, A
Cistaro, A
Pagani, M
Montuschi, A
Moglia, C
Canosa, A
Restagno, G
Traynor, B
Nobili, F
Carrara, G
Lopiano, L
Valentini, C
Chio, A
AF Calvo, Andrea
Cistaro, Angelina
Pagani, Marco
Montuschi, Anna
Moglia, Cristina
Canosa, Antonio
Restagno, Gabriella
Traynor, Bryan
Nobili, Flavio
Carrara, Giovanna
Lopiano, Leonardo
Valentini, Consuelo
Chio, Adriano
TI PET in in ALS Patients with C9ORF72 Mutations
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Calvo, Andrea; Montuschi, Anna; Moglia, Cristina; Canosa, Antonio; Lopiano, Leonardo; Chio, Adriano] Univ Turin, Dept Neurosci, Turin, Italy.
[Cistaro, Angelina] IRMET SpA, Positron Emiss Tomog Ctr, Turin, Italy.
[Pagani, Marco] CNR, Rome, Italy.
[Restagno, Gabriella] AO Citta Salute & Sci, Mol Genet Lab, Turin, Italy.
[Traynor, Bryan] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Nobili, Flavio] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Clin Neurophysiol Unit, Genoa, Italy.
[Carrara, Giovanna; Valentini, Consuelo] AO Citta Salute & Sci, Neuroradiol Unit, Turin, Italy.
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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P06131
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068604199
ER
PT J
AU Chen, HL
Guo, XG
Park, Y
Freedman, N
Shinha, R
Hollenbeck, A
Blair, A
AF Chen, Honglei
Guo, Xuguang
Park, Yikyung
Freedman, Neal
Shinha, Rashmi
Hollenbeck, Albert
Blair, Aaron
TI Sweetened-Beverages, Coffee, and Tea in Relation to Depression among
Older US Adults
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Chen, Honglei] NIEHS, Res Triangle Pk, NC 27709 USA.
[Guo, Xuguang] Westat Corp, Durham, NC USA.
[Park, Yikyung; Freedman, Neal; Shinha, Rashmi; Blair, Aaron] NCI, Rockville, MD USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P05122
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068603275
ER
PT J
AU Czarnecki, K
Toledo, R
Hallett, M
AF Czarnecki, Kathrin
Toledo, Ryan
Hallett, Mark
TI Heart Rate Variability and Cortisol Diurnal Profiles in Functional
Movement Disorder Patients
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Czarnecki, Kathrin; Toledo, Ryan; Hallett, Mark] NINDS, NIH, 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P03059
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068602028
ER
PT J
AU Flinders, A
Sanossian, N
Starkman, S
Liebeskind, D
Eckstein, M
Stratton, S
Pratt, F
Hamilton, S
Olivas, E
Chatfield, F
Conwit, R
Saver, J
AF Flinders, Abraham
Sanossian, Nerses
Starkman, Sidney
Liebeskind, David
Eckstein, Marc
Stratton, Samuel
Pratt, Frank
Hamilton, Scott
Olivas, Edgar
Chatfield, Fiona
Conwit, Robin
Saver, Jeffrey
TI Frequency and Speed of Early Antihypertensive Treatment of Severe
Hypertension in Acute Intracerebral Hemorrhage Patients in a Broad
Community Setting
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Flinders, Abraham; Sanossian, Nerses; Eckstein, Marc; Olivas, Edgar] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Starkman, Sidney; Liebeskind, David; Saver, Jeffrey] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA.
[Pratt, Frank] Los Angeles Cty Fire Dept, Torrance, CA USA.
[Hamilton, Scott] Stanford Univ, San Francisco, CA USA.
[Chatfield, Fiona] Fast Mag, Los Angeles, CA USA.
[Conwit, Robin] NINHS, NIH, Lutherville Timonium, 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA S07007
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068605376
ER
PT J
AU Flinders, A
Sanossian, N
Starkman, S
Liebeskind, D
Eckstein, M
Stratton, S
Pratt, F
Hamilton, S
Olivas, E
Chatfield, F
Conwit, R
Saver, J
AF Flinders, Abraham
Sanossian, Nerses
Starkman, Sidney
Liebeskind, David
Eckstein, Marc
Stratton, Samuel
Pratt, Frank
Hamilton, Scott
Olivas, Edgar
Chatfield, Fiona
Conwit, Robin
Saver, Jeffrey
TI Management of Early Severe Hypertension in Acute Intracerebral
Hemorrhage in Primary Stroke Centers vs. Non-Stroke Center Hospitals
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Flinders, Abraham] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Sanossian, Nerses; Eckstein, Marc; Olivas, Edgar] USC Keck Sch Med, Los Angeles, CA USA.
[Starkman, Sidney; Liebeskind, David; Saver, Jeffrey] UCLA Stroke Ctr, Los Angeles, CA USA.
[Stratton, Samuel] Orange Cty EMS Agcy, Santa Ana, CA USA.
[Pratt, Frank] Los Angeles Cty Fire Dept, Torrance, CA USA.
[Hamilton, Scott] Stanford Univ, Stanford, CA 94305 USA.
[Chatfield, Fiona] Fast Mag Coordinating Ctr, Los Angeles, CA USA.
[Conwit, Robin] NINHS, NIH, Lutherville Timonium, 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P01022
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068600179
ER
PT J
AU Gelber, R
Launer, L
Petrovitch, H
Masaki, K
Ross, W
White, L
AF Gelber, Rebecca
Launer, Lenore
Petrovitch, Helen
Masaki, Kamal
Ross, Web
White, Lon
TI Beta-Blocker Treatment of Hypertensive Older Persons Decreases Risk of
Cognitive Impairment: The HonoluluAsia Aging Study
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Gelber, Rebecca; Ross, Web] VA Pacific Isl Hlth Care Syst, Honolulu, HI USA.
[Launer, Lenore] NIA, Washington, DC USA.
[Petrovitch, Helen] VA Pacific Isl Hlth Care Syst, Kailua, HI USA.
[Masaki, Kamal; White, Lon] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P03094
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068602063
ER
PT J
AU Ghosh, P
Considine, E
Karp, B
Hallett, M
Lungu, C
Alter, K
AF Ghosh, Pritha
Considine, Elaine
Karp, Barbara
Hallett, Mark
Lungu, Codrin
Alter, Katharine
TI Features and Challenges in Runner's Dystonia
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Ghosh, Pritha; Considine, Elaine; Karp, Barbara; Hallett, Mark; Lungu, Codrin] NINDS, NIH, Bethesda, MD 20892 USA.
[Alter, Katharine] NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P07199
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068605181
ER
PT J
AU Ilieva, H
Ling, SC
Parone, P
Da Cruz, S
Tokunaga, S
Bui, N
Swing, D
Marsala, M
Tessarollo, L
Shaw, C
Cleveland, D
AF Ilieva, Hristelina
Ling, Shuo-Chien
Parone, Philippe
Da Cruz, Sandrine
Tokunaga, Seiya
Bui, Ngoc
Swing, Debbie
Marsala, Martin
Tessarollo, Lino
Shaw, Christopher
Cleveland, Don
TI Dose-Dependent and Mutant Enhanced Neurotoxicity in Mice Expressing Wild
Type or ALS-Linked Mutants of FUS/TLS
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Ilieva, Hristelina] Methodist Hosp, Dept Neurol, Houston, TX 77030 USA.
[Ling, Shuo-Chien; Parone, Philippe; Da Cruz, Sandrine; Tokunaga, Seiya; Bui, Ngoc] Ludwig Inst Canc Res, La Jolla, CA USA.
[Swing, Debbie] NCI, Frederick, MD 21701 USA.
[Marsala, Martin] Univ Calif San Diego, Dept Anesthesiol, La Jolla, CA 92093 USA.
[Tessarollo, Lino] NCI, Neural Dev Sect, Frederick, MD 21701 USA.
[Shaw, Christopher] MRC Ctr Neurodegenerat Res, London, England.
[Cleveland, Don] Ludwig Inst Canc Res, La Jolla, CA 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA S06006
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068605369
ER
PT J
AU Kapogiannis, D
AF Kapogiannis, Dimitrios
TI Precuneus Glucose Reflects CSF A beta 42 in Early Alzheimer's Disease
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Kapogiannis, Dimitrios] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P06043
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068604111
ER
PT J
AU Kearney, M
Ecklund, D
Simpson, E
Bosch, M
Sweet, B
Jackson, K
Mahoney, K
McCourt, M
Thornell, B
Titus, S
Soodoo, N
O'Brien, J
Gloer, K
Costigan, M
Logsden-Sackett, N
Huff, T
Shefner, J
Gutmann, L
Clarke, W
Torner, J
Long, J
Chaloner, K
Bayman, E
McNeil, D
Koroshetz, W
Kaufmann, P
Cudkowicz, M
Coffey, C
AF Kearney, Marianne
Ecklund, Dixie
Simpson, Elizabeth
Bosch, Michael
Sweet, Bryan
Jackson, Katherine
Mahoney, Katy
McCourt, Michelle
Thornell, Brenda
Titus, Sarah
Soodoo, Natasha
O'Brien, Janice
Gloer, Katherine
Costigan, Michele
Logsden-Sackett, Nyla
Huff, Trevis
Shefner, Jeremy
Gutmann, Laurie
Clarke, William
Torner, James
Long, Jeffrey
Chaloner, Kathryn
Bayman, Emine
McNeil, Dawn
Koroshetz, Walter
Kaufmann, Petra
Cudkowicz, Merit
Coffey, Christopher
TI Network for Excellence in Neuroscience Clinical Trials, NeuroNEXT:
Concept to Implementation
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Kearney, Marianne; Simpson, Elizabeth; Mahoney, Katy; McCourt, Michelle; Thornell, Brenda; Titus, Sarah; Soodoo, Natasha; O'Brien, Janice; Cudkowicz, Merit] MGH, Charlestown, MA USA.
[Ecklund, Dixie; Bosch, Michael; Gloer, Katherine; Costigan, Michele; Logsden-Sackett, Nyla; Huff, Trevis; Clarke, William; Torner, James; Long, Jeffrey; Chaloner, Kathryn; Bayman, Emine; Coffey, Christopher] U Iowa, Iowa City, IA USA.
[Sweet, Bryan; Jackson, Katherine] Massachusetts Gen Hosp, Charlestown, MA USA.
[Shefner, Jeremy] SUNY Upstate Med Ctr, Syracuse, NY USA.
[Gutmann, Laurie] W Virginia Univ, Morgantown, WV 26506 USA.
[McNeil, Dawn; Koroshetz, Walter] NINDS, Bethesda, MD 20892 USA.
[Kaufmann, Petra] NINDS, Rockville, MD 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P04245
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068603134
ER
PT J
AU Lu-Emerson, C
Snuderl, M
Kirkpatrick, N
Goveia, J
Davidson, C
Huang, Y
Riedemann, L
Ivy, P
Ancukiewicz, M
Stemmer-Rachamimov, A
Batchelor, T
Jain, R
AF Lu-Emerson, Christine
Snuderl, Matija
Kirkpatrick, Nathaniel
Goveia, Jermaine
Davidson, Christian
Huang, Yuhui
Riedemann, Lars
Ivy, Percy
Ancukiewicz, Marek
Stemmer-Rachamimov, Anat
Batchelor, Tracy
Jain, Rakesh
TI Direct Evidence That Increase in Tumor-Associated Macrophages (TAMs)
after Antiangiogenic Therapy Is Associated with Poor Survival in
Recurrent Glioblastoma (GBM) Patients
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Lu-Emerson, Christine] Massachusetts Gen Hosp, Dept Neurooncol, Boston, MA 02114 USA.
[Snuderl, Matija; Batchelor, Tracy] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kirkpatrick, Nathaniel; Goveia, Jermaine; Huang, Yuhui; Riedemann, Lars; Ancukiewicz, Marek; Jain, Rakesh] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Davidson, Christian; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Ivy, Percy] NCI, Invest Drug Branch, Rockville, MD USA.
RI Riedemann, Lars/J-5725-2014
OI Riedemann, Lars/0000-0002-9510-1845
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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA S35001
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068606159
ER
PT J
AU Lu-Emerson, C
Snuderl, M
Kirkpatrick, N
Goveia, J
Davidson, C
Huang, YH
Riedemann, L
Ivy, P
Ancukiewicz, M
Stemmer-Rachamimov, A
Batchelor, T
Jain, R
AF Lu-Emerson, Christine
Snuderl, Matija
Kirkpatrick, Nathaniel
Goveia, Jermaine
Davidson, Christian
Huang, Yuhui
Riedemann, Lars
Ivy, Percy
Ancukiewicz, Marek
Stemmer-Rachamimov, Anat
Batchelor, Tracy
Jain, Rakesh
TI Direct Evidence That Increase in Tumor-Associated Macrophages (TAMs)
after Antiangiogenic Therapy Is Associated with Poor Survival in
Recurrent Glioblastoma (GBM) Patients
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Lu-Emerson, Christine] Massachusetts Gen Hosp, Dept Neurooncol, Boston, MA 02114 USA.
[Snuderl, Matija; Batchelor, Tracy] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kirkpatrick, Nathaniel; Goveia, Jermaine; Huang, Yuhui; Riedemann, Lars; Ancukiewicz, Marek; Jain, Rakesh] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Davidson, Christian; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Ivy, Percy] NCI, Invest Drug Branch, Rockville, 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA IN102001
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068600138
ER
PT J
AU Lublin, F
Cofield, S
Cutter, G
Salter, A
Wang, J
Conwit, R
Narayana, P
Nelson, F
Gustafson, T
Wolinsky, J
AF Lublin, Fred
Cofield, Stacey
Cutter, Gary
Salter, Amber
Wang, Jing
Conwit, Robin
Narayana, Ponnada
Nelson, Flavia
Gustafson, Tarah
Wolinsky, Jerry
TI Relapse Activity in the CombiRx Trial: Blinded, 7-Year Extension Results
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Lublin, Fred; Gustafson, Tarah] Mt Sinai Sch Med, New York, NY USA.
[Cofield, Stacey; Cutter, Gary; Salter, Amber; Wang, Jing] Univ Alabama Birmingham, Birmingham, AL USA.
[Conwit, Robin] NINDS, NIH, Lutherville Timonium, MD USA.
[Narayana, Ponnada; Nelson, Flavia; Wolinsky, Jerry] Univ Texas Hlth Sci Ctr Houston, 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA S01002
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068605334
ER
PT J
AU Lublin, F
Cofield, S
Cutter, G
Salter, A
Wang, J
Conwit, R
Narayana, P
Nelson, F
Gustafson, T
Wolinsky, J
AF Lublin, Fred
Cofield, Stacey
Cutter, Gary
Salter, Amber
Wang, Jing
Conwit, Robin
Narayana, Ponnada
Nelson, Flavia
Gustafson, Tarah
Wolinsky, Jerry
TI EDSS Changes in CombiRx: Blinded, 7-Year Extension Results for
Progression and Improvement
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Lublin, Fred; Gustafson, Tarah] Mt Sinai Sch Med, New York, NY USA.
[Cofield, Stacey; Cutter, Gary; Salter, Amber; Wang, Jing] Univ Alabama Birmingham, Birmingham, AL USA.
[Conwit, Robin] NINDS, NIH, Lutherville Timonium, MD USA.
[Narayana, Ponnada; Nelson, Flavia; Wolinsky, Jerry] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P04121
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068603010
ER
PT J
AU Masdeu, J
Gonzalez-Pinto, A
Matute, C
de Azua, SR
Palomino, A
De Leon, J
Dalmau, J
AF Masdeu, Joseph
Gonzalez-Pinto, Ana
Matute, Carlos
Ruiz de Azua, Sonia
Palomino, Aitor
De Leon, Jose
Dalmau, Josep
TI Absence of Serum IgG Antibodies Against the NR1 Subunit of the NMDA
Receptor in Patients with Schizophrenia
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Masdeu, Joseph] NIH, Bethesda, MD 20892 USA.
[Gonzalez-Pinto, Ana; Ruiz de Azua, Sonia] Univ Hosp Alava, Vitoria, Spain.
[Matute, Carlos; Palomino, Aitor] Univ Basque Country, EHU, Leioa, Spain.
[De Leon, Jose] Eastern State Hosp, Mental Hlth Res Ctr, Lexington, KY USA.
[Dalmau, Josep] Univ Barcelona, Barcelona, Spain.
RI de Leon, Jose/F-2709-2013
OI de Leon, Jose/0000-0002-7756-2314
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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P06062
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068604130
ER
PT J
AU Oh, J
Saidha, S
Chen, M
Smith, S
Prince, J
Jones, C
Van Zijl, P
Diener-West, M
Reich, D
Calabresi, P
AF Oh, Jiwon
Saidha, Shiv
Chen, Min
Smith, Seth
Prince, Jerry
Jones, Craig
Van Zijl, Peter
Diener-West, Marie
Reich, Daniel
Calabresi, Peter
TI Relative Clinical Utility of Quantitative MRI Measures in the Spinal
Cord in Multiple Sclerosis Patients
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Oh, Jiwon; Chen, Min; Prince, Jerry; Jones, Craig; Van Zijl, Peter; Diener-West, Marie; Calabresi, Peter] Johns Hopkins Univ, Baltimore, MD USA.
[Saidha, Shiv] Johns Hopkins Univ, Dublin, Ireland.
[Smith, Seth] Vanderbilt Univ, Nashville, TN 37235 USA.
[Reich, Daniel] NIH, Bethesda, MD 20892 USA.
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA PD6006
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068605311
ER
PT J
AU Oh, J
Seigo, M
Saidha, S
Sotirchos, E
Zackowski, K
Chen, M
Prince, J
Diener-West, M
Calabresi, P
Reich, D
AF Oh, Jiwon
Seigo, Michaela
Saidha, Shiv
Sotirchos, Elias
Zackowski, Kathleen
Chen, Min
Prince, Jerry
Diener-West, Marie
Calabresi, Peter
Reich, Daniel
TI Normalization of the Spinal Cord in Multiple Sclerosis
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Oh, Jiwon; Seigo, Michaela; Sotirchos, Elias; Zackowski, Kathleen; Chen, Min; Prince, Jerry; Diener-West, Marie; Calabresi, Peter] Johns Hopkins Univ, Baltimore, MD USA.
[Saidha, Shiv] Johns Hopkins Univ, Dublin, Ireland.
[Reich, Daniel] NIH, Bethesda, MD 20892 USA.
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P06106
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068604174
ER
PT J
AU Patel, R
Starkman, S
Hamilton, S
Craig, S
Yanes, A
Conwit, R
Saver, J
AF Patel, Richa
Starkman, Sidney
Hamilton, Scott
Craig, Sharon
Yanes, Anna
Conwit, Robin
Saver, Jeffrey
TI Improving the Reliability of Rankin Scale Stroke Disability Grading in
Clinical Trials and Clinical Practice: The Rankin Focused Assessment -
Ambulation (RFA - A)
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Patel, Richa] Univ Calif Los Angeles, Stroke Ctr, Laguna Niguel, CA USA.
[Starkman, Sidney; Saver, Jeffrey] Univ Calif Los Angeles, Los Angeles, CA USA.
[Craig, Sharon; Yanes, Anna] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA.
[Conwit, Robin] NINDS, NIH, Lutherville Timonium, 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA S32003
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068606144
ER
PT J
AU Reich-Slotky, R
Andrews, J
Buchsbaum, R
Levy, D
Kaufmann, P
Thompson, J
AF Reich-Slotky, Ronit
Andrews, Jinsy
Buchsbaum, Richard
Levy, Diane
Kaufmann, Petra
Thompson, John
TI Body Mass Index (BMI) as Predictor of ALSFRS-r Score Decline in ALS
Patients
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Reich-Slotky, Ronit] Columbia Univ, New York, NY USA.
[Andrews, Jinsy] Hosp Special Care, New Britain, CT USA.
[Buchsbaum, Richard; Levy, Diane; Thompson, John] Columbia Univ, Dept Biostat, New York, NY USA.
[Kaufmann, Petra] NIH, Rockville, MD 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P07085
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068605067
ER
PT J
AU Richardson, SP
Beck, S
Bliem, B
Hallett, M
AF Richardson, Sarah Pirio
Beck, Sandra
Bliem, Barbara
Hallett, Mark
TI A Potential Biomarker for Focal Dystonia: Abnormal Dorsal Premotor-Motor
Inhibition in Writer's Cramp
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Richardson, Sarah Pirio] Univ New Mexico, Albuquerque, NM 87131 USA.
[Beck, Sandra] Univ Freiburg, D-79106 Freiburg, Germany.
[Bliem, Barbara; Hallett, Mark] NINDS, NIH, HMCS, 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA S33006
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068606153
ER
PT J
AU Ross, W
Inaba, M
Masaki, K
Abbott, R
Fong, KO
Bell, C
Petrovitch, H
Tanner, C
Launer, L
White, L
AF Ross, Web
Inaba, Michiko
Masaki, Kamal
Abbott, Robert
Fong, Ka-on
Bell, Christina
Petrovitch, Helen
Tanner, Caroline
Launer, Lenore
White, Lon
TI Association of Slow Reaction Time with Future Risk of Parkinson's
Disease in the Honolulu-Asia Aging Study
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Ross, Web] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA.
[Inaba, Michiko; Masaki, Kamal; Bell, Christina] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA.
[Abbott, Robert] Univ Virginia, Sch Med, Div Biostat, Charlottesville, VA 22908 USA.
[Fong, Ka-on] Kuakini Med Ctr, Honolulu, HI USA.
[Petrovitch, Helen; White, Lon] Pacific Hlth Res & Educ Inst, Kailua, HI USA.
[Tanner, Caroline] Parkinsons Inst, Sunnyvale, CA USA.
[Launer, Lenore] NIA, NIH, Washington, DC 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P03063
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068602032
ER
PT J
AU Santos-Modesitt, W
Yaffe, K
Byers, A
Penninx, B
Simonsick, E
Satterfield, S
Cauley, J
Harris, T
Metti, A
Patel, K
Koster, A
Barnes, D
AF Santos-Modesitt, Wendy
Yaffe, Kristine
Byers, Amy
Penninx, Brenda
Simonsick, Eleanor
Satterfield, Suzanne
Cauley, Jane
Harris, Tamara
Metti, Andrea
Patel, Kushang
Koster, Annemarie
Barnes, Deborah
TI Cross Sectional and Longitudinal Associations between Serum
Brain-Derived Neurotrophic Factor (sBDNF) and Depressive Symptoms - The
Health, Aging and Body Composition (Health ABC) Study
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Santos-Modesitt, Wendy; Yaffe, Kristine; Byers, Amy; Barnes, Deborah] Univ Calif San Francisco, San Francisco Vet Affairs, San Francisco, CA 94143 USA.
[Penninx, Brenda] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
[Simonsick, Eleanor] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Cauley, Jane; Metti, Andrea] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Harris, Tamara] NIA, Bethesda, MD 20892 USA.
[Patel, Kushang] Univ Washington, Seattle, WA 98195 USA.
[Koster, Annemarie] Maastricht Univ, Maastricht, Netherlands.
RI Koster, Annemarie/E-7438-2010
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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P05113
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068603266
ER
PT J
AU Von Geldern, G
Nath, A
AF Von Geldern, Gloria
Nath, Avindra
TI Abnormal Brain Pathology in Virologically Controlled HIV-Infected
Individuals
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Von Geldern, Gloria; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Washington, DC 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA S38003
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068606179
ER
PT J
AU White, L
Gelber, R
Launer, L
Zarow, C
Sonnen, J
Uyehara-Lock, J
Masaki, K
Ross, G
Petrovitch, H
AF White, Lon
Gelber, Rebecca
Launer, Lenore
Zarow, Chris
Sonnen, Joshua
Uyehara-Lock, Jane
Masaki, Kamal
Ross, George
Petrovitch, Helen
TI Beta Blocker Treatment of Hypertensive Older Persons Ameliorates the
Brain Lesions of Dementia Measured at Autopsy: The Honolulu-Asia Aging
Study
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [White, Lon; Petrovitch, Helen] Pacific Hlth Res & Educ Inst, Honolulu, HI USA.
[Gelber, Rebecca; Ross, George] Hawaii Dept Vet Affairs, Honolulu, HI USA.
[Launer, Lenore] NIA, Lab Epidemiol Demog & Biometry, NIH, Washington, DC USA.
[Zarow, Chris] Univ So Calif, Sch Med, Downey, CA USA.
[Sonnen, Joshua] Univ Washington, Sch Med, Seattle, WA USA.
[Uyehara-Lock, Jane; Masaki, Kamal] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA S44005
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068606220
ER
PT J
AU Wolinsky, J
Salter, A
Narayana, P
Datta, S
Nelson, F
Cofield, S
Cutter, G
Conwit, R
Gustafson, T
Lublin, F
AF Wolinsky, Jerry
Salter, Amber
Narayana, Ponnada
Datta, Sushmita
Nelson, Flavia
Cofield, Stacey
Cutter, Gary
Conwit, Robin
Gustafson, Tarah
Lublin, Fred
TI MRI Outcomes in CombiRx: Blinded, 7-Year Extension Results
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Wolinsky, Jerry; Narayana, Ponnada; Datta, Sushmita; Nelson, Flavia] Univ Texas HSCH, Houston, TX USA.
[Salter, Amber; Cofield, Stacey; Cutter, Gary] Univ Alabama Birmingham, Birmingham, AL USA.
[Conwit, Robin] NINDS, NIH, Lutherville Timonium, MD USA.
[Gustafson, Tarah; Lublin, Fred] Mt Sinai Sch Med, New York, 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA S01003
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068605335
ER
PT J
AU Zhao, E
Zhang, W
Peddada, S
Chen, HL
AF Zhao, Edward
Zhang, Wen
Peddada, Shyamal
Chen, Honglei
TI Meta-Analysis on the Prevalence of Selected Premotor Symptoms of
Parkinson Disease before and after Diagnosis
SO NEUROLOGY
LA English
DT Meeting Abstract
CT 65th Annual Meeting of the American-Academy-of-Neurology (AAN)
CY MAR 16-23, 2013
CL San Diego, CA
SP Amer Acad Neurol
C1 [Zhao, Edward; Zhang, Wen; Peddada, Shyamal] NIEHS RTP, Res Triangle Pk, NC USA.
[Chen, Honglei] NIEHS, Res Triangle Pk, NC 27709 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 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 12
PY 2013
VL 80
SU S
MA P06097
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AB8VR
UT WOS:000332068604165
ER
PT J
AU Sani, MA
Weber, DK
Delaglio, F
Separovic, F
Gehman, JD
AF Sani, Marc-Antoine
Weber, Daniel K.
Delaglio, Frank
Separovic, Frances
Gehman, John D.
TI A practical implementation of de-Pake-ing via weighted Fourier
transformation
SO PEERJ
LA English
DT Article
DE dePake; NMRPipe; Membrane perturbation; Lipid biophysics; Deuterium NMR
AB We provide an NMRPipe macro to meet an increasing need in membrane biophysics for facile de-Pake-ing of axially symmetric deuterium, and to an extent phosphorous, static lineshapes. The macro implements the development of McCabe & Wassall (1997), and is run as a simple replacement for the usual Fourier transform step in an NMRPipe processing procedure.
C1 [Sani, Marc-Antoine; Weber, Daniel K.; Separovic, Frances; Gehman, John D.] Univ Melbourne, Inst Bio21, Sch Chem, Melbourne, Vic 3010, Australia.
[Delaglio, Frank] NIDDK, Phys Chem Lab, NIH, Bethesda, MD USA.
RP Gehman, JD (reprint author), Univ Melbourne, Inst Bio21, Sch Chem, Melbourne, Vic 3010, Australia.
EM jgehman@unimelb.edu.au
RI Separovic, Frances/D-9698-2011;
OI Separovic, Frances/0000-0002-6484-2763; Gehman, John
D/0000-0002-2599-6292; Weber, Daniel/0000-0001-8400-767X; Sani,
Marc-antoine/0000-0003-3284-2176
FU Australian Research Council Future Fellowship
FX JD Gehman is funded under an Australian Research Council Future
Fellowship. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 28
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U2 6
PU PEERJ INC
PI LONDON
PA 341-345 OLD ST, THIRD FLR, LONDON, EC1V 9LL, ENGLAND
SN 2167-8359
J9 PEERJ
JI PeerJ
PD FEB 12
PY 2013
VL 1
AR e30
DI 10.7717/peerj.30
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36AF
UT WOS:000209185300025
PM 23638366
ER
PT J
AU Cohen, JM
Dlamini, S
Novotny, JM
Kandula, D
Kunene, S
Tatem, AJ
AF Cohen, Justin M.
Dlamini, Sabelo
Novotny, Joseph M.
Kandula, Deepika
Kunene, Simon
Tatem, Andrew J.
TI Rapid case-based mapping of seasonal malaria transmission risk for
strategic elimination planning in Swaziland
SO MALARIA JOURNAL
LA English
DT Article
ID SUB-SAHARAN AFRICA; PLASMODIUM-FALCIPARUM; SPECIES DISTRIBUTIONS;
WETNESS INDEXES; DISEASE BURDEN; ENDEMICITY; PREDICTION; REGRESSION;
HIGHLANDS; HABITAT
AB Background: As successful malaria control programmes move towards elimination, they must identify residual transmission foci, target vector control to high-risk areas, focus on both asymptomatic and symptomatic infections, and manage importation risk. High spatial and temporal resolution maps of malaria risk can support all of these activities, but commonly available malaria maps are based on parasite rate, a poor metric for measuring malaria at extremely low prevalence. New approaches are required to provide case-based risk maps to countries seeking to identify remaining hotspots of transmission while managing the risk of transmission from imported cases.
Methods: Household locations and travel histories of confirmed malaria patients during 2011 were recorded through routine surveillance by the Swaziland National Malaria Control Programme for the higher transmission months of January to April and the lower transmission months of May to December. Household locations for patients with no travel history to endemic areas were compared against a random set of background points sampled proportionate to population density with respect to a set of variables related to environment, population density, vector control, and distance to the locations of identified imported cases. Comparisons were made separately for the high and low transmission seasons. The Random Forests regression tree classification approach was used to generate maps predicting the probability of a locally acquired case at 100 m resolution across Swaziland for each season.
Results: Results indicated that case households during the high transmission season tended to be located in areas of lower elevation, closer to bodies of water, in more sparsely populated areas, with lower rainfall and warmer temperatures, and closer to imported cases than random background points (all p < 0.001). Similar differences were evident during the low transmission season. Maps from the fit models suggested better predictive ability during the high season. Both models proved useful at predicting the locations of local cases identified in 2012.
Conclusions: The high-resolution mapping approaches described here can help elimination programmes understand the epidemiology of a disappearing disease. Generating case-based risk maps at high spatial and temporal resolution will allow control programmes to direct interventions proactively according to evidence-based measures of risk and ensure that the impact of limited resources is maximized to achieve and maintain malaria elimination.
C1 [Cohen, Justin M.; Novotny, Joseph M.; Kandula, Deepika] Clinton Hlth Access Initiat, Boston, MA USA.
[Dlamini, Sabelo; Kunene, Simon] Natl Malaria Control Programme, Mbabane, Swaziland.
[Novotny, Joseph M.; Kandula, Deepika] Univ Calif San Francisco, Global Hlth Grp, San Francisco, CA 94143 USA.
[Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Cohen, JM (reprint author), Clinton Hlth Access Initiat, Boston, MA USA.
EM jcohen@clintonhealthaccess.org
OI Cohen, Justin/0000-0003-4481-6784
FU Global Health Group at University of California, San Francisco; Bill and
Melinda Gates Foundation [1013170, 49446, 1032350]; Science and
Technology Directorate, Department of Homeland Security; Fogarty
International Center, National Institutes of Health; NIH/NIAID
[U19AI089674]
FX JMC, JN, and DK acknowledge funding support for this work from the
Global Health Group at University of California, San Francisco and the
Bill and Melinda Gates Foundation (#1013170). AJT acknowledges funding
support from the RAPIDD programme of the Science and Technology
Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health, and is also
supported by grants from NIH/NIAID (U19AI089674) and the Bill and
Melinda Gates Foundation (#49446 and #1032350).
NR 52
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U2 12
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD FEB 11
PY 2013
VL 12
AR 61
DI 10.1186/1475-2875-12-61
PG 12
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 137GF
UT WOS:000318422900001
PM 23398628
ER
PT J
AU Khandanpour, C
Phelan, JD
Vassen, L
Schutte, J
Chen, RY
Horman, SR
Gaudreau, MC
Krongold, J
Zhu, JF
Paul, WE
Duhrsen, U
Gottgens, B
Grimes, HL
Moroy, T
AF Khandanpour, Cyrus
Phelan, James D.
Vassen, Lothar
Schuette, Judith
Chen, Riyan
Horman, Shane R.
Gaudreau, Marie-Claude
Krongold, Joseph
Zhu, Jinfang
Paul, William E.
Duehrsen, Ulrich
Goettgens, Bertie
Grimes, H. Leighton
Moeroey, Tarik
TI Growth Factor Independence 1 Antagonizes a p53-Induced DNA Damage
Response Pathway in Lymphoblastic Leukemia
SO CANCER CELL
LA English
DT Article
ID ZINC-FINGER PROTEIN; T-CELL LYMPHOMAGENESIS; C-MYC; HUMAN NEUTROPENIA;
TRANSGENIC MICE; IN-VIVO; GFI-1; ACTIVATION; EXPRESSION; NOTCH1
AB Most patients with acute lymphoblastic leukemia (ALL) fail current treatments highlighting the need for better therapies. Because oncogenic signaling activates a p53-dependent DNA damage response and apoptosis, leukemic cells must devise appropriate countermeasures. We show here that growth factor independence 1 (Gfi1) can serve such a function because Gfi1 ablation exacerbates p53 responses and lowers the threshold for p53-induced cell death. Specifically, Gfi1 restricts p53 activity and expression of proapoptotic p53 targets such as Box, Noxa (Pmaip1), and Puma (Bbc3). Subsequently, Gfi1 ablation cures mice from leukemia and limits the expansion of primary human T-ALL xenografts in mice. This suggests that targeting Gfi1 could improve the prognosis of patients with T-ALL or other lymphoid leukemias.
C1 [Khandanpour, Cyrus; Vassen, Lothar; Chen, Riyan; Gaudreau, Marie-Claude; Krongold, Joseph; Moeroey, Tarik] Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada.
[Gaudreau, Marie-Claude; Moeroey, Tarik] Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada.
[Khandanpour, Cyrus] Univ Duisburg Essen, Univ Hosp, Dept Haematol, D-45122 Essen, Germany.
[Phelan, James D.; Horman, Shane R.; Grimes, H. Leighton] Cincinnati Childrens Hosp Med Ctr, Div Cellular & Mol Immunol, Cincinnati, OH 45229 USA.
[Grimes, H. Leighton] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol, Cincinnati, OH 45229 USA.
[Schuette, Judith; Goettgens, Bertie] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England.
[Schuette, Judith; Goettgens, Bertie] Univ Cambridge, Wellcome Trust, Cambridge Stem Cell Inst, MRC, Cambridge CB2 0XY, England.
[Krongold, Joseph; Moeroey, Tarik] McGill Univ, Div Expt Med, Montreal, PQ H3A 1A3, Canada.
[Zhu, Jinfang; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20829 USA.
RP Grimes, HL (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Cellular & Mol Immunol, Cincinnati, OH 45229 USA.
EM lee.grimes@cchmc.org; tarik.moroy@ircm.qc.ca
RI Zhu, Jinfang/B-7574-2012;
OI Krongold, Joseph/0000-0001-9100-7459; Gaudreau,
Marie-Claude/0000-0003-2833-7951; Gottgens,
Berthold/0000-0001-6302-5705; Grimes, H. Leighton/0000-0001-8162-6758
FU Cole Foundation; University Clinic of Essen; Max-Eder fellowship from
the German Cancer fund; University of Cincinnati Cancer Therapeutics T32
training grant [T32-CA117846]; Leukaemia and Lymphoma Research UK;
CancerFree Kids; Division of Intramural Research, National Institute of
Allergy and Infectious Diseases; Leukemia and Lymphoma Society of
America; NIH [CA105152, CA159845]; Center of Excellence in Molecular
Hematology [DK090971]; Canada Research Chair (Tier 1); Canadian
Institutes of Health Research (CIHR) [MOP-84238, MOP-111011]
FX We thank David Hildeman, Anil Jegga, Patrick Zweidler-McKay, Michelle
Kelliher, Tom Look, and Paul Jolicouer for expertise and for kindly
providing plasmids, cell lines, reagents, and mice. C.K. was supported
by a fellowship of the Cole Foundation, the IFZ fellowship of the
University Clinic of Essen, and a Max-Eder fellowship from the German
Cancer fund. J.D.P. is a Pelotonia Fellow and was supported by the
University of Cincinnati Cancer Therapeutics T32 training grant
(T32-CA117846). J.S. was supported by a Gordon Piller PhD studentship
from Leukaemia and Lymphoma Research UK, S.R.H. by a fellowship from
CancerFree Kids, and J.Z. and W.E.P. by the Division of Intramural
Research, National Institute of Allergy and Infectious Diseases. H.L.G.
was supported by the Leukemia and Lymphoma Society of America, NIH
CA105152, CA159845, Alex's Lemonade Stand, and thanks the Center of
Excellence in Molecular Hematology P30 award (DK090971). T.M. was
supported by a Canada Research Chair (Tier 1) and grants from the
Canadian Institutes of Health Research (CIHR, MOP-84238, MOP-111011).
C.K. and J.D.P. designed and performed experiments, analyzed data, and
wrote the manuscript. M.-C.G., L.V., J.S., R.C., S.R.H., J.K., and B.G.
performed experiments and assisted analyses. J.Z. and W.E.P. provided
the Gfi1f/f mouse strain. U.D. provided funding and oversaw
research. H.L.G. and T.M. were responsible for concept and design of
experiments, oversaw research, wrote the manuscript, and provided
funding.
NR 48
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U1 1
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD FEB 11
PY 2013
VL 23
IS 2
BP 200
EP 214
DI 10.1016/j.ccr.2013.01.011
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 091RO
UT WOS:000315067700010
PM 23410974
ER
PT J
AU Sourbier, C
Scroggins, BT
Ratnayake, R
Prince, TL
Lee, S
Lee, MJ
Nagy, PL
Lee, YH
Trepel, JB
Beutler, JA
Linehan, WM
Neckers, L
AF Sourbier, Carole
Scroggins, Bradley T.
Ratnayake, Ranjala
Prince, Thomas L.
Lee, Sunmin
Lee, Min-Jung
Nagy, Peter Literati
Lee, Young H.
Trepel, Jane B.
Beutler, John A.
Linehan, W. Marston
Neckers, Len
TI Englerin A Stimulates PKC theta to Inhibit Insulin Signaling and to
Simultaneously Activate HSF1: Pharmacologically Induced Synthetic
Lethality
SO CANCER CELL
LA English
DT Article
ID PROTEIN-KINASE-C; TRANSCRIPTION FACTOR HSF1; HEAT-SHOCK FACTOR-1;
CELL-LINE; HSP90 COMPLEX; CANCER; RESISTANCE; MODEL; PATHWAY; KIDNEY
AB The natural product englerin A (EA) binds to and activates protein kinase C-theta (PKC theta). EA-dependent activation of PKC theta induces an insulin-resistant phenotype, limiting the access of tumor cells to glucose. At the same time, EA causes PKC theta-mediated phosphorylation and activation of the transcription factor heat shock factor 1, an inducer of glucose dependence. By promoting glucose addiction, while simultaneously starving cells of glucose, EA proves to be synthetically lethal to highly glycolytic tumors.
C1 [Sourbier, Carole; Scroggins, Bradley T.; Prince, Thomas L.; Lee, Min-Jung; Linehan, W. Marston; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lee, Sunmin; Lee, Min-Jung; Trepel, Jane B.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ratnayake, Ranjala; Beutler, John A.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Nagy, Peter Literati] N Gene Res Labs Inc, H-1137 Budapest, Hungary.
RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM neckersl@mail.nih.gov
RI Beutler, John/B-1141-2009
OI Beutler, John/0000-0002-4646-1924
FU Intramural Research Program of the National Cancer Institute
FX We thank Drs. S. Calderwood (Harvard University, Cambridge, MA) and L.
Whitesell (Whitehead Institute, Cambridge, MA) for generously providing
reagents. We thank Dr. P.L. Nagy (N-Gene Research Laboratories,
Budapest, Hungary) for generously providing BGP-15. We thank Drs. N.
Kedei and P. Blumberg (National Cancer Institute, Bethesda, MD) and P.
Csermely (Semmelweis University, Budapest, Hungary) for helpful
discussions. This research was supported with funds provided by the
Intramural Research Program of the National Cancer Institute.
NR 41
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U2 28
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD FEB 11
PY 2013
VL 23
IS 2
BP 228
EP 237
DI 10.1016/j.ccr.2012.12.007
PG 10
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 091RO
UT WOS:000315067700012
PM 23352416
ER
PT J
AU Menon, MP
Hutchinson, L
Garver, J
Jaffe, ES
Woda, BA
AF Menon, Madhu P.
Hutchinson, Lloyd
Garver, Joanne
Jaffe, Elaine S.
Woda, Bruce A.
TI Transformation of Follicular Lymphoma to Epstein-Barr Virus-Related
Hodgkin-Like Lymphoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; STERNBERG-LIKE CELLS; CENTER B-CELL; CD30
EXPRESSION; DISEASE; ANTIGEN; TISSUE
C1 [Menon, Madhu P.; Jaffe, Elaine S.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hutchinson, Lloyd; Garver, Joanne; Woda, Bruce A.] Univ Massachusetts, Sch Med, Mem Med Ctr, Worcester, MA USA.
RP Menon, MP (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
OI Jaffe, Elaine/0000-0003-4632-0301
NR 26
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U1 0
U2 5
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 FEB 10
PY 2013
VL 31
IS 5
BP E53
EP E56
DI 10.1200/JCO.2012.43.2377
PG 4
WC Oncology
SC Oncology
GA 088FY
UT WOS:000314820400001
PM 23295788
ER
PT J
AU Szarama, KB
Gavara, N
Petralia, RS
Chadwick, RS
Kelley, MW
AF Szarama, Katherine B.
Gavara, Nuria
Petralia, Ronald S.
Chadwick, Richard S.
Kelley, Matthew W.
TI Thyroid hormone increases fibroblast growth factor receptor expression
and disrupts cell mechanics in the developing organ of corti
SO BMC DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Young's modulus; Hair cell; Pillar cell; Hypothyroid; Cell mechanics
ID AUDITORY SENSORY EPITHELIUM; ATOMIC-FORCE MICROSCOPY; DEVELOPING
INNER-EAR; ACTIN POLYMERIZATION; MOUSE COCHLEA; RAT COCHLEA; IN-VITRO;
F-ACTIN; TRANSCRIPTIONAL REGULATION; MICROTUBULE STABILITY
AB Background: Thyroid hormones regulate growth and development. However, the molecular mechanisms by which thyroid hormone regulates cell structural development are not fully understood. The mammalian cochlea is an intriguing system to examine these mechanisms, as cellular structure plays a key role in tissue development, and thyroid hormone is required for the maturation of the cochlea in the first postnatal week.
Results: In hypothyroid conditions, we found disruptions in sensory outer hair cell morphology and fewer microtubules in non-sensory supporting pillar cells. To test the functional consequences of these cytoskeletal defects on cell mechanics, we combined atomic force microscopy with live cell imaging. Hypothyroidism stiffened outer hair cells and supporting pillar cells, but pillar cells ultimately showed reduced cell stiffness, in part from a lack of microtubules. Analyses of changes in transcription and protein phosphorylation suggest that hypothyroidism prolonged expression of fibroblast growth factor receptors, and decreased phosphorylated Cofilin.
Conclusions: These findings demonstrate that thyroid hormones may be involved in coordinating the processes that regulate cytoskeletal dynamics and suggest that manipulating thyroid hormone sensitivity might provide insight into the relationship between cytoskeletal formation and developing cell mechanical properties.
C1 [Szarama, Katherine B.; Kelley, Matthew W.] NIDCD, Sect Dev Neurosci, Lab Cochlear Dev, NIH, Bethesda, MD USA.
[Szarama, Katherine B.; Gavara, Nuria; Chadwick, Richard S.] NIDCD, Sect Auditory Mech, Lab Cellular Biol, NIH, Bethesda, MD USA.
[Szarama, Katherine B.] Karolinska Inst, Ctr Hearing & Commun Res, Stockholm, Sweden.
[Szarama, Katherine B.] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
[Petralia, Ronald S.] NIDCD, Adv Imaging Core, NIH, Bethesda, MD USA.
RP Szarama, KB (reprint author), St Jude Childrens Res Hosp, Dept Biochem, Lab Joseph Opferman, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM Katherine.Szarama@stjude.org
FU National Institute on Deafness and Other Communication Disorders (NIDCD)
[DC000059, DC00003333]; NIH
FX We thank Ya-Xian Wang for help with tissue preparation for TEM, and S.
Raft, D.S. Sharlin, and A. Fridberger for comments on earlier versions
of this manuscript. This research was supported by the National
Institute on Deafness and Other Communication Disorders (NIDCD)
Intramural Research Program [DC000059 to M.W.K., DC00003333 to R.S.C.]
and in part with an Intramural Fellowship to Promote Diversity, from the
NIH Office of the Director to K.B.S.
NR 103
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U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-213X
J9 BMC DEV BIOL
JI BMC Dev. Biol.
PD FEB 9
PY 2013
VL 13
AR 6
DI 10.1186/1471-213X-13-6
PG 18
WC Developmental Biology
SC Developmental Biology
GA 101KJ
UT WOS:000315773600001
PM 23394545
ER
PT J
AU Tana, MM
Hoofnagle, JH
AF Tana, Michele M.
Hoofnagle, Jay H.
TI Scar undone: long-term therapy of hepatitis B
SO LANCET
LA English
DT Editorial Material
ID INTERFERON-ALPHA THERAPY; LAMIVUDINE; IMPROVEMENT; ENTECAVIR; ADEFOVIR
C1 [Tana, Michele M.; Hoofnagle, Jay H.] NIDDKD, Liver Dis Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Hoofnagle, JH (reprint author), NIDDKD, Liver Dis Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
EM hoofnaglej@extra.niddk.nih.gov
NR 16
TC 3
Z9 3
U1 0
U2 5
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 FEB 9
PY 2013
VL 381
IS 9865
BP 433
EP 434
DI 10.1016/S0140-6736(12)61721-8
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 088CH
UT WOS:000314810900010
PM 23234726
ER
PT J
AU Pyo, CW
Wang, RH
Vu, QY
Cereb, N
Yang, SY
Duh, FM
Wolinsky, S
Martin, MP
Carrington, M
Geraghty, DE
AF Pyo, Chul-Woo
Wang, Ruihan
Vu, Quyen
Cereb, Nezih
Yang, Soo Young
Duh, Fuh-Mei
Wolinsky, Steven
Martin, Maureen P.
Carrington, Mary
Geraghty, Daniel E.
TI Recombinant structures expand and contract inter and intragenic
diversification at the KIR locus
SO BMC GENOMICS
LA English
DT Article
DE Natural killer cells; Human; KIR; Recombinant structures
ID IMMUNOGLOBULIN-LIKE RECEPTOR; KILLER-CELL RECEPTOR; CLASS-I MOLECULES;
COPY NUMBER VARIATION; HLA-G; ALLELIC POLYMORPHISM; INHIBITORY
RECEPTORS; ADAPTIVE IMMUNITY; VIRUS-INFECTION; HUMAN-DISEASE
AB Background: The human KIR genes are arranged in at least six major gene-content haplotypes, all of which are combinations of four centromeric and two telomeric motifs. Several less frequent or minor haplotypes also exist, including insertions, deletions, and hybridization of KIR genes derived from the major haplotypes. These haplotype structures and their concomitant linkage disequilibrium among KIR genes suggest that more meaningful correlative data from studies of KIR genetics and complex disease may be achieved by measuring haplotypes of the KIR region in total.
Results: Towards that end, we developed a KIR haplotyping method that reports unambiguous combinations of KIR gene-content haplotypes, including both phase and copy number for each KIR. A total of 37 different gene content haplotypes were detected from 4,512 individuals and new sequence data was derived from haplotypes where the detailed structure was not previously available.
Conclusions: These new structures suggest a number of specific recombinant events during the course of KIR evolution, and add to an expanding diversity of potential new KIR haplotypes derived from gene duplication, deletion, and hybridization.
C1 [Pyo, Chul-Woo; Wang, Ruihan; Vu, Quyen; Geraghty, Daniel E.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Cereb, Nezih; Yang, Soo Young] Histogenetics LLC, Ossining, NY USA.
[Duh, Fuh-Mei; Martin, Maureen P.; Carrington, Mary] Frederick Natl Lab Canc Res, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA.
[Martin, Maureen P.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA.
RP Geraghty, DE (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA.
EM geraghty@fhcrc.org
OI Wolinsky, Steven/0000-0002-9625-6697
FU National Institutes of Health [RR018669]
FX This work was supported by the National Institutes of Health [RR018669
to D.E.G.]. The expert contributions of Dr. Shu Shen in the preparation
of the manuscript are gratefully acknowledged. We thank the organizers
of the UCLA International Cell Exchange for the KIR reference panel
(www.hla.ucla.edu/cellDna.htm).
NR 61
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U2 8
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 FEB 8
PY 2013
VL 14
AR 89
DI 10.1186/1471-2164-14-89
PG 17
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 110VV
UT WOS:000316476200001
PM 23394822
ER
PT J
AU Pan, HQ
Ardini, MA
Bakalov, V
DeLatte, M
Eggers, P
Ganapathi, L
Hollingsworth, CR
Levy, J
Li, SP
Pratt, J
Pugh, N
Qin, Y
Rasooly, R
Ray, H
Richardson, JE
Riley, AF
Rogers, SM
Tan, S
Turner, CF
White, S
Cooley, PC
AF Pan, Huaqin
Ardini, Mary-Anne
Bakalov, Vesselina
DeLatte, Michael
Eggers, Paul
Ganapathi, Laxminarayana
Hollingsworth, Craig R.
Levy, Joshua
Li, Sheping
Pratt, Joseph
Pugh, Norma
Qin, Ying
Rasooly, Rebekah
Ray, Helen
Richardson, Jean E.
Riley, Amanda Flynn
Rogers, Susan M.
Tan, Sylvia
Turner, Charles F.
White, Stacie
Cooley, Philip C.
TI 'What's in the NIDDK CDR?'-public query tools for the NIDDK central data
repository
SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
LA English
DT Article
AB The National Institute of Diabetes and Digestive Disease (NIDDK) Central Data Repository (CDR) is a web-enabled resource available to researchers and the general public. The CDR warehouses clinical data and study documentation from NIDDK funded research, including such landmark studies as The Diabetes Control and Complications Trial (DCCT, 1983-93) and the Epidemiology of Diabetes Interventions and Complications (EDIC, 1994-present) follow-up study which has been ongoing for more than 20 years. The CDR also houses data from over 7 million biospecimens representing 2 million subjects. To help users explore the vast amount of data stored in the NIDDK CDR, we developed a suite of search mechanisms called the public query tools (PQTs). Five individual tools are available to search data from multiple perspectives: study search, basic search, ontology search, variable summary and sample by condition. PQT enables users to search for information across studies. Users can search for data such as number of subjects, types of biospecimens and disease outcome variables without prior knowledge of the individual studies. This suite of tools will increase the use and maximize the value of the NIDDK data and biospecimen repositories as important resources for the research community. Database URL:https://www.niddkrepository.org/niddk/home.do
C1 [Pan, Huaqin; Ardini, Mary-Anne; Bakalov, Vesselina; DeLatte, Michael; Ganapathi, Laxminarayana; Hollingsworth, Craig R.; Levy, Joshua; Li, Sheping; Pratt, Joseph; Pugh, Norma; Qin, Ying; Ray, Helen; Richardson, Jean E.; Riley, Amanda Flynn; Rogers, Susan M.; Tan, Sylvia; Turner, Charles F.; White, Stacie; Cooley, Philip C.] RTI Int Social Stat & Environm Sci, Res Triangle Pk, NC 27709 USA.
[Eggers, Paul; Rasooly, Rebekah] NIDDK, Div Kidney Urol & Hematol Dis, Bethesda, MD 20892 USA.
[Turner, Charles F.] CUNY Queens Coll, Flushing, NY 11367 USA.
[Turner, Charles F.] CUNY Grad Ctr, Flushing, NY 11367 USA.
RP Cooley, PC (reprint author), RTI Int Social Stat & Environm Sci, POB 12194, Res Triangle Pk, NC 27709 USA.
EM pcc@rtii.org
OI Qin, Ying/0000-0002-6099-2190; Rasooly, Rebekah/0000-0002-6357-5528
FU [HHSN267200800016C]
FX National Institute of Diabetes and Digestive and Kidney Diseases;
National Institutes of Health, NIH American Recovery and Reinvestment
Act (ARRA) of 2009, Department of Health and Human Services, under
Contracts (HHSN: 267200800015C, 267200800016C and 267200800018C).
Funding for open access charge: HHSN267200800016C.
NR 5
TC 2
Z9 2
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1758-0463
J9 DATABASE-OXFORD
JI Database
PD FEB 8
PY 2013
AR bas058
DI 10.1093/database/bas058
PG 11
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA 106XZ
UT WOS:000316180000001
ER
PT J
AU Liu, ZG
Yedidi, RS
Wang, Y
Dewdney, TG
Reiter, SJ
Brunzelle, JS
Kovari, IA
Kovari, LC
AF Liu, Zhigang
Yedidi, Ravikiran S.
Wang, Yong
Dewdney, Tamaria G.
Reiter, Samuel J.
Brunzelle, Joseph S.
Kovari, Iulia A.
Kovari, Ladislau C.
TI Insights into the mechanism of drug resistance: X-ray structure analysis
of multi-drug resistant HIV-1 protease ritonavir complex
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE HIV-1 protease; Multi-drug resistance; X-ray crystallography; IC50;
Ritonavir
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE-SITE; INHIBITOR; REFINEMENT;
MUTATIONS; VARIANTS; THERAPY; ABT-538; MODEL
AB Ritonavir (RTV) is a first generation HIV-1 protease inhibitor with rapidly emerging drug resistance. Mutations at residues 46, 54, 82 and 84 render the HIV-1 protease drug resistant against RTV. We report the crystal structure of multi-drug resistant (MDR) 769 HIV-1 protease (carrying resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84 and 90) complexed with RTV and the in vitro enzymatic IC50 of RTV against MDR HIV-1 protease. The structural and functional studies demonstrate significant drug resistance of MDR HIV-1 protease against RTV, arising from reduced hydrogen bonds and Van der Waals interactions between RTV and MDR HIV-1 protease. (C) 2013 Published by Elsevier Inc.
C1 [Liu, Zhigang; Yedidi, Ravikiran S.; Wang, Yong; Dewdney, Tamaria G.; Reiter, Samuel J.; Kovari, Iulia A.; Kovari, Ladislau C.] Wayne State Univ, Dept Biochem & Mol Biol, Sch Med, Detroit, MI 48201 USA.
[Liu, Zhigang] Harbor Hosp Baltimore, Div Internal Med, Baltimore, MD 21225 USA.
[Yedidi, Ravikiran S.] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
[Brunzelle, Joseph S.] Northwestern Univ, Feinberg Sch Med, Life Sci Collaborat Access Team, Chicago, IL 60611 USA.
[Brunzelle, Joseph S.] Northwestern Univ, Feinberg Sch Med, Dept Mol Pharmacol & Biol Chem, Chicago, IL 60611 USA.
RP Kovari, LC (reprint author), 540 E Canfield Ave,4263 Scott Hall, Detroit, MI 48201 USA.
EM kovari@med.wayne.edu
RI Liu, Zhigang/A-2003-2014;
OI Yedidi, Ravikiran/0000-0003-2755-1307
FU National Institutes of Health [AI65294]; American Foundation for AIDS
Research [106457-34-RGGN]
FX This research was supported by the National Institutes of Health Grant
AI65294 and a Grant from the American Foundation for AIDS Research
(106457-34-RGGN).
NR 26
TC 2
Z9 2
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD FEB 8
PY 2013
VL 431
IS 2
BP 232
EP 238
DI 10.1016/j.bbrc.2012.12.127
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 095HM
UT WOS:000315325300021
PM 23313846
ER
PT J
AU Hong, JJ
Feng, HQ
Zhou, Z
Ghirlando, R
Bai, YW
AF Hong, Jingjun
Feng, Hanqiao
Zhou, Zheng
Ghirlando, Rodolfo
Bai, Yawen
TI Identification of Functionally Conserved Regions in the Structure of the
Chaperone/CenH3/H4 Complex
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE NMR; Cse4; CENP-A; centromere; histone
ID CENTROMERE-SPECIFIC NUCLEOSOMES; E3 UBIQUITIN LIGASE; FISSION YEAST
SCM3; HISTONE H3 VARIANT; CENP-A; ANALYTICAL ULTRACENTRIFUGATION;
SEDIMENTATION-VELOCITY; BUDDING YEAST; HJURP; CHROMATIN
AB In eukaryotes, a variant of conventional histone H3 termed CenH3 epigenetically marks the centromere. The conserved CenH3 chaperone specifically recognizes CenH3 and is required for CenH3 deposition at the centromere. Recently, the structures of the chaperone/CenH3/H4 complexes have been determined for Homo sapiens (Hs) and the budding yeasts Saccharomyces cerevisiae (Sc) and Kluyveromyces lactis (KI). Surprisingly, the three structures are very different, leading to different proposed structural bases for chaperone function. The question of which structural region of CenH3 provides the specificity determinant for the chaperone recognition is not fully answered. Here, we investigated these issues using solution NMR and site-directed mutagenesis. We discovered that, in contrast to previous findings, the structures of the KI and Sc chaperone/CenH3/H4 complexes are actually very similar. This new finding reveals that both budding yeast and human chaperones use a similar structural region to block DNA from binding to the histones. Our mutational analyses further indicate that the N-terminal region of the CenH3 alpha 2 helix is sufficient for specific recognition by the chaperone for both budding yeast and human. Thus, our studies have identified conserved structural bases of how the chaperones recognize CenH3 and perform the chaperone function. Published by Elsevier Ltd.
C1 [Hong, Jingjun; Feng, Hanqiao; Bai, Yawen] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Zhou, Zheng] Chinese Acad Sci, Natl Lab Biomacromol, Inst Biophys, Beijing 100101, Peoples R China.
[Ghirlando, Rodolfo] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Bai, YW (reprint author), NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM yawen@helix.nih.gov
OI 周, 政/0000-0002-1423-7231
FU National Cancer. Institute; National Institute of Diabetes and Digestive
and Kidney Diseases
FX We thank Mr. Shipeng Li for purification of proteins and Dr. Jemima
Barrowman for editing the manuscript. This research was supported by the
Intramural Research Programs of the National Cancer. Institute and the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 31
TC 6
Z9 6
U1 0
U2 9
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD FEB 8
PY 2013
VL 425
IS 3
BP 536
EP 545
DI 10.1016/j.jmb.2012.11.021
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 095BG
UT WOS:000315308900008
PM 23178171
ER
PT J
AU Jiang, CT
Kim, JH
Li, F
Qu, AJ
Gavrilova, O
Shah, YM
Gonzalez, FJ
AF Jiang, Changtao
Kim, Jung-Hwan
Li, Fei
Qu, Aijuan
Gavrilova, Oksana
Shah, Yatrik M.
Gonzalez, Frank J.
TI Hypoxia-inducible Factor 1 alpha Regulates a SOCS3-STAT3-Adiponectin
Signal Transduction Pathway in Adipocytes
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INSULIN-RESISTANCE; ADIPOSE-TISSUE; GENE-EXPRESSION; DSBA-L; METABOLIC
SYNDROME; OBESITY; ADIPONECTIN; MICE; SECRETION; CELLS
AB Obesity has been identified as a major risk factor for type 2 diabetes, characterized by insulin resistance in insulin target tissues. Hypoxia-inducible factor 1 alpha (HIF1 alpha) regulates pathways in energy metabolism that become dysregulated in obesity. Earlier studies revealed that HIF1 alpha in adipose tissue is markedly elevated in high-fat diet-fed mice that are obese and insulin-resistant. Genetic ablation of HIF1 alpha in adipose tissue decreased insulin resistance and obesity, accompanied by increased serum adiponectin levels. However, the exact mechanism whereby HIF1 alpha regulates adiponectin remains unclear. Here, acriflavine (ACF), an inhibitor of HIF1 alpha, induced the expression of adiponectin and reduced the expression of SOCS3 in cultured 3T3-L1 adipocytes. Mechanistic studies revealed that HIF1 alpha suppressed the expression of adiponectin through a SOCS3-STAT3 pathway. Socs3 was identified as a novel HIF1 alpha target gene based on chromatin immunoprecipitation and luciferase assays. STAT3 directly regulated adiponectin in vitro in cultured 3T3-L1 adipocytes. ACF was found to prevent diet-induced obesity and insulin resistance. In vivo, ACF also regulated the SOCS3-STAT3-adiponectin pathway, and inhibition of HIF1 alpha in adipose tissue was essential for ACF to improve the SOCS3-STAT3-adiponectin pathway to counteract insulin resistance. This study provides evidence for a novel target gene and signal transduction pathway in adipocytes and indicates that inhibitors of HIF1 alpha have potential utility for the treatment of obesity and type 2 diabetes.
C1 [Jiang, Changtao; Kim, Jung-Hwan; Li, Fei; Qu, Aijuan; Shah, Yatrik M.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Gavrilova, Oksana] NIDDK, Mouse Metab Core Lab, NIH, Bethesda, MD 20892 USA.
[Shah, Yatrik M.] Univ Michigan, Div Gastroenterol, Sch Med, Dept Mol & Integrat Physiol & Internal Med, Ann Arbor, MI 48109 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
RI Li, Fei/F-6849-2013
FU NCI; NIDDK; National Institutes of Health [CA148828]
FX This work was supported, in whole or in part, by the NCI and NIDDK
Intramural Research Programs and National Institutes of Health Grant
CA148828 (to Y. M. S.).
NR 52
TC 15
Z9 18
U1 0
U2 18
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 FEB 8
PY 2013
VL 288
IS 6
BP 3844
EP 3857
DI 10.1074/jbc.M112.426338
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 088OP
UT WOS:000314845000016
PM 23255598
ER
PT J
AU Henderson, MJ
Richie, CT
Airavaara, M
Wang, Y
Harvey, BK
AF Henderson, Mark J.
Richie, Christopher T.
Airavaara, Mikko
Wang, Yun
Harvey, Brandon K.
TI Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) Secretion and
Cell Surface Binding Are Modulated by KDEL Receptors
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID RETICULUM STRESS-RESPONSE; ISCHEMIC BRAIN-INJURY; DOPAMINERGIC-NEURONS;
BREFELDIN-A; IN-VITRO; PROTEIN; EXPRESSION; ER; HEART; GOLGI
AB Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) stress-responsive protein with neuroprotective effects in animal models of neuro-degeneration, but the underlying mechanism is not understood. We constructed a set of lentiviral vectors that contain or lack the highly conserved final four amino acids of MANF ("RTDL"), which resemble the canonical ER retention signal ("KDEL"), to study MANF regulation in neuroblastoma cells and rat primary cortical neurons. The RTDL sequence was required for both ER retention and secretory response to ER stress. Overexpression of KDEL receptor paralogs (KDELRs) differentially reduced MANF secretion but had no effect on MANF lacking RTDL. MANF binding to the plasma membrane also required the RTDL sequence and was inhibited with a peptide known to interact with KDELRs, suggesting MANF binds KDELRs at the surface. We detected surface localization of FLAG-tagged KDELRs, with levels increasing following ER stress. Our study provides new insight into the regulation of MANF trafficking and has implications for other secreted proteins containing a KDEL-like retention signal.
C1 [Henderson, Mark J.; Richie, Christopher T.; Airavaara, Mikko; Wang, Yun; Harvey, Brandon K.] NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
[Airavaara, Mikko] Univ Helsinki, Inst Biotechnol, Helsinki 00014, Finland.
[Wang, Yun] Natl Hlth Res Inst, Ctr Neuropsychiat Res, Zhunan, Taiwan.
RP Harvey, BK (reprint author), NIDA, Intramural Res Program, Ste 200,Rm 06A729,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM BHarvey@intra.nida.nih.gov
OI Airavaara, Mikko/0000-0002-2026-1609
FU National Institutes of Health Intramural Research Program, National
Institute on Drug Abuse
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Research Program, National Institute on Drug Abuse.
NR 40
TC 23
Z9 23
U1 1
U2 23
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 FEB 8
PY 2013
VL 288
IS 6
BP 4209
EP 4225
DI 10.1074/jbc.M112.400648
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 088OP
UT WOS:000314845000048
PM 23255601
ER
PT J
AU Mollan, TL
Banerjee, S
Wu, G
Siburt, CJP
Tsai, AL
Olson, JS
Weiss, MJ
Crumbliss, AL
Alayash, AI
AF Mollan, Todd L.
Banerjee, Sambuddha
Wu, Gang
Siburt, Claire J. Parker
Tsai, Ah-Lim
Olson, John S.
Weiss, Mitchell J.
Crumbliss, Alvin L.
Alayash, Abdu I.
TI alpha-Hemoglobin Stabilizing Protein (AHSP) Markedly Decreases the Redox
Potential and Reactivity of alpha-Subunits of Human HbA with Hydrogen
Peroxide
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BETA-THALASSEMIA; IN-VIVO; MOLECULAR-MECHANISM; HUMAN OXYHEMOGLOBIN;
GLOBIN BINDING; GUINEA-PIGS; CHAINS; OXIDATION; HEME; MYOGLOBIN
AB alpha-Hemoglobin stabilizing protein (AHSP) is a molecular chaperone that binds monomeric alpha-subunits of human hemoglobin A (HbA) and modulates heme iron oxidation and subunit folding states. Although AHSP center dot alpha Hb complexes autoxidize more rapidly than HbA, the redox mechanisms appear to be similar. Both metHbA and isolated met-beta-subunits undergo further oxidation in the presence of hydrogen peroxide (H2O2) to form ferryl heme species. Surprisingly, much lower levels of H2O2-induced ferryl heme are produced by free met-alpha-subunits as compared with met-beta-subunits, and no ferryl heme is detected in H2O2-treated AHSP center dot met-alpha-complex at pH values from 5.0 to 9.0 at 23 degrees C. Ferryl heme species were similarly not detected in AHSP center dot met-alpha Pro-30 mutants known to exhibit different rates of autoxidation and hemin loss. EPR data suggest that protein-based radicals associated with the ferryl oxidation state exist within HbA alpha- and beta-subunits. In contrast, treatment of free alpha-subunits with H2O2 yields much smaller radical signals, and no radicals are detected when H2O2 is added to AHSP center dot alpha-complexes. AHSP binding also dramatically reduces the redox potential of alpha-subunits, from +40 to -78 mV in 1 M glycine buffer, pH 6.0, at 8 degrees C, demonstrating independently that AHSP has a much higher affinity for Fe(III) versus Fe(II) alpha-subunits. Hexacoordination in the AHSP center dot met-alpha complex markedly decreases the rate of the initial H2O2 reaction with iron and thus provides alpha-subunits protection against damaging oxidative reactions.
C1 [Mollan, Todd L.; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20852 USA.
[Banerjee, Sambuddha; Siburt, Claire J. Parker; Crumbliss, Alvin L.] Duke Univ, Dept Chem, Durham, NC 27708 USA.
[Wu, Gang; Tsai, Ah-Lim] Univ Texas Houston, Sch Med, Dept Internal Med, Div Hematol, Houston, TX 77030 USA.
[Olson, John S.] Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77251 USA.
[Weiss, Mitchell J.] Univ Penn, Cell & Mol Biol Grp, Philadelphia, PA 19104 USA.
RP Alayash, AI (reprint author), US FDA, CBER, NIH, 8800 Rockville Pike,Bldg 29,Rm 112, Bethesda, MD 20852 USA.
EM abdu.alayash@fda.hhs.gov
FU National Institutes of Health [HL110900, HL095821, HL47020, GM35649,
DK61692, HL087427, GM008362]; Welch Grant [C-0612]; National Science
Foundation [CHE 0809466]; United States Food and Drug Administration
[MODSCI 2011]; Duke University
FX This work was supported, in whole or in part, by National Institutes of
Health Grants HL110900 (to A. I. A.), HL095821 (to A.-L. T.), HL47020
(to J. S. O.), HL110900 (to J. S. O.), GM35649 (to J. S. O.), DK61692
(to M. J. W.), HL087427 (to M. J. W.), and GM008362 (to T. L. M.), Welch
Grant C-0612 (to J. S. O.), National Science Foundation Grant CHE
0809466 (to A. L. C.), and the United States Food and Drug
Administration (MODSCI 2011) (to A. I. A.).; Supported by a grant from
Duke University.
NR 58
TC 11
Z9 11
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 FEB 8
PY 2013
VL 288
IS 6
BP 4288
EP 4298
DI 10.1074/jbc.M112.412064
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 088OP
UT WOS:000314845000057
PM 23264625
ER
PT J
AU Amaral, J
Lee, JW
Chou, J
Campos, MM
Rodriguez, IR
AF Amaral, Juan
Lee, Jung Wha
Chou, Joshua
Campos, Maria M.
Rodriguez, Ignacio R.
TI 7-Ketocholesterol Induces Inflammation and Angiogenesis In Vivo: A Novel
Rat Model
SO PLOS ONE
LA English
DT Article
ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; LOW-DENSITY-LIPOPROTEIN;
MACULAR DEGENERATION; CELLS; OXYSTEROLS; VEGF; CHOLESTEROL; MACROPHAGES;
OXIDATION; MEMBRANE
AB Accumulation of 7-Ketocholesterol (7KCh) in lipid deposits has been implicated in a variety of chronic diseases including atherosclerosis, Alzheimer's disease and age-related macular degeneration. 7KCh is known to be pro-inflammatory and cytotoxic to various types of cultured cells but little is known about its effects in vivo. In this study we have investigated the effects of 7KCh in vivo by implanting biodegradable wafers into the anterior chamber of the rat eye. The wafers were prepared using a mixture of two biodegradable polymers with different amounts of 7KCh. The 7KCh-containing implants induced massive angiogenesis and inflammation. By contrast, no angiogenesis and very little inflammation were observed with cholesterol-containing implants. The neovessel growth was monitored by fluorescein angiography. Neovessels were observed 4 days post implantation and peaked between 7 to 10 days. The angiography and isolectin IB4 labeling demonstrated that the neovessels originated from the limbus and grew through the cornea. Immunolabeling with anti-CD68 suggested that the 7KCh-containing implants had extensive macrophage infiltration as well as other cell types. A significant increase in VEGF was also observed in 7KCh-containing implants by fluorescent immunolabeling and by immunoblot of the aqueous humor (AH). Direct measurement of VEGF, IL-1 beta and GRO/KC demonstrated a marked elevation of these factors in the AH of the 7KCh-implants. In summary this study demonstrates two important things: 1) 7KCh is pro-angiogenic and pro-inflammatory in vivo and 2) implants containing 7KCh may be used to create a novel angiogenesis model in rats.
C1 [Amaral, Juan; Lee, Jung Wha; Chou, Joshua; Rodriguez, Ignacio R.] NEI, Mech Retinal Dis Sect, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Campos, Maria M.] NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA.
RP Rodriguez, IR (reprint author), NEI, Mech Retinal Dis Sect, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM rodriguezi@nei.nih.gov
FU National Eye Institute
FX National Eye Institute intramural research program (IRR). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 25
TC 16
Z9 16
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 FEB 8
PY 2013
VL 8
IS 2
AR e56099
DI 10.1371/journal.pone.0056099
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 086CJ
UT WOS:000314660300058
PM 23409131
ER
PT J
AU Mukherjee, R
Evans, P
Singh, LN
Hannenhalli, S
AF Mukherjee, Rithun
Evans, Perry
Singh, Larry N.
Hannenhalli, Sridhar
TI Correlated Evolution of Positions within Mammalian cis Elements
SO PLOS ONE
LA English
DT Article
ID TRANSCRIPTION FACTOR-BINDING; COMPENSATORY EVOLUTION;
MAXIMUM-LIKELIHOOD; RESPONSE ELEMENTS; DNA; SITES; SEQUENCE; GENE;
CONSERVATION; SPECIFICITY
AB Transcriptional regulation critically depends on proper interactions between transcription factors (TF) and their cognate DNA binding sites. The widely used model of TF-DNA binding - the Positional Weight Matrix (PWM) - presumes independence between positions within the binding site. However, there is evidence to show that the independence assumption may not always hold, and the extent of interposition dependence is not completely known. We hypothesize that the interposition dependence should partly be manifested as correlated evolution at the positions. We report a Maximum-Likelihood (ML) approach to infer correlated evolution at any two positions within a PWM, based on a multiple alignment of 5 mammalian genomes. Application to a genome-wide set of putative cis elements in human promoters reveals a prevalence of correlated evolution within cis elements. We found that the interdependence between two positions decreases with increasing distance between the positions. The interdependent positions tend to be evolutionarily more constrained and moreover, the dependence patterns are relatively similar across structurally related transcription factors. Although some of the detected mutational dependencies may be due to context-dependent genomic hyper-mutation, notably CG to TG, the majority is likely due to context-dependent preferences for specific nucleotide combinations within the cis elements. Patterns of evolution at individual nucleotide positions within mammalian TF binding sites are often significantly correlated, suggesting interposition dependence. The proposed methodology is also applicable to other classes of non-coding functional elements. A detailed investigation of mutational dependencies within specific motifs could reveal preferred nucleotide combinations that may help refine the DNA binding models.
C1 [Mukherjee, Rithun] Fred Hutchinson Canc Res Ctr, Computat Biol Program, Seattle, WA 98104 USA.
[Evans, Perry] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA.
[Singh, Larry N.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Hannenhalli, Sridhar] Univ Maryland, Dept Cell & Mol Biol, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
RP Mukherjee, R (reprint author), Fred Hutchinson Canc Res Ctr, Computat Biol Program, 1124 Columbia St, Seattle, WA 98104 USA.
EM rmukherj@fhcrc.org; sridhar@umiacs.umd.edu
FU NIH [GM085226]
FX Source of funding: The work was supported by NIH GM085226 to SH. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 34
TC 2
Z9 2
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 8
PY 2013
VL 8
IS 2
AR e55521
DI 10.1371/journal.pone.0055521
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 086CJ
UT WOS:000314660300020
PM 23408994
ER
PT J
AU Di Virgilio, M
Callen, E
Yamane, A
Zhang, WZ
Jankovic, M
Gitlin, AD
Feldhahn, N
Resch, W
Oliveira, TY
Chait, BT
Nussenzweig, A
Casellas, R
Robbiani, DF
Nussenzweig, MC
AF Di Virgilio, Michela
Callen, Elsa
Yamane, Arito
Zhang, Wenzhu
Jankovic, Mila
Gitlin, Alexander D.
Feldhahn, Niklas
Resch, Wolfgang
Oliveira, Thiago Y.
Chait, Brian T.
Nussenzweig, Andre
Casellas, Rafael
Robbiani, Davide F.
Nussenzweig, Michel C.
TI Rif1 Prevents Resection of DNA Breaks and Promotes Immunoglobulin Class
Switching
SO SCIENCE
LA English
DT Article
ID B-LYMPHOCYTES; END RESECTION; 53BP1; RECOMBINATION; REPLICATION; REPAIR;
DAMAGE; AID; REGULATOR; TELOMERES
AB DNA double-strand breaks (DSBs) represent a threat to the genome because they can lead to the loss of genetic information and chromosome rearrangements. The DNA repair protein p53 binding protein 1 (53BP1) protects the genome by limiting nucleolytic processing of DSBs by a mechanism that requires its phosphorylation, but whether 53BP1 does so directly is not known. Here, we identify Rap1-interacting factor 1 (Rif1) as an ATM (ataxia-telangiectasia mutated) phosphorylation-dependent interactor of 53BP1 and show that absence of Rif1 results in 5'-3' DNA-end resection in mice. Consistent with enhanced DNA resection, Rif1 deficiency impairs DNA repair in the G(1) and S phases of the cell cycle, interferes with class switch recombination in B lymphocytes, and leads to accumulation of chromosome DSBs.
C1 [Di Virgilio, Michela; Jankovic, Mila; Gitlin, Alexander D.; Feldhahn, Niklas; Oliveira, Thiago Y.; Robbiani, Davide F.; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
[Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst HHMI, New York, NY 10065 USA.
[Callen, Elsa; Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
[Callen, Elsa; Nussenzweig, Andre] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Yamane, Arito; Resch, Wolfgang; Casellas, Rafael] NCI, Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bethesda, MD 20892 USA.
[Zhang, Wenzhu; Chait, Brian T.] Rockefeller Univ, Lab Mass Spectrometry & Gaseous Ion Chem, New York, NY 10065 USA.
[Oliveira, Thiago Y.] Univ Sao Paulo, Fac Med, Dept Genet, BR-14049 Ribeirao Preto, Brazil.
[Oliveira, Thiago Y.] Natl Inst Sci & Technol Stem Cells & Cell Therapy, BR-14049 Ribeirao Preto, Brazil.
RP Nussenzweig, MC (reprint author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
EM nussen@rockefeller.edu
RI Yamane, Arito/A-2959-2013;
OI Oliveira, Thiago/0000-0002-2654-0879
FU NIH [GM007739, AI037526, RR022220, RR00862, GM103314]; NIAMS at the NIH;
NCI at the NIH; Center for Cancer Research
FX We thank all members of the Nussenzweig laboratory for discussion, D.
Bosque and T. Eisenreich for help in managing mouse colonies, A.
Gazumyan for assistance with Igh germline and AID transcript levels
analysis, and K. Yao for help with genotyping. We thank T. de Lange (The
Rockefeller University, New York) for Rif1F/F mice; S.
Buonomo (European Molecular Biology Laboratory Mouse Biology Unit,
Monterotondo, Italy) for the anti-mouse Rif1 serum #1240; G. Gutierrez
(NIAMS, NIH, Bethesda, MD) for Illumina sequencing; N. Zampieri
(Columbia University, New York) for assistance with immunofluorescence
image processing, and M. P. Rout, J. LaCava, S. Obado, and L. Hough (The
Rockefeller University) for invaluable help, discussions, and protocols
for cryolysis and magnetic bead-mediated immunoisolation. The data
presented in the manuscript are tabulated in the main text and in the
supplementary materials. Sequence data shown in Fig. 4 have been
deposited in the Gene Expression Omnibus database (accession number
GSE42298) at www.ncbi.nlm.nih.gov/geo/. M. D. V. was a Fellow of the
American Italian Cancer Foundation, and A. D. G. was supported by NIH
Medical Scientist Training Program grant GM007739. This work was
supported in part by NIH grants AI037526 (M. C. N.), RR022220 (B. T.
C.), RR00862 (B. T. C.), and GM103314 (B. T. C.); and by the intramural
program of NIAMS at the NIH (R. C.); and the intramural research program
of NCI at the NIH and Center for Cancer Research (A. N. and E. C.). M.
C. N. is an HHMI Investigator.
NR 26
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U1 0
U2 15
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 FEB 8
PY 2013
VL 339
IS 6120
BP 711
EP 715
DI 10.1126/science.1230624
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 085BM
UT WOS:000314585600047
PM 23306439
ER
PT J
AU Hu, GQ
Cui, KR
Northrup, D
Liu, CY
Wang, CC
Tang, QS
Ge, K
Levens, D
Crane-Robinson, C
Zhao, KJ
AF Hu, Gangqing
Cui, Kairong
Northrup, Daniel
Liu, Chengyu
Wang, Chaochen
Tang, Qingsong
Ge, Kai
Levens, David
Crane-Robinson, Colyn
Zhao, Keji
TI H2A.Z Facilitates Access of Active and Repressive Complexes to Chromatin
in Embryonic Stem Cell Self-Renewal and Differentiation
SO CELL STEM CELL
LA English
DT Article
ID HISTONE VARIANT H2A.Z; HUMAN GENOME; DNA METHYLATION; METHYLTRANSFERASE
ACTIVITY; REGULATORY SEQUENCES; ES CELLS; ENHANCERS; ACETYLATION;
PROMOTERS; GENES
AB Chromatin modifications have been implicated in the self-renewal and differentiation of embryonic stem cells (ESCs). However, the function of histone variant H2A.Z in ESCs remains unclear. We show that H2A.Z is highly enriched at promoters and enhancers and is required for both efficient self-renewal and differentiation of murine ESCs. H2A.Z deposition leads to an abnormal nucleosome structure, decreased nucleosome occupancy, and increased chromatin accessibility. In self-renewing ESCs, knockdown of H2A.Z compromises OCT4 binding to its target genes and leads to decreased binding of MLL complexes to active genes and of PRC2 complex to repressed genes. During differentiation of ESCs, inhibition of H2A.Z also compromises RA-induced RAR alpha binding, activation of differentiation markers, and the repression of pluripotency genes. We propose that H2A.Z mediates such contrasting activities by acting as a general facilitator that generates access for a variety of complexes, both activating and repressive.
C1 [Hu, Gangqing; Cui, Kairong; Northrup, Daniel; Tang, Qingsong; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Liu, Chengyu] NHLBI, Transgen Mouse Facil, NIH, Bethesda, MD 20892 USA.
[Wang, Chaochen; Ge, Kai] Natl Inst Diabet & Digest & Kidney Dis, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA.
[Levens, David] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Crane-Robinson, Colyn] Univ Portsmouth, Biophys Labs, Portsmouth PO1 2DT, Hants, England.
RP Zhao, KJ (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM zhaok@nhlbi.nih.gov
RI HU, GANGQING/K-5849-2012; Levens, David/C-9216-2009;
OI Levens, David/0000-0002-7616-922X; Ge, Kai/0000-0002-7442-5138
FU NHLBI, NIH
FX We thank Zhibin Wang, Dustin E. Schones, Iouri Chepelev, Brian J.
Abraham, Gang Wei, Daniel Kraushaar, and Benjamin Kidder for helpful
discussions. The DNA Sequencing Core and the Flow Cytometry Core of the
National Institute of Heart, Lung, and Blood Institute (NHLBI) assisted
with this work. Support was provided by the Division of Intramural
Research Program of the NHLBI, NIH.
NR 52
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U2 22
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 FEB 7
PY 2013
VL 12
IS 2
BP 180
EP 192
DI 10.1016/j.stem.2012.11.003
PG 13
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 287VB
UT WOS:000329569300009
PM 23260488
ER
PT J
AU Pepin, KM
Wang, J
Webb, CT
Hoeting, JA
Poss, M
Hudson, PJ
Hong, WS
Zhu, HC
Guan, Y
Riley, S
AF Pepin, Kim M.
Wang, Jia
Webb, Colleen T.
Hoeting, Jennifer A.
Poss, Mary
Hudson, Peter J.
Hong, Wenshan
Zhu, Huachen
Guan, Yi
Riley, Steven
TI Anticipating the Prevalence of Avian Influenza Subtypes H9 and H5 in
Live-Bird Markets
SO PLOS ONE
LA English
DT Article
ID TRANSMISSION CHARACTERISTICS; PANDEMIC PREPAREDNESS;
MATHEMATICAL-MODELS; RELATIVE-HUMIDITY; MEASLES EPIDEMICS; HUMAN
INFECTIONS; COUNT DATA; A VIRUS; DYNAMICS; TEMPERATURE
AB An ability to forecast the prevalence of specific subtypes of avian influenza viruses (AIV) in live-bird markets would facilitate greatly the implementation of preventative measures designed to minimize poultry losses and human exposure. The minimum requirement for developing predictive quantitative tools is surveillance data of AIV prevalence sampled frequently over several years. Recently, a 4-year time series of monthly sampling of hemagglutinin subtypes 1-13 in ducks, chickens and quail in live-bird markets in southern China has become available. We used these data to investigate whether a simple statistical model, based solely on historical data (variables such as the number of positive samples in host X of subtype Y time t months ago), could accurately predict prevalence of H5 and H9 subtypes in chickens. We also examined the role of ducks and quail in predicting prevalence in chickens within the market setting because between-species transmission is thought to occur within markets but has not been measured. Our best statistical models performed remarkably well at predicting future prevalence (pseudo-R-2 = 0.57 for H9 and 0.49 for H5), especially considering the multi-host, multi-subtype nature of AIVs. We did not find prevalence of H5/H9 in ducks or quail to be predictors of prevalence in chickens within the Chinese markets. Our results suggest surveillance protocols that could enable more accurate and timely predictive statistical models. We also discuss which data should be collected to allow the development of mechanistic models.
C1 [Pepin, Kim M.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Pepin, Kim M.; Webb, Colleen T.] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA.
[Wang, Jia; Hong, Wenshan; Zhu, Huachen; Guan, Yi] Shantou Univ, Coll Med, Int Inst Infect & Immun, Shantou, Peoples R China.
[Wang, Jia; Zhu, Huachen; Guan, Yi; Riley, Steven] Univ Hong Kong, State Key Lab Emerging Infect Dis, Hong Kong, Hong Kong, Peoples R China.
[Hoeting, Jennifer A.] Colorado State Univ, Dept Stat, Ft Collins, CO 80523 USA.
[Poss, Mary; Hudson, Peter J.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Riley, Steven] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Infect Dis Epidemiol, London, England.
RP Guan, Y (reprint author), Shantou Univ, Coll Med, Int Inst Infect & Immun, Shantou, Peoples R China.
EM yguan@hkucc.hku.hk; s.riley@imperial.ac.uk
RI Zhu, Huachen/A-8252-2017
OI Zhu, Huachen/0000-0003-2711-0501
FU RAPIDD program of the Science and Technology Directorate; U.S.
Department of Homeland Security; Fogarty International Center, NIH; NIH
Fogarty Center [R01 TW008246-01]; Wellcome Trust [093488/Z/10/Z];
Medical Research Council (UK) [MR/J008761/1]; European Union
[278433-PREDEMICS]
FX This work was supported by the RAPIDD program of the Science and
Technology Directorate, U.S. Department of Homeland Security, and the
Fogarty International Center, NIH. SR was also funded by: the NIH
Fogarty Center (R01 TW008246-01), the Wellcome Trust (University Award
093488/Z/10/Z), The Medical Research Council (UK, Project Grant
MR/J008761/1) and European Union Seventh Framework Programme
(FP7/2007-2013, Grant Agreement no278433-PREDEMICS). 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 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 FEB 7
PY 2013
VL 8
IS 2
AR e56157
DI 10.1371/journal.pone.0056157
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092XV
UT WOS:000315157200118
PM 23409145
ER
PT J
AU Girirajan, S
Dennis, MY
Baker, C
Malig, M
Coe, BP
Campbell, CD
Mark, K
Vu, TH
Alkan, C
Cheng, Z
Biesecker, LG
Bernier, R
Eichler, EE
AF Girirajan, Santhosh
Dennis, Megan Y.
Baker, Carl
Malig, Maika
Coe, Bradley P.
Campbell, Catarina D.
Mark, Kenneth
Vu, Tiffany H.
Alkan, Can
Cheng, Ze
Biesecker, Leslie G.
Bernier, Raphael
Eichler, Evan E.
TI Refinement and Discovery of New Hotspots of Copy-Number Variation
Associated with Autism Spectrum Disorder
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; DE-NOVO MUTATIONS; 17Q21.31 MICRODELETION
SYNDROME; STRUCTURAL VARIATION; DIAGNOSTIC INTERVIEW; HUMAN-DISEASE;
KANSL1 CAUSE; GENE; DUPLICATIONS; RESOURCE
AB Rare copy-number variants (CNVs) have been implicated in autism and intellectual disability. These variants are large and affect many genes but lack clear specificity toward autism as opposed to developmental-delay phenotypes. We exploited the repeat architecture of the genome to target segmental duplication-mediated rearrangement hotspots (n = 120, median size 1.78 Mbp, range 240 kbp to 13 Mbp) and smaller hotspots flanked by repetitive sequence (n = 1,247, median size 79 kbp, range 3-96 kbp) in 2,588 autistic individuals from simplex and multiplex families and in 580 controls. Our analysis identified several recurrent large hotspot events, including association with 1q21 duplications, which are more likely to be identified in individuals with autism than in those with developmental delay (p = 0.01; OR = 2.7). Within larger hotspots, we also identified smaller atypical CNVs that implicated CHD1L and ACACA for the 1q21 and 17q12 deletions, respectively. Our analysis, however, suggested no overall increase in the burden of smaller hotspots in autistic individuals as compared to controls. By focusing on gene-disruptive events, we identified recurrent CNVs, including DPP10, PLCB1, TRPM1, NRXN1, FHIT, and HYDIN, that are enriched in autism. We found that as the size of deletions increases, nonverbal IQ significantly decreases, but there is no impact on autism severity; and as the size of duplications increases, autism severity significantly increases but nonverbal IQ is not affected. The absence of an increased burden of smaller CNVs in individuals with autism and the failure of most large hotspots to refine to single genes is consistent with a model where imbalance of multiple genes contributes to a disease state.
C1 [Girirajan, Santhosh; Dennis, Megan Y.; Baker, Carl; Malig, Maika; Coe, Bradley P.; Campbell, Catarina D.; Mark, Kenneth; Vu, Tiffany H.; Alkan, Can; Cheng, Ze; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Bernier, Raphael] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA.
[Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
RP Eichler, EE (reprint author), Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
EM eee@gs.washington.edu
RI Alkan, Can/D-2982-2009; Coe, Bradley/A-2878-2009;
OI Alkan, Can/0000-0002-5443-0706; Mark, Kenneth/0000-0003-1867-6212
FU US National Institutes of Health (NIH) Ruth L. Kirchstein National
Research Service Award (NRSA) Fellowship through Eunice Kennedy Shriver
National Institute of Child Health and Human Development [F32HD071698];
NIH National Human Genome Research Institute NRSA [F32HG006070]; Simons
Foundation Autism Research Initiative award SFARI [137578]; NIH
[HD065285]
FX We thank Tonia Brown, Emre Karakoc, Nik Krumm, Arthur Ko, Daryl Dhanraj,
Jason Lu, John Huddleston, and Ben Nelson for valuable discussions and
technical assistance. We also thank the Autism Genetic Resource Exchange
(AGRE) for providing DNA samples. We are grateful to all of the families
at the participating Simons Simplex Collection (SSC) sites, as well as
the principal investigators (A. Beaudet, R. Bernier, J. Constantino, E.
Cook, E. Fombonne, D. Geschwind, R. Goin-Kochel, E. Hanson, D. Grice, A.
Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles,
O. Ousley, K. Pelphrey, B. Peterson, J. Piggot, C. Saulnier, M. State,
W. Stone, J. Sutcliffe, C. Walsh, Z. Warren, and E. Wijsman). We
appreciate obtaining access to phenotypic data on SFARI Base. Approved
researchers can obtain the SSC population dataset described in this
study by applying at Simons Simplex Collection online (see Web
Resources). M.Y.D. is supported by a US National Institutes of Health
(NIH) Ruth L. Kirchstein National Research Service Award (NRSA)
Fellowship through Eunice Kennedy Shriver National Institute of Child
Health and Human Development (F32HD071698). C.D.C. was supported by NIH
National Human Genome Research Institute NRSA (F32HG006070). This work
was supported by Simons Foundation Autism Research Initiative award
SFARI 137578 (E.E.E.) and NIH grant HD065285 (E.E.E.). E.E.E. is an
investigator with the Howard Hughes Medical Institute.
NR 59
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD FEB 7
PY 2013
VL 92
IS 2
BP 221
EP 237
DI 10.1016/j.ajhg.2012.12.016
PG 17
WC Genetics & Heredity
SC Genetics & Heredity
GA 093GL
UT WOS:000315179600006
PM 23375656
ER
PT J
AU Hammer, MB
Eleuch-Fayache, G
Schottlaender, LV
Nehdi, H
Gibbs, JR
Arepalli, SK
Chong, SB
Hernandez, DG
Sailer, A
Liu, GX
Mistry, PK
Cai, HB
Shrader, G
Sassi, C
Bouhlal, Y
Houlden, H
Hentati, F
Amouri, R
Singleton, AB
AF Hammer, Monia B.
Eleuch-Fayache, Ghada
Schottlaender, Lucia V.
Nehdi, Houda
Gibbs, J. Raphael
Arepalli, Sampath K.
Chong, Sean B.
Hernandez, Dena G.
Sailer, Anna
Liu, Guoxiang
Mistry, Pramod K.
Cai, Huaibin
Shrader, Ginamarie
Sassi, Celeste
Bouhlal, Yosr
Houlden, Henry
Hentati, Faycal
Amouri, Rim
Singleton, Andrew B.
TI Mutations in GBA2 Cause Autosomal-Recessive Cerebellar Ataxia with
Spasticity
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID ACID BETA-GLUCOSIDASE; NONLYSOSOMAL GLUCOSYLCERAMIDASE;
BETA-GLUCOSIDASE-2; DISEASE; FEATURES
AB Autosomal-recessive cerebellar ataxia (ARCA) comprises a large and heterogeneous group of neurodegenerative disorders with more than 20 different forms currently recognized, many of which are also associated with increased tone and some of which have limb spasticity. Gaucher disease is a lysosomal storage disease resulting from a defect in the enzyme acid beta-glucosidase 1. beta-glucosidase 2 is an enzyme with similar glucosylceramidase activity but to date has not been associated with a monogenic disorder. We studied four unrelated consanguineous families of Tunisian decent diagnosed with cerebellar ataxia of unknown origin. We performed homozygosity mapping and whole-exome sequencing in an attempt to identify the genetic origin of their disorder. We were able to identify mutations responsible for autosomal-recessive ataxia in these families within the gene encoding beta-glucosidase 2, GBA2. Two nonsense mutations (c.363C>A [p.Tyr121*] and c.1018C>T [p.Arg340*]) and a substitution (c.2618G>A [p.Arg873His]) were identified, probably resulting in nonfunctional enzyme. This study suggests GBA2 mutations are a cause of recessive spastic ataxia and responsible for a form of glucosylceramide storage disease in humans.
C1 [Hammer, Monia B.; Gibbs, J. Raphael; Arepalli, Sampath K.; Chong, Sean B.; Hernandez, Dena G.; Liu, Guoxiang; Cai, Huaibin; Shrader, Ginamarie; Sassi, Celeste; Singleton, Andrew B.] NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Hammer, Monia B.; Eleuch-Fayache, Ghada; Nehdi, Houda; Hentati, Faycal; Amouri, Rim] Natl Inst Neurol, Dept Mol Neurobiol & Neuropathol, Tunis 1007, Tunisia.
[Schottlaender, Lucia V.; Gibbs, J. Raphael; Hernandez, Dena G.; Sailer, Anna; Sassi, Celeste; Houlden, Henry] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Schottlaender, Lucia V.; Sailer, Anna; Houlden, Henry] UCL Inst Neurol, MRC Ctr Neuromuscular Dis, London WC1N 3BG, England.
[Schottlaender, Lucia V.; Sailer, Anna; Houlden, Henry] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England.
[Gibbs, J. Raphael; Hernandez, Dena G.; Sassi, Celeste] UCL Inst Neurol, Reta Lila Weston Labs, London WC1N 3BG, England.
[Mistry, Pramod K.] Yale Univ, Dept Pediat & Med, Sch Med, Sect Pediat Gastroenterol & Hepatol, New Haven, CT 06520 USA.
[Bouhlal, Yosr] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
RP Singleton, AB (reprint author), NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
EM singleta@mail.nih.gov
RI Cai, Huaibin/H-3359-2013; Houlden, Henry/C-1532-2008; liu,
guoxiang/I-8174-2013; Singleton, Andrew/C-3010-2009
OI Cai, Huaibin/0000-0002-8596-6108; Houlden, Henry/0000-0002-2866-7777;
FU National Institute on Aging, National Institutes of Health, part of the
Department of Health and Human Services [ZIA AG000958-09]; National
Ataxia Foundation; Medical Research Council (MRC); Brain Research Trust;
NORD; MRC/Wellcome Trust Parkinson's disease consortium; UCLH/UCL
Department of Health's NIHR Biomedical Research Centres
FX The authors thank J. Hammer for his contribution in the correction of
the manuscript and his help with the figures. We also thank the affected
individuals and their families for taking part in this work. This work
was supported in part by the Intramural Research Program of the National
Institute on Aging, National Institutes of Health, part of the
Department of Health and Human Services (project number ZIA AG000958-09)
and the National Ataxia Foundation. We are also grateful to the Medical
Research Council (MRC), the Brain Research Trust, and NORD for funding
to H.H., L.V.S., and A.S. and also the MRC/Wellcome Trust Parkinson's
disease consortium grant and the UCLH/UCL Department of Health's NIHR
Biomedical Research Centres funding scheme.
NR 20
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U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD FEB 7
PY 2013
VL 92
IS 2
BP 245
EP 251
DI 10.1016/j.ajhg.2012.12.012
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 093GL
UT WOS:000315179600008
PM 23332917
ER
PT J
AU Lindsley, DL
Roote, J
Kennison, JA
AF Lindsley, Dan L.
Roote, John
Kennison, James A.
TI Anent the Genomics of Spermatogenesis in Drosophila melanogaster
SO PLOS ONE
LA English
DT Article
ID BIASED GENE-EXPRESSION; STERILE MUTATIONS; MALE-FERTILITY; X-CHROMOSOME;
REGION; DEMASCULINIZATION; LETHAL
AB An appreciable fraction of the Drosophila melanogaster genome is dedicated to male fertility. One approach to characterizing this subset of the genome is through the study of male-sterile mutations. We studied the relation between vital and male-fertility genes in three large autosomal regions that were saturated for lethal and male-sterile mutations. The majority of male-sterile mutations affect genes that are exclusively expressed in males. These genes are required only for male fertility, and several mutant alleles of each such gene were encountered. A few male-sterile mutations were alleles of vital genes that are expressed in both males and females. About one-fifth of the genes in Drosophila melanogaster show male-specific expression in adults. Although some earlier studies found a paucity of genes on the X chromosome showing male-biased expression, we did not find any significant differences between the X chromosome and the autosomes either in the relative frequencies of mutations to male sterility or in the frequencies of genes with male-specific expression in adults. Our results suggest that as much as 25% of the Drosophila genome may be dedicated to male fertility.
C1 [Lindsley, Dan L.] Univ Calif San Diego, Dept Cell & Dev Biol, La Jolla, CA 92093 USA.
[Roote, John] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England.
[Kennison, James A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
RP Kennison, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM Jim_Kennison@nih.gov
FU Intramural Research Program of the National Institutes of Health, Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD); Department of Genetics, University of Cambridge
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD) and the
Department of Genetics, University of Cambridge. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 29
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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 FEB 7
PY 2013
VL 8
IS 2
AR e55915
DI 10.1371/journal.pone.0055915
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092XV
UT WOS:000315157200089
PM 23409089
ER
PT J
AU Shimizu, YK
Hijikata, M
Oshima, M
Shimizu, K
Alter, HJ
Purcell, RH
Yoshikura, H
Hotta, H
AF Shimizu, Yohko K.
Hijikata, Minako
Oshima, Masamichi
Shimizu, Kazufumi
Alter, Harvey J.
Purcell, Robert H.
Yoshikura, Hiroshi
Hotta, Hak
TI Isolation of Human Monoclonal Antibodies to the Envelope E2 Protein of
Hepatitis C Virus and Their Characterization
SO PLOS ONE
LA English
DT Article
ID CELL-CULTURE SYSTEMS; NON-B HEPATITIS; NEUTRALIZING ANTIBODIES; NON-A;
GLYCOPROTEIN; INFECTION; IDENTIFICATION; CHIMPANZEES; BINDING; ESCAPE
AB We isolated and characterized two human monoclonal antibodies to the envelope E2 protein of hepatitis C virus (HCV). Lymphoblastoid cell lines stably producing antibodies were obtained by immortalizing peripheral blood mononuclear cells of a patient with chronic hepatitis C using Epstein-Barr virus. Screening for antibody-positive clones was carried out by immunofluorescence with Huh7 cells expressing the E2 protein of HCV strain H (genotype 1a) isolated from the same patient. Isotype of resulting antibodies, #37 and #55, was IgG1/kappa and IgG1/lambda, respectively. Epitope mapping revealed that #37 and #55 recognize conformational epitopes spanning amino acids 429 to 652 and 508 to 607, respectively. By immunofluorescence using virus-infected Huh7.5 cells as targets both antibodies were reactive with all of the nine different HCV genotypes/subtypes tested. The antibodies showed a different pattern of immuno-staining; while #37 gave granular reactions mostly located in the periphery of the nucleus, #55 gave diffuse staining throughout the cytoplasm. Both antibodies were shown by immuno-gold electron microscopy to bind to intact viral particles. In a neutralization assay (focus-forming unit reduction using chimeric infectious HCV containing structural proteins derived from genotypes 1a, 1b, 2a, 2b, 3a, 4a, 5a, 6a, and 7a), #55 inhibited the infection of all HCV genotypes tested but genotype 7a to a lesser extent. #37 did not neutralize any of these viruses. As a broadly cross-neutralizing human antibody, #55 may be useful for passive immunotherapy of HCV infection.
C1 [Shimizu, Yohko K.; Hotta, Hak] Kobe Univ, Div Microbiol, Ctr Infect Dis, Grad Sch Med, Kobe, Hyogo 657, Japan.
[Hijikata, Minako] Natl Ctr Global Hlth & Med, Dept Resp Dis, Res Inst, Tokyo, Japan.
[Oshima, Masamichi] Natl Inst Infect Dis, Dept Immunol, Tokyo, Japan.
[Shimizu, Kazufumi] Nihon Univ, Sch Med, Dept Gynecol, Tokyo, Japan.
[Alter, Harvey J.] NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Purcell, Robert H.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Yoshikura, Hiroshi] Minist Hlth Labor & Welf, Food Safety Div, Tokyo, Japan.
RP Shimizu, YK (reprint author), Kobe Univ, Div Microbiol, Ctr Infect Dis, Grad Sch Med, Kobe, Hyogo 657, Japan.
EM yshimizu@nih.go.jp
FU Science and Technology Partnership for Sustainable Development (SATREPS)
program of Japan; Science and Technology Agency (JST); Japan
International Cooperation Agency (JICA); Intramural Research Program of
the National Institute of Allergy and Infectious Diseases
FX This work was supported, in part, by the Science and Technology
Partnership for Sustainable Development (SATREPS) program of Japan
Science and Technology Agency (JST) and Japan International Cooperation
Agency (JICA) and the Intramural Research Program of the 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 28
TC 1
Z9 1
U1 0
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 7
PY 2013
VL 8
IS 2
AR e55874
DI 10.1371/journal.pone.0055874
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092XV
UT WOS:000315157200082
PM 23409074
ER
PT J
AU Fulzele, K
Krause, DS
Panaroni, C
Saini, V
Barry, KJ
Liu, XL
Lotinun, S
Baron, R
Bonewald, L
Feng, JQ
Chen, M
Weinstein, LS
Wu, JY
Kronenberg, HM
Scadden, DT
Pajevic, PD
AF Fulzele, Keertik
Krause, Daniela S.
Panaroni, Cristina
Saini, Vaibhav
Barry, Kevin J.
Liu, Xiaolong
Lotinun, Sutada
Baron, Roland
Bonewald, Lynda
Feng, Jian Q.
Chen, Min
Weinstein, Lee S.
Wu, Joy Y.
Kronenberg, Henry M.
Scadden, David T.
Pajevic, Paola Divieti
TI Myelopoiesis is regulated by osteocytes through Gs alpha-dependent
signaling
SO BLOOD
LA English
DT Article
ID STEM-CELL NICHE; HEMATOPOIETIC STEM; BONE-FORMATION; G-PROTEIN;
PROGENITOR CELLS; RECEPTOR; OSTEOBLASTS; SCLEROSTIN; MARROW;
DIFFERENTIATION
AB Hematopoietic progenitors are regulated in their respective niches by cells of the bone marrow microenvironment. The bone marrow microenvironment is composed of a variety of cell types, and the relative contribution of each of these cells for hematopoietic lineage maintenance has remained largely unclear. Osteocytes, the most abundant yet least understood cells in bone, are thought to initiate adaptive bone remodeling responses via osteoblasts and osteoclasts. Here we report that these cells regulate hematopoiesis, constraining myelopoiesis through a Gs alpha-mediated mechanism that affects G-CSF production. Mice lacking Gs alpha in osteocytes showed a dramatic increase in myeloid cells in bone marrow, spleen, and peripheral blood. This hematopoietic phenomenon was neither intrinsic to the hematopoietic cells nor dependent on osteoblasts but was a consequence of an altered bone marrow microenvironment imposed by Gs alpha deficiency in osteocytes. Conditioned media from osteocyte-enriched bone explants significantly increased myeloid colony formation in vitro, which was blocked by G-CSF-neutralizing antibody, indicating a critical role of osteocyte-derived G-CSF in the myeloid expansion. (Blood. 2013;121(6):930-939)
C1 [Fulzele, Keertik; Panaroni, Cristina; Saini, Vaibhav; Barry, Kevin J.; Liu, Xiaolong; Baron, Roland; Wu, Joy Y.; Kronenberg, Henry M.; Pajevic, Paola Divieti] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA.
[Krause, Daniela S.; Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA.
[Lotinun, Sutada; Baron, Roland] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Bonewald, Lynda] Univ Missouri, Dept Oral Biol, Kansas City, MO 64110 USA.
[Feng, Jian Q.] Baylor Coll Dent, Dept Biomed Sci, Texas A&M Hlth Sci Ctr, Dallas, TX 75246 USA.
[Chen, Min; Weinstein, Lee S.] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Pajevic, PD (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier 1101, Boston, MA 02114 USA.
EM divieti@helix.mgh.harvard.edu
FU National Institutes of Health [AR060221, DK079161, K08CA138916];
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health; Harvard Stem Cell Institute
FX This work was supported by the National Institutes of Health (grants
AR060221 and DK079161, P. D. P.; grant K08CA138916, D. S. K.), the
Intramural Research Program of National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health (L. S. W.),
and the Harvard Stem Cell Institute (J.Y.W.).
NR 33
TC 46
Z9 46
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 FEB 7
PY 2013
VL 121
IS 6
BP 930
EP 939
DI 10.1182/blood-2012-06-437160
PG 10
WC Hematology
SC Hematology
GA 088WO
UT WOS:000314868800014
PM 23160461
ER
PT J
AU Genest, O
Reidy, M
Street, TO
Hoskins, JR
Camberg, JL
Agard, DA
Masison, DC
Wickner, S
AF Genest, Olivier
Reidy, Michael
Street, Timothy O.
Hoskins, Joel R.
Camberg, Jodi L.
Agard, David A.
Masison, Daniel C.
Wickner, Sue
TI Uncovering a Region of Heat Shock Protein 90 Important for Client
Binding in E. coli and Chaperone Function in Yeast
SO MOLECULAR CELL
LA English
DT Article
ID CONFORMATIONAL DYNAMICS; MOLECULAR CHAPERONE; ATPASE ACTIVITY;
SUBSTRATE-BINDING; TERMINAL DIMERIZATION; STRUCTURAL-ANALYSIS;
CRYSTAL-STRUCTURE; STEROID-RECEPTOR; HSP90; DOMAIN
AB The heat shock protein 90 (Hsp90) family of heat shock proteins is an abundantly expressed and highly conserved family of ATP-dependent molecular chaperones. Hsp90 facilitates remodeling and activation of hundreds of proteins. In this study, we developed a screen to identify Hsp90-defective mutants in E. coli. The mutations obtained define a region incorporating residues from the middle and C-terminal domains of E. coli Hsp90. The mutant proteins are defective in chaperone activity and client binding in vitro. We constructed homologous mutations in S. cerevisiae Hsp82 and identified several that caused defects in chaperone activity in vivo and in vitro. However, the Hsp82 mutant proteins were less severely defective in client binding to a model substrate than the corresponding E. coli mutant proteins. Our results identify a region in Hsp90 important for client binding in E. coli Hsp90 and suggest an evolutionary divergence in the mechanism of client interaction by bacterial and yeast Hsp90.
C1 [Genest, Olivier; Hoskins, Joel R.; Camberg, Jodi L.; Wickner, Sue] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Reidy, Michael; Masison, Daniel C.] NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
[Street, Timothy O.; Agard, David A.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
[Agard, David A.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
RP Wickner, S (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM wickners@mail.nih.gov
OI Reidy, Michael/0000-0002-9290-7595
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research; National Institute of Diabetes and Digestive
and Kidney Diseases; Howard Hughes Medical Institute
FX We thank Jill Johnson (University of Idaho) for the Ste11 Delta N
plasmid, Len Neckers (NCI) for yeast plasmids, and Shannon Doyle and
Danielle Johnston for critical reading of the manuscript and helpful
discussions. This research was supported by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research, National Institute of Diabetes and Digestive and Kidney
Diseases, and Howard Hughes Medical Institute. O.G., J.R.H., T.O.S.,
J.L.C., and M.R. designed experiments, performed experiments,
interpreted data, and wrote the paper; S.W., D.A.A., and D.C.M. designed
experiments, interpreted data, and wrote the paper.
NR 46
TC 30
Z9 30
U1 1
U2 26
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD FEB 7
PY 2013
VL 49
IS 3
BP 464
EP 473
DI 10.1016/j.molcel.2012.11.017
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 087VO
UT WOS:000314792500010
PM 23260660
ER
PT J
AU Zuo, W
Huang, F
Chiang, YJ
Li, M
Du, J
Ding, Y
Zhang, T
Lee, HW
Jeong, LS
Chen, YL
Deng, HT
Feng, XH
Luo, SW
Gao, CJ
Chen, YG
AF Zuo, Wei
Huang, Fei
Chiang, Y. Jeffrey
Li, Meng
Du, Jun
Ding, Yi
Zhang, Ting
Lee, Hyuk Woo
Jeong, Lak Shin
Chen, Yuling
Deng, Haiteng
Feng, Xin-Hua
Luo, Shiwen
Gao, Chunji
Chen, Ye-Guang
TI c-Cbl-Mediated Neddylation Antagonizes Ubiquitination and Degradation of
the TGF-beta Type II Receptor
SO MOLECULAR CELL
LA English
DT Article
ID REGULATORY T-CELLS; HEMATOPOIETIC STEM-CELLS; GROWTH-FACTOR-BETA;
MYELOID-LEUKEMIA; ENDOCYTIC REGULATION; TYROSINE KINASES; IN-VIVO;
NEDD8; LIGASE; PROTEIN
AB Transforming growth factor beta (TGF-beta) is a potent antiproliferative factor in multiple types of cells. Deregulation of TGF-beta signaling is associated with the development of many cancers, including leukemia, though the molecular mechanisms are largely unclear. Here, we show that Casitas B-lineage lymphoma (c-Cbl), a known proto-oncogene encoding an ubiquitin E3 ligase, promotes TGF-beta signaling by neddylating and stabilizing the type II receptor (T beta RII). Knockout of c-Cbl decreases the T beta RII protein level and desensitizes hematopoietic stem or progenitor cells to TGF-beta stimulation, while c-Cbl overexpression stabilizes T beta RII and sensitizes leukemia cells to TGF-beta. c-Cbl conjugates neural precursor cell-expressed, developmentally downregulated 8 (NEDD8), a ubiquitin-like protein, to T beta RII at Lys556 and Lys567. Neddylation of T beta RII promotes its endocytosis to EEA1-positive early endosomes while preventing its endocytosis to caveolin-positive compartments, therefore inhibiting T beta RII ubiquitination and degradation. We have also identified a neddylation-activity-defective c-Cbl mutation from leukemia patients, implying a link between aberrant T beta RII neddylation and leukemia development.
C1 [Zuo, Wei; Huang, Fei; Du, Jun; Ding, Yi; Zhang, Ting; Chen, Ye-Guang] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Tsinghua Peking Ctr Life Sci, Sch Life Sci, Beijing 100084, Peoples R China.
[Chen, Yuling; Deng, Haiteng] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
[Chiang, Y. Jeffrey] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Li, Meng; Gao, Chunji] Chinese Peoples Liberat Army Gen Hosp, Ctr Hematol, Beijing 100853, Peoples R China.
[Lee, Hyuk Woo; Jeong, Lak Shin] Ewha Womans Univ, Dept Bioinspired Sci, Seoul 120750, South Korea.
[Feng, Xin-Hua] Zhejiang Univ, Inst Life Sci, Hangzhou 310058, Zhejiang, Peoples R China.
[Luo, Shiwen] Nanchang Univ, Affiliated Hosp 1, Nanchang 330006, Jiangxi, Peoples R China.
RP Chen, YG (reprint author), Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Tsinghua Peking Ctr Life Sci, Sch Life Sci, Beijing 100084, Peoples R China.
EM ygchen@mail.tsinghua.edu.cn
FU 973 Program [2010CB833706, 2011CB943803]; National Natural Science
Foundation of China [30930050, 30921004]; Tsinghua University Initiative
Scientific Research Program [2010THZ0]; Intramural Research Program of
the National Institutes of Health (NIH), National Cancer Institute
FX We thank Drs. Wallace Y. Langdon, Stanley Lipkowitz, and Xuetao Cao for
c-Cbl and Cbl-b constructs, Drs. Qiang Wang and Chengcheng Jin for
generating the anti-T beta RII (ECD) antibody, Dr. Jun Wen for technical
assistance, and Drs. Hai Qi, Wei Guo and Li Yu for helpful suggestions.
This work was supported by grants from the 973 Program (2010CB833706,
2011CB943803), the National Natural Science Foundation of China
(30930050, 30921004), and the Tsinghua University Initiative Scientific
Research Program (2010THZ0) to Y.G.C. This research was also supported
by the Intramural Research Program of the National Institutes of Health
(NIH), National Cancer Institute to Y.J.C.
NR 48
TC 36
Z9 37
U1 2
U2 33
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 FEB 7
PY 2013
VL 49
IS 3
BP 499
EP 510
DI 10.1016/j.molcel.2012.12.002
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 087VO
UT WOS:000314792500013
PM 23290524
ER
PT J
AU Arpitha, P
Gao, CY
Tripathi, BK
Saravanamuthu, S
Zelenka, P
AF Arpitha, Parthasarathy
Gao, Chun Y.
Tripathi, Brajendra K.
Saravanamuthu, Senthil
Zelenka, Peggy
TI Cyclin-dependent kinase 5 promotes the stability of corneal epithelial
cell junctions
SO MOLECULAR VISION
LA English
DT Article
ID CANINE KIDNEY-CELLS; E-CADHERIN; P120 CATENIN; ACTIN CYTOSKELETON;
ADHERENS JUNCTIONS; RHO ACTIVITY; ADHESION; CDK5; P120-CATENIN;
ACTIVATION
AB Purpose: Although cyclin-dependent kinase 5 (Cdk5) inhibits the formation of junctions containing N-cadherin, the effect of Cdk5 on junctions containing E-cadherin is less clear. The present study investigates the functional significance of Cdk5 in forming and maintaining cell-cell stability in corneal epithelial cells.
Methods: A Cdk5-deficient human corneal limbal epithelial cell line was generated by lentiviral transduction of small hairpin RNA specific for Cdk5 (shCdk5-HCLE cells). A blasticidin-inducible vector for expression of Cdk5-specific short hairpin RNA (ShCdk5) was generated by recombination and packaged into non-replicative lentiviral particles for transduction of human corneal limbal epithelial (HCLE) cells. Blasticidin-resistant cells were isolated for analysis. Cell aggregations were performed using HCLE, Cdk5 inhibitor olomoucine, ShCdk5, and MDA-MB 231 cells in the presence and absence of calcium, and particle size was measured using image analysis software. Relative protein concentrations were measured with immunoblotting and quantitative densitometry. Total internal reflection fluorescence (TIRF) microscopy was performed on cells transfected with green fluorescent protein (GFP)-E-cadherin or GFP-p120, and internalization of boundary-localized proteins was analyzed with particle tracking software. The stability of surface-exposed proteins was determined by measuring the recovery of biotin-labeled proteins with affinity chromatography. Rho and Rac activity was measured with affinity chromatography and immunoblotting.
Results: Examining the effect of Cdk5 on E-cadherin containing epithelial cell-cell adhesions using a corneal epithelial cell line (HCLE), we found that Cdk5 and Cdk5 (pY15) coimmunoprecipitate with E-cadherin and Cdk5 (pY15) colocalizes with E-cadherin at cell-cell junctions. Inhibiting Cdk5 activity in HCLE or suppressing Cdk5 expression in a stable HCLE-derived cell line (ShHCLE) decreased calcium-dependent cell adhesion, promoted the cytoplasmic localization of E-cadherin, and accelerated the loss of surface-biotinylated E-cadherin. TIRF microscopy of GFP-E-cadherin in transfected HCLE cells showed an actively internalized sub-population of E-cadherin, which was not bound to p120 as it was trafficked away from the cell-cell boundary. This population increased in the absence of Cdk5 activity, suggesting that Cdk5 inhibition promotes dissociation of p120/E-cadherin junctional complexes. These effects of Cdk5 inhibition or suppression were accompanied by decreased Rac activity, increased Rho activity, and enhanced binding of E-cadherin to the Rac effector Ras GTPase-activating-like protein (IQGAP1). Cdk5 inhibition also reduced adhesion in a cadherin-deficient cell line (MDA-MB-231) expressing exogenous E-cadherin, although Cdk5 inhibition promoted adhesion when these cells were transfected with N-cadherin, as previous studies of Cdk5 and N-cadherin predicted. Moreover, Cdk5 inhibition induced N-cadherin expression and formation of N-cadherin/p120 complexes in HCLE cells.
Conclusions: These results indicate that loss of Cdk5 activity destabilizes junctional complexes containing E-cadherin, leading to internalization of E-cadherin and upregulation of N-cadherin. Thus, Cdk5 activity promotes stability of E-cadherin-based cell-cell junctions and inhibits the E-cadherin-to-N-cadherin switch typical of epithelial-mesenchymal transitions.
C1 [Arpitha, Parthasarathy; Gao, Chun Y.; Tripathi, Brajendra K.; Saravanamuthu, Senthil; Zelenka, Peggy] NEI, NIH, Rockville, MD 20852 USA.
[Gao, Chun Y.] NEI, NIH, Bethesda, MD 20892 USA.
RP Arpitha, P (reprint author), NEI, NIH, Bldg 5635,Room 1S-02,Fishers Lane, Rockville, MD 20852 USA.
EM arpithaparthasarathy@yahoo.com
FU National Eye Institute, NIH [Z01EY000238]
FX This research is supported by Intramural Research Program, Z01EY000238,
National Eye Institute, NIH. We acknowledge use of HCLE cell line, a
generous gift of Dr. Ilene Gipson, Schepens Eye research Institute,
Boston; Dr. Keith Burridge, University of North Carolina, Chapel Hill
for p120 and E-cadherin clones and Dr. Robert Farris for confocal
imaging facility at the NEI/NIH core facility. Author-Arpitha
Parthasarathy1 is currently at the University of Kentucky,
Dept of Ophthalmology, Lexington
NR 50
TC 0
Z9 0
U1 0
U2 3
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD FEB 7
PY 2013
VL 19
BP 319
EP 332
PG 14
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 089LM
UT WOS:000314912000001
PM 23401660
ER
PT J
AU Shao, W
Zhang, SZ
Tang, M
Zhang, XH
Zhou, Z
Yin, YQ
Zhou, QB
Huang, YY
Liu, YJ
Wawrousek, E
Chen, T
Li, SB
Xu, M
Zhou, JN
Hu, G
Zhou, JW
AF Shao, Wei
Zhang, Shu-zhen
Tang, Mi
Zhang, Xin-hua
Zhou, Zheng
Yin, Yan-qing
Zhou, Qin-bo
Huang, Yuan-yuan
Liu, Ying-jun
Wawrousek, Eric
Chen, Teng
Li, Sheng-bin
Xu, Ming
Zhou, Jiang-ning
Hu, Gang
Zhou, Jia-wei
TI Suppression of neuroinflammation by astrocytic dopamine D2 receptors via
alpha B-crystallin
SO NATURE
LA English
DT Article
ID HUMAN-BRAIN; INFLAMMATION; DISEASE; MICROGLIA; PATHWAY; INNATE; MICE
AB Chronic neuroinflammation is a common feature of the ageing brain and some neurodegenerative disorders. However, the molecular and cellular mechanisms underlying the regulation of innate immunity in the central nervous system remain elusive. Here we show that the astrocytic dopamine D2 receptor (DRD2) modulates innate immunity through alpha B-crystallin (CRYAB), which is known to suppress neuroinflammation(1,2). We demonstrate that knockout mice lacking Drd2 showed remarkable inflammatory response in multiple central nervous system regions and increased the vulnerability of nigral dopaminergic neurons to neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity(3). Astrocytes null for Drd2 became hyper-responsive to immune stimuli with a marked reduction in the level of CRYAB. Preferential ablation of Drd2 in astrocytes robustly activated astrocytes in the substantia nigra. Gain- or loss-of-function studies showed that CRYAB is critical for DRD2-mediated modulation of innate immune response in astrocytes. Furthermore, treatment of wildtype mice with the selective DRD2 agonist quinpirole increased resistance of the nigral dopaminergic neurons to MPTP through partial suppression of inflammation. Our study indicates that astrocytic DRD2 activation normally suppresses neuroinflammation in the central nervous system through a CRYAB-dependent mechanism, and provides a new strategy for targeting the astrocyte-mediated innate immune response in the central nervous system during ageing and disease.
C1 [Shao, Wei; Zhang, Shu-zhen; Tang, Mi; Zhang, Xin-hua; Zhou, Zheng; Yin, Yan-qing; Zhou, Qin-bo; Huang, Yuan-yuan; Liu, Ying-jun; Zhou, Jia-wei] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, State Key Lab Neurosci, Shanghai 200031, Peoples R China.
[Tang, Mi; Hu, Gang] Nanjing Med Univ, Dept Pharmacol, Jiangsu Key Lab Neurodegenerat, Nanjing 210029, Jiangsu, Peoples R China.
[Wawrousek, Eric] NEI, NIH, Bethesda, MD 20892 USA.
[Chen, Teng; Li, Sheng-bin] Xi An Jiao Tong Univ, Sch Med, Dept Forens Sci, Xian 710061, Shanxi, Peoples R China.
[Xu, Ming] Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA.
[Zhou, Jiang-ning] Univ Sci & Technol China, Sch Life Sci, CAS Key Lab Brain Funct & Dis, Hefei 230027, Anhui, Peoples R China.
RP Zhou, JW (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, State Key Lab Neurosci, Shanghai 200031, Peoples R China.
EM jwzhou@ion.ac.cn
OI Zhou, Jiawei/0000-0002-1844-9178; Zhou, Qinbo/0000-0002-7967-2138
FU Chinese Academy of Sciences; National Basic Research Program of China
[2011CBA00408, 2011CB504102]; Natural Science Foundation of China
[31021063, 31123002]; Shanghai Metropolitan Fund for Research and
Development
FX We thank B. Zhang and Y.J. Yan for technical assistance; L. Zhu for
technical support in DNA microarray analysis; the Optical Imaging Center
of ION and the Cell Biology Analysis Center of IBCB for technical
support in confocal microscopy; T. L. Hagemann for providing the CRYAB
construct; R. Quinlan for anti-CRYAB antibodies, Y. Q. Ding for
providing the Drd1 and Drd2 gene null mice; we also thank Shanghai
Research Center for Model Organisms for creating Drd2-floxed mice. This
work was supported by grants from the Chinese Academy of Sciences,
National Basic Research Program of China (nos 2011CBA00408 and
2011CB504102), Natural Science Foundation of China (nos 31021063 and
31123002), and Shanghai Metropolitan Fund for Research and Development.
NR 22
TC 89
Z9 101
U1 4
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD FEB 7
PY 2013
VL 494
IS 7435
BP 90
EP 94
DI 10.1038/nature11748
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200040
PM 23242137
ER
PT J
AU Thanassoulis, G
Campbell, CY
Owens, DS
Smith, JG
Smith, AV
Peloso, GM
Kerr, KF
Pechlivanis, S
Budoff, MJ
Harris, TB
Malhotra, R
O'Brien, KD
Kamstrup, PR
Nordestgaard, BG
Tybjaerg-Hansen, A
Allison, MA
Aspelund, T
Criqui, MH
Heckbert, SR
Hwang, SJ
Liu, YM
Sjogren, M
van der Pals, J
Kalsch, H
Muhleisen, TW
Nothen, MM
Cupples, LA
Caslake, M
Di Angelantonio, E
Danesh, J
Rotter, JI
Sigurdsson, S
Wong, Q
Erbel, R
Kathiresan, S
Melander, O
Gudnason, V
O'Donnell, CJ
Post, WS
AF Thanassoulis, George
Campbell, Catherine Y.
Owens, David S.
Smith, J. Gustav
Smith, Albert V.
Peloso, Gina M.
Kerr, Kathleen F.
Pechlivanis, Sonali
Budoff, Matthew J.
Harris, Tamara B.
Malhotra, Rajeev
O'Brien, Kevin D.
Kamstrup, Pia R.
Nordestgaard, Borge G.
Tybjaerg-Hansen, Anne
Allison, Matthew A.
Aspelund, Thor
Criqui, Michael H.
Heckbert, Susan R.
Hwang, Shih-Jen
Liu, Yongmei
Sjogren, Marketa
van der Pals, Jesper
Kaelsch, Hagen
Muehleisen, Thomas W.
Noethen, Markus M.
Cupples, L. Adrienne
Caslake, Muriel
Di Angelantonio, Emanuele
Danesh, John
Rotter, Jerome I.
Sigurdsson, Sigurdur
Wong, Quenna
Erbel, Raimund
Kathiresan, Sekar
Melander, Olle
Gudnason, Vilmundur
O'Donnell, Christopher J.
Post, Wendy S.
CA CHARGE Extracoronary Calcium Worki
TI Genetic Associations with Valvular Calcification and Aortic Stenosis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY CALCIUM; RISK-FACTORS; VALVE
CALCIFICATION; MYOCARDIAL-INFARCTION; LP(A) LIPOPROTEIN; HEART-DISEASE;
LONG-TERM; DESIGN; ATHEROSCLEROSIS
AB Background
Limited information is available regarding genetic contributions to valvular calcification, which is an important precursor of clinical valve disease.
Methods
We determined genomewide associations with the presence of aortic-valve calcification (among 6942 participants) and mitral annular calcification (among 3795 participants), as detected by computed tomographic (CT) scanning; the study population for this analysis included persons of white European ancestry from three cohorts participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (discovery population). Findings were replicated in independent cohorts of persons with either CT-detected valvular calcification or clinical aortic stenosis.
Results
One SNP in the lipoprotein(a) (LPA) locus (rs10455872) reached genomewide significance for the presence of aortic-valve calcification (odds ratio per allele, 2.05; P = 9.0x10(-10)), a finding that was replicated in additional white European, African-American, and Hispanic-American cohorts (P<0.05 for all comparisons). Genetically determined Lp(a) levels, as predicted by LPA genotype, were also associated with aortic-valve calcification, supporting a causal role for Lp(a). In prospective analyses, LPA genotype was associated with incident aortic stenosis (hazard ratio per allele, 1.68; 95% confidence interval [CI], 1.32 to 2.15) and aortic-valve replacement (hazard ratio, 1.54; 95% CI, 1.05 to 2.27) in a large Swedish cohort; the association with incident aortic stenosis was also replicated in an independent Danish cohort. Two SNPs (rs17659543 and rs13415097) near the proinflammatory gene IL1F9 achieved genomewide significance for mitral annular calcification (P = 1.5x10(-8) and P = 1.8x10(-8), respectively), but the findings were not replicated consistently.
Conclusions
Genetic variation in the LPA locus, mediated by Lp(a) levels, is associated with aortic-valve calcification across multiple ethnic groups and with incident clinical aortic stenosis. (Funded by the National Heart, Lung, and Blood Institute and others.)
C1 [Thanassoulis, George] McGill Univ, Dept Med, Ctr Hlth, Montreal, PQ, Canada.
[Thanassoulis, George] McGill Univ, Res Inst, Ctr Hlth, Montreal, PQ, Canada.
[Hwang, Shih-Jen; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Framingham, MA USA.
[Thanassoulis, George; Peloso, Gina M.; Hwang, Shih-Jen; Cupples, L. Adrienne; Kathiresan, Sekar; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Peloso, Gina M.; Malhotra, Rajeev; Kathiresan, Sekar; O'Donnell, Christopher J.] Boston Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02118 USA.
[Campbell, Catherine Y.; Post, Wendy S.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Budoff, Matthew J.] Harbor UCLA, Los Angeles Biomed Res Inst, Los Angeles, CA USA.
[Liu, Yongmei] Wake Forest Sch Med, Winston Salem, NC USA.
[Kerr, Kathleen F.; Wong, Quenna] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[Heckbert, Susan R.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Allison, Matthew A.; Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Owens, David S.; O'Brien, Kevin D.] Univ Washington, Dept Med, Seattle, WA USA.
[Smith, Albert V.; Aspelund, Thor; Sigurdsson, Sigurdur; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Harris, Tamara B.] NIA, Bethesda, MD 20892 USA.
[Caslake, Muriel] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Di Angelantonio, Emanuele; Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Smith, J. Gustav] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Smith, J. Gustav; van der Pals, Jesper] Lund Univ, Dept Cardiol, Lund, Sweden.
[Sjogren, Marketa; Melander, Olle] Lund Univ, Dept Clin Sci, Malmo, Sweden.
[Pechlivanis, Sonali] Univ Essen Gesamthsch, Inst Med Informat Biometry & Epidemiol, Essen, Germany.
[Kaelsch, Hagen; Erbel, Raimund] W German Heart Ctr, Dept Cardiol, Essen, Germany.
[Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany.
[Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Noethen, Markus M.] Univ Bonn, German Ctr Neurodegenerat Dis, Bonn, Germany.
[Kamstrup, Pia R.; Tybjaerg-Hansen, Anne] Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark.
[Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Copenhagen, Denmark.
[Nordestgaard, Borge G.; Tybjaerg-Hansen, Anne] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark.
RP Post, WS (reprint author), Carnegie 568,600 N Wolfe St, Baltimore, MD 21287 USA.
EM wpost@jhmi.edu
RI Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015; Smith,
Albert/K-5150-2015; Kerr, Kathleen/A-2893-2013;
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084; Smith, Albert/0000-0003-1942-5845;
Cupples, L. Adrienne/0000-0003-0273-7965; Di Angelantonio,
Emanuele/0000-0001-8776-6719; Owens, David/0000-0002-7293-9688; Nothen,
Markus/0000-0002-8770-2464; Allison, Matthew/0000-0003-0777-8272
FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-25195,
N02-HL-6-4278, N01-HC-95159, 95169, RR-024156, R01-HL-071739,
R01-HL-071051, R01-HL-071205, R01-HL-071250, R01-HL-071251,
R01-HL-071252, R01-HL-071258, R01-HL-071259, N01-HC-65226]; Affymetrix
for genotyping services; National Institute on Aging [N01-AG-12100];
National Eye Institute; National Institute on Deafness and Other
Communication Disorders; National Institute on Aging Intramural Research
Program, Hjartavernd (the Icelandic Heart Association); Althingi
(Icelandic parliament); MESA; MESA Family; MESA CARe; MESA SHARe
project; Heinz Nixdorf Recall Study; Heinz Nixdorf Foundation; German
Foundation of Research (DFG); Malmo Diet and Cancer study; Swedish
Cancer Society; Swedish Medical Research Council; Swedish Dairy
Association; Albert Pahlsson Foundation; Gunnar Nilsson Foundation;
Malmo city council; Copenhagen City Heart Study; Danish Heart Foundation
FX The Framingham Heart Study was supported by a grant (N01-HC-25195) from
the National Heart, Lung, and Blood Institute (NHLBI) and an NHLBI
contract (N02-HL-6-4278) with Affymetrix for genotyping services; the
Age, Gene/Environment Susceptibility-Reykjavik Study, by a grant from
the National Institute on Aging (N01-AG-12100) and by the National Eye
Institute, the National Institute on Deafness and Other Communication
Disorders, the NHLBI, the National Institute on Aging Intramural
Research Program, Hjartavernd (the Icelandic Heart Association), and the
Althingi (Icelandic parliament); the MESA, MESA Family, MESA CARe, and
the MESA SHARe project, by grants (N01-HC-95159 through 95169,
RR-024156, R01-HL-071739, R01-HL-071051, R01-HL-071205, R01-HL-071250,
R01-HL-071251, R01-HL-071252, R01-HL-071258, R01-HL-071259,
N02-HL-6-4278, and N01-HC-65226) from the NHLBI; the Heinz Nixdorf
Recall Study, by the Heinz Nixdorf Foundation and the German Foundation
of Research (DFG); the Malmo Diet and Cancer study, by the Swedish
Cancer Society, the Swedish Medical Research Council, the Swedish Dairy
Association, the Albert Pahlsson and Gunnar Nilsson Foundations, and the
Malmo city council; and the Copenhagen City Heart Study, by the Danish
Heart Foundation. Detailed information on support for individual authors
and analyses is available in the Supplementary Appendix.
NR 47
TC 164
Z9 170
U1 3
U2 31
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 FEB 7
PY 2013
VL 368
IS 6
BP 503
EP 512
DI 10.1056/NEJMoa1109034
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 083VU
UT WOS:000314494100001
PM 23388002
ER
PT J
AU Nabel, GJ
AF Nabel, Gary J.
TI GLOBAL HEALTH Designing Tomorrow's Vaccines
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID BROADLY NEUTRALIZING ANTIBODIES; CELLULAR-IMMUNITY; INFLUENZA VACCINE;
RATIONAL DESIGN; CLINICAL-TRIALS; VIRUS-VACCINES; SIV INFECTION; HIV
VACCINE; POTENT; PROTECTION
C1 [Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Nabel, GJ (reprint author), Sanofi, 640 Mem Dr, Cambridge, MA 02139 USA.
EM gary.nabel@sanofi.com
RI Chiang, Vincent, Ming-Hsien/D-4312-2016
OI Chiang, Vincent, Ming-Hsien/0000-0002-2029-7863
FU Intramural NIH HHS [Z01 AI005002-06, Z99 AI999999, ZIA AI005002-08, ZIA
AI005003-08, ZIA AI005058-07, Z01 AI005003-06]
NR 52
TC 77
Z9 78
U1 2
U2 46
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 FEB 7
PY 2013
VL 368
IS 6
BP 551
EP 560
DI 10.1056/NEJMra1204186
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 083VU
UT WOS:000314494100006
PM 23388006
ER
PT J
AU Zarin, DA
Tse, T
AF Zarin, Deborah A.
Tse, Tony
TI Unambiguous Identification of Obesity Trials
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Zarin, Deborah A.; Tse, Tony] Natl Lib Med, Bethesda, MD USA.
RP Zarin, DA (reprint author), Natl Lib Med, Bethesda, MD USA.
EM dzarin@mail.nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 2
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 FEB 7
PY 2013
VL 368
IS 6
BP 580
EP 581
DI 10.1056/NEJMc1215018
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 083VU
UT WOS:000314494100025
PM 23388022
ER
PT J
AU Klase, ZA
Sampey, GC
Kashanchi, F
AF Klase, Zachary A.
Sampey, Gavin C.
Kashanchi, Fatah
TI Retrovirus infected cells contain viral microRNAs
SO RETROVIROLOGY
LA English
DT Editorial Material
DE Retrovirus; microRNA; Bovine leukemia virus; Human immunodeficiency
virus; West nile virus; Transcriptional gene silencing; RNA polymerase
III
ID SMALL NONCODING RNAS; HIV-1-INFECTED CELLS; INTERFERENCE; REPLICATION
AB The encoding of microRNAs in retroviral genomes has remained a controversial hypothesis despite significant supporting evidence in recent years. A recent publication demonstrating the production of functional miRNAs from the retrovirus bovine leukemia virus adds further credence to the fact that retroviruses do indeed encode their own miRNAs. Here we comment on the importance of this paper to the field, as well as examine the other known examples of miRNAs encoded by RNA viruses.
C1 [Klase, Zachary A.] NIAID, Mol Virol Sect, Mol Microbiol Lab, Bethesda, MD 20810 USA.
[Sampey, Gavin C.; Kashanchi, Fatah] George Mason Univ, Natl Ctr Biodef & Infect Dis, Sch Syst Biol, Manassas, VA 20108 USA.
RP Kashanchi, F (reprint author), George Mason Univ, Natl Ctr Biodef & Infect Dis, Sch Syst Biol, 10900 Univ Blvd, Manassas, VA 20108 USA.
EM fkashanc@gmu.edu
FU NIAID NIH HHS [AI074410, AI078859]
NR 15
TC 8
Z9 8
U1 0
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD FEB 7
PY 2013
VL 10
AR 15
DI 10.1186/1742-4690-10-15
PG 4
WC Virology
SC Virology
GA 088JZ
UT WOS:000314831600001
PM 23391025
ER
PT J
AU Mehta, B
Snellman, J
Chen, S
Li, W
Zenisek, D
AF Mehta, Bhupesh
Snellman, Josefin
Chen, Shan
Li, Wei
Zenisek, David
TI Synaptic Ribbons Influence the Size and Frequency of Miniature-like
Evoked Postsynaptic Currents
SO NEURON
LA English
DT Article
ID MULTIVESICULAR RELEASE; SPONTANEOUS NEUROTRANSMISSION; TRANSMITTER
RELEASE; BIPOLAR CELLS; MOUSE RETINA; RAT RETINA; SYNAPSES; ROD;
EXOCYTOSIS; LUMINANCE
AB Nonspiking cells of several sensory systems respond to stimuli with graded changes in neurotransmitter release and possess specialized synaptic ribbons. Here, we show that manipulations to synaptic ribbons caused dramatic effects on mEPSC-like (mIEPSC) amplitude and frequency. Damage to rod-bipolar cell ribbons using fluorophore-assisted light inactivation resulted in the immediate reduction of mIEPSC amplitude and frequency, whereas the first evoked response after damage remained largely intact. The reduction in amplitude could not be recovered by increasing release frequency after ribbon damage. In parallel experiments, we looked at mIEPSCs from cones of hibernating ground squirrels, which exhibit dramatically smaller ribbons than awake animals. Fewer and smaller mIEPSCs were observed postsynaptic to cones from hibernating animals, although depolarized cones were able to generate larger mIEPSCs. Our results indicate that ribbon size may influence mIEPSC frequency and support a role for ribbons in coordinating multivesicular release.
C1 [Mehta, Bhupesh; Snellman, Josefin; Zenisek, David] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA.
[Zenisek, David] Yale Univ, Sch Med, Dept Ophthalmol & Visual Sci, New Haven, CT 06520 USA.
[Zenisek, David] Yale Univ, Sch Med, Program Cellular Neurosci Neurodegenerat & Repair, New Haven, CT 06520 USA.
[Chen, Shan; Li, Wei] NEI, Unit Retinal Neurophysiol, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Li, W (reprint author), NEI, Unit Retinal Neurophysiol, Intramural Res Program, NIH, 35 Convent Dr,Room 2A-108, Bethesda, MD 20892 USA.
EM liwei2@nei.nih.gov; david.zenisek@yale.edu
FU National Institutes of Health [EY014990]; National Eye Institute
Intramural Research Program
FX This work was funded by the National Institutes of Health (grant no.
EY014990, to D.Z.) and the National Eye Institute Intramural Research
Program (W.L.).
NR 47
TC 15
Z9 16
U1 0
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD FEB 6
PY 2013
VL 77
IS 3
BP 516
EP 527
DI 10.1016/j.neuron.2012.11.024
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 118MY
UT WOS:000317030800013
PM 23395377
ER
PT J
AU Alemayehu, M
Dragan, M
Pape, C
Siddiqui, I
Sacks, DB
Di Guglielmo, GM
Babwah, AV
Bhattacharya, M
AF Alemayehu, Mistre
Dragan, Magdalena
Pape, Cynthia
Siddiqui, Iram
Sacks, David B.
Di Guglielmo, Gianni M.
Babwah, Andy V.
Bhattacharya, Moshmi
TI beta-Arrestin2 Regulates Lysophosphatidic Acid-Induced Human Breast
Tumor Cell Migration and Invasion via Rap1 and IQGAP1
SO PLOS ONE
LA English
DT Article
ID STRESS FIBER FORMATION; BETA-ARRESTIN; CANCER METASTASIS;
EPITHELIAL-CELLS; PROSTATE-CANCER; LEADING-EDGE; ACTIVATION; RECEPTOR;
PROTEINS; ADHESION
AB beta-arrestins play critical roles in chemotaxis and cytoskeletal reorganization downstream of several receptor types, including G protein-coupled receptors (GPCRs), which are targets for greater than 50% of all pharmaceuticals. Among them, receptors for lysophosphatidic acid (LPA), namely LPA(1) are overexpressed in breast cancer and promote metastatic spread. We have recently reported that beta-arrestin2 regulates LPA(1)-mediated breast cancer cell migration and invasion, although the underlying molecular mechanisms are not clearly understood. We show here that LPA induces activity of the small G protein, Rap1 in breast cancer cells in a beta-arrestin2-dependent manner, but fails to activate Rap1 in non-malignant mammary epithelial cells. We found that Rap1A mRNA levels are higher in human breast tumors compared to healthy patient samples and Rap1A is robustly expressed in human ductal carcinoma in situ and invasive tumors, in contrast to the normal mammary ducts. Rap1A protein expression is also higher in aggressive breast cancer cells (MDA-MB-231 and Hs578t) relative to the weakly invasive MCF-7 cells or non-malignant MCF10A mammary cells. Depletion of Rap1A expression significantly impaired LPA-stimulated migration of breast cancer cells and invasiveness in three-dimensional Matrigel cultures. Furthermore, we found that beta-arrestin2 associates with the actin binding protein IQGAP1 in breast cancer cells, and is necessary for the recruitment of IQGAP1 to the leading edge of migratory cells. Depletion of IQGAP1 blocked LPA-stimulated breast cancer cell invasion. Finally, we have identified that LPA enhances the binding of endogenous Rap1A to beta-arrestin2, and also stimulates Rap1A and IQGAP1 to associate with LPA1. Thus our data establish novel roles for Rap1A and IQGAP1 as critical regulators of LPA-induced breast cancer cell migration and invasion.
C1 [Alemayehu, Mistre; Dragan, Magdalena; Pape, Cynthia; Di Guglielmo, Gianni M.; Babwah, Andy V.; Bhattacharya, Moshmi] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON, Canada.
[Siddiqui, Iram] Univ Western Ontario, Dept Pathol, London, ON, Canada.
[Babwah, Andy V.] Univ Western Ontario, Childrens Hlth Res Inst, London, ON, Canada.
[Babwah, Andy V.] Univ Western Ontario, Lawson Hlth Res Inst, London, ON, Canada.
[Babwah, Andy V.] Univ Western Ontario, Dept Obstet & Gynecol, London, ON, Canada.
[Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
RP Bhattacharya, M (reprint author), Univ Western Ontario, Dept Physiol & Pharmacol, London, ON, Canada.
EM moshmi.bhattacharya@schulich.uwo.ca
FU Canadian Institutes of Health Research (CIHR) [MOP 107972]; National
Institutes of Health; CIHR Strategic Training Program/Translational
Breast Cancer Research Unit
FX This study was supported by a grant awarded to MB by the Canadian
Institutes of Health Research (CIHR) MOP 107972. DS is supported by the
Intramural Research Program of the National Institutes of Health. The
following are recipients of salary awards and studentships: MB and AB,
CIHR Canadian Institute of Health Research New Investigator Awards; MA,
CIHR Strategic Training Program/Translational Breast Cancer Research
Unit studentships. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 62
TC 15
Z9 17
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 FEB 6
PY 2013
VL 8
IS 2
AR e56174
DI 10.1371/journal.pone.0056174
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092WJ
UT WOS:000315153400210
PM 23405264
ER
PT J
AU Cahoon, EK
Wheeler, DC
Kimlin, MG
Kwok, RK
Alexander, BH
Little, MP
Linet, MS
Freedman, DM
AF Cahoon, Elizabeth Khaykin
Wheeler, David C.
Kimlin, Michael G.
Kwok, Richard K.
Alexander, Bruce H.
Little, Mark P.
Linet, Martha S.
Freedman, Daryl Michal
TI Individual, Environmental, and Meteorological Predictors of Daily
Personal Ultraviolet Radiation Exposure Measurements in a United States
Cohort Study
SO PLOS ONE
LA English
DT Article
ID CANCER-MORTALITY RATES; SUN EXPOSURE; VITAMIN-D; RADIOLOGIC
TECHNOLOGISTS; MEASUREMENT ERROR; OCULAR MELANOMA; SKIN; RISK;
REPRODUCIBILITY; POPULATION
AB Background: Individual exposure to ultraviolet radiation (UVR) is challenging to measure, particularly for diseases with substantial latency periods between first exposure and diagnosis of outcome, such as cancer. To guide the choice of surrogates for long-term UVR exposure in epidemiologic studies, we assessed how well stable sun-related individual characteristics and environmental/meteorological factors predicted daily personal UVR exposure measurements.
Methods: We evaluated 123 United States Radiologic Technologists subjects who wore personal UVR dosimeters for 8 hours daily for up to 7 days (N = 837 days). Potential predictors of personal UVR derived from a self-administered questionnaire, and public databases that provided daily estimates of ambient UVR and weather conditions. Factors potentially related to personal UVR exposure were tested individually and in a model including all significant variables.
Results: The strongest predictors of daily personal UVR exposure in the full model were ambient UVR, latitude, daily rainfall, and skin reaction to prolonged sunlight (R-2 = 0.30). In a model containing only environmental and meteorological variables, ambient UVR, latitude, and daily rainfall were the strongest predictors of daily personal UVR exposure (R-2 = 0.25).
Conclusions: In the absence of feasible measures of individual longitudinal sun exposure history, stable personal characteristics, ambient UVR, and weather parameters may help estimate long-term personal UVR exposure.
C1 [Cahoon, Elizabeth Khaykin; Little, Mark P.; Linet, Martha S.; Freedman, Daryl Michal] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Wheeler, David C.] Virginia Commonwealth Univ, Sch Med, Dept Biostat, Richmond, VA USA.
[Kimlin, Michael G.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, AusSun Res Lab, Brisbane, Qld 4001, Australia.
[Kwok, Richard K.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Alexander, Bruce H.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA.
RP Cahoon, EK (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM khaykine@mail.nih.gov
RI Kwok, Richard/B-6907-2017;
OI Kwok, Richard/0000-0002-6794-8360; Kimlin, Michael/0000-0002-9536-8646;
Little, Mark/0000-0003-0980-7567
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health, Department of Health and Human Services
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health, Department of
Health and Human Services. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 44
TC 6
Z9 6
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 FEB 6
PY 2013
VL 8
IS 2
AR e54983
DI 10.1371/journal.pone.0054983
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092WJ
UT WOS:000315153400046
PM 23405102
ER
PT J
AU Goldenberg, DM
Gold, DV
Loo, M
Liu, DL
Chang, CH
Jaffe, ES
AF Goldenberg, David M.
Gold, David V.
Loo, Meiyu
Liu, Donglin
Chang, Chien-Hsing
Jaffe, Elaine S.
TI Horizontal Transmission of Malignancy: In-Vivo Fusion of Human Lymphomas
with Hamster Stroma Produces Tumors Retaining Human Genes and Lymphoid
Pathology
SO PLOS ONE
LA English
DT Article
ID REED-STERNBERG CELLS; HODGKINS-DISEASE; NUDE-MICE; B-CELL; METASTATIC
PHENOTYPE; HOST-CELLS; CANCER; TRANSFORMATION; CHROMOSOME; BIOLOGY
AB We report the in-vivo fusion of two Hodgkin lymphomas with golden hamster cheek pouch cells, resulting in serially transplanted (over 5-6 years) GW-532 and GW-584 heterosynkaryon tumor cells displaying both human and hamster DNA (by FISH), lymphoma-like morphology, aggressive metastasis, and retention of 7 human genes (CD74, CXCR4, CD19, CD20, CD71, CD79b, and VIM) out of 24 tested by PCR. The prevalence of B-cell restricted genes (CD19, CD20, and CD79b) suggests that this uniform population may be the clonal initiating (malignant) cells of Hodgkin lymphoma, despite their not showing translation to their respective proteins by immunohistochemical analysis. This is believed to be the first report of in-vivo cell-cell fusion of human lymphoma and rodent host cells, and may be a method to disclose genes regulating both organoid and metastasis signatures, suggesting that the horizontal transfer of tumor DNA to adjacent stromal cells may be implicated in tumor heterogeneity and progression. The B-cell gene signature of the hybrid xenografts suggests that Hodgkin lymphoma, or its initiating cells, is a B-cell malignancy.
C1 [Goldenberg, David M.; Gold, David V.] Garden State Canc Ctr, Ctr Mol Med & Immunol, Morris Plains, NJ USA.
[Loo, Meiyu; Liu, Donglin; Chang, Chien-Hsing] Immunomedics Inc, Morris Plains, NJ USA.
[Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Goldenberg, DM (reprint author), Garden State Canc Ctr, Ctr Mol Med & Immunol, Morris Plains, NJ USA.
EM dmg.gscancer@att.net
OI Jaffe, Elaine/0000-0003-4632-0301
FU National Cancer Institute, National Institutes of Health; National
Institutes of Health [CA11327]
FX This work was supported in part by the intramural research program of
the National Cancer Institute, National Institutes of Health (ESJ), and
USPHS grant CA11327 from the National Institutes of Health (DMG) for
establishing the original GW-532 and GW-584 tumors. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 49
TC 10
Z9 13
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 FEB 6
PY 2013
VL 8
IS 2
AR e55324
DI 10.1371/journal.pone.0055324
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092WJ
UT WOS:000315153400080
PM 23405135
ER
PT J
AU Page, S
Birerdinc, A
Estep, M
Stepanova, M
Afendy, A
Petricoin, E
Younossi, Z
Chandhoke, V
Baranova, A
AF Page, Sandra
Birerdinc, Aybike
Estep, Michael
Stepanova, Maria
Afendy, Arian
Petricoin, Emanuel
Younossi, Zobair
Chandhoke, Vikas
Baranova, Ancha
TI Knowledge-Based Identification of Soluble Biomarkers: Hepatic Fibrosis
in NAFLD as an Example
SO PLOS ONE
LA English
DT Article
ID FATTY LIVER-DISEASE; NONALCOHOLIC STEATOHEPATITIS; METABOLIC SYNDROME;
FAS LIGAND; ADIPOKINES; DISCOVERY; CIRRHOSIS
AB The discovery of biomarkers is often performed using high-throughput proteomics-based platforms and is limited to the molecules recognized by a given set of purified and validated antigens or antibodies. Knowledge-based, or systems biology, approaches that involve the analysis of integrated data, predominantly molecular pathways and networks may infer quantitative changes in the levels of biomolecules not included by the given assay from the levels of the analytes profiled. In this study we attempted to use a knowledge-based approach to predict biomarkers reflecting the changes in underlying protein phosphorylation events using Nonalcoholic Fatty Liver Disease (NAFLD) as a model. Two soluble biomarkers, CCL-2 and FasL, were inferred in silico as relevant to NAFLD pathogenesis. Predictive performance of these biomarkers was studied using serum samples collected from patients with histologically proven NAFLD. Serum levels of both molecules, in combination with clinical and demographic data, were predictive of hepatic fibrosis in a cohort of NAFLD patients. Our study suggests that (1) NASH-specific disruption of the kinase-driven signaling cascades in visceral adipose tissue lead to detectable changes in the levels of soluble molecules released into the bloodstream, and (2) biomarkers discovered in silico could contribute to predictive models for non-malignant chronic diseases.
C1 [Page, Sandra; Birerdinc, Aybike; Stepanova, Maria; Petricoin, Emanuel; Chandhoke, Vikas; Baranova, Ancha] George Mason Univ, Coll Sci, Sch Syst Biol, Ctr Study Chron Metab Dis, Fairfax, VA 22030 USA.
[Page, Sandra; Birerdinc, Aybike; Estep, Michael; Stepanova, Maria; Afendy, Arian; Younossi, Zobair; Baranova, Ancha] Inova Hlth Syst, Betty & Guy Beatty Liver & Obes Program, Falls Church, VA USA.
[Estep, Michael; Afendy, Arian; Younossi, Zobair] Inova Fairfax Hosp, Ctr Liver Dis, Falls Church, VA USA.
[Estep, Michael; Afendy, Arian; Younossi, Zobair] Inova Fairfax Hosp, Dept Med, Falls Church, VA USA.
[Petricoin, Emanuel] George Mason Univ, Coll Sci, Sch Syst Biol, Ctr Appl Prote & Mol Med, Fairfax, VA 22030 USA.
[Baranova, Ancha] Res Ctr Med Genet RAMS, Moscow, Russia.
[Page, Sandra] NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Baranova, A (reprint author), George Mason Univ, Coll Sci, Sch Syst Biol, Ctr Study Chron Metab Dis, Fairfax, VA 22030 USA.
EM abaranov@gmu.edu
OI Estep, J. Michael/0000-0001-7735-2133
NR 20
TC 8
Z9 8
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 FEB 6
PY 2013
VL 8
IS 2
AR e56009
DI 10.1371/journal.pone.0056009
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092WJ
UT WOS:000315153400189
PM 23405244
ER
PT J
AU Christian, BT
Wooten, DW
Hillmer, AT
Tudorascu, DL
Converse, AK
Moore, CF
Ahlers, EO
Barnhart, TE
Kalin, NH
Barr, CS
Schneider, ML
AF Christian, Bradley T.
Wooten, Dustin W.
Hillmer, Ansel T.
Tudorascu, Dana L.
Converse, Alexander K.
Moore, Colleen F.
Ahlers, Elizabeth O.
Barnhart, Todd E.
Kalin, Ned H.
Barr, Christina S.
Schneider, Mary L.
TI Serotonin Transporter Genotype Affects Serotonin 5-HT1A Binding in
Primates
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; GENE VARIATION; HUMAN BRAIN; FUNCTIONAL
POLYMORPHISM; REARING CONDITION; RECEPTOR-BINDING; NONHUMAN PRIMATE;
PROMOTER REGION; RHESUS-MONKEYS; STRESS
AB Disruption of the serotonin system has been implicated in anxiety and depression and a related genetic variation has been identified that may predispose individuals for these illnesses. The relationship of a functional variation of the serotonin transporter promoter gene (5-HTTLPR) on serotonin transporter binding using in vivo imaging techniques have yielded inconsistent findings when comparing variants for short (s) and long (l) alleles. However, a significant 5-HTTLPR effect on receptor binding at the 5-HT1A receptor site has been reported in humans, suggesting the 5-HTTLPR polymorphism may play a role in serotonin (5-HT) function. Rhesus monkeys possess a 5-HTTLPR length polymorphism similar to humans and serve as an excellent model for studying the effects of this orthologous genetic variation on behaviors and neurochemical functions related to the 5-HT system. In this study, PET imaging of [F-18]mefway was performed on 58 rhesus monkeys (33 l/l, 25 s-carriers) to examine the relation between 5-HT1A receptor-specific binding and 5-HTTLPR genotypes. Significantly lower 5-HT1A binding was found in s-carrier subjects throughout both cortical brain regions and the raphe nuclei. These results demonstrate that the underlying 5-HT neurochemical system is influenced by this functional polymorphism and illustrate the strong potential for extending the nonhuman primate model into investigating the role of this genetic variant on behavior and gene-environment interactions.
C1 [Christian, Bradley T.; Wooten, Dustin W.; Hillmer, Ansel T.; Barnhart, Todd E.] Univ Wisconsin, Dept Med Phys, Madison, WI 53705 USA.
[Schneider, Mary L.] Univ Wisconsin, Dept Kinesiol, Madison, WI 53705 USA.
[Christian, Bradley T.; Kalin, Ned H.] Univ Wisconsin, Dept Psychiat, Madison, WI 53705 USA.
[Moore, Colleen F.; Kalin, Ned H.; Schneider, Mary L.] Univ Wisconsin, Dept Psychol, Madison, WI 53705 USA.
[Christian, Bradley T.; Converse, Alexander K.; Ahlers, Elizabeth O.; Kalin, Ned H.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA.
[Tudorascu, Dana L.] Univ Pittsburgh, Dept Med & Biostat, Pittsburgh, PA 15312 USA.
[Barr, Christina S.] NIAAA, NIH, Bethesda, MD 20892 USA.
RP Christian, BT (reprint author), Univ Wisconsin, Waisman Ctr, Brain Imaging Lab, 1500 Highland Ave, Madison, WI 53705 USA.
EM bchristian@wisc.edu
OI Barnhart, Todd/0000-0002-9981-2150
FU NIH [AA017706, MH086014, AA12277, AA10079, T32CA009206, S10RR015801,
P30HD003352, S10RR023033]
FX This work was supported by NIH Grants AA017706, MH086014, AA12277,
AA10079, and T32CA009206. Additional support was provided by NIH Grants
S10RR015801, P30HD003352, and S10RR023033. We thank the following for
their contribution to this research: Professor R. Jerry Nickles and Dr.
Jonathan Engle for assistance with isotope production; Maxim Slesarev
and Julie Larson and the staff at the Harlow Center for Biological
Psychology at the University of Wisconsin for nonhuman primate handling;
Andrew Higgins for data processing; and Professor Jim Holden and
Professor Jogesh Mukherjee (University of California, Irvine) for
technical discussions.
NR 35
TC 12
Z9 12
U1 6
U2 17
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 FEB 6
PY 2013
VL 33
IS 6
BP 2512
EP 2516
DI 10.1523/JNEUROSCI.4182-12.2013
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 088CS
UT WOS:000314812000025
PM 23392679
ER
PT J
AU Camprubi-Robles, M
Mair, N
Andratsch, M
Benetti, C
Beroukas, D
Rukwied, R
Langeslag, M
Proia, RL
Schmelz, M
Montiel, AVF
Haberberger, RV
Kress, M
AF Camprubi-Robles, Maria
Mair, Norbert
Andratsch, Manfred
Benetti, Camilla
Beroukas, Dimitra
Rukwied, Roman
Langeslag, Michiel
Proia, Richard L.
Schmelz, Martin
Ferrer Montiel, Antonio V.
Haberberger, Rainer V.
Kress, Michaela
TI Sphingosine-1-Phosphate-Induced Nociceptor Excitation and Ongoing Pain
Behavior in Mice and Humans Is Largely Mediated by S1P3 Receptor
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID RAT SENSORY NEURONS; SPHINGOSINE 1-PHOSPHATE RECEPTOR; ROOT GANGLION
NEURONS; INFLAMMATORY MEDIATORS; ENDOTHELIAL-CELLS; HUMAN PLATELETS;
ACTIVATION; PLASMA; KINASE; ROLES
AB The biolipid sphingosine-1-phosphate (S1P) is an essential modulator of innate immunity, cell migration, and wound healing. It is released locally upon acute tissue injury from endothelial cells and activated thrombocytes and, therefore, may give rise to acute post-traumatic pain sensation via a yet elusive molecular mechanism. We have used an interdisciplinary approach to address this question, and we find that intradermal injection of S1P induced significant licking and flinching behavior in wild-type mice and a dose-dependent flare reaction in human skin as a sign of acute activation of nociceptive nerve terminals. Notably, S1P evoked a small excitatory ionic current that resulted in nociceptor depolarization and action potential firing. This ionic current was preserved in "cation-free" solution and blocked by the nonspecific Cl- channel inhibitor niflumic acid and by preincubation with the G-protein inhibitor GDP-beta-S. Notably, S1P(3) receptor was detected in virtually all neurons in human and mouse DRG. In line with this finding, S1P-induced neuronal responses and spontaneous pain behavior in vivo were substantially reduced in S1P(3)(-/-) mice, whereas in control S1P(1) floxed (S1P(1)(fl/fl)) mice and mice with a nociceptor-specific deletion of S1P(1)(-/-) receptor (SNS-S1P(1)(-/-)), neither the S1P-induced responses in vitro nor the S1P-evoked pain-like behavior was altered. Therefore, these findings indicate that S1P evokes significant nociception via G-protein-dependent activation of an excitatory Cl- conductance that is largely mediated by S1P(3) receptors present in nociceptors, and point to these receptors as valuable therapeutic targets for post-traumatic pain.
C1 [Camprubi-Robles, Maria; Mair, Norbert; Andratsch, Manfred; Benetti, Camilla; Langeslag, Michiel; Kress, Michaela] Med Univ Innsbruck, Dept Physiol & Med Phys, Div Physiol, A-6020 Innsbruck, Austria.
[Camprubi-Robles, Maria; Ferrer Montiel, Antonio V.] Miguel Hernandez Univ, Inst Mol & Cellular Biol, Alicante 03202, Spain.
[Beroukas, Dimitra; Haberberger, Rainer V.] Flinders Univ S Australia, Dept Anat & Histol, Bedford Pk, SA 5042, Australia.
[Beroukas, Dimitra; Haberberger, Rainer V.] Flinders Univ S Australia, Ctr Neurosci, Bedford Pk, SA 5042, Australia.
[Rukwied, Roman; Schmelz, Martin] Heidelberg Univ, Dept Anaesthesiol & Intens Care Med, Med Fac Mannheim, D-68167 Mannheim, Germany.
[Proia, Richard L.] NIDDK, Bethesda, MD 20892 USA.
RP Camprubi-Robles, M (reprint author), Miguel Hernandez Univ, Inst Mol & Cellular Biol, Avda Univ S-N, Alicante 03202, Spain.
EM mcamprubi@umh.es; michaela.kress@i-med.ac.at
RI Ferrer-Montiel, Antonio/C-3072-2015;
OI Ferrer-Montiel, Antonio/0000-0002-2973-6607; Schmelz,
Martin/0000-0002-9736-7241; Haberberger, Rainer
Viktor/0000-0001-8043-3786
FU la Generalitat Valenciana; Ministerio de Economia y Competitividad;
Australian National Health and Medical Research Council [535055];
National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases; Austrian Research Funding Agency FWF
Project [P20562, P25345, SPIN]
FX The authors thank K. Braun, T. Martha, and M. Doblander for expert
technical assistance. This work was supported by la Generalitat
Valenciana and the Ministerio de Economia y Competitividad (A.V.F.M.),
the Australian National Health and Medical Research Council Project
Grant 535055 to R.V.H., the Intramural Research Programs of the National
Institutes of Health, National Institute of Diabetes and Digestive and
Kidney Diseases to R.L.P., and the Austrian Research Funding Agency FWF
Project Grants P20562, P25345, and SPIN to M.K.
NR 63
TC 15
Z9 15
U1 1
U2 12
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 FEB 6
PY 2013
VL 33
IS 6
BP 2582
EP 2592
DI 10.1523/JNEUROSCI.4479-12.2013
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 088CS
UT WOS:000314812000032
PM 23392686
ER
PT J
AU Rao, TSC
Saha, S
Raolji, GB
Patro, B
Risbood, P
Difilippantonio, MJ
Tomaszewski, JE
Malhotra, SV
AF Rao, T. S. Chinta
Saha, Sanjay
Raolji, Gajendra B.
Patro, Balaram
Risbood, Prabhaker
Difilippantonio, Michael J.
Tomaszewski, Joseph E.
Malhotra, Sanjay V.
TI Microwave assisted Westphal condensation and its application to
synthesis of sempervirine and related compounds
SO TETRAHEDRON LETTERS
LA English
DT Article
DE Sempervirine; Westphal condensation; Microwave assisted; DNA
intercalator; Antiproliferative agent
ID ZWITTERIONIC INDOLE ALKALOIDS; DIRECTED METALATION ROUTE; CANCER-CELLS;
DIHYDROFLAVOPEREIRINE; SALTS; MDM2; P53
AB A concise synthesis of a potent lead in anticancer therapeutics, sempervirine, was achieved by one pot Westphal condensation, ester hydrolysis, and decarboxylation under microwave irradiation. The method was extended to the synthesis of several similar heterocycles. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Rao, T. S. Chinta; Saha, Sanjay; Raolji, Gajendra B.; Patro, Balaram] GVK Biosci Pvt Ltd, Div Med Chem, Hyderabad, Andhra Pradesh, India.
[Rao, T. S. Chinta; Saha, Sanjay] JNT Univ, Dept Chem, Hyderabad, Andhra Pradesh, India.
[Risbood, Prabhaker; Difilippantonio, Michael J.; Tomaszewski, Joseph E.] NCI, Div Canc Treatment & Diagnosis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Malhotra, Sanjay V.] SAIC Frederick Inc, Lab Synthet Chem, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Patro, B (reprint author), GVK Biosci Pvt Ltd, Div Med Chem, Hyderabad, Andhra Pradesh, India.
EM balaram.patro@gvkbio.com; malhotrasa@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; GVK Biosciences Private Limited
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.
T.S.C.R., S.S., B.P,. and G.B.R. sincerely thank GVK Biosciences Private
Limited for financial support and encouragement. Support from analytical
department is also acknowledged.
NR 24
TC 3
Z9 3
U1 2
U2 17
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0040-4039
J9 TETRAHEDRON LETT
JI Tetrahedron Lett.
PD FEB 6
PY 2013
VL 54
IS 6
BP 487
EP 490
DI 10.1016/j.tetlet.2012.11.059
PG 4
WC Chemistry, Organic
SC Chemistry
GA 082JO
UT WOS:000314388300010
ER
PT J
AU Brown, VL
Drake, JM
Stallknecht, DE
Brown, JD
Pedersen, K
Rohani, P
AF Brown, V. L.
Drake, J. M.
Stallknecht, D. E.
Brown, J. D.
Pedersen, K.
Rohani, P.
TI Dissecting a wildlife disease hotspot: the impact of multiple host
species, environmental transmission and seasonality in migration,
breeding and mortality
SO JOURNAL OF THE ROYAL SOCIETY INTERFACE
LA English
DT Article
DE avian influenza; multi-host mathematical model; environmental
transmission; disease hotspot
ID AVIAN INFLUENZA-VIRUS; DELAWARE BAY; A VIRUS; BIRDS; WATER; INFECTION;
DYNAMICS; DUCKS; SURVEILLANCE; TEMPERATURE
AB Avian influenza viruses (AIVs) have been implicated in all human influenza pandemics in recent history. Despite this, surprisingly little is known about the mechanisms underlying the maintenance and spread of these viruses in their natural bird reservoirs. Surveillance has identified an AIV 'hotspot' in shorebirds at Delaware Bay, in which prevalence is estimated to exceed other monitored sites by an order of magnitude. To better understand the factors that create an AIV hotspot, we developed and parametrized a mechanistic transmission model to study the simultaneous epizootiological impacts of multi-species transmission, seasonal breeding, host migration and mixed transmission routes. We scrutinized our model to examine the potential for an AIV hotspot to serve as a 'gateway' for the spread of novel viruses into North America. Our findings identify the conditions under which a novel influenza virus, if introduced into the system, could successfully invade and proliferate.
C1 [Brown, V. L.; Rohani, P.] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Brown, V. L.; Rohani, P.] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
[Drake, J. M.] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA.
[Stallknecht, D. E.; Brown, J. D.] Univ Georgia, SE Cooperat Wildlife Dis Study, Athens, GA 30602 USA.
[Pedersen, K.] Anim & Plant Hlth Inspect Serv, USDA, Wildlife Serv, Natl Wildlife Dis Program, Ft Collins, CO 80521 USA.
[Rohani, P.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Brown, VL (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
EM vlbrown@umich.edu
RI Drake, John/D-6622-2012;
OI Drake, John/0000-0003-4646-1235
FU James S. McDonnell Foundation; National Science Foundation
[DEB-0917853]; RAPIDD program of the Science and Technology Directorate,
Department of Homeland Security; Fogarty International Center, National
Institutes of Health; National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Department of Health and Human
Services [HHSN266200700007C]
FX This work was supported by the James S. McDonnell Foundation and the
National Science Foundation (DEB-0917853). P.R. was also supported by
the RAPIDD program of the Science and Technology Directorate, Department
of Homeland Security, and the Fogarty International Center, National
Institutes of Health. D. S. and J.B. were also supported by the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, Department of Health and Human Services, under contract
HHSN266200700007C. Data were collected by numerous biologists from state
and federal agencies participating in the US Early Detection System for
HPAI in wild birds, and made available through the USDA-APHIS Wildlife
Services National Wildlife Disease Program. The opinions expressed
herein are those of the author(s) and do not necessarily reflect the
views of any of the funding agencies.
NR 55
TC 7
Z9 7
U1 0
U2 204
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 1742-5689
J9 J R SOC INTERFACE
JI J. R. Soc. Interface
PD FEB 6
PY 2013
VL 10
IS 79
AR 20120804
DI 10.1098/rsif.2012.0804
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048VB
UT WOS:000311940200009
PM 23173198
ER
PT J
AU White, C
Yuan, XJ
Schmidt, PJ
Bresciani, E
Samuel, TK
Campagna, D
Hall, C
Bishop, K
Calicchio, ML
Lapierre, A
Ward, DM
Liu, P
Fleming, MD
Hamza, I
AF White, Carine
Yuan, Xiaojing
Schmidt, Paul J.
Bresciani, Erica
Samuel, Tamika K.
Campagna, Dean
Hall, Caitlin
Bishop, Kevin
Calicchio, Monica L.
Lapierre, Ariane
Ward, Diane M.
Liu, Paul
Fleming, Mark D.
Hamza, Iqbal
TI HRG1 Is Essential for Heme Transport from the Phagolysosome of
Macrophages during Erythrophagocytosis
SO CELL METABOLISM
LA English
DT Article
ID IRON-METABOLISM; GENE-EXPRESSION; SYSTEM; IDENTIFICATION; OXYGENASE;
MICE; ERYTHROPOIESIS; OVERLOAD; ANEMIA; BACH1
AB Adult humans have about 25 trillion red blood cells (RBCs), and each second we recycle about 5 million RBCs by erythrophagocytosis (EP) in macrophages of the reticuloendothelial system. Despite the central role for EP in mammalian iron metabolism, the molecules and pathways responsible for heme trafficking during EP remain unknown. Here, we show that the mammalian homolog of HRG1, a transmembrane heme permease in C. elegans, is essential for macrophage iron homeostasis and transports heme from the phagolysosome to the cytoplasm during EP. HRG1 is strongly expressed in macrophages of the reticuloendothelial system and specifically localizes to the phagolysosomal membranes during EP. Depletion of Hrg1 in mouse macrophages causes attenuation of heme transport from the phagolysosomal compartment. Importantly, missense polymorphisms in human HRG1 are defective in heme transport. Our results reveal HRG1 as the long-sought heme transporter for heme-iron recycling in macrophages and suggest that genetic variations in HRG1 could be modifiers of human iron metabolism.
C1 [White, Carine; Yuan, Xiaojing; Samuel, Tamika K.; Hall, Caitlin; Hamza, Iqbal] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA.
[White, Carine; Yuan, Xiaojing; Samuel, Tamika K.; Hall, Caitlin; Hamza, Iqbal] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
[Schmidt, Paul J.; Campagna, Dean; Calicchio, Monica L.; Lapierre, Ariane; Fleming, Mark D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pathol, Boston, MA 02115 USA.
[Bresciani, Erica; Liu, Paul] NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA.
[Bishop, Kevin] NHGRI, Zebrafish Core, NIH, Bethesda, MD 20892 USA.
[Ward, Diane M.] Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT 84132 USA.
RP Hamza, I (reprint author), Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA.
EM hamza@umd.edu
RI Liu, Paul/A-7976-2012
OI Liu, Paul/0000-0002-6779-025X
FU National Institutes of Health [F32DK088439, R01DK80011, HL26922,
DK85035]; NIH/NHGRI Intramural Research Program
FX We thank Norma Andrews for the adenoviral plasmids, Vivek Malhotra for
HRP plasmid, Caiyong Chen for synthesis of HRP targeting plasmids, Naoko
Makise for help with macrophage setup, and Raman Sood for helpful
discussions. This work was supported by funding from the National
Institutes of Health F32DK088439 (C. W.), R01DK80011 (M. D. F.), HL26922
(D. M. W.), DK85035 (I. H.), and the NIH/NHGRI Intramural Research
Program (P. L.). Experimental design and execution were as follows:
macrophage and mammalian cell culture, C. W., T. K. S., X.Y., C. H., D.
M. W., and I. H.; yeast experiments, X.Y. and I. H.; mice and human
data, P.J.S., D. C., A. L., M. L. C., and M. D. F.; zebrafish
experiments, E. B., K. B., P. L., and I. H.; C. W. and I. H. wrote the
manuscript. All authors commented on the manuscript.
NR 57
TC 41
Z9 41
U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD FEB 5
PY 2013
VL 17
IS 2
BP 261
EP 270
DI 10.1016/j.cmet.2013.01.005
PG 10
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 242TL
UT WOS:000326265000012
PM 23395172
ER
PT J
AU Ghosh, MC
Zhang, DL
Jeong, SY
Kovtunovych, G
Ollivierre-Wilson, H
Noguchi, A
Tu, T
Senecal, T
Robinson, G
Crooks, DR
Tong, WH
Ramaswamy, K
Singh, A
Graham, BB
Tuder, RM
Yu, ZX
Eckhaus, M
Lee, J
Springer, DA
Rouault, TA
AF Ghosh, Manik C.
Zhang, De-Liang
Jeong, Suh Young
Kovtunovych, Gennadiy
Ollivierre-Wilson, Hayden
Noguchi, Audrey
Tu, Tiffany
Senecal, Thomas
Robinson, Gabrielle
Crooks, Daniel R.
Tong, Wing-Hang
Ramaswamy, Kavitha
Singh, Anamika
Graham, Brian B.
Tuder, Rubin M.
Yu, Zu-Xi
Eckhaus, Michael
Lee, Jaekwon
Springer, Danielle A.
Rouault, Tracey A.
TI Deletion of Iron Regulatory Protein 1 Causes Polycythemia and Pulmonary
Hypertension in Mice through Translational Derepression of HIF2 alpha
SO CELL METABOLISM
LA English
DT Article
ID HYPOXIA-INDUCIBLE FACTORS; ARTERIAL-HYPERTENSION; CHUVASH POLYCYTHEMIA;
TARGETED DELETION; MUTATION; HOMEOSTASIS; ERYTHROCYTOSIS; DEFICIENCY;
METABOLISM; PHYSIOLOGY
AB Iron regulatory proteins (Irps) 1 and 2 posttranscriptionally control the expression of transcripts that contain iron-responsive element (IRE) sequences, including ferritin, ferroportin, transferrin receptor, and hypoxia-inducible factor 2 alpha (HIF2 alpha). We report here that mice with targeted deletion of Irp1 developed pulmonary hypertension and polycythemia that was exacerbated by a low-iron diet. Hematocrits increased to 65% in iron-starved mice, and many polycythemic mice died of abdominal hemorrhages. Irp1 deletion enhanced HIF2a protein expression in kidneys of Irp1(-/-) mice, which led to increased erythropoietin (EPO) expression, polycythemia, and concomitant tissue iron deficiency. Increased HIF2a expression in pulmonary endothelial cells induced high expression of endothelin-1, likely contributing to the pulmonary hypertension of Irp1(-/-) mice. Our results reveal why anemia is an early physiological consequence of iron deficiency, highlight the physiological significance of Irp1 in regulating erythropoiesis and iron distribution, and provide important insights into the molecular pathogenesis of pulmonary hypertension.
C1 [Ghosh, Manik C.; Zhang, De-Liang; Jeong, Suh Young; Kovtunovych, Gennadiy; Ollivierre-Wilson, Hayden; Tu, Tiffany; Senecal, Thomas; Robinson, Gabrielle; Crooks, Daniel R.; Tong, Wing-Hang; Ramaswamy, Kavitha; Singh, Anamika; Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, Bethesda, MD 20892 USA.
[Noguchi, Audrey; Yu, Zu-Xi; Springer, Danielle A.] NHLBI, Murine Phenotyping Core, Bethesda, MD 20892 USA.
[Graham, Brian B.; Tuder, Rubin M.] Univ Colorado, Sch Med, Div Pulm Sci & Crit Care Med, Program Translat Lung Res,Dept Med, Denver, CO 80262 USA.
[Eckhaus, Michael] NIH, Vet Resources Program, Bethesda, MD 20892 USA.
[Lee, Jaekwon] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA.
RP Rouault, TA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, Bethesda, MD 20892 USA.
EM rouault@mail.nih.gov
RI Zhang, Deliang/F-7848-2013;
OI Zhang, Deliang/0000-0001-9478-5344; Jeong, Suh Young/0000-0002-6376-7001
FU NICHD; NHLBI; NIH [RC1HL100849]
FX This work was supported by the intramural programs of NICHD and NHLBI.
We thank Gregory Holmes-Hampton for helpful discussions, Michele Allen
for her help in mouse studies, Shawn Kozlov for blood gas measurements,
and Javier Seravalli for performing metal measurements. R.M.T.'s
research was supported by NIH (RC1HL100849). M. C. G. and D.-L.Z.
designed the study, generated data, performed analyses, and wrote the
paper. S.Y.J. and D. A. S. generated data, performed analyses, and wrote
the paper. G. K., A.N., D. R. C., B. B. G., Z.-X.Y., M. E., and J.L.
generated data and performed analyses. H.O.-W., T. T., T. S., G. R., K.
R., and A. S. generated data. W.-H. T. and R. M. T. provided substantial
intellectual contribution. T. A. R. designed the study, performed
analyses, and wrote the paper.
NR 37
TC 48
Z9 48
U1 0
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD FEB 5
PY 2013
VL 17
IS 2
BP 271
EP 281
DI 10.1016/j.cmet.2012.12.016
PG 11
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 242TL
UT WOS:000326265000013
PM 23395173
ER
PT J
AU Mandal, S
Mandal, A
Johansson, HE
Orjalo, AV
Park, MH
AF Mandal, Swati
Mandal, Ajeet
Johansson, Hans E.
Orjalo, Arturo V.
Park, Myung Hee
TI Depletion of cellular polyamines, spermidine and spermine, causes a
total arrest in translation and growth in mammalian cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE polyamine depletion; translational regulation; cell proliferation;
RNA-FISH
ID INITIATION-FACTOR 5A; YEAST SACCHAROMYCES-CEREVISIAE; HAMSTER OVARY
CELLS; ORNITHINE-DECARBOXYLASE; HYPUSINE MODIFICATION; TRANSGENIC MICE;
S-PHASE; N-1-ACETYLTRANSFERASE; OVEREXPRESSION; CANCER
AB The polyamines, putrescine, spermidine, and spermine, are essential polycations, intimately involved in the regulation of cellular proliferation. Although polyamines exert dynamic effects on the conformation of nucleic acids and macromolecular synthesis in vitro, their specific functions in vivo are poorly understood. We investigated the cellular function of polyamines by overexpression of a key catabolic enzyme, spermidine/spermine N-1-acetyltransferase 1 (SAT1) in mammalian cells. Transient cotransfection of HeLa cells with GFP and SAT1 vectors suppressed GFP protein expression without lowering its mRNA level, an indication that the block in GFP expression was not at transcription, but at translation. Fluorescence single-cell imaging also revealed specific inhibition of endogenous protein synthesis in the SAT1 overexpressing cells, without any inhibition of synthesis of DNA or RNA. Overexpression of SAT1 using a SAT1 adenovirus led to rapid depletion of cellular spermidine and spermine, total inhibition of protein synthesis, and growth arrest within 24 h. The SAT1 effect is most likely due to depletion of spermidine and spermine, because stable polyamine analogs that are not substrates for SAT1 restored GFP and endogenous protein synthesis. Loss of polysomes with increased 80S monosomes in the polyamine-depleted cells suggests a direct role for polyamines in translation initiation. Our data provide strong evidence for a primary function of polyamines, spermidine and spermine, in translation in mammalian cells.
C1 [Mandal, Swati; Mandal, Ajeet; Park, Myung Hee] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Johansson, Hans E.; Orjalo, Arturo V.] Biosearch Technol, Novato, CA 94949 USA.
RP Park, MH (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
EM mhpark@nih.gov
OI Johansson, Hans/0000-0001-9495-6107
FU Intramural Research Program of NIDCR, NIH
FX We thank Edith C. Wolff [National Institute of Dental and Craniofacial
Research (NIDCR), National Institutes of Health (NIH)] for helpful
suggestions on the manuscript; and Bill Swaim (NIDCR, NIH), Michael J.
Kruhlak (National Cancer Institute, NIH), and Duck-Yeon Lee (National
Heart, Blood, and Lung Institute, NIH) for providing their core
facilities and technical instructions. The research was supported in
part by the Intramural Research Program of NIDCR, NIH.
NR 39
TC 48
Z9 50
U1 2
U2 36
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 5
PY 2013
VL 110
IS 6
BP 2169
EP 2174
DI 10.1073/pnas.1219002110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 093RQ
UT WOS:000315209800048
PM 23345430
ER
PT J
AU Yan, D
Zhu, Y
Walsh, T
Xie, DH
Yuan, HJ
Sirmaci, A
Fujikawa, T
Wong, ACY
Loh, TL
Du, LL
Grati, M
Vlajkovic, SM
Blanton, S
Ryan, AF
Chen, ZY
Thorne, PR
Kachar, B
Tekin, M
Zhao, HB
Housley, GD
King, MC
Liu, XZ
AF Yan, Denise
Zhu, Yan
Walsh, Tom
Xie, Dinghua
Yuan, Huijun
Sirmaci, Asli
Fujikawa, Taro
Wong, Ann Chi Yan
Loh, Tze L.
Du, Lilin
Grati, M'hamed
Vlajkovic, Srdjan M.
Blanton, Susan
Ryan, Allen F.
Chen, Zheng-Yi
Thorne, Peter R.
Kachar, Bechara
Tekin, Mustafa
Zhao, Hong-Bo
Housley, Gary D.
King, Mary-Claire
Liu, Xue Z.
TI Mutation of the ATP-gated P2X(2) receptor leads to progressive hearing
loss and increased susceptibility to noise
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE channel; deafness; genomics; presbycusis
ID ION CHANNELS; AUDITORY NEUROTRANSMISSION; SOUND TRANSDUCTION; COCHLEAR
FUNCTION; RAT COCHLEA; SUBUNIT; MOUSE; LOCALIZATION; STEREOCILIA;
EXPRESSION
AB Age-related hearing loss and noise-induced hearing loss are major causes of human morbidity. Here we used genetics and functional studies to showthat a shared cause of these disordersmay be loss of function of the ATP-gated P2X(2) receptor (ligand-gated ion channel, purinergic receptor 2) that is expressed in sensory and supporting cells of the cochlea. Genomic analysis of dominantly inherited, progressive sensorineural hearing loss DFNA41 in a six-generation kindred revealed a rare heterozygous allele, P2RX2 c.178G > T (p.V60L), at chr12: 133,196,029, which cosegregated with fully penetrant hearing loss in the index family, and also appeared in a second family with the same phenotype. The mutation was absent from more than 7,000 controls. P2RX2 p.V60L abolishes two hallmark features of P2X(2) receptors: ATP-evoked inward current response and ATP-stimulated macropore permeability, measured as loss of ATP-activated FM1-43 fluorescence labeling. Coexpression of mutant and WT P2X(2) receptor subunits significantly reduced ATP-activated membrane permeability. P2RX2-null mice developed severe progressive hearing loss, and their early exposure to continuous moderate noise led to high-frequency hearing loss as young adults. Similarly, among family members heterozygous for P2RX2 p.V60L, noise exposure exacerbated high-frequency hearing loss in young adulthood. Our results suggest that P2X(2) function is required for life-long normal hearing and for protection from exposure to noise.
C1 [Yan, Denise; Du, Lilin; Grati, M'hamed; Liu, Xue Z.] Univ Miami, Sch Med, Dept Otolaryngol, Miami, FL 33136 USA.
[Zhu, Yan; Zhao, Hong-Bo] Univ Kentucky, Med Ctr, Dept Otolaryngol, Lexington, KY 40536 USA.
[Walsh, Tom; King, Mary-Claire] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Walsh, Tom; King, Mary-Claire] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Xie, Dinghua; Liu, Xue Z.] Cent S Univ, Dept Otolaryngol Head & Neck Surg, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China.
[Yuan, Huijun] Chinese Peoples Liberat Army Gen Hosp, Inst Otolaryngol, Beijing 100853, Peoples R China.
[Sirmaci, Asli; Blanton, Susan; Tekin, Mustafa; Liu, Xue Z.] Univ Miami, Sch Med, Dept Human Genet, Miami, FL 33136 USA.
[Fujikawa, Taro; Grati, M'hamed; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA.
[Wong, Ann Chi Yan; Loh, Tze L.; Housley, Gary D.] Univ New S Wales, Sch Med Sci, Translat Neurosci Facil, Sydney, NSW 2052, Australia.
[Wong, Ann Chi Yan; Loh, Tze L.; Housley, Gary D.] Univ New S Wales, Sch Med Sci, Dept Physiol, Sydney, NSW 2052, Australia.
[Vlajkovic, Srdjan M.; Thorne, Peter R.] Univ Auckland, Sch Med Sci, Dept Physiol, Auckland 1, New Zealand.
[Vlajkovic, Srdjan M.; Thorne, Peter R.] Univ Auckland, Sch Med Sci, Ctr Brain Res, Auckland 1, New Zealand.
[Vlajkovic, Srdjan M.; Thorne, Peter R.] Univ Auckland, Sch Populat Hlth, Sect Audiol, Auckland 1, New Zealand.
[Ryan, Allen F.] Univ Calif San Diego, Dept Otolaryngol, La Jolla, CA 92093 USA.
[Ryan, Allen F.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Chen, Zheng-Yi] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Eaton Peabody Lab,Dept Otol & Laryngol, Boston, MA 02114 USA.
RP King, MC (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA.
EM mcking@u.washington.edu; xliu@med.miami.edu
OI Walsh, Tom/0000-0002-8875-0310; Wong, Ann CY/0000-0001-7011-0369;
Housley, Gary/0000-0002-8413-588X; Vlajkovic, Srdjan/0000-0001-8548-6844
FU National Institutes of Health, National Institute on Deafness and Other
Communication Disorders [R01 DC012546, R01 DC005575, R01 DC005989, R01
HL105631, R01 DC009645, R01 DC000139, R01 DC005641]; Veterans'
Administration; Australia National Health and Medical Research Council
[630618]; New Zealand Marsden Fund; Health Research Council and Deafness
Research Foundation; People's Republic of China National Natural Science
Foundation [30528025]
FX We thank the families for their participation in the study. We thank
Menwei Cai, Pu Dai, Dongyi Han, Kaisun Li, Chunyu Liang, Zian Xiao, and
Shiming Yang for contributions to the fieldwork in China; Anne Thornton,
Ming Lee, Xiaomai Ouyang, and Suleyman Gulsuner for contributions to
genomics and bioinformatics; Kwang Pak, Eduardo Chavez, Jeremy Pinyon,
Rachel Morton-Jones, Sherif Tadros, and Yogeesan Sivakumaran for
contributions to the mouse experiments; Debra Cockayne for supporting
the establishment of the mouse model; Edward Crawford for designing and
engineering the environmental chambers; and Karen B. Avraham, Walter
Nance, Yanbin Zhang, and Jianxin Bao for helpful discussions. This work
was supported by the National Institutes of Health, National Institute
on Deafness and Other Communication Disorders [Grants R01 DC012546 (to
X.Z.L.), R01 DC005575 (to X.Z.L.), R01 DC005989 (to H.-B.Z.), R01
HL105631 (to Y.Z.), R01 DC009645 (to M. T.), R01 DC000139 (to A. F. R.),
and R01 DC005641 (to M.-C. K. and T. W.), and the intramural program (B.
K.)], the Veterans' Administration (A. F. R.), the Australia National
Health and Medical Research Council [Grant 630618 (to G. D. H. and A. F.
R.)], the New Zealand Marsden Fund (G. D. H.) and Health Research
Council and Deafness Research Foundation (P. R. T., G. D. H., and S. M.
V.), and the People's Republic of China National Natural Science
Foundation [Grant 30528025 (to X.Z.L.)].
NR 40
TC 31
Z9 36
U1 3
U2 19
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 5
PY 2013
VL 110
IS 6
BP 2228
EP 2233
DI 10.1073/pnas.1222285110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 093RQ
UT WOS:000315209800058
PM 23345450
ER
PT J
AU Baruch, K
Ron-Harel, N
Gal, H
Deczkowska, A
Shifrut, E
Ndifon, W
Mirlas-Neisberg, N
Cardon, M
Vaknin, I
Cahalon, L
Berkutzki, T
Mattson, MP
Gomez-Pinilla, F
Friedman, N
Schwartz, M
AF Baruch, Kuti
Ron-Harel, Noga
Gal, Hilah
Deczkowska, Aleksandra
Shifrut, Eric
Ndifon, Wilfred
Mirlas-Neisberg, Nataly
Cardon, Michal
Vaknin, Ilan
Cahalon, Liora
Berkutzki, Tamara
Mattson, Mark P.
Gomez-Pinilla, Fernando
Friedman, Nir
Schwartz, Michal
TI CNS-specific immunity at the choroid plexus shifts toward destructive
Th2 inflammation in brain aging
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE blood-cerebrospinal fluid barrier; brain senescence; neuroinflammation
ID CENTRAL-NERVOUS-SYSTEM; CD4(+) T-CELLS; CENTRAL MEMORY;
CEREBROSPINAL-FLUID; DENDRITIC CELLS; IFN-GAMMA; RAT-BRAIN;
NEUROGENESIS; IL-4; LUNG
AB The adaptive arm of the immune system has been suggested as an important factor in brain function. However, given the fact that interactions of neurons or glial cells with T lymphocytes rarely occur within the healthy CNS parenchyma, the underlying mechanism is still a mystery. Here we found that at the interface between the brain and blood circulation, the epithelial layers of the choroid plexus (CP) are constitutively populated with CD4(+) effector memory cells with a T-cell receptor repertoire specific to CNS antigens. With age, whereas CNS specificity in this compartment was largely maintained, the cytokine balance shifted in favor of the T helper type 2 (Th2) response; the Th2-derived cytokine IL-4 was elevated in the CP of old mice, relative to IFN-gamma, which decreased. We found this local cytokine shift to critically affect the CP epithelium, triggering it to produce the chemokine CCL11 shown to be associated with cognitive dysfunction. Partial restoration of cognitive ability in aged mice, by lymphopenia-induced homeostasis-driven proliferation of memory T cells, was correlated with restoration of the IL-4:IFN-gamma ratio at the CP and modulated the expression of plasticity-related genes at the hippocampus. Our data indicate that the cytokine milieu at the CP epithelium is affected by peripheral immunosenescence, with detrimental consequences to the aged brain. Amenable to immunomodulation, this interface is a unique target for arresting age-related cognitive decline.
C1 [Baruch, Kuti; Deczkowska, Aleksandra; Mirlas-Neisberg, Nataly; Cardon, Michal; Vaknin, Ilan; Cahalon, Liora; Berkutzki, Tamara; Schwartz, Michal] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel.
[Gal, Hilah; Shifrut, Eric; Ndifon, Wilfred; Friedman, Nir] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.
[Ron-Harel, Noga] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Gomez-Pinilla, Fernando] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90095 USA.
[Gomez-Pinilla, Fernando] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA.
RP Schwartz, M (reprint author), Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel.
EM michal.schwartz@weizmann.ac.il
RI Baruch, Kuti/I-3535-2016;
OI Baruch, Kuti/0000-0002-1466-8795; Shifrut, Eric/0000-0001-6827-0128
FU European Research Council; National Institute on Aging
FX We thank Dr. Gilad Kunis for technical assistance, Dr. Shelley
Schwarzbaum for editing the manuscript, Dr. Hillary Voet for statistical
consultation, and Margalit Azoulay for animal handling. This research
was supported by a European Research Council Grant Award, a Seventh
Framework Programme HEALTH-2011 Grant (to M. S.), and by the Intramural
Research Program of the National Institute on Aging (to M. P. M.). N.F.
is the incumbent Pauline Recanati Career Development Chair of
Immunology. M. S. holds The Maurice and Ilse Katz Professorial Chair in
Neuroimmunology.
NR 47
TC 71
Z9 71
U1 1
U2 11
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 5
PY 2013
VL 110
IS 6
BP 2264
EP 2269
DI 10.1073/pnas.1211270110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 093RQ
UT WOS:000315209800064
PM 23335631
ER
PT J
AU Khormaee, S
Choi, Y
Shen, MJ
Xu, BY
Wu, HT
Griffiths, GL
Chen, RJ
Slater, NKH
Park, JK
AF Khormaee, Sariah
Choi, Yong
Shen, Michael J.
Xu, Biying
Wu, Haitao
Griffiths, Gary L.
Chen, Rongjun
Slater, Nigel K. H.
Park, John K.
TI Endosomolytic Anionic Polymer for the Cytoplasmic Delivery of siRNAs in
Localized In Vivo Applications
SO ADVANCED FUNCTIONAL MATERIALS
LA English
DT Article
DE siRNA delivery; anionic polymers; endosomes; tumor treatment;
glioblastoma; stathmin
ID RESPONSIVE PSEUDO-PEPTIDES; MAMMALIAN-CELLS; PH; RNAI; INTERFERENCE;
NITROSOUREAS; DISRUPTION; CONJUGATE; STATHMIN
AB The use of small interfering RNAs (siRNAs) to down-regulate the expression of disease-associated proteins carries significant promise for the treatment of a variety of clinical disorders. One of the main barriers to the widespread clinical use of siRNAs, however, is their entrapment and degradation within the endolysosomal pathway of target cells. Here, the trafficking and function of PP75, a nontoxic, biodegradable, lipid membrane disruptive anionic polymer composed of phenylalanine derivatized poly(L-lysine isophthalamide) is reported. PP75 is readily endocytosed by cells, safely permeabilizes endolysosomes in a pH dependent manner and facilitates the transfer of co-endocytosed materials directly into the cytoplasm. The covalent attachment of siRNAs to PP75 using disulfide linkages generates conjugates that effectively traffic siRNAs to the cytoplasm of target cells both in vitro and in vivo. In a subcutaneous malignant glioma tumor model, a locally delivered PP75-stathmin siRNA conjugate decreases stathmin expression in tumor cells and, in combination with the nitrosourea chemotherapy carmustine, is highly effective at inhibiting tumor growth. PP75 may be clinically useful for the local delivery of siRNAs, in particular for the treatment of solid tumors.
C1 [Khormaee, Sariah; Choi, Yong; Shen, Michael J.; Park, John K.] NINDS, Surg & Mol Neurooncol Unit, NIH, Bethesda, MD 20892 USA.
[Khormaee, Sariah; Slater, Nigel K. H.] Univ Cambridge, Dept Chem Engn & Biotechnol, Cambridge CB2 3RA, England.
[Xu, Biying; Wu, Haitao; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA.
[Chen, Rongjun] Univ Leeds, Ctr Mol Nanosci, Sch Chem, Leeds LS2 9JT, W Yorkshire, England.
RP Khormaee, S (reprint author), NINDS, Surg & Mol Neurooncol Unit, NIH, Bethesda, MD 20892 USA.
EM parkjk@ninds.nih.gov
OI Chen, Rongjun/0000-0002-8133-5472
FU NINDS intramural research program of the NIH; NHLBI intramural research
program of the NIH; NIH/Marshall fund; NIH Roadmap for Medical Research
Initiative of the NIH
FX This work was supported by the NINDS and NHLBI intramural research
programs of the NIH and the NIH/Marshall fund. The Imaging Probe
Development Center is supported by the NIH Roadmap for Medical Research
Initiative of the NIH. We thank Dragan Maric for assistance with FACS
analyses and Carolyn Smith for assistance with microscopy. There are no
conflicts of interest to report.
NR 25
TC 8
Z9 8
U1 1
U2 51
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1616-301X
J9 ADV FUNCT MATER
JI Adv. Funct. Mater.
PD FEB 5
PY 2013
VL 23
IS 5
BP 565
EP 574
DI 10.1002/adfm.201201945
PG 10
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA 083MO
UT WOS:000314468600005
ER
PT J
AU Himes, SK
Scheidweiler, KB
Tassiopoulos, K
Kacanek, D
Hazra, R
Rich, K
Huestis, MA
AF Himes, Sarah K.
Scheidweiler, Karl B.
Tassiopoulos, Katherine
Kacanek, Deborah
Hazra, Rohan
Rich, Kenneth
Huestis, Marilyn A.
CA Pediat HIV AIDS Cohort Study
TI Development and Validation of the First Liquid Chromatography-Tandem
Mass Spectrometry Assay for Simultaneous Quantification of Multiple
Antiretrovirals in Meconium
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID PERSISTENT MITOCHONDRIAL DYSFUNCTION; REVERSE-TRANSCRIPTASE INHIBITOR;
UNINFECTED CHILDREN; IN-UTERO; MATERNAL INTERVIEW; AMNIOTIC-FLUID;
LC-MS; EXPOSURE; PREGNANCY; PLASMA
AB A novel method for the simultaneous quantification of 16 antiretroviral (ARV) drugs and 4 metabolites in meconium was developed and validated. Quantification of 6 nucleoside/nucleotide reverse transcriptase inhibitors, 2 non-nucleoside reverse transcriptase inhibitors, 7 protease inhibitors, and 1 integrase inhibitor was achieved in 0.25 g of meconium. Specimen preparation included methanol homogenization and solid-phase extraction. Separate positive and negative polarity multiple reaction monitoring mode injections were required to achieve sufficient sensitivity. Linearity ranged from 10 to 75 ng/g up to 2500 ng/g for most analytes and 100-500 ng/g up to 25 000 ng/g for some; all correlation coefficients were >= 99. Extraction efficiencies from meconium were 32.8-119.5% with analytical recovery of 80.3-108.3% and total imprecision of 2.2-11.0% for all quantitative analytes. Two analytes with analytical recovery (70.0-138.5%) falling outside the 80-120% criteria range were considered semiquantitative. Matrix effects were -98.3-47.0% and -98.0-67.2% for analytes and internal standards, respectively. Analytes were stable (>75%) at room temperature for 24 h, 4 degrees C for 3 days, -20 degrees C for 3 freeze-thaw cycles over 3 days, and on the autosampler. Method applicability was demonstrated by analyzing meconium from HIV-uninfected infants born to HIV-positive mothers on ARV therapy. This method can be used as a tool to investigate the potential effects of in utero ARV exposure on childhood health and neurodevelopmental outcomes.
C1 [Himes, Sarah K.; Scheidweiler, Karl B.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, Intramural Res Program, Baltimore, MD 21224 USA.
[Tassiopoulos, Katherine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Kacanek, Deborah] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Hazra, Rohan] NICHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA.
[Rich, Kenneth] Univ Illinois, Dept Pediat, Chicago, IL 60612 USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute on Drug Abuse; National Institute of
Allergy and Infectious Diseases; Office of AIDS Research; National
Institute of Mental Health; National Institute of Neurological Disorders
and Stroke; National Institute on Deafness and Other Communication
Disorders; National Heart Lung and Blood Institute; National Institute
of Dental and Craniofacial Research; National Institute on Alcohol Abuse
and Alcoholism through Harvard University School of Public Health
[HD052102, 3 U01 HD052102-05S1, 3 U01 HD052102-06S3]; Tulane University
School of Medicine [HD052104, 3U01HD052104-06S1]
FX We thank the children and families for their participation in PHACS and
the individuals and institutions involved in the conduct of PHACS. The
study was supported by the Eunice Kennedy Shriver National Institute of
Child Health and Human Development with cofunding from the National
Institute on Drug Abuse, the National Institute of Allergy and
Infectious Diseases, the Office of AIDS Research, the National Institute
of Mental Health, the National Institute of Neurological Disorders and
Stroke, the National Institute on Deafness and Other Communication
Disorders, the National Heart Lung and Blood Institute, the National
Institute of Dental and Craniofacial Research, and the National
Institute on Alcohol Abuse and Alcoholism, through cooperative
agreements with the Harvard University School of Public Health
(HD052102, 3 U01 HD052102-05S1, 3 U01 HD052102-06S3) (Principal
Investigator: George Seage; Project Director: Julie Alperen) and the
Tulane University School of Medicine (HD052104, 3U01HD052104-06S1)
(Principal Investigator: Russell Van Dyke; Co-Principal Investigator:
Kenneth Rich; Project Director: Patrick Davis). Data management services
were provided by Frontier Science and Technology Research Foundation
(PI: Suzanne Siminski), and regulatory services and logistical support
were provided by Westat, Inc (PI: Julie Davidson).
NR 36
TC 7
Z9 7
U1 1
U2 20
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD FEB 5
PY 2013
VL 85
IS 3
BP 1896
EP 1904
DI 10.1021/ac303188j
PG 9
WC Chemistry, Analytical
SC Chemistry
GA 086IA
UT WOS:000314676100092
PM 23256731
ER
PT J
AU Jensen, RA
Sim, XL
Li, XH
Cotch, MF
Ikram, MK
Holliday, EG
Eiriksdottir, G
Harris, TB
Jonasson, F
Klein, BEK
Launer, LJ
Smith, AV
Boerwinkle, E
Cheung, N
Hewitt, AW
Liew, G
Mitchell, P
Wang, JJ
Attia, J
Scott, R
Glazer, NL
Lumley, T
McKnight, B
Psaty, BM
Taylor, K
Hofman, A
de Jong, PTVM
Rivadeneira, F
Uitterlinden, AG
Tay, WT
Teo, YY
Seielstad, M
Liu, JJ
Cheng, CY
Saw, SM
Aung, T
Ganesh, SK
O'Donnell, CJ
Nalls, MA
Wiggins, KL
Kuo, JZ
van Duijn, CM
Gudnason, V
Klein, R
Siscovick, DS
Rotter, JI
Tai, ES
Vingerling, J
Wong, TY
AF Jensen, Richard A.
Sim, Xueling
Li, Xiaohui
Cotch, Mary Frances
Ikram, M. Kamran
Holliday, Elizabeth G.
Eiriksdottir, Gudny
Harris, Tamara B.
Jonasson, Fridbert
Klein, Barbara E. K.
Launer, Lenore J.
Smith, Albert Vernon
Boerwinkle, Eric
Cheung, Ning
Hewitt, Alex W.
Liew, Gerald
Mitchell, Paul
Wang, Jie Jin
Attia, John
Scott, Rodney
Glazer, Nicole L.
Lumley, Thomas
McKnight, Barbara
Psaty, Bruce M.
Taylor, Kent
Hofman, Albert
de Jong, Paulus T. V. M.
Rivadeneira, Fernando
Uitterlinden, Andre G.
Tay, Wan-Ting
Teo, Yik Ying
Seielstad, Mark
Liu, Jianjun
Cheng, Ching-Yu
Saw, Seang-Mei
Aung, Tin
Ganesh, Santhi K.
O'Donnell, Christopher J.
Nalls, Mike A.
Wiggins, Kerri L.
Kuo, Jane Z.
van Duijn, Cornelia M.
Gudnason, Vilmundur
Klein, Ronald
Siscovick, David S.
Rotter, Jerome I.
Tai, E. Shong
Vingerling, Johannes
Wong, Tien Y.
CA Blue Mt Eye Study GWAS Team
CKDGen Consortium
TI Genome-Wide Association Study of Retinopathy in Individuals without
Diabetes
SO PLOS ONE
LA English
DT Article
ID RETINAL MICROVASCULAR ABNORMALITIES; ANTIHYPERTENSIVE DRUG THERAPIES;
ATHEROSCLEROSIS RISK; BLOOD-PRESSURE; CARDIOVASCULAR HEALTH;
HYPERTENSION; COMMUNITIES; MORTALITY; DESIGN; STROKE
AB Background: Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes.
Methods: A working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs) previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy.
Results: No SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9) on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, -1.3 +/- 0.23 (beta +/- standard error), p=6.6x10(-9). Evidence suggests this was a false positive finding. The minor allele frequency was low (similar to 2%), the quality of the imputation was moderate (r(2) similar to 0.7), and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension.
Conclusions: This GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases.
C1 [Jensen, Richard A.; Lumley, Thomas; McKnight, Barbara; Psaty, Bruce M.; Wiggins, Kerri L.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Jensen, Richard A.; Psaty, Bruce M.; Wiggins, Kerri L.; Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA USA.
[Sim, Xueling; Teo, Yik Ying] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore.
[Li, Xiaohui; Taylor, Kent; Kuo, Jane Z.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Ikram, M. Kamran; Tay, Wan-Ting; Cheng, Ching-Yu; Saw, Seang-Mei; Aung, Tin; Wong, Tien Y.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
[Ikram, M. Kamran; Vingerling, Johannes] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands.
[Holliday, Elizabeth G.; Attia, John] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia.
[Eiriksdottir, Gudny; Smith, Albert Vernon; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Jonasson, Fridbert; Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Dept Med, Reykjavik, Iceland.
[Jonasson, Fridbert] Landspitalinn Univ Hosp, Dept Ophthalmol, Reykjavik, Iceland.
[Klein, Barbara E. K.; Klein, Ronald] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA.
[Cheung, Ning; Hewitt, Alex W.; Liew, Gerald; Wang, Jie Jin; Wong, Tien Y.] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia.
[Liew, Gerald; Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Ctr Vis Res, Dept Ophthalmol, Sydney, NSW 2006, Australia.
[Liew, Gerald; Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Westmead Millennium Inst, Sydney, NSW 2006, Australia.
[Attia, John] John Hunter Hosp, Dept Med, Newcastle, NSW, Australia.
[Attia, John] Hunter Med Res Inst, Newcastle, NSW, Australia.
[Scott, Rodney] Univ Newcastle, Sch Biomed Sci, Newcastle, NSW 2300, Australia.
[Glazer, Nicole L.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA.
[Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand.
[McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Psaty, Bruce M.; Siscovick, David S.] 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.
[Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Vingerling, Johannes] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[de Jong, Paulus T. V. M.] Netherlands Inst Neurosci, Amsterdam, Netherlands.
[de Jong, Paulus T. V. M.] Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands.
[Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Uitterlinden, Andre G.] Erasmus MC, Dept Clin Chem, Rotterdam, Netherlands.
[Teo, Yik Ying; Cheng, Ching-Yu; Saw, Seang-Mei; Tai, E. Shong] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Singapore 117548, Singapore.
[Teo, Yik Ying] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore.
[Teo, Yik Ying] Natl Univ Singapore, NUS Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore.
[Teo, Yik Ying; Liu, Jianjun] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore.
[Seielstad, Mark] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Cheng, Ching-Yu; Saw, Seang-Mei; Aung, Tin; Wong, Tien Y.] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore.
[Ganesh, Santhi K.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[O'Donnell, Christopher J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Nalls, Mike A.] NIA, Neurogenet Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Tai, E. Shong] Natl Univ Singapore, Singapore 117548, Singapore.
[Tai, E. Shong] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore.
RP Jensen, RA (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
EM richaj@uw.edu
RI Cheng, Ching-Yu/K-7017-2013; Attia, John/F-5376-2013; Wang, Jie
Jin/P-1499-2014; Mitchell, Paul/P-1498-2014; Hewitt, Alex/D-1936-2013;
Cheung, Ning Danny/F-2043-2013; Gudnason, Vilmundur/K-6885-2015;
Rivadeneira, Fernando/O-5385-2015; Smith, Albert/K-5150-2015;
OI Klein, Ronald/0000-0002-4428-6237; Ikram, Mohammad
Kamran/0000-0003-0173-9571; Tai, E Shyong/0000-0003-2929-8966; Cheng,
Ching-Yu/0000-0003-0655-885X; Attia, John/0000-0001-9800-1308; Wang, Jie
Jin/0000-0001-9491-4898; Hewitt, Alex/0000-0002-5123-5999; Gudnason,
Vilmundur/0000-0001-5696-0084; Rivadeneira,
Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845; Cotch,
Mary Frances/0000-0002-2046-4350; Seielstad, Mark/0000-0001-5783-1401
FU National Institutes of Health (NIH) [N01-AG-12100]; National Institute
on Aging Intramural Research Program at the NIH [ZIAAG007380,
ZIAEY000401]; National Eye Institute Intramural Research Program at the
NIH [ZIAAG007380, ZIAEY000401]; Hjartavernd (the Icelandic Heart
Association); Althingi (the Icelandic Parliament); National Heart, Lung,
and Blood Institute [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641,
R01HL59367, R01HL086694]; National Human Genome Research Institute
[U01HG004402]; National Institutes of Health [HHSN268200625226C];
National Institutes of Health and NIH Roadmap for Medical Research
[UL1RR025005]; Australian National Health & Medical Research Council
(NHMRC) [974159, 991407, 211069, 457349]; NHMRC [512423, 475604, 529912,
590204]; Wellcome Trust, UK as part of Wellcome Trust Case Control
Consortium; genotyping costs of the entire BMES population
[085475/B/08/Z, 085475/08/Z]; National Heart, Lung, and Blood Institute
(NHLBI) [N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01
HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133]; NHLBI [HL080295,
HL075366, HL087652, HL105756, N02-HL-6-4278]; National Institute on
Aging [AG-023629, AG-15928, AG-20098, AG-027058]; Clinical Translational
Science Institute [UL1RR033176]; National Institute of Diabetes and
Digestive and Kidney Diseases [DK063491]; Cedars-Sinai Board of
Governors' Chair in Medical Genetics (JIR); Netherlands Organization of
Scientific Research NWO [175.010.2005.011]; Erasmus Medical Center,
Rotterdam; Erasmus University, Rotterdam; Netherlands Organization for
Scientific Research; Netherlands Organization for Health Research and
Development; Research Institute for Diseases in the Elderly; Ministry of
Education, Culture and Science; Ministry for Health, Welfare and Sports;
European Commission (DG XII) the Netherlands; Municipality of Rotterdam;
Lijf en Leven, Krimpen a/d Lek the Netherlands; MD Fonds, Utrecht the
Netherlands; Oogfonds Nederland, Utrecht the Netherlands; Stichting
Nederlands Oogheelkundig Onderzoek, Nijmegen/Rotterdam the Netherlands;
Swart van Essen, Rotterdam the Netherlands; Netherlands Organisation for
Scientific Research the Netherlands; Bevordering van Volkskracht,
Rotterdam the Netherlands; Blindenhulp, The Hague the Netherlands;
Rotterdamse Vereniging Blindenbelangen, Rotterdam the Netherlands; OOG,
The Hague the Netherlands; Algemene Nederlandse Vereniging ter
Voorkoming van Blindheid, Doorn the Netherlands; Blinden-Penning,
Amsterdam the Netherlands; Blindenhulp, 's Gravenzande the Netherlands;
Henkes Stichting, Rotterdam the Netherlands; Topcon Europe BV, Capelle
aan de IJssel the Netherlands; Medical Workshop BV, Groningen the
Netherlands; [N01 HC-95159]; [N01-HC-95169]; [RR-024156]
FX The authors declare that they have no relevant financial interests. Age,
Gene/Environment Susceptibility-Reykjavik Study has been funded by
National Institutes of Health (NIH) contract N01-AG-12100, the National
Institute on Aging and National Eye Institute Intramural Research
Programs at the NIH (ZIAAG007380 and ZIAEY000401), Hjartavernd (the
Icelandic Heart Association), and the Althingi (the Icelandic
Parliament). The Atherosclerosis Risk in Communities Study is carried
out as a collaborative study supported by National Heart, Lung, and
Blood Institute contracts HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641,
R01HL59367 and R01HL086694; National Human Genome Research Institute
contract U01HG004402; and National Institutes of Health contract
HHSN268200625226C. Infrastructure was partly supported by Grant Number
UL1RR025005, a component of the National Institutes of Health and NIH
Roadmap for Medical Research. The Blue Mountains Eye Study (BMES) was
supported by the Australian National Health & Medical Research Council
(NHMRC) grants (IDs 974159, 991407, 211069 and 457349). The genome-wide
association study was supported by the following grants: NHMRC project
grants IDs 512423, 475604, 529912 and 590204, and funding by the
Wellcome Trust, UK as part of Wellcome Trust Case Control Consortium 2
(A Viswanathan, P McGuffin, P Mitchell, F Topouzis, P Foster), which
supported the genotyping costs of the entire BMES population (Grant
numbers 085475/B/08/Z and 085475/08/Z). The Cardiovascular Health Study
research was supported by National Heart, Lung, and Blood Institute
(NHLBI) contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086;
N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and
NHLBI grants HL080295, HL075366, HL087652, HL105756 with additional
contribution from the National Institute of Neurological Disorders and
Stroke. Additional support was provided through AG-023629, AG-15928,
AG-20098, and AG-027058 from the National Institute on Aging. See also
http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping was
supported in part by the Clinical Translational Science Institute grant
UL1RR033176 to the Cedars-Sinai General Clinical Research Center
Genotyping core and National Institute of Diabetes and Digestive and
Kidney Diseases grant DK063491 to the Southern California Diabetes
Endocrinology Research Center. Additional funding was provided by the
Cedars-Sinai Board of Governors' Chair in Medical Genetics (JIR). The
Multi-Ethnic Study of Atherosclerosis (MESA) and MESA SNP Health
Association Resource (SHARe) are conducted and supported by the National
Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA
investigators. Support is provided by grants and contracts N01 HC-95159
through N01-HC-95169 and RR-024156. Funding for SHARe genotyping was
provided by NHLBI Contract N02-HL-6-4278. The authors thank the other
investigators, the staff, and the participants of the MESA study for
their valuable contributions. A full list of participating MESA
investigators and institutions can be found at
http://www.mesa-nhlbi.org. The GWA database of the Rotterdam Study was
funded through the Netherlands Organization of Scientific Research NWO
(nr. 175.010.2005.011).; The Rotterdam Study is supported by the Erasmus
Medical Center and Erasmus University, Rotterdam; the Netherlands
Organization for Scientific Research, the Netherlands Organization for
Health Research and Development, the Research Institute for Diseases in
the Elderly, the Ministry of Education, Culture and Science, the
Ministry for Health, Welfare and Sports, the European Commission (DG
XII), and the Municipality of Rotterdam. The ophthalmologic part of the
Rotterdam Study was supported by Lijf en Leven, Krimpen a/d Lek; MD
Fonds, Utrecht. Oogfonds Nederland, Utrecht; Stichting Nederlands
Oogheelkundig Onderzoek, Nijmegen/Rotterdam; Swart van Essen, Rotterdam;
Netherlands Organisation for Scientific Research; Bevordering van
Volkskracht, Rotterdam; Blindenhulp, The Hague; Rotterdamse Vereniging
Blindenbelangen, Rotterdam; OOG, The Hague; Algemene Nederlandse
Vereniging ter Voorkoming van Blindheid, Doorn; Blinden-Penning,
Amsterdam; Blindenhulp, 's Gravenzande; Henkes Stichting, Rotterdam;
Topcon Europe BV, Capelle aan de IJssel; Medical Workshop BV, Groningen;
all in the Netherlands; Heidelberg Engineering, Dossenheim, Germany. The
Singapore Indian Eye Study was funded by grants from the Biomedical
Research Council of Singapore (BMRC 09/1/35/19/616 and BMRC
08/1/35/19/550) and the National Medical Research Council of Singapore
(NMRC/STaR/0003/2008). The Singapore BioBank and the Genome Institute of
Singapore, Agency for Science, Technology and Research, Singapore
provided services for tissue archival and genotyping. 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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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 FEB 5
PY 2013
VL 8
IS 2
AR e54232
DI 10.1371/journal.pone.0054232
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 086NV
UT WOS:000314692800009
PM 23393555
ER
PT J
AU Sun, YL
Chen, JJ
Kumar, P
Chen, K
Sodani, K
Patel, A
Chen, YL
Chen, SD
Jiang, WQ
Chen, ZS
AF Sun, Yue-Li
Chen, Jun-Jiang
Kumar, Priyank
Chen, Kang
Sodani, Kamlesh
Patel, Atish
Chen, Yang-Lu
Chen, Si-Dong
Jiang, Wen-Qi
Chen, Zhe-Sheng
TI Reversal of MRP7 (ABCC10)-Mediated Multidrug Resistance by Tariquidar
SO PLOS ONE
LA English
DT Article
ID P-GLYCOPROTEIN INHIBITOR; ABC TRANSPORTERS; PROTEIN BCRP/ABCG2;
SIGNALING PATHWAY; PHASE-I; CANCER; XR9576; PACLITAXEL; CELLS;
CHEMOTHERAPY
AB Multidrug resistance protein 7 (MRP7, ABCC10) is a recently discovered member of the ATP-binding cassette (ABC) family which are capable of conferring resistance to a variety of anticancer drugs, including taxanes and nucleoside analogs, in vivo. MRP7 is highly expressed in non-small cell lung cancer cells, and Mrp7-KO mice are highly sensitive to paclitaxel, making MRP7 an attractive chemotherapeutic target of non-small cell lung cancer. However, only a few inhibitors of MRP7 are currently identified, with none of them having progressed to clinical trials. We used MRP7-expressing cells to investigate whether tariquidar, a third generation inhibitor of P-glycoprotein, could inhibit MRP7-mediated multidrug resistance (MDR). We found that tariquidar, at 0.1 and 0.3 mu M, significantly potentiated the sensitivity of MRP7-transfected HEK293 cells to MRP7 substrates and increased the intracellular accumulation of paclitaxel. We further demonstrated that tariquidar directly impaired paclitaxel efflux and could downregulate MRP7 protein expression in a concentration-and time-dependent manner after prolonged treatment. Our findings suggest that tariquidar, at pharmacologically achievable concentrations, reverses MRP7-mediated MDR through inhibition of MRP7 protein expression and function, and thus represents a promising therapeutic agent in the clinical treatment of chemoresistant cancer patients.
C1 [Sun, Yue-Li; Jiang, Wen-Qi] State Key Lab Oncol S China, Guangzhou, Guangdong, Peoples R China.
[Sun, Yue-Li; Jiang, Wen-Qi] Sun Yat Sen Univ, Ctr Canc, Dept Med Oncol, Guangzhou 510275, Guangdong, Peoples R China.
[Sun, Yue-Li; Chen, Jun-Jiang; Kumar, Priyank; Sodani, Kamlesh; Patel, Atish; Chen, Yang-Lu; Chen, Zhe-Sheng] St Johns Univ, Dept Pharmaceut Sci, Coll Pharm & Hlth Sci, Queens, NY USA.
[Chen, Jun-Jiang; Chen, Si-Dong] Guangdong Pharmaceut Univ, Sch Publ Hlth, Guangdong Key Lab Mol Epidemiol, Guangzhou, Guangdong, Peoples R China.
[Chen, Kang] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Chen, Kang] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Bethesda, MD USA.
[Chen, Yang-Lu] Montgomery High Sch, Skillman, NJ USA.
RP Jiang, WQ (reprint author), State Key Lab Oncol S China, Guangzhou, Guangdong, Peoples R China.
EM wqjiang@yahoo.com; chenz@stjohns.edu
RI Patel, Atish/J-4699-2014
OI Kumar, Priyank/0000-0002-4772-2073; Patel, Atish/0000-0002-5549-9166
FU National Institutes of Health [1R15CA143701]; St. John's University
Research Seed Grant [579-1110-7002]
FX This work was supported by funds from National Institutes of Health
(number 1R15CA143701) and St. John's University Research Seed Grant
(number 579-1110-7002) to Z.S. Chen. 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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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 FEB 5
PY 2013
VL 8
IS 2
AR e55576
DI 10.1371/journal.pone.0055576
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 086NV
UT WOS:000314692800048
PM 23393594
ER
PT J
AU Stevens, AJ
Guan, LR
Bebenek, K
Kunkel, TA
Greenberg, MM
AF Stevens, Adam J.
Guan, Lirui
Bebenek, Katarzyna
Kunkel, Thomas A.
Greenberg, Marc M.
TI DNA Polymerase lambda Inactivation by Oxidized Abasic Sites
SO BIOCHEMISTRY
LA English
DT Article
ID BASE-EXCISION-REPAIR; HISTONE-CATALYZED CLEAVAGE; DOUBLE-STRAND
CLEAVAGE; CROSS-LINK FORMATION; ESCHERICHIA-COLI; LYASE ACTIVITY; FE
BLEOMYCIN; A-RULE; LESION; MECHANISM
AB Base excision repair (BER) plays a vital role in maintaining genomic integrity in mammalian cells. DNA polymerase lambda (Pol lambda) is believed to play a backup role to DNA polymerase beta (Pol beta) in base excision repair. Two oxidized abasic lesions that are produced by a variety of DNA-damaging agents, including several antitumor antibiotics, the C4'-oxidized abasic site following Ape1 incision (pC4-AP), and 5'-(2-phosphoryl-1,4-dioxobutane) (DOB), irreversibly inactivate Pol beta and Pol lambda. The interactions of DOB and pC4-AP with Pol lambda are examined in detail using DNA substrates containing these lesions at defined sites. Single-turnover kinetic experiments show that Pol lambda excises DOB almost 13 times more slowly than a 5'-phosphorylated 2-deoxyribose (dRP). pC4-AP is excised approximately twice as fast as DOB. The absolute rate constants are considerably slower than those reported for Pol beta for the respective reactions, suggesting that Pol lambda may be an inefficient backup in BER DOB inactivates Pol lambda approximately 3-fold less efficiently than it does Pol beta, and the difference can be attributed to a higher K-1 (33 +/- 7 nM). Inactivation of Pol lambda's lyase activity by DOB also prevents the enzyme from conducting polymerization following preincubation of the protein and DNA. Mass spectral analysis of GluC-digested Pol lambda inactivated by DOB shows that Lys324 is modified. There is inferential support for the idea that Lys312 may also be modified. Both residues are within the Pol lambda lyase active site. When acting on pC4-AP, Pol lambda achieves approximately four turnovers on average before being inactivated. Lyase inactivation by pC4-AP is also accompanied by loss of polymerase activity, and mass spectrometry indicates that Lys312 and Lys324 are modified by the lesion. The ability of DOB and pC4-AP to inactivate Pol lambda provides additional evidence that these lesions are significant sources of the cytotoxicity of DNA-damaging agents that produce them.
C1 [Stevens, Adam J.; Guan, Lirui; Greenberg, Marc M.] Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA.
[Bebenek, Katarzyna; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
RP Greenberg, MM (reprint author), Johns Hopkins Univ, Dept Chem, 3400 N Charles St, Baltimore, MD 21218 USA.
EM mgreenberg@jhu.edu
RI Guan, Lirui/E-5611-2013
FU National Institute of General Medical Sciences [GM- 063028]; Division of
Intramural Research of the National Institutes of Health, National
Institute of Environmental Health Sciences [Z01 ES065070]
FX We are grateful for support of this research by National Institute of
General Medical Sciences Grant GM- 063028 to M.M.G. This work was
supported in part 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.
NR 55
TC 8
Z9 8
U1 0
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD FEB 5
PY 2013
VL 52
IS 5
BP 975
EP 983
DI 10.1021/bi301592x
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 086HX
UT WOS:000314675800021
PM 23330920
ER
PT J
AU Ramsden, CE
Zamora, D
Leelarthaepin, B
Majchrzak-Hong, SF
Faurot, KR
Suchindran, CM
Ringel, A
Davis, JM
Hibbeln, JR
AF Ramsden, Christopher E.
Zamora, Daisy
Leelarthaepin, Boonseng
Majchrzak-Hong, Sharon F.
Faurot, Keturah R.
Suchindran, Chirayath M.
Ringel, Amit
Davis, John M.
Hibbeln, Joseph R.
TI Use of dietary linoleic acid for secondary prevention of coronary heart
disease and death: evaluation of recovered data from the Sydney Diet
Heart Study and updated meta-analysis
SO BMJ-BRITISH MEDICAL JOURNAL
LA English
DT Article
ID POLYUNSATURATED FATTY-ACIDS; HUMAN ATHEROSCLEROTIC LESIONS; RANDOMIZED
CONTROLLED-TRIALS; LOW-DENSITY-LIPOPROTEIN; SMOOTH-MUSCLE-CELLS;
CARDIOVASCULAR-DISEASE; SERUM-CHOLESTEROL; OXIDIZED LDL;
EICOSAPENTAENOIC ACID; MYOCARDIAL-INFARCTION
AB Objective To evaluate the effectiveness of replacing dietary saturated fat with omega 6 linoleic acid, for the secondary prevention of coronary heart disease and death.
Design Evaluation of recovered data from the Sydney Diet Heart Study, a single blinded, parallel group, randomized controlled trial conducted in 1966-73; and an updated meta-analysis including these previously missing data.
Setting Ambulatory, coronary care clinic in Sydney, Australia.
Participants 458 men aged 30-59 years with a recent coronary event.
Interventions Replacement of dietary saturated fats (from animal fats, common margarines, and shortenings) with omega 6 linoleic acid (from safflower oil and safflower oil polyunsaturated margarine). Controls received no specific dietary instruction or study foods. All non-dietary aspects were designed to be equivalent in both groups.
Outcome measures All cause mortality (primary outcome), cardiovascular mortality, and mortality from coronary heart disease (secondary outcomes). We used an intention to treat, survival analysis approach to compare mortality outcomes by group. Results The intervention group (n=221) had higher rates of death than controls (n=237) (all cause 17.6% v 11.8%, hazard ratio 1.62 (95% confidence interval 1.00 to 2.64), P=0.05; cardiovascular disease 17.2% v 11.0%, 1.70 (1.03 to 2.80), P=0.04; coronary heart disease 16.3% v 10.1%, 1.74 (1.04 to 2.92), P=0.04). Inclusion of these recovered data in an updated meta-analysis of linoleic acid intervention trials showed non-significant trends toward increased risks of death from coronary heart disease (hazard ratio 1.33 (0.99 to 1.79); P=0.06) and cardiovascular disease (1.27 (0.98 to 1.65); P=0.07).
Conclusions Advice to substitute polyunsaturated fats for saturated fats is a key component of worldwide dietary guidelines for coronary heart disease risk reduction. However, clinical benefits of the most abundant polyunsaturated fatty acid, omega 6 linoleic acid, have not been established. In this cohort, substituting dietary linoleic acid in place of saturated fats increased the rates of death from all causes, coronary heart disease, and cardiovascular disease. An updated meta-analysis of linoleic acid intervention trials showed no evidence of cardiovascular benefit. These findings could have important implications for worldwide dietary advice to substitute omega 6 linoleic acid, or polyunsaturated fats in general, for saturated fats.
Trial registration Clinical trials NCT01621087.
C1 [Ramsden, Christopher E.; Majchrzak-Hong, Sharon F.; Ringel, Amit; Hibbeln, Joseph R.] NIAAA, Lab Membrane Biophys & Biochem, NIH, Bethesda, MD 20892 USA.
[Ramsden, Christopher E.; Zamora, Daisy; Faurot, Keturah R.] Univ N Carolina, Sch Med, Dept Phys Med & Rehabil, Chapel Hill, NC USA.
[Leelarthaepin, Boonseng] Univ New S Wales, Sydney, NSW, Australia.
[Suchindran, Chirayath M.] Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA.
[Davis, John M.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA.
RP Ramsden, CE (reprint author), NIAAA, Lab Membrane Biophys & Biochem, NIH, Bethesda, MD 20892 USA.
EM Chris.Ramsden@nih.gov
FU Life Insurance Medical Research Fund of Australia; Life Insurance
Medical Research Fund of New Zealand; Intramural Program of the National
Institute on Alcohol Abuse and Alcoholism
FX All authors have completed the ICMJE uniform disclosure form at
www.icmje.org/coi_disclosure.pdf (available on request from the
corresponding author) and declare: support from the Life Insurance
Medical Research Fund of Australia and New Zealand and the Intramural
Program of the National Institute on Alcohol Abuse and Alcoholism for
the submitted work; no financial relationships with any organizations
that might have an interest in the submitted work in the previous three
years; no other relationships or activities that could appear to have
influenced the submitted work.
NR 81
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U1 6
U2 65
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BMJ-BRIT MED J
JI BMJ-British Medical Journal
PD FEB 5
PY 2013
VL 346
AR e8707
DI 10.1136/bmj.e8707
PG 18
WC Medicine, General & Internal
SC General & Internal Medicine
GA 088AR
UT WOS:000314806700001
PM 23386268
ER
PT J
AU Klimuk, E
Akulenko, N
Makarova, KS
Ceyssens, PJ
Volchenkov, I
Lavigne, R
Severinov, K
AF Klimuk, Evgeny
Akulenko, Natalia
Makarova, Kira S.
Ceyssens, Pieter-Jan
Volchenkov, Ivan
Lavigne, Rob
Severinov, Konstantin
TI Host RNA polymerase inhibitors encoded by phi KMV-like phages of
pseudomonas
SO VIROLOGY
LA English
DT Article
DE Bacteriophages T7 and phi KMV; Pseudomonas; RNA polymerase; RNA
polymerase inhibitor
ID COMPLETE GENOMIC SEQUENCE; DNA RESTRICTION SYSTEM; GENE 2 PROTEIN;
ESCHERICHIA-COLI; BACTERIOPHAGE T7; IN-VITRO; TRANSCRIPTION;
PURIFICATION; INITIATION; TRANSLOCATION
AB Escherichia coli bacteriophage T7 is a founding member of a large clade of podoviruses encoding a single-subunit RNA polymerase (RNAP). Phages of the family rely on host RNAP for transcription of early viral genes; viral RNAP transcribes non-early viral genes. T7 and its close relatives encode an inhibitor of host RNAP, the gp2 protein. Gp2 is essential for phage development and ensures that host RNAP does not interfere with viral RNAP transcription at late stages of infection. Here, we identify host RNAP inhibitors encoded by a subset of T7 clade phages related to phi KMV phage of Pseudomonas aeruginosa. We demonstrate that these proteins are functionally identical to T7 gp2 in vivo and in vitro. The ability of some Pseudomonas phage gp2-like proteins to inhibit RNAP is modulated by N-terminal domains, which are absent from the T7 phage homolog. This finding indicates that Pseudomonas phages may use external or internal cues to initiate inhibition of host RNAP transcription and that gp2-like proteins from these phages may be receptors of these cues. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Klimuk, Evgeny; Akulenko, Natalia; Severinov, Konstantin] Russian Acad Sci, Inst Mol Genet, Moscow 123182, Russia.
[Klimuk, Evgeny; Akulenko, Natalia; Severinov, Konstantin] Russian Acad Sci, Inst Gene Biol, Moscow, Russia.
[Klimuk, Evgeny; Volchenkov, Ivan; Severinov, Konstantin] Evrogen JSC, Moscow 117997, Russia.
[Makarova, Kira S.] NIH, Natl Ctr Biotechnol Informat, NLM, Bethesda, MD 20894 USA.
[Ceyssens, Pieter-Jan; Lavigne, Rob] Katholieke Univ Leuven, Biosyst Dept, Lab Gene Technol, Louvain, Belgium.
[Severinov, Konstantin] Rutgers State Univ, Waksman Inst Microbiol, Piscataway, NJ 08854 USA.
[Severinov, Konstantin] Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA.
RP Severinov, K (reprint author), Rutgers State Univ, Waksman Inst, 190 Frelinghuysen Rd, Piscataway, NJ 08854 USA.
EM severik@waksman.rutgers.edu
RI Severinov, Konstantin/C-8545-2016; Klimuk, Evgeny/E-5920-2017
OI Klimuk, Evgeny/0000-0001-5314-038X
FU NIH [GM59295]; Russian Academy of Sciences Presidium; Federal Program
"Scientific and scientific-pedagogical personnel of innovative Russia";
Ministry of education and science of the Russian Federation
[02.740.11.0771, 16.740.11.0748]; Russian Foundation of Basic Research
[12-04-01600-a, P1166]; SBO of the IWT Vlaanderen [IWT 100042]; FWO
Vlaanderen; Department of Health and Human Services intramural program
(NIH, National Library of Medicine)
FX This work was partially supported by NIH grant GM59295, a grant from
Program "Molecular and Cellular Biology" of the Russian Academy of
Sciences Presidium and Federal Program "Scientific and
scientific-pedagogical personnel of innovative Russia 2009-2013", state
contract 02.740.11.0771 and contract no. 16.740.11.0748 from the
Ministry of education and science of the Russian Federation to KS. NA
was partially supported by the Russian Foundation of Basic Research
12-04-01600-a and state contract no.P1166. Work in the RL laboratory was
supported by the SBO grant 'IWT 100042' of the IWT Vlaanderen. PJC holds
a postdoctoral fellowship of the FWO Vlaanderen. KSM is supported by the
Department of Health and Human Services intramural program (NIH,
National Library of Medicine).
NR 36
TC 7
Z9 7
U1 1
U2 16
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD FEB 5
PY 2013
VL 436
IS 1
BP 67
EP 74
DI 10.1016/j.virol.2012.10.021
PG 8
WC Virology
SC Virology
GA 077BV
UT WOS:000314003800008
PM 23127595
ER
PT J
AU Ilinskaya, A
Derse, D
Hill, S
Princler, G
Heidecker, G
AF Ilinskaya, Anna
Derse, David
Hill, Shawn
Princler, Gerald
Heidecker, Gisela
TI Cell-cell transmission allows human T-lymphotropic virus 1 to circumvent
tetherin restriction
SO VIROLOGY
LA English
DT Article
DE HTLV-1; Tetherin; Cell-cell transmission; Virological synapse
ID VIROLOGICAL SYNAPSES; HIV-INFECTION; TYPE-1; VPU; SPREAD; GENE; RELEASE;
HTLV-1; RETROTRANSPOSITION; LYMPHOCYTES
AB Tetherin is part of the cellular innate immunity and impedes cell-free transmission of viruses that bud from the plasma membrane by retaining them on the cell surface. Some viruses have evolved activities in different proteins such as Vpu (HIV-1), K-protein (KSHV), Nef (SIV) or Env (HIV-2) to downregulate tetherin and overcome its restriction. We found that chronically HTLV-1 infected T-cell lines express eightfold more tetherin than uninfected transformed T-cell lines suggesting that tetherin expression is not inhibited by the virus. We observed that even small amounts of exogenous tetherin caused the retention of HTLV-1 on the cell surface and severely reduced cell-free infectivity of HTLV-1, but that cell-cell transmission, which is more relevant for HTLV-1, was significantly less decreased. However, knock-down of tetherin expresssion resulted in a slight increase in cell-cell infection indicating that the protein does not enhance this route of transmission. Published by Elsevier Inc.
C1 [Ilinskaya, Anna; Derse, David; Hill, Shawn; Princler, Gerald; Heidecker, Gisela] Frederick Natl Lab Canc Res, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Heidecker, G (reprint author), Frederick Natl Lab Canc Res, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM ilinskaa@mail.nih.gov; hillshaw@mail.nih.gov; jerryprin@comcast.net;
heidecke@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX We are thankful to Dr. M. Mitchell for help with writing this manuscript
and Dr. Stephen Hughes for helpful discussions. We thank Dr. P. Bieniasz
for the generous gift of the tetherin plasmids. The rabbit anti-tetherin
antiserum was obtained through the AIDS Research and Reference Reagent
Program, Division of AIDS, NIAID, NIH: Anti-Bst-2 (cat# 11722) from Drs.
Klaus Strebel and Amy Andrew. We thank Pat Lloyd for help with plasmid
constructions. This work was supported by the Intramural Research
Program of the National Institutes of Health, National Cancer Institute,
Center for Cancer Research. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does the mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
NR 70
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U1 0
U2 7
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 FEB 5
PY 2013
VL 436
IS 1
BP 201
EP 209
DI 10.1016/j.virol.2012.11.012
PG 9
WC Virology
SC Virology
GA 077BV
UT WOS:000314003800023
PM 23260108
ER
PT J
AU Groffen, DAI
Koster, A
Bosma, H
van den Akker, M
Aspelund, T
Siggeirsdottir, K
Kempen, GIJM
van Eijk, JTM
Eiriksdottir, G
Jonsson, PV
Launer, LJ
Gudnason, V
Harris, TB
AF Groffen, Danielle A. I.
Koster, Annemarie
Bosma, Hans
van den Akker, Marjan
Aspelund, Thor
Siggeirsdottir, Kristin
Kempen, Gertrudis I. J. M.
van Eijk, Jacques Th M.
Eiriksdottir, Gudny
Jonsson, Palmi V.
Launer, Lenore J.
Gudnason, Vilmundur
Harris, Tamara B.
CA Age Gene Environm Susceptibility-R
TI Socioeconomic factors from midlife predict mobility limitation and
depressed mood three decades later; Findings from the AGES-Reykjavik
Study
SO BMC PUBLIC HEALTH
LA English
DT Article
DE Socioeconomic status; Mobility limitation; Depressed mood; Midlife; Old
age
ID HOUSING TENURE; CAR ACCESS; HEALTH; INCOME
AB Background: Taking into account our rapidly ageing population, older people are of particular interest in studying health inequalities. Most studies of older persons only include measures of current socioeconomic status (SES) and do not take into account data from earlier stages of life. In addition, only classic SES measures are used, while alternative measures, such as car ownership and house ownership, might equally well predict health. The present study aims to examine the effect of midlife socioeconomic factors on mobility limitation and depressed mood three decades later.
Methods: Data were from 4,809 men and women aged 33-65 years who participated in the Reykjavik Study (1967-1992) and who were re-examined in old age in the Age, Gene/Environment Susceptibility (AGES) -Reykjavik Study (2002-2006).
Results: Education and occupation predicted mobility limitation and depressed mood. Independently, home and car ownership and the availability of housing features predicted mobility limitation. Shortages of food in childhood and lack of a car in midlife predicted depressed mood.
Conclusion: Socioeconomic factors from midlife and from childhood affect mobility limitation and depressed mood in old age. Prevention of health problems in old age should begin as early as midlife.
C1 [Groffen, Danielle A. I.; Koster, Annemarie; Bosma, Hans; van Eijk, Jacques Th M.] Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care, Dept Social Med, NL-6200 MD Maastricht, Netherlands.
[van den Akker, Marjan] Maastricht Univ, Sch Publ Hlth & Primary Care CAPHRI, Dept Gen Practice, NL-6200 MD Maastricht, Netherlands.
[van den Akker, Marjan] Katholieke Univ Leuven, Dept Gen Practice, Louvain, Belgium.
[Aspelund, Thor; Siggeirsdottir, Kristin; Eiriksdottir, Gudny; Jonsson, Palmi V.; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Aspelund, Thor; Eiriksdottir, Gudny; Jonsson, Palmi V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Kempen, Gertrudis I. J. M.] Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care, Dept Hlth Serv Res, NL-6200 MD Maastricht, Netherlands.
[Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
RP Groffen, DAI (reprint author), Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care, Dept Social Med, POB 616, NL-6200 MD Maastricht, Netherlands.
EM D.Groffen@maastrichtuniversity.nl
RI Aspelund, Thor/C-5983-2008; Koster, Annemarie/E-7438-2010; Gudnason,
Vilmundur/K-6885-2015; Kempen, Gertrudis/H-5978-2016; Bosma,
Hans/A-6184-2013
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084; Kempen, Gertrudis/0000-0002-7053-2198;
FU NIH [N01-AG-12100]; NIA Intramural Research Program; Hjartavernd (the
Icelandic Heart Association); Althingi (the Icelandic Parliament)
FX The Age, Gene/Environment Susceptibility Reykjavik Study is funded by
NIH contract N01-AG-12100, the NIA Intramural Research Program,
Hjartavernd (the Icelandic Heart Association), and the Althingi (the
Icelandic Parliament). The researchers are indebted to the participants
for their willingness to participate in the study.
NR 24
TC 7
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U1 0
U2 9
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 FEB 4
PY 2013
VL 13
AR 101
DI 10.1186/1471-2458-13-101
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 128HQ
UT WOS:000317760400001
PM 23379351
ER
PT J
AU Salive, ME
AF Salive, Marcel E.
TI Multimorbidity in Older Adults
SO EPIDEMIOLOGIC REVIEWS
LA English
DT Article
DE aged; chronic disease; comorbidity; prevalence
ID MULTIPLE CHRONIC CONDITIONS; CHRONIC DISEASE; UNITED-STATES;
RISK-FACTORS; PREVALENCE; HEALTH; COMORBIDITY; POPULATION; DISABILITY;
MORBIDITY
AB Multimorbidity, the coexistence of 2 or more chronic conditions, has become prevalent among older adults as mortality rates have declined and the population has aged. We examined population-based administrative claims data indicating specific health service delivery to nearly 31 million Medicare fee-for-service beneficiaries for 15 prevalent chronic conditions. A total of 67% had multimorbidity, which increased with age, from 50% for persons under age 65 years to 62% for those aged 65-74 years and 81.5% for those aged >= 85 years. A systematic review identified 16 other prevalence studies conducted in community samples that included older adults, with median prevalence of 63% and a mode of 67%. Prevalence differences between studies are probably due to methodological biases; no studies were comparable. Key methodological issues arise from elements of the case definition, including type and number of chronic conditions included, ascertainment methods, and source population. Standardized methods for measuring multimorbidity are needed to enable public health surveillance and prevention. Multimorbidity is associated with elevated risk of death, disability, poor functional status, poor quality of life, and adverse drug events. Additional research is needed to develop an understanding of causal pathways and to further develop and test potential clinical and population interventions targeting multimorbidity.
C1 [Salive, Marcel E.] NIA, Bethesda, MD 20892 USA.
RP Salive, ME (reprint author), NIA, Geriatr Branch, Div Geriatr & Clin Gerontol, 7201 Wisconsin Ave,Suite 3C307, Bethesda, MD 20892 USA.
EM saliveme@nia.nih.gov
NR 44
TC 98
Z9 101
U1 5
U2 34
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0193-936X
J9 EPIDEMIOL REV
JI Epidemiol. Rev.
PD FEB 4
PY 2013
VL 35
SI SI
BP 75
EP 83
DI 10.1093/epirev/mxs009
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 100LT
UT WOS:000315703400007
PM 23372025
ER
PT J
AU Newman, AB
Murabito, JM
AF Newman, Anne B.
Murabito, Joanne M.
TI The Epidemiology of Longevity and Exceptional Survival
SO EPIDEMIOLOGIC REVIEWS
LA English
DT Article
DE aging; exome; genetics; genome; longevity
ID GENOME-WIDE ASSOCIATION; CAUSE-SPECIFIC MORTALITY; DENSITY-LIPOPROTEIN
CHOLESTEROL; LONG-LIVED INDIVIDUALS; MIDLIFE RISK-FACTORS; ALL-CAUSE
MORTALITY; 37-YEAR FOLLOW-UP; MIDDLE-AGED MEN; GROWTH-FACTOR-I;
LIFE-SPAN
AB The field of the "epidemiology of longevity" has been expanding rapidly in recent years. Several long-term cohort studies have followed older adults long enough to identify the most long-lived and to define many factors that lead to a long life span. Very long-lived people such as centenarians have been examined using case-control study designs. Both cohort and case-control studies have been the subject of genome-wide association studies that have identified genetic variants associated with longevity. With growing recognition of the importance of rare variations, family studies of longevity will be useful. Most recently, exome and whole-genome sequencing, gene expression, and epigenetic studies have been undertaken to better define functional variation and regulation of the genome. In this review, we consider how these studies are leading to a deeper understanding of the underlying biologic pathways to longevity.
C1 [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Newman, Anne B.] Univ Pittsburgh, Div Geriatr Med, Sch Med, Pittsburgh, PA 15261 USA.
[Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Newman, AB (reprint author), Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, A529 Crabtree Hall,130 DeSoto St, Pittsburgh, PA 15261 USA.
EM newmana@edc.pitt.edu
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
FU National Institutes of Health [U01 AG023744, R01 AG023629, R01 AG029451]
FX This work was supported by National Institutes of Health grants U01
AG023744, R01 AG023629 (Anne B. Newman), and R01 AG029451 (Joanne M.
Murabito).
NR 128
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U1 1
U2 32
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0193-936X
J9 EPIDEMIOL REV
JI Epidemiol. Rev.
PD FEB 4
PY 2013
VL 35
SI SI
BP 181
EP 197
DI 10.1093/epirev/mxs013
PG 17
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 100LT
UT WOS:000315703400014
PM 23372024
ER
PT J
AU Moreno-Macias, H
Dockery, DW
Schwartz, J
Gold, DR
Laird, NM
Sienra-Monge, JJ
Del Rio-Navarro, BE
Ramirez-Aguilar, M
Barraza-Villarreal, A
Li, HL
London, SJ
Romieu, I
AF Moreno-Macias, Hortensia
Dockery, Douglas W.
Schwartz, Joel
Gold, Diane R.
Laird, Nan M.
Sienra-Monge, Juan J.
Del Rio-Navarro, Blanca E.
Ramirez-Aguilar, Matiana
Barraza-Villarreal, Albino
Li, Huiling
London, Stephanie J.
Romieu, Isabelle
TI Ozone exposure, vitamin C intake, and genetic susceptibility of
asthmatic children in Mexico City: a cohort study
SO RESPIRATORY RESEARCH
LA English
DT Article
DE Air pollution; Asthmatic children; Antioxidant genes; Mexico City;
Vitamin C
ID S-TRANSFERASE P1; LUNG-FUNCTION; CHILDHOOD ASTHMA; AIR-POLLUTION;
ANTIOXIDANT SUPPLEMENTATION; RESPIRATORY HEALTH; OXIDATIVE STRESS;
SCHOOL-CHILDREN; YOUNG-ADULTS; RISK-FACTORS
AB Background: We previously reported that asthmatic children with GSTM1 null genotype may be more susceptible to the acute effect of ozone on the small airways and might benefit from antioxidant supplementation. This study aims to assess the acute effect of ozone on lung function (FEF25-75) in asthmatic children according to dietary intake of vitamin C and the number of putative risk alleles in three antioxidant genes: GSTM1, GSTP1 (rs1695), and NQO1 (rs1800566).
Methods: 257 asthmatic children from two cohort studies conducted in Mexico City were included. Stratified linear mixed models with random intercepts and random slopes on ozone were used. Potential confounding by ethnicity was assessed. Analyses were conducted under single gene and genotype score approaches.
Results: The change in FEF25-75 per interquartile range (60 ppb) of ozone in persistent asthmatic children with low vitamin C intake and GSTM1 null was -91.2 ml/s (p = 0.06). Persistent asthmatic children with 4 to 6 risk alleles and low vitamin C intake showed an average decrement in FEF25-75 of 97.2 ml/s per 60 ppb of ozone (p = 0.03). In contrast in children with 1 to 3 risk alleles, acute effects of ozone on FEF25-75 did not differ by vitamin C intake.
Conclusions: Our results provide further evidence that asthmatic children predicted to have compromised antioxidant defense by virtue of genetic susceptibility combined with deficient antioxidant intake may be at increased risk of adverse effects of ozone on pulmonary function.
C1 [Moreno-Macias, Hortensia; Del Rio-Navarro, Blanca E.] Univ Autonoma Metropolitana, Unidad Iztapalapa, Mexico City 09430, DF, Mexico.
[Dockery, Douglas W.; Schwartz, Joel; Gold, Diane R.] Harvard Univ, Sch Med, Dept Environm Hlth, Boston, MA USA.
[Laird, Nan M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Sienra-Monge, Juan J.; Del Rio-Navarro, Blanca E.] Hosp Infantil Federico Gomez, Mexico City, DF, Mexico.
[Ramirez-Aguilar, Matiana] Comis Fed Protecc Riesgos Sanitarios, SSA, Mexico City, DF, Mexico.
[Barraza-Villarreal, Albino] Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico.
[Li, Huiling; London, Stephanie J.] NIEHS, US Dept Hlth & Human Serv, Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
[Romieu, Isabelle] Int Agcy Res Canc, F-69372 Lyon, France.
RP Moreno-Macias, H (reprint author), Univ Autonoma Metropolitana, Unidad Iztapalapa, Ave San Rafael Atlixco 186,Edificio H-001, Mexico City 09430, DF, Mexico.
EM hmm@xanum.uam.mx
OI London, Stephanie/0000-0003-4911-5290
FU National Council on Science and Technology, in Mexico [26206-M,
38911-M]; Division of Intramural Research, National Institutes of
Health, U.S. Department of Health and Human Services [ZO1 ES 49019, ES
25045]; National Institute of Mental Health
FX The authors thank the children who took part in the study and Irma Lara
who carried out the field work. This work was supported in part by the
National Council on Science and Technology (26206-M, 38911-M), in
Mexico, and the Division of Intramural Research, National Institutes of
Health, U.S. Department of Health and Human Services (ZO1 ES 49019, ES
25045). The National Institute of Mental Health supported Dr Laird.
NR 38
TC 11
Z9 12
U1 1
U2 12
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-993X
J9 RESP RES
JI Respir. Res.
PD FEB 4
PY 2013
VL 14
AR 14
DI 10.1186/1465-9921-14-14
PG 10
WC Respiratory System
SC Respiratory System
GA 098ZA
UT WOS:000315586400001
PM 23379631
ER
PT J
AU Suwannasai, N
Martin, MP
Phosri, C
Sihanonth, P
Whalley, AJS
Spouge, JL
AF Suwannasai, Nuttika
Martin, Maria P.
Phosri, Cherdchai
Sihanonth, Prakitsin
Whalley, Anthony J. S.
Spouge, John L.
TI Fungi in Thailand: A Case Study of the Efficacy of an ITS Barcode for
Automatically Identifying Species within the Annulohypoxylon and
Hypoxylon Genera
SO PLOS ONE
LA English
DT Article
ID INTERNAL TRANSCRIBED SPACER; RIBOSOMAL DNA-SEQUENCES; LAND PLANTS;
PHYLOGENETIC-RELATIONSHIPS; IDENTIFICATION; XYLARIACEAE; TAXONOMY;
NUCLEAR; ALGORITHMS; EVOLUTION
AB Thailand, a part of the Indo-Burma biodiversity hotspot, has many endemic animals and plants. Some of its fungal species are difficult to recognize and separate, complicating assessments of biodiversity. We assessed species diversity within the fungal genera Annulohypoxylon and Hypoxylon, which produce biologically active and potentially therapeutic compounds, by applying classical taxonomic methods to 552 teleomorphs collected from across Thailand. Using probability of correct identification (PCI), we also assessed the efficacy of automated species identification with a fungal barcode marker, ITS, in the model system of Annulohypoxylon and Hypoxylon. The 552 teleomorphs yielded 137 ITS sequences; in addition, we examined 128 GenBank ITS sequences, to assess biases in evaluating a DNA barcode with GenBank data. The use of multiple sequence alignment in a barcode database like BOLD raises some concerns about non-protein barcode markers like ITS, so we also compared species identification using different alignment methods. Our results suggest the following. (1) Multiple sequence alignment of ITS sequences is competitive with pairwise alignment when identifying species, so BOLD should be able to preserve its present bioinformatics workflow for species identification for ITS, and possibly therefore with at least some other non-protein barcode markers. (2) Automated species identification is insensitive to a specific choice of evolutionary distance, contributing to resolution of a current debate in DNA barcoding. (3) Statistical methods are available to address, at least partially, the possibility of expert misidentification of species. Phylogenetic trees discovered a cryptic species and strongly supported monophyletic clades for many Annulohypoxylon and Hypoxylon species, suggesting that ITS can contribute usefully to a barcode for these fungi. The PCIs here, derived solely from ITS, suggest that a fungal barcode will require secondary markers in Annulohypoxylon and Hypoxylon, however. The URL http://tinyurl.com/spouge-barcode contains computer programs and other supplementary material relevant to this article.
C1 [Suwannasai, Nuttika] Srinakharinwirot Univ, Fac Sci, Dept Biol, Bangkok, Thailand.
[Martin, Maria P.] Real Jardin Botan CSIC, Dept Mycol, Madrid, Spain.
[Phosri, Cherdchai] Pibulsongkram Rajabhat Univ, Fac Sci & Technol, Microbiol Programme, Phitsanulok, Thailand.
[Sihanonth, Prakitsin] Chulalongkorn Univ, Fac Sci, Dept Microbiol, Bangkok, Thailand.
[Whalley, Anthony J. S.] Liverpool John Moores Univ, Sch Pharm & Biomol Sci, Liverpool L3 5UX, Merseyside, England.
[Spouge, John L.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Spouge, JL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM spouge@ncbi.nlm.nih.gov
RI phosri, Cherdchai/H-2747-2014; Martin, Maria /H-8069-2012;
OI Martin, Maria /0000-0002-1235-4418; Phosri,
Cherdchai/0000-0003-3963-752X
FU Royal Golden Jubilee Ph.D. Program (RGJ); National Research Council of
Thailand; International Foundation for Science (IFS); British Council;
Liverpool John Moores University; British Mycological Society; Plan
Nacional I+D+I (Ministerio de Ciencia y Tecnologia, Spain)
[REN2002-04068-CO2-01GLO]; Intramural Research Program of the National
Institutes of Health (NIH) (National Library of Medicine, USA)
FX This research was supported in part by the Royal Golden Jubilee Ph.D.
Program (RGJ), National Research Council of Thailand, International
Foundation for Science (IFS), the British Council, Liverpool John Moores
University, the British Mycological Society, the Plan Nacional I+D+I
(REN2002-04068-CO2-01GLO, Ministerio de Ciencia y Tecnologia, Spain),
and the Intramural Research Program of the National Institutes of Health
(NIH) (National Library of Medicine, USA). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 67
TC 7
Z9 8
U1 1
U2 41
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 FEB 4
PY 2013
VL 8
IS 2
AR e54529
DI 10.1371/journal.pone.0054529
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 086NH
UT WOS:000314691100015
PM 23390499
ER
PT J
AU Gray, JJ
Zommer, AE
Bouchard, RJ
Duval, N
Blackstone, C
Linseman, DA
AF Gray, Josie J.
Zommer, Amelia E.
Bouchard, Ron J.
Duval, Nathan
Blackstone, Craig
Linseman, Daniel A.
TI N-terminal cleavage of the mitochondrial fusion GTPase OPA1 occurs via a
caspase-independent mechanism in cerebellar granule neurons exposed to
oxidative or nitrosative stress
SO BRAIN RESEARCH
LA English
DT Article
DE Mitochondrial dynamics; Apoptosis; Aging; Complex I; Reactive oxygen
species; Nitric oxide; Caspase
ID DOMINANT OPTIC ATROPHY; DYNAMIN-RELATED PROTEIN; CYTOCHROME-C RELEASE;
PARKINSONS-DISEASE; NEURODEGENERATIVE DISEASES; PROTEOLYTIC ACTIVATION;
ALZHEIMERS-DISEASE; MAP KINASES; MOUSE MODEL; APOPTOSIS
AB Neuronal cell death via apoptosis or necrosis underlies several devastating neurodegenerative diseases associated with aging. Mitochondrial dysfunction resulting from oxidative or nitrosative stress often acts as an initiating stimulus for intrinsic apoptosis or necrosis. These events frequently occur in conjunction with imbalances in the mitochondrial fission and fusion equilibrium, although the cause and effect relationships remain elusive. Here, we demonstrate in primary rat cerebellar granule neurons (CGNs) that oxidative or nitrosative stress induces an N-terminal cleavage of optic atrophy-1 (OPA1), a dynamin-like GTPase that regulates mitochondrial fusion and maintenance of cristae architecture. This cleavage event is indistinguishable from the N-terminal cleavage of OPA1 observed in CGNs undergoing caspase-mediated apoptosis (Loucks et al., 2009) and results in removal of a key lysine residue (K301) within the GTPase domain. OPA1 cleavage in CGNs occurs coincident with extensive mitochondrial fragmentation, disruption of the microtubule network, and cell death. In contrast to OPA1 cleavage induced in CGNs by removing depolarizing extracellular potassium (5K apoptotic conditions), oxidative or nitrosative stress-induced OPA1 cleavage caused by complex I inhibition or nitric oxide, respectively, is caspase-independent N-terminal cleavage of OPA1 is also observed in vivo in aged rat and mouse midbrain and hippocampal tissues. We conclude that N-terminal cleavage and subsequent inactivation of OPA1 may be a contributing factor in the neuronal cell death processes underlying neurodegenerative diseases, particularly those associated with aging. Furthermore, these data suggest that OPA1 cleavage is a likely convergence point for mitochondrial dysfunction and imbalances in mitochondrial fission and fusion induced by oxidative or nitrosative stress. Published by Elsevier B.V.
C1 [Gray, Josie J.; Zommer, Amelia E.; Duval, Nathan; Linseman, Daniel A.] Univ Denver, Dept Biol Sci, Denver, CO 80208 USA.
[Gray, Josie J.; Zommer, Amelia E.; Duval, Nathan; Linseman, Daniel A.] Univ Denver, Eleanor Roosevelt Inst, Denver, CO 80208 USA.
[Bouchard, Ron J.; Linseman, Daniel A.] Eastern Colorado Hlth Care Syst, Vet Affairs Med Ctr, Denver, CO 80220 USA.
[Blackstone, Craig] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
[Linseman, Daniel A.] Univ Colorado Denver, Div Clin Pharmacol & Toxicol, Aurora, CO 80045 USA.
[Linseman, Daniel A.] Univ Colorado Denver, Neurosci Program, Aurora, CO 80045 USA.
RP Linseman, DA (reprint author), Univ Denver, Dept Biol Sci, 2199 S Univ Blvd, Denver, CO 80208 USA.
EM josie.gray@du.edu; azommer@du.edu; ron.bouchard@ucdenver.edu;
nathan.duval@du.edu; craigblackstc@ninds.nih.gov; daniel.linseman@du.edu
FU NINDS [R01NS062766]; NINDS, NIH
FX Funding was provided by a VA Merit Review Grant and a R01NS062766 grant
from NINDS to D.A.L. and the Intramural Research Program of the NINDS,
NIH to C.B. The authors acknowledge Emily Schroeder, Natalie Kelsey, and
Alexandra Loucks for technical assistance.
NR 72
TC 5
Z9 5
U1 1
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD FEB 4
PY 2013
VL 1494
BP 28
EP 43
DI 10.1016/j.brainres.2012.12.001
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA 084SP
UT WOS:000314559700004
PM 23220553
ER
PT J
AU Migliano, AB
Romero, IG
Metspalu, M
Leavesley, M
Pagani, L
Antao, T
Huang, DW
Sherman, BT
Siddle, K
Scholes, C
Hudjashov, G
Kaitokai, E
Babalu, A
Belatti, M
Cagan, A
Hopkinshaw, B
Shaw, C
Nelis, M
Metspalu, E
Magi, R
Lempicki, RA
Villems, R
Lahr, MM
Kivisild, T
AF Migliano, Andrea Bamberg
Romero, Irene Gallego
Metspalu, Mait
Leavesley, Matthew
Pagani, Luca
Antao, Tiago
Huang, Da-Wei
Sherman, Brad T.
Siddle, Katharine
Scholes, Clarissa
Hudjashov, Georgi
Kaitokai, Elton
Babalu, Avis
Belatti, Maggie
Cagan, Alex
Hopkinshaw, Bryony
Shaw, Colin
Nelis, Mari
Metspalu, Ene
Maegi, Reedik
Lempicki, Richard A.
Villems, Richard
Lahr, Marta Mirazon
Kivisild, Toomas
TI Evolution of the Pygmy Phenotype: Evidence of Positive Selection from
Genome-wide Scans in African, Asian, and Melanesian Pygmies
SO HUMAN BIOLOGY
LA English
DT Article
DE PYGMIES; NEGRITOS; EVOLUTION; PHENOTYPE; GENOTYPE; NATURAL SELECTION;
CONVERGENT ADAPTATION
ID GROWTH-FACTOR-I; MULTILOCUS GENOTYPE DATA; FAMILIAL SHORT STATURE;
HORMONE-RECEPTOR GENE; POPULATION-STRUCTURE; ANDAMAN ISLANDERS;
HUNTER-GATHERERS; ADULT HEIGHT; BROWN FAT; MUTATION
AB Human pygmy populations inhabit different regions of the world, from Africa to Melanesia. In Asia, short-statured populations are often referred to as "negritos." Their short stature has been interpreted as a consequence of thermoregulatory, nutritional, and/or locomotory adaptations to life in tropical forests. A more recent hypothesis proposes that their stature is the outcome of a life history trade-off in high-mortality environments, where early reproduction is favored and, consequently, early sexual maturation and early growth cessation have coevolved. Some serological evidence of deficiencies in the growth hormone/insulin-like growth factor axis have been previously associated with pygmies' short stature. Using genome-wide single-nucleotide polymorphism genotype data, we first tested whether different negrito groups living in the Philippines and Papua New Guinea are closely related and then investigated genomic signals of recent positive selection in African, Asian, and Papuan pygmy populations. We found that negritos in the Philippines and Papua New Guinea are genetically more similar to their nonpygmy neighbors than to one another and have experienced positive selection at different genes. These results indicate that geographically distant pygmy groups are likely to have evolved their short stature independently. We also found that selection on common height variants is unlikely to explain their short stature and that different genes associated with growth, thyroid function, and sexual development are under selection in different pygmy groups.
C1 [Migliano, Andrea Bamberg] UCL, Dept Anthropol, London WC1E 6BT, England.
[Romero, Irene Gallego; Pagani, Luca; Antao, Tiago; Siddle, Katharine; Scholes, Clarissa; Belatti, Maggie; Cagan, Alex; Hopkinshaw, Bryony; Shaw, Colin; Lahr, Marta Mirazon; Kivisild, Toomas] Univ Cambridge, Dept Biol Anthropol, Leverhulme Ctr Human Evolutionary Studies, Cambridge CB2 3DZ, England.
[Metspalu, Mait; Hudjashov, Georgi; Nelis, Mari; Metspalu, Ene; Maegi, Reedik; Villems, Richard; Kivisild, Toomas] Univ Tartu, Dept Evolutionary Biol, EE-50090 Tartu, Estonia.
[Metspalu, Mait; Hudjashov, Georgi; Nelis, Mari; Metspalu, Ene; Maegi, Reedik; Villems, Richard; Kivisild, Toomas] Estonian Bioctr, Tartu, Estonia.
[Leavesley, Matthew] James Cook Univ, Archaeol Dept, Cairns, Australia.
[Huang, Da-Wei; Sherman, Brad T.; Lempicki, Richard A.] NCI, Lab Immunopathogenesis & Bioinformat, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Kaitokai, Elton; Babalu, Avis] Univ Papua New Guinea, Port Moresby, Papua N Guinea.
[Maegi, Reedik] Univ Oxford, Genet & Genom Epidemiol Unit, Wellcome Trust Ctr Human Genet, Oxford, England.
RP Migliano, AB (reprint author), UCL, Dept Anthropol, Mortimer St, London WC1E 6BT, England.
EM a.migliano@ucl.ac.uk
RI Antao, Tiago/C-3615-2009; James Cook University, TESS/B-8171-2012;
Lempicki, Richard/E-1844-2012; Hudjashov, Georgi/H-1254-2015; Metspalu,
Mait/G-8671-2015;
OI Antao, Tiago/0000-0002-7269-5513; Lempicki, Richard/0000-0002-7059-409X;
Metspalu, Mait/0000-0003-3099-9161; Pagani, Luca/0000-0002-6639-524X
FU Clare College fellowship; Newnham Gibbs travel fellowship; Leverhulme
Programme Grant/Hunter-Gatherers Resilience; Natural Environment
Research Council (NERC)/Environmental Factors in the Chronology of Human
Evolution; Dispersal Programme (EFCHED) grant; E.U. European Regional
Development Fund through the Centre of Excellence in Genomics; Estonian
Basic Research grant [SF0182474]; Tartu University grant [PBGMR06901]
FX This project was funded by a Clare College fellowship, a Newnham Gibbs
travel fellowship, and the Leverhulme Programme Grant/Hunter-Gatherers
Resilience to A.B.M.; a Natural Environment Research Council
(NERC)/Environmental Factors in the Chronology of Human Evolution and
Dispersal Programme (EFCHED) grant to M.M.L.; the E.U. European Regional
Development Fund through the Centre of Excellence in Genomics and
Estonian Basic Research grant SF0182474 to R.V.; and Tartu University
grant PBGMR06901 to T.K.
NR 94
TC 22
Z9 22
U1 2
U2 28
PU WAYNE STATE UNIV PRESS
PI DETROIT
PA 4809 WOODWARD AVE, DETROIT, MI 48201-1309 USA
SN 0018-7143
EI 1534-6617
J9 HUM BIOL
JI Hum. Biol.
PD FEB-JUN
PY 2013
VL 85
IS 1-3
SI SI
BP 251
EP 284
PG 34
WC Anthropology; Biology; Genetics & Heredity
SC Anthropology; Life Sciences & Biomedicine - Other Topics; Genetics &
Heredity
GA 259VN
UT WOS:000327554500012
PM 24297229
ER
PT J
AU Hohman, TJ
Peynircioglu, ZF
Beason-Held, LL
AF Hohman, Timothy J.
Peynircioglu, Zehra F.
Beason-Held, Lori L.
TI Flexibility of event boundaries in autobiographical memory
SO MEMORY
LA English
DT Article
DE Autobiographical memory; Ageing; Event; Memory
ID EPISODIC MEMORIES; TIME; PERCEPTION; SEGMENTATION; BEHAVIOR; MODEL; SELF
AB Events have clear and consistent boundaries that are defined during perception in a manner that influences memory performance. The natural process of event segmentation shapes event definitions during perception, and appears to play a critical role in defining distinct episodic memories at encoding. However, the role of retrieval processes in modifying event definitions is not clear. We explored how such processes changed event boundary definitions at recall. In Experiment 1 we showed that distance from encoding is related to boundary flexibility. Participants were more likely to move self-reported event boundaries to include information reported beyond those boundaries when recalling more distant events compared to more recent events. In Experiment 2 we showed that age also influenced boundary flexibility. Older Age adults were more likely to move event boundaries than College Age adults, and the relationship between distance from encoding and boundary flexibility seen in Experiment 1 was present only in College Age and Middle Age adults. These results suggest that factors at retrieval have a direct impact on event definitions in memory and that, although episodic memories may be initially defined at encoding, these definitions are not necessarily maintained in long-term memory.
C1 [Hohman, Timothy J.; Peynircioglu, Zehra F.] Amer Univ, Dept Psychol, Washington, DC 20016 USA.
[Hohman, Timothy J.; Beason-Held, Lori L.] NIA, NIH, Baltimore, MD 21224 USA.
RP Hohman, TJ (reprint author), Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, 519 Light Hall, Nashville, TN 37232 USA.
EM Timothyjhohman@gmail.com
OI Hohman, Timothy/0000-0002-3377-7014
FU Intramural NIH HHS [Z99 AG999999]
NR 33
TC 0
Z9 0
U1 1
U2 6
PU PSYCHOLOGY PRESS
PI HOVE
PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND
SN 0965-8211
EI 1464-0686
J9 MEMORY
JI Memory
PD FEB 1
PY 2013
VL 21
IS 2
BP 249
EP 260
DI 10.1080/09658211.2012.725737
PG 12
WC Psychology, Experimental
SC Psychology
GA 263EW
UT WOS:000327790600008
PM 22989194
ER
PT J
AU Goto, K
Iso, T
Hanaoka, H
Yamaguchi, A
Suga, T
Hattori, A
Irie, Y
Shinagawa, Y
Matsui, H
Syamsunarno, MRAA
Matsui, M
Haque, A
Arai, M
Kunimoto, F
Yokoyama, T
Endo, K
Gonzalez, FJ
Kurabayashi, M
AF Goto, Kosaku
Iso, Tatsuya
Hanaoka, Hirofumi
Yamaguchi, Aiko
Suga, Toshihiro
Hattori, Akinari
Irie, Yasunori
Shinagawa, Yuji
Matsui, Hiroki
Syamsunarno, Mas Rizky A. A.
Matsui, Miki
Haque, Anwarul
Arai, Masashi
Kunimoto, Fumio
Yokoyama, Tomoyuki
Endo, Keigo
Gonzalez, Frank J.
Kurabayashi, Masahiko
TI Peroxisome Proliferator-Activated Receptor-gamma in Capillary Endothelia
Promotes Fatty Acid Uptake by Heart During Long-Term Fasting
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE capillaries; cardiac metabolism; endothelium; fatty acids; transcription
factors
ID PPAR-GAMMA; CD36 DEFICIENCY; BINDING PROTEINS; GENE-EXPRESSION;
ADIPOSE-TISSUE; MICE; MUSCLE; DIFFERENTIATION; TRANSPORT; INSULIN
AB Background-Endothelium is a crucial blood-tissue interface controlling energy supply according to organ needs. We investigated whether peroxisome proliferator-activated receptor-gamma (PPAR gamma) induces expression of fatty acid-binding protein 4 (FABP4) and fatty acid translocase (FAT)/CD36 in capillary endothelial cells (ECs) to promote FA transport into the heart.
Methods and Results-Expression of FABP4 and CD36 was induced by the PPAR gamma agonist pioglitazone in human cardiac microvessel ECs (HCMECs), but not in human umbilical vein ECs. Real-time PCR and immunohistochemistry of the heart tissue of control (Pparg(fl/null)) mice showed an increase in expression of FABP4 and CD36 in capillary ECs by either pioglitazone treatment or 48 hours of fasting, and these effects were not found in mice deficient in endothelial PPAR gamma (Pparg(Delta EC/null)). Luciferase reporter constructs of the Fabp4 and CD36 promoters were markedly activated by pioglitazone in HCMECs through canonical PPAR-responsive elements. Activation of PPAR gamma facilitated FA uptake by HCMECs, which was partially inhibited by knockdown of either FABP4 or CD36. Uptake of an FA analogue, I-125-BMIPP, was significantly reduced in heart, red skeletal muscle, and adipose tissue in Pparg(Delta EC/null) mice as compared with Pparg(fl/null) mice after olive oil loading, whereas those values were comparable between Pparg(fl/null) and Pparg(Delta EC/null) null mice on standard chow and a high-fat diet. Furthermore, Pparg(Delta EC/null) mice displayed slower triglyceride clearance after olive oil loading.
Conclusions-These findings identified a novel role for capillary endothelial PPAR gamma as a regulator of FA handing in FA-metabolizing organs including the heart in the postprandial state after long-term fasting.
C1 [Iso, Tatsuya; Kurabayashi, Masahiko] Gunma Univ, Grad Sch Hlth Sci, Educ & Res Support Ctr, Maebashi, Gumma 371, Japan.
[Goto, Kosaku; Iso, Tatsuya; Suga, Toshihiro; Matsui, Hiroki; Syamsunarno, Mas Rizky A. A.; Matsui, Miki; Arai, Masashi; Kurabayashi, Masahiko] Gunma Univ, Grad Sch Hlth Sci, Dept Med & Biol Sci, Maebashi, Gumma 371, Japan.
[Hanaoka, Hirofumi; Yamaguchi, Aiko] Gunma Univ, Grad Sch Hlth Sci, Dept Bioimaging Informat Anal, Maebashi, Gumma 371, Japan.
[Endo, Keigo] Gunma Univ, Grad Sch Hlth Sci, Dept Diagnost Radiol & Nucl Med, Maebashi, Gumma 371, Japan.
[Haque, Anwarul; Kunimoto, Fumio] Gunma Univ, Grad Sch Hlth Sci, Dept Anesthesiol & Intens Care Med, Maebashi, Gumma 371, Japan.
[Hattori, Akinari; Irie, Yasunori; Shinagawa, Yuji; Matsui, Hiroki; Yokoyama, Tomoyuki] Gunma Univ, Grad Sch Med, Lab Sci, Maebashi, Gumma 371, Japan.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Iso, T (reprint author), 3-39-22 Showa Machi, Maebashi, Gumma 3718511, Japan.
EM isot@gunma-u.ac.jp
FU Japan Society for the Promotion of Science; Japan Cardiovascular
Foundation; Takeda Science Foundation; Therapeutic Research for
Metabolic Syndrome; AstraZeneca; Vehicle Racing Commemorative Foundation
FX This work was supported, in part, by a Grant-in-Aid for Scientific
Research from the Japan Society for the Promotion of Science (to M. K.
and T. I.), a grant from the Japan Cardiovascular Foundation (to M. K.),
and grants from Takeda Science Foundation, Therapeutic Research for
Metabolic Syndrome, AstraZeneca, and the Vehicle Racing Commemorative
Foundation (to T.I.).
NR 38
TC 11
Z9 11
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD FEB
PY 2013
VL 2
IS 1
AR UNSP e004861
DI 10.1161/JAHA.112.004861
PG 15
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 243SF
UT WOS:000326336800013
PM 23525438
ER
PT J
AU Harford, JB
Aljawi, DM
AF Harford, Joe B.
Aljawi, Deena M.
TI The need for more and better palliative care for Muslim patients
SO PALLIATIVE & SUPPORTIVE CARE
LA English
DT Editorial Material
C1 [Harford, Joe B.] NCI, Bethesda, MD 20892 USA.
[Aljawi, Deena M.] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia.
RP Harford, JB (reprint author), NCI, Bethesda, MD 20892 USA.
NR 1
TC 3
Z9 3
U1 0
U2 2
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1478-9515
J9 PALLIAT SUPPORT CARE
JI Palliat. Support Care
PD FEB
PY 2013
VL 11
IS 1
BP 1
EP 4
DI 10.1017/S1478951512000053
PG 4
WC Health Policy & Services
SC Health Care Sciences & Services
GA 219VP
UT WOS:000324539500001
PM 22874103
ER
PT J
AU Wiener, L
Mcconnell, DG
Latella, L
Ludi, E
AF Wiener, Lori
Mcconnell, Denice Grady
Latella, Lauren
Ludi, Erica
TI Cultural and religious considerations in pediatric palliative care
SO PALLIATIVE & SUPPORTIVE CARE
LA English
DT Article
DE Culture; Pediatric palliative care; Religion; Spirituality; Children;
Ethnicity
ID OF-LIFE CARE; HEALTH-CARE; DECISION-MAKING; PAIN MANAGEMENT; CANCER;
CHILDREN; END; BARRIERS; DEATH; PARENTS
AB Objective: A growing multicultural society presents healthcare providers with a difficult task of providing appropriate care for individuals who have different life experiences, beliefs, value systems, religions, languages, and notions of healthcare. This is especially vital when end-of-life care is needed during childhood. There is a dearth of literature addressing cultural considerations in the pediatric palliative care field. As members of a specific culture often do not ascribe to the same religious traditions, the purpose of this article was to explore and review how culture and religion informs and shapes pediatric palliative care.
Method: Comprehensive literature searches were completed through an online search of nine databases for articles published between 1980 and 2011: PsychINFO, MEDLINE (R), Journal of Citation Reports-Science Edition, Embase, Scopus, CINAHL (R), Social Sciences Citation Index (SSCI), EBSCO, and Ovid. Key terms included: culture, transcultural, spiritual, international, ethnic, customs or religion AND end-of-life, palliative care, death, dying, cancer, or hospice, and children, pediatrics, or pediatric oncology. Reference lists in the retrieved articles were examined for additional studies that fit the inclusion criteria, and relevant articles were included for review. In addition, web-based searches of specific journals were conducted. These included, but were not limited to: Qualitative Health Research, Psycho-Oncology, Journal of Psychosocial Oncology, Journal of Pediatric Psychology, Journal of Pediatric Health Care, Journal of Pediatric Oncology Nursing, Omega, Social Work in Health Care, and Journal of Palliative Medicine.
Results: Thirty-seven articles met eligibility criteria. From these, seven distinct themes emerged that have implications for pediatric palliative care. These include the role of culture in decision-making, faith and the involvement of clergy, communication (spoken and unspoken language), communicating to children about death (truth telling), the meaning of pain and suffering, the meaning of death and dying, and location of end-of-life care.
Significance of results: The review of the literature provides insight into the influence of religion and how culture informs lifestyle and shapes the experiences of illness, pain, and end-of-life care. Recommendations for providing culturally sensitive end-of-life care are offered through the framework outlined in the Initiative for Pediatric Palliative Care Quality Improvement Project of 2002. Cultural traditions are dynamic, never static, and cannot be generalized to all families. Guidelines to aid in approaches to palliative care are provided, and providers are encouraged to define these important differences for each family under their care.
C1 [Wiener, Lori; Latella, Lauren] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Mcconnell, Denice Grady] Adams Hanover Counseling Serv Inc, Hanover, PA USA.
[Latella, Lauren] Cornell Univ, Ithaca, NY USA.
[Ludi, Erica] NIMH, NIH, Bethesda, MD 20892 USA.
RP Wiener, L (reprint author), NCI, NIH, Pediat Clin, 10 Ctr Dr,1-6466, Bethesda, MD 20892 USA.
EM wienerl@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 106
TC 26
Z9 28
U1 7
U2 69
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1478-9515
J9 PALLIAT SUPPORT CARE
JI Palliat. Support Care
PD FEB
PY 2013
VL 11
IS 1
BP 47
EP 67
DI 10.1017/S1478951511001027
PG 21
WC Health Policy & Services
SC Health Care Sciences & Services
GA 219VP
UT WOS:000324539500007
PM 22617619
ER
PT J
AU Falcone, EL
Holland, SM
AF Falcone, E. Liana
Holland, Steven M.
TI Streptococcal Infections in Patients with Chronic Granulomatous Disease:
Case Report and Review of the Literature
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Letter
C1 [Falcone, E. Liana; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, CRC, Bethesda, MD 20892 USA.
RP Falcone, EL (reprint author), NIAID, Lab Clin Infect Dis, NIH, CRC, Rm B3 4141,MSC 1684, Bethesda, MD 20892 USA.
EM emilia.falcone@nih.gov; smh@nih.gov
FU Intramural NIH HHS [Z01 AI000646-16]
NR 2
TC 0
Z9 0
U1 2
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD FEB
PY 2013
VL 33
IS 2
BP 310
EP 310
DI 10.1007/s10875-012-9823-8
PG 1
WC Immunology
SC Immunology
GA 201DX
UT WOS:000323122000004
PM 23108438
ER
PT J
AU Lo, B
Ramaswamy, M
Davis, J
Price, S
Rao, VK
Siegel, RM
Lenardo, MJ
AF Lo, Bernice
Ramaswamy, Madhu
Davis, Joie
Price, Susan
Rao, V. Koneti
Siegel, Richard M.
Lenardo, Michael J.
TI A Rapid Ex Vivo Clinical Diagnostic Assay for Fas Receptor-Induced T
Lymphocyte Apoptosis
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE Apoptosis; Fas; Autoimmune Lymphoproliferative syndrome; diagnosis;
effector memory T cells; double-negative T cells
ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; MUTATIONS; PENETRANCE; COMMON;
CELLS
AB Deleterious mutations in genes involved in the Fas apoptosis pathway lead to Autoimmune Lymphoproliferative Syndrome (ALPS). Demonstration of an apoptosis defect is critical for the diagnosis and study of ALPS. The traditional in vitro apoptosis assay, however, requires a week of experimental procedures. Here, we show that defects in Fas-induced apoptosis in PBMCs can be evaluated directly ex vivo using multicolor flow cytometry to analyze the apoptosis of effector memory T cells, a Fas-sensitive subset of PBMCs. This method allowed us to sensitively quantify defective apoptosis in ALPS patients within a few hours. Some ALPS patients (ALPS-sFAS) without germline mutations have somatic mutations in Fas specifically in double-negative alpha beta T cells (DNTs), an unusual lymphocyte population that is characteristically expanded in ALPS. Since DNTs have been notoriously difficult to culture, defective apoptosis has not been previously demonstrated for ALPS-sFAS patients. Using our novel ex vivo apoptosis assay, we measured Fas-induced apoptosis of DNTs for the first time and found that ALPS-sFAS patients had significant apoptosis defects in these cells compared to healthy controls. Hence, this rapid apoptosis assay can expedite the diagnosis of new ALPS patients, including those with somatic mutations, and facilitate clinical and molecular investigation of these diseases.
C1 [Lo, Bernice; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Ramaswamy, Madhu; Siegel, Richard M.] NIAMSD, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
[Davis, Joie; Price, Susan; Rao, V. Koneti] NIAID, ALPS Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Lenardo, MJ (reprint author), Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA.
EM Lenardo@nih.gov
OI Lo, Bernice/0000-0002-1087-6845
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX We thank the patients and healthy blood donors. We also thank Josh
Milner for use of his LSRFortessa. We thank Julie Niemela for assistance
in mutation nomenclature. We also thank Claire Liu for assay name
recommendations, and we thank Helen Su and Chryssa Kanellopoulou for
critical reading of the manuscript. This research was supported by the
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 23
TC 4
Z9 4
U1 0
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD FEB
PY 2013
VL 33
IS 2
BP 479
EP 488
DI 10.1007/s10875-012-9811-z
PG 10
WC Immunology
SC Immunology
GA 201DX
UT WOS:000323122000024
PM 23054345
ER
PT J
AU La Merrill, M
Emond, C
Kim, MJ
Antignac, JP
Le Bizec, B
Clement, K
Birnbaum, LS
Barouki, R
AF La Merrill, Michele
Emond, Claude
Kim, Min Ji
Antignac, Jean-Philippe
Le Bizec, Bruno
Clement, Karine
Birnbaum, Linda S.
Barouki, Robert
TI Toxicological Function of Adipose Tissue: Focus on Persistent Organic
Pollutants
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Review
DE adipose tissue; aryl hydrocarbon receptor; development; diabetes;
dioxin; inflammation; obesity; obesogens; polychlorinated biphenyls;
toxicity; toxicokinetics
ID ARYL-HYDROCARBON RECEPTOR; ENDOCRINE-DISRUPTING CHEMICALS;
LOW-DENSITY-LIPOPROTEIN; LIPID-METABOLISM; FAT MASS; BODY-FAT;
POLYCHLORINATED-BIPHENYLS; ADIPOCYTE DIFFERENTIATION; LIPOPHILIC
CHEMICALS; PERINATAL EXPOSURE
AB BACKGROUND: Adipose tissue (AT) is involved in several physiological functions, including metabolic regulation, energy storage, and endocrine functions.
OBJECTIVES: In this review we examined the evidence that an additional function of AT is to modulate persistent organic pollutant (POP) toxicity through several mechanisms.
METHODS: We reviewed the literature on the interaction of AT with POPs to provide a comprehensive model for this additional function of AT.
DISCUSSION: As a storage compartment for lipophilic POPs, AT plays a critical role in the toxicokinetics of a variety of drugs and pollutants, in particular, POPs. By sequestering POPs, AT can protect other organs and tissues from POPs overload. However, this protective function could prove to be a threat in the long run. The accumulation of lipophilic POPs will increase total body burden. These accumulated POPs are slowly released into the bloodstream, and more so during weight loss. Thus, AT constitutes a continual source of internal exposure to POPs. In addition to its buffering function, AT is also a target of POPs and may mediate part of their metabolic effects. This is particularly relevant because many POPs induce obesogenic effects that may lead to quantitative and qualitative alterations of AT. Some POPs also induce a proinflammatory state in AT, which may lead to detrimental metabolic effects.
CONCLUSION: AT appears to play diverse functions both as a modulator and as a target of POPs toxicity.
C1 [La Merrill, Michele] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA.
[Emond, Claude] BioSimulat Consulting Inc, Newark, DE USA.
[Emond, Claude] Univ Montreal, Dept Sante Environm & Sante Travail, Montreal, PQ, Canada.
[Kim, Min Ji; Barouki, Robert] INSERM, UMR S 747, Paris, France.
[Kim, Min Ji; Barouki, Robert] Univ Paris 05, Ctr Univ St Peres, F-75270 Paris 06, France.
[Kim, Min Ji; Barouki, Robert] Hop Necker Enfants Malad, Assistance Publ Hop Paris, Paris, France.
[Kim, Min Ji] Univ Paris 13, Sorbonne Paris Cite, INSERM, U698, Bobigny, France.
[Antignac, Jean-Philippe; Le Bizec, Bruno] Atlanpole La Chantrerie, LABERCA, USC INRA 2013, ONIRIS, Nantes, France.
[Clement, Karine] INSERM, U872, Nutriom Equipe 7, Paris, France.
[Clement, Karine] Univ Paris 06, UMR S 872, Ctr Rech Cordeliers, Paris, France.
[Clement, Karine] Hop La Pitie Salpetriere, Assistance Publ Hop Paris, Dept Nutr & Endocrinol, Paris, France.
[Clement, Karine] CRNH Ile France, Paris, France.
[Birnbaum, Linda S.] NCI, Res Triangle Pk, NC USA.
[Birnbaum, Linda S.] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
RP Barouki, R (reprint author), Univ Paris 05, INSERM, UMRS 747, Ctr Univ St Peres, 45 Rue St Peres, F-75270 Paris 06, France.
EM robert.barouki@parisdescartes.fr
RI Tuomisto, Jouko/J-7450-2012;
OI LE BIZEC, Bruno/0000-0002-0600-5895; ANTIGNAC,
Jean-Philippe/0000-0001-9512-9314
FU INSERM (Institut National de la Sante et de la Recherche Medicale);
National Institute of Environmental Health Sciences (NIEHS); Universite
Paris Descartes; Universite Pierre et Marie Curie; INRA (Institut
National de la Recherche Agronomique)
FX This study was funded by INSERM (Institut National de la Sante et de la
Recherche Medicale), the National Institute of Environmental Health
Sciences (NIEHS), the Universite Paris Descartes, the Universite Pierre
et Marie Curie, and INRA (Institut National de la Recherche
Agronomique).
NR 98
TC 46
Z9 47
U1 6
U2 80
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 FEB
PY 2013
VL 121
IS 2
BP 162
EP 169
DI 10.1289/ehp.1205485
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 208SX
UT WOS:000323700900016
PM 23221922
ER
PT J
AU Behl, M
Rao, D
Aagaard, K
Davidson, TL
Levin, ED
Slotkin, TA
Srinivasan, S
Wallinga, D
White, MF
Walker, VR
Thayer, KA
Holloway, AC
AF Behl, Mamta
Rao, Deepa
Aagaard, Kjersti
Davidson, Terry L.
Levin, Edward D.
Slotkin, Theodore A.
Srinivasan, Supriya
Wallinga, David
White, Morris F.
Walker, Vickie R.
Thayer, Kristina A.
Holloway, Alison C.
TI Evaluation of the Association between Maternal Smoking, Childhood
Obesity, and Metabolic Disorders: A National Toxicology Program Workshop
Review
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Review
DE animal; chemically induced/epidemiology; diabetes; environmental
epidemiology; glucose; insulin; maternal smoking toxicity; metabolism;
nicotine toxicity; obesity
ID BODY-MASS INDEX; NEONATAL NICOTINE EXPOSURE; DIABETES-RELATED
AUTOANTIBODIES; ENVIRONMENTAL RISK-FACTORS; PROSPECTIVE BIRTH COHORT;
ADIPOSE-TISSUE FUNCTION; ENZYME GENE-EXPRESSION; BETA-CELL APOPTOSIS;
CORD BLOOD LEPTIN; RAPID WEIGHT-GAIN
AB BACKGROUND: An emerging literature suggests that environmental chemicals may play a role in the development of childhood obesity and metabolic disorders, especially when exposure occurs early in life.
OBJECTIVE: Here we assess the association between these health outcomes and exposure to maternal smoking during pregnancy as part of a broader effort to develop a research agenda to better understand the role of environmental chemicals as potential risk factors for obesity and metabolic disorders.
METHODS: PubMed was searched up to 8 March 2012 for epidemiological and experimental animal studies related to maternal smoking or nicotine exposure during pregnancy and childhood obesity or metabolic disorders at any age. A total of 101 studies-83 in humans and 18 in animals-were identified as the primary literature.
DISCUSSION: Current epidemiological data support a positive association between maternal smoking and increased risk of obesity or overweight in offspring. The data strongly suggest a causal relation, although the possibility that the association is attributable to unmeasured residual confounding cannot be completely ruled out. This conclusion is supported by findings from laboratory animals exposed to nicotine during development. The existing literature on human exposures does not support an association between maternal smoking during pregnancy and type 1 diabetes in offspring. Too few human studies have assessed outcomes related to type 2 diabetes or metabolic syndrome to reach conclusions based on patterns of findings. There may be a number of mechanistic pathways important for the development of aberrant metabolic outcomes following perinatal exposure to cigarette smoke, which remain largely unexplored.
CONCLUSIONS: From a toxicological perspective, the linkages between maternal smoking during pregnancy and childhood overweight/obesity provide proof-of-concept of how early-life exposure to an environmental toxicant can be a risk factor for childhood obesity.
C1 [Behl, Mamta] Kelly Govt Solut, Res Triangle Pk, NC USA.
[Behl, Mamta] Natl Inst Environm Sci NIEHS, Div Natl Toxicol Program, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Rao, Deepa] Integrated Lab Syst Inc, Res Triangle Pk, NC USA.
[Aagaard, Kjersti] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA.
[Davidson, Terry L.] Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA.
[Levin, Edward D.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA.
[Slotkin, Theodore A.] Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC USA.
[Srinivasan, Supriya] Scripps Res Inst, Dept Chem Physiol, La Jolla, CA 92037 USA.
[Wallinga, David] Inst Agr & Trade Policy, Food & Hlth Program, Minneapolis, MN USA.
[White, Morris F.] Childrens Hosp Boston, Howard Hughes Med Inst, Div Endocrinol, Boston, MA USA.
[Walker, Vickie R.; Thayer, Kristina A.] NIEHS, Div Natl Toxicol Program, Off Hlth Assessment & Translat, NIH,DHHS, Res Triangle Pk, NC 27709 USA.
[Holloway, Alison C.] McMaster Univ, Dept Obstet & Gynecol, Reprod Biol Div, Hamilton, ON, Canada.
RP Holloway, AC (reprint author), McMaster Univ, Dept Obstet & Gynecol, HSC 3N52,1280 Main St West, Hamilton, ON L8S 4K1, Canada.
EM hollow@mcmaster.ca
FU National Institute of Environmental Health Sciences/National Toxicology
Program (NIEHS/NTP); U.S. Environmental Protection Agency (EPA); Food
and Drug Administration National Center for Toxicological Research
(FDA/NCTR)
FX This review is based on deliberations that occurred at an 11-13 January
2011 workshop sponsored by the National Institute of Environmental
Health Sciences/National Toxicology Program (NIEHS/NTP), U.S.
Environmental Protection Agency (EPA), and the Food and Drug
Administration National Center for Toxicological Research (FDA/NCTR)
(http://ntp.niehs.nih.gov/go/36433).
NR 144
TC 43
Z9 43
U1 3
U2 39
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 FEB
PY 2013
VL 121
IS 2
BP 170
EP 180
DI 10.1289/ehp.1205404
PG 11
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 208SX
UT WOS:000323700900017
PM 23232494
ER
PT J
AU Louis, GMB
Sundaram, R
Schisterman, EF
Sweeney, AM
Lynch, CD
Gore-Langton, RE
Maisog, J
Kim, S
Chen, Z
Barr, DB
AF Louis, Germaine M. Buck
Sundaram, Rajeshwari
Schisterman, Enrique F.
Sweeney, Anne M.
Lynch, Courtney D.
Gore-Langton, Robert E.
Maisog, Jose
Kim, Sungduk
Chen, Zhen
Barr, Dana B.
TI Persistent Environmental Pollutants and Couple Fecundity: The LIFE Study
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE conception; cotinine; fecundity; organochlorine pesticides;
polybrominated diphenyl ethers; polychlorinated biphenyls;
perfluorochemicals; time to pregnancy
ID ENDOCRINE-DISRUPTING CHEMICALS; MENSTRUAL-CYCLE; HUMAN-SERUM;
POLYCHLORINATED-BIPHENYLS; EXPOSURE MEASUREMENT; DYSGENESIS SYNDROME;
PROSPECTIVE COHORT; REGRESSION-MODELS; PREGNANCY; TIME
AB BACKGROUND: Evidence suggesting that persistent environmental pollutants may be reproductive toxicants underscores the need for prospective studies of couples for whom exposures are measured.
OBJECTIVES: We examined the relationship between selected persistent pollutants and couple fecundity as measured by time to pregnancy.
METHODS: A cohort of 501 couples who discontinued contraception to become pregnant was prospectively followed for 12 months of trying to conceive or until a human chorionic gonadotrophin (hCG) test confirmed pregnancy. Couples completed daily journals on lifestyle and provided biospecimens for the quantification of 9 organochlorine pesticides, 1 polybrominated biphenyl, 10 polybrominated diphenyl ethers, 36 polychlorinated biphenyls (PCBs), and 7 perfluorochemicals (PFCs) in serum. Using Cox models for discrete time, we estimated fecundability odds ratios (FORs) and 95% CIs separately for each partner's concentrations adjusting for age, body mass index, serum cotinine, serum lipids (except for PFCs), and study site (Michigan or Texas); sensitivity models were further adjusted for left truncation or time off of contraception (<= 2 months) before enrollment.
RESULTS: The adjusted reduction in fecundability associated with standard deviation increases in log-transformed serum concentrations ranged between 18% and 21% for PCB congeners 118, 167, 209, and perfluorooctane sulfonamide in females; and between 17% and 29% for p,p'-DDE and PCB congeners 138, 156, 157, 167, 170, 172, and 209 in males. The strongest associations were observed for PCB 167 (FOR 0.79; 95% CI: 0.64, 0.97) in females and PCB 138 (FOR = 0.71; 95% CI: 0.52, 0.98) in males.
CONCLUSIONS: In this couple-based prospective cohort study with preconception enrollment and quantification of exposures in both female and male partners, we observed that a subset of persistent environmental chemicals were associated with reduced fecundity.
C1 [Louis, Germaine M. Buck; Sundaram, Rajeshwari; Schisterman, Enrique F.; Maisog, Jose; Kim, Sungduk; Chen, Zhen] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Sweeney, Anne M.] Texas A&M Hlth Sci Ctr, Sch Rural Publ Hlth, Dept Epidemiol & Biostat, College Stn, TX USA.
[Lynch, Courtney D.] Ohio State Univ, Coll Med, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
[Gore-Langton, Robert E.] EMMES Corp, Rockville, MD USA.
[Barr, Dana B.] Emory Univ, Rollins Sch Publ Hlth, Dept Occupat & Environm Hlth, Atlanta, GA 30322 USA.
RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA.
EM louisg@mail.nih.gov
OI Sundaram, Rajeshwari/0000-0002-6918-5002; Schisterman,
Enrique/0000-0003-3757-641X; Buck Louis, Germaine/0000-0002-1774-4490
FU Intramural Research Program of the NICHD [N01-HD-3-3355, N01-HD-3-3356,
NOH-HD-3-3358]
FX This research was supported by the Intramural Research Program of the
NICHD (contracts N01-HD-3-3355, N01-HD-3-3356, and NOH-HD-3-3358).
NR 61
TC 49
Z9 51
U1 3
U2 28
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 FEB
PY 2013
VL 121
IS 2
BP 231
EP 236
DI 10.1289/ehp.1205301
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 208SX
UT WOS:000323700900026
PM 23151773
ER
PT J
AU Bertelsen, RJ
Carlsen, KCL
Calafat, AM
Hoppin, JA
Haland, G
Mowinckel, P
Carlsen, KH
Lovik, M
AF Bertelsen, Randi J.
Carlsen, Karin C. Lodrup
Calafat, Antonia M.
Hoppin, Jane A.
Haland, Geir
Mowinckel, Petter
Carlsen, Kai-Hakon
Lovik, Martinus
TI Urinary Biomarkers for Phthalates Associated with Asthma in Norwegian
Children
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE asthma; biomarkers; children; endocrine disruptors; phthalates
ID NUTRITION EXAMINATION SURVEY; INTERIOR SURFACE MATERIALS; NEW-YORK-CITY;
METABOLITE LEVELS; NATIONAL-HEALTH; BIRTH COHORT; EXPOSURE; VARIABILITY;
PRODUCTS; OSLO
AB BACKGROUND: High-molecular-weight phthalates in indoor dust have been associated with asthma in children, but few studies have evaluated phthalate biomarkers in association with respiratory outcomes.
OBJECTIVES: We explored the association between urinary concentrations of phthalate metabolites and current asthma.
METHODS: In a cross-sectional analysis, 11 metabolites of 8 phthalates [including four metabolites of di(2-ethylhexyl) phthalate] were measured in one first morning void collected from 2001 through 2004 from 623 10-year-old Norwegian children. Logistic regression models controlling for urine specific gravity, sex, parental asthma, and income were used to estimate associations between current asthma and phthalate metabolite concentrations by quartiles or as log(10)-transformed variables.
RESULTS: Current asthma was associated with both mono(carboxyoctyl) phthalate (MCOP) and mono(carboxynonyl) phthalate (MCNP), although the association was limited to those in the highest quartile of these chemicals. The adjusted odds ratio (aOR) for current asthma was 1.9 (95% CI: 1.0, 3.3) for the highest MCOP quartile compared with the lowest quartile, and 1.3 (95% CI: 0.98, 1.7) for an interquartile-range increase. The aOR for current asthma was 2.2 (95% CI: 1.2, 4.0) for the highest MCNP quartile and 1.3 (95% CI: 1.0, 1.7) for an interquartile-range increase. The other phthalate metabolites were not associated with current asthma.
CONCLUSIONS: Current asthma was associated with the highest quartiles of MCOP and MCNP, metabolites of two high molecular weight phthalates, diisononyl phthalate and diisodecyl phthalate, respectively. Given the short biological half-life of the phthalates and the cross-sectional design, our findings should be interpreted cautiously.
C1 [Bertelsen, Randi J.; Lovik, Martinus] Norwegian Inst Publ Hlth, Dept Food Water & Cosmet, N-0403 Oslo, Norway.
[Bertelsen, Randi J.; Hoppin, Jane A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Carlsen, Karin C. Lodrup; Haland, Geir; Mowinckel, Petter; Carlsen, Kai-Hakon] Oslo Univ Hosp, Dept Pediat, Oslo, Norway.
[Carlsen, Karin C. Lodrup; Haland, Geir; Carlsen, Kai-Hakon] Univ Oslo, Fac Med, Oslo, Norway.
[Calafat, Antonia M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA.
RP Bertelsen, RJ (reprint author), Norwegian Inst Publ Hlth, Dept Food Water & Cosmet, POB 4404 Nydalen, N-0403 Oslo, Norway.
EM randi.jacobsen.bertelsen@fhi.no
FU Norwegian Institute of Public Health; Research Council of Norway; Oslo
University Hospital; Intramural Research Program of the National
Institutes of Health (NIH), National Institute of Environmental Health
Sciences (NIEHS); AstraZeneca Norway; Sixth EU Framework program for
research [FOOD-CT-2004-506378]
FX The study was funded by the Norwegian Institute of Public Health,
Research Council of Norway, and Oslo University Hospital, and supported
in part by the Intramural Research Program of the National Institutes of
Health (NIH), National Institute of Environmental Health Sciences
(NIEHS). An unrestricted grant from the AstraZeneca Norway fund for
research within pulmonology was given in 2006 to G.H. for the cost of
phthalate analyses in urine. The sponsor had no influence on the
analyses, interpretation, or presentation. The study was performed
within ORAACLE (the Oslo Research Group of Asthma and Allergy in
Childhood: the Lung and Environment), a member of GA2LEN (Global Allergy
and Asthma European Network), supported by the Sixth EU Framework
program for research, contract FOOD-CT-2004-506378.
NR 38
TC 40
Z9 40
U1 6
U2 39
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 FEB
PY 2013
VL 121
IS 2
BP 251
EP 256
DI 10.1289/ehp.1205256
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 208SX
UT WOS:000323700900029
PM 23164678
ER
PT J
AU Guha, N
Ward, MH
Gunier, R
Colt, JS
Lea, CS
Buffler, PA
Metayer, C
AF Guha, Neela
Ward, Mary H.
Gunier, Robert
Colt, Joanne S.
Lea, C. Suzanne
Buffler, Patricia A.
Metayer, Catherine
TI Characterization of Residential Pesticide Use and Chemical Formulations
through Self-Report and Household Inventory: The Northern California
Childhood Leukemia Study
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE exposure assessment; pesticides; population-based study; residential
pesticide use; US EPA
ID NON-HODGKIN-LYMPHOMA; EXPOSURES; CANCER; RISK; CHILDRENS; HOME
AB BACKGROUND: Home and garden pesticide use has been linked to cancer and other health outcomes in numerous epidemiological studies. Exposure has generally been self-reported, so the assessment is potentially limited by recall bias and lack of information on specific chemicals.
OBJECTIVES: As part of an integrated assessment of residential pesticide exposure, we identified active ingredients and described patterns of storage and use.
METHODS: During a home interview of 500 residentially stable households enrolled in the Northern California Childhood Leukemia Study during 2001-2006, trained interviewers inventoried residential pesticide products and queried participants about their storage and use. U.S. Environmental Protection Agency registration numbers, recorded from pesticide product labels, and pesticide chemical codes were matched to public databases to obtain information on active ingredients and chemical class. Poisson regression was used to identify independent predictors of pesticide storage. Analyses were restricted to 259 participating control households.
RESULTS: Ninety-five percent (246 of 259) of the control households stored at least one pesticide product (median, 4). Indicators of higher sociodemographic status predicted more products in storage. We identified the most common characteristics: storage areas (garage, 40%; kitchen, 20%), pests treated (ants, 33%; weeds, 20%), pesticide types (insecticides, 46%; herbicides, 24%), chemical classes (pyrethroids, 77%; botanicals, 50%), active ingredients (pyrethrins, 43%) and synergists (piperonyl butoxide, 42%). Products could contain multiple active ingredients.
CONCLUSIONS: Our data on specific active ingredients and patterns of storage and use will inform future etiologic analyses of residential pesticide exposures from self-reported data, particularly among households with young children.
C1 [Guha, Neela; Gunier, Robert; Buffler, Patricia A.; Metayer, Catherine] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
[Guha, Neela] Int Agcy Res Canc, F-69372 Lyon, France.
[Ward, Mary H.; Colt, Joanne S.] NCI, Bethesda, MD 20892 USA.
[Lea, C. Suzanne] E Carolina Univ, Brody Sch Med, Dept Publ Hlth, Greenville, NC USA.
RP Metayer, C (reprint author), 1995 Univ Ave,Suite 460, Berkeley, CA 94704 USA.
EM cmetayer@berkeley.edu
OI Guha, Neela/0000-0003-3991-4662; Gunier, Robert/0000-0001-5485-9919
FU National Institute of Environmental Health Sciences (NIEHS)
[R01ES009137, P42ES04705]; National Cancer Institute (NCI), National
Institutes of Health (NIH) [7590-S-04, 7590-S-01, N02-CP-11015]
FX This work was supported by the National Institute of Environmental
Health Sciences (NIEHS; grants R01ES009137 and P42ES04705), and
partially funded by the Intramural Research Program of the National
Cancer Institute (NCI), National Institutes of Health (NIH; subcontracts
7590-S-04 and 7590-S-01, and contract N02-CP-11015).
NR 37
TC 7
Z9 9
U1 2
U2 32
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 FEB
PY 2013
VL 121
IS 2
BP 276
EP 282
DI 10.1289/ehp.1204926
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 208SX
UT WOS:000323700900033
PM 23110983
ER
PT J
AU Birnbaum, LS
AF Birnbaum, Linda S.
TI 15 Years Out: Reinventing ICCVAM
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
C1 [Birnbaum, Linda S.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Birnbaum, Linda S.] NIH, NTP, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
RP Birnbaum, LS (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM birnbaumls@niehs.nih.gov
NR 2
TC 8
Z9 8
U1 0
U2 0
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 FEB
PY 2013
VL 121
IS 2
BP A40
EP A40
DI 10.1289/ehp.1206292
PG 1
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 208SX
UT WOS:000323700900001
PM 23380598
ER
PT J
AU Moni, M
Rajda, J
Lakshmanadoss, U
AF Moni, Monika
Rajda, Jay
Lakshmanadoss, Umashankar
TI Artefactual spikes in electrocardiography: a worthwhile introspection
SO SINGAPORE MEDICAL JOURNAL
LA English
DT Article
DE artifacts; electrocardiography; implanted neurostimulator
AB Electrical devices, which have become an integral part of our daily life, may influence the electrical recording of the heart. These disturbances from external sources outside of the heart's own activity produce changes in the electrocardiography (ECG) of the patient, simulating rhythmic disturbances of the heart. Understanding these disturbances is essential in order to better interprete the ECG. Common sources of electrical interferences include external devices, such as alternating current and improper earthing, and surgical procedures like diathermy. We report a case of electrical interference in a patient's ECG due to an inserted bladder stimulator. This case report highlights the importance of precise identification of artefacts in the interpretation of ECG, as well as prompt localisation and elimination of the source of interference.
C1 [Moni, Monika] NIA, Clin Res Branch, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Rajda, Jay] Unity Hlth Syst, Dept Internal Med, New York, NY USA.
[Lakshmanadoss, Umashankar] Guthrie Clin, Div Cardiovasc Med, Sayre, PA USA.
RP Lakshmanadoss, U (reprint author), Guthrie Clin, Div Cardiovasc Med, 1 Guthrie Sq, Sayre, PA USA.
EM drlumashankar@gmail.com
NR 6
TC 0
Z9 0
U1 0
U2 2
PU SINGAPORE MEDICAL ASSOC
PI SINGAPORE
PA LEVEL 2 ALUMNI MEDICAL CENTRE, 2 COLLEGE RD, SINGAPORE 169850, SINGAPORE
SN 0037-5675
J9 SINGAP MED J
JI Singap. Med. J.
PD FEB
PY 2013
VL 54
IS 2
BP E46
EP E49
DI 10.11622/smedj.2013040
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 203TM
UT WOS:000323316400007
PM 23462843
ER
PT J
AU Gliwa, C
Berkman, BE
AF Gliwa, Catherine
Berkman, Benjamin E.
TI Do Researchers Have an Obligation to Actively Look for Genetic
Incidental Findings?
SO AMERICAN JOURNAL OF BIOETHICS
LA English
DT Article
DE genetics (clinical); genetic research; human subjects research; research
ethics
ID ANCILLARY-CARE RESPONSIBILITIES; RESEARCH PARTICIPANTS; MEDICAL
RESEARCHERS; ETHICAL FRAMEWORK; CLINICAL-PRACTICE; GENOMIC RESEARCH;
WORKING GROUP; RECOMMENDATIONS; CHALLENGES; VARIANTS
AB The rapid growth of next-generation genetic sequencing has prompted debate about the responsibilities of researchers toward genetic incidental findings. Assuming there is a duty to disclose significant incidental findings, might there be an obligation for researchers to actively look for these findings? We present an ethical framework for analyzing whether there is a positive duty to look for genetic incidental findings. Using the ancillary care framework as a guide, we identify three main criteria that must be present to give rise to an obligation to look: high benefit to participants, lack of alternative access for participants, and reasonable burden on researchers. Our analysis indicates that there is no obligation to look for incidental findings today, but during the ongoing translation of genomic analysis from research to clinical care, this obligation may arise.
C1 [Gliwa, Catherine; Berkman, Benjamin E.] NIH, Bethesda, MD 20892 USA.
[Berkman, Benjamin E.] NHGRI, Bethesda, MD USA.
RP Berkman, BE (reprint author), NIH, Bldg 10 Room 1C118,10 Ctr Dr,MSC 1156, Bethesda, MD 20892 USA.
EM berkmanbe@mail.nih.gov
FU Intramural Research Program of NHGRI, NIH
FX The authors would like to thank Ben Solomon, Sara Hull, Karen
Rothenberg, Justin Lowenthal, and all of our colleagues in the NIH
Department of Bioethics for their thoughtful advice and careful reviews
throughout this project. The opinions expressed in this article are
those of the authors. No statement in this article should be construed
as an official position of the National Human Genome Research Institute,
National Institutes of Health, or Department of Health and Human
Services. This research was supported by the Intramural Research Program
of NHGRI, NIH.
NR 42
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U1 4
U2 16
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1526-5161
J9 AM J BIOETHICS
JI Am. J. Bioeth.
PD FEB 1
PY 2013
VL 13
IS 2
BP 32
EP 42
DI 10.1080/15265161.2012.754062
PG 11
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 189YG
UT WOS:000322303600013
PM 23391059
ER
PT J
AU Biesecker, LG
AF Biesecker, Leslie G.
TI The Nirvana Fallacy and the Return of Results
SO AMERICAN JOURNAL OF BIOETHICS
LA English
DT Editorial Material
C1 [Biesecker, Leslie G.] NHGRI, Bethesda, MD USA.
RP Biesecker, LG (reprint author), 49 Convent Dr,Room 4A56, Bethesda, MD 20892 USA.
EM lesb@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute of the National Institutes of Health
FX This commentary represents the individual views of the author and does
not necessarily represent the views of the institutions to which the
author is affiliated. The author is supported by the Intramural Research
Program of the National Human Genome Research Institute of the National
Institutes of Health.
NR 3
TC 6
Z9 6
U1 0
U2 2
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1526-5161
EI 1536-0075
J9 AM J BIOETHICS
JI Am. J. Bioeth.
PD FEB 1
PY 2013
VL 13
IS 2
BP 43
EP 44
DI 10.1080/15265161.2013.755826
PG 2
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 189YG
UT WOS:000322303600014
PM 23391060
ER
PT J
AU Karamzadeh, N
Medvedev, A
Azari, A
Gandjbakhche, A
Najafizadeh, L
AF Karamzadeh, Nader
Medvedev, Andrei
Azari, Afrouz
Gandjbakhche, Amir
Najafizadeh, Laleh
TI Capturing dynamic patterns of task-based functional connectivity with
EEG
SO NEUROIMAGE
LA English
DT Article
DE Electroencephalography (EEG); Functional connectivity; Clustering
analysis
ID EVENT-RELATED POTENTIALS; QUANTIFYING STATISTICAL INTERDEPENDENCE;
INDEPENDENT COMPONENT ANALYSIS; ODDBALL TASK; ALZHEIMERS-DISEASE;
POINT-PROCESSES; WORKING-MEMORY; VISUAL P300; SCHIZOPHRENIA; NETWORKS
AB A new approach to trace the dynamic patterns of task-based functional connectivity, by combining signal segmentation, dynamic time warping (DTW), and Quality Threshold (QT) clustering techniques, is presented. Electroencephalography (EEG) signals of 5 healthy subjects were recorded as they performed an auditory oddball and a visual modified oddball tasks. To capture the dynamic patterns of functional connectivity during the execution of each task, EEG signals are segmented into durations that correspond to the temporal windows of previously well-studied event-related potentials (ERPs). For each temporal window, DTW is employed to measure the functional similarities among channels. Unlike commonly used temporal similarity measures, such as cross correlation, DTW compares time series by taking into consideration that their alignment properties may vary in time. QT clustering analysis is then used to automatically identify the functionally connected regions in each temporal window. For each task, the proposed approach was able to establish a unique sequence of dynamic pattern (observed in all 5 subjects) for brain functional connectivity. Published by Elsevier Inc.
C1 [Karamzadeh, Nader; Azari, Afrouz; Gandjbakhche, Amir; Najafizadeh, Laleh] NICHHD, Natl Inst Hlth, SAFB, Bethesda, MD 20892 USA.
[Karamzadeh, Nader] George Mason Univ, Sch Phys Astron & Computat Sci, Fairfax, VA 22030 USA.
[Medvedev, Andrei] Georgetown Univ, Ctr Funct & Mol Imaging, Washington, DC USA.
[Azari, Afrouz] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA.
[Najafizadeh, Laleh] Rutgers State Univ, Dept Elect & Comp Engn, Piscataway, NJ 08855 USA.
[Karamzadeh, Nader; Najafizadeh, Laleh] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
RP Gandjbakhche, A (reprint author), NICHHD, Natl Inst Hlth, SAFB, Bethesda, MD 20892 USA.
EM amir@helix.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; Department of Defense in the Center for Neuroscience and
Regenerative Medicine
FX We acknowledge the funding of the intramural program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development. Also support for this work included funding from Department
of Defense in the Center for Neuroscience and Regenerative Medicine.
NR 58
TC 10
Z9 10
U1 1
U2 12
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 FEB 1
PY 2013
VL 66
BP 311
EP 317
DI 10.1016/j.neuroimage.2012.10.032
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 190QR
UT WOS:000322355800034
PM 23142654
ER
PT J
AU Cho, YST
Fromm, S
Guyer, AE
Detloff, A
Pine, DS
Fudge, JL
Ernst, M
AF Cho, Youngsun T.
Fromm, Stephen
Guyer, Amanda E.
Detloff, Allison
Pine, Daniel S.
Fudge, Julie L.
Ernst, Monique
TI Nucleus accumbens, thalamus and insula connectivity during incentive
anticipation in typical adults and adolescents
SO NEUROIMAGE
LA English
DT Article
ID WHITE-MATTER DEVELOPMENT; RISKY DECISION-MAKING; PREFRONTAL CORTEX;
NEURAL RESPONSES; RHESUS-MONKEY; BASAL GANGLIA; PARAVENTRICULAR NUCLEUS;
PHYSIOLOGICAL CONDITION; REWARD ANTICIPATION; NEURONAL-ACTIVITY
AB Reward neurocircuitry links motivation with complex behavioral responses. Studies of incentive processing have repeatedly demonstrated activation of nucleus accumbens (NAc), thalamus, and anterior insula, three key components of reward neurocircuitry. The contribution of the thalamus to this circuitry in humans has been relatively ignored, a gap that needs to be filled, given the central role of this structure in processing and filtering information. This study aimed to understand how these three regions function as a network during gain or loss anticipation in adults and youth. Towards this goal, functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) were used to examine effective connectivity among these three nodes in healthy adults and adolescents who performed the monetary incentive delay (MID) task. Seven connectivity models, based on anatomic connections, were tested. They were estimated for incentive anticipation and underwent Bayesian Model Selection (BMS) to determine the best-fit model for each adult and adolescent group. Connection strengths were extracted from the best-fit model and examined for significance in each group. These variables were then entered into a linear mixed model to test between-group effects on effective connectivity in reward neurocircuitry. The best-fit model for both groups included all possible anatomic connections. Three main findings emerged: (1) Across the task, thalamus and insula significantly influenced NAc; (2) A broader set of significant connections was found for the loss-cue condition than the gain-cue condition in both groups; (3) Finally, between-group comparisons of connectivity strength failed to detect statistical differences, suggesting that adults and adolescents use this incentive-processing network in a similar manner. This study demonstrates the way in which the thalamus and insula influence the NAc during incentive processing in humans. Specifically, this is the first study to demonstrate in humans the key role of thalamus projections onto the NAc in support of reward processing. Our results suggest that anticipation of gain/loss involves an 'alerting' signal (thalamus) that converges with interoceptive information (insula) to shape action selection programs in the ventral striatum. Published by Elsevier Inc.
C1 [Cho, Youngsun T.; Fudge, Julie L.] Univ Rochester, Med Ctr, Dept Neurobiol & Anat, Rochester, NY 14627 USA.
[Fromm, Stephen; Detloff, Allison; Pine, Daniel S.; Ernst, Monique] NIMH, NIH, DHHS, Sect Dev & Affect Neurosci Branch, Bethesda, MD 20892 USA.
[Guyer, Amanda E.] Univ Calif Davis, Ctr Mind & Brain, Davis, CA 95616 USA.
RP Ernst, M (reprint author), NIMH, Natl Inst Hlth, Emot Dev & Affect Neurosci Branch EDAN, 15K North Dr, Bethesda, MD 20892 USA.
EM ernstm@mail.nih.gov
FU Intramural Research Program-NIMH [F30 MH091926-02]
FX F30 MH091926-02 (YTC); Intramural Research Program-NIMH.
NR 98
TC 27
Z9 27
U1 6
U2 22
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 FEB 1
PY 2013
VL 66
BP 508
EP 521
DI 10.1016/j.neuroimage.2012.10.013
PG 14
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 190QR
UT WOS:000322355800053
PM 23069809
ER
PT J
AU Sutherland, MT
Carroll, AJ
Salmeron, BJ
Ross, TJ
Hong, LE
Stein, EA
AF Sutherland, Matthew T.
Carroll, Allison J.
Salmeron, Betty Jo
Ross, Thomas J.
Hong, L. Elliot
Stein, Elliot A.
TI Individual differences in amygdala reactivity following nicotinic
receptor stimulation in abstinent smokers
SO NEUROIMAGE
LA English
DT Article
DE Varenicline; Nicotine; Withdrawal; Amygdala; Emotion; Functional
magnetic resonance imaging (fMRI)
ID SUSTAINED-RELEASE BUPROPION; RANDOMIZED CONTROLLED-TRIAL;
SMOKING-CESSATION; PARTIAL AGONIST; COGNITIVE PERFORMANCE; BRAIN
ACTIVITY; QUANTITATIVE METAANALYSIS; TRANSDERMAL NICOTINE; TOBACCO
WITHDRAWAL; VARENICLINE
AB Hyperactive amygdala functioning may. underlie emotional dysregulation during smoking abstinence and represents one neurobiological target for pharmacological cessation aids. Available pharmacotherapies (e.g., nicotine replacement and varenicline) aid only a subset of individuals with smoking cessation and therefore elucidating the neurobiological impact of these medications is critical to expedite improved interventions. In a fMRI study employing a within-subject, double-blind, placebo-controlled design, we assessed task performance and amygdala functioning during an emotional face matching paradigm following administration of nicotine and varenicline to 24 abstinent smokers and 20 nonsmokers. All participants underwent similar to 17 days of varenicline and placebo pill administration and were scanned, on different days under each condition, wearing a transdermal nicotine or placebo patch. During the amygdala reactivity paradigm, nicotinic acetylcholine receptor (nAChR) stimulation by nicotine and varenicline decreased reaction time (RT) in abstinent smokers but not in nonsmokers. When considering all smokers as a single homogenous group, no drug-induced effects on amygdala reactivity were detected. However, in an exploratory analysis we parsed participants into subgroups according to individual differences in the propensity to demonstrate stable performance augmentation following nAChR stimulation (stable RT-improvers [SI] vs. variable RT-improvers [VI]). Using this exploratory approach, drugs appeared to modulate amygdala reactivity in only one smoker subgroup but not in either nonsmoker subgroup. Specifically, in the SI-smoker cohort abstinence-induced elevated amygdala reactivity was down-regulated by nAChR stimulation. In contrast, varenicline and nicotine did not modulate amygdala functioning in the VI-smoker cohort who displayed moderate levels of amygdala reactivity in the absence of drug administration. These results suggest that pharmacotherapies most robustly dampened amygdala functioning in smokers appearing susceptible to abstinence-induced effects. Such findings provide a step towards fractionating the smoker phenotype by discrete neurobiological characteristics. Published by Elsevier Inc.
C1 [Sutherland, Matthew T.; Carroll, Allison J.; Salmeron, Betty Jo; Ross, Thomas J.; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH DHHS, Baltimore, MD USA.
[Hong, L. Elliot] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA.
RP Sutherland, MT (reprint author), Florida Int Univ, Dept Psychol, Miami, FL 33199 USA.
EM masuther@fiu.edu
RI Salmeron, Betty Jo/M-1793-2016;
OI Salmeron, Betty Jo/0000-0003-1699-9333; Ross, Thomas/0000-0002-7745-3572
FU National Institute on Drug Abuse, Intramural Research Program, National
Institutes of Health, Department of Health and Human Services
(NIDA-IRP/NIH/DHHS)
FX This work was sponsored by the National Institute on Drug Abuse,
Intramural Research Program, National Institutes of Health, Department
of Health and Human Services (NIDA-IRP/NIH/DHHS). We thank Eliscia
Smith, Angela Neal, Kimberly Slater, Loretta Spurgeon, and the NIDA-IRP
nurses, pharmacy, and recruitment staff for their assistance with data
collection.
NR 57
TC 3
Z9 3
U1 1
U2 6
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 FEB 1
PY 2013
VL 66
BP 585
EP 593
DI 10.1016/j.neuroimage.2012.10.043
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 190QR
UT WOS:000322355800060
PM 23110878
ER
PT J
AU Misaki, M
Luh, WM
Bandettini, PA
AF Misaki, Masaya
Luh, Wen-Ming
Bandettini, Peter A.
TI Accurate decoding of sub-TR timing differences in stimulations of
sub-voxel regions from multi-voxel response patterns
SO NEUROIMAGE
LA English
DT Article
DE Multi-voxel pattern analysis; Deconvolved hemodynamic response;
Hyper-spatiotemporal resolution; Complex spatiotemporal filter voxel
ID PRIMARY VISUAL-CORTEX; INFERIOR TEMPORAL CORTEX; EVENT-RELATED FMRI;
IMPULSE-RESPONSE; FUNCTIONAL MRI; BOLD RESPONSES; NEGATIVE BOLD;
INFORMATION; TIME; CLASSIFICATION
AB We investigated the decoding of ocular dominance stimulations with millisecond-order timing difference from the blood oxygen level dependent (BOLD) signal in human functional magnetic resonance imaging (fMRI). In our experiment, ocular dominance columns were activated by monocular visual stimulation with 500- or 100- ms onset differences. We observed that the event-related hemodynamic response (HDR) in the human visual cortex was sensitive to the subtle onset difference. The HDR shapes were related to the stimulus timings in various manners: the timing difference was represented in either the amplitude of positive peak, amplitude of negative peak, delay of peak time, or response duration of HDR. These complex relationships were different across voxels and subjects. To find an informative feature of HDR for discriminating the subtle timing difference of ocular dominance stimulations, we examined various characteristics of HDR including response amplitude, time to peak, full width at half-maximum response, as inputs for decoding analysis. Using a canonical HDR function for estimating the voxel's response did not yield good decoding scores, suggesting that information may reside in the variability of HDR shapes. Using all the values from the deconvolved HDR also showed low performance, which could be due to an over-fitting problem with the large data dimensionality. When using either positive or negative peak amplitude of the deconvolved HDR, high decoding performance could be achieved for both the 500 ms and the 100 ms onset differences. The high accuracy even for the 100 ms difference, given that the signal was sampled at a TR of 250 ms and 2 x 2 x 3-mm voxels, implies a possibility of spatiotemporally hyper-resolution decoding. Furthermore, both down-sampling and smoothing did not affect the decoding accuracies very much. These results suggest a complex spatiotemporal relationship between the multi-voxel pattern of the BOLD response and the population activation of neuronal columns. The demonstrated possibility of decoding stimulations for columnar-level organization with 100-ms onset difference using lower resolution imaging data may broaden the scope of application of the BOLD fMRI. Published by Elsevier Inc.
C1 [Misaki, Masaya; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Luh, Wen-Ming; Bandettini, Peter A.] NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA.
RP Misaki, M (reprint author), Laureate Inst Brain Res, 6655 S Yale Ave, Tulsa, OK 74136 USA.
EM mmisaki@laureateinstitute.org
FU National Institutes of Health, National Institute of Mental Health
(NIMH)
FX This study was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Mental Health
(NIMH). This study utilized the high performance computational
capabilities of the Biowulf Linux cluster at the National Institutes of
Health, Bethesda, MD (http://biowulf.nih.gov).
NR 52
TC 2
Z9 2
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD FEB 1
PY 2013
VL 66
BP 623
EP 633
DI 10.1016/j.neuroimage.2012.10.069
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 190QR
UT WOS:000322355800064
PM 23128073
ER
PT J
AU Blagoev, KB
Wilkerson, J
Stein, WD
Motzer, RJ
Bates, SE
Fojo, AT
AF Blagoev, Krastan B.
Wilkerson, Julia
Stein, Wilfred D.
Motzer, Robert J.
Bates, Susan E.
Fojo, A. Tito
TI Sunitinib Does Not Accelerate Tumor Growth in Patients with Metastatic
Renal Cell Carcinoma
SO CELL REPORTS
LA English
DT Article
ID INTERFERON-ALPHA; ANGIOGENESIS; INHIBITOR; SURVIVAL; CANCER
AB Preclinical studies have suggested that sunitinib accelerates metastases in animals, ascribing this to inhibition of the vascular endothelial growth factor receptor or the tumor's adaptation. To address whether sunitinib accelerates tumors in humans, we analyzed data from the pivotal randomized phase III trial comparing sunitinib and interferon alfa in patients with metastatic renal cell carcinoma. The evidence clearly shows that sunitinib was not harmful, did not accelerate tumor growth, and did not shorten survival. Specifically, neither longer sunitinib treatment nor a greater effect of sunitinib on tumors reduced survival. Sunitinib did reduce the tumor's growth rate while administered, thereby improving survival, without appearing to alter tumor biology after discontinuation. Concerns arising from animal models do not apply to patients receiving sunitinib and likely will not apply to similar agents.
C1 [Blagoev, Krastan B.] Natl Sci Fdn, Arlington, VA 22030 USA.
[Wilkerson, Julia; Stein, Wilfred D.; Bates, Susan E.; Fojo, A. Tito] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Stein, Wilfred D.] Hebrew Univ Jerusalem, Jerusalem, Israel.
[Motzer, Robert J.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
RP Blagoev, KB (reprint author), Natl Sci Fdn, Arlington, VA 22030 USA.
EM kblagoev@nsf.gov; fojot@mail.nih.gov
OI Wilkerson, Julia/0000-0002-6965-0867
FU National Science Foundation
FX K.B.B. was supported by the National Science Foundation, while working
at the Foundation. Any opinion, finding, and conclusions or
recommendations expressed in this material are those of the authors and
do not necessarily reflect the views of the National Science Foundation.
NR 15
TC 23
Z9 25
U1 0
U2 5
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 FEB
PY 2013
VL 3
IS 2
BP 277
EP 281
DI 10.1016/j.celrep.2013.01.015
PG 5
WC Cell Biology
SC Cell Biology
GA 184MS
UT WOS:000321895200002
PM 23395639
ER
PT J
AU Zanivan, S
Meves, A
Behrendt, K
Schoof, EM
Neilson, LJ
Cox, J
Tang, HR
Kalna, G
van Ree, JH
van Deursen, JM
Trempus, CS
Machesky, LM
Linding, R
Wickstrom, SA
Fassler, R
Mann, M
AF Zanivan, Sara
Meves, Alexander
Behrendt, Kristina
Schoof, Erwin M.
Neilson, Lisa J.
Cox, Juergen
Tang, Hao R.
Kalna, Gabriela
van Ree, Janine H.
van Deursen, Jan M.
Trempus, Carol S.
Machesky, Laura M.
Linding, Rune
Wickstroem, Sara A.
Faessler, Reinhard
Mann, Matthias
TI In Vivo SILAC-Based Proteomics Reveals Phosphoproteome Changes during
Mouse Skin Carcinogenesis
SO CELL REPORTS
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; RESOLUTION MASS-SPECTROMETRY; GENE-EXPRESSION;
QUANTITATIVE PROTEOMICS; FEEDBACK PHOSPHORYLATION; RETINOBLASTOMA
PROTEIN; RETINOIC ACID; AMINO-ACIDS; CANCER; PROGRESSION
AB Cancer progresses through distinct stages, and mouse models recapitulating traits of this progression are frequently used to explore genetic, morphological, and pharmacological aspects of tumor development. To complement genomic investigations of this process, we here quantify phosphoproteomic changes in skin cancer development using the SILAC mouse technology coupled to high-resolution mass spectrometry. We distill protein expression signatures from our data that distinguish between skin cancer stages. A distinct phosphoproteome of the two stages of cancer progression is identified that correlates with perturbed cell growth and implicates cell adhesion as a major driver of malignancy. Importantly, integrated analysis of phosphoproteomic data and prediction of kinase activity revealed PAK4-PKC/SRC network to be highly deregulated in SCC but not in papilloma. This detailed molecular picture, both at the proteome and phosphoproteome level, will prove useful for the study of mechanisms of tumor progression.
C1 [Zanivan, Sara; Cox, Juergen; Mann, Matthias] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany.
[Meves, Alexander; Faessler, Reinhard] Max Planck Inst Biochem, Dept Mol Med, D-82152 Martinsried, Germany.
[Zanivan, Sara; Neilson, Lisa J.; Tang, Hao R.; Kalna, Gabriela; Machesky, Laura M.] Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland.
[Meves, Alexander] Mayo Clin, Coll Med, Dept Dermatol, Rochester, MN 55905 USA.
[van Ree, Janine H.; van Deursen, Jan M.] Mayo Clin, Coll Med, Dept Pediat & Adolescent Med, Rochester, MN 55905 USA.
[Behrendt, Kristina; Wickstroem, Sara A.] Max Planck Inst Biol Ageing, Paul Gerson Unna Grp Skin Homeostasis & Ageing, D-50931 Cologne, Germany.
[Schoof, Erwin M.; Linding, Rune] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal CBS, Cellular Signal Integrat Grp, DK-2800 Lyngby, Denmark.
[Trempus, Carol S.] NIEHS, Matrix Biol Grp, Lab Resp Biol, Res Triangle Pk, NC 27709 USA.
[Mann, Matthias] Univ Copenhagen, Fac Hlth Sci, Novo Nordisk Fdn Ctr Prot Res, DK-2200 Copenhagen, Denmark.
RP Zanivan, S (reprint author), Max Planck Inst Biochem, Dept Prote & Signal Transduct, Klopferspitz 18, D-82152 Martinsried, Germany.
EM s.zanivan@beatson.gla.ac.uk; mmann@biochem.mpg.de
RI Mann, Matthias/A-3454-2013; Cox, Jurgen/B-9481-2008
OI Mann, Matthias/0000-0003-1292-4799; Cox, Jurgen/0000-0001-8597-205X
FU Max-Planck Society; EC-FP7 (Metafight); PROSPECT, a 7th framework
program of the European Union [HEALTH-F4-2008-201648]; Cancer Research
UK; Danish Council for Independent Research; Human Frontier Science
Program; Fondazione Italiana per la Ricerca sul Cancro (FIRC);
Associazione Italiana per la Ricerca sul Cancro
FX We thank Mark Pittelkow for fruitful discussions. This work was
supported by the Max-Planck Society, EC-FP7 (Metafight), PROSPECT, a 7th
framework program of the European Union (grant agreement
HEALTH-F4-2008-201648), and Cancer Research UK. C.S.T.'s work was
conducted in the Intramural Division of the NIEHS. R.L. is a Lundbeck
Foundation Fellow and is supported by a Sapere Aude Starting Grant from
The Danish Council for Independent Research and a Career Development
Award from Human Frontier Science Program. S.Z. was partially supported
by the fellowship "L. Fontana e M. Lionello" granted by Fondazione
Italiana per la Ricerca sul Cancro (FIRC).
NR 62
TC 45
Z9 50
U1 0
U2 35
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 FEB
PY 2013
VL 3
IS 2
BP 552
EP 566
DI 10.1016/j.celrep.2013.01.003
PG 15
WC Cell Biology
SC Cell Biology
GA 184MS
UT WOS:000321895200027
PM 23375375
ER
PT J
AU Ke, RA
Aaskov, J
Holmes, EC
Lloyd-Smith, JO
AF Ke, Ruian
Aaskov, John
Holmes, Edward C.
Lloyd-Smith, James O.
TI Phylodynamic Analysis of the Emergence and Epidemiological Impact of
Transmissible Defective Dengue Viruses
SO PLOS PATHOGENS
LA English
DT Article
ID WEST-NILE-VIRUS; VESICULAR STOMATITIS-VIRUS; COOPERATIVE INTERACTIONS;
RNA VIRUSES; DIVERSITY; MOSQUITOS; DYNAMICS; MICROEVOLUTION;
TRANSCRIPTASE; POPULATION
AB Intra-host sequence data from RNA viruses have revealed the ubiquity of defective viruses in natural viral populations, sometimes at surprisingly high frequency. Although defective viruses have long been known to laboratory virologists, their relevance in clinical and epidemiological settings has not been established. The discovery of long-term transmission of a defective lineage of dengue virus type 1 (DENV-1) in Myanmar, first seen in 2001, raised important questions about the emergence of transmissible defective viruses and their role in viral epidemiology. By combining phylogenetic analyses and dynamical modeling, we investigate how evolutionary and ecological processes at the intra-host and inter-host scales shaped the emergence and spread of the defective DENV-1 lineage. We show that this lineage of defective viruses emerged between June 1998 and February 2001, and that the defective virus was transmitted primarily through co-transmission with the functional virus to uninfected individuals. We provide evidence that, surprisingly, this co-transmission route has a higher transmission potential than transmission of functional dengue viruses alone. Consequently, we predict that the defective lineage should increase overall incidence of dengue infection, which could account for the historically high dengue incidence reported in Myanmar in 2001-2002. Our results show the unappreciated potential for defective viruses to impact the epidemiology of human pathogens, possibly by modifying the virulence-transmissibility trade-off, or to emerge as circulating infections in their own right. They also demonstrate that interactions between viral variants, such as complementation, can open new pathways to viral emergence.
C1 [Ke, Ruian; Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
[Aaskov, John] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia.
[Holmes, Edward C.] Univ Sydney, Sch Biol Sci, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Holmes, Edward C.; Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Ke, RA (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
EM ruian@ucla.edu; jlloydsmith@ucla.edu
RI Lloyd-Smith, James/K-4080-2012;
OI Lloyd-Smith, James/0000-0001-7941-502X; Holmes,
Edward/0000-0001-9596-3552
FU National Science Foundation [EF-0928690]; De Logi Chair in Biological
Sciences; RAPIDD program of the Science & Technology Directorate,
Department of Homeland Security; Fogarty International Center, National
Institutes of Health; National Health and Medical Research Council of
Australia; ECH by the National Institutes of Health [5R01GM087405-03,
R01GM080533-06]
FX JOLS and RK are supported by National Science Foundation (EF-0928690).
JOLS is grateful for support from the De Logi Chair in Biological
Sciences, and from the RAPIDD program of the Science & Technology
Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health. JA is supported by
the National Health and Medical Research Council of Australia, and ECH
by the National Institutes of Health (5R01GM087405-03 and
R01GM080533-06). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 55
TC 13
Z9 13
U1 2
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD FEB
PY 2013
VL 9
IS 2
AR e1003193
DI 10.1371/journal.ppat.1003193
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 184CE
UT WOS:000321863200013
PM 23468631
ER
PT J
AU Mendoza, D
Migueles, SA
Rood, JE
Peterson, B
Johnson, S
Doria-Rose, N
Schneider, D
Rakasz, E
Trivett, MT
Trubey, CM
Coalter, V
Hallahan, CW
Watkins, D
Franchini, G
Lifson, JD
Connors, M
AF Mendoza, Daniel
Migueles, Stephen A.
Rood, Julia E.
Peterson, Bennett
Johnson, Sarah
Doria-Rose, Nicole
Schneider, Douglas
Rakasz, Eva
Trivett, Matthew T.
Trubey, Charles M.
Coalter, Vicky
Hallahan, Claire W.
Watkins, David
Franchini, Genoveffa
Lifson, Jeffrey D.
Connors, Mark
TI Cytotoxic Capacity of SIV-Specific CD8(+) T Cells against Primary
Autologous Targets Correlates with Immune Control in SIV-Infected Rhesus
Macaques
SO PLOS PATHOGENS
LA English
DT Article
ID HIV-INFECTION; VIRUS-REPLICATION; ELITE CONTROLLER; ACTIVATION;
NONPROGRESSORS; HETEROGENEITY; TRANSDUCTION; INDIVIDUALS; LYMPHOCYTES;
INHIBITION
AB Although the study of non-human primates has resulted in important advances for understanding HIV-specific immunity, a clear correlate of immune control over simian immunodeficiency virus (SIV) replication has not been found to date. In this study, CD8(+) T-cell cytotoxic capacity was examined to determine whether this function is a correlate of immune control in the rhesus macaque (RM) SIV infection model as has been suggested in chronic HIV infection. SIVmac251-infected human reverse transcriptase (hTERT)-transduced CD4(+) T-cell clone targets were co-incubated with autologous macaque effector cells to measure infected CD4(+) T-cell elimination (ICE). Twenty-three SIV-infected rhesus macaques with widely varying plasma viral RNA levels were evaluated in a blinded fashion. Nineteen of 23 subjects (83%) were correctly classified as long-term nonprogressor/elite controller (LTNP/EC), slow progressor, progressor or SIV-negative rhesus macaques based on measurements of ICE (weighted Kappa 0.75). LTNP/EC had higher median ICE than progressors (67.3% [22.0-91.7%] vs. 23.7% [0.0-58.0%], p = 0.002). In addition, significant correlations between ICE and viral load (r = 20.57, p = 0.01), and between granzyme B delivery and ICE (r = 0.89, p < 0.001) were observed. Fur