FN Thomson Reuters Web of Science™ VR 1.0 PT S AU Agard, D Cheng, YF Glaeser, RM Subramaniam, S AF Agard, David Cheng, Yifan Glaeser, Robert M. Subramaniam, Sriram BE Hawkes, PW TI Single-Particle Cryo-Electron Microscopy (Cryo-EM): Progress, Challenges, and Perspectives for Further Improvement SO ADVANCES IN IMAGING AND ELECTRON PHYSICS, VOL 185 SE Advances in Imaging and Electron Physics LA English DT Review; Book Chapter ID BEAM-INDUCED MOTION; ELECTRON CRYOMICROSCOPY; EWALD SPHERE; 20S PROTEASOME; RESOLUTION; MACROMOLECULES; IMAGES; ICE; RECONSTRUCTIONS; CLASSIFICATION C1 [Agard, David] Univ Calif San Francisco, HHMI, San Francisco, CA 94158 USA. [Agard, David; Cheng, Yifan] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA. [Glaeser, Robert M.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. [Subramaniam, Sriram] NCI, Lab Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Glaeser, RM (reprint author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. EM rmglaeser@lbl.gov NR 46 TC 10 Z9 10 U1 9 U2 40 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1076-5670 BN 978-0-12-800144-8 J9 ADV IMAG ELECT PHYS JI Adv. Imag. Electron Phys. PY 2014 VL 185 BP 113 EP 137 DI 10.1016/B978-0-12-800144-8.00002-1 PG 25 WC Physics, Applied SC Physics GA BB0ML UT WOS:000340439000002 ER PT J AU Bouvier, A Deleaval, F Doyley, MM Tacheau, A Finet, G Le Floc'h, S Cloutier, G Pettigrew, RI Ohayon, J AF Bouvier, Adeline Deleaval, Flavien Doyley, Marvin M. Tacheau, Antoine Finet, Gerard Le Floc'h, Simon Cloutier, Guy Pettigrew, Roderic I. Ohayon, Jacques TI A new finite element method for inverse problems in structural analysis: application to atherosclerotic plaque elasticity reconstruction SO COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING LA English DT Meeting Abstract CT 39th Congress of the Societe-de-Biomecanique CY AUG 27-29, 2014 CL Valenciennes, FRANCE SP Soc Biomecanique DE atherosclerosis; finite element method; elastography; inverse problem ID THICKNESS C1 [Bouvier, Adeline] Univ Savoie, CNRS, Lab LAMA, UMR 5127, Chambery, France. [Bouvier, Adeline; Deleaval, Flavien; Tacheau, Antoine; Ohayon, Jacques] CNRS, Lab TIMC IMAGUJF, UMR 5525, Grenoble, France. [Doyley, Marvin M.] Univ Rochester, Rochester, NY USA. [Finet, Gerard] Univ Lyon 1, Hosp Civils Lyon, INSERM, U886, F-69365 Lyon, France. [Le Floc'h, Simon] Univ Montpellier 2, Lab LMGC, CNRS, UMR 5508, Montpellier, France. [Cloutier, Guy] Univ Montreal, Lab LBUM, CRCHUM, Montreal, PQ, Canada. [Pettigrew, Roderic I.] NIBIB, NIH, Bethesda, MD USA. [Ohayon, Jacques] Univ Savoie, Polytech Annecy Chambery, Chambery, France. RP Ohayon, J (reprint author), CNRS, Lab TIMC IMAGUJF, UMR 5525, Grenoble, France. EM Jacques.Ohayon@univ-savoie.fr RI Ohayon, Jacques/M-6576-2014 NR 9 TC 1 Z9 1 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1025-5842 EI 1476-8259 J9 COMPUT METHOD BIOMEC JI Comput. Methods Biomech. Biomed. Eng. PY 2014 VL 17 SU 1 BP 16 EP 17 DI 10.1080/10255842.2014.931071 PG 2 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA AN1XG UT WOS:000340376700009 PM 25074142 ER PT J AU Simon, R AF Simon, Richard TI STRATIFICATION AND PARTIAL ASCERTAINMENT OF BIOMARKER VALUE IN BIOMARKER-DRIVEN CLINICAL TRIALS SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Ascertainment; Biomarker; Clinical trials; Stratification ID DESIGNS AB This article examines the role of stratification of treatment assignment with regard to biomarker value in clinical trials that accept biomarker-positive and -negative patients but have a primary objective of evaluating treatment effect separately for the marker-positive subset. It also examines the issue of incomplete ascertainment of biomarker value and how this affects inference about treatment effect for the biomarker-positive subset of patients. I find that stratifying the randomization for the biomarker ensures that all patients will have tissue collected but is not necessary for the validity of inference for the biomarker-positive subset if there is complete ascertainment. If there is not complete ascertainment of biomarker values, it is important to establish that ascertainment is independent of treatment assignment. Having a large proportion of cases with biomarker ascertainment is not necessary for establishing internal validity of the treatment evaluation in biomarker-positive patients; independence of ascertainment and treatment is the important factor. Having a large proportion of cases with biomarker ascertainment makes it more likely that biomarker-positive patients with ascertainment are representative of the biomarker-positive patients in the clinical trial (with and without ascertainment), but since the patients in the clinical trial are a convenience sample of the population of patients potentially eligible for the trial, requiring a large proportion of cases with ascertainment does not facilitate generalizability of conclusions. C1 NCI, Rockville, MD 20892 USA. RP Simon, R (reprint author), NCI, 9609 Med Ctr Dr, Rockville, MD 20892 USA. EM rsimon@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 15 TC 2 Z9 2 U1 2 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2014 VL 24 IS 5 SI SI BP 1011 EP 1021 DI 10.1080/10543406.2014.931411 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA AN2MF UT WOS:000340418700005 PM 24935478 ER PT J AU Szerman, N Montoya, ID AF Szerman, Nestor Montoya, Ivan D. TI SPECIAL SECTION OF PAPERS PRESENTED AT THE III INTERNATIONAL CONGRESS ON DUAL DISORDERS SO JOURNAL OF DUAL DIAGNOSIS LA English DT Editorial Material C1 [Szerman, Nestor] Spanish Soc Dual Pathol, Bethesda, MD USA. [Szerman, Nestor] Organizing Comm Int Congress Dual Pathol, Bethesda, MD USA. [Szerman, Nestor] WPA Sect Dual Disorders Pathol, Bethesda, MD USA. [Szerman, Nestor] World Psychiat Assoc Sect Dual Disorders Pathol, Bethesda, MD USA. [Montoya, Ivan D.] NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD 20892 USA. RP Montoya, ID (reprint author), NIDA, DPMC, NIH, 6001 Execut Blvd,Room 4131, Bethesda, MD 20892 USA. EM imontoya@mail.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1550-4263 EI 1550-4271 J9 J DUAL DIAGN JI J. Dual Diagn. PY 2014 VL 10 IS 3 BP 145 EP 147 DI 10.1080/15504263.2014.930266 PG 3 WC Psychology, Clinical; Substance Abuse; Psychiatry SC Psychology; Substance Abuse; Psychiatry GA AN2BS UT WOS:000340388900006 PM 25392288 ER PT J AU Pecoraro, A Mimiaga, MJ O'Cleirigh, C Safren, SA Blokhina, E Verbitskaya, E Krupitsky, E Dvoriak, S Woody, G AF Pecoraro, Anna Mimiaga, Matthew J. O'Cleirigh, Conall Safren, Steven A. Blokhina, Elena Verbitskaya, Elena Krupitsky, Evgeny Dvoriak, Sergii Woody, George TI Lost-to-care and engaged-in-care HIV patients in Leningrad Oblast, Russian Federation: barriers and facilitators to medical visit retention SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV; AIDS; retention; attrition; Russian Federation; positive psychology ID ANTIRETROVIRAL THERAPY; DRUG-USERS; ADHERENCE AB Sixty-nine percent of the 1.5 million Eastern Europeans and Central Asians with HIV live in the Russian Federation. Antiretroviral therapy (ART) is effective but cannot help those who leave treatment. Focus groups with patients who dropped out of ART for >= 12 months (lost-to-care, LTCs, n = 21) or continued for >= 12 months (engaged-in-care; EICs; n = 24) were conducted in St. Petersburg. Structural barriers included stigma/discrimination and problems with providers and accessing treatment. Individual barriers included employment and caring for dependents, inaccurate beliefs about ART (LTC only), side-effects, substance use (LTCs, present; EICs, past), and depression. Desire to live, social support, and spirituality were facilitators for both; EICs also identified positive thinking and experiences with ART and healthcare/professionals. Interventions to facilitate retention and adherence are discussed. C1 [Pecoraro, Anna; Woody, George] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Pecoraro, Anna; Woody, George] NIDA Clin Trials Network, Delaware Valley Node, Philadelphia, PA USA. [Mimiaga, Matthew J.; O'Cleirigh, Conall; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Blokhina, Elena; Verbitskaya, Elena; Krupitsky, Evgeny] Pavlov State Med Univ, St Petersburg, Russia. [Dvoriak, Sergii] Ukrainian Inst Publ Hlth Policy, Kiev, Ukraine. RP Pecoraro, A (reprint author), Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. EM annp@mail.med.upenn.edu RI Verbitskaya, Elena/N-3867-2015 OI Verbitskaya, Elena/0000-0003-3770-993X FU NIDA NIH HHS [R01 DA026336, U10 DA013043]; PEPFAR NR 23 TC 2 Z9 2 U1 2 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2014 VL 26 IS 10 BP 1249 EP 1257 DI 10.1080/09540121.2014.897910 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA AM8NJ UT WOS:000340132300007 PM 24666174 ER PT B AU Lane, J Largent, M Rosen, R AF Lane, Julia Largent, Mark Rosen, Rebecca BE Cronin, B Sugimoto, CR TI Science Metrics and Science Policy SO BEYOND BIBLIOMETRICS: HARNESSING MULTIDIMENSIONAL INDICATORS OF SCHOLARLY IMPACT LA English DT Article; Book Chapter ID MODELS C1 [Lane, Julia; Rosen, Rebecca] Amer Inst Res, Washington, DC 20007 USA. [Lane, Julia] Univ Strasbourg, CNRS, BETA, Strasbourg, France. [Lane, Julia] Natl Sci Fdn, Sci Sci & Innovat Policy Program, Arlington, VA 22230 USA. [Largent, Mark] Michigan State Univ, James Madison Coll, E Lansing, MI 48824 USA. [Rosen, Rebecca] Natl Sci Fdn, AAAS Sci Policy, Arlington, VA 22230 USA. [Rosen, Rebecca] NIH, Bethesda, MD USA. RP Lane, J (reprint author), Amer Inst Res, Washington, DC 20007 USA. EM jlane@air.org; Largent@msu.edu; rrosen@air.org NR 29 TC 0 Z9 0 U1 0 U2 3 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-52551-0; 978-0-262-02679-6 PY 2014 BP 397 EP 411 PG 15 WC Information Science & Library Science SC Information Science & Library Science GA BA9ET UT WOS:000339323300022 ER PT J AU Mills, KL Goddings, AL Clasen, LS Giedd, JN Blakemore, SJ AF Mills, Kathryn L. Goddings, Anne-Lise Clasen, Liv S. Giedd, Jay N. Blakemore, Sarah-Jayne TI The Developmental Mismatch in Structural Brain Maturation during Adolescence SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Adolescence; Development; Gray matter; Dual systems; Magnetic resonance imaging; Risk taking ID HUMAN CEREBRAL-CORTEX; RISK-TAKING BEHAVIOR; REWARD; ADULTS; SEGMENTATION; TRAJECTORIES; ACTIVATION; CHILDHOOD; ACCUMBENS; RESPONSES AB Regions of the human brain develop at different rates across the first two decades of life, with some maturing before others. It has been hypothesized that a mismatch in the timing of maturation between subcortical regions (involved in affect and reward processing) and prefrontal regions (involved in cognitive control) underlies the increase in risk-taking and sensation-seeking behaviors observed during adolescence. Most support for this 'dual systems' hypothesis relies on cross-sectional data, and it is not known whether this pattern is present at an individual level. The current study utilizes longitudinal structural magnetic resonance imaging (MRI) data to describe the developmental trajectories of regions associated with risk-taking and sensation-seeking behaviors, namely, the amygdala, nucleus accumbens (NAcc) and prefrontal cortex (PFC). Structural trajectories of gray matter volumes were analyzed using FreeSurfer in 33 participants aged 7-30 years, each of whom had at least three high-quality MRI scans spanning three developmental periods: late childhood, adolescence and early adulthood (total 152 scans). The majority of individuals in our sample showed relatively earlier maturation in the amygdala and/or NAcc compared to the PFC, providing evidence for a mismatch in the timing of structural maturation between these structures. We then related individual developmental trajectories to retrospectively assessed self-reported risk-taking and sensation-seeking behaviors during adolescence in a subsample of 24 participants. Analysis of this smaller sample failed to find a relationship between the presence of a mismatch in brain maturation and risk-taking and sensation-seeking behaviors during adolescence. Taken together, it appears that the developmental mismatch in structural brain maturation is present in neurotypically developing individuals. This pattern of development did not directly relate to self-reported behaviors at an individual level in our sample, highlighting the need for prospective studies combining anatomical and behavioral measures. (C) 2014 S. Karger AG, Basel C1 [Mills, Kathryn L.; Goddings, Anne-Lise; Blakemore, Sarah-Jayne] UCL, Inst Cognit Neurosci, London, England. [Goddings, Anne-Lise] UCL, Inst Child Hlth, London, England. [Mills, Kathryn L.; Clasen, Liv S.; Giedd, Jay N.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Mills, KL (reprint author), UCL Inst Cognit Neurosci, 17 Queen Sq, London WC1N 3AR, England. EM kathryn.l.mills@gmail.com RI Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-2002-8978 FU NIH; NIH Intramural Research; NIH Graduate Partnership Program; Royal Society University Research Fellowship; MRC Clinical Training Research Fellowship FX This study was supported by the NIH, NIH Intramural Research and the NIH Graduate Partnership Program. S.-J.B. is funded by a Royal Society University Research Fellowship. A.-L.G. is funded by an MRC Clinical Training Research Fellowship. NR 51 TC 44 Z9 44 U1 6 U2 28 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 EI 1421-9859 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2014 VL 36 IS 3-4 BP 147 EP 160 DI 10.1159/000362328 PG 14 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA AM7BR UT WOS:000340020200001 PM 24993606 ER PT J AU Dincheva, I Pattwell, SS Tessarollo, L Bath, KG Lee, FS AF Dincheva, Iva Pattwell, Siobhan S. Tessarollo, Lino Bath, Kevin G. Lee, Francis S. TI BDNF Modulates Contextual Fear Learning during Adolescence SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Polymorphism; Development; Long-term memory; Brain-derived neurotrophic factor; TrkB.T1; Fear conditioning ID ACTIVITY-DEPENDENT SECRETION; TRUNCATED TRKB RECEPTORS; NEUROTROPHIC FACTOR; HIPPOCAMPAL FUNCTION; TYROSINE KINASE; CANDIDATE GENES; HUMAN-MEMORY; FULL-LENGTH; IN-VIVO; POLYMORPHISM AB Brain-derived neurotrophic factor (BDNF) is a growth factor that plays key roles in regulating higher-order emotional and cognitive processes including fear learning and memory. A common single-nucleotide polymorphism (SNP) has been identified in the human BDNF gene (BDNF Val66Met) that leads to decreased BDNF secretion and impairments in specific forms of fear learning in adult humans and genetically modified mice containing this SNP. As the emergence of anxiety and other fear-related disorders peaks during adolescence, we sought to better understand the impact of this BDNF SNP on fear learning during the transition through adolescence in BDNF Val66Met knock-in mice. Previously, we have shown that contextual fear expression is temporarily suppressed in wild-type mice during a distinct period in adolescence, but re-emerges at later, postadolescent ages. Until recently, it was unclear whether BDNF-TrkB signaling is involved in the modulation of hippocampal-dependent contextual fear learning and memory during this adolescent period. Here we show that in BDNF Val66Met mice, the presence of the Met allele does not alter contextual fear expression during adolescence, but when previously conditioned BDNFMet/Met mice are tested in adulthood, they fail to display the delayed expression of contextual fear compared to wild-type BDNFVal/Val controls, indicating that the Met allele may permanently alter hippocampal function, leading to persistent functioning that is indistinguishable from the adolescent state. Conversely, truncated TrkB receptor (TrkB.T1)-deficient (TrkB.T1(-/-)) mice, a genetic mouse model with increased BDNF-TrkB signaling through full-length TrkB receptors, exhibit an accelerated expression of contextual fear during adolescence compared to wild-type controls. Our results point to a critical function for BDNF-TrkB signaling in fear regulation in vivo, particularly during a potentially sensitive period in adolescence. (C) 2014 S. Karger AG, Basel C1 [Dincheva, Iva; Lee, Francis S.] Cornell Univ, Weill Cornell Med Coll, Dept Psychiat, New York, NY 10021 USA. [Dincheva, Iva; Lee, Francis S.] Cornell Univ, Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10021 USA. [Pattwell, Siobhan S.] Fred Hutchinson Canc Res Ctr, Dept Human Biol, Seattle, WA 98104 USA. [Tessarollo, Lino] NCI, Neural Dev Grp, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. [Bath, Kevin G.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. RP Bath, KG (reprint author), Brown Univ, Dept Neurosci, Box GL N,185 Meeting St, Providence, RI 02912 USA. EM kevin_bath@brown.edu; fslee@med.cornell.edu FU Sadder Institute; DeWitt-Wallace Fund of the New York Community Trust; Pritzker Consortium; Youth Anxiety Center; National Institutes of Health [HD055177, MH079513, NS052819] FX This work was supported by the Sadder Institute (B.J.C.), the DeWitt-Wallace Fund of the New York Community Trust (F.S.L.), the Pritzker Consortium (F.S.L.), the Youth Anxiety Center (F.S.L.) and National Institutes of Health grants HD055177 (to B.J.C. and S.S.P.), MH079513 (to B.J.C. and F.S.L.) and NS052819 (to F.S.L.). NR 34 TC 6 Z9 7 U1 1 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 EI 1421-9859 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2014 VL 36 IS 3-4 BP 269 EP 276 DI 10.1159/000358824 PG 8 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA AM7BR UT WOS:000340020200011 PM 24992985 ER PT J AU Buckingham-Howes, S Bento, SP Scaletti, LA Koenig, JI Granger, DA Black, MM AF Buckingham-Howes, Stacy Bento, Samantha P. Scaletti, Laura A. Koenig, James I. Granger, Douglas A. Black, Maureen M. TI Prenatal Drug Exposure Moderates the Association between Stress Reactivity and Cognitive Function in Adolescence SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Hypothalamic-Pituitary-Adrenal axis; Cortisol; Psychobiology ID COCAINE EXPOSURE; EARLY-CHILDHOOD; CORTISOL REACTIVITY; HIPPOCAMPAL VOLUME; HOME INTERVENTION; MEMORY ABILITY; TOXIC STRESS; LIFE-SPAN; CHILDREN; ADVERSITY AB Prenatal drug exposure (PDE) can undermine subsequent health and development. In a prospective longitudinal study we examine whether PDE moderates the link between stress reactivity and cognitive functioning in adolescence. Participants were 76 prenatally drug-exposed and 61 nonexposed (NE) community comparison African American youth (50% male, mean age 14.17 years) living in an urban setting. All participants completed neuropsychological and academic achievement tests (Children's Memory Scales, the California Verbal Learning Test-Children's version and the Wide Range Achievement Test 4) over the course of 1 day in a laboratory setting. Two mild stressors (Balloon Analog Risk Task-Youth and Behavioral Indicator of Resilience to Distress) were administered, with saliva samples (assayed for cortisol) collected pre- and poststress task. A higher percentage in the NE group, compared to the PDE group (26% vs. 12%, X-2 = 4.70, d.f. = 1, n = 137, p = 0.03), exhibited task-related increases in salivary cortisol. PDE moderated the association between stress reactivity and 11 of 15 cognitive performance scales. In each case, the NE stress reactive group had better cognitive performance than either the NE lower cortisol reactive group or the PDE group regardless of stress reactivity status. Stress-related reactivity and regulation of the hypothalamic-pituitary-adrenal axis in adolescence may be disrupted by PDE, and the disruption may be linked to lower cognitive performance. (C) 2014 S. Karger AG, Basel C1 [Buckingham-Howes, Stacy; Bento, Samantha P.; Black, Maureen M.] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. [Scaletti, Laura A.] Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA. [Granger, Douglas A.] Johns Hopkins Univ, Sch Nursing, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Koenig, James I.] NINDS, Rockville, MD USA. [Buckingham-Howes, Stacy; Granger, Douglas A.] Arizona State Univ, Inst Interdisciplinary Salivary Biosci Res, Tempe, AZ USA. RP Black, MM (reprint author), Univ Maryland, Sch Med, Dept Pediat, 737 West Lombard St,Suite 161, Baltimore, MD 21201 USA. EM mblack@peds.umaryland.edu FU National Institute on Drug Abuse [R01-DA07432, R01-DA021059, 1F32DA036274-01] FX This study was supported by the National Institute on Drug Abuse (R01-DA07432, R01-DA021059 and 1F32DA036274-01). NR 50 TC 2 Z9 2 U1 1 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 EI 1421-9859 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2014 VL 36 IS 3-4 BP 329 EP 337 DI 10.1159/000360851 PG 9 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA AM7BR UT WOS:000340020200017 PM 24819393 ER PT J AU Keller, H AF Keller, Heidi BE Otto, H Keller, H TI Introduction: understanding relationships - what we would need to know to conceptualize attachment as the cultural solution of a universal developmental task SO DIFFERENT FACES OF ATTACHMENT: CULTURAL VARIATIONS ON A UNIVERSAL HUMAN NEED LA English DT Editorial Material; Book Chapter ID ONE-YEAR-OLDS; STRANGE SITUATION; EVOLUTIONARY-THEORY; INFANT ATTACHMENT; Q-SORT; METAANALYSIS; SECURITY; BEHAVIOR; CHILD; REPRESENTATIONS C1 [Keller, Heidi] Univ Osnabruck, D-49069 Osnabruck, Germany. [Keller, Heidi] Lower Saxony Inst Early Childhood Educ & Dev, Res Unit Culture Learning & Dev, Osnabruck, Germany. RP Keller, H (reprint author), NICHD, Washington, DC USA. NR 76 TC 2 Z9 2 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-02774-9 PY 2014 BP 1 EP 24 D2 10.1017/CBO9781139226684 PG 24 WC Psychology, Developmental SC Psychology GA BA9UF UT WOS:000339874800002 ER PT J AU Carlson, VJ Harwood, RL AF Carlson, Vivian J. Harwood, Robin L. BE Otto, H Keller, H TI The precursors of attachment security: behavioral systems and culture SO DIFFERENT FACES OF ATTACHMENT: CULTURAL VARIATIONS ON A UNIVERSAL HUMAN NEED LA English DT Article; Book Chapter ID PUERTO-RICAN MOTHERS; SOCIALIZATION GOALS; HEALTH DEVELOPMENT; INFANT ATTACHMENT; UNITED-STATES; CHILD; ORGANIZATION; ANTECEDENTS; SENSITIVITY; DEPRESSION C1 [Carlson, Vivian J.] Univ St Joseph, Sch Grad & Profess Studies, Hartford, CT 06117 USA. [Harwood, Robin L.] MCHB, Rockville, MD USA. [Harwood, Robin L.] Univ Connecticut, Sch Family Studies, Storrs, CT USA. [Harwood, Robin L.] NICHD, NICHHD, Bethesda, MD USA. RP Carlson, VJ (reprint author), Univ St Joseph, Sch Grad & Profess Studies, Hartford, CT 06117 USA. NR 81 TC 1 Z9 1 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-02774-9 PY 2014 BP 278 EP 303 D2 10.1017/CBO9781139226684 PG 26 WC Psychology, Developmental SC Psychology GA BA9UF UT WOS:000339874800013 ER PT J AU Keller, H Otto, H AF Keller, Heidi Otto, Hiltrud BE Otto, H Keller, H TI Epilogue: the future of attachment SO DIFFERENT FACES OF ATTACHMENT: CULTURAL VARIATIONS ON A UNIVERSAL HUMAN NEED LA English DT Editorial Material; Book Chapter C1 [Keller, Heidi] Univ Osnabruck, D-49069 Osnabruck, Germany. [Keller, Heidi] Lower Saxony Inst Early Childhood Educ & Dev, Res Unit Culture Learning & Dev, Osnabruck, Germany. [Keller, Heidi] Int Assoc Cross Cultural Psychol, Reims, France. Univ Osnabruck, Dept Culture & Dev, D-49069 Osnabruck, Germany. RP Keller, H (reprint author), NICHD, Washington, DC 20060 USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-02774-9 PY 2014 BP 307 EP 312 D2 10.1017/CBO9781139226684 PG 6 WC Psychology, Developmental SC Psychology GA BA9UF UT WOS:000339874800014 ER PT S AU Goldman, D AF Goldman, David BE Stoltenberg, SF TI Genomics of Impulsivity: Integrating Genes and Neuroscience SO GENES AND THE MOTIVATION TO USE SUBSTANCES SE Nebraska Symposium on Motivation LA English DT Article; Proceedings Paper CT 61st Nebraska Symposium on Motivation CY APR 25-26, 2013 CL Lincoln, NE SP Univ Nebraska Lincoln, Dept Psychol ID REACTION-TIME-TASK; ANTISOCIAL-BEHAVIOR; MONOAMINE-OXIDASE; GENOTYPE; STRESS; POLYMORPHISMS; ADDICTIONS; DISORDER; FKBP5; RISK C1 [Goldman, David] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. EM davidgoldman@mail.nih.gov NR 29 TC 0 Z9 0 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0146-7875 BN 978-1-4939-0653-6; 978-1-4939-0652-9 J9 NEBR SYM MOTIV JI Nebr. Symp. Motiv. PY 2014 VL 61 BP 129 EP 139 DI 10.1007/978-1-4939-0653-6_7 PG 11 WC Psychology, Biological; Substance Abuse; Genetics & Heredity SC Psychology; Substance Abuse; Genetics & Heredity GA BB0JY UT WOS:000340269800007 PM 25306782 ER PT B AU Tani, J Maniadakis, M Paine, RW AF Tani, Jun Maniadakis, Michail Paine, Rainer W. BE Vargas, PA DiPaolo, EA Harvey, I Husbands, P TI Understanding Higher-Order Cognitive Brain Mechanisms by Conducting Evolutional Neuro-robotics Experiments SO HORIZONS OF EVOLUTIONARY ROBOTICS SE Intelligent Robots and Autonomous Agents LA English DT Article; Book Chapter ID DYNAMICAL-SYSTEMS; PREFRONTAL CORTEX; MODEL; FLEXIBILITY; NETWORK; RULES; TASKS C1 [Tani, Jun] RIKEN, Brain Sci Inst, Wako, Saitama, Japan. [Maniadakis, Michail] FORTH, Computat Vis & Robot Lab, Iraklion, Greece. [Paine, Rainer W.] NINDS, NIH, Bethesda, MD 20892 USA. RP Tani, J (reprint author), RIKEN, Brain Sci Inst, Wako, Saitama, Japan. NR 32 TC 0 Z9 0 U1 0 U2 2 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-32223-2; 978-0-262-02676-5 J9 INTEL ROBOT AUTON AG PY 2014 BP 219 EP 236 PG 18 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Robotics SC Computer Science; Engineering; Robotics GA BA5BP UT WOS:000336504100011 ER PT S AU Cai, H Maudsley, S Martin, B AF Cai, Huan Maudsley, Stuart Martin, Bronwen BE Delhanty, PJD VanDerLely, AJ TI What Is the Role of Metabolic Hormones in Taste Buds of the Tongue SO HOW GUT AND BRAIN CONTROL METABOLISM SE Frontiers of Hormone Research LA English DT Review; Book Chapter ID GLUCAGON-LIKE PEPTIDE-1; VASOACTIVE-INTESTINAL-PEPTIDE; DIABETIC DB/DB MOUSE; INDUCED OBESE RATS; SWEET TASTE; RECEPTOR-CELLS; CIRCUMVALLATE PAPILLAE; COEXPRESSION PATTERNS; NEUROPEPTIDE-Y; EXPRESSION AB Gustation is one of the important chemical senses that guides the organism to identify nutrition while avoiding toxic chemicals. An increasing number of metabolic hormones and/or hormone receptors have been identified in the taste buds of the tongue and are involved in modulating taste perception. The gustatory system constitutes an additional endocrine regulatory locus that affects food intake, and in turn whole-body energy homeostasis. Here we provide an overview of the main metabolic hormones known to be present in the taste buds of the tongue; discuss their potential functional roles in taste perception and energy homeostasis and how their functional integrity is altered in the metabolic imbalance status (obesity and diabetes) and aging process. Better understanding of the functional roles of metabolic hormones in flavor perception as well as the link between taste perception and peripheral metabolism may be vital for developing strategies to promote healthier eating and prevent obesity or lifestyle-related disorders. (C) 2014 S. Karger AG, Basel C1 [Cai, Huan; Maudsley, Stuart; Martin, Bronwen] NIA, Metab Unit, Lab Clin Invest, NIH, Baltimore, MD 21224 USA. RP Martin, B (reprint author), NIA, Metab Unit, Lab Clin Invest, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM martinbro@mail.nih.gov RI Cai, Huan/B-6578-2016 OI Cai, Huan/0000-0001-7731-8891 FU Intramural NIH HHS NR 59 TC 4 Z9 4 U1 3 U2 13 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-3073 BN 978-3-318-02639-9; 978-3-318-02638-2 J9 FRONT HORM RES JI Front.Horm.Res. PY 2014 VL 42 BP 134 EP 146 DI 10.1159/000358322 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BB0DB UT WOS:000340105100012 PM 24732931 ER PT J AU Lu, T Porter, AR Kennedy, AD Kobayashi, SD DeLeo, FR AF Lu, Thea Porter, Adeline R. Kennedy, Adam D. Kobayashi, Scott D. DeLeo, Frank R. TI Phagocytosis and Killing of Staphylococcus aureus by Human Neutrophils SO JOURNAL OF INNATE IMMUNITY LA English DT Article DE Neutrophils; Phagocytosis; Staphylococcus aureus ID HUMAN POLYMORPHONUCLEAR; GENOME SEQUENCE; VIRULENCE; INFECTIONS; COMPLEMENT; LEUKOCYTES; EVOLUTION; STRAINS; SERUM; MICROORGANISMS AB Neutrophils are essential for host defense against Staphylococcus aureus infections. Although significant progress has been made, our understanding of neutrophil interactions with S. aureus remains incomplete. To provide a more comprehensive view of this process, we investigated phagocytosis and killing of S. aureus by human neutrophils using varied assay conditions in vitro. A greater percentage of bacteria were internalized by adherent neutrophils compared to those in suspension, and, unexpectedly, uptake of S. aureus by adherent neutrophils occurred efficiently in the absence of opsonins. An antibody specific for S. aureus promoted uptake of unopsonized bacteria in suspension, but had little or no capacity to enhance phagocytosis of S. aureus opsonized with normal human serum or by adherent neutrophils. Collectively, these results indicate that assay conditions can have a significant influence on the phagocytosis and killing of S. aureus by neutrophils. More importantly, the results suggest a vaccine approach directed to enhance opsono-phagocytosis alone is not sufficient to promote increased killing of S. aureus by human neutrophils. With the emergence and reemergence of antibiotic-resistant microorganisms, establishing parameters that are optimal for studying neutrophil-S. aureus interactions will pave the way towards developing immune-directed strategies for anti-staphylococcal therapies. (C) 2014 S. Karger AG, Basel C1 [Lu, Thea; Porter, Adeline R.; Kennedy, Adam D.; Kobayashi, Scott D.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP DeLeo, FR (reprint author), NIAID, Rocky Mt Labs, NIH, 903 South 4th St, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank Brett Freedman and Ashley Schrammeck for assistance with phagocytosis and bactericidal activity assays. This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 48 TC 17 Z9 18 U1 2 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X EI 1662-8128 J9 J INNATE IMMUN JI J. Innate Immun. PY 2014 VL 6 IS 5 BP 639 EP 649 DI 10.1159/000360478 PG 11 WC Immunology SC Immunology GA AN1LS UT WOS:000340345900009 PM 24713863 ER PT J AU Chan, CC Goldstein, DA Davis, JL Sen, HN AF Chan, Chi-Chao Goldstein, Debra A. Davis, Janet L. Sen, H. Nida TI Gender and Uveitis SO JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID AUTOIMMUNITY C1 [Chan, Chi-Chao; Sen, H. Nida] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Goldstein, Debra A.] Northwest Feinberg Sch Med, Dept Ophthalmol, Chicago, IL USA. [Davis, Janet L.] Univ Miami, Sch Med, Bascom Palmer Eye Inst, Miami, FL USA. RP Chan, CC (reprint author), NEI, Immunol Lab, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov NR 5 TC 1 Z9 1 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-004X EI 2090-0058 J9 J OPHTHALMOL JI J. Ophthalmol. PY 2014 AR 818070 DI 10.1155/2014/818070 PG 2 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA AN0KF UT WOS:000340272800001 ER PT J AU Kodavanti, UP Andrews, D Schladweiler, MC Gavett, SH Dodd, DE Cyphert, JM AF Kodavanti, Urmila P. Andrews, Debora Schladweiler, Mette C. Gavett, Stephen H. Dodd, Darol E. Cyphert, Jaime M. TI EARLY AND DELAYED EFFECTS OF NATURALLY OCCURRING ASBESTOS ON SERUM BIOMARKERS OF INFLAMMATION AND METABOLISM SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID PARTICULATE AIR-POLLUTION; ACUTE-PHASE RESPONSE; LIBBY AMPHIBOLE; MALIGNANT MESOTHELIOMA; PLEURAL MESOTHELIOMA; INHALATION EXPOSURE; FISCHER-344 RATS; GENE-EXPRESSION; LUNG FIBROSIS; OSTEOPONTIN AB Studies recently showed that intratracheal (IT) instillation of Libby amphibole (LA) increases circulating acute-phase proteins (APP; alpha-2 macroglobulin, A2M; and alpha-1 acid glycoprotein, AGP) and inflammatory biomarkers (osteopontin and lipocalin) in rats. In this study, objectives were to (1) compare changes in biomarkers of rats after instillation of different naturally occurring asbestos (NOA) minerals including LA, Sumas Mountain chrysotile (SM), El Dorado Hills tremolite (ED), and Ontario ferroactinolite cleavage fragments (ON), and (2) examine biomarkers after subchronic LA or amosite inhalation exposure. Rat-respirable fractions (aerodynamic diameter approximately 2.5 mu m) prepared by water elutriation were delivered via a single IT instillation at doses of 0, 0.5, and 1.5 mg/rat in male F344 rats. Nose-only inhalation exposures were performed at 0, 1, 3.3, and 10 mg/m(3) for LA and at 3.3 mg /m(3) for amosite, 6h/d, 5 d/wk for 13 wk. Inflammation, metabolic syndrome, and cancer biomarkers were analyzed in the serum for up to 18 mo. IT instillation of some asbestos materials significantly increased serum AGP and A2M but to a varying degree (SM = LA > ON = ED). Numerical increases in interleukin (IL)-6 and osteopontin occurred in rats instilled with SM. SM and ED also elevated leptin and insulin at 15 mo, suggesting potential metabolic effects. LA inhalation tended to raise A2M at d 1 but not cytokines. Serum mesothelin appeared to elevate after 18 mo of LA inhalation. These results suggest that the lung injury induced by high levels of asbestos materials may be associated with systemic inflammatory changes and predisposition to insulin resistance. C1 [Kodavanti, Urmila P.; Schladweiler, Mette C.; Gavett, Stephen H.] US EPA, Cardiopulm & Immunotoxicol Branch, Environm Publ Hlth Div, Natl Hlth & Environm Effects Res Lab,Off Res & De, Res Triangle Pk, NC 27711 USA. [Andrews, Debora] US EPA, Prote Core, Res Cores Unit, Natl Hlth & Environm Effects Res Lab,Off Res & De, Res Triangle Pk, NC 27711 USA. [Dodd, Darol E.] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA. [Cyphert, Jaime M.] NIEHS, Matrix Biol Grp, Lab Resp Biol, Div Intramural Res,NIH, Res Triangle Pk, NC 27709 USA. RP Kodavanti, UP (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, B143-01, Res Triangle Pk, NC 27711 USA. EM Kodavanti.Urmila@epa.gov NR 45 TC 8 Z9 8 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1528-7394 EI 1087-2620 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2014 VL 77 IS 17 BP 1024 EP 1039 DI 10.1080/15287394.2014.899171 PG 16 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AN0MW UT WOS:000340279700003 PM 25072823 ER PT J AU Chernoff, N Rogers, EH Zehr, RD Gage, MI Travlos, GS Malarkey, DE Brix, A Schmid, JE Hill, D AF Chernoff, N. Rogers, E. H. Zehr, R. D. Gage, M. I. Travlos, G. S. Malarkey, D. E. Brix, A. Schmid, J. E. Hill, D. TI THE COURSE OF TOXICITY IN THE PREGNANT MOUSE AFTER EXPOSURE TO THE CYANOBACTERIAL TOXIN CYLINDROSPERMOPSIN: CLINICAL EFFECTS, SERUM CHEMISTRIES, HEMATOLOGY, AND HISTOPATHOLOGY SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID ISLAND MYSTERY DISEASE; SWISS ALBINO MICE; 2 GERMAN LAKES; RACIBORSKII CYANOBACTERIA; 1ST REPORT; CYANOTOXIN CYLINDROSPERMOPSIN; ORAL TOXICITY; IDENTIFICATION; STRAIN; DEOXYCYLINDROSPERMOPSIN AB Cylindrospermopsin (CYN) is a toxin produced by a variety of fresh-water cyanobacterial species worldwide and induces significant adverse effects in both livestock and humans. This study investigated the course of CYN-induced toxicity in pregnant mice exposed daily during either the period of major organogenesis (gestation days [GD] 8-12) or fetal growth (GD13-17). Endpoints include clinical signs of toxicity, serum analyses to evaluate hepatic and renal function, histopathology of liver and kidney, and hematology. Study animals were administered 50 mu g/kg CYN once daily by ip route and euthanized 24 h after 1, 2, 3, 4, or 5 consecutive doses, or 6 or 13 d after the dosing period. The course of the CYN-induced effects was determined at all euthanasia times for the endpoints just outlined. Results indicated that CYN is a toxin, producing lethality in dams during the early part of gestation, significant weight loss, and bleeding in the gastrointestinal tract, tail tip, and peri-orbital tissues. Effects also included alterations in serum markers for liver function, histopathological changes in liver and kidney tissues, electrolyte abnormalities, leukocytosis, and posttreatment thrombocytopenia and reticulocytosis. The onset of symptoms was rapid, producing reductions in weight gain in GD8-12 animals, bleeding in the vaginal area in GD13-17 animals, and significant increases in sorbitol dehydrogenase (SDH) in both groups after a single dose. Although the GD8-12 dams displayed a 50% lethality, in GD13-17 animals only a single death occurred. Alterations seen in hepatic and renal function or histopathology do not appear to be of sufficient severity to produce death. Evidence indicates that bleeding may play a critical role in the onset of symptoms and eventually, in the observed lethality. C1 [Chernoff, N.; Rogers, E. H.; Zehr, R. D.; Gage, M. I.; Schmid, J. E.; Hill, D.] US EPA, ORD, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. [Travlos, G. S.; Malarkey, D. E.; Brix, A.] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. RP Chernoff, N (reprint author), US EPA, MD B105-04, Res Triangle Pk, NC 27711 USA. EM chernoff.neil@epa.gov FU Division of the National Toxicology Program of the NIH, National Institute of Environmental Health Sciences; U.S. Environmental Protection Agency FX This research was supported [in part] by the Division of the National Toxicology Program of the NIH, National Institute of Environmental Health Sciences. The information in this document has been funded by the U.S. Environmental Protection Agency. It has been subject to review by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. NR 56 TC 2 Z9 2 U1 0 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1528-7394 EI 1087-2620 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2014 VL 77 IS 17 BP 1040 EP 1060 DI 10.1080/15287394.2014.919838 PG 21 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AN0MW UT WOS:000340279700004 PM 25072824 ER PT B AU Ujhazy, P Hruszkewycz, AM Hecht, TT AF Ujhazy, Peter Hruszkewycz, Andrew M. Hecht, Toby T. BE Srivastava, R Maksymowicz, W Lopaczynski, W TI Sport Programs and Transcational Research in Cancer SO LOST IN TRANSLATION: BARRIERS TO INCENTIVES FOR TRANSLATIONAL RESEARCH IN MEDICAL SCIENCES LA English DT Article; Book Chapter ID CELL LUNG-CANCER; SPORADIC COLORECTAL ADENOMAS; DIFLUOROMETHYLORNITHINE PLUS SULINDAC; CAROLINA BREAST-CANCER; TUMOR-SUPPRESSOR GENE; DOUBLE-BLIND TRIAL; PROSTATE-CANCER; MULTIPLE-MYELOMA; HOMOZYGOUS DELETION; MOLECULAR PORTRAITS C1 [Ujhazy, Peter] NCI, Rockville, MD USA. [Hruszkewycz, Andrew M.; Hecht, Toby T.] NCI, Translat Res Program, Div Canc Treatment & Diag, Rockville, MD 20850 USA. RP Ujhazy, P (reprint author), NCI, Translat Res Program, Div Canc Treatment & Diag, 9609 Med Ctr Dr,Room 3W106 MSC 9726, Rockville, MD 20892 USA. EM ujhazyp@mail.nih.gov NR 69 TC 0 Z9 0 U1 0 U2 2 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-4489-07-2; 978-981-4489-06-5 PY 2014 BP 155 EP 179 D2 10.1142/8782 PG 25 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA BA8JY UT WOS:000338207800009 ER PT B AU Moody, TW Smith, JP AF Moody, Terry W. Smith, Jill P. BE Srivastava, R Maksymowicz, W Lopaczynski, W TI Translational Research of Tyrosine Kinase Inhibitors in Cancer SO LOST IN TRANSLATION: BARRIERS TO INCENTIVES FOR TRANSLATIONAL RESEARCH IN MEDICAL SCIENCES LA English DT Article; Book Chapter ID CELL LUNG-CANCER; GROWTH-FACTOR-RECEPTOR; GASTRIN-RELEASING-PEPTIDE; BOMBESIN-LIKE PEPTIDES; RANDOMIZED PHASE-II; EGFR MUTATIONS; ANTITUMOR-ACTIVITY; GENE-MUTATIONS; HUMAN-BREAST; NECK-CANCER C1 [Moody, Terry W.] NCI, Ctr Canc Res, Off Director, Bethesda, MD 20892 USA. [Smith, Jill P.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD USA. RP Moody, TW (reprint author), NCI, Off Director, CCR, Bldg 31,Rm 4A48, Bethesda, MD 20892 USA. EM moodyt@mail.nih.gov NR 81 TC 1 Z9 1 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-4489-07-2; 978-981-4489-06-5 PY 2014 BP 221 EP 245 D2 10.1142/8782 PG 25 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA BA8JY UT WOS:000338207800012 ER PT B AU Szabo, E AF Szabo, Eva BE Srivastava, R Maksymowicz, W Lopaczynski, W TI Developmental of Translational Sciences Based on Lung Cancer SO LOST IN TRANSLATION: BARRIERS TO INCENTIVES FOR TRANSLATIONAL RESEARCH IN MEDICAL SCIENCES LA English DT Article; Book Chapter ID PREVENTION CLINICAL-TRIALS; BREAST-CANCER; BETA-CAROTENE; CHEMOPREVENTION; MUTATIONS; ROFECOXIB; SUBTYPES; ST1571 C1 NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Szabo, E (reprint author), NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, NIH, 9609 Med Ctr Dr,Rm 5E-102,MSC 9781, Bethesda, MD 20892 USA. EM szaboe@mail.nih.gov NR 24 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-4489-07-2; 978-981-4489-06-5 PY 2014 BP 287 EP 297 D2 10.1142/8782 PG 11 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA BA8JY UT WOS:000338207800014 ER PT B AU Manak, M Ji, JP AF Manak, Mark Ji, Jiuping BE Srivastava, R Maksymowicz, W Lopaczynski, W TI Translational Research in Molecular Diagnostics of Infectious Disease SO LOST IN TRANSLATION: BARRIERS TO INCENTIVES FOR TRANSLATIONAL RESEARCH IN MEDICAL SCIENCES LA English DT Article; Book Chapter ID IMMUNODEFICIENCY-VIRUS TYPE-1; RESPIRATORY SYNCYTIAL VIRUS; HIV-1 DRUG-RESISTANCE; REVERSE-TRANSCRIPTASE; NEISSERIA-GONORRHOEAE; CHLAMYDIA-TRACHOMATIS; UNITED-STATES; VIRAL LOAD; INFLUENZA; CHILDREN C1 [Manak, Mark] Walter Reed Army Inst Res, Dept Diagnost & Monitoring, US Mil HIV Res Program MHRP, HJF, Silver Spring, MD USA. [Ji, Jiuping] Frederick Natl Lab Canc Res, Natl Clin Target Validat Lab, Frederick, MD 21702 USA. RP Ji, JP (reprint author), Frederick Natl Lab Canc Res, Natl Clin Target Validat Lab, Frederick, MD 21702 USA. EM jijiupi@mail.nih.gov NR 89 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-4489-07-2; 978-981-4489-06-5 PY 2014 BP 301 EP 339 D2 10.1142/8782 PG 39 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA BA8JY UT WOS:000338207800015 ER PT B AU Wideroff, L AF Wideroff, Louise BE Srivastava, R Maksymowicz, W Lopaczynski, W TI Health Services and Economics in Translational Science SO LOST IN TRANSLATION: BARRIERS TO INCENTIVES FOR TRANSLATIONAL RESEARCH IN MEDICAL SCIENCES LA English DT Article; Book Chapter ID COST-EFFECTIVENESS; BREAST-CANCER; CLINICAL EFFECTIVENESS; PERSONALIZED MEDICINE; QUALITY IMPROVEMENT; SYSTEMATIC REVIEWS; COLORECTAL-CANCER; GENOMIC MEDICINE; CARE; SURVEILLANCE C1 NIDA, Bethesda, MD 20892 USA. RP Wideroff, L (reprint author), NIDA, 6001 Execut Blvd,Rm 4271,MSC 9555, Bethesda, MD 20892 USA. EM wideroff@nih.gov NR 69 TC 0 Z9 0 U1 1 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-4489-07-2; 978-981-4489-06-5 PY 2014 BP 697 EP 715 D2 10.1142/8782 PG 19 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA BA8JY UT WOS:000338207800029 ER PT B AU Hoskins, J Jia, JP Amundadottir, LT AF Hoskins, Jason Jia, Jinping Amundadottir, Laufey T. BE Azmi, AS TI Genetic Susceptibility and Risk of Pancreatic Cancer SO MOLECULAR DIAGNOSTICS AND TREATMENT OF PANCREATIC CANCER: SYSTEMS AND NETWORK BIOLOGY APPROACHES LA English DT Article; Book Chapter ID GENOME-WIDE ASSOCIATION; COHORT-CONSORTIUM PANSCAN; ABO BLOOD-GROUP; INDUCED BLOCKING FACTOR; BODY-MASS INDEX; PROSTATE-CANCER; POOLED-ANALYSIS; PATHWAY ANALYSIS; LUNG-CANCER; HEREDITARY PANCREATITIS C1 [Hoskins, Jason; Jia, Jinping; Amundadottir, Laufey T.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Hoskins, J (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. OI Hoskins, Jason/0000-0001-6944-1996 NR 153 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS PI CLUJ-NAPOCA PA 3-5 MANASTUR STREET, CLUJ-NAPOCA, 400372, ROMANIA BN 978-0-12-407946-5; 978-0-12-408103-1 PY 2014 BP 169 EP 194 DI 10.1016/B978-0-12-408103-1.00008-X PG 26 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA BA7TM UT WOS:000337757400009 ER PT B AU Lee, CN He, T McCaffrey, I Birse, CE McKinnon, K Domon, B Ruben, SM Moore, PA AF Lee, Candy N. He, Tao McCaffrey, Ian Birse, Charles E. McKinnon, Katherine Domon, Bruno Ruben, Steven M. Moore, Paul A. BE Azmi, AS TI RNAi Validation of Pancreatic Cancer Antigens Identified by Cell Surface Proteomics SO MOLECULAR DIAGNOSTICS AND TREATMENT OF PANCREATIC CANCER: SYSTEMS AND NETWORK BIOLOGY APPROACHES LA English DT Article; Book Chapter ID DIFFERENTIALLY EXPRESSED PROTEINS; LASER-CAPTURE MICRODISSECTION; DUCTAL ADENOCARCINOMA; MEMBRANE-PROTEINS; MASS-SPECTROMETRY; GEL-ELECTROPHORESIS; TARGET DISCOVERY; FLOW-CYTOMETRY; SIRNA; INTERFERENCE C1 [Lee, Candy N.; He, Tao; McCaffrey, Ian; Birse, Charles E.; McKinnon, Katherine; Domon, Bruno; Ruben, Steven M.; Moore, Paul A.] Celera, Dept Prot Therapeut, Rockville, MD 20850 USA. [Lee, Candy N.] Pfizer, San Francisco, CA USA. [Birse, Charles E.] Celera, Alameda, CA USA. [He, Tao] Pfizer, Cambridge, MA USA. [Moore, Paul A.] MacroGenics Inc, Rockville, MD USA. [McCaffrey, Ian] Genentech Inc, San Francisco, CA 94080 USA. [McKinnon, Katherine] NCI, Bethesda, MD 20892 USA. [Domon, Bruno] CRP Sante, Luxembourg Clin Prote Ctr, Luxembourg, Luxembourg. RP Lee, CN (reprint author), Celera, Dept Prot Therapeut, Rockville, MD 20850 USA. NR 100 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS PI CLUJ-NAPOCA PA 3-5 MANASTUR STREET, CLUJ-NAPOCA, 400372, ROMANIA BN 978-0-12-407946-5; 978-0-12-408103-1 PY 2014 BP 245 EP 277 DI 10.1016/B978-0-12-408103-1.00011-X PG 33 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA BA7TM UT WOS:000337757400012 ER PT J AU Jayasekara, PS Jacobson, KA AF Jayasekara, P. Suresh Jacobson, Kenneth A. TI RAPID SYNTHESIS OF ALKOXYAMINE HYDROCHLORIDE DERIVATIVES FROM ALKYL BROMIDE AND N,N'-DI-TERT-BUTOXYCARBONYLHYDROXYLAMINE [(Boc)(2)NOH] SO SYNTHETIC COMMUNICATIONS LA English DT Article DE Alkoxyamine; alkyl bromide; O-alkylation AB The conventional route to alkoxyamine hydrochloride derivatives is by reaction of alkyl bromides with N-hydroxyphthalimide or N-hydroxysuccinimide followed by addition of hydrazine and HCl. Transformation of an alkyl bromide to the corresponding alkoxyamine hydrochloride can be accomplished more rapidly in good yields without using hazardous hydrazine by reaction of (Boc)(2)NOH (N,N'-di-tert-butoxycarbonylhydroxylamine) and alkyl bromide followed by addition of HCl. Alkoxyamine hydrochlorides are powerful reagents in organic synthesis that can be used to synthesize alkoxyimino derivatives after condensation with a ketone or aldehyde. C1 [Jayasekara, P. Suresh; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, NIH, LBC, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, NIH, LBC, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU NIDDK, National Institutes of Health FX Support from the Intramural Research Program of NIDDK, National Institutes of Health, is acknowledged. NR 11 TC 1 Z9 1 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0039-7911 EI 1532-2432 J9 SYNTHETIC COMMUN JI Synth. Commun. PY 2014 VL 44 IS 16 BP 2344 EP 2347 DI 10.1080/00397911.2014.895014 PG 4 WC Chemistry, Organic SC Chemistry GA AM8FZ UT WOS:000340109000004 PM 25368434 ER PT J AU Yavuz, S Apolo, AB Kummar, S del Rivero, J Madan, RA Shawker, T Reynolds, J Celi, FS AF Yavuz, Sahzene Apolo, Andrea B. Kummar, Shivaani del Rivero, Jaydira Madan, Ravi A. Shawker, Thomas Reynolds, James Celi, Francesco S. TI Cabozantinib-Induced Thyroid Dysfunction: A Review of Two Ongoing Trials for Metastatic Bladder Cancer and Sarcoma SO THYROID LA English DT Review ID RENAL-CELL CARCINOMA; TYROSINE KINASE INHIBITORS; SUNITINIB-INDUCED HYPOTHYROIDISM; JAPANESE PATIENTS; DESTRUCTIVE THYROIDITIS; INDUCED THYROTOXICOSIS; SORAFENIB; AXITINIB; ABNORMALITIES; SHRINKAGE AB Background: Thyroid dysfunction is a common adverse event associated with tyrosine kinase inhibitors (TKI), but its underlying pathophysiology is unclear. Cabozantinib is a novel TKI currently Food and Drug Administration approved for advanced medullary thyroid cancer and tested in clinical trials on solid tumors including prostate, liver, bladder, breast, and ovarian cancer. Methods: We analyzed the thyroid function of patients enrolled in two phase 2 clinical trials using cabozantinib at the National Institutes of Health Clinical Center. Two cases of thyroiditis associated with cabozantinib therapy are presented in detail, and a systematic review of the literature on TKI-associated thyroid dysfunction is also discussed. Results: Between September 2012 and September 2013, 33 patients were treated with cabozantinib, and follow-up thyroid function tests were available for 31 (20 males, 11 females; age 59 +/- 1 years). Thyroid dysfunction was recorded in the majority of patients (93.1%), with a predominance of subclinical hypothyroidism. Two cases showed a biphasic pattern of thyroid dysfunction characterized by a transient thyrotoxicosis followed by hypothyroidism. Color Doppler demonstrated an increase in vascularization during the thyrotoxic phase, but no uptake was visualized on nuclear medicine imaging. A systematic review of the literature resulted in the identification of 40 original manuscripts, of which 13 were case series and 6 were case reports describing TKI-associated thyroid dysfunction. Conclusion: TKI therapy often results in clinically significant thyroid dysfunction. Cabozantinib treatment commonly results in thyroid dysfunction varying from subclinical hypothyroidism to symptomatic thyrotoxicosis. Early detection and characterization of cabozantinib-associated thyroid dysfunction and close follow-up are essential to provide adequate management of this common adverse event. C1 [Yavuz, Sahzene; Celi, Francesco S.] NIDDK, Diabet Endocrine & Obes Branch, Bethesda, MD USA. [Apolo, Andrea B.; Kummar, Shivaani; Madan, Ravi A.] NCI, Bethesda, MD 20892 USA. [del Rivero, Jaydira] NICHD, Bethesda, MD USA. [Shawker, Thomas; Reynolds, James] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Celi, Francesco S.] Virginia Commonwealth Univ, Div Endocrinol & Metab, Richmond, VA USA. RP Celi, FS (reprint author), NIH, Div Endocrinol & Metab, 1101 East Marshall St,Sanger Hall,Room 7-007, Richmond, VA 23298 USA. EM fsceli@vcu.edu FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases program [Z01-DK047057-02]; National Cancer Institute; Clinical Center, National Institutes of Health FX We are grateful for the help of the National Institutes of Health Clinical Center staff including nurses, clinical and research fellows, and study participants. This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases program Z01-DK047057-02, National Cancer Institute, and the Clinical Center, National Institutes of Health. NR 39 TC 6 Z9 6 U1 0 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PY 2014 VL 24 IS 8 BP 1223 EP 1231 DI 10.1089/thy.2013.0621 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AM9JM UT WOS:000340197700004 PM 24724719 ER PT J AU Pirone, JR Smith, M Kleinstreuer, NC Burns, TA Strickland, J Dancik, Y Morris, R Rinckel, LA Casey, W Jaworska, JS AF Pirone, Jason R. Smith, Marjolein Kleinstreuer, Nicole C. Burns, Thomas A. Strickland, Judy Dancik, Yuri Morris, Richard Rinckel, Lori A. Casey, Warren Jaworska, Joanna S. TI Open Source Software Implementation of an Integrated Testing Strategy for Skin Sensitization Potency Based on a Bayesian Network SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Article DE skin sensitization; integrated testing strategy; allergic contact dermatitis; Bayesian network; R ID REPRODUCIBLE RESEARCH; PACKAGE AB An open source implementation of a previously published integrated testing strategy (ITS) for skin sensitization using a Bayesian network has been developed using R, a free and open source statistical computing language. The ITS model provides probabilistic predictions of skin sensitization potency based on in silico and in vitro information as well as skin penetration characteristics from a published bioavailability model (Kasting et al., 2008). The structure of the Bayesian network was designed to be consistent with the adverse outcome pathway published by the OECD (Jaworska et al., 2011, 2013). In this paper, the previously published data set (Jaworska et al., 2013) is improved by two data corrections and a modified application of the Kasting model. The new data set implemented in the original commercial software package and the new R version produced consistent results. The data and a fully documented version of the code are publicly available (http://ntp.niehs.nih.gov/go/its). C1 [Pirone, Jason R.; Smith, Marjolein; Morris, Richard] Social & Sci Syst Inc, Durham, NC USA. [Kleinstreuer, Nicole C.; Burns, Thomas A.; Strickland, Judy; Rinckel, Lori A.] Integrated Lab Syst Inc, Morrisville, NC USA. [Dancik, Yuri; Jaworska, Joanna S.] Procter & Gamble NV, Strombeek Bever, Belgium. [Casey, Warren] NIEHS, Natl Toxicol Program, Interagency Ctr Evaluat Alternat Toxicol Methods, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Casey, W (reprint author), NIEHS, NICEATM, POB 12233,Mail Stop K2-16, Res Triangle Pk, NC 27709 USA. EM warren.casey@nih.gov OI Dancik, Yuri/0000-0002-3652-9673; Kleinstreuer, Nicole/0000-0002-7914-3682 NR 18 TC 11 Z9 11 U1 0 U2 4 PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH PI HEILDEBERG PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY SN 1868-596X EI 1868-8551 J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2014 VL 31 IS 3 BP 336 EP 340 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AL9NU UT WOS:000339468800009 PM 24687303 ER PT J AU Andersen, ME Betts, K Dragan, Y Fitzpatrick, S Goodman, JL Hartung, T Himmelfarb, J Ingber, DE Jacobs, A Kavlock, R Kolaja, K Stevens, JL Tagle, D Taylor, DL Throckmorton, D AF Andersen, Melvin E. Betts, Kellyn Dragan, Yvonne Fitzpatrick, Suzanne Goodman, Jesse L. Hartung, Thomas Himmelfarb, Jonathan Ingber, Donald E. Jacobs, Abigail Kavlock, Robert Kolaja, Kyle Stevens, James L. Tagle, Dan Taylor, D. Lansing Throckmorton, Douglas TI Developing Microphysiological Systems for Use as Regulatory Tools - Challenges and Opportunities SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Editorial Material ID CHIP C1 [Andersen, Melvin E.] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA. [Dragan, Yvonne] AstraZeneca, Waltham, MA USA. [Fitzpatrick, Suzanne] US FDA, Ctr Food Safety & Appl Nutr, Silver Spring, MD USA. [Goodman, Jesse L.] US FDA, Silver Spring, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Ctr Alternat Anim Testing, Baltimore, MD USA. [Himmelfarb, Jonathan] Univ Washington, Kidney Res Inst, Seattle, WA USA. [Ingber, Donald E.] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA. [Jacobs, Abigail; Throckmorton, Douglas] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Kavlock, Robert] US EPA, Res Triangle Pk, NC USA. [Kolaja, Kyle] Cellular Dynamics Int Inc, Madison, WI USA. [Stevens, James L.] Lilly Res Labs, Greenfield, IN 46140 USA. [Tagle, Dan] Natl Ctr Adv Translat Sci, NIH, Bethesda, MD USA. [Taylor, D. Lansing] Univ Pittsburgh, Drug Discovery Inst, Pittsburgh, PA USA. RP Betts, K (reprint author), 8023 Glenside Dr, Takoma Pk, MD USA. EM k_betts@nasw.org OI Andersen, Melvin/0000-0002-3894-4811 FU NCATS NIH HHS [U18 TR000547, UH3 TR000504, UH2 TR000504] NR 6 TC 10 Z9 10 U1 2 U2 5 PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH PI HEILDEBERG PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY SN 1868-596X EI 1868-8551 J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2014 VL 31 IS 3 BP 364 EP 367 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AL9NU UT WOS:000339468800012 PM 25061900 ER PT S AU Bainbridge, KE Wallhagen, MI AF Bainbridge, Kathleen E. Wallhagen, Margaret I. BE Fielding, JE TI Hearing Loss in an Aging American Population: Extent, Impact, and Management SO ANNUAL REVIEW OF PUBLIC HEALTH, VOL 35 SE Annual Review of Public Health LA English DT Review; Book Chapter DE age-related hearing loss; health-related quality of life; hearing aids; screening ID QUALITY-OF-LIFE; NUTRITION EXAMINATION SURVEY; BLUE MOUNTAINS HEARING; OLDER-ADULTS; UNITED-STATES; NATIONAL-HEALTH; RISK-FACTORS; US ADULTS; AID USE; RANDOMIZED-TRIAL AB Despite contributing substantially to disability in the United States, age-related hearing loss is an underappreciated public health concern. Loss of hearing sensitivity has been documented in two-thirds of adults aged 70 years and older and has been associated with communication difficulties, lower health-related quality of life, and decreased physical and cognitive function. Management strategies for age-related hearing loss are costly, yet the indirect costs due to lost productivity among people with communication difficulties are also substantial and likely to grow. Hearing aids can improve health-related quality of life, but the majority of people with documented hearing loss do not report using them. Uncovering effective means to improve the utilization of hearing health care services is essential for meeting the hearing health care demands of our aging population. The importance of hearing for general well-being warrants an effort to enhance awareness among the general population of the indications of hearing loss and options for assistance. C1 [Bainbridge, Kathleen E.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. [Wallhagen, Margaret I.] Univ Calif San Francisco, Sch Nursing, Dept Physiol Nursing, San Francisco, CA 94143 USA. RP Bainbridge, KE (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. EM bainbridgek@mail.nih.gov; meg.wallhagen@nursing.ucsf.edu NR 67 TC 16 Z9 18 U1 3 U2 17 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0163-7525 BN 978-0-8243-2735-4 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2014 VL 35 BP 139 EP 152 DI 10.1146/annurev-publhealth-032013-182510 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BA4SB UT WOS:000336207500010 PM 24641557 ER PT S AU Brown, TM Fee, E AF Brown, Theodore M. Fee, Elizabeth BE Fielding, JE TI Social Movements in Health SO ANNUAL REVIEW OF PUBLIC HEALTH, VOL 35 SE Annual Review of Public Health LA English DT Review; Book Chapter DE political mobilization; reform activism; urban conditions; child health; substance abuse ID PUBLIC-HEALTH; UNITED-STATES; AMERICA; HISTORY; CARE AB Most public health practitioners know that public health has relied on biomedical advances and administrative improvements, but it is less commonly understood that social movements in health have also been sources of motivation for population health advances. This review considers the impacts of social movements focused on urban conditions and health, on the health of children, and on behavioral and substance-related determinants of health and illustrates how these movements have significantly influenced public health activities and programs. We hope this review will motivate public health workers to make common cause with social activists and to encourage social activists to ally with public health professionals. C1 [Brown, Theodore M.] Univ Rochester, Dept Hist, Rochester, NY 14627 USA. [Brown, Theodore M.] Univ Rochester, Dept Publ Hlth Sci, Rochester, NY 14627 USA. [Fee, Elizabeth] Natl Lib Med, Bethesda, MD 20894 USA. RP Brown, TM (reprint author), Univ Rochester, Dept Hist, 601 Elmwood Ave, Rochester, NY 14627 USA. EM Theodore_Brown@urmc.rochester.edu; feee@mail.nih.gov NR 105 TC 10 Z9 10 U1 1 U2 7 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0163-7525 BN 978-0-8243-2735-4 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2014 VL 35 BP 385 EP 398 DI 10.1146/annurev-publhealth-031912-114356 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BA4SB UT WOS:000336207500023 PM 24328986 ER PT S AU Stange, KC Etz, RS Gullett, H Sweeney, SA Miller, WL Jaen, CR Crabtree, BF Nutting, PA Glasgow, RE AF Stange, Kurt C. Etz, Rebecca S. Gullett, Heidi Sweeney, Sarah A. Miller, William L. Jaen, Carlos Roberto Crabtree, Benjamin F. Nutting, Paul A. Glasgow, Russell E. BE Fielding, JE TI Metrics for Assessing Improvements in Primary Health Care SO ANNUAL REVIEW OF PUBLIC HEALTH, VOL 35 SE Annual Review of Public Health LA English DT Review; Book Chapter DE primary care; primary health care; measurement; metrics; quality improvement; family; community; population health ID REINVENTING PRIMARY-CARE; AMBULATORY MEDICAL-CARE; SHARED DECISION-MAKING; CHRONIC ILLNESS; FAMILY-PRACTICE; UNITED-STATES; SENSITIVE CONDITIONS; QUALITY IMPROVEMENT; PHYSICIAN-PAYMENT; GENERAL-PRACTICE AB Metrics focus attention on what is important. Balanced metrics of primary health care inform purpose and aspiration as well as performance. Purpose in primary health care is about improving the health of people and populations in their community contexts. It is informed by metrics that include long-term, meaning- and relationship-focused perspectives. Aspirational uses of metrics inspire evolving insights and iterative improvement, using a collaborative, developmental perspective. Performance metrics assess the complex interactions among primary care tenets of accessibility, a whole-person focus, integration and coordination of care, and ongoing relationships with individuals, families, and communities; primary health care principles of inclusion and equity, a focus on people's needs, multilevel integration of health, collaborative policy dialogue, and stakeholder participation; basic and goal-directed health care, prioritization, development, and multilevel health outcomes. Environments that support reflection, development, and collaborative action are necessary for metrics to advance health and minimize unintended consequences. C1 [Stange, Kurt C.; Gullett, Heidi; Sweeney, Sarah A.] Case Western Reserve Univ, Sch Med, Dept Family Med & Community Hlth, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Stange, Kurt C.] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Dept Epidemiol & Biostat,Dept Sociol, Cleveland, OH 44106 USA. [Etz, Rebecca S.] Virginia Commonwealth Univ, Med Ctr, ACORN, Dept Family Med & Populat Hlth, Richmond, VA 23298 USA. [Sweeney, Sarah A.] Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Miller, William L.] Lehigh Valley Hlth Network, Dept Family Med, Allentown, PA 18105 USA. [Jaen, Carlos Roberto] Univ Texas Hlth Sci Ctr San Antonio, Dept Family, San Antonio, TX 78229 USA. [Jaen, Carlos Roberto] Univ Texas Hlth Sci Ctr San Antonio, Dept Community Med Family Epidemiol & Biostat, San Antonio, TX 78229 USA. [Jaen, Carlos Roberto] Univ Texas Hlth Sci Ctr San Antonio, Sch Publ Hlth, San Antonio, TX 78229 USA. [Crabtree, Benjamin F.] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Family Med & Community Hlth, Somerset, NJ 08873 USA. [Nutting, Paul A.] Univ Colorado, Hlth Sci Ctr, Dept Family Med, Ctr Res Strategies, Aurora, CO 80045 USA. [Glasgow, Russell E.] NCI, Implementat Sci Team, Div Canc Control & Populat Sci, Dept Family Med, Aurora, CO 80045 USA. [Glasgow, Russell E.] Univ Colorado, Sch Med, Colorado Hlth Outcomes Program, Aurora, CO 80045 USA. RP Stange, KC (reprint author), Case Western Reserve Univ, Sch Med, Dept Family Med & Community Hlth, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. EM kcs@case.edu; rsetz@vcu.edu; heidi.gullett@case.edu; sas223@case.edu; william.miller@lvhn.org; jaen@uthscsa.edu; crabtrbf@rutgers.edu; Paul.Nutting@CRSLLC.org; Russell.Glasgow@ucdenver.edu FU NCI NIH HHS [K05 CA140237] NR 160 TC 9 Z9 9 U1 6 U2 15 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0163-7525 BN 978-0-8243-2735-4 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2014 VL 35 BP 423 EP 442 DI 10.1146/annurev-publhealth-032013-182438 PG 20 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BA4SB UT WOS:000336207500025 PM 24641561 ER PT J AU Rothwax, JT George, AK Wood, BJ Pinto, PA AF Rothwax, Jason T. George, Arvin K. Wood, Bradford J. Pinto, Peter A. TI Multiparametric MRI in Biopsy Guidance for Prostate Cancer: Fusion-Guided SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID RESONANCE-ULTRASOUND FUSION; RADICAL PROSTATECTOMY; TARGETED BIOPSIES; NEGATIVE BIOPSY; FOCAL THERAPY; REPEAT BIOPSY; IMAGE FUSION; SYSTEM; ANTIGEN; BRACHYTHERAPY AB Prostate cancer (PCa) is the most common solid-organ malignancy among American men and the second most deadly. Current guidelines recommend a 12-core systematic biopsy following the finding of an elevated serum prostate-specific antigen (PSA). However, this strategy fails to detect an unacceptably high percentage of clinically significant cancers, leading researchers to develop new, innovative methods to improve the effectiveness of prostate biopsies. Multiparametric-MRI (MP-MRI) has emerged as a promising instrument in identifying suspicious regions within the prostate that require special attention on subsequent biopsy. Fusion platforms, which incorporate the MP-MRI into the biopsy itself and provide active targets within real-time imaging, have shown encouraging results in improving the detection rate of significant cancer. Broader applications of this technology, including MRI-guided focal therapy for prostate cancer, are in early phase trials. C1 [Rothwax, Jason T.; George, Arvin K.; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Wood, Bradford J.; Pinto, Peter A.] NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA. RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. EM pintop@mail.nih.gov NR 52 TC 14 Z9 14 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 439171 DI 10.1155/2014/439171 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AM3ZF UT WOS:000339790600001 ER PT J AU Yang, WS Yang, Y Yang, G Chow, WH Li, HL Gao, YT Ji, BT Rothman, N Zheng, W Shu, XO Xiang, YB AF Yang, Wan-Shui Yang, Yang Yang, Gong Chow, Wong-Ho Li, Hong-Lan Gao, Yu-Tang Ji, Bu-Tian Rothman, Nat Zheng, Wei Shu, Xiao-Ou Xiang, Yong-Bing TI Pre-existing type 2 diabetes and risk of lung cancer: a report from two prospective cohort studies of 133 024 Chinese adults in urban Shanghai SO BMJ OPEN LA English DT Article ID PHYSICAL-ACTIVITIES; MELLITUS; WOMEN; MEN; GLUCOSE; HEALTH; POPULATION; PREVALENCE; COMPENDIUM; MORTALITY AB Objectives: Observational studies of type 2 diabetes (T2D) and lung cancer risk are limited and controversial. We thus examined the association between T2D and risk of incident lung cancer using a cohort design. Setting: Data from two ongoing population-based cohorts (the Shanghai Men's Health Study, SMHS, 2002-2006 and the Shanghai Women's Health Study, SWHS, 1996-2000) were used. Cox proportional-hazards regression models with T2D as a time-varying exposure were modelled to estimate HRs and 95% CIs. Participants: The study population included 61 491 male participants aged 40-74 years from SMHS and 74 941 female participants aged 40-70 years from SWHS. Outcome measure: Lung cancer cases were identified through annual record linkage to the Shanghai Cancer Registry and Shanghai Municipal Registry of Vital Statistics, and were further verified through home visits and a review of medical charts by clinical and/or pathological experts. Outcome data until 31 December 2010 for men and women were used for the present analysis. Results: After a median follow-up of 6.3 years for SMHS and 12.2 years for SWHS, incident lung cancer cases were detected in 492 men and 525 women. A null association between T2D and lung cancer risk was observed in men (HR=0.87, 95% CI 0.62 to 1.21) and women (HR=0.92, 95% CI 0.69 to 1.24) after adjustments for potential confounders. Similar results were observed among never smokers. Conclusions: There is little evidence that pre-existing T2D may influence the incidence of lung cancer. C1 [Yang, Wan-Shui; Yang, Yang; Li, Hong-Lan; Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Jiaotong Univ Sch Med, Shanghai Canc Inst, Renji Hosp, Dept Epidemiol, Shanghai, Peoples R China. [Yang, Wan-Shui; Yang, Yang; Xiang, Yong-Bing] Shanghai Jiaotong Univ Sch Med, Shanghai Canc Inst, Renji Hosp, State Key Lab Oncogene & Related Genes, Shanghai, Peoples R China. [Yang, Wan-Shui] Jiujiang Univ, Sch Basic Med Sci, Dept Social Sci & Publ Hlth, Jiujiang, Peoples R China. [Yang, Gong] Vanderbilt Univ Sch Med, Div Epidemiol, Dept Med, Vanderbilt Epidemiol Ctr,Vanderbilt Ingram Canc C, Nashville, TN USA. [Chow, Wong-Ho; Zheng, Wei; Shu, Xiao-Ou] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA. [Ji, Bu-Tian; Rothman, Nat] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Xiang, YB (reprint author), Shanghai Jiaotong Univ Sch Med, Shanghai Canc Inst, Renji Hosp, Dept Epidemiol, Shanghai, Peoples R China. EM ybxiang@shsci.org FU US National Institutes of Health [R37 CA070867, R01 CA82729]; Key Discipline and Specialty Foundation of Shanghai Municipal Commission of Health and Family Planning FX This work was supported by the US National Institutes of Health (grant number R37 CA070867 and R01 CA82729); the fund of Key Discipline and Specialty Foundation of Shanghai Municipal Commission of Health and Family Planning. NR 40 TC 4 Z9 4 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2014 VL 4 IS 7 AR e004875 DI 10.1136/bmjopen-2014-004875 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AM2ZS UT WOS:000339720900022 PM 24993754 ER PT S AU Lee, LC Gao, SJ Li, QN Luo, J AF Lee, Liam Changwoo Gao, Shaojian Li, Qiuning Luo, Ji BE Wajapeyee, N TI Using Pooled miR30-shRNA Library for Cancer Lethal and Synthetic Lethal Screens SO CANCER GENOMICS AND PROTEOMICS: METHODS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE RNAi; Synthetic lethality; Cancer cells; miR30-based library; Dropout screen ID LENTIVIRAL RNAI LIBRARY; SHRNA LIBRARIES; TUMOR SUPPRESSORS; INTERFERENCE; GENES; MOUSE AB Pooled shRNA library is a powerful, rapid, and cost-effective technology to carry out functional genomic screens in mammalian cells. This approach has been applied extensively to identify genetic dependencies in cancer cells that might be exploited for therapeutic purposes. In this chapter we provide a detailed protocol for using the Hannon-Elledge miR30-based library to conduct dropout screens in cancer cell lines. This protocol is readily adaptable to other pooled shRNA libraries and should facilitate the functional annotation of the human genome. C1 [Lee, Liam Changwoo; Gao, Shaojian; Luo, Ji] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Li, Qiuning] Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China. RP Lee, LC (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 16 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0992-6; 978-1-4939-0991-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1176 BP 45 EP 58 DI 10.1007/978-1-4939-0992-6_5 D2 10.1007/978-1-4939-0992-6 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity; Pathology SC Biochemistry & Molecular Biology; Genetics & Heredity; Pathology GA BA9QH UT WOS:000339721100006 PM 25030918 ER PT S AU Bernal, F Katz, SG AF Bernal, Federico Katz, Samuel G. BE Wajapeyee, N TI Synthesis of Stabilized Alpha-Helical Peptides SO CANCER GENOMICS AND PROTEOMICS: METHODS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Stapled peptides; NMR; Protein-protein interactions; Olefin metathesis; Alpha helix ID PROTEIN-PROTEIN INTERACTIONS; RING-CLOSING METATHESIS; DESIGN; REACTIVATION; P53 AB Stabilized alpha-helical (SAH) peptides are valuable laboratory tools to explore important protein-protein interactions. Whereas most peptides lose their secondary structure when isolated from the host protein, stapled peptides incorporate an all-hydrocarbon "staple" that reinforces their natural alpha-helical structure. Thus, stapled peptides retain their functional ability to bind their native protein targets and serve multiple experimental uses. First, they are useful for structural studies such as NMR or crystal structures that map and better define binding sites. Second, they can be used to identify small molecules that specifically target that interaction site. Third, stapled peptides can be used to test the importance of specific amino acid residues or posttranslational modifications to the binding. Fourth, they can serve as structurally competent bait to identify novel binding partners to specific alpha-helical motifs. In addition to markedly improved alpha-helicity, stapled peptides also display resistance to protease cleavage and enhanced cell permeability. Most importantly, they are useful for intracellular experiments that explore the functional consequences of blocking particular protein interactions. Because of their remarkable stability, stapled peptides can be applied to whole-animal, in vivo studies. Here we describe a protocol for the synthesis of a peptide that incorporates an all-hydrocarbon "staple" employing a ring-closing olefin metathesis reaction. With proper optimization, stapled peptides can be a fundamental, accurate laboratory tool in the modern chemical biologist's armory. C1 [Bernal, Federico] NCI, Metab Branch, Ctr Canc Res, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Katz, Samuel G.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. RP Bernal, F (reprint author), NCI, Metab Branch, Ctr Canc Res, US Natl Inst Hlth, Bethesda, MD 20892 USA. NR 22 TC 3 Z9 3 U1 3 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0992-6; 978-1-4939-0991-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1176 BP 107 EP 114 DI 10.1007/978-1-4939-0992-6_9 D2 10.1007/978-1-4939-0992-6 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity; Pathology SC Biochemistry & Molecular Biology; Genetics & Heredity; Pathology GA BA9QH UT WOS:000339721100010 PM 25030922 ER PT J AU Berger, SS Elliott, C Ranzenhofer, LM Shomaker, LB Hannallah, L Field, SE Young, JF Sbrocco, T Wilfley, DE Yanovski, JA Tanofsky-Kraff, M AF Berger, Sarah Shafer Elliott, Camden Ranzenhofer, Lisa M. Shomaker, Lauren B. Hannallah, Louise Field, Sara E. Young, Jami F. Sbrocco, Tracy Wilfley, Denise E. Yanovski, Jack A. Tanofsky-Kraff, Marian TI Interpersonal problem areas and alexithymia in adolescent girls with loss of control eating SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID DEPRESSIVE SYMPTOMS; HEALTH-PROBLEMS; OBESE WOMEN; DISORDER; CHILDREN; OUTPATIENTS; RISK; MEDIATION; SCALE; GAIN AB This study investigated the links among interpersonal problem areas, depression, and alexithymia in adolescent girls at high risk for excessive weight gain and binge eating disorder. Participants were 56 girls (M-age = 14.30, SD = 1.56; 53% non-Hispanic White) with a body mass index (BMI, kg/m(2)) between the 75th and 97th percentiles (M-BMI (z) = 1.57, SD = 0.32). By design, all participants reported loss of control eating patterns in the past month. Adolescents were individually interviewed prior to participating in a group interpersonal psychotherapy obesity and eating disorder prevention program, termed IPT for the prevention of excessive weight gain (IPT-WG). Participants' interpersonal problem areas were coded by trained raters. Participants also completed questionnaires assessing depression and alexithymia. Primary interpersonal problem areas were categorized as interpersonal deficits [as defined in the eating disorders (ED) literature] (n = 29), role disputes (n = 22), or role transitions (n = 5). Girls with interpersonal deficits ED had greater depressive symptoms and alexithymia than girls with role disputes (p's <= 0.01). However, girls with role transitions did not differ from girls with interpersonal deficits-ED or role disputes. Interpersonal problem area had an indirect association with depression via alexithymia; interpersonal deficits ED were related to greater alexithymia, which in turn, was related to greater depressive symptoms (p = 0.01). Among girls at risk for excess weight gain and eating disorders, those with interpersonal deficits-ED appear to have greater distress as compared to girls with role disputes or role transitions. Future research is required to elucidate the impact of interpersonal problem areas on psychotherapy outcomes. (C) 2014 Elsevier Inc. All rights reserved. C1 [Berger, Sarah Shafer; Elliott, Camden; Ranzenhofer, Lisa M.; Shomaker, Lauren B.; Hannallah, Louise; Field, Sara E.; Sbrocco, Tracy; Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Berger, Sarah Shafer; Elliott, Camden; Ranzenhofer, Lisa M.; Shomaker, Lauren B.; Hannallah, Louise; Field, Sara E.; Yanovski, Jack A.; Tanofsky-Kraff, Marian] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Bethesda, MD 20892 USA. [Young, Jami F.] Rutgers State Univ, Piscataway, NJ USA. [Wilfley, Denise E.] Washington Univ, Sch Med, St Louis, MO USA. RP Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM marian.tanofsky-kraff@usuhs.edu OI Yanovski, Jack/0000-0001-8542-1637 FU NIDDK [1R01DK080906-01A1]; USUHS [R072IC]; NIH, NICHD Intramural Research Program [ZIA-HD-00641] FX This research was supported by NIDDK grant 1R01DK080906-01A1 and USUHS grant R072IC (to M. Tanofsky-Kraff) and NIH, NICHD Intramural Research Program ZIA-HD-00641 (to J. Yanovski). Disclaimer: The opinions and assertions expressed herein are those of the authors and are not to be construed as reflecting the views of USUHS or the US Department of Defense. NR 64 TC 5 Z9 5 U1 5 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X EI 1532-8384 J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JAN PY 2014 VL 55 IS 1 BP 170 EP 178 DI 10.1016/j.comppsych.2013.08.005 PG 9 WC Psychiatry SC Psychiatry GA AM5VO UT WOS:000339929300021 PM 24139852 ER PT B AU Donovan, C Hester, M AF Donovan, Catherine Hester, Marianne BA Donovan, C Hester, M BF Donovan, C Hester, M TI What is the problem? SO DOMESTIC VIOLENCE AND SEXUALITY: WHAT'S LOVE GOT TO DO WITH IT? LA English DT Article; Book Chapter C1 [Donovan, Catherine] Univ Sunderland, Sunderland SR2 7EE, Durham, England. [Hester, Marianne] Univ Bristol, Bristol BS8 1TH, Avon, England. [Hester, Marianne] NIMH, Bethesda, MD USA. RP Donovan, C (reprint author), Univ Sunderland, Sunderland SR2 7EE, Durham, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU POLICY PRESS PI BRISTOL PA UNIV BRISTOL, 4TH FLOOR, BEACON HOUSE, QUEENS ROAD, BRISTOL, BS8 1QU, ENGLAND BN 978-1-44731-163-8; 978-1-44730-743-3 PY 2014 BP 1 EP + PG 51 WC Family Studies; Psychology, Applied; Social Sciences, Interdisciplinary SC Family Studies; Psychology; Social Sciences - Other Topics GA BA9IK UT WOS:000339442200001 ER PT B AU Donovan, C Hester, M AF Donovan, Catherine Hester, Marianne BA Donovan, C Hester, M BF Donovan, C Hester, M TI How we did the research: the COHSAR research approach SO DOMESTIC VIOLENCE AND SEXUALITY: WHAT'S LOVE GOT TO DO WITH IT? LA English DT Article; Book Chapter C1 [Donovan, Catherine] Univ Sunderland, Sunderland SR2 7EE, Durham, England. [Hester, Marianne] Univ Bristol, Bristol BS8 1TH, Avon, England. [Hester, Marianne] NIMH, Bethesda, MD USA. RP Donovan, C (reprint author), Univ Sunderland, Sunderland SR2 7EE, Durham, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU POLICY PRESS PI BRISTOL PA UNIV BRISTOL, 4TH FLOOR, BEACON HOUSE, QUEENS ROAD, BRISTOL, BS8 1QU, ENGLAND BN 978-1-44731-163-8; 978-1-44730-743-3 PY 2014 BP 35 EP 55 PG 21 WC Family Studies; Psychology, Applied; Social Sciences, Interdisciplinary SC Family Studies; Psychology; Social Sciences - Other Topics GA BA9IK UT WOS:000339442200002 ER PT B AU Donovan, C Hester, M AF Donovan, Catherine Hester, Marianne BA Donovan, C Hester, M BF Donovan, C Hester, M TI Setting the context: sexuality matters SO DOMESTIC VIOLENCE AND SEXUALITY: WHAT'S LOVE GOT TO DO WITH IT? LA English DT Article; Book Chapter C1 [Donovan, Catherine] Univ Sunderland, Sunderland SR2 7EE, Durham, England. [Hester, Marianne] Univ Bristol, Bristol BS8 1TH, Avon, England. [Hester, Marianne] NIMH, Bethesda, MD USA. RP Donovan, C (reprint author), Univ Sunderland, Sunderland SR2 7EE, Durham, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU POLICY PRESS PI BRISTOL PA UNIV BRISTOL, 4TH FLOOR, BEACON HOUSE, QUEENS ROAD, BRISTOL, BS8 1QU, ENGLAND BN 978-1-44731-163-8; 978-1-44730-743-3 PY 2014 BP 57 EP 87 PG 31 WC Family Studies; Psychology, Applied; Social Sciences, Interdisciplinary SC Family Studies; Psychology; Social Sciences - Other Topics GA BA9IK UT WOS:000339442200003 ER PT B AU Donovan, C Hester, M AF Donovan, Catherine Hester, Marianne BA Donovan, C Hester, M BF Donovan, C Hester, M TI Identifying and experiencing domestic violence and abuse SO DOMESTIC VIOLENCE AND SEXUALITY: WHAT'S LOVE GOT TO DO WITH IT? LA English DT Article; Book Chapter C1 [Donovan, Catherine] Univ Sunderland, Sunderland SR2 7EE, Durham, England. [Hester, Marianne] Univ Bristol, Bristol BS8 1TH, Avon, England. [Hester, Marianne] NIMH, Bethesda, MD USA. RP Donovan, C (reprint author), Univ Sunderland, Sunderland SR2 7EE, Durham, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU POLICY PRESS PI BRISTOL PA UNIV BRISTOL, 4TH FLOOR, BEACON HOUSE, QUEENS ROAD, BRISTOL, BS8 1QU, ENGLAND BN 978-1-44731-163-8; 978-1-44730-743-3 PY 2014 BP 89 EP 119 PG 31 WC Family Studies; Psychology, Applied; Social Sciences, Interdisciplinary SC Family Studies; Psychology; Social Sciences - Other Topics GA BA9IK UT WOS:000339442200004 ER PT B AU Donovan, C Hester, M AF Donovan, Catherine Hester, Marianne BA Donovan, C Hester, M BF Donovan, C Hester, M TI What's love got to do with it? SO DOMESTIC VIOLENCE AND SEXUALITY: WHAT'S LOVE GOT TO DO WITH IT? LA English DT Article; Book Chapter C1 [Donovan, Catherine] Univ Sunderland, Sunderland SR2 7EE, Durham, England. [Hester, Marianne] Univ Bristol, Bristol BS8 1TH, Avon, England. [Hester, Marianne] NIMH, Bethesda, MD USA. RP Donovan, C (reprint author), Univ Sunderland, Sunderland SR2 7EE, Durham, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU POLICY PRESS PI BRISTOL PA UNIV BRISTOL, 4TH FLOOR, BEACON HOUSE, QUEENS ROAD, BRISTOL, BS8 1QU, ENGLAND BN 978-1-44731-163-8; 978-1-44730-743-3 PY 2014 BP 121 EP 156 PG 36 WC Family Studies; Psychology, Applied; Social Sciences, Interdisciplinary SC Family Studies; Psychology; Social Sciences - Other Topics GA BA9IK UT WOS:000339442200005 ER PT B AU Donovan, C Hester, M AF Donovan, Catherine Hester, Marianne BA Donovan, C Hester, M BF Donovan, C Hester, M TI Barriers to help-seeking: the gap of trust SO DOMESTIC VIOLENCE AND SEXUALITY: WHAT'S LOVE GOT TO DO WITH IT? LA English DT Article; Book Chapter C1 [Donovan, Catherine] Univ Sunderland, Sunderland SR2 7EE, Durham, England. [Hester, Marianne] Univ Bristol, Bristol BS8 1TH, Avon, England. [Hester, Marianne] NIMH, Bethesda, MD USA. RP Donovan, C (reprint author), Univ Sunderland, Sunderland SR2 7EE, Durham, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU POLICY PRESS PI BRISTOL PA UNIV BRISTOL, 4TH FLOOR, BEACON HOUSE, QUEENS ROAD, BRISTOL, BS8 1QU, ENGLAND BN 978-1-44731-163-8; 978-1-44730-743-3 PY 2014 BP 157 EP 194 PG 38 WC Family Studies; Psychology, Applied; Social Sciences, Interdisciplinary SC Family Studies; Psychology; Social Sciences - Other Topics GA BA9IK UT WOS:000339442200006 ER PT B AU Donovan, C Hester, M AF Donovan, Catherine Hester, Marianne BA Donovan, C Hester, M BF Donovan, C Hester, M TI Key findings and implications for practice SO DOMESTIC VIOLENCE AND SEXUALITY: WHAT'S LOVE GOT TO DO WITH IT? LA English DT Article; Book Chapter C1 [Donovan, Catherine] Univ Sunderland, Sunderland SR2 7EE, Durham, England. [Hester, Marianne] Univ Bristol, Bristol BS8 1TH, Avon, England. [Hester, Marianne] NIMH, Bethesda, MD USA. RP Donovan, C (reprint author), Univ Sunderland, Sunderland SR2 7EE, Durham, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU POLICY PRESS PI BRISTOL PA UNIV BRISTOL, 4TH FLOOR, BEACON HOUSE, QUEENS ROAD, BRISTOL, BS8 1QU, ENGLAND BN 978-1-44731-163-8; 978-1-44730-743-3 PY 2014 BP 195 EP 216 PG 22 WC Family Studies; Psychology, Applied; Social Sciences, Interdisciplinary SC Family Studies; Psychology; Social Sciences - Other Topics GA BA9IK UT WOS:000339442200007 ER PT B AU Horowitz, TS AF Horowitz, Todd S. BE Metzler, R Oshanin, G Redner, S TI Exit Strategies: Visual Search and the Quitting Time Problem SO FIRST-PASSAGE PHENOMENA AND THEIR APPLICATIONS LA English DT Article; Book Chapter ID MARGINAL VALUE THEOREM; HIGH-LEVEL POP; RARE TARGETS; LABORATORY ENVIRONMENT; CORRECTABLE SEARCH; MULTIPLE TARGETS; DECISION-MAKING; CERVICAL-CANCER; SET-SIZE; ATTENTION AB Visual search is the study of how humans find desired objects in their visual environment. I provide brief outline of work on visual search, and then describe work on specific topics such as the effects of target prevalence and visual foraging. C1 NCI, Basic Biobehav & Psychol Sci Branch, Rockville, MD 20850 USA. RP Horowitz, TS (reprint author), NCI, Basic Biobehav & Psychol Sci Branch, Rockville, MD 20850 USA. EM todd.horowitz@nih.gov NR 111 TC 1 Z9 1 U1 1 U2 5 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-9-81-459029-7; 978-9-81-459028-0 PY 2014 BP 390 EP 415 D2 10.1142/9104 PG 26 WC Mathematics, Applied; Physics, Mathematical; Statistics & Probability SC Mathematics; Physics GA BA8NG UT WOS:000338304200017 ER PT B AU Hawkins, DS Leary, S Bagatell, R Merchant, M Aerts, I AF Hawkins, Douglas S. Leary, Sarah Bagatell, Rochelle Merchant, Melinda Aerts, Isabelle BE Smith, FO Reaman, GH Racadio, JM TI Solid Tumors SO HEMATOPOIETIC CELL TRANSPLANTATION IN CHILDREN WITH CANCER SE Pediatric Oncology LA English DT Article; Book Chapter ID STEM-CELL RESCUE; HIGH-DOSE CHEMOTHERAPY; CHILDRENS-ONCOLOGY-GROUP; HIGH-RISK NEUROBLASTOMA; BONE-MARROW-TRANSPLANTATION; CENTRAL-NERVOUS-SYSTEM; SOFT-TISSUE SARCOMA; PHASE-II WINDOW; PRIMITIVE NEUROECTODERMAL TUMORS; INTENSIVE INDUCTION CHEMOTHERAPY C1 [Hawkins, Douglas S.; Leary, Sarah] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Bagatell, Rochelle] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Merchant, Melinda] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Aerts, Isabelle] Inst Curie, Dept Pediat, Paris, France. RP Hawkins, DS (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle Childrens Hosp, Seattle, WA 98195 USA. EM doug.hawkins@seattlechildrens.org NR 265 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-642-39920-6; 978-3-642-39919-0 J9 PEDIATR ONCOL-BERLIN PY 2014 BP 303 EP 349 DI 10.1007/978-3-642-39920-6_11 D2 10.1007/978-3-642-39920-6 PG 47 WC Oncology; Pediatrics SC Oncology; Pediatrics GA BA9JP UT WOS:000339484900012 ER PT J AU Zaman, S Sukhodolets, K Wang, P Qin, J Levens, D Agarwal, SK Marx, SJ AF Zaman, Shadia Sukhodolets, Karen Wang, Patricia Qin, Jun Levens, David Agarwal, Sunita K. Marx, Stephen J. TI FBP1 Is an Interacting Partner of Menin SO INTERNATIONAL JOURNAL OF ENDOCRINOLOGY LA English DT Article ID FAR UPSTREAM ELEMENT; HISTONE METHYLTRANSFERASE COMPLEX; MULTIPLE-ENDOCRINE-NEOPLASIA; C-MYC; BINDING PROTEIN-1; EXPRESSION; CELLS; GENE; MLL; OVEREXPRESSION AB Multiple endocrine neoplasia type 1 (MEN1) is a syndrome characterized by tumors in multiple endocrine tissues such as the parathyroid glands, the pituitary gland, and the enteropancreatic neuroendocrine tissues. MEN1 is usually caused by mutations in the MEN1 gene that codes for the protein menin. Menin interacts with proteins that regulate transcription, DNA repair and processing, and maintenance of cytoskeletal structure. We describe the identification of FBP1 as an interacting partner of menin in a large-scale pull-down assay that also immunoprecipitated RBBP5, ASH2, and LEDGF, which are members of complex proteins associated with SET1 (COMPASS), a protein complex that methylates histone H3. This interaction was confirmed by coimmunoprecipitation and Flag-pull-down assays. Furthermore, menin localized to the FUSE site on the MYC promoter, a site that is transactivated by FBP1. This investigation therefore places menin in a pathway that regulates MYC gene expression and has important implications for the biological function of menin. C1 [Zaman, Shadia; Sukhodolets, Karen; Wang, Patricia; Agarwal, Sunita K.; Marx, Stephen J.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. [Qin, Jun] Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA. [Qin, Jun] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Levens, David] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Marx, SJ (reprint author), NIDDK, Metab Dis Branch, NIH, Bldg 10,Room 9C-103,9000 Rockville, Bethesda, MD 20892 USA. EM marxs@mail.nih.gov RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 FU NIDDK; NCI FX The authors thank Dr. F. Collins and Dr. S. C. Chandrasekharappa for helpful discussions. This study was supported by funding from the intramural Program of the NIDDK and NCI. NR 29 TC 1 Z9 1 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-8337 EI 1687-8345 J9 INT J ENDOCRINOL JI Int. J. Endocrinol. PY 2014 AR 535401 DI 10.1155/2014/535401 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AM3OZ UT WOS:000339763600001 ER PT J AU Francois, B Sternberg, EM Fee, E AF Francois, Bernard Sternberg, Esther M. Fee, Elizabeth TI The Lourdes Medical Cures Revisited SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Article DE Lourdes; cures; healing; religion; prayer; tuberculosis; psycho-neuroimmunology AB This article examines the cures recorded in Lourdes, France, between 1858, the year of the Visions, and 1976, the date of the last certified cure of the twentieth century. Initially, the records of cures were crude or nonexistent, and allegations of cures were accepted without question. A Medical Bureau was established in 1883 to examine and certify the cures, and the medical methodology improved steadily in the subsequent years. We discuss the clinical criteria of the cures and the reliability of medical records. Some 1,200 cures were said to have been observed between 1858 and 1889, and about one hundred more each year during the "Golden Age" of Lourdes, 1890-1914. We studied 411 patients cured in 1909-14 and thoroughly reviewed the twenty-five cures acknowledged between 1947 and 1976. No cure has been certified from 1976 through 2006. The Lourdes phenomenon, extraordinary in many respects, still awaits scientific explanation. Lourdes concerns science as well as religion. C1 [Francois, Bernard] Univ Lyon 1, F-69005 Lyon, France. [Sternberg, Esther M.] NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Bethesda, MD 20892 USA. [Fee, Elizabeth] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Francois, B (reprint author), Univ Lyon 1, 13 Ave Debrousse, F-69005 Lyon, France. EM francoisbm@gmail.com; esternberg@email.arizona.edu; feee@mail.nih.gov FU National Library of Medicine; National Institutes of Health, National Institute of Mental Health Intramural Research Progam FX B.F. None; E. F. National Library of Medicine; E. M. S. National Institutes of Health, National Institute of Mental Health Intramural Research Progam. NR 41 TC 0 Z9 0 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 EI 1468-4373 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD JAN PY 2014 VL 69 IS 1 BP 135 EP 162 DI 10.1093/jhmas/jrs041 PG 28 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA AM6EV UT WOS:000339957000006 PM 22843835 ER PT S AU Li, NZ Chou, YY Shiee, N Chan, L Pham, DL Butman, JA AF Li, Ningzhi Chou, Yi-Yu Shiee, Navid Chan, Leighton Pham, Dzung L. Butman, John A. BE Molthen, RC Weaver, JB TI Characterizing the Spatial Distribution of Microhemorrhages Resulting from Traumatic Brain Injury SO MEDICAL IMAGING 2014: BIOMEDICAL APPLICATIONS IN MOLECULAR, STRUCTURAL, AND FUNCTIONAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Biomedical Applications in Molecular, Structural, and Functional Imaging CY FEB 16-18, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med DE Microhemorrhages; SWI; Registration; Traumatic Brain Injury; Brain Atlas; MNI space; Talairach ROI analysis AB This study examines the spatial distribution of microhemorrhages defined using susceptibility weighted images (SWI) in 46 patients with Traumatic Brain Injury (TBI) and applying region of interest (ROI) analysis using a brain atlas. SWI and 3D T1-weighted images were acquired on a 3T clinical Siemens scanner. A neuroradiologist reviewed all SWI images and manually labeled all identified microhemorrhages. To characterize the spatial distribution of microhemorrhages in standard Montreal Neurological Institute (MNI) space, the T1-weighted images were nonlinearly registered to the MNI template. This transformation was then applied to the co-registered SWI images and to the microhemorrhage coordinates. The frequencies of microhemorrhages were determined in major structures from ROIs defined in the digital Talairach brain atlas and in white matter tracts defined using a diffusion tensor imaging atlas. A total of 629 microhemorrhages were found with an average of 22 +/- 42 (range=1-179) in the 24 positive TBI patients. Microhemorrhages mostly congregated around the periphery of the brain and were fairly symmetrically distributed, although a number were found in the corpus callosum. From Talairach ROI analysis, microhemorrhages were most prevalent in the frontal lobes (65.1%). Restricting the analysis to WM tracts, microhemorrhages were primarily found in the corpus callosum (56.9%). C1 [Li, Ningzhi; Chou, Yi-Yu; Shiee, Navid; Pham, Dzung L.; Butman, John A.] Ctr Neurosci & Regenerat Med, Image Proc Core, Bethesda, MD 20814 USA. [Chan, Leighton] NIH, Dept Rehabil Med CC, Bethesda, MD 20892 USA. [Butman, John A.] NIH, Radiol & Imaging Sci Clin Ctr, Bethesda, MD 20892 USA. RP Li, NZ (reprint author), Ctr Neurosci & Regenerat Med, Image Proc Core, Bethesda, MD 20814 USA. RI Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 NR 15 TC 1 Z9 1 U1 2 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9831-1 J9 PROC SPIE PY 2014 VL 9038 AR UNSP 90381Q DI 10.1117/12.2043750 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA9HJ UT WOS:000339390900054 ER PT J AU Matlin, SL Evans, AC Tebes, JK AF Matlin, Samantha L. Evans, Arthur C., Jr. Tebes, Jacob Kraemer BE Golden, J Updike, D TI BEAUTY, CONNECTION, HEALING, AND BEHAVORIAL HEALTH: THE ROLE OF PUBLIC ART IN PROMOTING WELLNESS SO MURAL ARTS @ 30 LA English DT Article; Book Chapter C1 [Matlin, Samantha L.; Evans, Arthur C., Jr.] DBHIDS, Philadelphia, PA 19107 USA. [Matlin, Samantha L.] Yale Univ, New Haven, CT 06520 USA. [Evans, Arthur C., Jr.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Evans, Arthur C., Jr.; Tebes, Jacob Kraemer] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Evans, Arthur C., Jr.] Quinnipiac Univ, Hamden, CT USA. [Tebes, Jacob Kraemer] Yale Univ, Div Prevent & Community Res, New Haven, CT 06520 USA. [Tebes, Jacob Kraemer] Yale Univ, Consultat Ctr, New Haven, CT 06520 USA. [Tebes, Jacob Kraemer] Connecticut Mental Hlth Ctr, New Haven, CT USA. [Tebes, Jacob Kraemer] NIDA, NIH, Postdoctoral Training Program Subst Abuse Prevent, Bethesda, MD USA. [Tebes, Jacob Kraemer] Amer Psychol Assoc, Washington, DC USA. RP Matlin, SL (reprint author), DBHIDS, Philadelphia, PA 19107 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU TEMPLE UNIV PRESS PI PHILADELPHIA PA BROAD & OXFORD ST, PHILADELPHIA, PA 19122 USA PY 2014 BP 120 EP 147 PG 28 WC Art SC Art GA BA9AF UT WOS:000339064600007 ER PT J AU McDevitt, RA Reed, SJ Britt, JP AF McDevitt, Ross A. Reed, Sean J. Britt, Jonathan P. TI Optogenetics in preclinical neuroscience and psychiatry research: recent insights and potential applications SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Review DE optogenetics; depression; anxiety; addiction; obsessive-compulsive disorder ID MEDIAL PREFRONTAL CORTEX; DEEP BRAIN-STIMULATION; VENTRAL TEGMENTAL AREA; ANXIETY-RELATED BEHAVIORS; PROTEIN-COUPLED RECEPTOR; DORSAL RAPHE NUCLEUS; FORCED SWIMMING TEST; LIGHT-DRIVEN PROTON; NEURAL CIRCUITS; BASOLATERAL AMYGDALA AB There have been significant advances in the treatment of psychiatric disease in the last half century, but it is still unclear which neural circuits are ultimately responsible for specific disease states. Fortunately, technical limitations that have constrained this research have recently been mitigated by advances in research tools that facilitate circuit-based analyses. The most prominent of these tools is optogenetics, which refers to the use of genetically encoded, light-sensitive proteins that can be used to manipulate discrete neural circuits with temporal precision. Optogenetics has recently been used to examine the neural underpinnings of both psychiatric disease and symptom relief, and this research has rapidly identified novel therapeutic targets for what could be a new generation of rational drug development. As these and related methodologies for controlling neurons ultimately make their way into the clinic, circuit-based strategies for alleviating psychiatric symptoms could become a remarkably refined approach to disease treatment. C1 [McDevitt, Ross A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [Reed, Sean J.; Britt, Jonathan P.] McGill Univ, Integrated Program Neurosci, Montreal Neurol Inst, Montreal, PQ H3A 1B1, Canada. [Britt, Jonathan P.] McGill Univ, Dept Psychol, Montreal, PQ H3A 1B1, Canada. RP Britt, JP (reprint author), McGill Univ, 1205 Docteur Penfield Ave,Stewart Biol N8-9, Montreal, PQ H3A 1B1, Canada. EM jonathan.britt@mcgill.ca RI Britt, Jonathan/D-8877-2011 OI Britt, Jonathan/0000-0003-3044-9565 FU Natural Sciences and Engineering Research Council of Canada [RGPIN-2014-05069]; National Institute on Drug Abuse Intramural Research Program at the National Institutes of Health FX This research was supported by a grant from the Natural Sciences and Engineering Research Council of Canada (RGPIN-2014-05069) as well as with funding from the National Institute on Drug Abuse Intramural Research Program at the National Institutes of Health. NR 128 TC 4 Z9 4 U1 4 U2 23 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2021 J9 NEUROPSYCH DIS TREAT JI Neuropsychiatr. Dis. Treat. PY 2014 VL 10 BP 1369 EP 1379 DI 10.2147/NDT.S45896 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AM5TY UT WOS:000339924800002 PM 25092982 ER PT J AU Yi, M Zhao, YM Jia, L He, M Kebebew, E Stephens, RM AF Yi, Ming Zhao, Yongmei Jia, Li He, Mei Kebebew, Electron Stephens, Robert M. TI Performance comparison of SNP detection tools with illumina exome sequencing data-an assessment using both family pedigree information and sample-matched SNP array data SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CODING VARIATION; DISCOVERY; DISEASE; CANCER; MUTATIONS; VARIANTS; FRAMEWORK; SELECTION; ALIGNMENT; CALLER AB To apply exome-seq-derived variants in the clinical setting, there is an urgent need to identify the best variant caller(s) from a large collection of available options. We have used an Illumina exome-seq dataset as a benchmark, with two validation scenarios-family pedigree information and SNP array data for the same samples, permitting global high-throughput cross-validation, to evaluate the quality of SNP calls derived from several popular variant discovery tools from both the open-source and commercial communities using a set of designated quality metrics. To the best of our knowledge, this is the first large-scale performance comparison of exome-seq variant discovery tools using high-throughput validation with both Mendelian inheritance checking and SNP array data, which allows us to gain insights into the accuracy of SNP calling through such high-throughput validation in an unprecedented way, whereas the previously reported comparison studies have only assessed concordance of these tools without directly assessing the quality of the derived SNPs. More importantly, the main purpose of our study was to establish a reusable procedure that applies high-throughput validation to compare the quality of SNP discovery tools with a focus on exome-seq, which can be used to compare any forthcoming tool(s) of interest. C1 [Yi, Ming; Zhao, Yongmei; Jia, Li; Stephens, Robert M.] SAIC Frederick Inc, Adv Biomed Comp Ctr, Frederick Natl Lab Canc Res, Ft Detrick, MD 21702 USA. [He, Mei; Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Yi, M (reprint author), Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Res & Technol Program, Ft Detrick, MD 21702 USA. EM yiming@mail.nih.gov; stephensr@mail.nih.gov FU National Cancer Institute; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Cancer Institute; National Institutes of Health [HHSN261200800001E] FX National Cancer Institute; National Institutes of Health (Contract No. HHSN261200800001E, in whole or in part). Funding for open access charge: National Cancer Institute, National Institutes of Health (Contract No. HHSN261200800001E). NR 42 TC 12 Z9 12 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 12 AR e101 DI 10.1093/nar/gku392 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AM2XA UT WOS:000339713200005 PM 24831545 ER PT J AU Palena, C Fernando, RI Hamilton, DH AF Palena, Claudia Fernando, Romaine I. Hamilton, Duane H. TI An immunotherapeutic intervention against tumor progression Targeting a driver of the epithelial-to-mesenchymal transition SO ONCOIMMUNOLOGY LA English DT Editorial Material DE anticancer vaccines; brachyury; EMT; metastasis; therapeutic resistance ID TRANSCRIPTION FACTOR BRACHYURY; HUMAN CARCINOMA-CELLS; CANCER AB Targeting the epithelial-to-mesenchymal transition (EMT) is emerging as a novel intervention against tumor progression and metastatic dissemination, as well as the resistance to chemo-and radiotherapy displayed by multiple carcinomas. We have recently developed an immunotherapeutic approach to target a major driver of EMT, the T-box transcription factor T (also known as brachyury). This therapeutic paradigm is currently being tested in patients with advanced carcinomas in the context of a Phase I clinical trial. C1 [Palena, Claudia; Fernando, Romaine I.; Hamilton, Duane H.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Palena, C (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM palenac@mail.nih.gov NR 10 TC 11 Z9 12 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD JAN PY 2014 VL 3 IS 1 AR e27220 DI 10.4161/onci.27220 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA AM6DP UT WOS:000339952700005 ER PT J AU Sukumar, M Gattinoni, L AF Sukumar, Madhusudhanan Gattinoni, Luca TI The short and sweet of T-cell therapy Restraining glycolysis enhances the formation of immunological memory and antitumor immune responses SO ONCOIMMUNOLOGY LA English DT Editorial Material DE memory T cells; CD8+T cells; immune metabolism; glycolysis; adoptive immunotherapy ID METABOLISM AB Upon antigenic stimulation, naive CD8(+) T cells divert their bioenergetic metabolism from oxidative phosphorylation to aerobic glycolysis. This drives CD8(+) T cells to differentiate into short-lived effectors, impairing the establishment of immunological memory. The pharmacological inhibition of glycolysis with 2-deoxyglucose enhances the generation of memory CD8(+) T cells and thus improves their immunotherapeutic potential against cancer. C1 [Sukumar, Madhusudhanan] Natl Inst Hlth, Ctr Canc Res, Surg Branch, Bethesda, MD 20892 USA. [Gattinoni, Luca] Natl Inst Hlth, Expt Transplantat & Immunol Branch, Bethesda, MD USA. RP Sukumar, M (reprint author), Natl Inst Hlth, Ctr Canc Res, Surg Branch, Bethesda, MD 20892 USA. EM sukumarm2@mail.nih.gov; gattinol@mail.nih.gov RI Gattinoni, Luca/A-2281-2008 OI Gattinoni, Luca/0000-0003-2239-3282 NR 10 TC 0 Z9 0 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD JAN PY 2014 VL 3 IS 1 AR e27573 DI 10.4161/onci.27573 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA AM6DP UT WOS:000339952700036 ER PT J AU Viaud, S Daillere, R Yamazaki, T Lepage, P Boneca, I Goldszmid, R Trinchieri, G Zitvogel, L AF Viaud, Sophie Daillere, Romain Yamazaki, Takahiro Lepage, Patricia Boneca, Ivo Goldszmid, Romina Trinchieri, Giorgio Zitvogel, Laurence TI Why should we need the gut microbiota to respond to cancer therapies? SO ONCOIMMUNOLOGY LA English DT Editorial Material DE antibiotics; cancer; chemotherapy; Gram-positive bacteria; immunomodulatory regimen; microbiota; pTh17 AB Cyclophosphamide, one of the most efficient tumoricidal, antiangiogenic, and immunostimulatory drugs employed to date mediates part of its effects through intestinal bacteria, against which the host becomes immunized during treatment. Our recent work suggests that anti-commensal effector pT(H)17 and memory T(H)1 CD4(+) T-cell responses are indispensable for optimal anticancer effects as mediated by cyclophosphamide. C1 [Viaud, Sophie; Daillere, Romain; Yamazaki, Takahiro; Zitvogel, Laurence] Gustave Roussy, INSERM, U1015, Villejuif, France. [Viaud, Sophie; Daillere, Romain; Zitvogel, Laurence] Univ Paris 11, Orsay, France. [Lepage, Patricia] INRA Micalis, UMR 1319, Jouy En Josas, France. [Lepage, Patricia] Micalis, AgroParisTech, UMR 1319, Jouy En Josas, France. [Boneca, Ivo] Inst Pasteur, Unit Biol & Genet Bacterial Cell Wall, Paris, France. [Boneca, Ivo] INSERM, Grp Avenir, Paris, France. [Goldszmid, Romina; Trinchieri, Giorgio] Natl Canc Inst, Canc & Inflammat Program, Frederick, MD USA. [Zitvogel, Laurence] Gustave Roussy, Ctr Invest Clin Biotherapie CICBT 507, Villejuif, France. RP Zitvogel, L (reprint author), Gustave Roussy, INSERM, U1015, Villejuif, France. EM laurence.zitvogel@gustaveroussy.fr RI Lepage, Patricia/D-4362-2014; Boneca, Ivo/H-1677-2014 OI Boneca, Ivo/0000-0001-8122-509X NR 10 TC 2 Z9 3 U1 0 U2 11 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD JAN PY 2014 VL 3 IS 1 AR e27574 DI 10.4161/onci.27574 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA AM6DP UT WOS:000339952700037 ER PT S AU Plotnikov, SV Sabass, B Schwarz, US Waterman, CM AF Plotnikov, Sergey V. Sabass, Benedikt Schwarz, Ulrich S. Waterman, Clare M. BE Waters, JC Wittmann, T TI High-Resolution Traction Force Microscopy SO QUANTITATIVE IMAGING IN CELL BIOLOGY SE Methods in Cell Biology LA English DT Review; Book Chapter ID FOCAL ADHESIONS; SUBSTRATE STIFFNESS; CELLS; STRESSES; DISPLACEMENT; FIBROBLASTS; LOCOMOTION; MIGRATION; TENSION; MOMENTS AB Cellular forces generated by the actomyosin cytoskeleton and transmitted to the extracellular matrix (ECM) through discrete, integrin-based protein assemblies, that is, focal adhesions, are critical to developmental morphogenesis and tissue homeostasis, as well as disease progression in cancer. However, quantitative mapping of these forces has been difficult since there has been no experimental technique to visualize nanonewton forces at submicrometer spatial resolution. Here, we provide detailed protocols for measuring cellular forces exerted on two-dimensional elastic substrates with a high-resolution traction force microscopy (TFM) method. We describe fabrication of polyacrylamide substrates labeled with multiple colors of fiducial markers, functionalization of the substrates with ECM proteins, setting up the experiment, and imaging procedures. In addition, we provide the theoretical background of traction reconstruction and experimental considerations important to design a high-resolution TFM experiment. We describe the implementation of a new algorithm for processing of images of fiducial markers that are taken below the surface of the substrate, which significantly improves data quality. We demonstrate the application of the algorithm and explain how to choose a regularization parameter for suppression of the measurement error. A brief discussion of different ways to visualize and analyze the results serves to illustrate possible uses of high-resolution TFM in biomedical research. C1 [Plotnikov, Sergey V.; Waterman, Clare M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Sabass, Benedikt; Schwarz, Ulrich S.] Heidelberg Univ, Inst Theoret Phys, Heidelberg, Germany. [Sabass, Benedikt; Schwarz, Ulrich S.] Heidelberg Univ, BioQuant, Heidelberg, Germany. RP Plotnikov, SV (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Schwarz, Ulrich/K-4111-2014; OI Schwarz, Ulrich/0000-0003-1483-640X; Waterman, Clare/0000-0001-6142-6775; Sabass, Benedikt/0000-0002-7769-8043 FU Intramural NIH HHS [Z99 HL999999] NR 42 TC 17 Z9 17 U1 4 U2 23 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-420138-5 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2014 VL 123 BP 367 EP 394 DI 10.1016/B978-0-12-420138-5.00020-3 PG 28 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA BA8OU UT WOS:000338386500020 PM 24974038 ER PT J AU Candelaria-Hernandez, M AF Candelaria-Hernandez, Myrna TI Science and Trust: the need to be clear SO REVISTA DE INVESTIGACION CLINICA LA Spanish DT Letter C1 NCI, Bethesda, MD 20892 USA. RP Candelaria-Hernandez, M (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INST NACIONAL NUTRICION PI MEXICO PA VASCO DE QUIROZA 15, COLONIA SECCION XVI, TLALPAN, MEXICO 14000 D F, MEXICO SN 0034-8376 J9 REV INVEST CLIN JI Rev. Invest. Clin. PD JAN-FEB PY 2014 VL 66 IS 1 BP 95 EP 95 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AM5XA UT WOS:000339933100014 PM 24762733 ER PT J AU Robey, PG AF Robey, Pamela Gehron BE Ma, PX TI Connective tissue stem and progenitor cells SO BIOMATERIALS AND REGENERATIVE MEDICINE LA English DT Article; Book Chapter ID MARROW STROMAL CELLS; HUMAN BONE-MARROW; IN-VITRO; TRANSPLANTATION; DIFFERENTIATION; FIBROBLAST; BIOLOGY; GROWTH; MOUSE; SERUM C1 Natl Inst Hlth, Bethesda, MD 20892 USA. RP Robey, PG (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA. NR 41 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-01209-7 PY 2014 BP 34 EP 43 PG 10 WC Cell & Tissue Engineering; Materials Science, Biomaterials SC Cell Biology; Materials Science GA BA9NO UT WOS:000339619100004 ER PT S AU Khare, R Leaman, R Lu, ZY AF Khare, Ritu Leaman, Robert Lu, Zhiyong BE Kumar, VD Tipney, HJ TI Accessing Biomedical Literature in the Current Information Landscape SO BIOMEDICAL LITERATURE MINING SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Biomedical literature search; Text mining; Information retrieval; Bioinformatics; Open access; Relevance ranking; Semantic search; Text similarity search ID GOOGLE-SCHOLAR; PUBMED SEARCH; GENE ONTOLOGY; WEB SERVER; MEDLINE; TOOL; RETRIEVAL; ARTICLES; SEEKING; SCIENTISTS AB Biomedical and life sciences literature is unique because of its exponentially increasing volume and interdisciplinary nature. Biomedical literature access is essential for several types of users including biomedical researchers, clinicians, database curators, and bibliometricians. In the past few decades, several online search tools and literature archives, generic as well as biomedicine specific, have been developed. We present this chapter in the light of three consecutive steps of literature access: searching for citations, retrieving full text, and viewing the article. The first section presents the current state of practice of biomedical literature access, including an analysis of the search tools most frequently used by the users, including PubMed, Google Scholar, Web of Science, Scopus, and Embase, and a study on biomedical literature archives such as PubMed Central. The next section describes current research and the state-of-the-art systems motivated by the challenges a user faces during query formulation and interpretation of search results. The research solutions are classified into five key areas related to text and data mining, text similarity search, semantic search, query support, relevance ranking, and clustering results. Finally, the last section describes some predicted future trends for improving biomedical literature access, such as searching and reading articles on portable devices, and adoption of the open access policy. C1 [Khare, Ritu; Leaman, Robert; Lu, Zhiyong] NIH, Natl Ctr Biotechnol Informat, US Natl Lib Med, Bethesda, MD 20892 USA. RP Khare, R (reprint author), NIH, Natl Ctr Biotechnol Informat, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 LM999999] NR 76 TC 4 Z9 4 U1 3 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0709-0; 978-1-4939-0708-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1159 BP 11 EP 31 DI 10.1007/978-1-4939-0709-0_2 D2 10.1007/978-1-4939-0709-0 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA BA8RL UT WOS:000338507800003 PM 24788259 ER PT S AU Walkiewicz, MP Bui, M Quenet, D Dalal, Y AF Walkiewicz, Marcin P. Minh Bui Quenet, Delphine Dalal, Yamini BE Noguchi, E Gadaleta, MC TI Tracking Histone Variant Nucleosomes Across the Human Cell Cycle Using Biophysical, Biochemical, and Cytological Analyses SO CELL CYCLE CONTROL: MECHANISMS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE CENP-A; Histones; Cell cycle; SDS-PAGE; TAU; Western blotting; Chromatin fiber; Immunofluorescence; Atomic force microscopy; AFM ID PROTEIN-DNA COMPLEXES; CENP-A NUCLEOSOME; CHROMATIN; ORGANIZATION; CHROMOSOME; CENTROMERE; ORDER AB Histone variants such as H3.3, macroH2A, H2A.Z, and CENP-A are important epigenetic modifiers of the chromatin state in eukaryotic genomes. The centromeric histone H3 variant CENP-A/CENH3 epigenetically marks centromeres and is required for assembly of the kinetochore complex, a region of the chromosome that is responsible for proper genome segregation during mitosis. Several diverse techniques using biochemical, cell biology, and biophysical approaches have been utilized to study the nature of the CENP-A nucleosome across the cell cycle. In this chapter, we describe methods for CENP-A nucleosome purification and separation of CENP-A from other core histones using traditional SDS-PAGE and more resolving techniques such as Triton acid urea (TAU) and two-dimensional gels. We also discuss methods for observation of CENP-A on chromatin fibers using immunofluorescence. Finally, we provide a detailed description of analysis of chromatin structures using atomic force microscopy. C1 [Walkiewicz, Marcin P.; Minh Bui; Quenet, Delphine; Dalal, Yamini] NCI, Chromatin Struct & Epigenet Mech Unit, Lab Receptor Biol & Gene Express, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Walkiewicz, MP (reprint author), NCI, Chromatin Struct & Epigenet Mech Unit, Lab Receptor Biol & Gene Express, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA BC011206-01, ZIA BC011206-03, ZIA BC011206-05, ZIA BC011206-02, ZIA BC011206-06, ZIA BC011206-04] NR 22 TC 2 Z9 2 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0888-2; 978-1-4939-0887-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1170 BP 589 EP 615 DI 10.1007/978-1-4939-0888-2_34 D2 10.1007/978-1-4939-0888-2 PG 27 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA8RM UT WOS:000338508500035 PM 24906339 ER PT S AU Mukherjee, S Pierson, TC Dowd, KA AF Mukherjee, Swati Pierson, Theodore C. Dowd, Kimberly A. BE Padmanabhan, R Vasudevan, SG TI Pseudo-infectious Reporter Virus Particles for Measuring Antibody-Mediated Neutralization and Enhancement of Dengue Virus Infection SO DENGUE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Reporter virus particles (RVP); Dengue virus; Antibody neutralization; Antibody-dependent enhancement (ADE); Replicon; Flavivirus ID WEST-NILE-VIRUS; DEPENDENT ENHANCEMENT; CYCLIZATION SEQUENCES; HETEROLOGOUS GENES; REPLICON VECTORS; RNA REPLICATION; IN-VITRO; VACCINE; TYPE-2; COMPLEMENTATION AB This chapter outlines methods for the production of dengue virus (DENV) reporter virus particles (RVPs) and their use in assays that measure antibody-mediated neutralization and enhancement of DENV infection. RVPs are pseudo-infectious virions produced by complementation of a self-replicating flavivirus replicon with the DENV structural genes in trans. RVPs harvested from transfected cells are capable of only a single round of infection and encapsidate replicon RNA that encodes a reporter gene used to enumerate infected cells. RVPs may be produced using the structural genes of different DENV serotypes, genotypes, and mutants by changing plasmids used for complementation. Further modifications are possible including generating RVPs with varying levels of uncleaved prM protein, which resemble either the immature or mature form of the virus. Neutralization potency is measured by incubating RVPs with serial dilutions of antibody, followed by infection of target cells that express DENV attachment factors. Enhancement of infection is measured similarly using Fc receptor-expressing cells capable of internalizing antibody-virus complexes. C1 [Mukherjee, Swati; Pierson, Theodore C.; Dowd, Kimberly A.] NIAID, Viral Pathogenesis Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Mukherjee, S (reprint author), NIAID, Viral Pathogenesis Sect, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 55 TC 5 Z9 5 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0348-1; 978-1-4939-0347-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1138 BP 75 EP 97 DI 10.1007/978-1-4939-0348-1_6 D2 10.1007/978-1-4939-0348-1 PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Infectious Diseases; Virology SC Biochemistry & Molecular Biology; Infectious Diseases; Virology GA BA5UT UT WOS:000337028200007 PM 24696332 ER PT S AU Kasprzak, WK Shapiro, BA AF Kasprzak, Wojciech K. Shapiro, Bruce A. BE Padmanabhan, R Vasudevan, SG TI MPGAfold in Dengue Secondary Structure Prediction SO DENGUE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Dengue virus; Massively Parallel Genetic Algorithm; MPGAfold; RNA secondary structure prediction; 3 ' untranslated core region; Dumbbell structures; StructureLab workbench ID PARALLEL GENETIC ALGORITHM; WEST-NILE-VIRUS; RNA STRUCTURE-ANALYSIS; 3 UNTRANSLATED REGION; DE-NOVO SYNTHESIS; CYCLIZATION SEQUENCES; 3'-UNTRANSLATED REGION; IN-VITRO; 3'-TERMINAL REGIONS; FUNCTIONAL-ANALYSIS AB This chapter presents the computational prediction of the secondary structures within the 5' and 3' untranslated regions of the dengue virus serotype 2 (DENV2), with the focus on the conformational prediction of the two dumbbell-like structures, 5' DB and 3' DB, found in the core region of the 3' untranslated region of DENV2. For secondary structure prediction purposes we used a 719 nt-long subgenomic RNA construct from DENV2, which we refer to as the minigenome. The construct combines the 5'-most 226 nt from the 5' UTR and a fragment of the capsid coding region with the last 42 nt from the non-structural protein NS5 coding region and the 451 nt of the 3' UTR. This minigenome has been shown to contain the elements needed for translation, as well as negative strand RNA synthesis. We present the Massively Parallel Genetic Algorithm MPGAfold, a non-deterministic algorithm, that was used to predict the secondary structures of the DENV2 719 nt long minigenome construct, as well as our computational workbench called StructureLab that was used to interactively explore the solution spaces produced by MPGAfold. The MPGAfold algorithm is first introduced at the conceptual level. Then specific parameters guiding its performance are discussed and illustrated with a representative selection of the results from the study. Plots of the solution spaces generated by MPGAfold illustrate the algorithm, while selected secondary structures focus on variable formation of the dumbbell structures and other identified structural motifs. They also serve as illustrations of some of the capabilities of the StructureLab workbench. Results of the computational structure determination calculations are discussed and compared to the experimental data. C1 [Kasprzak, Wojciech K.] Leidos Biomed Res Inc, Basic Sci Program, Frederick, MD 21702 USA. [Kasprzak, Wojciech K.; Shapiro, Bruce A.] NCI, Basic Res Lab, Frederick, MD 21701 USA. RP Kasprzak, WK (reprint author), Leidos Biomed Res Inc, Basic Sci Program, Frederick, MD 21702 USA. FU Intramural NIH HHS; PHS HHS [261200800001E] NR 70 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0348-1; 978-1-4939-0347-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1138 BP 199 EP 224 DI 10.1007/978-1-4939-0348-1_13 D2 10.1007/978-1-4939-0348-1 PG 26 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Infectious Diseases; Virology SC Biochemistry & Molecular Biology; Infectious Diseases; Virology GA BA5UT UT WOS:000337028200014 PM 24696339 ER PT S AU Sztuba-Solinska, J Le Grice, SFJ AF Sztuba-Solinska, Joanna Le Grice, Stuart F. J. BE Padmanabhan, R Vasudevan, SG TI Insights into Secondary and Tertiary Interactions of Dengue Virus RNA by SHAPE SO DENGUE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Dengue virus; RNA-RNA interactions; cis-Acting RNA motifs; SHAPE ID SELECTIVE 2'-HYDROXYL ACYLATION; SINGLE NUCLEOTIDE RESOLUTION; PRIMER EXTENSION SHAPE; DE-NOVO SYNTHESIS; IN-VITRO; REPLICATION; SOFTWARE; GENOME; TRANSLATION; INITIATION AB Dengue virus (DENV) is a single-stranded positive-sense RNA virus belonging to the Flaviviridae family. The DENV RNA genome contains multiple cis-acting elements that continue to unravel their essential role in managing viral molecular processes. Attempts have been made to predict the secondary structure of DENV RNA using a variety of computational tools. Nevertheless, a greater degree of accuracy is achieved when these methods are complemented with structure probing experimentation. This chapter outlines detailed methodology for the structural study of DENV subgenomic minigenome RNA by applying high-throughput selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE). High-throughput SHAPE combines a novel chemical probing technology with reverse transcription, capillary electrophoresis, and secondary structure prediction software to rapidly and reproducibly determine the structure of RNAs from several hundred to several thousand nucleotides at single-nucleotide resolution. This methodology investigates local structure for all positions in a sequence-independent manner and as such it is particularly useful in predicting RNA secondary and tertiary interactions. C1 [Sztuba-Solinska, Joanna; Le Grice, Stuart F. J.] Frederick Natl Lab Canc Res, HIV Drug Resistance Program, RT Biochem Sect, Frederick, MD 21702 USA. RP Sztuba-Solinska, J (reprint author), Frederick Natl Lab Canc Res, HIV Drug Resistance Program, RT Biochem Sect, Frederick, MD 21702 USA. NR 24 TC 2 Z9 2 U1 1 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0348-1; 978-1-4939-0347-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1138 BP 225 EP 239 DI 10.1007/978-1-4939-0348-1_14 D2 10.1007/978-1-4939-0348-1 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Infectious Diseases; Virology SC Biochemistry & Molecular Biology; Infectious Diseases; Virology GA BA5UT UT WOS:000337028200015 PM 24696340 ER PT S AU Lacy, P Rosenberg, HF Walsh, GM AF Lacy, Paige Rosenberg, Helene F. Walsh, Garry M. BE Walsh, GM TI Eosinophil Overview: Structure, Biological Properties, and Key Functions SO EOSINOPHILS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Eosinophil; Accumulation; Apoptosis; Degranulation; Animal models ID MAJOR BASIC-PROTEIN; ANTIGEN-PRESENTING CELLS; PIECEMEAL DEGRANULATION; MOUSE EOSINOPHILS; CATIONIC PROTEIN; ALLERGIC INFLAMMATION; SCHISTOSOMA-MANSONI; TRANSGENIC MICE; FLOW CONDITIONS; EXPRESSION AB The eosinophil is an enigmatic cell with a continuing ability to fascinate. A considerable history of research endeavor on eosinophil biology stretches from the present time back to the nineteenth century. Perhaps one of the most fascinating aspects of the eosinophil is how accumulating knowledge has changed the perception of its function from passive bystander, modulator of inflammation, to potent effector cell loaded with histotoxic substances through to more recent recognition that it can act as both a positive and negative regulator of complex events in both innate and adaptive immunity. This book consists of 26 chapters written by experts in the field of eosinophil biology that provide comprehensive and clearly written protocols for techniques designed to underpin research into the function of the eosinophil in health and disease. C1 [Lacy, Paige] Univ Alberta, Dept Med, Pulm Res Grp, Edmonton, AB, Canada. [Rosenberg, Helene F.] NIAID, Lab Allerg Dis, Inflammat Immunobiol Sect, NIH, Bethesda, MD 20892 USA. [Walsh, Garry M.] Univ Aberdeen, Inst Med Sci, Sch Med & Dent, Div Appl Med, Aberdeen, Scotland. RP Lacy, P (reprint author), Univ Alberta, Dept Med, Pulm Res Grp, Edmonton, AB, Canada. NR 87 TC 6 Z9 6 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1016-8; 978-1-4939-1015-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1178 BP 1 EP 12 DI 10.1007/978-1-4939-1016-8_1 D2 10.1007/978-1-4939-1016-8 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA BA9RO UT WOS:000339772100002 PM 24986602 ER PT S AU Percopo, CM Dyer, KD Karpe, KA Domachowske, JB Rosenberg, HF AF Percopo, Caroline M. Dyer, Kimberly D. Karpe, Kendal A. Domachowske, Joseph B. Rosenberg, Helene F. BE Walsh, GM TI Eosinophils and Respiratory Virus Infection: A Dual-Standard Curve qRT-PCR-Based Method for Determining Virus Recovery from Mouse Lung Tissue SO EOSINOPHILS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Inflammation; Leukocyte; Eosinophil; Pneumonia virus of mice; Polymerase chain reaction ID LETHAL PNEUMOVIRUS INFECTION; SYNCYTIAL VIRUS; ASTHMA; PHENOTYPES; IMMUNITY; DISEASE AB Several lines of investigation have indicated a role for eosinophilic leukocytes in limiting virus infectivity and promoting virion clearance. We have established a respiratory virus infection model with pneumonia virus of mice (PVM; family Paramyxoviridae), a natural mouse pathogen that replicates the more severe forms of human disease elicited by the phylogenetically related respiratory syncytial virus (RSV). In this chapter, we present a rapid and highly reproducible dual-standard curve qRT-PCR based method for quantitative detection of PVM replication in mouse lung tissue. We have used this assay to evaluate eosinophil-mediated antiviral host defense in mouse models of cytokine and antigen-driven eosinophilic inflammation. C1 [Percopo, Caroline M.; Dyer, Kimberly D.; Karpe, Kendal A.] NIAID, Inflammat Immunobiol Sect, NIH, Bethesda, MD 20892 USA. [Domachowske, Joseph B.] SUNY Upstate Med Univ, Dept Pediat, Div Infect Dis, Syracuse, NY 13210 USA. [Rosenberg, Helene F.] NIAID, Lab Allerg Dis, Inflammat Immunobiol Sect, NIH, Bethesda, MD 20892 USA. RP Percopo, CM (reprint author), NIAID, Inflammat Immunobiol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU Intramural NIH HHS; NIAID NIH HHS [AI000941, AI000943] NR 16 TC 9 Z9 9 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1016-8; 978-1-4939-1015-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1178 BP 257 EP 266 DI 10.1007/978-1-4939-1016-8_22 D2 10.1007/978-1-4939-1016-8 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA BA9RO UT WOS:000339772100023 PM 24986623 ER PT S AU Chou, JY Mansfield, BC AF Chou, Janice Y. Mansfield, Brian C. BE Bevensee, MO TI The SLC37 Family of Sugar-Phosphate/Phosphate Exchangers SO EXCHANGERS SE Current Topics in Membranes LA English DT Review; Book Chapter ID GLYCOGEN-STORAGE-DISEASE; PUTATIVE GLUCOSE-6-PHOSPHATE TRANSLOCASE; MAJOR FACILITATOR SUPERFAMILY; PHOSPHOHISTIDINE-ENZYME INTERMEDIATE; CONGENITAL NEUTROPENIA SYNDROME; ENDOPLASMIC-RETICULUM; ESCHERICHIA-COLI; MICROSOMAL TRANSPORT; TRANSMEMBRANE PROTEINS; ANTIPORTER DEFICIENT AB The SLC37 family members are endoplasmic reticulum (ER)-associated sugar-phosphate/phosphate (P-i) exchangers. Three of the four members, SLC37A1, SLC37A2, and SLC37A4, function as P-i-linked glucose-6-phosphate (G6P) antiporters catalyzing G6P:P-i and P-i:P-i exchanges. The activity of SLC37A3 is unknown. SLC37A4, better known as the G6P transporter (G6PT), has been extensively characterized, functionally and structurally, and is the best characterized family member. G6PT contains 10 transmembrane helices with both N and C termini facing the cytoplasm. The primary in vivo function of the G6PT protein is to translocate G6P from the cytoplasm into the ER lumen where it couples with either the liver/kidney/intestine-restricted glucose-6-phosphatase-alpha (G6Pase-alpha or G6PC) or the ubiquitously expressed G6Pase-beta (or G6PC3) to hydrolyze G6P to glucose and P-i. The G6PT/G6Pase-alpha complex maintains interprandial glucose homeostasis, and the G6PT/G6Pase-beta complex maintains neutrophil energy homeostasis and functionality. G6PT is highly selective for G6P and is competitively inhibited by cholorogenic acid and its derivatives. Neither SLC37A1 nor SLC37A2 can couple functionally with G6Pase-alpha or G6Pase-beta, and the antiporter activities of SLC37A1 or SLC37A2 are not inhibited by cholorogenic acid. Deficiencies in G6PT cause glycogen storage disease type Ib (GSD-Ib), a metabolic and immune disorder. To date, 91 separate SLC37A4 mutations, including 39 missense mutations, have been identified in GSD-Ib patients. Characterization of missense mutations has yielded valuable information on functionally important residues in the G6PT protein. The biological roles of the other SLC37 proteins remain to be determined and deficiencies have not yet been correlated to diseases. C1 [Chou, Janice Y.; Mansfield, Brian C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Mansfield, Brian C.] Fdn Fighting Blindness, Columbia, MD USA. RP Chou, JY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov OI Mansfield, Brian/0000-0002-8533-2789 FU Intramural NIH HHS [ZIA HD000912-35] NR 67 TC 5 Z9 5 U1 2 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1063-5823 BN 978-0-12-800291-9; 978-0-12-800223-0 J9 CURR TOP MEMBR JI Curr. Top. Membr. PY 2014 VL 73 BP 357 EP 382 DI 10.1016/B978-0-12-800223-0.00010-4 PG 26 WC Biochemistry & Molecular Biology; Biophysics; Physiology SC Biochemistry & Molecular Biology; Biophysics; Physiology GA BA8AA UT WOS:000337917800011 PM 24745989 ER PT S AU Milberg, O Tora, M Shitara, A Takuma, T Masedunskas, A Weigert, R AF Milberg, Oleg Tora, Muhibullah Shitara, Akiko Takuma, Taishin Masedunskas, Andrius Weigert, Roberto BE Ivanov, AI TI Probing the Role of the Actin Cytoskeleton During Regulated Exocytosis by Intravital Microscopy SO EXOCYTOSIS AND ENDOCYTOSIS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Intravital microscopy; Exocytosis; Actin cytoskeleton; Membrane trafficking; Salivary glands ID F-ACTIN; LIFEACT AB The actin cytoskeleton plays a fundamental role in controlling several steps during regulated exocytosis. Here, we describe a combination of procedures that are aimed at studying the dynamics and the mechanism of the actin cytoskeleton in the salivary glands of live rodents, a model for exocrine secretion. Our approach relies on intravital microscopy, an imaging technique that enables imaging biological events in live animals at a subcellular resolution, and it is complemented by the use of pharmacological agents and indirect immunofluorescence in the salivary tissue. C1 [Milberg, Oleg; Tora, Muhibullah; Masedunskas, Andrius; Weigert, Roberto] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Shitara, Akiko; Takuma, Taishin] Hlth Sci Univ Hokkaido, Dept Oral Biol, Div Biochem, Sch Dent, Ishikari, Hokkaido 06102, Japan. RP Milberg, O (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. OI Masedunskas, Andrius/0000-0002-4533-5467 FU Intramural NIH HHS [ZIA DE000717-09] NR 16 TC 2 Z9 2 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0944-5; 978-1-4939-0943-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1174 BP 407 EP 421 DI 10.1007/978-1-4939-0944-5_28 D2 10.1007/978-1-4939-0944-5 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA8RE UT WOS:000338503100029 PM 24947398 ER PT B AU Annunziata, CM Dennis, PA AF Annunziata, Christina M. Dennis, Phillip A. BE Figg, WD McLeod, HL TI Molecular Targets SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE Drug targets; Signaling pathways; Cancer treatment ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; ACUTE LYMPHOBLASTIC-LEUKEMIA; ADP-RIBOSE POLYMERASE; PROSTATE-CANCER; BREAST-CANCER; THERAPEUTIC TARGET; KAPPA-B; HEPATOCELLULAR-CARCINOMA; ANTICANCER THERAPY AB The optimal targeting of cancer requires not only the selection of the target but also the identification of the patients whose cancer depends on the targeted pathway. The objective of this chapter is to give an overview of molecular targets in cancer therapeutics. Targets have been categorized as either established or novel types. Established targets include those against which most currently licensed anticancer drugs were developed and include DNA, microtubules, and nuclear hormone receptors. Novel targets are those under current preclinical and clinical investigation. The section on novel targets emphasizes the relationships of the novel targets to the biological traits of cancer. C1 [Annunziata, Christina M.; Dennis, Phillip A.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Annunziata, CM (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, 10 Ctr Dr,Room 12N226, Bethesda, MD 20892 USA. EM annunzic@mail.nih.gov RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 135 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 1 EP 21 DI 10.1007/978-1-4614-9135-4_1 D2 10.1007/978-1-4614-9135-4 PG 21 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300001 ER PT B AU McKee, TC Van Wyk, AWW Whitson, EL AF McKee, Tawnya C. Van Wyk, Albert W. W. Whitson, Emily L. BE Figg, WD McLeod, HL TI Natural Product Screening SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE Screening; Natural products; Assay development; Phenotypic screen; Biochemical screen; Nuisance compounds ID TUMOR-CELL-LINES; SCINTILLATION PROXIMITY ASSAY; RESONANCE ENERGY-TRANSFER; RIBONUCLEASE-H ACTIVITY; PLANT ANTITUMOR AGENTS; HIGH-THROUGHPUT; DRUG DISCOVERY; TOPOISOMERASE-I; COMBINATION CHEMOTHERAPY; MARINE-INVERTEBRATES AB Natural product screening marries the search for new medicines with the search for new molecules from natural sources. The rationale for natural products as a source for new hits from which to develop new drugs will be discussed, and a brief overview of screening methods and techniques including how these are modified for the screening of crude natural product extracts will be described. This chapter will also provide a summary of the importance of natural products to drug discovery and development, the results from screening assays developed, and the natural products isolated utilizing these screens. C1 [McKee, Tawnya C.; Van Wyk, Albert W. W.; Whitson, Emily L.] NCI, Mol Targets Lab, Mol Discovery Program, Ctr Canc Res, Frederick, MD 21701 USA. RP McKee, TC (reprint author), NCI, Mol Targets Lab, Mol Discovery Program, Ctr Canc Res, Frederick, MD 21701 USA. EM mckeeta@mail.nih.gov NR 116 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 39 EP 67 DI 10.1007/978-1-4614-9135-4_3 D2 10.1007/978-1-4614-9135-4 PG 29 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300003 ER PT B AU Kummar, S Doroshow, JH AF Kummar, Shivaani Doroshow, James H. BE Figg, WD McLeod, HL TI Phase 0 Trials in Oncology SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE Pre-phase 1 trials; Pharmacodynamically driven trials; Exploratory IND studies ID ADP-RIBOSE POLYMERASE; CLINICAL-TRIALS; DRUG DEVELOPMENT; TUMOR-BIOPSIES; ANTICANCER AGENTS; INHIBITOR; PATIENT; ABT-888 AB First-in-human clinical studies (phase I) of new anticancer agents have traditionally focused on determining the maximum tolerated dose and dose-limiting toxicities in patients with cancer. Subsequent phase II and III trials evaluate whether the new agent has potential efficacy. This process is time consuming, expensive, involves potentially hundreds of patients, and has a high rate of failure. To address some of these limitations and facilitate the development and approval of new drugs, the FDA allows phase 0 first-in-human trials to establish whether the investigational agent achieves the desired concentrations and/or modulates its target at clinically achievable concentrations. These trials administer subtherapeutic doses of drug, which are not anticipated to cause toxicity, to a small number of patients for the conduct of pharmacodynamic, pharmacokinetic, or imaging studies. If the agent demonstrates a desirable pharmacokinetic/pharmacodynamic profile, traditional phase I safety and tolerability studies are conducted; otherwise, further clinical development of the agent is unlikely to be justified. This chapter summarizes the key differences between phase 0 and phase I clinical trials. C1 [Kummar, Shivaani] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Doroshow, James H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Doroshow, JH (reprint author), NCI, Div Canc Treatment & Diag, NIH, Bldg 31,Room 3A44,31 Ctr Dr, Bethesda, MD 20892 USA. EM doroshoj@mail.nih.gov NR 24 TC 0 Z9 0 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 89 EP 97 DI 10.1007/978-1-4614-9135-4_5 D2 10.1007/978-1-4614-9135-4 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300005 ER PT B AU Gardner, ER AF Gardner, Erin R. BE Figg, WD McLeod, HL TI Quantitative Analytical Methods: Development and Clinical Considerations SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE Quantitative; Analytical; Method development; Assay; Sample; Specimen; Processing; Storage; HPLC; LC-MS-MS ID PERFORMANCE LIQUID-CHROMATOGRAPHY; HUMAN PLASMA; MASS-SPECTROMETRY; CANCER-PATIENTS; MICRODIALYSIS; IMATINIB; PHARMACOKINETICS; ULTRAVIOLET; IRINOTECAN; SAMPLES AB Accurate and precise data on drug concentrations is critical for anticancer drug development. The ability to measure anticancer agents is essential throughout the drug development process, and numerous analytical assays are typically developed-from initial purification and assessment of impurities, to in vitro transport and metabolism studies, through large-scale pharmacokinetic studies to therapeutic drug monitoring. To ensure that data generated from collected samples is representative of the actual drug concentration, it is crucial that method optimization begins early in the process and that a number of clinical considerations, including selection of analytes and matrices, sample collection volumes, and processing requirements, be evaluated prior to the start of sample collection. This chapter will focus primarily on the development process and clinical considerations relevant to quantitative analytical assays for small molecule anticancer agents with HPLC, LC-MS, or LC-MS-MS, though some considerations are applicable to all molecules under development. C1 NCI, Clin Pharmacol Program, SAIC Frederick, Frederick, MD 21702 USA. RP Gardner, ER (reprint author), NCI, Clin Pharmacol Program, SAIC Frederick, Frederick, MD 21702 USA. EM ergardner@gmail.com NR 23 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 107 EP 116 DI 10.1007/978-1-4614-9135-4_7 D2 10.1007/978-1-4614-9135-4 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300007 ER PT B AU Reed, E Larkins, TL Chau, CH Figg, WD AF Reed, Eddie Larkins, Teri L. Chau, Cindy H. Figg, William D. BE Figg, WD McLeod, HL TI DNA Repair: ERCC1, Nucleotide Excision Repair, and Platinum Resistance SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE ERCC1; Nucleotide excision repair; Hedgehog ID HUMAN OVARIAN-CANCER; MESSENGER-RNA EXPRESSION; ATOMIC-ABSORPTION-SPECTROMETRY; ACQUIRED CISPLATIN RESISTANCE; INTERSTRAND CROSS-LINKS; TUMOR-NECROSIS-FACTOR; ZINC-FINGER GENE; CELL-LINES; CARCINOMA CELLS; ANTICANCER CHEMOTHERAPY AB DNA excision repair plays a significant part in platinum-based chemotherapy by removing DNA lesions caused by platinum-containing drugs. The nucleotide excision repair (NER) pathway is the mammalian DNA repair mechanism that removes bulky DNA adducts induced by DNA damaging chemotherapeutic agents. Platinum compounds induce their cytotoxic effect by binding to a DNA molecule in the form of a platinum-DNA-adduct. The NER pathway is the main mechanism responsible for platinum resistance by increased platinum-DNA-adduct removal and the excision repair cross complementing-group 1 (ERCC1) gene plays a major role in the NER-pathway because of its damage recognition and excision ability. This chapter will review mechanisms of DNA repair and platinum resistance as it relates to the NER pathway and regulation of ERCC1. A brief discussion on the role of cancer stem cells in platinum resistance is also presented. C1 [Reed, Eddie] Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD 20892 USA. [Larkins, Teri L.] Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36604 USA. [Chau, Cindy H.; Figg, William D.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Reed, E (reprint author), Natl Inst Minor Hlth & Hlth Dispar, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA. EM eddie.reed@nih.gov RI Figg Sr, William/M-2411-2016 NR 92 TC 2 Z9 2 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 333 EP 349 DI 10.1007/978-1-4614-9135-4_18 D2 10.1007/978-1-4614-9135-4 PG 17 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300018 ER PT B AU Massey, PR Fojo, T Bates, SE AF Massey, Paul R. Fojo, Tito Bates, Susan E. BE Figg, WD McLeod, HL TI ABC Transporters: Involvement in Multidrug Resistance and Drug Disposition SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE P-glycoprotein; ABCG2; Multidrug transporters; ABC transporters ID BREAST-CANCER RESISTANCE; ACUTE MYELOID-LEUKEMIA; BLOOD-BRAIN-BARRIER; MDR1A P-GLYCOPROTEIN; SINGLE NUCLEOTIDE POLYMORPHISMS; TYROSINE KINASE INHIBITORS; BINDING CASSETTE ABC; ORGANIC ANION TRANSPORTER; SOUTHWEST-ONCOLOGY-GROUP; ADVANCED SOLID TUMORS AB ATP-binding cassette (ABC) transporters, among the largest of the transporter superfamilies, are found in normal tissues and transport a wide range of substrates important in normal physiology. One normal tissue function of these transporters is protection from toxic compounds including xenobiotics. By limiting tissue exposure to substrates, ABC transporters may contribute to the blood-brain barrier, the maternal-fetal barrier, and the mucosal barrier that limits oral absorption of compounds. Because a range of chemotherapeutic drugs have been found to be substrates for several of these transporters, many have inferred that expression of transporters in tumor cells has the potential to confer drug resistance; indeed, several transporters are referred to as multidrug transporters. This chapter will review the role of these multidrug transporters in oncology and in normal tissue. C1 [Massey, Paul R.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Fojo, Tito; Bates, Susan E.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov NR 202 TC 6 Z9 7 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 373 EP 400 DI 10.1007/978-1-4614-9135-4_20 D2 10.1007/978-1-4614-9135-4 PG 28 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300020 ER PT B AU English, BC Richardson, ED Sissung, TM AF English, Bevin C. Richardson, Emily D. Sissung, Tristan M. BE Figg, WD McLeod, HL TI High-Throughput Platforms in Drug Metabolism and Transport Pharmacogenetics SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE Genotyping; Pharmacogenetics; Platforms; Genes; ADME ID CELL LUNG-CANCER; DIHYDROPYRIMIDINE DEHYDROGENASE-DEFICIENCY; BISPHOSPHONATE-RELATED OSTEONECROSIS; GENOME-WIDE ASSOCIATION; GENETIC POLYMORPHISMS; CYP2D6 POLYMORPHISMS; CLINICAL-OUTCOMES; PATHWAY ANALYSIS; INDUCED TOXICITY; DMET PLATFORM AB Although there are now several thousand published studies that have examined the genetic contribution to interindividual variation in drug treatment (i.e., pharmacogenetics), very few have examined the large portions of the genome; rather these have focused on candidate gene and pathway-based study designs. However, multiple large-scale genotyping technologies have recently emerged that allow the researcher to examine pharmacogenetic endpoints similar to 100-500,000 SNPs at a time. Each genotyping platform is slightly different and applicable to either the clinical setting, wherein the genetic information informs treatment in patients with certain variants, or the research setting, where patients that are treated with certain drugs are either prospectively or retrospectively evaluated for genetic variants that may influence treatment outcomes. The purpose of this chapter is to describe the current study designs in pharmacogenetics, the major findings of these studies that are applied clinically, to provide an overview of commercially available large-scale genotyping technologies, and to discuss how these technologies can be applied in both clinical and research settings. While oncology agents will be the primary focus of this chapter, given that individuals undergoing therapy for cancer are often treated with multiple drugs, it is important to also consider other agents. C1 [English, Bevin C.; Richardson, Emily D.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Sissung, Tristan M.] NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Sissung, TM (reprint author), NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 5A07, Bethesda, MD 20892 USA. EM sissungt@mail.nih.gov OI Richardson, Tristan/0000-0001-7505-7843 NR 74 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 443 EP 456 DI 10.1007/978-1-4614-9135-4_22 D2 10.1007/978-1-4614-9135-4 PG 14 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300022 ER PT B AU Schrump, DS AF Schrump, David S. BE Figg, WD McLeod, HL TI Regional Drug Delivery for Inoperable Pulmonary Malignancies SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE Pulmonary metastases; Isolated lung perfusion; Inhalational drug delivery ID ISOLATED LUNG PERFUSION; TUMOR-NECROSIS-FACTOR; SOFT-TISSUE SARCOMAS; INTERLEUKIN-2 INHALATION-THERAPY; ISCHEMIA-REPERFUSION INJURY; I CLINICAL-TRIAL; PHASE-I; ARTERY PERFUSION; RAT MODEL; NATURAL INTERLEUKIN-2 AB Unresectable primary lung cancers and inoperable pulmonary metastases contribute significantly to cancer mortality throughout the world. Isolated lung perfusion and inhalation techniques are potential strategies to enhance delivery of chemotherapeutic as well as biologic agents to the lungs while minimizing systemic toxicities. This chapter reviews current efforts pertaining to regional drug delivery for inoperable pulmonary malignancies. C1 NCI, Thorac Surg Sect, Thorac & GI Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Schrump, DS (reprint author), NCI, Thorac Surg Sect, Thorac & GI Oncol Branch, Ctr Canc Res, Room 4-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM david_schrump@nih.gov NR 86 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 499 EP 518 DI 10.1007/978-1-4614-9135-4_25 D2 10.1007/978-1-4614-9135-4 PG 20 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300025 ER PT B AU Smart, D Camphausen, K AF Smart, DeeDee Camphausen, Kevin BE Figg, WD McLeod, HL TI Radiation and Altering Clinical Pharmacology SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE Ionizing radiation; Radiosensitizer; Radiation modifier; Clonogenic survival ID DEACETYLASE INHIBITOR MS-275; TUMOR-CELL RADIOSENSITIVITY; IONIZING-RADIATION; CANCER-CELLS; IN-VITRO; CONCURRENT CHEMOTHERAPY; MULTITARGET APPROACH; CLONOGENIC SURVIVAL; INDUCED APOPTOSIS; PELVIC RADIATION AB Ionizing radiation is a widely used therapeutic option in both curative and palliative cancer treatments, as well as in specialized benign conditions. Because the majority of cancer patients will receive radiation at some point in their treatment course, and because radiation is often given concurrently or sequentially with chemotherapy, it is critically important to understand the biology of how ionizing radiation affects tumor cells as well as normal tissue, how pharmacotherapy may alter the effectiveness of radiation, and how radiotherapy may augment standard pharmacologic interventions. C1 [Smart, DeeDee; Camphausen, Kevin] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bldg 10 CRC B2-SW3500,10 Ctr Dr, Bethesda, MD 20892 USA. EM camphauk@mail.nih.gov NR 69 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 541 EP 551 DI 10.1007/978-1-4614-9135-4_27 D2 10.1007/978-1-4614-9135-4 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300027 ER PT B AU Madan, RA Ferrara, TA Gulley, JL AF Madan, Ravi A. Ferrara, Theresa A. Gulley, James L. BE Figg, WD McLeod, HL TI Therapeutic Cancer Vaccines: An Emerging Approach to Cancer Treatment SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE Therapeutic vaccine; Immunotherapy; Combination therapy; Clinical trials ID CELL LUNG-CANCER; REFRACTORY PROSTATE-CANCER; ANTIGEN-PRESENTING CELLS; COLONY-STIMULATING FACTOR; BLP25 LIPOSOME VACCINE; HUMAN-TUMOR-MARKER; PHASE-III TRIAL; CARCINOEMBRYONIC ANTIGEN; COSTIMULATORY MOLECULES; COMBINATION THERAPY AB In the late 1990s, monoclonal antibodies and targeted molecular inhibitors revolutionized treatment options for patients with cancer. Since their development, outcomes for patients with chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and Her-2(+) breast cancer, among others, have significantly improved. While these anticancer agents continue to evolve, therapeutic cancer vaccines could be the next major therapeutic advance for cancer patients. Immunotherapy is already an accepted treatment for some cancers. BCG is a standard treatment for localized bladder cancer, while interferon alpha and interleukin-2 (IL-2) are used to treat melanoma and renal cell cancer. These nonspecific types of immunotherapy induce a broad immunologic response that may have an antitumor effect in a minority of patients. However, therapeutic cancer vaccines that can induce a specific, targeted antitumor immune response are currently in clinical development. Therapeutic cancer vaccines in metastatic prostate cancer have demonstrated overall survival advantages relative to placebo in multiple phase II and III trials, and there are compelling data for the clinical benefit of therapeutic cancer vaccines in other cancer types. Additional strategies are being investigated that employ combinations of vaccines and standard therapeutics, including hormonal therapy, radiation, and chemotherapy, in an effort to optimize the effects of vaccines. C1 [Madan, Ravi A.; Ferrara, Theresa A.; Gulley, James L.] NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bldg 10,Room 8B09,10 Ctr Dr, Bethesda, MD 20892 USA. EM gj50i@nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 115 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 553 EP 568 DI 10.1007/978-1-4614-9135-4_28 D2 10.1007/978-1-4614-9135-4 PG 16 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300028 ER PT B AU Kreitman, RJ AF Kreitman, Robert J. BE Figg, WD McLeod, HL TI Recombinant Immunotoxins SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE Monoclonal antibody; Fusion toxin; CD22; CD25; Diphtheria toxin; Pseudomonas exotoxin; Ricin; KDEL receptor; Fv; Chronic lymphocytic leukemia; Hairy cell leukemia; Adult T-cell leukemia; SS1P; CD19; Mesothelin; CD3 ID SINGLE-CHAIN IMMUNOTOXIN; HAIRY-CELL LEUKEMIA; PSEUDOMONAS EXOTOXIN-A; PHASE-I TRIAL; CONVECTION-ENHANCED DELIVERY; RECURRENT MALIGNANT GLIOMA; COLONY-STIMULATING FACTOR; CHRONIC LYMPHOCYTIC-LEUKEMIA; DIPHTHERIA-TOXIN RECEPTOR; ADVANCED SOLID TUMORS AB Recombinant immunotoxins contain a recombinant antibody and a protein toxin, capable of killing a cell after internalization and transport of the toxin to the cytosol. Growth factor fusion toxins, including the approved molecule denileukin diftitox, contain a growth factor such as interleukin-2 and truncated toxin. Recombinant immunotoxins furthest along in clinical development are BL22 (CAT-3888) and HA22 (CAT-8015 or moxetumomab pasudotox) targeting CD22 and LMB-2 targeting CD25. These agents have induced complete and partial responses in patients with chemoresistant hairy cell leukemia (HCL) and partial responses with other hematologic malignancies. Clinical development is continuing with these and other agents for different forms of cancer. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37 Room 5124b,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov NR 165 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 569 EP 584 DI 10.1007/978-1-4614-9135-4_29 D2 10.1007/978-1-4614-9135-4 PG 16 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300029 ER PT B AU Kummar, S Ivy, SP Harris, PJ AF Kummar, Shivaani Ivy, S. Percy Harris, Pamela Jo BE Figg, WD McLeod, HL TI Organ Dysfunction Trials: Background, Historical Barriers, Progress in Overcoming Barriers, and Suggestions for Future Trials SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE NCI organ dysfunction working group; Hepatic dysfunction; Renal dysfunction; Special population studies; Dose determination; Drug development ID IMPAIRED RENAL-FUNCTION; GLOMERULAR-FILTRATION-RATE; ADULT CANCER-PATIENTS; DRUG-METABOLIZING-ENZYMES; MULTIPLE-MYELOMA PATIENTS; PHASE-I; WORKING GROUP; CREATININE CLEARANCE; VARYING DEGREES; KIDNEY WEIGHT AB In the past, patients with cancer, who also have hepatic or renal dysfunction, have carried a triple burden. Not only have they suffered from cancer and organ dysfunction, but until recently, their oncologists have had inadequate information to tailor doses of drugs to their degree of organ dysfunction. In the past, phase 1 clinical trials in patients with organ dysfunction were either performed long after drug approval or not at all. This chapter provides background, a review of barriers to the conduct of clinical trials in this population, information about how these barriers have been largely overcome, and suggestions for conducting organ dysfunction trials in the future. C1 [Kummar, Shivaani] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Ivy, S. Percy; Harris, Pamela Jo] NCI, Invest Drug Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Ivy, SP (reprint author), NCI, Invest Drug Branch, Div Canc Treatment & Diag, 9606 Med Ctr Dr,MSC 9739, Bethesda, MD 20892 USA. EM ivyp@ctep.nci.nih.gov NR 53 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 673 EP 688 DI 10.1007/978-1-4614-9135-4_33 D2 10.1007/978-1-4614-9135-4 PG 16 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300033 ER PT B AU Kurdziel, KA Mena, E Adler, S Choyke, P AF Kurdziel, Karen A. Mena, Esther Adler, Stephen Choyke, Peter BE Figg, WD McLeod, HL TI Imaging in Drug Development SO HANDBOOK OF ANTICANCER PHARMACOKINETICS AND PHARMACODYNAMICS, 2ND EDITION SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE Dynamic radionuclide imaging; Early drug development; Positron Emission Tomography (PET) ID POSITRON-EMISSION-TOMOGRAPHY; PARTIAL-VOLUME CORRECTION; GASTROINTESTINAL STROMAL TUMORS; CEREBRAL GLUCOSE-UTILIZATION; STANDARDIZED UPTAKE VALUES; GRAPHICAL ANALYSIS METHOD; BRAIN TRANSFER CONSTANTS; ARTERIAL INPUT FUNCTION; TIME UPTAKE DATA; FDG-PET AB The challenge of drug development in oncology is to achieve optimum delivery of active drug to the tumor with minimal exposure to normal tissue. Newer, highly specific targeted drugs require careful evaluation of these parameters as these agents often leave alternative signaling pathways unblocked, thus providing a mechanism for resistance. Determining these characteristics early in the drug development cycle can reduce the human and monetary costs. Imaging provides a potential means of approximating the fate of a drug throughout the body (whole body imaging) and over time (dynamic imaging) in a noninvasive manner. There are many promising imaging technologies that could be applied to drug development. Among these, radionuclide tagging provides the most sensitive method. This chapter will focus on positron emission tomography (PET), as the most sensitive and quantitative among existing imaging modalities. C1 [Kurdziel, Karen A.; Mena, Esther; Choyke, Peter] CCR NCI, Mol Imaging Program, Bethesda, MD 20892 USA. [Adler, Stephen] Leidos Biomed Res Inc, Clin Res Directorate CMRP, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Kurdziel, KA (reprint author), CCR NCI, Mol Imaging Program, Bldg 10 Room B3B403, Bethesda, MD 20892 USA. EM kurdziek@mail.nih.gov; Esther.MenaGonzalez@nih.gov; sadler@mail.nih.gov; pchoyke@mail.nih.gov NR 88 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4614-9135-4; 978-1-4614-9134-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2014 BP 731 EP 746 DI 10.1007/978-1-4614-9135-4_36 D2 10.1007/978-1-4614-9135-4 PG 16 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BA6CE UT WOS:000337095300036 ER PT B AU Nicholson, BP Prasad, AS Chew, EY AF Nicholson, Benjamin P. Prasad, Ananda S. Chew, Emily Y. BE Preedy, VR TI Zinc Deficiency and the Eye SO HANDBOOK OF NUTRITION, DIET, AND THE EYE LA English DT Article; Book Chapter ID HIGH-DOSE SUPPLEMENTATION; ABNORMAL DARK-ADAPTATION; AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; NIGHT BLINDNESS; VITAMIN-C; HISTOCHEMICAL-LOCALIZATION; INFLAMMATORY CYTOKINES; OXIDATIVE STRESS; CLINICAL-TRIAL C1 [Nicholson, Benjamin P.; Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 USA. [Prasad, Ananda S.] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA. [Prasad, Ananda S.] Wayne State Univ, Barbara Ann Karmanos Canc Inst, Detroit, MI USA. RP Nicholson, BP (reprint author), NEI, NIH, Bethesda, MD 20892 USA. NR 50 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-404606-1; 978-0-12-401717-7 PY 2014 BP 371 EP 376 DI 10.1016/B978-0-12-401717-7.00037-X PG 6 WC Nutrition & Dietetics; Ophthalmology SC Nutrition & Dietetics; Ophthalmology GA BA6TH UT WOS:000337276300038 ER PT B AU Charles, BA AF Charles, Bashira A. BE Preedy, VR TI The Adenosine A(2a) Receptor and Diabetic Retinopathy SO HANDBOOK OF NUTRITION, DIET, AND THE EYE LA English DT Article; Book Chapter ID ENDOTHELIAL GROWTH-FACTOR; OXIDATIVE STRESS; CELLS; RETINA; COMPLICATIONS; EXPRESSION; MELLITUS; SUBTYPES; RISK; GENE C1 NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. RP Charles, BA (reprint author), NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. NR 69 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-404606-1; 978-0-12-401717-7 PY 2014 BP 525 EP 534 DI 10.1016/B978-0-12-401717-7.00053-8 PG 10 WC Nutrition & Dietetics; Ophthalmology SC Nutrition & Dietetics; Ophthalmology GA BA6TH UT WOS:000337276300054 ER PT S AU Lorsch, J AF Lorsch, Jon BE Lorsch, J TI METHODS IN ENZYMOLOGY Laboratory Methods in Enzymology: Protein Part C PREFACE SO LABORATORY METHODS IN ENZYMOLOGY: PROTEIN, PT C SE Methods in Enzymology LA English DT Editorial Material; Book Chapter C1 Natl Inst Gen Med Sci, Bethesda, MD 20892 USA. RP Lorsch, J (reprint author), Natl Inst Gen Med Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-420119-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2014 VL 541 BP XVII EP XVII PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA4CU UT WOS:000335365000001 ER PT S AU Sak, M Duric, N Littrup, P Bey-Knight, L Sherman, M Gierach, G Malyarenko, A AF Sak, Mark Duric, Neb Littrup, Peter Bey-Knight, Lisa Sherman, Mark Gierach, Gretchen Malyarenko, Antonina BE Bosch, JG Doyley, MM TI Comparison of sound speed measurements on two different ultrasound tomography devices SO MEDICAL IMAGING 2014: ULTRASONIC IMAGING AND TOMOGRAPHY SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Ultrasonic Imaging and Tomography CY FEB 18-20, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med DE Ultrasound tomography; Breast density; Sound speed; Hardware correlation ID BREAST-CANCER RISK; DENSITY; MODEL; PREDICTION; TISSUE; WOMEN AB Ultrasound tomography (UST) employs sound waves to produce three-dimensional images of breast tissue and precisely measures the attenuation of sound speed secondary to breast tissue composition. High breast density is a strong breast cancer risk factor and sound speed is directly proportional to breast density. UST provides a quantitative measure of breast density based on three-dimensional imaging without compression, thereby overcoming the shortcomings of many other imaging modalities. The quantitative nature of the UST breast density measures are tied to an external standard, so sound speed measurement in breast tissue should be independent of specific hardware. The work presented here compares breast sound speed measurement obtained with two different UST devices. The Computerized Ultrasound Risk Evaluation (CURE) system located at the Karmanos Cancer Institute in Detroit, Michigan was recently replaced with the SoftVue ultrasound tomographic device. Ongoing clinical trials have used images generated from both sets of hardware, so maintaining consistency in sound speed measurements is important. During an overlap period when both systems were in the same exam room, a total of 12 patients had one or both of their breasts imaged on both systems on the same day. There were 22 sound speed scans analyzed from each system and the average breast sound speeds were compared. Images were either reconstructed using saved raw data (for both CURE and SoftVue) or were created during the image acquisition (saved in DICOM format for SoftVue scans only). The sound speed measurements from each system were strongly and positively correlated with each other. The average difference in sound speed between the two sets of data was on the order of 1-2 m/s and this result was not statistically significant. The only sets of images that showed a statistical difference were the DICOM images created during the SoftVue scan compared to the SoftVue images reconstructed from the raw data. However, the discrepancy between the sound speed values could be easily handled by uniformly increasing the DICOM sound speed by approximately 0.5 m/s. These results suggest that there is no fundamental difference in sound speed measurement for the two systems and support combining data generated with these instruments in future studies. C1 [Sak, Mark; Duric, Neb; Littrup, Peter; Bey-Knight, Lisa; Malyarenko, Antonina] Wayne State Univ, Karmanos Canc Inst, 4100 John R St, Detroit, MI 48201 USA. [Duric, Neb; Littrup, Peter] Delphinus Med Technol, Plymouth, MI 48170 USA. [Sherman, Mark] Breast & Gynecol Canc Res, Natl Canc Inst, Canc Prevent Div, Bethesda, MD 20892 USA. [Gierach, Gretchen] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Sak, M (reprint author), Wayne State Univ, Karmanos Canc Inst, 4100 John R St, Detroit, MI 48201 USA. RI Gierach, Gretchen/E-1817-2016 OI Gierach, Gretchen/0000-0002-0165-5522 FU National Institutes of Health; National Cancer Institute FX This work was supported ( in part) by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 15 TC 0 Z9 0 U1 0 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9833-5 J9 PROC SPIE PY 2014 VL 9040 AR UNSP 90400S DI 10.1117/12.2043113 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA9FB UT WOS:000339329900024 PM 25309102 ER PT B AU Castilho, RM Gutkind, JS AF Castilho, Rogerio M. Gutkind, J. Silvio BE Burtness, B Golemis, EA TI The Wnt/beta-catenin Signaling Circuitry in Head and Neck Cancer SO MOLECULAR DETERMINANTS OF HEAD AND NECK CANCER SE Current Cancer Research LA English DT Article; Book Chapter DE Wnt; Squamous carcinoma; Oral cancer; HPV; beta-catenin; Epigenetics; Signal transduction; Oncogenome; Cancer stem cells ID SQUAMOUS-CELL CARCINOMA; FAMILIAL ADENOMATOUS POLYPOSIS; LASER-CAPTURE MICRODISSECTION; HAIR FOLLICLE MORPHOGENESIS; PREDICTS INCREASED RISK; BETA-CATENIN; STEM-CELLS; WNT PATHWAY; BREAST-CANCER; EPIGENETIC INACTIVATION AB We have recently gained an unprecedented knowledge of the most frequent genetic alterations in head and neck squamous cell carcinoma (HNSCC). We have also learned that the aberrant function of multiple signaling networks contributes to HNSCC initiation and progression, including the persistent activation of the PI3K/Akt/mTOR, NF kappa B, and STAT3 signaling pathways and decreased antiproliferative responses to Notch and TGF-beta. Emerging evidence suggests that many regulatory components of the Wnt signaling pathway are also dysfunctional in HNSCC, leading to increased nuclear beta-catenin levels. This includes increased expression of Wnt family members and their coreceptor, Frizzled, loss of heterozygosity of the adenomatosis polyposis coli (APC) tumor suppressor gene, and epigenetic events leading to decreased expression of APC and the Wnt antagonists the secreted Frizzled-related proteins (SFRPs), Wnt inhibitory factors (WIFs) and Dickkopf family members (DKKs), primarily by promoter hypermethylation. Wnt/beta-catenin controls cell fate decisions in normal epithelial stem cells, but persistent beta-catenin signaling contributes to increased growth, metastatic potential and resistance to chemotherapy in HNSCC and their tumor-initiating cells. While the role of Wnt/beta-catenin in HNSCC is not as well defined as in other cancers, the development of small molecule inhibitors of the Wnt/beta-catenin pathway for other cancer types may soon afford novel targeted options for the treatment of HNSCC lesions displaying aberrant Wnt signaling. C1 [Castilho, Rogerio M.] Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Lab Epithelial Biol, Ann Arbor, MI 48109 USA. [Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Castilho, RM (reprint author), Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Lab Epithelial Biol, Ann Arbor, MI 48109 USA. EM rcastilh@umich.edu NR 97 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-8815-6; 978-1-4614-8814-9 J9 CURR CANCER RES PY 2014 BP 199 EP 214 DI 10.1007/978-1-4614-8815-6_10 D2 10.1007/978-1-4614-8815-6 PG 16 WC Oncology SC Oncology GA BA7YK UT WOS:000337901600010 ER PT S AU Needle, D Waugh, DS AF Needle, Danielle Waugh, David S. BE Giannone, RJ Dykstra, AB TI Rescuing Aggregation-Prone Proteins in Escherichia coli with a Dual His(6)-MBP Tag SO PROTEIN AFFINITY TAGS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Maltose-binding protein; MBP; Fusion protein; Solubility enhancer; TEV protease; Tobacco etch virus protease; Hexahistidine tag; His-tag; His(6)-MBP; Gateway (R) cloning; Recombinational cloning ID SOLUBILITY AB Insolubility of recombinant proteins in Escherichia coli is a major impediment to their production for structural and functional studies. One way around this problem is to fuse an aggregation-prone protein to a highly soluble partner. E. coli maltose-binding protein (MBP) is widely recognized as a premier solubilizing agent. In this chapter, we describe how to construct dual His(6)-MBP-tagged fusion proteins by Gateway (R) recombinational cloning and how to predict their yield and solubility. We also describe a simple and rapid procedure to test the ability of a His(6)-MBP fusion protein to bind to Ni-NTA resin and to be digested by tobacco etch virus (TEV) protease, along with a method to assess the solubility of the target protein after it has been separated from His(6)-MBP. C1 [Needle, Danielle; Waugh, David S.] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Needle, D (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21701 USA. FU Intramural NIH HHS NR 9 TC 4 Z9 5 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1034-2; 978-1-4939-1033-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1177 BP 81 EP 94 DI 10.1007/978-1-4939-1034-2_7 D2 10.1007/978-1-4939-1034-2 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA8ET UT WOS:000338028700008 PM 24943316 ER PT S AU Locatelli-Hoops, SC Yeliseev, AA AF Locatelli-Hoops, Silvia C. Yeliseev, Alexei A. BE Giannone, RJ Dykstra, AB TI Use of Tandem Affinity Chromatography for Purification of Cannabinoid Receptor CB2 SO PROTEIN AFFINITY TAGS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE His-tag; Strep-tag; Dual affinity tags; Membrane protein; CB2 receptor; StrepTactin; Ni-NTA ID ETCH VIRUS PROTEASE; EXPRESSION; POLYPEPTIDES; BINDING; TAGS AB Tandem affinity purification has been increasingly applied to isolation of recombinant proteins. It relies on two consecutive chromatographic steps that take advantage of the affinity tags placed at opposing ends of the target protein. This allows for efficient removal of contaminating proteins, including products of proteolytic degradation of the fusion that lack either N- or C-terminal tags. Here, we describe the use of two small affinity tags, a poly-histidine tag and a Strep-tag for expression and purification of the human cannabinoid receptor CB 2, an integral membrane G protein-coupled receptor. C1 [Locatelli-Hoops, Silvia C.; Yeliseev, Alexei A.] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Locatelli-Hoops, SC (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 AA999999] NR 13 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1034-2; 978-1-4939-1033-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1177 BP 107 EP 120 DI 10.1007/978-1-4939-1034-2_9 D2 10.1007/978-1-4939-1034-2 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA8ET UT WOS:000338028700010 PM 24943318 ER PT S AU Savage, SA AF Savage, Sharon A. BE Calado, RT TI Human Telomeres and Telomere Biology Disorders SO TELOMERES IN HEALTH AND DISEASE SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID BONE-MARROW FAILURE; STEM-CELL TRANSPLANTATION; LINKED DYSKERATOSIS-CONGENITA; HOYERAAL-HREIDARSSON-SYNDROME; SPORADIC PULMONARY-FIBROSIS; SEVERE APLASTIC-ANEMIA; REVERSE-TRANSCRIPTASE; CEREBELLAR HYPOPLASIA; COMBINED IMMUNODEFICIENCY; PROGRESSIVE PANCYTOPENIA AB Telomeres consist of long nucleotide repeats and a protein complex at chromosome ends essential for chromosome stability. Telomeres shorten with each cell division and thus are markers of cellular age. Dyskeratosis congenita (DC) is a cancer-prone inherited bone marrow failure syndrome caused by germ-line mutations in key telomere biology genes that result in extremely short telomeres. The triad of nail dysplasia, abnormal skin pigmentation, and oral leukoplakia is diagnostic of DC but highly variable. Patients with DC may also have but numerous other medical problems, including pulmonary fibrosis, liver abnormalities, avascular necrosis of the hips, and stenosis of the esophagus, lacrimal ducts, and/or urethra. All modes of inheritance have been reported in DC and de novo mutations are common. Broad phenotypic heterogeneity occurs within DC. Clinically severe variants of DC are Hoyeraal-Hreidarsson syndrome and Revesz syndrome. Coats plus syndrome joined the spectrum of DC with the discovery that it is caused by mutations in a telomere-capping gene. Less clinically severe variants, such as subsets of apparently isolated aplastic anemia or pulmonary fibrosis, have also been recognized. These patients may not have the DC-associated mucocutaneous triad or complicated medical features, but they do have the same underlying genetic etiology. This has led to the use of the descriptive term telomere biology disorder (TBD). This chapter will review the connection between telomere biology and human disease through the examples of DC and its related TBDs. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Savage, SA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU Intramural NIH HHS NR 118 TC 15 Z9 15 U1 5 U2 17 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-397898-1 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2014 VL 125 BP 41 EP 66 DI 10.1016/B978-0-12-397898-1.00002-5 PG 26 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA9CV UT WOS:000339223600003 PM 24993697 ER PT S AU Bodelon, C Savage, SA Gadalla, SM AF Bodelon, Clara Savage, Sharon A. Gadalla, Shahinaz M. BE Calado, RT TI Telomeres in Molecular Epidemiology Studies SO TELOMERES IN HEALTH AND DISEASE SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID DYSKERATOSIS-CONGENITA; PROSTATE-CANCER; CARDIOVASCULAR-DISEASE; ULCERATIVE-COLITIS; CIGARETTE-SMOKING; LENGTH DYNAMICS; SOUTHERN BLOTS; BUCCAL CELLS; IN-SITU; RISK AB Telomeres are long nucleotide repeats and protein complexes at the ends of chromosomes that are essential for maintaining chromosomal stability. They shorten with each cell division, and therefore, telomere length is a marker for cellular aging and senescence. Epidemiological research of telomeres investigates the role that these genetic structures have in disease risk and mortality in human populations. This chapter provides an overview of the current telomere epidemiology research and discusses approaches taken in these investigations. We also highlight important methodological considerations that may affect data interpretation. C1 [Bodelon, Clara; Savage, Sharon A.; Gadalla, Shahinaz M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Bodelon, C (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU Intramural NIH HHS NR 88 TC 7 Z9 8 U1 4 U2 13 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-397898-1 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2014 VL 125 BP 113 EP 131 DI 10.1016/B978-0-12-397898-1.00005-0 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA9CV UT WOS:000339223600006 PM 24993700 ER PT S AU Pobezinskaya, YL Liu, ZG Choksi, S AF Pobezinskaya, Yelena L. Liu, Zhenggang Choksi, Swati BE Bayry, J TI Dissecting DR3 Signaling SO TNF SUPERFAMILY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Death receptor 3; MAP kinases; NF-kB; Proliferation; T cells; Immunoprecipitation; CFSE ID DOMAIN-CONTAINING RECEPTOR; TNF-LIKE LIGAND; NECROSIS-FACTOR RECEPTOR; T-CELL; TL1A; EXPRESSION; APOPTOSIS; DISEASE; TRADD AB Receptor signaling can be evaluated in multiple ways, including analysis of phosphorylation of downstream molecules and analysis of proteins that are recruited to the receptor upon ligand binding. Majority of studies on the mechanism of DR3 signaling were performed using overexpression systems that can often lead to artifacts. In this chapter we describe how to analyze DR3 downstream events with most attention being paid to endogenous immunoprecipitation. C1 [Pobezinskaya, Yelena L.; Liu, Zhenggang; Choksi, Swati] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. RP Pobezinskaya, YL (reprint author), NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0669-7; 978-1-4939-0668-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1155 BP 15 EP 22 DI 10.1007/978-1-4939-0669-7_2 D2 10.1007/978-1-4939-0669-7 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA8TO UT WOS:000338665000003 PM 24788169 ER PT J AU Farci, P Bukh, J AF Farci, Patrizia Bukh, Jens BE Thomas, HC Lok, ASF Locarnini, SA Zuckerman, AJ TI Animal models of hepatitis C virus infection SO VIRAL HEPATITIS, 4TH EDITION LA English DT Article; Book Chapter ID NON-B-HEPATITIS; HYPERVARIABLE REGION 1; NON-A-HEPATITIS; IN-VIVO; CELL-CULTURE; LONG-TERM; HUMAN LIVER; CDNA-CLONE; EXPERIMENTAL TRANSMISSION; NEUTRALIZING ANTIBODIES AB The chimpanzee model has played a major role both before and after the discovery of hepatitis C virus (HCV), the etiologic agent of non-A, non-B hepatitis (NANBH). Chimpanzees were essential to prove that NANBH was indeed an infectious disease caused by a transmissible agent, and they provided an in vivo system for the biological amplification of the putative virus to obtain sufficient material for attempts at identification. It was from a chronically infected chimpanzee that a large amount of plasma was obtained for the molecular cloning of the HCV genome. The chimpanzee model has played a critical role not only in the initial discovery but also in the post-HCV era. Studies in chimpanzees were instrumental to investigate the host immune response elicited by HCV and to determine the natural history of hepatitis C. Finally, chimpanzees remain the only animal model to study the immunogenicity and efficacy of vaccine candidates against HCV. In this chapter, we review the role that nonhuman primate models have played before and after the discovery of the etiologic agent of NANBH. Furthermore, we discuss the utility of small-animal models that have been developed over the past 10 years for studies of HCV. C1 [Farci, Patrizia] NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Bukh, Jens] Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis Program CO HEP C, Hvidovre, Denmark. [Bukh, Jens] Copenhagen Univ Hosp, Clin Res Ctr, Hvidovre, Denmark. [Bukh, Jens] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark. RP Farci, P (reprint author), NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NR 104 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-67295-2 PY 2014 BP 280 EP 294 PG 15 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA BA5VL UT WOS:000337034100020 ER PT J AU Laskin, WB Fetsch, JF Miettinen, M AF Laskin, William B. Fetsch, John F. Miettinen, Markku TI Myxoinflammatory Fibroblastic Sarcoma A Clinicopathologic Analysis of 104 Cases, With Emphasis on Predictors of Outcome SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE myxoinflammatory fibroblastic sarcoma; acral myxoinflammatory fibroblastic sarcoma; myxofibrosarcoma; viral inclusion body-like nucleolus; immunohistochemistry ID HEMOSIDEROTIC FIBROLIPOMATOUS TUMOR; FIBROHISTIOCYTIC LIPOMATOUS LESION; HYALINIZING ANGIECTATIC TUMOR; INFLAMMATORY MYXOHYALINE TUMOR; DENDRITIC CELL TUMORS; CYTOGENETIC ANALYSIS; SOFT PARTS; MARKER; GRADE; PODOPLANIN AB In this study, we examine the clinicopathologic features of 104 cases of myxoinflammatory fibroblastic sarcoma (MIFS), a low-grade, inflammatory fibromyxoid tumor with a predilection to distal extremity soft tissue, and attempt to identify factors predictive of aggressive behavior. The study cohort consisted of 49 male and 55 female patients ranging in age from 17 to 83 (mean, 42; median, 39) years. The tumor arose primarily on the dorsal aspect of the distal extremities as a solitary and usually painless mass. Tumors ranged in size from 0.5 to 15 (mean, 3.2; median; 2.4) cm. Microscopically, tumors consisted of variably cellular and inflamed fibromyxoid tissue growing as a lobulated mass or as multiple nodules within subcutaneous tissue or along tendinofascial planes. Tumor cells ranged from plump spindled to more epithelioid cells with enlarged, vesicular nuclei. Characteristic of the process was a strikingly bizarre cell with an inclusion body-like nucleolus (85% of cases) and/or a smudgy hyperchromatic nucleus (51%) present in all but 7 cases. The mitotic rate per 50 high-power field ranged from 0 to 13 (mean, 2,9; median, 2) mitoses. Twenty-two tumors demonstrated 1 or more of the following atypical features: (1) foci with complex sarcomalike vasculature; (2) hypercellular areas; and (3) increased mitotic activity or atypical mitotic figures. Immunohistochemically, tumor cells demonstrated immunoreactivity for vimentin (100%), D2-40 (86%), CD34 (50%), keratin(s) (33%), CD68 (27%), actin( s) (26%), desmin (9%), S-100 protein (7%), and epithelial membrane antigen (6%). Thirty of 59 patients (51%) with followup data suffered (at least) 1 local recurrence, and 1 patient developed metastatic disease after multiple local recurrences. Completeness of initial surgical excision was the only clinicopathologic parameter that statistically correlated with a lower incidence of recurrence (P=0.004). Histologically atypical MIFS recurred more often than conventional tumors (67% vs. 47%), but the difference was not statistically significant (P=0.35). Our study shows that histologic features often associated with more aggressive sarcomas do not substantially impact the morbidity of MIFS, and complete surgical excision provides the best chance for disease-free survival. C1 [Laskin, William B.] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. [Fetsch, John F.] Joint Pathol Ctr, Dept Soft Tissue Pathol, Silver Spring, MD USA. [Miettinen, Markku] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Laskin, WB (reprint author), NW Mem Hosp, Dept Pathol, Feinberg Pavil 7-325,251 East Huron St, Chicago, IL 60611 USA. EM wbl769@northwestern.edu NR 45 TC 12 Z9 14 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2014 VL 38 IS 1 BP 1 EP 12 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA AL2VF UT WOS:000338983000001 PM 24121178 ER PT J AU Miettinen, M McCue, PA Sarlomo-Rikala, M Rys, J Czapiewski, P Wazny, K Langfort, R Waloszczyk, P Biernat, W Lasota, J Wang, ZF AF Miettinen, Markku McCue, Peter A. Sarlomo-Rikala, Maarit Rys, Janusz Czapiewski, Piotr Wazny, Krzysztof Langfort, Renata Waloszczyk, Piotr Biernat, Wojciech Lasota, Jerzy Wang, Zengfeng TI GATA3: A Multispecific But Potentially Useful Marker in Surgical Pathology A Systematic Analysis of 2500 Epithelial and Nonepithelial Tumors SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE GATA3; breast cancer; urothelial cancer; choriocarcinoma; endodermal sinus tumor; chromophobe renal carcinoma; mesothelioma; immunohistochemistry ID PLACENTAL S100 S100P; UROTHELIAL CARCINOMA; CELL-DIFFERENTIATION; INTERCALATED CELLS; RENAL ONCOCYTOMA; EXPRESSION; BREAST; CANCER; MORPHOGENESIS; REGULATOR AB GATA3 is a transcription factor important in the differentiation of breast epithelia, urothelia, and subsets of T lymphocytes. It has been suggested to be useful in the evaluation of carcinomas of mammary or urothelial origin or metastatic carcinomas, but its distribution in normal and neoplastic tissues is incompletely mapped. In this study, we examined normal developing and adult tissues and 2040 epithelial and 460 mesenchymal or neuroectodermal neoplasms for GATA3 expression to explore its diagnostic value in surgical pathology, using monoclonal antibody (clone L50-823) and Leica Bond automated immunohistochemistry. GATA3 was expressed in trophoblast, fetal and adult epidermis, adult mammary and some salivary gland and sweat gland ductal epithelia, urothelia, distal nephron in developing and adult tissues, some prostatic basal cells, and subsets of T lymphocytes. It was expressed stronger in fetal than in adult mesothelia and was absent in respiratory and gastrointestinal epithelia. In epithelial neoplasms, GATA3 was expressed in >90% of primary and metastatic ductal and lobular carcinomas of the breast, urothelial, and cutaneous basal cell carcinomas and trophoblastic and endodermal sinus tumors. In metastatic breast carcinomas, it was more sensitive than GCDFP. Among squamous cell carcinomas, the expression was highest in the skin (81%) and lower in cervical (33%), laryngeal (16%), and pulmonary tu-mors (12%). Common positivity was found in skin adnexal tumors (100%), mesothelioma (58%), salivary gland (43%), and pancreatic (37%) ductal carcinomas, whereas frequency of expression in adenocarcinomas of lung, stomach, colon, endometrium, ovary, and prostate was <10%. Chromophobe renal cell carcinoma was a unique renal tumor with frequent positivity (51%), whereas oncocytomas were positive in 17% of cases but other types only rarely. Among mesenchymal and neuroectodermal tumors, paragangliomas were usually positive, which sets these tumors apart from epithelial neuroendocrine tumors. Mesenchymal tumors were only sporadically positive, except epithelia of biphasic synovial sarcomas. GATA3 is a useful marker in the characterization of not only mammary and urothelial but also renal and germ cell tumors, mesotheliomas, and paragangliomas. The multiple specificities of GATA3 should be taken into account when using this marker to detect metastatic mammary or urothelial carcinomas. C1 [Miettinen, Markku; Lasota, Jerzy; Wang, Zengfeng] NCI, Lab Surg Pathol, Bethesda, MD 20892 USA. [McCue, Peter A.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Cell Biol & Anat, Philadelphia, PA 19107 USA. [McCue, Peter A.] Univ Hosp, Philadelphia, PA USA. [Sarlomo-Rikala, Maarit] Helsinki Univ Hosp, Dept Pathol, Haartman Inst, Helsinki, Finland. [Sarlomo-Rikala, Maarit] Helsinki Univ Hosp, HusLab, Helsinki, Finland. [Rys, Janusz] Maria Sklodowska Curie Mem Inst Oncol, Dept Tumor Pathol, Ctr Oncol, Krakow Branch, Krakow, Poland. [Czapiewski, Piotr; Wazny, Krzysztof; Biernat, Wojciech] Med Univ Gdansk, Dept Pathomorphol, Gdansk, Poland. [Langfort, Renata] Natl TB & Lung Dis Res Inst, Dept Pathol, Warsaw, Poland. [Waloszczyk, Piotr] Zdunomed, Independent Lab Pathol, Szczecin, Poland. RP Miettinen, M (reprint author), NCI, Lab Surg Pathol, 9000 Rockville Pike,Bldg 10,Rm 2B50, Bethesda, MD 20892 USA. EM miettinenmm@mail.nih.gov RI Waloszczyk, Piotr/A-8399-2015 FU NCI FX Conflicts of Interest and Source of Funding: Supported as a part of NCI's intramural research program. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 31 TC 90 Z9 96 U1 0 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2014 VL 38 IS 1 BP 13 EP 22 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA AL2VF UT WOS:000338983000002 PM 24145643 ER PT S AU Tinkle, S McNeil, SE Muhlebach, S Bawa, R Borchard, G Barenholz, Y Tamarkin, L Desai, N AF Tinkle, Sally McNeil, Scott E. Muehlebach, Stefan Bawa, Raj Borchard, Gerrit Barenholz, Yechezkel (Chezy) Tamarkin, Lawrence Desai, Neil GP Annals New York Acad Sci TI Nanomedicines: addressing the scientific and regulatory gap SO ANNALS REPORTS SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE nanomedicine; nanosimilars; nanopharmaceuticals; regulation; patents; nanotechnology; non-biologic complex drug (NBCD); follow-on biologics; biosimilars; immunogenicity; pharmacokinetics; pharmacodynamics; Abbreviated New Drug Application (ANDA); bioequivalence ID PEGYLATED LIPOSOMAL DOXORUBICIN; TUMOR-NECROSIS-FACTOR; COMPLEX-DRUGS NBCD; COLLOIDAL GOLD; PRODUCTS; PHARMACOKINETICS; ACTIVATION; EFFICIENT; DELIVERY AB Nanomedicine is the application of nanotechnology to the discipline of medicine: the use of nanoscale materials for the diagnosis, monitoring, control, prevention, and treatment of disease. Nanomedicine holds tremendous promise to revolutionize medicine across disciplines and specialties, but this promise has yet to be fully realized. Beyond the typical complications associated with drug development, the fundamentally different and novel physical and chemical properties of some nanomaterials compared to materials on a larger scale (i.e., their bulk counterparts) can create a unique set of opportunities as well as safety concerns, which have only begun to be explored. As the research community continues to investigate nanomedicines, their efficacy, and the associated safety issues, it is critical to work to close the scientific and regulatory gaps to assure that nanomedicine drives the next generation of biomedical innovation. C1 [Tinkle, Sally] IDA Sci & Technol Policy Inst, Washington, DC 20006 USA. [McNeil, Scott E.] Frederick Natl Lab Canc Res, Nanotechnol Characterizat Lab, Frederick, MD USA. [Muehlebach, Stefan] Vifor Pharma Ltd, Glattbrugg, Switzerland. [Muehlebach, Stefan] Univ Basel, Basel, Switzerland. [Bawa, Raj] Bawa Biotech LLC, Ashburn, VA USA. [Bawa, Raj] Rensselaer Polytech Inst, Troy, NY USA. [Borchard, Gerrit] Univ Geneva, Sch Pharmaceut Sci Geneva Lausanne, Geneva, Switzerland. [Barenholz, Yechezkel (Chezy)] Hebrew Univ Jerusalem, Hadassah Med Sch, IL-91010 Jerusalem, Israel. [Tamarkin, Lawrence] CytImmune, Rockville, MD USA. [Desai, Neil] Abraxis Biosci Celgene Corp, Los Angeles, CA USA. RP Tinkle, S (reprint author), IDA Sci & Technol Policy Inst, Washington, DC 20006 USA. EM annals@nyas.org RI Nanotechnology Characterization Lab, NCL/K-8454-2012 NR 46 TC 50 Z9 51 U1 7 U2 33 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2014 VL 1313 BP 35 EP 56 DI 10.1111/nyas.12403 PG 22 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BA8GQ UT WOS:000338100700003 PM 24673240 ER PT J AU Kim, HY Kim, HR Kang, MG Trang, NTD Baek, HJ Moon, JD Shin, JH Suh, SP Ryang, DW Kook, H Shin, MG AF Kim, Hwan-Young Kim, Hye-Ran Kang, Min-Gu Nguyen Thi Dai Trang Baek, Hee-Jo Moon, Jae-Dong Shin, Jong-Hee Suh, Soon-Pal Ryang, Dong-Wook Kook, Hoon Shin, Myung-Geun TI Profiling of Biomarkers for the Exposure of Polycyclic Aromatic Hydrocarbons: Lamin-A/C Isoform 3, Poly[ADP-ribose] Polymerase 1, and Mitochondria Copy Number Are Identified as Universal Biomarkers SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID BLOOD-CELL DNA; ENVIRONMENTAL EXPOSURE; 1-HYDROXYPYRENE; ADDUCTS; URINE; CYTOTOXICITY; ELIMINATION; ACTIVATION; CHEMICALS; SMOKING AB This study investigated the profiling of polycyclic aromatic hydrocarbon- (PAH-) induced genotoxicity in cell lines and zebrafish. Each type of cells displayed different proportionality of apoptosis. Mitochondrial DNA (mtDNA) copy number was dramatically elevated after 5-day treatment of fluoranthene and pyrene. The notable deregulated proteins for PAHs exposure were displayed as follows: lamin-A/C isoform3 and annexin A1 for benzopyrene; lamin-A/C isoform3 and DNA topoisomerase 2-alpha for pentacene; poly[ADP-ribose] polymerase 1 (PARP-1) for fluoranthene; and talin-1 and DNA topoisomerase 2-alpha for pyrene. Among them, lamin-A/C isoform 3 and PARP-1 were further confirmed using mRNA and protein expression study. Obvious morphological abnormalities including curved backbone and cardiomegaly in zebrafish were observed in the 54 hpf with more than 400 nM of benzopyrene. In conclusion, the change of mitochondrial genome (increased mtDNA copy number) was closely associated with PAH exposure in cell lines and mesenchymal stem cells. Lamin-A/C isoform 3, talin-1, and annexin A1 were identified as universal biomarkers for PAHs exposure. Zebrafish, specifically at embryo stage, showed suitable in vivo model for monitoring PAHs exposure to hematopoietic tissue and other organs. C1 [Kim, Hwan-Young; Kang, Min-Gu; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook; Shin, Myung-Geun] Chonnam Natl Univ, Sch Med, Dept Lab Med, Hwasun Gun 519809, Jeollanam Do, South Korea. [Kim, Hwan-Young; Kang, Min-Gu; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook; Shin, Myung-Geun] Chonnam Natl Univ, Hwasun Hosp, Hwasun Gun 519809, Jeollanam Do, South Korea. [Kim, Hwan-Young; Kim, Hye-Ran; Nguyen Thi Dai Trang; Shin, Myung-Geun] Chonnam Natl Univ, Sch Med, Brain Korea Plus Project 21, Kwangju, South Korea. [Kim, Hye-Ran] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Baek, Hee-Jo; Moon, Jae-Dong; Kook, Hoon; Shin, Myung-Geun] Chonnam Natl Univ, Hwasun Hosp, Environm Hlth Ctr Childhood Leukemia & Canc, Hwasun, South Korea. RP Shin, MG (reprint author), Chonnam Natl Univ, Sch Med, Dept Lab Med, 160 Ilsimri, Hwasun Gun 519809, Jeollanam Do, South Korea. EM mgshin@chonnam.ac.kr OI Kang, Min-Gu/0000-0003-4946-8512 FU National Research Foundation of Korea (NRF) - Korea government (MEST) [2011-0015304]; Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology (MEST) [2011-0030034]; National R&D Program for Cancer Control Ministry of Health & Welfare, Republic of Korea [2013-1320070]; Ministry of Health & Welfare, Republic of Korea [2013-1320070] FX The authors are thankful to the National Research Foundation of Korea (NRF) and grants funded by the Korea government (MEST) (no. 2011-0015304); the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST) (no. 2011-0030034); and a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (no. 2013-1320070). NR 38 TC 1 Z9 1 U1 1 U2 8 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 605135 DI 10.1155/2014/605135 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AL5QR UT WOS:000339188800001 ER PT J AU Zhou, JM Xiang, Y Yoshimura, T Chen, KQ Gong, WH Huang, J Zhou, Y Yao, XH Bian, XW Wang, JM AF Zhou, Jiamin Xiang, Yi Yoshimura, Teizo Chen, Keqiang Gong, Wanghua Huang, Jian Zhou, Ye Yao, Xiaohong Bian, Xiuwu Wang, Ji Ming TI The Role of Chemoattractant Receptors in Shaping the Tumor Microenvironment SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID SQUAMOUS-CELL CARCINOMA; REGULATORY T-CELLS; LYMPH-NODE METASTASIS; MESENCHYMAL STEM-CELLS; BREAST-CANCER CELLS; ENDOTHELIAL PROGENITOR CELLS; PANCREATIC DUCTAL ADENOCARCINOMA; NF-KAPPA-B; HUMAN HEPATOCELLULAR-CARCINOMA; SMALL-MOLECULE ANTAGONISTS AB Chemoattractant receptors are a family of seven transmembrane G protein coupled receptors (GPCRs) initially found to mediate the chemotaxis and activation of immune cells. During the past decades, the functions of these GPCRs have been discovered to not only regulate leukocyte trafficking and promote immune responses, but also play important roles in homeostasis, development, angiogenesis, and tumor progression. Accumulating evidence indicates that chemoattractant GPCRs and their ligands promote the progression of malignant tumors based on their capacity to orchestrate the infiltration of the tumor microenvironment by immune cells, endothelial cells, fibroblasts, and mesenchymal cells. This facilitates the interaction of tumor cells with host cells, tumor cells with tumor cells, and host cells with host cells to provide a basis for the expansion of established tumors and development of distant metastasis. In addition, many malignant tumors of the nonhematopoietic origin express multiple chemoattractant GPCRs that increase the invasiveness and metastasis of tumor cells. Therefore, GPCRs and their ligands constitute targets for the development of novel antitumor therapeutics. C1 [Zhou, Jiamin; Xiang, Yi; Yoshimura, Teizo; Chen, Keqiang; Wang, Ji Ming] Natl Canc Inst, Ctr Canc Res, Lab Mol Immunoregulat Canc & Inflammat Program, Frederick, MD 21702 USA. [Xiang, Yi] Fudan Univ, Zhongshan Hosp, Endoscop Ctr, Shanghai 200032, Peoples R China. [Xiang, Yi] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Pulm Med, Shanghai 200025, Peoples R China. [Gong, Wanghua] Leidos Biomed Res Inc, Basic Res Program, Frederick, MD 21702 USA. [Huang, Jian; Yao, Xiaohong; Bian, Xiuwu] Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing 400038, Peoples R China. [Huang, Jian; Yao, Xiaohong; Bian, Xiuwu] Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing 400038, Peoples R China. [Zhou, Ye] Fudan Univ, Ctr Canc, Dept Gastr Canc & Soft Tissue Surg, Shanghai 200032, Peoples R China. RP Wang, JM (reprint author), Natl Canc Inst, Ctr Canc Res, Lab Mol Immunoregulat Canc & Inflammat Program, Frederick, MD 21702 USA. EM wangji@mail.nih.gov RI Bian, Xiu-wu/D-4736-2017 OI Bian, Xiu-wu/0000-0003-4383-0197 FU Federal funds from the National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the NCI, NIH; China Scholarship Council, National Natural Science Foundation of China [81101566]; Scientific Funds of Shanghai Government [11DZ2280400, 12QA1400600, XYQ2011017, 11411950500]; National Natural Science Foundation of China [81101771]; Shanghai Municipal Commission "Exchange Scholars" FX This project has been funded in part by Federal funds from the National Cancer Institute, National Institutes of Health, under Contract no. HHSN261200800001E. The research was also supported in part by the Intramural Research Program of the NCI, NIH. Jiamin Zhou is funded in part by China Scholarship Council, National Natural Science Foundation of China (no. 81101566), and Scientific Funds of Shanghai Government (11DZ2280400, 12QA1400600, XYQ2011017, and 11411950500). Yi Xiang is funded in part by the National Natural Science Foundation of China (no. 81101771) and Shanghai Municipal Commission "Exchange Scholars." The authors thank Dr. Joost J Oppenheim for critical review of the paper and Ms. Cheryl Lamb and Ms. Sharon Livingstone for secretarial assistance. NR 509 TC 6 Z9 6 U1 3 U2 24 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 751392 DI 10.1155/2014/751392 PG 33 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AL6MQ UT WOS:000339247200001 ER PT B AU Ferguson, SM Kaundinya, US AF Ferguson, Steven M. Kaundinya, Uma S. BE Shimasaki, C TI Licensing the Technology: Biotechnology Commercialization Strategies Using University and Federal Labs SO BIOTECHNOLOGY ENTREPRENEURSHIP: STARTING, MANAGING, AND LEADING BIOTECH COMPANIES LA English DT Article; Book Chapter C1 [Ferguson, Steven M.] NIH, Off Technol Transfer, Rockville, MD 20849 USA. [Kaundinya, Uma S.] Aavishkar Innovat Inc, Bedford, MA USA. RP Ferguson, SM (reprint author), NIH, Off Technol Transfer, Rockville, MD 20849 USA. NR 17 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-404747-1; 978-0-12-404730-3 PY 2014 BP 185 EP 206 DI 10.1016/B978-0-12-404730-3.00014-2 PG 22 WC Business; Management SC Business & Economics GA BA6TR UT WOS:000337279500016 ER PT J AU Bruno, RD Smith, GH AF Bruno, Robert D. Smith, Gilbert H. TI A potential mechanism for extracellular matrix induction of breast cancer cell normality SO BREAST CANCER RESEARCH LA English DT Editorial Material ID MAMMARY MICROENVIRONMENT; KNOCKOUT MICE; BIGLYCAN; PHENOTYPE; GLAND AB Extracellular matrix proteins from embryonic mesenchyme have a normalizing effect on cancer cells in vitro and slow tumor growth in vivo. This concept is suggestive of a new method for controlling the growth and spread of existing cancer cells in situ and indicates the possibility that extracellular proteins and/or embryonic mesenchymal fibroblasts may represent a fertile subject for study of new anti-cancer treatments. C1 [Bruno, Robert D.] Old Dominion Univ, Coll Hlth Sci, Sch Med Diagnost & Translat Sci, Norfolk, VA 23529 USA. [Smith, Gilbert H.] NCI, Mammary Stem Cell Biol Sect, CCBB, Ctr Canc Res, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NCI, Mammary Stem Cell Biol Sect, CCBB, Ctr Canc Res, Bethesda, MD 20892 USA. EM smithg@mail.nih.gov OI Bruno, Robert/0000-0003-3329-9478 NR 15 TC 1 Z9 1 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 1 AR 302 DI 10.1186/bcr3617 PG 2 WC Oncology SC Oncology GA AL2VI UT WOS:000338983300002 PM 25927296 ER PT J AU Meerzaman, DM Yan, CH Chen, QR Edmonson, MN Schaefer, CF Clifford, RJ Dunn, BK Dong, L Finney, RP Cultraro, CM Hu, Y Yang, ZH Nguyen, CV Kelley, JM Cai, S Zhang, HG Zhang, JH Wilson, R Messmer, L Chung, YH Kim, JA Park, NH Lyu, MS Song, IH Komatsoulis, G Buetow, KH AF Meerzaman, Daoud M. Yan, Chunhua Chen, Qing-Rong Edmonson, Michael N. Schaefer, Carl F. Clifford, Robert J. Dunn, Barbara K. Dong, Li Finney, Richard P. Cultraro, Constance M. Hu, Ying Yang, Zhihui Nguyen, Cu V. Kelley, Jenny M. Cai, Shuang Zhang, Hongen Zhang, Jinghui Wilson, Rebecca Messmer, Lauren Chung, Young-Hwa Kim, Jeong A. Park, Neung Hwa Lyu, Myung-Soo Song, Il Han Komatsoulis, George Buetow, Kenneth H. TI Genome-wide Transcriptional Sequencing Identifies Novel Mutations in Metabolic Genes in Human Hepatocellular Carcinoma SO CANCER GENOMICS & PROTEOMICS LA English DT Article DE Hepatocellular carcinoma (HCC); RNA-seq; gene expression; mutation ID INSULIN-RECEPTOR SUBSTRATE-1; FATTY LIVER-DISEASE; UNITED-STATES; RISK-FACTORS; PATHOGENESIS; CANCER; PHOSPHORYLATION; OVEREXPRESSION; CARCINOGENESIS; ACTIVATION AB We report on next-generation transcriptome sequencing results of three human hepatocellular carcinoma tumor/tumor-adjacent pairs. This analysis robustly examined similar to 12,000 genes for both expression differences and molecular alterations. We observed 4,513 and 1,182 genes demonstrating 2-fold or greater increase or decrease in expression relative to their normal, respectively. Network analysis of expression data identified the Aurora B signaling, FOXM1 transcription factor network and Wnt signaling pathways pairs being altered in HCC. We validated as differential gene expression findings in a large data set containing of 434 liver normal/tumor sample pairs. In addition to known driver mutations in TP53 and CTNNB1, our mutation analysis identified non-synonymous mutations in genes implicated in metabolic diseases, i.e. diabetes and obesity: IRS1, HMGCS1, ATP8B1, PRMT6 and CLU, suggesting a common molecular etiology for HCC of alternative pathogenic origin. C1 [Meerzaman, Daoud M.; Yan, Chunhua; Chen, Qing-Rong; Edmonson, Michael N.; Schaefer, Carl F.; Finney, Richard P.; Hu, Ying; Nguyen, Cu V.; Zhang, Jinghui; Komatsoulis, George; Buetow, Kenneth H.] NCI, Ctr Bioinformat & Informat Technol, Rockville, MD USA. [Meerzaman, Daoud M.; Clifford, Robert J.; Dong, Li; Cultraro, Constance M.; Yang, Zhihui; Kelley, Jenny M.; Cai, Shuang; Zhang, Hongen; Wilson, Rebecca; Messmer, Lauren; Buetow, Kenneth H.] NCI, Lab Populat Genet, Bethesda, MD 20892 USA. [Dunn, Barbara K.] NCI, Basic Prevent Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Zhang, Jinghui] St Jude Childrens Res Hosp, Dept Biotechnol Computat Biol, Memphis, TN 38105 USA. [Chung, Young-Hwa; Kim, Jeong A.] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Internal Med, Seoul, South Korea. [Park, Neung Hwa; Lyu, Myung-Soo] Univ Ulsan, Coll Med, Ulsan Univ Hosp, Dept Internal Med, Ulsan 680749, South Korea. [Song, Il Han] Dankook Univ, Coll Med, Dept Internal Med, Cheonan, South Korea. RP Meerzaman, DM (reprint author), Ctr Biomed Informat & Informat Technol, 9609 Med Ctr Dr,1W466, Rockville, MD 20850 USA. EM meerzamd@mail.nih.gov NR 43 TC 6 Z9 6 U1 0 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 1109-6535 EI 1790-6245 J9 CANCER GENOM PROTEOM JI Cancer Genomics Proteomics PD JAN-FEB PY 2014 VL 11 IS 1 BP 1 EP 12 PG 12 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA AL8MS UT WOS:000339393900001 PM 24633315 ER PT B AU Del Fiol, G Yu, H Cimino, JJ AF Del Fiol, Guilherme Yu, Hong Cimino, James J. BE Greenes, RA TI lnfobuttons and Point of Care Access to Knowledge SO CLINICAL DECISION SUPPORT: THE ROAD TO BROAD ADOPTION, 2ND EDITION LA English DT Article; Book Chapter ID CLINICIAN INFORMATION NEEDS; WORLD-WIDE-WEB; CONTINUOUS SPEECH RECOGNITION; RANDOMIZED CONTROLLED-TRIAL; QUESTION ANSWERING SYSTEM; PATIENT-CARE; CLASSIFICATION MODELS; RETRIEVAL SYSTEMS; DECISION-SUPPORT; ONLINE EVIDENCE C1 [Del Fiol, Guilherme] Univ Utah, Salt Lake City, UT 84112 USA. [Yu, Hong] Univ Massachusetts, Sch Med, Dept Comp Sci, Dept Quantitat Hlth Sci, Worcester, MA USA. [Cimino, James J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA. RP Del Fiol, G (reprint author), Univ Utah, Salt Lake City, UT 84112 USA. OI Del Fiol, Guilherme/0000-0001-9954-6799 NR 108 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-800542-2; 978-0-12-398476-0 PY 2014 BP 515 EP 549 PG 35 WC Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA BA6TO UT WOS:000337278900021 ER PT B AU Col, N Correa-de-Araujo, R AF Col, Nananda Correa-de-Araujo, Rosaly BE Greenes, RA TI Consumers and Clinical Decision Support SO CLINICAL DECISION SUPPORT: THE ROAD TO BROAD ADOPTION, 2ND EDITION LA English DT Article; Book Chapter ID AFRICAN-AMERICAN ADOLESCENTS; RANDOMIZED CONTROLLED-TRIAL; HEALTH-INFORMATION; PATIENT PARTICIPATION; AIDS-PREVENTION; SEXUAL-BEHAVIOR; NATIONAL ACTION; BREAST-CANCER; FOCUS GROUPS; ORDER ENTRY C1 [Col, Nananda] Univ New England, Coll Osteopath Med, Biddeford, ME 04005 USA. [Correa-de-Araujo, Rosaly] NIA, Div Geriatr & Clin Gerontol, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Col, N (reprint author), Univ New England, Coll Osteopath Med, Biddeford, ME 04005 USA. NR 115 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-800542-2; 978-0-12-398476-0 PY 2014 BP 741 EP 769 PG 29 WC Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA BA6TO UT WOS:000337278900029 ER PT S AU Pelletier, M Billingham, LK Ramaswamy, M Siegel, RM AF Pelletier, Martin Billingham, Leah K. Ramaswamy, Madhu Siegel, Richard M. BE Galluzzi, L Kroemer, G TI Extracellular Flux Analysis to Monitor Glycolytic Rates and Mitochondrial Oxygen Consumption SO CONCEPTUAL BACKGROUND AND BIOENERGETIC/MITOCHONDRIAL ASPECTS OF ONCOMETABOLISM SE Methods in Enzymology LA English DT Review; Book Chapter ID T-CELL-ACTIVATION; MACROPHAGE-MEDIATED INFLAMMATION; TARGETING CANCER METABOLISM; ENERGY-METABOLISM; IN-VIVO; DIABETIC ATHEROSCLEROSIS; RHEUMATOID-ARTHRITIS; OXIDATIVE-METABOLISM; RADIOLABELED ACETATE; GLUCOSE-METABOLISM AB Evidence accumulating over the past decade has linked alterations in bioenergetic metabolism to the pathogenesis of several diseases, including inflammatory conditions and cancer. However, the mutual relationship between the effector functions and the metabolism of immune cells has begun to emerge only recently. Similar to malignant cells, both innate and adaptive immune cells undergo a metabolic reprogramming that is required for effector functions, de facto underlying the elicitation of a robust immune response. These changes allow immune cells not only to rapidly respond to pathogens or (pre)malignant cells but also to adapt to changing microenvironmental conditions. Targeting the metabolic alterations of malignant cells has been the subject of an intense wave of investigation, resulting in the identification of promising therapeutic strategies. Since the inflammatory milieu and the tumor microenvironment are similar, the metabolism of immune cells and its regulation has recently come under renewed interest as a target for immunotherapy. Here, we describe different tools and techniques to study the bioenergetic metabolism of cultured cells, using immune cells as a model. Our methodological approach relies on an extracellular flux analyzer, an instrument that enables the real-time measurement of the two central pathways used by living cells to generate adenosine triphosphate: glycolysis and oxidative phosphorylation. This instrument and similar technological innovations have transformed the study of cellular metabolism, unveiling its profound impact on various immunologic and oncological disorders. C1 [Pelletier, Martin; Billingham, Leah K.; Ramaswamy, Madhu; Siegel, Richard M.] Natl Inst Arthrit Musculoskeletal & Skin Dis NIAM, Autoimmun Branch, Immunoregulat Sect, NIH, Bethesda, MD 20892 USA. RP Siegel, RM (reprint author), Natl Inst Arthrit Musculoskeletal & Skin Dis NIAM, Autoimmun Branch, Immunoregulat Sect, NIH, Bethesda, MD 20892 USA. EM siegelr@mail.nih.gov NR 86 TC 8 Z9 8 U1 2 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-416618-9 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2014 VL 542 BP 125 EP 149 DI 10.1016/B978-0-12-416618-9.00007-8 PG 25 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA6ZJ UT WOS:000337330600008 PM 24862264 ER PT S AU Kang, JG Wang, PY Hwang, PM AF Kang, Ju-Gyeong Wang, Ping-yuan Hwang, Paul M. BE Galluzzi, L Kroemer, G TI Cell-Based Measurements of Mitochondrial Function in Human Subjects SO CONCEPTUAL BACKGROUND AND BIOENERGETIC/MITOCHONDRIAL ASPECTS OF ONCOMETABOLISM SE Methods in Enzymology LA English DT Review; Book Chapter ID CANCER METABOLISM AB There is growing evidence in the basic science field that aberrant metabolism plays an important role in tumorigenesis. Therefore, it is imperative to perform investigations in human subjects to determine (1) whether the metabolic observations made in model systems are applicable to humans; and (2) if indeed applicable, whether the metabolic alterations are clinically significant for cancer development. As an initial step, here we describe methods for measuring the mitochondrial metabolism of blood lymphocytes and skeletal muscle myoblasts that can be obtained from human subjects. C1 [Kang, Ju-Gyeong; Wang, Ping-yuan; Hwang, Paul M.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. RP Hwang, PM (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA. EM hwangp@mail.nih.gov FU Intramural NIH HHS [ZIA HL005101-11] NR 10 TC 1 Z9 1 U1 2 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-416618-9 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2014 VL 542 BP 209 EP 221 DI 10.1016/B978-0-12-416618-9.00011-X PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA6ZJ UT WOS:000337330600012 PM 24862268 ER PT J AU Brownstein, CA Beggs, AH Homer, N Merriman, B Yu, TW Flannery, KC DeChene, ET Towne, MC Savage, SK Price, EN Holm, IA Luquette, LJ Lyon, E Majzoub, J Neupert, P McCallie, D Szolovits, P Willard, HF Mendelsohn, NJ Temme, R Finkel, RS Yum, SW Medne, L Sunyaev, SR Adzhubey, I Cassa, CA de Bakker, PIW Duzkale, H Dworzynski, P Fairbrother, W Francioli, L Funke, BH Giovanni, MA Handsaker, RE Lage, K Lebo, MS Lek, M Leshchiner, I MacArthur, DG McLaughlin, HM Murray, MF Pers, TH Polak, PP Raychaudhuri, S Rehm, HL Soemedi, R Stitziel, NO Vestecka, S Supper, J Gugenmus, C Klocke, B Hahn, A Schubach, M Menzel, M Biskup, S Freisinger, P Deng, M Braun, M Perner, S Smith, RJH Andorf, JL Huang, J Ryckman, K Sheffield, VC Stone, EM Bair, T Black-Ziegelbein, EA Braun, TA Darbro, B DeLuca, AP Kolbe, DL Scheetz, TE Shearer, AE Sompallae, R Wang, K Bassuk, AG Edens, E Mathews, K Moore, SA Shchelochkov, OA Trapane, P Bossler, A Campbell, CA Heusel, JW Kwitek, A Maga, T Panzer, K Wassink, T Van Daele, D Azaiez, H Booth, K Meyer, N Segal, MM Williams, MS Tromp, G White, P Corsmeier, D Fitzgerald-Butt, S Herman, G Lamb-Thrush, D McBride, KL Newsom, D Pierson, CR Rakowsky, AT Maver, A Lovrecic, L Palandacic, A Peterlin, B Torkamani, A Wedell, A Huss, M Alexeyenko, A Lindvall, JM Magnusson, M Nilsson, D Stranneheim, H Taylan, F Gilissen, C Hoischen, A van Bon, B Yntema, H Nelen, M Zhang, WD Sager, J Zhang, L Blair, K Kural, D Cariaso, M Lennon, GG Javed, A Agrawal, S Ng, PC Sandhu, KS Krishna, S Veeramachaneni, V Isakov, O Halperin, E Friedman, E Shomron, N Glusman, G Roach, JC Caballero, J Cox, HC Mauldin, D Ament, SA Rowen, L Richards, DR San Lucas, FA Gonzalez-Garay, ML Caskey, CT Bai, Y Huang, Y Fang, F Zhang, Y Wang, ZY Barrera, J Garcia-Lobo, JM Gonzalez-Lamuno, D Llorca, J Rodriguez, MC Varela, I Reese, MG De la Vega, FM Kiruluta, E Cargill, M Hart, RK Sorenson, JM Lyon, GJ Stevenson, DA Bray, BE Moore, BM Eilbeck, K Yandell, M Zhao, HY Hou, L Chen, XW Yan, XT Chen, MJ Li, C Yang, C Gunel, M Li, PN Kong, Y Alexander, AC Albertyn, ZI Boycott, KM Bulman, DE Gordon, PMK Innes, AM Knoppers, BM Majewski, J Marshall, CR Parboosingh, JS Sawyer, SL Samuels, ME Schwartzentruber, J Kohane, IS Margulies, DM AF Brownstein, Catherine A. Beggs, Alan H. Homer, Nils Merriman, Barry Yu, Timothy W. Flannery, Katherine C. DeChene, Elizabeth T. Towne, Meghan C. Savage, Sarah K. Price, Emily N. Holm, Ingrid A. Luquette, Lovelace J. Lyon, Elaine Majzoub, Joseph Neupert, Peter McCallie, David, Jr. Szolovits, Peter Willard, Huntington F. Mendelsohn, Nancy J. Temme, Renee Finkel, Richard S. Yum, Sabrina W. Medne, Livija Sunyaev, Shamil R. Adzhubey, Ivan Cassa, Christopher A. de Bakker, Paul I. W. Duzkale, Hatice Dworzynski, Piotr Fairbrother, William Francioli, Laurent Funke, Birgit H. Giovanni, Monica A. Handsaker, Robert E. Lage, Kasper Lebo, Matthew S. Lek, Monkol Leshchiner, Ignaty MacArthur, Daniel G. McLaughlin, Heather M. Murray, Michael F. Pers, Tune H. Polak, Paz P. Raychaudhuri, Soumya Rehm, Heidi L. Soemedi, Rachel Stitziel, Nathan O. Vestecka, Sara Supper, Jochen Gugenmus, Claudia Klocke, Bernward Hahn, Alexander Schubach, Max Menzel, Mortiz Biskup, Saskia Freisinger, Peter Deng, Mario Braun, Martin Perner, Sven Smith, Richard J. H. Andorf, Janeen L. Huang, Jian Ryckman, Kelli Sheffield, Val C. Stone, Edwin M. Bair, Thomas Black-Ziegelbein, E. Ann Braun, Terry A. Darbro, Benjamin DeLuca, Adam P. Kolbe, Diana L. Scheetz, Todd E. Shearer, Aiden E. Sompallae, Rama Wang, Kai Bassuk, Alexander G. Edens, Erik Mathews, Katherine Moore, Steven A. Shchelochkov, Oleg A. Trapane, Pamela Bossler, Aaron Campbell, Colleen A. Heusel, Jonathan W. Kwitek, Anne Maga, Tara Panzer, Karin Wassink, Thomas Van Daele, Douglas Azaiez, Hela Booth, Kevin Meyer, Nic Segal, Michael M. Williams, Marc S. Tromp, Gerard White, Peter Corsmeier, Donald Fitzgerald-Butt, Sara Herman, Gail Lamb-Thrush, Devon McBride, Kim L. Newsom, David Pierson, Christopher R. Rakowsky, Alexander T. Maver, Ales Lovrecic, Luca Palandacic, Anja Peterlin, Borut Torkamani, Ali Wedell, Anna Huss, Mikael Alexeyenko, Andrey Lindvall, Jessica M. Magnusson, Mans Nilsson, Daniel Stranneheim, Henrik Taylan, Fulya Gilissen, Christian Hoischen, Alexander van Bon, Bregje Yntema, Helger Nelen, Marcel Zhang, Weidong Sager, Jason Zhang, Lu Blair, Kathryn Kural, Deniz Cariaso, Michael Lennon, Greg G. Javed, Asif Agrawal, Saloni Ng, Pauline C. Sandhu, Komal S. Krishna, Shuba Veeramachaneni, Vamsi Isakov, Ofer Halperin, Eran Friedman, Eitan Shomron, Noam Glusman, Gustavo Roach, Jared C. Caballero, Juan Cox, Hannah C. Mauldin, Denise Ament, Seth A. Rowen, Lee Richards, Daniel R. San Lucas, F. Anthony Gonzalez-Garay, Manuel L. Caskey, C. Thomas Bai, Yu Huang, Ying Fang, Fang Zhang, Yan Wang, Zhengyuan Barrera, Jorge Garcia-Lobo, Juan M. Gonzalez-Lamuno, Domingo Llorca, Javier Rodriguez, Maria C. Varela, Ignacio Reese, Martin G. De la Vega, Francisco M. Kiruluta, Edward Cargill, Michele Hart, Reece K. Sorenson, Jon M. Lyon, Gholson J. Stevenson, David A. Bray, Bruce E. Moore, Barry M. Eilbeck, Karen Yandell, Mark Zhao, Hongyu Hou, Lin Chen, Xiaowei Yan, Xiting Chen, Mengjie Li, Cong Yang, Can Gunel, Murat Li, Peining Kong, Yong Alexander, Austin C. Albertyn, Zayed I. Boycott, Kym M. Bulman, Dennis E. Gordon, Paul M. K. Innes, A. Micheil Knoppers, Bartha M. Majewski, Jacek Marshall, Christian R. Parboosingh, Jillian S. Sawyer, Sarah L. Samuels, Mark E. Schwartzentruber, Jeremy Kohane, Isaac S. Margulies, David M. TI An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge SO GENOME BIOLOGY LA English DT Article ID BURROWS-WHEELER TRANSFORM; DE-NOVO MUTATIONS; WHOLE-GENOME; GENETIC-VARIATION; CENTRONUCLEAR MYOPATHY; READ ALIGNMENT; TITIN GENE; EXOME; DISEASE; VARIANTS AB Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups. C1 [Brownstein, Catherine A.; Beggs, Alan H.; Yu, Timothy W.; DeChene, Elizabeth T.; Towne, Meghan C.; Savage, Sarah K.; Price, Emily N.; Holm, Ingrid A.; Margulies, David M.] Res Connect, Div Genet & Genom, Boston, MA 02127 USA. [Brownstein, Catherine A.; Beggs, Alan H.; Yu, Timothy W.; DeChene, Elizabeth T.; Towne, Meghan C.; Savage, Sarah K.; Price, Emily N.; Holm, Ingrid A.; Margulies, David M.] Harvard Univ, Sch Med, Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. [Homer, Nils] Claritas Genom, Boston, MA USA. [Merriman, Barry] Life Technol, Carlsbad, CA USA. [Flannery, Katherine C.; Luquette, Lovelace J.; Kohane, Isaac S.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Lyon, Elaine] Univ Utah, Sch Med, ARUP Labs, Salt Lake City, UT USA. [Majzoub, Joseph] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [Neupert, Peter] Microsoft Corp, Microsoft Hlth Solut Grp, Seattle, WA USA. [McCallie, David, Jr.] Cerner Corp, Med Informat, Kansas City, MO USA. [Szolovits, Peter] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Willard, Huntington F.] Duke Univ, Duke Inst Genome Sci & Policy, Durham, NC USA. [Mendelsohn, Nancy J.; Temme, Renee] Childrens Hosp & Clin Minnesota, Dept Med Genet, Minneapolis, MN USA. [Finkel, Richard S.] Nemours Childrens Hosp, Div Neurol, Orlando, FL USA. [Yum, Sabrina W.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Yum, Sabrina W.] Univ Penn, Perelmen Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Medne, Livija] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Sunyaev, Shamil R.; Adzhubey, Ivan; Cassa, Christopher A.; de Bakker, Paul I. W.; Giovanni, Monica A.; Leshchiner, Ignaty; Murray, Michael F.; Polak, Paz P.; Raychaudhuri, Soumya; Stitziel, Nathan O.; Vestecka, Sara] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [de Bakker, Paul I. W.; Francioli, Laurent] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Duzkale, Hatice; Funke, Birgit H.; Lebo, Matthew S.; Leshchiner, Ignaty; McLaughlin, Heather M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Mol Med,Partners Healthcare Ctr Personalized, Boston, MA 02115 USA. [Dworzynski, Piotr] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Fairbrother, William; Soemedi, Rachel] Brown Univ, Ctr Computat Mol Biol, Providence, RI 02912 USA. [Handsaker, Robert E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Lage, Kasper] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Boston, MA USA. [Lek, Monkol; MacArthur, Daniel G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Analyt & Translat Genet Unit, Boston, MA USA. [Pers, Tune H.] Childrens Hosp Boston, Div Endocrinol, Boston, MA USA. [Pers, Tune H.] Childrens Hosp Boston, Ctr Basic & Translat Obes Res, Boston, MA USA. [Supper, Jochen; Gugenmus, Claudia; Klocke, Bernward; Hahn, Alexander] Genomatix Software GmbH, Munich, Germany. [Supper, Jochen; Schubach, Max; Menzel, Mortiz; Biskup, Saskia; Freisinger, Peter] CeGaT GmbH, Tubingen, Germany. [Freisinger, Peter] Childrens Hosp Reutlingen, Reutlingen, Germany. [Deng, Mario; Braun, Martin; Perner, Sven] Univ Hosp Bonn, Inst Pathol, Dept Prostate Canc Res, Bonn, Germany. [Smith, Richard J. H.; Andorf, Janeen L.; Sheffield, Val C.; Stone, Edwin M.; Bair, Thomas; Black-Ziegelbein, E. Ann; Darbro, Benjamin; DeLuca, Adam P.; Kolbe, Diana L.; Scheetz, Todd E.; Shearer, Aiden E.; Sompallae, Rama; Bassuk, Alexander G.; Edens, Erik; Mathews, Katherine; Moore, Steven A.; Shchelochkov, Oleg A.; Trapane, Pamela; Bossler, Aaron; Campbell, Colleen A.; Heusel, Jonathan W.; Kwitek, Anne; Maga, Tara; Panzer, Karin; Wassink, Thomas; Van Daele, Douglas; Azaiez, Hela; Booth, Kevin; Meyer, Nic] Univ Iowa, Carver Coll Med, Iowa Inst Human Genet, Iowa City, IA USA. [Huang, Jian] Univ Iowa, Coll Liberal Arts & Sci, Iowa Inst Human Genet, Iowa City, IA USA. [Ryckman, Kelli] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa Inst Human Genet, Iowa City, IA USA. [Sheffield, Val C.; Stone, Edwin M.] Univ Iowa, Howard Hughes Med Inst, Iowa City, IA 52242 USA. [Braun, Terry A.] Univ Iowa, Coll Engn, Iowa Inst Human Genet, Iowa City, IA USA. [Wang, Kai] Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa Inst Human Genet, Iowa City, IA USA. [Segal, Michael M.] SimulConsult, Chestnut Hill, MA USA. [Williams, Marc S.; Tromp, Gerard] Geisinger Hlth Syst, Danville, PA USA. [White, Peter; Corsmeier, Donald; Fitzgerald-Butt, Sara; Herman, Gail; Lamb-Thrush, Devon; McBride, Kim L.; Newsom, David; Pierson, Christopher R.; Rakowsky, Alexander T.] Ohio State Univ, Dept Pediat, Nationwide Childrens Hosp, Columbus, OH 43210 USA. [Maver, Ales; Lovrecic, Luca; Palandacic, Anja; Peterlin, Borut] Univ Med Ctr Ljubljana, Dept Obstet & Gynecol, Clin Inst Med Genet, Ljubljana, Slovenia. [Torkamani, Ali] Scripps Res Inst, Scripps Translat Sci Inst, La Jolla, CA 92037 USA. [Wedell, Anna; Magnusson, Mans; Nilsson, Daniel; Stranneheim, Henrik; Taylan, Fulya] Karolinska Inst, Dept Mol Med & Surg, Sci Life Lab, Stockholm, Sweden. [Wedell, Anna; Magnusson, Mans; Stranneheim, Henrik] Karolinska Univ Hosp, Ctr Inherited Metab Disorders, Stockholm, Sweden. [Wedell, Anna; Magnusson, Mans; Nilsson, Daniel; Stranneheim, Henrik; Taylan, Fulya] Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. [Huss, Mikael] Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-10691 Stockholm, Sweden. [Alexeyenko, Andrey] Royal Inst Technol, Sch Biotechnol, Sci Life Lab, Stockholm, Sweden. [Lindvall, Jessica M.] Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden. [Nilsson, Daniel] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Gilissen, Christian; Hoischen, Alexander; van Bon, Bregje; Yntema, Helger; Nelen, Marcel] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Zhang, Weidong; Sager, Jason] Sanofi, Cambridge, MA USA. [Zhang, Lu; Blair, Kathryn; Kural, Deniz] Seven Bridges Genom Inc, Cambridge, MA USA. [Cariaso, Michael; Lennon, Greg G.] River Rd Bio, Potomac, MD USA. [Javed, Asif; Agrawal, Saloni; Ng, Pauline C.] ASTAR, Computat & Math Biol Genome Inst Singapore, Singapore, Singapore. [Sandhu, Komal S.; Krishna, Shuba; Veeramachaneni, Vamsi] Strand Life Sci, Bangalore, Karnataka, India. [Isakov, Ofer; Halperin, Eran; Friedman, Eitan; Shomron, Noam] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Glusman, Gustavo; Roach, Jared C.; Caballero, Juan; Cox, Hannah C.; Mauldin, Denise; Ament, Seth A.; Rowen, Lee] Inst Syst Biol, Seattle, WA USA. [Richards, Daniel R.] Ingenu Syst, Redwood City, CA USA. [San Lucas, F. Anthony] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Univ Texas Grad Sch Biomed Sci, Houston, TX 77030 USA. [Gonzalez-Garay, Manuel L.] UTHealth, Brown Fdn Inst Mol Med, Ctr Mol Imaging, Div Next Generat Sequencing, Houston, TX USA. [Caskey, C. Thomas] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Bai, Yu; Huang, Ying] Regeneron Pharmaceut Inc, Tarrytown, NY USA. [Fang, Fang] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Zhang, Yan; Wang, Zhengyuan] NHLBI, NIH, Bethesda, MD 20892 USA. [Barrera, Jorge; Garcia-Lobo, Juan M.; Rodriguez, Maria C.; Varela, Ignacio] Inst Biomed & Biotecnol Cantabria IBBTEC, Santander, Cantabria, Spain. [Barrera, Jorge; Garcia-Lobo, Juan M.; Rodriguez, Maria C.; Varela, Ignacio] CSIC, Santander, Cantabria, Spain. [Barrera, Jorge; Garcia-Lobo, Juan M.; Llorca, Javier; Rodriguez, Maria C.; Varela, Ignacio] Univ Cantabria, E-39005 Santander, Cantabria, Spain. [Barrera, Jorge; Garcia-Lobo, Juan M.; Rodriguez, Maria C.; Varela, Ignacio] SODERCAN, Santander, Cantabria, Spain. [Garcia-Lobo, Juan M.] Univ Cantabria, Dept Biol Mol, E-39005 Santander, Cantabria, Spain. [Gonzalez-Lamuno, Domingo] Univ Cantabria, Dept Ciencias Med & Quirurg, Div Pediat, E-39005 Santander, Cantabria, Spain. [Gonzalez-Lamuno, Domingo] Hosp Univ Marques Valdecilla, IFIMAV Inst Formac & Invest Marques Valdecilla, Santander, Cantabria, Spain. [Llorca, Javier] CIBER Epidemiol & Salud Publ CIBERESP, Santander, Cantabria, Spain. [Llorca, Javier] Inst Formac & Invest Marques Valdecilla IFIMAV, Santander, Cantabria, Spain. [Reese, Martin G.; De la Vega, Francisco M.; Kiruluta, Edward] Omicia Inc, Emeryville, CA USA. [De la Vega, Francisco M.] Real Time Genom Inc, San Bruno, CA USA. [Cargill, Michele; Hart, Reece K.; Sorenson, Jon M.] InVitae, San Francisco, CA 94107 USA. [Lyon, Gholson J.] Stanley Inst Cognit Genom, Cold Spring Harbor Lab, New York, NY USA. [Lyon, Gholson J.] Utah Fdn Biomed Res, Salt Lake City, UT USA. [Stevenson, David A.] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA. [Bray, Bruce E.] Univ Utah, Sch Med, Div Cardiol, Salt Lake City, UT USA. [Bray, Bruce E.] Univ Utah, Sch Med, Dept Biomed Informat, Salt Lake City, UT USA. [Moore, Barry M.; Yandell, Mark] Univ Utah, Sch Med, Dept Human Genet, Eccles Inst Human Genet, Salt Lake City, UT 84132 USA. [Moore, Barry M.; Eilbeck, Karen] Univ Utah, Sch Med, Salt Lake City, UT USA. [Zhao, Hongyu; Hou, Lin; Yang, Can] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA. [Chen, Xiaowei; Chen, Mengjie; Li, Cong] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT USA. [Yan, Xiting] Yale Univ, Keck Lab, Biostat Resource, New Haven, CT USA. [Gunel, Murat] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Gunel, Murat] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Li, Peining] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Kong, Yong] Yale Univ, WM Keck Fdn Biotechnol Resource Lab, Dept Mol Biophys & Biochem, New Haven, CT USA. [Alexander, Austin C.] Pearlgen Inc, Durham, NC USA. [Albertyn, Zayed I.] Novocraft Technol Sdn Bhd, Selangor, Malaysia. [Boycott, Kym M.; Bulman, Dennis E.; Sawyer, Sarah L.] Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada. [Gordon, Paul M. K.; Innes, A. Micheil; Parboosingh, Jillian S.] Univ Calgary, ACHRI, Calgary, AB, Canada. [Innes, A. Micheil; Parboosingh, Jillian S.] Univ Calgary, Dept Med Genet, Calgary, AB, Canada. [Knoppers, Bartha M.] McGill Univ, Ctr Genom & Policy, Montreal, PQ, Canada. [Majewski, Jacek; Schwartzentruber, Jeremy] McGill Univ, Montreal, PQ, Canada. [Majewski, Jacek; Schwartzentruber, Jeremy] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Marshall, Christian R.] Univ Toronto, Hosp Sick Children, Ctr Appl Genom, McLaughlin Ctr, Toronto, ON M5G 1X8, Canada. [Samuels, Mark E.] Univ Montreal, CHU Ste Justine, Ctr Rech, Dept Med, Montreal, PQ, Canada. RP Beggs, AH (reprint author), Res Connect, Div Genet & Genom, Boston, MA 02127 USA. EM beggs@enders.tch.harvard.edu; isaac_kohane@harvard.edu; David.Margulies@childrens.harvard.edu RI van Bon, Bregje/Q-2445-2015; Alexeyenko, Andrey/F-1924-2016; Varela, Ignacio/G-1699-2016; Fang, Fang/G-7679-2016; Gilissen, Christian/E-5246-2012; innes, allan micheil/A-9955-2017; Garcia Lobo, Juan/K-2727-2014; Rodriguez, Maria-Cruz/K-6533-2014; Llorca, Javier/F-7371-2011; YANG, Can/J-8790-2014; de Bakker, Paul/B-8730-2009; McBride, Kim/A-5879-2008; White, Peter/E-4301-2011; peterlin, borut/C-6086-2011; Nilsson, Daniel/B-8365-2009; Hoischen, Alexander/D-1282-2013; Yntema, H.G./L-4771-2015; Nelen, Marcel/L-4542-2015; OI Alexeyenko, Andrey/0000-0001-8812-6481; Varela, Ignacio/0000-0002-0969-506X; Gilissen, Christian/0000-0003-1693-9699; Blair, Kate/0000-0003-0766-0952; Lindvall, Jessica/0000-0002-5042-8481; Glusman, Gustavo/0000-0001-8060-5955; Bradley, Maria/0000-0001-7192-5041; Garcia Lobo, Juan/0000-0002-9187-0671; Rodriguez, Maria-Cruz/0000-0001-6778-1663; Llorca, Javier/0000-0001-8569-861X; YANG, Can/0000-0003-3368-3082; de Bakker, Paul/0000-0001-7735-7858; McBride, Kim/0000-0002-8407-8942; White, Peter/0000-0002-5218-5903; peterlin, borut/0000-0001-7824-4978; Nilsson, Daniel/0000-0001-5831-385X; Hoischen, Alexander/0000-0002-8072-4476; Kong, Yong/0000-0002-2881-5274; Stitziel, Nathan/0000-0002-4963-8211; Schwartzentruber, Jeremy/0000-0002-6183-2092; Taylan, Fulya/0000-0002-2907-0235; Huss, Mikael/0000-0003-0839-2451; Yu, Timothy/0000-0003-2988-7701; Lebo, Matthew/0000-0002-9733-5207; Hart, Reece/0000-0003-3463-0775 FU Gene Partnership; Manton Center for Orphan Disease Research at Boston Children's Hospital; Center for Biomedical Informatics at Harvard Medical School FX This work was supported by funds provided through the Gene Partnership and the Manton Center for Orphan Disease Research at Boston Children's Hospital and the Center for Biomedical Informatics at Harvard Medical School and by generous donations in-kind of genomic sequencing services by Life Technologies (Carlsbad, CA, USA) and Complete Genomics (Mountain View, CA, USA). All the authors would especially like to thank the families for their participation and resulting critical contributions to this study. The study organizers would also like to thank Elizabeth Andrews and Keri Steadman for seminal contributions to the contest planning, Peter Kang for assistance tabulating patient phenotypes, Lindsay Swanson for assistance with return of results, and Elizabeth Torosian for help with manuscript preparation. This manuscript is dedicated to the memory of David Newsom. NR 69 TC 34 Z9 34 U1 2 U2 27 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 3 AR R53 DI 10.1186/gb-2014-15-3-r53 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AL2UP UT WOS:000338981300014 PM 24667040 ER PT J AU Machiela, MJ Chanock, SJ AF Machiela, Mitchell J. Chanock, Stephen J. TI GWAS is going to the dogs SO GENOME BIOLOGY LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; COMPULSIVE DISORDER; SUSCEPTIBILITY; OSTEOSARCOMA; LOCI AB Genome-wide association studies in canine models may help locate genomic susceptibility regions that are relevant to human disease. C1 [Machiela, Mitchell J.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov OI Machiela, Mitchell/0000-0001-6538-9705 NR 10 TC 2 Z9 2 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 3 AR 105 DI 10.1186/gb4166 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AL2UP UT WOS:000338981300017 PM 25002063 ER PT J AU Krishnamurthy, U Szalai, G Neelayallia, J Shen, YM Chaiworapongsa, T Hernandez-Andrade, E Than, NG Xu, ZH Yeo, L Haacke, M Romero, R AF Krishnamurthy, Uday Szalai, Gabor Neelayallia, Jaladhar Shen, Yimin Chaiworapongsa, Tinnakorn Hernandez-Andrade, Edgar Than, Nandor Gabor Xu, Zhonghui Yeo, Lami Haacke, Mark Romero, Roberto TI Quantitative T2 Changes and Susceptibility-Weighted Magnetic Resonance Imaging in Murine Pregnancy SO GYNECOLOGIC AND OBSTETRIC INVESTIGATION LA English DT Article DE Transverse relaxation time; Susceptibility-weighted imaging; Venography; Magnetic resonance imaging; Murine embryo ID HIGH-RESOLUTION MRI; PLACENTAL PERFUSION; TRANSVERSE RELAXATION; INTRAUTERINE GROWTH; EUTHERIAN MAMMALS; CONTRAST AGENT; ANIMAL-MODELS; MOUSE EMBRYOS; BLOOD-FLOW; HIGH-FIELD AB Objective: To evaluate gestational age-dependent changes in the T2 relaxation time in normal murine placentas in vivo. The role of susceptibility-weighted imaging (SWI) in visualization of the murine fetal anatomy was also elucidated. Methods: Timed-pregnant CD-1 mice at gestational day (GD) 12 and GD17 underwent magnetic resonance imaging. Multi-echo spin echo and SWI data were acquired. The placental T2 values on GD12 and GD17 were quantified. To account for the influence of systemic maternal physiological factors on placental perfusion, maternal muscle was used as a reference for T2 normalization. A linear mixed-effects model was used to fit the normalized T2 values, and the significance of the coefficients was tested. Fetal SWI images were processed and reviewed for venous vasculature and skeletal structures. Results: The average placental T2 value decreased significantly on GD17 (40.17 +/- 4.10 ms) compared to the value on GD12 (55.78 +/- 8.13 ms). The difference in normalized T2 values also remained significant (p = 0.001). Using SWI, major fetal venous structures like the cardinal vein, the subcardinal vein, and the portal vein were visualized on GD12. In addition, fetal skeletal structures could also be discerned on GD17. Conclusion: The 12 value of a normal murine placenta decreases with advancing gestation. SWI provided clear visualization of the fetal venous vasculature and bony structures. (C) 2014 S. Karger AG, Basel C1 [Krishnamurthy, Uday; Neelayallia, Jaladhar; Shen, Yimin; Haacke, Mark] Wayne State Univ, Sch Med, Dept Radiol, Detroit, MI 48201 USA. [Chaiworapongsa, Tinnakorn; Hernandez-Andrade, Edgar; Than, Nandor Gabor; Yeo, Lami] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Krishnamurthy, Uday; Neelayallia, Jaladhar; Haacke, Mark] Wayne State Univ, Coll Engn, Dept Biomed Engn, Detroit, MI 48201 USA. [Szalai, Gabor; Chaiworapongsa, Tinnakorn; Hernandez-Andrade, Edgar; Than, Nandor Gabor; Xu, Zhonghui; Yeo, Lami; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. RP Neelayallia, J (reprint author), Wayne State Univ, Sch Med, Dept Radiol, 4201 St Antoine, Detroit, MI 48201 USA. EM jneelava@med.wayne.edu; romeror@mail.nih.gov FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Department of Health and Human Services (DHHS); NICHD (NIH, DHHS) [HHSN275201300006C]; Small Business Technology Transfer (STTR) grant from the National Heart, Lung, and Blood Institute (NHLBI, NIH, DHHS) [1R42HL112580-01A1]; Wayne State University's Perinatal Research Initiative; Wayne State University's Perinatology Virtual Discovery Grant; W.K. Kellogg Foundation [P3018205] FX This research was supported in part by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), and in part by federal funds from the NICHD (NIH, DHHS) under contract No. HHSN275201300006C. The authors are grateful to Dr. Theodore Price (Perinatology Research Branch), Dr. Lisa J. Brossia-Root, Laura Lee McIntyre, and all of the personnel of the Division of Laboratory Animal Resources (Wayne State University). This work was also supported in part by a Small Business Technology Transfer (STTR) grant from the National Heart, Lung, and Blood Institute (NHLBI, NIH, DHHS; 1R42HL112580-01A1), and by Wayne State University's Perinatal Research Initiative and Perinatology Virtual Discovery Grant to J.N. (made possible by W.K. Kellogg Foundation award P3018205). NR 76 TC 3 Z9 3 U1 1 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-7346 EI 1423-002X J9 GYNECOL OBSTET INVES JI Gynecol.Obstet.Invest. PY 2014 VL 78 IS 1 BP 33 EP 40 DI 10.1159/000362552 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AL0JC UT WOS:000338812200007 PM 24861575 ER PT J AU Vieland, VJ Walters, KA Azaro, M Brzustowicz, LM Lehner, T AF Vieland, Veronica J. Walters, Kimberly A. Azaro, Marco Brzustowicz, Linda M. Lehner, Thomas TI The Value of Regenotyping Older Linkage Data Sets with Denser Marker Panels SO HUMAN HEREDITY LA English DT Article DE Linkage analysis; Data repositories; Microsatellites; SNPs; Information content; PPL ID CENTRAL-AMERICAN ANCESTRY; SCHIZOPHRENIA; GENOME; SUSCEPTIBILITY; MULTIPLE; FAMILIES; GENETICS; MEXICAN; LOCI AB Objectives: Linkage analysis can help determine regions of interest in whole-genome sequence studies. However, many linkage studies rely on older microsatellite (MSAT) panels. We set out to determine whether results would change if we regenotyped families using a dense map of SNPs. Methods: We selected 47 Hispanic-American families from the NIMH Repository and Genomics Resource (NRGR) schizophrenia data repository. We regenotyped all individuals with DNA available from the NRGR on the Affymetrix Lat Array. After optimizing SNP selection for inclusion on the linkage map, we compared information content (IC) and linkage results using MSAT, SNP and MSAT+SNP maps. Results: As expected, SNP provided a higher average IC (0.78, SD 0.03) than MSAT (0.51, SD 0.10) in a direct 'apples-to-apples' comparison using only individuals genotyped on both platforms; while MSAT + SNP provided only a slightly higher IC (0.82, SD 0.03). However, when utilizing all available individuals, including those who had genotypes available on only one platform, the IC was substantially increased using MSAT + SNP (0.76, SD 0.05) compared to SNP (0.61, SD 0.02). Linkage results changed appreciably between MSAT and MSAT + SNP in terms of magnitude, rank ordering and localization of peaks. Conclusions: Regenotyping older family data can substantially alter the conclusions of linkage analyses. (C) 2014 S. Karger AG, Basel C1 [Vieland, Veronica J.; Walters, Kimberly A.] Nationwide Childrens Hosp, Res Inst, Battelle Ctr Math Med, Columbus, OH 43215 USA. [Azaro, Marco; Brzustowicz, Linda M.] Rutgers State Univ, Dept Genet, Piscataway, NJ USA. [Lehner, Thomas] NIMH, Bethesda, MD 20892 USA. RP Vieland, VJ (reprint author), Nationwide Childrens Hosp, Res Inst, Battelle Ctr Math Med, 575 Childrens Crossrd, Columbus, OH 43215 USA. EM veronica.vieland@nationwidechildrens.org FU National Institutes of Health [R01 MH086117, U24 MH068457]; Ohio Supercomputer Center [PCCR0002] FX This work was supported by National Institutes of Health grants R01 MH086117 and U24 MH068457 and Ohio Supercomputer Center grant PCCR0002. We also wish to thank the investigators who contributed these data sets to the NRGR and the families who participated in these studies. NR 18 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2014 VL 78 IS 1 BP 9 EP 16 DI 10.1159/000360003 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA AL7OA UT WOS:000339322500002 PM 24969307 ER PT J AU Bekker, LG Slack, C Lee, S Shah, S Kapogiannis, B AF Bekker, Linda-Gail Slack, Catherine Lee, Sonia Shah, Seema Kapogiannis, Bill TI Ethical Issues in Adolescent HIV Research in Resource-Limited Countries SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adolescents; ethics; informed consent ID PREEXPOSURE PROPHYLAXIS; PREVENTION RESEARCH; CLINICAL-RESEARCH; VACCINE TRIAL; SOUTH-AFRICA; YOUTH; RISK; PARTICIPATION; INCLUSION; STANDARDS AB Globally, there are 5 million young people aged 15-24 years living with HIV, and many more millions are at risk for HIV acquisition. Compelling research questions exist that require the involvement of young people and other vulnerable populations in HIV-related research in diverse settings around the world. Despite this, there remains a reluctance to involve adolescent participants, including young women, in clinical research. Complex and, at times, contradictory legal and ethical requirements can be a challenge. Ethical benchmarks can be applied to ensure that research meets high-level standards and is planned for appropriately. C1 [Bekker, Linda-Gail] Univ Cape Town, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa. [Slack, Catherine] UKZN, Coll Humanities, Sch Appl Human Sci, HIV AIDS Vaccines Eth Grp, Pietermaritzburg, South Africa. [Lee, Sonia; Kapogiannis, Bill] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, Bethesda, MD USA. [Shah, Seema] NIAID, NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Shah, Seema] NIAID, Div Aids, Bethesda, MD 20892 USA. RP Bekker, LG (reprint author), Univ Cape Town, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa. EM Linda-gail.bekker@hiv-research.org.za FU NIH Clinical Center; NIAID; South African AIDS Vaccine Initiative (SAAVI); National Institutes of Health [1RO1 A1094586] FX This research was supported in part by the Intramural Research Program of the NIH Clinical Center and by NIAID, and received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The opinions expressed are the views of the authors. They do not represent any position or policy of the US National Institutes of Health, the Public Health Service, or the Department of Health and Human Services.; Funding was also provided to C. Slack by the South African AIDS Vaccine Initiative (SAAVI) and by the National Institutes of Health award (1RO1 A1094586) CHAMPS (Choices for Adolescent Methods of Prevention in South Africa). NR 40 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2014 VL 65 SU 1 BP S24 EP S28 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL3IF UT WOS:000339019600007 PM 24321980 ER PT J AU Dawson, L Klingman, KL Marrazzo, J AF Dawson, Liza Klingman, Karin L. Marrazzo, Jeanne TI Addressing Standards of Care in Resource-Limited Settings SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE standard of care; treatment guidelines; quality of care; HIV/AIDS; antiretroviral therapy; prevention ID HIV PREVENTION TRIALS; UNDUE INDUCEMENT; DOSE NEVIRAPINE; SOUTH-AFRICA; TRANSMISSION; EXPERIENCES; INFECTION; CHILDREN; WOMEN AB The choice between "best-known" standards of care (SOC) or "best available" standards as the control arm in a clinical trial is a fundamental dilemma in clinical research in resource-limited settings (RLS). When the health system is delivering less than an optimal level of care, using highest standard of care in a clinical trial may produce results that cannot be implemented or sustained locally. On the other hand, using interventions that are more feasible in the local setting may involve suboptimal care, and clinical outcomes may be affected. The need for improved standards in health systems in RLS, and the difficulty in securing them, has led many researchers advocate for policy changes at the national or international level to improve clinical care more systemically. SOC decisions in a clinical trial affect the level of benefit provided to study participants and the policy implications of the trial findings. SOC choices should provide high-quality care to help advance the health care system in host countries participating in the trial, but balancing the scientific and ethical objectives of SOC choices is difficult, and there is no single formula for selecting the appropriate SOC. Despite the challenges, well-designed and conducted clinical trials can and should make significant contributions to health systems in RLS. C1 [Dawson, Liza; Klingman, Karin L.] NIAID, Div AIDS, NIH, Bethesda, MD 20817 USA. [Marrazzo, Jeanne] Univ Washington, Dept Med, Div Allergy & Infect Dis, Seattle, WA USA. RP Dawson, L (reprint author), NIAID, Div AIDS, NIH, Room 4147A,6700B Rockledge Dr, Bethesda, MD 20817 USA. EM dawsonl@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 22 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2014 VL 65 SU 1 BP S10 EP S14 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL3IF UT WOS:000339019600004 PM 24321977 ER PT J AU Farley, JE Landers, TF Godfrey, C Lipke, V Sugarman, J AF Farley, Jason E. Landers, Timothy F. Godfrey, Catherine Lipke, Virginia Sugarman, Jeremy TI Optimizing the Protection of Research Participants and Personnel in HIV-Related Research Where TB Is Prevalent: Practical Solutions for Improving Infection Control SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE infection control; TB; HIV; clinical research; human subjects protections; ethics ID DRUG-RESISTANT TUBERCULOSIS; ISONIAZID PREVENTIVE THERAPY; HEALTH-CARE WORKERS; SOUTH-AFRICA; PULMONARY TUBERCULOSIS; ANTIRETROVIRAL THERAPY; MULTIDRUG-RESISTANT; TRANSMISSION; IMPLEMENTATION; DISINFECTION AB Tuberculosis (TB) is a leading cause of death among persons with HIV globally. HIV-related research in TB endemic areas raises some unique and important ethical issues in infection control related to protecting both research participants and personnel. To address such concerns, this article provides practical guidance to help research teams develop strategies to prevent TB transmission in studies involving persons with HIV in TB endemic settings. C1 [Farley, Jason E.] Johns Hopkins Univ, Sch Nursing, Dept Community & Publ Hlth, Baltimore, MD 21205 USA. [Farley, Jason E.; Sugarman, Jeremy] Johns Hopkins Ctr AIDS Res CFAR, Baltimore, MD USA. [Landers, Timothy F.] Ohio State Univ, Coll Nursing, Columbus, OH 43210 USA. [Godfrey, Catherine] NIAID, NIH, Bethesda, MD 20892 USA. [Lipke, Virginia] Ctr Dis Control & Prevent, Div Global HIV AIDS GAP, Atlanta, GA USA. [Sugarman, Jeremy] Johns Hopkins Berman Inst Bioeth, Baltimore, MD USA. [Sugarman, Jeremy] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. RP Farley, JE (reprint author), Johns Hopkins Univ, Sch Nursing, 525 N Wolfe St,Suite 525, Baltimore, MD 21205 USA. EM jfarley1@jhu.edu FU National Institutes of Health (NIH) [1P30AI094189]; NIH - National Institute of Allergy and Infectious Disease; NIH - NCI; NIH - National Institute of Child Health and Human Development; NIH - National Heart, Lung, and Blood Institute; NIH - National Institute of Drug Abuse; NIH - National Institute of Mental Health; NIH - National Institute on Aging; NIH - FIC; NIH - OAR; National Institute of Allergy and Infectious Disease; National Institute of Drug Abuse; National Institute of Mental Health [UM1AI068619] FX This publication proposal was made possible with help from the Johns Hopkins University Center for AIDS Research, a National Institutes of Health (NIH)-funded program (1P30AI094189), which is supported by the following NIH cofunding and participating Institutes and Centers: National Institute of Allergy and Infectious Disease, NCI, National Institute of Child Health and Human Development, National Heart, Lung, and Blood Institute, National Institute of Drug Abuse, National Institute of Mental Health, National Institute on Aging, FIC, and OAR. Work on this article was also supported in part by the National Institute of Allergy and Infectious Disease, National Institute of Drug Abuse and the National Institute of Mental Health under Cooperative Agreement # UM1AI068619 to the HIV Prevention Trials Network. NR 40 TC 2 Z9 2 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2014 VL 65 SU 1 BP S19 EP S23 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL3IF UT WOS:000339019600006 PM 24321979 ER PT J AU Fitzgibbon, JE Wallis, CL AF Fitzgibbon, Joseph E. Wallis, Carole L. TI Laboratory Challenges Conducting International Clinical Research in Resource-Limited Settings SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE Good Clinical Laboratory Practice; GCLP; quality management; resource-limited settings; HIV; tuberculosis ID SUB-SAHARAN AFRICA; HEALTH; QUALITY; SYSTEMS; CARE; HIV AB There are many challenges to performing clinical research in resource-limited settings. Here, we discuss several of the most common laboratory issues that must be addressed. These include issues relating to organization and personnel, laboratory facilities and equipment, standard operating procedures, external quality assurance, shipping, laboratory capacity, and data management. Although much progress has been made, innovative ways of addressing some of these issues are still very much needed. C1 [Fitzgibbon, Joseph E.] NIAID, Drug Dev & Clin Sci Branch, Therapeut Res Program, Div AIDS,NIH, Bethesda, MD 20892 USA. [Wallis, Carole L.] Lancet Labs, Specialty Mol Div, Johannesburg, South Africa. RP Fitzgibbon, JE (reprint author), NIAID, Drug Dev & Clin Sci Branch, Therapeut Res Program, Div AIDS,NIH, Room 5151,6700B Rockledge Dr, Bethesda, MD 20892 USA. EM jfitzgibbon@niaid.nih.gov FU National Institutes of Health from the National Institute of Allergy and Infectious Diseases [UM1AI068636-07] FX Supported in part by National Institutes of Health Grant UM1AI068636-07 from the National Institute of Allergy and Infectious Diseases to C.L.W. NR 11 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2014 VL 65 SU 1 BP S36 EP S39 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL3IF UT WOS:000339019600010 PM 24321984 ER PT J AU Godfrey, C Schouten, JT Swindells, S AF Godfrey, Catherine Schouten, Jeffrey T. Swindells, Susan TI Implementation of HIV-Related Clinical Research in the International Setting SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Editorial Material DE International clinical research; Implementation; ACTG ID SINGLE-DOSE NEVIRAPINE; ANTIRETROVIRAL THERAPY; INFECTED ADULTS; PREVENTION; TUBERCULOSIS; PARTNERSHIPS; REGIMENS; SITES C1 [Godfrey, Catherine] NIAID, HIV Res Branch, Div AIDS, NIH, Bethesda, MD 20892 USA. [Schouten, Jeffrey T.] Fred Hutchinson Canc Res Ctr, Off HIV AIDS Network Coordinat, Seattle, WA 98104 USA. [Swindells, Susan] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE 68198 USA. RP Swindells, S (reprint author), Univ Nebraska Med Ctr, 988106 Nebraska Med Ctr, Omaha, NE 68198 USA. EM sswindells@unmc.edu FU NIAID NIH HHS [AI 068636, U01 AI068614, U01 AI068636, UM1 AI068636, UM01 AI068614, UM1 AI068614] NR 16 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2014 VL 65 SU 1 BP S1 EP S2 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL3IF UT WOS:000339019600001 PM 24321976 ER PT J AU Godfrey, C Schouten, JT AF Godfrey, Catherine Schouten, Jeffrey T. TI Infection Control Best Practices in Clinical Research in Resource-Limited Settings SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE infection control; resource-limited setting; hand hygiene; occupational health ID CARE-ASSOCIATED INFECTIONS; OF-THE-LITERATURE; HAND HYGIENE; CONTROL PROGRAMS; SHARPS INJURIES; HEALTH; VARICELLA; PREVENTION; WORKERS; SAFETY AB Infection control activities in the international research setting include the development of meaningful and effective policies on specific topics such as hand and respiratory hygiene. Prevention of infection in health care workers and management of occupational exposure to transmissible agents are important aspects of the role of an infection control practitioner. Hand hygiene reduces health care associated infections and practices may be implemented in the research setting. C1 [Godfrey, Catherine] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. [Schouten, Jeffrey T.] Fred Hutchinson Canc Res Ctr, Off HIV AIDS Network Coordinat, Seattle, WA 98104 USA. RP Godfrey, C (reprint author), NIAID, NIH, 6700B Rockledge Dr, Bethesda, MD 20892 USA. EM cgodfrey@niaid.nih.gov FU Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [UM01 AI068614]; National Institute of Mental Health FX The Office of HIV/AIDS Network Coordination has been funded in whole or in part with Federal funds from the Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, grant number UM01 AI068614, entitled Leadership Group for a Global HIV Vaccine Clinical Trials (Office of HIV/AIDS Network Coordination) with additional support from the National Institute of Mental Health. NR 54 TC 1 Z9 1 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2014 VL 65 SU 1 BP S15 EP S18 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL3IF UT WOS:000339019600005 PM 24321978 ER PT J AU Godfrey, C Payton, M Tasker, S Proestel, S Schouten, JT AF Godfrey, Catherine Payton, Manizhe Tasker, Sybil Proestel, Scott Schouten, Jeffrey T. TI Ensuring Participant Safety and Trial Integrity With Clinical Trials Oversight SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE quality management; pharmacovigilance; monitoring; clinical trials oversight ID SETTINGS; QUALITY AB Clinical trial oversight is a critical element that ensures the protection of research participants and integrity of the data collected. The trial sponsor, a local Institutional Review Board, and independent monitoring committees all contribute with complementary but overlapping responsibilities. Consistency among these groups is essential for the smooth conduct of a clinical trial but may be challenging in resource-limited settings (RLS). Capacity building and training for RLS may improve clinical trials oversight and ultimately medical management. In this article, we review the components necessary for optimal clinical trial oversight and the issues that arise in the RLS, with some suggested strategies for improvement. C1 [Godfrey, Catherine; Payton, Manizhe; Proestel, Scott] NIAID, HIV Res Branch, NIH, Bethesda, MD 20892 USA. [Godfrey, Catherine; Payton, Manizhe; Proestel, Scott] NIAID, Off Clin Site Oversight, Div AIDS, NIH, Bethesda, MD 20892 USA. [Tasker, Sybil] PRA Int, Raleigh, NC USA. [Schouten, Jeffrey T.] Fred Hutchinson Canc Res Ctr, Off HIV AIDS Network Coordinat, Seattle, WA 98104 USA. RP Godfrey, C (reprint author), NIAID, NIH, 6700B Rockledge Dr, Bethesda, MD 20892 USA. EM cgodfrey@niaid.nih.gov FU Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [UM01 AI068614]; National Institute of Mental Health FX The Office of HIV/AIDS Network Coordination has been funded in whole or in part with Federal funds from the Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, grant number UM01 AI068614, entitled Leadership Group for a Global HIV Vaccine Clinical Trials (Office of HIV/AIDS Network Coordination) with additional support from the National Institute of Mental Health. NR 20 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2014 VL 65 SU 1 BP S40 EP S43 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL3IF UT WOS:000339019600011 PM 24321985 ER PT J AU Holmes, CB Sikazwe, I Raelly, RL Freeman, BL Wambulawae, I Silwizya, G Topp, SM Chilengi, R Henostroza, G Kapambwe, S Simbeye, D Sibajene, S Chi, H Godfrey, K Chi, B Moore, CB AF Holmes, Charles B. Sikazwe, Izukanji Raelly, Roselyne L. Freeman, Bethany L. Wambulawae, Inonge Silwizya, Geoffrey Topp, Stephanie M. Chilengi, Roma Henostroza, German Kapambwe, Sharon Simbeye, Darius Sibajene, Sheila Chi, Harmony Godfrey, Katy Chi, Benjamin Moore, Carolyn Bolton TI Managing Multiple Funding Streams and Agendas to Achieve Local and Global Health and Research Objectives: Lessons From the Field SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE development assistance for health; operational management; PEPFAR; funding sources; monitoring and evaluation ID DEVELOPMENT ASSISTANCE; ZAMBIA AB Multiple funding sources provide research and program implementation organizations a broader base of funding and facilitate synergy, but also entail challenges that include varying stakeholder expectations, unaligned grant cycles, and highly variable reporting requirements. Strong governance and strategic planning are essential to ensure alignment of goals and agendas. Systems to track budgets and outputs, as well as procurement and human resources are required. A major goal of funders is to transition leadership and operations to local ownership. This article details successful approaches used by the newly independent nongovernmental organization, the Centre for Infectious Disease Research in Zambia. C1 [Holmes, Charles B.; Sikazwe, Izukanji; Raelly, Roselyne L.; Freeman, Bethany L.; Wambulawae, Inonge; Silwizya, Geoffrey; Topp, Stephanie M.; Chilengi, Roma; Henostroza, German; Kapambwe, Sharon; Simbeye, Darius; Sibajene, Sheila; Chi, Harmony; Chi, Benjamin; Moore, Carolyn Bolton] Univ N Carolina, Ctr Infect Dis Res Zambia, Chapel Hill, NC USA. [Holmes, Charles B.; Sikazwe, Izukanji; Freeman, Bethany L.; Chi, Harmony; Chi, Benjamin; Moore, Carolyn Bolton] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Henostroza, German] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Godfrey, Katy] NIAID, Div Acquired Immunodeficiency Syndrome, Bethesda, MD USA. RP Holmes, CB (reprint author), Univ N Carolina, Ctr Infect Dis Res Zambia, Plot 5032 Great North Rd, Lusaka, Zambia. EM charles.holmes@cidrz.org FU NIAID NIH HHS [U01 AI068636, UM1 AI068636] NR 18 TC 1 Z9 1 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2014 VL 65 SU 1 BP S32 EP S35 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL3IF UT WOS:000339019600009 PM 24321983 ER PT J AU Whalen, CJ Donnell, D Tartakovsky, M AF Whalen, Christopher J. Donnell, Deborah Tartakovsky, Michael TI Supporting Research Sites in Resource-Limited Settings: Challenges in Implementing Information Technology Infrastructure SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE information technology; research infrastructure; data management; electronic data capture; mHealth; mobile technology AB As information and communication technology infrastructure becomes more reliable, new methods of electronic data capture, data marts/data warehouses, and mobile computing provide platforms for rapid coordination of international research projects and multisite studies. However, despite the increasing availability of Internet connectivity and communication systems in remote regions of the world, there are still significant obstacles. Sites with poor infrastructure face serious challenges participating in modern clinical and basic research, particularly that relying on electronic data capture and Internet communication technologies. This report discusses our experiences in supporting research in resource-limited settings. We describe examples of the practical and ethical/regulatory challenges raised by the use of these newer technologies for data collection in multisite clinical studies. C1 [Whalen, Christopher J.; Tartakovsky, Michael] NIAID, Off CyberInfrastruct & Computat Biol, NIH, Bethesda, MD 20814 USA. [Donnell, Deborah] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Whalen, CJ (reprint author), NIAID, Off CyberInfrastruct & Computat Biol, NIH, 6610 Rockledge Dr,Suite 2102, Bethesda, MD 20814 USA. EM cwhalen@mail.nih.gov FU HIV Prevention Trials Network; National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Mental Health; National Institute of Drug Abuse, Office of AIDS Research, of the National Institutes of Health, Department of Health and Human Services [UM1-AI068617]; Office of Science Management and Operations of the NIAID, Bethesda, MD FX Portions of this research was supported by the HIV Prevention Trials Network, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Mental Health, and the National Institute of Drug Abuse, Office of AIDS Research, of the National Institutes of Health, Department of Health and Human Services through grants (UM1-AI068617) (D.D.). This research was also supported in part by the Office of Science Management and Operations of the NIAID, Bethesda, MD. NR 19 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2014 VL 65 SU 1 BP S44 EP S49 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL3IF UT WOS:000339019600012 PM 24321986 ER PT J AU Li, W Rallabhandi, S AF Li, Wu Rallabhandi, Sriram TI Inverse Design of Low-Boom Supersonic Concepts Using Reversed Equivalent-Area Targets SO JOURNAL OF AIRCRAFT LA English DT Article ID OPTIMIZATION AB A promising path for developing a low-boom configuration is a multifidelity approach that starts from a low-fidelity low-boom design, refines the low-fidelity design with computational fluid dynamics equivalent-area analysis, and improves the design with sonic-boom analysis by using computational fluid dynamics off-body pressure distributions. The focus of this paper is on the third step of this approach, in which the design is improved with sonic-boom analysis through the use of computational fluid dynamics calculations. A new inverse design process for off-body pressure tailoring is formulated and demonstrated with a low-boom supersonic configuration that was developed by using the mixed-fidelity design method with computational fluid dynamics equivalent-area analysis. The new inverse design process uses the reverse propagation of the pressure distribution from a mid-field location to a near-field location, converts the near-field into an equivalent-area distribution, generates a low-boom target for the reversed equivalent area of the configuration, and modifies the configuration to minimize the differences between the configuration's reversed equivalent area and the low-boom target. The new inverse design process is used to modify a supersonic demonstrator concept for a cruise Mach number of 1.6 and a cruise weight of 30,000 Ib. The modified configuration has a fully shaped ground signature that has a perceived loudness value of 78.5, whereas the original configuration has a partially shaped aft signature with a perceived loudness of 82.3. C1 [Li, Wu] NASA, Langley Res Ctr, Aeronaut Syst Anal Branch, Hampton, VA 23681 USA. [Rallabhandi, Sriram] NIA, Aeronaut Syst Anal Branch, Hampton, VA 23666 USA. RP Li, W (reprint author), NASA, Langley Res Ctr, Aeronaut Syst Anal Branch, Mail Stop 442, Hampton, VA 23681 USA. NR 15 TC 2 Z9 2 U1 1 U2 5 PU AMER INST AERONAUTICS ASTRONAUTICS PI RESTON PA 1801 ALEXANDER BELL DRIVE, STE 500, RESTON, VA 22091-4344 USA SN 0021-8669 EI 1533-3868 J9 J AIRCRAFT JI J. Aircr. PD JAN-FEB PY 2014 VL 51 IS 1 BP 29 EP 36 DI 10.2514/1.C031551 PG 8 WC Engineering, Aerospace SC Engineering GA AL2RP UT WOS:000338973100003 ER PT J AU Rudrabhatla, P AF Rudrabhatla, Parvathi TI Regulation of Neuronal Cytoskeletal Protein Phosphorylation in Neurodegenerative Diseases SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Axonal transport; cytoskeleton; neurofilament; PP2A; proline-directed kinases; synuclein; tangles; tau; TDP43 ID AMYOTROPHIC-LATERAL-SCLEROSIS; PAIRED HELICAL FILAMENTS; CYCLIN-DEPENDENT KINASE-5; SLOW AXONAL-TRANSPORT; ABERRANT NEUROFILAMENT PHOSPHORYLATION; FRONTOTEMPORAL LOBAR DEGENERATION; GLYCOGEN-SYNTHASE KINASE-3-BETA; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; TAU-PROTEIN AB Neuronal cytoskeletal proteins such as neurofilaments (NFs) and tau are aberrantly and hyperphosphorylated in neurodegeneration. Under normal physiological conditions, NFs are synthesized in the cell bodies and phosphorylated and transported in the axonal compartment. However, under neurodegenerative disorders such as Alzheimer's disease (AD), spinal cord motor neuron inclusions of amyotrophic lateral sclerosis, Lewy bodies of Parkinson's disease, Pick's disease, Charcot-Marie-Tooth disease, and diabetic neuropathy, NFs are aberrantly and hyperphosphorylated in cell bodies. The proline directed protein kinases, such as cyclin-dependent protein kinase 5, mitogen activated protein kinase, and glycogen synthase kinase 3 beta, and the non proline-directed kinases, such as casein kinase 1, are deregulated in AD. Moreover, the reversible phosphorylation by protein phosphatase, PP2A, which mainly carries out the dephosphorylation of tau and NFs, is down regulated in AD brain. The aberrant phosphorylation of cytoskeletal proteins such as tau and NFs results in the axonal transport defects in neurodegeneration. The peptidyl-prolyl isomerase Pin1 plays a regulatory role in the post-phosphorylation mechanism of neuronal cytoskeletal proteins in AD brain. Possible therapeutic interventions for neurodegenerative disorders are 1) inhibition of proline-directed kinases, 2) activation of protein phosphatases such as PP2A, and 3) modulation of peptidyl-prolyl isomerases such as Pin1. Here, I discuss the regulation of neuronal cytoskeletal proteins under physiology and pathology. C1 [Rudrabhatla, Parvathi] NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. [Rudrabhatla, Parvathi] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Rudrabhatla, P (reprint author), NINDS, Neurochem Lab, Neurobiol Lab, NIH, Bldg 49,Room 3A63, Bethesda, MD 20892 USA. EM parvathir@ninds.nih.gov FU NINDS; NIH FX I acknowledge Dr. Alan Koretsky, NINDS for his support. I thank Dr. Harish C. Pant. This work is supported by intramural grants of NINDS, NIH. NR 142 TC 9 Z9 10 U1 3 U2 14 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 41 IS 3 BP 671 EP 684 DI 10.3233/JAD-130794 PG 14 WC Neurosciences SC Neurosciences & Neurology GA AL7QG UT WOS:000339329100005 PM 24748119 ER PT J AU Miller, B Vaughn, S Freund, LS AF Miller, Brett Vaughn, Sharon Freund, Lisa S. TI Learning Disabilities Research Studies: Findings From NICHD-Funded Projects SO JOURNAL OF RESEARCH ON EDUCATIONAL EFFECTIVENESS LA English DT Editorial Material ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; READING DIFFICULTIES; SCHOOL STUDENTS; INTERVENTION; DYSLEXIA; CHILDREN; SYSTEMS; READERS; MATTER C1 [Miller, Brett; Freund, Lisa S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Vaughn, Sharon] Univ Texas Austin, Austin, TX 78712 USA. RP Miller, B (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 6100 Execut Blvd,Suite 4B05,MSC 7510, Bethesda, MD 20892 USA. EM brett.miller@nih.gov FU NICHD NIH HHS [P50 HD052117] NR 30 TC 2 Z9 2 U1 1 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1934-5747 EI 1934-5739 J9 J RES EDUC EFF JI J. Res. Educ. Eff. PY 2014 VL 7 IS 3 SI SI BP 225 EP 231 DI 10.1080/19345747.2014.927251 PG 7 WC Education & Educational Research SC Education & Educational Research GA AL2XW UT WOS:000338990000001 PM 25485027 ER PT S AU Marton, Z Bhandari, HB Wen, HH Nagarkar, VV AF Marton, Zsolt Bhandari, Harish B. Wen, Harold H. Nagarkar, Vivek V. BE Whiting, BR Hoeschen, C Kontos, D TI Multi layer coated gratings for phase-contrast computed tomography (CT) SO MEDICAL IMAGING 2014: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging - Physics of Medical Imaging CY FEB 17-20, 2014 CL San Diego, CA SP Soc Photo Opt Instrumentat Engn, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med, Caresteam, GE Healthcare DE Phase contrast imaging; X-ray gratings; Multi layers; Electron-beam evaporation AB By using the principle of grating interferometry, X-ray phase contrast imaging can now be performed with incoherent radiation from standard X-ray tube. This approach is in stark contrast with imaging methods using coherent synchrotron X-ray sources or micro-focus sources to improve contrast. The gratings interferometer imaging technique is capable of measuring the phase shift of hard X-rays travelling through a sample, which greatly enhances the contrast of low absorbing specimen compared to conventional amplitude contrast images. The key components in this approach are the gratings which consists of alternating layers of high and low Z (atomic number) materials fabricated with high aspect ratios. Here we report on a novel method of fabricating the grating structures using the technique of electron-beam (e-beam) thin film deposition. Alternating layers of silicon (Z=14) and tungsten (Z=74) were deposited, each measuring 100 nm each, on a specially designed echelle substrate, which resulted in an aspect ratio of similar to 100:1. Fabrication parameters related to the thin film deposition such as geometry, directionality, film adhesion, stress and the resulting scanning electron micrographs will be discussed in detail. Using e-beam method large-area gratings with precise multilayer coating thicknesses can be fabricated economically circumventing the expensive lithography steps. C1 [Marton, Zsolt; Bhandari, Harish B.; Nagarkar, Vivek V.] Radiat Monitoring Devices Inc, Watertown, MA 02472 USA. [Wen, Harold H.] NHLBI, Lab Imaging Phys, Bethesda, MD 20892 USA. RP Marton, Z (reprint author), Radiat Monitoring Devices Inc, Watertown, MA 02472 USA. EM ZMarton@RMDInc.com FU NIH NHLBI SBIR [HHSN268201200077C] FX This work was supported by NIH NHLBI SBIR Phase I contract number HHSN268201200077C. We thank Dave Ventola and John Seney for useful discussions and for helping us prepare the multilayer gratings. We appreciate the use of Optometrics Corporation's electron beam facilities (Ayer, MA). NR 1 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9826-7 J9 PROC SPIE PY 2014 VL 9033 AR UNSP 90334Z DI 10.1117/12.2043967 PG 6 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BA8VD UT WOS:000338775800170 ER PT S AU Chen, XB Winters, C Azzam, R Sousa, AA Leapman, RD Reese, TS AF Chen, Xiaobing Winters, Christine Azzam, Rita Sousa, Alioscka A. Leapman, Richard D. Reese, Thomas S. BE Nagerl, UV Triller, A TI Nanoscale Imaging of Protein Molecules at the Postsynaptic Density SO NANOSCALE IMAGING OF SYNAPSES: NEW CONCEPTS AND OPPORTUNITIES SE Neuromethods LA English DT Article; Book Chapter DE EM tomography; Immuno-EM; High-pressure freezing; Freeze-substitution; Hippocampal cultures; Synapses; Postsynaptic density; PSD-95; RNAi ID ACTIVE ZONE MATERIAL; AMPA RECEPTORS; CRYOELECTRON TOMOGRAPHY; ELECTRON TOMOGRAPHY; NEUROMUSCULAR-JUNCTION; PRESYNAPTIC MEMBRANE; SCAFFOLDING PROTEINS; TRANSMITTER RELEASE; HIPPOCAMPAL-NEURONS; RAT HIPPOCAMPUS AB The postsynaptic density (PSD) is a large macromolecular machine that lines the postsynaptic membrane at glutamatergic synapses. The PSD is responsible for synaptic transmission, signal transduction, and processing and provides a substrate for synaptic plasticity. Here we describe approaches to unravel the molecular organization of the PSD to gain insights into its synaptic function. Dissociated cultures of rat hippocampal neurons are prepared by high-pressure freezing followed by freeze-substitution and low-temperature embedding to maximize preservation of fragile structures. Dual-axis EM tomographic reconstructions of spine synapses are performed on sections 100-200 nm thick to visualize details obscured by structural overlap prevalent in conventional electron micrographs. EM tomographic analyses show that the PSD proteins are organized as an orthogonal assembly constituting the core of the PSD. Immunogold EM coupled with tomography identifies a class of membrane-associated vertical filaments in the PSD core as PSD-95, the major scaffolding protein. Acute knockdown of PSD-95 with RNAi leads to loss of patches of electrondense PSD material, including loss of vertical filaments and their associated structures demonstrating its key role in the PSD core. The tomographic analyses so far have been limited to sections thinner than the diameter of a PSD, but newly developed scanning transmission electron microscopy tomography permits reconstructions of entire PSDs in dendritic spines in sections 1-2 mu m thick. The overall structure of entire PSD can now be analyzed to delineate how elimination of key PSD proteins might affect its overall structure. C1 [Chen, Xiaobing; Winters, Christine; Azzam, Rita; Reese, Thomas S.] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. [Sousa, Alioscka A.; Leapman, Richard D.] Natl Inst Biol Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD USA. RP Chen, XB (reprint author), NINDS, Neurobiol Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 85 TC 2 Z9 2 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 0893-2336 BN 978-1-4614-9179-8; 978-1-4614-9178-1 J9 NEUROMETHODS JI Neuromethods PY 2014 VL 84 BP 1 EP 21 DI 10.1007/978-1-4614-9179-8_1 D2 10.1007/978-1-4614-9179-8 PG 21 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA BA6EH UT WOS:000337113300002 ER PT J AU Chylinski, K Makarova, KS Charpentier, E Koonin, EV AF Chylinski, Krzysztof Makarova, Kira S. Charpentier, Emmanuelle Koonin, Eugene V. TI Classification and evolution of type II CRISPR-Cas systems SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ADAPTIVE BACTERIAL IMMUNITY; SHORT PALINDROMIC REPEATS; ONE-STEP GENERATION; STREPTOCOCCUS-THERMOPHILUS; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; GENE-EXPRESSION; PROTEIN CSN2; RNA; DNA AB The CRISPR-Cas systems of archaeal and bacterial adaptive immunity are classified into three types that differ by the repertoires of CRISPR-associated (cas) genes, the organization of cas operons and the structure of repeats in the CRISPR arrays. The simplest among the CRISPR-Cas systems is type II in which the endonuclease activities required for the interference with foreign deoxyribonucleic acid (DNA) are concentrated in a single multidomain protein, Cas9, and are guided by a co-processed dual-tracrRNA: crRNA molecule. This compact enzymatic machinery and readily programmable site-specific DNA targeting make type II systems top candidates for a new generation of powerful tools for genomic engineering. Here we report an updated census of CRISPR-Cas systems in bacterial and archaeal genomes. Type II systems are the rarest, missing in archaea, and represented in similar to 5% of bacterial genomes, with an over-representation among pathogens and commensals. Phylogenomic analysis suggests that at least three cas genes, cas1, cas2 and cas4, and the CRISPR repeats of the type II-B system were acquired via recombination with a type I CRISPR-Cas locus. Distant homologs of Cas9 were identified among proteins encoded by diverse transposons, suggesting that type II CRISPR-Cas evolved via recombination of mobile nuclease genes with type I loci. C1 [Chylinski, Krzysztof; Charpentier, Emmanuelle] Umea Univ, Lab Mol Infect Med Sweden MIMS, UCMR, Dept Mol Biol, S-90187 Umea, Sweden. [Chylinski, Krzysztof] Univ Vienna, Max F Perutz Labs, A-1030 Vienna, Austria. [Makarova, Kira S.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Charpentier, Emmanuelle] Helmholtz Ctr Infect Res, Dept Regulat Infect Biol, D-38124 Braunschweig, Germany. [Charpentier, Emmanuelle] Hannover Med Sch, D-30625 Hannover, Germany. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU US Department of Health and Human Services; Swedish Research Council [K2010-57X-21436-01-3, K2013-57X-21436-04-3, 621-2011-5752-LiMS]; Kempe Foundation [SMK-1136.1]; Ume a University [223-272810, 223-2836-10, 223-2989-10]; Laboratory for Molecular Infection Medicine Sweden; Ume a Centre for Microbial Research; Helmholtz Association; Alexander von Humboldt Foundation; Federal Ministry of Education and Research FX US Department of Health and Human Services (tothe National Library of Medicine) [K. S. M., E. V. K.]; Swedish Research Council [K2010-57X-21436-01-3, K2013-57X-21436-04-3, 621-2011-5752-LiMS to E. C.]; Kempe Foundation [#SMK-1136.1]; Ume a University [Dnr: 223-272810, Dnr: 223-2836-10, Dnr: 223-2989-10 to E. C.]; Laboratory for Molecular Infection Medicine Sweden, the Ume a Centre for Microbial Research, the Helmholtz Association and the Alexander von Humboldt Foundation, Federal Ministry of Education and Research [E. C.]. Funding for open access charge: US Department of Health and Human Services (to the National Library of Medicine); Swedish Research Council [K2010-57X-21436-01-3, K2013-57X-21436-04-3, 621-2011-5752-LiMS]; Kempe Foundation; Ume a University [Dnr: 223-2728-10, Dnr: 223-2836-10, Dnr: 223-2989-10]. NR 83 TC 80 Z9 88 U1 16 U2 83 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 10 BP 6091 EP 6105 DI 10.1093/nar/gku241 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AK9SW UT WOS:000338768100008 PM 24728998 ER PT J AU Prasad, R Horton, JK Chastain, PD Gassman, NR Freudenthal, BD Hou, EW Wilson, SH AF Prasad, Rajendra Horton, Julie K. Chastain, Paul D., II Gassman, Natalie R. Freudenthal, Bret D. Hou, Esther W. Wilson, Samuel H. TI Suicidal cross-linking of PARP-1 to AP site intermediates in cells undergoing base excision repair SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-POLYMERASE-BETA; SINGLE-STRAND BREAKS; POLY(ADP-RIBOSE) POLYMERASE-1; SUBSTRATE-SPECIFICITY; MOUSE FIBROBLASTS; TOPOISOMERASE-I; BINDING; DAMAGE; MECHANISM; PROTEINS AB Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme in mammalian cells. The enzyme synthesizes polymers of ADP-ribose from the coenzyme NAD+ and plays multifaceted roles in cellular responses to genotoxic stress, including DNA repair. It had been shown that mouse fibroblasts treated with a DNA methylating agent in combination with a PARP inhibitor exhibit higher cytotoxicity than cells treated with methylating agent alone. This lethality of the PARP inhibitor is dependent on apurinic/apyrimidinic (AP) sites in the DNA and the presence of PARP-1. Here, we show that purified PARP-1 is capable of forming a DNA-protein cross-link (DPC) by covalently attaching to the AP site. This DPC formation is specific to the presence of the natural AP site in DNA and is accompanied by a single-strand DNA incision. Cellular studies confirm the formation of PARP-1 DPCs during alkylating agent-induced base excision repair (BER) and formation of DPCs is enhanced by a PARP inhibitor. Using an N-terminal and C-terminal truncated PARP-1 we show that a polypeptide fragment comprising the zinc 3 and BRCT sub-domains is sufficient for DPC formation. The covalent attachment of PARP-1 to AP site-containing DNA appears to be a suicidal event when BER is overwhelmed or disrupted. C1 [Prasad, Rajendra; Horton, Julie K.; Gassman, Natalie R.; Freudenthal, Bret D.; Hou, Esther W.; Wilson, Samuel H.] NIEHS, Lab Struct Biol, NIH, Res Triangle Pk, NC 27709 USA. [Chastain, Paul D., II] William Carey Univ, Coll Osteopath Med, Hattiesburg, MS 39401 USA. RP Wilson, SH (reprint author), NIEHS, Lab Struct Biol, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov OI Gassman, Natalie/0000-0002-8488-2332 FU National Institutes of Health, National Institute of Environmental Health Sciences [Z01ES050158, Z01 ES050159]; Laboratory of Structural Biology, NIEHS FX Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences [Z01ES050158, Z01 ES050159] (in part). Funding for open access charge: Laboratory of Structural Biology, NIEHS. NR 62 TC 15 Z9 15 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 10 BP 6337 EP 6351 DI 10.1093/nar/gku288 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AK9SW UT WOS:000338768100026 PM 24771347 ER PT J AU Hoskins, JW Ofori, LO Chen, CZ Kumar, A Sobczak, K Nakamori, M Southall, N Patnaik, S Marugan, JJ Zheng, W Austin, CP Disney, MD Miller, BL Thornton, CA AF Hoskins, Jason W. Ofori, Leslie O. Chen, Catherine Z. Kumar, Amit Sobczak, Krzysztof Nakamori, Masayuki Southall, Noel Patnaik, Samarjit Marugan, Juan J. Zheng, Wei Austin, Christopher P. Disney, Matthew D. Miller, Benjamin L. Thornton, Charles A. TI Lomofungin and dilomofungin: inhibitors of MBNL1-CUG RNA binding with distinct cellular effects SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MYOTONIC-DYSTROPHY TYPE-1; NEAREST-NEIGHBOR THERMODYNAMICS; EXPANDED CUG REPEAT; SMALL MOLECULES; MUSCLEBLIND PROTEINS; HEXANUCLEOTIDE REPEAT; MEDIATED NEURODEGENERATION; TRINUCLEOTIDE REPEAT; SPLICING DEFECTS; RATIONAL DESIGN AB Myotonic dystrophy type 1 (DM1) is a dominantly inherited neuromuscular disorder resulting from expression of RNA containing an expanded CUG repeat (CUG(exp)). The pathogenic RNA is retained in nuclear foci. Poly-(CUG) binding proteins in the Muscleblind-like (MBNL) family are sequestered in foci, causing misregulated alternative splicing of specific pre-mRNAs. Inhibitors of MBNL1-CUG(exp) binding have been shown to restore splicing regulation and correct phenotypes in DM1 models. We therefore conducted a high-throughput screen to identify novel inhibitors of MBNL1-(CUG)(12) binding. The most active compound was lomofungin, a natural antimicrobial agent. We found that lomofungin undergoes spontaneous dimerization in DMSO, producing dilomofungin, whose inhibition of MBNL1-(CUG)(12) binding was 17-fold more potent than lomofungin itself. However, while dilomofungin displayed the desired binding characteristics in vitro, when applied to cells it produced a large increase of CUG(exp) RNA in nuclear foci, owing to reduced turnover of the CUG(exp) transcript. By comparison, the monomer did not induce CUG(exp) accumulation in cells and was more effective at rescuing a CUG(exp)-induced splicing defect. These results support the feasibility of high-throughput screens to identify compounds targeting toxic RNA, but also demonstrate that ligands for repetitive sequences may have unexpected effects on RNA decay. C1 [Hoskins, Jason W.; Sobczak, Krzysztof; Nakamori, Masayuki; Thornton, Charles A.] Univ Rochester, Dept Neurol, Rochester, NY 14642 USA. [Ofori, Leslie O.] Univ Rochester, Dept Chem, Rochester, NY 14642 USA. [Chen, Catherine Z.; Southall, Noel; Patnaik, Samarjit; Marugan, Juan J.; Zheng, Wei; Austin, Christopher P.] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Kumar, Amit; Disney, Matthew D.] Scripps Florida, Dept Chem, Jupiter, FL 33458 USA. [Miller, Benjamin L.] Univ Rochester, Dept Dermatol, Rochester, NY 14642 USA. RP Thornton, CA (reprint author), Univ Rochester, Dept Neurol, Rochester, NY 14642 USA. EM Charles_thornton@urmc.rochester.edu RI Southall, Noel/H-8991-2012; OI Southall, Noel/0000-0003-4500-880X; Miller, Benjamin/0000-0003-1647-0122; Hoskins, Jason/0000-0001-6944-1996; Zheng, Wei/0000-0003-1034-0757 FU University of Rochester Wellstone Muscular Dystrophy Cooperative Research Center [U54NS048843]; Marigold Foundation; National Center for Advancing Translational Sciences; National Institutes of Health [AR049077, N2058345, 5R21NS071023, 1R01GM100788, 1R01GM079235] FX University of Rochester Wellstone Muscular Dystrophy Cooperative Research Center [U54NS048843]; Marigold Foundation postdoctoral fellowship (to C.Z.C.); Intramural Research Programs of the National Center for Advancing Translational Sciences; National Institutes of Health [AR049077, N2058345, 5R21NS071023 to B. L. M., 1R01GM100788 to B. L. M. and 1R01GM079235 to M. D. D.]. Source of open access funding: National Institutes of Health and institutional funds. NR 70 TC 12 Z9 12 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 10 BP 6591 EP 6602 DI 10.1093/nar/gku275 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AK9SW UT WOS:000338768100046 PM 24799433 ER PT J AU Shabalina, SA Ogurtsov, AY Spiridonov, NA Koonin, EV AF Shabalina, Svetlana A. Ogurtsov, Aleksey Y. Spiridonov, Nikolay A. Koonin, Eugene V. TI Evolution at protein ends: major contribution of alternative transcription initiation and termination to the transcriptome and proteome diversity in mammals SO NUCLEIC ACIDS RESEARCH LA English DT Article ID INTRINSICALLY DISORDERED REGIONS; EUKARYOTIC MESSENGER-RNAS; GENOME BROWSER DATABASE; SPLICE-SITE CHOICE; SELECTION PRESSURE; UNTRANSLATED REGIONS; FUNCTIONAL DIVERSITY; INTERACTION NETWORKS; SECONDARY STRUCTURE; INTERGENIC REGIONS AB Alternative splicing (AS), alternative transcription initiation (ATI) and alternative transcription termination (ATT) create the extraordinary complexity of transcriptomes and make key contributions to the structural and functional diversity of mammalian proteomes. Analysis of mammalian genomic and transcriptomic data shows that contrary to the traditional view, the joint contribution of ATI and ATT to the transcriptome and proteome diversity is quantitatively greater than the contribution of AS. Although the mean numbers of protein-coding constitutive and alternative nucleotides in gene loci are nearly identical, their distribution along the transcripts is highly non-uniform. On average, coding exons in the variable 5' and 3' transcript ends that are created by ATI and ATT contain approximately four times more alternative nucleotides than core protein-coding regions that diversify exclusively via AS. Short upstream exons that encompass alternative 5'-untranslated regions and N-termini of proteins evolve under strong nucleotide-level selection whereas in 3'-terminal exons that encode protein C-termini, protein-level selection is significantly stronger. The groups of genes that are subject to ATI and ATT show major differences in biological roles, expression and selection patterns. C1 [Shabalina, Svetlana A.; Ogurtsov, Aleksey Y.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20984 USA. [Spiridonov, Nikolay A.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20984 USA. EM shabalin@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov FU Department of Health and Human Services (DHHS) (National Institutes of Health, National Library of Medicine) FX Department of Health and Human Services (DHHS) (National Institutes of Health, National Library of Medicine) intramural funds. Funding for open access charge: DHHS (National Institutes of Health, National Library of Medicine) intramural funds. NR 78 TC 11 Z9 11 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 11 BP 7132 EP 7144 DI 10.1093/nar/gku342 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AK9TG UT WOS:000338769400035 PM 24792168 ER PT J AU Wang, W Naiyer, N Mitra, M Li, JL Williams, MC Rouzina, I Gorelick, RJ Wu, ZR Musier-Forsyth, K AF Wang, Wei Naiyer, Nada Mitra, Mithun Li, Jialin Williams, Mark C. Rouzina, Ioulia Gorelick, Robert J. Wu, Zhengrong Musier-Forsyth, Karin TI Distinct nucleic acid interaction properties of HIV-1 nucleocapsid protein precursor NCp15 explain reduced viral infectivity SO NUCLEIC ACIDS RESEARCH LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; GENOMIC RNA DIMERIZATION; COMPETITIVE ELECTROSTATIC BINDING; INTEGRATION IN-VITRO; DOUBLE-STRANDED DNA; T4 GENE-32 PROTEIN; REVERSE TRANSCRIPTION; CHAPERONE ACTIVITY; ZINC-FINGER; GAG POLYPROTEIN AB During human immunodeficiency virus type 1 (HIV-1) maturation, three different forms of nucleocapsid (NC) protein-NCp15 (p9 + p6), NCp9 (p7 + SP2) and NCp7-appear successively. A mutant virus expressing NCp15 shows greatly reduced infectivity. Mature NCp7 is a chaperone protein that facilitates remodeling of nucleic acids (NAs) during reverse transcription. To understand the strict requirement for NCp15 processing, we compared the chaperone function of the three forms of NC. NCp15 anneals tRNA to the primer-binding site at a similar rate as NCp7, whereas NCp9 is the most efficient annealing protein. Assays to measure NA destabilization show a similar trend. Dynamic light scattering studies reveal that NCp15 forms much smaller aggregates relative to those formed by NCp7 and NCp9. Nuclear magnetic resonance studies suggest that the acidic p6 domain of HIV-1 NCp15 folds back and interacts with the basic zinc fingers. Neutralizing the acidic residues in p6 improves the annealing and aggregation activity of NCp15 to the level of NCp9 and increases the protein-NA aggregate size. Slower NCp15 dissociation kinetics is observed by single-molecule DNA stretching, consistent with the formation of electrostatic inter-protein contacts, which likely contribute to the distinct aggregate morphology, irregular HIV-1 core formation and non-infectious virus. C1 [Wang, Wei; Naiyer, Nada; Mitra, Mithun; Wu, Zhengrong; Musier-Forsyth, Karin] Ohio State Univ, Ctr Retrovirus Res, Dept Chem & Biochem, Columbus, OH 43210 USA. [Wang, Wei; Naiyer, Nada; Mitra, Mithun; Wu, Zhengrong; Musier-Forsyth, Karin] Ohio State Univ, Ctr RNA Biol, Columbus, OH 43210 USA. [Li, Jialin; Williams, Mark C.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Rouzina, Ioulia] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. [Gorelick, Robert J.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD 21702 USA. RP Musier-Forsyth, K (reprint author), Ohio State Univ, Ctr Retrovirus Res, Dept Chem & Biochem, Columbus, OH 43210 USA. EM musier@chemistry.ohio-state.edu RI Mitra, Mithun/A-2133-2015; OI Williams, Mark C./0000-0003-3219-376X FU National Institutes of Health (NIH) [GM065056, GM072462]; National Science Foundation [MCB-1243883]; National Cancer Institute, NIH, Leidos Biomedical Research, Inc. [HHSN261200800001E] FX National Institutes of Health (NIH) [GM065056 to K.M.-F., GM072462 to M. C. W.]; National Science Foundation [MCB-1243883 to M. C. W.]; National Cancer Institute, NIH, Leidos Biomedical Research, Inc. [HHSN261200800001E to R.J.G., in part]. Funding for open access charge: NIH GM065056. NR 120 TC 11 Z9 11 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 11 BP 7145 EP 7159 DI 10.1093/nar/gku335 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AK9TG UT WOS:000338769400036 PM 24813443 ER PT B AU Seeff, LB Ghany, MG AF Seeff, Leonard B. Ghany, Marc G. BE Thompson, G TI HARVEY ALTER AND MICHAEL HOUGHTON: THE DISCOVERY OF HEPATITIS C AND THE INTRODUCTION OF SCREENING TO PREVENT ITS TRANSMISSION IN TRANSFUSED BLOOD SO PIONEERS OF MEDICINE WITHOUT A NOBEL PRIZE LA English DT Article; Book Chapter ID NON-B-HEPATITIS; NON-A-HEPATITIS; UNITED-STATES; POSTTRANSFUSION HEPATITIS; AUSTRALIA ANTIGEN; NATURAL-HISTORY; VIRUS; JAUNDICE; SEQUENCE; ANTIBODY C1 [Seeff, Leonard B.] Hill Grp, Bethesda, MD 20817 USA. [Seeff, Leonard B.] US FDA, Silver Spring, MD USA. [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. RP Seeff, LB (reprint author), Hill Grp, Bethesda, MD 20817 USA. NR 39 TC 0 Z9 0 U1 1 U2 2 PU IMPERIAL COLL PRESS PI COVENT GARDEN PA 57 SHELTON STREET, COVENT GARDEN WC2H 9HE, ENGLAND BN 978-1-78326-384-4; 978-1-78326-385-1; 978-1-78326-383-7 PY 2014 BP 197 EP 214 D2 10.1142/p922 PG 18 WC History & Philosophy Of Science SC History & Philosophy of Science GA BA6ZY UT WOS:000337341800014 ER PT J AU Federhen, S Clark, K Barrett, T Parkinson, H Ostell, J Kodama, Y Mashima, J Nakamura, Y Cochrane, G Karsch-Mizrachi, I AF Federhen, Scott Clark, Karen Barrett, Tanya Parkinson, Helen Ostell, James Kodama, Yuichi Mashima, Jun Nakamura, Yasukazu Cochrane, Guy Karsch-Mizrachi, Ilene TI Toward richer metadata for microbial sequences: replacing strain-level NCBI taxonomy taxids with BioProject, BioSample and Assembly records SO STANDARDS IN GENOMIC SCIENCES LA English DT Article ID DATABASE; GENOMICS; ARCHIVE; UPDATE AB Microbial genome sequence submissions to the International Nucleotide Sequence Database Collaboration (INSDC) have been annotated with organism names that include the strain identifier. Each of these strain-level names has been assigned a unique 'taxid' in the NCBI Taxonomy Database. With the significant growth in genome sequencing, it is not possible to continue with the curation of strain-level taxids. In January 2014, NCBI will cease assigning strain-level taxids. Instead, submitters are encouraged provide strain information and rich metadata with their submission to the sequence database, BioProject and BioSample. Copyright (C) retained by original authors C1 [Federhen, Scott; Clark, Karen; Barrett, Tanya; Ostell, James; Karsch-Mizrachi, Ilene] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Parkinson, Helen; Cochrane, Guy] European Bioinformat Inst, European Mol Biol Lab, Hinxton, England. [Kodama, Yuichi; Mashima, Jun; Nakamura, Yasukazu] Res Org Informat & Syst, Natl Inst Genet, DDBJ Ctr, Mishima, Shizuoka 4118540, Japan. RP Federhen, S (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. OI Parkinson, Helen/0000-0003-3035-4195; Cochrane, Guy/0000-0001-7954-7057 FU NIH, National Library of Medicine; European Molecular Biology Laboratory; Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) FX This work was supported in part by the Intramural Research Program of the NIH, National Library of Medicine, the European Molecular Biology Laboratory, and the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT). NR 14 TC 11 Z9 11 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1944-3277 J9 STAND GENOMIC SCI JI Stand. Genomic Sci. PY 2014 VL 9 IS 3 DI 10.4056/sigs.4851102 PG 5 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA AL2ZQ UT WOS:000338995000049 PM 25197497 ER PT J AU Waltemath, D Bergmann, FT Chaouiya, C Czauderna, T Gleeson, P Goble, C Golebiewski, M Hucka, M Juty, N Krebs, O Le Novere, N Mi, HY Moraru, II Myers, CJ Nickerson, D Olivier, BG Rodriguez, N Schreiber, F Smith, L Zhang, FK Bonnet, E AF Waltemath, Dagmar Bergmann, Frank T. Chaouiya, Claudine Czauderna, Tobias Gleeson, Padraig Goble, Carole Golebiewski, Martin Hucka, Michael Juty, Nick Krebs, Olga Le Novere, Nicolas Mi, Huaiyu Moraru, Ion I. Myers, Chris J. Nickerson, David Olivier, Brett G. Rodriguez, Nicolas Schreiber, Falk Smith, Lucian Zhang, Fengkai Bonnet, Eric TI Meeting report from the fourth meeting of the Computational Modeling in Biology Network (COMBINE) SO STANDARDS IN GENOMIC SCIENCES LA English DT Article ID SYSTEMS BIOLOGY; MARKUP LANGUAGE; SOFTWARE ENVIRONMENT; SIGNALING NETWORKS; SIMULATION; PATHWAY; CELL; DATABASE; MAPS; SBML AB The Computational Modeling in Biology Network (COMBINE) is an initiative to coordinate the development of community standards and formats in computational systems biology and related fields. This report summarizes the topics and activities of the fourth edition of the annual COMBINE meeting, held in Paris during September 16-20 2013, and attended by a total of 96 people. This edition pioneered a first day devoted to modeling approaches in biology, which attracted a broad audience of scientists thanks to a panel of renowned speakers. During subsequent days, discussions were held on many subjects including the introduction of new features in the various COMBINE standards, new software tools that use the standards, and outreach efforts. Significant emphasis went into work on extensions of the SBML format, and also into community-building. This year's edition once again demonstrated that the COMBINE community is thriving, and still manages to help coordinate activities between different standards in computational systems biology. Copyright (C) retained by original authors C1 [Waltemath, Dagmar] Univ Rostock, Dept Syst Biol & Bioinformat, D-18055 Rostock, Germany. [Bergmann, Frank T.; Hucka, Michael; Smith, Lucian] CALTECH, Dept Comp & Math Sci, Pasadena, CA 91125 USA. [Czauderna, Tobias; Schreiber, Falk] IPK Gatersleben, Gatersleben, Germany. [Chaouiya, Claudine] IGC, Oeiras, Portugal. [Gleeson, Padraig] UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6BT, England. [Goble, Carole] Univ Manchester, Sch Comp Sci, Manchester, Lancs, England. [Golebiewski, Martin; Krebs, Olga] Heidelberg Inst Theoret Studies, Heidelberg, Germany. [Juty, Nick; Le Novere, Nicolas] EMBL European Bioinformat Inst, Cambridge, England. [Mi, Huaiyu] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Moraru, Ion I.] Univ Connecticut, Ctr Hlth, Ctr Cell Anal & Modeling, Farmington, CT USA. [Myers, Chris J.] Univ Utah, Dept Elect & Comp Engn, Salt Lake City, UT 84112 USA. [Nickerson, David] Univ Auckland, Auckland Bioengn Inst, Auckland 1, New Zealand. [Olivier, Brett G.] Vrije Univ Amsterdam, Amsterdam, Netherlands. [Le Novere, Nicolas; Rodriguez, Nicolas] Babraham Inst, Cambridge, England. [Schreiber, Falk] Univ Halle Wittenberg, D-06108 Halle, Germany. [Schreiber, Falk] Monash Univ, Melbourne, Vic 3004, Australia. [Zhang, Fengkai] NIAID, Computat Biol Unit, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Bonnet, Eric] Inst Curie, Paris, France. [Bonnet, Eric] INSERM, U900, F-75248 Paris, France. [Bonnet, Eric] Mines ParisTech, F-77300 Fontainebleau, France. RP Waltemath, D (reprint author), Univ Rostock, Dept Syst Biol & Bioinformat, D-18055 Rostock, Germany. EM dagmar.waltemath@uni-rostock.de; eric.bonnet@curie.fr RI Chaouiya, Claudine/F-8560-2012; Gleeson, Padraig/A-7549-2012; OI Chaouiya, Claudine/0000-0003-2350-0756; Gleeson, Padraig/0000-0001-5963-8576; Bergmann, Frank/0000-0001-5553-4702 FU Foundation Pierre-Gilles de Gennes; Institut des Systemes Complexes; Groupement de Recherches en Bioinformatique Moleculaire du CNRS; NIAID, NIH FX The authors wish to thank all the workshop participants. COMBINE 2013 was supported by the Foundation Pierre-Gilles de Gennes, the Institut des Systemes Complexes and the Groupement de Recherches en Bioinformatique Moleculaire du CNRS. Fengkai Zhang was supported by the intramural program of NIAID, NIH. NR 65 TC 3 Z9 3 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1944-3277 J9 STAND GENOMIC SCI JI Stand. Genomic Sci. PY 2014 VL 9 IS 3 DI 10.4056/sigs.5279417 PG 23 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA AL2ZQ UT WOS:000338995000027 ER PT J AU Mehoudar, E Arizpe, J Baker, CI Yovel, G AF Mehoudar, Eyal Arizpe, Joseph Baker, Chris I. Yovel, Galit TI Faces in the eye of the beholder: Unique and stable eye scanning patterns of individual observers SO JOURNAL OF VISION LA English DT Article DE eye movements; face processing; individual differences ID MOVEMENTS; INFORMATION; RECOGNITION; PERCEPTION; TASK; IDENTIFICATION; PROSOPAGNOSIA; FIXATION; IDENTITY; CULTURE AB Eye scanning patterns while viewing pictures have provided valuable information in many domains of visual cognition. Such patterns are determined by the type of image viewed (e. g., faces, scenes) as well as the task individuals are asked to perform (e. g., visual search, memory). Here we show that another key factor that significantly influences eye scanning patterns but has been mostly overlooked is the individual observer. During face viewing, we found that individuals showed diverse scanning patterns that, in many cases, were inconsistent with the typical triangular shape pattern that is commonly observed when eye scanning patterns are averaged across individuals. These idiosyncratic eye scanning patterns were not random but highly stable even when examined 18 months later. Interestingly, these eye-tracking patterns were not predictive of behavioral performance. Such stable and unique scanning patterns may represent a specific behavioral trait/signature and be formed early in development, reflecting idiosyncratic strategies for performing visual recognition tasks. C1 [Mehoudar, Eyal; Yovel, Galit] Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel. [Arizpe, Joseph; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Arizpe, Joseph] UCL, Inst Cognit Neurosci, Lab Appl Cognit Neurosci, London, England. [Yovel, Galit] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel. RP Yovel, G (reprint author), Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel. EM gality@post.tau.ac.il RI Arizpe, Joseph/N-1399-2014; OI Arizpe, Joseph/0000-0001-8958-7757; Baker, Chris/0000-0001-6861-8964 FU binational science foundation (BSF); National Institute of Mental Health FX This work was supported by a binational science foundation (BSF) grant to G. Y. and C. I. B. C. I. B. and J. A. are supported by the Intramural Research Program of the National Institute of Mental Health. Author contributions: E. M. collected data, performed data analysis, and wrote the paper; J. A. collected data and performed data analysis; C. I. B. designed the study and wrote the paper; G. Y. designed the study and wrote the paper. NR 39 TC 8 Z9 8 U1 2 U2 17 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2014 VL 14 IS 7 AR 6 DI 10.1167/14.7.6 PG 11 WC Ophthalmology SC Ophthalmology GA AL0VK UT WOS:000338844900007 PM 25057839 ER PT S AU Allen, D Lu, L Yao, JH Liu, JM Turkbey, E Summers, RM AF Allen, David Lu, Le Yao, Jianhua Liu, Jiamin Turkbey, Evrim Summers, Ronald M. BE Ourselin, S Styner, MA TI Robust Automated Lymph Node Segmentation with Random Forests SO MEDICAL IMAGING 2014: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 16-18, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN, Inc, Ventana Med Syst Inc, Intrace Med DE Lymph node detection; machine learning; random forest ID CT IMAGES; RECOGNITION; TREES AB Enlarged lymph nodes may indicate the presence of illness. Therefore, identification and measurement of lymph nodes provide essential biomarkers for diagnosing disease. Accurate automatic detection and measurement of lymph nodes can assist radiologists for better repeatability and quality assurance, but is challenging as well because lymph nodes are often very small and have a highly variable shape. In this paper, we propose to tackle this problem via supervised statistical learning-based robust voxel labeling, specifically the random forest algorithm. Random forest employs an ensemble of decision trees that are trained on labeled multi-class data to recognize the data features and is adopted to handle low-level image features sampled and extracted from 3D medical scans. Here we exploit three types of image features (intensity, order-1 contrast and order-2 contrast) and evaluate their effectiveness in random forest feature selection setting. The trained forest can then be applied to unseen data by voxel scanning via sliding windows (11x11x11), to assign the class label and class-conditional probability to each unlabeled voxel at the center of window. Voxels from the manually annotated lymph nodes in a CT volume are treated as positive class; background non-lymph node voxels as negatives. We show that the random forest algorithm can be adapted and perform the voxel labeling task accurately and efficiently. The experimental results are very promising, with AUCs (area under curve) of the training and validation ROC (receiver operating characteristic) of 0.972 and 0.959, respectively. The visualized voxel labeling results also confirm the validity. C1 [Allen, David; Lu, Le; Yao, Jianhua; Liu, Jiamin; Turkbey, Evrim; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Allen, D (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. NR 20 TC 0 Z9 0 U1 1 U2 6 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9827-4 J9 PROC SPIE PY 2014 VL 9034 AR 90343X DI 10.1117/12.2043926 PG 8 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BA8RZ UT WOS:000338543300135 ER PT S AU Liu, JF Yao, JH Wang, SJ Linguraru, MG Summers, RM AF Liu, Jianfei Yao, Jianhua Wang, Shijun Linguraru, Marius George Summers, Ronald M. BE Ourselin, S Styner, MA TI Locally Constrained Active Contour: A Region-Based Level Set for Ovarian Cancer Metastasis Segmentation SO MEDICAL IMAGING 2014: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 16-18, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN, Inc, Ventana Med Syst Inc, Intrace Med DE Ovarian Cancer Metastasis; Tumor Segmentation; Region-based Level Set; Localization ID CT; QUANTIFICATION AB Accurate segmentation of ovarian cancer metastases is clinically useful to evaluate tumor growth and determine follow-up treatment. We present a region-based level set algorithm with localization constraints to segment ovarian cancer metastases. Our approach is established on a representative region-based level set, Chan-Vese model, in which an active contour is driven by region competition. To reduce over-segmentation, we constrain the level set propagation within a narrow image band by embedding a dynamic localization function. The metastasis intensity prior is also estimated from image regions within the level set initialization. The localization function and intensity prior force the level set to stop at the desired metastasis boundaries. Our approach was validated on 19 ovarian cancer metastases with radiologist-labeled ground-truth on contrast-enhanced CT scans from 15 patients. The comparison between our algorithm and geodesic active contour indicated that the volume overlap was 75 +/- 10% vs. 56 +/- 6%, the Dice coefficient was 83 +/- 8% vs. 63 +/- 8%, and the average surface distance was 2.2 +/- 0.6mm vs. 4.4 +/- 0.9mm Experimental results demonstrated that our algorithm outperformed traditional level set algorithms. C1 [Liu, Jianfei; Yao, Jianhua; Wang, Shijun; Summers, Ronald M.] NIH, Ctr Clin, Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Linguraru, Marius George] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediatr Surg Innovat, Washington, DC 20010 USA. RP Liu, JF (reprint author), NIH, Ctr Clin, Radiol & Imaging Sci, Bethesda, MD 20892 USA. FU National Institutes of Health, Clinical Center FX This work was supported by the Intramural Research Program of the National Institutes of Health, Clinical Center. NR 18 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9827-4 J9 PROC SPIE PY 2014 VL 9034 AR UNSP 903404 DI 10.1117/12.2043712 PG 6 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BA8RZ UT WOS:000338543300003 ER PT S AU Mahfouz, A Ziats, MN Rennert, OM Lelieveldt, BPF Reinders, MJT AF Mahfouz, Ahmed Ziats, Mark N. Rennert, Owen M. Lelieveldt, Boudewijn P. F. Reinders, Marcel J. T. BE Ourselin, S Styner, MA TI Genomic connectivity networks based on the Brain Span atlas of the developing human brain SO MEDICAL IMAGING 2014: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 16-18, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN, Inc, Ventana Med Syst Inc, Intrace Med DE BrainSpan atlas; brain connectivity; neurodevelopment; autistic disorder; gene expression; genomic connectivity networks ID GENETICS AB The human brain comprises systems of networks that span the molecular, cellular, anatomic and functional levels. Molecular studies of the developing brain have focused on elucidating networks among gene products that may drive cellular brain development by functioning together in biological pathways. On the other hand, studies of the brain connectome attempt to determine how anatomically distinct brain regions are connected to each other, either anatomically (diffusion tensor imaging) or functionally (functional MRI and EEG), and how they change over development. A global examination of the relationship between gene expression and connectivity in the developing human brain is necessary to understand how the genetic signature of different brain regions instructs connections to other regions. Furthermore, analyzing the development of connectivity networks based on the spatio-temporal dynamics of gene expression provides a new insight into the effect of neurodevelopmental disease genes on brain networks. In this work, we construct connectivity networks between brain regions based on the similarity of their gene expression signature, termed "Genomic Connectivity Networks" (GCNs). Genomic connectivity networks were constructed using data from the Brain Span Transcriptional Atlas of the Developing Human Brain. Our goal was to understand how the genetic signatures of anatomically distinct brain regions relate to each other across development. We assessed the neurodevelopmental changes in connectivity patterns of brain regions when networks were constructed with genes implicated in the neurodevelopmental disorder autism (autism spectrum disorder; ASD). Using graph theory metrics to characterize the GCNs, we show that ASD-GCNs are relatively less connected later in development with the cerebellum showing a very distinct expression of ASD-associated genes compared to other brain regions. C1 [Mahfouz, Ahmed; Reinders, Marcel J. T.] Delft Univ Technol, Delft Bioinformat Lab, NL-2600 AA Delft, Netherlands. [Mahfouz, Ahmed; Lelieveldt, Boudewijn P. F.] Univ Leipzig, Med Ctr, Dept Radiol, Div Image Proc, D-04109 Leipzig, Germany. [Mahfouz, Ahmed; Lelieveldt, Boudewijn P. F.; Reinders, Marcel J. T.] Delft Univ Technol, Dept Intelligent Syst, NL-2600 AA Delft, Netherlands. [Ziats, Mark N.; Rennert, Owen M.] NIH, Natl Inst Child Health & Human Dev, Bethesda, MD USA. [Ziats, Mark N.] Univ Cambridge, Cambridge CB2 1TN, England. [Ziats, Mark N.] Baylor Coll Med, Houston, TX 77030 USA. RP Mahfouz, A (reprint author), Delft Univ Technol, Delft Bioinformat Lab, NL-2600 AA Delft, Netherlands. EM a.mahfouz@lumc.nl RI Lelieveldt, Boudewijn/B-6501-2008 OI Lelieveldt, Boudewijn/0000-0001-8269-7603 NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9827-4 J9 PROC SPIE PY 2014 VL 9034 AR UNSP 90344G DI 10.1117/12.2044384 PG 7 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BA8RZ UT WOS:000338543300154 ER PT S AU Razeto, M Mohr, B Arakita, K Schuijf, JD Fuchs, A Kuhl, JT Chen, MY Kofoed, KF AF Razeto, Marco Mohr, Brian Arakita, Kazumasa Schuijf, Joanne D. Fuchs, Andreas Kuhl, J. Tobias Chen, Marcus Y. Kofoed, Klaus F. BE Ourselin, S Styner, MA TI Accurate, Fully-Automated Registration of Coronary Arteries for Volumetric CT Digital Subtraction Angiography SO MEDICAL IMAGING 2014: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 16-18, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN, Inc, Ventana Med Syst Inc, Intrace Med DE registration; subtraction; CT; coronary; angiography; CCTA; CTDSA ID MASK BONE ELIMINATION; NONRIGID REGISTRATION; FEASIBILITY AB Diagnosis of coronary artery disease with Coronary Computed Tomography Angiography (CCTA) is complicated by the presence of significant calcification or stents. Volumetric CT Digital Subtraction Angiography (CTDSA) has recently been shown to be effective at overcoming these limitations. Precise registration of structures is essential as any misalignment can produce artifacts potentially inhibiting clinical interpretation of the data. The fully-automated registration method described in this paper addresses the problem by combining a dense deformation field with rigid-body transformations where calcifications/stents are present. The method contains non-rigid and rigid components. Non-rigid registration recovers the majority of motion artifacts and produces a dense deformation field valid over the entire scan domain. Discrete domains are identified in which rigid registrations very accurately align each calcification/stent. These rigid-body transformations are combined within the immediate area of the deformation field using a distance transform to minimize distortion of the surrounding tissue. A recent interim analysis of a clinical feasibility study evaluated reader confidence and diagnostic accuracy in conventional CCTA and CTDSA registered using this method. Conventional invasive coronary angiography was used as the reference. The study included 27 patients scanned with a second-generation 320-row CT detector in which 41 lesions were identified. Compared to conventional CCTA, CTDSA improved reader confidence in 13/36 (36%) of segments with severe calcification and 3/5 (60%) of segments with coronary stents. Also, the false positive rate of CTDSA was reduced compared to conventional CCTA from 18% (24/130) to 14% (19/130). C1 [Razeto, Marco; Mohr, Brian] Toshiba Med Visualizat Syst, Edinburgh, Midlothian, Scotland. [Arakita, Kazumasa] Toshiba Med Syst Corp, Otawara, Japan. [Schuijf, Joanne D.] Toshiba Med Syst Europe, Zoetermeer, Netherlands. [Fuchs, Andreas; Kuhl, J. Tobias; Kofoed, Klaus F.] Rigshospitalet, Copenhagen, Denmark. [Chen, Marcus Y.] Natl Inst Hlth, Bethesda, MD USA. RP Mohr, B (reprint author), Toshiba Med Visualizat Syst, Edinburgh, Midlothian, Scotland. EM bmohr@tmvse.com NR 19 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9827-4 J9 PROC SPIE PY 2014 VL 9034 AR UNSP 90343F DI 10.1117/12.2042775 PG 7 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BA8RZ UT WOS:000338543300117 ER PT S AU Roy, S He, Q Carass, A Jog, A Cuzzocreo, JL Reich, DS Prince, J Pham, D AF Roy, Snehashis He, Qing Carass, Aaron Jog, Amod Cuzzocreo, Jennifer L. Reich, Daniel S. Prince, Jerry Pham, Dzung BE Ourselin, S Styner, MA TI Example Based Lesion Segmentation SO MEDICAL IMAGING 2014: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 16-18, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN, Inc, Ventana Med Syst Inc, Intrace Med DE magnetic resonance imaging; MRI; lesion segmentation; MS; patches ID MULTIPLE-SCLEROSIS; IMAGES; MRI AB Automatic and accurate detection of white matter lesions is a significant step toward understanding the progression of many diseases, like Alzheimer's disease or multiple sclerosis. Multi-modal MR images are often used to segment T-2 white matter lesions that can represent regions of demyelination or ischemia, Sonic automated lesion segmentation methods describe the lesion intensities using generative models, and then classify the lesions with some combination of heuristics and cost minimization. in contrast, we propose a patch-based method, in which lesions are found using examples from an atlas containing multi-modal MR images and corresponding manual delineations of lesions. Patches from subject ME images are matched to patches from the atlas and lesion memberships are found based on patch similarity weights. We experiment on 43 subjects with MS, whose scans show various levels of lesion-load. We demonstrate significant improvement in Dice coefficient and total lesion volume compared to a state of the art model-based lesion segmentation method, indicating more accurate delineation of lesions. C1 [Roy, Snehashis; He, Qing; Pham, Dzung] Henry M Jackson Fdn Adv Mil Med, Ctr Neurosci & Regenerat Med, Bethesda, MD 20817 USA. [Carass, Aaron; Jog, Amod; Prince, Jerry] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Cuzzocreo, Jennifer L.] Johns Hopkins Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Reich, Daniel S.] Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Translat Neuroradiol Unit, Bethesda, MD 20824 USA. RP Roy, S (reprint author), Henry M Jackson Fdn Adv Mil Med, Ctr Neurosci & Regenerat Med, Bethesda, MD 20817 USA. EM snehashis.roy@nih.gov RI Reich, Daniel/E-5701-2010; OI Reich, Daniel/0000-0002-2628-4334; Carass, Aaron/0000-0003-4939-5085 FU (NINDS); NIH/NIBIB [1R01EB017743, 1R21EB012765] FX Send correspondence to Snehashis Roy E- mail: snehashis. roy@ nih. gov. The data were acquired under grants from the National MS Society and EMD Serono to Dr. Peter Calabresi. This research was supported in part by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NINDS) and NIH/NIBIB under grants 1R01EB017743 and 1R21EB012765. NR 20 TC 7 Z9 7 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9827-4 J9 PROC SPIE PY 2014 VL 9034 AR UNSP 90341Y DI 10.1117/12.2043917 PG 8 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BA8RZ UT WOS:000338543300068 ER PT S AU Ogawa, M Yamauchi, T Iwai, H Magata, Y Choyke, PL Kobayashi, H AF Ogawa, Mikako Yamauchi, Toyohiko Iwai, Hidenao Magata, Yasuhiro Choyke, Peter L. Kobayashi, Hisataka BE Kessel, DH Hasan, T TI Investigation of dynamic morphological changes of cancer cells during photoimmuno therapy (PIT) by low-coherence quantitative phase microscopy SO OPTICAL METHODS FOR TUMOR TREATMENT AND DETECTION: MECHANISMS AND TECHNIQUES IN PHOTODYNAMIC THERAPY XXIII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Methods for Tumor Treatment and Detection - Mechanisms and Techniques in Photodynamic Therapy XXIII CY FEB 01-03, 2014 CL San Francisco, CA SP SPIE DE photo-immunotherapy; PDT; IRDye700DX; antibody; low-coherence quantitative phase microscope ID NEAR-INFRARED PHOTOIMMUNOTHERAPY; PHOTODYNAMIC THERAPY; DEATH; APOPTOSIS AB We have reported a new molecular-targeted cancer phototherapy, photoimmunotherapy (PIT), which killed implanted tumors in mice without side-effects. To understand the mechanism of cell killing with PIT, three-dimentional dynamic low-coherence quantitative phase microscopy (3D LC-QPM), a device developed by Hamamatsu Photonics K. K, was used to detect morphologic changes in cancer cells during PIT. 3T3/HER2 cells were incubated with anti-HER2 trastuzumab-IR700 (10 mu g/mL, 0.1 mu M as IR700) for 24 hours, then, three-dimensionally imaged with the LC-QPM during the exposure of two different optically filtered lights for excitation of IR700 (500-780 nm) and imaging (780-950 nm). For comparison with traditional PDT, the same experiments were performed with Photofrin (10 and 1 mu M). Serial changes in the cell membrane were readily visualized on 3D LC-QPM. 3T3/HER2 cells began to swell rapidly after exposure to 500-780 nm light excitation. The cell volume reached a maximum within 1 min after continuous exposure, and then the cells appeared to burst. This finding suggests that PIT damages the cell membrane by photo-reaction inducing an influx of water into the cell causing swelling and bursting of the cells. Interestingly, even after only 5 seconds of light exposure, the cells demonstrated swelling and bursting albeit more slowly, implying that sufficient cumulative damage occurs on the cell membrane to induce lethal damage to cells even at minimal light exposure. Similar but non-selective membrane damage was shown in PDT-treated cells Photofrin. Thus, PIT induces sufficient damage to the cell membrane within 5 seconds to induce rapid necrotic cell death which can be observed directly with 3D LC-QPM. Further investigation is needed to evaluate the biochemical mechanisms underlying PIT-induced cellular membrane damage. C1 [Ogawa, Mikako; Magata, Yasuhiro] Hamamatsu Univ Sch Med, Med Photon Res Ctr, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan. [Yamauchi, Toyohiko; Iwai, Hidenao] Hamamatsu Photon K K, Central Res Lab, Higashi Ku, Hamamatsu, Shizuoka 4348601, Japan. [Choyke, Peter L.; Kobayashi, Hisataka] NIH, NCI, Ctr Canc Res, Mol Imaging Program, Bethesda, MD 20892 USA. RP Ogawa, M (reprint author), Hamamatsu Univ Sch Med, Med Photon Res Ctr, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan. NR 10 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9844-1 J9 PROC SPIE PY 2014 VL 8931 AR UNSP 893113 DI 10.1117/12.2036944 PG 10 WC Oncology; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA8OF UT WOS:000338336500016 ER PT J AU Garimella, SV Gehlhaus, K Dine, JL Pitt, JJ Grandin, M Chakka, S Nau, MM Caplen, NJ Lipkowitz, S AF Garimella, Sireesha V. Gehlhaus, Kristie Dine, Jennifer L. Pitt, Jason J. Grandin, Magdalena Chakka, Sirisha Nau, Marion M. Caplen, Natasha J. Lipkowitz, Stanley TI Identification of novel molecular regulators of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in breast cancer cells by RNAi screening SO BREAST CANCER RESEARCH LA English DT Article ID TRAIL-INDUCED APOPTOSIS; NF-KAPPA-B; TYROSINE KINASE INHIBITOR; DRUG-INDUCED APOPTOSIS; MEDIATED APOPTOSIS; DOWN-REGULATION; UP-REGULATION; MONOCLONAL-ANTIBODY; LYMPHOID-CELLS; LUNG-CANCER AB Introduction: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) binds to its receptors, TRAIL-receptor 1 (TRAIL-R1) and TRAIL-receptor 2 (TRAIL-R2), leading to apoptosis by activation of caspase-8 and the downstream executioner caspases, caspase-3 and caspase-7 (caspase-3/7). Triple-negative breast cancer (TNBC) cell lines with a mesenchymal phenotype are sensitive to TRAIL, whereas other breast cancer cell lines are resistant. The underlying mechanisms that control TRAIL sensitivity in breast cancer cells are not well understood. Here, we performed small interfering RNA (siRNA) screens to identify molecular regulators of the TRAIL pathway in breast cancer cells. Methods: We conducted siRNA screens of the human kinome (691 genes), phosphatome (320 genes), and about 300 additional genes in the mesenchymal TNBC cell line MB231. Forty-eight hours after transfection of siRNA, parallel screens measuring caspase-8 activity, caspase-3/7 activity, or cell viability were conducted in the absence or presence of TRAIL for each siRNA, relative to a negative control siRNA (siNeg). A subset of genes was screened in cell lines representing epithelial TNBC (MB468), HER2-amplified breast cancer (SKBR3), and estrogen receptor-positive breast cancer (T47D). Selected putative negative regulators of the TRAIL pathway were studied by using small-molecule inhibitors. Results: The primary screens in MB231 identified 150 genes, including 83 kinases, 4 phosphatases, and 63 nonkinases, as potential negative regulators of TRAIL. The identified genes are involved in many critical cell processes, including apoptosis, growth factor-receptor signaling, cell-cycle regulation, transcriptional regulation, and DNA repair. Gene-network analysis identified four genes (PDPK1, IKBKB, SRC, and BCL2L1) that formed key nodes within the interaction network of negative regulators. A secondary screen of a subset of the genes identified in additional cell lines representing different breast cancer subtypes and sensitivities to TRAIL validated and extended these findings. Further, we confirmed that small-molecule inhibition of SRC or BCL2L1, in combination with TRAIL, sensitizes breast cancer cells to TRAIL-induced apoptosis, including cell lines resistant to TRAIL-induced cytotoxicity. Conclusions: These data identify novel molecular regulators of TRAIL-induced apoptosis in breast cancer cells and suggest strategies for the enhanced application of TRAIL as a therapy for breast cancer. C1 [Garimella, Sireesha V.; Dine, Jennifer L.; Nau, Marion M.; Lipkowitz, Stanley] Ctr Canc Res, Womens Maligancies Branch, Bethesda, MD 20892 USA. [Gehlhaus, Kristie; Pitt, Jason J.; Grandin, Magdalena; Chakka, Sirisha; Caplen, Natasha J.] Natl Canc Inst, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA. [Dine, Jennifer L.] Natl Inst Nursing Res, Bethesda, MD 20892 USA. [Garimella, Sireesha V.; Dine, Jennifer L.; Nau, Marion M.; Lipkowitz, Stanley] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Caplen, NJ (reprint author), Natl Canc Inst, Ctr Canc Res, Genet Branch, 37 Convent Dr, Bethesda, MD 20892 USA. EM ncaplen@mail.nih.gov; lipkowis@mail.nih.gov RI Caplen, Natasha/H-2768-2016 OI Caplen, Natasha/0000-0002-0001-9460 FU Intramural Research Program of the National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research. We thank Dr. Suntae Kim (Gene Silencing Section Genetics Branch, CCR, NCI, NIH) for help with Ingenuity Pathway Analysis, and Tamara L. Jones and Dr. Oliver Ou (Gene Silencing Section Genetics Branch, CCR, NCI, NIH) for technical assistance and discussion. NR 79 TC 5 Z9 5 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 2 AR R41 DI 10.1186/bcr3645 PG 21 WC Oncology SC Oncology GA AL2YF UT WOS:000338990900026 PM 24745479 ER PT J AU McMullin, RP Wittner, BS Yang, CW Denton-Schneider, BR Hicks, D Singavarapu, R Moulis, S Lee, J Akbari, MR Narod, SA Aldape, KD Steeg, PS Ramaswamy, S Sgroi, DC AF McMullin, Ryan P. Wittner, Ben S. Yang, Chuanwei Denton-Schneider, Benjamin R. Hicks, Daniel Singavarapu, Raj Moulis, Sharon Lee, Jeongeun Akbari, Mohammad R. Narod, Steven A. Aldape, Kenneth D. Steeg, Patricia S. Ramaswamy, Sridhar Sgroi, Dennis C. TI A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity SO BREAST CANCER RESEARCH LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; GENE-EXPRESSION; MUTATION CARRIERS; PARP INHIBITOR; 1ST RECURRENCE; TEMOZOLOMIDE; SURVIVAL; REPAIR; IMMUNOPHENOTYPE; TRASTUZUMAB AB Introduction: There is an unmet clinical need for biomarkers to identify breast cancer patients at an increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with human epidermal growth factor receptor 2-positive (HER2+) brain metastasis. Methods: We combined laser capture microdissection and gene expression microarrays to analyze malignant epithelium from HER2+ breast cancer brain metastases with that from HER2+ nonmetastatic primary tumors. Differential gene expression was performed including gene set enrichment analysis (GSEA) using publicly available breast cancer gene expression data sets. Results: In a cohort of HER2+ breast cancer brain metastases, we identified a gene expression signature that anti-correlates with overexpression of BRCA1. Sequence analysis of the HER2+ brain metastases revealed no pathogenic mutations of BRCA1, and therefore the aforementioned signature was designated BRCA1 Deficient-Like (BD-L). Evaluation of an independent cohort of breast cancer metastases demonstrated that BD-L values are significantly higher in brain metastases as compared to other metastatic sites. Although the BD-L signature is present in all subtypes of breast cancer, it is significantly higher in BRCA1 mutant primary tumors as compared with sporadic breast tumors. Additionally, BD-L signature values are significantly higher in HER2-/ER- primary tumors as compared with HER2+/ER+ and HER2-/ER+ tumors. The BD-L signature correlates with breast cancer cell line pharmacologic response to a combination of poly (ADP-ribose) polymerase (PARP) inhibitor and temozolomide, and the signature outperformed four published gene signatures of BRCA1/2 deficiency. Conclusions: A BD-L signature is enriched in HER2+ breast cancer brain metastases without pathogenic BRCA1 mutations. Unexpectedly, elevated BD-L values are found in a subset of primary tumors across all breast cancer subtypes. Evaluation of pharmacological sensitivity in breast cancer cell lines representing all breast cancer subtypes suggests the BD-L signature may serve as a biomarker to identify sporadic breast cancer patients who might benefit from a therapeutic combination of PARP inhibitor and temozolomide and may be indicative of a dysfunctional BRCA1-associated pathway. C1 [McMullin, Ryan P.; Yang, Chuanwei; Denton-Schneider, Benjamin R.; Hicks, Daniel; Singavarapu, Raj; Moulis, Sharon; Lee, Jeongeun; Sgroi, Dennis C.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [McMullin, Ryan P.; Wittner, Ben S.; Yang, Chuanwei; Moulis, Sharon; Lee, Jeongeun; Ramaswamy, Sridhar; Sgroi, Dennis C.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [McMullin, Ryan P.; Yang, Chuanwei; Moulis, Sharon; Lee, Jeongeun; Sgroi, Dennis C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Wittner, Ben S.; Ramaswamy, Sridhar] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Akbari, Mohammad R.; Narod, Steven A.] Womens Coll Hosp, Res Inst, Familial Breast Canc Res, Dept Neurosurg, Toronto, ON M5G 1N8, Canada. [Aldape, Kenneth D.] Texas Med Ctr, MD Anderson Canc Ctr, Houston, TX 77021 USA. [Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Sgroi, DC (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, 73 High St, Charlestown, MA 02129 USA. EM dsgroi@partners.org FU Department of Defense Breast Cancer Research Program Center of Excellence Grant [W81XW1T-06-2-0033]; Avon Foundation; Susan G. Komen for the Cure; NIH/National Cancer Institute FX Funding for the authors and project were provided through Department of Defense Breast Cancer Research Program Center of Excellence Grant W81XW1T-06-2-0033 (to DCS, PSS and KDA), the Avon Foundation (to DCS), the Susan G. Komen for the Cure (to DCS) and NIH/National Cancer Institute (to DCS). NR 49 TC 10 Z9 10 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 2 AR R25 DI 10.1186/bcr3625 PG 10 WC Oncology SC Oncology GA AL2YF UT WOS:000338990900010 PM 24625110 ER PT J AU Zhao, SS Chlebowski, RT Anderson, GL Kuller, LH Manson, JE Gass, M Patterson, R Rohan, TE Lane, DS Beresford, SAA Lavasani, S Rossouw, JE Prentice, RL AF Zhao, Shanshan Chlebowski, Rowan T. Anderson, Garnet L. Kuller, Lewis H. Manson, Joann E. Gass, Margery Patterson, Ruth Rohan, Thomas E. Lane, Dorothy S. Beresford, Shirley A. A. Lavasani, Sayeh Rossouw, Jacques E. Prentice, Ross L. TI Sex hormone associations with breast cancer risk and the mediation of randomized trial postmenopausal hormone therapy effects SO BREAST CANCER RESEARCH LA English DT Article ID ESTROGEN PLUS PROGESTIN; CONJUGATED EQUINE ESTROGENS; INITIATIVE CLINICAL-TRIAL; WOMEN; HYSTERECTOMY; MAMMOGRAPHY; MORTALITY AB Introduction: Paradoxically, a breast cancer risk reduction with conjugated equine estrogens (CEE) and a risk elevation with CEE plus medroxyprogesterone acetate (CEE + MPA) were observed in the Women's Health Initiative (WHI) randomized controlled trials. The effects of hormone therapy on serum sex hormone levels, and on the association between baseline sex hormones and disease risk, may help explain these divergent breast cancer findings. Methods: Serum sex hormone concentrations were measured for 348 breast cancer cases in the CEE + MPA trial and for 235 cases in the CEE trial along with corresponding pair-matched controls, nested within the WHI trials of healthy postmenopausal women. Association and mediation analyses, to examine the extent to which sex hormone levels and changes can explain the breast cancer findings, were conducted using logistic regression. Results: Following CEE treatment, breast cancer risk was associated with higher concentrations of baseline serum estrogens, and with lower concentrations of sex hormone binding globulin. However, following CEE + MPA, there was no association of breast cancer risk with baseline sex hormone levels. The sex hormone changes from baseline to year 1 provided an explanation for much of the reduced breast cancer risk with CEE. Specifically, the treatment odds ratio (95% confidence interval) increased from 0.71 (0.43, 1.15) to 0.92 (0.41, 2.09) when the year 1 measures were included in the logistic regression analysis. In comparison, the CEE + MPA odds ratio was essentially unchanged when these year 1 measures were included. Conclusions: Breast cancer risk remains low following CEE use among women having favorable baseline sex hormone profiles, but CEE + MPA evidently produces a breast cancer risk for all women similar to that for women having an unfavorable baseline sex hormone profile. These patterns could reflect breast ductal epithelial cell stimulation by CEE + MPA that is substantially avoided with CEE, in conjunction with relatively more favorable effects of either regimen following a sustained period of estrogen deprivation. These findings may have implications for other hormone therapy formulations and routes of delivery. C1 [Zhao, Shanshan; Anderson, Garnet L.; Prentice, Ross L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Chlebowski, Rowan T.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Kuller, Lewis H.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Manson, Joann E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. [Gass, Margery] Univ Cincinnati, Univ Hosp Menopause, Cincinnati, OH USA. [Gass, Margery] Univ Cincinnati, Osteoporosis Ctr, Cincinnati, OH USA. [Patterson, Ruth] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Lane, Dorothy S.] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. [Beresford, Shirley A. A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Lavasani, Sayeh] Karmanos Canc Ctr, Dept Oncol, Detroit, MI USA. [Rossouw, Jacques E.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Prentice, RL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave North,POB 19024, Seattle, WA 98109 USA. EM rprentic@whi.org OI Anderson, Garnet/0000-0001-5087-7837 FU National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; National Institutes of Health [P01 53996, R21 HL109527] FX This work was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services (contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C). Dr. Prentice's work was partially supported by the National Institutes of Health (grants P01 53996 and R21 HL109527). Decisions concerning study design, data collection and analysis, interpretation of the results, the preparation of the manuscript, or the decision to submit the manuscript for publication resided with committees comprised of WHI investigators that included NHLBI representatives. NR 22 TC 6 Z9 6 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2014 VL 16 IS 2 AR R30 DI 10.1186/bcr3632 PG 9 WC Oncology SC Oncology GA AL2YF UT WOS:000338990900015 PM 24670297 ER PT J AU Zhang, HL Zhang, YW Yasukawa, T Dalla Rosa, I Khiati, S Pommier, Y AF Zhang, Hongliang Zhang, Yong-Wei Yasukawa, Takehiro Dalla Rosa, Ilaria Khiati, Salim Pommier, Yves TI Increased negative supercoiling of mtDNA in TOP1mt knockout mice and presence of topoisomerases II alpha and II beta in vertebrate mitochondria SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA TOPOISOMERASES; MAMMALIAN MITOCHONDRIA; IB TOPOISOMERASES; GENOME; GENE; MAINTENANCE; RELAXATION; MECHANISM; CLEAVAGE; DRUGS AB Topoisomerases are critical for replication, DNA packing and repair, as well as for transcription by allowing changes in DNA topology. Cellular DNA is present both in nuclei and mitochondria, and mitochondrial topoisomerase I (Top1mt) is the only DNA topoisomerase specific for mitochondria in vertebrates. Here, we report in detail the generation of TOP1mt knockout mice, and demonstrate that mitochondrial DNA (mtDNA) displays increased negative supercoiling in TOP1mt knockout cells and murine tissues. This finding suggested imbalanced topoisomerase activity in the absence of Top1mt and the activity of other topoisomerases in mitochondria. Accordingly, we found that both Top2 alpha and Top2 beta are present and active in mouse and human mitochondria. The presence of Top2 alpha-DNA complexes in the mtDNA D-loop region, at the sites where both ends of 7S DNA are positioned, suggests a structural role for Top2 in addition to its classical topoisomerase activities. C1 [Zhang, Hongliang; Zhang, Yong-Wei; Dalla Rosa, Ilaria; Khiati, Salim; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Zhang, Hongliang; Zhang, Yong-Wei; Dalla Rosa, Ilaria; Khiati, Salim; Pommier, Yves] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Yasukawa, Takehiro] UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM hongliangzhang@mail.nih.gov; pommier@nih.gov FU NIH Intramural Program, Center for Cancer Research, National Cancer Institute [Z01 BC 006161]; Biotechnology and Biological Sciences Research Council (UK) FX NIH Intramural Program, Center for Cancer Research, National Cancer Institute [Z01 BC 006161]; Biotechnology and Biological Sciences Research Council (UK) David Phillips Fellowship (to T.Y.). Funding for open access charge: NIH Intramural Program, Center for Cancer Research, National Cancer Institute [Z01 BC 006161]. NR 52 TC 10 Z9 10 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 11 BP 7259 EP 7267 DI 10.1093/nar/gku384 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AK9TG UT WOS:000338769400045 PM 24803675 ER PT J AU Watts, M Fendler, B Merrins, MJ Satin, LS Bertram, R Sherman, A AF Watts, Margaret Fendler, Bernard Merrins, Matthew J. Satin, Leslie S. Bertram, Richard Sherman, Arthur TI Calcium and Metabolic Oscillations in Pancreatic Islets: Who's Driving the Bus? SO SIAM JOURNAL ON APPLIED DYNAMICAL SYSTEMS LA English DT Article DE oscillations; calcium; pancreatic beta-cells; dual oscillator model; metabolic ID PURINE NUCLEOTIDE CYCLE; CYTOPLASMIC FREE CA2+; BETA-CELLS; ELECTRICAL-ACTIVITY; INSULIN-SECRETION; ATP/ADP RATIO; GLYCOLYTIC OSCILLATIONS; OXYGEN-CONSUMPTION; MUSCLE EXTRACTS; BURSTING MODEL AB Pancreatic islets exhibit bursting oscillations in response to elevated blood glucose. These oscillations are accompanied by oscillations in the free cytosolic Ca2+ concentration (Ca-c), which drives pulses of insulin secretion. Both islet Ca2+ and metabolism oscillate, but there is some debate about their interrelationship. Recent experimental data show that metabolic oscillations in some cases persist after the addition of diazoxide (Dz), which opens K(ATP) channels, hyperpolarizing beta-cells and preventing Ca2+ entry and Ca2+ oscillations. Further, in some islets in which metabolic oscillations were eliminated with Dz, increasing the cytosolic Ca2+ concentration by the addition of KCl could restart the metabolic oscillations. Here we address why metabolic oscillations persist in some islets but not others, and why raising Cac restarts oscillations in some islets but not others. We answer these questions using the dual oscillator model (DOM) for pancreatic islets. The DOM can reproduce the experimental data and shows that the model supports two different mechanisms for slow metabolic oscillations, one that requires calcium oscillations and one that does not. C1 [Watts, Margaret; Sherman, Arthur] NIH, Bethesda, MD 20892 USA. [Fendler, Bernard] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Merrins, Matthew J.; Satin, Leslie S.] Univ Michigan, Ann Arbor, MI 48105 USA. [Bertram, Richard] Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. [Bertram, Richard] Florida State Univ, Program Neurosci, Tallahassee, FL 32306 USA. [Bertram, Richard] Florida State Univ, Program Mol Biophys, Tallahassee, FL 32306 USA. RP Watts, M (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM margaret.watts@nih.gov; bfendler@cshl.edu; mmerrins@umich.edu; lsatin@umich.edu; bertram@math.fsu.edu; asherman@nih.gov FU NIH/NIDDK Intramural Research Program; Simons Foundation; Starr Cancer Consortium [I3-A123]; National Institutes of Health [F32-DK085960, R01-DK46409, DK080714] FX National Institutes of Health, Bethesda, MD 20892 (margaret.watts@nih.gov, asherman@nih.gov). The first and sixth authors' research was supported by the NIH/NIDDK Intramural Research Program.; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724 (bfendler@cshl.edu). This author's research was supported by the Simons Foundation and the Starr Cancer Consortium (I3-A123).; University of Michigan, Ann Arbor, MI 48105 (mmerrins@umich.edu, lsatin@umich.edu). The third author's research was supported by the National Institutes of Health (F32-DK085960), and the fourth author's research was supported by the National Institutes of Health (R01-DK46409).; Department of Mathematics and Programs in Neuroscience and Molecular Biophysics, Florida State University, Tallahassee, FL 32306 (bertram@math.fsu.edu). This author's research was supported by the National Institutes of Health (DK080714). NR 60 TC 4 Z9 4 U1 0 U2 5 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 1536-0040 J9 SIAM J APPL DYN SYST JI SIAM J. Appl. Dyn. Syst. PY 2014 VL 13 IS 2 BP 683 EP 703 DI 10.1137/130920198 PG 21 WC Mathematics, Applied; Physics, Mathematical SC Mathematics; Physics GA AL0SA UT WOS:000338835800003 PM 25698909 ER PT J AU Jackson, SN Barbacci, D Egan, T Lewis, EK Schultz, JA Woods, AS AF Jackson, Shelley N. Barbacci, Damon Egan, Thomas Lewis, Ernest K. Schultz, J. Albert Woods, Amina S. TI MALDI-ion mobility mass spectrometry of lipids in negative ion mode SO ANALYTICAL METHODS LA English DT Article ID PHOSPHOLIPIDS; TOFMS; PHOSPHATIDYLCHOLINES; LOCALIZATION; LIPIDOMICS; SECTIONS; MS AB Profiling and imaging using MALDI mass spectrometry (MS) allows detection and localization of biomolecules in tissue, of which lipids are a major component. However, due to the in situ nature of this technique, complexity of tissue and need for a chemical matrix, the recorded signal is complex and can be difficult to assign. Ion mobility adds a dimension that provides coarse shape information, separating isobaric lipids, peptides, and oligonucleotides along distinct familial trend lines before mass analysis. Previous work using MALDI-ion mobility mass spectrometry to analyze and image lipids has been conducted mainly in positive ion mode, although several lipid classes ionize preferentially in negative ion mode. This work highlights recent data acquired in negative ion mode to detect glycerophosphoethanolamines (PEs), glycerophosphoserines (PSs), glycerophosphoglycerols (PGs), glycerolphosphoinositols (PIs), glycerophosphates (PAs), sulfatides (STs), and gangliosides from standard tissue extracts and directly from mouse brain tissue. In particular, this study focused on changes in ion mobility based upon lipid head groups, composition of radyl chain (# of carbons and double bonds), diacyl versus plasmalogen species, and hydroxylation of species. Finally, a MALDI-ion mobility imaging run was conducted in negative ion mode, resulting in the successful ion mapping of several lipid species. C1 [Jackson, Shelley N.; Barbacci, Damon; Woods, Amina S.] NIDA, IRP, NIH, Baltimore, MD 21224 USA. [Barbacci, Damon; Egan, Thomas; Lewis, Ernest K.; Schultz, J. Albert] Ionwerks Inc, Houston, TX USA. RP Woods, AS (reprint author), NIDA, IRP, NIH, Cassell Dr,Room 1120, Baltimore, MD 21224 USA. EM awoods@mail.nih.gov FU Intramural Research Program of the National Institute on Drug Abuse, NIH [5R44DA030853, 2R44DA036263-02]; NIH SBIR phase II [5R44DA030853, 2R44DA036263-02] FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, NIH. Ionwerks gratefully acknowledges partial support of this work from NIH SBIR phase II grants 5R44DA030853 and 2R44DA036263-02. NR 32 TC 15 Z9 15 U1 6 U2 30 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1759-9660 EI 1759-9679 J9 ANAL METHODS-UK JI Anal. Methods PY 2014 VL 6 IS 14 BP 5001 EP 5007 DI 10.1039/c4ay00320a PG 7 WC Chemistry, Analytical; Food Science & Technology; Spectroscopy SC Chemistry; Food Science & Technology; Spectroscopy GA AK5BJ UT WOS:000338438500010 PM 24999374 ER PT J AU Freed, WJ Chen, J Kindberg, A Bendriem, R Spivak, CE Lupica, C Lee, CT AF Freed, W. J. Chen, J. Kindberg, A. Bendriem, R. Spivak, C. E. Lupica, C. Lee, C. -T. TI In Vitro Models of the Human Neocortex Based on Pluripotent Stem Cells SO CELL TRANSPLANTATION LA English DT Meeting Abstract C1 [Freed, W. J.; Chen, J.; Kindberg, A.; Bendriem, R.; Spivak, C. E.; Lupica, C.; Lee, C. -T.] NIDA, Intramural Res Program, NIH, DHHS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2014 VL 23 IS 6 BP 770 EP 770 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA AK5RM UT WOS:000338484000035 ER PT J AU Kindberg, AA Lee, CT Bendriem, RM Williams, MP Harvey, BK Richie, CT Freed, WJ AF Kindberg, A. A. Lee, C. -T. Bendriem, R. M. Williams, M. P. Harvey, B. K. Richie, C. T. Freed, W. J. TI WNT3/WNT9B Signaling Orchestrates Human Pluripotent Stem Cell-Derived Mesodiencephalic Dopaminergic Neuron Differentiation SO CELL TRANSPLANTATION LA English DT Meeting Abstract C1 [Kindberg, A. A.; Lee, C. -T.; Bendriem, R. M.; Williams, M. P.; Freed, W. J.] NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD USA. [Harvey, B. K.; Richie, C. T.] NIDA, Optogenet & Transgen Technol Core, Intramural Res Program, NIH,DHHS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2014 VL 23 IS 6 BP 774 EP 774 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA AK5RM UT WOS:000338484000047 ER PT J AU Lee, CT Kindberg, AA Bendriem, RM Drgon, T Mallon, BS Uhl, GR Freed, WJ AF Lee, C. -T. Kindberg, A. A. Bendriem, R. M. Drgon, T. Mallon, B. S. Uhl, G. R. Freed, W. J. TI Identification of 17q21.31/WNT3-WNT9B Amplification Related to Accelerated Mesodiencephalic Dopaminergic Differentiation of Human Pluripotent Stem Cells SO CELL TRANSPLANTATION LA English DT Meeting Abstract C1 [Lee, C. -T.; Kindberg, A. A.; Bendriem, R. M.; Drgon, T.; Mallon, B. S.; Uhl, G. R.; Freed, W. J.] NIDA, Intramural Res Program, NIH, DHHS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2014 VL 23 IS 6 BP 776 EP 776 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA AK5RM UT WOS:000338484000051 ER PT J AU Horn, EJ Moore, HM AF Horn, Elizabeth J. Moore, Helen M. TI Overcoming challenges in the acquisition of biospecimens for rare diseases SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Editorial Material DE biorepositories; biospecimen science; confidentiality; rare disease ID GENE-EXPRESSION AB High-quality biospecimens are vital to furthering our understanding of human disease. Biospecimen collections for rare diseases pose unique challenges, and collaboration is often necessary for success. Several initiatives and tools have been developed to facilitate the collection of high-quality biospecimens and increase collaboration for biospecimen users. As science and technology advance, the research community must continue to develop tools and solutions to improve Biospecimen Science, advance research, and facilitate collaboration, while keeping pace with evolving scientific and ethical considerations. C1 [Horn, Elizabeth J.] LHC Biosolut, Portland, OR 97221 USA. [Moore, Helen M.] NCI, Biorepositories & Biospecimen Res Branch, Bethesda, MD 20892 USA. RP Moore, HM (reprint author), NCI, Biorepositories & Biospecimen Res Branch, 9609 Med Ctr Dr,MSC 9728, Bethesda, MD 20892 USA. EM moorehe@mail.nih.gov NR 17 TC 1 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PD JAN PY 2014 VL 2 IS 1 BP 1 EP 4 DI 10.1517/21678707.2014.859072 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AK2VV UT WOS:000338278600001 ER PT S AU Graper, ML Huster, D Kaler, SG Lutsenko, S Schilsky, ML Thiele, DJ AF Graper, Mary L. Huster, Dominik Kaler, Stephen G. Lutsenko, Svetlana Schilsky, Michael L. Thiele, Dennis J. GP New York Acad Sci TI Introduction to Human Disorders of Copper Metabolism SO HUMAN DISORDERS OF COPPER METABOLISM I SE Annals of the New York Academy of Sciences LA English DT Editorial Material CT International Workshop on Human Disorders of Copper Metabolism - Recent Advances and Main Challenges CY APR 08-09, 2013 CL Johns Hopkins Sch Med, Baltimore, MD SP Natl Inst Gen Med Sci, Wilson Dis Assoc HO Johns Hopkins Sch Med C1 [Graper, Mary L.] Wilson Dis Assoc, Milwaukee, WI 53217 USA. [Huster, Dominik] Deaconess Hosp, Leipzig, Germany. [Kaler, Stephen G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Lutsenko, Svetlana] Johns Hopkins Univ, Baltimore, MD USA. [Schilsky, Michael L.] Yale Univ, New Haven, CT USA. [Thiele, Dennis J.] Duke Univ, Sch Med, Durham, NC USA. RP Graper, ML (reprint author), Wilson Dis Assoc, Milwaukee, WI 53217 USA. NR 0 TC 3 Z9 3 U1 2 U2 6 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2014 VL 1314 BP V EP VI DI 10.1111/nyas.12448 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BA8PS UT WOS:000338448700002 PM 24820197 ER PT S AU Yi, L Kaler, S AF Yi, Ling Kaler, Stephen GP New York Acad Sci TI ATP7A trafficking and mechanisms underlying the distal motor neuropathy induced by mutations in ATP7A SO HUMAN DISORDERS OF COPPER METABOLISM I SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT International Workshop on Human Disorders of Copper Metabolism - Recent Advances and Main Challenges CY APR 08-09, 2013 CL Johns Hopkins Sch Med, Baltimore, MD SP Natl Inst Gen Med Sci, Wilson Dis Assoc HO Johns Hopkins Sch Med DE ATP7A; distal motor neuropathy; p97/VCP; adaptor protein complexes ID TRANS-GOLGI NETWORK; P-TYPE ATPASE; MENKES PROTEIN; REGULATED TRAFFICKING; PLASMA-MEMBRANE; COPPER ATPASE; DI-LEUCINE; DISEASE; LOCALIZATION; CLATHRIN AB Diverse mutations in the gene encoding the copper transporter ATP7A lead to X-linked recessive Menkes disease or occipital horn syndrome. Recently, two unique ATP7A missense mutations, T994I and P1386S, were shown to cause isolated adult-onset distal motor neuropathy. These mutations induce subtle defects in ATP7A intracellular trafficking resulting in preferential accumulation at the plasma membrane compared to wild-type ATP7A. Immunoprecipitation assays revealed abnormal interaction between ATP7A(T994I) and p97/VCP, a protein mutated in two autosomal dominant forms of motor neuron disease. Small-interfering RNA knockdown of valosin-containing protein corrected ATP7A(T994I) mislocalization. For ATP7A(P1386S), flow cytometry documented that nonpermeabilized fibroblasts bound a C-terminal ATP7A antibody, suggesting unstable insertion of the eighth transmembrane segment due to a helix-breaker effect of the amino acid substitution. This could sabotage interaction of ATP7A(P1386S) with adaptor protein complexes. These molecular events appear to selectively disturb normal motor neuron function and lead to neurologic illness that takes years and sometimes decades to develop. C1 [Yi, Ling; Kaler, Stephen] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Translat Neurosci, Program Mol Med, NIH, Bethesda, MD 20892 USA. RP Yi, L (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Translat Neurosci, Program Mol Med, NIH, Bldg 35,Room 2D-971,35 Convent Dr MSC 3754, Bethesda, MD 20892 USA. EM yil@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 25 TC 4 Z9 4 U1 0 U2 4 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2014 VL 1314 BP 49 EP 54 DI 10.1111/nyas.12427 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BA8PS UT WOS:000338448700009 PM 24754450 ER PT S AU Martinelli, D Dionisi-Vici, C AF Martinelli, Diego Dionisi-Vici, Carlo GP New York Acad Sci TI AP1S1 defect causing MEDNIK syndrome: a new adaptinopathy associated with defective copper metabolism SO HUMAN DISORDERS OF COPPER METABOLISM I SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT International Workshop on Human Disorders of Copper Metabolism - Recent Advances and Main Challenges CY APR 08-09, 2013 CL Johns Hopkins Sch Med, Baltimore, MD SP Natl Inst Gen Med Sci, Wilson Dis Assoc HO Johns Hopkins Sch Med DE AP1S1; adaptor protein complexes; MEDNIK syndrome; adaptinopathies ID LINKED MENTAL-RETARDATION; ADAPTER PROTEIN COMPLEXES; PUNCTATE PALMOPLANTAR KERATODERMA; CLATHRIN ADAPTER; BIOCHEMICAL-CHARACTERIZATION; SACCHAROMYCES-CEREVISIAE; INTELLECTUAL DISABILITY; SPASTIC PARAPLEGIA; SYNAPTIC VESICLES; DEFICIENCY CAUSES AB MEDNIK (mental retardation, enteropathy, deafness, neuropathy, ichthyosis, and keratodermia) syndrome has been recently described as a new disorder of copper metabolism. This multisystem disease combines clinical and biochemical signs of both Menkes and Wilson's diseases, in which liver copper overload is treatable using zinc acetate therapy. MEDNIK syndrome is caused by mutation of the AP1S1 gene, which codes for the sigma 1A subunit of adaptor protein complex 1, and directs intracellular trafficking of copper pumps ATP7A and ATP7B. Adaptor protein complexes regulate clathrin-coated vesicle assembly, protein cargo sorting, and vesicular trafficking between organelles in eukaryotic cells. A growing number of diseases have been associated with mutations in genes coding for adaptor protein complexes subunits and we propose for them the term adaptinopathies, as a new organic category of disorders of intracellular trafficking, which offers the opportunity to dissect the mechanisms involved in the crosstalk between the Golgi apparatus and the other organelles. C1 [Martinelli, Diego; Dionisi-Vici, Carlo] Bambino Gesu Pediat Hosp, Unit Metab, Dept Pediat, Rome, Italy. [Martinelli, Diego] NICHD, Sect Translat Neurosci, Program Mol Med, NIH, Bethesda, MD USA. RP Martinelli, D (reprint author), Bambino Gesu Pediat Hosp, IRCCS, Dept Pediat, Unit Metab, Piazza St Onofrio 4, Rome, Italy. EM diego.martinelli@opbg.net FU association La Vita e un Dono FX We thank the association La Vita e un Dono for supporting the fellowship of Dr. Diego Martinelli. NR 63 TC 6 Z9 6 U1 0 U2 4 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2014 VL 1314 BP 55 EP 63 DI 10.1111/nyas.12426 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BA8PS UT WOS:000338448700010 PM 24754424 ER PT S AU Kaler, SG AF Kaler, Stephen G. GP New York Acad Sci TI Translational research investigations on ATP7A: an important human copper ATPase SO HUMAN DISORDERS OF COPPER METABOLISM I SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT International Workshop on Human Disorders of Copper Metabolism - Recent Advances and Main Challenges CY APR 08-09, 2013 CL Johns Hopkins Sch Med, Baltimore, MD SP Natl Inst Gen Med Sci, Wilson Dis Assoc HO Johns Hopkins Sch Med DE ATP7A; Menkes disease; occipital horn syndrome; viral gene therapy; human copper metabolism ID DISTAL MOTOR NEUROPATHY; OCCIPITAL-HORN-SYNDROME; DISEASE MOUSE MODEL; MENKES-DISEASE; CANDIDATE GENE; RECESSIVE DISORDER; NEONATAL DIAGNOSIS; MUTATIONS; PLASMA; METABOLISM AB In more than 40 years since copper deficiency was delineated in pediatric subjects with Menkes disease, remarkable advances in our understanding of the clinical, biochemical, and molecular aspects of the human copper transporter ATP7A have emerged. Mutations in the gene encoding this multitasking molecule are now implicated in at least two other distinctive phenotypes: occipital horn syndrome and ATP7A-related isolated distal motor neuropathy. Several other novel inherited disorders of copper metabolism have been identified in the past several years, aided by advances in human gene mapping and automated DNA sequencing. In this paper, I review the history and evolution of our understanding of disorders caused by impaired ATP7A function, and outline future challenges. C1 [Kaler, Stephen G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Translat Neurosci, Program Mol Med, NIH, Bethesda, MD 20892 USA. RP Kaler, SG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Translat Neurosci, Program Mol Med, NIH,Porter Neurosci Res Ctr 2, Bldg 35,Room 2D-971,35 Convent Dr,MSC 3754, Bethesda, MD 20892 USA. EM kalers@mail.nih.gov FU Intramural NIH HHS [ZIA HD008768-10] NR 30 TC 7 Z9 7 U1 0 U2 3 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2014 VL 1314 BP 64 EP 68 DI 10.1111/nyas.12422 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BA8PS UT WOS:000338448700011 PM 24735419 ER PT J AU Davis, BW Ostrander, EA AF Davis, Brian W. Ostrander, Elaine A. TI Domestic Dogs and Cancer Research: A Breed-Based Genomics Approach SO ILAR JOURNAL LA English DT Article DE canine cancer; chip-seq; dog colony; exome; histiocytic sarcoma; osteosarcoma; RNA-seq; squamous cell carcinoma of the digit; transitional cell carcinoma; tumor sequencing; whole genome ID TRANSITIONAL-CELL CARCINOMA; CANINE PROSTATE CARCINOMA; HISTIOCYTIC SARCOMA; URINARY-BLADDER; INTRAEPITHELIAL NEOPLASIA; LINKAGE DISEQUILIBRIUM; COMPARATIVE BIOLOGY; SPONTANEOUS MODEL; UNITED-STATES; BREAST-CANCER AB Domestic dogs are unique from other animal models of cancer in that they generally experience spontaneous disease. In addition, most types of cancer observed in humans are found in dogs, suggesting that canines may be an informative system for the study of cancer genetics. Domestic dogs are divided into over 175 breeds, with members of each breed sharing significant phenotypes. The breed barrier enhances the utility of the model, especially for genetic studies where small numbers of genes are hypothesized to account for the breed cancer susceptibility. These facts, combined with recent advances in high-throughput sequencing technologies allows for an unrivaled ability to use pet dog populations to find often subtle mutations that promote cancer susceptibility and progression in dogs as a whole. The meticulous record keeping associated with dog breeding makes the model still more powerful, as it facilitates both association analysis and family-based linkage studies. Key to the success of these studies is their cooperative nature, with owners, scientists, veterinarians and breed clubs working together to avoid the cost and unpopularity of developing captive populations. In this article we explore these principals and advocate for colony-free, genetic studies that will enhance our ability to diagnose and treat cancer in dogs and humans alike. C1 [Davis, Brian W.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Ostrander, Elaine A.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Ostrander, EA (reprint author), NIH, Bldg 50,Room 5351,50 South Dr, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS NR 97 TC 13 Z9 13 U1 7 U2 30 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 EI 1930-6180 J9 ILAR J JI ILAR J. PY 2014 VL 55 IS 1 BP 59 EP 68 DI 10.1093/ilar/ilu017 PG 10 WC Veterinary Sciences SC Veterinary Sciences GA AK0TD UT WOS:000338127500005 PM 24936030 ER PT J AU Lee, JY Moore, P Kusek, J Barry, M AF Lee, Jeannette Y. Moore, Page Kusek, John Barry, Michael CA CAMUS Study Grp TI Treatment Assignment Guesses by Study Participants in a Double-Blind Dose Escalation Clinical Trial of Saw Palmetto SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID BENIGN PROSTATIC HYPERPLASIA; RANDOMIZED CONTROLLED TRIAL; ASSOCIATION SYMPTOM INDEX; DUTASTERIDE; COMBINATION; FINASTERIDE; THERAPY; PLACEBO AB Objectives: This report assesses participant perception of treatment assignment in a randomized, double-blind, placebo-controlled trial of saw palmetto for the treatment of benign prostatic hyperplasia (BCM). Design: Participants randomized to receive saw palmetto were instructed to take one 320mg gelcap daily for the first 24 weeks, two 320mg gelcaps daily for the second 24 weeks, and three 320mg gelcaps daily for the third 24 weeks. Study participants assigned to placebo were instructed to take the same number of matching placebo gelcaps in each time period. At 24, 48, and 72 weeks postrandomization, the American Urological Association Symptom Index (AUA-SI) was administered and participants were asked to guess their treatment assignment. Settings: The study was conducted at 11 clinical centers in North America. Participants: Study participants were men, 45 years and older, with moderate to low severe BPH symptoms, randomized to saw palmetto (N = 151) or placebo (N = 155). Outcome measures: Treatment arms were compared with respect to the distribution of participant guesses of treatment assignment. Results: For participants assigned to saw palmetto, 22.5%, 24.7%, and 29.8% correctly thought they were taking saw palmetto, and 37.3%, 40.0%, and 44.4% incorrectly thought they were on placebo at 24, 48, and 72 weeks, respectively. For placebo participants, 21.8%, 27.4%, and 25.2% incorrectly thought they were on saw palmetto, and 41.6%, 39.9%, and 42.6% correctly thought they were on placebo at 24, 48, and 72 weeks, respectively. The treatment arms did not vary with respect to the distributions of participants who guessed they were on saw palmetto (p = 0.823) or placebo (p = 0.893). Participants who experienced an improvement in AUA-SI were 2.16 times more likely to think they were on saw palmetto. Conclusions: Blinding of treatment assignment was successful in this study. Improvement in BPH-related symptoms was associated with the perception that participants were taking saw palmetto. C1 [Lee, Jeannette Y.; Moore, Page] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Kusek, John] NIDDK, Bethesda, MD USA. [Barry, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lee, JY (reprint author), Univ Arkansas Med Sci, Dept Biostat, 4301 W Markham, Little Rock, AR 72205 USA. EM jylee@uams.edu FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Complementary and Alternative Medicine [U01 DK63778, U01 DK63788, U01 DK63795, U01 DK63797, U01 DK63825, U01 DK63831, U01 DK63833, U01 DK63835, U01 DK63840, U01 DK63862, U01 DK63866, U01 DK63883]; Office of Dietary Supplements FX This study was funded by grants U01 DK63778, U01 DK63788, U01 DK63795, U01 DK63797, U01 DK63825, U01 DK63831, U01 DK63833, U01 DK63835, U01 DK63840, U01 DK63862, U01 DK63866, and U01 DK63883 from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Complementary and Alternative Medicine, and the Office of Dietary Supplements. Saw palmetto fruit extract and matching placebo were donated by Rottapharm/Madaus, Cologne, Germany. The authors wish to express their appreciation to the full CAMUS study team.6 NR 18 TC 0 Z9 0 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 EI 1557-7708 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD JAN PY 2014 VL 20 IS 1 BP 48 EP 52 DI 10.1089/acm.2012.0284 PG 5 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA AK3SZ UT WOS:000338346300008 PM 23383975 ER PT J AU Bendiabdellah, Y Rahman, KM Uranchimeg, B Nahar, KS Antonow, D Shoemaker, RH Melillo, G Zinzalla, G Thurston, DE AF Bendiabdellah, Y. Rahman, K. M. Uranchimeg, B. Nahar, K. S. Antonow, D. Shoemaker, R. H. Melillo, G. Zinzalla, G. Thurston, D. E. TI Tetracycline analogues with a selective inhibitory effect on HIF-1 alpha SO MEDCHEMCOMM LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1; SMALL-MOLECULE INHIBITORS; CANCER-THERAPY; TARGETING HYPOXIA; TUMOR-GROWTH; HIF-1; PATHWAY; IDENTIFICATION; TRANSCRIPTION; EXPRESSION AB As part of a programme to discover novel transcription factor inhibitors, a 40-membered library of tetracycline analogues was screened to identify potential HIF-1 inhibitors. Two novel analogues (5b and 5c) with significant HIF-1 modulation properties were identified. These molecules possess good cellular penetration properties, and provide significant down-regulation of VEGF in U251 cells. C1 [Bendiabdellah, Y.; Antonow, D.] UCL, Sch Pharm, London WC1N 1AX, England. [Rahman, K. M.; Nahar, K. S.; Thurston, D. E.] Kings Coll London, Inst Pharmaceut Sci, London SE1 1DB, England. [Uranchimeg, B.; Shoemaker, R. H.] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21701 USA. [Melillo, G.] SAIC Frederick, Frederick, MD USA. [Zinzalla, G.] Karolinska Inst, MTC Dept, Ctr Adv Canc Therapies, SE-17177 Stockholm, Sweden. RP Zinzalla, G (reprint author), Karolinska Inst, MTC Dept, Ctr Adv Canc Therapies, Nobelsvag 16, SE-17177 Stockholm, Sweden. EM giovanna.zinzalla@ki.se; david.thurston@kcl.ac.uk OI Zinzalla, Giovanna/0000-0002-1130-4865 FU Cancer Research UK [C180/A9327]; Algerian Government FX Cancer Research UK is acknowledged for providing financial support for these studies (C180/A9327 to D.E.T.), and the Algerian Government is thanked for providing a studentship (to Y.B.). NR 25 TC 0 Z9 0 U1 0 U2 5 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 EI 2040-2511 J9 MEDCHEMCOMM JI MedChemComm PY 2014 VL 5 IS 7 BP 923 EP 926 DI 10.1039/c4md00111g PG 4 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA AK4YW UT WOS:000338431500010 ER PT J AU Jin, S Wu, YZ Deng, SW Zhang, JX Chen, XQ AF Jin, Si Wu, Yongzhong Deng, Shiwei Zhang, Jinxiang Chen, Xiao Qian TI Oxidants and Antioxidants in Metabolic Syndrome and Cancer SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Article ID MODULATION; STRATEGY C1 [Jin, Si] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pharmacol, Wuhan 430030, Peoples R China. [Wu, Yongzhong] NCI, Lab Mol Pharmacol Oxidat Signaling, Ctr Canc Res, Bethesda, MD 20892 USA. [Wu, Yongzhong] NCI, Mol Therapeut Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Deng, Shiwei] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Pharmacol, D-55131 Mainz, Germany. [Zhang, Jinxiang] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Surg, Wuhan 430022, Peoples R China. [Chen, Xiao Qian] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pathophysiol, Wuhan 430030, Peoples R China. RP Jin, S (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pharmacol, Wuhan 430030, Peoples R China. EM jinsi@mails.tjmu.edu.cn NR 8 TC 1 Z9 1 U1 0 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1942-0900 EI 1942-0994 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2014 AR 178962 DI 10.1155/2014/178962 PG 3 WC Cell Biology SC Cell Biology GA AK6PR UT WOS:000338550100001 ER PT J AU Kim, HJ Chuang, DM AF Kim, Hyeon Ju Chuang, De-Maw TI HDAC inhibitors mitigate ischemia-induced oligodendrocyte damage: potential roles of oligodendrogenesis, VEGF, and anti-inflammation SO AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH LA English DT Article DE Anti-inflammation; cerebral ischemia; HDAC inhibitors; myelin basic protein (MBP); oligodendrocytes; vascular endothelial growth factor (VEGF) ID ENDOTHELIAL GROWTH-FACTOR; FOCAL CEREBRAL-ISCHEMIA; WHITE-MATTER INJURY; HISTONE DEACETYLASE INHIBITION; MOOD STABILIZERS LITHIUM; CENTRAL-NERVOUS-SYSTEM; NEURAL STEM-CELLS; SUBVENTRICULAR ZONE; VALPROIC ACID; NEUROTROPHIC FACTOR AB White matter injury is an important component of stroke pathology, but its pathophysiology and potential treatment remain relatively elusive and underexplored. We previously reported that after permanent middle cerebral artery occlusion (pMCAO), sodium butyrate (SB) and trichostatin A (TSA) induced neurogenesis via histone deacetylase (HDAC) inhibition in multiple ischemic brain regions in rats; these effects-which depended on activation of brain-derived neurotrophic factor (BDNF)-TrkB signaling-contributed to behavioral improvement. The present study found that SB or TSA robustly protected against ischemia-induced loss of oligodendrocytes detected by confocal microscopy of myelin basic protein (MBP) immunostaining in the ipsilateral subventricular zone (SVZ), striatum, corpus callosum, and frontal cortex seven days post-pMCAO. Co-localization of 5-bromo-2'-deoxyuridine (BrdU)(+) and MBP+ cells after SB treatment suggested the occurrence of oligodendrogenesis. SB also strongly upregulated vascular endothelial growth factor (VEGF), which plays a major role in neurogenesis, angiogenesis, and functional recovery after stroke. These SB-induced effects were markedly suppressed by blocking the TrkB signaling pathway with K252a. pMCAO-induced activation of microglia (OX42(+)) and macrophages/monocytes (ED1(+))-which has been linked to white matter injury-was robustly suppressed by SB in a K252a-sensitive manner. In addition, SB treatment largely blocked caspase-3(+) and OX42(+) cells in ipsilateral brain regions. Our results suggest that HDAC inhibitor-mediated protection against ischemia-induced oligodendrocyte loss may involve multiple mechanisms including oligodendrogenesis, VEGF upregulation, anti-inflammation, and caspase-3 downregulation. Taken together, the results suggest that post-insult treatment with HDAC inhibitors is a rational strategy to mitigate white matter injury following ischemic stroke. C1 [Kim, Hyeon Ju; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, Bldg 10,Room 3D38,10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov FU Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH) FX This study was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH). We are grateful to Dr. Carolyn Smith of NINDS, NIH for technical assistance with the confocal microscope study. We also thank Ioline Henter, Peter Leeds, and Zhifei Wang of the NIMH, NIH for editorial assistance. NR 65 TC 26 Z9 29 U1 0 U2 6 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1943-8141 J9 AM J TRANSL RES JI Am. J. Transl. Res. PY 2014 VL 6 IS 3 BP 206 EP 223 PG 18 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA AK5BR UT WOS:000338439400003 PM 24936215 ER PT J AU Wang, Y Chen, AM Dietrich, KN Radcliffe, J Caldwell, KL Rogan, WJ AF Wang, Yan Chen, Aimin Dietrich, Kim N. Radcliffe, Jerilynn Caldwell, Kathleen L. Rogan, Walter J. TI Postnatal exposure to methyl mercury and neuropsychological development in 7-year-old urban inner-city children exposed to lead in the United States SO CHILD NEUROPSYCHOLOGY LA English DT Article DE Methyl mercury; Lead; Postnatal exposure; Neuropsychological tests; Cognition; IQ ID PRENATAL METHYLMERCURY EXPOSURE; POLYUNSATURATED FATTY-ACIDS; CHELATION-THERAPY; CHILDBEARING AGE; FISH CONSUMPTION; MATERNAL FISH; US CHILDREN; BLOOD LEAD; PREGNANCY; NEURODEVELOPMENT AB Background: The most common route for general population exposure to methyl mercury (MeHg) is fish consumption. Recommendations to pregnant women about consuming fish contaminated with MeHg are also applied to children, but there are few studies available about the effects of low-level postnatal MeHg exposure in them.Objectives: To investigate the association between postnatal methyl mercury exposure and neuropsychological development in a study of children also exposed to lead, both measured at 7 years.Methods: We measured MeHg concentrations in blood samples from the Treatment of Lead-Exposed Children (TLC) trial in which 780 children with elevated concentrations of lead in blood were followed with neuropsychological tests from ages 12-33 months through 7 years. Here we examine blood MeHg concentration and neuropsychological test scores, both measured at age 7 years. We used a maximum likelihood method to estimate geometric mean MeHg concentration and generalized linear regression models to analyze MeHg and neuropsychological test scores.Results: Geometric mean MeHg concentration was 0.56 (95% confidence interval: 0.52, 0.59) g/L. A1g/L increase in MeHg was associated with a 2.1 (95% confidence interval: 0.4, 3.8) point increase in Full-Scale IQ and 0.2 (95% confidence interval: 0.02, 0.4) point increase in Learning Slopeindex T-score on a test of verbal memory.Conclusions: Our results suggest that the relatively low MeHg exposure in US school-aged children from this population has no detectable adverse effect on neuropsychological development. The positive associations observed between MeHg and neurodevelopment may indirectly reflect consumption of beneficial polyunsaturated fatty acids from seafood. C1 [Wang, Yan; Rogan, Walter J.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Chen, Aimin; Dietrich, Kim N.] Univ Cincinnati, Coll Med, Div Epidemiol & Biostat, Dept Environm Hlth, Cincinnati, OH 45267 USA. [Radcliffe, Jerilynn] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Caldwell, Kathleen L.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Inorgan & Radiat Analyt Toxicol Branch, Atlanta, GA USA. RP Dietrich, KN (reprint author), Univ Cincinnati, Coll Med, Div Epidemiol & Biostat, Dept Environm Hlth, 3223 Eden Ave,Room G-31,ML 056, Cincinnati, OH 45267 USA. EM kim.dietrich@uc.edu RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 FU US National Institute of Environmental Health Sciences/National Institutes of Health FX This study was supported by the Intramural Research Program of the US National Institute of Environmental Health Sciences/National Institutes of Health. We thank Dr. Robert Jones, National Center for Environmental Health of the CDC, for help with the measurement of Hg and the editorial assistance of NIH Fellows Editorial Board. NR 37 TC 2 Z9 2 U1 0 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0929-7049 EI 1744-4136 J9 CHILD NEUROPSYCHOL JI Child Neuropsychol. PY 2014 VL 20 IS 5 BP 527 EP 538 DI 10.1080/09297049.2013.824955 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA AJ8QE UT WOS:000337970600003 PM 23971942 ER PT J AU Adhya, S Merril, CR Biswas, B AF Adhya, Sankar Merril, Carl R. Biswas, Biswajit TI Therapeutic and Prophylactic Applications of Bacteriophage Components in Modern Medicine SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID ESCHERICHIA-COLI; PHAGE DISPLAY; FUNCTIONAL DISPLAY; VACCINE ADJUVANTS; GENE-EXPRESSION; CAPSID PROTEIN; LYTIC ENZYME; HUMAN CELLS; LAMBDA; IMMUNIZATION AB As the interactions of phage with mammalian innate and adaptive immune systems are better delineated and with our ability to recognize and eliminate toxins and other potentially harmful phage gene products, the potential of phage therapies is now being realized. Early efforts to use phage therapeutically were hampered by inadequate phage purification and limited knowledge of phage-bacterial and phage-human relations. However, although use of phage as an antibacterial therapy in countries that require controlled clinical studies has been hampered by the high costs of patient trials, their use as vaccines and the use of phage components such as lysolytic enzymes or lysozymes has progressed to the point of commercial applications. Recent studies concerning the intimate associations between mammalian hosts and bacterial and phage microbiomes should hasten this progress. C1 [Adhya, Sankar] NCI, NIH, Bethesda, MD 20892 USA. [Merril, Carl R.] NIMH, NIH, Bethesda, MD 20892 USA. [Biswas, Biswajit] Naval Med Res Ctr, Dept Genom Biol Def Res Directorate, Ft Detrick, MD 21702 USA. RP Adhya, S (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov NR 81 TC 8 Z9 8 U1 2 U2 12 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 JAN PY 2014 VL 4 IS 1 AR a012518 DI 10.1101/cshperspect.a012518 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AJ9HD UT WOS:000338017900001 PM 24384811 ER PT J AU Lee, YJ Zhang, XZ Vazquez, E Shivasabesan, G Young, HA Murphy, A Wang, HH Suffredini, AF Siebenlist, U Kottilil, S AF Lee, Yu-Jin Zhang, Xiaozhen Vazquez, Estefania Shivasabesan, Gayathri Young, Howard A. Murphy, Alison Wang, Honghui Suffredini, Anthony F. Siebenlist, Ulrich Kottilil, Shyam TI Impaired HCV Clearance in HIV/HCV Coinfected Subjects Treated with PegIFN and RBV Due to Interference of IFN Signaling by IFN alpha R2a SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID CHRONIC HEPATITIS-C; ALPHA-2A PLUS RIBAVIRIN; VIRUS-INFECTION; RECEPTOR-ALPHA; IN-VIVO; EXPRESSION; IL-15; SERUM AB Enhanced endogenous interferon (IFN) stimulated gene (ISG) signature has been associated with nonresponsiveness to hepatitis C treatment using pegylated-IFN alpha (pegIFN alpha) and ribavirin (RBV) in human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfected patients. Using a proteomic approach, we identified high levels of IFN alpha receptor 2a (IFN alpha R2a) in the serum of null responders to pegIFN alpha/RBV. IFN alpha R2a inhibited antiviral activity of all formulations of IFN alpha in JFH/Huh7.5 cells. Furthermore, serum from null responders, but not from those who achieved sustained virologic response, suppressed IFN-signaling and ISG expression in IFN alpha-stimulated PBMCs of healthy donors in an IFN alpha R2a specific fashion. An IFN alpha R2a transgenic mice model (C57BL/6) was generated that had significantly higher levels of IFN alpha R2a in the serum than the controls (P = 0.001). Total ISG expression in the lymph nodes was significantly higher compared to wild-type mice (P value = 0.0016). In addition, IFITM1 and SP110 had significantly increased expression in the liver, IFITM1 and ISG15 in the lymph node, and ISG15 and PLSCR1 in the spleen (P value < 0.05). The underlying mechanism of resistance to hepatitis C treatment may involve transsignaling of the JAK/STAT pathway by the sIFN alpha R2a-IFN alpha/beta complex and result in the enhanced ISG signature observed in null responders. In this regard, the transgenic mice model simulated nonresponders to IFN alpha therapy and provides valuable insights into the role of sIFN alpha R2a-IFN alpha interactions in vivo. C1 [Lee, Yu-Jin; Zhang, Xiaozhen; Shivasabesan, Gayathri; Murphy, Alison; Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20814 USA. [Vazquez, Estefania; Siebenlist, Ulrich] NIAID, Immune Activat Sect, NIH, Bethesda, MD 20814 USA. [Young, Howard A.] NCI, Expt Immunol Lab, Bethesda, MD 20892 USA. [Wang, Honghui; Suffredini, Anthony F.] NIH, Clin Res Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Kottilil, S (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg10,Rm 11N204,10 Ctr Dr, Bethesda, MD 20814 USA. EM skottilil@niaid.nih.gov FU NIH (National Institute of Allergy and Infectious Diseases); NIH (National Cancer Institute); NIH (Clinical Research Center) FX This research was supported in whole by the Intramural Research Program of the NIH (National Institute of Allergy and Infectious Diseases, National Cancer Institute and the Clinical Research Center). We acknowledge Apath LLC for providing us with J6/JFH-1 HCV clone and Huh7.5 cells. NR 24 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 EI 1557-7465 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD JAN PY 2014 VL 34 IS 1 BP 28 EP 34 DI 10.1089/jir.2013.0032 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA AJ8NX UT WOS:000337963600005 PM 24171456 ER PT S AU Cherry, KM Wang, SJ Turkbey, EB Summers, RM AF Cherry, Kevin M. Wang, Shijun Turkbey, Evrim B. Summers, Ronald M. BE Aylward, S Hadjiiski, LM TI Abdominal Lymphadenopathy Detection using Random Forest SO MEDICAL IMAGING 2014: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 18-20, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN, Inc, Ventana Med Syst Inc, Intrace Med DE lymphadenopathy; lymph nodes; computed tomography; computer-aided detection; machine learning; random forest; support vector machines ID LYMPH-NODES; RECOGNITION; EXTRACTION AB We propose a new method for detecting abdominal lymphadenopathy by utilizing a random forest statistical classifier to create voxel-level lymph node predictions, i.e. initial detection of enlarged lymph nodes. The framework permits the combination of multiple statistical lymph node descriptors and appropriate feature selection in order to improve lesion detection beyond traditional enhancement filters. We show that Hessian blobness measurements alone are inadequate for detecting lymph nodes in the abdominal cavity. Of the features tested here, intensity proved to be the most important predictor for lymph node classification. For initial detection, candidate lesions were extracted from the 3D prediction map generated by random forest. Statistical features describing intensity distribution, shape, and texture were calculated from each enlarged lymph node candidate. In the last step, a support vector machine (SVM) was trained and tested based on the calculated features from candidates and labels determined by two experienced radiologists. The computer-aided detection (CAD) system was tested on a dataset containing 30 patients with 119 enlarged lymph nodes. Our method achieved an AUC of 0.762+/-0.022 and a sensitivity of 79.8% with 15 false positives suggesting it can aid radiologists in finding enlarged lymph nodes. C1 [Cherry, Kevin M.; Wang, Shijun; Turkbey, Evrim B.; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10 Room 1C224 MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov NR 13 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9828-1 J9 PROC SPIE PY 2014 VL 9035 AR 90351G DI 10.1117/12.2043837 PG 6 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7XB UT WOS:000337842400048 ER PT S AU Liu, JM Zhao, J Hoffman, J Yao, JH Zhang, WD Turkbey, EB Wang, SJ Kim, C Summers, RM AF Liu, Jiamin Zhao, Jocelyn Hoffman, Joanne Yao, Jianhua Zhang, Weidong Turkbey, Evrim B. Wang, Shijun Kim, Christine Summers, Ronald M. BE Aylward, S Hadjiiski, LM TI Mediastinal Lymph Node Detection on Thoracic CT Scans Using Spatial Prior from Multi-atlas Label Fusion SO MEDICAL IMAGING 2014: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 18-20, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN, Inc, Ventana Med Syst Inc, Intrace Med DE mediastinal lymph node detection; multi-atlas label fusion; spatial prior ID IMAGES AB Lymph nodes play an important role in clinical practice but detection is challenging due to low contrast surrounding structures and variable size and shape. We propose a fully automatic method for mediastinal lymph node detection on thoracic CT scans. First, lungs are automatically segmented to locate the mediastinum region. Shape features by Hessian analysis, local scale, and circular transformation are computed at each voxel. Spatial prior distribution is determined based on the identification of multiple anatomical structures ( esophagus, aortic arch, heart, etc.) by using multi-atlas label fusion. Shape features and spatial prior are then integrated for lymph node detection. The detected candidates are segmented by curve evolution. Characteristic features are calculated on the segmented lymph nodes and support vector machine is utilized for classification and false positive reduction. We applied our method to 20 patients with 62 enlarged mediastinal lymph nodes. The system achieved a significant improvement with 80% sensitivity at 8 false positives per patient with spatial prior compared to 45% sensitivity at 8 false positives per patient without a spatial prior. C1 [Liu, Jiamin; Zhao, Jocelyn; Hoffman, Joanne; Yao, Jianhua; Zhang, Weidong; Turkbey, Evrim B.; Wang, Shijun; Kim, Christine; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Liu, JM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9828-1 J9 PROC SPIE PY 2014 VL 9035 AR 90350M DI 10.1117/12.2043737 PG 7 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7XB UT WOS:000337842400020 ER PT S AU Lu, L Yao, JH Turkbey, E Summers, RM AF Lu, Le Yao, Jianhua Turkbey, Evrim Summers, Ronald M. BE Aylward, S Hadjiiski, LM TI Multilevel Image Recognition using Discriminative Patches and Kernel Covariance Descriptor SO MEDICAL IMAGING 2014: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 18-20, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN, Inc, Ventana Med Syst Inc, Intrace Med DE Computer-Aided Detection; Multilevel Image Recognition; Discriminative Image Patch Mining; Covariance Descriptor; Kernel Distance Metric; Support Vector Machine ID SEGMENTATION; CT; FEATURES; HEART; MODEL AB Computer-aided diagnosis of medical images has emerged as an important tool to objectively improve the performance, accuracy and consistency for clinical workflow. To computerize the medical image diagnostic recognition problem, there are three fundamental problems: where to look (i.e., where is the region of interest from the whole image/volume), image feature description/encoding, and similarity metrics for classification or matching. In this paper, we exploit the motivation, implementation and performance evaluation of task-driven iterative, discriminative image patch mining; covariance matrix based descriptor via intensity, gradient and spatial layout; and log-Euclidean distance kernel for support vector machine, to address these three aspects respectively. To cope with often visually ambiguous image patterns for the region of interest in medical diagnosis, discovery of multilabel selective discriminative patches is desired. Covariance of several image statistics summarizes their second order interactions within an image patch and is proved as an effective image descriptor, with low dimensionality compared with joint statistics and fast computation regardless of the patch size. We extensively evaluate two extended Gaussian kernels using affine-invariant Riemannian metric or log-Euclidean metric with support vector machines (SVM), on two medical image classification problems of degenerative disc disease (DDD) detection on cortical shell unwrapped CT maps and colitis detection on CT key images. The proposed approach is validated with promising quantitative results on these challenging tasks. Our experimental findings and discussion also unveil some interesting insights on the covariance feature composition with or without spatial layout for classification and retrieval, and different kernel constructions for SVM. This will also shed some light on future work using covariance feature and kernel classification for medical image analysis. C1 [Lu, Le] NIH, Clin Image Proc Serv, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NIH, Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Lu, L (reprint author), NIH, Clin Image Proc Serv, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. FU Intramural Research Program of the NIH Clinical Center FX This research was supported by the Intramural Research Program of the NIH Clinical Center. NR 21 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9828-1 J9 PROC SPIE PY 2014 VL 9035 AR UNSP 903528 DI 10.1117/12.2043692 PG 8 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7XB UT WOS:000337842400075 ER PT S AU Munoz, HE Yao, JH Burns, JE Pham, Y Stieger, J Summers, RM AF Munoz, Hector E. Yao, Jianhua Burns, Joseph E. Pham, Yasuyuki Stieger, James Summers, Ronald M. BE Aylward, S Hadjiiski, LM TI Vertebral Degenerative Disc Disease Severity Evaluation Using Random Forest Classification SO MEDICAL IMAGING 2014: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 18-20, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN, Inc, Ventana Med Syst Inc, Intrace Med DE Degenerative disc disease; computer-aided detection ID SPINE AB Degenerative disc disease (DDD) develops in the spine as vertebral discs degenerate and osseous excrescences or outgrowths naturally form to restabilize unstable segments of the spine. These osseous excrescences, or osteophytes, may progress or stabilize in size as the spine reaches a new equilibrium point. We have previously created a CAD system that detects DDD. This paper presents a new system to determine the severity of DDD of individual vertebral levels. This will be useful to monitor the progress of developing DDD, as rapid growth may indicate that there is a greater stabilization problem that should be addressed. The existing DDD CAD system extracts the spine from CT images and segments the cortical shell of individual levels with a dual-surface model. The cortical shell is unwrapped, and is analyzed to detect the hyperdense regions of DDD. Three radiologists scored the severity of DDD of each disc space of 46 CT scans. Radiologists' scores and features generated from CAD detections were used to train a random forest classifier. The classifier then assessed the severity of DDD at each vertebral disc level. The agreement between the computer severity score and the average radiologist's score had a quadratic weighted Cohen's kappa of 0.64. C1 [Munoz, Hector E.; Yao, Jianhua; Stieger, James; Summers, Ronald M.] NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA. [Burns, Joseph E.; Pham, Yasuyuki] Univ Calif Irvine, Irvine Sch Med, Dept Radiol Sci, Irvine, CA USA. RP Munoz, HE (reprint author), NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA. FU National Institutes of Health, Clinical Center FX This work was supported by the Intramural Research Program at National Institutes of Health, Clinical Center. NR 7 TC 1 Z9 1 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9828-1 J9 PROC SPIE PY 2014 VL 9035 AR UNSP 90353A DI 10.1117/12.2042793 PG 8 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7XB UT WOS:000337842400112 ER PT S AU Zhang, WD Liu, JM Yao, JH Summers, RM AF Zhang, Weidong Liu, Jiamin Yao, Jianhua Summers, Ronald M. BE Aylward, S Hadjiiski, LM TI Reducing False Positives of Small Bowel Segmentation on CT Scans by Localizing Colon Regions SO MEDICAL IMAGING 2014: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 18-20, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN, Inc, Ventana Med Syst Inc, Intrace Med DE Small bowel segmentation; probability map; Haralick features; CT ID ARTERIES AB Automated small bowel segmentation is essential for computer-aided diagnosis (CAD) of small bowel pathology, such as tumor detection and pre-operative planning. We previously proposed a method to segment the small bowel using the mesenteric vasculature as a roadmap. The method performed well on small bowel segmentation but produced many false positives, most of which were located on the colon. To improve the accuracy of small bowel segmentation, we propose a semi-automated method with minimum interaction to distinguish the colon from the small bowel. The method utilizes anatomic knowledge about the mesenteric vasculature and a statistical method of colon detection. First, anatomic labeling of the mesenteric arteries is used to identify the arteries supplying the colon. Second, a statistical detector is created by combining two colon probability maps. One probability map is of the colon location and is generated from colon centerlines generated from CT colonography (CTC) data. Another probability map is of 3D colon texture using Haralick features and support vector machine (SVM) classifiers. The two probability maps are combined to localize colon regions, i.e., voxels having high probabilities on both maps were labeled as colon. Third, colon regions identified by anatomical labeling and the statistical detector are removed from the original results of small bowel segmentation. The method was evaluated on 11 abdominal CT scans of patients suspected of having carcinoid tumors. The reference standard consisted of manually-labeled small bowel segmentation. The method reduced the voxel-based false positive rate of small bowel segmentation from 19.7%+/-3.9% to 5.9%+/-2.3%, with two-tailed P-value <0.0001. C1 [Zhang, Weidong; Liu, Jiamin; Yao, Jianhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Zhang, WD (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM rms@nih.gov NR 17 TC 1 Z9 1 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9828-1 J9 PROC SPIE PY 2014 VL 9035 AR 90350Z DI 10.1117/12.2043344 PG 7 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7XB UT WOS:000337842400031 ER PT J AU Dodson, GT Boker, SM Evans, MK Zonderman, AB AF Dodson, Geneva T. Boker, Steven M. Evans, Michele K. Zonderman, Alan B. TI An Investigation of Construct Validity Using Higher Order Invariance SO MULTIVARIATE BEHAVIORAL RESEARCH LA English DT Meeting Abstract C1 [Dodson, Geneva T.; Boker, Steven M.] Univ Virginia, Charlottesville, VA 22903 USA. [Evans, Michele K.; Zonderman, Alan B.] NIA, Bethesda, MD 20892 USA. EM genevad@email.virginia.edu NR 2 TC 0 Z9 0 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0027-3171 EI 1532-7906 J9 MULTIVAR BEHAV RES JI Multivariate Behav. Res. PY 2014 VL 49 IS 3 BP 284 EP 284 DI 10.1080/00273171.2014.912888 PG 1 WC Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods; Psychology, Experimental; Statistics & Probability SC Mathematics; Mathematical Methods In Social Sciences; Psychology GA AJ8HB UT WOS:000337942800009 PM 26735194 ER PT J AU Nussinov, R AF Nussinov, Ruth TI The Significance of the 2013 Nobel Prize in Chemistry and the Challenges Ahead SO PLOS COMPUTATIONAL BIOLOGY LA English DT Editorial Material C1 [Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. EM NussinoR@helix.nih.gov NR 0 TC 3 Z9 4 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JAN PY 2014 VL 10 IS 1 AR e1003423 DI 10.1371/journal.pcbi.1003423 PG 2 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA AJ8JE UT WOS:000337948500023 PM 24391489 ER PT J AU Anuradha, R George, PJ Hanna, LE Chandrasekaran, V Kumaran, PP Nutman, TB Babu, S AF Anuradha, Rajamanickam George, Parakkal Jovvian Hanna, Luke E. Chandrasekaran, Vedachalam Kumaran, P. Paul Nutman, Thomas B. Babu, Subash TI Parasite-Antigen Driven Expansion of IL-5(-) and IL-5(+) Th2 Human Subpopulations in Lymphatic Filariasis and Their Differential Dependence on IL-10 and TGF beta SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID HOST-DEFENSE; IMMUNITY; CELLS; INFECTIONS; INTERFERON; PATHWAYS; MICE AB Background: Two different Th2 subsets have been defined recently on the basis of IL-5 expression - an IL-5(+)Th2 subset and an IL-5(-)Th2 subset in the setting of allergy. However, the role of these newly described CD4(+) T cells subpopulations has not been explored in other contexts. Methods: To study the role of the Th2 subpopulation in a chronic, tissue invasive parasitic infection (lymphatic filariasis), we examined the frequency of IL-5(+)IL-4(+)IL-13(+) CD4(+) T cells and IL-5(-)IL-4 IL-13(+) CD4(+) T cells in asymptomatic, infected individuals (INF) and compared them to frequencies (F-o) in filarial-uninfected (UN) individuals and to those with filarial lymphedema (CP). Results: INF individuals exhibited a significant increase in the spontaneously expressed and antigen-induced F-o of both Th2 subpopulations compared to the UN and CP. Interestingly, there was a positive correlation between the F-o of IL-5(+)Th2 cells and the absolute eosinophil and neutrophil counts; in addition there was a positive correlation between the frequency of the CD4(+)IL-5(-)Th2 subpopulation and the levels of parasite antigen - specific IgE and IgG4 in INF individuals. Moreover, blockade of IL-10 and/or TGF beta demonstrated that each of these 2 regulatory cytokines exert opposite effects on the different Th2 subsets. Finally, in those INF individuals cured of infection by anti-filarial therapy, there was a significantly decreased F-o of both Th2 subsets. Conclusions: Our findings suggest that both IL-5(+) and IL-5(-)Th2 cells play an important role in the regulation of immune responses in filarial infection and that these two Th2 subpopulations may be regulated by different cytokine-receptor mediated processes. C1 [Anuradha, Rajamanickam; George, Parakkal Jovvian; Babu, Subash] Natl Inst Hlth, Int Ctr Excellence Res, Chennai, Tamil Nadu, India. [Hanna, Luke E.; Nutman, Thomas B.; Babu, Subash] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Chandrasekaran, Vedachalam; Kumaran, P. Paul] Natl Inst Res TB, Chennai, Tamil Nadu, India. RP Anuradha, R (reprint author), Natl Inst Hlth, Int Ctr Excellence Res, Chennai, Tamil Nadu, India. EM sbabu@mail.nih.gov FU Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish or preparation of manuscript. NR 26 TC 4 Z9 4 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2014 VL 8 IS 1 AR e2658 DI 10.1371/journal.pntd.0002658 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AJ8SI UT WOS:000337977300048 PM 24498448 ER PT J AU Bisoffi, Z Buonfrate, D Sequi, M Mejia, R Cimino, RO Krolewiecki, AJ Albonico, M Gobbo, M Bonafini, S Angheben, A Requena-Mendez, A Munoz, J Nutman, TB AF Bisoffi, Zeno Buonfrate, Dora Sequi, Marco Mejia, Rojelio Cimino, Ruben O. Krolewiecki, Alejandro J. Albonico, Marco Gobbo, Maria Bonafini, Stefania Angheben, Andrea Requena-Mendez, Ana Munoz, Jose Nutman, Thomas B. TI Diagnostic Accuracy of Five Serologic Tests for Strongyloides stercoralis Infection SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID FOLLOW-UP; ASSAY; IMMIGRANTS AB Background: The diagnosis of Strongyloides stercoralis (S. stercoralis) infection is hampered by the suboptimal sensitivity of fecal-based tests. Serological methods are believed to be more sensitive, although assessing their accuracy is difficult because of the lack of sensitivity of a fecal-based reference ("gold") standard. Methods: The sensitivity and specificity of 5 serologic tests for S. stercoralis (in-house IFAT, NIE-ELISA and NIE-LIPS and the commercially available Bordier-ELISA and IVD-ELISA) were assessed on 399 cryopreserved serum samples. Accuracy was measured using fecal results as the primary reference standard, but also using a composite reference standard (based on a combination of tests). Results: According to the latter standard, the most sensitive test was IFAT, with 94.6% sensitivity (91.2-96.9), followed by IVD-ELISA (92.3%, 87.7-96.9). The most specific test was NIE-LIPS, with specificity 99.6% (98.9-100), followed by IVD-ELISA (97.4%, 95.5-99.3). NIE-LIPS did not cross-react with any of the specimens from subjects with other parasitic infections. NIE-LIPS and the two commercial ELISAs approach 100% specificity at a cut off level that maintains >= 70% sensitivity. Conclusions: NIE-LIPS is the most accurate serologic test for the diagnosis of S. stercoralis infection. IFAT and each of the ELISA tests are sufficiently accurate, above a given cut off, for diagnosis, prevalence studies and inclusion in clinical trials. C1 [Bisoffi, Zeno; Buonfrate, Dora; Albonico, Marco; Gobbo, Maria; Bonafini, Stefania; Angheben, Andrea] Sacro Cuore Hosp, CTD, Verona, Italy. [Sequi, Marco] IRCCS Mario Negri Inst Pharmacol Res, Dept Publ Hlth, Milan, Italy. [Mejia, Rojelio; Nutman, Thomas B.] NIAID, NIH, Bethesda, MD 20892 USA. [Cimino, Ruben O.; Krolewiecki, Alejandro J.] Univ Nacl Salta, CONICET, Inst Invest Enfermedades Trop, Oran, Argentina. [Requena-Mendez, Ana; Munoz, Jose] Univ Barcelona, Hosp Clinic, Barcelona Ctr Int Hlth Res, CRESIB, Barcelona, Spain. RP Bisoffi, Z (reprint author), Sacro Cuore Hosp, CTD, Verona, Italy. EM zeno.bisoffi@sacrocuore.it OI Munoz Gutierrez, Jose/0000-0002-0945-1735; ALBONICO, Marco/0000-0002-7805-2391 FU EC within the 7th Framework Programme under the COHEMI project [FP7-GA-261495] FX This work has been partly supported by the EC within the 7th Framework Programme under the COHEMI project - grant agreement no. FP7-GA-261495. We thank Bordier Affinity Products SA for donating the Bordier ELISA kits. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 21 TC 40 Z9 41 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2014 VL 8 IS 1 AR e2640 DI 10.1371/journal.pntd.0002640 PG 8 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AJ8SI UT WOS:000337977300036 PM 24427320 ER PT J AU Pitzer, VE Bowles, CC Baker, S Kang, G Balaji, V Farrar, JJ Grenfell, BT AF Pitzer, Virginia E. Bowles, Cayley C. Baker, Stephen Kang, Gagandeep Balaji, Veeraraghavan Farrar, Jeremy J. Grenfell, Bryan T. TI Predicting the Impact of Vaccination on the Transmission Dynamics of Typhoid in South Asia: A Mathematical Modeling Study SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID VI CAPSULAR POLYSACCHARIDE; SALMONELLA-TYPHI; GALLBLADDER CARRIAGE; IMMUNOLOGIC CONTROL; CONJUGATE VACCINE; GLOBAL BURDEN; FEVER; CHILDREN; TRIAL; STATE AB Background: Modeling of the transmission dynamics of typhoid allows for an evaluation of the potential direct and indirect effects of vaccination; however, relevant typhoid models rooted in data have rarely been deployed. Methodology/Principal Findings: We developed a parsimonious age-structured model describing the natural history and immunity to typhoid infection. The model was fit to data on culture-confirmed cases of typhoid fever presenting to Christian Medical College hospital in Vellore, India from 2000-2012. The model was then used to evaluate the potential impact of school-based vaccination strategies using live oral, Vi-polysaccharide, and Vi-conjugate vaccines. The model was able to reproduce the incidence and age distribution of typhoid cases in Vellore. The basic reproductive number (R-0) of typhoid was estimated to be 2.8 in this setting. Vaccination was predicted to confer substantial indirect protection leading to a decrease in the incidence of typhoid in the short term, but (intuitively) typhoid incidence was predicted to rebound 515 years following a one-time campaign. Conclusions/Significance: We found that model predictions for the overall and indirect effects of vaccination depend strongly on the role of chronic carriers in transmission. Carrier transmissibility was tentatively estimated to be low, consistent with recent studies, but was identified as a pivotal area for future research. It is unlikely that typhoid can be eliminated from endemic settings through vaccination alone. C1 [Pitzer, Virginia E.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06520 USA. [Pitzer, Virginia E.; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Bowles, Cayley C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bowles, Cayley C.; Farrar, Jeremy J.; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Baker, Stephen; Farrar, Jeremy J.] Univ Oxford, Clin Res Unit, Wellcome Trust Major Overseas Programme, Hosp Trop Dis, Ho Chi Minh City, Vietnam. [Baker, Stephen; Farrar, Jeremy J.] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England. [Baker, Stephen] London Sch Hyg & Trop Med, London WC1, England. [Kang, Gagandeep; Balaji, Veeraraghavan] Christian Med Coll & Hosp, Dept Gastrointestinal Sci, Vellore, Tamil Nadu, India. RP Pitzer, VE (reprint author), Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06520 USA. EM virginia.pitzer@yale.edu OI Farrar, Jeremy/0000-0002-2700-623X; Pitzer, Virginia/0000-0003-1015-2289; Kang, Gagandeep/0000-0002-3656-564X FU Bill & Melinda Gates Foundation; RAPIDD program of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; Wellcome Trust; Coalition against Typhoid FX This work was supported by the Bill & Melinda Gates Foundation (http://www.gatesfoundation.org/), the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health (VEP and BTG), and the Wellcome Trust (http://www.wellcome.ac.uk/) (SB and JJF). Travel funding for VEP, BTG, and JJF was also provided by the Coalition against Typhoid (http://www.coalitionagainsttyphoid.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 14 Z9 14 U1 3 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2014 VL 8 IS 1 AR e2642 DI 10.1371/journal.pntd.0002642 PG 12 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AJ8SI UT WOS:000337977300038 PM 24416466 ER PT J AU Ribeiro, JMC Genta, FA Sorgine, MHF Logullo, R Mesquita, RD Paiva-Silva, GO Majerowicz, D Medeiros, M Koerich, L Terra, WR Ferreira, C Pimentel, AC Bisch, PM Leite, DC Diniz, MMP Junior, JLDGV Da Silva, ML Araujo, RN Gandara, ACP Brosson, S Salmon, D Bousbata, S Gonzalez-Caballero, N Silber, AM Alves-Bezerra, M Gondim, KC Silva-Neto, MAC Atella, GC Araujo, H Dias, FA Polycarpo, C Vionette-Amaral, RJ Fampa, P Melo, ACA Tanaka, AS Balczun, C Oliveira, JHM Goncalves, RLS Lazoski, C Rivera-Pomar, R Diambra, L Schaub, GA Garcia, ES Azambuja, P Braz, GRC Oliveira, PL AF Ribeiro, Jose M. C. Genta, Fernando A. Sorgine, Marcos H. F. Logullo, Raquel Mesquita, Rafael D. Paiva-Silva, Gabriela O. Majerowicz, David Medeiros, Marcelo Koerich, Leonardo Terra, Walter R. Ferreira, Clelia Pimentel, Andre C. Bisch, Paulo M. Leite, Daniel C. Diniz, Michelle M. P. Junior, Joao Lidio da S. G. V. Da Silva, Manuela L. Araujo, Ricardo N. Gandara, Ana Caroline P. Brosson, Sebastien Salmon, Didier Bousbata, Sabrina Gonzalez-Caballero, Natalia Silber, Ariel Mariano Alves-Bezerra, Michele Gondim, Katia C. Silva-Neto, Mario Alberto C. Atella, Georgia C. Araujo, Helena Dias, Felipe A. Polycarpo, Carla Vionette-Amaral, Raquel J. Fampa, Patricia Melo, Ana Claudia A. Tanaka, Aparecida S. Balczun, Carsten Oliveira, Jose Henrique M. Goncalves, Renata L. S. Lazoski, Cristiano Rivera-Pomar, Rolando Diambra, Luis Schaub, Guenter A. Garcia, Eloi S. Azambuja, Patricia Braz, Gloria R. C. Oliveira, Pedro L. TI An Insight into the Transcriptome of the Digestive Tract of the Bloodsucking Bug, Rhodnius prolixus SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID TRIATOMA-BRASILIENSIS HEMIPTERA; TRANSFER-RNA MODIFICATIONS; ACTIVATED PROTEIN-KINASE; INDUCED OXIDATIVE STRESS; HEME-BINDING PROTEIN; FULL-LENGTH CDNA; AEDES-AEGYPTI; DROSOPHILA-MELANOGASTER; SEQUENCE CHARACTERIZATION; TRYPANOSOMA-CRUZI AB The bloodsucking hemipteran Rhodnius prolixus is a vector of Chagas' disease, which affects 7-8 million people today in Latin America. In contrast to other hematophagous insects, the triatomine gut is compartmentalized into three segments that perform different functions during blood digestion. Here we report analysis of transcriptomes for each of the segments using pyrosequencing technology. Comparison of transcript frequency in digestive libraries with a whole-body library was used to evaluate expression levels. All classes of digestive enzymes were highly expressed, with a predominance of cysteine and aspartic proteinases, the latter showing a significant expansion through gene duplication. Although no protein digestion is known to occur in the anterior midgut (AM), protease transcripts were found, suggesting secretion as proenzymes, being possibly activated in the posterior midgut (PM). As expected, genes related to cytoskeleton, protein synthesis apparatus, protein traffic, and secretion were abundantly transcribed. Despite the absence of a chitinous peritrophic membrane in hemipterans - which have instead a lipidic perimicrovillar membrane lining over midgut epithelia several gut-specific peritrophin transcripts were found, suggesting that these proteins perform functions other than being a structural component of the peritrophic membrane. Among immunity-related transcripts, while lysozymes and lectins were the most highly expressed, several genes belonging to the Toll pathway - found at low levels in the gut of most insects were identified, contrasting with a low abundance of transcripts from IMD and STAT pathways. Analysis of transcripts related to lipid metabolism indicates that lipids play multiple roles, being a major energy source, a substrate for perimicrovillar membrane formation, and a source for hydrocarbons possibly to produce the wax layer of the hindgut. Transcripts related to amino acid metabolism showed an unanticipated priority for degradation of tyrosine, phenylalanine, and tryptophan. Analysis of transcripts related to signaling pathways suggested a role for MAP kinases, GTPases, and LKBP1/AMP kinases related to control of cell shape and polarity, possibly in connection with regulation of cell survival, response of pathogens and nutrients. Together, our findings present a new view of the triatomine digestive apparatus and will help us understand trypanosome interaction and allow insights into hemipteran metabolic adaptations to a blood-based diet. C1 [Ribeiro, Jose M. C.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20892 USA. [Genta, Fernando A.; Sorgine, Marcos H. F.; Mesquita, Rafael D.; Paiva-Silva, Gabriela O.; Koerich, Leonardo; Terra, Walter R.; Ferreira, Clelia; Araujo, Ricardo N.; Gondim, Katia C.; Silva-Neto, Mario Alberto C.; Atella, Georgia C.; Araujo, Helena; Polycarpo, Carla; Vionette-Amaral, Raquel J.; Melo, Ana Claudia A.; Tanaka, Aparecida S.; Lazoski, Cristiano; Garcia, Eloi S.; Azambuja, Patricia; Braz, Gloria R. C.; Oliveira, Pedro L.] Univ Fed Rio de Janeiro, Inst Nacl Ciencia & Tecnol Entomol Mol, Rio De Janeiro, Brazil. [Genta, Fernando A.] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Rio De Janeiro, Brazil. [Sorgine, Marcos H. F.; Paiva-Silva, Gabriela O.; Majerowicz, David; Gandara, Ana Caroline P.; Salmon, Didier; Alves-Bezerra, Michele; Gondim, Katia C.; Silva-Neto, Mario Alberto C.; Atella, Georgia C.; Dias, Felipe A.; Polycarpo, Carla; Vionette-Amaral, Raquel J.; Oliveira, Jose Henrique M.; Goncalves, Renata L. S.; Oliveira, Pedro L.] Univ Fed Rio de Janeiro, Inst Bioquim Med, Programa Biotecnol & Biol Mol, Rio De Janeiro, Brazil. [Logullo, Raquel; Mesquita, Rafael D.; Melo, Ana Claudia A.; Braz, Gloria R. C.] Univ Fed Rio de Janeiro, Inst Chem, Dept Biochem, Rio De Janeiro, Brazil. [Medeiros, Marcelo; Da Silva, Manuela L.] Programa Biotecnol, Diretoria Metrol Aplicada Ciencias Vida, Inst Nacl Metrol Qualidade & Tecnol, BR-25250020 Rio De Janeiro, Brazil. [Koerich, Leonardo] Univ Fed Rio de Janeiro, Inst Biol, Dept Genet, BR-21944970 Rio De Janeiro, Brazil. [Terra, Walter R.; Ferreira, Clelia; Pimentel, Andre C.] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-01498 Sao Paulo, Brazil. [Bisch, Paulo M.; Leite, Daniel C.; Diniz, Michelle M. P.; Junior, Joao Lidio da S. G. V.; Da Silva, Manuela L.] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21941 Rio De Janeiro, Brazil. [Junior, Joao Lidio da S. G. V.] Evandro Chagas Inst, Ctr Technol Innovat, Ananindeua, Para, Brazil. [Araujo, Ricardo N.] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Parasitol, Belo Horizonte, MG, Brazil. [Brosson, Sebastien; Bousbata, Sabrina] Univ Libre Bruxelles, IBMM, Gosselies, Belgium. [Silber, Ariel Mariano] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508 Sao Paulo, Brazil. [Araujo, Helena] Univ Fed Rio de Janeiro, Inst Biomed Sci, Rio De Janeiro, Brazil. [Fampa, Patricia] Univ Fed Rural Rio de Janeiro, DBA, Inst Biol, Rio de Janeiro, Brazil. [Tanaka, Aparecida S.] Univ Fed Sao Paulo, Escola Paulista Med, Dept Bioquim, Sao Paulo, Brazil. [Balczun, Carsten; Schaub, Guenter A.] Ruhr Univ Bochum, Zool Parasitol Grp, Bochum, Germany. [Rivera-Pomar, Rolando; Diambra, Luis] Univ Nacl La Plata, Ctr Reg Estudios Genom, Florencio Varela, Argentina. [Rivera-Pomar, Rolando] Univ Nacl Noroeste Buenos Aires, Ctr Bioinvest, Pergamino, Argentina. RP Ribeiro, JMC (reprint author), NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20892 USA. EM jribeiro@niaid.nih.gov; gbraz@iq.ufrj.br; pedro@bioqmed.ufrj.br RI Alves-Bezerra, Michele/B-4662-2014; Koerich, Leonardo/J-7004-2014; Melo, Ana C. A./K-1048-2013; Diambra, Luis/F-6319-2015; Lazoski, Cristiano/H-6192-2013; Araujo, Helena/D-7149-2013; Ribeiro, Jose/J-7011-2015; Dias, Felipe/L-7390-2013; Majerowicz, David/B-5361-2016; Silber, Ariel/O-6951-2015 OI Ribeiro, Jose/0000-0002-9107-0818; Oliveira, Pedro/0000-0003-0307-354X; Alves-Bezerra, Michele/0000-0003-4430-6434; Silber, Ariel/0000-0003-4528-4732; Melo, Ana C. A./0000-0003-0686-7089; Diambra, Luis/0000-0001-8052-4880; Araujo, Helena/0000-0003-0371-9523; Dias, Felipe/0000-0003-2074-1052; Majerowicz, David/0000-0001-7916-5315; FU Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases; CAPES; CNPq; FAPESP; FAPERJ; FAPEMIG; PRPq/UFMG; ANPCyT [PICT-2010-0135]; UNNOBA [PFCI-512/12]; Max Planck Society Partner Laboratory Program; INBEQMeDI; Wallonie-Bruxelles International (WBI)/Fundacao Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); WHO FX JMCR was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. GRCB, FAG, ACAM, DS, SaB and SeB were supported by CAPES; CP, HMA, MHFS, PLO, GRCB, ACAM, AMS and FAG were supported by CNPq; AMS, ACP, AST, CF and WRT were supported by FAPESP; ACAM, FAG, CP, HMA, MHFS, PLO and GRCB were supported by FAPERJ; RNA was supported by FAPEMIG and PRPq/UFMG; RRP was supported by grants ANPCyT PICT-2010-0135, UNNOBA PFCI-512/12 and by the Max Planck Society Partner Laboratory Program; AMS was supported by a grant from INBEQMeDI; DS, SaB and SeB were supported by the Wallonie-Bruxelles International (WBI)/Fundacao Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) bilateral cooperation agreement; CP was also supported by a grant from the WHO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 235 TC 40 Z9 41 U1 4 U2 37 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2014 VL 8 IS 1 AR e2594 DI 10.1371/journal.pntd.0002594 PG 31 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AJ8SI UT WOS:000337977300008 PM 24416461 ER PT J AU Xiao, H Tian, HY Gao, LD Liu, HN Duan, LS Basta, N Cazelles, B Li, XJ Lin, XL Wu, HW Chen, BY Yang, HS Xu, B Grenfell, B AF Xiao, Hong Tian, Huai-Yu Gao, Li-Dong Liu, Hai-Ning Duan, Liang-Song Basta, Nicole Cazelles, Bernard Li, Xiu-Jun Lin, Xiao-Ling Wu, Hong-Wei Chen, Bi-Yun Yang, Hui-Suo Xu, Bing Grenfell, Bryan TI Animal Reservoir, Natural and Socioeconomic Variations and the Transmission of Hemorrhagic Fever with Renal Syndrome in Chenzhou, China, 2006-2010 SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID HANTAVIRUS PULMONARY SYNDROME; REPUBLIC-OF-CHINA; NEPHROPATHIA-EPIDEMICA; TEMPORAL DYNAMICS; VARIABILITY; CLIMATE; DISEASE; VIRUS; VOLES; RISK AB Background: China has the highest incidence of hemorrhagic fever with renal syndrome (HFRS) worldwide. Reported cases account for 90% of the total number of global cases. By 2010, approximately 1.4 million HFRS cases had been reported in China. This study aimed to explore the effect of the rodent reservoir, and natural and socioeconomic variables, on the transmission pattern of HFRS. Methodology/Principal Findings: Data on monthly HFRS cases were collected from 2006 to 2010. Dynamic rodent monitoring data, normalized difference vegetation index (NDVI) data, climate data, and socioeconomic data were also obtained. Principal component analysis was performed, and the time-lag relationships between the extracted principal components and HFRS cases were analyzed. Polynomial distributed lag (PDL) models were used to fit and forecast HFRS transmission. Four principal components were extracted. Component 1 (F1) represented rodent density, the NDVI, and monthly average temperature. Component 2 (F2) represented monthly average rainfall and monthly average relative humidity. Component 3 (F3) represented rodent density and monthly average relative humidity. The last component (F4) represented gross domestic product and the urbanization rate. F2, F3, and F4 were significantly correlated, with the monthly HFRS incidence with lags of 4 months (r = -0.289, P < 0.05), 5 months (r = -0.523, P < 0.001), and 0 months (r = -0.376, P < 0.01), respectively. F1 was correlated with the monthly HFRS incidence, with a lag of 4 months (r = 0.179, P = 0.192). Multivariate PDL modeling revealed that the four principal components were significantly associated with the transmission of HFRS. Conclusions: The monthly trend in HFRS cases was significantly associated with the local rodent reservoir, climatic factors, the NDVI, and socioeconomic conditions present during the previous months. The findings of this study may facilitate the development of early warning systems for the control and prevention of HFRS and similar diseases. C1 [Xiao, Hong; Liu, Hai-Ning; Lin, Xiao-Ling] Hunan Normal Univ, Coll Resources & Environm Sci, Changsha, Hunan, Peoples R China. [Tian, Huai-Yu; Xu, Bing] Beijing Normal Univ, Coll Global Change & Earth Syst Sci, Beijing 100875, Peoples R China. [Tian, Huai-Yu; Xu, Bing] Tsinghua Univ, Sch Environm, Beijing 100084, Peoples R China. [Gao, Li-Dong; Chen, Bi-Yun] Hunan Prov Ctr Dis Control & Prevent, Changsha, Hunan, Peoples R China. [Duan, Liang-Song; Wu, Hong-Wei] Chenzhou Municipal Ctr Dis Control & Prevent, Chenzhou, Peoples R China. [Basta, Nicole; Grenfell, Bryan] Princeton Univ, Dept Ecol & Evolut Biol, Princeton, NJ 08544 USA. [Basta, Nicole; Grenfell, Bryan] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Cazelles, Bernard] UPMC, ENS, UMR 7625, Paris, France. [Cazelles, Bernard] UPMC, IRD, UMI 209, UMMISCO, Bondy, France. [Li, Xiu-Jun; Yang, Hui-Suo] Shandong Univ, Sch Publ Hlth, Jinan 250100, Peoples R China. Ctr Dis Control & Prevent Beijing Mil Reg, Beijing, Peoples R China. RP Xiao, H (reprint author), Hunan Normal Univ, Coll Resources & Environm Sci, Changsha, Hunan, Peoples R China. EM xiaohong.hnnu@gmail.com; gldlj@hotmail.com RI Xu, Bing/C-7732-2015; Cazelles, Bernard/B-1572-2013; Tian, Huaiyu/G-1934-2016 OI Cazelles, Bernard/0000-0002-7972-361X; FU Construct Program of the Key Discipline in Hunan Province, China; Ministry of Science and Technology, China, National Research Program [2010CB530300, 2012CB955501, 2012AA12A407]; Science and Technology Directorate, Department of Homeland Security [HSHQDC-12-C-00058]; Bill and Melinda Gates Foundation; RAPIDD program of the Science and Technology Directorate, U.S. Department of Homeland Security; Fogarty International Center, NIH; NIH Director's Early Independence Award [DP5OD009162]; European Commission [282-378]; Scientific Research Fund of Hunan Provincial Education Department [13A051] FX This research was supported by the Construct Program of the Key Discipline in Hunan Province, China. Ministry of Science and Technology, China, National Research Program (2010CB530300, 2012CB955501, 2012AA12A407), the National Natural Science Foundation of China (41271099), Scientific Research Fund of Hunan Provincial Education Department (13A051). BG is supported by the Science and Technology Directorate, Department of Homeland Security contract HSHQDC-12-C-00058 and the Bill and Melinda Gates Foundation. BG and NB are also supported by the RAPIDD program of the Science and Technology Directorate, U.S. Department of Homeland Security, and the Fogarty International Center, NIH. NB is supported by the NIH Director's Early Independence Award DP5OD009162 (Office of the Director and the National Institute of Dental and Craniofacial Research). BC was partially supported by the European Commission Seventh Framework Programme (FP7/2007-2013) for the DENFREE project under grant agreement no. 282-378. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 12 Z9 12 U1 2 U2 20 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2014 VL 8 IS 1 AR e2615 DI 10.1371/journal.pntd.0002615 PG 8 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AJ8SI UT WOS:000337977300020 PM 24421910 ER PT J AU Veselovsky, AV Zharkova, MS Poroikov, VV Nicklaus, MC AF Veselovsky, A. V. Zharkova, M. S. Poroikov, V. V. Nicklaus, M. C. TI Computer-aided design and discovery of protein-protein interaction inhibitors as agents for anti-HIV therapy SO SAR AND QSAR IN ENVIRONMENTAL RESEARCH LA English DT Article DE HIV-1; protein-protein interactions; inhibitors; computer-aided design & discovery; drug target ID SMALL-MOLECULE INHIBITORS; REVERSE-TRANSCRIPTASE DIMERIZATION; PEPTIDE INHIBITORS; DRUG DISCOVERY; ENVELOPE GLYCOPROTEIN; P53-MDM2 INTERACTION; SYNTHETIC PEPTIDES; ENTRY INHIBITORS; CCR5 ANTAGONISTS; RECENT PROGRESS AB Protein-protein interactions (PPI) are involved in most of the essential processes that occur in organisms. In recent years, PPI have become the object of increasing attention in drug discovery, particularly for anti-HIV drugs. Although the use of combinations of existing drugs, termed highly active antiretroviral therapy (HAART), has revolutionized the treatment of HIV/AIDS, problems with these agents, such as the rapid emergence of drug-resistant HIV-1 mutants and serious adverse effects, have highlighted the need for further discovery of new drugs and new targets. Numerous investigations have shown that PPI play a key role in the virus's life cycle and that blocking or modulating them has a significant therapeutic potential. Here we summarize the recent progress in computer-aided design of PPI inhibitors, mainly focusing on the selection of the drug targets (HIV enzymes and virus entry machinery) and the utilization of peptides and small molecules to prevent a variety of protein-protein interactions (viral-viral or viral-host) that play a vital role in the progression of HIV infection. C1 [Veselovsky, A. V.; Zharkova, M. S.; Poroikov, V. V.] Russian Acad Med Sci, Orekhovich Inst Biomed Chem, Moscow, Russia. [Nicklaus, M. C.] NCI, NIH, Frederick, MD 21701 USA. RP Veselovsky, AV (reprint author), Russian Acad Med Sci, Orekhovich Inst Biomed Chem, Moscow, Russia. EM veselov@ibmh.msk.su RI Nicklaus, Marc/N-4183-2014; Veselovsky, Alexander/I-3556-2012; Poroikov, Vladimir/O-2769-2013; OI Veselovsky, Alexander/0000-0001-6362-7757; Poroikov, Vladimir/0000-0001-7937-2621; Nicklaus, Marc/0000-0002-4775-7030 FU Russian Foundation of Basic Research [13-04-91455_NIH-a] FX This paper was presented at the 7th CMTPI conference in Seoul, 8-12 October 2013. This work was supported by Russian Foundation of Basic Research [grant number 13-04-91455_NIH-a]. NR 81 TC 4 Z9 5 U1 1 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1062-936X EI 1029-046X J9 SAR QSAR ENVIRON RES JI SAR QSAR Environ. Res. PY 2014 VL 25 IS 6 BP 457 EP 471 DI 10.1080/1062936X.2014.898689 PG 15 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications; Environmental Sciences; Mathematical & Computational Biology; Toxicology SC Chemistry; Computer Science; Environmental Sciences & Ecology; Mathematical & Computational Biology; Toxicology GA AJ8GJ UT WOS:000337940500003 PM 24716798 ER PT S AU Quinn, M Ramamoorthy, S Cidlowski, JA AF Quinn, Matthew Ramamoorthy, Sivapriya Cidlowski, John A. BE Cutolo, M Straub, RH Masi, AT Bijlsma, JWJ TI Sexually dimorphic actions of glucocorticoids: beyond chromosomes and sex hormones SO STEROIDS IN NEUROENDOCRINE IMMUNOLOGY AND THERAPY OF RHEUMATIC DISEASES I SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 5th International Conference on the Neuroendocrine Immune Basis of the Rheumatic Diseases (NEIRD) CY OCT 01-03, 2013 CL Genoa, ITALY DE glucocorticoid receptor; glucocorticoids; sexual dimorphism; sex hormone ID GENDER-DIFFERENCES; GENE-EXPRESSION; GROWTH-HORMONE; DISEASE; AGE; METABOLISM; MICE; INACTIVATION; PREVALENCE; FEMALES AB Sexual dimorphism is a well-documented phenomenon that is observed at all levels of the animal kingdom. Historically, sex hormones (testosterone and estrogen) have been implicated as key players in a wide array of pathologies displaying sexual dimorphism in their etiology and progression. While these hormones clearly contribute to sexually dimorphic diseases, other factors may be involved in this phenomenon as well. In particular, the stress hormone cortisol exerts differential effects in both males and females. The underlying molecular basis for the sexually dimorphic actions of glucocorticoids is unknown but clearly important to understand, since synthetic glucocorticoids are the most widely prescribed medication for the treatment of chronic inflammatory diseases and hematological cancers in humans. C1 [Quinn, Matthew; Ramamoorthy, Sivapriya; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, US Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, MD F3-07,POB 12233, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov NR 41 TC 12 Z9 12 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2014 VL 1317 BP 1 EP 6 DI 10.1111/nyas.12425 PG 6 WC Endocrinology & Metabolism; Immunology; Rheumatology SC Endocrinology & Metabolism; Immunology; Rheumatology GA BA7WL UT WOS:000337808900002 PM 24739020 ER PT S AU Nicolaides, NC Charmandari, E Chrousos, GP Kino, T AF Nicolaides, Nicolas C. Charmandari, Evangelia Chrousos, George P. Kino, Tomoshige BE Cutolo, M Straub, RH Masi, AT Bijlsma, JWJ TI Circadian endocrine rhythms: the hypothalamic-pituitary-adrenal axis and its actions SO STEROIDS IN NEUROENDOCRINE IMMUNOLOGY AND THERAPY OF RHEUMATIC DISEASES II SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 5th International Conference on the Neuroendocrine Immune Basis of the Rheumatic Diseases (NEIRD) CY OCT 01-03, 2013 CL Genoa, ITALY DE HPA axis; circadian clock system; glucocorticoids; glucocorticoid receptor; acetylation ID HUMAN GLUCOCORTICOID-RECEPTOR; RHEUMATOID-ARTHRITIS; PERIPHERAL-TISSUES; METABOLIC SYNDROME; SHIFT WORK; TRANSCRIPTIONAL ACTIVITY; MEDIATED REGULATION; GENE-EXPRESSION; CLOCK; MECHANISMS AB The stress system effectively restores the internal balance-or homeostasis-of living organisms in the face of random external or internal changes, the stressors. This highly complex system helps organisms to provide a series of neuroendocrine responses to stressors-the stress response-through coordinated activation of the hypothalamic-pituitary-adrenal (HPA) axis and the locus coeruleus/norepinephrine autonomic nervous systems. In addition to stressors, life is influenced by daily light/dark changes due to the 24-h rotation of Earth. To adjust to these recurrent day/night cycles, the biological clock system employs the heterodimer of transcription factors circadian locomotor output cycle kaput/brain-muscle-arnt-like protein 1 (CLOCK/BMAL1), along with a set of other transcription factors, to regulate the circadian pattern of gene expression. Interestingly, the stress system, through the HPA axis, communicates with the clock system; therefore, any uncoupling or dysregulation could potentially cause several disorders, such as metabolic, autoimmune, and mood disorders. In this review, we discuss the biological function of the two systems, their interactions, and the clinical implications of their dysregulation or uncoupling. C1 [Nicolaides, Nicolas C.; Charmandari, Evangelia; Chrousos, George P.] Univ Athens, Aghia Sophia Childrens Hosp, Sch Med, Dept Pediat 1,Div Endocrinol Metab & Diabet, Athens, Greece. [Nicolaides, Nicolas C.; Charmandari, Evangelia; Chrousos, George P.] Biomed Res Fdn Acad Athens, Clin Res Ctr, Div Endocrinol & Metab, Athens 11527, Greece. [Chrousos, George P.] King Abdulaziz Univ, King Fahd Med Res Ctr, Saudi Diabet Study Res Grp, Jeddah 21413, Saudi Arabia. [Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. RP Nicolaides, NC (reprint author), Biomed Res Fdn Acad Athens, Clin Res Ctr, Div Endocrinol & Metab, 4 Soranou Tou Efessiou St, Athens 11527, Greece. EM nnicolaides@bioacademy.gr RI Charmandari, Evangelia/B-6701-2011 FU European Union (European Social Fund, ESF); intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland FX This work was supported by (1) the European Union (European Social Fund, ESF) and Greek national funds through the operational program "Education and Lifelong Learning" of the National Strategic Reference Framework Research Funding Program THALIS, University of Athens, Athens, Greece; and (2) the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. NR 77 TC 29 Z9 29 U1 5 U2 23 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2014 VL 1318 BP 71 EP 80 DI 10.1111/nyas.12464 PG 10 WC Endocrinology & Metabolism; Immunology; Rheumatology SC Endocrinology & Metabolism; Immunology; Rheumatology GA BA7XF UT WOS:000337847000010 PM 24890877 ER PT J AU Mccoy, BN Maiga, O Schwan, TG AF McCoy, Brandi N. Maiga, Ousmane Schwan, Tom G. TI Detection of Borrelia theileri in Rhipicephalus geigyi from Mali SO TICKS AND TICK-BORNE DISEASES LA English DT Article DE Bovine borreliosis; Tick; Boophilus; West Africa; Spirochete ID BORNE RELAPSING FEVER; BOOPHILUS-MICROPLUS; LYME-DISEASE; WEST-AFRICA; CATTLE TICK; TRANSMISSION; SPIROCHETE AB Disease burden within cattle is a concern around the world. Bovine borreliosis, one such disease, is caused by the spirochete Borrelia theileri transmitted by the bite of an infected Rhipicephalus (Boophilus) species tick. A number of species within the genus are capable of transmitting the agent and are found on multiple continents. Cattle in the West African nation of Mali are infested with four species of Rhipicephalus ticks of the subgenus Boophilus: Rhipicephalus annulatus, Rhipicephalus microplus, Rhipicephalus decoloratus, and Rhipicephalus geigyi. To date, no reports of B. theileri within Mali have been documented. We tested 184 Rhipicephalus spp. ticks by PCR that were removed from cattle at a market near Bamako, Mali. One tick, R. geigyi, was positive for B. theileri, which confirmed the presence of this spirochete in Mali. Published by Elsevier GmbH. C1 [McCoy, Brandi N.; Schwan, Tom G.] NIAID, Rocky Mt Lab, Lab Zoonot Pathogens, NIH, Hamilton, MT 59840 USA. [Maiga, Ousmane] Univ Sci Tech & Technol Bamako, Malaria Res & Training Ctr, Bamako, Mali. RP Mccoy, BN (reprint author), NIAID, Rocky Mt Lab, Lab Zoonot Pathogens, NIH, Hamilton, MT 59840 USA. EM brandi.williamson@nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases of the National Institutes of Health FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases of the National Institutes of Health. We thank Bob Fischer, Sandra Stewart, and Philip Stewart for reviewing the manuscript; Nafomon Sogoba and Sekou F. Traore for field and administrative help; and Sory Coulibaly for allowing us to collect ticks at the cattle markets. NR 19 TC 9 Z9 9 U1 0 U2 4 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 1877-959X EI 1877-9603 J9 TICKS TICK-BORNE DIS JI Ticks Tick-Borne Dis. PY 2014 VL 5 IS 4 BP 401 EP 403 DI 10.1016/j.ttbdis.2014.01.007 PG 3 WC Infectious Diseases; Microbiology; Parasitology SC Infectious Diseases; Microbiology; Parasitology GA AJ9BO UT WOS:000338002000007 PM 24709337 ER PT S AU Pecon-Slattery, J AF Pecon-Slattery, Jill BE Lewin, HA Roberts, RM TI Recent Advances in Primate Phylogenomics SO ANNUAL REVIEW OF ANIMAL BIOSCIENCES, VOL 2 SE Annual Review of Animal Biosciences LA English DT Article; Book Chapter DE taxonomy; evolution; adaptation; genomics; human; phylogeny ID NEW-WORLD PRIMATES; AYE DAUBENTONIA-MADAGASCARIENSIS; COPY NUMBER VARIATION; GREAT APE; MOLECULAR PHYLOGENY; DIVERGENCE TIMES; HUMAN-EVOLUTION; Y-CHROMOSOME; STRUCTURAL VARIATION; POPULATION HISTORY AB The world of primate genomics is expanding rapidly in new and exciting ways owing to lowered costs and new technologies in molecular methods and bioinformatics. The primate order is composed of 78 genera and 478 species, including human. Taxonomic inferences are complex and likely a consequence of ongoing hybridization, introgression, and reticulate evolution among closely related taxa. Recently, we applied large-scale sequencing methods and extensive taxon sampling to generate a highly resolved phylogeny that affirms, reforms, and extends previous depictions of primate speciation. The next stage of research uses this phylogeny as a foundation for investigating genome content, structure, and evolution across primates. Ongoing and future applications of a robust primate phylogeny are discussed, highlighting advancements in adaptive evolution of genes and genomes, taxonomy and conservation management of endangered species, next-generation genomic technologies, and biomedicine. C1 [Pecon-Slattery, Jill] NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Pecon-Slattery, J (reprint author), Smithsonian Conservat Biol Inst, Natl Zool Pk, Front Royal, VA 22630 USA. EM SlatteryJP@si.edu NR 161 TC 4 Z9 4 U1 8 U2 58 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 2165-8102 BN 978-0-8243-0002-9 J9 ANNU REV ANIM BIOSCI PY 2014 VL 2 BP 41 EP 63 DI 10.1146/annurev-animal-022513-114217 PG 23 WC Biotechnology & Applied Microbiology; Veterinary Sciences; Zoology SC Biotechnology & Applied Microbiology; Veterinary Sciences; Zoology GA BA4OC UT WOS:000336052100004 PM 25384134 ER PT S AU Averbeck, BB O'Sullivan, SS Djamshidian, A AF Averbeck, B. B. O'Sullivan, S. S. Djamshidian, A. BE Cannon, TD Widiger, T TI Impulsive and Compulsive Behaviors in Parkinson's Disease SO ANNUAL REVIEW OF CLINICAL PSYCHOLOGY, VOL 10 SE Annual Review of Clinical Psychology LA English DT Article; Book Chapter DE impulsive compulsive behaviors; Parkinson's disease; neuropsychiatry; dopamine agonists ID DEEP BRAIN-STIMULATION; DOPAMINE DYSREGULATION SYNDROME; AGONIST WITHDRAWAL SYNDROME; PLACEBO-CONTROLLED TRIAL; CONTROL DISORDERS; REFLECTION-IMPULSIVITY; SUBTHALAMIC NUCLEUS; MOVEMENT-DISORDERS; SPECTRUM BEHAVIORS; COGNITIVE FUNCTION AB Impulsive-compulsive behaviors (ICBs) in Parkinson's disease (PD) are a common and devastating side effect of dopamine replacement therapy. In this review we describe the phenomenology, prevalence, and risk factors of patients with PD. Results of behavioral studies assessing the neuropsychological profile of patients with PD emphasize that the ICBs, which are behavioral addictions, are not hedonically motivated. Rather, other factors such as the inability to cope with uncertainty may be triggering ICBs. New insights from functional imaging studies, strengthening the incentive salience hypothesis, are discussed, and therapeutic guidelines for the management of ICBs in PD are given. C1 [Averbeck, B. B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [O'Sullivan, S. S.] Natl Univ Ireland Univ Coll Cork, Dept Neurol, Cork Univ Hosp, Cork, Ireland. [Djamshidian, A.] Univ London, Reta Lila Weston Inst Neurol Studies, London, England. RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 9, Bethesda, MD 20892 USA. EM atbin.djamshidian@gmail.com FU Intramural NIH HHS [ZIA MH002928-05] NR 161 TC 10 Z9 10 U1 9 U2 16 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1548-5943 BN 978-0-8243-3910-4 J9 ANNU REV CLIN PSYCHO JI Annu. Rev. Clin. Psychol. PY 2014 VL 10 BP 553 EP 580 DI 10.1146/annurev-clinpsy-032813-153705 PG 28 WC Psychology, Clinical; Psychology SC Psychology GA BA4XX UT WOS:000336428200022 PM 24313567 ER PT S AU Paul, WE AF Paul, William E. BE Littman, DR Yokoyama, WM TI Endless Fascination SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 32 SE Annual Review of Immunology LA English DT Review; Book Chapter DE cytokines; AIDS; antibody specificity; Th2 cells; major histocompatibility complex; immune response genes; interleukin-4 ID STIMULATORY FACTOR-I; CD4+ T-CELLS; HAPTEN ANTIBODY RESPONSES; B-CELL; IMMUNE RESPONSES; LYMPHOCYTE PROLIFERATION; PRODUCE INTERLEUKIN-4; ANTIGEN RECOGNITION; MOUSE LYMPHOCYTES; INTERFERON-GAMMA AB Each of us fortunate enough to have had a career in experimental science has a tale to tell, often one with surprising twists and turns, full of lessons that can help guide those embarking on a similar journey. At the very least, a well-written recounting of a career can be entertaining. I offer my memory's version of my career in immunology and hope the readers will find it of value or at least of interest. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wpaul@niaid.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [Z01-AI000968-08, Z01-AI000926-11, Z01-AI000493-27, Z01-AI000969-08] NR 65 TC 1 Z9 1 U1 1 U2 9 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3032-3 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2014 VL 32 BP 1 EP 24 DI 10.1146/annurev-immunol-032713-120247 PG 24 WC Immunology SC Immunology GA BA4XV UT WOS:000336427400001 PM 24161002 ER PT S AU Crompton, PD Moebius, J Portugal, S Waisberg, M Hart, G Garver, LS Miller, LH Barillas, C Pierce, SK AF Crompton, Peter D. Moebius, Jacqueline Portugal, Silvia Waisberg, Michael Hart, Geoffrey Garver, Lindsey S. Miller, Louis H. Barillas, Carolina Pierce, Susan K. BE Littman, DR Yokoyama, WM TI Malaria Immunity in Man and Mosquito: Insights into Unsolved Mysteries of a Deadly Infectious Disease SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 32 SE Annual Review of Immunology LA English DT Review; Book Chapter DE malaria; mosquito immunity; human immunity; human adaptive immunity; human innate immunity ID MEMORY B-CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; MURINE CEREBRAL MALARIA; PLASMODIUM-FALCIPARUM SPOROZOITES; TUMOR-NECROSIS-FACTOR; NATURAL-KILLER-CELLS; CD8(+) T-CELLS; BRAIN ENDOTHELIAL-CELLS; ANOPHELES-GAMBIAE; AUTOIMMUNE-DISEASE AB Malaria is a mosquito-borne disease caused by parasites of the obligate intracellular Apicomplexa phylum the most deadly of which, Plasmodium falciparum, prevails in Africa. Malaria imposes a huge health burden on the world's most vulnerable populations, claiming the lives of nearly one million children and pregnant women each year. Although there is keen interest in eradicating malaria, we do not yet have the necessary tools to meet this challenge, including an effective malaria vaccine and adequate vector control strategies. Here we review what is known about the mechanisms at play in immune resistance to malaria in both the human and mosquito hosts at each step in the parasite's complex life cycle with a view toward developing the tools that will contribute to the prevention of disease and death and, ultimately, to the goal of malaria eradication. In so doing, we hope to inspire immunologists to participate in defeating this devastating disease. C1 [Crompton, Peter D.; Moebius, Jacqueline; Portugal, Silvia; Waisberg, Michael; Hart, Geoffrey; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Garver, Lindsey S.; Miller, Louis H.; Barillas, Carolina] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Crompton, PD (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM spierce@niaid.nih.gov RI Crompton, Peter/N-1130-2016; OI Garver, Lindsey/0000-0003-2893-0130 FU Intramural NIH HHS [ZIA AI001064-06] NR 228 TC 53 Z9 53 U1 2 U2 36 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3032-3 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2014 VL 32 BP 157 EP 187 DI 10.1146/annurev-immunol-032713-120220 PG 31 WC Immunology SC Immunology GA BA4XV UT WOS:000336427400006 PM 24655294 ER PT S AU Nayak, D Roth, TL McGavern, DB AF Nayak, Debasis Roth, Theodore L. McGavern, Dorian B. BE Littman, DR Yokoyama, WM TI Microglia Development and Function SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 32 SE Annual Review of Immunology LA English DT Review; Book Chapter DE brain; innate immunity; myeloid cells; two-photon ID CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE PATHOLOGY; HUMAN-IMMUNODEFICIENCY-VIRUS; COLONY-STIMULATING FACTOR-1; HIPPOCAMPAL SLICE CULTURES; HEMATOPOIETIC STEM-CELLS; SEQUENCE-BINDING-PROTEIN; NECROSIS-FACTOR-ALPHA; CNS MYELOID CELLS; OP OP MOUSE AB Proper development and function of the mammalian central nervous system (CNS) depend critically on the activity of parenchymal sentinels referred to as microglia. Although microglia were first described as ramified brain-resident phagocytes, research conducted over the past century has expanded considerably upon this narrow view and ascribed many functions to these dynamic CNS inhabitants. Microglia are now considered among the most versatile cells in the body, possessing the capacity to morphologically and functionally adapt to their ever-changing surroundings. Even in a resting state, the processes of microglia are highly dynamic and perpetually scan the CNS. Microglia are in fact vital participants in CNS homeostasis, and dysregulation of these sentinels can give rise to neurological disease. In this review, we discuss the exciting developments in our understanding of microglial biology, from their developmental origin to their participation in CNS homeostasis and pathophysiological states such as neuropsychiatric disorders, neurodegeneration, sterile injury responses, and infectious diseases. We also delve into the world of microglial dynamics recently uncovered using real-time imaging techniques. C1 [Nayak, Debasis; Roth, Theodore L.; McGavern, Dorian B.] NINDS, NIH, Bethesda, MD 20892 USA. RP Nayak, D (reprint author), NINDS, NIH, Bethesda, MD 20892 USA. EM mcgavernd@mail.nih.gov OI McGavern, Dorian/0000-0001-9568-545X; Roth, Theodore/0000-0002-3970-9573 FU Intramural NIH HHS [ZIA NS003112-07] NR 219 TC 85 Z9 87 U1 5 U2 39 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3032-3 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2014 VL 32 BP 367 EP 402 DI 10.1146/annurev-immunol-032713-120240 PG 36 WC Immunology SC Immunology GA BA4XV UT WOS:000336427400012 PM 24471431 ER PT S AU Browne, SK AF Browne, Sarah K. BE Littman, DR Yokoyama, WM TI Anticytokine Autoantibody-Associated Immunodeficiency SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 32 SE Annual Review of Immunology LA English DT Review; Book Chapter DE anticytokine autoantibodies; immunodeficiency; interferon-gamma; IFN-gamma; granulocyte macrophage-colony stimulating factor; GM-CSF; interleukin-17; IL-17 ID PULMONARY ALVEOLAR PROTEINOSIS; COLONY-STIMULATING FACTOR; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHRONIC MUCOCUTANEOUS CANDIDIASIS; ANTI-CYTOKINE AUTOANTIBODIES; RED-CELL APLASIA; INTERFERON-ALPHA ANTIBODIES; MYASTHENIA-GRAVIS PATIENTS; MYCOBACTERIUM-AVIUM COMPLEX; IFN-GAMMA AUTOANTIBODY AB Anticytokine autoantibodies are an emerging mechanism of disease in previously healthy adults. Patients with these syndromes demonstrate a unique infectious phenotype associated with neutralizing autoantibodies that target a specific cytokine. Examples include anti-interferon (IFN)-gamma autoantibodies and disseminated nontuberculous mycobacteria; anti-granulocyte macrophage colony-stimulating factor autoantibodies and cryptococcal meningitis; anti-interleukin (IL)-6 autoantibodies and staphylococcal skin infection; and anti-IL-17A, anti-IL-17F, or anti-IL-22 autoantibodies and mucocutaneous candidiasis in the setting of either APECED (autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy syndrome) or thymoma. Other anticytokine autoantibodies may contribute to an infectious phenotype such as anti-granulocyte colony stimulating factor and anti-IFN alpha autoantibodies, although the strength of the association is less clear. Their identification not only affects disease management but also may uncover key mechanisms of host defense against specific organisms. Furthermore, it raises the possibility that currently idiopathic diseases will someday be explained by a yet unidentified anticytokine autoantibody. This review focuses on the current understanding, both clinical and mechanistic, of anticytokine autoantibody-associated immunodeficiency. C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Browne, SK (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM brownesa@niaid.nih.gov FU Intramural NIH HHS NR 151 TC 25 Z9 25 U1 1 U2 7 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3032-3 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2014 VL 32 BP 635 EP 657 DI 10.1146/annurev-immunol-032713-120222 PG 23 WC Immunology SC Immunology GA BA4XV UT WOS:000336427400021 PM 24499273 ER PT S AU Jesus, AA Goldbach-Mansky, R AF Jesus, Adriana A. Goldbach-Mansky, Raphaela BE Caskey, CT TI IL-1 Blockade in Autoinflammatory Syndromes SO ANNUAL REVIEW OF MEDICINE, VOL 65 SE Annual Review of Medicine LA English DT Review; Book Chapter DE anakinra; rilonacept; canakinumab; interleukin-1; hereditary periodic; fever syndromes ID FAMILIAL MEDITERRANEAN FEVER; INTERLEUKIN-1 RECEPTOR ANTAGONIST; JUVENILE IDIOPATHIC ARTHRITIS; PLACEBO-CONTROLLED TRIAL; ONSET STILLS-DISEASE; TERM-FOLLOW-UP; CHRONIC NONBACTERIAL OSTEOMYELITIS; HYPERIMMUNOGLOBULINEMIA-D SYNDROME; SYNDROME PAPA SYNDROME; ACUTE GOUTY-ARTHRITIS AB Monogenic autoinflammatory syndromes present with excessive systemic inflammation including fever, rashes, arthritis, and organ-specific inflammation and are caused by defects in single genes encoding proteins that regulate innate inflammatory pathways. Pathogenic variants in two interleukin-1 (IL-1)-regulating genes, NLRP3 and IL1RN, cause two severe and early-onset autoinflammatory syndromes, CAPS (cryopyrin associated periodic syndromes) and DIRA (deficiency of IL-1 receptor antagonist). The discovery of the mutations that cause CAPS and DIRA led to clinical and basic research that uncovered the key role of IL-1 in an extended spectrum of immune dysregulatory conditions. NLRP3 encodes cryopyrin, an intracellular "molecular sensor" that forms a multimolecular platform, the NLRP3 inflammasome, which links " danger recognition" to the activation of the proinflammatory cytokine IL-1 beta The success and safety profile of drugs targeting IL -1 in the treatment of CAPS and DIRA have encouraged their wider use in other autoinflammatory syndromes including the classic hereditary periodic fever syndromes (familial Mediterranean fever, TNF receptor-associated periodic syndrome, and hyperimmunoglobulinemia D with periodic fever syndrome) and additional immune dysregulatory conditions that are not genetically well defined, including Still's, Behcet's, and Schnitzler diseases. The fact that the accumulation of metabolic substrates such as monosodium urate, ceramide, cholesterol, and glucose can trigger the NLRP3 inflammasome connects metabolic stress to IL-1 beta-mediated inflammation and provides a rationale for therapeutically targeting IL-1 in prevalent diseases such as gout, diabetes mellitus, and coronary artery disease. C1 [Jesus, Adriana A.; Goldbach-Mansky, Raphaela] NIAMSD, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20982 USA. RP Jesus, AA (reprint author), NIAMSD, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20982 USA. EM goldbacr@mail.nih.gov FU Intramural NIH HHS [ZIA AR041138-11] NR 172 TC 54 Z9 56 U1 0 U2 11 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0565-9 J9 ANNU REV MED JI Annu. Rev. Med. PY 2014 VL 65 BP 223 EP + DI 10.1146/annurev-med-061512-150641 PG 50 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BA4OD UT WOS:000336053000015 PM 24422572 ER PT S AU Tobian, AAR Kacker, S Quinn, TC AF Tobian, Aaron A. R. Kacker, Seema Quinn, Thomas C. BE Caskey, CT TI Male Circumcision: A Globally Relevant but Under-Utilized Method for the Prevention of HIV and Other Sexually Transmitted Infections SO ANNUAL REVIEW OF MEDICINE, VOL 65 SE Annual Review of Medicine LA English DT Review; Book Chapter DE AIDS; herpes simplex virus type 2 (HSV-2); human papillomavirus (HPV); cervical cancer; bacterial vaginosis ID RISK HUMAN-PAPILLOMAVIRUS; VIRUS TYPE-2 INFECTION; ADULT MALE CIRCUMCISION; SUB-SAHARAN AFRICA; RANDOMIZED CONTROLLED-TRIAL; POSTTRIAL FOLLOW-UP; FEMALE PARTNERS; UNITED-STATES; NEWBORN CIRCUMCISION; CERVICAL-CANCER AB Randomized trials have demonstrated that male circumcision (MC) reduces heterosexual acquisition of HIV, herpes simplex virus type 2, human papillomavirus (HPV), and genital ulcer disease among men, and it reduces HPV, genital ulcer disease, bacterial vaginosis, and trichomoniasis among female partners. The pathophysiology behind these effects is multifactorial, relying on anatomic and cellular changes. MC is cost effective and potentially cost saving in both the United States and Africa. The World Health Organization and Joint United Nations Program on HIV/AIDS proposed reaching 80% MC coverage in HIV endemic countries, but current rates fall far behind targets. Barriers to scale-up include supply-side and demand-side challenges. In the United States, neonatal MC rates are decreasing, but the American Academy of Pediatrics now recognizes the medical benefits of MC and supports insurance coverage. Although MC is a globally valuable tool to prevent HIV and other sexually transmitted infections, it is underutilized. Further research is needed to address barriers to MC uptake. C1 [Tobian, Aaron A. R.; Kacker, Seema] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. [Tobian, Aaron A. R.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21287 USA. [Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Tobian, AAR (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. EM atobian1@jhmi.edu FU Intramural NIH HHS [Z01 AI000361-25]; NIAID NIH HHS [1K23AI093152-01A1., K23 AI093152] NR 90 TC 16 Z9 18 U1 1 U2 4 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0565-9 J9 ANNU REV MED JI Annu. Rev. Med. PY 2014 VL 65 BP 293 EP 306 DI 10.1146/annurev-med-092412-090539 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BA4OD UT WOS:000336053000019 PM 24111891 ER PT S AU Herzenberg, LA Herzenberg, LA Roederer, M AF Herzenberg, Leonard A. Herzenberg, Leonore A. Roederer, Mario BE Julius, D TI A Conversation with Leonard and Leonore Herzenberg SO ANNUAL REVIEW OF PHYSIOLOGY, VOL 76 SE Annual Review of Physiology LA English DT Review; Book Chapter DE flow cytometry; hybridomas; immunology; technology ID STANFORD; FACS; VIEW AB Leonard and Leonore Herzenberg have left an indelible mark on the fields of immunology and cell biology, both in research and clinical aspects. They are perhaps best known for developing the technologies of fluorescence flow cytometry and hybridomas. Over six decades, they made a number of important and fundamental discoveries in lymphocyte biology by applying these technologies. During this era, they immersed themselves in the sociopolitical environment, interjecting scientific rationale into public discourse about McCarthyism, nuclear fallout, war, genetics, and other politically charged topics. Their unique philosophy has shaped their lives, their science, and ultimately the scientific community. In this Conversation, we explore some of these driving forces and the impact on the laboratory. C1 [Herzenberg, Leonard A.; Herzenberg, Leonore A.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Roederer, Mario] NIH, ImmunoTechnol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Herzenberg, LA (reprint author), Stanford Univ, Dept Genet, Stanford, CA 94305 USA. EM roederer@nih.gov NR 4 TC 2 Z9 2 U1 1 U2 3 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4278 BN 978-0-8243-0376-1 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2014 VL 76 BP 1 EP 20 DI 10.1146/annurev-physiol-021113-170355 PG 20 WC Physiology SC Physiology GA BA4OF UT WOS:000336055000002 PM 23957332 ER PT S AU Wu, LG Hamid, E Shin, W Chiang, HC AF Wu, Ling-Gang Hamid, Edaeni Shin, Wonchul Chiang, Hsueh-Cheng BE Julius, D TI Exocytosis and Endocytosis: Modes, Functions, and Coupling Mechanisms SO ANNUAL REVIEW OF PHYSIOLOGY, VOL 76 SE Annual Review of Physiology LA English DT Review; Book Chapter DE kiss-and-run; compound exocytosis; bulk endocytosis; synaptic plasticity; calmodulin; calcium channels ID SYNAPTIC-VESICLE ENDOCYTOSIS; KISS-AND-RUN; ADRENAL CHROMAFFIN CELLS; FROG NEUROMUSCULAR-JUNCTION; RETINAL BIPOLAR CELLS; DEPENDENT BULK ENDOCYTOSIS; MOTOR-NERVE TERMINALS; CLATHRIN-MEDIATED ENDOCYTOSIS; HIGH-CALCIUM CONCENTRATIONS; READILY RELEASABLE POOL AB Vesicle exocytosis releases content to mediate many biological events, including synaptic transmission essential for brain functions. Following exocytosis, endocytosis is initiated to retrieve exocytosed vesicles within seconds to minutes. Decades of studies in secretory cells reveal three exocytosis modes coupled to three endocytosis modes: (a) full-collapse fusion, in which vesicles collapse into the plasma membrane, followed by classical endocytosis involving membrane invagination and vesicle reformation; (b) kiss-and-run, in which the fusion pore opens and closes; and (c) compound exocytosis, which involves exocytosis of giant vesicles formed via vesicle-vesicle fusion, followed by bulk endocytosis that retrieves giant vesicles. Here we review these exo- and endocytosis modes and their roles in regulating quantal size and synaptic strength, generating synaptic plasticity, maintaining exocytosis, and clearing release sites for vesicle replenishment. Furthermore, we highlight recent progress in understanding how vesicle endocytosis is initiated and is thus coupled to exocytosis. The emerging model is that calcium influx via voltage-dependent calcium channels at the calcium microdomain triggers endocytosis and controls endocytosis rate; calmodulin and synaptotagmin are the calcium sensors; and the exocytosis machinery, including SNARE proteins (synaptobrevin, SNAP25, and syntaxin), is needed to coinitiate endocytosis, likely to control the amount of endocytosis. C1 [Wu, Ling-Gang; Hamid, Edaeni; Shin, Wonchul; Chiang, Hsueh-Cheng] NINDS, Bethesda, MD 20892 USA. RP Wu, LG (reprint author), NINDS, Bethesda, MD 20892 USA. EM wul@ninds.nih.gov; edaeni.hamid@nih.gov FU Intramural NIH HHS [Z01 NS003009-04, Z01 NS003009-05] NR 173 TC 64 Z9 65 U1 11 U2 74 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4278 BN 978-0-8243-0376-1 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2014 VL 76 BP 301 EP 331 DI 10.1146/annurev-physiol-021113-170305 PG 31 WC Physiology SC Physiology GA BA4OF UT WOS:000336055000015 PM 24274740 ER PT J AU Tsai, MY Steffen, BT Guan, WH McClelland, RL Warnick, R McConnell, J Hoefner, DM Remaley, AT AF Tsai, Michael Y. Steffen, Brian T. Guan, Weihua McClelland, Robyn L. Warnick, Russell McConnell, Joseph Hoefner, Daniel M. Remaley, Alan T. TI New Automated Assay of Small Dense Low-Density Lipoprotein Cholesterol Identifies Risk of Coronary Heart Disease The Multi-Ethnic Study of Atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE coronary disease ID NUCLEAR-MAGNETIC-RESONANCE; INCIDENT CARDIOVASCULAR-DISEASE; ARTERY-DISEASE; PARTICLE-SIZE; CAROTID ATHEROSCLEROSIS; LDL CHOLESTEROL; WOMEN; SPECTROSCOPY; SUBCLASSES; INTERVENTION AB Objective-Coronary heart disease (CHD) is the leading cause of death in the United States, yet assessing risk of its development remains challenging. The present study evaluates a new automated assay of small dense low-density lipoprotein cholesterol content (sdLDL-C) and whether sdLDL-C is a risk factor for CHD compared with LDL-C or small LDL particle concentrations derived from nuclear magnetic resonance spectroscopy. Approach and Results-sdLDL-C was measured using a new automated enzymatic method, and small LDL concentrations were obtained by nuclear magnetic resonance in 4387 Multi-Ethnic Study of Atherosclerosis participants. Cox regression analysis estimated hazard ratios for developing CHD for 8.5 years after adjustments for age, race, sex, systolic blood pressure, hypertension medication use, high-density lipoprotein cholesterol, and triglycerides. Elevated sdLDL-C was a risk factor for CHD in normoglycemic individuals. Those in the top sdLDL-C quartile showed higher risk of incident CHD (hazard ratio, 2.41; P=0.0037) compared with those in the bottom quartile and indicated greater CHD risk than the corresponding quartile of LDL-C (hazard ratio, 1.75; P=0.019). The association of sdLDL-C with CHD risk remained significant when LDL-C (<2.57 mmol/L) was included in a multivariate model (hazard ratio, 2.37; P=0.012). Nuclear magnetic resonance-derived small LDL concentrations did not convey a significant risk of CHD. Those with impaired fasting glucose or diabetes mellitus showed higher sdLDL-C and small LDL concentrations but neither was associated with higher CHD risk in these individuals. Conclusions-This new automated method for sdLDL-C identifies risk for CHD that would remain undetected using standard lipid measures, but only in normoglycemic, nondiabetic individuals. C1 [Tsai, Michael Y.; Steffen, Brian T.] Univ Minnesota, Sch Publ Hlth, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Guan, Weihua] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [McClelland, Robyn L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Warnick, Russell; McConnell, Joseph; Hoefner, Daniel M.] Hlth Diagnost Lab Inc, Richmond, VA USA. [Remaley, Alan T.] NHLBI, NIH, Mol Dis Branch, Bethesda, MD 20892 USA. RP Tsai, MY (reprint author), Univ Minnesota, Sch Publ Hlth, Dept Lab Med & Pathol, 420 Delaware St SE,Mayo Mail Code 609, Minneapolis, MN 55455 USA. EM tsaix001@umn.edu FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169] FX This research was supported by contracts, N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute. NR 27 TC 23 Z9 24 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2014 VL 34 IS 1 BP 196 EP + DI 10.1161/ATVBAHA.113.302401 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AJ5NO UT WOS:000337731100026 PM 24233487 ER PT J AU Weiss, PF Chauvin, NA Klink, AJ Localio, R Feudtner, C Jaramillo, D Colbert, RA Sherry, DD Keren, R AF Weiss, Pamela F. Chauvin, Nancy A. Klink, Andrew J. Localio, Russell Feudtner, Chris Jaramillo, Diego Colbert, Robert A. Sherry, David D. Keren, Ron TI Detection of Enthesitis in Children With Enthesitis-Related Arthritis Dolorimetry Compared to Ultrasonography SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID JUVENILE IDIOPATHIC ARTHRITIS; DECREASED PAIN THRESHOLD; CENTRAL-NERVOUS-SYSTEM; QUALITY-OF-LIFE; ANKYLOSING-SPONDYLITIS; RHEUMATOID-ARTHRITIS; POWER DOPPLER; ULTRASOUND; FIBROMYALGIA; AGREEMENT AB Objective. To evaluate the distribution of enthesitis and the accuracy of physical examination with a dolorimeter for the detection of enthesitis in children, using ultrasound (US) assessment as the reference standard. Methods. We performed a prospective cross-sectional study of 30 patients with enthesitis-related arthritis (ERA) and 30 control subjects. The following tendon insertion sites were assessed by standardized physical examination with a dolorimeter and US: common extensor on the lateral humeral epicondyle, common flexor on the medial humeral epicondyle, quadriceps at the superior patella, patellar ligament at the inferior patella, Achilles, and plantar fascia at the calcaneus. Results. Abnormal findings on US were detected most commonly at the insertion of the quadriceps (30% [18 of 60 sites]), common extensor (12% [7 of 60]), and Achilles (10% [6 of 60]) tendons. The intrarater reliability of US (kappa statistic) was 0.78 (95% confidence interval [95% CI] 0.63-0.93), and the interrater reliability was 0.81 (95% CI 0.67-0.95). Tenderness as detected by standardized dolorimeter examination had poor positive predictive value for US-confirmed enthesitis. In comparison to controls, patients with ERA reported more pain and had lower pain thresholds at every site, including control sites (P < 0.001 for all comparisons). The interrater reliability of dolorimeter examination for detection of enthesitis was low (kappa = 0.49 [95% CI 0.33-0.65]). Conclusion. Compared to US, standardized dolorimeter examination for the detection of enthesitis in children has poor accuracy and reliability. The decreased pain threshold of ERA patients likely contributed to the limited accuracy of the physical examination findings. Further research regarding the utility of US for identifying enthesitis at diagnosis of juvenile idiopathic arthritis, accurately predicting disease progression, and guiding therapeutic decisions is warranted. C1 [Weiss, Pamela F.; Chauvin, Nancy A.; Klink, Andrew J.; Feudtner, Chris; Jaramillo, Diego; Sherry, David D.; Keren, Ron] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Localio, Russell] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Colbert, Robert A.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Weiss, PF (reprint author), Childrens Hosp Philadelphia, 3535 Market St,Room 1526, Philadelphia, PA 19104 USA. EM weisspa@email.chop.edu FU NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [1-K23-AR059749-01A1]; Rheumatology Research Foundation; NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases Intramural Research Program) [Z01-AR-041184] FX Dr. Weiss's work was supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant 1-K23-AR059749-01A1); she is also recipient of a Rheumatology Research Foundation Bridge Funding award. 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 34 TC 11 Z9 11 U1 1 U2 2 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 JAN PY 2014 VL 66 IS 1 BP 218 EP 227 DI 10.1002/art.38197 PG 10 WC Rheumatology SC Rheumatology GA AJ0PB UT WOS:000337356300026 PM 24449586 ER PT J AU Steffen-Smith, EA Sarlls, JE Pierpaoli, C Shih, JH Bent, RS Walker, L Warren, KE AF Steffen-Smith, Emilie A. Sarlls, Joelle E. Pierpaoli, Carlo Shih, Joanna H. Bent, Robyn S. Walker, Lindsay Warren, Katherine E. TI Diffusion Tensor Histogram Analysis of Pediatric Diffuse Intrinsic Pontine Glioma SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID APPARENT DIFFUSION; WATER DIFFUSION; MRI; ANISOTROPY; CHILDREN; BRAIN; BEVACIZUMAB; DISTORTION; SURVIVAL; TUMORS AB Purpose. To evaluate tumor structure in children with diffuse intrinsic pontine glioma (DIPG) using histogram analyses of mean diffusivity (MD), determine potential treatment and corticosteroid-related effects on MD, and monitor changes in MD distributions over time. Materials and Methods. DTI was performed on a 1.5T GE scanner. Regions of interest included the entire FLAIR-defined tumor. MD data were used to calculate histograms. Patterns in MD distributions were evaluated and fitted using a two-normal mixture model. Treatment-related effects were evaluated using the R-2 statistic for linear mixed models and Cox proportional hazards models. Results. 12 patients with DIPG underwent one or more DTI exams. MD histogram distributions varied among patients. Over time, histogram peaks became shorter and broader (P = 0.0443). Two-normal mixture fitting revealed large lower curve proportions that were not associated with treatment response or outcome. Corticosteroid use affected MD histograms and was strongly associated with larger, sharper peaks (R-2 = 0.51, P = 0.0028). Conclusions. MD histograms of pediatric DIPG show significant interpatient and intratumoral differences and quantifiable changes in tumor structure over time. Corticosteroids greatly affected MD and must be considered a confounding factor when interpreting MD results in the context of treatment response. C1 [Steffen-Smith, Emilie A.; Bent, Robyn S.; Warren, Katherine E.] NINDS, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Sarlls, Joelle E.] NINDS, Vivo NMR Ctr, NIH, Bethesda, MD 20892 USA. [Pierpaoli, Carlo; Walker, Lindsay] NICHHD, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA. [Shih, Joanna H.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Walker, Lindsay] Brown Univ, Sch Engn, Ctr Biomed Engn, Providence, RI 02912 USA. RP Warren, KE (reprint author), NINDS, Pediat Oncol Branch, NIH, Bldg 10,Room 1-5750,9000 Rockville Pike, Bethesda, MD 20892 USA. EM warrenk@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. The views herein do not necessarily represent the official views of the National Cancer Institute, the National Institutes of Health, or the US Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US Government. Dr. Joanna Shih performed the statistical analysis for this paper. Institutional Review Board approval was obtained. Written informed consent was obtained from all patients or their legal guardians. Results of the clinical trial were previously reported in Warren et al., Cancer 2012. This work was presented in part at the 2012 American Society for Neuroradiology Annual Meeting in New York City, NY. NR 36 TC 4 Z9 4 U1 1 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 647356 DI 10.1155/2014/647356 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AJ6XI UT WOS:000337839400001 ER PT S AU Shirota, H Klinman, DM AF Shirota, Hidekazu Klinman, Dennis M. BE Lawman, MJP Lawman, PD TI TLR-9 Agonist Immunostimulatory Sequence Adjuvants Linked to Cancer Antigens SO CANCER VACCINES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE CpG oligonucleotide; Vaccine; Adjuvant; Tumor ID CPG OLIGODEOXYNUCLEOTIDES; BACTERIAL-DNA; VACCINES; CELLS; ACTIVATION; INDUCTION; IMMUNITY; PROTEIN; MOTIFS AB The primary goal of cancer vaccines is to elicit tumor-specific cytotoxic T lymphocytes (CTL) capable of eradicating established tumors and preventing/eradicating their metastatic spread. CpG oligonucleotides (CpG ODN) activate and support the maturation of immune cells, including plasmacytoid dendritic cells and B lymphocytes, that express Toll-like receptor 9 (TLR9) and are capable of presenting tumor antigens to T cells. Thus, CpG ODN are effective vaccine adjuvants. The adjuvant activity of CpG ODN is improved by maintaining them in close physical and temporal proximity to the co-administered vaccine antigen. This work describes a method of chemically conjugating CpG ODN to antigens and/or cancer cells that improve the resulting CTL response. C1 [Shirota, Hidekazu] Tohoku Univ, Dept Clin Oncol, Sendai, Miyagi 980, Japan. [Klinman, Dennis M.] NCI, Canc & Inflammat Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. RP Shirota, H (reprint author), Tohoku Univ, Dept Clin Oncol, Sendai, Miyagi 980, Japan. FU Intramural NIH HHS NR 15 TC 3 Z9 3 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0345-0; 978-1-4939-0344-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1139 BP 337 EP 344 DI 10.1007/978-1-4939-0345-0_27 D2 10.1007/978-1-4939-0345-0 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology; Immunology SC Biochemistry & Molecular Biology; Oncology; Immunology GA BA2XZ UT WOS:000333984500028 PM 24619691 ER PT S AU Zhang, Y Schreiner, W Rong, YKS AF Zhang, Yi Schreiner, William Rong, Yikang S. BE Storici, F TI Genome Manipulations with Bacterial Recombineering and Site-Specific Integration in Drosophila SO GENE CORRECTION: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Bacterial recombineering; Gene targeting; Drosophila; Site-specific recombination; Genome engineering ID HOMOLOGOUS RECOMBINATION; TARGETED MUTAGENESIS; PROTEIN; HOAP AB Gene targeting is a vital tool for modern biology. The ability to efficiently and repeatedly target the same locus is made more efficient by the site-specific integrase mediated repeated targeting (SIRT) method, which combines homologous recombination, site-specific integration, and bacterial recombineering to conduct targeted modifications of individual loci. Here we describe the recombineering designs and procedures for the introduction of epitope tags, in-frame deletion mutations, and point mutations into plasmids that can later be used for SIRT. C1 [Zhang, Yi; Schreiner, William; Rong, Yikang S.] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Zhang, Y (reprint author), NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 9 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-761-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1114 BP 11 EP 24 DI 10.1007/978-1-62703-761-7_2 D2 10.1007/978-1-62703-761-7 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BA2NU UT WOS:000333711000003 PM 24557894 ER PT S AU Alam, MR Thazhathveetil, AK Li, H Seidman, MM AF Alam, Md. Rowshon Thazhathveetil, Arun Kalliat Li, Hong Seidman, Michael M. BE Storici, F TI Preparation and Application of Triple Helix Forming Oligonucleotides and Single Strand Oligonucleotide Donors for Gene Correction SO GENE CORRECTION: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Triple helix forming oligonucleotide; TFO; Gene targeting; Sequence conversion; Oligonucleotide modification; Oligonucleotide synthesis ID 2'-O-(2-AMINOETHYL) RESIDUES; MAMMALIAN-CELLS; CROSS-LINKING; DNA; PSORALEN; RECOGNITION; MUTAGENESIS; REPAIR; RNA AB Strategies for site-specific modulation of genomic sequences in mammalian cells require two components. One must be capable of recognizing and activating a specific target sequence in vivo, driving that site into an exploitable repair pathway. Information is transferred to the site via participation in the pathway by the second component, a donor nucleic acid, resulting in a permanent change in the target sequence. We have developed biologically active triple helix forming oligonucleotides (TFOs) as site-specific gene targeting reagents. These TFOs, linked to DNA reactive compounds (such as a cross-linking agent), activate pathways that can engage informational donors. We have used the combination of a psoralen-TFO and single strand oligonucleotide donors to generate novel cell lines with directed sequence changes at the target site. Here we describe the synthesis and purification of bioactive psoralen-linked TFOs, their co-introduction into mammalian cells with donor nucleic acids, and the identification of cells with sequence conversion of the target site. We have emphasized details in the synthesis and purification of the oligonucleotides that are essential for preparation of reagents with optimal activity. C1 [Alam, Md. Rowshon] Girindus Amer Inc, Cincinnati, OH 45215 USA. [Thazhathveetil, Arun Kalliat] Northwestern Univ, Dept Chem, Evanston, IL USA. [Li, Hong] LaserGen Inc, Houston, TX USA. [Seidman, Michael M.] NIA, NIH, Baltimore, MD 21224 USA. RP Alam, MR (reprint author), Girindus Amer Inc, Cincinnati, OH 45215 USA. NR 21 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-761-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1114 BP 103 EP 113 DI 10.1007/978-1-62703-761-7_7 D2 10.1007/978-1-62703-761-7 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BA2NU UT WOS:000333711000008 ER PT J AU De Flora, S Izzotti, A D'Agostini, F La Maestra, S Micale, RT Ceccaroli, C Steele, VE Balansky, R AF De Flora, Silvio Izzotti, Alberto D'Agostini, Francesco La Maestra, Sebastiano Micale, Rosanna T. Ceccaroli, Chiara Steele, Vernon E. Balansky, Roumen TI Rationale and Approaches to the Prevention of Smoking-Related Diseases: Overview of Recent Studies on Chemoprevention of Smoking-Induced Tumors in Rodent Models SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE Tobacco smoke; mechanisms; prevention; chemoprevention; molecular end-points ID CIGARETTE-SMOKE; LUNG-CANCER; PHENETHYL ISOTHIOCYANATE; MICRORNA EXPRESSION; PROTEOME PROFILES; N-ACETYLCYSTEINE; TOBACCO-SMOKE; DNA-DAMAGE; MICE; AGENTS AB Tobacco smoke plays a dominant role in the epidemiology of lung cancer, cancer at other sites, and a variety of other chronic diseases. It is the leading cause of death in developed countries, and the global burden of cancer is escalating in less developed regions. For a rational implementation of strategies exploitable for the prevention smoking-related diseases, it is crucial to elucidate both the mechanisms of action of cigarette smoke and the protective mechanisms of the host organism. The imperative primary prevention goal is to avoid any type of exposure to smoke. Epidemiological studies have shown that a decrease in the consumption of cigarettes can be successful in attenuating the epidemic of lung cancer in several countries. Chemoprevention by means of dietary and/or pharmacological agents provides a complementary strategy aimed at decreasing the risk of developing smoking-associated diseases in addicted current smokers, who are unable to quit smoking, and especially in involuntary smokers and ex-smokers. The availability of new animal models that are suitable to detect the carcinogenicity of cigarette smoke and to assess the underlying molecular mechanisms provides new tools for evaluating both safety and efficacy of putative chemopreventive agents. C1 [De Flora, Silvio; Izzotti, Alberto; D'Agostini, Francesco; La Maestra, Sebastiano; Micale, Rosanna T.; Ceccaroli, Chiara] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. [Izzotti, Alberto] IRCCS Azienda Osped Univ San Martino, IST Natl Inst Canc Res, Mutagenesis Unit, Genoa, Italy. [Steele, Vernon E.] NCI, Rockville, MD USA. [Balansky, Roumen] Natl Oncol Ctr, BU-1157 Sofia, Bulgaria. RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy. EM sdf@unige.it OI izzotti, alberto/0000-0002-8588-0347 FU U.S. National Cancer Institute; Bulgarian Ministry of Education, Youth and Science (National Science Foundation) FX The chemoprevention studies cited in this article were supported by the U.S. National Cancer Institute and by the Bulgarian Ministry of Education, Youth and Science (National Science Foundation). NR 41 TC 5 Z9 5 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1059-0501 EI 1532-4095 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2014 VL 32 IS 2 BP 105 EP 120 DI 10.1080/10590501.2014.907459 PG 16 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA AJ4AB UT WOS:000337610000001 PM 24875440 ER PT S AU Farag, A Liu, JM Summers, RM AF Farag, Amal Liu, Jiamin Summers, Ronald M. BE MelloThoms, CR Kupinski, MA TI Automatic Segmentation of Abdominal Vessels for Improved Pancreas Localization SO MEDICAL IMAGING 2014: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Perception, Observer Performance, and Technology Assessment CY FEB 16-17, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med DE Abdominal Vessel Segmentation; vessel tracking; statistical-modeling of vessels AB Accurate automatic detection and segmentation of abdominal organs from CT images is important for quantitative and qualitative organ tissue analysis as well as computer-aided diagnosis. The large variability of organ locations, the spatial interaction between organs that appear similar in medical scans and orientation and size variations are among the major challenges making the task very difficult. The pancreas poses these challenges in addition to its flexibility which allows for the shape of the tissue to vastly change. Due to the close proximity of the pancreas to numerous surrounding organs within the abdominal cavity the organ shifts according to the conditions of the organs within the abdomen, as such the pancreas is constantly changing. Combining these challenges with typically found patient-to-patient variations and scanning conditions the pancreas becomes harder to localize. In this paper we focus on three abdominal vessels that almost always abut the pancreas tissue and as such useful landmarks to identify the relative location of the pancreas. The splenic and portal veins extend from the hila of the spleen and liver, respectively, travel through the abdominal cavity and join at a position close to the head of the pancreas known as the portal confluence. A third vein, the superior mesenteric vein, anastomoses with the other two veins at the portal confluence. An automatic segmentation framework for obtaining the splenic vein, portal confluence and superior mesenteric vein is proposed using 17 contrast enhanced computed-tomography datasets. The proposed method uses outputs from the multi-organ multi-atlas label fusion and Frangi vesselness filter to obtain automatic seed points for vessel tracking and generation of statistical models of the desired vessels. The approach shows ability to identify the vessels and improve localization of the pancreas within the abdomen. C1 [Farag, Amal; Liu, Jiamin; Summers, Ronald M.] NIH, Imaging Biomarkers & CAD Lab, Dept Radiol & Imaging Sci, Hlth Clin Ctr, Bethesda, MD 20892 USA. RP Farag, A (reprint author), NIH, Imaging Biomarkers & CAD Lab, Dept Radiol & Imaging Sci, Hlth Clin Ctr, Bldg 10 Room 1C224D MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov NR 12 TC 1 Z9 1 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9830-4 J9 PROC SPIE PY 2014 VL 9037 AR 90371M DI 10.1117/12.2043867 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7IZ UT WOS:000337585600053 ER PT S AU Gallas, BD Cheng, WC Gavrielides, MA Ivansky, A Keay, T Wunderlich, A Hipp, J Hewitt, SM AF Gallas, Brandon D. Cheng, Wei-Chung Gavrielides, Marios A. Ivansky, Adam Keay, Tyler Wunderlich, Adam Hipp, Jason Hewitt, Stephen M. BE MelloThoms, CR Kupinski, MA TI eeDAP: An Evaluation Environment for Digital and Analog Pathology SO MEDICAL IMAGING 2014: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Perception, Observer Performance, and Technology Assessment CY FEB 16-17, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med DE Digital Pathology; Whole Slide Imaging; Reader Studies; Technology Evaluation AB Purpose: The purpose of this work is to present a platform for designing and executing studies that compare pathologists interpreting histopathology of whole slide images (WSI) on a computer display to pathologists interpreting glass slides on an optical microscope. Methods: Here we present eeDAP, an evaluation environment for digital and analog pathology. The key element in eeDAP is the registration of the WSI to the glass slide. Registration is accomplished through computer control of the microscope stage and a camera mounted on the microscope that acquires images of the real time microscope view. Registration allows for the evaluation of the same regions of interest (ROIs) in both domains. This can reduce or eliminate disagreements that arise from pathologists interpreting different areas and focuses the comparison on image quality. Results: We reduced the pathologist interpretation area from an entire glass slide (approximate to 10-30 mm)(2) to small ROIs < (50 um)(2). We also made possible the evaluation of individual cells. Conclusions: We summarize eeDAP's software and hardware and provide calculations and corresponding images of the microscope field of view and the ROIs extracted from the WSIs. These calculations help provide a sense of eeDAP's functionality and operating principles, while the images provide a sense of the look and feel of studies that can be conducted in the digital and analog domains. The eeDAP software can be downloaded from code. google.com (project: eeDAP) as Matlab source or as a precompiled stand-alone license-free application. C1 [Gallas, Brandon D.; Cheng, Wei-Chung; Gavrielides, Marios A.; Ivansky, Adam; Keay, Tyler; Wunderlich, Adam] US FDA, Div Imaging & Appl Math, OSEL, CDRH, Silver Spring, MD 20993 USA. [Hipp, Jason; Hewitt, Stephen M.] Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Pathol Lab, Bethesda, MD USA. RP Gallas, BD (reprint author), US FDA, Div Imaging & Appl Math, OSEL, CDRH, Silver Spring, MD 20993 USA. EM brandon.gallas@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620; Hewitt, Stephen/0000-0001-8283-1788 FU U. S. Food and Drug Administration (FDA/ CDRH) FX This research project was partially funded through a Critical Path grant from the U. S. Food and Drug Administration (FDA/ CDRH). We would like to acknowledge Catherine Conway, formerly at the NIH, for her active involvement in the project, including the preparation and annotation of slides and training materials.; . NR 9 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9830-4 J9 PROC SPIE PY 2014 VL 9037 AR UNSP 903709 DI 10.1117/12.2044443 PG 12 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7IZ UT WOS:000337585600008 ER PT S AU Rahman, MM Antani, SK Demner-Fushman, D Thoma, GR AF Rahman, Md Mahmudur Antani, Sameer K. Demner-Fushman, Dina Thoma, George R. BE Law, MY Cook, TS TI Biomedical Image Representation and Classification Using an Entropy Weighted Probabilistic Concept Feature Space SO MEDICAL IMAGING 2014: PACS AND IMAGING INFORMATICS: NEXT GENERATION AND INNOVATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - PACS and Imaging Informatics - Next Generation and Innovations CY FEB 18-20, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med ID RETRIEVAL AB This paper presents a novel approach to biomedical image representation for classification by mapping image regions to local concepts and represent images in a weighted entropy based probabilistic feature space. In a heterogeneous collection of medical images, it is possible to identify specific local patches that are perceptually and/or semantically distinguishable. The variation of these patches is effectively modeled as local concepts based on their low-level features as inputs to a multi-class SVM classifier. The probability of occurrence of each concept in an image is measured by spreading and normalizing each region's class confidence score based on the probabilistic output of the classifier. Furthermore, importance of concepts is measured as Shannon entropy based on pixel values of image patches and used to refine the feature vector to overcome the limitation of the "TF-IDF"-based weighting. In addition, to take the localization information of concepts into consideration, each image each segmented into five overlapping regions and local concept feature vectors are generated from those regions to finally obtain a combined semi-global feature vector. A systematic evaluation of image classification on two biomedical image data sets demonstrates improvement of more than 10% for the proposed feature representation approach compared to the commonly used low level and visual word-based approaches. C1 [Rahman, Md Mahmudur; Antani, Sameer K.; Demner-Fushman, Dina; Thoma, George R.] NIH, US Natl Lib Med, Bethesda, MD 20892 USA. RP Rahman, MM (reprint author), NIH, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM rahmanmm@mail.nih.gov OI Antani, Sameer/0000-0002-0040-1387 NR 13 TC 1 Z9 1 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9832-8 J9 PROC SPIE PY 2014 VL 9039 AR 903908 DI 10.1117/12.2043911 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7IY UT WOS:000337584000006 ER PT S AU Xue, ZY You, D Antani, S Long, LR Demner-Fushman, D Thoma, GR AF Xue, Zhiyun You, Daekeun Antani, Sameer Long, L. Rodney Demner-Fushman, Dina Thoma, George R. BE Law, MY Cook, TS TI Classification of Visual Signs in Abdominal CT Image Figures in Biomedical Literature SO MEDICAL IMAGING 2014: PACS AND IMAGING INFORMATICS: NEXT GENERATION AND INNOVATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - PACS and Imaging Informatics - Next Generation and Innovations CY FEB 18-20, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med DE image classification; abdominal CT imaging signs; content-based image retrieval; visual ontology ID RETRIEVAL; FEATURES; SEARCH; ENGINE AB "Imaging signs" are a critical part of radiology's language. They not only are important for conveying diagnosis, but may also aid in indexing radiology literature and retrieving relevant cases and images. Here we report our work towards representing and categorizing imaging signs of abdominal abnormalities in figures in the radiology literature. Given a region-of-interest (ROI) from a figure, our goal was to assign a correct imaging sign label to that ROI from the following seven: accordion, comb, ring, sandwich, small bowel feces, target, or whirl. As training and test data, we created our own "gold standard" dataset of regions containing imaging signs. We computed 2997 feature attributes to represent imaging sign characteristics for each ROI in training and test sets. Following feature selection they were reduced to 70 attributes and were input to a Support Vector Machine classifier. We applied image-enhancement methods to compensate for variable quality of the images in radiology articles. In particular we developed a method for automatic detection and removal of pointers/markers (arrows, arrowheads, and asterisk symbols) on the images. These pointers/markers are valuable for approximately locating ROIs; however, they degrade the classification because they are often (partially) included in the training ROIs. On a test set of 283 ROIs, our method achieved an overall accuracy of 70% in labeling the seven signs, which we believe is a promising result for using imaging signs to search/retrieve radiology literature. This work is also potentially valuable for the creation of a visual ontology of biomedical imaging entities. C1 [Xue, Zhiyun; You, Daekeun; Antani, Sameer; Long, L. Rodney; Demner-Fushman, Dina; Thoma, George R.] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Xue, ZY (reprint author), NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 34 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9832-8 J9 PROC SPIE PY 2014 VL 9039 AR 90390L DI 10.1117/12.2043045 PG 10 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7IY UT WOS:000337584000018 ER PT S AU Padalkar, M McGoverin, C Onigbanjo, Q Spencer, R Barbash, S Kropf, E Pleshko, N AF Padalkar, Mugdha McGoverin, Cushla Onigbanjo, Quam Spencer, Richard Barbash, Scott Kropf, Eric Pleshko, Nancy BE Choi, B Kollias, N Zeng, H Kang, HW Wong, BJF Ilgner, JF Tearney, GJ Gregory, KW Marcu, L Mandelis, A TI Infrared Fiber Optic Probes for Evaluation of Musculoskeletal Tissue Pathology SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics X CY FEB 01-02, 2014 CL San Francisco, CA SP SPIE DE Anterior cruciate ligament; tendon; cartilage; infrared fiber optic probes; mid infrared spectroscopy; near infrared spectroscopy; partial least squares discriminant analysis; linear discriminant analysis ID ANTERIOR CRUCIATE LIGAMENT; BOVINE ARTICULAR-CARTILAGE; NIR SPECTROSCOPY; OSTEOARTHRITIS; RECONSTRUCTION; COMPRESSION; GRAFT; MRI AB Musculoskeletal pathology of the knee commonly occurs with aging and as a result of injury. The incidence of anterior cruciate ligament (ACL) injuries continues to increase annually, and may precede the eventual onset of osteoarthritis (OA), a debilitating and prevalent disease characterized by cartilage degeneration. Early detection of OA remains elusive, with current imaging methods lacking adequate sensitivity to detect early pathologic cartilage changes. We used mid- and near-infrared (IR) spectroscopy through arthroscopic-based fiber-optic devices to assess cartilage damage and differentiate tendon from ligament. Mid-IR spectroscopy is characterized by distinct bands and low penetration depth (<10 mu m) and near-IR spectroscopy is characterized by complex overlapping bands and greater penetration depths (<1 cm). We have found that combined mid-and near-IR analysis greatly extends the information available through either in the analysis of soft tissues, including cartilage, ligaments and tendons. We discuss here basic science studies and the potential for translation to clinical research with novel arthroscopic probes. C1 [Padalkar, Mugdha; McGoverin, Cushla; Onigbanjo, Quam; Pleshko, Nancy] Temple Univ, Dept Bioengn, Philadelphia, PA 19122 USA. [Spencer, Richard] Natl Inst Aging, Natl Inst Hlth, Baltimore, MD 21224 USA. [Barbash, Scott; Kropf, Eric] Temple Univ, Sch Med, Dept Orthopaed Surg & Sports Med, Philadelphia, PA 19122 USA. RP Padalkar, M (reprint author), Temple Univ, Dept Bioengn, Philadelphia, PA 19122 USA. FU NIH [EB000744, AR056145] FX This study was supported in part by the NIH Intramural Program, and by NIH EB000744 and AR056145. NR 39 TC 0 Z9 0 U1 2 U2 6 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9839-7 J9 PROC SPIE PY 2014 VL 8926 AR UNSP 89263Y DI 10.1117/12.2047473 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BA7IP UT WOS:000337574500065 ER PT S AU Schlom, J Hodge, JW Palena, C Tsang, KY Jochems, C Greiner, JW Farsaci, B Madan, RA Heery, CR Gulley, JL AF Schlom, Jeffrey Hodge, James W. Palena, Claudia Tsang, Kwong-Yok Jochems, Caroline Greiner, John W. Farsaci, Benedetto Madan, Ravi A. Heery, Christopher R. Gulley, James L. BE Tew, KD Fisher, PB TI Therapeutic Cancer Vaccines SO ADVANCES IN CANCER RESEARCH, VOL 121 SE Advances in Cancer Research LA English DT Review; Book Chapter ID RESISTANT PROSTATE-CANCER; COLONY-STIMULATING FACTOR; T-CELL RESPONSES; LONG-TERM SURVIVAL; METASTATIC COLORECTAL-CANCER; EPITHELIAL-MESENCHYMAL TRANSITIONS; CARCINOEMBRYONIC ANTIGEN CEA; CHRONIC VIRAL-INFECTION; DOSE-ESCALATION TRIAL; RANDOMIZED PHASE-II AB Therapeutic cancer vaccines have the potential of being integrated in the therapy of numerous cancer types and stages. The wide spectrum of vaccine platforms and vaccine targets is reviewed along with the potential for development of vaccines to target cancer cell "stemness," the epithelial-to-mesenchymal transition (EMT) phenotype, and drug-resistant populations. Preclinical and recent clinical studies are now revealing how vaccines can optimally be used with other immune-based therapies such as checkpoint inhibitors, and so-called nonimmune-based therapeutics, radiation, hormonal therapy, and certain small molecule targeted therapies; it is now being revealed that many of these traditional therapies can lyse tumor cells in a manner as to further potentiate the host immune response, alter the phenotype of nonlysed tumor cells to render them more susceptible to T-cell lysis, and/or shift the balance of effector:regulatory cells in a manner to enhance vaccine efficacy. The importance of the tumor microenvironment, the appropriate patient population, and clinical trial endpoints is also discussed in the context of optimizing patient benefit from vaccine-mediated therapy. C1 [Schlom, Jeffrey; Hodge, James W.; Palena, Claudia; Tsang, Kwong-Yok; Jochems, Caroline; Greiner, John W.; Farsaci, Benedetto; Madan, Ravi A.; Heery, Christopher R.; Gulley, James L.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM js141c@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 NR 197 TC 13 Z9 13 U1 1 U2 12 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X BN 978-0-12-800249-0 J9 ADV CANCER RES JI Adv.Cancer Res. PY 2014 VL 121 BP 67 EP 124 DI 10.1016/B978-0-12-800249-0.00002-0 PG 58 WC Oncology SC Oncology GA BA7DU UT WOS:000337494000002 PM 24889529 ER PT J AU Levine, KE Han, L Gwinn, WM Morgan, DL Ross, GT Essader, AS Fernando, RA Haines, LG Robinson, VG AF Levine, Keith E. Han, Li Gwinn, William M. Morgan, Daniel L. Ross, Glenn T. Essader, Amal S. Fernando, Reshan A. Haines, Laura G. Robinson, Veronica G. TI DEVELOPMENT AND OPTIMIZATION OF A PROCEDURE FOR THE DETERMINATION OF INDIUM-TIN OXIDE PARTICLE SIZE AND CONCENTRATION IN CELLULAR MEDIA SO ANALYTICAL LETTERS LA English DT Article DE Dynamic light scattering; Indium-tin oxide; Inductively coupled plasma mass spectrometry; Physicochemical characterization ID PULMONARY TOXICITY; INTRATRACHEAL INSTILLATIONS; SINTERING BEHAVIOR; INHALATION; WORKERS; HAMSTERS; LUNGS; MICE AB Indium-tin oxide (ITO) is a solid mixture often comprised of approximately 90% indium oxide and 10% tin oxide by weight. ITO is employed as a transparent conductive coating for flat panel, liquid crystal, and plasma displays and is typically deposited after sintering as a thin film on a substrate through a variety of processes. Unfortunately, there have been published reports of workers who have been adversely impacted through exposure to this compound. When these reports are coupled with the industrial utility of ITO, future toxicological investigations are likely. Comprehensive characterization of ITO test materials would be an essential component of these studies. Ideally, characterization would include assessment of ITO particle size as administered during dosing because this physicochemical parameter can significantly impact solubility. The objective of this task was to develop, optimize, and apply a dynamic light scattering (DLS) sample preparation and measurement protocol for determination of particle size for a suite of sintered/non-sintered ITO samples prepared in cellular growth media at nominal 0.3 mg/mL doses. Sonication time was evaluated from 15 to 90 minutes over a 24-hour, continuous DLS measurement period. Resulting suspensions from samples subjected to 30 minute sonication times were stable with respect to hydrodynamic particle size between 10 and 24 hours after sonication. Throughout the 24-hour DLS measurement period, suspension aliquots were analyzed by inductively coupled plasma mass spectrometry to determine indium concentration. The developed protocol enabled investigators to use ITO suspensions of known hydrodynamic particle size and concentration in their in vitro cellular study. C1 [Levine, Keith E.; Han, Li; Ross, Glenn T.; Essader, Amal S.; Fernando, Reshan A.; Haines, Laura G.] RTI Int, Res Triangle Pk, NC 27709 USA. [Gwinn, William M.; Morgan, Daniel L.; Robinson, Veronica G.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Levine, KE (reprint author), RTI Int, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA. EM levine@rti.org FU National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services [HHSN273201100003C] FX This work was performed for The Division of National Toxicology program, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, under contract No. HHSN273201100003C. This article may be the work product of an employee or group of employees of the National Institute of Environmental Health Sciences (NIEHS), National Institute of Health (NIH); however, the statements, opinions, or conclusions contained therein do not necessarily represent the statements, opinions, or conclusions of NIEHS, NIH, or the United States government. NR 30 TC 1 Z9 1 U1 2 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0003-2719 EI 1532-236X J9 ANAL LETT JI Anal. Lett. PY 2014 VL 47 IS 9 BP 1614 EP 1625 DI 10.1080/00032719.2013.878841 PG 12 WC Chemistry, Analytical SC Chemistry GA AJ0PN UT WOS:000337357600015 ER PT J AU Susarla, BTS Villapol, S Yi, JH Geller, HM Symes, AJ AF Susarla, Bala T. S. Villapol, Sonia Yi, Jae-Hyuk Geller, Herbert M. Symes, Aviva J. TI Temporal patterns of cortical proliferation of glial cell populations after traumatic brain injury in mice SO ASN NEURO LA English DT Article DE astrocytes; BrdU; microglia; neurogenesis; NG2; proliferation; traumatic brain injury (TBI) ID CENTRAL-NERVOUS-SYSTEM; ADULT-RAT; ENHANCED NEUROGENESIS; SUBVENTRICULAR ZONE; EXPRESSING CELLS; IMPACT INJURY; SPINAL-CORD; SCAR; ASTROCYTES; MICROGLIA AB TBI (traumatic brain injury) triggers an inflammatory cascade, gliosis and cell proliferation following cell death in the pericontusional area and surrounding the site of injury. In order to better understand the proliferative response following CCI (controlled cortical impact) injury, we systematically analyzed the phenotype of dividing cells at several time points post-lesion. C57BL/6 mice were subjected to mild to moderate CCI over the left sensory motor cortex. At different time points following injury, mice were injected with BrdU (bromodeoxyuridine) four times at 3-h intervals and then killed. The greatest number of proliferating cells in the pericontusional region was detected at 3 dpi (days post-injury). At 1 dpi, NG2(+) cells were the most proliferative population, and at 3 and 7 dpi the Iba-1(+) microglial cells were proliferating more. A smaller, but significant number of GFAP(+) (glial fibrillary acidic protein) astrocytes proliferated at all three time points. Interestingly, at 3 dpi we found a small number of proliferating neuroblasts [DCX+ (doublecortin)] in the injured cortex. To determine the cell fate of proliferative cells, mice were injected four times with BrdU at 3 dpi and killed at 28 dpi. Approximately 70% of proliferative cells observed at 28 dpi were GFAP+ astrocytes. In conclusion, our data suggest that the specific glial cell types respond differentially to injury, suggesting that each cell type responds to a specific pattern of growth factor stimulation at each time point after injury. C1 [Susarla, Bala T. S.; Villapol, Sonia; Yi, Jae-Hyuk; Symes, Aviva J.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Susarla, Bala T. S.; Villapol, Sonia; Symes, Aviva J.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. [Yi, Jae-Hyuk; Geller, Herbert M.] NHLBI, Dev Neurobiol Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Symes, AJ (reprint author), Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. EM aviva.symes@usuhs.edu RI Symes, Aviva/S-7471-2016; OI Symes, Aviva/0000-0003-2557-9939; Geller, Herbert/0000-0002-7048-6144 FU Center for Neuroscience and Regenerative Medicine [300604-11.0-60855] FX This work was funded by a grant from the Center for Neuroscience and Regenerative Medicine [grant number 300604-11.0-60855]. NR 59 TC 15 Z9 15 U1 1 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1759-0914 J9 ASN NEURO JI ASN Neuro PY 2014 VL 6 IS 3 AR e00143 DI 10.1042/AN20130034 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AJ2BT UT WOS:000337460700003 PM 24670035 ER PT J AU Susarla, BTS Villapol, S Yi, JH Geller, HM Symes, AJ AF Susarla, Bala T. S. Villapol, Sonia Yi, Jae-Hyuk Geller, Herbert M. Symes, Aviva J. TI Temporal patterns of cortical proliferation of glial cell populations after traumatic brain injury in mice SO ASN NEURO LA English DT Editorial Material C1 [Susarla, Bala T. S.; Villapol, Sonia; Yi, Jae-Hyuk; Symes, Aviva J.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Susarla, Bala T. S.; Villapol, Sonia; Symes, Aviva J.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. [Yi, Jae-Hyuk; Geller, Herbert M.] NHLBI, Dev Neurobiol Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Symes, AJ (reprint author), Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. EM aviva.symes@usuhs.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1759-0914 J9 ASN NEURO JI ASN Neuro PY 2014 VL 6 IS 3 PG 1 WC Neurosciences SC Neurosciences & Neurology GA AJ2BT UT WOS:000337460700004 ER PT J AU Gotts, SJ Martin, A AF Gotts, Stephen J. Martin, Alex TI The nature and role of cortical feedback in perception, imagery, and synesthesia SO COGNITIVE NEUROSCIENCE LA English DT Article AB In his Discussion Paper, Seth makes the case for counterfactual richness of predictive processing models in explaining perceptual presence and its absence in synesthetic concurrent percepts. Here, we question the relevance of counterfactual richness for these and related phenomena, and we argue that alternative theories of perception that incorporate top-down/bottom-up facilitatory interactions are at no relative disadvantage in addressing them. C1 [Gotts, Stephen J.; Martin, Alex] NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Gotts, SJ (reprint author), NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. EM gottss@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 7 TC 1 Z9 1 U1 0 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1758-8928 EI 1758-8936 J9 COGN NEUROSCI-UK JI Cogn. Neurosci PY 2014 VL 5 IS 2 BP 121 EP 122 DI 10.1080/17588928.2014.905518 PG 4 WC Neurosciences SC Neurosciences & Neurology GA AI9GZ UT WOS:000337242400006 PM 24702431 ER PT J AU Jaworska, A Tannenbaum, J AF Jaworska, Agnieszka Tannenbaum, Julie TI Person-Rearing Relationships as a Key to Higher Moral Status SO ETHICS LA English DT Article AB Why does a baby who is otherwise cognitively similar to an animal such as a dog nevertheless have a higher moral status? We explain the difference in moral status as follows: the baby can, while a dog cannot, participate as a rearee in what we call "person-rearing relationships," which can transform metaphysically and evaluatively the baby's activities. The capacity to engage in these transformed activities has the same type of value as the very capacities (i.e., intellectual or emotional sophistication) that explain unimpaired adult humans' high moral status. We attempt to extend this account to individuals with severe cognitive impairments. C1 [Jaworska, Agnieszka] Univ Calif Riverside, Riverside, CA 92521 USA. [Jaworska, Agnieszka] Stanford Univ, Stanford, CA 94305 USA. [Jaworska, Agnieszka; Tannenbaum, Julie] NIH, Dept Bioeth, Bethesda, MD USA. [Tannenbaum, Julie] Pomona Coll, Claremont, CA 91711 USA. RP Jaworska, A (reprint author), Univ Calif Riverside, Riverside, CA 92521 USA. EM jaworska@ucr.edu; julie.tannenbaum@pomona.edu NR 14 TC 5 Z9 5 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0014-1704 EI 1539-297X J9 ETHICS JI Ethics PD JAN PY 2014 VL 124 IS 2 BP 242 EP 271 DI 10.1086/673431 PG 30 WC Ethics; Philosophy SC Social Sciences - Other Topics; Philosophy GA AI9BM UT WOS:000337221500002 ER PT S AU Kwak, JT Xu, S Pinto, PA Turkbey, B Bernardo, M Choyke, PL Wood, BJ AF Kwak, Jin Tae Xu, Sheng Pinto, Peter A. Turkbey, Baris Bernardo, Marcelino Choyke, Peter L. Wood, Bradford J. BE Gurcan, MN Madabhushi, A TI A multiview boosting approach to tissue segmentation SO MEDICAL IMAGING 2014: DIGITAL PATHOLOGY SE Proceedings of SPIE LA English DT Proceedings Paper CT 2nd Conference on Medical Imaging - Digital Pathology CY FEB 16-17, 2014 CL San Diego, CA SP SPIE, Modus Med Devices Inc, XIFIN Inc, Ventana Med Syst Inc, Intrace Med DE tissue segmentation; multiview boosting; digital pathology; prostate cancer ID IMAGES; PROSTATE; CLASSIFICATION AB Digitized histopathology images have a great potential for improving or facilitating current assessment tools in cancer pathology. In order to develop accurate and robust automated methods, the precise segmentation of histologic objects such epithelium, stroma, and nucleus is necessary, in the hopes of information extraction not otherwise obvious to the subjective eye. Here, we propose a multivew boosting approach to segment histology objects of prostate tissue. Tissue specimen images are first represented at different scales using a Gaussian kernel and converted into several forms such HSV and La*b*. Intensity- and texture-based features are extracted from the converted images. Adopting multiview boosting approach, we effectively learn a classifier to predict the histologic class of a pixel in a prostate tissue specimen. The method attempts to integrate the information from multiple scales (or views). 18 prostate tissue specimens from 4 patients were employed to evaluate the new method. The method was trained on 11 tissue specimens including 75,832 epithelial and 103,453 stroma pixels and tested on 55,319 epithelial and 74,945 stroma pixels from 7 tissue specimens. The technique showed 96.7% accuracy, and as summarized into a receiver operating characteristic (ROC) plot, the area under the ROC curve (AUC) of 0.983 (95% CI: 0.983-0.984) was achieved. C1 [Kwak, Jin Tae; Xu, Sheng; Wood, Bradford J.] Natl Inst Hlth Clin Ctr, Ctr Intervent Oncol, Bethesda, MD 20892 USA. [Pinto, Peter A.] Natl Canc Inst, Natl Inst Hlth, Mol Imaging Program, Bethesda, MD 20892 USA. [Turkbey, Baris; Bernardo, Marcelino; Choyke, Peter L.] Natl Canc Inst, Natl Inst Hlth, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Kwak, JT (reprint author), Natl Inst Hlth Clin Ctr, Ctr Intervent Oncol, Bethesda, MD 20892 USA. EM jintae.kwak@nih.gov NR 22 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9834-2 J9 PROC SPIE PY 2014 VL 9041 AR UNSP 90410R DI 10.1117/12.2043966 PG 7 WC Optics; Pathology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Pathology; Radiology, Nuclear Medicine & Medical Imaging GA BA6VF UT WOS:000337288300022 ER PT J AU Murase, SK Haspel, N del Valle, LJ Perpete, EA Michaux, C Nussinov, R Puiggali, J Aleman, C AF Murase, Sara K. Haspel, Nurit del Valle, Luis J. Perpete, Eric A. Michaux, Catherine Nussinov, Ruth Puiggali, Jordi Aleman, Carlos TI Molecular characterization of L-phenylalanine terminated poly(L-lactide) conjugates SO RSC ADVANCES LA English DT Article ID AROMATIC INTERACTIONS; DYNAMICS SIMULATIONS; BLOCK-COPOLYMERS; FORCE-FIELD; PEPTIDE; POLYMER; PROTEINS; CONFORMATION; MORPHOLOGY; DESIGN AB Peptide-polymer conjugates made of poly(L-lactide) and L-phenylalanine or L, L-diphenylalanine (F-PLA and FF-PLA, respectively) have been synthesized by the ring-opening polymerization of L-lactide using the peptide fragment as an initiator. The structure of the conjugates was confirmed by H-1 NMR, FT-IR, GPC, UV-Vis and CD. Molecular dynamics simulations have been used to identify both the conformational preferences of the FF-PLA conjugate in solution and the potential intramolecular interactions between the peptide and polymer blocks, while TD-DFT calculations have been applied to model the electronic transitions observed by the UV-Vis absorption spectroscopy. Results show that the polymer fragment prefers a random coil or a mix of helix/strand while the peptide fragment tends to have folded and helical conformations. Although the degree of interaction between the two fragments is slightly higher than that reported for other peptide-polymer conjugates, it is small enough to suggest that FF-PLA is a potential candidate to aggregate forming peptide-guided organizations via self-assembly. On the other hand, quantum mechanical calculations have allowed us to identify the pi -> pi* transition, which is typically observed in helical peptides and proteins, as well as the n -> pi* transition along the N-C-O backbone. C1 [Murase, Sara K.; del Valle, Luis J.; Puiggali, Jordi; Aleman, Carlos] Univ Politecn Cataluna, ETSEIB, Dept Chem Engn, E-08028 Barcelona, Spain. [Haspel, Nurit] Univ Massachusetts, Dept Comp Sci, Boston, MA 02125 USA. [Perpete, Eric A.; Michaux, Catherine] Univ Namur, Unit Chim Phys Theor & Struct, B-5000 Namur, Belgium. [Nussinov, Ruth] NCI, Leidos Biomed Res Inc, Canc & Inflammat Program, Basic Sci Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. [Puiggali, Jordi; Aleman, Carlos] Univ Politecn Cataluna, Ctr Res Nanoengn, E-08028 Barcelona, Spain. RP Puiggali, J (reprint author), Univ Politecn Cataluna, ETSEIB, Dept Chem Engn, Av Diagonal 647, E-08028 Barcelona, Spain. EM nurit.haspel@umb.edu; eric.perpete@unamur.be; jordi.puiggali@upc.edu; carlos.aleman@upc.edu RI del Valle, Luis J./I-1342-2015; Haspel, Nurit/D-1961-2017; OI del Valle, Luis J./0000-0001-9916-1741; Puiggali, Jordi/0000-0002-0640-4474 FU BMICINN-FEDER funds [MAT2012-34498, MAT2012-36205]; Generalitat de Catalunya [2009SGR925, 2009SGR1208, XRQTC]; ICREA Academia; Belgian National Fund for Scientific Research (F.R.S.-FNRS) FX This work was supported by BMICINN-FEDER funds (MAT2012-34498 and MAT2012-36205), and by the Generalitat de Catalunya (2009SGR925, 2009SGR1208 and XRQTC). Authors are indebted to the Centre de Supercomputacio de Catalunya (CESCA) for computational facilities. Support for the research of C.A. was received through the "ICREA Academia". We thank Dr Guillermo Revilla-Lopez for his help with the computational simulations. The calculations were carried out in part on the supercomputing facilities in the College of Science and Mathematics at UMass Boston. This research used resources of the "Plateforme Technologique de Calcul Intensif (PTCI)" located at the University of Namur, Belgium, which is supported by the Belgian National Fund for Scientific Research (F.R.S.-FNRS). Catherine Michaux and Eric A. Perpete also thank the Belgian National Fund for Scientific Research for their associate and senior research associate positions, respectively. NR 60 TC 5 Z9 5 U1 3 U2 25 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2046-2069 J9 RSC ADV JI RSC Adv. PY 2014 VL 4 IS 44 BP 23231 EP 23241 DI 10.1039/c4ra01534g PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA AI8FQ UT WOS:000337145200055 ER PT J AU Phillips, KA Jobes, ML Epstein, DH Preston, KL AF Phillips, Karran A. Jobes, Michelle L. Epstein, David H. Preston, Kenzie L. TI Evaluation of Drinking and Drug Use Utilizing Ecological Momentary Assessment SO SUBSTANCE ABUSE LA English DT Meeting Abstract C1 [Phillips, Karran A.] NIDA, IRP, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PY 2014 VL 35 IS 2 BP 204 EP 204 PG 1 WC Substance Abuse SC Substance Abuse GA AI9HY UT WOS:000337244900048 ER PT J AU Charoenpanich, A Wall, ME Tucker, CJ Andrews, DMK Lalush, DS Dirschl, DR Loboa, EG AF Charoenpanich, Adisri Wall, Michelle E. Tucker, Charles J. Andrews, Danica M. K. Lalush, David S. Dirschl, Douglas R. Loboa, Elizabeth G. TI Cyclic Tensile Strain Enhances Osteogenesis and Angiogenesis in Mesenchymal Stem Cells from Osteoporotic Donors SO TISSUE ENGINEERING PART A LA English DT Article ID HUMAN BONE-MARROW; MANDIBULAR DISTRACTION OSTEOGENESIS; MECHANICAL STRAIN; OSTEOBLAST DIFFERENTIATION; STROMAL CELLS; MORPHOGENIC PROTEIN; SIGNALING PATHWAYS; MINERAL DENSITY; TRABECULAR BONE; SELF-RENEWAL AB We have shown that the uniaxial cyclic tensile strain of magnitude 10% promotes and enhances osteogenesis of human mesenchymal stem cells (hMSC) and human adipose-derived stem cells (hASC) from normal, nonosteoporotic donors. In the present study, MSC from osteoporotic donors were analyzed for changes in mRNA expression in response to 10% uniaxial tensile strain to identify potential mechanisms underlying the use of this mechanical loading paradigm for prevention and treatment of osteoporosis. Human MSC isolated from three female, postmenopausal osteoporotic donors were analyzed for their responses to mechanical loading using microarray analysis of over 47,000 gene probes. Human MSC were seeded in three-dimensional collagen type I constructs to mimic the organic extracellular matrix of bone and 10% uniaxial cyclic tensile strain was applied to promote osteogenesis. Seventy-nine genes were shown to be regulated within hMSC from osteoporotic donors in response to 10% cyclic tensile strain. Upregulation of six genes were further confirmed with realtime RT-PCR: jun D proto-oncogene (JUND) and plasminogen activator, urokinase receptor (PLAUR), two genes identified as potential key molecules from network analysis; phosphoinositide-3-kinase, catalytic, delta polypeptide (PIK3CD) and wingless-type MMTV integration site family, member 5B (WNT5B), two genes with known importance in bone biology; and, PDZ and LIM domain 4 (PDLIM4) and vascular endothelial growth factor A (VEGFA), two genes that we have previously shown are significantly regulated in hASC in response to this mechanical stimulus. Function analysis indicated that 10% cyclic tensile strain induced expression of genes associated with cell movement, cell proliferation, and tissue development, including development in musculoskeletal and cardiovascular systems. Our results demonstrate that hMSC from aged, osteoporotic donors are capable of enhanced osteogenic differentiation in response to 10% cyclic tensile strain with significant increases in the expression of genes associated with enhanced cell proliferation, musculoskeletal development, and angiogenesis. Surprisingly, cyclic tensile strain of magnitude 10% not only enhanced osteogenesis in hMSC from osteoporotic donors, but also enhanced expression of angiogenic factors. Better understanding and methodologies to promote osteogenesis in hMSC from elderly, osteoporotic donors may greatly facilitate achieving long-term success in bone regeneration and functional bone tissue engineering for this ever-growing patient population. C1 [Charoenpanich, Adisri; Wall, Michelle E.; Lalush, David S.; Loboa, Elizabeth G.] Univ N Carolina, Joint Dept Biomed Engn, Chapel Hill, NC USA. [Charoenpanich, Adisri; Wall, Michelle E.; Lalush, David S.; Loboa, Elizabeth G.] N Carolina State Univ, Raleigh, NC 27695 USA. [Tucker, Charles J.; Andrews, Danica M. K.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Dirschl, Douglas R.] Univ N Carolina, Dept Orthoped, Chapel Hill, NC USA. [Loboa, Elizabeth G.] N Carolina State Univ, Dept Mat Sci & Engn, Raleigh, NC 27695 USA. RP Loboa, EG (reprint author), N Carolina State Univ, UNC Chapel Hill, Joint Dept Biomed Engn, 4208B EB3,911 Oval Dr Campus Box 7115, Raleigh, NC 27695 USA. EM egloboa@ncsu.edu FU NIH, National Institute of Environmental Health Sciences; National Center for Research. Resources [10KR51023]; NIH/NIBIB [R03EB008790]; NSF/CBET [1133427] FX This research was supported, in part, by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, by the National Center for Research. Resources grant 10KR51023 (E. G. L.), by NIH/NIBIB grant R03EB008790 (E. G. L.), and by NSF/CBET grant 1133427 (E. G. L.). Excess human bone fragments were obtained from waste tissue from voluntary orthopedic surgeries at the UNC-CH hospital. Cell isolation, culture, mechanical loading, and PCR analysis were performed at the North Carolina State University. Microarray imaging and statistical analysis were performed at the National Institute of Environmental Health Sciences, NIH. NR 66 TC 9 Z9 10 U1 3 U2 21 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD JAN PY 2014 VL 20 IS 1-2 BP 67 EP 78 DI 10.1089/ten.tea.2013.0006 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA AI9TO UT WOS:000337280600007 PM 23927731 ER PT J AU Mohiuddin, MM Singh, AK Corcoran, PC Hoyt, RF Thomas, ML Lewis, BGT Eckhaus, M Dabkowski, NL Belli, AJ Reimann, KA Ayares, D Horvath, KA AF Mohiuddin, Muhammad M. Singh, Avneesh K. Corcoran, Philip C. Hoyt, Robert F. Thomas, Marvin L., III Lewis, Billeta G. T. Eckhaus, Michael Dabkowski, Nicole L. Belli, Aaron J. Reimann, Keith A. Ayares, David Horvath, Keith A. TI Role of anti-CD40 antibody-mediated costimulation blockade on non-Gal antibody production and heterotopic cardiac xenograft survival in a GTKO.hCD46Tg pig-to-baboon model SO XENOTRANSPLANTATION LA English DT Article DE 2C10R4; Anti-CD40 antibody; cardiac xenograft; CD46; Gal KO pigs; non-Gal antibodies; xenotransplantation ID LONG-TERM ACCEPTANCE; MONOCLONAL-ANTIBODY; NONHUMAN-PRIMATES; KIDNEY-TRANSPLANTATION; HYPERACUTE REJECTION; ALLOGRAFT SURVIVAL; TRANSGENIC PIG; BLOCKING CD40; CD28 PATHWAYS; XENOTRANSPLANTATION AB Background: Recently, we have shown that an immunosuppression regimen including costimulation blockade via anti-CD154 antibody significantly prolongs the cardiac xenograft survival in a GTKO.hCD46Tg pig-to-baboon heterotopic xenotransplantation model. Unfortunately, many coagulation disorders were observed with the use of anti-CD154 antibody, and recipient survival was markedly reduced by these complications. Material and Methods: In this experiment, we replaced anti-CD154 antibody with a more clinically acceptable anti-CD40 antibody while keeping the rest of the immunosuppressive regimen and the donor pig genetics the same. This was carried out to evaluate the antibody's role in xenograft survival and prevention of coagulopathies. Two available clones of anti-CD40 antibody were tested. One mouse anti-human CD40 antibody, (clone 3A8), activated B lymphocytes in vitro and only modestly suppressed antibody production in vivo. Whereas a recombinant mouse non-human primate chimeric raised against macaque CD40, (clone 2C10R4), blocked B-cell activation in vitro and completely blocked antibody production in vivo. Results: The thrombotic complications seen with anti-CD154 antibody were effectively avoided but the graft survival, although extended, was not as prolonged as observed with anti-CD154 antibody treatment. The longest survival for the 3A8 antibody group was 27 days, and the longest graft survival in the 2C10R4 antibody group was 146 days. All of the grafts except two rejected and were explanted. Only two recipient baboons had to be euthanized due to unrelated complications, and the rest of the baboons remained healthy throughout the graft survival period or after graft explantation. In contrast to our anti-CD 154 antibody- treated baboons, the non-Gal antibody levels started to rise after B cells made their appearance around 8 weeks post-transplantation. Conclusions: Anti-CD40 antibody at the current dose does not induce any coagulopathies but while effective, had reduced efficacy to induce similar long-term graft survival as with anti-CD154 antibody perhaps due to ineffective control of B-cell function and antibody production at the present dose. More experiments are required to determine antibody affinity and effective dose for inducing long-term cardiac xenograft survival. C1 [Mohiuddin, Muhammad M.; Singh, Avneesh K.; Corcoran, Philip C.; Horvath, Keith A.] NHLBI, Cardiothorac Surg Res Lab, NIH, Bethesda, MD 20892 USA. [Hoyt, Robert F.] NHLBI, Anim Program, NIH, Bethesda, MD 20892 USA. [Thomas, Marvin L., III; Lewis, Billeta G. T.; Eckhaus, Michael] NIH, Div Vet Resources, ORS, Bethesda, MD 20892 USA. [Dabkowski, Nicole L.; Belli, Aaron J.; Reimann, Keith A.] Univ Massachusetts, Sch Med, MassBiologics, Boston, MA 02125 USA. [Ayares, David] Revivicor Inc, Blacksburg, VA USA. RP Mohiuddin, MM (reprint author), NHLBI, CSRP, NIH, Bldg 10,Rm B1D47G,10 Ctr Dr,MSC 1550, Bethesda, MD 20892 USA. EM mohiuddinm@mail.nih.gov RI Mohiuddin, Muhammad/M-4642-2013; OI Mohiuddin, Muhammad/0000-0003-4654-783X; Belli, Aaron/0000-0002-9598-115X NR 32 TC 16 Z9 16 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN-FEB PY 2014 VL 21 IS 1 BP 35 EP 45 DI 10.1111/xen.12066 PG 11 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA AI9YC UT WOS:000337302500006 PM 24164510 ER PT J AU Milaneschi, Y Penninx, BWJH AF Milaneschi, Yuri Penninx, Brenda W. J. H. TI Depression in Older Persons with Mobility Limitations SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Depression; mobility; disability; elderly ID LIFE-STYLE INTERVENTIONS; PHYSICAL DECLINE; INFLAMMATORY MARKERS; MINOR DEPRESSION; MAJOR DEPRESSION; FUTURE-RESEARCH; RISK-FACTORS; DISABILITY; ADULTS; PREVALENCE AB The impact of depression on physical disability is undisputed. There is convincing evidence that depression increases the subsequent risk for physical disability and, in turn, physical disability results in increased depressive symptoms. Moreover, depression affects also the earlier stages of the disablement process (including functional limitation in mobility) and may accelerate the transitioning along the pathway to disability. Greater knowledge of the structure of this detrimental relationship and the underlying mechanisms should inform the clinical management of older persons at risk of physical decline and the development of effective interventions that break this downward spiral. C1 [Milaneschi, Yuri; Penninx, Brenda W. J. H.] VU Univ Med Center GGZ Geest, Dept Psychiat, NL-1081 HL Amsterdam, Netherlands. [Milaneschi, Yuri; Penninx, Brenda W. J. H.] VU Univ Med Center GGZ Geest, EMGO Inst Hlth & Care Res, NL-1081 HL Amsterdam, Netherlands. [Milaneschi, Yuri] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. [Penninx, Brenda W. J. H.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands. [Penninx, Brenda W. J. H.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands. RP Milaneschi, Y (reprint author), VU Univ Med Center GGZ Geest, Dept Psychiat, AJ Ernststr 1187, NL-1081 HL Amsterdam, Netherlands. EM y.milaneschi@ggzingeest.nl NR 59 TC 3 Z9 4 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2014 VL 20 IS 19 BP 3114 EP 3118 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AI7UB UT WOS:000337104200004 PM 24050170 ER PT J AU Maggio, M Lauretani, F De Vita, F Basaria, S Lippi, G Butto, V Luci, M Cattabiani, C Ceresini, G Verzicco, I Ferrucci, L Ceda, GP AF Maggio, Marcello Lauretani, Fulvio De Vita, Francesca Basaria, Shehzad Lippi, Giuseppe Butto, Valeria Luci, Michele Cattabiani, Chiara Ceresini, Graziano Verzicco, Ignazio Ferrucci, Luigi Ceda, Gian Paolo TI Multiple Hormonal Dysregulation as Determinant of Low Physical Performance and Mobility in Older Persons SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Multiple hormonal derangement; mobility; muscle function; older persons ID GROWTH-FACTOR-I; RANDOMIZED CONTROLLED-TRIAL; BONE-MINERAL DENSITY; SUBCLINICAL THYROID-DYSFUNCTION; SKELETAL-MUSCLE STRENGTH; VITAMIN-D INSUFFICIENCY; MYOFIBRILLAR PROTEIN-SYNTHESIS; SERUM 25-HYDROXYVITAMIN D; FACTOR BINDING PROTEIN-1; ENDOGENOUS SEX-HORMONES AB Mobility-disability is a common condition in older individuals. Many factors, including the age-related hormonal dysregulation, may concur to the development of disability in the elderly. In fact, during the aging process it is observed an imbalance between anabolic hormones that decrease (testosterone, dehydroepiandrosterone sulphate (DHEAS), estradiol, insulin like growth factor-1 (IGF-1) and Vitamin D) and catabolic hormones (cortisol, thyroid hormones) that increase. We start this review focusing on the mechanisms by which anabolic and catabolic hormones may affect physical performance and mobility. To address the role of the hormonal dysregulation to mobility-disability, we start to discuss the contribution of the single hormonal derangement. The studies used in this review were selected according to the period of time of publication, ranging from 2002 to 2013, and the age of the participants (>= 65 years). We devoted particular attention to the effects of anabolic hormones (DHEAS, testosterone, estradiol, Vitamin D and IGF-1) on both skeletal muscle mass and strength, as well as other objective indicators of physical performance. We also analyzed the reasons beyond the inconclusive data coming from RCTs using sex hormones, thyroid hormones, and vitamin D (dosage, duration of treatment, baseline hormonal values and reached hormonal levels). We finally hypothesized that the parallel decline of anabolic hormones has a higher impact than a single hormonal derangement on adverse mobility outcomes in older population. Given the multifactorial origin of low mobility, we underlined the need of future synergistic optional treatments (micronutrients and exercise) to improve the effectiveness of hormonal treatment and to safely ameliorate the anabolic hormonal status and mobility in older individuals. C1 [Maggio, Marcello; De Vita, Francesca; Butto, Valeria; Luci, Michele; Cattabiani, Chiara; Ceresini, Graziano; Verzicco, Ignazio; Ceda, Gian Paolo] Univ Parma, Dept Clin & Expt Med, Sect Geriatr, I-43100 Parma, Italy. [Maggio, Marcello; Lauretani, Fulvio; De Vita, Francesca; Ceresini, Graziano; Ceda, Gian Paolo] Univ Hosp Parma, Geriatr Rehabil Dept, Parma, Italy. [Basaria, Shehzad] Harvard Univ, Sch Med, Brigham & Womens Hosp, Res Program Mens Hlth Ageing & Metab, Cambridge, MA 02138 USA. [Lippi, Giuseppe] Univ Hosp Parma, Dipartimento Patol & Med Lab, Parma, Italy. [Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA. RP Maggio, M (reprint author), Dept Clin & Expt Med, Sect Geriatr, Via Gramsci 14, I-43100 Parma, Italy. EM marcellomag-gio2001@yahoo.it RI Lauretani, Fulvio/K-5115-2016; OI Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian Paolo/0000-0002-9648-8295 FU Intramural NIH HHS [ZIA AG001050-07] NR 255 TC 7 Z9 7 U1 2 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2014 VL 20 IS 19 BP 3119 EP 3148 PG 30 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AI7UB UT WOS:000337104200005 PM 24050169 ER PT J AU Ferrucci, L Baroni, M Ranchelli, A Lauretani, F Maggio, M Mecocci, P Ruggiero, C AF Ferrucci, L. Baroni, M. Ranchelli, A. Lauretani, F. Maggio, M. Mecocci, P. Ruggiero, C. TI Interaction Between Bone and Muscle in Older Persons with Mobility Limitations SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Bone-muscle; sarcopenia; osteoporosis; disability; aging ID AGE-RELATED-CHANGES; RANDOMIZED CONTROLLED-TRIAL; DIFFERENT SKELETAL SITES; MESENCHYMAL STEM-CELLS; HEALTHY POSTMENOPAUSAL WOMEN; VITAMIN-D SUPPLEMENTATION; LOWER-EXTREMITY FUNCTION; DWELLING ELDERLY-WOMEN; DIETARY-PROTEIN INTAKE; ESSENTIAL AMINO-ACIDS AB Aging is associated with a progressive loss of bone-muscle mass and strength. When the decline in mass and strength reaches critical thresholds associated with adverse health outcomes, they are operationally considered geriatric conditions and named, respectively, osteoporosis and sarcopenia. Osteoporosis and sarcopenia share many of the same risk factors and both directly or indirectly cause higher risk of mobility limitations, falls, fractures and disability in activities of daily living. This is not surprising since bones adapt their morphology and strength to the long-term loads exerted by muscle during anti-gravitational and physical activities. Non-mechanical systemic and local factors also modulate the mechanostat effect of muscle on bone by affecting the bidirectional osteocyte-muscle crosstalk, but the specific pathways that regulate these homeostatic mechanisms are not fully understood. More research is required to reach a consensus on cut points in bone and muscle parameters that identify individuals at high risk for adverse health outcomes, including falls, fractures and disability. A better understanding of the muscle-bone physiological interaction may help to develop preventive strategies that reduce the burden of musculoskeletal diseases, the consequent disability in older persons and to limit the financial burden associated with such conditions. In this review, we summarize age-related bone-muscle changes focusing on the biomechanical and homeostatic mechanisms that explain bone-muscle interaction and we speculate about possible pathological events that occur when these mechanisms become impaired. We also report some recent definitions of osteoporosis and sarcopenia that have emerged in the literature and their implications in clinical practice. Finally, we outline the current evidence for the efficacy of available anti-osteoporotic and proposed anti-sarcopenic interventions in older persons. C1 [Ferrucci, L.] NIA, Longitudinal Studies Sect, NIH, Baltimore, MD 21224 USA. [Baroni, M.; Ranchelli, A.; Ruggiero, C.] Univ Perugia, Dept Med, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. [Lauretani, F.; Maggio, M.; Mecocci, P.] Univ Parma, Dept Clin & Expt Med, Sect Geriatr, I-43100 Parma, Italy. RP Ruggiero, C (reprint author), Univ Perugia, Dept Med, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. EM ruggieroc07@hotmail.it RI Lauretani, Fulvio/K-5115-2016 OI Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS [ZIA AG001050-07] NR 347 TC 8 Z9 8 U1 5 U2 12 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2014 VL 20 IS 19 BP 3178 EP 3197 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AI7UB UT WOS:000337104200009 PM 24050165 ER PT J AU Rossi, AP Harris, TB Fantin, F Armellini, F Zamboni, M AF Rossi, Andrea P. Harris, Tamara B. Fantin, Francesco Armellini, Fabio Zamboni, Mauro TI The Multidomain Mobility Lab in Older Persons: From Bench to Bedside. The Assessment of Body Composition in Older Persons at Risk of Mobility Limitations SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Body composition; muscle mass; fat mass; imaging methods ID X-RAY ABSORPTIOMETRY; AIR-DISPLACEMENT PLETHYSMOGRAPHY; BIOELECTRICAL-IMPEDANCE ANALYSIS; SUBCUTANEOUS ADIPOSE-TISSUE; SKELETAL-MUSCLE MASS; FAT-FREE MASS; HEALTHY ELDERLY-WOMEN; WEIGHT CHANGE; COMPUTERIZED-TOMOGRAPHY; OBESE WOMEN AB With body composition it is possible to divide human body in compartments on the basis of different physical properties. The two level body composition model subdividing the whole body in fat mass and fat free mass is the most used in epidemiological and clinical studies in the elderly. Body composition techniques may be used to study ageing process. Changes in body composition occur as part of the normal ageing process and are associated with important effects on health and function. It has been shown that body composition changes with aging, with an increase in fat mass and a decrease in muscle mass, have important consequences on health and physical disability. Moreover body fat distribution changes with adverse metabolic profiles and increased cardiovascular risk. The purpose of this review is to describe the basic principles and techniques for fat free mass and fat mass evaluation, highlighting the advantages and limitations of different available body composition methods. C1 [Rossi, Andrea P.; Fantin, Francesco; Armellini, Fabio; Zamboni, Mauro] Univ Verona, Osped Maggiore, Cattedra Geriatria, I-37126 Verona, Italy. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Zamboni, M (reprint author), Univ Verona, Osped Maggiore, Cattedra Geriatria, Piazzale Stefani 1, I-37126 Verona, Italy. EM mauro.zamboni@univr.it OI ZAMBONI, Mauro/0000-0001-6961-9483 FU Intramural NIH HHS [ZIA AG007390-09] NR 114 TC 0 Z9 0 U1 1 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2014 VL 20 IS 19 BP 3245 EP 3255 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AI7UB UT WOS:000337104200013 PM 24050162 ER PT J AU Karev, GP Kareva, IG AF Karev, G. P. Kareva, I. G. TI Replicator Equations and Models of Biological Populations and Communities SO MATHEMATICAL MODELLING OF NATURAL PHENOMENA LA English DT Article DE population heterogeneity; replicator equation; selection system; tragedy of the commons; cancer ID NATURAL ROTIFER POPULATIONS; DYNAMICS; COMMONS; ADIPOSITY; MORTALITY; SELECTION; TRAGEDY AB An overview of a general approach for mathematical modeling of evolving heterogeneous populations using a wide class of selection systems and replicator equations (RE) is presented. The method allows visualizing evolutionary trajectories of evolving heterogeneous populations over time, while still enabling use of analytical tools of bifurcation theory. The developed theory involves introducing escort systems of auxiliary "keystone" variables, which reduce complex multi-dimensional inhomogeneous models to low dimensional systems of ODEs that in many cases can be investigated analytically. In addition to a comprehensive theoretical framework, a set of examples of the method's applicability to questions ranging from preventing the tragedy of the commons to cancer therapy is presented. C1 [Karev, G. P.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Kareva, I. G.] Floating Hosp Children, Tufts Med Ctr, Newman Lakka Inst Personalized Canc Care, Boston, MA 02111 USA. RP Karev, GP (reprint author), NIH, Natl Ctr Biotechnol Informat, Bldg 38A,Rm 5N511N,8600 Rockville Pike, Bethesda, MD 20894 USA. EM karev@ncbi.nlm.nih.gov FU NIH, NCBI; Office of Science (BER), U.S. Department of Energy [DE-SC0001434] FX G.K. was supported by the Intramural Research Program of the NIH, NCBI. I.K. was partially supported by the Office of Science (BER), U.S. Department of Energy, under Award Number DE-SC0001434 (to Philip Hahnfeldt, her postdoctoral fellowship mentor). NR 53 TC 4 Z9 5 U1 0 U2 6 PU EDP SCIENCES S A PI LES ULIS CEDEX A PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A, FRANCE SN 0973-5348 EI 1760-6101 J9 MATH MODEL NAT PHENO JI Math. Model. Nat. Phenom. PY 2014 VL 9 IS 3 BP 68 EP 95 DI 10.1051/mmnp/20149305 PG 28 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications; Multidisciplinary Sciences SC Mathematical & Computational Biology; Mathematics; Science & Technology - Other Topics GA AI6CQ UT WOS:000336957800005 ER PT J AU Varner, MW Silver, RM Hogue, CJR Willinger, M Parker, CB Thorsten, VR Goldenberg, RL Saade, GR Dudley, DJ Coustan, D Stoll, B Bukowski, R Koch, MA Conway, D Pinar, H Reddy, UM AF Varner, Michael W. Silver, Robert M. Hogue, Carol J. Rowland Willinger, Marian Parker, Corette B. Thorsten, Vanessa R. Goldenberg, Robert L. Saade, George R. Dudley, Donald J. Coustan, Donald Stoll, Barbara Bukowski, Radek Koch, Matthew A. Conway, Deborah Pinar, Halit Reddy, Uma M. CA Eunice Kennedy Shriver Natl Inst TI Association Between Stillbirth and Illicit Drug Use and Smoking During Pregnancy SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; PERINATAL OUTCOMES; UNITED-STATES; SERUM COTININE; FETAL-GROWTH; RISK-FACTORS; MARIJUANA USE; EXPOSURE; WOMEN; EPIDEMIOLOGY AB OBJECTIVE: To compare illicit drug and smoking use in pregnancies with and without stillbirth. METHODS: The Stillbirth Collaborative Research Network conducted a case-control study from March 2006 to September 2008, covering more than 90% of deliveries to residents of five a priori-defined geographically diverse regions. The study attempted to include all stillbirths and representative liveborn controls. Umbilical cord samples from cases and controls were collected and frozen for subsequent batch analysis. Maternal serum was collected at delivery and batch analyzed for cotinine. RESULTS: For 663 stillbirth deliveries, 418 (63%) had cord homogenate and 579 (87%) had maternal cotinine assays performed. For 1,932 live birth deliveries, 1,050 (54%) had cord homogenate toxicology and 1,545 (80%) had maternal cotinine assays performed. A positive cord homogenate test for any illicit drug was associated with stillbirth (odds ratio [OR] 1.94, 95% confidence interval [CI] 1.16-3.27). The most common individual drug was cannabis (OR 2.34 95% CI 1.13-4.81), although the effect was partially confounded by smoking. Both maternal self-reported smoking history and maternal serum cotinine levels were associated in a dose-response relationship with stillbirth. Positive serum cotinine less than 3 ng/mL and no reported history of smoking (proxy for passive smoke exposure) also were associated with stillbirth (OR 2.06, 95% CI 1.24-3.41). CONCLUSION: Cannabis use, smoking, illicit drug use, and apparent exposure to second-hand smoke, separately or in combination, during pregnancy were associated with an increased risk of stillbirth. Because cannabis use may be increasing with increased legalization, the relevance of these findings may increase as well. C1 Univ Utah, Hlth Sci Ctr, Salt Lake City, UT 84132 USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Atlanta, GA USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. RTI Int, Res Triangle Pk, NC USA. Columbia Univ, New York, NY USA. Univ Texas Med Branch Galveston, Galveston, TX USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. RP Varner, MW (reprint author), Univ Utah, Hlth Sci Ctr, Dept Obstet & Gynecol, 30 North 1900 East,Room 2B200, Salt Lake City, UT 84132 USA. EM Michael.varner@hsc.utah.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, National Institutes of Health [U10-HD045953, U10-HD045925, U10-HD045952, U10-HDO45955, U10-HD045944, U01-HD045954] FX Supported by grant funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health: U10-HD045953 (Brown University, Providence, Rhode Island); U10-HD045925 (Emory University, Atlanta, Georgia); U10-HD045952 (University of Texas Medical Branch at Galveston, Galveston, Texas); U10-HDO45955 (University of Texas Health Sciences Center at San Antonio, San Antonio, Texas); U10-HD045944 (University of Utah Health Sciences Center, Salt Lake City, Utah); and U01-HD045954 (RTI International, Research Triangle Park, North Carolina). NR 38 TC 28 Z9 29 U1 1 U2 10 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 JAN PY 2014 VL 123 IS 1 BP 113 EP 125 DI 10.1097/AOG.0000000000000052 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AI4AV UT WOS:000336808500017 PM 24463671 ER PT J AU Simoes, C Matos, MG Batista-Foguet, JM Simons-Morton, B AF Simoes, Celeste Matos, Margarida Gaspar Batista-Foguet, Joan M. Simons-Morton, Bruce TI Substance Use Across Adolescence: Do Gender and Age Matter? SO PSICOLOGIA-REFLEXAO E CRITICA LA English DT Article DE Adolescents; substance use; gender and age differences ID SMOKING; SCHOOL; PEER; POPULATION; BEHAVIOR; PARENTS; STRESS; HEALTH; STYLE AB Many of the choices which impact in lifetime health, such as substance use, are made in adolescence. It becomes, therefore, important to know the factors associated to these behaviours in adolescence in different contexts of life. To analyze these factors, an explanatory model was developed using structural equation modeling. Data from 12.881 state school students from Portugal who participated in two waves of the Health Behaviours in School-aged Children (HBSC) / World Health Organization (WHO) survey were analyzed. The model fits well the data [CFI: .985; NNFI: .980; RMSEA: .018 (.017-.020); SRMR: .018]. For each of the dependent factors, the levels of variance ranged from 12% (tobacco use) to 47% (alcohol and illicit drugs use). Alcohol and tobacco present the strongest associations to illicit drugs use. Relationships with family, friends, classmates, and teachers were also associated with substance use, being this association mediated by certain factors, including psychological symptoms, well-being, and school satisfaction. Several non-invariant paths were obtained in gender and age comparisons. The results showed that substance use is associated with several factors and that social factors are mediated by personal factors. Results have also shown that gender and age are important factors on substance use. C1 [Simoes, Celeste; Matos, Margarida Gaspar] Univ Lisbon, P-1699 Lisbon, Distrito De Lis, Portugal. [Batista-Foguet, Joan M.] Univ Ramon Llull, Barcelona, Spain. [Simons-Morton, Bruce] NICHHD, Bethesda, MD 20892 USA. RP Simoes, C (reprint author), Univ Lisbon, Fac Motricidade Humana, Estr Costa, P-1495688 Cruz Quebrada, Portugal. EM csimoes@fmh.ulisboa.pt; mmatos@fmh.ulisboa.pt; joanm.batista@esade.edu; mortonb@mail.nih.gov RI Batista Foguet, Joan Manuel/K-8670-2014; Gaspar de Matos, Margarida/H-3824-2012; OI Gaspar de Matos, Margarida/0000-0003-2114-2350; Simoes, Celeste/0000-0003-0229-1422; Simons-Morton, Bruce/0000-0003-1099-6617 NR 46 TC 1 Z9 1 U1 1 U2 7 PU UNIV FEDERAL RIO GRANDE SUL PI PORTO ALEGRE RS PA INST PSICOLOGIA, PPG EM PSICOLOGIA DA UFRGS, RUA RAMIRO BARCELOS 2600, PORTO ALEGRE RS, 90035-003, BRAZIL SN 0102-7972 J9 PSICOL-REFLEX CRIT JI Psicol.-Reflex. Crit. PY 2014 VL 27 IS 1 BP 179 EP 188 PG 10 WC Psychology, Multidisciplinary SC Psychology GA AI6EV UT WOS:000336964900020 ER PT S AU Haque, N Oberdoerffer, S AF Haque, Nazmul Oberdoerffer, Shalini BE Hertel, KJ TI Chromatin and Splicing SO SPLICEOSOMAL PRE-MRNA SPLICING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Alternative splicing; Chromatin; RNA polymerase II; Transcription; Epigenetics ID RNA-POLYMERASE-II; EXON-INTRON STRUCTURE; C-TERMINAL DOMAIN; DNA METHYLATION; GENOME-WIDE; HUMAN-CELLS; IN-VIVO; TRANSCRIPT ELONGATION; SITE SELECTION; U2 SNRNP AB In the past several years, the relationship between chromatin structure and mRNA processing has been the source of significant investigation across diverse disciplines. Central to these efforts was an unanticipated nonrandom distribution of chromatin marks across transcribed regions of protein-coding genes. In addition to the presence of specific histone modifications at the 5' and 3' ends of genes, exonic DNA was demonstrated to present a distinct chromatin landscape relative to intronic DNA. As splicing in higher eukaryotes predominantly occurs co-transcriptionally, these studies raised the possibility that chromatin modifications may aid the spliceosome in the detection of exons amidst vast stretches of noncoding intronic sequences. Recent investigations have supported a direct role for chromatin in splicing regulation and have suggested an intriguing role for splicing in the establishment of chromatin modifications. Here we will summarize an accumulating body of data that begins to reveal extensive coupling between chromatin structure and pre-mRNA splicing. C1 [Haque, Nazmul] NHLBI, Lab Ribonucleoprot Biochem, NIH, Bethesda, MD 20892 USA. [Oberdoerffer, Shalini] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Haque, N (reprint author), NHLBI, Lab Ribonucleoprot Biochem, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 104 TC 2 Z9 2 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-979-6; 978-1-62703-980-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1126 BP 97 EP 113 DI 10.1007/978-1-62703-980-2_7 D2 10.1007/978-1-62703-980-2 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BA3BZ UT WOS:000334100500008 PM 24549658 ER PT B AU Zhang, Y Choksi, S Liu, ZG AF Zhang, Yan Choksi, Swati Liu, Zhenggang BE Hayat, MA TI Autophagy is Required during Monocyte-Macrophage Differentiation SO AUTOPHAGY: CANCER, OTHER PATHOLOGIES, INFLAMMATION, IMMUNITY, INFECTION, AND AGING, VOL 2: ROLE IN GENERAL DISEASES LA English DT Article; Book Chapter ID HUMAN MONOCYTES/MACROPHAGES; MEDIATED CLEAVAGE; CELL-DEATH; ATG5; INFLAMMATION; APOPTOSIS; SURVIVAL; ADIPOGENESIS; MATURATION; INDUCTION AB Autophagy is a process that degrades superfluous or damaged macromolecules or organelles via the lysosome, and plays an important function in cellular homeostasis, development, survival, and differentiation. Our studies demonstrate a new function for autophagy during the differentiation of monocytes into macrophages. Monocytes are programmed to undergo apoptosis in the absence of stimulation. Stimuli that promote monocyte-macrophage differentiation prevent the apoptosis of monocytes. We found that autophagy is induced when monocytes are triggered to differentiate, and that the induction of autophagy is pivotal for the survival and differentiation of monocytes. Inhibition of autophagy by pharmacologic inhibitors or siRNA approaches resulted in apoptosis of the cells that are engaged in differentiation. A differentiation signal releases Beclin 1 from Bcl-2 by activating JNK and blocks Atg5 cleavage, both of which are critical for the induction of autophagy. Others have shown that the in vivo differentiation of monocytes from Atg7(-/-) deficient mice into macrophages was drastically inhibited compared with monocytes from control littermates. Our data also show that preventing autophagy induction hampers differentiation and cytokine production. These findings highlight an essential role of autophagy during monocyte differentiation and the acquisition of macrophage functions. C1 [Zhang, Yan; Choksi, Swati; Liu, Zhenggang] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Zhang, Y (reprint author), NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 35 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-411514-9; 978-0-12-405877-4 PY 2014 BP 227 EP 238 DI 10.1016/B978-0-12-405877-4.00015-9 PG 12 WC Cell Biology; Pathology SC Cell Biology; Pathology GA BHP61 UT WOS:000326264800016 ER PT J AU Skoura, E Datseris, IE Xekouki, P Tolis, G Stratakis, CA AF Skoura, Evangelia Datseris, Ioannis E. Xekouki, Paraskevi Tolis, Georgios Stratakis, Constantine A. TI SPECT and F-18-FDG PET/CT Imaging of Multiple Paragangliomas and a Growth Hormone-Producing Pituitary Adenoma as Phenotypes From a Novel Succinate Dehydrogenase Subunit D Mutation SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE succinate dehydrogenase (SDH); paragangliomas; I-123-MIBG; In-111-pentetreotide; F-18-FDG ID PHEOCHROMOCYTOMA; TUMORS; SDH C1 [Skoura, Evangelia; Datseris, Ioannis E.] Evangelismos Gen Hosp, Dept Nucl Med, Athens 10676, Greece. [Xekouki, Paraskevi; Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Tolis, Georgios] Hippocrate Gen Hosp, Div Endocrinol & Metab, Athens, Greece. RP Skoura, E (reprint author), Evangelismos Gen Hosp, Dept Nucl Med, 45-47 Ipsilantou St, Athens 10676, Greece. EM lskoura@yahoo.gr NR 8 TC 1 Z9 1 U1 0 U2 4 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 JAN PY 2014 VL 39 IS 1 BP 81 EP 83 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI3CT UT WOS:000336737300050 PM 24152617 ER PT S AU Sethi, AJ Angerer, RC Angerer, LM AF Sethi, Aditya J. Angerer, Robert C. Angerer, Lynne M. BE Carroll, DJ Stricker, SA TI Multicolor Labeling in Developmental Gene Regulatory Network Analysis SO DEVELOPMENTAL BIOLOGY OF THE SEA URCHIN AND OTHER MARINE INVERTEBRATES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE TSA Plus; Digoxigenin; Fluorescein; Lineage; Signaling; Linkages; Marker; Perturbations ID SEA-URCHIN EMBRYO; IN-SITU HYBRIDIZATION; ENDOMESODERM NETWORK; SPECIFICATION; EXPRESSION; AXIS AB The sea urchin embryo is an important model system for developmental gene regulatory network (GRN) analysis. This chapter describes the use of multicolor fluorescent in situ hybridization (FISH) as well as a combination of FISH and immunohistochemistry in sea urchin embryonic GRN studies. The methods presented here can be applied to a variety of experimental settings where accurate spatial resolution of multiple gene products is required for constructing a developmental GRN. C1 [Sethi, Aditya J.; Angerer, Robert C.; Angerer, Lynne M.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Sethi, AJ (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA DE000712-10] NR 22 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-974-1; 978-1-62703-973-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1128 BP 249 EP 262 DI 10.1007/978-1-62703-974-1_17 D2 10.1007/978-1-62703-974-1 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Developmental Biology SC Biochemistry & Molecular Biology; Developmental Biology GA BA2XV UT WOS:000333984100018 PM 24567220 ER PT J AU Saeed, F Hoffert, JD Knepper, MA AF Saeed, Fahad Hoffert, Jason D. Knepper, Mark A. TI CAMS-RS: Clustering Algorithm for Large-Scale Mass Spectrometry Data Using Restricted Search Space and Intelligent Random Sampling SO IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS LA English DT Article; Proceedings Paper CT 24th International Conference on Genome Informatics (GIW) CY DEC 16-18, 2013 CL Singapore, SINGAPORE DE Mass spectrometry; clustering; proteomics; search space ID SPECTRA; IDENTIFICATION; PROTEOMICS; STRATEGY AB High-throughput mass spectrometers can produce massive amounts of redundant data at an astonishing rate with many of them having poor signal-to-noise (S/N) ratio. These low S/N ratio spectra may not get interpreted using conventional spectra-to-database matching techniques. In this paper, we present an efficient algorithm, CAMS-RS (Clustering Algorithm for Mass Spectra using Restricted Space and Sampling) for clustering of raw mass spectrometry data. CAMS-RS utilizes a novel metric (called F-set) that exploits the temporal and spatial patterns to accurately assess similarity between two given spectra. The F-set similarity metric is independent of the retention time and allows clustering of mass spectrometry data from independent LC-MS/MS runs. A novel restricted search space strategy is devised to limit the comparisons of the number of spectra. An intelligent sampling method is executed on individual bins that allow merging of the results to make the final clusters. Our experiments, using experimentally generated data sets, show that the proposed algorithm is able to cluster spectra with high accuracy and is helpful in interpreting low S/N ratio spectra. The CAMS-RS algorithm is highly scalable with increasing number of spectra and our implementation allows clustering of up to a million spectra within minutes. C1 [Saeed, Fahad; Hoffert, Jason D.; Knepper, Mark A.] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20895 USA. RP Saeed, F (reprint author), NHLBI, Epithelial Syst Biol Lab, NIH, 10 Ctr Dr,6N312,MSC 1603, Bethesda, MD 20895 USA. EM fahad.saeed@nih.gov FU operating budget of Division of Intramural Research, National Heart, Lung and Blood Institute; National Institutes of Health (NIH) [ZO1-HL001285] FX This work was funded by the operating budget of Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health (NIH), Project ZO1-HL001285. All the Mass Spectrometry data was produced at Proteomics Core at System Biology Center, NHLBI, NIH. NR 33 TC 5 Z9 5 U1 1 U2 8 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 1545-5963 EI 1557-9964 J9 IEEE ACM T COMPUT BI JI IEEE-ACM Trans. Comput. Biol. Bioinform. PD JAN-FEB PY 2014 VL 11 IS 1 BP 128 EP 141 DI 10.1109/TCBB.2013.152 PG 14 WC Biochemical Research Methods; Computer Science, Interdisciplinary Applications; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Biochemistry & Molecular Biology; Computer Science; Mathematics GA AI2AX UT WOS:000336659800014 PM 26355513 ER PT J AU Begg, MD Crumley, G Fair, AM Martina, CA McCormack, WT Merchant, C Patino-Sutton, CM Umans, JG AF Begg, Melissa D. Crumley, Gene Fair, Alecia M. Martina, Camille A. McCormack, Wayne T. Merchant, Carol Patino-Sutton, Cecilia M. Umans, Jason G. TI Approaches to Preparing Young Scholars for Careers in Interdisciplinary Team Science SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article ID DECISION-MAKING; TRANSDISCIPLINARY RESEARCH; COLLABORATION; PATTERNS C1 [Begg, Melissa D.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Begg, Melissa D.] Columbia Univ, Irving Inst Clin & Translat Res, New York, NY USA. [Crumley, Gene] Univ Calif Davis, Davis, CA 95616 USA. [Fair, Alecia M.] Vanderbilt Univ, Vanderbilt Inst Clin Translat Res, Res Support Serv, Nashville, TN 37235 USA. [Martina, Camille A.] Univ Rochester, Sch Med & Dent, Dept Publ Hlth Sci & Environm Med, Rochester, NY USA. [McCormack, Wayne T.] Univ Florida, Clin & Translat Sci Inst, Clin Training Program, Gainesville, FL USA. [McCormack, Wayne T.] Univ Florida, Clin & Translat Sci Inst, Translat Sci Predoctoral Training Program, Gainesville, FL USA. [McCormack, Wayne T.] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL USA. [Merchant, Carol] NIH, Common Fund Career Dev Programs, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Patino-Sutton, Cecilia M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Umans, Jason G.] Georgetown Univ, MedStar Hlth Res Inst, Hyattsville, MD USA. [Umans, Jason G.] Georgetown Univ, Div Nephrol & Hypertens, Washington, DC USA. RP Begg, MD (reprint author), Mailman Sch Publ Hlth, Irving Inst Clin & Translat Res, Off Dean, 722 W 168th St,Room 1411A, New York, NY 10032 USA. EM mdb3@columbia.edu OI McCormack, Wayne/0000-0002-2117-8727 FU NCATS NIH HHS [UL1 TR000042, UL1 TR000002, UL1 TR000040, UL1 TR000064, UL1 TR000101, UL1 TR000130, UL1 TR000445, UL1TR000002, UL1TR000040, UL1TR000042, UL1TR000064, UL1TR000101, UL1TR000445, ULT1TR000130] NR 33 TC 10 Z9 10 U1 3 U2 9 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 JAN PY 2014 VL 62 IS 1 BP 14 EP 25 PG 12 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AH7AP UT WOS:000336284900001 PM 24169319 ER PT J AU Huser, V Cimino, JJ AF Huser, Vojtech Cimino, James J. TI Don't take your EHR to heaven, donate it to science: legal and research policies for EHR post mortem SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID BIOBANK; CARE AB Recently, an important public debate emerged about the digital afterlife of any personal data stored in the cloud. Such debate brings also to attention the importance of transparent management of electronic health record (EHR) data of deceased patients. In this perspective paper, we look at legal and regulatory policies for EHR data post mortem. We analyze observational research situations using EHR data that do not require institutional review board approval. We propose creation of a deceased subject integrated data repository (dsIDR) as an effective tool for piloting certain types of research projects. We highlight several dsIDR challenges in proving death status, informed consent, obtaining data from payers and healthcare providers and the involvement of next of kin. C1 [Huser, Vojtech; Cimino, James J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA. RP Huser, V (reprint author), NIH, Lab Informat Dev, Ctr Clin, 10 Ctr Dr,Rm 10-6-5561, Bethesda, MD 20892 USA. EM vojtech.huser@nih.gov OI Cimino, James/0000-0003-4101-1622 FU National Institutes of Health Clinical Center; National Library of Medicine FX This research was supported by the Intramural Research Program of the National Institutes of Health Clinical Center and the National Library of Medicine. NR 13 TC 3 Z9 3 U1 1 U2 7 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 JAN PY 2014 VL 21 IS 1 BP 8 EP 12 DI 10.1136/amiajnl-2013-002061 PG 5 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 AI2VK UT WOS:000336716000002 PM 23966483 ER PT J AU Goldbach, H Chang, AY Kyer, A Ketshogileng, D Taylor, L Chandra, A Dacso, M Kung, SJ Rijken, T Fontelo, P Littman-Quinn, R Seymour, AK Kovarik, CL AF Goldbach, Hayley Chang, Aileen Y. Kyer, Andrea Ketshogileng, Dineo Taylor, Lynne Chandra, Amit Dacso, Matthew Kung, Shiang-Ju Rijken, Taatske Fontelo, Paul Littman-Quinn, Ryan Seymour, Anne K. Kovarik, Carrie L. TI Evaluation of generic medical information accessed via mobile phones at the point of care in resource-limited settings SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID DEVELOPING-COUNTRIES; HEALTH; WORKERS; TRIAL AB Objective Many mobile phone resources have been developed to increase access to health education in the developing world, yet few studies have compared these resources or quantified their performance in a resource-limited setting. This study aims to compare the performance of resident physicians in answering clinical scenarios using PubMed abstracts accessed via the PubMed for Handhelds (PubMed4Hh) website versus medical/drug reference applications (Medical Apps) accessed via software on the mobile phone. Methods A two-arm comparative study with crossover design was conducted. Subjects, who were resident physicians at the University of Botswana, completed eight scenarios, each with multi-part questions. The primary outcome was a grade for each question. The primary independent variable was the intervention arm and other independent variables included residency and question. Results Within each question type there were significant differences in 'percentage correct' between Medical Apps and PubMed4Hh for three of the six types of questions: drug-related, diagnosis/definitions, and treatment/management. Within each of these question types, Medical Apps had a higher percentage of fully correct responses than PubMed4Hh (63% vs 13%, 33% vs 12%, and 41% vs 13%, respectively). PubMed4Hh performed better for epidemiologic questions. Conclusions While mobile access to primary literature remains important and serves an information niche, mobile applications with condensed content may be more appropriate for point-of-care information needs. Further research is required to examine the specific information needs of clinicians in resource-limited settings and to evaluate the appropriateness of current resources in bridging location-and context-specific information gaps. C1 [Goldbach, Hayley; Taylor, Lynne; Kovarik, Carrie L.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Goldbach, Hayley; Chang, Aileen Y.; Littman-Quinn, Ryan; Seymour, Anne K.; Kovarik, Carrie L.] Botswana UPenn Partnership, Gaborone, Botswana. [Chang, Aileen Y.; Kovarik, Carrie L.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Kyer, Andrea; Seymour, Anne K.] Univ Penn, Biomed Lib, Philadelphia, PA 19104 USA. [Ketshogileng, Dineo] Univ Botswana Lib, Gaborone, Botswana. [Taylor, Lynne] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Chandra, Amit; Kung, Shiang-Ju; Rijken, Taatske] Univ Botswana, Sch Med, Gaborone, Botswana. [Dacso, Matthew] Univ Texas Med Branch, Ctr Global Hlth Educ, Galveston, TX 77555 USA. [Kung, Shiang-Ju] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Fontelo, Paul] Natl Lib Med, Bethesda, MD USA. RP Kovarik, CL (reprint author), Univ Penn, Dept Dermatol, 3600 Spruce St,2 Maloney Bldg, Philadelphia, PA 19104 USA. EM carrie.kovarik@uphs.upenn.edu RI Emchi, Karma/Q-1952-2016 FU National Library of Medicine at the National Institutes of Health, USA FX This study was funded in part by the National Library of Medicine at the National Institutes of Health, USA. NR 36 TC 6 Z9 6 U1 2 U2 15 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 JAN PY 2014 VL 21 IS 1 BP 37 EP 42 DI 10.1136/amiajnl-2012-001276 PG 6 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 AI2VK UT WOS:000336716000008 PM 23535665 ER PT S AU Wu, XF Zheng, YL Hsu, TC AF Wu, Xifeng Zheng, Yun-Ling Hsu, T. C. BE Keohavong, P Grant, SG TI Mutagen Sensitivity as Measured by Induced Chromatid Breakage as a Marker of Cancer Risk SO MOLECULAR TOXICOLOGY PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Mutagen sensitivity; Chromatid breaks; Cancer susceptibility; Bleomycin; Benzopyrene; Nitroquinoline; gamma-irradiation ID UPPER AERODIGESTIVE TRACT; SQUAMOUS-CELL CARCINOMA; IN-VITRO SENSITIVITY; DIOL-EPOXIDE; BREAST-CANCER; BIOLOGICAL MARKER; NECK-CANCER; BLEOMYCIN; SUSCEPTIBILITY; HEAD AB Risk assessment is now recognized as a multidisciplinary process, extending beyond the scope of traditional epidemiologic methodology to include biological evaluation of interindividual differences in carcinogenic susceptibility. Modulation of environmental exposures by host genetic factors may explain much of the observed interindividual variation in susceptibility to carcinogenesis. These genetic factors include, but are not limited to, carcinogen metabolism and DNA repair capacity. This chapter describes a standardized method for the functional assessment of mutagen sensitivity. This in vitro assay measures the frequency of mutagen-induced breaks in the chromosomes of peripheral blood lymphocytes. Mutagen sensitivity assessed by this method has been shown to be a significant risk factor for tobacco-related maladies, especially those of the upper aerodigestive tract. Mutagen sensitivity may therefore be a useful member of a panel of susceptibility markers for defining high-risk subgroups for chemoprevention trials. This chapter describes methods for and discusses results from studies of mutagen sensitivity as measured by quantifying chromatid breaks induced by clastogenic agents, such as the gamma-radiation mimetic DNA cross-linking agent bleomycin and chemicals that form so-called bulky DNA adducts, such as 4-nitroquinoline and the tobacco smoke constituent benzo[a] pyrene, in short-term cultured peripheral blood lymphocytes. C1 [Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Zheng, Yun-Ling] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. [Hsu, T. C.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. RP Wu, XF (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. NR 32 TC 1 Z9 1 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-739-6; 978-1-62703-738-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1105 BP 183 EP 192 DI 10.1007/978-1-62703-739-6_15 D2 10.1007/978-1-62703-739-6 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA BA2SX UT WOS:000333851000016 PM 24623229 ER PT S AU Furda, A Santos, JH Meyer, JN Van Houten, B AF Furda, Amy Santos, Janine H. Meyer, Joel N. Van Houten, Bennett BE Keohavong, P Grant, SG TI Quantitative PCR-Based Measurement of Nuclear and Mitochondrial DNA Damage and Repair in Mammalian Cells SO MOLECULAR TOXICOLOGY PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Mitochondrial DNA; Nuclear DNA; DNA damage; Reactive oxygen species (ROS); Quantitative PCR (QPCR) ID NUCLEOTIDE EXCISION-REPAIR; RETINAL-PIGMENT EPITHELIUM; POLYMERASE-CHAIN-REACTION; ENDOGENOUS OXIDATIVE DAMAGE; SMOOTH-MUSCLE-CELLS; HYDROGEN-PEROXIDE; ESCHERICHIA-COLI; COPY NUMBER; GENOMIC DNA; HUMAN BRAIN AB In this chapter, we describe a gene-specific quantitative PCR (QPCR)-based assay for the measurement of DNA damage, using amplification of long DNA targets. This assay has been used extensively to measure the integrity of both nuclear and mitochondrial genomes exposed to different genotoxins and has proven to be particularly valuable in identifying reactive oxygen species-mediated mitochondrial DNA damage. QPCR can be used to quantify both the formation of DNA damage as well as the kinetics of damage removal. One of the main strengths of the assay is that it permits monitoring the integrity of mtDNA directly from total cellular DNA without the need for isolating mitochondria or a separate step of mitochondrial DNA purification. Here we discuss advantages and limitations of using QPCR to assay DNA damage in mammalian cells. In addition, we give a detailed protocol of the QPCR assay that helps facilitate its successful deployment in any molecular biology laboratory. C1 [Furda, Amy; Van Houten, Bennett] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15260 USA. [Santos, Janine H.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. [Santos, Janine H.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. [Meyer, Joel N.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA. RP Furda, A (reprint author), Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15260 USA. FU NIEHS NIH HHS [R01 ES017540] NR 78 TC 15 Z9 15 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-739-6; 978-1-62703-738-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1105 BP 419 EP 437 DI 10.1007/978-1-62703-739-6_31 D2 10.1007/978-1-62703-739-6 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA BA2SX UT WOS:000333851000032 PM 24623245 ER PT S AU Stahl, SJ Watts, NR Wingfield, PT AF Stahl, Stephen J. Watts, Norman R. Wingfield, Paul T. BE Ossipow, V Fischer, N TI Generation and Use of Antibody Fragments for Structural Studies of Proteins Refractory to Crystallization SO MONOCLONAL ANTIBODIES: METHODS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Fab; scFv; Phage-display; Crystallization; Chaperone; HIV; Rev ID HIV-1 REV PROTEIN; MEMBRANE-PROTEINS; EXPORT AB With the rapid technological advances in all aspects of macromolecular X-ray crystallography the preparation of diffraction quality crystals has become the rate-limiting step. Crystallization chaperones have proven effective for overcoming this barrier. Here we describe the usage of a Fab chaperone for the crystallization of HIV-1 Rev, a protein that has long resisted all attempts at elucidating its complete atomic structure. C1 [Stahl, Stephen J.; Watts, Norman R.; Wingfield, Paul T.] NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. RP Stahl, SJ (reprint author), NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA AR041115-18] NR 19 TC 0 Z9 0 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-992-5; 978-1-62703-991-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1131 BP 549 EP 561 DI 10.1007/978-1-62703-992-5_35 D2 10.1007/978-1-62703-992-5 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA2SY UT WOS:000333851100036 PM 24515490 ER PT J AU Popuri, V Hsu, J Khadka, P Horvath, K Liu, Y Croteau, DL Bohr, VA AF Popuri, Venkateswarlu Hsu, Joseph Khadka, Prabhat Horvath, Kent Liu, Yie Croteau, Deborah L. Bohr, Vilhelm A. TI Human RECQL1 participates in telomere maintenance SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ROTHMUND-THOMSON SYNDROME; WERNER-SYNDROME HELICASE; MOBILE D-LOOPS; REPLICATION FORK; DNA-DAMAGE; FRAGILE SITES; BLM HELICASE; HUMAN POT1; T-LOOP; TRF2 AB A variety of human tumors employ alternative and recombination-mediated lengthening for telomere maintenance (ALT). Human RecQ helicases, such as BLM and WRN, can efficiently unwind alternate/secondary structures during telomere replication and/or recombination. Here, we report a novel role for RECQL1, the most abundant human RecQ helicase but functionally least studied, in telomere maintenance. RECQL1 associates with telomeres in ALT cells and actively resolves telomeric D-loops and Holliday junction substrates. RECQL1 physically and functionally interacts with telomere repeat-binding factor 2 that in turn regulates its helicase activity on telomeric substrates. The telomeric single-stranded binding protein, protection of telomeres 1 efficiently stimulates RECQL1 on telomeric substrates containing thymine glycol, a replicative blocking lesion. Loss of RECQL1 results in dysfunctional telomeres, telomere loss and telomere shortening, elevation of telomere sister-chromatid exchanges and increased aphidicolin-induced telomere fragility, indicating a role for RECQL1 in telomere maintenance. Further, our results indicate that RECQL1 may participate in the same pathway as WRN, probably in telomere replication. C1 [Popuri, Venkateswarlu; Hsu, Joseph; Khadka, Prabhat; Horvath, Kent; Liu, Yie; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM vbohr@nih.gov RI Hsu, Joseph Kuang-Wu/N-2847-2013 FU Intramural Research Program of the National Institute on Aging (NIH) [AG000726-20]; NIH Intramural Program FX Intramural Research Program of the National Institute on Aging (NIH) [AG000726-20]. Funding for open access charge: NIH Intramural Program. NR 71 TC 16 Z9 16 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 9 BP 5671 EP 5688 DI 10.1093/nar/gku200 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH9WI UT WOS:000336495400031 PM 24623817 ER PT J AU Parks, AR Court, C Lubkowska, L Jin, DJ Kashlev, M Court, DL AF Parks, Adam R. Court, Carolyn Lubkowska, Lucyna Jin, Ding J. Kashlev, Mikhail Court, Donald L. TI Bacteriophage lambda N protein inhibits transcription slippage by Escherichia coli RNA polymerase SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA HYBRID; ELONGATION COMPLEX; TRANSLATION REPRESSION; GENE-EXPRESSION; RPOB MUTATIONS; PHAGE-LAMBDA; ANTITERMINATION; TERMINATION; RESISTANT; PROCESSIVITY AB Transcriptional slippage is a class of error in which ribonucleic acid (RNA) polymerase incorporates nucleotides out of register, with respect to the deoxyribonucleic acid (DNA) template. This phenomenon is involved in gene regulation mechanisms and in the development of diverse diseases. The bacteriophage lambda N protein reduces transcriptional slippage within actively growing cells and in vitro. N appears to stabilize the RNA/DNA hybrid, particularly at the 5' end, preventing loss of register between transcript and template. This report provides the first evidence of a protein that directly influences transcriptional slippage, and provides a clue about the molecular mechanism of transcription termination and N-mediated antitermination. C1 [Parks, Adam R.; Court, Carolyn; Lubkowska, Lucyna; Jin, Ding J.; Kashlev, Mikhail; Court, Donald L.] NCI, Mol Control & Genet Sect, NIH, Frederick, MD 21702 USA. RP Court, DL (reprint author), NCI, Mol Control & Genet Sect, NIH, Frederick, MD 21702 USA. EM courtd@mail.nih.gov FU National Institutes of Health at National Cancer Institute's Center for Cancer Research; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX Intramural Research Program of the National Institutes of Health at National Cancer Institute's Center for Cancer Research; National Cancer Institute, National Institutes of Health [HHSN261200800001E]. Funding for open access charge: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 40 TC 9 Z9 10 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2014 VL 42 IS 9 BP 5823 EP 5829 DI 10.1093/nar/gku203 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH9WI UT WOS:000336495400043 PM 24711367 ER PT S AU Groft, SC AF Groft, Stephen C. BE Bali, RK Bos, L Gibbons, MC Ibell, SR TI Rare Diseases in the Age of Health 2.0 Foreword SO RARE DISEASES IN THE AGE OF HEALTH 2.0 SE Communications in Medical and Care Compunetics LA English DT Editorial Material; Book Chapter C1 NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, US Dept HHS, Bethesda, MD 20892 USA. RP Groft, SC (reprint author), NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, US Dept HHS, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 2191-3811 BN 978-3-642-38643-5; 978-3-642-38642-8 J9 COMMUN MED CARE COMP PY 2014 VL 4 BP IX EP X D2 10.1007/978-3-642-38643-5 PG 2 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA BA1ZV UT WOS:000333205300001 ER PT S AU Gopal-Srivastava, R Groft, SC AF Gopal-Srivastava, Rashmi Groft, Stephen C. BE Bali, RK Bos, L Gibbons, MC Ibell, SR TI Rare Diseases Challenges and Opportunities SO RARE DISEASES IN THE AGE OF HEALTH 2.0 SE Communications in Medical and Care Compunetics LA English DT Article; Book Chapter ID REGISTRY AB Rare diseases present special challenges to the rare diseases community. The community includes research investigators, clinicians, funding organizations in the public and private sectors, patient advocacy groups, the biopharmaceutical and medical device industries and the regulatory agencies. C1 [Gopal-Srivastava, Rashmi; Groft, Stephen C.] NIH, ORDR, NCATS, Bethesda, MD 20892 USA. RP Gopal-Srivastava, R (reprint author), NIH, ORDR, NCATS, Democracy 1 Bldg,Room 1008,6701 Democracy Blvd, Bethesda, MD 20892 USA. EM Rashmi.Gopal-Srivastava@nih.gov NR 5 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 2191-3811 BN 978-3-642-38643-5; 978-3-642-38642-8 J9 COMMUN MED CARE COMP PY 2014 VL 4 BP 283 EP 290 DI 10.1007/978-3-642-38643-5_29 D2 10.1007/978-3-642-38643-5 PG 8 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA BA1ZV UT WOS:000333205300031 ER PT J AU Mills, KL Lalonde, F Clasen, LS Giedd, JN Blakemore, SJ AF Mills, Kathryn L. Lalonde, Francois Clasen, Liv S. Giedd, Jay N. Blakemore, Sarah-Jayne TI Developmental changes in the structure of the social brain in late childhood and adolescence SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE adolescence; brain development; MRI; social cognition; mentalizing ID HUMAN CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; CORTICAL SURFACE; GEOMETRICALLY ACCURATE; GENETIC INFLUENCES; PREFRONTAL CORTEX; COORDINATE SYSTEM; NEURAL BASES; MRI; MATURATION AB Social cognition provides humans with the necessary skills to understand and interact with one another. One aspect of social cognition, mentalizing, is associated with a network of brain regions often referred to as the 'social brain.' These consist of medial prefrontal cortex [medial Brodmann Area 10 (mBA10)], temporoparietal junction (TPJ), posterior superior temporal sulcus (pSTS) and anterior temporal cortex (ATC). How these specific regions develop structurally across late childhood and adolescence is not well established. This study examined the structural developmental trajectories of social brain regions in the longest ongoing longitudinal neuroimaging study of human brain maturation. Structural trajectories of grey matter volume, cortical thickness and surface area were analyzed using surface-based cortical reconstruction software and mixed modeling in a longitudinal sample of 288 participants (ages 7-30 years, 857 total scans). Grey matter volume and cortical thickness in mBA10, TPJ and pSTS decreased from childhood into the early twenties. The ATC increased in grey matter volume until adolescence and in cortical thickness until early adulthood. Surface area for each region followed a cubic trajectory, peaking in early or pre-adolescence before decreasing into the early twenties. These results are discussed in the context of developmental changes in social cognition across adolescence. C1 [Mills, Kathryn L.; Blakemore, Sarah-Jayne] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. [Mills, Kathryn L.; Lalonde, Francois; Clasen, Liv S.; Giedd, Jay N.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Mills, KL (reprint author), UCL Inst Cognit Neurosci, 17 Queen Sq, London WC1N 3AR, England. EM kathryn.l.mills@gmail.com RI Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-2002-8978 FU National Institutes of Health; National Institute of Mental Health Intramural Research Program; NIH Graduate Partnership Program; Royal Society University Research Fellowship FX This study was supported by the National Institutes of Health, National Institute of Mental Health Intramural Research Program and the NIH Graduate Partnership Program. S.J.B. is funded by a Royal Society University Research Fellowship. NR 77 TC 46 Z9 46 U1 15 U2 49 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD JAN PY 2014 VL 9 IS 1 BP 123 EP 131 DI 10.1093/scan/nss113 PG 9 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AH9TY UT WOS:000336487400016 PM 23051898 ER PT S AU Rajashankar, K Dauter, Z AF Rajashankar, Kanagalaghatta Dauter, Zbigniew BE Anderson, WF TI Data Collection for Crystallographic Structure Determination SO STRUCTURAL GENOMICS AND DRUG DISCOVERY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Diffraction data collection; Diffraction data quality; Rotation method; Strategy ID MACROMOLECULAR CRYSTALLOGRAPHY; RADIATION-DAMAGE; STRATEGIES; QUALITY AB Diffraction data measurement is the final experimental step of crystal structure analysis; all subsequent stages are computational. Good-quality data, optimized for a particular application, make the structure solution and refinement easier and enhance the accuracy of the final models. This chapter describes the principles of the rotation method of data collection and discusses various scenarios that are useful for different types of applications, such as anomalous phasing, molecular replacement, ligand identification, etc. Some typical problems encountered in practice are also discussed. C1 [Rajashankar, Kanagalaghatta] Cornell Univ, Argonne Natl Lab, NE CAT, Argonne, IL 60439 USA. [Rajashankar, Kanagalaghatta] Cornell Univ, Argonne Natl Lab, Dept Chem & Chem Biol, Argonne, IL USA. [Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne Natl Lab, Argonne, IL USA. RP Rajashankar, K (reprint author), Cornell Univ, Argonne Natl Lab, NE CAT, Argonne, IL 60439 USA. FU Intramural NIH HHS; NIGMS NIH HHS [8 P41 GM103403-10] NR 24 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0354-2; 978-1-4939-0353-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1140 BP 211 EP 237 DI 10.1007/978-1-4939-0354-2_17 D2 10.1007/978-1-4939-0354-2 PG 27 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BA2NQ UT WOS:000333708800018 PM 24590721 ER PT J AU Brooke, CB AF Brooke, Christopher B. TI Biological activities of 'noninfectious' influenza A virus particles SO FUTURE VIROLOGY LA English DT Review DE aggregation; DI particles; genome packaging; influenza; noninfectious; semi-infectious; virion heterogeneity; virus ID DEFECTIVE-INTERFERING PARTICLES; GENOMIC RNA SEGMENTS; WEST-NILE-VIRUS; INFECTED-CELLS; RESPIRATORY DROPLET; VIRAL-RNA; RIBONUCLEOPROTEIN COMPLEXES; PRIMARY TRANSCRIPTION; MUTATION-RATES; IN-VIVO AB Only a small fraction of influenza A virus (IAV) particles within a viral population register as infectious by traditional infectivity assays. Despite constituting the most abundant product of influenza infection, the role that the 'noninfectious' particle fraction plays in the biology of the virus has largely been ignored. This review shines a light on this oft-ignored population by highlighting studies, both old and new, that describe the unique biological activities of these particles, and discussing what this population can tell us about the biology of IAV evolution and disease. C1 NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Brooke, CB (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. EM brookecb@niaid.nih.gov FU Intramural Research Program of the NIH, NIAID FX The author is supported by the Intramural Research Program of the NIH, NIAID. The author has 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 103 TC 8 Z9 8 U1 0 U2 9 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0794 EI 1746-0808 J9 FUTURE VIROL JI Future Virol. PD JAN PY 2014 VL 9 IS 1 BP 41 EP 51 DI 10.2217/FVL.13.118 PG 11 WC Virology SC Virology GA AF9BD UT WOS:000335009100009 PM 25067941 ER PT J AU Kang, MG Won, EJ Choi, HW Kim, HR Choi, HJ Park, HR Shin, JH Suh, SP Ryang, DW Shin, MG AF Kang, Min-Gu Won, Eun-Jeong Choi, Hyun-Woo Kim, Hye-Ran Choi, Hyun-Jung Park, Hye-Ri Shin, Jong-Hee Suh, Soon-Pal Ryang, Dong-Wook Shin, Myung-Geun TI Serum Parathyroid Hormone Is a New Potential Risk Factor in Multiple Myeloma SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID STEM-CELL NICHE AB We hypothesized that serum PTH might be associated with various clinicopathological parameters in multiple myeloma (MM). So we investigated the implications of serum PTH in MM patients and the relationship with other risk factors of MM. A total of 115 patients who were newly diagnosed with MM were enrolled. Serum PTH level was 24.7 +/- 34.9 (ranged 0.0-284.1) pg/mL. Serum levels of IgG, IgM, FLC-lambda, albumin, and LDH were in positive correlation with serum PTH. Compared to non-high PTH (<68.3 pg/mL) group, the hazard ratio (HR) for overall survival was higher for group with high PTH level (>68.3 pg/mL) (HR, 1.710). Furthermore, the patient group with high PTH level showed inferior progression-free survival than non-high PTH group (P = 0.056). Interestingly, subgroup analysis showed that serum PTH level at diagnosis was associated with risk factors and clinical outcome in MM patients, especially in complete remission group, transplantation cases, ISS stage II cases, and cases without chromosome abnormality. In conclusion, this study showed that blood PTH level in MM at diagnosis was associated with risk factors and clinical outcome in MM patients. C1 [Kang, Min-Gu; Won, Eun-Jeong; Choi, Hyun-Woo; Choi, Hyun-Jung; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook; Shin, Myung-Geun] Chonnam Natl Univ, Sch Med, Dept Lab Med, Hwasun Gun 519809, Jeollanam Do, South Korea. [Kang, Min-Gu; Won, Eun-Jeong; Choi, Hyun-Woo; Choi, Hyun-Jung; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook; Shin, Myung-Geun] Chonnam Natl Univ, Hwasun Hosp, Hwasun Gun 519809, Jeollanam Do, South Korea. [Kim, Hye-Ran] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Park, Hye-Ri; Shin, Myung-Geun] Chonnam Natl Univ, Sch Med, Brain Korea Plus Project 21, Kwangju, South Korea. RP Shin, MG (reprint author), Chonnam Natl Univ, Sch Med, Dept Lab Med, 160 Ilsim Ri, Hwasun Gun 519809, Jeollanam Do, South Korea. EM mgshin@chonnam.ac.kr OI Choi, Hyun-Woo/0000-0002-9438-1603; Kang, Min-Gu/0000-0003-4946-8512 FU National Research Foundation of Korea (NRF) [2011-0015304]; NRF Basic Science Research Program [2010-0024326]; Leading Foreign Research Institute Recruitment Program through the NRF - Ministry of Education, Science and Technology (MEST) [2011-0030034]; National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea [2013-1320070] FX This study was supported by the National Research Foundation of Korea (NRF) (grant no. 2011-0015304), the NRF Basic Science Research Program (Grant 2010-0024326), the Leading Foreign Research Institute Recruitment Program (no. 2011-0030034) through the NRF funded by the Ministry of Education, Science and Technology (MEST), and a Grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (no. 2013-1320070). NR 13 TC 1 Z9 1 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 804182 DI 10.1155/2014/804182 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AI0ZJ UT WOS:000336579000001 ER PT J AU Gao, J Xu, HL Gao, S Zhang, W Tan, YT Rothman, N Purdue, M Gao, YT Zheng, W Shu, XO Xiang, YB AF Gao, Jing Xu, Hong-Li Gao, Shan Zhang, Wei Tan, Yu-Ting Rothman, Nat Purdue, Mark Gao, Yu-Tang Zheng, Wei Shu, Xiao-Ou Xiang, Yong-Bing TI Genetic polymorphism of NFKB1 and NFKBIA genes and liver cancer risk: a nested case-control study in Shanghai, China SO BMJ OPEN LA English DT Article DE Epidemiology ID NF-KAPPA-B; FUNCTIONAL INSERTION/DELETION POLYMORPHISM; COLORECTAL-CANCER; TRANSCRIPTION FACTOR; PROMOTER REGION; INCREASES SUSCEPTIBILITY; HEPATOCELLULAR-CARCINOMA; CHROMOSOMAL LOCALIZATION; OVARIAN-CANCER; WOMENS HEALTH AB Objectives Genetic variations of nuclear factor-B (NF-B) signalling pathway were found to be associated with inflammatory diseases and several malignancies. However, little is known about NF-B pathway gene polymorphisms and susceptibility of liver cancer. The aim of this study was to investigate whether genetic variants of NFKB1 and NFKBIA were associated with risk of liver cancer in a Chinese population. Design The study was designed as a nested case-control study within two prospective cohorts (the Shanghai Women's Health Study, SWHS, 1996-2000 and the Shanghai Men's Health Study, SMHS, 2002-2006). Settings This population-based study was conducted in urban Shanghai, China. Participants A total of 217 incident liver cancer cases diagnosed through 31 December 2009 and 427 healthy controls matched by sex, age at baseline (2years) and date (30days) of sample collection were included in the study. Primary and secondary outcome measures Genetic polymorphisms of NFKB1 and NFKBIA were determined blindly by TaqMan single-nucleotide polymorphism (SNP) genotyping assay. OR and its 95% CIs were estimated by an unconditional logistic regression model to measure the association between selected SNPs and the risk of liver cancer. Results After adjusted for potential confounding factors, rs28362491 ins/del or del/del genotypes were associated with higher risk of liver cancer with an adjusted OR 1.54 (95% CI 1.04 to 2.28). rs230496 AG and GG genotypes were also noted with higher risk of liver cancer with an adjusted OR 1.53 (95% CI 1.03 to 2.26). Haplotype analysis indicated that carriers of the NFKB1 GA and AA (rs230525-rs230530) haplotypes had higher risk of liver cancer under an additive model. No association was observed between NFKBIA variants and risk of live cancer. Conclusions Our results suggest that genetic variants of NFKB1 influence liver cancer susceptibility in Chinese population, although replication in other studies is needed. C1 [Gao, Jing; Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Canc Inst, State Key Lab Oncogene & Related Genes,Sch Med, Shanghai 200030, Peoples R China. [Gao, Jing; Xu, Hong-Li; Zhang, Wei; Tan, Yu-Ting; Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Shanghai Canc Inst, Renji Hosp, Dept Epidemiol,Sch Med, Shanghai 200030, Peoples R China. [Gao, Shan] Zhengzhou Univ, Dept Infect Management, Affiliated Hosp 1, Zhengzhou 450052, Peoples R China. [Rothman, Nat; Purdue, Mark] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Sch Med,Div Epidemiol,Dep Med, Nashville, TN 37212 USA. RP Xiang, YB (reprint author), Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Canc Inst, State Key Lab Oncogene & Related Genes,Sch Med, Shanghai 200030, Peoples R China. EM ybxiang@shsci.org FU State Key Project Specialised for Infectious Diseases of China [2008ZX10002-015, 2012ZX10002008-002]; US National Institutes of Health [R37 CA070867, R01 CA82729]; Shanghai Municipal Health Bureau [2008208] FX This work was supported by the funds of State Key Project Specialised for Infectious Diseases of China (No. 2008ZX10002-015, No. 2012ZX10002008-002 to Y-BX). The parent cohorts were supported by the grants (R37 CA070867 to W Zheng and R01 CA82729 to X-OS) from the US National Institutes of Health. Part of JG's effort on the study has been supported by research project of Shanghai Municipal Health Bureau (No. 2008208). NR 43 TC 8 Z9 8 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2014 VL 4 IS 2 DI 10.1136/bmjopen-2013-004427 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AF1FF UT WOS:000334459100069 ER PT J AU O'Brien, KS Blumberg, S Enanoria, WTA Ackley, S Sippl-Swezey, N Lietman, TM AF O'Brien, Kieran S. Blumberg, Seth Enanoria, Wayne T. A. Ackley, Sarah Sippl-Swezey, Nicolas Lietman, Thomas M. TI Antibiotic Use as a Tragedy of the Commons: A Cross-Sectional Survey SO COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE LA English DT Article ID ANTIMICROBIAL RESISTANCE; TRACHOMA CONTROL; MASS-DISTRIBUTION; YOUNG-CHILDREN; STREPTOCOCCUS-PNEUMONIAE; AZITHROMYCIN; PERCEPTIONS; KNOWLEDGE; ATTITUDES; RISK AB Background. Many believe antibiotic use results in a tragedy of the commons, since overuse may lead to antibiotic resistance and limiting use would benefit society. In contrast, mass antibiotic treatment programs are thought to result in community-wide benefits. A survey was conducted to learn the views of infectious disease experts on the individual- and societal-level consequences of antibiotic use. Methods. The survey instrument was designed to elicit opinions on antibiotic use and resistance. It was sent via SurveyMonkey to infectious disease professionals identified through literature searches. Descriptive statistics were used to analyze the data. Results. A total of 1,530 responses were received for a response rate of 9.9%. Nearly all participants believed antibiotic use could result in a tragedy of the commons, at least in certain circumstances (96.0%). Most participants did not believe mass antibiotic treatment programs could produce societal benefits in an antibiotic-free society (91.4%) or in the United States (94.2%), though more believed such programs would benefit antibiotic-free societies compared to the United States (P < 0.001). Conclusions. The experts surveyed believe that antibiotic use can result in a tragedy of the commons and do not believe that mass treatment programs benefit individuals or society. C1 [O'Brien, Kieran S.; Blumberg, Seth; Enanoria, Wayne T. A.; Ackley, Sarah; Sippl-Swezey, Nicolas; Lietman, Thomas M.] Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA. [Blumberg, Seth] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Lietman, Thomas M.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Lietman, Thomas M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA. RP Lietman, TM (reprint author), Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA. EM tom.lietman@ucsf.edu FU Bill and Melinda Gates Foundation [OPP1032340]; National Institutes of Health MIDAS program (NIH NIGMS) [1-U01-GM087728]; RAPIDD program of the Science and Technology Directorate at the Department of Homeland Security; Fogarty International Center of the National Institutes of Health FX The authors were supported by a Bill and Melinda Gates Foundation Global Health Grant (OPP1032340), the National Institutes of Health MIDAS program (Modeling Infectious Disease Agent Study, NIH NIGMS 1-U01-GM087728), the RAPIDD program of the Science and Technology Directorate at the Department of Homeland Security, and the Fogarty International Center of the National Institutes of Health. NR 37 TC 0 Z9 0 U1 1 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1748-670X EI 1748-6718 J9 COMPUT MATH METHOD M JI Comput. Math. Method Med. PY 2014 AR 837929 DI 10.1155/2014/837929 PG 8 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA AI0PA UT WOS:000336548500001 ER PT J AU Salles, FT Andrade, LR Tanda, S Grati, M Plona, KL Gagnon, LH Johnson, KR Kachar, B Berryman, MA AF Salles, Felipe T. Andrade, Leonardo R. Tanda, Soichi Grati, M'hamed Plona, Kathleen L. Gagnon, Leona H. Johnson, Kenneth R. Kachar, Bechara Berryman, Mark A. TI CLIC5 stabilizes membrane-actin filament linkages at the base of hair cell stereocilia in a molecular complex with radixin, taperin, and myosin VI SO CYTOSKELETON LA English DT Article DE PTPRQ; taperin; radixin; deafness; myosin VI (MYO6); ezrin-radixin-moesin (ERM); chloride intracellular channel 5 (CLIC5); cytoskeleton; hair cell; stereocilia ID NONSYNDROMIC HEARING-LOSS; SNELLS-WALTZER MICE; MOUSE INNER-EAR; TIP-LINK; SCAFFOLDING PROTEIN; CHLORIDE CHANNEL; EPITHELIAL-CELLS; GOLGI-APPARATUS; RAPID TURNOVER; HIGH-FREQUENCY AB Chloride intracellular channel 5 protein (CLIC5) was originally isolated from microvilli in complex with actin binding proteins including ezrin, a member of the Ezrin-Radixin-Moesin (ERM) family of membrane-cytoskeletal linkers. CLIC5 concentrates at the base of hair cell stereocilia and is required for normal hearing and balance in mice, but its functional significance is poorly understood. This study investigated the role of CLIC5 in postnatal development and maintenance of hair bundles. Confocal and scanning electron microscopy of CLIC5-deficient jitterbug (jbg) mice revealed progressive fusion of stereocilia as early as postnatal day 10. Radixin (RDX), protein tyrosine phosphatase receptor Q (PTPRQ), and taperin (TPRN), deafness-associated proteins that also concentrate at the base of stereocilia, were mislocalized in fused stereocilia of jbg mice. TPRQ and RDX were dispersed even prior to stereocilia fusion. Biochemical assays showed interaction of CLIC5 with ERM proteins, TPRN, and possibly myosin VI (MYO6). In addition, CLIC5 and RDX failed to localize normally in fused stereocilia of MYO6 mutant mice. Based on these findings, we propose a model in which these proteins work together as a complex to stabilize linkages between the plasma membrane and subjacent actin cytoskeleton at the base of stereocilia. Published 2013-Wiley Periodicals, Inc. This article is a US government work and, as such, is in the public domain in the United States of America. C1 [Salles, Felipe T.; Andrade, Leonardo R.; Grati, M'hamed; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, NIH, Bethesda, MD USA. [Tanda, Soichi; Plona, Kathleen L.] Ohio Univ, Dept Biol Sci, Athens, OH 45701 USA. [Tanda, Soichi; Berryman, Mark A.] Ohio Univ, Interdisciplinary Program Mol & Cellular Biol, Athens, OH 45701 USA. [Gagnon, Leona H.; Johnson, Kenneth R.] Jackson Lab, Bar Harbor, ME 04609 USA. [Berryman, Mark A.] Ohio Univ, Dept Biomed Sci, Athens, OH 45701 USA. RP Berryman, MA (reprint author), Ohio Univ, Dept Biomed Sci, Athens, OH 45701 USA. EM berryman@ohio.edu RI Andrade, Leonardo/C-9554-2011 OI Andrade, Leonardo/0000-0002-0004-5677 FU Ohio University Heritage College of Osteopathic Medicine; National Institutes of Health [DC004301] FX The authors thank Kira Slepchenko for technical assistance, Danette Pratt for assistance with graphic art, Dr. Anthony Bretscher (Cornell University) for generous gifts of antibodies, Dr. James Bartles (Northwestern University) for LLC-PK1-CL4 cells, and Dr. Anthony Peng and Dr. Janet Duerr for helpful comments on the manuscript. M.A.B. and S.T. received financial support from Ohio University Heritage College of Osteopathic Medicine. K.R.J. and L.H.G. were supported by National Institutes of Health grant DC004301. The authors declare no conflict of interest. NR 85 TC 12 Z9 12 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1949-3584 EI 1949-3592 J9 CYTOSKELETON JI Cytoskeleton PD JAN PY 2014 VL 71 IS 1 BP 61 EP 78 DI 10.1002/cm.21159 PG 18 WC Cell Biology SC Cell Biology GA AD8QC UT WOS:000333529700005 PM 24285636 ER PT J AU Jarcho, JM Fox, NA Pine, DS Leibenluft, E Shechner, T Degnan, KA Perez-Edgar, K Ernst, M AF Jarcho, Johanna M. Fox, Nathan A. Pine, Daniel S. Leibenluft, Ellen Shechner, Tomer Degnan, Kathryn A. Perez-Edgar, Koraly Ernst, Monique TI ENDURING INFLUENCE OF EARLY TEMPERAMENT ON NEURAL MECHANISMS MEDIATING ATTENTION-EMOTION CONFLICT IN ADULTS SO DEPRESSION AND ANXIETY LA English DT Article DE personality; magnetic resonance imaging; emotions; attention; risk factor; anxiety ID CHILDHOOD BEHAVIORAL-INHIBITION; ANTERIOR CINGULATE CORTEX; SOCIAL ANXIETY DISORDER; WORKING-MEMORY TASK; COGNITIVE CONTROL; PSYCHOMETRIC PROPERTIES; GENERALIZED ANXIETY; IMPLICIT REGULATION; CHILDREN; THREAT AB BackgroundBehavioral inhibition, a temperament identified in early childhood, is often associated with dysregulated attention and affective processing, particularly in response to threat. Longitudinal studies find that the manifestation of perturbed attention and affective processing often dissipates with age. Yet, childhood behavioral inhibition continues to predict perturbed brain function into adulthood. This suggests that adults with childhood behavioral inhibition may engage compensatory processes to effectively regulate emotion-related attention. However, it is unknown whether perturbations in brain function reflect compensation for attention bias to emotional stimuli generally, or to threatening contexts more specifically. The present study tests these possibilities. MethodsAdults with and without a history of stable childhood behavioral inhibition completed an attention-control task in the context of threatening and nonthreatening stimuli while undergoing functional magnetic resonance imaging. Participants were asked to identify the gender of fearful (threatening) and happy (nonthreatening) faces, while ignoring both the face emotion and overlaid congruent (low attention control, LAC) or incongruent (high attention control, HAC) gender words. ResultsWhen fearful faces were present, adults with stable childhood behavioral inhibition exhibited more activity in striatum, cingulate, and dorsolateral prefrontal cortex for HAC trials compared with LAC trials, relative to those without behavioral inhibition. When happy faces were present, the opposite activation pattern emerged. No group differences in behavior were observed. ConclusionsAmong adults, stable childhood behavioral inhibition predicts neural, but not behavioral, responding when attention control is engaged in discrete emotional contexts. This suggests a mechanism by which adults may compensate for the behavioral manifestation of threat-based attention biases. C1 [Jarcho, Johanna M.; Pine, Daniel S.; Shechner, Tomer; Ernst, Monique] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. [Fox, Nathan A.; Degnan, Kathryn A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA. [Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Bethesda, MD 20892 USA. [Perez-Edgar, Koraly] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. [Perez-Edgar, Koraly] Penn State Univ, Ctr Child Study, University Pk, PA 16802 USA. RP Jarcho, JM (reprint author), NIMH, Sect Dev & Affect Neurosci, NIH, 9000 Rockville Pike,Bldg 15K, Bethesda, MD 20892 USA. EM johanna.jarcho@nih.gov OI Jarcho, Johanna/0000-0001-9075-6968; Perez-Edgar, Koraly/0000-0003-4051-9563 FU National Institute of Mental Health [NAF: R01 MH074454]; National Institute of Child Health and Development Grant [NAF: 5R37 HD 017899-20] FX Contract grant sponsor: National Institute of Mental Health Grant; Contract grant number: NAF: R01 MH074454; Contract grant sponsor: National Institute of Child Health and Development Grant; Contract grant number: NAF: 5R37 HD 017899-20. NR 51 TC 12 Z9 12 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JAN PY 2014 VL 31 IS 1 BP 53 EP 62 DI 10.1002/da.22140 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA AF2EY UT WOS:000334526600007 PM 23861165 ER PT J AU Grant, RW Clark, NG Desouza, CV Funnell, MM Goldfine, AB Laffel, L Marks, JB McCall, AL McWilliams, JR Pop-Busui, R Rasouli, N Rodriguez, H Simmons, DL Stankaitis, J Urbanski, P Fradkin, J Chiang, J Dunbar, S AF Grant, Richard W. Clark, Nathaniel G. Desouza, Cyrus V. Funnell, Martha M. Goldfine, Allison B. Laffel, Lori Marks, Jennifer B. McCall, Anthony L. McWilliams, Janis R. Pop-Busui, Rodica Rasouli, Neda Rodriguez, Henry Simmons, Debra L. Stankaitis, Joseph Urbanski, Patti Fradkin, Judith Chiang, Jane Dunbar, Stephanie TI Professional Practice Committee for the 2014 Clinical Practice Recommendations SO DIABETES CARE LA English DT Article C1 [Grant, Richard W.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Clark, Nathaniel G.] Jordan Hosp, Plymouth, MA USA. [Desouza, Cyrus V.] Univ Nebraska Med Ctr, Omaha, NE USA. [Desouza, Cyrus V.] Omaha VA Med Ctr, Omaha, NE USA. [Funnell, Martha M.; Pop-Busui, Rodica] Univ Michigan, Ann Arbor, MI 48109 USA. [Goldfine, Allison B.; Laffel, Lori] Joslin Diabet Ctr, Boston, MA 02215 USA. [Laffel, Lori] Harvard Univ, Sch Med, Boston, MA USA. [Marks, Jennifer B.] Miami VA, Miami, FL USA. [Marks, Jennifer B.] Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA. [McCall, Anthony L.] Univ Virginia, Charlottesville, VA USA. [Rasouli, Neda] Univ Colorado, Denver, CO 80202 USA. [Rasouli, Neda] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Rodriguez, Henry] Univ S Florida, Tampa, FL USA. [Simmons, Debra L.] Univ Utah, VA Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. [Stankaitis, Joseph] Monroe Plan Med Care, Pittsford, NY USA. [Urbanski, Patti] Pbu consulting LLC, Cloquet, MN USA. [Fradkin, Judith] NIDDK, Bethesda, MD 20892 USA. [Chiang, Jane; Dunbar, Stephanie] ADA, Alexandria, VA USA. RP Grant, RW (reprint author), Kaiser Permanente, Div Res, Oakland, CA 94612 USA. FU AHRQ; NIDDK; Novo Nordisk; Asahi Kasei Pharma America; NHLBI; ADA; Daiichi Sankyo; Merck; Bayer; NIH; NICHD; T1D Exchange; Lilly; T1D Exchange Clinic Registry; Sanofi; Eli Lilly; LaunchPad; Bristol-Myers Squibb; Pfizer; Novartis; TrialNet; Helmsley Trust; New York Health Foundation; CDC; Takeda; Halozyme Therapeutics; Bristol-Myers Squibb/AstraZeneca Diabetes; Hygeia Inc.; Boehringer Ingelheim; GlaxoSmithKline; Johnson Johnson; Animas/LifeScan; Intuity Medical; Bayer Diagnostics; Oshadi Administrative Devices; Menarini; JDRF (International Advisory Board); LifeScan; Roche; Amgen; Janssen Pharmaceuticals, Inc.; AstraZeneca; Roche Diagnostics; TPG National Payor Roundtable; Celgene; Gilead; Medtronic; YourEncore Network FX Richard W. Grant, MD, MPH (Chair); AHRQ#, NIDDK#; Cyrus V. Desouza, MBBS; NIDDK#, Novo Nordisk#, Asahi Kasei Pharma America#; Allison B. Goldfine, MD; NIDDK#, NHLBI#, ADA#, Daiichi Sankyo#, Merck (site investigator); Lori Laffel, MD, MPH; Bayer#, NIH#, NIDDK#, NICHD#, T1D Exchange; B. Marks, MD; Lilly#, NIH#, NIDDK#, T1D Exchange Clinic Registry#; Anthony L. McCall, MD, PhD; Sanofi#, Eli Lilly#, NIDDK#, LaunchPad (UVA internal grant); Rodica Pop-Busui, MD, PhD; Bristol-Myers Squibb#, NIDDK#, NHLBI#; Neda Rasouli, MD; Novo Nordisk#, Bristol-Myers Squibb#, Merck#, NIDDK#, Pfizer#; Henry Rodriguez, MD; NIH#, Bristol-Myers Squibb#, Daiichi Sankyo#, Novartis#, Novo Nordisk#, TrialNet, Helmsley Trust; Joseph Stankaitis, MD, MPH; New York Health Foundation#, CDC#; C.V.D.; Novo Nordisk, Takeda; M.M.F.; Eli Lilly, Halozyme Therapeutics, Bristol-Myers Squibb/AstraZeneca Diabetes, Hygeia Inc., Boehringer Ingelheim, GlaxoSmithKline, Johnson & Johnson, Animas/LifeScan, Intuity Medical, Novo Nordisk, Bayer Diagnostics; L.L.; Oshadi Administrative Devices, Eli Lilly, Menarini, Johnson & Johnson, JDRF (International Advisory Board), Bristol-Myers Squibb, LifeScan, Sanofi, Roche, Novo Nordisk, Boehringer Ingelheim; J.B.M.; Amgen; R.P.-B.; T1D Exchange; Janssen Pharmaceuticals, Inc.; AstraZeneca; H.R.; Roche Diagnostics; J.S.; TPG National Payor Roundtable; Amgen; Celgene; Gilead; Janssen Pharmaceuticals, Inc.; P.U.; Eli Lilly; Medtronic; YourEncore Network; Janssen Pharmaceuticals, Inc. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2014 VL 37 SU 1 BP S154 EP S155 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI0EG UT WOS:000336518400014 ER PT J AU Kidder, BL Hu, GQ Zhao, K AF Kidder, Benjamin L. Hu, Gangqing Zhao, Keji TI KDM5B focuses H3K4 methylation near promoters and enhancers during embryonic stem cell self-renewal and differentiation SO GENOME BIOLOGY LA English DT Article ID TRANSCRIPTIONAL REGULATORY CIRCUITRY; HUMAN GENOME; GENE-EXPRESSION; ES CELLS; EPIGENETIC REGULATION; HISTONE METHYLATION; ACTIVE GENES; TARGET GENES; DEMETHYLASE; LSD1 AB Background: Pluripotency of embryonic stem (ES) cells is controlled in part by chromatin-modifying factors that regulate histone H3 lysine 4 (H3K4) methylation. However, it remains unclear how H3K4 demethylation contributes to ES cell function. Results: Here, we show that KDM5B, which demethylates lysine 4 of histone H3, co-localizes with H3K4me3 near promoters and enhancers of active genes in ES cells; its depletion leads to spreading of H3K4 methylation into gene bodies and enhancer shores, indicating that KDM5B functions to focus H3K4 methylation at promoters and enhancers. Spreading of H3K4 methylation to gene bodies and enhancer shores is linked to defects in gene expression programs and enhancer activity, respectively, during self-renewal and differentiation of KDM5B-depleted ES cells. KDM5B critically regulates H3K4 methylation at bivalent genes during differentiation in the absence of LIF or Oct4. We also show that KDM5B and LSD1, another H3K4 demethylase, co-regulate H3K4 methylation at active promoters but they retain distinct roles in demethylating gene body regions and bivalent genes. Conclusions: Our results provide global and functional insight into the role of KDM5B in regulating H3K4 methylation marks near promoters, gene bodies, and enhancers in ES cells and during differentiation. C1 [Kidder, Benjamin L.; Hu, Gangqing; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Kidder, BL (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM benjamin.kidder@nih.gov; zhaok@nhlbi.nih.gov RI HU, GANGQING/K-5849-2012 FU Division of Intramural Research of the National Heart, Lung and Blood Institute FX This work was supported by the Division of Intramural Research of the National Heart, Lung and Blood Institute. The DNA Sequencing Core facility of NHLBI assisted with this work. NR 62 TC 24 Z9 24 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 2 AR R32 DI 10.1186/gb-2014-15-2-r32 PG 19 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AH6QU UT WOS:000336256600015 PM 24495580 ER PT J AU Rogozin, IB Managadze, D Shabalina, SA Koonin, EV AF Rogozin, Igor B. Managadze, David Shabalina, Svetlana A. Koonin, Eugene V. TI Gene Family Level Comparative Analysis of Gene Expression in Mammals Validates the Ortholog Conjecture SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE duplicated genes; selection; neutral evolution; rebalancing dosage effect model; duplication-degeneration-complementation model; neofunctionalization model; subfunctionalization model ID DUPLICATED GENES; RNA-SEQ; EVOLUTION; DUPLICABILITY; PROTEINS; MOUSE; YEAST; TRANSCRIPTOMES; COMPLEMENTARY; DIVERGENCE AB The ortholog conjecture (OC), which is central to functional annotation of genomes, posits that orthologous genes are functionally more similar than paralogous genes at the same level of sequence divergence. However, a recent study challenged the OC by reporting a greater functional similarity, in terms of Gene Ontology (GO) annotations and expression profiles, among within-species paralogs compared with orthologs. These findings were taken to indicate that functional similarity of homologous genes is primarily determined by the cellular context of the genes, rather than evolutionary history. However, several subsequent studies suggest that GO annotations and microarray data could artificially inflate functional similarity between paralogs from the same organism. We sought to test the OC using approaches distinct from those used in previous studies. Analysis of a large RNAseq data set from multiple human and mouse tissues shows that expression similarity (correlations coefficients, rank's, or Z-scores) between orthologs is substantially greater than that for between-species paralogs with the same sequence divergence, in agreement with the OC and the results of recent detailed analyses. These findings are further corroborated by a fine-grain analysis in which expression profiles of orthologs and paralogs were compared separately for individual gene families. Expression profiles of within-species paralogs are more strongly correlated than profiles of orthologs but it is shown that this is caused by high background noise, that is, correlation between profiles of unrelated genes in the same organism. Z-scores and rank scores show a nonmonotonic dependence of expression profile similarity on sequence divergence. This complexity of gene expression evolution after duplication might be at least partially caused by selection for protein dosage rebalancing following gene duplication. C1 [Rogozin, Igor B.; Managadze, David; Shabalina, Svetlana A.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM koonin@ncbi.nlm.nih.gov FU National Library of Medicine at National Institutes of Health (US Department Health and Human Services) FX We thank Koonin group members for useful discussions and Jean and Danielle Thierry-Mieg for helpful advice on RNAseq data analysis. This work was supported by the Intramural Research Program of the National Library of Medicine at National Institutes of Health (US Department Health and Human Services). NR 47 TC 6 Z9 6 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2014 VL 6 IS 4 BP 754 EP 762 DI 10.1093/gbe/evu051 PG 9 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA AH4EW UT WOS:000336080700002 PM 24610837 ER PT J AU Sokolov, M Neumann, R AF Sokolov, Mykyta Neumann, Ronald TI Effects of Low Doses of Ionizing Radiation Exposures on Stress-Responsive Gene Expression in Human Embryonic Stem Cells SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE gene expression changes; low dose exposures; ionizing radiation; human embryonic stem cells ID HUMAN LYMPHOBLASTOID-CELLS; NORMAL HUMAN FIBROBLASTS; NF-KAPPA-B; POLO-LIKE KINASE-3; DNA-DAMAGE; CYCLE ARREST; P53 PATHWAY; HUMAN SKIN; IN-VIVO; MICROARRAY ANALYSIS AB There is a great deal of uncertainty on how low (<= 0.1 Gy) doses of ionizing radiation (IR) affect human cells, partly due to a lack of suitable experimental model systems for such studies. The uncertainties arising from low-dose IR human data undermine practical societal needs to predict health risks emerging from diagnostic medical tests' radiation, natural background radiation, and environmental radiological accidents. To eliminate a variability associated with remarkable differences in radioresponses of hundreds of differentiated cell types, we established a novel, human embryonic stem cell (hESC)-based model to examine the radiobiological effects in human cells. Our aim is to comprehensively elucidate the gene expression changes in a panel of various hESC lines following low IR doses of 0.01; 0.05; 0.1 Gy; and, as a reference, relatively high dose of 1 Gy of IR. Here, we examined the dynamics of transcriptional changes of well-established IR-responsive set of genes, including CDKN1A, GADD45A, etc. at 2 and 16 h post-IR, representing "early" and "late" radioresponses of hESCs. Our findings suggest the temporal- and hESC line-dependence of stress gene radioresponses with no statistically significant evidence for a linear dose-response relationship within the lowest doses of IR exposures. C1 [Sokolov, Mykyta; Neumann, Ronald] NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Sokolov, M (reprint author), NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM sokolovm@mail.nih.gov; rneumann@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, Clinical Center FX We are grateful to Van Nguyen for her assistance with the cell culture, and we thank William Degraff for his invaluable help with cell culture irradiation. This research was supported by the Intramural Research Program of the National Institutes of Health, Clinical Center. NR 83 TC 8 Z9 8 U1 0 U2 7 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD JAN PY 2014 VL 15 IS 1 BP 588 EP 604 DI 10.3390/ijms15010588 PG 17 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA AG9YM UT WOS:000335776100034 PM 24398983 ER PT J AU Mirochnick, M Taha, T Kreitchmann, R Nielsen-Saines, K Kumwenda, N Joao, E Pinto, J Santos, B Parsons, T Kearney, B Emel, L Herron, C Richardson, P Hudelson, SE Eshleman, SH George, K Fowler, MG Sato, P Mofenson, L AF Mirochnick, Mark Taha, Taha Kreitchmann, Regis Nielsen-Saines, Karin Kumwenda, Newton Joao, Esau Pinto, Jorge Santos, Breno Parsons, Teresa Kearney, Brian Emel, Lynda Herron, Casey Richardson, Paul Hudelson, Sarah E. Eshleman, Susan H. George, Kathleen Fowler, Mary G. Sato, Paul Mofenson, Lynne CA HPTN 057 Protocol Team TI Pharmacokinetics and Safety of Tenofovir in HIV-Infected Women During Labor and Their Infants During the First Week of Life SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE neonate; pharmacokinetics; tenofovir ID IMMUNODEFICIENCY VIRUS-INFECTION; HIV-1-INFECTED PREGNANT-WOMEN; TO-CHILD TRANSMISSION; DISOPROXIL FUMARATE; RHESUS MACAQUES; ANRS 12109; EMTRICITABINE; PREVENTION; PHARMACOLOGY; PROPHYLAXIS AB Background: Data describing the pharmacokinetics and safety of tenofovir in neonates are lacking. Methods: The HIV Prevention Trials Network 057 protocol was a phase 1, open-label study of the pharmacokinetics and safety of tenofovir disoproxil fumarate (TDF) in HIV-infected women during labor and their infants during the first week of life with 4 dosing cohorts: maternal 600 mg doses/no infant dosing; no maternal dosing/infant 4 mg/kg doses on days 0, 3, and 5; maternal 900 mg doses/infant 6 mg/kg doses on days 0, 3, and 5; maternal 600 mg doses/infant 6 mg/kg daily for 7 doses. Pharmacokinetic sampling was performed on cohort 1 and 3 mothers and all infants. Plasma, amniotic fluid, and breast milk tenofovir concentrations were determined by liquid chromatographic-tandem mass spectrometric assay. The pharmacokinetic target was for infant tenofovir concentration throughout the first week of life to exceed 50 ng/mL, the median trough tenofovir concentration in adults receiving standard chronic TDF dosing. Results: One hundred twenty-two mother-infant pairs from Malawi and Brazil were studied. Tenofovir exposure in mothers receiving 600 and 900 mg exceeded that in nonpregnant adults receiving standard 300 mg doses. Tenofovir elimination in the infants was equivalent to that in older children and adults, and trough tenofovir plasma concentrations exceeded 50 ng/mL in 74%-97% of infants receiving daily dosing. Conclusions: A TDF dosing regimen of 600 mg during labor and daily infant doses of 6 mg/kg maintains infant tenofovir plasma concentration above 50 ng/mL throughout the first week of life and should be used in the studies of TDF efficacy for HIV prevention of mother-to-child transmission and early infant treatment. C1 [Mirochnick, Mark] Boston Univ Sch Med, Dept Pediat, Boston, MA USA. [Taha, Taha; Kumwenda, Newton] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Kreitchmann, Regis] Irmandade Santa Casa Misericordia Porto Alegre, HIV AIDS Res Dept, Porto Alegre, RS, Brazil. [Nielsen-Saines, Karin] David Geffen UCLA Sch Med, Dept Pediat, Los Angeles, CA USA. [Kumwenda, Newton] Malawi Coll Med, Blantyre, Malawi. [Joao, Esau] Hosp Fed Servidores Estado, Dept Infect Dis, Rio De Janeiro, Brazil. [Pinto, Jorge] Univ Fed Minas Gerais, Dept Pediat, Sch Med, Belo Horizonte, MG, Brazil. [Santos, Breno] Hosp Nossa Senhora Conceicao, Serv Infectol, Porto Alegre, RS, Brazil. [Parsons, Teresa] Johns Hopkins Univ Sch Med, Div Clin Pharmacol, Dept Med, Baltimore, MD USA. [Kearney, Brian] Gilead Sci Inc, Foster City, CA 94404 USA. [Emel, Lynda; Herron, Casey] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA. [Richardson, Paul; Hudelson, Sarah E.; Eshleman, Susan H.; Fowler, Mary G.] Johns Hopkins Univ Sch Med, Dept Pathol, Baltimore, MD USA. [George, Kathleen] Family Hlth Int, Durham, NC USA. [Fowler, Mary G.] Makerere Univ Hopkins Univ Res Collaborat, Kampala, Uganda. [Sato, Paul] NIAID, NIH, Bethesda, MD 20892 USA. [Mofenson, Lynne] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD USA. RP Mirochnick, M (reprint author), Boston Med Ctr, 771 Albany St,Dowling 4N Room 4111, Boston, MA 02043 USA. EM markm@bu.edu OI Mofenson, Lynne/0000-0002-2818-9808 FU International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT); HIV Prevention Trials Network (HPTN); National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH) [AI068632]; Statistical and Data Analysis Center at Harvard School of Public Health under the NIAID [5 U01 AI41110, 1 U01 AI068616]; NICHD [N01-DK-9-001/HHSN267200800001C]; NIAID; NICHD; National Institute on Drug Abuse; NIMH; Office of AIDS Research of the National Institutes of Health, US Department of Health and Human Services [U01 AI046749] FX Supported by the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) and HIV Prevention Trials Network (HPTN). Overall support for IMPAACT was provided by the National Institute of Allergy and Infectious Diseases (NIAID) (U01 AI068632), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) (AI068632). Study was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the NIAID cooperative agreement 5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group and 1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the NIAID and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). The HPTN is sponsored by the NIAID, NICHD, National Institute on Drug Abuse, NIMH, and Office of AIDS Research of the National Institutes of Health, US Department of Health and Human Services under award U01 AI046749. NR 19 TC 18 Z9 19 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2014 VL 65 IS 1 BP 33 EP 41 DI 10.1097/QAI.0b013e3182a921eb PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AG8DY UT WOS:000335650200011 PM 23979002 ER PT J AU Adimora, AA Hughes, JP Wang, J Haley, DF Golin, CE Magnus, M Rompalo, A Justman, J del Rio, C El-Sadr, W Mannheimer, S Soto-Torres, L Hodder, SL AF Adimora, Adaora A. Hughes, James P. Wang, Jing Haley, Danielle F. Golin, Carol E. Magnus, Manya Rompalo, Anne Justman, Jessica del Rio, Carlos El-Sadr, Wafaa Mannheimer, Sharon Soto-Torres, Lydia Hodder, Sally L. CA HPTN 064 Protocol Team TI Characteristics of Multiple and Concurrent Partnerships Among Women At High Risk for HIV Infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE concurrent partnerships; HIV; perceived partner concurrency; sexual networks; indirect concurrency; epidemiology ID SEXUALLY-TRANSMITTED INFECTIONS; UNITED-STATES; AFRICAN-AMERICANS; SEX PARTNERS; TRANSMISSION; BEHAVIOR; NETWORKS; DYNAMICS; MEN AB Objectives: We examined parameters of sexual partnerships, including respondents' participation in concurrency, belief that their partner had concurrent partnerships (partners' concurrency), and partnership intervals, among the 2099 women in HIV Prevention Trials Network 064, a study of women at high risk for HIV infection, in 10 U.S. communities. Methods: We analyzed baseline survey responses about partnership dates to determine prevalence of participants' and partners' concurrency, intervals between partnerships, knowledge of whether recent partners had undergone HIV testing, and intercourse frequency during the preceding 6 months. Results: Prevalence of participants' and partners' concurrency was 40% and 36%, respectively; 24% respondents had both concurrent partnerships and nonmonogamous partners. Among women with >1 partner and no concurrent partnerships themselves, the median gap between partners was 1 month. Multiple episodes of unprotected vaginal intercourse with >= 2 of their most recent partners was reported by 60% of women who had both concurrent partnerships and nonmonogamous partners, 50% with only concurrent partners and no partners' concurrency, and 33% with only partners' concurrency versus 14% of women with neither type of concurrency (P < 0.0001). Women who had any involvement with concurrency were also more likely than women with no concurrency involvement to report lack of awareness of whether recent partners had undergone HIV testing (participants' concurrency 41%, partners' concurrency 40%, both participants' and partners' concurrency 48%, neither 17%; P < 0.0001). Conclusions: These network patterns and short gaps between partnerships may create substantial opportunities for HIV transmission in this sample of women at high risk for HIV infection. C1 [Adimora, Adaora A.; Golin, Carol E.] Univ North Carolina Sch Med, Div Infect Dis, Chapel Hill, NC USA. [Adimora, Adaora A.; Golin, Carol E.] Univ N Carolina, UNC Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Hughes, James P.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Hughes, James P.; Wang, Jing] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Haley, Danielle F.] FHI 360, Durham, NC USA. [Magnus, Manya] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. [Rompalo, Anne] Johns Hopkins Univ Sch Med, Baltimore, MD USA. [Justman, Jessica; El-Sadr, Wafaa] Columbia Univ, CAP Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [del Rio, Carlos] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [del Rio, Carlos] Emory Univ, Ctr AIDS Res, Atlanta, GA 30322 USA. [Mannheimer, Sharon] Columbia Univ Coll Phys & Surg, Harlem Hosp Ctr, New York, NY 10032 USA. [Soto-Torres, Lydia] NIAID, NIH, Bethesda, MD 20892 USA. [Hodder, Sally L.] Rutgers State Univ, Newark, NJ 07102 USA. RP Adimora, AA (reprint author), UNC Sch Med, Div Infect Dis, 130 Mason Farm Rd,CB 7030, Chapel Hill, NC 27516 USA. EM adimora@med.unc.edu RI del Rio, Carlos/B-3763-2012 OI del Rio, Carlos/0000-0002-0153-3517 FU National Institute of Allergy and Infectious Diseases; National Institute on Drug Abuse; National Institute of Mental Health [UM1 AI068619, U01-AI068613, UM1-AI068613]; National Institute of Child Health and Human Development [5 K24HD059358-02]; Centers for Innovative Research to Control AIDS, Mailman School of Public Health, Columbia University [5U1Al069466]; University of North Carolina Clinical Trials Unit [AI069423]; University of North Carolina Clinical Trials Research Center of the Clinical and Translational Science Award [RR 025747]; University of North Carolina Center for AIDS Research [AI050410]; Emory University HIV/AIDS Clinical Trials Unit [5UO1AI069418]; Center for AIDS Research [P30 AI050409]; Clinical and Translational Science Award [UL1 RR025008]; Terry Beirn Community Programs for Clinical Research on AIDS Clinical Trials Unit [5 UM1 AI069503-07]; Johns Hopkins Adult AIDS Clinical Trial Unit [AI069465]; Johns Hopkins Clinical and Translational Science Award [UL1 RR 25005] FX Supported by the National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, and National Institute of Mental Health (cooperative agreement no. UM1 AI068619, U01-AI068613, and UM1-AI068613); National Institute of Child Health and Human Development (5 K24HD059358-02); Centers for Innovative Research to Control AIDS, Mailman School of Public Health, Columbia University (5U1Al069466); University of North Carolina Clinical Trials Unit (AI069423); University of North Carolina Clinical Trials Research Center of the Clinical and Translational Science Award (RR 025747); University of North Carolina Center for AIDS Research (AI050410); Emory University HIV/AIDS Clinical Trials Unit (5UO1AI069418), Center for AIDS Research (P30 AI050409), and Clinical and Translational Science Award (UL1 RR025008); The Terry Beirn Community Programs for Clinical Research on AIDS Clinical Trials Unit(5 UM1 AI069503-07); and The Johns Hopkins Adult AIDS Clinical Trial Unit (AI069465) and The Johns Hopkins Clinical and Translational Science Award (UL1 RR 25005). NR 30 TC 8 Z9 8 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2014 VL 65 IS 1 BP 99 EP 106 DI 10.1097/QAI.0b013e3182a9c22a PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AG8DY UT WOS:000335650200021 PM 24056163 ER PT J AU Avila, D Althoff, KN Mugglin, C Wools-Kaloustian, K Koller, M Dabis, F Nash, D Gsponer, T Sungkanuparph, S McGowan, C May, M Cooper, D Chimbetete, C Wolff, M Collier, A McManus, H Davies, MA Costagliola, D Crabtree-Ramirez, B Chaiwarith, R Cescon, A Cornell, M Diero, L Phanuphak, P Sawadogo, A Ehmer, J Eholie, SP Li, PCK Fox, MP Gandhi, NR Gonzalez, E Lee, CKC Hoffmann, CJ Kambugu, A Keiser, O Ditangco, R Prozesky, H Lampe, F Kumarasamy, N Kitahata, M Lugina, E Lyamuya, R Vonthanak, S Fink, V Monforte, AD Luz, PM Chen, YMA Minga, A Casabona, J Mwango, A Choi, JY Newell, ML Bukusi, EA Ngonyani, K Merati, TP Otieno, J Bosco, MB Phiri, S Ng, OT Anastos, K Rockstroh, J Santos, I Oka, S Somi, G Stephan, C Teira, R Wabwire, D Wandeler, G Boulle, A Reiss, P Wood, R Chi, BH Williams, C Sterne, JA Egger, M AF Avila, Dorita Althoff, Keri N. Mugglin, Catrina Wools-Kaloustian, Kara Koller, Manuel Dabis, Franois Nash, Denis Gsponer, Thomas Sungkanuparph, Somnuek McGowan, Catherine May, Margaret Cooper, David Chimbetete, Cleophas Wolff, Marcelo Collier, Ann McManus, Hamish Davies, Mary-Ann Costagliola, Dominique Crabtree-Ramirez, Brenda Chaiwarith, Romanee Cescon, Angela Cornell, Morna Diero, Lameck Phanuphak, Praphan Sawadogo, Adrien Ehmer, Jochen Eholie, Serge P. Li, Patrick C. K. Fox, Matthew P. Gandhi, Neel R. Gonzalez, Elsa Lee, Christopher K. C. Hoffmann, Christopher J. Kambugu, Andrew Keiser, Olivia Ditangco, Rossana Prozesky, Hans Lampe, Fiona Kumarasamy, Nagalingeswaran Kitahata, Mari Lugina, Emmanuel Lyamuya, Rita Vonthanak, Saphonn Fink, Valeria Monforte, Antonella d'Arminio Luz, Paula Mendes Chen, Yi-Ming A. Minga, Albert Casabona, Jordi Mwango, Albert Choi, Jun Y. Newell, Marie-Louise Bukusi, Elizabeth A. Ngonyani, Kapella Merati, Tuti P. Otieno, Juliana Bosco, Mwebesa B. Phiri, Sam Ng, Oon T. Anastos, Kathryn Rockstroh, Juergen Santos, Ignacio Oka, Shinichi Somi, Geoffrey Stephan, Christoph Teira, Ramon Wabwire, Deo Wandeler, Gilles Boulle, Andrew Reiss, Peter Wood, Robin Chi, Benjamin H. Williams, Carolyn Sterne, Jonathan A. Egger, Matthias CA IeDEA ART Cohort Collaborations TI Immunodeficiency at the Start of Combination Antiretroviral Therapy in Low-, Middle-, and High-Income Countries SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE sub-Saharan Africa; antiretroviral therapy; North America; CD4 cell count; Central and South America; Asia/Pacific; Europe; Carribean ID SUB-SAHARAN AFRICA; INTERNATIONAL EPIDEMIOLOGIC DATABASES; EVALUATE AIDS IEDEA; CD4(+) CELL COUNT; COLLABORATIVE ANALYSIS; COHORT PROFILE; HIV-1-INFECTED PATIENTS; BASE-LINE; HIV; INFECTION AB Objective: To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries. Methods: Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed. Results: In total, 379,865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/mu L between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/mu L (76% increase), 88 to 135 cells/mu L (53%), and 209 to 274 cells/mu L (31%). In 2009, compared with LIC, median counts were 13 cells/mu L [95% confidence interval (CI): -56 to +30] lower in LMIC, 22 cells/mu L (-62 to +18) lower in UMIC, and 112 cells/mu L (+75 to +149) higher in HIC. They were 23 cells/mu L (95% CI: +18 to +28 cells/mu L) higher in women than men. Median counts were 88 cells/mu L (95% CI: +35 to +141 cells/mu L) higher in countries with an estimated national cART coverage >80%, compared with countries with Conclusions: Median CD4 cell counts at the start of cART increased 2000-2009 but remained below 200 cells/mu L in LIC and MIC and below 300 cells/mu L in HIC. Earlier start of cART will require substantial efforts and resources globally. C1 [Avila, Dorita; Mugglin, Catrina; Koller, Manuel; Gsponer, Thomas; Keiser, Olivia; Egger, Matthias] Univ Bern, Inst Social & Prevent Med, CH-3012 Bern, Switzerland. [Althoff, Keri N.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Wools-Kaloustian, Kara] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Dabis, Franois] Univ Bordeaux Segalen, ISPED, Bordeaux, France. [Nash, Denis] CUNY, Sch Publ Hlth, New York, NY 10021 USA. [Sungkanuparph, Somnuek] Mahidol Univ, Ramathibodi Hosp, Fac Med, Bangkok 10400, Thailand. [McGowan, Catherine] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [May, Margaret] Univ Bristol, Sch Social & Community Med, Bristol BS8 1TH, Avon, England. [Cooper, David; McManus, Hamish; Sterne, Jonathan A.] Univ New S Wales, Kirby Inst, Sydney, NSW, Australia. [Chimbetete, Cleophas] Newlands Clin, Harare, Zimbabwe. [Wolff, Marcelo] Univ Chile, Fdn Arriaran, Santiago, Chile. [Collier, Ann; Kitahata, Mari] Univ Washington, Sch Med Ctr, Seattle, WA 98195 USA. [Davies, Mary-Ann; Cornell, Morna; Boulle, Andrew; Egger, Matthias] Univ Cape Town, Ctr Infect Dis Epidemiol & Res, ZA-7700 Rondebosch, South Africa. [Davies, Mary-Ann; Cornell, Morna; Boulle, Andrew; Egger, Matthias] Univ Cape Town, Sch Publ Hlth & Family Med, Div Epidemiol & Biostat, ZA-7700 Rondebosch, South Africa. [Costagliola, Dominique] Univ Paris 06, UMR S 943, Paris, France. [Crabtree-Ramirez, Brenda] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico. [Chaiwarith, Romanee] Res Inst Hlth Sci, Chiang Mai, Thailand. [Cescon, Angela] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Diero, Lameck] Moi Univ, Sch Med, Coll Hlth Sci, Acad Model Providing Access Hlth Care AMPATH, Eldoret, Kenya. [Phanuphak, Praphan] HIV NAT Thai Red Cross AIDS Res Ctr, Bangkok, Thailand. [Sawadogo, Adrien] CHU Souro Sanou, Bobo Dioulasso, Burkina Faso. [Ehmer, Jochen] SolidarMed African HIV Prevent & Treatment Progra, Luzern, Switzerland. [Eholie, Serge P.] CHU Treichville, SMIT, Abidjan, Cote Ivoire. [Li, Patrick C. K.] Queen Elizabeth Hosp, Hong Kong, Hong Kong, Peoples R China. [Fox, Matthew P.] Boston Univ, Ctr Global Hlth & Dev, Boston, MA 02215 USA. [Fox, Matthew P.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Fox, Matthew P.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Fox, Matthew P.] Univ Witwatersrand, Hlth Econ & Epidemiol Res Off, Johannesburg, South Africa. [Gandhi, Neel R.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. [Gandhi, Neel R.] Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA. [Gandhi, Neel R.] Emory Univ, Rollins Sch Publ Hlth, Dept Infect Dis, Atlanta, GA 30322 USA. [Gonzalez, Elsa] Univ Peruana Cayetano Heredia, Inst Med Trop Alexander von Humboldt, Lima, Peru. [Lee, Christopher K. C.] Hosp Sungai Buloh, Sungai Buloh, Malaysia. [Hoffmann, Christopher J.] Aurum Inst, Johannesburg, South Africa. [Hoffmann, Christopher J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Kambugu, Andrew] Infect Dis Inst, Kampala, Uganda. [Ditangco, Rossana] Res Inst Trop Med, Manila, Philippines. [Prozesky, Hans] Univ Stellenbosch, Div Infect Dis, Cape Town, South Africa. [Prozesky, Hans] Tygerberg Hosp, Cape Town, South Africa. [Lampe, Fiona] UCL, Res Dept Infect & Populat Hlth, London WC1E 6BT, England. [Kumarasamy, Nagalingeswaran] YRG Ctr AIDS Res & Educ, Chennai, Tamil Nadu, India. [Lugina, Emmanuel] Ocean Rd Canc Inst, Dar Es Salaam, Tanzania. [Lyamuya, Rita] Morogoro Reg Hosp, Morogoro, Tanzania. [Vonthanak, Saphonn] Natl Ctr HIV AIDS Dermatol & STDs, Phnom Penh, Cambodia. [Fink, Valeria] Fdn Huesped, Buenos Aires, DF, Argentina. [Monforte, Antonella d'Arminio] Univ Milan, San Paolo Hosp, Clin Infect Dis & Trop Med, I-20122 Milan, Italy. [Luz, Paula Mendes] Fundacao Oswaldo Cruz, Inst Pesquisa Clin Evandro Chagas, Rio De Janeiro, Brazil. [Chen, Yi-Ming A.] Taipei Vet Gen Hosp, Taipei, Taiwan. [Chen, Yi-Ming A.] Natl Yang Ming Univ, AIDS Prevent & Res Ctr, Taipei 112, Taiwan. [Minga, Albert] Ctr Med Suivi de Donneurs Sang CNTS PRIMO CI, Abidjan, Cote Ivoire. [Casabona, Jordi] Ctr Estudis Epidemiol ITS VIH SIDA Catalunya, Badalona, Spain. [Casabona, Jordi] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain. [Mwango, Albert] Zambian Minist Hlth, Lusaka, Zambia. [Choi, Jun Y.] Yonsei Univ, Coll Med, Dept Internal Med, Div Infect Dis, Seoul, South Korea. [Newell, Marie-Louise] Univ KwaZulu Natal, Africa Ctr Hlth & Populat Studies, Mtubatuba, South Africa. [Bukusi, Elizabeth A.] Family AIDS Care & Educ Serv FACES, Kisumu, Kenya. [Ngonyani, Kapella] Tumbi Reg Hosp, Kibaha, Tanzania. [Merati, Tuti P.] Udayana Univ, Fac Med, Bali, Indonesia. [Merati, Tuti P.] Sanglah Hosp, Bali, Indonesia. [Otieno, Juliana] MTCT Plus, Nyanza Prov Hosp, Kisumu, Kenya. [Bosco, Mwebesa B.] Mbarara Univ Sci & Technol, ISS Clin, Mbarara, Uganda. [Phiri, Sam] Lighthouse Trust, Lilongwe, Malawi. [Ng, Oon T.] Tan Tock Seng Hosp, Singapore, Singapore. [Anastos, Kathryn] Albert Einstein Coll Med, Dept Med, New York, NY USA. [Anastos, Kathryn] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA. [Rockstroh, Juergen] Univ Hosp Bonn, Dept Internal Med 1, Bonn, Germany. [Santos, Ignacio] Hosp La Princesa, Madrid, Spain. [Oka, Shinichi] Natl Ctr Global Hlth & Med, Tokyo, Japan. [Somi, Geoffrey] Natl AIDS Control Program, Dar Es Salaam, Tanzania. [Stephan, Christoph] Klinikum Johann Wolfgang Goethe Univ, HIVCENTER, Frankfurt, Germany. [Teira, Ramon] Hosp Sierrallana, Torrelavega, Spain. [Wabwire, Deo] MUJHU Res Collaborat, Kampala, Uganda. [Wandeler, Gilles] Univ Hosp Bern, Dept Infect Dis, Bern, Switzerland. [Wandeler, Gilles] Univ Bern, CH-3012 Bern, Switzerland. [Reiss, Peter] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Wood, Robin] Univ Cape Town, Desmond Tutu HIV Ctr, ZA-7700 Rondebosch, South Africa. [Chi, Benjamin H.] Ctr Infect Dis Res Zambia, Lusaka, Zambia. [Williams, Carolyn] NIAID, Epidemiol Branch, Div Aids, NIH, Bethesda, MD 20892 USA. RP Egger, M (reprint author), Univ Bern, Inst Social & Prevent Med, Finkenhubelweg 11, CH-3012 Bern, Switzerland. EM egger@ispm.unibe.ch RI SHCS, int. coll. A/G-4083-2011; SHCS, all/G-4072-2011; Costagliola, Dominique/H-5849-2011; OI Costagliola, Dominique/0000-0003-0765-0869; Keiser, Olivia/0000-0001-8191-2789; Mugglin, Catrina/0000-0001-7966-3939 FU National Cancer Institute (NCI); Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Allergy And Infectious Diseases (NIAID) as part of IeDEA [5U01-AI069919-04, 5U01-AI069924-05, 1U01-AI069927, U01-AI069911-01, 5U01-AI096299]; NIAID [5U01-AI69923-06]; Centers for Disease Control and Prevention [CDC200-2006-18797]; Canadian Institutes of Health Research [TGF-96118, HCP-97105, CBR-86906, CBR-94036, KRS-86251, 169621]; Canadian HIV Trials Network [24]; Government of British Columbia; Dutch Ministry of Foreign Affairs; US National Institutes of Health's NIAID; NCI as part of IeDEA [U01AI069907]; Hong Kong Council for AIDS Trust Fund; Australian Government Department of Health and Ageing; UK Medical Research Council; Department for International Development (DFID) [G0700820, MR/J002380/1] FX The African regions of the International epidemiological Databases to Evaluate AIDS (IeDEA) are supported by the National Cancer Institute (NCI), the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Allergy And Infectious Diseases (NIAID) as part of IeDEA (Grants 5U01-AI069919-04, 5U01-AI069924-05, 1U01-AI069927, U01-AI069911-01, 5U01-AI096299). The Caribbean, Central and South America network of IeDEA is supported by NIAID Grant 5U01-AI69923-06. The North American AIDS Cohort Collaboration on Research and Design of IeDEA is supported by Grants U01-AI069918, U10-AA13566, U01-AI31834, U01-AI34989, U01-AI34993, U01-AI34994, U01-AI35004, U01-AI35039, U01-AI35040, U01-AI35041, U01-AI35042, U01-AI35043, U01-AI37613, U01-AI37984, U01-AI38855, U01-AI38858, U01-AI42590, U01-AI68634, U01-AI68636, U01-HD32632, U10-EY08057, U10-EY08052, U10-EY08067, UL1-RR024131, UL1-RR024131, M01-RR-00052, M01-RR00071, M01-RR00079, M01-RR00083, M01-RR00722, M01-RR025747, P30-AI27757, P30-AI27767, P30-AI27763, P30-AI50410, P30-AI54999, R01-DA04334, R01-DA12568, R01-DA11602, R01-AA16893, R24-AI067039, Z01-CP010176, AHQ290-01-0012, N02-CP55504, AI-69432, AI-69434, K01-AI071725, K23-AI610320, K23-EY013707, K24-DA00432, K01-AI093197, U10-AA13566, R01-AG029154, and K23 AG024896 from the National Institutes of Health; contract CDC200-2006-18797 from the Centers for Disease Control and Prevention; Grants TGF-96118, HCP-97105, CBR-86906, CBR-94036, KRS-86251, and 169621 from the Canadian Institutes of Health Research; the Canadian HIV Trials Network, project 24; and the Government of British Columbia. The TREAT Asia HIV Observational Database, TREAT Asia Studies to Evaluate Resistance, and the Australian HIV Observational Database are initiatives of TREAT Asia, a program of amfAR, The Foundation for AIDS Research, with support from the Dutch Ministry of Foreign Affairs through a partnership with Stichting Aids Fonds, and the US National Institutes of Health's NIAID, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and NCI, as part of IeDEA (U01AI069907). Queen Elizabeth Hospital and the Integrated Treatment Center received additional support from the Hong Kong Council for AIDS Trust Fund. The Kirby Institute is funded by the Australian Government Department of Health and Ageing and is affiliated with the Faculty of Medicine, The University of New South Wales. The ART Cohort Collaboration is supported by UK Medical Research Council and the Department for International Development (DFID), (grants G0700820 and MR/J002380/1). The content of this publication is solely the responsibility of the authors and does not represent the official views of any of the institutions and funders mentioned. NR 36 TC 38 Z9 38 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2014 VL 65 IS 1 BP E8 EP E16 DI 10.1097/QAI.0b013e3182a39979 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AG8DY UT WOS:000335650200003 ER PT J AU Massad, LS Xie, XH Minkoff, H Darragh, TM D'Souza, G Sanchez-Keeland, L Watts, DH Colie, C Strickler, HD AF Massad, L. Stewart Xie, Xianhong Minkoff, Howard Darragh, Teresa M. D'Souza, Gypsyamber Sanchez-Keeland, Lorraine Watts, D. Heather Colie, Christine Strickler, Howard D. TI Abnormal Pap Tests and Human Papillomavirus Infections Among HIV-Infected and Uninfected Women Who Have Sex With Women SO JOURNAL OF LOWER GENITAL TRACT DISEASE LA English DT Article DE human papillomavirus; HIV in women; women who have sex with women ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTERAGENCY HIV; CERVICAL-CANCER; LESBIANS; HEALTH; PREVENTION; GUIDELINES; BEHAVIORS; SOCIETY; ACCESS AB Objective To estimate the frequency of abnormal Pap and human papillomavirus (HPV) positivity among human immunodeficiency virus (HIV)-seropositive and -seronegative women who have sex with women (WSW). Methods Pap and HPV DNA polymerase chain reaction tests were obtained every 6 months from women in a US cohort of HIV-seropositive and -seronegative women. Women who have sex with women were women reporting no male and at least 1 female sex partner for 5 years. They were frequency matched 1:5 to women reporting sex only with men (WSM) and assessed using multivariable generalized estimating equation logistic regression models. Results Paps at study entry were abnormal in 12 (21%) of 49 HIV-seropositive WSW, 151 (64%) of 245 HIV-seropositive WSM, 3 (9%) of 24 HIV-seronegative WSW, and 16 (11%) of 120 HIV-seronegative WSM. Human papillomavirus was found at entry in 18 (42%) HIV-seropositive WSW, 109 (52%) HIV-seropositive WSM, 6 (27%) HIV-seronegative WSW, and 13 (13%) HIV-seronegative WSM. After controlling for HIV serostatus and CD4 count, WSW had marginally lower odds than WSM of Pap abnormality (odds ratio = 0.59, 95% confidence interval = 0.33-1.03) and of HPV (odds ratio = 0.53, 95% confidence interval = 0.32-0.89). After controlling for partner's gender, HIV seropositivity and lower CD4 count were associated with any HPV, oncogenic HPV, any abnormal Pap result, and high-grade squamous intraepithelial lesion or worse (p < .0001 for all). Conclusions Although risks for abnormal Pap and HPV are modestly lower in WSW than in WSM, both are common in HIV-seropositive women regardless of sexual preference. Both WSW and WSM should be screened similarly. C1 [Massad, L. Stewart] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Xie, Xianhong; Strickler, Howard D.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Minkoff, Howard] Maimonides Hosp, Brooklyn, NY 11219 USA. [Darragh, Teresa M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [D'Souza, Gypsyamber] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Sanchez-Keeland, Lorraine] Univ So Calif, Los Angeles, CA USA. [Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Colie, Christine] Georgetown Univ, Washington, DC USA. RP Massad, LS (reprint author), Washington Univ, Sch Med, St Louis, MO 63130 USA. EM massadl@wudosis.wustl.edu FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131]; [R01-CA-085178] FX Major support for this study, including HPV DNA testing, was provided through R01-CA-085178 (H.S.).; Data in the article were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). NR 16 TC 4 Z9 4 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1089-2591 EI 1526-0976 J9 J LOW GENIT TRACT DI JI J. Low. Genit. Tract. Dis. PD JAN PY 2014 VL 18 IS 1 BP 50 EP 56 DI 10.1097/LGT.0b013e3182942733 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH8JF UT WOS:000336383400019 PM 23959300 ER PT J AU Yeo, S Logan, JG AF Yeo, SeonAe Logan, Jeongok G. TI Preventing Obesity SO JOURNAL OF PERINATAL & NEONATAL NURSING LA English DT Article DE exercise; lifestyle; prenatal; sedentary ID GESTATIONAL DIABETES-MELLITUS; BODY-MASS INDEX; PHYSICAL-ACTIVITY; BLOOD-PRESSURE; MATERNAL OBESITY; HISPANIC WOMEN; PUBLIC-HEALTH; LOW-INCOME; RISK; PREGNANCY AB Low-income women are at risk for excessive gestational weight gain. Inactive lifestyle and lack of regular moderate exercise may contribute to the risk of weight gain. This study was conducted to (1) determine the rate and characteristics of low-income pregnant women who exercised regularly and met the American College of Obstetricians and Gynecologists recommendation and (2) describe how these women spent time for other physical activities compared with those who did not exercise regularly. Medicaid-recipient or uninsured pregnant women (n = 816) were asked to complete a physical activity questionnaire at rural and urban county health departments located in North Carolina. Twenty percent of low-income women met the American College of Obstetricians and Gynecologists recommendation for moderate exercise (10 METs-h/wk [metabolic equivalent task-hours per week]). The women who met the recommendation spent 3 hours 45 minutes per week walking as exercise, whereas those who did not meet the recommendation spent 1 hour per week (P < .0001). Women who exercised regularly spent longer hours at work (4.25 vs 1.75 hours per day; P = .019) and on household tasks (5.25 vs 4.0 hours per day; P = .002) than women who did not exercise regularly. Time spent on domestic and occupation activities does not seem to prohibit low-income women from engaging in moderate exercise on a regular basis. C1 [Yeo, SeonAe] Univ N Carolina, Sch Nursing, Chapel Hill, NC 27599 USA. [Logan, Jeongok G.] NINR, NIH, Bethesda, MD 20892 USA. RP Yeo, S (reprint author), Univ N Carolina, Sch Nursing, Carrington Hall,CB 7460, Chapel Hill, NC 27599 USA. EM syeo@email.unc.edu NR 32 TC 2 Z9 2 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0893-2190 EI 1550-5073 J9 J PERINAT NEONAT NUR JI J. Perinat. Neonatal Nurs. PD JAN-MAR PY 2014 VL 28 IS 1 BP 17 EP 25 DI 10.1097/JPN.0000000000000000 PG 9 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA AH2YK UT WOS:000335987900009 PM 24476648 ER PT J AU Furlan, SN Mandraju, R Brewer, T Roybal, K Troutman, TD Hu, W Palm, NW Unni, A Pasare, C AF Furlan, Scott N. Mandraju, Rajakumar Brewer, Travis Roybal, Kole Troutman, Ty Dale Hu, Wei Palm, Noah W. Unni, Arun Pasare, Chandrashekhar TI Enhancement of anti-tumor CD8 immunity by IgG1-mediated targeting of Fc receptors SO MABS LA English DT Article DE Fc receptors; IgG1; dendritic cells; cross-presentation; CD8 T cell priming; cancer vaccine; MHC Class I ID T-CELL-ACTIVATION; DENDRITIC CELLS; CROSS-PRESENTATION; CANCER-IMMUNOTHERAPY; MONOCLONAL-ANTIBODIES; GAMMA RECEPTORS; IN-VIVO; ANTIGEN PRESENTATION; RESPONSES; MICE AB Dendritic cells (DCs) function as professional antigen presenting cells and are critical for linking innate immune responses to the induction of adaptive immunity. Many current cancer DC vaccine strategies rely on differentiating DCs, feeding them tumor antigens ex vivo, and infusing them into patients. Importantly, this strategy relies on prior knowledge of suitable "tumor-specific" antigens to prime an effective anti-tumor response. DCs express a variety of receptors specific for the Fc region of immunoglobulins, and antigen uptake via Fc receptors is highly efficient and facilitates antigen presentation to T cells. Therefore, we hypothesized that expression of the mouse IgG1 Fc region on the surface of tumors would enhance tumor cell uptake by DCs and other myeloid cells and promote the induction of anti-tumor T cell responses. To test this, we engineered a murine lymphoma cell line expressing surface IgG1 Fc and discovered that such tumor cells were taken up rapidly by DCs, leading to enhanced cross-presentation of tumor-derived antigen to CD8+ T cells. IgG1-Fc tumors failed to grow in vivo and prophylactic vaccination of mice with IgG1-Fc tumors resulted in rejection of unmanipulated tumor cells. Furthermore, IgG1-Fc tumor cells were able to slow the growth of an unmanipulated primary tumor when used as a therapeutic tumor vaccine. Our data demonstrate that engagement of Fc receptors by tumors expressing the Fc region of IgG1 is a viable strategy to induce efficient and protective anti-tumor CD8+ T cell responses without prior knowledge of tumor-specific antigens. C1 [Furlan, Scott N.] UT Southwestern Med Ctr, Dept Pediat, Dallas, TX USA. [Mandraju, Rajakumar; Brewer, Travis; Roybal, Kole; Troutman, Ty Dale; Hu, Wei; Pasare, Chandrashekhar] UT Southwestern Med Ctr, Dept Immunol, Dallas, TX 75235 USA. [Palm, Noah W.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Unni, Arun] NHGRI, NIH, Bethesda, MD 20892 USA. RP Pasare, C (reprint author), UT Southwestern Med Ctr, Dept Immunol, Dallas, TX 75235 USA. EM chandrashekhar.pasare@utsouthwestern.edu FU UT Southwestern Medical center; Children's Cancer Fund (Dallas, TX) FX This study was performed by funding from biomedical research endowment to Pasare C from UT Southwestern Medical center. Furlan S was supported by funding from Children's Cancer Fund (Dallas, TX). The authors thank Dr James Forman for critical reading of the manuscript. NR 51 TC 2 Z9 2 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1942-0862 EI 1942-0870 J9 MABS-AUSTIN JI mAbs PD JAN-FEB PY 2014 VL 6 IS 1 BP 108 EP 118 DI 10.4161/mabs.27052 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AH6HH UT WOS:000336230800010 PM 24284965 ER PT J AU Newton, KM Carpenter, JS Guthrie, KA Anderson, GL Caan, B Cohen, LS Ensrud, KE Freeman, EW Joffe, H Sternfeld, B Reed, SD Sherman, S Sammel, MD Kroenke, K Larson, JC LaCroix, AZ AF Newton, Katherine M. Carpenter, Janet S. Guthrie, Katherine A. Anderson, Garnet L. Caan, Bette Cohen, Lee S. Ensrud, Kristine E. Freeman, Ellen W. Joffe, Hadine Sternfeld, Barbara Reed, Susan D. Sherman, Sheryl Sammel, Mary D. Kroenke, Kurt Larson, Joseph C. LaCroix, Andrea Z. TI Methods for the design of vasomotor symptom trials: the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Menopause; Yoga; Exercise; Hot flashes; Clinical trial network; Vasomotor symptoms; Study design; Methodology ID RANDOMIZED CONTROLLED-TRIAL; SLEEP QUALITY INDEX; HOT FLASHES; BREAST-CANCER; DOUBLE-BLIND; CHECKLIST HSCL; BRIEF PAIN; PHASE-III; VALIDATION; LIFE AB Objective: This report describes the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network and methodological issues addressed in designing and implementing vasomotor symptom trials. Methods: Established in response to a National Institutes of Health request for applications, the network was charged with conducting rapid throughput randomized trials of novel and understudied available interventions postulated to alleviate vasomotor and other menopausal symptoms. Included are descriptions of and rationale for criteria used for interventions and study selection, common eligibility and exclusion criteria, common primary and secondary outcome measures, consideration of placebo response, establishment of a biorepository, trial duration, screening and recruitment, statistical methods, and quality control. All trial designs are presented, including the following: (1) a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effectiveness of the selective serotonin reuptake inhibitor escitalopram in reducing vasomotor symptom frequency and severity; (2) a two-by-three factorial design trial to test three different interventions (yoga, exercise, and omega-3 supplementation) for the improvement of vasomotor symptom frequency and bother; and (3) a three-arm comparative efficacy trial of the serotonin-norepinephrine reuptake inhibitor venlafaxine and low-dose oral estradiol versus placebo for reducing vasomotor symptom frequency. The network's structure and governance are also discussed. Conclusions: The methods used in and the lessons learned from the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health trials are shared to encourage and support the conduct of similar trials and to encourage collaborations with other researchers. C1 [Newton, Katherine M.] Grp Hlth Res Inst, Seattle, WA USA. [Carpenter, Janet S.] Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. [Guthrie, Katherine A.; Anderson, Garnet L.; Larson, Joseph C.; LaCroix, Andrea Z.] Fred Hutchinson Canc Res Ctr, Data Coordinating Ctr, Seattle, WA 98104 USA. [Caan, Bette; Sternfeld, Barbara] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Cohen, Lee S.; Joffe, Hadine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Ensrud, Kristine E.] Univ Minnesota, VA Med Ctr, Minneapolis, MN USA. [Freeman, Ellen W.] Univ Penn, Sch Med, Dept Obstet Gynecol, Philadelphia, PA 19104 USA. [Freeman, Ellen W.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Reed, Susan D.] Univ Washington, Sch Publ Hlth & Community Med, Dept Obstet Gynecol, Seattle, WA 98195 USA. [Reed, Susan D.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Sherman, Sheryl] NIA, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Sammel, Mary D.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Stat, Philadelphia, PA 19104 USA. [Kroenke, Kurt] VA Ctr Excellence Implementing Evidence Based Pra, Indianapolis, IN USA. [Kroenke, Kurt] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. RP Newton, KM (reprint author), Grp Hlth Res Inst, Seattle, WA USA. EM newton.k@ghc.org FU National Institutes of Health, National Institute on Aging; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Center for Complementary and Alternative Medicine; Office of Research on Women's Health [U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700] FX This study was funded by the National Institutes of Health as a cooperative agreement issued by the National Institute on Aging, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Center for Complementary and Alternative Medicine, and the Office of Research on Women's Health (U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, and U01AG032700). NR 59 TC 22 Z9 22 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN PY 2014 VL 21 IS 1 BP 45 EP 58 DI 10.1097/gme.0b013e31829337a4 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH6AQ UT WOS:000336213500009 PM 23760428 ER PT J AU Jing, X Cimino, JJ AF Jing, X. Cimino, J. J. TI A Complementary Graphical Method for Reducing and Analyzing Large Data Sets Case Studies Demonstrating Thresholds Setting and Selection SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE Data mining method; data filtering method; threshold setting; threshold selection; data visualization; hierarchical terminology; data analysis; clinical data repository AB Objectives: Graphical displays can make data more understandable; however, large graphs can challenge human comprehension. We have previously described a filtering method to provide high-level summary views of large data sets. In this paper we demonstrate our method for setting and selecting thresholds to limit graph size while retaining important information by applying it to large single and paired data sets, taken from patient and bibliographic databases. Methods: Four case studies are used to illustrate our method. The data are either patient discharge diagnoses (coded using the Inter, national Classification of Diseases, Clinical Modifications [ICD9-CM]) or Medline citations (coded using the Medical Subject Headings [MeSH]). We use combinations of different thresholds to obtain filtered graphs for detailed analysis. The thresholds setting and selection, such as thresholds for node counts, class counts, ratio values, p values (for diff data sets), and percentiles of selected class count thresholds, are demonstrated with details in case studies. The main steps include: data preparation, data manipulation, computation, and threshold selection and visualization. We also describe the data models for different types of thresholds and the considerations for thresholds selection. Results: The filtered graphs are 1%-3% of the size of the original graphs. For our case studies, the graphs provide 1) the most heavily used ICD9-CM codes, 2) the codes with most patients in a research hospital in 2011,3) a profile of publications on "heavily represented topics" in MEDLINE in 2011, and 4) validated knowledge about adverse effects of the medication of rosiglitazone and new interesting areas in the ICD9-CM hierarchy associated with patients taking the medication of pioglitazone. Conclusions: Our filtering method reduces large graphs to a manageable size by removing relatively unimportant nodes. The graphical method provides summary views based on computation of usage frequency and semantic context of hierarchical terminology. The method is applicable to large data sets (such as a hundred thousand records or more) and can be used to generate new hypotheses from data sets coded with hierarchical terminologies. C1 Natl Lib Med, Lab Informat Dev, NIH, Bethesda, MD USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Jing, X (reprint author), Ohio Univ, Coll Hlth Sci & Profess, Dept Social & Publ Hlth, Grover Ctr W357, Athens, OH 45701 USA. EM jingx@ohio.edu OI Jing, Xia/0000-0002-1916-4588; Cimino, James/0000-0003-4101-1622 FU National Library of Medicine; NIH Clinical Center FX This work was supported by intramural research funds from the National Library of Medicine and the NIH Clinical Center. Authors would like to thank Drs. Olivier Bodenreider, Bastien Rance, Kin Wah Fung and Swapna Abhyankar for helpful and constructive discussions; thank Dr. Fiona Callaghan for statistical consultations and suggestions; thank Mr. Dwayne McCully, Chuck Gibbs and Kevin Sung for technical support. NR 23 TC 1 Z9 1 U1 0 U2 5 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2014 VL 53 IS 3 BP 173 EP 185 DI 10.3414/ME13-01-0075 PG 13 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA AH7ZH UT WOS:000336353400005 PM 24727931 ER PT J AU Resnik, DB AF Resnik, David B. TI Genetics and personal responsibility for health SO NEW GENETICS AND SOCIETY LA English DT Article DE genetics; moral responsibility; health; genetic testing; breast cancer; lifestyle; ethics ID PUBLIC-HEALTH; CARE; DISCRIMINATION; STIGMA; ETHICS AB Advances in genetic medicine may have implications for how we should think about personal responsibility for health, because they may show how it is possible to exert some control over risk factors that were previously thought as beyond the individual's control. Although we cannot control the genes that we are born with, we can often make decisions concerning genetic testing, disease prevention, and treatment. One might argue, therefore, that individuals should be treated as morally responsible for taking effective action in response to genetic risks factors, since genetically based health risks are similar to other health risks. While this argument makes sense as an abstract, philosophical position, it is not a useful guide to public policy. Given these concerns, there is little society can or should do to encourage individuals to address their genetic risk factors, other than praising those who make prudent choices. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,Mail Drop CU 03, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [ZIA ES102646-06] NR 30 TC 2 Z9 2 U1 3 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1463-6778 EI 1469-9915 J9 NEW GENET SOC JI New Genet. Soc. PY 2014 VL 33 IS 2 BP 113 EP 125 DI 10.1080/14636778.2014.905195 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; History & Philosophy Of Science; Social Issues; Social Sciences, Biomedical SC Biotechnology & Applied Microbiology; Genetics & Heredity; History & Philosophy of Science; Social Issues; Biomedical Social Sciences GA AH8HD UT WOS:000336376800001 PM 25598702 ER PT J AU Segal, L Katz, LS Lupu-Meiri, M Shapira, H Sandbank, J Gershengorn, MC Oron, Y AF Segal, Liora Katz, Liora S. Lupu-Meiri, Monica Shapira, Hagit Sandbank, Judith Gershengorn, Marvin C. Oron, Yoram TI Proteinase-Activated Receptors Differentially Modulate In Vitro Invasion of Human Pancreatic Adenocarcinoma PANC-1 Cells in Correlation With Changes in the Expression of CDC42 Protein SO PANCREAS LA English DT Article DE pancreatic adenocarcinoma; PANC-1 cell line; proteinase-activated receptors; invasion; migration; CDC42 ID CANCER CELLS; PROLIFERATION; PAR1; MIGRATION; TRYPSIN; AGGREGATION; METASTASIS; MECHANISMS; CARCINOMA; MOTILITY AB Objectives Proteinase-activated receptor-1 (PAR-1) and PAR-2 have been associated with increased invasiveness and metastasis in human malignancies. The role of PAR-3 has been less investigated. We examined the role of PARs in a human pancreatic adenocarcinoma PANC-1 cell line phenotype in vitro. Methods We knocked down PAR-1, PAR-2, or PAR-3, whereas empty vector-infected cells served as controls. Specific peptide agonists of PARs were used to stimulate the receptors. In vitro assays of colony formation, migration, and invasion were used to characterize the phenotypes, and Western analysis was used to follow cell division control protein 42 homolog (CDC42) expression. Results PAR-1 and PAR-2 knockdowns (KDs) were markedly less, whereas PAR-3 KDs were robustly more migratory and invasive than the controls. Stimulation of PAR-1 or PAR-2 by their peptide agonists increased, whereas PAR-3 agonist reduced the invasion of the control cells. Knockdowns of all three PARs exhibited changes in the expression of CDC42, which correlated with the changes in their invasion. Conversely, stimulation of vector-control cells with PAR-1 or PAR-2 agonists enhanced, whereas PAR-3 agonist reduced the expression of CDC42. In the respective KD cells, the effects of the agonists were abrogated. Conclusion The expression and/or activation of PARs is linked to the invasiveness of PANC-1 cells in vitro, probably via modulation of the expression of CDC42. C1 [Segal, Liora; Lupu-Meiri, Monica; Oron, Yoram] Tel Aviv Univ, Dept Physiol & Pharmacol, Sackler Fac Med, IL-69978 Ramat Aviv, Israel. [Katz, Liora S.; Gershengorn, Marvin C.] NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA. [Shapira, Hagit] Inst Pathol, Cent Lab, Rehovot, Israel. [Sandbank, Judith] Tel Aviv Univ, Assaf Harofe Hosp, Inst Pathol, Ramat Aviv, Israel. [Sandbank, Judith] Tel Aviv Univ, Dept Pathol, Sackler Fac Med, Ramat Aviv, Israel. RP Oron, Y (reprint author), Tel Aviv Univ, Dept Physiol & Pharmacol, Sackler Fac Med, IL-69978 Ramat Aviv, Israel. EM medfair@post.tau.ac.il FU Andy Lebach Chair of Clinical Pharmacology and Toxicology, Tel Aviv University FX This study was supported in part by the Andy Lebach Chair of Clinical Pharmacology and Toxicology, Tel Aviv University, to Professor Yoram Oron (incumbent). NR 33 TC 2 Z9 3 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD JAN PY 2014 VL 43 IS 1 BP 103 EP 108 DI 10.1097/MPA.0b013e31829f0b81 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH6CV UT WOS:000336219200016 PM 23921961 ER PT J AU Freedman, AH Gronau, I Schweizer, RM Ortega-Del Vecchyo, D Han, EJ Silva, PM Galaverni, M Fan, ZX Marx, P Lorente-Galdos, B Beale, H Ramirez, O Hormozdiari, F Alkan, C Vila, C Squire, K Geffen, E Kusak, J Boyko, AR Parker, HG Lee, C Tadigotla, V Siepel, A Bustamante, CD Harkins, TT Nelson, SF Ostrander, EA Marques-Bonet, T Wayne, RK Novembre, J AF Freedman, Adam H. Gronau, Ilan Schweizer, Rena M. Ortega-Del Vecchyo, Diego Han, Eunjung Silva, Pedro M. Galaverni, Marco Fan, Zhenxin Marx, Peter Lorente-Galdos, Belen Beale, Holly Ramirez, Oscar Hormozdiari, Farhad Alkan, Can Vila, Carles Squire, Kevin Geffen, Eli Kusak, Josip Boyko, Adam R. Parker, Heidi G. Lee, Clarence Tadigotla, Vasisht Siepel, Adam Bustamante, Carlos D. Harkins, Timothy T. Nelson, Stanley F. Ostrander, Elaine A. Marques-Bonet, Tomas Wayne, Robert K. Novembre, John TI Genome Sequencing Highlights the Dynamic Early History of Dogs SO PLOS GENETICS LA English DT Article ID DOMESTIC DOGS; DNA; EVOLUTION; INFERENCE; GENETICS; CANIDS; ORIGIN; WOLVES; GENES; WILD AB To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we generated high-quality genome sequences from three gray wolves, one from each of the three putative centers of dog domestication, two basal dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. Analysis of these sequences supports a demographic model in which dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow. In dogs, the domestication bottleneck involved at least a 16-fold reduction in population size, a much more severe bottleneck than estimated previously. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was substantially larger than represented by modern wolf populations. We narrow the plausible range for the date of initial dog domestication to an interval spanning 11-16 thousand years ago, predating the rise of agriculture. In light of this finding, we expand upon previous work regarding the increase in copy number of the amylase gene (AMY2B) in dogs, which is believed to have aided digestion of starch in agricultural refuse. We find standing variation for amylase copy number variation in wolves and little or no copy number increase in the Dingo and Husky lineages. In conjunction with the estimated timing of dog origins, these results provide additional support to archaeological finds, suggesting the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that, surprisingly, none of the extant wolf lineages from putative domestication centers is more closely related to dogs, and, instead, the sampled wolves form a sister monophyletic clade. This result, in combination with dog-wolf admixture during the process of domestication, suggests that a re-evaluation of past hypotheses regarding dog origins is necessary. C1 [Freedman, Adam H.; Schweizer, Rena M.; Ortega-Del Vecchyo, Diego; Han, Eunjung; Wayne, Robert K.; Novembre, John] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. [Gronau, Ilan; Siepel, Adam] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY USA. [Silva, Pedro M.] Univ Porto, CIBIO UP, Vairao, Portugal. [Galaverni, Marco] ISPRA, Ozzano Dell Emilia, Italy. [Fan, Zhenxin] Sichuan Univ, Key Lab Bioresources & Ecoenvironm, Chengdu 610064, Peoples R China. [Marx, Peter] Budapest Univ Technol & Econ, Dept Measurement & Informat Syst, Budapest, Hungary. [Lorente-Galdos, Belen; Ramirez, Oscar; Marques-Bonet, Tomas] Univ Pompeu Fabra, CSIC, Inst Biol Evolut, Barcelona, Spain. [Beale, Holly; Parker, Heidi G.; Ostrander, Elaine A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Hormozdiari, Farhad] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90024 USA. [Alkan, Can] Bilkent Univ, Ankara, Turkey. [Vila, Carles] CSIC, EBD, E-41080 Seville, Spain. [Squire, Kevin; Nelson, Stanley F.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. [Geffen, Eli] Tel Aviv Univ, Dept Zool, IL-69978 Tel Aviv, Israel. [Kusak, Josip] Univ Zagreb, Zagreb 41000, Croatia. [Boyko, Adam R.] Cornell Univ, Dept Vet Med, Ithaca, NY USA. [Lee, Clarence; Tadigotla, Vasisht; Harkins, Timothy T.] Life Technol, Foster City, CA USA. [Bustamante, Carlos D.] Stanford Sch Med, Stanford, CA USA. [Marques-Bonet, Tomas] ICREA, Barcelona 08010, Spain. RP Freedman, AH (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. EM rwayne@ucla.edu; jnovembre@uchicago.edu RI Alkan, Can/D-2982-2009; Marques-Bonet, Tomas/I-4618-2014; Ramirez, Oscar/E-7293-2012; Vila, Carles/H-4893-2013; CSIC, EBD Donana/C-4157-2011; OI Alkan, Can/0000-0002-5443-0706; Ostrander, Elaine/0000-0001-6075-9738; Marques-Bonet, Tomas/0000-0002-5597-3075; Ramirez, Oscar/0000-0001-5164-6790; Vila, Carles/0000-0002-4206-5246; CSIC, EBD Donana/0000-0003-4318-6602; Freedman, Adam /0000-0003-4714-3925; Siepel, Adam/0000-0002-3557-7219; Lorente-Galdos, Belen/0000-0001-5390-2452; Kusak, Josip/0000-0002-5544-6486 FU NSF [DBI-0905784, EF-1021397, DEB-0948510]; Searle Foundation Scholar Award; NIH [T32 HG002536]; NIH (NIGMS) [GM102192]; UC MEXUS-CONACYT [213627]; Fundacao para a Ciencia e a Tecnologia (Portugal) [SFRH/BD/60549/2009]; University of Bologna (Italy), XXIV cicle, Biodiversity and Evolution; National Science and Technology Support Project of China [2012BAC01B06]; Rosztoczy Foundation; USHHS Ruth L. Kirschstein Institutional National Research Service Award [T32 CA009056]; National Institute of Bioinformatics; National Human Genome Research Institute; JAEDOC-CSIC; Marie Curie CIG, Programa de Captacion del Conocimiento para Andalucia-a for sequencing of Chinese wolf at BGI [PCIG10-GA-2011-303772]; ERC [260372]; MICINN (Spain) [BFU2011-28549] FX This work was supported by an NSF Postdoctoral Fellowship DBI-0905784 (AHF), NSF Graduate Research Fellowship (RMS), Searle Foundation Scholar Award (JN), NSF grant EF-1021397 (JN RKW AHF RMS EH), NIH T32 HG002536 (EH), NIH (NIGMS) grant GM102192 (IG AS), UC MEXUS-CONACYT doctoral fellowship 213627 (DODV), PhD grant from Fundacao para a Ciencia e a Tecnologia (Portugal) SFRH/BD/60549/2009 (PMS), PhD Grant from University of Bologna (Italy), XXIV cicle, Biodiversity and Evolution (MG), National Science and Technology Support Project of China 2012BAC01B06 (ZF), Rosztoczy Foundation (PM), USHHS Ruth L. Kirschstein Institutional National Research Service Award #T32 CA009056 (KS), National Institute of Bioinformatics (BLG), Intramural Program of the National Human Genome Research Institute (HB HGP EAO), JAEDOC-CSIC (EFS) (OR), Marie Curie CIG PCIG10-GA-2011-303772 (CA) Programa de Captacion del Conocimiento para Andalucia-a for sequencing of Chinese wolf at BGI, ERC Starting Grant 260372 and MICINN (Spain) BFU2011-28549 (TMB), and NSF grant DEB-0948510 (ARB CDB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 116 Z9 119 U1 32 U2 230 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2014 VL 10 IS 1 AR e1004016 DI 10.1371/journal.pgen.1004016 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA AI0GU UT WOS:000336525000012 PM 24453982 ER PT J AU Mazan-Mamczarz, K Zhao, XF Dai, BJ Steinhardt, JJ Peroutka, RJ Berk, KL Landon, AL Sadowska, M Zhang, YQ Lehrmann, E Becker, KG Shaknovich, R Liu, ZQ Gartenhaus, RB AF Mazan-Mamczarz, Krystyna Zhao, X. Frank Dai, Bojie Steinhardt, James J. Peroutka, Raymond J. Berk, Kimberly L. Landon, Ari L. Sadowska, Mariola Zhang, Yongqing Lehrmann, Elin Becker, Kevin G. Shaknovich, Rita Liu, Zhenqiu Gartenhaus, Ronald B. TI Down-Regulation of eIF4GII by miR-520c-3p Represses Diffuse Large B Cell Lymphoma Development SO PLOS GENETICS LA English DT Article ID INITIATION-FACTOR EIF4E; TRANSLATION INITIATION; MALIGNANT-TRANSFORMATION; THERAPEUTIC SUPPRESSION; MICRORNA SIGNATURES; INDUCED SENESCENCE; CANCER-THERAPY; IN-VIVO; EXPRESSION; DEREGULATION AB Deregulation of the translational machinery is emerging as a critical contributor to cancer development. The contribution of microRNAs in translational gene control has been established however; the role of microRNAs in disrupting the cap-dependent translation regulation complex has not been previously described. Here, we established that elevated miR-520c-3p represses global translation, cell proliferation and initiates premature senescence in HeLa and DLBCL cells. Moreover, we demonstrate that miR-520c-3p directly targets translation initiation factor, eIF4GII mRNA and negatively regulates eIF4GII protein synthesis. miR-520c-3p overexpression diminishes cells colony formation and reduces tumor growth in a human xenograft mouse model. Consequently, downregulation of eIF4GII by siRNA decreases translation, cell proliferation and ability to form colonies, as well as induces cellular senescence. In vitro and in vivo findings were further validated in patient samples; DLBCL primary cells demonstrated low miR-520c-3p levels with reciprocally up-regulated eIF4GII protein expression. Our results provide evidence that the tumor suppressor effect of miR-520c-3p is mediated through repression of translation while inducing senescence and that eIF4GII is a key effector of this anti-tumor activity. C1 [Mazan-Mamczarz, Krystyna; Dai, Bojie; Steinhardt, James J.; Peroutka, Raymond J.; Berk, Kimberly L.; Landon, Ari L.; Sadowska, Mariola; Liu, Zhenqiu; Gartenhaus, Ronald B.] Univ Maryland, Dept Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Zhao, X. Frank] Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. [Zhang, Yongqing; Lehrmann, Elin; Becker, Kevin G.] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA. [Gartenhaus, Ronald B.] Vet Adm Med Ctr, Baltimore, MD 21218 USA. [Shaknovich, Rita] Weill Cornell Med Coll, New York, NY USA. RP Mazan-Mamczarz, K (reprint author), Univ Maryland, Dept Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. EM rgartenhaus@som.umaryland.edu OI Lehrmann, Elin/0000-0002-9869-9475; Becker, Kevin/0000-0002-6794-6656 FU Department of Veterans Affairs from the NIH [R01AA017972, RO1CA164311]; National Institute on Aging-Intramural Research Program, NIH FX This work was supported in part by a Merit Review Award from the Department of Veterans Affairs (RBG), R01AA017972 and RO1CA164311 from the NIH (RBG). KGB, YZ and EL were supported by the National Institute on Aging-Intramural Research Program, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 15 Z9 16 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2014 VL 10 IS 1 AR e1004105 DI 10.1371/journal.pgen.1004105 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA AI0GU UT WOS:000336525000061 PM 24497838 ER PT J AU Service, SK Teslovich, TM Fuchsberger, C Ramensky, V Yajnik, P Koboldt, DC Larson, DE Zhang, QY Lin, L Welch, R Ding, L McLellan, MD O'Laughlin, M Fronick, C Fulton, LL Magrini, V Swift, A Elliott, P Jarvelin, MR Kaakinen, M McCarthy, MI Peltonen, L Pouta, A Bonnycastle, LL Collins, FS Narisu, N Stringham, HM Tuomilehto, J Ripatti, S Fulton, RS Sabatti, C Wilson, RK Boehnke, M Freimer, NB AF Service, Susan K. Teslovich, Tanya M. Fuchsberger, Christian Ramensky, Vasily Yajnik, Pranav Koboldt, Daniel C. Larson, David E. Zhang, Qunyuan Lin, Ling Welch, Ryan Ding, Li McLellan, Michael D. O'Laughlin, Michele Fronick, Catrina Fulton, Lucinda L. Magrini, Vincent Swift, Amy Elliott, Paul Jarvelin, Marjo-Riitta Kaakinen, Marika McCarthy, Mark I. Peltonen, Leena Pouta, Anneli Bonnycastle, Lori L. Collins, Francis S. Narisu, Narisu Stringham, Heather M. Tuomilehto, Jaakko Ripatti, Samuli Fulton, Robert S. Sabatti, Chiara Wilson, Richard K. Boehnke, Michael Freimer, Nelson B. TI Re-sequencing Expands Our Understanding of the Phenotypic Impact of Variants at GWAS Loci SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; FOUNDER POPULATION; HDL CHOLESTEROL; RARE; DISEASE; GENETICS; CONTRIBUTES; GLUCOSE; TRAITS; EXOMES AB Genome-wide association studies (GWAS) have identified >500 common variants associated with quantitative metabolic traits, but in aggregate such variants explain at most 20-30% of the heritable component of population variation in these traits. To further investigate the impact of genotypic variation on metabolic traits, we conducted re-sequencing studies in >6,000 members of a Finnish population cohort (The Northern Finland Birth Cohort of 1966 [NFBC]) and a type 2 diabetes case-control sample (The Finland-United States Investigation of NIDDM Genetics [FUSION] study). By sequencing the coding sequence and 5' and 3' untranslated regions of 78 genes at 17 GWAS loci associated with one or more of six metabolic traits (serum levels of fasting HDL-C, LDL-C, total cholesterol, triglycerides, plasma glucose, and insulin), and conducting both single-variant and gene-level association tests, we obtained a more complete understanding of phenotype-genotype associations at eight of these loci. At all eight of these loci, the identification of new associations provides significant evidence for multiple genetic signals to one or more phenotypes, and at two loci, in the genes ABCA1 and CETP, we found significant gene-level evidence of association to non-synonymous variants with MAF<1%. Additionally, two potentially deleterious variants that demonstrated significant associations (rs138726309, a missense variant in G6PC2, and rs28933094, a missense variant in LIPC) were considerably more common in these Finnish samples than in European reference populations, supporting our prior hypothesis that deleterious variants could attain high frequencies in this isolated population, likely due to the effects of population bottlenecks. Our results highlight the value of large, well-phenotyped samples for rare-variant association analysis, and the challenge of evaluating the phenotypic impact of such variants. C1 [Service, Susan K.; Ramensky, Vasily; Freimer, Nelson B.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA 90024 USA. [Teslovich, Tanya M.; Fuchsberger, Christian; Yajnik, Pranav; Welch, Ryan; Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Teslovich, Tanya M.; Fuchsberger, Christian; Yajnik, Pranav; Welch, Ryan; Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Koboldt, Daniel C.; Larson, David E.; Zhang, Qunyuan; Lin, Ling; Ding, Li; McLellan, Michael D.; O'Laughlin, Michele; Fronick, Catrina; Fulton, Lucinda L.; Magrini, Vincent; Fulton, Robert S.; Wilson, Richard K.] Washington Univ, Genome Inst, St Louis, MO USA. [Swift, Amy; Bonnycastle, Lori L.; Collins, Francis S.; Narisu, Narisu] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Elliott, Paul; Jarvelin, Marjo-Riitta; Kaakinen, Marika] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London, England. [Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, Fac Med, London, England. [Jarvelin, Marjo-Riitta; Kaakinen, Marika] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Jarvelin, Marjo-Riitta; Kaakinen, Marika] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Jarvelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, Oulu, Finland. [Jarvelin, Marjo-Riitta; Pouta, Anneli; Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Dept Children & Young People & Families, Oulu, Finland. [McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Peltonen, Leena; Ripatti, Samuli] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland. [Peltonen, Leena] Broad Inst MIT & Harvard, Program Human & Populat Genet, Cambridge, MA USA. [Pouta, Anneli] Univ Oulu, Inst Clin Med Obstet & Gynecol, Oulu, Finland. [Ripatti, Samuli] Univ Helsinki, Hjelt Inst, Helsinki, Finland. [Ripatti, Samuli] Wellcome Trust Sanger Inst, Hinxton, England. [Sabatti, Chiara] Stanford Univ, Dept Hlth & Res Policy, Stanford, CA 94305 USA. RP Service, SK (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA 90024 USA. EM rwilson@wustl.edu; boenke@umich.edu; nfreimer@mednet.ucla.edu RI Ripatti, Samuli/H-9446-2014; OI Ripatti, Samuli/0000-0002-0504-1202; Fuchsberger, Christian/0000-0002-5918-8947; Kaakinen, Marika/0000-0002-9228-0462; Jarvelin, Marjo-Riitta/0000-0002-2149-0630 FU U.S. National Institutes of Health [DK062370, HL087679, MH083268, U54HG003079, MH63706, HG006695, HL113315]; Academy of Finland [104781, 120315, 129269, 1114194]; Center of Excellence in Complex Disease Genetics; SALVE [251217]; Finnish Foundation for Cardiovascular Research; Sigrid Juselius Foundation; Wellcome Trust [098381]; European Commission [ENGAGE HEALTH-F4-2007-201413]; EURO-BLCS [QLG1-CT-2000-01643]; University Hospital Oulu, Biocenter, University of Oulu, Finland [75617]; European Union [277849]; Medical Research Council, UK [G0500539, G0600705] FX We received financial support from the following sources: The U.S. National Institutes of Health (grants DK062370 [MB]; HL087679 [LP]; MH083268 [NBF]; U54HG003079 [RKW]; MH63706 [Susan L. Smalley]), HG006695 [CS], HL113315 [NBF, AP]; The Academy of Finland (grants 104781, 120315, 129269, 1114194, Center of Excellence in Complex Disease Genetics and SALVE [MRJ]; grant 251217 [SR]), The Finnish Foundation for Cardiovascular Research and the Sigrid Juselius Foundation (SR), The Wellcome Trust (grant 098381 [MIM]), The European Commission (ENGAGE HEALTH-F4-2007-201413 [MIM]; EURO-BLCS, Framework 5 award QLG1-CT-2000-01643 [MRJ]), University Hospital Oulu, Biocenter, University of Oulu, Finland (grant 75617 [MRJ]), The European Union (Framework Programme 7 small-scale focused research collaborative project EurHEALTHAgeing 277849 [MRJ]), and The Medical Research Council, UK (grants G0500539, G0600705, PrevMetSyn/SALVE [MRJ]). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 20 Z9 20 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2014 VL 10 IS 1 AR e1004147 DI 10.1371/journal.pgen.1004147 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA AI0GU UT WOS:000336525000077 PM 24497850 ER PT J AU Gluck, ME Yahav, E Hashim, SA Geliebter, A AF Gluck, Marci E. Yahav, Eric Hashim, Sami A. Geliebter, Allan TI Ghrelin Levels After a Cold Pressor Stress Test in Obese Women With Binge Eating Disorder SO PSYCHOSOMATIC MEDICINE LA English DT Article DE stress responsivity; stress hormones; appetite; peptide hormones; hunger; eating disorders ID STIMULATES LOCOMOTOR-ACTIVITY; INCREASES FOOD-INTAKE; BULIMIA-NERVOSA; PLASMA GHRELIN; PSYCHOSOCIAL STRESS; CIRCULATING GHRELIN; CORTISOL; HUMANS; INDIVIDUALS; SECRETION AB Objective Ghrelin, a peptide hormone secreted mainly by the stomach, increases appetite and food intake. Surprisingly, ghrelin levels are lower in obese individuals with binge eating disorder (BED) than in obese non-BED individuals. Acute psychological stress has been shown to raise ghrelin levels in animals and humans. Our aim was to assess ghrelin levels after a cold pressor test (CPT) in women with BED. We also examined the relationship between the cortisol stress response and changes in ghrelin levels. Methods Twenty-one obese (mean [standard deviation] body mass index = 34.9 [5.8] kg/m(2)) women (10 non-BED, 11 BED) underwent the CPT, hand submerged in ice water for 2 minutes. Blood samples were drawn for 70 minutes and assayed for ghrelin and cortisol. Results There were no differences between the groups in ghrelin levels at baseline (-10 minutes). Ghrelin rose significantly after the CPT (F = 2.4, p = .024) peaking at 19 minutes before declining (F = 17.9, p < .001), but there were no differences between the BED and non-BED groups. Area under the curve for ghrelin was not related to ratings of pain, stress, hunger, or desire to eat after CPT. In addition, there were no observed relationships between the area under the curves for ghrelin or cortisol after stress. Conclusions Although there were no differences between BED groups, there was a significant rise in ghrelin in obese humans after a stressor, consistent with other recent reports suggesting a stress-related role for ghrelin. C1 [Gluck, Marci E.] NIDDK, NIH, Obes & Diabet Clin Res Sect, Phoenix, AZ 85016 USA. [Yahav, Eric; Hashim, Sami A.] Columbia Univ, Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, New York Obes Res Ctr,Dept Med, New York, NY USA. [Geliebter, Allan] Columbia Univ, Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, New York Obes Nutr Res Ctr,Dept Med, New York, NY USA. [Geliebter, Allan] Columbia Univ, Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, New York Obes Nutr Res Ctr,Dept Psychiat, New York, NY USA. [Geliebter, Allan] Touro Coll, New York, NY USA. RP Gluck, ME (reprint author), NIDDK, NIH, Obes & Diabet Clin Res Sect, 4212 North 16th St,Room 541, Phoenix, AZ 85016 USA. EM gmarci@mail.nih.gov FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health [DK068392, DK074046, DK54318]; [DK 07559] FX This study was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. In addition, it was supported by National Institutes of Health (Grant Nos. DK068392, DK074046, and DK54318; to A. G. and a training grant (DK 07559; to M. G.). The NY Obesity Nutrition Research Center (DK 26687) provided body composition services (SB Heymsfield) and hormone assays (FX Pi-Sunyer). The General Clinical Research Center (J. Albu) provided supplies, nursing services, and clinical space (MO1 RR0064529). Boost was contributed by Mead Johnson. The authors report no conflicts of interest and no source of funding. NR 53 TC 7 Z9 7 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN PY 2014 VL 76 IS 1 BP 74 EP 79 DI 10.1097/PSY.0000000000000018 PG 6 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AH6TG UT WOS:000336263000009 PM 24367126 ER PT J AU Lackemeyer, MG de Kok-Mercado, F Wada, J Bollinger, L Kindrachuk, J Wahl-Jensen, V Kuhn, JH Jahrling, PB AF Lackemeyer, Matthew G. de Kok-Mercado, Fabian Wada, Jiro Bollinger, Laura Kindrachuk, Jason Wahl-Jensen, Victoria Kuhn, Jens H. Jahrling, Peter B. TI ABSL-4 Aerobiology Biosafety and Technology at the NIH/NIAID Integrated Research Facility at Fort Detrick SO VIRUSES-BASEL LA English DT Article DE ABSL-4; aerobiology; biosafety level 4; class III biosafety cabinet; BSL-4; high-consequence viral pathogens; medical countermeasure; viral hemorrhagic fever ID AEROSOL EXPOSURE; VIRUS; PROGRAM; AGENTS; SYSTEM; MODEL AB The overall threat of a viral pathogen to human populations is largely determined by the modus operandi and velocity of the pathogen that is transmitted among humans. Microorganisms that can spread by aerosol are considered a more challenging enemy than those that require direct body-to-body contact for transmission, due to the potential for infection of numerous people rather than a single individual. Additionally, disease containment is much more difficult to achieve for aerosolized viral pathogens than for pathogens that spread solely via direct person-to-person contact. Thus, aerobiology has become an increasingly necessary component for studying viral pathogens that are naturally or intentionally transmitted by aerosol. The goal of studying aerosol viral pathogens is to improve public health preparedness and medical countermeasure development. Here, we provide a brief overview of the animal biosafety level 4 Aerobiology Core at the NIH/NIAID Integrated Research Facility at Fort Detrick, Maryland, USA. C1 [Lackemeyer, Matthew G.; de Kok-Mercado, Fabian; Wada, Jiro; Bollinger, Laura; Kindrachuk, Jason; Wahl-Jensen, Victoria; Kuhn, Jens H.; Jahrling, Peter B.] NIAID, Integrated Res Facil Ft Detrick, Div Clin Res, NIH, Ft Detrick, MD 21702 USA. RP Jahrling, PB (reprint author), NIAID, Integrated Res Facil Ft Detrick, Div Clin Res, NIH, Ft Detrick, MD 21702 USA. EM matthew.lackemeyer@nih.gov; fabiandekok@gmail.com; wadaj@niaid.nih.gov; bollingerl@niaid.nih.gov; kindrachuk.kenneth@nih.gov; Victoria.Jensen@nbacc.dhs.gov; kuhnjens@niaid.nih.gov; jahrlingp@niaid.nih.gov RI Kuhn, Jens H./B-7615-2011; OI Kuhn, Jens H./0000-0002-7800-6045; Kindrachuk, Jason/0000-0002-3305-7084 FU NIAID [HHSN272200700016I] FX The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services or of the institutions and companies affiliated with the authors. MGL performed this work as an employee of Lovelace Respiratory Research Institute; VWJ and JHK as employees of Tunnell Consulting, Inc.; and FKM, JW, LB, and JK as employees of Battelle Memorial Institute; all under Battelle's Memorial Institute's prime contract with NIAID, under Contract No. HHSN272200700016I. NR 25 TC 2 Z9 2 U1 0 U2 4 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD JAN PY 2014 VL 6 IS 1 BP 137 EP 150 DI 10.3390/v6010137 PG 14 WC Virology SC Virology GA AH4JM UT WOS:000336093200007 PM 24402304 ER PT S AU Earle, CC Travis, LB Constine, LS AF Earle, Craig C. Travis, Lois B. Constine, Louis S. BE Rubin, P Constine, LS Marks, LB TI Prologue: Surviving Cancer: SEER Statistics SO ALERT - ADVERSE LATE EFFECTS OF CANCER TREATMENT, VOL 1: GENERAL CONCEPTS AND SPECIFIC PRECEPTS SE Medical Radiology Diagnostic Imaging LA English DT Editorial Material; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; ROUTINE FOLLOW-UP; BREAST-CANCER; PRIMARY-CARE; GENERAL-PRACTICE; SPECIALIST CARE AB The number of cancer survivors is increasing rapidly because of a combination of demographic forces, public health success, and improving medical treatments. Projections are that the oncology workforce will be unable to meet the demand for cancer care in coming decades. Survivorship care planning can improve the quality of care and open up the possibility for survivorship care to be delivered by an array of health care providers. C1 [Earle, Craig C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Travis, Lois B.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Constine, Louis S.] Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM craig_earle@dfci.harvard.edu NR 16 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0942-5373 BN 978-3-540-72313-4; 978-3-540-72314-1 J9 MED RADIOL DIAGN IMA PY 2014 BP 1 EP 7 DI 10.1007/978-3-540-72314-1_1 D2 10.1007/978-3-540-72314-1 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BA2AA UT WOS:000333208500004 ER PT S AU Coleman, CN Hafer, N Maidment, B Manning, R Prasanna, P Okunieff, P AF Coleman, C. Norman Hafer, Nathaniel Maidment, Bert Manning, Ronald Prasanna, Pat Okunieff, Paul BE Rubin, P Constine, LS Marks, LB TI Radiological and Nuclear Terrorism: Relevance to the Radiation Oncology and Biology Communities SO ALERT - ADVERSE LATE EFFECTS OF CANCER TREATMENT, VOL 1: GENERAL CONCEPTS AND SPECIFIC PRECEPTS SE Medical Radiology Diagnostic Imaging LA English DT Article; Book Chapter ID ATOMIC-BOMB SURVIVORS; SOLID CANCER INCIDENCE; MEDICAL COUNTERMEASURES; DOSE ASSESSMENT; BIODOSIMETRY APPLICATIONS; NONHUMAN PRIMATE; SUPPORTIVE CARE; COMBINED INJURY; WORKSHOP; HEALTH AB There are now unique opportunities for research and community service for radiation experts based on a confluence of needs for reducing radiation toxicity for cancer care and preparing a medical response to a potential nuclear or radiological incident. The new opportunities include: (a) the need for agents (e.g., drugs, biologics, and natural products) to prevent and/or mitigate radiation injury; (b) the discovery and validation of biomarkers to predict radiation susceptibility and provide diagnostics for measuring dose (biodosimetry) and guiding clinical care; (c) basic research on mechanisms of radiation injury that are in common with other fields, such as inflammation, regenerative medicine, cancer, and aging; and (d) radiation biology research on mechanisms of radiation injury at the molecular, cellular, and organismal levels. The radiological/nuclear medical preparedness and response field is moving rapidly with a multipronged goal of ever-improving medical preparedness and response. This effort involves basic and translational science, device and medical countermeasure development, deployment of personnel and medical resources, access to up-to-date, just-in-time information for medical management, post-event recovery and resilience, and complex policy issues. The breadth of challenges provides an opportunity for a wide range of experts to participate. This chapter highlights the current state of the radiological/nuclear medical preparedness and response field. Given the rapidity with which research, development, and system solutions are evolving, this chapter emphasizes where to find up-to-date information. C1 [Coleman, C. Norman] US Dept HHS, Off Assistant Secretary Preparedness & Response A, Washington, DC 20201 USA. [Coleman, C. Norman; Prasanna, Pat] NCI, DCTD, RRP, Bethesda, MD 20892 USA. [Hafer, Nathaniel; Maidment, Bert] NIAID, NIH, Bethesda, MD 20892 USA. [Hafer, Nathaniel] Amer Assoc Advancement Sci, Washington, DC USA. [Manning, Ronald] BARDA, ASPR, Washington, DC USA. [Okunieff, Paul] Univ Florida, Shands Canc Ctr, Dept Radiat Oncol, Gainesville, FL USA. RP Coleman, CN (reprint author), US Dept HHS, Off Assistant Secretary Preparedness & Response A, Washington, DC 20201 USA. EM ccoleman@mail.nih.gov OI Hafer, Nathaniel/0000-0002-0164-5092 NR 72 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0942-5373 BN 978-3-540-72313-4; 978-3-540-72314-1 J9 MED RADIOL DIAGN IMA PY 2014 BP 293 EP 311 DI 10.1007/978-3-540-72314-1_20 D2 10.1007/978-3-540-72314-1 PG 19 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BA2AA UT WOS:000333208500023 ER PT J AU Conde-Agudelo, A Diaz-Rossello, JL AF Conde-Agudelo, Agustin Diaz-Rossello, Jose L. TI Kangaroo mother care to reduce morbidity and mortality in low birthweight infants SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review DE Infant Mortality; Infant, Low Birth Weight [growth & development]; Infant Care [methods]; Infant, Newborn; Infant, Premature, Diseases [prevention & control]; Length of Stay; Physical Stimulation [methods]; Randomized Controlled Trials as Topic; Weight Gain; Humans ID SKIN-TO-SKIN; RANDOMIZED CONTROLLED-TRIAL; CONVENTIONAL INCUBATOR CARE; PRETERM INFANTS; TRADITIONAL CARE; UTTAR-PRADESH; CONTACT; GROWTH; OUTCOMES; ATTACHMENT AB Background Kangaroo mother care (KMC), originally defined as skin-to-skin contact between a mother and her newborn, frequent and exclusive or nearly exclusive breastfeeding, and early discharge from hospital, has been proposed as an alternative to conventional neonatal care for low birthweight (LBW) infants. Objectives To determine whether there is evidence to support the use of KMC in LBW infants as an alternative to conventional neonatal care. Search methods The standard search strategy of the Cochrane Neonatal Group was used. This included searches in MEDLINE, EMBASE, LILACS, POPLINE, CINAHL databases (all from inception to March 31, 2014) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2014) In addition, we searched the web page of the Kangaroo Foundation, conference and symposia proceedings on KMC, and Google scholar. Selection criteria Randomized controlled trials comparing KMC versus conventional neonatal care, or early onset KMC (starting within 24 hours after birth) versus late onset KMC (starting after 24 hours after birth) in LBW infants. Data collection and analysis Data collection and analysis were performed according to the methods of the Cochrane Neonatal Review Group. Main results Eighteen studies, including 2751 infants, fulfilled inclusion criteria. Sixteen studies evaluated KMC in LBW infants after stabilization, one evaluated KMC in LBW infants before stabilization, and one compared early onset KMC with late onset KMC in relatively stable LBW infants. Thirteen studies evaluated intermittent KMC and five evaluated continuous KMC. At discharge or 40-41 weeks' postmenstrual age, KMC was associated with a reduction in the risk of mortality (typical risk ratio (RR) 0.60, 95% confidence interval (CI) 0.39 to 0.92; eight trials, 1736 infants), nosocomial infection/sepsis (typical RR 0.45, 95% CI 0.27 to 0.76), hypothermia (typical RR 0.34, 95% CI 0.17 to 0.67), and length of hospital stay (typical mean difference 2.2 days, 95% CI 0.6 to 3.7). At latest follow up, KMC was associated with a decreased risk of mortality (typical RR 0.67, 95% CI 0.48 to 0.95; 11 trials, 2167 infants) and severe infection/sepsis (typical RR 0.56, 95% CI 0.40 to 0.78). Moreover, KMC was found to increase some measures of infant growth, breastfeeding, and mother-infant attachment. There were no significant differences between KMC infants and controls in neurodevelopmental and neurosensory impairment at one year of corrected age. Sensitivity analysis suggested that the inclusion of studies with high risk of bias did not affect the general direction of findings or the size of the treatment effect for the main outcomes. Authors' conclusions The evidence from this updated review supports the use of KMC in LBW infants as an alternative to conventional neonatal care mainly in resource-limited settings. Further information is required concerning effectiveness and safety of early onset continuous KMC in unstabilized or relatively stabilized LBW infants, long term neurodevelopmental outcomes, and costs of care. C1 [Conde-Agudelo, Agustin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI 48202 USA. [Diaz-Rossello, Jose L.] United Nations Populat Fund UNFPA, Montevideo, Uruguay. RP Conde-Agudelo, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI 48202 USA. EM condeagu@hotmail.com FU Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health/Department of Health and Human Services, Bethesda, MD, USA; Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health/Department of Health and Human Services, Detroit, MI, USA; Department of Neonatology, University Hospital, Montevideo, Uruguay FX Internal sources; (AC-A) Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health/Department of Health and Human Services, Bethesda, MD and Detroit, MI, USA.; (JLD-R) Department of Neonatology, University Hospital, Montevideo, Uruguay. NR 82 TC 23 Z9 23 U1 7 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2014 IS 4 AR CD002771 DI 10.1002/14651858.CD002771.pub3 PG 137 WC Medicine, General & Internal SC General & Internal Medicine GA AH1MN UT WOS:000335885000006 PM 24752403 ER PT J AU Kethireddy, SR Tchounwou, PB Ahmad, HA Yerramilli, A Young, JH AF Kethireddy, Swatantra R. Tchounwou, Paul B. Ahmad, Hafiz A. Yerramilli, Anjaneyulu Young, John H. TI Geospatial Interpolation and Mapping of Tropospheric Ozone Pollution Using Geostatistics SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE tropospheric ozone (O-3); geostatistical analysis; prediction; interpolation; spatial resolution; visualization; Geographical Information Systems (GIS) ID AIR-QUALITY; HOUSTON; REGION; TEXAS; MODEL AB Tropospheric ozone (O-3) pollution is a major problem worldwide, including in the United States of America (USA), particularly during the summer months. Ozone oxidative capacity and its impact on human health have attracted the attention of the scientific community. In the USA, sparse spatial observations for O-3 may not provide a reliable source of data over a geo-environmental region. Geostatistical Analyst in ArcGIS has the capability to interpolate values in unmonitored geo-spaces of interest. In this study of eastern Texas O-3 pollution, hourly episodes for spring and summer 2012 were selectively identified. To visualize the O-3 distribution, geostatistical techniques were employed in ArcMap. Using ordinary Kriging, geostatistical layers of O-3 for all the studied hours were predicted and mapped at a spatial resolution of 1 kilometer. A decent level of prediction accuracy was achieved and was confirmed from cross-validation results. The mean prediction error was close to 0, the root mean-standardized-prediction error was close to 1, and the root mean square and average standard errors were small. O-3 pollution map data can be further used in analysis and modeling studies. Kriging results and O-3 decadal trends indicate that the populace in Houston-Sugar Land-Baytown, Dallas-Fort Worth-Arlington, Beaumont-Port Arthur, San Antonio, and Longview are repeatedly exposed to high levels of O-3-related pollution, and are prone to the corresponding respiratory and cardiovascular health effects. Optimization of the monitoring network proves to be an added advantage for the accurate prediction of exposure levels. C1 [Kethireddy, Swatantra R.; Yerramilli, Anjaneyulu; Young, John H.] Jackson State Univ, Trent Lott Geospatial & Visualizat Res Ctr, Coll Sci Engn & Technol, Mississippi E Ctr, Jackson, MS 39204 USA. [Tchounwou, Paul B.] Jackson State Univ, NIH RCMI Ctr Environm Hlth, Jackson, MS 39217 USA. [Ahmad, Hafiz A.] Jackson State Univ, Dept Biol, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, NIH RCMI Ctr Environm Hlth, 1400 JR Lynch St,POB 18750, Jackson, MS 39217 USA. EM swatantra.r.kethireddy@students.jsums.edu; paul.b.tchounwou@jsums.edu; hafiz.a.ahmad@jsums.edu; anjaneyulu.yerramilli@jsums.edu; john.h.young@jsums.edu FU National Institutes of Health [2G12RR013459]; NIH-NIMHD [8G12MD007581]; U.S. Department of Education Title III Historically Black Graduate Institutions at Jackson State University (JSU) [P031B90210-12] FX This research was made possible in part by a grant from the National Institutes of Health (Grant No. 2G12RR013459, and NIH-NIMHD Grant No. 8G12MD007581) and in part by a grant from the U.S. Department of Education Title III Historically Black Graduate Institutions (Grant No. P031B90210-12) at Jackson State University (JSU). We thank the Texas Air Monitoring Information System for providing pollutant and geospatial data. We thank Debra Sue Pate, Psychology Department, Jackson State University for her assistance. We would like to also extend gratitude to Samuel Jones Jr., university physician at JSU for his contribution to this project. NR 31 TC 2 Z9 2 U1 0 U2 26 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD JAN PY 2014 VL 11 IS 1 BP 983 EP 1000 DI 10.3390/ijerph110100983 PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA AB0BI UT WOS:000331456400054 PM 24434594 ER PT J AU Tchounwou, PB AF Tchounwou, Paul B. TI Ninth International Symposium on Recent Advances in Environmental Health Research SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Editorial Material C1 Jackson State Univ, NIH, RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, NIH, RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, 1400 Lynch St,Box 18750, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU NCRR NIH HHS [5G12RR013459-15, G12 RR013459]; NIMHD NIH HHS [G12 MD007581, 1G12MD007581-15]; PHS HHS [HHSN27621000644P] NR 4 TC 3 Z9 3 U1 0 U2 0 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD JAN PY 2014 VL 11 IS 1 BP 1001 EP 1004 DI 10.3390/ijerph110101001 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA AB0BI UT WOS:000331456400055 PM 24434595 ER PT J AU Abdelmegeed, MA Song, BJ AF Abdelmegeed, Mohamed A. Song, Byoung-Joon TI Functional Roles of Protein Nitration in Acute and Chronic Liver Diseases SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Review ID NONALCOHOLIC FATTY LIVER; NITRIC-OXIDE SYNTHASE; INDUCED MITOCHONDRIAL DYSFUNCTION; NITROTYROSINE-CONTAINING PEPTIDES; PEROXYNITRITE-MEDIATED NITRATION; MANGANESE SUPEROXIDE-DISMUTASE; HEPATIC CYTOCHROME-P450 2E1; INDUCED TYROSINE NITRATION; GLUTATHIONE-S-TRANSFERASE; TRANSGENIC MOUSE MODEL AB Nitric oxide, when combined with superoxide, produces peroxynitrite, which is known to be an important mediator for a number of diseases including various liver diseases. Peroxynitrite can modify tyrosine residue(s) of many proteins resulting in protein nitration, whichmay alter structure and function of each target protein. Various proteomics and immunological methods including mass spectrometry combined with both high pressure liquid chromatography and 2D PAGE have been employed to identify and characterize nitrated proteins from pathological tissue samples to determine their roles. However, these methods contain a few technical problems such as low efficiencies with the detection of a limited number of nitrated proteins and labor intensiveness. Therefore, a systematic approach to efficiently identify nitrated proteins and characterize their functional roles is likely to shed new insights into understanding of the mechanisms of hepatic disease pathophysiology and subsequent development of new therapeutics. The aims of this review are to briefly describe the mechanisms of hepatic diseases. In addition, we specifically describe a systematic approach to efficiently identify nitrated proteins to study their causal roles or functional consequences in promoting acute and chronic liver diseases including alcoholic and nonalcoholic fatty liver diseases. We finally discuss translational research applications by analyzing nitrated proteins in evaluating the efficacies of potentially beneficial agents to prevent or treat various diseases in the liver and other tissues. C1 [Abdelmegeed, Mohamed A.; Song, Byoung-Joon] NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. RP Abdelmegeed, MA (reprint author), NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM abdelmegeedm@mail.nih.gov; bj.song@nih.gov FU Intramural Program Fund at the National Institute on Alcohol Abuse and Alcoholism FX This research was supported by the Intramural Program Fund at the National Institute on Alcohol Abuse and Alcoholism. The authors thank Dr. Klaus Gawrisch for his support. NR 218 TC 0 Z9 1 U1 0 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1942-0900 EI 1942-0994 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2014 AR 149627 DI 10.1155/2014/149627 PG 21 WC Cell Biology SC Cell Biology GA AG9JG UT WOS:000335734800001 ER PT J AU Yamashita, CM Fessler, MB Vasanthamohan, L Lac, J Madenspacher, J McCaig, L Yao, LJ Wang, LF Puntorieri, V Mehta, S Lewis, JF Veldhuizen, RAW AF Yamashita, Cory M. Fessler, Michael B. Vasanthamohan, Lakshman Lac, Joanne Madenspacher, Jennifer McCaig, Lynda Yao, Lijuan Wang, Lefeng Puntorieri, Valeria Mehta, Sanjay Lewis, Jim F. Veldhuizen, Ruud A. W. TI Apolipoprotein E-Deficient Mice Are Susceptible to the Development of Acute Lung Injury SO RESPIRATION LA English DT Article DE Apolipoprotein E; Acute lung injury; Acid aspiration; Hyperoxia; Oxidized low-density lipoprotein; Gastric acid aspiration ID RESPIRATORY-DISTRESS-SYNDROME; LOW-DENSITY-LIPOPROTEIN; KNOCKOUT MICE; INFLAMMATORY MEDIATORS; ALVEOLAR MACROPHAGES; ENDOTHELIAL-CELLS; GENE-EXPRESSION; NADPH OXIDASE; OXIDIZED LDL; TNF-ALPHA AB Background: Apolipoprotein E (apoE) has been shown to play a pivotal role in the development of cardiovascular disease, attributable to its function in lipid trafficking and immune modulating properties; however, its role in modulating inflammation in the setting of acute lung injury (ALI) is unknown. Objective: To determine whether apoE-deficient mice (apoE-/-) are more susceptible to ALI compared to wild-type (WT) animals. Methods: Two independent models of ALI were employed. Firstly, WT and apoE-/- mice were randomized to acid aspiration (50 mu l of 0.1 N hydrochloric acid) followed by 4 h of mechanical ventilation. Secondly, WT and apoE-/- mice were randomized to 72 h of hyperoxia exposure or room air. Thereafter, the intrinsic responses of WT and apoE-/- mice were assessed using the isolated perfused mouse lung (IPML) setup. Finally, based on elevated levels of oxidized low-density lipoprotein (oxLDL) in apoE-/-, the effect of oxLDL on lung endothelial permeability and inflammation was assessed. Results: In both in vivo models, apoE-/- mice demonstrated greater increases in lung lavage protein levels, neutrophil counts, and cytokine expression (p < 0.05) compared to WT mice. Experiments utilizing the IPML setup demonstrated no differences in intrinsic lung responses to injury between apoE-/- and WT mice, suggesting the presence of a circulating factor as being responsible for the in vivo observations. Finally, the exposure of lung endothelial cells to oxLDL resulted in increased monolayer permeability and IL-6 release compared to native (nonoxidized) LDL. Conclusions: Our findings demonstrate a susceptibility of apoE-/- animals to ALI that may occur, in part, due to elevated levels of oxLDL. (C) 2014 S. Karger AG, Basel C1 [Yamashita, Cory M.; Vasanthamohan, Lakshman; Lac, Joanne; Madenspacher, Jennifer; McCaig, Lynda; Yao, Lijuan; Wang, Lefeng; Puntorieri, Valeria; Mehta, Sanjay; Lewis, Jim F.; Veldhuizen, Ruud A. W.] Lawson Hlth Res Inst, London, ON, Canada. [Fessler, Michael B.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. RP Yamashita, CM (reprint author), St Josephs Hlth Ctr, Lawson Hlth Res Inst, Room B3-116, London, ON N6H 4B2, Canada. EM cyamash@uwo.ca FU Ontario Thoracic Society/Ontario Lung Association; Western University Department of Medicine, Program of Experimental Medicine; National Institutes of Health NIEHS [Z01 ES102005] FX The authors would like to thank Ms. Shannon Seney of the Screening Lab for Immune Disorders, Lawson Health Research Institute, for her assistance with the multiplex analysis. This research was supported by the Ontario Thoracic Society/Ontario Lung Association (C.Y., J.F.L., and R. A. W. V.), the Western University Department of Medicine, Program of Experimental Medicine (C.Y.), and the Intramural Research Program of the National Institutes of Health NIEHS (Z01 ES102005) (M.B.F.). NR 36 TC 4 Z9 4 U1 0 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0025-7931 EI 1423-0356 J9 RESPIRATION JI Respiration PY 2014 VL 87 IS 5 BP 416 EP 427 DI 10.1159/000358438 PG 12 WC Respiratory System SC Respiratory System GA AH1YF UT WOS:000335917000010 PM 24662316 ER PT S AU Robey, PG Kuznetsov, SA Riminucci, M Bianco, P AF Robey, Pamela Gehron Kuznetsov, Sergei A. Riminucci, Mara Bianco, Paolo BE Hilton, MJ TI Bone Marrow Stromal Cell Assays: In Vitro and In Vivo SO SKELETAL DEVELOPMENT AND REPAIR: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Bone marrow; Colony-forming unit fibroblast; Bone; Cartilage; Stroma; Marrow adipocytes; In vitro assays; In vivo transplantation ID MESENCHYMAL STEM-CELLS; FIBROBLASTS; MOUSE AB Populations of bone marrow stromal cells (BMSCs, also known as bone marrow-derived "mesenchymal stem cells") contain a subset of cells that are able to recapitulate the formation of a bone/marrow organ (skeletal stem cells, SSCs). The biological properties of BMSC cultures are assessed by a variety of assays, both in vitro and in vivo. Application of these assays in an appropriate fashion provides a great deal of information on the role of BMSCs, and the subset of SSCs, in health and in disease. C1 [Robey, Pamela Gehron; Kuznetsov, Sergei A.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. [Riminucci, Mara; Bianco, Paolo] Univ Roma La Sapienza, I-00185 Rome, Italy. RP Robey, PG (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Intramural NIH HHS [Z01 DE000380-25] NR 18 TC 10 Z9 10 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-988-8; 978-1-62703-989-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1130 BP 279 EP 293 DI 10.1007/978-1-62703-989-5_21 D2 10.1007/978-1-62703-989-5 PG 15 WC Biochemistry & Molecular Biology; Cell & Tissue Engineering SC Biochemistry & Molecular Biology; Cell Biology GA BA1SC UT WOS:000333037600022 PM 24482181 ER PT J AU Xhaard, C Ren, Y Clero, E Maillard, S Brindel, P Rachedi, F Boissin, JL Sebbag, J Shan, L Bost-Bezeaud, F Petitdidier, P Drozdovitch, V Doyon, F Rubino, C de Vathaire, F AF Xhaard, Constance Ren, Yan Clero, Enora Maillard, Stephane Brindel, Pauline Rachedi, Frederique Boissin, Jean-Louis Sebbag, Joseph Shan, Larrys Bost-Bezeaud, Frederique Petitdidier, Patrick Drozdovitch, Vladimir Doyon, Francoise Rubino, Carole de Vathaire, Florent TI Differentiated Thyroid Carcinoma Risk Factors in French Polynesia SO ASIAN PACIFIC JOURNAL OF CANCER PREVENTION LA English DT Article DE Differentiated thyroid carcinoma; nuclear test; French Polynesia; radiation induced cancer ID POOLED ANALYSIS; CANCER RISK; ANTHROPOMETRIC FACTORS; REPRODUCTIVE FACTORS; ALCOHOL-CONSUMPTION; BODY-SIZE; WOMEN; POPULATION; SHANGHAI; SMOKING AB To investigate differentiated thyroid cancer risk factors in natives of French Polynesia is of interest because of the very high incidence of this cancer in the archipelago. Materials and Methods: To assess the role of various potential risk factors of thyroid cancer in the natives of French Polynesia we performed a case-control study. The study included almost all the French Polynesians diagnosed with differentiated thyroid carcinoma between 1981 and 2003 (n=229) and 373 French Polynesian control individuals from the general population without cancer. Results: Thyroid radiation dose received from nuclear fallout before the age of 15, a personal history of neck or/and head medical irradiation, obesity, tallness, large number of children, an artificial menopause, a familial history of thyroid cancer, a low dietary iodine intake, and having a spring as the main source of drinking water were found to be significant risk factors. No roles of smoking habits, alcohol consumption, iodine containing drugs, and exposure to pesticides were evidenced. Conclusions: Except for smoking, differentiated thyroid carcinoma risk factors in natives of French Polynesia are similar to those in other populations. Our finding on the role of having a spring as a drinking water origin is coherent with some other studies and could be due to geological factors. C1 [Xhaard, Constance; Ren, Yan; Clero, Enora; Maillard, Stephane; Brindel, Pauline; Doyon, Francoise; Rubino, Carole; de Vathaire, Florent] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, U1018, Radiat Epidemiol Grp, Villejuif, France. [Xhaard, Constance; Ren, Yan; Clero, Enora; Maillard, Stephane; Brindel, Pauline; Doyon, Francoise; Rubino, Carole; de Vathaire, Florent] Gustave Roussy, Villejuif, France. [Xhaard, Constance; Ren, Yan; Clero, Enora; Maillard, Stephane; Brindel, Pauline; Doyon, Francoise; Rubino, Carole; de Vathaire, Florent] Univ Paris 11, Villejuif, France. [Drozdovitch, Vladimir] Int Agcy Res Canc, F-69372 Lyon, France. [Rachedi, Frederique; Bost-Bezeaud, Frederique] Terr Hosp Taaone, Papeete, Fr Polynesia. [Petitdidier, Patrick] Lab Boz, Papeete, Fr Polynesia. [Drozdovitch, Vladimir] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP de Vathaire, F (reprint author), INSERM, Ctr Res Epidemiol & Populat Hlth CESP, U1018, Radiat Epidemiol Grp, Villejuif, France. EM florent.devathaire@gustaveroussy.fr RI de Vathaire, Florent/L-2983-2016 FU Association pour la Recherche contre le Cancer; Ligue Nationale Contre le Cancer,; Direction Generale de la Sante; Comite de radioprotection de Electricite de France,; Agence Francaise de Securite Sanitaire et Environnementale et du Travail; CHILD-THYR EEC programme FX This study was supported by the Association pour la Recherche contre le Cancer, the Ligue Nationale Contre le Cancer, the Direction Generale de la Sante, the Comite de radioprotection de Electricite de France, Agence Francaise de Securite Sanitaire et Environnementale et du Travail and CHILD-THYR EEC programme. The authors thank J Paaoafaite, J Teuri, J Iltis from the Institute of Research for Development (IRD) and Drs Ph Morales, P Giraud, P Didiergeorge, M Brisard, G Soubiran, A Merceron, ML Vanizette, P Dupire, M Berges, J Ienfa, G de Clermont, N Cerf, B Oddo, M Bambridge, C Baron, A Mouchard-Rachet, O Simonet, D Lamarque, A Vabret, J Delacre, MP Darquier, and J Leninger for their help. NR 44 TC 7 Z9 7 U1 2 U2 5 PU ASIAN PACIFIC ORGANIZATION CANCER PREVENTION PI GYEONGGI-DO PA APJCP HEAD OFFICE, KOREAN NATL CANCER CENTER, 323 ILAN -RO, ILSANDONG-GU, GOYANG-SI, GYEONGGI-DO, 410-769, SOUTH KOREA SN 1513-7368 J9 ASIAN PAC J CANCER P JI Asian Pac. J. Cancer Prev. PY 2014 VL 15 IS 6 BP 2675 EP 2680 DI 10.7314/APJCP.2014.15.6.2675 PG 6 WC Oncology SC Oncology GA AG8EN UT WOS:000335651700044 PM 24761883 ER PT J AU Ricardo, AC Yang, W Lora, CM Gordon, EJ Diamantidis, CJ Ford, V Kusek, JW Lopez, A Lustigova, E Nessel, L Rosas, SE Steigerwalt, S Theurer, J Zhang, XM Fischer, MJ Lash, JP Investigators, C AF Ricardo, Ana C. Yang, Wei Lora, Claudia M. Gordon, Elisa J. Diamantidis, Clarissa J. Ford, Virginia Kusek, John W. Lopez, Amada Lustigova, Eva Nessel, Lisa Rosas, Sylvia E. Steigerwalt, Susan Theurer, Jacqueline Zhang, Xiaoming Fischer, Michael J. Lash, James P. Investigators, C. R. I. C. TI Limited health literacy is associated with low glomerular filtration in the Chronic Renal Insufficiency Cohort (CRIC) study SO CLINICAL NEPHROLOGY LA English DT Article DE chronic kidney disease; health literacy ID CHRONIC KIDNEY-DISEASE; MANAGED CARE ENROLLEES; DIALYSIS PATIENTS; SELF-MANAGEMENT; KNOWLEDGE; PREVALENCE; MORTALITY; OUTCOMES; RISK; LINE AB Background: Low health literacy in the general population is associated with increased risk of death and hospitalization. The evaluation of health literacy in individuals with predialysis chronic kidney disease (CKD) is limited. Methods: We conducted a cross-sectional study to evaluate the associations of limited health literacy with kidney function and cardiovascular disease (CVD) risk factors in 2,340 non-Hispanic (NH) Whites and Blacks aged 21 - 74 years with mild-to-moderate CKD. Limited health literacy was defined as a Short Test of Functional Health Literacy in Adults (STOFHLA) score <= 22. Outcomes evaluated included estimated glomerular filtration rate (eGFR), 24-hour urine protein excretion, and CVD risk factors. Results: The prevalence of limited health literacy was 28% in NH-Blacks and 5% in NH-Whites. Compared with participants with adequate health literacy, those with limited health literacy were more likely to have lower eGFR (34 vs. 42 mL/min/1.73 m(2)); higher urine protein/24-hours (0.31 vs. 0.15 g); and higher self-reported CVD (61 vs. 37%); and were less likely to have BP < 130/80 mmHg (51 vs. 58%); p <= 0.01 for each comparison. After adjustment, limited health literacy was associated with self-reported CVD (OR 1.51, 95% CI 1.13 - 2.03) and lower eGFR (beta -2.47, p = 0.03). Conclusion: In this CKD cohort, limited health literacy was highly prevalent, especially among NH-Blacks, and it was associated with lower eGFR and a less favorable CVD risk factor profile. Further studies are needed to better understand these associations and inform the development of health literacy interventions among individuals with CKD. C1 [Ricardo, Ana C.; Lora, Claudia M.; Lopez, Amada; Fischer, Michael J.; Lash, James P.] Univ Illinois, Dept Med, Chicago, IL 60616 USA. [Yang, Wei; Ford, Virginia; Nessel, Lisa; Zhang, Xiaoming] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Gordon, Elisa J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Diamantidis, Clarissa J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Kusek, John W.] NIDDK, NIH, Bethesda, MD 20892 USA. [Lustigova, Eva] Tulane Univ, New Orleans, LA 70118 USA. [Rosas, Sylvia E.] Univ Penn, Philadelphia VA Med Ctr, Dept Med, Philadelphia, PA 19104 USA. [Steigerwalt, Susan] St Johns Hlth Syst, Detroit, MI USA. [Theurer, Jacqueline] MetroHlth Med Ctr, Dept Med, Div Nephrol, Cleveland, OH USA. [Fischer, Michael J.] Jesse Brown VA Med Ctr, Ctr Management Complex Chron Care, Chicago, IL USA. RP Ricardo, AC (reprint author), Univ Illinois, Nephrol Sect, 820 South Wood St,Room 470, Chicago, IL 60616 USA. EM aricar2@uic.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, 5U01DK060902]; HCRIC [R01 DK072231]; institutional Clinical Translational Science Awards (CTSA); National Institutes of Health (NIH) [UL1 RR-025005, GRCR M01 RR-16500, UL1 RR-024989, GCRC M01 RR-000042, CTSA UL1 RR-024986, M01 RR-013987-06, RR-05096, UCSF-CTSI UL1 RR-024131, 5K24DK002651]; National Center for Minority Health and Health Disparities, NIH; Department of Veterans Affairs Health Services Research and Development Service (MJF Career Development Award) FX This work was funded under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, 5U01DK060902) and an R01 DK072231 (HCRIC). In addition, this work was supported in part by institutional Clinical Translational Science Awards (CTSA) and other National Institutes of Health (NIH) grants: Johns Hopkins University UL1 RR-025005; University of Maryland GRCR M01 RR-16500; Case Western Reserve University Clinical and Translational Science Collaborative (University Hospitals of Cleveland, Cleveland Clinic Foundation, and MetroHealth) UL1 RR-024989; University of Michigan GCRC M01 RR-000042, CTSA UL1 RR-024986; University of Illinois at Chicago Clinical Research Center, M01 RR-013987-06; Tulane/LSU/Charity Hospital General Clinical Research Center RR-05096; University of Pennsylvania CTSA UL1 RR-024134; Kaiser NIH/NCRR UCSF-CTSI UL1 RR-024131, 5K24DK002651. Additional support was provided by the National Center for Minority Health and Health Disparities, NIH, and Department of Veterans Affairs Health Services Research and Development Service (MJF Career Development Award). NR 38 TC 11 Z9 12 U1 5 U2 12 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD JAN PY 2014 VL 81 IS 1 BP 30 EP 37 DI 10.5414/CN108062 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AG5FL UT WOS:000335444800004 PM 24219913 ER PT J AU Ried, T AF Ried, Thomas BE Gelmann, EP Sawyers, CL Rauscher, FJ TI Chromosome analysis: molecular cytogenetic approaches SO MOLECULAR ONCOLOGY: CAUSES OF CANCER AND TARGETS FOR TREATMENT LA English DT Article; Book Chapter ID IN-SITU HYBRIDIZATION; COMPARATIVE GENOMIC HYBRIDIZATION; TELOMERASE GENE TERC; INSITU HYBRIDIZATION; LUNG-CANCER; HEMATOLOGIC MALIGNANCIES; CYTOLOGICAL PREPARATIONS; MOUSE CHROMOSOMES; EPITHELIAL-CELLS; BURKITT-LYMPHOMA C1 NCI, Sect Canc Genom, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Ried, T (reprint author), NCI, Sect Canc Genom, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NR 60 TC 0 Z9 0 U1 0 U2 0 PU PRINCETON UNIV PRESS PI PRINCETON PA 41 WILLIAM ST, PRINCETON, NJ 08540 USA BN 978-0-521-87662-9 PY 2014 BP 28 EP 36 PG 9 WC Oncology SC Oncology GA BA1DD UT WOS:000332401400005 ER PT J AU Cecchi, F Lee, YH Bottaro, DP AF Cecchi, Fabiola Lee, Young H. Bottaro, Donald P. BE Gelmann, EP Sawyers, CL Rauscher, FJ TI Hepatocyte growth factor/Met signaling in cancer SO MOLECULAR ONCOLOGY: CAUSES OF CANCER AND TARGETS FOR TREATMENT LA English DT Article; Book Chapter ID RECEPTOR TYROSINE KINASE; CELL LUNG-CANCER; C-MET; INVASIVE GROWTH; THERAPEUTIC INHIBITION; FACTOR/SCATTER FACTOR; GEFITINIB RESISTANCE; ANAPLASTIC LYMPHOMA; SELECTIVE INHIBITOR; ANTITUMOR-ACTIVITY C1 [Cecchi, Fabiola; Lee, Young H.; Bottaro, Donald P.] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Cecchi, F (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 77 TC 0 Z9 0 U1 0 U2 0 PU PRINCETON UNIV PRESS PI PRINCETON PA 41 WILLIAM ST, PRINCETON, NJ 08540 USA BN 978-0-521-87662-9 PY 2014 BP 204 EP 217 PG 14 WC Oncology SC Oncology GA BA1DD UT WOS:000332401400018 ER PT J AU Ahn, B Stevnsner, T Bohr, VA AF Ahn, Byungchan Stevnsner, Tinna Bohr, Vilhelm A. BE Gelmann, EP Sawyers, CL Rauscher, FJ TI Werner syndrome: association of premature aging and cancer predisposition SO MOLECULAR ONCOLOGY: CAUSES OF CANCER AND TARGETS FOR TREATMENT LA English DT Article; Book Chapter ID STALLED REPLICATION FORKS; CULTURED SKIN FIBROBLASTS; SYNDROME PROTEIN FUNCTION; IMMORTALIZED HUMAN-CELLS; INTERSTRAND CROSS-LINKS; TOPOISOMERASE-I POISONS; WRN HELICASE ACTIVITY; DNA-POLYMERASE-DELTA; STRAND BREAK REPAIR; S-PHASE CHECKPOINT C1 [Ahn, Byungchan] Univ Ulsan, Dept Life Sci, Ulsan 680749, South Korea. [Stevnsner, Tinna] Univ Aarhus, Danish Ctr Mol Gerontol, Dept Mol Biol, DK-8000 Aarhus C, Denmark. [Stevnsner, Tinna] Univ Aarhus, Danish Aging Res Ctr, Dept Mol Biol, DK-8000 Aarhus C, Denmark. [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Ahn, B (reprint author), Univ Ulsan, Dept Life Sci, Ulsan 680749, South Korea. NR 126 TC 0 Z9 0 U1 0 U2 1 PU PRINCETON UNIV PRESS PI PRINCETON PA 41 WILLIAM ST, PRINCETON, NJ 08540 USA BN 978-0-521-87662-9 PY 2014 BP 423 EP 433 PG 11 WC Oncology SC Oncology GA BA1DD UT WOS:000332401400036 ER PT J AU Van Waes, C Bian, YS Allen, CT Morris, JC Chen, Z AF Van Waes, Carter Bian, Yansong Allen, Clint T. Morris, John C. Chen, Zhong BE Gelmann, EP Sawyers, CL Rauscher, FJ TI Squamous-cell carcinoma SO MOLECULAR ONCOLOGY: CAUSES OF CANCER AND TARGETS FOR TREATMENT LA English DT Article; Book Chapter ID GROWTH-FACTOR RECEPTOR; NF-KAPPA-B; TUMOR-SUPPRESSOR GENES; FANCONI-ANEMIA PATIENTS; NECK-CANCER; HUMAN-PAPILLOMAVIRUS; LUNG-CANCER; CLINICOPATHOLOGICAL FINDINGS; THERAPEUTIC TARGET; TYROSINE KINASE C1 [Van Waes, Carter; Allen, Clint T.; Chen, Zhong] NIDCD, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. [Bian, Yansong] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. [Morris, John C.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Van Waes, C (reprint author), NIDCD, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. NR 72 TC 0 Z9 0 U1 0 U2 2 PU PRINCETON UNIV PRESS PI PRINCETON PA 41 WILLIAM ST, PRINCETON, NJ 08540 USA BN 978-0-521-87662-9 PY 2014 BP 686 EP 692 PG 7 WC Oncology SC Oncology GA BA1DD UT WOS:000332401400062 ER PT J AU Helman, LJ AF Helman, Lee J. BE Gelmann, EP Sawyers, CL Rauscher, FJ TI Sarcomas SO MOLECULAR ONCOLOGY: CAUSES OF CANCER AND TARGETS FOR TREATMENT LA English DT Article; Book Chapter ID GASTROINTESTINAL STROMAL TUMORS; SOFT-TISSUE SARCOMAS; METASTATIC DERMATOFIBROSARCOMA PROTUBERANS; POLYMERASE CHAIN-REACTION; GROWTH-FACTOR-B; EWINGS-SARCOMA; ALVEOLAR RHABDOMYOSARCOMA; IMATINIB MESYLATE; EMBRYONAL RHABDOMYOSARCOMA; TRANSCRIPTION FACTORS C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Helman, LJ (reprint author), NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 61 TC 0 Z9 0 U1 0 U2 1 PU PRINCETON UNIV PRESS PI PRINCETON PA 41 WILLIAM ST, PRINCETON, NJ 08540 USA BN 978-0-521-87662-9 PY 2014 BP 731 EP 737 PG 7 WC Oncology SC Oncology GA BA1DD UT WOS:000332401400068 ER PT J AU Kuehl, WM Bergsagel, PL AF Kuehl, W. Michael Bergsagel, P. Leif BE Gelmann, EP Sawyers, CL Rauscher, FJ TI Multiple myeloma SO MOLECULAR ONCOLOGY: CAUSES OF CANCER AND TARGETS FOR TREATMENT LA English DT Article; Book Chapter ID CYCLIN-D DYSREGULATION; PLASMA-CELL TUMORS; BONE-MARROW; CHROMOSOME TRANSLOCATIONS; MOLECULAR PATHOGENESIS; GENETIC ABNORMALITIES; MONOCLONAL GAMMOPATHY; PROGNOSTIC VALUE; EXPRESSION; PROGRESSION C1 [Kuehl, W. Michael] NCI, Canc Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Bergsagel, P. Leif] Mayo Clin, Ctr Comprehens Canc, Div Hematol Oncol, Scottsdale, AZ USA. RP Kuehl, WM (reprint author), NCI, Canc Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 55 TC 0 Z9 0 U1 0 U2 0 PU PRINCETON UNIV PRESS PI PRINCETON PA 41 WILLIAM ST, PRINCETON, NJ 08540 USA BN 978-0-521-87662-9 PY 2014 BP 799 EP 808 PG 10 WC Oncology SC Oncology GA BA1DD UT WOS:000332401400075 ER PT J AU Fojo, AT AF Fojo, Antonio Tito BE Gelmann, EP Sawyers, CL Rauscher, FJ TI Drug resistance: as complex and diverse as the disease itself SO MOLECULAR ONCOLOGY: CAUSES OF CANCER AND TARGETS FOR TREATMENT LA English DT Article; Book Chapter ID CHRONIC MYELOID-LEUKEMIA; RENAL-CELL CARCINOMA; CHRONIC MYELOGENOUS LEUKEMIA; GASTROINTESTINAL STROMAL TUMORS; STANDARD-DOSE IMATINIB; CENTRAL-NERVOUS-SYSTEM; P-GLYCOPROTEIN ABCB1; BINDING CASSETTE ABC; PHASE-III TRIAL; MULTIDRUG-RESISTANCE C1 [Fojo, Antonio Tito] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Fojo, Antonio Tito] NCI, Expt Therapeut Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Fojo, AT (reprint author), NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NR 77 TC 0 Z9 0 U1 0 U2 0 PU PRINCETON UNIV PRESS PI PRINCETON PA 41 WILLIAM ST, PRINCETON, NJ 08540 USA BN 978-0-521-87662-9 PY 2014 BP 921 EP 928 PG 8 WC Oncology SC Oncology GA BA1DD UT WOS:000332401400089 ER PT J AU Sarker, MMH Zhou, MC Rameshwar, P Hanover, JA AF Sarker, Md. Mosharrof Hossain Zhou, MengChu Rameshwar, Pranela Hanover, John A. TI Functions and Roles of Proteins: Diabetes as a Paradigm SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review DE beta-Cells; Protein; Force-ratio; Stem cells ID BETA-CELL DEVELOPMENT; EMBRYONIC STEM-CELLS; THERAPY; BIOLOGY AB Molecular and cellular biology has moved towards complete and accurate knowledge of how molecules behave in space and time. Protein is considered as the primary group of molecules responsible for mediating most physiological processes. Changes in the levels of proteins may lead to the altered function and are responsible for many diseases. This review provides a partial molecular explanation of biological force-ratio generation that may act to split protein into branches, and shows molecular functional divergence. Developing a non-reductionist theory of the cellular function in medicine is clearly not sufficient. Finding effective parameters of the models by characterizing molecular interactions becomes necessary. Protein interactivity and stability provides a basis for an integrated understanding of pathologies such diabetes. One example of how a mechanistic analysis of such physiological processes can be of value is the time-delay between mRNA and translation that can act as a fork allowing a slowdown in gene expression. Published by Elsevier Ltd. C1 [Sarker, Md. Mosharrof Hossain; Zhou, MengChu] New Jersey Inst Technol, Dept Elect & Comp Engn, Newark, NJ 07102 USA. [Rameshwar, Pranela] Rutgers, New Jersey Med Sch, Grad Sch Biomed Sci, Dept Med Hematol Oncol, Newark, NJ 07103 USA. [Hanover, John A.] NIDDK, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Sarker, MMH (reprint author), New Jersey Inst Technol, Dept Elect & Comp Engn, Newark, NJ 07102 USA. EM mhs43@njit.edu; zhou@njit.edu; rameshwa@njms.rutgers.edu; jah@helix.nih.gov NR 18 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD JAN PY 2014 VL 114 IS 1 BP 2 EP 7 DI 10.1016/j.pbiomolbio.2013.11.003 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AG7SE UT WOS:000335617900002 PM 24239502 ER PT J AU Wint, DP Butman, JA Masdeu, JC Meyer-Lindenberg, A Mervis, CB Sarpal, D Morris, CA Berman, KF AF Wint, D. P. Butman, J. A. Masdeu, J. C. Meyer-Lindenberg, A. Mervis, C. B. Sarpal, D. Morris, C. A. Berman, K. F. TI Intracranial Arteries in Individuals with the Elastin Gene Hemideletion of Williams Syndrome SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID SUPRAVALVULAR AORTIC-STENOSIS; BEUREN-SYNDROME; CEREBRAL ARTERIOPATHY; ISCHEMIC-STROKE; INFARCTION; ADULT; CHILDREN AB BACKGROUND AND PURPOSE: Williams syndrome, a rare genetic disorder with a striking neurobehavioral profile characterized by extreme sociability and impaired visuospatial construction abilities, is caused by a hemideletion that includes the elastin gene, resulting in frequent supravavular aortic stenosis and other stenotic arterial lesions. Strokes have been reported in Williams syndrome. Although the extracranial carotid artery has been studied in a sample of patients with Williams syndrome, proximal intracranial arteries have not. MATERIALS AND METHODS: Using MRA, we studied the intracranial vessels in 27 participants: 14 patients with Williams syndrome (age range, 18-44 years; mean age, 27.3 9.1; 43% women) and 13 healthy control participants with similar age and sex distribution (age range, 22-52 years; mean age, 33.4 7.6; 46% women). All participants with Williams syndrome had hemideletions of the elastin gene. Blinded to group allocation or to any other clinical data, a neuroradiologist determined the presence of intracranial vascular changes in the 2 groups. RESULTS: The Williams syndrome group and the healthy control group had similar patency of the proximal intracranial arteries, including the internal carotid and vertebral arteries; basilar artery; and stem and proximal branches of the anterior cerebral artery, MCA, and posterior cerebral arteries. The postcommunicating segment of the anterior cerebral artery was longer in the Williams syndrome group. CONCLUSIONS: Despite the elastin haploinsufficiency, the proximal intracranial arteries in Williams syndrome preserve normal patency. C1 [Wint, D. P.; Masdeu, J. C.; Meyer-Lindenberg, A.; Sarpal, D.; Berman, K. F.] NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch, Bethesda, MD USA. [Butman, J. A.] NIH, Warren G Magnuson Clin Ctr, Intramural Res Program, Bethesda, MD 20892 USA. [Mervis, C. B.] Univ Louisville, Dept Psychol & Brain Sci, Neurodev Sci Lab, Louisville, KY 40292 USA. [Morris, C. A.] Univ Nevada, Sch Med, Dept Pediat, Las Vegas, NV 89154 USA. RP Berman, KF (reprint author), 10 Ctr Dr 3C111, Bethesda, MD 20892 USA. EM bermank@mail.nih.gov RI Sarpal, Deepak/O-5630-2014; Butman, John/J-2780-2013; OI Butman, John/0000-0002-1547-9195; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU NIMH Intramural Research Program, Bethesda, Maryland; National Institute of Neurological Disorders and Stroke [R01 NS35102] FX This work was funded by the NIMH Intramural Research Program, Bethesda, Maryland, and by a grant from the National Institute of Neurological Disorders and Stroke (R01 NS35102) to C. B. M. NR 36 TC 1 Z9 1 U1 0 U2 3 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JAN PY 2014 VL 35 IS 1 BP 90 EP 94 DI 10.3174/ajnr.A3641 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AD9ER UT WOS:000333568100018 PM 23868161 ER PT J AU Rodrigo, L Blanco, I Bobes, J de Serres, FJ AF Rodrigo, Luis Blanco, Ignacio Bobes, Julio de Serres, Frederick J. TI Response to 'Remarkable prevalence of celiac disease in patients with irritable bowel syndrome plus fibromyalgia in comparison with those with isolated irritable bowel syndrome: a case-finding study' - authors' reply SO ARTHRITIS RESEARCH & THERAPY LA English DT Letter C1 [Rodrigo, Luis] Cent Univ Hosp Asturias HUCA, Oviedo 33006, Principality Of, Spain. [Blanco, Ignacio] Biomed Res Off Principal Asturias FICYT, Oviedo 33009, Principality Of, Spain. [Bobes, Julio] Univ Oviedo, Dept Med, Psychiat Area, E-33006 Oviedo, Principality Of, Spain. [de Serres, Frederick J.] NIEHS, Chapel Hill, NC 27709 USA. RP Rodrigo, L (reprint author), Cent Univ Hosp Asturias HUCA, C Celestino Villamil SN, Oviedo 33006, Principality Of, Spain. EM lrodrigosaez@gmail.com NR 4 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2014 VL 16 IS 1 AR 403 DI 10.1186/ar4488 PG 2 WC Rheumatology SC Rheumatology GA AG1BA UT WOS:000335148700069 PM 24528551 ER PT J AU Pholphirul, P Kamlai, J AF Pholphirul, Piriya Kamlai, Jongkon TI How Much Do Low-skilled Immigrants Contribute to the Thai Economy?: Analysis of Three Methodologies SO ASIAN AND PACIFIC MIGRATION JOURNAL LA English DT Article ID LABOR-MARKET; SUBSTITUTION; ELASTICITIES; IMPACT AB This paper uses three methodologies to measure the economic impacts and contribution of low-skilled immigration in Thailand, namely, simulation of a macroeconomic model, a growth accounting method, and an econometric method. Both the macroeconomic simulation model and the growth accounting method confirm that immigrants have contributed around 0.75-1 percentage point of real GDP growth. The sector that benefited most was agriculture, where immigrant workers contributed more than 1.33 percent of the growth rate of agricultural production. Our econometric results also showed that a percentage increase of immigrant share (of the total labor force or M/L) also contributed to a reduction of overall labor productivity in the manufacturing sector (by about 0.88-1percent) and the service sector (by about 1.35 percent). In addition, the calculation of the Allen partial elasticity (AES) confirms that there is a high substitution effect between immigrants and natives, especially in the low-skilled sector. Our simulation shows that employing immigrants in the agricultural sector tends to reduce total employment by 0.67 percent and reduce wage rates by around 4.34 percent from the base case. Thailand needs to consider the short-term and long-term implications of bringing in immigrant labor. C1 [Pholphirul, Piriya] NIDA, Bethesda, MD 20892 USA. [Kamlai, Jongkon] Minist Finance, Bangkok, Thailand. RP Pholphirul, P (reprint author), NIDA, Bethesda, MD 20892 USA. NR 26 TC 0 Z9 0 U1 2 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0117-1968 EI 2057-049X J9 ASIAN PAC MIGR J JI Asian Pac. Migr. J. PY 2014 VL 23 IS 1 BP 85 EP 112 PG 28 WC Demography SC Demography GA AG0QW UT WOS:000335121700004 ER PT J AU Kitahara, CM Linet, MS Brenner, AV Wang, SS Melin, BS Wang, ZM Inskip, PD Freeman, LEB Braganza, MZ Carreon, T Feychting, M Gaziano, JM Peters, U Purdue, MP Ruder, AM Sesso, HD Shu, XO Waters, MA White, E Zheng, W Hoover, RN Fraumeni, JF Chatterjee, N Yeager, M Chanock, SJ Hartge, P Rajaraman, P AF Kitahara, Cari M. Linet, Martha S. Brenner, Alina V. Wang, Sophia S. Melin, Beatrice S. Wang, Zhaoming Inskip, Peter D. Freeman, Laura E. Beane Braganza, Melissa Z. Carreon, Tania Feychting, Maria Gaziano, J. Michael Peters, Ulrike Purdue, Mark P. Ruder, Avima M. Sesso, Howard D. Shu, Xiao-Ou Waters, Martha A. White, Emily Zheng, Wei Hoover, Robert N. Fraumeni, Joseph F., Jr. Chatterjee, Nilanjan Yeager, Meredith Chanock, Stephen J. Hartge, Patricia Rajaraman, Preetha TI Personal History of Diabetes, Genetic Susceptibility to Diabetes, and Risk of Brain Glioma: A Pooled Analysis of Observational Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; CENTRAL-NERVOUS-SYSTEM; INSULIN-RESISTANCE; PHYSICIANS HEALTH; CANCER INCIDENCE; TUMORS; VARIANTS; MELLITUS; COHORT; LOCI AB Background: Brain glioma is a relatively rare and fatal malignancy in adulthood with few known risk factors. Some observational studies have reported inverse associations between diabetes and subsequent glioma risk, but possible mechanisms are unclear. Methods: We conducted a pooled analysis of original data from five nested case-control studies and two case-control studies from the United States and China that included 962 glioma cases and 2,195 controls. We examined self-reported diabetes history in relation to glioma risk, as well as effect modification by seven glioma risk associated single-nucleotide polymorphisms(SNP). We also examined the associations between 13 diabetes risk associated SNPs, identified from genome-wide association studies, and glioma risk. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable-adjusted logistic regression models. Results: We observed a 42% reduced risk of glioma for individuals with a history of diabetes (OR = 0.58; 95% CI, 0.40-0.84). The association did not differ by sex, study design, or after restricting to glioblastoma, the most common histological subtype. We did not observe any significant per-allele trends among the 13 diabetes related SNPs examined in relation to glioma risk. Conclusion: These results support an inverse association between diabetes history and glioma risk. The role of genetic susceptibility to diabetes cannot be excluded, and should be pursued in future studies together with other factors that might be responsible for the diabetes-glioma association. Impact: These data suggest the need for studies that can evaluate, separately, the association between type 1 and type 2 diabetes and subsequent risk of adult glioma. Cancer Epidemiol Biomarkers Prev; 23(1); 47-54. (C) 2013 AACR. C1 [Kitahara, Cari M.; Linet, Martha S.; Brenner, Alina V.; Wang, Zhaoming; Inskip, Peter D.; Freeman, Laura E. Beane; Braganza, Melissa Z.; Purdue, Mark P.; Hoover, Robert N.; Fraumeni, Joseph F., Jr.; Chatterjee, Nilanjan; Yeager, Meredith; Chanock, Stephen J.; Hartge, Patricia; Rajaraman, Preetha] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Wang, Zhaoming; Yeager, Meredith; Chanock, Stephen J.] SAIC Frederick Inc, Core Genotyping Facil, NCI, Gaithersburg, MD USA. [Wang, Sophia S.] City Hope & Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA. [Carreon, Tania; Ruder, Avima M.; Waters, Martha A.] NIOSH, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA. [Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med, Boston, MA 02115 USA. [Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Brigham & Womens Hosp, Div Aging, Sch Med, Boston, MA 02115 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Res & Informat Ctr, Massachusetts Vet Epidemiol, Boston, MA USA. [Peters, Ulrike] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Peters, Ulrike; White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Melin, Beatrice S.] Umea Univ, Dept Radiat Sci, Umea, Sweden. [Feychting, Maria] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. RP Kitahara, CM (reprint author), Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7E-566, Bethesda, MD 20892 USA. EM meinholdc@mail.nih.gov RI Purdue, Mark/C-9228-2016; Kitahara, Cari/R-8267-2016 OI Purdue, Mark/0000-0003-1177-3108; FU National Institutes of Health [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595]; Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention; National Cancer Institute; NIH; DHHS; NIOSH operating funds; National Cancer Institute [K05CA154337]; NIH Office of Dietary Supplements FX The authors thank all investigators who contributed data for the GliomaScan study.; For PHS: The PHS is supported by grants CA 97193, CA 34944, CA 40360, HL 26490, and HL 34595 from the National Institutes of Health. For PLCO: This research was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS.; For NIOSH: This research was supported by NIOSH operating funds. The contributions of former laboratory director Mary Ann Butler are gratefully acknowledged. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the National Institute for Occupational Safety and Health.; For VITAL: Grant K05CA154337 is funded by the National Cancer Institute (NCI) and the NIH Office of Dietary Supplements (ODS). NR 37 TC 10 Z9 10 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2014 VL 23 IS 1 BP 47 EP 54 DI 10.1158/1055-9965.EPI-13-0913 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZB UT WOS:000335143400006 PM 24220915 ER PT J AU O'Brien, KM Cole, SR Engel, LS Bensen, JT Poole, C Herring, AH Millikan, RC AF O'Brien, Katie M. Cole, Stephen R. Engel, Lawrence S. Bensen, Jeannette T. Poole, Charles Herring, Amy H. Millikan, Robert C. TI Breast Cancer Subtypes and Previously Established Genetic Risk Factors: A Bayesian Approach SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; CARCINOMA IN-SITU; TRIPLE-NEGATIVE PHENOTYPE; LONG-TERM SURVIVAL; BASAL-LIKE SUBTYPE; SUSCEPTIBILITY LOCI; ESTROGEN-RECEPTOR; TUMOR SUBTYPES; AFRICAN-AMERICAN; POPULATION STRATIFICATION AB Background: Gene expression analyses indicate that breast cancer is a heterogeneous disease with at least five immunohistologic subtypes. Despite growing evidence that these subtypes are etiologically and prognostically distinct, few studies have investigated whether they have divergent genetic risk factors. To help fill in this gap in our understanding, we examined associations between breast cancer subtypes and previously established susceptibility loci among white and African-American womenin the Carolina Breast Cancer Study. Methods: We used Bayesian polytomous logistic regression to estimate ORs and 95% posterior intervals for the association between each of 78 single nucleotide polymorphisms (SNP) and five breast cancer subtypes. Subtypes were defined using five immunohistochemical markers: estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptors 1 and 2 (HER1/2), and cytokeratin (CK) 5/6. Results: Several SNPs in TNRC9/TOX3 were associated with luminal A (ER/PR+, HER2-) or basal-like breast cancer (ER-, PR-, HER2-, HER1, or CK 5/6+), and one SNP (rs3104746) was associated with both. SNPs in FGFR2 were associated with luminal A, luminal B (ER/PR+, HER2-), or HER2+/ER-disease, but none were associated with basal-like disease. We also observed subtype differences in the effects of SNPs in 2q35, 4p, TLR1, MAP3K1, ESR1, CDKN2A/B, ANKRD16, and ZM1Z1. Conclusion and Impact: We found evidence that genetic risk factors for breast cancer vary by subtype and further clarified the role of several key susceptibility genes. Cancer Epidemiol Biomarkers Prev; 23(1); 84-97. (C) 2013 AACR. C1 [O'Brien, Katie M.; Cole, Stephen R.; Engel, Lawrence S.; Bensen, Jeannette T.; Poole, Charles; Millikan, Robert C.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [O'Brien, Katie M.; Bensen, Jeannette T.; Millikan, Robert C.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Herring, Amy H.] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Herring, Amy H.] Univ N Carolina, Carolina Populat Ctr, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. RP O'Brien, KM (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. EM obrienkm2@niehs.nih.gov OI O'Brien, Katie/0000-0002-1931-1349; Engel, Lawrence/0000-0001-9268-4830 FU NCI NIH HHS [P50 CA058223, P30 CA016086, P30-CA16086, P50-CA58223, R25CA057726, R25 CA057726]; NIEHS NIH HHS [P30 ES010126] NR 90 TC 10 Z9 10 U1 3 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2014 VL 23 IS 1 BP 84 EP 97 DI 10.1158/1055-9965.EPI-13-0463 PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZB UT WOS:000335143400010 PM 24177593 ER PT J AU Lubin, JH De Stefani, E Abnet, CC Acosta, G Boffetta, P Victora, C Graubard, BI Munoz, N Deneo-Pellegrini, H Franceschi, S Castellsague, X Ronco, AL Dawsey, SM AF Lubin, Jay H. De Stefani, Eduardo Abnet, Christian C. Acosta, Gisele Boffetta, Paolo Victora, Cesar Graubard, Barry I. Munoz, Nubia Deneo-Pellegrini, Hugo Franceschi, Silvia Castellsague, Xavier Ronco, Alvaro L. Dawsey, Sanford M. TI Mate Drinking and Esophageal Squamous Cell Carcinoma in South America: Pooled Results from Two Large Multicenter Case-Control Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; ILEX-PARAGUARIENSIS; BLADDER-CANCER; HOT BEVERAGES; RISK; URUGUAY; TOBACCO; CONSUMPTION; ALCOHOL; DIET AB Background: Mate tea is a nonalcoholic infusion widely consumed in southern South America, and may increase risk of esophageal squamous cell carcinoma (ESCC) and other cancers due to polycyclic aromatic hydrocarbons (PAH) and/or thermal injury. Methods: We pooled two case-control studies: a 1988 to 2005 Uruguay study and a 1986 to 1992 multinational study in Argentina, Brazil, Paraguay, and Uruguay, including 1,400 cases and 3,229 controls. We computed ORs and fitted a linear excess OR (EOR) model for cumulative mate consumption in liters/day-year (LPDY). Results: The adjusted OR for ESCC with 95% confidence interval (CI) by ever compared with never use of mat e was 1.60 (1.2-2.2). ORs increased linearly with LPDY (test of nonlinearity; P -0.69). The estimate of slope (EOR/LPDY) was 0.009 (0.005-0.014) and did not vary with daily intake, indicating mate intensity did not influence the strength of association. EOR/LPDY estimates for consumption at warm, hot, and very hot beverage temperatures were 0.004 (-0.002-0.013), 0.007 (0.003-0.013), and 0.016 (0.009-0.027), respectively, and differed significantly (P < 0.01). EOR/LPDY estimates were increased in younger (< 65) individuals and never alcohol drinkers, but these evaluations were post hoc, and were homogeneous by sex. Conclusions: ORs for ESCC increased linearly with cumulative mate consumption and were unrelated to intensity, so greater daily consumption for shorter duration or lesser daily consumption for longer duration resulted in comparable ORs. The strength of association increased with higher mate temperatures. Impact: Increased understanding of cancer risks with mate consumption enhances the understanding of the public health consequences given its purported health benefits. C1 [Lubin, Jay H.; Graubard, Barry I.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Abnet, Christian C.; Dawsey, Sanford M.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [De Stefani, Eduardo] Univ Republica, Sch Med, Dept Pathol, Epidemiol Grp, Montevideo, Uruguay. [Acosta, Gisele] Univ Republica, Sch Med, Dept Pathol, Montevideo, Uruguay. [Deneo-Pellegrini, Hugo] Pereira Rossell Womens Hosp, Dept Pathol, Inst Canc, Montevideo, Uruguay. [Ronco, Alvaro L.] Pereira Rossell Womens Hosp, Unit Oncol & Radiotherapy, Montevideo, Uruguay. [Ronco, Alvaro L.] IUCLAEH Sch Med, Maldonado, Uruguay. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Victora, Cesar] Univ Fed Pelotas, Postgrad Program Epidemiol, Pelotas, RS, Brazil. [Munoz, Nubia] Canc Inst Colombia, Bogota, Colombia. [Franceschi, Silvia] Int Agcy Res Canc, Infect & Canc Epidemiol Grp, F-69372 Lyon, France. [Castellsague, Xavier] CIBERESP, Catalan Inst Oncol ICO, IDIBELL, Catalonia 08908, Spain. RP Lubin, JH (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM lubinj@exchange.nih.gov RI Abnet, Christian/C-4111-2015; Epidemiologicas, Centro de pesquisas /D-4561-2013; Castellsague Pique, Xavier/N-5795-2014; Victora, Cesar/D-4476-2013; OI Abnet, Christian/0000-0002-3008-7843; Castellsague Pique, Xavier/0000-0002-0802-3595; Victora, Cesar/0000-0002-2465-2180 FU IARC, Lyon, France [IARC/CRA ECE/98/17]; IARC [FIS 97/0662]; Fondo para la Investigacion Cientifica y Tecnologica (Argentina); Institut Municipal d'Investigacio Medica (Barcelona); Fundacao de Amparo a Pesquisa no Estado de Sao Paulo [01/01768-2]; European Commission [IC18-CT97-0222]; Comision Honoraria de Lucha contra el Cancer [5471-066]; International Union Against Cancer; National Cancer Institute; NIH [N01-CO-65341]; National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This work was supported by the IARC, Lyon, France [Uruguay study; to E. De Stefani, H. Deneo-Pellegrini, A. L. Ronco, and G. Acosta (IARC/CRA ECE/98/17)]. X. Castellsague, C. Victora, and E. De Stefani, the IARC study and its components were supported with grants from IARC to Fondo de Investigaciones Sanitarias (Spain; FIS 97/0662), Fondo para la Investigacion Cientifica y Tecnologica (Argentina), Institut Municipal d'Investigacio Medica (Barcelona), Fundacao de Amparo a Pesquisa no Estado de Sao Paulo (01/01768-2), and from the European Commission (IC18-CT97-0222), the Comision Honoraria de Lucha contra el Cancer (Montevideo, Uruguay; 5471-066), the International Union Against Cancer, the International Cancer Research Data Bank Program of the National Cancer Institute, and the NIH (Bethesda, MD; N01-CO-65341). J. H. Lubin, C. C. Abnet, B. I. Graubard, and S. M. Dawsey were supported by the Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 35 TC 9 Z9 9 U1 2 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2014 VL 23 IS 1 BP 107 EP 116 DI 10.1158/1055-9965.EPI-13-0796 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZB UT WOS:000335143400012 PM 24130226 ER PT J AU Marks, MA Chaturvedi, AK Kelsey, K Straif, K Berthiller, J Schwartz, SM Smith, E Wyss, A Brennan, P Olshan, AF Wei, QY Sturgis, EM Zhang, ZF Morgenstern, H Muscat, J Lazarus, P McClean, M Chen, C Vaughan, TL Wunsch, V Curado, MP Koifman, S Matos, E Menezes, A Daudt, AW Fernandez, L Posner, M Boffetta, P Lee, YCA Hashibe, M D'Souza, G AF Marks, Morgan A. Chaturvedi, Anil K. Kelsey, Karl Straif, Kurt Berthiller, Julien Schwartz, Stephen M. Smith, Elaine Wyss, Annah Brennan, Paul Olshan, Andrew F. Wei, Qingyi Sturgis, Erich M. Zhang, Zuo-Feng Morgenstern, Hal Muscat, Joshua Lazarus, Philip McClean, Michael Chen, Chu Vaughan, Thomas L. Wunsch-Filho, Victor Curado, Maria Paula Koifman, Sergio Matos, Elena Menezes, Ana Daudt, Alexander W. Fernandez, Leticia Posner, Marshall Boffetta, Paolo Lee, Yuan-Chin Amy Hashibe, Mia D'Souza, Gypsyamber TI Association of Marijuana Smoking with Oropharyngeal and Oral Tongue Cancers: Pooled Analysis from the INHANCE Consortium SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SQUAMOUS-CELL CARCINOMA; AGED 45 YEARS; HUMAN-PAPILLOMAVIRUS; UNITED-STATES; RISK-FACTORS; NECK-CANCER; ENDOCANNABINOID SYSTEM; SENSITIVITY-ANALYSIS; INCIDENCE TRENDS; CANNABIS USE AB Background: The incidence of oropharyngeal and oral tongue cancers has increased over the last 20 years which parallels increased use of marijuana among individuals born after 1950. Methods: A pooled analysis was conducted comprising individual-level data from nine case-control studies from the United States and Latin America in the INHANCE consortium. Self-reported information on marijuana smoking, demographic, and behavioral factors was obtained from 1,921 oropharyngeal cases, 356 oral tongue cases, and 7,639 controls. Results: Compared with never marijuana smokers, ever marijuana smokers had an elevated risk of oropharyngeal [adjusted OR (aOR), 1.24; 95% confidence interval (CI): 1.06-1.47] and a reduced risk of oral tongue cancer (aOR, 0.47; 95% CI, 0.29, 0.75). The risk of oropharyngeal cancer remained elevated among never tobacco and alcohol users. The risk of oral tongue cancer was reduced among never users of tobacco and alcohol. Sensitivity analysis adjusting for potential confounding by HPV exposure attenuated the association of marijuana use with oropharyngeal cancer (aOR, 0.99; 95% CI, 0.71-1.25), but had no effect on the oral tongue cancer association. Conclusions: These results suggest that the association of marijuana use with head and neck carcinoma may differ by tumor site. Impact: The associations of marijuana use with oropharyngeal and oral tongue cancer are consistent with both possible pro-and anticarcinogenic effects of cannabinoids. Additional work is needed to rule out various sources of bias, including residual confounding by HPV infection and misclassification of marijuana exposure. (C) 2013 AACR. C1 [Marks, Morgan A.; Chaturvedi, Anil K.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Posner, Marshall] Johns Hopkins Sch Med, Baltimore, MD USA. [D'Souza, Gypsyamber] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Kelsey, Karl] Brown Univ, Sch Med, Dept Community Hlth, Providence, RI 02912 USA. [Straif, Kurt; Berthiller, Julien; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Berthiller, Julien] Hosp Civils Lyon, Lyon, France. [Berthiller, Julien] Univ Lyon 1, Equipe Accueil 4129, F-69365 Lyon, France. [Curado, Maria Paula; Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. [Schwartz, Stephen M.; Chen, Chu; Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Smith, Elaine] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. [Wyss, Annah; Olshan, Andrew F.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Wei, Qingyi; Sturgis, Erich M.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg & Epidemiol, Houston, TX 77030 USA. [Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Muscat, Joshua; Lazarus, Philip] Penn State Coll Med, Hershey, PA USA. [McClean, Michael] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Wunsch-Filho, Victor] Univ Sao Paulo, Fac Saude Publ, Sao Paulo, Brazil. [Koifman, Sergio] Fundacao Oswaldo Cruz, Escola Nacl Saude Publ, Rio De Janeiro, Brazil. [Menezes, Ana] Univ Fed Pelotas, Pelotas, Brazil. [Daudt, Alexander W.] Hosp Clin Porto Alegre, Port Alegre, Brazil. [Matos, Elena] Univ Buenos Aires, Inst Oncol Angel H Roffo, Buenos Aires, DF, Argentina. [Fernandez, Leticia] Inst Oncol & Radiobiol, Havana, Cuba. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Lee, Yuan-Chin Amy; Hashibe, Mia] Univ Utah, Sch Med, Salt Lake City, UT USA. RP D'Souza, G (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, 615 N Wolfe St,Rm E6132B, Baltimore, MD 21205 USA. EM gdsouza@jhsph.edu RI McClean, Michael/J-2934-2015; Chaturvedi, Anil/J-2024-2015; Menezes, Ana/G-7266-2012; Curado, Maria Paula/M-6200-2013; OI Chaturvedi, Anil/0000-0003-2696-8899; Curado, Maria Paula/0000-0001-8172-2483; Schwartz, Stephen/0000-0001-7499-8502 FU INHANCE Pooled data project [R03CA113157 (NCI), R03DE016611(NIDCR)]; Intramural Research Program of the National Cancer Institute; NIH [R01DE021395 (NIDCR)]; Study specific funding: Seattle (Schwartz) study: NIH [R01CA048996, R01DE012609]; Tampa study: NIH [P01CA068384, K07CA104231, R01DE013158]; Los Angeles study: NIH [P50CA090388, R01DA011386, R03CA077954, T32CA009142, U01CA096134, R21ES011667]; Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center; Houston study: NIH [R01ES011740, R01CA100264]; Latin America Study: Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina, IMIM (Barcelona); Fundacao de Amparo a Pesquisa no Estado de Sao Paulo (FAPESP) [01/01768-2]; European Commission [IC18-CT97-0222]; Boston study: NIH [R01CA078609, R01CA100679]; Seattle: NIH [R01CA030022]; Baltimore (HOTSPOT; Johns Hopkins Richard Gelb Cancer Prevention Award); North Carolina study: National Cancer Institute [R01-CA90731] FX This project has been funded in part with funds from the INHANCE Pooled data project [R03CA113157 (NCI), R03DE016611(NIDCR)] and the Intramural Research Program of the National Cancer Institute, NIH, and by support from R01DE021395 (NIDCR). Study specific funding: Seattle (Schwartz) study: NIH grants (R01CA048996, R01DE012609); Tampa study: NIH grants (P01CA068384, K07CA104231, R01DE013158); Los Angeles study: NIH grants (P50CA090388, R01DA011386, R03CA077954, T32CA009142, U01CA096134, R21ES011667), and grants from the Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center; Houston study: NIH grants (R01ES011740, R01CA100264); Latin America Study: Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina, IMIM (Barcelona), Fundacao de Amparo a Pesquisa no Estado de Sao Paulo (FAPESP; No 01/01768-2), and European Commission (IC18-CT97-0222); Boston study: NIH grants (R01CA078609, R01CA100679); Seattle (Vaughan): NIH grant (R01CA030022); Baltimore (HOTSPOT; Johns Hopkins Richard Gelb Cancer Prevention Award); North Carolina study: National Cancer Institute (R01-CA90731). NR 47 TC 7 Z9 8 U1 3 U2 22 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2014 VL 23 IS 1 BP 160 EP 171 DI 10.1158/1055-9965.EPI-13-0181 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZB UT WOS:000335143400018 PM 24351902 ER PT J AU Purdue, MP Ye, YQ Wang, ZM Colt, JS Schwartz, KL Davis, FG Rothman, N Chow, WH Wu, XF Chanock, SJ AF Purdue, Mark P. Ye, Yuanqing Wang, Zhaoming Colt, Joanne S. Schwartz, Kendra L. Davis, Faith G. Rothman, Nathaniel Chow, Wong-Ho Wu, Xifeng Chanock, Stephen J. TI A Genome-Wide Association Study of Renal Cell Carcinoma among African Americans SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CYCLIN D1; SUSCEPTIBILITY LOCUS; GENETIC-BASIS; CANCER; EXPRESSION; RISK; METAANALYSIS; GENOTYPE; 11Q13.3; DISEASE AB Genomewide association studies (GWAS) of renal cell carcinoma (RCC) in populations of European ancestry have identified four susceptibility loci. No GWAS has been conducted among African Americans (AA), who experience a higher incidence of RCC. We conducted a GWAS in which we analyzed 1,136,723 common singlenucleotide polymorphisms (SNP) among 255 cases and 375 controls of African ancestry, and further investigated 16 SNPs in a replication set (140 cases and 543 controls). The 12p11.23 variant rs10771279, located 77 kb from the Europeanancestry RCC marker rs718314, was associated with RCC risk in the GWAS (P = 1.2 Chi 10(-7)) but did not replicate (P = 0.99). Consistent with Europeanancestry findings, the A allele of rs7105934 on 11q13.3 was associated with decreased risk [ OR, 0.76, 95% confidence interval (CI), 0.640.91; P = 0.0022]. The frequency of this allele was higher than that observed in the Europeanancestry GWAS (0.56 and 0.07, respectively, among controls). The rs7105934 association was stronger for clear cellRCC (ccRCC: OR, 0.56; P = 7.4 Chi 10(-7)) and absent for cases of other or unknown histology (OR, 1.02; P = 0.86). Analyses of rs7105934 by subtype among Europeanancestry participants from these studies yielded similar findings (ORs 0.69 and 0.92, respectively). This study provides, to our knowledge, the first evidence that rs7105934 is an RCC susceptibility locus among AAs. Our finding that the association with this SNP may be specific to clearcell RCC is novel and requires additional investigation. Additional investigation of rs10771279 and other suggestiveGWASfindings is also needed. C1 [Purdue, Mark P.; Wang, Zhaoming; Colt, Joanne S.; Rothman, Nathaniel; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. [Ye, Yuanqing; Chow, Wong-Ho; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA. [Schwartz, Kendra L.] Wayne State Univ, Sch Med, Dept Family Med & Publ Hlth Sci, Detroit, MI USA. [Schwartz, Kendra L.] Wayne State Univ, Sch Med, Barbara Ann Karmanos Inst, Detroit, MI USA. [Davis, Faith G.] Univ Alberta, Dept Publ Hlth Sci, Edmonton, AB, Canada. RP Purdue, MP (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E604, Rockville, MD 20850 USA. EM purduem@mail.nih.gov RI Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 FU Intramural Research Program of the NCI [CA098897]; MD Anderson Research Trust FX This research was supported by the Intramural Research Program of the NCI (NCI study) and NCI grant CA098897 and MD Anderson Research Trust (X. Wu; MDACC study).; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C.Section 1734 solely to indicate this fact. NR 19 TC 5 Z9 8 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2014 VL 23 IS 1 BP 209 EP 214 DI 10.1158/1055-9965.EPI-13-0818 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZB UT WOS:000335143400023 PM 24220910 ER PT J AU Gronowski, AM Manson, JE Mardis, ER Mora, S Spong, CY AF Gronowski, Ann M. Manson, JoAnn E. Mardis, Elaine R. Mora, Samia Spong, Catherine Y. TI What's Different about Women's Health? SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Gronowski, Ann M.] Washington Univ, Sch Med, Div Lab & Genom Med, St Louis, MO 63110 USA. [Manson, JoAnn E.; Mora, Samia] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. [Mardis, Elaine R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Mora, Samia] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Spong, Catherine Y.] Eunnice Kennedy Shriver Natl Inst Child Hlth & Hu, Div Extramural Res, NIH, Bethesda, MD USA. RP Gronowski, AM (reprint author), Washington Univ, Sch Med, Div Lab & Genom Med, Box 8118,660 S Euclid, St Louis, MO 63110 USA. EM gronowski@wustl.edu NR 25 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2014 VL 60 IS 1 BP 1 EP 3 DI 10.1373/clinchem.2013.216598 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AG0ZZ UT WOS:000335145900001 PM 24379307 ER PT J AU Nelson, LM AF Nelson, Lawrence M. TI Untitled commentary SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 Eunnice Kennedy Shriver Natl Inst Child Hlth & Hu, Intramural Res Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. RP Nelson, LM (reprint author), Eunnice Kennedy Shriver Natl Inst Child Hlth & Hu, Intramural Res Program Reprod & Adult Endocrinol, NIH, 10 Ctr Dr,Bldg 10,Rm 1-3140, Bethesda, MD 20892 USA. EM lawrence.nelson@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2014 VL 60 IS 1 BP 33 EP 33 DI 10.1373/clinchem.2013.217257 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AG0ZZ UT WOS:000335145900009 ER PT J AU Le Gallo, M Bell, DW AF Le Gallo, Matthieu Bell, Daphne W. TI The Emerging Genomic Landscape of Endometrial Cancer SO CLINICAL CHEMISTRY LA English DT Review ID UTERINE SEROUS CARCINOMA; DNA MISMATCH REPAIR; MICROSATELLITE INSTABILITY; GERMLINE MUTATIONS; HIGH-FREQUENCY; BETA-CATENIN; GRADE; EXPRESSION; GENES; PTEN AB BACKGROUND: Endometrial cancer is responsible for approximately 74 000 deaths annually among women worldwide. It is a heterogeneous disease comprising multiple histologic subtypes. In the US, the majority of deaths from endometrial carcinoma are attributed to the serous and endometrioid subtypes. An understanding of the fundamental genomic alterations that drive serous and endometrioid endometrial carcinomas lays the foundation for the identification of molecular markers that could improve the clinical management of patients presenting with these tumors. CONTENT: We review the current state of knowledge regarding somatic genomic alterations that occur in serous and endometrioid endometrial tumors. We present this knowledge in a historical context by reviewing the genomic alterations that studies of individual genes and proteins have identified over the past 2 decades or so. We then review very recent comprehensive and systematic surveys of genomic, exomic, transcriptomic, epigenomic, and proteomic alterations in serous and endometrioid endometrial carcinomas. SUMMARY: The recent mapping of the genomic landscape of serous and endometrioid endometrial carcinomas has produced the first comprehensive molecular classification of these tumors, which has distinguished 4 molecular subgroups: a POLE [polymerase (DNA directed), epsilon, catalytic subunit] ultramutated subgroup, a hypermutated/microsatellite-unstable subgroup, a copy number-low/microsatellite-stable subgroup, and a copy number-high subgroup. This molecular classification may ultimately serve to refine the diagnosis and treatment of women with endometrioid and serous endometrial tumors. (C) 2013 American Association for Clinical Chemistry C1 [Le Gallo, Matthieu; Bell, Daphne W.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Bell, DW (reprint author), NHGRI, Canc Genet Branch, 50 South Dr,MSC 8000, Bethesda, MD 20892 USA. EM belldaph@mail.nih.gov FU Intramural Program of the National Institutes of Health FX D.W. Bell, Intramural Program of the National Institutes of Health NR 75 TC 16 Z9 17 U1 0 U2 8 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2014 VL 60 IS 1 BP 98 EP 110 DI 10.1373/clinchem.2013.205740 PG 13 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AG0ZZ UT WOS:000335145900018 PM 24170611 ER PT J AU Sacks, DB AF Sacks, David B. TI Diagnosis of Gestational Diabetes Mellitus: It Is Time for International Consensus SO CLINICAL CHEMISTRY LA English DT Article ID PREGNANCY OUTCOMES; SCREENING-TESTS; CLASSIFICATION; CRITERIA; RECOMMENDATIONS; HYPERGLYCEMIA; GUIDELINES C1 [Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Sacks, DB (reprint author), Dept Lab Med, Bldg 10,Rm 2C306,10 Ctr Dr, Bethesda, MD 20892 USA. EM sacksdb@mail.nih.gov OI Sacks, David/0000-0003-3100-0735 FU Intramural Research Program of the NIH FX D.B. Sacks, Intramural Research Program of the NIH. NR 14 TC 12 Z9 12 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2014 VL 60 IS 1 BP 141 EP 143 DI 10.1373/clinchem.2013.206920 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AG0ZZ UT WOS:000335145900023 PM 24061614 ER PT J AU Goto, A Chen, BH Song, YQ Cauley, J Cummings, SR Farhat, GN Gunter, M Van Horn, L Howard, BV Jackson, R Lee, J Rexrode, KM Liu, SM AF Goto, Atsushi Chen, Brian H. Song, Yiqing Cauley, Jane Cummings, Steven R. Farhat, Ghada N. Gunter, Marc Van Horn, Linda Howard, Barbara V. Jackson, Rebecca Lee, Jennifer Rexrode, Kathryn M. Liu, Simin TI Age, Body Mass, Usage of Exogenous Estrogen, and Lifestyle Factors in Relation to Circulating Sex Hormone-Binding Globulin Concentrations in Postmenopausal Women SO CLINICAL CHEMISTRY LA English DT Article ID PHYSICAL-ACTIVITY; CLINICAL-TRIAL; MIDLIFE WOMEN; HEALTH; RISK; METAANALYSIS; INSULIN; TESTOSTERONE; CAFFEINE; CANCER AB BACKGROUND: Circulating concentrations of sex hormone-binding globulin (SHBG) have been associated with cardiovascular diseases, type 2 diabetes, metabolic syndrome, and hormone-dependent cancers; however, correlates of SHBG concentrations are not well understood. METHODS: We comprehensively investigated correlates of SHBG concentrations among 13 547 women who participated in the Women's Health Initiative and who had SHBG measurements. We estimated study-and ethnicity-specific associations of age, reproductive history, usage of exogenous estrogen, body mass index (BMI), and lifestyle factors such as physical activity, smoking, alcohol consumption, coffee intake, and dietary factors with SHBG concentrations. These estimates were pooled using random-effects models. We also examined potential nonlinear associations using spline analyses. RESULTS: There was no significant ethnic difference in the age-adjusted mean concentrations of SHBG. Age, exogenous estrogen use, physical activity, and regular coffee intake were positively associated with SHBG concentrations, whereas BMI was inversely associated with SHBG concentrations after adjustment for potential confounding factors. Similar patterns were observed among both ever users and never users of exogenous estrogen. The spline analysis indicated nonlinear relations of regular intake of coffee, age, and BMI with SHBG concentrations. Two or more cups/day of regular coffee consumption and age of 60 years or older were associated with higher SHBG concentrations; the inverse BMI-SHBG relation was especially strong among women whose BMI was below 30. CONCLUSIONS: In this large sample of postmenopausal women, age, exogenous estrogen use, physical activity, regular coffee intake, and BMI were significant correlates of SHBG concentrations, presenting potential targets for interventions. (C) 2013 American Association for Clinical Chemistry C1 [Goto, Atsushi] Natl Ctr Global Hlth & Med, Diabet Res Ctr, Dept Diabet Res, Tokyo, Japan. [Chen, Brian H.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Song, Yiqing; Rexrode, Kathryn M.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Song, Yiqing; Rexrode, Kathryn M.] Harvard Univ, Sch Med, Boston, MA USA. [Cauley, Jane] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, San Francisco, CA USA. [Farhat, Ghada N.] Univ Balamand, Beirut, Lebanon. [Gunter, Marc] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Van Horn, Linda] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Howard, Barbara V.] Medstar Res Inst, Washington, DC USA. [Jackson, Rebecca] Ohio State Univ, Dept Internal Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Lee, Jennifer] Univ Calif Davis, Dept Internal Med, Sacramento, CA 95817 USA. [Liu, Simin] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Liu, Simin] Brown Univ, Dept Med, Providence, RI 02912 USA. [Liu, Simin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. RP Liu, SM (reprint author), Brown Univ, Dept Epidemiol, Box G-S121-2,121 South Main St, Providence, RI 02912 USA. EM simin_liu@brown.edu RI Liu, Simin/I-3689-2014; Cauley, Jane/N-4836-2015; OI Liu, Simin/0000-0003-2098-3844; Cauley, Jane/0000-0003-0752-4408; Rexrode, Kathryn/0000-0003-3387-8429; Goto, Atsushi/0000-0003-0669-654X FU National Heart, Lung, and Blood Institute (NHLBI); NIH [R01 DK066401]; US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; Burroughs Wellcome Fund Interschool Training Program in Metabolic Diseases FX The WHI is funded by the National Heart, Lung, and Blood Institute (NHLBI), NIH, R01 DK066401, and US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. B. H. Chen, the Burroughs Wellcome Fund Interschool Training Program in Metabolic Diseases; R. D. Jackson, NIH; S. Liu, the Burroughs Wellcome Fund Interschool Training Program in Metabolic Diseases. NR 38 TC 6 Z9 6 U1 1 U2 7 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2014 VL 60 IS 1 BP 174 EP 185 DI 10.1373/clinchem.2013.207217 PG 12 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AG0ZZ UT WOS:000335145900030 PM 24048437 ER PT J AU Daniels, SI Soule, EE Davidoff, KS Bernbaum, JG Hu, DS Maeda, K Stahl, SJ Naiman, NE Waheed, AA Freed, EO Wingfield, P Yarchoan, R Davis, DA AF Daniels, Sarah I. Soule, Erin E. Davidoff, Katharine S. Bernbaum, John G. Hu, Duosha Maeda, Kenji Stahl, Stephen J. Naiman, Nicole E. Waheed, Abdul A. Freed, Eric O. Wingfield, Paul Yarchoan, Robert Davis, David A. TI Activation of virus uptake through induction of macropinocytosis with a novel polymerizing peptide SO FASEB JOURNAL LA English DT Article DE retrovirus; cytochalasin D; cellular uptake; endocytosis ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL VECTORS; TRANSDUCTION DOMAIN; THERAPEUTIC AGENTS; HIV-1 REPLICATION; MAMMALIAN-CELLS; TYPE-1 PROTEASE; AMYLOID FIBRILS; ENTERS CELLS; PROTEINS AB A 27-aa peptide (P27) was previously shown to decrease the accumulation of human immunodeficiency virus type 1 (HIV-1) in the supernatant of chronically infected cells; however, the mechanism was not understood. Here, we show that P27 prevents virus accumulation by inducing macropinocytosis (MPC). Treatment of HIV-1- and human T-cell lymphotropic virus type 1 (HTLV-1)-infected cells with 2-10 M P27 caused cell membrane ruffling and uptake of virus and polymerized forms of the peptide into large vacuoles. As demonstrated by electron microscopy, activation of MPC did not require virus or cells infected with virus, as P27 initiated its own uptake in the absence of virus. Inhibitors of MPC, Cytochalasin D and amiloride, decreased P27-mediated uptake of soluble dextran and inhibited P27-induced virus uptake by >60%, which provides further evidence that P27 induces MPC. In CD4(+) HeLa cells, HIV-1 infection was enhanced by P27 up to 4-fold, and P27 increased infection at concentrations as low as 20 nM. The 5-aa C-terminal domain of P27 was necessary for virus uptake and may be responsible for the polymerization of P27 into fibrils. These forms of P27 may play a key role in triggering MPC, making this peptide a useful tool for studying virus uptake and infection, as well as MPC of other macromolecules.Daniels, S.I., Soule, E.E., Davidoff, K.S., Bernbaum, J.G., Hu, D., Maeda, K., Stahl, S.J., Naiman, N.E., Waheed, A.E., Freed, E.O., Wingfield, P., Yarchoan, R., Davis. D.A. Activation of virus uptake through induction of macropinocytosis with a novel polymerizing peptide. C1 [Daniels, Sarah I.; Soule, Erin E.; Davidoff, Katharine S.; Hu, Duosha; Maeda, Kenji; Naiman, Nicole E.; Yarchoan, Robert; Davis, David A.] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Frederick, MD 21701 USA. [Waheed, Abdul A.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Stahl, Stephen J.; Wingfield, Paul] NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. [Bernbaum, John G.] NIAID, Supporting Integrated Res Facil, Div Clin Res, NIH, Bethesda, MD 20892 USA. RP Davis, DA (reprint author), NIH, 10 Ctr Dr,Bldg 10,Rm 6N106,MSC 1868, Bethesda, MD 20892 USA. EM dadavis@helix.nih.gov FU Intramural Research Program of the Center for Cancer Research; National Cancer Institute; U.S. National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the Center for Cancer Research, the National Cancer Institute, the U.S. National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and National Institute of Allergy and Infectious Diseases. The authors thank Yuki Takamatsu and Philippe Kieffer for technical help with flow cytometry and flow cytometry analysis. NR 48 TC 1 Z9 1 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JAN PY 2014 VL 28 IS 1 BP 106 EP 116 DI 10.1096/fj.13-238113 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AD8OS UT WOS:000333526100013 PM 24097312 ER PT J AU Cheung, GYC Kretschmer, D Queck, SY Joo, HS Wang, R Duong, AC Nguyen, TH Bach, THL Porter, AR DeLeo, FR Peschel, A Otto, M AF Cheung, Gordon Y. C. Kretschmer, Dorothee Queck, Shu Y. Joo, Hwang-Soo Wang, Rong Duong, Anthony C. Nguyen, Thuan H. Bach, Thanh-Huy L. Porter, Adeline R. DeLeo, Frank R. Peschel, Andreas Otto, Michael TI Insight into structure-function relationship in phenol-soluble modulins using an alanine screen of the phenol-soluble modulin ( PSM) alpha 3 peptide SO FASEB JOURNAL LA English DT Article DE Staphylococcus aureus; toxins; neutrophils; hemolysis; inflammation; biofilm ID RESISTANT STAPHYLOCOCCUS-AUREUS; VIRULENCE DETERMINANTS; ACTIVATES NEUTROPHILS; BIOFILM MATURATION; RECEPTOR; INFECTIONS; MODEL; EPIDERMIDIS; MECHANISMS; SKIN AB Phenol-soluble modulins (PSMs) are a family of peptides with multiple functions in staphylococcal pathogenesis. To gain insight into the structural features affecting PSM functions, we analyzed an alanine substitution library of PSM3, a strongly cytolytic and proinflammatory PSM of Staphylococcus aureus with a significant contribution to S. aureus virulence. Lysine residues were essential for both receptor-dependent proinflammatory and receptor-independent cytolytic activities. Both phenotypes also required additional structural features, with the C terminus being crucial for receptor activation. Biofilm formation was affected mostly by hydrophobic amino acid positions, suggesting that the capacity to disrupt hydrophobic interactions is responsible for the effect of PSMs on biofilm structure. Antimicrobial activity, absent from natural PSM3, could be created by the exchange of large hydrophobic side chains, indicating that PSM3 has evolved to exhibit cytolytic rather than antimicrobial activity. In addition to gaining insight into the structure-function relationship in PSMs, our study identifies nontoxic PSM3 derivatives for active vaccination strategies and lays the foundation for future efforts aimed to understand the biological role of PSM recognition by innate host defense.Cheung, G. Y., Kretschmer, D., Queck, S. Y., Joo, H.-S., Wang, R., Duong, A. C., Nguyen, T. H., Bach, T.-H., Porter, A. R., DeLeo, F. R., Peschel, A., Otto, M. Insight into structure-function relationship in phenol-soluble modulins using an alanine screen of the phenol-soluble modulin (PSM) 3 peptide. C1 [Cheung, Gordon Y. C.; Queck, Shu Y.; Joo, Hwang-Soo; Wang, Rong; Duong, Anthony C.; Nguyen, Thuan H.; Bach, Thanh-Huy L.; Otto, Michael] NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. [Kretschmer, Dorothee; Peschel, Andreas] Univ Tubingen, Interfac Inst Microbiol & Infect Med, Cellular & Mol Microbiol Div, Tubingen, Germany. [Porter, Adeline R.; DeLeo, Frank R.] NIAID, Pathogen Host Cell Biol Sect, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT USA. RP Otto, M (reprint author), NIAID, 9000 Rockville Pike,Bldg 33 1W10, Bethesda, MD 20892 USA. EM motto@niaid.nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), U.S. National Institutes of Health (NIH); German Research Foundation [SFB685, TRR34]; German Ministry of Education and Research; Interdisziplin res Zentrum fur Klinische Forschung (IZKF) Program of the Medical Faculty, University of Tubingen FX The authors thank Nele Nikola, Kevin Holmes, and David Stephany for technical help; Michael Dolan for PSM alpha 3 modeling; Francois Boulay (Commissariat a l'Energie Atomique, Grenoble, France) for FPR1 and FPR2-transfected cell lines; and Bas Surewaard for advice on the in vivo studies. This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), U.S. National Institutes of Health (NIH) (to M.O. and F. D.), and grants from the German Research Foundation (SFB685, TRR34), the German Ministry of Education and Research (SkinStaph, Menage), and the Interdisziplin res Zentrum fur Klinische Forschung (IZKF) Program of the Medical Faculty, University of Tubingen (to A.P.). NR 39 TC 16 Z9 16 U1 2 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JAN PY 2014 VL 28 IS 1 BP 153 EP 161 DI 10.1096/fj.13-232041 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AD8OS UT WOS:000333526100017 PM 24008753 ER PT J AU Shi, J Birnbaumer, L Large, WA Albert, AP AF Shi, Jian Birnbaumer, Lutz Large, William A. Albert, Anthony P. TI Myristoylated alanine-rich C kinase substrate coordinates native TRPC1 channel activation by phosphatidylinositol 4,5-bisphosphate and protein kinase C in vascular smooth muscle SO FASEB JOURNAL LA English DT Article DE Ca2+ signaling; calmodulin; transgenic ID CORONARY-ARTERY MYOCYTES; MARCKS PROTEIN; CATION CHANNEL; ANGIOTENSIN-II; CALMODULIN; PIP2; INHIBITION; CELLS; PKC; DIACYLGLYCEROL AB Canonical transient receptor potential 1 (TRPC1) Ca2+-permeable cation channels contribute to vascular tone and blood vessel remodeling and represent potential therapeutic targets for cardiovascular disease. Protein kinase C (PKC) and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P-2] are obligatory for native TRPC1 channel activation in vascular smooth muscle cells (VSMCs) but how PKC and PI(4,5)P-2 act together to induce channel gating remains unresolved. The present study reveals that myristoylated alanine-rich C kinase substrate (MARCKS) protein coordinates activation of TRPC1 channels by PKC and PI(4,5)P-2. TRPC1 channels and MARCKS form signaling complexes with PI(4,5)P-2 bound to MARCKS; in this configuration TRPC1 channels are closed. Activators of TRPC1 channels induce PKC phosphorylation of TRPC1 proteins, which causes dissociation of TRPC1 subunits from MARCKS and release of PI(4,5)P-2 from MARCKS; PI(4,5)P-2 subsequently binds to TRPC1 subunits to induce channel opening. Calmodulin acting at, or upstream of, MARCKS is also required for TRPC1 channel opening through a similar gating mechanism involving PKC and PI(4,5)P-2. These novel findings show that MARCKS coordinates native TRPC1 channel activation in VSMCs by acting as a reversible PI(4,5)P-2 buffer, which is regulated by PKC-mediated TRPC1 phosphorylation. Moreover, our data provide evidence that PI(4,5)P-2 is a gating ligand of TRPC1 channels.Shi, J., Birnbaumer, L., Large, W. A., and Albert, A. P. Myristoylated alanine-rich C kinase substrate coordinates native TRPC1 channel activation by phosphatidylinositol 4,5-bisphosphate and protein kinase C in vascular smooth muscle. C1 [Shi, Jian; Large, William A.; Albert, Anthony P.] Univ London, Dept Pharmacol & Cell Physiol, Div Biomed Sci, London SW17 0RE, England. [Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. RP Albert, AP (reprint author), Univ London, Div Biomed Sci, Cranmer Terrace, London SW17 0RE, England. EM aalbert@sgul.ac.uk FU UK Biotechnology and Biological Sciences Research Council [BB/J007226/1]; Intramural Research Program of the U.S. National Institutes of Health [z01-ES-101684] FX This work was supported by the UK Biotechnology and Biological Sciences Research Council (BB/J007226/1 to A. P. A.) and by the Intramural Research Program of the U.S. National Institutes of Health (project z01-ES-101684 to L.B.). NR 36 TC 11 Z9 12 U1 1 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JAN PY 2014 VL 28 IS 1 BP 244 EP 255 DI 10.1096/fj.13-238022 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AD8OS UT WOS:000333526100024 PM 24022404 ER PT J AU Chen, KH Dasgupta, A Ding, JH Indig, FE Ghosh, P Longo, DL AF Chen, Kuang-Hueih Dasgupta, Asish Ding, Jinhui Indig, Fred E. Ghosh, Paritosh Longo, Dan L. TI Role of mitofusin 2 ( Mfn2) in controlling cellular proliferation SO FASEB JOURNAL LA English DT Article DE HSG; Ras; Raf; ERK ID TUMOR-SUPPRESSOR; RASSF FAMILY; APOPTOSIS; DOMAIN; EXPRESSION; MUTATIONS; PATHWAY AB It has been reported that Mitofusin2 (Mfn2) inhibits cell proliferation when overexpressed. We wanted to study the role of endogenous Mfn2 in cell proliferation, along with the structural features of Mfn2 that influence its mitochondrial localization and control of cell proliferation. Mfn2-knockdown clones of a B-cell lymphoma cell line BJAB exhibited an increased rate of cell proliferation. A 2-fold increase in cell proliferation was also observed in Mfn2-knockout mouse embryonic fibroblast (MEF) cells as compared with the control wild-type cells, and the proliferative advantage of the knockout MEF cells was blocked on reintroduction of the Mfn2 gene. Mfn2 exerts its antiproliferative effect by acting as an effector molecule of Ras, resulting in the inhibition of the Ras-Raf-ERK signaling pathway. Furthermore, both the N-terminal (aa 1-264) and the C-terminal (aa 265-757) fragments of Mfn2 blocked cell proliferation through distinct mechanisms: the N-terminal-mediated inhibition was due to its interaction with Raf-1, whereas the C-terminal fragment of Mfn2 inhibited cell proliferation by interacting with Ras. The inhibition of proliferation by the N-terminal fragment was independent of its mitochondrial localization. Collectively, our data provide new insights regarding the role of Mfn2 in controlling cellular proliferation.Chen, K.-H., Dasgupta, A., Ding, J., Indig, F. E., Ghosh, P., Longo, D. L. Role of Mitofusin 2 (Mfn2) in controlling cellular proliferation. C1 [Chen, Kuang-Hueih; Dasgupta, Asish; Ghosh, Paritosh; Longo, Dan L.] NIA, Lymphocyte Cell Biol Unit, Genet Lab, Biomed Res Ctr,NIH, Baltimore, MD 21224 USA. [Ding, Jinhui] NIA, Bioinformat Facil, Neurogenet Lab, NIH, Baltimore, MD 21224 USA. [Indig, Fred E.] NIA, Confocal Imaging Facil, NIH, Baltimore, MD 21224 USA. [Chen, Kuang-Hueih] MedStar Res Inst, Baltimore, MD USA. RP Ghosh, P (reprint author), NIA, Lymphocyte Cell Biol Unit, Genet Lab, NIH,Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM kuanghueihchen@yahoo.com; ghoshp@grc.nia.nih.gov FU National Institutes of Health, National Institute on Aging FX The authors are grateful to Dr. David C. Chan (Division of Biology, California Institute of Technology, Pasadena, CA, USA) for WT and Mfn2-knockout MEFs. The authors thank Drs. Carl Sasaki and Jessica Curtis for technical assistance and Rachel Munk for help in editing the paper. The authors also thank the Flow Cytometry facility at the National Institute on Aging for help in cell cycle analysis. This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 26 TC 29 Z9 36 U1 0 U2 15 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JAN PY 2014 VL 28 IS 1 BP 382 EP 394 DI 10.1096/fj.13-230037 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AD8OS UT WOS:000333526100036 PM 24081906 ER PT J AU Jin, H Zhang, K Qiao, CY Yuan, AL Li, DW Zhao, L Shi, C Xu, XW Ni, SL Zheng, CY Liu, XH Yang, B Sun, HC AF Jin, Han Zhang, Kai Qiao, Chunyan Yuan, Anliang Li, Daowei Zhao, Liang Shi, Ce Xu, Xiaowei Ni, Shilei Zheng, Changyu Liu, Xiaohua Yang, Bai Sun, Hongchen TI Efficiently engineered cell sheet using a complex of polyethylenimine-alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE bone regeneration; bone tissue engineering; nanocomposites; cell sheet; bone morphogenetic protein 2 ID MARROW STROMAL CELLS; IN-VITRO; OSTEOGENIC DIFFERENTIATION; MESENCHYMAL CELLS; REGENERATING BONE; 3D SCAFFOLD; BMP-2 GENE; DEFECTS; DELIVERY; MICROSPHERES AB Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2) gene-engineered cell sheet using a complex of polyethylenimine-alginate (PEI-al) nanocomposites plus human BMP-2 complementary(c) DNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI-al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI-al nanocomposites efficiently deliver the BMP-2 gene to bone marrow mesenchymal stem cells and that BMP-2 gene-engineered cell sheet is an effective way for promoting bone regeneration. C1 [Jin, Han; Qiao, Chunyan; Yuan, Anliang; Li, Daowei; Zhao, Liang; Shi, Ce; Xu, Xiaowei; Ni, Shilei; Sun, Hongchen] Jilin Univ, Sch Stomatol, Dept Pathol, Changchun 130021, Peoples R China. [Zhang, Kai; Yang, Bai] Jilin Univ, Coll Chem, State Key Lab Supramol Struct & Mat, Changchun 130021, Peoples R China. [Zheng, Changyu] NIDCD, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. [Liu, Xiaohua] Texas A&M Univ, Baylor Coll Dent, Dept Biomed Sci, Dallas, TX USA. RP Sun, HC (reprint author), Jilin Univ, Sch Stomatol, Dept Pathol, 1500 Qinghua Rd, Changchun 130021, Peoples R China. EM hcsun@jlu.edu.cn RI Liu, Xiaohua/L-7766-2014 OI Liu, Xiaohua/0000-0003-0177-0886 FU National Natural Science Foundation of China [81320108011, 81271111, 30830108]; Research Fund for the Doctoral Program of Higher Education of China [233200801830063, 20120061130010]; Science Technology Development Program of Jilin Province [2011 I 051] FX This work was supported by the National Natural Science Foundation of China (81320108011, 81271111, 30830108), the Research Fund for the Doctoral Program of Higher Education of China (233200801830063, 20120061130010), and the Science Technology Development Program of Jilin Province (2011 I 051). NR 38 TC 6 Z9 7 U1 2 U2 23 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2013 J9 INT J NANOMED JI Int. J. Nanomed. PY 2014 VL 9 BP 2179 EP 2190 DI 10.2147/IJN.S60937 PG 12 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA AG5GU UT WOS:000335448300001 PM 24855355 ER PT J AU Bertuccelli, G Marotta, F Zerbinati, N Cabeca, A He, F Jain, S Lorenzetti, A Yadav, H Milazzo, M Calabrese, F Tomella, C Catanzaro, R AF Bertuccelli, G. Marotta, F. Zerbinati, N. Cabeca, A. He, F. Jain, S. Lorenzetti, A. Yadav, H. Milazzo, M. Calabrese, F. Tomella, C. Catanzaro, R. TI IRON SUPPLEMENTATION IN YOUNG IRON-DEFICIENT FEMALES CAUSES GASTROINTESTINAL REDOX IMBALANCE: PROTECTIVE EFFECT OF A FERMENTED NUTRACEUTICAL SO JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS LA English DT Article DE Fermented papaya preparation; iron supplementation; oxidative stress; young females ID LIPID-PEROXIDATION; PAPAYA PREPARATION; FERROUS SULFATE; STRESS; WOMEN; OVERLOAD; DAMAGE; DNA AB The aim of this study was to assess whether the concomitant supplementation of certified fermented papaya preparation (FPP, ORI, Gifu, Japan) together with iron supplementation could beneficially affect lipid peroxidation either systemically and at a intraluminal gut level in women with low iron stores. Treatment compliance and iron absorption was assessed as well. Fifty-two non-pregnant, fertile, non-smokers, healthy women with iron deficiency were recruited. The women were given iron supplements (100 mg Fe/d as ferrous sulfate) to be taken daily for 12 weeks (group A). Group B patients were also supplemented with 6g/day of a FPP. A detailed life style questionnaire was administered to all subjects. Iron, ferritin, transferrin receptors (Tf R) and malondialdehyde (MDA) in plasma were measured. The RBCs lysate was used for the estimation of superoxide dismutase (SOD) and glutathione peroxidase (GPx). The total and free iron concentration as well as analysis of oxidative stress in the feces was measured. FPP-supplemented subjects showed a significantly lower degree of gastrointestinal discomfort (p<0.05) and abolished the iron supplementation-induced increase of MDA (p<0.001) and the depletion of SOD and GPx (p<0.01). Moreover, the nutraceutical co-administration brought about a significant reduction of gut oxidative damage and lower fecal content of either total and free iron (p<0.05 vs group A). Overall, group B showed a better TIR/ferritin ratio response (p<0.05 vs group A). While iron supplementation maintains its clinical relevance considering the prevalence of iron deficiency among females, a careful clinical evaluation and a protective nutraceutical co-administration, as our data suggest with FPP, should be considered. C1 [Bertuccelli, G.; Marotta, F.; Lorenzetti, A.; Tomella, C.] ReGenera Res Grp Aging Intervent, Milan, Italy. [Zerbinati, N.; Yadav, H.] CMP Med Ctr & Labs, Pavia, Italy. [Cabeca, A.] Prevent & Funct Med Ctr Brunswick, Brunswick, GA USA. [He, F.] Sichuan Univ, West China Sch Publ Hlth, Dept Nutr & Food Hyg, Chengdu, Sichuan, Peoples R China. [Jain, S.] NIDDK, NIH, Bethesda, MD 20892 USA. [Milazzo, M.; Calabrese, F.; Catanzaro, R.] Univ Catania, Dept Internal Med, Gastroenterol Unit, Catania, Italy. RP Marotta, F (reprint author), Res Grp Aging Intervent, Piazza Firenze 12, I-20154 Milan, Italy. EM fmarchimede@libero.it OI ZERBINATI, NICOLA/0000-0003-2177-9677 NR 31 TC 1 Z9 1 U1 0 U2 2 PU BIOLIFE SAS PI SILVA MARINA (TE) PA VIA S STEFANO 39 BIS, 64029 SILVA MARINA (TE), ITALY SN 0393-974X EI 1724-6083 J9 J BIOL REG HOMEOS AG JI J. Biol. Regul. Homeost. Agents PD JAN-MAR PY 2014 VL 28 IS 1 BP 53 EP 63 PG 11 WC Endocrinology & Metabolism; Immunology; Medicine, Research & Experimental; Physiology SC Endocrinology & Metabolism; Immunology; Research & Experimental Medicine; Physiology GA AG0RN UT WOS:000335123400006 PM 24750791 ER PT J AU Ucar-Comlekoglu, D Fox, A Sen, HN AF Ucar-Comlekoglu, Didar Fox, Austin Sen, H. Nida TI Gender Differences in Behcet's Disease Associated Uveitis SO JOURNAL OF OPHTHALMOLOGY LA English DT Review ID DOUBLE-BLIND TRIAL; CLINICAL-FEATURES; NEUROLOGICAL INVOLVEMENT; VASCULAR INVOLVEMENT; MUCOCUTANEOUS LESIONS; DEDICATED CENTER; MANIFESTATIONS; SEX; EPIDEMIOLOGY; CYCLOSPORINE AB Behcet's disease is a systemic vasculitis of unknown etiology, characterized by oral and genital ulceration, skin lesions, and uveitis as well as vascular, central nervous system, and gastrointestinal system involvement. It is prevalent in the Middle East, Mediterranean, and Eastern Asia. The aim of this review is to evaluate the gender differences in clinical manifestations of Behc,et's disease, treatment responses, mortality, and morbidity. Behcet's disease has been reported to be more prevalent in males from certain geographic regions and particular ethnic groups; however, recent reports indicate more even gender distribution across the world. There are gender differences in clinical manifestations and severity of the disease. Ocular manifestations, vascular involvement, and neurologic symptoms are more frequently reported in male patients whereas oral and genital ulcers, skin lesions, and arthritis occur more frequently in female patients. The disease can have a more severe course in males, and overall mortality rate is significantly higher among young male patients. C1 [Ucar-Comlekoglu, Didar; Fox, Austin; Sen, H. Nida] NEI, NIH, Bethesda, MD 20892 USA. [Ucar-Comlekoglu, Didar] Istanbul Univ, Cerrahpasa Med Fac, Dept Ophthalmol, TR-34080 Istanbul, Turkey. [Fox, Austin] Univ S Alabama, Coll Med, Mobile, AL 36688 USA. RP Sen, HN (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM senh@nei.nih.gov OI Comlekoglu, Erhan/0000-0002-0915-5821 FU NEI Intramural Research Program; National Institutes of Health (NIH) Medical Research Scholars Program; NIH; Foundation for the NIH from Pfizer Inc. FX This study has been sponsored by the NEI Intramural Research Program and this research was made possible through the National Institutes of Health (NIH) Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc., The Leona M. and Harry B. Helmsley Charitable Trust, and the Howard Hughes Medical Institute, as well as other private donors. For a complete list, please visit the foundation website at http://www.fnih.org/work/programs-development/medical-research-scholars- program. NR 77 TC 2 Z9 2 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-004X EI 2090-0058 J9 J OPHTHALMOL JI J. Ophthalmol. PY 2014 AR 820710 DI 10.1155/2014/820710 PG 8 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA AG3IT UT WOS:000335310000001 ER PT J AU Patrick, H AF Patrick, Heather TI Ascending Mount Maslow With Oxygen to Spare: A Self-Determination Theory Perspective SO PSYCHOLOGICAL INQUIRY LA English DT Editorial Material ID ROMANTIC RELATIONSHIPS; NEED FULFILLMENT; WELL; MINDFULNESS; MOTIVATION; HAPPINESS; BENEFITS; BEHAVIOR C1 NCI, Bethesda, MD 20892 USA. RP Patrick, H (reprint author), NCI, 9609 Med Ctr Dr,Room 3E112,MSC9761, Bethesda, MD 20892 USA. EM patrickha@mail.nih.gov NR 32 TC 2 Z9 2 U1 4 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1047-840X EI 1532-7965 J9 PSYCHOL INQ JI Psychol. Inq. PD JAN 1 PY 2014 VL 25 IS 1 BP 101 EP 107 DI 10.1080/1047840X.2014.878682 PG 7 WC Psychology, Multidisciplinary SC Psychology GA AE4EN UT WOS:000333934700012 ER PT J AU Sanderson, SC McBride, CM O'Neill, SC Docherty, S Shepperd, J Lipkus, IM AF Sanderson, S. C. McBride, C. M. O'Neill, S. C. Docherty, S. Shepperd, J. Lipkus, I. M. TI Young Smokers' Interpretations of the Estimated Lung Cancer Risk Associated with a Common Genetic Variant of Low Penetrance SO PUBLIC HEALTH GENOMICS LA English DT Article ID SMOKING-CESSATION; SUSCEPTIBILITY; COMMUNICATION; RESPONSES; GENOMICS; FEEDBACK; STUDENTS; BIAS C1 [Sanderson, S. C.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [McBride, C. M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [O'Neill, S. C.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Docherty, S.; Lipkus, I. M.] Duke Univ, Sch Nursing, Durham, NC USA. [Shepperd, J.] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. RP Sanderson, SC (reprint author), Icahn Sch Med Mt Sinai, 1425 Madison Ave,3rd Floor,Box 1498, New York, NY 10029 USA. EM saskia.sanderson@mssm.edu FU National Cancer Institute [R01 CA121922-01A2] FX This research was partially funded by a grant from the National Cancer Institute (R01 CA121922-01A2). NR 24 TC 0 Z9 0 U1 2 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 EI 1662-8063 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2014 VL 17 IS 2 BP 68 EP 75 DI 10.1159/000356708 PG 8 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA AG1WG UT WOS:000335206300002 PM 24556984 ER PT S AU Vemu, A Garnham, CP Lee, DY Roll-Mecak, A AF Vemu, Annapurna Garnham, Christopher P. Lee, Duck-Yeon Roll-Mecak, Antonina BE Vale, RD TI Generation of Differentially Modified Microtubules Using In Vitro Enzymatic Approaches SO RECONSTITUTING THE CYTOSKELETON SE Methods in Enzymology LA English DT Review; Book Chapter ID CHLAMYDOMONAS ALPHA-TUBULIN; BETA-TUBULIN; POSTTRANSLATIONAL MODIFICATIONS; STRUCTURAL BASIS; TYROSINE LIGASE; PLUS END; BRAIN; ACETYLTRANSFERASE; POLYGLUTAMYLATION; PURIFICATION AB Tubulin, the building block of microtubules, is subject to chemically diverse and evolutionarily conserved post-translational modifications that mark microtubules for specific functions in the cell. Here we describe in vitro methods for generating homogenous acetylated, glutamylated, or tyrosinated tubulin and microtubules using recombinantly expressed and purified modification enzymes. The generation of differentially modified microtubules now enables a mechanistic dissection of the effects of tubulin post-translational modifications on the dynamics and mechanical properties of microtubules as well as the behavior of motors and microtubule-associated proteins. C1 [Vemu, Annapurna; Garnham, Christopher P.; Roll-Mecak, Antonina] NINDS, Cell Biol & Biophys Unit, Bethesda, MD 20892 USA. [Lee, Duck-Yeon] NHLBI, Biochem Core, Bethesda, MD 20892 USA. [Roll-Mecak, Antonina] NHLBI, Ctr Biophys, Bethesda, MD 20892 USA. RP Roll-Mecak, A (reprint author), NINDS, Cell Biol & Biophys Unit, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM antonina@mail.nih.gov NR 42 TC 8 Z9 8 U1 0 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-397924-7 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2014 VL 540 BP 149 EP 166 DI 10.1016/B978-0-12-397924-7.00009-1 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA3DV UT WOS:000334128900010 PM 24630106 ER PT J AU Geller, NL Wu, CL AF Geller, Nancy L. Wu, Colin TI Gang Zheng (May 6, 1965 January 9, 2014) In memoriam SO STATISTICS AND ITS INTERFACE LA English DT Biographical-Item C1 [Geller, Nancy L.; Wu, Colin] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Geller, NL (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM gellern@nhlbi.nih.gov; wuc@nhlbi.nih.gov NR 1 TC 1 Z9 1 U1 0 U2 0 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2014 VL 7 IS 1 BP 3 EP 7 PG 5 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA AG0GX UT WOS:000335095000001 ER PT J AU Li, ZB Liu, AY Li, ZH Li, QH AF Li, Zhengbang Liu, Aiyi Li, Zhaohai Li, Qizhai TI Rank-based tests for comparison of multiple endpoints among several populations SO STATISTICS AND ITS INTERFACE LA English DT Article DE Max; Multidimensional outcomes; Rank-based statistics ID BEHRENS-FISHER PROBLEM AB We consider comparison of multiple endpoints among several independent populations. We extend O'Brien's and Huang et al.'s methods from comparison of two groups to two more groups, and propose three max type test statistics, T-1 based on normally distributed data, T-2 obtained from pairwise ranking, and T-3 derived from ranking of all populations. Numerical results show that all three test statistics maintain the desired type I error rates and achieve satisfactory power. When the normal assumption is justified, T1 is slightly more powerful than T2 and T3. However, when the normal assumption is violated, T2 and T3 gain sizable power. All three tests have higher power than O'Brien's and Huang et al.'s methods using Bonferroni correction under the considered settings. The methods are exemplified using healthy eating index data from a study examining the conformance to dietary guideline. C1 [Li, Zhengbang] Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China. [Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20052 USA. [Li, Zhaohai] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100190, Peoples R China. RP Li, QH (reprint author), Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100190, Peoples R China. EM lizhengbang@mail.ccnu.edu.com; lima@mail.nih.gov; zli@gwu.edu; liqz@amss.ac.cn OI Liu, Aiyi/0000-0002-6618-5082 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institutes of Health (NIH), USA; NNSFC [61134013] FX We thank Dr. Tonja Nansel for providing the dietary quality and nutrients intake data to exemplify the methods. Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), USA. Corresponding author. Partially supported by NNSFC, No. 61134013. NR 10 TC 2 Z9 2 U1 3 U2 5 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2014 VL 7 IS 1 BP 9 EP 18 PG 10 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA AG0GX UT WOS:000335095000002 ER PT J AU Hu, ZH Qin, J Follmann, DA AF Hu, Zonghui Qin, Jing Follmann, Dean A. TI Semiparametric mixture survival model with application to MRFIT study SO STATISTICS AND ITS INTERFACE LA English DT Article DE Censoring; Empirical likelihood; Exponential tilting; Inverse-censoring-probability weighting; Mixture distribution; Survival function ID FACTOR INTERVENTION TRIAL; EMPIRICAL LIKELIHOOD; PROPORTIONS; MORTALITY AB We study the mixture survival model where subject i has a probability pi following one survival distribution and 1- p(i) following the other. The two survival distributions are unspecified except for an exponential tilting between the failure densities. Semiparametric likelihood estimation is proposed to handle censoring through conditional likelihood and inverse-censoring-probability weighted likelihood. Though full likelihood estimation is introduced, it is not always preferred over the other estimations due to its computational complexity and that its improvement in efficiency depends on the pattern of censoring. In the motivating example MRFIT study, we apply mixture survival modeling to uncover the underlying survival patterns in the control arm: one for the would-be compliers and one for the would be non-compliers, where compliance of each subject is not observable but associated with a probability. C1 [Hu, Zonghui; Qin, Jing; Follmann, Dean A.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Hu, ZH (reprint author), NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. EM huzo@niaid.nih.gov; jqin@niaid.nih.gov; ollmann@niaid.nih.gov NR 18 TC 1 Z9 1 U1 0 U2 1 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2014 VL 7 IS 1 BP 19 EP 26 PG 8 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA AG0GX UT WOS:000335095000003 ER PT J AU Izmirlian, G AF Izmirlian, Grant TI Estimation of the relative risk following group sequential procedure based upon the weighted log-rank statistic SO STATISTICS AND ITS INTERFACE LA English DT Article DE Weighted log-rank statistic; Group sequential; Interim analysis; Estimation ID DESIGN; TRIAL AB This paper considers a group sequentially monitored trial on a survival endpoint, monitored using a weighted log-rank (WLR) statistic with bounded weight function. Results and discussion center on the theoretical and practical concerns encountered in this setting. We demonstrate the construction of Lan Demets boundaries and calculation of design adjusted p-values and confidence intervals. Central to this discussion is a bijection which exists between the weighted log-rank statistic and a weighted averaged logged relative risk which is shown to exist when there is no sign change in the weighting function. We also show under parametric assumptions that the bijection can be estimated at each interim analysis. The results are benchmarked in a simulation study and a section is devoted to the decisions made in applying the methods to monitoring in the the National Lung Screening Trial (NLST). C1 Natl Natl Canc Inst, Canc Prevent Div, Biometry Res Grp, Bethesda, MD 20892 USA. RP Izmirlian, G (reprint author), Natl Natl Canc Inst, Canc Prevent Div, Biometry Res Grp, BG 9609 RM 5E130 MSC 9789 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM izmirlig@mail.nih.gov NR 14 TC 1 Z9 1 U1 0 U2 4 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2014 VL 7 IS 1 BP 27 EP 42 PG 16 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA AG0GX UT WOS:000335095000004 ER PT J AU Yuan, A Li, QZ Qin, J Zheng, G AF Yuan, Ao Li, Qizhai Qin, Jing Zheng, Gang TI Estimation of genetic effects incorporating prior information SO STATISTICS AND ITS INTERFACE LA English DT Article DE Asymptotics; Bayesian analysis; Case-control genetic study; Hybrid inference; Loss function; Power prior; Prospective and retrospective ID REGRESSION-MODELS; ASSOCIATION AB We study estimations of the genetic effect of a marker by adjusting out covariates and incorporating the results of previous potentially heterogenous studies of the same genetic marker. Without prior information on the covariates, the procedures are based on both frequentist and Bayesian methods by simultaneously maximizing the likelihood function for the coefficients of the covariates and minimizing the loss function for the genetic effect, and hence are regarded as hybrid estimations. Although we focus on an application to case-control genetic association studies, we describe a general method for various types of traits. For the application, we show that the proposed hybrid inference based on the prospective sampling can be applied to retrospectively collected case-control data. Simulations and applications using hybrid inference are presented. C1 [Yuan, Ao] Howard Univ, Natl Human Genome Ctr, Stat Genet & Bioinformat Unit, Washington, DC 20059 USA. [Li, Qizhai] Acad Sci, Acad Math & Syst Sci, Beijing, Peoples R China. [Qin, Jing] NHLBI, Biostat Res Branch, Bethesda, MD 20892 USA. [Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. EM ayuan@howard.edu; liqz@amss.ac.cn; jingqin@niaid.nih.gov; zhengg@nhlbi.nih.gov FU National Institute on Minority Health; Health Disparities of the National Institutes of Health [G12MD007597]; National Nature Science Foundation of China [61134013] FX Partially supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Number G12MD007597.; Partially supported by National Nature Science Foundation of China, No. 61134013. NR 17 TC 0 Z9 0 U1 2 U2 3 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2014 VL 7 IS 1 BP 43 EP 50 PG 8 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA AG0GX UT WOS:000335095000005 ER PT J AU Lobach, I Fan, RZ Manga, P AF Lobach, Iryna Fan, Ruzong Manga, Prashiela TI Genotype-based association models of complex diseases to detect gene-gene and gene-environment interactions SO STATISTICS AND ITS INTERFACE LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISMS; QUANTITATIVE TRAIT LOCI; HUMAN-SKIN; OCULOCUTANEOUS ALBINISM; HAPLOTYPE MAP; HUMAN GENOME; WOMEN; ALCOHOLISM; MELANOMA; DEPENDENCE AB A central problem in genetic epidemiology is to identify and rank genetic markers involved in a disease. Complex diseases, such as cancer, hypertension, diabetes, are thought to be caused by an interaction of a panel of genetic factors, that can be identified by markers, which modulate environmental factors. Moreover, the effect of each genetic marker may be small. Hence, the association signal may be missed unless a large sample is considered, or a priori biomedical data are used. Recent advances generated a vast variety of a priori information, including linkage maps and information about gene regulatory dependence assembled into curated pathway databases. We propose a genotype-based approach that takes into account linkage disequilibrium (LD) information between genetic markers that are in moderate LD while modeling gene-gene and gene-environment interactions. A major advantage of our method is that the observed genetic information enters a model directly thus eliminating the need to estimate haplotype-phase. Our approach results in an algorithm that is inexpensive computationally and does not suffer from bias induced by haplotype-phase ambiguity. We investigated our model in a series of simulation experiments and demonstrated that the proposed approach results in estimates that are nearly unbiased and have small variability. We applied our method to the analysis of data from a melanoma case-control study and investigated interaction between a set of pigmentation genes and environmental factors defined by age and gender. Furthermore, an application of our method is demonstrated using a study of Alcohol Dependence. C1 [Lobach, Iryna] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94185 USA. [Fan, Ruzong] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA. [Manga, Prashiela] NYU, Sch Med, Ronald O Perelman Dept Dermatol, New York, NY 10016 USA. RP Lobach, I (reprint author), Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94185 USA. EM ilobach@memory.ucsf.edu; ruzong.fan@nih.gov; prashiela.manga@nyumc.org FU National Cancer Institute [5P30CA16087-28]; National Institutes of Health (NIH) Maryland, USA.; New York University Langone Medical Center; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) FX The research was supported by the National Cancer Institute grant 5P30CA16087-28 and New York University Langone Medical Center, Center of Excellence 'Cancers of the Skin' pilot project. Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Maryland, USA. NR 36 TC 0 Z9 0 U1 3 U2 8 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2014 VL 7 IS 1 BP 51 EP 60 PG 10 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA AG0GX UT WOS:000335095000006 PM 26191336 ER PT J AU Li, QZ Xiong, WJ Chen, JB Zheng, G Li, ZH Mills, JL Liu, AY AF Li, Qizhai Xiong, Wenjun Chen, Jinbo Zheng, Gang Li, Zhaohai Mills, James L. Liu, Aiyi TI A robust test for quantitative trait analysis with model uncertainty in genetic association studies SO STATISTICS AND ITS INTERFACE LA English DT Article DE F-test; Robust; Quantitative trait; Genome-wide association studies ID GENOME-WIDE ASSOCIATION; POPULATION STRATIFICATION; NUISANCE PARAMETER; SCANS AB Statistical tests that assume an additive model are commonly employed in genetic association studies. However, the true models for genetic variants are rarely known. A mis-specified genetic model may lead to loss of power in identifying the potential markers associated with a disease. In this paper, we develop a robust test based on modified F-test statistics for quantitative trait genetic association studies and a simple method to compute its statistical significance and power. We also study sample size calculations for designing such an association study. Numerical results, including simulation studies and a real data example, show that the proposed robust test has satisfactory performance when the model is unknown and is more robust than some existing procedures when the model is mis-specified. C1 [Li, Qizhai; Xiong, Wenjun] Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100190, Peoples R China. [Chen, Jinbo] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Zheng, Gang] Natl Heart Lung & Blood Inst, Off Biostat Res, Bethesda, MD 20892 USA. [Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20052 USA. [Mills, James L.; Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Liu, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. EM liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 FU NICHD [NO1-HD3-3348]; NHGRI; Health Research Board Ireland; National Science Foundation of China [10901155, 61134013]; National Institutes of Health (NIH) [R01ES016626]; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) FX The design,recruitment,and all metabolite and genomic analyses of the TSS cohort were implemented through the collaboration of Prof,John Scott and Dr.Anne Molloy Trinity College Dublin,Ireland,Dr. Pendar Kirke,Health Research Board,Dublin,Ireland,Dr.Lawrence Brody and Dr. Faith Pangilinan, National Human Genome Research Institute (NHGRI) and Dr. James Mills, Eunice Shriver National Institute for Child Health and Human Development (NICHD) with funding through NICHD contract NO1- HD3-3348 and with additional financial support from NHGRI and the Health Research Board, Ireland. The work was supported in part by National Science Foundation of China (Grant No. 10901155, 61134013), the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institutes of Health (NIH) and NIH grant: R01ES016626. NR 19 TC 0 Z9 0 U1 0 U2 7 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2014 VL 7 IS 1 BP 61 EP 68 PG 8 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA AG0GX UT WOS:000335095000007 ER PT J AU Wright, GW Dodd, LE Korn, EL AF Wright, George W. Dodd, Lori E. Korn, Edward L. TI Inherent difficulties in nonparametric estimation of the cumulative distribution function using observations measured with error: Application to high-dimensional microarray data SO STATISTICS AND ITS INTERFACE LA English DT Article DE Empirical Bayes; Stability; Microarray Data; Mixture Models; Measurement Error; Shrinkage ID BAYES ESTIMATION; EMPIRICAL BAYES AB Distribution function estimation is important in many biological applications. A very simple example is given to show that with the addition of normal errors, data from very different underlying distributions can generate nearly identical distributions of observations. Therefore, in some situations it can be essentially impossible to accurately estimate an underlying cumulative distribution function from a reasonable number of observations measured with error. An application is given involving estimating the distribution function of differential gene expression based on more than fifty thousand genes. C1 [Wright, George W.; Korn, Edward L.] NCI, Biometr Res Branch, MSC 9735, Bethesda, MD 20892 USA. [Dodd, Lori E.] Natl Inst Allergy & Infect Dis, Bethesda, MD 20817 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, MSC 9735, Bethesda, MD 20892 USA. EM wrightge@mail.nih.gov; doddl@mail.nih.gov; korne@ctep.nci.nih.gov NR 21 TC 0 Z9 0 U1 0 U2 2 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2014 VL 7 IS 1 BP 69 EP 73 PG 5 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA AG0GX UT WOS:000335095000008 ER PT J AU Tian, X Wu, CO AF Tian, Xin Wu, Colin O. TI Estimation of rank-tracking probabilities using nonparametric mixed-effects models for longitudinal data SO STATISTICS AND ITS INTERFACE LA English DT Article DE Basis approximation; Conditional distribution; Longitudinal study; Mixed model; Time-varying coefficient model; Rank-tracking probability ID VARYING-COEFFICIENT MODELS; CARDIOVASCULAR-DISEASE; RISK-FACTORS; GROWTH; CHILDHOOD; HEALTH; GIRLS AB An important scientific objective of longitudinal studies involves tracking the probability of a subject having certain health status over the course of the study. Proper definitions and estimates of disease risk tracking have important implications in the design and analysis of long-term biomedical studies and in developing guidelines for disease prevention and intervention. We study in this paper a class of "rank-tracking probabilities" (RTP) to describe a sub-ject's conditional probabilities of having certain health outcomes at two different time points. Structural nonparametric estimation and inferences for the RTPs and their functions are developed based on nonparametric mixed-effects models and B-spline smoothing methods. Statistical properties of our procedures are investigated through a simulation study. We apply our methods to an epidemiological study of childhood cardiovascular risk factors, and demonstrate that the RTPs and their nonparametric estimators provide useful tools to quantitatively evaluate whether the cardiovascular risks, such as obesity and hypertension, can be tracked from early childhood to adolescence. C1 [Tian, Xin; Wu, Colin O.] Natl Heart Lung & Blood Inst, Off Biostat Res, Bethesda, MD 20892 USA. RP Tian, X (reprint author), Natl Heart Lung & Blood Inst, Off Biostat Res, Bethesda, MD 20892 USA. EM tianx@nhibi.nih.gov FU National Heart, Lung and Blood Institute [N01-HC-55023-26, U01-HL48941-44] FX The authors would like to thank Drs. Eric Leifer and Dihua Xu for reviewing the initial draft, and Drs. Eva Obarzanek, Stephen R. Daniels, Rae-Ellen W. Kavey, Gail D. Pearson, and Jeffrey A. Cutler for explaining the importance of "rank-tracking" in pediatric studies and the objectives of the National Growth and Health Study. The National Growth and Health Study was supported by contracts #N01-HC-55023-26 and grants #U01-HL48941-44 from the National Heart, Lung and Blood Institute. NR 21 TC 1 Z9 1 U1 0 U2 0 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2014 VL 7 IS 1 BP 87 EP 99 PG 13 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA AG0GX UT WOS:000335095000010 ER PT J AU Yu, BB O'Malley, AJ Ghosh, P AF Yu, Binbing O'Malley, A. James Ghosh, Pulak TI Linear mixed models for multiple outcomes using extended multivariate skew-t distributions SO STATISTICS AND ITS INTERFACE LA English DT Article DE Multivariate skew-t; Robust method; Scale-mixture representation ID RANDOM-EFFECTS MISSPECIFICATION; LONGITUDINAL DATA; ELLIPTIC DISTRIBUTIONS; BAYESIAN-ANALYSIS; II ERROR; INFERENCE; TRANSFORMATION; POPULATION; FREEDOM; COUNT AB Multivariate outcomes with heavy skewness and thick tails often arise from clustered experiments or longitudinal studies. Linear mixed models with multivariate skew-t (MST) distributions for the random effects and the error terms is a popular tool of robust modeling for such outcomes. However the usual MST distribution only allows a common degree of freedom for all marginal distributions, which is only appropriate when each marginal has the same amount of tail heaviness. In this paper, we introduce a new class of extended MST distributions, which allow different degrees of freedom and thereby can accommodate heterogeneity in tail-heaviness across outcomes. The extended MST distributions yield a flexible family of models for multivariate outcomes. The hierarchical representation of the MST distribution allows MCMC methods to be easily applied to compute the parameter estimates. The proposed model is applied to data from two biomedical studies: one on bivariate markers of AIDS progression and the other on sexual behavior from a longitudinal study. C1 [Yu, Binbing] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20904 USA. [O'Malley, A. James] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Ghosh, Pulak] Indian Inst Management, Dept Quantitat Methods & Informat Sci, Bangalore 560076, Karnataka, India. RP Yu, BB (reprint author), NIA, Lab Epidemiol & Populat Sci, 7201 Wisconsin Ave Suite 3C309, Bethesda, MD 20904 USA. EM whybb@yahoo.com; omalley@hcp.med.harvard.edu; pulakghoshc@gmail.com FU Intramural Research Program of the National Institute on Aging FX The research was supported in part by the Intramural Research Program of the National Institute on Aging. The computation utilized the high-performance computational capabilities of the Biowulf PC/Linux cluster at the National Institutes of Health, Bethesda, Maryland, USA NR 48 TC 2 Z9 2 U1 1 U2 6 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2014 VL 7 IS 1 BP 101 EP 111 PG 11 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA AG0GX UT WOS:000335095000011 ER PT J AU Chen, Z Xie, YL AF Chen, Zhen Xie, Yunlong TI Marginal analysis of measurement agreement among multiple raters with non-ignorable missing ratings SO STATISTICS AND ITS INTERFACE LA English DT Article DE Fleiss k; Scott pi; Within-cluster resampling; Marginal approach ID CLUSTERED DATA; RELIABILITY; SIZE; INTERRATER C1 [Chen, Zhen; Xie, Yunlong] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA. RP Chen, Z (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA. EM chenzhe@mail.nih.gov; yunlong.xie@nih.gov FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX We thank the Center for Information Technology, the National Institutes of Health, for providing access to the high performance computational capabilities of the Biowulf cluster. This research was supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 14 TC 0 Z9 0 U1 0 U2 3 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2014 VL 7 IS 1 BP 113 EP 120 PG 8 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA AG0GX UT WOS:000335095000012 ER PT J AU Zhu, L Pickle, LW Zou, ZH Cucinelli, J AF Zhu, Li Pickle, Linda W. Zou, Zhaohui Cucinelli, James TI Trends and patterns of childhood cancer incidence in the United States, 1995-2010 SO STATISTICS AND ITS INTERFACE LA English DT Article DE Childhood cancer; Incidence; Projection method; Joinpoint regression; Spatial pattern; Temporal trend ID TUMORS; BRAIN; RATES AB Background: The American dancer Society publishes Cancer Facts & Figures every year to provide estimated incidence rates and case counts for the current calendar year. Childhood cancer (children aged 0-14 with all cancer) incidence was also estimated and reported in Cancer Facts & Figures, but there is no report on patients in the 15-19 years of age or combined 0-19 years of age, or on major childhood cancers such as leukemia. There may be different effects of socioeconomic status and geography on childhood cancer in comparison to cancer in adults. Therefore, models used to predict cancer case counts for all patients may need to be modified to accurately evaluate and predict incidence rates of childhood cancers. Methods: The original method was developed in 2007 to project the total cancer incidence counts reported in the Cancer Facts & Figures. This method requires first a spatiotemporal prediction across the extensive years of data since not all cancer registries have data for every year, and secondly a 4-year temporal projection from the most current data point to the current calendar year. Here we use this same process applied only to childhood cancer data. The generalized linear mixed effects model is applied to observed childhood cancer case counts reported to the North American Association of Central Cancer Registries over 1995 2006 to predict case counts and incidence rates for every U.S. state and the U.S. total (for patients aged 0 to 19 and for major cancers among childhood). Covariates included in the model are measures of income, education, housing, urban/rural status, health insurance coverage, smoking, obesity and cancer screening. Temporal trends and spatial distribution patterns are compared among childhood cancers for males and females. Results: A total of 15,168 new cancer cases was projected for the 0-19 age group, with 10,032 childhood cancer cases younger than age 15, and 5,136 cases in the 15-19 age group, in the U.S. for 2010. There are more male cancer cases than female cases in all three age groups for most cancer sites. children differs by age group and sex. The study also identifies differences in the geograhic patterns at a small geographic area level by gender and temporal trends by gender and subsites of childhood cancer incidence. Conclusions: The resulting set of predictions provides annual estimates for states that did not provide data at all, and projections ahead in time to the current calendar year for every U.S. state and the U.S. in total. These projections fill in the data gaps for recent years of diagnosis and state registries to provide complete count and rate estimates for childhood cancers for all states, regions, and the U.S. in total C1 [Zhu, Li] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Pickle, Linda W.] StatNet Consulting LLC, Gaithersburg, MD 20879 USA. [Zou, Zhaohui; Cucinelli, James] Information Management Serv Inc, Silver Spring, MD 20904 USA. RP Zhu, L (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. EM li.zhu@nih.gov; linda@statnetconsulting.com; zouj@imsweb.com; cucinellij@imsweb.com NR 28 TC 2 Z9 2 U1 0 U2 11 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2014 VL 7 IS 1 BP 121 EP 134 PG 14 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA AG0GX UT WOS:000335095000013 ER PT J AU Chen, HS Mariotto, AB Zhu, L Kim, HJ Cho, H Feuer, EJ AF Chen, Huann-Sheng Mariotto, Angela B. Zhu, Li Kim, Hyune-Ju Cho, Hyunsoon Feuer, Eric J. TI Developments and challenges in statistical methods in cancer surveillance SO STATISTICS AND ITS INTERFACE LA English DT Article DE Cancer surveillance; Joinpoint regression model; Delay adjustment model; Survival analysis; Spatial statistics; Incidence; Mortality; Prevalence ID POPULATION-BASED CANCER; CURRENT CALENDAR YEAR; RELATIVE SURVIVAL ANALYSIS; SEGMENTED LINE REGRESSION; LONG-TERM SURVIVAL; UNITED-STATES; REGISTRY DATA; INTERPRETING TRENDS; PROSTATE-CANCER; REPORTING-DELAY AB Cancer surveillance includes the monitoring of population levels and trends in incidence, survival, mortality, and prevalence. In addition, data are collected on the factors that influence these basic statistics across the entire cancer control continuum, such as healthy populations at risk of cancer, new diagnosis of cancer, treatment of cancer, living with cancer, and dying of cancer or other causes. To interpret the cancer statistics that are collected, an entire area of statistical methodology has been developed at the U.S. National Cancer Institute (NCI) and other institutions throughout the world. Most of these developments took place in the last 20 years, and the field is still evolving. In this review, we provide an overview of these methods, including the motivation for their development and how the methods compare with more general mainstream statistical methodology; available software; and relevant literature references. C1 [Chen, Huann-Sheng; Mariotto, Angela B.; Zhu, Li; Cho, Hyunsoon; Feuer, Eric J.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Kim, Hyune-Ju] Syracuse Univ, Dept Math, Syracuse, NY 13244 USA. RP Chen, HS (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. EM Huann-Sheng.Chen@nih.gov; mariotta@mail.nih.gov; Li.Zhu@nih.gov; hjkim@syr.edu; hscho@ncc.re.kr; feuerr@mail.nih.gov NR 97 TC 0 Z9 0 U1 3 U2 9 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2014 VL 7 IS 1 BP 135 EP 151 PG 17 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA AG0GX UT WOS:000335095000014 ER PT J AU She, DW Zhang, H Li, Y Graubard, BI Li, ZH AF She, Dewei Zhang, Hong Li, Yan Graubard, Barry I. Li, Zhaohai TI Family based association study with complex survey data SO STATISTICS AND ITS INTERFACE LA English DT Article DE Complex sampling; Conditional likelihood score test; Nuclear family; Survey data; Trend test ID TRANSMISSION DISEQUILIBRIUM TEST; HARDY-WEINBERG EQUILIBRIUM; SAMPLE-SIZE; REGRESSION-COEFFICIENTS; LINKAGE DISEQUILIBRIUM; GENETIC ASSOCIATION; NUCLEAR FAMILIES; TREND TESTS; POWER; SUBDIVISION AB Genetic data collected from the Third National Health and Nutrition Examination Survey (NHANES III) provides an opportunity to investigate associations between genetic variations and health-related phenotypes for the US population. Complex sample designs involving stratified multistage cluster sampling and sample weighting are used to sample families in household surveys such as the NHANES III. We modified conditional likelihood score and trend tests used to test the null hypothesis of no association between a candidate gene and a phenotype in simple random samples of nuclear families so that these tests are applicable to data from complex sample designs. The finite sample properties of our modified test procedures are evaluated via Monte Carlo simulation studies. We recommend using an F-version of the trend test instead of a score test because the F-test shows greater power. Our test statistics are applied to NHANES III data to test for associations between the locus ADRB2 (rs1042713) and obesity, VDR (rs2239185) and high blood lead level, and TGFB1 (rs1982073) and asthma. C1 [She, Dewei; Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20052 USA. [Zhang, Hong] Fudan Univ, Inst Biostat, Sch Life Sci, Shanghai 200433, Peoples R China. [Zhang, Hong; Graubard, Barry I.; Li, Zhaohai] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20852 USA. [Li, Yan] Univ Texas Arlington, Dept Math, Arlington, TX 76019 USA. [Li, Yan] Univ Maryland, Joint Program Survey Methodol, College Pk, MD 20742 USA. RP Li, ZH (reprint author), George Washington Univ, Dept Stat, Washington, DC 20052 USA. EM zli@gwu.edu FU NIH grant [RO1ES016626]; NSFC grant [11371101] FX The authors thank Mr. Christopher Sanders and Dr. Geraldine McQuillan from National Center for Health Statistics, Centers for Disease Control and Prevention for preparing the NHANES III genetic data for us. The work was partially supported by an NIH grant (No. RO1ES016626, Zhaohai Li) and an NSFC grant (No. 11371101, Hong Zhang and Zhaohai Li). NR 29 TC 0 Z9 0 U1 3 U2 5 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2014 VL 7 IS 2 BP 167 EP 176 PG 10 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA AG4KM UT WOS:000335388500002 ER PT J AU Domingues, CEF Olivera, CMC Oliveira, BV Juste, FS Andrade, CRF Giacheti, CM Moretti-Ferreira, D Drayna, D AF Domingues, C. E. F. Olivera, C. M. C. Oliveira, B. V. Juste, F. S. Andrade, C. R. F. Giacheti, C. M. Moretti-Ferreira, D. Drayna, D. TI A genetic linkage study in Brazil identifies a new locus for persistent developmental stuttering on chromosome 10 SO GENETICS AND MOLECULAR RESEARCH LA English DT Article DE Stuttering; Linkage; Dominant; Chromosome 10q ID TWIN; ETIOLOGY; SAMPLE AB Although twin, adoption, and family studies demonstrate that genetic factors are involved in the origins of stuttering, the mode of transmission of the disorder in families is not well defined and stuttering is considered a genetically complex trait. We performed a genome-wide linkage scan in a group of 43 Brazilian families, each containing multiple cases of persistent developmental stuttering. Linkage analysis under a dominant model of inheritance generated significant evidence of linkage in two Brazilian families, with a combined maximum single-point LOD score of 4.02 and a multipoint LOD score of 4.28 on chromosome 10q21. This demonstrated the presence of a novel variant gene at this locus that predisposes individuals to stuttering, which provides an opportunity to identify novel genetic mechanisms that underlie this disorder. C1 [Domingues, C. E. F.; Drayna, D.] NIDCD, NIH, Rockville, MD 20850 USA. [Domingues, C. E. F.; Oliveira, B. V.; Moretti-Ferreira, D.] Univ Estadual Paulista, Inst Biociencias Botucatu, Dept Genet, Botucatu, SP, Brazil. [Olivera, C. M. C.; Giacheti, C. M.] Univ Estadual Paulista, Dept Fonoaudiol, Ctr Estudos Educ & Saude, Marilia, SP, Brazil. [Juste, F. S.; Andrade, C. R. F.] Univ Sao Paulo, Dept Fonoaudiol Fisioterapia & Terapia Ocupac, Fac Med, Sao Paulo, SP, Brazil. RP Drayna, D (reprint author), NIDCD, NIH, Rockville, MD 20850 USA. EM drayna@nidcd.nih.gov RI Juste, Fabiola/B-3544-2015; Giacheti, Celia/I-4863-2012 OI Juste, Fabiola/0000-0002-2882-9895; Giacheti, Celia/0000-0001-9691-4672 FU National Institute on Deafness and Other Communication Disorders/National Institutes of Health Intramural [Z01-000046-12]; Coordination for the Improvement of Higher Education Personnel (CAPES) foundation, Brazil FX Research supported by the National Institute on Deafness and Other Communication Disorders/National Institutes of Health Intramural (Grant #Z01-000046-12), and by the Coordination for the Improvement of Higher Education Personnel (CAPES) foundation, Brazil (C. E. F. Domingues). We thank M. Hashim Raza, Eduardo Sainz, Alejandro Schaffer, Thomas Friedman, and Andrew Griffith for technical guidance and comments on the manuscript, and the family members who participated in this research study. NR 28 TC 4 Z9 5 U1 1 U2 7 PU FUNPEC-EDITORA PI RIBEIRAO PRETO PA RUA FLORIANO PEIXOTO 2444, ALTO DA BOA VISTA, RIBEIRAO PRETO, SP 00000, BRAZIL SN 1676-5680 J9 GENET MOL RES JI Genet. Mol. Res. PY 2014 VL 13 IS 1 BP 2094 EP 2101 DI 10.4238/2014.March.24.13 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AE6PA UT WOS:000334114800133 PM 24737434 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI RESTARTING DNA REPLICATION BY RECOMBINATION SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 1 EP 12 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900002 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI Genome Stability DNA Repair and Recombination PREFACE SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Editorial Material; Book Chapter C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP V EP VIII PG 4 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900001 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI DOUBLE-STRAND BREAK REPAIR PATHWAYS SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter ID RECOMBINATION C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 13 EP 17 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900003 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI RecA/Rad51 AND THE SEARCH FOR HOMOLOGY SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter ID RECA; DNA; RECOMBINATION C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 2 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 19 EP 44 PG 26 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900004 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI PREPARATION OF THE RecA/Rad51 FILAMENT SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter ID DOUBLE-STRAND BREAK; RAD51-MEDIATED RECOMBINATION; DNA-REPAIR; BRCA2; REVEALS C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 45 EP 72 PG 28 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900005 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI SINGLE-STRAND ANNEALING SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter ID BREAK REPAIR; PATHWAY C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 73 EP 87 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900006 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI GENE CONVERSION SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter ID DOUBLE-STRAND BREAKS; GAP REPAIR; RECOMBINATION; MODEL; DNA; DROSOPHILA C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 1 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 89 EP 125 PG 37 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900007 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI "IN VIVO BIOCHEMISTRY": RECOMBINATION IN YEAST SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter ID DOUBLE-STRAND BREAK; MATING-TYPE; FISSION YEAST; SACCHAROMYCES-CEREVISIAE; HOMOLOGOUS RECOMBINATION; DNA STRANDS; REPAIR; CHOICE C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 127 EP 160 PG 34 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900008 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI BREAK-INDUCED REPLICATION SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter ID DNA-REPLICATION; RECOMBINATION; FORKS C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 1 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 161 EP 194 PG 34 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900009 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI SISTER CHROMATID REPAIR SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter ID DEINOCOCCUS-RADIODURANS; MAMMALIAN-CELLS; RECOMBINATION; RESISTANCE; MECHANISMS; PATHWAYS; EXCHANGE C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 195 EP 213 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900010 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI GENE TARGETING SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter ID GENOME; RECOMBINATION; YEAST C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 1 U2 1 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 215 EP 241 PG 27 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900011 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI SITE-SPECIFIC RECOMBINATION SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter ID DROSOPHILA C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 243 EP 254 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900012 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI CYTOLOGY AND GENETICS OF MEIOSIS SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter ID MEIOTIC CROSSING-OVER; STRAND BREAK REPAIR; SACCHAROMYCES-CEREVISIAE; RECOMBINATION; INTERFERENCE; CONVERSION; ELEGANS; MODEL C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 16 TC 0 Z9 0 U1 1 U2 1 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 255 EP 286 PG 32 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900013 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI MOLECULAR EVENTS DURING MEIOTIC RECOMBINATION SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter ID DOUBLE-STRAND BREAKS; MITOTIC RECOMBINATION; MEIOSIS; YEAST; DNA; RESOLUTION C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 17 TC 0 Z9 0 U1 2 U2 2 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 287 EP 332 PG 46 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900014 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI HOLLIDAY JUNCTION RESOWASES AND CROSSING OVER SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter ID RESOLUTION C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 333 EP 351 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900015 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI NONHOMOLOGOUS END-JOINING SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter ID STRAND BREAK REPAIR; DNA C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 353 EP 366 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900016 ER PT B AU Haber, JE AF Haber, James E. BA Hager, JE BF Hager, JE TI DNA DAMAGE CHECKPOINTS AND GENOME INSTABILITY SO GENOME STABILITY: DNA REPAIR AND RECOMBINATION LA English DT Article; Book Chapter ID DOUBLE-STRAND BREAKS; CANCER C1 [Haber, James E.] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU GARLAND SCIENCE, TAYLOR & FRANCIS PI NEW YORK PA 270 MADISON AVENUE, NEW YORK, NY 10016 USA BN 978-0-8153-4485-8 PY 2014 BP 367 EP 381 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA BA0CY UT WOS:000331019900017 ER PT S AU Pazdrak, K Kurosky, A AF Pazdrak, Konrad Kurosky, Alexander BE Brasier, AR TI Functional Proteomics for the Characterization of Impaired Cellular Responses to Glucocorticoids in Asthma SO HETEROGENEITY IN ASTHMA SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Steroid resistance; Glucocorticoids; Proteomics; Asthma; Mass spectrometry; Cell signaling pathways; Biomarkers; Eosinophils; Airway inflammatory cells; Phosphoproteomics ID RECEPTOR-BINDING AFFINITY; COLONY-STIMULATING FACTOR; SPUTUM EOSINOPHIL COUNTS; PROTEIN PHOSPHATASE 5; STEROID RESISTANCE; INDUCED APOPTOSIS; BRONCHIAL-ASTHMA; GENE-EXPRESSION; T-LYMPHOCYTES; IN-VIVO AB In chronic airway inflammatory disorders, such as asthma, glucocorticoid (GC) insensitivity is a challenging clinical problem associated with life-threatening disease progression and the potential development of serious side effects. The mechanism of steroid resistance in asthma remains unclear and may be multifactorial. Excluding noncompliance with GC treatment, abnormal steroid pharmacokinetics, and rare genetic defects in the glucocorticoid receptor (GR), the majority of GC insensitivity in asthma can be attributed to secondary defects related to GR function. Airway inflammatory cells obtained from patients with GC-resistant asthma show a number of abnormalities in cell immune responses to GC, which suggests that there is a causative defect in GR signaling in GC-resistant cells that could be further elucidated by a functional and molecular proteomics approach. Since T cells, eosinophils, and monocytes play a major role in the pathogenesis of airway inflammation, most of the work published to date has focused on these cell types as the primary therapeutic targets in GC-insensitive asthma. We herein review several distinct techniques for the assessment of (1) the cellular response to GCs including the effect of GCs on cell viability, adhesion, and mediator release; (2) the functionality of GC receptors, including phosphorylation of the GR, nuclear translocation, and binding activities; and (3) the characterization of proteins differentially expressed in steroid-resistant cells by comparative 2DE-gel electrophoresis-based techniques and mass spectrometry. These comprehensive approaches are expected to reveal novel candidates for biomarkers of steroid insensitivity, which may lead to the development of effective therapeutic interventions for patients with chronic steroid-resistant asthma. C1 [Pazdrak, Konrad; Kurosky, Alexander] Univ Texas Med Branch, Dept Biochem & Mol Biol, Inst Translat Sci, NHLBI Prote Ctr Airway Inflammat, Galveston, TX 77555 USA. RP Pazdrak, K (reprint author), Univ Texas Med Branch, Dept Biochem & Mol Biol, Inst Translat Sci, NHLBI Prote Ctr Airway Inflammat, 2-230 Basic Sci Bldg,301 Univ Blvd, Galveston, TX 77555 USA. EM kopazdra@utmb.edu; akurosky@utmb.edu FU NCATS NIH HHS [UL1 TR000071] NR 72 TC 1 Z9 1 U1 1 U2 6 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-8603-9; 978-1-4614-8602-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2014 VL 795 BP 255 EP 272 DI 10.1007/978-1-4614-8603-9_16 D2 10.1007/978-1-4614-8603-9 PG 18 WC Allergy; Biology; Medicine, Research & Experimental; Respiratory System SC Allergy; Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Respiratory System GA BA1AR UT WOS:000332364000018 PM 24162914 ER PT S AU Vessel, EA Stahl, J Maurer, N Denker, A Starr, GG AF Vessel, Edward A. Stahl, Jonathan Maurer, Natalia Denker, Alexander Starr, G. Gabrielle BE Rogowitz, BE Pappas, TN DeRidder, H TI Personalized Visual Aesthetics SO HUMAN VISION AND ELECTRONIC IMAGING XIX SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Human Vision and Electronic Imaging XIX CY FEB 03-06, 2014 CL San Francisco, CA SP Soc Imaging Sci & Technol, SPIE, Qualcomm Inc, RIT Sch Media Sci DE Aesthetics; individual differences; visual preference; artwork; landscapes; faces; architecture ID BRAINS DEFAULT NETWORK; FACIAL ATTRACTIVENESS; BEAUTY; BEHOLDER AB How is visual information linked to aesthetic experience, and what factors determine whether an individual finds a particular visual experience pleasing? We have previously shown that individuals' aesthetic responses are not determined by objective image features but are instead a function of internal, subjective factors that are shaped by a viewers' personal experience. Yet for many classes of stimuli, culturally shared semantic associations give rise to similar aesthetic taste across people. In this paper, we investigated factors that govern whether a set of observers will agree in which images are preferred, or will instead exhibit more "personalized" aesthetic preferences. In a series of experiments, observers were asked to make aesthetic judgments for different categories of visual stimuli that are commonly evaluated in an aesthetic manner (faces, natural landscapes, architecture or artwork). By measuring agreement across observers, this method was able to reveal instances of highly individualistic preferences. We found that observers showed high agreement on their preferences for images of faces and landscapes, but much lower agreement for images of artwork and architecture. In addition, we found higher agreement for heterosexual males making judgments of beautiful female faces than of beautiful male faces. These results suggest that preferences for stimulus categories that carry evolutionary significance (landscapes and faces) come to rely on similar information across individuals, whereas preferences for artifacts of human culture such as architecture and artwork, which have fewer basic-level category distinctions and reduced behavioral relevance, rely on a more personalized set of attributes. C1 [Vessel, Edward A.] NYU, Ctr Brain Imaging, 4 Washington Pl,Rm 156, New York, NY 10003 USA. [Stahl, Jonathan; Maurer, Natalia] NYU, Dept Physiol, New York, NY 10003 USA. [Denker, Alexander] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Starr, G. Gabrielle] NYU, Dept English, New York, NY 10003 USA. RP Vessel, EA (reprint author), NYU, Ctr Brain Imaging, 4 Washington Pl,Rm 156, New York, NY 10003 USA. EM ed.vessel@nyu.edu RI Vessel, Edward/C-9580-2013 FU NYU University FX Nava Rubin, Tyra Lindstrom, Lucy Owen, Melanie Wen, Richard Russell, Oriana Neidecker. This work was supported by a grant from the NYU University Research Challenge Fund to G. S. and E. V. NR 17 TC 3 Z9 3 U1 1 U2 6 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9931-8 J9 PROC SPIE PY 2014 VL 9014 AR UNSP 90140S DI 10.1117/12.2043126 PG 8 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BA3LU UT WOS:000334350600021 ER PT J AU Zheng, CY Baum, BJ AF Zheng, Changyu Baum, Bruce J. TI All Human EFI alpha Promoters Are Not Equal: Markedly Affect Gene Expression in Constructs from Different Sources SO INTERNATIONAL JOURNAL OF MEDICAL SCIENCES LA English DT Article DE promoter; EF1 alpha; gene therapy ID CELL-LINE; MEDIATED TRANSFER; SALIVARY-GLANDS; ADENOVIRUS; DELIVERY; DNA; IDENTIFICATION; VECTORS; MICE AB The promoter is a major element in the expression cassette of gene therapy vectors. Optimal promoter selection can enhance target specificity and gene expression. Recently, we evaluated three different human elongation factor 1 alpha (EFI alpha) promoters. The three promoters were put into the same expression vector, pAC-luc, driving expression of the luciferase cDNA. The activity from one EFI alpha promoter (termed EFI alpha-3), obtained in a commercial vector, was markedly lower when tested in vitro (from 50 - 500 x) in four cell lines and in vivo in rat submandibular glands (similar to 250 x). Sequence differences in the EFI alpha -3 promoter likely account for the activity differences seen. Investigators need to recognize that all promoters of the same name may not be equivalent in driving transgene expression. C1 [Zheng, Changyu; Baum, Bruce J.] NIDCR, MPTB, NIH, DHHS, Bethesda, MD 20892 USA. RP Zheng, CY (reprint author), NIDCR, MPTB, NIH, Bldg 10,Room 1A01,MSC 1190,9000 Rockville Pike, Bethesda, MD 20892 USA. EM czheng@mail.nih.gov FU Division of Intramural Research, National Institute of Dental and Craniofacial Research, NIH FX Our research is supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research, NIH. NR 20 TC 1 Z9 1 U1 0 U2 2 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-1907 J9 INT J MED SCI JI Int. J. Med. Sci. PY 2014 VL 11 IS 5 BP 404 EP 408 DI 10.7150/ijms.8033 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AF3JZ UT WOS:000334609600001 PM 24688302 ER PT J AU Schron, E Friedmann, E Thomas, SA AF Schron, Eleanor Friedmann, Erika Thomas, Sue A. TI Does Health-Related Quality of Life Predict Hospitalization or Mortality in Patients with Atrial Fibrillation? SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; hospitalization; medical outcomes study (SF-36); Mortality; quality of life; quality of life index-cardiac version (QLI-CV); survival ID RHYTHM MANAGEMENT AFFIRM; HEART-FAILURE; VENTRICULAR-ARRHYTHMIAS; RANDOMIZED-TRIAL; LONG-TERM; RISK; IMPACT; PREVALENCE; THERAPY; ASSOCIATION AB QOL Predicts Hospitalization and Mortality in AF Background: Poor health-related quality of life (QOL) is related to morbidity and mortality in coronary heart disease and ventricular arrhythmias as well as to mortality in patients with heart failure (HF) and atrial fibrillation (AF). This study examined the contributions of QOL to the prediction of 1-year hospitalization and mortality in patients with AF, independent of HF. Methods: This study used the public use dataset from the NHLBI/NIH AFFIRM randomized clinical trial. Patients enrolled in the QOL substudy (N = 693) were randomly assigned to rate or rhythm control. QOL was assessed with the Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and the Quality of Life Index-Cardiac Version (QLI-CV). Data were analyzed with logistic regression to predict 1-year hospitalization and Cox proportional hazards analysis to predict mortality. Results: In the first year of participation in the study 37% (n = 256) were hospitalized; mortality was 14.3% (n = 93) with mean follow-up of 3.5 years. Patients' mean age was 69.8 +/- 8.2 years, were largely male (62%), and white (93%). Patient histories included 70.8% hypertension, 38.2% coronary artery disease (CAD), and 23.7% HF. History of stroke, HF, rhythm control arm, lower SF-36 mental component scores (MCS), and lower SF-36 physical component scores (PCS) predicted hospitalization (P < 0.001). Diabetes, female gender, older age, CAD, hypertension, and lower PCS predicted mortality (P < 0.001). Conclusion: QOL adds meaningful information beyond traditional biomedical factors to the prediction of mortality and/or hospitalization of patients with AF. Interventions for improving QOL and helping patients adapt to AF treatments may decrease hospitalization and improve survival. C1 [Schron, Eleanor] NEI, Div Extramural Res, NIH, Bethesda, MD 20892 USA. [Friedmann, Erika; Thomas, Sue A.] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. RP Schron, E (reprint author), NEI, Vis Res Program, Div Extramural Res, NIH, Suite 1300,5635 Fishers Lane,MSC 9300, Bethesda, MD 20892 USA. EM schrone@nei.nih.gov OI Friedmann, Erika/0000-0003-2924-0449 FU NHLBI; AFFIRM Investigators FX The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) is conducted and supported by the NHLBI in collaboration with the AFFIRM Investigators. This manuscript was prepared using a limited access dataset obtained by the NHLBI and does not necessarily reflect the opinions or views of the AFFIRM Study or the NHLBI. NR 55 TC 7 Z9 8 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JAN PY 2014 VL 25 IS 1 BP 23 EP 28 DI 10.1111/jce.12266 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AF2BE UT WOS:000334516800016 PM 24102986 ER PT S AU Le Grice, SFJ Nowotny, M AF Le Grice, Stuart F. J. Nowotny, Marcin BE Murakami, KS Trakselis, MA TI Reverse Transcriptases SO NUCLEIC ACID POLYMERASES SE Nucleic Acids and Molecular Biology LA English DT Article; Book Chapter DE Human immunodeficiency virus; Reverse transcription; DNA polymerase; Ribonuclease H; Antiviral therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; RNASE-H DOMAIN; STRAND DISPLACEMENT SYNTHESIS; TERMINAL REPEAT RETROTRANSPOSON; DEPENDENT DNA POLYMERASE; ACTIVE-SITE ASPARTATE; COLI RIBONUCLEASE HI; ROUS-SARCOMA-VIRUS; ESCHERICHIA-COLI AB Reverse transcriptases (RTs) catalyze the multi-step process that converts the single-stranded viral RNA genome to double-stranded integration-competent DNA, a process that is essential for the proliferation of retroviruses and retrotransposons. The former are released from cells as infectious particles and include human immunodeficiency virus (HIV) and hepadnaviruses such as hepatitis B virus (HBV). In contrast, retrotransposons are restricted to intracellular proliferation cycle and are very common in eukaryotic genomes. The N-terminal DNA polymerase domain of RTs structurally resembles other nucleic acid polymerases and assumes the topology of a right hand, with subdomains designated fingers, palm, and thumb. RTs exhibit low fidelity and processivity and are capable of both intra-and intermolecular strand displacement synthesis. A distinguishing feature of RTs is the presence of a C-terminal ribonuclease H (RNase H) domain in enzymes from viruses and long terminal repeat (LTR)-containing retrotransposons. The general role of this domain is sequence-independent removal of RNA from the RNA/DNA hybrid intermediates of reverse transcription, although precise cleavage is also required to mediate key steps such as (+) strand primer selection and DNA strand transfer. In LTR retroelements the RNase H domain is located immediately following the thumb subdomain, while in retroviruses an RNase H-like "connection domain" devoid of catalytic activity is followed by the catalytically competent C-terminal RNase H domain. DNA polymerase and RNase H activities are coordinated, but RNA/DNA hybrid hydrolysis is significantly slower than nucleotide incorporation. Whether this reflects simultaneous or individual active site occupancy of the nucleic acid substrate remains controversial. C1 [Le Grice, Stuart F. J.] Frederick Natl Lab Canc Res, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Nowotny, Marcin] Int Inst Mol & Cell Biol, Lab Prot Struct, PL-02109 Warsaw, Poland. RP Le Grice, SFJ (reprint author), Frederick Natl Lab Canc Res, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. EM legrices@mail.nih.gov; mnowotny@iimcb.gov.pl NR 149 TC 3 Z9 3 U1 1 U2 8 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0933-1891 BN 978-3-642-39796-7; 978-3-642-39795-0 J9 NUCLEIC ACIDS MOL BI JI Nucleic Acids Molec. Biol. PY 2014 VL 30 BP 189 EP 214 DI 10.1007/978-3-642-39796-7_8 D2 10.1007/978-3-642-39796-7 PG 26 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BA0WN UT WOS:000332326100009 ER PT J AU Aprahamian, I de Sousa, RT Valiengo, LDL Machado-Vieira, R Forlenza, OV AF Aprahamian, Ivan de Sousa, Rafael Teixeira Lane Valiengo, Leandro da Costa Machado-Vieira, Rodrigo Forlenza, Orestes Vicente TI Lithium safety and tolerability in mood disorders: a critical review SO REVISTA DE PSIQUIATRIA CLINICA LA English DT Review DE Lithium; mood disorders; safety; tolerability ID LONG-TERM LITHIUM; NONCONVULSIVE STATUS EPILEPTICUS; GLOMERULAR-FILTRATION-RATE; BODY-WEIGHT REGULATION; OF-THE-LITERATURE; BIPOLAR DISORDER; DOUBLE-BLIND; MAINTENANCE TREATMENT; PARATHYROID FUNCTION; DIABETES-INSIPIDUS AB Background: Lithium is a first-line treatment for bipolar disorder in all phases, also indicated as add-on drug for unipolar depression and suicide prevention. This study encompasses a broad critical review on the safety and tolerability of lithium for mood disorders. Methods: A computerized search for English written human studies was made in MEDLINE, using the keywords "lithium" and "mood disorders", starting from July 1993 through July 2013 (n = 416). This initial search aimed to select clinical trials, prospective data, and controlled design studies of lithium treatment for mood disorders reporting adverse effects (n = 36). The final selection yielded 91 studies. Results: The most common general side effects in patients on lithium treatment were thirst, frequent urination, dry mouth, weight gain, fatigue and cognitive complaints. Lithium users showed a high prevalence of hypothyroidism, hyperparathyroidism, and decrease in urinary concentration ability. Reduction of glomerular filtration rate in patients using lithium was also observed, but in a lesser extent. The evidence of teratogenicity associated with lithium use is not well established. Anti-inflammatory non-steroidal drugs, thiazide diuretics, angiotensin-converting enzyme inhibitors, and alprazolam may increase serum lithium and the consequent risk for intoxication. Discussion: Short-term lithium treatment is associated with mild side effects. Medium and long-term lithium treatment, however, might have effects on target organs which may be prevented by periodical monitoring. Overall, lithium is still a safe option for the treatment of mood disorders. C1 [Aprahamian, Ivan; de Sousa, Rafael Teixeira; Lane Valiengo, Leandro da Costa; Machado-Vieira, Rodrigo; Forlenza, Orestes Vicente] Univ Sao Paulo, Fac Med, Dept & Inst Psychiat, Lab Neurosci LIM 27, BR-05403010 Sao Paulo, Brazil. [Lane Valiengo, Leandro da Costa] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. RP Aprahamian, I (reprint author), Univ Sao Paulo, Fac Med, Dept & Inst Psychiat, Lab Neurosci LIM 27, Rua Dr Ovidio Pires de Campos 785, BR-05403010 Sao Paulo, Brazil. EM aprahamian@usp.br RI Forlenza, Orestes/B-8848-2013; Aprahamian, Ivan/G-8905-2013; MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 NR 92 TC 3 Z9 3 U1 3 U2 17 PU UNIV SAO PAULO, INST PSIQUIATRIA PI SAO PAULO PA RUA OVIDIO PIRES CAMPOS, 785, 1 ANDAR, SAO PAULO, 05403-010, BRAZIL SN 0101-6083 J9 REV PSIQ CLIN-BRAZIL JI Rev. Psiquiatr. Clin. PY 2014 VL 41 IS 1 BP 9 EP 14 DI 10.1590/0101-60830000411914 PG 6 WC Psychiatry SC Psychiatry GA AF3GI UT WOS:000334599200003 ER PT J AU Duverger, O Morasso, MI AF Duverger, Olivier Morasso, Maria I. TI To grow or not to grow: Hair morphogenesis and human genetic hair disorders SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE Hair follicle; Morphogenesis; Shaft differentiation; Genetic disorders; Alopecia ID HYPOHIDROTIC ECTODERMAL DYSPLASIA; PROTEIN-COUPLED RECEPTOR; OF-FUNCTION MUTATIONS; SYNDROME TYPE-I; HYPOTRICHOSIS SIMPLEX; MENKES DISEASE; CANDIDATE GENE; WOOLLY HAIR; DNA-REPAIR; FOLLICLE DIFFERENTIATION AB Mouse models have greatly helped in elucidating the molecular mechanisms involved in hair formation and regeneration. Recent publications have reviewed the genes involved in mouse hair development based on the phenotype of transgenic, knockout and mutant animal models. While much of this information has been instrumental in determining molecular aspects of human hair development and cycling, mice exhibit a specific pattern of hair morphogenesis and hair distribution throughout the body that cannot be directly correlated to human hair. In this mini-review, we discuss specific aspects of human hair follicle development and present an up-to-date summary of human genetic disorders associated with abnormalities in hair follicle morphogenesis, structure or regeneration. Published by Elsevier Ltd. C1 [Duverger, Olivier; Morasso, Maria I.] NIAMSD, Skin Biol Lab, Bethesda, MD 20892 USA. RP Duverger, O (reprint author), NIAMSD, Skin Biol Lab, Bethesda, MD 20892 USA. EM duvergero@mail.nih.gov; morasso@nih.gov FU Intramural Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health FX The authors thank Ms. Julie Erthal and Ms. Meghan Kellett for comments on the manuscript. We also thank Dr. Karen Holbrook for providing human hair follicle images. This work is supported by funding by the Intramural Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health. NR 85 TC 6 Z9 6 U1 2 U2 20 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD JAN-FEB PY 2014 VL 25 BP 22 EP 33 DI 10.1016/j.semcdb.2013.12.006 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA AE9FH UT WOS:000334310500004 PM 24361867 ER PT J AU Patel, VN Hoffman, MP AF Patel, Vaishali N. Hoffman, Matthew P. TI Salivary gland development: A template for regeneration SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE Salivary gland development; Submandibular gland; Branching morphogenesis; Stem cells; Progenitor cells; Regeneration; Parasympathetic innervation ID EMBRYONIC SUBMANDIBULAR-GLAND; EPITHELIAL-CELL DYNAMICS; BRANCHING MORPHOGENESIS; PROGENITOR CELLS; STEM-CELLS; E-CADHERIN; PANCREATIC LINEAGES; LUMEN FORMATION; IN-VIVO; TRANSPLANTATION AB The mammalian salivary gland develops as a highly branched structure designed to produce and secrete saliva. This review will focus on research on mouse submandibular gland development and the translation of this basic research toward therapy for patients suffering from salivary hypofunction. Here we review the most recent literature that has enabled a better understanding of the mechanisms of salivary gland development. Additionally, we discuss approaches proposed to restore salivary function using gene and cell-based therapy. Increasing our understanding of the developmental mechanisms involved during development is critical to design effective therapies for regeneration and repair of damaged glands. Published by Elsevier Ltd. C1 [Patel, Vaishali N.; Hoffman, Matthew P.] NIDCR, Matrix & Morphogenesis Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Hoffman, MP (reprint author), NIDCR, Matrix & Morphogenesis Sect, LCDB, NIH, Bldg 30,Room 433,30 Convent Dr MSC 4370, Bethesda, MD 20892 USA. EM mhoffman@mail.nih.gov FU Intramural Research Program of the NIDCR at the NIH FX The authors would like to thank Drs. Joao Ferreira, Isabelle Lombaert and Wendy Knosp for critical reading of this manuscript. This work was supported by the Intramural Research Program of the NIDCR at the NIH. NR 83 TC 22 Z9 22 U1 0 U2 13 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD JAN-FEB PY 2014 VL 25 BP 52 EP 60 DI 10.1016/j.semcdb.2013.12.001 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA AE9FH UT WOS:000334310500007 PM 24333774 ER PT J AU Rong, PF Yang, K Srivastan, A Kiesewetter, DO Yue, XY Wang, F Nie, LM Bhirde, A Wang, Z Liu, Z Niu, G Wang, W Chen, XY AF Rong, Pengfei Yang, Kai Srivastan, Avinash Kiesewetter, Dale O. Yue, Xuyi Wang, Fu Nie, Liming Bhirde, Ashwinkumar Wang, Zhe Liu, Zhuang Niu, Gang Wang, Wei Chen, Xiaoyuan TI Photosensitizer Loaded Nano-Graphene for Multimodality Imaging Guided Tumor Photodynamic Therapy SO THERANOSTICS LA English DT Article DE Graphene oxide; HPPH; photodynamic therapy; positron emission tomography; optical imaging ID IN-VIVO; PHOTOTHERMAL THERAPY; DRUG-DELIVERY; PHTHALOCYANINE TETRASULFONATE; BIOMEDICAL APPLICATIONS; CANCER; OXIDE; EFFICACY; MICE; HPPH AB Graphene, a 2-dimensional carbon nanomaterial, has attracted wide attention in biomedical applications, owing to its intrinsic physical and chemical properties. In this work, a photosensitizer molecule, 2-(I-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha (HPPH or Photochlor (R)), is loaded onto polyethylene glycol (PEG)-functionalized graphene oxide (GO) via supramolecular Pi-Pi stacking. The obtained GO-PEG-HPPH complex shows high HPPH loading efficiency. The in vivo distribution and delivery were tracked by fluorescence imaging as well as positron emission tomography (PET) after radiolabeling of HPPH with Cu-64. Compared with free HPPH, GO-PEG-HPPH offers dramatically improved photodynamic cancer cell killing efficacy due to the increased tumor delivery of HPPH. Our study identifies a role for graphene as a carrier of PDT agents to improve PDT efficacy and increase long-term survival following treatment. C1 [Rong, Pengfei; Wang, Wei] Cent S Univ, Xiangya Hosp 3, Dept Radiol, Changsha 410013, Hunan, Peoples R China. [Rong, Pengfei; Yang, Kai; Srivastan, Avinash; Kiesewetter, Dale O.; Yue, Xuyi; Wang, Fu; Nie, Liming; Bhirde, Ashwinkumar; Wang, Zhe; Niu, Gang; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. Cent S Univ, State Key Lab Powder Met, Changsha 410013, Hunan, Peoples R China. [Yang, Kai] Soochow Univ, Inst Funct Nano & Soft Mat FUNSOM, Suzhou 215123, Jiangsu, Peoples R China. [Yue, Xuyi] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361102, Fujian, Peoples R China. RP Niu, G (reprint author), Cent S Univ, Xiangya Hosp 3, Dept Radiol, Changsha 410013, Hunan, Peoples R China. EM niug@mail.nih.gov; cjr.wangwei@vip.163.com; shawn.chen@nih.gov RI Nie, Liming/F-7718-2016; OI Wang, Fu/0000-0001-9222-0833 FU Major State Basic Research Development Program of China [2013CB733802, 2014CB744503]; National Science Foundation of China (NSFC) [81301257, 81301256, 81371596]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), NCI); National Institutes of Health (NIH) FX This work was supported by the Major State Basic Research Development Program of China (973 Program) (2013CB733802, 2014CB744503), National Science Foundation of China (NSFC) (81301257, 81301256, 81371596), and the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), NCI), National Institutes of Health (NIH). NR 45 TC 58 Z9 58 U1 24 U2 143 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2014 VL 4 IS 3 BP 229 EP 239 DI 10.7150/thno.8070 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AF4EJ UT WOS:000334663900001 PM 24505232 ER PT J AU Wan, ZH Mao, HJ Guo, M Li, YL Zhu, AJ Yang, H He, H Shen, JK Zhou, LJ Jiang, Z Ge, CC Chen, XY Yang, XL Liu, G Chen, HB AF Wan, Zhihui Mao, Huajian Guo, Miao Li, Yanli Zhu, Aijun Yang, Hong He, Hui Shen, Junkang Zhou, Lijuan Jiang, Zhen Ge, Cuicui Chen, Xiaoyuan Yang, Xiangliang Liu, Gang Chen, Huabing TI Highly Efficient Hierarchical Micelles Integrating Photothermal Therapy and Singlet Oxygen-Synergized Chemotherapy for Cancer Eradication SO THERANOSTICS LA English DT Article DE Hierarchical micelles; Photothermal therapy; Singlet oxygen; Synergistic therapy; Cancer eradication ID RESPONSIVE GOLD NANOPARTICLES; INDOCYANINE-GREEN; PHOTODYNAMIC THERAPY; SILICA NANOPARTICLES; COMBINATION THERAPY; THERANOSTIC AGENT; INFRARED LIGHT; CELLS; PHOTOSENSITIZER; DOXORUBICIN AB It is highly desirable to develop theranostic nanoparticles for achieving cancer imaging with enhanced contrast and simultaneously multimodal synergistic therapy. Herein, we report a theranostic micelle system hierarchically assembling cyanine dye (indocyanine green) and chemotherapeutic compound (doxorubicin) (I/D-Micelles) as a novel theranostic platform with high drug loading, good stability and enhanced cellular uptake via clathrin-mediated endocytosis. I/D-Micelles exhibit the multiple functionalities including near-infrared fluorescence (NIRF), hyperthermia and intracellular singlet oxygen from indocyanine green, and simultaneous cytotoxicity from doxorubicin. Upon photoirradiation, I/D-Micelles can induce NIRF imaging, acute photothermal therapy via hyperthermia and simultaneous synergistic chemotherapy via singlet oxygen- triggered disruption of lysosomal membranes, eventually leading to enhanced NIRF imaging and superior tumor eradication without any re-growth. Our results suggest that the hierarchical micelles can act as a superior theranostic platform for cancer imaging and multimodal synergistic therapy. C1 [Wan, Zhihui; Mao, Huajian; Guo, Miao; Li, Yanli; Zhu, Aijun; Yang, Hong; He, Hui; Chen, Huabing] Soochow Univ, Jiangsu Key Lab Translat Res & Therapy Neuropsyco, Suzhou 215123, Peoples R China. [Wan, Zhihui; Mao, Huajian; Guo, Miao; Li, Yanli; Zhu, Aijun; Yang, Hong; He, Hui; Chen, Huabing] Soochow Univ, Coll Pharmaceut Sci, Suzhou 215123, Peoples R China. [Shen, Junkang; Zhou, Lijuan; Jiang, Zhen] Soochow Univ, Affiliated Hosp 2, Dept Radiol, Suzhou 215004, Peoples R China. [Ge, Cuicui] Soochow Univ, Sch Radiol & Interdisciplinary Sci RAD X, Suzhou 215123, Peoples R China. [Ge, Cuicui] Soochow Univ, Sch Radiat Med & Protect, Suzhou 215123, Peoples R China. [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Yang, Xiangliang] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430074, Peoples R China. [Liu, Gang] Xiamen Univ, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China. [Liu, Gang] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361102, Peoples R China. RP Chen, HB (reprint author), Soochow Univ, Jiangsu Key Lab Translat Res & Therapy Neuropsyco, Suzhou 215123, Peoples R China. EM chenhb@suda.edu.cn RI Chen, Huabing/B-3687-2011 FU National Natural Science Foundation of China [81202472, 51273165]; National Basic Research Program [2012CB932500, 2013CB733802]; priority academic program development of Jiangsu higher education institutions (PAPD) FX This work was supported by National Natural Science Foundation of China (81202472, 51273165), National Basic Research Program (2012CB932500, 2013CB733802), and the priority academic program development of Jiangsu higher education institutions (PAPD). NR 47 TC 36 Z9 37 U1 11 U2 101 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2014 VL 4 IS 4 BP 399 EP 411 DI 10.7150/thno.8171 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AF4ES UT WOS:000334664800003 PM 24578723 ER PT J AU Wu, CX Yue, XY Lang, LX Kiesewetter, DO Li, F Zhu, ZH Niu, G Chen, XY AF Wu, Chenxi Yue, Xuyi Lang, Lixin Kiesewetter, Dale O. Li, Fang Zhu, Zhaohui Niu, Gang Chen, Xiaoyuan TI Longitudinal PET Imaging of Muscular Inflammation Using F-18-DPA-714 and F-18-Alfatide II and Differentiation with Tumors SO THERANOSTICS LA English DT Article DE F-18-DPA-714; F-18-Alfatide II; positron emission tomography; inflammation; tumor; TSPO ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; RHEUMATOID-ARTHRITIS; NERVOUS-SYSTEM; BRAIN-INJURY; MACROPHAGES; MODEL; DISEASE; CANCER; MICE AB Aim: F-18-DPA-714 is a PET tracer that recognizes macrophage translocator protein (TSPO), and F-18-Alfatide II (F-18-AlF-NOTA-E[PEG(4)-c(RGDfk)](2)) is specific for integrin alpha(v)beta(3). This study aims to apply these two tracers for longitudinal PET imaging of muscular inflammation, and evaluate the value of F-18-DPA-714 in differentiating inflammation from tumor. Methods: RAW264.7 mouse macrophage cells were used for cell uptake analysis of F-18-DPA-714. A mouse hind limb muscular inflammation model was established by intramuscular injection of turpentine oil. For the inflammation model, PET imaging was performed at different days using F-18-DPA-714 and F-18-Alfatide II. The specificity of the imaging probes was tested by co-or pre-injection of PK11195 or unlabeled RGD (Arg-Gly-Asp) peptide. PET imaging using F-18-DPA-714 was performed in A549, HT29, U87MG, INS-1, and 4TI xenograft models. Immunofluorescence staining was performed to evaluate infiltrated macrophages and angiogenesis in inflammation and/ or tumors. Results: Uptake of F-18-DPA-714 in RAW264.7 cells was 45.5% at 1 h after incubation, and could be blocked by PK11195. PET imaging showed increased F-18-DPA-714 and F-18-Alfatide II uptake at inflammatory muscles. Peak uptake of F-18-DPA-714 was seen on day 6 (4.02 +/- 0.64 % ID/ g), and peak uptake of F-18-Alfatide II was shown on day 12 (1.87 +/- 0.35 % ID/ g) at 1 h p. i.. Tracer uptakes could be inhibited by PK11195 for F-18-DPA-714 or cold RGD for F-18-Alfatide II. Moreover, macrophage depletion with liposomal clodronate also reduced the local accumulation of both tracers. A549, HT29, U87MG, INS-1, and 4TI tumor uptakes of F-18-DPA-714 (0.46 +/- 0.28, 0.91 +/- 0.08, 1.69 +/- 0.67, 1.13 +/- 0.33, 1.22 +/- 0.55 % ID/ g at 1 h p. i., respectively) were significantly lower than inflammation uptake (All P < 0.05). Conclusion: PET imaging using F-18-DPA-714 as a TSPO targeting tracer could evaluate the dynamics of macrophage activation and infiltration in different stages of inflammatory diseases. The concomitant longitudinal PET imaging with both F-18-DPA-714 and F-18-Alfatide II matched the causal relationship between macrophage infiltration and angiogenesis. Moreover, we found F-18-DPA-714 uptake in several types of tumors is significantly lower than that in inflammatory muscles, suggesting F-18-DPA-714 PET has the potential for better differentiation of tumor and non-tumor inflammation. C1 [Wu, Chenxi; Li, Fang; Zhu, Zhaohui] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Nucl Med, Beijing 100730, Peoples R China. [Wu, Chenxi; Li, Fang; Zhu, Zhaohui] Peking Union Med Coll CAMS & PUMC, Beijing 100730, Peoples R China. [Wu, Chenxi; Yue, Xuyi; Lang, Lixin; Kiesewetter, Dale O.; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. RP Zhu, ZH (reprint author), Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Nucl Med, 1 Shuaifuyuan,Wangfujing St, Beijing 100730, Peoples R China. EM zhuzhh@pumch.cn; shawn.chen@nih.gov FU Department of Nuclear Medicine, Peking Union Medical College Hospital (PUMCH); National Institute of Biomedical Imaging and Bioengineering (NIBIB); National Institutes of Health (NIH) FX This work was supported by Department of Nuclear Medicine, Peking Union Medical College Hospital (PUMCH), and the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 40 TC 13 Z9 13 U1 0 U2 6 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2014 VL 4 IS 5 BP 546 EP 555 DI 10.7150/thno.8159 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AF4EX UT WOS:000334665300007 PM 24672585 ER PT J AU Bae, KT Sun, HL Lee, JG Bae, K Wang, JH Tao, C Chapman, AB Torres, VE Grantham, JJ Mrug, M Bennett, WM Flessner, MF Landsittel, DP AF Bae, Kyongtae T. Sun, Hongliang Lee, June Goo Bae, Kyungsoo Wang, Jinhong Tao, Cheng Chapman, Arlene B. Torres, Vicente E. Grantham, Jared J. Mrug, Michal Bennett, William M. Flessner, Michael F. Landsittel, Doug P. CA Consortium Radiologic Imaging Stud TI Novel Methodology to Evaluate Renal Cysts in Polycystic Kidney Disease SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Kidney; Polycystic kidney diseases; Renal cysts; Magnetic resonance imaging; Segmentation ID VOLUME; SEGMENTATION; CONSORTIUM; GROWTH; IMAGES; COHORT; ADPKD; MRI AB Aim: To develop and assess a semiautomated method for segmenting and counting individual renal cysts from midslice MR images in patients with autosomal dominant polycystic kidney disease (ADPKD). Methods: A semiautomated method was developed to segment and count individual renal cysts from mid-slice MR images in 241 subjects with ADPKD from the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease. For each subject, a mid-slice MR image was selected from each set of corona! T2-weighted MR images covering the entire kidney. The selected midslice image was processed with the semiautomated method to segment and count individual renal cysts. The number of cysts from the mid-slice image of each kidney was also measured by manual counting. The level of agreement between the semiautonnated and manual cyst counts was compared using intraclass correlation (ICC) and a Bland-Altman plot. Results: Individual renal cysts were successfully segmented using the semiautomated method in all 241 cases. The number of cysts in each kidney measured with the semiautomated and manual counting methods correlated well (ICC= 0.96 for the right or left kidney), with a small average difference (-0.52, with higher semiautomated counts, for the right kidney, and 0.13, with higher manual counts, for the left kidney) in the senniautomated method. However, there was substantial variation in a small number of subjects; 6 of 241 participants (2.5%) had a difference in the total cyst count of more than 15. Conclusion: We have developed a semiautomated method to segment individual renal cysts from mid-slice MR images in ADPKD kidneys as a quantitative indicator of characterization and disease progression of ADPKD. (C) 2014 S. Karger AG, Basel C1 [Bae, Kyongtae T.; Sun, Hongliang; Lee, June Goo; Wang, Jinhong; Tao, Cheng] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA 15213 USA. [Landsittel, Doug P.] Univ Pittsburgh, Sch Med, Dept Internal Med, Pittsburgh, PA 15213 USA. [Chapman, Arlene B.] Emory Univ, Sch Med, Dept Internal Med, Atlanta, GA USA. [Torres, Vicente E.] Mayo Coll Med, Dept Internal Med, Rochester, MN USA. [Grantham, Jared J.] Univ Kansas, Med Ctr, Dept Internal Med, Kansas City, KS 66103 USA. [Mrug, Michal] Univ Alabama Birmingham, Div Nephrol, Birmingham, AL USA. [Bennett, William M.] Legacy Good Samaritan Hosp, Portland, OR USA. [Flessner, Michael F.] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA. [Bae, Kyungsoo] Gyeongsang Natl Univ, Sch Med, Dept Radiol, Jinju, South Korea. RP Bae, KT (reprint author), Univ Pittsburgh, Sch Med, Dept Radiol, Presbyterian South Tower,Room 3950,200 Lothrop St, Pittsburgh, PA 15213 USA. EM baek@upmc.edu FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [DK056943, DK056956, DK056957, DK056961]; National Center for Research Resources General Clinical Research Centers [RR000039, RR00585, RR23940, RR000032]; National Center for Research Resources [RR025008, RR024150, RR033179, RR025777, UL1TR000165, RR024153, UL1TR000005] FX The CRISP study is supported by cooperative agreements from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (DK056943, DK056956, DK056957, DK056961) and by the National Center for Research Resources General Clinical Research Centers at each institution (RR000039, Emory University; RR00585, Mayo College of Medicine; RR23940, Kansas University Medical Center; RR000032, University of Alabama at Birmingham) and the National Center for Research Resources Clinical and Translational Science Awards at each institution (RR025008, Emory University; RR024150, Mayo College of Medicine; RR033179, Kansas University Medical Center; RR025777 and UL1TR000165, University of Alabama at Birmingham; RR024153 and UL1TR000005, University of Pittsburgh School of Medicine). The investigators are indebted to the radiologists, radiology technologists, imaging engineering and study coordinators in CRISP. NR 20 TC 1 Z9 1 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2014 VL 39 IS 3 BP 210 EP 217 DI 10.1159/000358604 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AE7DK UT WOS:000334156700004 PM 24576800 ER PT J AU Seifter, A Singh, S McArdle, PF Ryan, KA Shuldiner, AR Mitchell, BD Schaffer, AA AF Seifter, Ari Singh, Sarabdeep McArdle, Patrick F. Ryan, Kathleen A. Shuldiner, Alan R. Mitchell, Braxton D. Schaeffer, Alejandro A. TI Analysis of the bereavement effect after the death of a spouse in the Amish: a population-based retrospective cohort study SO BMJ OPEN LA English DT Article DE Epidemiology; Geriatric Medicine; Mental Health; Public Health ID SEX-DIFFERENCES; SOCIAL SUPPORT; CONJUGAL BEREAVEMENT; MARITAL-STATUS; MORTALITY; WIDOWHOOD; RISK AB Objective This study investigates the association between bereavement and the mortality of a surviving spouse among Amish couples. We hypothesised that the bereavement effect would be relatively small in the Amish due to the unusually cohesive social structure of the Amish that might attenuate the loss of spousal support. Design Population-based cohort study. Setting The USA. Participants 10892 Amish couples born during 1725-1900 located in Pennsylvania, Ohio and Indiana. All the participants are deceased. Outcome measures The survival time is age'; event is death'. Hazard ratios (HRs) of widowed individuals with respect to gender, age at widowhood, remarriage, the number of surviving children and time since bereavement. Results We observed HRs for widowhood ranging from 1.06 to 1.26 over the study period (nearly all differences significant at p<0.05). Mortality risks tended to be higher in men than in women and in younger compared with older bereaved spouses. There were significantly increased mortality risks in widows and widowers who did not remarry. We observed a higher number of surviving children to be associated with increased mortality in men and women. Mortality risk following bereavement was higher in the first 6months among men and women. Conclusions We conclude that bereavement effects remain apparent even in this socially cohesive Amish community. Remarriage is associated with a significant decrease in the mortality risk among Amish individuals. Contrary to results from previous studies, an increase in the number of surviving children was associated with decreased survival rate. C1 [Seifter, Ari; McArdle, Patrick F.; Ryan, Kathleen A.; Shuldiner, Alan R.; Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Seifter, Ari; McArdle, Patrick F.; Ryan, Kathleen A.; Shuldiner, Alan R.; Mitchell, Braxton D.] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA. [Singh, Sarabdeep; Schaeffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, DHHS, Bethesda, MD 20892 USA. [Shuldiner, Alan R.; Mitchell, Braxton D.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA. RP Schaffer, AA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, DHHS, Bldg 10, Bethesda, MD 20892 USA. EM schaffer@helix.nih.gov RI Singh, Sarabdeep/D-7881-2017; OI Mitchell, Braxton/0000-0003-4920-4744 FU National Institutes of Health [R01 HL69313, R01 DK54261, R01 AG1872801, R01 HL088119, R01 AR046838, U01 HL72515]; Intramural Research Programme of the National Institutes of Health, NLM; Geriatric Research and Education Center, Baltimore Veterans Administration Medical Center FX This work was supported by research grants R01 HL69313, R01 DK54261, R01 AG1872801, R01 HL088119, R01 AR046838 and U01 HL72515 from the National Institutes of Health. This research was supported in part by the Intramural Research Programme of the National Institutes of Health, NLM and the Geriatric Research and Education Center, Baltimore Veterans Administration Medical Center. NR 26 TC 1 Z9 1 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2014 VL 4 IS 1 DI 10.1136/bmjopen-2013-003670 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AE9FN UT WOS:000334311200013 ER PT J AU Liu, CK Leng, X Hsu, FC Kritchevsky, SB Ding, J Earnest, CP Ferrucci, L Goodpaster, BH Guralnik, JM Lenchik, L Pahor, M Fielding, RA AF Liu, C. K. Leng, X. Hsu, F. -C. Kritchevsky, S. B. Ding, J. Earnest, C. P. Ferrucci, L. Goodpaster, B. H. Guralnik, J. M. Lenchik, L. Pahor, M. Fielding, R. A. TI THE IMPACT OF SARCOPENIA ON A PHYSICAL ACTIVITY INTERVENTION: THE LIFESTYLE INTERVENTIONS AND INDEPENDENCE FOR ELDERS PILOT STUDY (LIFE-P) SO JOURNAL OF NUTRITION HEALTH & AGING LA English DT Article DE Sarcopenia; physical activity; gait speed; short physical performance battery ID RANDOMIZED CONTROLLED-TRIAL; LOWER-EXTREMITY FUNCTION; HOME-BASED EXERCISE; OLDER-ADULTS; MOBILITY LIMITATION; AEROBIC EXERCISE; BODY-COMPOSITION; PERFORMANCE; DISABILITY; HEALTH AB Objective: to determine if Sarcopenia modulates the response to a physical activity intervention in functionally limited older adults. Design: secondary analysis of a randomized controlled trial. Setting: three academic centers. Participants: elders aged 70 to 89 years at risk for mobility disability who underwent dual-energy x-ray absorptiometry (DXA) for body composition at enrollment and follow-up at twelve months (N = 177). Intervention: subjects participated in a physical activity program (PA) featuring aerobic, strength, balance, and flexibility training, or a successful aging (sa) educational program about healthy aging. Measurements: Sarcopenia as determined by measuring appendicular lean mass and adjusting for height and total body fat mass (residuals method), short Physical Performance Battery score (SPPB), and gait speed determined on 400 meter course. Results: at twelve months, Sarcopenic and non-sarcopenic subjects in PA tended to have higher mean SPPB scores (8.7 +/- 0.5 and 8.7 +/- 0.2 points) compared to sarcopenic and non-sarcopenic subjects in sa (8.3 +/- 0.5 and 8.4 +/- 0.2 points, p = 0.24 and 0.10), although the differences were not statistically significant. at twelve months, faster mean gait speeds were observed in PA: 0.93 +/- 0.4 and 0.95 +/- 0.03 meters/second in sarcopenic and non-sarcopenic PA subjects, and 0.89 +/- 0.4 and 0.91 +/- 0.03 meters/second in sarcopenic and non-sarcopenic sa subjects (p = 0.98 and 0.26), although not statistically significant. there was no difference between the sarcopenic and non-sarcopenic groups in intervention adherence or number of adverse events. Conclusion: these data suggest that older adults with sarcopenia, who represent a vulnerable segment of the elder population, are capable of improvements in physical performance after a physical activity intervention. C1 [Liu, C. K.] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer USDA, Boston, MA 02111 USA. [Liu, C. K.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Leng, X.; Hsu, F. -C.; Kritchevsky, S. B.; Ding, J.; Lenchik, L.; Fielding, R. A.] Wake Forest Sch Med, Winston Salem, NC USA. [Earnest, C. P.] Univ Bath, Bath BA2 7AY, Somerset, England. [Ferrucci, L.; Guralnik, J. M.] NIA, Bethesda, MD 20892 USA. [Goodpaster, B. H.] Univ Pittsburgh, Pittsburgh, PA USA. [Guralnik, J. M.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Pahor, M.] Univ Florida, Gainesville, FL USA. RP Liu, CK (reprint author), Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer USDA, 711 Washington St, Boston, MA 02111 USA. EM chliu@bu.edu; roger.Fielding@tufts.edu FU National Institutes of Health/National Institute of aging [U01AG22376]; Intramural Research Program, National Institute for Aging, and National Institutes of Health; Wake Forest Claude D. Pepper older Americans independence Center [1P30AG21332]; U.S. Department of Agriculture [58-1950-0-014]; Boston Claude D. Pepper Older Americans Independence Center [1P30AG031679]; Health resources and Services Administration [D01HP08796]; American Federation for Aging Research; John A. Hartford Foundation through the Center of Excellence in Geriatric Medicine Training Program FX the LiFe-P study was supported by the National Institutes of Health/National Institute of aging Cooperative agreement (U01AG22376) and sponsored in part by the Intramural Research Program, National Institute for Aging, and National Institutes of Health. DXA imaging was supported by the Wake Forest Claude D. Pepper older Americans independence Center (1P30AG21332). Dr. Fielding was supported by the U.S. Department of Agriculture, agreement no. 58-1950-0-014 and by the Boston Claude D. Pepper Older Americans Independence Center (1P30AG031679). Dr. Liu was supported by the Health resources and Services Administration (D01HP08796), the American Federation for Aging Research, and the John A. Hartford Foundation through the Center of Excellence in Geriatric Medicine Training Program. this work was presented at the 2011 annual Meeting of the American geriatrics society in national Harbor, Maryland. NR 28 TC 14 Z9 15 U1 1 U2 10 PU SPRINGER FRANCE PI PARIS PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE SN 1279-7707 EI 1760-4788 J9 J NUTR HEALTH AGING JI J. Nutr. Health Aging PD JAN PY 2014 VL 18 IS 1 BP 59 EP 64 PG 6 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA AF0JU UT WOS:000334400900011 PM 24402391 ER PT J AU Gomez, H Rojas, R Patel, D Tabak, LA Lluch, JM Masgrau, L AF Gomez, Hansel Rojas, Raul Patel, Divya Tabak, Lawrence A. Lluch, Jose M. Masgrau, Laura TI A computational and experimental study of O-glycosylation. Catalysis by human UDP-GalNAc polypeptide: GalNAc transferase-T2 SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID ACETYL-D-GALACTOSAMINE; GAUSSIAN-BASIS SETS; N-ACETYLGALACTOSAMINYLTRANSFERASE; RETAINING GLYCOSYLTRANSFERASE; CONFORMATIONAL-CHANGES; MOLECULAR-DYNAMICS; SUCRASE-ISOMALTASE; CORRELATION-ENERGY; COMPLEX MATERIALS; ZEOLITE STRUCTURE AB It is estimated that >50% of proteins are glycosylated with sugar tags that can modulate protein activity through what has been called the sugar code. Here we present the first QM/MM calculations of human GalNAc-T2, a retaining glycosyltransferase, which initiates the biosynthesis of mucin-type O-glycans. Importantly, we have characterized a hydrogen bond between the beta-phosphate of UDP and the backbone amide group from the Thr7 of the sugar acceptor (EA2 peptide) that promotes catalysis and that we propose could be a general catalytic strategy used in peptide O-glycosylation by retaining glycosyl-transferases. Additional important substrate-substrate interactions have been identified, for example, between the beta-phosphate of UDP with the attacking hydroxyl group from the acceptor substrate and with the substituent at the C2' position of the transferred sugar. Our results support a front-side attack mechanism for this enzyme, with a barrier height of similar to 20 kcal mol(-1) at the QM(M05-2X/TZVP//BP86/SVP)/CHARMM22 level, in reasonable agreement with the experimental kinetic data. Experimental and in silico mutations show that transferase activity is very sensitive to changes in residues Glu334, Asn335 and Arg362. Additionally, our calculations for different donor substrates suggest that human GalNAc-T2 would be inactive if 2'-deoxy-Gal or 2'-oxymethyl-Gal were used, while UDP-Gal is confirmed as a valid sugar donor. Finally, the analysis herein presented highlights that both the substrate-substrate and the enzyme-substrate interactions are mainly concentrated on stabilizing the negative charge developing at the UDP leaving group as the transition state is approached, identifying this as a key aspect of retaining glycosyltransferases catalysis. C1 [Gomez, Hansel; Lluch, Jose M.; Masgrau, Laura] Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain. [Gomez, Hansel; Lluch, Jose M.] Univ Autonoma Barcelona, Dept Quim, E-08193 Barcelona, Spain. [Rojas, Raul; Patel, Divya; Tabak, Lawrence A.] Natl Inst Dent & Craniofacial Res, Sect Biol Chem, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tabak, LA (reprint author), Natl Inst Dent & Craniofacial Res, Sect Biol Chem, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM Lawrence.Tabak@nih.gov; Laura.Masgrau@uab.cat RI Lluch, Jose M./K-1916-2014; Gomez Martinez, Hansel/B-9612-2015; Masgrau, Laura/O-1214-2015 OI Lluch, Jose M./0000-0002-7536-1869; Gomez Martinez, Hansel/0000-0002-5524-1958; Masgrau, Laura/0000-0003-4495-508X FU Spanish "Ministerio de Economia y Competitividad" [CTQ2011-24292]; "Ramon y Cajal" program; "Generalitat de Catalunya", project [2009SGR409]; NIDCR, NIH FX The authors wish to acknowledge Dr A. Milac for providing the coordinates of the starting model for the calculations and also Dr T. Fritz and Dr Jaya Raman for helpful discussions. We acknowledge financial support from the Spanish "Ministerio de Economia y Competitividad" through project CTQ2011-24292 and the "Ramon y Cajal" program (L. M.), and from the "Generalitat de Catalunya", project 2009SGR409, and the intramural program of NIDCR, NIH. NR 77 TC 18 Z9 18 U1 2 U2 19 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 EI 1477-0539 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2014 VL 12 IS 17 BP 2645 EP 2655 DI 10.1039/c3ob42569j PG 11 WC Chemistry, Organic SC Chemistry GA AE7TW UT WOS:000334202900003 PM 24643241 ER PT J AU Prasad, V Cifu, A AF Prasad, Vinay Cifu, Adam TI ''Eliminating chronic kidney disease ... as a diagnosis''. SO POLSKIE ARCHIWUM MEDYCYNY WEWNETRZNEJ-POLISH ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 [Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Cifu, Adam] Univ Chicago, Sect Gen Internal Med, Dept Med, Pritzker Sch Med, Chicago, IL 60637 USA. RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr 10-12N226, Bethesda, MD 20892 USA. EM vinayak.prasad@nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU MEDYCYNA PRAKTYCZNA PI KRAKOW PA UL KRAKOWSKA 41, KRAKOW, 31-066, POLAND SN 0032-3772 J9 POL ARCH MED WEWN JI Pol. Arch. Med. Wewn. PY 2014 VL 124 IS 4 BP 214 EP 214 DI 10.1001/jama.2012.120 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AF2AD UT WOS:000334514100011 PM 24732318 ER PT J AU Yang, K Zhu, L Nie, LM Sun, XL Cheng, L Wu, CX Niu, G Chen, XY Liu, Z AF Yang, Kai Zhu, Lei Nie, Liming Sun, Xiaolian Cheng, Liang Wu, Chenxi Niu, Gang Chen, Xiaoyuan Liu, Zhuang TI Visualization of Protease Activity In Vivo Using an Activatable Photo-Acoustic Imaging Probe Based on CuS Nanoparticles SO THERANOSTICS LA English DT Article DE Peptide; Photoacoustic imaging; Enzyme cleavage; Copper sulfide; MMPs detection ID PHOTOTHERMAL ABLATION THERAPY; LIVING MICE; MATRIX METALLOPROTEINASES; CARBON NANOTUBES; AGENTS; SENSITIVITY; TOMOGRAPHY; GRAPHENE AB Herein, we for the first time report a novel activatable photoacoustic (PA) imaging nano-probe for in vivo detection of cancer-related matrix metalloproteinases (MMPs). A black hole quencher 3 (BHQ3) which absorbs red light is conjugated to near-infrared (NIR)-absorbing copper sulfide (CuS) nanoparticles via a MMP-cleavable peptide linker. The obtained CuS-peptide-BHQ3 (CPQ) nano-probe exhibits two distinctive absorption peaks at 630 nm and 930 nm. Inside the tumor microenviorment where MMPs present, the MMP-sensitive peptide would be cleaved, releasing BHQ3 from the CuS nanoparticles, the former of which as a small molecule is then rapidly cleared out from the tumor, whereas the latter of which as large nanoparticles would retain inside the tumor for a much longer period of time. As the result, the PA signal at 680 nm which is contributed by BHQ3 would be quickly diminished while that at 930 nm would be largely retained. The PA signal ratio of 680 nm /930 nm could thus serve as an in vivo indicator of MMPs activity inside the tumor. Our work presents a novel strategy of in vivo sensing of MMPs based on PA imaging, which should offer remarkably improved detection depth compared with traditional optical imaging techniques. C1 [Yang, Kai; Cheng, Liang; Liu, Zhuang] Soochow Univ, Inst Funct Nano & Soft Mat FUNSOM, Suzhou 215123, Jiangsu, Peoples R China. [Yang, Kai; Zhu, Lei; Nie, Liming; Sun, Xiaolian; Wu, Chenxi; Niu, Gang; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. [Zhu, Lei] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Peoples R China. RP Chen, XY (reprint author), NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov; zliu@suda.edu.cn RI Nie, Liming/F-7718-2016; Zhu, Lei/P-9786-2016 OI Zhu, Lei/0000-0002-1820-4795 FU National "973" Program of China [2011CB911002, 2012CB932601, 2013CB733802, 2014CB744503]; National Natural Science Foundation of China [51002100, 51072126, 51373144, 81371596]; Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), NCI), National Institutes of Health (NIH); China scholarship Council (CSC) FX This work was partially supported by the National "973" Program of China (2011CB911002, 2012CB932601, 2013CB733802, 2014CB744503), the National Natural Science Foundation of China (51002100, 51072126, 51373144, 81371596), and the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), NCI), National Institutes of Health (NIH). Kai Yang was supported by a scholarship from the China scholarship Council (CSC). NR 27 TC 39 Z9 39 U1 16 U2 132 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2014 VL 4 IS 2 BP 134 EP 141 DI 10.7150/thno.7217 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AF4EG UT WOS:000334663600002 PM 24465271 ER PT J AU Bond, SR Baxevanis, AD AF Bond, S. R. Baxevanis, A. D. TI Reconstructing the evolution of ancestral gap junction proteins SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 03-07, 2014 CL Austin, TX SP Soc Integrat & Comparat Biol C1 [Bond, S. R.; Baxevanis, A. D.] NHGRI, Genome Technol Branch, Div Intramural Res, NIH, Bethesda, MD USA. EM steve.bond@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 EI 1557-7023 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PY 2014 VL 54 SU 1 BP E244 EP E244 PG 1 WC Zoology SC Zoology GA AD2FP UT WOS:000333049502038 ER PT J AU Chibucos, K Wendling, A Burgess, HA AF Chibucos, K. Wendling, A. Burgess, H. A. TI Coding of postural information by otoliths in larval zebrafish SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 03-07, 2014 CL Austin, TX SP Soc Integrat & Comparat Biol C1 [Chibucos, K.; Wendling, A.; Burgess, H. A.] Eunice K Shriver Natl Inst Child Hlth & Human Dev, Bethesda, MD USA. EM kandice.chibucos@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 EI 1557-7023 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PY 2014 VL 54 SU 1 BP E36 EP E36 PG 1 WC Zoology SC Zoology GA AD2FP UT WOS:000333049500144 ER PT J AU Koch, BJ Schnitzler, CE Gildea, DE Henry, JQ Martindale, MQ Baxevanis, AD Browne, WE AF Koch, B. J. Schnitzler, C. E. Gildea, D. E. Henry, J. Q. Martindale, M. Q. Baxevanis, A. D. Browne, W. E. TI Differential Gene Expression During Early Embryogenesis in the Ctenophore Mnemiopsis leidyi SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 03-07, 2014 CL Austin, TX SP Soc Integrat & Comparat Biol C1 NHGRI, Bethesda, MD USA. NIH, Bethesda, MD USA. Univ Illinois, Urbana, IL USA. Whitney Lab Marine Biosci, St Augustine, FL USA. Univ Florida, Gainesville, FL 32611 USA. Univ Miami, Coral Gables, FL 33124 USA. EM bernard.koch@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 EI 1557-7023 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PY 2014 VL 54 SU 1 BP E300 EP E300 PG 1 WC Zoology SC Zoology GA AD2FP UT WOS:000333049502261 ER PT J AU Miller, TC Wen, L Chiu, J Shi, YS AF Miller, T. C. Wen, L. Chiu, J. Shi, Y. S. TI Thyroid hormone driving larval cells Mad: the role of c-Myc gene family in intestinal stem cell development SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 03-07, 2014 CL Austin, TX SP Soc Integrat & Comparat Biol C1 [Miller, T. C.; Wen, L.; Chiu, J.; Shi, Y. S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. EM millertc@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 EI 1557-7023 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PY 2014 VL 54 SU 1 BP E140 EP E140 PG 1 WC Zoology SC Zoology GA AD2FP UT WOS:000333049501092 ER PT J AU Presnell, JS Schnitzler, CE Browne, WE AF Presnell, J. S. Schnitzler, C. E. Browne, W. E. TI Klf/Sp transcription factor family expansion, diversification, and innovation in the Unikonta SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 03-07, 2014 CL Austin, TX SP Soc Integrat & Comparat Biol C1 Univ Miami, Coral Gables, FL 33124 USA. NHGRI, NIH, Bethesda, MD 20892 USA. EM j.presnell@umiami.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 EI 1557-7023 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PY 2014 VL 54 SU 1 BP E169 EP E169 PG 1 WC Zoology SC Zoology GA AD2FP UT WOS:000333049501206 ER PT J AU Range, RC Angerer, RC Angerer, LM AF Range, R. C. Angerer, R. C. Angerer, L. M. TI An ancient deuterostome anterior signaling center patterns and sizes the anterior neuroectoderm territory of the sea urchin embryo SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 03-07, 2014 CL Austin, TX SP Soc Integrat & Comparat Biol C1 Mississippi State Univ, Mississippi State, MS USA. NIH, Bethesda, MD USA. EM rangery@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 EI 1557-7023 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PY 2014 VL 54 SU 1 BP E172 EP E172 PG 1 WC Zoology SC Zoology GA AD2FP UT WOS:000333049501220 ER PT J AU Ryan, JF Schnitzler, CE Maxwell, EK Pang, K Francis, WR Smith, SA Wolfsberg, TG Mullikin, JC Haddock, SHD Dunn, CW Martindale, MQ Baxevanis, AD AF Ryan, J. F. Schnitzler, C. E. Maxwell, E. K. Pang, K. Francis, W. R. Smith, S. A. Wolfsberg, T. G. Mullikin, J. C. Haddock, S. H. D. Dunn, C. W. Martindale, M. Q. Baxevanis, A. D. TI The Genome of the Ctenophore Mnemiopsis leidyi: Bringing Resolution to the Phylogenetic Position of the Ctenophores SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 03-07, 2014 CL Austin, TX SP Soc Integrat & Comparat Biol C1 NHGRI, NIH, Bethesda, MD 20892 USA. Sars Intl Ctr Marine Mol Biol, Bergen, Norway. Monterey Bay Aquarium Res Inst, Moss Landing, CA 95039 USA. Brown Univ, Providence, RI 02912 USA. Whitney Lab Marine Biosci, St Augustine, FL 32136 USA. Univ Florida, Gainesville, FL 32611 USA. EM andy@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 EI 1557-7023 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PY 2014 VL 54 SU 1 BP E181 EP E181 PG 1 WC Zoology SC Zoology GA AD2FP UT WOS:000333049501255 ER PT J AU Schnitzler, CE Sanders, SM Plickert, G Seoighe, C Buss, L Wolfsberg, TG Nicotra, M Mullikin, JC Cartwright, P Frank, U Baxevanis, AD AF Schnitzler, C. E. Sanders, S. M. Plickert, G. Seoighe, C. Buss, L. Wolfsberg, T. G. Nicotra, M. Mullikin, J. C. Cartwright, P. Frank, U. Baxevanis, A. D. TI A Tale of Two Hydractinia Genomes: Comparative Genomics of Two Sister Hydrozoan Species SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 03-07, 2014 CL Austin, TX SP Soc Integrat & Comparat Biol C1 NHGRI, NIH, Bethesda, MD USA. Univ Kansas, Lawrence, KS 66045 USA. Univ Cologne, Cologne, Germany. Natl Univ Ireland, Galway, Ireland. Yale Univ, New Haven, CT 06520 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NIH, Intramural Sequencing Ctr, Bethesda, MD USA. EM christine.schnitzler@nih.gov NR 0 TC 0 Z9 0 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 EI 1557-7023 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PY 2014 VL 54 SU 1 BP E186 EP E186 PG 1 WC Zoology SC Zoology GA AD2FP UT WOS:000333049501274 ER PT J AU Du, GW Lewis, MM Sterling, NW Kong, L Chen, HL Mailman, RB Huang, XM AF Du, Guangwei Lewis, Mechelle M. Sterling, Nicholas W. Kong, Lan Chen, Honglei Mailman, Richard B. Huang, Xuemei TI Microstructural changes in the substantia nigra of asymptomatic agricultural workers SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Parkinson's disease (PD); Substantia nigra (SN); Diffusion tensor imaging (DTI); Pesticides; Paraquat; Magnetic resonance imaging (MRI) ID ORGANIC CATION TRANSPORTER-3; PARKINSONS-DISEASE; PARAQUAT NEUROTOXICITY; CLINICAL-DIAGNOSIS; NEURODEGENERATION; PESTICIDES; RISK; DEGENERATION; ACCURACY; EXPOSURE AB Parkinson's disease (PD) is marked by the loss of dopamine neurons in the substantia nigra (SN). Although the exact etiology is unknown, sporadic PD is hypothesized to be a result of genetic susceptibility interacting with environmental insult. Epidemiological studies suggest that pesticide exposure is linked to higher PD risk, but there are no studies demonstrating SN changes with chronic pesticide exposure in human subjects. Thus, high resolution T2-weighted magnetic resonance imaging (MRI) and diffusion tensor (DTI) images were obtained from 12 agricultural workers with chronic pesticide exposure, 12 controls, and 12 PD subjects. Neither controls nor pesticide-exposed subjects, had any parkinsonian symptoms. Exposure history to pesticides was assessed by a structured questionnaire. DTI measures in the SN, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were obtained for all subjects and compared among groups. Compared to controls, PD patients showed the expected significant changes in all DTI measurements in the SN. The pesticide-exposed subjects, compared to controls, had significantly lower FA values (p = 0.022, after multiple comparisons correction), but no significant differences in RD, MD, or AD measures. The study is the first to demonstrate microstructural changes in the SN of human subjects with chronic pesticide exposure. The changes detected by MRI may mark "one of the hits" leading to PD, and underlie the increased risk of PD in pesticide users found in epidemiological studies. Further human studies assisted by these imaging markers may be useful in understanding the etiology of PD. (C) 2013 Elsevier Inc. All rights reserved. C1 [Du, Guangwei; Lewis, Mechelle M.; Sterling, Nicholas W.; Mailman, Richard B.; Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA. [Lewis, Mechelle M.; Mailman, Richard B.; Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Hershey, PA 17033 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Radiol, Hershey, PA 17033 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA 17033 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Kinesiol, Hershey, PA 17033 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Bioengn, Hershey, PA 17033 USA. [Kong, Lan] Penn State Univ, Milton S Hershey Med Ctr, Dept Publ Hlth Sci, Hershey, PA 17033 USA. [Chen, Honglei] NIEHS, Res Triangle Pk, NC 27705 USA. RP Huang, XM (reprint author), Penn State Hershey Med Ctr, 500 Univ Dr,H-037, Hershey, PA 17033 USA. EM xuemei@psu.edu OI Mailman, Richard/0000-0003-1353-2738; Chen, Honglei/0000-0003-3446-7779 FU National Institutes of Health [NS060722, ES019672, NS082151]; Hershey Medical Center GCRC [NIH M01RR10732]; GCRC Construction Grant [C06RR016499]; National Center for Advancing Translational Sciences [UL1 TR000127]; Intramural Research Program of the NIH; National Institute of Environmental Health Sciences FX This work was funded by the National Institutes of Health (NS060722, ES019672, and NS082151), the Hershey Medical Center GCRC (NIH M01RR10732) and GCRC Construction Grant (C06RR016499), and the National Center for Advancing Translational Sciences (UL1 TR000127). Dr. Chen is funded by the Intramural Research Program of the NIH, the National Institute of Environmental Health Sciences. NR 39 TC 5 Z9 6 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 EI 1872-9738 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2014 VL 41 BP 60 EP 64 DI 10.1016/j.ntt.2013.12.001 PG 5 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA AE4IW UT WOS:000333947100009 PM 24334261 ER PT S AU Malech, HL DeLeo, FR Quinn, MT AF Malech, Harry L. DeLeo, Frank R. Quinn, Mark T. BE Quinn, MT DeLeo, FR TI The Role of Neutrophils in the Immune System: An Overview SO NEUTROPHIL METHODS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Polymorphonuclear leukocyte; Granulocyte; Neutrophil methods ID POLYMORPHONUCLEAR LEUKOCYTES; NADPH OXIDASE; GENE-EXPRESSION; BONE MARROW; PROTEIN; ACTIVATION; PHAGOCYTOSIS; SUPEROXIDE; GRANULES; INFLAMMATION AB Neutrophils, also known as polymorphonuclear leukocytes (PMNs), have long been considered as the short-lived, nonspecific white cells that form pus-and also happen to kill invading microbes. Indeed, neutrophils were often neglected (and largely not considered) as immune cells. This historic view of neutrophils has changed considerably over the past several decades, and we know now that, in addition to playing the predominant role in the clearance of bacteria and fungi, they play a major role in shaping the host response to infection and immune system homeostasis. The change in our view of the role of neutrophils in the immune system has been due in large part to the study of these cells in vitro. Such work has been made possible by new and/or improved methods and approaches used to investigate neutrophils. These methods are the focus of this volume. C1 [Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. [Quinn, Mark T.] Montana State Univ, Dept Microbiol & Immunol, Bozeman, MT 59717 USA. RP Malech, HL (reprint author), NIAID, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. OI Malech, Harry/0000-0001-5874-5775; DeLeo, Frank/0000-0003-3150-2516 NR 48 TC 3 Z9 3 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-844-7; 978-1-62703-845-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1124 BP 3 EP 10 DI 10.1007/978-1-62703-845-4_1 D2 10.1007/978-1-62703-845-4 PG 8 WC Genetics & Heredity; Infectious Diseases SC Genetics & Heredity; Infectious Diseases GA BA0WD UT WOS:000332318500002 PM 24504942 ER PT S AU Quinn, MT DeLeo, FR AF Quinn, Mark T. DeLeo, Frank R. BE Quinn, MT DeLeo, FR TI Neutrophil Methods and Protocols Second Edition Preface SO NEUTROPHIL METHODS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Editorial Material; Book Chapter C1 [Quinn, Mark T.] Montana State Univ, Dept Microbiol & Immunol, Bozeman, MT 59717 USA. [DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Quinn, MT (reprint author), Montana State Univ, Dept Microbiol & Immunol, Bozeman, MT 59717 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-844-7; 978-1-62703-845-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1124 BP VII EP VIII D2 10.1007/978-1-62703-845-4 PG 2 WC Genetics & Heredity; Infectious Diseases SC Genetics & Heredity; Infectious Diseases GA BA0WD UT WOS:000332318500001 ER PT S AU Siemsen, DW Malachowa, N Schepetkin, IA Whitney, AR Kirpotina, LN Lei, BF DeLeo, FR Quinn, MT AF Siemsen, Daniel W. Malachowa, Natalia Schepetkin, Igor A. Whitney, Adeline R. Kirpotina, Liliya N. Lei, Benfang DeLeo, Frank R. Quinn, Mark T. BE Quinn, MT DeLeo, FR TI Neutrophil Isolation from Nonhuman Species SO NEUTROPHIL METHODS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Inflammation; Phagocytosis; Large animal model; Granulocyte; Polymorphonuclear leukocyte; Cell isolation; Flow cytometry; Blood; Bone marrow ID WHOLE-BLOOD; FLOW-CYTOMETRY; EXPRESSION; PURIFICATION; DENSITY AB The development of new advances in the understanding of neutrophil biochemistry requires effective procedures for isolating purified neutrophil populations. Although methods for human neutrophil isolation are now standard, similar procedures for isolating neutrophils from many of the nonhuman species used to model human diseases are not as well developed. Since neutrophils are reactive cells, the method of isolation is extremely important to avoid isolation technique-induced alterations in cell function. We present methods here for reproducibly isolating highly purified neutrophils from large animals (bovine, equine, ovine), small animals (murine and rabbit), and nonhuman primates (cynomolgus macaques), and describe optimized details for obtaining the highest cell purity, yield, and viability. We also describe methods to verify phagocytic capacity in the purified cell populations using a flow cytometry-based phagocytosis assay. C1 [Siemsen, Daniel W.; Schepetkin, Igor A.; Kirpotina, Liliya N.; Lei, Benfang] Montana State Univ, Dept Immunol & Infect Dis, Bozeman, MT 59717 USA. [Malachowa, Natalia; Whitney, Adeline R.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. [Quinn, Mark T.] Montana State Univ, Dept Microbiol & Immunol, Bozeman, MT 59717 USA. RP Siemsen, DW (reprint author), Montana State Univ, Dept Immunol & Infect Dis, Bozeman, MT 59717 USA. OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS; NIGMS NIH HHS [GM103500] NR 15 TC 6 Z9 7 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-844-7; 978-1-62703-845-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1124 BP 19 EP 37 DI 10.1007/978-1-62703-845-4_3 D2 10.1007/978-1-62703-845-4 PG 19 WC Genetics & Heredity; Infectious Diseases SC Genetics & Heredity; Infectious Diseases GA BA0WD UT WOS:000332318500004 PM 24504944 ER PT S AU Sweeney, CL Merling, RK Choi, U Priel, DL Kuhns, DB Wang, HM Malech, HL AF Sweeney, Colin L. Merling, Randall K. Choi, Uimook Priel, Debra Long Kuhns, Douglas B. Wang, Hongmei Malech, Harry L. BE Quinn, MT DeLeo, FR TI Generation of Functionally Mature Neutrophils from Induced Pluripotent Stem Cells SO NEUTROPHIL METHODS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE iPSCs; Neutrophils; Giemsa stain; Dihydrorhodamine 123; Staphylocidal assay; Thioglycollate mobilization ID CHRONIC GRANULOMATOUS-DISEASE; HEMATOPOIETIC DIFFERENTIATION AB Induced pluripotent stem cells (iPSCs) are pluripotent stem cells established from somatic cells. The capability of iPSCs to differentiate into any mature cell lineage under the appropriate conditions allows for modeling of cell processes as well as disease states. Here, we describe an in vitro method for generating functional mature neutrophils from human iPSCs. We also describe assays for testing these differentiated cells for neutrophil characteristics and functions by morphology, cell surface markers, production of reactive oxygen species, microbial killing, and mobilization of neutrophils to an inflammatory site in an in vivo immunodeficient mouse infusion model. C1 [Sweeney, Colin L.; Merling, Randall K.; Choi, Uimook; Wang, Hongmei; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Priel, Debra Long; Kuhns, Douglas B.] Frederick Natl Lab Canc Res, Neutrophil Monitoring Lab, Applied Dev Res Directorate, Frederick, MD USA. RP Sweeney, CL (reprint author), NIAID, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. OI Malech, Harry/0000-0001-5874-5775 FU Intramural NIH HHS NR 21 TC 6 Z9 6 U1 2 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-844-7; 978-1-62703-845-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1124 BP 189 EP 206 DI 10.1007/978-1-62703-845-4_12 D2 10.1007/978-1-62703-845-4 PG 18 WC Genetics & Heredity; Infectious Diseases SC Genetics & Heredity; Infectious Diseases GA BA0WD UT WOS:000332318500013 PM 24504953 ER PT S AU Lam, PY Fischer, RS Shin, WD Waterman, CM Huttenlocher, A AF Lam, Pui-ying Fischer, Robert S. Shin, William D. Waterman, Clare M. Huttenlocher, Anna BE Quinn, MT DeLeo, FR TI Spinning Disk Confocal Imaging of Neutrophil Migration in Zebrafish SO NEUTROPHIL METHODS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Spinning disk; Confocal microscopy; Neutrophils; Migration; In vivo imaging; Zebrafish ID TRANSGENIC ZEBRAFISH; IN-VIVO; INFLAMMATION; MICROSCOPY; PERFORMANCE; FISH AB Live-cell imaging techniques have been substantially improved due to advances in confocal microscopy instrumentation coupled with ultrasensitive detectors. The spinning disk confocal system is capable of generating images of fluorescent live samples with broad dynamic range and high temporal and spatial resolution. The ability to acquire fluorescent images of living cells in vivo on a millisecond timescale allows the dissection of biological processes that have not previously been visualized in a physiologically relevant context. In vivo imaging of rapidly moving cells such as neutrophils can be technically challenging. In this chapter, we describe the practical aspects of imaging neutrophils in zebrafish embryos using spinning disk confocal microscopy. Similar setups can also be applied to image other motile cell types and signaling processes in translucent animals or tissues. C1 [Lam, Pui-ying] Univ Wisconsin, Program Cellular & Mol Biol, Madison, WI 53706 USA. [Fischer, Robert S.; Shin, William D.; Waterman, Clare M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Huttenlocher, Anna] Univ Wisconsin, Sch Med, Dept Pediat, Madison, WI USA. [Huttenlocher, Anna] Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA. RP Lam, PY (reprint author), Univ Wisconsin, Program Cellular & Mol Biol, Madison, WI 53706 USA. OI Waterman, Clare/0000-0001-6142-6775 FU NCI NIH HHS [P30 CA014520]; NIGMS NIH HHS [R01 GM074827, GM074827] NR 20 TC 3 Z9 3 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-844-7; 978-1-62703-845-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1124 BP 219 EP 233 DI 10.1007/978-1-62703-845-4_14 D2 10.1007/978-1-62703-845-4 PG 15 WC Genetics & Heredity; Infectious Diseases SC Genetics & Heredity; Infectious Diseases GA BA0WD UT WOS:000332318500015 PM 24504955 ER PT S AU Kobayashi, SD Sturdevant, DE DeLeo, FR AF Kobayashi, Scott D. Sturdevant, Daniel E. DeLeo, Frank R. BE Quinn, MT DeLeo, FR TI Genome-Scale Transcript Analyses with Human Neutrophils SO NEUTROPHIL METHODS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Neutrophil; Microarray; Gene expression; Affymetrix; Transcript; Phagocyte; Polymorphonuclear leukocytes ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; APOPTOSIS-DIFFERENTIATION PROGRAM; CHAIN GENE-EXPRESSION; CYTOCHROME-B HEAVY; BACTERIAL LIPOPOLYSACCHARIDE; PHAGOCYTOSIS; RNA; GRANULOCYTES; ACTIVATION; PATHOGENS AB Transcriptome analyses of single- and multicellular organisms have changed fundamental understanding of biological and pathological processes across multiple scientific disciplines. Over the past decade, studies of polymorphonuclear leukocyte (PMN or neutrophil) gene expression on a global scale have provided new insight into the molecular processes that promote resolution of infections in humans. Herein we present methods to analyze gene expression in human neutrophils using Affymetrix oligonucleotide microarrays, which include isolation of high-quality RNA, generation and labeling of cRNA, and GeneChip hybridization and scanning. Notably, the procedures utilize commercially available reagents and materials and thus represent a standardized approach for evaluating PMN transcript levels. C1 [Kobayashi, Scott D.] Univ Idaho, Dept Microbiol Mol Biol & Biochem, Moscow, ID 83843 USA. [Sturdevant, Daniel E.] NIAID, Genom Unit, Rocky Mt Labs, NIH, Hamilton, MT USA. [DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Kobayashi, SD (reprint author), Univ Idaho, Dept Microbiol Mol Biol & Biochem, Moscow, ID 83843 USA. OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS NR 27 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-844-7; 978-1-62703-845-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1124 BP 437 EP 450 DI 10.1007/978-1-62703-845-4_26 D2 10.1007/978-1-62703-845-4 PG 14 WC Genetics & Heredity; Infectious Diseases SC Genetics & Heredity; Infectious Diseases GA BA0WD UT WOS:000332318500027 PM 24504967 ER PT S AU Elloumi, HZ Holland, SM AF Elloumi, Houda Zghal Holland, Steven M. BE Quinn, MT DeLeo, FR TI Diagnostic Assays for Chronic Granulomatous Disease and Other Neutrophil Disorders SO NEUTROPHIL METHODS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Chronic granulomatous disease (CGD); Chemiluminescence; Leukocyte adhesion deficiency (LAD); Neutropenia; Nitroblue tetrazolium; Reactive oxygen species; Superoxide ID SUPEROXIDE ANION PRODUCTION; RESPIRATORY BURST; PRENATAL-DIAGNOSIS; TETRAZOLIUM SALT; FLOW-CYTOMETRY; OXYGEN; ACTIVATION; CELLS; CHEMILUMINESCENCE; DEFICIENCIES AB Inasmuch as neutrophils are the primary cellular defense against bacterial and fungal infections, disorders that affect these white cells typically predispose individuals to severe and recurrent infections. Therefore, diagnosis of such disorders is an important first step in directing long-term treatment/care for the patient. Herein, we describe methods to identify chronic granulomatous disease, leukocyte adhesion deficiency, and neutropenia. The assays are relatively simple to perform and cost effective and can be performed with equipment available in most laboratories. C1 [Elloumi, Houda Zghal; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Elloumi, HZ (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 49 TC 2 Z9 3 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-844-7; 978-1-62703-845-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1124 BP 517 EP 535 DI 10.1007/978-1-62703-845-4_31 D2 10.1007/978-1-62703-845-4 PG 19 WC Genetics & Heredity; Infectious Diseases SC Genetics & Heredity; Infectious Diseases GA BA0WD UT WOS:000332318500032 PM 24504972 ER PT S AU Carmona-Rivera, C Kaplan, MJ AF Carmona-Rivera, Carmelo Kaplan, Mariana J. BE Eggleton, P Ward, FJ TI Detection of SLE Antigens in Neutrophil Extracellular Traps (NETs) SO SYSTEMIC LUPUS ERYTHEMATOSUS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Leukocytes; Nuclear components; Granular proteins; Reactive oxygen species ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; ANTIBODIES; AUTOANTIBODIES; MYELOPEROXIDASE; PREVALENCE; ELASTASE; ANCA AB Neutrophils are sentinel cells of the innate immune system with a primary role of clearing extracellular pathogens. The release of weblike structures decorated with granular proteins called neutrophil extracellular traps (NETs) has recently been implicated in the pathogenesis of inflammatory and autoimmune diseases. Indeed, NETs may represent an important source of autoantigens and immunostimulatory proteins in systemic lupus erythematosus (SLE). In this chapter, we describe protocols to isolate human peripheral neutrophils, to generate and isolate NETs, and to detect SLE antigens in NETs using immunofluorescence and immunoblot. C1 [Carmona-Rivera, Carmelo; Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Carmona-Rivera, C (reprint author), NIAMSD, Syst Autoimmun Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [T32 AR007080] NR 23 TC 4 Z9 4 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-0325-2; 978-1-4939-0326-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1134 BP 151 EP 161 DI 10.1007/978-1-4939-0326-9_11 D2 10.1007/978-1-4939-0326-9 PG 11 WC Immunology; Pathology SC Immunology; Pathology GA BA0WB UT WOS:000332317100013 PM 24497360 ER PT J AU Martucci, VL Pacak, K AF Martucci, Victoria L. Pacak, Karel TI Pheochromocytoma and paraganglioma: Diagnosis, genetics, management, and treatment SO CURRENT PROBLEMS IN CANCER LA English DT Article ID MITOCHONDRIAL COMPLEX-II; POSITRON-EMISSION-TOMOGRAPHY; GLOMUS-JUGULARE TUMORS; HIPPEL-LINDAU-SYNDROME; SUCCINATE-DEHYDROGENASE GENES; CARNEY-STRATAKIS-SYNDROME; SCALED SCORE PASS; SHOCK-PROTEIN 90; SUBUNIT-B GENE; MALIGNANT PHEOCHROMOCYTOMA C1 [Martucci, Victoria L.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Adult & Reprod Endocrinol, NIH, Bethesda, MD 20892 USA. RP Martucci, VL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Adult & Reprod Endocrinol, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA HD008735-13] NR 246 TC 30 Z9 32 U1 3 U2 13 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-0272 EI 1535-6345 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD JAN-FEB PY 2014 VL 38 IS 1 BP 7 EP 41 DI 10.1016/j.currproblcancer.2014.01.001 PG 35 WC Oncology SC Oncology GA AD9FH UT WOS:000333569700002 PM 24636754 ER PT J AU Ovejero, D Collins, MT AF Ovejero, Diana Collins, Michael T. TI RAS in FGF23: Another Piece in the Puzzle SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID DOMINANT HYPOPHOSPHATEMIC RICKETS; X-LINKED HYPOPHOSPHATEMIA; VITAMIN-D METABOLISM; GROWTH-FACTOR 23; FIBROUS DYSPLASIA; PHOSPHATE; MICE; MUTATIONS; FGF-23; PHENOTYPE C1 [Ovejero, Diana] Univ Autonoma Barcelona, Dept Med, Bellaterra 08193, Spain. [Ovejero, Diana; Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Collins, MT (reprint author), Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, 30 Convent Dr,Bldg 30,Room 228,MSC 4320, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 22 TC 2 Z9 2 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2014 VL 99 IS 1 BP 63 EP 66 DI 10.1210/jc.2013-4290 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD6WP UT WOS:000333402200037 PM 24384015 ER PT J AU Pakkila, F Mannisto, T Pouta, A Hartikainen, AL Ruokonen, A Surcel, HM Bloigu, A Vaarasmaki, M Jarvelin, MR Moilanen, I Suvanto, E AF Pakkila, Fanni Mannisto, Tuija Pouta, Anneli Hartikainen, Anna-Liisa Ruokonen, Aimo Surcel, Helja-Marja Bloigu, Aini Vaarasmaki, Marja Jarvelin, Marjo-Riitta Moilanen, Irma Suvanto, Eila TI The Impact of Gestational Thyroid Hormone Concentrations on ADHD Symptoms of the Child SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; EARLY-PREGNANCY; IODINE PROPHYLAXIS; ENDEMIC GOITER; GENERATION R; DEFICIENCY; POPULATION; FINLAND; MODERATE; MOTHERS AB Context: Maternal hypothyroidism during pregnancy is associated with adverse neuropsychological development in the offspring. Objective: The objective of the study was to evaluate the effect of maternal thyroid dysfunction during pregnancy on a child's attention-deficit/hyperactivity disorder (ADHD) symptoms. Design, Settings, and Participants: The prospective, population-based Northern Finland Birth Cohort 1986 (9362 pregnancies; 9479 infants) included analysis of maternal TSH, free T-4, and thyroid-peroxidase antibodies (TPO-Abs) from early pregnancy samples (5791 women). Teachers evaluated the children's ADHD symptoms at 8 years using the Rutter B2 scale (5131 mother-child pairs), in which a high score indicated probable psychiatric disorders and three questions focused directly on ADHD. Main outcome measures: The odds ratios (ORs) and 95% confidence intervals (95% CIs) of child having ADHD symptoms and/or a high Rutter B2 score after exposure to increases in maternal TSH levels (after logarithmic transformation), low free T-4 levels, and TPO-Ab positivity was tested with logistic regression, adjusting for maternal/family covariates. Data were stratified by the child's gender due to interaction. Results: Among girls the odds of inattention (OR 1.18,95% CI 1.02-1.37), high Rutter B2 total score (OR 1.23, 95% CI 1.03-1.48), and combined ADHD symptoms (OR 1.39, 95% CI 1.07-1.80) significantly increased with every natural log increase in maternal TSH concentrations. Such findings were not evident in boys. No associations were seen between ADHD symptoms and low maternal free T-4 levels or TPO-Ab positivity. Conclusions: Increases in maternal TSH in early pregnancy showed weak but significant association with girls' ADHD symptoms. C1 Univ Oulu, Dept Obstet & Gynecol, Oulu 90029, Finland. [Ruokonen, Aimo] Univ Oulu, Dept Clin Chem, Oulu 90029, Finland. [Moilanen, Irma] Univ Oulu, Dept Clin Child Psychiat, Oulu 90029, Finland. Oulu Univ Hosp, Oulu 90029, Finland. [Pakkila, Fanni; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu 90220, Finland. [Pakkila, Fanni; Pouta, Anneli; Surcel, Helja-Marja; Bloigu, Aini; Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Children Young People & Families, Helsinki 00271, Finland. [Mannisto, Tuija] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA. [Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London SW7 2AZ, England. RP Suvanto, E (reprint author), Dept Obstet & Gynecol, Post Box 23, Oys Oulu 90029, Finland. EM eila.suvanto@ppshp.fi OI Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Mannisto, Tuija/0000-0002-6382-9153 FU Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Alma and K. A. Snellman Foundation (Oulu, Finland); Jalmari and Rauha Ahokas Foundation (Finland); Northern Ostrobothnia Hospital District (Finland); Finnish Medical Association of Clinical Chemistry; Academy of Finland FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and in part by grants from the Alma and K. A. Snellman Foundation (Oulu, Finland), the Jalmari and Rauha Ahokas Foundation (Finland), the Northern Ostrobothnia Hospital District (Finland), the Finnish Medical Association of Clinical Chemistry, and the Academy of Finland. NR 38 TC 11 Z9 11 U1 2 U2 14 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2014 VL 99 IS 1 BP E1 EP E8 DI 10.1210/jc.2013-2943 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD6WP UT WOS:000333402200001 PM 24384024 ER PT J AU Salpea, P Horvath, A London, E Faucz, FR Vetro, A Levy, I Gourgari, E Dauber, A Holm, IA Morrison, PJ Keil, MF Lyssikatos, C Smith, ED Sanidad, MA Kelly, JC Dai, ZY Mowrey, P Forlino, A Zuffardi, O Stratakis, CA AF Salpea, Paraskevi Horvath, Anelia London, Edra Faucz, Fabio R. Vetro, Annalisa Levy, Isaac Gourgari, Evgenia Dauber, Andrew Holm, Ingrid A. Morrison, Patrick J. Keil, Margaret F. Lyssikatos, Charalampos Smith, Eric D. Sanidad, Marc A. Kelly, Joann C. Dai, Zunyan Mowrey, Philip Forlino, Antonella Zuffardi, Orsetta Stratakis, Constantine A. TI Deletions of the PRKAR1A Locus at 17q24.2-q24.3 in Carney Complex: Genotype-Phenotype Correlations and Implications for Genetic Testing SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NODULAR ADRENOCORTICAL DISEASE; SPOTTY SKIN PIGMENTATION; ENDOCRINE OVERACTIVITY; REGULATORY SUBUNIT; MYXOMAS; MUTATIONS; ABNORMALITIES AB Background: Carney complex (CNC) is a multiple neoplasia syndrome caused by PRKAR1A-inactivating mutations. One-third of the patients, however, have no detectable PRKAR1A coding sequence defects. Small deletions of the gene were previously reported in few patients, but large deletions of the chromosomal PRKAR1A locus have not been studied systematically in a large cohort of patients with CNC. Setting: A tertiary care referral center was the setting for analysis of an international cohort of patients with CNC. Methods: Methods included genome-wide array analysis followed by fluorescent in situ hybridization, mRNA, and other studies as well as a retrospective analysis of clinical information and phenotype-genotype correlation. Results: We detected 17q24.2-q24.3 deletions of varying size that included the PRKAR1A gene in 11 CNC patients (of 51 tested). Quantitative PCR showed that these patients had significantly lower PRKAR1A mRNA levels. Phenotype varied but was generally severe and included manifestations that are not commonly associated with CNC, presumably due to haploinsufficiency of other genes in addition to PRKAR1A. Conclusions: A significant number (21.6%) of patients with CNC that are negative in currently available testing may have PRKAR1A haploinsufficiency due to genomic defects that are not detected by Sanger sequencing. Array-based studies are necessary for diagnostic confirmation of these defects and should be done in patients with unusual and severe phenotypes who are PRKAR1A mutation-negative. C1 [Salpea, Paraskevi; London, Edra; Faucz, Fabio R.; Levy, Isaac; Gourgari, Evgenia; Keil, Margaret F.; Lyssikatos, Charalampos; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Horvath, Anelia] George Washington Univ, Dept Biochem & Mol Med, Washington, DC 20037 USA. [Vetro, Annalisa; Forlino, Antonella; Zuffardi, Orsetta] Univ Pavia, Dept Mol Med, I-27100 Pavia, Italy. [Dauber, Andrew; Holm, Ingrid A.] Boston Childrens Hosp, Div Genet & Endocrinol, Boston, MA USA. [Morrison, Patrick J.] Queens Univ Belfast, Reg Med Genet Ctr, Belfast BT9 7AB, Antrim, North Ireland. [Smith, Eric D.; Sanidad, Marc A.; Kelly, Joann C.; Dai, Zunyan; Mowrey, Philip] Quest Diagnost Nichols Inst, Chantilly, VA 20151 USA. RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH,Clin Res Ctr, 10 Ctr Dr,Bldg 10,Room 1-3330,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov RI Forlino, Antonella/H-5385-2015; OI Forlino, Antonella/0000-0002-6385-1182; zuffardi, orsetta/0000-0002-1466-4559; Vetro, Annalisa/0000-0003-2437-7526 FU Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health FX This work was supported by the Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health. NR 19 TC 10 Z9 10 U1 1 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2014 VL 99 IS 1 BP E183 EP E188 DI 10.1210/jc.2013-3159 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD6WP UT WOS:000333402200027 PM 24170103 ER PT J AU Nguyen, VP Chen, J Petrus, MN Goldman, CK Kruhlak, MJ Bamford, RN Waldmann, TA AF Nguyen, Vinh-Phuc Chen, Jing Petrus, Michael N. Goldman, Carolyn K. Kruhlak, Michael J. Bamford, Richard N. Waldmann, Thomas A. TI A New Domain in the Toll/IL-1R Domain-Containing Adaptor Inducing Interferon-beta Factor Protein Amino Terminus Is Important for Tumor Necrosis Factor-alpha Receptor-Associated Factor 3 Association, Protein Stabilization and Interferon Signaling SO JOURNAL OF INNATE IMMUNITY LA English DT Article DE Innate immunity; Interferon signaling; Protein stability; Tumor necrosis factor-alpha receptor-associated factor 3; Toll/IL-1R domain-containing adaptor inducing interferon-beta factor ID NF-KAPPA-B; PATTERN-RECOGNITION RECEPTORS; IFN-REGULATORY FACTOR-3; TOLL-LIKE RECEPTORS; DENDRITIC CELLS; INNATE IMMUNITY; CUTTING EDGE; ACTIVATION; TRIF; TRAF3 AB Toll/IL-1R domain-containing adaptor inducing interferon-beta (IFN-beta) factor (TRIF) is a key adaptor for Toll-like receptor (TLR) 3 and TLR4 signaling. Using a novel cDNA isolate encoding a TRIF protein with a 21-residue deletion (Delta 60-181) from its amino-terminal half, we investigated the impact of this deletion on TRIF functions. Transfection studies consistently showed higher expression levels of the (Delta 60-181) TRIF compared to wild-type (wt) TRIF, an effect unrelated to apoptosis, cell lines or plasmid amplification. Colocalization of wt and (Delta 60-181) TRIF proteins led to a dramatic reduction of their respective expressions, suggesting that wt/(Delta 60-181) TRIF heterocomplexes are targeted for degradation. We demonstrated that wt TRIF associates with tumor necrosis factor-alpha receptor-associated factor 3 (TRAF3) better than (Delta 60-181) TRIF, culminating in its greater ubiquitination and proteolysis. This explains, in part, the differential expression levels of the two TRIF proteins. Despite higher expression levels in transfected cells, (Delta 60-181) TRIF inefficiently transactivated the IFN pathway, whereas the nuclear factor-kappa B (NE-kappa B) pathway activation remained similar to that by wt TRIF. In coexpression studies, (Delta 60-181) TRIF marginally contributed to the IFN pathway activation, but still enhanced NE-kappa B signaling with wt TRIF. Therefore, this 21 amino acid sequence is crucial for TRAF3 association, modulation of TRIF stability and activation of the IFN pathway. (C) 2014 S. Karger AG, Basel C1 [Nguyen, Vinh-Phuc; Chen, Jing; Petrus, Michael N.; Goldman, Carolyn K.; Waldmann, Thomas A.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kruhlak, Michael J.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Bamford, Richard N.] Transponics, Jacobus, PA USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, NIH, Bldg 10,Room 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM tawald@mail.nih.gov FU National Cancer Institute, National Institutes of Health FX This study was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 54 TC 1 Z9 1 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X EI 1662-8128 J9 J INNATE IMMUN JI J. Innate Immun. PY 2014 VL 6 IS 3 BP 377 EP 393 DI 10.1159/000356408 PG 17 WC Immunology SC Immunology GA AE2AF UT WOS:000333775000013 PM 24577058 ER PT J AU Kuzumaki, N Yamamizu, K Okano, H Narita, M AF Kuzumaki, Naoko Yamamizu, Kohei Okano, Hideyuki Narita, Minoru TI Role of opioid systems in the differentiation potential of pluripotent stem cells SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 87th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 19-21, 2014 CL Sendai, JAPAN SP Japanese Pharmacol Soc C1 [Kuzumaki, Naoko; Narita, Minoru] Hoshi Univ, Dept Pharmacol, Sch Pharm Pharmaceut Sci, Shinagawa Ku, Tokyo 1428501, Japan. [Kuzumaki, Naoko; Okano, Hideyuki] Keio Univ, Dept Physiol, Sch Med, Shinjuku Ku, Tokyo 1608582, Japan. [Yamamizu, Kohei] NIA, NIH, Dev Genom & Aging Sect, Baltimore, MD 21224 USA. [Yamamizu, Kohei] Kyoto Univ, Lab Stem Cell Differentiat, Stem Cell Res Ctr, Inst Frontier Med Sci,Sakyo Ku, Kyoto 6068507, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 EI 1347-8648 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2014 VL 124 SU 1 BP 52P EP 52P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AD8DZ UT WOS:000333498000139 ER PT J AU Horinouchi, Y Summers, FA Ehrenshaft, M Tsuchiya, K Tamaki, T Mason, RP AF Horinouchi, Yuya Summers, Fiona A. Ehrenshaft, Marilyn Tsuchiya, Koichiro Tamaki, Toshiaki Mason, Ronald P. TI Investigating free radical generation in HepG2 cells induced by aromatic amine compounds using immuno-spin trapping SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 87th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 19-21, 2014 CL Sendai, JAPAN SP Japanese Pharmacol Soc C1 [Horinouchi, Yuya] Tokushima Univ Hasp, Dept Pharm, Tokushima 7708503, Japan. [Horinouchi, Yuya; Tamaki, Toshiaki] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Pharmacol, Tokushima 7708503, Japan. [Summers, Fiona A.; Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, Free Radical Metab Grp, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Tsuchiya, Koichiro] Univ Tokushima, Grad Sch, Dept Med Pharmacol, Inst Hlth Biosci, Tokushima 7708505, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 EI 1347-8648 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2014 VL 124 SU 1 BP 176P EP 176P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AD8DZ UT WOS:000333498000609 ER PT J AU Kitanaka, J Kitanaka, N Hal, FS Uhl, GR Tanaka, K Nishiyama, N Tatsuta, T Takemura, M AF Kitanaka, Junichi Kitanaka, Nobue Hal, F. Scott Uhl, George. R. Tanaka, Koh-ichi Nishiyama, Nobuyoshi Tatsuta, Tomohiro Takemura, Motohiko TI Exogenous agmatine inhibits methamphetamine-induced stereotypy and hyperlocomotion in mice SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 87th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 19-21, 2014 CL Sendai, JAPAN SP Japanese Pharmacol Soc C1 [Kitanaka, Junichi; Kitanaka, Nobue; Takemura, Motohiko] Hyogo Coll Med, Dept Pharmacol, Nishinomiya, Hyogo 6638501, Japan. [Hal, F. Scott; Uhl, George. R.] NIDA IRP, Baltimore, MD 21224 USA. [Tanaka, Koh-ichi; Nishiyama, Nobuyoshi] Hyogo Univ Hlth Sci, Sch Pharm, Dept Pharm, Div Pharmacol, Kobe, Hyogo 6508530, Japan. [Tatsuta, Tomohiro] Ibogawa Hosp, Tatsuno, Hyogo 6711688, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 EI 1347-8648 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2014 VL 124 SU 1 BP 218P EP 218P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AD8DZ UT WOS:000333498000777 ER PT J AU Aamann, MD Hvitby, C Popuri, V Muftuoglu, M Lemminger, L Skeby, CK Keijzers, G Ahn, B Bjoras, M Bohr, VA Stevnsner, T AF Aamann, Maria D. Hvitby, Christina Popuri, Venkateswarlu Muftuoglu, Meltem Lemminger, Lasse Skeby, Cecilie K. Keijzers, Guido Ahn, Byungchan Bjoras, Magnar Bohr, Vilhelm A. Stevnsner, Tinna TI Cockayne Syndrome group B protein stimulates NEIL2 DNA glycosylase activity SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE Cockayne Syndrome; CSB; NEIL2; Base excision repair; Oxidative damage ID BASE EXCISION-REPAIR; OXIDATIVELY DAMAGED DNA; RNA-POLYMERASE-II; OXIDIZED BASES; HYDANTOIN LESIONS; CELLULAR REPAIR; UV-IRRADIATION; GENE-PRODUCT; CSB PROTEIN; CELLS AB Cockayne Syndrome is a segmental premature aging syndrome, which can be caused by loss of function of the CSB protein. CSB is essential for genome maintenance and has numerous interaction partners with established roles in different DNA repair pathways including transcription coupled nucleotide excision repair and base excision repair. Here, we describe a new interaction partner for CSB, the DNA glycosylase NEIL2. Using both cell extracts and recombinant proteins, CSB and NEIL2 were found to physically interact independently of DNA. We further found that CSB is able to stimulate NEIL2 glycosylase activity on a 5-hydroxyl uracil lesion in a DNA bubble structure substrate in vitro. A novel 4,6-diamino-5-formamidopyrimidine (FapyA) specific incision activity of NEIL2 was also stimulated by CSB. To further elucidate the biological role of the interaction, immunofluorescence studies were performed, showing an increase in cytoplasmic CSB and NEIL2 co-localization after oxidative stress. Additionally, stalling of the progression of the transcription bubble with et-amanitin resulted in increased co-localization of CSB and NEIL2. Finally, CSB knockdown resulted in reduced incision of 8-hydroxyguanine in a DNA bubble structure using whole cell extracts. Taken together, our data supports a biological role for CSB and NEIL2 in transcription associated base excision repair. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Aamann, Maria D.; Hvitby, Christina; Lemminger, Lasse; Skeby, Cecilie K.; Keijzers, Guido; Ahn, Byungchan; Stevnsner, Tinna] Aarhus Univ, Danish Ctr Mol Gerontol, DK-8000 Aarhus C, Denmark. [Aamann, Maria D.; Hvitby, Christina; Lemminger, Lasse; Skeby, Cecilie K.; Keijzers, Guido; Ahn, Byungchan; Stevnsner, Tinna] Aarhus Univ, Dept Mol Biol & Genet, Danish Aging Res Ctr, DK-8000 Aarhus C, Denmark. [Popuri, Venkateswarlu; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Muftuoglu, Meltem; Keijzers, Guido] Univ Copenhagen, Ctr Hlth Aging, Copenhagen, Denmark. [Ahn, Byungchan] Univ Ulsan, Ulsan, South Korea. [Bjoras, Magnar] Oslo Univ Hosp, Ctr Mol Biol & Neurosci, Mol Biol Lab, Oslo, Norway. RP Stevnsner, T (reprint author), Aarhus Univ, Danish Ctr Mol Gerontol, CF Mollers Alle 3,Bldg 1130, DK-8000 Aarhus C, Denmark. EM tvs@mb.au.dk FU National Institute on Aging, NIH; Velux Foundation; Danish Cancer Society; Norwegian Cancer Society; Nordea Foundation FX The authors thank Ulla Henriksen for providing excellent technical assistance and Rune Thomsen is thanked for technical assistance with the axiovert200m. Susanne T. Veno is thanked for commenting the manuscript. Support was obtained from the Intramural Program of the National Institute on Aging, NIH, the Velux Foundation, the Danish Cancer Society, the Norwegian Cancer Society and the Nordea Foundation. NR 67 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JAN PY 2014 VL 135 BP 1 EP 14 DI 10.1016/j.mad.2013.12.008 PG 14 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA AE1GI UT WOS:000333717400001 PM 24406253 ER PT J AU Holly, AC Pilling, LC Hernandez, D Lee, BP Singleton, A Ferrucci, L Melzer, D Harries, LW AF Holly, Alice C. Pilling, Luke C. Hernandez, Dena Lee, Benjamin P. Singleton, Andrew Ferrucci, Luigi Melzer, David Harries, Lorna W. TI Splicing factor 3B1 hypomethylation is associated with altered SF3B1 transcript expression in older humans SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE Ageing; Splicing; DNA methylation; SF3B1; Epigenetics ID DNA-METHYLATION; GENE-EXPRESSION; HISTONE MODIFICATIONS; CALORIC RESTRICTION; ADVANCING AGE; MUTATIONS; PRE; PATTERNS; DISEASE; SILENCE AB Ageing in man is associated with changes to the splicing factor pool. A proportion of splicing factors are regulated during ageing by mechanisms involving the Ataxia Telangiectasia Mutated (ATM) gene, but the factors that determine the remaining proportion have yet to be identified. DNA methylation is known to be an important regulatory mechanism of gene expression. We assessed age-associated methylation and expression levels for 27 splicing factor genes, in peripheral blood samples from the InCHIANTI study. Examination of splicing patterns at specific loci was examined in a second cohort, the Exeter 10000 study. 27/502 methylation probes in 17 different genes were associated with age. Most changes were not associated with transcript expression levels or splicing patterns, but hypomethylation of the SF3B1 promoter region was found to mediate 53% of the relationship between age and transcript expression at this locus (p = 0.02). DNA methylation does not appear to play a major role in regulation of the splicing factors, but changes in SF3B1 expression may be attributable to promoter hypomethylation at this locus. SF3B1 encodes a critical component of the U2 snRNP; altered expression of this gene may therefore contribute to the loss of regulated mRNA splicing that occurs with age. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Holly, Alice C.; Lee, Benjamin P.; Harries, Lorna W.] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter EX2 5DW, Devon, England. [Pilling, Luke C.; Melzer, David] Univ Exeter, Sch Med, Exeter EX1 2LU, Devon, England. [Hernandez, Dena; Singleton, Andrew] NIA, Lab Neurogenet, Bethesda, MD 20892 USA. [Ferrucci, Luigi] Harbor Hosp, NIA, Clin Res Branch, Baltimore, MD 21225 USA. RP Harries, LW (reprint author), Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter EX2 5DW, Devon, England. EM L.W.Harries@exeter.ac.uk OI Pilling, Luke/0000-0002-3332-8454; Lee, Benjamin/0000-0003-4351-9630; Melzer, David/0000-0002-0170-3838 NR 50 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JAN PY 2014 VL 135 BP 50 EP 56 DI 10.1016/j.mad.2014.01.005 PG 7 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA AE1GI UT WOS:000333717400006 PM 24463145 ER PT J AU Hung, YH Faux, NG Killilea, DW Yanjanin, N Firnkes, S Volitakis, I Ganio, G Walterfang, M Hastings, C Porter, FD Ory, DS Bush, AI AF Hung, Ya Hui Faux, Noel G. Killilea, David W. Yanjanin, Nicole Firnkes, Sally Volitakis, Irene Ganio, George Walterfang, Mark Hastings, Caroline Porter, Forbes D. Ory, Daniel S. Bush, Ashley I. TI Altered transition metal homeostasis in Niemann-Pick disease, type C1 SO METALLOMICS LA English DT Article ID DEFICIENT FERRITIN IMMUNOREACTIVITY; ALZHEIMERS-DISEASE; CHOLESTEROL HOMEOSTASIS; COPPER INCORPORATION; VISCERAL ORGANS; CERULOPLASMIN; MICE; ZINC; GENE; IDENTIFICATION AB The loss of NPC1 protein function is the predominant cause of Niemann-Pick type C1 disease (NP-C1), a systemic and neurodegenerative disorder characterized by late-endosomal/lysosomal accumulation of cholesterol and other lipids. Limited evidence from post-mortem human tissues, an Npc1(-/-) mouse model, and cell culture studies also suggest failure of metal homeostasis in NP-C1. To investigate these findings, we performed a comprehensive transition metal analysis of cerebrospinal fluid (CSF), plasma and tissue samples from human NP-C1 patients and an Npc1(-/-) mouse model. NPC1 deficiency in the Npc1(-/-) mouse model resulted in a perturbation of transition metal homeostasis in the plasma and key organs (brain, liver, spleen, heart, lungs, and kidneys). Analysis of human patient CSF, plasma and post-mortem brain tissues also indicated disrupted metal homeostasis. There was a disparity in the direction of metal changes between the human and the Npc1(-/-) mouse samples, which may reflect species-specific metal metabolism. Nevertheless, common to both species is brain zinc accumulation. Furthermore, treatment with the glucosylceramide synthase inhibitor miglustat, the only drug shown in a controlled clinical trial to have some efficacy for NP-C1, did not correct the alterations in CSF and plasma transition metal and ceruloplasmin (CP) metabolism in NP-C1 patients. These findings highlight the importance of NPC1 function in metal homeostasis, and indicate that metal-targeting therapy may be of value as a treatment for NP-C. C1 [Hung, Ya Hui; Faux, Noel G.; Volitakis, Irene; Ganio, George; Bush, Ashley I.] Univ Melbourne, Oxidat Biol Unit, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3010, Australia. [Killilea, David W.] Childrens Hosp Oakland, Res Inst, Nutr & Metab Ctr, Oakland, CA 94609 USA. [Yanjanin, Nicole; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Firnkes, Sally; Ory, Daniel S.] Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr, St Louis, MO 63110 USA. [Walterfang, Mark] Royal Melbourne Hosp, Neuropsychiat Unit, Melbourne, Vic 3050, Australia. [Walterfang, Mark] Melbourne Neuropsychiat Ctr, Melbourne, Vic 3050, Australia. [Hastings, Caroline] Childrens Hosp & Res Ctr, Oakland, CA 94609 USA. RP Bush, AI (reprint author), Univ Melbourne, Oxidat Biol Unit, Florey Inst Neurosci & Mental Hlth, Level 4,Kenneth Myer Bldg, Parkville, Vic 3010, Australia. EM ashley.bush@florey.edu.au RI Hung, Ya Hui/F-1951-2010; Faux, Noel/C-4423-2011; Bush, Ashley/A-1186-2007 OI Hung, Ya Hui/0000-0002-5440-2764; Faux, Noel/0000-0003-4594-8818; Bush, Ashley/0000-0001-8259-9069 FU National Health & Medical Research Council of Australia; Cooperative Research Centre for Mental Health; Addi and Cassi Fund; Perpetual Trustees (Harry Secomb Foundation and Payne L & Heather Medical Research Charitable Foundation); Ara Parseghian Medical Research Foundation; Dana's Angels Research Trust; NIH Clinical Center and Office of Rare Diseases; Victorian Government; Operational Infrastructure FX This work was supported by grants from the National Health & Medical Research Council of Australia (A.I.B.), Cooperative Research Centre for Mental Health (A.I.B.), the Addi and Cassi Fund (A.I.B. and Y.H.H.), Perpetual Trustees (Harry Secomb Foundation and Payne L & Heather Medical Research Charitable Foundation (A.I.B.)), intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (F.D.P.), Ara Parseghian Medical Research Foundation (D.S.O. and F.D.P.), Dana's Angels Research Trust (D.S.O. and F.D.P.). Bench to Bedside award from the NIH Clinical Center and Office of Rare Diseases (F.D.P.). The Florey Institute of Neuroscience and Mental Health acknowledges the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant. The authors thank Shih-Min Chiu, Amelia Sedjahtera, Lisa Bray, Kali Hubbert, Charlotte Jordan, Tai Holland, and the Australian Imaging, Biomarker and Lifestyle (AIBL) Study research team (Brett Trounson, Christopher Fowler, Rebecca Rumble and Kelly Pertile) for technical support; and Dr Paul Adlard (Florey Institute of Neuroscience and Mental Health) for provision of non-NP-C control CSF samples. The authors would like to thank NP-C patients and their families, and healthy control subjects for their contribution and participation in this study. NR 66 TC 7 Z9 7 U1 0 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1756-5901 EI 1756-591X J9 METALLOMICS JI Metallomics PY 2014 VL 6 IS 3 BP 542 EP 553 DI 10.1039/c3mt00308f PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AD9DU UT WOS:000333565800015 PM 24343124 ER PT J AU Aranko, AS Oeemig, JS Zhou, DW Kajander, T Wlodawer, A Iwai, H AF Aranko, A. Sesilja Oeemig, Jesper S. Zhou, Dongwen Kajander, Tommi Wlodawer, Alexander Iwai, Hideo TI Structure-based engineering and comparison of novel split inteins for protein ligation SO MOLECULAR BIOSYSTEMS LA English DT Article ID TUBERCULOSIS-RECA INTEIN; CRYSTAL-STRUCTURE; MULTIDOMAIN PROTEIN; DNAE INTEIN; ADENOSINE-TRIPHOSPHATASE; MOLECULAR-REPLACEMENT; RECOMBINANT PROTEINS; NOSTOC-PUNCTIFORME; ESCHERICHIA-COLI; SPLICING ELEMENT AB Protein splicing is an autocatalytic process involving self-excision of an internal protein domain, the intein, and concomitant ligation of the two flanking sequences, the exteins, with a peptide bond. Protein splicing can also take place in trans by naturally split inteins or artificially split inteins, ligating the exteins on two different polypeptide chains into one polypeptide chain. Protein trans-splicing could work in foreign contexts by replacing the native extein sequences with other protein sequences. Protein ligation using protein trans-splicing increasingly becomes a useful tool for biotechnological applications such as semi-synthesis of proteins, segmental isotopic labeling, and in vivo protein engineering. However, only a few split inteins have been successfully applied for protein ligation. Naturally split inteins have been widely used, but they are cross-reactive to each other, limiting their applications to multiple-fragment ligation. Based on the three-dimensional structures including two newly determined intein structures, we derived 21 new split inteins from four highly efficient cis-splicing inteins, in order to develop novel split inteins suitable for protein ligation. We systematically compared trans-splicing of 24 split inteins and tested the cross-activities among them to identify orthogonal split intein fragments that could be used in chemical biology and biotechnological applications. C1 [Aranko, A. Sesilja; Oeemig, Jesper S.; Kajander, Tommi; Iwai, Hideo] Univ Helsinki, Inst Biotechnol, Res Program Struct Biol & Biophys, FIN-00014 Helsinki, Finland. [Zhou, Dongwen; Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Iwai, H (reprint author), Univ Helsinki, Inst Biotechnol, Res Program Struct Biol & Biophys, POB 65, FIN-00014 Helsinki, Finland. EM hideo.iwai@helsinki.fi RI Iwai, Hideo/A-6416-2009; Aranko, Aino Sesilja/N-1224-2016; OI Iwai, Hideo/0000-0001-7376-5264; Aranko, Aino Sesilja/0000-0001-9425-3524; Kajander, Tommi/0000-0002-5094-227X FU Viikki Doctoral Programme in Molecular Biosciences; National Doctoral Programme in Informational and Structural Biology; Academy of Finland [137995]; Sigrid Juselius Foundation; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; Biocenter Finland FX We thank C. Albert and S. Ferkau for technical assistance in the protein and plasmid preparations, R. Kolodziejczyk and K. Kogan for collection of diffraction data, and Ivan Shabalin and Wladek Minor (University of Virginia) for assistance with determining the structure of TvoVMADelta 21 intein. A.S.A. acknowledges Viikki Doctoral Programme in Molecular Biosciences for financial support. J.S.O. acknowledges the National Doctoral Programme in Informational and Structural Biology for financial support. This work was supported in part by the Academy of Finland (137995), Sigrid Juselius Foundation, and Biocenter Finland (for H.I., the crystallization, and NMR facilities at the Institute of Biotechnology), and in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 62 TC 7 Z9 7 U1 1 U2 17 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X EI 1742-2051 J9 MOL BIOSYST JI Mol. Biosyst. PY 2014 VL 10 IS 5 BP 1023 EP 1034 DI 10.1039/c4mb00021h PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AD9JL UT WOS:000333581100005 PM 24574026 ER PT J AU Boswell, KL Paris, R Boritz, E Ambrozak, D Yamamoto, T Darko, S Wloka, K Wheatley, A Narpala, S McDermott, A Roederer, M Haubrich, R Connors, M Ake, J Douek, DC Kim, J Petrovas, C Koup, RA AF Boswell, Kristin L. Paris, Robert Boritz, Eli Ambrozak, David Yamamoto, Takuya Darko, Sam Wloka, Kaska Wheatley, Adam Narpala, Sandeep McDermott, Adrian Roederer, Mario Haubrich, Richard Connors, Mark Ake, Julie Douek, Daniel C. Kim, Jerome Petrovas, Constantinos Koup, Richard A. TI Loss of Circulating CD4 T Cells with B Cell Helper Function during Chronic HIV Infection SO PLOS PATHOGENS LA English DT Article ID FOLLICULAR-HELPER; ANTIBODY-RESPONSES; SPARING REGIMENS; GERMINAL-CENTERS; VIRAL-INFECTION; EXPRESSION; DIFFERENTIATION; COMMITMENT; GENERATION; CHEMOKINE AB The interaction between follicular T helper cells (T-FH) and B cells in the lymph nodes and spleen has a major impact on the development of antigen-specific B cell responses during infection or vaccination. Recent studies described a functional equivalent of these cells among circulating CD4 T cells, referred to as peripheral T-FH cells. Here, we characterize the phenotype and in vitro B cell helper activity of peripheral T-FH populations, as well as the effect of HIV infection on these populations. In co-culture experiments we confirmed CXCR5+ cells from HIV-uninfected donors provide help to B cells and more specifically, we identified a CCR7(high)CXCR5(high)CCR6(high)PD-1(high) CD4 T cell population that secretes IL-21 and enhances isotype-switched immunoglobulin production. This population is significantly decreased in treatment-naive, HIV-infected individuals and can be recovered after anti-retroviral therapy. We found impaired immunoglobulin production in co-cultures from HIV-infected individuals and found no correlation between the frequency of peripheral T-FH cells and memory B cells, or with neutralization activity in untreated HIV infection in our cohort. Furthermore, we found that within the peripheral T-FH population, the expression level of T-FH-associated genes more closely resembles a memory, non-T-FH population, as opposed to a T-FH population. Overall, our data identify a heterogeneous population of circulating CD4 T cells that provides in vitro help to B cells, and challenges the origin of these cells as memory T-FH cells. Author Summary Follicular T helper cells (T-FH) interact with B cells within germinal centers of lymphoid tissue to promote the survival, isotype switching and generation of high affinity memory B cells and plasma cells. Recently, a population of circulating CD4 T cells that shares phenotypic and functional characteristics with T-FH cells, named peripheral T-FH cells, has been identified. The relationship between peripheral T-FH cells in the blood and T-FH cells within the lymphoid tissue remains unclear, and whether or not peripheral T-FH cells can provide insight into T cell and B cell dynamics within lymphoid tissue during infection or vaccination is not understood. Here we characterize peripheral T-FH cells and show that unlike T-FH cells, peripheral T-FH cells secrete a diverse array of cytokines and decrease, rather than increase, during chronic HIV infection. Furthermore, we did not observe a relationship between peripheral T-FH cells and memory B cells, or with the production of neutralizing antibodies to HIV. Overall, our data indicate that while peripheral T-FH cells share some characteristics with T-FH cells, they may not represent a good surrogate to study T cell and B cell dynamics within lymphoid tissue. C1 [Boswell, Kristin L.; Paris, Robert; Ambrozak, David; Yamamoto, Takuya; Wloka, Kaska; Petrovas, Constantinos; Koup, Richard A.] Vaccine Res Ctr, Immunol Lab, NIAID, NIH, Bethesda, MD USA. [Paris, Robert; Ake, Julie; Kim, Jerome] United States Mil HIV Res Program, Rockville, MD USA. [Boritz, Eli; Darko, Sam; Douek, Daniel C.] Human Immunol Sect, Vaccine Res Ctr, NIAID, NIH, Bethesda, MD USA. [Wheatley, Adam; Narpala, Sandeep; McDermott, Adrian] Immunol Core Sect, Vaccine Res Ctr, NIAID, NIH, Bethesda, MD USA. [Roederer, Mario] Natl Inst Hlth, ImmunoTechnol Sect, Vaccine Res Ctr, Bethesda, MD USA. [Haubrich, Richard] Univ Calif San Diego, Div Infect Dis, Antiviral Res Ctr, San Diego, CA USA. [Connors, Mark] HIV Specif Immun Sect, Immunoregulat Lab, NIAID, NIH, Bethesda, MD USA. [Boswell, Kristin L.; Paris, Robert; Ambrozak, David; Yamamoto, Takuya; Wloka, Kaska; Petrovas, Constantinos; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Paris, Robert; Ake, Julie; Kim, Jerome] US Mil HIV Res Program, Rockville, MD USA. [Boritz, Eli; Darko, Sam; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Wheatley, Adam; Narpala, Sandeep; McDermott, Adrian] NIAID, Immunol Core Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Roederer, Mario] NIH, ImmunoTechnol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Haubrich, Richard] Univ Calif San Diego, Div Infect Dis, Antiviral Res Ctr, San Diego, CA 92103 USA. [Connors, Mark] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Boswell, KL (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM petrovasc@mail.nih.gov RI Yamamoto, Takuya/L-2642-2013; OI Yamamoto, Takuya/0000-0003-3753-1211; Wheatley, Adam/0000-0002-5593-9387 FU Intramural Research Program of the Vaccine Research Center, NIAID, National Institutes of Health [AI064086]; Bill and Melinda Gates Foundation [OPP1032325]; University of California San Diego Center for AIDS Research; San Diego AIDS Clinical Trial Group [CTU AI69432]; National Medical Center (CNMC) under the auspices of the Basic Science Core of the District of Columbia Developmental Center for AIDS Research; NIAID, NIH [P30AI087714]; U.S. Army Medical Research and Material Command (USAMRMC) [Y1-AI-2642-12]; National Institutes of Allergy and Infectious Diseases; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. [W81XWH-07-2-0067]; U.S. Department of Defense (DOD) FX This research was supported by the Intramural Research Program of the Vaccine Research Center, NIAID, National Institutes of Health (AI064086; RH) and CAVD grant #OPP1032325 from the Bill and Melinda Gates Foundation (RAK), the University of California San Diego Center for AIDS Research (AI36214; RH) and the San Diego AIDS Clinical Trial Group (CTU AI69432; RH). The Children's National Medical Center (CNMC) under the auspices of the Basic Science Core of the District of Columbia Developmental Center for AIDS Research was funded by a grant from NIAID, NIH (P30AI087714). 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 (DOD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The opinions herein are those of the authors and should not be construed as official or representing the views of the U.S. Department of Health and Human Services, National Institute for Allergy and Infectious Diseases, the Department of Defense, or the Department of the Army. NR 40 TC 58 Z9 61 U1 1 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2014 VL 10 IS 1 AR e1003853 DI 10.1371/journal.ppat.1003853 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AC6NQ UT WOS:000332640900001 PM 24497824 ER PT J AU Denton, PW Long, JM Wietgrefe, SW Sykes, C Spagnuolo, RA Snyder, OD Perkey, K Archin, NM Choudhary, SK Yang, K Hudgens, MG Pastan, I Haase, AT Kashuba, AD Berger, EA Margolis, DM Garcia, JV AF Denton, Paul W. Long, Julie M. Wietgrefe, Stephen W. Sykes, Craig Spagnuolo, Rae Ann Snyder, Olivia D. Perkey, Katherine Archin, Nancie M. Choudhary, Shailesh K. Yang, Kuo Hudgens, Michael G. Pastan, Ira Haase, Ashley T. Kashuba, Angela D. Berger, Edward A. Margolis, David M. Garcia, J. Victor TI Targeted Cytotoxic Therapy Kills Persisting HIV Infected Cells During ART SO PLOS PATHOGENS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMANIZED BLT MICE; RICIN-A-CHAIN; EXOTOXIN HYBRID PROTEIN; T-CELLS; ANTIRETROVIRAL THERAPY; IN-VITRO; ENVELOPE GLYCOPROTEIN; IMMUNE-RESPONSES; IMMUNOTOXINS AB Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA) levels throughout the body is important for the development of strategies to eradicate infectious HIV from patients. Essential to a successful eradication therapy is a component capable of killing persisting HIV infected cells during ART. Therefore, we determined the in vivo efficacy of a targeted cytotoxic therapy to kill infected cells that persist despite long-term ART. For this purpose, we first characterized the impact of ART on HIV RNA levels in multiple organs of bone marrow-liver-thymus (BLT) humanized mice and found that antiretroviral drug penetration and activity was sufficient to reduce, but not eliminate, HIV production in each tissue tested. For targeted cytotoxic killing of these persistent vRNA(+) cells, we treated BLT mice undergoing ART with an HIV-specific immunotoxin. We found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies. Author Summary Antiretroviral therapy (ART) improves the quality of life for HIV infected individuals. However, ART is currently a lifelong commitment because HIV persists during treatment despite being suppressed below detection. If therapy is stopped, the HIV reappears. A concerted effort is ongoing to develop new eradication therapies to prevent virus rebound, but there are challenges to be overcome. Our work is a major step forward in this process. We measured persistent HIV throughout the body during ART using bone marrow/liver/thymus (BLT) humanized mice, a model validated to study HIV persistence. HIV infected BLT mice were treated with tenofovir, emtricitabine and raltegravir. Despite documented tissue penetration by these drugs, we found that HIV expression persists in cells isolated from all the tissues analyzed (bone marrow, thymus, spleen, lymph nodes, liver, lung, intestines and peripheral blood cells). We therefore complemented ART with an immunotoxin that specifically kills HIV expressing cells while leaving other cells untouched. Our results demonstrate a dramatic reduction in persistent HIV throughout the body resulting from the killing of virus producing cells. Thus, our study provides new insights into the locations of HIV persistence during ART and a demonstration that persistent HIV can be successfully targeted inside the body. C1 [Denton, Paul W.; Long, Julie M.; Spagnuolo, Rae Ann; Snyder, Olivia D.; Archin, Nancie M.; Choudhary, Shailesh K.; Margolis, David M.; Garcia, J. Victor] Univ N Carolina, Sch Med, Dept Med, Div Infect Dis,UNC Ctr AIDS Res, Chapel Hill, NC 27514 USA. [Wietgrefe, Stephen W.; Perkey, Katherine; Haase, Ashley T.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. [Sykes, Craig; Yang, Kuo; Kashuba, Angela D.] Univ N Carolina, Sch Med, UNC Ctr AIDS Res, Div Pharmacotherapy & Expt Therapeut,UNC Eshelman, Chapel Hill, NC USA. [Hudgens, Michael G.] Univ N Carolina, Sch Med, Dept Biostat, UNC Ctr AIDS Res, Chapel Hill, NC USA. [Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Berger, Edward A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Garcia, JV (reprint author), Univ N Carolina, Sch Med, Dept Med, Div Infect Dis,UNC Ctr AIDS Res, Chapel Hill, NC 27514 USA. EM victor_garcia@med.unc.edu OI Denton, Paul/0000-0003-2458-8147; Margolis, David/0000-0001-5714-0002 FU National Institutes of Health [AI096113]; UNC Center for AIDS Research [P30 AI50410]; Intramural Program of the NIH, NIAID; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This work was supported in part by: National Institutes of Health grants AI096113 (JVG), and the UNC Center for AIDS Research Grant P30 AI50410, as well as by the Intramural Program of the NIH, NIAID and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. NR 59 TC 48 Z9 48 U1 1 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2014 VL 10 IS 1 AR e1003872 DI 10.1371/journal.ppat.1003872 PG 9 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AC6NQ UT WOS:000332640900036 PM 24415939 ER PT J AU Sereti, I Estes, JD Thompson, WL Morcock, DR Fischl, MA Croughs, T Beq, S de Micheaux, SL Yao, MD Ober, A Wilson, EMP Natarajan, V Imamichi, H Boulassel, MR Lederman, MM Routy, JP AF Sereti, Irini Estes, Jacob D. Thompson, William L. Morcock, David R. Fischl, Margaret A. Croughs, Therese Beq, Stephanie de Micheaux, Sylvie Lafaye Yao, Michael D. Ober, Alexander Wilson, Eleanor M. P. Natarajan, Ven Imamichi, Hiromi Boulassel, Mohamed R. Lederman, Michael M. Routy, Jean-Pierre TI Decreases in Colonic and Systemic Inflammation in Chronic HIV Infection after IL-7 Administration SO PLOS PATHOGENS LA English DT Article ID MUCOSAL IMMUNE RECONSTITUTION; VIRUS TYPE-1 INFECTION; CD4(+) T-CELLS; ANTIRETROVIRAL THERAPY; LYMPHOID-TISSUE; PLASMA-LEVELS; ACTIVATION; RESTORATION; EXPANSION; RECEPTOR AB Despite antiretroviral therapy (ART), some HIV-infected persons maintain lower than normal CD4(+) T-cell counts in peripheral blood and in the gut mucosa. This incomplete immune restoration is associated with higher levels of immune activation manifested by high systemic levels of biomarkers, including sCD14 and D-dimer, that are independent predictors of morbidity and mortality in HIV infection. In this 12-week, single-arm, open-label study, we tested the efficacy of IL-7 adjunctive therapy on T-cell reconstitution in peripheral blood and gut mucosa in 23 ART suppressed HIV-infected patients with incomplete CD4(+) T-cell recovery, using one cycle (consisting of three subcutaneous injections) of recombinant human IL-7 (r-hIL-7) at 20 mu g/kg. IL-7 administration led to increases of both CD4(+) and CD8(+) T-cells in peripheral blood, and importantly an expansion of T-cells expressing the gut homing integrin 47. Participants who underwent rectosigmoid biopsies at study baseline and after treatment had T-cell increases in the gut mucosa measured by both flow cytometry and immunohistochemistry. IL-7 therapy also resulted in apparent improvement in gut barrier integrity as measured by decreased neutrophil infiltration in the rectosigmoid lamina propria 12 weeks after IL-7 administration. This was also accompanied by decreased TNF and increased FOXP3 expression in the lamina propria. Plasma levels of sCD14 and D-dimer, indicative of systemic inflammation, decreased after r-hIL-7. Increases of colonic mucosal T-cells correlated strongly with the decreased systemic levels of sCD14, the LPS coreceptor - a marker of monocyte activation. Furthermore, the proportion of inflammatory monocytes expressing CCR2 was decreased, as was the basal IL-1 production of peripheral blood monocytes. These data suggest that administration of r-hIL-7 improves the gut mucosal abnormalities of chronic HIV infection and attenuates the systemic inflammatory and coagulation abnormalities that have been linked to it. Author Summary HIV infected people who receive antiretroviral therapy (ART) remain at higher risk of non-infectious complications such as cardiovascular disease. This risk is linked to persistent inflammation and immune activation and is higher in those with lower circulating CD4(+) T-cell counts. IL-7 therapy can increase CD4(+) and CD8(+) T-cell counts in peripheral blood, but its effects on gut mucosal T cell restoration was unknown. We gave 3 doses of interleukin (IL)-7 to HIV+ persons receiving ART and performed gut biopsies before and after therapy. IL-7 therapy increased T-cell numbers in the periphery including T-cells that express the 47 integrin, a molecule that promotes trafficking to the gut. Gut mucosa studies showed significant increases of T-cells and significant decreases in local inflammation as reflected by expression of myeloperoxidase and tumor necrosis factor. In addition, plasma levels of inflammatory markers that are linked to mortality in HIV infection decreased significantly as did some inflammatory monocyte markers. We conclude that IL-7 administration can improve gut mucosal abnormalities in chronic treated HIV infection and as a result, also may decrease both gut and systemic inflammation. C1 [Sereti, Irini; Thompson, William L.; Yao, Michael D.; Ober, Alexander; Wilson, Eleanor M. P.; Imamichi, Hiromi] NIAID, NIH, Bethesda, MD 20892 USA. [Estes, Jacob D.; Morcock, David R.; Natarajan, Ven] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. [Fischl, Margaret A.] Univ Miami, Sch Med, Miami, FL USA. [Croughs, Therese; Beq, Stephanie; de Micheaux, Sylvie Lafaye] Cytheris, Paris, France. [Boulassel, Mohamed R.; Routy, Jean-Pierre] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Lederman, Michael M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Sereti, I (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM isereti@niaid.nih.gov OI Wilson, Eleanor/0000-0002-4855-514X FU Intramural Research Program of NIAID; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Canadian Institutes of Health Research [103230]; CIHR CTN/HIV trial Network [CTN 247]; FRQ-S SIDA maladies infectieuses; Cytheris FX This work was supported in part by the Intramural Research Program of NIAID. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. This work was also supported in part by the Canadian Institutes of Health Research grant # 103230, CIHR CTN/HIV trial Network (CTN 247) and FRQ-S SIDA maladies infectieuses. The clinical trial and part of the laboratory work was sponsored by Cytheris. Cytheris employees participated in the manuscript preparation but all data were analyzed by NIH staff. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 42 TC 37 Z9 37 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2014 VL 10 IS 1 AR e1003890 DI 10.1371/journal.ppat.1003890 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AC6NQ UT WOS:000332640900011 PM 24497828 ER PT J AU Bonomi, AE Trabert, B Anderson, ML Kernic, MA Holt, VL AF Bonomi, Amy E. Trabert, Britton Anderson, Melissa L. Kernic, Mary A. Holt, Victoria L. TI Intimate Partner Violence and Neighborhood Income: A Longitudinal Analysis SO VIOLENCE AGAINST WOMEN LA English DT Article DE intimate partner violence; longitudinal; risk factors ID DISPARITIES GEOCODING PROJECT; SOCIAL-DISORGANIZATION THEORY; ALCOHOL-RELATED PROBLEMS; DOMESTIC VIOLENCE; HISPANIC COUPLES; SOCIOECONOMIC INEQUALITIES; COLLECTIVE EFFICACY; CONTEXTUAL ANALYSIS; DRINKING PATTERNS; WOMEN AB This investigation used a longitudinal design to examine the relationship between neighborhood-level income, individual-level predictors, and police-reported intimate partner violence in 5,994 urban couples followed over 2 years. At the baseline abuse incident, intimate partner violence rates were highest in the poorest neighborhoods (13.8 per 1,000 women in the lowest income quartile, followed by 12.1, 8.2, and 5.0 in the respective higher income quartiles). However, in the longitudinal analysis, weapon use at the baseline abuse event was a much stronger predictor of repeat abuse (incident rate ratios ranging from 1.72 for physical abuse to 1.83 for non-physical abuse) than neighborhood income. C1 [Bonomi, Amy E.] Michigan State Univ, Dept Human Dev & Family Studies, E Lansing, MI 48824 USA. [Trabert, Britton] NCI, Hormonal & Reprod Epidemiol Branch, Rockville, MD USA. [Anderson, Melissa L.] Grp Hlth Res Inst, Seattle, WA USA. [Kernic, Mary A.; Holt, Victoria L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Bonomi, AE (reprint author), Michigan State Univ, 552 W Circle Dr, E Lansing, MI 48824 USA. EM bonomi@msu.edu RI Trabert, Britton/F-8051-2015 FU NCIPC CDC HHS [R-49 CE000670-01] NR 64 TC 5 Z9 5 U1 8 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-8012 EI 1552-8448 J9 VIOLENCE AGAINST WOM JI Violence Against Women PD JAN PY 2014 VL 20 IS 1 BP 42 EP 58 DI 10.1177/1077801213520580 PG 17 WC Women's Studies SC Women's Studies GA AB3KS UT WOS:000331690300004 PM 24476760 ER PT S AU Tusting, LS Bousema, T Smith, DL Drakeley, C AF Tusting, Lucy S. Bousema, Teun Smith, David L. Drakeley, Chris BE Rollinson, D TI Measuring Changes in Plasmodium falciparum Transmission: Precision, Accuracy and Costs of Metrics SO ADVANCES IN PARASITOLOGY, VOL 84 SE Advances in Parasitology LA English DT Review; Book Chapter ID ENTOMOLOGICAL INOCULATION RATE; PAPUA-NEW-GUINEA; VECTOR INFECTION-RATES; MALARIA TRANSMISSION; ANOPHELES-GAMBIAE; CIRCUMSPOROZOITE PROTEIN; HUMAN-POPULATIONS; POSITIVITY RATES; NORTHERN GHANA; WESTERN KENYA AB As malaria declines in parts of Africa and elsewhere, and as more countries move towards elimination, it is necessary to robustly evaluate the effect of interventions and control programmes on malaria transmission. To help guide the appropriate design of trials to evaluate transmission-reducing interventions, we review 11 metrics of malaria transmission, discussing their accuracy, precision, collection methods and costs and presenting an overall critique. We also review the nonlinear scaling relationships between five metrics of malaria transmission: the entomological inoculation rate, force of infection, sporozoite rate, parasite rate and the basic reproductive number, R-0. Our chapter highlights that while the entomological inoculation rate is widely considered the gold standard metric of malaria transmission and may be necessary for measuring changes in transmission in highly endemic areas, it has limited precision and accuracy and more standardised methods for its collection are required. In areas of low transmission, parasite rate, seroconversion rates and molecular metrics including MOI and mFOI may be most appropriate. When assessing a specific intervention, the most relevant effects will be detected by examining the metrics most directly affected by that intervention. Future work should aim to better quantify the precision and accuracy of malaria metrics and to improve methods for their collection. C1 [Tusting, Lucy S.] London Sch Hyg & Trop Med, Dept Dis Control, London WC1, England. [Bousema, Teun; Drakeley, Chris] London Sch Hyg & Trop Med, Dept Infect & Immun, London WC1, England. [Bousema, Teun] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, NL-6525 ED Nijmegen, Netherlands. [Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, Baltimore, MD USA. [Smith, David L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Smith, DL (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. EM dlsmith@jhsph.edu RI Bousema, Teun/N-3574-2014; Smith, David/L-8850-2013; OI Smith, David/0000-0003-4367-3849; Tusting, Lucy/0000-0002-6897-8625 FU FIC NIH HHS [K01 TW000007]; Wellcome Trust [091924] NR 146 TC 31 Z9 31 U1 3 U2 14 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-308X BN 978-0-12-800099-1 J9 ADV PARASIT JI Adv.Parasitol. PY 2014 VL 84 BP 151 EP 208 DI 10.1016/B978-0-12-800099-1.00003-X PG 58 WC Parasitology SC Parasitology GA BA2GQ UT WOS:000333377500003 PM 24480314 ER PT J AU Epstein, DH Tyburski, M Craig, IM Phillips, KA Jobes, ML Vahabzadeh, M Mezghanni, M Lin, JL Furr-Holden, CDM Preston, KL AF Epstein, David H. Tyburski, Matthew Craig, Ian M. Phillips, Karran A. Jobes, Michelle L. Vahabzadeh, Massoud Mezghanni, Mustapha Lin, Jia-Ling Furr-Holden, C. Debra M. Preston, Kenzie L. TI Real-time tracking of neighborhood surroundings and mood in urban drug misusers: Application of a new method to study behavior in its geographical context SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Behavioral geography; Activity space; Ecological momentary assessment ID ECOLOGICAL MOMENTARY ASSESSMENT; HEALTH; INEQUALITIES; DEPRIVATION; ADDICTION; EXPOSURES; CESSATION; DISORDER; SMOKING; OBESITY AB Background: Maladaptive behaviors may be more fully understood and efficiently prevented by ambulatory tools that assess people's ongoing experience in the context of their environment. Methods: To demonstrate new field-deployable methods for assessing mood and behavior as a function of neighborhood surroundings (geographical momentary assessment; GMA), we collected time-stamped GPS data and ecological momentary assessment (EMA) ratings of mood, stress, and drug craving over 16 weeks at randomly prompted times during the waking hours of opioid-dependent polydrug users receiving methadone maintenance. Locations of EMA entries and participants' travel tracks calculated for the 12 before each EMA entry were mapped. Associations between subjective ratings and objective environmental ratings were evaluated at the whole neighborhood and 12-h track levels. Results: Participants (N=27) were compliant with GMA data collection; 3711 randomly prompted EMA entries were matched to specific locations. At the neighborhood level, physical disorder was negatively correlated with negative mood, stress, and heroin and cocaine craving (ps < .0001-.0335); drug activity was negatively correlated with stress, heroin and cocaine craving (ps.0009-.0134). Similar relationships were found for the environments around respondents' tracks in the 12 h preceding EMA entries. Conclusions: The results support the feasibility of GMA. The relationships between neighborhood characteristics and participants' reports were counterintuitive and counter-hypothesized, and challenge some assumptions about how ostensibly stressful environments are associated with lived experience and how such environments ultimately impair health. GMA methodology may have applications for development of individual- or neighborhood-level interventions. Published by Elsevier Ireland Ltd. C1 [Epstein, David H.; Tyburski, Matthew; Craig, Ian M.; Phillips, Karran A.; Jobes, Michelle L.; Preston, Kenzie L.] NIDA, Treatment Sect, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. [Vahabzadeh, Massoud; Lin, Jia-Ling] NIDA, Biomed Informat Sect, Adm Management Branch, Intramural Res Program, Baltimore, MD 21224 USA. [Mezghanni, Mustapha] NIDA, Johns Hopkins Bayview Med Ctr, Baltimore, MD 21224 USA. [Furr-Holden, C. Debra M.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21202 USA. RP Preston, KL (reprint author), NIDA, Treatment Sect, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM kpreston@intra.nida.nih.gov FU Intramural Research Program (IRP) of the National Institute on Drug Abuse (NIDA) FX This research was supported by the Intramural Research Program (IRP) of the National Institute on Drug Abuse (NIDA). The authors had sole responsibility for the design and conduct of the study, the analysis and interpretation of the data, and the preparation and review of the manuscript. NR 34 TC 26 Z9 26 U1 3 U2 19 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2014 VL 134 BP 22 EP 29 DI 10.1016/j.drugalcdep.2013.09.007 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AC3MI UT WOS:000332425500003 PM 24332365 ER PT J AU Keyes, KM Shmulewitz, D Greenstein, E McLaughlin, K Wall, M Aharonovich, E Weizman, A Frisch, A Spivak, B Grant, BF Hasin, D AF Keyes, Katherine M. Shmulewitz, Dvora Greenstein, Eliana McLaughlin, Kate Wall, Melanie Aharonovich, Efrat Weizman, Abraham Frisch, Amos Spivak, Baruch Grant, Bridget F. Hasin, Deborah TI Exposure to the Lebanon War of 2006 and effects on alcohol use disorders: The moderating role of childhood maltreatment SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcohol disorders; War; Stress; Childhood maltreatment; Israel; Interaction ID POSTTRAUMATIC-STRESS-DISORDER; INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; MENTAL-HEALTH OUTCOMES; COMMUNITY-BASED SAMPLE; LIFE EVENTS; SUBSTANCE-ABUSE; DRUG MODULES; PSYCHIATRIC-DISORDERS; NICOTINE DEPENDENCE AB Background: Civilian populations now comprise the majority of casualties in modern warfare, but effects of war exposure on alcohol disorders in the general population are largely unexplored. Accumulating literature indicates that adverse experiences early in life sensitize individuals to increased alcohol problems after adult stressful experiences. However, child and adult stressful experiences can be correlated, limiting interpretation. We examine risk for alcohol disorders among Israelis after the 2006 Lebanon War, a fateful event outside the control of civilian individuals and uncorrelated with childhood experiences. Further, we test whether those with a history of maltreatment are at greater risk for an alcohol use disorder after war exposure compared to those without such a history. Methods: Adult household residents selected from the Israeli population register were assessed with a psychiatric structured interview; the analyzed sample included 1306 respondents. War measures included self-reported days in an exposed region. Results: Among those with a history of maltreatment, those in a war-exposed region for 30+ days had 5.3 times the odds of subsequent alcohol disorders compared to those exposed 0 days (95%C.I. 1.01-27.76), controlled for relevant confounders; the odds ratio for those without this history was 0.5 (95%C.I. 0.25-1.01); test for interaction: X-2 = 5.28, df = 1, P = 0.02. Conclusions: Experiencing a fateful stressor outside the control of study participants, civilian exposure to the 2006 Lebanon War, is associated with a heightened the risk of alcohol disorders among those with early adverse childhood experiences. Results suggest that early life experiences may sensitize individuals to adverse health responses later in life. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Keyes, Katherine M.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Shmulewitz, Dvora; Greenstein, Eliana; Aharonovich, Efrat; Hasin, Deborah] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Shmulewitz, Dvora; Greenstein, Eliana; Aharonovich, Efrat; Hasin, Deborah] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY 10032 USA. [McLaughlin, Kate] Harvard Univ, Sch Med, Div Gen Pediat, Childrens Hosp Boston, Boston, MA 02115 USA. [Wall, Melanie] Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Weizman, Abraham; Frisch, Amos; Spivak, Baruch] Tel Aviv Univ, Sackler Fac Med, Felsenstein Med Res Ctr, IL-69978 Tel Aviv, Israel. [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. RP Keyes, KM (reprint author), Columbia Univ, Dept Epidemiol, 722 West 168th St,Suite 503, New York, NY 10032 USA. EM kmk2104@columbia.edu OI McLaughlin, Katie/0000-0002-1362-2410 FU National Institutes of Health [R01AA013654, U01AA018111, K05AA014223]; Department of Epidemiology at the Mailman School of Public Health; New York State Psychiatric Institute FX This work was supported by National Institutes of Health grants [R01AA013654, U01AA018111, K05AA014223 to D.H.]; Department of Epidemiology at the Mailman School of Public Health to [K.K]; and the New York State Psychiatric Institute to [M.W., D.H]. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. We acknowledge the advice of Bruce Dohrenwend in creating the narrative method of war exposure in this study, and the helpful consultations of Dr. Rachel Bar-Hamburger in collecting the data in Israel. The authors have no conflicts of interest to report. NR 70 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2014 VL 134 BP 296 EP 303 DI 10.1016/j.drugalcdep.2013.10.014 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AC3MI UT WOS:000332425500040 PM 24262650 ER PT J AU Le Couteur, DG Wilder, SM de Cabo, R Simpson, SJ AF Le Couteur, David G. Wilder, Shawn M. de Cabo, Rafael Simpson, Stephen J. TI The Evolution of Research on Ageing and Nutrition SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID CALORIC RESTRICTION; LIFE-SPAN; RHESUS-MONKEYS; HEALTH C1 [Le Couteur, David G.] Univ Sydney, Ctr Educ & Res Ageing, Sydney, NSW 2139, Australia. [Le Couteur, David G.] Concord RG Hosp, Sydney, NSW 2139, Australia. [Le Couteur, David G.; Wilder, Shawn M.; Simpson, Stephen J.] Univ Sydney, Charles Perkins Ctr, Sydney, NSW 2139, Australia. [Le Couteur, David G.] Univ Sydney, ANZAC Res Inst, Sydney, NSW 2139, Australia. [Wilder, Shawn M.; Simpson, Stephen J.] Univ Sydney, Sch Biol Sci, Sydney, NSW 2139, Australia. [de Cabo, Rafael] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. RP Le Couteur, DG (reprint author), Univ Sydney, Ctr Educ & Res Ageing, Sydney, NSW 2139, Australia. EM david.lecouteur@sydney.edu.au RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; Simpson, Stephen J./0000-0003-0256-7687; , rafael/0000-0003-2830-5693 NR 15 TC 5 Z9 5 U1 3 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2014 VL 69 IS 1 BP 1 EP 2 DI 10.1093/gerona/glt130 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6PY UT WOS:000333384500001 PM 24022588 ER PT J AU Tseng, LA Delmonico, MJ Visser, M Boudreau, RM Goodpaster, BH Schwartz, AV Simonsick, EM Satterfield, S Harris, T Newman, AB AF Tseng, Lisa A. Delmonico, Matthew J. Visser, Marjolein Boudreau, Robert M. Goodpaster, Bret H. Schwartz, Ann V. Simonsick, Eleanor M. Satterfield, Suzanne Harris, Tamara Newman, Anne B. TI Body Composition Explains Sex Differential in Physical Performance Among Older Adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Body composition; Physical performance; Epidemiology ID LEG MUSCLE MASS; SKELETAL-MUSCLE; COMPUTED-TOMOGRAPHY; HEALTH ABC; DISABILITY; WOMEN; MEN; MOBILITY; STRENGTH; FAT AB Background. Older women have higher percent body fat, poorer physical function, lower strength, and higher rates of nonfatal chronic conditions than men. We sought to determine whether these differences explained physical performance differences between men and women. Methods. Physical performance was assessed in the Health, Aging and Body Composition study in 2,863 men and women aged 70-79 with a composite 0-4 point score consisting of chair stands, standing balance including one-leg stand, and 6-m usual and narrow walk tests. Total body composition was measured by dual x-ray absorptiometry, thigh composition by computed tomography, and knee extensor strength by isokinetic dynamometer. Analysis of covariance estimated least square mean performance scores for men and women. Results. Men had higher performance scores than women (least square means: 2.33 +/- 0.02 vs 2.03 +/- 0.02, p < .0001), adjusted for race, study site, age, and height. Body composition measures (total body fat and thigh muscle area, muscle density, subcutaneous fat, and intermuscular fat) accounted for differences between men and women (least square means: 2.15 +/- 0.02 vs 2.17 +/- 0.02, p = .53). Higher strength in men partly explained the sex difference (least square means: 2.28 +/- 0.02 vs 2.12 +/- 0.02, p < .0001). Strength attenuated the association of thigh muscle mass with performance. Chronic health conditions did not explain the sex difference. Conclusions. In a well-functioning cohort, poorer physical function in women compared with men can be explained predominantly by their higher fat mass, but also by other body composition differences. The higher proportion of body fat in women may put them at significant biomechanical disadvantage for greater disability in old age. C1 [Tseng, Lisa A.] Univ Pittsburgh, Sch Med, Clin Scientist Training Program, Pittsburgh, PA 15260 USA. [Tseng, Lisa A.; Boudreau, Robert M.; Newman, Anne B.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Delmonico, Matthew J.] Univ Rhode Isl, Dept Kinesiol, Kingston, RI 02881 USA. [Visser, Marjolein] Vrije Univ Amsterdam, Dept Hlth Sci, Amsterdam, Netherlands. [Visser, Marjolein] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. [Goodpaster, Bret H.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Simonsick, Eleanor M.; Harris, Tamara] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. RP Tseng, LA (reprint author), 130 North Bellefield Ave,Suite 500, Pittsburgh, PA 15213 USA. EM lisa.ajt@gmail.com RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187 FU Doris Duke Charitable Foundation via the University of Pittsburgh School of Medicine; Pittsburgh Training in Geriatrics and Gerontolog [T32 AG021885]; National Institutes of Health, National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; National Institutes of Health, National Institute on Aging (NIA) (NINR) [R01-NR012459] FX This work was supported by the Clinical Research Fellowship from the Doris Duke Charitable Foundation via the University of Pittsburgh School of Medicine and by the Pittsburgh Training in Geriatrics and Gerontology (T32 AG021885 to L. A. T.). This study was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging (NIA) Contracts (N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106; NIA grant R01-AG028050; and NINR grant R01-NR012459). NR 20 TC 16 Z9 16 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2014 VL 69 IS 1 BP 93 EP 100 DI 10.1093/gerona/glt027 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6PY UT WOS:000333384500012 PM 23682159 ER PT J AU Murphy, RA Register, TC Shively, CA Carr, JJ Ge, YR Heilbrun, ME Cummings, SR Koster, A Nevitt, MC Satterfield, S Tylvasky, FA Strotmeyer, ES Newman, AB Simonsick, EM Scherzinger, A Goodpaster, BH Launer, LJ Eiriksdottir, G Sigurdsson, S Sigurdsson, G Gudnason, V Lang, TF Kritchevsky, SB Harris, TB AF Murphy, Rachel A. Register, Thomas C. Shively, Carol A. Carr, J. Jeffrey Ge, Yaorong Heilbrun, Marta E. Cummings, Steven R. Koster, Annemarie Nevitt, Michael C. Satterfield, Suzanne Tylvasky, Frances A. Strotmeyer, Elsa S. Newman, Anne B. Simonsick, Eleanor M. Scherzinger, Ann Goodpaster, Bret H. Launer, Lenore J. Eiriksdottir, Gudny Sigurdsson, Sigurdur Sigurdsson, Gunnar Gudnason, Vilmundur Lang, Thomas F. Kritchevsky, Stephen B. Harris, Tamara B. TI Adipose Tissue Density, a Novel Biomarker Predicting Mortality Risk in Older Adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Obesity; Aging; Leptin; Adiponectin ID ALL-CAUSE MORTALITY; BODY-MASS INDEX; FEMALE CYNOMOLGUS MONKEYS; CHRONIC HEART-FAILURE; WEIGHT-LOSS; DIABETES-MELLITUS; VISCERAL FAT; ADIPONECTIN; HEALTH; DISEASE AB Background. Knowledge of adipose composition in relation to mortality may help delineate inconsistent relationships between obesity and mortality in old age. We evaluated relationships between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density, mortality, biomarkers, and characteristics. Methods. VAT and SAT density were determined from computed tomography scans in persons aged 65 and older, Health ABC (n = 2,735) and AGES-Reykjavik (n = 5,131), and 24 nonhuman primates (NHPs). Associations between adipose density and mortality (4-13 years follow-up) were assessed with Cox proportional hazards models. In NHPs, adipose density was related to serum markers and tissue characteristics. Results. Higher density adipose tissue was associated with mortality in both studies with adjustment for risk factors including adipose area, total fat, and body mass index. In women, hazard ratio and 95% CI for the densest quintile (Q5) versus least dense (Q1) for VAT density were 1.95 (1.36-2.80; Health ABC) and 1.88 (1.31-2.69; AGES-Reykjavik) and for SAT density, 1.76 (1.35-2.28; Health ABC) and 1.56 (1.15-2.11; AGES-Reykjavik). In men, VAT density was associated with mortality in Health ABC, 1.52 (1.12-2.08), whereas SAT density was associated with mortality in both Health ABC, 1.58 (1.21-2.07), and AGES-Reykjavik, 1.43 (1.07-1.91). Higher density adipose tissue was associated with smaller adipocytes in NHPs. There were no consistent associations with inflammation in any group. Higher density adipose tissue was associated with lower serum leptin in Health ABC and NHPs, lower leptin mRNA expression in NHPs, and higher serum adiponectin in Health ABC and NHPs. Conclusion. VAT and SAT density provide a unique marker of mortality risk that does not appear to be inflammation related. C1 [Murphy, Rachel A.; Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Populat Sci, Intramural Res Program, Bethesda, MD 20814 USA. [Register, Thomas C.] Wake Forest Sch Med, Sticht Ctr Aging, Sect Comparat Med Pathol, Winston Salem, NC USA. [Shively, Carol A.] Wake Forest Sch Med, Sect Comparat Med Pathol, Winston Salem, NC USA. [Carr, J. Jeffrey] Wake Forest Sch Med, Sect Radiol Sci, Winston Salem, NC USA. [Ge, Yaorong] Wake Forest Sch Med, Dept Biomed Engn, Winston Salem, NC USA. [Heilbrun, Marta E.] Univ Utah, Dept Radiol, Salt Lake City, UT 84132 USA. [Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Koster, Annemarie] Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care, Maastricht, Netherlands. [Nevitt, Michael C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Satterfield, Suzanne; Tylvasky, Frances A.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Strotmeyer, Elsa S.; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15260 USA. [Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Scherzinger, Ann] Univ Colorado, Dept Radiol, Aurora, CO USA. [Goodpaster, Bret H.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Eiriksdottir, Gudny; Sigurdsson, Sigurdur; Sigurdsson, Gunnar; Gudnason, Vilmundur] Iceland Heart Assoc Res Inst, Kopavogur, Iceland. [Sigurdsson, Gunnar; Gudnason, Vilmundur] Univ Iceland, Dept Med, Reykjavik, Iceland. [Lang, Thomas F.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Kritchevsky, Stephen B.] Wake Forest Sch Med, Sect Gerontol & Geriatr, Winston Salem, NC USA. RP Murphy, RA (reprint author), NIA, Lab Populat Sci, 7201 Wisconsin Ave,3C-309, Bethesda, MD 20814 USA. EM rachel.murphy@nih.gov RI Strotmeyer, Elsa/F-3015-2014; Koster, Annemarie/E-7438-2010; Gudnason, Vilmundur/K-6885-2015; Carr, John/A-1938-2012; Newman, Anne B./C-6408-2013; OI Gudnason, Vilmundur/0000-0001-5696-0084; Carr, John/0000-0002-4398-8237; Newman, Anne B./0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036; Lang, Thomas/0000-0002-3720-8038 FU National Institutes of Health [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG28050, R01-AG28641, R01-HL39789, R01-NR-12459]; Pepper Older Americans for Independence Center [P30 AG21332]; National Institutes of Health, National Institute on Aging; Banting Postdoctoral Fellowship FX This work was supported by National Institutes of Health (N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106; R01-AG28050, R01-AG28641, R01-HL39789, R01-NR-12459) and the Pepper Older Americans for Independence Center (P30 AG21332). This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. R. A. M. is supported by a Banting Postdoctoral Fellowship. NR 29 TC 16 Z9 16 U1 2 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2014 VL 69 IS 1 BP 109 EP 117 DI 10.1093/gerona/glt070 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6PY UT WOS:000333384500014 PM 23707956 ER PT J AU Albuquerque, P Nicola, AM Nieves, E Paes, HC Williamson, PR Silva-Pereira, I Casadevall, A AF Albuquerque, Patricia Nicola, Andre M. Nieves, Edward Paes, Hugo Costa Williamson, Peter R. Silva-Pereira, Ildinete Casadevall, Arturo TI Quorum Sensing-Mediated, Cell Density-Dependent Regulation of Growth and Virulence in Cryptococcus neoformans SO MBIO LA English DT Article ID CANDIDA-ALBICANS; FUNGI; FARNESOL; ANTIBODY; TYROSOL; TALK AB Quorum sensing (QS) is a cell density-dependent mechanism of communication between microorganisms, characterized by the release of signaling molecules that affect microbial metabolism and gene expression in a synchronized way. In this study, we investigated cell density-dependent behaviors mediated by conditioned medium (CM) in the pathogenic encapsulated fungus Cryptococcus neoformans. CM produced dose-dependent increases in the growth of planktonic and biofilm cells, glucuronoxylomannan release, and melanin synthesis, important virulence attributes of this organism. Mass spectrometry revealed the presence of pantothenic acid (PA) in our samples, and commercial PA was able to increase growth and melanization, although not to the same extent as CM. Additionally, we found four mutants that were either unable to produce active CM or failed to respond with increased growth in the presence of wild-type CM, providing genetic evidence for the existence of intercellular communication in C. neoformans. C. neoformans CM also increased the growth of Cryptococcus albidus, Candida albicans, and Saccharomyces cerevisiae. Conversely, CM from Cryptococcus albidus, C. albicans, S. cerevisiae, and Sporothrix schenckii increased C. neoformans growth. In summary, we report the existence of a new QS system regulating the growth and virulence factor expression of C. neoformans in vitro and, possibly, also able to regulate growth in other fungi. IMPORTANCE Quorum sensing is a strategy of communication used by pathogenic microorganisms to coordinate the expression of attributes necessary to cause disease. In this work, we describe a quorum sensing system in Cryptococcus neoformans, a yeast that can cause severe central nervous system infections. Adding conditioned medium-culture medium in which C. neoformans has previously grown-to fresh cultures resulted in faster growth of C. neoformans both as isolated cells and in microbial communities called biofilms. The addition of conditioned medium also increased the secretion of capsule carbohydrates and the formation of melanin pigment, two tools used by this microorganism to thrive in the host. This remarkable example of microbial communication shows that C. neoformans cells can act in unison when expressing attributes necessary to survive in the host, a finding that could point the way to improvements in the treatment of cryptococcosis. C1 [Albuquerque, Patricia; Nicola, Andre M.; Casadevall, Arturo] Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. [Albuquerque, Patricia; Paes, Hugo Costa; Silva-Pereira, Ildinete] Univ Brasilia, Dept Cell Biol, Mol Biol Lab, BR-70910900 Brasilia, DF, Brazil. [Albuquerque, Patricia; Nicola, Andre M.] Univ Catolica Brasilia, Grad Program Genom Sci & Biotechnol, Brasilia, DF, Brazil. [Nieves, Edward] Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. [Nieves, Edward] Yeshiva Univ Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA. [Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Williamson, Peter R.] Univ Illinois, Dept Med, Sect Infect Dis Immunol & Int Med, Chicago, IL USA. [Casadevall, Arturo] Yeshiva Univ Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. RP Albuquerque, P (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM patricia.andrade@phd.einstein.yu.edu RI Albuquerque, Patricia/H-1403-2011; Silva-Pereira, Ildinete/C-7509-2011 OI Silva-Pereira, Ildinete/0000-0003-1403-9363 FU CAPES-Brazil/Fulbright scholarship; NIH [HL059842, AI033774, AI033142, AI052733]; Center for AIDS Research at Albert Einstein College of Medicine; United States Public Health Service [NIH-AI45995, NIH-AI49371]; Intramural Research Program of the NIH, NIAID; NIH SIG [1S10RR019352, 1S10RR019891] FX P.A. was supported by a CAPES-Brazil/Fulbright scholarship. This work was supported by NIH grants HL059842, AI033774, AI033142, and AI052733 and Center for AIDS Research at Albert Einstein College of Medicine. This work was also supported, in part, by United States Public Health Service grants NIH-AI45995 and NIH-AI49371 and by the Intramural Research Program of the NIH, NIAID. The mass spectrometers were purchased using NIH SIG grants 1S10RR019352 (LTQ) and 1S10RR019891 (FT-ICR). NR 33 TC 7 Z9 8 U1 3 U2 25 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2014 VL 5 IS 1 AR e00986-13 DI 10.1128/mBio.00986-13 PG 15 WC Microbiology SC Microbiology GA AC4YF UT WOS:000332526500003 ER PT J AU Arbuckle, JH Kristie, TM AF Arbuckle, Jesse H. Kristie, Thomas M. TI Epigenetic Repression of Herpes Simplex Virus Infection by the Nucleosome Remodeler CHD3 SO MBIO LA English DT Article ID LYTIC INFECTION; GENE-EXPRESSION; CHROMATIN REMODELERS; REGULATORY ELEMENTS; UNSTABLE NUCLEOSOMES; LATENT INFECTION; DNA-REPLICATION; EARLY TIMES; VIRAL-DNA; PROTEIN AB Upon infection, the genome of herpes simplex virus is rapidly incorporated into nucleosomes displaying histone modifications characteristic of heterochromatic structures. The initiation of infection requires complex viral-cellular interactions that ultimately circumvent this repression by utilizing host cell enzymes to remove repressive histone marks and install those that promote viral gene expression. The reversion of repression and activation of viral gene expression is mediated by the cellular coactivator HCF-1 in association with histone demethylases and methyltransferases. However, the mechanisms and the components that are involved in the initial repression remain unclear. In this study, the chromatin remodeler chromodomain helicase DNA binding (CHD3) protein is identified as an important component of the initial repression of the herpesvirus genome. CHD3 localizes to early viral foci and suppresses viral gene expression. Depletion of CHD3 results in enhanced viral immediate early gene expression and an increase in the number of transcriptionally active viral genomes in the cell. Importantly, CHD3 can recognize the repressive histone marks that have been detected in the chromatin associated with the viral genome and this remodeler is important for ultimately reducing the levels of accessible viral genomes. A model is presented in which CHD3 represses viral infection in opposition to the actions of the HCF-1 coactivator complex. This dynamic, at least in part, determines the initiation of viral infection. IMPORTANCE Chromatin modulation of herpesvirus infection is a dynamic process involving regulatory components that mediate suppression and those that promote viral gene expression and the progression of infection. The mechanisms by which the host cell employs the assembly and modulation of chromatin as an antiviral defense strategy against an invading herpesvirus remain unclear. This study defines a critical cellular component that mediates the initial repression of infecting HSV genomes and contributes to understanding the dynamics of this complex interplay between host cell and viral pathogen. C1 [Arbuckle, Jesse H.; Kristie, Thomas M.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Kristie, TM (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM tkristie@niaid.nih.gov FU Laboratory of Viral Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, United States, National Institutes of Health FX These studies were supported by the Laboratory of Viral Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, United States, National Institutes of Health (T.M.K.). NR 52 TC 1 Z9 1 U1 3 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2014 VL 5 IS 1 AR e01027-13 DI 10.1128/mBio.01027-13 PG 7 WC Microbiology SC Microbiology GA AC4YF UT WOS:000332526500005 PM 24425734 ER PT J AU Cotten, M Watson, SJ Zumla, AI Makhdoom, HQ Palser, AL Ong, SH Al Rabeeah, AA Alhakeem, RF Assiri, A Al-Tawfiq, JA Albarrak, A Barry, M Shibl, A Alrabiah, FA Hajjar, S Balkhy, HH Flemban, H Rambaut, A Kellam, P Memish, ZA AF Cotten, Matthew Watson, Simon J. Zumla, Alimuddin I. Makhdoom, Hatem Q. Palser, Anne L. Ong, Swee Hoe Al Rabeeah, Abdullah A. Alhakeem, Rafat F. Assiri, Abdullah Al-Tawfiq, Jaffar A. Albarrak, Ali Barry, Mazin Shibl, Atef Alrabiah, Fahad A. Hajjar, Sami Balkhy, Hanan H. Flemban, Hesham Rambaut, Andrew Kellam, Paul Memish, Ziad A. TI Spread, Circulation, and Evolution of the Middle East Respiratory Syndrome Coronavirus SO MBIO LA English DT Article ID HOST-RANGE EXPANSION; SAUDI-ARABIA; CLINICAL-FEATURES; SARS-CORONAVIRUS; DROMEDARY CAMELS; FUSION CORE; MERS-COV; TRANSMISSION; INFECTION; RECEPTOR AB The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were >= 99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 x 10(-3) substitutions per site per year (95% credible interval [95% CI], 8.76 x 10(-4); 1.37 x 10(-3)) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R-0) for the virus that is less than 1. IMPORTANCE MERS-CoV adaptation toward higher rates of sustained human-to-human transmission appears not to have occurred yet. While MERS-CoV transmission currently appears weak, careful monitoring of changes in MERS-CoV genomes and of the MERS epidemic should be maintained. The observation of phylogenetically related MERS-CoV in geographically diverse locations must be taken into account in efforts to identify the animal source and transmission of the virus. C1 [Cotten, Matthew; Watson, Simon J.; Palser, Anne L.; Ong, Swee Hoe; Kellam, Paul] Wellcome Trust Sanger Inst, Hinxton, England. [Zumla, Alimuddin I.; Al Rabeeah, Abdullah A.; Alhakeem, Rafat F.; Assiri, Abdullah; Memish, Ziad A.] Global Ctr Mass Gatherings Med, Minist Hlth, Riyadh, Saudi Arabia. [Zumla, Alimuddin I.; Kellam, Paul] Univ Coll London Hosp, NHS Fdn Trust, Dept Med Microbiol, London, England. [Zumla, Alimuddin I.; Kellam, Paul] UCL, Div Infect & Immun, London, England. [Makhdoom, Hatem Q.] Minist Hlth, Jeddah Reg Lab, Jeddah, Saudi Arabia. [Al-Tawfiq, Jaffar A.] Saudi Aramco, Saudi Aramco Med Serv Org, Dhahran, Saudi Arabia. [Albarrak, Ali] Prince Sultan Mil Med City, Riyadh, Saudi Arabia. [Barry, Mazin; Shibl, Atef] King Saud Univ, Riyadh, Saudi Arabia. [Alrabiah, Fahad A.; Hajjar, Sami] King Faisal Specialist Hosp & Res Ctr, Riyadh, Saudi Arabia. [Balkhy, Hanan H.] King Abdul Aziz Med City, Riyadh, Saudi Arabia. [Flemban, Hesham] Alhada Mil Hosp, Riyadh, Saudi Arabia. [Rambaut, Andrew] Inst Evolutionary Biol, Ashworth Labs, Edinburgh, Midlothian, Scotland. [Rambaut, Andrew] Fogarty Int Ctr, NIH, Bethesda, MD USA. [Memish, Ziad A.] Alfaisal Univ, Coll Med, Riyadh, Saudi Arabia. RP Memish, ZA (reprint author), Global Ctr Mass Gatherings Med, Minist Hlth, Riyadh, Saudi Arabia. EM zmemish@yahoo.com OI Assiri, Abdullah/0000-0002-5605-2876; Rambaut, Andrew/0000-0003-4337-3707; Zumla, Alimuddin/0000-0002-5111-5735 FU Saudi Arabian Ministry of Health; Wellcome Trust Sanger Institute; European Community [223498, 278433]; National Institute of Health Research Biomedical Research Centre; University College London Hospitals; EDCTP; EC-FW7 FX This work was supported by the Saudi Arabian Ministry of Health, the Wellcome Trust Sanger Institute, and the European Community's Seventh Framework Programme (FP7/2007-2013) under the project EMPE-RIE, European Community grant agreement number 223498, and under the project PREDEMICS, grant agreement number 278433. A.I.Z. acknowledges support from the National Institute of Health Research Biomedical Research Centre, University College London Hospitals, the EDCTP, and the EC-FW7. NR 44 TC 48 Z9 51 U1 3 U2 49 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2014 VL 5 IS 1 AR e01062-13 DI 10.1128/mBio.01062-13 PG 11 WC Microbiology SC Microbiology GA AC4YF UT WOS:000332526500015 ER PT J AU Gorfu, G Cirelli, KM Melo, MB Mayer-Barber, K Crown, D Koller, BH Masters, S Sher, A Leppla, SH Moayeri, M Saeij, JPJ Grigg, ME AF Gorfu, Gezahegn Cirelli, Kimberly M. Melo, Mariane B. Mayer-Barber, Katrin Crown, Devorah Koller, Beverly H. Masters, Seth Sher, Alan Leppla, Stephen H. Moayeri, Mahtab Saeij, Jeroen P. J. Grigg, Michael E. TI Dual Role for Inflammasome Sensors NLRP1 and NLRP3 in Murine Resistance to Toxoplasma gondii SO MBIO LA English DT Article ID GAMMA-INDUCING FACTOR; IFN-GAMMA; INTERFERON-GAMMA; INTRACELLULAR PATHOGENS; HOST-RESISTANCE; ACUTE INFECTION; CUTTING EDGE; NITRIC-OXIDE; CELL-DEATH; ACTIVATION AB Induction of immunity that limits Toxoplasma gondii infection in mice is critically dependent on the activation of the innate immune response. In this study, we investigated the role of cytoplasmic nucleotide-binding domain and leucine-rich repeat containing a pyrin domain (NLRP) inflammasome sensors during acute toxoplasmosis in mice. We show that in vitro Toxoplasma infection of murine bone marrow-derived macrophages activates the NLRP3 inflammasome, resulting in the rapid production and cleavage of interleukin-1 beta (IL-1 beta), with no measurable cleavage of IL-18 and no pyroptosis. Paradoxically, Toxoplasma-infected mice produced large quantities of IL-18 but had no measurable IL-1 beta in their serum. Infection of mice deficient in NLRP3, caspase-1/11, IL-1R, or the inflammasome adaptor protein ASC led to decreased levels of circulating IL-18, increased parasite replication, and death. Interestingly, mice deficient in NLRP1 also displayed increased parasite loads and acute mortality. Using mice deficient in IL-18 and IL-18R, we show that this cytokine plays an important role in limiting parasite replication to promote murine survival. Our findings reveal T. gondii as a novel activator of the NLRP1 and NLRP3 inflammasomes in vivo and establish a role for these sensors in host resistance to toxoplasmosis. IMPORTANCE Inflammasomes are multiprotein complexes that are a major component of the innate immune system. They contain "sensor" proteins that are responsible for detecting various microbial and environmental danger signals and function by activating caspase-1, an enzyme that mediates cleavage and release of the proinflammatory cytokines interleukin-1 beta (IL-1 beta) and IL-18. Toxoplasma gondii is a highly successful protozoan parasite capable of infecting a wide range of host species that have variable levels of resistance. We report here that T. gondii is a novel activator of the NLRP1 and NLRP3 inflammasomes in vivo and establish a role for these sensors in host resistance to toxoplasmosis. Using mice deficient in IL-18 and IL-18R, we show that the IL-18 cytokine plays a pivotal role by limiting parasite replication to promote murine survival. C1 [Gorfu, Gezahegn; Grigg, Michael E.] NIAID, Mol Parasitol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Cirelli, Kimberly M.; Melo, Mariane B.; Saeij, Jeroen P. J.] MIT, Dept Biol, Cambridge, MA USA. [Mayer-Barber, Katrin; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Crown, Devorah; Leppla, Stephen H.; Moayeri, Mahtab] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Koller, Beverly H.] Univ N Carolina, Dept Med, Div Pulm, Chapel Hill, NC USA. [Koller, Beverly H.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Masters, Seth] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. RP Moayeri, M (reprint author), NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mmoayeri@niaid.nih.gov; jsaeij@mit.edu; griggm@niaid.nih.gov RI Melo, Mariane/A-1975-2013; OI Saeij, Jeroen/0000-0003-0289-7109; masters, seth/0000-0003-4763-576X FU Intramural Research Program of the NIH; NIAID; research fellowship award from the Crohn's & Colitis Foundation of America (CCFA); NIH [AI104170]; Pew Scholar in the Biomedical Sciences Award; [R01-AI080621] FX This work was supported in part by the Intramural Research Program of the NIH and NIAID (M. E. G., S. H. L., and A. S.). G. G. was supported by a research fellowship award from the Crohn's & Colitis Foundation of America (CCFA) and is a CCFA Helmsley Scholar. K. M. C. was supported by NIH grant AI104170. J.P.J.S. was supported by R01-AI080621 and a Pew Scholar in the Biomedical Sciences Award. M. E. G. is a scholar of the Canadian Institute for Advanced Research (CIFAR) Program for Integrated Microbial Biodiversity. NR 66 TC 31 Z9 31 U1 1 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2014 VL 5 IS 1 AR e01117-13 DI 10.1128/mBio.01117-13 PG 12 WC Microbiology SC Microbiology GA AC4YF UT WOS:000332526500023 ER PT J AU Laughlin, RC Knodler, LA Barhoumi, R Payne, HR Wu, J Gomez, G Pugh, R Lawhon, SD Baumler, AJ Steele-Mortimer, O Adams, LG AF Laughlin, Richard C. Knodler, Leigh A. Barhoumi, Roula Payne, H. Ross Wu, Jing Gomez, Gabriel Pugh, Roberta Lawhon, Sara D. Baeumler, Andreas J. Steele-Mortimer, Olivia Adams, L. Garry TI Spatial Segregation of Virulence Gene Expression during Acute Enteric Infection with Salmonella enterica serovar Typhimurium SO MBIO LA English DT Article ID III SECRETION SYSTEM; GREEN FLUORESCENT PROTEIN; PATHOGENICITY ISLAND 1; IN-VIVO; MOLECULAR CHARACTERIZATION; EFFECTOR PROTEINS; INTESTINAL-MUCOSA; DENDRITIC CELLS; HOST-CELLS; INVASION AB To establish a replicative niche during its infectious cycle between the intestinal lumen and tissue, the enteric pathogen Salmonella enterica serovar Typhimurium requires numerous virulence genes, including genes for two type III secretion systems (T3SS) and their cognate effectors. To better understand the host-pathogen relationship, including early infection dynamics and induction kinetics of the bacterial virulence program in the context of a natural host, we monitored the subcellular localization and temporal expression of T3SS-1 and T3SS-2 using fluorescent single-cell reporters in a bovine, ligated ileal loop model of infection. We observed that the majority of bacteria at 2 h postinfection are flagellated, express T3SS-1 but not T3SS-2, and are associated with the epithelium or with extruding enterocytes. In epithelial cells, S. Typhimurium cells were surrounded by intact vacuolar membranes or present within membrane-compromised vacuoles that typically contained numerous vesicular structures. By 8 h postinfection, T3SS-2-expressing bacteria were detected in the lamina propria and in the underlying mucosa, while T3SS-1-expressing bacteria were in the lumen. Our work identifies for the first time the temporal and spatial regulation of T3SS-1 and -2 expression during an enteric infection in a natural host and provides further support for the concept of cytosolic S. Typhimurium in extruding epithelium as a mechanism for reseeding the lumen. IMPORTANCE The pathogenic bacterium Salmonella enterica serovar Typhimurium invades and persists within host cells using distinct sets of virulence genes. Genes from Salmonella pathogenicity island 1 (SPI-1) are used to initiate contact and facilitate uptake into nonphagocytic host cells, while genes within SPI-2 allow the pathogen to colonize host cells. While many studies have identified bacterial virulence determinants in animal models of infection, very few have focused on virulence gene expression at the single-cell level during an in vivo infection. To better understand when and where bacterial virulence factors are expressed during an acute enteric infection of a natural host, we infected bovine jejunal-ileal loops with S. Typhimurium cells harboring fluorescent transcriptional reporters for SPI-1 and -2 (PinvF and PssaG, respectively). After a prescribed time of infection, tissue and luminal fluid were collected and analyzed by microscopy. During early infection (<= 2 h), bacteria within both intact and compromised membrane-bound vacuoles were observed within the epithelium, with the majority expressing SPI-1. As the infection progressed, S. Typhimurium displayed differential expression of the SPI-1 and SPI-2 regulons, with the majority of tissue-associated bacteria expressing SPI-2 and the majority of lumen-associated bacteria expressing SPI-1. This underscores the finding that Salmonella virulence gene expression changes as the pathogen transitions from one anatomical location to the next. C1 [Laughlin, Richard C.; Payne, H. Ross; Wu, Jing; Gomez, Gabriel; Pugh, Roberta; Lawhon, Sara D.; Adams, L. Garry] Texas A&M Univ, Dept Vet Pathobiol, Coll Vet Med & Biomed Sci, College Stn, TX 77843 USA. [Knodler, Leigh A.] Washington State Univ, Coll Vet Med, Paul G Allen Sch Global Anim Hlth, Pullman, WA 99164 USA. [Knodler, Leigh A.; Steele-Mortimer, Olivia] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Barhoumi, Roula] Texas A&M Univ, Dept Vet Integrat Biosci, Coll Vet Med & Biomed Sci, College Stn, TX USA. [Baeumler, Andreas J.] Univ Calif Davis, Sch Med, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. RP Adams, LG (reprint author), Texas A&M Univ, Dept Vet Pathobiol, Coll Vet Med & Biomed Sci, College Stn, TX 77843 USA. EM gadams@cvm.tamu.edu RI Lawhon, Sara/G-5147-2011; Baumler, Andreas/H-2301-2011; OI Lawhon, Sara/0000-0001-9154-8909; Baumler, Andreas/0000-0001-9152-7809; Laughlin, Richard/0000-0002-3321-8642 FU National Institute of Allergy and Infectious Diseases [A144170, AI076246]; Paul G. Allen School of Global Animal Health; Intramural Research Program of the National Institutes of Allergy and Infectious Diseases; NIH NCRR Shared Instrumentation grant [1S10RR22532-01]; College of Veterinary Medicine, Texas A&M University, Postdoctoral Trainee Research award FX This work was funded by grants to A.J.B. and L.G.A. from the National Institute of Allergy and Infectious Diseases (A144170 and AI076246). L.A.K. is supported by startup funds from the Paul G. Allen School of Global Animal Health. O.S.-M. is supported by the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases. Confocal and electron microscopy performed at the Image Analysis Laboratory, College of Veterinary Medicine, Texas A&M University, were funded by an NIH NCRR Shared Instrumentation grant (1S10RR22532-01). R.C.L. was partially supported by a College of Veterinary Medicine, Texas A&M University, Postdoctoral Trainee Research award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 7 Z9 7 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2014 VL 5 IS 1 AR e00946-13 DI 10.1128/mBio.00946-13 PG 11 WC Microbiology SC Microbiology GA AC4YF UT WOS:000332526500031 PM 24496791 ER PT J AU Lee, SJ Trostel, A Adhya, S AF Lee, Sang Jun Trostel, Andrei Adhya, Sankar TI Metabolite Changes Signal Genetic Regulatory Mechanisms for Robust Cell Behavior SO MBIO LA English DT Article ID ESCHERICHIA-COLI MUTANTS; GALACTOSE; STRESS; GALACTOSE-1-PHOSPHATE; EXPRESSION; BACTERIA; GROWTH; URIDYLYLTRANSFERASE; ACCUMULATION; SENSITIVITY AB Exploiting mechanisms of utilizing the sugar D-galactose in Escherichia coli as a model system, we explored the consequences of accumulation of critical intermediates of the D-galactose metabolic pathways by monitoring cell growth, metabolites, and transcript profiles. These studies revealed both metabolic network changes far from the D-galactose pathway and changes in the global gene regulatory network. The concentration change of a critical intermediate disturbs the equilibrium state, generating a ripple effect through several metabolic pathways that ends up signaling up- or downregulation of specific sets of genes in a programmed manner to cope with the imbalance. Such long-range effects on metabolites and genetic regulatory mechanisms not only may be a common feature in bacteria but very likely operate during cellular development and differentiation in higher organisms as well as in disease cells, like cancer cells. IMPORTANCE Metabolite accumulation can create adverse intracellular conditions that are relieved by compensatory immediate changes of metabolite pools and later changes of transcript levels. It has been known that gene expression is normally regulated by added catabolic substrates (induction) or anabolic end products (repression). It is becoming apparent now that change in the concentration of metabolic intermediates also plays a critical role in genetic regulatory networks for metabolic homeostasis. Our study provides new insight into how metabolite pool changes transduce signals to global gene regulatory networks. C1 [Lee, Sang Jun] Korea Res Inst Biosci & Biotechnol, Infect & Immun Res Ctr, Taejon, South Korea. [Trostel, Andrei; Adhya, Sankar] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; Basic Science Research Program through the National Research Foundation of Korea; Ministry of Education, Science and Technology [NRF-2012R1A1A2042114]; KRIBB Research Innovative Program, Korea FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and was also supported by the Basic Science Research Program through the National Research Foundation of Korea, funded by the Ministry of Education, Science and Technology (NRF-2012R1A1A2042114), and the KRIBB Research Innovative Program, Korea. NR 40 TC 7 Z9 7 U1 2 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2014 VL 5 IS 1 AR e00972-13 DI 10.1128/mBio.00972-13 PG 8 WC Microbiology SC Microbiology GA AC4YF UT WOS:000332526500033 PM 24473130 ER PT J AU Nussinov, R Wolynes, PG AF Nussinov, Ruth Wolynes, Peter G. TI A second molecular biology revolution? The energy landscapes of biomolecular function SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Editorial Material C1 [Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Wolynes, Peter G.] Rice Univ, Dept Chem, Houston, TX 77005 USA. [Wolynes, Peter G.] Rice Univ, Houston, TX 77005 USA. [Wolynes, Peter G.] Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 USA. RP Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM NussinoR@helix.nih.gov NR 0 TC 15 Z9 15 U1 0 U2 16 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 EI 1463-9084 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2014 VL 16 IS 14 BP 6321 EP 6322 DI 10.1039/c4cp90027h PG 2 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA AD3DZ UT WOS:000333119800001 PM 24608340 ER PT J AU Tsai, CJ Nussinov, R AF Tsai, Chung-Jung Nussinov, Ruth TI The free energy landscape in translational science: how can somatic mutations result in constitutive oncogenic activation? SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID GROWTH-FACTOR RECEPTOR; EGF RECEPTOR; FOLDING FUNNELS; KINASE DOMAIN; CONFORMATIONAL SELECTION; BIOMOLECULAR RECOGNITION; PREEXISTING POPULATIONS; PROTEIN-KINASES; MOLECULAR-BASIS; ALLOSTERY AB The free energy landscape theory has transformed the field of protein folding. The significance of perceiving function in terms of conformational heterogeneity is gradually shifting the interest in the community from folding to function. From the free energy landscape standpoint the principles are unchanged: rather than considering the entire protein conformational landscape, the focus is on the ensemble around the bottom of the folding funnel. The protein can be viewed as populating one of two states: active or inactive. The basins of the two states are separated by a surmountable barrier, which allows the conformations to switch between the states. Unless the protein is a repressor, under physiological conditions it typically populates the inactive state. Ligand binding (or post-translational modification) triggers a switch to the active state. Constitutive allosteric mutations work by shifting the population from the inactive to the active state and keeping it there. This can happen by either destabilizing the inactive state, stabilizing the active state, or both. Identification of the mechanism through which they work is important since it may assist in drug discovery. Here we spotlight the usefulness of the free energy landscape in translational science, illustrating how oncogenic mutations can work in key proteins from the EGFR/Ras/Raf/Erk/Mek pathway, the main signaling pathway in cancer. Finally, we delineate the key components which are needed in order to trace the mechanism of allosteric events. C1 [Tsai, Chung-Jung; Nussinov, Ruth] NCI, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Dept Human Genet & Mol Med, Sackler Inst Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA. EM tsaic@mail.nih.gov; NussinoR@helix.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 83 TC 16 Z9 16 U1 2 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 EI 1463-9084 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2014 VL 16 IS 14 BP 6332 EP 6341 DI 10.1039/c3cp54253j PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA AD3DZ UT WOS:000333119800003 PM 24445437 ER PT J AU Sirur, A Knott, M Best, RB AF Sirur, Anshul Knott, Michael Best, Robert B. TI Effect of interactions with the chaperonin cavity on protein folding and misfolding SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID TRANSITION PATHS; DEPENDENT DIFFUSION; GROEL CAVITY; CONFINEMENT; SIMULATIONS; RATES; THERMODYNAMICS; LANDSCAPE; BINDING; CAGE AB Recent experimental and computational results have suggested that attractive interactions between a chaperonin and an enclosed substrate can have an important effect on the protein folding rate: it appears that folding may even be slower inside the cavity than under unconfined conditions, in contrast to what we would expect from excluded volume effects on the unfolded state. Here we examine systematically the dependence of the protein stability and folding rate on the strength of such attractive interactions between the chaperonin and substrate, by using molecular simulations of model protein systems in an idealised attractive cavity. Interestingly, we find a maximum in stability, and a rate which indeed slows down at high attraction strengths. We have developed a simple phenomenological model which can explain the variations in folding rate and stability due to differing effects on the free energies of the unfolded state, folded state, and transition state; changes in the diffusion coefficient along the folding coordinate are relatively small, at least for our simplified model. In order to investigate a possible role for these attractive interactions in folding, we have studied a recently developed model for misfolding in multidomain proteins. We find that, while encapsulation in repulsive cavities greatly increases the fraction of misfolded protein, sufficiently strong attractive protein-cavity interactions can strongly reduce the fraction of proteins reaching misfolded traps. C1 [Sirur, Anshul; Knott, Michael; Best, Robert B.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England. [Best, Robert B.] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Best, RB (reprint author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England. EM robertbe@helix.nih.gov RI Best, Robert/H-7588-2016 OI Best, Robert/0000-0002-7893-3543 FU BBSRC [BB/H006885/1]; Royal Society at Cambridge; National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health FX AS was supported by a BBSRC doctoral studentship, MK and RBB by BBSRC award BB/H006885/1. RBB was supported by a Royal Society University Research Fellowship while at Cambridge and by the Intramural Research Programme of the National Institute of Diabetes and Digestive and Kidney Diseases while at the National Institutes of Health. NR 55 TC 6 Z9 6 U1 3 U2 15 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 EI 1463-9084 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2014 VL 16 IS 14 BP 6358 EP 6366 DI 10.1039/c3cp52872c PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA AD3DZ UT WOS:000333119800005 PM 24077053 ER PT J AU Malhotra, SV Brown, HC AF Malhotra, Sanjay V. Brown, Herbert C. TI C-2-symmetric N,N'-bis(terpenyl)ethylenediamines-synthesis and application in the enantioselective nitroaldol reaction SO RSC ADVANCES LA English DT Article ID THIOUREA BIFUNCTIONAL ORGANOCATALYST; AMINOPHOSPHINE-RHODIUM COMPLEXES; HENRY REACTION; CHIRAL LIGANDS; 4-SUBSTITUTED CYCLOHEXANONES; ASYMMETRIC HYDROGENATION; CONJUGATE ADDITION; ALDOL REACTIONS; LITHIUM AMIDES; DEPROTONATION AB Optically pure C-2-symmetric chiral diamines, have been synthesized by the reaction of terpenylamines with diethyloxalate, followed by the reduction of diamide with BH3-BF3. The methodology has been successfully applied and high yields achieved in the synthesis of chiral diamines derived from terpenes such as a-pinene, beta-pinene, and 2-iso- and 4-carenes. These chiral diamines are found to be to be highly effective in inducing chirality in the nitroaldol reaction. C1 [Brown, Herbert C.] Purdue Univ, HC Brown & RB Wetherill Labs Chem, W Lafayette, IN 47907 USA. RP Malhotra, SV (reprint author), Biomed Res Inc, Lab Synthet Chem, Leidos, Frederick Natl Lab Canc Res, 1050 Boyles St, Frederick, MD USA. EM malhotrasa@mail.nih.gov FU United States Army Research Office [DAAH-94-G-O3L3] FX Financial support from the United States Army Research Office, Grant no. (DAAH-94-G-O3L3), is gratefully acknowledged. NR 54 TC 4 Z9 4 U1 6 U2 36 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2046-2069 J9 RSC ADV JI RSC Adv. PY 2014 VL 4 IS 27 BP 14264 EP 14269 DI 10.1039/c4ra00193a PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA AD4GD UT WOS:000333205200064 ER PT S AU Madigan, D Stang, PE Berlin, JA Schuemie, M Overhage, JM Suchard, MA Dumouchel, B Hartzema, AG Ryan, PB AF Madigan, David Stang, Paul E. Berlin, Jesse A. Schuemie, Martijn Overhage, J. Marc Suchard, Marc A. Dumouchel, Bill Hartzema, Abraham G. Ryan, Patrick B. BE Fienberg, SE TI A Systematic Statistical Approach to Evaluating Evidence from Observational Studies SO ANNUAL REVIEW OF STATISTICS AND ITS APPLICATION, VOL 1 SE Annual Review of Statistics and Its Application LA English DT Article; Book Chapter DE pharmacovigilance; epidemiology; data interpretation; statistical; electronic heath records; observational studies ID CHARLSON COMORBIDITY INDEX; MEDICAL OUTCOMES PARTNERSHIP; ACUTE MYOCARDIAL-INFARCTION; IMMORTAL TIME BIAS; HEALTH-CARE DATA; ICD CODE 410; ADMINISTRATIVE DATA; CLAIMS DATA; RISK ADJUSTMENT; UNMEASURED CONFOUNDERS AB Threats to the validity of observational studies on the effects of interventions raise questions about the appropriate role of such studies in decision making. Nonetheless, scholarly journals in fields such as medicine, education, and the social sciences feature many such studies, often with limited exploration of these threats, and the lay press is rife with news stories based on these studies. Consumers of these studies rely on the expertise of the study authors to conduct appropriate analyses, and on the thoroughness of the scientific peer-review process to check the validity, but the introspective and ad hoc nature of the design of these analyses appears to elude any meaningful objective assessment of their performance. Here, we review some of the challenges encountered in observational studies and review an alternative, data-driven approach to observational study design, execution, and analysis. Although much work remains, we believe this research direction shows promise. C1 [Madigan, David] Columbia Univ, Dept Stat, New York, NY 10027 USA. [Madigan, David; Stang, Paul E.; Schuemie, Martijn; Overhage, J. Marc; Suchard, Marc A.; Dumouchel, Bill; Hartzema, Abraham G.; Ryan, Patrick B.] Fdn Natl Inst Hlth, Observat Med Outcomes Partnership, Bethesda, MD 20810 USA. [Stang, Paul E.; Schuemie, Martijn; Ryan, Patrick B.] Janssen Res & Dev LLC, Titusville, NJ 08560 USA. [Berlin, Jesse A.] Johnson & Johnson, New Brunswick, NJ 08901 USA. [Overhage, J. Marc] Siemens Hlth Serv, Malvern, PA 19355 USA. [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, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. [Dumouchel, Bill] Oracle Hlth Sci, Burlington, MA 01803 USA. [Hartzema, Abraham G.] Univ Florida, Coll Pharm, Gainesville, FL 32610 USA. RP Madigan, D (reprint author), Columbia Univ, Dept Stat, New York, NY 10027 USA. EM david.madigan@columbia.edu; pstang@its.jnj.com; jberlin@its.jnj.com; mschuemi@its.jnj.com; marc.overhage@siemens.com; msuchard@ucla.edu; bill.dumouchel@oracle.com; hartzema@cop.ufl.edu; pryan4@its.jnj.com NR 94 TC 16 Z9 17 U1 0 U2 22 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 2326-8298 BN 978-0-8243-3950-0 J9 ANNU REV STAT APPL PY 2014 VL 1 BP 11 EP 39 DI 10.1146/annurev-statistics-022513-115645 PG 29 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA BA0HZ UT WOS:000331445900002 ER PT J AU Llorente, AM Brouwers, P Leighty, R Malee, K Smith, R Harris, L Serchuck, LK Blasini, I Chase, C AF Llorente, Antolin M. Brouwers, Pim Leighty, Robert Malee, Kathleen Smith, Renee Harris, Lynnette Serchuck, Leslie K. Blasini, Ileana Chase, Cynthia TI An Analysis of Select Emerging Executive Skills in Perinatally HIV-1-Infected Children SO APPLIED NEUROPSYCHOLOGY-CHILD LA English DT Article DE executive skills; higher-order cognition; HIV; moderating variables; pediatric; psychosocial factors ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY SYNDROME; HIV-INFECTION; INFANTS TRANSMISSION; MOTOR DEVELOPMENT; THERAPY; WOMEN; DISEASE; NEURODEVELOPMENT; ENCEPHALOPATHY AB This study examined the effect of perinatal HIV-1 infection on emerging executive skills in children (n = 161) ages 8 to 12 years. HIV-positive (n = 76) and HIV-negative (n = 85) children were eligible to participate. The HIV-positive children included those who had experienced a CDC Class C event (greater severity, n = 22) and those who were HIV-positive but who had not experienced a CDC Class C event (less severity, n = 54). Measures of emerging executive functions completed by the children included subtests from the Developmental Neuropsychological Assessment (NEPSY), the Trail-Making Test-Part B, and a subtest from the Woodcock-Johnson Battery-Revised. Ratings of executive functions were obtained from caretakers using the Behavior Rating Inventory of Executive Functions. Generalized estimating equations methods, discriminate analyses, and global deficit score analyses were performed to determine whether differences emerged between the three clinical groups while using strict controls. The present results revealed significant group differences in unadjusted mean scores measuring executive functioning. However, such differences did not remain statistically significant when moderating variables were taken into consideration in the models. The apparent deficit in executive functioning for the HIV-positive children was found to be largely due to differential psychosocial and environmental factors rather than HIV disease and its severity, and in this cohort, the effects of HIV-1 infection on emerging executive functions appeared to be negligible when controlling for treatment and moderating psychosocial variables. C1 [Llorente, Antolin M.] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21209 USA. [Brouwers, Pim] NIMH, NIH, Rockville, MD 20857 USA. [Leighty, Robert] Clin Trials & Surveys Corp, Baltimore, MD USA. [Malee, Kathleen] Childrens Mem Hosp, Dept Child & Adolescent Psychiat, Chicago, IL 60614 USA. [Smith, Renee] Univ Illinois, Dept Pediat, Chicago, IL USA. [Harris, Lynnette] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Serchuck, Leslie K.] Eunice Shriver Inst Child Hlth & Human Dev, Pediat Adolescent & Maternal AIDS Branch, Rockville, MD USA. [Blasini, Ileana] Univ Puerto Rico, Dept Pediat, San Juan, PR 00936 USA. [Chase, Cynthia] Boston Med Ctr, Dept Pediat, Boston, MA USA. RP Llorente, AM (reprint author), Univ Maryland, Med Ctr, Mt Washington Pediat Hosp, 1708 West Rogers Ave,Suite 1141, Baltimore, MD 21209 USA. EM allorente@mwph.org NR 59 TC 9 Z9 9 U1 2 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 2162-2965 EI 2162-2973 J9 APPL NEUROPSYCH-CHIL JI Appl. Neuropsychol.-Child PY 2014 VL 3 IS 1 BP 10 EP 25 DI 10.1080/21622965.2012.686853 PG 16 WC Clinical Neurology; Psychology SC Neurosciences & Neurology; Psychology GA AD0TI UT WOS:000332946600002 PM 24236937 ER PT J AU Zou, XN Lin, DM Wan, X Chao, A Feng, QF Dai, Z Yang, GH Lv, N AF Zou Xiao Nong Lin Dong Mei Wan Xia Chao Ann Feng Qin Fu Dai Zhen Yang Gong Huan Lv Ning TI Histological Subtypes of Lung Cancer in Chinese Males from 2000 to 2012 SO BIOMEDICAL AND ENVIRONMENTAL SCIENCES LA English DT Article DE Epidemiology; Lung cancer; Histology ID FILTER CIGARETTE-SMOKING; TRENDS; MORTALITY; EPIDEMIOLOGY; JAPAN; RATES; RISK; ADENOCARCINOMA; COUNTRIES; CESSATION AB Objective To characterize the histological and epidemiological features of male lung cancer patients in China. Methods The demographic and histological information about male lung cancer patients identified from 2000-01-01 to 2012-12-31, was collected from the Cancer Hospital of the Chinese Academy of Medical Sciences. Relative frequencies (RF) were estimated for major histological subtypes and compared according to the years of diagnosis and birth. Results The RF of adenocarcinoma (ADC) increased from 21.96% to 43.36% and the RF of squamous cell carcinoma (SCC) decreased from 39.11% to 32.23% from 2000 to 2012 in the 15 427 male lung cancer patients included in this study (Z=17.909, P<0.0001; Z=-6.117, P<0.0001). The RF of ADC increased from 28.72% in 2000-2004, 36.88% in 2005-2008 to 48.61% in 2009-2012 in patients born after 1960. The age-adjusted RF of ADC in 2007-2012 increased consistently in all the investigated areas. Conclusion The increased RF of ADC in male lung cancer patients highlights the need for further investigation of the etiologic factors of these tumors. Smoke-free policies rather than modifying tobacco products should be enforced. C1 [Zou Xiao Nong; Dai Zhen] Chinese Acad Med Sci, Canc Inst Hosp, Natl Off Canc Prevent & Control, Beijing 100021, Peoples R China. [Lin Dong Mei; Lv Ning] Chinese Acad Med Sci, Dept Pathol, Beijing 100021, Peoples R China. [Wan Xia; Yang Gong Huan] Chinese Acad Med Sci, Inst Basic Med Sci, Ctr Epidemiol & Biostat, Beijing 100005, Peoples R China. [Chao Ann] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA. [Feng Qin Fu] Chinese Acad Med Sci, Dept Radiat Oncol, Beijing 100021, Peoples R China. RP Yang, GH (reprint author), Chinese Acad Med Sci, Canc Inst Hosp, Natl Off Canc Prevent & Control, Beijing 100021, Peoples R China. EM yangghuan@vip.sina.com FU NIH Project 'Epidemiology and Intervention Research for Tobacco Control in China' [R01 RFA-TW-06-006]; Beijing Run-for-Hope Fund [YF2010-48] FX This work was supported by NIH Project 'Epidemiology and Intervention Research for Tobacco Control in China' (R01 RFA-TW-06-006) and Beijing Run-for-Hope Fund (YF2010-48). NR 45 TC 5 Z9 5 U1 1 U2 3 PU CHINESE CENTER DISEASE CONTROL & PREVENTION PI BEIJING PA 155 CHANGBAI RD, CHANGPING DISTRICT, BEIJING, 102206, PEOPLES R CHINA SN 0895-3988 J9 BIOMED ENVIRON SCI JI Biomed. Environ. Sci. PD JAN PY 2014 VL 27 IS 1 BP 3 EP 9 DI 10.3967/bes2014.010 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA AD3WR UT WOS:000333177600002 PM 24553368 ER PT J AU Rujirojindakul, P Flegel, WA AF Rujirojindakul, Pairaya Flegel, Willy A. TI Applying molecular immunohaematology to regularly transfused thalassaemic patients in Thailand SO BLOOD TRANSFUSION LA English DT Article DE blood group; red cell genotyping; dry matching; thalassaemia; Thailand ID SICKLE-CELL-DISEASE; PCR-SSP TECHNIQUE; BLOOD-GROUP; JK(A-B-) PHENOTYPE; DNA; ALLOIMMUNIZATION; DONORS; GENE; ABO; POPULATIONS AB Background. Red blood cell transfusion is the principal therapy in patients with severe thalassaemias and haemoglobinopathies, which are prevalent in Thailand. Serological red blood cell typing is confounded by chronic transfusion, because of circulating donor red blood cells. We evaluated the concordance of serological phenotypes between a routine and a reference laboratory and with red cell genotyping. Materials and methods. Ten consecutive Thai patients with beta-thalassemia major who received regular transfusions were enrolled in Thailand. Phenotypes were tested serologically at Songklanagarind Hospital and at the National Institutes of Health. Red blood cell genotyping was performed with commercially available kits and a platform. Results. In only three patients was the red cell genotyping concordant with the serological phenotypes for five antithetical antigen pairs in four blood group systems at the two institutions. At the National Institutes of Health, 32 of the 100 serological tests yielded invalid or discrepant results. The positive predictive value of serology did not reach 1 for any blood group system at either of the two institutions in this set of ten patients. D iscussion. Within this small study, numerous discrepancies were observed between serological phenotypes at the two institutes; red cell genotyping enabled determination of the blood group when serology failed due to transfused red blood cells. We question the utility of serological tests in regularly transfused paediatric patients and propose relying solely on red cell genotyping, which requires training for laboratory personnel and physicians. Red cell genotyping outperformed red cell serology by an order of magnitude in regularly transfused patients. C1 [Rujirojindakul, Pairaya; Flegel, Willy A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Rujirojindakul, Pairaya] Prince Songkla Univ, Fac Med, Dept Pathol, Hat Yai, Thailand. RP Flegel, WA (reprint author), NIH, Lab Serv Sect, Dept Transfus Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. EM bill.flegel@nih.gov FU American Society of Hematology (ASH); Faculty of Medicine, Prince of Songkla University; Intramural Research Program of the NIH Clinical Center FX Pairaya Rujirojindakul performed this work as Visiting Trainee at the Department of Transfusion Medicine, NIH Clinical Center from October to December 2012 and was supported by the 2012 Visitor Training Program from the American Society of Hematology (ASH) and Faculty of Medicine, Prince of Songkla University. Additional support came from the Intramural Research Program of the NIH Clinical Center. NR 58 TC 9 Z9 9 U1 0 U2 5 PU SIMITI SERVIZI SRL PI MILAN PA VIA DESIDERIO 21, MILAN, 20131, ITALY SN 1723-2007 J9 BLOOD TRANSFUS-ITALY JI Blood Transf. PD JAN PY 2014 VL 12 IS 1 BP 28 EP 35 DI 10.2450/2013.0058-13 PG 8 WC Hematology SC Hematology GA AC1OR UT WOS:000332266400007 PM 24120606 ER PT J AU Flegel, WA Wagner, FF AF Flegel, Willy A. Wagner, Franz F. TI Two molecular polymorphisms to detect the (C)ce(s) type 1 haplotype SO BLOOD TRANSFUSION LA English DT Letter ID WEAK C; PHENOTYPE; GENE C1 [Flegel, Willy A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Wagner, Franz F.] Inst Springe, DRK Blood Donor Serv NSTOB, Springe, Germany. RP Flegel, WA (reprint author), NIH, Lab Serv Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. EM bill.flegel@nih.gov NR 7 TC 1 Z9 1 U1 0 U2 1 PU SIMITI SERVIZI SRL PI MILAN PA VIA DESIDERIO 21, MILAN, 20131, ITALY SN 1723-2007 J9 BLOOD TRANSFUS-ITALY JI Blood Transf. PD JAN PY 2014 VL 12 IS 1 BP 136 EP 137 DI 10.2450/2013.0149-13 PG 2 WC Hematology SC Hematology GA AC1OR UT WOS:000332266400029 PM 24333080 ER PT J AU Marino, P AF Marino, Pamela TI The promise of glycomics for discovery of new biomarkers SO CANCER BIOMARKERS LA English DT Editorial Material C1 NIGMS, Biochem & Biorelated Chem Branch, Pharmacol Physiol & Biol Chem Div, NIH, Bethesda, MD USA. RP Marino, P (reprint author), NIGMS, Biochem & Biorelated Chem Branch, Pharmacol Physiol & Biol Chem Div, NIH, Bethesda, MD USA. EM marinop@nigms.nih.gov NR 0 TC 2 Z9 2 U1 1 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 EI 1875-8592 J9 CANCER BIOMARK JI Cancer Biomark. PY 2014 VL 14 IS 1 BP 1 EP 1 DI 10.3233/CBM-140398 PG 1 WC Oncology SC Oncology GA AD2QE UT WOS:000333079400001 PM 24643037 ER PT J AU Krasnewich, D AF Krasnewich, Donna TI Human glycosylation disorders SO CANCER BIOMARKERS LA English DT Article DE Glycosylation; glycobiology; congenital disorders of glycosylation ID CONGENITAL MUSCULAR-DYSTROPHIES; DEFICIENT GLYCOPROTEIN SYNDROME; THROMBOSPONDIN TYPE-1 REPEATS; PETERS-PLUS SYNDROME; IA CDG-IA; MENTAL-RETARDATION; LINKED OLIGOSACCHARIDES; MUTATIONS; DEFECT; BIOSYNTHESIS AB Over the past 20 years, clinical disorders of glycosylation have expanded to include over 50 recognized defects in the network of glycobiologic pathways. In parallel, more cases have been recognized by astute clinicians increasing both the number of known affected individuals as well as the breadth of clinical features attributed to these disorders. The descriptions of affected individuals may include a functional adult with cognitive impairments, a developmentally normal child with significant gastrointestinal symptoms, a severely ill infant or a fetus with hydrops fetalis. These clinical cases have led to the recognition of gene mutations affecting different enzymes and transporters active in the interconnected synthetic pathways of the myriad of oligosaccharides with essential roles in human development and biology. C1 NIGMS, NIH, Bethesda, MD 20892 USA. RP Krasnewich, D (reprint author), NIGMS, NIH, Bldg 45 Room 2As25h, Bethesda, MD 20892 USA. EM dkras@nigms.nih.gov NR 66 TC 5 Z9 5 U1 1 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 EI 1875-8592 J9 CANCER BIOMARK JI Cancer Biomark. PY 2014 VL 14 IS 1 BP 3 EP 16 DI 10.3233/CBM-130374 PG 14 WC Oncology SC Oncology GA AD2QE UT WOS:000333079400002 PM 24643038 ER PT J AU Muthana, SM Gildersleeve, JC AF Muthana, Saddam M. Gildersleeve, Jeffrey C. TI Glycan microarrays: Powerful tools for biomarker discovery SO CANCER BIOMARKERS LA English DT Article DE Carbohydrate; biomarker; antibodies; glycomics; glycan microarray ID IMMUNODEFICIENCY-VIRUS TYPE-1; RESISTANT PROSTATE-CANCER; INFLUENZA-VIRUSES; SERUM ANTIBODIES; BREAST-CANCER; BURKHOLDERIA-PSEUDOMALLEI; CARBOHYDRATE MICROARRAYS; MULTIPLE-SCLEROSIS; BACILLUS-ANTHRACIS; CONJUGATE VACCINE AB Over the last 10 years, glycan microarray technology has emerged as a powerful high-throughput tool for studying the interactions of carbohydrates with a variety of biomolecules. The array format allows one to screen thousands of binding interactions in a single experiment using minimal amounts of scarce materials. More recently, this technology has been applied to the discovery of biomarkers for diagnosis, prognosis, risk prediction, and monitoring immune responses. Biomarker discovery using glycan arrays has primarily focused on monitoring changes to the anti-glycan antibody repertoires in serum, since the populations of antibodies can change significantly with the onset of disease, exposure to pathogens, or vaccination. Herein, we review efforts to use glycan arrays to identify new biomarkers for cancer, infections, autoimmune diseases, and immune responses. C1 [Muthana, Saddam M.; Gildersleeve, Jeffrey C.] Frederick Natl Lab Canc Res, Biol Chem Lab, Frederick, MD USA. RP Gildersleeve, JC (reprint author), NCI, Chem Biol Lab, Frederick Natl Lab Canc Res, NIH, 376 Boyles St, Frederick, MD 21702 USA. EM gildersj@mail.nih.gov RI Gildersleeve, Jeffrey/N-3392-2014 FU NIH, NCI FX This research was supported by the Intramural Research Program of the NIH, NCI. We thank Christopher Campbell for his contribution to Fig. 3. NR 88 TC 7 Z9 7 U1 3 U2 26 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 EI 1875-8592 J9 CANCER BIOMARK JI Cancer Biomark. PY 2014 VL 14 IS 1 BP 29 EP 41 DI 10.3233/CBM-130383 PG 13 WC Oncology SC Oncology GA AD2QE UT WOS:000333079400004 PM 24643040 ER PT J AU Bachran, C Hasikova, R Leysath, CE Sastalla, I Zhang, Y Fattah, RJ Liu, S Leppla, SH AF Bachran, C. Hasikova, R. Leysath, C. E. Sastalla, I. Zhang, Y. Fattah, R. J. Liu, S. Leppla, S. H. TI Cytolethal distending toxin B as a cell-killing component of tumor-targeted anthrax toxin fusion proteins SO CELL DEATH & DISEASE LA English DT Article DE immunotoxin; targeted toxin; anthrax; drug delivery; cytolethal distending toxin ID BACTERIAL GENOTOXIN; LETHAL FACTOR; IN-VIVO; APOPTOSIS; PHOSPHATASE; IMMUNOTOXIN; INHIBITION; DELIVERY; STRAIN; DNASE AB Cytolethal distending toxin (Cdt) is produced by Gram-negative bacteria of several species. It is composed of three subunits, CdtA, CdtB, and CdtC, with CdtB being the catalytic subunit. We fused CdtB from Haemophilus ducreyi to the N-terminal 255 amino acids of Bacillus anthracis toxin lethal factor (LFn) to design a novel, potentially potent antitumor drug. As a result of this fusion, CdtB was transported into the cytosol of targeted cells via the efficient delivery mechanism of anthrax toxin. The fusion protein efficiently killed various human tumor cell lines by first inducing a complete cell cycle arrest in the G2/M phase, followed by induction of apoptosis. The fusion protein showed very low toxicity in mouse experiments and impressive antitumor effects in a Lewis Lung carcinoma model, with a 90% cure rate. This study demonstrates that efficient drug delivery by a modified anthrax toxin system combined with the enzymatic activity of CdtB has great potential as anticancer treatment and should be considered for the development of novel anticancer drugs. C1 [Bachran, C.; Hasikova, R.; Leysath, C. E.; Sastalla, I.; Zhang, Y.; Fattah, R. J.; Liu, S.; Leppla, S. H.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM sleppla@niaid.nih.gov FU Intramural Research Program of the NIH; National Institute of Allergy and Infectious Diseases (NIAID); Bethesda, MD, USA; Eric Anderson (NIDDK); Margery Smelkinson (NIAID; Owen Schwartz (NIAID) FX This research was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA. We thank Suzanne Abdelazim for her support, Eric Anderson (NIDDK) for mass spectrometric analysis of the proteins described here, Margery Smelkinson (NIAID) and Owen Schwartz (NIAID) for confocal laser scanning microscopy analyses and Kevin Holmes (NIAID) for help with flow cytometry analyses. NR 34 TC 10 Z9 11 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD JAN PY 2014 VL 5 AR e1003 DI 10.1038/cddis.2013.540 PG 9 WC Cell Biology SC Cell Biology GA AC0YZ UT WOS:000332222700027 PM 24434511 ER PT S AU Chachra, SK Xue, ZY Antani, S Demner-Fushman, D Thoma, GR AF Chachra, Suchet K. Xue, Zhiyun Antani, Sameer Demner-Fushman, Dina Thoma, George R. BE Couasnon, B Ringger, EK TI Extraction and Labeling High-resolution Images from PDF Documents SO DOCUMENT RECOGNITION AND RETRIEVAL XXI SE Proceedings of SPIE LA English DT Proceedings Paper CT 21st Conference on Document Recognition and Retrieval (DRR) held as part of IS and T/SPIE Symposium on Electronic Imaging CY FEB 05-06, 2014 CL San Francisco, CA SP Soc Imaging Sci & Technol, SPIE DE Image matching; PDF image extraction AB Accuracy of content-based image retrieval is affected by image resolution among other factors. Higher resolution images enable extraction of image features that more accurately represent the image content. In order to improve the relevance of search results for our biomedical image search engine, Open-I, we have developed techniques to extract and label high-resolution versions of figures from biomedical articles supplied in the PDF format. Open-I uses the open-access subset of biomedical articles from the PubMed Central repository hosted by the National Library of Medicine. Articles are available in XML and in publisher supplied PDF formats. As these PDF documents contain little or no meta-data to identify the embedded images, the task includes labeling images according to their figure number in the article after they have been successfully extracted. For this purpose we use the labeled small size images provided with the XML web version of the article. This paper describes the image extraction process and two alternative approaches to perform image labeling that measure the similarity between two images based upon the image intensity projection on the coordinate axes and similarity based upon the normalized cross-correlation between the intensities of two images. Using image identification based on image intensity projection, we were able to achieve a precision of 92.84% and a recall of 82.18% in labeling of the extracted images. C1 [Chachra, Suchet K.; Xue, Zhiyun; Antani, Sameer; Demner-Fushman, Dina; Thoma, George R.] US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Chachra, SK (reprint author), US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 10 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9938-7 J9 PROC SPIE PY 2014 VL 9021 AR 90210Q DI 10.1117/12.2042336 PG 9 WC Computer Science, Interdisciplinary Applications; Optics SC Computer Science; Optics GA BA1YS UT WOS:000333185000024 ER PT S AU You, D Antani, S Demner-Fushman, D Thoma, GR AF You, Daekeun Antani, Sameer Demner-Fushman, Dina Thoma, George R. BE Couasnon, B Ringger, EK TI A Contour-based Shape Descriptor for Biomedical Image Classification and Retrieval SO DOCUMENT RECOGNITION AND RETRIEVAL XXI SE Proceedings of SPIE LA English DT Proceedings Paper CT 21st Conference on Document Recognition and Retrieval (DRR) held as part of IS and T/SPIE Symposium on Electronic Imaging CY FEB 05-06, 2014 CL San Francisco, CA SP Soc Imaging Sci & Technol, SPIE DE shape representation; contour feature extraction; biomedical image classification; content-based image retrieval AB Contours, object blobs, and specific feature points are utilized to represent object shapes and extract shape descriptors that can then be used for object detection or image classification. In this research we develop a shape descriptor for biomedical image type (or, modality) classification. We adapt a feature extraction method used in optical character recognition (OCR) for character shape representation, and apply various image preprocessing methods to successfully adapt the method to our application. The proposed shape descriptor is applied to radiology images (e.g., MRI, CT, ultrasound, X-ray, etc.) to assess its usefulness for modality classification. In our experiment we compare our method with other visual descriptors such as CEDD, CLD, Tamura, and PHOG that extract color, texture, or shape information from images. The proposed method achieved the highest classification accuracy of 74.1% among all other individual descriptors in the test, and when combined with CSD (color structure descriptor) showed better performance (78.9%) than using the shape descriptor alone. C1 [You, Daekeun; Antani, Sameer; Demner-Fushman, Dina; Thoma, George R.] NIH, Natl Lib Med, Bethesda, MD 20894 USA. RP You, D (reprint author), NIH, Natl Lib Med, Bethesda, MD 20894 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 17 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9938-7 J9 PROC SPIE PY 2014 VL 9021 AR 90210L DI 10.1117/12.2042526 PG 12 WC Computer Science, Interdisciplinary Applications; Optics SC Computer Science; Optics GA BA1YS UT WOS:000333185000019 ER PT J AU Mukherjee, N Jacobs, NC Hafner, M Kennington, EA Nusbaum, JD Tuschl, T Blackshear, PJ Ohler, U AF Mukherjee, Neelanjan Jacobs, Nicholas C. Hafner, Markus Kennington, Elizabeth A. Nusbaum, Jeffrey D. Tuschl, Thomas Blackshear, Perry J. Ohler, Uwe TI Global target mRNA specification and regulation by the RNA-binding protein ZFP36 SO GENOME BIOLOGY LA English DT Article ID AU-RICH ELEMENT; ZINC-FINGER DOMAIN; T-CELL-ACTIVATION; WIDE ANALYSIS; PAR-CLIP; UNTRANSLATED REGIONS; SEQUENCE ELEMENTS; ELAV PROTEIN; HUMAN GENOME; TRISTETRAPROLIN AB Background: ZFP36, also known as tristetraprolin or TTP, and ELAVL1, also known as HuR, are two disease-relevant RNA-binding proteins (RBPs) that both interact with AU-rich sequences but have antagonistic roles. While ELAVL1 binding has been profiled in several studies, the precise in vivo binding specificity of ZFP36 has not been investigated on a global scale. We determined ZFP36 binding preferences using cross-linking and immunoprecipitation in human embryonic kidney cells, and examined the combinatorial regulation of AU-rich elements by ZFP36 and ELAVL1. Results: Targets bound and negatively regulated by ZFP36 include transcripts encoding proteins necessary for immune function and cancer, and transcripts encoding other RBPs. Using partial correlation analysis, we were able to quantify the association between ZFP36 binding sites and differential target RNA abundance upon ZFP36 overexpression independent of effects from confounding features. Genes with increased mRNA half-lives in ZFP36 knockout versus wild-type mouse cells were significantly enriched for our human ZFP36 targets. We identified thousands of overlapping ZFP36 and ELAVL1 binding sites, in 1,313 genes, and found that ZFP36 degrades transcripts through specific AU-rich sequences, representing a subset of the U-rich sequences ELAVL1 interacts with to stabilize transcripts. Conclusions: ZFP36-RNA target specificities in vivo are quantitatively similar to previously reported in vitro binding affinities. ZFP36 and ELAVL1 bind an overlapping spectrum of RNA sequences, yet with differential relative preferences that dictate combinatorial regulatory potential. Our findings and methodology delineate an approach to unravel in vivo combinatorial regulation by RNA-binding proteins. C1 [Mukherjee, Neelanjan; Jacobs, Nicholas C.; Ohler, Uwe] Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, D-13125 Berlin, Germany. [Kennington, Elizabeth A.; Blackshear, Perry J.] Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. [Hafner, Markus; Nusbaum, Jeffrey D.; Tuschl, Thomas] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. [Hafner, Markus; Nusbaum, Jeffrey D.; Tuschl, Thomas] Rockefeller Univ, Lab RNA Mol Biol, New York, NY 10065 USA. RP Mukherjee, N (reprint author), Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Robert Rossle Str 10, D-13125 Berlin, Germany. EM neelanjan.mukherjee@mdc-berlin.de; uwe.ohler@mdc-berlin.de OI Jacobs, Nicholas/0000-0002-2617-6173; Nusbaum, Jeffrey/0000-0001-5024-8256; Mukherjee, Neelanjan/0000-0003-0017-1400; Hafner, Markus/0000-0002-4336-6518 FU US National Institutes of Health [R01-GM104962]; EU Marie Curie IIF (EU); NIH, NIEHS FX TT and UO acknowledge support from an award by the US National Institutes of Health (R01-GM104962). NM is supported by EU Marie Curie IIF (EU). PJB acknowledges support from the Intramural Research Program of the NIH, NIEHS. We would like to acknowledge Jack Keene for very insightful early discussions and suggestions. NR 62 TC 33 Z9 33 U1 3 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2014 VL 15 IS 1 SI SI AR R12 DI 10.1186/gb-2014-15-1-r12 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AD0MC UT WOS:000332927100012 PM 24401661 ER PT J AU Ferreira, Z Hurle, B Andres, AM Kretzschmar, WW Mullikin, JC Cherukuri, PF Cruz, P Hyma, KE Gonder, MK Stone, AC Tishkoff, S Swanson, WJ Green, ED Clark, AG Seixas, S AF Ferreira, Zelia Hurle, Belen Andres, Aida M. Kretzschmar, Warren W. Mullikin, James C. Cherukuri, Praveen F. Cruz, Pedro Hyma, Katie E. Gonder, Mary Katherine Stone, Anne C. Tishkoff, Sarah Swanson, Willie J. Green, Eric D. Clark, Andrew G. Seixas, Susana CA NISC Comparative Sequencing Progra TI Sequence Diversity of Pan troglodytes Subspecies and the Impact of WFDC6 Selective Constraints in Reproductive Immunity (vol 5, pg 2512, 2013) SO GENOME BIOLOGY AND EVOLUTION LA English DT Correction C1 [Ferreira, Zelia; Hurle, Belen; Green, Eric D.] NHGRI, NIH, Bethesda, MD 20892 USA. [Ferreira, Zelia; Seixas, Susana] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Oporto, Portugal. [Ferreira, Zelia] Univ Porto, Fac Sci, Dept Zool & Anthropol, P-4100 Oporto, Portugal. [Ferreira, Zelia] Univ Pittsburgh, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA. [Andres, Aida M.] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, Leipzig, Germany. [Kretzschmar, Warren W.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Mullikin, James C.; Cherukuri, Praveen F.; Cruz, Pedro; NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr NISC, NIH, Bethesda, MD 20892 USA. [Hyma, Katie E.] Cornell Univ, Inst Biotechnol, Bioinformat Facil, Ithaca, NY 14853 USA. [Gonder, Mary Katherine] Drexel Univ, Dept Biol, Philadelphia, PA USA. [Stone, Anne C.] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA. [Tishkoff, Sarah] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. [Tishkoff, Sarah] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. [Swanson, Willie J.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Clark, Andrew G.] Cornell Univ, Dept Biol Mol Biol & Genet, Ithaca, NY 14853 USA. RP Ferreira, Z (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2014 VL 6 IS 2 BP 406 EP 406 DI 10.1093/gbe/evu029 PG 1 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA AC7VZ UT WOS:000332742300013 ER PT J AU Uhlemann, AC Otto, M Lowy, FD Deleo, FR AF Uhlemann, Anne-Catrin Otto, Michael Lowy, Franklin D. Deleo, Frank R. TI Evolution of community- and healthcare-associated methicillin-resistant Staphylococcus aureus SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Staphylococcus aureus; MRSA; Epidemic; Genome sequencing; Antimicrobial resistance ID PANTON-VALENTINE LEUKOCIDIN; CATABOLIC MOBILE ELEMENT; COMPLETE GENOME SEQUENCE; QUORUM-SENSING SYSTEM; UNITED-STATES; MOLECULAR CHARACTERIZATION; ANTIMICROBIAL RESISTANCE; VIRULENCE DETERMINANTS; ANTIBIOTIC-RESISTANCE; CHANGING EPIDEMIOLOGY AB Staphylococcus aureus is a prominent cause of human infections globally. The high prevalence of infections is compounded by antibiotic resistance-a significant problem for treatment. Methicillin-resistant S. aureus (MRSA) is endemic in hospitals and healthcare facilities worldwide, and is an increasingly common cause of community-associated bacterial infections in industrialized countries. Although much focus is placed on the role of S. aureus as a human pathogen, it is in fact a human commensal organism that has had a relatively long coexistence with the human host. Many S. aureus infections can be explained by host susceptibility or other predisposing risk factors. On the other hand, the emergence/re-emergence of successful S. aureus clones (referred to as epidemic waves) suggests a rapid bacterial adaption and evolution, which includes the emergence of antibiotic resistance and increased virulence and/or transmissibility. It is within this context that we review our understanding of selected S. aureus epidemic waves, and highlight the use of genome sequencing as a means to better understand the evolution of each lineage. (C) 2013 Elsevier B.V. Published by Elsevier B.V. All rights reserved. C1 [Uhlemann, Anne-Catrin; Lowy, Franklin D.] Columbia Univ, Coll Phys & Surg, Dept Med, Div Infect Dis, New York, NY USA. [Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, Bethesda, MD 20892 USA. [Deleo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Deleo, FR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516; Otto, Michael/0000-0002-2222-4115 FU US National Institutes of Health [K08 AI090013, R01 AI077690]; Paul A. Marks Scholarship; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, US National Institutes of Health FX This work was supported by the US National Institutes of Health (K08 AI090013 to ACU, and R01 AI077690 and R01 AI077690 to FDL), a Paul A. Marks Scholarship (to ACU), and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, US National Institutes of Health (MO and FRD). NR 134 TC 38 Z9 38 U1 1 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 EI 1567-7257 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD JAN PY 2014 VL 21 BP 563 EP 574 DI 10.1016/j.meegid.2013.04.030 PG 12 WC Infectious Diseases SC Infectious Diseases GA AC1RN UT WOS:000332273800073 PM 23648426 ER PT J AU Ahlman, MA Nietert, PJ Wahlquist, AE Serguson, JM Berry, MW Suranyi, P Liu, ST Spicer, KM AF Ahlman, Mark A. Nietert, Paul J. Wahlquist, Amy E. Serguson, Jill M. Berry, Max W. Suranyi, Pal Liu, Songtao Spicer, Kenneth M. TI A single CT for attenuation correction of both rest and stress SPECT myocardial perfusion imaging: a retrospective feasibility study SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE LA English DT Article DE Tomography; emission-computed; single-photon; myocardial perfusion imaging; "reproducibility of results"; tomography; X-ray computed; radiation dosage ID ROUTINE CLINICAL-PRACTICE; EJECTION FRACTION; IMAGES; MISREGISTRATION; REREGISTRATION; REGISTRATION; CARDIOLOGY; STATEMENT; ERRORS; PET/CT AB Purpose: In the effort to reduce radiation exposure to patients undergoing myocardial perfusion imaging (MPI) with SPECT/CT, we evaluate the feasibility of a single CT for attenuation correction (AC) of single-day rest (R)/stress (S) perfusion. Methods: Processing of 20 single isotope and 20 dual isotope MPI with perfusion defects were retrospectively repeated in three steps: (1) the standard method using a concurrent R-CT for AC of R-SPECT and S-CT for S-SPECT; (2) the standard method repeated; and (3) with the R-CT used for AC of S-SPECT, and the S-CT used for AC of R-SPECT. Intra-Class Correlation Coefficients (ICC) and Choen's kappa were used to measure intra-operator variability in sum scoring. Results: The highest level of intra-operator reliability was seen with the reproduction of the sum rest score (SRS) and sum stress score (SSS) (ICC > 95%). ICCs were > 85% for SRS and SSS when alternate CTs were used for AC, but when sum difference scores were calculated, ICC values were much lower (similar to 22% to 27%), which may imply that neither CT substitution resulted in a reproducible difference score. Similar results were seen when evaluating dichotomous outcomes (sum scores difference of >= 4) when comparing different processing techniques (kappas similar to 0.32 to 0.43). Conclusions: When a single CT is used for AC of both rest and stress SPECT, there is disproportionately high variability in sum scoring that is independent of user error. This information can be used to direct further investigation in radiation reduction for common imaging exams in nuclear medicine. C1 [Ahlman, Mark A.; Liu, Songtao] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Nietert, Paul J.; Wahlquist, Amy E.] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Serguson, Jill M.; Berry, Max W.; Suranyi, Pal; Spicer, Kenneth M.] Med Univ S Carolina, Dept Radiol & Radiol Sci, Charleston, SC 29425 USA. RP Ahlman, MA (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. EM mark.ahlman@gmail.com FU Imaging Sciences Training Program at the NIH; National Center for Research Resources [UL1RR029882]; National Institutes of Health FX For their hard work and support we would like to thank David Davison, Leonie Gordon, Blaine Mischen, and the friendly and knowledgeable technologist and support staff at the Medical University of South Carolina. This work is supported by the Imaging Sciences Training Program at the NIH. In addition, by award number UL1RR029882 from the National Center for Research Resources which is funded by the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health. NR 28 TC 2 Z9 2 U1 0 U2 5 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1940-5901 J9 INT J CLIN EXP MED JI Int. J. Clin. Exp. Med. PY 2014 VL 7 IS 1 BP 148 EP 155 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AD3MW UT WOS:000333151200018 PM 24482701 ER PT J AU Prasad, V Rho, J Cifu, A AF Prasad, Vinay Rho, Jason Cifu, Adam TI Further Thoughts on Why There Are Good Data Supporting the Inferior Vena Cava Filter SO JAMA INTERNAL MEDICINE LA English DT Letter ID PULMONARY-EMBOLISM; PREVENTION C1 [Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Rho, Jason] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Cifu, Adam] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr,10-12N226, Bethesda, MD 20892 USA. EM vinayak.prasad@nih.gov NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2014 VL 174 IS 1 BP 164 EP 165 DI 10.1001/jamainternmed.2013.13176 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AD2EM UT WOS:000333046500053 PM 24394930 ER PT J AU Gubin, MM Techasintana, P Magee, JD Dahm, GM Calaluce, R Martindale, JL Whitney, MS Franklin, CL Besch-Williford, C Hollingsworth, JW Abdelmohsen, K Gorospe, M Atasoy, U AF Gubin, Matthew M. Techasintana, Patsharaporn Magee, Joseph D. Dahm, Garrett M. Calaluce, Robert Martindale, Jennifer L. Whitney, Maryln S. Franklin, Craig L. Besch-Williford, Cindy Hollingsworth, John W. Abdelmohsen, Kotb Gorospe, Myriam Atasoy, Ulus TI Conditional Knockout of the RNA-Binding Protein HuR in CD4(+) T Cells Reveals a Gene Dosage Effect on Cytokine Production SO MOLECULAR MEDICINE LA English DT Article ID MESSENGER-RNA; TH2 DIFFERENTIATION; ALLERGIC-ASTHMA; BREAST-CANCER; POSTTRANSCRIPTIONAL REGULATION; EXPRESSION; INFLAMMATION; ACTIVATION; RESPONSES; MOUSE AB The posttranscriptional mechanisms by which RNA binding proteins (RBPs) regulate T-cell differentiation and cytokine production in vivo remain unclear. The RBP HuR binds to labile mRNAs, usually leading to increases in mRNA stability and/or translation. Previous work demonstrated that HuR binds to the mRNAs encoding the Th2 transcription factor trans-acting T-cell-specific transcription factor (GATA-3) and Th2 cytokines interleukin (IL)-4 and IL-13, thereby regulating their expression. By using a novel conditional HuR knockout (KO) mouse in which HuR is deleted in activated T cells, we show that Th2-polarized cells from heterozygous HuR conditional (OX40-Cre HuR(fl/+)) KO mice had decreased steady-state levels of Gata3, II4 and II13 mRNAs with little changes at the protein level. Surprisingly, Th2-polarized cells from homozygous HuR conditional (OX40-Cre HuR(fl/fl)) KO mice showed increased II2, II4 and II13 mRNA and protein via different mechanisms. Specifically, II4 was transcriptionally upregulated in HuR KO T cells, whereas II2 and II13 mRNA stabilities increased. Additionally, when using the standard ovalbumin model of allergic airway inflammation, HuR conditional KO mice mounted a robust inflammatory response similar to mice with wild-type HuR levels. These results reveal a complex differential posttranscriptional regulation of cytokines by HuR in which gene dosage plays an important role. These findings may have significant implications in allergies and asthma, as well as autoimmune diseases and infection. C1 [Gubin, Matthew M.; Techasintana, Patsharaporn; Magee, Joseph D.; Dahm, Garrett M.; Calaluce, Robert; Whitney, Maryln S.; Franklin, Craig L.; Besch-Williford, Cindy; Atasoy, Ulus] Univ Missouri, Columbia, MO USA. [Martindale, Jennifer L.; Abdelmohsen, Kotb; Gorospe, Myriam] NIA, NIH, Baltimore, MD 21224 USA. [Hollingsworth, John W.] Duke Univ, Dept Med, Durham, NC USA. RP Atasoy, U (reprint author), One Hosp Dr,M610C, Columbia, MO 65212 USA. EM atasoyu@missouri.edu FU National Institutes of Health [R01AI080870-01, R21AI079341-01]; National Institute on Aging Intramural Research Program, National Institutes of Health (NIA, IRP, NIH) FX This work was supported by National Institutes of Health grants R01AI080870-01 and R21AI079341-01 (to U Atasoy). M Gorospe, K Abdelmohsen and JL Martindale were kindly supported by the National Institute on Aging Intramural Research Program, National Institutes of Health (NIA, IRP, NIH). NR 64 TC 7 Z9 7 U1 0 U2 4 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 EI 1528-3658 J9 MOL MED JI Mol. Med. PD JAN-JUN PY 2014 VL 20 BP 93 EP 108 DI 10.2119/molmed.2013.00127 PG 16 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AD3VF UT WOS:000333173600011 PM 24477678 ER PT J AU Cui, Y Osorio, JC Risquez, C Wang, H Shi, Y Gochuico, BR Morse, D Rosas, IO El-Chemaly, S AF Cui, Ye Osorio, Juan C. Risquez, Cristobal Wang, Hao Shi, Ying Gochuico, Bernadette R. Morse, Danielle Rosas, Ivan O. El-Chemaly, Souheil TI Transforming Growth Factor-beta 1 Downregulates Vascular Endothelial Growth Factor-D Expression in Human Lung Fibroblasts via the Jun NH2-Terminal Kinase Signaling Pathway SO MOLECULAR MEDICINE LA English DT Article ID IDIOPATHIC PULMONARY-FIBROSIS; NONSPECIFIC INTERSTITIAL PNEUMONIA; COLORECTAL-CANCER PROGRESSION; MESSENGER-RNA STABILITY; VEGF-D EXPRESSION; TGF-BETA; MESENCHYMAL TRANSITION; FACTOR-C; ACTIVATION; LYMPHANGIOGENESIS AB Vascular endothelial growth factor (VEGF)-D, a member of the VEGF family, induces both angiogenesis and lymphangiogene sis by activating VEGF receptor-2 (VEGFR-2) and VEGFR-3 on the surface of endothelial cells. Transforming growth factor (TGF)-beta 1 has been shown to stimulate VEGF-A expression in human lung fibroblast via the Smad3 signaling pathway and to induce VEGF-C in human proximal tubular epithelial cells. However, the effects of TGF-beta 1 on VEGF-D regulation are unknown. To investigate the regulation of VEGF-D, human lung fibroblasts were studied under pro-fibrotic conditions in vitro and in idiopathic pulmonary fibrosis (IPF) lung tissue. We demonstrate that TGF-beta 1 downregulates VEGF-D expression in a dose-and time-dependent manner in human lung fibroblasts. This TGF-beta 1 effect can be abolished by inhibitors of TGF-beta type I receptor kinase and Jun NH2-terminal kinase (JNK), but not by Smad3 knockdown. In addition, VEGF-D knockdown in human lung fibroblasts induces G1/S transition and promotes cell proliferation. Importantly, VEGF-D protein expression is decreased in lung homogenates from IPF patients compared with control lung. In IPF lung sections, fibroblastic foci show very weak VEGF-D immunoreactivity, whereas VEGF-D is abundantly expressed within alveolar interstitial cells in control lung. Taken together, our data identify a novel mechanism for downstream signal transduction induced by TGF-beta 1 in lung fibroblasts, through which they may mediate tissue remodeling in IPF. C1 [Cui, Ye; Osorio, Juan C.; Risquez, Cristobal; Wang, Hao; Shi, Ying; Morse, Danielle; Rosas, Ivan O.; El-Chemaly, Souheil] Harvard Univ, Brigham & Womens Hosp, Div Pulm & Crit Care Med, Sch Med, Boston, MA 02115 USA. [Gochuico, Bernadette R.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP El-Chemaly, S (reprint author), Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. EM sel-chemaly@partners.org FU National Institutes of Health [K22HL092223-A1]; Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health FX This work was supported by National Institutes of Health Grant K22HL092223-A1 (to S El-Chemaly) and in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 61 TC 8 Z9 8 U1 1 U2 5 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 EI 1528-3658 J9 MOL MED JI Mol. Med. PD JAN-JUN PY 2014 VL 20 BP 120 EP 134 DI 10.2119/molmed.2013.00123 PG 15 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AD3VF UT WOS:000333173600013 PM 24515257 ER PT J AU Murphy, AJ Pierce, J de Caestecker, C Ayers, GD Zhao, A Correa, H Krebs, JR Saito-Diaz, VK Lee, E Perantoni, AO de Caestecker, MP Lovvorn, HN AF Murphy, Andrew J. Pierce, Janene de Caestecker, Christian Ayers, Gregory D. Zhao, Alex Correa, Hernan Krebs, Jonathan R. Saito-Diaz, Vincente Kenyi Lee, Ethan Perantoni, Alan O. de Caestecker, Mark P. Lovvorn, Harold N., III TI CITED1 confers stemness to Wilms tumor and enhances tumorigenic responses when enriched in the nucleus SO ONCOTARGET LA English DT Article DE CITED1; Wilms tumor; WNT; WiT49; cancer stem cell ID KIDNEY DEVELOPMENT; GENE-EXPRESSION; SELF-RENEWAL; CELLS; WNT; CANCER; LGR5; ROLES; OVEREXPRESSION; SPECIFICITY AB Wilms tumor (WT) is the most common childhood kidney cancer and retains gene expression profiles reminiscent of the embryonic kidney. We have shown previously that CITED1, a transcriptional regulator that labels the self-renewing, multipotent nephron progenitor population of the developing kidney, is robustly expressed across all major WT disease and patient characteristics. In this malignant context, CITED1 becomes enriched in the nucleus, which deviates from its cytosolic predominance in embryonic nephron progenitors. We designed the current studies to test the functional and mechanistic effects of differential CITED1 subcellular localization on WT behavior. To mimic its subcellular distribution observed in clinical WT specimens, CITED1 was misexpressed ectopically in the human WT cell line, WiT49, as either a wild-type (predominantly cytosolic) or a mutant, but transcriptionally active, protein (two point mutations in its nuclear export signal, CITED1.NES; nuclear-enriched). In vitro analyses showed that CITED1.NES enhanced WiT49 proliferation and colony formation in soft agar relative to wild-type CITED1 and empty vector controls. The nuclear-enriched CITED1.NES cell line showed the greatest tumor volumes after xenotransplantation into immunodeficient mice (n=15 animals per cell line). To elucidate CITED1 gene targets in this model, microarray profiling showed that wildtype CITED1 foremost upregulated LGR5 (stem cell marker), repressed CDH6 (early marker of epithelial commitment of nephron progenitors), and altered expression of specific WNT pathway participants. In summary, forced nuclear enrichment of CITED1 in a human WT cell line appears to enhance tumorigenicity, whereas ectopic cytosolic expression confers stem-like properties and an embryonic phenotype, analogous to the developmental context. C1 [Murphy, Andrew J.; Pierce, Janene; de Caestecker, Christian; Krebs, Jonathan R.; Lovvorn, Harold N., III] Monroe Carell Jr Childrens Hosp Vanderbilt, Dept Pediat Surg, Nashville, TN USA. [Ayers, Gregory D.; Zhao, Alex] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA. [Saito-Diaz, Vincente Kenyi; Lee, Ethan] Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN USA. [Perantoni, Alan O.] NCI, Canc & Dev Biol Lab, Ctr Canc Res, Frederick, MD 21701 USA. [de Caestecker, Mark P.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. [de Caestecker, Mark P.] Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN USA. [Correa, Hernan] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37212 USA. RP Lovvorn, HN (reprint author), Monroe Carell Jr Childrens Hosp Vanderbilt, Dept Pediat Surg, Nashville, TN USA. EM harold.lovvorn@vanderbilt.edu FU NCI [4R00CA135695-03, 5T32CA106183-06A1, RO1GM103926, R01GM081635]; Section of Surgical Sciences; Ingram Cancer Center of the Vanderbilt University Medical Center FX The authors have no conflict of interest to report. This work was supported in part by NCI grants 4R00CA135695-03 (HNL), 5T32CA106183-06A1 (AJM), RO1GM103926 and R01GM081635 (EL), and by the Section of Surgical Sciences and the Ingram Cancer Center of the Vanderbilt University Medical Center. NR 50 TC 8 Z9 8 U1 0 U2 0 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN PY 2014 VL 5 IS 2 BP 386 EP 402 PG 17 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AC7IC UT WOS:000332700400007 PM 24481423 ER PT J AU Gameiro, SR Jammeh, ML Wattenberg, MM Tsang, KY Ferrone, S Hodge, JW AF Gameiro, Sofia R. Jammeh, Momodou L. Wattenberg, Max M. Tsang, Kwong Y. Ferrone, Soldano Hodge, James W. TI Radiation-induced immunogenic modulation of tumor enhances antigen processing and calreticulin exposure, resulting in enhanced T-cell killing SO ONCOTARGET LA English DT Article DE radiation; immunogenic modulation; antigen-processing machinery; calreticulin; CTL; ER stress; PERK; TAP1; TAP2; calnexin; tapasin; LMP2; LMP7; LMP10 ID HUMAN CARCINOEMBRYONIC ANTIGEN; ENDOPLASMIC-RETICULUM; IMMUNE-SYSTEM; ANTICANCER CHEMOTHERAPY; MONOCLONAL-ANTIBODIES; FLOW-CYTOMETRY; DEATH; EXPRESSION; PHENOTYPE; THERAPY AB Radiation therapy (RT) is used for local tumor control through direct killing of tumor cells. Radiation-induced cell death can trigger tumor antigen-specific immune responses, but these are often noncurative. Radiation has been demonstrated to induce immunogenic modulation (IM) in various tumor types by altering the biology of surviving cells to render them more susceptible to T cell-mediated killing. Little is known about the mechanism(s) underlying IM elicited by sub-lethal radiation dosing. We have examined the molecular and immunogenic consequences of radiation exposure in breast, lung, and prostate human carcinoma cells. Radiation induced secretion of ATP and HMGB1 in both dying and surviving tumor cells. In vitro and in vivo tumor irradiation induced significant upregulation of multiple components of the antigen-processing machinery and calreticulin cell-surface expression. Augmented CTL lysis specific for several tumor-associated antigens was largely dictated by the presence of calreticulin on the surface of tumor cells and constituted an adaptive response to endoplasmic reticulum stress, mediated by activation of the unfolded protein response. This study provides evidence that radiation induces a continuum of immunogenic alterations in tumor biology, from immunogenic modulation to immunogenic cell death. We also expand the concept of immunogenic modulation, where surviving tumor cells recovering from radiation-induced endoplasmic reticulum stress become more sensitive to CTL killing. These observations offer a rationale for the combined use of radiation with immunotherapy, including for patients failing RT alone. C1 [Gameiro, Sofia R.; Jammeh, Momodou L.; Wattenberg, Max M.; Tsang, Kwong Y.; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Ferrone, Soldano] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hodge, JW (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM jh241d@nih.gov RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health; PHS [R01 CA110249]; National Cancer Institute FX This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, and by the PHS grant R01 CA110249 (S.F.), awarded by the National Cancer Institute. NR 50 TC 72 Z9 75 U1 1 U2 8 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN PY 2014 VL 5 IS 2 BP 403 EP 416 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AC7IC UT WOS:000332700400008 PM 24480782 ER PT J AU Sklavos, MM Spracklen, CN Saftlas, AF Pinto, LA AF Sklavos, Martha M. Spracklen, Cassandra N. Saftlas, Audrey F. Pinto, Ligia A. TI Does Loop Electrosurgical Excision Procedure of the Uterine Cervix Affect Anti-Mullerian Hormone Levels? SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID ANTIMULLERIAN HORMONE; INTRAEPITHELIAL NEOPLASIA; SERUM MARKER; WOMEN; OVARIAN; AGE; INFLAMMATION; INFERTILITY; FERTILITY; LYMPHOMA AB Background. A delayed time to pregnancy was recently reported for women who had a loop electrosurgical excision procedure (LEEP) to remove cervical intraepithelial neoplasia (CIN) grade 2 or 3. The objective of the current study was to determine if treatment of CIN with LEEP is associated with decreased levels of anti-Mullerian hormone (AMH), a marker of ovarian reserve. Methods. AMH levels were measured in 18 women treated with LEEP and 18 age-matched controls, who had colposcopy only and did not require LEEP. Cases and controls had their blood drawn at study entry time zero and again 6 months later. Results. The mean AMH level decreased significantly from baseline to follow-up; however, no significant differences were observed when stratifying by LEEP status, suggesting that both groups experienced a similar decrease in AMH levels during the follow-up period. Although women treated with LEEP had lower overall AMH levels than controls at both baseline and follow-up, these differences were not statistically significant. Conclusion. Overall, the delayed time to pregnancy observed in women treated with LEEP is likely not due to a LEEP-associated decrease in ovarian reserve as measured by AMH; thus, other mechanism are responsible for the delayed time to pregnancy associated with LEEP. C1 [Sklavos, Martha M.; Pinto, Ligia A.] Leidos Biomed Res Inc, Human Papillomavirus Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Spracklen, Cassandra N.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA. [Saftlas, Audrey F.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA. RP Pinto, LA (reprint author), Leidos Biomed Res Inc, Human Papillomavirus Immunol Lab, Frederick Natl Lab Canc Res, Bldg 469,Room 111,1050 Boyles St, Frederick, MD 21702 USA. EM pintol@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH [5R21A1068111-02] FX The authors thank Mary Cherrico for contributions to the data collection. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract no. HHSN261200800001E. The content of this paper does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US Government. This project was also funded by the NIH Grant 5R21A1068111-02 to Audrey F. Saftlas at the University of Iowa, Iowa City, IA. NR 33 TC 1 Z9 1 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2014 AR 875438 DI 10.1155/2014/875438 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AC7QG UT WOS:000332725200001 ER PT J AU Bouville, A Linet, MS Hatch, M Mabuchi, K Simon, SL AF Bouville, Andre Linet, Martha S. Hatch, Maureen Mabuchi, Kiyohiko Simon, Steven L. TI Guidelines for Exposure Assessment in Health Risk Studies Following a Nuclear Reactor Accident SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID CANCER INCIDENCE; WEAPONS TESTS; RADIATION; PLANT; RESIDENTS; COMMUNICATION; REEVALUATION; FALLOUT; IMPACT; FUTURE AB BACKGROUND: Worldwide concerns regarding health effects after the Chernobyl and Fukushima nuclear power plant accidents indicate a clear need to identify short- and long-term health impacts that might result from accidents in the future. Fundamental to addressing this problem are reliable and accurate radiation dose estimates for the affected populations. The available guidance for activities following nuclear accidents is limited with regard to strategies for dose assessment in health risk studies. OBJECTIVES: Here we propose a comprehensive systematic approach to estimating radiation doses for the evaluation of health risks resulting from a nuclear power plant accident, reflected in a set of seven guidelines. DISCUSSION: Four major nuclear reactor accidents have occurred during the history of nuclear power production. The circumstances leading to these accidents were varied, as were the magnitude of the releases of radioactive materials, the pathways by which persons were exposed, the data collected afterward, and the lifestyle factors and dietary consumption that played an important role in the associated radiation exposure of the affected populations. Accidents involving nuclear reactors may occur in the future under a variety of conditions. The guidelines we recommend here are intended to facilitate obtaining reliable dose estimations for a range of different exposure conditions. We recognize that full implementation of the proposed approach may not always be feasible because of other priorities during the nuclear accident emergency and because of limited resources in manpower and equipment. CONCLUSIONS: The proposed approach can serve as a basis to optimize the value of radiation dose reconstruction following a nuclear reactor accident. C1 [Bouville, Andre] NCI, NIH, DHHS, Rockville, MD 20850 USA. [Linet, Martha S.; Hatch, Maureen; Mabuchi, Kiyohiko; Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20850 USA. RP Simon, SL (reprint author), NCI, 9609 Med Ctr Dr, Rockville, MD 20850 USA. EM ssimon@mail.nih.gov NR 48 TC 6 Z9 6 U1 1 U2 15 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2014 VL 122 IS 1 BP 1 EP 5 DI 10.1289/ehp.1307120 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AC6OT UT WOS:000332644200011 PM 24184886 ER PT J AU Whitehead, GS Thomas, SY Cook, DN AF Whitehead, Gregory S. Thomas, Seddon Y. Cook, Donald N. TI Modulation of Distinct Asthmatic Phenotypes in Mice by Dose-Dependent Inhalation of Microbial Products SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID REGULATORY T-CELLS; AIRWAY HYPERRESPONSIVENESS; ALLERGIC-ASTHMA; ENDOTOXIN; LIPOPOLYSACCHARIDE; INFLAMMATION; RESPONSES; EXPOSURE; INDOOR; HYPERREACTIVITY AB BACKGROUND: Humans with asthma display considerable heterogeneity with regard to T helper (Th) 2-associated eosinophilic and Th17-associated neutrophilic inflammation, but the impact of the environment on these different forms of asthma is poorly understood. OBJECTIVE: We studied the nature and longevity of asthma-like responses triggered by inhalation of allergen together with environmentally relevant doses of inhaled lipopolysaccharide (LPS). METHODS: Ovalbumin (OVA) was instilled into the airways of mice together with a wide range of LPS doses. Following a single OVA challenge, or multiple challenges, animals were assessed for pulmonary cytokine production, airway inflammation, and airway hyperresponsiveness (AHR). RESULTS: Mice instilled with OVA together with very low doses (<= 10(-3) mu g) of LPS displayed modest amounts of Th2 cytokines, with associated airway eosinophilia and AHR after a single challenge, and these responses were sustained after multiple OVA challenges. When the higher but still environmentally relevant dose of 10(-1) mu g LPS was used, mice initially displayed similar Th2 responses, as well as Th17-associated neutrophilia. After multiple OVA challenges, however, the 10(-1) mu g LPS animals also accumulated large numbers of allergen-specific T regulatory (Treg) cells with high levels of inducible co-stimulatory molecule (ICOS). As a result, asthma-like features in these mice were shorter-lived than in mice sensitized using lower doses of LPS. CONCLUSIONS: The nature and longevity of Th2, Th17, and Treg immune responses to inhaled allergen are dependent on the quantity of LPS inhaled at the time of allergic sensitization. These findings might account in part for the heterogeneity of inflammatory infiltrates seen in lungs of asthmatics. C1 [Whitehead, Gregory S.; Thomas, Seddon Y.; Cook, Donald N.] NIEHS, Lab Resp Biol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Cook, DN (reprint author), NIEHS, Lab Resp Biol, NIH, Dept Hlth & Human Serv, 111 T W Alexander Dr,Bldg 101,E244, Res Triangle Pk, NC 27709 USA. EM cookd@niehs.nih.gov OI Thomas, Seddon/0000-0003-0075-0744 FU Intramural Research Program of the National Institutes of Health; National Institute of Environmental Health Sciences FX This work was supported by the Intramural Research Program of the National Institutes of Health and the National Institute of Environmental Health Sciences. NR 35 TC 8 Z9 8 U1 0 U2 7 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2014 VL 122 IS 1 BP 34 EP 42 DI 10.1289/ehp.1307280 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AC6OT UT WOS:000332644200016 PM 24168764 ER PT J AU Guan, SZ Liu, JW Fang, EF Ng, TB Lian, YL Ge, H AF Guan, Su-zhen Liu, Ji-wen Fang, Evandro Fei Ng, Tzi Bun Lian, Yu-long Ge, Hua TI Chronic unpredictable mild stress impairs erythrocyte immune function and changes T-lymphocyte subsets in a rat model of stress-induced depression SO ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Chronic unpredictable mild stress; Depression; Erythrocyte immune function; T-lymphocyte subsets; IL-2 ID RED-BLOOD-CELL; ANIMAL-MODEL; OPEN-FIELD; MICE; DIFFERENTIATION; CORTICOSTERONE; ANESTHESIA; DISORDERS; COMPLEXES; ANXIETY AB Stress has been shown to suppress immune function and increase susceptibility to inflammatory and psychiatric diseases. This study sought to investigate the changes in erythrocyte immune functions and T-lymphocyte subsets and to explore the mechani m implicated in the process of stress-induced depression by employing a rat depression model induced by chronic unpredictable mild stress (CUMS). The body weights and behavioral changes of the rats were recorded, and plasma corticosterone levels were determined by radioimmunoassay. Erythrocyte immune function and T-lymphocytes subsets were respectively measured by the method of yeast rosette and flow cytometry at different time intervals, and their relationship was analyzed. Results indicated that a reduction was observed in the following: the rats' crossing and rearing movement times, the volume of sucrose intake and the preference for sucrose in the depression model group. Plasma corticosterone levels were elevated; the rate of E-C3bR decreased, and E-IC was increased. Some alterations in the percentage of T-lymphocytes and IL-2 appeared in the depression model group and some relationships existed between these parameters. Collectively, these findings disclose that long-time stress could induce changes in rat behavior and activities through an effect on erythrocyte immune functions and T-lymphocyte subsets. Published by Elsevier B.V. C1 [Guan, Su-zhen] Xinjiang Med Univ, Coll Publ Hlth, Dept Social Med, Urumqi 830011, Peoples R China. [Liu, Ji-wen; Ge, Hua] Xinjiang Med Univ, Coll Publ Hlth, Dept Occupat Hlth & Environm Hlth, Urumqi 830011, Peoples R China. [Fang, Evandro Fei] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Ng, Tzi Bun] Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Shatin, Hong Kong, Peoples R China. [Lian, Yu-long] Nantong Univ, Dept Occupat Hlth & Environm Hlth, Coll Publ Hlth, Coll Med, Nantong 226000, Jiangsu, Peoples R China. RP Liu, JW (reprint author), Xinjiang Med Univ, Coll Publ Hlth, Dept Occupat Hlth & Environm Hlth, Urumqi 830011, Peoples R China. EM Liujiwendr@163.com FU Youth Science Fund of Xinjiang Uighur Autonomous Region [2013211B50]; Intramural Research Program of the NIH, National Institute on Aging FX This work was supported by Grants from Youth Science Fund of Xinjiang Uighur Autonomous Region (2013211B50). EFF was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 48 TC 3 Z9 5 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1382-6689 EI 1872-7077 J9 ENVIRON TOXICOL PHAR JI Environ. Toxicol. Pharmacol. PD JAN PY 2014 VL 37 IS 1 BP 414 EP 422 DI 10.1016/j.etap.2013.12.013 PG 9 WC Environmental Sciences; Pharmacology & Pharmacy; Toxicology SC Environmental Sciences & Ecology; Pharmacology & Pharmacy; Toxicology GA AD0JH UT WOS:000332919800046 PM 24448466 ER PT J AU Brell, JM AF Brell, Joanna M. TI Animal Models of Peripheral Neuropathy: Modeling What We Feel, Understanding What They Feel SO ILAR JOURNAL LA English DT Editorial Material ID CHRONIC PAIN; DIABETIC-NEUROPATHY; RISK-FACTORS; LIMB PAIN; NERVE; DEFICIENCY; HEALTH; MECHANISMS; DISEASE; MOUSE C1 [Brell, Joanna M.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Brell, JM (reprint author), 9609 Med Ctr Dr 5E436, Bethesda, MD USA. EM brelljm@mail.nih.gov NR 67 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 EI 1930-6180 J9 ILAR J JI ILAR J. PY 2014 VL 54 IS 3 BP 253 EP 258 DI 10.1093/ilar/ilt056 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA AC8CG UT WOS:000332760000001 PM 24615438 ER PT J AU Rao, DB Jortner, BS Sills, RC AF Rao, Deepa B. Jortner, Bernard S. Sills, Robert C. TI Animal Models of Peripheral Neuropathy Due to Environmental Toxicants SO ILAR JOURNAL LA English DT Article DE acrylamide; carbon disulfide; environmental toxicant; hexacarbon; organophosphate; peripheral neuropathy; pyridoxine; vitamin B-6 ID CARBON-DISULFIDE NEUROTOXICITY; DYING-BACK PROCESS; NERVOUS-SYSTEM; ACRYLAMIDE NEUROPATHY; HEXANE NEUROPATHY; RAT CEREBELLUM; BUTYL KETONE; SPINAL-CORD; EXPOSURE; WORKERS AB Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy-namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B-6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves. C1 [Rao, Deepa B.] NIEHS, Div Natl Toxicol Program, Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. [Jortner, Bernard S.] Virginia Tech, Virginia Maryland Reg Coll Vet Med, Blacksburg, VA USA. [Sills, Robert C.] NIEHS, Cellular & Mol Pathol Branch, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Rao, DB (reprint author), NIEHS, POB 12233,MS B3-06,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM sills@niehs.nih.gov FU Division of the National Toxicology Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS) FX We thank the reviewers, Drs. David E. Malarkey and Arun R. Pandiri, for their input toward the improvement of this article. We are grateful to Emily Singletary for her technical expertise with the image preparation. This research was supported in part by the Division of the National Toxicology Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS). This article may be the work product of an employee or group of employees of the NIEHS, NIH; however, the statements, opinions or conclusions contained therein do not necessarily represent the statements, opinions, or conclusions of the NIEHS, NIH, or US government. NR 89 TC 4 Z9 5 U1 2 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 EI 1930-6180 J9 ILAR J JI ILAR J. PY 2014 VL 54 IS 3 BP 315 EP 323 DI 10.1093/ilar/ilt058 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA AC8CG UT WOS:000332760000008 PM 24615445 ER PT J AU Silk, SB Hampton, LL Brown, PA AF Silk, Susan Brust Hampton, Lori L. Brown, Patricia A. TI What Investigators Need to Know About the Use of Animals SO ILAR JOURNAL LA English DT Article DE animal welfare; assurance; humane; IACUC; investigator; PHS policy AB Investigators conducting research with animal subjects have an ethical and legal responsibility to ensure they are treated humanely. The system of animal research oversight in the United States consists of a framework of federal, state, local, and institutional requirements. Institutions supported by the Public Health Service (PHS) are required to follow the guidelines mandated by the PHS Policy on Humane Care and Use of Laboratory Animals and establish institutional animal care and use committees (IACUC) to oversee animal research activities. This system of self-monitoring at the local level is central to assuring an effective and compliant animal care and use program. Integral to this system is the responsibility of the investigator for the stewardship of their research animal subjects. No activities may be conducted without IACUC approval. Investigators are accountable for all aspects of their animal research activities from preparing their funding applications and complying with the terms and conditions of awards to protecting the investment in research with animals. This review acts as a succinct resource and provides references for investigators supported by the PHS to understand the main expectations and requirements when using animals in research. C1 [Silk, Susan Brust; Hampton, Lori L.; Brown, Patricia A.] NIH, Div Policy & Educ, Off Lab Anim Welf, Bethesda, MD 20892 USA. RP Brown, PA (reprint author), NIH, Off Lab Anim Welf, 6705 Rockledge Dr,Suite 360, Bethesda, MD 20892 USA. EM brownp@od.nih.gov NR 18 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 EI 1930-6180 J9 ILAR J JI ILAR J. PY 2014 VL 54 IS 3 BP 324 EP 328 DI 10.1093/ilar/ilt046 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA AC8CG UT WOS:000332760000009 PM 24615446 ER PT J AU Wang, YJ Chan, CC AF Wang, Yujuan Chan, Chi-Chao TI Gender Differences in Vogt-Koyanagi-Harada Disease and Sympathetic Ophthalmia SO JOURNAL OF OPHTHALMOLOGY LA English DT Review ID CHINESE HAN POPULATION; BEHCETS-DISEASE; VKH SYNDROME; NONINFECTIOUS UVEITIS; AUTOIMMUNE-DISEASES; GENE POLYMORPHISMS; PROGNOSTIC-FACTORS; LONG-TERM; PREGNANCY; ASSOCIATION AB Vogt-Koyanagi-Harada disease (VKH) and sympathetic ophthalmia (SO) are types of T-cell mediated autoimmune granulomatous uveitis. Although the two diseases share common clinical features, they have certain differences in gender predilections. VKH classically has been reported as more prevalent in females than males, yet some studies in Japan and China have not found differences in gender prevalence. Male patients have a higher risk of chorioretinal degeneration, vitiligo, and worse prognosis. Conversely, the changing levels of estrogen/progesterone during pregnancy and the menstrual cycle as well as higher levels of TGF-beta show a protective role in females. Potential causes of female predilection for VKH are associated with HLA-DR and HLA-DQ alleles. SO, a bilateral granulomatous uveitis, occurs in the context of one eye after a penetrating injury due to trauma or surgery. In contrast to the female dominance in VKH, males are more frequently affected by SO due to a higher incidence of ocular injury, especially during wartime. However, no gender predilection of SO has been reported in postsurgical cases. No clinically different manifestations are revealed between males and females in SO secondary to either ocular trauma or surgery. The potential causes of the gender difference may provide hints on future treatment and disease evaluation. C1 [Wang, Yujuan; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Wang, Yujuan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510060, Guangdong, Peoples R China. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov RI wang, yujuan/C-8428-2016 NR 81 TC 4 Z9 5 U1 1 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-004X EI 2090-0058 J9 J OPHTHALMOL JI J. Ophthalmol. PY 2014 AR 157803 DI 10.1155/2014/157803 PG 8 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA AC9NN UT WOS:000332861500001 ER PT J AU Vasconcelos, CO Coelho, ZCB Chaves, CD Teixeira, CR Pompeu, MML Teixeira, MJ AF Vasconcelos, Camila Oliveira Branco Coelho, Zirlane C. Chaves, Cristina de Souza Teixeira, Clarissa Romero Lima Pompeu, Margarida M. Teixeira, Maria Jania TI DISTINCT CELLULAR MIGRATION INDUCED BY Leishmania infantum chagasi AND SALIVA FROM Lutzomyia longipalpis IN A HEMORRHAGIC POOL MODEL SO REVISTA DO INSTITUTO DE MEDICINA TROPICAL DE SAO PAULO LA English DT Article DE L. infantum chagasi; Sand fly saliva; Leukocytes; Inflammation ID SAND FLY SALIVA; NEUTROPHIL GRANULOCYTES; PROMASTIGOTES; AMAZONENSIS; MODULATION; INFECTION; LIPOPHOSPHOGLYCAN; RECRUITMENT; MECHANISMS; EXPRESSION AB Recruitment of a specific cell population after Leishmania infection can influence the outcome of the disease. Cellular migration in response to Leishmania or vector saliva has been reported in air pouch model, however, cellular migration induced by Leishmania associated with host's blood and vector saliva in this model has not been described. Herein we investigated cellular migration into air pouch of hamster after stimulation with combination of L. chagasi and host's blood and Lutzomyia longipalpis saliva. Migration induced by saliva was 3-fold more than those induced by L. chagasi alone. Additionally, L. chagasi associated with blood and saliva induced significantly even more leukocytes into air pouch than Leishmania alone. L. chagasi recruited a diverse cell population; however, most of these cells seem to have not migrated to the inflammatory exudate, remaining in the pouch lining tissue. These results indicate that L. chagasi can reduce leukocyte accumulation to the initial site of infection, and when associated with vector saliva in the presence of blood components, increase the influx of more neutrophils than macrophages, suggesting that the parasite has developed a strategy to minimize the initial inflammatory response, allowing an unlimited progression within the host. This work reinforces the importance of studies on the salivary components of sand fly vectors of leishmaniasis in the transmission process and the establishment of the infection. C1 [Vasconcelos, Camila Oliveira; Branco Coelho, Zirlane C.; Chaves, Cristina de Souza; Lima Pompeu, Margarida M.; Teixeira, Maria Jania] Univ Fed Ceara, Fac Med, BR-60430160 Fortaleza, CE, Brazil. [Teixeira, Clarissa Romero] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Teixeira, MJ (reprint author), Univ Fed Ceara, Fac Med, Rua Alexandre Barauna 949, BR-60430160 Fortaleza, CE, Brazil. EM mjteixeira601@gmail.com FU Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazil FX This work received financial support from the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazil. NR 35 TC 2 Z9 2 U1 0 U2 4 PU INST MEDICINA TROPICAL SAO PAULO PI SAO PAULO PA AV DR ENEAS CARVALHO DE AGUIAR, 470, C CESAR, SAO PAULO, 05403-000, BRAZIL SN 0036-4665 EI 1678-9946 J9 REV INST MED TROP SP JI Rev. Inst. Med. Trop. Sao Paulo PD JAN-FEB PY 2014 VL 56 IS 1 BP 21 EP 27 DI 10.1590/S0036-46652014000100003 PG 7 WC Tropical Medicine SC Tropical Medicine GA AB6XI UT WOS:000331932400003 PM 24553604 ER PT J AU Liu, QR Rubio, FJ Bossert, JM Marchant, NJ Fanous, S Hou, XY Shaham, Y Hope, BT AF Liu, Qing-Rong Rubio, Francisco J. Bossert, Jennifer M. Marchant, Nathan J. Fanous, Sanya Hou, Xingyu Shaham, Yavin Hope, Bruce T. TI Detection of molecular alterations in methamphetamine-activated Fos-expressing neurons from a single rat dorsal striatum using fluorescence-activated cell sorting (FACS) SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE flow cytometry; gene expression; immediate early genes ID MEDIAL PREFRONTAL CORTEX; CONTEXT-SPECIFIC SENSITIZATION; INDUCED LOCOMOTOR-ACTIVITY; LASTING AP-1 COMPLEX; NUCLEUS-ACCUMBENS; DELTA-FOSB; ELECTROCONVULSIVE SEIZURE; INDUCED REINSTATEMENT; TRANSCRIPTION FACTOR; PROTEIN EXPRESSION AB Methamphetamine and other drugs activate a small proportion of all neurons in the brain. We previously developed a fluorescence-activated cell sorting (FACS)-based method to characterize molecular alterations induced selectively in activated neurons that express the neural activity marker Fos. However, this method requires pooling samples from many rats. We now describe a modified FACS-based method to characterize molecular alterations in Fos-expressing dorsal striatal neurons from a single rat using a multiplex pre-amplification strategy. Fos and NeuN (a neuronal marker) immunohistochemistry indicate that 5-6% of dorsal striatum neurons were activated 90 min after acute methamphetamine injections (5 mg/kg, i.p.) while less than 0.5% of neurons were activated by saline injections. We used FACS to separate NeuN-labeled neurons into Fos-positive and Fos-negative neurons and assessed mRNA expression using RT-qPCR from as little as five Fos-positive neurons. Methamphetamine induced 3-20-fold increases of immediate early genes arc, homer-2, c-fos, fosB, and its isoforms (Delta fosB and a novel isoform Delta fosB-2) in Fos-positive but not Fos-negative neurons. Immediate early gene mRNA induction was 10-fold lower or absent when assessed in unsorted samples from single dorsal striatum homogenates. Our modified method makes it feasible to study unique molecular alterations in neurons activated by drugs or drug-associated cues in complex addiction models. C1 [Liu, Qing-Rong; Rubio, Francisco J.; Bossert, Jennifer M.; Marchant, Nathan J.; Fanous, Sanya; Hou, Xingyu; Shaham, Yavin; Hope, Bruce T.] NIDA, Intramural Res Program, NIH, DHHS, Baltimore, MD 21224 USA. RP Liu, QR (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM qliu@intra.nida.nih.gov; bhope@intra.nida.nih.gov RI shaham, yavin/G-1306-2014; Hope, Bruce/A-9223-2010; Liu, Qing-Rong/A-3059-2012; OI Hope, Bruce/0000-0001-5804-7061; Liu, Qing-Rong/0000-0001-8477-6452; Marchant, Nathan/0000-0001-8269-0532 FU National Institute on Drug Abuse, Intramural Research Program; National Institutes of Health; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institute of Health [P30AR053503] FX This research was supported by the National Institute on Drug Abuse, Intramural Research Program. FJR was supported by an appointment to the NIDA Research Participation Program sponsored by the National Institutes of Health and administered by the Oak Ridge Institute for Science and Education and also by Becas-Chile Scholarship managed by CONICYT. QRL, YS, and BH designed the experiments, performed statistical analyses and wrote the manuscript; QRL, FJR, SF, JMB, NJM, and XH performed experiments. We thank Dr. Joe Chrest and Dr. Raffaello Cimbro for excellent technical assistance with FACS. The Johns Hopkins FACS Core facility was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institute of Health under Award Number P30AR053503. We also thank Thi N. Khuc for help in handling rats and Dr. Fabio Cruz for advice on flow cytometry analysis. The authors have no conflict of interests. NR 42 TC 13 Z9 13 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2014 VL 128 IS 1 BP 173 EP 185 DI 10.1111/jnc.12381 PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AA3FQ UT WOS:000330978700009 PM 23895375 ER PT J AU Berl, MM Zimmaro, LA Khan, OI Dustin, I Ritzl, E Duke, ES Sepeta, LN Sato, S Theodore, WH Gaillard, WD AF Berl, Madison M. Zimmaro, Lauren A. Khan, Omar I. Dustin, Irene Ritzl, Eva Duke, Elizabeth S. Sepeta, Leigh N. Sato, Susumu Theodore, William H. Gaillard, William D. TI Characterization of Atypical Language Activation Patterns in Focal Epilepsy SO ANNALS OF NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; COMPLEX PARTIAL EPILEPSY; FUNCTIONAL MRI; WADA TEST; BRAIN ACTIVATION; FMRI LANGUAGE; ELECTROCORTICAL STIMULATION; NORMAL-CHILDREN; SEIZURE FOCUS; LATERALIZATION AB Objective: Functional magnetic resonance imaging is sensitive to the variation in language network patterns. Large populations are needed to rigorously assess atypical patterns, which, even in neurological populations, are a minority. Methods: We studied 220 patients with focal epilepsy and 118 healthy volunteers who performed an auditory description decision task. We compared a data-driven hierarchical clustering approach to the commonly used a priori laterality index (LI) threshold (LI < 0.20 as atypical) to classify language patterns within frontal and temporal regions of interest. We explored (n = 128) whether IQ varied with different language activation patterns. Results: The rate of atypical language among healthy volunteers (2.5%) and patients (24.5%) agreed with previous studies; however, we found 6 patterns of atypical language: a symmetrically bilateral, 2 unilaterally crossed, and 3 right dominant patterns. There was high agreement between classification methods, yet the cluster analysis revealed novel correlations with clinical features. Beyond the established association of left-handedness, early seizure onset, and vascular pathology with atypical language, cluster analysis identified an association of handedness with frontal lateralization, early seizure onset with temporal lateralization, and left hemisphere focus with a unilateral right pattern. Intelligence quotient was not significantly different among patterns. Interpretation: Language dominance is a continuum; however, our results demonstrate meaningful thresholds in classifying laterality. Atypical language patterns are less frequent but more variable than typical language patterns, posing challenges for accurate presurgical planning. Language dominance should be assessed on a regional rather than hemispheric basis, and clinical characteristics should inform evaluation of atypical language dominance. Reorganization of language is not uniformly detrimental to language functioning. C1 [Berl, Madison M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Pediat Imaging & Tissue Sci Sect Tissue Biophys &, Bethesda, MD USA. [Berl, Madison M.; Zimmaro, Lauren A.; Duke, Elizabeth S.; Sepeta, Leigh N.; Gaillard, William D.] George Washington Univ, Childrens Natl Med Ctr, Neurosci Res Ctr, Washington, DC USA. [Zimmaro, Lauren A.; Khan, Omar I.; Dustin, Irene; Ritzl, Eva; Duke, Elizabeth S.; Sato, Susumu; Theodore, William H.; Gaillard, William D.] Natl Inst Neurol Disorders & Stroke, NIH, Clin Epilepsy Sect, Bethesda, MD USA. [Ritzl, Eva] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, Bldg 10,Room 7D-43,10 Ctr Dr,MSC 1408, Bethesda, MD 20892 USA. EM theodorw@ninds.nih.gov FU NIH National Institutes of Neurological Disorders and Stroke [1ZIANS002858-18, R01 NS44280, K23NS065121-01A2]; NIH National Center for Research Resources [M01RR020359]; Children's Research Institute; NINDS Clinical Epilepsy Section Division of Intramural Research; Intellectual and Developmental Disabilities Research Center; Children's National Medical Center [HD040677-07] FX This work was supported by the NIH National Institutes of Neurological Disorders and Stroke (1ZIANS002858-18, W. H. T.; R01 NS44280, W. D. G.; K23NS065121-01A2, M. M. B.); NIH National Center for Research Resources (M01RR020359); Children's Research Institute Avery Award (M. M. B.); NINDS Clinical Epilepsy Section Division of Intramural Research (W. H. T., W. D. G.); Intellectual and Developmental Disabilities Research Center; and Children's National Medical Center (HD040677-07). NR 62 TC 17 Z9 17 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2014 VL 75 IS 1 BP 33 EP 42 DI 10.1002/ana.24015 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AA3WQ UT WOS:000331026300005 PM 24038442 ER PT J AU De Fusco, M Vago, R Striano, P Di Bonaventura, C Zara, F Mei, D Kim, MS Muallem, S Chen, YJ Wang, Q Guerrini, R Casari, G AF De Fusco, Maurizio Vago, Riccardo Striano, Pasquale Di Bonaventura, Carlo Zara, Federico Mei, Davide Kim, Min Seuk Muallem, Shmuel Chen, Yunjia Wang, Qin Guerrini, Renzo Casari, Giorgio TI The alpha(2B)-Adrenergic Receptor Is Mutant in Cortical Myoclonus and Epilepsy SO ANNALS OF NEUROLOGY LA English DT Article ID PROTEIN-COUPLED-RECEPTORS; ALPHA-2 ADRENERGIC-RECEPTORS; SWISS-MODEL REPOSITORY; ALPHA(2)-ADRENERGIC RECEPTORS; CHROMOSOME 2P11.1-Q12.2; SPINOPHILIN; NEURONS; TREMOR; LOCUS; ADRENOCEPTORS AB Objective: Autosomal dominant cortical myoclonus and epilepsy (ADCME) is characterized by distal, fairly rhythmic myoclonus and epilepsy with variable severity. We have previously mapped the disease locus on chromosome 2p11.1-q12.2 by genome-wide linkage analysis. Additional pedigrees affected by similar forms of epilepsy have been associated with chromosomes 8q, 5p, and 3q, but none of the causing genes has been identified. We aim to identify the mutant gene responsible for this form of epilepsy. Methods: Genes included in the ADCME critical region were directly sequenced. Coimmunoprecipitation, immunofluorescent, and electrophysiologic approaches to transfected human cells have been utilized for testing the functional significance of the identified mutation. Results: Here we show that mutation in the alpha(2)-adrenergic receptor subtype B (alpha(2B)-AR) is associated with ADCME by identifying a novel in-frame insertion/deletion in 2 Italian families. The mutation alters several conserved residues of the third intracellular loop, hampering neither the alpha(2B)-AR plasma membrane localization nor the arrestin-mediated internalization capacity, but altering the binding with the scaffolding protein spinophilin upon neurotransmitter activation. Spinophilin, in turn, regulates interaction of G protein coupled receptors with regulator of G protein signaling proteins. Accordingly, the mutant alpha(2B)-AR increases the epinephrine-stimulated calcium signaling. Interpretation: The identified mutation is responsible for ADCME, as the loss of alpha(2B)-AR/spinophilin interaction causes a gain of function effect. This work implicates for the first time the alpha-adrenergic system in human epilepsy and opens new ways of understanding the molecular pathway of epileptogenesis, widening the spectrum of possible therapeutic targets. C1 [De Fusco, Maurizio; Vago, Riccardo; Casari, Giorgio] Univ Vita Salute San Raffaele, Milan, Italy. [De Fusco, Maurizio; Vago, Riccardo; Casari, Giorgio] Ist Sci San Raffaele, Ctr Translat Genom & Bioinformat, Milan, Italy. [Striano, Pasquale] Univ Genoa, Pediat Neurol & Muscular Dis Unit, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, G Gaslini Inst, Genoa, Italy. [Di Bonaventura, Carlo] Univ Roma La Sapienza, Dept Neurosci, Neurol Unit, Rome, Italy. [Zara, Federico] G Gaslini Inst Children, Neurogenet Lab, Dept Neurosci, Genoa, Italy. [Mei, Davide; Guerrini, Renzo] Anna Meyer Childrens Hosp, Pediat Neurol Unit & Labs, Florence, Italy. [Mei, Davide; Guerrini, Renzo] Univ Florence, Florence, Italy. [Kim, Min Seuk] Wonkwang Univ, Dept Oral Physiol, Sch Dent, Iksan, Jeonbuk, South Korea. [Muallem, Shmuel] Natl Inst Dent & Craniofacial Res, NIH, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, Bethesda, MD USA. [Chen, Yunjia; Wang, Qin] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL USA. [Guerrini, Renzo] Stella Maris, Pisa, Italy. RP Casari, G (reprint author), Univ Vita Salute San Raffaele, Sch Med, Neurogenom Unit, San Raffaele Sci Inst, Via Olgettina 58, I-20132 Milan, Italy. EM casari.giorgio@hsr.it OI CASARI, Giorgio/0000-0002-0115-8980 FU National Institutes of Health (NIH) [MH081917]; [RC2011] FX This work was supported by the Italian Minister of Health (grant RC2011 to R. G.) and by National Institutes of Health (NIH) grant MH081917 (Q. W.). We thank Drs M. R. Vannutelli and S. Anand for statistical assistance. NR 44 TC 11 Z9 13 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2014 VL 75 IS 1 BP 77 EP 87 DI 10.1002/ana.24028 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AA3WQ UT WOS:000331026300009 PM 24114805 ER PT J AU Qiu, CX Sigurdsson, S Zhang, Q Jonsdottir, MK Kjartansson, O Eiriksdottir, G Garcia, ME Harris, TB van Buchem, MA Gudnason, V Launer, LJ AF Qiu, Chengxuan Sigurdsson, Sigurdur Zhang, Qian Jonsdottir, Maria K. Kjartansson, Olafur Eiriksdottir, Gudny Garcia, Melissa E. Harris, Tamara B. van Buchem, Mark A. Gudnason, Vilmundur Launer, Lenore J. TI Diabetes, Markers of Brain Pathology and Cognitive Function: The Age, Gene/Environment Susceptibility-Reykjavik Study SO ANNALS OF NEUROLOGY LA English DT Article ID INFORMATION-PROCESSING SPEED; OLDER-ADULTS; NEUROPATHOLOGIC BASIS; CEREBRAL MICROBLEEDS; ALZHEIMERS-DISEASE; RISK-FACTORS; DEMENTIA; DECLINE; ATROPHY; MRI AB Objective: We investigated whether, and the extent to which, vascular and degenerative lesions in the brain mediate the association of diabetes with poor cognitive performance. Methods: This cross-sectional study included 4,206 participants (age>65 years; 57.8% women) of the Age, Gene/Environment Susceptibility-Reykjavik Study. Data were collected through interview, clinical examination, psychological testing, and laboratory tests. The composite scores on memory, information-processing speed, and executive function were derived from a cognitive test battery. Markers of cerebral macrovascular (cortical infarcts), microvascular (subcortical infarcts, cerebral microbleeds, and higher white matter lesion volume), and neurodegenerative (lower gray matter, normal white matter, and total brain tissue volumes) processes were assessed on magnetic resonance images. Mediation models were employed to test the mediating effect of brain lesions on the association of diabetes with cognitive performance controlling for potential confounders. Results: There were 462 (11.0%) persons with diabetes. Diabetes was significantly associated with lower scores on processing speed and executive function, but not with memory function. Diabetes was significantly associated with all markers of brain pathology. All of these markers were significantly associated with lower scores on memory, processing speed, and executive function. Formal mediation tests suggested that markers of cerebrovascular and degenerative pathology significantly mediated the associations of diabetes with processing speed and executive function. Interpretation: Diabetes is associated with poor performance on cognitive tests of information-processing speed and executive function. The association is largely mediated by markers of both neurodegeneration and cerebrovascular disease. Older people with diabetes should be monitored for cognitive problems and brain lesions. C1 [Qiu, Chengxuan; Zhang, Qian; Garcia, Melissa E.; Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA. [Qiu, Chengxuan] Stockholm Univ, Aging Res Ctr, Dept Neurobiol Care Sci & Soc, Karolinska Inst, S-10691 Stockholm, Sweden. [Sigurdsson, Sigurdur; Jonsdottir, Maria K.; Kjartansson, Olafur; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Jonsdottir, Maria K.] Univ Iceland, Fac Psychol, Reykjavik, Iceland. [Kjartansson, Olafur] Landspitali Univ Hosp, Dept Neurol, Reykjavik, Iceland. [Kjartansson, Olafur] Landspitali Univ Hosp, Dept Radiol, Reykjavik, Iceland. [van Buchem, Mark A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. [Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. RP Launer, LJ (reprint author), NIA, Lab Epidemiol & Populat Sci, NIH, 7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov RI Gudnason, Vilmundur/K-6885-2015; OI Gudnason, Vilmundur/0000-0001-5696-0084; Qiu, Chengxuan/0000-0003-1922-4912 FU NIH/National Institute on Aging (NIA) [N01-AG-12100]; NIA, USA; Icelandic Heart Association; Icelandic Parliament, Iceland; Swedish Research Council; Karolinska Institutet, Stockholm, Sweden FX The AGES-Reykjavik Study was funded by NIH/National Institute on Aging (NIA) contract N01-AG-12100 and the Intramural Research Program of the NIA, USA and by the Icelandic Heart Association and the Icelandic Parliament, Iceland. C. Q. is supported by grants from the Swedish Research Council and Karolinska Institutet, Stockholm, Sweden. The funding sources had no role in the study design; in data collection, analysis, and interpretation; in writing of the report; or in the decision to submit the report for publication. NR 42 TC 33 Z9 34 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2014 VL 75 IS 1 BP 138 EP 146 DI 10.1002/ana.24063 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AA3WQ UT WOS:000331026300015 PM 24243491 ER PT J AU Sztalryd, C Kimmel, AR AF Sztalryd, Carole Kimmel, Alan R. TI Perilipins: Lipid droplet coat proteins adapted for tissue-specific energy storage and utilization, and lipid cytoprotection SO BIOCHIMIE LA English DT Review DE Cytosolic lipid droplets; Ectopic fat; Metabolic disease; Lipotoxicity; Energy homeostasis ID HORMONE-SENSITIVE LIPASE; DIFFERENTIATION-RELATED PROTEIN; ADIPOSE TRIGLYCERIDE LIPASE; DIET-INDUCED OBESITY; INSULIN-RESISTANCE; FATTY LIVER; STIMULATED LIPOLYSIS; ADIPOCYTE LIPOLYSIS; 3T3-L1 ADIPOCYTES; DOWN-REGULATION AB Cytosolic lipid storage droplets are primary functional organelles that regulate cellular lipid metabolism and homeostasis. Paradoxically, excess lipid stores are linked to both adaptive (fasting and chronic exercise) and mal-adaptive (obesity and related health complications) conditions. Thus, collective metabolic and physiological processes must balance lipid storage and utilization with prevention of lipocytotoxicity and compounding tissue dysfunctions, urging the need to further define the connection of mammalian lipid droplet function and lipid homeostasis. The perilipins are a multi-protein family that targets lipid droplet surfaces and regulates lipid storage and hydrolysis. Study of perilipin functions has provided insight into the physiological roles of cytosolic lipid droplets and their relationship with obesity-related pathologies. Here, we review the current knowledge of the multiple perilipin proteins in regulating tissue-specific lipid droplets and associations with tissue and systemic energetics. Published by Elsevier Masson SAS. C1 [Sztalryd, Carole] Baltimore Vet Affairs Hlth Care Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD 21201 USA. [Sztalryd, Carole] Univ Maryland, Sch Med, Dept Med, Div Endocrinol, Baltimore, MD 21201 USA. [Kimmel, Alan R.] NIDDK, Lab Cellular & Dev Biol 50 3351, NIH, Bethesda, MD 20892 USA. RP Sztalryd, C (reprint author), Div Endocrinol, HH Room 445A,650 West Redwwod St, Baltimore, MD 21201 USA. EM csztalry@grecc.umaryland.edu FU Intramural Research Program of the National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases; American Diabetes Association [1-05-CD-17]; American Heart Association [11 GRNT7600027]; Geriatric Research, Education and Clinical Center, Baltimore Veterans Affairs Health Care Center; Clinical Nutrition Research Unit of Maryland [DK072488] FX This research was supported by the Intramural Research Program of the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases (A.R.K.), career development award 1-05-CD-17 from the American Diabetes Association (to C.S.), a grant from NIH 1R01 DK 075017 (to C.S.), grant in aid 11 GRNT7600027 from the American Heart Association (to C.S.), and the Geriatric Research, Education and Clinical Center, Baltimore Veterans Affairs Health Care Center, the Clinical Nutrition Research Unit of Maryland (DK072488). NR 85 TC 39 Z9 43 U1 1 U2 20 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0300-9084 EI 1638-6183 J9 BIOCHIMIE JI Biochimie PD JAN PY 2014 VL 96 BP 96 EP 101 DI 10.1016/j.biochi.2013.08.026 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AB8OA UT WOS:000332048700013 PM 24036367 ER PT J AU Roche, VP Mohamad-Djafari, A Innominato, PF Karaboue, A Gorbach, A Levi, FA AF Roche, Veronique Pasquale Mohamad-Djafari, Ali Innominato, Pasquale Fabio Karaboue, Abdoulaye Gorbach, Alexander Levi, Francis Albert TI Thoracic surface temperature rhythms as circadian biomarkers for cancer chronotherapy SO CHRONOBIOLOGY INTERNATIONAL LA English DT Article DE Chronotherapy; circadian biomarkers; colorectal cancer; rest-activity; skin temperature ID METASTATIC COLORECTAL-CANCER; DIURNAL CORTISOL RHYTHM; QUALITY-OF-LIFE; SUPRACHIASMATIC NUCLEUS; TUMOR PROGRESSION; BODY-TEMPERATURE; SURVIVAL; MICE; CLOCK; TRANSCRIPTION AB The disruption of the temperature circadian rhythm has been associated with cancer progression, while its amplification resulted in cancer inhibition in experimental tumor models. The current study investigated the relevance of skin surface temperature rhythms as biomarkers of the Circadian Timing System (CTS) in order to optimize chronotherapy timing in individual cancer patients. Baseline skin surface temperature at four sites and wrist accelerations were measured every minute for 4 days in 16 patients with metastatic gastro-intestinal cancer before chronotherapy administration. Temperature and rest-activity were recorded, respectively, with wireless skin surface temperature patches (Respironics, Phillips) and an actigraph (Ambulatory Monitoring). Both variables were further monitored in 10 of these patients during and after a 4-day course of a fixed chronotherapy protocol. Collected at baseline, during and after therapy longitudinal data sets were processed using Fast Fourier Transform Cosinor and Linear Discriminant Analyses methods. A circadian rhythm was statistically validated with a period of 24 h (p<0.05) for 49/61 temperature time series (80.3%), and 15/16 rest-activity patterns (93.7%) at baseline. However, individual circadian amplitudes varied from 0.04 degrees C to 2.86 degrees C for skin surface temperature (median, 0.72 degrees C), and from 16.6 to 146.1 acc/min for rest-activity (median, 88.9 acc/min). Thirty-nine pairs of baseline temperature and rest-activity time series (75%) were correlated (r>vertical bar 0.7 vertical bar; p<0.05). Individual circadian acrophases at baseline were scattered from 15: 18 to 6: 05 for skin surface temperature, and from 12: 19 to 15: 18 for rest-activity, with respective median values of 01: 10 (25-75% quartiles, 22: 35-3: 07) and 14: 12 (13: 14-14: 31). The circadian patterns in skin surface temperature and rest-activity persisted or were amplified during and after fixed chronotherapy delivery for 5/10 patients. In contrast, transient or sustained disruption of these biomarkers was found for the five other patients, as indicated by the lack of any statistically significant dominant period in the circadian range. No consistent correlation (r= 0.05) was found between paired rest-activity and temperature time series during fixed chronotherapy delivery. In conclusion, large inter-patient differences in circadian amplitudes and acrophases of skin surface temperature were demonstrated for the first time in cancer patients, despite rather similar rest-activity acrophases. The patient-dependent coupling between both CTS biomarkers, and its possible alteration on a fixed chronotherapy protocol, support the concept of personalized cancer chronotherapy. C1 [Roche, Veronique Pasquale; Innominato, Pasquale Fabio; Karaboue, Abdoulaye; Levi, Francis Albert] INSERM, U776, Villejuif, France. [Roche, Veronique Pasquale; Gorbach, Alexander] NIBIB, Infrared Imaging & Thermometry Unit, NIH, Bethesda, MD USA. [Roche, Veronique Pasquale; Innominato, Pasquale Fabio; Levi, Francis Albert] Paris South Univ, UMR S0776, Orsay, France. [Mohamad-Djafari, Ali] Univ Paris 11, Signaux & Syst Lab, Gif Sur Yvette, France. [Innominato, Pasquale Fabio; Levi, Francis Albert] Hop Paul Brousse, AP HP, Chronotherapy Unit, Dept Med Oncol, Villejuif, France. RP Levi, FA (reprint author), INSERM, U776, Villejuif, France. EM francis.levi@inserm.fr OI Roche, Veronique/0000-0001-8064-0507 FU ARTBC International; Braun France FX The authors report no conflicts of interest. Support for this project was provided by ARTBC International and Braun France. NR 53 TC 9 Z9 9 U1 0 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0742-0528 EI 1525-6073 J9 CHRONOBIOL INT JI Chronobiol. Int. PY 2014 VL 31 IS 3 BP 409 EP 420 DI 10.3109/07420528.2013.864301 PG 12 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA AB9NV UT WOS:000332122200013 PM 24397341 ER PT J AU Krizanova, O Markova, J Pacak, K Skultety, L Soltysova, A Hudecova, S AF Krizanova, Olga Markova, Jana Pacak, Karel Skultety, Ludovit Soltysova, Andrea Hudecova, Sona TI Triptolide induces apoptosis through the SERCA 3 upregulation in PC12 cells SO GENERAL PHYSIOLOGY AND BIOPHYSICS LA English DT Article DE Triptolide; Calcium transport; SERCA 3; Apoptosis ID FACTOR-KAPPA-B; CALCIUM PUMPS; CANCER; PHEOCHROMOCYTOMA; NEUROBLASTOMA; THAPSIGARGIN; PROGRESSION; METASTASIS; INHIBITION; EXPRESSION AB Diterpenoid triepoxide - Triptolide (TTL) - increased protein levels of the noradrenaline transporter in three pheochromocytoma cell lines. This transporter is involved in the apoptosis induction through the inhibition of a transcription factor NF-kappa B. Nevertheless, calcium release from the endoplasmic reticulum can also induce inner, mitochondrial pathway of apoptosis in variety of cells. Therefore, the aim of this work was to evaluate an involvement of calcium and, more specifically, intracellular calcium transport systems in the apoptosis induction in pheochrocytoma cell line PC12. We observed significantly increased amount of reticular calcium in TTL-treated cells compared to control, untreated cells. Surprisingly, gene expression of the IP3 receptors was not changed after the TTL treatment, but ryanodine receptor of the type 2 (RyR2) was downregulated and sarco/endoplasmic reticulum calcium ATPase type 3 (SERCA 3) was upregulated in TTL- treated cells, compared to untreated controls. SERCA 3 blocking with the specific blocker thapsigargin prevented increase in apoptosis observed by the TTL treatment. Decrease in the ATP production by a replacement of glucose in the cultivation medium for its non-utilizable analog 2-deoxyglucose also prevented induction of the apoptosis in TTL-treated PC12 cells. Thus, these results suggest that upregulation of the SERCA 3 is ultimately involved in the TTL-induced apoptosis in PC12 cells. C1 [Krizanova, Olga; Markova, Jana; Soltysova, Andrea; Hudecova, Sona] Slovak Acad Sci, Inst Mol Physiol & Genet, Ctr Excellence Studying Metab Aspects Dev Diagnos, Bratislava 83334, Slovakia. [Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Skultety, Ludovit] Slovak Acad Sci, Inst Virol, Bratislava 83334, Slovakia. RP Hudecova, S (reprint author), Slovak Acad Sci, Inst Mol Physiol & Genet, Vlarska 5, Bratislava 83334, Slovakia. EM sona.hudecova@savba.sk RI Skultety, Ludovit/N-2160-2014 FU Research & Development Operational Programme; ERDF; [VEGA 0074/13]; [APVV-0045-11]; [KC: ITMS 26240220071] FX This work was supported by grants VEGA 0074/13, APVV-0045-11, Project implementation: KC: ITMS 26240220071, supported by the Research & Development Operational Programme funded by the ERDF. Authors wish to thank to Dr. Danchenko for the help with MIBG determination. NR 27 TC 4 Z9 4 U1 0 U2 13 PU GENERAL PHYSIOL AND BIOPHYSICS PI BRATISLAVA PA INST OF MOLEC PHYSIOL GENETICS SLOVAK ACAD OF SCI VLARSKA 5, 83334 BRATISLAVA, SLOVAKIA SN 0231-5882 EI 1338-4325 J9 GEN PHYSIOL BIOPHYS JI Gen. Physiol. Biophys. PY 2014 VL 33 IS 1 BP 137 EP 144 DI 10.4149/gpb_2014004 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Physiology SC Biochemistry & Molecular Biology; Biophysics; Physiology GA AC0MQ UT WOS:000332189800014 PM 24448368 ER PT J AU Engel, OG AF Engel, Odile Gabay TI Reply to the comment by Wendling et al. on the article "Sirt1-deficient mice exhibit an altered cartilage phenotype", Joint Bone Spine 2013;80:613-20 SO JOINT BONE SPINE LA English DT Letter DE OA; Arthritis; Epigenetic control; Sirtuins ID SIRT1 PROTECTS; CHONDROCYTES; OSTEOARTHRITIS C1 NIAMS, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Engel, OG (reprint author), NIAMS, Immunoregulat Sect, Autoimmun Branch, NIH, 10 Ctr Dr,B10 R13C120, Bethesda, MD 20892 USA. EM odile.gabay@yahoo.com NR 18 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 1297-319X EI 1778-7254 J9 JOINT BONE SPINE JI Joint Bone Spine PD JAN PY 2014 VL 81 IS 1 BP 104 EP 105 DI 10.1016/j.jbspin.2013.11.004 PG 3 WC Rheumatology SC Rheumatology GA AB4XM UT WOS:000331793300030 PM 24365198 ER PT J AU Knoben, JE Phillips, SJ AF Knoben, James E. Phillips, Steven J. TI New drug information resources for pharmacists at the National Library of Medicine SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION LA English DT Article DE Drug information; evidence based; hepatotoxicity; lactation; package inserts; search portal; structured product labeling AB Objective: To provide an overview of selected drug information-related data-bases of the National Library of Medicine (NLM), with a focus on newer resources that support the professional information needs of pharmacists and other health care providers. Summary: NLM, which is the world's largest medical library, provides an array of bibliographic, factual, and evidence-based drug, herbal remedy, and dietary supplement information resources. Five of the more recently introduced online resources include areas of particular importance to pharmacists, including a repository of current product labeling/package inserts, with automated search links to associated information resources; a portal to drug information that allows pharmacists to search multiple databases simultaneously and link to related medication and health care information resources; authoritative information on the effects of medications, herbal remedies, and dietary supplements in nursing infants and their mothers; comprehensive information, including a case registry, on the potential for liver toxicity due to drugs, herbal remedies, and dietary supplements; and a pill identification system with two intuitive search methodologies. Conclusion: NLM provides several clinical-scientific drug information resources that are particularly useful in meeting the professional information needs of pharmacists. C1 [Knoben, James E.] NIH, Specialized Informat Serv Div, Bethesda, MD 20892 USA. [Phillips, Steven J.] NIH, Natl Lib Med, Specialized Informat Serv Div, Bethesda, MD 20892 USA. RP Knoben, JE (reprint author), Natl Lib Med, 6707 Democracy Blvd,Suite 510, Bethesda, MD 20892 USA. EM james.knoben@nih.hhs.gov NR 8 TC 0 Z9 0 U1 0 U2 1 PU AMER PHARMACEUTICAL ASSOC PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 1544-3191 EI 1544-3450 J9 J AM PHARM ASSOC JI J. Am. Pharm. Assoc. PD JAN-FEB PY 2014 VL 54 IS 1 BP 49 EP 55 DI 10.1331/JAPhA.2014.13123 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB8IL UT WOS:000332033500013 PM 24362595 ER PT J AU Margarucci, L Monti, MC Esposito, R Tosco, A Hamel, E Riccio, R Casapullo, A AF Margarucci, Luigi Monti, Maria Chiara Esposito, Roberta Tosco, Alessandra Hamel, Ernest Riccio, Raffaele Casapullo, Agostino TI N-Formyl-7-amino-11-cycloamphilectene, a marine sponge metabolite, binds to tubulin and modulates microtubule depolymerization SO MOLECULAR BIOSYSTEMS LA English DT Article ID NATURAL-PRODUCTS; KINASE INHIBITORS; PROTEIN; TARGETS; SESTERTERPENE; DRUGS AB The importance of protein-small molecule interaction in drug discovery, medicinal chemistry and biology has driven the development of new analytical methods to disclose the whole interactome of bioactive compounds. To accelerate targets discovery of N-formyl-7-amino-11-cycloamphilectene (CALe), a marine bioactive diterpene isolated from the Vanuatu sponge Axinella sp., a chemoproteomic-based approach has been successfully developed. CALe is a potent anti-inflammatory agent, modulating NO and prostaglandin E2 overproduction by dual inhibition of the enhanced inducible NO synthase expression and cyclo-oxygenase-2 activity, without any evidence of cytotoxic effects. In this paper, several isoforms of tubulin have been identified as CALe off-targets by chemical proteomics combined with bio-physical orthogonal approaches. In the following biological analysis of its cellular effect, CALe was found to protect microtubules against the colcemid depolymerizing effect. C1 [Margarucci, Luigi; Monti, Maria Chiara; Esposito, Roberta; Tosco, Alessandra; Riccio, Raffaele; Casapullo, Agostino] Univ Salerno, Dipartimento Farm, I-84084 Fisciano, Italy. [Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA. RP Casapullo, A (reprint author), Univ Salerno, Dipartimento Farm, Via Giovanni Paolo 2 132, I-84084 Fisciano, Italy. EM casapullo@unisa.it RI Tosco, Alessandra/F-6773-2011; Riccio, Raffaele/A-3405-2008 OI Riccio, Raffaele/0000-0001-5073-5513 FU University of Salerno; Regione Campania (Italy) through POR funds FX Financial support by the University of Salerno is gratefully acknowledged. The authors also acknowledge the use of the instrumental facilities of the Centre of Competence in Diagnostics and Molecular Pharmaceutics supported by Regione Campania (Italy) through POR funds. NR 28 TC 0 Z9 0 U1 1 U2 15 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X EI 1742-2051 J9 MOL BIOSYST JI Mol. Biosyst. PY 2014 VL 10 IS 4 BP 862 EP 867 DI 10.1039/c3mb70315k PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AC3XZ UT WOS:000332456200017 PM 24493364 ER PT J AU Jasinska, AJ Stein, EA Kaiser, J Naumer, MJ Yalachkov, Y AF Jasinska, Agnes J. Stein, Elliot A. Kaiser, Jochen Naumer, Marcus J. Yalachkov, Yavor TI Factors modulating neural reactivity to drug cues in addiction: A survey of human neuroimaging studies SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Addiction; Drug abuse; Cue reactivity; Functional magnetic resonance imaging (fMRI); Positron emission tomography (PET); Modulation; Craving; Addiction severity; Treatment success; Withdrawal; Regulation; Sensory modality; Treatment status; Stress; Drug availability ID COCAINE-SEEKING BEHAVIOR; NUCLEUS-ACCUMBENS CORE; ALCOHOL-USE DISORDER; NICOTINIC ACETYLCHOLINE-RECEPTOR; BRAIN ACTIVATION PATTERNS; SMOKING CUES; CIGARETTE SMOKERS; DORSAL STRIATUM; ATTENTIONAL BIAS; ORBITOFRONTAL CORTEX AB Human neuroimaging studies suggest that neural cue reactivity is strongly associated with indices of drug use, including addiction severity and treatment success. However, little is known about factors that modulate cue reactivity. The goal of this review, in which we survey published fMRI and PET studies on drug cue reactivity in cocaine, alcohol, and tobacco cigarette users, is to highlight major factors that modulate brain reactivity to drug cues. First, we describe cue reactivity paradigms used in neuroimaging research and outline the brain circuits that underlie cue reactivity. We then discuss major factors that have been shown to modulate cue reactivity and review specific evidence as well as outstanding questions related to each factor. Building on previous model-building reviews on the topic, we then outline a simplified model that includes the key modulatory factors and a tentative ranking of their relative impact. We conclude with a discussion of outstanding challenges and future research directions, which can inform future neuroimaging studies as well as the design of treatment and prevention programs. Published by Elsevier Ltd. C1 [Jasinska, Agnes J.; Stein, Elliot A.] Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. [Kaiser, Jochen; Naumer, Marcus J.; Yalachkov, Yavor] Goethe Univ, Inst Med Psychol, Frankfurt, Germany. RP Jasinska, AJ (reprint author), Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. EM jasinskaaj@mail.nih.gov; yalachkov@med.uni-frankfurt.de FU National Institute on Drug Abuse Intramural Research Program (NIDA-IRP); Hessisches Ministerium fur Wissenschaft und Kultur (LOEWE Forschungsschwerpunkt Neuronale Koordination Frankfurt) FX A.J.J. and E.A.S. are supported by the National Institute on Drug Abuse Intramural Research Program (NIDA-IRP). M.J.N., J.K. and Y.Y. are supported by the Hessisches Ministerium fur Wissenschaft und Kultur (LOEWE Forschungsschwerpunkt Neuronale Koordination Frankfurt). NR 155 TC 77 Z9 79 U1 8 U2 73 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 EI 1873-7528 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD JAN PY 2014 VL 38 BP 1 EP 16 DI 10.1016/j.neubiorev.2013.10.013 PG 16 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AB4QM UT WOS:000331775000001 PM 24211373 ER PT J AU Kiblawi, ZN Smith, LM Diaz, SD LaGasse, LL Derauf, C Newman, E Shah, R Arria, A Huestis, M Haning, W Strauss, A DellaGrotta, S Dansereau, LM Neal, C Lester, B AF Kiblawi, Zeina N. Smith, Lynne M. Diaz, Sabrina D. LaGasse, Linda L. Derauf, Chris Newman, Elana Shah, Rizwan Arria, Amelia Huestis, Marilyn Haning, William Strauss, Arthur DellaGrotta, Sheri Dansereau, Lynne M. Neal, Charles Lester, Barry TI Prenatal Methamphetamine Exposure and Neonatal and Infant Neurobehavioral Outcome: Results from the IDEAL Study SO SUBSTANCE ABUSE LA English DT Article DE stress; child development; Amphetamine; newborn; arousal ID MATERNAL LIFE-STYLE; CHILD-ABUSE; NEWBORN NEUROBEHAVIOR; SUBSTANCE EXPOSURE; DRUG EXPOSURE; PREGNANCY; ALCOHOL; SMOKING; AMPHETAMINE; ENVIRONMENT AB Background: Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. How MA use during pregnancy affects neonatal and infant neurobehavior is unknown. Methods: The Infant Development, Environment, and Lifestyle (IDEAL) study screened 34,833 subjects at 4 clinical centers. Of the subjects, 17,961 were eligible and 3705 were consented, among which 412 were enrolled for longitudinal follow-up. Exposed subjects were identified by self-report and/or gas chromatography/mass spectroscopy (GC/MS) confirmation of amphetamine and metabolites in meconium. Comparison subjects were matched (race, birth weight, maternal education, insurance), denied amphetamine use, and had a negative meconium screen. Both groups included prenatal alcohol, tobacco, and marijuana use, but excluded use of opiates, lysergic acid diethylamide, or phencyclidine. The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) was administered within the first 5days of life and again at 1 month to 380 enrollees (185 exposed, 195 comparison). Analysis of variance (ANOVA) tested exposure effects on NNNS summary scores at birth and 1 month. General linear model (GLM) repeated-measures analysis assessed the effect of MA exposure over time on the NNNS scores with and without covariates. Results: By 1 month of age, both groups demonstrated higher quality of movement (P = .029), less lethargy (P = .001), and fewer asymmetric reflexes (P = .012), with no significant differences in NNNS scores between the exposed and comparison groups. Over the first month of life, arousal increased in exposed infants but decreased in comparison infants (P = .031) and total stress was decreased in exposed infants, with no change in comparison infants (P=.026). Conclusions: Improvement in total stress and arousal were observed in MA-exposed newborns by 1 month of age relative to the newborn period. C1 [Kiblawi, Zeina N.; Smith, Lynne M.; Diaz, Sabrina D.] Harbor UCLA Med Ctr, LA Biomed Inst, Los Angeles, CA USA. [Kiblawi, Zeina N.; Smith, Lynne M.; Diaz, Sabrina D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [LaGasse, Linda L.; DellaGrotta, Sheri; Dansereau, Lynne M.; Lester, Barry] Brown Univ, Women & Infants Hosp, Warren Alpert Med Sch, Ctr Study Children Risk, Providence, RI USA. [Derauf, Chris; Haning, William; Neal, Charles] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA. [Shah, Rizwan] Blank Hosp Reg Child Protect Ctr Iowa Hlth, Des Moines, IA USA. [Arria, Amelia] Univ Maryland, Sch Publ Hlth, Ctr Young Adult Hlth & Dev, College Pk, MD 20742 USA. [Huestis, Marilyn] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [Strauss, Arthur] MCHLB, Long Beach, CA USA. RP Smith, LM (reprint author), Harbor UCLA Med Ctr, Los Angeles Biomed Inst, 1124 West Carson St,Box 446, Torrance, CA 90502 USA. EM smith@labiomed.org OI Arria, Amelia/0000-0002-6360-9265 FU NIDA [1RO1DA014948]; National Center on Research Resources [1UL1-RR033176, P20 RR11091] FX This study was supported by NIDA grant 1RO1DA014948 and in part by the National Center on Research Resources, 1UL1-RR033176 and P20 RR11091. NR 42 TC 4 Z9 4 U1 3 U2 31 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PD JAN 1 PY 2014 VL 35 IS 1 BP 68 EP 73 DI 10.1080/08897077.2013.814614 PG 6 WC Substance Abuse SC Substance Abuse GA AB9WM UT WOS:000332146400012 PM 24588296 ER PT J AU Kelly, AL Raffel, SJ Fischer, R Bellinghausen, M Stevenson, C Schwan, TG AF Kelly, Ashley L. Raffel, Sandra J. Fischer, Roberti Bellinghausen, Michael Stevenson, Connie Schwan, Tom G. TI First isolation of the relapsing fever spirochete, Borrelia herrnsii, from a domestic dog SO TICKS AND TICK-BORNE DISEASES LA English DT Article DE Canine borreliosis; Ornithodoros hermsi; Argasid ticks; Veterinary pathogens; Relapsing fever ID NORTH-AMERICA; LYME-DISEASE; HERMSII; CALIFORNIA; BURGDORFERI; INFECTIONS; TURICATAE; FLORIDA; TEXAS; USA AB In North America, tick-borne relapsing fever of humans is most frequently caused by infection with the spirochete Borrelia hermsii. Prior to our investigation, this spirochete was not known to infect dogs although another species, Borrelia turicatae, has been isolated from domestic canids in Florida and Texas. A clinically ill dog in Washington, USA, was spirochetemic upon examination. Spirochetes were isolated from the dog's serum and examined by PCR and multi-locus sequence typing. DNA sequences for 7 loci all typed the spirochete as B. hermsii and a member of genomic group II of this species. Therefore, companion dogs that reside in rustic cabins in higher elevation forests are at risk of infection with B. hermsii. Published by Elsevier GmbH. C1 [Kelly, Ashley L.; Raffel, Sandra J.; Fischer, Roberti; Schwan, Tom G.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Bellinghausen, Michael] Kenmore Vet Hosp, Kenmore, WA USA. [Stevenson, Connie] Phoenix Cent Labs Veterinarians, Mukilteo, WA USA. RP Schwan, TG (reprint author), NIAID, Rocky Mt Labs, NIH, 903 South 4th St, Hamilton, MT 59840 USA. EM tschwan@niaid.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. NR 34 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 1877-959X EI 1877-9603 J9 TICKS TICK-BORNE DIS JI Ticks Tick-Borne Dis. PY 2014 VL 5 IS 2 BP 95 EP 99 DI 10.1016/j.ttbdis.2013.08.005 PG 5 WC Infectious Diseases; Microbiology; Parasitology SC Infectious Diseases; Microbiology; Parasitology GA AB8RN UT WOS:000332057800003 PM 24252262 ER PT J AU Glatz, M Muellegger, RR Maurer, F Fingerle, V Achermann, Y Wilske, B Bloemberg, GV AF Glatz, Martin Muellegger, Robert R. Maurer, Florian Fingerle, Volker Achermann, Yvonne Wilske, Bettina Bloemberg, Guido V. TI Detection of Candidatus Neoehrlichia mikurensis, Borrelia burgdorferi sensu lato genospecies and Anaplasma phagocytophilum in a tick population from Austria SO TICKS AND TICK-BORNE DISEASES LA English DT Article DE Tick-borne disease; Borrelia burgdorferi; Anaplasma phagocytophilum; Candidatus Neoehrlichia mikurensis; Ixodes ricinus ID IXODES-RICINUS TICKS; HUMAN GRANULOCYTIC ANAPLASMOSIS; BORNE PATHOGENS; MOLECULAR-DETECTION; EHRLICHIA; INFECTION; EUROPE; IDENTIFICATION; COINFECTION; ANIMALS AB Candidatus Neoehrlichia mikurensis DNA was discovered in Ixodes ricinus ticks in 1999 and is referred to as an emerging human pathogen since its first detection in patients with febrile illness reported in 2010. In recent years, Ca. Neoehrlichia mikurensis has been detected in ticks from several European, Asian, and African countries. However, no epidemiological data exist for Austria, which is a highly endemic region for tick-transmitted diseases. To assess the geographic spread and prevalence of Ca. Neoehrlichia mikurensis sympatric with other tick-transmitted pathogens, we analysed 518 I. ricinus ticks collected in 2002 and 2003 in Graz, Austria. The prevalence of Ca. Neoehrlichia mikurensis was 4.2%, that of Borrelia burgdorferi sensu lato 25.7%, and that of Anaplasma phagocytophilum 1%. Coinfections with Ca. Neoehrlichia mikurensis and B. burgdorferi sensu lato were found in 2.3% of all ticks. Thus, the results show a relatively high prevalence of Ca. Neoehrlichia mikurensis in Austrian ticks suggesting a high probability for the occurrence of undiagnosed human infections in Austria. (C) 2013 Elsevier GmbH. All rights reserved. C1 [Glatz, Martin; Muellegger, Robert R.] Med Univ Graz, Dept Dermatol, Graz, Austria. [Glatz, Martin] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Muellegger, Robert R.] State Hosp Wiener Neustadt, Dept Dermatol, Wiener Neustadt, Austria. [Maurer, Florian; Bloemberg, Guido V.] Univ Zurich, Inst Med Microbiol, Zurich, Switzerland. [Fingerle, Volker] Bavarian Hlth & Food Safety Author, German Natl Reference Ctr Borrelia, Oberschleissheim, Germany. [Achermann, Yvonne] Univ & Univ Hosp Zurich, Div Infect Dis, Zurich, Switzerland. [Achermann, Yvonne] Univ & Univ Hosp Zurich, Hosp Epidemiol, Zurich, Switzerland. [Wilske, Bettina] Univ Munich, Max von Pettenkofer Inst, Munich, Germany. RP Glatz, M (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10-12N260,10 Ctr Dr, Bethesda, MD 20892 USA. EM glatz.martin@gmx.net RI Maurer, Florian/J-9687-2014; Infektiologie, USZ/A-6921-2011; OI Maurer, Florian/0000-0001-8353-5964; Fingerle, Volker/0000-0002-3835-5646 NR 45 TC 12 Z9 12 U1 1 U2 14 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 1877-959X EI 1877-9603 J9 TICKS TICK-BORNE DIS JI Ticks Tick-Borne Dis. PY 2014 VL 5 IS 2 BP 139 EP 144 DI 10.1016/j.ttbdis.2013.10.006 PG 6 WC Infectious Diseases; Microbiology; Parasitology SC Infectious Diseases; Microbiology; Parasitology GA AB8RN UT WOS:000332057800011 PM 24345313 ER PT S AU Schiller, JT Lowy, DR AF Schiller, John T. Lowy, Douglas R. BE Chang, MH Jeang, KT TI Virus Infection and Human Cancer: An Overview SO VIRUSES AND HUMAN CANCER: FROM BASIC SCIENCE TO CLINICAL PREVENTION SE Recent Results in Cancer Research LA English DT Article; Book Chapter ID MERKEL CELL-CARCINOMA; HEPATITIS-C VIRUS; HUMAN-PAPILLOMAVIRUS; HEPATOCELLULAR-CARCINOMA; VIRAL-HEPATITIS; HPV VACCINATION; KAPOSIS-SARCOMA; CERVICAL-CANCER; UNITED-STATES; HERPESVIRUS AB It is now estimated that approximately 10 % of worldwide cancers are attributable to viral infection, with the vast majority (>85 %) occurring in the developing world. Oncogenic viruses include various classes of DNA and RNA viruses and induce cancer by a variety of mechanisms. A unifying theme is that cancer develops in a minority of infected individuals and only after chronic infection of many years duration. The viruses associated with the greatest number of cancer cases are the human papillomaviruses (HPVs), which cause cervical cancer and several other epithelial malignancies, and the hepatitis viruses HBV and HCV, which are responsible for the majority of hepatocellular cancer. Other oncoviruses include Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpes virus (KSHV), human T-cell leukemia virus (HTLV-I), and Merkel cell polyomavirus (MCPyV). Identification of the infectious cause has led to several interventions that may reduce the risk of developing these tumors. These include preventive vaccines against HBV and HPV, HPV-based testing for cervical cancer screening, anti-virals for the treatment of chronic HBV and HCV infection, and screening the blood supply for the presence of HBV and HCV. Successful efforts to identify additional oncogenic viruses in human cancer may lead to further insight into etiology and pathogenesis as well as to new approaches for therapeutic and prophylactic intervention. C1 [Schiller, John T.; Lowy, Douglas R.] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM schillej@mail.nih.gov; dl60z@nih.gov NR 48 TC 11 Z9 13 U1 1 U2 79 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 978-3-642-38965-8; 978-3-642-38964-1 J9 RECENT RESULTS CANC JI Rec. Res. Camcer Res. PY 2014 VL 193 BP 1 EP 10 DI 10.1007/978-3-642-38965-8_1 D2 10.1007/978-3-642-38965-8 PG 10 WC Oncology; Infectious Diseases SC Oncology; Infectious Diseases GA BA0EB UT WOS:000331053500002 PM 24008290 ER PT S AU Zane, L Jeang, KT AF Zane, Linda Jeang, Kuan-Teh BE Chang, MH Jeang, KT TI HTLV-1 and Leukemogenesis: Virus-Cell Interactions in the Development of Adult T-Cell Leukemia SO VIRUSES AND HUMAN CANCER: FROM BASIC SCIENCE TO CLINICAL PREVENTION SE Recent Results in Cancer Research LA English DT Article; Book Chapter ID NF-KAPPA-B; TYPE-1 TAX PROTEIN; I-INFECTED CELLS; FAS-MEDIATED APOPTOSIS; TROPICAL SPASTIC PARAPARESIS; ONCOGENE PRODUCT TAX; LYMPHOTROPIC-VIRUS; TRANSGENIC MICE; DNA-DAMAGE; CYCLE PROGRESSION AB Human T-cell lymphotropic virus type 1 (HTLV-1) was originally discovered in the early 1980s. It is the first retrovirus to be unambiguously linked causally to a human cancer. HTLV-1 currently infects approximately 20 million people worldwide. In this chapter, we review progress made over the last 30 years in our understanding of HTLV-1 infection, replication, gene expression, and cellular transformation. C1 [Zane, Linda; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM KJEANG@nih.gov FU Intramural NIH HHS NR 155 TC 0 Z9 0 U1 0 U2 11 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 978-3-642-38965-8; 978-3-642-38964-1 J9 RECENT RESULTS CANC JI Rec. Res. Camcer Res. PY 2014 VL 193 BP 191 EP 210 DI 10.1007/978-3-642-38965-8_11 D2 10.1007/978-3-642-38965-8 PG 20 WC Oncology; Infectious Diseases SC Oncology; Infectious Diseases GA BA0EB UT WOS:000331053500012 PM 24008300 ER PT J AU Klabunde, CN Clauser, SB Liu, BM Pronk, NP Ballard-Barbash, R Huang, TTK Smith, AW AF Klabunde, Carrie N. Clauser, Steven B. Liu, Benmei Pronk, Nicolaas P. Ballard-Barbash, Rachel Huang, Terry T. -K. Smith, Ashley Wilder TI Organization of Primary Care Practice for Providing Energy Balance Care SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE Primary Care; Physicians; Physician's Practice Patterns; Primary Health Care-Organization and Administration; Energy Balance; Health Care Surveys; Prevention Research. Manuscript format: research; Research purpose; descriptive; modeling/relationship testing; Study design: nonexperimental; Outcome measure: behavioral; Setting: clinical/health care; Health focus: fitness/physical activity; nutrition; and weight control; Strategy: policy; Target population age: adults; Target population circumstances: education; geographic location; and race/ethnicity ID FORCE RECOMMENDATION STATEMENT; WEIGHT-RELATED CARE; PREVENTIVE SERVICES; PHYSICAL-ACTIVITY; FAMILY PHYSICIANS; NATIONAL-SURVEY; OBESITY; US; EXERCISE; PATIENT AB Purpose. Primary care physicians (PCPs) may not adequately counsel or monitor patients regarding diet, physical activity, and weight control (i. e., provide energy balance care). We assessed the organization of PCPs' practices for providing this care. Design. The study design was a nationally representative survey conducted in 2008. Setting. The study setting was U. S. primary care practices. Subjects. A total of 1740 PCPs completed two sequential questionnaires (response rate, 55.5%). Measures. The study measured PCPs' reports of practice resources, and the frequency of body mass index assessment, counseling, referral for further evaluation/management, and monitoring of patients for energy balance care. Analysis. Descriptive statistics and logistic regression modeling were used. Results. More than 80% of PCPs reported having information resources on diet, physical activity, or weight control available in waiting/exam rooms, but fewer billed (45%), used reminder systems (, 30%), or received incentive payments (3%) for energy balance care. A total of 26% reported regularly assessing body mass index and always/often providing counseling as well as tracking patients for progress related to energy balance. In multivariate analyses, PCPs in practices with full electronic health records or those that bill for energy balance care provided this care more often and more comprehensively. There were strong specialty differences, with pediatricians more likely (odds ratio, 1.78; 95% confidence interval, 1.262.51) and obstetrician/gynecologists less likely (odds ratio, 0.28; 95% confidence interval, 0.17-0.44) than others to provide energy balance care. nce care. Further research is needed to understand PCP care-related specialty differences. C1 [Klabunde, Carrie N.; Clauser, Steven B.; Ballard-Barbash, Rachel; Smith, Ashley Wilder] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Liu, Benmei] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Pronk, Nicolaas P.] HealthPartners, Bloomington, MN USA. [Huang, Terry T. -K.] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Hlth Promot & Social & Behav Hlth, Omaha, NE USA. RP Klabunde, CN (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 3E442, Bethesda, MD 20892 USA. EM KlabundC@mail.nih.gov FU NCI NIH HHS [N02-PC-61301] NR 52 TC 2 Z9 2 U1 0 U2 3 PU AMER JOURNAL HEALTH PROMOTION INC PI TROY PA PO BOX 1254, TROY, MI 48099-1254 USA SN 0890-1171 EI 2168-6602 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD JAN-FEB PY 2014 VL 28 IS 3 BP E67 EP E80 DI 10.4278/ajhp.121219-QUAN-626 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AB6JS UT WOS:000331894900002 PM 24200333 ER PT J AU Ioannidis, JPA Zhou, Y Chang, CQ Schully, SD Khoury, MJ Freedman, AN AF Ioannidis, J. P. A. Zhou, Y. Chang, C. Q. Schully, S. D. Khoury, M. J. Freedman, A. N. TI Potential increased risk of cancer from commonly used medications: an umbrella review of meta-analyses SO ANNALS OF ONCOLOGY LA English DT Review DE cancer; meta-analysis; pharmacoepidemiology; randomized trials; review ID RANDOMIZED CONTROLLED-TRIALS; CONVERTING-ENZYME-INHIBITORS; NECROSIS-FACTOR THERAPY; CLINICAL-TRIALS; RHEUMATOID-ARTHRITIS; CARDIOVASCULAR-DISEASE; COLORECTAL-CANCER; STATIN THERAPY; PANCREATIC-CANCER; LDL CHOLESTEROL AB Several commonly used medications have been associated with increased cancer risk in the literature. Here, we evaluated the strength and consistency of these claims in published meta-analyses. We carried out an umbrella review of 74 meta-analysis articles addressing the association of commonly used medications (antidiabetics, antihyperlipidemics, antihypertensives, antirheumatics, drugs for osteoporosis, and others) with cancer risk where at least one meta-analysis in the medication class included some data from randomized trials. Overall, 51 articles found no statistically significant differences, 13 found some decreased cancer risk, and 11 found some increased risk (one reported both increased and decreased risks). The 11 meta-analyses that found some increased risks reported 16 increased risk estimates, of which 5 pertained to overall cancer and 11 to site-specific cancer. Six of the 16 estimates were derived from randomized trials and 10 from observational data. Estimates of increased risk were strongly inversely correlated with the amount of evidence (number of cancer cases) (Spearman's correlation coefficient = -0.77, P < 0.001). In 4 of the 16 topics, another meta-analysis existed that was larger (n = 2) or included better controlled data (n = 2) and in all 4 cases there was no statistically significantly increased risk of malignancy. No medication or class had substantial and consistent evidence for increased risk of malignancy. However, for most medications we cannot exclude small risks or risks in population subsets. Such risks are unlikely to be possible to document robustly unless very large, collaborative studies with standardized analyses and no selective reporting are carried out. C1 [Ioannidis, J. P. A.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Dept Med, Stanford, CA 94305 USA. [Ioannidis, J. P. A.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Ioannidis, J. P. A.] Stanford Univ, Sch Humanities & Sci, Dept Stat, Stanford, CA 94305 USA. [Zhou, Y.] Georgetown Univ, Canc Control Program, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Chang, C. Q.; Schully, S. D.; Khoury, M. J.; Freedman, A. N.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Khoury, M. J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. RP Ioannidis, JPA (reprint author), Stanford Univ, Sch Med, Stanford Prevent Res Ctr, 1265 Welch Rd,MSOB X306, Stanford, CA 94305 USA. EM jioannid@stanford.edu NR 88 TC 10 Z9 10 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2014 VL 25 IS 1 BP 16 EP 23 DI 10.1093/annonc/mdt372 PG 8 WC Oncology SC Oncology GA AA7HR UT WOS:000331268800004 PM 24310915 ER PT J AU Duffy, AG Greten, TF AF Duffy, A. G. Greten, T. F. TI Immunological off-target effects of standard treatments in gastrointestinal cancers SO ANNALS OF ONCOLOGY LA English DT Review DE pancreatic; immune; myeloid-derived suppressor cells; colorectal; CTLA4 ID METASTATIC COLORECTAL-CANCER; ENDOTHELIAL GROWTH-FACTOR; DEPENDENT CELLULAR CYTOTOXICITY; REGULATORY T-CELLS; CETUXIMAB PLUS IRINOTECAN; POTENT IMMUNE-RESPONSES; DENDRITIC CELLS; SUPPRESSOR-CELLS; PANCREATIC-CANCER; PHASE-III AB The effects on immune cells and the inflammatory microenvironment of commonly applied cancer treatments (chemotherapeutic or biologic agents, interventional radiologic procedures) have become better appreciated. Likewise, the contribution of the immune system toward the effectiveness of these treatments is clearer. The relevance of immune evasion by developing tumors is endorsed by its inclusion as one of the (updated) hallmarks of cancer. A greater understanding of this dimension can potentially lead to novel applications of existing standard of care therapies, in addition to potentiating their effect. This review summarizes the immune aspects of currently employed therapies-cytotoxic chemotherapeutics, biologic agents and interventional radiologic procedures-in solid tumor malignancies with a particular focus on those agents used in gastrointestinal cancers. C1 [Duffy, A. G.; Greten, T. F.] NCI, GI Malignancy Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Greten, TF (reprint author), NCI, 9000 Rockville Pike,10-12N224, Bethesda, MD 20892 USA. EM tim.greten@nih.gov FU NIH FX Both authors are NIH employees and are therefore funded by the NIH. NR 83 TC 7 Z9 7 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2014 VL 25 IS 1 BP 24 EP 32 DI 10.1093/annonc/mdt349 PG 10 WC Oncology SC Oncology GA AA7HR UT WOS:000331268800005 PM 24201974 ER PT J AU Lee, JM Ledermann, JA Kohn, EC AF Lee, J-m. Ledermann, J. A. Kohn, E. C. TI PARP Inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies SO ANNALS OF ONCOLOGY LA English DT Review DE parp inhibitor; brca-like cancers; brca1/2 mutation; brca1/2 mutation-associated cancers ID EPITHELIAL OVARIAN-CANCER; POLY(ADP-RIBOSE) POLYMERASE INHIBITORS; PEGYLATED LIPOSOMAL DOXORUBICIN; REFRACTORY SOLID TUMORS; HOMOLOGOUS RECOMBINATION; BREAST-CANCER; PHASE-I; MAMMARY-TUMORS; DNA-DAMAGE; OPEN-LABEL AB Poly(ADP-ribose) polymerase inhibitors (PARPis) have shown promising activity in patients with BRCA1/2 mutation-associated (BRCA1/2(MUT+)) ovarian and breast cancers. Accumulating evidence suggests that PARPi may have a wider application in the treatment of sporadic high-grade serous ovarian cancer, and cancers defective in DNA repair pathways, such as prostate, endometrial, and pancreatic cancers. Several PARPis are currently in phase 1/2 clinical investigation, with registration trials now being designed. Olaparib, one of the most studied PARPis, has demonstrated activity in BRCA1/2(MUT+) and BRCA-like sporadic ovarian and breast cancers, and looks promising in prostate and pancreatic cancers. Understanding more about the molecular abnormalities involved in BRCA-like tumors, exploring novel therapeutic trial strategies and drug combinations, and defining potential predictive biomarkers, is critical to rapidly advancing the field of PARPi therapy and improve clinical outcomes. C1 [Lee, J-m.; Kohn, E. C.] NCI, Mol Signaling Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Ledermann, J. A.] UCL, UCL Canc Inst, London, England. RP Lee, JM (reprint author), Med Oncol Branch, 10 Ctr Dr MSC1906,Bldg10,Room12N-226, Bethesda, MD 20892 USA. EM leej6@mail.nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health, USA FX This work was supported by the Intramural Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, USA. No external funding was provided for this study. NR 73 TC 86 Z9 88 U1 5 U2 44 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2014 VL 25 IS 1 BP 32 EP 40 DI 10.1093/annonc/mdt384 PG 9 WC Oncology SC Oncology GA AA7HR UT WOS:000331268800006 PM 24225019 ER PT J AU Leoncini, E Ricciardi, W Cadoni, G Arzani, D Petrelli, L Paludetti, G Brennan, P Luce, D Stucker, I Matsuo, K Talamini, R La Vecchia, C Olshan, AF Winn, DM Herrero, R Franceschi, S Castellsague, X Muscat, J Morgenstern, H Zhang, ZF Levi, F Dal Maso, L Kelsey, K McClean, M Vaughan, T Lazarus, P Purdue, MP Hayes, RB Chen, C Schwartz, SM Shangina, O Koifman, S Ahrens, W Matos, E Lagiou, P Lissowska, J Szeszenia-Dabrowska, N Fernandez, L Menezes, A Agudo, A Daudt, AW Richiardi, L Kjaerheim, K Mates, D Betka, J Yu, GP Schantz, S Simonato, L Brenner, H Conway, DI Macfarlane, TV Thomson, P Fabianova, E Znaor, A Rudnai, P Healy, C Boffetta, P Chuang, SC Lee, YCA Hashibe, M Boccia, S AF Leoncini, Emanuele Ricciardi, Walter Cadoni, Gabriella Arzani, Dario Petrelli, Livia Paludetti, Gaetano Brennan, Paul Luce, Daniele Stucker, Isabelle Matsuo, Keitaro Talamini, Renato La Vecchia, Carlo Olshan, Andrew F. Winn, Deborah M. Herrero, Rolando Franceschi, Silvia Castellsague, Xavier Muscat, Joshua Morgenstern, Hal Zhang, Zuo-Feng Levi, Fabio Dal Maso, Luigino Kelsey, Karl McClean, Michael Vaughan, Thomas L. Lazarus, Philip Purdue, Mark P. Hayes, Richard B. Chen, Chu Schwartz, Stephen M. Shangina, Oxana Koifman, Sergio Ahrens, Wolfgang Matos, Elena Lagiou, Pagona Lissowska, Jolanta Szeszenia-Dabrowska, Neonila Fernandez, Leticia Menezes, Ana Agudo, Antonio Daudt, Alexander W. Richiardi, Lorenzo Kjaerheim, Kristina Mates, Dana Betka, Jaroslav Yu, Guo-Pei Schantz, Stimson Simonato, Lorenzo Brenner, Hermann Conway, David I. Macfarlane, Tatiana V. Thomson, Peter Fabianova, Eleonora Znaor, Ariana Rudnai, Peter Healy, Claire Boffetta, Paolo Chuang, Shu-Chun Lee, Yuan-Chin Amy Hashibe, Mia Boccia, Stefania TI Adult height and head and neck cancer: a pooled analysis within the INHANCE Consortium SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Cancer; Height; Consortium; Head and neck neoplasms ID BODY-MASS INDEX; INTERNATIONAL HEAD; EPIDEMIOLOGY CONSORTIUM; CARDIORESPIRATORY DISEASE; SECULAR TRENDS; RISK-FACTORS; LEG LENGTH; METAANALYSIS; COHORT; WOMEN AB Several epidemiological studies have shown a positive association between adult height and cancer incidence. The only study conducted among women on mouth and pharynx cancer risk, however, reported an inverse association. This study aims to investigate the association between height and the risk of head and neck cancer (HNC) within a large international consortium of HNC. We analyzed pooled individual-level data from 24 case-control studies participating in the International Head and Neck Cancer Epidemiology Consortium. Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated separately for men and women for associations between height and HNC risk. Educational level, tobacco smoking, and alcohol consumption were included in all regression models. Stratified analyses by HNC subsites were performed. This project included 17,666 cases and 28,198 controls. We found an inverse association between height and HNC (adjusted OR per 10 cm height = 0.91, 95 % CI 0.86-0.95 for men; adjusted OR = 0.86, 95 % CI 0.79-0.93 for women). In men, the estimated OR did vary by educational level, smoking status, geographic area, and control source. No differences by subsites were detected. Adult height is inversely associated with HNC risk. As height can be considered a marker of childhood illness and low energy intake, the inverse association is consistent with prior studies showing that HNC occur more frequently among deprived individuals. Further studies designed to elucidate the mechanism of such association would be warranted. C1 [Leoncini, Emanuele; Ricciardi, Walter; Arzani, Dario; Boccia, Stefania] Univ Cattolica Sacro Cuore, Sect Hyg, Inst Publ Hlth, Rome, Italy. [Cadoni, Gabriella; Petrelli, Livia; Paludetti, Gaetano] Univ Cattolica Sacro Cuore, Inst Otorhinolaryngol, Rome, Italy. [Brennan, Paul; Herrero, Rolando; Franceschi, Silvia] Int Agcy Res Canc, F-69372 Lyon, France. [Luce, Daniele; Stucker, Isabelle] Ctr Res Epidemiol & Populat Hlth, INSERM, UMRS 1018, Villejuif, France. [Matsuo, Keitaro] Aichi Canc Ctr Res Inst, Nagoya, Aichi, Japan. [Talamini, Renato; Dal Maso, Luigino] Ctr Riferimento Oncol IRCCS, Aviano, Italy. [La Vecchia, Carlo] IRCCS Ist Ric Farmacol Mario Negri, Milan, Italy. [La Vecchia, Carlo] Univ Milan, Milan, Italy. [Olshan, Andrew F.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Winn, Deborah M.; Purdue, Mark P.] NCI, NIH, Bethesda, MD 20892 USA. [Castellsague, Xavier] CIBER ESP, IDIBELL, ICO, Barcelona, Spain. [Muscat, Joshua; Lazarus, Philip] Penn State Coll Med, Hershey, PA USA. [Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Zhang, Zuo-Feng] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Zhang, Zuo-Feng] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. [Levi, Fabio] Univ Lausanne Hosp, Canc Epidemiol Unit, Inst Social & Prevent Med IUMSP, Lausanne, Switzerland. [Kelsey, Karl] Brown Univ, Providence, RI 02912 USA. [McClean, Michael] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Vaughan, Thomas L.; Chen, Chu; Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, New York, NY USA. [Shangina, Oxana] Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia. [Koifman, Sergio] Fundacao Oswaldo Cruz, Escola Nacl Saude Publ, Rio De Janeiro, Brazil. [Ahrens, Wolfgang] Leibniz Inst Prevent Res & Epidemiol BIPS, Bremen, Germany. [Ahrens, Wolfgang] Univ Bremen, Dept Math & Comp Sci, D-28359 Bremen, Germany. [Matos, Elena] Univ Buenos Aires, Inst Oncol Angel H Roffo, Buenos Aires, DF, Argentina. [Lagiou, Pagona] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Szeszenia-Dabrowska, Neonila] Inst Occupat Med, Lodz, Poland. [Fernandez, Leticia] Inst Oncol & Radiobiol, Havana, Cuba. [Menezes, Ana] Univ Fed Pelotas, Pelotas, Brazil. [Agudo, Antonio] IDIBELL, Catalan Inst Oncol ICO, Barcelona, Spain. [Daudt, Alexander W.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Richiardi, Lorenzo] Univ Turin, Dept Med Sci, Turin, Italy. [Kjaerheim, Kristina] Canc Registry Norway, Oslo, Norway. [Mates, Dana] Natl Inst Publ Hlth, Bucharest, Romania. [Betka, Jaroslav] Charles Univ Prague, Dept Otorhinolaryngol Head & Neck Surg, Fac Med 1, Prague, Czech Republic. [Betka, Jaroslav] Univ Hosp Motol, Prague, Czech Republic. [Yu, Guo-Pei; Schantz, Stimson] New York Eye & Ear Infirm, New York, NY 10003 USA. [Simonato, Lorenzo] Univ Padua, Padua, Italy. [Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Conway, David I.] Univ Glasgow, Sch Dent, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland. [Macfarlane, Tatiana V.] Univ Aberdeen, Sch Dent, Aberdeen, Scotland. [Thomson, Peter] Newcastle Univ, Sch Dent Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia. [Znaor, Ariana] Croatian Natl Canc Registry, Zagreb, Croatia. [Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary. [Healy, Claire] Univ Dublin Trinity Coll, Sch Dent Sci, Dublin 2, Ireland. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. [Chuang, Shu-Chun] Univ London Imperial Coll Sci Technol & Med, London, England. [Lee, Yuan-Chin Amy; Hashibe, Mia] Univ Utah, Sch Med, Dept Family & Prevent Med, Salt Lake City, UT 84112 USA. [Boccia, Stefania] IRCCS San Raffaele Pisana, Rome, Italy. RP Boccia, S (reprint author), Univ Cattolica Sacro Cuore, Sect Hyg, Inst Publ Hlth, Rome, Italy. EM sboccia@rm.unicatt.it RI , emanuele/A-5466-2010; Thomson, Peter/L-7719-2016; Chuang, Shu-Chun/N-3358-2013; McClean, Michael/J-2934-2015; Castellsague Pique, Xavier/N-5795-2014; LUCE, Daniele/J-9125-2015; Szeszenia-Dabrowska, Neonila/F-7190-2010; Purdue, Mark/C-9228-2016; Agudo, Antonio/J-1805-2016; Brenner, Hermann/B-4627-2017; Menezes, Ana/G-7266-2012; OI Luce, Daniele/0000-0002-1708-4584; Matsuo, Keitaro/0000-0003-1761-6314; Ahrens, Wolfgang/0000-0003-3777-570X; , emanuele/0000-0002-7669-8535; dal maso, luigino/0000-0001-6163-200X; Thomson, Peter/0000-0002-2007-7975; Macfarlane, Tatiana/0000-0002-9392-0812; richiardi, lorenzo/0000-0003-0316-9402; La Vecchia, Carlo/0000-0003-1441-897X; Kjaerheim, Kristina/0000-0003-0691-3735; Hayes, Richard/0000-0002-0918-661X; Schwartz, Stephen/0000-0001-7499-8502; Healy, Claire M/0000-0001-7940-4611; mates, dana/0000-0002-6219-9807; Castellsague Pique, Xavier/0000-0002-0802-3595; Purdue, Mark/0000-0003-1177-3108; Brenner, Hermann/0000-0002-6129-1572; Agudo, Antonio/0000-0001-9900-5677 FU World Cancer Research Fund; European Commission INCO-COPERNICUS Program [IC15- CT98-0332]; French National Research Agency (ANR); French National Cancer Institute (INCA); French Agency for Food, Environmental and Occupational Health and Safety (ANSES); French Association for Research on Cancer (ARC); Fondation pour la Recherche Medicale (FRM); French Institute for Public Health Surveillance (InVS); Fondation de France; Ministry of Labour; Ministry of Health; Ministry of Science, Research and Arts Baden-Wurttemberg; Italian Association for Research on Cancer (AIRC); Italian League Against Cancer; Italian Ministry of Research; Italian Association for Research on Cancer (AIRC) [10068]; Italian Ministry of Education [PRIN 2009 X8YCBN]; AIRC (Italian Agency for Research on Cancer) [10491]; Swiss League against Cancer; Swiss Research against Cancer/Oncosuisse [KFS-700, OCS-1633]; European Community [QLK1-CT-2001-00182]; National Institutes of Health (NIH) US [R01CA078609, R01CA100679]; National Institute of Health (NIH) US [P50CA090388, R01DA011386, R03CA077954, T32CA009142, U01CA096134, R21ES011667, P01CA068384 K07CA104231, R01CA061188, R01CA048996, R01DE012609, P01CA068384, K07CA104231, R01DE013158]; Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center; NIH [R01CA051845, R01CA030022]; National Institute of Environmental Health Sciences [P30ES010126]; NCI, NIH, United States; National Institutes of Health (NCI) US; NIDCR; Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina; IMIM (Barcelona); Fundaco de Amparo a Pesquisa no Estado de Sao Paulo (FAPESP) [01/01768-2]; European Commission [IC18-CT97-0222]; Ministry of Education, Science, Sports, Culture and Technology of Japan [17015052]; Ministry of Health, Labor and Welfare of Japan [H20-002]; Fondo de Investigaciones Sanitarias (FIS) of the Spanish Government [FIS 97/0024, FIS 97/0662, BAE 01/5013]; International Union Against Cancer (UICC); Yamagiwa-Yoshida Memorial International Cancer Study Grant; Fondazione Veronesi FX The authors would like to thank all of the participants who took part in this research for providing us very insightful and constructive comments, which helped improve this manuscript. The individual studies were supported by the following grants: Central Europe study: World Cancer Research Fund and the European Commission INCO-COPERNICUS Program (IC15- CT98-0332). France study (2001-2007): French National Research Agency (ANR); French National Cancer Institute (INCA); French Agency for Food, Environmental and Occupational Health and Safety (ANSES); French Association for Research on Cancer (ARC); Fondation pour la Recherche Medicale (FRM); French Institute for Public Health Surveillance (InVS); Fondation de France; Ministry of Labour; Ministry of Health. Saarland study: Ministry of Science, Research and Arts Baden-Wurttemberg. Aviano study: Italian Association for Research on Cancer (AIRC), Italian League Against Cancer and Italian Ministry of Research. Milan study (1984-1989): Italian Association for Research on Cancer (AIRC). Milan study (2006-2009): Italian Association for Research on Cancer (AIRC, grant n. 10068) and Italian Ministry of Education (PRIN 2009 X8YCBN). Italy Multicenter study: Italian Association for Research on Cancer (AIRC), Italian League Against Cancer and Italian Ministry of Research. Rome study (2010-2013): AIRC (Italian Agency for Research on Cancer), n. 10491. Swiss study: Swiss League against Cancer and the Swiss Research against Cancer/Oncosuisse (KFS-700, OCS-1633). Western Europe study: European Community (5th Framework Programme) (QLK1-CT-2001-00182). Boston study: National Institutes of Health (NIH) US (R01CA078609, R01CA100679). Los Angeles study: National Institute of Health (NIH) US (P50CA090388, R01DA011386, R03CA077954, T32CA009142, U01CA096134, R21ES011667) and the Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center. MSKCC study: NIH (R01CA051845). New York Multicenter study: National Institutes of Health (NIH) US (P01CA068384 K07CA104231). North Carolina (1994-1997): National Institutes of Health (NIH) US (R01CA061188), and in part by a grant from the National Institute of Environmental Health Sciences (P30ES010126). Seattle-LEO study: NIH (R01CA030022). Seattle study: National Institutes of Health (NIH) US (R01CA048996, R01DE012609). Tampa study: National Institutes of Health (NIH) US (P01CA068384, K07CA104231, R01DE013158). US Multicenter study: The Intramural Program of the NCI, NIH, United States. Puerto Rico study: jointly funded by National Institutes of Health (NCI) US and NIDCR intramural programs. Latin America study: Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina, IMIM (Barcelona), Fundaco de Amparo a Pesquisa no Estado de Sao Paulo (FAPESP) (No 01/01768-2), and European Commission (IC18-CT97-0222). Japan (1988-2000 and 2001-2005): Scientific Research grant from the Ministry of Education, Science, Sports, Culture and Technology of Japan (17015052) and grant for the Third-Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan (H20-002). IARC Multicenter study: Fondo de Investigaciones Sanitarias (FIS) of the Spanish Government (FIS 97/0024, FIS 97/0662, BAE 01/5013), International Union Against Cancer (UICC), and Yamagiwa-Yoshida Memorial International Cancer Study Grant. The work of EL was supported by Fondazione Veronesi. NR 53 TC 8 Z9 8 U1 3 U2 23 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 EI 1573-7284 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD JAN PY 2014 VL 29 IS 1 BP 35 EP 48 DI 10.1007/s10654-013-9863-2 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AB2TO UT WOS:000331645200004 PM 24271556 ER PT J AU Meyers, KJ Mares, JA Igo, RP Truitt, B Liu, Z Millen, AE Klein, M Johnson, EJ Engelman, CD Karki, CK Blodi, B Gehrs, K Tinker, L Wallace, R Robinson, J LeBlanc, ES Sarto, G Bernstein, PS SanGiovanni, JP Iyengar, SK AF Meyers, Kristin J. Mares, Julie A. Igo, Robert P., Jr. Truitt, Barbara Liu, Zhe Millen, Amy E. Klein, Michael Johnson, Elizabeth J. Engelman, Corinne D. Karki, Chitra K. Blodi, Barbara Gehrs, Karen Tinker, Lesley Wallace, Robert Robinson, Jennifer LeBlanc, Erin S. Sarto, Gloria Bernstein, Paul S. SanGiovanni, John Paul Iyengar, Sudha K. TI Genetic Evidence for Role of Carotenoids in Age-Related Macular Degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE macular degeneration; carotenoids; genes ID GENOME-WIDE ASSOCIATION; SINGLE NUCLEOTIDE POLYMORPHISMS; POLYUNSATURATED FATTY-ACIDS; PIGMENT OPTICAL-DENSITY; RECEPTOR CLASS-B; BETA-CAROTENE; LUTEIN SUPPLEMENTATION; HUMAN RETINA; VITAMIN-A; SR-BI AB PURPOSE. We tested variants in genes related to lutein and zeaxanthin status for association with age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study (CAREDS). METHODS. Of 2005 CAREDS participants, 1663 were graded for AMD from fundus photography and genotyped for 424 single nucleotide polymorphisms (SNPs) from 24 candidate genes for carotenoid status. Of 337 AMD cases 91% had early or intermediate AMD. The SNPs were tested individually for association with AMD using logistic regression. A carotenoid-related genetic risk model was built using backward selection and compared to existing AMD risk factors using the area under the receiver operating characteristic curve (AUC). RESULTS. A total of 24 variants from five genes (BCMO1, BCO2, NPCL1L1, ABCG8, and FADS2) not previously related to AMD and four genes related to AMD in previous studies (SCARB1, ABCA1, APOE, and ALDH3A2) were associated independently with AMD, after adjusting for age and ancestry. Variants in all genes (not always the identical SNPs) were associated with lutein and zeaxanthin in serum and/or macula, in this or other samples, except for BCO2 and FADS2. A genetic risk score including nine variants significantly (P = 0.002) discriminated between AMD cases and controls beyond age, smoking, CFH Y402H, and ARMS2 A69S. The odds ratio (95% confidence interval) for AMD among women in the highest versus lowest quintile for the risk score was 3.1 (2.0-4.9). CONCLUSIONS. Variants in genes related to lutein and zeaxanthin status were associated with AMD in CAREDS, adding to the body of evidence supporting a protective role of lutein and zeaxanthin in risk of AMD. C1 [Meyers, Kristin J.; Mares, Julie A.; Liu, Zhe; Karki, Chitra K.; Blodi, Barbara] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, McPherson Eye Res Inst, Madison, WI 53726 USA. [Igo, Robert P., Jr.; Truitt, Barbara; Iyengar, Sudha K.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Millen, Amy E.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Klein, Michael] Oregon Hlth & Sci Univ, Dept Ophthalmol, Casey Eye Inst, Portland, OR 97201 USA. [Johnson, Elizabeth J.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Engelman, Corinne D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53726 USA. [Gehrs, Karen] Univ Iowa, Carver Coll Med, Dept Ophthalmol & Visual Sci, Iowa City, IA USA. [Tinker, Lesley] Fred Hutchinson Canc Res Ctr, Dept Canc Prevent Res Program, Seattle, WA 98104 USA. [Wallace, Robert; Robinson, Jennifer] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Robinson, Jennifer] Univ Iowa, Dept Med, Coll Publ Hlth, Iowa City, IA 52242 USA. [LeBlanc, Erin S.] Kaiser Ctr Hlth Res, Portland, OR USA. [Sarto, Gloria] Univ Wisconsin, Sch Med & Publ Hlth, Dept Obstet & Gynecol, Madison, WI 53726 USA. [Bernstein, Paul S.] Univ Utah Hlth Care, Moran Eye Ctr, Salt Lake City, UT USA. [SanGiovanni, John Paul] NEI, NIH, Clin Trials Branch, Bethesda, MD 20892 USA. RP Mares, JA (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, 610 N Walnut St,1063 WARF, Madison, WI 53726 USA. EM jmarespe@wisc.edu FU National Institutes of Health, National Eye Institute [EY013018, EY016886]; Retina Research Foundation and Research; National Heart, Lung, and Blood Institute [N01 WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; Women's Health Initiative FX Supported by the National Institutes of Health, National Eye Institute (Grants EY013018, EY016886), the Retina Research Foundation and Research to Prevent Blindness (CAREDS Study), and by the National Heart, Lung, and Blood Institute (Contracts N01 WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221; The Women's Health Initiative, to which CAREDS is ancillary). NR 119 TC 22 Z9 23 U1 3 U2 22 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2014 VL 55 IS 1 BP 587 EP 599 DI 10.1167/iovs.13-13216 PG 13 WC Ophthalmology SC Ophthalmology GA AB6DG UT WOS:000331877200069 PM 24346170 ER PT J AU Gericke, A Steege, A Manicam, C Bohmer, T Wess, J Pfeiffer, N AF Gericke, Adrian Steege, Andreas Manicam, Caroline Boehmer, Tobias Wess, Juergen Pfeiffer, Norbert TI Role of the M-3 Muscarinic Acetylcholine Receptor Subtype in Murine Ophthalmic Arteries After Endothelial Removal SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE acetylcholine; muscarinic receptors; vasoconstriction; ophthalmic arteries; mice ID OCULAR BLOOD-FLOW; SPONTANEOUSLY HYPERTENSIVE-RAT; CORONARY-ARTERY; DIABETES-MELLITUS; NITRIC-OXIDE; SACCHAROMYCES-CEREVISIAE; CHOLINERGIC DILATION; DEPENDENT RELAXATION; KNOCKOUT MICE; RABBIT AORTA AB PURPOSE. We tested the hypothesis that the M-3 muscarinic acetylcholine receptor subtype mediates cholinergic responses in murine ophthalmic arteries after endothelial removal. METHODS. Muscarinic receptor gene expression was determined in ophthalmic arteries with intact and with removed endothelium using real-time PCR. To examine the role of the M-3 receptor in mediating vascular responses, ophthalmic arteries from M-3 receptor-deficient mice (M3R(-/-)) and respective wild-type controls were studied in vitro. Functional studies were performed in nonpreconstricted arteries with either intact or removed endothelium using video microscopy. RESULTS. In endothelium-intact ophthalmic arteries, mRNA for all five muscarinic receptor subtypes was detected, but M-3 receptor mRNA was most abundant. In endothelium-removed ophthalmic arteries, M-1, M-2, and M-3 receptors displayed similar mRNA expression levels, which were higher than those for M-4 and M-5 receptors. In functional studies, acetylcholine evoked vasoconstriction in endothelium-removed arteries from wild-type mice that was virtually abolished after incubation with the muscarinic receptor blocker atropine, indicative of the involvement of muscarinic receptors. In concentration-response experiments, acetylcholine and carbachol concentration-dependently constricted endothelium-removed ophthalmic arteries from wild-type mice, but produced only negligible responses in arteries from M3R(-/-) mice. In contrast, acetylcholine concentration-dependently dilated ophthalmic arteries with intact endothelium from wild-type mice, but not from M3R(-/-) mice. Responses to the nitric oxide donor nitroprusside and to KCl did not differ between ophthalmic arteries from wild-type and M3R(-/-) mice, neither in endothelium-intact nor in endothelium-removed arteries. CONCLUSIONS. These findings provide evidence that in murine ophthalmic arteries the muscarinic M-3 receptor subtype mediates cholinergic endothelium-dependent vasodilation and endothelium-independent vasoconstriction. C1 [Gericke, Adrian; Manicam, Caroline; Boehmer, Tobias; Pfeiffer, Norbert] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Ophthalmol, D-55131 Mainz, Germany. [Steege, Andreas] Univ Med Ctr Regensburg, Dept Internal Med 2, Regensburg, Germany. [Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Gericke, A (reprint author), Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Ophthalmol, Langenbeckstr 1, D-55131 Mainz, Germany. EM adrian.gericke@gmx.net FU National Institutes of Health (NIH); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, Maryland FX Supported by funds from the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, Maryland. The authors alone are responsible for the content and writing of the paper. NR 48 TC 5 Z9 5 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2014 VL 55 IS 1 BP 625 EP 631 DI 10.1167/iovs.13-13549 PG 7 WC Ophthalmology SC Ophthalmology GA AB6DG UT WOS:000331877200072 PM 24408978 ER PT J AU Giovannetti, E Wang, QY Avan, A Funel, N Lagerweij, T Lee, JH Caretti, V van der Velde, A Boggi, U Wang, YS Vasile, E Peters, GJ Wurdinger, T Giaccone, G AF Giovannetti, Elisa Wang, Qiuyan Avan, Amir Funel, Niccola Lagerweij, Tonny Lee, Jih-Hsiang Caretti, Viola van der Velde, Arjan Boggi, Ugo Wang, Yisong Vasile, Enrico Peters, Godefridus J. Wurdinger, Thomas Giaccone, Giuseppe TI Role of CYB5A in Pancreatic Cancer Prognosis and Autophagy Modulation SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DUCTAL ADENOCARCINOMA; SIGNALING PATHWAYS; LUNG-CANCER; CELL-DEATH; GENE; EXPRESSION; TRAF6; CHEMOTHERAPY; GEMCITABINE; GROWTH AB Background Loss of 18q22.3 is a prognostic marker in pancreatic ductal adenocarcinoma (PDAC). This study investigated genes encoded by this cytoband. Methods We studied mRNA/protein expression in radically resected (n = 130) and metastatic patients (n = 50). The role of CYB5A was tested in 11 PDAC cell lines and five primary cultures through retrovirus-mediated upregulation and small interfering RNA using wound-healing, invasion, annexin-V, electron microscopy, and autophagic assays, as well as autophagy genes and kinases arrays. CYB5A+ orthotopic models (n = 6 mice/group) were monitored by Firefly and Gaussia-luciferase bioluminescence, magnetic resonance imaging, and high-frequency ultrasound. Data were analyzed by t test, Fisher exact-test, log-rank test and Cox proportional hazards models. All statistical tests were two-sided. Results Both resected and metastatic patients with low mRNA or protein expression of CYB5A had statistically significantly shorter survival (eg, median = 16.7 months, 95% confidence interval [CI] = 13.5 to 19.9; vs median = 24.8 months, 95% CI = 12.8 to 36.9; P = .02, two-sided log-rank test; n = 82 radically resected PDACs), and multivariable analyses confirmed prognostic relevance. Moreover, we characterized a novel function to CYB5A, autophagy induction, concomitant with reduced proliferation and migration/invasion of PDAC cells. Network analysis of proautophagic pathways suggested CYB5A interaction with TRAF6, which was confirmed by TRAF6 downregulation after CYB5A reconstitution (-69% in SU.86.86-CYB5A+; P = .005, two-sided t test). CYB5A silencing had opposite effects, restoring TRAF6 expression and wound healing. In vivo studies showed that CYB5A induced autophagy while inhibiting tumor growth/metastasis and increasing survival (median = 57 days, 95% CI = 52 to 61; vs median = 44 days, 95% CI = 21 to 57; P = .03, two-sided log-rank test). Conclusions These results define CYB5A as a novel prognostic factor for PDAC that exerts its tumor-suppressor function through autophagy induction and TRAF6 modulation. C1 [Giovannetti, Elisa; Avan, Amir; Peters, Godefridus J.] Vrije Univ Amsterdam, Dept Med Oncol, Med Ctr, NL-1081 HV Amsterdam, Netherlands. [Lagerweij, Tonny; Caretti, Viola; Wurdinger, Thomas] Vrije Univ Amsterdam, Dept Neurosurg, Med Ctr, NL-1081 HV Amsterdam, Netherlands. [van der Velde, Arjan] Vrije Univ Amsterdam, Ctr Integrat Bioinformat, NL-1081 HV Amsterdam, Netherlands. [Funel, Niccola; Boggi, Ugo; Vasile, Enrico] Univ Pisa, Dept Ric Traslaz & Nuove Tecnol Med & Chirurg, Pisa, Italy. [Caretti, Viola] Stanford Univ, Dept Neurol, Stanford, CA 94305 USA. [Wurdinger, Thomas] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Wurdinger, Thomas] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Wang, Qiuyan; Lee, Jih-Hsiang; Wang, Yisong; Giaccone, Giuseppe] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Giovannetti, E (reprint author), Vrije Univ Amsterdam, Dept Med Oncol, Canc Ctr Amsterdam, Med Ctr, CCA Rm 1-52,De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM e.giovannetti@vumc.nl RI Giaccone, Giuseppe/E-8297-2017; OI Giaccone, Giuseppe/0000-0002-5023-7562; Lagerweij, Tonny/0000-0003-1043-7452; Giovannetti, Elisa/0000-0002-7565-7504; van der Velde, Arjan/0000-0003-1086-0859; Funel, Niccola/0000-0002-5028-2363 FU Netherlands Organization for Scientific Research; Marie Curie International Fellowship; CCA Foundation; Italian Minister of Research; Istituto Toscano Tumori; National Institutes of Health/National Cancer Institute intramural research funds; U.S. National Institute of General Medical Sciences [GM070743]; National Resource for Network Biology [P41 RR031228, GM103504]; Veni grant FX This work was partially supported by grants from Netherlands Organization for Scientific Research; Veni grant (to EG); Marie Curie International Fellowship (to EG); CCA Foundation 2012 (to EG, AA, GJP); Italian Minister of Research; PRIN-2009 (to UB, NF, EG); Istituto Toscano Tumori (to UB, NF, EV, EG), and National Institutes of Health/National Cancer Institute intramural research funds. Funding for continued development and maintenance of Cytoscape is provided by the U.S. National Institute of General Medical Sciences (GM070743). Cytoscape user support, education and new initiatives are supported by the National Resource for Network Biology (P41 RR031228 and GM103504). Further information is available at http://www.cytoscape.org/. NR 50 TC 9 Z9 9 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JAN PY 2014 VL 106 IS 1 AR djt346 DI 10.1093/jnci/djt346 PG 12 WC Oncology SC Oncology GA AB6IV UT WOS:000331891900006 PM 24301457 ER PT J AU Binukumar, BK Zheng, YL Shukla, V Amin, ND Grant, P Pant, HC AF Binukumar, B. K. Zheng, Ya-Li Shukla, Varsha Amin, Niranjana D. Grant, Philip Pant, Harish C. TI TFP5, a Peptide Derived from p35, a Cdk5 Neuronal Activator, Rescues Cortical Neurons from Glucose Toxicity SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; cyclin dependent kinase 5; diabetes; neuroinflammation; oxidative stress ID PANCREATIC BETA-CELLS; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; TAU HYPERPHOSPHORYLATION; DIABETIC COMPLICATIONS; INFLAMMATORY CYTOKINES; COGNITIVE PERFORMANCE; INDUCED EXPRESSION; INCREASED RISK; NEURODEGENERATION AB Multiple lines of evidence link the incidence of diabetes to the development of Alzheimer's disease (AD). Patients with diabetes have a 50 to 75% increased risk of developing AD. Cyclin dependent kinase 5 (Cdk5) is a serine/threonine protein kinase, which forms active complexes with p35 or p39, found principally in neurons and in pancreatic beta cells. Recent studies suggest that Cdk5 hyperactivity is a possible link between neuropathology seen in AD and diabetes. Previously, we identified P5, a truncated 24-aa peptide derived from the Cdk5 activator p35, later modified as TFP5, so as to penetrate the blood-brain barrier after intraperitoneal injections in AD model mice. This treatment inhibited abnormal Cdk5 hyperactivity and significantly rescued AD pathology in these mice. The present study explores the potential of TFP5 peptide to rescue high glucose (HG)-mediated toxicity in rat embryonic cortical neurons. HG exposure leads to Cdk5-p25 hyperactivity and oxidative stress marked by increased reactive oxygen species production, and decreased glutathione levels and superoxide dismutase activity. It also induces hyperphosphorylation of tau, neuroinflammation as evident from the increased expression of inflammatory cytokines like TNF-alpha, IL-1 beta, and IL-6, and apoptosis. Pretreatment of cortical neurons with TFP5 before HG exposure inhibited Cdk5-p25 hyperactivity and significantly attenuated oxidative stress by decreasing reactive oxygen species levels, while increasing superoxide dismutase activity and glutathione. Tau hyperphosphorylation, inflammation, and apoptosis induced by HG were also considerably reduced by pretreatment with TFP5. These results suggest that TFP5 peptide may be a novel candidate for type 2 diabetes therapy. C1 [Binukumar, B. K.; Zheng, Ya-Li; Shukla, Varsha; Amin, Niranjana D.; Grant, Philip; Pant, Harish C.] NINDS, Lab Neuronal Cytoskeletal Prot Regulat Sect, NIH, Bethesda, MD 20892 USA. [Zheng, Ya-Li] Ningxia Peoples Hosp, Dept Nephrol, Yinchuan, Ningxia Provinc, Peoples R China. RP Pant, HC (reprint author), NINDS, Lab Neuronal Cytoskeletal Prot Regulat Sect, NIH, Bethesda, MD 20892 USA. EM PantH@ninds.nih.gov FU NIH, National Institute of Neurological Disorders and Stroke FX This research was supported by the Intramural Research Programs of the NIH, National Institute of Neurological Disorders and Stroke. NR 37 TC 11 Z9 12 U1 1 U2 9 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 39 IS 4 BP 899 EP 909 DI 10.3233/JAD-131784 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AB5QD UT WOS:000331842500020 PM 24326517 ER PT J AU Rianon, NJ Lang, TF Siggeirsdottir, K Sigurdsson, G Eiriksdottir, G Sigurdsson, S Jonsson, BY Garcia, M Yu, BB Kapadia, AS Taylor, WC Selwyn, BJ Gudnason, V Launer, LJ Harris, TB AF Rianon, Nahid J. Lang, Thomas F. Siggeirsdottir, Kristin Sigurdsson, Gunnar Eiriksdottir, Gudny Sigurdsson, Sigurdur Jonsson, Brynjolfur Y. Garcia, Melissa Yu, Binbing Kapadia, Asha S. Taylor, Wendell C. Selwyn, Beatrice J. Gudnason, Vilmundur Launer, Lenore J. Harris, Tamara B. TI Fracture Risk Assessment in Older Adults Using a Combination of Selected Quantitative Computed Tomography Bone Measures: A Subanalysis of the Age, Gene/Environment Susceptibility-Reykjavik Study SO JOURNAL OF CLINICAL DENSITOMETRY LA English DT Article DE Bone mineral density; bone strength; elderly; fracture; quantitative computerized tomography ID HIP FRACTURE; PROXIMAL FEMUR; STRENGTH INDEXES; DENSITY; WOMEN; MEN; GEOMETRY; OSTEOPOROSIS; ASSOCIATION; STRATEGIES AB Bone mineral density (BMD) and geometric bone measures are individually associated with prevalent osteoporotic fractures. Whether an aggregate of these measures would better associate with fractures has not been examined. We examined relationships between self-reported fractures and selected bone measures acquired by quantitative computerized tomography (QCT), a composite bone score, and QCT-acquired dual-energy X-ray absorptiometry-like total femur BMD in 2110 men and 2682 women in the Age, Gene/Environment Susceptibility-Reykjavik Study. The combined bone score was generated by summing gender-specific Z-scores for 4 QCT measures: vertebral trabecular BMD, femur neck cortical thickness, femur neck trabecular BMD, and femur neck minimal cross-sectional area. Except for the latter measure, lower scores for QCT measures, singly and combined, showed positive (p < 0.05) associations with fractures. Results remained the same in stratified models for participants not taking bone-promoting medication. In women on bone-promoting medication, greater femur neck cortical thickness and trabecular BMD were significantly associated with fracture status. However, the association between fracture and combined bone score was not stronger than the associations between fracture and individual measures or total femur BMD. Thus, the selected measures did not all similarly associate with fracture status and did not appear to have an additive effect on fracture status. C1 [Rianon, Nahid J.] UT Med Sch Houston, Dept Internal Med, Div Geriatr & Palliat Med, Houston, TX 77030 USA. [Lang, Thomas F.] UCSF Sch Med, San Francisco, CA USA. [Siggeirsdottir, Kristin; Eiriksdottir, Gudny; Sigurdsson, Sigurdur; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Sigurdsson, Gunnar] Landspitali Univ Hosp, Dept Internal Med, Div Endocrinol & Metab, Reykjavik, Iceland. [Jonsson, Brynjolfur Y.] Univ Hosp, Malmo, Sweden. [Garcia, Melissa; Yu, Binbing; Harris, Tamara B.] NIA, LEDB, Bethesda, MD 20892 USA. [Kapadia, Asha S.; Taylor, Wendell C.; Selwyn, Beatrice J.] UTHSC Sch Publ Hlth, Houston, TX USA. [Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Launer, Lenore J.] NIA, Neuroepidemiol Sect, Bethesda, MD 20892 USA. RP Rianon, NJ (reprint author), UT Med Sch Houston, Dept Internal Med, Div Geriatr & Palliat Med, 6431 Fannin St MSB 5-118, Houston, TX 77030 USA. EM Nahid.J.Rianon@uth.tmc.edu RI Gudnason, Vilmundur/K-6885-2015; OI Gudnason, Vilmundur/0000-0001-5696-0084; Lang, Thomas/0000-0002-3720-8038 FU NIH [N01-AG-12100]; NIA Intramural Research Program, Hjartavernd (Icelandic Heart Association); Althingi (the Icelandic Parliament) FX The Age, Gene/Environment Susceptibility-Reykjavik Study is funded by NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). Genotyping was conducted at the NIA IRP Laboratory of Neurogenetics. The authors thank Faith Reidenbach, Caley-Reidenbach Consulting, LLP, for editorial assistance. NR 26 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1094-6950 EI 1559-0747 J9 J CLIN DENSITOM JI J. Clin. Densitom. PD JAN-MAR PY 2014 VL 17 IS 1 BP 25 EP 31 DI 10.1016/j.jocd.2013.03.005 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB2BP UT WOS:000331598300006 PM 23562129 ER PT J AU Riccetto, AGL Buzolin, M Fernandes, JF Traina, F Barjas-de-Castro, MLR Silva, MTN Oliveira, JB Vilela, MM AF Riccetto, A. G. L. Buzolin, M. Fernandes, J. F. Traina, F. Barjas-de-Castro, M. L. R. Silva, M. T. N. Oliveira, J. B. Vilela, M. M. TI Compound Heterozygous RAG2 Mutations Mimicking Hyper IgM Syndrome SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Letter ID GRANULOMATOUS-DISEASE; CLINICAL PHENOTYPES C1 [Riccetto, A. G. L.; Buzolin, M.; Silva, M. T. N.; Vilela, M. M.] Univ Estadual Campinas, Med Sch Unicamp, Ctr Invest Pediat CIPED, Dept Pediat, BR-13083887 Campinas, SP, Brazil. [Fernandes, J. F.] HIAE, Sao Paulo, Brazil. [Traina, F.; Barjas-de-Castro, M. L. R.] Univ Estadual Campinas, Med Sch Unicamp, Hematol & Hemotherapy Ctr, BR-13083887 Campinas, SP, Brazil. [Oliveira, J. B.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Vilela, MM (reprint author), Univ Estadual Campinas, Med Sch Unicamp, Ctr Invest Pediat CIPED, Dept Pediat, Rua Tessalia Vieira de Camargo 126, BR-13083887 Campinas, SP, Brazil. EM marluce@fcm.unicamp.br RI Vilela, Maria Marluce /G-3916-2013; Traina, Fabiola/L-3809-2014 FU Intramural NIH HHS NR 6 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD JAN PY 2014 VL 34 IS 1 BP 7 EP 9 DI 10.1007/s10875-013-9956-4 PG 3 WC Immunology SC Immunology GA AB7HW UT WOS:000331961400003 PM 24174341 ER PT J AU Ramirez, JL Garver, LS Brayner, FA Alves, LC Rodrigues, J Molina-Cruz, A Barillas-Mury, C AF Ramirez, Jose Luis Garver, Lindsey S. Brayner, Fabio Andre Alves, Luiz Carlos Rodrigues, Janneth Molina-Cruz, Alvaro Barillas-Mury, Carolina TI The Role of Hemocytes in Anopheles gambiae Antiplasmodial Immunity SO JOURNAL OF INNATE IMMUNITY LA English DT Article DE Hemocyte differentiation; Plasmodium; Malaria; Immune priming ID HUMAN MALARIA PARASITE; LARVAL HEMATOPOIESIS; AEDES-AEGYPTI; PLASMODIUM; DROSOPHILA; MOSQUITOS; DIFFERENTIATION; INFECTION; RESPONSES; PATHWAYS AB Hemocytes synthesize key components of the mosquito complement-like system, but their role in the activation of antiplasmodial responses has not been established. The effect of activating Toll signaling in hemocytes on Plasmodium survival was investigated by transferring hemocytes or cell-free hemolymph from donor mosquitoes in which the suppressor cactus was silenced. These transfers greatly enhanced antiplasmodial immunity, indicating that hemocytes are active players in the activation of the complement-like system, through an effector/effectors regulated by the Toll pathway. A comparative analysis of hemocyte populations between susceptible G3 and the refractory L3-5 Anopheles gambiae mosquito strains did not reveal significant differences under basal conditions or in response to Plasmodium berghei infection. The response of susceptible mosquitoes to different Plasmodium species revealed similar kinetics following infection with P. berghei, P. yoelii or P. falciparum, but the strength of the priming response was stronger in less compatible mosquito-parasite pairs. The Toll, Imd, STAT or JNK signaling cascades were not essential for the production of the hemocyte differentiation factor (HDF) in response to P. berghei infection, but disruption of Toll, STAT or JNK abolished hemocyte differentiation in response to HDF. We conclude that hemocytes are key mediators of A. gambiae antiplasmodial responses. (C) 2013 S. Karger AG, Basel C1 [Ramirez, Jose Luis; Garver, Lindsey S.; Brayner, Fabio Andre; Alves, Luiz Carlos; Rodrigues, Janneth; Molina-Cruz, Alvaro; Barillas-Mury, Carolina] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Rodrigues, Janneth] GlaxoSmithKline GSK, Tres Cantos, Spain. RP Barillas-Mury, C (reprint author), Lab Malaria & Vector Res, Mosquito Immun & Vector Competence Sect, NIH, 12735 Twinbrook Pkwy,Room 2E-20C, Rockville, MD 20852 USA. EM cbarillas@niaid.nih.gov OI Garver, Lindsey/0000-0003-2893-0130 FU Brazilian National Council for the Development of Science and Technology; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior of the Brazilian Ministry of Education; Intramural National Institute of Allergy and Infectious Diseases Research Opportunities program; Malaria Infection Biology program, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank A. Laughinghouse and K. Lee for insectary support. This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. F.A. Brayner received funding from the Brazilian National Council for the Development of Science and Technology, L.C. Alves from the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior of the Brazilian Ministry of Education, J.L. Ramirez from the Intramural National Institute of Allergy and Infectious Diseases Research Opportunities program and L.S. Graver from the Malaria Infection Biology program, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 28 TC 21 Z9 22 U1 1 U2 12 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X EI 1662-8128 J9 J INNATE IMMUN JI J. Innate Immun. PY 2014 VL 6 IS 2 BP 119 EP 128 DI 10.1159/000353765 PG 10 WC Immunology SC Immunology GA AB4QL UT WOS:000331774900002 PM 23886925 ER PT J AU Mattson, MP AF Mattson, Mark P. TI Interventions that Improve Body and Brain Bioenergetics for Parkinson's Disease Risk Reduction and Therapy SO JOURNAL OF PARKINSONS DISEASE LA English DT Review DE Autonomic nervous system; autophagy; brainstem; exercise; GLP-1; insulin; intermittent fasting; mitochondrial biogenesis; synuclein ID GAMMA AGONIST PIOGLITAZONE; GLUCAGON-LIKE PEPTIDE-1; MOUSE MODEL; ALZHEIMERS-DISEASE; DIETARY RESTRICTION; CALORIC RESTRICTION; NEUROTROPHIC FACTOR; DOPAMINERGIC-NEURONS; INSULIN-RESISTANCE; PHYSICAL-ACTIVITY AB Studies of Parkinson's disease (PD) patients, animal models and pathogenic actions of genetic mutations that cause familial PD have established that neuronal bioenergetics are compromised with brainstem and midbrain monoaminergic neurons being particularly vulnerable. Peripheral insulin resistance and diabetes in midlife may increase the risk of PD, and diet and lifestyle changes that increase insulin sensitivity (exercise and intermittent energy restriction) can counteract neurodegenerative processes and improve functional outcome in animal models. Insulin sensitizing glucagon-like peptide 1 (GLP-1) analogs are beneficial in animal models of PD, and the results of an initial clinical trial in PD patients are promising. In addition to improving peripheral and brain energy metabolism, exercise, intermittent energy restriction and GLP-1 analogs may bolster neuronal adaptive stress response pathways that enhance neurotrophic signaling, DNA repair, proteostasis and mitochondrial biogenesis. C1 [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mark.mattson@nih.gov FU Intramural Research Program of the National Institute on Aging, NIH FX This work was supported by the Intramural Research Program of the National Institute on Aging, NIH. NR 145 TC 14 Z9 15 U1 5 U2 14 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 EI 1877-718X J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2014 VL 4 IS 1 BP 1 EP 13 DI 10.3233/JPD-130335 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AB5EA UT WOS:000331810500001 PM 24473219 ER PT J AU Biddie, SC John, S AF Biddie, Simon C. John, Sam TI Minireview: Conversing With Chromatin: The Language of Nuclear Receptors SO MOLECULAR ENDOCRINOLOGY LA English DT Review ID TRANSCRIPTION FACTOR-BINDING; EMBRYONIC STEM-CELLS; RNA-POLYMERASE-II; REGULATED GENE-EXPRESSION; COFFIN-SIRIS SYNDROME; O-GLCNAC TRANSFERASE; PPAR-GAMMA-RXR; GLUCOCORTICOID-RECEPTOR; REMODELING COMPLEX; HUMAN GENOME AB Nuclear receptors are transcription factors that are activated by physiological stimuli to bind DNA in the context of chromatin and regulate complex biological pathways. Major advances in nuclear receptor biology have been aided by genome scale examinations of receptor interactions with chromatin. In this review, we summarize the roles of the chromatin landscape in regulating nuclear receptor function. Chromatin acts as a central integrator in the nuclear receptor-signaling axis, operating in distinct temporal modalities. Chromatin effects nuclear receptor action by specifying its genomic localization and interactions with regulatory elements. On receptor binding, changes in chromatin operate as an effector of receptor signaling to modulate transcriptional events. Chromatin is therefore an integral component of the pathways that guide nuclear receptor action in cell-type-specific and cell state-dependent manners. C1 [Biddie, Simon C.] Cambridge Univ Hosp Natl Hlth Serv Fdn Trust, Addenbrookes Hosp, Cambridge CB2 0QQ, England. [John, Sam] NCI, NIH, Lab Genome Integr, Bethesda, MD 20892 USA. RP John, S (reprint author), NCI, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM Simon.Biddie@doctors.org.uk; sam@mail.nih.gov OI Biddie, Simon/0000-0002-8253-0253 FU National Institutes of Health FX This research was supported, in part, by the Intramural Research Program of the National Institutes of Health. NR 168 TC 4 Z9 4 U1 0 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JAN PY 2014 VL 28 IS 1 BP 3 EP 15 DI 10.1210/me.2013-1247 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB4ZS UT WOS:000331799300002 PM 24196351 ER PT J AU Lee, MR Cacic, K Demers, CH Haroon, M Heishman, S Hommer, DW Epstein, DH Ross, TJ Stein, EA Heilig, M Salmeron, BJ AF Lee, Mary R. Cacic, Kelsey Demers, Catherine H. Haroon, Maleeha Heishman, Stephen Hommer, Daniel W. Epstein, David H. Ross, Thomas J. Stein, Elliot A. Heilig, Markus Salmeron, Betty Jo TI Gender differences in neural-behavioral response to self-observation during a novel fMRI social stress task SO NEUROPSYCHOLOGIA LA English DT Article DE Trier Social Stress Test; Imaging; Stress; Social function; Social threat; fMRI ID INFERIOR FRONTAL-CORTEX; HPA AXIS RESPONSES; SEX-DIFFERENCES; MENSTRUAL-CYCLE; PSYCHOSOCIAL STRESS; EMOTIONAL STIMULI; ANTERIOR INSULA; BRAIN; INHIBITION; VULNERABILITY AB The neural correlates of response to psychosocial stress and gender differences therein are difficult to model experimentally as this type of stressor is difficult to induce in a brain imaging environment. The Trier Social Stress Test (TSST), a behavioral paradigm that reliably induces moderate levels of stress was thus modified for the MRI environment. To determine the neurobehavioral basis of gender differences in response to observing oneself under social evaluative stress, 26 subjects (14 females) performed the TSST while being videotaped. During fMRI scanning, subjects were shown alternating video clips of two CONDITIONS: SELF or a same-sex OTHER performing the TSST. Subjects rated their stress level immediately after the video clips. GENDER differences in the [SELF-OTHER] contrast were analyzed. There was a GENDER x CONDITION interaction such that only women reported increased subjective stress during video feedback of their TSST session. A whole brain analysis (SELF vs. OTHER) showed activation in the bilateral insula, inferior, middle and superior frontal gyri. Greater recruitment was seen among males in some of these same areas in the context of significantly lower stress ratings. Activation of areas involved in inhibitory control and sensory awareness might contribute to the significantly lower stress ratings in males. Understanding these gender differences is relevant to disorders of stress and self-concept. Published by Elsevier Ltd. C1 [Lee, Mary R.; Hommer, Daniel W.; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, Natl Inst Hlth, Bethesda, MD 20892 USA. [Cacic, Kelsey] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Demers, Catherine H.; Ross, Thomas J.; Stein, Elliot A.; Salmeron, Betty Jo] Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. [Haroon, Maleeha; Heishman, Stephen] Natl Inst Drug Abuse, Nicotine Psychopharmacol Sect, Intramural Res Program, Baltimore, MD 21224 USA. [Epstein, David H.] Natl Inst Drug Abuse, Clin Pharmacol & Therapeut Res Branch, Treatment Sect, Intramural Res Program, Baltimore, MD 21224 USA. RP Lee, MR (reprint author), 10 Ctr Dr,10-CRC,Room 1-5330, Bethesda, MD USA. EM leemary@mail.nih.gov RI Salmeron, Betty Jo/M-1793-2016; OI Salmeron, Betty Jo/0000-0003-1699-9333; Heilig, Markus/0000-0003-2706-2482; Ross, Thomas/0000-0002-7745-3572 FU Intramural Research Program of the National Institute on Drug Abuse FX This work was supported by the Intramural Research Program of the National Institute on Drug Abuse. NR 40 TC 7 Z9 8 U1 1 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JAN PY 2014 VL 53 BP 257 EP 263 DI 10.1016/j.neuropsychologia.2013.11.022 PG 7 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA AB3AG UT WOS:000331663100027 PM 24316200 ER PT J AU Kamel, F Goldman, SM Umbach, DM Chen, HL Richardson, G Barber, MR Meng, C Marras, C Korell, M Kasten, M Hoppin, JA Comyns, K Chade, A Blair, A Bhudhikanok, GS Ross, GW Langston, JW Sandler, DP Tanner, CM AF Kamel, Freya Goldman, Samuel M. Umbach, David M. Chen, Honglei Richardson, Gina Barber, Marie Richards Meng, Cheryl Marras, Connie Korell, Monica Kasten, Meike Hoppin, Jane A. Comyns, Kathleen Chade, Anabel Blair, Aaron Bhudhikanok, Grace S. Ross, G. Webster Langston, J. William Sandler, Dale P. Tanner, Caroline M. TI Dietary fat intake, pesticide use, and Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; Dietary fat; Polyunsaturated fatty acids; Pesticides ID MOUSE MODEL; RISK; DEGENERATION; NEUROTOXICITY; ACIDS AB Background: Dietary fat intake may modify Parkinson's disease (PD) risk directly or by altering the response to environmental neurotoxicants including pesticides. Methods: We conducted a case-control study of PD nested in the Agricultural Health Study (AHS), a cohort of pesticide applicators and spouses. We evaluated diet and pesticide use before diagnosis in 89 PD cases, confirmed by movement disorder specialists, or a corresponding date in 336 frequency-matched controls. Associations were evaluated using multivariate logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: In the AHS, PD was inversely associated with N-3 polyunsaturated fatty acids (PUFAs) (OR 0.4, 95% CI 0.2-0.8 for highest vs. lowest tertile) and the N-3 precursor alpha-linolenic acid (0.4, 0.2-0.8). In a meta-analysis of nine studies, including the present one, PD was inversely associated with a-linolenic acid (0.81, 0.68-0.96). In the AHS, associations of PD with the pesticides paraquat and rotenone were modified by fat intake. The OR for paraquat was 4.2 (1.5-12) in individuals with PUFA intake below the median but 1.2 (0.4-3.4) in those with higher intake (p-interaction = 0.10). The OR for rotenone was 5.8 (2.3-15) in those with saturated fat intake above the median but 1.5 (0.5-4.2) in those with lower intake (p-interaction = 0.02). Conclusions: PUFA intake was consistently associated with lower PD risk, and dietary fats modified the association of PD risk with pesticide exposure. If confirmed, these findings suggest that a diet high in PUFAs and low in saturated fats might reduce risk of PD. Published by Elsevier Ltd. C1 [Kamel, Freya; Chen, Honglei; Richardson, Gina; Hoppin, Jane A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Goldman, Samuel M.; Meng, Cheryl; Korell, Monica; Comyns, Kathleen; Bhudhikanok, Grace S.; Langston, J. William; Tanner, Caroline M.] Parkinsons Inst, Sunnyvale, CA USA. [Umbach, David M.] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Barber, Marie Richards] Westat Corp, Durham, NC USA. [Marras, Connie] Univ Toronto, Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. [Kasten, Meike] Univ Lubeck, Dept Neurol, Lubeck, Germany. [Kasten, Meike] Univ Lubeck, Dept Clin & Mol Neurogenet, Lubeck, Germany. [Chade, Anabel] Favaloro Univ, Inst Neurosci, Inst Cognit Neurol, Buenos Aires, DF, Argentina. [Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD USA. [Ross, G. Webster] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA. RP Kamel, F (reprint author), NIEHS, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM kamel@niehs.nih.gov RI Goldman, Samuel/A-2225-2014; OI Goldman, Samuel/0000-0002-3039-9927; Kamel, Freya/0000-0001-5052-6615; Chen, Honglei/0000-0003-3446-7779; Sandler, Dale/0000-0002-6776-0018 FU NIEHS [R01-ES10803]; Intramural Research Program of the National Institutes of Health (National Institute of Environmental Health Sciences) [Z01-ES044007, Z01-ES049030]; National Cancer Institute [Z01-CP010119] FX This research was supported by NIEHS grant R01-ES10803 and James and Sharron Clark and by the Intramural Research Program of the National Institutes of Health (National Institute of Environmental Health Sciences grants Z01-ES044007 and Z01-ES049030 and National Cancer Institute grant Z01-CP010119). NR 31 TC 23 Z9 23 U1 2 U2 24 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD JAN PY 2014 VL 20 IS 1 BP 82 EP 87 DI 10.1016/j.parkreldis.2013.09.023 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA AB0VU UT WOS:000331511000016 PM 24120951 ER PT J AU Prasad, V Cifu, A AF Prasad, Vinay Cifu, Adam TI Eliminating chronic kidney disease... as a diagnosis SO POLSKIE ARCHIWUM MEDYCYNY WEWNETRZNEJ-POLISH ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID CONVERTING ENZYME-INHIBITORS; NONDIABETIC RENAL-DISEASE; METAANALYSIS; PROGRESSION; TRIALS C1 [Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Cifu, Adam] Univ Chicago, Pritzker Sch Med, Dept Med, Gen Internal Med Sect, Chicago, IL 60637 USA. RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr 10-12N226, Bethesda, MD 20892 USA. EM vinayak.prasad@nih.gov NR 15 TC 3 Z9 3 U1 0 U2 1 PU MEDYCYNA PRAKTYCZNA PI KRAKOW PA UL KRAKOWSKA 41, KRAKOW, 31-066, POLAND SN 0032-3772 J9 POL ARCH MED WEWN JI Pol. Arch. Med. Wewn. PY 2014 VL 124 IS 1-2 BP 7 EP 9 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AB7BP UT WOS:000331944600002 PM 24531346 ER PT S AU Bornstein, MH AF Bornstein, Marc H. BE Fiske, ST TI Human Infancy ... and the Rest of the Lifespan SO ANNUAL REVIEW OF PSYCHOLOGY, VOL 65 SE Annual Review of Psychology LA English DT Review; Book Chapter DE infancy; infant effects; stability; prediction ID LOW-BIRTH-WEIGHT; MOTHER-CHILD INTERACTION; RISK PRETERM INFANTS; VOICE-ONSET TIME; AGE 8 YEARS; THAN 750 G; LANGUAGE-DEVELOPMENT; FOLLOW-UP; INDIVIDUAL-DIFFERENCES; INHIBITORY CONTROL AB Human infancy has been studied as a platform for hypothesis and theory testing, as a major physiological and psychological adjustment, as an object of adults' effects as well as a source of effects on adults, for its comparative value, as a stage of life, and as a setting point for the life course. Following an orientation to infancy studies, including previous reviews and a discussion of the special challenges infants pose to research, this article focuses on infancy as a foundation and catalyst of human development in the balance of the life course. Studies of stability and prediction from infancy illustrate the depth and complexity of modern research on infants and provide a long-awaited reply to key philosophical and practical questions about the meaningfulness and significance of infancy. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Publ Hlth Serv, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Publ Hlth Serv, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov FU Intramural NIH HHS NR 326 TC 16 Z9 16 U1 21 U2 84 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4308 BN 978-0-8243-0265-8 J9 ANNU REV PSYCHOL JI Annu. Rev. Psychol PY 2014 VL 65 BP 121 EP 158 DI 10.1146/annurev-psych-120710-100359 PG 38 WC Psychology; Psychology, Multidisciplinary SC Psychology GA BJR53 UT WOS:000329821700007 PM 24405360 ER PT S AU Blakemore, SJ Mills, KL AF Blakemore, Sarah-Jayne Mills, Kathryn L. BE Fiske, ST TI Is Adolescence a Sensitive Period for Sociocultural Processing? SO ANNUAL REVIEW OF PSYCHOLOGY, VOL 65 SE Annual Review of Psychology LA English DT Review; Book Chapter DE social cognition; mentalizing; adolescent brain development; risk taking; plasticity; sensitive period ID AGE-RELATED DIFFERENCES; FUZZY-TRACE THEORY; SOCIAL BRAIN; DECISION-MAKING; DEVELOPMENTAL-CHANGES; PREFRONTAL CORTEX; PEER REJECTION; RISK-TAKING; LATE CHILDHOOD; GAMBLING TASK AB Adolescence is a period of formative biological and social transition. Social cognitive processes involved in navigating increasingly complex and intimate relationships continue to develop throughout adolescence. Here, we describe the functional and structural changes occurring in the brain during this period of life and how they relate to navigating the social environment. Areas of the social brain undergo both structural changes and functional reorganization during the second decade of life, possibly reflecting a sensitive period for adapting to one's social environment. The changes in social environment that occur during adolescence might interact with increasing executive functions and heightened social sensitivity to influence a number of adolescent behaviors. We discuss the importance of considering the social environment and social rewards in research on adolescent cognition and behavior. Finally, we speculate about the potential implications of this research for society. C1 [Blakemore, Sarah-Jayne; Mills, Kathryn L.] UCL, Inst Cognit Neurosci, London WC1N 3HT, England. [Mills, Kathryn L.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Blakemore, SJ (reprint author), UCL, Inst Cognit Neurosci, London WC1N 3HT, England. EM s.blakemore@ucl.ac.uk NR 124 TC 106 Z9 108 U1 29 U2 109 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4308 BN 978-0-8243-0265-8 J9 ANNU REV PSYCHOL JI Annu. Rev. Psychol PY 2014 VL 65 BP 187 EP 207 DI 10.1146/annurev-psych-010213-115202 PG 21 WC Psychology; Psychology, Multidisciplinary SC Psychology GA BJR53 UT WOS:000329821700009 PM 24016274 ER PT J AU Bowen, RAR Remaley, AT AF Bowen, Raffick A. R. Remaley, Alan T. TI Interferences from blood collection tube components on clinical chemistry assays SO BIOCHEMIA MEDICA LA English DT Review DE blood collection devices; blood collection sample tube; clinical assays; clinical chemistry; interference; pre-analytical; surfactant ID SERUM-SEPARATOR TUBES; SAMPLING TUBES; TOTAL TRIIODOTHYRONINE; HEMODIALYSIS-PATIENTS; COAGULATION ASSAYS; VACUTAINER TUBES; CLOT ACTIVATOR; PLASMA; DEVICES; QUALITY AB Improper design or use of blood collection devices can adversely affect the accuracy of laboratory test results. Vascular access devices, such as catheters and needles, exert shear forces during blood flow, which creates a predisposition to cell lysis. Components from blood collection tubes, such as stoppers, lubricants, surfactants, and separator gels, can leach into specimens and/or adsorb analytes from a specimen; special tube additives may also alter analyte stability. Because of these interactions with blood specimens, blood collection devices are a potential source of pre-analytical error in laboratory testing. Accurate laboratory testing requires an understanding of the complex interactions between collection devices and blood specimens. Manufacturers, vendors, and clinical laboratorians must consider the pre-analytical challenges in laboratory testing. Although other authors have described the effects of endogenous substances on clinical assay results, the effects/impact of blood collection tube additives and components have not been well systematically described or explained. This review aims to identify and describe blood collection tube additives and their components and the strategies used to minimize their effects on clinical chemistry assays. C1 [Bowen, Raffick A. R.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. [Remaley, Alan T.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Bowen, RAR (reprint author), Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. EM rbowen@stanfordmed.org NR 98 TC 33 Z9 35 U1 4 U2 29 PU CROATIAN SOC MEDICAL BIOCHEMISTS PI ZAGREB PA DOMAGOJEVA 2, ZAGREB, 10000, CROATIA SN 1330-0962 EI 1846-7482 J9 BIOCHEM MEDICA JI Biochem. Medica. PY 2014 VL 24 IS 1 BP 31 EP 44 PG 14 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AA7IB UT WOS:000331269800007 PM 24627713 ER PT J AU Huang, Q Yu, L Levine, AJ Nussinov, R Ma, B AF Huang, Qiang Yu, Long Levine, Arnold J. Nussinov, Ruth Ma, Buyong TI Dipeptide analysis of p53 mutations and evolution of p53 family proteins SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article DE p53/p63/p73; Gene regulation; Phosphorylation; Cancer; Mutation; Evolution ID TUMOR-SUPPRESSOR P53; MUTANT P53; DNA-BINDING; AMINO-ACID; FOLDING FUNNELS; CANCER; GAIN; P63; APOPTOSIS; P73 AB p53 gain-of-function mutations are similar to driver mutations in cancer genes, with both promoting tumorigenesis. Most previous studies focused on residues lost by mutations, providing information related to a dominantly-negative effect. However, to understand gain-of-function mutations, it is also important to investigate what are the distributions of residues gained by mutations. We compile available p53/p63/p73 protein sequences and construct a non-redundant dataset We analyze the amino acid and dipeptide composition of p53/p63/p73 proteins across evolution and compare them with the gain/loss of amino acids and dipeptides in human p53 following cancer-related somatic mutations. We find that the ratios of amino acids gained via somatic mutations during evolution to those lost through p53 cancer mutations correlate with the ratios found in single nucleotide polymorphisms in the human proteome. The dipeptide mutational gain/loss ratios are inversely correlated with those observed over p53 evolution but tend to follow the increasing p63/p73-like dipeptide propensities. We successfully simulated the p53 cancer mutation spectrum using the dipeptide composition across the p53 family accounting for the likelihood of mutations in p53 codons. The results revealed that the p53 mutation spectrum is dominated not only by p53 evolution but also by reversal of evolution to a certain degree. This article is part of a Special Issue entitled: Computational Proteomics, Systems Biology & Clinical Implications. Guest Editor: Yudong Cal. (C) 2013 Elsevier B.V. All rights reserved. C1 [Huang, Qiang; Yu, Long] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. [Levine, Arnold J.] Inst Adv Study, Simons Ctr Syst Biol, Princeton, NJ 08540 USA. [Nussinov, Ruth; Ma, Buyong] NIH, Ctr Canc, Res Nanobiol Program, SAIC Frederick,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Ma, B (reprint author), NIH, Ctr Canc, Res Nanobiol Program, SAIC Frederick,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM mabuyong@mail.nih.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; National Natural Science Foundation of China [30570406, 30024001]; HI-tech Research and Development Program of China [2008AA02Z311]; National Key Sci-Tech Special Projects of China [2008ZX10002-020]; NCI; Verto Institute FX This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Huang and Yu were supported by grants from the National Natural Science Foundation of China (30570406, 30024001), the HI-tech Research and Development Program of China (2008AA02Z311), and the National Key Sci-Tech Special Projects of China (2008ZX10002-020). A. J. Levine thanks grants from the NCI and the Verto Institute. NR 63 TC 4 Z9 4 U1 1 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 EI 0006-3002 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD JAN PY 2014 VL 1844 IS 1 SI SI BP 198 EP 206 DI 10.1016/j.bbapap.2013.04.002 PN B PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AA2FW UT WOS:000330911500006 PM 23583620 ER PT J AU Mensah, GA Sampson, UKA AF Mensah, George A. Sampson, Uchechukwu K. A. TI Coronary Mortality in China Fence, Ambulance, or Hospital Treatments? SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Editorial Material DE Editorials; cardiovascular diseases; China; coronary disease; decision modeling; prevention and control ID HEART-DISEASE MORTALITY; RISK-FACTOR CHANGES; CARDIOVASCULAR-DISEASE; POLICY MODEL; DECLINE; DEATHS; DECREASE; IMPACT; COST C1 [Mensah, George A.] NHLBI, NIH, Bethesda, MD 20892 USA. [Sampson, Uchechukwu K. A.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. RP Mensah, GA (reprint author), NIH, 31 Ctr Dr MSC 2486, Bethesda, MD 20892 USA. EM george.mensah@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 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2014 VL 7 IS 1 BP 8 EP 10 DI 10.1161/CIRCOUTCOMES.113.000761 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA4MY UT WOS:000331071200003 PM 24425711 ER PT J AU Escolar, E Lamas, GA Mark, DB Boineau, R Goertz, C Rosenberg, Y Nahin, RL Ouyang, P Rozema, T Magaziner, A Nahas, R Lewis, EF Lindblad, L Lee, KL AF Escolar, Esteban Lamas, Gervasio A. Mark, Daniel B. Boineau, Robin Goertz, Christine Rosenberg, Yves Nahin, Richard L. Ouyang, Pamela Rozema, Theodore Magaziner, Allan Nahas, Richard Lewis, Eldrin F. Lindblad, Lauren Lee, Kerry L. TI The Effect of an EDTA-based Chelation Regimen on Patients With Diabetes Mellitus and Prior Myocardial Infarction in the Trial to Assess Chelation Therapy (TACT) SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Editorial Material DE diabetes mellitus; myocardial infarction; secondary prevention ID GLYCATION END-PRODUCTS; LEAD; COMPLICATIONS; EXPOSURE; CADMIUM; DISEASE; ATHEROSCLEROSIS; NEPHROPATHY; PROGRESSION; INHIBITORS AB Background The Trial to Assess Chelation Therapy (TACT) showed clinical benefit of an EDTA-based infusion regimen in patients aged 50 years with prior myocardial infarction. Diabetes mellitus before enrollment was a prespecified subgroup. Methods and Results Patients received 40 infusions of EDTA chelation or placebo. A total of 633 (37%) patients had diabetes mellitus (322 EDTA and 311 placebo). EDTA reduced the primary end point (death, reinfarction, stroke, coronary revascularization, or hospitalization for angina; 25% versus 38%; hazard ratio, 0.59; 95% confidence interval [CI], 0.44-0.79; P<0.001) over 5 years. The result remained significant after Bonferroni adjustment for multiple subgroups (99.4% CI, 0.39-0.88; adjusted P=0.002). All-cause mortality was reduced by EDTA chelation (10% versus 16%; hazard ratio, 0.57; 95% CI, 0.36-0.88; P=0.011), as was the secondary end point (cardiovascular death, reinfarction, or stroke; 11% versus 17%; hazard ratio, 0.60; 95% CI, 0.39-0.91; P=0.017). However, after adjusting for multiple subgroups, those results were no longer significant. The number needed to treat to reduce 1 primary end point over 5 years was 6.5 (95% CI, 4.4-12.7). There was no reduction in events in non-diabetes mellitus (n=1075; P=0.877), resulting in a treatment by diabetes mellitus interaction (P=0.004). Conclusions Post-myocardial infarction patients with diabetes mellitus aged 50 demonstrated a marked reduction in cardiovascular events with EDTA chelation. These findings support efforts to replicate these findings and define the mechanisms of benefit. However, they do not constitute sufficient evidence to indicate the routine use of chelation therapy for all post-myocardial infarction patients with diabetes mellitus. C1 [Escolar, Esteban; Lamas, Gervasio A.] Columbia Univ, Mt Sinai Med Ctr, Div Cardiol, Miami Beach, FL 33140 USA. [Boineau, Robin; Rosenberg, Yves] NHLBI, Bethesda, MD 20892 USA. [Goertz, Christine] Palmer Ctr Chiropract Res, Davenport, IA USA. [Nahin, Richard L.] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. [Ouyang, Pamela] Johns Hopkins Univ, Baltimore, MD USA. [Rozema, Theodore] Biogenesis Med Ctr, Landrum, SC USA. [Magaziner, Allan] Magaziner Ctr Wellness, Cherry Hill, NJ USA. [Nahas, Richard] Seekers Ctr Integrat Med, Ottawa, ON, Canada. [Lewis, Eldrin F.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lewis, Eldrin F.] Harvard Univ, Sch Med, Boston, MA USA. [Mark, Daniel B.; Lindblad, Lauren; Lee, Kerry L.] Duke Clin Res Inst, Durham, NC USA. RP Lamas, GA (reprint author), Columbia Univ, Mt Sinai Med Ctr, Div Cardiol, 4300 Alton Rd,Suite 2070A, Miami Beach, FL 33140 USA. EM gervasio.lamas@msmc.com OI Nahin, Richard/0000-0002-3682-4816; Mark, Daniel/0000-0001-6340-8087; Nahas, Richard/0000-0002-9054-4401 FU NCCIH NIH HHS [U01 AT001156, U01AT001156]; NHLBI NIH HHS [U01 HL092607, U01HL092607] NR 32 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2014 VL 7 IS 1 BP 15 EP 24 DI 10.1161/CIRCOUTCOMES.113.000663 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA4MY UT WOS:000331071200006 PM 24254885 ER PT J AU Hlatky, MA Ray, RM Burwen, DR Margolis, KL Johnson, KC Kucharska-Newton, A Manson, JE Robinson, JG Safford, MM Allison, M Assimes, TL Bavry, AA Berger, J Cooper-DeHoff, RM Heckbert, SR Li, WJ Liu, SM Martin, LW Perez, MV Tindle, HA Winkelmayer, WC Stefanick, ML AF Hlatky, Mark A. Ray, Roberta M. Burwen, Dale R. Margolis, Karen L. Johnson, Karen C. Kucharska-Newton, Anna Manson, JoAnn E. Robinson, Jennifer G. Safford, Monika M. Allison, Matthew Assimes, Themistocles L. Bavry, Anthony A. Berger, Jeffrey Cooper-DeHoff, Rhonda M. Heckbert, Susan R. Li, Wenjun Liu, Simin Martin, Lisa W. Perez, Marco V. Tindle, Hilary A. Winkelmayer, Wolfgang C. Stefanick, Marcia L. TI Use of Medicare Data to Identify Coronary Heart Disease Outcomes in the Women's Health Initiative SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE myocardial infarction; patient outcome assessment; pragmatic clinical trials; randomized controlled trials; validation studies ID ACUTE MYOCARDIAL-INFARCTION; CLINICAL EVENTS COMMITTEE; POSITIVE PREDICTIVE-VALUE; END-POINTS; LINKING; TRIAL; ADJUDICATION; TRENDS; DIAGNOSIS; ESTROGEN AB Background Data collected as part of routine clinical practice could be used to detect cardiovascular outcomes in pragmatic clinical trials or clinical registry studies. The reliability of claims data for documenting outcomes is unknown. Methods and Results We linked records of Women's Health Initiative (WHI) participants aged 65 years to Medicare claims data and compared hospitalizations that had diagnosis codes for acute myocardial infarction or coronary revascularization with WHI outcomes adjudicated by study physicians. We then compared the hazard ratios for active versus placebo hormone therapy based solely on WHI-adjudicated events with corresponding hazard ratios based solely on claims data for the same hormone trial participants. Agreement between WHI-adjudicated outcomes and Medicare claims was good for the diagnosis of myocardial infarction (, 0.71-0.74) and excellent for coronary revascularization (, 0.88-0.91). The hormone:placebo hazard ratio for clinical myocardial infarction was 1.31 (95% confidence interval, 1.03-1.67) based on WHI outcomes and 1.29 (95% confidence interval, 1.00-1.68) based on Medicare data. The hazard ratio for coronary revascularization was 1.09 (95% confidence interval, 0.88-1.35) based on WHI outcomes and 1.10 (95% confidence interval, 0.89-1.35) based on Medicare data. The differences between hazard ratios derived from WHI and Medicare data were not significant in 1000 bootstrap replications. Conclusions Medicare claims may provide useful data on coronary heart disease outcomes among patients aged 65 years in clinical research studies. Clinical Trials Registration Information URL: www.clinicaltrials.gov. Unique identifier: NCT00000611. C1 [Hlatky, Mark A.; Assimes, Themistocles L.; Perez, Marco V.; Winkelmayer, Wolfgang C.; Stefanick, Marcia L.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Ray, Roberta M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Burwen, Dale R.] NHLBI, Bethesda, MD 20892 USA. [Margolis, Karen L.] HealthPartners Inst Educ & Res Fdn, Minneapolis, MN USA. [Johnson, Karen C.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Kucharska-Newton, Anna] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Manson, JoAnn E.] Harvard Univ, Sch Med, Boston, MA USA. [Robinson, Jennifer G.] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. [Safford, Monika M.] Univ Alabama Birmingham, Birmingham, AL USA. [Allison, Matthew] Univ Calif San Diego, San Diego, CA 92103 USA. [Bavry, Anthony A.; Cooper-DeHoff, Rhonda M.] Univ Florida, Gainesville, FL USA. [Berger, Jeffrey] NYU, Med Ctr, New York, NY 10016 USA. [Heckbert, Susan R.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Li, Wenjun] Univ Massachusetts, Sch Med, Worcester, MA USA. [Liu, Simin] Univ Calif Los Angeles, Los Angeles, CA USA. [Martin, Lisa W.] George Washington Univ, Washington, DC USA. [Tindle, Hilary A.] Univ Pittsburgh, Pittsburgh, PA USA. RP Hlatky, MA (reprint author), Stanford Univ, Sch Med, HRP Redwood Bldg,Room T150,259 Campus Dr, Stanford, CA 94305 USA. EM hlatky@stanford.edu RI Liu, Simin/I-3689-2014; Li, Wenjun/F-5634-2015; OI Liu, Simin/0000-0003-2098-3844; Li, Wenjun/0000-0001-5335-7386; Martin, Lisa Warsinger/0000-0003-4352-0914; Allison, Matthew/0000-0003-0777-8272; Assimes, Themistocles/0000-0003-2349-0009 FU National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C] FX The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 18 TC 26 Z9 26 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2014 VL 7 IS 1 BP 157 EP 162 DI 10.1161/CIRCOUTCOMES.113.000373 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA4MY UT WOS:000331071200022 PM 24399330 ER PT J AU Marti, CN Khan, H Mann, DL Georgiopoulou, VV Bibbins-Domingo, K Harris, T Koster, A Newman, A Kritchevsky, SB Kalogeropoulos, AP Butler, J AF Marti, Catherine N. Khan, Hassan Mann, Douglas L. Georgiopoulou, Vasiliki V. Bibbins-Domingo, Kirsten Harris, Tamara Koster, Annemarie Newman, Anne Kritchevsky, Stephen B. Kalogeropoulos, Andreas P. Butler, Javed CA Hlth ABC Study TI Soluble Tumor Necrosis Factor Receptors and Heart Failure Risk in Older Adults Health, Aging, and Body Composition (Health ABC) Study SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; inflammation; tumor necrosis factor-alpha ID PATHOPHYSIOLOGICALLY RELEVANT CONCENTRATIONS; LEFT-VENTRICULAR DYSFUNCTION; TNF-ALPHA; INFLAMMATORY MARKERS; CYTOKINE RECEPTORS; CIRCULATING LEVELS; EJECTION FRACTION; SERUM-LEVELS; DISEASE; MECHANISMS AB Background Tumor necrosis factor (TNF) levels are associated with risk for heart failure (HF). The soluble TNF type 1 (sTNF-R1) and type 2 (sTNF-R2) receptors are elevated in patients with manifest HF, but whether they are associated with risk for incident HF is unclear. Methods and Results Using Cox proportional hazard models, we examined the association between baseline levels of sTNF-R1 and sTNF-R2 with incident HF risk among 1285 participants of the Health, Aging, and Body Composition Study (age, 74.02.9 years; 51.4% women; 41.1% black). At baseline, median (interquartile range) of TNF, sTNF-R1, and sTNF-R2 levels was 3.14 (2.42-4.06), 1.46 (1.25-1.76), and 3.43 (2.95-4.02) ng/mL, respectively. During a median follow-up of 11.4 (6.9-11.7) years, 233 (18.1%) participants developed HF. In models controlling for other HF risk factors, TNF (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.02-1.61 per log(2) increase) and sTNF-R1 (HR, 1.68; 95% CI, 1.15-2.46 per log(2) increase), but not sTNF-R2 (HR, 1.15; 95% CI, 0.80-1.63 per log(2) increase), were associated with a higher risk for HF. These associations were consistent across whites and blacks (TNF, sTNF-R1, sTNF-R2; interaction P=0.531, 0.091, and 0.795, respectively) and in both sexes (TNF, sTNF-R1, sTNF-R2; interaction P=0.491, 0.672, and 0.999, respectively). TNF-R1 was associated with a higher risk for HF with preserved versus reduced ejection fraction (HR, 1.81; 95% CI, 1.03-3.18; P=0.038 for preserved versus HR, 0.90; 95% CI, 0.56-1.44; P=0.667 for reduced ejection fraction; interaction P=0.05). Conclusions In older adults, elevated levels of sTNF-R1 are associated with increased risk for incident HF. However, addition of TNF-R1 to the previously validated Health ABC HF risk model did not demonstrate material improvement in net discrimination or reclassification. C1 [Marti, Catherine N.; Georgiopoulou, Vasiliki V.; Kalogeropoulos, Andreas P.; Butler, Javed] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. [Khan, Hassan] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England. [Mann, Douglas L.] Washington Univ, Div Cardiol, St Louis, MO USA. [Bibbins-Domingo, Kirsten] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Harris, Tamara] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Koster, Annemarie] Maastricht Univ, Dept Social Med, CAPHRI, Sch Publ Hlth & Primary Care, Maastricht, Netherlands. [Newman, Anne] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Newman, Anne] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Kritchevsky, Stephen B.] Wake Forest Sch Med, Sect Gerontol & Geriatr Med, Winston Salem, NC USA. RP Butler, J (reprint author), Emory Clin Cardiovasc Res Inst, 1462 Clifton Rd,Suite 504, Atlanta, GA 30322 USA. EM javed.butler@emory.edu RI Kalogeropoulos, Andreas/A-9494-2009; Koster, Annemarie/E-7438-2010; Newman, Anne/C-6408-2013 OI Kalogeropoulos, Andreas/0000-0002-1284-429X; Mann, Douglas /0000-0002-2516-0145; Newman, Anne/0000-0002-0106-1150 FU National Institutes of Health, National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; National Institutes of Health, National Institute of Nursing Research [R01-NR012459]; National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR000454] FX This study was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging, and contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA grant R01-AG028050 and National Institute of Nursing Research grant R01-NR012459; and by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR000454. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 41 TC 15 Z9 15 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2014 VL 7 IS 1 BP 5 EP 11 DI 10.1161/CIRCHEARTFAILURE.113.000344 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA4ND UT WOS:000331071800002 PM 24323631 ER PT J AU Shah, AM Shah, SJ Anand, IS Sweitzer, NK O'Meara, E Heitner, JF Sopko, G Li, GC Assmann, SF McKinlay, SM Pitt, B Pfeffer, MA Solomon, SD AF Shah, Amil M. Shah, Sanjiv J. Anand, Inder S. Sweitzer, Nancy K. O'Meara, Eileen Heitner, John F. Sopko, George Li, Guichu Assmann, Susan F. McKinlay, Sonja M. Pitt, Bertram Pfeffer, Marc A. Solomon, Scott D. CA TOPCAT Investigators TI Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction Baseline Findings From the Echocardiographic Study of the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial SO CIRCULATION-HEART FAILURE LA English DT Article DE diastolic heart failure; echocardiography; heart failure; randomized controlled trial; spironolactone ID LEFT-VENTRICULAR HYPERTROPHY; RANDOMIZED CONTROLLED-TRIAL; MITRAL REGURGITATION; EUROPEAN-ASSOCIATION; DIASTOLIC FUNCTION; EXERCISE CAPACITY; SYSTOLIC FUNCTION; AMERICAN-SOCIETY; POPULATION; RECOMMENDATIONS AB Background Heart failure with preserved ejection fraction (HFpEF) is associated with substantial morbidity and mortality. Existing data on cardiac structure and function in HFpEF suggest significant heterogeneity in this population. Methods and Results Echocardiograms were obtained from 935 patients with HFpEF (left ventricular ejection fraction 45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial before initiation of randomized therapy. Average age was 7010 years, 49% were women, 14% were of African descent, and comorbidities were highly prevalent. Centralized quantitative analysis in a blinded core laboratory demonstrated a mean left ventricular ejection fraction of 59.37.9%, with prevalent concentric left ventricular remodeling (34%) and hypertrophy (43%), and left atrial enlargement (53%). Diastolic dysfunction was present in 66% of gradable participants and was significantly associated with greater left ventricular hypertrophy and a higher prevalence of left atrial enlargement. Doppler evidence of pulmonary hypertension was present in 36%. At least 1 measure of structural heart disease was present in 93% of patients. Conclusions Patients enrolled in TOPCAT demonstrated heterogeneous patterns of ventricular remodeling, with high prevalence of structural heart disease, including left ventricular hypertrophy and left atrial enlargement, in addition to pulmonary hypertension, each of which has been associated with adverse outcomes in HFpEF. Diastolic function was normal in approximately one third of gradable participants, highlighting the heterogeneity of the cardiac phenotype in this syndrome. These findings deepen our understanding of the TOPCAT trial population and expand our knowledge of the diversity of the cardiac phenotype in HFpEF. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302. C1 [Shah, Amil M.; Li, Guichu; Pfeffer, Marc A.; Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02445 USA. [Shah, Sanjiv J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Anand, Inder S.] VA Med Ctr, Minneapolis, MN USA. [Sweitzer, Nancy K.] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [O'Meara, Eileen] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Heitner, John F.] New York Methodist Hosp, Brooklyn, NY USA. [Sopko, George] NHLBI, Bethesda, MD 20892 USA. [Assmann, Susan F.; McKinlay, Sonja M.] New England Res Inst, Watertown, MA 02172 USA. [Pitt, Bertram] Univ Michigan, Sch Med, Ann Arbor, MI USA. RP Shah, AM (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02445 USA. EM ashah11@partners.org FU National Institutes of Health's National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD [N01 HC45207]; NHLBI [1K08HL116792-01A1] FX TOPCAT was funded by the National Institutes of Health's National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD, grant N01 HC45207. The work for this article was also supported by NHLBI grant 1K08HL116792-01A1 (to A. M. S.). NR 38 TC 52 Z9 56 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2014 VL 7 IS 1 BP 104 EP 115 DI 10.1161/CIRCHEARTFAILURE.113.000887 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA4ND UT WOS:000331071800014 PM 24249049 ER PT J AU LaBresh, KA Lazorick, S Ariza, AJ Furberg, RD Whetstone, L Hobbs, C de Jesus, J Bender, RH Salinas, IG Binns, HJ AF LaBresh, Kenneth A. Lazorick, Suzanne Ariza, Adolfo J. Furberg, Robert D. Whetstone, Lauren Hobbs, Connie de Jesus, Janet Bender, Randall H. Salinas, Ilse G. Binns, Helen J. TI Implementation of the NHLBI Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Rationale and study design for Young Hearts, Strong Starts, a cluster-randomized trial targeting body mass index, blood pressure, and tobacco SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Guideline implementation; Quality improvement; Cardiovascular disease; Prevention; Cluster randomized trial; Children ID CARE; DETERMINANTS; IMPROVEMENT; DISEASE AB Background: Cardiovascular disease (CVD) and the underlying atherosclerosis begin in childhood, and their presence and intensity are related to known cardiovascular disease risk factors. Attention to risk factor control in childhood has the potential to reduce subsequent risk of CVD. Objective: The Young Hearts Strong Starts Study was designed to test strategies facilitating adoption of the National, Heart, Lung and Blood Institute supported Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. This study compares guideline-based quality measures for body mass index, blood pressure, and tobacco using two strategies: a multifaceted, practice-directed intervention versus standard dissemination. Study Design: Two primary care research networks recruited practices and provided support for the intervention and outcome evaluations. Individual practices were randomly assigned to the intervention or control groups using a cluster randomized design based on network affiliation, number of clinicians per practice, urban versus nonurban location, and practice type. The units of observation are individual children because measure adherence is abstracted from individual patient's medical records. The units of randomization are physician practices. This results in a multilevel design in which patients are nested within practices. The intervention practices received toolkits and supported guideline implementation including academic detailing, an ongoing e-learning group. This project is aligned with the American Board of Pediatrics Maintenance of Certification requirements including monthly physician self-abstraction, webinars, and other elements of the trial. Significance: This trial will provide an opportunity to demonstrate tools and strategies to enhance CV prevention in children by guideline-based interventions. (C) 2013 Elsevier Inc. All rights reserved. C1 [LaBresh, Kenneth A.] RTI Int, Waltham, MA 02451 USA. [Lazorick, Suzanne; Whetstone, Lauren] E Carolina Univ, Brody Sch Med, Dept Pediat, Greenville, NC 27834 USA. [Lazorick, Suzanne; Whetstone, Lauren] E Carolina Univ, Brody Sch Med, Dept Publ Hlth, Greenville, NC 27834 USA. [Ariza, Adolfo J.; Salinas, Ilse G.; Binns, Helen J.] Ann & Robert H Lurie Childrens Hosp Chicago, Res Ctr, Mary Ann & J Milburn Smith Child Hlth Res Program, Pediat Practice Res Grp, Chicago, IL 60611 USA. [Furberg, Robert D.; Hobbs, Connie; Bender, Randall H.] RTI Int, Res Triangle Pk, NC 27709 USA. [de Jesus, Janet] NHLBI, Bethesda, MD 20892 USA. RP LaBresh, KA (reprint author), RTI Int, 1440 Main St, Waltham, MA 02451 USA. EM klabresh@rti.org; lazoricks@ecu.edu; aariza@luriechildrens.org; lauren.whetstone@cdph.ca.gov; dejesusjm@mail.nih.gov; ilse.salinas@northwestern.edu; hbinns@luriechildrens.org RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 FU National Heart, Lung, and Blood Institute [NHLBI-PB-(HL)-2009195D HHSN268200900120U] FX This study was funded by the National Heart, Lung, and Blood Institute, NHLBI-PB-(HL)-2009195D HHSN268200900120U. The sponsor participated in the design of the trial, and the decision to submit the article for publication, and reviewed the publication. NR 19 TC 3 Z9 3 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2014 VL 37 IS 1 BP 98 EP 105 DI 10.1016/j.cct.2013.11.011 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA AB0SC UT WOS:000331501400009 PM 24295879 ER PT J AU Simons-Morton, DG Chan, JC Kimel, AR Linz, PE Stowe, CL Summerson, J Ambrosius, WT AF Simons-Morton, Denise G. Chan, Jeffrey C. Kimel, Angela R. Linz, Peter E. Stowe, Cynthia L. Summerson, John Ambrosius, Walter T. TI Characteristics associated with informed consent for genetic studies in the ACCORD trial SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Genetics; Informed consent; Recruitment ID HYPERTENSION-ASSOCIATED TREATMENT; ALPHA-ADDUCIN POLYMORPHISM; TYPE-2 DIABETES-MELLITUS; HIGH BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; PERSONALIZED MEDICINE; PREVENTION; RISK; GENOTYPE; THERAPY AB Background: Prior studies found that some groups have lower genetic consent rates than others. Participant consent for genetic studies enables randomized trials to examine effects of interventions compared to control in participants with different genotypes. Methods: Unadjusted and multivariate associations between genetic consent rates and participant, study, and consent characteristics in 9573 participants approached for genetics consent in the multicenter Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which used a layered genetics consent. Results: Eighty-nine percent of eligible participants consented to genetic studies ("Any Consent") and 64.7% consented to studies of any genes by any investigator ("Full Consent"), with similar rates in randomized groups. Controlling for multiple characteristics, African-Americans had lower consent rates than others (Any Consent Odds Ratio, OR = 0.62, p = 0.0004; Full Consent OR = 0.67, p < 0.0001). Those with high school or higher education level had higher rates than less than high school graduates (Full Consent ORs 1.41-1.69, p-values < 0.0001). Consent rates were lower when genetics consent was separate from the main trial consent on the same day (Any Consent OR 030; Full Consent OR 0.52, p values < 0.0001) or on a subsequent day (Any Consent OR 0.70, p = 0.0022; Full Consent OR 0.76, p = 0.0002). Conclusion: High rates of consent for genetic studies can be obtained in complex randomized trials, with lower consent rates in African-Americans, in participants with less than high-school education, and for sharing samples with other investigators. A genetics consent separated from the main trial consent was associated with lower consent rates. Published by Elsevier Inc. C1 [Simons-Morton, Denise G.; Chan, Jeffrey C.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Kimel, Angela R.; Stowe, Cynthia L.; Summerson, John; Ambrosius, Walter T.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Linz, Peter E.] US Naval Hosp, Dept Cardiol, San Diego, CA 92134 USA. RP Simons-Morton, DG (reprint author), NIH, Off Dis Prevent, 6100 Execut Blvd,Suite 2B03,MSC 7523, Rockville, MD 20852 USA. EM simonsd@nih.gov; jeffreycchan@gmail.com; angiekimel@gmail.com; peter.linz@mercyships.org; cstowe@wakehealth.edu; jsummers@wakehealth.edu; wambrosi@wakehealth.edu FU National Heart, Lung, and Blood Institute [N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184]; IAA [Y1-HC-9035, Y1-HC-1010] FX This work was supported by National Heart, Lung, and Blood Institute contracts N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, and IAA #Y1-HC-9035 and IAA #Y1-HC-1010. The authors appreciate the contributions of Byron Hoogwerf and Stephen Giddings to the analysis plans for this paper. NR 26 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2014 VL 37 IS 1 BP 155 EP 164 DI 10.1016/j.cct.2013.12.002 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA AB0SC UT WOS:000331501400015 PM 24355197 ER PT J AU Hagberg, GE Mamedov, I Power, A Beyerlein, M Merkle, H Kiselev, VG Dhingra, K Kubicek, V Angelovski, G Logothetis, NK AF Hagberg, Gisela E. Mamedov, Ilgar Power, Anthony Beyerlein, Michael Merkle, Hellmut Kiselev, Valerij G. Dhingra, Kirti Kubicek, Vojtech Angelovski, Goran Logothetis, Nikos K. TI Diffusion properties of conventional and calcium-sensitive MRI contrast agents in the rat cerebral cortex SO CONTRAST MEDIA & MOLECULAR IMAGING LA English DT Article ID BRAIN EXTRACELLULAR-SPACE; HINDERED DIFFUSION; INFUSION; TISSUE; FLOW; OPTIMIZATION; TRANSPORT; SEQUENCE; SIGNAL; IONS C1 [Hagberg, Gisela E.; Mamedov, Ilgar; Power, Anthony; Beyerlein, Michael; Dhingra, Kirti; Angelovski, Goran; Logothetis, Nikos K.] Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, D-72076 Tubingen, Germany. [Merkle, Hellmut] NINDS, LFMI, NIH, Bethesda, MD 20892 USA. [Logothetis, Nikos K.] Univ Manchester, Manchester, Lancs, England. [Kiselev, Valerij G.] Univ Med Ctr, Dept Diagnost Radiol, Freiburg, Germany. [Kubicek, Vojtech] Charles Univ Prague, Fac Sci, Dept Inorgan Chem, Prague 12840, Czech Republic. RP Hagberg, GE (reprint author), Univ Hosp Tubingen & High Field Magnet Resonance, Max Planck Inst Biol Cybernet, Dept Radiol, Tubingen, Germany. EM gisela.hagberg@tuebingen.mpg.de RI Kiselev, Valerij/E-5535-2014; Hagberg, Gisela/A-2134-2010; Kubicek, Vojtech/I-6607-2016 OI Kiselev, Valerij/0000-0002-5349-5399; Hagberg, Gisela/0000-0003-2176-7086; Kubicek, Vojtech/0000-0003-0171-5713 FU Intramural Program of the NIH, National Institute Neurological Disorders and Stroke FX This research was supported in part by the Intramural Program of the NIH, National Institute Neurological Disorders and Stroke (HM). The authors would like to thank Murray Coles at the Max Planck Institute for Developmental Biology Tubingen for automatizing the T2 measurements. NR 40 TC 6 Z9 6 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1555-4309 EI 1555-4317 J9 CONTRAST MEDIA MOL I JI Contrast Media Mol. Imaging PD JAN PY 2014 VL 9 IS 1 SI SI BP 71 EP 82 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AA6DN UT WOS:000331189100008 PM 24470296 ER PT J AU Lomnicki, S Gullett, B Stoger, T Kennedy, I Diaz, J Dugas, TR Varner, K Carlin, DJ Dellinger, B Cormier, SA AF Lomnicki, Slawo Gullett, Brian Stoeger, Tobias Kennedy, Ian Diaz, Jim Dugas, Tammy R. Varner, Kurt Carlin, Danielle J. Dellinger, Barry Cormier, Stephania A. TI Combustion By-Products and Their Health Effects-Combustion Engineering and Global Health in the 21st Century: Issues and Challenges SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Review ID PARTICULATE AIR-POLLUTION; PERSISTENT FREE-RADICALS; DECREASE CARDIAC-FUNCTION; MOUSE MODEL; IN-VITRO; EXPOSURE; PARTICLES; INFLAMMATION; DYSFUNCTION; MORTALITY C1 [Lomnicki, Slawo; Dellinger, Barry] Louisiana State Univ, Dept Chem, Baton Rouge, LA 70803 USA. [Gullett, Brian] US EPA, Off Res & Dev, Res Triangle Pk, NC 27711 USA. [Stoeger, Tobias] Helmholtz Zent Rum Munchen, Oberschleissheim, Germany. [Kennedy, Ian] Univ Calif Davis, Dept Mech & Aerosp Engn, Davis, CA 95616 USA. [Diaz, Jim; Varner, Kurt] Louisiana State Univ, Dept Environm & Occupat Hlth Sci, Hlth Sci Ctr, New Orleans, LA USA. [Dugas, Tammy R.] Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol Toxicol & Neurosci, Shreveport, LA 71105 USA. [Carlin, Danielle J.] NIEHS, Superfund Res Program, Res Triangle Pk, NC 27709 USA. [Cormier, Stephania A.] Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. [Cormier, Stephania A.] Univ Tennessee, Ctr Hlth Sci, Dept Microbiol Immunol & Biochem, Memphis, TN 38163 USA. RP Cormier, SA (reprint author), Univ Tennessee, Hlth Sci Ctr, Childrens Res Fdn Inst, 50 N Dunlap, Memphis, TN 38103 USA. EM scormier@uthsc.edu RI Stoger, Tobias/M-9861-2014 OI Stoger, Tobias/0000-0002-2790-0389 FU NIEHS [P42ES013648, R13ES022854]; NSF [1060103] FX The author(s) received no financial support for the research, authorship, and/or publication of this article: The 13th congress was supported by funds from NIEHS (P42ES013648 to SL, TD, KV, and BD and SAC and R13ES022854 to BD) and NSF (1060103 to BD). NR 28 TC 1 Z9 1 U1 10 U2 29 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 EI 1092-874X J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN PY 2014 VL 33 IS 1 BP 3 EP 13 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA AA8UV UT WOS:000331371400001 PM 24434722 ER PT J AU Bordelon, NR Koester, AJ Arndt, TP Hong, SP Brys, AM Patton, KM Sutula, TP Joshi, PS Terse, PS AF Bordelon, N. R. Koester, A. J. Arndt, T. P. Hong, S. P. Brys, A. M. Patton, K. M. Sutula, T. P. Joshi, P. S. Terse, P. S. TI Subchronic Oral Toxicity Study of 2-Deoxy-D-Glucose (2-DG) in F344 Rats with a 15 Day Recovery Period SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-College-of-Toxicology CY NOV 03-06, 2013 CL San Antonio, TX SP Amer Coll Toxicol C1 [Joshi, P. S.; Terse, P. S.] NCATS, Bethesda, MD USA. [Sutula, T. P.] Univ Wisconsin, Madison, WI USA. [Bordelon, N. R.; Koester, A. J.; Arndt, T. P.; Hong, S. P.; Brys, A. M.; Patton, K. M.] Battelle Mem Inst, Columbus, OH 43201 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 EI 1092-874X J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN PY 2014 VL 33 IS 1 MA P520 BP 66 EP 66 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA AA8UV UT WOS:000331371400085 ER PT J AU Leibenluft, E AF Leibenluft, Ellen TI Categories and Dimensions, Brain and Behavior The Yins and Yangs of Psychopathology SO JAMA PSYCHIATRY LA English DT Editorial Material ID DISORDERS C1 NIMH, Sect Bipolar Spectrum Disorders, Div Intramural Res Programs, Dept Hlth & Human Serv,Emot & Dev Branch,NIH, Bethesda, MD 20892 USA. RP Leibenluft, E (reprint author), NIMH, Sect Bipolar Spectrum Disorders, Div Intramural Res Programs, Dept Hlth & Human Serv,Emot & Dev Branch,NIH, Bldg 15K,Room 210,MSC 2670, Bethesda, MD 20892 USA. EM leibs@mail.nih.gov NR 13 TC 1 Z9 1 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD JAN PY 2014 VL 71 IS 1 BP 15 EP 17 DI 10.1001/jamapsychiatry.2013.2810 PG 3 WC Psychiatry SC Psychiatry GA AA8UL UT WOS:000331370400003 PM 24285233 ER PT J AU Moeller, SJ Konova, AB Parvaz, MA Tomasi, D Lane, RD Fort, C Goldstein, RZ AF Moeller, Scott J. Konova, Anna B. Parvaz, Muhammad A. Tomasi, Dardo Lane, Richard D. Fort, Carolyn Goldstein, Rita Z. TI Functional, Structural, and Emotional Correlates of Impaired Insight in Cocaine Addiction SO JAMA PSYCHIATRY LA English DT Article ID ANTERIOR CINGULATE CORTEX; MEDIAL FRONTAL-CORTEX; VOXEL-BASED MORPHOMETRY; EVENT-RELATED FMRI; ERROR AWARENESS; GRAY-MATTER; INTEROCEPTIVE AWARENESS; MONETARY REWARD; DRUG-ADDICTION; BRAIN SYSTEMS AB IMPORTANCE Individuals with cocaine use disorder (CUD) have difficulty monitoring ongoing behavior, possibly stemming from dysfunction of brain regions mediating insight and self-awareness. OBJECTIVE To investigate the neural correlates of impaired insight in addiction using a combined functional magnetic resonance imaging and voxel-based morphometry approach. DESIGN, SETTING, AND PARTICIPANTS This multimodal imaging study was performed at the Clinical Research Center at Brookhaven National Laboratory. The study included 33 CUD cases and 20 healthy controls. MAIN OUTCOMES AND MEASURES Functional magnetic resonance imaging, voxel-based morphometry, Levels of Emotional Awareness Scale, and drug use variables. RESULTS Compared with the other 2 study groups, the impaired insight CUD group had lower error-induced rostral anterior cingulate cortex (rACC) activity as associated with more frequent cocaine use, less gray matter within the rACC, and lower Levels of Emotional Awareness Scale scores. CONCLUSIONS AND RELEVANCE These results point to rACC functional and structural abnormalities and diminished emotional awareness in a subpopulation of CUD cases characterized by impaired insight. Because the rACC has been implicated in appraising the affective and motivational significance of errors and other types of self-referential processing, functional and structural abnormalities in this region could result in lessened concern (frequently ascribed to minimization and denial) about behavioral outcomes that could potentially culminate in increased drug use. Treatments that target this CUD subgroup could focus on enhancing the salience of errors (eg, lapses). C1 [Moeller, Scott J.; Konova, Anna B.; Parvaz, Muhammad A.; Goldstein, Rita Z.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Konova, Anna B.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Tomasi, Dardo] NIAAA, Bethesda, MD USA. [Lane, Richard D.; Fort, Carolyn] Univ Arizona, Dept Psychiat, Tucson, AZ USA. RP Goldstein, RZ (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, One Gustave L Levy Pl,POB 1230, New York, NY 10029 USA. EM rita.goldstein@mssm.edu RI Tomasi, Dardo/J-2127-2015; Moeller, Scott/L-5549-2016; OI Moeller, Scott/0000-0002-4449-0844; Parvaz, Muhammad/0000-0002-2671-2327 FU National Institute on Drug Abuse [1R01DA023579, 1F32DA030017-01, 1F32DA033088] FX This research was supported by grants 1R01DA023579 (Dr Goldstein), 1F32DA030017-01 (Dr Moeller), and 1F32DA033088 (Dr Parvaz) from the National Institute on Drug Abuse. NR 91 TC 16 Z9 17 U1 3 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD JAN PY 2014 VL 71 IS 1 BP 61 EP 70 DI 10.1001/jamapsychiatry.2013.2833 PG 10 WC Psychiatry SC Psychiatry GA AA8UL UT WOS:000331370400010 PM 24258223 ER PT J AU Luger, TM Houston, TK Suls, J AF Luger, Tana M. Houston, Thomas K. Suls, Jerry TI Older Adult Experience of Online Diagnosis: Results From a Scenario-Based Think-Aloud Protocol SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE information seeking behavior; Internet; age factors ID HEALTH INFORMATION; SELF-REGULATION; INTERNET; WEB; QUESTIONNAIRE; STRATEGIES; BEHAVIOR; IMPACT; CARE AB Background: Searching for online information to interpret symptoms is an increasingly prevalent activity among patients, even among older adults. As older adults typically have complex health care needs, their risk of misinterpreting symptoms via online self-diagnosis may be greater. However, limited research has been conducted with older adults in the areas of symptom interpretation and human-computer interaction. Objective: The intent of the study was to describe the processes that a sample of older adults may use to diagnose symptoms online as well as the processes that predict accurate diagnosis. Methods: We conducted a series of "think-aloud" protocols with 79 adults aged 50 years or older. Participants received one of two vignettes that depicted symptoms of illness. Participants talked out loud about their thoughts and actions while attempting to diagnose the symptoms with and without the help of common Internet tools (Google and WebMD's Symptom Checker). Think-aloud content was categorized using an adapted Q-sort and general inductive approach. We then compared the think-aloud content of participants who were accurate in their diagnosis with those who were not. Results: Nineteen descriptive codes were identified from the think-aloud content. The codes touched upon Web navigation, attempts to organize and evaluate online health information, and strategies to diagnose symptoms. Participants most frequently relied on a strategy where they reviewed and then rejected the online diagnoses if they contained additional symptoms than those that were depicted in the vignette. Finally, participants who were inaccurate in their diagnosis reported being confused by the diagnosis task, lacking confidence in their diagnosis, and using their past experiences with illness to guide diagnosis more frequently than those participants who accurately diagnosed the symptoms. Conclusions: Older adult participants tended to rely on matching strategies to interpret symptoms, but many still utilized existing medical knowledge and previous illness experiences as a guide for diagnosis. Many participants also had difficulty navigating the Internet tools, which suggests an increased need for navigation aids in Web design. Furthermore, participants who were inaccurate in their diagnosis had more difficulty with the Internet tools and confusion with the task than those who were accurate. Future work in this area may want to utilize additional study design such as eye-tracking to further understand the coordination between Web navigation, online symptom information processing, and diagnostic strategies. C1 [Luger, Tana M.; Houston, Thomas K.] Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, Ehlth Qual Enhancement Res Initiat, Bedford, MA 01730 USA. [Houston, Thomas K.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Suls, Jerry] Natl Canc Inst, Behav Res Program, Bethesda, MD USA. RP Luger, TM (reprint author), Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, Ehlth Qual Enhancement Res Initiat, Bldg 70 152,200 Springs Rd, Bedford, MA 01730 USA. EM Tana.Luger2@va.gov NR 36 TC 7 Z9 7 U1 2 U2 14 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD JAN PY 2014 VL 16 IS 1 AR e16 DI 10.2196/jmir.2924 PG 12 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA AA9ZB UT WOS:000331450500010 PM 24434479 ER PT J AU Fries, JF Witter, J Rose, M Cella, D Khanna, D Morgan-DeWitt, E AF Fries, James F. Witter, James Rose, Matthias Cella, David Khanna, Dinesh Morgan-DeWitt, Esi TI Item Response Theory, Computerized Adaptive Testing, and PROMIS: Assessment of Physical Function SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE ITEM RESPONSE THEORY; COMPUTERIZED ADAPTIVE TESTING; PROMIS PHYSICAL FUNCTION; DISABILITY ID PATIENT-REPORTED OUTCOMES; INFORMATION-SYSTEM PROMIS; VALIDITY; RESPONSIVENESS; ARTHRITIS; SCALES AB Objective. Patient-reported outcome (PRO) questionnaires record health information directly from research participants because observers may not accurately represent the patient perspective. Patient-reported Outcomes Measurement Information System (PROMIS) is a US National Institutes of Health cooperative group charged with bringing PRO to a new level of precision and standardization across diseases by item development and use of item response theory (IRT). Methods. With IRT methods, improved items are calibrated on an underlying concept to form an item bank for a "domain" such as physical function (PF). The most informative items can be combined to construct efficient "instruments" such as 10-item or 20-item PF static forms. Each item is calibrated on the basis of the probability that a given person will respond at a given level, and the ability of the item to discriminate people from one another. Tailored forms may cover any desired level of the domain being measured. Computerized adaptive testing (CAT) selects the best items to sharpen the estimate of a person's functional ability, based on prior responses to earlier questions. PROMIS item banks have been improved with experience from several thousand items, and are calibrated on over 21,000 respondents. Results. In areas tested to date, PROMIS PF instruments are superior or equal to Health Assessment Questionnaire and Medical Outcome Study Short Form-36 Survey legacy instruments in clarity, translatability, patient importance, reliability, and sensitivity to change. Conclusion. Precise measures, such as PROMIS, efficiently incorporate patient self-report of health into research, potentially reducing research cost by lowering sample size requirements. The advent of routine IRT applications has the potential to transform PRO measurement. C1 [Fries, James F.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. NIAMSD, NIAMS, Bethesda, MD USA. [Rose, Matthias] Univ Med Berlin, Med Sch Charite, Berlin, Germany. Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. Univ Michigan, Sch Med, Dept Med, Ann Arbor, MI 48104 USA. [Morgan-DeWitt, Esi] Univ Cincinnati, Sch Med, Dept Pediat, Cincinnati, OH USA. RP Cella, D (reprint author), Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. EM d-cella@northwestern.edu RI Rose, Matthias/A-8920-2015; Fries, James/F-6271-2011 FU NIAMS FX Supported under the PROMIS-Initiative funded by NIAMS, with multiple grants to the listed institutions and others to support development of unproved patient-reported outcomes items, instruments, and applications. NR 15 TC 21 Z9 21 U1 0 U2 7 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2014 VL 41 IS 1 BP 153 EP 158 DI 10.3899/jrheum.130813 PG 6 WC Rheumatology SC Rheumatology GA AA5QF UT WOS:000331154000026 PM 24241485 ER PT J AU Daye, PM Blohm, G Lefevre, P AF Daye, Pierre M. Blohm, Gunnar Lefevre, Phillippe TI Catch-up saccades in head-unrestrained conditions reveal that saccade amplitude is corrected using an internal model of target movement SO JOURNAL OF VISION LA English DT Article DE gaze shifts; head-free; saccade-pursuit interactions ID PREDICTIVE SMOOTH-PURSUIT; COMPLEX 2-DIMENSIONAL TRAJECTORIES; MOVING VISUAL TARGET; EYE-MOVEMENTS; GAZE SHIFTS; QUANTITATIVE-ANALYSIS; OCULAR PURSUIT; SYSTEM; COORDINATION; RESPONSES AB This study analyzes how human participants combine saccadic and pursuit gaze movements when they track an oscillating target moving along a randomly oriented straight line with the head free to move. We found that to track the moving target appropriately, participants triggered more saccades with increasing target oscillation frequency to compensate for imperfect tracking gains. Our sinusoidal paradigm allowed us to show that saccade amplitude was better correlated with internal estimates of position and velocity error at saccade onset than with those parameters 100 ms before saccade onset as head-restrained studies have shown. An analysis of saccadic onset time revealed that most of the saccades were triggered when the target was accelerating. Finally, we found that most saccades were triggered when small position errors were combined with large velocity errors at saccade onset. This could explain why saccade amplitude was better correlated with velocity error than with position error. Therefore, our results indicate that the triggering mechanism of head-unrestrained catch-up saccades combines position and velocity error at saccade onset to program and correct saccade amplitude rather than using sensory information 100 ms before saccade onset. C1 [Daye, Pierre M.; Lefevre, Phillippe] Catholic Univ Louvain, ICTEAM Inst, B-1348 Louvain, Belgium. [Daye, Pierre M.; Lefevre, Phillippe] Catholic Univ Louvain, IoNS Inst Neursci, B-1200 Brussels, Belgium. [Daye, Pierre M.] NEI, NIH, Sensorimotor Res Lab, Bethesda, MD 20892 USA. [Blohm, Gunnar] Queens Univ, Ctr Neurosci Studies, Kingston, ON, Canada. RP Daye, PM (reprint author), NEI, NIH, Sensorimotor Res Lab, Bethesda, MD 20892 USA. EM pierre.daye@nih.gov FU Intramural Research Program of the National Eye Institute; National Science and Engineering Reserach Council (Canada); Ontario Research Fund (Canada); Canadian Foundation for Innovation (Canada); Botterell Foundation (Queens University, Kingston, ON, Canada); Fonds National de la Recherche Scientifique, Action de Recherche Concertee (Belgium); Interuniversity Attraction Poles Programmes; Belgian State, Science Policy Office FX Dr. Daye was supported by the Intramural Research Program of the National Eye Institute. Dr. Blohm has been supported by the National Science and Engineering Reserach Council (Canada), the Ontario Research Fund (Canada), the Canadian Foundation for Innovation (Canada), and the Botterell Foundation (Queens University, Kingston, ON, Canada). De. Lefevre has been supported by Fonds National de la Recherche Scientifique, Action de Recherche Concertee (Belgium). This paper presents research results of the Belgian Network Dynamical Systems, Control and Optimization, funded by the Interuniversity Attraction Poles Programmes, initiated by the Belgian State, Science Policy Office. NR 42 TC 3 Z9 3 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2014 VL 14 IS 1 AR 12 DI 10.1167/14.1.12 PG 18 WC Ophthalmology SC Ophthalmology GA AA6QN UT WOS:000331223000012 ER PT J AU Perrone, JA Krauzlis, RJ AF Perrone, John A. Krauzlis, Richard J. TI Simulating component-to-pattern dynamic effects with a computer model of middle temporal pattern neurons SO JOURNAL OF VISION LA English DT Article DE motion; motion models; middle temporal (MT); pattern motion; temporal effects; transparency ID VISUAL AREA MT; SPATIOTEMPORAL ENERGY MODELS; MOTION PERCEPTION; FREQUENCY-SELECTIVITY; TRANSPARENT MOTION; STRIATE CORTEX; MACAQUE MONKEY; SPEED; COHERENCE; DIRECTION AB Some primate motion-sensitive middle temporal (MT) neurons respond best to motion orthogonal to a contour's orientation (component types) whereas another class (pattern type) responds maximally to the overall pattern motion. We have previously developed a model of the pattern-type neurons using integration of the activity generated in speed-and direction-tuned subunits. However, a number of other models have also been able to replicate MT neuron pattern-like behavior using a diverse range of mechanisms. This basic property does not really challenge or help discriminate between the different model types. There exist two sets of findings that we believe provide a better yardstick against which to assess MT pattern models. Some MT neurons have been shown to change from component to pattern behavior over brief time intervals. MT neurons have also been observed to switch from component-to pattern-like behavior when the intensity of the intersections in a plaid pattern stimulus changes. These properties suggest more complex time-and contrast-sensitive internal mechanisms underlying pattern motion extraction, which provide a real challenge for modelers. We have now replicated these two component-to-pattern effects using our MT pattern model. It incorporates two types of V1 neurons (sustained and transient), and these have slightly different time delays; this initially favors the component response, thus mimicking the temporal effects. We also discovered that some plaid stimuli contain a contrast asymmetry that depends on the plaid direction and the intensity of the intersections. This causes the model MT pattern units to act as component units. C1 [Perrone, John A.] Univ Waikato, Sch Psychol, Hamilton, New Zealand. [Krauzlis, Richard J.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Perrone, JA (reprint author), Univ Waikato, Sch Psychol, Hamilton, New Zealand. EM jpnz@waikato.ac.nz FU Marsden Fund Council from Government FX Thanks to the two anonymous reviewers for their helpful comments. Supported by the Marsden Fund Council from Government funding, administered by the Royal Society of New Zealand. NR 54 TC 0 Z9 0 U1 1 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2014 VL 14 IS 1 AR 19 DI 10.1167/14.1.19 PG 17 WC Ophthalmology SC Ophthalmology GA AA6QN UT WOS:000331223000019 ER PT J AU Lin, YS Li, XY Willis, AL Liu, CY Chen, GK Weiss, SJ AF Lin, Yongshun Li, Xiao-Yan Willis, Amanda L. Liu, Chengyu Chen, Guokai Weiss, Stephen J. TI Snail1-dependent control of embryonic stem cell pluripotency and lineage commitment SO NATURE COMMUNICATIONS LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; GENE-EXPRESSION SIGNATURE; BREAST-CANCER; SELF-RENEWAL; MOUSE GASTRULATION; AXIS FORMATION; GROUND-STATE; BETA-CATENIN; WNT; EPIBLAST AB Embryonic stem cells (ESCs) exhibit the dual properties of self-renewal and pluripotency as well as the ability to undergo differentiation that gives rise to all three germ layers. Wnt family members can both promote ESC maintenance and trigger differentiation while also controlling the expression of Snail1, a zinc-finger transcriptional repressor. Snail1 has been linked to events ranging from cell cycle regulation and cell survival to epithelial-mesenchymal transition (EMT) and gastrulation, but its role in self-renewal, pluripotency or lineage commitment in ESCs remains undefined. Here we demonstrate using isogenic pairs of conditional knockout mouse ESCs, that Snail1 exerts Wnt- and EMT independent control over the stem cell transcriptome without affecting self-renewal or pluripotency-associated functions. By contrast, during ESC differentiation, an endogenous Wnt-mediated burst in Snail1 expression regulates neuroectodermal fate while playing a required role in epiblast stem cell exit and the consequent lineage fate decisions that define mesoderm commitment. C1 [Lin, Yongshun; Li, Xiao-Yan; Willis, Amanda L.; Weiss, Stephen J.] Univ Michigan, Inst Life Sci, Dept Internal Med, Div Mol Med & Genet, Ann Arbor, MI 48109 USA. [Lin, Yongshun; Liu, Chengyu; Chen, Guokai] NHLBI, Ctr Mol Med, Bethesda, MD 20892 USA. RP Weiss, SJ (reprint author), Univ Michigan, Inst Life Sci, Dept Internal Med, Div Mol Med & Genet, Ann Arbor, MI 48109 USA. EM sjweiss@umich.edu FU Breast Cancer Research Foundation; MDRTC Cell and Molecular Biology Core NIH Grant [P60 DK020572] FX This work was supported by the Breast Cancer Research Foundation (S.J.W). Work performed in this study was also supported by MDRTC Cell and Molecular Biology Core NIH Grant P60 DK020572. NR 71 TC 19 Z9 20 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JAN PY 2014 VL 5 AR 3070 DI 10.1038/ncomms4070 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AA4RQ UT WOS:000331084200012 PM 24401905 ER PT J AU Barbosa, IG Machado-Vieira, R Soares, JC Teixeira, AL AF Barbosa, Izabela Guimaraes Machado-Vieira, Rodrigo Soares, Jair C. Teixeira, Antonio L. TI The Immunology of Bipolar Disorder SO NEUROIMMUNOMODULATION LA English DT Article DE Mania; Depression; Aspirin; Interleukin; Lymphocytes; Mood disorder ID AUTOIMMUNE-THYROIDITIS; LITHIUM TREATMENT; OXIDATIVE STRESS; MOOD DISORDERS; IMMUNE-SYSTEM; ACUTE MANIA; T-CELLS; CYTOKINES; SCHIZOPHRENIA; INFLAMMATION AB Bipolar disorder (BD) is a psychiatric condition associated with elevated frequency of clinical comorbidities and cognitive impairment. The neurobiology of BD is not completely understood. Recent evidence has implicated immune dysfunction in its physiopathology. Here, we review several data supporting the presence of immunological dysfunction in BD: (i) increased frequency of autoimmune diseases; (ii) distinct immune cell profile; (iii) release of/altered cytokines by stimulated mononuclear cells; (iv) elevated levels of circulating immune markers, and (v) inflammatory changes in the central nervous system. We also discuss the interplay between immunological dysfunction and neuroprogression in BD. (C) 2014 S. Karger AG, Basel C1 [Barbosa, Izabela Guimaraes; Teixeira, Antonio L.] Univ Fed Minas Gerais, Lab Interdisciplinar Invest Med, Fac Med, BR-30130100 Belo Horizonte, MG, Brazil. [Teixeira, Antonio L.] Univ Fed Minas Gerais, IEAT, BR-30130100 Belo Horizonte, MG, Brazil. [Machado-Vieira, Rodrigo] Univ Sao Paulo, Inst & Dept Psiquiatria, Lab Neurociencias, LIM27, Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. [Soares, Jair C.] UTHlth Med Sch, Dept Psychiat & Behav Sci, Houston, TX USA. RP Barbosa, IG (reprint author), Univ Fed Minas Gerais, Lab Interdisciplinar Invest Med, Fac Med, Av Prof Alfredo Balena 190,Room 281, BR-30130100 Belo Horizonte, MG, Brazil. EM izabelagb@gmail.com RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU CNPq; Fapemig, Brazil; Stanley Medical Research Institute; CAPES scholarship FX This work was partly funded by CNPq and Fapemig, Brazil. Jair C. Soares was partly supported by the Pat R. Rutherford Jr. Chair in Psychiatry, Department of Psychiatry and Behavioral Sciences, UTHealth Medical School, and also by the Stanley Medical Research Institute. Dr. Barbosa is recipient of a CAPES scholarship. Dr. Machado-Vieira would like to thank Sao Paulo Research Foundation, Brazil and National Institute of Mental Health, USA. NR 45 TC 32 Z9 35 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 EI 1423-0216 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2014 VL 21 IS 2-3 BP 117 EP 122 DI 10.1159/000356539 PG 6 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA AB0NA UT WOS:000331488100008 PM 24557044 ER PT J AU Devan, BD Pistell, PJ Duffy, KB Kelley-Bell, B Spangler, EL Ingram, DK AF Devan, Bryan D. Pistell, Paul J. Duffy, Kara B. Kelley-Bell, Bennett Spangler, Edward L. Ingram, Donald K. TI Phosphodiesterase inhibition facilitates cognitive restoration in rodent models of age-related memory decline SO NEUROREHABILITATION LA English DT Article DE Alzheimer's disease; animal models; phosphodiesterase inhibition; cognitive enhancement ID LONG-TERM POTENTIATION; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; RECEPTOR ANTAGONIST MEMANTINE; MORRIS WATER MAZE; ALZHEIMERS-DISEASE; NITRIC-OXIDE; TREATMENT STRATEGIES; ACETYLCHOLINESTERASE INHIBITOR; CHOLINERGIC HYPOTHESIS; LEARNING IMPAIRMENT AB BACKGROUND: Previous studies have shown that cyclic nucleotide phosphodiesterase type 5 (PDE5) inhibition with the drugs sildenafil and vardenafil can enhance spatial performance and object recognition in rodent models of learning and memory. OBJECTIVE: We review recent studies on PDE5 inhibition and report novel data that specifically tests the systemic effects of both pharmacological agents in aged rats using two different spatial learning/memory paradigms. METHODS: The 14-unit T-maze was used as a test of egocentric spatial processing that requires rats to learn a series of left/right turns to avoid mild footshock. The Morris water maze is a test of allocentric spatial learning that requires the acquisition of place information to localize a hidden platform relative to distal room cues. RESULTS: In both cases, acquisition (i.e., learning performance) was not improved, however after a one week drug washout period, aged animals demonstrated improved spatial memory retention compared to aged controls, ruling out simple performance effects. CONCLUSIONS: These findings are discussed in relation to recent reports on the use of PDE inhibitors to treat Alzheimer's disease (AD) dementia and age-related memory impairments. While some report promising pre-clinical results, others note that PDE5 may not be an appropriate target in AD due to a lack of localization within critical brain structures where therapeutic activity is needed. Despite these limitations, PDE5 inhibition may produce beneficial effects via several mechanisms that target predisposing risk factors leading to increased incidence of memory impairment in aged individuals and influence memory consolidation mechanisms that preserve long-term retention of cognitive information. C1 [Devan, Bryan D.; Pistell, Paul J.; Kelley-Bell, Bennett] Towson Univ, Dept Psychol, Lab Comparat Neuropsychol, Towson, MD 21252 USA. [Devan, Bryan D.; Pistell, Paul J.; Duffy, Kara B.; Spangler, Edward L.; Ingram, Donald K.] NIA, Behav Neurosci Sect, Lab Expt Gerontol, NIH,Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Devan, BD (reprint author), Towson Univ, Dept Psychol, 8000 York Rd, Towson, MD 21252 USA. EM bdevan@towson.edu NR 88 TC 6 Z9 6 U1 0 U2 10 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 EI 1878-6448 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2014 VL 34 IS 1 BP 101 EP 111 DI 10.3233/NRE-131022 PG 11 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AA4JN UT WOS:000331062000012 PM 24284467 ER PT B AU Bell, AH Pasternak, T Ungerleider, LG AF Bell, Andrew H. Pasternak, Tatiana Ungerleider, Leslie G. BE Werner, JS Chalupa, LM TI Ventral and Dorsal Cortical Processing Streams SO NEW VISUAL NEUROSCIENCES LA English DT Article; Book Chapter ID TEMPORAL VISUAL AREA; MONKEY INFEROTEMPORAL CORTEX; LATERAL INTRAPARIETAL AREA; HUMAN EXTRASTRIATE CORTEX; INVARIANT OBJECT REPRESENTATION; PERCEPTION FOLLOWING LESIONS; LONG-TERM-MEMORY; WORD FORM AREA; PARIETAL CORTEX; MACAQUE MONKEY C1 [Bell, Andrew H.] Univ Cambridge, MRC, Cognit & Brain Sci Unit, Cambridge, England. [Pasternak, Tatiana] Univ Rochester, Dept Neurobiol & Anat, Rochester, NY USA. [Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Bell, AH (reprint author), Univ Cambridge, MRC, Cognit & Brain Sci Unit, Cambridge, England. NR 106 TC 1 Z9 1 U1 2 U2 4 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-01916-3; 978-0-262-31789-4 PY 2014 BP 227 EP 242 PG 16 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA BJS84 UT WOS:000330033700018 ER PT B AU Krauzlis, RJ AF Krauzlis, Richard J. BE Werner, JS Chalupa, LM TI Superior Colliculus and Visual Attention SO NEW VISUAL NEUROSCIENCES LA English DT Article; Book Chapter ID SACCADIC EYE-MOVEMENTS; COMPETITIVE STIMULUS SELECTION; RECEPTIVE-FIELD ORGANIZATION; COLLISION-SENSITIVE NEURONS; RETINAL GANGLION-CELLS; CHICKS GALLUS-GALLUS; OWL OPTIC TECTUM; CORTICAL AREA MT; TARGET SELECTION; SUBSTANTIA-NIGRA C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Krauzlis, RJ (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 112 TC 0 Z9 0 U1 1 U2 4 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-01916-3; 978-0-262-31789-4 PY 2014 BP 323 EP 337 PG 15 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA BJS84 UT WOS:000330033700024 ER PT B AU Optican, LM Daye, PM Quaia, C AF Optican, Lance M. Daye, Pierre M. Quaia, Christian BE Werner, JS Chalupa, LM TI Neural Mechanisms of Fixations and Saccades: The Eye Plant and Low-Level Control SO NEW VISUAL NEUROSCIENCES LA English DT Article; Book Chapter ID MONKEY SUPERIOR COLLICULUS; PONTINE OMNIPAUSE NEURONS; DIRECT INHIBITORY PROJECTION; FASTIGIAL OCULOMOTOR REGION; RETICULAR-FORMATION NEURONS; TO-POSITION TRANSFORMATION; VISUALLY GUIDED SACCADES; LEAD BURST NEURONS; FOREL FIELD-H; CEREBELLAR VERMIS C1 [Optican, Lance M.; Daye, Pierre M.; Quaia, Christian] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Optican, LM (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 119 TC 0 Z9 0 U1 2 U2 5 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-01916-3; 978-0-262-31789-4 PY 2014 BP 865 EP 877 PG 13 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA BJS84 UT WOS:000330033700061 ER PT B AU Sommer, MA Wurtz, RH AF Sommer, Marc A. Wurtz, Robert H. BE Werner, JS Chalupa, LM TI The Dialogue between Cerebral Cortex and Superior Colliculus: Multiple Ascending Pathways for Corollary Discharge SO NEW VISUAL NEUROSCIENCES LA English DT Article; Book Chapter ID FRONTAL EYE FIELD; BRAIN-STEM TELLS; SACCADIC SUPPRESSION; RECEPTIVE FIELDS; VISUAL-STABILITY; MONKEY; MOVEMENTS; NEURONS; RESPONSES; PULVINAR C1 [Sommer, Marc A.] Duke Univ, Dept Biomed Engn, Ctr Cognit Neurosci, Durham, NC 27706 USA. [Sommer, Marc A.] Duke Univ, Duke Inst Brain Sci, Durham, NC USA. [Wurtz, Robert H.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Sommer, MA (reprint author), Duke Univ, Dept Biomed Engn, Ctr Cognit Neurosci, Durham, NC 27706 USA. NR 45 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-01916-3; 978-0-262-31789-4 PY 2014 BP 935 EP 945 PG 11 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA BJS84 UT WOS:000330033700066 ER PT J AU Kozlenkov, A Roussos, P Timashpolsky, A Barbu, M Rudchenko, S Bibikova, M Klotzle, B Byne, W Lyddon, R Di Narzo, AF Hurd, YL Koonin, EV Dracheva, S AF Kozlenkov, Alexey Roussos, Panos Timashpolsky, Alisa Barbu, Mihaela Rudchenko, Sergei Bibikova, Marina Klotzle, Brandy Byne, William Lyddon, Rebecca Di Narzo, Antonio Fabio Hurd, Yasmin L. Koonin, Eugene V. Dracheva, Stella TI Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BODY-SPECIFIC METHYLATION; GENOME BROWSER DATABASE; HUMAN PREFRONTAL CORTEX; CENTRAL-NERVOUS-SYSTEM; HUMAN BRAIN; GENE-EXPRESSION; EPIGENETIC MECHANISMS; HISTONE MODIFICATIONS; MAMMALIAN DEVELOPMENT; NETWORK ANALYSIS AB We applied Illumina Human Methylation450K array to perform a genomic-scale single-site resolution DNA methylation analysis in neuronal and nonneuronal (primarily glial) nuclei separated from the orbitofrontal cortex of postmortem human brain. The findings were validated using enhanced reduced representation bisulfite sequencing. We identified thousands of sites differentially methylated (DM) between neuronal and nonneuronal cells. The DM sites were depleted within CpG-island-containing promoters but enriched in predicted enhancers. Classification of the DM sites into those undermethylated in neurons (neuronal type) and those undermethylated in nonneuronal cells (glial type), combined with findings of others that methylation within control elements typically negatively correlates with gene expression, yielded large sets of predicted neuron-specific and nonneuron-specific genes. These sets of predicted genes were in excellent agreement with the available direct measurements of gene expression in human and mouse. We also found a distinct set of DNA methylation patterns that were unique for neuronal cells. In particular, neuronal-type differential methylation was overrepresented in CpG island shores, enriched within gene bodies but not in intergenic regions, and preferentially harbored binding motifs for a distinct set of transcription factors, including neuron-specific activity-dependent factors. Finally, non-CpG methylation was substantially more prevalent in neurons than in nonneuronal cells. C1 [Kozlenkov, Alexey; Roussos, Panos; Timashpolsky, Alisa; Byne, William; Lyddon, Rebecca; Dracheva, Stella] James J Peters VA Med Ctr, Educ & Clin Ctr MIRECC, VISN Mental Illness Res 3, Bronx, NY 10468 USA. [Kozlenkov, Alexey; Roussos, Panos; Byne, William; Lyddon, Rebecca; Hurd, Yasmin L.; Dracheva, Stella] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY USA. [Kozlenkov, Alexey; Roussos, Panos; Byne, William; Lyddon, Rebecca; Hurd, Yasmin L.; Dracheva, Stella] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA. [Roussos, Panos; Di Narzo, Antonio Fabio] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY USA. [Barbu, Mihaela; Rudchenko, Sergei] Hosp Special Surg, Div Res, New York, NY 10021 USA. [Bibikova, Marina; Klotzle, Brandy] Illumina Inc, San Diego, CA USA. [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Dracheva, S (reprint author), James J Peters VA Med Ctr, Educ & Clin Ctr MIRECC, VISN Mental Illness Res 3, Bronx, NY 10468 USA. EM Stella.Dracheva@mssm.edu RI Roussos, Panos/J-7090-2013 OI Roussos, Panos/0000-0002-4640-6239 FU National Institute on Drug Abuse [R21DA031557]; National Institute of Mental Health [R21MH090352]; Hope for Depression Research Foundation; VISN 3 Mental Illness Research, Education and Clinical Center (MIRECC); US Department of Health and Human Services FX National Institute on Drug Abuse [R21DA031557 to S. D.]; National Institute of Mental Health [R21MH090352 to S. D.]; Hope for Depression Research Foundation grants (to S. D.); VISN 3 Mental Illness Research, Education and Clinical Center (MIRECC) (to S. D.). The work was also supported with resources and the use of facilities at the James J Peters VA Medical Center, Bronx, NY; Supported by intramural funds of the US Department of Health and Human Services (to National Library of Medicine) (to E. V. K.). Funding for open access charge: Authors' funding. NR 107 TC 41 Z9 41 U1 3 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS 1 BP 109 EP 127 DI 10.1093/nar/gkt838 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5KF UT WOS:000331136000016 PM 24057217 ER PT J AU Sui, HY Zhou, M Chen, Q Lane, HC Imamichi, T AF Sui, Hongyan Zhou, Ming Chen, Qian Lane, H. Clifford Imamichi, Tomozumi TI siRNA enhances DNA-mediated interferon lambda-1 response through crosstalk between RIG-I and IFI16 signalling pathway SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DOUBLE-STRANDED-RNA; INNATE IMMUNE-RESPONSE; TOLL-LIKE RECEPTOR-3; FAS PROTECTS MICE; NF-KAPPA-B; INTRACELLULAR DNA; STRUCTURAL BASIS; MAMMALIAN-CELLS; RECOGNITION; ACTIVATION AB In addition to silencing specific genes, small interfering RNA (siRNA) transfection is also associated with the non-specific induction of inflammatory cytokines and type I interferon. Those so-called "off-target" effects have considerable implications for the interpretation of in vitro studies and clinical application of siRNA. The present study attempted to develop a better understanding of the mechanism involved in these off target effects. Synthesized siRNA significantly enhances DNA-mediated interferon lambda-1 response (IFN-lambda 1/IL-29), a newly characterized antiviral interferon in non-immune or primary immune cells. This enhancement was most pronounced by double-stranded siRNA with at least a 2-nucleotide overhang at one 3' terminus in a dose-dependent manner, while the presence of DNA was indispensable. A pull-down assay using biotinylated siRNA- or DNA-conjugated beads indicated that retinoic acid-inducible gene I (RIG-I) and interferon gamma-inducible protein 16 (IFI16) were involved in the sensing of siRNA and DNA, respectively. Co-immunoprecipitation analysis further revealed that RIG-I and IFI16 formed a complex via siRNA, and the dissociation of IFI16 from this complex in the presence of DNA activated the downstream STING-TBK1-IRF3 (stimulator of interferon genes - tank-binding kinase 1 - interferon regulatory factor 3) pathway, shedding light on a new physiological signalling pathway to activate innate immunity. Collectively, these findings may provide rational information for siRNA-induced innate immunity, with important implications for developing siRNA-based reagents to control human diseases. C1 [Sui, Hongyan; Chen, Qian; Imamichi, Tomozumi] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Appl & Dev Directorate, Lab Human Retrovirol,Clin Serv Program, Frederick, MD 21702 USA. [Zhou, Ming] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD 21702 USA. [Lane, H. Clifford] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Imamichi, T (reprint author), SAIC Frederick Inc, Frederick Natl Lab Canc Res, Appl & Dev Directorate, Lab Human Retrovirol,Clin Serv Program, Frederick, MD 21702 USA. EM timamichi@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX Federal funds from the National Cancer Institute, National Institutes of Health [contract No. HHSN261200800001E] (whole or in part). The content of this publication does not necessarily reflect the reviews 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. Finding for open access: Federal funds from the National Cancer Institute, National Institutes of Health [contract No. HHSN261200800001E] (whole or in part). NR 47 TC 8 Z9 9 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS 1 BP 583 EP 598 DI 10.1093/nar/gkt844 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5KF UT WOS:000331136000052 PM 24049081 ER PT J AU Kong, KYE Tang, HMV Pan, KW Huang, Z Lee, THJ Hinnebusch, AG Jin, DY Wong, CM AF Kong, Ka-Yiu Edwin Tang, Hei-Man Vincent Pan, Kewu Huang, Zhe Lee, Tsz-Hang Jimmy Hinnebusch, Alan G. Jin, Dong-Yan Wong, Chi-Ming TI Cotranscriptional recruitment of yeast TRAMP complex to intronic sequences promotes optimal pre-mRNA splicing SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CAP-BINDING COMPLEX; IN-VIVO COMMITMENT; SACCHAROMYCES-CEREVISIAE; NUCLEAR EXOSOME; TRANSCRIPTION ELONGATION; QUALITY-CONTROL; POLY(A) POLYMERASE; BIDIRECTIONAL PROMOTERS; DEGRADATION PATHWAY; CONTAINING GENES AB Most unwanted RNA transcripts in the nucleus of eukaryotic cells, such as splicing-defective pre-mRNAs and spliced-out introns, are rapidly degraded by the nuclear exosome. In budding yeast, a number of these unwanted RNA transcripts, including spliced-out introns, are first recognized by the nuclear exosome cofactor Trf4/5p-Air1/2p-Mtr4p polyadenylation (TRAMP) complex before subsequent nuclear-exosome-mediated degradation. However, it remains unclear when splicedout introns are recognized by TRAMP, and whether TRAMP may have any potential roles in pre-mRNA splicing. Here, we demonstrated that TRAMP is cotranscriptionally recruited to nascent RNA transcripts, with particular enrichment at intronic sequences. Deletion of TRAMP components led to further accumulation of unspliced pre-mRNAs even in a yeast strain defective in nuclear exosome activity, suggesting a novel stimulatory role of TRAMP in splicing. We also uncovered new genetic and physical interactions between TRAMP and several splicing factors, and further showed that TRAMP is required for optimal recruitment of the splicing factor Msl5p. Our study provided the first evidence that TRAMP facilitates pre-mRNA splicing, and we interpreted this as a fail-safe mechanism to ensure the cotranscriptional recruitment of TRAMP before or during splicing to prepare for the subsequent targeting of spliced-out introns to rapid degradation by the nuclear exosome. C1 [Kong, Ka-Yiu Edwin; Tang, Hei-Man Vincent; Jin, Dong-Yan] Univ Hong Kong, Li Ka Shing Fac Med, Dept Biochem, Pokfulam, Hong Kong, Peoples R China. [Pan, Kewu; Huang, Zhe; Lee, Tsz-Hang Jimmy; Wong, Chi-Ming] Univ Hong Kong, Li Ka Shing Fac Med, Dept Med, Pokfulam, Hong Kong, Peoples R China. [Pan, Kewu; Huang, Zhe; Lee, Tsz-Hang Jimmy; Wong, Chi-Ming] Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Li Ka Shing Fac Med, Pokfulam, Hong Kong, Peoples R China. [Hinnebusch, Alan G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Wong, CM (reprint author), Univ Hong Kong, Li Ka Shing Fac Med, Dept Med, 21 Sassoon Rd, Pokfulam, Hong Kong, Peoples R China. EM dyjin@hku.hk; wispwong@hku.hk OI Wong, Chi-Ming/0000-0002-0025-7135 FU National Institutes of Health (NIH) [1R01TW00 829801A1, 1R01TW00829801]; National Natural Science Foundation of China [31271361]; Intramural Program of the National Institutes of Health FX National Institutes of Health (NIH) [1R01TW00 829801A1 to C. M. W.]; National Natural Science Foundation of China [31271361 to C. M. W.]; this research was supported in part by the Intramural Program of the National Institutes of Health. Funding for open access charge: NIH [1R01TW00829801]; National Natural Science Foundation of China [31271361]. NR 77 TC 8 Z9 8 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS 1 BP 643 EP 660 DI 10.1093/nar/gkt888 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5KF UT WOS:000331136000057 PM 24097436 ER PT J AU Cui, F Zhurkin, VB AF Cui, Feng Zhurkin, Victor B. TI Rotational positioning of nucleosomes facilitates selective binding of p53 to response elements associated with cell cycle arrest SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSCRIPTION-FACTOR-BINDING; CRYSTAL-STRUCTURE; DNA-SEQUENCE; GENE-REGULATION; CORE PARTICLE; HUMAN GENOME; APOPTOSIS; SITES; RECRUITMENT; ACTIVATION AB The tumor suppressor protein p53 exhibits high affinity to the response elements regulating cell cycle arrest genes (CCA-sites), but relatively low affinity to the sites associated with apoptosis (Apo-sites). This in vivo tendency cannot be explained solely by the p53-DNA binding constants measured in vitro. Since p53 can bind nucleosomal DNA, we sought to understand if the two groups of p53 sites differ in their accessibility when embedded in nucleosomes. To this aim, we analyzed the sequence-dependent bending anisotropy of human genomic DNA containing p53 sites. For the 20 CCA-sites, we calculated rotational positioning patterns predicting that most of the sites are exposed on the nucleosomal surface. This is consistent with experimentally observed positioning of human nucleosomes. Remarkably, the sequence-dependent DNA anisotropy of both the p53 sites and flanking DNA work in concert producing strong positioning signals. By contrast, both the predicted and observed rotational settings of the 38 Apo-sites in nucleosomes suggest that many of these sites are buried inside, thus preventing immediate p53 recognition and delaying gene induction. The distinct chromatin organization of the CCA response elements appears to be one of the key factors facilitating p53-DNA binding and subsequent activation of genes associated with cell cycle arrest. C1 [Cui, Feng] Rochester Inst Technol, Thomas H Gosnell Sch Life Sci, Rochester, NY 14623 USA. [Zhurkin, Victor B.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zhurkin, VB (reprint author), NCI, Cell Biol Lab, NIH, Bg 37,Room 3035A,Convent Dr, Bethesda, MD 20892 USA. EM zhurkin@nih.gov FU National Institutes of Health (Center for Cancer Research, National Cancer Institute); Rochester Institute of Technology; NIH Intramural Program FX The Intramural Research Program of the National Institutes of Health (Center for Cancer Research, National Cancer Institute) and Grant Writers' Boot Camp Seed Funding Program of the Rochester Institute of Technology. Funding for open access charge: NIH Intramural Program. NR 74 TC 8 Z9 9 U1 3 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS 2 BP 836 EP 847 DI 10.1093/nar/gkt943 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5KS UT WOS:000331138100019 PM 24153113 ER PT J AU Henderson, A Wu, YL Huang, YC Chavez, EA Platt, J Johnson, FB Brosh, RM Sen, D Lansdorp, PM AF Henderson, Alexander Wu, Yuliang Huang, Yu Chuan Chavez, Elizabeth A. Platt, Jesse Johnson, F. Brad Brosh, Robert M., Jr. Sen, Dipankar Lansdorp, Peter M. TI Detection of G-quadruplex DNA in mammalian cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID OXYTRICHA TELOMERIC DNA; G-QUARTET; SACCHAROMYCES-CEREVISIAE; GENOMIC STABILITY; CRYSTAL-STRUCTURE; BINDING PROTEINS; NUCLEIC-ACIDS; COMPLEXES; SEQUENCE; ANTIBODY AB It has been proposed that guanine-rich DNA forms four-stranded structures in vivo called G-quadruplexes or G4 DNA. G4 DNA has been implicated in several biological processes, but tools to study G4 DNA structures in cells are limited. Here we report the development of novel murine monoclonal antibodies specific for different G4 DNA structures. We show that one of these antibodies designated 1H6 exhibits strong nuclear staining in most human and murine cells. Staining intensity increased on treatment of cells with agents that stabilize G4 DNA and, strikingly, cells deficient in FANCJ, a G4 DNA-specific helicase, showed stronger nuclear staining than controls. Our data strongly support the existence of G4 DNA structures in mammalian cells and indicate that the abundance of such structures is increased in the absence of FANCJ. We conclude that monoclonal antibody 1H6 is a valuable tool for further studies on the role of G4 DNA in cell and molecular biology. C1 [Henderson, Alexander; Chavez, Elizabeth A.; Lansdorp, Peter M.] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. [Wu, Yuliang; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, Baltimore, MD 21224 USA. [Huang, Yu Chuan; Sen, Dipankar] Simon Fraser Univ, Dept Chem, Burnaby, BC V5A 1S6, Canada. [Platt, Jesse; Johnson, F. Brad] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Lansdorp, Peter M.] Univ British Columbia, Div Hematol, Dept Med, Vancouver, BC V6T 1Z4, Canada. [Lansdorp, Peter M.] Univ Groningen, Univ Med Ctr Groningen, European Res Inst Biol Ageing, NL-9713 AV Groningen, Netherlands. RP Lansdorp, PM (reprint author), British Columbia Canc Agcy, Terry Fox Lab, 601 W 10th Ave, Vancouver, BC V5Z 1L3, Canada. EM p.m.lansdorp@umcg.nl FU Canadian Institute of Health Research [MOP38075, GMH79042]; Terry Fox Foundation [018006]; National Institute of Health [GMH79042]; NIH, National Institute on Aging; ERC; BC Cancer Foundation FX We acknowledge support from the Canadian Institute of Health Research [MOP38075 and GMH79042 to P. L.] and the Terry Fox Foundation (Program Project Award 018006), the National Institute of Health [GMH79042] and by the Intramural Research program of the NIH, National Institute on Aging; An ERC Advanced grant (to P. L.). Funding for open access charge: BC Cancer Foundation. NR 59 TC 106 Z9 113 U1 11 U2 61 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS 2 BP 860 EP 869 DI 10.1093/nar/gkt957 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5KS UT WOS:000331138100021 PM 24163102 ER PT J AU Zhao, WX Saro, D Hammel, M Kwon, Y Xu, YY Rambo, RP Williams, GJ Chi, P Lu, L Pezza, RJ Camerini-Otero, RD Tainer, JA Wang, HW Sung, P AF Zhao, Weixing Saro, Dorina Hammel, Michal Kwon, YoungHo Xu, Yuanyuan Rambo, Robert P. Williams, Gareth J. Chi, Peter Lu, Lucy Pezza, Roberto J. Camerini-Otero, R. Daniel Tainer, John A. Wang, Hong-Wei Sung, Patrick TI Mechanistic insights into the role of Hop2-Mnd1 in meiotic homologous DNA pairing SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DOUBLE-STRAND BREAK; RAD51 RECOMBINASE; GENETIC-RECOMBINATION; ARABIDOPSIS-THALIANA; SCATTERING SAXS; HOP2 PROTEIN; MEIOSIS; COMPLEX; DMC1; MND1 AB The Hop2-Mnd1 complex functions with the DMC1 recombinase in meiotic recombination. Hop2-Mnd1 stabilizes the DMC1-single-stranded DNA (ssDNA) filament and promotes the capture of the double-stranded DNA partner by the recombinase filament to assemble the synaptic complex. Herein, we define the action mechanism of Hop2-Mnd1 in DMC1-mediated recombination. Small angle X-ray scattering analysis and electron microscopy reveal that the heterodimeric Hop2-Mnd1 is a V-shaped molecule. We show that the protein complex harbors three distinct DNA binding sites, and determine their functional relevance. Specifically, the N-terminal double-stranded DNA binding functions of Hop2 and Mnd1 co-operate to mediate synaptic complex assembly, whereas ssDNA binding by the Hop2 C-terminus helps stabilize the DMC1-ssDNA filament. A model of the Hop2-Mnd1-DMC1-ssDNA ensemble is proposed to explain how it mediates homologous DNA pairing in meiotic recombination. C1 [Zhao, Weixing; Saro, Dorina; Kwon, YoungHo; Xu, Yuanyuan; Wang, Hong-Wei; Sung, Patrick] Yale Univ, Dept Mol Biophys & Biochem, Sch Med, New Haven, CT 06520 USA. [Hammel, Michal; Rambo, Robert P.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA. [Williams, Gareth J.; Tainer, John A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA. [Chi, Peter] Natl Taiwan Univ, Inst Biochem Sci, Taipei 10617, Taiwan. [Pezza, Roberto J.] Oklahoma Med Res Fdn, Cell Cycle & Canc Biol Program, Oklahoma City, OK 73104 USA. [Camerini-Otero, R. Daniel] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. [Wang, Hong-Wei] Tsinghua Univ, Sch Life Sci, Tsinghua Peking Joint Ctr Life Sci, Minist Educ,Key Lab Prot Sci,Ctr Struct Biol, Beijing 100084, Peoples R China. RP Sung, P (reprint author), Yale Univ, Dept Mol Biophys & Biochem, Sch Med, POB 6666, New Haven, CT 06520 USA. EM patrick.sung@yale.edu RI zhao, weixing/H-3154-2013; OI CHI, HUNG-YUAN/0000-0001-9229-8729 FU US National Institutes of Health [RO1ES015252, RO1CA168635, RO1ES007061, PO1CA092584]; National Science Council of Taiwan [NSC 99-2311-B-002-012, NSC 100-2311-B-002-009]; National Basic Research Program of China [2010CB912401]; National Center for Protein Sciences Beijing FX US National Institutes of Health [RO1ES015252, RO1CA168635, RO1ES007061 and PO1CA092584]; the National Science Council of Taiwan [NSC 99-2311-B-002-012 and NSC 100-2311-B-002-009]; and also by the National Basic Research Program of China [2010CB912401] and the National Center for Protein Sciences Beijing. Funding for open access charge: [RO1ES015252, RO1CA168635, RO1ES007061 and PO1CA092584]. NR 47 TC 15 Z9 15 U1 3 U2 24 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS 2 BP 906 EP 917 DI 10.1093/nar/gkt924 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5KS UT WOS:000331138100025 PM 24150939 ER PT J AU Mitra, M Hercik, K Byeon, IJL Ahn, J Hill, S Hinchee-Rodriguez, K Singer, D Byeon, CH Charlton, LM Nam, G Heidecker, G Gronenborn, AM Levin, JG AF Mitra, Mithun Hercik, Kamil Byeon, In-Ja L. Ahn, Jinwoo Hill, Shawn Hinchee-Rodriguez, Kathyrn Singer, Dustin Byeon, Chang-Hyeock Charlton, Lisa M. Nam, Gabriel Heidecker, Gisela Gronenborn, Angela M. Levin, Judith G. TI Structural determinants of human APOBEC3A enzymatic and nucleic acid binding properties SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HIV-1 NUCLEOCAPSID PROTEIN; SINGLE-STRANDED-DNA; INHIBIT LINE-1 RETROTRANSPOSITION; RNA-EDITING PROTEIN; CYTIDINE DEAMINASES; REVERSE TRANSCRIPTION; CRYSTAL-STRUCTURE; CATALYTIC DOMAIN; HUMAN CANCERS; VIRUS TYPE-1 AB Human APOBEC3A (A3A) is a single-domain cytidine deaminase that converts deoxycytidine residues to deoxyuridine in single-stranded DNA (ssDNA). It inhibits a wide range of viruses and endogenous retroelements such as LINE-1, but it can also edit genomic DNA, which may play a role in carcinogenesis. Here, we extend our recent findings on the NMR structure of A3A and report structural, biochemical and cell-based mutagenesis studies to further characterize A3A's deaminase and nucleic acid binding activities. We find that A3A binds ssRNA, but the RNA and DNA binding interfaces differ and no deamination of ssRNA is detected. Surprisingly, with only one exception (G105A), alanine substitution mutants with changes in residues affected by specific ssDNA binding retain deaminase activity. Furthermore, A3A binds and deaminates ssDNA in a length-dependent manner. Using catalytically active and inactive A3A mutants, we show that the determinants of A3A deaminase activity and anti-LINE-1 activity are not the same. Finally, we demonstrate A3A's potential to mutate genomic DNA during transient strand separation and show that this process could be counteracted by ssDNA binding proteins. Taken together, our studies provide new insights into the molecular properties of A3A and its role in multiple cellular and antiviral functions. C1 [Mitra, Mithun; Hercik, Kamil; Hinchee-Rodriguez, Kathyrn; Singer, Dustin; Nam, Gabriel; Levin, Judith G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Viral Gene Regulat, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. [Byeon, In-Ja L.; Ahn, Jinwoo; Byeon, Chang-Hyeock; Charlton, Lisa M.; Gronenborn, Angela M.] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15261 USA. [Byeon, In-Ja L.; Ahn, Jinwoo; Byeon, Chang-Hyeock; Charlton, Lisa M.; Gronenborn, Angela M.] Univ Pittsburgh, Sch Med, Pittsburgh Ctr HIV Prot Interact, Pittsburgh, PA 15261 USA. [Heidecker, Gisela] NCI, Frederick Natl Lab Canc Res, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Levin, JG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Viral Gene Regulat, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. EM amg100@pitt.edu; levinju@mail.nih.gov RI Mitra, Mithun/A-2133-2015 FU Intramural Research Program at the National Institutes of Health [Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Cancer Institute, HIV Drug Resistance Program; Center for Cancer Research; National Institutes of Health [P50GM082251]; NIH/NICHD FX Intramural Research Program at the National Institutes of Health [Eunice Kennedy Shriver National Institute of Child Health and Human Development ( to M. M., K. H., K. H-R., D. S., G.N. and J.G.L.) and the National Cancer Institute, HIV Drug Resistance Program and Center for Cancer Research (to S. H. and G. H.)]; and the National Institutes of Health [Grant P50GM082251 to J.A., I-L. B., C-H. B., L. M. C. and A. M. G.]. Funding for open access charge: Intramural Program of NIH/NICHD. NR 103 TC 22 Z9 22 U1 0 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS 2 BP 1095 EP 1110 DI 10.1093/nar/gkt945 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5KS UT WOS:000331138100039 PM 24163103 ER PT J AU Yoon, JH Abdelmohsen, K Srikantan, S Guo, R Yang, XL Martindale, JL Gorospe, M AF Yoon, Je-Hyun Abdelmohsen, Kotb Srikantan, Subramanya Guo, Rong Yang, Xiaoling Martindale, Jennifer L. Gorospe, Myriam TI Tyrosine phosphorylation of HuR by JAK3 triggers dissociation and degradation of HuR target mRNAs SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BINDING PROTEIN HUR; GENE-EXPRESSION; NUCLEAR IMPORT; STRESS; COMPLEXES; GRANULES; DECAY; TRANSLATION; STABILITY; PATHWAYS AB In response to stress conditions, many mammalian mRNAs accumulate in stress granules (SGs) together with numerous RNA-binding proteins that control mRNA turnover and translation. However, the signaling cascades that modulate the presence of ribonucleoprotein (RNP) complexes in SGs are poorly understood. Here, we investigated the localization of human antigen R (HuR), an mRNA-stabilizing RNA-binding protein, in SGs following exposure to the stress agent arsenite. Unexpectedly, the mobilization of HuR to SGs was prevented through the activation of Janus kinase 3 (JAK3) by the vitamin K3 analog menadione. JAK3 phosphorylated HuR at tyrosine 200, in turn inhibiting HuR localization in SGs, reducing HuR interaction with targets SIRT1 and VHL mRNAs, and accelerating target mRNA decay. Our findings indicate that HuR is tyrosine-phosphorylated by JAK3, and link this modification to HuR subcytoplasmic localization and to the fate of HuR target mRNAs. C1 [Yoon, Je-Hyun; Abdelmohsen, Kotb; Srikantan, Subramanya; Guo, Rong; Yang, Xiaoling; Martindale, Jennifer L.; Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Abdelmohsen, K (reprint author), NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM abdelmohsenk@mail.nih.gov; gorospem@grc.nia.nih.gov FU National Institute on Aging-Intramural Research Program, National Institutes of Health FX Funding for open access charge: National Institute on Aging-Intramural Research Program, National Institutes of Health. NR 40 TC 18 Z9 19 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS 2 BP 1196 EP 1208 DI 10.1093/nar/gkt903 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5KS UT WOS:000331138100047 PM 24106086 ER PT J AU Acland, A Agarwala, R Barrett, T Beck, J Benson, DA Bollin, C Bolton, E Bryant, SH Canese, K Church, DM Clark, K DiCuccio, M Dondoshansky, I Federhen, S Feolo, M Geer, LY Gorelenkov, V Hoeppner, M Johnson, M Kelly, C Khotomlianski, V Kimchi, A Kimelman, M Kitts, P Krasnov, S Kuznetsov, A Landsman, D Lipman, DJ Lu, ZY Madden, TL Madej, T Maglott, DR Marchler-Bauer, A Karsch-Mizrachi, I Murphy, T Ostell, J O'Sullivan, C Panchenko, A Phan, L Pruitt, DPKD Rubinstein, W Sayers, EW Schneider, V Schuler, GD Sequeira, E Sherry, ST Shumway, M Sirotkin, K Siyan, K Slotta, D Soboleva, A Soussov, V Starchenko, G Tatusova, TA Trawick, BW Vakatov, D Wang, YL Ward, MH Wilbur, WJ Yaschenko, E Zbicz, K AF Acland, Abigail Agarwala, Richa Barrett, Tanya Beck, Jeff Benson, Dennis A. Bollin, Colleen Bolton, Evan Bryant, Stephen H. Canese, Kathi Church, Deanna M. Clark, Karen DiCuccio, Michael Dondoshansky, Ilya Federhen, Scott Feolo, Michael Geer, Lewis Y. Gorelenkov, Viatcheslav Hoeppner, Marilu Johnson, Mark Kelly, Christopher Khotomlianski, Viatcheslav Kimchi, Avi Kimelman, Michael Kitts, Paul Krasnov, Sergey Kuznetsov, Anatoliy Landsman, David Lipman, David J. Lu, Zhiyong Madden, Thomas L. Madej, Tom Maglott, Donna R. Marchler-Bauer, Aron Karsch-Mizrachi, Ilene Murphy, Terence Ostell, James O'Sullivan, Christopher Panchenko, Anna Phan, Lon Pruitt, Don Preussm Kim D. Rubinstein, Wendy Sayers, Eric W. Schneider, Valerie Schuler, Gregory D. Sequeira, Edwin Sherry, Stephen T. Shumway, Martin Sirotkin, Karl Siyan, Karanjit Slotta, Douglas Soboleva, Alexandra Soussov, Vladimir Starchenko, Grigory Tatusova, Tatiana A. Trawick, Bart W. Vakatov, Denis Wang, Yanli Ward, Minghong Wilbur, W. John Yaschenko, Eugene Zbicz, Kerry CA NCBI Resource Coordinators TI Database resources of the National Center for Biotechnology Information SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ONLINE MENDELIAN INHERITANCE; BIOLOGICAL PATHWAYS; GENE ONTOLOGY; NCBI; SEQUENCES; GENOMES; SEARCH; SYSTEM; TOOL; ANNOTATION AB In addition to maintaining the GenBank (R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI, http://www.ncbi.nlm.nih.gov) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI Web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central, PubReader, Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link, Primer-BLAST, COBALT, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, dbVar, Epigenomics, the Genetic Testing Registry, Genome and related tools, the Map Viewer, Trace Archive, Sequence Read Archive, BioProject, BioSample, ClinVar, MedGen, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus, Probe, Online Mendelian Inheritance in Animals, the Molecular Modeling Database, the Conserved Domain Database, the Conserved Domain Architecture Retrieval Tool, Biosystems, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All these resources can be accessed through the NCBI home page. C1 [Sayers, Eric W.; NCBI Resource Coordinators] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Sayers, EW (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM sayers@ncbi.nlm.nih.gov RI Geer, Lewis/H-2714-2014; OI Trawick, Bart/0000-0002-3635-3508; Marchler-Bauer, Aron/0000-0003-1516-0712; Landsman, David/0000-0002-9819-6675 FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 61 TC 129 Z9 131 U1 6 U2 39 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS D1 BP D7 EP D17 DI 10.1093/nar/gkt1146 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5LF UT WOS:000331139800002 ER PT J AU Benson, DA Clark, K Karsch-Mizrachi, I Lipman, DJ Ostell, J Sayers, EW AF Benson, Dennis A. Clark, Karen Karsch-Mizrachi, Ilene Lipman, David J. Ostell, James Sayers, Eric W. TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DATABASE; ARCHIVE; GROWTH AB GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for over 280 000 formally described species. These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and GenBank staff assign accession numbers upon data receipt. Daily data exchange with the European Nucleotide Archive and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through the National Center for Biotechnology Information (NCBI) Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI home page: www.ncbi.nlm.nih.gov. C1 [Benson, Dennis A.; Clark, Karen; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Sayers, Eric W.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Sayers, EW (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM sayers@ncbi.nlm.nih.gov FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 12 TC 136 Z9 141 U1 4 U2 42 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS D1 BP D32 EP D37 DI 10.1093/nar/gkt1030 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5LF UT WOS:000331139800005 PM 24217914 ER PT J AU Brister, JR Bao, YM Zhdanov, SA Ostapchuck, Y Chetvernin, V Kiryutin, B Zaslavsky, L Kimelman, M Tatusova, TA AF Brister, J. Rodney Bao, Yiming Zhdanov, Sergey A. Ostapchuck, Yuri Chetvernin, Vyacheslav Kiryutin, Boris Zaslavsky, Leonid Kimelman, Michael Tatusova, Tatiana A. TI Virus Variation Resource-recent updates and future directions SO NUCLEIC ACIDS RESEARCH LA English DT Article ID WEST NILE VIRUS; BIOTECHNOLOGY INFORMATION; NATIONAL CENTER; EVOLUTION; DENGUE; DYNAMICS; AMERICA AB Virus Variation (http://www.ncbi.nlm.nih.gov/genomes/VirusVariation/) is a comprehensive, we-bbased resource designed to support the retrieval and display of large virus sequence datasets. The resource includes a value added database, a specialized search interface and a suite of sequence data displays. Virus-specific sequence annotation and database loading pipelines produce consistent protein and gene annotation and capture sequence descriptors from sequence records then map these metadata to a controlled vocabulary. The database supports a metadata driven, web-based search interface where sequences can be selected using a variety of biological and clinical criteria. Retrieved sequences can then be downloaded in a variety of formats or analyzed using a suite of tools and displays. Over the past 2 years, the pre-existing influenza and Dengue virus resources have been combined into a single construct and West Nile virus added to the resultant resource. A number of improvements were incorporated into the sequence annotation and database loading pipelines, and the virus-specific search interfaces were updated to support more advanced functions. Several new features have also been added to the sequence download options, and a new multiple sequence alignment viewer has been incorporated into the resource tool set. Together these enhancements should support enhanced usability and the inclusion of new viruses in the future. C1 [Brister, J. Rodney; Bao, Yiming; Zhdanov, Sergey A.; Ostapchuck, Yuri; Chetvernin, Vyacheslav; Kiryutin, Boris; Zaslavsky, Leonid; Kimelman, Michael; Tatusova, Tatiana A.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Brister, JR (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM jamesbr@ncbi.nlm.nih.gov FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 16 TC 15 Z9 15 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS D1 BP D660 EP D665 DI 10.1093/nar/gkt1268 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5LF UT WOS:000331139800097 PM 24304891 ER PT J AU Farrell, CM O'Leary, NA Harte, RA Loveland, JE Wilming, LG Wallin, C Diekhans, M Barrell, D Searle, SMJ Aken, B Hiatt, SM Frankish, A Suner, MM Rajput, B Steward, CA Brown, GR Bennett, R Murphy, M Wu, W Kay, MP Hart, J Rajan, J Weber, J Snow, C Riddick, LD Hunt, T Webb, D Thomas, M Tamez, P Rangwala, SH McGarvey, KM Pujar, S Shkeda, A Mudge, JM Gonzalez, JM Gilbert, JGR Trevanion, SJ Baertsch, R Harrow, JL Hubbard, T Ostell, JM Haussler, D Pruitt, KD AF Farrell, Catherine M. O'Leary, Nuala A. Harte, Rachel A. Loveland, Jane E. Wilming, Laurens G. Wallin, Craig Diekhans, Mark Barrell, Daniel Searle, Stephen M. J. Aken, Bronwen Hiatt, Susan M. Frankish, Adam Suner, Marie-Marthe Rajput, Bhanu Steward, Charles A. Brown, Garth R. Bennett, Ruth Murphy, Michael Wu, Wendy Kay, Mike P. Hart, Jennifer Rajan, Jeena Weber, Janet Snow, Catherine Riddick, Lillian D. Hunt, Toby Webb, David Thomas, Mark Tamez, Pamela Rangwala, Sanjida H. McGarvey, Kelly M. Pujar, Shashikant Shkeda, Andrei Mudge, Jonathan M. Gonzalez, Jose M. Gilbert, James G. R. Trevanion, Stephen J. Baertsch, Robert Harrow, Jennifer L. Hubbard, Tim Ostell, James M. Haussler, David Pruitt, Kim D. TI Current status and new features of the Consensus Coding Sequence database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENOME ANNOTATION; PROJECT; EXPRESSION; ELEMENTS AB The Consensus Coding Sequence (CCDS) project (http://www.ncbi.nlm.nih.gov/CCDS/) is a collaborative effort to maintain a dataset of protein-coding regions that are identically annotated on the human and mouse reference genome assemblies by the National Center for Biotechnology Information (NCBI) and Ensembl genome annotation pipelines. Identical annotations that pass quality assurance tests are tracked with a stable identifier (CCDS ID). Members of the collaboration, who are from NCBI, the Wellcome Trust Sanger Institute and the University of California Santa Cruz, provide coordinated and continuous review of the dataset to ensure high-quality CCDS representations. We describe here the current status and recent growth in the CCDS dataset, as well as recent changes to the CCDS web and FTP sites. These changes include more explicit reporting about the NCBI and Ensembl annotation releases being compared, new search and display options, the addition of biologically descriptive information and our approach to representing genes for which support evidence is incomplete. We also present a summary of recent and future curation targets. C1 [Farrell, Catherine M.; O'Leary, Nuala A.; Wallin, Craig; Hiatt, Susan M.; Rajput, Bhanu; Brown, Garth R.; Murphy, Michael; Wu, Wendy; Hart, Jennifer; Weber, Janet; Riddick, Lillian D.; Webb, David; Tamez, Pamela; Rangwala, Sanjida H.; McGarvey, Kelly M.; Pujar, Shashikant; Shkeda, Andrei; Ostell, James M.; Pruitt, Kim D.] NIH, Natl Biotechnol Ctr, Natl Lib Med, Bethesda, MD 20894 USA. [Harte, Rachel A.; Diekhans, Mark; Baertsch, Robert; Haussler, David] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. [Loveland, Jane E.; Wilming, Laurens G.; Barrell, Daniel; Searle, Stephen M. J.; Aken, Bronwen; Frankish, Adam; Suner, Marie-Marthe; Steward, Charles A.; Bennett, Ruth; Kay, Mike P.; Rajan, Jeena; Snow, Catherine; Hunt, Toby; Thomas, Mark; Mudge, Jonathan M.; Gonzalez, Jose M.; Gilbert, James G. R.; Trevanion, Stephen J.; Harrow, Jennifer L.; Hubbard, Tim] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Haussler, David] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA. RP Pruitt, KD (reprint author), NIH, Natl Biotechnol Ctr, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM pruitt@ncbi.nlm.nih.gov RI Hubbard, Tim/C-2567-2008; OI Hubbard, Tim/0000-0002-1767-9318; Hunt, Toby/0000-0001-8377-0841; Wilming, Laurens/0000-0002-4154-7358; Gilbert, James/0000-0001-8079-3159; Snow, Catherine/0000-0002-1672-3532; Gonzalez, Jose M/0000-0001-5569-0705; Aken, Bronwen/0000-0002-3032-4095; Trevanion, Stephen/0000-0002-4862-3333 FU National Institutes of Health, National Library of Medicine; National Human Genome Research Institute (NHGRI) under the Wellcome Trust Sanger Institute [10U41 HG007234-01, 2186-03]; Wellcome Trust [WT077198, WT062023]; National Human Genome Research Institute [5U54HG00455-04] FX Work performed at NCBI was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine; Work performed at UCSC was funded by the National Human Genome Research Institute (NHGRI) for the ENCODE project [prime award 10U41 HG007234-01 under subaward 2186-03 from the Wellcome Trust Sanger Institute]; Work performed at WTSI was funded by the Wellcome Trust [WT077198] for HAVANA, and by the Wellcome Trust [WT062023]; National Human Genome Research Institute [5U54HG00455-04] for Ensembl. Funding for open access charge: The Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 24 TC 56 Z9 56 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS D1 BP D865 EP D872 DI 10.1093/nar/gkt1059 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5LF UT WOS:000331139800126 PM 24217909 ER PT J AU Fernandez-Suarez, XM Rigden, DJ Galperin, MY AF Fernandez-Suarez, Xose M. Rigden, Daniel J. Galperin, Michael Y. TI The 2014 Nucleic Acids Research Database Issue and an updated NAR online Molecular Biology Database Collection SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The 2014 Nucleic Acids Research Database Issue includes descriptions of 58 new molecular biology databases and recent updates to 123 databases previously featured in NAR or other journals. For convenience, the issue is now divided into eight sections that reflect major subject categories. Among the highlights of this issue are six databases of the transcription factor binding sites in various organisms and updates on such popular databases as CAZy, Database of Genomic Variants (DGV), dbGaP, DrugBank, KEGG, miRBase, Pfam, Reactome, SEED, TCDB and UniProt. There is a strong block of structural databases, which includes, among others, the new RNA Bricks database, updates on PDBe, PDBsum, ArchDB, Gene3D, ModBase, Nucleic Acid Database and the recently revived iPfam database. An update on the NCBI's MMDB describes VAST+, an improved tool for protein structure comparison. Two articles highlight the development of the Structural Classification of Proteins (SCOP) database: one describes SCOPe, which automates assignment of new structures to the existing SCOP hierarchy; the other one describes the first version of SCOP2, with its more flexible approach to classifying protein structures. This issue also includes a collection of articles on bacterial taxonomy and metagenomics, which includes updates on the List of Prokaryotic Names with Standing in Nomenclature (LPSN), Ribosomal Database Project (RDP), the SILVA/LTP project and several new metagenomics resources. The NAR online Molecular Biology Database Collection, http://www.oxfordjournals.org/nar/database/c/, has been expanded to 1552 databases. The entire Database Issue is freely available online on the Nucleic Acids Research website (http://nar.oxfordjournals.org/). C1 [Fernandez-Suarez, Xose M.] Life Technol, Paisley PA4 9RF, Renfrew, Scotland. [Rigden, Daniel J.] Univ Liverpool, Inst Integrat Biol, Liverpool L69 7ZB, Merseyside, England. [Galperin, Michael Y.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM nardatabase@gmail.com OI Rigden, Daniel/0000-0002-7565-8937; Galperin, Michael/0000-0002-2265-5572 FU NIH Intramural Research Program at the National Library of Medicine; Oxford University Press FX NIH Intramural Research Program at the National Library of Medicine (to M.Y.G.). Funding for open access charge: Waived by Oxford University Press. NR 43 TC 36 Z9 38 U1 0 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS D1 BP D1 EP D6 DI 10.1093/nar/gkt1282 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5LF UT WOS:000331139800001 PM 24316579 ER PT J AU Landrum, MJ Lee, JM Riley, GR Jang, W Rubinstein, WS Church, DM Maglott, DR AF Landrum, Melissa J. Lee, Jennifer M. Riley, George R. Jang, Wonhee Rubinstein, Wendy S. Church, Deanna M. Maglott, Donna R. TI ClinVar: public archive of relationships among sequence variation and human phenotype SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ACMG RECOMMENDATIONS; EXOME AB ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/) provides a freely available archive of reports of relationships among medically important variants and phenotypes. ClinVar accessions submissions reporting human variation, interpretations of the relationship of that variation to human health and the evidence supporting each interpretation. The database is tightly coupled with dbSNP and dbVar, which maintain information about the location of variation on human assemblies. ClinVar is also based on the phenotypic descriptions maintained in MedGen (http://www.ncbi.nlm.nih.gov/medgen). Each ClinVar record represents the submitter, the variation and the phenotype, i.e. the unit that is assigned an accession of the format SCV000000000.0. The submitter can update the submission at any time, in which case a new version is assigned. To facilitate evaluation of the medical importance of each variant, ClinVar aggregates submissions with the same variation/phenotype combination, adds value from other NCBI databases, assigns a distinct accession of the format RCV000000000.0 and reports if there are conflicting clinical interpretations. Data in ClinVar are available in multiple formats, including html, download as XML, VCF or tab-delimited subsets. Data from ClinVar are provided as annotation tracks on genomic RefSeqs and are used in tools such as Variation Reporter (http://www.ncbi.nlm.nih.gov/variation/tools/reporter), which reports what is known about variation based on user-supplied locations. C1 [Landrum, Melissa J.; Lee, Jennifer M.; Riley, George R.; Jang, Wonhee; Rubinstein, Wendy S.; Church, Deanna M.; Maglott, Donna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Maglott, DR (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM maglott@ncbi.nlm.nih.gov FU National Institutes of Health, National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 14 TC 378 Z9 385 U1 2 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS D1 BP D980 EP D985 DI 10.1093/nar/gkt1113 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5LF UT WOS:000331139800144 PM 24234437 ER PT J AU MacArthur, JAL Morales, J Tully, RE Astashyn, A Gil, L Bruford, EA Larsson, P Flicek, P Dalgleish, R Maglott, DR Cunningham, F AF MacArthur, Jacqueline A. L. Morales, Joannella Tully, Ray E. Astashyn, Alex Gil, Laurent Bruford, Elspeth A. Larsson, Pontus Flicek, Paul Dalgleish, Raymond Maglott, Donna R. Cunningham, Fiona TI Locus Reference Genomic: reference sequences for the reporting of clinically relevant sequence variants SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MESSENGER-RNA; ANNOTATION; DATABASES; PROJECT; GUIDELINES; RESOURCES; MUTATIONS; TITIN AB Locus Reference Genomic (LRG; http://www.lrg-sequence.org/) records contain internationally recognized stable reference sequences designed specifically for reporting clinically relevant sequence variants. Each LRG is contained within a single file consisting of a stable 'fixed' section and a regularly updated 'updatable' section. The fixed section contains stable genomic DNA sequence for a genomic region, essential transcripts and proteins for variant reporting and an exon numbering system. The updatable section contains mapping information, annotation of all transcripts and overlapping genes in the region and legacy exon and amino acid numbering systems. LRGs provide a stable framework that is vital for reporting variants, according to Human Genome Variation Society (HGVS) conventions, in genomic DNA, transcript or protein coordinates. To enable translation of information between LRG and genomic coordinates, LRGs include mapping to the human genome assembly. LRGs are compiled and maintained by the National Center for Biotechnology Information (NCBI) and European Bioinformatics Institute (EBI). LRG reference sequences are selected in collaboration with the diagnostic and research communities, locus-specific database curators and mutation consortia. Currently >700 LRGs have been created, of which >400 are publicly available. The aim is to create an LRG for every locus with clinical implications. C1 [MacArthur, Jacqueline A. L.; Morales, Joannella; Gil, Laurent; Bruford, Elspeth A.; Larsson, Pontus; Flicek, Paul; Cunningham, Fiona] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England. [Tully, Ray E.; Astashyn, Alex; Maglott, Donna R.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Dalgleish, Raymond] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. RP Cunningham, F (reprint author), European Bioinformat Inst, European Mol Biol Lab, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England. EM fiona@ebi.ac.uk OI Bruford, Elspeth/0000-0002-8380-5247; Flicek, Paul/0000-0002-3897-7955 FU Wellcome Trust [WT095908]; British Heart Foundation [SP/10/10/28431]; European Molecular Biology Laboratory; European Community [200754]; National Institutes of Health; National Library of Medicine FX The Wellcome Trust [WT095908]; British Heart Foundation [SP/10/10/28431]; European Molecular Biology Laboratory. European Community's Seventh Framework Programme [FP7/2007-2013] under grant agreement number 200754-the GEN2PHEN project. Work at NCBI is supported by the National Institutes of Health Intramural Research Program and the National Library of Medicine. Funding for open access charge: The Wellcome Trust. NR 25 TC 17 Z9 17 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2014 VL 42 IS D1 BP D873 EP D878 DI 10.1093/nar/gkt1198 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AA5LF UT WOS:000331139800127 PM 24285302 ER EF