= 18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1: 1 ratio, with random permuted block design [block size 2, 4, or 6], stratified by clinical site) to medical management with interventional therapy (ie, neurosurgery, embolisation, or stereotactic radiotherapy, alone or in combination) or medical management alone (ie, pharmacological therapy for neurological symptoms as needed). Patients, clinicians, and investigators are aware of treatment assignment. The primary outcome is time to the composite endpoint of death or symptomatic stroke; the primary analysis is by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389181.
Findings Randomisation was started on April 4, 2007, and was stopped on April 15, 2013, when a data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4.10, exceeding the prespecified stopping boundary value of 2.87). At this point, outcome data were available for 223 patients (mean follow-up 33.3 months [SD 19.7]), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10.1%) patients in the medical management group compared with 35 (30.7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0.27, 95% CI 0.14-0.54). No harms were identified, other than a higher number of strokes (45 vs 12, p<0.0001) and neurological deficits unrelated to stroke (14 vs 1, p=0.0008) in patients allocated to interventional therapy compared with medical management.
Interpretation The ARUBA trial showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. The trial is continuing its observational phase to establish whether the disparities will persist over an additional 5 years of follow-up.
C1 [Mohr, J. P.; Stapf, Christian] Columbia Univ, Neurol Inst, Med Ctr, New York, NY USA.
[Parides, Michael K.; Moquete, Ellen; Overbey, Jessica R.; Moskowitz, Alan J.] Icahn Sch Med Mt Sinai, Dept Hlth Evidence & Policy, Int Ctr Hlth Outcomes & Innovat Res, New York, NY USA.
[Stapf, Christian] Univ Paris Diderot Sorbonne Paris Cite, Hop Lariboisiere, AP HP, Dept Neurol, Paris, France.
[Stapf, Christian] Univ Paris Diderot Sorbonne Paris Cite, Hop Lariboisiere, AP HP, DHU NeuroVasc, Paris, France.
[Houdart, Emmanuel] Univ Paris Diderot Sorbonne Paris Cite, Hop Lariboisiere, AP HP, Dept Neuroradiol, Paris, France.
[Vicaut, Eric] Univ Paris Diderot Sorbonne Paris Cite, Hop Lariboisiere, AP HP, Unite Rech Clin, Paris, France.
[Moy, Claudia S.] NINDS, NIH, Bethesda, MD 20892 USA.
[Salman, Rustam Al-Shahi] Univ Edinburgh, Ctr Clin Brain Sci, Div Clin Neurosci, Edinburgh, Midlothian, Scotland.
[Young, William L.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA.
[Cordonnier, Charlotte] Univ Lille Nord France, CHRU Lille, Dept Neurol, Lille, France.
[Stefani, Marco A.] Hosp Clin Porto Alegre, Dept Neurol & Neurosurg, Porto Alegre, RS, Brazil.
[Hartmann, Andreas] Charite, D-13353 Berlin, Germany.
[Hartmann, Andreas] Klinikum Frankfurt Oder, Dept Neurol, Frankfurt, Germany.
[von Kummer, Rudiger] Univ Hosp Dresden, Dept Neuroradiol, Dresden, Germany.
[Biondi, Alessandra] Univ Franche Comte, Jean Minjoz Hosp, Dept Neuroradiol & Endovasc Therapy, F-25030 Besancon, France.
[Berkefeld, Joachim] Univ Frankfurt Klinikum, Dept Neuroradiol, Frankfurt, Germany.
[Klijn, Catharina J. M.] Univ Med Ctr, Brain Ctr Rudolf Magnus, Dept Neurol & Neurosurg, Utrecht, Netherlands.
[Harkness, Kirsty] Royal Hallamshire Hosp, Dept Neurol, Sheffield S10 2JF, S Yorkshire, England.
[Libman, Richard] North Shore Long Isl Jewish Med Ctr, Dept Neurol, New Hyde Pk, NY USA.
[Barreau, Xavier] CHU Pellegrin, Dept Diagnost & Intervent Neuroimaging, Bordeaux, France.
RP Stapf, C (reprint author), Hop Lariboisiere, AP HP, Dept Neurol, Neurovasc Unit, F-75175 Paris 10, France.
EM christian.stapf@lrb.aphp.fr
RI van Dijk, J. Marc C./C-1078-2013; Klijn, C.J.M. (Karin)/E-1700-2016;
OI van Dijk, J. Marc C./0000-0002-0814-5680; Javadpour,
Mohsen/0000-0001-9836-1741; Gregson, Barbara/0000-0003-4868-9137;
Moskowitz, Alan/0000-0002-4412-9450; Touze,
Emmanuel/0000-0002-7254-2162; Al-Shahi Salman,
Rustam/0000-0002-2108-9222
FU National Institute of Neurological Diosorders and Stroke of the US
National Institutes of Health [U01NS051483, U01 NS051566]; National
Institutes of Health, National Institute of Neurological Disorders and
Stroke
FX National Institutes of Health, National Institute of Neurological
Disorders and Stroke.; This paper is dedicated in memoriam to our
colleague and friend William L Young, in recognition of his contribution
to brain arteriovenous malformations research and to the ARUBA trial. We
thank patients who participate in this trial. This trial is funded
internationally by the National Institute of Neurological Diosorders and
Stroke of the US National Institutes of Health via cooperative
agreements U01NS051483 (CCC; J.P. Mohr, PI) and U01 NS051566 (DCC; A.J.
Moskowitz, PI). No commercial funding sources have been involved. ARUBA
has been officially adopted by the UK Stroke Research Network and
endorsed by the Societe Francaise Neurovasculaire (SFNV). Initial
results have been presented at the European Stroke Conference; London,
UK; May 28-31, 2013.
NR 30
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U2 30
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD FEB 15
PY 2014
VL 383
IS 9917
BP 614
EP 621
DI 10.1016/S0140-6736(13)62302-8
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA AA5KP
UT WOS:000331137700030
PM 24268105
ER
PT J
AU Andrews, C
Gadsden, BJ
Carr, EA
Kiupel, M
AF Andrews, Caroline
Gadsden, Barbie J.
Carr, Elizabeth A.
Kiupel, Matti
TI Pathology in Practice
SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID COMPLEX ODONTOMA
C1 [Andrews, Caroline] NCI, Comparat Biomed Scientist Training Program, NIH, Bethesda, MD 20892 USA.
[Andrews, Caroline; Gadsden, Barbie J.; Kiupel, Matti] Michigan State Univ, Diagnost Ctr Populat & Anim Hlth, Lansing, MI 48910 USA.
[Carr, Elizabeth A.] Michigan State Univ, Coll Vet Med, Dept Large Anim Clin Sci, E Lansing, MI 48824 USA.
RP Andrews, C (reprint author), NCI, Comparat Biomed Scientist Training Program, NIH, Bethesda, MD 20892 USA.
EM andrewsc@dcpah.msu.edu
FU NIH HHS [T35 OD010991]
NR 7
TC 1
Z9 1
U1 1
U2 2
PU AMER VETERINARY MEDICAL ASSOC
PI SCHAUMBURG
PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA
SN 0003-1488
EI 1943-569X
J9 JAVMA-J AM VET MED A
JI JAVMA-J. Am. Vet. Med. Assoc.
PD FEB 15
PY 2014
VL 244
IS 4
BP 417
EP 419
PG 3
WC Veterinary Sciences
SC Veterinary Sciences
GA AA0UG
UT WOS:000330812300005
PM 24479454
ER
PT J
AU Xie, Y
Alexander, GM
Schwartzman, RJ
Singh, N
Torjman, MC
Goldberg, ME
Wainer, IW
Moaddel, R
AF Xie, Y.
Alexander, G. M.
Schwartzman, R. J.
Singh, N.
Torjman, M. C.
Goldberg, M. E.
Wainer, I. W.
Moaddel, R.
TI Development and validation of a sensitive LC-MS/MS method for the
determination of D-serine in human plasma
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Enantiomeric separation; Chiral derivatization; Ketamine; Complex
regional pain syndrome (CRPS)
ID PERFORMANCE-LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY;
INTRACELLULAR D-SERINE; D-AMINO ACIDS; RACEMASE; PAIN; QUANTIFICATION;
SCHIZOPHRENIA; CELLS; PC-12
AB A validated LC-MS/MS method was developed for the determination of D -Serine in human plasma. The method was fully validated for use with human plasma samples and was linear from 0.19 nmol/ml to 25 nmol/ml. The coefficient of variation was <= 5% for the high QC standards and <= 8% for the low QC standards in plasma. D -Serine and L -serine were resolved by pre-column derivatization using (R)-1-Boc-2-piperidine carbonyl chloride as the derivatizating agent. The method was used to determine the concentration of D-serine in plasma samples obtained in patients receiving a continuous 5-day intravenous infusion of (R,S)-ketamine. The changes in D-Ser levels varied in the six patients, with circulating D-Ser levels increasing as much as 35% in a patient, while decreasing 20% in a patient. While only preliminary data, the results suggests the potential importance in determining the D-Ser levels in plasma and their potential role in physiological response. Published by Elsevier B.V.
C1 [Xie, Y.; Singh, N.; Wainer, I. W.; Moaddel, R.] NIA, Lab Clin Invest, Div Intramural Res Programs, NIH, Baltimore, MD 21224 USA.
[Xie, Y.] Shanghai Jiao Tong Univ, Inst Med Sci, Dept Pharmacol, Sch Med, Shanghai 200025, Peoples R China.
[Alexander, G. M.; Schwartzman, R. J.] Drexel Univ, Dept Neurol, Coll Med, Philadelphia, PA USA.
[Torjman, M. C.; Goldberg, M. E.; Wainer, I. W.] Rowan Univ, Cooper Med Sch, Camden, NJ 08103 USA.
RP Moaddel, R (reprint author), NIA, Lab Clin Invest, Div Intramural Res Programs, NIH, Baltimore, MD 21224 USA.
EM moaddelru@mail.nih.gov
RI Singh, Nagendra/K-8966-2015
FU National Institute on Aging/NIH
FX This research was supported by the Intramural Research Program of the
National Institute on Aging/NIH.
NR 17
TC 7
Z9 7
U1 1
U2 29
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
EI 1873-264X
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD FEB 15
PY 2014
VL 89
BP 1
EP 5
DI 10.1016/j.jpba.2013.10.028
PG 5
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 300TN
UT WOS:000330487000001
PM 24247087
ER
PT J
AU Liu, MT
Wang, JN
Wu, XG
Wang, E
Baptista, D
Scott, B
Liu, P
AF Liu, Mingtao
Wang, Jennie
Wu, Xiaogang
Wang, Euphemia
Baptista, Diego
Scott, Brendan
Liu, Paul
TI HPLC method development, validation and impurity characterization for an
antitumor Hsp90 inhibitor-PU-H71 (NSC 750424)
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE PU-H71; NSC 750424; Forced degradation; HPLC validation; Stability
study; Impurity characterization
ID CANCER; PU-H71; TARGET
AB An HPLC method for the assay of the heat shock protein 90 inhibitor, PU-H71 (NSC 750424), has been developed and validated. The stress testing of PU-H71 was carried out in accordance with ICH guidelines Q1A (R2) under aqueous, acidic, alkaline, oxidative, thermolytic and photolytic conditions. The separation of PU-H71 from its impurities and degradation products was achieved within 50 min on a Mac-Mod ACE 3 C18 column (150 mm x 4.6 mm i.d., 3 mu m) with a gradient mobile phase comprising 20-95% acetonitrile in water, with 0.1% trifluroacetic acid in both phases. LC-quadrupole TOF/MS was used to obtain accurate mass data on various components as well as on their fragments for characterization of impurities and degradation products. The proposed HPLC assay method was validated for specificity, linearity (concentration range 0.1-0.3 mg/mL, r >= 0.9998), accuracy (recovery 99.7-101.1%), precision (intra-lab RSD <= 1.39%, inter-lab RSD <= 0.91%), sensitivity (LOD 0.08 mu g/mL), and ruggedness. The developed method was suitable for the assay and stability monitoring of PU-H71 drug substance. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Liu, Mingtao; Wang, Jennie; Wu, Xiaogang; Wang, Euphemia; Baptista, Diego] SRI Int, Menlo Pk, CA 94025 USA.
[Scott, Brendan] Midwest Res Inst, Kansas City, MO 64110 USA.
[Liu, Paul] NCI, Pharmaceut Resources Branch, DCTD, Bethesda, MD 20892 USA.
RP Wang, JN (reprint author), SRI Int, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA.
EM jennie.wang@sri.com
FU Developmental Therapeutics Program, Division of Cancer Treatment and
Diagnosis, National Cancer Institute, U.S. National Institutes of Health
[HHSN261200722003C, HHSN261201200028C]
FX This work was funded by Developmental Therapeutics Program, Division of
Cancer Treatment and Diagnosis, National Cancer Institute, U.S. National
Institutes of Health under Contract No. HHSN261200722003C and Contract
No. HHSN261201200028C.
NR 17
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U1 0
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
EI 1873-264X
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD FEB 15
PY 2014
VL 89
BP 34
EP 41
DI 10.1016/j.jpba.2013.10.021
PG 8
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 300TN
UT WOS:000330487000006
PM 24252723
ER
PT J
AU Shuster, LI
Moore, DR
Chen, G
Ruscello, DM
Wonderlin, WF
AF Shuster, Linda I.
Moore, Donna R.
Chen, Gang
Ruscello, Dennis M.
Wonderlin, William F.
TI Does experience in talking facilitate speech repetition?
SO NEUROIMAGE
LA English
DT Article
ID SUPPLEMENTARY MOTOR AREA; AGE-RELATED-CHANGES; CORPUS-CALLOSUM;
WHITE-MATTER; INTERHEMISPHERIC-TRANSFER; WORD RECOGNITION;
REACTION-TIME; FMRI; ACTIVATION; COMPLEXITY
AB Speech is unique among highly skilled human behaviors in its ease of acquisition by virtually all individuals who have normal hearing and cognitive ability. Vocal imitation is essential for acquiring speech, and it is an important element of social communication. The extent to which age-related changes in cognitive and motor function affect the ability to imitate speech is poorly understood. We analyzed the distributions of response times (RT) for repeating real words and pseudowords during fMRI. The average RT for older and younger participants was not different In contrast detailed analysis of RT distributions revealed age-dependent differences that were associated with changes in the time course of the BOLD response and specific patterns of regional activation. RT-dependent activity was observed in the bilateral posterior cingulate, supplementary motor area, and corpus callosum. This approach provides unique insight into the mechanisms associated with changes in speech production with aging. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Shuster, Linda I.; Moore, Donna R.; Ruscello, Dennis M.] W Virginia Univ, Dept Speech Pathol & Audiol, Morgantown, WV 26506 USA.
[Shuster, Linda I.] W Virginia Univ, Ctr Adv Imaging, Morgantown, WV 26506 USA.
[Chen, Gang] NIMH, Sci & Stat Comp Core, NIH, Bethesda, MD 20892 USA.
[Wonderlin, William F.] W Virginia Univ, Dept Biochem, Morgantown, WV 26506 USA.
RP Shuster, LI (reprint author), 515 Michigan St NE,Suite 200, Grand Rapids, MI USA.
EM shusterl@gvsu.edu; moore.2492@buckeyemail.osu.edu;
gangchen@mail.nih.gov; Dennis.Ruscello@mail.wvu.edu;
wwonderlin@hsc.wvu.edu
FU National Institute on Deafness and Other Communication Disorders of the
National Institutes of Health [R15DC011136]; Department of Radiology at
West Virginia University
FX Research reported in this publication was supported by the National
Institute on Deafness and Other Communication Disorders of the National
Institutes of Health under grant number R15DC011136 and by the
Department of Radiology at West Virginia University. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
NR 48
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U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD FEB 15
PY 2014
VL 87
BP 80
EP 88
DI 10.1016/j.neuroimage.2013.10.064
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 301TC
UT WOS:000330554000008
PM 24215974
ER
PT J
AU Lohith, TG
Zoghbi, SS
Morse, CL
Araneta, MDF
Barth, VN
Goebl, NA
Tauscher, JT
Pike, VW
Innis, RB
Fujita, M
AF Lohith, Talakad G.
Zoghbi, Sami S.
Morse, Cheryl L.
Araneta, Maria D. Ferraris
Barth, Vanessa N.
Goebl, Nancy A.
Tauscher, Johannes T.
Pike, Victor W.
Innis, Robert B.
Fujita, Masahiro
TI Retest imaging of [C-11]NOP-1A binding to nociceptin/orphanin FQ peptide
(NOP) receptors in the brain of healthy humans
SO NEUROIMAGE
LA English
DT Article
DE NOP receptors; Nociceptin; Test-retest imaging; PET; retest variability;
intraclass correlation coefficient
ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; INPUT FUNCTION; PET;
NEURORECEPTOR; RADIOLIGAND; REPRODUCIBILITY; RADIOTRACERS; C-11-NOP-1A;
VALIDATION
AB [C-11]NOP-1A is a novel high-affinity PET ligand for imaging nociceptin/orphanin FQ peptide (NOP) receptors. Here, we report reproducibility and reliability measures of binding parameter estimates for [C-11]NOP-1A binding in the brain of healthy humans.
After intravenous injection of [C-11]NOP-1A, PET scans were conducted twice on eleven healthy volunteers on the same (10/11 subjects) or different (1/11 subjects) days. Subjects underwent serial sampling of radial arterial blood to measure parent radioligand concentrations. Distribution volume (V-T; a measure of receptor density) was determined by compartmental (one- and two-tissue) modeling in large regions and by simpler regression methods (graphical Logan and bilinear MA1) in both large regions and voxel data. Retest variability and intraclass correlation coefficient (ICC) of V-T were determined as measures of reproducibility and reliability respectively. Regional [C-11]NOP-1A uptake in the brain was high, with a peak radioactivity concentration of 4-7 SUV (standardized uptake value) and a rank order of putamen > cingulate cortex > cerebellum. Brain time-activity curves fitted well in 10 of 11 subjects by unconstrained two-tissue compartmental model. The retest variability of VT was moderately good across brain regions except cerebellum, and was similar across different modeling methods, averaging 12% for large regions and 14% for voxel-based methods. The retest reliability of VT was also moderately good in most brain regions, except thalamus and cerebellum, and was similar across different modeling methods averaging 0.46 for large regions and 0.48 for voxels having gray matter probability >20%. The lowest retest variability and highest retest reliability of VT were achieved by compartmental modeling for large regions, and by the parametric Logan method for voxel-based methods.
Moderately good reproducibility and reliability measures of VT for [C-11]NOP-1A make it a useful PET ligand for comparing NOP receptor binding between different subject groups or under different conditions in the same subject. (C) 2013 Published by Elsevier Inc.
C1 [Lohith, Talakad G.; Zoghbi, Sami S.; Morse, Cheryl L.; Araneta, Maria D. Ferraris; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Barth, Vanessa N.; Goebl, Nancy A.; Tauscher, Johannes T.] Eli Lilly & Co, Indianapolis, IN 46285 USA.
RP Lohith, TG (reprint author), NIMH, Mol Imaging Branch, 10 Ctr Dr,MSC 1026,Bldg 10,Rm B1D43K5, Bethesda, MD 20892 USA.
EM lohithhere@gmail.com; robert.innis@nih.gov
RI Tauscher, Johannes/M-5976-2016
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH); Cooperative Research and
Development Agreement with Eli Lilly Co
FX This study was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH) and by a Cooperative Research and Development Agreement
with Eli Lilly & Co. We thank Denise Rallis-Frutos, Gerald L. Hodges,
Kimberly Jenko, David Clark, Jeih-San Liow, Robert L Gladding, Paolo
Zanotti-Fregonara, and the staff of the PET Department for assistance in
completing the studies, and PMOD Technologies (Zurich, Switzerland) for
providing its image analysis and modeling software. Francois Vandenhende
(Eli Lilly & Co.) provided valuable statistical guidance. Ioline Henter
(NIMH) provided excellent editorial assistance.
NR 24
TC 8
Z9 8
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 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD FEB 15
PY 2014
VL 87
BP 89
EP 95
DI 10.1016/j.neuroimage.2013.10.068
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 301TC
UT WOS:000330554000009
PM 24225488
ER
PT J
AU Bright, MG
Bianciardi, M
de Zwart, JA
Murphy, K
Duyn, JH
AF Bright, Molly G.
Bianciardi, Marta
de Zwart, Jacco A.
Murphy, Kevin
Duyn, Jeff H.
TI Early anti-correlated BOLD signal changes of physiologic origin
SO NEUROIMAGE
LA English
DT Article
DE fMRI; Negative BOLD; Anti-correlated BOLD; Physiology; Respiratory
challenge; Deactivation
ID PRIMARY SOMATOSENSORY CORTEX; SENSORY STIMULATION; FMRI SIGNALS;
BLOOD-FLOW; BRAIN; FLUCTUATIONS; HYPERCAPNIA; ACTIVATION; DYNAMICS;
CONTRAST
AB Negative BOLD signals that are synchronous with resting state fluctuations have been observed in large vessels in the cortical sulci and surrounding the ventricles. In this study, we investigated the origin of these negative BOLD signals by applying a Cued Deep Breathing (COB) task to create transient hypocapnia and a resultant global fMRI signal decrease. We hypothesized that a global stimulus would amplify the effect in large vessels and that using a global negative (vasoconstrictive) stimulus would test whether these voxels exhibit either inherently negative or simply anti-correlated BOLD responses. Significantly anti-correlated, but positive, BOLD signal changes during respiratory challenges were identified in voxels primarily located near edges of brain spaces containing CSF. These positive BOLD responses occurred earlier than the negative COB response across most of gray matter voxels. These findings confirm earlier suggestions that in some brain regions, local, fractional changes in CSF volume may overwhelm BOLD-related signal changes, leading to signal anti-correlation. We show that regions with CDB anti-correlated signals coincide with most, but not all, of the regions with negative BOLD signal changes observed during a visual and motor stimulus task. Thus, the addition of a physiological challenge to fMRI experiments can help identify which negative BOLD signals are passive physiological anti-correlations and which may have a putative neuronal origin. Published by Elsevier Inc.
C1 [Bright, Molly G.; Bianciardi, Marta; de Zwart, Jacco A.; Duyn, Jeff H.] NINDS, Adv MRI Sect, LFMI, NIH, Bethesda, MD 20892 USA.
[Bright, Molly G.; Murphy, Kevin] Cardiff Univ, Sch Psychol, CUBRIC, Cardiff CF10 3AT, S Glam, Wales.
[Bianciardi, Marta] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Boston, MA USA.
RP Bright, MG (reprint author), Cardiff Univ, Sch Psychol, CUBRIC, Cardiff CF10 3AT, S Glam, Wales.
EM BrightMG@cardiff.ac.uk
RI Murphy, Kevin/A-1581-2010;
OI Murphy, Kevin/0000-0002-6516-313X; Bright, Molly/0000-0001-7257-9646
FU Intramural Research Program of NINDS/NIH; Wellcome Trust
FX We thank Susan Fulton Guttman for her assistance in the data
acquisition. This research was supported by the Intramural Research
Program of NINDS/NIH and the Wellcome Trust.
NR 35
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Z9 4
U1 1
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD FEB 15
PY 2014
VL 87
BP 287
EP 296
DI 10.1016/j.neuroimage.2013.10.055
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 301TC
UT WOS:000330554000028
PM 24211818
ER
PT J
AU Danthi, N
Wu, CO
Shi, PB
Lauer, M
AF Danthi, Narasimhan
Wu, Colin O.
Shi, Peibei
Lauer, Michael
TI Percentile Ranking and Citation Impact of a Large Cohort of National
Heart, Lung, and Blood Institute-Funded Cardiovascular R01 Grants
SO CIRCULATION RESEARCH
LA English
DT Article
DE bibliometrics; National Heart; Lung; and Blood Institute (U; S; )
ID SCIENTIFIC PRODUCTIVITY
AB Rationale: Funding decisions for cardiovascular R01 grant applications at the National Heart, Lung, and Blood Institute (NHLBI) largely hinge on percentile rankings. It is not known whether this approach enables the highest impact science.
Objective: Our aim was to conduct an observational analysis of percentile rankings and bibliometric outcomes for a contemporary set of funded NHLBI cardiovascular R01 grants.
Methods and Results: We identified 1492 investigator-initiated de novo R01 grant applications that were funded between 2001 and 2008 and followed their progress for linked publications and citations to those publications. Our coprimary end points were citations received per million dollars of funding, citations obtained <2 years of publication, and 2-year citations for each grant's maximally cited paper. In 7654 grant-years of funding that generated $3004 million of total National Institutes of Health awards, the portfolio yielded 16 793 publications that appeared between 2001 and 2012 (median per grant, 8; 25th and 75th percentiles, 4 and 14; range, 0-123), which received 2 224 255 citations (median per grant, 1048; 25th and 75th percentiles, 492 and 1932; range, 0-16 295). We found no association between percentile rankings and citation metrics; the absence of association persisted even after accounting for calendar time, grant duration, number of grants acknowledged per paper, number of authors per paper, early investigator status, human versus nonhuman focus, and institutional funding. An exploratory machine learning analysis suggested that grants with the best percentile rankings did yield more maximally cited papers.
Conclusions: In a large cohort of NHLBI-funded cardiovascular R01 grants, we were unable to find a monotonic association between better percentile ranking and higher scientific impact as assessed by citation metrics.
C1 [Danthi, Narasimhan] NHLBI, Adv Technol & Surg Branch, Bethesda, MD 20824 USA.
[Wu, Colin O.; Shi, Peibei] NHLBI, Off Biostat Res, Bethesda, MD 20824 USA.
[Lauer, Michael] NHLBI, Off Director, Div Cardiovasc Sci, Bethesda, MD 20824 USA.
RP Lauer, M (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8128, Bethesda, MD 20824 USA.
EM lauerm@nhlbi.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 18
TC 27
Z9 28
U1 1
U2 16
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD FEB 14
PY 2014
VL 114
IS 4
BP 600
EP 606
DI 10.1161/CIRCRESAHA.114.302656
PG 7
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA AG7GT
UT WOS:000335587000010
PM 24406983
ER
PT J
AU Anderluh, A
Klotzsch, E
Reismann, AWAF
Brameshuber, M
Kudlacek, O
Newman, AH
Sitte, HH
Schutz, GJ
AF Anderluh, Andreas
Klotzsch, Enrico
Reismann, Alexander W. A. F.
Brameshuber, Mario
Kudlacek, Oliver
Newman, Amy Hauck
Sitte, Harald H.
Schuetz, Gerhard J.
TI Single Molecule Analysis Reveals Coexistence of Stable Serotonin
Transporter Monomers and Oligomers in the Live Cell Plasma Membrane
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Membrane Proteins; Protein Dynamics; Protein-Protein Interactions;
Serotonin Transporters; Single Molecule Biophysics; Oligomerization
ID HUMAN DOPAMINE TRANSPORTER; ENERGY-TRANSFER MICROSCOPY; RAT GABA
TRANSPORTER-1; NEUROTRANSMITTER TRANSPORTERS; LIVING CELLS;
TRANSMEMBRANE SEGMENT; COCAINE ANALOGS; CROSS-LINKING; PROTEIN;
TRAFFICKING
AB Background: The serotonin transporter (SERT) terminates synaptic signaling by reuptake of the neurotransmitter serotonin. Results: Interaction kinetics and number of subunits are elucidated by single molecule brightness analysis of SERT complexes. Conclusion: The oligomeric state of SERT complexes is stably determined before being integrated into the plasma membrane. Significance: The results reveal the first evidence for kinetic trapping of preformed neurotransmitter transporter oligomers.
The human serotonin transporter (hSERT) is responsible for the termination of synaptic serotonergic signaling. Although there is solid evidence that SERT forms oligomeric complexes, the exact stoichiometry of the complexes and the fractions of different coexisting oligomeric states still remain enigmatic. Here we used single molecule fluorescence microscopy to obtain the oligomerization state of the SERT via brightness analysis of single diffraction-limited fluorescent spots. Heterologously expressed SERT was labeled either with the fluorescent inhibitor JHC 1-64 or via fusion to monomeric GFP. We found a variety of oligomerization states of membrane-associated transporters, revealing molecular associations larger than dimers and demonstrating the coexistence of different degrees of oligomerization in a single cell; the data are in agreement with a linear aggregation model. Furthermore, oligomerization was found to be independent of SERT surface density, and oligomers remained stable over several minutes in the live cell plasma membrane. Together, the results indicate kinetic trapping of preformed SERT oligomers at the plasma membrane.
C1 [Anderluh, Andreas; Klotzsch, Enrico; Reismann, Alexander W. A. F.; Brameshuber, Mario; Schuetz, Gerhard J.] Vienna Univ Technol, Inst Appl Phys, A-1060 Vienna, Austria.
[Kudlacek, Oliver; Sitte, Harald H.] Med Univ Vienna, Inst Pharmacol, Ctr Physiol & Pharmacol, A-1090 Vienna, Austria.
[Newman, Amy Hauck] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program, Baltimore, MD 21224 USA.
RP Klotzsch, E (reprint author), Vienna Univ Technol, Inst Appl Phys, Getreidemarkt 9, A-1060 Vienna, Austria.
EM enricoklotzsch@gmail.com; schuetz@iap.tuwien.ac.at
RI Klotzsch, Enrico/J-8831-2012; Schutz, Gerhard/B-1243-2008;
OI Klotzsch, Enrico/0000-0002-7577-9042; Schutz,
Gerhard/0000-0003-1542-1089; Brameshuber, Mario/0000-0001-8672-2255;
Sitte, Harald/0000-0002-1339-7444
FU Austrian Science Fund/FWF Projects [F3506-B20, F3519-B20]; National
Institute on Drug Abuse-Intramural Research Program; Federation of
European Biochemical Societies
FX This work was supported by the Austrian Science Fund/FWF Projects
F3506-B20 (to H. H. S.) and F3519-B20 (to G. J. S.) and by the National
Institute on Drug Abuse-Intramural Research Program (to A. H. N.).;
Supported by a long term fellowship from the Federation of European
Biochemical Societies. To whom correspondence may be addressed. Tel.:
43-01-58801134884; E-mail: enricoklotzsch@gmail.com.
NR 50
TC 20
Z9 20
U1 1
U2 17
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 14
PY 2014
VL 289
IS 7
BP 4387
EP 4394
DI 10.1074/jbc.M113.531632
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AA9HG
UT WOS:000331403800049
PM 24394416
ER
PT J
AU Huang, CH
Chu, YR
Ye, YH
Chen, X
AF Huang, Chih-Hsiang
Chu, Yue-Ru
Ye, Yihong
Chen, Xin
TI Role of HERP and a HERP-related Protein in HRD1-dependent Protein
Degradation at the Endoplasmic Reticulum
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Cell Biology; ER Quality Control; Protein Degradation; Protein
Translocation; Ubiquitin Ligase
ID ER-ASSOCIATED DEGRADATION; UBIQUITIN-LIGASE; QUALITY-CONTROL; PATHWAY;
COMPLEX; STRESS; HOMEOSTASIS; HRD1P
AB Misfolded proteins of the endoplasmic reticulum (ER) are retrotranslocated to the cytosol and degraded by the proteasome via a process termed ER-associated degradation (ERAD). The precise mechanism of retrotranslocation is unclear. Here, we use several lumenal ERAD substrates targeted for degradation by the ubiquitin ligase HRD1 including SHH (sonic hedgehog) and NHK (null Hong Kong 1-antitrypsin) to study the geometry, organization, and regulation of the HRD1-containing ERAD machinery. We report a new HRD1-associated membrane protein named HERP2, which is homologous to the previously identified HRD1 partner HERP1. Despite sequence homology, HERP2 is constitutively expressed in cells, whereas HERP1 is highly induced by ER stress. We find that these proteins are required for efficient degradation of both glycosylated and nonglycosylated SHH proteins as well as NHK. In cells depleted of HERPs, SHH proteins are largely trapped inside the ER with a fraction of the stabilized SHH protein bound to the HRD1-SEL1L ligase complex. Ubiquitination of SHH is significantly attenuated in the absence of HERPs, suggesting a defect in retrotranslocation. Both HERP proteins interact with HRD1 through a region located in the cytosol. However, unlike its homolog in Saccharomyces cerevisiae, HERPs do not regulate HRD1 stability or oligomerization status. Instead, they help recruit DERL2 to the HRD1-SEL1L complex. Additionally, the UBL domain of HERP1 also seems to have a function independent of DERL2 recruitment in ERAD. Our studies have revealed a critical scaffolding function for mammalian HERP proteins that is required for forming an active retrotranslocation complex containing HRD1, SEL1L, and DERL2.
C1 [Huang, Chih-Hsiang; Chu, Yue-Ru; Chen, Xin] Natl Hlth Res Inst, Inst Biotechnol & Pharmaceut Res, Miaoli 35053, Taiwan.
[Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Xin] China Med Univ, Grad Inst Basic Med Sci, Taichung 40402, Taiwan.
RP Ye, YH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM yihongy@niddk.nih.gov; xchen@nhri.org.tw
FU National Research Programs for Genomic Medicine (NRPGM), National
Science Council; National Health Research Institutes, Taiwan, China
FX This work was supported by the National Research Programs for Genomic
Medicine (NRPGM), National Science Council, and National Health Research
Institutes, Taiwan, China. This work was supported by the National
Research Programs for Genomic Medicine (NRPGM), National Science Council
and National Health Research Institutes, Taiwan, China.
NR 28
TC 7
Z9 7
U1 1
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 14
PY 2014
VL 289
IS 7
BP 4444
EP 4454
DI 10.1074/jbc.M113.519561
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AA9HG
UT WOS:000331403800054
PM 24366871
ER
PT J
AU Sokolowska, M
Chen, LY
Eberlein, M
Martinez-Anton, A
Liu, YQ
Alsaaty, S
Qi, HY
Logun, C
Horton, M
Shelhamer, JH
AF Sokolowska, Milena
Chen, Li-Yuan
Eberlein, Michael
Martinez-Anton, Asuncion
Liu, Yueqin
Alsaaty, Sara
Qi, Hai-Yan
Logun, Carolea
Horton, Maureen
Shelhamer, James H.
TI Low Molecular Weight Hyaluronan Activates Cytosolic Phospholipase
A(2)alpha and Eicosanoid Production in Monocytes and Macrophages
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Cyclooxygenase (COX) Pathway; Eicosanoid; Extracellular Matrix;
Inflammation; Monocytes; Toll-like Receptors (TLR); Hyaluronan;
Prostaglandin; cPLA2; Macrophage Polarization
ID APC(DELTA-716) KNOCKOUT MICE; HUMAN LUNG-CELLS; NF-KAPPA-B; INTESTINAL
POLYPOSIS; SERUM HYALURONAN; NEGATIVE REGULATOR; MOUSE MACROPHAGES;
INTERFERON-GAMMA; BINDING PROTEINS; GENE-EXPRESSION
AB Hyaluronan (HA) is the major glycosaminoglycan in the extracellular matrix. During inflammation, there is an increased breakdown of HA, resulting in the accumulation of low molecular weight (LMW) HA and activation of monocytes and macrophages. Eicosanoids, derived from the cytosolic phospholipase A(2) group IVA (cPLA(2)) activation, are potent lipid mediators also attributed to acute and chronic inflammation. The aim of this study was to determine the effect of LMW HA on cPLA(2) activation, arachidonic acid (AA) release, and subsequent eicosanoid production and to examine the receptors and downstream mechanisms involved in these processes in monocytes and differently polarized macrophages. LMW HA was a potent stimulant of AA release in a time- and dose-dependent manner, induced cPLA(2), ERK1/2, p38, and JNK phosphorylation, as well as activated COX2 expression and prostaglandin (PG) E-2 production in primary human monocytes, murine RAW 264.7, and wild-type bone marrow-derived macrophages. Specific cPLA(2) inhibitor blocked HA-induced AA release and PGE(2) production in all of these cells. Using CD44, TLR4, TLR2, MYD88, RHAMM or STAB2 siRNA-transfected macrophages and monocytes, we found that AA release, cPLA(2), ERK1/2, p38, and JNK phosphorylation, COX2 expression, and PGE(2) production were activated by LMW HA through a TLR4/MYD88 pathway. Likewise, PGE(2) production and COX2 expression were blocked in Tlr4(-/-) and Myd88(-/-) mice, but not in Cd44(-/-) mice, after LMW HA stimulation. Moreover, we demonstrated that LMW HA activated the M1 macrophage phenotype with the unique cPLA(2)/COX2(high) and COX1/ALOX15/ALOX5/LTA4H(low) gene and PGE(2)/PGD(2)/15-HETEhigh and LXA(4)(low) eicosanoid profile. These findings reveal a novel link between HA-mediated inflammation and lipid metabolism.
C1 [Sokolowska, Milena; Chen, Li-Yuan; Eberlein, Michael; Martinez-Anton, Asuncion; Liu, Yueqin; Alsaaty, Sara; Qi, Hai-Yan; Logun, Carolea; Shelhamer, James H.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Horton, Maureen] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA.
RP Shelhamer, JH (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jshelhamer@cc.nih.gov
RI Martinez Anton, Asuncion/A-5806-2017
OI Martinez Anton, Asuncion/0000-0001-9758-5911
FU National Institutes of Health
FX This work was supported, in whole or in part, by National Institutes of
Health intramural program.
NR 107
TC 20
Z9 20
U1 2
U2 13
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 14
PY 2014
VL 289
IS 7
BP 4470
EP 4488
DI 10.1074/jbc.M113.515106
PG 19
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AA9HG
UT WOS:000331403800056
PM 24366870
ER
PT J
AU Malek, NP
Schmidt, S
Huber, P
Manns, MP
Greten, TF
AF Malek, Nisar P.
Schmidt, Sebastian
Huber, Petra
Manns, Michael P.
Greten, Tim F.
TI The Diagnosis and Treatment of Hepatocellular Carcinoma
SO DEUTSCHES ARZTEBLATT INTERNATIONAL
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; CHRONIC LIVER-DISEASE; FINE-NEEDLE BIOPSY;
ACID-ENHANCED MRI; RADIOFREQUENCY ABLATION; RISK-FACTORS;
DIABETIC-PATIENTS; CHEMOEMBOLIZATION; CIRRHOSIS; HEPATITIS
AB Background: The incidence of hepatocellular carcinoma (HCC) has continued to rise in recent years. This increase has been attributed to alcohol-induced liver diseases, metabolic syndrome, and the rising number of hepatitis B and C viral infections.
Methods: Pertinent publications (2000-2011) were retrieved by a systematic Medline search. In seven different subject areas, 41 key questions were defined; 15 of them were answered on the basis of a primary search. In addition, original-source guidelines that are currently available from around the world were assessed and utilized with the aid of a systematic instrument for the evaluation of guidelines (DELBI).
Results: All patients with chronic liver disease should undergo ultrasonography every six months for the early detection of HCC. Measurement of the alpha-fetoprotein (AFP) concentration is not obligatory, as this test is relatively insensitive when used for early detection. If ultrasonography reveals a mass, a tomographic imaging study with contrast should be obtained; the latter may reveal a characteristic pattern of contrast enhancement that can be accepted as definitive evidence of HCC. Fine-needle biopsy has a sensitivity and specificity of over 90% for the diagnosis of HCC. Any patient in whom HCC has been diagnosed should be referred to a center where potentially curative treatments (surgery, transplantation, local ablation) can be considered. Radiofrequency ablation (RFA) is now performed instead of percutaneous ethanol instillation. For patients with advanced tumors, sorafenib should only be offered to those in Child-Pugh stage A. This drug has been found to prolong mean overall survival from 7.9 to 10.7 months.
Conclusion: HCC poses particular diagnostic and therapeutic challenges that are best met with an interdisciplinary management approach.
C1 [Malek, Nisar P.] Univ Tubingen, Dept Med, Tubingen, Germany.
[Schmidt, Sebastian; Huber, Petra; Manns, Michael P.] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany.
[Greten, Tim F.] NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Malek, NP (reprint author), Univ Klinikum Tubingen, Med Klin 1, Otfried Muller Str 10, Tubingen, Germany.
EM nisar.malek@med.uni-tuebingen.de
RI Greten, Tim/B-3127-2015
OI Greten, Tim/0000-0002-0806-2535
FU German Cancer Aid through its Oncology Guideline Program
FX The preparation of the guideline was funded by German Cancer Aid through
its Oncology Guideline Program.
NR 43
TC 25
Z9 29
U1 1
U2 11
PU DEUTSCHER AERZTE-VERLAG GMBH
PI COLOGNE
PA DIESELSTRABE 2, POSTFACH 400265, D-50859 COLOGNE, GERMANY
SN 1866-0452
J9 DTSCH ARZTEBL INT
JI Dtsch. Arztebl. Int.
PD FEB 14
PY 2014
VL 111
IS 7
BP 101
EP U13
DI 10.3238/arztebl.2014.0101
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC9KE
UT WOS:000332852500001
PM 24622679
ER
PT J
AU Lamb, JS
Chadwick, RS
AF Lamb, Jessica S.
Chadwick, Richard S.
TI Phase of Shear Vibrations within Cochlear Partition Leads to Activation
of the Cochlear Amplifier
SO PLOS ONE
LA English
DT Article
ID HAIR CELL MOTILITY; TECTORIAL MEMBRANE; BASILAR-MEMBRANE;
TRAVELING-WAVES; MODEL; MECHANICS; EAR; SUBPARTITIONS; AMPLIFICATION;
TRANSDUCTION
AB Since Georg von Bekesy laid out the place theory of the hearing, researchers have been working to understand the remarkable properties of mammalian hearing. Because access to the cochlea is restricted in live animals, and important aspects of hearing are destroyed in dead ones, models play a key role in interpreting local measurements. Wentzel-Kramers-Brillouin (WKB) models are attractive because they are analytically tractable, appropriate to the oblong geometry of the cochlea, and can predict wave behavior over a large span of the cochlea. Interest in the role the tectorial membrane (TM) plays in cochlear tuning led us to develop models that directly interface the TM with the cochlear fluid. In this work we add an angled shear between the TM and reticular lamina (RL), which serves as an input to a nonlinear active force. This feature plus a novel combination of previous work gives us a model with TM-fluid interaction, TM-RL shear, a nonlinear active force and a second wave mode. The behavior we get leads to the conclusion the phase between the shear and basilar membrane (BM) vibration is critical for amplification. We show there is a transition in this phase that occurs at a frequency below the cutoff, which is strongly influenced by TM stiffness. We describe this mechanism of sharpened BM velocity profile, which demonstrates the importance of the TM in overall cochlear tuning and offers an explanation for the response characteristics of the Tectb mutant mouse.
C1 [Lamb, Jessica S.; Chadwick, Richard S.] NIDCD, Sect Auditory Mech, Bethesda, MD 20892 USA.
RP Chadwick, RS (reprint author), NIDCD, Sect Auditory Mech, Bethesda, MD 20892 USA.
EM chadwick@helix.nih.gov
FU National Institute on Deafness and other Communication Disorders
[DC00033]
FX This work was supported by the intramural program project DC00033 in the
National Institute on Deafness and other Communication Disorders. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 34
TC 6
Z9 6
U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 14
PY 2014
VL 9
IS 2
AR e85969
DI 10.1371/journal.pone.0085969
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA7IR
UT WOS:000331271500006
PM 24551037
ER
PT J
AU Wang, ZW
Dela Cruz, R
Ji, F
Guo, S
Zhang, JH
Wang, Y
Feng, GS
Birnbaumer, L
Jiang, MS
Chu, WM
AF Wang, Zhanwei
Dela Cruz, Rica
Ji, Fang
Guo, Sheng
Zhang, Jianhua
Wang, Ying
Feng, Gen-Sheng
Birnbaumer, Lutz
Jiang, Meisheng
Chu, Wen-Ming
TI G(i)alpha proteins exhibit functional differences in the activation of
ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer
cells
SO CELL COMMUNICATION AND SIGNALING
LA English
DT Article
DE G(i)alpha proteins; receptor tyrosine kinase (RTK); EGFR; Gab1; Shp2;
EGF; Akt; mTORC1; ERK1/2; breast cancer
ID COUPLED RECEPTORS; KINASE ACTIVATION; SIGNALING PATHWAY; DRUG DISCOVERY;
EGF RECEPTOR; IN-VIVO; GAB1; INSULIN; METASTASIS; LIVER
AB Background: In a classic model, G(i)alpha proteins including G(i1)alpha, G(i2)alpha and G(i3)alpha are important for transducing signals from Gia protein-coupled receptors (G(i)alpha PCRs) to their downstream cascades in response to hormones and neurotransmitters. Our previous study has suggested that G(i1)alpha, G(i2)alpha and G(i3)alpha are also important for the activation of the PI3K/Akt/mTORC1 pathway by epidermal growth factor (EGF) and its family members. However, a genetic role of these Gia proteins in the activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) by EGF is largely unknown. Further, it is not clear whether these Gia proteins are also engaged in the activation of both the Akt/mTORC1 and ERK1/2 pathways by other growth factor family members. Additionally, a role of these Gia proteins in breast cancer remains to be elucidated.
Results: We found that Gi1/3 deficient MEFs with the low expression level of G(i2)alpha showed defective ERK1/2 activation by EGFs, IGF-1 and insulin, and Akt and mTORC1 activation by EGFs and FGFs. Gi1/2/3 knockdown breast cancer cells exhibited a similar defect in the activations and a defect in in vitro growth and invasion. The G(i)alpha proteins associated with RTKs, Gab1, FRS2 and Shp2 in breast cancer cells and their ablation impaired Gab1's interactions with Shp2 in response to EGF and IGF-1, or with FRS2 and Grb2 in response to bFGF.
Conclusions: G(i)alpha proteins differentially regulate the activation of Akt, mTORC1 and ERK1/2 by different families of growth factors. G(i)alpha proteins are important for breast cancer cell growth and invasion.
C1 [Wang, Zhanwei; Dela Cruz, Rica; Guo, Sheng; Zhang, Jianhua; Chu, Wen-Ming] Univ Hawaii, Ctr Canc, Canc Biol Program, Honolulu, HI 96813 USA.
[Ji, Fang] Shanghai Jiao Tong Univ, Sch Med, Dept Obstet & Gynecol, Ren Ji Hosp, Shanghai 200030, Peoples R China.
[Guo, Sheng; Zhang, Jianhua] Shanghai Jiao Tong Univ, Dept Pediat, Shanghai Peoples Hosp 6, Shanghai 200030, Peoples R China.
[Wang, Ying; Jiang, Meisheng] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
[Feng, Gen-Sheng] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92037 USA.
[Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
RP Jiang, MS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
EM jm@ucla.edu; wchu@cc.hawaii.edu
RI wang, zhanwei/F-9958-2016
FU DOD [PR054819]; NIH [AI054128, DK069771]; Hawaii Community Foundation;
Leukemia and Lymphoma Society; National Institute of Environmental
Health Sciences, NIH [201-101643]
FX We are grateful to Drs. Cong Cao, Xuesong Huang and John Marshall for
their valuable advice and technical support. We thank Dr. David Ward for
critical discussion. This work was supported in part by grants from DOD
(PR054819), NIH (AI054128), Hawaii Community Foundation and Leukemia and
Lymphoma Society to WMC, NIH (DK069771) to MJ, and in part from the
Intramural Research Program of the National Institute of Environmental
Health Sciences, NIH (project 201-101643) to LB.
NR 46
TC 4
Z9 4
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1478-811X
J9 CELL COMMUN SIGNAL
JI Cell Commun. Signal.
PD FEB 13
PY 2014
VL 12
AR 10
DI 10.1186/1478-811X-12-10
PG 12
WC Cell Biology
SC Cell Biology
GA AD5FM
UT WOS:000333277500001
PM 24521094
ER
PT J
AU Tang, J
Li, Y
Lyon, K
Camps, J
Dalton, S
Ried, T
Zhao, S
AF Tang, J.
Li, Y.
Lyon, K.
Camps, J.
Dalton, S.
Ried, T.
Zhao, S.
TI Cancer driver-passenger distinction via sporadic human and dog cancer
comparison: a proof-of-principle study with colorectal cancer
SO ONCOGENE
LA English
DT Article
DE CRC driver-passenger distinction; sporadic canine CRCs; human-dog
comparison; epithelial cell apicobasal polarity; genomic
amplifications/deletions
ID CELL POLARITY; TUMOR-SUPPRESSOR; DOMESTIC DOG; GENOME; SEQUENCE;
PROTEIN; COLON; TRANSITION; NETWORK; BREAST
AB Herein we report a proof-of-principle study illustrating a novel dog-human comparison strategy that addresses a central aim of cancer research, namely cancer driver-passenger distinction. We previously demonstrated that sporadic canine colorectal cancers (CRCs) share similar molecular pathogenesis mechanisms as their human counterparts. In this study, we compared the genome-wide copy number abnormalities between 29 human and 10 canine sporadic CRCs. This led to the identification of 73 driver candidate genes (DCGs), altered in both species, and with 27 from the whole genome and 46 from dog-human genomic rearrangement breakpoint (GRB) regions, as well as 38 passenger candidate genes (PCGs), altered in humans only and located in GRB regions. We noted that DCGs significantly differ from PCGs in every analysis conducted to assess their cancer relevance and biological functions. Importantly, although PCGs are not enriched in any specific functions, DCGs possess significantly enhanced functionality closely associated with cell proliferation and death regulation, as well as with epithelial cell apicobasal polarity establishment/maintenance. These observations support the notion that, in sporadic CRCs of both species, cell polarity genes not only contribute in preventing cancer cell invasion and spreading, but also likely serve as tumor suppressors by modulating cell growth. This pilot study validates our novel strategy and has uncovered four new potential cell polarity and colorectal tumor suppressor genes (RASA3, NUPL1, DENND5A and AVL9). Expansion of this study would make more driver-passenger distinctions for cancers with large genomic amplifications or deletions, and address key questions regarding the relationship between cancer pathogenesis and epithelial cell polarity control in mammals.
C1 [Tang, J.; Li, Y.; Lyon, K.; Dalton, S.; Zhao, S.] Univ Georgia, Inst Bioinformat, Dept Biochem & Mol Biol, Athens, GA 30602 USA.
[Camps, J.; Ried, T.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Zhao, S (reprint author), Univ Georgia, Inst Bioinformat, Dept Biochem & Mol Biol, B304B Life Sci Bldg,120 Green St, Athens, GA 30602 USA.
EM szhao@bmb.uga.edu
RI Tang, Jie/D-3764-2015
OI Tang, Jie/0000-0002-3991-2539
FU American Cancer Society; Georgia Cancer Coalition; NCI [P50 CA128613]
FX We thank Ms Huan Xiong for her work; Dr Bert Vogelstein for providing
various CRC lines and Dr Timothy A Chan of Memorial Sloan-Kettering
Cancer Center for providing the IHA cells; and Drs Dong M Shin, J David
Puett, Claiborne Glover, Georgia Chen, and Lisa J Stubb for their help
and advice on this study. This work was funded by the American Cancer
Society and the Georgia Cancer Coalition (principal investigator (PI): S
Zhao), as well as NCI P50 CA128613 (PI: Dr Dong M Shin) and GM085354
(PI: Dr Stephen Dalton).
NR 50
TC 3
Z9 4
U1 1
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD FEB 13
PY 2014
VL 33
IS 7
BP 814
EP 822
DI 10.1038/onc.2013.17
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA AB2MN
UT WOS:000331626900002
PM 23416983
ER
PT J
AU Shukla, A
Edwards, R
Yang, Y
Hahn, A
Folkers, K
Ding, J
Padmakumar, VC
Cataisson, C
Suh, KS
Yuspa, SH
AF Shukla, A.
Edwards, R.
Yang, Y.
Hahn, A.
Folkers, K.
Ding, J.
Padmakumar, V. C.
Cataisson, C.
Suh, K. S.
Yuspa, S. H.
TI CLIC4 regulates TGF-beta-dependent myofibroblast differentiation to
produce a cancer stroma
SO ONCOGENE
LA English
DT Article
DE CLIC; alpha-SMA; p38; microenvironment; PPM1a
ID EPITHELIAL-MESENCHYMAL TRANSITION; CHLORIDE CHANNEL PROTEIN; MUSCLE
ACTIN EXPRESSION; CONTRACTILE ACTIVITY; MOLECULAR-CLONING;
CRYSTAL-STRUCTURE; CELL CARCINOMA; FIBROBLASTS; GROWTH; PHOSPHATASE
AB Cancer stroma has a profound influence on tumor development and progression. The conversion of fibroblasts to activated myofibroblasts is a hallmark of reactive tumor stroma. Among a number of factors involved in this conversion, transforming growth factor (TGF)-beta has emerged as a major regulator. CLIC4, an integral protein in TGF-beta signaling, is highly upregulated in stroma of multiple human cancers, and overexpression of CLIC4 in stromal cells enhances the growth of cancer xenografts. In this study, we show that conditioned media from tumor cell lines induces expression of both CLIC4 and the myofibroblast marker alpha smooth muscle actin (alpha-SMA) in stromal fibroblasts via TGF-beta signaling. Genetic ablation of CLIC4 in primary fibroblasts prevents or reduces constitutive or TGF-beta-induced expression of alpha-SMA and extracellular matrix components that are markers of myofibroblasts. CLIC4 is required for the activation of p38 map kinase by TGF-beta, a pathway that signals myofibroblast conversion in stromal cells. This requirement involves the interaction of CLIC4 with PPM1a, the selective phosphatase of activated p38. Conditioned media from fibroblasts overexpressing CLIC4 increases tumor cell migration and invasion in a TGF-beta-dependent manner and promotes epithelial to mesenchymal transition indicating that high stromal CLIC4 serves to enhance tumor invasiveness and progression. Thus, CLIC4 is significantly involved in the development of a nurturing tumor microenvironment by enhancing TGF-beta signaling in a positive feedback loop. Targeting CLIC4 in tumor stroma should be considered as a strategy to mitigate some of the tumor enhancing effects of the cancer stroma.
C1 [Shukla, A.; Edwards, R.; Yang, Y.; Hahn, A.; Folkers, K.; Padmakumar, V. C.; Cataisson, C.; Yuspa, S. H.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
[Ding, J.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Suh, K. S.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA.
RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, 37 Convent Dr, Bethesda, MD 20892 USA.
EM yuspas@mail.nih.gov
RI Shukla, Anjali/G-4046-2014
FU Center for Cancer Research, National Cancer Institute
FX We thank Dr Lalage Wakefield, National Cancer Institute, Bethesda for
providing Smad3 KO mice and MI, MII, MIII, MIV cell lines, Dr Ed Leof,
Department of Biochemistry and Molecular Biology, Mayo Clinic, Minnesota
for providing anti-phospho Smad3 antibody and Dr Akira Oshima, National
Cancer Institute for help with immunofluorescence. This work was
supported by the intramural research program of the Center for Cancer
Research, National Cancer Institute.
NR 54
TC 15
Z9 17
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD FEB 13
PY 2014
VL 33
IS 7
BP 842
EP 850
DI 10.1038/onc.2013.18
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA AB2MN
UT WOS:000331626900005
PM 23416981
ER
PT J
AU Okunola-Bakare, OM
Cao, JJ
Kopajtic, T
Katz, JL
Loland, CJ
Shi, L
Newman, AH
AF Okunola-Bakare, Oluyomi M.
Cao, Jianjing
Kopajtic, Theresa
Katz, Jonathan L.
Loland, Claus J.
Shi, Lei
Newman, Amy Hauck
TI Elucidation of Structural Elements for Selectivity across Monoamine
Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil)
Analogues
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID DOPAMINE TRANSPORTER; SEROTONIN TRANSPORTER; ALIPHATIC DISULFIDES;
CHEMISTRY; MUTAGENESIS; MEDICATION; INHIBITOR; COGNITION; BINDING;
POTENT
AB 2-[(Diphenylmethyl)sulfinyl]acetamide (modafinil, (+/-)-1) is a unique dopamine uptake inhibitor that binds the dopamine transporter (DAT) differently than cocaine and may have potential for the treatment of psychostimulant abuse. To further investigate structural requirements for this divergent binding mode, novel thio- and sulfinylacetamide and ethanamine analogues of (+/-)-1 were synthesized wherein (1) the diphenyl rings were substituted with methyl, trifluoromethyl, and halogen substituents and (2) substituents were added to the terminal amide/amine nitrogen. Halogen substitution of the diphenyl rings of (+/-)-1 gave several amide analogues with improved binding affinity for DAT and robust selectivity over the serotonin transporter (SERT), whereas affinity improved at SERT over DAT for the p-halo-substituted amine analogues. Molecular docking studies, using a subset of analogues with DAT and SEAT homology models, and functional data obtained with DAT (A480T) and SERT (T497A) mutants defined a role for TM10 in the substrate/inhibitor S1 binding sites of DAT and SERT.
C1 [Okunola-Bakare, Oluyomi M.; Cao, Jianjing; Newman, Amy Hauck] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Kopajtic, Theresa; Katz, Jonathan L.] NIDA, Psychobiol Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Loland, Claus J.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Neurosci & Pharmacol, DK-1165 Copenhagen, Denmark.
[Shi, Lei] Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA.
[Shi, Lei] Cornell Univ, Weill Med Coll, Inst Computat Biomed, New York, NY 10065 USA.
RP Newman, AH (reprint author), NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov
RI Loland, Claus/E-5975-2014;
OI Loland, Claus/0000-0002-1773-1446; Katz, Jonathan/0000-0002-1068-1159
FU National Institute on Drug Abuse Intramural Research Program; Lundbeck
Foundation; Danish Council for Independent Research Sapere Aude program
FX Support for this research was provided to A.H.N., O.M.O.-B., J.C., T.K.,
and J.L.K. by the National Institute on Drug Abuse Intramural Research
Program. C.J.L. is supported by the Lundbeck Foundation and the Danish
Council for Independent Research Sapere Aude program.
NR 31
TC 6
Z9 6
U1 3
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD FEB 13
PY 2014
VL 57
IS 3
BP 1000
EP 1013
DI 10.1021/jm401754x
PG 14
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AB0OW
UT WOS:000331493000032
PM 24494745
ER
PT J
AU Foley, TL
Rai, G
Yasgar, A
Daniel, T
Baker, HL
Attene-Ramos, M
Kosa, NM
Leister, W
Burkart, MD
Jadhav, A
Simeonov, A
Maloney, DJ
AF Foley, Timothy L.
Rai, Ganesha
Yasgar, Adam
Daniel, Thomas
Baker, Heather L.
Attene-Ramos, Matias
Kosa, Nicolas M.
Leister, William
Burkart, Michael D.
Jadhav, Ajit
Simeonov, Anton
Maloney, David J.
TI 4-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)-N-(4-methoxypyridin-2-yl)pi
perazine-1-carbothioamide (ML267), a Potent Inhibitor of Bacterial
Phosphopantetheinyl Transferase That Attenuates Secondary Metabolism and
Thwarts Bacterial Growth
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID CARRIER PROTEIN SYNTHASE; FATTY-ACID SYNTHESIS; SMALL-MOLECULE
INHIBITION; CROSS-COUPLING REACTIONS; STAPHYLOCOCCUS-AUREUS;
ESCHERICHIA-COLI; C-N; PSEUDOMONAS-AERUGINOSA; ANTIBACTERIAL DISCOVERY;
BACILLUS-SUBTILIS
AB 4'-Phosphopantetheinyl transferases (PPTases) catalyze a post-translational modification essential to bacterial cell viability and virulence. We present the discovery and medicinal chemistry optimization of 2-pyridinyl-N-(4-aryl)-piperazine-1-carbothioamides, which exhibit submicromolar inhibition of bacterial Sfp-PPTase with no activity toward the human orthologue. Moreover, compounds within this class possess antibacterial activity in the absence of a rapid cytotoxic response in human cells. An advanced analogue of this series, ML267 (55), was found to attenuate production of an Sfp-PPTase-dependent metabolite when applied to Bacillus subtilis at sublethal doses. Additional testing revealed antibacterial activity against methicillin-resistant Staphylococcus aureus, and chemical genetic studies implicated efflux as a mechanism for resistance in Escherichia coli. Additionally, we highlight the in vitro absorption, distribution, metabolism; and excretion and in vivo pharmacokinetic profiles of compound 55 to further demonstrate the potential utility of this small-molecule inhibitor.
C1 [Foley, Timothy L.; Rai, Ganesha; Yasgar, Adam; Daniel, Thomas; Baker, Heather L.; Attene-Ramos, Matias; Leister, William; Jadhav, Ajit; Simeonov, Anton; Maloney, David J.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Kosa, Nicolas M.; Burkart, Michael D.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
RP Simeonov, A (reprint author), NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
EM asimeono@mail.nih.gov; maloneyd@mail.nih.gov
FU National Center for Advancing Translational Sciences; Molecular
Libraries Initiative of the National Institutes of Health Roadmap for
Medical Research [U54MH084681]; NIH [R21AI090213, R01GM094924]
FX T.L.F., G.R., A.Y., T.D., H.L.B., M.A.-R., W.L., A.J., A.S., and D.J.M.
were supported by the intramural research program of the National Center
for Advancing Translational Sciences and the Molecular Libraries
Initiative of the National Institutes of Health Roadmap for Medical
Research (Grant U54MH084681). N.M.K. and M.D.B. were supported by NIH
Grants R21AI090213 and R01GM094924. We thank Sam Michael, Michael Balcom
(deceased), and Richard Jones for automation support, Paul Shinn and
Danielle van Leer for the assistance with compound management, Edward H.
Kerns and Kimloan Nguyen for determination of in vitro ADME properties,
Elizabeth Fernandez, Christopher Leclair, and Heather Baker for
assistance with compound purification and processing, Mohamed Marahiel
(Philipps-Universitat Marburg), the Bacillus Genomic Stock Center, and
The National BioResource Project of the Japanese National Institute for
Genetics for bacterial strains, Udo Oppermann (University of Oxford) for
the human PPTase expression plasmid, and Victor Torres (Anti-infectives
Screening Core, New York University) for MIC studies on clinical
isolates of MRSA and conducting the mouse model of staphylococcal
septicemia.
NR 62
TC 11
Z9 11
U1 0
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD FEB 13
PY 2014
VL 57
IS 3
BP 1063
EP 1078
DI 10.1021/jm401752p
PG 16
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AB0OW
UT WOS:000331493000037
PM 24450337
ER
PT J
AU Ferreyra, GA
Elinoff, JM
Demirkale, CY
Starost, MF
Buckley, M
Munson, PJ
Krakauer, T
Danner, RL
AF Ferreyra, Gabriela A.
Elinoff, Jason M.
Demirkale, Cumhur Y.
Starost, Matthew F.
Buckley, Marilyn
Munson, Peter J.
Krakauer, Teresa
Danner, Robert L.
TI Late Multiple Organ Surge in Interferon-Regulated Target Genes
Characterizes Staphylococcal Enterotoxin B Lethality
SO PLOS ONE
LA English
DT Article
ID TOXIC-SHOCK-SYNDROME; A STREPTOCOCCAL INFECTIONS; MONKEYS
MACACA-MULATTA; INNATE IMMUNE-RESPONSE; HUMAN T-CELLS; DENDRITIC CELLS;
I INTERFERON; BACTERIAL SUPERANTIGENS; INTRANASAL EXPOSURE;
ENDOTHELIAL-CELLS
AB Background: Bacterial superantigens are virulence factors that cause toxic shock syndrome. Here, the genome-wide, temporal response of mice to lethal intranasal staphylococcal enterotoxin B (SEB) challenge was investigated in six tissues.
Results: The earliest responses and largest number of affected genes occurred in peripheral blood mononuclear cells (PBMC), spleen, and lung tissues with the highest content of both T-cells and monocyte/macrophages, the direct cellular targets of SEB. In contrast, the response of liver, kidney, and heart was delayed and involved fewer genes, but revealed a dominant genetic program that was seen in all 6 tissues. Many of the 85 uniquely annotated transcripts participating in this shared genomic response have not been previously linked to SEB. Nine of the 85 genes were subsequently confirmed by RTPCR in every tissue/organ at 24 h. These 85 transcripts, up-regulated in all tissues, annotated to the interferon (IFN)/antiviralresponse and included genes belonging to the DNA/RNA sensing system, DNA damage repair, the immunoproteasome, and the ER/metabolic stress-response and apoptosis pathways. Overall, this shared program was identified as a type I and II interferon (IFN)-response and the promoters of these genes were highly enriched for IFN regulatory matrices. Several genes whose secreted products induce the IFN pathway were up-regulated at early time points in PBMCs, spleen, and/or lung. Furthermore, IFN regulatory factors including Irf1, Irf7 and Irf8, and Zbp1, a DNA sensor/transcription factor that can directly elicit an IFN innate immune response, participated in this host-wide SEB signature.
Conclusion: Global gene-expression changes across multiple organs implicated a host-wide IFN-response in SEB-induced death. Therapies aimed at IFN-associated innate immunity may improve outcome in toxic shock syndromes.
C1 [Ferreyra, Gabriela A.; Elinoff, Jason M.; Danner, Robert L.] NIH, Funct Genom & Prote Facil, Dept Crit Care Med, Clin Res Ctr, Bethesda, MD 20892 USA.
[Demirkale, Cumhur Y.; Munson, Peter J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Starost, Matthew F.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA.
[Buckley, Marilyn; Krakauer, Teresa] US Army Med Res Inst Infect Dis, Integrated Toxicol Div, Ft Detrick, MD 21702 USA.
RP Krakauer, T (reprint author), US Army Med Res Inst Infect Dis, Integrated Toxicol Div, Ft Detrick, MD 21702 USA.
EM teresa.krakauer@us.army.mil; rdanner@nih.gov
FU Defense Threat Reduction Agency [DTRA 3.10035]; Intramural Research
Program of the Critical Care Medicine Department, NIH Clinical Center
FX This research was entirely funded by The Defense Threat Reduction Agency
(#DTRA 3.10035) and the Intramural Research Program of the Critical Care
Medicine Department, NIH Clinical Center. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 84
TC 7
Z9 7
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 2014
VL 9
IS 2
AR e88756
DI 10.1371/journal.pone.0088756
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA7GP
UT WOS:000331266000062
PM 24551153
ER
PT J
AU Yin, HG
Kosa, P
Liu, XB
Swaim, WD
Lai, ZN
Cabrera-Perez, J
Di Pasquale, G
Ambudkar, IS
Bugge, TH
Chiorini, JA
AF Yin, Hongen
Kosa, Peter
Liu, Xibao
Swaim, William D.
Lai, Zhennan
Cabrera-Perez, Javier
Di Pasquale, Giovanni
Ambudkar, Indu S.
Bugge, Thomas H.
Chiorini, John A.
TI Matriptase Deletion Initiates a Sjogren's Syndrome-Like Disease in Mice
SO PLOS ONE
LA English
DT Article
ID SALIVARY-GLAND; NETHERTON-SYNDROME; TIGHT JUNCTION; ATOPIC-DERMATITIS;
EPITHELIAL-CELLS; TRANSGENIC MICE; EXPRESSION; GENE; MUTATIONS;
ICHTHYOSIS
AB Objective: The objective of this study was to determine the effect of epithelial barrier disruption, caused by deficiency of the membrane-anchored serine protease, matriptase, on salivary gland function and the induction of autoimmunity in an animal model.
Methods: Embryonic and acute ablation of matriptase expression in the salivary glands of mice was induced, leading to decreased epithelial barrier function. Mice were characterized for secretory epithelial function and the induction of autoimmunity including salivary and lacrimal gland dysfunction, lymphocytic infiltration, serum anti-Ro/SSA, anti-La/SSB and antinuclear antibodies. Salivary glands immune activation/regulation, barrier function as well as tight junction proteins expression also were determined. Expression of matriptase in minor salivary gland biopsies was compared among pSS patients and healthy volunteers.
Results: Embryonic ablation of matriptase expression in mice resulted in the loss of secretory epithelial cell function and the induction of autoimmunity similar to that observed in primary Sjogren's syndrome. Phenotypic changes included exocrine gland dysfunction, lymphocytic infiltrates, production of Sjogren's syndrome-specific autoantibodies, and overall activation of the immune system. Acute ablation of matriptase expression resulted in significant salivary gland dysfunction in the absence of overt immune activation. Analysis of the salivary glands indicates a loss of electrical potential across the epithelial layer as well as altered distribution of a tight junction protein. Moreover, a significant decrease in matriptase gene expression was detected in the minor salivary glands of pSS patients compared with healthy volunteers.
Conclusions: Our findings demonstrate that local impairment of epithelial barrier function can lead to loss of exocrine gland dysfunction in the absence of inflammation while systemic deletion can induce a primary Sjogren's syndrome like phenotype with autoimmunity and loss of gland function.
C1 [Yin, Hongen; Liu, Xibao; Swaim, William D.; Lai, Zhennan; Cabrera-Perez, Javier; Di Pasquale, Giovanni; Ambudkar, Indu S.; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
[Kosa, Peter; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
RP Yin, HG (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
EM yinho@mail.nih.gov; jchiorini@dir.nidcr.nih.gov
FU National Institutes of Health (NIH); National Institute of Dental and
Craniofacial Research (NIDCR) intramural grants
FX This work is supported by National Institutes of Health (NIH), National
Institute of Dental and Craniofacial Research (NIDCR) intramural grants
to JAC and THB. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 48
TC 5
Z9 5
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 13
PY 2014
VL 9
IS 2
AR e82852
DI 10.1371/journal.pone.0082852
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA7GP
UT WOS:000331266000001
PM 24551030
ER
PT J
AU Baker, SG
Kramer, BS
Lindeman, KS
AF Baker, Stuart G.
Kramer, Barnett S.
Lindeman, Karen S.
TI The Randomized Registry Trial
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Baker, Stuart G.; Kramer, Barnett S.] NIH, Bethesda, MD 20892 USA.
[Lindeman, Karen S.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
RP Baker, SG (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM sb16i@nih.gov
NR 5
TC 3
Z9 3
U1 1
U2 3
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 13
PY 2014
VL 370
IS 7
BP 681
EP 682
DI 10.1056/NEJMc1315677
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AA6CX
UT WOS:000331187500032
PM 24521130
ER
PT J
AU Fenalti, G
Giguere, PM
Katritch, V
Huang, XP
Thompson, AA
Cherezov, V
Roth, BL
Stevens, RC
AF Fenalti, Gustavo
Giguere, Patrick M.
Katritch, Vsevolod
Huang, Xi-Ping
Thompson, Aaron A.
Cherezov, Vadim
Roth, Bryan L.
Stevens, Raymond C.
TI Molecular control of delta-opioid receptor signalling
SO NATURE
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; X-RAY CRYSTALLOGRAPHY; SODIUM-IONS;
CRYSTALLIZING MEMBRANE; ALLOSTERIC REGULATION; LIPIDIC MESOPHASES;
INVERSE AGONISTS; ANTAGONISTS; DISCOVERY; BINDING
AB Opioids represent widely prescribed and abused medications, although their signal transduction mechanisms are not well understood. Here we present the 1.8 angstrom high-resolution crystal structure of the human delta-opioid receptor (delta-OR), revealing the presence and fundamental role of a sodium ion in mediating allosteric control of receptor functional selectivity and constitutive activity. The distinctive delta-OR sodium ion site architecture is centrally located in a polar interaction network in the seven-transmembrane bundle core, with the sodium ion stabilizing a reduced agonist affinity state, and thereby modulating signal transduction. Site-directed mutagenesis and functional studies reveal that changing the allosteric sodium site residue Asn 131 to an alanine or a valine augments constitutive beta-arrestin-mediated signalling. Asp95Ala, Asn310Ala and Asn314Ala mutations transform classical delta-opioid antagonists such as naltrindole into potent beta-arrestin-biased agonists. The data establish the molecular basis for allosteric sodium ion control in opioid signalling, revealing that sodium-coordinating residues act as 'efficacy switches' at a prototypic G-protein-coupled receptor.
C1 [Fenalti, Gustavo; Katritch, Vsevolod; Thompson, Aaron A.; Cherezov, Vadim; Stevens, Raymond C.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
[Giguere, Patrick M.; Huang, Xi-Ping; Roth, Bryan L.] Univ North Carolina Chapel Hill, Sch Med, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Chapel Hill, NC 27599 USA.
[Giguere, Patrick M.; Huang, Xi-Ping; Roth, Bryan L.] Univ North Carolina Chapel Hill, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Giguere, Patrick M.; Huang, Xi-Ping; Roth, Bryan L.] Univ North Carolina Chapel Hill, Sch Med, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
RP Stevens, RC (reprint author), Scripps Res Inst, Dept Integrat Struct & Computat Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM bryan_roth@med.unc.edu; stevens@scripps.edu
RI Roth, Bryan/F-3928-2010; Cherezov, Vadim/L-9812-2013; Katritch,
Vsevolod/Q-8357-2016; Stevens, Raymond/K-7272-2015
OI Cherezov, Vadim/0000-0002-5265-3914; Stevens,
Raymond/0000-0002-4522-8725
FU National Institutes of Health [P50 GM073197, U54 GM094618, R01
DA017204]; NIMH Psychoactive Drug Screening Program; Michael Hooker
Chair for Protein Therapeutics and Translational Proteomics; National
Cancer Institute [Y1-CO-1020]; National Institute of General Medical
Sciences [Y1-GM-1104]
FX This work was supported by the National Institutes of Health Common Fund
grant P50 GM073197 for technology development (V. C. and R. C. S.),
PSI:Biology grant U54 GM094618 for biological studies and structure
production (target GPCR-39) (V. K., V. C. and R. C. S.), R01 DA017204
and the NIMH Psychoactive Drug Screening Program (P. G., X.-P. H., B. L.
R.) and the Michael Hooker Chair for Protein Therapeutics and
Translational Proteomics to B. L. R. We thank J. Velasquez for help with
molecular biology, T. Trinh and M. Chu for help with baculovirus
expression, G. W. Han for help with structure analysis and quality
control review, E. Abola for help with sodium site analysis, A. Walker
for assistance with manuscript preparation and J. Smith, R. Fischetti
and N. Sanishvili for assistance in development and use of the minibeam
and beamtime at beamline 23-ID at the Advanced Photon Source, which is
supported by National Cancer Institute grant Y1-CO-1020 and National
Institute of General Medical Sciences grant Y1-GM-1104.
NR 46
TC 135
Z9 137
U1 3
U2 68
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 13
PY 2014
VL 506
IS 7487
BP 191
EP 196
DI 10.1038/nature12944
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700031
PM 24413399
ER
PT J
AU Smith, AA
Kepka, D
Yabroff, KR
AF Smith, Alexandria A.
Kepka, Deanna
Yabroff, K. Robin
TI Advanced practice registered nurses, physician assistants and cancer
prevention and screening: a systematic review
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Review
ID HEALTH-CARE PROVIDERS; CERVICAL-CANCER; UNITED-STATES; FOLLOW-UP;
PRACTITIONERS; SERVICES; WOMEN; DISPARITIES; PATTERNS; OVERUSE
AB Background: For more than two decades, integration of team-based approaches in primary care, including physicians, advanced practice registered nurses and physician assistants (APRN/PA), have been recommended for improving healthcare delivery, yet little is known about their roles in cancer screening and prevention. This study aims to review the current literature on the participation and roles of APRN/PAs in providing cancer screening and prevention recommendations in primary care settings in the United States.
Methods: We searched MEDLINE and CINAHL to identify studies published in 1990-2011 reporting on cervical, breast, and colorectal cancer screening and smoking cessation, diet, and physical activity recommendations by APRN/PAs in the United States. A total of 15 studies met all of our eligibility criteria. Key study, provider, and patient characteristics were abstracted as were findings about APRN/PA recommendations for screening and prevention.
Results: Most studies were cross-sectional, showed results from within a single city or state, had relatively small sample sizes, reported non-standardized outcome measures. Few studies reported any patient characteristics. APRN/PAs are involved in recommending cancer screening and prevention, although we found variation across screening tests and health behavior recommendations.
Conclusions: Additional research on the cancer prevention and screening practices of APRN/PAs in primary care settings using standardized outcome measures in relation to evidence-based guidelines may help strengthen primary care delivery in the United States.
C1 [Smith, Alexandria A.] Amer Legacy Fdn, Washington, DC USA.
[Kepka, Deanna; Yabroff, K. Robin] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Kepka, Deanna] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA.
[Kepka, Deanna] Huntsman Canc Inst, Salt Lake City, UT USA.
RP Kepka, D (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM deanna.Kepka@hci.utah.edu
OI Yabroff, K. Robin/0000-0003-0644-5572
NR 44
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 1472-6963
J9 BMC HEALTH SERV RES
JI BMC Health Serv. Res.
PD FEB 12
PY 2014
VL 14
AR 68
DI 10.1186/1472-6963-14-68
PG 14
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA AC6DJ
UT WOS:000332611300001
PM 24521264
ER
PT J
AU Wu, XS
Wu, LG
AF Wu, Xin-Sheng
Wu, Ling-Gang
TI The Yin and Yang of Calcium Effects on Synaptic Vesicle Endocytosis
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE calcium; endocytosis
ID FROG NEUROMUSCULAR-JUNCTION; ADRENAL CHROMAFFIN CELLS; KISS-AND-RUN;
NEUROTRANSMITTER RELEASE; AFFERENT SYNAPSE; NERVE-TERMINALS; TRAPEZOID
BODY; MEDIAL NUCLEUS; CNS SYNAPSE; CA2+
AB A large number of studies suggest that calcium triggers and accelerates vesicle endocytosis at many synapses and non-neuronal secretory cells. However, many studies show that prolonging the duration of the stimulation train, which induces more calcium influx, slows down endocytosis; and several studies suggest that instead of triggering endocytosis, calcium actually inhibits endocytosis. Here we addressed this apparent conflict at a large nerve terminal, the calyx of Held in rat brainstem, in which recent studies suggest that transient calcium increase up to tens of micromolar concentration at the micro/nano domain triggers endocytosis. By dialyzing 0-1 mu M calcium into the calyx via a whole-cell pipette, we found that slow endocytosis was inhibited by calcium dialysis in a concentration-dependent manner. Thus, prolonged, small, and global calcium increase inhibits endocytosis, whereas transient and large calcium increase at the micro/nano domain triggers endocytosis and facilitates endocytosis. This yin and yang effect of calcium may reconcile apparent conflicts regarding whether calcium accelerates or inhibits endocytosis. Whether endocytosis is fast or slow depends on the net outcome between the yin and yang effect of calcium.
C1 [Wu, Xin-Sheng; Wu, Ling-Gang] NINDS, Bethesda, MD 20892 USA.
RP Wu, LG (reprint author), NINDS, 35 Convent Dr,Bldg 35,Room 2B-1012, Bethesda, MD 20892 USA.
EM wul@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke Intramural
Research Program
FX This work was supported by the National Institute of Neurological
Disorders and Stroke Intramural Research Program. We thank Drs. Fujun
Luo, Jiansong Sheng, and Zhen Zhang for critical reading of this
manuscript.
NR 49
TC 11
Z9 11
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 12
PY 2014
VL 34
IS 7
BP 2652
EP 2659
DI 10.1523/JNEUROSCI.3582-13.2014
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA AB2HV
UT WOS:000331614700026
PM 24523554
ER
PT J
AU Gazzinelli, RT
Mendonca-Neto, R
Lilue, J
Howard, J
Sher, A
AF Gazzinelli, Ricardo T.
Mendonca-Neto, Rondon
Lilue, Jingtao
Howard, Jonathan
Sher, Alan
TI Innate Resistance against Toxoplasma gondii: An Evolutionary Tale of
Mice, Cats, and Men
SO CELL HOST & MICROBE
LA English
DT Review
ID TOLL-LIKE RECEPTORS; DENDRITIC CELLS; INFECTION; PROFILIN; IMMUNITY;
MECHANISM; MONOCYTES; VIRULENCE; PROTEIN; GTPASES
AB Recent studies have revealed remarkable species specificity of the Toll-like receptors (TLRs) TLR11 and TLR12 and the immunity-related GTPase (IRG) proteins that are essential elements for detection and immune control of Toxoplasma gondii in mice, but not in humans. The biological and evolutionary implications of these findings for the T. gondii host-pathogen relationship and for human disease are discussed.
C1 [Gazzinelli, Ricardo T.] Oswaldo Cruz Fdn Minas Gerais, Rene Rachou Inst, Immunopathol Lab, BR-30190002 Belo Horizonte, MG, Brazil.
[Gazzinelli, Ricardo T.; Mendonca-Neto, Rondon] Univ Fed Minas Gerais, Inst Biol Sci, Dept Biochem & Immunol, BR-31270901 Belo Horizonte, MG, Brazil.
[Gazzinelli, Ricardo T.] Univ Massachusetts Med Sch, Div Infect Dis & Immunol, Worcester, MA 01605 USA.
[Lilue, Jingtao; Howard, Jonathan] Univ Cologne, Inst Genet, D-50674 Cologne, Germany.
[Howard, Jonathan] Inst Gulbenkian Ciencias, P-2780156 Oeiras, Portugal.
[Sher, Alan] NIAID, Lab Parasit Dis, NIH, Bethesda, MD 20892 USA.
RP Gazzinelli, RT (reprint author), Oswaldo Cruz Fdn Minas Gerais, Rene Rachou Inst, Immunopathol Lab, BR-30190002 Belo Horizonte, MG, Brazil.
EM ritoga@cpqrr.fiocruz.br; jhoward@igc.gulbenkian.pt; asher@niaid.nih.gov
OI Lilue, Jingtao/0000-0002-1958-0231
FU CAPES; David Rockefeller Center for Latin America Studies at the Harvard
School of Public Health; National Institute of Science and Technology on
Vaccines; National Institutes of Health [NIAID R01 AI071319-01]; German
Research Council [SPP1399, SFB670, SFB680]; Intramural Program of the
National Institutes of Allergy and Infectious Disease
FX The authors apologize for not citing many of the important references
that have contributed to this review owing to space limitations. We are
grateful to the members of our laboratories as well as Sankar Ghosh,
Greg Taylor, and Felix Yarovinsky for important discussions and their
key contributions in defining the role of TLR11, TLR12, and IRG proteins
in mouse resistance to T. gondii. We also thank Daniel Caffrey and
Warrison Andrade for critically reading this manuscript and for
discussions. R.T.G. is recipient of the Visiting Professor Scholarship
from CAPES and the David Rockefeller Center for Latin America Studies at
the Harvard School of Public Health and is supported by the National
Institute of Science and Technology on Vaccines and the National
Institutes of Health (NIAID R01 AI071319-01). J.H. is recipient of the
SPP1399, SFB670, and SFB680 grants from the German Research Council,
while A.S. is supported by the Intramural Program of the National
Institutes of Allergy and Infectious Disease.
NR 25
TC 17
Z9 17
U1 2
U2 18
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 12
PY 2014
VL 15
IS 2
BP 132
EP 138
DI 10.1016/j.chom.2014.01.004
PG 7
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AB0IT
UT WOS:000331475900004
PM 24528860
ER
PT J
AU Campa, D
Barrdahl, M
Tsilidis, KK
Severi, G
Diver, WR
Siddiq, A
Chanock, S
Hoover, RN
Ziegler, RG
Berg, CD
Buys, SS
Haiman, CA
Henderson, BE
Schumacher, FR
Le Marchand, L
Flesch-Janys, D
Lindstrom, S
Hunter, DJ
Hankinson, SE
Willett, WC
Kraft, P
Cox, DG
Khaw, KT
Tjonneland, A
Dossus, L
Trichopoulos, D
Panico, S
van Gils, CH
Weiderpass, E
Barricarte, A
Sund, M
Gaudet, MM
Giles, G
Southey, M
Baglietto, L
Chang-Claude, J
Kaaks, R
Canzian, F
AF Campa, Daniele
Barrdahl, Myrto
Tsilidis, Konstantinos K.
Severi, Gianluca
Diver, W. Ryan
Siddiq, Afshan
Chanock, Stephen
Hoover, Robert N.
Ziegler, Regina G.
Berg, Christine D.
Buys, Saundra S.
Haiman, Christopher A.
Henderson, Brian E.
Schumacher, Fredrick R.
Le Marchand, Loic
Flesch-Janys, Dieter
Lindstroem, Sara
Hunter, David J.
Hankinson, Susan E.
Willett, Walter C.
Kraft, Peter
Cox, David G.
Khaw, Kay-Tee
Tjonneland, Anne
Dossus, Laure
Trichopoulos, Dimitrios
Panico, Salvatore
van Gils, Carla H.
Weiderpass, Elisabete
Barricarte, Aurelio
Sund, Malin
Gaudet, Mia M.
Giles, Graham
Southey, Melissa
Baglietto, Laura
Chang-Claude, Jenny
Kaaks, Rudolf
Canzian, Federico
TI A Genome-Wide "Pleiotropy Scan'' Does Not Identify New Susceptibility
Loci for Estrogen Receptor Negative Breast Cancer
SO PLOS ONE
LA English
DT Article
ID COMPLEX DISEASES; ASSOCIATION; TRAITS; RISK; METAANALYSIS
AB Approximately 15-30% of all breast cancer tumors are estrogen receptor negative (ER-). Compared with ER- positive (ER+) disease they have an earlier age at onset and worse prognosis. Despite the vast number of risk variants identified for numerous cancer types, only seven loci have been unambiguously identified for ER- negative breast cancer. With the aim of identifying new susceptibility SNPs for this disease we performed a pleiotropic genome-wide association study (GWAS). We selected 3079 SNPs associated with a human complex trait or disease at genome-wide significance level (P<5x10(-8)) to perform a secondary analysis of an ER- negative GWAS from the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), including 1998 cases and 2305 controls from prospective studies. We then tested the top ten associations (i.e. with the lowest P-values) using three additional populations with a total sample size of 3509 ER+ cases, 2543 ER- cases and 7031 healthy controls. None of the 3079 selected variants in the BPC3 ER- GWAS were significant at the adjusted threshold. 186 variants were associated with ER- breast cancer risk at a conventional threshold of P<0.05, with P-values ranging from 0.049 to 2.3 x 10(-4). None of the variants reached statistical significance in the replication phase. In conclusion, this study did not identify any novel susceptibility loci for ER-breast cancer using a "pleiotropic approach''.
C1 [Campa, Daniele; Barrdahl, Myrto; Chang-Claude, Jenny; Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Tsilidis, Konstantinos K.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England.
[Tsilidis, Konstantinos K.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
[Severi, Gianluca; Giles, Graham; Southey, Melissa; Baglietto, Laura] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia.
[Severi, Gianluca; Giles, Graham; Southey, Melissa; Baglietto, Laura] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Sch Populat Hlth, Melbourne, Vic 3010, Australia.
[Diver, W. Ryan; Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Siddiq, Afshan; Cox, David G.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Chanock, Stephen; Hoover, Robert N.; Ziegler, Regina G.; Berg, Christine D.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Buys, Saundra S.] Univ Utah, Sch Med, Div Oncol, Huntsman Canc Inst, Salt Lake City, UT USA.
[Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick R.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Flesch-Janys, Dieter] Univ Med Ctr Hamburg Eppendorf, Dept Med Biometr & Epidemiol, Hamburg, Germany.
[Lindstroem, Sara; Hunter, David J.; Hankinson, Susan E.; Willett, Walter C.; Kraft, Peter; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Hankinson, Susan E.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA USA.
[Hankinson, Susan E.] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
[Cox, David G.] Univ Lyon 1, F-69365 Lyon, France.
[Cox, David G.] Ctr Rech Cancerol Lyon, Inst Natl Sante & Rech Med, U1052, Lyon, France.
[Cox, David G.] Ctr Rech Cancerol Lyon, Ctr Natl Rech Sci, UMR5286, Lyon, France.
[Cox, David G.] Ctr Leon Berard, F-69373 Lyon, France.
[Khaw, Kay-Tee] Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England.
[Tjonneland, Anne] Danish Canc Soc, Res Ctr, Copenhagen, Denmark.
[Dossus, Laure] Hormones & Womens Hlth Team, Inst Natl Sante & Rech Med, Ctr Res Epidemiol & Populat Hlth, Villejuif, France.
[Dossus, Laure] Univ Paris 11, UMRS 1018, Villejuif, France.
[Dossus, Laure] Inst Gustave Roussy, F-94805 Villejuif, France.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Trichopoulos, Dimitrios] Hellen Hlth Fdn, Athens, Greece.
[Panico, Salvatore] Univ Naples Federico II, Dipartimento Med Clin & Chirurg, Naples, Italy.
[van Gils, Carla H.] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Weiderpass, Elisabete] Arctic Univ Tromso, Dept Community Med, Fac Hlth Sci, Univ Tromso, Tromso, Norway.
[Weiderpass, Elisabete] Canc Registry Norway, Dept Res, Oslo, Norway.
[Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Weiderpass, Elisabete] Samfundet Folkhalsan, Helsinki, Finland.
[Barricarte, Aurelio] Navarre Publ Hlth Inst, Pamplona, Spain.
[Barricarte, Aurelio] CIBERESP, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain.
[Sund, Malin] Umea Univ Hosp, Dept Surg, S-90185 Umea, Sweden.
[Canzian, Federico] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany.
RP Campa, D (reprint author), German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
EM d.campa@dkfz.de
RI Berg , Christine/K-1047-2014; Campa, Daniele/K-1617-2016; Weiderpass,
Elisabete/M-4029-2016; Cox, David/A-2023-2009; Panico,
Salvatore/K-6506-2016;
OI Campa, Daniele/0000-0003-3220-9944; Weiderpass,
Elisabete/0000-0003-2237-0128; Cox, David/0000-0002-2152-9259; Panico,
Salvatore/0000-0002-5498-8312; Giles, Graham/0000-0003-4946-9099
FU US National Institutes of Health, National Cancer Institute
[U01-CA98233-07, U01CA98710-06, U01-CA98216-06, U01-CA98758-07];
Intramural Research Program of National Institutes of Health; National
Cancer Institute, Division of Cancer Epidemiology and Genetics
FX This work was supported by the US National Institutes of Health,
National Cancer Institute (cooperative agreements U01-CA98233-07 to
D.J.H.; U01CA98710-06 to M.J.T.; U01-CA98216-06 to E.R. and R.K.; and
U01-CA98758-07 to B.E.H.); and Intramural Research Program of National
Institutes of Health and National Cancer Institute, Division of Cancer
Epidemiology and Genetics. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 30
TC 6
Z9 6
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 11
PY 2014
VL 9
IS 2
AR e85955
DI 10.1371/journal.pone.0085955
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA7DT
UT WOS:000331258100006
PM 24523857
ER
PT J
AU Fletcher, CV
Staskus, K
Wietgrefe, SW
Rothenberger, M
Reilly, C
Chipman, JG
Beilman, GJ
Khoruts, A
Thorkelson, A
Schmidt, TE
Anderson, J
Perkey, K
Stevenson, M
Perelson, AS
Douek, DC
Haase, AT
Schacker, TW
AF Fletcher, Courtney V.
Staskus, Kathryn
Wietgrefe, Stephen W.
Rothenberger, Meghan
Reilly, Cavan
Chipman, Jeffrey G.
Beilman, Greg J.
Khoruts, Alexander
Thorkelson, Ann
Schmidt, Thomas E.
Anderson, Jodi
Perkey, Katherine
Stevenson, Mario
Perelson, Alan S.
Douek, Daniel C.
Haase, Ashley T.
Schacker, Timothy W.
TI Persistent HIV-1 replication is associated with lower antiretroviral
drug concentrations in lymphatic tissues
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE drug levels; pharmacokinetics; FDC network
ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL-ACTIVATION; LYMPHOID-TISSUES;
PROTEASE INHIBITOR; INFECTED PATIENTS; RALTEGRAVIR INTENSIFICATION;
IMMUNE RECONSTITUTION; DENDRITIC CELLS; UNITED-STATES; THERAPY
AB Antiretroviral therapy can reduce HIV-1 to undetectable levels in peripheral blood, but the effectiveness of treatment in suppressing replication in lymphoid tissue reservoirs has not been determined. Here we show in lymph node samples obtained before and during 6 mo of treatment that the tissue concentrations of five of the most frequently used antiretroviral drugs are much lower than in peripheral blood. These lower concentrations correlated with continued virus replication measured by the slower decay or increases in the follicular dendritic cell network pool of virions and with detection of viral RNA in productively infected cells. The evidence of persistent replication associated with apparently suboptimal drug concentrations argues for development and evaluation of novel therapeutic strategies that will fully suppress viral replication in lymphatic tissues. These strategies could avert the long-term clinical consequences of chronic immune activation driven directly or indirectly by low-level viral replication to thereby improve immune reconstitution.
C1 [Fletcher, Courtney V.] Univ Nebraska Med Ctr, Dept Pharm Practice, Coll Pharm, Omaha, NE USA.
[Staskus, Kathryn; Wietgrefe, Stephen W.; Perkey, Katherine; Haase, Ashley T.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA.
[Rothenberger, Meghan; Khoruts, Alexander; Thorkelson, Ann; Schmidt, Thomas E.; Anderson, Jodi; Schacker, Timothy W.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Reilly, Cavan] Univ Minnesota, Dept Biostat, Minneapolis, MN 55455 USA.
[Chipman, Jeffrey G.; Beilman, Greg J.] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA.
[Stevenson, Mario] Univ Miami, Dept Med, Miami, FL 33136 USA.
[Perelson, Alan S.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
[Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Schacker, TW (reprint author), Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA.
EM schacker@umn.edu
OI Chipman, Jeffrey/0000-0002-0759-3705; Beilman,
Gregory/0000-0001-5036-3027
FU National Institutes of Health [AI074340, AI028433]
FX We thank Lisa Turnquist, Colleen O'Neil, and Tim Leonard for their
contributions. Methods for IC and tissue assessment of drug
concentration were developed in the C.V.F. laboratory by C.V.F., Dr.
Brian L. Robbins, and Mr. Lee Winchester. This work was supported in
part by National Institutes of Health Grants AI074340 and AI028433.
NR 55
TC 150
Z9 150
U1 3
U2 24
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 11
PY 2014
VL 111
IS 6
BP 2307
EP 2312
DI 10.1073/pnas.1318249111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA3NO
UT WOS:000330999600058
PM 24469825
ER
PT J
AU Griner, LAM
Guha, R
Shinn, P
Young, RM
Keller, JM
Liu, D
Goldlust, IS
Yasgar, A
McKnight, C
Boxer, MB
Duveau, DY
Jiang, JK
Michael, S
Mierzwa, T
Huang, W
Walsh, MJ
Mott, BT
Patela, P
Leister, W
Maloney, DJ
Leclair, CA
Rai, G
Jadhav, A
Peyser, BD
Austin, CP
Martin, SE
Simeonov, A
Ferrer, M
Staudt, LM
Thomas, CJ
AF Griner, Lesley A. Mathews
Guha, Rajarshi
Shinn, Paul
Young, Ryan M.
Keller, Jonathan M.
Liu, Dongbo
Goldlust, Ian S.
Yasgar, Adam
McKnight, Crystal
Boxer, Matthew B.
Duveau, Damien Y.
Jiang, Jian-Kang
Michael, Sam
Mierzwa, Tim
Huang, Wenwei
Walsh, Martin J.
Mott, Bryan T.
Patela, Paresma
Leister, William
Maloney, David J.
Leclair, Christopher A.
Rai, Ganesha
Jadhav, Ajit
Peyser, Brian D.
Austin, Christopher P.
Martin, Scott E.
Simeonov, Anton
Ferrer, Marc
Staudt, Louis M.
Thomas, Craig J.
TI High-throughput combinatorial screening identifies drugs that cooperate
with ibrutinib to kill activated B-cell-like diffuse large B-cell
lymphoma cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE translational research; PCI-32765; Imbruvica
ID NF-KAPPA-B; ANTITUMOR-ACTIVITY; IN-VIVO; INHIBITOR; CANCER;
COMBINATIONS; MALIGNANCIES; MUTATIONS; THERAPY; PATHWAY
AB The clinical development of drug combinations is typically achieved through trial-and-error or via insight gained through a detailed molecular understanding of dysregulated signaling pathways in a specific cancer type. Unbiased small-molecule combination (matrix) screening represents a high-throughput means to explore hundreds and even thousands of drug-drug pairs for potential investigation and translation. Here, we describe a high-throughput screening platform capable of testing compounds in pairwise matrix blocks for the rapid and systematic identification of synergistic, additive, and antagonistic drug combinations. We use this platform to define potential therapeutic combinations for the activated B-cell-like subtype (ABC) of diffuse large B-cell lymphoma (DLBCL). We identify drugs with synergy, additivity, and antagonism with the Bruton's tyrosine kinase inhibitor ibrutinib, which targets the chronic active B-cell receptor signaling that characterizes ABC DLBCL. Ibrutinib interacted favorably with a wide range of compounds, including inhibitors of the PI3K-AKT- mammalian target of rapamycin signaling cascade, other B-cell receptor pathway inhibitors, Bcl-2 family inhibitors, and several components of chemotherapy that is the standard of care for DLBCL.
C1 [Griner, Lesley A. Mathews; Guha, Rajarshi; Shinn, Paul; Keller, Jonathan M.; Liu, Dongbo; Goldlust, Ian S.; Yasgar, Adam; McKnight, Crystal; Boxer, Matthew B.; Duveau, Damien Y.; Jiang, Jian-Kang; Michael, Sam; Mierzwa, Tim; Huang, Wenwei; Walsh, Martin J.; Mott, Bryan T.; Patela, Paresma; Leister, William; Maloney, David J.; Leclair, Christopher A.; Rai, Ganesha; Jadhav, Ajit; Austin, Christopher P.; Martin, Scott E.; Simeonov, Anton; Ferrer, Marc; Thomas, Craig J.] NCI, Div Preclin Innovat, NIH, Chem Genom Ctr,Natl Ctr Advancing Translat Sci, Bethesda, MD 20892 USA.
[Young, Ryan M.; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Peyser, Brian D.] NCI, Dev Therapeut Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Patela, Paresma] SAIC Frederick Inc, Basic Sci Program, Biol Chem Lab, Frederick Natl Lab Canc Res, Ft Detrick, MD 21702 USA.
RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM lstaudt@mail.nih.gov; craigt@mail.nih.gov
OI Peyser, Brian/0000-0002-3455-5181
FU Division of Preclinical Innovation, National Center for Advancing
Translational Sciences; Molecular Libraries Initiative of the National
Institutes of Health Roadmap for Medical Research; Intramural Research
Program of the National Human Genome Research Institute; Intramural
Research Program of the National Cancer Institute, Center for Cancer
Research; Frederick National Laboratory for Cancer Research, National
Institutes of Health [HHSN261200800001E, U54CA143930]
FX We thank Drs. Jack Taunton, Shaomeng Wang, Fed Bernal, James E. Bradner,
Benjamin F. Cravatt, Daniel K. Nomura, Mark Tebbe, and Kenneth Bair for
kind donations to the MIPE compound library. This work was supported by
the Division of Preclinical Innovation, National Center for Advancing
Translational Sciences; the Molecular Libraries Initiative of the
National Institutes of Health Roadmap for Medical Research; the
Intramural Research Program of the National Human Genome Research
Institute; and the Intramural Research Program of the National Cancer
Institute, Center for Cancer Research and the Frederick National
Laboratory for Cancer Research, National Institutes of Health, including
Contract HHSN261200800001E and Grant U54CA143930.
NR 52
TC 58
Z9 58
U1 2
U2 25
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 11
PY 2014
VL 111
IS 6
BP 2349
EP 2354
DI 10.1073/pnas.1311846111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA3NO
UT WOS:000330999600065
ER
PT J
AU Bittencourt, MS
Blaha, MJ
Blankstein, R
Budoff, M
Vargas, JD
Blumenthal, RS
Agatston, AS
Nasir, K
AF Bittencourt, Marcio Sommer
Blaha, Michael J.
Blankstein, Ron
Budoff, Matthew
Vargas, Jose D.
Blumenthal, Roger S.
Agatston, Arthur S.
Nasir, Khurram
TI Polypill Therapy, Subclinical Atherosclerosis, and Cardiovascular
Events-Implications for the Use of Preventive Pharmacotherapy
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE polypill; risk stratification; subclinical atherosclerosis
ID CORONARY-ARTERY CALCIFICATION; ALL-CAUSE MORTALITY; POPULATION-BASED
COHORT; C-REACTIVE PROTEIN; RISK-FACTORS; DOUBLE-BLIND; DISEASE;
CALCIUM; INDIVIDUALS; PREDICTION
AB Objectives This study examines whether the coronary artery calcium (CAC) score can be used to define the target population to treat with a polypill.
Background Prior studies have suggested a single polypill to reduce cardiovascular disease (CVD) at the population level.
Methods Participants from MESA (Multi-Ethnic Study of Atherosclerosis) were stratified using the criteria of 4 polypill studies (TIPS [The Indian Polycap Study], Poly-Iran, Wald, and the PILL [Program to Improve Life and Longevity] Collaboration). We compared coronary heart disease (CHD) and CVD event rates and calculated the 5-year number needed to treat (NNT) after stratification based on the CAC score.
Results Among MESA participants eligible for TIPS, Poly-Iran, Wald, and the PILL Collaboration, CAC 0 was observed in 58.6%, 54.5%, 38.9%, and 40.8%, respectively. The rate of CHD events among those with CAC 0 varied from 1.2 to 1.9 events per 1,000 person-years, those with CAC scores from 1 to 100 had event rates ranging from 4.1 to 5.5, and in those with CAC scores > 100 the event rate ranged from 11.6 to 13.3. The estimated 5-year NNT to prevent 1 CVD event ranged from 81-130 for patients with CAC 0, 38-54 for those with CAC scores from 1 to 100, and 18-20 for those with CAC scores > 100.
Conclusions In MESA, among individuals eligible for treatment with the polypill, the majority of CHD and CVD events occurred in those with CAC scores > 100. The group with CAC 0 had a very low event rate and a high projected NNT. The avoidance of treatment in individuals with CAC 0 could allow for significant reductions in the population considered for treatment, with a more selective use of the polypill and, as a result, avoidance of treatment in those who are unlikely to benefit. (J Am Coll Cardiol 2014; 63: 434-43) (c) 2014 by the American College of Cardiology Foundation
C1 [Bittencourt, Marcio Sommer; Blankstein, Ron] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA.
[Bittencourt, Marcio Sommer; Blankstein, Ron] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Bittencourt, Marcio Sommer; Blankstein, Ron] Harvard Univ, Sch Med, Boston, MA USA.
[Blaha, Michael J.; Blumenthal, Roger S.; Nasir, Khurram] Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Baltimore, MD USA.
[Budoff, Matthew] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Div Cardiol, Torrance, CA 90509 USA.
[Vargas, Jose D.] Johns Hopkins Univ Hosp, Cardiol Div, Baltimore, MD 21287 USA.
[Vargas, Jose D.] NIH, Bethesda, MD 20892 USA.
[Agatston, Arthur S.; Nasir, Khurram] Baptist Hlth Med Grp, Ctr Prevent & Wellness Res, Miami Beach, FL 33139 USA.
[Agatston, Arthur S.; Nasir, Khurram] Florida Int Univ, Dept Med, Herbert Wertheim Coll Med, Miami, FL 33199 USA.
[Nasir, Khurram] Florida Int Univ, Dept Epidemiol, Robert Stempel Coll Publ Hlth, Miami, FL 33199 USA.
[Nasir, Khurram] Baptist Hlth South Florida, Baptist Cardiovasc Inst, Miami, FL USA.
RP Nasir, K (reprint author), Baptist Hlth Med Grp, Ctr Prevent & Wellness Res, 1691 Michigan Ave,Suite 500, Miami Beach, FL 33139 USA.
EM knasir1@jhmi.edu
RI Bittencourt, Marcio/C-1444-2011
OI Bittencourt, Marcio/0000-0002-3711-1754
FU NCATS NIH HHS [UL1 TR001079]; NHLBI NIH HHS [L30 HL110027]
NR 30
TC 33
Z9 33
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 11
PY 2014
VL 63
IS 5
BP 434
EP 443
DI 10.1016/j.jacc.2013.08.1640
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 304BX
UT WOS:000330721800006
PM 24161320
ER
PT J
AU Shuch, B
Vourganti, S
Ricketts, CJ
Middleton, L
Peterson, J
Merino, MJ
Metwalli, AR
Srinivasan, R
Linehan, WM
AF Shuch, Brian
Vourganti, Srinivas
Ricketts, Christopher J.
Middleton, Lindsay
Peterson, James
Merino, Maria J.
Metwalli, Adam R.
Srinivasan, Ramaprasad
Linehan, W. Marston
TI Defining Early-Onset Kidney Cancer: Implications for Germline and
Somatic Mutation Testing and Clinical Management
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RENAL-CELL CARCINOMA; HOGG-DUBE-SYNDROME; HEREDITARY LEIOMYOMATOSIS;
GENETIC-BASIS; YOUNG-ADULTS; TRANSLOCATION; DISEASE; CHILDREN; SPECTRUM
AB Purpose Approximately 5% to 8% of renal cell carcinoma (RCC) is hereditary. No guidelines exist for patient selection for RCC germline mutation testing. We evaluate how age of onset could indicate the need for germline mutation testing for detection of inherited forms of kidney cancer.
Patients and Methods We analyzed the age distribution of RCC cases in the SEER-17 program and in our institutional hereditary kidney cancer population. The age distributions were compared by sex, race, histology, and hereditary cancer syndrome. Models were established to evaluate the specific age thresholds for genetic testing.
Results The median age of patients with RCC in SEER-17 was 64 years, with the distribution closely approaching normalcy. Statistical differences were observed by race, sex, and subtype (P < .05). The bottom decile cutoff was 46 years of age and slightly differed by sex, race, and histology. The mean and median ages at presentation of 608 patients with hereditary kidney cancer were 39.3 years and 37 years, respectively. Although age varied by specific syndrome, 70% of these cases were found to lie at or below the bottom age decile. Modeling age-based genetic testing thresholds demonstrated that the 10th percentile maximized sensitivity and specificity.
Conclusion Early age of onset might be a sign of hereditary RCC. Even in the absence of clinical manifestations and personal/family history, an age of onset of 46 years or younger should trigger consideration for genetic counseling/germline mutation testing and may serve as a useful cutoff when establishing genetic testing guidelines. (C) 2013 by American Society of Clinical Oncology
C1 [Shuch, Brian; Vourganti, Srinivas; Ricketts, Christopher J.; Middleton, Lindsay; Peterson, James; Merino, Maria J.; Metwalli, Adam R.; Srinivasan, Ramaprasad; Linehan, W. Marston] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, NIH, CRC, 10 Ctr Dr,MSC 1107,Bldg 10,Room 1-5848, Bethesda, MD 20892 USA.
EM linehanm@mail.nih.gov
FU National Institutes of Health [ZIA1BC011028-05, ZIA BC011038-05, ZIA
BC011043-05, ZID BC011089-05, ZIE BC 011023-05]
FX Supported by Grants No. ZIA1BC011028-05, ZIA BC011038-05, ZIA
BC011043-05, ZID BC011089-05, and ZIE BC 011023-05 from the National
Institutes of Health.
NR 28
TC 17
Z9 17
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 10
PY 2014
VL 32
IS 5
BP 431
EP 437
DI 10.1200/JCO.2013.50.8192
PG 7
WC Oncology
SC Oncology
GA AA7AS
UT WOS:000331250100014
PM 24378414
ER
PT J
AU Roschewski, M
Stetler-Stevenson, M
Yuan, C
Mailankody, S
Korde, N
Landgren, O
AF Roschewski, Mark
Stetler-Stevenson, Maryalice
Yuan, Constance
Mailankody, Sham
Korde, Neha
Landgren, Ola
TI Minimal Residual Disease: What Are the Minimum Requirements?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID STEM-CELL TRANSPLANTATION; MULTIPLE-MYELOMA; COMPLETE RESPONSE;
FLOW-CYTOMETRY; HETEROGENEITY; DEXAMETHASONE; LENALIDOMIDE; COMBINATION;
EXPRESSION; SURVIVAL
C1 [Roschewski, Mark; Stetler-Stevenson, Maryalice; Yuan, Constance; Mailankody, Sham; Korde, Neha; Landgren, Ola] NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Roschewski, M (reprint author), NIH, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
NR 14
TC 7
Z9 7
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 10
PY 2014
VL 32
IS 5
BP 475
EP 476
DI 10.1200/JCO.2013.52.1955
PG 2
WC Oncology
SC Oncology
GA AA7AS
UT WOS:000331250100021
PM 24419126
ER
PT J
AU Su, XL
Dong, C
Zhang, JL
Su, LY
Wang, XM
Cui, HW
Chen, Z
AF Su, Xiulan
Dong, Chao
Zhang, Jialing
Su, Liya
Wang, Xuemei
Cui, Hongwei
Chen, Zhong
TI Combination therapy of anti-cancer bioactive peptide with Cisplatin
decreases chemotherapy dosing and toxicity to improve the quality of
life in xenograft nude mice bearing human gastric cancer
SO CELL AND BIOSCIENCE
LA English
DT Article
DE Anti-cancer bioactive peptide (ACBP); Cisplatin; Tumor growth; Quality
of life; Gastric cancer
ID BCL-2 FAMILY PROTEINS; CYTOCHROME-C; CELL-DEATH; APOPTOSIS; TRIAL;
PATHWAY; BAX
AB Background: A great challenge of cancer chemotherapy is to eliminate cancer cells and concurrently maintain the quality of life (QOL) for cancer patients. Previously, we identified a novel anti-cancer bioactive peptide (ACBP), a peptide induced in goat spleen or liver following immunization with human gastric cancer protein extract. ACBP alone exhibited anti-tumor activity without measurable side effects. Thus, we hypothesize that ACBP and combined chemotherapy could improve the efficacy of treatment and lead to a better QOL.
Results: In this study, ACBP was isolated and purified from immunized goat liver, and designated as ACBP-L. The anti-tumor activity was investigated in a previously untested human gastric cancer MGC-803 cell line and tumor model. ACBP-L inhibited cell proliferation in vitro in a dose and time dependent manner, titrated by MTT assay. The effect of ACBP-L on cell morphology was observed through light and scanning electron microscopy. In vivo ACBP-L alone significantly inhibited MGC-803 tumor growth in a xenograft nude mouse model without measurable side effects. Treatment with the full dosage of Cisplatin alone (5 mg/kg every 5 days) strongly suppressed tumor growth. However, the QOL in these mice had been significantly affected when measured by food intakes and body weight. The combinatory regiment of ACBP-L with a fewer doses of Cisplatin (5 mg/kg every 10 days) resulted in a similar anti-tumor activity with improved QOL. F-18-FDG PET/CT scan was used to examine the biological activity in tumors of live animals and indicated the consistent treatment effects. The tumor tissues were harvested after treatment, and ACBP-L and Cisplatin treatment suppressed Bcl-2, and induced Bax, Caspase 3, and Caspase 8 molecules as detected by RT-PCR and immunohistochemistry. The combinatory regiment induced stronger Bax and Caspase 8 protein expression.
Conclusion: Our current finding in this gastric cancer xenograft animal model demonstrated that ACBP-L could lower Cisplatin dose to achieve a similar anti-tumor efficacy as the higher dose of Cisplatin alone, through enhanced modulation of apoptotic molecules. This newly developed combination regiment improved QOL in tumor bearing hosts, which could lead to clinical investigation for the new strategy of combination therapy.
C1 [Su, Xiulan; Dong, Chao; Zhang, Jialing; Su, Liya; Cui, Hongwei] Inner Mongolia Med Univ, Affiliated Hosp, Clin Med Res Ctr, Hohhot 010050, Inner Mongolia, Peoples R China.
[Wang, Xuemei] Inner Mongolia Med Univ, Affiliated Hosp, PET CT Ctr, Hohhot 010050, Inner Mongolia, Peoples R China.
[Chen, Zhong] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Su, XL (reprint author), Inner Mongolia Med Univ, Affiliated Hosp, Clin Med Res Ctr, 1 Tongdao North St, Hohhot 010050, Inner Mongolia, Peoples R China.
EM xlsu@hotmail.com; chenz@nidcd.nih.gov
FU National Natural Science Foundation of China [China] [30860327]; Major
Project of the Affiliated Hospital of Inner Mongolia Medical College
[China] [ZD9809]; NIH/NIDCD [Z01-DC-000016]
FX This work was supported by the National Natural Science Foundation of
China [No. 30860327, China], Major Project of the Affiliated Hospital of
Inner Mongolia Medical College [No. ZD9809, China], and NIH/NIDCD
intramural research projects [No. Z01-DC-000016] for Zhong Chen. We
thank Dr. Ke Yang from Beijing University Medical Health Center for
helpful discussions and providing cell lines. We also thank Cindy Clark
(NIH library) for helpful editing the manuscript.
NR 35
TC 9
Z9 9
U1 2
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2045-3701
J9 CELL BIOSCI
JI Cell Biosci.
PD FEB 10
PY 2014
VL 4
AR 7
DI 10.1186/2045-3701-4-7
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AB7LO
UT WOS:000331971700001
PM 24507386
ER
PT J
AU Huang, HL
Lamikanra, AA
Alkaitis, MS
Thezenas, ML
Ramaprasad, A
Moussa, E
Roberts, DJ
Casals-Pascual, C
AF Huang, Honglei
Lamikanra, Abigail A.
Alkaitis, Matthew S.
Thezenas, Marie L.
Ramaprasad, Abhinay
Moussa, Ehab
Roberts, David J.
Casals-Pascual, Climent
TI Interleukin-10 Regulates Hepcidin in Plasmodium falciparum Malaria
SO PLOS ONE
LA English
DT Article
ID IRON; ANEMIA; INFLAMMATION; FERROPORTIN; INFECTION; IL-10; LIVER
AB Background: Acute malarial anemia remains a major public health problem. Hepcidin, the major hormone controlling the availability of iron, is raised during acute and asymptomatic parasitemia. Understanding the role and mechanism of raised hepcidin and so reduced iron availability during infection is critical to establish evidence-based guidelines for management of malaria anemia. Our recent clinical evidence suggests a potential role of IL-10 in the regulation of hepcidin in patients with acute P. falciparum malaria.
Methods: We have measured secretion of hepcidin by primary macrophages and the hepatoma cell line HepG2 stimulated with IL-10, IL-6 and Plasmodium falciparum-infected erythrocytes.
Findings: We have observed that IL-10 and IL-6 production increased in primary macrophages when these cells were cocultured with Plasmodium falciparum-infected erythrocytes. We found that IL-10 induced hepcidin secretion in primary macrophages in a dose-dependent manner but not in HepG2 cells. These effects were mediated through signal transducer and activator of transcription (STAT) 3-phosphorylation and completely abrogated by a specific STAT3 inhibitor.
Conclusion: IL-10 can directly regulate hepcidin in primary macrophages but not in HepG2 cells. This effect can be modulated by Plasmodium falciparum. The results are consistent with a role for IL-10 in modulating iron metabolism during acute phase of infection.
C1 [Huang, Honglei; Thezenas, Marie L.; Ramaprasad, Abhinay; Moussa, Ehab; Casals-Pascual, Climent] Wellcome Trust Ctr Human Genet, Oxford, England.
[Lamikanra, Abigail A.; Alkaitis, Matthew S.; Roberts, David J.] Univ Oxford, Nuffield Dept Clin Lab Sci, Oxford, England.
[Lamikanra, Abigail A.; Alkaitis, Matthew S.; Roberts, David J.] John Radcliffe Hosp, Natl Hlth Serv Blood & Transplant, Oxford OX3 9DU, England.
[Alkaitis, Matthew S.] NIAID, Lab Malaria & Vector Res, Rockville, MD USA.
[Ramaprasad, Abhinay; Moussa, Ehab] King Abdullah Univ Sci & Technol, Jeddah, Saudi Arabia.
RP Casals-Pascual, C (reprint author), Wellcome Trust Ctr Human Genet, Oxford, England.
EM ccasals@well.ox.ac.uk
RI Ramaprasad, Abhinay/D-1181-2013
OI Ramaprasad, Abhinay/0000-0001-9372-5526
FU Medical research Council [G0701885]; National Blood Service; National
Institute for Health Research; Wellcome Trust Centre for Human Genetics
(Oxford, UK) [077383/Z/05/Z]; National Health Service Blood and
Transplant - Oxford Centre
FX CC-P is supported by the Medical research Council (Clinician Scientist
Fellowship: G0701885). DJR is supported by the National Blood Service,
and the National Institute for Health Research. The research was carried
out at the Wellcome Trust Centre for Human Genetics (Oxford, UK)
[077383/Z/05/Z], and the National Health Service Blood and Transplant -
Oxford Centre. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 26
TC 6
Z9 6
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 10
PY 2014
VL 9
IS 2
AR e88408
DI 10.1371/journal.pone.0088408
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA7CL
UT WOS:000331254600075
PM 24520384
ER
PT J
AU Wang, ZL
Wang, Z
Liu, DB
Yan, XF
Wang, F
Niu, G
Yang, M
Chen, XY
AF Wang, Zhongliang
Wang, Zhe
Liu, Dingbin
Yan, Xuefeng
Wang, Fu
Niu, Gang
Yang, Min
Chen, Xiaoyuan
TI Biomimetic RNA-Silencing Nanocomplexes: Overcoming Multidrug Resistance
in Cancer Cells
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE biomimetics; drug design; gene regulation; gold; nanoparticles
ID MODIFIED GOLD NANOPARTICLES; DELIVERY; INTERFERENCE; THERAPY; SIRNA;
SIZE
AB RNA interference (RNAi) is an RNA-dependent gene silencing approach controlled by an RNA-induced silencing complex (RISC). Herein, we present a synthetic RISC-mimic nanocomplex, which can actively cleave its target RNA in a sequence-specific manner. With high enzymatic stability and efficient self-delivery to target cells, the designed nanocomplex can selectively and potently induce gene silencing without cytokine activation. These nanocomplexes, which target multidrug resistance, are not only able to bypass the P-glycoprotein (Pgp) transporter, due to their nano-size effect, but also effectively suppress Pgp expression, thus resulting in successful restoration of drug sensitivity of OVCAR8/ADR cells to Pgp-transportable cytotoxic agents. This nanocomplex approach has the potential for both functional genomics and cancer therapy.
C1 [Yang, Min] Jiangsu Inst Nucl Med, Minist Hlth, Jiangsu Key Lab Mol Nucl Med, Key Lab Nucl Med, Wuxi 214063, Peoples R China.
[Wang, Zhongliang; Wang, Zhe; Liu, Dingbin; Yan, Xuefeng; Wang, Fu; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Peoples R China.
RP Yang, M (reprint author), Jiangsu Inst Nucl Med, Minist Hlth, Jiangsu Key Lab Mol Nucl Med, Key Lab Nucl Med, Wuxi 214063, Peoples R China.
EM yangmin@jsinm.org; shawn.chen@nih.gov
RI Wang, Zhongliang/J-8674-2012;
OI Wang, Fu/0000-0001-9222-0833
FU National Natural Science Foundation [81171399, 81371596, 81101077]; CSC
Foundation [2011832173]; National Significant New Drugs Creation Program
[2012ZX09505-001-001]; National Basic Research Program of China (973
program) [2013CB733802, 2014CB744503]; Jiangsu Province Foundation
[BK2011166, BE2012622, BL2012031, BM2012066]; Outstanding Professional
Fund of Health Ministry in Jiangsu Province [RC2011095, H201028];
Intramural Research Program (IRP) of NIBIB/NIH
FX This work was supported by the National Natural Science Foundation
(81171399, 81371596 and 81101077), the CSC Foundation (2011832173), the
National Significant New Drugs Creation Program (2012ZX09505-001-001),
the National Basic Research Program of China (973 program, 2013CB733802
and 2014CB744503), the Jiangsu Province Foundation (BK2011166,
BE2012622, BL2012031, and BM2012066), the Outstanding Professional Fund
of Health Ministry in Jiangsu Province (RC2011095 and H201028), and the
Intramural Research Program (IRP) of NIBIB/NIH.
NR 35
TC 14
Z9 14
U1 8
U2 130
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1433-7851
EI 1521-3773
J9 ANGEW CHEM INT EDIT
JI Angew. Chem.-Int. Edit.
PD FEB 10
PY 2014
VL 53
IS 7
BP 1997
EP 2001
DI 10.1002/anie.201309985
PG 5
WC Chemistry, Multidisciplinary
SC Chemistry
GA 303NE
UT WOS:000330680400047
PM 24446433
ER
PT J
AU Tatem, AJ
Huang, ZJ
Narib, C
Kumar, U
Kandula, D
Pindolia, DK
Smith, DL
Cohen, JM
Graupe, B
Uusiku, P
Lourenco, C
AF Tatem, Andrew J.
Huang, Zhuojie
Narib, Clothilde
Kumar, Udayan
Kandula, Deepika
Pindolia, Deepa K.
Smith, David L.
Cohen, Justin M.
Graupe, Bonita
Uusiku, Petrina
Lourenco, Christopher
TI Integrating rapid risk mapping and mobile phone call record data for
strategic malaria elimination planning
SO MALARIA JOURNAL
LA English
DT Article
DE Human mobility; Plasmodium falciparum malaria; Malaria elimination;
Migration; Disease mapping; Spatial analysis; Satellite imagery; Mobile
phones
ID SUB-SAHARAN AFRICA; PLASMODIUM-FALCIPARUM; SPECIES DISTRIBUTIONS;
MIGRATION PATTERNS; CHILD SURVIVAL; HUMAN MOVEMENT; TRANSMISSION;
ZANZIBAR; BURDEN; KENYA
AB Background: As successful malaria control programmes re-orientate towards elimination, the identification of transmission foci, targeting of attack measures to high-risk areas and management of importation risk become high priorities. When resources are limited and transmission is varying seasonally, approaches that can rapidly prioritize areas for surveillance and control can be valuable, and the most appropriate attack measure for a particular location is likely to differ depending on whether it exports or imports malaria infections.
Methods/Results: Here, using the example of Namibia, a method for targeting of interventions using surveillance data, satellite imagery, and mobile phone call records to support elimination planning is described. One year of aggregated movement patterns for over a million people across Namibia are analyzed, and linked with case-based risk maps built on satellite imagery. By combining case-data and movement, the way human population movements connect transmission risk areas is demonstrated. Communities that were strongly connected by relatively higher levels of movement were then identified, and net export and import of travellers and infection risks by region were quantified. These maps can aid the design of targeted interventions to maximally reduce the number of cases exported to other regions while employing appropriate interventions to manage risk in places that import them.
Conclusions: The approaches presented can be rapidly updated and used to identify where active surveillance for both local and imported cases should be increased, which regions would benefit from coordinating efforts, and how spatially progressive elimination plans can be designed. With improvements in surveillance systems linked to improved diagnosis of malaria, detailed satellite imagery being readily available and mobile phone usage data continually being collected by network providers, the potential exists to make operational use of such valuable, complimentary and contemporary datasets on an ongoing basis in infectious disease control and elimination.
C1 [Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Tatem, Andrew J.; Smith, David L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Huang, Zhuojie; Pindolia, Deepa K.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Huang, Zhuojie; Kumar, Udayan; Pindolia, Deepa K.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA.
[Narib, Clothilde; Uusiku, Petrina; Lourenco, Christopher] Natl Vector Borne Dis Control Programme, Windhoek, Namibia.
[Kumar, Udayan] Univ Florida, Dept Comp Sci, Gainesville, FL USA.
[Kandula, Deepika; Cohen, Justin M.; Lourenco, Christopher] Clinton Hlth Access Initiat, Boston, MA USA.
[Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Graupe, Bonita] Mobile Telecommun Ltd, Windhoek, Namibia.
RP Tatem, AJ (reprint author), Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
EM A.J.Tatem@soton.ac.uk
RI Emchi, Karma/Q-1952-2016; Smith, David/L-8850-2013;
OI Smith, David/0000-0003-4367-3849; Cohen, Justin/0000-0003-4481-6784
FU RAPIDD program of the Science and Technology Directorate, Department of
Homeland Security; Fogarty International Center, National Institutes of
Health; NIH/NIAID [U19AI089674]; Bill and Melinda Gates Foundation
[49446, 1032350]
FX The work was undertaken under a data sharing agreement between MTC
Namibia, the Namibian National Vector-borne Diseases Control Programme
and the Clinton Health Access Initiative. The authors are grateful to
MTC for sharing their data and help with extractions. This work
represents part of the Human Mobility Mapping Project
(http://www.thummp.org), Flowminder (www.flowminder.org) and the
WorldPop population mapping project (http://www.worldpop.org.uk). AJT &
DLS acknowledge 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 are
also supported by grants from NIH/NIAID (U19AI089674) and 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 64
TC 36
Z9 37
U1 8
U2 36
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 10
PY 2014
VL 13
AR 52
DI 10.1186/1475-2875-13-52
PG 15
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA AA9IN
UT WOS:000331407100001
PM 24512144
ER
PT J
AU Blydt-Hansen, TD
Pierce, CB
Cai, Y
Samsonov, D
Massengill, S
Moxey-Mims, M
Warady, BA
Furth, SL
AF Blydt-Hansen, Tom D.
Pierce, Christopher B.
Cai, Yi
Samsonov, Dmitri
Massengill, Susan
Moxey-Mims, Marva
Warady, Bradley A.
Furth, Susan L.
TI Medication Treatment Complexity and Adherence in Children with CKD
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; RENAL TUBULAR-ACIDOSIS;
GLOMERULAR-FILTRATION-RATE; PILL BURDEN; ANTIRETROVIRAL THERAPY;
OBSTRUCTIVE UROPATHY; PATHOGENESIS; TRANSPLANTATION; NONADHERENCE;
PROGRESSION
AB Background and objectives The complexity of CKD management in children is increased by the number of comorbid conditions. This study assessed the prevalence of comorbidities in pediatric CKD and the frequency with which multiple comorbidities present together by assessing prevalent medication use by CKD stage and diagnosis and their association with clinical or sociodemographic factors. The association between number and frequency of dosing of medications prescribed and self-report of nonadherence was also assessed.
Design, setting, participants, & measurements In this cross-sectional analysis of the Chronic Kidney Disease in Children study, medication use at study entry grouped by indication was examined by CKD stage, diagnosis, age, race, ethnicity, income, and CKD duration. Multivariate adjusted predictors of medication use and clustering were examined. Nonadherence was assessed by self-report of missed medications in the past 7 days.
Results The 558 eligible participants had a median age of 11 years and median GFR of 44 ml/min per 1.73 m(2); 62% of participants were male and 78% had nonglomerular kidney disease. The number of medications for treatment of CKD comorbidities increased with advanced CKD stage (2.5-fold for stages IV versus II; P<0.001) and glomerular disease (1.4-fold versus nonglomerular; P<0.001). Three distinct medication clusters were identified that corresponded to treatment of glomerular disease, advanced renal tubular dysfunction, and proteinuric complications, respectively. Nonadherence was associated with increased medication dosing frequency (administration>2 times/d; P<0.001) but not the number of medications.
Conclusions Medical therapy for children with CKD is complex and is affected by glomerular diagnosis, CKD stage, and medication frequency. The need for CKD-related medication treatment cannot be easily predicted by CKD staging alone. Poorer adherence was associated with increased medication frequency, but not with the number of medical problems needing treatment. Consolidating medical treatment and reducing medication frequency may improve adherence rates in children with CKD.
C1 [Blydt-Hansen, Tom D.] Univ Manitoba, Dept Pediat & Child Hlth, Childrens Hosp, Hlth Sci Ctr,Div Pediat Nephrol, Winnipeg, MB R3A 1S1, Canada.
[Moxey-Mims, Marva] NIDDK, Bethesda, MD 20892 USA.
RP Blydt-Hansen, TD (reprint author), Univ Manitoba, Dept Pediat & Child Hlth, Childrens Hosp, Hlth Sci Ctr,Div Pediat Nephrol, FE009 840 Sherbrook St, Winnipeg, MB R3A 1S1, Canada.
EM tblydthansen@hsc.mb.ca
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institute of Neurological Disorders and Stroke; National
Institute of Child Health and Human Development; National Heart, Lung,
and Blood Institute
FX The CKiD study is supported by grants from the National Institute of
Diabetes and Digestive and Kidney Diseases, the National Institute of
Neurological Disorders and Stroke, the National Institute of Child
Health and Human Development, and the National Heart, Lung, and Blood
Institute. The study sponsors had a role in the study design, analysis,
interpretation of data, writing this manuscript, and the decision to
submit the manuscript for publication.
NR 27
TC 4
Z9 4
U1 1
U2 3
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
EI 1555-905X
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD FEB 7
PY 2014
VL 9
IS 2
BP 247
EP 254
DI 10.2215/CJN.05750513
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA AI9FY
UT WOS:000337238400007
PM 24262500
ER
PT J
AU Quail, MA
Smith, M
Jackson, D
Leonard, S
Skelly, T
Swerdlow, HP
Gu, Y
Ellis, P
AF Quail, Michael A.
Smith, Miriam
Jackson, David
Leonard, Steven
Skelly, Thomas
Swerdlow, Harold P.
Gu, Yong
Ellis, Peter
TI SASI-Seq: sample assurance Spike-Ins, and highly differentiating 384
barcoding for Illumina sequencing
SO BMC GENOMICS
LA English
DT Article
DE Next-generation sequencing; Indexing; Barcode; Illumina; Sample
assurance; Spike-in; Contamination; Sample identity
ID GENOME; CONTAMINATION; ERROR; DNA; MUTATIONS; LIBRARIES; GENOTYPE
AB Background: A minor but significant fraction of samples subjected to next-generation sequencing methods are either mixed-up or cross-contaminated. These events can lead to false or inconclusive results. We have therefore developed SASI-Seq; a process whereby a set of uniquely barcoded DNA fragments are added to samples destined for sequencing. From the final sequencing data, one can verify that all the reads derive from the original sample(s) and not from contaminants or other samples.
Results: By adding a mixture of three uniquely barcoded amplicons, of different sizes spanning the range of insert sizes one would normally use for Illumina sequencing, at a spike-in level of approximately 0.1%, we demonstrate that these fragments remain intimately associated with the sample. They can be detected following even the tightest size selection regimes or exome enrichment and can report the occurrence of sample mix-ups and cross-contamination.
As a consequence of this work, we have designed a set of 384 eleven-base Illumina barcode sequences that are at least 5 changes apart from each other, allowing for single-error correction and very low levels of barcode misallocation due to sequencing error.
Conclusion: SASI-Seq is a simple, inexpensive and flexible tool that enables sample assurance, allows deconvolution of sample mix-ups and reports levels of cross-contamination between samples throughout NGS workflows.
C1 [Quail, Michael A.; Smith, Miriam; Jackson, David; Leonard, Steven; Swerdlow, Harold P.; Gu, Yong; Ellis, Peter] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England.
[Skelly, Thomas] Frederick Natl Lab Canc Res, Leidos Biomed Res, Frederick, MD 21702 USA.
RP Quail, MA (reprint author), Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England.
EM mq1@sanger.ac.uk
FU Wellcome Trust [098051]; European Union [262055]
FX The authors thank the Wellcome Trust Sanger Institute core sequencing
and informatics teams. This work was supported by the Wellcome Trust
[grant number 098051] and from the European Union Seventh Framework
Programme (FP7/2007-2013) under grant agreement no. 262055. We also
thank Simon Harris of the Wellcome Trust Sanger Institute who analysed
sequence data for false variant calls.
NR 37
TC 11
Z9 11
U1 4
U2 19
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 7
PY 2014
VL 15
AR 110
DI 10.1186/1471-2164-15-110
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AD8NU
UT WOS:000333523700001
PM 24507442
ER
PT J
AU Koh, KH
Pan, X
Shen, HW
Arnold, SLM
Yu, AM
Gonzalez, FJ
Isoherranen, N
Jeong, H
AF Koh, Kwi Hye
Pan, Xian
Shen, Hong-Wu
Arnold, Samuel L. M.
Yu, Ai-Ming
Gonzalez, Frank J.
Isoherranen, Nina
Jeong, Hyunyoung
TI Altered Expression of Small Heterodimer Partner Governs Cytochrome P450
(CYP) 2D6 Induction during Pregnancy in CYP2D6-humanized Mice
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Cytochrome P450; Drug Metabolism; Pregnancy; Retinoid; Transgenic Mice;
HNF4; SHP
ID NUCLEAR FACTOR 4-ALPHA; BILE-ACID CONCENTRATIONS; GENE-EXPRESSION;
MOLECULAR-BASIS; X-RECEPTOR; TRANSCRIPTIONAL REGULATION; LIPID
HOMEOSTASIS; DRUG-METABOLISM; HUMANIZED MOUSE;
HEPATOCYTE-NUCLEAR-FACTOR-4-ALPHA
AB Background: CYP2D6-mediated drug metabolism is enhanced during pregnancy, but the underlying mechanisms remain unknown. Results: In CYP2D6-humanized mice, CYP2D6 induction during pregnancy was linked to decreased expression of SHP, a repressor of CYP2D6 expression. Conclusion: Decreased SHP expression may account for CYP2D6 induction during pregnancy. Significance: This may provide a mechanistic basis in designing optimal dosage regimens in pregnant women.
Substrates of a major drug-metabolizing enzyme CYP2D6 display increased elimination during pregnancy, but the underlying mechanisms are unknown in part due to a lack of experimental models. Here, we introduce CYP2D6-humanized (Tg-CYP2D6) mice as an animal model where hepatic CYP2D6 expression is increased during pregnancy. In the mouse livers, expression of a known positive regulator of CYP2D6, hepatocyte nuclear factor 4 (HNF4), did not change during pregnancy. However, HNF4 recruitment to CYP2D6 promoter increased at term pregnancy, accompanied by repressed expression of small heterodimer partner (SHP). In HepG2 cells, SHP repressed HNF4 transactivation of CYP2D6 promoter. In transgenic (Tg)-CYP2D6 mice, SHP knockdown led to a significant increase in CYP2D6 expression. Retinoic acid, an endogenous compound that induces SHP, exhibited decreased hepatic levels during pregnancy in Tg-CYP2D6 mice. Administration of all-trans-retinoic acid led to a significant decrease in the expression and activity of hepatic CYP2D6 in Tg-CYP2D6 mice. This study provides key insights into mechanisms underlying altered CYP2D6-mediated drug metabolism during pregnancy, laying a foundation for improved drug therapy in pregnant women.
C1 [Koh, Kwi Hye; Jeong, Hyunyoung] Univ Illinois, Coll Pharm, Dept Pharm Practice, Chicago, IL 60612 USA.
[Pan, Xian; Jeong, Hyunyoung] Univ Illinois, Coll Pharm, Dept Biopharmaceut Sci, Chicago, IL 60612 USA.
[Shen, Hong-Wu; Yu, Ai-Ming] Univ Calif Davis, Med Ctr, Dept Biochem & Mol Med, Sacramento, CA 95817 USA.
[Arnold, Samuel L. M.; Isoherranen, Nina] Univ Washington, Sch Pharm, Dept Pharmaceut, Seattle, WA 98195 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Jeong, H (reprint author), Univ Illinois, Dept Pharm Practice MC 886, 833 S Wood St, Chicago, IL 60612 USA.
EM yjeong@uic.edu
FU National Institutes of Health [HD065532, K12HK055892]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant HD065532 and Fellowship K12HK055892 (NICHD; to H. J.).
NR 51
TC 16
Z9 16
U1 1
U2 22
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 7
PY 2014
VL 289
IS 6
BP 3105
EP 3113
DI 10.1074/jbc.M113.526798
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AA8TU
UT WOS:000331368700001
PM 24318876
ER
PT J
AU Spruiell, K
Richardson, RM
Cullen, JM
Awumey, EM
Gonzalez, FJ
Gyamfi, MA
AF Spruiell, Krisstonia
Richardson, Ricardo M.
Cullen, John M.
Awumey, Emmanuel M.
Gonzalez, Frank J.
Gyamfi, Maxwell A.
TI Role of Pregnane X Receptor in Obesity and Glucose Homeostasis in Male
Mice
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Diabetes; Metabolic Syndrome; Nuclear Receptors; Obesity; Peroxisome
Proliferator-activated Receptor (PPAR)
ID ACTIVATED PROTEIN-KINASE; HIGH-FAT DIET; CONSTITUTIVE ANDROSTANE
RECEPTOR; LOW PLASMA LEPTIN; NUCLEAR RECEPTOR; CROSS-TALK;
INSULIN-RESISTANCE; INDUCED THERMOGENESIS; TARGETED DISRUPTION; HEPATIC
STEATOSIS
AB Background: PXR is a xenobiotic nuclear receptor that defends against toxic agents. Results: In male mice fed a HFD, the mouse PXR gene promoted obesity, whereas mice lacking the PXR or possessing the human transgene were hyperglycemic. Conclusion: The impact of PXR on HFD-induced obesity and hyperglycemia is species-dependent. Significance: The current data provide in vivo significance of PXR in metabolic syndrome.
Clinical obesity is a complex metabolic disorder affecting one in three adults. Recent reports suggest that pregnane X receptor (PXR), a xenobiotic nuclear receptor important for defense against toxic agents and for eliminating drugs and other xenobiotics, may be involved in obesity. Noting differences in ligand specificities between human and mouse PXRs, the role of PXR in high fat diet (HFD)-induced obesity was examined using male PXR-humanized (hPXR) transgenic and PXR-knock-out (PXR-KO) mice in comparison to wild-type (WT) mice. After 16 weeks on either a control diet or HFD, WT mice showed greater weight gain, whereas PXR-KO mice gained less weight due to their resistance to HFD-induced decreases in adipose tissue peroxisome proliferator-activated receptor and induction of hepatic carnitine palmitoyltransferase 1, suggesting increased energy metabolism. Interestingly, control-fed PXR-KO mice exhibited hepatomegaly, hyperinsulinemia, and hyperleptinemia but hypoadiponectinemia and lower adiponectin receptor R2 mRNA levels relative to WT mice. Evaluation of these biologic indicators in hPXR mice fed a control diet or HFD revealed further differences between the mouse and human receptors. Importantly, although HFD-fed hPXR mice were resistant to HFD-induced obesity, both PXR-KO and hPXR mice exhibited impaired induction of glucokinase involved in glucose utilization and displayed elevated fasting glucose levels and severely impaired glucose tolerance. Moreover, the basal hepatic levels of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase 1 were increased in hPXR mice compared with WT mice. Altogether, although the mouse PXR promotes HFD-induced obesity, the hPXR mouse carries a genetic predisposition for type 2 diabetes and thus provides a model for exploring the role of human PXR in the metabolic syndrome.
C1 [Spruiell, Krisstonia; Richardson, Ricardo M.; Awumey, Emmanuel M.; Gyamfi, Maxwell A.] N Carolina Cent Univ, Julius L Chambers Biomed Biotechnol Res Inst, Durham, NC 27707 USA.
[Cullen, John M.] N Carolina State Univ, North Carolina Coll Vet Med, Raleigh, NC 27607 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Gyamfi, MA (reprint author), N Carolina Cent Univ, JLC Biomed Biotechnol Res Inst, Cardiovasc & Metab Dis Res Program, 700 George St, Durham, NC 27707 USA.
EM mgyamfi@nccu.edu
FU National Institutes of Health [U54 AA019765, SC1 HL099139, U54 CA156735,
RO1 HL064761, R25HL059868, P20 MD000175]; National Cancer Institute
Intramural Research Program
FX This work was supported, in whole or in part, by National Institutes of
Health Grants U54 AA019765, SC1 HL099139, U54 CA156735, RO1 HL064761,
R25HL059868, and P20 MD000175, and the National Cancer Institute
Intramural Research Program.
NR 71
TC 16
Z9 18
U1 5
U2 10
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 7
PY 2014
VL 289
IS 6
BP 3244
EP 3261
DI 10.1074/jbc.M113.494575
PG 18
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AA8TU
UT WOS:000331368700013
PM 24362030
ER
PT J
AU Lee, JG
Kim, W
Gygi, S
Ye, YH
AF Lee, Jin-Gu
Kim, Woong
Gygi, Steven
Ye, Yihong
TI Characterization of the Deubiquitinating Activity of USP19 and Its Role
in Endoplasmic Reticulum-associated Degradation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Deubiquitination; ER-associated Degradation; Hsp90; Membrane Proteins;
Ubiquitin; USP19; Tail-anchored Protein Biogenesis
ID UBIQUITIN LIGASE; CHAINS; MECHANISMS; INSERTION; PROTEINS; ENZYMES; ER
AB Background: The regulation and function of USP19 is unknown. Results: We identify Hsp90 as a USP19 interactor and regulator. USP19 is predominantly localized in the cytosol despite having a transmembrane domain. Conclusion: USP19 is a Hsp90-regulated deubiquitinase dispensable for ERAD. Significance: The study reveals a novel means of DUB regulation involving chaperone association and membrane integration.
Deubiquitinating enzymes (DUBs) regulate various cellular processes ranging from protein degradation to cellular signaling. USP19, the only DUB containing a carboxyl-terminal transmembrane domain, was proposed to function in endoplasmic reticulum-associated degradation (ERAD). Here we characterize the function and regulation of USP19. We identify Hsp90 as a specific partner that binds the catalytic domain of USP19 to promote substrate association. Intriguingly, although overexpressed USP19 interacts with Derlin-1 and other ERAD machinery factors in the membrane, endogenous USP19 is mostly in the cytosol where it binds Hsp90. Accordingly, we detect neither interaction of endogenous USP19 with Derlin-1 nor significant effect on ERAD by USP19 depletion. The USP19 transmembrane domain appears to be partially stabilized in the cytosol by an interaction with its own catalytic domain, resulting in auto-inhibition of its deubiquitinating activity. These results clarify the role of USP19 in ERAD and suggest a novel DUB regulation that involves chaperone association and membrane integration. Moreover, our study indicates that the localization of tail-anchored membrane proteins can be subject to regulation in cells.
C1 [Lee, Jin-Gu; Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Kim, Woong; Gygi, Steven] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
RP Ye, YH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM yihongy@mail.nih.gov
FU NIDDK of the National Institutes of Health
FX This research was supported by the Intramural Research Program of the
NIDDK of the National Institutes of Health.
NR 20
TC 11
Z9 11
U1 1
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 7
PY 2014
VL 289
IS 6
BP 3510
EP 3517
DI 10.1074/jbc.M113.538934
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AA8TU
UT WOS:000331368700035
PM 24356957
ER
PT J
AU Khalaj, M
Abbasi, A
Yamanishi, H
Akiyama, K
Wakitani, S
Kikuchi, S
Hirose, M
Yuzuriha, M
Magari, M
Degheidy, HA
Abe, K
Ogura, A
Hashimoto, H
Kunieda, T
AF Khalaj, Maryam
Abbasi, Abdolrahim
Yamanishi, Hiroshi
Akiyama, Kouyou
Wakitani, Shuso
Kikuchi, Sotaro
Hirose, Michiko
Yuzuriha, Misako
Magari, Masaki
Degheidy, Heba A.
Abe, Kuniya
Ogura, Atsuo
Hashimoto, Hiroshi
Kunieda, Tetsuo
TI A Missense Mutation in Rev7 Disrupts Formation of Pol zeta, Impairing
Mouse Development and Repair of Genotoxic Agent-induced DNA Lesions
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Cell Proliferation; DNA Polymerase; Embryo; Mouse Genetics; Mutant
ID PRIMORDIAL GERM-CELLS; CROSS-LINK REPAIR; POLYMERASE-ZETA;
FANCONI-ANEMIA; EMBRYONIC LETHALITY; CHROMOSOMAL INSTABILITY; GENOMIC
INSTABILITY; CATALYTIC SUBUNIT; MAMMALIAN-CELLS; B-CELLS
AB Background:Rev7 encodes a subunit of Pol for translesion DNA synthesis (TLS). Results: We found a Rev7 mutation in mice that causes developmental defects and increases susceptibility for genotoxicity. Conclusion:Rev7 is essential for mouse development through its function in cell proliferation. Significance: These findings demonstrate a unique function of Pol in development that is absent in other TLS polymerases. Repro22 is a mutant mouse produced via N-ethyl-N-nitrosourea-induced mutagenesis that shows sterility with germ cell depletion caused by defective proliferation of primordial germ cells, decreased body weight, and partial lethality during embryonic development. Using a positional cloning strategy, we identified a missense mutation in Rev7/Mad2l2 (Rev7(C70R)) and confirmed that the mutation is the cause of the defects in repro22 mice through transgenic rescue with normal Rev7. Rev7/Mad2l2 encodes a subunit of DNA polymerase (Pol), 1 of 10 translesion DNA synthesis polymerases known in mammals. The mutant REV7 did not interact with REV3, the catalytic subunit of Pol. Rev7(C70R/C70R) cells showed decreased proliferation, increased apoptosis, and arrest in S phase with extensive H2AX foci in nuclei that indicated accumulation of DNA damage after treatment with the genotoxic agent mitomycin C. The Rev7(C70R) mutation does not affect the mitotic spindle assembly checkpoint. These results demonstrated that Rev7 is essential in resolving the replication stalls caused by DNA damage during S phase. We concluded that Rev7 is required for primordial germ cell proliferation and embryonic viability and development through the translesion DNA synthesis activity of Pol preserving DNA integrity during cell proliferation, which is required in highly proliferating embryonic cells.
C1 [Khalaj, Maryam; Abbasi, Abdolrahim; Yamanishi, Hiroshi; Wakitani, Shuso; Magari, Masaki] Okayama Univ, Grad Sch Nat Sci & Technol, Okayama 7008530, Japan.
[Akiyama, Kouyou; Kunieda, Tetsuo] Okayama Univ, Grad Sch Environm & Life Sci, Okayama 7008530, Japan.
[Khalaj, Maryam; Abbasi, Abdolrahim] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Kikuchi, Sotaro; Hashimoto, Hiroshi] Yokohama City Univ, Grad Sch Nanobiosci, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
[Hirose, Michiko; Yuzuriha, Misako; Abe, Kuniya; Ogura, Atsuo] RIKEN Bioresource Ctr, Tsukuba, Ibaraki 3050074, Japan.
[Degheidy, Heba A.] US FDA, Div Biol, Silver Spring, MD 20993 USA.
RP Abbasi, A (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM abbasiar@mail.nih.gov; tkunieda@cc.okayama-u.ac.jp
RI Ogura, Atsuo/J-3916-2014
OI Ogura, Atsuo/0000-0003-0447-1988
FU Japan Society for the Promotion of Science
FX This work was authored, in whole or in part, by National Institutes of
Health staff. This work was supported in part by grants from the Japan
Society for the Promotion of Science.
NR 60
TC 10
Z9 10
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 7
PY 2014
VL 289
IS 6
BP 3811
EP 3824
DI 10.1074/jbc.M113.514752
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AA8TU
UT WOS:000331368700060
PM 24356953
ER
PT J
AU Teng, CT
Beames, B
Merrick, BA
Martin, N
Romeo, C
Jetten, AM
AF Teng, Christina T.
Beames, Burton
Merrick, B. Alex
Martin, Negin
Romeo, Charles
Jetten, Anton M.
TI Development of a stable cell line with an intact PGC-1 alpha/ERR alpha
axis for screening environmental chemicals
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE PGC-1 alpha/ERR alpha; Stable cell line; XCT790; Luc reporter; Screen;
EDC
ID ESTROGEN-RELATED RECEPTOR; ERR-ALPHA; GENE-EXPRESSION; TRANSCRIPTIONAL
CONTROL; ENERGY-EXPENDITURE; NUCLEAR RECEPTORS; INVERSE AGONIST;
PGC-1-ALPHA; ORPHAN; COACTIVATOR
AB The estrogen-related receptor alpha (ERR alpha) and the peroxisome proliferator-activated receptor gamma (PPAR gamma) coactivator 1 alpha (PGC-1 alpha) play critical roles in the control of several physiological functions, including the regulation of genes involved in energy homeostasis. However, little is known about the ability of environmental chemicals to disrupt or modulate this important bioenergetics pathway in humans. The goal of this study was to develop a cell-based assay system with an intact PGC-1 alpha/ERR alpha axis that could be used as a screening assay for detecting such chemicals. To this end, we successfully generated several stable cell lines expressing PGC-1 alpha and showed that the reporter driven by the native ERRa hormone response unit (AAB-Luc) is active in these cell lines and that the activation is PGC-1 alpha-dependent. Furthermore, we show that this activation can be blocked by the ERR alpha selective inverse agonist, XCT790. In addition, we find that genistein and bisphenol A further stimulate the reporter activity, while kaempferol has minimal effect. These cell lines will be useful for identifying environmental chemicals that modulate this important pathway. Published by Elsevier Inc.
C1 [Teng, Christina T.; Beames, Burton; Merrick, B. Alex] NIEHS, DNTP, Biomol Screening Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Martin, Negin; Romeo, Charles] NIEHS, DIR, Viral Core Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Jetten, Anton M.] NIEHS, DIR, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
RP Teng, CT (reprint author), NIEHS, DNTP, BSB, POB 12233,MD K2-17,111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM teng1@niehs.nih.gov
OI Jetten, Anton/0000-0003-0954-4445
FU Intramural Research Programs; Division of National Toxicology Program
(DNTP); Division of Intramural Research (DIR); National Institute of
Environmental Health Sciences, National Institutes of Health (NIH)
FX We thank members of Dr. Anton Jetten's laboratory for technical advice
and support. We appreciate comments on the manuscript by Drs. H.
Kinyamu, S. Ferguson, and R. Tice. This research was supported by the
Intramural Research Programs, Division of National Toxicology Program
(DNTP) and Division of Intramural Research (DIR), the National Institute
of Environmental Health Sciences, National Institutes of Health (NIH).
NR 38
TC 2
Z9 3
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD FEB 7
PY 2014
VL 444
IS 2
BP 177
EP 181
DI 10.1016/j.bbrc.2014.01.033
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA AB6TX
UT WOS:000331923500012
PM 24457025
ER
PT J
AU Thomas, MA
Demberg, T
Vargas-Inchaustegui, DA
Xiao, P
Tuero, I
Venzon, D
Weiss, D
Treece, J
Robert-Guroff, M
AF Thomas, Michael A.
Demberg, Thorsten
Vargas-Inchaustegui, Diego A.
Xiao, Peng
Tuero, Iskra
Venzon, David
Weiss, Deborah
Treece, James
Robert-Guroff, Marjorie
TI Rhesus macaque rectal and duodenal tissues exhibit B-cell
sub-populations distinct from peripheral blood that continuously secrete
antigen-specific IgA in short-term explant cultures
SO VACCINE
LA English
DT Article
DE SIV/SHIV infected rhesus macaques; Mucosal explant cultures; Memory
B-cells; IgA; AIDS vaccine
ID IMMUNODEFICIENCY VIRUS-INFECTION; PLASMA-CELLS; GASTROINTESTINAL-TRACT;
NONHUMAN-PRIMATES; IMMUNE-RESPONSES; IN-VITRO; MUCOSAL; SIV; HIV;
VACCINE
AB It is becoming increasingly obvious that evaluation of a vaccine aimed at preventing HIV infection should include assessment of induced immunity at mucosal sites of viral entry. Among the most salient immune responses are viral-specific antibodies. A recent report on IgA-secreting plasma cells in human duodenal explants prompted us to examine similar duodenal and rectal biopsies of rhesus macaques, a key animal model for pre-clinical HIV/SIV vaccine studies, and characterize the local resident B-cells. Here we report that non-human primate rectal explants possess similar levels of B-cells as duodenal explants. We characterize the antibody isotype expression on mucosal memory B-cells and show for the first time that the B-cell memory subsets of the duodenum and rectum are distinct from those of PBMC, not only by essentially lacking CD27(+) cells, as previously reported for uninfected macaques (Titanji et al., 2010), but also in being mostly IgD(-). SIV- and SHIV-infected macaques had fewer total IgA-secreting cells in rectal tissue compared to naive macaques. As expected, the fractions of B-cells with surface expression of IgA were dominant in the rectal and duodenal explants whereas in PBMC IgG surface expression was dominant among IgD- B-cells. Mucosal antibody secreting cells were found to be predominantly plasma cells/plasma blasts based on their lack of response to stimulation. Importantly, short-term culture of rectal explants of SIV- and SHIV-positive animals led to secretion of Env-specific IgA into the culture supernatant which could be easily measured by ELISA. Collection of such culture supernatant over several days allows for accumulation of mucosal antibody in amounts that should enable antibody purification, characterization, and use in functional assays. Rectal explants can be readily obtained and unequivocally identify the mucosal tissue as the source of antibody. Overall they facilitate evaluation of mucosal vaccines. Published by Elsevier Ltd.
C1 [Thomas, Michael A.; Demberg, Thorsten; Vargas-Inchaustegui, Diego A.; Xiao, Peng; Tuero, Iskra; Robert-Guroff, Marjorie] NCI, Sect Immune Biol Retroviral Infect, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
[Weiss, Deborah; Treece, James] Adv BioSci Labs Inc, Rockville, MD USA.
RP Robert-Guroff, M (reprint author), Bldg 41,Room D804, Bethesda, MD 20892 USA.
EM guroffm@mail.nih.gov
FU Intramural NIH HHS [ZIA BC011058-02]
NR 42
TC 8
Z9 8
U1 1
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD FEB 7
PY 2014
VL 32
IS 7
BP 872
EP 880
DI 10.1016/j.vaccine.2013.12.014
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AB0SI
UT WOS:000331502000018
PM 24374153
ER
PT J
AU Langel, FD
Chiang, CY
Lane, D
Kenny, T
Ojeda, JF
Zhong, Y
Che, JW
Zhou, YY
Ribot, W
Kota, KP
Bavari, S
Panchal, RG
AF Langel, Felicia D.
Chiang, Chih-Yuan
Lane, Douglas
Kenny, Tara
Ojeda, Jenifer F.
Zhong, Yang
Che, Jianwei
Zhou, Yingyao
Ribot, Wilson
Kota, Krishna P.
Bavari, Sina
Panchal, Rekha G.
TI Alveolar Macrophages Infected with Ames or Sterne Strain of Bacillus
anthracis Elicit Differential Molecular Expression Patterns
SO PLOS ONE
LA English
DT Article
ID NF-KAPPA-B; LETHAL FACTOR; REGULATORY FACTOR-3; GENE-EXPRESSION;
KINASE-KINASE; TNF-ALPHA; IN-VIVO; ACTIVATION; INFLAMMATION; APOPTOSIS
AB Alveolar macrophages (AMs) phagocytose Bacillus anthracis following inhalation and induce the production of proinflammatory cytokines and chemokines to mediate the activation of innate immunity. Ames, the virulent strain of B. anthracis, contains two plasmids that encode the antiphagocytic poly-gamma-d-glutamic acid capsule and the lethal toxin. The attenuated Sterne strain of B. anthracis, which lacks the plasmid encoding capsule, is widely adapted as a vaccine strain. Although differences in the outcome of infection with the two strains may have originated from the presence or absence of an anti-phagocytic capsule, the disease pathogenesis following infection will be manifested via the host responses, which is not well understood. To gain understanding of the host responses at cellular level, a microarray analysis was performed using primary rhesus macaque AMs infected with either Ames or Sterne spores. Notably, 528 human orthologs were identified to be differentially expressed in AMs infected with either strain of the B. anthracis. Meta-analyses revealed genes differentially expressed in response to B. anthracis infection were also induced upon infections with multiple pathogens such as Francisella Novicida or Staphylococcus aureus. This suggests the existence of a common molecular signature in response to pathogen infections. Importantly, the microarray and protein expression data for certain cytokines, chemokines and host factors provide further insights on how cellular processes such as innate immune sensing pathways, anti-apoptosis versus apoptosis may be differentially modulated in response to the virulent or vaccine strain of B. anthracis. The reported differences may account for the marked difference in pathogenicity between these two strains.
C1 [Langel, Felicia D.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Chiang, Chih-Yuan; Ojeda, Jenifer F.; Bavari, Sina; Panchal, Rekha G.] US Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USA.
[Lane, Douglas; Kenny, Tara] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Zhong, Yang; Che, Jianwei; Zhou, Yingyao] Novartis Res Fdn, Genom Inst, San Diego, CA USA.
[Ribot, Wilson] US Army Med Res Inst Infect Dis, Bacteriol Div, Ft Detrick, MD USA.
[Kota, Krishna P.] Perkin Elmer, Waltham, MA USA.
RP Panchal, RG (reprint author), US Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Ft Detrick, MD 21702 USA.
EM rekha.g.panchal.civ@mail.mil
FU Department of Defense Chemical Biological Defense Program through the
Defense Threat Reduction Agency (DTRA) [JSTO-CBD 2.10019_09_RD_B];
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This work was funded by the Department of Defense Chemical Biological
Defense Program through the Defense Threat Reduction Agency (DTRA)
JSTO-CBD 2.10019_09_RD_B (to R.G.P). 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
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 34
TC 0
Z9 0
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 7
PY 2014
VL 9
IS 2
AR e87201
DI 10.1371/journal.pone.0087201
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA1CR
UT WOS:000330834400011
PM 24516547
ER
PT J
AU Powers, JF
Korgaonkar, PG
Fliedner, S
Giubellino, A
Pacak, K
Sahagian, GG
Tischler, AS
AF Powers, James F.
Korgaonkar, Parimal G.
Fliedner, Stephanie
Giubellino, Alessio
Pacak, Karel
Sahagian, G. Gary
Tischler, Arthur S.
TI Cytocidal Activities of Topoisomerase 1 Inhibitors and 5-Azacytidine
against Pheochromocytoma/Paraganglioma Cells in Primary Human Tumor
Cultures and Mouse Cell Lines
SO PLOS ONE
LA English
DT Article
ID GENE-EXPRESSION; DNA METHYLATION; IN-VIVO; CAMPTOTHECIN; PROMOTER;
NANOPARTICLES; PARAGANGLIOMA; APOPTOSIS; THERAPY; CANCER
AB There is currently no effective treatment for metastatic pheochromocytomas and paragangliomas. A deficiency in current chemotherapy regimens is that the metastases usually grow very slowly. Drugs that target dividing tumor cells have therefore had limited success. To improve treatment, new strategies and valid experimental models are required for preclinical testing. However, development of models has itself been hampered by the absence of human pheochromocytoma/paraganglioma cell lines for cultures or xenografts. Topoisomerase 1 (TOP1) inhibitors are drugs that interfere with mechanisms that maintain DNA integrity during transcription in both quiescent and dividing cells. We used primary cultures of representative human tumors to establish the cytotoxicity of camptothecin, a prototypical TOP1 inhibitor, against nondividing pheochromocytoma/paraganglioma cells, and then employed a mouse pheochromocytoma model (MPC) to show that efficacy of low concentrations of camptothecin and other TOP1 inhibitors is increased by intermittent coadministration of sub-toxic concentrations of 5-azacytidine, a DNA methylation inhibitor that modulates transcription. We then tested the same drugs against a clonal MPC derivative that expresses CMV reporter-driven luciferase and GFP, intended for in vivo drug testing. Unexpectedly, luciferase expression, bioluminescence and GFP expression were paradoxically increased by both camptothecin and SN38, the active metabolite of irinotecan, thereby masking cell death. Expression of chromogranin A, a marker for neuroendocrine secretory granules, was not increased, indicating that the drug effects on levels of luciferase and GFP are specific to the GFP-luciferase construct rather than generalized cellular responses. Our findings provide proof of principle for use of TOP1 inhibitors against pheochromocytoma/paraganglioma and suggest novel strategies for enhancing efficacy and reducing toxicity by optimizing the combination and timing of their use in conjunction with other drugs. The paradoxical effects of TOP1 inhibitors on luciferase and GFP dictate a need for caution in the use of CMV promoter-regulated constructs for cancer-related imaging studies.
C1 [Powers, James F.; Tischler, Arthur S.] Tufts Med Ctr, Dept Pathol, Boston, MA 02111 USA.
[Korgaonkar, Parimal G.] Tufts Univ, Sch Med, Small Anim Imaging Preclin Testing Facil, Boston, MA 02111 USA.
[Fliedner, Stephanie; Giubellino, Alessio] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Fliedner, Stephanie] Univ Med Ctr Schleswig Holstein Lubeck, Dept Med 1, Lubeck, Germany.
RP Powers, JF (reprint author), Tufts Med Ctr, Dept Pathol, Boston, MA 02111 USA.
EM jpowers1@tuftsmedicalcenter.org
FU Department of Defense [PR100171]; Pheo Para Alliance
FX JF Powers and AS Tischler were supported by grant PR100171 from the
Department of Defense and by a grant from the Pheo Para Alliance
(http://www.pheo-para-alliance.org/). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 44
TC 4
Z9 4
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 7
PY 2014
VL 9
IS 2
AR e87807
DI 10.1371/journal.pone.0087807
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA1CR
UT WOS:000330834400018
PM 24516563
ER
PT J
AU Van Engelenburg, SB
Shtengel, G
Sengupta, P
Waki, K
Jarnik, M
Ablan, SD
Freed, EO
Hess, HF
Lippincott-Schwartz, J
AF Van Engelenburg, Schuyler B.
Shtengel, Gleb
Sengupta, Prabuddha
Waki, Kayoko
Jarnik, Michal
Ablan, Sherimay D.
Freed, Eric O.
Hess, Harald F.
Lippincott-Schwartz, Jennifer
TI Distribution of ESCRT Machinery at HIV Assembly Sites Reveals Virus
Scaffolding of ESCRT Subunits
SO SCIENCE
LA English
DT Article
ID CYTOKINESIS; DYNAMICS; PROTEIN; COMPLEX; ABSCISSION; FILAMENTS; MIDBODY;
RELEASE; TSG101; VPS4
AB The human immunodeficiency virus (HIV) hijacks the endosomal sorting complexes required for transport (ESCRT) to mediate virus release from infected cells. The nanoscale organization of ESCRT machinery necessary for mediating viral abscission is unclear. Here, we applied three-dimensional superresolution microscopy and correlative electron microscopy to delineate the organization of ESCRT components at HIV assembly sites. We observed ESCRT subunits localized within the head of budding virions and released particles, with head-localized levels of CHMP2A decreasing relative to Tsg101 and CHMP4B upon virus abscission. Thus, the driving force for HIV release may derive from initial scaffolding of ESCRT subunits within the viral bud interior followed by plasma membrane association and selective remodeling of ESCRT subunits.
C1 [Van Engelenburg, Schuyler B.; Sengupta, Prabuddha; Jarnik, Michal; Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA.
[Shtengel, Gleb; Hess, Harald F.] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
[Waki, Kayoko; Ablan, Sherimay D.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Ctr Canc Res,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Lippincott-Schwartz, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA.
EM lippincj@mail.nih.gov
FU Howard Hughes Medical Institute; Intramural NIH HHS [Z99 HD999999]
NR 20
TC 56
Z9 56
U1 1
U2 48
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD FEB 7
PY 2014
VL 343
IS 6171
BP 653
EP 656
DI 10.1126/science.1247786
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CB7QC
UT WOS:000349821400001
PM 24436186
ER
PT J
AU Portnoy, DB
Kaufman, AR
Klein, WMP
Doyle, TA
de Groot, M
AF Portnoy, David B.
Kaufman, Annette R.
Klein, William M. P.
Doyle, Todd A.
de Groot, Mary
TI Cognitive and affective perceptions of vulnerability as predictors of
exercise intentions among people with type 2 diabetes
SO JOURNAL OF RISK RESEARCH
LA English
DT Article
DE risk perception; worry; cognitive; affective; exercise; diabetes
ID CORONARY-HEART-DISEASE; BREAST-CANCER RISK; PROTECTION MOTIVATION
THEORY; HEALTH BELIEF MODEL; PERCEIVED RISK; WOMENS PERCEPTIONS;
PERSONAL RISK; WORRY; BEHAVIOR; METAANALYSIS
AB Most conventional measures of risk perception such as perceived likelihood address largely deliberative or cognitive perceptions of vulnerability. Nevertheless, affective perceptions of vulnerability such as worry may have different antecedents and consequences than do these conventional measures, serve as stronger predictors of behavior, and qualify effects of conventional deliberative risk perceptions on behavior. In this study, we assessed how worry - the most common measure of affective perceptions of vulnerability compared with three conventional measures of risk (absolute risk, comparative risk, and conditional risk) in predicting behavioral intentions. Participants were 83 adults with type 2 diabetes who assessed their risk of heart disease and reported their intentions to increase physical activity (which reduces heart disease risk). As predicted, worry was the only significant predictor of exercise intentions such that higher worry was associated with higher intentions. Importantly, this relationship was stronger among individuals who perceived their absolute risk to be relatively higher and those who perceived their comparative risk to be relatively lower, demonstrating that cognitive and affective perceptions interact. These findings highlight the importance of not conflating affective and cognitive perceptions of vulnerability when assessing perceived risk and suggest the need for more research on how to best conceptualize perceived risk in different samples and settings.
C1 [Portnoy, David B.; Kaufman, Annette R.; Klein, William M. P.] NCI, Behav Res Program, Rockville, MD 20852 USA.
[Portnoy, David B.] NCI, Canc Prevent Fellowship Program, Rockville, MD USA.
[Klein, William M. P.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA.
[Doyle, Todd A.] Ohio Univ, Dept Psychol, Athens, OH 45701 USA.
[de Groot, Mary] Indiana Univ, Sch Med, Indianapolis, IN USA.
RP Portnoy, DB (reprint author), NCI, Behav Res Program, Rockville, MD 20852 USA.
EM david.portnoy@fda.hhs.gov
OI Portnoy, David/0000-0003-2175-9457
FU NIDDK NIH HHS [P30 DK092949, R18 DK092765, R34 DK071545]
NR 58
TC 5
Z9 5
U1 2
U2 29
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1366-9877
EI 1466-4461
J9 J RISK RES
JI J. Risk Res.
PD FEB 7
PY 2014
VL 17
IS 2
BP 177
EP 193
DI 10.1080/13669877.2013.794153
PG 17
WC Social Sciences, Interdisciplinary
SC Social Sciences - Other Topics
GA 272MR
UT WOS:000328465400002
PM 24563609
ER
PT J
AU Spinner, MA
Sanchez, LA
Hsu, AP
Shaw, PA
Zerbe, CS
Calvo, KR
Arthur, DC
Gu, WJ
Gould, CM
Brewer, CC
Cowen, EW
Freeman, AF
Olivier, KN
Uzel, G
Zelazny, AM
Daub, JR
Spalding, CD
Claypool, RJ
Giri, NK
Alter, BP
Mace, EM
Orange, JS
Cuellar-Rodriguez, J
Hickstein, DD
Holland, SM
AF Spinner, Michael A.
Sanchez, Lauren A.
Hsu, Amy P.
Shaw, Pamela A.
Zerbe, Christa S.
Calvo, Katherine R.
Arthur, Diane C.
Gu, Wenjuan
Gould, Christine M.
Brewer, Carmen C.
Cowen, Edward W.
Freeman, Alexandra F.
Olivier, Kenneth N.
Uzel, Gulbu
Zelazny, Adrian M.
Daub, Janine R.
Spalding, Christine D.
Claypool, Reginald J.
Giri, Neelam K.
Alter, Blanche P.
Mace, Emily M.
Orange, Jordan S.
Cuellar-Rodriguez, Jennifer
Hickstein, Dennis D.
Holland, Steven M.
TI GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and
immunity
SO BLOOD
LA English
DT Article
ID TRANSCRIPTION FACTOR GATA-2; ACUTE MYELOID-LEUKEMIA; FAMILIAL
MYELODYSPLASTIC SYNDROME; NATURAL-KILLER-CELLS; HUMAN BREAST-TUMORS;
MONOMAC SYNDROME; SPORADIC MONOCYTOPENIA; AUTOSOMAL-DOMINANT; PRIMARY
LYMPHEDEMA; GENE-EXPRESSION
AB Haploinsufficiency of the hematopoietic transcription factor GATA2 underlies monocytopenia and mycobacterial infections; dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency; familial myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML); and Emberger syndrome (primary lymphedema with MDS). A comprehensive examination of the clinical features of GATA2 deficiency is currently lacking. We reviewed the medical records of 57 patients with GATA2 deficiency evaluated at the National Institutes of Health from January 1, 1992, to March 1, 2013, and categorized mutations as missense, null, or regulatory to identify genotype-phenotype associations. We identified a broad spectrum of disease: hematologic (MDS 84%, AML 14%, chronic myelomonocytic leukemia 8%), infectious (severe viral 70%, disseminated mycobacterial 53%, and invasive fungal infections 16%), pulmonary (diffusion 79% and ventilatory defects 63%, pulmonary alveolar proteinosis 18%, pulmonary arterial hypertension 9%), dermatologic (warts 53%, panniculitis 30%), neoplastic (human papillomavirus+ tumors 35%, Epstein-Barr virus+ tumors 4%), vascular/lymphatic (venous thrombosis 25%, lymphedema 11%), sensorineural hearing loss 76%, miscarriage 33%, and hypothyroidism 14%. Viral infections and lymphedema were more common in individuals with null mutations (P=.038 and P=.006, respectively). Monocytopenia, B, NK, and CD4 lymphocytopenia correlated with the presence of disease (P<.001). GATA2 deficiency unites susceptibility to MDS/AML, immunodeficiency, pulmonary disease, and vascular/lymphatic dysfunction. Early genetic diagnosis is critical to direct clinical management, preventive care, and family screening.
C1 [Spinner, Michael A.; Sanchez, Lauren A.; Hsu, Amy P.; Zerbe, Christa S.; Freeman, Alexandra F.; Olivier, Kenneth N.; Uzel, Gulbu; Zelazny, Adrian M.; Daub, Janine R.; Spalding, Christine D.; Claypool, Reginald J.; Cuellar-Rodriguez, Jennifer; Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Shaw, Pamela A.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
[Calvo, Katherine R.] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Arthur, Diane C.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Gu, Wenjuan] Frederick Natl Lab Canc Res, Support Biostat Res Branch, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD USA.
[Gould, Christine M.] Walter Reed Natl Mil Med Ctr, Dept Pediat, Bethesda, MD USA.
[Brewer, Carmen C.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, Bethesda, MD USA.
[Cowen, Edward W.] NCI, Dermatol Branch, Bethesda, MD 20892 USA.
[Giri, Neelam K.; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Mace, Emily M.; Orange, Jordan S.] Texas Childrens Hosp, Baylor Coll Med, Ctr Human Immunobiol, Houston, TX 77030 USA.
[Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
RP Holland, SM (reprint author), CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA.
EM smh@nih.gov
OI orange, jordan/0000-0001-7117-7725; Calvo, Katherine/0000-0002-0771-4191
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases; National Cancer Institute
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases and National Cancer
Institute. The content of this publication does not necessarily reflect
the views or policies of the Department of Health and Human Services,
nor does mention of trade names, commercial products, or organizations
imply endorsement by the US Government.
NR 58
TC 104
Z9 104
U1 2
U2 19
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 6
PY 2014
VL 123
IS 6
BP 809
EP 821
DI 10.1182/blood-2013-07-515528
PG 13
WC Hematology
SC Hematology
GA AH0TY
UT WOS:000335834600006
PM 24227816
ER
PT J
AU Tumbale, P
Williams, JS
Schellenberg, MJ
Kunkel, TA
Williams, RS
AF Tumbale, Percy
Williams, Jessica S.
Schellenberg, Matthew J.
Kunkel, Thomas A.
Williams, R. Scott
TI Aprataxin resolves adenylated RNA-DNA junctions to maintain genome
integrity
SO NATURE
LA English
DT Article
ID DISEASE PROTEIN APRATAXIN; RIBONUCLEOTIDE INCORPORATION;
NEURODEGENERATIVE DISEASE; POLYMERASE; MUTATIONS; REMOVAL; REPAIR; GENE;
REPLICATION; SUPERFAMILY
AB Faithful maintenance and propagation of eukaryotic genomes is ensured by three-step DNA ligation reactions used by ATP-dependent DNA ligases(1,2). Paradoxically, when DNA ligases encounter nicked DNA structures with abnormal DNA termini, DNA ligase catalytic activity can generate and/or exacerbate DNA damage through abortive ligation that produces chemically adducted, toxic 5'-adenylated (5'-AMP) DNA lesions(3-6). Aprataxin (APTX) reverses DNA adenylation but the context for deadenylation repair is unclear. Here we examine the importance of APTX to RNase-H2-dependent excision repair (RER) of a lesion that is very frequently introduced into DNA, a ribonucleotide. We show that ligases generate adenylated 5' ends containing a ribose characteristic of RNase H2 incision. APTX efficiently repairs adenylated RNA-DNA, and acting in an RNA-DNA damage response (RDDR), promotes cellular survival and prevents S-phase checkpoint activation in budding yeast undergoing RER. Structure-function studies of human APTX-RNA-DNA-AMP-Zn complexes define a mechanism for detecting and reversing adenylation at RNA-DNA junctions. This involves A-form RNA binding, proper protein folding and conformational changes, all of which are affected by heritable APTX mutations in ataxia with oculomotor apraxia 1. Together, these results indicate that accumulation of adenylated RNA-DNA may contribute to neurological disease.
C1 [Tumbale, Percy; Williams, Jessica S.; Schellenberg, Matthew J.; Kunkel, Thomas A.; Williams, R. Scott] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Williams, Jessica S.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Williams, RS (reprint author), NIEHS, Struct Biol Lab, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM williamsrs@niehs.nih.gov
RI Williams, Robert/A-6059-2015
FU US National Institutes of Health (NIH), National Institute of
Environmental Health Sciences (NIEHS) [1Z01ES102765, Z01ES065070]; US
Department of Energy, Office of Science, Office of Basic Energy Sciences
[W-31-109-Eng-38]
FX This work was supported by the intramural research program of the US
National Institutes of Health (NIH), National Institute of Environmental
Health Sciences (NIEHS) projects 1Z01ES102765 to R.S.W. and Z01ES065070
to T.A.K. X-ray diffraction data were collected at Southeast Regional
Collaborative Access Team (SER-CAT) 22-ID (or 22-BM) beamline at the
Advanced Photon Source, Argonne National Laboratory. Use of the Advanced
Photon Source was supported by the US Department of Energy, Office of
Science, Office of Basic Energy Sciences, under Contract number
W-31-109-Eng-38. We thank L. Pedersen of the NIEHS collaborative
crystallography group, and the Advanced Photon Source (APS) Southeast
Regional Collaborative Access Team (SER-CAT) staff for assistance with
crystallographic data collection. We thank L. Pedersen and B. Wallace
for critical reading of the manuscript, J. Krahn for assistance with
movies, and T. Ellenberger and P. O'Brien for DNA ligase expression
vectors.
NR 38
TC 41
Z9 41
U1 0
U2 19
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 6
PY 2014
VL 506
IS 7486
BP 111
EP +
DI 10.1038/nature12824
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100042
PM 24362567
ER
PT J
AU Kulzer, JR
Stitzel, ML
Morken, MA
Huyghe, JR
Fuchsberger, C
Kuusisto, J
Laakso, M
Boehnke, M
Collins, FS
Mohlke, KL
AF Kulzer, Jennifer R.
Stitzel, Michael L.
Morken, Mario A.
Huyghe, Jeroen R.
Fuchsberger, Christian
Kuusisto, Johanna
Laakso, Markku
Boehnke, Michael
Collins, Francis S.
Mohlke, Karen L.
TI A Common Functional Regulatory Variant at a Type 2 Diabetes Locus
Upregulates ARAP1 Expression in the Pancreatic Beta Cell
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; INSULIN-SECRETION; TRANSCRIPTIONAL REPRESSOR;
GENE-EXPRESSION; SUSCEPTIBILITY LOCUS; ISLET PREPARATIONS; PROVIDES
INSIGHTS; PLASMA-MEMBRANE; PAX4; ARF
AB Genome-wide association studies (GWASs) have identified more than 70 loci associated with type 2 diabetes (T2D), but for most, the underlying causal variants, associated genes, and functional mechanisms remain unknown. At a T2D- and fasting-proinsulin-associated locus on 11q13.4, we have identified a functional regulatory DNA variant, a candidate target gene, and a plausible underlying molecular mechanism. Fine mapping, conditional analyses, and exome array genotyping in 8,635 individuals from the Metabolic Syndrome in Men study confirmed a single major association signal between fasting proinsulin and noncoding variants (p = 7.4 x 10(-5)). Measurement of allele-specific mRNA levels in human pancreatic islet samples heterozygous for rs11603334 showed that the T2D-risk and proinsulin-decreasing allele (C) is associated with increased ARAP1 expression (p < 0.02). We evaluated four candidate functional SNPs for allelic effects on transcriptional activity by performing reporter assays in rodent pancreatic beta cell lines. The C allele of rs11603334, located near one of the ARAPI promoters, exhibited 2-fold higher transcriptional activity than did the T allele (p < 0.0001); three other candidate SNPs showed no allelic differences. Electrophoretic mobility shift assays demonstrated decreased binding of pancreatic beta cell transcriptional regulators PAX6 and PAX4 to the rs11603334 C allele. Collectively, these data suggest that the T2D-risk allele of rs11603334 could abrogate binding of a complex containing PAX6 and PAX4 and thus lead to increased promoter activity and ARAP1 expression in human pancreatic islets. This work suggests that increased ARAP1 expression might contribute to T2D susceptibility at this GWAS locus.
C1 [Kulzer, Jennifer R.; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Stitzel, Michael L.; Morken, Mario A.; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Stitzel, Michael L.] Jackson Lab Genom Med, Farmington, CT 06030 USA.
[Huyghe, Jeroen R.; Fuchsberger, Christian; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Huyghe, Jeroen R.; Fuchsberger, Christian; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.
[Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
RP Mohlke, KL (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
EM mohlke@med.unc.edu
OI Fuchsberger, Christian/0000-0002-5918-8947
FU National Institutes of Health (NIH) [R01DK072193, R21DA027040,
R01DK093757, K99DK092251, R01DK062370]; NIH National Human Genome
Research Institute (NHGRI) Division of Intramural Research project
[Z01HG000024]; Academy of Finland [77299, 124243]
FX We thank first and foremost the human organ donors whose pancreatic
islets were used in this study. Islets were obtained from the Islet Cell
Resource Center Basic Science Islet Distribution Program and Integrated
Islet Distribution Program and the National Disease Research
Interchange. This study was supported by National Institutes of Health
(NIH) grants R01DK072193 (K.L.M.), R21DA027040 (K.L.M.), R01DK093757
(K.L.M.), K99DK092251 (M.L.S.), and R01DK062370 (M.B.), NIH National
Human Genome Research Institute (NHGRI) Division of Intramural Research
project number Z01HG000024 (F.S.C.), and Academy of Finland grants 77299
and 124243 (M.L.). The authors gratefully acknowledge the Genetics of
Type 2 Diabetes Consortium for access to the reference Panel used for
imputation, Michael R. Erdos (NHGRI) for assistance coordinating and
preparing human islet samples, Yun Li (University of North Carolina at
Chapel Hill) for providing linkage-disequilibrium data from the 1000
Genomes Project, Praveen Sethupathy (University of North Carolina at
Chapel Hill) for helpful discussion and assistance generating motif
prediction scores via PWM-Scan, Leslie Lange and Ethan Lange (University
of North Carolina at Chapel Hill) for statistical advice, and Marie
Fogarty (University of North Carolina at Chapel Hill) for helpful
discussions.
NR 66
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD FEB 6
PY 2014
VL 94
IS 2
BP 186
EP 197
DI 10.1016/j.ajhg.2013.12.011
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA AA9NF
UT WOS:000331419500003
PM 24439111
ER
PT J
AU Peloso, GM
Auer, PL
Bis, JC
Voorman, A
Morrison, AC
Stitziel, NO
Brody, JA
Khetarpal, SA
Crosby, JR
Fomage, M
Isaacs, A
Jakobsdottir, J
Feitosa, MF
Davies, G
Huffman, JE
Manichaikul, A
Davis, B
Lohman, K
Joon, AY
Smith, AV
Grove, ML
Zanoni, P
Redon, V
Demissie, S
Lawson, K
Peters, U
Carlson, C
Jackson, RD
Ryckman, KK
Mackey, RH
Robinson, JG
Siscovick, DS
Schreiner, PJ
Mychaleckyj, JC
Pankow, JS
Holman, A
Uitterlinden, AG
Harris, TB
Taylor, KD
Stafford, JM
Reynolds, LM
Marioni, RE
Dehghan, A
Franco, OH
Patele, AP
Lu, YC
Hindy, G
Gottesman, O
Bottinger, EP
Melander, O
Orho-Melander, M
Loos, RJF
Duga, S
Merlini, PA
Farrall, M
Goel, A
Asselta, R
Girelli, D
Martinelli, N
Shah, SH
Kraus, WE
Li, MY
Rader, DJ
Reilly, MP
McPherson, R
Watkins, H
Ardissino, D
Zhang, QY
Wang, JD
Tsai, MY
Taylor, HA
Correa, A
Griswold, ME
Lange, LA
Starr, JM
Rudan, I
Eiriksdottir, G
Launer, LJ
Ordovas, JM
Levy, D
Chen, YDI
Reiner, AP
Hayward, C
Polasek, O
Deary, IJ
Borecki, IB
Liu, YM
Gudnason, V
Wilson, JG
van Duijn, CM
Kooperberg, C
Rich, SS
Psaty, BM
Rotter, JI
O'Donnell, CJ
Rice, K
Boerwinkle, E
Kathiresan, S
Cupples, LA
AF Peloso, Gina M.
Auer, Paul L.
Bis, Joshua C.
Voorman, Arend
Morrison, Alanna C.
Stitziel, Nathan O.
Brody, Jennifer A.
Khetarpal, Sumeet A.
Crosby, Jacy R.
Fomage, Myriam
Isaacs, Aaron
Jakobsdottir, Johanna
Feitosa, Mary F.
Davies, Gail
Huffman, Jennifer E.
Manichaikul, Ani
Davis, Brian
Lohman, Kurt
Joon, Aron Y.
Smith, Albert V.
Grove, Megan L.
Zanoni, Paolo
Redon, Valeska
Demissie, Serkalem
Lawson, Kim
Peters, Ulrike
Carlson, Christopher
Jackson, Rebecca D.
Ryckman, Kelli K.
Mackey, Rachel H.
Robinson, Jennifer G.
Siscovick, David S.
Schreiner, Pamela J.
Mychaleckyj, Josyf C.
Pankow, James S.
Holman, Albert
Uitterlinden, Andre G.
Harris, Tamara B.
Taylor, Kent D.
Stafford, Jeanette M.
Reynolds, Lindsay M.
Marioni, Riccardo E.
Dehghan, Abbas
Franco, Oscar H.
Patele, Aniruddh P.
Lu, Yingchang
Hindy, George
Gottesman, Omri
Bottinger, Erwin P.
Melander, Olle
Orho-Melander, Marju
Loos, Ruth J. F.
Duga, Stefano
Merlini, Piera Angelica
Farrall, Martin
Goel, Anuj
Asselta, Rosanna
Girelli, Domenico
Martinelli, Nicola
Shah, Svati H.
Kraus, William E.
Li, Mingyao
Rader, Daniel J.
Reilly, Muredach P.
McPherson, Ruth
Watkins, Hugh
Ardissino, Diego
Zhang, Qunyuan
Wang, Judy
Tsai, Michael Y.
Taylor, Herman A.
Correa, Adolfo
Griswold, Michael E.
Lange, Leslie A.
Starr, John M.
Rudan, Igor
Eiriksdottir, Gudny
Launer, Lenore J.
Ordovas, Jose M.
Levy, Daniel
Chen, Y. -D. Ida
Reiner, Alexander P.
Hayward, Caroline
Polasek, Ozren
Deary, Ian J.
Borecki, Ingrid B.
Liu, Yongmei
Gudnason, Vilmundur
Wilson, James G.
van Duijn, Cornelia M.
Kooperberg, Charles
Rich, Stephen S.
Psaty, Bruce M.
Rotter, Jerome I.
O'Donnell, Christopher J.
Rice, Kenneth
Boerwinkle, Eric
Kathiresan, Sekar
Cupples, L. Adrienne
CA NHLBI GO Exome Sequencing Project
TI Association of Low-Frequency and Rare Coding-Sequence Variants with
Blood Lipids and Coronary Heart Disease in 56,000 Whites and Blacks
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID PLATELET-ACTIVATING-FACTOR; DENSITY-LIPOPROTEIN CHOLESTEROL; FACTOR
ACETYLHYDROLASES; PCSK9; PROTEIN; TRAITS; LDL
AB Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121*], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.
C1 [Peloso, Gina M.; Patele, Aniruddh P.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Peloso, Gina M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Peloso, Gina M.; O'Donnell, Christopher J.; Kathiresan, Sekar] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA.
[Peloso, Gina M.; Patele, Aniruddh P.; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Auer, Paul L.; Peters, Ulrike; Carlson, Christopher; Reiner, Alexander P.; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA.
[Auer, Paul L.] Univ Wisconsin, Sch Publ Hlth, Milwaukee, WI 53201 USA.
[Bis, Joshua C.; Brody, Jennifer A.; Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA.
[Voorman, Arend; Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Morrison, Alanna C.; Crosby, Jacy R.; Fomage, Myriam; Davis, Brian; Grove, Megan L.; Lawson, Kim; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.
[Stitziel, Nathan O.] Washington Univ, Sch Med, Div Cardiovasc, Dept Med, St Louis, MO 63110 USA.
[Stitziel, Nathan O.; Feitosa, Mary F.; Zhang, Qunyuan; Wang, Judy; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
[Khetarpal, Sumeet A.; Zanoni, Paolo; Redon, Valeska; Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Crosby, Jacy R.] Univ Texas Grad Sch Biomed Sci Houston, Dept Biostat Bioinformat & Syst Biol, Houston, TX 77030 USA.
[Fomage, Myriam; Joon, Aron Y.] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
[Isaacs, Aaron; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, NL-3015 CN Rotterdam, Netherlands.
[Jakobsdottir, Johanna; Smith, Albert V.; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland.
[Davies, Gail; Marioni, Riccardo E.; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Davies, Gail; Marioni, Riccardo E.; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Huffman, Jennifer E.; Hayward, Caroline] Univ Edinburgh, MRC IGMM, MRC Human Genet, Edinburgh EH4 2XU, Midlothian, Scotland.
[Manichaikul, Ani; Mychaleckyj, Josyf C.; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
[Manichaikul, Ani; Mychaleckyj, Josyf C.; Rich, Stephen S.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
[Lohman, Kurt; Stafford, Jeanette M.; Reynolds, Lindsay M.; Liu, Yongmei] Wake Forest Sch Med, Winston Salem, NC 27106 USA.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
[Demissie, Serkalem; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Demissie, Serkalem; Levy, Daniel; O'Donnell, Christopher J.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol Diabet & Metab, Dept Internal Med, Columbus, OH 43210 USA.
[Ryckman, Kelli K.; Robinson, Jennifer G.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA.
[Mackey, Rachel H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Siscovick, David S.; Reiner, Alexander P.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Schreiner, Pamela J.; Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, Minneapolis, MN 55454 USA.
[Holman, Albert; Uitterlinden, Andre G.; Dehghan, Abbas; Franco, Oscar H.] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands.
[Harris, Tamara B.; Launer, Lenore J.] NIA, NIH, Bethesda, MD 20892 USA.
[Taylor, Kent D.; Chen, Y. -D. Ida; Rotter, Jerome I.] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles BioMed Res Inst, Torrance, CA 90502 USA.
[Patele, Aniruddh P.] Yale Univ, Sch Med, New Haven, CT 06510 USA.
[Lu, Yingchang; Gottesman, Omri; Bottinger, Erwin P.; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
[Lu, Yingchang; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
[Hindy, George; Melander, Olle] Lund Univ, Dept Clin Sci Malmo, Clin Res Ctr, S-20502 Malmo, Sweden.
[Orho-Melander, Marju] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, S-20502 Malmo, Sweden.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
[Duga, Stefano; Asselta, Rosanna] Univ Milan, Dipartimento Biotecnol Med & Med Traslaz, I-20133 Milan, Italy.
[Merlini, Piera Angelica; Ardissino, Diego] ASTC, I-27100 Pavia, Italy.
[Merlini, Piera Angelica] Osped Maggiore Niguarda, Div Cardiol, I-20162 Milan, Italy.
[Farrall, Martin; Goel, Anuj; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Dept Cardiovasc Med, Oxford OX3 7BN, England.
[Girelli, Domenico; Martinelli, Nicola] Univ Verona, Sch Med, Dept Med, I-37134 Verona, Italy.
[Shah, Svati H.] Duke Univ, Div Urogynecol, Dept Obstet & Gynecol, Durham, NC 27710 USA.
[Shah, Svati H.; Kraus, William E.] Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27710 USA.
[Kraus, William E.] Duke Univ, Sch Med, Duke Mol Physiol Inst, Durham, NC 27701 USA.
[Li, Mingyao] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[McPherson, Ruth] Univ Ottawa, Inst Heart, Div Cardiol, Atherogen Lab, Ottawa, ON K1Y 4W7, Canada.
[Watkins, Hugh] Merck Sharp & Dohme Corp, Rahway, NJ 07065 USA.
[Ardissino, Diego] Azienda Osped Univ Parma, Div Cardiol, I-43100 Parma, Italy.
[Tsai, Michael Y.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55454 USA.
[Taylor, Herman A.] Jackson State Univ, Jackson, MS 39217 USA.
[Taylor, Herman A.] Tougaloo Coll, Tougaloo, MS 39174 USA.
[Taylor, Herman A.; Correa, Adolfo; Griswold, Michael E.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Rudan, Igor] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland.
[Rudan, Igor] Univ Split, Croatian Ctr Global Hlth, Fac Med, Split 21000, Croatia.
[Ordovas, Jose M.] Natl Ctr Cardiovasc Investigat, Dept Cardiovasc Epidemiol & Populat Genet, Madrid 28049, Spain.
[Ordovas, Jose M.] IMDEA Alimentac, Madrid 28049, Spain.
[Ordovas, Jose M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr & Genom Lab, Medford, MA 02155 USA.
[Ordovas, Jose M.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Polasek, Ozren] Univ Split, Fac Med, Dept Publ Hlth, Split 21000, Croatia.
[Wilson, James G.] Univ Mississippi, Dept Physiol & Biophys, Med Ctr, Jackson, MS 39216 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[O'Donnell, Christopher J.; Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM skathiresan@partners.org; skathiresan@partners.org; adrienne@bu.edu
RI Hindy, George/H-1864-2016; Duga, Stefano/F-8173-2014; Gudnason,
Vilmundur/K-6885-2015; Polasek, Ozren/B-6002-2011; Rudan,
Igor/I-1467-2012; Smith, Albert/K-5150-2015; Martinelli,
Nicola/J-5622-2016; Hayward, Caroline/M-8818-2016; Feitosa,
Mary/K-8044-2012;
OI Mackey, Rachel/0000-0001-6088-2664; Hindy, George/0000-0002-7257-9299;
Stitziel, Nathan/0000-0002-4963-8211; Manichaikul,
Ani/0000-0002-5998-795X; Duga, Stefano/0000-0003-3457-1410; Watkins,
Hugh/0000-0002-5287-9016; Pankow, James/0000-0001-7076-483X; Dehghan,
Abbas/0000-0001-6403-016X; Gudnason, Vilmundur/0000-0001-5696-0084;
Polasek, Ozren/0000-0002-5765-1862; Rudan, Igor/0000-0001-6993-6884;
Smith, Albert/0000-0003-1942-5845; Martinelli,
Nicola/0000-0001-6465-5119; Hayward, Caroline/0000-0002-9405-9550;
Feitosa, Mary/0000-0002-0933-2410; Asselta, Rosanna/0000-0001-5351-0619;
Reynolds, Lindsay/0000-0001-6157-0144
FU National Heart, Lung, and Blood Institute (NHLBI); NHLBI [RC2 HL-103010,
RC2 HL-102923, RC2 HL-102924, RC2 HL-102925, RC2 HL-102926,
T32HL007208]; National Heart, Lung, and Blood Institute [HL105756];
Massachusetts General Hospital (MGH); Howard Goodman Fellowship from
MGH; Donovan Family Foundation [R01HL107816]; Fondation Leducq; NIH [RC2
HL-102925]; Merck; NIH/NHLBI [K08-HL114642]; NWO grant (veni)
[916.12.154]; EUR Fellowship
FX The authors wish to acknowledge the support of the National Heart, Lung,
and Blood Institute (NHLBI) and the contributions of the research
institutions, study investigators, field staff, and study participants
in creating this resource for biomedical research. Funding for GO ESP
was provided by NHLBI grants RC2 HL-103010 (HeartGO), RC2 HL-102923
(LungGO), and RC2 HL-102924 (WHISP). The exome sequencing was performed
through NHLBI grants RC2 HL-102925 (BroadGO) and RC2 HL-102926
(SeattleGO). Infrastructure for the CHARGE Consortium is supported, in
part, by the National Heart, Lung, and Blood Institute (grant HL105756).
G.M.P. is supported by award number T32HL007208 from the NHLBI. S.K. is
supported by a Research Scholar award from the Massachusetts General
Hospital (MGH), the Howard Goodman Fellowship from MGH, the Donovan
Family Foundation, R01HL107816, and a grant from Fondation Leducq. Exome
Array genotyping in case-control studies of coronary heart disease was
supported by NIH RC2 HL-102925 and an investigator-initiated research
grant from Merck to S.K. N.O.S. is supported, in part, by a career
development award from the NIH/NHLBI K08-HL114642. A.D. is supported by
NWO grant (veni, 916.12.154) and the EUR Fellowship. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the NHLBI or NIH. A full listing of
acknowledgements is provided in Supplemental Data.
NR 28
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U1 2
U2 23
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD FEB 6
PY 2014
VL 94
IS 2
BP 223
EP 232
DI 10.1016/j.ajhg.2014.01.009
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA AA9NF
UT WOS:000331419500006
PM 24507774
ER
PT J
AU Lange, LA
Hu, YN
Zhang, H
Xue, CY
Schmidt, EM
Tang, ZZ
Bizon, C
Lange, EM
Smith, JD
Turner, EH
Jun, G
Kang, HM
Peloso, G
Auer, P
Li, KP
Flannick, J
Zhang, J
Fuchsberger, C
Gaulton, K
Lindgren, C
Locke, A
Manning, A
Sim, XL
Rivas, MA
Holmen, OL
Gottesman, O
Lu, YC
Ruderfer, D
Stah, EA
Duan, Q
Li, Y
Durda, P
Jiao, S
Isaacs, A
Hofman, A
Bis, JC
Correa, A
Griswold, ME
Jakobsdottir, J
Smith, AV
Schreiner, PJ
Feitosa, ME
Zhang, QY
Huffman, JE
Crosby, J
Wasse, CL
Do, R
Franceschini, N
Martin, LW
Robinson, JG
Assimes, TL
Crosslin, DR
Rosenthal, EA
Tsai, M
Rieder, MJ
Farlow, DN
Folsom, AR
Lumley, T
Fox, ER
Carlson, CS
Peters, U
Jackson, RD
Van Duijn, CM
Uitterlinden, AG
Levy, D
Rotter, JI
Taylor, HA
Gudnason, V
Siscovick, DS
Fornage, M
Borecki, IB
Hayward, C
Rudan, I
Chen, YE
Bottinger, EP
Loos, RJF
Strom, P
Hveem, K
Boehnke, M
Groop, L
McCarthy, M
Meitinger, T
Ballantyne, CM
Gabriel, SB
O'Donne, CJ
Post, WS
North, KE
Reiner, AP
Boerwinkle, E
Psaty, BM
Altshuler, D
Kathiresan, S
Lin, DY
Jarvik, GP
Cupples, LA
Kooperberg, C
Wilson, JG
Nickerson, DA
Abecasis, GR
Rich, SS
Tracy, RP
Willer, CJ
AF Lange, Leslie A.
Hu, Youna
Zhang, He
Xue, Chenyi
Schmidt, Ellen M.
Tang, Zheng-Zheng
Bizon, Chris
Lange, Ethan M.
Smith, Joshua D.
Turner, Emily H.
Jun, Goo
Kang, Hyun Min
Peloso, Gina
Auer, Paul
Li, Kuo-Ping
Flannick, Jason
Zhang, Ji
Fuchsberger, Christian
Gaulton, Kyle
Lindgren, Cecilia
Locke, Adam
Manning, Alisa
Sim, Xueling
Rivas, Manuel A.
Holmen, Oddgeir L.
Gottesman, Omri
Lu, Yingchang
Ruderfer, Douglas
Stah, Eli A.
Duan, Qing
Li, Yun
Durda, Peter
Jiao, Shuo
Isaacs, Aaron
Hofman, Albert
Bis, Joshua C.
Correa, Adolfo
Griswold, Michael E.
Jakobsdottir, Johanna
Smith, Albert V.
Schreiner, Pamela J.
Feitosa, Mary E.
Zhang, Qunyuan
Huffman, Jennifer E.
Crosby, Jacy
Wasse, Christina L.
Do, Ron
Franceschini, Nora
Martin, Lisa W.
Robinson, Jennifer G.
Assimes, Themistocles L.
Crosslin, David R.
Rosenthal, Elisabeth A.
Tsai, Michael
Rieder, Mark J.
Farlow, Deborah N.
Folsom, Aaron R.
Lumley, Thomas
Fox, Ervin R.
Carlson, Christopher S.
Peters, Ulrike
Jackson, Rebecca D.
Van Duijn, Cornelia M.
Uitterlinden, Andre G.
Levy, Daniel
Rotter, Jerome I.
Taylor, Herman A.
Gudnason, Vilmundur, Jr.
Siscovick, David S.
Fornage, Myriam
Borecki, Ingrid B.
Hayward, Caroline
Rudan, Igor
Chen, Y. Eugene
Bottinger, Erwin P.
Loos, Ruth J. F.
Strom, Pal
Hveem, Kristian
Boehnke, Michael
Groop, Leif
McCarthy, Mark
Meitinger, Thomas
Ballantyne, Christie M.
Gabriel, Stacey B.
O'Donne, Christopher J.
Post, Wendy S.
North, Kari E.
Reiner, Alexander P.
Boerwinkle, Eric
Psaty, Bruce M.
Altshuler, David
Kathiresan, Sekar
Lin, Dan-Yu
Jarvik, Gail P.
Cupples, L. Adrienne
Kooperberg, Charles
Wilson, James G.
Nickerson, Deborah A.
Abecasis, Goncalo R.
Rich, Stephen S.
Tracy, Russell P.
Willer, Cristen J.
CA NHLBI Grand Opportunity Exome Sequ
TI Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants
Associated with LDL Cholesterol
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID DENSITY-LIPOPROTEIN-CHOLESTEROL; HEART-DISEASE; DESIGN; PLASMA;
OBJECTIVES; ATHEROSCLEROSIS; SUSCEPTIBILITY; ABSORPTION; SPECTRUM; RISK
AB Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98th or <2nd percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.
C1 [Lange, Leslie A.; Lange, Ethan M.; Duan, Qing; Li, Yun] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Hu, Youna; Jun, Goo; Kang, Hyun Min; Li, Kuo-Ping; Fuchsberger, Christian; Locke, Adam; Sim, Xueling; Boehnke, Michael; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Zhang, He; Zhang, Ji; Chen, Y. Eugene; Willer, Cristen J.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Xue, Chenyi; Schmidt, Ellen M.; Willer, Cristen J.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Tang, Zheng-Zheng; Lange, Ethan M.; Li, Yun; Lin, Dan-Yu] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
[Bizon, Chris] Renaissance Comp Inst, Chapel Hill, NC 27517 USA.
[Smith, Joshua D.; Turner, Emily H.; Rieder, Mark J.; Jarvik, Gail P.; Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Peloso, Gina; Do, Ron; Altshuler, David; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Peloso, Gina; Manning, Alisa; Do, Ron; Gabriel, Stacey B.; Altshuler, David; Kathiresan, Sekar] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02141 USA.
[Auer, Paul; Jiao, Shuo; Carlson, Christopher S.; Peters, Ulrike; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Auer, Paul; Manning, Alisa] Univ Wisconsin, Sch Publ Hlth, Milwaukee, WI 53201 USA.
[Flannick, Jason; Manning, Alisa; Farlow, Deborah N.] Broad Inst Harvard & MIT, Cambridge, MA 02141 USA.
[Flannick, Jason; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Gaulton, Kyle; Lindgren, Cecilia; Rivas, Manuel A.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England.
[Manning, Alisa; Altshuler, David] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02138 USA.
[Holmen, Oddgeir L.; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth, HUNT Res Ctr, N-7600 Levanger, Norway.
[Gottesman, Omri; Bottinger, Erwin P.] Charles Bronfman Inst Personalized Med, Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Lu, Yingchang; Loos, Ruth J. F.] Charles Bronfman Inst Personalized Med, Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
[Ruderfer, Douglas; Stah, Eli A.] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY 10029 USA.
[Li, Yun] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA.
[Durda, Peter; Tracy, Russell P.] Univ Vermont, Dept Pathol, Colchester, VT 05446 USA.
[Isaacs, Aaron; Van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, NL-3015 DR Rotterdam, Netherlands.
[Hofman, Albert] Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands.
[Bis, Joshua C.; Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Correa, Adolfo; Griswold, Michael E.; Fox, Ervin R.; Taylor, Herman A.] Univ Mississippi Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Jakobsdottir, Johanna; Smith, Albert V.; Gudnason, Vilmundur, Jr.] Iceland Heart Assoc, IS-201 Kopavogur, Iceland.
[Smith, Albert V.; Gudnason, Vilmundur, Jr.] Univ Iceland, IS-101 Reykjavik, Iceland.
[Schreiner, Pamela J.; Tsai, Michael; Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA.
[Feitosa, Mary E.; Zhang, Qunyuan; Borecki, Ingrid B.] Washington Univ, Div Stat Genom, Dept Genet, Sch Med, St Louis, MO 63110 USA.
[Huffman, Jennifer E.; Hayward, Caroline] Univ Edinburgh, Med Res Ctr Human Genet, Med Res Ctr Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland.
[Crosby, Jacy; Fornage, Myriam; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Wasse, Christina L.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Martin, Lisa W.] George Washington Sch Med & Hlth Sci, Div Cardiol, Washington, DC 20037 USA.
[Robinson, Jennifer G.] Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA.
[Robinson, Jennifer G.] Univ Iowa, Dept Med, Iowa City, IA 52242 USA.
[Assimes, Themistocles L.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Crosslin, David R.; Rosenthal, Elisabeth A.; Jarvik, Gail P.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
[Crosslin, David R.; Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1142, New Zealand.
[Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol, Columbus, OH 43210 USA.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3000 DR Rotterdam, Netherlands.
[Levy, Daniel; O'Donne, Christopher J.; Cupples, L. Adrienne] NHLBI, Ctr Populat Studies, Framingham, MA 01702 USA.
[Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Rotter, Jerome I.] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles BioMed Res Inst, Torrance, CA 90502 USA.
[Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA.
[Taylor, Herman A.] Tougaloo Coll, Jackson, MS 39174 USA.
[Taylor, Herman A.] Jackson State Univ, Jackson, MS 39217 USA.
[Siscovick, David S.; Reiner, Alexander P.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Med, Med Ctr, Seattle, WA 98195 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
[Rudan, Igor] Univ Edinburgh, Ctr Populat Hlth Sci, Sch Med, Edinburgh EH8 9YL, Midlothian, Scotland.
[Strom, Pal] Norwegian Univ Sci & Technol, Dept Comp & Informat Sci, N-7491 Trondheim, Norway.
[Strom, Pal] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, N-7489 Trondheim, Norway.
[Groop, Leif] Lund Univ, Dept Clin Sci Diabet & Endocrinol, Skane Univ Hosp, S-22100 Malmo, Sweden.
[Groop, Leif] Glostrup Univ Hosp, Glostrup Res Inst, DK-2600 Glostrup, Denmark.
[McCarthy, Mark] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX1 2JD, England.
[McCarthy, Mark] Univ Oxford, Churchill Hosp, Oxford Natl Inst Hlth Res Biomed Res Ctr, Oxford OX1 2JD, England.
[Meitinger, Thomas] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Human Genet, D-85764 Neuherberg, Germany.
[Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, D-85764 Neuherberg, Germany.
[Ballantyne, Christie M.] Baylor Coll Med, Houston, TX 77030 USA.
[Ballantyne, Christie M.] Houston Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA.
[O'Donne, Christopher J.; Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Post, Wendy S.] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD 21205 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98195 USA.
[Cupples, L. Adrienne] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
[Tracy, Russell P.] Univ Vermont, Dept Biochem, Burlington, VT 05405 USA.
[Willer, Cristen J.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
RP Willer, CJ (reprint author), Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
EM cristen@umich.edu
RI Johnson, Andrew/G-6520-2013; Feitosa, Mary/K-8044-2012; Jun,
Goo/F-1941-2017; Singleton, Andrew/C-3010-2009; Zhang, Ji/J-4009-2014;
Jarvik, Gail/N-6476-2014; Altshuler, David/A-4476-2009; Hardy,
John/C-2451-2009; Tang, Zheng-Zheng/F-6642-2014; de Bakker,
Paul/B-8730-2009; Gudnason, Vilmundur/K-6885-2015; Meitinger,
Thomas/O-1318-2015; Rudan, Igor/I-1467-2012; Smith, Albert/K-5150-2015;
Ruderfer, Douglas/M-5795-2016; Hayward, Caroline/M-8818-2016
OI Martin, Lisa Warsinger/0000-0003-4352-0914; Locke,
Adam/0000-0001-6227-198X; Turner, Emily/0000-0001-9040-9229; Saetrom,
Pal/0000-0001-8142-7441; Shendure, Jay/0000-0002-1516-1865; Assimes,
Themistocles/0000-0003-2349-0009; Feitosa, Mary/0000-0002-0933-2410;
Jun, Goo/0000-0003-0891-0204; Quinlan, Aaron/0000-0003-1756-0859;
Willer, Cristen/0000-0001-5645-4966; Seshadri,
Sudha/0000-0001-6135-2622; Fuchsberger, Christian/0000-0002-5918-8947;
Jarvik, Gail/0000-0002-6710-8708; Altshuler, David/0000-0002-7250-4107;
Tang, Zheng-Zheng/0000-0003-3802-8087; de Bakker,
Paul/0000-0001-7735-7858; Gudnason, Vilmundur/0000-0001-5696-0084;
Rudan, Igor/0000-0001-6993-6884; Smith, Albert/0000-0003-1942-5845;
Ruderfer, Douglas/0000-0002-2365-386X; Hayward,
Caroline/0000-0002-9405-9550
FU NHLBI [RC2 HL-103010, RC2 HL-102923, RC2 HL-102924, RC2 HL-102925, RC2
HL-102926]; Northwest Institute of Genomic Medicine; Washington State
Life Sciences Discovery Fund; National Institutes of Health
[R01HL107816]; Amarin; Amgen; Astra-Zeneca; Daiichi-Sankyo; Esperion; F.
Hoffman-La Roche; Glaxo-Smith Kline; Merck; Regeneron; Sanofi; Takeda;
Zinfandel; [R01 HL67406]; [R00 HL94535]; [R01 HL109946]
FX The authors wish to acknowledge the support of the NHLBI and the
contributions of the research institutions, study investigators, field
staff, and study participants in creating this resource for biomedical
research. Funding for the NHLBI Grand Opportunity (GO) Exome Sequencing
Project was provided by NHLBI grants RC2 HL-103010 (HeartGO), RC2
HL-102923 (LungGO), and RC2 HL-102924 (Women's Health Initiative
Sequencing Project). Exome sequencing was performed through NHLBI grants
RC2 HL-102925 (BroadGO) and RC2 HL-102926 (SeattleGO). G.J. is supported
by R01 HL67406 and the Northwest Institute of Genomic Medicine, funded
by the Washington State Life Sciences Discovery Fund. S.K.'s effort is
funded through National Institutes of Health grant R01HL107816. C.J.W.
is supported by R00 HL94535 and R01 HL109946. The University of Iowa
receives financial support from Amarin, Amgen, Astra-Zeneca,
Daiichi-Sankyo, Esperion, F. Hoffman-La Roche, Glaxo-Smith Kline, Merck,
Regeneron and Sanofi, and Takeda and Zinfandel for J.G.R's research.
B.M.P serves on the data and safety monitoring board of a clinical trial
for Zoll LifeCor. Additional acknowledgements are provided in the
Supplemental Data.
NR 41
TC 87
Z9 89
U1 2
U2 19
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD FEB 6
PY 2014
VL 94
IS 2
BP 233
EP 245
DI 10.1016/j.ajhg.2014.01.010
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA AA9NF
UT WOS:000331419500007
PM 24507775
ER
PT J
AU Hong, JJ
Feng, HQ
Wang, F
Ranjan, A
Chen, JH
Jiang, JS
Ghirlando, R
Xiao, TS
Wu, C
Bai, YW
AF Hong, Jingjun
Feng, Hanqiao
Wang, Feng
Ranjan, Anand
Chen, Jianhong
Jiang, Jiansheng
Ghirlando, Rodolfo
Xiao, T. Sam
Wu, Carl
Bai, Yawen
TI The Catalytic Subunit of the SWR1 Remodeler Is a Histone Chaperone for
the H2A.Z-H2B Dimer
SO MOLECULAR CELL
LA English
DT Article
ID H2A VARIANT HTZ1; CHROMOSOME STABILITY; CHROMATIN STRUCTURE; STRUCTURAL
BASIS; COMPLEX; NUCLEOSOME; TRANSCRIPTION; RECOGNITION; HETEROCHROMATIN;
HETERODIMER
AB Histone variant H2A.Z-containing nucleosomes exist at most eukaryotic promoters and play important roles in gene transcription and genome stability. The multisubunit nucleosome-remodeling enzyme complex SWR1, conserved from yeast to mammals, catalyzes the ATP-dependent replacement of histone H2A in canonical nucleosomes with H2A.Z. How SWR1 catalyzes the replacement reaction is largely unknown. Here, we determined the crystal structure of the N-terminal region (599-627) of the catalytic subunit Swr1, termed Swr1-Z domain, in complex with the H2A.Z-H2B dimer at 1.78 A resolution. The Swr1-Z domain forms a 3-10 helix and an irregular chain. A conserved LxxLF motif in the Swr1-Z 310 helix specifically recognizes the alpha C helix of H2A.Z. Our results show that the Swr1-Z domain can deliver the H2A.Z-H2B dimer to the DNA-(H3-H4)2 tetrasome to form the nucleosome by a histone chaperone mechanism.
C1 [Hong, Jingjun; Feng, Hanqiao; Wang, Feng; Ranjan, Anand; Chen, Jianhong; Wu, Carl; Bai, Yawen] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Jiang, Jiansheng; Xiao, T. Sam] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Ghirlando, Rodolfo] NIDDK, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
[Wu, Carl] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
RP Bai, YW (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM yawen@helix.nih.gov
RI Xiao, Tsan/A-8590-2010;
OI Xiao, Tsan/0000-0001-9688-475X
FU National Cancer Institute; National Institute of Allergy and Infectious
Diseases; National Institute of Diabetes and Digestive and Kidney
Diseases; National Institutes of Health; Janelia Farm Research Campus of
Howard Hughes Medical Institute; National Cancer Institute [Y1-CO-1020];
National Institute of General Medical Sciences [Y1-GM-1104]; U.S.
Department of Energy [DE-AC02-06CH11357]
FX We thank the staff at the Advanced Photon Source (beamline 23-ID) for
technical support, S. Li for protein purification, D. Wei for
purification of SWR1, Dr. B. Zhou for assistance in ITC data collection
and analysis, and Dr. J. Barrowman for editing the manuscript. This
research was supported by the Intramural Research Programs of the
National Cancer Institute (J.H., H.F., F.W., A.R., J.C., C.W., and
Y.B.), the National Institute of Allergy and Infectious Diseases (J.J.
and T.S.X.), and the National Institute of Diabetes and Digestive and
Kidney Diseases (R.G.), National Institutes of Health, the Janelia Farm
Research Campus of Howard Hughes Medical Institute (C.W.) as well as
National Cancer Institute grant Y1-CO-1020, National Institute of
General Medical Sciences grant Y1-GM-1104, and U.S. Department of Energy
grant DE-AC02-06CH11357 (Advanced Photon Source).
NR 38
TC 20
Z9 21
U1 1
U2 13
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 6
PY 2014
VL 53
IS 3
BP 498
EP 505
DI 10.1016/j.molcel.2014.01.010
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AA2HL
UT WOS:000330915600013
PM 24507717
ER
PT J
AU Fauci, AS
Marston, HD
AF Fauci, Anthony S.
Marston, Hilary D.
TI Ending AIDS - Is an HIV Vaccine Necessary?
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID INFECTION
AB The numbers of AIDS-related deaths and new HIV infections have decreased dramatically, thanks to prevention and treatment tools. But to control the pandemic more quickly and sustain the success, a safe and at least moderately effective vaccine is essential. In the past decade, according to the 2013 Global Report of the Joint United Nations Program on HIV/AIDS (UNAIDS), the numbers of AIDS-related deaths and new human immunodeficiency virus (HIV) infections have fallen by about one third from their peaks accomplishments made possible by the accelerated implementation of effective prevention and treatment tools. Of particular note, the scale-up of antiretroviral therapy (ART) averted 5.4 million deaths in low- and middle-income countries between 1995 and 2012. HIV prevention efforts have expanded from a narrow agenda of providing condoms and clean needles to use of a comprehensive toolkit of preventive interventions ...
C1 [Fauci, Anthony S.; Marston, Hilary D.] NIAID, Off Director, Bethesda, MD 20892 USA.
RP Fauci, AS (reprint author), NIAID, Off Director, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 5
TC 35
Z9 35
U1 3
U2 11
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 6
PY 2014
VL 370
IS 6
BP 495
EP 498
DI 10.1056/NEJMp1313771
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA AA4NT
UT WOS:000331073500004
PM 24499210
ER
PT J
AU Glass, RI
Parashar, UD
AF Glass, Roger I.
Parashar, Umesh D.
TI Rotavirus Vaccines - Balancing Intussusception Risks and Health Benefits
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID UNITED-STATES; VACCINATION; PENTAVALENT; EFFICACY; CHILDREN; MEXICO;
SAFETY
AB In January 2006, the Journal published two landmark articles reporting the safety and efficacy of two different vaccines RotaTeq (Merck), a pentavalent vaccine (RV5),(1) and Rotarix (GlaxoSmithKline), a monovalent vaccine (RV1)(2) to prevent rotavirus, the most common cause of severe childhood diarrhea worldwide and of deaths from diarrhea in low-income countries. Each trial enrolled more than 60,000 infants to determine whether these live oral vaccines caused intussusception, the rare complication that in 1999 forced the withdrawal of the first licensed rotavirus vaccine, RotaShield (Wyeth Lederle), less than a year after it was recommended for routine immunization of U.S. ...
C1 [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Parashar, Umesh D.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
RP Glass, RI (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
NR 14
TC 17
Z9 17
U1 0
U2 5
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 6
PY 2014
VL 370
IS 6
BP 568
EP 570
DI 10.1056/NEJMe1315836
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA AA4NT
UT WOS:000331073500014
PM 24422677
ER
PT J
AU Tripathi, V
Popescu, NC
Zimonjic, DB
AF Tripathi, V.
Popescu, N. C.
Zimonjic, D. B.
TI DLC1 induces expression of E-cadherin in prostate cancer cells through
Rho pathway and suppresses invasion
SO ONCOGENE
LA English
DT Article
DE E-cadherin; DLC1; Rho; invasion; prostate cancer
ID GTPASE-ACTIVATING PROTEIN; EPITHELIAL TUMOR-CELLS;
HEPATOCELLULAR-CARCINOMA; ADHERENS JUNCTIONS; BREAST-CANCER; RHO/ROCK
PATHWAY; GENE-EXPRESSION; FAMILY GTPASES; IN-VIVO; ADHESION
AB E-cadherin is a cell-cell adhesion molecule that acts as a suppressor of cancer cell invasion and its expression is downregulated in many advanced, poorly differentiated, human cancers. In this study, we found that the expression of DLC1 (deleted in liver cancer 1) tumor-suppressor gene in metastatic prostate carcinoma (PCA) cells increased the expression of E-cadherin and resulted in an elevated rate of cell-cell aggregation as measured by aggregation assay. DLC1-mediated increase in E-cadherin expression was not dependent on alpha-catenin, a DLC1-binding protein associated with E-cadherin, and/or cellular density. The increase of E-cadherin expression occurred at mRNA level and relied on DLC1 RhoGAP function, leading to suppression of high level of RhoA-GTP and RhoC-GTP activity in metastatic PCA cells. Application of Rho/ROCK inhibitors produced the same effect as introduction of DLC1. Knocking down of RhoA produced a moderate increase in E-cadherin whereas knocking down of RhoC resulted in a significant increase of E-cadherin. Downregulation of E-cadherin caused by constitutively active RhoA(V14) and RhoC(V14) could not be reversed by expression of DLC1 in DLC1-negative cell line. DLC1-mediated suppression of metastatic PCA cells invasion was comparable with the one associated with ectopic E-cadherin expression, or caused by suppression of Rho pathway either by Rho/ROCK inhibitors, or by shRNA repression. This study demonstrates that DLC1 expression positively regulates E-cadherin and suppresses highly metastatic PCA cell invasion by modulating Rho pathway, which appears as a feasible therapeutic target in cancers with high activity of RhoGTPases.
C1 [Tripathi, V.; Popescu, N. C.; Zimonjic, D. B.] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
RP Popescu, NC (reprint author), NCI, Expt Carcinogenesis Lab, NIH, Bldg 37,Room 4128B,37 Convent Dr,MSC 4262, Bethesda, MD 20892 USA.
EM popescun@mail.nih.gov
FU National Cancer Institute, National Institutes of Health, Bethesda,
Maryland, USA
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health, Bethesda,
Maryland, USA.
NR 57
TC 13
Z9 14
U1 1
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD FEB 6
PY 2014
VL 33
IS 6
BP 724
EP 733
DI 10.1038/onc.2013.7
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA AA5IL
UT WOS:000331129200007
PM 23376848
ER
PT J
AU McCann, CP
Rericha, EC
Wang, CL
Losert, W
Parent, CA
AF McCann, Colin P.
Rericha, Erin C.
Wang, Chenlu
Losert, Wolfgang
Parent, Carole A.
TI Dictyostelium Cells Migrate Similarly on Surfaces of Varying Chemical
Composition
SO PLOS ONE
LA English
DT Article
ID MYOSIN-II; TALIN HOMOLOG; LEADING-EDGE; WILD-TYPE; ADHESION; DISCOIDEUM;
DYNAMICS; MORPHOGENESIS; CYTOKINESIS; SUBSTRATE
AB During cell migration, cell-substrate binding is required for pseudopod anchoring to move the cell forward, yet the interactions with the substrate must be sufficiently weak to allow parts of the cell to de-adhere in a controlled manner during typical protrusion/retraction cycles. Mammalian cells actively control cell-substrate binding and respond to extracellular conditions with localized integrin-containing focal adhesions mediating mechanotransduction. We asked whether mechanotransduction also occurs during non-integrin mediated migration by examining the motion of the social amoeba Dictyostelium discoideum, which is thought to bind non-specifically to surfaces. We discovered that Dictyostelium cells are able to regulate forces generated by the actomyosin cortex to maintain optimal cell-surface contact area and adhesion on surfaces of various chemical composition and that individual cells migrate with similar speed and contact area on the different surfaces. In contrast, during collective migration, as observed in wound healing and metastasis, the balance between surface forces and protrusive forces is altered. We found that Dictyostelium collective migration dynamics are strongly affected when cells are plated on different surfaces. These results suggest that the presence of cell-cell contacts, which appear as Dictyostelium cells enter development, alter the mechanism cells use to migrate on surfaces of varying composition.
C1 [McCann, Colin P.; Rericha, Erin C.; Losert, Wolfgang] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
[McCann, Colin P.; Rericha, Erin C.; Wang, Chenlu; Parent, Carole A.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Losert, Wolfgang; Parent, Carole A.] Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA.
[Wang, Chenlu] Univ Maryland, Biophys Grad Program, College Pk, MD 20742 USA.
RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM parentc@mail.nih.gov
FU Intramural Research Program of the Center for Cancer Research in the
National Cancer Institute; Burroughs Wellcome Fund; NSF-Physics of
Living Systems Program [PHY07A50371]; NSF-Cyber Physical Systems Grant
[CPS0931508]
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research in the National Cancer Institute. Erin Rericha holds
a Career Award at the Scientific Interface from the Burroughs Wellcome
Fund. WL and ER acknowledge support from the NSF-Physics of Living
Systems Program Grant PHY07A50371. WL and CW also received support from
the NSF-Cyber Physical Systems Grant CPS0931508. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 39
TC 3
Z9 3
U1 2
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 6
PY 2014
VL 9
IS 2
AR e87981
DI 10.1371/journal.pone.0087981
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA1BH
UT WOS:000330830700036
PM 24516575
ER
PT J
AU Wu, T
Schwender, H
Ruczinski, I
Murray, JC
Marazita, ML
Munger, RG
Hetmanski, JB
Parker, MM
Wang, P
Murray, T
Taub, M
Li, S
Redett, RJ
Fallin, MD
Liang, KY
Wu-Chou, YH
Chong, SS
Yeow, V
Ye, XQ
Wang, H
Huang, SZ
Jabs, EW
Shi, B
Wilcox, AJ
Jee, SH
Scott, AF
Beaty, TH
AF Wu, Tao
Schwender, Holger
Ruczinski, Ingo
Murray, Jeffrey C.
Marazita, Mary L.
Munger, Ronald G.
Hetmanski, Jacqueline B.
Parker, Margaret M.
Wang, Ping
Murray, Tanda
Taub, Margaret
Li, Shuai
Redett, Richard J.
Fallin, M. Daniele
Liang, Kung Yee
Wu-Chou, Yah Huei
Chong, Samuel S.
Yeow, Vincent
Ye, Xiaoqian
Wang, Hong
Huang, Shangzhi
Jabs, Ethylin W.
Shi, Bing
Wilcox, Allen J.
Jee, Sun Ha
Scott, Alan F.
Beaty, Terri H.
TI Evidence of Gene-Environment Interaction for Two Genes on Chromosome 4
and Environmental Tobacco Smoke in Controlling the Risk of Nonsyndromic
Cleft Palate
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SYNDROMIC ORAL CLEFTS; SERUM URIC-ACID;
OROFACIAL CLEFTS; CANDIDATE GENES; MATERNAL SMOKING;
CARDIOVASCULAR-DISEASE; CIGARETTE-SMOKING; LIP; POPULATION
AB Nonsyndromic cleft palate (CP) is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS) using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP) achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS) among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester). When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10(-6) Dm8 -> Tm5c form a hard-wired glutamatergic circuit that mediates UV preference by pooling similar to 16 R7 signals for transfer to the lobula, a higher visual center.
C1 [Karuppudurai, Thangavel; Lin, Tzu-Yang; Ting, Chun-Yuan; Melnattur, Krishna V.; Lee, Chi-Hon] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuronal Connect, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
[Pursley, Randall; Pohida, Thomas] NIMH, Signal Proc & Instrumentat Sect, Div Computat Biosci, Ctr Informat Technol,NIH, Bethesda, MD 20892 USA.
[Diao, Fengqiu; White, Benjamin H.] NIMH, Sect Neural Funct, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Macpherson, Lindsey J.; Gallio, Marco] Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA.
[Macpherson, Lindsey J.; Gallio, Marco] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
RP Lee, CH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuronal Connect, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
EM leechih@mail.nih.gov
RI Karuppudurai, Thangavel/C-4831-2014;
OI Gallio, Marco/0000-0003-2132-0639
FU Intramural Research Programs of the National Institutes of Health (NIH);
Eunice Kennedy Shriver National Institute of Child Health and Human
Development [Z01-HD008776]; National Institute of Mental Health
[1ZIA-MH-002800-07]; Center for Information Technology; NIH
[RC1-NS069014, R01-NS076774]
FX We thank Shinya Takemura and Dmitri Chklovskii for communicating results
prior to publication; Tzumin Lee, Kristin Scott, Stephan Sigrist, Aaron
DiAntonio, Gerald Rubin, and Claude Desplan for providing critical
reagents; and Mark Mayer and Alan Hinnebusch for helpful discussion.
This work was supported by the Intramural Research Programs of the
National Institutes of Health (NIH), Eunice Kennedy Shriver National
Institute of Child Health and Human Development (grant Z01-HD008776 to
C.-H. L), National Institute of Mental Health (project 1ZIA-MH-002800-07
to B. H. W.), and Center for Information Technology (to R. P. and T.
P.). L.J.M. and M.G.'s research was supported by NIH grants
(RC1-NS069014 and R01-NS076774) to Charles Zuker.
NR 42
TC 25
Z9 25
U1 0
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD FEB 5
PY 2014
VL 81
IS 3
BP 603
EP 615
DI 10.1016/j.neuron.2013.12.010
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA AA3AO
UT WOS:000330965500014
PM 24507194
ER
PT J
AU Neubert, FX
Mars, RB
Thomas, AG
Sallet, J
Rushworth, MFS
AF Neubert, Franz-Xaver
Mars, Rogier B.
Thomas, Adam G.
Sallet, Jerome
Rushworth, Matthew F. S.
TI Comparison of Human Ventral Frontal Cortex Areas for Cognitive Control
and Language with Areas in Monkey Frontal Cortex
SO NEURON
LA English
DT Article
ID CONNECTIVITY-BASED PARCELLATION; COMPARATIVE CYTOARCHITECTONIC ANALYSIS;
INTRINSIC FUNCTIONAL ARCHITECTURE; TRACTOGRAPHY-BASED PARCELLATION;
INFERIOR PARIETAL LOBULE; PREFRONTAL CORTEX; MACAQUE MONKEY; BROCAS
AREA; SOCIAL COGNITION; PREMOTOR CORTEX
AB Human ventrolateral frontal cortex (vlFC) is identified with cognitive processes such as language and cognitive flexibility. The relationship between it and the vlFC of other primates has therefore been the subject of particular speculation. We used a combination of structural and functional neuroimaging methods to identify key components of human vlFC. We compared how vlFC areas interacted with other brain areas in 25 humans and 25 macaques using the same methods. We identified a core set of 11 vlFC components that interacted in similar ways with similar distributed circuits in both species and, in addition, one distinctively human component in ventrolateral frontal pole. Fundamental differences in interactions with posterior auditory association areas in the two species were also present-these were ubiquitous throughout posterior human vlFC but channeled to different frontal regions in monkeys. Finally, there were some differences in interregional interactions within vlFC in the two species.
C1 [Neubert, Franz-Xaver; Mars, Rogier B.; Sallet, Jerome; Rushworth, Matthew F. S.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England.
[Mars, Rogier B.; Thomas, Adam G.; Rushworth, Matthew F. S.] John Radcliffe Hosp, Oxford Ctr Funct MRI Brain, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England.
[Thomas, Adam G.] NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA.
RP Neubert, FX (reprint author), Univ Oxford, Dept Expt Psychol, 9 South Parks Rd, Oxford OX1 3UD, England.
EM franz-xaver.neubert@psy.ox.ac.uk
OI Thomas, Adam/0000-0002-2850-1419
FU Medical Research Council (United Kingdom) [G0802146]; Gustav Born
Scholarship; Christopher Welch Scholarship
FX This research was supported by Medical Research Council (United Kingdom)
G0802146 (to M. F. S. R. and R. B. M.), a Gustav Born Scholarship (to
F.-X.N.), and a Christopher Welch Scholarship (to F.-X.N.). We thank
Vanessa M. Johnen for helpful comments on an earlier version of the
manuscript.
NR 59
TC 75
Z9 75
U1 4
U2 27
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD FEB 5
PY 2014
VL 81
IS 3
BP 700
EP 713
DI 10.1016/j.neuron.2013.11.012
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA AA3AO
UT WOS:000330965500022
PM 24485097
ER
PT J
AU George, SM
Alfano, CM
Groves, J
Karabulut, Z
Haman, KL
Murphy, BA
Matthews, CE
AF George, Stephanie M.
Alfano, Catherine M.
Groves, Jay
Karabulut, Zafer
Haman, Kirsten L.
Murphy, Barbara A.
Matthews, Charles E.
TI Objectively Measured Sedentary Time Is Related to Quality of Life among
Cancer Survivors
SO PLOS ONE
LA English
DT Article
ID PHYSICAL-ACTIVITY; HEALTH; INTERVENTION; POSTURE; DISEASE; HUMANS;
SF-36; MOVE
AB Purpose: While exercise has been shown to be beneficial in improving health-related quality of life (HRQOL) among cancer survivors, evidence is limited on the independent role of sedentary behavior. We examined how objectively measured sedentary time was associated with HRQOL among long-term cancer survivors.
Methods: This cross-sectional study included 54 cancer survivors, on average 3.4 years postdiagnosis, who were enrolled into an exercise trial designed to improve cognitive function. At baseline, we measured sedentary time and moderate-vigorous intensity physical activity with the ActivPal, cardiorespiratory fitness with treadmill testing, and self-reported HRQOL with an established scale (SF-36). In multivariate models, we regressed HRQOL on sedentary time (percent of waking time spent sitting and lying).
Results: Survivors with higher sedentary time had significantly poorer physical functioning (beta = -0.50, p = 0.028), general health (beta = -0.75, ptrend = 0.004), and physical summary scores (beta = -0.34, p = 0.003). We did not observe associations between sedentary time and role-physical (p = 0.342), bodily-pain (p = 0.117), vitality (p = 0.095), social functioning (p = 0.407), role-emotional (p = 0.509), mental health (p = 0.494), or mental summary scores (p = 0.527).
Conclusion: In this cross-sectional study of cancer survivors, we observed deleterious associations between sedentary time and aspects of physical HRQOL. Future prospective studies of sedentary time and HRQOL are needed to establish temporality and to facilitate the design of effective health promotion interventions for cancer survivors.
C1 [George, Stephanie M.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA.
[Groves, Jay; Karabulut, Zafer] Vanderbilt Univ, Med Ctr, Vanderbilt Dayani Ctr Hlth & Wellness, Nashville, TN USA.
[Haman, Kirsten L.] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA.
[Murphy, Barbara A.] Vanderbilt Univ, Dept Med, Div Hematol Oncol, Nashville, TN USA.
[Matthews, Charles E.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA.
RP George, SM (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA.
EM Stephanie.george@nih.gov
RI matthews, Charles/E-8073-2015
OI matthews, Charles/0000-0001-8037-3103
FU Lance Armstrong Foundation
FX This study was funded by the Lance Armstrong Foundation. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 38
TC 15
Z9 15
U1 0
U2 18
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 5
PY 2014
VL 9
IS 2
AR e87937
DI 10.1371/journal.pone.0087937
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA1AT
UT WOS:000330829200087
PM 24505335
ER
PT J
AU Ma, Y
Chapman, J
Levine, M
Polireddy, K
Drisko, J
Chen, Q
AF Ma, Yan
Chapman, Julia
Levine, Mark
Polireddy, Kishore
Drisko, Jeanne
Chen, Qi
TI High-Dose Parenteral Ascorbate Enhanced Chemosensitivity of Ovarian
Cancer and Reduced Toxicity of Chemotherapy
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID VITAMIN-C PHARMACOKINETICS; TERMINAL HUMAN CANCER; I CLINICAL-TRIAL;
CELL-DEATH; PANCREATIC-CANCER; DNA-DAMAGE; OXIDATIVE STRESS;
PHARMACOLOGICAL CONCENTRATIONS; SUPPLEMENTAL ASCORBATE; SUPPORTIVE
TREATMENT
AB Ascorbate (vitamin C) was an early, unorthodox therapy for cancer, with an outstanding safety profile and anecdotal clinical benefit. Because oral ascorbate was ineffective in two cancer clinical trials, ascorbate was abandoned by conventional oncology but continued to be used in complementary and alternative medicine. Recent studies provide rationale for reexamining ascorbate treatment. Because of marked pharmacokinetic differences, intravenous, but not oral, ascorbate produces millimolar concentrations both in blood and in tissues, killing cancer cells without harming normal tissues. In the interstitial fluid surrounding tumor cells, millimolar concentrations of ascorbate exert local pro-oxidant effects by mediating hydrogen peroxide (H2O2) formation, which kills cancer cells. We investigated downstream mechanisms of ascorbate-induced cell death. Data show that millimolar ascorbate, acting as a pro-oxidant, induced DNA damage and depleted cellular adenosine triphosphate (ATP), activated the ataxia telangiectasia mutated (ATM)/adenosine monophosphate-activated protein kinase (AMPK) pathway, and resulted in mammalian target of rapamycin (mTOR) inhibition and death in ovarian cancer cells. The combination of parenteral ascorbate with the conventional chemotherapeutic agents carboplatin and paclitaxel synergistically inhibited ovarian cancer in mouse models and reduced chemotherapy-associated toxicity in patients with ovarian cancer. On the basis of its potential benefit and minimal toxicity, examination of intravenous ascorbate in combination with standard chemotherapy is justified in larger clinical trials.
C1 [Ma, Yan; Polireddy, Kishore; Chen, Qi] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA.
[Ma, Yan; Polireddy, Kishore; Drisko, Jeanne; Chen, Qi] Univ Kansas, Med Ctr, KU Integrat Med, Kansas City, KS 66160 USA.
[Chapman, Julia] Univ Kansas, Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Kansas City, KS 66160 USA.
[Levine, Mark] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD 20892 USA.
RP Chen, Q (reprint author), Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA.
EM jdrisko@kumc.edu; qchen@kumc.edu
RI Bollu, Lakshmi/O-4992-2015; Chen, Qi/D-8278-2015
OI Bollu, Lakshmi/0000-0001-9596-6251; Chen, Qi/0000-0002-7173-8411
FU Gateway for Cancer Research Foundation; University of Kansas Endowment
by the L. Charles Hilton Family Foundation; University of Kansas
Research Institute; Intramural Research Program, National Institute of
Diabetes and Digestive and Kidney Diseases, NIH
FX Funding: This work was financially supported by Gateway for Cancer
Research Foundation (formerly Cancer Treatment Research Foundation,
Schaumburg, IL), a grant from the University of Kansas Endowment
provided by the L. Charles Hilton Family Foundation, a bridging grant
from the University of Kansas Research Institute, and the Intramural
Research Program, National Institute of Diabetes and Digestive and
Kidney Diseases, NIH.
NR 57
TC 42
Z9 43
U1 2
U2 24
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD FEB 5
PY 2014
VL 6
IS 222
AR 222ra18
DI 10.1126/scitranslmed.3007154
PG 10
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AA4UF
UT WOS:000331091100008
PM 24500406
ER
PT J
AU James, PA
Oparil, S
Carter, BL
Cushman, WC
Dennison-Himmelfarb, C
Handler, J
Lackland, DT
LeFevre, ML
MacKenzie, TD
Ogedegbe, O
Smith, SC
Svetkey, LP
Taler, SJ
Townsend, RR
Wright, JT
Narva, AS
Ortiz, E
AF James, Paul A.
Oparil, Suzanne
Carter, Barry L.
Cushman, William C.
Dennison-Himmelfarb, Cheryl
Handler, Joel
Lackland, Daniel T.
LeFevre, Michael L.
MacKenzie, Thomas D.
Ogedegbe, Olugbenga
Smith, Sidney C., Jr.
Svetkey, Laura P.
Taler, Sandra J.
Townsend, Raymond R.
Wright, Jackson T., Jr.
Narva, Andrew S.
Ortiz, Eduardo
TI 2014 Evidence-Based Guideline for the Management of High Blood Pressure
in Adults Report From the Panel Members Appointed to the Eighth Joint
National Committee (JNC 8)
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID ISOLATED SYSTOLIC HYPERTENSION; LIPID-LOWERING TREATMENT; HEART-ATTACK
TRIAL; CONVERTING ENZYME-INHIBITOR; RANDOMIZED CONTROLLED-TRIAL; TYPE-2
DIABETES-MELLITUS; CALCIUM-CHANNEL BLOCKER; CHRONIC RENAL-DISEASE;
HIGH-RISK; OLDER PATIENTS
AB Hypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want guidance on hypertension management using the best scientific evidence. This report takes a rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults. Evidence was drawn from randomized controlled trials, which represent the gold standard for determining efficacy and effectiveness. Evidence quality and recommendations were graded based on their effect on important outcomes.
There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg; however, there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion. The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years. There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes.
Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.
C1 [James, Paul A.; Carter, Barry L.] Univ Iowa, Iowa City, IA 52242 USA.
[Oparil, Suzanne] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA.
[Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA.
[Cushman, William C.] Univ Tennessee, Memphis, TN USA.
[Dennison-Himmelfarb, Cheryl] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA.
[Handler, Joel] Kaiser Permanente, Anaheim, CA USA.
[Lackland, Daniel T.] Med Univ S Carolina, Charleston, SC USA.
[LeFevre, Michael L.] Univ Missouri, Columbia, MO 65211 USA.
[MacKenzie, Thomas D.] Denver Hlth & Hosp Author, Denver, CO USA.
[MacKenzie, Thomas D.] Univ Colorado, Sch Med, Denver, CO USA.
[Ogedegbe, Olugbenga] NYU, Sch Med, New York, NY USA.
[Smith, Sidney C., Jr.] Univ N Carolina, Chapel Hill, NC USA.
[Svetkey, Laura P.] Duke Univ, Durham, NC USA.
[Taler, Sandra J.] Mayo Clin, Coll Med, Rochester, MN USA.
[Townsend, Raymond R.] Univ Penn, Philadelphia, PA 19104 USA.
[Wright, Jackson T., Jr.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Narva, Andrew S.] NIDDK, Bethesda, MD 20892 USA.
[Ortiz, Eduardo] NHLBI, Bethesda, MD 20892 USA.
RP James, PA (reprint author), Univ Iowa, 200 Hawkins Dr,01286-D PFP, Iowa City, IA 52242 USA.
EM paul-james@uiowa.edu
FU National Heart, Lung, and Blood Institute (NHLBI)
FX The evidence review for this project was funded by the National Heart,
Lung, and Blood Institute (NHLBI).
NR 45
TC 1872
Z9 2018
U1 55
U2 265
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD FEB 5
PY 2014
VL 311
IS 5
BP 507
EP 520
DI 10.1001/jama.2013.284427
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA 302GF
UT WOS:000330589800024
PM 24352797
ER
PT J
AU Coker, LH
Espeland, MA
Hogan, PE
Resnick, SM
Bryan, RN
Robinson, JG
Goveas, JS
Davatzikos, C
Kuller, LH
Williamson, JD
Bushnell, CD
Shumaker, SA
AF Coker, Laura H.
Espeland, Mark A.
Hogan, Patricia E.
Resnick, Susan M.
Bryan, R. Nick
Robinson, Jennifer G.
Goveas, Joseph S.
Davatzikos, Christos
Kuller, Lewis H.
Williamson, Jeff D.
Bushnell, Cheryl D.
Shumaker, Sally A.
CA WHIMS-MRI Study Grp
TI Change in brain and lesion volumes after CEE therapies The WHIMS-MRI
studies
SO NEUROLOGY
LA English
DT Article
ID WHITE-MATTER LESIONS; POSTMENOPAUSAL HORMONE-THERAPY; RANDOMIZED
CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; MITOCHONDRIAL BIOENERGETICS;
MAGNETIC-RESONANCE; ALZHEIMERS-DISEASE; COGNITIVE FUNCTION; EQUINE
ESTROGEN; WOMEN
AB Objectives:To determine whether smaller brain volumes in older women who had completed Women's Health Initiative (WHI)-assigned conjugated equine estrogen-based hormone therapy (HT), reported by WHI Memory Study (WHIMS)-MRI, correspond to a continuing increased rate of atrophy an average of 6.1 to 7.7 years later in WHIMS-MRI2.Methods:A total of 1,230 WHI participants were contacted: 797 (64.8%) consented, and 729 (59%) were rescanned an average of 4.7 years after the initial MRI scan. Mean annual rates of change in total brain volume, the primary outcome, and rates of change in ischemic lesion volumes, the secondary outcome, were compared between treatment groups using mixed-effect models with adjustment for trial, clinical site, age, intracranial volumes, and time between MRI measures.Results:Total brain volume decreased an average of 3.22 cm(3)/y in the active arm and 3.07 cm(3)/y in the placebo arm (p = 0.53). Total ischemic lesion volumes increased in both arms at a rate of 0.12 cm(3)/y (p = 0.88).Conclusions:Conjugated equine estrogen-based postmenopausal HT, previously assigned at WHI baseline, did not affect rates of decline in brain volumes or increases in brain lesion volumes during the 4.7 years between the initial and follow-up WHIMS-MRI studies. Smaller frontal lobe volumes were observed as persistent group differences among women assigned to active HT compared with placebo. Women with a history of cardiovascular disease treated with active HT, compared with placebo, had higher rates of accumulation in white matter lesion volume and total brain lesion volume. Further study may elucidate mechanisms that explain these findings.
C1 [Coker, Laura H.; Espeland, Mark A.; Hogan, Patricia E.; Shumaker, Sally A.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA.
[Williamson, Jeff D.] Wake Forest Sch Med, Dept Internal Med & Geriatr, Winston Salem, NC USA.
[Bushnell, Cheryl D.] Wake Forest Sch Med, Dept Neurol, Winston Salem, NC USA.
[Resnick, Susan M.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Bryan, R. Nick; Davatzikos, Christos] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
[Robinson, Jennifer G.] Univ Iowa, Dept Internal Med & Epidemiol, Iowa City, IA USA.
[Goveas, Joseph S.] Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA.
[Kuller, Lewis H.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
RP Coker, LH (reprint author), Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA.
EM lcoker@wakehealth.edu
FU National Heart, Lung, and Blood Institute, NIH
FX Supported by the National Heart, Lung, and Blood Institute, NIH.
NR 29
TC 11
Z9 11
U1 0
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 4
PY 2014
VL 82
IS 5
BP 427
EP 434
DI 10.1212/WNL.0000000000000079
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH9WA
UT WOS:000336494600014
PM 24384646
ER
PT J
AU Bedford, T
Suchard, MA
Lemey, P
Dudas, G
Gregory, V
Hay, AJ
McCauley, JW
Russell, CA
Smith, DJ
Rambaut, A
AF Bedford, Trevor
Suchard, Marc A.
Lemey, Philippe
Dudas, Gytis
Gregory, Victoria
Hay, Alan J.
McCauley, John W.
Russell, Colin A.
Smith, Derek J.
Rambaut, Andrew
TI Integrating influenza antigenic dynamics with molecular evolution
SO ELIFE
LA English
DT Article
ID A H1N1 VIRUSES; B VIRUSES; EPIDEMIC INFLUENZA; AMINO-ACID; HEMAGGLUTININ
GENE; SEQUENCE-ANALYSIS; GENOMIC ANALYSES; UNITED-KINGDOM; DRIFT;
VARIANTS
AB Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. Antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (HI) assay. Here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phylogeny. Using HI data from influenza lineages A/H3N2, A/H1N1, B/Victoria and B/Yamagata, we determine patterns of antigenic drift across viral lineages, showing that A/H3N2 evolves faster and in a more punctuated fashion than other influenza lineages. We also show that year-to-year antigenic drift appears to drive incidence patterns within each influenza lineage. This work makes possible substantial future advances in investigating the dynamics of influenza and other antigenically-variable pathogens by providing a model that intimately combines molecular and antigenic evolution.
C1 [Bedford, Trevor; Dudas, Gytis; Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland.
[Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA.
[Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
[Suchard, Marc A.] Univ Calif Los Angeles, UCLA Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA.
[Lemey, Philippe] Katholieke Univ Leuven, Rega Inst, Dept Microbiol & Immunol, Louvain, Belgium.
[Gregory, Victoria; Hay, Alan J.; McCauley, John W.] Natl Inst Med Res, MRC, Div Virol, London NW7 1AA, England.
[Russell, Colin A.; Smith, Derek J.] Univ Cambridge, WHO Collaborating Ctr Modeling Evolut & Control E, Cambridge, England.
[Russell, Colin A.] Univ Cambridge, Dept Vet Med, Cambridge, England.
[Smith, Derek J.] Univ Cambridge, Dept Zool, Ctr Pathogen Evolut, Cambridge, England.
[Smith, Derek J.] Erasmus MC, Dept Virol, Rotterdam, Netherlands.
[Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Rambaut, Andrew] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland.
RP Bedford, T (reprint author), Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland.
EM tbedford@fhcrc.org
OI Bedford, Trevor/0000-0002-4039-5794; Russell, Colin/0000-0002-2113-162X;
Rambaut, Andrew/0000-0003-4337-3707; Dudas, Gytis/0000-0002-0227-4158
FU Royal Society; National Institutes of Health [R01 HG006139, R01
AI107034, DP1-OD000490-01, HHSN266200700010C]; National Science
Foundation [DMS126153, IIS1251151, EF-0423641]; European Commission
[278433-PREDEMICS, 260864, 223498-EMPERIE, 278976-ANTIGONE]; Medical
Research Council [U117512723]; Wellcome Trust [092807, 087982AIA]; Human
Frontier Science Program [P0050/2008]
FX Royal Society Newton International Fellowship Trevor Bedford; National
Institutes of Health R01 HG006139 Marc A Suchard; National Institutes of
Health R01 AI107034 Marc A Suchard; National Science Foundation
DMS126153 Marc A Suchard; National Science Foundation IIS1251151 Marc A
Suchard; European Commission 278433-PREDEMICS Marc A Suchard, Philippe
Lemey, Andrew Rambaut; European Commission 260864 Marc A Suchard,
Philippe Lemey, Andrew Rambaut; National Science Foundation EF-0423641
Marc A Suchard, Philippe Lemey, Andrew Rambaut; Medical Research Council
U117512723 Victoria Gregory, Alan J Hay, John W McCauley; Wellcome Trust
092807 Andrew Rambaut; European Commission 223498-EMPERIE Colin A
Russell, Derek J Smith; European Commission 278976-ANTIGONE Colin A
Russell, Derek J Smith; Human Frontier Science Program P0050/2008 Colin
A Russell, Derek J Smith; Wellcome Trust 087982AIA Colin A Russell,
Derek J Smith; National Institutes of Health DP1-OD000490-01 Colin A
Russell, Derek J Smith; National Institutes of Health HHSN266200700010C
Colin A Russell, Derek J Smith; Royal Society University Research
Fellowship Colin A Russell
NR 78
TC 64
Z9 67
U1 5
U2 20
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD FEB 4
PY 2014
VL 3
AR e01914
DI 10.7554/eLife.01914
PG 26
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA AA7RF
UT WOS:000331293900006
PM 24497547
ER
PT J
AU MacKinnon, AL
Paavilainen, VO
Sharma, A
Hegde, RS
Taunton, J
AF MacKinnon, Andrew L.
Paavilainen, Ville O.
Sharma, Ajay
Hegde, Ramanujan S.
Taunton, Jack
TI An allosteric Sec61 inhibitor traps nascent transmembrane helices at the
lateral gate
SO ELIFE
LA English
DT Article
ID MEMBRANE-PROTEIN INTEGRATION; SIGNAL SEQUENCE RECOGNITION; CELL-ADHESION
MOLECULE-1; ENDOPLASMIC-RETICULUM; COTRANSLATIONAL TRANSLOCATION; ER
MEMBRANE; CONDUCTING CHANNEL; COMPLEX; INSERTION; TRANSPORT
AB Membrane protein biogenesis requires the coordinated movement of hydrophobic transmembrane domains (TMD) from the cytosolic vestibule of the Sec61 channel into the lipid bilayer. Molecular insight into TMD integration has been hampered by the difficulty of characterizing intermediates during this intrinsically dynamic process. In this study, we show that cotransin, a substrate-selective Sec61 inhibitor, traps nascent TMDs in the cytosolic vestibule, permitting detailed interrogation of an early pre-integration intermediate. Site-specific crosslinking revealed the pre-integrated TMD docked to Sec61 near the cytosolic tip of the lateral gate. Escape from cotransin-arrest depends not only on cotransin concentration, but also on the biophysical properties of the TMD. Genetic selection of cotransin-resistant cancer cells uncovered multiple mutations clustered near the lumenal plug of Sec61 alpha, thus revealing cotransin's likely site of action. Our results suggest that TMD/lateral gate interactions facilitate TMD transfer into the membrane, a process that is allosterically modulated by cotransin binding to the plug.
C1 [MacKinnon, Andrew L.; Paavilainen, Ville O.; Taunton, Jack] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
[Sharma, Ajay; Hegde, Ramanujan S.] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Taunton, Jack] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA USA.
RP Taunton, J (reprint author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
EM jack.taunton@ucsf.edu
OI Paavilainen, Ville/0000-0002-3160-7767; Hegde,
Ramanujan/0000-0001-8338-852X
FU National Institutes of Health [GM081644]; Medical Research Council;
Academy of Finland; Sigrid Juselius Foundation
FX National Institutes of Health GM081644 Ramanujan S Hegde, Jack Taunton;
Medical Research Council Ramanujan S Hegde; The Academy of Finland Ville
O Paavilainen; Sigrid Juselius Foundation Ville O Paavilainen
NR 51
TC 17
Z9 17
U1 1
U2 8
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD FEB 4
PY 2014
VL 3
AR e01483
DI 10.7554/eLife.01483
PG 23
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA AA7RF
UT WOS:000331293900003
PM 24497544
ER
PT J
AU Pratt, CA
Arteaga, S
Loria, C
AF Pratt, Charlotte A.
Arteaga, Sonia
Loria, Catherine
TI Forging a Future of Better Cardiovascular Health Addressing Childhood
Obesity
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT News Item
DE cardiovascular health; childhood obesity; NHLBIQ
ID ASSOCIATION; CHILDREN
C1 [Pratt, Charlotte A.; Arteaga, Sonia; Loria, Catherine] NHLBI, Clin Applicat & Prevent Branch, Prevent & Populat Sci Program, NIH, Bethesda, MD 20892 USA.
RP Pratt, CA (reprint author), NHLBI, Prevent & Populat Sci Program, Div Cardiovasc Sci, 6701 Rockledge Dr,Suite 10118, Bethesda, MD 20892 USA.
EM prattc@nhlbi.nih.gov
NR 9
TC 2
Z9 2
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 4
PY 2014
VL 63
IS 4
BP 369
EP 371
DI 10.1016/j.jacc.2013.07.088
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 297AM
UT WOS:000330227200013
PM 24076288
ER
PT J
AU Zolla-Pazner, S
deCamp, A
Gilbert, PB
Williams, C
Yates, NL
Williams, WT
Howington, R
Fong, YY
Morris, DE
Soderberg, KA
Irene, C
Reichman, C
Pinter, A
Parks, R
Pitisuttithum, P
Kaewkungwal, J
Rerks-Ngarm, S
Nitayaphan, S
Andrews, C
O'Connell, RJ
Yang, ZY
Nabel, GJ
Kim, JH
Michael, NL
Montefiori, DC
Liao, HX
Haynes, BF
Tomaras, GD
AF Zolla-Pazner, Susan
deCamp, Allan
Gilbert, Peter B.
Williams, Constance
Yates, Nicole L.
Williams, William T.
Howington, Robert
Fong, Youyi
Morris, Daryl E.
Soderberg, Kelly A.
Irene, Carmela
Reichman, Charles
Pinter, Abraham
Parks, Robert
Pitisuttithum, Punnee
Kaewkungwal, Jaranit
Rerks-Ngarm, Supachai
Nitayaphan, Sorachai
Andrews, Charla
O'Connell, Robert J.
Yang, Zhi-yong
Nabel, Gary J.
Kim, Jerome H.
Michael, Nelson L.
Montefiori, David C.
Liao, Hua-Xin
Haynes, Barton F.
Tomaras, Georgia D.
TI Vaccine-Induced IgG Antibodies to V1V2 Regions of Multiple HIV-1
Subtypes Correlate with Decreased Risk of HIV-1 Infection
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; B-CELL
RESPONSES; HIV-1-INFECTED INDIVIDUALS; CROSS-REACTIVITY; V1/V2 DOMAIN;
ENVELOPE; NEUTRALIZATION; GP120; SEQUENCE
AB In the RV144 HIV-1 vaccine efficacy trial, IgG antibody (Ab) binding levels to variable regions 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 were an inverse correlate of risk of HIV-1 infection. To determine if V1V2-specific Abs cross-react with V1V2 from different HIV-1 subtypes, if the nature of the V1V2 antigen used to asses cross-reactivity influenced infection risk, and to identify immune assays for upcoming HIV-1 vaccine efficacy trials, new V1V2-scaffold antigens were designed and tested. Protein scaffold antigens carrying the V1V2 regions from HIV-1 subtypes A, B, C, D or CRF01_AE were assayed in pilot studies, and six were selected to assess cross-reactive Abs in the plasma from the original RV144 case-control cohort (41 infected vaccinees, 205 frequency-matched uninfected vaccinees, and 40 placebo recipients) using ELISA and a binding Ab multiplex assay. IgG levels to these antigens were assessed as correlates of risk in vaccine recipients using weighted logistic regression models. Levels of Abs reactive with subtype A, B, C and CRF01_AE V1V2-scaffold antigens were all significant inverse correlates of risk (p-values of 0.0008-0.05; estimated odds ratios of 0.53-0.68 per 1 standard deviation increase). Thus, levels of vaccine-induced IgG Abs recognizing V1V2 regions from multiple HIV-1 subtypes, and presented on different scaffolds, constitute inverse correlates of risk for HIV-1 infection in the RV144 vaccine trial. The V1V2 antigens provide a link between RV144 and upcoming HIV-1 vaccine trials, and identify reagents and methods for evaluating V1V2 Abs as possible correlates of protection against HIV-1 infection.
C1 [Zolla-Pazner, Susan] New York Harbor Healthcare Syst, Dept Vet Affairs, New York, NY 10010 USA.
[Zolla-Pazner, Susan; Williams, Constance] NYU, Sch Med, New York, NY USA.
[deCamp, Allan; Gilbert, Peter B.; Fong, Youyi; Morris, Daryl E.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Yates, Nicole L.; Williams, William T.; Howington, Robert; Soderberg, Kelly A.; Parks, Robert; Montefiori, David C.; Liao, Hua-Xin; Haynes, Barton F.; Tomaras, Georgia D.] Duke Univ, Durham, NC USA.
[Irene, Carmela; Reichman, Charles; Pinter, Abraham] Univ Med & Dent New Jersey, Publ Hlth Res Inst, Newark, NJ 07103 USA.
[Pitisuttithum, Punnee; Kaewkungwal, Jaranit] Fac Trop Med, Mahidol, Thailand.
[Rerks-Ngarm, Supachai] Minist Publ Hlth, Bangkok, Thailand.
[Nitayaphan, Sorachai] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand.
[Andrews, Charla; O'Connell, Robert J.; Kim, Jerome H.; Michael, Nelson L.] Walter Reed Army Inst Res, Mil HIV Res Program, Silver Spring, MD USA.
[Yang, Zhi-yong; Nabel, Gary J.] NIAID, Virol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Zolla-Pazner, S (reprint author), New York Harbor Healthcare Syst, Dept Vet Affairs, New York, NY 10010 USA.
EM zollas01@med.nyu.edu
RI Tomaras, Georgia/J-5041-2016
FU National Institutes of Health [P01 AI100151, R01 HL59725, P01 AI64518];
Bill and Melinda Gates Foundation [1040758, 3830913]; Military HIV
Research Program; Department of Veterans Affairs, Veterans Health
Administration, Office of Research and Development; U.S. Army Medical
Research and Material Command (USAMRMC) [Y1-AI-2642-12]; National
Institutes of Allergy and Infectious Diseases [Y1-AI-2642-12]; Henry M.
Jackson Foundation for the Advancement of Military Medicine, Inc.
[W81XWH-07-2-0067]; U.S. Department of Defense [W81XWH-07-2-0067]
FX Supported in part by grant funds from the National Institutes of Health:
P01 AI100151 (SZP), R01 HL59725 (SZP), P01 AI64518 (Duke Center for AIDS
Research); from the Bill and Melinda Gates Foundation: 1040758 (BFH),
and 3830913 (DCM); from the Military HIV Research Program, and research
funds from the Department of Veterans Affairs, Veterans Health
Administration, Office of Research and Development. The work was also
supported in part by an Interagency Agreement Y1-AI-2642-12 between the
U.S. Army Medical Research and Material Command (USAMRMC) and the
National Institutes of Allergy and Infectious Diseases and by a
cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson
Foundation for the Advancement of Military Medicine, Inc., and the U.S.
Department of Defense. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 31
TC 83
Z9 84
U1 2
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 4
PY 2014
VL 9
IS 2
AR e87572
DI 10.1371/journal.pone.0087572
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 302VA
UT WOS:000330631800045
PM 24504509
ER
PT J
AU Berezhkovskii, AM
Dagdug, L
Lizunov, VA
Zimmerberg, J
Bezrukov, SM
AF Berezhkovskii, Alexander M.
Dagdug, Leonardo
Lizunov, Vladimir A.
Zimmerberg, Joshua
Bezrukov, Sergey M.
TI Trapping by Clusters of Channels, Receptors, and Transporters:
Quantitative Description
SO BIOPHYSICAL JOURNAL
LA English
DT Review
ID 1ST PASSAGE TIME; LIGAND-BINDING; SPHINGOLIPID DOMAINS; ASYMPTOTIC
ANALYSIS; PLASMA-MEMBRANES; RATE CONSTANTS; CELL-SURFACE; DIFFUSION;
PROTEIN; HOMOGENIZATION
AB Various membrane functional units such as receptors, transporters, and channels, whose action necessarily involves capturing diffusing molecules, are often organized into multimeric complexes forming clusters on the cell and organelle membranes. These functional units themselves are usually oligomers of several integral proteins, which have their own symmetry. Depending on the symmetry, they form clusters on different packing lattices. Moreover, local membrane inhomogeneities, e.g., the so-called membrane domains, rafts, stalks, etc., lead to different patterns even within the structures on the same packing lattice. Units in the cluster compete for diffusing molecules and screen each other. Here we propose a general approach that allows one to quantify the screening effects. The approach is used to derive simple approximate formulas giving the trapping rates of diffusing molecules by clusters of absorbers on lattices of different packing symmetries. The obtained results describe smooth variation of the trapping rate from the sum of the rates of individual absorbers forming the cluster to the effective collective rate. The latter shows how the trapping efficiency of an individual absorber decreases as the number of absorbers in the cluster increases and/or the inter-absorber distance decreases. Numerical tests demonstrate good agreement between the rates predicted by the theory and obtained from Brownian dynamics simulations for clusters of different shapes and sizes.
C1 [Berezhkovskii, Alexander M.; Dagdug, Leonardo; Lizunov, Vladimir A.; Zimmerberg, Joshua; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Bethesda, MD 20892 USA.
[Berezhkovskii, Alexander M.; Dagdug, Leonardo] NIH, Ctr Informat Technol, Div Computat Biosci, Math & Stat Comp Lab, Bethesda, MD 20892 USA.
[Dagdug, Leonardo] Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Iztapalapa, Mexico.
RP Bezrukov, SM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Bethesda, MD 20892 USA.
EM bezrukos@mail.nih.gov
FU Consejo Nacional de Ciencia y Tecnologia [176452]; National Institutes
of Health, Center for Information Technology; Eunice Kennedy Shriver
National Institute of Child Health and Human Development
FX L.D. is grateful to the Consejo Nacional de Ciencia y Tecnologia for
partial support by grant No. 176452. This study was supported by the
Intramural Research Program of the National Institutes of Health, Center
for Information Technology and the Eunice Kennedy Shriver National
Institute of Child Health and Human Development.
NR 34
TC 1
Z9 1
U1 0
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 4
PY 2014
VL 106
IS 3
BP 500
EP 509
DI 10.1016/j.bpj.2013.12.015
PG 10
WC Biophysics
SC Biophysics
GA 304CV
UT WOS:000330724800003
PM 24507591
ER
PT J
AU Gurnev, PA
Yap, TL
Pfefferkorn, CM
Rostovtseva, TK
Berezhkovskii, AM
Lee, JC
Parsegian, VA
Bezrukov, SM
AF Gurnev, Philip A.
Yap, Thai Leong
Pfefferkorn, Candace M.
Rostovtseva, Tatiana K.
Berezhkovskii, Alexander M.
Lee, Jennifer C.
Parsegian, V. Adrian
Bezrukov, Sergey M.
TI Alpha-Synuclein Lipid-Dependent Membrane Binding and Translocation
through the alpha-Hemolysin Channel
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID PROTEIN TRANSLOCATION; PARKINSONS-DISEASE; ANTHRAX TOXIN; POLYNUCLEOTIDE
MOLECULES; NANOPORE ANALYSIS; LEWY BODIES; PORE; HELIX; TRANSPORT;
PEPTIDES
AB Gauging the interactions of a natively unfolded Parkinson disease-related protein, alpha-synuclein (alpha-syn) with membranes and its pathways between and within cells is important for understanding its pathogenesis. Here, to address these questions, we use a robust beta-barrel channel, alpha-hemolysin, reconstituted into planar lipid bilayers. Transient, similar to 95% blockage of the channel current by alpha-syn was observed when 1), alpha-syn was added from the membrane side where the shorter (stem) part of the channel is exposed; and 2), the applied potential was lower on the side of alpha-syn addition. While the on- rate of alpha-syn binding to the channel strongly increased with the applied field, the off-rate displayed a turnover behavior. Statistical analysis suggests that at voltages >50 mV, a significant fraction of the alpha-syn molecules bound to the channel undergoes subsequent translocation. The observed on- rate varied by > 100 times depending on the bilayer lipid composition. Removal of the last 25 amino acids from the highly negatively charged C-terminal of alpha-syn resulted in a significant decrease in the binding rates. Taken together, these results demonstrate that beta-barrel channels may serve as sensitive probes of alpha-syn interactions with membranes as well as model systems for studies of channel-assisted protein transport.
C1 [Gurnev, Philip A.; Parsegian, V. Adrian] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA.
[Gurnev, Philip A.; Rostovtseva, Tatiana K.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Transport, Program Phys Biol, Bethesda, MD USA.
[Yap, Thai Leong; Pfefferkorn, Candace M.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, Biochem & Biophys Ctr, Bethesda, MD 20892 USA.
[Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Gurnev, PA (reprint author), Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA.
EM gurnev@physics.umass.edu
RI Lee, Jennifer/E-9658-2015
OI Lee, Jennifer/0000-0003-0506-8349
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; National Heart, Lung,
and Blood Institute; Center for Information Technology; National
Institutes of Health; National Science Foundation EAGER [1249199]
FX The work was supported by Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Heart, Lung, and Blood Institute, and Center for
Information Technology, National Institutes of Health, and by National
Science Foundation EAGER award No. 1249199.
NR 68
TC 9
Z9 9
U1 0
U2 21
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 4
PY 2014
VL 106
IS 3
BP 556
EP 565
DI 10.1016/j.bpj.2013.12.028
PG 10
WC Biophysics
SC Biophysics
GA 304CV
UT WOS:000330724800008
PM 24507596
ER
PT J
AU Watts, M
Sherman, A
AF Watts, Margaret
Sherman, Arthur
TI Modeling the Pancreatic alpha-Cell: Dual Mechanisms of Glucose
Suppression of Glucagon Secretion
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID SENSITIVE K+ CHANNEL; BETA-CELLS; HUMAN ISLETS; DELTA-CELLS;
POSTPRANDIAL HYPERGLYCEMIA; ENDOPLASMIC-RETICULUM; ELECTRICAL-ACTIVITY;
ENDOCRINE PANCREAS; IDENTIFIED ALPHA; INTACT ISLETS
AB The mechanism by which glucose induces insulin secretion in beta-cells is fairly well understood. Despite years of research, however, the mechanism of glucagon secretion in alpha-cells is still not well established. It has been proposed that glucose regulates glucagon secretion by decreasing the conductance of either outward ATP-dependent potassium channels (K(ATP)) or an inward store-operated current (SOC). We have developed a mathematical model based on mouse data to test these hypotheses and found that both mechanisms are possible. Glucose metabolism closes K(ATP) channels, which depolarizes the cell but paradoxically reduces calcium influx by inactivating voltage-dependent calcium and sodium channels and decreases secretion. Glucose metabolism also activates SERCA pumps, which fills the endoplasmic reticulum and hyperpolarizes the cells by reducing the inward current through SOC channels and again suppresses glucagon secretion. We find further that the two mechanisms can combine to account for the nonmonotonic dependence of secretion on glucose observed in some studies, an effect that cannot be obtained with either mechanism alone.
C1 [Watts, Margaret; Sherman, Arthur] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RP Sherman, A (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
EM artiesherman@gmail.com
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, Bethesda, MD
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, Bethesda, MD.
NR 58
TC 12
Z9 12
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 4
PY 2014
VL 106
IS 3
BP 741
EP 751
DI 10.1016/j.bpj.2013.11.4504
PG 11
WC Biophysics
SC Biophysics
GA 304CV
UT WOS:000330724800027
PM 24507615
ER
PT J
AU Berezhkovskii, AM
Shvartsman, SY
AF Berezhkovskii, Alexander M.
Shvartsman, Stanislav Y.
TI On the GFP-Based Analysis of Dynamic Concentration Profiles
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID MORPHOGEN GRADIENT; FLUORESCENCE; SYSTEM
AB Studies with GFP-tagged proteins can be used to investigate the dynamics of concentration profiles of regulatory proteins in cells and tissues. Analysis of these experiments must account for the finite rate with which the GFP-tagged proteins mature to the fluorescent state. Toward this end, we present an analytical framework that provides an explicit connection between the apparent kinetics of concentration gradients and the rates of GFP maturation.
C1 [Berezhkovskii, Alexander M.] NIH, Ctr Informat Technol, Div Computat Biosci, Math & Stat Comp Lab, Bethesda, MD 20892 USA.
[Shvartsman, Stanislav Y.] Princeton Univ, Dept Chem & Biol Engn, Princeton, NJ 08544 USA.
[Shvartsman, Stanislav Y.] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
RP Shvartsman, SY (reprint author), Princeton Univ, Dept Chem & Biol Engn, Princeton, NJ 08544 USA.
EM stas@princeton.edu
FU National Institute of General Medical Sciences [R01BM086537]
FX This work was supported by grant R01BM086537 from the National Institute
of General Medical Sciences.
NR 15
TC 1
Z9 1
U1 5
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 4
PY 2014
VL 106
IS 3
BP L13
EP L15
DI 10.1016/j.bpj.2013.12.007
PG 3
WC Biophysics
SC Biophysics
GA 304CV
UT WOS:000330724800001
PM 24507618
ER
PT J
AU Longo, VD
Mattson, MP
AF Longo, Valter D.
Mattson, Mark P.
TI Fasting: Molecular Mechanisms and Clinical Applications
SO CELL METABOLISM
LA English
DT Review
ID AMYOTROPHIC-LATERAL-SCLEROSIS; LIFE-SPAN EXTENSION; I IGF-I; DIETARY
RESTRICTION; CALORIE RESTRICTION; INSULIN-RESISTANCE; BODY-COMPOSITION;
ENERGY-INTAKE; CAENORHABDITIS-ELEGANS; SUPEROXIDE-DISMUTASE
AB Fasting has been practiced for millennia, but, only recently, studies have shed light on its role in adaptive cellular responses that reduce oxidative damage and inflammation, optimize energy metabolism, and bolster cellular protection. In lower eukaryotes, chronic fasting extends longevity, in part, by reprogramming metabolic and stress resistance pathways. In rodents intermittent or periodic fasting protects against diabetes, cancers, heart disease, and neurodegeneration, while in humans it helps reduce obesity, hypertension, asthma, and rheumatoid arthritis. Thus, fasting has the potential to delay aging and help prevent and treat diseases while minimizing the side effects caused by chronic dietary interventions.
C1 [Longo, Valter D.] Univ So Calif, Longev Inst, Davis Sch Gerontol, Los Angeles, CA 90089 USA.
[Mattson, Mark P.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Longo, VD (reprint author), Univ So Calif, Longev Inst, Davis Sch Gerontol, Los Angeles, CA 90089 USA.
EM vlongo@usc.edu; mark.mattson@nih.gov
FU National Institute on Aging; Glenn Foundation for Medical Research;
NIH/NIA [AG20642, AG025135, AG034906]
FX We thank Min Wei for all the assistance with the preparation of the
manuscript. We thank Yvon Le Maho for providing valuable information
about fasting and a picture of penguins. We thank Matt Kaeberlein and
Matthew Piper for panels for Figure 1. We thank William Mair for helpful
discussions on fasting in Drosophila and thank Jay Mitchell for helpful
comments on the manuscript. This work was supported, in part, by the
Intramural Research Program of the National Institute on Aging; by the
Glenn Foundation for Medical Research; and by the NIH/NIA grants
AG20642, AG025135, and AG034906 to V.D.L.
NR 103
TC 110
Z9 112
U1 25
U2 137
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 4
PY 2014
VL 19
IS 2
BP 181
EP 192
DI 10.1016/j.cmet.2013.12.008
PG 12
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 304CE
UT WOS:000330722600005
PM 24440038
ER
PT J
AU Lee, P
Linderman, JD
Smith, S
Brychta, RJ
Wang, J
Idelson, C
Perron, RM
Werner, CD
Phan, GQ
Kammula, US
Kebebew, E
Pacak, K
Chen, KY
Celi, FS
AF Lee, Paul
Linderman, Joyce D.
Smith, Sheila
Brychta, Robert J.
Wang, Juan
Idelson, Christopher
Perron, Rachel M.
Werner, Charlotte D.
Phan, Giao Q.
Kammula, Udai S.
Kebebew, Electron
Pacak, Karel
Chen, Kong Y.
Celi, Francesco S.
TI Irisin and FGF21 Are Cold-Induced Endocrine Activators of Brown Fat
Function in Humans
SO CELL METABOLISM
LA English
DT Article
ID GROWTH-FACTOR 21; ADIPOSE-TISSUE; ADULT HUMANS; INDUCED THERMOGENESIS;
HEALTHY-ADULTS; EXERCISE; TEMPERATURE; ADIPOCYTES; EXPRESSION; EXPOSURE
AB Rediscovery of cold-activated brown adipose tissue (BAT) in humans has boosted research interest in identifying BAT activators for metabolic benefits. Of particular interest are cytokines capable of fat browning. Irisin, derived from FNDC5, is an exercise-induced myokine that drives brown-fat-like thermogenesis in murine white fat. Here we explored whether cold exposure is an afferent signal for irisin secretion in humans and compared it with FGF21, a brown adipokine in rodents. Cold exposure increased circulating irisin and FGF21. We found an induction of irisin secretion proportional to shivering intensity, in magnitude similar to exercise-stimulated secretion. FNDC5 and/or FGF21 treatment upregulated human adipocyte brown fat gene/protein expression and thermogenesis in a depot-specific manner. These results suggest exercise-induced irisin secretion could have evolved from shivering-related muscle contraction, serving to augment brown fat thermogenesis in concert with FGF21. Irisin-mediated muscle-adipose crosstalk may represent a thermogenic, cold-activated endocrine axis that is exploitable in obesity therapeutics development.
C1 [Lee, Paul; Linderman, Joyce D.; Smith, Sheila; Brychta, Robert J.; Wang, Juan; Idelson, Christopher; Perron, Rachel M.; Werner, Charlotte D.; Chen, Kong Y.; Celi, Francesco S.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Phan, Giao Q.; Kammula, Udai S.] NIH, Surg Branch, Bethesda, MD 20892 USA.
[Kebebew, Electron] NIH, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
[Pacak, Karel] NCI, NIH, Bethesda, MD 20892 USA.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Celi, FS (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
EM fsceli@vcu.edu
OI Chen, Kong/0000-0002-0306-1904
FU Australian National Health Medical Research Council (NHMRC) Early Career
Fellowship; Royal Australasian College of Physicians (RACP) Foundations
Diabetes Australia Fellowship; School of Medicine, University of
Queensland, Australia; NIDDK [Z01-DK047057-02, Z01-DK071044,
Z01-DK071013, Z01-DK071014]
FX P.L. was supported by an Australian National Health Medical Research
Council (NHMRC) Early Career Fellowship; the Royal Australasian College
of Physicians (RACP) Foundations Diabetes Australia Fellowship and
Bushell Travelling Fellowship; and the School of Medicine, University of
Queensland, Australia. This study was supported by the Intramural
Research Program of NIDDK, programs Z01-DK047057-02, Z01-DK071044,
Z01-DK071013, and Z01-DK071014.
NR 32
TC 187
Z9 192
U1 15
U2 78
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 4
PY 2014
VL 19
IS 2
BP 302
EP 309
DI 10.1016/j.cmet.2013.12.017
PG 8
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 304CE
UT WOS:000330722600015
PM 24506871
ER
PT J
AU Iyer, LM
Zhang, DP
de Souza, RF
Pukkila, PJ
Rao, A
Aravind, L
AF Iyer, Lakshminarayan M.
Zhang, Dapeng
de Souza, Robson F.
Pukkila, Patricia J.
Rao, Anjana
Aravind, L.
TI Lineage-specific expansions of TET/JBP genes and a new class of DNA
transposons shape fungal genomic and epigenetic landscapes
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE methylcytosine; fungal evolution; DNA modification; genomic association
ID COPRINUS-CINEREUS; COMPLEX MODIFICATIONS; STRUCTURE PREDICTION;
PHYLOGENETIC TREES; EVOLUTION; METHYLATION; ELEMENTS; SYSTEMS;
TRANSCRIPTION; ELIMINATION
AB TET/JBP dioxygenases oxidize methylpyrimidines in nucleic acids and are implicated in generation of epigenetic marks and potential intermediates for DNA demethylation. We show that TET/JBP genes are lineage-specifically expanded in all major clades of basidiomycete fungi, with the majority of copies predicted to encode catalytically active proteins. This pattern differs starkly from the situation in most other organisms that possess just a single or a few copies of the TET/JBP family. In most basidiomycetes, TET/JBP genes are frequently linked to a unique class of transposons, KDZ (Kyakuja, Dileera, and Zisupton) and appear to have dispersed across chromosomes along with them. Several of these elements typically encode additional proteins, including a divergent version of the HMG domain. Analysis of their transposases shows that they contain a previously uncharacterized version of the RNase H fold with multiple distinctive Zn-chelating motifs and a unique insert, which are predicted to play roles in structural stabilization and target sequence recognition, respectively. We reconstruct the complex evolutionary history of TET/JBPs and associated transposons as involving multiple rounds of expansion with concomitant lineage sorting and loss, along with several capture events of TET/JBP genes by different transposon clades. On a few occasions, these TET/JBP genes were also laterally transferred to certain Ascomycota, Glomeromycota, Viridiplantae, and Amoebozoa. One such is an inactive version, calnexin-independence factor 1 (Cif1), from Schizosaccharomyces pombe, which has been implicated in inducing an epigenetically transmitted prion state. We argue that this unique transposon-TET/JBP association is likely to play important roles in speciation during evolution and epigenetic regulation.
C1 [Iyer, Lakshminarayan M.; Zhang, Dapeng; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[de Souza, Robson F.] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, BR-05508900 Sao Paulo, Brazil.
[Pukkila, Patricia J.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
[Rao, Anjana] Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA.
[Rao, Anjana] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA.
RP Rao, A (reprint author), Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA.
EM arao@liai.org; aravind@ncbi.nlm.nih.gov
FU Intramural Research Program of the US Department of Health and Human
Services, National Institutes of Health, National Library of Medicine
FX This work was funded by the Intramural Research Program of the US
Department of Health and Human Services, National Institutes of Health,
National Library of Medicine (L.M.I., D.Z., and L.A.).
NR 42
TC 11
Z9 11
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 4
PY 2014
VL 111
IS 5
BP 1676
EP 1683
DI 10.1073/pnas.1321818111
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 302FL
UT WOS:000330587600024
PM 24398522
ER
PT J
AU Liu, Y
Yang, YR
Tang, TS
Zhang, H
Wang, ZF
Friedberg, E
Yang, W
Guo, CX
AF Liu, Yang
Yang, Yeran
Tang, Tie-Shan
Zhang, Hui
Wang, Zhifeng
Friedberg, Errol
Yang, Wei
Guo, Caixia
TI Variants of mouse DNA polymerase. reveal a mechanism of efficient and
accurate translesion synthesis past a benzo[a] pyrene dG adduct
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE translesion DNA synthesis; polycyclic aromatic hydrocarbons
ID ERROR-FREE BYPASS; Y-FAMILY; MAMMALIAN-CELLS; LESION-BYPASS;
ACTIVE-SITE; STRUCTURAL BASIS; DIOL EPOXIDE; KAPPA; OPPOSITE;
REPLICATION
AB DNA polymerase kappa (Pol kappa) is the only known Y-family DNA polymerase that bypasses the 10S (+)-trans-anti-benzo[a] pyrene diol epoxide (BPDE)-N-2-deoxyguanine adducts efficiently and accurately. The unique features of Pol kappa, a large structure gap between the catalytic core and little finger domain and a 90-residue addition at the N terminus known as the N-clasp, may give rise to its special translesion capability. We designed and constructed two mouse Pol kappa variants, which have reduced gap size on both sides [Pol kappa Gap Mutant (PGM) 1] or one side flanking the template base (PGM2). These Pol kappa variants are nearly as efficient as WT in normal DNA synthesis, albeit with reduced accuracy. However, PGM1 is strongly blocked by the 10S (+)-trans-anti-BPDE-N-2-dG lesion. Steady-state kinetic measurements reveal a significant reduction in efficiency of dCTP incorporation opposite the lesion by PGM1 and a moderate reduction by PGM2. Consistently, Pol.-deficient cells stably complemented with PGM1 GFP-Pol kappa remained hypersensitive to BPDE treatment, and complementation with WT or PGM2 GFP-Pol kappa restored BPDE resistance. Furthermore, deletion of the first 51 residues of the N-clasp in mouse Pol kappa (mPol(kappa 52-516)) leads to reduced polymerization activity, and the mutant PGM2(52-516) but not PGM1(52-516) can partially compensate the N-terminal deletion and restore the catalytic activity on normal DNA. However, neither WT nor PGM2 mPol(kappa 52-516) retains BPDE bypass activity. We conclude that the structural gap physically accommodates the bulky aromatic adduct and the N-clasp is essential for the structural integrity and flexibility of Pol. during translesion synthesis.
C1 [Liu, Yang; Yang, Yeran; Zhang, Hui; Wang, Zhifeng; Guo, Caixia] Chinese Acad Sci, Beijing Inst Genom, Lab Canc Genom & Individualized Med, Beijing 100101, Peoples R China.
[Tang, Tie-Shan] Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China.
[Friedberg, Errol] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA.
[Yang, Wei] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Yang, W (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM weiy@mail.nih.gov; guocx@big.ac.cn
RI Yang, Wei/D-4926-2011
OI Yang, Wei/0000-0002-3591-2195
FU Chinese National 973 Project [2013CB945000, 2011CB944302, 2012CB944702];
Natural Science Foundation of China [30970588, 31170730, 81371415,
31300658, 31100557]; National Institutes of Health Intramural Program
[DK036146-07]; Chinese Academy of Sciences "OneHundred-Talent Program";
State Key Laboratory of Biomembrane and Membrane Biotechnology
FX The authors thank Dr. N. Geacintov for providing the BPDE modified
oligodeoxynucleotide and advice on fidelity assay, Drs. S. Broyde and L.
Lior-Hoffmann for the molecular simulated models of Pol.-BPDE-dG
complex, Dr. H. Wang for BPDE reagents, Dr. T. Ogi for advice on
establishment of stable cell lines, X. Zhang for assistance in cell
culture, and Drs. Y. Zhang and P. Fischhaber for helpful discussion.
This work was supported by Chinese National 973 Project Grants
2013CB945000, 2011CB944302, and 2012CB944702; Natural Science Foundation
of China Grants 30970588, 31170730, 81371415, 31300658, and 31100557;
National Institutes of Health Intramural Program DK036146-07; the
Chinese Academy of Sciences "OneHundred-Talent Program"; and the State
Key Laboratory of Biomembrane and Membrane Biotechnology.
NR 49
TC 15
Z9 15
U1 0
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 4
PY 2014
VL 111
IS 5
BP 1789
EP 1794
DI 10.1073/pnas.1324168111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 302FL
UT WOS:000330587600043
PM 24449898
ER
PT J
AU Keadle, SK
Lyden, K
Hickey, A
Ray, EL
Fowke, JH
Freedson, PS
Matthews, CE
AF Keadle, Sarah Kozey
Lyden, Kate
Hickey, Amanda
Ray, Evan L.
Fowke, Jay H.
Freedson, Patty S.
Matthews, Charles E.
TI Validation of a previous day recall for measuring the location and
purpose of active and sedentary behaviors compared to direct observation
SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY
LA English
DT Article
DE Exposure measurement; Physical activity; Behavioral epidemiology
ID ECOLOGICAL MOMENTARY ASSESSMENT; PHYSICAL-ACTIVITY; WEARABLE CAMERAS;
BUILT ENVIRONMENT; UNITED-STATES; TIME SPENT; ADULTS; HEALTH;
ACCELEROMETER; QUESTIONNAIRES
AB Purpose: Gathering contextual information (i.e., location and purpose) about active and sedentary behaviors is an advantage of self-report tools such as previous day recalls (PDR). However, the validity of PDR's for measuring context has not been empirically tested. The purpose of this paper was to compare PDR estimates of location and purpose to direct observation (DO).
Methods: Fifteen adult (18-75 y) and 15 adolescent (12-17 y) participants were directly observed during at least one segment of the day (i.e., morning, afternoon or evening). Participants completed their normal daily routine while trained observers recorded the location (i.e., home, community, work/school), purpose (e. g., leisure, transportation) and whether the behavior was sedentary or active. The day following the observation, participants completed an unannounced PDR. Estimates of time in each context were compared between PDR and DO. Intra-class correlations (ICC), percent agreement and Kappa statistics were calculated.
Results: For adults, percent agreement was 85% or greater for each location and ICC values ranged from 0.71 to 0.96. The PDR-reported purpose of adults' behaviors were highly correlated with DO for household activities and work (ICCs of 0.84 and 0.88, respectively). Transportation was not significantly correlated with DO (ICC = -0.08). For adolescents, reported classification of activity location was 80.8% or greater. The ICCs for purpose of adolescents' behaviors ranged from 0.46 to 0.78. Participants were most accurate in classifying the location and purpose of the behaviors in which they spent the most time.
Conclusions: This study suggests that adults and adolescents can accurately report where and why they spend time in behaviors using a PDR. This information on behavioral context is essential for translating the evidence for specific behavior-disease associations to health interventions and public policy.
C1 [Keadle, Sarah Kozey; Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Keadle, Sarah Kozey] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA.
[Lyden, Kate] Univ Colorado Denver, Div Endocrinol Metab & Diabet, Aurora, CO 80045 USA.
[Hickey, Amanda; Freedson, Patty S.] Univ Massachusetts, Dept Kinesiol, Amherst, MA 01003 USA.
[Ray, Evan L.] Univ Massachusetts, Dept Math & Stat, Amherst, MA 01003 USA.
[Fowke, Jay H.] Vanderbilt Univ, Ctr Med, Dept Med, Div Epidemiol, Nashville, TN 37232 USA.
RP Keadle, SK (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM sarah.keadle@nih.gov
RI matthews, Charles/E-8073-2015;
OI matthews, Charles/0000-0001-8037-3103; Keadle, Sarah/0000-0002-9569-9306
FU [R01 NR011477]
FX Funded by: R01 NR011477.
NR 41
TC 5
Z9 5
U1 4
U2 28
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5868
J9 INT J BEHAV NUTR PHY
JI Int. J. Behav. Nutr. Phys. Act.
PD FEB 3
PY 2014
VL 11
AR 12
DI 10.1186/1479-5868-11-12
PG 11
WC Nutrition & Dietetics; Physiology
SC Nutrition & Dietetics; Physiology
GA AD0NR
UT WOS:000332931600001
ER
PT J
AU Appaiahgari, MB
Glass, R
Singh, S
Taneja, S
Rongsen-Chandola, T
Bhandari, N
Mishra, S
Vrati, S
AF Appaiahgari, Mohan Babu
Glass, Roger
Singh, Shakti
Taneja, Sunita
Rongsen-Chandola, Temsunaro
Bhandari, Nita
Mishra, Sukhdev
Vrati, Sudhanshu
TI Transplacental rotavirus IgG interferes with immune response to live
oral rotavirus vaccine ORV-116E in Indian infants
SO VACCINE
LA English
DT Article
DE Maternal antibody; Dose; Seroconversion; IgA; Rotavirus; Vaccine
ID ATTENUATED HUMAN ROTAVIRUS; B-CELL RESPONSES; MATERNAL ANTIBODIES;
CONTROLLED-TRIAL; SAFETY; IMMUNOGENICITY; INFECTION; EFFICACY; TITER;
IMMUNIZATION
AB The lower immune response and efficacy of live oral rotavirus (RV) vaccines tested in developing countries maybe due in part to high levels of pre-existing RV antibodies transferred to the infant from mother via the placenta. The candidate RV vaccine strain 116E was isolated from a newborn indicating that it might grow well even in the presence of this transplacental rotavirus antibody. Since the immune response to this vaccine among infants in the Indian subcontinent has been greater than that of the commercially licensed vaccines, we questioned whether this might be due to the ability of RV 116E to grow well in infants despite the presence of maternal RV antibody. To this end, we tested pre-immunization sera from Indian infants enrolled in a phase Ia/IIb trial of candidate RV vaccine ORV-116E for transplacental RV IgG to see whether it affected the immune responses and seroconversion to the vaccine. We found that the high titers of transplacental RV IgG diminished the immune responses of infants to ORV-116E vaccine. However, the vaccine was able to overcome the inhibitory effect of this RV IgG in a dose-dependent manner. This report clearly demonstrates the interference of maternal antibody on RV vaccine immunogenicity in infants in a field study as well as the ability of ORV-116E to overcome this interference when used at a higher dose. (C) 2013 Published by Elsevier Ltd.
C1 [Appaiahgari, Mohan Babu; Vrati, Sudhanshu] Translat Hlth Sci & Technol Inst, Vaccine & Infect Dis Res Ctr, Gurgaon 122016, India.
[Glass, Roger] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Singh, Shakti; Taneja, Sunita; Rongsen-Chandola, Temsunaro; Bhandari, Nita] Soc Appl Studies, New Delhi 110016, India.
[Mishra, Sukhdev] Translat Hlth Sci & Technol Inst, Clin Dev Serv Agcy, Gurgaon 122016, India.
[Vrati, Sudhanshu] Natl Inst Immunol, New Delhi 110067, India.
RP Vrati, S (reprint author), Translat Hlth Sci & Technol Inst, Vaccine & Infect Dis Res Ctr, 496 Udyog Vihar Phase III, Gurgaon 122016, India.
EM vrati@thsti.res.in
RI singh, shakti/D-4070-2014
OI singh, shakti/0000-0001-6521-0998
FU Department of Biotechnology, Govt. of India
FX We thank Duncan Steele and John Clemens for critical reading of the
manuscript and valuable comments. This work was supported by the core
grant provided by the Department of Biotechnology, Govt. of India to the
National Institute of Immunology and the Translational Health Science
and Technology Institute.
NR 40
TC 19
Z9 19
U1 1
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD FEB 3
PY 2014
VL 32
IS 6
BP 651
EP 656
DI 10.1016/j.vaccine.2013.12.017
PG 6
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AB0SH
UT WOS:000331501900003
PM 24374502
ER
PT J
AU Johnson, MJ
Bjorkstrom, NK
Petrovas, C
Liang, F
Gall, JGD
Lore, K
Koup, RA
AF Johnson, Matthew J.
Bjorkstrom, Niklas K.
Petrovas, Constantinos
Liang, Frank
Gall, Jason G. D.
Lore, Karin
Koup, Richard A.
TI Type I interferon-dependent activation of NK cells by rAd28 or rAd35,
but not rAd5, leads to loss of vector-insert expression
SO VACCINE
LA English
DT Article
DE Adenovirus; rAd28; rAd35
ID PLASMACYTOID DENDRITIC CELLS; APOPTOTIC CELLS; IMMUNE-RESPONSES; VACCINE
VECTOR; T-CELLS; GENE; IMMUNOGENICITY; SEROPREVALENCE; CYTOKINE; REGIONS
AB Vaccines constructed from rare-serotype recombinant adenovirus vectors (rAd) such as rAd serotype 28 (rAd28) and rAd35 are currently being explored as alternatives to rAd5-based vaccines because they circumvent the problems with pre-existing immunity that complicate the effectiveness of rAd5 vaccines. However, previous work has demonstrated that the immunogenicity of rAd28 and rAd35 is substantially lower than rAd5. Here we show that rAd28 and rAd35 increase apoptosis of antigen presenting cells (APCs), such as monocytes, relative to rAd5 and mock infected controls. APCs undergoing apoptosis showed an increased loss of vector-insert expression. Loss of vector-insert expression correlated with activation of NK cells, which resulted in apoptosis of co-cultured monocytes. Finally, we show that activation of NK cells is dependent on IFN alpha which is produced by exposure to rAd28 or rAd35, but not to rAd5. Taken together, these data demonstrate that IFN alpha-induced activation of NK cells leads to increased monocyte apoptosis and subsequent vector-insert loss. This may be a possible mechanism that results in reduced immunogenicity of rAd28 and rAd35-based vectors. Published by Elsevier Ltd.
C1 [Johnson, Matthew J.; Petrovas, Constantinos; Liang, Frank; Lore, Karin; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Johnson, Matthew J.] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA.
[Bjorkstrom, Niklas K.; Liang, Frank; Lore, Karin] Karolinska Inst, Ctr Infect Med, Dept Pathol, S-14186 Stockholm, Sweden.
[Bjorkstrom, Niklas K.; Liang, Frank; Lore, Karin] Karolinska Inst, Dept Med, S-14186 Stockholm, Sweden.
[Gall, Jason G. D.] GenVec Inc, Gaithersburg, MD 20878 USA.
RP Koup, RA (reprint author), NIH, Vaccine Res Ctr, 40 Convent Dr, Bethesda, MD 20892 USA.
EM rkoup@mail.nih.gov
OI Bjorkstrom, Niklas/0000-0002-0967-076X
FU Intramural NIH HHS [ZIA AI005073-10]
NR 26
TC 6
Z9 6
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD FEB 3
PY 2014
VL 32
IS 6
BP 717
EP 724
DI 10.1016/j.vaccine.2013.11.055
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AB0SH
UT WOS:000331501900013
PM 24325826
ER
PT J
AU Murphy, AP
Leopold, DA
Welchman, AE
AF Murphy, Aidan P.
Leopold, David A.
Welchman, Andrew E.
TI Perceptual memory drives learning of retinotopic biases for bistable
stimuli
SO FRONTIERS IN PSYCHOLOGY
LA English
DT Article
DE bistable; ambiguous figures; perceptual stabilization; cue recruitment;
associative learning
ID AMBIGUOUS PATTERNS; VISUAL-ADAPTATION; SENSORY MEMORY; EXPERIENCE;
MOTION; COMPETITION
AB The visual system exploits past experience at multiple timescales to resolve perceptual ambiguity in the retinal image. For example, perception of a bistable stimulus can be biased toward one interpretation over another when preceded by a brief presentation of a disambiguated version of the stimulus (positive priming) or through intermittent presentations of the ambiguous stimulus (stabilization). Similarly, prior presentations of unambiguous stimuli can be used to explicitly "train" a long-lasting association between a percept and a retinal location (perceptual association). These phenonema have typically been regarded as independent processes, with short-term biases attributed to perceptual memory and longer-term biases described as associative learning. Here we tested for interactions between these two forms of experience-dependent perceptual bias and demonstrate that short-term processes strongly influence long-term outcomes. We first demonstrate that the establishment of long-term perceptual contingencies does not require explicit training by unambiguous stimuli, but can arise spontaneously during the periodic presentation of brief, ambiguous stimuli. Using rotating Necker cube stimuli, we observed enduring, retinotopically specific perceptual biases that were expressed from the outset and remained stable for up to 40 min, consistent with the known phenomenon of perceptual stabilization. Further, bias was undiminished after a break period of 5 min, but was readily reset by interposed periods of continuous, as opposed to periodic, ambiguous presentation. Taken together, the results demonstrate that perceptual biases can arise naturally and may principally reflect the brain's tendency to favor recent perceptual interpretation at a given retinal location. Further, they suggest that an association between retinal location and perceptual state, rather than a physical stimulus, is sufficient to generate long-term biases in perceptual organization.
C1 [Murphy, Aidan P.; Welchman, Andrew E.] Univ Birmingham, Sch Psychol, Binocular Vis Lab, Birmingham B15 2TT, W Midlands, England.
[Murphy, Aidan P.; Leopold, David A.] NIMH, Neuropsychol Lab, Sect Cognit Neurophysiol & Imaging, Bethesda, MD 20892 USA.
[Welchman, Andrew E.] Univ Cambridge, Dept Psychol, Cambridge, England.
RP Murphy, AP (reprint author), NIMH, Neuropsychol Lab, Sect Cognit Neurophysiol & Imaging, Room B1-C60,Bldg 49,49 Convent Dr, Bethesda, MD 20892 USA.
EM murphyap@mail.nih.gov
RI Welchman, Andrew/B-7542-2013;
OI Welchman, Andrew/0000-0002-7559-3299; Leopold, David/0000-0002-1345-6360
FU Wellcome Trust [095183]
NR 42
TC 1
Z9 1
U1 1
U2 6
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-1078
J9 FRONT PSYCHOL
JI Front. Psychol.
PD FEB 3
PY 2014
VL 5
AR 60
DI 10.3389/fpsyg.2014.00060
PG 11
WC Psychology, Multidisciplinary
SC Psychology
GA AA7MC
UT WOS:000331280500001
PM 24550874
ER
PT J
AU Meyer, V
Dinkel, PD
Luo, Y
Yu, X
Wei, GH
Zheng, J
Eaton, GR
Ma, BY
Nussinov, R
Eaton, SS
Margittai, M
AF Meyer, Virginia
Dinkel, Paul D.
Luo, Yin
Yu, Xiang
Wei, Guanghong
Zheng, Jie
Eaton, Gareth R.
Ma, Buyong
Nussinov, Ruth
Eaton, Sandra S.
Margittai, Martin
TI Single Mutations in Tau Modulate the Populations of Fibril Conformers
through Seed Selection
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE Alzheimer's disease; conformation analysis; EPR spectroscopy; proteins;
tau fibrils
ID PAIRED HELICAL FILAMENTS; NEURODEGENERATIVE-DISEASES; FRONTOTEMPORAL
DEMENTIA; AMYLOID FIBRILS; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE;
BETA-STRUCTURE; 4-REPEAT TAU; PROTEIN; PROPAGATION
AB Seeded conversion of tau monomers into fibrils is a central step in the progression of tau pathology in Alzheimer's disease and other neurodegenerative disorders. Self-assembly is mediated by the microtubule binding repeats in tau. There are either three or four repeats present depending on the protein isoform. Here, double electron-electron resonance spectroscopy was used to investigate the conformational ensemble of four-repeat tau fibrils. Single point mutations at key positions in the protein (K280, P301S, P312I, D314I) markedly change the distribution of fibril conformers after template-assisted growth, whereas other mutations in the protein (I308M, S320F, G323I, G326I, Q336R) do not. These findings provide unprecedented insights into the seed selection of tau disease mutants and establish conformational compatibility as an important driving force in tau fibril propagation.
C1 [Meyer, Virginia; Dinkel, Paul D.; Eaton, Gareth R.; Eaton, Sandra S.; Margittai, Martin] Univ Denver, Dept Chem & Biochem, Denver, CO 80208 USA.
[Luo, Yin; Wei, Guanghong] Fudan Univ, State Key Lab Surface Phys, Key Lab Computat Phys Sci MOE, Shanghai 200433, Peoples R China.
[Luo, Yin; Wei, Guanghong] Fudan Univ, Dept Phys, Shanghai 200433, Peoples R China.
[Yu, Xiang; Zheng, Jie] Univ Akron, Dept Chem & Biomol Engn, Akron, OH 44325 USA.
[Ma, Buyong; Nussinov, Ruth] NCI, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick Natl Lab, Frederick, MD 21702 USA.
RP Margittai, M (reprint author), Univ Denver, Dept Chem & Biochem, Denver, CO 80208 USA.
EM martin.margittai@du.edu
RI Margittai, Martin/D-5039-2014; Ma, Buyong/F-9491-2011; Zheng,
Jie/B-5057-2013;
OI Margittai, Martin/0000-0003-1903-5927; Ma, Buyong/0000-0002-7383-719X;
Zheng, Jie/0000-0003-1547-3612; Eaton, Gareth R/0000-0001-7429-8469;
Eaton, Sandra S/0000-0002-2731-7986
FU National Institute of Neurological Disorders and Stroke [R01NS076619];
National Cancer Institute [HHSN261200800001E]; National Cancer Institute
Center for Cancer Research, National Science Foundation (CAREER)
[CBET-0952624, CBET-1158447]; National Natural Science Foundation of
China [11074047, 11274075, 91227102]
FX This project was supported by the National Institute of Neurological
Disorders and Stroke Grant R01NS076619 (to M. M.). This work was also
supported by the National Cancer Institute Contract (HHSN261200800001E),
the intramural research program of the National Cancer Institute Center
for Cancer Research, National Science Foundation (CAREER Award
CBET-0952624 and CBET-1158447; to J.Z.), and the National Natural
Science Foundation of China Grant (11074047, 11274075, and 91227102; to
G. W.). We thank Dr. Eric Hustedt for his assistance using GLADD, and
helpful discussions regarding analysis of DEER data.
NR 43
TC 17
Z9 17
U1 0
U2 28
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1433-7851
EI 1521-3773
J9 ANGEW CHEM INT EDIT
JI Angew. Chem.-Int. Edit.
PD FEB 3
PY 2014
VL 53
IS 6
BP 1590
EP 1593
DI 10.1002/anie.201308473
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 301UU
UT WOS:000330558400022
PM 24453187
ER
PT J
AU Luo, Q
Cheng, X
Holroyd, T
Xu, D
Carver, F
Blair, RJ
AF Luo, Qian
Cheng, Xi
Holroyd, Tom
Xu, Duo
Carver, Frederick
Blair, R. James
TI Theta band activity in response to emotional expressions and its
relationship with gamma band activity as revealed by MEG and advanced
beamformer source imaging
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE MEG; theta; gamma; emotion; event-related synchronization
ID PRIMARY VISUAL-CORTEX; WORKING-MEMORY TASK; NEURONAL OSCILLATIONS;
NEURAL MECHANISMS; CORTICAL NETWORKS; BEHAVING RAT; SYNCHRONIZATION;
AMYGDALA; FREQUENCY; ALPHA
AB Neuronal oscillations in the theta and gamma bands have been shown to be important for cognition. Here we examined the temporal and spatial relationship between the two frequency bands in emotional processing using magnetoencephalography and an advanced dynamic beamformer source imaging method called synthetic aperture magnetometry. We found that areas including the amygdala, visual and frontal cortex showed significant event-related synchronization in both bands, suggesting a functional association of neuronal oscillations in the same areas in the two bands. However, while the temporal profile in both bands was similar in the amygdala, the peak in gamma band power was much earlier within both visual and frontal areas. Our results do not support a traditional view that the localizations of lower and higher frequencies are spatially distinct. Instead, they suggest that in emotional processing, neuronal oscillations in the gamma and theta bands may reflect, at least in visual and frontal cortex either different but related functional processes or, perhaps more probably, different computational components of the same functional process.
C1 [Luo, Qian; Xu, Duo] St Louis Univ, Sch Med, Dept Neurosurg, St Louis, MO 63104 USA.
[Luo, Qian; Blair, R. James] NIMH, Unit Affect Cognit Neurosci, Bethesda, MD 20892 USA.
[Cheng, Xi] Lieber Inst Brain Dev, Baltimore, MD USA.
[Holroyd, Tom; Carver, Frederick] NIMH, MEG Core Facil, Bethesda, MD 20892 USA.
RP Luo, Q (reprint author), St Louis Univ, Sch Med, Dept Neurosurg, 1320 South Grand Blvd,1st Floor ODonnell Hall, St Louis, MO 63104 USA.
EM RBBT_L@yahoo.com
FU NIMH Intramural Research Program
FX This study is supported by NIMH Intramural Research Program.
NR 52
TC 2
Z9 2
U1 2
U2 8
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD FEB 3
PY 2014
VL 7
AR 940
DI 10.3389/fnhum.2013.00940
PG 8
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA 302XM
UT WOS:000330638400001
ER
PT J
AU Romero, R
Hassan, SS
Gajer, P
Tarca, AL
Fadrosh, DW
Nikita, L
Galuppi, M
Lamont, RF
Chaemsaithong, P
Miranda, J
Chaiworapongsa, T
Ravel, J
AF Romero, Roberto
Hassan, Sonia S.
Gajer, Pawel
Tarca, Adi L.
Fadrosh, Douglas W.
Nikita, Lorraine
Galuppi, Marisa
Lamont, Ronald F.
Chaemsaithong, Piya
Miranda, Jezid
Chaiworapongsa, Tinnakorn
Ravel, Jacques
TI The composition and stability of the vaginal microbiota of normal
pregnant women is different from that of non-pregnant women
SO MICROBIOME
LA English
DT Article
DE Community stability; Longitudinal sampling; Pregnancy; Vaginal
microbiome; Lactobacillus; Dynamics
ID 16S RIBOSOMAL-RNA; FEMALE GENITAL-TRACT; IMMUNODEFICIENCY-VIRUS TYPE-1;
GRADIENT GEL-ELECTROPHORESIS; LOW-BIRTH-WEIGHT; ASYMPTOMATIC BACTERIAL
VAGINOSIS; CHLAMYDIA-TRACHOMATIS INFECTION; CULTIVATION-INDEPENDENT
METHODS; SEXUALLY-TRANSMITTED-DISEASES; HORMONE REPLACEMENT THERAPY
AB Background: This study was undertaken to characterize the vaginal microbiota throughout normal human pregnancy using sequence-based techniques. We compared the vaginal microbial composition of non-pregnant patients with a group of pregnant women who delivered at term.
Results: A retrospective case-control longitudinal study was designed and included non-pregnant women (n = 32) and pregnant women who delivered at term (38 to 42 weeks) without complications (n = 22). Serial samples of vaginal fluid were collected from both non-pregnant and pregnant patients. A 16S rRNA gene sequence-based survey was conducted using pyrosequencing to characterize the structure and stability of the vaginal microbiota. Linear mixed effects models and generalized estimating equations were used to identify the phylotypes whose relative abundance was different between the two study groups. The vaginal microbiota of normal pregnant women was different from that of non-pregnant women (higher abundance of Lactobacillus vaginalis, L. crispatus, L. gasseri and L. jensenii and lower abundance of 22 other phylotypes in pregnant women). Bacterial community state type (CST) IV-B or CST IV-A characterized by high relative abundance of species of genus Atopobium as well as the presence of Prevotella, Sneathia, Gardnerella, Ruminococcaceae, Parvimonas, Mobiluncus and other taxa previously shown to be associated with bacterial vaginosis were less frequent in normal pregnancy. The stability of the vaginal microbiota of pregnant women was higher than that of non-pregnant women; however, during normal pregnancy, bacterial communities shift almost exclusively from one CST dominated by Lactobacillus spp. to another CST dominated by Lactobacillus spp.
Conclusion: We report the first longitudinal study of the vaginal microbiota in normal pregnancy. Differences in the composition and stability of the microbial community between pregnant and non-pregnant women were observed. Lactobacillus spp. were the predominant members of the microbial community in normal pregnancy. These results can serve as the basis to study the relationship between the vaginal microbiome and adverse pregnancy outcomes.
C1 [Romero, Roberto; Hassan, Sonia S.; Tarca, Adi L.; Nikita, Lorraine; Galuppi, Marisa; Lamont, Ronald F.; Chaemsaithong, Piya; Miranda, Jezid; Chaiworapongsa, Tinnakorn] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Res, Program Perinatal Res & Obstet,Perinatol Res Bran, Bethesda, MD 20892 USA.
[Romero, Roberto; Hassan, Sonia S.; Tarca, Adi L.; Nikita, Lorraine; Galuppi, Marisa; Lamont, Ronald F.; Chaemsaithong, Piya; Miranda, Jezid; Chaiworapongsa, Tinnakorn] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Res, Program Perinatal Res & Obstet,Perinatol Res Bran, Bethesda, MD 20892 USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI USA.
[Hassan, Sonia S.; Galuppi, Marisa; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA.
[Gajer, Pawel; Fadrosh, Douglas W.; Ravel, Jacques] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
[Gajer, Pawel; Ravel, Jacques] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Lamont, Ronald F.] Univ Southern Denmark, Dept Obstet & Gynaecol, Odense, Denmark.
[Lamont, Ronald F.] UCL, Northwick Pk Inst Med Res Campus, Div Surg, London, England.
RP Romero, R (reprint author), NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Res, Program Perinatal Res & Obstet,Perinatol Res Bran, Bldg 10, Bethesda, MD 20892 USA.
EM romeror@mail.nih.gov; jravel@som.umaryland.edu
OI Ravel, Jacques/0000-0002-0851-2233
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This work was funded, in part, by the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS. The authors
wish to acknowledge the contributions of the patients who volunteered
for these studies, the medical and healthcare personnel involved in the
research effort, and colleagues who contributed to the discussions which
eventually led to the conduct of the study. We are particularly grateful
to Dr Sharon Hillier of the University of Pittsburgh, Dr Jack Sobel of
Wayne State University, Dr David Relman of Stanford University and Dr
Sorin Draghici of Wayne State University.
NR 271
TC 80
Z9 85
U1 11
U2 31
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2049-2618
J9 MICROBIOME
JI Microbiome
PD FEB 3
PY 2014
VL 2
AR 4
DI 10.1186/2049-2618-2-4
PG 19
WC Microbiology
SC Microbiology
GA CU0EN
UT WOS:000363188900001
PM 24484853
ER
PT J
AU Patterson, MC
Brown, TM
Zaccariello, MJ
Thurm, A
Porter, FD
AF Patterson, Marc C.
Brown, Tanya M.
Zaccariello, Michael J.
Thurm, Audrey
Porter, Forbes D.
TI Longitudinal study of cognition in Niemann-Pick disease type C
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 10th Annual Research Meeting and World Symposium of the
Lysosomal-Disease-Network (LDN)
CY FEB 10-13, 2014
CL San Diego, CA
SP Lysosomal Dis Network
C1 [Patterson, Marc C.; Brown, Tanya M.; Zaccariello, Michael J.] Mayo Clin, Rochester, MN USA.
[Thurm, Audrey; Porter, Forbes D.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2014
VL 111
IS 2
MA 192
BP S85
EP S85
DI 10.1016/j.ymgme.2013.12.204
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 304KO
UT WOS:000330746000193
ER
PT J
AU Brown, ML
Klabunde, CN
Cronin, KA
White, MC
Richardson, LC
McNeel, TS
AF Brown, Martin L.
Klabunde, Carrie N.
Cronin, Kathy A.
White, Mary C.
Richardson, Lisa C.
McNeel, Timothy S.
TI Challenges in Meeting Healthy People 2020 Objectives for Cancer-Related
Preventive Services, National Health Interview Survey, 2008 and 2010
SO PREVENTING CHRONIC DISEASE
LA English
DT Article
ID UNITED-STATES; PUBLIC-HEALTH; METAANALYSIS; PHYSICIANS; ACCURACY; TRENDS
AB Introduction Healthy People (HP) is the US program that formulates and tracks national health objectives for the nation. The National Health Interview Survey (NHIS) is a designated data source for setting and evaluating several HP targets in cancer. We used data from the 2008 and 2010 NHIS to provide a benchmark for national performance toward meeting HP 2020 cancer-related objectives.
Methods HP 2020 cancer screening, provider counseling, and health care access objectives were selected. For each objective, NHIS measures for the overall population and several sociodemographic subgroups were calculated; the findings were compared with established HP 2020 targets.
Results From 2008 to 2010, rates of breast and cervical cancer screening declined slightly while colorectal cancer screening rates increased by 7 percentage points. Rates of cancer screening and provider counseling were below HP targets. Meeting HP targets seems less likely for subgroups characterized by low income, no health insurance, or no usual source of care. Meeting HP targets for access to health services will require an increase of 18 percentage points in the proportion of persons under age 65 with health insurance coverage and an increase of 10 percentage points in the proportion aged 18 to 64 with a usual source of care.
Conclusion Whether HP objectives for cancer screening and health care access are met may depend on implementation of health care reform measures that improve access to and coordination of care. Better integration of clinical health care and community-based efforts for delivering high-quality screening and treatment services and elimination of health disparities are also needed.
C1 [Brown, Martin L.; Cronin, Kathy A.] NCI, Bethesda, MD 20892 USA.
[White, Mary C.; Richardson, Lisa C.] Ctr Dis Control & Prevent, Atlanta, GA 30322 USA.
[McNeel, Timothy S.] Informat Management Serv Inc, Beltsville, MD 20705 USA.
RP Klabunde, CN (reprint author), 9606 Med Ctr Dr,MSC 9762, Bethesda, MD 20892 USA.
EM KlabundC@mail.nih.gov
RI White, Mary /C-9242-2012
OI White, Mary /0000-0002-9826-3962
NR 28
TC 8
Z9 8
U1 0
U2 4
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1545-1151
J9 PREV CHRONIC DIS
JI Prev. Chronic Dis.
PD FEB
PY 2014
VL 11
AR 130174
DI 10.5888/pcd11.130174
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AR3XE
UT WOS:000343521700003
PM 24576396
ER
PT J
AU Hurtado, M
Spinner, JR
Yang, MS
Evensen, C
Windham, A
Ortiz, G
Tracy, R
Ivy, ED
AF Hurtado, Margarita
Spinner, Jovonni R.
Yang, Manshu
Evensen, Christian
Windham, Amy
Ortiz, Gloria
Tracy, Rachael
Ivy, Edward Donnell
TI Knowledge and Behavioral Effects in Cardiovascular Health: Community
Health Worker Health Disparities Initiative, 2007-2010
SO PREVENTING CHRONIC DISEASE
LA English
DT Article
ID HEART-DISEASE; STROKE
AB Introduction Cardiovascular disease is the leading cause of death in the United States, and disparities in cardiovascular health exist among African Americans, American Indians, Hispanics, and Filipinos. The Community Health Worker Health Disparities Initiative of the National Heart, Lung, and Blood Institute (NHLBI) includes culturally tailored curricula taught by community health workers (CHWs) to improve knowledge and heart-healthy behaviors in these racial/ethnic groups.
Methods We used data from 1,004 community participants in a 10-session curriculum taught by CHWs at 15 sites to evaluate the NHLBI's health disparities initiative by using a 1-group pretest posttest design. The curriculum addressed identification and management of cardiovascular disease risk factors. We used linear mixed effects and generalized linear mixed effects models to examine results.
Results Average participant age was 48; 75% were female, 50% were Hispanic, 35% were African American, 8% were Filipino, and 7% were American Indian. Twenty-three percent reported a history of diabetes, and 37% reported a family history of heart disease. Correct pretest to posttest knowledge scores increased from 48% to 74% for heart healthy knowledge. The percentage of participants at the action or maintenance stage of behavior change increased from 41% to 85%.
Conclusion Using the CHW model to implement community education with culturally tailored curricula may improve heart health knowledge and behaviors among minorities. Further studies should examine the influence of such programs on clinical risk factors for cardiovascular disease.
C1 [Spinner, Jovonni R.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Hurtado, Margarita; Yang, Manshu; Evensen, Christian; Windham, Amy] Amer Inst Res, Washington, DC USA.
[Ortiz, Gloria; Tracy, Rachael; Ivy, Edward Donnell] NIH, Bethesda, MD 20892 USA.
RP Spinner, JR (reprint author), NHLBI, NIH, 31 Ctr Dr,MSC 2480,Room 4A29D, Bethesda, MD 20892 USA.
EM Jovonni.spinner@nih.gov
FU National Institutes of Health, NHLBI [GS-10E-0112J]
FX This research was supported by the National Institutes of Health, NHLBI
contract GS-10E-0112J (Division for the Application of Research
Discoveries [DARD] [Program Evaluation]). We thank Dr Denise
Simons-Morton, Ms Karen Donato, and Dr Robinson Fulwood of NHLBI DARD
for their support of the research and review of the manuscript. We also
gratefully acknowledge the participation of the community sites, the
CHWs, and the program participants, without whom this research could not
have been carried out.
NR 21
TC 2
Z9 2
U1 1
U2 9
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1545-1151
J9 PREV CHRONIC DIS
JI Prev. Chronic Dis.
PD FEB
PY 2014
VL 11
AR 130250
DI 10.5888/pcd11.130250WJ
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AR3XE
UT WOS:000343521700006
PM 24524426
ER
PT J
AU Sanchez, M
Purcell, EP
Michie, JS
Tsakraklides, SP
La Porta, M
Vinson, C
AF Sanchez, Michael
Purcell, E. Peyton
Michie, Joan S.
Tsakraklides, Sophia P.
La Porta, Madeline
Vinson, Cynthia
TI Building Cancer Control Capacity: a Mixed-Method Evaluation of the
Research to Reality (R2R) Mentorship Program
SO PREVENTING CHRONIC DISEASE
LA English
DT Article
ID INTERVENTIONS; HEALTH
AB In 2011, the National Cancer Institute launched the Research to Reality (R2R) Pilot Mentorship Program to enhance mentees' core evidence-based public health (EBPH) competencies. In this article, we describe the program and its evaluation results and the program's ability to improve participants' EBPH competencies and appropriateness of program components. Program evaluation consisted of a pre/post program competency questionnaire and interviews with mentees, mentors, mentees' supervisors, and program staff. Mentees reported the same or higher rating in every competency at end of the program, with average increase of 0.6 points on a 4-point scale; the greatest improvements were seen in policy development/program planning Mentorship programs are a promising strategy to develop EBPH competencies, provide guidance, and disseminate and adapt evidence-based interventions within real-world context.
C1 [Sanchez, Michael; La Porta, Madeline; Vinson, Cynthia] NCI, Rockville, MD 20850 USA.
[Purcell, E. Peyton] SAIC Frederick Inc, Clin Res Directorate CMRP, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Michie, Joan S.; Tsakraklides, Sophia P.] WESTAT Corp, Rockville, MD 20850 USA.
RP Sanchez, M (reprint author), NCI, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM sanchezgarciama@mail.nih.gov
FU NCI, National Institutes of Health [HHSN261200800001E]
FX This project was funded in whole or in part with federal funds from the
NCI, 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 US government.
NR 11
TC 0
Z9 0
U1 0
U2 3
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1545-1151
J9 PREV CHRONIC DIS
JI Prev. Chronic Dis.
PD FEB
PY 2014
VL 11
AR 130275
DI 10.5888/pcd11.130275
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AR3XE
UT WOS:000343521700008
ER
PT J
AU Clarke, LP
Nordstrom, RJ
Zhang, HM
Tandon, P
Zhang, YT
Redmond, G
Farahani, K
Kelloff, G
Henderson, L
Shankar, L
Deye, J
Capala, J
Jacobs, P
AF Clarke, Laurence P.
Nordstrom, Robert J.
Zhang, Huiming
Tandon, Pushpa
Zhang, Yantian
Redmond, George
Farahani, Keyvan
Kelloff, Gary
Henderson, Lori
Shankar, Lalitha
Deye, James
Capala, Jacek
Jacobs, Paula
TI The Quantitative Imaging Network: NCI's Historical Perspective and
Planned Goals
SO TRANSLATIONAL ONCOLOGY
LA English
DT Article
AB The purpose of this editorial is to provide a brief history of National Institutes of Health National Cancer Institute (NCI) workshops as related to quantitative imaging within the oncology setting. The editorial will then focus on the recently supported NCI initiatives, including the Quantitative Imaging Network (QIN) initiative and its organizational structure, including planned research goals and deliverables. The publications in this issue of Translational Oncology come from many of the current members of this QIN research network.
C1 [Clarke, Laurence P.; Nordstrom, Robert J.; Zhang, Huiming; Tandon, Pushpa; Zhang, Yantian; Redmond, George; Farahani, Keyvan; Kelloff, Gary; Henderson, Lori; Shankar, Lalitha; Deye, James; Capala, Jacek; Jacobs, Paula] NCI, Bethesda, MD 20892 USA.
RP Clarke, LP (reprint author), Suite 6066,EPN 6130 Executive Blvd, Bethesda, MD 20892 USA.
EM lclarke@mail.nih.gov
NR 6
TC 14
Z9 14
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1944-7124
EI 1936-5233
J9 TRANSL ONCOL
JI Transl. Oncol.
PD FEB
PY 2014
VL 7
IS 1
BP 1
EP 4
DI 10.1593/tlo.13832
PG 4
WC Oncology
SC Oncology
GA AQ3ID
UT WOS:000342684300001
PM 24772201
ER
PT J
AU Kalpathy-Cramer, J
Freymann, JB
Kirby, JS
Kinahan, PE
Prior, FW
AF Kalpathy-Cramer, Jayashree
Freymann, John Blake
Kirby, Justin Stephen
Kinahan, Paul Eugene
Prior, Fred William
TI Quantitative Imaging Network: Data Sharing and Competitive Algorithm
Validation Leveraging The Cancer Imaging Archive
SO TRANSLATIONAL ONCOLOGY
LA English
DT Article
ID RESOURCE; THERAPY; SYSTEMS
AB The Quantitative Imaging Network (QIN), supported by the National Cancer Institute, is designed to promote research and development of quantitative imaging methods and candidate biomarkers for the measurement of tumor response in clinical trial settings. An integral aspect of the QIN mission is to facilitate collaborative activities that seek to develop best practices for the analysis of cancer imaging data. The QIN working groups and teams are developing new algorithms for image analysis and novel biomarkers for the assessment of response to therapy. To validate these algorithms and biomarkers and translate them into clinical practice, algorithms need to be compared and evaluated on large and diverse data sets. Analysis competitions, or "challenges," are being conducted within the QIN as a means to accomplish this goal. The QIN has demonstrated, through its leveraging of The Cancer Imaging Archive (TCIA), that data sharing of clinical images across multiple sites is feasible and that it can enable and support these challenges. In addition to Digital Imaging and Communications in Medicine (DICOM) imaging data, many TCIA collections provide linked clinical, pathology, and "ground truth" data generated by readers that could be used for further challenges. The TCIA-QIN partnership is a successful model that provides resources for multisite sharing of clinical imaging data and the implementation of challenges to support algorithm and biomarker validation.
C1 [Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 01940 USA.
[Kalpathy-Cramer, Jayashree] Harvard Univ, Sch Med, Boston, MA USA.
[Freymann, John Blake; Kirby, Justin Stephen] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, CMRP, Clin Res Directorate, Frederick, MD USA.
[Kinahan, Paul Eugene] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
[Prior, Fred William] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA.
RP Kalpathy-Cramer, J (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 01940 USA.
EM kalpathy@nmr.mgh.harvard.edu
OI Kalpathy-Cramer, Jayashree/0000-0001-8906-9618
FU National Cancer Institute, National Institutes of Health (NIH)
[HHSN261200800001E]; NIH grants [U01CA154602, R00LM009889, ST13-4130];
NIH grant [U01CA148131, 24XS036-004]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health (NIH),
under Contract No. HHSN261200800001E. The content of this publication
does not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government.
J.K.-C. is funded in part by the NIH grants U01CA154602 and R00LM009889
and a contract ST13-4130. P.E.K. is funded in part by the NIH grant
U01CA148131 and Contract 24XS036-004.
NR 33
TC 8
Z9 8
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1944-7124
EI 1936-5233
J9 TRANSL ONCOL
JI Transl. Oncol.
PD FEB
PY 2014
VL 7
IS 1
BP 147
EP 152
DI 10.1593/tlo.13862
PG 6
WC Oncology
SC Oncology
GA AQ3ID
UT WOS:000342684300018
PM 24772218
ER
PT J
AU Bolnick, AD
Bolnick, JM
Kilburn, BA
Armant, DR
AF Bolnick, Alan D.
Bolnick, Jay M.
Kilburn, Brian A.
Armant, D. Randall
TI Low Molecular Weight Heparin Promotes Extravillous Differentiation and
Prevents Apoptosis of First Trimester Human Trophoblast Cells Through
HBEGF-mediated Signaling
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 62nd Annual Meeting of the Pacific-Coast-Reproductive-Society (PCRS)
CY MAR 19-23, 2014
CL Indian Wells, CA
SP Pacific Coast Reprod Soc
C1 [Bolnick, Alan D.; Bolnick, Jay M.; Kilburn, Brian A.; Armant, D. Randall] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Armant, D. Randall] NICHD, Program Reprod & Adult Endocrinol, NIH, DHHS, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD FEB
PY 2014
VL 101
IS 2
SU S
MA P-3
BP E8
EP E8
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AP8SX
UT WOS:000342350300012
ER
PT J
AU Bolnick, JM
Bolnick, AD
Kilburn, BA
Armant, DR
AF Bolnick, Jay M.
Bolnick, Alan D.
Kilburn, Brian A.
Armant, D. Randall
TI Sildenafil Rescues First Trimester Trophoblasts from Acute Alcohol
Exposure Through Downstream Protein kinase G Signaling
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 62nd Annual Meeting of the Pacific-Coast-Reproductive-Society (PCRS)
CY MAR 19-23, 2014
CL Indian Wells, CA
SP Pacific Coast Reprod Soc
C1 [Bolnick, Jay M.; Bolnick, Alan D.; Kilburn, Brian A.; Armant, D. Randall] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Dept Obstet & Gynecol, Detroit, MI USA.
[Armant, D. Randall] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Dept Anat & Cell Biol, Detroit, MI USA.
[Armant, D. Randall] NICHD, Program Reprod & Adult Endocrinol, NIH, DHHS, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD FEB
PY 2014
VL 101
IS 2
SU S
MA P-29
BP E19
EP E20
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AP8SX
UT WOS:000342350300038
ER
PT J
AU Gulley, JL
Madan, RA
Tsang, KY
Jochems, C
Marte, JL
Farsaci, B
Tucker, JA
Hodge, JW
Liewehr, DJ
Steinberg, SM
Heery, CR
Schlom, J
AF Gulley, James L.
Madan, Ravi A.
Tsang, Kwong Y.
Jochems, Caroline
Marte, Jennifer L.
Farsaci, Benedetto
Tucker, Jo A.
Hodge, James W.
Liewehr, David J.
Steinberg, Seth M.
Heery, Christopher R.
Schlom, Jeffrey
TI Immune Impact Induced by PROSTVAC (PSA-TRICOM), a Therapeutic Vaccine
for Prostate Cancer
SO CANCER IMMUNOLOGY RESEARCH
LA English
DT Article
ID PHASE-I TRIAL; T-CELLS; ANTITUMOR RESPONSES; PERIPHERAL-BLOOD; ANTIGEN
CASCADE; VIRAL VACCINE; TUMOR; SURVIVAL; COMBINATION; LYMPHOCYTES
AB PSA-TRICOM (PROSTVAC) is a novel vector-based vaccine designed to generate a robust immune response against prostate-specific antigen (PSA)-expressing tumor cells. The purpose of this report is to present an overview of both published studies and new data in the evaluation of immune responses to the PSA-TRICOM vaccine platform, currently in phase III testing. Of 104 patients tested for T-cell responses, 57% (59/104) demonstrated a >= 2-fold increase in PSA-specific T cells 4 weeks after vaccine (median 5-fold increase) compared with pre-vaccine, and 68% (19/28) of patients tested mounted post-vaccine immune responses to tumor-associated antigens not present in the vaccine (antigen spreading). The PSA-specific immune responses observed 28 days after vaccine (i.e., likely memory cells) are quantitatively similar to the levels of circulating T cells specific for influenza seen in the same patients. Measurements of systemic immune response to PSA may underestimate the true therapeutic immune response (as this does not account for cells that have trafficked to the tumor) and does not include antigen spreading. Furthermore, although the entire PSA gene is the vaccine, only one epitope of PSA is evaluated in the T-cell responses. Because this therapeutic vaccine is directed at generating a cellular/Th1 immune response (T-cell costimulatory molecules and use of a viral vector), it is not surprising that less than 0.6% of patients (2/349) tested have evidence of PSA antibody induction following vaccine. This suggests that post-vaccine PSA kinetics were not affected by PSA antibodies. An ongoing phase III study will evaluate the systemic immune responses and correlation with clinical outcomes. (C) 2013 AACR.
C1 [Gulley, James L.; Madan, Ravi A.; Tsang, Kwong Y.; Jochems, Caroline; Marte, Jennifer L.; Farsaci, Benedetto; Tucker, Jo A.; Hodge, James W.; Heery, Christopher R.; Schlom, Jeffrey] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Liewehr, David J.; Steinberg, Seth M.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD USA.
RP Gulley, JL (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,13N208,MSC-1750, Bethesda, MD 20892 USA.
EM gulleyj@mail.nih.gov
RI Farsaci, Benedetto/L-9837-2014; Hodge, James/D-5518-2015; Gulley,
James/K-4139-2016
OI Farsaci, Benedetto/0000-0001-8275-2561; Hodge,
James/0000-0001-5282-3154; Gulley, James/0000-0002-6569-2912
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, NIH
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, NIH.
NR 41
TC 39
Z9 39
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2326-6066
EI 2326-6074
J9 CANCER IMMUNOL RES
JI Cancer Immunol. Res.
PD FEB
PY 2014
VL 2
IS 2
BP 133
EP 141
DI 10.1158/2326-6066.CIR-13-0108
PG 9
WC Oncology; Immunology
SC Oncology; Immunology
GA AM7FU
UT WOS:000340031200007
PM 24778277
ER
PT J
AU Compton, MT
Kelley, ME
Ionescu, DF
AF Compton, Michael T.
Kelley, Mary E.
Ionescu, Dawn F.
TI Subtyping first-episode non-affective psychosis using four early-course
features: potentially useful prognostic information at initial
presentation
SO EARLY INTERVENTION IN PSYCHIATRY
LA English
DT Article
DE age at onset; first-episode psychosis; premorbid functioning; prodrome;
schizophrenia
ID EARLY-ONSET SCHIZOPHRENIA; NEGATIVE SYNDROME SCALE; MINI-MENTAL-STATE;
AGE-OF-ONSET; PREMORBID ADJUSTMENT; UNTREATED PSYCHOSIS; 1ST EPISODE;
SYMPTOMS; PATTERNS; DURATION
AB Aim: Heterogeneity of symptoms, course and outcomes in primary psychotic disorders complicates prognosis, treatment and diverse aspects of research. This study aimed to identify interpretable subtypes of first-episode non-affective psychosis based on four early-course features (premorbid academic functioning, premorbid social functioning, duration of the prodrome and age at onset of psychosis).
Methods: Data from 200 well-characterized patients hospitalized in public-sector inpatient units for first-episode non-affective psychosis were used in latent profile analyses. Derived subtypes were then compared along a number of clinical dimensions using analyses of variance.
Results: Using four early-course features, three classes were derived. A good premorbid/short prodrome subtype was characterized by a lower severity of positive symptoms, better social/occupational/global functioning, and a shorter duration of untreated psychosis; a poor premorbid/early onset subtype demonstrated greater negative and preoccupation symptoms, as well as greater psychosocial problems; and a long prodrome/late onset subtype was characterized by greater dysphoric symptoms.
Conclusions: Findings indicate a need for further research with first-episode samples on the utility of subtyping based on early-course (premorbid, prodromal and onset-related) characteristics. Such efforts could enhance the parsing of heterogeneity, thereby advancing clinical practice and research.
C1 [Compton, Michael T.] George Washington Univ, Sch Med & Hlth Sci, Dept Psychiat & Behav Sci, Washington, DC 20037 USA.
[Kelley, Mary E.] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA.
[Ionescu, Dawn F.] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA.
RP Compton, MT (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Psychiat & Behav Sci, 2120 L St,Suite 600 NW, Washington, DC 20037 USA.
EM mcompton@mfa.gwu.edu
RI Ionescu, Dawn/K-5675-2015
FU National Institute of Mental Health [K23 MH067589, R01 MH081011]
FX This research was supported by grants K23 MH067589 and R01 MH081011 to
the first author from the National Institute of Mental Health.
NR 70
TC 1
Z9 1
U1 2
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1751-7885
EI 1751-7893
J9 EARLY INTERV PSYCHIA
JI Early Interv. Psychiatry
PD FEB
PY 2014
VL 8
IS 1
BP 50
EP 58
DI 10.1111/eip.12026
PG 9
WC Psychiatry
SC Psychiatry
GA AM4CD
UT WOS:000339798600007
PM 23343467
ER
PT J
AU Mete, O
Tischler, AS
de Krijger, R
McNicol, AM
Eisenhofer, G
Pacak, K
Ezzat, S
Asa, SL
AF Mete, Ozgur
Tischler, Arthur S.
de Krijger, Ronald
McNicol, Anne Marie
Eisenhofer, Graeme
Pacak, Karel
Ezzat, Shereen
Asa, Sylvia L.
TI Protocol for the Examination of Specimens From Patients With
Pheochromocytomas and Extra-Adrenal Paragangliomas
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Article
ID NEUROENDOCRINE TUMORS; GERMLINE MUTATIONS; GENE-MUTATIONS; SDHB;
LOCALIZATION; DIAGNOSIS; PEPTIDES; FEATURES; PROGRESS; HEAD
AB During the last decade there have been revolutionary breakthroughs in understanding the biology of pheochromocytomas and extra-adrenal paragangliomas. Discoveries of new susceptibility genes and genotype-phenotype correlations have led to the realization that appropriate patient care requires a complete integration of clinical, genetic, biochemical, imaging, and pathology findings. Clinical practice has in many cases not kept pace with the rate of discovery, underscoring a need for updated procedures for evaluation of patient specimens and reporting of data. We therefore propose a new synoptic reporting approach for pheochromocytomas and extra-adrenal paragangliomas that will provide clear and uniform information to pathologists and clinicians, in order to advance the diagnosis of these neoplasms and optimize patient care.
C1 [Mete, Ozgur; Asa, Sylvia L.] Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2C4, Canada.
[Ezzat, Shereen] Univ Hlth Network, Dept Med, Toronto, ON M5G 2C4, Canada.
[Tischler, Arthur S.] Tufts Med Ctr, Dept Pathol, Boston, MA USA.
[de Krijger, Ronald] Erasmus MC Univ, Med Ctr, Dept Pathol, Rotterdam, Netherlands.
[McNicol, Anne Marie] Univ Queensland, Royal Brisbane & Womens Hosp, Clin Res Ctr, Dept Mol & Cellular Pathol, Brisbane, Qld, Australia.
[Eisenhofer, Graeme] Univ Dresden, Inst Clin Chem & Lab Med, Dresden, Germany.
[Eisenhofer, Graeme] Univ Dresden, Dept Med 3, Dresden, Germany.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Hlth, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
RP Mete, O (reprint author), Univ Hlth Network, Dept Pathol, 200 Elizabeth St,11th Floor, Toronto, ON M5G 2C4, Canada.
EM ozgur.mete2@uhn.ca
FU Intramural NIH HHS [ZIA HD008735-12]
NR 49
TC 20
Z9 20
U1 0
U2 1
PU COLL AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
EI 1543-2165
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD FEB
PY 2014
VL 138
IS 2
BP 182
EP 188
DI 10.5858/arpa.2012-0551-OA
PG 7
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA AM0QF
UT WOS:000339550000011
PM 24476517
ER
PT J
AU Wolff, AC
Hammond, MEH
Hicks, DG
Dowsett, M
McShane, LM
Allison, KH
Allred, DC
Bartlett, JMS
Bilous, M
Fitzgibbons, P
Hanna, W
Jenkins, RB
Mangu, PB
Paik, S
Perez, EA
Press, MF
Spears, PA
Vance, GH
Viale, G
Hayes, DF
AF Wolff, Antonio C.
Hammond, M. Elizabeth H.
Hicks, David G.
Dowsett, Mitch
McShane, Lisa M.
Allison, Kimberly H.
Allred, Donald C.
Bartlett, John M. S.
Bilous, Michael
Fitzgibbons, Patrick
Hanna, Wedad
Jenkins, Robert B.
Mangu, Pamela B.
Paik, Soonmyung
Perez, Edith A.
Press, Michael F.
Spears, Patricia A.
Vance, Gail H.
Viale, Giuseppe
Hayes, Daniel F.
TI Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in
Breast Cancer American Society of Clinical Oncology/College of American
Pathologists Clinical Practice Guideline Update
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Article
ID IN-SITU HYBRIDIZATION; HER2 GENE AMPLIFICATION; RABBIT
MONOCLONAL-ANTIBODY; CORE NEEDLE-BIOPSY; TIME RT-PCR; ASCO/CAP
HER2-POSITIVITY CRITERIA; ADJUVANT TRASTUZUMAB BENEFIT; TISSUE
MICROARRAY TECHNOLOGY; POLYMERASE CHAIN-REACTION; ESTROGEN-RECEPTOR
AB Purpose. To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer.
Methods. ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing.
Results. The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations.
Recommendations. The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to >10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing.
C1 [Wolff, Antonio C.] Johns Hopkins Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[McShane, Lisa M.] NCI, Bethesda, MD 20892 USA.
[Hammond, M. Elizabeth H.] Univ Utah, Sch Med & Intermt Healthcare, Salt Lake City, UT USA.
[Hicks, David G.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
[Dowsett, Mitch] Royal Marsden Hosp, London SW3 6JJ, England.
[Allison, Kimberly H.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
[Fitzgibbons, Patrick] St Jude Med Ctr, Fullerton, CA USA.
[Press, Michael F.] Univ So Calif, Los Angeles, CA USA.
[Allred, Donald C.] Washington Univ, Sch Med, St Louis, MO USA.
[Bartlett, John M. S.] Ontario Inst Canc Res, Toronto, ON, Canada.
[Hanna, Wedad] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
[Bilous, Michael] Univ Western Sydney & Healthscope Pathol, Sydney, NSW, Australia.
[Jenkins, Robert B.] Mayo Clin, Rochester, MN USA.
[Mangu, Pamela B.] Amer Soc Clin Oncol, Alexandria, VA USA.
[Paik, Soonmyung] Natl Surg Adjuvant Breast & Bowel Project, Pitsburgh, PA USA.
[Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA.
[Spears, Patricia A.] N Carolina State Univ, Raleigh, NC 27695 USA.
[Vance, Gail H.] Indiana Univ, Med Ctr, Indianapolis, IN USA.
[Viale, Giuseppe] Univ Milan, European Inst Oncol, Milan, Italy.
[Hayes, Daniel F.] Univ Michigan, Comprehens Canc Care Ctr, Ann Arbor, MI 48109 USA.
RP Wolff, AC (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA.
EM guidelines@asco.org
OI Fitzgibbons, Patrick/0000-0002-2998-6913; Wolff,
Antonio/0000-0003-3734-1063
FU Roche UK; Roche; Abbott
FX Other Remuneration: John M. S. Bartlett, Roche UK; Wedad Hanna, Roche;
Robert B. Jenkins, Abbott.
NR 155
TC 198
Z9 211
U1 4
U2 24
PU COLL AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
EI 1543-2165
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD FEB
PY 2014
VL 138
IS 2
BP 241
EP 256
DI 10.5858/arpa.2013-0953-SA
PG 16
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA AM0QF
UT WOS:000339550000019
PM 24099077
ER
PT J
AU Mash, C
Bornstein, MH
Banerjee, A
AF Mash, Clay
Bornstein, Marc H.
Banerjee, Abhilasha
TI Development of Object Control in the First Year: Emerging Category
Discrimination and Generalization in Infants' Adaptive Selection of
Action
SO DEVELOPMENTAL PSYCHOLOGY
LA English
DT Article
DE action selection; categorization; infancy; motor control; generalization
ID INDUCTIVE GENERALIZATION; CATEGORIZATION; INFORMATION; IDENTIFICATION;
REPRESENTATION; INDIVIDUATION; COORDINATION; MANIPULATION; PERCEPTION;
TRANSITION
AB This research examined the development of adaptive generalization in infants' object-directed actions. Infants ages 9 and 12 months participated in an object manipulation task with stimulus objects from 2 categories that differed in shape and weight and that bore a consistent shape or weight correspondence. Weight differences between categories affected infants' actions required to handle objects effectively. Infants manually explored objects from both categories and then were tested for their selection of different actions between categories and their generalization to novel exemplars within categories. Nine-month-olds provided no evidence of category differentiation and generalization; however, 12-month-olds adapted their actions selectively for objects of each category and generalized those actions to novel objects within categories. A second sample of 9-month-olds who were examined in a simplified task with just one object per weight level successfully adapted their actions by weight. Together, the findings provide evidence for the development of selection and generalization in manipulative action across the second half of the first year of life.
C1 [Mash, Clay; Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Child & Family Res, NIH, Bethesda, MD USA.
[Banerjee, Abhilasha] Georgetown Univ, Dept Biol, Washington, DC 20057 USA.
RP Mash, C (reprint author), NICHD, 6705 Rockledge Dr, Bethesda, MD 20892 USA.
EM mashc@mail.nih.gov
FU Intramural NIH HHS [ZIA HD001119-26]
NR 50
TC 1
Z9 1
U1 1
U2 3
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0012-1649
EI 1939-0599
J9 DEV PSYCHOL
JI Dev. Psychol.
PD FEB
PY 2014
VL 50
IS 2
BP 325
EP 335
DI 10.1037/a0033234
PG 11
WC Psychology, Developmental
SC Psychology
GA AM5EF
UT WOS:000339878300001
PM 23772823
ER
PT J
AU Knebel, AR
Sharpe, VA
Danis, M
Toomey, LM
Knickerbocker, DK
AF Knebel, Ann R.
Sharpe, Virginia A.
Danis, Marion
Toomey, Lauren M.
Knickerbocker, Deborah K.
TI Informing the Gestalt: An Ethical Framework for Allocating Scarce
Federal Public Health and Medical Resources to States During Disasters
SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS
LA English
DT Article
DE ethical issues; politics; state/local issues
ID ISSUES
AB During catastrophic disasters, government leaders must decide how to efficiently and effectively allocate scarce public health and medical resources. The literature about triage decision making at the individual patient level is substantial, and the National Response Framework provides guidance about the distribution of responsibilities between federal and state governments. However, little has been written about the decision-making process of federal leaders in disaster situations when resources are not sufficient to meet the needs of several states simultaneously. We offer an ethical framework and logic model for decision making in such circumstances. We adapted medical triage and the federalism principle to the decision-making process for allocating scarce federal public health and medical resources. We believe that the logic model provides a values-based framework that can inform the gestalt during the iterative decision process used by federal leaders as they allocate scarce resources to states during catastrophic disasters.
C1 [Knebel, Ann R.] NINR, NIH, Bethesda, MD 20892 USA.
[Danis, Marion] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
[Sharpe, Virginia A.] Vet Hlth Adm, Natl Ctr Eth Hlth Care, Washington, DC USA.
[Toomey, Lauren M.; Knickerbocker, Deborah K.] US Dept HHS, Off Assistant Secretary Preparedness & Response, Off Emergency Management, Washington, DC 20201 USA.
RP Knebel, AR (reprint author), NINR, NIH, 31 Ctr Dr,Bldg 31,Rm 5B05, Bethesda, MD 20892 USA.
EM ann.knebel@hhs.gov
NR 33
TC 1
Z9 1
U1 5
U2 13
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1935-7893
EI 1938-744X
J9 DISASTER MED PUBLIC
JI Dis. Med. Public Health Prep.
PD FEB
PY 2014
VL 8
IS 1
BP 79
EP 88
DI 10.1017/dmp.2014.9
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AL3XG
UT WOS:000339064300012
PM 24612854
ER
PT J
AU Stender, SR
Brown, RJ
Cochran, E
Baez, E
Gumus, P
Lacassie, Y
AF Stender, S. R.
Brown, R. J.
Cochran, E.
Baez, E.
Gumus, P.
Lacassie, Y.
TI LEPTIN DEFICIENCY PRESENTING AS NEW ONSET DIABETES MELLITUS IN AN 11
YEAR OLD BOY WITH PROGEROID APPEARANCE
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
C1 [Stender, S. R.; Baez, E.; Gumus, P.; Lacassie, Y.] LSU Hlth Sci Ctr, New Orleans, LA USA.
[Brown, R. J.; Cochran, E.] NIDDK, NIH, DEOB, 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 1081-5589
EI 1708-8267
J9 J INVEST MED
JI J. Invest. Med.
PD FEB
PY 2014
VL 62
IS 2
MA 506
BP 558
EP 559
PG 2
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA AL3SH
UT WOS:000339048800516
ER
PT J
AU Fulop, T
Tapolyai, M
Zsom, L
Hickson, DA
Lirette, S
Flessner, MF
Griswold, M
AF Fueloep, T.
Tapolyai, M.
Zsom, L.
Hickson, D. A.
Lirette, S.
Flessner, M. F.
Griswold, M.
TI URINARY ELCTROLYTE EXCRETION AND SERUM POTASSIUM AMONG
AFRICAN-AMERICANS; THE JACKSON HEART STUDY
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
C1 [Fueloep, T.; Zsom, L.; Hickson, D. A.; Lirette, S.; Griswold, M.] Univ Mississippi Med Ctr, Jackson, MS USA.
[Tapolyai, M.] Univ S Carolina, WJB Dorn VA Med Ctr, Columbia, SC 29208 USA.
[Hickson, D. A.; Griswold, M.] Jackson Heart Study, Jackson, MS USA.
[Hickson, D. A.] Jackson State Univ, Jackson, MS USA.
[Flessner, M. F.] NIDDK, 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 1081-5589
EI 1708-8267
J9 J INVEST MED
JI J. Invest. Med.
PD FEB
PY 2014
VL 62
IS 2
MA 560
BP 574
EP 575
PG 2
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA AL3SH
UT WOS:000339048800569
ER
PT J
AU Uittenbogaard, AM
Myers-Morales, T
Gorman, AA
Welsh, E
Wulff, C
Hinnebusch, BJ
Korhonen, TK
Straley, SC
AF Uittenbogaard, Annette M.
Myers-Morales, Tanya
Gorman, Amanda A.
Welsh, Erin
Wulff, Christine
Hinnebusch, B. Joseph
Korhonen, Timo K.
Straley, Susan C.
TI Temperature-dependence of yadBC phenotypes in Yersinia pestis
SO MICROBIOLOGY-SGM
LA English
DT Article
ID BORNE TRANSMISSION; SURFACE PROTEASE; OUTER-MEMBRANE; BUBONIC PLAGUE;
VIRULENCE; CELLS; GENES; PATHOGENESIS; NEUTROPHILS; EXPRESSION
AB YadB and YadC are putative trimeric autotransporters present only in the plague bacterium Yersinia pestis and its evolutionary predecessor, Yersinia pseudotuberculosis. Previously, yadBC was found to promote invasion of epithelioid cells by Y. pestis grown at 37 degrees C. In this study, we found that yadBC also promotes uptake of 37 degrees C-grown Y. pestis by mouse monocyte/macrophage cells. We tested whether yadBC might be required for lethality of the systemic stage of plague in which the bacteria would be pre-adapted to mammalian body temperature before colonizing internal organs and found no requirement for early colonization or growth over 3 days. We tested the hypothesis that YadB and YadC function on ambient temperature-grown Y. pestis in the flea vector or soon after infection of the dermis in bubonic plague. We found that yadBC did not promote uptake by monocyte/macrophage cells if the bacteria were grown at 28 degrees C, nor was there a role of yadBC in colonization of fleas by Y. pestis grown at 21 C. However, the presence of yadBC did promote recoverability of the bacteria from infected skin for 28 degrees C-grown Y. pestis. Furthermore, the gene for the proinflammatory chemokine CXCL1 was upregulated in expression if the infecting Y. pestis lacked yadBC but not if yadBC was present. Also, yadBC was not required for recoverability if the bacteria were grown at 37 degrees C. These findings imply that thermally induced virulence properties dominate over effects of yadBC during plague but that yadBC has a unique function early after transmission of Y. pestis to skin.
C1 [Uittenbogaard, Annette M.; Myers-Morales, Tanya; Gorman, Amanda A.; Welsh, Erin; Wulff, Christine; Straley, Susan C.] Univ Kentucky, Dept Microbiol Immunol & Mol Genet, Lexington, KY 40536 USA.
[Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Korhonen, Timo K.] Univ Helsinki, Dept Biosci, Div Gen Microbiol, Helsinki, Finland.
RP Straley, SC (reprint author), Univ Kentucky, Dept Microbiol Immunol & Mol Genet, Lexington, KY 40536 USA.
EM scstraO1@uky.edu
FU PHS (NIAID) ARRA [R21 AI083861]; PHS (NIAID) [R01 AI48491]; University
of Kentucky Faculty Research Support grant
FX This study was supported by PHS (NIAID) ARRA grant R21 AI083861, PHS
(NIAID) grant R01 AI48491, and by a University of Kentucky Faculty
Research Support grant, all to S. C. S. The authors acknowledge
Christopher Jester (Department of Biology, University of Kentucky) for
measuring survival of Y. pestis in PMNs. None of the authors has any
conflict of interest that would affect this work.
NR 34
TC 1
Z9 1
U1 3
U2 8
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 1350-0872
J9 MICROBIOL-SGM
JI Microbiology-(UK)
PD FEB
PY 2014
VL 160
BP 396
EP 405
DI 10.1099/mic.0.073205-0
PN 2
PG 10
WC Microbiology
SC Microbiology
GA AK7IX
UT WOS:000338603100015
PM 24222617
ER
PT J
AU Bhatnagar, S
Hoberman, A
Kearney, DH
Shaikh, N
Moxey-Mims, MM
Chesney, RW
Carpenter, MA
Greenfield, SP
Keren, R
Mattoo, TK
Mathews, R
Gravens-Mueller, L
Ivanova, A
AF Bhatnagar, Sonika
Hoberman, Alejandro
Kearney, Diana H.
Shaikh, Nader
Moxey-Mims, Marva M.
Chesney, Russell W.
Carpenter, Myra A.
Greenfield, Saul P.
Keren, Ron
Mattoo, Tej K.
Mathews, Ranjiv
Gravens-Mueller, Lisa
Ivanova, Anastasia
TI Development and Impact of an Intervention to Boost Recruitment in a
Multicenter Pediatric Randomized Clinical Trial
SO CLINICAL PEDIATRICS
LA English
DT Article
DE recruitment; intervention; clinical trial
ID RETENTION
AB Objectives. Our primary objective was to develop and evaluate an intervention to increase recruitment in a multicenter pediatric randomized clinical trial (RCT). Our secondary objective was to assess the impact beyond 120 days. Methods. The study was conducted at 17 academic centers participating in a pediatric RCT. The intervention consisted of utilizing a recruitment assessment tool at a site visit or teleconference with key site personnel. Results. We found a significant increase in the number of individuals enrolled for all 17 sites at 120 days postintervention (mean = 1.12 per site; median = 1 per site; 95% confidence interval = 1-2; P = .04). No significant differences were apparent beyond the first 120 days postintervention. Conclusions. Successful recruitment in RCTs is essential to the quality, generalizability, and cost-effectiveness of clinical research. Implementation of this recruitment intervention may effectively increase recruitment in RCTs. Beyond the first 120 days postintervention, repeated interventions may be required. What is new? Despite general and pediatric-specific challenges to recruitment in RCTs, a paucity of evidence exists on effective recruitment strategies or assessment tools to reliably enhance recruitment. We developed a recruitment intervention for use in RCTs that enables clinical researchers to enhance recruitment.
C1 [Bhatnagar, Sonika; Hoberman, Alejandro; Kearney, Diana H.; Shaikh, Nader] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Moxey-Mims, Marva M.] NIDDK, NIH, Bethesda, MD USA.
[Chesney, Russell W.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Carpenter, Myra A.; Gravens-Mueller, Lisa; Ivanova, Anastasia] Univ N Carolina, Chapel Hill, NC USA.
[Greenfield, Saul P.] Women & Childrens Hosp Buffalo, Buffalo, NY USA.
[Keren, Ron] Univ Penn, Philadelphia, PA 19104 USA.
[Mattoo, Tej K.] Childrens Hosp Michigan, Detroit, MI 48201 USA.
[Mathews, Ranjiv] Johns Hopkins Sch Med, Baltimore, MD USA.
RP Bhatnagar, S (reprint author), UPMC, Childrens Hosp Pittsburgh, Div Gen Acad Pediat, CHOB, 4401 Penn Ave,3 Floor, Pittsburgh, PA 15224 USA.
EM sonika.bhatnagar@chp.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, Department of Health and Human Services
[U01 DK074059, U01 DK074053, U01 DK074082, U01 DK074064, U01 DK074062,
U01 DK074063]; Children's Hospital of Philadelphia Clinical and
Translational Science Award from the National Center for Research
Resources at the National Center for Advancing Translational Sciences,
National Institutes of Health [UL1TR000003]
FX The authors thank the Randomized Intervention for Children with
Vesicoureteral Reflux (RIVUR) participants, their families, and the
participating clinicians, investigators, and staff for making this
research possible. The RIVUR trial was supported by cooperative
agreements U01 DK074059 (Carpenter), U01 DK074053 (Hoberman), U01
DK074082 (Mathews), U01 DK074064 (Keren), U01 DK074062 (Mattoo), and U01
DK074063 (Greenfield) from the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health, Department
of Health and Human Services. The trial was also supported by the
Children's Hospital of Philadelphia Clinical and Translational Science
Award (UL1TR000003) from the National Center for Research Resources, now
at the National Center for Advancing Translational Sciences, National
Institutes of Health. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Institute of Diabetes and Digestive and Kidney Diseases or the
National Institutes of Health. The RIVUR Web site is located at
http://www.cscc.unc.edu/rivur/.
NR 14
TC 4
Z9 4
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0009-9228
EI 1938-2707
J9 CLIN PEDIATR
JI Clin. Pediatr.
PD FEB
PY 2014
VL 53
IS 2
BP 151
EP 157
DI 10.1177/0009922813506961
PG 7
WC Pediatrics
SC Pediatrics
GA AJ8MZ
UT WOS:000337960700008
PM 24151147
ER
PT J
AU Schmitz, R
Ceribelli, M
Pittaluga, S
Wright, G
Staudt, LM
AF Schmitz, Roland
Ceribelli, Michele
Pittaluga, Stefania
Wright, George
Staudt, Louis M.
TI Oncogenic Mechanisms in Burkitt Lymphoma
SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
LA English
DT Article
ID EPSTEIN-BARR-VIRUS; B-CELL LYMPHOMAS; C-MYC; GERMINAL CENTER; BET
BROMODOMAINS; AFRICAN CHILDREN; TRANSGENIC MICE; IMMUNE-SYSTEM; CYCLIN
D3; EXPRESSION
AB Burkitt lymphoma is a germinal center B-cell-derived cancer that was instrumental in the identification of MYC as an important human oncogene more than three decades ago. Recently, new genomics technologies have uncovered several additional oncogenic mechanisms that cooperate with MYC to create this highly aggressive cancer. The transcription factor TCF-3 is central to Burkitt lymphoma pathogenesis. TCF-3 is rendered constitutively active in Burkitt lymphoma by two related mechanisms: (1) somatic mutations that inactivate its negative regulator ID3, and (2) somatic mutations in TCF-3 that block the ability of ID3 to bind and interfere with its activity as a transcription factor. TCF-3 is also a master regulator of normal germinal center B-cell differentiation. Within the germinal center, TCF-3 up-regulates genes that are characteristically expressed in the rapidly dividing centroblasts, the putative cell of origin for Burkitt lymphoma, while repressing genes expressed in the less proliferative centrocytes. TCF-3 promotes antigen-independent (tonic) B-cell-receptor signaling in Burkitt lymphoma by transactivating immunoglobulin heavy-and light-chain genes while repressing PTPN6, which encodes the phosphatase SHP-1, a negative regulator of B-cell- receptor signaling. Tonic B-cell-receptor signaling sustains Burkitt lymphoma survival by engaging the PI3 kinase pathway. In addition, TCF-3 promotes cell-cycle progression by transactivating CCND3, encoding a D-type cyclin that regulates the G(1)-S phase transition. Additionally, CCND3 accumulates oncogenic mutations that stabilize cyclin D3 protein expression and drive proliferation. These new insights into Burkitt lymphoma pathogenesis suggest new therapeutic strategies, which are sorely needed in developing regions of the world where this cancer is endemic.
C1 [Schmitz, Roland; Ceribelli, Michele; Staudt, Louis M.] NCI, Lymphoid Malignancies Branch, NIH, Bethesda, MD 20892 USA.
[Pittaluga, Stefania] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wright, George] NCI, Biometr Res Branch, DCTD, NIH, Bethesda, MD 20892 USA.
RP Staudt, LM (reprint author), NCI, Lymphoid Malignancies Branch, NIH, Bethesda, MD 20892 USA.
EM lstaudt@mail.nih.gov
FU Mildred Scheel Stiftung fur Krebsforschung (Deutsche Krebshilfe)
FX We thank Moez Dawood for helpful discussion. R.S. is supported by the
Dr. Mildred Scheel Stiftung fur Krebsforschung (Deutsche Krebshilfe).
NR 61
TC 21
Z9 23
U1 1
U2 6
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 2157-1422
J9 CSH PERSPECT MED
JI Cold Spring Harb. Perspect. Med.
PD FEB
PY 2014
VL 4
IS 2
AR a014282
DI 10.1101/cshperspect.a014282
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AJ9HI
UT WOS:000338018500003
ER
PT J
AU Kim, SH
Xiao, S
Paldurai, A
Collins, PL
Samal, SK
AF Kim, Shin-Hee
Xiao, Sa
Paldurai, Anandan
Collins, Peter L.
Samal, Siba K.
TI Role of C596 in the C-terminal extension of the
haemagglutinin-neuraminidase protein in replication and pathogenicity of
a highly virulent Indonesian strain of Newcastle disease virus
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID MEMBRANE GLYCOPROTEIN PRECURSORS; PROTEOLYTIC CLEAVAGE; FUSION PROTEIN;
ACTIVATION; SITE
AB We modified the haemagglutinin neuraminidase (HN) glycoprotein of the virulent Newcastle disease virus (NDV) strain Banjarmasin/010/10 (Ban/010) by adding C-terminal extensions similar to those found in certain avirulent NDV strains. Extension of the 571 aa wt Ban/010 HN protein to 577 and 616 aa by removal of one or two translational stop codons moderately reduced HN function and viral pathogenicity in 1-day-old and 3-week-old chickens. Substantially greater reductions were achieved by altering the 616 aa form by introducing a R596C mutation or by replacing the C-terminal extension with that of avirulent strain Ulster, which naturally contains the amino acid 596C. These results showed that extension of the C terminus of HN reduces NDV pathogenicity, and that this effect is substantially increased by the presence of 596C. These results indicate that this attenuating mechanism in avirulent strains such as Ulster can be applied directly to a highly virulent strain recently in circulation.
C1 [Kim, Shin-Hee; Xiao, Sa; Paldurai, Anandan; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
EM ssamal@umd.edu
FU NIAID [N01A060009]; NIAID, NIH, Intramural Research Program
FX We thank Daniel Rockemann, Girmay Gebreluul, Yonas Araya, Andrea
Ferrero-Perez and our laboratory members for excellent technical
assistance; and Dr Bernard Moss [National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH)] for
providing the vaccinia T7 recombinant virus and the pTM1 plasmid. This
research was supported by NIAID contract N01A060009 (85% support) and
the NIAID, NIH, Intramural Research Program (15% support). The views
expressed herein do not necessarily reflect the official policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial practices or organizations imply endorsement by the US
Government.
NR 16
TC 3
Z9 3
U1 1
U2 6
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
EI 1465-2099
J9 J GEN VIROL
JI J. Gen. Virol.
PD FEB
PY 2014
VL 95
BP 331
EP 336
DI 10.1099/vir.0.055285-0
PN 2
PG 6
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA AK1LU
UT WOS:000338177400009
PM 24197534
ER
PT J
AU Ludi, AB
Horton, DL
Li, Y
Mahapatra, M
King, DP
Knowles, NJ
Russell, CA
Paton, DJ
Wood, JLN
Smith, DJ
Hammond, JM
AF Ludi, A. B.
Horton, D. L.
Li, Y.
Mahapatra, M.
King, D. P.
Knowles, N. J.
Russell, C. A.
Paton, D. J.
Wood, J. L. N.
Smith, D. J.
Hammond, J. M.
TI Antigenic variation of foot-and-mouth disease virus serotype A
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID GENETIC EVOLUTION; MOLECULAR CHARACTERIZATION; MAXIMUM-LIKELIHOOD;
RECEPTOR; EPIDEMIOLOGY; ANTIBODIES; EUROPE; SITES
AB The current measures to control foot-and-mouth disease (FMD) include vaccination, movement control and slaughter of infected or susceptible animals. One of the difficulties in controlling FMD by vaccination arises due to the substantial diversity found among the seven serotypes of FMD virus (FMDV) and the strains within these serotypes. Therefore, vaccination using a single vaccine strain may not fully cross-protect against all strains within that serotype, and therefore selection of appropriate vaccines requires serological comparison of the field virus and potential vaccine viruses using relationship coefficients (r(1) values). Limitations of this approach are that antigenic relationships among field viruses are not addressed, as comparisons are only with potential vaccine virus. Furthermore, inherent variation among vaccine sera may impair reproducibility of one-way relationship scores. Here, we used antigenic cartography to quantify and visualize the antigenic relationships among FMD serotype A viruses, aiming to improve the understanding of FMDV antigenic evolution and the scope and reliability of vaccine matching. Our results suggest that predicting antigenic difference using genetic sequence alone or by geographical location is not currently reliable. We found co-circulating lineages in one region that were genetically similar but antigenically distinct. Nevertheless, by comparing antigenic distances measured from the antigenic maps with the full capsid (P1) sequence, we identified a specific amino acid substitution associated with an antigenic mismatch among field viruses and a commonly used prototype vaccine strain, A(22)/IRO124/64.
C1 [Ludi, A. B.; Li, Y.; Mahapatra, M.; King, D. P.; Knowles, N. J.; Paton, D. J.; Hammond, J. M.] Pirbright Inst, Pirbright GU24 0NF, Surrey, England.
[Ludi, A. B.; Horton, D. L.; Russell, C. A.; Wood, J. L. N.] Univ Cambridge, Dept Vet Med, Dis Dynam Unit, Cambridge CB3 0ES, England.
[Ludi, A. B.; Horton, D. L.; Smith, D. J.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
[Horton, D. L.] Anim Hlth & Vet Labs Agcy, Addlestone KT15 3NB, Surrey, England.
[Russell, C. A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Smith, D. J.] Erasmus MC, Dept Virol, NL-3000 CA Rotterdam, Netherlands.
[Russell, C. A.; Smith, D. J.] Univ Cambridge, WHO Collaborating Ctr Modelling Evolut & Control, Cambridge CB2 3EJ, England.
RP Ludi, AB (reprint author), ARS, Foreign Anim Dis Res Unit, USDA, Plum Isl Anim Dis Ctr, Greenport, NY 11944 USA.
EM Anna.Ludi@ars.usda.gov; drliy@yahoo.com
RI Horton, Daniel/D-9909-2011; APHA, Staff publications/E-6082-2010; Wood,
James/A-1626-2008; Institute, Pirbright/K-4476-2014;
OI Horton, Daniel/0000-0002-9126-2756; Wood, James/0000-0002-0258-3188;
King, Donald/0000-0002-6959-2708; Russell, Colin/0000-0002-2113-162X
FU Cambridge Infectious Diseases Consortium of the Veterinary Training and
Research Initiative (Defra grant) [VT0105]; Alborada Trust; Research and
Policy for Infectious Disease Dynamics program of the Science and
Technology Directorate, Department of Homeland Security and Fogarty
International Center; EU [228292, 223498]; Defra UK [SE2939]; NIH
Director's Pioneer Award [DP1-0D000490-0]; ANTIGONE [278976]; University
Research Fellowship from the Royal Society
FX Thanks are due to Bob Statham and the WRL/EURL FMD team for their advice
and expertise on the VNT and r1 values. A. B. L. was
supported by a fellowship from the Cambridge Infectious Diseases
Consortium of the Veterinary Training and Research Initiative (Defra
grant VT0105). J. L. N. W. is supported by the Alborada Trust and the
Research and Policy for Infectious Disease Dynamics program of the
Science and Technology Directorate, Department of Homeland Security and
Fogarty International Center. D. L. H. is partially supported by the
Cambridge Infectious Diseases Consortium Veterinary Training and
Research Initiative (Defra grant VT0105) and EU FP7 Research
Infrastructure Grant 'European Virus Archive (EVA)' (grant 228292). N.
J. K. was partially supported by a Defra UK grant (SE2939). D. J. S. and
C. A. R. acknowledge the support of EU FP7 grants EMPERIE (223498). C.
A. R. acknowledges the support of the NIH Director's Pioneer Award
DP1-0D000490-0 and D.J. S., C. A. R. and J. L. N. W. are also supported
by ANTIGONE (278976). C. A. R. was supported by a University Research
Fellowship from the Royal Society.
NR 46
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Z9 6
U1 0
U2 10
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
EI 1465-2099
J9 J GEN VIROL
JI J. Gen. Virol.
PD FEB
PY 2014
VL 95
BP 384
EP 392
DI 10.1099/vir.0.057521-0
PN 2
PG 9
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA AK1LU
UT WOS:000338177400014
PM 24187014
ER
PT J
AU Scialla, JJ
Xie, HL
Rahman, M
Anderson, AH
Isakova, T
Ojo, A
Zhang, XM
Nessel, L
Hamano, T
Grunwald, JE
Raj, DS
Yang, W
He, J
Lash, JP
Go, AS
Kusek, JW
Feldman, H
Wolf, M
AF Scialla, Julia J.
Xie, Huiliang
Rahman, Mahboob
Anderson, Amanda Hyre
Isakova, Tamara
Ojo, Akinlolu
Zhang, Xiaoming
Nessel, Lisa
Hamano, Takayuki
Grunwald, Juan E.
Raj, Dominic S.
Yang, Wei
He, Jiang
Lash, James P.
Go, Alan S.
Kusek, John W.
Feldman, Harold
Wolf, Myles
CA Chronic Renal Insufficiency Cohort
TI Fibroblast Growth Factor-23 and Cardiovascular Events in CKD
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; LEFT-VENTRICULAR HYPERTROPHY;
GLOMERULAR-FILTRATION-RATE; HIGHLY SENSITIVE ASSAY;
CORONARY-HEART-DISEASE; GENERAL-POPULATION; CARDIAC TROPONIN;
ATHEROSCLEROSIS RISK; PARATHYROID-HORMONE; RENAL-DISEASE
AB An elevated level of fibroblast growth factor-23 (FGF-23) is the earliest abnormality of mineral metabolism in CKD. High FGF-23 levels promote left ventricular hypertrophy but not coronary artery calcification. We used survival analysis to determine whether elevated FGF-23 is associated with greater risk of adjudicated congestive heart failure (CHF) and atherosclerotic events (myocardial infarction, stroke, and peripheral vascular disease) in a prospective cohort of 3860 participants with CKD stages 2-4 (baseline estimated GFR [eGFR], 44 +/- 15 ml/min per 1.73m(2)). During a median follow-up of 3.7 years, 360 participants were hospitalized for CHF (27 events/1000 person-years) and 287 had an atherosclerotic event (22 events/1000 person-years). After adjustment for demographic characteristics, kidney function, traditional cardiovascular risk factors, and medications, higher FGF-23 was independently associated with graded risk of CHF (hazard ratio [HR], 1.45 per doubling [95% confidence interval (CI), 1.28 to 1.65]; HR for highest versus lowest quartile, 2.98 [95% CI, 1.97 to 4.52]) and atherosclerotic events (HR per doubling, 1.24 [95% CI, 1.09 to 1.40]; HR for highest versus lowest quartile, 1.76 [95% CI, 1.20 to 2.59]). Elevated FGF-23 was associated more strongly with CHF than with atherosclerotic events (P=0.02), and uniformly was associated with greater risk of CHF events across subgroups stratified by eGFR, proteinuria, prior heart disease, diabetes, BP control, anemia, sodium intake, income, fat-free mass, left ventricular mass index, and ejection fraction. Thus, higher FGF-23 is independently associated with greater risk of cardiovascular events, particularly CHF, in patients with CKD stages 2-4.
C1 [Scialla, Julia J.; Xie, Huiliang; Isakova, Tamara; Wolf, Myles] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Rahman, Mahboob] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Anderson, Amanda Hyre; Zhang, Xiaoming; Nessel, Lisa; Hamano, Takayuki; Grunwald, Juan E.; Yang, Wei; Feldman, Harold] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Ojo, Akinlolu] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Raj, Dominic S.] George Washington Univ, Washington, DC USA.
[He, Jiang] Tulane Univ, New Orleans, LA 70118 USA.
[Lash, James P.] Univ Illinois, Chicago, IL USA.
[Go, Alan S.] Kaiser Permanente Div Res, Oakland, CA USA.
[Kusek, John W.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Wolf, M (reprint author), 633 N St Clair St, Chicago, IL 60611 USA.
EM myles.wolf@northwestern.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
[U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028,
U01DK060980, U01DK060963, U01DK060902]; University of Pennsylvania CTRC
CTSA [UL1 RR-024134]; Johns Hopkins University [UL1 RR-025005];
University of Maryland GCRC [M01 RR-16500]; Clinical and Translational
Science Collaborative of Cleveland; National Center for Advancing
Translational Sciences component of the National Institutes of Health
(NIH) [UL1TR000439]; NIH roadmap for Medical Research [UL1RR024986];
University of Illinois at Chicago [CTSAUL1RR029879]; Tulane University
Translational Research in Hypertension and Renal Biology [P30GM103337];
Kaiser NIH/NCRR UCSF-CTSI [UL1 RR-024131]; NIH [K23DK095949,
K01DK092353, R01DK073665, HL268200900040C, R01HL107241, R01DK076116,
R01DK081374, R01DK094796, K24DK093723, U54TR000255]; Michigan Institute
for Clinical and Health Research [UL1RR024986]
FX Funding for the CRIC study was obtained under a cooperative agreement
from the National Institute of Diabetes and Digestive and Kidney
Diseases (U01DK060990, U01DK060984, U01DK061022, U01DK061021,
U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition,
this work was supported in part by the University of Pennsylvania CTRC
CTSA UL1 RR-024134, Johns Hopkins University UL1 RR-025005, University
of Maryland GCRC M01 RR-16500, Clinical and Translational Science
Collaborative of Cleveland, UL1TR000439 from the National Center for
Advancing Translational Sciences component of the National Institutes of
Health (NIH) and NIH roadmap for Medical Research, Michigan Institute
for Clinical and Health Research UL1RR024986, University of Illinois at
Chicago CTSAUL1RR029879, Tulane University Translational Research in
Hypertension and Renal Biology P30GM103337, and Kaiser NIH/NCRR
UCSF-CTSI UL1 RR-024131. J.J.S. was supported by grant K23DK095949;
A.H.A. by K01DK092353; D.S.R. by R01DK073665, HL268200900040C, and
R01HL107241; and M.W. by R01DK076116, R01DK081374, R01DK094796,
K24DK093723, and U54TR000255, all from the NIH.
NR 47
TC 84
Z9 91
U1 5
U2 9
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD FEB 1
PY 2014
VL 25
IS 2
BP 349
EP 360
DI 10.1681/ASN.2013050465
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA AJ8QM
UT WOS:000337971700017
PM 24158986
ER
PT J
AU Shirota, H
Klinman, DM
AF Shirota, Hidekazu
Klinman, Dennis M.
TI Recent progress concerning CpG DNA and its use as a vaccine adjuvant
SO EXPERT REVIEW OF VACCINES
LA English
DT Review
DE allergy; cancer; CpG oligonucleotide; infection; Toll-like receptor;
vaccine adjuvant
ID PLASMACYTOID DENDRITIC CELLS; B SURFACE-ANTIGEN; TOLL-LIKE RECEPTORS;
DOUBLE-STRANDED-RNA; MUCOSAL IMMUNE-RESPONSES; NON-HODGKIN-LYMPHOMA;
IN-SITU VACCINATION; BLOOD-STAGE VACCINE; RANDOMIZED PHASE-II;
BACTERIAL-DNA
AB CpG Oligonucleotides (ODN) are immunomodulatory synthetic oligonucleotides designed to specifically agonize Toll-like receptor 9. Here, we review recent progress in understanding the mechanism of action of CpG ODN and provide an overview of human clinical trial results using CpG ODN to improve the vaccines for cancer, allergy and infectious disease.
C1 [Shirota, Hidekazu] Tohoku Univ, Dept Clin Oncol, Sendai, Miyagi 980, Japan.
[Klinman, Dennis M.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
RP Klinman, DM (reprint author), NCI, Canc & Inflammat Program, Bldg 567 Rm 205 NCI Frederick, Frederick, MD 21702 USA.
EM klinmand@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute
FX DM Klinman and members of his laboratory are inventors/co-inventors on a
number of patents pertaining to CpG ODN. All rights to these patents
have been assigned to the Federal Government. This work was supported by
the Intramural Research Program of the National Institutes of Health,
National Cancer Institute. The authors have no other relevant
affiliations or financial involvement with any organization or entity
with a financial interest in or financial conflict with the subject
matter or materials discussed in the manuscript apart from those
disclosed.
NR 163
TC 22
Z9 23
U1 2
U2 42
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1476-0584
EI 1744-8395
J9 EXPERT REV VACCINES
JI Expert Rev. Vaccines
PD FEB
PY 2014
VL 13
IS 2
BP 299
EP 312
DI 10.1586/14760584.2014.863715
PG 14
WC Immunology
SC Immunology
GA AJ8BB
UT WOS:000337926200013
PM 24308579
ER
PT J
AU Simon, SL
Linet, MS
AF Simon, Steven L.
Linet, Martha S.
TI RADIATION-EXPOSED POPULATIONS: WHO, WHY, AND HOW TO STUDY
SO HEALTH PHYSICS
LA English
DT Article
DE epidemiology; exposure, occupational; medical radiation; National
Council on Radiation Protection and Measurements
ID ATOMIC-BOMB SURVIVORS; CHILDHOOD LEUKEMIA INCIDENCE; NUCLEAR-WEAPONS
TESTS; LUNG-CANCER INCIDENCE; IONIZING-RADIATION; CHERNOBYL ACCIDENT;
DOSE ESTIMATION; THYROID-CANCER; BREAST-CANCER; INDOOR RADON
AB Everyone is exposed to natural and manmade ionizing radiation that can originate from sources in the environment and in medical and occupational settings. There is notable variation, however, among individuals and across populations in the types of sources of radiation and in the frequency, level, and duration of exposure. Adverse health effects associated with radiation exposure have been known for decades, and ionizing radiation exposure has been linkedwith a broad range of different types of cancer and benign neoplasms as well as birth defects, reproductive effects, and diseases of the circulatory, hematologic, and neurologic systems. Our present understanding of radiation-related health risks derives primarily from multidisciplinary health risk (epidemiologic) studies that provide the key information on radiation-associated health outcomes, quantify radiation-related disease risks, and enhance understanding of mechanisms of radiation-related disease pathogenesis. Such information is central to quantifying risks in relation to benefits; addressing public concerns, including societal and clinical needs in relation to radiation exposure; and providing the database needed for establishing recommendations for radiation protection. Because of the importance of determining risks compared to benefits for all situations where exposure to ionizing radiation might result, it is useful for planning new health risks studies to categorize exposed populations according to the sources and types of radiation. This paper describes a wide range of populations exposed to radiation and the motivation and key methodological criteria that drive the rationale and priority of studying such populations. Also, discussed are alternative methods for evaluating radiation-related health risks in these populations, with a major focus on epidemiologic approaches. This paper concludes with a short summary of major highlights from radiation epidemiologic research and important unanswered questions.
C1 [Simon, Steven L.; Linet, Martha S.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM ssimon@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health.
NR 75
TC 3
Z9 3
U1 1
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD FEB
PY 2014
VL 106
IS 2
BP 182
EP 195
DI 10.1097/HP.0000000000000006
PG 14
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA AJ2SO
UT WOS:000337512400007
PM 24378492
ER
PT J
AU Travis, LB
Ng, AK
Allan, JM
Pui, CH
Kennedy, AR
Xu, XG
Purdy, JA
Applegate, K
Yahalom, J
Constine, LS
Gilbert, ES
Boice, JD
AF Travis, Lois B.
Ng, Andrea K.
Allan, James M.
Pui, Ching-Hon
Kennedy, Ann R.
Xu, X. George
Purdy, James A.
Applegate, Kimberly
Yahalom, Joachim
Constine, Louis S.
Gilbert, Ethel S.
Boice, John D., Jr.
TI SECOND MALIGNANT NEOPLASMS AND CARDIOVASCULAR DISEASE FOLLOWING
RADIOTHERAPY
SO HEALTH PHYSICS
LA English
DT Article
DE cancer; health effects; medical radiation; National Council on Radiation
Protection and Measurements
ID RADIATION-THERAPY; TESTICULAR CANCER; BREAST-CANCER; HODGKINS-DISEASE;
RISK; CHEMOTHERAPY; CARCINOMA; SURVIVORS; ROLES; SUSCEPTIBILITY
AB Second malignant neoplasms (SMNs) and cardiovascular disease (CVD) are among the most serious and life-threatening late adverse effects experienced by the growing number of cancer survivors worldwide and are due in part to radiotherapy. The National Council on Radiation Protection and Measurements (NCRP) convened an expert scientific committee to critically and comprehensively review associations between radiotherapy and SMNs and CVD, taking into account radiobiology; genomics; treatment (i.e., radiotherapy with or without chemotherapy and other therapies); type of radiation; and quantitative considerations (i.e., dose-response relationships). Major conclusions of the NCRP include: (1) the relevance of older technologies for current risk assessment when organ-specific absorbed dose and the appropriate relative biological effectiveness are taken into account and (2) the identification of critical research needs with regard to newer radiation modalities, dose-response relationships, and genetic susceptibility. Recommendation for research priorities and infrastructural requirements include (1) long-term large-scale follow-up of extant cancer survivors and prospectively treated patients to characterize risks of SMNs and CVD in terms of radiation dose and type; (2) biological sample collection to integrate epidemiological studies with molecular and genetic evaluations; (3) investigation of interactions between radiotherapy and other potential confounding factors, such as age, sex, race, tobacco and alcohol use, dietary intake, energy balance, and other cofactors, as well as genetic susceptibility; (4) focusing on adolescent and young adult cancer survivors, given the sparse research in this population; and (5) construction of comprehensive risk prediction models for SMNs and CVD to permit the development of follow-up guidelines and prevention and intervention strategies.
C1 [Travis, Lois B.; Constine, Louis S.] Univ Rochester, Med Ctr, Rubin Ctr Canc Survivorship, Rochester, NY 14642 USA.
[Travis, Lois B.; Constine, Louis S.] Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA.
[Ng, Andrea K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA.
[Ng, Andrea K.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Allan, James M.] Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Pui, Ching-Hon] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
[Pui, Ching-Hon] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Kennedy, Ann R.] Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA.
[Xu, X. George] Rensselaer Polytech Inst, Nucl Engn & Engn Phys Program, Troy, NY USA.
[Purdy, James A.] Univ Calif Davis, Dept Radiat Oncol, Davis, CA 95616 USA.
[Applegate, Kimberly] Emory Univ, Dept Radiol, Atlanta, GA 30322 USA.
[Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA.
[Gilbert, Ethel S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Boice, John D., Jr.] Natl Council Radiat Protect & Measurements, Bethesda, MD USA.
[Boice, John D., Jr.] Vanderbilt Univ, Dept Med, Nashville, TN USA.
RP Travis, LB (reprint author), Univ Rochester, Med Ctr, Rubin Ctr Canc Survivorship, 265 Crittenden Blvd,CU 420318, Rochester, NY 14642 USA.
EM Lois_Travis@URMC.Rochester.edu
FU National Institutes of Health [CA21765]; American Lebanese Syrian
Associated Charities; University of Rochester Medical Center
FX Supported in part by grant CA21765 from the National Institutes of
Health, the American Lebanese Syrian Associated Charities (Ching-Hon
Pui), and the University of Rochester Medical Center (Lois B. Travis).
NR 26
TC 9
Z9 10
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD FEB
PY 2014
VL 106
IS 2
BP 229
EP 246
DI 10.1097/HP.0000000000000013
PG 18
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA AJ2SO
UT WOS:000337512400013
PM 24378498
ER
PT J
AU Bouville, A
Kryuchkov, V
AF Bouville, Andre
Kryuchkov, Victor
TI INCREASED OCCUPATIONAL RADIATION DOSES: NUCLEAR FUEL CYCLE
SO HEALTH PHYSICS
LA English
DT Article
DE National Council on Radiation Protection and Measurements; accidents,
nuclear; Chernobyl; occupational safety
ID CHERNOBYL CLEANUP WORKERS; UKRAINIAN-AMERICAN; THYROID-CANCER;
DOSIMETRY; RISK; LIQUIDATORS; ACCIDENT; RECONSTRUCTION; DISORDERS;
LEUKEMIA
AB The increased occupational doses resulting from the Chernobyl nuclear reactor accident that occurred in Ukraine in April 1986, the reactor accident of Fukushima that took place in Japan in March 2011, and the early operations of the Mayak Production Association in Russia in the 1940s and 1950s are presented and discussed. For comparison purposes, the occupational doses due to the other two major reactor accidents (Windscale in the United Kingdomin 1957 and Three Mile Island in the United States in 1979) and to the main plutonium-producing facility in the United States (Hanford Works) are also covered but in less detail. Both for the Chernobyl nuclear reactor accident and the routine operations at Mayak, the considerable efforts made to reconstruct individual doses from external irradiation to a large number of workers revealed that the recorded doses had been overestimated by a factor of about two.
C1 [Bouville, Andre] NCI, Rockville, MD 20850 USA.
[Kryuchkov, Victor] Fed Med Biol Agcy, Burnasyan Fed Med Biophys Ctr, Moscow 123182, Russia.
RP Bouville, A (reprint author), 9609 Med Dr,Room 7E590,MSC 9778, Rockville, MD 20850 USA.
EM andre.bouville@nih.gov
NR 44
TC 3
Z9 3
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD FEB
PY 2014
VL 106
IS 2
BP 259
EP 271
DI 10.1097/HP.0000000000000066
PG 13
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA AJ2SO
UT WOS:000337512400016
PM 24378501
ER
PT J
AU Hatch, M
AF Hatch, Maureen
TI NUCLEAR REACTOR ACCIDENTS: EXPOSURES AND HEALTH EFFECTS AMONG MEMBERS OF
THE PUBLIC
SO HEALTH PHYSICS
LA English
DT Editorial Material
ID THYROID-CANCER; MILE-ISLAND; I-131; FUKUSHIMA; MORTALITY; DISEASES;
PLANT
C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Hatch, M (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM hatchm@mail.nih.gov
NR 19
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD FEB
PY 2014
VL 106
IS 2
BP 307
EP 308
DI 10.1097/HP.0000000000000014
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA AJ2SO
UT WOS:000337512400022
PM 24378507
ER
PT J
AU Pai, VM
Rodgers, M
Conroy, R
Luo, J
Zhou, RX
Seto, B
AF Pai, Vinay M.
Rodgers, Mary
Conroy, Richard
Luo, James
Zhou, Ruixia
Seto, Belinda
TI Workshop on using natural language processing applications for enhancing
clinical decision making: an executive summary
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID RADIOLOGY REPORTS; SUPPORT SYSTEMS; INFORMATION; KNOWLEDGE
AB In April 2012, the National Institutes of Health organized a two-day workshop entitled 'Natural Language Processing: State of the Art, Future Directions and Applications for Enhancing Clinical Decision-Making' (NLP-CDS). This report is a summary of the discussions during the second day of the workshop. Collectively, the workshop presenters and participants emphasized the need for unstructured clinical notes to be included in the decision making workflow and the need for individualized longitudinal data tracking. The workshop also discussed the need to: (1) combine evidence-based literature and patient records with machine-learning and prediction models; (2) provide trusted and reproducible clinical advice; (3) prioritize evidence and test results; and (4) engage healthcare professionals, caregivers, and patients. The overall consensus of the NLP-CDS workshop was that there are promising opportunities for NLP and CDS to deliver cognitive support for healthcare professionals, caregivers, and patients.
C1 [Pai, Vinay M.; Rodgers, Mary; Conroy, Richard; Luo, James; Zhou, Ruixia; Seto, Belinda] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
[Rodgers, Mary] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
RP Pai, VM (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, 6707 Democracy Blvd,Ste 200, Bethesda, MD 20892 USA.
EM paiv@mail.nih.gov
RI Conroy, Richard/D-1979-2009
OI Conroy, Richard/0000-0002-8896-6090
FU National Institutes of Health
FX National Institutes of Health.
NR 28
TC 3
Z9 3
U1 0
U2 12
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
EI 1527-974X
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD FEB
PY 2014
VL 21
IS E1
BP E2
EP E5
DI 10.1136/amiajnl-2013-001896
PG 4
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Health Care Sciences & Services;
Information Science & Library Science; Medical Informatics
SC Computer Science; Health Care Sciences & Services; Information Science &
Library Science; Medical Informatics
GA AJ4UM
UT WOS:000337672800002
PM 23921193
ER
PT J
AU Alao, H
Liang, TJ
AF Alao, Hawwa
Liang, T. Jake
TI Alternative interferons and immunomodulators in the treatment of
hepatitis C
SO LIVER INTERNATIONAL
LA English
DT Review
DE antiviral drug development; innate immunity; interferon enhancer;
toll-like receptors
ID VIRUS-INFECTION; CLINICAL-TRIAL; ALBINTERFERON ALPHA-2B; CONSENSUS
INTERFERON; RANDOMIZED-TRIAL; INNATE IMMUNITY; DOUBLE-BLIND; GENOTYPE 1;
PHASE 1B; RIBAVIRIN
AB Interferon- (IFN-) has been the mainstay of therapy for hepatitis C and is currently being combined with other drugs to improve the response rate. Newer therapeutic regimens are being developed to spare the use of IFN because of the important side effects associated with IFN-based therapy. However, there may still be a need for the use of IFN in certain populations. In addition, agents that mimic the actions of IFN but with fewer side effects may still be of major value. This review focuses on the development of alternative and new forms of IFNs and other immunomodulatory agents that may supplant IFN- in combination therapy for hepatitis C.
C1 [Alao, Hawwa; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Liang, TJ (reprint author), NIDDK, Liver Dis Branch, NIH, Bldg 10-9B16,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jakel@bdlg10.niddk.nih.gov
FU NIH
FX NIH Funding.
NR 42
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1478-3223
EI 1478-3231
J9 LIVER INT
JI Liver Int.
PD FEB
PY 2014
VL 34
SU 1
SI SI
BP 133
EP 138
DI 10.1111/liv.12402
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AJ2WA
UT WOS:000337524000021
PM 24373090
ER
PT J
AU Leifer, ES
Brawner, CA
Fleg, JL
Kraus, WE
Whellan, DJ
Pina, IL
Keteyian, SJ
AF Leifer, Eric S.
Brawner, Clinton A.
Fleg, Jerome L.
Kraus, William E.
Whellan, David J.
Pina, Ileana L.
Keteyian, Steven J.
TI Are There Negative Responders to Exercise Training among Heart Failure
Patients?
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE AEROBIC CAPACITY; TRAINING PROGRAM; RESPONSE VARIABILITY; NEGATIVE
THRESHOLD
ID TRIAL INVESTIGATING OUTCOMES; HERITAGE FAMILY; HF-ACTION;
REPRODUCIBILITY; UPDATE; HEALTH
AB Purpose: Aerobic exercise training has been used in patients with stable heart failure (HF) to reduce the risk of clinical events. However, due to patient heterogeneity, some patients may experience a decrease in functional capacity due to such training. The purpose of this study was to estimate the proportion of HF patients participating in a training program who had negative responses to such therapy and to compare them with a concurrent control group. Methods: Baseline and 3-month peak (V) over dotO(2) measurements were obtained on 1870 HF subjects who were randomized to receive either an exercise training program or a control program of usual care without exercise training. The exercise program consisted of supervised walking or stationary cycling 3 d.wk(-1) for 12 wk as well as a 2-d.wk(-1) home exercise program after completing 18 supervised sessions. A negative response was defined as a baseline-to-3-month decrease in peak (V) over dotO(2) of at least 5 mL.kg(-1).min(-1), which was two times the SD of the control group's change in peak (V) over dotO(2). Results: The mean T SD change in peak (V) over dotO(2) in the exercise group and control group was 0.8 +/- 2.5 mL.kg(-1).min(-1) and 0.2 +/- 2.5 mL.kg(-1).min(-1), respectively (P < 0.001). The percentage of negative responders in the exercise and control groups was 0.9% and 2.3% (P = 0.02). Conclusions: The low negative response rate in the exercise group combined with the slightly higher rate in the control group and equal variability in the exercise and control groups suggests that few if any subjects had training-related negative peak (V) over dotO(2) responses. These findings support current exercise recommendations for HF patients.
C1 [Leifer, Eric S.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Brawner, Clinton A.; Keteyian, Steven J.] Henry Ford Hosp, Div Cardiovasc Med, Detroit, MI 48202 USA.
[Fleg, Jerome L.] NHLBI, Div Cardiovasc Med, Bethesda, MD 20892 USA.
[Kraus, William E.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Whellan, David J.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA.
[Pina, Ileana L.] Albert Einstein Coll Med, Div Cardiol, Bronx, NY 10467 USA.
RP Keteyian, SJ (reprint author), Henry Ford Hosp, 6525 Second Ave, Detroit, MI 48202 USA.
EM sketeyi1@hfhs.org
OI Brawner, Clinton A./0000-0002-1705-6620
FU National Heart, Lung, and Blood Institute
FX The HF-ACTION trial was supported by grants from the National Heart,
Lung, and Blood Institute. The authors thank the HF-ACTION participants
and investigators who gave their time and effort to completion of the
study. The authors also thank Drs. Nancy Geller, Michael Lauer, and
James Troendle for their critical review of the manuscript. The opinions
and assertions contained herein are the private views of the authors and
are not to be construed as official or as reflecting the views of the
National Heart, Lung, and Blood Institute or the National Institutes of
Health.
NR 14
TC 3
Z9 4
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD FEB
PY 2014
VL 46
IS 2
BP 219
EP 224
DI 10.1249/MSS.0b013e3182a44164
PG 6
WC Sport Sciences
SC Sport Sciences
GA AJ4ZB
UT WOS:000337688000002
PM 23860416
ER
PT J
AU Gibbs, BB
Reis, JP
Schelbert, EB
Craft, LL
Sidney, S
Lima, J
Lewis, CE
AF Gibbs, Bethany Barone
Reis, Jared P.
Schelbert, Erik B.
Craft, Lynette L.
Sidney, Steve
Lima, Joao
Lewis, Cora E.
TI Sedentary Screen Time and Left Ventricular Structure and Function: The
CARDIA Study
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE LEFT VENTRICULAR MASS; SEDENTARY TIME; RACE DIFFERENCES;
ECHOCARDIOGRAPHY
ID RELATIVE WALL THICKNESS; WHITE ADULT MEN; PHYSICAL-ACTIVITY;
CARDIOVASCULAR EVENTS; RISK-FACTORS; LIFE-STYLE; BED REST; MASS;
OBESITY; HYPERTROPHY
AB Introduction: Sedentary screen time (watching TV or using a computer) predicts cardiovascular outcomes independently from moderate and vigorous physical activity and could affect left ventricular structure and function through the adverse consequences of sedentary behavior. Purpose: This study aimed to determine whether sedentary screen time is associated with measures of left ventricular structure and function. Methods: The Coronary Artery Risk Development in Young Adults Study measured screen time by questionnaire and left ventricular structure and function by echocardiography in 2854 black and white participants, age 43-55 yr, in 2010-2011. Generalized linear models evaluated cross-sectional trends for echocardiography measures across higher categories of screen time and adjusting for demographics, smoking, alcohol, and physical activity. Further models adjusted for potential intermediate factors (blood pressure, antihypertensive medication use, diabetes, and body mass index). Results: The relationship between screen time and left ventricular mass (LVM) differed in blacks versus whites. Among whites, higher screen time was associated with larger LVM (P < 0.001), after adjustment for height, demographics, and lifestyle variables. Associations between screen time and LVM persisted when adjusting for blood pressure, antihypertensive medication use, and diabetes (P = 0.008) but not with additional adjustment for body mass index (P = 0.503). Similar relationships were observed for screen time with LVM indexed to height(2.7), relative wall thickness, and mass-to-volume ratio. Screen time was not associated with left ventricular structure among blacks or left ventricular function in either race group. Conclusions: Sedentary screen time is associated with greater LVM in white adults, and this relationship was largely explained by higher overall adiposity. The lack of association in blacks supports a potential qualitative difference in the cardiovascular consequences of sedentary screen-based behavior.
C1 [Gibbs, Bethany Barone; Schelbert, Erik B.] Univ Pittsburgh, Pittsburgh, PA 15203 USA.
[Reis, Jared P.] NHLBI, Bethesda, MD 20892 USA.
[Craft, Lynette L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Sidney, Steve] Kaiser Permanente Div Res, Oakland, CA USA.
[Lima, Joao] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA.
RP Gibbs, BB (reprint author), Univ Pittsburgh, Phys Act & Weight Management Res Ctr, 2100 Wharton St,Suite 600, Pittsburgh, PA 15203 USA.
EM bbarone@pitt.edu
FU Coordinating Center, University of Alabama at Birmingham [N01-HC-95095];
Field Center, University of Alabama [N01-HC-48047]; Field Center and
Diet Reading Center, University of Minnesota [N01-HC-48048];
Northwestern University Field Center [N01-HC-48049]; Kaiser Foundation
Research Institute from the National Heart, Lung, and Blood Institute
[N01-HC-48050]; National Heart, Lung, and Blood Institute
[R01-HL-086792]
FX This study was supported by the Coordinating Center, University of
Alabama at Birmingham (grant no. N01-HC-95095); the Field Center,
University of Alabama (grant no. N01-HC-48047); the Field Center and
Diet Reading Center, University of Minnesota (grant no. N01-HC-48048);
the Northwestern University Field Center (grant no. N01-HC-48049); and
the Kaiser Foundation Research Institute (grant no. N01-HC-48050) from
the National Heart, Lung, and Blood Institute. The CARDIA ECG Ancillary
Study was supported by the National Heart, Lung, and Blood Institute
(grant no. R01-HL-086792).
NR 40
TC 9
Z9 9
U1 3
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD FEB
PY 2014
VL 46
IS 2
BP 276
EP 283
DI 10.1249/MSS.0b013e3182a4df33
PG 8
WC Sport Sciences
SC Sport Sciences
GA AJ4ZB
UT WOS:000337688000009
PM 23863618
ER
PT J
AU Melanson, E
Keadle, SK
Donnelly, JE
Braun, B
King, NA
AF Melanson, Edward
Keadle, Sarah Kozy
Donnelly, Joseph E.
Braun, Barry
King, Neal A.
TI Substitution and Compensation Erode the Energy Deficit from Exercise
Interventions Response
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Letter
ID PHYSICAL-ACTIVITY; MEN; WEIGHT; WOMEN; TIME
C1 [Melanson, Edward] Univ Colorado, Aurora, CO 80045 USA.
[Keadle, Sarah Kozy] NCI, Bethesda, MD 20892 USA.
[Donnelly, Joseph E.] Univ Kansas, Lawrence, KS 66045 USA.
[Braun, Barry] Univ Massachusetts, Amherst, MA 01003 USA.
[King, Neal A.] Queensland Univ Technol, Brisbane, Qld 4001, Australia.
RP Melanson, E (reprint author), Univ Colorado, Anschutz Med Campus, Aurora, CO 80045 USA.
FU NCATS NIH HHS [UL1 TR001082]; NCRR NIH HHS [UL1 RR025780]; NHLBI NIH HHS
[RC1 HL099557]; NIDDK NIH HHS [R01 DK077088]
NR 7
TC 0
Z9 0
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD FEB
PY 2014
VL 46
IS 2
BP 424
EP 424
DI 10.1249/MSS.0000000000000165
PG 1
WC Sport Sciences
SC Sport Sciences
GA AJ4ZB
UT WOS:000337688000027
PM 24435074
ER
PT J
AU Buse, E
Haeger, JD
Svensson-Arvelund, J
Markert, UR
Faas, MM
Ernerudh, J
Dixon, D
Cline, JM
Pfarrer, C
AF Buse, Eberhard
Haeeger, Jan-Dirk
Svensson-Arvelund, Judit
Markert, Udo R.
Faas, Marijke M.
Ernerudh, Jan
Dixon, Darlene
Cline, J. Mark
Pfarrer, Christiane
TI The Placenta in Toxicology. Part I: Animal Models in Toxicology:
Placental Morphology and Tolerance Molecules in the Cynomolgus Monkey
(Macaca fascicularis)
SO TOXICOLOGIC PATHOLOGY
LA English
DT Review
DE cynomolgus monkey; animal models; placental morphology; HLA; FAS-ligand;
IDO; annexin II
ID INDOLEAMINE 2,3-DIOXYGENASE; HLA-G; TRYPTOPHAN CATABOLISM; ANNEXIN II;
EXTRAVILLOUS TROPHOBLAST; IMMUNE PRIVILEGE; CORROSION CAST;
UP-REGULATION; FAS LIGAND; T-CELLS
AB The immune system represents a key defense mechanism against potential pathogens and adverse non-self materials. During pregnancy, the placenta is the point of contact between the maternal organism and non-self proteins of the fetal allograft and hence undoubtedly fulfils immune functions. In the placenta bacteria, foreign (non-self) proteins and proteins that might be introduced in toxicological studies or by medication are barred from reaching the progeny, and the maternal immune system is primed for acceptance of non-maternal fetal protein. Both immunologic protection of the fetus and acceptance of the fetus by the mother require effective mechanisms to prevent an immunologic fetomaternal conflict and to keep both organisms in balance. This is why the placenta requires toxicological consideration in view of its immune organ function. The following articles deal with placenta immune-, control-, and tolerance mechanisms in view of both fetal and maternal aspects. Furthermore, models for experimental access to placental immune function are addressed and the pathological evaluation is elucidated. "The Placenta as an Immune Organ and Its Relevance in Toxicological Studies'' was subject of a continuing education course at the 2012 Society of Toxicologic Pathology meeting held in Boston, MA.
C1 [Buse, Eberhard] Covance Labs GmbH, D-48163 Munster, Germany.
[Haeeger, Jan-Dirk; Pfarrer, Christiane] Univ Vet Med, Dept Anat, Hannover, Germany.
[Svensson-Arvelund, Judit; Ernerudh, Jan] Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, S-58183 Linkoping, Sweden.
[Markert, Udo R.] Univ Hosp, Dept Obstet, Placenta Lab, Jena, Germany.
[Faas, Marijke M.] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Div Med Biol, NL-9700 AB Groningen, Netherlands.
[Dixon, Darlene] NIEHS, NTP, Res Triangle Pk, NC 27709 USA.
[Cline, J. Mark] Wake Forest Sch Med, Dept Pathol, Comparat Med Sect, Winston Salem, NC USA.
RP Buse, E (reprint author), Covance Labs GmbH, Kesselfeld 29, D-48163 Munster, Germany.
EM e.h.buse@googlemail.com
RI Haeger, Jan-Dirk/B-6893-2016;
OI Svensson-Arvelund, Judit/0000-0002-6260-0808
NR 82
TC 2
Z9 2
U1 1
U2 9
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD FEB
PY 2014
VL 42
IS 2
BP 314
EP 326
DI 10.1177/0192623313482208
PG 13
WC Pathology; Toxicology
SC Pathology; Toxicology
GA AJ4ES
UT WOS:000337625300003
PM 23548606
ER
PT J
AU Svensson-Arvelund, J
Ernerudh, J
Buse, E
Cline, JM
Haeger, JD
Dixon, D
Markert, UR
Pfarrer, C
De Vos, P
Faas, MM
AF Svensson-Arvelund, Judit
Ernerudh, Jan
Buse, Eberhard
Cline, J. Mark
Haeger, Jan-Dirk
Dixon, Darlene
Markert, Udo R.
Pfarrer, Christiane
De Vos, Paul
Faas, Marijke M.
TI The Placenta in Toxicology. Part II: Systemic and Local Immune
Adaptations in Pregnancy
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE pregnancy; immune regulation; tolerance; leukocytes; decidua; placenta
ID NATURAL-KILLER-CELLS; REGULATORY T-CELLS; MATERNAL-FETAL INTERFACE;
DECIDUAL NK CELLS; ADENOSINE DIPHOSPHATASE ACTIVITY; HUMAN
CHORIONIC-GONADOTROPIN; LYMPHOID DENDRITIC CELLS; BLOOD
MONONUCLEAR-CELLS; NECROSIS-FACTOR-ALPHA; LOW-DOSE ENDOTOXIN
AB During pregnancy, the maternal immune system is challenged by the semiallogeneic fetus, which must be tolerated without compromising fetal or maternal health. This review updates the systemic and local immune changes taking place during human pregnancy, including some examples in rodents. Systemic changes are induced by contact of maternal blood with placental factors and include enhanced innate immunity with increased activation of granulocytes and nonclassical monocytes. Although a bias toward T helper (Th2) and regulatory T cell (Treg) immunity has been associated with healthy pregnancy, the relationship between different circulating Th cell subsets is not straightforward. Instead, these adaptations appear most evidently at the fetal-maternal interface, where for instance Tregs are enriched and promote fetal tolerance. Also innate immune cells, that is, natural killer cells and macrophages, are enriched, constituting the majority of decidual leukocytes. These cells not only contribute to immune regulation but also aid in establishing the placenta by promoting trophoblast recruitment and angiogenesis. Thus, proper interaction between leukocytes and placental trophoblasts is necessary for normal placentation and immune adaptation. Consequently, spontaneous maladaptation or interference of the immune system with toxic substances may be important contributing factors for the development of pregnancy complications such as preeclampsia, preterm labor, and recurrent miscarriages.
C1 [Svensson-Arvelund, Judit; Ernerudh, Jan] Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, S-58185 Linkoping, Sweden.
[Buse, Eberhard] Covance Labs, Munster, Germany.
[Cline, J. Mark] Wake Forest Sch Med, Comparat Med Sect, Dept Pathol, Winston Salem, NC USA.
[Haeger, Jan-Dirk; Pfarrer, Christiane] Univ Vet Med, Dept Anat, Hannover, Germany.
[Dixon, Darlene] NIEHS, NTP, NTP Lab, Res Triangle Pk, NC 27709 USA.
[Markert, Udo R.] Univ Hosp, Dept Obstet, Placenta Lab, Jena, Germany.
[De Vos, Paul; Faas, Marijke M.] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Div Med Biol, NL-9713 AV Groningen, Netherlands.
[De Vos, Paul; Faas, Marijke M.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
RP Svensson-Arvelund, J (reprint author), Linkoping Univ, AIR, Dept Clin & Expt Med, Fac Hlth Sci, Patologihuset Plan 10, S-58185 Linkoping, Sweden.
EM judit.svensson@liu.se
RI Haeger, Jan-Dirk/B-6893-2016;
OI Svensson-Arvelund, Judit/0000-0002-6260-0808
NR 162
TC 17
Z9 17
U1 2
U2 21
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD FEB
PY 2014
VL 42
IS 2
BP 327
EP 338
DI 10.1177/0192623313482205
PG 12
WC Pathology; Toxicology
SC Pathology; Toxicology
GA AJ4ES
UT WOS:000337625300004
PM 23531796
ER
PT J
AU Cline, JM
Dixon, D
Ernerudh, J
Faas, MM
Gohner, C
Hager, JD
Markert, UR
Pfarrer, C
Svensson-Arvelund, J
Buse, E
AF Cline, J. Mark
Dixon, Darlene
Ernerudh, Jan
Faas, Marijke M.
Goehner, Claudia
Haeger, Jan-Dirk
Markert, Udo R.
Pfarrer, Christiane
Svensson-Arvelund, Judit
Buse, Eberhard
TI The Placenta in Toxicology. Part III: Pathologic Assessment of the
Placenta
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE macaca; mus; rodent pathology; primate pathology; placenta; toxicology
ID RAT PLACENTA; FETAL; PREGNANCY; MICE; EXPRESSION; MORPHOLOGY; GESTATION;
MACAQUE; LESIONS; WEIGHT
AB This short review is derived from the peer-reviewed literature and the experience and case materials of the authors. Brief illustrated summaries are presented on the gross and histologic normal anatomy of rodent and macaque placentas, including typical organ weights, with comments on differences from the human placenta. Common incidental findings, background lesions, and induced toxic lesions are addressed, and a recommended strategy for pathologic evaluation of placentas is provided.
C1 [Cline, J. Mark] Wake Forest Sch Med, Comparat Med Sect, Dept Pathol, Winston Salem, NC 27157 USA.
[Dixon, Darlene] NIEHS, NTP, NTP Lab, Res Triangle Pk, NC 27709 USA.
[Ernerudh, Jan; Svensson-Arvelund, Judit] Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, Linkoping, Sweden.
[Faas, Marijke M.] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Div Med Biol, Groningen, Netherlands.
[Goehner, Claudia; Markert, Udo R.] Univ Hosp Jena, Dept Obstet, Placenta Lab, Jena, Germany.
[Haeger, Jan-Dirk; Pfarrer, Christiane] Univ Vet Med Hannover, Dept Anat, Hannover, Germany.
[Buse, Eberhard] Covance Labs GmbH, Munster, Germany.
RP Cline, JM (reprint author), Wake Forest Sch Med, Comparat Med Sect, Dept Pathol, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM jmcline@wakehealth.edu
RI Haeger, Jan-Dirk/B-6893-2016;
OI Svensson-Arvelund, Judit/0000-0002-6260-0808; Gohner,
Claudia/0000-0001-9309-914X
NR 28
TC 0
Z9 0
U1 1
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD FEB
PY 2014
VL 42
IS 2
BP 339
EP 344
DI 10.1177/0192623313482207
PG 6
WC Pathology; Toxicology
SC Pathology; Toxicology
GA AJ4ES
UT WOS:000337625300005
PM 23531795
ER
PT J
AU Gohner, C
Svensson-Arvelund, J
Pfarrer, C
Hager, JD
Faas, M
Ernerudh, J
Cline, JM
Dixon, D
Buse, E
Markert, UR
AF Goehner, Claudia
Svensson-Arvelund, Judit
Pfarrer, Christiane
Haeger, Jan-Dirk
Faas, Marijke
Ernerudh, Jan
Cline, J. Mark
Dixon, Darlene
Buse, Eberhard
Markert, Udo R.
TI The Placenta in Toxicology. Part IV: Battery of Toxicological Test
Systems Based on Human Placenta
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE trophoblast; placenta; placenta perfusion; placenta explant;
choriocarcinoma; human toxicology
ID HUMAN CHORIOCARCINOMA CELLS; HUMAN TROPHOBLAST; BISPHENOL-A; IN-VIVO;
EXPRESSION; PERFUSION; JEG-3; ACCUMULATION; METABOLISM; TRANSPORT
AB This review summarizes the potential and also some limitations of using human placentas, or placental cells and structures for toxicology testing. The placenta contains a wide spectrum of cell types and tissues, such as trophoblast cells, immune cells, fibroblasts, stem cells, endothelial cells, vessels, glands, membranes, and many others. It may be expected that in many cases the relevance of results obtained from human placenta will be higher than those from animal models due to species specificity of metabolism and placental structure. For practical and economical reasons, we propose to apply a battery of sequential experiments for analysis of potential toxicants. This should start with using cell lines, followed by testing placenta tissue explants and isolated placenta cells, and finally by application of single and dual side ex vivo placenta perfusion. With each of these steps, the relative workload increases while the number of feasible repeats decreases. Simultaneously, the predictive power enhances by increasing similarity with in vivo human conditions. Toxic effects may be detected by performing proliferation, vitality and cell death assays, analysis of protein and hormone expression, immunohistochemistry or testing functionality of signaling pathways, gene expression, transport mechanisms, and so on. When toxic effects appear at any step, the subsequent assays may be cancelled. Such a system may be useful to reduce costs and increase specificity in testing questionable toxicants. Nonetheless, it requires further standardization and end point definitions for better comparability of results from different toxicants and to estimate the respective in vivo translatability and predictive value.
C1 [Goehner, Claudia; Markert, Udo R.] Univ Hosp, Dept Obstet, Placenta Lab, Jena, Germany.
[Svensson-Arvelund, Judit; Ernerudh, Jan] Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, S-58183 Linkoping, Sweden.
[Pfarrer, Christiane; Haeger, Jan-Dirk] Univ Vet Med Hannover, Dept Anat, Hannover, Germany.
[Faas, Marijke] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Div Med Biol, Groningen, Netherlands.
[Cline, J. Mark] Wake Forest Sch Med, Comparat Med Sect, Dept Pathol, Winston Salem, NC USA.
[Dixon, Darlene] NIEHS, NTP, NTP Lab, Res Triangle Pk, NC 27709 USA.
[Buse, Eberhard] Covance Labs, Munster, Germany.
RP Markert, UR (reprint author), Univ Jena, Ernst Abbe Pl 8, D-07743 Jena, Germany.
EM udo.markert@med.uni-jena.de
RI Haeger, Jan-Dirk/B-6893-2016;
OI Svensson-Arvelund, Judit/0000-0002-6260-0808; Gohner,
Claudia/0000-0001-9309-914X
FU German Ministry of Research (BMBF)
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: CG is
supported by a research grant from the German Ministry of Research
(BMBF).
NR 59
TC 2
Z9 2
U1 0
U2 8
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD FEB
PY 2014
VL 42
IS 2
BP 345
EP 351
DI 10.1177/0192623313482206
PG 7
WC Pathology; Toxicology
SC Pathology; Toxicology
GA AJ4ES
UT WOS:000337625300006
PM 23548605
ER
PT J
AU Cesta, MF
Malarkey, DE
Herbert, RA
Brix, A
Hamlin, MH
Singletary, E
Sills, RC
Bucher, JR
Birnbaum, LS
AF Cesta, Mark F.
Malarkey, David E.
Herbert, Ronald A.
Brix, Amy
Hamlin, Melvin H., II
Singletary, Emily
Sills, Robert C.
Bucher, John R.
Birnbaum, Linda S.
TI The National Toxicology Program Web-based Nonneoplastic Lesion Atlas: A
Global Toxicology and Pathology Resource
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE National Toxicology Program; NTP; atlas; nonneoplastic lesion;
toxicologic pathology
ID EXPOSURE
AB Toxicologists and pathologists worldwide will benefit from a new, website-based, and completely searchable Nonneoplastic Lesion Atlas just released by the U. S. National Toxicology Program (NTP). The atlas is a much-needed resource with thousands of high-quality, zoomable images and diagnostic guidelines for each rodent lesion. Liver, gallbladder, nervous system, bone marrow, lower urinary tract and skin lesion images, and diagnostic strategies are available now. More organ and biological systems will be added with a total of 22 chapters planned for the completed project. The atlas will be used by the NTP and its many pathology partners to standardize lesion diagnosis, terminology, and the way lesions are recorded. The goal is to improve our understanding of nonneoplastic lesions and the consistency and accuracy of their diagnosis between pathologists and laboratories. The atlas is also a useful training tool for pathology residents and can be used to bolster any organization's own lesion databases. Researchers have free access to this online resource at http://ntp.niehs.nih.gov/nnl.
C1 [Cesta, Mark F.; Malarkey, David E.; Herbert, Ronald A.; Sills, Robert C.; Bucher, John R.; Birnbaum, Linda S.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Brix, Amy; Hamlin, Melvin H., II; Singletary, Emily] Expt Pathol Labs Inc, Durham, NC 27713 USA.
RP Cesta, MF (reprint author), NIEHS, Cellular & Mol Pathol Branch, POB 12233,MD B3-06, Res Triangle Pk, NC 27709 USA.
EM cesta@niehs.nih.gov
FU Division of the National Toxicology Program. of the NIH, National
Institute of Environmental Health Sciences (NIEHS)
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
research was supported by the Division of the National Toxicology
Program. of the NIH, National Institute of Environmental Health Sciences
(NIEHS).
NR 9
TC 4
Z9 4
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD FEB
PY 2014
VL 42
IS 2
BP 458
EP 460
DI 10.1177/0192623313517304
PG 3
WC Pathology; Toxicology
SC Pathology; Toxicology
GA AJ4ES
UT WOS:000337625300015
PM 24488020
ER
PT J
AU Ruiz, A
Heilmann, S
Becker, T
Hernandez, I
Wagner, H
Thelen, M
Mauleon, A
Rosende-Roca, M
Bellenguez, C
Bis, JC
Harold, D
Gerrish, A
Sims, R
Sotolongo-Grau, O
Espinosa, A
Alegret, M
Arrieta, JL
Lacour, A
Leber, M
Becker, J
Lafuente, A
Ruiz, S
Vargas, L
Rodriguez, O
Ortega, G
Dominguez, MA
Mayeux, R
Haines, JL
Pericak-Vance, MA
Farrer, LA
Schellenberg, GD
Chouraki, V
Launer, LJ
van Duijn, C
Seshadri, S
Antunez, C
Breteler, MM
Serrano-Rios, M
Jessen, F
Tarraga, L
Nothen, MM
Maier, W
Boada, M
Ramirez, A
AF Ruiz, A.
Heilmann, S.
Becker, T.
Hernandez, I.
Wagner, H.
Thelen, M.
Mauleon, A.
Rosende-Roca, M.
Bellenguez, C.
Bis, J. C.
Harold, D.
Gerrish, A.
Sims, R.
Sotolongo-Grau, O.
Espinosa, A.
Alegret, M.
Arrieta, J. L.
Lacour, A.
Leber, M.
Becker, J.
Lafuente, A.
Ruiz, S.
Vargas, L.
Rodriguez, O.
Ortega, G.
Dominguez, M-A
Mayeux, R.
Haines, J. L.
Pericak-Vance, M. A.
Farrer, L. A.
Schellenberg, G. D.
Chouraki, V.
Launer, L. J.
van Duijn, C.
Seshadri, S.
Antunez, C.
Breteler, M. M.
Serrano-Rios, M.
Jessen, F.
Tarraga, L.
Noethen, M. M.
Maier, W.
Boada, M.
Ramirez, A.
CA IGAP
TI Follow-up of loci from the International Genomics of Alzheimer's Disease
Project identifies TRIP4 as a novel susceptibility gene
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
DE dementia risk; DNA; GWAS; molecular epidemiology; SNP; thyroid receptor
ID WIDE ASSOCIATION; COMMON VARIANTS; POPULATION; CD2AP; EPHA1; CD33; APOE;
CLU; AD
AB To follow-up loci discovered by the International Genomics of Alzheimer's Disease Project, we attempted independent replication of 19 single nucleotide polymorphisms (SNPs) in a large Spanish sample (Fundacio ACE data set; 1808 patients and 2564 controls). Our results corroborate association with four SNPs located in the genes INPP5D, MEF2C, ZCWPW1 and FERMT2, respectively. Of these, ZCWPW1 was the only SNP to withstand correction for multiple testing (P = 0.000655). Furthermore, we identify TRIP4 (rs74615166) as a novel genome-wide significant locus for Alzheimer's disease risk (odds ratio = 1.31; confidence interval 95% (1.19-1.44); P = 9.74 x 10(-9)).
C1 [Ruiz, A.; Hernandez, I.; Mauleon, A.; Rosende-Roca, M.; Sotolongo-Grau, O.; Espinosa, A.; Alegret, M.; Lafuente, A.; Ruiz, S.; Vargas, L.; Rodriguez, O.; Ortega, G.; Dominguez, M-A; Tarraga, L.; Boada, M.] Inst Catala Neurociencies Aplicades, Memory Clin, Fundacio ACE, Barcelona, Spain.
[Heilmann, S.; Noethen, M. M.; Ramirez, A.] Univ Bonn, Inst Human Genet, D-53105 Bonn, Germany.
[Heilmann, S.; Noethen, M. M.] Univ Bonn, Dept Genom, Life & Brain Ctr, D-53105 Bonn, Germany.
[Becker, T.; Lacour, A.; Leber, M.; Breteler, M. M.; Jessen, F.; Maier, W.] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany.
[Becker, T.] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-53105 Bonn, Germany.
[Wagner, H.; Thelen, M.; Becker, J.; Jessen, F.; Maier, W.; Ramirez, A.] Univ Bonn, Dept Psychiat & Psychotherapy, D-53105 Bonn, Germany.
[Bellenguez, C.] INSERM, U744, F-59045 Lille, France.
[Bellenguez, C.] Univ Lille 2, Lille, France.
[Bellenguez, C.] Inst Pasteur, F-59019 Lille, France.
[Bis, J. C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Harold, D.; Gerrish, A.; Sims, R.] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales.
[Arrieta, J. L.] Univ Hosp La Paz Cantoblanco, Memory Unit, Madrid, Spain.
[Mayeux, R.] Columbia Univ, Dept Neurol, Taub Inst Alzheimers Dis & Aging Brain, New York, NY USA.
[Mayeux, R.] Columbia Univ, Gertrude H Sergievsky Ctr, Dept Neurol, New York, NY 10027 USA.
[Haines, J. L.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
[Haines, J. L.] Vanderbilt Univ, Vanderbilt Ctr Human Genet Res, Nashville, TN 37235 USA.
[Pericak-Vance, M. A.] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA.
[Pericak-Vance, M. A.] Univ Miami, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL USA.
[Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Med Biomed Genet, Boston, MA USA.
[Farrer, L. A.] Boston Univ, Dept Ophthalmol, Sch Publ Hlth, Boston, MA USA.
[Farrer, L. A.] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA USA.
[Farrer, L. A.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA.
[Farrer, L. A.; Chouraki, V.; Seshadri, S.; Noethen, M. M.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Schellenberg, G. D.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Launer, L. J.] NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[van Duijn, C.] Erasmus MC Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[van Duijn, C.] Erasmus MC Univ Med Ctr, Dept Neurol, Rotterdam, Netherlands.
[van Duijn, C.] Erasmus MC Univ Med Ctr, Dept Radiol, Rotterdam, Netherlands.
[van Duijn, C.] Netherlands Consortium Hlth Aging, Leiden, Netherlands.
[van Duijn, C.] Ctr Med Syst Biol, Leiden, Netherlands.
[Antunez, C.] Univ Hosp Virgen de la Arrixaca, Dementia Unit, Murcia, Spain.
[Serrano-Rios, M.] Hosp Clin San Carlos, CIBERDEM Spain, Madrid, Spain.
[Boada, M.] Univ Autonoma Barcelona VHIR UAB, Hosp Univ Vall dHebron, Inst Recerca, Barcelona, Spain.
RP Ramirez, A (reprint author), Univ Bonn, Dept Psychiat & Psychotherapy, Sigmund Freud Str 25, D-53105 Bonn, Germany.
EM alfredo.ramirez@ukb.uni-bonn.de
RI Breteler, Monique /J-5058-2014;
OI Sotolongo-Grau, Oscar/0000-0002-9679-0670; Farrer,
Lindsay/0000-0001-5533-4225; Seshadri, Sudha/0000-0001-6135-2622;
Chouraki, Vincent/0000-0002-4698-1794; Harold,
Denise/0000-0001-5195-0143; Lacour, Andre/0000-0003-2692-2583; Nothen,
Markus/0000-0002-8770-2464
FU Fundacio ACE research programs; CIBER de Diabetes y Enfermedades
Metabolicas Asociadas (CIBERDEM); CIBERNED are Instituto de Salud Carlos
III ISCIII Projects
FX We thank all patients and controls for their participation in this
project. We thank all of the investigators from the International
Genomics of Alzheimer Project (IGAP) consortium for their close
collaboration and intellectual input, and for sharing their
pre-publication data in order to permit rapid completion of this
research work. The IGAP comprises four major Alzheimer's disease
research groups: the Alzheimer Disease Genetics Consortium (ADGC); the
Neurology Working Group of the Cohorts for Heart and Aging Research in
Genomic Epidemiology (CHARGE); the European Initiative for Alzheimer
Disease (EADI); and the Genetic and Environmental Risk in Alzheimer's
Disease (GERAD). We are indebted to Trinitat Port-Carbo and her family
for their support of the Fundacio ACE research programs. Fundacio ACE
collaborates with the Centro de Investigacion Biomedica en Red sobre
Enfermedades Neurodegenerativas (CIBERNED, Spain), and is one of the
participating centers of the Dementia Genetics Spanish Consortium
(DEGESCO). The Diabetes Research Laboratory, Biomedical Research
Foundation at University Hospital Clnico San Carlos received support
from CIBER de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM).
CIBERDEM and CIBERNED are Instituto de Salud Carlos III ISCIII Projects.
Agustin Ruiz is supported by grant PI13/02434 (Accion Estrategica en
Salud. Instituto de Salud Carlos III (ISCIII). Ministerio de Economia y
Competitividad, Spain). Tim Becker and Markus M Nothen are members of
the DFG-funded Excellence Cluster ImmunoSensation. This study was funded
in part by the National institute of Health (NIH) project AG033193 to
CHARGE. This publication was funded in part by the German Federal
Ministry of Education and Research (grants KND: 01GI0102, 01GI0420,
01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433, 01GI0434; grants KNDD:
01GI0710, 01GI0711, 01GI0712, 01GI0713, 01GI0714, 01GI0715, 01GI0716,
01ET1006B).
NR 19
TC 23
Z9 23
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD FEB
PY 2014
VL 4
AR e358
DI 10.1038/tp.2014.2
PG 4
WC Psychiatry
SC Psychiatry
GA AJ2RP
UT WOS:000337508200003
PM 24495969
ER
PT J
AU McDermott, MM
Liu, KA
Ferrucci, L
Tian, L
Guralnik, J
Kopp, P
Van Horn, L
Liao, YH
Green, D
Kibbe, M
Sufit, R
Zhao, LH
Criqui, MH
AF McDermott, Mary M.
Liu, Kiang
Ferrucci, Luigi
Tian, Lu
Guralnik, Jack
Kopp, Peter
Van Horn, Linda
Liao, Yihua
Green, David
Kibbe, Melina
Sufit, Robert
Zhao, Lihui
Criqui, Michael H.
TI Vitamin D status, functional decline, and mortality in peripheral artery
disease
SO VASCULAR MEDICINE
LA English
DT Article
DE exercise; intermittent claudication; peripheral arterial disease;
peripheral vascular diseases; walking
ID ANKLE BRACHIAL INDEX; SERUM 25-HYDROXYVITAMIN D; LOWER-EXTREMITY
ISCHEMIA; 1,25-DIHYDROXYVITAMIN-D3 RECEPTORS; PHYSICAL-ACTIVITY;
BLOOD-PRESSURE; OLDER-ADULTS; MUSCLE; RISK; ASSOCIATION
AB Associations of vitamin D levels with prospectively measured functional decline and mortality in people with lower extremity peripheral artery disease (PAD) are unknown. We determined whether lower baseline vitamin D levels are associated with a faster decline in functional performance and higher mortality among people with and without PAD. A total of 658 participants (395 with PAD) underwent baseline measurement of 25-hydroxyvitamin D (DiaSorin radioimmunoassay), a 6-minute walk test, 4-meter walking velocity and the Short Physical Performance Battery (SPPB), and were followed annually for up to 4 years. Analyses were adjusted for age, sex, race, body mass index, comorbidities, the ankle-brachial index, and other confounders. Among participants with PAD, lower baseline vitamin D levels were associated with a faster decline in the 6-minute walk (vitamin D < 30 nmol/L: -70.0 feet/year; vitamin D 30 to < 50 nmol/L: -72.3 feet/year; vitamin D 50 to < 75 nmol/L: -35.5 feet/year; vitamin D 75 to < 120 nmol/L: -35.9 feet/year; p trend=0.012). PAD participants with vitamin D < 30 nmol/L had a faster decline in the SPPB and 6-minute walk compared to those with levels of 50 to < 75 (p=0.034 and p=0.04, respectively). Among participants without PAD, lower vitamin D was associated with a faster decline in the fast 4-meter walking velocity (p trend=0.003). There were no significant associations of baseline vitamin D levels with all-cause or cardiovascular disease mortality in PAD or non-PAD participants. In conclusion, among individuals with and without PAD, low vitamin D status was associated with a faster decline in some measures of functional performance but was not related to mortality.
C1 [McDermott, Mary M.; Liu, Kiang; Kopp, Peter; Van Horn, Linda; Liao, Yihua; Green, David; Kibbe, Melina; Sufit, Robert; Zhao, Lihui] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
[Tian, Lu] Stanford Univ, Palo Alto, CA 94304 USA.
[Guralnik, Jack] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Criqui, Michael H.] Univ Calif San Diego, San Diego, CA 92103 USA.
RP McDermott, MM (reprint author), Northwestern Univ, Feinberg Sch Med, 750 Lake Shore Dr,10th Floor, Chicago, IL 60611 USA.
EM mdm608@northwestern.edu
FU National Heart, Lung, and Blood Institute; Office of Dietary
Supplements, National Institutes of Health (Bethesda, MD, USA)
[R01-HL096849]; National Institute on Aging (Bethesda, MD, USA)
FX Funded by the National Heart, Lung, and Blood Institute and by the
Office of Dietary Supplements, National Institutes of Health
(R01-HL096849) (Bethesda, MD, USA). Supported by the National Institute
on Aging (Bethesda, MD, USA).
NR 30
TC 5
Z9 5
U1 0
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1358-863X
EI 1477-0377
J9 VASC MED
JI Vasc. Med.
PD FEB
PY 2014
VL 19
IS 1
BP 18
EP 26
DI 10.1177/1358863X13518364
PG 9
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AJ3PO
UT WOS:000337579400003
PM 24442622
ER
PT J
AU Smith, JA
Colbert, RA
AF Smith, Judith A.
Colbert, Robert A.
TI The Interleukin-23/Interleukin-17 Axis in Spondyloarthritis Pathogenesis
Th17 and Beyond
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Review
ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; HLA-B27
TRANSGENIC RATS; PLACEBO-CONTROLLED TRIAL; T-HELPER-CELLS;
INTERLEUKIN-12/23 MONOCLONAL-ANTIBODY; SOCIETY CLASSIFICATION CRITERIA;
PRONE HLA-B27-TRANSGENIC RATS; INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE
ASSOCIATION
C1 [Smith, Judith A.] Univ Wisconsin, Madison, WI 53706 USA.
[Colbert, Robert A.] NIAMSD, Bethesda, MD 20892 USA.
RP Colbert, RA (reprint author), NIAMSD, Pediat Translat Res Branch, NIH, CRC, Bldg 10,Room 1-5142,10 Ctr Dr,MSC 1102, Bethesda, MD 20892 USA.
EM colbertr@mail.nih.gov
FU Rheumatology Research Foundation; NIH (National Institute of Arthritis
and Musculoskeletal and Skin Diseases) [Z01-AR-041184]
FX Dr. Smith's work was supported by the Rheumatology Research Foundation
(Disease Targeted Research pilot grant and Disease Targeted Innovative
Research grant). Dr. Colbert's work was supported by the NIH (National
Institute of Arthritis and Musculoskeletal and Skin Diseases Intramural
Research Program grant Z01-AR-041184).
NR 132
TC 30
Z9 34
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD FEB
PY 2014
VL 66
IS 2
BP 231
EP 241
DI 10.1002/art.38291
PG 11
WC Rheumatology
SC Rheumatology
GA AJ0PQ
UT WOS:000337357900001
PM 24504793
ER
PT J
AU Terrier, B
Nagata, S
Ise, T
Rosenzwajg, M
Pastan, I
Klatzmann, D
Saadoun, D
Cacoub, P
AF Terrier, Benjamin
Nagata, Satoshi
Ise, Tomoko
Rosenzwajg, Michelle
Pastan, Ira
Klatzmann, David
Saadoun, David
Cacoub, Patrice
TI CD21(-/low) Marginal Zone B Cells Highly Express Fc Receptor-like 5
Protein and Are Killed by Anti-Fc Receptor-like 5 Immunotoxins in
Hepatitis C Virus-Associated Mixed Cryoglobulinemia Vasculitis
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; HCV-INFECTED PATIENTS; II
CRYOGLOBULINEMIA; RECOMBINANT IMMUNOTOXIN; VILLOUS LYMPHOCYTES;
MULTIPLE-MYELOMA; SPLENIC LYMPHOMA; MALIGNANT-CELLS; MOLECULES;
EXPANSION
AB Objective. Hepatitis C virus (HCV) is associated with B cell lymphoproliferative disorders, including mixed cryoglobulinemia (MC) vasculitis and B cell non-Hodgkin's lymphoma. The expansion of clonal and autoreactive rheumatoid factor-bearing CD21(-/low) marginal zone (MZ) B cells was demonstrated in patients with HCV-associated MC vasculitis. Fc receptor-like (FCRL) proteins comprise a family of immunoregulatory proteins preferentially expressed on B lineage cells. The goal of this study was to investigate the expression of FCRL proteins 1-5 on B cells from patients with HCV-associated MC vasculitis.
Methods. Expression of FCRL proteins 1-5 was assessed by flow cytometry on B cells from 15 HCV-infected patients with type II MC (7 of whom had B cell non-Hodgkin's lymphoma), 20 HCV-infected patients without MC, and 20 healthy donors. To evaluate FCRL-5 as an immunotherapy target in HCV-associated MC vasculitis, 2 anti-FCRL-5 recombinant immunotoxins were produced using anti-FCRL-5 monoclonal antibodies and Pseudomonas exotoxin.
Results. Expression of FCRLs 2, 3, and 5 was markedly increased while expression of FCRL-1 was decreased on clonal CD21(-/low) MZ B cells, as compared with other B cell subsets, from HCV-infected patients and healthy donors. However, there was no difference in the pattern of FCRL expression between HCV-MC patients with lymphoma and those without lymphoma. The anti-FCRL-5 immunotoxins showed specific cytotoxicity against FCRL-5-expressing clonal CD21(-/low) MZ B cells isolated from HCV-infected patients as well as FCRL-5-transfected cell lines. No cytotoxicity against T cells or conventional B cells was observed.
Conclusion. These findings suggest that FCRL-5-targeting therapies could be a specific treatment for HCV-associated MC vasculitis and other FCRL-5-positive autoimmune B cell disorders.
C1 [Terrier, Benjamin; Saadoun, David; Cacoub, Patrice] Grp Hosp Pitie Salpetriere, CNRS, UMR 7211, INSERM,U959, F-75634 Paris, France.
[Terrier, Benjamin; Saadoun, David; Cacoub, Patrice] Univ Paris 06, Paris, France.
[Nagata, Satoshi; Ise, Tomoko] Univ S Dakota, Canc Biol Res Ctr, Sanford Res, Sioux Falls, SD USA.
[Rosenzwajg, Michelle; Klatzmann, David] INSERM, U959, CNRS, UMR 7211, Paris, France.
[Rosenzwajg, Michelle; Klatzmann, David] Grp Hosp Pitie Salpetriere, F-75634 Paris, France.
[Pastan, Ira] NCI, NIH, Bethesda, MD 20892 USA.
RP Terrier, B (reprint author), Hop La Pitie Salpetriere, CNRS UPMC, UMR 7211, Dept Internal Med,INSERM,U959, 47-83 Blvd Hop, F-75013 Paris, France.
EM benj.terrier@gmail.com
FU Fondation pour la Recherche Medicale; Agence Nationale pour la Recherche
sur le Sida et les Hepatites; Societe Nationale Francaise de Medecine
Interne; Leukemia Research Foundation; CLL Global Research Foundation;
NIH [1P20-RR-024219-01A2]; NIH Intramural Research Program, National
Cancer Institute, Center for Cancer Research
FX Dr. Terrier's work was supported by the Fondation pour la Recherche
Medicale, the Agence Nationale pour la Recherche sur le Sida et les
Hepatites, and the Societe Nationale Francaise de Medecine Interne. Dr.
Nagata's work was supported by the Leukemia Research Foundation, the CLL
Global Research Foundation, and the NIH (grant 1P20-RR-024219-01A2). Dr.
Pastan's work was supported by the NIH Intramural Research Program,
National Cancer Institute, Center for Cancer Research.
NR 43
TC 3
Z9 3
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD FEB
PY 2014
VL 66
IS 2
BP 433
EP 443
DI 10.1002/art.38222
PG 11
WC Rheumatology
SC Rheumatology
GA AJ0PQ
UT WOS:000337357900026
PM 24504816
ER
PT J
AU McGuire, PJ
Tarasenko, TN
Wang, T
Levy, E
Zerfas, PM
Moran, T
Lee, HS
Bequette, BJ
Diaz, GA
AF McGuire, Peter J.
Tarasenko, Tatiana N.
Wang, Tony
Levy, Ezra
Zerfas, Patricia M.
Moran, Thomas
Lee, Hye Seung
Bequette, Brian J.
Diaz, George A.
TI Acute metabolic decompensation due to influenza in a mouse model of
ornithine transcarbamylase deficiency
SO DISEASE MODELS & MECHANISMS
LA English
DT Article
DE Urea cycle disorder; Hyperammonemia; Infection; Influenza
ID UREA CYCLE DISORDERS; SPF-ASH MICE; PHOSPHATE SYNTHETASE; AMMONIA
METABOLISM; OTC(SPF-ASH) MICE; ADAPTIVE IMMUNITY; OTC DEFICIENCY; LIVER;
VIRUS; ADULT
AB The urea cycle functions to incorporate ammonia, generated by normal metabolism, into urea. Urea cycle disorders (UCDs) are caused by loss of function in any of the enzymes responsible for ureagenesis, and are characterized by life-threatening episodes of acute metabolic decompensation with hyperammonemia (HA). A prospective analysis of interim HA events in a cohort of individuals with ornithine transcarbamylase (OTC) deficiency, the most common UCD, revealed that intercurrent infection was the most common precipitant of acute HA and was associated with markers of increased morbidity when compared with other precipitants. To further understand these clinical observations, we developed a model system of metabolic decompensation with HA triggered by viral infection (PR8 influenza) using spf-ash mice, a model of OTC deficiency. Both wild-type (WT) and spf-ash mice displayed similar cytokine profiles and lung viral titers in response to PR8 influenza infection. During infection, spf-ash mice displayed an increase in liver transaminases, suggesting a hepatic sensitivity to the inflammatory response and an altered hepatic immune response. Despite having no visible pathological changes by histology, WT and spf-ash mice had reduced CPS1 and OTC enzyme activities, and, unlike WT, spf-ash mice failed to increase ureagenesis. Depression of urea cycle function was seen in liver amino acid analysis, with reductions seen in aspartate, ornithine and arginine during infection. In conclusion, we developed a model system of acute metabolic decompensation due to infection in a mouse model of a UCD. In addition, we have identified metabolic perturbations during infection in the spf-ash mice, including a reduction of urea cycle intermediates. This model of acute metabolic decompensation with HA due to infection in UCD serves as a platform for exploring biochemical perturbations and the efficacy of treatments, and could be adapted to explore acute decompensation in other types of inborn errors of metabolism.
C1 [McGuire, Peter J.; Tarasenko, Tatiana N.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Wang, Tony; Levy, Ezra; Diaz, George A.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Zerfas, Patricia M.] NIH, Off Res Serv, Div Vet Resources, Bethesda, MD 20892 USA.
[Moran, Thomas] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA.
[Lee, Hye Seung] Univ S Florida, Dept Pediat, Tampa, FL 33620 USA.
[Bequette, Brian J.] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA.
RP McGuire, PJ (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM peter.mcguire@nih.gov
FU National Institutes of Health; Children's Health Research Center at
Mount Sinai School of Medicine [K12 HD052890]
FX This work was supported by the intramural program at the National
Institutes of Health (P.J.M.) and the Children's Health Research Center
(K12 HD052890) at Mount Sinai School of Medicine (P.J.M.).
NR 30
TC 5
Z9 5
U1 0
U2 2
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 1754-8403
EI 1754-8411
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD FEB
PY 2014
VL 7
IS 2
BP 205
EP 213
DI 10.1242/dmm.013003
PG 9
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA AJ4CY
UT WOS:000337619300007
PM 24271778
ER
PT J
AU Fero, K
Bergeron, SA
Horstick, EJ
Codore, H
Li, GH
Ono, F
Dowling, JJ
Burgess, HA
AF Fero, Kandice
Bergeron, Sadie A.
Horstick, Eric J.
Codore, Hiba
Li, Grace H.
Ono, Fumihito
Dowling, James J.
Burgess, Harold A.
TI Impaired embryonic motility in dusp27 mutants reveals a developmental
defect in myofibril structure
SO DISEASE MODELS & MECHANISMS
LA English
DT Article
DE Zebrafish; dusp27; Motility; Myofibrillogenesis; Muscle
ID DUAL-SPECIFICITY PHOSPHATASES; ZEBRAFISH EMBRYO; GENE-EXPRESSION;
ACETYLCHOLINE-RECEPTORS; REGULATED GENES; IDENTIFICATION; MUTAGENESIS;
PROTEIN; BEHAVIORS; INHIBITOR
AB An essential step in muscle fiber maturation is the assembly of highly ordered myofibrils that are required for contraction. Much remains unknown about the molecular mechanisms governing the formation of the contractile apparatus. We identified an early embryonic motility mutant in zebrafish caused by integration of a transgene into the pseudophosphatase dual specificity phosphatase 27 (dusp27) gene. dusp27 mutants exhibit near complete paralysis at embryonic and larval stages, producing extremely low levels of spontaneous coiling movements and a greatly diminished touch response. Loss of dusp27 does not prevent somitogenesis but results in severe disorganization of the contractile apparatus in muscle fibers. Sarcomeric structures in mutants are almost entirely absent and only rare triads are observed. These findings are the first to implicate a functional role of dusp27 as a gene required for myofiber maturation and provide an animal model for analyzing the mechanisms governing myofibril assembly.
C1 [Fero, Kandice; Bergeron, Sadie A.; Horstick, Eric J.; Codore, Hiba; Li, Grace H.; Burgess, Harold A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, Bethesda, MD 20892 USA.
[Dowling, James J.] Univ Michigan, Dept Pediat, Med Ctr, Ann Arbor, MI 48109 USA.
[Horstick, Eric J.; Dowling, James J.] Univ Michigan, Dept Neurol, Med Ctr, Ann Arbor, MI 48109 USA.
[Dowling, James J.] Univ Michigan, Dept Neurosci, Med Ctr, Ann Arbor, MI 48109 USA.
[Ono, Fumihito] NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, Rockville, MD 20852 USA.
[Dowling, James J.] Hosp Sick Children, Div Neurol, Toronto, ON M5G 1X8, Canada.
[Dowling, James J.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.
[Dowling, James J.] Univ Toronto, Dept Paediat, Toronto, ON M5G 1X8, Canada.
[Dowling, James J.] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1X8, Canada.
RP Burgess, HA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, Bethesda, MD 20892 USA.
EM burgessha@mail.nih.gov
RI Burgess, Harold/B-8474-2015;
OI Burgess, Harold/0000-0003-1966-7801; Bergeron, Sadie/0000-0002-1238-8730
FU NICHD; NIAAA; National Institutes of Health [1K08AR054835, T32 NS007222]
FX This work was supported by the Intramural Research Programs of the NICHD
(H.A.B.) and of the NIAAA (F.O.), and National Institutes of Health
grants 1K08AR054835 (J.J.D.) and T32 NS007222 ( E.J.H.).
NR 62
TC 1
Z9 1
U1 0
U2 2
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 1754-8403
EI 1754-8411
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD FEB
PY 2014
VL 7
IS 2
BP 289
EP 298
DI 10.1242/dmm.013235
PG 10
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA AJ4CY
UT WOS:000337619300016
PM 24203884
ER
PT J
AU Glasgow, RE
Strycker, LA
King, DK
Toobert, DJ
AF Glasgow, Russell E.
Strycker, Lisa A.
King, Diane K.
Toobert, Deborah J.
TI Understanding Who Benefits at Each Step in an Internet-Based Diabetes
Self-Management Program: Application of a Recursive Partitioning
Approach
SO MEDICAL DECISION MAKING
LA English
DT Article
DE diabetes self-management; interactive media; computer; prediction;
health literacy; numeracy; Latino
ID HEALTH-CARE SETTINGS; PHYSICAL-ACTIVITY; SUPPORT PROGRAM; OLDER-ADULTS;
OUTCOMES; INTERVENTIONS; TRIAL; SCALE; RISK; RECRUITMENT
AB Background. Efforts to predict success in chronic disease management programs have been generally unsuccessful. Objective. To identify patient subgroups associated with success at each of 6 steps in a diabetes self-management (DSM) program. Design. Using data from a randomized trial, recursive partitioning with signal detection analysis was used to identify subgroups associated with 6 sequential steps of program success: agreement to participate, completion of baseline, initial website engagement, 4-month behavior change, later engagement, and longer-term maintenance. Setting. The study was conducted in 5 primary care clinics within Kaiser Permanente Colorado. Patients. Different numbers of patients participated in each step, including 2076, 544, 270, 219, 127, and 89. All measures available were used to address success at each step. Intervention. Participants were randomized to receive either enhanced usual care or 1 of 2 Internet-based DSM programs: 1) self-administered, computer-assisted self-management and 2) the self-administered program with the addition of enhanced social support. Measurements. Two sets of potential predictor variables and 6 dichotomous outcomes were created. Results. Signal detection analysis differentiated successful and unsuccessful subgroups at all but the final step. Different patient subgroups were associated with success at these different steps. Demographic factors (education, ethnicity, income) were associated with initial participation but not with later steps, and the converse was true of health behavior variables. Limitations. Analyses were limited to one setting, and the sample sizes for some of the steps were modest. Conclusions. Signal detection and recursive partitioning methods may be useful for identifying subgroups that are more or less successful at different steps of intervention and may aid in understanding variability in outcomes.
C1 [Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
[Strycker, Lisa A.; Toobert, Deborah J.] Oregon Res Inst, Eugene, OR 97403 USA.
[King, Diane K.] Univ Alaska Anchorage, Anchorage, AK USA.
RP Glasgow, RE (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 6144, Rockville, MD 20852 USA.
EM glasgowre@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
[DK35524]
FX Received 20 August 2012 from Implementation Science, Division of Cancer
Control and Population Science, National Cancer Institute, Rockville,
Maryland (REG); Oregon Research Institute, Eugene, Oregon (LAS, DJT);
and University of Alaska, Anchorage, Alaska (DKK). This study was
supported by grant DK35524 from the National Institute of Diabetes and
Digestive and Kidney Diseases. Revision accepted for publication 22 June
2013.
NR 50
TC 4
Z9 4
U1 3
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-989X
EI 1552-681X
J9 MED DECIS MAKING
JI Med. Decis. Mak.
PD FEB
PY 2014
VL 34
IS 2
BP 180
EP 191
DI 10.1177/0272989X13498156
PG 12
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA AI8QH
UT WOS:000337185600006
PM 23913917
ER
PT J
AU Byington, CL
Higgins, S
Kaskel, FJ
Purucker, M
Davis, JM
Smoyer, WE
AF Byington, Carrie L.
Higgins, Sarah
Kaskel, Fredrick J.
Purucker, Mary
Davis, Jonathan M.
Smoyer, William E.
TI The CTSA Mentored Career Development Program: Supporting the Careers of
Child Health Investigators
SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE
LA English
DT Article
DE Clinical and Translational Science Award; education; child health; KL2
program; K12 program; Institutional Career Development Award
ID TRANSLATIONAL SCIENCE; SCIENTISTS
AB Training translational scientists is a priority of the Clinical and Translational Science Award (CTSA) consortium. Objectives: 1) Describe the landscape of CTSA Mentored Research Career Development Awards (CDA) and 2) evaluate participation and outcomes of child health investigators in these programs. Design: Survey of the CTSA Child Health Oversight Committee (CC-CHOC) and review of nonresponders' CTSA Websites. Results: Thirty-two of 53 CC-CHOC members (60%) responded and all nonresponder Websites were reviewed. Institutions supported 1,166 CDA positions from 2006 to 2011, with 134 awarded to child health investigators (11.5%). Respondents reported a mean of 29.8 KL2 positions (95% CI 17.5-42.2) during their award period, with a mean of 2.8 (95% CI 1.8-3.8) awarded to child health investigators. The proportion of child health awardees varied from 0% to 50% across institutions. We identified 45 subsequent National Institutes of Health (NIH) awards to the 134 child health investigators (34%). Conclusions: The CTSA program contributes substantially to training the next generation of translational investigators. One-third of child health investigators obtained subsequent NIH awards in the short follow-up period demonstrating success of the CTSA CDA programs. Child health investigators are represented variably across the consortium. Pediatric institutions can partner with the CTSA program to further support training child health investigators.
C1 [Byington, Carrie L.] Univ Utah, Hlth Sci Ctr, Utah Ctr Clin & Translat Sci, Salt Lake City, UT 84112 USA.
[Byington, Carrie L.] Univ Utah, Hlth Sci Ctr, Dept Pediat, Salt Lake City, UT USA.
[Higgins, Sarah; Smoyer, William E.] Ohio State Univ, Ctr Clin & Translat Res, Nationwide Childrens Hosp, Ctr Clin & Translat Sci,Res Inst, Columbus, OH 43210 USA.
[Kaskel, Fredrick J.] Albert Einstein Coll Med, Einstein Montefiore Inst Clin & Translat Res, New York, NY USA.
[Kaskel, Fredrick J.] Albert Einstein Coll Med, Dept Pediat, New York, NY USA.
[Purucker, Mary] NIH, Clin & Translat Sci Awards Program, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Davis, Jonathan M.] Tufts Med Ctr, Floating Hosp Children, Dept Pediat, Boston, MA USA.
[Davis, Jonathan M.] Tufts Med Ctr, Floating Hosp Children, Tufts Clin Translat Sci Inst, Boston, MA USA.
RP Byington, CL (reprint author), Univ Utah, Hlth Sci Ctr, Utah Ctr Clin & Translat Sci, Salt Lake City, UT 84112 USA.
EM Carrie.byington@hsc.utah.edu
OI Byington, Carrie/0000-0002-7350-9495
FU National Center for Research Resources; National Center for Advancing
Translational Sciences, National Institutes of Health [8UL1TR000105];
NIH [UL1TR000090-15, 3UL1RR025750-0255, UL1 RR025752]; University of
Utah, NIH [8UL1TR000105]; Ohio State University, NIH [UL1TR000090];
Albert Einstein College of Medicine [3UL1RR025750]; Tufts Medical
Center, NIH [UL1 RR025752]
FX This work was supported by the National Center for Research Resources
and the National Center for Advancing Translational Sciences, National
Institutes of Health, through Grant 8UL1TR000105 (formerly UL1RR025764)
and NIH awards UL1TR000090-15, 3UL1RR025750-0255, and UL1 RR025752. The
authors acknowledge CTSA support to their institutions through the
following grants: University of Utah, NIH 8UL1TR000105; The Ohio State
University, NIH UL1TR000090; Albert Einstein College of Medicine,
3UL1RR025750; and Tufts Medical Center, NIH UL1 RR025752. The CTSA
Consortium Publications Committee approved the manuscript on February
19, 2013.
NR 11
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1752-8054
EI 1752-8062
J9 CTS-CLIN TRANSL SCI
JI CTS-Clin. Transl. Sci.
PD FEB
PY 2014
VL 7
IS 1
BP 44
EP 47
DI 10.1111/cts.12122
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AA9VE
UT WOS:000331440300013
PM 24528899
ER
PT J
AU De Groot, AS
Moise, L
Liu, R
Gutierrez, AH
Terry, F
Koita, OA
Ross, TM
Martin, W
AF De Groot, Anne S.
Moise, Lenny
Liu, Rui
Gutierrez, Andres H.
Terry, Frances
Koita, Ousmane A.
Ross, Ted M.
Martin, William
TI Cross-conservation of T-cell epitopes Now even more relevant to (H7N9)
influenza vaccine design
SO HUMAN VACCINES & IMMUNOTHERAPEUTICS
LA English
DT Editorial Material
DE H7N9; H1N1; avian-origin; influenza; genome; recombinant protein;
hemagglutinin; cell-mediated immunity; T-cell epitope; T cell; CD4+T
cell; T helper
ID VIRUS-LIKE PARTICLE; SEASONAL INFLUENZA; A VIRUS; HUMAN INFECTION;
ORIGIN; MICE; RESPONSES; A(H7N9); FERRETS; TRANSMISSION
C1 [De Groot, Anne S.; Moise, Lenny; Liu, Rui; Gutierrez, Andres H.] Univ Rhode Isl, Inst Immunol & Informat, Providence, RI 02908 USA.
[De Groot, Anne S.; Moise, Lenny; Terry, Frances; Martin, William] EpiVax Inc, Providence, RI USA.
[Koita, Ousmane A.] Univ Bamako, Lab Appl Mol Biol, Bamako, Mali.
[Koita, Ousmane A.] Univ Sci Tech & Technol Bamako, Inst Natl Malad Infect & Allerg, Ctr Rech & Format VIH Sida & Tuberculose, Project SEREFO NIAID, Bamako, Mali.
[Ross, Ted M.] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL USA.
RP De Groot, AS (reprint author), Univ Rhode Isl, Inst Immunol & Informat, 825 Chalkstone Ave, Providence, RI 02908 USA.
EM AnnieD@EpiVax.com
RI De Groot, Anne/B-6221-2013
OI De Groot, Anne/0000-0001-5911-1459
NR 50
TC 15
Z9 15
U1 0
U2 8
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2164-5515
EI 2164-554X
J9 HUM VACC IMMUNOTHER
JI Human Vaccines Immunother.
PD FEB
PY 2014
VL 10
IS 2
BP 256
EP 262
DI 10.4161/hv.28135
PG 7
WC Biotechnology & Applied Microbiology; Immunology
SC Biotechnology & Applied Microbiology; Immunology
GA AI1YV
UT WOS:000336652500010
PM 24525618
ER
PT J
AU Woo, EJ
Winiecki, SK
Ou, AC
AF Woo, Emily Jane
Winiecki, Scott K.
Ou, Alan C.
TI Motor palsies of cranial nerves (excluding VII) after vaccination
Reports to the US Vaccine Adverse Event Reporting System
SO HUMAN VACCINES & IMMUNOTHERAPEUTICS
LA English
DT Article
DE vaccine; cranial nerve palsy; ptosis; disconjugate gaze; adverse event;
postmarketing safety surveillance
ID ATTENUATED INFLUENZA VACCINE; BELLS-PALSY; POSTMARKETING EVALUATION;
UNITED-STATES; SAFETY; H1N1; VAERS; AGE
AB We reviewed cranial nerve palsies, other than VII, that have been reported to the US Vaccine Adverse Event Reporting System (VAERS). We examined patterns for differences in vaccine types, seriousness, age, and clinical characteristics. We identified 68 reports of cranial nerve palsies, most commonly involving the oculomotor (III), trochlear (IV), and abducens (VI) nerves. Isolated cranial nerve palsies, as well as palsies occurring as part of a broader clinical entity, were reported. Forty reports (59%) were classified as serious, suggesting that a cranial nerve palsy may sometimes be the harbinger of a broader and more ominous clinical entity, such as a stroke or encephalomyelitis. There was no conspicuous clustering of live vs. inactivated vaccines. The patient age range spanned the spectrum from infants to the elderly. Independent data may help to clarify whether, when, and to what extent the rates of cranial nerve palsies following particular vaccines may exceed background levels.
C1 [Woo, Emily Jane; Winiecki, Scott K.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Ou, Alan C.] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Woo, EJ (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
EM jane.woo@fda.hhs.gov
OI Winiecki, Scott/0000-0003-4912-4621
NR 23
TC 2
Z9 2
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2164-5515
EI 2164-554X
J9 HUM VACC IMMUNOTHER
JI Human Vaccines Immunother.
PD FEB
PY 2014
VL 10
IS 2
BP 301
EP 305
DI 10.4161/hv.27032
PG 5
WC Biotechnology & Applied Microbiology; Immunology
SC Biotechnology & Applied Microbiology; Immunology
GA AI1YV
UT WOS:000336652500014
PM 24231288
ER
PT J
AU Takeshita, J
Mohler, ER
Krishnamoorthy, P
Moore, J
Rogers, WT
Zhang, LF
Gelfand, JM
Mehta, NN
AF Takeshita, Junko
Mohler, Emile R., III
Krishnamoorthy, Parasuram
Moore, Jonni
Rogers, Wade T.
Zhang, Lifeng
Gelfand, Joel M.
Mehta, Nehal N.
TI Endothelial Cell-, Platelet-, and Monocyte/Macrophage-Derived
Microparticles are Elevated in Psoriasis Beyond Cardiometabolic Risk
Factors
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE atherosclerosis; inflammation; microparticles endothelium; platelets;
psoriasis; risk factor
ID HUMAN ATHEROSCLEROTIC PLAQUES; CIRCULATING MICROPARTICLES;
MYOCARDIAL-INFARCTION; DIABETES-MELLITUS; INFLAMMATION; DISEASES;
PECAM-1
AB Background-Psoriasis, especially when severe, is a risk factor for cardiometabolic disease beyond traditional risk factors. The mechanism of atherogenesis in psoriasis remains unknown. Cell membrane vesicles (ie, microparticles), released upon cell activation or apoptosis, have recently been associated with cardiometabolic disease and may play a pathogenic role. Microparticle levels, particularly from endothelial cells and platelets, are elevated in patients with cardiovascular disorders, metabolic syndrome, other inflammatory diseases, autoimmune conditions, and have been shown to be predictive of cardiovascular outcomes.
Methods and Results-Concentrations of microparticles with positive expression for any of 7 cell surface markers (Annexin V, CD3, CD31, CD41a, CD64, CD105, and CD144) were measured in blood samples from psoriasis patients (n=53) and control subjects without psoriasis (n=41). Platelet-free plasma was separated from whole blood by one-step centrifugation for microparticle analysis. Microparticles were fluorescently labeled and characterized by flow cytometry. Higher concentrations of CD105 (5.5/mu L versus 2.5/mu L, P<0.001), CD31 (31/mu L versus 18/mu L, P=0.002), CD41a (50/mu L versus 22/mu L, P<0.001), and CD64 (5.0/mu L versus 4.1/mu L, P=0.02) singly positive microparticles corresponding to endothelial cell-, platelet-, and monocyte/macrophage-derived microparticles, respectively, were found in psoriasis patients compared with controls. These differences persisted after adjustment for traditional cardiometabolic risk factors including body mass index.
Conclusions-Increased microparticle concentrations, independent of cardiometabolic risk factors, in patients with psoriasis suggest that the presence of increased endothelial cell, platelet, and monocyte/macrophage activation with cell turnover may contribute to the heightened atherogenesis associated with psoriasis.
C1 [Mohler, Emile R., III] Univ Penn, Perelman Sch Med, Sect Vasc Med, Philadelphia, PA 19104 USA.
[Mohler, Emile R., III; Zhang, Lifeng; Mehta, Nehal N.] Univ Penn, Perelman Sch Med, Dept Med, Div Cardiovasc Dis, Philadelphia, PA 19104 USA.
[Takeshita, Junko; Gelfand, Joel M.] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA.
[Moore, Jonni; Rogers, Wade T.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Krishnamoorthy, Parasuram] Englewood Hosp & Med Ctr, Englewood, NJ USA.
[Mehta, Nehal N.] NHLBI, Sect Inflammat & Cardiometab Dis, Bethesda, MD USA.
RP Mehta, NN (reprint author), NHLBI, Sect Inflammat & Cardiometab Dis, Bldg 10, Bethesda, MD USA.
EM nehal.mehta@nih.gov
OI Krishnamoorthy, Parasuram/0000-0002-4560-7346
FU Intramural Research Program at the NIH [T32 GM 075766-6]; National
Psoriasis Foundation Fellowship Award; Dermatology Foundation Career
Development Award; National Institute of Arthritis and Musculoskeletal
and Skin Diseases [K24-AR064310]; National Heart Lung and Blood
Institute [R01-HL111293]
FX This work was partly funded by a grant from the Intramural Research
Program at the NIH (Mehta), Training Grant T32 GM 075766-6 (Takeshita),
a National Psoriasis Foundation Fellowship Award (Takeshita), a
Dermatology Foundation Career Development Award (Takeshita), a
K24-AR064310 grant from the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (Gelfand), and a R01-HL111293 grant
from the National Heart Lung and Blood Institute.
NR 33
TC 14
Z9 15
U1 2
U2 7
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 2014
VL 3
IS 1
AR e000507
DI 10.1161/JAHA.113.000507
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AI3VZ
UT WOS:000336794500046
PM 24584739
ER
PT J
AU Jelovsek, JE
Chagin, K
Brubaker, L
Rogers, RG
Richter, HE
Arya, L
Barber, MD
Shepherd, JP
Nolen, TL
Norton, P
Sung, V
Menefee, S
Siddiqui, N
Meikle, SF
Kattan, MW
AF Jelovsek, J. Eric
Chagin, Kevin
Brubaker, Linda
Rogers, Rebecca G.
Richter, Holly E.
Arya, Lily
Barber, Matthew D.
Shepherd, Jonathan P.
Nolen, Tracy L.
Norton, Peggy
Sung, Vivian
Menefee, Shawn
Siddiqui, Nazema
Meikle, Susan F.
Kattan, Michael W.
CA Pelvic Floor Disorders Network
TI A Model for Predicting the Risk of De Novo Stress Urinary Incontinence
in Women Undergoing Pelvic Organ Prolapse Surgery
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID REDUCTION EFFORTS CARE; FREE VAGINAL TAPE; ABDOMINAL SACROCOLPOPEXY;
NOMOGRAM; REPAIR; VALIDATION; TRIAL; RECURRENCE; COLPOPEXY; DESIGN
AB OBJECTIVE: To construct and validate a prediction model for estimating the risk of de novo stress urinary incontinence (SUI) after vaginal pelvic organ prolapse (POP) surgery and compare it with predictions using preoperative urinary stress testing and expert surgeons' predictions.
MATERIALS AND METHODS: Using the data set (n=457) from the Outcomes Following Vaginal Prolapse Repair and Midurethral Sling trial, a model using 12 clinical preoperative predictors of de novo SUI was constructed. De novo SUI was determined by Pelvic Floor Distress Inventory responses through 12 months postoperatively. After fitting the multivariable logistic regression model using the best predictors, the model was internally validated with 1,000 bootstrap samples to obtain bias-corrected accuracy using a concordance index. The model's predictions were also externally validated by comparing findings against actual outcomes using Colpopexy and Urinary Reduction Efforts trial patients (n=316). The final model's performance was compared with experts using a test data set of 32 randomly chosen Outcomes Following Vaginal Prolapse Repair and Midurethral Sling trial patients through comparison of the model's area under the curve against: 1) 22 experts' predictions; and 2) preoperative prolapse reduction stress testing.
RESULTS: A model containing seven predictors discriminated between de novo SUI status (concordance index 0.73, 95% confidence interval [CI] 0.65-0.80) in Outcomes Following Vaginal Prolapse Repair and Midurethral Sling participants and outperformed expert clinicians (area under the curve 0.72 compared with 0.62, P<.001) and preoperative urinary stress testing (area under the curve 0.72 compared with 0.54, P<.001). The concordance index for Colpopexy and Urinary Reduction Efforts trial participants was 0.62 (95% CI 0.56-0.69).
CONCLUSION: This individualized prediction model for de novo SUI after vaginal POP surgery is valid and outperforms preoperative stress testing, prediction by experts, and preoperative reduction cough stress testing. An online calculator is provided for clinical use.
C1 Cleveland Clin, Obstet Gynecol & Womens Hlth Inst, Cleveland, OH 44195 USA.
[Jelovsek, J. Eric] Cleveland Clin, Cleveland, OH 44195 USA.
Loyola Univ, Stritch Sch Med, Dept Obstet & Gynecol & Urol, Chicago, IL 60611 USA.
Univ New Mexico, Hlth Sci Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA.
Univ New Mexico, Hlth Sci Ctr, Dept Surg, Albuquerque, NM 87131 USA.
Univ Alabama Birmingham, Dept Obstet, Birmingham, AL USA.
Univ Alabama Birmingham, Dept Gynecol, Birmingham, AL USA.
Univ Penn, Philadelphia, PA 19104 USA.
Univ Utah, Salt Lake City, UT USA.
Brown Univ, Women & Infants Hosp, Providence, RI USA.
Kaiser Permanente, San Diego, CA USA.
Duke Univ, Med Ctr, Durham, NC USA.
Univ Pittsburgh, Med Ctr, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
RTI Int, Res Triangle Pk, NC USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Jelovsek, JE (reprint author), Cleveland Clin, 9500 Euclid Ave A81, Cleveland, OH 44195 USA.
EM jelovsj@ccf.org
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [2U01HD41249, 2U10 HD41250, 2U10 HD41261, 2U10 HD41267, 1U10
HD54136, 1U10 HD54214, 1U10 HD54215, 1U10 HD54241, U10 HD069013, U10
HD069025, U10 HD069010, U01 HD069031]; National Institutes of Health
Office of Research on Women's Health
FX Supported by grants from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (2U01HD41249, 2U10 HD41250, 2U10
HD41261, 2U10 HD41267, 1U10 HD54136, 1U10 HD54214, 1U10 HD54215, 1U10
HD54241, U10 HD069013, U10 HD069025, U10 HD069010, U10 HD069010, and U01
HD069031) and the National Institutes of Health Office of Research on
Women's Health.
NR 20
TC 13
Z9 13
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
EI 1873-233X
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD FEB
PY 2014
VL 123
IS 2
BP 279
EP 287
DI 10.1097/AOG.0000000000000094
PN 1
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AI4AY
UT WOS:000336808800009
PM 24402598
ER
PT J
AU Pinar, H
Goldenberg, RL
Koch, MA
Heim-Hall, J
Hawkins, HK
Shehata, B
Abramowsky, C
Parker, CB
Dudley, DJ
Silver, RM
Stoll, B
Carpenter, M
Saade, G
Moore, J
Conway, D
Varner, MW
Hogue, CJR
Coustan, DR
Sbrana, E
Thorsten, V
Willinger, M
Reddy, UM
AF Pinar, Halit
Goldenberg, Robert L.
Koch, Matthew A.
Heim-Hall, Josefine
Hawkins, Hal K.
Shehata, Bahig
Abramowsky, Carlos
Parker, Corette B.
Dudley, Donald J.
Silver, Robert M.
Stoll, Barbara
Carpenter, Marshall
Saade, George
Moore, Janet
Conway, Deborah
Varner, Michael W.
Hogue, Carol J. R.
Coustan, Donald R.
Sbrana, Elena
Thorsten, Vanessa
Willinger, Marian
Reddy, Uma M.
TI Placental Findings in Singleton Stillbirths
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID PERINATAL AUTOPSY; RISK-FACTORS; POSTMORTEM EXAMINATION; FETAL;
CLASSIFICATION; INFECTION; DEATH; OUTCOMES; BIRTH; RATES
AB OBJECTIVE: To compare placental lesions for stillbirth cases and live birth controls in a population-based study.
METHODS: Pathologic examinations were performed on placentas from singleton pregnancies using a standard protocol. Data were analyzed overall and within gestational age groups at delivery.
RESULTS: Placentas from 518 stillbirths and 1,200 live births were studied. Single umbilical artery was present in 7.7% of stillbirths and 1.7% of live births, velamentous cord insertion was present in 5% of stillbirths and 1.1% of live births, diffuse terminal villous immaturity was present in 10.3% of stillbirths and 2.3% of live births, inflammation (eg, acute chorioamnionitis of placental membranes) was present in 30.4% of stillbirths and 12% of live births, vascular degenerative changes in chorionic plate were present in 55.7% of stillbirths and 0.5% of live births, retroplacental hematoma was present in 23.8% of stillbirths and 4.2% of live births, intraparenchymal thrombi was present in 19.7% of stillbirths and 13.3% of live births, parenchymal infarction was present in 10.9% of stillbirths and 4.4% of live births, fibrin deposition was present in 9.2% of stillbirths and 1.5% of live births, fetal vascular thrombi was present in 23% of stillbirths and 7% of live births, avascular villi was present in 7.6% of stillbirths and 2.0% of live births, and hydrops was present in 6.4% of stillbirths and 1.0% of live births. Among stillbirths, inflammation and retroplacental hematoma were more common in placentas from early deliveries, whereas thrombotic lesions were more common in later gestation. Inflammatory lesions were especially common in early live births.
CONCLUSIONS: Placental lesions were highly associated with stillbirth compared with live births. All lesions associated with stillbirth were found in live births but often with variations by gestational age at delivery. Knowledge of lesion prevalence within gestational age groups in both stillbirths and live birth controls contributes to an understanding of the association between placental abnormality and stillbirth.
C1 Brown Univ, Warren Alpert Med Sch, Providence, RI 02905 USA.
Columbia Univ, Sch Med, New York, NY USA.
RTI Int, Durham, NC USA.
Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
Univ Texas Med Branch, Galveston, TX 77555 USA.
Emory Univ, Atlanta, GA 30322 USA.
Univ Utah, Sch Med, Salt Lake City, UT USA.
Tufts Univ, Med Ctr, Boston, MA 02111 USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Pinar, H (reprint author), Brown Univ, Women & Infants Hosp, Div Perinatal Pathol, Warren Alpert Med Sch, 101 Dudley St, Providence, RI 02905 USA.
EM hpinar@brown.edu
RI Varner, Michael/K-9890-2013
OI Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD45925, HD45944, HD45952, HD45953, HD45954]
FX Supported by grants (HD45925, HD45944, HD45952, HD45953, HD45954, and
HD45925) from the Eunice Kennedy Shriver National Institute of Child
Health and Human Development.
NR 29
TC 38
Z9 39
U1 1
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
EI 1873-233X
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD FEB
PY 2014
VL 123
IS 2
BP 325
EP 336
DI 10.1097/AOG.0000000000000100
PN 1
PG 12
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AI4AY
UT WOS:000336808800015
PM 24402599
ER
PT J
AU Kawabata, S
Chiang, CT
Tsurutani, J
Shiga, H
Arwood, ML
Komiya, T
Gills, JJ
Memmott, RM
Dennis, PA
AF Kawabata, Shigeru
Chiang, Chun-Te
Tsurutani, Junji
Shiga, Hideaki
Arwood, Matthew L.
Komiya, Takefumi
Gills, Joell J.
Memmott, Regan M.
Dennis, Phillip A.
TI Rapamycin downregulates thymidylate synthase and potentiates the
activity of pemetrexed in non-small cell lung cancer
SO ONCOTARGET
LA English
DT Article
DE Rapamycin; Pemetrexed; Drug synergy; mTOR; Thymidylate Synthase; Lung
Cancer
ID PHARMACOLOGICAL INHIBITION; CHEMOTHERAPY; CYTOTOXICITY; EXPRESSION;
SENSITIVITY; COMBINATION; ACTIVATION; RESISTANCE; KINASE; NSCLC
AB Non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancer cases, and almost half of newly diagnosed patients have metastatic disease. Pemetrexed is a widely used drug for NSCLC and inhibits several folate-dependent enzymes including thymidylate synthase (TS). Increased expression of TS confers resistance to pemetrexed in vitro and predicts poor response to pemetrexed. Rapamycin is an mTOR inhibitor and suppresses cap-dependent synthesis of specific mRNA species. Here, we show that the combination of rapamycin and pemetrexed synergistically inhibits proliferation of NSCLC cells. Although pemetrexed as a single agent induced TS, pretreatment with rapamycin suppressed pemetrexed-induced TS expression. In vivo, the combination of rapamycin and pemetrexed inhibited growth of NSCLC xenografts, which correlated with decreased mTOR activity and suppression of pemetrexed-induced TS expression. The ability of rapamycin to enhance the efficacy of pemetrexed and prevent TS expression has implications for the design of Phase I and/or Phase II NSCLC clinical trials with mTOR inhibitors in combination with pemetrexed.
C1 [Kawabata, Shigeru; Arwood, Matthew L.; Gills, Joell J.; Memmott, Regan M.; Dennis, Phillip A.] Johns Hopkins Bayview Med Ctr, Dept Oncol, Baltimore, MD 21224 USA.
[Chiang, Chun-Te; Tsurutani, Junji; Shiga, Hideaki; Komiya, Takefumi] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Dennis, PA (reprint author), Johns Hopkins Bayview Med Ctr, Dept Oncol, Baltimore, MD 21224 USA.
EM pdennis@jhmi.edu
OI Shiga, Hideaki/0000-0001-7218-154X
FU Intramural Research Program of the NIH, Center for Cancer Research,
National Cancer Institute; Open Access Promotion Fund of the Johns
Hopkins University Libraries
FX This research was supported by the Intramural Research Program of the
NIH, Center for Cancer Research, National Cancer Institute. The content
of this publication does not necessarily reflect the views or policies
of the Department of Health and Human Services, nor does mention of
trade names, commercial products, or organization imply endorsement by
the United States Government. Publication of this article was funded in
part by the Open Access Promotion Fund of the Johns Hopkins University
Libraries.
NR 30
TC 8
Z9 8
U1 0
U2 3
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 2014
VL 5
IS 4
BP 1062
EP 1070
PG 9
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AI6EA
UT WOS:000336962300019
PM 24658085
ER
PT J
AU Casady, M
Faia, L
Nazemzadeh, M
Nussenblatt, R
Chan, CC
Sen, HN
AF Casady, Megan
Faia, Lisa
Nazemzadeh, Maryam
Nussenblatt, Robert
Chan, Chi-Chao
Sen, H. Nida
TI FUNDUS AUTOFLUORESCENCE PATTERNS IN PRIMARY INTRAOCULAR LYMPHOMA
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE cytokines; diagnosis; fundus autofluorescence; primary intraocular
lymphoma; primary vitreoretinal lymphoma; uveitis
ID COLLABORATIVE GROUP-REPORT
AB Purpose: To evaluate fundus autofluorescence (FAF) patterns in patients with primary intraocular (vitreoretinal) lymphoma.
Methods: Records of all patients with primary intraocular lymphoma who underwent FAF imaging at the National Eye Institute were reviewed. Fundus autofluorescence patterns were evaluated with respect to clinical disease status and the findings on fluorescein angiography and spectral-domain optical coherence tomography.
Results: There were 18 eyes (10 patients) with primary intraocular lymphoma that underwent FAF imaging. Abnormal autofluorescence in the form of granular hyperautofluorescence and hypoautofluorescence was seen in 11 eyes (61%), and blockage by mass lesion was seen in 2 eyes (11%). All eyes with granular pattern on FAF had active primary intraocular lymphoma at the time of imaging, but there were 5 eyes with unremarkable FAF, which were found to have active lymphoma. The most common pattern on fluorescein angiography was hypofluorescent round spots with a "leopard spot" appearance (43%). These hypofluorescent spots on fluorescein angiography correlated with hyperautofluorescent spots on FAF in 5 eyes (36%) (inversion of FAF). Nodular hyperreflective spots at the level of retinal pigment epithelium on optical coherence tomography were noted in 43% of eyes. The hyperautofluorescent spots on FAF correlated with nodular hyperreflective spots on optical coherence tomography in 6 eyes (43%).
Conclusion: Granularity on FAF was associated with active lymphoma in majority of the cases. An inversion of FAF (hyperautofluorescent spots on FAF corresponding to hypofluorescent spots on fluorescein angiography) was observed in less than half of the eyes.
C1 [Casady, Megan; Faia, Lisa; Nazemzadeh, Maryam; Nussenblatt, Robert; Chan, Chi-Chao; Sen, H. Nida] NEI, NIH, Bethesda, MD 20892 USA.
[Faia, Lisa] Associated Retinal Consultants PC, Royal Oak, MI USA.
RP Sen, HN (reprint author), NEI, NIH, 10 Ctr Dr,10-10N109, Bethesda, MD 20892 USA.
EM senh@nei.nih.gov
NR 21
TC 10
Z9 11
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD FEB
PY 2014
VL 34
IS 2
BP 366
EP 372
PG 7
WC Ophthalmology
SC Ophthalmology
GA AI6DF
UT WOS:000336959400021
PM 23958842
ER
PT J
AU Dohle, W
Leese, MP
Jourdan, FL
Major, MR
Bai, RL
Hamel, E
Ferrandis, E
Kasprzyk, PG
Fiore, A
Newman, SP
Purohit, A
Potter, BVL
AF Dohle, Wolfgang
Leese, Mathew P.
Jourdan, Fabrice L.
Major, Meriel R.
Bai, Ruoli
Hamel, Ernest
Ferrandis, Eric
Kasprzyk, Philip G.
Fiore, Ann
Newman, Simon P.
Purohit, Atul
Potter, Barry V. L.
TI Synthesis, Antitubulin, and Antiproliferative SAR of C3/C1-Substituted
Tetrahydroisoquinolines
SO CHEMMEDCHEM
LA English
DT Article
DE colchicine; microtubules; steric repulsion; tetrahydroisoquinolines;
tubulin
ID MULTITARGETED ANTITUMOR AGENTS; BREAST-CANCER CELLS; IN-VITRO;
ANTICANCER ACTIVITY; ANTIMITOTIC AGENTS; TUBULIN; VIVO; INHIBITION;
ANALOGS; DERIVATIVES
AB The syntheses and antiproliferative activities of novel substituted tetrahydroisoquinoline derivatives and their sulfamates are discussed. Biasing of conformational populations through substitution on the tetrahydroisoquinoline core at C1 and C3 has a profound effect on the antiproliferative activity against various cancer cell lines. The C3 methyl-substituted sulfamate (+/-)-7-methoxy-2-(3-methoxybenzyl)-3-methyl-6-sulfamoyloxy-1,2,3,4-tetrahydroisoquinoline (6b), for example, was found to be similar to 10-fold more potent than the corresponding non-methylated compound 7-methoxy-2-(3-methoxybenzyl)-6-sulfamoyloxy- 1,2,3,4-tetrahydroisoquinoline (4b) against DU-145 prostate cancer cells (GI(50) values: 220 nm and 2.1 mm, respectively). Such compounds were also found to be active against a drug-resistant MCF breast cancer cell line. The position and nature of substitution of the N-benzyl group in the C3-substituted series was found to have a significant effect on activity. Whereas C1 methylation has little effect on activity, introduction of C1 phenyl and C3-gem-dimethyl substituents greatly decreases antiproliferative activity. The ability of these compounds to inhibit microtubule polymerisation and to bind tubulin in a competitive manner versus colchicine confirms the mechanism of action. The therapeutic potential of a representative compound was confirmed in an in vivo multiple myeloma xenograft study.
C1 [Dohle, Wolfgang; Leese, Mathew P.; Jourdan, Fabrice L.; Major, Meriel R.; Potter, Barry V. L.] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England.
[Bai, Ruoli; Hamel, Ernest] NCI, Frederick, MD 21702 USA.
[Ferrandis, Eric] Inst Rech Henri Beaufour, F-91966 Les Ulis, France.
[Kasprzyk, Philip G.; Fiore, Ann] IPSEN, Milford, MA 01757 USA.
[Newman, Simon P.; Purohit, Atul] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London W12 0NN, England.
RP Potter, BVL (reprint author), Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England.
EM B.V.L.Potter@bath.ac.uk
FU Sterix Ltd. a member of the IPSEN Group
FX This work was supported by Sterix Ltd., a member of the IPSEN Group. We
thank Ms. Alison Smith (University of Bath) for technical support, and
the NCI DTP program for providing in vitro screening resources.
NR 32
TC 6
Z9 6
U1 0
U2 10
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1860-7179
EI 1860-7187
J9 CHEMMEDCHEM
JI ChemMedChem
PD FEB
PY 2014
VL 9
IS 2
BP 350
EP 370
DI 10.1002/cmdc.201300412
PG 21
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AI3GE
UT WOS:000336748000012
PM 24436228
ER
PT J
AU Sioka, C
Estrada-Veras, J
Maric, I
Gahl, WA
Chen, CC
AF Sioka, Chrissa
Estrada-Veras, Juvianee
Maric, Irinia
Gahl, William A.
Chen, Clara C.
TI FDG PET Images in a Patient With Erdheim-Chester Disease
SO CLINICAL NUCLEAR MEDICINE
LA English
DT Editorial Material
DE PET/CT; FDG; Erdheim-Chester disease; histiocytosis
ID IMAGING FINDINGS; INVOLVEMENT
C1 [Sioka, Chrissa; Chen, Clara C.] NHGRI, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Estrada-Veras, Juvianee; Gahl, William A.] NHGRI, Med Genet Branch, Off Clin Director, Bethesda, MD 20892 USA.
[Maric, Irinia] NIH, Hematol Sect, Dept Lab Med, Bethesda, MD 20892 USA.
RP Chen, CC (reprint author), Ctr Clin, Div Nucl Med, Dept Radiol & Imaging Sci, Bldg 10,RM 1C-459,10 Ctr Dr,MSC 1074, Bethesda, MD 20892 USA.
EM cchen1@cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 8
TC 2
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0363-9762
EI 1536-0229
J9 CLIN NUCL MED
JI Clin. Nucl. Med.
PD FEB
PY 2014
VL 39
IS 2
BP 170
EP 177
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI3DB
UT WOS:000336738100027
PM 23640213
ER
PT J
AU Pearson, MR
Derlega, VJ
Henson, JM
Holmes, KY
Ferrer, RA
Harrison, SB
AF Pearson, Matthew R.
Derlega, Valerian J.
Henson, James M.
Holmes, Karen Y.
Ferrer, Rebecca A.
Harrison, Scott B.
TI Role of Neuroticism and Coping Strategies in Psychological Reactions to
a Racist Incident Among African American University Students
SO JOURNAL OF BLACK PSYCHOLOGY
LA English
DT Article
DE discrimination; personality; coping; structural equation model; racism
ID PERCEIVED DISCRIMINATION; COLLEGE-STUDENTS; STRESS PROCESS;
MENTAL-HEALTH; PERSONALITY; RACE; COMMUNITY; SYMPTOMS; WOMEN; MODEL
AB A total of 562 African American university students provided data on individual differences in neuroticism; coping with a recent experience being the target of prejudice, racism, and/or discrimination; and psychological reactions to the incident. Higher negative affect, lower positive affect, more intrusive thoughts about the incident, and lack of forgiveness for the perpetrator were used to index distress in response to the racist incident. Using factor analyses, we determined the factor structure of the Brief COPE in our sample. Using structural equation modeling, we then examined neuroticism and each coping factor as unique predictors of reactions to the race-related incident. We documented that there were direct and indirect associations (via the selection of coping strategies) between neuroticism and the outcome measures. Neuroticism also moderated the association between particular coping strategies and reactions to the racist incident. There was also evidence for direct associations between various coping strategies and the outcome measures. The research, though preliminary, suggests the importance of neuroticism and coping strategies in understanding psychological reactions to being the target of racism.
C1 [Pearson, Matthew R.; Derlega, Valerian J.; Henson, James M.; Harrison, Scott B.] Old Dominion Univ, Norfolk, VA USA.
[Holmes, Karen Y.] Norfolk State Univ, Norfolk, VA USA.
[Ferrer, Rebecca A.] NCI, Rockville, MD USA.
RP Pearson, MR (reprint author), Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87111 USA.
EM mateo.pearson@gmail.com
NR 43
TC 1
Z9 1
U1 3
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0095-7984
EI 1552-4558
J9 J BLACK PSYCHOL
JI J. Black Psychol.
PD FEB
PY 2014
VL 40
IS 1
BP 81
EP 111
DI 10.1177/0095798412471682
PG 31
WC Psychology, Multidisciplinary
SC Psychology
GA AI0AO
UT WOS:000336508500005
ER
PT J
AU Lozito, TP
Jackson, WM
Nesti, LJ
Tuan, RS
AF Lozito, Thomas P.
Jackson, Wesley M.
Nesti, Leon J.
Tuan, Rocky S.
TI Human mesenchymal stem cells generate a distinct pericellular zone of
MMP activities via binding of MMPs and secretion of high levels of TIMPs
SO MATRIX BIOLOGY
LA English
DT Article
DE Mesenchymal stem cells (MSCs); Matrix metalloprotease (MMP); Tissue
inhibitors of metalloprotease (TIMP)
ID HUMAN BONE-MARROW; MATRIX METALLOPROTEINASES; TISSUE-INHIBITOR;
PROGENITOR CELLS; STROMAL CELLS; SKIN CARCINOGENESIS; GELATINASE-A;
DENTAL-PULP; DIFFERENTIATION; ACTIVATION
AB Mesenchymal stem cells (MSCs) are attractive candidates for inclusion in cell-based therapies by virtue of their abilities to home to wound sites. However, in-depth characterization of the specific effects of MSCs on their microenvironments is needed to realize their full therapeutic potentials. Furthermore, since MSCs of varying properties can be isolated from a diverse spectrum of tissues, a strategic and rational approach in MSC sourcing for a particular application has yet to be achieved. For example, MSCs that activate their proteolytic environments may promote tissue remodeling, while those from different tissue sources may inhibit proteases and promote tissue stabilization. This study attempts to address these issues by analyzing MSCs isolated from three adult tissue sources in terms of their effects on their proteolytic microenvironments. Human bone marrow, adipose, and traumatized muscle derived MSCs were compared in their soluble and cellular-associated MMP components and activity. For all types of MSCs, MMP activity associated with the cell surface, but activity levels and MMP profiles differed with tissue source. All MSC types bound exogenous active MMPs at their surfaces. MSCs were also able to activate exogenous proMMP-2 and proMMP-13. This is in marked contrast to the MSC soluble compartment, which strongly inhibited MMPs via endogenous TIMPs. The exact TIMP used to inhibit the exogenous MMP differed with MSC type. Thus, MSCs saturate their environment with both MMPs and TIMPs. Since they bind and activate MMPs at their surfaces, the net result is a very controlled pericellular localization of MMP activities by MSCs. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Lozito, Thomas P.; Tuan, Rocky S.] Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Ctr Cellular & Mol Engn, Pittsburgh, PA 15261 USA.
[Jackson, Wesley M.; Nesti, Leon J.] NIAMSD, Orthopaed Res Grp, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Nesti, Leon J.] Walter Reed Army Med Ctr, Dept Orthopaed & Rehabil, Washington, DC 20307 USA.
[Nesti, Leon J.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA.
RP Tuan, RS (reprint author), Ctr Cellular & Mol Engn, Dept Orthopaed Surg, 450 Technol Dr,Room 221, Pittsburgh, PA 15219 USA.
EM rst13@pitt.edu
FU Department of Defense [W81XWH-10-1-0850]; Military Amputee Research
Program at WRAMC [PO5-A011]; Commonwealth of Pennsylvania Department of
Health
FX This project was supported by grants from the Department of Defense
(W81XWH-10-1-0850), the Military Amputee Research Program at WRAMC
(PO5-A011), and the Commonwealth of Pennsylvania Dept Anent of Health.
NR 53
TC 17
Z9 17
U1 1
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0945-053X
EI 1569-1802
J9 MATRIX BIOL
JI Matrix Biol.
PD FEB
PY 2014
VL 34
BP 132
EP 143
DI 10.1016/j.matbio.2013.10.003
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AH9PD
UT WOS:000336473400014
PM 24140982
ER
PT J
AU Thurm, A
Manwaring, SS
Luckenbaugh, DA
Lord, C
Swedo, SE
AF Thurm, Audrey
Manwaring, Stacy S.
Luckenbaugh, David A.
Lord, Catherine
Swedo, Susan E.
TI Patterns of skill attainment and loss in young children with autism
SO DEVELOPMENT AND PSYCHOPATHOLOGY
LA English
DT Article
ID SPECTRUM DISORDERS; DEVELOPMENTAL REGRESSION; LANGUAGE REGRESSION; HOME
VIDEOTAPES; ONSET PATTERNS; AGE; INFANTS; COMMUNICATION; BRAIN;
RECOGNITION
AB The purpose of this study was to extend the literature on the ontogeny of autism spectrum disorder (ASD) by examining early attainment and loss of specific sociocommunicative skills in children with autism (AUT; n = 125), pervasive developmental disorder not otherwise specified (PDD-NOS; n = 42), nonspectrum developmental delays (n = 46), and typical development (n = 31). The ages of skill attainment and loss were obtained from a caregiver interview. The findings indicated that children with AUT, PDD-NOS, and developmental delays diverged from typically developing children in attainment of sociocommunicative skills early in the first year of life. Loss of at least one skill was reported in a majority of children with AUT and PDD-NOS. Significant delays in attainment of skills were also reported in children who lost skills. The wide variation in skill attainment and loss reported across children indicates that symptom onset and regression may be best represented continuously, with at least some early delay and loss present for a great majority of children with ASD.
C1 [Thurm, Audrey; Luckenbaugh, David A.; Swedo, Susan E.] NIMH, Bethesda, MD 20892 USA.
[Manwaring, Stacy S.] Univ Utah, Salt Lake City, UT 84112 USA.
[Lord, Catherine] Cornell Univ, Ithaca, NY 14853 USA.
RP Thurm, A (reprint author), NIMH, Pediat & Dev Neurosci Branch, 10 Ctr Dr,MSC 1255,Bldg 10,Room 1C250, Bethesda, MD 20892 USA.
EM athurm@mail.nih.gov
OI Manwaring, Stacy/0000-0002-0835-9398
FU Intramural NIH HHS [Z99 MH999999]
NR 53
TC 2
Z9 3
U1 6
U2 17
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0954-5794
EI 1469-2198
J9 DEV PSYCHOPATHOL
JI Dev. Psychopathol.
PD FEB
PY 2014
VL 26
IS 1
BP 203
EP 214
DI 10.1017/S0954579413000874
PG 12
WC Psychology, Developmental
SC Psychology
GA AD0UV
UT WOS:000332950500014
PM 24274034
ER
PT J
AU Guyer, AE
Benson, B
Choate, VR
Bar-Haim, Y
Perez-Edgar, K
Jarcho, JM
Pine, DS
Ernst, M
Fox, NA
Nelson, EE
AF Guyer, Amanda E.
Benson, Brenda
Choate, Victoria R.
Bar-Haim, Yair
Perez-Edgar, Koraly
Jarcho, Johanna M.
Pine, Daniel S.
Ernst, Monique
Fox, Nathan A.
Nelson, Eric E.
TI Lasting associations between early-childhood temperament and
late-adolescent reward-circuitry response to peer feedback
SO DEVELOPMENT AND PSYCHOPATHOLOGY
LA English
DT Article
ID SOCIAL-ANXIETY-DISORDER; BEHAVIORAL-INHIBITION; HUMAN STRIATUM;
CHILDREN; WITHDRAWAL; PSYCHOPATHOLOGY; SPEECH; PHOBIA; FACES; BRAIN
AB Behavioral inhibition, a temperament identifiable in infancy, is associated with heightened withdrawal from social encounters. Prior studies raise particular interest in the striatum, which responds uniquely to monetary gains in behaviorally inhibited children followed into adolescence. Although behavioral manifestations of inhibition are expressed primarily in the social domain, it remains unclear whether observed striatal alterations to monetary incentives also extend to social contexts. In the current study, imaging data were acquired from 39 participants (17 males, 22 females; ages 16-18 years) characterized since infancy on measures of behavioral inhibition. A social evaluation task was used to assess neural response to anticipation and receipt of positive and negative feedback from novel peers, classified by participants as being of high or low interest. As with monetary rewards, striatal response patterns differed during both anticipation and receipt of social reward between behaviorally inhibited and noninhibited adolescents. The current results, when combined with prior findings, suggest that early-life temperament predicts altered striatal response in both social and nonsocial contexts and provide support for continuity between temperament measured in early childhood and neural response to social signals measured in late adolescence and early adulthood.
C1 [Guyer, Amanda E.] Univ Calif Davis, Davis, CA 95618 USA.
[Benson, Brenda; Jarcho, Johanna M.; Pine, Daniel S.; Ernst, Monique; Nelson, Eric E.] NIMH, Bethesda, MD 20892 USA.
[Choate, Victoria R.] Univ Massachusetts, Boston, MA 02125 USA.
[Bar-Haim, Yair] Tel Aviv Univ, IL-69978 Tel Aviv, Israel.
[Perez-Edgar, Koraly] Penn State Univ, University Pk, PA 16802 USA.
[Fox, Nathan A.] Univ Maryland, College Pk, MD 20742 USA.
RP Guyer, AE (reprint author), Univ Calif Davis, Dept Human Ecol, Ctr Mind & Brain, 267 Cousteau Pl, Davis, CA 95618 USA.
EM aeguyer@ucdavis.edu
OI Perez-Edgar, Koraly/0000-0003-4051-9563; Jarcho,
Johanna/0000-0001-9075-6968; Nelson, Eric/0000-0002-3376-2453
FU NIMH NIH HHS [MH080076, MH074454, R00 MH080076, R01 MH074454, R01
MH094633, U01 MH074454]
NR 81
TC 20
Z9 20
U1 3
U2 21
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0954-5794
EI 1469-2198
J9 DEV PSYCHOPATHOL
JI Dev. Psychopathol.
PD FEB
PY 2014
VL 26
IS 1
BP 229
EP 243
DI 10.1017/S0954579413000941
PG 15
WC Psychology, Developmental
SC Psychology
GA AD0UV
UT WOS:000332950500016
PM 24444176
ER
PT J
AU Williams, KE
Anderton, DL
Lee, MP
Pentecost, BT
Arcaro, KF
AF Williams, Kristin E.
Anderton, Douglas L.
Lee, Maxwell P.
Pentecost, Brian T.
Arcaro, Kathleen F.
TI High-density array analysis of DNA methylation in Tamoxifen-resistant
breast cancer cell lines
SO EPIGENETICS
LA English
DT Article
DE Tamoxifen Resistance; Breast Cancer; Estrogen Receptor;
HumanMethylation450 BeadChip; methylation; ZNF350; MAGED1
ID GENE-EXPRESSION; 5-AZA-2'-DEOXYCYTIDINE; CARCINOMAS; MECHANISMS;
INDUCTION; INVASION; VARIANT
AB Roughly two-thirds of all breast cancers are ER-positive and can be treated with the antiestrogen, Tamoxifen, however resistance occurs in 33% of women who take the drug for more than 5 y. Aberrant DNA methylation, an epigenetic mechanism that alters gene expression in cancer, is thought to play a role in this resistance. To develop an understanding of Tamoxifen-resistance and identify novel pathways and targets of aberrant methylation, DNA from MCF-7 breast cancer cells and Tamoxifen-resistant derivatives, TMX2-11 and TMX2-28, were analyzed using the Illumina HumanMethylation450 BeadChip. Normalizing against MCF-7 values, ER-positive TMX2-11 had 4000 hypermethylated sites and ER-negative TMX2-28 had over 33000. Analysis of CpG sites altered in both TMX2-11 and TMX2-28 revealed that the Tamoxifen-resistant cell lines share 3000 hypermethylated and 200 hypomethylated CpGs. ZNF350 and MAGED1, two genes hypermethylated in both cell lines, were examined in greater detail. Treatment with 5-aza-2?deoxycitidine caused a significant reduction in promoter methylation of both ZNF350 and MAGED1 and a corresponding increase in expression in TMX2-28. A similar relationship between methylation and expression was not detected in TMX2-11. Our findings are indicative of the variable responses to methylation-targeted breast cancer therapy and highlight the need for biomarkers that accurately predict treatment outcome.
C1 [Williams, Kristin E.; Arcaro, Kathleen F.] Univ Massachusetts, Dept Vet & Anim Sci, Mol & Cellular Biol Grad Program, Amherst, MA 01003 USA.
[Anderton, Douglas L.] Univ S Carolina, Dept Sociol, Columbia, SC 29208 USA.
[Lee, Maxwell P.] NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
[Pentecost, Brian T.] Wadsworth Ctr, Albany, NY USA.
RP Arcaro, KF (reprint author), Univ Massachusetts, Dept Vet & Anim Sci, Mol & Cellular Biol Grad Program, Amherst, MA 01003 USA.
EM karcaro@vasci.umass.edu
FU Department of Defense CDMRP Breast Cancer Pre-doctoral grant; Avon
Foundation for Women; Rays of Hope Foundation
FX The authors would like to thank Dr John Gierthy for his generous gift of
TMX2-11 and TMX2-28. Williams KE was funded by the Department of Defense
CDMRP Breast Cancer Pre-doctoral grant. This research was supported by
grants from the Avon Foundation for Women and the Rays of Hope
Foundation to KFA.
NR 27
TC 7
Z9 7
U1 0
U2 4
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1559-2294
EI 1559-2308
J9 EPIGENETICS-US
JI Epigenetics
PD FEB 1
PY 2014
VL 9
IS 2
BP 297
EP 307
DI 10.4161/epi.27111
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AB6EK
UT WOS:000331880200014
PM 24225485
ER
PT J
AU Wu, MC
Joubert, BR
Kuan, PF
Haberg, SE
Nystad, W
Peddada, SD
London, SJ
AF Wu, Michael C.
Joubert, Bonnie R.
Kuan, Pei-fen
Haberg, Siri E.
Nystad, Wenche
Peddada, Shyamal D.
London, Stephanie J.
TI A systematic assessment of normalization approaches for the Infinium
450K methylation platform
SO EPIGENETICS
LA English
DT Article
DE association testing; cotinine exposure; genome wide methylation
profiling; normalization; reproducibility
ID DNA METHYLATION; QUANTILE NORMALIZATION; PREGNANCY; NEWBORNS; SMOKING;
CANCER
AB The Illumina Infinium HumanMethylation450 BeadChip has emerged as one of the most popular platforms for genome wide profiling of DNA methylation. While the technology is wide-spread, systematic technical biases are believed to be present in the data. For example, this array incorporates two different chemical assays, i.e., Type I and Type II probes, which exhibit different technical characteristics and potentially complicate the computational and statistical analysis. Several normalization methods have been introduced recently to adjust for possible biases. However, there is considerable debate within the field on which normalization procedure should be used and indeed whether normalization is even necessary. Yet despite the importance of the question, there has been little comprehensive comparison of normalization methods. We sought to systematically compare several popular normalization approaches using the Norwegian Mother and Child Cohort Study (MoBa) methylation data set and the technical replicates analyzed with it as a case study. We assessed both the reproducibility between technical replicates following normalization and the effect of normalization on association analysis. Results indicate that the raw data are already highly reproducible, some normalization approaches can slightly improve reproducibility, but other normalization approaches may introduce more variability into the data. Results also suggest that differences in association analysis after applying different normalizations are not large when the signal is strong, but when the signal is more modest, different normalizations can yield very different numbers of findings that meet a weaker statistical significance threshold. Overall, our work provides useful, objective assessment of the effectiveness of key normalization methods.
C1 [Wu, Michael C.; Kuan, Pei-fen] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA.
[Wu, Michael C.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Joubert, Bonnie R.; Peddada, Shyamal D.; London, Stephanie J.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Haberg, Siri E.; Nystad, Wenche] Norwegian Inst Publ Hlth, Oslo, Norway.
RP Wu, MC (reprint author), Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA.
EM mcwu@fhcrc.org; London2@niehs.nih.gov
OI London, Stephanie/0000-0003-4911-5290; Wu, Michael
C./0000-0002-3357-6570
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [Z01-ES-49019]; NIH [P30ES010126,
R01HD058008]; Norwegian Ministry of Health; Ministry of Education and
Research, NIH/NIEHS [NO-ES-75558]; NIH/NINDS [1 UO1 NS 047537-01];
Norwegian Research Council/FUGE [151918/S10]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences
(Z01-ES-49019) and NIH grants P30ES010126 and R01HD058008. The Norwegian
Mother and Child Cohort Study is supported by the Norwegian Ministry of
Health and the Ministry of Education and Research, NIH/NIEHS (contract
no NO-ES-75558), NIH/NINDS (grant no. 1 UO1 NS 047537-01), and the
Norwegian Research Council/FUGE (grant no. 151918/S10).
NR 24
TC 24
Z9 24
U1 0
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1559-2294
EI 1559-2308
J9 EPIGENETICS-US
JI Epigenetics
PD FEB 1
PY 2014
VL 9
IS 2
BP 318
EP 329
DI 10.4161/epi.27119
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AB6EK
UT WOS:000331880200016
PM 24241353
ER
PT J
AU West, RR
Hsu, AP
Holland, SM
Cuellar-Rodriguez, J
Hickstein, DD
AF West, Robert R.
Hsu, Amy P.
Holland, Steven M.
Cuellar-Rodriguez, Jennifer
Hickstein, Dennis D.
TI Acquired ASXL1 mutations are common in patients with inherited GATA2
mutations and correlate with myeloid transformation
SO HAEMATOLOGICA
LA English
DT Article
ID CHRONIC MYELOMONOCYTIC LEUKEMIA; FAMILIAL MYELODYSPLASTIC SYNDROME;
PROGNOSTIC MODEL; SPORADIC MONOCYTOPENIA; AUTOSOMAL-DOMINANT; MONOMAC
SYNDROME; SRSF2 MUTATIONS; PROSTATE-CANCER; POOR-PROGNOSIS;
GENE-MUTATIONS
AB Inherited or sporadic heterozygous mutations in the transcription factor GATA2 lead to a clinical syndrome characterized by non-tuberculous mycobacterial and other opportunistic infections, a severe deficiency in monocytes, B cells and natural killer cells, and progression from a hypocellular myelodysplastic syndrome to myeloid leukemias. To identify acquired somatic mutations associated with myeloid transformation in patients with GATA2 mutations, we sequenced the region of the ASXL1 gene previously associated with transformation from myelodysplasia to myeloid leukemia. Somatic, heterozygous ASXL1 mutations were identified in 14/48 (29%) of patients with GATA2 deficiency, including four out of five patients who developed a proliferative chronic myelomonocytic leukemia. Although patients with GATA2 mutations had a similarly high incidence of myeloid transformation when compared to previously described patients with ASXL1 mutations, GATA2 deficiency patients with acquired ASXL1 mutation were considerably younger, almost exclusively female, and had a high incidence of transformation to a proliferative chronic myelomonocytic leukemia. These patients may benefit from allogeneic hematopoietic stem cell transplantation before the development of acute myeloid leukemia or chronic myelomonocytic leukemia.
C1 [West, Robert R.; Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hsu, Amy P.; Holland, Steven M.; Cuellar-Rodriguez, Jennifer] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP West, RR (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM westrob@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, National
Institute of Allergy and Infectious Diseases; Mark Hatfield Clinical
Research Center
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, National
Institute of Allergy and Infectious Diseases, and the Mark Hatfield
Clinical Research Center.
NR 43
TC 23
Z9 23
U1 0
U2 5
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD FEB
PY 2014
VL 99
IS 2
BP 276
EP 281
DI 10.3324/haematol.2013.090217
PG 6
WC Hematology
SC Hematology
GA AH6PU
UT WOS:000336253900019
PM 24077845
ER
PT J
AU Kristinsson, SY
Gridley, G
Hoover, RN
Check, D
Landgren, O
AF Kristinsson, Sigurdur Y.
Gridley, Gloria
Hoover, Robert N.
Check, David
Landgren, Ola
TI Long-term risks after splenectomy among 8,149 cancer-free American
veterans: a cohort study with up to 27 years follow-up
SO HAEMATOLOGICA
LA English
DT Article
ID POSTSPLENECTOMY INFECTION; ANTIBODY-RESPONSE; PREVENTION; MORTALITY;
SPLEEN; ADULTS; POLYSACCHARIDE; THROMBOSIS; CHILDHOOD; CLEARANCE
AB Although preservation of the spleen following abdominal trauma and spleen-preserving surgical procedures have become gold standards, about 22,000 splenectomies are still conducted annually in the USA. Infections, mostly by encapsulated organisms, are the most well-known complications following splenectomy. Recently, thrombosis and cancer have become recognized as potential adverse outcomes post-splenectomy. Among more than 4 million hospitalized USA veterans, we assessed incidence and mortality due to infections, thromboembolism, and cancer including 8,149 cancer-free veterans who underwent splenectomy with a follow-up of up to 27 years. Relative risk estimates and 95% confidence intervals were calculated using time-dependent Poisson regression methods for cohort data. Splenectomized patients had an increased risk of being hospitalized for pneumonia, meningitis, and septicemia (rate ratios = 1.9-3.4); deep venous thrombosis and pulmonary embolism (rate ratios = 2.2); certain solid tumors: buccal, esophagus, liver, colon, pancreas, lung, and prostate (rate ratios = 1.3-1.9); and hematologic malignancies: non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and any leukemia (rate ratios = 1.8-6.0). They also had an increased risk of death due to pneumonia and septicemia (rate ratios = 1.6-3.0); pulmonary embolism and coronary artery disease (rate ratios = 1.4-4.5); any cancer: liver, pancreas, and lung cancer, non-Hodgkin lymphoma, Hodgkin lymphoma, and any leukemia (rate ratios = 1.3-4.7). Many of the observed risks were increased more than 10 years after splenectomy. Our results underscore the importance of vaccination, surveillance, and thromboprophylaxis after splenectomy.
C1 [Kristinsson, Sigurdur Y.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Kristinsson, Sigurdur Y.] Landspitali Natl Univ Hosp, Dept Hematol, Reykjavik, Iceland.
[Gridley, Gloria; Hoover, Robert N.; Check, David; Landgren, Ola] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Landgren, Ola] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kristinsson, SY (reprint author), Univ Iceland, Fac Med, Reykjavik, Iceland.
EM sigyngvi@hi.is
RI Kristinsson, Sigurdur /M-2910-2015; Check, David/J-7184-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476; Check,
David/0000-0003-3887-0493
FU National Cancer Institute (NCI), National Institutes of Health (NIH),
Bethesda, Maryland, USA
FX This work was funded by the Intramural Research Program of the National
Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda,
Maryland, USA.
NR 47
TC 45
Z9 46
U1 0
U2 1
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD FEB
PY 2014
VL 99
IS 2
BP 392
EP 398
DI 10.3324/haematol.2013.092460
PG 7
WC Hematology
SC Hematology
GA AH6PU
UT WOS:000336253900035
PM 24056815
ER
EF