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. Furthermore, the CD8(+) T cells of LTNP/EC exhibited higher per-cell cytotoxic capacity than those of progressors (p = 0.004). These findings support that greater lytic granule loading of virus-specific CD8(+) T cells and efficient delivery of active granzyme B to SIV-infected targets are associated with superior control of SIV infection in rhesus macaques, consistent with observations of HIV infection in humans. Therefore, such measurements appear to represent a correlate of control of viral replication in chronic SIV infection and their role as predictors of immunologic control in the vaccine setting should be evaluated.
C1 [Mendoza, Daniel; Migueles, Stephen A.; Rood, Julia E.; Peterson, Bennett; Johnson, Sarah; Doria-Rose, Nicole; Connors, Mark] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Schneider, Douglas; Trivett, Matthew T.; Trubey, Charles M.; Coalter, Vicky; Lifson, Jeffrey D.] Frederick Natl Lab Canc Res, SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick, MD USA.
[Rakasz, Eva; Watkins, David] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA.
[Hallahan, Claire W.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Watkins, David] Univ Miami, Miller Sch Med, Dept Pathol Clin Res Bldg, Miami, FL 33136 USA.
[Franchini, Genoveffa] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
RP Connors, M (reprint author), NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mconnors@nih.gov
OI Mendoza, Daniel/0000-0002-6362-0771
FU NIAID; National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in part with federal funds from the
Intramural Research Programs of NIAID and the National Cancer Institute,
National Institutes of Health, under Contract No. HHSN261200800001E. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 40
TC 13
Z9 13
U1 0
U2 1
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 e1003195
DI 10.1371/journal.ppat.1003195
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 184CE
UT WOS:000321863200014
PM 23468632
ER
PT J
AU Magnani, JW
Wang, N
Nelson, KP
Connelly, S
Deo, R
Rodondi, N
Schelbert, EB
Garcia, ME
Phillips, CL
Shlipak, MG
Harris, TB
Ellinor, PT
Benjamin, EJ
AF Magnani, Jared W.
Wang, Na
Nelson, Kerrie P.
Connelly, Stephanie
Deo, Rajat
Rodondi, Nicolas
Schelbert, Erik B.
Garcia, Melissa E.
Phillips, Caroline L.
Shlipak, Michael G.
Harris, Tamara B.
Ellinor, Patrick T.
Benjamin, Emelia J.
CA Hlth Aging Body Composition Study
TI Electrocardiographic PR Interval and Adverse Outcomes in Older Adults
The Health, Aging, and Body Composition Study
SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
LA English
DT Article
DE atrial fibrillation; ECG; epidemiology; heart failure; risk factors
ID CONGESTIVE-HEART-FAILURE; MIDDLE-AGED MEN; ATRIAL-FIBRILLATION;
METABOLIC SYNDROME; ATHEROSCLEROSIS RISK; ATRIOVENTRICULAR-BLOCK;
CARDIOVASCULAR-DISEASE; COMMUNITIES; OBESITY; SCORE
AB Background- The electrocardiographic PR interval increases with aging, differs by race, and is associated with atrial fibrillation (AF), pacemaker implantation, and all-cause mortality. We sought to determine the associations between PR interval and heart failure, AF, and mortality in a biracial cohort of older adults.
Methods and Results- The Health, Aging, and Body Composition (Health ABC) Study is a prospective, biracial cohort. We used multivariable Cox proportional hazards models to examine PR interval (hazard ratios expressed per SD increase) and 10-year risks of heart failure, AF, and all-cause mortality. Multivariable models included demographic, anthropometric, and clinical variables in addition to established cardiovascular risk factors. We examined 2722 Health ABC participants (aged 74 +/- 3 years, 51.9% women, and 41% black). We did not identify significant effect modification by race for the outcomes studied. After multivariable adjustment, every SD increase (29 ms) in PR interval was associated with a 13% greater 10-year risk of heart failure (95% confidence interval, 1.02-1.25) and a 13% increased risk of incident AF (95% confidence interval, 1.04-1.23). PR interval >200 ms was associated with a 46% increased risk of incident heart failure (95% confidence interval, 1.11-1.93). PR interval was not associated with increased all-cause mortality.
Conclusions- We identified significant relationships of PR interval to heart failure and AF in older adults. Our findings extend prior investigations by examining PR interval and associations with adverse outcomes in a biracial cohort of older men and women.
C1 [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Dept Med, Cardiol Sect,Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Magnani, Jared W.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA 02118 USA.
[Wang, Na] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02118 USA.
[Nelson, Kerrie P.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
[Connelly, Stephanie] Univ Tennessee, Dept Med, Memphis, TN 38104 USA.
[Deo, Rajat] Univ Penn, Div Cardiovasc Med, Sect Electrophysiol, Philadelphia, PA 19104 USA.
[Rodondi, Nicolas] Univ Bern, Dept Gen Internal Med, Bern, Switzerland.
[Schelbert, Erik B.] Univ Pittsburgh, Cardiovasc Inst, Pittsburgh, PA USA.
[Garcia, Melissa E.; Phillips, Caroline L.; Harris, Tamara B.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94143 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown & Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
RP Magnani, JW (reprint author), Boston Univ, Sch Med, 88 E Newton St, Boston, MA 02118 USA.
EM jmagnani@bu.edu
OI Benjamin, Emelia/0000-0003-4076-2336
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging; American Heart Association Award
[09FTF2190028]; National Institute on Aging (NIA) [N01-AG-6-2101,
N01-AG-6-2103, N01-AG-6-2106]; NIA grant [R01-AG028050]; National
Institute of Nursing Research grant [R01-NR012459]; National Institutes
of Health [1RC1HL101056, 1RO1HL092577, 5R21DA027021, 1RO1HL104156,
1K24HL105780, K23DK089118]
FX This research was supported, in part, by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging.; This
research was funded by American Heart Association Award 09FTF2190028
(J.W.M.); by National Institute on Aging (NIA) Contracts N01-AG-6-2101,
N01-AG-6-2103, and N01-AG-6-2106; NIA grant R01-AG028050; National
Institute of Nursing Research grant R01-NR012459, and by National
Institutes of Health grants 1RC1HL101056 (E.J.B.), 1RO1HL092577 (E.J.B.
and P.T.E.), 5R21DA027021, 1RO1HL104156, 1K24HL105780 (P.T.E.), and
K23DK089118 (R.D.).
NR 31
TC 32
Z9 33
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-3149
J9 CIRC-ARRHYTHMIA ELEC
JI Circ.-Arrhythmia Electrophysiol.
PD FEB
PY 2013
VL 6
IS 1
BP 84
EP 90
DI 10.1161/CIRCEP.112.975342
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 167YE
UT WOS:000320670700016
PM 23243193
ER
PT J
AU Sulima, A
Cheng, KJ
Jacobson, AE
Rice, KC
Gawrisch, K
Lee, YS
AF Sulima, Agnieszka
Cheng, Kejun
Jacobson, Arthur E.
Rice, Kenner C.
Gawrisch, Klaus
Lee, Yong-Sok
TI Z and E rotamers of N-formyl-1-bromo-4-hydroxy-3-methoxymorphinan-6-one
and their interconversion as studied by H-1/C-13 NMR spectroscopy and
quantum chemical calculations
SO MAGNETIC RESONANCE IN CHEMISTRY
LA English
DT Article
DE H-1/C-13 NMR; NOE; Z and E rotamers; morphine intermediate; quantum
chemistry; transition state
ID NUCLEAR-MAGNETIC-RESONANCE; HINDERED ROTATION; DERIVATIVES; INVERSION;
SPECTRA; AMIDES; SHIFTS; H-1
AB N-Formyl-1-bromo-4-hydroxy-3-methoxymorphinan-6-one (compound 2), an important intermediate in the NIH Opiate Total Synthesis, presumably exists as a mixture of two rotamers (Z and E) in both CHCl3 and DMSO at room temperature due to the hindered rotation of its N-C18 bond in the amide moiety. By comparing the experimental H-1 and C-13 chemical shifts of a single rotamer and the mixture of compound 2 in CDCl3 with the calculated chemical shifts of the geometry optimized Z and E rotamers utilizing density functional theory, the crystalline rotamer of compound 2 was characterized as having the E configuration. The energy barrier between the two rotamers was also determined with the temperature dependence of H-1 and C-13 NMR coalescence experiments, and then compared with that from the reaction path for the interconversion of the two rotamers calculated at the level of B3LYP/6-31G*. Detailed geometry of the ground state and the transition states of both rotamers are given and discussed. Copyright (c) 2012 This article is a US Government work and is in the public domain in the USA.
C1 [Sulima, Agnieszka; Cheng, Kejun; Jacobson, Arthur E.; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Sulima, Agnieszka; Cheng, Kejun; Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Sulima, Agnieszka] NHLBI, Imaging Probe Dev Ctr, NIH, Bethesda, MD 20892 USA.
[Gawrisch, Klaus] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD USA.
[Lee, Yong-Sok] NIH, Ctr Mol Modeling, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Lee, YS (reprint author), NIH, Ctr Mol Modeling, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
EM leeys@mail.nih.gov
FU NIH Intramural Research Programs of the National Institute on Drug
Abuse; National Institute of Alcohol Abuse and Alcoholism; National
Institute of Diabetes and Digestive and Kidney Diseases; NIH Intramural
Research Program through the Center for Information Technology; NIAAA
FX This work was initiated while the authors (AS, AEJ, and KCR) were
members of the Drug Design and Synthesis Section, Laboratory of
Medicinal Chemistry, National Institute of Diabetes, Digestive and
Kidney Diseases, NIH. The research of the Drug Design and Synthesis
Section, CBRB, NIDA, and NIAAA, was supported by the NIH Intramural
Research Programs of the National Institute on Drug Abuse, the National
Institute of Alcohol Abuse and Alcoholism, and the National Institute of
Diabetes and Digestive and Kidney Diseases. The quantum chemical study
utilized PC/LINUX clusters at the Center for Molecular Modeling of the
NIH (http://cit.nih.gov), and this research was supported by the NIH
Intramural Research Program through the Center for Information
Technology and NIAAA. The authors thank Drs. Umesha Shetty and Victor
Pike, PET Radiopharmaceutical Sciences Molecular Imaging Branch National
Institute of Mental Health, NIH for their help with the high-temperature
NMR experiments (1H and 13C NMR), and Dr. John
Lloyd (Mass Spectrometry Facility, NIDDK, NIH) for the mass spectra.
NR 25
TC 5
Z9 5
U1 0
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0749-1581
J9 MAGN RESON CHEM
JI Magn. Reson. Chem.
PD FEB
PY 2013
VL 51
IS 2
BP 82
EP 88
DI 10.1002/mrc.3909
PG 7
WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy
SC Chemistry; Spectroscopy
GA 158JR
UT WOS:000319966500004
PM 23233124
ER
PT J
AU Chen, JJ
Mikelis, CM
Zhang, YQ
Gutkind, JS
Zhang, BL
AF Chen, Jun-Jie
Mikelis, Constantinos M.
Zhang, Yaqin
Gutkind, J. Silvio
Zhang, Baolin
TI TRAIL induces apoptosis in oral squamous carcinoma cells - a crosstalk
with oncogenic Ras regulated cell surface expression of death receptor 5
SO ONCOTARGET
LA English
DT Article
DE oral cancer; TRAIL; death receptors; apoptosis; Ras; oncotarget
ID CANCER-CELLS; MEDIATED APOPTOSIS; TUMOR-GROWTH; NECK-CANCER; LIGAND;
ACTIVATION; INHIBITION; PATHWAY; HEAD; TRANSFORMATION
AB TNF-related apoptosis inducing ligand (TRAIL) induces apoptosis through its death receptors (DRs) 4 and/or 5 expressed on the surface of target cells. The selectivity of TRAIL towards cancer cells has promoted clinical evaluation of recombinant human TRAIL (rhTRAIL) and its agonistic antibodies in treating several major human cancers including colon and non-Hodgkin's lymphoma. However, little is known about their ability in killing oral squamous cell carcinoma (OSCC) cells. In this study, we tested the apoptotic responses of a panel of seven human OSCC cell lines (HN31, HN30, HN12, HN6, HN4, Cal27, and OSCC3) to rhTRAIL and monoclonal antibodies against DR4 or DR5. We found that rhTRAIL is a potent inducer of apoptosis in most of the oral cancer cell lines tested both in vitro and in vivo. We also showed that DR5 was expressed on the surface of the tested cell lines which correlated with the cellular susceptibility to apoptosis induced by rhTRAIL and anti-DR5 antibody. By contrast, little or no DR4 was detected on the surface of OSCC3 and HN6 cells rendering cellular resistance to DR4 antibody and a reduced sensitivity to rhTRAIL. Notably, the overall TRAIL sensitivity correlated well with the levels of endogenous active Ras in the cell lines tested. Expression of a constitutively active Ras mutant (RasV12) in OSCC3 cells selectively upregulated surface expression of DR5, but not DR4, and restored TRAIL sensitivity. Our findings could have implications for the use of TRAIL receptor targeted therapies in the treatment of human OSCC tumors particularly the ones harboring constitutively active Ras mutant.
C1 [Chen, Jun-Jie; Zhang, Yaqin; Zhang, Baolin] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Off Biotechnol Prod, Bethesda, MD 20014 USA.
[Mikelis, Constantinos M.; Gutkind, J. Silvio] NIH, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA.
RP Zhang, BL (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Off Biotechnol Prod, Bethesda, MD 20014 USA.
EM Baolin.Zhang@fda.hhs.gov
FU U.S. FDA Critical Path Research
FX This project is supported by funding from the U.S. FDA Critical Path
Research.
NR 42
TC 15
Z9 16
U1 0
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD FEB
PY 2013
VL 4
IS 2
BP 206
EP 217
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 142FO
UT WOS:000318782500008
PM 23470485
ER
PT J
AU Tarlykov, PV
Zholdybayeva, EV
Akilzhanova, AR
Nurkina, ZM
Sabitov, ZM
Rahypbekov, TK
Ramanculov, EM
AF Tarlykov, Pavel V.
Zholdybayeva, Elena V.
Akilzhanova, Ainur R.
Nurkina, Zhannur M.
Sabitov, Zhaxylyk M.
Rahypbekov, Tolubay K.
Ramanculov, Erlan M.
TI Mitochondrial and Y-chromosomal profile of the Kazakh population from
East Kazakhstan
SO CROATIAN MEDICAL JOURNAL
LA English
DT Article
ID CENTRAL-ASIAN POPULATIONS; GENETIC-VARIATION; DNA SEQUENCES; SILK ROAD;
DIVERSITY; MTDNA; ANCESTRY; SIBERIA; HISTORY; REGION
AB Aim To study the genetic relationship of Kazakhs from East Kazakhstan to other Eurasian populations by examining paternal and maternal DNA lineages.
Methods Whole blood samples were collected in 2010 from 160 unrelated healthy Kazakhs residing in East Kazakhstan. Genomic DNA was extracted with Wizard genomic DNA Purification Kit. Nucleotide sequence of hypervariable segment I of mitochondrial DNA (mtDNA) was determined and analyzed. Seventeen Y-short tandem repeat (STR) loci were studied in 67 samples with the Amp-FiSTR Y-filer PCR Amplification Kit. In addition, mtDNA data for 2701 individuals and Y-SIR data for 677 individuals were retrieved from the literature for comparison.
Results There was a high degree of genetic differentiation on the level of mitochondrial DNA. The majority of maternal lineages belonged to haplogroups common in Central Asia. In contrast, Y-STR data showed very low genetic diversity, with the relative frequency of the predominant haplotype of 0.612.
Conclusion The results revealed different migration patterns in the population sample, showing there had been more migration among women. mtDNA genetic diversity in this population was equivalent to that in other Central Asian populations. Genetic evidence suggests the existence of a single paternal founder lineage in the population of East Kazakhstan, which is consistent with verbal genealogical data of the local tribes.
C1 [Tarlykov, Pavel V.; Zholdybayeva, Elena V.; Akilzhanova, Ainur R.; Nurkina, Zhannur M.; Ramanculov, Erlan M.] Natl Ctr Biotechnol Republ Kazakhstan, Astana 010000, Kazakhstan.
[Sabitov, Zhaxylyk M.] LN Gumilyov Eurasian Natl Univ, Astana, Kazakhstan.
[Rahypbekov, Tolubay K.] Semey State Med Univ, Semey, Kazakhstan.
RP Tarlykov, PV (reprint author), Natl Ctr Biotechnol Republ Kazakhstan, 13-1 Valikhanov St, Astana 010000, Kazakhstan.
EM pavel.tarlykov@gmail.com
RI Ramanculov, Erlan/E-2823-2013; Sabitov, Zhaxylyk/P-7576-2014; Tarlykov,
Pavel/C-2587-2012
OI Sabitov, Zhaxylyk/0000-0001-7186-156X; Tarlykov,
Pavel/0000-0003-2075-307X
FU Ministry of Education and Science of the Republic of Kazakhstan
[1.04.01]; Russian Foundation for Basic Research [12-04-90915]
FX Funding received from the Ministry of Education and Science of the
Republic of Kazakhstan, grant No. 1.04.01. This study was also partially
funded by Russian Foundation for Basic Research, grant 12-04-90915.
NR 28
TC 6
Z9 6
U1 0
U2 16
PU MEDICINSKA NAKLADA
PI ZAGREB
PA VLASKA 69, HR-10000 ZAGREB, CROATIA
SN 0353-9504
EI 1332-8166
J9 CROAT MED J
JI Croat. Med. J.
PD FEB
PY 2013
VL 54
IS 1
BP 17
EP 24
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 140OZ
UT WOS:000318666100004
PM 23444242
ER
PT J
AU Kawamoto, EM
Scavone, C
Mattson, MP
Camandola, S
AF Kawamoto, E. M.
Scavone, C.
Mattson, M. P.
Camandola, S.
TI Curcumin Requires Tumor Necrosis Factor alpha Signaling to Alleviate
Cognitive Impairment Elicited by Lipopolysaccharide
SO NEUROSIGNALS
LA English
DT Article
DE Curcumin; Tumor necrosis factor alpha; Cognition; Inflammation;
Lipopolysaccharide
ID ADULT HIPPOCAMPAL NEUROGENESIS; ISCHEMIC BRAIN-INJURY; TOLL-LIKE
RECEPTORS; GLIAL TNF-ALPHA; ALZHEIMERS-DISEASE; MICE LACKING; SPATIAL
MEMORY; IN-VITRO; DEFICIENT MICE; KAPPA-B
AB A decline in cognitive ability is a typical feature of the normal aging process, and of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. Although their etiologies differ, all of these disorders involve local activation of innate immune pathways and associated inflammatory cytokines. However, clinical trials of anti-inflammatory agents in neurodegenerative disorders have been disappointing, and it is therefore necessary to better understand the complex roles of the inflammatory process in neurological dysfunction. The dietary phytochemical curcumin can exert anti-inflammatory, antioxidant and neuroprotective actions. Here we provide evidence that curcumin ameliorates cognitive deficits associated with activation of the innate immune response by mechanisms requiring functional tumor necrosis factor alpha receptor 2 (TNFR2) signaling. In vivo, the ability of curcumin to counteract hippocampus-dependent spatial memory deficits, to stimulate neuroprotective mechanisms such as upregulation of BDNF, to decrease glutaminase levels, and to modulate N-methyl-D-aspartate receptor levels was absent in mice lacking functional TNFRs. Curcumin treatment protected cultured neurons against glutamate-induced excitotoxicity by a mechanism requiring TNFR2 activation. Our results suggest the possibility that therapeutic approaches against cognitive decline designed to selectively enhance TNFR2 signaling are likely to be more beneficial than the use of anti-inflammatory drugs per se. Copyright (C) 2012 S. Karger AG, Basel
C1 [Kawamoto, E. M.; Mattson, M. P.; Camandola, S.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Scavone, C.] Univ Sao Paulo, Dept Pharmacol, Inst Biomed Sci, Sao Paulo, Brazil.
RP Camandola, S (reprint author), NIA, Neurosci Lab, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM camandolasi@mail.nih.gov
RI Kawamoto, Elisa/E-3485-2012
OI Kawamoto, Elisa/0000-0001-8637-414X
FU Intramural Research Program of the National Institute on Aging of the
National Institutes of Health; Program and Fundacao de Amparo a Pesquisa
do Estado de Sao Paulo-FAPESP
FX We thank E. Okun for advice on the behavioral testing procedures and S.
Rothman for assistance in preparing the manuscript for publication. This
research was supported by the Intramural Research Program of the
National Institute on Aging of the National Institutes of Health, and by
Program and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP.
NR 69
TC 8
Z9 8
U1 1
U2 7
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1424-862X
J9 NEUROSIGNALS
JI Neurosignals
PD FEB
PY 2013
VL 21
IS 1-2
BP 75
EP 88
DI 10.1159/000336074
PG 14
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology;
Neurosciences
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology;
Neurosciences & Neurology
GA 138EH
UT WOS:000318491000007
PM 22572473
ER
PT J
AU Kassab, E
Darwish, M
Timsah, Z
Liu, SH
Leppla, SH
Frankel, AE
Abi-Habib, RJ
AF Kassab, Elias
Darwish, Manal
Timsah, Zahra
Liu, ShiHui
Leppla, Stephen H.
Frankel, Arthur E.
Abi-Habib, Ralph J.
TI Cytotoxicity of Anthrax Lethal Toxin to Human Acute Myeloid Leukemia
Cells Is Nonapoptotic and Dependent on Extracellular Signal-Regulated
Kinase 1/2 Activity
SO TRANSLATIONAL ONCOLOGY
LA English
DT Article
ID ACUTE MYELOGENOUS LEUKEMIA; MELANOMA-CELLS; ACTIVATION; APOPTOSIS;
PATHWAYS; RECEPTOR; MEK; INACTIVATION; INHIBITION; CANCER
AB In this study, we attempt to target the mitogen-activated protein kinase (MAPK) pathway in acute myeloid leukemia (AML) cells using a recombinant anthrax lethal toxin (LeTx). LeTx consists of protective antigen (PrAg) and lethal factor (LF). PrAg binds cells, is cleaved by furin, oligomerizes, binds three to four molecules of LF, and undergoes endocytosis, releasing LF into the cytosol. LF cleaves MAPK kinases, inhibiting the MAPK pathway. We tested potency of LeTx on a panel of 11 human AML cell lines. Seven cell lines showed cytotoxic responses to LeTx. Cytotoxicity of LeTx was mimicked by the specific mitogen-activated protein/extracellular signal-regulated kinase kinase 1/2 (MEK1/2) inhibitor U0126, indicating that LeTx-induced cell death is mediated through the MEK1/2-extracellular signal-regulated kinase (ERK1/2) branch of the MAPK pathway. The four LeTx-resistant cell lines were sensitive to the phosphatidylinositol 3-kinase inhibitor LY294002. Co-treatment of AML cells with both LeTx and LY294002 did not lead to increased sensitivity, showing a lack of additive/synergistic effects when both pathways are inhibited. Flow cytometry analysis of MAPK pathway activation revealed the presence of phospho-ERK1/2 only in LeTx-sensitive cells. Staining for Annexin V/propidium iodide and active caspases showed an increase in double-positive cells and the absence of caspase activation following treatment, indicating that LeTx-induced cell death is caspase-independent and nonapoptotic. We have shown that a majority of AML cell lines are sensitive to the LF-mediated inhibition of the MAPK pathway. Furthermore, we have demonstrated that LeTx-induced cytotoxicity in AML cells is nonapoptotic and dependent on phospho-ERK1/2 levels.
C1 [Kassab, Elias; Darwish, Manal; Timsah, Zahra; Abi-Habib, Ralph J.] Lebanese Amer Univ, Sch Arts & Sci, Dept Nat Sci, Beirut 11022801, Lebanon.
[Liu, ShiHui; Leppla, Stephen H.] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Frankel, Arthur E.] Scott & White Mem Hosp & Clin, Canc Res Inst, Temple, TX 76508 USA.
RP Abi-Habib, RJ (reprint author), Lebanese Amer Univ, Sch Arts & Sci, Beirut 11022801, Lebanon.
EM ralph.abihabib@lau.edu.lb
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (Bethesda, MD)
FX This work was supported in part by the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases (Bethesda,
MD). The authors have no conflict of interest to declare.
NR 33
TC 5
Z9 5
U1 0
U2 5
PU NEOPLASIA PRESS
PI ANN ARBOR
PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648
USA
SN 1944-7124
J9 TRANSL ONCOL
JI Transl. Oncol.
PD FEB
PY 2013
VL 6
IS 1
BP 25
EP 32
DI 10.1593/tlo.12313
PG 8
WC Oncology
SC Oncology
GA 139YC
UT WOS:000318620200005
PM 23418614
ER
PT J
AU Yeganeh, B
Hashemi, M
de Serres, FJ
Los, MJ
Ghavami, S
AF Yeganeh, Behzad
Hashemi, Mohammad
de Serres, Fredrick J.
Los, Marek J.
Ghavami, Saeid
TI Different Faces of Hepatocellular Carcinoma as a Health Threat in 21st
Century
SO HEPATITIS MONTHLY
LA English
DT Editorial Material
DE Biological Markers; Alpha 1 Antitrypsin; lobaplatin; Aflatoxins;
Hepatitis B Virus; Hepatitis C
ID HEPATITIS-B; ALPHA-1-ANTITRYPSIN DEFICIENCY; LIVER-TRANSPLANTATION;
GENETIC EPIDEMIOLOGY; VIRAL-HEPATITIS; VIRUS-INFECTION; S100 PROTEINS;
PATHOGENESIS; LOBAPLATIN; CANCER
C1 [Yeganeh, Behzad; Ghavami, Saeid] Univ Manitoba, Dept Physiol, Winnipeg, MB, Canada.
[Hashemi, Mohammad] Zahedan Univ Med Sci, Cellular & Mol Res Ctr, Zahedan, Iran.
[Hashemi, Mohammad] Zahedan Univ Med Sci, Sch Med, Dept Clin Biochem, Zahedan, Iran.
[de Serres, Fredrick J.] NIEHS, Ctr Evaluat Risks Human Reprod, Chapel Hill, NC USA.
[Los, Marek J.] Linkoping Univ, Div Cell Biol, Dept Clin & Expt Med, Integrat Regenerat Med Ctr IGEN, Linkoping, Sweden.
[Ghavami, Saeid] Manitoba Inst Child Hlth, Winnipeg, MB, Canada.
[Ghavami, Saeid] Univ Manitoba, St Boniface Res Ctr, Winnipeg, MB, Canada.
RP Los, MJ (reprint author), Linkoping Univ, Div Cell Biol, Deptartment Clin & Expt Med, Integrat Regenerat Med Ctr IGEN, Linkoping, Sweden.
EM marek.los@liu.se; saeid.ghavami@gmail.com
RI Hashemi, Mohammad/H-2446-2016; Ghavami, Saeid/Q-8918-2016;
OI Hashemi, Mohammad/0000-0002-6074-7101; Los, Marek/0000-0001-9518-1411
NR 46
TC 3
Z9 3
U1 0
U2 4
PU KOWSAR PUBL
PI HOENSBROEK
PA PATERSWEG 22,, HOENSBROEK, LIMBURG 6431 GC, NETHERLANDS
SN 1735-143X
EI 1735-3408
J9 HEPAT MON
JI Hepat. Mon.
PD FEB
PY 2013
VL 13
IS 2
AR e9308
DI 10.5812/hepatmon.9308
PG 4
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 134BA
UT WOS:000318183500012
PM 23613688
ER
PT J
AU Das, C
Jaeger, A
Pohida, T
Morgan, N
Gottesman, M
AF Das, C.
Jaeger, A.
Pohida, T.
Morgan, N.
Gottesman, M.
TI Microfabricated Polymeric Vessel Mimetics for Oxygenation of 3-D Cancer
Cell Cultures
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO)
CY MAR 06-09, 2013
CL National Harbor, MD
SP Soc Surg Oncol (SSO)
C1 [Das, C.; Jaeger, A.; Pohida, T.; Morgan, N.; Gottesman, M.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD FEB
PY 2013
VL 20
SU 1
BP S110
EP S110
PG 1
WC Oncology; Surgery
SC Oncology; Surgery
GA 133XR
UT WOS:000318174700320
ER
PT J
AU Golas, BJ
Magge, D
Zureikat, AH
Zeh, HJ
Alexander, HR
Libutti, SK
Royal, RE
Holtzman, MP
Hughes, MS
Turaga, KK
Pappas, SG
Gamblin, T
Bartlett, DL
Pingpank, JF
AF Golas, B. J.
Magge, D.
Zureikat, A. H.
Zeh, H. J.
Alexander, H. R.
Libutti, S. K.
Royal, R. E.
Holtzman, M. P.
Hughes, M. S.
Turaga, K. K.
Pappas, S. G.
Gamblin, T.
Bartlett, D. L.
Pingpank, J. F.
TI Analysis of Toxicity and Outcomes in Patients Undergoing Hyperthermic
Isolated Hepatic Perfusion with Melphalan for Metastatic Melanoma to the
Liver
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO)
CY MAR 06-09, 2013
CL National Harbor, MD
SP Soc Surg Oncol (SSO)
C1 [Golas, B. J.; Magge, D.; Zureikat, A. H.; Zeh, H. J.; Holtzman, M. P.; Bartlett, D. L.; Pingpank, J. F.] Univ Pittsburgh, Pittsburgh, PA USA.
[Hughes, M. S.] NCI, Surg Branch, Bethesda, MD 20892 USA.
[Alexander, H. R.] Univ Maryland, Baltimore, MD 21201 USA.
[Royal, R. E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Libutti, S. K.] Albert Einstein Montefiore Med Ctr, New York, NY USA.
[Turaga, K. K.; Pappas, S. G.; Gamblin, T.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD FEB
PY 2013
VL 20
SU 1
BP S20
EP S20
PG 1
WC Oncology; Surgery
SC Oncology; Surgery
GA 133XR
UT WOS:000318174700041
ER
PT J
AU Mamounas, EP
Tang, G
Paik, S
Baehner, FL
Liu, Q
Jeong, J
Kim, S
Butler, SM
Jamshidian, F
Cherbavaz, DB
Sing, AP
Shak, S
Julian, TB
Lembersky, BC
Wickerham, DL
Costantino, JP
Wolmark, N
AF Mamounas, E. P.
Tang, G.
Paik, S.
Baehner, F. L.
Liu, Q.
Jeong, J.
Kim, S.
Butler, S. M.
Jamshidian, F.
Cherbavaz, D. B.
Sing, A. P.
Shak, S.
Julian, T. B.
Lembersky, B. C.
Wickerham, D. L.
Costantino, J. P.
Wolmark, N.
TI The 21-gene Recurrence Score (RS) Predicts Risk of Loco-regional
Recurrence (LRR) in Node (+), ER (+) Breast Cancer (BC) after Adjuvant
Chemotherapy and Tamoxifen: Results from NSABP B-28
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO)
CY MAR 06-09, 2013
CL National Harbor, MD
SP Soc Surg Oncol (SSO)
C1 [Mamounas, E. P.] NSABP, Operat Ctr, Canton, OH USA.
[Mamounas, E. P.] NSABP, Biostat Ctr, Canton, OH USA.
[Mamounas, E. P.] Aultman Hosp, Canton, OH USA.
[Tang, G.; Paik, S.; Liu, Q.; Jeong, J.; Kim, S.; Julian, T. B.; Lembersky, B. C.; Wickerham, D. L.; Costantino, J. P.; Wolmark, N.] NSABP, Pittsburgh, PA USA.
[Tang, G.; Liu, Q.; Jeong, J.; Costantino, J. P.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Baehner, F. L.; Butler, S. M.; Jamshidian, F.; Cherbavaz, D. B.; Sing, A. P.; Shak, S.] Genom Hlth Inc, Redwood City, CA USA.
[Julian, T. B.; Wickerham, D. L.; Wolmark, N.] Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
[Lembersky, B. C.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
NR 0
TC 7
Z9 7
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD FEB
PY 2013
VL 20
SU 1
BP S6
EP S6
PG 1
WC Oncology; Surgery
SC Oncology; Surgery
GA 133XR
UT WOS:000318174700003
ER
PT J
AU Weisbrod, A
Kitano, M
Thomas, F
Williams, D
Gulati, N
Gesuwan, K
Liu, Y
Venzon, D
Venkatesan, A
Yao, J
Libutti, SK
Nilubol, N
Kebebew, E
AF Weisbrod, A.
Kitano, M.
Thomas, F.
Williams, D.
Gulati, N.
Gesuwan, K.
Liu, Y.
Venzon, D.
Venkatesan, A.
Yao, J.
Libutti, S. K.
Nilubol, N.
Kebebew, E.
TI Pancreatic Neuroendocrine Tumors in Von Hippel Lindau Syndrome: An
Assessment of Tumor Growth and Radiographic Density
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 66th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO)
CY MAR 06-09, 2013
CL National Harbor, MD
SP Soc Surg Oncol (SSO)
C1 [Thomas, F.; Williams, D.; Gulati, N.; Gesuwan, K.; Liu, Y.; Venzon, D.; Venkatesan, A.; Yao, J.; Nilubol, N.; Kebebew, E.] NIH, Bethesda, MD 20892 USA.
[Weisbrod, A.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[Kitano, M.; Libutti, S. K.] Montefiore Med Ctr, Bronx, NY 10467 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD FEB
PY 2013
VL 20
SU 1
BP S83
EP S84
PG 2
WC Oncology; Surgery
SC Oncology; Surgery
GA 133XR
UT WOS:000318174700233
ER
PT J
AU Boyce, CA
Maholmes, V
AF Boyce, Cheryl Anne
Maholmes, Valerie
TI Attention to the Neglected: Prospects for Research on Child Neglect for
the Next Decade
SO CHILD MALTREATMENT
LA English
DT Editorial Material
DE child neglect; child health; children; families
ID INITIAL PAPERS; SPECIAL-ISSUE; PROJECTS; NIH
AB In 1997, the National Institutes of Health within the United States Department of Health and Human Services reviewed the state of its research on child abuse and neglect (US Department of Health and Human Services, National Institutes of Health, 1997). The findings suggested that although neglect was the most frequent type of child maltreatment, research studies were lacking. Through an unprecedented partnership across federal funding agencies for research on child neglect, research was encouraged in several areas. Over the past fifteen years, consortia of researchers have continued to increase our knowledge of child neglect and to shape the field. Nonetheless, challenges for research on child neglect remain, including the changing demographics of the nation and health disparities. Evidenced-based early interventions and treatments may be an opportunity for prevention of child neglect and improving child welfare services, particularly in an era of health care reform. Developmental researchers across the translational pipeline are encouraged to integrate child neglect research in future studies to inform prevention, treatment and policy efforts for the improved health and well-being of children, families and communities.
C1 [Boyce, Cheryl Anne] NIDA, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Maholmes, Valerie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Hlth & Human Serv, NIH, Bethesda, MD USA.
RP Boyce, CA (reprint author), NIDA, Dept Hlth & Human Serv, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA.
EM cboyce@mail.nih.gov
NR 27
TC 4
Z9 4
U1 0
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1077-5595
J9 CHILD MALTREATMENT
JI Child Maltreatment
PD FEB
PY 2013
VL 18
IS 1
SI SI
BP 65
EP 68
DI 10.1177/1077559513480426
PG 4
WC Family Studies; Social Work
SC Family Studies; Social Work
GA 132BW
UT WOS:000318043800007
PM 23444199
ER
PT J
AU Shabalina, SA
Spiridonov, NA
Kashina, A
AF Shabalina, Svetlana A.
Spiridonov, Nikolay A.
Kashina, Anna
TI Sounds of silence: synonymous nucleotides as a key to biological
regulation and complexity
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID RNA SECONDARY STRUCTURE; EUKARYOTIC MESSENGER-RNAS;
ZIPCODE-BINDING-PROTEIN; CODON USAGE BIAS; RETICULOCYTE TRANSFER-RNA;
GENOME-WIDE MEASUREMENT; BETA-ACTIN SYNTHESIS; ESCHERICHIA-COLI;
GENE-EXPRESSION; CODING REGIONS
AB Messenger RNA is a key component of an intricate regulatory network of its own. It accommodates numerous nucleotide signals that overlap protein coding sequences and are responsible for multiple levels of regulation and generation of biological complexity. A wealth of structural and regulatory information, which mRNA carries in addition to the encoded amino acid sequence, raises the question of how these signals and overlapping codes are delineated along non-synonymous and synonymous positions in protein coding regions, especially in eukaryotes. Silent or synonymous codon positions, which do not determine amino acid sequences of the encoded proteins, define mRNA secondary structure and stability and affect the rate of translation, folding and post-translational modifications of nascent polypeptides. The RNA level selection is acting on synonymous sites in both prokaryotes and eukaryotes and is more common than previously thought. Selection pressure on the coding gene regions follows three-nucleotide periodic pattern of nucleotide base-pairing in mRNA, which is imposed by the genetic code. Synonymous positions of the coding regions have a higher level of hybridization potential relative to non-synonymous positions, and are multifunctional in their regulatory and structural roles. Recent experimental evidence and analysis of mRNA structure and interspecies conservation suggest that there is an evolutionary tradeoff between selective pressure acting at the RNA and protein levels. Here we provide a comprehensive overview of the studies that define the role of silent positions in regulating RNA structure and processing that exert downstream effects on proteins and their functions.
C1 [Shabalina, Svetlana A.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20984 USA.
[Spiridonov, Nikolay A.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA.
[Kashina, Anna] Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA.
RP Shabalina, SA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20984 USA.
EM shabalin@ncbi.nlm.nih.gov
RI Shabalina, Svetlana/N-8939-2013; Spiridonov, Nikolay/B-6287-2014
OI Shabalina, Svetlana/0000-0003-2272-7473;
FU DHHS (NIH, National Library of Medicine); NIH [R01HL084419]
FX DHHS (NIH, National Library of Medicine) intramural funds; NIH
[R01HL084419 to A.K.]. Funding for open access charge: DHHS (NIH,
National Library of Medicine) intramural funds.
NR 221
TC 65
Z9 67
U1 0
U2 39
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD FEB
PY 2013
VL 41
IS 4
BP 2073
EP 2094
DI 10.1093/nar/gks1205
PG 22
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 132IV
UT WOS:000318062000009
PM 23293005
ER
PT J
AU Aduri, R
Briggs, KT
Gorelick, RJ
Marino, JP
AF Aduri, Raviprasad
Briggs, Katharine T.
Gorelick, Robert J.
Marino, John P.
TI Molecular determinants of HIV-1 NCp7 chaperone activity in maturation of
the HIV-1 dimerization initiation site
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; NUCLEOCAPSID PROTEIN NCP7; ZINC-FINGER
STRUCTURES; PLUS-STRAND TRANSFER; PRIMER BINDING-SITE; RNA IN-VITRO;
GENOMIC RNA; REVERSE TRANSCRIPTION; KISSING-LOOP; SECONDARY STRUCTURE
AB Human immunodeficiency virus genome dimerization is initiated through an RNA-RNA kissing interaction formed via the dimerization initiation site (DIS) loop sequence, which has been proposed to be converted to a more thermodynamically stable linkage by the viral p7 form of the nucleocapsid protein (NC). Here, we systematically probed the role of specific amino acids of NCp7 in its chaperone activity in the DIS conversion using 2-aminopurine (2-AP) fluorescence and nuclear magnetic resonance spectroscopy. Through comparative analysis of NCp7 mutants, the presence of positively charged residues in the N-terminus was found to be essential for both helix destabilization and strand transfer functions. It was also observed that the presence and type of the Zn finger is important for NCp7 chaperone activity, but not the order of the Zn fingers. Swapping single aromatic residues between Zn fingers had a significant effect on NCp7 activity; however, these mutants did not exhibit the same activity as mutants in which the order of the Zn fingers was changed, indicating a functional role for other flanking residues. RNA chaperone activity is further correlated with NCp7 structure and interaction with RNA through comparative analysis of nuclear magnetic resonance spectra of NCp7 variants, and complexes of these proteins with the DIS dimer.
C1 [Aduri, Raviprasad; Briggs, Katharine T.; Marino, John P.] Univ Maryland, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA.
[Aduri, Raviprasad; Briggs, Katharine T.; Marino, John P.] NIST, Rockville, MD 20850 USA.
[Gorelick, Robert J.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Marino, JP (reprint author), Univ Maryland, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA.
EM john.marino@nist.gov
FU National Institutes of Health [GM 59107]; National Cancer Institute,
National Institutes of Health [HHSN261200800001E]; SAIC-Frederick, Inc.;
National Institutes of Health graduate training fellowship; NMR
instrumentation at IBBR; W.M. Keck Foundation; National Institutes of
Health; National Institute of Standards and Technology; NIST intramural
funds
FX National Institutes of Health [GM 59107 to J.P.M. in part]; National
Cancer Institute, National Institutes of Health, under contract
[HHSN261200800001E] with SAIC-Frederick, Inc. (to R.J.G.); National
Institutes of Health graduate training fellowship to UMd (to K. T. B.);
NMR instrumentation at IBBR with support from the W.M. Keck Foundation,
the National Institutes of Health and the National Institute of
Standards and Technology. Funding for open access charge: NIST
intramural funds.
NR 78
TC 1
Z9 1
U1 2
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD FEB
PY 2013
VL 41
IS 4
BP 2565
EP 2580
DI 10.1093/nar/gks1350
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 132IV
UT WOS:000318062000046
PM 23275531
ER
PT J
AU Chan, L
Chin, LMK
Kennedy, M
Woolstenhulme, JG
Nathan, SD
Weinstein, AA
Connors, G
Weir, NA
Drinkard, B
Lamberti, J
Keyser, RE
AF Chan, Leighton
Chin, Lisa M. K.
Kennedy, Michelle
Woolstenhulme, Joshua G.
Nathan, Steven D.
Weinstein, Ali A.
Connors, Gerilynn
Weir, Nargues A.
Drinkard, Bart
Lamberti, James
Keyser, Randall E.
TI Benefits of Intensive Treadmill Exercise Training on Cardiorespiratory
Function and Quality of Life in Patients With Pulmonary Hypertension
SO CHEST
LA English
DT Article
ID 6-MINUTE WALK TEST; CLINICAL-PRACTICE GUIDELINES; CHRONIC HEART-FAILURE;
ARTERIAL-HYPERTENSION; GAS-EXCHANGE; RISK STRATIFICATION; CONSENSUS
DOCUMENT; PHYSICAL-ACTIVITY; TASK-FORCE; DISEASE
AB Background: Pulmonary hypertension (PH) restricts the ability to engage in physical activity and decreases longevity. We examined the impact of aerobic exercise training on function and quality of life in patients with World Health Organization group 1 PH.
Methods: Patients were randomized to a 10-week education only (EDU) or education/exercise combined (EXE) group. The exercise program consisted of 24-30 sessions of treadmill walking for 30-45 min per session at 70% to 80% of heart rate reserve. Outcome variables included changes in 6-min walk test (6MWT) distance, time to exercise intolerance, peak work rate (WR) from a cardiopulmonary treadmill test, and quality-of-life measures, including the Short Form Health Survey, version 2 (SF-36v2) and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR).
Results: Data are presented as mean +/- SD. Twenty-three women (age, 54 +/- 11 years; BMI, 31 +/- 7 kg/m(2)) were randomized to the EDU (n = 13) or EXE (n = 10) groups. Following 10 weeks of intervention, patients in the EXE group demonstrated an improvement in 6MWT distance (56 +/- 45 m; P = .002), increased time to exercise intolerance (1.9 +/- 1.3 min; P = .001), and peak WR (26 +/- 23 W; P = .004). Additionally, the EXE group scored significantly (P < .050) better on six of the eight scales on SF-36v2, and five of the six scales on CAMPHOR. In contrast, no significant improvement was observed for any of the outcome measures following EDU. No adverse events were noted in either group.
Conclusion: Ten weeks of brisk treadmill walking improved 6MWT distance, cardiorespiratory function, and patient-reported quality of life in female patients with group 1 PH. Trial registry: ClinicalTrials.gov; No.: NCT00678821; URL: clinicaltrials.gov CHEST 2013; 143(2):333-343
C1 [Chan, Leighton; Chin, Lisa M. K.; Kennedy, Michelle; Woolstenhulme, Joshua G.; Drinkard, Bart; Keyser, Randall E.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA.
[Woolstenhulme, Joshua G.; Weinstein, Ali A.; Keyser, Randall E.] George Mason Univ, Dept Rehabil Sci, Fairfax, VA 22030 USA.
[Nathan, Steven D.; Weir, Nargues A.; Lamberti, James] Inova Fairfax Hosp, Dept Med, Falls Church, VA USA.
[Connors, Gerilynn] Inova Fairfax Hosp, Pulm Rehabil Ctr, Falls Church, VA USA.
RP Chan, L (reprint author), NIH, Dept Rehabil Med, Ctr Clin, Bldg 10,Room 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA.
EM chanle@cc.nih.gov
RI Chin, Lisa/O-4706-2014
OI Chin, Lisa/0000-0002-0178-739X
FU US National Institutes of Health [1 Z01 CL060068-05 CC]; Actelion
Pharmaceuticals US Inc; Gilead Sciences Inc; United Therapeutics
Corporation
FX This work was supported by the US National Institutes of Health
[Intramural Funds 1 Z01 CL060068-05 CC].; The authors have reported to
CHEST the following conflicts of interest: Dr Nathan has received
research funding, has been. a consultant, and is on the speaker's bureau
for Actelion Pharmaceuticals US Inc, Gilead Sciences Inc, and United
Therapeutics Corporation. Dr Lamberti is on the speaker's bureau for
GlaxoSmithKline plc and Boehringer Ingelheim GmbH. The remaining authors
have reported that no potential conflicts of interest exist with any
companies/organizations whose products or services may be discussed in
this article.
NR 57
TC 52
Z9 54
U1 3
U2 19
PU AMER COLL CHEST PHYSICIANS
PI GLENVIEW
PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA
SN 0012-3692
J9 CHEST
JI Chest
PD FEB
PY 2013
VL 143
IS 2
BP 333
EP 343
DI 10.1378/chest.12-0993
PG 11
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 129VC
UT WOS:000317871100012
PM 22922554
ER
PT J
AU Lorenzo, MMG
Fenton, MJ
AF Lorenzo, Margarita M. Gomez
Fenton, Matthew J.
TI Immunobiology of Influenza Vaccines
SO CHEST
LA English
DT Article
ID MEMORY B-CELLS; PANDEMIC INFLUENZA; SYSTEMS BIOLOGY; IMMUNE-RESPONSE;
SEASONAL INFLUENZA; ANTIBODY-RESPONSES; H5N1 INFLUENZA; VIRUS-VACCINES;
A VIRUS; VACCINATION
AB Vaccination is the primary strategy for prevention and control of influenza. The surface hemagglutinin (HA) protein of the influenza virus contains two structural elements (head and stalk) that differ in their potential utility as vaccine targets. The head of the HA protein is the primary target of antibodies that confer protective immunity to influenza viruses. The underlying health status, age, and gene polymorphisms of vaccine recipients and, just as importantly, the extent of the antigenic match between the viruses in the vaccine and those that are circulating modulate influenza vaccine protection. Vaccine adjuvants and live attenuated influenza vaccine improve the breadth of immunity to seasonal and pandemic virus strains. Eliciting antibodies against, the conserved HA stem region that cross-react with HAs within influenza virus types or subtypes would allow for the development of a universal influenza vaccine. The highly complex network of interactions generated after influenza infection and vaccination can be studied with the use of systems biology tools, such as DNA microarray chips. The use of systems vaccinology has allowed for the generation of gene expression signatures that represent key transcriptional differences between asymptomatic and symptomatic host responses to influenza infection. Additionally, the use of systems vaccinology tools have resulted in the identification of novel surrogate gene markers that are predictors of the magnitude of host responses to vaccines, which is critical to both vaccine development and public health. Identifying associations between variations in vaccine immune responses and gene polymorphisms is critical in the development of universal influenza vaccines. CHEST 2013; 143(2):502-510
C1 [Lorenzo, Margarita M. Gomez; Fenton, Matthew J.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Lorenzo, MMG (reprint author), NIAID, Asthma Allergy & Airway Biol Branch, NIH, Dept Hlth & Human Serv, 6610 Rockledge Dr,Room 6508,Mail Stop 6601, Bethesda, MD 20892 USA.
EM gomezmm@niaid.nih.gov
NR 75
TC 6
Z9 7
U1 1
U2 13
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD FEB
PY 2013
VL 143
IS 2
BP 502
EP 510
DI 10.1378/chest.12-1711
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 129VC
UT WOS:000317871100033
ER
PT J
AU Davidov, O
Peddada, S
AF Davidov, Ori
Peddada, Shyamal
TI THE LINEAR STOCHASTIC ORDER AND DIRECTED INFERENCE FOR MULTIVARIATE
ORDERED DISTRIBUTIONS
SO ANNALS OF STATISTICS
LA English
DT Article
DE Nonparametric tests; order-restricted statistical inference; stochastic
order relations
ID N-BOOTSTRAP; ESTIMATOR
AB Researchers are often interested in drawing inferences regarding the order between two experimental groups on the basis of multivariate response data. Since standard multivariate methods are designed for two-sided alternatives, they may not be ideal for testing for. order between two groups. In this article we introduce the notion of the linear stochastic order and investigate its properties. Statistical theory and methodology are developed to both estimate the direction which best separates two arbitrary ordered distributions and to test for order between the two groups. The new methodology generalizes Roy's classical largest root test to the nonparametric setting and is applicable to random vectors with discrete and/or continuous components. The proposed methodology is illustrated using data obtained from a 90-day pre-chronic rodent cancer bioassay study conducted by the National Toxicology Program (NTP).
C1 [Davidov, Ori] Univ Haifa, Dept Stat, IL-31905 Haifa, Israel.
[Peddada, Shyamal] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Davidov, O (reprint author), Univ Haifa, Dept Stat, IL-31905 Haifa, Israel.
EM davidov@stat.haifa.ac.il; peddada@niehs.nih.gov
FU Israeli Science Foundation [875/09]; Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences [Z01
ES101744-04]
FX Supported in part by the Israeli Science Foundation Grant No 875/09.;
Supported in part by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences (Z01 ES101744-04).
NR 38
TC 3
Z9 3
U1 1
U2 10
PU INST MATHEMATICAL STATISTICS
PI CLEVELAND
PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA
SN 0090-5364
J9 ANN STAT
JI Ann. Stat.
PD FEB
PY 2013
VL 41
IS 1
BP 1
EP 40
DI 10.1214/12-AOS1062
PG 40
WC Statistics & Probability
SC Mathematics
GA 124GG
UT WOS:000317451200001
PM 23543786
ER
PT J
AU Tang, ZW
Qian, M
Ho, M
AF Tang, Zhewei
Qian, Min
Ho, Mitchell
TI The Role of Mesothelin in Tumor Progression and Targeted Therapy
SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
LA English
DT Article
DE Antibody dependent cell mediated cytotoxicity/ADCC; Apoptosis; Cell
surface proteins; Cell survival/proliferation; Complement dependent
cytotoxicity/CDC; Human monoclonal antibodies; Immunotoxin; Mesothelin;
MORAb-009/amatuximab; MUC16/CA125; NF-kappa B; PI3K/Akt; SS1P
ID CANCER CELL-PROLIFERATION; HUMAN MONOCLONAL-ANTIBODY; PANCREATIC-CANCER;
HIGH-AFFINITY; OVARIAN-CANCER; PHASE-I; RECOMBINANT IMMUNOTOXIN;
OVEREXPRESSION; IMMUNOTHERAPY; EXPRESSION
AB Mesothelin, a glycosylphosphatidylinositol (GPI) anchored cell surface protein, is a potential target for antibody-based cancer therapy due to its high expression in mesothelioma, ovarian cancer, pancreatic cancer, cholangiocarcinoma and other cancers. The SS1P immunotoxin and MORAb-009 (amatuximab), a chimeric monoclonal antibody, are currently being evaluated in clinical trials. In this review, we discuss the role of mesothelin in cancer progression and provide new insights into mesothelin-targeted cancer therapy. Recent studies highlight three mechanisms by which mesothelin plays a role in cancer progression. First, mesothelin may aid in the peritoneal implantation and metastasis of tumors through its interaction with mucin MUC16 (also known as CA125). Second, mesothelin may promote cancer cell survival and proliferation via the NF-kappa B signaling pathway. Finally, mesothelin expression promotes resistance to certain chemotherapy drugs such as TNF-alpha, paclitaxel, and a combination of platinum and cyclophosphamide. However, its cancer-specific expression makes mesothelin a potential target for monoclonal antibody therapy. New human monoclonal antibodies targeting mesothelin have been isolated by phage display technology and may provide opportunities for novel cancer therapy.
C1 [Tang, Zhewei; Qian, Min] E China Normal Univ, Sch Life Sci, Inst Biomed Sci, Shanghai 200062, Peoples R China.
[Tang, Zhewei; Ho, Mitchell] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Ho, M (reprint author), NCI, Antibody Therapy Sect, Mol Biol Lab, 37 Convent Dr,Room 5002C, Bethesda, MD 20892 USA.
EM homi@mail.nih.gov
RI Ho, Mitchell/F-5059-2015
FU National Institutes of Health (NIH), NCI, Center for Cancer Research;
NCI Director's Intramural Innovation Award for Principal Investigators;
Ovarian Cancer Research Fund Individual Investigator Award; Mesothelioma
Applied Research Foundation Craig Kozicki Memorial Grant
FX This research is supported by the Intramural Research Program of the
National Institutes of Health (NIH), NCI, Center for Cancer Research.
Dr. Mitchell Ho is also supported by the NCI Director's Intramural
Innovation Award for Principal Investigators, an Ovarian Cancer Research
Fund Individual Investigator Award, and a Mesothelioma Applied Research
Foundation Craig Kozicki Memorial Grant. Dr. Ho is a Zi-jiang Lecture
Professor of East China Normal University. Zhewei Tang is in the
Graduate Partnerships Program of the NIH. 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 authors have no conflict of interest directly
relevant to the content of this review. We thank the NIH Fellows
Editorial Board and Yen Phung (NCI) for editorial assistance.
NR 40
TC 32
Z9 34
U1 1
U2 20
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1871-5206
J9 ANTI-CANCER AGENT ME
JI Anti-Cancer Agents Med. Chem.
PD FEB
PY 2013
VL 13
IS 2
BP 276
EP 280
PG 5
WC Oncology; Chemistry, Medicinal
SC Oncology; Pharmacology & Pharmacy
GA 129NV
UT WOS:000317848800014
PM 22721387
ER
PT J
AU Zheng, P
Baibakov, B
Wang, XH
Dean, J
AF Zheng, Ping
Baibakov, Boris
Wang, Xi-hong
Dean, Jurrien
TI PtdIns(3,4,5)P-3 is constitutively synthesized and required for spindle
translocation during meiosis in mouse oocytes
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE PtdIns(3,4,5)P-3; Oocyte meiosis; Spindle translocation; Filamentous
actin; Cdc42
ID MATERNAL EFFECT GENE; MEIOTIC SPINDLE; ASYMMETRIC DIVISION;
PHOSPHATIDYLINOSITOL 3-KINASE; GROWTH-FACTOR; RHO-GTPASES; ACTIN;
FORMIN-2; PROTEIN; WORTMANNIN
AB Prior to ovulation, mammalian oocytes complete their first meiotic division and arrest at metaphase II. During this marked asymmetric cell division, the meiotic spindle moves dramatically from the center of the oocyte to the cortex to facilitate segregation of half of its chromosomal content into the diminutive first polar body. Recent investigations have documented crucial roles for filamentous actin (F-actin) in meiotic spindle translocation. However, the identity of the upstream regulators responsible for these carefully orchestrated movements has remained elusive. Utilizing fluorescently tagged probes and time-lapse confocal microscopy, we document that phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P-3] is constitutively synthesized with spatial and temporal dynamics similar to that of F-actin and Formin 2 (Fmn2). Blockage of PtdIns(3,4,5) P-3 synthesis by LY294002, a specific inhibitor of phosphoinositide 3-kinase (PI3K), disrupts cytoplasmic F-actin organization and meiotic spindle migration to the cortex. F-actin nucleator Fmn2 and Rho GTPase Cdc42 play roles in mediating the effect of PtdIns(3,4,5)P-3 on F-actin assembly. Moreover, the spatial and temporal dynamics of PtdIns(3,4,5)P-3 is impaired by depletion of MATER or Filia, two oocyte proteins encoded by maternal effect genes. Thus, PtdIns(3,4,5)P-3 is synthesized during meiotic maturation and acts upstream of Cdc42 and Fmn2, but downstream of MATER/Filia proteins to regulate the F-actin organization and spindle translocation to the cortex during mouse oocyte meiosis.
C1 [Zheng, Ping] Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China.
[Zheng, Ping; Wang, Xi-hong] Chinese Acad Sci, Kunming Inst Zool, Yunnan Key Lab Anim Reprod Biol, Kunming 650223, Yunnan, Peoples R China.
[Baibakov, Boris; Dean, Jurrien] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Zheng, P (reprint author), Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China.
EM zhengp@mail.kiz.ac.cn; jurrien@helix.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, USA; Natural Science Foundation of China
[31071274]
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, USA (to J. D.); and the Natural Science
Foundation of China [grant number 31071274 to P. Zheng]. Deposited in
PMC for release after 12 months.
NR 47
TC 9
Z9 9
U1 0
U2 9
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD FEB 1
PY 2013
VL 126
IS 3
BP 715
EP 721
DI 10.1242/jcs.118042
PG 7
WC Cell Biology
SC Cell Biology
GA 121YN
UT WOS:000317281700002
PM 23264738
ER
PT J
AU Hayton, K
Dumoulin, P
Henschen, B
Liu, A
Papakrivos, J
Wellems, TE
AF Hayton, Karen
Dumoulin, Peter
Henschen, Bruce
Liu, Anna
Papakrivos, Janni
Wellems, Thomas E.
TI Various PfRH5 polymorphisms can support Plasmodium falciparum invasion
into the erythrocytes of owl monkeys and rats
SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY
LA English
DT Article
DE Malaria; Virulence; Aotus nancymaae; Sialic acid; Rattus norvegicus; Mus
musculus
ID RETICULOCYTE BINDING-PROTEINS; HUMAN MALARIA PARASITES; RECEPTOR
HETEROGENEITY; MEROZOITE PROTEINS; HOST ERYTHROCYTES; GLYCOPHORIN-B;
LIGAND; VIVAX; ACID; SPECIFICITY
AB Aotus nancymaae, the owl monkey, provides a useful laboratory model for research to develop drugs and vaccines against human falciparum malaria; however, many Plasmodium falciparum parasites are unable to invade A. nancymaae erythrocytes, rendering the parasites noninfective to the monkeys. In previous work, we identified a key polymorphism that determined the inheritance of erythrocyte invasion in a genetic cross of two P. falciparum clones that were virulent (GB4) or noninfective (7G8) to A. nancymaae. This polymorphism, an isoleucine-to-lysine polymorphism at position 204 (I204K) of the GB4 erythrocyte binding protein PfRH5, was nevertheless not found in several other P. falciparum lines that could also invade A. nancymaae erythrocytes. Alternative PfRH5 polymorphisms occur at different positions in these virulent parasites, and additional polymorphisms are found in P. falciparum parasites that cannot infect A. nancymaae. By allelic replacement methods, we have introduced the polymorphisms of these A. nancymaae-virulent or noninfective parasites at codons 204, 347, 358, 362, 410, and 429 of the endogenous PfRH5 gene in the noninfective 7G8 line. 7G8 transformants expressing the polymorphisms of the A. nancymaae-virulent parasites show neuraminidase-sensitive (sialic acid-dependent) invasion into the monkey erythrocytes, whereas 7G8 transformants expressing the PfRH5 alleles of noninfective parasites show little or no invasion of these erythrocytes. Parasites harboring PfRH5 polymorphisms 204K or 204R are also able to invade rat erythrocytes and are differentially sensitive to the removal of surface sialic acids by neuraminidase. These studies offer insights into the PfRH5 receptor-binding domain and interactions that support the invasion of various primate and rodent erythrocytes by P. falciparum. Published by Elsevier B.V.
C1 [Hayton, Karen; Dumoulin, Peter; Henschen, Bruce; Liu, Anna; Papakrivos, Janni; Wellems, Thomas E.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Wellems, TE (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM twellems@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX We thank Lynn Lambert, Angela Lunger, and Sachy Orr-Gonzalez for the
provision of blood samples; Osamu Kaneko for helpful discussions; and
NIAID intramural editor Brenda Marshall for assistance. This research
was supported by the Division of Intramural Research, National Institute
of Allergy and Infectious Diseases, National Institutes of Health.
NR 62
TC 15
Z9 15
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-6851
J9 MOL BIOCHEM PARASIT
JI Mol. Biochem. Parasitol.
PD FEB
PY 2013
VL 187
IS 2
BP 103
EP 110
DI 10.1016/j.molbiopara.2012.12.005
PG 8
WC Biochemistry & Molecular Biology; Parasitology
SC Biochemistry & Molecular Biology; Parasitology
GA 120LW
UT WOS:000317172800005
PM 23305874
ER
PT J
AU Shi, K
Parekh, VI
Roy, S
Desai, SS
Agarwal, SK
AF Shi, Kerong
Parekh, Vaishali I.
Roy, Swarnava
Desai, Shruti S.
Agarwal, Sunita K.
TI The embryonic transcription factor Hlxb9 is a menin interacting partner
that controls pancreatic beta-cell proliferation and the expression of
insulin regulators
SO ENDOCRINE-RELATED CANCER
LA English
DT Article
DE multiple endocrine neoplasias; gene regulation; gene expression; islet
cells
ID MISSENSE MUTANTS; HOMEOBOX GENE; MLL; MICE; SECRETION; PROTEINS;
AGENESIS; JUND; SUPPRESSION; LEUKEMIA
AB The multiple endocrine neoplasia type 1 (MEN1) syndrome is caused by germline mutations in the MEN1 gene encoding menin, with tissue-specific tumors of the parathyroids, anterior pituitary, and enteropancreatic endocrine tissues. Also, 30-40% of sporadic pancreatic endocrine tumors show somatic MEN1 gene inactivation. Although menin is expressed in all cell types of the pancreas, mouse models with loss of menin in either pancreatic alpha-cells, or beta-cells, or total pancreas develop beta-cell-specific endocrine tumors (insulinomas). Loss of widely expressed tumor suppressor genes may produce tissue-specific tumors by reactivating one or more embryonic-specific differentiation factors. Therefore, we determined the effect of menin overexpression or knockdown on the expression of beta-cell differentiation factors in a mouse b-cell line (MIN6). We show that the beta-cell differentiation factor Hlxb9 is posttranscriptionally upregulated upon menin knockdown, and it interacts with menin. Hlxb9 reduces cell proliferation and causes apoptosis in the presence of menin, and it regulates genes that modulate insulin level. Thus, upon menin loss or from other causes, dysregulation of Hlxb9 predicts a possible combined mechanism for beta-cell proliferation and insulin production in insulinomas. These observations help to understand how a ubiquitously expressed protein such as menin might control tissue-specific tumorigenesis. Also, our findings identify Hlxb9 as an important factor for beta-cell proliferation and insulin regulation.
C1 [Shi, Kerong; Parekh, Vaishali I.; Roy, Swarnava; Desai, Shruti S.; Agarwal, Sunita K.] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Agarwal, SK (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Room 8C-101, Bethesda, MD 20892 USA.
EM sunitaa@mail.nih.gov
RI Agarwal, Sunita/D-1428-2016
OI Agarwal, Sunita/0000-0002-7557-3191
FU Division of Intramural Research of the National Institute of Diabetes
and Digestive and Kidney Diseases, Bethesda, Maryland, USA
FX This research was funded by the Division of Intramural Research of the
National Institute of Diabetes and Digestive and Kidney Diseases,
Bethesda, Maryland, USA.
NR 42
TC 9
Z9 9
U1 0
U2 2
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD FEB
PY 2013
VL 20
IS 1
BP 111
EP 122
DI 10.1530/ERC-12-0077
PG 12
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA 121RZ
UT WOS:000317263200012
PM 23419452
ER
PT J
AU Dallal, CM
Brinton, LA
Bauer, DC
Buist, DSM
Cauley, JA
Hue, TF
LaCroix, A
Tice, JA
Chia, VM
Falk, R
Pfeiffer, R
Pollak, M
Veenstra, TD
Xu, X
Lacey, JV
AF Dallal, Cher M.
Brinton, Louise A.
Bauer, Douglas C.
Buist, Diana S. M.
Cauley, Jane A.
Hue, Trisha F.
LaCroix, Andrea
Tice, Jeffrey A.
Chia, Victoria M.
Falk, Roni
Pfeiffer, Ruth
Pollak, Michael
Veenstra, Timothy D.
Xu, Xia
Lacey, James V., Jr.
CA B FIT Res Grp
TI Obesity-related hormones and endometrial cancer among postmenopausal
women: a nested case-control study within the B similar to FIT cohort
SO ENDOCRINE-RELATED CANCER
LA English
DT Article
DE endometrial cancer; adiponectin; leptin; obesity
ID FRACTURE INTERVENTION TRIAL; BODY-MASS-INDEX; BIOLOGICAL MECHANISMS;
VERTEBRAL FRACTURES; INSULIN SENSITIVITY; RANDOMIZED-TRIAL;
STEROID-HORMONES; ADIPOSE-TISSUE; ADIPONECTIN; RISK
AB Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case-control study, nested within the Breast and Bone Follow-up of the Fracture Intervention Trial (n = 15 595), we assessed pre-diagnostic serum leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin in relation to endometrial cancer among postmenopausal women. During the 10-year follow-up, 62 incident endometrial cases were identified and matched to 124 controls on age, geographical site, time of fasting blood draw at baseline (1992-1993), and trial participation status. Adipokines and C-peptide were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated via conditional logistic regression, with exposures categorized in tertiles (T). Multivariable models considered C-peptide, BMI (kg/m(2)), and estradiol (E2) as potential confounders. Endometrial cancer risk was significantly associated with higher leptin levels, adjusted for E2 and C-peptide (ORT3 (vs) (T1) = 2.96; 95% CI, 1.21-7.25; P trend < 0.01). After further adjustment for BMI, the estimates were attenuated and the positive trend was no longer statistically significant (ORT3 (vs) (T1) = 2.11; 95% CI, 0.69-6.44; P trend = 0.18). No significant associations were observed with adiponectin or HMW adiponectin and endometrial cancer. Our findings with leptin suggest that the leptin-BMI axis might increase endometrial cancer risk through mechanisms other than estrogen-driven proliferation. Continued exploration of these pathways in larger prospective studies may help elucidate mechanisms underlying observed obesity-endometrial cancer associations.
C1 [Dallal, Cher M.; Brinton, Louise A.; Chia, Victoria M.; Falk, Roni] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA.
[Dallal, Cher M.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Bethesda, MD 20852 USA.
[Bauer, Douglas C.; Tice, Jeffrey A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Buist, Diana S. M.] Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Cauley, Jane A.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Hue, Trisha F.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA.
[LaCroix, Andrea] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Pfeiffer, Ruth] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA.
[Pollak, Michael] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada.
[Veenstra, Timothy D.; Xu, Xia] SAIC Frederick Inc, Adv Technol Program, Lab Prote & Analyt Technol, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Lacey, James V., Jr.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA.
RP Dallal, CM (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Suite 550, Bethesda, MD 20852 USA.
EM cher.dallal@nih.gov
RI Brinton, Louise/G-7486-2015
OI Brinton, Louise/0000-0003-3853-8562
FU Merck Research Laboratories; National Cancer Institute [N02-CP-01019]
FX The original FIT study was funded by Merck Research Laboratories. B
similar to FIT was funded by the National Cancer Institute (contract
#N02-CP-01019).
NR 33
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U1 0
U2 5
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD FEB
PY 2013
VL 20
IS 1
BP 151
EP 160
DI 10.1530/ERC-12-0229
PG 10
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA 121RZ
UT WOS:000317263200015
PM 23222000
ER
PT J
AU Stratakis, CA
AF Stratakis, Constantine A.
TI Joy and discovery are inseparable from academic commitment
SO ENDOCRINE-RELATED CANCER
LA English
DT Editorial Material
ID PHOSPHODIESTERASE 11A4 PDE11A; ADRENOCORTICAL DISEASE; CUSHING-SYNDROME;
CARNEY COMPLEX; MUTATIONS; HYPERPLASIA; TUMORS
C1 [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Stratakis, Constantine A.] Program Dev Endocrinol & Genet, Sect Endocrinol & Genet SEGEN, Bethesda, MD 20892 USA.
[Stratakis, Constantine A.] NIH, Interinst Pediat Endocrinol Training Program, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
NR 18
TC 0
Z9 0
U1 0
U2 3
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD FEB
PY 2013
VL 20
IS 1
BP P1
EP P6
DI 10.1530/ERC-12-0351
PG 6
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA 121RZ
UT WOS:000317263200001
PM 23250906
ER
PT J
AU Dyer, KD
Percopo, CM
Rosenberg, HF
AF Dyer, Kimberly D.
Percopo, Caroline M.
Rosenberg, Helene F.
TI IL-33 promotes eosinophilia in vivo and antagonizes IL-5-dependent
eosinophil hematopoiesis ex vivo
SO IMMUNOLOGY LETTERS
LA English
DT Article
DE Eosinophil; IL-5; IL-33; GM-CSF
ID MOUSE BONE-MARROW; AIRWAY INFLAMMATION; CYTOKINE IL-33; STEM-CELLS;
RECEPTOR; ST2; MACROPHAGES; INTERLEUKIN-33; EXPANSION; LIGAND
AB IL-33 is an IL-1 family cytokine that elicits IL-5-dependent eosinophilia in vivo. We show here that IL-33 promotes minimal eosinophil hematopoiesis via direct interactions with mouse bone marrow progenitors ex vivo and that it antagonizes eosinophil hematopoiesis promoted by IL-5 on SCF and Flt3L primed bone marrow progenitor cells in culture. SCF and Flt3L primed progenitors respond to IL-33 by acquiring an adherent, macrophage-like phenotype, and by releasing macrophage-associated cytokines into the culture medium. IL-33-mediated antagonism of IL-5 was reproduced in part by the addition of GM-CSF and was inhibited by the actions of neutralizing anti-GM-CSF antibody. These findings suggest that the direct actions of IL-33 on bone marrow progenitors primed with SCF and Flt3L are antagonistic to the actions of IL-5 and are mediated in part by GM-CSF. Published by Elsevier B.V.
C1 [Dyer, Kimberly D.; Percopo, Caroline M.; Rosenberg, Helene F.] NIAID, Lab Allerg Dis, Inflammat Immunobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Dyer, KD (reprint author), 10 Ctr Dr MSC 1883,Bldg 10 Room 11C216, Bethesda, MD 20892 USA.
EM kdyer@niaid.nih.gov
FU NIAID DIR [AI000941]
FX The authors thank Dr. Paul S. Foster, University of Newcastle, New South
Wales, Australia, for providing the IL-5 gene-deleted mice on the BALB/c
background, Dr. Ricardo Dreyfuss for preparing the photomicrographs, and
Dr. Alfonso Gozalo (CMB/NIAID) and his staff at the 14BS animal facility
for care of the mice used in this work. This work is supported by NIAID
DIR funding #AI000941 to HFR.
NR 43
TC 16
Z9 16
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2478
J9 IMMUNOL LETT
JI Immunol. Lett.
PD FEB
PY 2013
VL 150
IS 1-2
BP 41
EP 47
DI 10.1016/j.imlet.2012.12.002
PG 7
WC Immunology
SC Immunology
GA 122JW
UT WOS:000317315400005
PM 23246474
ER
PT J
AU Olivera, A
Dillahunt, SE
Rivera, J
AF Olivera, Ana
Dillahunt, Sandra E.
Rivera, Juan
TI Interrogation of sphingosine-1-phosphate receptor 2 function in vivo
reveals a prominent role in the recovery from IgE and IgG-mediated
anaphylaxis with minimal effect on its onset
SO IMMUNOLOGY LETTERS
LA English
DT Article
DE Sphingosine-1-phosphate; S1PR(2); Mast cell degranulation; Anaphylaxis;
IgE; IgG
ID FC-EPSILON-RI; MAST-CELL ACTIVATION; SYSTEMIC-ANAPHYLAXIS; SPHINGOSINE
KINASE-1; FYN KINASE; ANTIBODY; MOUSE; GAMMA; DEGRANULATION;
INFLAMMATION
AB Autocrine stimulation of S1PR(2), a receptor for the lipid mediator sphingosine-1-phosphate (S1P), has been implicated in mast cell degranulation to IgE/antigen (Ag) although, paradoxically, its ligand cannot trigger substantial degranulation. Additionally, the in vivo role of S1PR(2) in the overall allergic responses is unclear since S1PR(2) was reported to be required for the onset of systemic anaphylaxis by IgE/Ag but, in apparent contradiction, also for the recovery from histamine-induced anaphylaxis in a mast cell independent manner. Here, we sought to clarify the role of S1PR(2) in mast cell degranulation and in IgE and IgG-mediated anaphylaxis. Lack of S1PR(2) reduced IgE/Ag-induced degranulation in in vitro experiments with mucosal mast cells, but had no effect on connective tissue type mast cells. This latter response correlated with a lack of involvement of S1PR(2) in the onset of non-lethal IgE/Ag-mediated systemic and cutaneous anaphylaxis. However, S1pr2(-/-) mice were slow to recover (or did not recover) from Fc epsilon RI-mediated anaphylaxis, an outcome that mirrored their known impairment in histamine clearance due to defective vascular tone. A minor role for S1PR(2) in mast cell degranulation was uncovered upon engagement of low affinity receptors for IgG and in the onset of IgG-mediated anaphylaxis. Our findings show that S1PR(2) is dispensable for initiating IgE/Ag-mediated connective tissue mast cell degranulation and anaphylaxis, but it is required for normal recovery from anaphylaxis. Published by Elsevier B.V.
C1 [Olivera, Ana; Dillahunt, Sandra E.; Rivera, Juan] NIAMSD, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA.
RP Olivera, A (reprint author), NIAMS, NIH, Bldg 10,Room 13C103, Bethesda, MD 20892 USA.
EM oliveraa@ep.niams.nih.gov; juan_rivera@nih.gov
FU Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of
Health (NIH) [AR041101-19, AR041155-06]
FX This research was supported by the Intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) of the National Institutes of Health (NIH) (Grant numbers
AR041101-19; AR041155-06). We gratefully acknowledge the contributions
of the Office of Science and Technology (Flow Cytometry and Laboratory
Animal Care and Use Sections), NIAMS.
NR 48
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Z9 10
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2478
J9 IMMUNOL LETT
JI Immunol. Lett.
PD FEB
PY 2013
VL 150
IS 1-2
BP 89
EP 96
DI 10.1016/j.imlet.2013.01.005
PG 8
WC Immunology
SC Immunology
GA 122JW
UT WOS:000317315400013
PM 23337656
ER
PT J
AU Zou, W
Izawa, T
Zhu, TT
Chappel, J
Otero, K
Monkley, SJ
Critchley, DR
Petrich, BG
Morozov, A
Ginsberg, MH
Teitelbaum, SL
AF Zou, Wei
Izawa, Takashi
Zhu, Tingting
Chappel, Jean
Otero, Karel
Monkley, Susan J.
Critchley, David R.
Petrich, Brian G.
Morozov, Alexei
Ginsberg, Mark H.
Teitelbaum, Steven L.
TI Talin1 and Rap1 Are Critical for Osteoclast Function
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID INTEGRIN ACTIVATION; C-FMS; ALPHA-V-BETA-3 INTEGRIN; BONE-RESORPTION;
BETA-3 INTEGRIN; CYTOSKELETON; SYK; DIFFERENTIATION; RECRUITMENT;
PRECURSORS
AB To determine talin1's role in osteoclasts, we mated TLN1(beta/beta) mice with those expressing cathepsin K-Cre (CtsK-TLN1) to delete the gene in mature osteoclasts or with lysozyme M-Cre (LysM-TLN1) mice to delete TLN1 in all osteoclast lineage cells. Absence of TLN1 impairs macrophage colony-stimulating factor (M-CSF)-stimulated inside-out integrin activation and cytoskeleton organization in mature osteoclasts. Talin1-deficient precursors normally express osteoclast differentiation markers when exposed to M-CSF and receptor activator of nuclear factor kappa B (RANK) ligand but attach to substrate and migrate poorly, arresting their development into mature resorptive cells. In keeping with inhibited resorption, CtsK-TLN1 mice exhibit an similar to 5-fold increase in bone mass. Osteoclast-specific deletion of Rap1 (CtsK-Rap1), which promotes talin/beta integrin recognition, yields similar osteopetrotic mice. The fact that the osteopetrosis of CtsK-TLN1 and CtsK-Rap1 mice is substantially more severe than that of those lacking alpha v beta 3 is likely due to added failed activation of beta 1 integrins. In keeping with osteoclast dysfunction, mice in whom talin is deleted late in the course of osteoclastogenesis are substantially protected from ovariectomy-induced osteoporosis and the periarticular osteolysis attending inflammatory arthritis. Thus, talin1 and Rap1 are critical for resorptive function, and their selective inhibition in mature osteoclasts retards pathological bone loss.
C1 [Zou, Wei; Izawa, Takashi; Zhu, Tingting; Chappel, Jean; Otero, Karel; Teitelbaum, Steven L.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA.
[Teitelbaum, Steven L.] Washington Univ, Sch Med, Dept Med, Div Bone & Mineral Dis, St Louis, MO 63110 USA.
[Monkley, Susan J.; Critchley, David R.] Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England.
[Petrich, Brian G.; Ginsberg, Mark H.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Morozov, Alexei] NIMH, Unit Behav Genet, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA.
RP Teitelbaum, SL (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA.
EM teitelbs@wustl.edu
OI Teitelbaum, Steven/0000-0002-4054-6679
FU National Institutes of Health [AR032788, AR046523, AR054618, AR057037,
AR057235, AR027214]
FX This work was supported by National Institutes of Health grants
AR032788, AR046523, AR054618, AR057037, and AR057235 (S.L.T.) and
AR027214 (M.H.G.).
NR 38
TC 22
Z9 24
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD FEB
PY 2013
VL 33
IS 4
BP 830
EP 844
DI 10.1128/MCB.00790-12
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 121TK
UT WOS:000317267000015
PM 23230271
ER
PT J
AU Sengupta, P
Jovanovic-Talisman, T
Lippincott-Schwartz, J
AF Sengupta, Prabuddha
Jovanovic-Talisman, Tijana
Lippincott-Schwartz, Jennifer
TI Quantifying spatial organization in point-localization superresolution
images using pair correlation analysis
SO NATURE PROTOCOLS
LA English
DT Article
ID OPTICAL RECONSTRUCTION MICROSCOPY; SINGLE-MOLECULE LOCALIZATION;
HIGH-DENSITY LOCALIZATION; FLUORESCENT-PROBES; PROTEIN HETEROGENEITY;
RESOLUTION; PALM; DYNAMICS
AB he distinctive distributions of proteins within subcellular compartments both at steady state and during signaling events have essential roles in cell function. Here we describe a method for delineating the complex arrangement of proteins within subcellular structures visualized using point-localization superresolution (PL-SR) imaging. The approach, called pair correlation photoactivated localization microscopy (PC-PALM), uses a pair-correlation algorithm to precisely identify single molecules in PL-SR imaging data sets, and it is used to decipher quantitative features of protein organization within subcellular compartments, including the existence of protein clusters and the size, density and number of proteins in these clusters. We provide a step-by-step protocol for PC-PALM, illustrating its analysis capability for four plasma membrane proteins tagged with photoactivatable GFP (PAGFP). The experimental steps for PC-PALM can be carried out in 3 d and the analysis can be done in similar to 6-8 h. Researchers need to have substantial experience in single-molecule imaging and statistical analysis to conduct the experiments and carry out this analysis.
C1 [Sengupta, Prabuddha; Jovanovic-Talisman, Tijana; Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Lippincott-Schwartz, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
EM jlippin@helix.nih.gov
OI Sengupta, Prabuddha/0000-0001-7094-6967; Jovanovic-Talisman,
Tijana/0000-0003-1928-4763
FU Intramural NIH HHS [Z99 HD999999]
NR 40
TC 40
Z9 40
U1 6
U2 50
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
J9 NAT PROTOC
JI Nat. Protoc.
PD FEB
PY 2013
VL 8
IS 2
BP 345
EP 354
DI 10.1038/nprot.2013.005
PG 10
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 119PN
UT WOS:000317109900008
PM 23348362
ER
PT J
AU Reis, JP
Loria, CM
Launer, LJ
Sidney, S
Liu, K
Jacobs, DR
Zhu, N
Lloyd-Jones, DM
He, K
Yaffe, K
AF Reis, Jared P.
Loria, Catherine M.
Launer, Lenore J.
Sidney, Stephen
Liu, Kiang
Jacobs, David R., Jr.
Zhu, Na
Lloyd-Jones, Donald M.
He, Ka
Yaffe, Kristine
TI Cardiovascular health through young adulthood and cognitive functioning
in midlife
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID RISK-FACTORS; METABOLIC SYNDROME; INCIDENT DEMENTIA; BLOOD-PRESSURE; US
ADULTS; IMPAIRMENT; LIFE; DECLINE; CARDIA; ASSOCIATION
AB Objective A study was undertaken to examine the association between overall cardiovascular health as recently defined by the American Heart Association in young adulthood to middle age and cognitive function in midlife. Overall ideal cardiovascular health incorporates 7 metrics, including the avoidance of overweight or obesity, a healthful diet, nonsmoking, and physical activity, total cholesterol, blood pressure, and fasting glucose at goal levels. Methods This analysis of the Coronary Artery Risk Development in Young Adults study, a multicenter community-based study with 25 years of follow-up, included 2,932 participants aged 18 to 30 years at baseline (year 0) who attended follow-up examinations at years 7 and 25. Cardiovascular health metrics were measured at each examination. The Digit Symbol Substitution Test (DSST), modified Stroop test, and Rey Auditory Verbal Learning Test (RAVLT) were completed at year 25. Results A greater number of ideal cardiovascular metrics in young adulthood and middle age were independently associated with better cognitive function in midlife (p for trend < 0.01, for all). Specifically, each additional ideal metric was associated with 1.32 more symbols on the DSST (95% confidence interval [CI] = 0.93 1.71), a 0.77-point lower interference score on the Stroop test (95% CI=1.03 to 0.45), and 0.12 more words on the RAVLT (95% CI = 0.04 to 0.20). Participants who had 5 ideal metrics at a greater number of the 3 examinations over the 25-year period exhibited better performance on each cognitive test in middle age (p for trend < 0.01, for all). Interpretation Ideal cardiovascular health in young adulthood and its maintenance to middle age is associated with better psychomotor speed, executive function, and verbal memory in midlife. ANN NEUROL 2013;73:170179
C1 [Reis, Jared P.; Loria, Catherine M.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Sidney, Stephen] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA.
[Liu, Kiang; Lloyd-Jones, Donald M.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Jacobs, David R., Jr.; Zhu, Na] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Jacobs, David R., Jr.] Univ Oslo, Dept Nutr, Oslo, Norway.
[He, Ka] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[He, Ka] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Reis, JP (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Suite 10197, Bethesda, MD 20892 USA.
EM reisjp@mail.nih.gov
FU National Heart, Lung, and Blood Institute; University of Alabama at
Birmingham [N01-HC95095, N01-HC48047]; Kaiser Foundation Research
Institute [N01-HC48050]; Northwestern University [N01-HC48049];
University of Minnesota [N01-HC48048]
FX CARDIA is conducted and supported by the National Heart, Lung, and Blood
Institute in collaboration with the University of Alabama at Birmingham
(N01-HC95095, N01-HC48047), Kaiser Foundation Research Institute
(N01-HC48050), Northwestern University (N01-HC48049), and University of
Minnesota (N01-HC48048).
NR 38
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Z9 41
U1 0
U2 18
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD FEB
PY 2013
VL 73
IS 2
BP 170
EP 179
DI 10.1002/ana.23836
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 113UA
UT WOS:000316693200006
PM 23443990
ER
PT J
AU Fitzgerald, KC
O'Reilly, EJ
Fondell, E
Falcone, GJ
McCullough, ML
Park, Y
Kolonel, LN
Ascherio, A
AF Fitzgerald, Kathryn C.
O'Reilly, Eilis J.
Fondell, Elinor
Falcone, Guido J.
McCullough, Marjorie L.
Park, Yikyung
Kolonel, Laurence N.
Ascherio, Alberto
TI Intakes of vitamin C and carotenoids and risk of amyotrophic lateral
sclerosis: Pooled results from 5 cohort studies
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID FOOD-FREQUENCY QUESTIONNAIRE; HEALTH-AMERICAN-ASSOCIATION; SOCIETY
CANCER PREVENTION; BASE-LINE CHARACTERISTICS; RETIRED-PERSONS DIET;
MOTOR-NEURON DISEASE; NATIONAL-INSTITUTES; OXIDATIVE STRESS; SURVIVAL;
WOMEN
AB Objective Prior research has suggested the possible role of oxidative stress in the pathogenesis of amyotrophic lateral sclerosis (ALS). Prospective data examining dietary antioxidants such carotenoids and vitamin C are limited. Methods Risk of ALS associated with carotenoid and vitamin C intake was investigated in 5 prospective cohorts: the National Institutes of HealthAssociation of American Retired Persons Diet and Health Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort, the Health Professionals Follow-up Study (HPFS), and the Nurses Health Study (NHS). ALS deaths were documented using the National Death Index, and confirmed nonfatal ALS cases were included from HPFS and NHS. A total of 1,153 ALS deaths occurred among 1,100,910 participants (562,942 men; 537,968 women). Participants were categorized into cohort-specific quintiles of intake for dietary variables. We applied Cox proportional hazards regression to calculate cohort-specific risk ratios (RRs), and pooled results using random-effects methods. Results A greater total major carotenoids intake was associated with a reduced risk of ALS (pooled, multivariate-adjusted RR for the highest to the lowest quintile = 0.75, 95% confidence interval [CI] = 0.610.91, p for trend = 0.004). Individually, higher dietary intakes of -carotene and lutein were inversely associated with ALS risk. The pooled multivariate RRs comparing the highest to the lowest quintile for -carotene and lutein were 0.85 (95% CI = 0.641.13, p for trend = 0.03) and 0.79 (95% CI = 0.640.96, p for trend = 0.01), respectively. Lycopene, -cryptoxanthin, and vitamin C were not associated with reduced risk of ALS. Interpretation Consumption of foods high in carotenoids may help prevent or delay onset of ALS. ANN NEUROL 2013;73:236245
C1 [Fitzgerald, Kathryn C.; O'Reilly, Eilis J.; Fondell, Elinor; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[O'Reilly, Eilis J.; Ascherio, Alberto] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[O'Reilly, Eilis J.; Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA USA.
[Falcone, Guido J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Falcone, Guido J.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[McCullough, Marjorie L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Kolonel, Laurence N.] Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96822 USA.
RP Fitzgerald, KC (reprint author), 665 Huntington Ave, Boston, MA 02115 USA.
EM hpkcf@channing.harvard.edu
RI Falcone, Guido/L-2287-2016;
OI Falcone, Guido/0000-0002-6407-0302; Park, Yikyung/0000-0002-6281-489X
FU NIH/National Institute of Neurological Diseases and Stroke [R01
NS045893]; NIH/NCI [R37 CA54281]; neurological diseases and stroke (NIH)
[P01 CA87969]; NIH [P01 CA055075]; Blanceflor Foundation (Stockholm,
Sweden); Michael J Fox Foundation; Accelerated Cure Project; F.
Hoffmann-La Roche; Merck Serono
FX This work was supported by grant R01 NS045893 from the NIH/National
Institute of Neurological Diseases and Stroke. The multiethnic cohort
study was supported by NIH/NCI R37 CA54281. Nurses Health Study is
funded by neurological diseases and stroke (NIH) program project P01
CA87969 and Health Professional Follow-up Study by NIH program project
P01 CA055075. E.F. received a postdoctoral scholarship from the
Blanceflor Foundation (Stockholm, Sweden).; K.C.F.: grants/grants
pending, NIH. E.J.O.: grants/grants pending, NIH. A.A.: grants/grants
pending, National Institutes of Health, Michael J Fox Foundation,
Accelerated Cure Project; speaking fees, F. Hoffmann-La Roche, Merck
Serono.
NR 39
TC 19
Z9 21
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD FEB
PY 2013
VL 73
IS 2
BP 236
EP 245
DI 10.1002/ana.23820
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 113UA
UT WOS:000316693200012
PM 23362045
ER
PT J
AU Donsante, A
Sullivan, P
Goldstein, DS
Brinster, LR
Kaler, SG
AF Donsante, Anthony
Sullivan, Patricia
Goldstein, David S.
Brinster, Lauren R.
Kaler, Stephen G.
TI L-Threo-Dihydroxyphenylserine corrects neurochemical abnormalities in a
menkes disease mouse model
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID DOPAMINE-BETA-HYDROXYLASE; COPPER TRANSPORT; NEONATAL DIAGNOSIS;
METABOLIC STRESS; ATP7A MUTATION; PC12 CELLS;
3,4-DIHYDROXYPHENYLACETALDEHYDE; NORADRENALINE; DEFICIENCY;
3,4-DIHYDROXYPHENYLGLYCOLALDEHYDE
AB Objective Menkes disease is a lethal neurodegenerative disorder of infancy caused by mutations in a copper-transporting adenosine triphosphatase gene, ATP7A. Among its multiple cellular tasks, ATP7A transfers copper to dopamine beta hydroxylase (DBH) within the lumen of the Golgi network or secretory granules, catalyzing the conversion of dopamine to norepinephrine. In a well-established mouse model of Menkes disease, mottled-brindled (mo-br), we tested whether systemic administration of L-threo-dihydroxyphenylserine (L-DOPS), a drug used successfully to treat autosomal recessive norepinephrine deficiency, would improve brain neurochemical abnormalities and neuropathology. Methods At 8, 10, and 12 days of age, wild-type and mo-br mice received intraperitoneal injections of 200g/g body weight of L-DOPS, or mock solution. Five hours after the final injection, the mice were euthanized, and brains were removed. We measured catecholamine metabolites affected by DBH via high-performance liquid chromatography with electrochemical detection, and assessed brain histopathology. Results Compared to mock-treated controls, mo-br mice that received intraperitoneal L-DOPS showed significant increases in brain norepinephrine (p < 0.001) and its deaminated metabolite, dihydroxyphenylglycol (p < 0.05). The ratio of a nonbeta-hydroxylated metabolite in the catecholamine biosynthetic pathway, dihydroxyphenylacetic acid, to the beta-hydroxylated metabolite, dihydroxyphenylglycol, improved equivalently to results obtained previously with brain-directed ATP7A gene therapy (p < 0.01). However, L-DOPS treatment did not arrest global brain pathology or improve somatic growth, as gene therapy had. Interpretation We conclude that (1) L-DOPS crosses the bloodbrain barrier in mo-br mice and corrects brain neurochemical abnormalities, (2) norepinephrine deficiency is not the cause of neurodegeneration in mo-br mice, and (3) L-DOPS treatment may ameliorate noradrenergic hypofunction in Menkes disease. ANN NEUROL 2013;73:259265
C1 [Donsante, Anthony; Kaler, Stephen G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, Rockville, MD USA.
[Sullivan, Patricia; Goldstein, David S.] NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA.
[Brinster, Lauren R.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA.
RP Kaler, SG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, NIH, Bldg 10,Room 10N313,10 Ctr Dr MSC 1853, Bethesda, MD 20892 USA.
EM kalers@mail.nih.gov
FU National Institute of Child Health and Human Development; National
Institute of Neurological Disorders and Stroke
FX This work was supported by the intramural research programs of the
National Institute of Child Health and Human Development and National
Institute of Neurological Disorders and Stroke.
NR 27
TC 8
Z9 8
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD FEB
PY 2013
VL 73
IS 2
BP 259
EP 265
DI 10.1002/ana.23787
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 113UA
UT WOS:000316693200014
PM 23224983
ER
PT J
AU Bonucci, A
Balducci, E
Pistolesi, S
Pogni, R
AF Bonucci, Alessio
Balducci, Enrico
Pistolesi, Sara
Pogni, Rebecca
TI The defensin-lipid interaction: Insights on the binding states of the
human antimicrobial peptide HNP-1 to model bacterial membranes
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
LA English
DT Article
DE HNP-1; Antimicrobial peptide; Bacterial model membrane; Bilayer
interaction; Spectroscopic analysis; Partition coefficient
ID PORE FORMATION; TRYPTOPHAN FLUORESCENCE; COMBINATORIAL DESIGN;
INTERFACIAL ACTIVITY; MECHANISM; PHOSPHOLIPIDS; ANTIBIOTICS; INSERTION;
MODULATE; BILAYERS
AB Antimicrobial peptides are an important component of innate immunity and have generated considerable interest as a new potential class of natural antibiotics. The biological activity of antimicrobial peptides is strongly influenced by peptide membrane interactions. Human Neutrophil Peptide 1 (HNP-1) is a 30 aminoacid peptide, belonging to the class of alpha-defensins. Many biophysical studies have been performed on this peptide to define its mechanism of action. Combining spectroscopic and thermodynamic analysis, insights on the interaction of the alpha-defensin with POPE:POPG:CL negative charged bilayers are given. The binding states of the peptide below and above the threshold concentration have been analyzed showing that the interaction with lipid bilayers is dependent by peptide concentration. These novel results that indicate how affinity and biological activities of natural antibiotics are depending by their concentration, might open new way of investigation of the antimicrobial mode of action. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Bonucci, Alessio; Pogni, Rebecca] Univ Siena, Dept Chem, I-53100 Siena, Italy.
[Balducci, Enrico] Univ Camerino, Sch Biosci & Biotechnol, I-62032 Camerino, Italy.
[Pistolesi, Sara] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Pogni, R (reprint author), Univ Siena, Dept Chem, Via A de Gasperi 2, I-53100 Siena, Italy.
EM rebecca.pogni@unisi.it
NR 49
TC 9
Z9 9
U1 1
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2736
J9 BBA-BIOMEMBRANES
JI Biochim. Biophys. Acta-Biomembr.
PD FEB
PY 2013
VL 1828
IS 2
BP 758
EP 764
DI 10.1016/j.bbamem.2012.11.011
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 090UD
UT WOS:000315004600065
PM 23159481
ER
PT J
AU Mathe, D
Horvath, I
Szigeti, K
Donohue, SR
Pike, VW
Jia, ZS
Ledent, C
Palkovits, M
Freund, TF
Halldin, C
Gulyas, B
AF Mathe, Domokos
Horvath, Ildiko
Szigeti, Krisztian
Donohue, Sean R.
Pike, Victor W.
Jia, Zisheng
Ledent, Catherine
Palkovits, Miklos
Freund, Tamas F.
Halldin, Christer
Gulyas, Balazs
TI In vivo SPECT and ex vivo autoradiographic brain imaging of the novel
selective CB1 receptor antagonist radioligand [I-125]SD7015 in CB1
knock-out and wildtype mouse
SO BRAIN RESEARCH BULLETIN
LA English
DT Article
DE Endocannabinoid CB1 receptor (CB1R); Single photon emission computed
tomography (SPECT); Molecular imaging biomarker; [I-125]SD7015;
Knock-out CB1R-/- mouse; Multiplexed multipinhole dedicated small animal
SPECT/CT system
ID POSITRON-EMISSION-TOMOGRAPHY; SITU HYBRIDIZATION HISTOCHEMISTRY; TYPE-1
CANNABINOID RECEPTOR; MESSENGER-RNA EXPRESSION; RAT-BRAIN;
PARKINSONS-DISEASE; ENDOCANNABINOID SYSTEM; NERVOUS-SYSTEM; ENDOGENOUS
CANNABINOIDS; COMPUTED-TOMOGRAPHY
AB We aimed to evaluate the novel high-affinity and relatively lipophilic CB1 receptor (CB1R) antagonist radioligand [I-125]SD7015 for SPECT imaging of CB(1)Rs in vivo using the multiplexed multipinhole dedicated small animal SPECT/CT system, NanoSPECT/CTPLUS (Mediso, Budapest, Hungary), in knock-out CB1 receptor knock-out (CB1R-/-) and wildtype mice. In order to exclude possible differences in cerebral blood flow between the two types of animals, HMPAO SPECT scans were performed, whereas in order to confirm the brain uptake differences of the radioligand between knock-out mice and wildtype mice, in vivo scans were complemented with ex vivo autoradiographic measurements using the brains of the same animals. With SPECT/CT imaging, we measured the brain uptake of radioactivity, using %SUV (% standardised uptake values) in CB1R-/- mice (n = 3) and C57BL6 wildtype mice (n = 7) under urethane anaesthesia after injecting [I-125]SD7015 intravenously or intraperitoneally. The Brookhaven Laboratory mouse MRI atlas was fused to the SPECT/CT images by using a combination of rigid and non-rigid algorithms in the Mediso FuSiori (TM) (Mediso, Budapest, Hungary) and VivoQuant (inviCRO, Boston, MA, USA) softwares. Phosphor imager plate autoradiography (ARG) was performed on 4 mu m-thin cryostat sections of the excised brains. %SUV was 8.6 +/- 3.6 (average +/- SD) in (CBR)-R-1-/- mice and 22.1 +/- 12.4 in wildtype mice between 2 and 4 h after injection (p < 0.05). ARG of identically taken sections from wildtype mouse brain showed moderate radioactivity uptake when compared with the in vivo images, with a clear difference between grey matter and white matter, whereas ARG in CB1R(-/-) mice showed practically no radioactivity uptake. [I-125]SD7015 enters the mouse brain in sufficient amount to enable SPECT imaging. Brain radioactivity distribution largely coincides with that of the known CB1R expression pattern in rodent brain. We conclude that [I-125]SD7015 should be a useful SPECT radioligand for studying brain CB1R in mouse and rat disease models. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Mathe, Domokos; Horvath, Ildiko; Szigeti, Krisztian] Semmelweis Univ, Dept Biophys & Radiat Biol, H-1094 Budapest, Hungary.
[Mathe, Domokos; Szigeti, Krisztian] CROmed Translat Res Ctr, H-1047 Budapest, Hungary.
[Donohue, Sean R.; Pike, Victor W.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Jia, Zisheng; Halldin, Christer; Gulyas, Balazs] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden.
[Ledent, Catherine] Univ Libre Brussels, IRIBHM, B-1070 Brussels, Belgium.
[Palkovits, Miklos] Semmelweis Univ, Dept Anat, Neuromorphol Lab, H-1094 Budapest, Hungary.
[Freund, Tamas F.] Hungarian Acad Sci, Inst Expt Med, H-1083 Budapest, Hungary.
RP Gulyas, B (reprint author), Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden.
EM balazs.gulyas@ki.se
RI Palkovits, Miklos/F-2707-2013; Gulyas, Balazs/F-9508-2015;
OI Palkovits, Miklos/0000-0003-0578-0387
FU EU FP7 INMIND Project (Imaging of Neuroinflammation in Neurodegenerative
Diseases)
FX The study was performed partly within a collaborative master research
agreement between Karolinska Institutet, Mediso Medical Imaging Systems
and CROmed Translational. This study was partially supported by the EU
FP7 INMIND Project (Imaging of Neuroinflammation in Neurodegenerative
Diseases).
NR 60
TC 0
Z9 0
U1 0
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0361-9230
J9 BRAIN RES BULL
JI Brain Res. Bull.
PD FEB
PY 2013
VL 91
BP 46
EP 51
DI 10.1016/j.brainresbull.2013.01.001
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 115UA
UT WOS:000316836200007
PM 23318272
ER
PT J
AU Yang, MJ
Li, XL
Turkbey, B
Choyke, PL
Yan, PK
AF Yang, Meijuan
Li, Xuelong
Turkbey, Baris
Choyke, Peter L.
Yan, Pingkun
TI Prostate Segmentation in MR Images Using Discriminant Boundary Features
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Discriminant analysis; image feature; prostate segmentation; statistical
shape model (SSM)
ID ACTIVE SHAPE MODEL; CT IMAGES; APPEARANCE
AB Segmentation of the prostate in magnetic resonance image has become more in need for its assistance to diagnosis and surgical planning of prostate carcinoma. Due to the natural variability of anatomical structures, statistical shape model has been widely applied in medical image segmentation. Robust and distinctive local features are critical for statistical shape model to achieve accurate segmentation results. The scale invariant feature transformation (SIFT) has been employed to capture the information of the local patch surrounding the boundary. However, when SIFT feature being used for segmentation, the scale and variance are not specified with the location of the point of interest. To deal with it, the discriminant analysis in machine learning is introduced to measure the distinctiveness of the learned SIFT features for each landmark directly and to make the scale and variance adaptive to the locations. As the gray values and gradients vary significantly over the boundary of the prostate, separate appearance descriptors are built for each landmark and then optimized. After that, a two stage coarse-to-fine segmentation approach is carried out by incorporating the local shape variations. Finally, the experiments on prostate segmentation from MR image are conducted to verify the efficiency of the proposed algorithms.
C1 [Yang, Meijuan; Li, Xuelong; Yan, Pingkun] Chinese Acad Sci, Ctr OPT IMagery Anal & Learning, State Key Lab Transient Opt & Photon, Xian Inst Opt & Precis Mech, Xian 710119, Shaanxi, Peoples R China.
[Turkbey, Baris; Choyke, Peter L.] NCI, NIH, Bethesda, MD 20892 USA.
RP Yan, PK (reprint author), Chinese Acad Sci, Ctr OPT IMagery Anal & Learning, State Key Lab Transient Opt & Photon, Xian Inst Opt & Precis Mech, Xian 710119, Shaanxi, Peoples R China.
EM meijuan.yang@opt.ac.cn; xuelong-li@opt.ac.cn; turkbeyi@mail.nih.gov;
pchoyke@mail.nih.gov; pingkun@ieee.org
FU National Basic Research Program of China (973 Program) [2012CB719905];
National Natural Science Foundation of China [61105012, 61172142]; Open
Project Program of the State Key Lab of CAD&CG, Zhejiang University
[A1116]
FX This work was supported in part by the National Basic Research Program
of China (973 Program) under Grant 2012CB719905, the National Natural
Science Foundation of China under Grant 61105012 and Grant 61172142, and
the Open Project Program of the State Key Lab of CAD&CG under Grant
A1116, Zhejiang University. Asterisk indicates corresponding author.
NR 21
TC 9
Z9 9
U1 0
U2 9
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD FEB
PY 2013
VL 60
IS 2
BP 479
EP 488
DI 10.1109/TBME.2012.2228644
PG 10
WC Engineering, Biomedical
SC Engineering
GA 115KA
UT WOS:000316809800024
PM 23192474
ER
PT J
AU Morens, DM
AF Morens, David M.
TI Commentary: Cholera conundrums and proto-epidemiologic puzzles. The
confusing epidemic world of John Lea and John Snow
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
C1 NIAID, Off Director, NIH, Bethesda, MD 20892 USA.
RP Morens, DM (reprint author), NIAID, Off Director, NIH, Bldg 31,Room 7A-03,31 Ctr Dr, Bethesda, MD 20892 USA.
EM dm270q@nih.gov
NR 64
TC 2
Z9 2
U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD FEB
PY 2013
VL 42
IS 1
BP 43
EP 52
DI 10.1093/ije/dyt016
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 113WE
UT WOS:000316699300004
PM 23508406
ER
PT J
AU Shi, M
Umbach, DM
Weinberg, CR
AF Shi, Min
Umbach, David M.
Weinberg, Clarice R.
TI Case-sibling studies that acknowledge unstudied parents and permit the
inclusion of unmatched individuals
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Genetic association; case-sibling; missing parents;
expectation-maximization algorithm; conditional logistic regression
ID GENE-ENVIRONMENT INTERACTION; MISSING GENOTYPE DATA; FAMILY-BASED TESTS;
LINKAGE DISEQUILIBRIUM; ASSOCIATION ANALYSIS; UNRELATED SUBJECTS;
INCOMPLETE DATA; TRIADS; POWER; LIKELIHOOD
AB Background Family-based designs enable assessment of genetic associations without bias from population stratification. When parents are not readily available - especially for diseases with onset later in life - the case-sibling design, where each case is matched with one or more unaffected siblings, is useful. Analysis typically accounts for within-family dependencies by using conditional logistic regression (CLR).
Methods We consider an alternative to CLR that treats each case-sibling set as a nuclear family with both parents missing by design. One can carry out maximum likelihood analysis by using the Expectation-Maximization (EM) algorithm to account for missing parental genotypes. We compare conditional logistic regression and the missing-parents approach under several risk scenarios.
Results We show that the missing-parents approach improves power when some families have more than one unaffected sibling and that under weak assumptions the approach permits the incorporation of supplemental cases who have no sibling available and supplemental controls whose case sibling is unavailable (e.g., due to disability or death).
Conclusion The missing-parents approach offers both improved statistical efficiency and asymptotically unbiased estimation for genotype relative risks and genotype-by-exposure interaction parameters.
C1 [Shi, Min; Umbach, David M.; Weinberg, Clarice R.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC USA.
RP Shi, M (reprint author), NIEHS, Biostat Branch, A3-03 101-A352, Res Triangle Pk, NC 27709 USA.
EM shi2@niehs.nih.gov
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [Z01 ES040007, Z01 ES045002]
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences, under project
numbers Z01 ES040007 and Z01 ES045002.
NR 31
TC 2
Z9 2
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD FEB
PY 2013
VL 42
IS 1
BP 298
EP 307
DI 10.1093/ije/dys212
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 113WE
UT WOS:000316699300037
PM 23248214
ER
PT J
AU De Matteis, S
Consonni, D
Lubin, JH
Tucker, M
Peters, S
Vermeulen, RCH
Kromhout, H
Bertazzi, PA
Caporaso, NE
Pesatori, AC
Wacholder, S
Landi, MT
AF De Matteis, Sara
Consonni, Dario
Lubin, Jay H.
Tucker, Margaret
Peters, Susan
Vermeulen, Roel C. H.
Kromhout, Hans
Bertazzi, Pier Alberto
Caporaso, Neil E.
Pesatori, Angela C.
Wacholder, Sholom
Landi, Maria Teresa
TI Authors' response to: Qualitative job-exposure matrix-a tool for the
quantification of population-attributable fractions for occupational
lung carcinogens?
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Letter
ID CANCER RISK; EXPERT
C1 [De Matteis, Sara; Consonni, Dario; Bertazzi, Pier Alberto; Pesatori, Angela C.] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Epidemiol Unit, Dept Prevent Med, Milan, Italy.
[De Matteis, Sara; Consonni, Dario; Bertazzi, Pier Alberto; Pesatori, Angela C.] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
[De Matteis, Sara; Lubin, Jay H.; Tucker, Margaret; Caporaso, Neil E.; Wacholder, Sholom; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Peters, Susan; Vermeulen, Roel C. H.; Kromhout, Hans] Univ Utrecht, Inst Risk Assessment Sci, Environm Epidemiol Div, Utrecht, Netherlands.
[Peters, Susan] Univ Western Australia, Western Australian Inst Med Res, Nedlands, WA 6009, Australia.
RP Landi, MT (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM landim@mail.nih.gov
RI Peters, Susan/A-5845-2013; Tucker, Margaret/B-4297-2015; Consonni,
Dario/K-7943-2016; Vermeulen, Roel/F-8037-2011; bertazzi, pietro
alberto/D-5039-2017;
OI Consonni, Dario/0000-0002-8935-3843; Vermeulen,
Roel/0000-0003-4082-8163; bertazzi, pietro alberto/0000-0003-3475-2449;
Peters, Susan/0000-0001-5662-1971; pesatori, angela/0000-0002-0261-3252
NR 14
TC 0
Z9 0
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD FEB
PY 2013
VL 42
IS 1
BP 357
EP 358
DI 10.1093/ije/dys193
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 113WE
UT WOS:000316699300044
PM 23266616
ER
PT J
AU Yeung, EH
Zhang, C
Albert, PS
Mumford, SL
Ye, A
Perkins, NJ
Wactawski-Wende, J
Schisterman, EF
AF Yeung, E. H.
Zhang, C.
Albert, P. S.
Mumford, S. L.
Ye, A.
Perkins, N. J.
Wactawski-Wende, J.
Schisterman, E. F.
TI Adiposity and sex hormones across the menstrual cycle: the BioCycle
Study
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
DE adiposity; body mass index; body composition; sex hormones; menstrual
cycle; estradiol
ID EARLY MENOPAUSAL TRANSITION; PREMENOPAUSAL WOMEN; BODY-SIZE;
REPRODUCTIVE HORMONES; OBESE WOMEN; WEIGHT; GONADOTROPIN; ETHNICITY;
LEPTIN; FAT
AB OBJECTIVE: To investigate the influence of adiposity on patterns of sex hormones across the menstrual cycle among regularly menstruating women.
SUBJECTS: The BioCycle Study followed 239 healthy women for 1-2 menstrual cycles, with up to eight visits per cycle timed using fertility monitors.
METHODS: Serum estradiol (E2), progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) were measured at each visit. Adiposity was measured by anthropometry and by dual energy X-ray absorptiometry (DXA). Differences in hormonal patterns by adiposity measures were estimated using nonlinear mixed models, which allow for comparisons in overall mean levels, amplitude (i.e., lowest to highest level within each cycle) and shifts in timing of peaks while adjusting for age, race, energy intake and physical activity.
RESULTS: Compared with normal weight women (n = 154), obese women (body mass index (BMI) >= 30 kgm(-2), n = 25) averaged lower levels of progesterone (-15%, P = 0.003), LH (-17%, P = 0.01), FSH (-23%, P = 0.001) and higher free E2 (+22%, P = 0.0001) across the cycle. To lesser magnitudes, overweight women (BMI: 25-30, n = 60) also exhibited differences in the same directions for mean levels of free E2, FSH and LH. Obese women experienced greater changes in amplitude of LH (9%, P = 0.002) and FSH (8%, P = 0.004), but no differences were observed among overweight women. Higher central adiposity by top compared to bottom tertile of trunk-to-leg fat ratio by DXA was associated with lower total E2 (-14%, P = 0.005), and FSH (-15%, P = 0.001). Peaks in FSH and LH occurred later (similar to 0.5 day) in the cycle among women with greater central adiposity.
CONCLUSION: Greater total and central adiposity were associated with changes in mean hormone levels. The greater amplitudes observed among obese women suggest compensatory mechanisms at work to maintain hormonal homeostasis. Central adiposity may be more important in influencing timing of hormonal peaks than total adiposity. International Journal of Obesity (2013) 37, 237-243; doi:10.1038/ijo.2012.9; published online 7 February 2012
C1 [Yeung, E. H.; Zhang, C.; Albert, P. S.; Mumford, S. L.; Ye, A.; Perkins, N. J.; Schisterman, E. F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
[Wactawski-Wende, J.] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14260 USA.
[Wactawski-Wende, J.] SUNY Buffalo, Sch Med, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
RP Yeung, EH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,7B03, Bethesda, MD 20892 USA.
EM yeungedw@mail.nih.gov
RI Yeung, Edwina/F-5992-2015;
OI Yeung, Edwina/0000-0002-3851-2613; Perkins, Neil/0000-0002-6802-4733;
Schisterman, Enrique/0000-0003-3757-641X
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health & Human Development, National Institutes of
Health
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health & Human Development,
National Institutes of Health. We thank the BioCycle working group for
comments and feedback on this work.
NR 28
TC 11
Z9 12
U1 1
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0307-0565
J9 INT J OBESITY
JI Int. J. Obes.
PD FEB
PY 2013
VL 37
IS 2
BP 237
EP 243
DI 10.1038/ijo.2012.9
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 117DK
UT WOS:000316932100013
PM 22310471
ER
PT J
AU Dorn, JD
Ahuja, AK
Caspi, A
da Cruz, L
Dagnelie, G
Sahel, JA
Greenberg, RJ
McMahon, MJ
AF Dorn, Jessy D.
Ahuja, Ashish K.
Caspi, Avi
da Cruz, Lyndon
Dagnelie, Gislin
Sahel, Jose-Alain
Greenberg, Robert J.
McMahon, Matthew J.
CA Argus II Study Grp
TI The Detection of Motion by Blind Subjects With the Epiretinal
60-Electrode (Argus II) Retinal Prosthesis
SO JAMA OPHTHALMOLOGY
LA English
DT Article
ID RETINITIS-PIGMENTOSA; VISUAL PROSTHESIS; PHOTORECEPTORS; IMPLANTATION;
FEASIBILITY; PERCEPTION; TRIAL
AB Objective: To investigate the ability of 28 blind subjects implanted with a 60-electrode Argus II (Second Sight Medical Products Inc) retinal prosthesis system to detect the direction of a moving object.
Methods: Blind subjects (bare light perception or worse in both eyes) with retinitis pigmentosa were implanted with the Argus II prosthesis as part of a phase 1/2 feasibility study at multiple clinical sites worldwide. The experiment measured their ability to detect the direction of motion of a high-contrast moving bar on a flatscreen monitor in 3 conditions: with the prosthesis system on and a 1-to-1 mapping of spatial information, with the system off, and with the system on but with randomly scrambled spatial information.
Results: Fifteen subjects (54%) were able to perform the task significantly better with their prosthesis system than they were with their residual vision, 2 subjects had significantly better performance with their residual vision, and no difference was found for 11 subjects. Of the 15 better-performing subjects, 11 were available for follow-up testing, and 10 of them had significantly better performance with normal rather than with scrambled spatial information.
Conclusions: This work demonstrates that blind subjects implanted with the Argus II retinal prosthesis were able to perform a motion detection task they could not do with their native vision, confirming that electrical stimulation of the retina provides spatial information from synchronized activation of multiple electrodes.
C1 [Dorn, Jessy D.; Caspi, Avi; Greenberg, Robert J.] Second Sight Med Prod, Sylmar, CA 91342 USA.
[Ahuja, Ashish K.] Univ So Calif, Los Angeles, CA USA.
[da Cruz, Lyndon] Moorfields Eye Hosp, London, England.
[Sahel, Jose-Alain] UCL, Inst Ophthalmol, London, England.
[Dagnelie, Gislin] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[McMahon, Matthew J.] NEI, Bethesda, MD 20892 USA.
[Sahel, Jose-Alain] Univ Paris 06, Dept Therapeut, Inst Vis, UMR S 968, Paris, France.
[Sahel, Jose-Alain] CNRS, UMR 7210, Paris, France.
[Sahel, Jose-Alain] Ctr Hosp Natl Ophtalmol Quinze Vingts, Clin Invest Ctr 503, Paris, France.
RP Dorn, JD (reprint author), Second Sight Med Prod, 12744 San Fernando Rd,Bldg 3, Sylmar, CA 91342 USA.
EM jdorn@2-sight.com
RI Sahel, Jose-Alain/F-3172-2017
FU National Institutes of Health (National Eye Institute's
Research/Development of Artificial Retinas for the Blind) [EY012893]
FX This study was funded by grant EY012893 from the National Institutes of
Health (National Eye Institute's Research/Development of Artificial
Retinas for the Blind) to Dr Greenberg (principal investigator).
NR 13
TC 41
Z9 43
U1 0
U2 31
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6165
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD FEB
PY 2013
VL 131
IS 2
BP 183
EP 189
DI 10.1001/2013.jamaophthalmol.221
PG 7
WC Ophthalmology
SC Ophthalmology
GA 113RB
UT WOS:000316684400008
PM 23544203
ER
PT J
AU Merikangas, KR
He, JP
Rapoport, J
Vitiello, B
Olfson, M
AF Merikangas, Kathleen R.
He, Jian-ping
Rapoport, Judith
Vitiello, Benedetto
Olfson, Mark
TI Medication Use in US Youth With Mental Disorders
SO JAMA PEDIATRICS
LA English
DT Article
ID SUPPLEMENT NCS-A; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER;
2ND-GENERATION ANTIPSYCHOTIC MEDICATIONS; RANDOMIZED CONTROLLED-TRIAL;
ATYPICAL ANTIPSYCHOTICS; ADOLESCENT DEPRESSION; BIPOLAR DISORDER;
NATIONAL TRENDS; PSYCHOPHARMACOLOGICAL TREATMENT; PSYCHOTROPIC
MEDICATIONS
AB Objective: To evaluate the prevalence, demographic and clinical correlates, and specificity of classes of psychotropic medications indicated for mental disorders.
Design: Cross-sectional survey.
Setting: Direct household interviews of combined household and school samples representative of the general population of adolescents in the United States.
Participants: Ten thousand one hundred twenty-three adolescents aged 13 to 18 years who participated in the National Comorbidity Survey Adolescent Supplement.
Main Exposures: Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) mental disorders and neurodevelopmental disorders.
Outcome Measure: Psychotropic medication use in the past 12 months.
Results: Among youth with any DSM-IV mental disorder, 14.2% reported that they had been treated with a psychotropic medication in the past 12 months. Strong associations emerged between specific disorders and classes of medications with evidence for efficacy. Antidepressants were most frequently used among those with primary mood disorders (14.1%); stimulant use was most common among those with attention-deficit/hyperactivity disorder (20.4%); and antipsychotic use was infrequent and mostly seen among those with serious developmental disorders. Less than 2.5% of adolescents without a 12-month mental disorder had been prescribed psychotropic medications, and most had evidence of psychological distress or impairment reflected in a previous mental disorder, subthreshold condition, or developmental disorder. Appropriate medication use was significantly more frequent among those in treatment in the mental health specialty sector than general medicine or other settings.
Conclusions: These findings challenge recent concerns over widespread overmedication and misuse of psychotropic medications in US youth. In fact, these data highlight the need for greater recognition and appropriate treatment of youth with mental health disorders. JAMA Pediatr. 2013; 167(2): 141-148. Published online December 3, 2012. doi: 10.1001/jamapediatrics.2013.431
C1 [Merikangas, Kathleen R.; He, Jian-ping; Rapoport, Judith; Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA.
[Olfson, Mark] Columbia Univ, Sch Med, New York, NY USA.
RP Merikangas, KR (reprint author), Genet Epidemiol Res Branch, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA.
EM kathleen.merikangas@nih.gov
FU Intramural Research Program of the National Institute of Mental Health
[Z01 MH002808-08]; National Institute of Mental Health [U01-MH60220]
FX This work was supported by Intramural Research Program of the National
Institute of Mental Health grant Z01 MH002808-08. The NCS-A and the
larger program of related NCS surveys are supported by National
Institute of Mental Health grant U01-MH60220.
NR 62
TC 25
Z9 26
U1 1
U2 25
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6203
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD FEB
PY 2013
VL 167
IS 2
BP 141
EP 148
DI 10.1001/jamapediatrics.2013.431
PG 8
WC Pediatrics
SC Pediatrics
GA 115FQ
UT WOS:000316798400007
PM 23403911
ER
PT J
AU Blanco, C
Krueger, RF
Hasin, DS
Liu, SM
Wang, S
Kerridge, BT
Saha, T
Olfson, M
AF Blanco, Carlos
Krueger, Robert F.
Hasin, Deborah S.
Liu, Shang-Min
Wang, Shuai
Kerridge, Bradley T.
Saha, Tulshi
Olfson, Mark
TI Mapping Common Psychiatric Disorders Structure and Predictive Validity
in the National Epidemiologic Survey on Alcohol and Related Conditions
SO JAMA PSYCHIATRY
LA English
DT Article
ID INTERVIEW SCHEDULE AUDADIS; COMORBIDITY SURVEY REPLICATION;
ENVIRONMENTAL RISK-FACTORS; GENERAL-POPULATION SAMPLE; DSM-IV DISORDERS;
MENTAL-DISORDERS; DRUG MODULES; EXTERNALIZING PSYCHOPATHOLOGY;
PERSONALITY-DISORDERS; META-STRUCTURE
AB Context: Clinical experience and factor analytic studies suggest that some psychiatric disorders may be more closely related to one another, as indicated by the frequency of their co-occurrence, which may have etiologic and treatment implications.
Objective: To construct a virtual space of common psychiatric disorders, spanned by factors reflecting major psychopathologic dimensions, and locate psychiatric disorders in that space, as well as to examine whether the location of disorders at baseline predicts the prevalence and incidence of disorders at 3-year follow-up.
Design, Setting, and Patients: A total of 34 653 individuals participated in waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions.
Main Outcome Measures: The distance between disorders at wave 1, calculated using the loadings of the factors spanning the space of disorders as coordinates. This distance was correlated with the adjusted odds ratios for age, sex, and race/ethnicity of the prevalence and incidence of Axis 1 disorders in wave 2, with the aim of determining whether smaller distances between disorders at wave 1 predicts higher disorder prevalence and incidence at wave 2.
Results: A model with 3 correlated factors provided an excellent fit (Comparative Fit Index = 0.99, Tucker-Lewis Index = 0.98, root mean square error of approximation = 0.008) for the structure of common psychiatric disorders and was used to span the space of disorders. Distances ranged from 0.070 (between drug abuse and dysthymia) to 1.032 (between drug abuse and avoidant personality disorder). The correlation of distance between disorders in wave 1 with adjusted odds ratios of prevalence in wave 2 was -0.56. The correlation of distance in wave 1 with adjusted odds ratios of incidence in wave 2 was -0.57.
Conclusions: Mapping psychiatric disorders can be used to quantify the distances among disorders. Proximity in turn can be used to predict prospectively the incidence and prevalence of Axis I disorders. JAMA Psychiatry. 2013;70(2):199-208. Published online December 24, 2012. doi:10.1001/jamapsychiatry.2013.281
C1 [Blanco, Carlos; Hasin, Deborah S.; Liu, Shang-Min; Wang, Shuai; Olfson, Mark] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[Hasin, Deborah S.] Columbia Univ Coll Phys & Surg, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
[Blanco, Carlos; Hasin, Deborah S.; Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Krueger, Robert F.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
[Kerridge, Bradley T.] Univ Maryland, Dept Epidemiol & Biostat, Sch Publ Hlth, College Pk, MD 20742 USA.
[Saha, Tulshi] NIAAA, Intramural Lab Epidemiol & Biometry, Rockville, MD 20852 USA.
RP Blanco, C (reprint author), Columbia Univ Coll Phys & Surg, Dept Psychiat, 1051 Riverside Dr,Unit 69, New York, NY 10032 USA.
EM cb255@columbia.edu
RI Blanco, Carlos/I-4906-2013;
OI Blanco, Carlos/0000-0001-6187-3057; Kerridge,
Bradley/0000-0003-0459-9439
FU Eli Lilly and Company; Bristol-Myers Squibb; National Institute on
Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; National
Institutes of Health [DA019606, DA020783, DA023200, DA023973, CA133050,
MH082773, AA014223, AA018111, F31DA025377]; New York State Psychiatric
Institute
FX Dr Olfson has worked on grants from Eli Lilly and Company and
Bristol-Myers Squibb to Columbia University.; The National Epidemiologic
Survey on Alcohol and Related Conditions was sponsored by the National
Institute on Alcohol Abuse and Alcoholism, with supplemental support
from the National Institute on Drug Abuse. Work on this article was
supported by grants DA019606, DA020783, DA023200, DA023973, CA133050,
and MH082773 to Dr Blanco, AA014223 and AA018111 to Dr Hasin, and
F31DA025377 to Mr Kerridge from the National Institutes of Health, and
the New York State Psychiatric Institute (Drs Blanco, Hasin, and
Olfson).
NR 53
TC 38
Z9 38
U1 0
U2 12
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-622X
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD FEB
PY 2013
VL 70
IS 2
BP 199
EP 208
DI 10.1001/jamapsychiatry.2013.281
PG 10
WC Psychiatry
SC Psychiatry
GA 114GQ
UT WOS:000316729500009
PM 23266570
ER
PT J
AU Wang, YC
Graubard, BI
Rosenberg, MA
Kuntz, KM
Zauber, AG
Kahle, L
Schechter, CB
Feuer, EJ
AF Wang, Y. Claire
Graubard, Barry I.
Rosenberg, Marjorie A.
Kuntz, Karen M.
Zauber, Ann G.
Kahle, Lisa
Schechter, Clyde B.
Feuer, Eric J.
TI Derivation of Background Mortality by Smoking and Obesity in Cancer
Simulation Models
SO MEDICAL DECISION MAKING
LA English
DT Article
DE life tables; background mortality; cancer simulation
ID EXCESS DEATHS; UNDERWEIGHT; OVERWEIGHT; WEIGHT
AB Background. Simulation models designed to evaluate cancer prevention strategies make assumptions on background mortality-the competing risk of death from causes other than the cancer being studied. Researchers often use the U. S. life tables and assume homogeneous other-cause mortality rates. However, this can lead to bias because common risk factors such as smoking and obesity also predispose individuals for deaths from other causes such as cardiovascular disease. Methods. We obtained calendar year-, age-, and sex-specific other-cause mortality rates by removing deaths due to a specific cancer from U. S. all-cause life tables. Prevalence across 12 risk factor groups (3 smoking [never, past, and current smoker] and 4 body mass index [BMI] categories [<25, 25-30, 30-35, 35+ kg/m(2)]) were estimated from national surveys (National Health and Nutrition Examination Surveys [NHANES] 1971-2004). Using NHANES linked mortality data, we estimated hazard ratios for death by BMI/smoking using a Poisson regression model. Finally, we combined these results to create 12 sets of BMI and smoking-specific other-cause life tables for U. S. adults aged 40 years and older that can be used in simulation models of lung, colorectal, or breast cancer. Results. We found substantial differences in background mortality when accounting for BMI and smoking. Ignoring the heterogeneity in background mortality in cancer simulation models can lead to underestimation of competing risk of deaths for higher-risk individuals (e. g., male, 60-year old, white obese smokers) by as high as 45%. Conclusion. Not properly accounting for competing risks of death may introduce bias when using simulation modeling to evaluate population health strategies for prevention, screening, or treatment. Further research is warranted on how these biases may affect cancer-screening strategies targeted at high-risk individuals.
C1 [Wang, Y. Claire] Columbia Mailman Sch Publ Hlth, Dept Hlth Policy & Management, New York, NY 10032 USA.
[Graubard, Barry I.; Feuer, Eric J.] NCI, Washington, DC USA.
[Rosenberg, Marjorie A.] Univ Wisconsin, Dept Actuarial Sci Risk Management & Insurance, Madison, WI USA.
[Rosenberg, Marjorie A.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA.
[Kuntz, Karen M.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA.
[Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Kahle, Lisa] IMS Inc, Washington, DC USA.
[Schechter, Clyde B.] Albert Einstein Coll Med, New York, NY USA.
RP Wang, YC (reprint author), Columbia Mailman Sch Publ Hlth, Dept Hlth Policy & Management, 600 W 168th St,6th Floor, New York, NY 10032 USA.
EM ycw2102@columbia.edu
FU National Cancer Institute [NIH U01 CA115953]; Clinical and Translational
Science Award (CTSA) program of the National Center for Research
Resources [NIH 1UL1RR025011]
FX Received 9 December 2011 from the Department of Health Policy and
Management, Columbia Mailman School of Public Health, New York, NY, USA
(YCW); National Cancer Institute, Washington, DC, USA (BIG, EJF);
Departments of Actuarial Science, Risk Management and Insurance and
Biostatics and Medical Informatics, University of Wisconsin-Madison,
Madison, WI, USA (MAR); Division of Health Policy and Management, School
of Public Health, University of Minnesota, Minneapolis, MN, USA (KMK);
Memorial Sloan-Kettering Cancer Center, New York, NY, USA (AGZ); IMS,
Inc., Washington, DC, USA (LK); and Albert Einstein College of Medicine,
New York, NY, USA (CBS). An earlier version of this work was presented
at the 29th Annual Meeting of the Society for Medical Decision Making.
This work was supported in part by grants from the National Cancer
Institute (NIH U01 CA115953) and from the Clinical and Translational
Science Award (CTSA) program of the National Center for Research
Resources (Dr. Rosenberg, NIH 1UL1RR025011). This work is solely the
responsibility of the authors and does not represent official views of
the National Cancer Institute. Revision accepted for publication 1 June
2012.
NR 16
TC 1
Z9 1
U1 0
U2 8
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-989X
J9 MED DECIS MAKING
JI Med. Decis. Mak.
PD FEB
PY 2013
VL 33
IS 2
BP 176
EP 197
DI 10.1177/0272989X12458725
PG 22
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA 113QZ
UT WOS:000316684200007
PM 23132901
ER
PT J
AU Di, LJ
Byun, JS
Wong, MM
Wakano, C
Taylor, T
Bilke, S
Baek, S
Hunter, K
Yang, H
Lee, M
Zvosec, C
Khramtsova, G
Cheng, F
Perou, CM
Miller, CR
Raab, R
Olopade, OI
Gardner, K
AF Di, Li-Jun
Byun, Jung S.
Wong, Madeline M.
Wakano, Clay
Taylor, Tara
Bilke, Sven
Baek, Songjoon
Hunter, Kent
Yang, Howard
Lee, Maxwell
Zvosec, Cecilia
Khramtsova, Galina
Cheng, Fan
Perou, Charles M.
Miller, C. Ryan
Raab, Rachel
Olopade, Olufunmilayo I.
Gardner, Kevin
TI Genome-wide profiles of CtBP link metabolism with genome stability and
epithelial reprogramming in breast cancer
SO NATURE COMMUNICATIONS
LA English
DT Article
ID MESENCHYMAL TRANSITION; MOLECULAR PORTRAITS; NADH CONCENTRATION;
COREPRESSOR CTBP; CO-REPRESSOR; STEM-CELLS; EXPRESSION; COMPLEX; LSD1;
HALLMARKS
AB The C-terminal binding protein (CtBP) is a NADH-dependent transcriptional repressor that links carbohydrate metabolism to epigenetic regulation by recruiting diverse histone-modifying complexes to chromatin. Here global profiling of CtBP in breast cancer cells reveals that it drives epithelial-to-mesenchymal transition, stem cell pathways and genome instability. CtBP expression induces mesenchymal and stem cell-like features, whereas CtBP depletion or caloric restriction reverses gene repression and increases DNA repair. Multiple members of the CtBP-targeted gene network are selectively downregulated in aggressive breast cancer subtypes. Differential expression of CtBP-targeted genes predicts poor clinical outcome in breast cancer patients, and elevated levels of CtBP in patient tumours predict shorter median survival. Finally, both CtBP promoter targeting and gene repression can be reversed by small molecule inhibition. These findings define broad roles for CtBP in breast cancer biology and suggest novel chromatin-based strategies for pharmacologic and metabolic intervention in cancer.
C1 [Di, Li-Jun; Byun, Jung S.; Wong, Madeline M.; Wakano, Clay; Taylor, Tara; Bilke, Sven; Gardner, Kevin] NCI, Genet Branch, Bethesda, MD 20892 USA.
[Baek, Songjoon] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA.
[Hunter, Kent] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Yang, Howard; Lee, Maxwell] NCI, Lab Populat Genet, Bethesda, MD 20892 USA.
[Zvosec, Cecilia; Khramtsova, Galina; Olopade, Olufunmilayo I.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Cheng, Fan; Perou, Charles M.; Miller, C. Ryan] Univ N Carolina, Lineberger Comprehens Canc Care Ctr, Chapel Hill, NC 27599 USA.
[Raab, Rachel] E Carolina Univ, Leo W Jenkins Canc Ctr, Greenville, NC 27834 USA.
RP Gardner, K (reprint author), NCI, Genet Branch, Bethesda, MD 20892 USA.
EM gardnerk@mail.nih.gov
RI Di, Li-jun/B-3352-2011; Miller, Ryan/B-9365-2008;
OI Miller, Ryan/0000-0002-0096-8762; Perou, Charles/0000-0001-9827-2247
FU US National Institutes of Health; US National Cancer Institute; US
National Institute on Aging; US National Institute on Minority Health
and Health Disparities; University of Chicago Breast Cancer SPORE [P50
CA125183]
FX This research was supported by the Intramural Research Program of the US
National Institutes of Health, the US National Cancer Institute, the US
National Institute on Aging, the US National Institute on Minority
Health and Health Disparities, and the University of Chicago Breast
Cancer SPORE P50 CA125183.
NR 57
TC 35
Z9 35
U1 2
U2 21
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD FEB
PY 2013
VL 4
AR 1449
DI 10.1038/ncomms2438
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 112TL
UT WOS:000316616400025
PM 23385593
ER
PT J
AU Knox, SM
Lombaert, IMA
Haddox, CL
Abrams, SR
Cotrim, A
Wilson, AJ
Hoffman, MP
AF Knox, Sarah M.
Lombaert, Isabelle M. A.
Haddox, Candace L.
Abrams, Shaun R.
Cotrim, Ana
Wilson, Adrian J.
Hoffman, Matthew P.
TI Parasympathetic stimulation improves epithelial organ regeneration
SO NATURE COMMUNICATIONS
LA English
DT Article
ID GLAND BRANCHING MORPHOGENESIS; SUBMANDIBULAR-GLAND; GDNF FAMILY; NEURON
DEVELOPMENT; NERVOUS-SYSTEM; DISTINCT ROLES; STEM-CELLS; NEURTURIN;
GROWTH; GENE
AB Parasympathetic nerves are a vital component of the progenitor cell niche during development, maintaining a pool of progenitors for organogenesis. Injured adult organs do not regenerate after parasympathectomy, and there are few treatments to improve organ regeneration, particularly after damage by therapeutic irradiation. Here we show that restoring parasympathetic function with the neurotrophic factor neurturin increases epithelial organ regeneration after damage. We use mouse salivary gland explant culture containing fluorescently labelled progenitors, and injure the tissue with irradiation. The progenitors survive, parasympathetic function is diminished and epithelial apoptosis reduces the expression of neurturin, which increases neuronal apoptosis. Treatment with neurturin reduces neuronal apoptosis, restores parasympathetic function and increases epithelial regeneration. Furthermore, adult human salivary glands damaged by irradiation also have reduced parasympathetic innervation. We propose that neurturin will protect the parasympathetic nerves from damage and improve organ regeneration. This concept may be applicable for other organs where parasympathetic innervation influences their function.
C1 [Knox, Sarah M.; Lombaert, Isabelle M. A.; Haddox, Candace L.; Abrams, Shaun R.; Wilson, Adrian J.; Hoffman, Matthew P.] NIDCR, Matrix & Morphogenesis Sect, LCDB, NIH, Bethesda, MD 20892 USA.
[Cotrim, Ana] NIDCR, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Hoffman, MP (reprint author), NIDCR, Matrix & Morphogenesis Sect, LCDB, NIH, 30 Convent Dr, Bethesda, MD 20892 USA.
EM mhoffman@mail.nih.gov
OI Haddox, Candace/0000-0003-4223-0632; Knox, Sarah/0000-0002-7567-083X
FU Intramural Research Program of the National Institute of Dental and
Craniofacial Research, NIH
FX We would like to thank Dr Bruce Baum for helpful discussions and for
providing human tissue samples. We would also like to thank Dr L. M.
Angerer, Dr K. M. Yamada, Dr W. M. Knosp and S. Powers for discussions
and critical reading of this manuscript. The study was supported by the
Intramural Research Program of the National Institute of Dental and
Craniofacial Research, NIH.
NR 29
TC 50
Z9 51
U1 1
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD FEB
PY 2013
VL 4
AR 1494
DI 10.1038/ncomms2493
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 112TL
UT WOS:000316616400064
PM 23422662
ER
PT J
AU Liu, XB
Cotrim, A
Teos, L
Zheng, CY
Swaim, W
Mitchell, J
Mori, Y
Ambudkar, I
AF Liu, Xibao
Cotrim, Ana
Teos, Leyla
Zheng, Changyu
Swaim, William
Mitchell, James
Mori, Yasuo
Ambudkar, Indu
TI Loss of TRPM2 function protects against irradiation-induced salivary
gland dysfunction
SO NATURE COMMUNICATIONS
LA English
DT Article
ID QUALITY-OF-LIFE; RADIATION-INDUCED XEROSTOMIA; NECK-CANCER;
POLY(ADP-RIBOSE) POLYMERASE; OXIDATIVE STRESS; IMMUNE-SYSTEM; MOUSE
MODEL; TEMPOL; HEAD; PEROXYNITRITE
AB Xerostomia as a result of salivary gland damage is a permanent and debilitating side effect of radiotherapy for head and neck cancers. Effective treatments for protecting, or restoring, salivary gland function are not available. Here we report that irradiation treatment leads to activation of the calcium-permeable channel, transient potential melastatin-like 2 (TRPM2), via stimulation of poly-ADP-ribose polymerase. Importantly, irradiation induced an irreversible loss of salivary gland fluid secretion in TRPM2+/+ mice while a transient loss was seen in TRPM2-/- mice with >60% recovery by 30 days after irradiation. Treatment of TRPM2+/+ mice with the free radical scavenger Tempol or the PARP1 inhibitor 3-aminobenzamide attenuated irradiation-induced activation of TRPM2 and induced significant recovery of salivary fluid secretion. Furthermore, TPL (4-hydroxy-2,2,6,6-tetra-methylpiperidine-N-oxyl) induced complete recovery of function in irradiated TRPM2-/- mice. These novel data demonstrate that TRPM2 is activated by irradiation, via PARP1 activation, and contributes to irreversible loss of salivary gland function.
C1 [Liu, Xibao; Teos, Leyla; Swaim, William; Ambudkar, Indu] NCI, Secretory Physiol Sect, NIH, Bethesda, MD 20892 USA.
[Cotrim, Ana; Zheng, Changyu] NCI, Translat Res Core, Mol Physiol & Therapeut Branch, Natl Inst Dent & Craniofacial Res,NIH, Bethesda, MD 20892 USA.
[Mitchell, James] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
[Mori, Yasuo] Kyoto Univ, Grad Sch Engn, Dept Synthet Chem & Biol Chem, Mol Biol Lab, Kyoto 6158510, Japan.
RP Ambudkar, I (reprint author), NCI, Secretory Physiol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM indu.ambudkar@nih.gov
FU NIDCR-DIR
FX We acknowledge funding for this work from NIDCR-DIR (for IA). We thank
Hwei Ling Ong and Biman Paria for their help during the course of this
study.
NR 49
TC 14
Z9 14
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD FEB
PY 2013
VL 4
AR 1515
DI 10.1038/ncomms2526
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 112TL
UT WOS:000316616400085
PM 23443543
ER
PT J
AU Wu, T
Wang, CD
Wang, J
Hallett, M
Zang, YF
Chan, P
AF Wu, Tao
Wang, Chaodong
Wang, Jue
Hallett, Mark
Zang, Yufeng
Chan, Piu
TI Preclinical and clinical neural network changes in SCA2 parkinsonism
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Parkinsonism; SCA2 mutation; Functional connectivity; Basal ganglia
motor circuits; Compensation
ID SPINOCEREBELLAR ATAXIA TYPE-2; EXTERNALLY TRIGGERED MOVEMENTS; BASAL
GANGLIA; FUNCTIONAL CONNECTIVITY; COMPENSATORY MECHANISMS; DISEASE;
MOTOR; CARRIERS; CIRCUITS; ALLELE
AB Background: The pathophysiological changes before the presentation of clinical symptoms in parkinsonism are unclear. In this study, we investigated neural network modulations in persons in the preclinical stage of familial parkinsonism, and how the network interactions change at the clinical stage.
Methods: We performed functional MRI in a family with SCA2 mutation, including 9 asymptomatic carriers and 10 mutation carriers with parkinsonian symptoms. Functional connectivity from the posterior putamen bilaterally and rostral supplementary motor area was used to explore network interactions in the subjects.
Results: Both the asymptomatic carriers and patients had decreased connectivity within the basal ganglia-thalamus-cortical motor loop compared to controls. The asymptomatic carriers showed extensively increased connectivity compared to controls, including the cortico-cortical motor, cortico-cerebellar, cortico-brainstem, and part of the basal ganglia-thalamus-cortical motor circuits. In contrast, the connectivity of most of these networks was decreased in the patients. These abnormalities were relatively normalized after levodopa administration.
Conclusions: In the preclinical stage of SCA2 parkinsonism, the connectivity of a part of the basal ganglia motor loop is weakened as a consequence of dopaminergic deficits; meanwhile, the connectivity of other large-scale brain networks is strengthened presumably to compensate for the dysfunction of the basal ganglia to maintain brain function in the early stage of dopaminergic deficits. The simultaneous effects of progressive disruption of basal ganglia motor circuits and failure of compensatory mechanisms as dopaminergic dysfunction progresses may contribute to the onset of clinical symptoms. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Wu, Tao; Wang, Chaodong; Chan, Piu] Capital Med Univ, Xuanwu Hosp, Dept Neurobiol,Beijing Inst Geriatr, Key Lab Neurodegenerat Disorders,Minist Educ, Beijing 100053, Peoples R China.
[Wang, Jue; Zang, Yufeng] Hangzhou Normal Univ, Affiliated Hosp, Ctr Cognit & Brain Disorders, Hangzhou, Zhejiang, Peoples R China.
[Hallett, Mark] NINDS, NIH, Med Neurol Branch, Human Motor Control Sect, Bethesda, MD 20892 USA.
RP Chan, P (reprint author), Capital Med Univ, Xuanwu Hosp, Dept Neurobiol,Beijing Inst Geriatr, Key Lab Neurodegenerat Disorders,Minist Educ, Beijing 100053, Peoples R China.
EM pbchan90@gmail.com
RI ZANG, Yu-Feng/J-1558-2012
OI ZANG, Yu-Feng/0000-0003-1833-8010
FU National Science Foundation of China [30570530, 30870693, 81071012]
FX This work was supported by grants from the National Science Foundation
of China (30570530, 30870693, and 81071012).
NR 30
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U1 0
U2 11
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD FEB
PY 2013
VL 19
IS 2
BP 158
EP 164
DI 10.1016/j.parkreldis.2012.08.011
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 115RG
UT WOS:000316829000004
PM 23000299
ER
PT J
AU Lee, HJ
Lee, OJ
Jang, KT
Bae, YK
Chung, JY
Eom, DW
Kim, JM
Yu, E
Hong, SM
AF Lee, Hee Jin
Lee, Ok-Jun
Jang, Kee-Taek
Bae, Young Kyung
Chung, Joon-Yong
Eom, Dae Woon
Kim, Joon Mee
Yu, Eunsil
Hong, Seung-Mo
TI Combined Loss of E-cadherin and Aberrant beta-Catenin Protein Expression
Correlates With a Poor Prognosis for Small Intestinal Adenocarcinomas
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE Small intestine; Adenocarcinoma; E-cadherin; beta-catenin;
Immunohistochemistry; Prognosis
ID PANCREATIC INTRAEPITHELIAL NEOPLASIA; SMALL-BOWEL; IMMUNOHISTOCHEMICAL
ANALYSIS; CARCINOMAS; CANCER; MUTATIONS; PATHOGENESIS; ACTIVATION;
PHENOTYPE; DELETIONS
AB Small intestinal adenocarcinomas (SLACs) are rare, and their molecular pathogenesis is largely unknown. To define the roles of E-cadherin and beta-catenin, we performed immunohistochemistry for E-cadherin and beta-catenin in 194 surgically resected SIACs with tissue microarrays and compared the data with clinicopathologic factors, including survival rates of patients with SIAC. Loss of E-cadherin expression and aberrant beta-catenin expression were observed in 41.8% (81/194 cases) and 40.7% (79/194 cases) of SIACs, respectively. Combined loss of E-cadherin and aberrant beta-catenin expression was observed in 24.2% (47/194 cases) of SIACs, and this feature was most frequently observed in mucinous adenocarcinomas and signet ring cell carcinomas (P < .001), poorly differentiated and undifferentiated carcinomas (P < .001), and tumors with advanced pT classification (P = .03). Survival times for patients with SIAC with both loss of E-cadherin and aberrant beta-catenin expression (median, 13.9 months) were significantly shorter than those for patients without aberrant expression of both proteins (49.9 months), as determined by univariate (P < .001) and multivariate (P = .01) analyses. In conclusion, loss of E-cadherin and aberrant beta-catenin expression correlate with poorly differentiated tumors, advanced T classification, and decreased patient survival time; therefore, it could be a prognostic factor in patients with SIAC.
C1 [Lee, Hee Jin; Yu, Eunsil; Hong, Seung-Mo] Univ Ulsan, Coll Med, Dept Pathol, Asan Med Ctr, Seoul 138736, South Korea.
[Lee, Ok-Jun] Chungbuk Natl Univ, Coll Med, Dept Pathol, Cheongju, South Korea.
[Jang, Kee-Taek] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul, South Korea.
[Bae, Young Kyung] Yeungnam Univ, Coll Med, Dept Pathol, Taegu, South Korea.
[Chung, Joon-Yong] NCI, Appl Mol Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Chung, Joon-Yong] NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Eom, Dae Woon] Univ Ulsan, Coll Med, Gangneung Asan Hosp, Dept Pathol, Kangnung, South Korea.
[Kim, Joon Mee] Inha Univ, Coll Med, Dept Pathol, Inchon, South Korea.
RP Hong, SM (reprint author), Univ Ulsan, Coll Med, Dept Pathol, Asan Med Ctr, 388-1 Pungnap Dong, Seoul 138736, South Korea.
EM smhong28@gmail.com
OI Hong, Seung-Mo/0000-0002-8888-6007
FU National Research Foundation of Korea (NRF); Ministry of Education,
Science, and Technology [2010-0004807]; Asan Institute for Life
Sciences, Seoul, South Korea [2013-554]
FX This research was supported by the Basic Science Research Program
through the National Research Foundation of Korea (NRF) and funded by
the Ministry of Education, Science, and Technology (2010-0004807) and a
grant (2013-554) from the Asan Institute for Life Sciences, Seoul, South
Korea.
NR 29
TC 12
Z9 13
U1 0
U2 9
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD FEB
PY 2013
VL 139
IS 2
BP 167
EP 176
DI 10.1309/AJCPS54RTFCTHGWX
PG 10
WC Pathology
SC Pathology
GA 109LD
UT WOS:000316369100006
PM 23355201
ER
PT J
AU Valentino, C
Kendrick, S
Johnson, N
Gascoyne, R
Chan, WC
Weisenburger, D
Braziel, R
Cook, JR
Tubbs, R
Campo, E
Rosenwald, A
Ott, G
Delabie, J
Jaffe, E
Zhang, WJ
Brunhoeber, P
Nitta, H
Grogan, T
Rimsza, L
AF Valentino, Carlo
Kendrick, Samantha
Johnson, Nathalie
Gascoyne, Randy
Chan, Wing C.
Weisenburger, Dennis
Braziel, Rita
Cook, James R.
Tubbs, Raymond
Campo, Elias
Rosenwald, Andreas
Ott, German
Delabie, Jan
Jaffe, Elaine
Zhang, Wenjun
Brunhoeber, Patrick
Nitta, Hiro
Grogan, Tom
Rimsza, Lisa
TI Colorimetric In Situ Hybridization Identifies MYC Gene Signal Clusters
Correlating With Increased Copy Number, mRNA, and Protein in Diffuse
Large B-Cell Lymphoma
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE MYC; Colorimetric; In situ hybridization; Lymphoma; Ploidy; Gene
expression; Immunohistochemistry; Survival
ID POOR-PROGNOSIS; R-CHOP; AMPLIFICATION; REARRANGEMENT; EXPRESSION;
PREDICT; RITUXIMAB; SURVIVAL; DLBCL; ALK
AB Abnormalities of the MYC oncogene on chromosome 8 are characteristic of Burkitt lymphoma and other aggressive B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). We recently described a colorimetric in situ hybridization (CISH) method for detecting extra copies of the MYC gene in DLBCL and the frequent occurrence of excess copies of discrete MYC signals in the context of diploidy or polyploidy of chromosome 8, which correlated with increased mRNA signals. We further observed enlarged MYC signals, which were counted as a single gene copy but, by their dimension and unusual shape, likely consisted of "clusters" of MYC genes. In this study, we sought to further characterize these clusters of MYC signals by determining whether the presence of these correlated with other genetic features, mRNA levels, protein, and overall survival. We found that MYC clusters correlated with an abnormal MYC locus and with increased mRNA. MYC mRNA correlated with protein levels, and both increased mRNA and protein correlated with poorer overall survival. MYC clusters were seen in both the germinal center and activated B-cell subtypes of DLBCL. Clusters of MYC signals may be an underappreciated, but clinically important, feature of aggressive B-cell lymphomas with potential prognostic and therapeutic relevance.
C1 [Valentino, Carlo; Kendrick, Samantha; Grogan, Tom; Rimsza, Lisa] Univ Arizona, Coll Med, Dept Pathol, Tucson, AZ 85724 USA.
[Johnson, Nathalie] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Gascoyne, Randy] British Columbia Canc Agcy, Pathol & Lab Med, Vancouver, BC V5Z 4E6, Canada.
[Gascoyne, Randy] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada.
[Gascoyne, Randy] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Chan, Wing C.; Weisenburger, Dennis] Univ Nebraska, Med Ctr, Dept Pathol, Omaha, NE USA.
[Braziel, Rita] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR USA.
[Cook, James R.; Tubbs, Raymond] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44106 USA.
[Campo, Elias] Hosp Clin Barcelona, Barcelona, Spain.
[Rosenwald, Andreas] Univ Wurzburg, Dept Pathol, Wurzburg, Germany.
[Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany.
[Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.
[Delabie, Jan] Oslo Radium Hosp, Dept Pathol, Oslo, Norway.
[Jaffe, Elaine] NCI, Bethesda, MD 20892 USA.
[Zhang, Wenjun; Brunhoeber, Patrick; Nitta, Hiro; Grogan, Tom] Ventana Med Syst, Tucson, AZ USA.
RP Rimsza, L (reprint author), Univ Arizona, Coll Med, Dept Pathol, 1501 N Campbell Ave,Room 5208A,POB 245043, Tucson, AZ 85724 USA.
OI Jaffe, Elaine/0000-0003-4632-0301; Campo, elias/0000-0001-9850-9793;
Delabie, Jan/0000-0001-5023-0689
FU Ventana Medical Systems
FX Dr Grogan, Dr Brunhoeber, Dr Nitta, and Dr Zhang are employees of
Ventana Medical Systems, which produced the MYC and CEN8 probes and
funded a portion of this work.
NR 26
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U1 2
U2 7
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD FEB
PY 2013
VL 139
IS 2
BP 242
EP 254
DI 10.1309/AJCP2Z0TAGMUYJEB
PG 13
WC Pathology
SC Pathology
GA 109LD
UT WOS:000316369100014
PM 23355209
ER
PT J
AU Baker, SG
AF Baker, Stuart G.
TI Berrendero, J. R., and Carcamo, J. (2012), "The Tangent Classifier," The
American Statistician, 66, 185-194: Comment by Baker and Response
SO AMERICAN STATISTICIAN
LA English
DT Letter
C1 NCI, Bethesda, MD 20892 USA.
RP Baker, SG (reprint author), NCI, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 1
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 0003-1305
J9 AM STAT
JI Am. Stat.
PD FEB
PY 2013
VL 67
IS 1
BP 64
EP 65
PG 2
WC Statistics & Probability
SC Mathematics
GA 104FR
UT WOS:000315977800014
ER
PT J
AU Voortman, J
Harada, T
Chang, RP
Killian, JK
Suuriniemi, M
Smith, WI
Meltzer, PS
Lucchi, M
Wang, Y
Giaccone, G
AF Voortman, J.
Harada, T.
Chang, R. P.
Killian, J. K.
Suuriniemi, M.
Smith, W. I., Jr.
Meltzer, P. S.
Lucchi, M.
Wang, Y.
Giaccone, G.
TI Detection and Therapeutic Implications of c-Met Mutations in Small Cell
Lung Cancer and Neuroendocrine Tumors
SO CURRENT PHARMACEUTICAL DESIGN
LA English
DT Article
DE c-Met; mutation; neuroendocrine tumor; tyrosine kinase inhibitor
ID TYROSINE KINASE RECEPTOR; GROWTH-FACTOR RECEPTOR; JUXTAMEMBRANE DOMAIN;
SOMATIC MUTATIONS; AMPLIFICATION; ACTIVATION; INHIBITORS; PROTOONCOGENE;
RESISTANCE; GEFITINIB
AB Background. We evaluated the mutation status of c-Met in small cell lung cancer (SCLC) and neuroendocrine tumors (NET), for which relatively limited therapeutic targets have been explored.
Materials and Methods. c-Met was re-sequenced using cell lines and clinical samples. For in vitro studies, DNA constructs containing a juxtamembrane domain (JMD) and tyrosine kinase domain (TKD) were generated. Detected mutations were introduced into the construct and effects on c-Met phosphorylation and interaction with tyrosine kinase inhibitor drugs BMS777607 and SU11274 were assessed.
Results. 97 specimens were analyzed: 13 SCLC and 2 pulmonary carcinoid cell lines, 46 SCLC and 36 NET clinical specimens. Mutations were only detected in the JMD. No mutations were detected in the TKD. Found mutations consisted of the previously reported R988C and T1010I mutations. One novel JMD mutation, P996S, was detected in a SCLC specimen. The mutation rate in SCLC cell lines was 25% (31% including a derivative cell line), and 6.5% in clinical specimens. The mutation rate in NET was 8.3%. In vitro, there were no differences between wild type, R988C or T1010I mutants regarding c-Met phosphorylation at Y1003, located in the JMD, and at Y1234/1235, located in the TKD. BMS777607 and SU11274 were shown to inhibit phosphorylation of c-Met in wild type and R988C and T1010I mutants in a similar fashion.
Conclusions. In SCLC and neuroendocrine tumors MET mutations are relatively rare. Detected mutations were located in the juxtamembrane domain and were of no functional relevance as they did not influence c-Met phosphorylation, regardless of TKI treatment.
C1 [Voortman, J.; Harada, T.; Wang, Y.; Giaccone, G.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Chang, R. P.; Killian, J. K.; Suuriniemi, M.; Meltzer, P. S.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Smith, W. I., Jr.] Suburban Hosp, Dept Pathol, Bethesda, MD USA.
[Lucchi, M.] Univ Pisa, Div Thorac Surg, Cardiac & Thorac Dept, Pisa, Italy.
RP Giaccone, G (reprint author), NCI, Bldg 10 Magnuson CC,Room 12N226,10 Ctr Dr, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
RI Giaccone, Giuseppe/E-8297-2017;
OI Giaccone, Giuseppe/0000-0002-5023-7562; LUCCHI,
MARCO/0000-0001-9909-6820
FU Clinical and Molecular Profiling Core (CMPC), National Cancer Institute
FX Mutation studies were in part supported by the Clinical and Molecular
Profiling Core (CMPC), National Cancer Institute, with special thanks to
Marbin Pineda, Cancer Genetics Branch, National Cancer Institute.
NR 36
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U1 1
U2 8
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1381-6128
J9 CURR PHARM DESIGN
JI Curr. Pharm. Design
PD FEB
PY 2013
VL 19
IS 5
BP 833
EP 840
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 110NE
UT WOS:000316449900004
PM 22973954
ER
PT J
AU Mendive, S
Bornstein, MH
Sebastian, C
AF Mendive, Susana
Bornstein, Marc H.
Sebastian, Christian
TI The role of maternal attention-directing strategies in 9-month-old
infants attaining joint engagement
SO INFANT BEHAVIOR & DEVELOPMENT
LA English
DT Article
DE Joint attention; Mother-infant interaction; Scaffolding;
Attention-directing strategies; Sequential analysis
ID LANGUAGE-DEVELOPMENT; MOTHER-INFANT; CHILD; RESPONSIVENESS; COMPETENCE;
BEHAVIORS
AB Coordinated joint engagement (CJE) is a behavioral measure used in the infant-caregiver interaction paradigm to measure joint attention. To know how mothers scaffold infant attention to prompt joint engagement states, this study attempted to determine (a) which specific maternal attention-directing strategies facilitate CJE in mother-infant interactions and (b) how attention-directing strategies precede a range of infant engagement states. Free play in 33 low-SES dyads was analyzed sequentially, a method that reveals temporal relations between the behaviors involved in an interaction. Maintaining was the only strategy that preceded CJE, and Introducing and Redirecting preceded infant Engagement with Object, Onlooking, and Supported Joint Engagement. The results point to the scaffolding role of Maintaining and the mediating role of Introducing and Redirecting maternal strategies. To understand how low-SES infants attain CJE is important given the relation between joint attention and cognitive development. Implications of the results for interventions aimed at reducing socioeconomic inequities in early cognitive development are discussed. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Mendive, Susana] Univ Catolica Chile, Fac Educ Pontificia, Santiago, Chile.
[Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Sebastian, Christian] Pontificia Univ Catolica Chile, Escuela Psicol, Santiago, Chile.
RP Mendive, S (reprint author), Fac Educ, Av Vicuna Mackenna 4860, Macul, Santiago De Chi, Chile.
EM smendive@uc.cl
RI Mendive, Susana/B-2095-2017
OI Mendive, Susana/0000-0002-9436-3974
FU Intramural NIH HHS [ZIA HD001119-25, Z99 HD999999]
NR 52
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Z9 5
U1 1
U2 24
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0163-6383
J9 INFANT BEHAV DEV
JI Infant Behav. Dev.
PD FEB
PY 2013
VL 36
IS 1
BP 115
EP 123
DI 10.1016/j.infbeh.2012.10.002
PG 9
WC Psychology, Developmental
SC Psychology
GA 111QV
UT WOS:000316536700012
PM 23276727
ER
PT J
AU Fried, M
Avril, M
Chaturvedi, R
Fernandez, P
Lograsso, J
Narum, D
Nielsen, MA
Oleinikov, AV
Resende, M
Salanti, A
Saveria, T
Williamson, K
Dicko, A
Scherf, A
Smith, JD
Theander, TG
Duffy, PE
AF Fried, Michal
Avril, Marion
Chaturvedi, Richa
Fernandez, Pablo
Lograsso, Joseph
Narum, David
Nielsen, Morten A.
Oleinikov, Andrew V.
Resende, Mafalda
Salanti, Ali
Saveria, Tracy
Williamson, Kathryn
Dicko, Alassane
Scherf, Artur
Smith, Joseph D.
Theander, Thor G.
Duffy, Patrick E.
TI Multilaboratory Approach to Preclinical Evaluation of Vaccine Immunogens
for Placental Malaria
SO INFECTION AND IMMUNITY
LA English
DT Article
ID CHONDROITIN SULFATE-A; PREGNANCY-ASSOCIATED MALARIA; CROSS-REACTIVE
ANTIBODIES; FALCIPARUM-INFECTED ERYTHROCYTES; CSA-BINDING PARASITES;
PLASMODIUM-FALCIPARUM; BLOCKING ANTIBODIES; IMMUNOGLOBULIN-G; VAR2CSA;
DOMAINS
AB Pregnancy malaria is caused by Plasmodium falciparum-infected erythrocytes that adhere to the placental receptor chondroitin sulfate A (CSA) and sequester in the placenta; women become resistant to pregnancy malaria as they acquire antiadhesion antibodies that target surface proteins of placental parasites. VAR2CSA, a member of the P. falciparum EMP1 variant surface antigen family, is the leading candidate for a pregnancy malaria vaccine. Because VAR2CSA is a high-molecular-weight protein, a vaccine based on the full-length protein may not be feasible. An alternative approach has been to develop a vaccine targeting individual Duffy binding-like (DBL) domains. In this study, a consortium of laboratories under the Pregnancy Malaria Initiative compared the functional activity of antiadhesion antibodies elicited by different VAR2CSA domains and variants produced in prokaryotic and eukaryotic expression systems. Antisera were initially tested against laboratory lines of maternal parasites, and the most promising reagents were evaluated in the field against fresh placental parasite samples. Recombinant proteins expressed in Escherichia coli elicited antibody levels similar to those expressed in eukaryotic systems, as did the two allelic forms of the DBL4 and DBL5 domains. The procedures developed for this head-to-head comparison will be useful for future evaluation and down-selection of malaria vaccine immunogens.
C1 [Fried, Michal; Avril, Marion; Chaturvedi, Richa; Lograsso, Joseph; Oleinikov, Andrew V.; Saveria, Tracy; Williamson, Kathryn; Smith, Joseph D.; Duffy, Patrick E.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Fried, Michal; Narum, David; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
[Fernandez, Pablo; Scherf, Artur] Inst Pasteur, Unite Biol Interact Hote Parasite, Paris, France.
[Fernandez, Pablo; Scherf, Artur] CNRS URA2581, Paris, France.
[Nielsen, Morten A.; Resende, Mafalda; Salanti, Ali; Theander, Thor G.] Univ Copenhagen, Rigshosp, Copenhagen Univ Hosp, Ctr Med Parasitol, DK-2100 Copenhagen, Denmark.
[Dicko, Alassane] Univ Bamako, Immunoepidemiol Program IMEPP, Malaria Res & Training Ctr, Fac Med & Dent, Bamako, Mali.
RP Fried, M (reprint author), Seattle Biomed Res Inst, 4 Nickerson St, Seattle, WA 98109 USA.
EM michal.fried@nih.gov
RI Scherf, Artur/A-9674-2014; Theander, Thor/F-6714-2015;
OI Nielsen, Morten Agertoug/0000-0003-2668-4992; Theander, Thor
G./0000-0002-3509-7514
FU Bill & Melinda Gates Foundation [47029]; U.S. National Institutes of
Health [AI52059]; NIAID-NIH
FX This work was supported by a grant from the Bill & Melinda Gates
Foundation (grant 47029) and U.S. National Institutes of Health grant
AI52059 (to P.E.D.). This research was supported in part by the
Intramural Research Program of the NIAID-NIH.
NR 39
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Z9 19
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD FEB
PY 2013
VL 81
IS 2
BP 487
EP 495
DI 10.1128/IAI.01106-12
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 108RD
UT WOS:000316312800011
PM 23208604
ER
PT J
AU Kurtz, SL
Foreman, O
Bosio, CM
Anver, MR
Elkins, KL
AF Kurtz, Sherry L.
Foreman, Oded
Bosio, Catharine M.
Anver, Miriam R.
Elkins, Karen L.
TI Interleukin-6 Is Essential for Primary Resistance to Francisella
tularensis Live Vaccine Strain Infection
SO INFECTION AND IMMUNITY
LA English
DT Article
ID CELL-MEDIATED-IMMUNITY; ACUTE-PHASE RESPONSE; T-CELLS; IN-VIVO;
CHLAMYDIA-TRACHOMATIS; RESPIRATORY TULAREMIA; PULMONARY INFECTION;
GAMMA-INTERFERON; DENDRITIC CELLS; KNOCKOUT MICE
AB We employed Francisella tularensis live vaccine strain (LVS) to study mechanisms of protective immunity against intracellular pathogens and, specifically, to understand protective correlates. One potential molecular correlate identified previously was interleukin-6 (IL-6), a cytokine with pleotropic roles in immunity, including influences on T and B cell functions. Given its role as an immune modulator and the correlation with successful anti-LVS vaccination, we examined the role IL-6 plays in the host response to LVS. IL-6-deficient (IL-6 knockout [KO]) mice infected with LVS intradermally or intranasally or anti-IL-6-treated mice, showed greatly reduced 50% lethal doses compared to wild-type (WT) mice. Increased susceptibility was not due to altered splenic immune cell populations during infection or decreased serum antibody production, as IL-6 KO mice had similar compositions of each compared to WT mice. Although LVS-infected IL-6 KO mice produced much less serum amyloid A and haptoglobin (two acute-phase proteins) than WT mice, there were no other obvious pathophysiological differences between LVS-infected WT and IL-6 KO mice. IL-6 KO or WT mice that survived primary LVS infection also survived a high-dose LVS secondary challenge. Using an in vitro overlay assay that measured T cell activation, cytokine production, and abilities of primed splenocytes to control intracellular LVS growth, we found that IL-6 KO total splenocytes or purified T cells were slightly defective in controlling intracellular LVS growth but were equivalent in cytokine production. Taken together, IL-6 is an integral part of a successful immune response to primary LVS infection, but its exact role in precipitating adaptive immunity remains elusive.
C1 [Kurtz, Sherry L.; Elkins, Karen L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Foreman, Oded] Jackson Lab, Sacramento, CA USA.
[Bosio, Catharine M.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Anver, Miriam R.] SAIC Frederick Inc, Pathol Histotechnol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Elkins, KL (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
EM karen.elkins@fda.hhs.gov
RI Bosio, Catharine/D-7456-2015
FU National Institute of Allergy and Infectious Diseases
[Y1-AI-6153-01/224-06-1322]; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]
FX This project has been funded in part by an interagency agreement with
the National Institute of Allergy and Infectious Diseases
(Y1-AI-6153-01/224-06-1322) and by federal funds from the National
Cancer Institute, National Institutes of Health, under contract number
HHSN261200800001E.
NR 54
TC 20
Z9 20
U1 0
U2 12
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD FEB
PY 2013
VL 81
IS 2
BP 585
EP 597
DI 10.1128/IAI.01249-12
PG 13
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 108RD
UT WOS:000316312800022
PM 23230288
ER
PT J
AU Reinisch, W
Knobler, R
Rutgeerts, PJ
Ochsenkuhn, T
Anderson, F
von Tirpitz, C
Kaatz, M
van der Woude, CJ
Parenti, D
Mannon, PJ
AF Reinisch, Walter
Knobler, Robert
Rutgeerts, Paul J.
Ochsenkuehn, Thomas
Anderson, Frank
von Tirpitz, Christian
Kaatz, Martin
van der Woude, C. Janneke
Parenti, Dennis
Mannon, Peter J.
TI Extracorporeal Photopheresis (ECP) in Patients with Steroid-dependent
Crohn's Disease: An Open-label, Multicenter, Prospective Trial
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Article
DE extracorporeal photopheresis; Crohn's disease; steroid dependent
ID INFLAMMATORY-BOWEL-DISEASE; APOPTOTIC CELLS; T-CELLS; THERAPY;
METHOTREXATE
AB Background: Extracorporeal photopheresis (ECP) involves ex vivo leukocyte treatment with methoxsalen and UVA light to generate a tolerogenic response. A previous trial demonstrated that ECP permits corticosteroid withdrawal in steroid-dependent Crohn's disease (CD) patients who were in clinical remission. We studied the effect of ECP on steroid withdrawal in steroid-dependent CD.
Methods: Patients with CD for >= 6 months, in remission at baseline while on steroids, but who had failed at >= 1 steroid withdrawal were included. Patients received two ECP treatments every 2 weeks for the 24-week steroid tapering period and underwent steroid-tapering. Patients completing steroid tapering could receive maintenance ECP (two treatments/week) every month for 24 weeks.
Results: Thirty-one patients (Crohn's Disease Activity Index [CDAI] score 91; Inflammatory Bowel Disease Questionnaire [IBDQ] 172.5) were enrolled (baseline corticosteroid dose, 20 mg/day); 65% were refractory to/intolerant of anti-tumor necrosis factor (TNF) agents or immunosuppressants. After 24 weeks of ECP, 7 of 31 (22.6%) patients discontinued steroids while maintaining a CDAI of,150. At week 24, the steroid dose for the remaining patients on corticosteroids was 10 mg (P < 0.003 vs. baseline) with a CDAI of 110 and an IBDQ of 179. Following maintenance treatment, three patients remained in steroid-free remission. The 10 patients in the study and receiving ECP at week 48 had a steroid dose of 3.5 mg with a CDAI of 40 and an IBDQ of 188.
Conclusions: ECP permitted discontinuation or reduction of steroids in a population of refractory steroid-dependent CD patients. ECP may be useful in permitting steroid withdrawal in selected steroid-dependent CD patients. Ideally, these results need to be confirmed in a "sham-controlled" clinical trial. (Inflamm Bowel Dis 2013;19:293-300)
C1 [Reinisch, Walter; Knobler, Robert] Med Univ Vienna, A-1090 Vienna, Austria.
[Rutgeerts, Paul J.] Katholieke Univ Leuven, Louvain, Belgium.
[Ochsenkuehn, Thomas] Univ Munich, Munich, Germany.
[Anderson, Frank] LAIR Ctr, Vancouver, BC, Canada.
[von Tirpitz, Christian] Univ Ulm, D-89069 Ulm, Germany.
[Kaatz, Martin] Univ Jena, Jena, Germany.
[van der Woude, C. Janneke] Erasmus Univ, Rotterdam, Netherlands.
[Parenti, Dennis] Johnson & Johnson, Therakos, Raritan, NJ USA.
[Mannon, Peter J.] NIAID, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA.
RP Reinisch, W (reprint author), Med Univ Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM walter.reinisch@meduniwien.ac.at
FU Therakos, Inc., Raritan, NJ
FX Supported by a grant from Therakos, Inc., Raritan, NJ.
NR 16
TC 12
Z9 13
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1078-0998
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD FEB
PY 2013
VL 19
IS 2
BP 293
EP 300
DI 10.1002/ibd.23012
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 110MM
UT WOS:000316447300025
PM 22573600
ER
PT J
AU Swaroop, A
AF Swaroop, Anand
TI What's in a Name? RPGR Mutations Redefine the Genetic and Phenotypic
Landscape in Retinal Degenerative Diseases
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Editorial Material
ID RETINITIS-PIGMENTOSA
C1 NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
OI Swaroop, Anand/0000-0002-1975-1141
NR 6
TC 3
Z9 3
U1 0
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD FEB
PY 2013
VL 54
IS 2
BP 1417
EP 1417
DI 10.1167/iovs.13-11750
PG 1
WC Ophthalmology
SC Ophthalmology
GA 100BS
UT WOS:000315670300064
PM 23423174
ER
PT J
AU Bertelsen, RJ
Brantsaeter, AL
Haugen, M
Meltzer, HM
London, SJ
AF Bertelsen, Randi J.
Brantsaeter, Anne Lise
Haugen, Margaretha
Meltzer, Helle Margrethe
London, Stephanie J.
TI Maternal Probiotic Intake and Respiratory and Allergy Outcomes in Early
Childhood
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology
(AAAAI)
CY FEB 22-26, 2013
CL San Antonio, TX
SP Amer Acad Allergy, Asthma & Immunol (AAAAI)
C1 [Bertelsen, Randi J.; Brantsaeter, Anne Lise; Haugen, Margaretha; Meltzer, Helle Margrethe] Norwegian Inst Publ Hlth, Oslo, Norway.
[Bertelsen, Randi J.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[London, Stephanie J.] NIEHS, Res Triangle Pk, NC 27709 USA.
RI Brantsaeter, Anne Lise/H-7014-2016
OI Brantsaeter, Anne Lise/0000-0001-6315-7134
NR 0
TC 0
Z9 0
U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2013
VL 131
IS 2
SU S
BP AB129
EP AB129
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 111WC
UT WOS:000316550800461
ER
PT J
AU Busse, P
Cohn, R
Salo, PM
Zeldin, DC
AF Busse, Paula
Cohn, Richard
Salo, Paivi M.
Zeldin, Darryl C.
TI Characteristics of Allergic Sensitization Among Adult Asthmatics Older
Than 55 Years: Results From the National Health and Nutrition
Examination Survey 2005-2006
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology
(AAAAI)
CY FEB 22-26, 2013
CL San Antonio, TX
SP Amer Acad Allergy, Asthma & Immunol (AAAAI)
C1 [Busse, Paula] Mt Sinai Sch Med, New York, NY USA.
[Cohn, Richard] SRA Int Inc, Durham, NC USA.
[Salo, Paivi M.; Zeldin, Darryl C.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2013
VL 131
IS 2
SU S
BP AB160
EP AB160
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 111WC
UT WOS:000316550800564
ER
PT J
AU Chang, LJ
Mendoza, F
Saunders, J
Plummer, S
Yamshchikov, GV
Ledgerwood, JE
Graham, BS
AF Chang, Lee-Jah
Mendoza, Floreliz
Saunders, Jamie
Plummer, Sarah
Yamshchikov, Galina V.
Ledgerwood, Julie E.
Graham, Barney S.
TI VRC 311: Phase I Clinical Trial of a Virus-Like Particle Chikungunya
Vaccine in Healthy Adults
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology
(AAAAI)
CY FEB 22-26, 2013
CL San Antonio, TX
SP Amer Acad Allergy, Asthma & Immunol (AAAAI)
C1 [Chang, Lee-Jah; Mendoza, Floreliz; Saunders, Jamie; Plummer, Sarah; Yamshchikov, Galina V.; Ledgerwood, Julie E.; Graham, Barney S.] NIAID, NIH, VRC, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2013
VL 131
IS 2
SU S
BP AB330
EP AB330
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 111WC
UT WOS:000316550800858
ER
PT J
AU Chinn, I
Milner, JD
Scheinberg, P
Douek, D
Markert, ML
AF Chinn, Ivan
Milner, Joshua D.
Scheinberg, Phillip
Douek, Daniel
Markert, M. Louise
TI Thymus Transplantation Restores the Repertoire of Foxp3(+) T Cells in
Complete DiGeorge Anomaly
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology
(AAAAI)
CY FEB 22-26, 2013
CL San Antonio, TX
SP Amer Acad Allergy, Asthma & Immunol (AAAAI)
C1 [Chinn, Ivan; Markert, M. Louise] Duke Univ, Med Ctr, Durham, NC USA.
[Milner, Joshua D.; Scheinberg, Phillip; Markert, M. Louise] NIAID, Bethesda, MD 20892 USA.
[Scheinberg, Phillip] NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2013
VL 131
IS 2
SU S
BP AB196
EP AB196
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 111WC
UT WOS:000316550800698
ER
PT J
AU Crank, MC
Hu-Li, J
Paul, WE
AF Crank, Michelle C.
Hu-Li, Jane
Paul, William E.
TI IL-1-Beta Maintains IL-2R-Alpha (CD25) Expression On the Surface of Th17
Cells and Partially Reverses IL-2 Mediated Inhibition of Th17
Differentiation
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology
(AAAAI)
CY FEB 22-26, 2013
CL San Antonio, TX
SP Amer Acad Allergy, Asthma & Immunol (AAAAI)
C1 [Crank, Michelle C.; Hu-Li, Jane; Paul, William E.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2013
VL 131
IS 2
SU S
BP AB7
EP AB7
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 111WC
UT WOS:000316550800022
ER
PT J
AU Kirshenbaum, A
Desai, A
Bandara, G
Cruse, G
Fischer, E
Gilfillan, AM
Gahl, W
Metcalfe, DD
AF Kirshenbaum, Arnold
Desai, Avanti
Bandara, Geethani
Cruse, Glenn
Fischer, Elizabeth
Gilfillan, Alasdair M.
Gahl, William
Metcalfe, Dean D.
TI Establishment of the Hermansky Pudlak Mastocyte (HPM) Cell Line Which
Has the HPS1 16-Bp Duplication (c.1470_1486dup16)
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology
(AAAAI)
CY FEB 22-26, 2013
CL San Antonio, TX
SP Amer Acad Allergy, Asthma & Immunol (AAAAI)
C1 [Kirshenbaum, Arnold; Desai, Avanti; Bandara, Geethani; Cruse, Glenn; Fischer, Elizabeth; Gilfillan, Alasdair M.; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Gahl, William] NHGRI, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2013
VL 131
IS 2
SU S
BP AB115
EP AB115
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 111WC
UT WOS:000316550800417
ER
PT J
AU Komarow, HD
Waites, C
Young, ML
Nelson, C
Arceo, S
Metcalfe, DD
AF Komarow, Hirsh D.
Waites, Cameron
Young, Michael L.
Nelson, Celeste
Arceo, Sarah
Metcalfe, Dean D.
TI Basophil Activation Following Cold Challenge in Patients with
Cold-Induced Urticaria
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology
(AAAAI)
CY FEB 22-26, 2013
CL San Antonio, TX
SP Amer Acad Allergy, Asthma & Immunol (AAAAI)
C1 [Komarow, Hirsh D.; Waites, Cameron; Nelson, Celeste; Arceo, Sarah; Metcalfe, Dean D.] NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA.
[Young, Michael L.] SAICl Frederick Inc, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2013
VL 131
IS 2
SU S
BP AB119
EP AB119
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 111WC
UT WOS:000316550800430
ER
PT J
AU Lawrence, MG
Siegel, A
DeRavin, SS
Hanson, EP
Moir, S
Klein, C
Holland, SM
Uzel, G
Milner, JD
AF Lawrence, Monica G.
Siegel, Andrea
DeRavin, Suk See
Hanson, Eric Paul
Moir, Susan
Klein, Christoph
Holland, Steven M.
Uzel, Gulbu
Milner, Joshua D.
TI IL-21 Receptor Mutation in Humans Leads to Disseminated
Cryptosporidiosis, Antibody Defects, and Abnormal B and T Cell Function
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology
(AAAAI)
CY FEB 22-26, 2013
CL San Antonio, TX
SP Amer Acad Allergy, Asthma & Immunol (AAAAI)
C1 [Lawrence, Monica G.; Siegel, Andrea; DeRavin, Suk See; Moir, Susan; Holland, Steven M.; Uzel, Gulbu; Milner, Joshua D.] NIAID, Bethesda, MD 20892 USA.
[Hanson, Eric Paul] NIAMSD, Bethesda, MD 20892 USA.
[Klein, Christoph] Hannover Med Sch, Hannover, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2013
VL 131
IS 2
SU S
BP AB328
EP AB328
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 111WC
UT WOS:000316550800851
ER
PT J
AU Magnus, MC
Nafstad, P
Stene, LC
Haberg, SE
London, SJ
Stigum, H
Nystad, W
AF Magnus, Maria C.
Nafstad, Per
Stene, Lars Christian
Haberg, Siri Eldevik
London, Stephanie J.
Stigum, Hein
Nystad, Wenche
TI Maternal Vitamin D Status During Pregnancy and Asthma in the Offspring
Among Participants in the Norwegian Mother and Child Cohort Study
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology
(AAAAI)
CY FEB 22-26, 2013
CL San Antonio, TX
SP Amer Acad Allergy, Asthma & Immunol (AAAAI)
C1 [Magnus, Maria C.; Nafstad, Per; Stene, Lars Christian; Haberg, Siri Eldevik; Stigum, Hein; Nystad, Wenche] Norwegian Inst Publ Hlth, Oslo, Norway.
[Nafstad, Per] Univ Oslo, Oslo, Norway.
[London, Stephanie J.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 10
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2013
VL 131
IS 2
SU S
BP AB128
EP AB128
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 111WC
UT WOS:000316550800460
ER
PT J
AU Mueller, G
Pedersen, L
Lih, F
Glesner, J
Chapman, MD
Tomer, K
London, R
Pomes, A
AF Mueller, Geoffrey
Pedersen, Lars
Lih, Fred
Glesner, Jill
Chapman, Martin D.
Tomer, Ken
London, Robert
Pomes, Anna
TI The Cockroach Allergen Bla g 1 Forms Alpha Helical Capsules with an
Internal Lipid Binding Cavity: Implications for Allergenicity
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology
(AAAAI)
CY FEB 22-26, 2013
CL San Antonio, TX
SP Amer Acad Allergy, Asthma & Immunol (AAAAI)
C1 [Mueller, Geoffrey; Pedersen, Lars; Lih, Fred; Tomer, Ken; London, Robert] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Glesner, Jill; Chapman, Martin D.; Pomes, Anna] Indoor Biotechnol Inc, Charlottesville, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2013
VL 131
IS 2
SU S
BP AB16
EP AB16
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 111WC
UT WOS:000316550800057
ER
PT J
AU Sever, ML
Thomas, J
Calatroni, A
Yeatts, K
Visness, C
Mitchell, H
Zeldin, DC
AF Sever, Michelle L.
Thomas, James
Calatroni, Agustin
Yeatts, Karin
Visness, Cynthia
Mitchell, Herman
Zeldin, Darryl C.
TI Allergen Exposure Influences the Relationship Between Community Violence
and Asthma Morbidity: The Inner City Asthma Study
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology
(AAAAI)
CY FEB 22-26, 2013
CL San Antonio, TX
SP Amer Acad Allergy, Asthma & Immunol (AAAAI)
C1 [Sever, Michelle L.; Zeldin, Darryl C.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Sever, Michelle L.; Thomas, James; Yeatts, Karin] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Calatroni, Agustin; Visness, Cynthia; Mitchell, Herman] Rho Inc, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2013
VL 131
IS 2
SU S
BP AB55
EP AB55
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 111WC
UT WOS:000316550800201
ER
PT J
AU Teng, M
Fitzhugh, DJ
Tran, K
Lockey, RF
Collins, P
AF Teng, Michael
Fitzhugh, David J.
Kim Tran
Lockey, Richard F.
Collins, Peter
TI Functional Characterization of A Cis-Acting Temperature Sensitive
Mutation From A Respiratory Syncytial Virus Vaccine Candidate
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology
(AAAAI)
CY FEB 22-26, 2013
CL San Antonio, TX
SP Amer Acad Allergy, Asthma & Immunol (AAAAI)
C1 [Teng, Michael; Fitzhugh, David J.; Kim Tran; Lockey, Richard F.] Univ S Florida, Morsani Coll Med, Tampa, FL USA.
[Teng, Michael; Collins, Peter] NIAID, Bethesda, MD 20892 USA.
[Lockey, Richard F.] James A Haley Vet Hosp, Tampa, FL 33612 USA.
RI Teng, Michael/I-5006-2012
OI Teng, Michael/0000-0002-0722-3659
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2013
VL 131
IS 2
SU S
BP AB11
EP AB11
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 111WC
UT WOS:000316550800037
ER
PT J
AU Merke, DP
Chen, WY
Morissette, R
Xu, Z
Van Ryzin, C
Sachdev, V
Hannoush, H
Shanbhag, SM
Acevedo, AT
Nishitani, M
Arai, AE
McDonnell, NB
AF Merke, Deborah P.
Chen, Wuyan
Morissette, Rachel
Xu, Zhi
Van Ryzin, Carol
Sachdev, Vandana
Hannoush, Hwaida
Shanbhag, Sujata M.
Acevedo, Ana T.
Nishitani, Miki
Arai, Andrew E.
McDonnell, Nazli B.
TI Tenascin-X Haploinsufficiency Associated with Ehlers-Danlos Syndrome in
Patients with Congenital Adrenal Hyperplasia
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID STEROID 21-HYDROXYLASE DEFICIENCY; HYPERMOBILITY TYPE; GENE; DELETIONS;
MUSCLE; CYP21; MICE
AB Context: The gene for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, CYP21A2, is flanked by the gene encoding tenascin-X (TNXB), a connective tissue extracellular matrix protein that has been linked to both autosomal dominant and autosomal recessive Ehlers-Danlos syndrome (EDS). A contiguous deletion of CYP21A2 and TNXB has been described.
Objective: The objective of the study was to determine the frequency and clinical significance of TNXB haploinsufficiency in CAH patients.
Design, Setting, and Participants: A total of 192 consecutive unrelated CAH patients being seen as part of an observational study at the National Institutes of Health Clinical Center (Bethesda, MD) were prospectively studied during 2006-2010. Patients were evaluated for clinical evidence of EDS, including cardiac evaluation. DNA was analyzed by PCR, multiplex ligation-dependent probe amplification, Southern blot, and TNXB sequencing. Tenascin-X expression was evaluated by Western blot analysis of fibroblasts and immunostaining of the skin. CAH patients with TNXB haploinsufficiency were compared with age-matched CAH patients with normal TNXB (controls). Phenotyping of 7 parents with TNXB haploinsufficiency was performed.
Main Outcome Measures: The frequency of TNXB haploinsufficiency among CAH patients and the frequency of EDS symptomatology among CAH patients with TNXB haploinsufficiency and controls.
Results: TNXB haploinsufficiency, here termed CAH-X syndrome, was present in 7% of CAH patients. Twelve of 91 patients carrying a CYP21A2 deletion (13%) carried a contiguous deletion that extended into TNXB. One patient carried a TNXB premature stop codon. Twelve of 13 patients with CAH-X had EDS clinical features. Patients with CAH-X were more likely than age-matched controls to have joint hypermobility (P < .001), chronic joint pain (P = .003), multiple joint dislocations (P = .004), a structural cardiac valve abnormality by echocardiography (P = .02), and reduced tenascin-X expression by Western blot and immunostaining. A subset of parents had clinical findings.
Conclusions: Clinical evaluation for connective tissue dysplasia should be routinely performed in CAH patients, especially those harboring a CYP21A2 deletion. (J Clin Endocrinol Metab 98: E379-E387, 2013)
C1 [Merke, Deborah P.; Van Ryzin, Carol; Acevedo, Ana T.; Nishitani, Miki] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Sachdev, Vandana; Hannoush, Hwaida; Shanbhag, Sujata M.; Arai, Andrew E.] NHLBI, Bethesda, MD 20892 USA.
[Chen, Wuyan; Morissette, Rachel; Xu, Zhi; McDonnell, Nazli B.] NIA, Baltimore, MD 21224 USA.
RP Merke, DP (reprint author), NIH, Ctr Clin, Bldg 10,CRC,Room 1-2740,10 Ctr Dr,MSC 1932, Bethesda, MD 20892 USA.
EM dmerke@nih.gov
RI Xu, Zhi/I-2546-2012
FU National Institutes of Health Clinical Center; Eunice Kennedy Shriver
National Institute of Child Health and Human Development; National
Heart, Lung, and Blood Institute; National Institute on Aging;
Congenital Adrenal Hyperplasia Research, Education, and Support
Foundation; Diurnal Limited
FX This work was supported by the Intramural Research Programs of the
National Institutes of Health Clinical Center, the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, the
National Heart, Lung, and Blood Institute, and The National Institute on
Aging and, in part, by The Congenital Adrenal Hyperplasia Research,
Education, and Support Foundation.; W.C., R.M., Z.X., C.V.R., V.S.,
H.H., S.M.S., A.T.A., M.N., A.E.A., and N.B.M. have nothing to disclose.
D.P.M. received research funding from Diurnal Limited in 2012.
NR 36
TC 12
Z9 12
U1 0
U2 9
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD FEB
PY 2013
VL 98
IS 2
BP E379
EP E387
DI 10.1210/jc.2012-3148
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 108DE
UT WOS:000316270900025
PM 23284009
ER
PT J
AU Nelson, WL
Moser, RP
Han, PKJ
AF Nelson, Wendy L.
Moser, Richard P.
Han, Paul K. J.
TI Exploring Objective and Subjective Numeracy at a Population Level:
Findings From the 2007 Health Information National Trends Survey (HINTS)
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID BREAST-CANCER RISK; MEDICAL DECISION-MAKING; PRIMARY-CARE; LITERACY;
COMPREHENSION; PERCEPTIONS; SCALE; SKILLS; WOMEN
AB Numeracy is a critical component of decision making in health, and low numeracy may adversely affect risk comprehension, medical treatment, and health outcomes. Health researchers have developed objective and subjective measures of numeracy that potentially could be used for clinical or health research purposes. To examine the association between objective and subjective numeracy at a population level, data were obtained from the 2007 Health Information National Trends Survey, a health communication survey that collects data from a nationally representative sample of the U.S. population. Associations between items from 2 published subjective numeracy measures (STAT-Confidence Scale; Subjective Numeracy Scale) and a single published objective numeracy measure were examined with respect to one another and with respect to sociodemographic characteristics using a multivariate logistic regression model. Controlling for demographic covariates, both subjective numeracy measures were significantly associated with each other (p<.0001) and with objective numeracy (p<.0001). Compared with respondents who regarded themselves as low in subjective numeracy, those who regarded themselves as high in subjective numeracy had significantly higher odds of answering the objective numeracy question correctly (STAT-Confidence Scale OR=1.42, CI [1.07, 1.90]; Subjective Numeracy Scale OR=1.71, CI [1.28, 2.28]). However, the subjective measures performed poorly as diagnostic indicators of objective numeracy. Sensitivity and specificity for the STAT-Confidence Scale and the Subjective Numeracy Scale were 67%/49% and 50%/71%, respectively. More work is needed to elucidate the relation between objective and subjective numeracy, at the conceptual and empirical levels, and to develop more robust measures of subjective numeracy that can better discriminate between individuals with low and high objective numeracy.
C1 [Nelson, Wendy L.; Moser, Richard P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Han, Paul K. J.] Maine Med Ctr, Ctr Outcomes Res & Evaluat, Portland, ME 04102 USA.
RP Nelson, WL (reprint author), NCI, 6130 Execut Blvd,EPN 4064,MSC 7363, Bethesda, MD 20892 USA.
EM nelsonw@mail.nih.gov
OI Han, Paul/0000-0003-0165-1940
NR 43
TC 5
Z9 5
U1 0
U2 14
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 1081-0730
J9 J HEALTH COMMUN
JI J. Health Commun.
PD FEB 1
PY 2013
VL 18
IS 2
BP 192
EP 205
DI 10.1080/10810730.2012.688450
PG 14
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA 109OV
UT WOS:000316378800005
PM 23066837
ER
PT J
AU Persky, S
Sanderson, SC
Koehly, LM
AF Persky, Susan
Sanderson, Saskia C.
Koehly, Laura M.
TI Online Communication About Genetics and Body Weight: Implications for
Health Behavior and Internet-Based Education
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID OBESITY; INFORMATION; FRAMEWORK; RISK
AB Social media, specifically online weight loss message board communities, may become an important conduit for information about genetics and body weight. This information has the capacity to influence individuals as it is naturally encountered online, or it could be strategically disseminated for public health purposes. However, little is known about how the public engages with information that they encounter related to genetic underpinnings of body weight, or how their interpretation of this information shapes health beliefs. The present study examined discussions about genetics and weight in message board communities devoted to discussion of weight loss. Fifty-four online discussions, comprising 505 individual posts from 3 weight-loss themed message boards, were coded using a closed-ended procedure. Individuals who discussed genetics and weight in online message board communities initiated these discussions mainly for personal reasons and primarily cited mass mediasourced information. Genetic causes of weight tended to be endorsed alongside behavioral causes. There was no association between cause endorsements and expressed frustration. These findings help elucidate the effects of naturally encountered information about genetics of weight. They may also have implications for the creation of online evidence-based tools to aid communication about genetic advances in ways that encourage positive dietary and physical activity behavior.
C1 [Persky, Susan; Koehly, Laura M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Sanderson, Saskia C.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA.
RP Persky, S (reprint author), NHGRI, NIH, 31 Ctr Dr,Room B1B54D, Bethesda, MD 20892 USA.
EM perskys@mail.nih.gov
FU Intramural NIH HHS [ZIA HG200383-01]
NR 26
TC 4
Z9 4
U1 1
U2 14
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 1081-0730
J9 J HEALTH COMMUN
JI J. Health Commun.
PD FEB 1
PY 2013
VL 18
IS 2
BP 241
EP 249
DI 10.1080/10810730.2012.727951
PG 9
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA 109OV
UT WOS:000316378800008
PM 23194059
ER
PT J
AU Bashir, ZEH
Latief, N
Belyantseva, IA
Iqbal, F
Riazuddin, SA
Khan, SN
Friedman, TB
Riazuddin, S
Riazuddin, S
AF Bashir, Zil-e-Huma
Latief, Noreen
Belyantseva, Inna A.
Iqbal, Farheena
Riazuddin, Sheikh Amer
Khan, Shaheen N.
Friedman, Thomas B.
Riazuddin, Sheikh
Riazuddin, Saima
TI Phenotypic variability of CLDN14 mutations causing DFNB29 hearing loss
in the Pakistani population
SO JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE CLDN14; claudin 14; DFNB29; mild hearing loss; Pakistan; profound
deafness
ID RECESSIVE DEAFNESS DFNB29; TIGHT-JUNCTION; STRIA VASCULARIS;
INTERCELLULAR-JUNCTIONS; INNER-EAR; PROTEIN; GENE; FREQUENCIES;
OCCLUDIN; FAMILIES
AB Human hereditary deafness at the DFNB29 locus on chromosome 21q22.1 is caused by recessive mutations of CLDN14, encoding claudin 14. This tight junction protein is tetramembrane spanning that localizes to the apical tight junctions of organ of Corti hair cells and in many other tissues. Typically, the DFNB29 phenotype is characterized by prelingual, bilateral, sensorineural hearing loss. The goal of this study was to define the identity and frequency of CLDN14 mutations and associated inner ear phenotypes in a cohort of 800 Pakistani families segregating deafness. Hearing loss in 15 multigenerational families was found to co-segregate with CLDN14-linked STR markers. The sequence of the six exons and regions flanking the introns of CLDN14 in these 15 families revealed five likely pathogenic alleles. Two are novel missense substitutions (p.Ser87Ile and p.Ala94Val), whereas p.Arg81His, p.Val85Asp and p.Met133ArgfsX23 have been reported previously. Haplotype analyses indicate that p.Val85Asp and p.Met133ArgfsX23 are founder mutations. The p.Val85Asp accounts for similar to 67% of the mutant alleles of CLDN14 in our cohort. Combined with the previously reported data, CLDN14 mutations were identified in 18 of 800 Pakistani families (2.25; 95% CI, 1.4-3.5). Hearing loss in the affected individuals homozygous for CLDN14 mutations varied from moderate to profound. This phenotypic variability may be due to environmental factors (for example drug and noise exposure) and/or genetic modifiers. Journal of Human Genetics (2013) 58, 102-108; doi:10.1038/jhg.2012.143; published online 13 December 2012
C1 [Bashir, Zil-e-Huma; Latief, Noreen; Riazuddin, Sheikh Amer; Khan, Shaheen N.; Riazuddin, Saima] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan.
[Belyantseva, Inna A.; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, Rockville, MD USA.
[Iqbal, Farheena] Ctr Appl Mol Biol, Lahore, Pakistan.
[Riazuddin, Sheikh Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Riazuddin, Sheikh] Allama Iqbal Med Coll, Allama Iqbal Med Res Ctr, Lahore, Pakistan.
[Riazuddin, Sheikh] Univ Lahore, Lahore, Pakistan.
[Riazuddin, Saima] Cincinnati Childrens Hosp Med Ctr, Div Pediat Otolaryngol Head & Neck Surg, Cincinnati, OH 45229 USA.
[Riazuddin, Saima] Univ Cincinnati, Coll Med, Dept Otolaryngol, Cincinnati, OH USA.
RP Riazuddin, S (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Pediat Otolaryngol Head & Neck Surg, 3333 Burnet Ave,LocR2-2409,MLC 2018, Cincinnati, OH 45229 USA.
EM saima.riazuddin@cchmc.org
RI Nasim Khan, Shaheen/F-2135-2015
FU Action on Hearing Loss grant; National Institute on Deafness and Other
Communication Disorders (NIDCD/NIH) [R01 DC011803, R01 DC011748]; NIDCD
[DC000039-15]
FX We thank the families for the participation and cooperation, and R
Bhatti and T Kausar for technical assistance and Drs D Drayna, G Nayak
and K Kurima for critiques of the manuscript. This work was also
supported by an Action on Hearing Loss grant and National Institute on
Deafness and Other Communication Disorders (NIDCD/NIH) research grants
R01 DC011803 and R01 DC011748 to SR and intramural funds from NIDCD
DC000039-15 to TBF.
NR 51
TC 5
Z9 6
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1434-5161
J9 J HUM GENET
JI J. Hum. Genet.
PD FEB
PY 2013
VL 58
IS 2
BP 102
EP 108
DI 10.1038/jhg.2012.143
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 112SA
UT WOS:000316612200010
PM 23235333
ER
PT J
AU Thomas, A
Shanbhag, S
Haglund, K
Berman, A
Jakopovic, M
Szabo, E
Arai, A
Schrump, DS
Kwong, KF
Rajan, A
Giaccone, G
AF Thomas, Anish
Shanbhag, Sujata
Haglund, Karl
Berman, Arlene
Jakopovic, Marko
Szabo, Eva
Arai, Andrew
Schrump, David S.
Kwong, King F.
Rajan, Arun
Giaccone, Giuseppe
TI Characterization and Management of Cardiac Involvement of Thymic
Epithelial Tumors
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE Thymic epithelial tumors; Cardiac tumors; Cardiovascular magnetic
resonance imaging
ID MALIGNANT THYMOMA; INVASIVE THYMOMA; INTRACAVAL; NEOPLASMS; HEART
AB Introduction: Although thymic epithelial tumors (TETs) commonly infiltrate mediastinal structures, cardiac involvement is uncommon and has not been systematically studied. The purpose of this study was to describe our single-institution experience of the clinical presentation, treatment, and follow-up of cardiac involvement in patients with TETs.
Methods: A single-institution retrospective review of cardiac involvement among patients with TETs from 2008 to 2012.
Results: The frequency of cardiac involvement was 4%. All five patients with confirmed cardiac disease had left heart involvement. Only one patient was symptomatic. Myocardial invasion was the most common mode of involvement followed by transvenous spread. Surgical resection of the involved area was attempted in three patients: in one, surgery was aborted because of extensive myocardial involvement; in the other two patients, resection was incomplete. Surgery averted a potentially catastrophic hemo-dynamic complication in one patient. However, cardiac tumor recurred in both patients who underwent incomplete resection. One patient underwent radiation therapy resulting in complete regression of an aortic root mass.
Conclusions: This study represents the most comprehensive review of cardiac involvement in patients with TETs. In contrast to previous single-case reports, we found a preponderance of asymptomatic presentation, left heart involvement, and myocardial invasion. Dynamic cardiovascular magnetic resonance imaging should be considered in cases when cardiac involvement is suspected. Although immediate surgical resection is indicated for impending hemo-dynamic compromise, long-term palliation with surgery for myocardial involvement seems poor, especially when complete resection cannot be performed. Radiation therapy should be considered in selected patients.
C1 [Thomas, Anish; Berman, Arlene; Rajan, Arun; Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Shanbhag, Sujata; Arai, Andrew] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA.
[Haglund, Karl] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Jakopovic, Marko] Univ Hosp Ctr Zagreb, Sch Med, Zagreb, Croatia.
[Szabo, Eva] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Schrump, David S.; Kwong, King F.] NCI, Surg Branch, Bethesda, MD 20892 USA.
RP Giaccone, G (reprint author), NCI, Room 12N226,10 Ctr Dr, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
RI Giaccone, Giuseppe/E-8297-2017;
OI Giaccone, Giuseppe/0000-0002-5023-7562; Thomas,
Anish/0000-0003-3293-3115
FU Intramural Research Program of the National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institutes of Health.
NR 15
TC 5
Z9 5
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD FEB
PY 2013
VL 8
IS 2
BP 246
EP 249
DI 10.1097/JTO.0b013e31827bd931
PG 4
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 107HA
UT WOS:000316204900021
PM 23328550
ER
PT J
AU Trask, SD
Boehme, KW
Dermody, TS
Patton, JT
AF Trask, Shane D.
Boehme, Karl W.
Dermody, Terence S.
Patton, John T.
TI Comparative analysis of Reoviridae reverse genetics methods
SO METHODS
LA English
DT Article
DE Reverse genetics systems; Infectious RNA; Recombinant virus; Reoviridae;
Rotavirus; Bluetongue virus; Mammalian reovirus
ID TEMPERATURE-SENSITIVE MUTANTS; BLUETONGUE VIRUS; GENOME REPLICATION;
ROTAVIRUS; RNA; SYSTEM; REARRANGEMENT; GENERATION; SEGMENTS; TRANSCRIPTS
AB Effective methods to engineer the segmented, double-stranded RNA genomes of Reoviridae viruses have only recently been developed. Mammalian orthoreoviruses (MRV) and bluetongue virus (BTV) can be recovered from entirely recombinant reagents, significantly improving the capacity to study the replication, pathogenesis, and transmission of these viruses. Conversely, rotaviruses (RVs), which are the major etiological agent of severe gastroenteritis in infants and children, have thus far only been modified using single-segment replacement methods. Reoviridae reverse genetics techniques universally rely on site-specific initiation of transcription by T7 RNA polymerase to generate the authentic 5' end of recombinant RNA segments, but they vary in how the RNAs are introduced into cells: recombinant BTV is recovered by transfection of in vitro transcribed RNAs, whereas recombinant MRV and RV RNAs are transcribed intra-cellularly from transfected plasmid cDNAs. Additionally, several parameters have been identified in each system that are essential for recombinant virus recovery. Generating recombinant BTV requires the use of 5' capped RNAs and is enhanced by multiple rounds of RNA transfection, suggesting that translation of viral proteins is likely the rate-limiting step. For RV, the efficiency of recovery is almost entirely dependent on the strength of the selection mechanism used to isolate the single-segment recombinant RV from the unmodified helper virus. The reverse genetics methods for BTV and RV are presented and compared to the previously described MRV methods. Analysis and comparison of each method suggest several key lines of research that might lead to a reverse genetics system for RV, analogous to those used for MRV and BTV. Published by Elsevier Inc.
C1 [Trask, Shane D.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Boehme, Karl W.; Dermody, Terence S.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA.
[Boehme, Karl W.; Dermody, Terence S.] Vanderbilt Univ, Sch Med, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN 37232 USA.
[Dermody, Terence S.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.
RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM jpatton@niaid.nih.gov
RI Patton, John/P-1390-2014
FU Intramural Research Program of the National Institutes of Allergy and
Infectious Diseases, National Institutes of Health [Z01 AI000788];
National Institutes of Allergy and Infectious Diseases, National
Institutes of Health [T32 CA09385, F32 AI075776, R01 AI32539, R37
AI38296]; Elizabeth B. Lamb Center for Pediatric Research
FX We thank M. Arnold, M. Morelli, and K. Ogden for careful review of the
manuscript. We thank T. Kobayashi and P. Roy for helpful conversations
and sharing of unpublished data. This work was supported by Public
Health Service award Z01 AI000788 from the Intramural Research Program
of the National Institutes of Allergy and Infectious Diseases, National
Institutes of Health (S.D.T. and J.T.P.), Public Health Service awards
T32 CA09385 (K.W.B.), F32 AI075776 (K.W.B.), R01 AI32539 (T.S.D.), and
R37 AI38296 (T.S.D.) from the National Institutes of Allergy and
Infectious Diseases, National Institutes of Health, and the Elizabeth B.
Lamb Center for Pediatric Research.
NR 49
TC 7
Z9 9
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
J9 METHODS
JI Methods
PD FEB
PY 2013
VL 59
IS 2
BP 199
EP 206
DI 10.1016/j.ymeth.2012.05.012
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 113FE
UT WOS:000316651100005
PM 22687622
ER
PT J
AU Gold, PW
Licinio, J
Pavlatou, MG
AF Gold, P. W.
Licinio, J.
Pavlatou, M. G.
TI Pathological parainflammation and endoplasmic reticulum stress in
depression: potential translational targets through the CNS insulin,
klotho and PPAR-gamma systems
SO MOLECULAR PSYCHIATRY
LA English
DT Review
DE depression; endoplasmic reticulum stress; parainflammation;
translational
ID CORTICOTROPIN-RELEASING HORMONE; C-REACTIVE PROTEIN;
PROLIFERATOR-ACTIVATED RECEPTORS; CENTRAL-NERVOUS-SYSTEM; RAT
CEREBRAL-CORTEX; MAJOR DEPRESSION; HIPPOCAMPAL NEUROGENESIS;
CEREBROSPINAL-FLUID; OXIDATIVE STRESS; SERUM-LEVELS
AB Major depression and bipolar disorder are heterogeneous conditions in which there can be dysregulation of (1) the stress system response, (2) its capacity for counterregulation after danger has passed and (3) the phase in which damaging molecules generated by the stress response are effectively neutralized. The response to stress and depressed mood share common circuitries and mediators, and each sets into motion not only similar affective and cognitive changes, but also similar systemic manifestations. We focus here on two highly interrelated processes, parainflammation and endoplasmic reticulum (ER) stress, each of which can potentially interfere with all phases of a normal stress response in affective illness, including adaptive neuroplastic changes and the ability to generate neural stem cells. Parainflammation is an adaptive response of the innate immune system that occurs in the context of stressors to which we were not exposed during our early evolution, including overfeeding, underactivity, aging, artificial lighting and novel foodstuffs and drugs. We postulate that humans were not exposed through evolution to the current level of acute or chronic social stressors, and hence, that major depressive illness is associated with a parainflammatory state. ER stress refers to a complex program set into motion when the ER is challenged by the production or persistence of more proteins than it can effectively fold. If the ER response is overwhelmed, substantial amounts of calcium are released into the cytoplasm, leading to apoptosis. Parainflammation and ER stress generally occur simultaneously. We discuss three highly interrelated mediators that can effectively decrease parainflammation and ER stress, namely the central insulin, klotho and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) systems and propose that these systems may represent conceptually novel therapeutic targets for the amelioration of the affective, cognitive and systemic manifestations of major depressive disorder. Molecular Psychiatry (2013) 18, 154-165; doi:10.1038/mp.2012.167; published online 27 November 2012
C1 [Gold, P. W.; Pavlatou, M. G.] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Licinio, J.] Australian Natl Univ, John Curtin Sch Med Res, Dept Translat Med, Canberra, ACT 2601, Australia.
RP Gold, PW (reprint author), NIMH, Intramural Res Program, NIH, Room 2D46,10 Ctr Dr, Bethesda, MD 20892 USA.
EM philipgold@mail.nih.gov
RI Licinio, Julio/L-4244-2013
OI Licinio, Julio/0000-0001-6905-5884
NR 156
TC 19
Z9 21
U1 1
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD FEB
PY 2013
VL 18
IS 2
BP 154
EP 165
DI 10.1038/mp.2012.167
PG 12
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 112BW
UT WOS:000316567800007
PM 23183489
ER
PT J
AU Chen, DT
Jiang, X
Akula, N
Shugart, YY
Wendland, JR
Steele, CJM
Kassem, L
Park, JH
Chatterjee, N
Jamain, S
Cheng, A
Leboyer, M
Muglia, P
Schulze, TG
Cichon, S
Nothen, MM
Rietschel, M
McMahon, F
AF Chen, D. T.
Jiang, X.
Akula, N.
Shugart, Y. Y.
Wendland, J. R.
Steele, C. J. M.
Kassem, L.
Park, J-H
Chatterjee, N.
Jamain, S.
Cheng, A.
Leboyer, M.
Muglia, P.
Schulze, T. G.
Cichon, S.
Noethen, M. M.
Rietschel, M.
McMahon, F.
CA BiGS
TI Genome-wide association study meta-analysis of European and
Asian-ancestry samples identifies three novel loci associated with
bipolar disorder
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE ANK3; bipolar disorder; LBA1; meta-analysis; TRANK1; 3p21
ID DEPRESSIVE-DISORDERS; SUSCEPTIBILITY LOCI; EXPRESSION LEVEL; VALPROIC
ACID; TWIN; RISK; REPLICATION; GENETICS; HETEROGENEITY; HERITABILITY
AB Meta-analyses of bipolar disorder (BD) genome-wide association studies (GWAS) have identified several genome-wide significant signals in European-ancestry samples, but so far account for little of the inherited risk. We performed a meta-analysis of similar to 750 000 high-quality genetic markers on a combined sample of similar to 14 000 subjects of European and Asian-ancestry (phase I). The most significant findings were further tested in an extended sample of similar to 17 700 cases and controls (phase II). The results suggest novel association findings near the genes TRANK1 (LBA1), LMAN2L and PTGFR. In phase I, the most significant single nucleotide polymorphism (SNP), rs9834970 near TRANK1, was significant at the P = 2.4 x 10(-11) level, with no heterogeneity. Supportive evidence for prior association findings near ANK3 and a locus on chromosome 3p21.1 was also observed. The phase II results were similar, although the heterogeneity test became significant for several SNPs. On the basis of these results and other established risk loci, we used the method developed by Park et al. to estimate the number, and the effect size distribution, of BD risk loci that could still be found by GWAS methods. We estimate that >63 000 case-control samples would be needed to identify the similar to 105BD risk loci discoverable by GWAS, and that these will together explain <6% of the inherited risk. These results support previous GWAS findings and identify three new candidate genes for BD. Further studies are needed to replicate these findings and may potentially lead to identification of functional variants. Sample size will remain a limiting factor in the discovery of common alleles associated with BD. Molecular Psychiatry (2013) 18, 195-205; doi:10.1038/mp.2011.157; published online 20 December 2011
C1 [Chen, D. T.; Jiang, X.; Akula, N.; Shugart, Y. Y.; Wendland, J. R.; Steele, C. J. M.; Kassem, L.; Schulze, T. G.; McMahon, F.] NIMH, Human Genet Branch, Intramural Res Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Park, J-H; Chatterjee, N.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MA USA.
[Jamain, S.; Leboyer, M.] Univ Paris Est, Grp Hosp Henri Mondor Albert Chenevier, AP HP, Fdn FondaMental,Inserm U955,Dept Psychiat, Creteil, France.
[Cheng, A.] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
[Muglia, P.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[Schulze, T. G.] Univ Gottingen, Univ Med Ctr, Dept Psychiat & Psychotherapy, Sect Psychiat Genet, D-37073 Gottingen, Germany.
[Cichon, S.; Noethen, M. M.] Inst Neurosci & Med, Julich, Germany.
[Cichon, S.; Noethen, M. M.] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany.
[Rietschel, M.] Univ Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-68131 Mannheim, Germany.
RP Chen, DT (reprint author), NIMH, Human Genet Branch, Intramural Res Program, NIH,US Dept Hlth & Human Serv, 35 Convent Dr,Room 1A-208, Bethesda, MD 20892 USA.
EM chend4@mail.nih.gov
RI Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon,
Sven/B-9618-2014; Zhang, Peng/N-2920-2014; Cohen-Woods,
Sarah/F-8674-2014;
OI Jamain, Stephane/0000-0002-4321-4100; Cichon, Sven/0000-0002-9475-086X;
Cichon, Sven/0000-0002-9475-086X; Zhang, Peng/0000-0003-1182-1392;
McMahon, Francis/0000-0002-9469-305X; Craig, Ian/0000-0002-4063-1005;
Cohen-Woods, Sarah/0000-0003-2199-6129; Nothen,
Markus/0000-0002-8770-2464
FU NIMH NIH HHS [R01 MH094483]
NR 69
TC 53
Z9 53
U1 0
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD FEB
PY 2013
VL 18
IS 2
BP 195
EP 205
DI 10.1038/mp.2011.157
PG 11
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 112BW
UT WOS:000316567800012
PM 22182935
ER
PT J
AU Yamaji, D
Kang, K
Robinson, GW
Hennighausen, L
AF Yamaji, Daisuke
Kang, Keunsoo
Robinson, Gertraud W.
Hennighausen, Lothar
TI Sequential activation of genetic programs in mouse mammary epithelium
during pregnancy depends on STAT5A/B concentration
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ALVEOLAR CELL FATE; GROWTH-HORMONE; GLAND DEVELOPMENT; TRANSGENIC MICE;
RNA-SEQ; DIFFERENTIATION; TRANSCRIPTION; EXPRESSION; PROLIFERATION; MILK
AB The transcription factors Signal Transducer and Activator of Transcription (STAT) 5A/B mediate prolactin-induced mammary development during pregnancy. However, it is not clear how the different processes, expansion and maturation of alveolar precursor cells and the differential induction of milk protein genes are regulated on a molecular level. We have used mouse genetics and genome-wide analyses to determine how altering concentrations of STAT5A and STAT5B impacts mammary epithelial development during pregnancy and the regulation of target genes. The presence of only a single Stat5a or Stat5b allele was sufficient for the establishment of histologically undifferentiated alveolar units and two alleles permitted the execution of a differentiation program similar to that found with all four alleles. While one copy of Stat5 induced limited expression of target genes, two copies activated a lactation-like gene signature. Using ChIP-seq analyses on intact tissue under physiological conditions, we found that highly expressed and regulated genes were bound by STAT5 in their promoter proximal regions, whereas upstream binding had minor biological consequences. Remarkably, 80% of the genes bound by STAT5 in vivo were not under STAT5 control. RNA polymerase II intensity was directly proportional to STAT5 concentration only on STAT5 regulated genes providing mechanistic insight by which STAT5 activates mammary specific genes.
C1 [Yamaji, Daisuke; Kang, Keunsoo; Robinson, Gertraud W.; Hennighausen, Lothar] NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20815 USA.
[Hennighausen, Lothar] Dankook Univ, Natl Dept Nanobiomed Sci, Cheonan 330714, Chungnam, South Korea.
[Hennighausen, Lothar] Dankook Univ, WCU Res Ctr Nanobiomed Sci, Cheonan 330714, Chungnam, South Korea.
RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20815 USA.
EM lotharh@mail.nih.gov
FU Intramural Research Program (IRP) of NIDDK, NIH; Intramural Research
Programs (IRP) of NIDDK at the National Institutes of Health (NIH), USA;
World Class University Program, Ministry of Education, Science and
Technology, through the National Research Foundation of Korea, South
Korea [R31-10069]; WCU Research Center, Dankook University
FX This work was supported by the Intramural Research Program (IRP) of
NIDDK, NIH. D.Y.: Experimental design, mouse experiments, RNA-seq and
ChIP-seq experiments, data analysis, writing manuscript; K. K.:
bioinformatics data analysis, writing paper; G. W. R.: experimental
design, mouse experiments, data analysis, writing manuscript; L. H.:
experimental design, data analysis, writing manuscript. We thank Dr.
Harold Smith (NIDDK Genomics core) for sequencing RNA-seq and ChIP-seq
libraries.; The Intramural Research Programs (IRP) of NIDDK at the
National Institutes of Health (NIH), USA. Funding for the open access
charge: the World Class University Program, Ministry of Education,
Science and Technology, through the National Research Foundation of
Korea, South Korea [R31-10069]; WCU Research Center, Dankook University.
NR 47
TC 32
Z9 32
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD FEB
PY 2013
VL 41
IS 3
BP 1622
EP 1636
DI 10.1093/nar/gks1310
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 109FM
UT WOS:000316351800028
PM 23275557
ER
PT J
AU McIntyre, J
Vidal, AE
McLenigan, MP
Bomar, MG
Curti, E
McDonald, JP
Plosky, BS
Ohashi, E
Woodgate, R
AF McIntyre, Justyna
Vidal, Antonio E.
McLenigan, Mary P.
Bomar, Martha G.
Curti, Elena
McDonald, John P.
Plosky, Brian S.
Ohashi, Eiji
Woodgate, Roger
TI Ubiquitin mediates the physical and functional interaction between human
DNA polymerases eta and iota
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID CELL NUCLEAR ANTIGEN; TRANSLESION SYNTHESIS POLYMERASES; PIGMENTOSUM
VARIANT CELLS; C-TERMINAL DOMAIN; XERODERMA-PIGMENTOSUM; STRUCTURAL
BASIS; REPLICATION MACHINERY; CRYSTAL-STRUCTURE; BINDING MOTIFS;
ERROR-PRONE
AB Human DNA polymerases eta and iota are best characterized for their ability to facilitate translesion DNA synthesis (TLS). Both polymerases (pols) co-localize in 'replication factories' in vivo after cells are exposed to ultraviolet light and this co-localization is mediated through a physical interaction between the two TLS pols. We have mapped the pol eta-iota interacting region to their respective ubiquitin-binding domains (UBZ in pol mu and UBM1 and UBM2 in pol iota), and demonstrate that ubiquitination of either TLS polymerase is a prerequisite for their physical and functional interaction. Importantly, while monoubiquitination of pol eta precludes its ability to interact with proliferating cell nuclear antigen (PCNA), it enhances its interaction with poli. Furthermore, a pol iota-ubiquitin chimera interacts avidly with both pol eta and PCNA. Thus, the ubiquitination status of pol eta, or poli plays a key regulatory function in controlling the protein partners with which each polymerase interacts, and in doing so, determines the efficiency of targeting the respective polymerase to stalled replication forks where they facilitate TLS.
C1 [McIntyre, Justyna; Vidal, Antonio E.; McLenigan, Mary P.; Bomar, Martha G.; Curti, Elena; McDonald, John P.; Plosky, Brian S.; Ohashi, Eiji; Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA.
RP Woodgate, R (reprint author), NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA.
EM woodgate@nih.gov
RI McIntyre, Justyna/M-9186-2014
FU National Institute of Child Health and Human Development/National
Institutes of Health Intramural Research Program; Programa Ramon y Cajal
(Ministerio de Ciencia e Innovacion, Spain); NICHD Intramural Research
program
FX The National Institute of Child Health and Human Development/National
Institutes of Health Intramural Research Program (to R. W.); Programa
Ramon y Cajal (Ministerio de Ciencia e Innovacion, Spain) (to A. V.).
Funding for open access charge: NICHD Intramural Research program.
NR 43
TC 9
Z9 9
U1 0
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD FEB
PY 2013
VL 41
IS 3
BP 1649
EP 1660
DI 10.1093/nar/gks1277
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 109FM
UT WOS:000316351800030
PM 23248005
ER
PT J
AU Freudenthal, BD
Beard, WA
Wilson, SH
AF Freudenthal, Bret D.
Beard, William A.
Wilson, Samuel H.
TI DNA polymerase minor groove interactions modulate mutagenic bypass of a
templating 8-oxoguanine lesion
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID OXIDATIVELY DAMAGED DNA; ERROR-FREE REPLICATION; ACTIVE-SITE; NUCLEOTIDE
INSERTION; CRYSTAL-STRUCTURE; KINETIC-ANALYSIS; STRUCTURAL BASIS;
STEADY-STATE; BETA; OPPOSITE
AB A major base lesion resulting from oxidative stress is 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxoG) that has ambiguous coding potential. Error-free DNA synthesis involves 8-oxoG adopting an anti-conformation to base pair with cytosine whereas mutagenic bypass involves 8-oxoG adopting a syn-conformation to base pair with adenine. Left unrepaired the syn-8-oxoG/dAMP base pair results in a G-C to T-A transversion. During base excision repair of this mispair, DNA polymerase (pol) beta is confronted with gap filling opposite 8-oxoG. To determine how pol beta discriminates between anti- and syn-8-oxoG, we introduced a point mutation (R283K) to alter insertion specificity. Kinetic studies demonstrate that this substitution results in an increased fidelity opposite 8-oxoG. Structural studies with R283K pol 13 show that the binary DNA complex has 8-oxoG in equilibrium between anti- and syn-forms. Ternary complexes with incoming dCTP resemble the wild-type enzyme, with templating anti-8-oxoG base pairing with incoming cytosine. In contrast to wild-type pol D, the ternary complex of the R283K mutant with an incoming dATP-analogue and templating 8-oxoG resembles a G-A mismatched structure with 8-oxoG adopting an anti-conformation. These results demonstrate that the incoming nucleotide is unable to induce a syn-8-oxoG conformation without minor groove DNA polymerase interactions that influence templating (anti-/syn-equilibrium) of 8-oxoG while modulating fidelity.
C1 [Freudenthal, Bret D.; Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
FU Division of Intramural Research Program of the National Institutes of
health; National Institute of Environmental Health Sciences; National
Institutes of Health [1U19CA105010]; [Z01-ES050158]; [Z01-ES050159]
FX Research Project Numbers [Z01-ES050158 and Z01-ES050159]; Division of
Intramural Research Program of the National Institutes of health,
National Institute of Environmental Health Sciences and was in
association with the National Institutes of Health [1U19CA105010].
Funding for open access charge: Research Project [Z01-ES050158].
NR 51
TC 17
Z9 17
U1 0
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD FEB
PY 2013
VL 41
IS 3
BP 1848
EP 1858
DI 10.1093/nar/gks1276
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 109FM
UT WOS:000316351800045
PM 23267011
ER
PT J
AU Pavon-Eternod, M
David, A
Dittmar, K
Berglund, P
Pan, T
Bennink, JR
Yewdell, JW
AF Pavon-Eternod, Mariana
David, Alexandre
Dittmar, Kimberly
Berglund, Peter
Pan, Tao
Bennink, Jack R.
Yewdell, Jonathan W.
TI Vaccinia and influenza A viruses select rather than adjust tRNAs to
optimize translation
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID SYNONYMOUS CODON USAGE; EXPRESSION; PROTEIN; BIAS; EFFICIENCY; GENES;
HOST; IMMUNE; CANCER; HIV-1
AB Transfer RNAs (tRNAs) are central to protein synthesis and impact translational speed and fidelity by their abundance. Here we examine the extent to which viruses manipulate tRNA populations to favor translation of their own genes. We study two very different viruses: influenza A virus (IAV), a medium-sized (13 kB genome) RNA virus; and vaccinia virus (VV), a large (200 kB genome) DNA virus. We show that the total cellular tRNA population remains unchanged following viral infection, whereas the polysome-associated tRNA population changes dramatically in a virus-specific manner. The changes in polysome-associated tRNA levels reflect the codon usage of viral genes, suggesting the existence of local tRNA pools optimized for viral translation.
C1 [Pavon-Eternod, Mariana; David, Alexandre; Berglund, Peter; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
[Dittmar, Kimberly; Pan, Tao] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
OI David, Alexandre/0000-0003-3365-1339
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases; National Institutes of Health [DP1 GM105386]
FX Division of Intramural Research, National Institute of Allergy and
Infectious Diseases; National Institutes of Health [DP1 GM105386 to T.
P.]. Funding for open access charge: Division of Intramural Research,
National Institute of Allergy and Infectious Diseases.
NR 37
TC 10
Z9 12
U1 1
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD FEB
PY 2013
VL 41
IS 3
BP 1914
EP 1921
DI 10.1093/nar/gks986
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 109FM
UT WOS:000316351800051
PM 23254333
ER
PT J
AU Becchio, C
Del Giudice, M
Dal Monte, O
Latini-Corazzini, L
Pia, L
AF Becchio, Cristina
Del Giudice, Marco
Dal Monte, Olga
Latini-Corazzini, Luca
Pia, Lorenzo
TI In your place: neuropsychological evidence for altercentric remapping in
embodied perspective taking
SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE
LA English
DT Article
DE perspective taking; unilateral neglect; space representation; social
space; altercentric remapping
ID REPRESENTATIONAL NEGLECT; UNILATERAL NEGLECT; TRANSFORMATIONS;
COGNITION; SPACE
AB Humans are able to mentally adopt the spatial perspective of others and represent the visual world from their point of view. Here, we present neuropsychological evidence that information inaccessible from an egocentric perspective can be accessed from the perspective of another person. Patients affected by left neglect were asked to describe arrays of objects from their own egocentric perspective, from an opposite perspective (disembodied perspective taking), and from the point of view of another person actually seated in front of them (embodied perspective taking). Although disembodied perspective-taking ameliorated neglect severity, there was an even stronger positive effect of embodied perspective-taking: items presented on the left and neglected when reported from the egocentric perspective were instead recovered when patients assumed the perspective of the other. These findings suggest that perspective-taking entails an altercentric remapping of space, i.e. remapping of objects and locations coded with reference to the other person's body.
C1 [Becchio, Cristina; Del Giudice, Marco; Dal Monte, Olga; Latini-Corazzini, Luca; Pia, Lorenzo] Dept Psychol, I-10123 Turin, Italy.
[Becchio, Cristina; Del Giudice, Marco] Ctr Cognit Sci, I-10123 Turin, Italy.
[Becchio, Cristina; Latini-Corazzini, Luca; Pia, Lorenzo] NIT, I-10043 Turin, Italy.
[Becchio, Cristina; Latini-Corazzini, Luca; Pia, Lorenzo] Univ Turin, I-10123 Turin, Italy.
[Dal Monte, Olga] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
[Dal Monte, Olga] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Henry M Jackson Fdn, Rockville, MD USA.
RP Pia, L (reprint author), Univ Turin, Dept Psychol, Via Po 14, I-10123 Turin, Italy.
EM lorenzo.pia@unito.it
RI Del Giudice, Marco/F-7007-2010;
OI Del Giudice, Marco/0000-0001-8526-1573; dal monte,
olga/0000-0002-7823-4769; Becchio, Cristina/0000-0002-6845-0521; Pia,
Lorenzo/0000-0002-0360-3152
FU PRIN [prot. 2007JLKBL9_003]; Regione Piemonte, bando Scienze Umane e
Sociali [4/2006]
FX This research was funded by PRIN (Year 2007, prot. 2007JLKBL9_003) (to
L. P.); the Regione Piemonte, bando Scienze Umane e Sociali 2008, L.R.
n. 4/2006 (to C.B.).
NR 23
TC 10
Z9 10
U1 2
U2 19
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1749-5016
J9 SOC COGN AFFECT NEUR
JI Soc. Cogn. Affect. Neurosci.
PD FEB
PY 2013
VL 8
IS 2
BP 165
EP 170
DI 10.1093/scan/nsr083
PG 6
WC Neurosciences; Psychology; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 110CH
UT WOS:000316419200006
PM 22133561
ER
PT J
AU Wu, H
Mitra, M
McCauley, MJ
Thomas, JA
Rouzina, I
Musier-Forsyth, K
Williams, MC
Gorelick, RJ
AF Wu, Hao
Mitra, Mithun
McCauley, Micah J.
Thomas, James A.
Rouzina, Ioulia
Musier-Forsyth, Karin
Williams, Mark C.
Gorelick, Robert J.
TI Aromatic residue mutations reveal direct correlation between HIV-1
nucleocapsid protein's nucleic acid chaperone activity and retroviral
replication
SO VIRUS RESEARCH
LA English
DT Article
DE HIV-1; Infectivity; Nucleic acid chaperone; Nucleocapsid;
Single-molecule DNA stretching; Zinc finger
ID HUMAN-IMMUNODEFICIENCY-VIRUS; PRIMER BINDING-SITE; PREMATURE REVERSE
TRANSCRIPTION; TIME-RESOLVED FLUORESCENCE; FUSION INHIBITOR T-20;
INTEGRATION IN-VITRO; RNA PACKAGING SIGNAL; PLUS-STRAND TRANSFER;
ZINC-FINGER MOTIFS; STRUCTURAL DETERMINANTS
AB The human immunodeficiency virus type 1 (HIV-1) nucleocapsid (NC) protein plays an essential role in several stages of HIV-1 replication. One important function of HIV-1 NC is to act as a nucleic acid chaperone, in which the protein facilitates nucleic acid rearrangements important for reverse transcription and recombination. NC contains only 55 amino acids, with 15 basic residues and two zinc fingers, each having a single aromatic residue (Phe16 and Trp37). Despite its simple structure, HIV-1 NC appears to have optimal chaperone activity, including the ability to strongly aggregate nucleic acids, destabilize nucleic acid secondary structure, and facilitate rapid nucleic acid annealing. Here we combine single molecule DNA stretching experiments with ensemble solution studies of protein-nucleic acid binding affinity, oligonucleotide annealing, and nucleic acid aggregation to measure the characteristics of wild-type (WT) and aromatic residue mutants of HIV-1 NC that are important for nucleic acid chaperone activity. These in vitro results are compared to in vivo HIV-1 replication for viruses containing the same mutations. This work allows us to directly relate HIV-1 NC structure with its function as a nucleic acid chaperone in vitro and in vivo. We show that replacement of either aromatic residue with another aromatic residue results in a protein that strongly resembles WT NC. In contrast, single amino acid substitutions of either Phel 6Ala or Trp37Ala significantly slow down NC's DNA interaction kinetics, while retaining some helixdestabilization capability. A double Phe16A1a/Trp37Ala substitution further reduces the latter activity. Surprisingly, the ensemble nucleic acid binding, annealing, and aggregation properties are not significantly altered for any mutant except the double aromatic substitution with Ala. Thus, elimination of a single aromatic residue from either zinc finger strongly reduces NC's chaperone activity as determined by single molecule DNA stretching experiments without significantly altering its ensemble-averaged biochemical properties. Importantly, the substitution of aromatic residues with Ala progressively decreases NC's nucleic acid chaperone activity while also progressively inhibiting viral replication. Taken together, these data support the critical role of HIV-1 NC's aromatic residues, and establish a direct and statistically significant correlation between nucleic acid chaperone activity and viral replication. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Wu, Hao; McCauley, Micah J.; Williams, Mark C.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
[Mitra, Mithun; Musier-Forsyth, Karin] Ohio State Univ, Dept Chem & Biochem, Ctr Retrovirus Res, Ctr RNA Biol, Columbus, OH 43210 USA.
[Thomas, James A.; Gorelick, Robert J.] SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Rouzina, Ioulia] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
RP Williams, MC (reprint author), Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
EM mark@neu.edu; gorelicr@mail.nih.gov
RI Mitra, Mithun/A-2133-2015;
OI Williams, Mark C./0000-0003-3219-376X; Thomas, James/0000-0002-2509-490X
FU National Cancer Institute; National Institutes of Health
[HHSN261200800001E, GM072462, GM065056]; National Science Foundation
[MCB-0744456]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN261200800001E with SAIC-Frederick, Inc. (RJG). The content
of this publication does not necessarily reflect the views or policies
of the Department of Health and Human Services, nor does mention of
trade names, commercial products, or organizations imply endorsement by
the U.S. Government. This work was also funded by grants from the
National Institutes of Health (GM072462, MCW; GM065056, KMF) and
National Science Foundation (MCB-0744456, MCW). We wish to thank Donald
G. Johnson, Jeremy Miller, Catherine V. Hixson, and Teresa L. Shatzer
for their assistance with preparing plasmids, expression and
purification of recombinant proteins, and cell culture assistance.
NR 108
TC 18
Z9 18
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD FEB
PY 2013
VL 171
IS 2
SI SI
BP 263
EP 277
PG 15
WC Virology
SC Virology
GA 111JL
UT WOS:000316517500001
PM 22814429
ER
PT J
AU Lyonnais, S
Gorelick, RJ
Heniche-Boukhalfa, F
Bouaziz, S
Parissi, V
Mouscadet, JF
Restle, T
Gatell, JM
Le Cam, E
Mirambeau, G
AF Lyonnais, Sebastien
Gorelick, Robert J.
Heniche-Boukhalfa, Fatima
Bouaziz, Serge
Parissi, Vincent
Mouscadet, Jean-Francois
Restle, Tobias
Maria Gatell, Jose
Le Cam, Eric
Mirambeau, Gilles
TI A protein ballet around the viral genome orchestrated by HIV-1 reverse
transcriptase leads to an architectural switch: From
nucleocapsid-condensed RNA to Vpr-bridged DNA
SO VIRUS RESEARCH
LA English
DT Article
DE HIV-1; Nucleocapsid; Viral protein r; Reverse transcription;
Pre-integration complex; Integrase
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACID CHAPERONE ACTIVITY; CHAIN VARIABLE
FRAGMENTS; INHIBIT EARLY STAGES; C-TERMINAL DOMAIN; ZINC-FINGER; STRAND
TRANSFER; NUCLEIC-ACIDS; IN-VITRO; PREINTEGRATION COMPLEXES
AB HIV-1 reverse transcription is achieved in the newly infected cell before viral DNA (vDNA) nuclear import. Reverse transcriptase (RT) has previously been shown to function as a molecular motor, dismantling the nucleocapsid complex that binds the viral genome as soon as plus-strand DNA synthesis initiates. We first propose a detailed model of this dismantling in close relationship with the sequential conversion from RNA to double-stranded (ds) DNA, focusing on the nucleocapsid protein (NCp7). The HIV-1 DNA-containing pre-integration complex (PIC) resulting from completion of reverse transcription is translocated through the nuclear pore. The PIC nucleoprotein architecture is poorly understood but contains at least two HIV-1 proteins initially from the virion core, namely integrase (IN) and the viral protein r (Vpr). We next present a set of electron micrographs supporting that Vpr behaves as a DNA architectural protein, initiating multiple DNA bridges over more than 500 base pairs (bp). These complexes are shown to interact with NCp7 bound to single-stranded nucleic acid regions that are thought to maintain IN binding during dsDNA synthesis, concurrently with nucleocapsid complex dismantling. This unexpected binding of Vpr conveniently leads to a compacted but filamentous folding of the vDNA that should favor its nuclear import. Finally, nucleocapsid-like aggregates engaged in dsDNA synthesis appear to efficiently bind to F-actin filaments, a property that may be involved in targeting complexes to the nuclear envelope. More generally, this article highlights unique possibilities offered by in vitro reconstitution approaches combined with macromolecular imaging to gain insights into the mechanisms that alter the nucleoprotein architecture of the HIV-1 genome, ultimately enabling its insertion into the nuclear chromatin. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Lyonnais, Sebastien; Maria Gatell, Jose; Mirambeau, Gilles] IDIBAPS, AIDS Res Grp, E-08036 Barcelona, Spain.
[Gorelick, Robert J.] SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Heniche-Boukhalfa, Fatima; Le Cam, Eric] Univ Paris 11, UMR CNRS 8126, F-94805 Villejuif, France.
[Bouaziz, Serge] Univ Paris 05, Lab Cristallog, F-75006 Paris, France.
[Bouaziz, Serge] Univ Paris 05, RMN Biol, UMR CNRS 8015, F-75006 Paris, France.
[Parissi, Vincent] Univ Bordeaux Segalen, Lab Microbiol Fondamentale & Pathogenicite, CNRS UMR5234, Bordeaux, France.
[Mouscadet, Jean-Francois] CNRS, ENS Cachan, LBPA, F-75700 Paris, France.
[Restle, Tobias] Med Univ Lubeck, Inst Mol Med, Ctr Struct & Cell Biol Med CSCM, D-23538 Lubeck, Germany.
[Mirambeau, Gilles] UPMC Sorbonne Univ, Fac Biol, F-75005 Paris, France.
RP Mirambeau, G (reprint author), IDIBAPS, NUCARCHIV Project, AIDS Res Grp, Villaroel 170, E-08036 Barcelona, Spain.
EM gilles.mirambeau@gmail.com
RI bouaziz, serge/C-1401-2014;
OI Lyonnais, Sebastien/0000-0002-3154-8568
FU European Community [237738]; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]; SIDACTION [A02011-2013]; EC
[LSHG-CT-2003-503480]
FX S. L., J.-F.M., S.B., E.L. and G.M. are grateful to ANRS-AC 14.2 for its
funding, paying a special tribute to Pr. Roger Monier f. S.L. and G.M.
are indebted to the European Community's Seventh Framework Program for
the Grant Agreement IEF No. 237738. This project has been funded in part
with federal funds from the National Cancer Institute, National
Institutes of Health, under contract HHSN261200800001E with
SAIC-Frederick, Inc. (RJG). V.P. is grateful to SIDACTION A02011-2013
for its funding. T.R. acknowledges funding by EC-grant
LSHG-CT-2003-503480. G.M. thanks Dr. Kashif Sadiq for a "last minute"
editing of this manuscript. We also wish to thank Donald G. Johnson and
Catherine V. Hixson of the AIDS and Cancer Virus Program for their
assistance in preparing the recombinant nucleocapsid proteins used in
this study.
NR 149
TC 13
Z9 13
U1 0
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD FEB
PY 2013
VL 171
IS 2
SI SI
BP 287
EP 303
DI 10.1016/j.virusres.2012.09:008
PG 17
WC Virology
SC Virology
GA 111JL
UT WOS:000316517500003
PM 23017337
ER
PT J
AU O'Carroll, IP
Soheilian, F
Kamata, A
Nagashima, K
Rein, A
AF O'Carroll, Ina P.
Soheilian, Ferri
Kamata, Anne
Nagashima, Kunio
Rein, Alan
TI Elements in HIV-1 Gag contributing to virus particle assembly
SO VIRUS RESEARCH
LA English
DT Article
DE HIV-1; Gag; Assembly; In vivo; Oligomerization
ID ROUS-SARCOMA-VIRUS; IN-VITRO; HELICAL STRUCTURE; TYPE-1; PROTEIN;
DOMAIN; DIMERIZATION; MYRISTOYLATION; INFECTIVITY; PRECURSOR
AB The Gag polyprotein is the building block of retroviral particles and its expression is sufficient for assembly in cells. In HIV-1, nucleic acid (NA) is required for recombinant Gag molecules to assemble in a defined system in vitro. Experiments performed by Barklis and co-workers suggested that NA contributes to assembly by promoting Gag oligomerization. Gag is composed of four main domains: the matrix (MA), capsid (CA), nucleocapsid (NC), and p6 domains. We have recently shown that the SP1 linker, which lies between the CA and NC domains, assumes a helical structure at high, but not low, concentrations. We suggested that Gag oligomerization mediates assembly via an SP1-dependent conformational switch that exposes new interfaces for assembly.
Although NA is required for assembly in vitro, deletion of NC, the main RNA-binding domain, does not eliminate particle formation in vivo; these particles lack NA. We hypothesized that alternative pathways that lead to Gag oligomerization or an increase in local Gag concentration, namely Gag-membrane or inter-protein interactions, rescue assembly in the absence of NC-RNA binding. We constructed mutants in which either Gag-membrane binding, the Gag dimer interface, or NC-RNA binding are disrupted. None of these mutants disables assembly. However, combined mutations in any two of these three classes render Gag completely unable to form virus-like particles. Thus, it seems, Gag utilizes at least three types of interactions to form oligomers and any two out of the three are sufficient for assembly. (C) 2012 Published by Elsevier B.V.
C1 [O'Carroll, Ina P.; Rein, Alan] NCI, HIV Drug Resistance Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Soheilian, Ferri; Kamata, Anne; Nagashima, Kunio] SAIC Frederick Inc, Adv Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Rein, A (reprint author), NCI, HIV Drug Resistance Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM reina@mail.nih.gov
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research; NIH Intramural AIDS Targeted Antiviral
Program; National Institutes of Health [HHSN26120080001E]
FX We thank Demetria Harvin and Jane Mirro for technical assistance and
Rachael Crist for participation in the project. We thank David Ott and
Robert Gorelick for helpful discussions. This work was supported in part
by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research, in part by the NIH Intramural
AIDS Targeted Antiviral Program, and part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
HHSN26120080001E.
NR 32
TC 17
Z9 17
U1 1
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD FEB
PY 2013
VL 171
IS 2
SI SI
BP 341
EP 345
DI 10.1016/j.virusres.2012.10.016
PG 5
WC Virology
SC Virology
GA 111JL
UT WOS:000316517500007
PM 23099087
ER
PT J
AU Hergott, CB
Mitra, M
Guo, JH
Wu, TY
Miller, JT
Iwatani, Y
Gorelick, RJ
Levin, JG
AF Hergott, Christopher B.
Mitra, Mithun
Guo, Jianhui
Wu, Tiyun
Miller, Jennifer T.
Iwatani, Yasumasa
Gorelick, Robert J.
Levin, Judith G.
TI Zinc finger function of HIV-1 nucleocapsid protein is required for
removal of 5 '-terminal genomic RNA fragments: A paradigm for RNA
removal reactions in HIV-1 reverse transcription
SO VIRUS RESEARCH
LA English
DT Article
DE HIV-1 nucleocapsid protein; Nucleic acid chaperone; Helix destabilizing
activity; 5 '-Terminal genomic RNA fragments; RNase H cleavage; Reverse
transcription
ID ACID-CHAPERONE ACTIVITY; STRONG-STOP DNA; PLUS-STRAND TRANSFER; H
ACTIVITY; IN-VITRO; VIRUS; MECHANISM; INHIBITION; IDENTIFICATION;
REPLICATION
AB During (-) strong-stop DNA [(-) SSDNA] synthesis, RNase H cleavage of genomic viral RNA generates small 5'-terminal RNA fragments (14-18 nt) that remain annealed to the DNA. Unless these fragments are removed, the minus-strand transfer reaction, required for (-) SSDNA elongation, cannot occur. Here, we describe the mechanism of 5'-terminal RNA removal and the roles of HIV-1 nucleocapsid protein (NC) and RNase H cleavage in this process. Using an NC-dependent system that models minus-strand transfer, we show that the presence of short terminal fragments pre-annealed to (-) SSDNA has no impact on strand transfer, implying efficient fragment removal. Moreover, in reactions with an RNase H- reverse transcriptase mutant, NC alone is able to facilitate fragment removal, albeit less efficiently than in the presence of both RNase H activity and NC. Results obtained from novel electrophoretic gel mobility shift and Forster Resonance Energy Transfer assays, which each directly measure RNA fragment release from a duplex in the absence of DNA synthesis, demonstrate for the first time that the architectural integrity of NC's zinc finger (ZF) domains is absolutely required for this reaction. This suggests that NC's helix destabilizing activity (associated with the ZFs) facilitates strand exchange through the displacement of these short terminal RNAs by the longer 3' acceptor RNA, which forms a more stable duplex with (-) SSDNA. Taken together with previously published results, we conclude that NC-mediated fragment removal is linked mechanistically with selection of the correct primer for plus-strand DNA synthesis and tRNA removal step prior to plus-strand transfer. Thus, HIV-1 has evolved a single mechanism for these RNA removal reactions that are critical for successful reverse transcription. Published by Elsevier B.V.
C1 [Hergott, Christopher B.; Mitra, Mithun; Guo, Jianhui; Wu, Tiyun; Iwatani, Yasumasa; Levin, Judith G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Viral Gene Regulat, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Miller, Jennifer T.] NCI, Reverse Transcriptase Biochem Sect, HIV Drug Resistance Program, NIH,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Gorelick, Robert J.] SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Levin, JG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Viral Gene Regulat, Program Genom Differentiat, NIH, Bldg 6B,Room 216,6 Ctr Dr, Bethesda, MD 20892 USA.
EM levinju@mail.nih.gov
RI Mitra, Mithun/A-2133-2015
FU Intramural Research Program at the National Institutes of Health (Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; National Cancer Institute; Frederick National Laboratory
for Cancer Research; National Institutes of Health [HHSN261200800001E]
FX We thank Donald G. Johnson and Catherine V. Hixson for their valuable
assistance with the production and purification of the recombinant NC
proteins and Dr. Stuart Le Grice for RNase H- RT. This work
was supported in part by the Intramural Research Program at the National
Institutes of Health (Eunice Kennedy Shriver National Institute of Child
Health and Human Development (C.B.H., M.M., J.G., T.W., Y.I., J.G.L.)
and the National Cancer Institute, Frederick National Laboratory for
Cancer Research (J.T.M.)). This project has also been funded in whole or
in part with federal funds from the Frederick National Laboratory for
Cancer Research, National Institutes of Health, under contract
HHSN261200800001E with SAIC-Frederick, Inc. (R.J.G.). The content of
this publication does not necessarily reflect the views or policies of
the Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government.
NR 59
TC 6
Z9 6
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD FEB
PY 2013
VL 171
IS 2
SI SI
BP 346
EP 355
DI 10.1016/j.virusres.2012.08.013
PG 10
WC Virology
SC Virology
GA 111JL
UT WOS:000316517500008
PM 23149014
ER
PT J
AU Levin, JG
AF Levin, Judith G.
TI Jianhui Guo 1959-2012 Obituary
SO VIRUS RESEARCH
LA English
DT Biographical-Item
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Viral Gene Regulat, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
RP Levin, JG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Viral Gene Regulat, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM levinju@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD FEB
PY 2013
VL 171
IS 2
SI SI
BP 356
EP 356
DI 10.1016/j.virusres.2012.11.001
PG 1
WC Virology
SC Virology
GA 111JL
UT WOS:000316517500009
PM 23414628
ER
PT J
AU Chen, CY
Liu, X
Boris-Lawrie, K
Sharma, A
Jeang, KT
AF Chen, Chia-Yen
Liu, Xiang
Boris-Lawrie, Kathleen
Sharma, Amit
Jeang, Kuan-Teh
TI Cellular RNA helicases and HIV-1: Insights from genome-wide, proteomic,
and molecular studies
SO VIRUS RESEARCH
LA English
DT Article
DE RNA helicases; Human immunodeficiency virus type 1; (HIV-1); DEAD-Box
domain; Antiviral
ID VIRUS TYPE-1 REPLICATION; DEAD-BOX PROTEINS; RIG-I; MICRORNA EXPRESSION;
VIRAL REPLICATION; SILENCING PATHWAY; MOV10 PROTEIN; REV FUNCTION;
HUMAN-CELLS; BINDING
AB RNA helicases are ubiquitous in plants and animals and function in many cellular processes. Retroviruses, such as human immunodeficiency virus (HIV-1), encode no RNA helicases in their genomes and utilize host cellular RNA helicases at various stages of their life cycle. Here, we briefly summarize the roles RNA helicases play in HIV-1 replication that have been identified recently, in part, through genome-wide screenings, proteomics, and molecular studies. Some of these helicases augment virus propagation while others apparently participate in antiviral defenses against viral replication. Published by Elsevier B.V.
C1 [Chen, Chia-Yen; Liu, Xiang; Jeang, Kuan-Teh] NIAID, Mol Virol Sect 1, Lab Mol, NIH, Bethesda, MD 20892 USA.
[Boris-Lawrie, Kathleen; Sharma, Amit] Ohio State Univ, Dept Vet Biosci, Ctr Retrovirus Res, Columbus, OH 43210 USA.
RP Jeang, KT (reprint author), 9000 Rockville Pike,Bldg 4,Room 303, Bethesda, MD 20892 USA.
EM kjeang@niaid.nih.gov
RI Liu, Xiang/F-5731-2014
FU NIAID, NIH, USA; NCI, NIH [P30CA100730, R01CA108882]; IATAP program from
the office of the Director, NIH
FX Research in KTJ's laboratory is supported by intramural funds from
NIAID, NIH, USA; and by the IATAP program from the office of the
Director, NIH. Research in KBL's laboratory is supported by grants
P30CA100730 and R01CA108882 from NCI, NIH.
NR 92
TC 4
Z9 4
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
EI 1872-7492
J9 VIRUS RES
JI Virus Res.
PD FEB
PY 2013
VL 171
IS 2
SI SI
BP 357
EP 365
DI 10.1016/j.virusres.2012.06.022
PG 9
WC Virology
SC Virology
GA 111JL
UT WOS:000316517500010
PM 22814432
ER
PT J
AU Rajagopalan, S
Long, EO
AF Rajagopalan, Sumati
Long, Eric O.
TI A positive role for senescence in reproduction?
SO AGING-US
LA English
DT Editorial Material
ID NATURAL-KILLER-CELLS; CELLULAR SENESCENCE
C1 [Rajagopalan, Sumati; Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Rajagopalan, S (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM sumi@nih.gov; eLong@nih.gov
RI Long, Eric/G-5475-2011
OI Long, Eric/0000-0002-7793-3728
NR 8
TC 2
Z9 2
U1 0
U2 0
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD FEB
PY 2013
VL 5
IS 2
BP 96
EP 97
PG 2
WC Cell Biology
SC Cell Biology
GA 104HL
UT WOS:000315982700002
PM 23518705
ER
PT J
AU Saini, N
Zhang, Y
Usdin, K
Lobachev, KS
AF Saini, Natalie
Zhang, Yu
Usdin, Karen
Lobachev, Kirill S.
TI When secondary comes first - The importance of non-canonical DNA
structures
SO BIOCHIMIE
LA English
DT Review
DE Triplex; G-quartet; Hairpin; Cruciform; Holliday junction; RNA:DNA
hybrid; Replication transcription collision
ID G-QUADRUPLEXES; DISEASE
AB Secondary structure-forming DNA motifs have achieved infamy because of their association with a variety of human diseases and cancer. The 3rd FASEB summer conference on dynamic DNA structures focused on the mechanisms responsible for the instabilities inherent to repetitive DNA and presented many exciting and novel aspects related to the metabolism of secondary structures. In addition, the meeting encompassed talks and posters on the dynamic structures that are generated during DNA metabolism including nicked DNA, Holliday junctions and RNA:DNA hybrids. New approaches for analysis and sequencing technologies put forth secondary structures and other DNA intermediates as vital regulators of a variety of cellular processes that contribute to evolution, polymorphisms and diseases. (c) 2012 Elsevier Masson SAS. All rights reserved.
C1 [Saini, Natalie; Zhang, Yu; Lobachev, Kirill S.] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA.
[Saini, Natalie; Zhang, Yu; Lobachev, Kirill S.] Georgia Inst Technol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA.
[Usdin, Karen] NIDDKD, Sect Gene Struct & Dis, NIH, Bethesda, MD 20892 USA.
RP Lobachev, KS (reprint author), Georgia Inst Technol, Sch Biol, 310 Ferst Dr, Atlanta, GA 30332 USA.
EM kirill.lobachev@biology.gatech.edu
FU NSF [MCB-0818122]; NIH [R01GM082950]
FX We are grateful to all the participants at the meeting who agreed to
present unpublished results in this review. On behalf of the organizers,
we would also like to thank ABCAM, American Society for Biochemistry and
Molecular Biology, Annual Reviews, Elsevier, New England Biolabs, Inc.,
Public Library of Science and Tufts University, School of Arts and
Sciences for their generous support for the meeting. The studies in KL
laboratory were supported by the grants MCB-0818122 from NSF and
R01GM082950 from NIH.
NR 10
TC 10
Z9 12
U1 3
U2 38
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0300-9084
J9 BIOCHIMIE
JI Biochimie
PD FEB
PY 2013
VL 95
IS 2
BP 117
EP 123
DI 10.1016/j.biochi.2012.10.005
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 099IH
UT WOS:000315614200001
PM 23084930
ER
PT J
AU Perez, EA
Press, MF
Dueck, AC
Jenkins, RB
Kim, C
Chen, BY
Villalobos, I
Paik, S
Buyse, M
Wiktor, AE
Meyer, R
Finnigan, M
Zujewski, J
Shing, M
Stern, HM
Lingle, WL
Reinholz, MM
Slamon, DJ
AF Perez, Edith A.
Press, Michael F.
Dueck, Amylou C.
Jenkins, Robert B.
Kim, Chungyeul
Chen, Beiyun
Villalobos, Ivonne
Paik, Soonmyung
Buyse, Marc
Wiktor, Anne E.
Meyer, Reid
Finnigan, Melanie
Zujewski, JoAnne
Shing, Mona
Stern, Howard M.
Lingle, Wilma L.
Reinholz, Monica M.
Slamon, Dennis J.
TI Immunohistochemistry and fluorescence in situ hybridization assessment
of HER2 in clinical trials of adjuvant therapy for breast cancer (NCCTG
N9831, BCIRG 006, and BCIRG 005)
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; HER2 testing; FISH; IHC; Concordance
ID HER-2/NEU GENE AMPLIFICATION; INTRATUMORAL HETEROGENEITY; CHROMOSOME-17;
TRASTUZUMAB; CARCINOMAS; GUIDELINES; SPECIMENS; ONCOGENE
AB A comprehensive, blinded, pathology evaluation of HER2 testing in HER2-positive/negative breast cancers was performed among three central laboratories. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analyses were performed on 389 tumor blocks from three large adjuvant trials: N9831, BCIRG-006, and BCIRG-005. In 123 cases, multiple blocks were examined. HER2 status was defined according to FDA-approved guidelines and was independently re-assessed at each site. Discordant cases were adjudicated at an on-site, face-to-face meeting. Results across three independent pathologists were concordant by IHC in 351/381 (92 %) and FISH in 343/373 (92 %) blocks. Upon adjudication, consensus was reached on 16/30 and 18/30 of discordant IHC and FISH cases, respectively, resulting in overall concordance rates of 96 and 97 %. Among 155 HER2-negative blocks, HER2 status was confirmed in 153 (99 %). In the subset of 102 HER2-positive patients from N9831/BCIRG-006, primary blocks from discordant cases were selected, especially those with discordant test between local and central laboratories. HER2 status was confirmed in 73 (72 %) of these cases. Among 118 and 113 cases with IHC and FISH results and > 1 block evaluable, block-to-block variability/heterogeneity in HER2 results was seen in 10 and 5 %, respectively. IHC-/FISH- was confirmed for 57/59 (97 %) primary blocks from N9831 (locally positive, but centrally negative); however, 5/22 (23 %) secondary blocks showed HER2 positivity. Among 53 N9831 patients with HER2-normal disease adjudicated as IHC-/FISH-(although locally positive), there was a non-statistically significant improvement in disease-free survival with concurrent trastuzumab compared to chemotherapy alone (adjusted hazard ratio 0.34; 95 % CI, 0.11-1.05; p = 0.06). There were similar agreements for IHC and FISH among pathologists (92 % each). Agreement was improved at adjudication (96 %). HER2 tumor heterogeneity appears to partially explain discordant results in cases initially tested as positive and subsequently called negative.
C1 [Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA.
[Press, Michael F.; Villalobos, Ivonne] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Dueck, Amylou C.] Mayo Clin, Scottsdale, AZ 85259 USA.
[Jenkins, Robert B.; Chen, Beiyun; Wiktor, Anne E.; Meyer, Reid; Lingle, Wilma L.; Reinholz, Monica M.] Mayo Clin, Rochester, MN 55905 USA.
[Kim, Chungyeul; Paik, Soonmyung; Finnigan, Melanie] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA.
[Buyse, Marc] IDDI, B-1340 Louvain, Belgium.
[Zujewski, JoAnne] NCI, Bethesda, MD 20892 USA.
[Shing, Mona; Stern, Howard M.] Genentech Inc, San Francisco, CA 94080 USA.
[Slamon, Dennis J.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
RP Perez, EA (reprint author), Mayo Clin, 4500 San Pablo Rd S, Jacksonville, FL 32224 USA.
EM perez.edith@mayo.edu
OI kim, chungyeul/0000-0002-9636-5228
FU Genentech; GSK; NIH/NCI; Breast Cancer Research Foundation; Ventana
FX Dr. Perez receives research funding from Genentech, GSK, NIH/NCI, and
the Breast Cancer Research Foundation. Dr. Paik receives funding from
GSK. Dr. Press is a consultant for Genentech, Ventana, Roche,
GlaxoSmithKline, and Halozyme. He also receives research funding from
Ventana. Dr. Slamon is a consultant for Genentech and Sanofi-Aventis.
Dr. Shing receives remuneration for employment at Genentech Inc. Dr.
Stern receives remuneration for employment at Genentech Research and
Early Development. He also has stock ownership in Roche Holding AG. All
other authors declare that they have no conflicts of interest.
NR 29
TC 39
Z9 40
U1 1
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD FEB
PY 2013
VL 138
IS 1
BP 99
EP 108
DI 10.1007/s10549-013-2444-y
PG 10
WC Oncology
SC Oncology
GA 099CX
UT WOS:000315598200010
PM 23420271
ER
PT J
AU Helenius, A
Moss, B
AF Helenius, Ari
Moss, Bernard
TI Virus entry - an unwilling collaboration by the cell Editorial overview
SO CURRENT OPINION IN VIROLOGY
LA English
DT Editorial Material
C1 [Helenius, Ari] ETH, Inst Biochem, CH-8093 Zurich, Switzerland.
[Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Helenius, A (reprint author), ETH, Inst Biochem, HPM E 6-3,Schafmattstr 18, CH-8093 Zurich, Switzerland.
EM ari.helenius@bc.biol.ethz.ch; bmoss@nih.gov
FU Intramural NIH HHS [ZIA AI000539-26]
NR 0
TC 3
Z9 3
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1879-6257
J9 CURR OPIN VIROL
JI Curr. Opin. Virol.
PD FEB
PY 2013
VL 3
IS 1
BP 1
EP 2
DI 10.1016/j.coviro.2013.01.003
PG 2
WC Virology
SC Virology
GA 101FE
UT WOS:000315759800001
PM 23395460
ER
PT J
AU Pierson, TC
Kielian, M
AF Pierson, Theodore C.
Kielian, Margaret
TI Flaviviruses: braking the entering
SO CURRENT OPINION IN VIROLOGY
LA English
DT Article
ID BORNE ENCEPHALITIS-VIRUS; WEST-NILE-VIRUS; HUMAN DENDRITIC CELLS;
ENVELOPE PROTEIN-E; DENGUE-VIRUS; MEMBRANE-FUSION; INFECTIOUS ENTRY;
HEPARAN-SULFATE; DC-SIGN; ANTIVIRAL COMPOUNDS
AB Flaviviruses are small spherical virus particles covered by a dense icosahedral array of envelope (E) proteins that mediate virus attachment to cells and the fusion of viral and cellular membranes. Our understanding of the mechanism by which flavivirus E proteins orchestrate entry into cells has been advanced by studies of E structure and arrangement on the virion at different steps of the virus entry/membrane fusion process. When combined with an increasingly clear (albeit still incomplete) view of the cell biology of virus entry, these advances suggest new antiviral strategies. Indeed, inhibitors that target cellular and viral processes involved in entry show promise as powerful tools to study this critical step of the viral lifecycle, and with luck, may ultimately lead to therapeutic advances.
C1 [Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, NIH, Bethesda, MD 20892 USA.
[Kielian, Margaret] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA.
RP Pierson, TC (reprint author), NIAID, Viral Pathogenesis Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM piersontc@mail.nih.gov
FU intramural program of the National Institute of Allergy and Infectious
Disease; National Institutes of Health [GM057454, AI075647,
U54AI057158-Lipkin]
FX Work in the authors' laboratories was supported by the intramural
program of the National Institute of Allergy and Infectious Disease
(TCP), and by National Institutes of Health grants GM057454, AI075647,
and U54AI057158-Lipkin (MK). The authors wish to thank Dr. Heather
Hickman and members of our laboratories for critical evaluation of this
review. We would like to thank Ethan Tyler (NIH/OD) and Phong Lee
(NIAID, NIH) for assistance with preparation of the figures. We
acknowledge the important contributions of those researchers whose work
was not fully cited due to space limitations.
NR 86
TC 37
Z9 39
U1 3
U2 33
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1879-6257
J9 CURR OPIN VIROL
JI Curr. Opin. Virol.
PD FEB
PY 2013
VL 3
IS 1
BP 3
EP 12
DI 10.1016/j.coviro.2012.12.001
PG 10
WC Virology
SC Virology
GA 101FE
UT WOS:000315759800002
PM 23352692
ER
PT J
AU Mendola, P
Brett, K
DiBari, JN
Pollack, AZ
Tandon, R
Shenassa, ED
AF Mendola, Pauline
Brett, Kate
DiBari, Jessica N.
Pollack, Anna Z.
Tandon, Rashmi
Shenassa, Edmond D.
TI Menopause and lead body burden among US women aged 45-55, NHANES
1999-2010
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE Lead; Menopause; Women's health; Epidemiology; Environment
ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH;
FOLLICLE-STIMULATING-HORMONE; POSTMENOPAUSAL WOMEN; REPRODUCTIVE
HORMONES; LUTEINIZING-HORMONE; MENSTRUAL CYCLES; BONE; TRANSITION; GIRLS
AB Background: Environmental factors in menopause have received limited attention. Lead is a known reproductive toxicant associated with delayed puberty in girls that may also affect menopause.
Methods: The odds of menopause among US women aged 45-55 were estimated in the National Health and Nutrition Examination Survey, 1999-2010, in relation to quartiles of blood lead. Women still menstruating (n=2158) were compared to women with natural menopause (n=1063). Logistic regression models included age, race/ethnicity, current hormone use, poverty, smoking and where available, bone density or bone alkaline phosphatase.
Results: Lead levels (ug/dL) were higher in menopausal women, geometric mean (standard error)=1.71 (0.04) vs. 1.23 (0.02). Adjusted odds of menopause and 95% confidence intervals for lead quartiles (lowest quartile referent) were 1.7 (1.0-2.8), 2.1 (1.2-3.6), and 4.2 (2.5-7.0) respectively. Results adjusting for bone markers were generally similar but had less precision.
Conclusions: Blood lead was associated with natural menopause in US women even after adjustment for bone turnover. This raises concern that lead exposure, even at low levels, may shorten women's reproductive lifespan. Published by Elsevier Inc.
C1 [Mendola, Pauline; Pollack, Anna Z.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Rockville, MD 20852 USA.
[Brett, Kate; Tandon, Rashmi] CDC, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
[DiBari, Jessica N.; Shenassa, Edmond D.] Univ Maryland, Dept Family Sci, Sch Publ Hlth, Maternal & Child Hlth Program, College Pk, MD 20742 USA.
RP Mendola, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM pauline.mendola@nih.gov
OI Pollack, Anna/0000-0002-4313-3298; Mendola, Pauline/0000-0001-5330-2844
FU Intramural Research Program of the NIH; Eunice Kennedy Shriver National
Institute of Child Health and Human Development
FX This research was supported in part by the Intramural Research Program
of the NIH, Eunice Kennedy Shriver National Institute of Child Health
and Human Development.
NR 25
TC 6
Z9 6
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 0013-9351
J9 ENVIRON RES
JI Environ. Res.
PD FEB
PY 2013
VL 121
BP 110
EP 113
DI 10.1016/j.envres.2012.12.009
PG 4
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 101CV
UT WOS:000315753700015
PM 23352036
ER
PT J
AU Fujiwara, K
Allison, RD
Wang, RY
Bare, P
Matsuura, K
Schechterly, C
Murthy, K
Marincola, FM
Alter, HJ
AF Fujiwara, Kei
Allison, Robert D.
Wang, Richard Y.
Bare, Patricia
Matsuura, Kentaro
Schechterly, Cathy
Murthy, Krishna
Marincola, Francesco M.
Alter, Harvey J.
TI Investigation of Residual Hepatitis C Virus in Presumed Recovered
Subjects
SO HEPATOLOGY
LA English
DT Article
ID SUSTAINED VIROLOGICAL RESPONSE; BLOOD MONONUCLEAR-CELLS; HCV-INFECTED
PATIENTS; PERIPHERAL-BLOOD; ANTIVIRAL THERAPY; REPLICATION; PERSISTENCE;
DONORS; RNA; REEMERGENCE
AB Recent studies have found hepatitis C virus (HCV) RNA in peripheral blood mononuclear cells (PBMCs) of the majority of presumed recovered subjects. We investigated this unexpected finding using samples from patients whose HCV RNA and anti-HCV status had been serially confirmed. HCV RNA was detected in PBMCs from 66 of 67 chronic HCV carriers. Subpopulation analysis revealed that the viral load (log copies/10(6) cells) in B cells (4.14 +/- 0.71) was higher than in total PBMCs (3.62 +/- 0.71; P < 0.05), T cells (1.67 +/- 0.88; P < 0.05), and non-B/T cells (2.48 +/- 1.15; P < 0.05). HCV negative-strand RNA was not detected in PBMCs from any of 25 chronically infected patients. No residual viral RNA was detected in total PBMCs or plasma of 59 presumed recovered subjects (11 spontaneous and 48 treatment induced) using nested real-time polymerase chain reaction with a detection limit of 2 copies/mu g RNA (from similar to 1 x 10(6) cells). PBMCs from 2 healthy HCV-negative blood donors became HCV RNA positive, with B-cell predominance, when mixed in vitro with HCV RNA-positive plasma, thus passively mimicking cells from chronic HCV carriers. No residual HCV was detected in liver or other tissues from 2 spontaneously recovered chimpanzees. Conclusion: (1) HCV RNA was detected in PBMCs of most chronic HCV carriers and was predominant in the B-cell subpopulation; (2) HCV detected in PBMCs was in a nonreplicative form; (3) HCV passively adsorbed to PBMCs of healthy controls in vitro, becoming indistinguishable from PBMCs of chronic HCV carriers; and (4) residual HCV was not detected in plasma or PBMCs of any spontaneous or treatment-recovered subjects or in chimpanzee liver, suggesting that the classic pattern of recovery from HCV infection is generally equivalent to viral eradication. (HEPATOLOGY 2013;57:483-491)
C1 [Fujiwara, Kei; Allison, Robert D.; Wang, Richard Y.; Bare, Patricia; Schechterly, Cathy; Marincola, Francesco M.; Alter, Harvey J.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Matsuura, Kentaro] Nagoya City Univ, Dept Gastroenterol & Metab, Nagoya, Aichi, Japan.
[Murthy, Krishna] Texas Biomed Res Inst, San Antonio, TX USA.
[Fujiwara, Kei] Nagoya Daini Red Cross Hosp, Dept Gastroenterol & Hepatol, Nagoya, Aichi, Japan.
[Allison, Robert D.] USN, San Diego, CA 92152 USA.
[Bare, Patricia] Acad Nacl Med Buenos Aires, Inst Invest Hematol, Buenos Aires, DF, Argentina.
RP Alter, HJ (reprint author), NIH, Dept Transfus Med, Bldg 10,Room 1C-711,10 Ctr Dr, Bethesda, MD 20892 USA.
EM HAlter@cc.nih.gov
OI Allison, Robert/0000-0001-8458-5250
FU Intramural Research Program of the Warren G. Magnuson Clinical Center,
National Institutes of Health; Hepatitis Virus Research Foundation of
Japan
FX This research was supported by the Intramural Research Program of the
Warren G. Magnuson Clinical Center, National Institutes of Health. K.F.
was supported by the Hepatitis Virus Research Foundation of Japan
NR 33
TC 20
Z9 20
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD FEB
PY 2013
VL 57
IS 2
BP 483
EP 491
DI 10.1002/hep.25921
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 099TA
UT WOS:000315643400009
PM 22729600
ER
PT J
AU Vickers, KC
Shoucri, BM
Levin, MG
Wu, H
Pearson, DS
Osei-Hwedieh, D
Collins, FS
Remaley, AT
Sethupathy, P
AF Vickers, Kasey C.
Shoucri, Bassem M.
Levin, Michael G.
Wu, Han
Pearson, Daniel S.
Osei-Hwedieh, David
Collins, Francis S.
Remaley, Alan T.
Sethupathy, Praveen
TI MicroRNA-27b Is a Regulatory Hub in Lipid Metabolism and Is Altered in
Dyslipidemia
SO HEPATOLOGY
LA English
DT Article
ID CHOLESTEROL HOMEOSTASIS; HEART-DISEASE; SMALL RNAS; IN-VIVO; PROTEIN;
IDENTIFICATION; EXPRESSION; GENES; LIVER; MICE
AB Cellular and plasma lipid levels are tightly controlled by complex gene regulatory mechanisms. Elevated plasma lipid content, or hyperlipidemia, is a significant risk factor for cardiovascular morbidity and mortality. MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression and have emerged as important modulators of lipid homeostasis, but the extent of their role has not been systematically investigated. In this study we performed high-throughput small RNA sequencing and detected approximate to 150 miRNAs in mouse liver. We then employed an unbiased, in silico strategy to identify miRNA regulatory hubs in lipid metabolism, and miR-27b was identified as the strongest such hub in human and mouse liver. In addition, hepatic miR-27b levels were determined to be sensitive to plasma hyperlipidemia, as evidenced by its approximate to 3-fold up-regulation in the liver of mice on a highfat diet (42% calories from fat). Further, we showed in a human hepatocyte cell line (Huh7) that miR-27b regulates the expression (messenger RNA [mRNA] and protein) of several key lipid-metabolism genes, including Angptl3 and Gpam. Finally, we demonstrated that hepatic miR-27b and its target genes are inversely altered in a mouse model of dyslipidemia and atherosclerosis. Conclusion: miR-27b is responsive to lipid levels and controls multiple genes critical to dyslipidemia. (HEPATOLOGY 2013;57:533-542)
C1 [Vickers, Kasey C.; Shoucri, Bassem M.; Levin, Michael G.; Osei-Hwedieh, David; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, NIH, Bethesda, MD 20892 USA.
[Wu, Han] NHLBI, DNA Sequencing & Computat Biol Core, NIH, Bethesda, MD 20892 USA.
[Pearson, Daniel S.; Collins, Francis S.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Sethupathy, Praveen] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Sethupathy, Praveen] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
RP Sethupathy, P (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
EM praveen_sethupathy@med.unc.edu
RI Wu, Han/E-3455-2013
OI Wu, Han/0000-0002-3972-698X
FU National Human Genome Research Institute (NHGRI); National Heart, Lung,
and Blood Institute (NHLBI) [HL113039-01]; National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) [4R00DK091318-02]
FX Supported by the intramural programs of the National Human Genome
Research Institute (NHGRI) and the National Heart, Lung, and Blood
Institute (NHLBI), a K22 grant HL113039-01 (to K.C.V.) from the NHLBI,
and an R00 grant 4R00DK091318-02 (to P.S.) from the National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK).
NR 55
TC 71
Z9 73
U1 0
U2 29
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD FEB
PY 2013
VL 57
IS 2
BP 533
EP 542
DI 10.1002/hep.25846
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 099TA
UT WOS:000315643400014
PM 22777896
ER
PT J
AU Tsuda, M
Zhang, WC
Yang, GX
Tsuneyama, K
Ando, Y
Kawata, K
Park, O
Leung, PSC
Coppel, RL
Ansari, AA
Ridgway, WM
Gao, B
Lian, ZX
Flavell, R
He, XS
Gershwin, ME
AF Tsuda, Masanobu
Zhang, Weici
Yang, Guo-Xiang
Tsuneyama, Koichi
Ando, Yugo
Kawata, Kazuhito
Park, Ogyi
Leung, Patrick S. C.
Coppel, Ross L.
Ansari, Aftab A.
Ridgway, William M.
Gao, Bin
Lian, Zhe-Xiong
Flavell, Richard
He, Xiao-Song
Gershwin, M. Eric
TI Deletion of Interleukin (IL)-12p35 Induces Liver Fibrosis in
Dominant-Negative TGF beta Receptor Type II Mice
SO HEPATOLOGY
LA English
DT Article
ID PRIMARY BILIARY-CIRRHOSIS; T-CELLS; AUTOIMMUNE CHOLANGITIS; CYTOKINE
PROFILE; ANTIMITOCHONDRIAL AUTOANTIBODIES; MOUSE MODEL; TH17 CELLS;
INFLAMMATION; COLITIS; DISEASE
AB Mice with a dominant-negative transforming growth factor beta receptor restricted to T cells (dnTGF beta RII mice) develop an inflammatory biliary ductular disease that strongly resembles human primary biliary cirrhosis (PBC). Furthermore, deletion of the gene encoding interleukin (IL)-12p40 resulted in a strain (IL-12p40(-/-) dnTGF beta RII) with dramatically reduced autoimmune cholangitis. To further investigate the role of the IL-12 cytokine family in dnTGF beta RII autoimmune biliary disease, we deleted the gene encoding the IL-12p35 subunit from dnTGF beta RII mice, resulting in an IL-12p35(-/-) dnTGF beta RII strain which is deficient in two members of the IL-12 family, IL-12 and IL-35. In contrast to IL-12p40(-/-) mice, the IL-12p35 2/2 mice developed liver inflammation and bile duct damage with similar severity but delayed onset as the parental dnTGF beta RII mice. The p35(-/-) mice also demonstrated a distinct cytokine profile characterized by a shift from a T-helper 1 (Th1) to a Th17 response. Strikingly, liver fibrosis was frequently observed in IL-12p35(-/-) mice. In conclusion, IL-12p35(-/-) dnTGF beta RII mice, histologically and immunologically, reflect key features of PBC, providing a useful generic model to understand the immunopathology of human PBC. (HEPATOLOGY 2013;57:806-816)
C1 [Tsuda, Masanobu; Zhang, Weici; Yang, Guo-Xiang; Tsuneyama, Koichi; Ando, Yugo; Kawata, Kazuhito; Leung, Patrick S. C.; Lian, Zhe-Xiong; He, Xiao-Song; Gershwin, M. Eric] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA.
[Tsuda, Masanobu] Kansai Med Univ, Dept Emergency & Crit Care Med, Osaka, Japan.
[Tsuneyama, Koichi] Toyama Univ, Grad Sch Med & Pharmaceut Sci Res, Dept Diagnost Pathol, Toyama 930, Japan.
[Park, Ogyi; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
[Coppel, Ross L.] Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia.
[Ansari, Aftab A.] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA.
[Ridgway, William M.] Univ Cincinnati, Coll Med, Div Immunol Allergy & Rheumatol, Cincinnati, OH USA.
[Lian, Zhe-Xiong] Univ Sci & Technol China, Inst Immunol, Hefei 230026, Peoples R China.
[Lian, Zhe-Xiong] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Peoples R China.
[Flavell, Richard] Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA.
RP Gershwin, ME (reprint author), Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Sch Med, 451 Hlth Sci Dr,Ste 6510, Davis, CA 95616 USA.
EM zxlian1@ustc.edu.cn; megershwin@ucdavis.edu
RI Coppel, Ross/A-6626-2008
OI Coppel, Ross/0000-0002-4476-9124
FU National Institutes of Health [DK090019]
FX Financial support provided by National Institutes of Health grant
DK090019.
NR 53
TC 45
Z9 45
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD FEB
PY 2013
VL 57
IS 2
BP 806
EP 816
DI 10.1002/hep.25829
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 099TA
UT WOS:000315643400039
PM 22576253
ER
PT J
AU McGarrity, GJ
Hoyah, G
Winemiller, A
Andre, K
Stein, D
Blick, G
Greenberg, RN
Kinder, C
Zolopa, A
Binder-Scholl, G
Tebas, P
June, CH
Humeau, LM
Rebello, T
AF McGarrity, Gerard J.
Hoyah, Gloria
Winemiller, April
Andre, Kris
Stein, David
Blick, Gary
Greenberg, Richard N.
Kinder, Clifford
Zolopa, Andrew
Binder-Scholl, Gwen
Tebas, Pablo
June, Carl H.
Humeau, Laurent M.
Rebello, Tessio
TI Patient monitoring and follow-up in lentiviral clinical trials
SO JOURNAL OF GENE MEDICINE
LA English
DT Article
DE clinical trials; lentiviral vectors; safety monitoring
ID GENE-TRANSFER; VECTOR INTEGRATION; THERAPY; CELLS
AB Background Lentiviral vectors are being used with increasing frequency in human clinical trials. We were the first to use lentiviral vectors in clinical trials in 2003. Our lentiviral vector encoded a long RNA antisense sequence to the HIV-1 envelope and was used in an ex vivo autologous setting to provide viral load control in HIV-1 positive subjects failing anti-HIV therapy. A total of 65 subjects have been treated in Phase 1 and Phase 2 trials in six institutions. Methods Good manufacturing practices (GMP) lots of the lentiviral vector used in our clinical trials were assayed for the presence of replication competent lentivirus (RCL). RCL assays were conducted at two stages. The first testing was performed on samples collected immediately following bulk harvest of the GMP product lot and consisted of 1x108 cells used in production. RCL assays were also performed on aliquots of the final fill of the vector by the inoculation of at least 5% of the GMP final fill volume into C8166 cells, passaged for at least ten passages and tested for RCL by p24 enzyme-linked immunosorbent assay and vesicular stomatitis virus-G envelope DNA. Results Following 263 infusions of autologous, transduced cells, no adverse events have been detected in these subjects, with some followed for more than 8years following infusions. More than 4.3x1012 VRX496 proviral copies were administered to these 65 subjects. Conclusions Data from this small population suggest that there is no apparent risk for serious adverse events with the use of lentiviral vectors. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [McGarrity, Gerard J.; Hoyah, Gloria; Winemiller, April; Andre, Kris; Humeau, Laurent M.; Rebello, Tessio] VIRxSYS Corp, Gaithersburg, MD 20878 USA.
[Stein, David] Jacobi Med Ctr, Bronx, NY USA.
[Blick, Gary] Circle Med Ctr, Norwalk, CT USA.
[Greenberg, Richard N.] Univ Kentucky, Lexington, KY USA.
[Kinder, Clifford] Kinder Med Grp, Miami, FL USA.
[Zolopa, Andrew] Stanford Univ, Palo Alto, CA 94304 USA.
[Binder-Scholl, Gwen; Tebas, Pablo; June, Carl H.] Univ Penn, Abramson Family Canc Inst, Philadelphia, PA 19104 USA.
[Winemiller, April] NIH, Bethesda, MD 20892 USA.
[Binder-Scholl, Gwen] Adaptimmune LLC, Philadelphia, PA USA.
RP McGarrity, GJ (reprint author), VIRxSYS Corp, 105 Leekes Lot Way, Gaithersburg, MD 20878 USA.
EM bgmcgarr@aol.com
NR 17
TC 19
Z9 19
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1099-498X
J9 J GENE MED
JI J. Gene. Med.
PD FEB
PY 2013
VL 15
IS 2
BP 78
EP 82
DI 10.1002/jgm.2691
PG 5
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 097SS
UT WOS:000315494400003
PM 23322669
ER
PT J
AU Baker, DG
Woods, TA
Butchi, NB
Morgan, TM
Taylor, RT
Sunyakumthorn, P
Mukherjee, P
Lubick, KJ
Best, SM
Peterson, KE
AF Baker, David G.
Woods, Tyson A.
Butchi, Niranjan B.
Morgan, Timothy M.
Taylor, R. Travis
Sunyakumthorn, Piyanate
Mukherjee, Piyali
Lubick, Kirk J.
Best, Sonja M.
Peterson, Karin E.
TI Toll-like receptor 7 suppresses virus replication in neurons but does
not affect viral pathogenesis in a mouse model of Langat virus infection
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID WEST-NILE-VIRUS; TICK-BORNE ENCEPHALITIS; CD8(+) T-CELLS;
IMMUNE-RESPONSES; PROTECTIVE ROLE; MICROGLIA; BRAIN; NEUROPATHOGENESIS;
FLAVIVIRUS; PROTEIN
AB Toll-like receptor 7 (TLR7) recognizes guanidine-rich viral ssRNA and is an important mediator of peripheral immune responses to several ssRNA viruses. However, the role that TLR7 plays in regulating the innate immune response to ssRNA virus infections in specific organs such as the central nervous system (CNS) is not as clear. This study examined the influence of TLR7 on the neurovirulence of Langat virus (LGTV), a ssRNA tick-borne flavivirus. TLR7 deficiency did not substantially alter the onset or incidence of LGTV-induced clinical disease; however, it did significantly affect virus levels in the CNS with a log(10) increase in virus titres in brain tissue from TLR7-deficient mice. This difference in virus load was also observed following intracranial inoculation, indicating a direct effect of TLR7 deficiency on regulating virus replication in the brain. LGTV-induced type I interferon responses in the CNS were not dependent on TLR7, being higher in TLR7-deficient mice compared with wild-type controls. In contrast, induction of proinflammatory cytokines including tumour necrosis factor, CCL3, CCL4 and CXCL13 were dependent on TLR7. Thus, although TLR7 is not essential in controlling LGTV pathogenesis, it is important in controlling virus infection in neurons in the CNS, possibly by regulating neuroinflammatory responses.
C1 [Baker, David G.; Sunyakumthorn, Piyanate] Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA.
[Woods, Tyson A.; Butchi, Niranjan B.; Taylor, R. Travis; Mukherjee, Piyali; Lubick, Kirk J.; Best, Sonja M.; Peterson, Karin E.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Morgan, Timothy M.] Mississippi State Univ, Sch Vet Med, Dept Pathol, Mississippi State, MS 39762 USA.
RP Peterson, KE (reprint author), NIAID, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM petersonka@niaid.nih.gov
RI Peterson, Karin/D-1492-2016
OI Peterson, Karin/0000-0003-4177-7249
FU Louisiana State University School of Veterinary Medicine Competitive
Organized Research Program; Division of Intramural Research, National
Institutes of Health, National Institute of Allergy and Infectious
Diseases
FX The authors thank the Louisiana State University animal caretakers for
providing excellent animal care throughout these experiments. The
project was supported in part by Louisiana State University School of
Veterinary Medicine Competitive Organized Research Program and in part
by the Division of Intramural Research, National Institutes of Health,
National Institute of Allergy and Infectious Diseases.
NR 37
TC 9
Z9 9
U1 0
U2 8
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
J9 J GEN VIROL
JI J. Gen. Virol.
PD FEB
PY 2013
VL 94
BP 336
EP 347
DI 10.1099/vir.0.043984-0
PN 2
PG 12
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 098JR
UT WOS:000315546100012
PM 23136362
ER
PT J
AU Groninger, H
Burton, B
Hendricks, D
Sera, L
Sullivan, M
AF Groninger, Hunter
Burton, Brad
Hendricks, Danetta
Sera, Leah
Sullivan, Malgorzata
TI Our Double-Edged Sword: Interdisciplinary Approaches to Balancing
Symptom Control With Diversion and Safety Concerns in the Home Care
Setting
SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
LA English
DT Meeting Abstract
CT Annual Assembly of the
American-Academy-of-Hospice-and-Palliative-Medicine and the
Hospice-and-Palliative-Nurses-Association
CY MAR 13-16, 2013
CL New Orleans, LA
SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc
C1 [Groninger, Hunter] NIH, Bethesda, MD 20892 USA.
[Burton, Brad; Hendricks, Danetta; Sullivan, Malgorzata] Capital Caring, Washington, DC USA.
[Sera, Leah] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0885-3924
J9 J PAIN SYMPTOM MANAG
JI J. Pain Symptom Manage.
PD FEB
PY 2013
VL 45
IS 2
BP 332
EP 332
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal; Clinical
Neurology
SC Health Care Sciences & Services; General & Internal Medicine;
Neurosciences & Neurology
GA 100GE
UT WOS:000315684600042
ER
PT J
AU Groninger, H
Heintz, J
Murphy, B
AF Groninger, Hunter
Heintz, Jessica
Murphy, Brian
TI "Honor Thy Turf'': Advanced Consultant Etiquette Across Care Settings
SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
LA English
DT Meeting Abstract
CT Annual Assembly of the
American-Academy-of-Hospice-and-Palliative-Medicine and the
Hospice-and-Palliative-Nurses-Association
CY MAR 13-16, 2013
CL New Orleans, LA
SP Amer Acad Hosp and Palliat Med, Hosp and Palliat Nurses Assoc
C1 [Groninger, Hunter] NIH, Bethesda, MD 20892 USA.
[Heintz, Jessica] Capital Caring, Falls Church, VA USA.
[Murphy, Brian] Nathan Adelson Hosp, Las Vegas, NV USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0885-3924
J9 J PAIN SYMPTOM MANAG
JI J. Pain Symptom Manage.
PD FEB
PY 2013
VL 45
IS 2
BP 414
EP 415
PG 2
WC Health Care Sciences & Services; Medicine, General & Internal; Clinical
Neurology
SC Health Care Sciences & Services; General & Internal Medicine;
Neurosciences & Neurology
GA 100GE
UT WOS:000315684600169
ER
PT J
AU Managadze, D
Lobkovsky, AE
Wolf, YI
Shabalina, SA
Rogozin, IB
Koonin, EV
AF Managadze, David
Lobkovsky, Alexander E.
Wolf, Yuri I.
Shabalina, Svetlana A.
Rogozin, Igor B.
Koonin, Eugene V.
TI The Vast, Conserved Mammalian lincRNome
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID LONG NONCODING RNAS; OPEN READING FRAMES; HUMAN GENOME; TRANSCRIPTIONAL
ACTIVITY; NUCLEOTIDE RESOLUTION; GENE STRUCTURE; EXPRESSION; REVEALS;
IDENTIFICATION; EVOLUTION
AB We compare the sets of experimentally validated long intergenic non-coding (linc)RNAs from human and mouse and apply a maximum likelihood approach to estimate the total number of lincRNA genes as well as the size of the conserved part of the lincRNome. Under the assumption that the sets of experimentally validated lincRNAs are random samples of the lincRNomes of the corresponding species, we estimate the total lincRNome size at approximately 40,000 to 50,000 species, at least twice the number of protein-coding genes. We further estimate that the fraction of the human and mouse euchromatic genomes encoding lincRNAs is more than twofold greater than the fraction of protein-coding sequences. Although the sequences of most lincRNAs are much less strongly conserved than protein sequences, the extent of orthology between the lincRNomes is unexpectedly high, with 60 to 70% of the lincRNA genes shared between human and mouse. The orthologous mammalian lincRNAs can be predicted to perform equivalent functions; accordingly, it appears likely that thousands of evolutionarily conserved functional roles of lincRNAs remain to be characterized.
C1 [Managadze, David; Lobkovsky, Alexander E.; Wolf, Yuri I.; Shabalina, Svetlana A.; Rogozin, Igor B.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Managadze, D (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM koonin@ncbi.nlm.nih.gov
RI Shabalina, Svetlana/N-8939-2013
OI Shabalina, Svetlana/0000-0003-2272-7473
FU US Department of Health and Human Services (National Library of
Medicine)
FX This work was supported by intramural funds of the US Department of
Health and Human Services (National Library of Medicine). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 64
TC 20
Z9 21
U1 0
U2 16
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD FEB
PY 2013
VL 9
IS 2
AR e1002917
DI 10.1371/journal.pcbi.1002917
PG 9
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 100NT
UT WOS:000315708600025
PM 23468607
ER
PT J
AU Achyut, BR
Bader, DA
Robles, AI
Wangsa, D
Harris, CC
Ried, T
Yang, L
AF Achyut, B. R.
Bader, David A.
Robles, Ana I.
Wangsa, Darawalee
Harris, Curtis C.
Ried, Thomas
Yang, Li
TI Inflammation-Mediated Genetic and Epigenetic Alterations Drive Cancer
Development in the Neighboring Epithelium upon Stromal Abrogation of
TGF-beta Signaling
SO PLOS GENETICS
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR-BETA; TUMOR-SUPPRESSOR GENE;
DNA-DAMAGE RESPONSE; BREAST-CANCER; COLON-CANCER; MOUSE MODEL;
EXPRESSION; MICE; MICROENVIRONMENT
AB Deletion of tumor suppressor genes in stromal fibroblasts induces epithelial cancer development, suggesting an important role of stroma in epithelial homoeostasis. However, the underlying mechanisms remain to be elucidated. Here we report that deletion of the gene encoding TGF beta receptor 2 (Tgfbr2) in the stromal fibroblasts (Tgfbr2(fspKO)) induces inflammation and significant DNA damage in the neighboring epithelia of the forestomach. This results in loss or down-regulation of cyclin-dependent kinase inhibitors p15, p16, and p21, which contribute to the development of invasive squamous cell carcinoma (SCC). Anti-inflammation treatment restored p21 expression, delayed tumorigenesis, and increased survival of Tgfbr2(fspKO) mice. Our data demonstrate for the first time that inflammation is a critical player in the epigenetic silencing of p21 in tumor progression. Examination of human esophageal SCC showed a down-regulation of TGF beta receptor 2 (T beta RII) in the stromal fibroblasts, as well as increased inflammation, DNA damage, and loss or decreased p15/p16 expression. Our study suggests anti-inflammation may be a new therapeutic option in treating human SCCs with down-regulation of T beta RII in the stroma.
C1 [Achyut, B. R.; Yang, Li] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Bader, David A.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Robles, Ana I.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wangsa, Darawalee; Ried, Thomas] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Achyut, BR (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM yangl3@mail.nih.gov
FU NCI
FX This work was supported by NCI intramural funding to LY. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 57
TC 29
Z9 29
U1 0
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD FEB
PY 2013
VL 9
IS 2
AR e1003251
DI 10.1371/journal.pgen.1003251
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 099RG
UT WOS:000315638300015
PM 23408900
ER
PT J
AU Porcu, E
Medici, M
Pistis, G
Volpato, CB
Wilson, SG
Cappola, AR
Bos, SD
Deelen, J
den Heijer, M
Freathy, RM
Lahti, J
Liu, CY
Lopez, LM
Nolte, IM
O'Connell, JR
Tanaka, T
Trompet, S
Arnold, A
Bandinelli, S
Beekman, M
Bohringer, S
Brown, SJ
Buckley, BM
Camaschella, C
de Craen, AJM
Davies, G
de Visser, MCH
Ford, I
Forsen, T
Frayling, TM
Fugazzola, L
Gogele, M
Hattersley, AT
Hermus, AR
Hofman, A
Houwing-Duistermaat, JJ
Jensen, RA
Kajantie, E
Kloppenburg, M
Lim, EM
Masciullo, C
Mariotti, S
Minelli, C
Mitchell, BD
Nagaraja, R
Netea-Maier, RT
Palotie, A
Persani, L
Piras, MG
Psaty, BM
Raikkonen, K
Richards, JB
Rivadeneira, F
Sala, C
Sabra, MM
Sattar, N
Shields, BM
Soranzo, N
Starr, JM
Stott, DJ
Sweep, FCGJ
Usala, G
van der Klauw, MM
van Heemst, D
van Mullem, A
Vermeulen, SH
Visser, WE
Walsh, JP
Westendorp, RGJ
Widen, E
Zhai, GJ
Cucca, F
Deary, IJ
Eriksson, JG
Ferrucci, L
Fox, CS
Jukema, JW
Kiemeney, LA
Pramstaller, PP
Schlessinger, D
Shuldiner, AR
Slagboom, EP
Uitterlinden, AG
Vaidya, B
Visser, TJ
Wolffenbuttel, BHR
Meulenbelt, I
Rotter, JI
Spector, TD
Hicks, AA
Toniolo, D
Sanna, S
Peeters, RP
Naitza, S
AF Porcu, Eleonora
Medici, Marco
Pistis, Giorgio
Volpato, Claudia B.
Wilson, Scott G.
Cappola, Anne R.
Bos, Steffan D.
Deelen, Joris
den Heijer, Martin
Freathy, Rachel M.
Lahti, Jari
Liu, Chunyu
Lopez, Lorna M.
Nolte, Ilja M.
O'Connell, Jeffrey R.
Tanaka, Toshiko
Trompet, Stella
Arnold, Alice
Bandinelli, Stefania
Beekman, Marian
Bohringer, Stefan
Brown, Suzanne J.
Buckley, Brendan M.
Camaschella, Clara
de Craen, Anton J. M.
Davies, Gail
de Visser, Marieke C. H.
Ford, Ian
Forsen, Tom
Frayling, Timothy M.
Fugazzola, Laura
Goegele, Martin
Hattersley, Andrew T.
Hermus, Ad R.
Hofman, Albert
Houwing-Duistermaat, Jeanine J.
Jensen, Richard A.
Kajantie, Eero
Kloppenburg, Margreet
Lim, Ee M.
Masciullo, Corrado
Mariotti, Stefano
Minelli, Cosetta
Mitchell, Braxton D.
Nagaraja, Ramaiah
Netea-Maier, Romana T.
Palotie, Aarno
Persani, Luca
Piras, Maria G.
Psaty, Bruce M.
Raikkonen, Katri
Richards, J. Brent
Rivadeneira, Fernando
Sala, Cinzia
Sabra, Mona M.
Sattar, Naveed
Shields, Beverley M.
Soranzo, Nicole
Starr, John M.
Stott, David J.
Sweep, Fred C. G. J.
Usala, Gianluca
van der Klauw, Melanie M.
van Heemst, Diana
van Mullem, Alies
Vermeulen, Sita H.
Visser, W. Edward
Walsh, John P.
Westendorp, Rudi G. J.
Widen, Elisabeth
Zhai, Guangju
Cucca, Francesco
Deary, Ian J.
Eriksson, Johan G.
Ferrucci, Luigi
Fox, Caroline S.
Jukema, J. Wouter
Kiemeney, Lambertus A.
Pramstaller, Peter P.
Schlessinger, David
Shuldiner, Alan R.
Slagboom, Eline P.
Uitterlinden, Andre G.
Vaidya, Bijay
Visser, Theo J.
Wolffenbuttel, Bruce H. R.
Meulenbelt, Ingrid
Rotter, Jerome I.
Spector, Tim D.
Hicks, Andrew A.
Toniolo, Daniela
Sanna, Serena
Peeters, Robin P.
Naitza, Silvia
TI A Meta-Analysis of Thyroid-Related Traits Reveals Novel Loci and
Gender-Specific Differences in the Regulation of Thyroid Function
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; FACTOR BINDING PROTEIN-5; HORMONE PATHWAY
GENES; SERUM TSH; COMMON VARIATION; CLEFT-PALATE; EXPRESSION; GROWTH;
HYPOTHYROIDISM; THYROTROPIN
AB Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.
C1 [Porcu, Eleonora; Piras, Maria G.; Usala, Gianluca; Cucca, Francesco; Sanna, Serena; Naitza, Silvia] CNR, IRGB, Cagliari, Italy.
[Porcu, Eleonora; Cucca, Francesco] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy.
[Medici, Marco; Rivadeneira, Fernando; van Mullem, Alies; Visser, W. Edward; Uitterlinden, Andre G.; Visser, Theo J.; Peeters, Robin P.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Pistis, Giorgio; Camaschella, Clara; Masciullo, Corrado; Sala, Cinzia; Toniolo, Daniela] San Raffaele Res Inst, Div Genet & Cell Biol, Milan, Italy.
[Pistis, Giorgio] Univ Trieste, Trieste, Italy.
[Volpato, Claudia B.; Goegele, Martin; Minelli, Cosetta; Pramstaller, Peter P.; Hicks, Andrew A.] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy.
[Volpato, Claudia B.; Goegele, Martin; Minelli, Cosetta; Pramstaller, Peter P.; Hicks, Andrew A.] Med Univ Lubeck, D-23538 Lubeck, Germany.
[Wilson, Scott G.; Brown, Suzanne J.; Lim, Ee M.; Walsh, John P.] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia.
[Wilson, Scott G.; Richards, J. Brent; Zhai, Guangju; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Wilson, Scott G.; Walsh, John P.] Univ Western Australia, Sch Med & Pharmacol, Crawley, WA, Australia.
[Cappola, Anne R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Bos, Steffan D.; Deelen, Joris; Beekman, Marian; Slagboom, Eline P.; Meulenbelt, Ingrid] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Bos, Steffan D.; Deelen, Joris; Beekman, Marian; Slagboom, Eline P.; Meulenbelt, Ingrid] Netherlands Consortium Hlth Ageing, Leiden, Netherlands.
[den Heijer, Martin; Hermus, Ad R.; Netea-Maier, Romana T.] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands.
[den Heijer, Martin] Free Univ Amsterdam, Dept Internal Med, Med Ctr, Amsterdam, Netherlands.
[Freathy, Rachel M.; Frayling, Timothy M.] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England.
[Lahti, Jari; Raikkonen, Katri] Univ Helsinki, Inst Behav Sci, Helsinki, Finland.
[Liu, Chunyu] NHLBI, Ctr Populat Studies, Framingham, MA USA.
[Lopez, Lorna M.; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
[Lopez, Lorna M.; Davies, Gail; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland.
[Nolte, Ilja M.] Univ Groningen, Univ Med Ctr Groningen, Unit Genet Epidemiol & Bioinformat, Dept Epidemiol, Groningen, Netherlands.
[O'Connell, Jeffrey R.; Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
[Trompet, Stella; de Craen, Anton J. M.] Leiden Univ, Dept Gerontol & Geriatr, Med Ctr, Leiden, Netherlands.
[Arnold, Alice; Jensen, Richard A.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Arnold, Alice; Jensen, Richard A.] Univ Washington, Dept Med, Seattle, WA USA.
[Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy.
[Bohringer, Stefan; Houwing-Duistermaat, Jeanine J.; van Heemst, Diana; Westendorp, Rudi G. J.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Buckley, Brendan M.] Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland.
[Camaschella, Clara] Vita & Salute Univ, San Raffaele Sci Inst, Milan, Italy.
[de Visser, Marieke C. H.; Vermeulen, Sita H.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6525 ED Nijmegen, Netherlands.
[Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
[Forsen, Tom; Kajantie, Eero; Eriksson, Johan G.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Forsen, Tom; Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Forsen, Tom; Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland.
[Forsen, Tom] Vaasa Hlth Care Ctr, Diabet Unit, Vaasa, Finland.
[Fugazzola, Laura] Univ Milan, Fdn Ca Granda Policlin, Endocrine Unit, Milan, Italy.
[Fugazzola, Laura] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
[Hattersley, Andrew T.; Shields, Beverley M.] Univ Exeter, Peninsula NIHR Clin Res Facil, Peninsula Coll Med & Dent, Exeter, Devon, England.
[Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] NCHA, Rotterdam, Netherlands.
[Kajantie, Eero] Univ Helsinki, Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland.
[Kajantie, Eero] Univ Helsinki, Helsinki, Finland.
[Kloppenburg, Margreet] Leiden Univ, Dept Clin Epidemiol & Rheumatol, Med Ctr, Leiden, Netherlands.
[Lim, Ee M.] Pathwest Lab Med WA, Nedlands, WA, Australia.
[Mariotti, Stefano] Univ Cagliari, Dipartimento Scienze Med, Cagliari, Italy.
[Nagaraja, Ramaiah; Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA.
[Palotie, Aarno; Soranzo, Nicole] Wellcome Trust Sanger Inst, Cambridge, England.
[Palotie, Aarno; Widen, Elisabeth] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Palotie, Aarno] Univ Helsinki, Dept Med Genet, Helsinki, Finland.
[Palotie, Aarno] Univ Cent Hosp, Helsinki, Finland.
[Persani, Luca] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
[Persani, Luca] IRCCS Osped San Luca, Div Endocrinol & Metab Dis, Milan, Italy.
[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.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA.
[Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Dept Med, Montreal, PQ H3T 1E2, Canada.
[Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Dept Human Genet, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada.
[Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Dept Epidemiol, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada.
[Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Dept Biostat, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada.
[Sabra, Mona M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Sattar, Naveed] Fac Med, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland.
[Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland.
[Stott, David J.] Univ Glasgow, Acad Sect Geriatr Med, Fac Med, Glasgow, Lanark, Scotland.
[Sweep, Fred C. G. J.] Radboud Univ Nijmegen, Dept Lab Med, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[van der Klauw, Melanie M.; Wolffenbuttel, Bruce H. R.] Univ Groningen, Univ Med Ctr Groningen, LifeLines Cohort Study, Groningen, Netherlands.
[van der Klauw, Melanie M.; Wolffenbuttel, Bruce H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands.
[Zhai, Guangju] Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF, Canada.
[Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland.
[Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland.
[Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.
[Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands.
[Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Dept Urol, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy.
[Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany.
[Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
[Vaidya, Bijay] Royal Devon & Exeter NHS Fdn Trust, Diabet Endocrinol & Vasc Hlth Ctr, Exeter, Devon, England.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Toniolo, Daniela] CNR, Inst Mol Genet, I-27100 Pavia, Italy.
RP Porcu, E (reprint author), CNR, IRGB, Cittadella Univ Monserrato, Cagliari, Italy.
EM serena.sanna@irgb.cnr.it; r.peeters@erasmusmc.nl;
silvia.naitza@irgb.cnr.it
RI Netea-Maier, R.T./L-4543-2015; Deary, Ian/C-6297-2009; Rivadeneira,
Fernando/O-5385-2015; Vermeulen, H.H.M./L-4716-2015; van der Klauw,
Melanie/A-2138-2014; Kiemeney, Lambertus/D-3357-2009; Pramstaller,
Peter/C-2357-2008; Sweep, C.G.J./H-8096-2014; Camaschella,
Clara/A-3289-2015; Peeters, Robin/P-3603-2014; Visser, W.
Edward/C-4062-2015; Hermus, A.R.M.M./H-8043-2014; Netea,
Mihai/N-5155-2014; Slagboom, P. Eline/R-4790-2016; Naitza,
Silvia/D-5620-2017; Hicks, Andrew/E-9518-2017;
OI Vaidya, Bijay/0000-0002-2223-0494; Wolffenbuttel, Bruce
H.R./0000-0001-9262-6921; Eriksson, Johan/0000-0002-2516-2060; Mitchell,
Braxton/0000-0003-4920-4744; Hattersley, Andrew/0000-0001-5620-473X;
Lahti, Jari/0000-0002-4310-5297; Raikkonen, Katri/0000-0003-3124-3470;
Persani, Luca/0000-0003-2068-9581; Rivadeneira,
Fernando/0000-0001-9435-9441; van der Klauw,
Melanie/0000-0001-7178-009X; Kiemeney, Lambertus/0000-0002-2368-1326;
Visser, W. Edward/0000-0002-5248-863X; Slagboom, P.
Eline/0000-0002-2875-4723; Hicks, Andrew/0000-0001-6320-0411; Freathy,
Rachel/0000-0003-4152-2238; Walsh, John/0000-0002-1766-2612; piras,
maria grazia/0000-0001-9004-0900; sanna, serena/0000-0002-3768-1749;
Beekman, Marian/0000-0003-0585-6206; Deelen, Joris/0000-0003-4483-3701;
Soranzo, Nicole/0000-0003-1095-3852
FU NIH [AG-023629, AG-15928, AG-20098, AG-027058, 263 MD 9164, 263 MD
821336,, _NO1-AG-1-2109, U01 HL72515, R01 AG18728]; NIH General Clinical
Research Centers Program, National Center for Research Resources (NCRR);
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, HHSN268201200036C,
HL080295, HL087652, HL105756, N01-HC-25195, N02-HL-6-4278]; MedStar
Research Institute; NINDS; National Center of Advancing Translational
Technologies CTSI [UL1TR000124]; National Institute of Diabetes and
Digestive and Kidney Diseases [DK063491]; Robert Dawson Evans Endowment;
Italian Ministry of Health [ICS110.1/RF97.71]; Ricerca Finalizzata;
Ministry of Health and Department of Educational Assistance, University
and Research of the Autonomous Province of Bolzano; European Union
[259679, 223004, HEALTH-F4-2007-201413, 257082, HEALTH-F5-2011-282510];
Dutch Innovation-Oriented Research Program on Genomics [SenterNovem
IGE05007]; Netherlands Organization for Scientific Research (NWO)
[050-060-810, 75.010.2005.011, 911-03-012, MW 904-61-095, 911-03-016,
917 66344, 175.010.2007.006]; South Tyrolean Sparkasse Foundation;
Radboud University Nijmegen Medical Centre; University of Maryland
General Clinical Research Center [M01 RR 16500]; Johns Hopkins
University General Clinical Research Center [M01 RR 000052]; Baltimore
Veterans Administration Geriatric Research and Education Clinical Center
(GRECC); Netherlands Research Institute for Diseases in the Elderly
[014-93-015, RIDE2]; Erasmus Medical Center and Erasmus University,
Rotterdam; Netherlands Organization for the Health Research and
Development (ZonMw); Dutch Ministry for Health, Welfare and Sports;
European Commission (DG XII); Municipality of Rotterdam; German
Bundesministerium fuer Forschung und Technology [01 AK 803 A-H, 01 IG
07015 G]; Wellcome Trust [WT089062, WT091310, 085541/Z/08/Z]; English
Department of Health, National Institute for Health Research (NIHR)
Comprehensive Biomedical Research Centre; Canadian Institutes of Health
Research; Canadian Foundation for Innovation; Fonds de la Recherche en
Sante Quebec; Ministere du Developpement Economique, de l'Innovation et
de l'Exportation;; Lady Davis Institute of the Jewish General Hospital
(JBR); Australian National Health and Medical Research Council [1010494,
1031422]; Sir Charles Gairdner Hospital Research Fund; Italian
"Compagnia di San Paolo''; Italian "Fondazione Cariplo''; Leiden
University Medical Centre; Dutch Arthritis Association; Pfizer, Groton,
CT, USA; Dutch Centre of Medical System Biology; Netherlands Genomics
Initiative (NGI); Netherlands Consortium of Healthy Aging [050-060-810];
Academy of Finland; Finnish Diabetes Research Society; Folkhalsan
Research Foundation; Novo Nordisk Foundation; Finska Lakaresallskapet;
Signe and Ane Gyllenberg Foundation; University of Helsinki; European
Science Foundation (EUROSTRESS); Finnish Ministry of Education; Ahokas
Foundation; Emil Aaltonen Foundation; Juho Vainio Foundation;
Biotechnology and Biological Sciences Research Council (BBSRC);
Engineering and Physical Sciences Research Council (EPSRC); Economic and
Social Research Council (ESRC); Medical Research Council (MRC), as part
of the cross-council Lifelong Health and Wellbeing Initiative; AXA
Research Fund; Research Into Ageing; Help the Aged/Research Into Ageing
(Disconnected Mind); Economic Structure Enhancing Fund (FES) of the
Dutch government; Dutch Ministry of Economic Affairs; Dutch Ministry of
Education, Culture and Science; Northern Netherlands Collaboration of
Provinces (SNN); Province of Groningen; University of Groningen; Dutch
Kidney Foundation and Dutch Diabetes Research Foundation; Bristol-Myers
Squibb; Netherlands Heart Foundation [2001 D 032]; National Computing
Facilities Foundation (NCF), Netherlands; Endocrine Research Fund
FX This work was supported by Intramural Research Program of the NIH
(grants AG-023629, AG-15928, AG-20098, AG-027058, 263 MD 9164, 263 MD
821336,_NO1-AG-1-2109, U01 HL72515, R01 AG18728) and NIH General
Clinical Research Centers Program, National Center for Research
Resources (NCRR); 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, HHSN268201200036C, and NHLBI grants HL080295, HL087652,
HL105756, contracts N01-HC-25195 and N02-HL-6-4278); R&D contract with
MedStar Research Institute; NINDS contract; National Center of Advancing
Translational Technologies CTSI grant UL1TR000124; National Institute of
Diabetes and Digestive and Kidney Diseases grant DK063491; Robert Dawson
Evans Endowment; Italian Ministry of Health grants ICS110.1/RF97.71 and
Ricerca Finalizzata 2008; Ministry of Health and Department of
Educational Assistance, University and Research of the Autonomous
Province of Bolzano; European Union's Seventh Framework Programme (grant
agreements FP7/2007-2011 and FP7/2007-2013, 259679, 223004 and ENGAGE
project grant agreement HEALTH-F4-2007-201413, EPIGENESYS grant
agreement 257082, BLUEPRINT grant agreement HEALTH-F5-2011-282510);
Dutch Innovation-Oriented Research Program on Genomics (SenterNovem
IGE05007); Netherlands Organization for Scientific Research (NWO)
(grants 050-060-810, 175.010.2005.011, 911-03-012, 050-060-810, MW
904-61-095, 911-03-016, 917 66344, 911-03-012, 175.010.2007.; 006);
South Tyrolean Sparkasse Foundation; Radboud University Nijmegen Medical
Centre; University of Maryland General Clinical Research Center grant
M01 RR 16500; Johns Hopkins University General Clinical Research Center,
grant M01 RR 000052; Baltimore Veterans Administration Geriatric
Research and Education Clinical Center (GRECC); Netherlands Research
Institute for Diseases in the Elderly (grant 014-93-015; RIDE2); Erasmus
Medical Center and Erasmus University, Rotterdam; Netherlands
Organization for the Health Research and Development (ZonMw); Dutch
Ministry for Health, Welfare and Sports; European Commission (DG XII);
Municipality of Rotterdam; German Bundesministerium fuer Forschung und
Technology grants 01 AK 803 A-H, 01 IG 07015 G; Wellcome Trust (grants
WT089062, WT098051, WT091310,085541/Z/08/Z); English Department of
Health, National Institute for Health Research (NIHR) Comprehensive
Biomedical Research Centre; Canadian Institutes of Health Research,
Canadian Foundation for Innovation; Fonds de la Recherche en Sante
Quebec, Ministere du Developpement Economique, de l'Innovation et de
l'Exportation; Lady Davis Institute of the Jewish General Hospital
(JBR); Australian National Health and Medical Research Council (grants
1010494, 1031422); Sir Charles Gairdner Hospital Research Fund; Italian
"Compagnia di San Paolo''; Italian "Fondazione Cariplo''; Leiden
University Medical Centre; Dutch Arthritis Association; Pfizer, Groton,
CT, USA; Dutch Centre of Medical System Biology; Netherlands Genomics
Initiative (NGI), Netherlands Consortium of Healthy Aging'' (grant
050-060-810); Academy of Finland; Finnish Diabetes Research Society;
Folkhalsan Research Foundation; Novo Nordisk Foundation; Finska
Lakaresallskapet, Signe and Ane Gyllenberg Foundation; University of
Helsinki; European Science Foundation (EUROSTRESS); Finnish Ministry of
Education; Ahokas Foundation; Emil Aaltonen Foundation; Juho Vainio
Foundation; Biotechnology and Biological Sciences Research Council
(BBSRC); Engineering and Physical Sciences Research Council (EPSRC);
Economic and Social Research Council (ESRC); Medical Research Council
(MRC), as part of the cross-council Lifelong Health and Wellbeing
Initiative; AXA Research Fund; Research Into Ageing and programme grants
from Help the Aged/Research Into Ageing (Disconnected Mind); Economic
Structure Enhancing Fund (FES) of the Dutch government; Dutch Ministry
of Economic Affairs; Dutch Ministry of Education, Culture and Science;
Northern Netherlands Collaboration of Provinces (SNN); Province of
Groningen; University of Groningen; Dutch Kidney Foundation and Dutch
Diabetes Research Foundation; Bristol-Myers Squibb; Netherlands Heart
Foundation grant 2001 D 032; National Computing Facilities Foundation
(NCF), Netherlands, for the use of supercomputer facilities; Endocrine
Research Fund; http://www.chs-nhlbi.org/pi.htm. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 85
TC 44
Z9 45
U1 0
U2 30
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD FEB
PY 2013
VL 9
IS 2
AR e1003266
DI 10.1371/journal.pgen.1003266
PG 20
WC Genetics & Heredity
SC Genetics & Heredity
GA 099RG
UT WOS:000315638300025
PM 23408906
ER
PT J
AU Uthman, S
Bar, C
Scheidt, V
Liu, SH
ten Have, S
Giorgini, F
Stark, MJR
Schaffrath, R
AF Uthman, Shanow
Baer, Christian
Scheidt, Viktor
Liu, Shihui
ten Have, Sara
Giorgini, Flaviano
Stark, Michael J. R.
Schaffrath, Raffael
TI The Amidation Step of Diphthamide Biosynthesis in Yeast Requires DPH6, a
Gene Identified through Mining the DPH1-DPH5 Interaction Network
SO PLOS GENETICS
LA English
DT Article
ID KLUYVEROMYCES-LACTIS ZYMOCIN; FUNGAL PROTEIN-SYNTHESIS; ADP-RIBOSYLATING
TOXINS; ELONGATION-FACTOR EEF2; SACCHAROMYCES-CEREVISIAE;
DIPHTHERIA-TOXIN; TRANSLATION ELONGATION-FACTOR-2; S-ADENOSYLMETHIONINE;
CRYSTAL-STRUCTURE; ESCHERICHIA-COLI
AB Diphthamide is a highly modified histidine residue in eukaryal translation elongation factor 2 (eEF2) that is the target for irreversible ADP ribosylation by diphtheria toxin (DT). In Saccharomyces cerevisiae, the initial steps of diphthamide biosynthesis are well characterized and require the DPH1-DPH5 genes. However, the last pathway step-amidation of the intermediate diphthine to diphthamide-is ill-defined. Here we mine the genetic interaction landscapes of DPH1-DPH5 to identify a candidate gene for the elusive amidase (YLR143w/DPH6) and confirm involvement of a second gene (YBR246w/DPH7) in the amidation step. Like dph1-dph5, dph6 and dph7 mutants maintain eEF2 forms that evade inhibition by DT and sordarin, a diphthamide-dependent antifungal. Moreover, mass spectrometry shows that dph6 and dph7 mutants specifically accumulate diphthine-modified eEF2, demonstrating failure to complete the final amidation step. Consistent with an expected requirement for ATP in diphthine amidation, Dph6 contains an essential adenine nucleotide hydrolase domain and binds to eEF2. Dph6 is therefore a candidate for the elusive amidase, while Dph7 apparently couples diphthine synthase (Dph5) to diphthine amidation. The latter conclusion is based on our observation that dph7 mutants show drastically upregulated interaction between Dph5 and eEF2, indicating that their association is kept in check by Dph7. Physiologically, completion of diphthamide synthesis is required for optimal translational accuracy and cell growth, as indicated by shared traits among the dph mutants including increased ribosomal -1 frameshifting and altered responses to translation inhibitors. Through identification of Dph6 and Dph7 as components required for the amidation step of the diphthamide pathway, our work paves the way for a detailed mechanistic understanding of diphthamide formation.
C1 [Uthman, Shanow; Baer, Christian; Giorgini, Flaviano; Schaffrath, Raffael] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England.
[Baer, Christian; Scheidt, Viktor; Schaffrath, Raffael] Univ Kassel, Inst Biol, FG Mikrobiol, D-34125 Kassel, Germany.
[Liu, Shihui] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[ten Have, Sara; Stark, Michael J. R.] Univ Dundee, Ctr Gene Regulat & Express, Coll Life Sci, Dundee, Scotland.
RP Uthman, S (reprint author), Univ Leicester, Dept Genet, Univ Rd, Leicester LE1 7RH, Leics, England.
EM m.j.r.stark@dundee.ac.uk; schaffrath@uni-kassel.de
RI Stark, Michael/B-2815-2014
OI Stark, Michael/0000-0001-9086-191X
FU Wellcome Trust [083524/Z/07/Z]; U.S. National Institute of Allergy and
Infectious Diseases [1ZIAAI000929-09]; Biotechnology and Biological
Sciences Research Council (BBSRC) [BB/F0191629/1, BB/F019106/1]; HOPE
Against Cancer Foundation for Leicestershire and Rutland [RM33G0118];
Department of Genetics, University of Leicester; Institute of Biology,
Division of Microbiology, University of Kassel, Germany; Alexander von
Humboldt Foundation [3.1-3 FLFDEU-1037031]; Bonn Bad Godesberg, Germany;
Royal Society, UK [2008/R2]
FX We gratefully acknowledge support for this work from the Wellcome Trust
(083524/Z/07/Z), by a grant from the U.S. National Institute of Allergy
and Infectious Diseases Intramural Programme to SL (1ZIAAI000929-09), by
joint research grants from the Biotechnology and Biological Sciences
Research Council (BBSRC) to MJRS (BB/F0191629/1) as well as RS
(BB/F019106/1), and by the HOPE Against Cancer Foundation for
Leicestershire and Rutland through a OVCA1/DPH1 related PhD studentship
(RM33G0118) awarded to SU. CB received support from the Department of
Genetics, University of Leicester, and the Institute of Biology,
Division of Microbiology, University of Kassel, Germany. RS gratefully
acknowledges support from the Feodor Lynen Fellowship Alumnus Programme
of the Alexander von Humboldt Foundation (3.1-3 FLFDEU-1037031), Bonn
Bad Godesberg, Germany, and from the Royal Society (2008/R2 grant), UK.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 83
TC 11
Z9 13
U1 1
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD FEB
PY 2013
VL 9
IS 2
AR e1003334
DI 10.1371/journal.pgen.1003334
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 099RG
UT WOS:000315638300073
PM 23468660
ER
PT J
AU Vimaleswaran, KS
Berry, DJ
Lu, C
Tikkanen, E
Pilz, S
Hiraki, LT
Cooper, JD
Dastani, Z
Li, R
Houston, DK
Wood, AR
Michaelsson, K
Vandenput, L
Zgaga, L
Yerges-Armstrong, LM
McCarthy, MI
Dupuis, J
Kaakinen, M
Kleber, ME
Jameson, K
Arden, N
Raitakari, O
Viikari, J
Lohman, KK
Ferrucci, L
Melhus, H
Ingelsson, E
Byberg, L
Lind, L
Lorentzon, M
Salomaa, V
Campbell, H
Dunlop, M
Mitchell, BD
Herzig, KH
Pouta, A
Hartikainen, AL
Streeten, EA
Theodoratou, E
Jula, A
Wareham, NJ
Ohlsson, C
Frayling, TM
Kritchevsky, SB
Spector, TD
Richards, JB
Lehtimaki, T
Ouwehand, WH
Kraft, P
Cooper, C
Marz, W
Power, C
Loos, RJF
Wang, TJ
Jarvelin, MR
Whittaker, JC
Hingorani, AD
Hypponen, E
AF Vimaleswaran, Karani S.
Berry, Diane J.
Lu, Chen
Tikkanen, Emmi
Pilz, Stefan
Hiraki, Linda T.
Cooper, Jason D.
Dastani, Zari
Li, Rui
Houston, Denise K.
Wood, Andrew R.
Michaelsson, Karl
Vandenput, Liesbeth
Zgaga, Lina
Yerges-Armstrong, Laura M.
McCarthy, Mark I.
Dupuis, Josee
Kaakinen, Marika
Kleber, Marcus E.
Jameson, Karen
Arden, Nigel
Raitakari, Olli
Viikari, Jorma
Lohman, Kurt K.
Ferrucci, Luigi
Melhus, Hakan
Ingelsson, Erik
Byberg, Liisa
Lind, Lars
Lorentzon, Mattias
Salomaa, Veikko
Campbell, Harry
Dunlop, Malcolm
Mitchell, Braxton D.
Herzig, Karl-Heinz
Pouta, Anneli
Hartikainen, Anna-Liisa
Streeten, Elizabeth A.
Theodoratou, Evropi
Jula, Antti
Wareham, Nicholas J.
Ohlsson, Claes
Frayling, Timothy M.
Kritchevsky, Stephen B.
Spector, Timothy D.
Richards, J. Brent
Lehtimaki, Terho
Ouwehand, Willem H.
Kraft, Peter
Cooper, Cyrus
Maerz, Winfried
Power, Chris
Loos, Ruth J. F.
Wang, Thomas J.
Jaervelin, Marjo-Riitta
Whittaker, John C.
Hingorani, Aroon D.
Hyppoenen, Elina
CA Genetic Invest Anthropometric Trai
TI Causal Relationship between Obesity and Vitamin D Status: Bi-Directional
Mendelian Randomization Analysis of Multiple Cohorts
SO PLOS MEDICINE
LA English
DT Article
ID BODY-MASS INDEX; CARDIOVASCULAR-DISEASE RISK; GENOME-WIDE ASSOCIATION;
GENETIC-VARIANTS; INSTRUMENTAL VARIABLES; D DEFICIENCY;
25-HYDROXYVITAMIN D; D INSUFFICIENCY; COMMON OBESITY; PREVALENCE
AB Background: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH) D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis.
Methods and Findings: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH) D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH) D (p = 6.52x10(-27)). The BMI allele score was associated both with BMI (p = 6.30x10(-62)) and 25(OH) D (20.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH) D (p <= 8.07x10(-57) for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH) D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH) D with BMI, a finding that was confirmed using data from the GIANT consortium (p >= 0.57 for both vitamin D scores).
Conclusions: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH) D, while any effects of lower 25(OH) D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.
C1 [Vimaleswaran, Karani S.; Berry, Diane J.; Power, Chris; Hyppoenen, Elina] UCL Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England.
[Vimaleswaran, Karani S.; Berry, Diane J.; Power, Chris; Hyppoenen, Elina] UCL Inst Child Hlth, MRC Ctr Epidemiol Child Hlth, London, England.
[Lu, Chen; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Tikkanen, Emmi] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Tikkanen, Emmi; Salomaa, Veikko; Jula, Antti] Natl Inst Hlth & Welf, Helsinki, Finland.
[Pilz, Stefan] Med Univ Graz, Div Endocrinol & Metab, Dept Internal Med, Graz, Austria.
[Pilz, Stefan] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Dept Epidemiol & Biostat, Amsterdam, Netherlands.
[Hiraki, Linda T.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Cooper, Jason D.] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Juvenile Diabet Res Fdn Wellcome Trust Diabet & I, Cambridge, England.
[Dastani, Zari] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3T 1E2, Canada.
[Li, Rui; Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Med, Montreal, PQ H3T 1E2, Canada.
[Li, Rui; Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Human Genet, Montreal, PQ H3T 1E2, Canada.
[Li, Rui; Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Epidemiol & Biostat, Montreal, PQ H3T 1E2, Canada.
[Houston, Denise K.; Kritchevsky, Stephen B.] Wake Forest Sch Med, Sect Gerontol & Geriatr Med, Dept Internal Med, Winston Salem, NC USA.
[Wood, Andrew R.; Frayling, Timothy M.] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England.
[Michaelsson, Karl; Byberg, Liisa] Uppsala Univ, Dept Surg Sci, Uppsala, Sweden.
[Vandenput, Liesbeth; Lorentzon, Mattias; Ohlsson, Claes] Univ Gothenburg, Inst Med, Dept Internal Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden.
[Zgaga, Lina; Campbell, Harry; Theodoratou, Evropi] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Zgaga, Lina] Univ Zagreb, Sch Med, Andrija Stampar Sch Publ Hlth, Zagreb 41001, Croatia.
[Yerges-Armstrong, Laura M.; Mitchell, Braxton D.; Streeten, Elizabeth A.] Univ Maryland, Sch Med, Div Endocrinol, Baltimore, MD 21201 USA.
[McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England.
[Dupuis, Josee] NHLBI, Framingham, MA USA.
[Kaakinen, Marika; Herzig, Karl-Heinz; Jaervelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Kaakinen, Marika; Herzig, Karl-Heinz; Jaervelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Kleber, Marcus E.] LURIC Study Non Profit LLC, Freiburg, Germany.
[Kleber, Marcus E.] Heidelberg Univ, Mannheim Inst Publ Hlth, Mannheim Med Fac, Social & Prevent Med, Mannheim, Germany.
[Jameson, Karen; Cooper, Cyrus] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England.
[Arden, Nigel] Botnar Res Ctr, NIHR Musculoskeletal BRU, Oxford, England.
[Arden, Nigel] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England.
[Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Raitakari, Olli] Univ Turku, Dept Clin Physiol & Nucl Med, Turku, Finland.
[Raitakari, Olli; Viikari, Jorma] Turku Univ Hosp, FIN-20520 Turku, Finland.
[Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland.
[Lohman, Kurt K.] Wake Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA.
[Ferrucci, Luigi] Harbor Hosp, Clin Res Branch, Baltimore, MD USA.
[Melhus, Hakan; Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Dunlop, Malcolm] Univ Edinburgh, Inst Genet & Mol Med, Colon Canc Genet Grp & Acad Coloproctol, Edinburgh EH8 9YL, Midlothian, Scotland.
[Dunlop, Malcolm] Western Gen Hosp Edinburgh, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
[Herzig, Karl-Heinz] Univ Oulu, Inst Biomed, Oulu, Finland.
[Herzig, Karl-Heinz] Kuopio Univ Hosp, Dept Psychiat, SF-70210 Kuopio, Finland.
[Pouta, Anneli] Univ Oulu, Dept Publ Hlth Sci & Gen Practice, Oulu, Finland.
[Hartikainen, Anna-Liisa] Univ Oulu, Dept Obstet & Gynaecol & Publ Hlth & Gen Practice, Oulu, Finland.
[Wareham, Nicholas J.; Loos, Ruth J. F.] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
[Spector, Timothy D.; Richards, J. Brent] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Lehtimaki, Terho] Tampere Univ Hosp, Dept Clin Chem, Fimlab Labs, FIN-33521 Tampere, Finland.
[Lehtimaki, Terho] Univ Tampere, FIN-33101 Tampere, Finland.
[Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge CB2 1TN, England.
[Ouwehand, Willem H.] Wellcome Trust Sanger Inst, Cambridge, England.
[Ouwehand, Willem H.] NHS Blood & Transplant, Cambridge, England.
[Maerz, Winfried] Synlab Acad, Mannheim, Germany.
[Maerz, Winfried] Heidelberg Univ, Mannheim Inst Publ Hlth, Mannheim Med Fac, Social & Prevent Med, Mannheim, Germany.
[Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Jaervelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Biostat & Epidemiol, Sch Publ Hlth, MRC HPA Ctr Environm & Hlth,Fac Med, London, England.
[Jaervelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Children Young People & Families, Oulu, Finland.
[Whittaker, John C.] Univ London London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1E 7HT, England.
[Whittaker, John C.] GlaxoSmithKline, Quantitat Sci, Stevenage, Herts, England.
[Hingorani, Aroon D.] UCL, Div Populat Hlth, Dept Epidemiol & Publ Hlth, Genet Epidemiol Grp, London, England.
[Hingorani, Aroon D.] UCL, Div Med, Ctr Clin Pharmacol, London, England.
RP Vimaleswaran, KS (reprint author), UCL Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England.
EM e.hypponen@ucl.ac.uk
RI Smith, Albert Vernon/K-5150-2015; Aben, Katja/G-9686-2016; Rudan,
Igor/I-1467-2012; kinnunen, leena/B-7059-2012; Visvikis-Siest,
Sophie/H-2324-2014; Dunlop, Malcolm/F-1973-2011; Beckmann, Jacques S
/A-9772-2008; Kolcic, Ivana/E-2713-2017; Feitosa, Mary/K-8044-2012;
Ripatti, Samuli/H-9446-2014; Polasek, Ozren/B-6002-2011; Colaus,
PsyColaus/K-6607-2013; Meitinger, Thomas/O-1318-2015; Hypponen,
Elina/B-2596-2014; Theodoratou, Evropi/C-3430-2014; Kiemeney,
Lambertus/D-3357-2009; Aspelund, Thor/C-5983-2008; Palmer,
Lyle/K-3196-2014; Witte, Daniel/C-1722-2008; Lu, Chen/D-8514-2015;
Gudnason, Vilmundur/K-6885-2015;
OI Pichler, Irene/0000-0001-8251-0757; Magi, Reedik/0000-0002-2964-6011;
Lango Allen, Hana/0000-0002-7803-8688; Esko, Tonu/0000-0003-1982-6569;
Smith, Albert Vernon/0000-0003-1942-5845; Zgaga,
Lina/0000-0003-4089-9703; Dupuis, Josee/0000-0003-2871-3603;
Kritchevsky, Stephen/0000-0003-3336-6781; Luben,
Robert/0000-0002-5088-6343; Scherag, Andre/0000-0002-9406-4704;
Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Vandenput,
Liesbeth/0000-0002-1712-6131; Aben, Katja/0000-0002-0214-2147; Rudan,
Igor/0000-0001-6993-6884; kinnunen, leena/0000-0001-8739-4812;
Visvikis-Siest, Sophie/0000-0001-8104-8425; Dunlop,
Malcolm/0000-0002-3033-5851; Beckmann, Jacques S /0000-0002-9741-1900;
Kolcic, Ivana/0000-0001-7918-6052; Feitosa, Mary/0000-0002-0933-2410;
Thiering, Elisabeth/0000-0002-5429-9584; Kaakinen,
Marika/0000-0002-9228-0462; Karani, Vimal/0000-0002-8485-8930; Ripatti,
Samuli/0000-0002-0504-1202; Polasek, Ozren/0000-0002-5765-1862;
Hypponen, Elina/0000-0003-3670-9399; Theodoratou,
Evropi/0000-0001-5887-9132; Kiemeney, Lambertus/0000-0002-2368-1326;
Aspelund, Thor/0000-0002-7998-5433; Palmer, Lyle/0000-0002-1628-3055;
Witte, Daniel/0000-0002-0769-2922; Gudnason,
Vilmundur/0000-0001-5696-0084; Jorgensen, Torben/0000-0001-9453-2830;
Mitchell, Braxton/0000-0003-4920-4744; Ouwehand,
Willem/0000-0002-7744-1790; Lawlor, Debbie A/0000-0002-6793-2262;
Hattersley, Andrew/0000-0001-5620-473X; de Geus,
Eco/0000-0001-6022-2666; Kleber, Marcus/0000-0003-0663-7275
FU British Heart Foundation [PG/09/023]; UK Medical Research Council (MRC)
[G0601653]; British Heart Foundation Senior Research Fellow(Award)
[FS05/125]; MRC Centre of Epidemiology for Child Health; NHS Executive;
Canada Institute of Research (CIHR) Fellowship award; Amgen; Eli Lilly;
Medtronic; Merck; Novartis; Servier
FX The authors thank the British Heart Foundation (grant PG/09/023) and the
UK Medical Research Council (MRC; grant G0601653) for funding this work.
ADH is a British Heart Foundation Senior Research Fellow (Award
FS05/125). EH is a Department of Health (UK) Public Health Career
Scientist. This work was undertaken at the Centre for Paediatric
Epidemiology and Biostatistics, which benefits from funding support from
the MRC in its capacity as the MRC Centre of Epidemiology for Child
Health. Research at the University College London Institute of Child
Health and Great Ormond Street Hospital for Children NHS Trust benefits
from R&D funding received from the NHS Executive. No funding bodies had
any role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.; LTH is currently supported
by a Canada Institute of Research (CIHR) Fellowship award. CC has
received honoraria and consulting fees from Amgen, Eli Lilly, Medtronic,
Merck, Novartis, and Servier. WM is an employee of synlab laboratory
services GmbH. Synlab offers vitamin D testing. TJW is on the scientific
advisory board for Diasorin Inc. and has received research support from
them. JCW is 90% employed by GlaxoSmithKline (GSK) whilst maintaining a
10% appointment at London School of Hygiene & Tropical Medicine (LSHTM),
and holds GSK shares. All other authors declare that no competing
interests exist.
NR 50
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Z9 212
U1 4
U2 80
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1549-1676
J9 PLOS MED
JI PLos Med.
PD FEB
PY 2013
VL 10
IS 2
AR e1001383
DI 10.1371/journal.pmed.1001383
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 099BC
UT WOS:000315592800005
PM 23393431
ER
PT J
AU Ribeiro, AL
Sabino, EC
Marcolino, MS
Salemi, VMC
Ianni, BM
Fernandes, F
Nastari, L
Antunes, A
Menezes, M
Oliveira, CD
Sachdev, V
Carrick, DM
Busch, MP
Murphy, EL
AF Ribeiro, Antonio L.
Sabino, Ester C.
Marcolino, Milena S.
Salemi, Vera M. C.
Ianni, Barbara M.
Fernandes, Fabio
Nastari, Luciano
Antunes, Andre
Menezes, Marcia
Oliveira, Claudia Di Lorenzo
Sachdev, Vandana
Carrick, Danielle M.
Busch, Michael P.
Murphy, Eduard L.
CA NHLBI Retrovirus Epidemiology
TI Electrocardiographic Abnormalities in Trypanosoma cruzi Seropositive and
Seronegative Former Blood Donors
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID CHRONIC CHAGAS-DISEASE; VENTRICULAR SYSTOLIC DYSFUNCTION;
HEART-RATE-VARIABILITY; RISK STRATIFICATION; AUTONOMIC FUNCTION;
FOLLOW-UP; MORTALITY; POPULATION; BRAZIL; CARDIOMYOPATHY
AB Background: Blood donor screening leads to large numbers of new diagnoses of Trypanosoma cruzi infection, with most donors in the asymptomatic chronic indeterminate form. Information on electrocardiogram (ECG) findings in infected blood donors is lacking and may help in counseling and recognizing those with more severe disease. Objectives: To assess the frequency of ECG abnormalities in T. cruzi seropositive relative to seronegative blood donors, and to recognize ECG abnormalities associated with left ventricular dysfunction.
Methods: The study retrospectively enrolled 499 seropositive blood donors in Sao Paulo and Montes Claros, Brazil, and 483 seronegative control donors matched by site, gender, age, and year of blood donation. All subjects underwent a health clinical evaluation, ECG, and echocardiogram (Echo). ECG and Echo were reviewed blindly by centralized reading centers. Left ventricular (LV) dysfunction was defined as LV ejection fraction (EF), 0.50%.
Results: Right bundle branch block and left anterior fascicular block, isolated or in association, were more frequently found in seropositive cases (p<0.0001). Both QRS and QTc duration were associated with LVEF values (correlation coefficients -0.159, p<0.0003, and -0.142, p = 0.002) and showed a moderate accuracy in the detection of reduced LVEF (area under the ROC curve: 0.778 and 0.790, both p<0.0001). Several ECG abnormalities were more commonly found in seropositive donors with depressed LVEF, including rhythm disorders (frequent supraventricular ectopic beats, atrial fibrillation or flutter and pacemaker), intraventricular blocks (right bundle branch block and left anterior fascicular block) and ischemic abnormalities (possible old myocardial infarction and major and minor ST abnormalities). ECG was sensitive (92%) for recognition of seropositive donors with depressed LVEF and had a high negative predictive value (99%) for ruling out LV dysfunction.
Conclusions: ECG abnormalities are more frequent in seropositive than in seronegative blood donors. Several ECG abnormalities may help the recognition of seropositive cases with reduced LVEF who warrant careful follow-up and treatment.
C1 [Ribeiro, Antonio L.; Marcolino, Milena S.] Univ Fed Minas Gerais, Hosp Clin, Belo Horizonte, MG, Brazil.
[Ribeiro, Antonio L.; Marcolino, Milena S.] Univ Fed Minas Gerais, Fac Med, Belo Horizonte, MG, Brazil.
[Sabino, Ester C.] Univ Sao Paulo, Dept Infect Dis, Sao Paulo, Brazil.
[Sabino, Ester C.] Univ Sao Paulo, Inst Trop Med, Sao Paulo, Brazil.
[Salemi, Vera M. C.; Ianni, Barbara M.; Fernandes, Fabio; Nastari, Luciano] Univ Sao Paulo, Fac Med, Cardiomyopathy Unit, Heart Inst InCor, Sao Paulo, Brazil.
[Antunes, Andre; Menezes, Marcia] Univ Estadual Montes Claros, Ctr Ciencias Biol & Saude, Montes Claros, Brazil.
[Oliveira, Claudia Di Lorenzo] Univ Fed Sao Joao del Rei, Divinopolis, Brazil.
[Sachdev, Vandana] NHLBI, Bethesda, MD 20892 USA.
[Carrick, Danielle M.] WESTAT Corp, Rockville, MD 20850 USA.
[Busch, Michael P.; Murphy, Eduard L.] Blood Syst Res Inst, San Francisco, CA USA.
[Busch, Michael P.; Murphy, Eduard L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Ribeiro, AL (reprint author), Univ Fed Minas Gerais, Hosp Clin, Belo Horizonte, MG, Brazil.
EM tom@hc.ufmg.br
RI Ribeiro, Antonio/C-2707-2009; Nastari, Luciano/C-8528-2012; Fernandes,
Fabio/D-5994-2012; Sabino, Ester/F-7750-2010; Salemi, Vera/C-9104-2013;
Ianni, Barbara/C-7689-2012
OI Ribeiro, Antonio/0000-0002-2740-0042; Nastari,
Luciano/0000-0002-7959-3827; Sabino, Ester/0000-0003-2623-5126; Salemi,
Vera/0000-0002-7152-1810; Ianni, Barbara/0000-0002-1588-5492
FU NIH/NHLBI [HHSN268201100007I]
FX This study is part of NIH/NHLBI Retrovirus Epidemiology Donor Study-II
(REDS-II) - International Component, funded by the NIH/NHLBI (grant
HHSN268201100007I). ALR and ECS are researchers of the Brazilian
Research Agency (CNPq). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 49
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Z9 16
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD FEB
PY 2013
VL 7
IS 2
AR e2078
DI 10.1371/journal.pntd.0002078
PG 8
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 099TM
UT WOS:000315644900042
PM 23469305
ER
PT J
AU Guo, WP
Lin, XD
Wang, W
Tian, JH
Cong, ML
Zhang, HL
Wang, MR
Zhou, RH
Wang, JB
Li, MH
Xu, J
Holmes, EC
Zhang, YZ
AF Guo, Wen-Ping
Lin, Xian-Dan
Wang, Wen
Tian, Jun-Hua
Cong, Mei-Li
Zhang, Hai-Lin
Wang, Miao-Ruo
Zhou, Run-Hong
Wang, Jian-Bo
Li, Ming-Hui
Xu, Jianguo
Holmes, Edward C.
Zhang, Yong-Zhen
TI Phylogeny and Origins of Hantaviruses Harbored by Bats, Insectivores,
and Rodents
SO PLOS PATHOGENS
LA English
DT Article
ID SHREW SUNCUS-MURINUS; THOTTAPALAYAM VIRUS; MOLECULAR PHYLOGENY;
INFECTIOUS-DISEASES; NEWFOUND HANTAVIRUS; GENETIC DIVERSITY; EVOLUTION;
BIOGEOGRAPHY; DIVERGENT; MAMMALIA
AB Hantaviruses are among the most important zoonotic pathogens of humans and the subject of heightened global attention. Despite the importance of hantaviruses for public health, there is no consensus on their evolutionary history and especially the frequency of virus-host co-divergence versus cross-species virus transmission. Documenting the extent of hantavirus biodiversity, and particularly their range of mammalian hosts, is critical to resolving this issue. Here, we describe four novel hantaviruses (Huangpi virus, Lianghe virus, Longquan virus, and Yakeshi virus) sampled from bats and shrews in China, and which are distinct from other known hantaviruses. Huangpi virus was found in Pipistrellus abramus, Lianghe virus in Anourosorex squamipes, Longquan virus in Rhinolophus affinis, Rhinolophus sinicus, and Rhinolophus monoceros, and Yakeshi virus in Sorex isodon, respectively. A phylogenetic analysis of the available diversity of hantaviruses reveals the existence of four phylogroups that infect a range of mammalian hosts, as well as the occurrence of ancient reassortment events between the phylogroups. Notably, the phylogenetic histories of the viruses are not always congruent with those of their hosts, suggesting that cross-species transmission has played a major role during hantavirus evolution and at all taxonomic levels, although we also noted some evidence for virus-host co-divergence. Our phylogenetic analysis also suggests that hantaviruses might have first appeared in Chiroptera (bats) or Soricomorpha (moles and shrews), before emerging in rodent species. Overall, these data indicate that bats are likely to be important natural reservoir hosts of hantaviruses.
C1 [Guo, Wen-Ping; Wang, Wen; Cong, Mei-Li; Zhou, Run-Hong; Wang, Jian-Bo; Li, Ming-Hui; Xu, Jianguo; Zhang, Yong-Zhen] Chinese Ctr Dis Control & Prevent, Natl Inst Communicable Dis Control & Prevent, Dept Zoonoses, State Key Lab Infect Dis Prevent & Control, Beijing, Peoples R China.
[Lin, Xian-Dan] Wenzhou Ctr Dis Control & Prevent, Wenzhou, Zhejiang, Peoples R China.
[Tian, Jun-Hua] Wuhan Ctr Dis Control & Prevent, Wuhan, Hubei Province, Peoples R China.
[Zhang, Hai-Lin] Yunnan Inst Endem Dis Control & Prevent, Dali, Peoples R China.
[Wang, Miao-Ruo] Longquan Ctr Dis Control & Prevent, Longquan, Zhejiang, Peoples R China.
[Holmes, Edward C.] Univ Sydney, Sch Biol Sci, Sydney Emerging Infect & Biosecur Inst, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Guo, WP (reprint author), Chinese Ctr Dis Control & Prevent, Natl Inst Communicable Dis Control & Prevent, Dept Zoonoses, State Key Lab Infect Dis Prevent & Control, Beijing, Peoples R China.
EM zhangyongzhen@icdc.cn
RI Zhang, YZ/H-8101-2013;
OI Holmes, Edward/0000-0001-9596-3552
FU National Natural Science Foundation of China [81290343, 81273014]; State
Key Laboratory for Infection Disease Prevention and Control
[2011SKLID101]; Chinese Ministry of Science and Technology
[2003BA712A08-02]; National Institutes of Health [R01 GM080533-06]
FX This study was supported by National Natural Science Foundation of China
(Grants 81290343, 81273014), State Key Laboratory for Infection Disease
Prevention and Control (Grant 2011SKLID101), and the Chinese Ministry of
Science and Technology (Grant 2003BA712A08-02), and grant R01
GM080533-06 (to ECH) from the National Institutes of Health. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 61
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U1 4
U2 67
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 e1003159
DI 10.1371/journal.ppat.1003159
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 099UU
UT WOS:000315648900015
PM 23408889
ER
PT J
AU Hall, PR
Elmore, BO
Spang, CH
Alexander, SM
Manifold-Wheeler, BC
Castleman, MJ
Daly, SM
Peterson, MM
Sully, EK
Femling, JK
Otto, M
Horswill, AR
Timmins, GS
Gresham, HD
AF Hall, Pamela R.
Elmore, Bradley O.
Spang, Cynthia H.
Alexander, Susan M.
Manifold-Wheeler, Brett C.
Castleman, Moriah J.
Daly, Seth M.
Peterson, M. Michal
Sully, Erin K.
Femling, Jon K.
Otto, Michael
Horswill, Alexander R.
Timmins, Graham S.
Gresham, Hattie D.
TI Nox2 Modification of LDL Is Essential for Optimal Apolipoprotein
B-mediated Control of agr Type III Staphylococcus aureus Quorum-sensing
SO PLOS PATHOGENS
LA English
DT Article
ID LOW-DENSITY-LIPOPROTEIN; CHRONIC GRANULOMATOUS-DISEASE;
COMMUNITY-ASSOCIATED MRSA; ACCESSORY GENE REGULATOR; GUT-DERIVED
ENDOTOXIN; VIRULENCE DETERMINANTS; SINGLET OXYGEN; IN-VIVO; MONOCLONAL
AUTOANTIBODIES; HYPOCHLOROUS ACID
AB Staphylococcus aureus contains an autoinducing quorum-sensing system encoded within the agr operon that coordinates expression of virulence genes required for invasive infection. Allelic variation within agr has generated four agr specific groups, agr I-IV, each of which secretes a distinct autoinducing peptide pheromone (AIP1-4) that drives agr signaling. Because agr signaling mediates a phenotypic change in this pathogen from an adherent colonizing phenotype to one associated with considerable tissue injury and invasiveness, we postulated that a significant contribution to host defense against tissue damaging and invasive infections could be provided by innate immune mechanisms that antagonize agr signaling. We determined whether two host defense factors that inhibit AIP1-induced agrI signaling, Nox2 and apolipoprotein B (apoB), also contribute to innate control of AIP3-induced agrIII signaling. We hypothesized that apoB and Nox2 would function differently against AIP3, which differs from AIP1 in amino acid sequence and length. Here we show that unlike AIP1, AIP3 is resistant to direct oxidant inactivation by Nox2 characteristic ROS. Rather, the contribution of Nox2 to defense against agrIII signaling is through oxidation of LDL. ApoB in the context of oxLDL, and not LDL, provides optimal host defense against S. aureus agrIII infection by binding the secreted signaling peptide, AIP3, and preventing expression of the agr-driven virulence factors which mediate invasive infection. ApoB within the context of oxLDL also binds AIP 1-4 and oxLDL antagonizes agr signaling by all four agr alleles. Our results suggest that Nox2-mediated oxidation of LDL facilitates a conformational change in apoB to one sufficient for binding and sequestration of all four AIPs, demonstrating the interdependence of apoB and Nox2 in host defense against agr signaling. These data reveal a novel role for oxLDL in host defense against S. aureus quorum-sensing signaling.
C1 [Hall, Pamela R.; Elmore, Bradley O.; Spang, Cynthia H.; Manifold-Wheeler, Brett C.; Castleman, Moriah J.; Daly, Seth M.; Timmins, Graham S.] Univ New Mexico, Coll Pharm, San Francisco Joint Grad Grp Bioengn, Albuquerque, NM 87131 USA.
[Hall, Pamela R.; Spang, Cynthia H.; Alexander, Susan M.; Manifold-Wheeler, Brett C.; Daly, Seth M.; Peterson, M. Michal; Sully, Erin K.; Gresham, Hattie D.] New Mexico Vet Affairs Hlth Care Serv, Res Serv, Albuquerque, NM USA.
[Femling, Jon K.] Univ New Mexico, Dept Emergency Med, Albuquerque, NM 87131 USA.
[Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
[Horswill, Alexander R.] Univ Iowa, Dept Microbiol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA.
[Gresham, Hattie D.] Univ New Mexico, Sch Med, Dept Internal Med, Albuquerque, NM 87131 USA.
RP Hall, PR (reprint author), Univ New Mexico, Coll Pharm, San Francisco Joint Grad Grp Bioengn, Albuquerque, NM 87131 USA.
EM phall@salud.unm.edu
RI Hall, Pamela/O-5402-2016;
OI Hall, Pamela/0000-0003-2367-3382; timmins, graham/0000-0002-4971-718X;
Daly, Seth/0000-0002-3532-8810; Castleman, Moriah/0000-0001-7219-5044;
Otto, Michael/0000-0002-2222-4115
FU University of New Mexico & Cancer Center Fluorescence Microscopy Shared
Resource; NIH [AI090917, AI064926, AI078921]; National Institute of
Allergy and Infectious Diseases, NIH, ZIA [AI000904-10]; Department of
Veterans Affairs; University of New Mexico School of Medicine;
University of New Mexico [T32-AI007538]; Research Supplements to Promote
Diversity in Health-Related Research Program [AI091917-03S1]
FX We thank Dr. Richard S. Larson for use of critical equipment and
Genevieve Phillips for expert assistance in confocal microscopy. Images
in this paper were generated in the University of New Mexico & Cancer
Center Fluorescence Microscopy Shared Resource, funded as detailed at:
http://hsc.unm.edu/crtc/microscopy/Facility.html.; This work was
supported by NIH grants AI090917 (PRH), AI064926 (HDG), AI078921 (ARH),
the Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, NIH, ZIA AI000904-10 (MO), and by the Department of
Veterans Affairs (PRH, HDG). This project was also supported in part by
the Dedicated Health Research Funds of the University of New Mexico
School of Medicine allocated to the Signature Program in Cardiovascular
and Metabolic Disease (PRH). SMD was supported by the University of New
Mexico Biology of Infectious Diseases and Inflammation Training Grant
(T32-AI007538) and MJC was supported under the Research Supplements to
Promote Diversity in Health-Related Research Program (AI091917-03S1).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 104
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Z9 16
U1 0
U2 13
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 e1003166
DI 10.1371/journal.ppat.1003166
PG 16
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 099UU
UT WOS:000315648900019
PM 23459693
ER
PT J
AU Introini, A
Vanpouille, C
Lisco, A
Grivel, JC
Margolis, L
AF Introini, Andrea
Vanpouille, Christophe
Lisco, Andrea
Grivel, Jean-Charles
Margolis, Leonid
TI Interleukin-7 Facilitates HIV-1 Transmission to Cervico-Vaginal Tissue
ex vivo
SO PLOS PATHOGENS
LA English
DT Article
ID HUMAN LYMPHOID-TISSUE; VAGINAL EPITHELIAL-CELLS; BLOOD
MONONUCLEAR-CELLS; CD8(+) T-CELLS; SEXUAL TRANSMISSION; SEMINAL PLASMA;
HIV-1-INFECTED INDIVIDUALS; INFECTION; SEMEN; IL-7
AB The majority of HIV-1 infections in women occur through vaginal intercourse, in which virus-containing semen is deposited on the cervico-vaginal mucosa. Semen is more than a mere carrier of HIV-1, since it contains many biological factors, in particular cytokines, that may affect HIV-1 transmission. The concentration of interleukin (IL)-7, one of the most prominent cytokines in semen of healthy individuals, is further increased in semen of HIV-1-infected men. Here, we investigated the potential role of IL-7 in HIV-1 vaginal transmission in an ex vivo system of human cervico-vaginal tissue. We simulated an in vivo situation by depositing HIV-1 on cervico-vaginal tissue in combination with IL-7 at concentrations comparable with those measured in semen of HIV-1-infected individuals. We found that IL-7 significantly enhanced virus replication in ex vivo infected cervico-vaginal tissue. Similarly, we observed an enhancement of HIV-1 replication in lymphoid tissue explants. Analysis of T cells isolated from infected tissues showed that IL-7 reduced CD4(+) T cell depletion preventing apoptosis, as shown by the decrease in the number of cells expressing the apoptotic marker APO2.7 and the increase in the expression of the anti-apoptotic protein B-cell lymphoma (Bcl)-2. Also, IL-7 increased the fraction of cycling CD4(+) T cells, as evidenced by staining for the nuclear factor Ki-67. High levels of seminal IL-7 in vivo may be relevant to the survival of the founder pool of HIV-1-infected cells in the cervico-vaginal mucosa at the initial stage of infection, promoting local expansion and dissemination of HIV infection.
C1 [Introini, Andrea; Vanpouille, Christophe; Lisco, Andrea; Grivel, Jean-Charles; Margolis, Leonid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Introini, Andrea] Univ Milan, Dept Biomed Sci & Technol, I-20133 Milan, Italy.
RP Introini, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
EM margolis@helix.nih.gov
OI Introini, Andrea/0000-0002-9929-8964
FU National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institutes of Health. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 52
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Z9 22
U1 0
U2 5
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 e1003148
DI 10.1371/journal.ppat.1003148
PG 10
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 099UU
UT WOS:000315648900008
PM 23408885
ER
PT J
AU Nougairede, A
De Fabritus, L
Aubry, F
Gould, EA
Holmes, EC
de Lamballerie, X
AF Nougairede, Antoine
De Fabritus, Lauriane
Aubry, Fabien
Gould, Ernest A.
Holmes, Edward C.
de Lamballerie, Xavier
TI Random Codon Re-encoding Induces Stable Reduction of Replicative Fitness
of Chikungunya Virus in Primate and Mosquito Cells
SO PLOS PATHOGENS
LA English
DT Article
ID NUCLEOTIDE SUBSTITUTIONS; ENCEPHALITIS-VIRUS; INVERTEBRATE CELLS; CAPSID
PROTEIN; RNA VIRUSES; GENOME; EVOLUTION; OUTBREAK; REGION; USAGE
AB Large-scale codon re-encoding represents a powerful method of attenuating viruses to generate safe and cost-effective vaccines. In contrast to specific approaches of codon re-encoding which modify genome-scale properties, we evaluated the effects of random codon re-encoding on the re-emerging human pathogen Chikungunya virus (CHIKV), and assessed the stability of the resultant viruses during serial in cellulo passage. Using different combinations of three 1.4 kb randomly re-encoded regions located throughout the CHIKV genome six codon re-encoded viruses were obtained. Introducing a large number of slightly deleterious synonymous mutations reduced the replicative fitness of CHIKV in both primate and arthropod cells, demonstrating the impact of synonymous mutations on fitness. Decrease of replicative fitness correlated with the extent of re-encoding, an observation that may assist in the modulation of viral attenuation. The wild-type and two re-encoded viruses were passaged 50 times either in primate or insect cells, or in each cell line alternately. These viruses were analyzed using detailed fitness assays, complete genome sequences and the analysis of intra-population genetic diversity. The response to codon re-encoding and adaptation to culture conditions occurred simultaneously, resulting in significant replicative fitness increases for both re-encoded and wild type viruses. Importantly, however, the most re-encoded virus failed to recover its replicative fitness. Evolution of these viruses in response to codon re-encoding was largely characterized by the emergence of both synonymous and non-synonymous mutations, sometimes located in genomic regions other than those involving re-encoding, and multiple convergent and compensatory mutations. However, there was a striking absence of codon reversion (<0.4%). Finally, multiple mutations were rapidly fixed in primate cells, whereas mosquito cells acted as a brake on evolution. In conclusion, random codon re-encoding provides important information on the evolution and genetic stability of CHIKV viruses and could be exploited to develop a safe, live attenuated CHIKV vaccine.
C1 [Nougairede, Antoine; De Fabritus, Lauriane; Aubry, Fabien; Gould, Ernest A.; de Lamballerie, Xavier] Aix Marseille Univ, EHESP French Sch Publ Hlth, IRD French Inst Res Dev, UMR D Emergence Pathol Virales 190, Marseille, France.
[Holmes, Edward C.] Univ Sydney, Sch Biol Sci, Sydney Emerging Infect & Biosecur Inst, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Nougairede, A (reprint author), Aix Marseille Univ, EHESP French Sch Publ Hlth, IRD French Inst Res Dev, UMR D Emergence Pathol Virales 190, Marseille, France.
EM antoine.nougairede@univ-amu.fr
OI de Fabritus, Lauriane/0000-0003-0668-4629; Holmes,
Edward/0000-0001-9596-3552
FU Aix-Marseille University
FX This work was supported by Aix-Marseille University. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 66
TC 14
Z9 14
U1 0
U2 5
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 e1003172
DI 10.1371/journal.ppat.1003172
PG 18
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 099UU
UT WOS:000315648900023
PM 23436995
ER
PT J
AU Leung, JM
Olivier, KN
AF Leung, Janice M.
Olivier, Kenneth N.
TI Nontuberculous Mycobacteria in Patients with Cystic Fibrosis
SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Review
DE cystic fibrosis; nontuberculous mycobacteria; mycobacterium infections;
Mycobacterium avium complex; Mycobacterium abscessus
ID LUNG-TRANSPLANT RECIPIENTS; FATAL PULMONARY INFECTION;
ACETYL-L-CYSTEINE; AVIUM COMPLEX; ABSCESSUS INFECTION;
PSEUDOMONAS-AERUGINOSA; MULTICENTER PREVALENCE; DECONTAMINATION METHOD;
SODIUM HYDROXIDE; SPUTUM SAMPLES
AB As a result of their underlying lung disease, patients with cystic fibrosis (CF) have a higher risk of developing nontuberculous mycobacteria (NTM) infections compared with the general population. Although NTM may be present intermittently in low amounts in the airways of CF patients without an apparent clinical effect, progressive respiratory decline due to NTM disease may also occur. Identifying this latter group of patients can be challenging for clinicians because the usual symptoms exhibited by infected individuals without CF may be difficult to distinguish from the baseline respiratory dysfunction of a patient with CF. The distinction, however, is of utmost importance because those patients with clinical worsening may benefit considerably from antimycobacterial treatment. For CF patients under evaluation for lung transplantation, NTM can play a critical role in determining overall outcomes, and treatment in the pre- and post-transplant period may be vital to success. A general approach to NTM in CF thus involves surveillance to detect NTM, careful monitoring for associated clinical decline, and consideration of treatment given for those with an otherwise unexplained deterioration. In this review, the epidemiology and clinical course of NTM in CF is described with an algorithm for management proposed.
C1 [Leung, Janice M.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Olivier, Kenneth N.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Leung, JM (reprint author), NIH, Dept Crit Care Med, 10 Ctr Dr,Rm 2C145, Bethesda, MD 20892 USA.
EM Janice.leung@nih.gov
FU Division of Intramural Research; National Institute of Allergy and
Infectious Diseases; National Institutes of Health Clinical Center
FX This work was supported in part by the Division of Intramural Research,
the National Institute of Allergy and Infectious Diseases, and the
National Institutes of Health Clinical Center.
NR 130
TC 19
Z9 19
U1 0
U2 15
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1069-3424
J9 SEMIN RESP CRIT CARE
JI Semin. Respir. Crit. Care Med.
PD FEB
PY 2013
VL 34
IS 1
BP 124
EP 134
DI 10.1055/s-0033-1333574
PG 11
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 101RY
UT WOS:000315793300012
PM 23460012
ER
PT J
AU Fuhrman, BJ
Freedman, DM
Bhatti, P
Doody, MM
Fu, YP
Chang, SC
Linet, MS
Sigurdson, AJ
AF Fuhrman, Barbara J.
Freedman, D. Michal
Bhatti, Parveen
Doody, Michele M.
Fu, Yi-Ping
Chang, Shih-Chen
Linet, Martha S.
Sigurdson, Alice J.
TI Sunlight, Polymorphisms of Vitamin D-related Genes and Risk of Breast
Cancer
SO ANTICANCER RESEARCH
LA English
DT Article
DE Vitamin D; sunlight; polymorphisms; breast cancer; gene; case-control
ID US RADIOLOGIC TECHNOLOGISTS; PROSTATE-CANCER; UNITED-STATES; EXPOSURE;
ASSOCIATION; RADIATION; VARIANTS; MORTALITY; CYP27B1; CYP24A1
AB Background/Aim: Geographic gradients in breast cancer incidence and mortality suggest that vitamin D may reduce risk. The enzyme 25-hydroxyvitamin D 24-hydroxylase (CYP24A1), which degrades the active form of vitamin D, and the vitamin D receptor (VDR) are both found in breast tissue. We investigated six polymorphisms in CYP24A1 and two in the VDR gene in association with breast cancer risk. Materials and Methods: We conducted a case control study within the nationwide U.S. Radiologic Technologists cohort, including 845 controls and 484 incident breast cancer cases. Associations of polymorphic variants and ecologic and personal measures of sun exposure with breast cancer risk were assessed using unconditional logistic regression. Results: Two polymorphisms in CYP24A1 were associated with increased breast cancer risk (rs34043203, P-trend=0.03; rs2762934, P-trend=0.005) and one with reduced breast cancer risk (rs1570669, P-trend=0.048). Risk was inversely associated with minor alleles for the VDR Bsm1 polymorphism (rs1544410, P-trend=0.05) but not Fok1 (rs2228570). Sunlight measures were not associated with breast cancer risk, however significant interactions between time outdoors in the teen years and three unlinked genotypes were found for VDR (rs1544410, rs2228570) and CYP24A1 (rs1570669). Conclusion: In this nation-wide breast cancer case-control study, we found that the vitamin D pathway was involved in disease etiology and our results further suggest that reduced cancer risk, in association with sunlight, may depend on timing of exposure and genetic background. These findings merit further investigation.
C1 [Fuhrman, Barbara J.; Freedman, D. Michal; Doody, Michele M.; Linet, Martha S.; Sigurdson, Alice J.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Bhatti, Parveen] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Fu, Yi-Ping] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Gaithersburg, MD USA.
[Chang, Shih-Chen] Genentic Inc, Patient Reported Outcomes & Healthcare Data Strat, Epidemiol, San Francisco, CA USA.
RP Sigurdson, AJ (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd MSC 7238, Bethesda, MD 20892 USA.
EM sigurdsa@mail.nih.gov
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX We are grateful to the radiologic technologists who participated in the
U.S. Radio logic Technologists Study; Jerry Reid of the American
Registry of Radio logic Technologists for continued support of this
study; Diane Kampa and Allison Iwan of the University of Minnesota for
data collection and study coordination; Laura Bowen of Information
Management Systems for biomedical computing statistical support. This
research was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, 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.
NR 29
TC 20
Z9 20
U1 0
U2 8
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
J9 ANTICANCER RES
JI Anticancer Res.
PD FEB
PY 2013
VL 33
IS 2
BP 543
EP 551
PG 9
WC Oncology
SC Oncology
GA 096SG
UT WOS:000315424000025
PM 23393347
ER
PT J
AU Tsiouli, E
Alexopoulos, EC
Stefanaki, C
Darviri, C
Chrousos, GP
AF Tsiouli, Elina
Alexopoulos, Evangelos C.
Stefanaki, Charikleia
Darviri, Christina
Chrousos, George P.
TI Effects of diabetes-related family stress on glycemic control in young
patients with type 1 diabetes Systematic review
SO CANADIAN FAMILY PHYSICIAN
LA English
DT Review
DE diabetes type 1; glycemic control; family stress; family conflict;
family function
ID QUALITY-OF-LIFE; METABOLIC-CONTROL; PSYCHOLOGICAL CARE; CHILDREN;
ADOLESCENTS; MELLITUS; ADHERENCE; ENVIRONMENT; MANAGEMENT; PREDICTORS
AB Objective To investigate the way that family stress influences glycemic control among patients with diabetes who are younger than 18 years of age.
Data sources PubMed and Scopus were searched for relevant studies published since 1990 using the following key words: diabetes type 1, glycemic control, family stress, family conflict, and family function.
Study selection In total, 1478 papers were identified in the initial search. The final review included 6 cohort studies, 3 cross-sectional studies, and 1 qualitative review in which family stress was assessed using specific diabetes-related conflict measurement instruments, and glycemic control was evaluated by glycosylated hemoglobin measurement.
Synthesis In most studies family stress was negatively correlated with patients' glycemic control. Family function was strongly related to patients' glycemic control, while family conflict was adversely associated with glycemic control. Families of low socioeconomic status, those of adolescents with diabetes, and those of single parents were more prone to diabetes-related stress and thus more susceptible to worse glycemic control.
Conclusion Therapeutic psychological interventions and educational programs can help alleviate family diabetes-related stress and will likely improve glycemic control.
C1 [Alexopoulos, Evangelos C.; Darviri, Christina] Univ Athens, Sch Med, GR-10679 Athens, Greece.
[Chrousos, George P.] Univ Athens, Sch Med, Dept Pediat 1, GR-10679 Athens, Greece.
[Chrousos, George P.] UNESCO Chair Adolescent Hlth Care, Div Endocrinol Diabet & Metab, Delft, Netherlands.
[Chrousos, George P.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Darviri, C (reprint author), Acad Athens, Biomed Res Fdn, Soranou Ephessiou Str 4, GR-11527 Athens, Greece.
EM cdarviri@yahoo.gr
RI Alexopoulos, Evangelos/C-4730-2008
OI Alexopoulos, Evangelos/0000-0003-0449-918X
NR 30
TC 17
Z9 17
U1 8
U2 30
PU COLL FAMILY PHYSICIANS CANADA
PI MISSISSAUGA
PA 2630 SKYMARK AVE, MISSISSAUGA, ONTARIO L4W 5A4, CANADA
SN 0008-350X
J9 CAN FAM PHYSICIAN
JI Can. Fam. Phys.
PD FEB
PY 2013
VL 59
IS 2
BP 143
EP 149
PG 7
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA 093QW
UT WOS:000315207500013
PM 23418238
ER
PT J
AU Ruiz-Narvaez, EA
Rosenberg, L
Yao, S
Rotimi, CN
Cupples, AL
Bandera, EV
Ambrosone, CB
Adams-Campbell, LL
Palmer, JR
AF Ruiz-Narvaez, Edward A.
Rosenberg, Lynn
Yao, Song
Rotimi, Charles N.
Cupples, Adrienne L.
Bandera, Elisa V.
Ambrosone, Christine B.
Adams-Campbell, Lucile L.
Palmer, Julie R.
TI Fine-mapping of the 6q25 locus identifies a novel SNP associated with
breast cancer risk in African-American women
SO CARCINOGENESIS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; UNRELATED INDIVIDUALS;
ADMIXTURE; REPLICATION; POPULATIONS; ANCESTRY; LINKAGE; SAMPLES; HEALTH
AB The rs2046210 single nucleotide polymorphism (SNP) in the 6q25.1 region was identified in a breast cancer genome-wide association study of Chinese women. The SNP has been replicated in European ancestry populations, but replication efforts have failed in African ancestry populations. We evaluated a total of 13 tagging SNPs in the linkage disequilibrium block around rs2046210 in a case-control study of breast cancer nested within the Black Women's Health Study, which included 1191 cases and 1941 controls. Replication of initial significant findings was carried out in 665 cases and 821 controls of African ancestry from the Women's Circle of Health Study (WCHS). No significant association was found for rs2046210 in univariate analysis. A new SNP, rs2046211, was significantly associated with reduced risk of breast cancer and was replicated in data from WCHS. In joint analyses that included both SNPs, the rs2046210-A allele was associated with increased risk of breast cancer [ odds ratio (OR) = 1.14; 95% confidence interval (CI) = 1.02-1.28], and the rs2046211-G allele was associated with reduced risk (OR = 0.80; 95% CI = 0.67-0.95). Haplotype analysis confirmed these results and showed that the rs2046210-A allele is present in high-risk (rs2046211-C/rs2046210-A) and low-risk (rs2046211-G/rs2046210-A) haplo-types. Our results confirm the importance of 6q25.1 as a breast cancer susceptibility region. We replicated the rs2046210 association, after accounting for the haplotype background that included rs2046211 in African-American women, and we report the presence of a novel signal that is tagged by rs2046211.
C1 [Ruiz-Narvaez, Edward A.; Rosenberg, Lynn; Palmer, Julie R.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
[Ruiz-Narvaez, Edward A.; Rosenberg, Lynn; Palmer, Julie R.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
[Yao, Song; Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Cupples, Adrienne L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Bandera, Elisa V.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ 08903 USA.
[Adams-Campbell, Lucile L.] Georgetown Univ, Med Ctr, Washington, DC 20057 USA.
RP Ruiz-Narvaez, EA (reprint author), Boston Univ, Slone Epidemiol Ctr, 1010 Commonwealth Ave, Boston, MA 02215 USA.
EM eruiznar@bu.edu
RI Bandera, Elisa/M-4169-2014;
OI Bandera, Elisa/0000-0002-8789-2755; Ruiz-Narvaez,
Edward/0000-0002-0339-5824; Palmer, Julie/0000-0002-6534-335X
FU National Institutes of Health [R01 CA058420, R01 CA098663, R01
CA100598]; Susan G. Komen for the Cure Foundation; United States Army
Medical Research and Material Command [DAMD-17-01-1-0334]; National
Cancer Institute [P01 CA151135, K22 CA138563]
FX National Institutes of Health (R01 CA058420 and R01 CA098663); and the
Susan G. Komen for the Cure Foundation. The WCHS is supported by grants
from National Institutes of Health (R01 CA100598); United States Army
Medical Research and Material Command (DAMD-17-01-1-0334). The research
teams of both BWHS and WCHS are also supported by the National Cancer
Institute (P01 CA151135). National Cancer Institute (K22 CA138563 to
E.V.B.).
NR 22
TC 6
Z9 6
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD FEB
PY 2013
VL 34
IS 2
BP 287
EP 291
DI 10.1093/carcin/bgs334
PG 5
WC Oncology
SC Oncology
GA 099NH
UT WOS:000315627900006
PM 23104177
ER
PT J
AU Mao, KR
Chen, SZ
Chen, MK
Ma, YL
Wang, Y
Huang, B
He, ZY
Zeng, Y
Hu, Y
Sun, SH
Li, J
Wu, XD
Wang, XR
Strober, W
Chen, C
Meng, GX
Sun, B
AF Mao, Kairui
Chen, Shuzhen
Chen, Mingkuan
Ma, Yonglei
Wang, Yan
Huang, Bo
He, Zhengyu
Zeng, Yan
Hu, Yu
Sun, Shuhui
Li, Jing
Wu, Xiaodong
Wang, Xiangrui
Strober, Warren
Chen, Chang
Meng, Guangxun
Sun, Bing
TI Nitric oxide suppresses NLRP3 inflammasome activation and protects
against LPS-induced septic shock
SO CELL RESEARCH
LA English
DT Article
DE nitric oxide; NLRP3 inflammasome; septic shock
ID NALP3 INFLAMMASOME; IMMUNE-RESPONSES; MESSENGER-RNA; HOST-DEFENSE;
SYNTHASE; MICE; EXPRESSION; DISEASE; CELLS; NITROSYLATION
AB Inflammasomes are multi-protein complexes that trigger the activation of caspase-1 and the maturation of interleukin-1 beta (IL-1 beta), yet the regulation of these complexes remains poorly characterized. Here we show that nitric oxide (NO) inhibited the NLRP3-mediated ASC pyroptosome formation, caspase-1 activation and IL-1 beta secretion in myeloid cells from both mice and humans. Meanwhile, endogenous NO derived from iNOS (inducible form of NO synthase) also negatively regulated NLRP3 inflammasome activation. Depletion of iNOS resulted in increased accumulation of dysfunctional mitochondria in response to LPS and ATP, which was responsible for the increased IL-1 beta production and caspase-1 activation. iNOS deficiency or pharmacological inhibition of NO production enhanced NLRP3-dependent cytokine production in vivo, thus increasing mortality from LPS-induced sepsis in mice, which was prevented by NLRP3 deficiency. Our results thus identify NO as a critical negative regulator of the NLRP3 inflammasome via the stabilization of mitochondria. This study has important implications for the design of new strategies to control NLRP3-related diseases.
C1 [Mao, Kairui; Chen, Shuzhen; Hu, Yu; Wu, Xiaodong; Sun, Bing] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.
[Chen, Mingkuan; Ma, Yonglei; Wang, Yan; Zeng, Yan; Meng, Guangxun; Sun, Bing] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai 200025, Peoples R China.
[Huang, Bo; Chen, Chang] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
[He, Zhengyu; Wang, Xiangrui] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Anesthesiol, Shanghai 200127, Peoples R China.
[Sun, Shuhui] Fudan Univ, Sch Med, Shanghai 200032, Peoples R China.
[Li, Jing] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Informat Ctr Life Sci, Shanghai 200031, Peoples R China.
[Strober, Warren] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
RP Sun, B (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.
EM changchen@moon.ibp.ac.cn; gxmeng@sibs.ac.cn; bsun@sibs.ac.cn
RI huang, bo/B-4649-2008;
OI Hu, Yu/0000-0002-9511-9383; huang, bo/0000-0001-5945-7601; 孟,
广勋/0000-0002-4253-9675
FU National Basic Research Program of China (973 program) [2013CB530504];
National Natural Science Foundation of China [31230024, 31030029,
31100662, 31030023, 91029707, 31170868]; Shanghai Natural Science
Foundation [11ZR1442600]; National Ministry of Science and Technology
[2007DFC31700]; National Science and Technology Major Project
[2008ZX10004-002, 2008ZX10002-014, 2009ZX10004-105, 2009ZX10004-016,
2011ZX10004-001, 2012ZX10002007]; Shanghai Pasteur Health Research
Foundation [SPHRF2008001, SPHRF2009001]; SA-SIBS Discovery Innovation
Grant; Li Kha Shing Foundation; 100 Talent Program of Chinese Academy of
Sciences
FX We thank R Caspi (National Eye Institute, NIH, USA) and D Li (Shanghai
Institutes for Biological Sciences, China) for helpful comments, and S
Skinner for critical reading of the manuscript. This work was supported
by the National Basic Research Program of China (973 program,
2013CB530504), the National Natural Science Foundation of China
(31230024, 31030029, 31100662, 31030023, 91029707, 31170868), the
Shanghai Natural Science Foundation (11ZR1442600), the National Ministry
of Science and Technology (2007DFC31700), the National Science and
Technology Major Project (2008ZX10004-002, 2008ZX10002-014,
2009ZX10004-105, 2009ZX10004-016, 2011ZX10004-001 and 2012ZX10002007),
the Shanghai Pasteur Health Research Foundation (SPHRF2008001 and
SPHRF2009001), the SA-SIBS Discovery Innovation Grant, the Li Kha Shing
Foundation and the 100 Talent Program of the Chinese Academy of Sciences
(to GM).
NR 50
TC 91
Z9 101
U1 6
U2 41
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
EI 1748-7838
J9 CELL RES
JI Cell Res.
PD FEB
PY 2013
VL 23
IS 2
BP 201
EP 212
DI 10.1038/cr.2013.6
PG 12
WC Cell Biology
SC Cell Biology
GA 096TE
UT WOS:000315426400009
PM 23318584
ER
PT J
AU Chen, SY
Li, H
Gaudenz, K
Paulson, A
Guo, FL
Trimble, R
Peak, A
Seidel, C
Deng, CX
Furuta, Y
Xie, T
AF Chen, Shuyi
Li, Hua
Gaudenz, Karin
Paulson, Ariel
Guo, Fengli
Trimble, Rhonda
Peak, Allison
Seidel, Christopher
Deng, Chuxia
Furuta, Yasuhide
Xie, Ting
TI Defective FGF signaling causes coloboma formation and disrupts retinal
neurogenesis
SO CELL RESEARCH
LA English
DT Article
DE optic fissure; coloboma; FGF signaling; retinal ganglion cells
ID FIBROBLAST GROWTH-FACTORS; OPTIC FISSURE CLOSURE; EYE MORPHOGENESIS;
VERTEBRATE RETINA; NEURAL RETINA; DROSOPHILA GASTRULATION; TARGETED
DISRUPTION; PATTERNING DEFECTS; MOUSE GASTRULATION; PAX2 EXPRESSION
AB The optic fissure (OF) is a transient opening on the ventral side of the developing vertebrate eye that closes before nearly all retinal progenitor cell differentiation has occurred. Failure to close the OF results in coloboma, a congenital disease that is a major cause of childhood blindness. Although human genetic studies and animal models have linked a number of genes to coloboma, the cellular and molecular mechanisms driving the closure of the OF are still largely unclear. In this study, we used Cre-LoxP-mediated conditional removal of fibroblast growth factor (FGF) receptors, Fgfr1 and Fgfr2, from the developing optic cup (OC) to show that FGF signaling regulates the closing of the OF. Our molecular, cellular and transcriptome analyses of Fgfr1 and Fgfr2 double conditional knockout OCs suggest that FGF signaling controls the OF closure through modulation of retinal progenitor cell proliferation, fate specification and morphological changes. Furthermore, Fgfr1 and Fgfr2 double conditional mutant retinal progenitor cells fail to initiate retinal ganglion cell (RGC) genesis. Taken together, our mouse genetic studies reveal that FGF signaling is essential for OF morphogenesis and RGC development.
C1 [Chen, Shuyi; Li, Hua; Gaudenz, Karin; Paulson, Ariel; Guo, Fengli; Trimble, Rhonda; Peak, Allison; Seidel, Christopher; Xie, Ting] Stowers Inst Med Res, Kansas City, MO 64110 USA.
[Chen, Shuyi; Xie, Ting] Univ Kansas, Sch Med, Dept Anat & Cell Biol, Kansas City, KS 66160 USA.
[Deng, Chuxia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Furuta, Yasuhide] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
RP Chen, SY (reprint author), Stowers Inst Med Res, 1000 E 50th St, Kansas City, MO 64110 USA.
EM sch@stowers.org
RI deng, chuxia/N-6713-2016
FU SIMR; MR and Evelyn Hudson Foundation; NIH [EY012128]
FX We would like to thank D Ornitz for the Fgfr2 conditional allele, B
Sandersan for help in qPCR experiments, R Krumlauf, W Neaves, M Lewallen
and C Tanzie for comments, the Xie laboratory members for stimulating
discussions, the Laboratory Animal Services Facility at SIMR for
maintaining our mouse strains, and C Flournoy for administrative
assistance. This work was supported by SIMR (T Xie), the MR and Evelyn
Hudson Foundation (T Xie), and NIH grant (EY012128, Y Furuta).
NR 97
TC 7
Z9 7
U1 0
U2 10
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
J9 CELL RES
JI Cell Res.
PD FEB
PY 2013
VL 23
IS 2
BP 254
EP 273
DI 10.1038/cr.2012.150
PG 20
WC Cell Biology
SC Cell Biology
GA 096TE
UT WOS:000315426400013
PM 23147794
ER
PT J
AU Rana, R
Coulter, S
Kinyamu, H
Goldstein, JA
AF Rana, Ritu
Coulter, Sherry
Kinyamu, Harriet
Goldstein, Joyce A.
TI RBCK1, an E3 Ubiquitin Ligase, Interacts with and Ubiquinates the Human
Pregnane X Receptor
SO DRUG METABOLISM AND DISPOSITION
LA English
DT Article
ID CONSTITUTIVE ANDROSTANE RECEPTOR; CYP3A4 GENE-EXPRESSION; NUCLEAR
RECEPTOR; SIGNALING PATHWAY; HUMAN HEPATOCYTES; BINDING PROTEIN;
CROSS-TALK; PXR; INDUCTION; IDENTIFICATION
AB The pregnane X receptor (PXR, NR1I2) plays a pivotal role in the disposition and detoxification of numerous foreign and endogenous chemicals by increasing transcription of numerous target genes, including phase I and II drug-metabolizing enzymes and transporters. In the present study, yeast two-hybrid screening identified an E3 ubiquitin ligase, RBCK1 (Ring-B-box-coiled-coil protein interacting with protein kinase C-1), as a human pregnane X receptor (hPXR)-interacting protein. Coimmunoprecipitation studies confirmed the interaction between RBCK1 and hPXR when both were ectopically expressed in AD-293 cells. Domain mapping studies showed that the interaction between RBCK1 and hPXR involves all RBCK1 domains. We further demonstrate that RBCK1 ubiquitinates hPXR, and this may target hPXR for degradation by the ubiquitin-proteasome pathway. Simultaneous ectopic overexpression of RBCK1 and PXR decreased PXR levels in AD-293 cells, and this decrease was inhibited by the proteasomal inhibitor MG-132 (carbobenzoxy-Leu-Leu-leucinal). Furthermore, overexpression of RBCK1 decreased endogenous levels of PXR in HepG2 cells. Of importance, ectopic overexpression and silencing of endogenous RBCK1 in primary human hepatocytes resulted in a decrease and increase, respectively, in endogenous PXR protein levels and in the induction of PXR target genes by rifampicin. These results suggest that RBCK1 is important for the ubiquitination of PXR and may play a role in its proteasomal degradation.
C1 [Rana, Ritu; Coulter, Sherry; Goldstein, Joyce A.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Kinyamu, Harriet] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Goldstein, JA (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM goldste1@niehs.nih.gov
OI Coulter, Sherry/0000-0002-2732-3470
FU Intramural Research Program of the National Institutes of Health
National Institute of Environmental Health Sciences [Z01ES02124,
Z01ES071006-12]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health National Institute of Environmental Health
Sciences [Grants Z01ES02124 and Z01ES071006-12].
NR 43
TC 9
Z9 10
U1 0
U2 3
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0090-9556
J9 DRUG METAB DISPOS
JI Drug Metab. Dispos.
PD FEB
PY 2013
VL 41
IS 2
BP 398
EP 405
DI 10.1124/dmd.112.048728
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 095RO
UT WOS:000315352400019
PM 23160820
ER
PT J
AU Johnson, CH
Bonzo, JA
Cheng, J
Krausz, KW
Kang, DW
Luecke, H
Idle, JR
Gonzalez, FJ
AF Johnson, Caroline H.
Bonzo, Jessica A.
Cheng, Jie
Krausz, Kristopher W.
Kang, Dong Wook
Luecke, Hans
Idle, Jeffrey R.
Gonzalez, Frank J.
TI Cytochrome P450 Regulation by alpha-Tocopherol in Pxr-Null and
PXR-Humanized Mice
SO DRUG METABOLISM AND DISPOSITION
LA English
DT Article
ID PREGNANE-X-RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; HUMAN CYP2C
GENES; HEPG2 CELLS; ACTIVE/ANDROSTANE RECEPTOR; TRANSCRIPTIONAL
REGULATION; PHENYTOIN INDUCTION; OMEGA-HYDROXYLASE; DRUG-INTERACTIONS;
CYP3A INDUCTION
AB The pregnane X receptor (PXR) has been postulated to play a role in the metabolism of alpha-tocopherol owing to the up-regulation of hepatic cytochrome P450 (P450) 3A in human cell lines and murine models after alpha-tocopherol treatment. However, in vivo studies confirming the role of PXR in alpha-tocopherol metabolism in humans presents significant difficulties and has not been performed. PXR-humanized (hPXR), wildtype, and Pxr-null mouse models were used to determine whether alpha-tocopherol metabolism is influenced by species-specific differences in PXR function in vivo. No significant difference in the concentration of the major alpha-tocopherol metabolites was observed among the hPXR, wild-type, and Pxr-null mice through mass spectrometry-based metabolomics. Gene expression analysis revealed significantly increased expression of Cyp3a11 as well as several other P450s only in wild-type mice, suggesting species-specificity for alpha-tocopherol activation of PXR. Luciferase reporter assay confirmed activation of mouse PXR by alpha-tocopherol. Analysis of the Cyp2c family of genes revealed increased expression of Cyp2c29, Cyp2c37, and Cyp2c55 in wild-type, hPXR, and Pxr-null mice, which suggests PXR-independent induction of Cyp2c gene expression. This study revealed that alpha-tocopherol is a partial agonist of PXR and that PXR is necessary for Cyp3a induction by alpha-tocopherol. The implications of a novel role for alpha-tocopherol in Cyp2c gene regulation are also discussed.
C1 [Johnson, Caroline H.; Bonzo, Jessica A.; Cheng, Jie; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kang, Dong Wook; Luecke, Hans] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Idle, Jeffrey R.] Univ Bern, Hepatol Res Grp, Dept Clin Res, Bern, Switzerland.
RP Gonzalez, FJ (reprint author), NCI, Bldg 37,Room 3106, Bethesda, MD 20892 USA.
EM fjgonz@helix.nih.gov
FU Intramural Research Program of the National Institutes of Health
National Cancer Institute [1ZIABC005562-24]; National Institutes of
Health Office of Dietary Supplements
FX This work was supported by the Intramural Research Program of the
National Institutes of Health National Cancer Institute [Grant
1ZIABC005562-24]; and an intramural award from the National Institutes
of Health Office of Dietary Supplements (C.H.J.).
NR 40
TC 4
Z9 5
U1 1
U2 7
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0090-9556
J9 DRUG METAB DISPOS
JI Drug Metab. Dispos.
PD FEB
PY 2013
VL 41
IS 2
BP 406
EP 413
DI 10.1124/dmd.112.048009
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 095RO
UT WOS:000315352400020
PM 23160821
ER
PT J
AU Merikangas, KR
AF Merikangas, Kathleen R.
TI Contributions of Epidemiology to Our Understanding of Migraine
SO HEADACHE
LA English
DT Review
DE epidemiology; incidence; migraine; second edition of the International
Classification of Headache Disorders-2; adult; children
ID TENSION-TYPE HEADACHE; GENOME-WIDE ASSOCIATION; GERMAN DMKG HEADACHE;
HIGH-SCHOOL STUDENTS; UNITED-STATES; FOLLOW-UP; EUROLIGHT PROJECT;
INTERNATIONAL CLASSIFICATION; CLINICAL CHARACTERISTICS; REPRESENTATIVE
SAMPLE
AB Background During the past decade, the introduction of the second edition of the International Classification of Headache Disorders (ICHD-II) and the initiation of active campaigns to increase awareness of the high magnitude, burden, and impact of migraine have stimulated numerous studies of population-based data on the prevalence, correlates, and impact of migraine. Objective This paper provides an update of the literature on the worldwide epidemiology of migraine from studies that included the ICHD-II criteria. The aims of this paper are: (1) to review evidence regarding the magnitude of migraine; (2) to summarize information on the correlates and impact of migraine; and (3) to discuss the contributions, challenges, and future directions in the epidemiology of migraine. Evidence on the magnitude of migraine is divided into the following types of data: (1) prevalence rates of ICHD-II-defined migraine and tension-type headache from international population-based studies of adults; (2) the magnitude of migraine in U.S. studies; (3) ICHD-II-based international prevalence rates of ICHD-II-defined migraine in children; and (4) incidence rates of migraine from prospective longitudinal studies. Methods A comprehensive review of the literature on the prevalence of migraine subtypes and tension-type headache defined by ICHD-II criteria during the past decade was conducted and aggregate weighted rates across studies were derived. Results Across the 19 studies of adults that employed the ICHD-II criteria, the aggregate weighted estimates of the 12-month prevalence of definite migraine are 11.5%, and probable migraine of 7%, yielding a total of 18.5%. The cross-study weighted aggregate rate of migraine with aura is 4.4%, chronic migraine is 0.5%, and of tension-type headache is 13%. There has been even greater growth in international prevalence data on migraine in children, with a total of 21 studies of children that have employed the ICDH-II criteria. The aggregate weighted rate of definite migraine in children is 10.1% and migraine with aura is 1.6%. The well-established demographic correlates of migraine including the equal sex ratio in childhood, with increasing prevalence of migraine in females across adolescence to mid-adulthood were confirmed in these studies. Despite increasing effort to increase awareness of migraine, approximately 50% of those with frequent and/or severe migraine do not receive professional treatment. Conclusions This review demonstrates that the descriptive epidemiology of migraine has reached its maturity. The prevalence rates and sociodemographic correlates have been stable across 50 years. These developments justify a shift in efforts to the application of the designs and methods of analytic epidemiology. Retrospective casecontrol studies followed by prospective cohort studies that test specific associations are likely to enhance our understanding of the predictors of incidence and progression of migraine, subtypes of migraine with differential patterns of onset and course, and specific environmental exposures that may have either causal or provocative influences on migraine etiology.
C1 NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
RP Merikangas, KR (reprint author), NIMH, Genet Epidemiol Res Branch, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA.
FU National Institute of Mental Health [Z01 MH002804]
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health (Z01 MH002804). The views and
opinions expressed in this article are those of the author and should
not be construed to represent the views of any of the sponsoring
organizations, agencies, or U.S. Government. The principal author takes
full responsibility for the data presented in this study, analysis of
the data, conclusions, and conduct of the research. The author had full
access to those data and has maintained the right to publish any and all
data independent of any third party.
NR 126
TC 55
Z9 55
U1 1
U2 23
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0017-8748
EI 1526-4610
J9 HEADACHE
JI Headache
PD FEB
PY 2013
VL 53
IS 2
BP 230
EP 246
DI 10.1111/head.12038
PG 17
WC Clinical Neurology
SC Neurosciences & Neurology
GA 096FN
UT WOS:000315389700002
PM 23432441
ER
PT J
AU Thierry-Chef, I
Dabin, J
Friberg, EG
Hermen, J
Istad, TS
Jahnen, A
Krille, L
Lee, C
Maccia, C
Nordenskjold, A
Olerud, HM
Rani, K
Rehel, JL
Simon, SL
Struelens, L
Kesminiene, A
AF Thierry-Chef, Isabelle
Dabin, Jeremie
Friberg, Eva G.
Hermen, Johannes
Istad, Tore S.
Jahnen, Andreas
Krille, Lucian
Lee, Choonsik
Maccia, Carlo
Nordenskjold, Arvid
Olerud, Hilde M.
Rani, Kaddour
Rehel, Jean-Luc
Simon, Steven L.
Struelens, Lara
Kesminiene, Ausrele
TI Assessing Organ Doses from Paediatric CT Scans-A Novel Approach for an
Epidemiology Study (the EPI-CT Study)
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Article
DE paediatric computed tomography; organ dose reconstruction; scanner
settings; leukaemia; cancer risk
ID MONTE-CARLO-SIMULATION; COMPUTED-TOMOGRAPHY; CANCER-RISKS; RADIATION;
PHANTOMS
AB The increasing worldwide use of paediatric computed tomography (CT) has led to increasing concerns regarding the subsequent effects of exposure to radiation. In response to this concern, the international EPI-CT project was developed to study the risk of cancer in a large multi-country cohort. In radiation epidemiology, accurate estimates of organ-specific doses are essential. In EPI-CT, data collection is split into two time periods-before and after introduction of the Picture Archiving Communication System (PACS) introduced in the 1990s. Prior to PACS, only sparse information about scanner settings is available from radiology departments. Hence, a multi-level approach was developed to retrieve information from a questionnaire, surveys, scientific publications, and expert interviews. For the years after PACS was introduced, scanner settings will be extracted from Digital Imaging and Communications in Medicine (DICOM) headers, a protocol for storing medical imaging data. Radiation fields and X-ray interactions within the body will be simulated using phantoms of various ages and Monte-Carlo-based radiation transport calculations. Individual organ doses will be estimated for each child using an accepted calculation strategy, scanner settings, and the radiation transport calculations. Comprehensive analyses of missing and uncertain dosimetry data will be conducted to provide uncertainty distributions of doses.
C1 [Thierry-Chef, Isabelle; Kesminiene, Ausrele] Int Agcy Res Canc, F-69008 Lyon, France.
[Dabin, Jeremie; Struelens, Lara] CEN SCK, Belgian Nucl Res Ctr, B-2400 Mol, Belgium.
[Friberg, Eva G.; Istad, Tore S.; Olerud, Hilde M.] Norwegian Radiat Protect Author, N-1332 Osteras, Norway.
[Hermen, Johannes; Jahnen, Andreas; Rani, Kaddour] Publ Res Ctr Henri Tudor, L-1855 Luxembourg, Luxembourg.
[Krille, Lucian] Johannes Gutenberg Univ Mainz, Inst Med Biostat Epidemiol & Informat, Univ Med Ctr, D-55131 Mainz, Germany.
[Lee, Choonsik; Simon, Steven L.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA.
[Maccia, Carlo] CAATS 43, F-92340 Bourg La Reine, France.
[Nordenskjold, Arvid] Karolinska Inst, Karolinska Univ Hosp, Clin Epidemiol Unit, Dept Med, SE-171 Stockholm 76, Sweden.
[Olerud, Hilde M.] Univ Oslo, Inst Phys, N-0316 Oslo, Norway.
[Rani, Kaddour] Univ Lorraine, Res Ctr Automat Control, F-54052 Nancy, France.
[Rehel, Jean-Luc] PRP HOM SER UEM, Radiat Protect & Nucl Safety Inst, F-92262 Fontenay Aux Roses, France.
RP Thierry-Chef, I (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69008 Lyon, France.
EM thierrychefi@iarc.fr; jeremie.dabin@SCKCEN.BE; Eva.Friberg@nrpa.no;
johannes.hermen@tudor.lu; Tore.Istad@nrpa.no; andreas.jahnen@tudor.lu;
krille1@imbei.uni-mainz.de; leechoonsik@mail.nih.gov;
carlo-maccia@neuf.fr; arvid.nordenskjold@ki.se; Hilde.Olerud@nrpa.no;
kaddour.rani@tudor.lu; Jean-luc.rehel@irsn.fr; ssimon@mail.nih.gov;
lara.struelens@SCKCEN.BE; kesminienea@iarc.fr
RI Lee, Choonsik/C-9023-2015;
OI Lee, Choonsik/0000-0003-4289-9870; Jahnen, Andreas/0000-0002-7379-5145
FU European Community's Seventh Framework Programme (FP7) [269912-EPI-CT]
FX The study is supported by the European Community's Seventh Framework
Programme (FP7/2007-2013) under grant agreement number 269912-EPI-CT:
Epidemiological study to quantify risks for paediatric computerized
tomography and to optimise doses. The authors aknowledge the members of
the EPI-CT consortium: Tina Veje Andersen, Sarah Baatout, Marie-Odile
Bernier, Elisabeth Cardis, Florent de Vathaire, Maria Gomolka, Janet
Hall, Michael Hauptmann, Christoffer Johansen, Magnus Kaijser, Kristina
Kjaerheim, Dominique Laurier, Astrid Liland, Carita Lindholm, Mark
Pearce, Hubert Thierens.
NR 25
TC 16
Z9 17
U1 0
U2 10
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD FEB
PY 2013
VL 10
IS 2
BP 717
EP 728
DI 10.3390/ijerph10020717
PG 12
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 096ID
UT WOS:000315396500020
PM 23429160
ER
PT J
AU Henry, DB
Dymnicki, AB
Schoeny, ME
Meyer, AL
Martin, NC
AF Henry, David B.
Dymnicki, Allison B.
Schoeny, Michael E.
Meyer, Aleta L.
Martin, Nina C.
CA Multisite Violence Prevention Proj
TI Middle school students overestimate normative support for aggression and
underestimate normative support for nonviolent problem-solving
strategies
SO JOURNAL OF APPLIED SOCIAL PSYCHOLOGY
LA English
DT Article
ID MULTISITE VIOLENCE PREVENTION; PLURALISTIC IGNORANCE; COLLEGE-STUDENTS;
DRINKING NORMS; FEEDBACK; BEHAVIOR; GENDER; PERCEPTIONS; CHILDREN;
PROGRAM
AB This study tested five hypotheses related to the accuracy of students' perceptions of school norms for aggression and nonviolent problem-solving strategies with two cohorts (ns = 852 and 968) of 6th-grade students in 12 schools. Students consistently overestimated peer normative support for aggression and underestimated peer normative support for nonviolent problem-solving strategies. This effect remained significant in tests of moderation by gender, ethnicity, and aggression level. Tests for moderation by the degree of provocation (e. g., if a student was hit first) and a test measuring actual norms from eighth graders and perceived norms from seventh graders suggested that the discrepancy was not due to self-serving bias or social desirability. Longitudinal analysis found that the discrepancy remained through 8th grade. The discrepancy between actual and perceived norms has implications for risk and violence prevention, which are discussed.
C1 [Henry, David B.] Univ Illinois, Chicago, IL 60608 USA.
[Dymnicki, Allison B.] Amer Inst Res, Washington, DC 20007 USA.
[Schoeny, Michael E.] Univ Chicago, Chicago, IL 60637 USA.
[Meyer, Aleta L.] NIDA, Bethesda, MD USA.
[Martin, Nina C.; Multisite Violence Prevention Proj] Vanderbilt Univ, Nashville, TN USA.
RP Henry, DB (reprint author), Univ Illinois, Inst Hlth Res & Policy, 1747 W Roosevelt Rd, Chicago, IL 60608 USA.
EM dhenry@uic.edu
NR 49
TC 4
Z9 4
U1 2
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9029
J9 J APPL SOC PSYCHOL
JI J. Appl. Soc. Psychol.
PD FEB
PY 2013
VL 43
IS 2
BP 433
EP 445
DI 10.1111/j.1559-1816.2013.01027.x
PG 13
WC Psychology, Social
SC Psychology
GA 091DB
UT WOS:000315028100018
ER
PT J
AU Gliozzi, M
Greenwell-Wild, T
Jin, WW
Moutsopoulos, NM
Kapsogeorgou, E
Moutsopoulos, HM
Wahl, SM
AF Gliozzi, Maria
Greenwell-Wild, Teresa
Jin, Wenwen
Moutsopoulos, Niki M.
Kapsogeorgou, Efstathia
Moutsopoulos, Haralampos M.
Wahl, Sharon M.
TI A link between interferon and augmented plasmin generation in exocrine
gland damage in Sjogren's syndrome
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Article
DE tPA; Macrophage; Salivary gland; Cytokine; Plasminogen; MMP
ID LEUKOCYTE PROTEASE INHIBITOR; LABIAL SALIVARY-GLANDS; SQUAMOUS-CELL
CARCINOMA; NECROSIS-FACTOR-ALPHA; CARBOXYPEPTIDASE-M; CATHEPSIN-B;
ANNEXIN-II; 1-MATRIX METALLOPROTEINASE; ACINAR STRUCTURE; HUMAN
MONOCYTES
AB Sjogren's syndrome is an autoimmune disease that targets exocrine glands, but often exhibits systemic manifestations. Infiltration of the salivary and lacrimal glands by lymphoid and myeloid cells orchestrates a perpetuating immune response leading to exocrine gland damage and dysfunction. Th1 and Th17 lymphocyte populations and their products recruit additional lymphocytes, including B cells, but also large numbers of macrophages, which accumulate with disease progression. In addition to cytokines, chemokines, chitinases, and lipid mediators, macrophages contribute to a proteolytic milieu, underlying tissue destruction,, inappropriate repair, and compromised glandular functions. Among the proteases enhanced in this local, environment are matrix metalloproteases (MMP) and plasmin, generated by plasminogen activation, dependent upon plasminogen activators, such as tissue plasminogen activator (tPA). Not previously associated with salivary gland pathology, our evidence implicates enhanced tPA in the context of inflamed salivary glands revolving around lymphocyte-mediated activation of macrophages. Tracking down the mechanism of macrophage plasmin activation, the cytokines IFN gamma and to a lesser extent, IFN alpha, via Janus kinase (JAK) and signal transducer and activator of transcription (STAT) activation, were found to be pivotal for driving the plasmin cascade of proteolytic events culminating in perpetuation of the inflammation and tissue damage, and suggesting intervention strategies to blunt irreversible tissue destruction. Published by Elsevier Ltd.
C1 [Gliozzi, Maria; Greenwell-Wild, Teresa; Jin, Wenwen; Moutsopoulos, Niki M.; Wahl, Sharon M.] NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA.
[Kapsogeorgou, Efstathia; Moutsopoulos, Haralampos M.] Natl Univ Athens, Sch Med, Dept Pathophysiol, Athens 11527, Greece.
RP Wahl, SM (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, Bldg 30,Room 320,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA.
EM smwahl@dir.nidcr.nih.gov
FU Intramural Research Program of the NIH, National Institute of Dental and
Craniofacial Research
FX The authors are grateful to Calley Grace for editorial assistance and
Alfredo Molinolo, NIDCR, NIH for expertise in immunohistochemistry and
scanning. This research was supported in part by the Intramural Research
Program of the NIH, National Institute of Dental and Craniofacial
Research.
NR 69
TC 12
Z9 13
U1 3
U2 9
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
EI 1095-9157
J9 J AUTOIMMUN
JI J. Autoimmun.
PD FEB
PY 2013
VL 40
BP 122
EP 133
DI 10.1016/j.jaut.2012.09.003
PG 12
WC Immunology
SC Immunology
GA 095XJ
UT WOS:000315368000012
PM 23110742
ER
PT J
AU Geller, J
He, Z
Perl, Y
Morrey, CP
Xu, J
AF Geller, James
He, Zhe
Perl, Yehoshua
Morrey, C. Paul
Xu, Julia
TI Rule-based support system for multiple UMLS semantic type assignments
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE UMLS; Semantic Network; Metathesaurus; UMLS editing; Semantic type
definitions; Concept Insertion
ID MEDICAL LANGUAGE SYSTEM; OBJECT-ORIENTED DATABASE; REPRESENTATION;
ABSTRACTION; TERMINOLOGY; NETWORK
AB Background: When new concepts are inserted into the UMLS, they are assigned one or several semantic types from the UMLS Semantic Network by the UMLS editors. However, not every combination of semantic types is permissible. It was observed that many concepts with rare combinations of semantic types have erroneous semantic type assignments or prohibited combinations of semantic types. The correction of such errors is resource-intensive.
Objective: We design a computational system to inform UMLS editors as to whether a specific combination of two, three, four, or five semantic types is permissible or prohibited or questionable.
Methods: We identify a set of inclusion and exclusion instructions in the UMLS Semantic Network documentation and derive corresponding rule-categories as well as rule-categories from the UMLS concept content. We then design an algorithm adviseEditor based on these rule-categories. The algorithm specifies rules for an editor how to proceed when considering a tuple (pair, triple, quadruple, quintuple) of semantic types to be assigned to a concept.
Results: Eight rule-categories were identified. A Web-based system was developed to implement the adviseEditor algorithm, which returns for an input combination of semantic types whether it is permitted, prohibited or (in a few cases) requires more research. The numbers of semantic type pairs assigned to each rule-category are reported. Interesting examples for each rule-category are illustrated. Cases of semantic type assignments that contradict rules are listed, including recently introduced ones.
Conclusion: The adviseEditor system implements explicit and implicit knowledge available in the UMLS in a system that informs UMLS editors about the permissibility of a desired combination of semantic types. Using adviseEditor might help accelerate the work of the UMLS editors and prevent erroneous semantic type assignments. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Geller, James; He, Zhe; Perl, Yehoshua] New Jersey Inst Technol, Newark, NJ 07102 USA.
[Morrey, C. Paul] Utah Valley Univ, Orem, UT USA.
[Xu, Julia] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP He, Z (reprint author), New Jersey Inst Technol, Dept Comp Sci, Newark, NJ 07102 USA.
EM zh5@njit.edu
RI He, Zhe/J-2336-2014; He, Zhe/E-1549-2017
OI He, Zhe/0000-0003-3608-0244; He, Zhe/0000-0003-3608-0244
FU NLM [R-01-LM008445-01A2]
FX This work was partially supported by the NLM under Grant
R-01-LM008445-01A2. We wish to thank O. Bodenreider for suggesting the
need for an implementation of our Refined Semantic Network in the form
of a computer system to support UMLS editors when performing new UMLS
semantic type assignments.
NR 25
TC 2
Z9 2
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD FEB
PY 2013
VL 46
IS 1
BP 97
EP 110
DI 10.1016/j.jbi.2012.09.007
PG 14
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 095VE
UT WOS:000315362300011
PM 23041716
ER
PT J
AU Foster, BL
Nagatomo, KJ
Tso, HW
Tran, AB
Nociti, FH
Narisawa, S
Yadav, MC
McKee, MD
Millan, JL
Somerman, MJ
AF Foster, B. L.
Nagatomo, K. J.
Tso, H. W.
Tran, A. B.
Nociti, F. H., Jr.
Narisawa, S.
Yadav, M. C.
McKee, M. D.
Millan, J. L.
Somerman, M. J.
TI Tooth Root Dentin Mineralization Defects in a Mouse Model of
Hypophosphatasia
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE TISSUE-NONSPECIFIC ALKALINE PHOSPHATASE (TNAP); DENTIN; PYROPHOSPHATE;
OSTEOPONTIN; MATRIX VESICLES
ID ALKALINE-PHOSPHATASE ACTIVITY; EXTRACELLULAR-MATRIX PROTEINS;
ENZYME-REPLACEMENT THERAPY; EXTRINSIC FIBER CEMENTUM; HYDROXYAPATITE
FORMATION; APPOSITIONAL MINERALIZATION; INFANTILE HYPOPHOSPHATASIA;
SKELETAL MINERALIZATION; PERIODONTAL-LIGAMENT; CIRCUMPULPAL DENTIN
AB Tissue-nonspecific alkaline phosphatase (TNAP) is expressed in mineralizing tissues and functions to reduce pyrophosphate (PPi), a potent inhibitor of mineralization. Loss of TNAP function causes hypophosphatasia (HPP), a heritable disorder marked by increased PPi, resulting in rickets and osteomalacia. Tooth root cementum defects are well described in both HPP patients and in Alpl(-/-) mice, a model for infantile HPP. In Alpl(-/-) mice, dentin mineralization is specifically delayed in the root; however, reports from human HPP patients are variable and inconsistent regarding dentin defects. In the current study, we aimed to define the molecular basis for changes in dentinogenesis observed in Alpl(-/-) mice. TNAP was found to be highly expressed by mature odontoblasts, and Alpl(-/-) molar and incisor roots featured defective dentin mineralization, ranging from a mild delay to severely disturbed root dentinogenesis. Lack of mantle dentin mineralization was associated with disordered and dysmorphic odontoblasts having disrupted expression of marker genes osteocalcin and dentin sialophosphoprotein. The formation of, initiation of mineralization within, and rupture of matrix vesicles in Alpl(-/-) dentin matrix was not affected. Osteopontin (OPN), an inhibitor of mineralization that contributes to the skeletal pathology in Alpl(-/-) mice, was present in the generally unmineralized Alpl(-/-) mantle dentin at ruptured mineralizing matrix vesicles, as detected by immunohistochemistry and by immunogold labeling. However, ablating the OPN-encoding Spp1 gene in Alpl(-/-) mice was insufficient to rescue the dentin mineralization defect. Administration of bioengineered mineral-targeting human TNAP (ENB-0040) to Alpl(-/-) mice corrected defective dentin mineralization in the molar roots. These studies reveal that TNAP participates in root dentin formation and confirm that reduction of PPi during dentinogenesis is necessary for odontoblast differentiation, dentin matrix secretion, and mineralization. Furthermore, these results elucidate developmental mechanisms underlying dentin pathology in HPP patients, and begin to explain the reported variability in the dentin/pulp complex pathology in these patients. (C) 2013 American Society for Bone and Mineral Research.
C1 [Foster, B. L.; Tran, A. B.; Nociti, F. H., Jr.; Somerman, M. J.] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bethesda, MD 20892 USA.
[Nagatomo, K. J.; Tso, H. W.] Univ Washington, Sch Dent, Dept Periodont, Seattle, WA 98195 USA.
[Narisawa, S.; Yadav, M. C.; Millan, J. L.] Sanford Burnham Med Res Inst, Sanford Childrens Hlth Res Ctr, La Jolla, CA USA.
[McKee, M. D.] McGill Univ, Fac Dent, Montreal, PQ, Canada.
[McKee, M. D.] McGill Univ, Dept Anat & Cell Biol, Fac Med, Montreal, PQ, Canada.
RP Foster, BL (reprint author), Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bldg 50,Room 4120, Bethesda, MD 20892 USA.
EM brian.foster@nih.gov
RI Nociti, Francisco/G-4907-2015; Foster, Brian/H-8375-2015
OI Foster, Brian/0000-0003-3444-0576
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) of the National Institutes of Health (NIH) [NIH R01DE15109, NIH
R01 AR47908, R01 DE12889, CIHR MOP-97858]
FX This research was supported in part by the Intramural Research Program
of the National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS) of the National Institutes of Health (NIH). A portion
of this research was completed when BLF, FHN, ABT, and MJS were
affiliated with the University of Washington School of Dentistry,
Department of Periodontics (Seattle, WA, USA). The authors thank Jirawan
Wade for preparing histological sections, Lydia Malynowsky for her help
with immunogold labeling and electron microscopy, Daisy Matsa Dunn for
in situ hybridization, and Tracy Popowics for critical reading of the
manuscript. Grant funding: NIH R01DE15109 (MJS), NIH R01 AR47908 and R01
DE12889 (JLM), and CIHR MOP-97858 (MDM).
NR 50
TC 33
Z9 35
U1 1
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2013
VL 28
IS 2
BP 271
EP 282
DI 10.1002/jbmr.1767
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 092FT
UT WOS:000315105600006
PM 22991301
ER
PT J
AU Imoto, K
Nadem, C
Moriwaki, SI
Nishigori, C
Oh, KS
Khan, SG
Goldstein, AM
Kraemer, KH
AF Imoto, Kyoko
Nadem, Carine
Moriwaki, Shin-Ichi
Nishigori, Chikako
Oh, Kyu-Seon
Khan, Sikandar G.
Goldstein, Alisa M.
Kraemer, Kenneth H.
TI Ancient origin of a Japanese xeroderma pigmentosum founder mutation
SO JOURNAL OF DERMATOLOGICAL SCIENCE
LA English
DT Letter
ID DNA-REPAIR DEFICIENCY; GROUP-A; DISEASE
C1 [Imoto, Kyoko; Nadem, Carine; Oh, Kyu-Seon; Khan, Sikandar G.; Kraemer, Kenneth H.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Imoto, Kyoko] Nara Med Univ, Dept Dermatol, Nara, Japan.
[Moriwaki, Shin-Ichi] Osaka Med Coll, Dept Dermatol, Osaka, Japan.
[Nishigori, Chikako] Kobe Univ, Grad Sch Med, Div Dermatol, Kobe, Hyogo 657, Japan.
[Goldstein, Alisa M.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Kraemer, KH (reprint author), NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res, Bldg 37 Room 4002 MSC 4258, Bethesda, MD 20892 USA.
EM kraemerk@nih.gov
FU Intramural NIH HHS [ZIA BC004517-36]
NR 10
TC 2
Z9 3
U1 0
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0923-1811
EI 1873-569X
J9 J DERMATOL SCI
JI J. Dermatol. Sci.
PD FEB
PY 2013
VL 69
IS 2
BP 175
EP 176
DI 10.1016/j.jdermsci.2012.10.008
PG 2
WC Dermatology
SC Dermatology
GA 098HD
UT WOS:000315538800012
PM 23194742
ER
PT J
AU Fleming, JM
Ginsburg, E
McAndrew, CW
Heger, CD
Cheston, L
Rodriguez-Canales, J
Vonderhaar, BK
Goldsmith, P
AF Fleming, J. M.
Ginsburg, E.
McAndrew, C. W.
Heger, C. D.
Cheston, L.
Rodriguez-Canales, J.
Vonderhaar, B. K.
Goldsmith, P.
TI Characterization of Delta 7/11, a functional prolactin-binding protein
SO JOURNAL OF MOLECULAR ENDOCRINOLOGY
LA English
DT Article
DE prolactin; prolactin receptor; mammary; alternative splicing;
prolactin-binding protein
ID MAMMARY-GLAND DEVELOPMENT; FACTOR 16K HPRL; BREAST-CANCER;
N-GLYCOSYLATION; RECEPTOR GENE; TUMOR-GROWTH; CELL-LINES; EXPRESSION;
MULTIPLE; ACTIVATION
AB Prolactin is essential for normal mammary gland development and differentiation, and has been shown to promote tumor cell proliferation and chemotherapeutic resistance. Soluble isoforms of the prolactin receptor (PrlR) have been reported to regulate prolactin bioavailability by functioning as 'prolactin-binding proteins'. Included in this category is Delta 7/11, a product of alternate splicing of the PrlR primary transcript. However, the direct interactions of prolactin with Delta 7/11, and the resulting effect on cell behavior, have not been investigated. Herein, we demonstrate the ability of Delta 7/11 to bind prolactin using a novel proximity ligation assay and traditional immunoprecipitation techniques. Biochemical analyses demonstrated that Delta 7/11 was heavily glycosylated, similar to the extracellular domain of the primary PrlR, and that glycosylation regulated the cellular localization and secretion of Delta 7/11. Low levels of Delta 7/11 were detected in serum samples of healthy volunteers, but were undetectable in human milk samples. Expression of Delta 7/11 was also detected in six of the 62 primary breast tumor biopsies analyzed; however, no correlation was found with Delta 7/11 expression and tumor histotype or other patient demographics. Functional analysis demonstrated the ability of Delta 7/11 to inhibit prolactin-induced cell proliferation as well as alter prolactin-induced rescue of cell cycle arrest/early senescence events in breast epithelial cells. Collectively, these data demonstrate that Delta 7/11 is a novel regulatory mechanism of prolactin bioavailability and signaling.
C1 [Fleming, J. M.; Ginsburg, E.; Vonderhaar, B. K.] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA.
[McAndrew, C. W.; Heger, C. D.; Goldsmith, P.] NCI, Antibody Prod & Purificat Unit, NIH, Bethesda, MD 20892 USA.
[Fleming, J. M.; Cheston, L.] N Carolina Cent Univ, Dept Biol, Coll Sci & Technol, Durham, NC 27707 USA.
[Rodriguez-Canales, J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Fleming, JM (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA.
EM jodie.fleming@nccu.edu
FU Center for Cancer Research; Intramural Research Program of the National
Cancer Institute; NCCU-BBRI-Lineberger Partnership in Cancer Research
[U54 CA156735]
FX This research was supported by the Center for Cancer Research, an
Intramural Research Program of the National Cancer Institute, and by the
NCCU-BBRI-Lineberger Partnership in Cancer Research U54 CA156735.
NR 39
TC 3
Z9 3
U1 0
U2 3
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0952-5041
J9 J MOL ENDOCRINOL
JI J. Mol. Endocrinol.
PD FEB
PY 2013
VL 50
IS 1
BP 79
EP 90
DI 10.1530/JME-12-0201
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 098ST
UT WOS:000315569900009
PM 23048206
ER
PT J
AU Bai, Y
Bandara, G
Chan, EC
Maric, I
Simakova, O
Bandara, SN
Lu, WP
Wise, SC
Flynn, DL
Metcalfe, DD
Gilfillan, AM
Wilson, TM
AF Bai, Y.
Bandara, G.
Chan, E. Ching
Maric, I.
Simakova, O.
Bandara, S. N.
Lu, W-P
Wise, S. C.
Flynn, D. L.
Metcalfe, D. D.
Gilfillan, A. M.
Wilson, T. M.
TI Targeting the KIT activating switch control pocket: a novel mechanism to
inhibit neoplastic mast cell proliferation and mast cell activation
SO LEUKEMIA
LA English
DT Article
DE mastocytosis; switch pocket; KIT; KIT D816V; tyrosine kinase inhibitor;
mast cell
ID TYROSINE KINASE INHIBITORS; SYSTEMIC MASTOCYTOSIS; C-KIT; DEPENDENT
ACTIVATION; STI-571 INHIBITION; RI; MUTATIONS; PKC412; GROWTH; DASATINIB
AB Activating mutations in the receptor tyrosine kinase KIT, most notably KIT D816V, are commonly observed in patients with systemic mastocytosis. Thus, inhibition of KIT has been a major focus for treatment of this disorder. Here we investigated a novel approach to such inhibition. Utilizing rational drug design, we targeted the switch pocket (SP) of KIT, which regulates its catalytic conformation. Two SP inhibitors thus identified, DP-2976 and DP-4851, were examined for effects on neoplastic mast cell proliferation and mast cell activation. Autophosphorylation of both wild-type and, where also examined, KIT D816V activation was blocked by these compounds in transfected 293T cells, HMC 1.1 and 1.2 human mast cell lines, and in CD34(+)-derived human mast cells activated by stem cell factor (SCF). Both inhibitors induced apoptosis in the neoplastic mast cell lines and reduced survival of primary bone marrow mast cells from patients with mastocytosis. Moreover, the SP inhibitors more selectively blocked SCF potentiation of Fc epsilon RI-mediated degranulation. Overall, SP inhibitors represent an innovative mechanism of KIT inhibition whose dual suppression of KIT D816V neoplastic mast cell proliferation and SCF-enhanced mast cell activation may provide significant therapeutic benefits. Leukemia (2013) 27, 278-285; doi:10.1038/leu.2012.218
C1 [Bai, Y.; Bandara, G.; Chan, E. Ching; Bandara, S. N.; Metcalfe, D. D.; Gilfillan, A. M.; Wilson, T. M.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Maric, I.; Simakova, O.] Ctr Clin, Dept Lab Med, Bethesda, MD USA.
[Lu, W-P; Wise, S. C.; Flynn, D. L.] Deciphera Pharmaceut, Lawrence, KS USA.
RP Wilson, TM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 12S235A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM twilson@niaid.nih.gov
FU Division of Intramural Research of the NIAID, NIH
FX We thank Dr Cem Akin (Brigham and Women's Hospital) for technical advice
with the ex vivo studies and Sarka Smrzova (LAD) for technical support
with HuMC cultures. We thank all the subjects as well as the LAD
clinical research staff for their contributions. This study was
supported in part by the Division of Intramural Research of the NIAID,
NIH. Deciphera Pharmaceuticals supplied the study compounds and
performed the in vitro kinase assays.
NR 33
TC 13
Z9 13
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD FEB
PY 2013
VL 27
IS 2
BP 278
EP 285
DI 10.1038/leu.2012.218
PG 8
WC Oncology; Hematology
SC Oncology; Hematology
GA 098MO
UT WOS:000315553600004
PM 22907049
ER
PT J
AU Bhambhani, V
Introne, WJ
Lungu, C
Cullinane, A
Toro, C
AF Bhambhani, Vikas
Introne, Wendy J.
Lungu, Codrin
Cullinane, Andrew
Toro, Camilo
TI Chediak-Higashi syndrome presenting as young-onset levodopa-responsive
parkinsonism
SO MOVEMENT DISORDERS
LA English
DT Article
ID PHENOTYPE; GENOTYPE
C1 [Bhambhani, Vikas; Cullinane, Andrew] NHGRI, Human Biochem Genet Sect, Bethesda, MD 20892 USA.
[Introne, Wendy J.; Toro, Camilo] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Lungu, Codrin] Natl Inst Neurol Disorders & Stroke, Off Clin Director, NIH, Bethesda, MD USA.
RP Toro, C (reprint author), NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
EM toroc@mail.nih.gov
FU National Human Genome Research Institute Intramural Research Program
FX This work was conducted through funding from the National Human Genome
Research Institute Intramural Research Program.
NR 9
TC 9
Z9 9
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD FEB
PY 2013
VL 28
IS 2
BP 127
EP 129
DI 10.1002/mds.25386
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 096JF
UT WOS:000315399300004
PM 23436631
ER
PT J
AU Lynch, DR
Pandolfo, M
Schulz, JB
Perlman, S
Delatycki, MB
Payne, RM
Shaddy, R
Fischbeck, KH
Farmer, J
Kantor, P
Raman, SV
Hunegs, L
Odenkirchen, J
Miller, K
Kaufmann, P
AF Lynch, David R.
Pandolfo, Massimo
Schulz, Jorg B.
Perlman, Susan
Delatycki, Martin B.
Payne, R. Mark
Shaddy, Robert
Fischbeck, Kenneth H.
Farmer, Jennifer
Kantor, Paul
Raman, Subha V.
Hunegs, Lisa
Odenkirchen, Joanne
Miller, Kristy
Kaufmann, Petra
TI Common data elements for clinical research in Friedreich's ataxia
SO MOVEMENT DISORDERS
LA English
DT Article
DE cerebellum; dorsal root ganglion; mitochondrion; clinical measure; NINDS
Common Data Elements
ID QUALITY-OF-LIFE; BRAIN-INJURY RECOMMENDATIONS; PLACEBO-CONTROLLED TRIAL;
HIGH-DOSE IDEBENONE; PERFORMANCE-MEASURES; WORKING GROUP; DEMOGRAPHICS;
DEFICIENCY; FEATURES; FRATAXIN
AB To reduce study start-up time, increase data sharing, and assist investigators conducting clinical studies, the National Institute of Neurological Disorders and Stroke embarked on an initiative to create common data elements for neuroscience clinical research. The Common Data Element Team developed general common data elements, which are commonly collected in clinical studies regardless of therapeutic area, such as demographics. In the present project, we applied such approaches to data collection in Friedreich's ataxia (FRDA), a neurological disorder that involves multiple organ systems. To develop FRDA common data elements, FRDA experts formed a working group and subgroups to define elements in the following: ataxia and performance measures; biomarkers; cardiac and other clinical outcomes; and demographics, laboratory tests, and medical history. The basic development process included identification of international experts in FRDA clinical research, meeting by teleconference to develop a draft of standardized common data elements recommendations, vetting of recommendations across the subgroups, and dissemination of recommendations to the research community for public comment. The full recommendations were published online in September 2011 at http://www.commondataelements.ninds.nih.gov/FA.aspx. The subgroups recommendations are classified as core, supplemental, or exploratory. Template case report forms were created for many of the core tests. The present set of data elements should ideally lead to decreased initiation time for clinical research studies and greater ability to compare and analyze data across studies. Their incorporation into new, ongoing studies will be assessed in an ongoing fashion to define their utility in FRDA. (c) 2012 Movement Disorder Society
C1 [Lynch, David R.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[Lynch, David R.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA.
[Lynch, David R.; Shaddy, Robert] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Pandolfo, Massimo] Univ Libre Brussels, Brussels, Belgium.
[Schulz, Jorg B.] Rhein Westfal TH Aachen, Univ Hosp, Dept Neurol, Aachen, Germany.
[Schulz, Jorg B.] Rhein Westfal TH Aachen, Univ Hosp, JARA Brain, Aachen, Germany.
[Perlman, Susan] Univ Calif Los Angeles, Los Angeles, CA USA.
[Delatycki, Martin B.] Murdoch Childrens Res Inst, Melbourne, Vic, Australia.
[Payne, R. Mark] Indiana Univ, Indianapolis, IN 46204 USA.
[Shaddy, Robert] Univ Penn, Dept Pediat, Div Cardiol, Philadelphia, PA 19104 USA.
[Fischbeck, Kenneth H.; Odenkirchen, Joanne; Kaufmann, Petra] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Farmer, Jennifer] Friedreichs Ataxia Res Alliance, Downingtown, PA USA.
[Kantor, Paul] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Raman, Subha V.] Ohio State Univ, Columbus, OH 43210 USA.
[Hunegs, Lisa; Miller, Kristy] KAI Res Inc, Rockville, MD USA.
RP Lynch, DR (reprint author), Childrens Hosp Philadelphia, Abramson Res Ctr, Div Neurol, Room 502,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM lynchd@mail.med.upenn.edu
RI Schulz, Jorg/D-9786-2012
OI Schulz, Jorg/0000-0002-8903-0593
FU National Institute of Neurological Disorders and Stroke; National
Institutes of Health [N01-NS-7-2372]; Friedreich ataxia Research
alliance for the CCRNFA; European Union Framework Programme 7 for EFACTS
FX The Common Data Element Project is funded by the National Institute of
Neurological Disorders and Stroke, National Institutes of Health
(contract no.: N01-NS-7-2372). Additional support was received from the
Friedreich ataxia Research alliance for the CCRNFA, and from the
European Union Framework Programme 7 for EFACTS. Drs. Lynch and Pandolfo
contributed equally to the present work.
NR 34
TC 9
Z9 9
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD FEB
PY 2013
VL 28
IS 2
BP 190
EP 195
DI 10.1002/mds.25201
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 096JF
UT WOS:000315399300013
PM 23239403
ER
PT J
AU Rutkowski, A
Bonnemann, C
Brown, S
Thorsteinsdottir, S
Dominov, J
Ruegg, MA
Matter, ML
Guttridge, D
Crosbie-Watson, RH
Kardon, G
Nagaraju, K
Girgenrath, M
Burkin, DJ
AF Rutkowski, Anne
Boennemann, Carsten
Brown, Susan
Thorsteinsdottir, Solveig
Dominov, Janice
Ruegg, Markus A.
Matter, Michelle L.
Guttridge, Denis
Crosbie-Watson, Rachelle H.
Kardon, Gabrielle
Nagaraju, Kanneboyina
Girgenrath, Mahasweta
Burkin, Dean J.
TI Report on the Myomatrix Conference April 22-24, 2012, University of
Nevada, Reno, Nevada, USA
SO NEUROMUSCULAR DISORDERS
LA English
DT Article
DE Conference report; Congenital muscular dystrophy; Translational Research
Road Map; MDC1A; DMD; Dystroglycanopathy; Collagen VI related myopathy;
Muscular dystrophy; Extracellular matrix; Fibrosis; Laminin; Integrin
AB The Myomatrix 2012 conference held April 22-24th, 2012 at the University of Nevada, Reno convened 73 international participants to discuss the dynamic relationship between muscle and its matrix in muscular dystrophy with a specific focus on congenital muscular dystrophy. Seven sessions over 2 1/2 days defined three central themes: (1) the role of extracellular matrix proteins and compartments in development and specifically in congenital muscular dystrophy (CMD) (2) the role of extracellular matrix signaling and adhesion to membrane receptors and (3) the balance and interplay between inflammation and fibrosis as drivers of altered matrix stiffness, impaired regeneration and progressive dystrophy. This report highlights major conference findings and the translational roadmap as defined by conference attendees. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Rutkowski, Anne] Cure CMD, Kaiser SCPMG, Olathe, KS 66051 USA.
[Boennemann, Carsten] NINDS, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
[Boennemann, Carsten] NINDS, Neurogenet Disorders Childhood Sect, Bethesda, MD 20892 USA.
[Brown, Susan] Univ London, Royal Vet Coll, Dept Vet Basic Sci, London NW1 0TU, England.
[Thorsteinsdottir, Solveig] Univ Lisbon, Dept Biol Anim, Ctr Biol Ambiental, P-1699 Lisbon, Portugal.
[Dominov, Janice] Boston Biomed Res Inst, Watertown, MA 02472 USA.
[Ruegg, Markus A.] Univ Basel, Biozentrum, CH-4003 Basel, Switzerland.
[Matter, Michelle L.] Univ Hawaii Manoa, Honolulu, HI 96822 USA.
[Guttridge, Denis] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA.
[Crosbie-Watson, Rachelle H.] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90095 USA.
[Kardon, Gabrielle] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA.
[Nagaraju, Kanneboyina] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA.
[Girgenrath, Mahasweta] Boston Univ, Coll Hlth & Rehabil Sci, Boston, MA 02215 USA.
[Burkin, Dean J.] Univ Nevada, Sch Med, Dept Pharmacol, Ctr Mol Med, Reno, NV 89557 USA.
RP Burkin, DJ (reprint author), Univ Nevada, Sch Med, Dept Pharmacol, Ctr Mol Med, Reno, NV 89557 USA.
EM dburkin@medicine.nevada.edu
RI Thorsteinsdottir, Solveig/M-3561-2013;
OI Thorsteinsdottir, Solveig/0000-0002-9018-3431; Brown,
Sue/0000-0001-8112-933X
FU NIH/NIAMS [R13AR062995]; Muscular Dystrophy Association [MDA219240];
Genzyme Sanofi; AVIBioPharma; Cellular Dynamics; Cure Congenital
Muscular Dystrophy (Cure CMD); LGMD2I Fund; PTC Therapeutics; Santhera
Pharmaceuticals; Ultragenyx
FX This conference was supported by NIH/NIAMS (R13AR062995) and Muscular
Dystrophy Association (MDA219240). Sponsorship for the conference was
provided by Genzyme Sanofi, AVIBioPharma, Cellular Dynamics, Cure
Congenital Muscular Dystrophy (Cure CMD), LGMD2I Fund, PTC Therapeutics,
Santhera Pharmaceuticals and Ultragenyx. The conference organizers wish
to thank the University of Nevada, Reno for hosting the Myomatrix
conference within the Center for Molecular Medicine and all conference
participants. To view the Myomatrix conference program and abstracts:
www.curecmd.org/myomatrix.
NR 0
TC 3
Z9 3
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD FEB
PY 2013
VL 23
IS 2
BP 188
EP 191
DI 10.1016/j.nmd.2012.06.353
PG 4
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 098IO
UT WOS:000315542900015
PM 22800409
ER
PT J
AU Leggio, L
Zywiak, WH
McGeary, JE
Edwards, S
Fricchione, SR
Shoaff, JR
Addolorato, G
Swift, RM
Kenna, GA
AF Leggio, Lorenzo
Zywiak, William H.
McGeary, John E.
Edwards, Steven
Fricchione, Samuel R.
Shoaff, Jessica R.
Addolorato, Giovanni
Swift, Robert M.
Kenna, George A.
TI A human laboratory pilot study with baclofen in alcoholic individuals
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article
DE Baclofen; Alcoholism; Cue-reactivity; Alcohol self-administration;
Biobehavioral mechanisms; Genetic polymorphisms
ID PLACEBO-CONTROLLED TRIAL; DRD4 VNTR POLYMORPHISM; DEPENDENT PATIENTS;
DOUBLE-BLIND; SEROTONIN TRANSPORTER; GABA(B) RECEPTOR; CUE REACTIVITY;
VALIDATION; SEEKING; SAFETY
AB Preclinical and clinical studies show that the GABA(B) receptor agonist baclofen may represent a pharmacotherapy for alcohol dependence (AD). However, the mechanisms by which baclofen affects drinking are not well characterized; thus this pilot study investigated possible baclofen's biobehavioral mechanisms. The design was a double-blind controlled randomized human laboratory pilot study. Fourteen non-treatment seeking alcohol-dependent heavy drinking subjects received either baclofen 10 mg t.i.d. or an active placebo (cyproheptadine 2 mg t.i.d., to control for sedation) for a 7-day period. At day 8, participants performed an alcohol cue-reactivity (CR) followed by an alcohol self-administration (ASA). Additionally, we explored possible moderators that might guide future larger studies, i.e. anxiety, family history and onset of alcoholism, and D4 dopamine receptor (DRD4) and 5-HTTLPR polymorphisms. The main results were a significant effect of baclofen for increasing stimulation (p=.001) and sedation (p<.01). Furthermore, when drinking during the ASA and the 2 days before was analyzed as a composite variable, there was a significant effect of baclofen to reduce alcohol consumption (p<.01). As for the exploratory analyses, baclofen's effects to increase alcohol sedation and to reduce alcohol consumption were limited to those individuals with DRD >= 7 repeats (DRD4L). Yet, baclofen's effects on alcohol consumption were also moderated by 5-HTTLPR LL genotype. In conclusion, baclofen's ability to reduce alcohol drinking may be related to its effects on the biphasic effects of alcohol, but larger studies are needed to confirm these preliminary findings. Published by Elsevier Inc.
C1 [Leggio, Lorenzo; Zywiak, William H.; McGeary, John E.; Edwards, Steven; Fricchione, Samuel R.; Shoaff, Jessica R.; Swift, Robert M.; Kenna, George A.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA.
[Zywiak, William H.] PIRE, Decis Sci Inst, Pawtucket, RI USA.
[McGeary, John E.; Swift, Robert M.] Vet Affairs Med Ctr, Providence, RI USA.
[Addolorato, Giovanni] Univ Cattolica Sacro Cuore, Inst Internal Med, Rome, Italy.
RP Leggio, L (reprint author), NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, 10 Ctr Dr 10CRC-15330 MSC 1108,Room 1-5429, Bethesda, MD 20892 USA.
EM lorenzo.leggio@nih.gov
RI Leggio, Lorenzo/M-2972-2016;
OI Addolorato, Giovanni/0000-0002-1522-9946
FU Brown University Center for Alcohol and Addiction Studies
FX This study was supported by a Research Excellence Award (REA) grant from
the Brown University Center for Alcohol and Addiction Studies to the PI
(Dr. Leggio).
NR 50
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Z9 20
U1 5
U2 20
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0091-3057
J9 PHARMACOL BIOCHEM BE
JI Pharmacol. Biochem. Behav.
PD FEB
PY 2013
VL 103
IS 4
BP 784
EP 791
DI 10.1016/j.pbb.2012.11.013
PG 8
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 099XX
UT WOS:000315660300013
PM 23262301
ER
PT J
AU Wright, DB
Trian, T
Siddiqui, S
Pascoe, CD
Johnson, JR
Dekkers, BGJ
Dakshinamurti, S
Bagchi, R
Burgess, JK
Kanabar, V
Ojo, OO
AF Wright, David B.
Trian, Thomas
Siddiqui, Sana
Pascoe, Chris D.
Johnson, Jill R.
Dekkers, Bart G. J.
Dakshinamurti, Shyamala
Bagchi, Rushita
Burgess, Janette K.
Kanabar, Varsha
Ojo, Oluwaseun O.
TI Phenotype modulation of airway smooth muscle in asthma
SO PULMONARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
DE Airway smooth muscle; Asthma; Phenotypic plasticity; Contractile
response; Synthetic response
ID EXTRACELLULAR-MATRIX PROTEINS; CCAAT/ENHANCER-BINDING-PROTEIN;
ADENOVIRAL GENE-TRANSFER; SIGNAL-REGULATED KINASE; SERUM RESPONSE
FACTOR; CELL-PROLIFERATION; ALLERGIC-ASTHMA; C/EBP-ALPHA; IN-VITRO;
EXPRESSION
AB The biological responses of airway smooth muscle (ASM) are diverse, in part due to ASM phenotype plasticity. ASM phenotype plasticity refers to the ability of ASM cells to change the degree of a variety of functions, including contractility, proliferation, migration and secretion of inflammatory mediators. This plasticity occurs due to intrinsic or acquired abnormalities in ASM cells, and these abnormalities or predisposition of the ASM cell may alter the ASM response and in some cases recapitulate disease hallmarks of asthma.
These phenotypic changes are ultimately determined by multiple stimuli and occur due to alterations in the intricate balance or reversible state that maintains ASM cells in either a contractile or synthetic state, through processes termed maturation or modulation, respectively. To elucidate the role of ASM phenotype in disease states, numerous in vitro studies have suggested a phenotypic switch in ASM primary cell cultures as an explanation for the plethora of responses mediated by ASM cells. Moreover, there is overwhelming evidence suggesting that the immunomodulatory response of ASM is due to the acquisition of a synthetic phenotype; however, whether this degree of plasticity is present in vivo as opposed to cell culture-based models remains speculative. Nonetheless, this review will give an overall scope of ASM phenotypic markers, triggers of ASM phenotype modulation and novel therapeutic approaches to control ASM phenotype plasticity. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Wright, David B.] Kings Coll London, MRC, London WC2R 2LS, England.
[Wright, David B.] Kings Coll London, Asthma UK Ctr Allerg Mech Asthma, London WC2R 2LS, England.
[Trian, Thomas] Univ Bordeaux 2, Ctr Rech Cardiothorac Bordeaux, INSERM, U1045,Equipe Remodelage Bronch, F-33076 Bordeaux, France.
[Siddiqui, Sana] McGill Univ, Meakins Christie Labs, Dept Med, Montreal, PQ, Canada.
[Siddiqui, Sana] NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA.
[Pascoe, Chris D.] Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada.
[Johnson, Jill R.] Univ London Imperial Coll Sci Technol & Med, Leukocyte Biol Sect, Natl Heart & Lung Inst, London, England.
[Dekkers, Bart G. J.] Univ Groningen, Dept Mol Pharmacol, Groningen Res Inst Asthma, Groningen, Netherlands.
[Dekkers, Bart G. J.] Univ Groningen, COPD, Groningen, Netherlands.
[Dakshinamurti, Shyamala] Univ Manitoba, Sect Neonatol, Womens Hosp WS012, Winnipeg, MB R3E 3P4, Canada.
[Bagchi, Rushita] Univ Manitoba, Dept Physiol, Inst Cardiovasc Sci, St Boniface Hosp Res Ctr, Winnipeg, MB R3E 3P4, Canada.
[Burgess, Janette K.] Univ Sydney, Cell Biol Grp, Woolcock Inst Med Res, Sydney, NSW 2006, Australia.
[Burgess, Janette K.] Univ Sydney, Discipline Pharmacol, Sydney, NSW 2006, Australia.
[Kanabar, Varsha] Kings Coll London, Sackler Inst Pulm Pharmacol, London WC2R 2LS, England.
[Ojo, Oluwaseun O.] Univ Manitoba, Dept Resp Physiol, Biol Breathing Grp, Manitoba Inst Child Hlth, Winnipeg, MB R3E 3P4, Canada.
RP Ojo, OO (reprint author), Univ Manitoba, Dept Resp Physiol, Biol Breathing Grp, Manitoba Inst Child Hlth,John Buhler Res Ctr, Room 641,715 McDermott Ave, Winnipeg, MB R3E 3P4, Canada.
EM ojoo3@cc.umanitoba.ca
RI Burgess, Janette/A-3597-2010;
OI Wright, David/0000-0003-1285-4655; Bagchi, Rushita/0000-0002-9075-0766
FU Alexander McFee Studentship, Faculty of Medicine, McGill University,
Montreal, QC; Imperial College London; National Health & Medical
Research Council, Australia Career Development Fellowship [1032695];
MHRC/SBRC Coordinated Graduate Studentship by the Manitoba Health
Research Council, Canada
FX Sana Siddiqui is the recipient of the Alexander McFee Studentship,
Faculty of Medicine, McGill University, Montreal, QC. Jill R. Johnson is
supported by a Research Fellowship from Imperial College London. Janette
K. Burgess is supported by a National Health & Medical Research Council,
Australia Career Development Fellowship #1032695. Rushita Bagchi is the
recipient of an MHRC/SBRC Coordinated Graduate Studentship awarded by
the Manitoba Health Research Council, Canada.
NR 102
TC 19
Z9 21
U1 1
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1094-5539
J9 PULM PHARMACOL THER
JI Pulm. Pharmacol. Ther.
PD FEB
PY 2013
VL 26
IS 1
BP 42
EP 49
DI 10.1016/j.pupt.2012.08.005
PG 8
WC Pharmacology & Pharmacy; Respiratory System
SC Pharmacology & Pharmacy; Respiratory System
GA 090YE
UT WOS:000315015100006
PM 22939888
ER
PT J
AU Wright, DB
Trian, T
Siddiqui, S
Pascoe, CD
Ojo, OO
Johnson, JR
Dekkers, BGJ
Dakshinamurti, S
Bagchi, R
Burgess, JK
Kanabar, V
AF Wright, David B.
Trian, Thomas
Siddiqui, Sana
Pascoe, Chris D.
Ojo, Oluwaseun O.
Johnson, Jill R.
Dekkers, Bart G. J.
Dakshinamurti, Shyamala
Bagchi, Rushita
Burgess, Janette K.
Kanabar, Varsha
TI Functional phenotype of airway myocytes from asthmatic airways
SO PULMONARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
DE Airway smooth muscle; Vascular smooth muscle; Asthma; Extracellular
matrix; Animal models
ID SMOOTH-MUSCLE-CELLS; EXTRACELLULAR-MATRIX PROTEINS; GROWTH-FACTOR-BETA;
BRONCHIAL EPITHELIAL-CELLS; MYOSIN ISOFORM EXPRESSION; ALLERGIC-ASTHMA;
BASEMENT-MEMBRANE; HUMAN LUNG; RAT LUNG; SM-B
AB In asthma, the airway smooth muscle (ASM) cell plays a central role in disease pathogenesis through cellular changes which may impact on its microenvironment and alter ASM response and function. The answer to the long debated question of what makes a 'healthy' ASM cell become 'asthmatic' still remains speculative. What is known of an 'asthmatic' ASM cell, is its ability to contribute to the hallmarks of asthma such as bronchoconstriction (contractile phenotype), inflammation (synthetic phenotype) and ASM hyperplasia (proliferative phenotype).
The phenotype of healthy or diseased ASM cells or tissue for the most part is determined by expression of key phenotypic markers. ASM is commonly accepted to have different phenotypes: the contractile (differentiated) state versus the synthetic (dedifferentiated) state (with the capacity to synthesize mediators, proliferate and migrate). There is now accumulating evidence that the synthetic functions of ASM in culture derived from asthmatic and non-asthmatic donors differ. Some of these differences include an altered profile and increased production of extracellular matrix proteins, pro-inflammatory mediators and adhesion receptors, collectively suggesting that ASM cells from asthmatic subjects have the capacity to alter their environment, actively participate in repair processes and functionally respond to changes in their microenvironment. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Wright, David B.] Kings Coll London, MRC, London SE1 9NH, England.
[Wright, David B.] Kings Coll London, Asthma UK Ctr Allerg Mech Asthma, London SE1 9NH, England.
[Trian, Thomas] Univ Bordeaux 2, Ctr Rech Cardiothorac Bordeaux, INSERM, U1045,Equipe Remodelage Bronch, F-33076 Bordeaux, France.
[Siddiqui, Sana] McGill Univ, Meakins Christie Labs, Dept Med, Montreal, PQ, Canada.
[Siddiqui, Sana] NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA.
[Pascoe, Chris D.] Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada.
[Ojo, Oluwaseun O.] Univ Manitoba, Dept Resp Physiol, Biol Breathing Grp, Manitoba Inst Child Hlth, Winnipeg, MB, Canada.
[Johnson, Jill R.] Univ London Imperial Coll Sci Technol & Med, Leukocyte Biol Sect, Natl Heart & Lung Inst, London, England.
[Dekkers, Bart G. J.] Univ Groningen, Dept Mol Pharmacol, Groningen Res Inst Asthma, Groningen, Netherlands.
[Dekkers, Bart G. J.] Univ Groningen, COPD, Groningen, Netherlands.
[Dakshinamurti, Shyamala] Univ Manitoba, Sect Neonatol, Womens Hosp WS012, Winnipeg, MB, Canada.
[Bagchi, Rushita] Univ Manitoba, Dept Physiol, Inst Cardiovasc Sci, St Boniface Hosp Res Ctr, Winnipeg, MB, Canada.
[Burgess, Janette K.] Univ Sydney, Cell Biol Grp, Woolcock Inst Med Res, Sydney, NSW 2006, Australia.
[Burgess, Janette K.] Univ Sydney, Discipline Pharmacol, Sydney, NSW 2006, Australia.
[Kanabar, Varsha] Kings Coll London, Sackler Inst Pulm Pharmacol, Div Pharmaceut Sci, London SE1 9NH, England.
RP Kanabar, V (reprint author), Kings Coll London, Sackler Inst Pulm Pharmacol, Div Pharmaceut Sci, 150 Stamford St, London SE1 9NH, England.
EM varsha.kanabar@kcl.ac.uk
RI Burgess, Janette/A-3597-2010;
OI Wright, David/0000-0003-1285-4655; Bagchi, Rushita/0000-0002-9075-0766
FU Alexander McFee Studentship, Faculty of Medicine, McGill University,
Montreal, QC; National Health & Medical Research Council, Australia
Career Development Fellowship [1032695]; Imperial College London Junior
Research Fellowship; MHRC/SBRC Coordinated Graduate Studentship by the
Manitoba Health Research Council, Canada
FX Sana Siddiqui is the recipient of the Alexander McFee Studentship,
Faculty of Medicine, McGill University, Montreal, QC. Janette Burgess is
supported by a National Health & Medical Research Council, Australia
Career Development Fellowship #1032695. Jill R. Johnson is supported by
an Imperial College London Junior Research Fellowship. Rushita Bagchi is
the recipient of an MHRC/SBRC Coordinated Graduate Studentship awarded
by the Manitoba Health Research Council, Canada.
NR 168
TC 5
Z9 6
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1094-5539
J9 PULM PHARMACOL THER
JI Pulm. Pharmacol. Ther.
PD FEB
PY 2013
VL 26
IS 1
BP 95
EP 104
DI 10.1016/j.pupt.2012.08.003
PG 10
WC Pharmacology & Pharmacy; Respiratory System
SC Pharmacology & Pharmacy; Respiratory System
GA 090YE
UT WOS:000315015100011
PM 22921313
ER
PT J
AU Pineda, I
Vazquez, MV
Dagdug, L
AF Pineda, I.
Vazquez, M. -V.
Dagdug, L.
TI Equilibration in two chambers connected by a capillary of arbitrary
shape
SO REVISTA MEXICANA DE FISICA
LA English
DT Article
DE Controlled release; micron-sized vesicle; unbiased diffusion; narrow
channels; Fick-Jacobs' equation
ID CHANNEL; DIFFUSIVITY; TRANSPORT; KINETICS
AB The present work is devoted to the study of the unbiased diffusion of particles to escape from a micron-sized vesicle, through a channel of arbitrary geometry. The use of propagators allows us to describe the diffusion between the vesicle and the interstitial space. The computed relaxation time of the system only depends on its geometric parameters and the diffusion coefficient. It is noted that the whole problem can be reduced to the study of diffusion in the channel. Finally, we give a procedure to find the solution of the Fick-Jacobs' equation for a channel with radial symmetry but arbitrary shape and with constant diffusion coefficient.
C1 [Pineda, I.; Vazquez, M. -V.; Dagdug, L.] Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Mexico City 09340, DF, Mexico.
[Dagdug, L.] NIH, Math & Stat Comp Lab, Bethesda, MD 20892 USA.
RP Pineda, I (reprint author), Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Apartado Postal 55-534, Mexico City 09340, DF, Mexico.
FU National Council of Science and Technology (CONACyT) [27482]
FX I. Pineda wishes to thank the National Council of Science and Technology
(CONACyT) the financial support through grant No. 27482.
NR 32
TC 0
Z9 0
U1 0
U2 3
PU SOC MEXICANA FISICA
PI COYOACAN
PA APARTADO POSTAL 70-348, COYOACAN 04511, MEXICO
SN 0035-001X
J9 REV MEX FIS
JI Rev. Mex. Fis.
PD FEB
PY 2013
VL 59
IS 1
SU S
BP 99
EP 105
PG 7
WC Physics, Multidisciplinary
SC Physics
GA 096SJ
UT WOS:000315424300017
ER
PT J
AU Druz, A
Chen, YC
Guha, R
Betenbaugh, M
Martin, SE
Shiloach, J
AF Druz, Aliaksandr
Chen, Yu-Chi
Guha, Rajarshi
Betenbaugh, Michael
Martin, Scott E.
Shiloach, Joseph
TI Large-scale screening identifies a novel microRNA, miR-15a-3p, which
induces apoptosis in human cancer cell lines
SO RNA BIOLOGY
LA English
DT Article
DE microRNA; Apoptosis; BCL-XL; Caspase; cancer cells
ID HUMAN HEPATOCELLULAR-CARCINOMA; CHEMOTHERAPY-INDUCED APOPTOSIS; BCL-XL;
PROSTATE-CANCER; LUNG-CANCER; ANTISENSE OLIGONUCLEOTIDES; CASPASE
ACTIVATION; MAMMALIAN-CELLS; DOWN-REGULATION; HIT SELECTION
AB MicroRNAs (miRNAs) have been found to be involved in cancer initiation, progression and metastasis and, as such, have been suggested as tools for cancer detection and therapy. In this work, a large-scale screening of the complete miRNA mimics library demonstrated that hsa-miR-15a-3p had a pro-apoptotic role in the following human cancer cells: HeLa, AsPc-1, MDA-MB-231, KB3, ME180, HCT-116 and A549. MiR-15a-3p is a novel member of the pro-apoptotic miRNA cluster, miR-15a/16, which was found to activate Caspase-3/7 and to cause viability loss in B/CMBA. Ov cells during preliminary screening. Subsequent microarrays and bioinformatics analyses identified the following four anti-apoptotic genes: bcl2l1, naip5, fgfr2 and mybl2 as possible targets for the mmu-miR-15a-3p in B/CMBA. Ov cells. Follow-up studies confirmed the pro-apoptotic role of hsa-miR-15a-3p in human cells by its ability to activate Caspase-3/7, to reduce cell viability and to inhibit the expression of bcl2l1 (bcl-x(L)) in HeLa and AsPc-1 cells. MiR-15-3p was also found to reduce viability in HE K293, MDA-MB-231, KB3, ME180, HC T-116 and A549 cell lines and, therefore, may be considered for apoptosis modulating therapies in cancers associated with high Bcl-x(L) expression (cervical, pancreatic, breast, lung and colorectal carcinomas). The capability of hsa-miR-15a-3p to induce apoptosis in these carcinomas may be dependent on the levels of Bcl-x(L) expression. The use of endogenous inhibitors of bcl-x(L) and other anti-apoptotic genes such as hsa-miR-15a-3p may provide improved options for apoptosis-modulating therapies in cancer treatment compared with the use of artificial antisense oligonucleotides.
C1 [Druz, Aliaksandr; Shiloach, Joseph] NIDDKD, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
[Druz, Aliaksandr; Betenbaugh, Michael] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD USA.
[Chen, Yu-Chi; Guha, Rajarshi; Martin, Scott E.] NIH, NIH Chem Genom Ctr, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
RP Shiloach, J (reprint author), NIDDKD, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
EM yossi@nih.gov
RI Betenbaugh, Michael J./A-3252-2010
OI Betenbaugh, Michael J./0000-0002-6336-4659
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
FX Funding was provided by the intramural program of the National Institute
of Diabetes and Digestive and Kidney Diseases, National Institutes of
Health. The authors would like to thank Dr Chithra Keembiyehetty at
NIDDK core lab for performing microarrays and Mrs D. Livnat for critical
editorial assistance.
NR 70
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Z9 18
U1 0
U2 17
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1547-6286
J9 RNA BIOL
JI RNA Biol.
PD FEB
PY 2013
VL 10
IS 2
BP 287
EP 300
DI 10.4161/rna.23339
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 099AR
UT WOS:000315591500014
PM 23353574
ER
PT J
AU Ward, MM
Learch, TJ
Gensler, LS
Davis, JC
Reveille, JD
Weisman, MH
AF Ward, Michael M.
Learch, Thomas J.
Gensler, Lianne S.
Davis, John C., Jr.
Reveille, John D.
Weisman, Michael H.
TI Regional radiographic damage and functional limitations in patients with
ankylosing spondylitis: Differences in early and late disease
SO ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID CERVICAL-SPINE INVOLVEMENT; QUALITY-OF-LIFE; PREDICTIVE FACTORS;
RADIOLOGY INDEX; DISABILITY; MOBILITY; SPONDYLOARTHROPATHIES;
QUESTIONNAIRE; ARTHRITIS; VARIABLES
AB Objective Both radiographic damage and functional limitations increase with the duration of ankylosing spondylitis (AS). We examined whether radiographic damage contributed more to functional limitations in late AS than in early AS, and if the strength of association varied with the anatomic region of damage. Methods In this cross-sectional study of 801 patients with AS, we examined associations of the lumbar modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), the cervical mSASSS, lumbar posterior fusion, cervical posterior fusion, and hip arthritis with the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Health Assessment Questionnaire modified for the spondyloarthritides (HAQ-S). Results Higher lumbar and cervical mSASSS scores were associated with more functional limitations, but there was an interaction between mSASSS scores and the duration of AS, such that the strength of their association with functional limitations decreased with increasing duration of AS. Cervical posterior fusion was associated with worse functioning independent of mSASSS scores. Hip arthritis was significantly associated with functional limitations independent of spinal damage measures. Among patients with AS duration 40 years, the number of comorbid conditions accounted for most of the variation in functioning. Results were similar for both the BASFI and the HAQ-S. Conclusion Although both radiographic damage and functional limitations increase over time in AS, the relative contribution of radiographic damage to functional limitations is lower among patients with longstanding AS than with early AS, suggesting patients may accommodate to limited flexibility. Damage in different skeletal regions impacts functioning over the duration of AS. Functional limitations due to comorbidity supervene in late AS.
C1 [Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Learch, Thomas J.; Weisman, Michael H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Gensler, Lianne S.; Davis, John C., Jr.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Reveille, John D.] Univ Texas Houston, Hlth Sci Ctr, Houston, TX USA.
RP Ward, MM (reprint author), NIAMSD, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
FU NIH/National Institute of Arthritis and Musculoskeletal and Skin
Diseases [PO1-052915, RO1-AR-048465]; Cedars-Sinai General Clinical
Research Center [MO1-RR-00425]; University of Texas at Houston General
Clinical Research Center [MO1-RR-02558]; Rosalind Russell Center for
Arthritis Research at the University of California, San Francisco;
National Institute of Arthritis and Musculoskeletal and Skin
Diseases/NIH
FX Supported by the NIH/National Institute of Arthritis and Musculoskeletal
and Skin Diseases (grants PO1-052915 and RO1-AR-048465), the
Cedars-Sinai General Clinical Research Center (MO1-RR-00425), the
University of Texas at Houston General Clinical Research Center
(MO1-RR-02558), The Rosalind Russell Center for Arthritis Research at
the University of California, San Francisco, and the Intramural Research
Program, National Institute of Arthritis and Musculoskeletal and Skin
Diseases/NIH.
NR 41
TC 5
Z9 6
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2151-464X
J9 ARTHRIT CARE RES
JI Arthritis Care Res.
PD FEB
PY 2013
VL 65
IS 2
BP 257
EP 265
DI 10.1002/acr.21821
PG 9
WC Rheumatology
SC Rheumatology
GA 083LW
UT WOS:000314466600012
PM 23042639
ER
PT J
AU Jarcho, JM
Fox, NA
Pine, DS
Etkin, A
Leibenluft, E
Shechner, T
Ernst, M
AF Jarcho, Johanna M.
Fox, Nathan A.
Pine, Daniel S.
Etkin, Amit
Leibenluft, Ellen
Shechner, Tomer
Ernst, Monique
TI The neural correlates of emotion-based cognitive control in adults with
early childhood behavioral inhibition
SO BIOLOGICAL PSYCHOLOGY
LA English
DT Article
DE Behavioral inhibition; Conflict detection; Conflict adaptation; Emotion
regulation; fMRI; Development
ID GENERALIZED ANXIETY DISORDER; ANTERIOR CINGULATE CORTEX; ERROR-RELATED
NEGATIVITY; PSYCHOMETRIC PROPERTIES; DEPRESSIVE-DISORDERS; IMPLICIT
REGULATION; BRAIN ACTIVATION; CONFLICT; ADOLESCENTS; ATTENTION
AB The present study is the first to assess whether the neural correlates of cognitive control processes differ in adults with and without a behaviorally inhibited temperament during early childhood. Adults with and without childhood behavioral inhibition completed an emotional conflict task while undergoing functional magnetic resonance imaging scanning. While no group differences in behavior were observed, adults with childhood behavioral inhibition, relative to adults without childhood behavioral inhibition, exhibited greater dorsomedial prefrontal cortex activity during conflict detection and greater putamen activity during conflict adaptation. Lifetime psychopathology predicted behavioral, but not brain-related, differences in conflict adaptation. These data suggest that the brain regions underlying cognitive control processes are differentially influenced by childhood behavioral inhibition, and may be differently related to psychopathology. Published by Elsevier B.V.
C1 [Jarcho, Johanna M.; Pine, Daniel S.; Shechner, Tomer; Ernst, Monique] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA.
[Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA.
[Etkin, Amit] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Etkin, Amit] Vet Affairs Palo Alto Hlth Care Syst, Sierra Pacific Mental Illness Res Educ & Clin Ctr, Palo Alto, CA USA.
[Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Bethesda, MD 20892 USA.
RP Jarcho, JM (reprint author), NIMH, Sect Dev & Affect Neurosci, NIH, 9000 Rockville Pike,Bldg 15K, Bethesda, MD 20892 USA.
EM johanna.jarcho@nih.gov
OI Jarcho, Johanna/0000-0001-9075-6968
FU Intramural Research Program of the National Institute of Health;
National Institute of Mental Health [NAF: R01 MH 074454]; National
Institute of Child Health and Development [NAF: 5R37 HD 017899-20]
FX This work was supported by the Intramural Research Program of the
National Institute of Health, and grants from the National Institute of
Mental Health Grant (NAF: R01 MH 074454) and the National Institute of
Child Health and Development Grant (NAF: 5R37 HD 017899-20).
NR 51
TC 26
Z9 26
U1 2
U2 26
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0301-0511
J9 BIOL PSYCHOL
JI Biol. Psychol.
PD FEB
PY 2013
VL 92
IS 2
BP 306
EP 314
DI 10.1016/j.biopsycho.2012.09.008
PG 9
WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology,
Experimental
SC Psychology; Behavioral Sciences
GA 095DU
UT WOS:000315315700029
PM 23046903
ER
PT J
AU Linhares, YPL
Pavletic, S
Gale, RP
AF Linhares, Y. P. L.
Pavletic, S.
Gale, R. P.
TI Chronic GVHD: Where are we? Where do we want to be? Will
immunomodulatory drugs help?
SO BONE MARROW TRANSPLANTATION
LA English
DT Review
DE Chronic GVHD; IMiDs; thalidomide; lenalidomide; pomalidomide
ID VERSUS-HOST-DISEASE; CONSENSUS DEVELOPMENT PROJECT; WORKING
GROUP-REPORT; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION;
CD4(+) T-CELLS; CHRONIC GRAFT; CLINICAL-TRIALS; THERAPEUTIC RESPONSE;
THALIDOMIDE ANALOG
AB Chronic GVHD (cGVHD) is an important problem after allotransplants. Some risk factors for cGVHD are similar to those of acute GVHD (aGVHD) but others are distinct indicating sometimes overlapping but unique pathogeneses. Precise incidence and prevalence data of cGVHD are lacking because of diverse diagnostic criteria but a 50% risk is a reasonable estimate. Incidence and prevalence of cGVHD are probably growing because of increased use of unrelated donors, blood rather than bone marrow (BM) grafts, decreased early transplant-related mortality (TRM) and increasing frequency of allotransplants. Pathophysiology of cGVHD is complex and poorly understood. Notably, no reliable surrogate end point to predict mechanism(s) of cGVHD has been identified. Therapy of cGVHD is unsatisfactory. Corticosteroids are effective but other drugs are controversial and few are rigorously tested in randomized trials. Highly variable response rates are reported because of small sample sizes and inconsistencies in eligibility, diagnostic and response criteria. We focus on the possible role of immunomodulatory drugs (IMiDs), thalidomide lenalidomide and pomalidomide, in preventing and treating cGVHD. The data suggest activity of thalidomide but at doses not clinically practical in many instances. There are few data with lenalidomide. Trials of pomalidomide, which has immune activities like thalidomide but with fewer adverse effects, are beginning. Because cGVHD is not recently reviewed in Bone Marrow Transplantation, we give a brief background and discuss challenges in diagnosing, understanding and treating cGVHD including the recently proposed National Institutes of Health consensus criteria for cGVHD. Bone Marrow Transplantation (2013) 48, 203-209; doi:10.1038/bmt.2012.76; published online 14 May 2012
C1 [Linhares, Y. P. L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Med Oncol, Los Angeles, CA 90095 USA.
[Pavletic, S.] NCI, GVHD & Autoimmun Unit, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
[Gale, R. P.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Sect Haematol, Div Expt Med, London, England.
RP Gale, RP (reprint author), Imperial Coll, Dept Med, Sect Haematol, Div Expt Med, 11693 San Vicente Blvd,Suite 335, Los Angeles, CA 90049 USA.
EM robertpetergale@aol.com
FU NIHR Biomedical Research Centre; NCI; Celgene [02328]
FX RPG acknowledges support from the NIHR Biomedical Research Centre
funding scheme. Statements included in this article do not represent the
official position of the NCI, NIH or the US government. SZP receives
partial research funding support through the Cooperative Research and
Development Agreement for intramural-PHS clinical research executed
between the NCI and Celgene (CRADA #02328). Our many collaborators over
several decades, especially who criticized us and making us better
scientists and clinicians and this a better typescript. Special thanks
to Iskra Pusic (Washington Univerity, St Louis, MO) and Lana Grkovic
(Rebro University Hospital, Zagreb, Croatia) for their input to an
earlier review section of this typescript. Hillard M Lazarus (Case
Western Reserve University, Celevland, OH) suggested a review of cGVHD
and IMiDs and provided many helpful comments.
NR 91
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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 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD FEB
PY 2013
VL 48
IS 2
BP 203
EP 209
DI 10.1038/bmt.2012.76
PG 7
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 094BY
UT WOS:000315239200013
PM 22580766
ER
PT J
AU Foglietta, M
Neelapu, SS
Kwak, LW
Jiang, Y
Nattamai, D
Lee, ST
Fowler, DH
Sportes, C
Gress, RE
Steinberg, SM
Vence, LM
Radvanyi, L
Dwyer, KC
Qazilbash, MH
Bryant, RNK
Bishop, MR
AF Foglietta, M.
Neelapu, S. S.
Kwak, L. W.
Jiang, Y.
Nattamai, D.
Lee, S-T
Fowler, D. H.
Sportes, C.
Gress, R. E.
Steinberg, S. M.
Vence, L. M.
Radvanyi, L.
Dwyer, K. C.
Qazilbash, M. H.
Bryant, R. N. K.
Bishop, M. R.
TI Neoantigen and tumor antigen-specific immunity transferred from
immunized donors is detectable early after allogeneic transplantation in
myeloma patients
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE myeloma; allogeneic; donor vaccination; idiotype
ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; REGULATORY
T-CELLS; INFLUENZAE TYPE-B; MULTIPLE-MYELOMA; PERIPHERAL-BLOOD; IDIOTYPE
VACCINATION; FOLLICULAR LYMPHOMA; DENDRITIC CELLS; RESPONSES
AB To enhance the therapeutic index of allogeneic hematopoietic SCT (HSCT), we immunized 10 HLA-matched sibling donors before stem cell collection with recipient-derived clonal myeloma Ig, idiotype (Id), as a tumor antigen, conjugated with keyhole limpet hemocyanin (KLH). Vaccinations were safe in donors and recipients. Donor-derived KLH- and Id-specific humoral and central and effector memory T-cell responses were detectable by day 30 after HSCT and were boosted by post-transplant vaccinations at 3 months in most recipients. One patient died before booster vaccinations. Specifically, after completing treatment, 8/9 myeloma recipients had persistent Id-specific immune responses and 5/9 had improvement in disease status. Although regulatory T cells increased after vaccination, they did not impact immune responses. At a median potential follow-up period of 74 months, 6 patients are alive, the 10 patients have a median PFS of 28.5 months and median OS has not been reached. Our results provide proof of principle that neoantigen and tumor antigen-specific humoral and cellular immunity could be safely induced in HSCT donors and passively transferred to recipients. This general strategy may be used to reduce relapse of malignancies and augment protection against infections after allogeneic HSCT. Bone Marrow Transplantation (2013) 48, 269-277; doi:10.1038/bmt.2012.132; published online 9 July 2012
C1 [Foglietta, M.; Neelapu, S. S.; Kwak, L. W.; Jiang, Y.; Nattamai, D.; Lee, S-T] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Div Canc Med, Houston, TX 77030 USA.
[Foglietta, M.; Neelapu, S. S.; Kwak, L. W.; Jiang, Y.; Nattamai, D.; Lee, S-T; Vence, L. M.; Radvanyi, L.; Dwyer, K. C.] Univ Texas MD Anderson Canc Ctr, Ctr Canc Immunol Res, Houston, TX 77030 USA.
[Fowler, D. H.; Sportes, C.; Gress, R. E.; Bryant, R. N. K.; Bishop, M. R.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Steinberg, S. M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Rockville, MD USA.
[Vence, L. M.; Radvanyi, L.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Div Canc Med, Houston, TX 77030 USA.
[Dwyer, K. C.; Qazilbash, M. H.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Div Canc Med, Houston, TX 77030 USA.
RP Kwak, LW (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Div Canc Med, 1515 Holcombe Blvd,Unit 429, Houston, TX 77030 USA.
EM lkwak@mdanderson.org
FU Center for Cancer Research, the National Cancer Institute, the National
Institutes of Health; Leukemia and Lymphoma Society (Specialized Center
of Research) [7262-08]; National Institutes of Health [R21 CA123860,
K23CA123149]; Gateway Foundation; American Society of Clinical Oncology
Career Development Award; American Society of Hematology Junior Faculty
Scholar Award in Clinical/Translational Research; Doris Duke Charitable
Foundation Clinical Scientist Development Award; Cancer Center Support
Grant [CA16672]
FX This work was supported by the Center for Cancer Research, the National
Cancer Institute, the National Institutes of Health; the Leukemia and
Lymphoma Society (Specialized Center of Research Grant No. 7262-08
(LWK)); the National Institutes of Health Grant R21 CA123860 (LWK); the
Gateway Foundation (LWK); the American Society of Clinical Oncology
Career Development Award (SSN); the American Society of Hematology
Junior Faculty Scholar Award in Clinical/Translational Research (SSN);
the National Institutes of Health Grant K23CA123149 (SSN); and the Doris
Duke Charitable Foundation Clinical Scientist Development Award (SSN).
The Immune Monitoring Core Facility and the Flow Cytometry Core Facility
at the MD Anderson Cancer Center are supported by the Cancer Center
Support Grant CA16672 (National Institutes of Health).
NR 41
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U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD FEB
PY 2013
VL 48
IS 2
BP 269
EP 277
DI 10.1038/bmt.2012.132
PG 9
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 094BY
UT WOS:000315239200024
PM 22773122
ER
PT J
AU Johnson, LM
Price, DK
Figg, WD
AF Johnson, Linda M.
Price, Douglas K.
Figg, William D.
TI Treatment-induced secretion of WNT16B promotes tumor growth and acquired
resistance to chemotherapy Implications for potential use of inhibitors
in cancer treatment
SO CANCER BIOLOGY & THERAPY
LA English
DT Editorial Material
DE prostate cancer; WNT16B; chemotherapy resistance; tumor
microenvironment; NF kappa B; cytotoxic drugs; DNA damage response
program
ID DRUG-RESISTANCE
C1 [Johnson, Linda M.; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA.
[Figg, William D.] NCI, Clin Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA.
EM figgw@helix.nih.gov
RI Figg Sr, William/M-2411-2016
NR 6
TC 5
Z9 6
U1 1
U2 12
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD FEB
PY 2013
VL 14
IS 2
BP 90
EP 91
DI 10.4161/cbt.22636
PG 2
WC Oncology
SC Oncology
GA 083MP
UT WOS:000314468700003
PM 23114711
ER
PT J
AU Ierano, C
Basseville, A
To, KKW
Zhan, ZR
Robey, RW
Wilkerson, J
Bates, SE
Scala, S
AF Ierano, Caterina
Basseville, Agnes
To, Kenneth K. W.
Zhan, Zhirong
Robey, Robert W.
Wilkerson, Julia
Bates, Susan E.
Scala, Stefania
TI Histone deacetylase inhibitors induce CXCR4 mRNA but antagonize CXCR4
migration
SO CANCER BIOLOGY & THERAPY
LA English
DT Article
DE CXCR4; CXCL12; histone deacetylase inhibitor; romidepsin; migration
ID RENAL-CELL-CARCINOMA; BREAST-CANCER CELLS; CHEMOKINE RECEPTOR; VALPROIC
ACID; DEPSIPEPTIDE FR901228; LUNG-CANCER; UP-REGULATION; TUMOR-CELLS;
EXPRESSION; ACTIVATION
AB The stromal cell-derived factor-1 alpha SDF-1 alpha (CXCL12)/CXCR4 axis has been linked to poor prognosis in some cancers. As histone deacetylase inhibitors (HDIs) exert antitumor effects by targeting proteins affecting cell migration, we sought to evaluate the effects of the HDIs apicidin, vorinostat, entinostat (MS-275) and romidepsin on the expression and function of CXCR4 in human cancer cell lines. After treatment with romidepsin, CXCR4 mRNA expression increased 12-fold in UOK121 renal cancer cells, 16-fold in H460 non-small cell cancer cells and 4-fold in SF295 glioma cells; treatment with other HDIs yielded similar effects. CXCR4 induction was not observed in MCF7 breast cancer cells or SW620 colon cancer cells. To evaluate the corresponding functional increase, the effect of CXCR4 ligand, CXCL12, on ERK1/2, STAT3 and c-SRC activation and cell migration was examined in UOK121, SF295 and H460 cells. Alone, the HDIs increased pERK1/2, while reducing pSTAT-3 and pSRC. Following CXCL12 exposure, pERK1/2 induction was maintained, but STAT3 and SRC phosphorylation was impaired. These findings resulted in reduced basal and CXCL12-mediated cell migration. In conclusion, HDIs upregulated CXCR4 mRNA expression but impaired CXCL12-dependent signaling cascades through STAT3 and c-SRC, suggesting a potential role for HDIs in delaying or preventing metastatic processes in solid tumors.
C1 [Ierano, Caterina; Basseville, Agnes; To, Kenneth K. W.; Zhan, Zhirong; Robey, Robert W.; Wilkerson, Julia; Bates, Susan E.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Ierano, Caterina; Scala, Stefania] G Pascale Fdn, Natl Canc Inst Naples, Naples, Italy.
RP Robey, RW (reprint author), NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
EM robeyr@mail.nih.gov
RI To, Kenneth /M-4500-2013; Scala, Stefania/K-1380-2016; Ierano,
Caterina/K-1676-2016;
OI To, Kenneth /0000-0003-2755-0283; Scala, Stefania/0000-0001-9524-2616;
Ierano, Caterina/0000-0003-3138-1873; Wilkerson,
Julia/0000-0002-6965-0867
FU Intramural Research Program of the National Cancer Institute; CRADA
FX This work was supported in part by the Intramural Research Program of
the National Cancer Institute. This work was supported in part by a
CRADA between the NCI and Celgene Corp.
NR 48
TC 3
Z9 3
U1 0
U2 6
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD FEB
PY 2013
VL 14
IS 2
BP 175
EP 183
DI 10.4161/cbt.22957
PG 9
WC Oncology
SC Oncology
GA 083MP
UT WOS:000314468700014
PM 23192271
ER
PT J
AU Wentzensen, N
Wacholder, S
AF Wentzensen, Nicolas
Wacholder, Sholom
TI From Differences in Means between Cases and Controls to Risk
Stratification: A Business Plan for Biomarker Development
SO CANCER DISCOVERY
LA English
DT Review
ID OVARIAN-CANCER; PERFORMANCE; MARKER; TESTS
AB Researchers developing biomarkers for early detection can determine the potential for clinical benefit at early stages of development. We provide the theoretical background showing the quantitative connection between biomarker levels in cases and controls and clinically meaningful risk measures, as well as a spreadsheet for researchers to use in their own research. We provide researchers with tools to decide whether a test is useful, whether it needs technical improvement, whether it may work only in specific populations, or whether any further development is futile. The methods described here apply to any method that aims to estimate risk of disease based on biomarkers, clinical tests, genetics, environment, or behavior.
Significance: Many efforts go into futile biomarker development and premature clinical testing. In many instances, predictions for translational success or failure can be made early, simply based on critical analysis of case-control data. Our article presents well-established theory in a form that can be appreciated by biomarker researchers. Furthermore, we provide an interactive spreadsheet that links biomarker performance with specific disease characteristics to evaluate the promise of biomarker candidates at an early stage. Cancer Discov; 3(2); 148-57. (C) 2012 AACR.
C1 [Wentzensen, Nicolas; Wacholder, Sholom] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
RP Wacholder, S (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 5050, Rockville, MD 20852 USA.
EM WacholdS@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute.
NR 13
TC 23
Z9 23
U1 0
U2 12
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
J9 CANCER DISCOV
JI Cancer Discov.
PD FEB
PY 2013
VL 3
IS 2
BP 148
EP 157
DI 10.1158/2159-8290.CD-12-0196
PG 10
WC Oncology
SC Oncology
GA 088IA
UT WOS:000314826300021
PM 23299199
ER
PT J
AU Fox, ER
Musani, SK
Barbalic, M
Lin, HH
Yu, B
Ogunyankin, KO
Smith, NL
Kutlar, A
Glazer, NL
Post, WS
Paltoo, DN
Dries, DL
Farlow, DN
Duarte, CW
Kardia, SL
Meyers, KJ
Sun, YV
Arnett, DK
Patki, AA
Sha, J
Cui, XQ
Samdarshi, TE
Penman, AD
Bibbins-Domingo, K
Buzkova, P
Benjamin, EJ
Bluemke, DA
Morrison, AC
Heiss, G
Carr, JJ
Tracy, RP
Mosley, TH
Taylor, HA
Psaty, BM
Heckbert, SR
Cappola, TP
Vasan, RS
AF Fox, Ervin R.
Musani, Solomon K.
Barbalic, Maja
Lin, Honghuang
Yu, Bing
Ogunyankin, Kofo O.
Smith, Nicholas L.
Kutlar, Abdullah
Glazer, Nicole L.
Post, Wendy S.
Paltoo, Dina N.
Dries, Daniel L.
Farlow, Deborah N.
Duarte, Christine W.
Kardia, Sharon L.
Meyers, Kristin J.
Sun, Yan V.
Arnett, Donna K.
Patki, Amit A.
Sha, Jin
Cui, Xiangqui
Samdarshi, Tandaw E.
Penman, Alan D.
Bibbins-Domingo, Kirsten
Buzkova, Petra
Benjamin, Emelia J.
Bluemke, David A.
Morrison, Alanna C.
Heiss, Gerardo
Carr, J. Jeffrey
Tracy, Russell P.
Mosley, Thomas H.
Taylor, Herman A.
Psaty, Bruce M.
Heckbert, Susan R.
Cappola, Thomas P.
Vasan, Ramachandran S.
TI Genome-Wide Association Study of Cardiac Structure and Systolic Function
in African Americans The Candidate Gene Association Resource (CARe)
Study
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE echocardiography; ethnic; genome-wide association studies; left atrium
genetics; left ventricular mass genetics
ID LEFT-VENTRICULAR MASS; COMMON DISEASES; HYPERTROPHY; VARIANTS;
SUSCEPTIBILITY; CONTRACTILITY; HYPERTENSION; HYPERGEN; LINKAGE; MARKERS
AB Background-Using data from 4 community-based cohorts of African Americans, we tested the association between genome-wide markers (single-nucleotide polymorphisms) and cardiac phenotypes in the Candidate-gene Association Resource study.
Methods and Results-Among 6765 African Americans, we related age, sex, height, and weight-adjusted residuals for 9 cardiac phenotypes (assessed by echocardiogram or magnetic resonance imaging) to 2.5 million single-nucleotide polymorphisms genotyped using Genome-wide Affymetrix Human SNP Array 6.0 (Affy6.0) and the remainder imputed. Within the cohort, genome-wide association analysis was conducted, followed by meta-analysis across cohorts using inverse variance weights (genome-wide significance threshold=4.0x10(-7)). Supplementary pathway analysis was performed. We attempted replication in 3 smaller cohorts of African ancestry and tested lookups in 1 consortium of European ancestry (EchoGEN). Across the 9 phenotypes, variants in 4 genetic loci reached genome-wide significance: rs4552931 in UBE2V2 (P=1.43x10(-7)) for left ventricular mass, rs7213314 in WIPI1 (P=1.68x10(-7)) for left ventricular internal diastolic diameter, rs1571099 in PPAPDC1A (P=2.57x10(-8)) for interventricular septal wall thickness, and rs9530176 in KLF5 (P=4.02x10(-7)) for ejection fraction. Associated variants were enriched in 3 signaling pathways involved in cardiac remodeling. None of the 4 loci replicated in cohorts of African ancestry was confirmed in lookups in EchoGEN.
Conclusions-In the largest genome-wide association study of cardiac structure and function to date in African Americans, we identified 4 genetic loci related to left ventricular mass, interventricular septal wall thickness, left ventricular internal diastolic diameter, and ejection fraction, which reached genome-wide significance. Replication results suggest that these loci may be unique to individuals of African ancestry. Additional large-scale studies are warranted for these complex phenotypes. (Circ Cardiovasc Genet. 2013;6:37-46.)
C1 [Fox, Ervin R.; Musani, Solomon K.; Yu, Bing; Samdarshi, Tandaw E.; Penman, Alan D.; Mosley, Thomas H.; Taylor, Herman A.] Univ Mississippi, Sch Med, Dept Med, Jackson, MS 39216 USA.
[Barbalic, Maja; Morrison, Alanna C.] Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA.
[Lin, Honghuang; Glazer, Nicole L.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Ogunyankin, Kofo O.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Sch Med, Seattle, WA 98195 USA.
[Smith, Nicholas L.] US Dept Vet Affairs, Seattle Epidemiol Res & Informat Ctr, Off Res & Dev, Grp Hlth Res Inst,Grp Hlth Cooperat, Seattle, WA USA.
[Kutlar, Abdullah] Georgia Hlth Sci Univ, Dept Med, Augusta, GA USA.
[Post, Wendy S.] Johns Hopkins Sch Med, Dept Med, Div Cardiol, Baltimore, MD USA.
[Paltoo, Dina N.] NHLBI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Dries, Daniel L.] Yale Univ, Sch Med, Dept Med, Div Cardiovasc, New Haven, CT 06510 USA.
[Farlow, Deborah N.] Broad Inst Massachusetts Inst Technol & Harvard U, Boston, MA USA.
[Duarte, Christine W.; Patki, Amit A.; Cui, Xiangqui] Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA.
[Arnett, Donna K.; Sha, Jin] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Kardia, Sharon L.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Meyers, Kristin J.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA.
[Sun, Yan V.] Emory Univ, Sch Med, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA USA.
[Bibbins-Domingo, Kirsten] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Buzkova, Petra] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Carr, J. Jeffrey] Wake Forest Univ, Sch Med Publ Hlth & Translat Sci, Salem, NC USA.
[Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol & Lab Med, Burlington, VT 05405 USA.
[Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Carr, J. Jeffrey] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
RP Fox, ER (reprint author), Univ Mississippi, Med Ctr, Dept Med, 2500 North State St, Jackson, MS 39216 USA.
EM efox@medicine.umsmed.edu
RI Carr, John/A-1938-2012;
OI Carr, John/0000-0002-4398-8237; Lin, Honghuang/0000-0003-3043-3942;
Ramachandran, Vasan/0000-0001-7357-5970; Benjamin,
Emelia/0000-0003-4076-2336; Bluemke, David/0000-0002-8323-8086
FU National Institutes of Health (NIH)/National Institute on Minority
Health and Health Disparities (NIMHD) [P20]; Novartis; Celgene Corp;
Global Iron Summit; NIH [HL 100245, R01 HL09257, RC1 HD101056, R01
HL102214, R01 AG028321]; Candidate Gene Association Resource Study,
Exome Sequencing Project; ARIC, NIH; NIH; National Heart, Lung, and
Blood Institute [HL 087652]; University of North Carolina at Chapel Hill
[N01-HC-55015]; Baylor Medical College [N01-HC-55016]; University of
Mississippi Medical Center [N01-HC-55021]; University of Minnesota
[N01-HC-55019, N01-HC-48048]; Johns Hopkins University [N01-HC-55020,
N01-HC-85081, N01 HC-15103]; University of Texas, Houston
[N01-HC-55017]; University of North Carolina, Forsyth County
[N01-HC-55018]; University of Washington [N01-HC-85079, N01 HC-55222,
U01 HL080295, N01-HC-95159]; Wake Forest University [N01-HC-85080,
N01-HC-45205]; University of Pittsburgh [N01-HC-85082]; University of
California, Davis [N01-HC-85083]; University of California, Irvine
[N01-HC-85084, N01-HC-45134, N01-HC-95100]; New England Medical Center
[N01-HC-85085]; University of Vermont [N01-HC-85086]; Georgetown
University [N01-HC-35129]; University of Wisconsin [N01-HC-75150];
Geisinger Clinic [N01-HC-45133]; Case Western Reserve University [RO1
HL46380-01-16]; University of Illinois [N01-HB-72982, N01-HB-97062];
Howard University [N01-HB-72991, N01-HB-97061]; University of Miami
[N01-HB-72992, N01-HB-97064]; Duke University [N01-HB-72993]; George
Washington University [N01-HB-72994]; University of Tennessee
[N01-HB-72995, N01-HB-97070]; Yale University [N01-HB-72996,
N01-HB-97072]; Children's Hospital-Philadelphia [N01-HB-72997,
N01-HB-97056]; University of Chicago [N01-HB-72998, N01-HB-97053];
Medical College of Georgia [N01-HB-73000, N01-HB-97060]; Washington
University [N01-HB-73001, N01-HB-97071]; Jewish Hospital and Medical
Center of Brooklyn [N01-HB-73002]; Trustees of Health and Hospitals of
the City of Boston, Inc. [N01-HB-73003]; Children's Hospital-Oakland
[N01-HB-73004, N01-HB-97054]; University of Mississippi [N01-HB-73005,
N01-HC-95171]; St. Luke's Hospital-New York [N01-HB-73006]; Alta
Bates-Herrick Hospital [N01-HB-97051]; Columbia University
[N01-HB-97058]; St. Jude's Children's Research Hospital [N01-HB-97066];
Research Foundation, State University of New York-Albany [N01-HB-97068,
N01-HB-97069]; New England Research Institute [N01-HB-97073]; Interfaith
Medical Center-Brooklyn [N01-HB-97085]; University of Alabama at
Birmingham [N01-HC-48047, N01-HC-95095]; Northwestern University
[N01-HC-48049]; Kaiser Foundation Research Institute [N01-HC-48050];
Tufts-New England Medical Center [N01-HC-45204]; Harbor-UCLA Research
and Education Institute [N01-HC-05187]; Boston University
[N01-HC-25195]; Jackson State University [N01-HC-95170]; Tougaloo
College [N01-HC-95172]; Regents of the University of California
[N01-HC-95160]; [R01 HD067264]; [RC4 AG039029]; [R01 HL101161-01-A1];
[R01 DK077950-03]; [RC1 HL100185]; [P60 MD002249]
FX Dr Kutlar received research grants from National Institutes of Health
(NIH)/National Institute on Minority Health and Health Disparities
(NIMHD)-P20, Novartis, Celgene Corp. (>=$10000), and Global Iron Summit
(<$10000). Dr Paltoo has ownership interest in a 529 College Plan and a
Thrift Saving Plan (>$10000). Dr Kardia received research grants from
R01 HD067264, RC4 AG039029, R01 HL101161-01-A1, R01 DK077950-03, RC1
HL100185, and P60 MD002249 (>$10000). Dr Sun received research grants
from NIH HL 100245, Genetics of Hypertension Risk Factors, and Sequela
in African Americans (>$10000). Dr Benjamin received research grants
from R01 HL09257, RC1 HD101056, R01 HL102214, and R01 AG028321 (all NIH
grants >$10000). Dr Tracy received research grants from Candidate Gene
Association Resource Study, Exome Sequencing Project (>$10000). Dr
Mosley received research grants from ARIC, ARIC-Neurocognitive Study,
Predictors of Coronary Artery Calcification in an African American
Cohort, GWAS of Ischemic Brain Vascular Injury, ARIC PET Amyloid Imaging
Study, the Intracranial Atherosclerosis Disease and Cognitive Impairment
Study, Parkinson Disease and Olfactory Function in the ARIC Study, and
Identify Epidemiological Risk Factors for Abdominal Aortic Aneurysm
Study (all NIH grants >$10000). Dr Taylor received research grants for
the Jackson Heart Study (NIH grant >$10000). Dr Psaty received NIH
grants (<$10000); he serves on the Data and Safety Monitoring Board for
a clinical trial for a device (Zoll Life Cor <$10000) and service on the
Steering Committee for Yale Open Data Project (Medtronic <$10000). Dr
Heckbert received research grants from HL 087652 Whole Genome
Association Study in the Cardiovascular Health Study (National Heart,
Lung, and Blood Institute >$10000). Dr Vasan received an NIH grant
(>$10000). The other authors report no conflicts.; Atherosclerotic Risk
in Communities: University of North Carolina at Chapel Hill
(N01-HC-55015), Baylor Medical College (N01-HC-55016), University of
Mississippi Medical Center (N01-HC-55021), University of Minnesota
(N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of
Texas, Houston (N01-HC-55017), and University of North Carolina, Forsyth
County (N01-HC-55018); Cardiovascular Health Study: University of
Washington (N01-HC-85079), Wake Forest University (N01-HC-85080), Johns
Hopkins University (N01-HC-85081), University of Pittsburgh
(N01-HC-85082), University of California, Davis (N01-HC-85083),
University of California, Irvine (N01-HC-85084), New England Medical
Center (N01-HC-85085), University of Vermont (N01-HC-85086), Georgetown
University (N01-HC-35129), Johns Hopkins University (N01 HC-15103),
University of Wisconsin (N01-HC-75150), Geisinger Clinic (N01-HC-45133),
and University of Washington (N01 HC-55222, U01 HL080295); Cleveland
Family Study: Case Western Reserve University (RO1 HL46380-01-16);
Cooperative Study of Sickle Cell Disease: University of Illinois
(N01-HB-72982, N01-HB-97062), Howard University (N01-HB-72991,
N01-HB-97061), University of Miami (N01-HB-72992, N01-HB-97064), Duke
University (N01-HB-72993), George Washington University (N01-HB-72994),
University of Tennessee (N01-HB-72995, N01-HB-97070), Yale University
(N01-HB-72996, N01-HB-97072), Children's Hospital-Philadelphia
(N01-HB-72997, N01-HB-97056), University of Chicago (N01-HB-72998,
N01-HB-97053), Medical College of Georgia (N01-HB-73000, N01-HB-97060),
Washington University (N01-HB-73001, N01-HB-97071), Jewish Hospital and
Medical Center of Brooklyn (N01-HB-73002), Trustees of Health and
Hospitals of the City of Boston, Inc. (N01-HB-73003), Children's
Hospital-Oakland (N01-HB-73004, N01-HB-97054), University of Mississippi
(N01-HB-73005), St. Luke's Hospital-New York (N01-HB-73006), Alta
Bates-Herrick Hospital (N01-HB-97051), Columbia University
(N01-HB-97058), St.; Jude's Children's Research Hospital (N01-HB-97066),
Research Foundation, State University of New York-Albany (N01-HB-97068,
N01-HB-97069), New England Research Institute (N01-HB-97073), and
Interfaith Medical Center-Brooklyn (N01-HB-97085); Coronary Artery Risk
in Young Adults: University of Alabama at Birmingham (N01-HC-48047),
University of Minnesota (N01-HC-48048), Northwestern University
(N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050),
University of Alabama at Birmingham (N01-HC-95095), Tufts-New England
Medical Center (N01-HC-45204), Wake Forest University (N01-HC-45205),
Harbor-UCLA Research and Education Institute (N01-HC-05187), and
University of California, Irvine (N01-HC-45134, N01-HC-95100);
Framingham Heart Study: Boston University (N01-HC-25195); Jackson Heart
Study: Jackson State University (N01-HC-95170), University of
Mississippi (N01-HC-95171), and Tougaloo College (N01-HC-95172);
Multi-Ethnic Study of Atherosclerosis: University of Washington
(N01-HC-95159), Regents of the University of California (N01-HC-95160),
Columbia University (N01-HC-95161), Johns Hopkins University
(N01-HC-95162), University of Minnesota (N01-HC-95163), Northwestern
University (N01-HC-95164), Wake Forest University (N01-HC-95165),
University of Vermont (N01-HC-95166), New England Medical Center
(N01-HC-95167), Johns Hopkins University (N01-HC-95168), and Harbor-UCLA
Research and Education Institute (N01-HC-95169); Sleep Heart Health
Study: Johns Hopkins University (U01 HL064360), Case Western University
(U01 HL063463), University of California, Davis (U01 HL053916),
University of Arizona (U01 HL053938), University of Minnesota
(relocating in 2006 to University Arizona) (U01 HL053934), University of
Pittsburgh (U01 HL077813), Boston University (U01 HL053941), MedStar
Research Institute (U01 HL063429), and Johns Hopkins University (U01
HL053937).
NR 28
TC 15
Z9 15
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD FEB
PY 2013
VL 6
IS 1
BP 37
EP 46
DI 10.1161/CIRCGENETICS.111.962365
PG 10
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 094YL
UT WOS:000315301500008
PM 23275298
ER
PT J
AU Yu, B
Barbalic, M
Brautbar, A
Nambi, V
Hoogeveen, RC
Tang, WH
Mosley, TH
Rotter, JI
deFilippi, CR
O'Donnell, CJ
Kathiresan, S
Rice, K
Heckbert, SR
Ballantyne, CM
Psaty, BM
Boerwinkle, E
AF Yu, Bing
Barbalic, Maja
Brautbar, Ariel
Nambi, Vijay
Hoogeveen, Ron C.
Tang, Weihong
Mosley, Thomas H.
Rotter, Jerome I.
deFilippi, Christopher R.
O'Donnell, Christopher J.
Kathiresan, Sekar
Rice, Ken
Heckbert, Susan R.
Ballantyne, Christie M.
Psaty, Bruce M.
Boerwinkle, Eric
CA CARDIoGRAM Consortium
TI Association of Genome-Wide Variation With Highly Sensitive Cardiac
Troponin-T Levels in European Americans and Blacks A Meta-Analysis From
Atherosclerosis Risk in Communities and Cardiovascular Health Studies
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE genetics; genome-wide association study; troponin
ID CORONARY-ARTERY-DISEASE; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; SARCOMERE
PROTEIN GENES; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION;
ALPHA-TROPOMYOSIN; HEART-FAILURE; MUTATIONS; ASSAY; MORTALITY
AB Background-High levels of cardiac troponin T, measured by a highly sensitive assay (hs-cTnT), are strongly associated with incident coronary heart disease and heart failure. To date, no large-scale genome-wide association study of hs-cTnT has been reported. We sought to identify novel genetic variants that are associated with hs-cTnT levels.
Methods and Results-We performed a genome-wide association in 9491 European Americans and 2053 blacks free of coronary heart disease and heart failure from 2 prospective cohorts: the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Genome-wide association studies were conducted in each study and race stratum. Fixed-effect meta-analyses combined the results of linear regression from 2 cohorts within each race stratum and then across race strata to produce overall estimates and probability values. The meta-analysis identified a significant association at chromosome 8q13 (rs10091374; P=9.06x10(-9)) near the nuclear receptor coactivator 2 (NCOA2) gene. Overexpression of NCOA2 can be detected in myoblasts. An additional analysis using logistic regression and the clinically motivated 99th percentile cut point detected a significant association at 1q32 (rs12564445; P=4.73x10(-8)) in the gene TNNT2, which encodes the cardiac troponin T protein itself. The hs-cTnT-associated single-nucleotide polymorphisms were not associated with coronary heart disease in a large case-control study, but rs12564445 was significantly associated with incident heart failure in Atherosclerosis Risk in Communities Study European Americans (hazard ratio=1.16; P=0.004).
Conclusions-We identified 2 loci, near NCOA2 and in the TNNT2 gene, at which variation was significantly associated with hs-cTnT levels. Further use of the new assay should enable replication of these results. (Circ Cardiovasc Genet. 2013;6:82-88.)
C1 [Yu, Bing; Barbalic, Maja; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Brautbar, Ariel; Nambi, Vijay; Hoogeveen, Ron C.; Ballantyne, Christie M.] Baylor Coll Med, Deptartment Med, Houston, TX 77030 USA.
[Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Tang, Weihong] Univ Minnesota, Deptartment Epidemiol, Minneapolis, MN USA.
[Mosley, Thomas H.] Univ Mississippi, Med Ctr, Div Geriatr, Jackson, MS 39216 USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[deFilippi, Christopher R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[O'Donnell, Christopher J.] NHLBI, Bethesda, MD 20892 USA.
[O'Donnell, Christopher J.] NIH, Framingham Heart Study, Bethesda, MD 20892 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Rice, Ken] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Heckbert, Susan R.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Heckbert, Susan R.] Univ Washington, Dept Epidemiol, 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.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
RP Boerwinkle, E (reprint author), Univ Texas Sch Publ Hlth, Ctr Human Genet, 1200 Herman Pressler E-447, Houston, TX 77030 USA.
EM Eric.Boerwinkle@uth.tmc.edu
FU National Heart, Lung, and Blood Institute [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN2682011000 08C,
HHSN268201100009C, HHSN268201100010C, HHSN2682 01100011C,
HHSN268201100012C, R01HL087641, R01HL59 367, R01HL086694]; National
Human Genome Research Institute [U01HG004402]; National Institutes of
Health [HHSN268200625226C, UL1RR025005]; National Institute on Aging
[AG-023629, AG-15928, AG-20098, AG-027058]; National Center for Research
Resources CTSI [UL 1RR033176]; National Institute of Diabetes and
Digestive and Kidney Diseases [DK063491]; Burroughs Wellcome Fund;
Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)
Consortium; National Heart, Lung, and Blood Institute. [N01-HC-85239,
N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222,
N01-HC-75150, N01-HC-45133, HL080295, HL075366, HL085251, HL087652,
HL105756]
FX 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, HHSN2682011000 08C, HHSN268201100009C,
HHSN268201100010C, HHSN2682 01100011C, and HHSN268201100012C),
R01HL087641, R01HL59 367, 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. This Cardiovascular Health
Study research was supported by the National Heart, Lung, and Blood
Institute contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086;
N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, and
N01-HC-45133,; and National Heart, Lung, and Blood Institute grants
HL080295, HL075366, HL085251, HL087652, and HL105756, with additional
contributions from 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 National Center for Research Resources CTSI grant
UL 1RR033176 and National Institute of Diabetes and Digestive and Kidney
Diseases grant DK063491 to the Southern California Diabetes
Endocrinology Research Center and the Cedars-Sinai Board of Governors'
Chair in Medical Genetics (to Dr Rotter).; We acknowledge the essential
role of The Cohorts for Heart and Aging Research in Genomic Epidemiology
(CHARGE) Consortium in developing and supporting this article. CHARGE
members include the ARIC, the CHS, Framingham Heart Study (FHS) and
Rotterdam Study (RS), and Age, Gene/Environment Susceptibility. The
authors also thank the staff and participants of the ARIC and CHS study
for their important contributions. Dr Yu is supported in part by the
Burroughs Wellcome Fund.
NR 30
TC 8
Z9 8
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD FEB
PY 2013
VL 6
IS 1
BP 82
EP 88
DI 10.1161/CIRCGENETICS.112.963058
PG 7
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 094YL
UT WOS:000315301500013
PM 23247143
ER
PT J
AU Liberti, SE
Larrea, AA
Kunkel, TA
AF Liberti, Sascha E.
Larrea, Andres A.
Kunkel, Thomas A.
TI Exonuclease 1 preferentially repairs mismatches generated by DNA
polymerase alpha
SO DNA REPAIR
LA English
DT Article
DE Exo1; Mismatch repair; Genome stability; Replication fidelity
ID SACCHAROMYCES-CEREVISIAE EXO1; EUKARYOTIC REPLICATION FORK;
ESCHERICHIA-COLI; SYSTEM; YEAST; ERRORS; DELTA; IDENTIFICATION;
RECONSTITUTION; MUTATIONS
AB The Saccharomyces cerevisiae EXO1 gene encodes a 5' exonuclease that participates in mismatch repair (MMR) of DNA replication errors. Deleting EXO1 was previously shown to increase mutation rates to a greater extent when combined with a mutator variant (pol3-L612M) of the lagging strand replicase, DNA polymerase delta (Pol delta), than when combined with a mutator variant (pol2-M644G) of the leading strand replicase, DNA polymerase epsilon (Pol epsilon). Here we confirm that result, and extend the approach to examine the effect of deleting EXO1 in a mutator variant (pol1-L868M) of Pol alpha, the proofreading-deficient and least accurate of the three nuclear replicases that is responsible for initiating Okazaki fragment synthesis. We find that deleting EXO1 increases the mutation rate in the Pol alpha mutator strain to a significantly greater extent than in the Pol delta or Pol epsilon mutator strains, thereby preferentially reducing the efficiency of MMR of replication errors generated by Pol alpha. Because these mismatches are closer to the 5' ends of Okazaki fragments than are mismatches made by Pol delta or Pol epsilon, the results not only support the previous suggestion that Exo1 preferentially excises lagging strand replication errors during mismatch repair, they further imply that the 5' ends serve as entry points for 5' excision of replication errors made by Pol alpha, and possibly as strand discrimination signals for MMR. Nonetheless, mutation rates in the Pol alpha mutator strain are 5- to 25-fold lower in an exo1 Delta strain as compared to an msh2 Delta strain completely lacking MMR, indicating that in the absence of Exo1, most replication errors made by Pol alpha can still be removed in an Msh2-dependent manner by other nucleases and/or by strand displacement. Published by Elsevier B.V.
C1 [Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
FU Division of Intramural Research of the National Institutes of Health,
National Institute of Environmental Health Sciences [Z01 ES065089]
FX We thank Kasia Bebenek and Dmitry Gordenin for thoughtful comments on
the manuscript, and the NIEHS Molecular Genetics Core Facility for
sequencing mutants. This work was supported by Project Z01 ES065089 to
TAK from the Division of Intramural Research of the National Institutes
of Health, National Institute of Environmental Health Sciences.
NR 34
TC 20
Z9 20
U1 0
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD FEB 1
PY 2013
VL 12
IS 2
BP 92
EP 96
DI 10.1016/j.dnarep.2012.11.001
PG 5
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 083TC
UT WOS:000314487100003
PM 23245696
ER
PT J
AU Clausen, AR
Zhang, S
Burgers, PM
Lee, MY
Kunkel, TA
AF Clausen, Anders R.
Zhang, Sufang
Burgers, Peter M.
Lee, Marietta Y.
Kunkel, Thomas A.
TI Ribonucleotide incorporation, proofreading and bypass by human DNA
polymerase delta
SO DNA REPAIR
LA English
DT Article
DE DNA polymerase delta; Ribonucleotide; Incorporation; Proofreading;
Bypass
ID YEAST REPLICATIVE POLYMERASES; EPSILON; REPAIR; INSTABILITY; MUTATIONS
AB In both budding and fission yeast, a large number of ribonucleotides are incorporated into DNA during replication by the major replicative polymerases (Pols alpha, delta and epsilon). They are subsequently removed by RNase H2-dependent repair, which if defective leads to replication stress and genome instability. To extend these studies to humans, where an RNase H2 defect results in an autoimmune disease, here we compare the ability of human and yeast Pol delta to incorporate, proofread, and bypass ribonucleotides during DNA synthesis. In reactions containing nucleotide concentrations estimated to be present in mammalian cells, human Pol delta stably incorporates one rNTP for approximately 2000 dNTPs, a ratio similar to that for yeast Pol delta. This result predicts that human Pol delta may introduce more than a million ribonucleotides into the nuclear genome per replication cycle, an amount recently reported to be present in the genome of RNase H2-defective mouse cells. Consistent with such abundant stable incorporation, we show that the 3'-exonuclease activity of yeast and human Pol delta largely fails to edit ribonucleotides during polymerization. We also show that, like yeast Pol delta, human Pol delta pauses as it bypasses ribonucleotides in DNA templates, with four consecutive ribonucleotides in a DNA template being more problematic than single ribonucleotides. In conjunction with recent studies in yeast and mice, this ribonucleotide incorporation may be relevant to impaired development and disease when RNase H2 is defective in mammals. As one tool to investigate ribonucleotide incorporation by Pol delta in human cells, we show that human Pol delta containing a Leu606Met substitution in the polymerase active site incorporates 7-fold more ribonucleotides into DNA than does wild type Pol delta. Published by Elsevier B.V.
C1 [Clausen, Anders R.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Clausen, Anders R.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Zhang, Sufang; Lee, Marietta Y.] New York Med Coll, Dept Biochem & Mol Biol, Valhalla, NY 10595 USA.
[Burgers, Peter M.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
RI Clausen, Anders R./I-7229-2012;
OI Clausen, Anders Ranegaard/0000-0002-5069-0930
FU [Z01 ES065070]; [GM032431]; [5RO1 GM031973]
FX We thank Roel M. Schaaper and Jessica S. Williams for helpful comments
on the manuscript. This work was supported by Project Z01 ES065070 to
T.A.K., Project GM032431 to P.M.B. and Project 5RO1 GM031973 to M.Y.L.
NR 25
TC 34
Z9 34
U1 1
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD FEB 1
PY 2013
VL 12
IS 2
BP 121
EP 127
DI 10.1016/j.dnarep.2012.11.006
PG 7
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 083TC
UT WOS:000314487100006
PM 23245697
ER
PT J
AU Grisshammer, R
AF Grisshammer, Reinhard
TI Why we need many more G protein-coupled receptor structures
SO EXPERT REVIEW OF PROTEOMICS
LA English
DT Editorial Material
DE crystallization; G protein-coupled receptor; lipidic cubic phase;
neurotensin receptor; structure determination; x-ray
ID RESOLUTION CRYSTAL-STRUCTURE; MEMBRANE-PROTEINS; CRYSTALLIZATION; YIELDS
C1 NINDS, Membrane Prot Struct Funct Unit, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
RP Grisshammer, R (reprint author), NINDS, Membrane Prot Struct Funct Unit, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
EM rkgriss@helix.nih.gov
RI Grisshammer, Reinhard/C-3089-2015
FU Intramural NIH HHS [ZIA NS003016-08]
NR 21
TC 3
Z9 3
U1 1
U2 13
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1478-9450
J9 EXPERT REV PROTEOMIC
JI Expert Rev. Proteomics
PD FEB
PY 2013
VL 10
IS 1
BP 1
EP 3
DI 10.1586/EPR.12.76
PG 3
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 093AB
UT WOS:000315163000001
PM 23414351
ER
PT J
AU Parashar, U
Steele, D
Neuzil, K
De Quadros, C
Tharmaphornpilas, P
Serhan, F
Santosham, M
Patel, M
Glass, R
AF Parashar, Umesh
Steele, Duncan
Neuzil, Kathleen
De Quadros, Ciro
Tharmaphornpilas, Piyanit
Serhan, Fatima
Santosham, Mathu
Patel, Manish
Glass, Roger
TI Progress with rotavirus vaccines: summary of the Tenth International
Rotavirus Symposium
SO EXPERT REVIEW OF VACCINES
LA English
DT Editorial Material
ID REASSORTANT ROTAVIRUS; AFRICAN INFANTS; GASTROENTERITIS; VACCINATION;
CHILDREN; IMMUNOGENICITY; INFECTION; SAFETY; PROTECTION; EFFICACY
AB Over 350 scientific, public and private sector experts from 47 countries convened at the Tenth International Rotavirus Symposium in Bangkok, Thailand on 19-21 September 2012 to discuss progress in the prevention and control of rotavirus, the leading cause of diarrhea hospitalizations and deaths among young children worldwide. Participants discussed data on the burden and epidemiology of rotavirus disease, results of trials of rotavirus vaccines, postmarketing data on vaccine impact and safety from countries that have implemented rotavirus vaccination programs, new insights in rotavirus pathogenesis, immunity and strain diversity, and key issues related to vaccine policy and introduction.
C1 [Parashar, Umesh; Patel, Manish] CDC, Atlanta, GA USA.
[Steele, Duncan] Bill & Melinda Gates Fdn, Seattle, WA USA.
[Neuzil, Kathleen] Program Appl Technol Hlth, Seattle, WA USA.
[De Quadros, Ciro] Sabin Vaccine Inst, Washington, DC USA.
[Tharmaphornpilas, Piyanit] Minist Hlth, Bangkok, Thailand.
[Serhan, Fatima] WHO, CH-1211 Geneva, Switzerland.
[Santosham, Mathu] Johns Hopkins Univ, Baltimore, MD USA.
[Glass, Roger] NIH, Bethesda, MD 20892 USA.
RP Parashar, U (reprint author), CDC, Atlanta, GA USA.
EM uap2@cdc.gov
NR 26
TC 12
Z9 12
U1 0
U2 8
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1476-0584
J9 EXPERT REV VACCINES
JI Expert Rev. Vaccines
PD FEB
PY 2013
VL 12
IS 2
BP 113
EP 117
DI 10.1586/ERV.12.148
PG 5
WC Immunology
SC Immunology
GA 093BS
UT WOS:000315167300009
PM 23414403
ER
PT J
AU Ferreira, JR
Hirsch, ML
Zhang, L
Park, Y
Samulski, RJ
Hu, WS
Ko, CC
AF Ferreira, J. R.
Hirsch, M. L.
Zhang, L.
Park, Y.
Samulski, R. J.
Hu, W-S
Ko, C-C
TI Three-dimensional multipotent progenitor cell aggregates for expansion,
osteogenic differentiation and 'in vivo' tracing with AAV vector
serotype 6
SO GENE THERAPY
LA English
DT Article
DE MAPC; bone formation; adeno-associated virus
ID MESENCHYMAL STEM-CELLS; ADENOASSOCIATED VIRAL VECTORS; RECEPTOR-RELATED
PROTEIN-5; EFFICIENT GENE-TRANSFER; PIG PAROTID-GLANDS; BONE-MARROW;
STROMAL CELLS; BETA-CATENIN; TRANSDUCTION; WNT
AB Multipotent adult progenitor cells (MAPCs) are bone marrow-derived stem cells with a high growth rate suitable for therapeutical applications as three-dimensional (3D) aggregates. Combined applications of osteogenically differentiated MAPC (OD-MAPC) aggregates and adeno-associated viral vectors (AAV) in bone bioengineering are still deferred until information with regard to expansion technologies, osteogenic potential, and AAV cytotoxicity and transduction efficiency is better understood. In this study, we tested whether self-complementary AAV (scAAV) can potentially be used as a gene delivery system in an OD-MAPC-based 'in vivo' bone formation model in the craniofacial region. Both expansion of rat MAPC (rMAPC) and osteogenic differentiation with dexamethasone were also tested in 3D aggregate culture systems 'in vitro' and 'vivo'. rMAPCs grew as undifferentiated aggregates for 4 days, with a population doubling time of 37 h. After expansion, constant levels of Oct4 transcripts, and Oct4 and CD31 surface markers were observed, which constitute a hallmark of undifferentiated stage of rMAPCs. Dexamethasone effectively mediated rMAPC osteogenic differentiation by inducing the formation of a mineralized collagen type I network, and facilitated the activation of the wnt/beta-catenin, a crucial pathway in skeletal development. To investigate the genetic modification of rMAPCs grown as 3D aggregates before implantation, scAAV serotypes 2, 3 and 6 were evaluated. scAAV6 packaged with the enhanced green fluorescent protein expression cassette efficiently mediated long-term transduction (10 days) 'in vitro' and 'vivo'. The reporter transduction event allowed the tracing of OD-rMAPC (induced by dexamethasone) aggregates following OD-rMAPC transfer into a macro-porous hydroxyapatite scaffold implanted in a rat calvaria model. Furthermore, the scAAV6-transduced OD-rMAPCs generated a bone-like matrix with a collagenous matrix rich in bone-specific proteins (osteocalcin and osteopontin) in the scaffold macro-pores 10 days post-implantation. Newly formed bone was also observed in the interface between native bone and scaffold. The collective work supports future bone tissue engineering applications of 3D MAPC cultures for expansion, bone formation and the ability to alter genetically these cells using scAAV vectors. Gene Therapy (2013) 20, 158-168; doi:10.1038/gt.2012.16; published online 8 March 2012
C1 [Ferreira, J. R.; Ko, C-C] Univ N Carolina, Sch Dent, Chapel Hill, NC USA.
[Ferreira, J. R.] NIDCR, Matrix & Morphogenesis Sect, Bethesda, MD 20892 USA.
[Hirsch, M. L.; Samulski, R. J.] Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC USA.
[Zhang, L.] Capital Med Univ, Fac Stomatol, Beijing, Peoples R China.
[Park, Y.] Catholic Univ Louvain, Interdept Stem Cell Inst, B-3000 Louvain, Belgium.
[Hu, W-S] Univ Minnesota, Minneapolis, MN USA.
[Ko, C-C] N Carolina State Univ, Raleigh, NC 27695 USA.
RP Ferreira, JR (reprint author), NIDCR, Matrix & Morphogenesis Sect, LCDB, NIH, 30 Convent Dr,Room 429, Bethesda, MD 20892 USA.
EM andraderequicj@nidcr.nih.gov
RI Ferreira, Joao/M-1517-2016; Ferreira, Joao/G-4015-2013
OI Ferreira, Joao/0000-0002-4230-4593; Ferreira, Joao/0000-0002-2411-6273
FU FCT-Portuguese Foundation for Science and Technology
[SFRH/BD/36841/2007]; NIH/NIDCR [K08DE018695]; NC Biotech Center,
American Association for Orthodontist Foundation; Northwest Genome
Engineering Consortium; Wellstone [5U54AR056953]; NH [5R01Al072176]
FX We thank Sandra Horton at North Carolina State University for processing
'in vivo' tissue specimens for immunohistochemistry and Victoria Madden
at UNC Microscopy Services Laboratory for processing in vitro cell
matrices for electron microscopy. Also, we would like to acknowledge Dr
Ganokon Urkasemsin for her contribution towards the statistical analysis
of this project. Joao Ferreira was supported by the doctoral fellowship
of FCT-Portuguese Foundation for Science and Technology
(SFRH/BD/36841/2007). This work was supported in part by grants from
the: NIH/NIDCR (K08DE018695), NC Biotech Center, American Association
for Orthodontist Foundation awarded to C-CK; Northwest Genome
Engineering Consortium pilot awarded to MLH; and Wellstone
(5U54AR056953) and NH (5R01Al072176) awarded to RJS.
NR 47
TC 4
Z9 4
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0969-7128
J9 GENE THER
JI Gene Ther.
PD FEB
PY 2013
VL 20
IS 2
BP 158
EP 168
DI 10.1038/gt.2012.16
PG 11
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Research & Experimental Medicine
GA 091UD
UT WOS:000315074400007
PM 22402320
ER
PT J
AU Aloia, AL
Duffy, L
Pak, V
Lee, KE
Sanchez-Martinez, S
Derse, D
Heidecker, G
Cornetta, K
Rein, A
AF Aloia, A. L.
Duffy, L.
Pak, V.
Lee, K. E.
Sanchez-Martinez, S.
Derse, D.
Heidecker, G.
Cornetta, K.
Rein, A.
TI A reporter system for replication-competent gammaretroviruses: the
inGluc-MLV-DERSE assay
SO GENE THERAPY
LA English
DT Article
DE replication-competent gannmaretrovirus; gene-therapy vectors;
infectivity assay
ID PACKAGING CELL-LINE; RECOMBINATION EVENTS; GAUSSIA LUCIFERASE; INDICATOR
GENE; RETROVIRUS; VIRUS; CULTURE; VECTOR; RETROTRANSPOSITION; EXPRESSION
AB Although novel retroviral vectors for use in gene-therapy products are reducing the potential for formation of replication-competent retrovirus (RCR), it remains crucial to screen products for RCR for both research and clinical purposes. For clinical-grade gammaretrovirus-based vectors, RCR screening is achieved by an extended S+L- or marker-rescue assay, whereas standard methods for replication-competent lentivirus detection are still in development. In this report, we describe a rapid and sensitive method for replication-competent gammaretrovirus detection. We used this assay to detect three members of the gammaretrovirus family and compared the sensitivity of our assay with well-established methods for retrovirus detection, including the extended S(+)1(-) assay. Results presented here demonstrate that this assay should be useful for gene-therapy product testing. Gene Therapy (2013) 20, 169-176; doi:10.1038/gt.2012.18; published online 8 March 2012
C1 [Aloia, A. L.; Pak, V.; Lee, K. E.; Sanchez-Martinez, S.; Derse, D.; Heidecker, G.; Rein, A.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Duffy, L.; Cornetta, K.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA.
[Cornetta, K.] Indiana Univ Sch Med, Dept Med, Indianapolis, IN USA.
[Cornetta, K.] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN USA.
RP Rein, A (reprint author), NCI, HIV Drug Resistance Program, 1050 Boyles St,Bldg 535,Room 211, Frederick, MD 21702 USA.
EM reina@mail.nih.gov
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research; National Center for Research Resource
(National Gene Vector Biorepository) [P40 RR024928]
FX We thank Jane Mirro, Gerry Princler, Patricia Lloyd and Shawn Hill for
superb technical assistance, and Vineet KewalRamani for many helpful
discussions. This work was supported in part by the Intramural Research
Program of the NIH, National Cancer Institute and Center for Cancer
Research. Work at Indiana University is supported by the NIH, National
Center for Research Resource (National Gene Vector Biorepository P40
RR024928).
NR 29
TC 2
Z9 2
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0969-7128
J9 GENE THER
JI Gene Ther.
PD FEB
PY 2013
VL 20
IS 2
BP 169
EP 176
DI 10.1038/gt.2012.18
PG 8
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Research & Experimental Medicine
GA 091UD
UT WOS:000315074400008
PM 22402321
ER
PT J
AU Sommers, R
Goold, SD
McGlynn, EA
Pearson, SD
Danis, M
AF Sommers, Roseanna
Goold, Susan Dorr
McGlynn, Elizabeth A.
Pearson, Steven D.
Danis, Marion
TI Focus Groups Highlight That Many Patients Object To Clinicians' Focusing
On Costs
SO HEALTH AFFAIRS
LA English
DT Article
ID HEALTH-CARE; PHYSICIANS; DECISIONS
AB Having patients weigh costs when making medical decisions has been proposed as a way to rein in health care spending. We convened twenty-two focus groups of people with insurance to examine their willingness to discuss health care costs with clinicians and consider costs when deciding among nearly comparable clinical options. We identified the following four barriers to patients' taking cost into account: a preference for what they perceive as the best care, regardless of expense; inexperience with making trade-offs between health and money; a lack of interest in costs borne by insurers and society as a whole; and noncooperative behavior characteristic of a "commons dilemma," in which people act in their own self-interest although they recognize that by doing so, they are depleting limited resources. Surmounting these barriers will require new research in patient education, comprehensive efforts to shift public attitudes about health care costs, and training to prepare clinicians to discuss costs with their patients.
C1 [Sommers, Roseanna] Yale Univ, Sch Law, New Haven, CT 06520 USA.
[Goold, Susan Dorr] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Goold, Susan Dorr] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
[McGlynn, Elizabeth A.] Kaiser Permanente Ctr Effectiveness & Safety Res, Oakland, CA USA.
[Pearson, Steven D.] Massachusetts Gen Hosp, Inst Clin & Econ Review, Boston, MA 02114 USA.
[Danis, Marion] NIH, Sect Eth & Hlth Policy, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
[Danis, Marion] NIH, Eth Consultat Serv, Ctr Clin, Bethesda, MD 20892 USA.
RP Sommers, R (reprint author), Yale Univ, Sch Law, New Haven, CT 06520 USA.
EM mdanis@nih.gov
OI Goold, Susan Dorr/0000-0002-0258-9774
FU Office of the Director; Department of Bioethics at the National
Institutes of Health
FX An earlier version of this article was presented at the 2012 annual
meeting of the American Society for Bioethics and Humanities,
Washington, D. C., October 21, 2012. This project was funded by the
Office of the Director and the Department of Bioethics at the National
Institutes of Health. The authors thank Beverly Weidmer, Shirley Chen,
Jean Logan, and Greer Donley for assistance with the survey design, data
collection, and data coding. The views expressed here are those of the
authors and do not necessarily reflect the policies of the American
Medical Association, the National Institutes of Health, or the
Department of Health and Human Services.
NR 23
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U1 0
U2 13
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD FEB
PY 2013
VL 32
IS 2
BP 338
EP 346
DI 10.1377/hlthaff.2012.0686
PG 9
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 093QQ
UT WOS:000315206900019
PM 23381527
ER
PT J
AU Danis, M
Solomon, M
AF Danis, Marion
Solomon, Mildred
TI Providers, Payers, The Community, And Patients Are All Obliged To Get
Patient Activation And Engagement Ethically Right
SO HEALTH AFFAIRS
LA English
DT Article
ID HEALTH-PROMOTION; MANAGEMENT; PROGRAM; OUTCOMES; CARE
AB Active and engaged patients seek the understanding, knowledge, and skills to promote their own health. Efforts to promote such patient activation and engagement are ethically justified because they are consonant with the well-established principle of respect for persons and, as the evidence shows, because they are likely to produce better outcomes for patients. Yet patient activation and engagement can also go ethically awry if, for example, nonadherent patients are abandoned or are unduly disadvantaged by punitive policies and practices, or if the conditions for successful activation and engagement are missing. In this article we discuss the ethical issues and responsibilities that pertain to patients, clinicians, health care organizations, delivery systems, insurers, payers, and communities. For example, physicians or payers could hold patients blameworthy for not following recommendations, but we suggest that a better approach would be for providers and payers to empower patients to effectively share responsibility for defining goals and achieving them. An ethical approach to patient activation and engagement should place obligations not only on patients but also on clinicians, health care organizations and delivery systems, insurers, and communities.
C1 [Danis, Marion] NIH, Sect Eth & Hlth Policy, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
[Solomon, Mildred] Hastings Ctr, Garrison, NY USA.
RP Danis, M (reprint author), NIH, Sect Eth & Hlth Policy, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM mdanis@nih.gov
FU National Institutes of Health
FX This work was funded in part by the intramural program of the National
Institutes of Health. The authors thank Steve Pearson, Amina White,
Peter Lichstein, and Elizabeth Gamble for their advice during the
preparation of this article. The views expressed here are those of the
authors and not necessarily a reflection of policies of the Department
of Health and Human Services or the National Institutes of Health.
NR 29
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Z9 5
U1 0
U2 8
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD FEB
PY 2013
VL 32
IS 2
BP 401
EP 407
DI 10.1377/hlthaff.2012.1081
PG 7
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 093QQ
UT WOS:000315206900026
PM 23381534
ER
PT J
AU Popovic-Kuzmanovic, D
Novakovic, I
Stojanovich, L
Aksentijevich, I
Zogovic, N
Tovilovic, G
Trajkovic, V
AF Popovic-Kuzmanovic, Dragana
Novakovic, Ivana
Stojanovich, Ljudmila
Aksentijevich, Ivona
Zogovic, Nevena
Tovilovic, Gordana
Trajkovic, Vladimir
TI Increased activity of interleukin-23/interleukin-17 cytokine axis in
primary antiphospholipid syndrome
SO IMMUNOBIOLOGY
LA English
DT Article
DE Antiphospholipid syndrome; IL-17; IL-23; TGF-beta; Gene polymorphism
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; INFLAMMATORY-BOWEL-DISEASE; FACTOR-ALPHA
LEVELS; REGULATORY T-CELLS; MULTIPLE-SCLEROSIS; TGF-BETA;
RHEUMATOID-ARTHRITIS; GROWTH-FACTOR; SYNDROME APS; IN-VIVO
AB The aim of the study was to investigate serum concentrations of interleukin (IL)-17 and IL-17-inducing cytokines IL-23 and transforming growth factor (TGF)-beta, as well as IL-17 single nucleotide polymorphism (SNP) rs2275913 in patients with primary antiphospholipid syndrome (PAPS). We studied fifty patients with PAPS and fifty age- and sex-matched healthy controls. The cytokine levels were measured by ELISA, while the rs2275913 SNP located in promoter region of IL-17 gene was genotyped using real-time PCR. The significantly higher levels of IL-17 (p = 0.002), IL-23 (p < 0.001) and TGF-beta (p = 0.042) were found in PAPS patients (median 13.1, 9.4, and 125.6 pg/ml, respectively) compared to the control group (6.8, 4.9 and 44.4 pg/ml). There was a significant positive correlation between concentrations of IL-17 and IL-23 (r = 0.540, p < 0.001), but not between those of IL-17 and TGF-beta. No statistically significant differences were observed in the distribution of genotypes and alleles of the IL-17 rs2275913 variants in patients with PAPS compared to healthy subjects. The blood concentrations of IL-17 did not differ in subjects with different rs2275913 genotypes or patients with or without antiphospholipid antibodies. Finally, a trend toward higher IL-17 levels (p = 0.063) and the significantly higher IL-17 concentrations (p = 0.012) were observed in PAPS patients with deep vein thrombosis and thrombocytopenia, respectively. These data demonstrate that IL-23/IL-17 axis, stimulated independently of TGF-beta increase IL-17A gene polymorphism and antiphospholipid antibody production, might contribute to vascular manifestations of PAPS. (C) 2012 Elsevier GmbH. All rights reserved.
C1 [Popovic-Kuzmanovic, Dragana; Stojanovich, Ljudmila] Univ Belgrade, Med Ctr Bezanijska Kosa, Belgrade, Serbia.
[Novakovic, Ivana] Univ Belgrade, Sch Med, Inst Biol, Belgrade, Serbia.
[Aksentijevich, Ivona] NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA.
[Zogovic, Nevena; Tovilovic, Gordana] Univ Belgrade, Inst Biol Res, Belgrade, Serbia.
[Trajkovic, Vladimir] Univ Belgrade, Sch Med, Inst Microbiol & Immunol, Belgrade 11000, Serbia.
RP Trajkovic, V (reprint author), Univ Belgrade, Sch Med, Inst Microbiol & Immunol, Belgrade 11000, Serbia.
EM vtrajkovic@med.bg.ac.rs
OI Tovilovic-Kovacevic, Gordana/0000-0001-6150-3996; Zogovic,
Nevena/0000-0003-4240-3193
FU Ministry of Education and Science of the Republic of Serbia [41025,
175091]
FX The study was supported by the Ministry of Education and Science of the
Republic of Serbia (Grant Number 41025 and 175091).
NR 56
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U1 0
U2 8
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 0171-2985
J9 IMMUNOBIOLOGY
JI Immunobiology
PD FEB
PY 2013
VL 218
IS 2
BP 186
EP 191
DI 10.1016/j.imbio.2012.03.002
PG 6
WC Immunology
SC Immunology
GA 095CJ
UT WOS:000315312000008
PM 22559912
ER
PT J
AU Greenaway, HY
Ng, B
Price, DA
Douek, DC
Davenport, MP
Venturi, V
AF Greenaway, Hui Yee
Ng, Benedict
Price, David A.
Douek, Daniel C.
Davenport, Miles P.
Venturi, Vanessa
TI NKT and MAIT invariant TCR alpha sequences can be produced efficiently
by VJ gene recombination
SO IMMUNOBIOLOGY
LA English
DT Article
DE Invariant T cell receptor; MAIT cell; NKT cell; Public T cell response;
T cell receptor; T cell repertoire
ID T-CELL-RECEPTOR; ANTIGEN RECEPTOR; GENOME SEQUENCE; CONVERGENT
RECOMBINATION; MULTIPLE-SCLEROSIS; PERIPHERAL-BLOOD; CDR3 REGION; CHAIN;
RECOGNITION; REPERTOIRE
AB Semi-invariant T cell receptors (TCRs) found on natural killer T (NKT) and mucosal-associated invariant T (MAIT) cells are characterized by the use of invariant variable (V) and joining (J) gene combinations in the TCR alpha-chain, as well as ubiquitous canonical TCR alpha amino acid sequences that are dominant in many individuals and similar across species. That they are so prevalent indicates that they occupy an important niche within the immune system. However, these TCRs are produced by a largely random gene recombination process, which seems a risky approach for the immune system to acquire these innate-like cells. We surveyed studies reporting NKT and MAIT TCR alpha sequences for six and four different species, respectively. Although the germline nature of the canonical human and mouse NKT and mouse MAIT TCR alpha sequences and an overlap of nucleotides between the mouse MAIT-related V alpha and J alpha genes have been noted in previous studies, in this study we demonstrate that, for all reported species, the canonical TCR amino acid sequences can be encoded by at least one germline-derived nucleotide sequence. Moreover, these nucleotide sequences can utilize an overlap between the V alpha and J alpha genes in their production, which enables them to be produced by a large variety of recombination mechanisms. We investigated the role of these TCR alpha features in the production of the canonical NKT and MAIT TCRa sequences. In computer simulations of a random recombination process involving the invariant NKT and MAIT TCR alpha gene combinations for each species, the canonical NKT and MAIT TCR alpha sequences were the first or second most generated of all sequences with the CDR3 alpha length restrictions associated with NKT and MAIT cells. These results suggest that the immune machinery enables the canonical NKT and MAIT TCR alpha sequences to be produced with great efficiency through the Process of convergent recombination, ensuring their prevalence across individuals and species. (C) 2012 Elsevier GmbH. All rights reserved.
C1 [Greenaway, Hui Yee; Ng, Benedict; Venturi, Vanessa] Univ New S Wales, Ctr Vasc Res, Computat Biol Grp, Kensington, NSW 2052, Australia.
[Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff, S Glam, Wales.
[Price, David A.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Davenport, Miles P.] Univ New S Wales, Ctr Vasc Res, Complex Syst Biol Grp, Kensington, NSW 2052, Australia.
RP Davenport, MP (reprint author), Univ New S Wales, Ctr Vasc Res, Kensington, NSW 2052, Australia.
EM m.davenport@unsw.edu.au; v.venturi@unsw.edu.au
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
FU Australian Research Council (ARC); Australian National Health and
Medical Research Council (NHMRC); Australian Postgraduate Award
FX This work was supported by the Australian Research Council (ARC) and
Australian National Health and Medical Research Council (NHMRC). HYG is
supported by an Australian Postgraduate Award, DAP is a Medical Research
Council (UK) Senior Clinical Fellow, MPD is an NHMRC Senior Research
Fellow and VV is an ARC Future Fellow.
NR 81
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U1 2
U2 11
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 0171-2985
J9 IMMUNOBIOLOGY
JI Immunobiology
PD FEB
PY 2013
VL 218
IS 2
BP 213
EP 224
DI 10.1016/j.imbio.2012.04.003
PG 12
WC Immunology
SC Immunology
GA 095CJ
UT WOS:000315312000011
PM 22647874
ER
PT J
AU Banegas, MP
Yabroff, KR
AF Banegas, Matthew P.
Yabroff, K. Robin
TI Out of Pocket, Out of Sight? An Unmeasured Component of the Burden of
Cancer
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID UNITED-STATES; DRUGS; CARE; COST
C1 [Banegas, Matthew P.; Yabroff, K. Robin] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
RP Banegas, MP (reprint author), NCI, Hlth Serv & Econ Branch Appl Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,Rm 4019, Bethesda, MD 20892 USA.
EM banegasmp@mail.nih.gov
OI Yabroff, K. Robin/0000-0003-0644-5572
NR 18
TC 5
Z9 5
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD FEB
PY 2013
VL 105
IS 4
BP 252
EP 254
DI 10.1093/jnci/djs641
PG 4
WC Oncology
SC Oncology
GA 093PD
UT WOS:000315202900004
PM 23349251
ER
PT J
AU Burns, KM
Evans, F
Pearson, GD
Berul, CI
Kaltman, JR
AF Burns, Kristin M.
Evans, Frank
Pearson, Gail D.
Berul, Charles I.
Kaltman, Jonathan R.
TI Rising Charges and Costs for Pediatric Catheter Ablation
SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY
LA English
DT Article
DE catheter ablation; congenital heart defects; epidemiology; health care
costs; pediatrics
ID CONGENITAL HEART-DISEASE; HEALTH-CARE COSTS; SUPRAVENTRICULAR
TACHYCARDIA; RADIOFREQUENCY ABLATION; HOSPITAL CHARGES; INTENSIVE-CARE;
YOUNG-ADULTS; CHILDREN; OUTCOMES; INFANTS
AB Pediatric Ablation Charges and Costs Are Rising.Introduction: Catheter ablation has been shown to be effective for pediatric tachyarrhythmias, but the associated charges and costs have not been described in the recent era. Understanding such contemporary trends may identify ways to keep an effective therapy affordable while optimizing clinical outcomes. Methods: We used the 19972009 Kids' Inpatient Databases to examine trends in charges and costs for pediatric catheter ablation and identify determinants of temporal changes. Results: There were 7,130 discharges for catheter ablation in the sample. Mean age at ablation was 12.1 +/- 0.2 years. Patients with congenital heart disease (CHD) made up 10% of the sample. Complications occurred in 8% of discharges. Mean total charges rose 219% above inflation (from $23,798 +/- 1,072 in 1997 to $75,831 +/- 2,065 in 2009). From 2003 to 2009, costs rose 25% (from $20,459 +/- 780 in 2003 to $25,628 +/- 992 in 2009). Charges for ablation increased markedly relative to surgical procedures, but with a similar slope to other catheter-based interventions. Multivariable analysis revealed that year (P < 0.0001), payer (P = 0.0002), CHD (P < 0.0001), valvular heart disease (P = 0.0004), cardiomyopathy (P = 0.0009), hospital region (P < 0.0001), length of stay (P < 0.0001), and complications (P < 0.0001) predicted increased charges. The same factors also predicted increased costs. Charges and costs varied considerably by region, particularly for high-volume centers (P < 0.0001). Conclusions: Charges and costs for pediatric catheter ablation increased relative to other procedures and significantly outstripped inflation. Further study of complications, length of stay, and regional differences may help control rising costs while maintaining quality of care. (J Cardiovasc Electrophysiol, Vol. 24, pp. 162-169, February 2013)
C1 [Burns, Kristin M.; Evans, Frank; Pearson, Gail D.; Kaltman, Jonathan R.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Burns, Kristin M.; Pearson, Gail D.; Berul, Charles I.; Kaltman, Jonathan R.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
RP Burns, KM (reprint author), NHLBI, Heart Dev & Struct Dis Branch, Div Cardiovasc Sci, NIH, 6701 Rockledge Dr,Room 8107, Bethesda, MD 20892 USA.
EM kristin.burns@nih.gov
NR 32
TC 3
Z9 3
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1045-3873
EI 1540-8167
J9 J CARDIOVASC ELECTR
JI J. Cardiovasc. Electrophysiol.
PD FEB
PY 2013
VL 24
IS 2
BP 162
EP 169
DI 10.1111/j.1540-8167.2012.02446.x
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 083NF
UT WOS:000314470500011
PM 23066833
ER
PT J
AU Okur, A
Miller, BT
Joo, K
Lee, J
Brooks, BR
AF Okur, Asim
Miller, Benjamin T.
Joo, Keehyoung
Lee, Jooyoung
Brooks, Bernard R.
TI Generating Reservoir Conformations for Replica Exchange through the Use
of the Conformational Space Annealing Method
SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION
LA English
DT Article
ID MOLECULAR-DYNAMICS SIMULATIONS; TRP-CAGE MINIPROTEIN; PROTEIN-STRUCTURE
PREDICTION; FREE-ENERGY LANDSCAPE; CIS PEPTIDE-BONDS; EXPLICIT SOLVENT;
FOLDING SIMULATIONS; MINI-PROTEIN; BETA-HAIRPIN; WATER
AB Temperature replica exchange molecular dynamics (T-REM) has been successfully used to improve the conformational search for model peptides and small proteins. However, for larger and more complicated systems, the use of T-REM is computationally intensive since the complexity of the free energy landscape and number of required replicas increase with system size. Achieving convergence of systems with slow transition kinetics is often difficult. Several methods have been proposed to overcome the size and convergence speed issues of standard T-REM. One of these is the Reservoir Replica Exchange Method (R-REM), in which the conformational search and temperature equilibration are separated by exchanging with a pre-existing reservoir of structures. This approach allows the integration of computationally efficient search algorithms with replica exchange. The Conformational Space Annealing (CSA) method has been shown to be able to determine the global energy minimum of proteins efficiently and has been used in structure prediction successfully. CSA uses a genetic algorithm to generate a diverse set of conformations to determine the minimum energy structure. We combine these methods by using conformations generated by the CSA method to build a reservoir. R-REM is then used to seed the top replica with the structures from the reservoir; fast convergence at every temperature is observed. The efficiency of this method is then demonstrated with model peptides and small proteins, and significant improvement of efficiency is observed while maintaining the overall shape of the free energy landscape.
C1 [Okur, Asim; Miller, Benjamin T.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
[Joo, Keehyoung; Lee, Jooyoung] Korea Inst Adv Study, Sch Computat Sci, Seoul, South Korea.
[Joo, Keehyoung; Lee, Jooyoung] Korea Inst Adv Study, Ctr Adv Computat, Seoul, South Korea.
RP Okur, A (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM okura@mail.nih.gov
OI Miller, Benjamin/0000-0003-1647-0122
FU Intramural Research Program of the NIH; NHLBI; National Research
Foundation of Korea (NRF); Korea government (MEST) [20120001222]
FX This research was supported by the Intramural Research Program of the
NIH, NHLBI, and utilized the high-performance computational capabilities
of the LoBoS (www.lobos.nih.gov) computer cluster. K.J. and J.L. are
supported by the National Research Foundation of Korea (NRF) grant
funded by the Korea government (MEST; No. 20120001222). We also would
like to thank Rich Pastor and Michael Shirts for useful discussions.
NR 50
TC 3
Z9 3
U1 2
U2 20
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9618
J9 J CHEM THEORY COMPUT
JI J. Chem. Theory Comput.
PD FEB
PY 2013
VL 9
IS 2
BP 1115
EP 1124
DI 10.1021/ct300996m
PG 10
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 090ZK
UT WOS:000315018300029
PM 23585739
ER
PT J
AU Craig, MT
Mayne, EW
Bettler, B
Paulsen, O
McBain, CJ
AF Craig, Michael T.
Mayne, Elizabeth W.
Bettler, Bernhard
Paulsen, Ole
McBain, Chris J.
TI Distinct roles of GABAB1a- and GABAB1b-containing GABAB receptors in
spontaneous and evoked termination of persistent cortical activity
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Article
ID SLOW OSCILLATION; INHIBITORY INTERNEURONS; NEOCORTICAL NEURONS;
PYRAMIDAL NEURONS; NETWORK ACTIVITY; CELLULAR BASIS; IN-VIVO; LAYER-I;
SLEEP; RAT
AB During slow-wave sleep, cortical neurons display synchronous fluctuations between periods of persistent activity (UP states') and periods of relative quiescence (DOWN states'). Such UP and DOWN states are also seen in isolated cortical slices. Recently, we reported that both spontaneous and evoked termination of UP states in slices from the rat medial entorhinal cortex (mEC) involves GABAB receptors. Here, in order to dissociate the roles of GABAB1a- and GABAB1b-containing receptors in terminating UP states, we used mEC slices from mice in which either the GABAB1a or the GABAB1b subunit had been genetically ablated. Pharmacological blockade of GABAB receptors using the antagonist CGP55845 prolonged the UP state duration in both wild-type mice and those lacking the GABAB1b subunit, but not in those lacking the GABAB1a subunit. Conversely, electrical stimulation of layer 1 could terminate an ongoing UP state in both wild-type mice and those lacking the GABAB1a subunit, but not in those lacking the GABAB1b subunit. Together with previous reports, indicating a preferential presynaptic location of GABAB1a- and postsynaptic location of GABAB1b-containing receptors, these results suggest that presynaptic GABAB receptors contribute to spontaneous DOWN state transitions, whilst postsynaptic GABAB receptors are essential for the afferent termination of the UP state. Inputs to layer 1 from other brain regions could thus provide a powerful mechanism for synchronizing DOWN state transitions across cortical areas via activation of GABAergic interneurons targeting postsynaptic GABAB receptors.
C1 [Craig, Michael T.; Mayne, Elizabeth W.; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD 20892 USA.
[Craig, Michael T.; Mayne, Elizabeth W.; Paulsen, Ole] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England.
[Bettler, Bernhard] Univ Basel, Inst Physiol, Dept Biomed, CH-4056 Basel, Switzerland.
[Paulsen, Ole] Univ Cambridge, Physiol Lab, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England.
RP McBain, CJ (reprint author), NICHD, LCSN, Sect Cellular & Synapt Neurophysiol, Porter Neurosci Ctr, Bldg 35,Rm 3C903,35 Lincoln Dr, Bethesda, MD 20892 USA.
EM op210@cam.ac.uk; mcbainc@mail.nih.gov
RI Craig, Michael/E-7070-2011
OI Craig, Michael/0000-0001-8481-6709
FU Wellcome Trust OXION initiative; National Institute of Child Health and
Human Development (NICHD) intramural award; Wellcome Trust; British
Embassy Science and Innovation Division; NIHMD/PhD Partnership Training
programme; Rhodes Trust
FX This work was supported by the Wellcome Trust OXION initiative (M. T.
C., O.P.) and a National Institute of Child Health and Human Development
(NICHD) intramural award (C.J.M.). M. T. C. held a Wellcome Trust Prize
Studentship, received travel funding from the British Embassy Science
and Innovation Division, and is an NIH Visiting Fellow. E. W. M. is
supported by the NIHMD/PhD Partnership Training programme and by the
Rhodes Trust. We are grateful to Olivia Shipton for useful discussions
and help with animal breeding.
NR 35
TC 15
Z9 15
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3751
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD FEB
PY 2013
VL 591
IS 4
BP 835
EP 843
DI 10.1113/jphysiol.2012.248088
PG 9
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 092VB
UT WOS:000315150000011
PM 23266934
ER
PT J
AU Berger, VW
AF Berger, Vance W.
TI ON THE INSUFFICIENCY OF REPORTING MASKING
SO JOURNAL OF REHABILITATION MEDICINE
LA English
DT Letter
C1 [Berger, Vance W.] NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
[Berger, Vance W.] UMBC, Bethesda, MD 20892 USA.
RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA.
EM vb78c@nih.gov
NR 0
TC 3
Z9 3
U1 0
U2 0
PU FOUNDATION REHABILITATION INFORMATION
PI UPPSALA
PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN
SN 1650-1977
J9 J REHABIL MED
JI J. Rehabil. Med.
PD FEB
PY 2013
VL 45
IS 2
BP 221
EP 221
DI 10.2340/16501977-1108
PG 1
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 093GM
UT WOS:000315179700019
PM 23303555
ER
PT J
AU Stewart, R
Weyant, RJ
Garcia, ME
Harris, T
Launer, LJ
Satterfield, S
Sirnonsick, EM
Yaffe, K
Newman, AB
AF Stewart, Robert
Weyant, Robert J.
Garcia, Melissa E.
Harris, Tamara
Launer, Lenore J.
Satterfield, Suzanne
Sirnonsick, Eleanor M.
Yaffe, Kristine
Newman, Anne B.
TI Adverse Oral Health and Cognitive Decline: The Health, Aging and Body
Composition Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE cognitive decline; cognitive impairment; periodontitis; periodontal
disease; gingivitis
ID ATHEROSCLEROTIC VASCULAR-DISEASE; PERIODONTAL-DISEASE; INFLAMMATORY
MARKERS; ALZHEIMERS-DISEASE; CASE DEFINITIONS; DENTAL-HEALTH; TOOTH
LOSS; POPULATION; DEMENTIA; RISK
AB OBJECTIVES: To investigate the relationship between periodontal disease and cognitive decline. DESIGN: Analysis of a prospective cohort study.
SETTING: The Health, Aging and Body Composition (Health ABC) Study.
PARTICIPANTS: One thousand fifty-three participants who were administered the Modified Mini-Mental State Examination (3MS) at Year 1 (baseline) and Year 3 and had participated in a comprehensive periodontal examination at Year 2.
MEASUREMENTS: The prospective association between a range of oral health parameters and cognitive function was examined. Decline in 3MS score from Year 3 to 5 was investigated in 947 (89.9%) participants. Covariates included age, sex, education, race, cardiovascular disease and risk, and depressive symptoms.
RESULTS: Most indicators of adverse oral health at Year 2 were associated with cognitive impairment based on averaged 3MS scores less than 80 for Years 1 and 3, but education and race substantially confounded these associations. Higher gingival index, a measure of gingival inflammation, at Year 2 remained independently associated with this definition of cognitive impairment and, in fully adjusted analyses, was also an independent predictor of a more-than-5-point cognitive decline from Year 3 to S.
CONCLUSION: Periodontitis may be a risk factor for cognitive decline. Gingivitis is reversible, and periodontitis to some degree is preventable and controllable when manifest. Therefore, further research is needed to clarify potential underlying mechanisms and oral health interventions that might ameliorate cognitive decline. J Am Geriatr Soc 61:177-184, 2013.
C1 [Stewart, Robert] Kings Coll London, London Inst Psychiat, London WC2R 2LS, England.
[Weyant, Robert J.] Univ Pittsburgh, Sch Dent Med, Dept Dent Publ Hlth, Pittsburgh, PA USA.
[Garcia, Melissa E.; Harris, Tamara; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Knoxville, TN USA.
[Sirnonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Aging & Populat Hlth, Pittsburgh, PA USA.
RP Stewart, R (reprint author), Inst Psychiat, Epidemiol Sect, Box 60,De Crespigny Pk, London SE5 8AF, England.
EM r.stewart@iop.kcl.ac.uk
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Stewart, Robert/0000-0002-4435-6397
FU Wellcome Trust; National Institute for Health Research (NIHR) Biomedical
Research Centre; Dementia Biomedical Research Unit at South London;
Maudsley NHS Foundation Trust; King's College London; Pfizer; Eisai;
Lunbeck; JJ; Roche; National Institute for Drug Abuse; National
Institute for Dental and Craniofacial Research; Health Resources and
Services Administration; University of Padua; University of Verona;
Imperial College London; U.S. Public Health Service [N01-AG-6-2103,
1R01AG028050, N01-AG-6-2106]; NIH
FX Robert Stewart has received research funding in the last 2 years from
the Wellcome Trust and from the National Institute for Health Research
(NIHR) Biomedical Research Centre and Dementia Biomedical Research Unit
at South London and Maudsley NHS Foundation Trust and King's College
London, and has received research support, travel support, and honoraria
from Pfizer, Eisai, Lunbeck, J&J, and Roche. Robert Weyant receives an
honorarium as Editor-in-Chief of the Journal of Public Health Dentistry
and has received research funding from the National Institute for Drug
Abuse, the National Institute for Dental and Craniofacial Research, and
the Health Resources and Services Administration. Tamara Harris is a
U.S. government employee and declares that all funding sources have been
from U.S. federal government and academic centers, that travel support
has been received from University of Padua, University of Verona, and
Imperial College London, spouse consultancy fees from Imperial College
London and children's stock holding in Web MD. Suzanne Satterfield
declares that the Memphis Clinical Site for Health ABC received support
from U.S. Public Health Service Contracts N01-AG-6-2103, 1R01AG028050,
and N01-AG-6-2106. Eleanor M. Simonsick is a full-time employee of the
U.S. federal government with all funding from NIH and has no financial
relationships to declare. Kristine Yaffe has served as a consultant to
Novartis and serves on data and safety monitoring boards for the
National Institute of Mental Health, Pfizer, and Medivation as well as
the National Institute on Aging/Beeson Scientific Advisory Committee.
Anne B. Newman has a consultancy with Merck in 2008.
NR 45
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Z9 18
U1 2
U2 29
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD FEB
PY 2013
VL 61
IS 2
BP 177
EP 184
DI 10.1111/jgs.12094
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 094HY
UT WOS:000315254800001
PM 23405916
ER
PT J
AU Chang, M
Saczynski, JS
Snaedal, J
Bjornsson, S
Einarsson, B
Garcia, M
Aspelund, T
Siggeirsdottir, K
Gudnason, V
Launer, LJ
Harris, TB
Jonsson, PV
AF Chang, Milan
Saczynski, Jane S.
Snaedal, Jon
Bjornsson, Sigurbjorn
Einarsson, Bjorn
Garcia, Melissa
Aspelund, Thor
Siggeirsdottir, Kristine
Gudnason, Vilrnundur
Launer, Lenore J.
Harris, Tamara B.
Jonsson, Palmi V.
TI Midlife Physical Activity Preserves Lower Extremity Function in Older
Adults: Age Gene/Environment Susceptibility-Reykjavik Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE midlife physical activity; mobility; aging; cognitive function; lower
extremity function
ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; CORONARY-HEART-DISEASE;
BODY-COMPOSITION; COGNITIVE IMPAIRMENT; EXECUTIVE FUNCTION; MUSCLE
STRENGTH; GAIT SPEED; DSM-IV; PERFORMANCE; DISABILITY
AB OBJECTIVES: To examine the long-term association between midlife physical activity (PA) and lower extremity function (LEF) in late life.
DESIGN: Longitudinal study with an average of 25 years of follow-up.
SETTING: Community-dwelling old population in Reykjavik, Iceland.
PARTICIPANTS: Four thousand seven hundred fifty-three community-dwelling men and women (mean age 76 +/- 6) in Reykjavik, Iceland.
MEASUREMENTS: On the basis of weekly hours of regular PA reported at the midlife examination, participants were classified as active or inactive. Measures of LEF in late life were gait speed on a 6-m walk, Timed Up and Go (TUG), and knee extension (KE) strength tests. Linear regression analysis was used to examine the association.
RESULTS: Participants who were active in midlife had significantly better LEF (faster gait speed, beta = 0.50, P <= .001; faster TUG time, beta = -0.53 P <= .001; stronger KE strength, beta = 1.3, P <= .001) in late life than those who were not active in midlife after adjusting for sociodemographic and cardiovascular risk factors. After adjustment for cognitive function in late life (speed of processing, memory, and executive function), participants who were active in midlife had significantly faster gait speed (beta = 0.04, P <= .001), faster TUG time (beta = -0.34, P <= .001), and greater KE strength (beta = 0.87, P <= .001) in old age than those who were not active in midlife.
CONCLUSION: Regular PA in midlife is associated with better performance of LEF in later life, even after controlling for late-life cognitive function. J Am Geriatr Soc 61:237-242, 2013.
C1 [Chang, Milan; Snaedal, Jon; Bjornsson, Sigurbjorn; Einarsson, Bjorn; Gudnason, Vilrnundur; Jonsson, Palmi V.] Landspitali Univ Hosp, Geriatr Res Ctr, IS-101 Reykjavik, Iceland.
[Saczynski, Jane S.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA.
[Saczynski, Jane S.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Worcester, MA USA.
[Snaedal, Jon; Jonsson, Palmi V.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Aspelund, Thor] Univ Iceland, Fac Sci, Reykjavik, Iceland.
[Aspelund, Thor; Siggeirsdottir, Kristine; Gudnason, Vilrnundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Garcia, Melissa; Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Chang, M (reprint author), Landspitali Univ Hosp, Geriatr Res Ctr, Aegisgata 26, IS-101 Reykjavik, Iceland.
EM changmilan@gmail.com
RI Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084
FU Intramural Research Program of the National Institutes of Health;
National Institute on Aging [N01-AG-12100]; Icelandic Heart Association;
Landspitali University Hospital; Icelandic Parliament
FX All authors declare no financial interest/conflict of interest. This
study was funded in part by the Intramural Research Program of the
National Institutes of Health, the National Institute on Aging
(N01-AG-12100), the Icelandic Heart Association, Landspitali University
Hospital, and the Icelandic Parliament.
NR 30
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Z9 6
U1 4
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD FEB
PY 2013
VL 61
IS 2
BP 237
EP 242
DI 10.1111/jgs.12077
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 094HY
UT WOS:000315254800009
PM 23320618
ER
PT J
AU Leishear, K
Studenski, SA
Ferrucci, L
de Rekeneire, N
Kritchevsky, SB
Vinik, AI
Hogervorst, E
Harris, TB
Newman, AB
Strotmeyer, ES
AF Leishear, Kira
Studenski, Stephanie A.
Ferrucci, Luigi
de Rekeneire, Nathalie
Kritchevsky, Stephen B.
Vinik, Aaron I.
Hogervorst, Eva
Harris, Tamara B.
Newman, Anne B.
Strotmeyer, Elsa S.
TI VITAMIN B-12 AND PERIPHERAL NERVE FUNCTION IN ELDERLY ADULTS:
"FUNCTIONAL" B-12 DEFICIENCY AS A CONFOUNDING VARIABLE RESPONSE
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Letter
C1 [Leishear, Kira; Newman, Anne B.; Strotmeyer, Elsa S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Leishear, Kira] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA.
[Studenski, Stephanie A.; Newman, Anne B.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med, Pittsburgh, PA 15213 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
[de Rekeneire, Nathalie] Yale Univ, Sch Med, Sect Geriatr, New Haven, CT USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Vinik, Aaron I.] Eastern Virginia Med Sch, Div Endocrinol & Metab, Dept Med, Strelitz Diabet Ctr, Norfolk, VA 23501 USA.
[Hogervorst, Eva] Univ Loughborough, Dept Human Sci, Loughborough, Leics, England.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
RP Leishear, K (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
RI Newman, Anne/C-6408-2013; Strotmeyer, Elsa/F-3015-2014
OI Newman, Anne/0000-0002-0106-1150;
FU NIA NIH HHS [R01 AG028050, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106,
P30 AG024827, P30-AG024827, R01-AG-028050, T32 AG000181, T32-AG-000181];
NINR NIH HHS [R01 NR012459, R01-NR012459]
NR 4
TC 0
Z9 0
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD FEB
PY 2013
VL 61
IS 2
BP 312
EP 313
PG 2
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 094HY
UT WOS:000315254800037
PM 23405939
ER
PT J
AU Kim, HJ
Hagan, M
Butman, JA
Baggenstos, M
Brewer, C
Zalewski, C
Linehan, WM
Lonser, RR
AF Kim, H. Jeffrey
Hagan, Marygrace
Butman, John A.
Baggenstos, Martin
Brewer, Carmen
Zalewski, Christopher
Linehan, W. Marston
Lonser, Russell R.
TI Surgical resection of endolymphatic sac tumors in von Hippel-Lindau
disease: Findings, results, and indications
SO LARYNGOSCOPE
LA English
DT Article
DE Endolymphatic sac tumor; von Hippel-Lindau; hearing loss; outcome;
vertigo; surgery
ID MORBID HEARING-LOSS; COCHLEAR IMPLANTATION; TEMPORAL BONE;
ADENOCARCINOMA; ORIGIN; GENE
AB Objectives/Hypothesis: To define the surgical treatment and outcomes of von Hippel-Lindau (VHL) disease-associated endolymphatic sac tumors (ELSTs), we analyzed consecutive VHL patients who underwent ELST resection. Study Design: Retrospective investigation of consecutive VHL patients who underwent resection of ELSTs at a clinical research center between 1999 and 2010. Methods: Analysis of serial clinical examinations, audiograms, imaging studies, and operative findings were analyzed. Results: Thirty-one consecutive patients with ELSTs (15 males, 16 females) underwent resection of 33 tumors (mean follow-up, 49.9 +/- 48.0 months; range, 1.0116 months). One patient had bilateral ELST resections and one patient underwent reoperation for recurrence. Mean age at surgery was 38.2 +/- 10.2 years (range, 1267 years). Whereas 29 ears (88%) had direct radiographic evidence of an ELST, four ears (12%) did not. Mean tumor size was 1.3 +/- 1.1 cm (range, 0.25.2 cm). Whereas two patients (two ears, 6%) were asymptomatic, 29 patients (31 ears, 94% of ears) had associated audiovestibular symptoms, including sensorineural hearing loss (28 ears, 84%), tinnitus (24 ears,73%), and vertigo (21 patients, 68%). Postoperatively, hearing was stabilized (27) or improved (three) in 97% of 31 ears. Complete tumor resection was achieved in 30 ears (91% of 33 ears). Complications included cerebrospinal fluid leak in two ears (6%) and transient lower cranial nerve palsy in one ear (3%). Conclusions: Surgical resection of ELSTs can be performed with hearing preservation and a reduction in audiovestibular dysfunction. Early surgical resection can prevent or decrease disabling audiovestibular symptoms, enhance the opportunity for complete resection, and preserve hearing. Laryngoscope, 2012
C1 [Kim, H. Jeffrey; Brewer, Carmen; Zalewski, Christopher] Natl Inst Deafness & Other Commun Disorders, Off Clin Director, NIH, Bethesda, MD USA.
[Kim, H. Jeffrey; Brewer, Carmen; Zalewski, Christopher] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Bethesda, MD USA.
[Hagan, Marygrace; Baggenstos, Martin; Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Butman, John A.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Linehan, W. Marston] NIH, Urol Oncol Branch, Natl Canc Ctr, Bethesda, MD 20892 USA.
[Kim, H. Jeffrey] Georgetown Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, Washington, DC 20007 USA.
RP Kim, HJ (reprint author), Georgetown Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, 3800 Reservoir Rd NW, Washington, DC 20007 USA.
EM hk7@georgetown.edu
RI Butman, John/J-2780-2013
OI Butman, John/0000-0002-1547-9195
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke; National Institute on Deafness and Communication
Disorders at the National Institutes of Health
FX This work was funded by the Intramural Research Program of the National
Institute of Neurological Disorders and Stroke and National Institute on
Deafness and Communication Disorders at the National Institutes of
Health.
NR 26
TC 8
Z9 9
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD FEB
PY 2013
VL 123
IS 2
BP 477
EP 483
DI 10.1002/lary.23646
PG 7
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 090NH
UT WOS:000314985400042
PM 23070752
ER
PT J
AU Blouin, AM
Han, SH
Pearce, AM
Cheng, KL
Lee, JJ
Johnson, AW
Wang, CS
During, MJ
Holland, PC
Shaham, Y
Baraban, JM
Reti, IM
AF Blouin, Ashley M.
Han, Sungho
Pearce, Anne M.
Cheng, KaiLun
Lee, JongAh J.
Johnson, Alexander W.
Wang, Chuansong
During, Matthew J.
Holland, Peter C.
Shaham, Yavin
Baraban, Jay M.
Reti, Irving M.
TI Role of medial prefrontal cortex Narp in the extinction of morphine
conditioned place preference
SO LEARNING & MEMORY
LA English
DT Article
ID COCAINE-SEEKING BEHAVIOR; AMPA RECEPTORS; NUCLEUS-ACCUMBENS;
NEURONAL-ACTIVITY; PKM-ZETA; EXCITATORY SYNAPSES; INFRALIMBIC CORTEX;
FEAR EXTINCTION; AMYGDALA; EXPRESSION
AB Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus (AAV) expressing wild-type (WT) Narp into the mPFC of Narp KO mice rescued the extinction and the injection of AAV expressing a dominant negative form of Narp (NarpN) into the mPFC of WT mice impaired the extinction of morphine CPP. These findings suggest that Narp in the mPFC mediates the extinction of morphine CPP.
C1 [Blouin, Ashley M.; Han, Sungho; Cheng, KaiLun; Lee, JongAh J.; Baraban, Jay M.; Reti, Irving M.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Pearce, Anne M.; Johnson, Alexander W.; Holland, Peter C.] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD 21218 USA.
[Wang, Chuansong; During, Matthew J.] Ohio State Univ, Dept Mol Virol Immunol & Mol Genet, Columbus, OH 43210 USA.
[Holland, Peter C.; Baraban, Jay M.; Reti, Irving M.] Johns Hopkins Sch Med, Solomon Snyder Dept Neurosci, Baltimore, MD 21205 USA.
[Shaham, Yavin] NIDA, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
RP Blouin, AM (reprint author), Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
EM ablouin1@jhmi.edu
RI shaham, yavin/G-1306-2014;
OI Baraban, Jay/0000-0002-8165-2638
FU NIDA [5R25DA21630-3]; [RO1 DA016303]
FX We thank Zhi Li and Edward Retzbach for technical assistance. The Narp
antibody was provided by Dr. Paul Worley (Solomon Snyder Department of
Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD). This
work was funded by RO1 DA016303 and NIDA 5R25DA21630-3. The write-up of
this manuscript was also supported in part by funds to the intramural
research program of NIDA.
NR 41
TC 6
Z9 7
U1 1
U2 4
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1072-0502
J9 LEARN MEMORY
JI Learn. Mem.
PD FEB
PY 2013
VL 20
IS 2
BP 75
EP 79
DI 10.1101/lm.028621.112
PG 5
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 093NL
UT WOS:000315198500002
PM 23322555
ER
PT J
AU Clemens, JQ
Clauw, D
Kreder, K
Kusek, J
Lai, H
Rodriguez, L
Williams, D
AF Clemens, J. Quentin
Clauw, Daniel
Kreder, Karl
Kusek, John
Lai, Henry
Rodriguez, Larissa
Williams, David
TI COMPARISON OF BASELINE UROLOGIC SYMPTOMS IN MEN AND WOMEN IN THE
MULTIDISCIPLINARY APPROACH TO THE STUDY OF CHRONIC PELVIC PAIN (MAPP)
RESEARCH COHORT
SO NEUROUROLOGY AND URODYNAMICS
LA English
DT Meeting Abstract
CT Winter Meeting of the Society-for-Urodynamics-and-Female-Urology (SUFU)
CY FEB 26-MAR 02, 2013
CL Las Vegas, NV
SP Soc Urodynam & Female Urol (SUFU)
C1 [Clemens, J. Quentin; Clauw, Daniel; Williams, David] Univ Michigan, Med Ctr, Ann Arbor, MI USA.
[Kreder, Karl] Univ Iowa, Iowa City, IA USA.
[Kusek, John] NIDDK, Bethesda, MD USA.
[Lai, Henry] Washington Univ, St Louis, MO USA.
[Rodriguez, Larissa] Univ Calif Los Angeles, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0733-2467
J9 NEUROUROL URODYNAM
JI Neurourol. Urodyn.
PD FEB
PY 2013
VL 32
IS 2
BP 145
EP 145
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 093WG
UT WOS:000315223200088
ER
PT J
AU Miller, PE
Lazarus, P
Lesko, SM
Cross, AJ
Sinha, R
Laio, J
Zhu, J
Harper, G
Muscat, JE
Hartman, TJ
AF Miller, Paige E.
Lazarus, Philip
Lesko, Samuel M.
Cross, Amanda J.
Sinha, Rashmi
Laio, Jason
Zhu, Jay
Harper, Gregory
Muscat, Joshua E.
Hartman, Terryl J.
TI Meat-Related Compounds and Colorectal Cancer Risk by Anatomical Subsite
SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
LA English
DT Article
ID FOOD FREQUENCY QUESTIONNAIRE; HETEROCYCLIC AMINE EXPOSURE; RED MEAT;
DIETARY PATTERNS; DISTAL COLON; PROSPECTIVE COHORT; DOSE-RESPONSE;
CONSUMPTION; ADENOMA; POLYMORPHISMS
AB Since meat may be involved in the etiology of colorectal cancer, associations between meat-related compounds were examined to elucidate underlying mechanisms in a population-based case-control study. Participants (989 cases/1,033 healthy controls) completed a food frequency questionnaire with a meat-specific module. Multivariable logistic regression was used to examine associations between meat variables and colorectal cancer; polytomous logistic regression was used for subsite-specific analyses. The following significant positive associations were observed for meat-related compounds: 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and colorectal, distal colon, and rectal tumors; 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and colorectal and colon cancer tumors; nitrites/nitrates and proximal colon cancer; 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and rectal cancer; and benzo[a]pyrene and rectal cancer (P-trends < 0.05). For analyses by meat type, cooking method, and doneness preference, positive associations between red processed meat and proximal colon cancer and pan-fried red meat and colorectal cancer were found (P-trends < 0.05). Inverse associations were observed between unprocessed poultry and colorectal, colon, proximal colon, and rectal tumors; grilled/barbequed poultry and proximal colon cancer; and well-done/charred poultry and colorectal, colon, and proximal colon tumors (P-trends < 0.05). HCAs, PAHs, nitrites, and nitrates may be involved in colorectal cancer etiology. Further examination into the unexpected inverse associations between poultry and colorectal cancer is warranted.
C1 [Miller, Paige E.] NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA.
[Lazarus, Philip] Penn State Coll Med, Dept Pharmacol, Hershey, PA USA.
[Lazarus, Philip; Laio, Jason; Zhu, Jay; Muscat, Joshua E.] Penn State Coll Med, Dept Publ Hlth Sci, Hershey, PA USA.
[Lesko, Samuel M.; Laio, Jason; Harper, Gregory; Muscat, Joshua E.; Hartman, Terryl J.] Penn State Canc Inst, Canc Prevent & Control Program, Hershey, PA USA.
[Lesko, Samuel M.] Northeast Reg Canc Inst, Scranton, PA USA.
[Cross, Amanda J.; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Harper, Gregory] Lehigh Valley Hlth Network, Morgan Canc Ctr, Allentown, PA USA.
[Hartman, Terryl J.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA.
RP Miller, PE (reprint author), Exponent Inc, Ctr Epidemiol Biostat & Computat Biol, 525 W Monroe St,Suite 1050, Chicago, IL 60661 USA.
EM pmiller@exponent.com
RI Sinha, Rashmi/G-7446-2015
OI Sinha, Rashmi/0000-0002-2466-7462
FU Pennsylvania Department of Health [4100038714]
FX This research was supported by the Pennsylvania Department of Health
Grant #4100038714. We thank the dedicated staff of this study: Karen
Ryzcak [Northeast Regional Cancer Institute (NRCI)], Gladys Escobar
[Penn State Cancer Institute (PSCI)], Tammy Ryder (PSCI), Christine
Christ (PSCI), Anne Greetcher (PSCI), Wendy Stanton (NRCI), Kimberlee
Welsh (NRCI), PaulineKozik (NRCI), Margaret Fox-Dougherty (NRCI), Nancy
Ziegler (NRCI), Stefanie Crouse (NRCI), Judith Rose (NRCI), Nicholas
Kelly (NRCI), and Corey Lazarus (PSCI). We also would like to
acknowledge the many residents of Pennsylvania for their generous
participation in our study.
NR 64
TC 23
Z9 26
U1 2
U2 37
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0163-5581
EI 1532-7914
J9 NUTR CANCER
JI Nutr. Cancer
PD FEB 1
PY 2013
VL 65
IS 2
BP 202
EP 226
DI 10.1080/01635581.2013.756534
PG 25
WC Oncology; Nutrition & Dietetics
SC Oncology; Nutrition & Dietetics
GA 095RM
UT WOS:000315352200006
PM 23441608
ER
PT J
AU Grigoriu, S
Bond, R
Cossio, P
Chen, JA
Ly, N
Hummer, G
Page, R
Cyert, MS
Peti, W
AF Grigoriu, Simina
Bond, Rachel
Cossio, Pilar
Chen, Jennifer A.
Ly, Nina
Hummer, Gerhard
Page, Rebecca
Cyert, Martha S.
Peti, Wolfgang
TI The Molecular Mechanism of Substrate Engagement and Immunosuppressant
Inhibition of Calcineurin
SO PLOS BIOLOGY
LA English
DT Article
ID CYCLOPHILIN-CYCLOSPORINE-A; PHOSPHATASE-ACTIVITY; PROTEIN PHOSPHATASE;
TRANSCRIPTION FACTOR; CRYSTAL-STRUCTURE; IN-VIVO; COMPLEX; AFFINITY;
DYNAMICS; DEPHOSPHORYLATION
AB Ser/thr phosphatases dephosphorylate their targets with high specificity, yet the structural and sequence determinants of phosphosite recognition are poorly understood. Calcineurin (CN) is a conserved Ca2+/calmodulin-dependent ser/thr phosphatase and the target of immunosuppressants, FK506 and cyclosporin A (CSA). To investigate CN substrate recognition we used X-ray crystallography, biochemistry, modeling, and in vivo experiments to study A238L, a viral protein inhibitor of CN. We show that A238L competitively inhibits CN by occupying a critical substrate recognition site, while leaving the catalytic center fully accessible. Critically, the 1.7 angstrom structure of the A238L-CN complex reveals how CN recognizes residues in A238L that are analogous to a substrate motif, "LxVP." The structure enabled modeling of a peptide substrate bound to CN, which predicts substrate interactions beyond the catalytic center. Finally, this study establishes that "LxVP" sequences and immunosuppressants bind to the identical site on CN. Thus, FK506, CSA, and A238L all prevent "LxVP"-mediated substrate recognition by CN, highlighting the importance of this interaction for substrate dephosphorylation. Collectively, this work presents the first integrated structural model for substrate selection and dephosphorylation by CN and lays the groundwork for structure-based development of new CN inhibitors.
C1 [Grigoriu, Simina; Peti, Wolfgang] Brown Univ, Dept Mol Pharmacol Physiol & Biotechnol, Providence, RI 02912 USA.
[Grigoriu, Simina; Page, Rebecca] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA.
[Bond, Rachel; Chen, Jennifer A.; Ly, Nina; Cyert, Martha S.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
[Cossio, Pilar; Hummer, Gerhard] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Peti, Wolfgang] Brown Univ, Dept Chem, Providence, RI 02912 USA.
RP Grigoriu, S (reprint author), Brown Univ, Dept Mol Pharmacol Physiol & Biotechnol, Providence, RI 02912 USA.
EM mcyert@stanford.edu; wolfgang_peti@brown.edu
RI Peti, Wolfgang/L-3492-2014; Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
FU National Institute of Neurological Disorders and Stroke [R01NS056128];
National Institute of General Medicine and an American Cancer Society
[R01GM098482, RSG-08-067-01-LIB]; National Institute of General Medicine
[R01GM48729]; Intramural Research Program of the National Institute of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health; Departmental NIH [T32-GM007276]; U.S. Department of Energy,
Office of Science, Office of Basic Energy Sciences [DE-AC02-98CH10886]
FX The work was supported by grant R01NS056128 from the National Institute
of Neurological Disorders and Stroke to W.P., grant R01GM098482 from the
National Institute of General Medicine and an American Cancer Society
research scholar grant RSG-08-067-01-LIB to R.P., and grant R01GM48729
from the National Institute of General Medicine to M.S. C.P.C. and G.H.
were supported by the Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health. R.B. was funded by Departmental NIH training grant
T32-GM007276. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.;
The authors thank Dr. M. Allaire (National Synchrotron Light Source,
NSLS) for his support at NSLS beamline X25. Use of the NSLS at
Brookhaven National Laboratory was supported by the U.S. Department of
Energy, Office of Science, Office of Basic Energy Sciences under
contract no. DE-AC02-98CH10886. MD calculations were performed on the
Biowulf computing cluster at NIH. The authors thank Dr. Linda Dixon for
providing information and materials relating to A238L and Dan Herschlag,
Jagoree Roy, and Evan Guiney for helpful discussion and reading of the
manuscript. We thank Dara Dowlatshahi for technical advice and Dr. V.
Kaila (National Institutes of Health) for his support with the quantum
mechanical calculations of the model substrate.
NR 55
TC 36
Z9 37
U1 4
U2 26
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD FEB
PY 2013
VL 11
IS 2
AR e1001492
DI 10.1371/journal.pbio.1001492
PG 13
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 095SR
UT WOS:000315355500016
PM 23468591
ER
PT J
AU Guo, MQ
Huang, BX
AF Guo, Mingquan
Huang, Bill X.
TI Integration of phosphoproteomic, chemical, and biological strategies for
the functional analysis of targeted protein phosphorylation
SO PROTEOMICS
LA English
DT Review
DE Chemical cross-linking; Forward functional analysis; HDX-MS; Kinase
substrates; Phosphoproteomics; Reverse functional analysis; Technology
ID EXCHANGE MASS-SPECTROMETRY; PLECKSTRIN HOMOLOGY DOMAIN; MAMMALIAN
2-HYBRID ASSAYS; C-TERMINAL DOMAIN; CONFORMATIONAL-CHANGES; TYROSINE
KINASE; CROSS-LINKING; QUANTITATIVE PHOSPHOPROTEOMICS;
SIGNAL-TRANSDUCTION; IN-VIVO
AB Reversible phosphorylation, tightly controlled by protein kinases and phosphatases, plays a central role in mediating biological processes, such as proteinprotein interactions, subcellular translocation, and activation of cellular enzymes. MS-based phosphoproteomics has now allowed the detection and quantification of tens of thousands of phosphorylation sites from a typical biological sample in a single experiment, which has posed new challenges in functional analysis of each and every phosphorylation site on specific signaling phosphoproteins of interest. In this article, we review recent advances in the functional analysis of targeted phosphorylation carried out by various chemical and biological approaches in combination with the MS-based phosphoproteomics. This review focuses on three types of strategies, including forward functional analysis, defined for the result-driven phosphoproteomics efforts in determining the substrates of a specific protein kinase; reverse functional analysis, defined for tracking the kinase(s) for specific phosphosite(s) derived from the discovery-driven phosphoproteomics efforts; and MS-based analysis on the structurefunction relationship of phosphoproteins. It is expected that this review will provide a state-of-the-art overview of functional analysis of site-specific phosphorylation and explore new perspectives and outline future challenges.
C1 [Guo, Mingquan] Chinese Acad Sci, Wuhan Bot Garden, Key Lab Plant Germplasm Enhancement & Specialty A, Wuhan 430074, Peoples R China.
[Huang, Bill X.] NIAAA, Lab Mol Signaling, NIH, Bethesda, MD USA.
RP Guo, MQ (reprint author), Chinese Acad Sci, Wuhan Bot Garden, Key Lab Plant Germplasm Enhancement & Specialty A, Wuhan 430074, Peoples R China.
EM zhaoguo2000@yahoo.com; bhuang@mail.nih.gov
NR 108
TC 16
Z9 17
U1 3
U2 63
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1615-9853
EI 1615-9861
J9 PROTEOMICS
JI Proteomics
PD FEB
PY 2013
VL 13
IS 3-4
SI SI
BP 424
EP 437
DI 10.1002/pmic.201200274
PG 14
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 092DO
UT WOS:000315099400003
PM 23125184
ER
PT J
AU Linehan, WM
Ricketts, CJ
AF Linehan, W. Marston
Ricketts, Christopher J.
TI The metabolic basis of kidney cancer
SO SEMINARS IN CANCER BIOLOGY
LA English
DT Review
DE Cancer metabolism; Renal cell carcinoma (RCC); Hereditary kidney cancer;
Cancer metabolism targeted therapy; Warburg effect
ID RENAL-CELL CARCINOMA; HIPPEL-LINDAU-DISEASE; HOGG-DUBE-SYNDROME;
TUMOR-SUPPRESSOR PROTEIN; PARENCHYMAL SPARING SURGERY; TUBEROUS
SCLEROSIS COMPLEX; TYROSINE KINASE DOMAIN; HEREDITARY LEIOMYOMATOSIS;
FUMARATE-HYDRATASE; CHROMOSOME-TRANSLOCATION
AB Kidney cancer is not a single disease; it is made up of a number of different types of cancer that occur in the kidney. Each of these different types of kidney cancer can have a different histology, have a different clinical course, can respond differently to therapy and is caused by a different gene. Kidney cancer is essentially a metabolic disease; each of the known genes for kidney cancer, VHL, MET, FLCN, TSC1, TSC2, TFE3, TFEB, MITF, fumarate hydratase (FH), succinate dehydrogenase B (SDHB), succinate dehydrogenase D (SDHD), and PTEN genes is involved in the cells ability to sense oxygen, iron, nutrients or energy. Understanding the metabolic basis of kidney cancer will hopefully provide the foundation for the development of effective forms of therapy for this disease. Published by Elsevier Ltd.
C1 [Linehan, W. Marston; Ricketts, Christopher J.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, 10 Ctr Dr,MSC 1107,CRC Room 1-5940, Bethesda, MD 20892 USA.
EM WML@nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 94
TC 26
Z9 29
U1 2
U2 16
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-579X
J9 SEMIN CANCER BIOL
JI Semin. Cancer Biol.
PD FEB
PY 2013
VL 23
IS 1
BP 46
EP 55
DI 10.1016/j.semcancer.2012.06.002
PG 10
WC Oncology
SC Oncology
GA 094CI
UT WOS:000315240200007
PM 22705279
ER
PT J
AU Mckew, JC
Pilon, AM
AF McKew, John C.
Pilon, Andre M.
TI NIH TRND program: successes in preclinical therapeutic development
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Editorial Material
C1 [McKew, John C.; Pilon, Andre M.] NIH, Therapeut Rare & Neglected Dis TRND Program, NCATS, Rockville, MD 20850 USA.
RP Mckew, JC (reprint author), NIH, Therapeut Rare & Neglected Dis TRND Program, NCATS, 9800 Med Ctr Dr,Bldg B,Room B3005, Rockville, MD 20850 USA.
EM john.mckew@nih.gov
FU Intramural NIH HHS [ZII HG200364-03]
NR 7
TC 5
Z9 5
U1 2
U2 8
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD FEB
PY 2013
VL 34
IS 2
BP 87
EP 89
DI 10.1016/j.tips.2012.10.001
PG 3
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 096UX
UT WOS:000315431200002
PM 23174531
ER
PT J
AU Wolff, S
Ebihara, H
Groseth, A
AF Wolff, Svenja
Ebihara, Hideki
Groseth, Allison
TI Arenavirus Budding: A Common Pathway with Mechanistic Differences
SO VIRUSES-BASEL
LA English
DT Review
DE arenavirus; budding; ESCRT pathway; matrix protein; nucleoprotein; late
domain
ID VIRUS-LIKE PARTICLES; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; MATRIX
PROTEIN-Z; HEMORRHAGIC-FEVER ARENAVIRUSES; I INTERFERON INDUCTION;
PROLINE-RICH MOTIF; ROUS-SARCOMA-VIRUS; FINGER Z-PROTEIN; LASSA-VIRUS;
SIGNAL PEPTIDE
AB The Arenaviridae is a diverse and growing family of viruses that includes several agents responsible for important human diseases. Despite the importance of this family for public health, particularly in Africa and South America, much of its biology remains poorly understood. However, in recent years significant progress has been made in this regard, particularly relating to the formation and release of new enveloped virions, which is an essential step in the viral lifecycle. While this process is mediated chiefly by the viral matrix protein Z, recent evidence suggests that for some viruses the nucleoprotein (NP) is also required to enhance the budding process. Here we highlight and compare the distinct budding mechanisms of different arenaviruses, concentrating on the role of the matrix protein Z, its known late domain sequences, and the involvement of cellular endosomal sorting complex required for transport (ESCRT) pathway components. Finally we address the recently described roles for the nucleoprotein NP in budding and ribonucleoprotein complex (RNP) incorporation, as well as discussing possible mechanisms related to its involvement.
C1 [Wolff, Svenja] Univ Marburg, Inst Virol, D-35043 Marburg, Germany.
[Ebihara, Hideki; Groseth, Allison] NIAID, Lab Virol, Div Intramural Res, NIH, Hamilton, MT 59840 USA.
RP Groseth, A (reprint author), NIAID, Lab Virol, Div Intramural Res, NIH, Hamilton, MT 59840 USA.
EM wolffs@staff.uni-marburg.de; ebiharah@niaid.nih.gov;
allison.groseth@nih.gov
FU Jurgen Manchot Stiftung; Canadian Institutes of Health Research;
Philipps Universitat Marburg; Division of Intramural Research, NIAID,
NIH
FX The authors are very grateful to Stephen Becker (Philipps Universitat
Marburg) for helpful discussion and Olga Dolnik (Philipps Universitat
Marburg) for conceptual assistance with some of the figures. This work
was funded by grants of the Jurgen Manchot Stiftung (S.W.) and the
Canadian Institutes of Health Research (A.G.) as well being funded in
part by the Philipps Universitat Marburg and the Division of Intramural
Research, NIAID, NIH.
NR 94
TC 7
Z9 7
U1 0
U2 13
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD FEB
PY 2013
VL 5
IS 2
BP 528
EP 549
DI 10.3390/v5020528
PG 22
WC Virology
SC Virology
GA 096HH
UT WOS:000315394300004
PM 23435234
ER
PT J
AU Kerns, EH
AF Kerns, Edward H.
TI Pharmaceutical Profiling Case Study in Disruption
SO ACS MEDICINAL CHEMISTRY LETTERS
LA English
DT Editorial Material
ID DRUG DISCOVERY; OPTIMIZATION; BINDING
C1 NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
RP Kerns, EH (reprint author), NIH, Natl Ctr Adv Translat Sci, 1 Democracy Plaza,9th Floor,6701 Democracy Blvd,M, Bethesda, MD 20892 USA.
EM edward.kerns@nih.gov
NR 9
TC 1
Z9 1
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-5875
J9 ACS MED CHEM LETT
JI ACS Med. Chem. Lett.
PD FEB
PY 2013
VL 4
IS 2
BP 150
EP 152
DI 10.1021/ml300448g
PG 3
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 093HJ
UT WOS:000315182000002
PM 24936241
ER
PT J
AU Yang, ZH
Sun, R
Grinchuk, V
Blanco, JAF
Notari, L
Bohl, JA
McLean, LP
Ramalingam, TR
Wynn, TA
Urban, JF
Vogel, SN
Shea-Donohue, T
Zhao, AP
AF Yang, Zhonghan
Sun, Rex
Grinchuk, Viktoriya
Blanco, Joan Antoni Fernandez
Notari, Luigi
Bohl, Jennifer A.
McLean, Leon P.
Ramalingam, Thirumalai R.
Wynn, Thomas A.
Urban, Joseph F., Jr.
Vogel, Stefanie N.
Shea-Donohue, Terez
Zhao, Aiping
TI IL-33-induced alterations in murine intestinal function and cytokine
responses are MyD88, STAT6, and IL-13 dependent
SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
LA English
DT Article
DE IL-33; intestinal function; IL-13; STAT6; MYD88
ID EPITHELIAL-CELL FUNCTION; NIPPOSTRONGYLUS-BRASILIENSIS INFECTION;
ALTERNATIVELY ACTIVATED MACROPHAGES; SMOOTH-MUSCLE-CELLS; AIRWAY
INFLAMMATION; HELMINTH INFECTION; TYPE-2 IMMUNITY; ENTERIC NERVES;
LYMPHOID-CELLS; MAST-CELLS
AB Yang Z, Sun R, Grinchuk V, Fernandez Blanco JA, Notari L, Bohl JA, McLean LP, Ramalingam TR, Wynn TA, Urban JF, Vogel SN, Shea-Donohue T, Zhao A. IL-33-induced alterations in murine intestinal function and cytokine responses are MyD88, STAT6, and IL-13 dependent. Am J Physiol Gastrointest Liver Physiol 304: G381-G389, 2013. First published December 20, 2012; doi: 10.1152/ajpgi.00357.2012.-IL-33 is a recently identified cytokine member of the IL-1 family. The biological activities of IL-33 are associated with promotion of Th2 and inhibition of Th1/Th17 immune responses. Exogenous IL-33 induces a typical "type 2" immune response in the gastrointestinal tract, yet the underlying mechanisms remain to be fully elucidated. In addition, the role of IL-33 in the regulation of gastrointestinal function is not known. The present study investigated IL-33-dependent intestinal immunity and function in mice. Exogenous IL-33 induced a polarized type 2 cytokine response in the intestine that was entirely MyD88 dependent but STAT6 and IL-13 independent. Mice injected with recombinant IL-33 exhibited intestinal smooth muscle hypercontractility, decreased epithelial responses to acetylcholine and glucose, and increased mucosal permeability. IL-33 effects on intestinal epithelial function were STAT6 dependent, and both IL-4 and IL-13 appeared to play a role. The effects on smooth muscle function, however, were attributable to both STAT6-dependent and -independent mechanisms. In addition, IL-13 induction of insulin-like growth factor-1 was implicated in IL-33-induced smooth muscle hypertrophy. Finally, alternative activation of macrophages induced by IL-33 revealed a novel pathway that is IL-4, IL-13, and STAT6 independent. Thus manipulating IL-33 or related signaling pathways represents a potential therapeutic strategy for treating inflammatory diseases associated with dysregulated intestinal function.
C1 [Yang, Zhonghan; Sun, Rex; Grinchuk, Viktoriya; Blanco, Joan Antoni Fernandez; Notari, Luigi; Bohl, Jennifer A.; McLean, Leon P.; Shea-Donohue, Terez; Zhao, Aiping] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Yang, Zhonghan; Sun, Rex; Grinchuk, Viktoriya; Blanco, Joan Antoni Fernandez; Notari, Luigi; Bohl, Jennifer A.; McLean, Leon P.; Shea-Donohue, Terez; Zhao, Aiping] Univ Maryland, Sch Med, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA.
[Urban, Joseph F., Jr.] ARS, USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD USA.
[Ramalingam, Thirumalai R.; Wynn, Thomas A.] NIAID, Div Parasitol, NIH, Bethesda, MD 20892 USA.
[Vogel, Stefanie N.] Univ Maryland, Sch Med, Dept Microbiol Immunol, Baltimore, MD 21201 USA.
RP Zhao, AP (reprint author), Univ Maryland, Sch Med, Dept Med, 20 Penn St,HSF 2,R S349, Baltimore, MD 21201 USA.
EM azhao@mbrc.umaryland.edu
OI Urban, Joseph/0000-0002-1590-8869
FU National Institutes of Health [DK-083418, AI/DK-49316, AI-18797]; USDA
CRIS [1235-51000-055]
FX This work was supported by National Institutes of Health Grants
DK-083418 (A. Zhao), AI/DK-49316 (T. Shea-Donohue), and AI-18797 (S. N.
Vogel) and USDA CRIS project no. 1235-51000-055 (J. F. Urban). The
opinions and assertions in this article are those of the authors and do
not necessarily represent those of the U.S. Department of Agriculture.
NR 47
TC 17
Z9 17
U1 0
U2 10
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1857
J9 AM J PHYSIOL-GASTR L
JI Am. J. Physiol.-Gastroint. Liver Physiol.
PD FEB
PY 2013
VL 304
IS 4
BP G381
EP G389
DI 10.1152/ajpgi.00357.2012
PG 9
WC Gastroenterology & Hepatology; Physiology
SC Gastroenterology & Hepatology; Physiology
GA 092SW
UT WOS:000315143600008
PM 23257921
ER
PT J
AU Li, LL
Mizel, D
Huang, YN
Eisner, C
Hoerl, M
Thiel, M
Schnermann, J
AF Li, Lingli
Mizel, Diane
Huang, Yuning
Eisner, Christoph
Hoerl, Marion
Thiel, Manfred
Schnermann, Jurgen
TI Tubuloglomerular feedback and renal function in mice with targeted
deletion of the type 1 equilibrative nucleoside transporter
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE stop flow pressure; micropuncture; adenosine; plasma renin; blood
pressure
ID GLOMERULAR-FILTRATION-RATE; ADENOSINE RECEPTORS; IN-VIVO; KNOCKOUT MICE;
KIDNEY; DILAZEP; DIPYRIDAMOLE; RESPONSES; AFFERENT; ABSENCE
AB Li L, Mizel D, Huang Y, Eisner C, Hoerl M, Thiel M, Schnermann J. Tubuloglomerular feedback and renal function in mice with targeted deletion of the type 1 equilibrative nucleoside transporter. Am J Physiol Renal Physiol 304: F382-F389, 2013. First published December 26, 2012; doi:10.1152/ajprenal.00581.2012.-A1 adenosine receptors (A1AR) are required for the modulation of afferent arteriolar tone by changes in luminal NaCl concentration implying that extracellular adenosine concentrations need to change in synchrony with NaCl. The present experiments were performed in mice with a null mutation in the gene for the major equilibrative nucleoside transporter ENT1 to test whether interference with adenosine disposition by cellular uptake of adenosine may modify TGF characteristics. Responses of stop flow pressure (PSF) to maximum flow stimulation were measured in mice with either C57Bl/6 or SWR/J genetic backgrounds. Maximum flow stimulation reduced PSF in ENT1(-/-) compared with wild-type (WT) mice by 1.6 +/- 0.4 mmHg (n = 28) and 5.8 +/- 1.1 mmHg (n = 17; P < 0.001) in C57Bl/6 and by 1.4 +/- 0.4 mmHg (n = 15) and 9 +/- 1.5 mmHg (n = 9; P < 0.001) in SWR/J. Plasma concentrations of adenosine and inosine were markedly higher in ENT1(-/-) than WT mice (ado: 1,179 +/- 78 and 225 +/- 48 pmol/ml; ino: 179 +/- 24 and 47.5 +/- 9 pmol/ml). Renal mRNA expressions of the four adenosine receptors, ENT2, and adenosine deaminase were not significantly different between WT and ENT1(-/-) mice. No significant differences of glomerular filtration rate or mean arterial blood pressure were found while plasma renin concentration, and heart rates were significantly lower in ENT1(-/-) animals. In conclusion, TGF responsiveness is significantly attenuated in the absence of ENT1, pointing to a role of nucleoside transport in the NaCl-synchronous changes of extracellular adenosine levels in the juxtaglomerular apparatus interstitium.
C1 [Li, Lingli; Mizel, Diane; Huang, Yuning; Eisner, Christoph; Schnermann, Jurgen] NIDDK, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA.
[Eisner, Christoph; Thiel, Manfred] Med Fac Mannheim, Dept Anesthesiol, Mannheim, Germany.
[Hoerl, Marion] Univ Munich, Dept Anesthesiol, Munich, Germany.
RP Schnermann, J (reprint author), NIDDK, NIH, Bldg 10,Rm 4D51,10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA.
EM jurgens@intra.niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX This work was supported by the National Institute of Diabetes and
Digestive and Kidney Diseases Intramural Research Program.
NR 39
TC 7
Z9 8
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD FEB
PY 2013
VL 304
IS 4
BP F382
EP F389
DI 10.1152/ajprenal.00581.2012
PG 8
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 092HA
UT WOS:000315109500006
PM 23269643
ER
PT J
AU Nedialkov, YA
Opron, K
Assaf, F
Artsimovitch, I
Kireeva, ML
Kashlev, M
Cukier, RI
Nudler, E
Burton, ZF
AF Nedialkov, Yuri A.
Opron, Kristopher
Assaf, Fadi
Artsimovitch, Irma
Kireeva, Maria L.
Kashlev, Mikhail
Cukier, Robert I.
Nudler, Eygeny
Burton, Zachary F.
TI The RNA polymerase bridge helix YFI motif in catalysis, fidelity and
translocation
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Article
DE RNA polymerase; Bridge helix; Termination; Pausing; Transcriptional
fidelity; Translocation
ID II ELONGATION COMPLEX; TRANSCRIPTION ELONGATION; STRUCTURAL BASIS;
TRIGGER LOOP; REGULATES TRANSCRIPTION; NUCLEOTIDE ADDITION;
MOLECULAR-DYNAMICS; ALLOSTERIC CONTROL; KINETIC-ANALYSIS; SITE
AB The bridge alpha-helix in the beta' subunit of RNA polymerase (RNAP) borders the active site and may have roles in catalysis and translocation. In Escherichia coli RNAP, a bulky hydrophobic segment near the N-terminal end of the bridge helix is identified (beta' 772-YFI-774; the YFI motif). YFI is located at a distance from the active center and adjacent to a glycine hinge (beta' 778-GARKG-782) involved in dynamic bending of the bridge helix. Remarkably, amino acid substitutions in YFI significantly alter intrinsic termination, pausing, fidelity and translocation of RNAP. F773V RNAP largely ignores the lambda tR2 terminator at 200 mu M NTPs and is strongly reduced in lambda tR2 recognition at 1 mu M NTPs. F773V alters RNAP pausing and backtracking and favors misincorporation. By contrast, the adjacent Y772A substitution increases fidelity and exhibits other transcriptional defects generally opposite to those of F773V. All atom molecular dynamics simulation revealed two separate functional connections emanating from YFI explaining the distinct effects of substitutions: Y772 communicates with the active site through the link domain in the beta subunit, whereas F773 communicates through the fork domain in the beta subunit. 1774 interacts with the F-loop, which also contacts the glycine hinge of the bridge helix. These results identified negative and positive circuits coupled at YFI and employed for regulation of catalysis, elongation, termination and translocation. (c) 2012 Elsevier B.V. All rights reserved.
C1 [Nedialkov, Yuri A.; Opron, Kristopher; Assaf, Fadi; Burton, Zachary F.] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA.
[Nedialkov, Yuri A.; Nudler, Eygeny] NYU, Med Ctr, Dept Biochem, New York, NY 10016 USA.
[Artsimovitch, Irma] Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA.
[Kireeva, Maria L.; Kashlev, Mikhail] NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
[Cukier, Robert I.] Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA.
RP Burton, ZF (reprint author), Michigan State Univ, Dept Biochem & Mol Biol, 603 Wilson Rd, E Lansing, MI 48824 USA.
EM burton@cns.msu.edu
OI Nudler, Evgeny/0000-0002-8811-3071
FU National Science Foundation [MCB-1050867]; National Institutes of Health
[R01 GM 092949, R01 GM58750]; Michigan State University; Michigan State
University Agricultural Experiment Station; Michigan State University
College of Osteopathic Medicine
FX This work was supported by the National Science Foundation MCB-1050867
(70%) (to ZFB (PI) and RIC (co-I)) and the National Institutes of Health
R01 GM 092949 (30%) to Michael Feig (PI) and ZFB (co-I). This work was
supported by National Institutes of Health grant R01 GM58750 to EN. ZFB
receives support from Michigan State University, the Michigan State
University Agricultural Experiment Station, and the Michigan State
University College of Osteopathic Medicine. The contents of this
publication do not necessarily reveal the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. government.
NR 40
TC 13
Z9 13
U1 0
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD FEB
PY 2013
VL 1829
IS 2
BP 187
EP 198
DI 10.1016/j.bbagrm.2012.11.005
PG 12
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 091PU
UT WOS:000315063100001
PM 23202476
ER
PT J
AU Zhou, ZL
Yu, PP
Geller, HM
Ober, CK
AF Zhou, Zhaoli
Yu, Panpan
Geller, Herbert M.
Ober, Christopher K.
TI Biomimetic Polymer Brushes Containing Tethered Acetylcholine Analogs for
Protein and Hippocampal Neuronal Cell Patterning
SO BIOMACROMOLECULES
LA English
DT Article
ID TRANSFER RADICAL POLYMERIZATION; SURFACE WETTABILITY; ATTACHMENT;
HYDROGELS; ADHESION; GROWTH; OUTGROWTH; SILICON; CHARGE
AB This paper describes a method to control neuronal cell adhesion and differentiation with both chemical and topographic cues by using a spatially defined polymer brush pattern. First, biomimetic methacrylate polymer brushes containing tethered neurotransmitter acetylcholine functionalities in the form of dimethylaminoethyl methacrylate or free hydroxyl-terminated poly(ethylene glycol) units were prepared using the "grown from" method through surface-initiated atom transfer radical polymerization reactions. The surface properties of the resulting brushes were thoroughly characterized with various techniques and hippocampal neuronal cell culture on the brush surfaces exhibit cell viability and differentiation comparable to, or even better than, those on commonly used poly-L-lysine coated glass coverslips. The polymer brushes were then patterned via UV photolithography techniques to provide specially designed surface features with different sizes (varying from 2 to 200 mu m) and orientations (horizontal and vertical). Protein absorption experiments and hippocampal neuronal cell culture tests on the brush patterns showed that both protein and neurons can adhere to the patterns and therefore be guided by such patterns. These results also demonstrate that, because of their unique chemical composition and well-defined nature, the developed polymer brushes may find many potential applications in cell material interactions studies and neural tissue engineering.
C1 [Zhou, Zhaoli; Ober, Christopher K.] Cornell Univ, Dept Mat Sci & Engn, Ithaca, NY 14853 USA.
[Zhou, Zhaoli; Ober, Christopher K.] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
[Yu, Panpan; Geller, Herbert M.] NHLBI, Dev Neurobiol Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Ober, CK (reprint author), Cornell Univ, Dept Mat Sci & Engn, Ithaca, NY 14853 USA.
EM cko3@cornell.edu
RI Yu, Panpan/A-4962-2013;
OI Geller, Herbert/0000-0002-7048-6144
FU National Science Foundation [DMR-1105253]; ONR Grant [N000141110330];
NIH [NSR01-044287]; NHLBI Division of Intramural Research
FX We thank Dr. Youyong Xu for help with polymer brush preparation, Prof.
E. J. Kramer, Dr. Warren Taylor and Dr. Daniel A. Fisher for XPS and
NEXAFS analysis. We would like to acknowledge the use of the Microscopy
and Imaging Facility at Cornell University, the Cornell Center for
Materials Research (CCMR), the Cornell Nano Scale Science and Technology
Facility (CNF), and the Nanobiotechnology Center (NBTC) at Cornell
University. We also acknowledge the assistance of the NHLBI DIR Light
Microscopy Core Facility. This work was partially supported through the
National Science Foundation (DMR-1105253) and through ONR Grant
(N000141110330), NIH (NSR01-044287), as well as the NHLBI Division of
Intramural Research (P.Y. and H.M.G).
NR 34
TC 16
Z9 16
U1 1
U2 70
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1525-7797
J9 BIOMACROMOLECULES
JI Biomacromolecules
PD FEB
PY 2013
VL 14
IS 2
BP 529
EP 537
DI 10.1021/bm301785b
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science
SC Biochemistry & Molecular Biology; Chemistry; Polymer Science
GA 089KD
UT WOS:000314908500028
PM 23336729
ER
PT J
AU Oh, SY
Kwon, HC
Kim, SH
Lee, S
Lee, JH
Hwang, JA
Hong, SH
Graves, CA
Camphausen, K
Kim, HJ
Lee, YS
AF Oh, Sung Yong
Kwon, Hyuk-Chan
Kim, Sung Hyun
Lee, Suee
Lee, Ji Hyun
Hwang, Jung-Ah
Hong, Seung Hyun
Graves, Christian A.
Camphausen, Kevin
Kim, Hyo-Jin
Lee, Yeon-Su
TI The relationship of Vascular endothelial growth factor gene
polymorphisms and clinical outcome in advanced gastric cancer patients
treated with FOLFOX: VEGF polymorphism in gastric cancer
SO BMC CANCER
LA English
DT Article
DE VEGF; Polymorphism; Gastric cancer
ID GENDER-SPECIFIC ASSOCIATION; GLUTATHIONE-S-TRANSFERASE;
COLORECTAL-CANCER; THYMIDYLATE-SYNTHASE; PROGNOSTIC VALUE; COLON-CANCER;
CHEMOTHERAPY; EXPRESSION; 5-FLUOROURACIL; CARCINOMA
AB Background: The aim of this study is to evaluate the associations between vascular endothelial growth factor (VEGF) Single-nucleotide polymorphisms (SNPs) and clinical outcome in advanced gastric cancer patients treated with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX).
Methods: Genomic DNA was isolated from whole blood, and six VEGF (-2578C/A, -2489C/T, -1498 T/C, -634 G/C, +936C/T, and +1612 G/A) gene polymorphisms were analyzed by PCR. Levels of serum VEGF were measured using enzyme-linked immunoassays.
Results: Patients with G/G genotype for VEGF -634 G/C gene polymorphism showed a lower response rate (22.2%) than those with G/C or C/C genotype (32.3%, 51.1%; P = 0.034). Patients with the VEGF -634 G/C polymorphism G/C + C/C genotype had a longer progression free survival (PFS) of 4.9 months, compared with the PFS of 3.5 months for those with the G/G (P = 0.043, log-rank test). By multivariate analysis, this G/G genotype of VEGF -634 G/C polymorphism was identified as an independent prognostic factor (Hazard ratio 1.497, P = 0.017).
Conclusion: Our data suggest that G/G genotype of VEGF -634 G/C polymorphism is related to the higher serum levels of VEGF, and poor clinical outcome in advanced gastric cancer patients.
C1 [Oh, Sung Yong; Kwon, Hyuk-Chan; Kim, Sung Hyun; Lee, Suee; Lee, Ji Hyun; Kim, Hyo-Jin] Dong A Univ, Coll Med, Dept Internal Med, Pusan, South Korea.
[Hwang, Jung-Ah; Hong, Seung Hyun; Lee, Yeon-Su] Natl Canc Ctr, Res Inst, Canc Genom Branch, Goyang 410769, Gyeonggi Do, South Korea.
[Graves, Christian A.; Camphausen, Kevin] Natl Canc Inst, Radiat Oncol Branch, Bethesda, MD USA.
RP Lee, YS (reprint author), Natl Canc Ctr, Res Inst, Canc Genom Branch, Goyang 410769, Gyeonggi Do, South Korea.
EM yslee2@ncc.re.kr
FU Dong-A University Research Fund
FX This paper was supported by the Dong-A University Research Fund.
NR 31
TC 19
Z9 21
U1 0
U2 4
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 1
PY 2013
VL 13
AR 43
DI 10.1186/1471-2407-13-43
PG 8
WC Oncology
SC Oncology
GA 091CX
UT WOS:000315027700001
PM 23374220
ER
PT J
AU Darragh, TM
Tokugawa, D
Castle, PE
Follansbee, S
Borgonovo, S
LaMere, BJ
Schwartz, L
Gage, JC
Fetterman, B
Lorey, T
Wentzensen, N
AF Darragh, Teresa M.
Tokugawa, Diane
Castle, Philip E.
Follansbee, Stephen
Borgonovo, Sylvia
LaMere, Brandon J.
Schwartz, Lauren
Gage, Julia C.
Fetterman, Barbara
Lorey, Thomas
Wentzensen, Nicolas
TI Interrater agreement of anal cytology
SO CANCER CYTOPATHOLOGY
LA English
DT Article
DE anal cancer screening; cytology; human papillomavirus (HPV); human
immunodeficiency virus (HIV); men who have sex with men (MSM);
biomarkers
ID HUMAN-PAPILLOMAVIRUS; HUMAN IMMUNODEFICIENCY; CANCER; MEN;
HISTOPATHOLOGY; INDIVIDUALS; PROGRAM; LESIONS; RISK
AB BACKGROUND: The majority of anal cancers are caused by persistent infections with carcinogenic human papillomaviruses (HPV). Similar to cervical carcinogenesis, the progression from HPV infection to anal cancer occurs through precancerous lesions that can be treated to prevent invasion. In analogy to cervical cytology, anal cytology has been proposed as a screening tool for anal cancer precursors in high-risk populations. METHODS: The authors analyzed the interobserver reproducibility of anal cytology in a population of 363 human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). Liquid-based cytology (LBC) specimens were collected in the anal dysplasia clinic before the performance of high-resolution anoscopy on all patients. Papanicolaou-stained LBC slides were evaluated by 2 cytopathologists, each of whom was blinded to the clinical outcome and the other pathologist's results, using the revised Bethesda terminology. RESULTS: Overall agreement between the 2 observers was 66% (kappa, 0.54; linear-weighted kappa, 0.69). Using dichotomizing cytology results (atypical squamous cells of undetermined significance [ASC-US] or worse vs less than ASC-US), the agreement increased to 86% (kappa, 0.69). An increasing likelihood of testing positive for markers associated with HPV-related transformation, p16/Ki-67, and HPV oncogene messenger RNA was observed, with increasing severity of cytology results noted both for individual cytologists and for consensus cytology interpretation (P value for trend [ptrend] < .0001 for all). CONCLUSIONS: Moderate to good agreement was observed between 2 cytopathologists evaluating anal cytology samples collected from HIV-positive MSM. A higher severity of anal cytology was associated with biomarkers of anal precancerous lesions. Anal cytology may be used for anal cancer screening in high-risk populations, and biomarkers of HPV-related transformation can serve as quality control for anal cytology. Cancer (Cancer Cytopathol) 2013. Published 2012 by the American Cancer Society.
C1 [Darragh, Teresa M.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA.
[Tokugawa, Diane; LaMere, Brandon J.; Fetterman, Barbara; Lorey, Thomas] Kaiser Permanente, TPMG Reg Lab, Berkeley, CA USA.
[Castle, Philip E.] Amer Soc Clin Pathol Inst, Washington, DC USA.
[Follansbee, Stephen; Borgonovo, Sylvia] Kaiser Permanente Med Ctr, Dept Med, Div Infect Dis, San Francisco, CA USA.
[Schwartz, Lauren; Gage, Julia C.; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 5024, Rockville, MD 20852 USA.
EM wentzenn@mail.nih.gov
FU Intramural Research Program of the National Institutes of
Health/National Cancer Institute
FX Supported by the Intramural Research Program of the National Institutes
of Health/National Cancer Institute.
NR 20
TC 15
Z9 16
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1934-662X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD FEB
PY 2013
VL 121
IS 2
BP 72
EP 78
DI 10.1002/cncy.21218
PG 7
WC Oncology; Pathology
SC Oncology; Pathology
GA 090NQ
UT WOS:000314986300004
PM 22811048
ER
PT J
AU Mitchem, JB
Brennan, DJ
Knolhoff, BL
Belt, BA
Zhu, Y
Sanford, DE
Belaygorod, L
Carpenter, D
Collins, L
Piwnica-Worms, D
Hewitt, S
Udupi, GM
Gallagher, WM
Wegner, C
West, BL
Wang-Gillam, A
Goedegebuure, P
Linehan, DC
DeNardo, DG
AF Mitchem, Jonathan B.
Brennan, Donal J.
Knolhoff, Brett L.
Belt, Brian A.
Zhu, Yu
Sanford, Dominic E.
Belaygorod, Larisa
Carpenter, Danielle
Collins, Lynne
Piwnica-Worms, David
Hewitt, Stephen
Udupi, Girish Mallya
Gallagher, William M.
Wegner, Craig
West, Brian L.
Wang-Gillam, Andrea
Goedegebuure, Peter
Linehan, David C.
DeNardo, David G.
TI Targeting Tumor-Infiltrating Macrophages Decreases Tumor-Initiating
Cells, Relieves Immunosuppression, and Improves Chemotherapeutic
Responses
SO CANCER RESEARCH
LA English
DT Article
ID CANCER STEM-CELLS; PANCREATIC DUCTAL ADENOCARCINOMA; BREAST-CANCER;
INFLAMMATORY MONOCYTES; MYELOID CELLS; GROWTH-FACTOR; MICE; METASTASIS;
IMMUNITY; MICROENVIRONMENT
AB Tumor-infiltrating immune cells can promote chemoresistance and metastatic spread in aggressive tumors. Consequently, the type and quality of immune responses present in the neoplastic stroma are highly predictive of patient outcome in several cancer types. In addition to host immune responses, intrinsic tumor cell activities that mimic stem cell properties have been linked to chemoresistance, metastatic dissemination, and the induction of immune suppression. Cancer stem cells are far from a static cell population; rather, their presence seems to be controlled by highly dynamic processes that are dependent on cues from the tumor stroma. However, the impact immune responses have on tumor stem cell differentiation or expansion is not well understood. In this study, we show that targeting tumor-infiltrating macrophages (TAM) and inflammatory monocytes by inhibiting either the myeloid cell receptors colony-stimulating factor-1 receptor (CSF1R) or chemokine (C-C motif) receptor 2 (CCR2) decreases the number of tumor-initiating cells (TIC) in pancreatic tumors. Targeting CCR2 or CSF1R improves chemotherapeutic efficacy, inhibits metastasis, and increases antitumor T-cell responses. Tumor-educated macrophages also directly enhanced the tumor-initiating capacity of pancreatic tumor cells by activating the transcription factor STAT3, thereby facilitating macrophage-mediated suppression of CD8(+) T lymphocytes. Together, our findings show how targeting TAMs can effectively overcome therapeutic resistance mediated by TICs. Cancer Res; 73(3); 1128-41. (c) 2012 AACR.
C1 [Mitchem, Jonathan B.; Belt, Brian A.; Sanford, Dominic E.; Goedegebuure, Peter; Linehan, David C.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
[Knolhoff, Brett L.; Zhu, Yu; Belaygorod, Larisa; Wang-Gillam, Andrea; DeNardo, David G.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Carpenter, Danielle; DeNardo, David G.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Collins, Lynne; Piwnica-Worms, David] Washington Univ, Sch Med, Mol Imaging Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
[Collins, Lynne; Piwnica-Worms, David] Washington Univ, Sch Med, BRIGHT Inst, St Louis, MO 63110 USA.
[Piwnica-Worms, David; Goedegebuure, Peter; Linehan, David C.; DeNardo, David G.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA.
[Wegner, Craig] Pfizer Inc, St Louis, MO USA.
[Hewitt, Stephen] NCI, Adv Technol Ctr, Bethesda, MD 20892 USA.
[West, Brian L.] Plexxikon Inc, Berkeley, CA USA.
[Brennan, Donal J.] Univ Queensland, Queensland Ctr Gynaecol Canc, Cent Clin Div, Sch Med, Brisbane, Qld, Australia.
[Udupi, Girish Mallya; Gallagher, William M.] Univ Coll Dublin, UCD Conway Inst, UCD Sch Biomol & Biomed Sci, Dublin 2, Ireland.
RP DeNardo, DG (reprint author), Washington Univ, Sch Med, Dept Med, 660 S Euclid Ave,Box 8069, St Louis, MO 63110 USA.
EM ddenardo@dom.wustl.edu
OI Hewitt, Stephen/0000-0001-8283-1788; Mitchem,
Jonathan/0000-0002-5385-7038; Gallagher, William/0000-0002-4307-5999
FU Pfizer Oncology; Novartis Oncology; WU/Pfizer Biomedical Research Grant
[PW0457]; NIH [P50 CA 94056]; NCI grant [T32 CA 009621]
FX D.J. Brennan has ownership interest (including patents) in patent for
CD8: CD68 signature. D.C. Linehan has other commercial research support
from Pfizer Oncology and Novartis Oncology. No potential conflicts of
interest were disclosed by the other authors.; This study was supported
by WU/Pfizer Biomedical Research Grant PW0457 (D.C. Linehan), NIH P50 CA
94056 (D. Piwnica-Worms), and NCI grant T32 CA 009621 (J.B. Mitchem and
D.E. Sanford).
NR 48
TC 163
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U1 11
U2 57
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD FEB 1
PY 2013
VL 73
IS 3
BP 1128
EP 1141
DI 10.1158/0008-5472.CAN-12-2731
PG 14
WC Oncology
SC Oncology
GA 091DD
UT WOS:000315028300011
PM 23221383
ER
PT J
AU Baidoo, KE
Yong, K
Brechbiel, MW
AF Baidoo, Kwamena E.
Yong, Kwon
Brechbiel, Martin W.
TI Molecular Pathways: Targeted alpha-Particle Radiation Therapy
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID DOUBLE-STRAND BREAKS; MYELOID-LEUKEMIA; CELL-DEATH; RADIOIMMUNOTHERAPY;
DOSIMETRY; PHARMACOKINETICS; IMMUNOTHERAPY; IRRADIATION; MECHANISMS;
INDUCTION
AB An alpha-particle, a He-4 nucleus, is exquisitely cytotoxic and indifferent to many limitations associated with conventional chemo-and radiotherapy. The exquisite cytotoxicity of alpha-radiation, the result of its high mean energy deposition [high linear energy transfer (LET)] and limited range in tissue, provides for a highly controlled therapeutic modality that can be targeted to selected malignant cells [targeted alpha-therapy (TAT)] with minimal normal tissue effects. A burgeoning interest in the development of TAT is buoyed by the increasing number of ongoing clinical trials worldwide. The short path length renders alpha-emitters suitable for treatment and management of minimal disease such as micrometastases or residual tumor after surgical debulking, hematologic cancers, infections, and compartmental cancers such as ovarian cancer or neoplastic meningitis. Yet, despite decades of study of high LET radiation, the mechanistic pathways of the effects of this modality remain not well defined. The modality is effectively presumed to follow a simple therapeutic mechanism centered on catastrophic double-strand DNA breaks without full examination of the actual molecular pathways and targets that are activated that directly affect cell survival or death. This Molecular Pathways article provides an overview of the mechanisms and pathways that are involved in the response to and repair of TAT-induced DNA damage as currently understood. Finally, this article highlights the current state of clinical translation of TAT as well as other high-LET radionuclide radiation therapy using alpha-emitters such as Ac-225, At-211, Bi-213, Pb-212, and Ra-223. Clin Cancer Res; 19(3); 530-7. (C)2012 AACR.
C1 [Baidoo, Kwamena E.; Yong, Kwon; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Rm B3B69, Bethesda, MD 20892 USA.
EM martinwb@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
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PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD FEB 1
PY 2013
VL 19
IS 3
BP 530
EP 537
DI 10.1158/1078-0432.CCR-12-0298
PG 8
WC Oncology
SC Oncology
GA 088UQ
UT WOS:000314863000005
PM 23230321
ER
PT J
AU Ferris, M
Norwood, V
Radeva, M
Gassman, JJ
Al-Uzri, A
Askenazi, D
Matoo, T
Pinsk, M
Sharma, A
Smoyer, W
Stults, J
Vyas, S
Weiss, R
Gipson, D
Kaskel, F
Friedman, A
Moxey-Mims, M
Trachtman, H
AF Ferris, Maria
Norwood, Victoria
Radeva, Milena
Gassman, Jennifer J.
Al-Uzri, Amira
Askenazi, David
Matoo, Tej
Pinsk, Maury
Sharma, Amita
Smoyer, William
Stults, Jenna
Vyas, Shefali
Weiss, Robert
Gipson, Debbie
Kaskel, Frederick
Friedman, Aaron
Moxey-Mims, Marva
Trachtman, Howard
TI Patient Recruitment into a Multicenter Randomized Clinical Trial for
Kidney Disease: Report of the Focal Segmental Glomerulosclerosis
Clinical Trial (FSGS CT)
SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE
LA English
DT Article
DE clinical trials; kidney; nephrology; pediatrics
ID RARE DISEASES; ENROLLMENT; CHILDREN
AB We describe the experience of the focal segmental glomerulosclerosis clinical trial (FSGS CT) in the identification and recruitment of participants into the study. This National Institutes of Health funded study, a multicenter, open-label, randomized comparison of cyclosporine versus oral dexamethasone pulses plus mycophenolate mofetil, experienced difficulty and delays meeting enrollment goals. These problems occurred despite the support of patient advocacy groups and aggressive recruitment strategies. Multiple barriers were identified including: (1) inaccurate estimates of the number of potential incident FSGS patients at participating centers; (2) delays in securing one of the test agents; (3) prolonged time between IRB approval and execution of a subcontract (mean 7.5 +/- 0.8 months); (4) prolonged time between IRB approval and enrollment of the first patient at participating sites (mean 19.6 +/- 1.4 months); and (5) reorganization of clinical coordinating core infrastructure to align resources with enrollment. A Web-based anonymous survey of site investigators revealed site-related barriers to patient recruitment. The value of a variety of recruitment tools was of marginal utility in facilitating patient enrollment. We conclude that improvements in the logistics of study approval and regulatory start-up and testing of promising novel agents are important factors in promoting enrollment into randomized clinical trials in nephrology. Clin Trans Sci 2013; Volume 6: 1320
C1 [Ferris, Maria] Univ N Carolina, Chapel Hill, NC USA.
[Norwood, Victoria] Univ Virginia, Charlottesville, VA USA.
[Radeva, Milena; Gassman, Jennifer J.] Cleveland Clin, Cleveland, OH 44106 USA.
[Al-Uzri, Amira] Doernbecher Childrens Hosp, Portland, OR USA.
[Askenazi, David] Univ Alabama Birmingham, Birmingham, AL USA.
[Matoo, Tej] Childrens Hosp Michigan, Detroit, MI 48201 USA.
[Pinsk, Maury] Univ Alberta, Edmonton, AB, Canada.
[Sharma, Amita] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Smoyer, William] Nationwide Childrens Hosp, Columbus, OH USA.
[Stults, Jenna] Seattle Childrens Hosp, Seattle, WA USA.
[Vyas, Shefali] St Barnabas Hosp, Livingston, NJ USA.
[Weiss, Robert] New York Med Coll, Valhalla, NY 10595 USA.
[Gipson, Debbie] Univ Michigan, Ann Arbor, MI 48109 USA.
[Kaskel, Frederick] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Friedman, Aaron] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Moxey-Mims, Marva] NIDDK, NIH, Bethesda, MD USA.
[Trachtman, Howard] NYU Langone Med Ctr, New York, NY USA.
RP Trachtman, H (reprint author), NYU Langone Med Ctr, New York, NY USA.
EM howard.trachtman@nyumc.org
OI Pinsk, Maury/0000-0001-7668-665X; Trachtman, Howard/0000-0001-7447-9489
FU NIH-NIDDK [U01-DK063385, DK063490, DK063455, DK063549]; National Center
for Research Resources: University of North Carolina [UL1 RR025747];
National Center for Research Resources: University of Michigan [UL1
RR0249860]; National Center for Research Resources: Harvard University
[UL1 RR05758]; National Center for Research Resources: Albert Einstein
College of Medicine [UL1 RR025750]; National Center for Research
Resources: Medical University of South Carolina [UL1 RR029882]
FX This study was sponsored by the NIH-NIDDK Grants U01-DK063385, DK063490,
DK063455, and DK063549. In addition, the trial was supported by the
following Clinical and Translational Science Awards from the National
Center for Research Resources: University of North Carolina (UL1
RR025747), University of Michigan (UL1 RR0249860), Harvard University
(UL1 RR05758), Albert Einstein College of Medicine (UL1 RR025750), and
Medical University of South Carolina (UL1 RR029882). The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Center for Research
Resources or the National Institutes of Health. Th e authors thank
Edward Iglesia for his assistance in preparing Figure 2.
NR 21
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U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1752-8054
J9 CTS-CLIN TRANSL SCI
JI CTS-Clin. Transl. Sci.
PD FEB
PY 2013
VL 6
IS 1
BP 13
EP 20
DI 10.1111/cts.12003
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 089OK
UT WOS:000314919700007
PM 23399084
ER
PT J
AU Price, DW
Ma, Y
Rubin, RR
Perreault, L
Bray, GA
Marrero, D
Knowler, WC
Barrett-Connor, E
LaCoursiere, DY
AF Price, David W.
Ma, Yong
Rubin, Richard R.
Perreault, Leigh
Bray, George A.
Marrero, David
Knowler, William C.
Barrett-Connor, Elizabeth
LaCoursiere, D. Yvette
CA Diabet Prevention Program Res Grp
TI Depression as a Predictor of Weight Regain Among Successful Weight
Losers in the Diabetes Prevention Program
SO DIABETES CARE
LA English
DT Article
ID ANTIDEPRESSANT MEDICINE USE; LIFE-STYLE; SELF-CARE; SYMPTOMS; OBESITY;
RISK; PARTICIPANTS; METAANALYSIS; ASSOCIATION; DIAGNOSIS
AB OBJECTIVE-To determine whether depression symptoms or antidepressant medication use predicts weight regain in overweight individuals with impaired glucose tolerance (IGT) who are successful with initial weight loss.
RESEARCH DESIGN AND METHODS-A total of 1,442 participants who successfully lost at least 3% of their baseline body weight after 12 months of participation in the randomized controlled Diabetes Prevention Program (DPP) continued in their assigned treatment group (metformin, intensive lifestyle, or placebo) and were followed into the Diabetes Prevention Program Outcome Study (DPPOS). Weight regain was defined as a return to baseline DPP body weight. Participant weight and antidepressant medication use were assessed every 6 months. Depression symptoms (Beck Depression Inventory [BDI] score >= 11) were assessed every 12 months.
RESULTS-Only 2.7% of the overall cohort had moderate to severe depression symptoms at baseline; most of the participants with BDI score >= 11 had only mild symptoms during the period of observation. In unadjusted analyses, both depression symptoms (hazard ratio 1.31 [95% CI 1.03-1.67], P = 0.03) and antidepressant medication use at either the previous visit (1.72 [1.37-2.15], P < 0.0001) or cumulatively as percent of visits (1.005 [1.002-1.008], P = 0.0003) were predictors of subsequent weight regain. After adjustment for multiple covariates, antidepressant use remained a significant predictor of weight regain (P < 0.0001 for the previous study visit; P = 0.0005 for the cumulative measure), while depression symptoms did not.
CONCLUSIONS-In individuals with IGT who do not have severe depression and who initially lose weight, antidepressant use may increase the risk of weight regain. Diabetes Care 36: 216-221, 2013
C1 [Price, David W.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA.
[Price, David W.] Univ Colorado, Dept Family Med, Aurora, CO USA.
[Ma, Yong] George Washington Univ, Ctr Biostat, Rockville, MD USA.
[Rubin, Richard R.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Rubin, Richard R.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Perreault, Leigh] Univ Colorado, Dept Endocrinol, Aurora, CO USA.
[Bray, George A.] Pennington Biomed Res Ctr, Baton Rouge, LA USA.
[Marrero, David] Indiana Univ Sch Med, Dept Med, Indianapolis, IN USA.
[Knowler, William C.] NIDDK, Phoenix, AZ USA.
[Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[LaCoursiere, D. Yvette] Univ Calif San Diego, Dept Reprod Med, La Jolla, CA 92093 USA.
RP Price, DW (reprint author), Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA.
EM dppmail@biostat.bsc.gwu.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
of the National Institutes of Health; NIDDK; Indian Health Service;
National Institute of Child Health and Human Development; National
Institute on Aging; National Eye Institute; National Heart, Lung and
Blood Institute; Office of Research on Women's Health; National
Institute on Minority Health and Health Disparities; Centers for Disease
Control and Prevention; American Diabetes Association; Bristol-Myers
Squibb; Parke-Davis
FX During the DPPOS, the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) of the National Institutes of Health provided
funding to the clinical centers and the coordinating center for the
design and conduct of the study and collection, management, analysis,
and interpretation of the data. The Southwestern American Indian Centers
were supported directly by the NIDDK, including its Intramural Research
Program, and the Indian Health Service. The General Clinical Research
Center Program, National Center for Research Resources, supported data
collection at many of the clinical centers. Funding was also provided by
the National Institute of Child Health and Human Development, the
National Institute on Aging, the National Eye Institute, the National
Heart, Lung and Blood Institute, the Office of Research on Women's
Health, the National Institute on Minority Health and Health
Disparities, the Centers for Disease Control and Prevention, and the
American Diabetes Association.; Bristol-Myers Squibb and Parke-Davis
provided additional funding and material support during the DPP. Lipha
(Merck-Sante) provided medication, and LifeScan Inc. donated materials
during the DPP and DPPOS. No other potential conflicts of interest
relevant to this article were reported.
NR 26
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PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD FEB
PY 2013
VL 36
IS 2
BP 216
EP 221
DI 10.2337/dc12-0293
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 083MA
UT WOS:000314467100016
PM 23002085
ER
PT J
AU Pomeroy, J
Renstrom, F
Gradmark, AM
Mogren, I
Persson, M
Bluck, L
Wright, A
Kahn, SE
Domellof, M
Franks, PW
AF Pomeroy, Jeremy
Renstrom, Frida
Gradmark, Anna M.
Mogren, Ingrid
Persson, Margareta
Bluck, Les
Wright, Antony
Kahn, Steven E.
Domellof, Magnus
Franks, Paul W.
TI Maternal Physical Activity and Insulin Action in Pregnancy and Their
Relationships With Infant Body Composition
SO DIABETES CARE
LA English
DT Article
ID SENSITIVITY; WOMEN; SECRETION
AB OBJECTIVE-We sought to assess the association between maternal gestational physical activity and insulin action and body composition in early infancy.
RESEARCH DESIGN AND METHODS-At 28-32 weeks' gestation, pregnant women participating in an observational study in Sweden underwent assessments of height, weight, and body composition, an oral glucose tolerance test, and 10 days of objective physical activity assessment. Thirty mothers and infants returned at 11-19 weeks postpartum. Infants underwent assessments of weight, length, and body composition.
RESULTS-Early insulin response was correlated with total physical activity (r = 0.47; P = 0.007). Early insulin response (r = -0.36; P = 0.045) and total physical activity (r = 0.52; P = 0.037) were also correlated with infant fat-free mass. No maternal variable was significantly correlated with infant adiposity.
CONCLUSIONS-The relationships between maternal physical activity, insulin response, and infant fat-free mass suggest that physical activity during pregnancy may affect metabolic outcomes in the mother and her offspring. Diabetes Care 36:267-269, 2013
C1 [Pomeroy, Jeremy; Renstrom, Frida; Franks, Paul W.] Lund Univ, Skane Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.
[Pomeroy, Jeremy] NIH, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA.
[Renstrom, Frida; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Renstrom, Frida; Gradmark, Anna M.; Franks, Paul W.] Umea Univ, Med Sect, Genet Epidemiol & Clin Res Grp, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Mogren, Ingrid; Persson, Margareta] Umea Univ, Dept Clin Sci, Obstet & Gynecol Unit, Umea, Sweden.
[Persson, Margareta] Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
[Bluck, Les; Wright, Antony] MRC Human Nutr Res, Cambridge, England.
[Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA.
[Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA.
[Domellof, Magnus] Umea Univ, Dept Pediat, Umea, Sweden.
RP Franks, PW (reprint author), Lund Univ, Skane Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.
EM jeremy.pomeroy@nih.gov; paul.franks@med.lu.se
RI Domellof, Magnus/E-5307-2011;
OI Domellof, Magnus/0000-0002-0726-7029; Mogren,
Ingrid/0000-0003-2985-1135; Franks, Paul/0000-0002-0520-7604; Kahn,
Steven/0000-0001-7307-9002
FU Torsten Soderberg foundation; Ragnar Soderberg foundation; Fredrik and
Ingrid Thurings Foundation; Vasterbotten regional health authority;
Medical Research Council Unit [U1059]; National Institute of Diabetes
and Digestive and Kidney Diseases; U.S. Department of Veterans Affairs
FX This study was a preparatory project for the LifeGene Study
(www.lifegene.se) and was funded by the Torsten and Ragnar Soderberg
foundations, Fredrik and Ingrid Thurings Foundation, and Vasterbotten
regional health authority (all grants to P.W.F.). The stable isotope
measurements were conducted under the Medical Research Council Unit
Program U1059. J.P. was supported by the National Institute of Diabetes
and Digestive and Kidney Diseases Intramural Research Program. S.E.K.
was supported in part by the U.S. Department of Veterans Affairs.
NR 9
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U1 0
U2 11
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD FEB
PY 2013
VL 36
IS 2
BP 267
EP 269
DI 10.2337/dc12-0885
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 083MA
UT WOS:000314467100023
PM 22966095
ER
PT J
AU Lin, SSX
Berlin, I
Younge, R
Jin, ZZ
Sibley, CT
Schreiner, P
Szklo, M
Bertoni, AG
AF Lin, Susan X.
Berlin, Ivan
Younge, Richard
Jin, Zhezhen
Sibley, Christopher T.
Schreiner, Pamela
Szklo, Moyses
Bertoni, Alain G.
TI Does Elevated Plasma Triglyceride Level Independently Predict Impaired
Fasting Glucose? The Multi-Ethnic Study of Atherosclerosis (MESA)
SO DIABETES CARE
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; TYPE-2 DIABETES-MELLITUS; LIFE-STYLE
INTERVENTION; METABOLIC SYNDROME; INSULIN-RESISTANCE;
CARDIOVASCULAR-DISEASE; NATIONAL-HEALTH; US POPULATION; YOUNG MEN;
TOLERANCE
AB OBJECTIVE-Elevated plasma triglycerides (TGs) have been included in diabetes risk prediction models. This study examined whether elevated TGs predict risk for impaired fasting glucose (IFG).
RESEARCH DESIGN AND METHODS-This study used the baseline and longitudinal follow-up data from the Multi-Ethnic Study of Atherosclerosis (MESA). The analysis included non-Hispanic whites, African Americans, Hispanics, and Chinese Americans 45-84 years of age who had fasting glucose <100 mg/dL at baseline and who did not have clinically evident cardiovascular disease or diabetes. Cox proportional regression models were used to examine the association of elevated TGs with incidence of IFG adjusting for central obesity, low HDL cholesterol, elevated blood pressure, baseline fasting glucose, and BMI. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of elevated TGs in predicting IFG were calculated.
RESULTS-The incidence rate of developing IFG was 59.1 per 1,000 person-years during the median 4.75 years of follow-up. African Americans and Hispanics had a higher incidence rate of IFG compared with non-Hispanic whites among people with normal TG concentrations. Elevated TGs (>150 mg/dL) at baseline were independently associated with the incidence of IFG with an adjusted hazard ratio of 1.19 (95% CI 1.04-1.37). However, its predictive value for identifying people at risk for IFG was poor, with <57% AUC. Interactions of elevated TGs with race/ethnicity in predicting IFG were not statistically significant.
CONCLUSIONS-Elevated TGs were moderately associated with risk for IFG, and it was a poor risk prediction tool for IFG. Diabetes Care 36:342-347, 2013
C1 [Lin, Susan X.; Younge, Richard] Columbia Univ, Ctr Family & Community Med, New York, NY 10027 USA.
[Berlin, Ivan] Univ Paris 06, AP HP, Hop La Pitie Salpetriere, Fac Med,INSERM,U894, Paris, France.
[Jin, Zhezhen] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA.
[Sibley, Christopher T.] NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Schreiner, Pamela] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Szklo, Moyses] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Bertoni, Alain G.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
RP Lin, SSX (reprint author), Columbia Univ, Ctr Family & Community Med, New York, NY 10027 USA.
EM xl18@columbia.edu
RI Sibley, Christopher/C-9900-2013
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]
FX The MESA study was supported by contracts N01-HC-95159 through
N01-HC-95169 from the National Heart, Lung, and Blood Institute.
NR 38
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U1 2
U2 12
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD FEB
PY 2013
VL 36
IS 2
BP 342
EP 347
DI 10.2337/dc12-0355
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 083MA
UT WOS:000314467100036
PM 23033247
ER
PT J
AU Buse, JB
Kaufman, FR
Linder, B
Hirst, K
El Ghormli, L
Willi, S
AF Buse, John B.
Kaufman, Francine R.
Linder, Barbara
Hirst, Kathryn
El Ghormli, Laure
Willi, Steven
CA Hlth Study Grp
TI Diabetes Screening With Hemoglobin A(1c) Versus Fasting Plasma Glucose
in a Multiethnic Middle-School Cohort
SO DIABETES CARE
LA English
DT Article
ID A1C
AB OBJECTIVE-To characterize middle-school students from the HEALTHY study with glycemic abnormalities, specifically high-risk hemoglobin A(1c) (A1C) (hrA1C; A1C = 5.7-6.4%) and impaired fasting glucose (IFG; fasting plasma glucose [FPG] = 100-125 mg/dL).
RESEARCH DESIGN AND METHODS-History was collected by self-report, physical measurement was collected by trained study staff, and fasting blood was drawn by trained phlebotomists and analyzed centrally.
RESULTS-At baseline, among 3,980 sixth graders, 128 (3.2%) had hrA1C and 635 (16.0%) had IFG. Compared with A1C <5.7%, hrA1C was associated with non-Hispanic black race/ethnicity, family history of diabetes, and higher measurements of BMI, waist circumference, and fasting insulin. Compared with FPG <100 mg/dL, IFG was associated with Hispanic ethnicity; increased BMI, waist circumference, and fasting insulin; higher frequency of high blood pressure; and higher mean triglycerides. Two years later, children with hrA1C persisted as hrA1C in 59.4%, and one child (0.8%) developed A1C >= 6.5%; children with IFG persisted with IFG in 46.9%, and seven children (1.1%) developed FPG >= 126 mg/dL. Those with hrA1C compared with IFG had a higher BMI in sixth grade, which persisted to eighth grade.
CONCLUSIONS-In the HEALTHY study cohort, hrA1C and IFG define different groups of youth with differentially increased diabetes risk markers. IFG is approximately fivefold more common, but hrA1C is more persistent over time. Optimal screening strategies for diabetes in youth remain unresolved. Diabetes Care 36:429-435, 2013
C1 [Buse, John B.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Kaufman, Francine R.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Linder, Barbara] NIDDKD, Bethesda, MD 20892 USA.
[Hirst, Kathryn; El Ghormli, Laure] George Washington Univ, Ctr Biostat, Rockville, MD USA.
[Willi, Steven] Childrens Hosp Philadelphia, Dept Endocrinol & Diabet, Philadelphia, PA 19104 USA.
RP Hirst, K (reprint author), George Washington Univ, Ctr Biostat, Rockville, MD USA.
EM khirst@bsc.gwu.edu
FU National Institute of Diabetes and Digestive and Kidney
Diseases/National Institutes of Health [U01-DK-61230, U01-DK-61249,
U01-DK-61231, U01-DK-61223]; American Diabetes Association
FX This work was completed with funding from the National Institute of
Diabetes and Digestive and Kidney Diseases/National Institutes of Health
grants U01-DK-61230, U01-DK-61249, U01-DK-61231, and U01-DK-61223, with
additional support from the American Diabetes Association.
NR 15
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U1 0
U2 5
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD FEB
PY 2013
VL 36
IS 2
BP 429
EP 435
DI 10.2337/dc12-0295
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 083MA
UT WOS:000314467100048
PM 23193207
ER
PT J
AU Neofytos, D
Lu, K
Hatfield-Seung, A
Blackford, A
Marr, KA
Treadway, S
Ostrander, D
Nussenblatt, V
Karp, J
AF Neofytos, Dionissios
Lu, Kit
Hatfield-Seung, Amy
Blackford, Amanda
Marr, Kieren A.
Treadway, Suzanne
Ostrander, Darin
Nussenblatt, Veronique
Karp, Judith
TI Epidemiology, outcomes, and risk factors of invasive fungal infections
in adult patients with acute myelogenous leukemia after induction
chemotherapy
SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
LA English
DT Article
DE Invasive fungal infections; Acute myeloid leukemia; Epidemiology; Risk
factors; Survival
ID ACUTE MYELOID-LEUKEMIA; NEUTROPENIC PATIENTS; HEMATOLOGIC MALIGNANCIES;
PULMONARY ASPERGILLOSIS; FLUCONAZOLE PROPHYLAXIS; RESPIRATORY-TRACT;
CONTROLLED-TRIAL; DOUBLE-BLIND; POSACONAZOLE; DIAGNOSIS
AB This is a retrospective, single-center study of adult patients with newly diagnosed acute myelogenous leukemia (AML), who received intensive induction timed sequential chemotherapy from 1/2005 to 6/2010. Among 254 consecutive AML patients, 123 (48.4%) developed an invasive fungal infection (IFI): 14 (5.5%) patients with invasive candidiasis (IC) and 108 (42.5%) patients with invasive mould infections (IMI). Among 108 IMI identified, 4 (3.7%) were proven, 1 (0.9%) probable, and 103 (95.4%) were possible, using current definitions. Overall, 6-month mortality was 23.7% (27/114) and 20.6% (26/126) for patients with and without an IFI, respectively. Older age (>= 50 years; hazard ratio [HR] 2.5, P < 0.001), female gender (HR: 1.7, P = 0.006), and baseline renal and/or liver dysfunction (HR: 2.4, P < 0.001) were the strongest mortality predictors. We report relatively low rates of IC despite lack of routine primary antifungal prophylaxis, albeit associated with poor long-term survival. High rates of IMI, the vast majority with a possible diagnosis, were observed. Host-related variables (demographics and baseline organ dysfunction) were identified as the most significant risk factors for IFI and mortality predictors in this series. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Neofytos, Dionissios; Lu, Kit; Marr, Kieren A.; Treadway, Suzanne; Ostrander, Darin; Nussenblatt, Veronique] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Lu, Kit] NIH, Dept Oncol, Bethesda, MD 20892 USA.
[Hatfield-Seung, Amy] Johns Hopkins Univ Hosp, Dept Pharm, Baltimore, MD 21287 USA.
[Blackford, Amanda; Marr, Kieren A.; Karp, Judith] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
RP Neofytos, D (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
EM dneofyt1@jhmi.edu
FU Pfizer; Astellas; Merck; Pfizer [WS297422]; National Cancer Institute
[2P30-06973-48]; National Institute of Health [AI85118]
FX D.N. has received research grants from Pfizer and has served on advisory
boards for Roche. K.A.M. has received grant support from Astellas,
Merck, and Pfizer, and has served on advisory boards or as a consultant
for Astellas. Basilea, Merck, and Pfizer. J.K. has received grants from
Pfizer. All other authors: no conflicts of interest.; The study was
supported, in part, by a grant from Pfizer (WS297422), a National Cancer
Institute grant (2P30-06973-48), and a National Institute of Health K24
grant (AI85118).
NR 22
TC 20
Z9 21
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0732-8893
J9 DIAGN MICR INFEC DIS
JI Diagn. Microbiol. Infect. Dis.
PD FEB
PY 2013
VL 75
IS 2
BP 144
EP 149
DI 10.1016/j.diagmicrobio.2012.10.001
PG 6
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA 088SV
UT WOS:000314858300007
PM 23142166
ER
PT J
AU Ratnayaka, K
Faranesh, AZ
Hansen, MS
Stine, AM
Halabi, M
Barbash, IM
Schenke, WH
Wright, VJ
Grant, LP
Kellman, P
Kocaturk, O
Lederman, RJ
AF Ratnayaka, Kanishka
Faranesh, Anthony Z.
Hansen, Michael S.
Stine, Annette M.
Halabi, Majdi
Barbash, Israel M.
Schenke, William H.
Wright, Victor J.
Grant, Laurie P.
Kellman, Peter
Kocaturk, Ozgur
Lederman, Robert J.
TI Real-time MRI-guided right heart catheterization in adults using passive
catheters
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE Catheterization; Magnetic resonance imaging; Interventional
cardiovascular MRI; Pulmonary artery
ID IN-VIVO VALIDATION; CARDIAC-CATHETERIZATION; PULMONARY-HYPERTENSION;
CLINICAL-APPLICATION; RESONANCE; INTERVENTIONS; CHILDREN; DISEASE;
CLOSURE
AB Real-time MRI creates images with superb tissue contrast that may enable radiation-free catheterization. Simple procedures are the first step towards novel interventional procedures. We aim to perform comprehensive transfemoral diagnostic right heart catheterization in an unselected cohort of patients entirely using MRI guidance.
We performed X-ray and MRI-guided transfemoral right heart catheterization in consecutive patients undergoing clinical cardiac catheterization. We sampled both cavae and both pulmonary arteries. We compared success rate, time to perform key steps, and catheter visibility among X-ray and MRI procedures using air-filled or gadolinium-filled balloon-tipped catheters. Sixteen subjects (four with shunt, nine with coronary artery disease, three with other) underwent paired X-ray and MRI catheterization. Complete guidewire-free catheterization was possible in 15 of 16 under both. MRI using gadolinium-filled balloons was at least as successful as X-ray in all procedure steps, more successful than MRI using air-filled balloons, and better than both in entering the left pulmonary artery. Total catheterization time and individual procedure steps required approximately the same amount of time irrespective of image guidance modality. Catheter conspicuity was best under X-ray and next-best using gadolinium-filled MRI balloons.
In this early experience, comprehensive transfemoral right heart catheterization appears feasible using only MRI for imaging guidance. Gadolinium-filled balloon catheters were more conspicuous than air-filled ones. Further workflow and device enhancement are necessary for clinical adoption.
C1 [Ratnayaka, Kanishka; Faranesh, Anthony Z.; Hansen, Michael S.; Stine, Annette M.; Halabi, Majdi; Barbash, Israel M.; Schenke, William H.; Wright, Victor J.; Grant, Laurie P.; Kellman, Peter; Kocaturk, Ozgur; Lederman, Robert J.] NHLBI, Div Intramural Res, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Ratnayaka, Kanishka] Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA.
RP Lederman, RJ (reprint author), NHLBI, Div Intramural Res, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room 2C713,MSC 1538, Bethesda, MD 20892 USA.
EM lederman@nih.gov
RI Hansen, Michael/J-5391-2015; Kocaturk, Ozgur/A-1419-2016
OI Hansen, Michael/0000-0002-8087-8731;
FU Division of Intramural Research, National Heart Lung and Blood
Institute, National Institutes of Health, USA [Z01-HL005062-08,
Z01-HL006039-01, Z01-HL006041-01, Z01-HL006061-01]
FX This work was supported by the Division of Intramural Research
(Z01-HL005062-08, Z01-HL006039-01, Z01-HL006041-01, and
Z01-HL006061-01), National Heart Lung and Blood Institute, National
Institutes of Health, USA.
NR 17
TC 23
Z9 23
U1 0
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD FEB
PY 2013
VL 34
IS 5
BP 380
EP 389
DI 10.1093/eurheartj/ehs189
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 089EW
UT WOS:000314893900011
PM 22855740
ER
PT J
AU Myers, RC
King, RG
Carter, RH
Justement, LB
AF Myers, Riley C.
King, R. Glenn
Carter, Robert H.
Justement, Louis B.
TI Lymphotoxin alpha(1)beta(2) expression on B cells is required for
follicular dendritic cell activation during the germinal center response
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE CD19; Follicular dendritic cell; Germinal center; Membrane lymphotoxin
ID TUMOR-NECROSIS-FACTOR; SECONDARY LYMPHOID-TISSUES; FC-GAMMA-RII;
COMPLEMENT RECEPTORS; ADHESION MOLECULE-1; SPLENIC FOLLICLES;
ALPHA-DEFICIENT; GENE-EXPRESSION; MARGINAL SINUS; STROMAL CELLS
AB CD19-deficient mice were used as a model to study follicular dendritic cell (FDC) activation because these mice have normal numbers of FDC-containing primary follicles, but lack the ability to activate FDCs or form GCs. It was hypothesized that CD19 expression is necessary for B-cell activation and upregulation of membrane lymphotoxin (mLT) expression, which promotes FDC activation. Using VCAM-1 and FcRII/III as FDC activation markers, it was determined that the adoptive transfer of CD19+ wild-type B cells into CD19-deficient hosts rescued GC formation and FDC activation, demonstrating that CD19 expression on B cells is required for FDC activation. In contrast, CD19+ donor B cells lacking mLT were unable to induce VCAM-1 expression on FDCs, furthermore FcRII/III upregulation was impaired in FDCs stimulated with mLT-deficient B cells. VCAM-1 expression on FDCs, but not FcRII/III, was rescued when CD19-deficient B cells expressing transgenic mLT were cotransferred into recipient mice with CD19+, mLT-deficient B cells, suggesting that FDC activation requires the CD19-dependent upregulation of mLT on activated B cells. Collectively, these data demonstrate that activated B cells are responsible for the initiation of FDC activation resulting in a microenvironment supportive of GC development and maintenance.
C1 [Myers, Riley C.; King, R. Glenn; Justement, Louis B.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
[Carter, Robert H.] NIAMSD, Bethesda, MD 20892 USA.
RP Justement, LB (reprint author), Univ Alabama Birmingham, Dept Microbiol, 1825 Univ Blvd,Room 502 SHEL, Birmingham, AL 35294 USA.
EM lbjust@uab.edu
OI Justement, Louis/0000-0001-7058-867X
FU National Institutes of Health [AI042265-13]
FX We would like to thank Jason G. Cyster for kappa LT alpha-Tg mice,
Sergei A. Nedospasov and David D. Chaplin for LT beta floxed mice,
Jeffery Browning for anti-LT beta, the UAB High Resolution Imaging
facility, and the UAB Arthritis and Musculoskeletal Flow Core facility.
This work was supported by the National Institutes of Health (grant
AI042265-13 to L. B. Justement).
NR 53
TC 8
Z9 8
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD FEB
PY 2013
VL 43
IS 2
BP 348
EP 359
DI 10.1002/eji.201242471
PG 12
WC Immunology
SC Immunology
GA 091LN
UT WOS:000315051100009
PM 23112125
ER
PT J
AU Leung, WH
Tarasenko, T
Biesova, Z
Kole, H
Walsh, ER
Bolland, S
AF Leung, Wai-Hang
Tarasenko, Tatiana
Biesova, Zuzana
Kole, Hemanta
Walsh, Elizabeth R.
Bolland, Silvia
TI Aberrant antibody affinity selection in SHIP-deficient B cells
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Affinity maturation; B cell; Negative selection; SHIP
ID INOSITOL PHOSPHATASE SHIP; CLASS-SWITCH RECOMBINATION; 5'-PHOSPHATASE
SHIP; NEGATIVE REGULATOR; 5-PHOSPHATASE SHIP; SOMATIC MUTATION; MARGINAL
ZONE; IN-VIVO; RECEPTOR; ACTIVATION
AB The strength of the Ag receptor signal influences development and negative selection of B cells, and it might also affect B-cell survival and selection in the GC. Here, we have used mice with B-cell-specific deletion of the 5-inositol phosphatase SHIP as a model to study affinity selection in cells that are hyperresponsive to Ag and cytokine receptor stimulation. In the absence of SHIP, B cells have lower thresholds for Ag- and interferon (IFN)-induced activation, resulting in augmented negative selection in the BM and enhanced B-cell maturation in the periphery. Despite a tendency to spontaneously downregulate surface IgM expression, SHIP deficiency does not alter anergy induction in response to soluble hen-egg lysozyme Ag in the MDA4 transgenic model. SHIP-deficient B cells spontaneously produce isotype-switched antibodies; however, they are poor responders in immunization and infection models. While SHIP-deficient B cells form GCs and undergo mutation, they are not properly selected for high-affinity antibodies. These results illustrate the importance of negative regulation of B-cell responses, as lower thresholds for B-cell activation promote survival of low affinity and deleterious receptors to the detriment of optimal Ab affinity maturation.
C1 [Leung, Wai-Hang; Tarasenko, Tatiana; Biesova, Zuzana; Kole, Hemanta; Walsh, Elizabeth R.; Bolland, Silvia] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Bolland, S (reprint author), 12441 Parklawn Dr, Rockville, MD 20852 USA.
EM sbolland@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX We thank Drs. Jack R. Bennink and Jonathan W. Yewdell (NIAID) for
providing the VSV-IND, Bethany Scott for managing the mouse work. This
work was supported by the Intramural Research Program of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 48
TC 9
Z9 9
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD FEB
PY 2013
VL 43
IS 2
BP 371
EP 381
DI 10.1002/eji.201242809
PG 11
WC Immunology
SC Immunology
GA 091LN
UT WOS:000315051100011
PM 23135975
ER
PT J
AU Pagan, AJ
Peters, NC
Debrabant, A
Ribeiro-Gomes, F
Pepper, M
Karp, CL
Jenkins, MK
Sacks, DL
AF Pagan, Antonio J.
Peters, Nathan C.
Debrabant, Alain
Ribeiro-Gomes, Flavia
Pepper, Marion
Karp, Christopher L.
Jenkins, Marc K.
Sacks, David L.
TI Tracking antigen-specific CD4+T cells throughout the course of chronic
Leishmania major infection in resistant mice
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE CD4+T cells; IFN-; IL-10; Leishmania major; Tetramer
ID REGULATORY T-CELLS; TRANSCRIPTION FACTOR; IN-VIVO; C-MAF; MEMORY; NAIVE;
EXPANSION; CD8(+); PERSISTENCE; PROTECTION
AB Primary Leishmania major infection typically produces cutaneous lesions that not only heal but also harbor persistent parasites. While the opposing roles of CD4+ T-cell-derived IFN- and IL-10 in promoting parasite killing and persistence have been well established, how these responses develop from naive precursors has not been directly monitored throughout the course of infection. We used peptide:Major Histocompatibility Complex class II (pMHCII) tetramers to investigate the endogenous, parasite-specific primary CD4+ T-cell response to L. major in mice resistant to infection. Maximal frequencies of IFN-+ CD4+ T cells were observed in the spleen and infected ears within a month after infection and were maintained into the chronic phase. In contrast, peak frequencies of IL-10+ CD4+ T cells emerged within 2 weeks of infection, persisted into the chronic phase, and accumulated in the infected ears but not the spleen, via a process that depended on local antigen presentation. T helper type-1 (Th1) cells, not Foxp3+ regulatory T cells, were the chief producers of IL-10 and were not exhausted. Therefore, tracking antigen-specific CD4+ T cells revealed that IL-10 production by Th1 cells is not due to persistent T-cell antigen receptor stimulation, but rather driven by early antigen encounter at the site of infection.
C1 [Pagan, Antonio J.; Pepper, Marion; Jenkins, Marc K.] Univ Minnesota, Sch Med, Dept Microbiol, Ctr Immunol, Minneapolis, MN 55455 USA.
[Peters, Nathan C.; Ribeiro-Gomes, Flavia; Sacks, David L.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Debrabant, Alain] US FDA, Div Emerging & Transfus Transmitted Dis, OBRR, CBER, Bethesda, MD 20014 USA.
[Karp, Christopher L.] Cincinnati Childrens Hosp Res Fdn, Div Mol Immunol, Div Infect Dis, Cincinnati, OH USA.
[Karp, Christopher L.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
RP Sacks, DL (reprint author), NIAID, Parasit Dis Lab, Bldg 4,Room B1-12,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA.
EM dsacks@nih.gov
RI Jenkins, Marc/G-1063-2012; Ribeiro-Gomes, Flavia/F-7609-2015;
OI Jenkins, Marc/0000-0001-8009-7655; Karp, Christopher/0000-0002-0832-2659
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health; US National Institutes of Health [R37 AI027998,
R01 AI039614, R01 AI066016, T32 AI07313, T32 CA9138]; Minnesota Medical
Foundation
FX We thank Kim Beacht, J. Walter, and R. Speier for expert technical
assistance. This work was supported in part by the Intramural Research
Program of the National Institute of Allergy and Infectious Diseases,
National Institutes of Health, and by grants from the US National
Institutes of Health, R37 AI027998, R01 AI039614, and R01 AI066016 (M.
K. J.), T32 AI07313 (A. J. P.), and T32 CA9138 (M. P.), and a Frieda M.
Kunze Fellowship from the Minnesota Medical Foundation (A.J.P.).
NR 56
TC 15
Z9 15
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD FEB
PY 2013
VL 43
IS 2
BP 427
EP 438
DI 10.1002/eji.201242715
PG 12
WC Immunology
SC Immunology
GA 091LN
UT WOS:000315051100016
PM 23109292
ER
PT J
AU Groelz, D
Sobin, L
Branton, P
Compton, C
Wyrich, R
Rainen, L
AF Groelz, Daniel
Sobin, Leslie
Branton, Philip
Compton, Carolyn
Wyrich, Ralf
Rainen, Lynne
TI Non-formalin fixative versus formalin-fixed tissue: A comparison of
histology and RNA quality
SO EXPERIMENTAL AND MOLECULAR PATHOLOGY
LA English
DT Article
DE PAXgene Tissue; RNA; RNA integrity score; H&E histology; Quantitative RT
PCR
ID PARAFFIN-EMBEDDED TISSUE; PROTEOMIC ANALYSIS; NUCLEIC-ACIDS; INTEGRITY;
SAMPLES; OPTIMIZATION; PRESERVATION; RECOVERY; CANCERS; NUMBER
AB Preanalytical handling of tissue samples can influence bioanalyte quality and ultimately outcome of analytical results. The aim of this study was to compare RNA quality, performance in real time RT PCR and histology of formalin-fixed tissue to that of tissue fixed and stabilized with a formalin-free fixative, the PAXgene Tissue System (PAXgene), in an animal model under highly controlled preanalytical conditions. Samples of rat liver, kidney, spleen, intestine, lung, heart muscle, brain, and stomach tissue were either fixed in formalin or fixed in PAXgene or fresh frozen in liquid nitrogen. RNA was extracted from all samples, examined for integrity in microcapillary electrophoresis, and used in a series of quantitative RT PCR assays with increasing amplicon length. Histology of paraffin-embedded samples was determined by staining with hematoxylin and eosin.
Histology of all formalin-fixed and PAXgene fixed samples was comparable. RNA with acceptable integrity scores could be isolated from all embedded tissues, 4.0 to 7.2 for formalin and 6.4 to 7.7 for PAXgene, as compared to 8.0 to 9.2 for fresh frozen samples. While RNA with acceptable RINs (RNA integrity number) could be isolated from formalin-fixed samples, in microcapillary electrophoresis this RNA separated with a slower migration rate and displayed diffuse, less focused peaks for ribosomal RNA as compared to RNA from frozen or PAXgene fixed samples. Furthermore, RNA from formalin-fixed tissues exhibited inhibition in quantitative RI PCR assays which increased with increasing amplicon length, while RNA from PAXgene fixed samples did not show such inhibition.
In conclusion, our results demonstrate that excluding other preanalytical factors, PAXgene Tissue System preserves histology similarly to formalin, but unlike formalin, does not chemically modify RNA. RNA purified from PAXgene fixed tissues is of high integrity and performs as well as RNA from fresh frozen tissue in RI PCR regardless of amplicon length. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Groelz, Daniel; Wyrich, Ralf] Qiagen GmbH, Res & Dev, D-40724 Hilden, Germany.
[Rainen, Lynne] PreAnalytiX GmbH, Res & Dev, Franklin Lakes, NJ USA.
[Branton, Philip; Compton, Carolyn] NCI, Off Biorepositories & Biospecimen Res, NIH, Bethesda, MD 20892 USA.
[Sobin, Leslie] NCI, Frederick Natl Lab Canc Res, Rockville, MD USA.
[Compton, Carolyn] Crit Path Inst C Path, Tucson, AZ USA.
RP Groelz, D (reprint author), QIAGEN GmbH, QIAGEN Str 1, D-40724 Hilden, Germany.
EM Daniel.groelz@qiagen.com; leslie.sobin@nih.gov; philip.branton@nih.gov;
CCompton@c-path.org; Ralf.Wyrich@qiagen.com; Lynne_Rainen@bd.com
FU European Union [222916]
FX The authors wish to thank Nadine Dettmann, Isabell Blassnig and Evelyn
Traenert for their technical assistance. The research leading to these
results has received funding from the European Union Seventh Framework
Programme [FP7/2007-2013] under grant agreement no. 222916.
NR 28
TC 23
Z9 24
U1 1
U2 28
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4800
J9 EXP MOL PATHOL
JI Exp. Mol. Pathol.
PD FEB
PY 2013
VL 94
IS 1
BP 188
EP 194
DI 10.1016/j.yexmp.2012.07.002
PG 7
WC Pathology
SC Pathology
GA 090UW
UT WOS:000315006500028
PM 22814231
ER
PT J
AU Espey, MG
AF Espey, Michael Graham
TI Role of oxygen gradients in shaping redox relationships between the
human intestine and its microbiota
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Review
DE Gut; Hydrogen peroxide; Hydrogen sulfide; Innate immunity; Microbiome;
Nitric oxide; NADPH oxidase; NOX; Oxygen; Free radicals
ID SULFATE-REDUCING BACTERIA; INFLAMMATORY-BOWEL-DISEASE; NITRIC-OXIDE
SYNTHASES; COLON EPITHELIAL-CELLS; HUMAN GUT MICROBIOME;
ULCERATIVE-COLITIS; HYDROGEN-SULFIDE; REACTIVE OXYGEN;
GASTROINTESTINAL-TRACT; ESCHERICHIA-COLI
AB The unique anatomy and physiology of the intestine in conjunction with its microbial content create the steepest oxygen gradients in the body, which plunge to near anoxia at the luminal midpoint. Far from static, intestinal oxygen gradients ebb and flow with every meal. This in turn governs the redox effectors nitric oxide, hydrogen sulfide, and reactive oxygen species of both host and bacterial origin. This review illustrates how the intestine and microbes utilize oxygen gradients as a backdrop for mechanistically shaping redox relationships and a functional coexistence. Published by Elsevier Inc.
C1 NIDDKD, Off Sci Director, NIH, Bethesda, MD 20892 USA.
RP Espey, MG (reprint author), NIDDKD, Off Sci Director, NIH, Bethesda, MD 20892 USA.
EM SP@nih.gov
FU Intramural Research Program of the NIDDK, NIH
FX This research was supported by the Intramural Research Program of the
NIDDK, NIH.
NR 160
TC 54
Z9 55
U1 8
U2 72
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD FEB
PY 2013
VL 55
BP 130
EP 140
DI 10.1016/j.freeradbiomed.2012.10.554
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 090WB
UT WOS:000315009600015
PM 23127782
ER
PT J
AU Wong, GS
Habibollahi, P
Heidari, P
Lee, JS
Klein-Szanto, AJ
Waldron, TJ
Gimotty, P
Nakagawa, H
Taylor, PR
Wang, TC
Mahmood, U
Rustgi, AK
AF Wong, Gabrielle S.
Habibollahi, Peiman
Heidari, Pedram
Lee, Ju-Seog
Klein-Szanto, Andres J.
Waldron, Todd J.
Gimotty, Phyllis
Nakagawa, Hiroshi
Taylor, Philip R.
Wang, Timothy C.
Mahmood, Umar
Rustgi, Anil K.
TI Optical Imaging of Periostin Enables Early Endoscopic Detection and
Characterization of Esophageal Cancer in Mice
SO GASTROENTEROLOGY
LA English
DT Article
DE Mouse Model; Esophageal Cancer; Extracellular; Matrix; POSTN; Tumor
Microenvironment
ID TUMOR MICROENVIRONMENT; CELL; IDENTIFICATION; INVASION
AB Imaging strategies that detect early stage esophageal squamous cell carcinoma (ESCC) could improve clinical outcomes, when combined with endoscopic approaches. Periostin is an integrin-binding protein that is important in the tumor microenvironment. We created a fluorescent-labeled antibody that recognizes periostin and binds specifically to ESCC xenograft tumors in mice. In L2-cre; p120ctnLoxP/LoxP mice, which develop squamous cell cancers that resemble human ESCC, we visualized the probe in preneoplastic and neoplastic esophageal lesions using near-infrared fluorescent imaging with upper-gastrointestinal endoscopy. Periostin might be a biomarker of the esophageal tumor microenvironment that can be used to detect preneoplastic lesions.
C1 [Wong, Gabrielle S.; Waldron, Todd J.; Nakagawa, Hiroshi; Rustgi, Anil K.] Univ Penn, Perelman Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA.
[Wong, Gabrielle S.; Waldron, Todd J.; Nakagawa, Hiroshi; Rustgi, Anil K.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Wong, Gabrielle S.; Waldron, Todd J.; Gimotty, Phyllis; Nakagawa, Hiroshi; Rustgi, Anil K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Gimotty, Phyllis] Univ Penn, Ctr Clin Epidemiol & Biostat, Div Biostat, Philadelphia, PA 19104 USA.
[Rustgi, Anil K.] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
[Habibollahi, Peiman; Heidari, Pedram; Mahmood, Umar] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA.
[Lee, Ju-Seog] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
[Klein-Szanto, Andres J.] Fox Chase Canc Ctr, Dept Pathol & Canc Biol, Philadelphia, PA 19111 USA.
[Taylor, Philip R.] NCI, Genet Epidemiol Branch, DCEG, NIH, Bethesda, MD 20892 USA.
[Wang, Timothy C.] Columbia Univ, Med Ctr, Dept Med, Div Digest & Liver Dis, New York, NY USA.
[Wang, Timothy C.] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY USA.
RP Rustgi, AK (reprint author), Univ Penn, 951 BRB,421 Curie Blvd, Philadelphia, PA 19104 USA.
EM anil2@mail.med.upenn.edu
FU National Institutes of Health/NCI [P01-CA098101, U01-CA14305603];
National Institutes of Health [T32-CA115299, F32-CA162719]; National
Institutes of Health/NIDDK [T32-DK007066]; National Institutes of
Health/NIDDK Center for Molecular Studies in Digestive and Liver
Diseases [P30DK050306]; American Cancer Society [RP-10-033-01-CCE];
Intramural Research Program of the US National Institutes of Health,
NCI; Division of Cancer Epidemiology and Genetics
FX Supported by National Institutes of Health/NCI grant P01-CA098101,
National Institutes of Health grant T32-CA115299, National Institutes of
Health/NIDDK (T32-DK007066), National Institutes of Health
(F32-CA162719), National Institutes of Health/NCI grant U01-CA14305603,
National Institutes of Health/NIDDK Center for Molecular Studies in
Digestive and Liver Diseases (P30DK050306), American Cancer Society
(RP-10-033-01-CCE), and the Intramural Research Program of the US
National Institutes of Health, NCI, and the Division of Cancer
Epidemiology and Genetics.
NR 15
TC 11
Z9 12
U1 1
U2 12
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD FEB
PY 2013
VL 144
IS 2
BP 294
EP 297
DI 10.1053/j.gastro.2012.10.030
PG 4
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 086VL
UT WOS:000314716300022
PM 23085486
ER
PT J
AU Takeda, H
Koso, H
Tessarollo, L
Copeland, NG
Jenkins, NA
AF Takeda, Haruna
Koso, Hideto
Tessarollo, Lino
Copeland, Neal G.
Jenkins, Nancy A.
TI Musashi1-CreER(T2): A new cre line for conditional mutagenesis in neural
stem cells
SO GENESIS
LA English
DT Article
DE Msi1; NSCs; SVZ; olfactory epithelium; knock-in mice
ID RNA-BINDING PROTEIN; ADULT NEUROGENESIS; RECOMBINASE ACTIVITY;
IDENTIFICATION; EXPRESSION; PROGENITOR; MUSASHI-1; MARKER
AB The RNA-binding protein Musashi1 (Msi1) is one of two mammalian homologues of DrosophilaMusashi, which is required for the asymmetric cell division of sensory organ precursor cells. In the mouse central nervous system (CNS), Msi1 is preferentially expressed in mitotically active progenitor cells in the ventricular zone (VZ) of the neural tube during embryonic development and in the subventricular zone (SVZ) of the postnatal brain. Previous studies showed that cells in the SVZ can contribute to long-term neurogenesis in the olfactory bulb (OB), but it remains unclear whether Msi1-expressing cells have self-renewing potential and can contribute to neurogenesis in the adult. Here, we describe the generation of Msi1-CreERT2 knock-in mice and show by cell lineage tracing that Msi1-CreERT2-expressing cells mark neural stem cells (NSCs) in both the embryonic and adult brain. Msi1-CreERT2 mice thus represent a new tool in our arsenal for genetically manipulating NSCs, which will be essential for understanding the molecular mechanisms underlying neural development. genesis, 51:128134, 2013. (c) 2012 Wiley Periodicals, Inc.
C1 [Takeda, Haruna; Koso, Hideto; Copeland, Neal G.; Jenkins, Nancy A.] Agcy Sci Technol & Res, Div Genom & Genet, Inst Mol & Cell Biol, Singapore, Singapore.
[Takeda, Haruna] Univ Tokyo, Dept Microbiol, Grad Sch Med, Tokyo, Japan.
[Takeda, Haruna] Univ Tokyo, Fac Med, Tokyo 113, Japan.
[Koso, Hideto] Univ Tokyo, Inst Med Sci, Div Mol & Dev Biol, Tokyo, Japan.
[Tessarollo, Lino] NCI, Neural Dev Grp, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Copeland, Neal G.; Jenkins, Nancy A.] Methodist Hosp, Canc Res Program, Res Inst, Houston, TX 77030 USA.
RP Jenkins, NA (reprint author), Agcy Sci Technol & Res, Div Genom & Genet, Inst Mol & Cell Biol, Singapore, Singapore.
EM njenkins2@tmhs.org
RI ASTAR, IMCB/E-2320-2012
FU Agency for Science, Technology and Research (A-STAR), Singapore; Cancer
Prevention Research Institute of Texas; NCI, Center for Cancer Research,
NIH
FX Contract grant sponsors: Agency for Science, Technology and Research
(A-STAR), Singapore; Cancer Prevention Research Institute of Texas.; We
thank Keith Rogers, Susan M. Rogers, and Vanessa Shiyun Tay for
technical support. N.A.J. and N.G.C. are both CPRIT Scholars in Cancer
Research. L.T. was supported by the Intramural Research Program of the
NCI, Center for Cancer Research, NIH. The authors declare no conflict of
interests.
NR 26
TC 6
Z9 6
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1526-954X
J9 GENESIS
JI Genesis
PD FEB
PY 2013
VL 51
IS 2
BP 128
EP 134
DI 10.1002/dvg.22357
PG 7
WC Developmental Biology; Genetics & Heredity
SC Developmental Biology; Genetics & Heredity
GA 092DE
UT WOS:000315098300006
PM 23132814
ER
PT J
AU Schoenebeck, JJ
Ostrander, EA
AF Schoenebeck, Jeffrey J.
Ostrander, Elaine A.
TI The Genetics of Canine Skull Shape Variation
SO GENETICS
LA English
DT Editorial Material
ID RADIATION HYBRID MAP; DOMESTIC DOG; LINKAGE DISEQUILIBRIUM; GENOME;
ASSOCIATION; TCOF1; CRANIOSYNOSTOSIS; CHROMOSOME; MULTIPLE; SEQUENCE
AB A dog's craniofacial diversity is the result of continual human intervention in natural selection, a process that began tens of thousands of years ago. To date, we know little of the genetic underpinnings and developmental mechanisms that make dog skulls so morphologically plastic. In this Perspectives, we discuss the origins of dog skull shapes in terms of history and biology and highlight recent advances in understanding the genetics of canine skull shapes. Of particular interest are those molecular genetic changes that are associated with the development of distinct breeds.
C1 [Schoenebeck, Jeffrey J.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Ostrander, EA (reprint author), NHGRI, NIH, Bldg 50,Room 5351, Bethesda, MD 20892 USA.
EM eostrand@mail.nih.gov
OI Ostrander, Elaine/0000-0001-6075-9738
FU Intramural NIH HHS
NR 62
TC 17
Z9 17
U1 8
U2 109
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
J9 GENETICS
JI Genetics
PD FEB
PY 2013
VL 193
IS 2
BP 317
EP +
DI 10.1534/genetics.112.145284
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 088GH
UT WOS:000314821300001
PM 23396475
ER
PT J
AU Wesolowska, N
Rong, YS
AF Wesolowska, Natalia
Rong, Yikang S.
TI Long-Range Targeted Manipulation of the Drosophila Genome by
Site-Specific Integration and Recombinational Resolution
SO GENETICS
LA English
DT Article
ID HOMOLOGOUS RECOMBINATION; MELANOGASTER; REPAIR; REPLACEMENT; INSERTION;
PHI-C31; GENES; YEAST
AB Significant advances in genomics underscore the importance of targeted mutagenesis for gene function analysis. Here we have developed a scheme for long-range targeted manipulation of genes in the Drosophila genome. Utilizing an attP attachment site for the phiC31 integrase previously targeted to the nbs gene, we integrated an 80-kb genomic fragment at its endogenous locus to generate a tandem duplication of the region. We achieved reduction to a single copy by inducing recombination via a site-specific DNA break. We report that, despite the large size of the DNA fragment, both plasmid integration and duplication reduction can be accomplished efficiently. Importantly, the integrating genomic fragment can serve as a venue for introducing targeted modifications to the entire region. We successfully introduced a new attachment site 70 kb from the existing attP using this two-step scheme, making a new region susceptible to targeted mutagenesis. By experimenting with different placements of the future DNA break site in the integrating vector, we established a vector configuration that facilitates the recovery of desired modifications. We also show that reduction events can occur efficiently through unequal meiotic crossing over between the large duplications. Based on our results, we suggest that a collection of 1200 lines with attachment sites inserted every 140 kb throughout the genome would render all Drosophila genes amenable to targeted mutagenesis. Excitingly, all of the components involved are likely functional in other eukaryotes, making our scheme for long-range targeted manipulation readily applicable to other systems.
C1 [Wesolowska, Natalia; Rong, Yikang S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Wesolowska, Natalia] Johns Hopkins Univ, Natl Inst Hlth Grad Partnership Program, Bethesda, MD 20892 USA.
RP Rong, YS (reprint author), NIH, Bldg 37,Room 6056,37 Convent Dr, Bethesda, MD 20892 USA.
EM rongy@mail.nih.gov
FU Intramural Program of the National Cancer Institute
FX We are grateful to Flavia Amariei for aiding us with screening for
spontaneous reductions and to Jemima Barrowman for her assistance in
editing the manuscript. Research in our laboratory is supported by the
Intramural Program of the National Cancer Institute.
NR 25
TC 6
Z9 6
U1 1
U2 15
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
J9 GENETICS
JI Genetics
PD FEB
PY 2013
VL 193
IS 2
BP 411
EP +
DI 10.1534/genetics.112.145631
PG 19
WC Genetics & Heredity
SC Genetics & Heredity
GA 088GH
UT WOS:000314821300007
PM 23150601
ER
PT J
AU Biesecker, LG
AF Biesecker, Leslie G.
TI Secondary variants and human subjects research
SO GENETICS IN MEDICINE
LA English
DT Letter
C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
RP Biesecker, LG (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM lesb@mail.nih.gov
FU Intramural NIH HHS [ZIA HG200359-05]
NR 1
TC 5
Z9 5
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD FEB
PY 2013
VL 15
IS 2
BP 157
EP 157
DI 10.1038/gim.2012.161
PG 1
WC Genetics & Heredity
SC Genetics & Heredity
GA 087WK
UT WOS:000314794900011
PM 23386183
ER
PT J
AU Holland, SM
AF Holland, Steven M.
TI Chronic Granulomatous Disease
SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Chronic granulomatous disease; Gene defects; NADPH oxidase; Immune
defect; Inflammatory bowel disease
ID DISCOID LUPUS-ERYTHEMATOSUS; INTERFERON-GAMMA THERAPY; INVASIVE
ASPERGILLOSIS; CLINICAL-FEATURES; GRANULIBACTER-BETHESDENSIS; INCREASED
SUSCEPTIBILITY; HEMATOPOIETIC ALLOGRAFT; NEOSARTORYA-UDAGAWAE; EUROPEAN
EXPERIENCE; NADPH OXIDASE
AB Chronic granulomatous disease (CGD) is a paradigm for nonlymphoid primary immune defects, and has guided elucidation of oxygen metabolism in the phagocyte, vasculature, and brain. It has been in the forefront of the development of antimicrobial prophylaxis before the advent of advanced HIV and before its routine use in neutropenia. It has been an attractive target for gene therapy and bone marrow transplantation for nonmalignant diseases. Therefore, CGD is worthy of attention for its historical interest and because it is a disease for which expert management is imperative.
C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Holland, SM (reprint author), NIAID, Lab Clin Infect Dis, NIH, CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA.
EM smh@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 71
TC 55
Z9 58
U1 0
U2 13
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8588
J9 HEMATOL ONCOL CLIN N
JI Hematol. Oncol. Clin. North Am.
PD FEB
PY 2013
VL 27
IS 1
BP 89
EP +
DI 10.1016/j.hoc.2012.11.002
PG 12
WC Oncology; Hematology
SC Oncology; Hematology
GA 090TC
UT WOS:000315001900007
PM 23351990
ER
EF