FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kucharski, AJ Mills, HL Donnelly, CA Riley, S AF Kucharski, Adam J. Mills, Harriet L. Donnelly, Christl A. Riley, Steven TI Transmission Potential of Influenza A(H7N9) Virus, China, 2013-2014 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID LIVE-POULTRY MARKETS; INFECTION AB To determine transmission potential of influenza A(H7N9) virus, we used symptom onset data to compare 2 waves of infection in China during 2013-2014. We found evidence of increased transmission potential in the second wave and showed that live bird market closure was significantly less effective in Guangdong than in other regions. C1 [Kucharski, Adam J.] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England. [Kucharski, Adam J.] NIH, Bethesda, MD 20892 USA. [Kucharski, Adam J.; Mills, Harriet L.; Donnelly, Christl A.; Riley, Steven] Univ London Imperial Coll Sci Technol & Med, London, England. RP Kucharski, AJ (reprint author), Univ London London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, Keppel St, London WC1E 7HT, England. EM adam.kucharski@lshtm.ac.uk OI Donnelly, Christl/0000-0002-0195-2463 FU Wellcome Trust [093488/Z/10/Z]; Medical Research Council (United Kingdom) [MR/J008761/1, MR/K021524/1]; National Institute for General Medical Sciences (United States) [MIDAS U01 GM110721-01]; European Union Seventh Framework Programme [278433-PREDEMICS]; Fogarty International Center (United States) [R01 TW008246-01]; Research and Policy for Infectious Disease Dynamics program from Fogarty International Center with the Science and Technology Directorate, Department of Homeland Security. FX This work was funded by the Wellcome Trust (project grant 093488/Z/10/Z); the Medical Research Council (United Kingdom, project grant MR/J008761/1; Fellowship MR/K021524/1); National Institute for General Medical Sciences (United States, MIDAS U01 GM110721-01); the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 278433-PREDEMICS; the Fogarty International Center (United States, R01 TW008246-01); and the Research and Policy for Infectious Disease Dynamics program also from Fogarty International Center with the Science and Technology Directorate, Department of Homeland Security. NR 14 TC 7 Z9 8 U1 0 U2 8 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAY PY 2015 VL 21 IS 5 BP 852 EP 855 DI 10.3201/eid2105.141137 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CG9BW UT WOS:000353610400016 PM 25897624 ER PT J AU Prescott, J Bushmaker, T Fischer, R Miazgowicz, K Judson, S Munster, VJ AF Prescott, Joseph Bushmaker, Trenton Fischer, Robert Miazgowicz, Kerri Judson, Seth Munster, Vincent J. TI Postmortem Stability of Ebola Virus SO EMERGING INFECTIOUS DISEASES LA English DT Article ID HEMORRHAGIC-FEVER; CONGO; TRANSMISSION; RISK AB The ongoing Ebola virus outbreak in West Africa has highlighted questions regarding stability of the virus and detection of RNA from corpses. We used Ebola virus infected macaques to model humans who died of Ebola virus disease. Viable virus was isolated <= 7 days posteuthanasia; viral RNA was detectable for 10 weeks. C1 [Prescott, Joseph; Bushmaker, Trenton; Fischer, Robert; Miazgowicz, Kerri; Judson, Seth; Munster, Vincent J.] NIH, Hamilton, MT USA. RP Munster, VJ (reprint author), NIAID, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM munstervj@niaid.nih.gov OI Fischer, Robert/0000-0002-1816-472X; Munster, Vincent/0000-0002-2288-3196 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This study was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 12 TC 21 Z9 21 U1 1 U2 19 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAY PY 2015 VL 21 IS 5 BP 856 EP 859 DI 10.3201/eid2105.150041 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CG9BW UT WOS:000353610400017 PM 25897646 ER PT J AU Bae, WK Kang, K Yu, JH Yoo, KH Factor, VM Kaji, K Matter, M Thorgeirsson, S Hennighausen, L AF Bae, Woo Kyun Kang, Keunsoo Yu, Ji Hoon Yoo, Kyung Hyun Factor, Valentina M. Kaji, Kosuke Matter, Matthias Thorgeirsson, Snorri Hennighausen, Lothar TI The methyltransferases enhancer of zeste homolog (EZH) 1 and EZH2 control hepatocyte homeostasis and regeneration SO FASEB JOURNAL LA English DT Article DE H3-K27 trimethylation; liver regeneration; fibrosis ID STEM-CELLS; GROUP PROTEINS; POLYCOMB; COMPLEX; CANCER; LIVER; PROLIFERATION; METHYLATION; MEMORY; BMI-1 AB To investigate the role of enhancer of zeste homolog (EZH) 1 and EZH2 in liver homeostasis, mice were generated that carried Ezh1(-/-) and EZH2(fl/fl) alleles and an Alb-Cre transgene. Only the combined loss of EZH1 and EZH2 in mouse hepatocytes caused a depletion of global trimethylation on Lys 27 of histone H3 (H3K27me3) marks and the specific loss of over similar to 1900 genes at 3 mo of age. Ezh1(-/-),Ezh2(fl/fl)Alb-Cre mice exhibited progressive liver abnormalities manifested by the development of regenerative nodules and concomitant periportal fibrosis, inflammatory infiltration, and activation of A6-positive hepatic progenitor cells at 8 mo of age. In response to chronic treatment with carbon tetrachloride, all experimental mice, but none of the controls (n = 27 each), showed increased hepatic degeneration associated with liver dysfunction and reduced ability to proliferate. After two-thirds partial hepatectomy, mutant mice (n = 5) displayed increased liver injury and a blunted regenerative response. Genome-wide analyses at 3 mo of age identified 51 genes that had lost H3K27me3 marks, and their expression was significantly increased. These genes were involved in regulation of cell survival, fibrosis, and proliferation. H3K27me3 levels and liver physiology were unaffected in mice lacking either EZH1 globally or EZH2 specifically in hepatocytes. This work demonstrates a critical redundancy of EZH1 and EZH2 in maintaining hepatic homeostasis and regeneration. C1 [Bae, Woo Kyun; Kang, Keunsoo; Yu, Ji Hoon; Yoo, Kyung Hyun; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, Bethesda, MD 20892 USA. [Factor, Valentina M.; Kaji, Kosuke; Matter, Matthias; Thorgeirsson, Snorri] NCI, Ctr Canc Res, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Bae, Woo Kyun] Chonnam Natl Univ, Sch Med, Dept Internal Med, Kwangju, South Korea. [Kang, Keunsoo] Dankook Univ, Dept Microbiol, Cheonan, South Korea. [Yu, Ji Hoon] Daegu Gyeongbuk Med Innovat Fdn, New Drug Dev Ctr, Taegu, South Korea. RP Bae, WK (reprint author), NIDDK, Lab Genet & Physiol, NIH, 8 Ctr Dri,Room 101, Bethesda, MD 20892 USA. EM drwookyun@chonnam.ac.kr; lotharh@mail.nih.gov FU NIH NIDDK FX The authors thank Harold Smith [U.S. National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases' (NIDDK) genomics core] for conducting next-generation sequencing. Alexander Tarakhovsky (Rockefeller University, New York, NY, USA) provided Ezh2 floxed mice. Ezh1 mutant mice were generated at the Research Institute of Molecular Pathology (Vienna, Austria) by Donal O'Carroll (laboratory of Thomas Jenuwein) with the help of Maria Sibilia (Laboratory of Erwin Wagner). The research was supported by the Intramural Research Program of the NIH NIDDK. The authors declare no conflicts of interest. NR 28 TC 5 Z9 5 U1 1 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 MAY PY 2015 VL 29 IS 5 BP 1653 EP 1662 DI 10.1096/fj.14-261537 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CH5ZJ UT WOS:000354114600005 PM 25477280 ER PT J AU Schenkel, LC Singh, RK Michel, V Zeisel, SH da Costa, KA Johnson, AR Mudd, HS Bakovic, M AF Schenkel, Laila C. Singh, Ratnesh K. Michel, Vera Zeisel, Steven H. da Costa, Kerry-Ann Johnson, Amy R. Mudd, Harvey S. Bakovic, Marica TI Mechanism of choline deficiency and membrane alteration in postural orthostatic tachycardia syndrome primary skin fibroblasts SO FASEB JOURNAL LA English DT Article DE choline transport; CTL1/SLC44A1; mitochondria; phospholipids ID TRANSPORTER-LIKE PROTEIN-1; RAT-LIVER MITOCHONDRIA; ONE-CARBON METABOLITES; MASS-SPECTROMETRY; S-ADENOSYLMETHIONINE; PHOSPHATIDYLETHANOLAMINE; CELLS; NUTRIENT; WOMEN; PHOSPHATIDYLCHOLINE AB Fibroblasts from a patient with postural orthostatic tachycardia syndrome (POTS), who presented with low plasma choline and betaine, were studied to determine the metabolic characteristics of the choline deficiency. Choline is required for the synthesis of the phospholipid phosphatidylcholine (PC) and for betaine, an important osmoregulator. Here, choline transport, lipid homeostasis, and mitochondria function were analyzed in skin fibroblasts from POTS and compared with control cells. The choline transporter-like protein 1/solute carrier 44A1 (CTL1/SLC44A1) and mRNA expression were 2-3 times lower in POTS fibroblasts, and choline uptake was reduced 60% (P < 0.05). Disturbances of membrane homeostasis were observed by reduced ratios between PC:phosphatidylethanolamine and sphingomyelin:cholesterol, as well as by modified phospholipid fatty acid composition. Choline deficiency also impaired mitochondria function, which was observed by a reduction in oxygen consumption, mitochondrial potential, and glycolytic activity. When POTS cells were treated with choline, transporter was up-regulated, and uptake of choline increased, offering an option for patient treatment. The characteristics of the POTS fibroblasts described here represent a first model of choline and CTL1/SLC44A1 deficiency, in which choline transport, membrane homeostasis, and mitochondrial function are impaired.Schenkel, L. C., Singh, R. K., Michel, V., Zeisel, S. H., da Costa, K.-A., Johnson, A. R., Mudd, H. S., Bakovic, M. Mechanism of choline deficiency and membrane alteration in postural orthostatic tachycardia syndrome primary skin fibroblasts. C1 [Schenkel, Laila C.; Singh, Ratnesh K.; Michel, Vera; Bakovic, Marica] Univ Guelph, Dept Human Hlth & Nutr Sci, Guelph, ON N1G 2W1, Canada. [Zeisel, Steven H.] Univ N Carolina, Inst Nutr Res, Kannapolis, NC USA. [Zeisel, Steven H.; Johnson, Amy R.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [da Costa, Kerry-Ann] Toxicol Serv Inc, Chapel Hill, NC USA. [Mudd, Harvey S.] NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bakovic, M (reprint author), Univ Guelph, Dept Human Hlth & Nutr Sci, Anim Sci & Nutr Bldg,Room 346,50 Stone Rd East, Guelph, ON N1G 2W1, Canada. EM mbakovic@uoguelph.ca OI Schenkel, Laila Cigana/0000-0003-4939-6790 FU National Sciences and Engineering Research Council of Canada; Ontario Ministry of Agriculture, Food and Rural Affairs FX All the authors wish to acknowledge Dr. Harvey S. Mudd (1927-2014) who assembled this team of scientists to examine the metabolic disorder presented in this paper in order to understand it and give the patient possible treatment options. Dr. Mudd was a thoughtful and generous collaborator, and this paper brings to fruition his tireless efforts, although he did not live to see its completion. The authors acknowledge the support of Michael Leadley and the Analytical Facility for Bioactive Molecules, Sick Kids Centre, Toronto, in assisting with the lipidomics analysis. This study was supported by operating grants from the National Sciences and Engineering Research Council of Canada and the Ontario Ministry of Agriculture, Food and Rural Affairs (to M.B.). NR 43 TC 1 Z9 1 U1 0 U2 2 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 MAY PY 2015 VL 29 IS 5 BP 1663 EP 1675 DI 10.1096/fj.14-258566 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CH5ZJ UT WOS:000354114600006 PM 25466896 ER PT J AU Deplanche, M El-Aouar, RA Alekseeva, L Ladier, E Jardin, J Henry, G Azevedo, V Miyoshi, A Beraud, L Laurent, F Lina, G Vandenesch, F Steghens, JP Le Loir, Y Otto, M Gotz, F Berkova, N AF Deplanche, Martine El-Aouar Filho, Rachid Aref Alekseeva, Ludmila Ladier, Emilie Jardin, Julien Henry, Gwenaele Azevedo, Vasco Miyoshi, Anderson Beraud, Laetitia Laurent, Frederic Lina, Gerard Vandenesch, Francois Steghens, Jean-Paul Le Loir, Yves Otto, Michael Goetz, Friedrich Berkova, Nadia TI Phenol-soluble modulin alpha induces G2/M phase transition delay in eukaryotic HeLa cells SO FASEB JOURNAL LA English DT Article DE Staphylococcus aureus; cell cycle alteration; defensins; toxin; innate immune response ID BETA-DEFENSIN 2; STAPHYLOCOCCUS-AUREUS; EPITHELIAL-CELLS; INFECTION; CYCLE; EXPRESSION; PROTEINS; INHIBIT; SKIN AB Staphylococcus aureus is a gram-positive bacterium responsible for a wide range of infections. Host cell cycle alteration is a sophisticated mechanism used by pathogens to hijack the defense functions of host cells. We previously demonstrated that S. aureus MW2 (USA400) bacteria induced a G2/M phase transition delay in HeLa cells. We demonstrate here that this activity is triggered by culture supernatant compounds. Using size exclusion chromatography of the MW2 supernatant, followed by mass spectroscopy analysis of corresponding peaks, we identified phenol-soluble modulin (PSM) peptides as the likely candidates for this effect. Indeed, synthetic PSM1 and PSM3 caused a G2/M phase transition delay. The implication of PSM in cell cycle alteration was confirmed by comparison of S. aureus Los Angeles County clone (LAC) wild-type with the isogenic mutant LACpsm, which lacks the psm operon encoding PSM1-4. PSM-induced G2/M transition delay correlated with a decrease in the defensin genes expression suggesting a diminution of antibacterial functions of epithelial cells. By testing the supernatant of S. aureus human clinical isolates, we found that the degree of G2/M phase transition delay correlated with PSM1 production. We show that PSMs secreted by S. aureus alter the host cell cycle, revealing a newly identified mechanism for fostering an infection. C1 [Deplanche, Martine; El-Aouar Filho, Rachid Aref; Alekseeva, Ludmila; Ladier, Emilie; Jardin, Julien; Henry, Gwenaele; Le Loir, Yves; Berkova, Nadia] INRA, STLO, UMR1253, Agrocampus Ouest, 65 Rue St Brieuc, F-35042 Rennes, France. [Deplanche, Martine; El-Aouar Filho, Rachid Aref; Alekseeva, Ludmila; Ladier, Emilie; Jardin, Julien; Henry, Gwenaele; Le Loir, Yves; Berkova, Nadia] Agrocampus Ouest, UMR1253, STLO, Rennes, France. [El-Aouar Filho, Rachid Aref; Azevedo, Vasco; Miyoshi, Anderson] Univ Fed Minas Gerais, Inst Ciencias Biol, Belo Horizonte, MG, Brazil. [Alekseeva, Ludmila] Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia. [Beraud, Laetitia; Laurent, Frederic; Lina, Gerard; Vandenesch, Francois] Univ Lyon 1, CNRS, INSERM U111, Ctr Int Rech Infectiol,Unite Mixtes Rech5308, F-69365 Lyon, France. [Laurent, Frederic; Lina, Gerard; Vandenesch, Francois; Steghens, Jean-Paul] Hosp Civil Lyon, Lyon, France. [Otto, Michael] NIH, Lab Human Bacterial Pathogenesis, Bethesda, MD 20892 USA. [Goetz, Friedrich] Univ Tubingen, Microbial Genet, Tubingen, Germany. RP Berkova, N (reprint author), INRA, STLO, UMR1253, Agrocampus Ouest, 65 Rue St Brieuc, F-35042 Rennes, France. EM nadia.berkova@rennes.inra.fr RI JARDIN, Julien/A-3241-2012; vasco, azevedo/F-4315-2011; Vandenesch, Francois/C-7209-2014 OI JARDIN, Julien/0000-0003-0520-9391; vasco, azevedo/0000-0002-4775-2280; Vandenesch, Francois/0000-0001-9412-7106 FU French National Institute for Agricultural Research (INRA) [P10552]; U.S. National Institutes of Health, National Institute of Allergy and Infectious Diseases' Intramural Research Program; German Research Foundation [SFB766]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES; Brazil); France-Russia Bilateral Collaboration FX The authors thank Gail Wagman and Mary Bret for revising the English. This work was supported by French National Institute for Agricultural Research (INRA), Ruminflame P10552 (to N.B., M.D., J.J., G.H., and Y.L.L.), the U.S. National Institutes of Health, National Institute of Allergy and Infectious Diseases' Intramural Research Program (to M.O.), and the German Research Foundation, SFB766 (to F.G.). R.A.E.-A.F. is a recipient of a Ph.D. fellowship from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES; Brazil), and L.A. is a recipient of a postdoctoral fellowship (France-Russia Bilateral Collaboration). The authors declare no conflicts of interest. NR 34 TC 6 Z9 6 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 MAY PY 2015 VL 29 IS 5 BP 1950 EP 1959 DI 10.1096/fj.14-260513 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CH5ZJ UT WOS:000354114600029 PM 25648996 ER PT J AU Eisenberg, ML Chen, Z Ye, AJ Louis, GMB AF Eisenberg, Michael L. Chen, Zhen Ye, Aijun Louis, Germaine M. Buck TI Relationship between physical occupational exposures and health on semen quality: data from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study SO FERTILITY AND STERILITY LA English DT Article DE Male infertility; oligospermia; workplace; comorbidity; health ID MALE-INFERTILITY; REPRODUCTIVE HORMONES; LIPID CONCENTRATIONS; DIABETES-MELLITUS; COUPLE FECUNDITY; UNITED-STATES; MEN; PREVALENCE; COHORT; MORTALITY AB Objective: To study the relationship among occupation, health, and semen quality in a cohort of men attempting to conceive. Design: Observational prospective cohort. Setting: Not applicable. Patient(s): A total of 501 couples discontinuing contraception were followed for 1 year while trying to conceive; 473 men (94%) provided one semen sample, and 80% provided a second sample. Intervention(s): None. Main Outcome Measure(s): Semen data obtained through at-home semen collection with next-day analysis/quantification. Result(s): In all, complete data were available for 456 men, with a mean age of 31.8 years. Work-related heavy exertion was consistently associated with lower semen concentration and total sperm count. Thirteen percent of men who reported heavy exertion displayed oligospermia, compared with 6% who did not report workplace exertion. Shift work, night work, vibration, noise, heat, and prolonged sitting were not associated with semen quality. Men with high blood pressure had significantly lower strict morphology scores compared with normotensive men (17% vs. 21%). In contrast, hyperlipidemia, diabetes, and composite of total comorbidities were not associated with semen quality. The number of medications a man was taking as a proxy of health status was associated with semen quality. There was a negative association between number of medications and sperm count. Conclusion(s): A negative relationship among occupational exertion, hypertension, and the number of medications with semen quality was identified. As these are potentially modifiable factors, further research should determine whether treatment or cessation may improve male fecundity. (C) 2015 by American Society for Reproductive Medicine. C1 [Eisenberg, Michael L.] Stanford Univ, Dept Urol, Stanford, CA 94305 USA. [Eisenberg, Michael L.] Stanford Univ, Dept Obstet & Gynecol, Stanford, CA 94305 USA. [Chen, Zhen; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD USA. [Ye, Aijun] Glotec, Rockville, MD USA. RP Eisenberg, ML (reprint author), Stanford Univ, Sch Med, Dept Urol, 300 Pasteur Dr, Stanford, CA 94305 USA. EM eisenberg@stanford.edu OI Eisenberg, Michael/0000-0001-5482-0141; Buck Louis, Germaine/0000-0002-1774-4490 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [N01-HD-3-3355, N01-HD-3-3356, N01-HD-3-3358] FX Intramural research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract nos. N01-HD-3-3355, N01-HD-3-3356, and N01-HD-3-3358). NR 37 TC 8 Z9 9 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2015 VL 103 IS 5 BP 1271 EP 1277 DI 10.1016/j.fertnstert.2015.02.010 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CH2GM UT WOS:000353843700031 PM 25765658 ER PT J AU Rigler, SL Kay, DM Sicko, RJ Fan, RZ Liu, AY Caggana, M Browne, ML Druschel, CM Romitti, PA Brody, LC Mills, JL AF Rigler, Shannon L. Kay, Denise M. Sicko, Robert J. Fan, Ruzong Liu, Aiyi Caggana, Michele Browne, Marilyn L. Druschel, Charlotte M. Romitti, Paul A. Brody, Lawrence C. Mills, James L. TI Novel copy-number variants in a population-based investigation of classic heterotaxy SO GENETICS IN MEDICINE LA English DT Article DE BMP2 gene; congenital heart disease; copy-number variant; heterotaxy; MNDA gene ID CONGENITAL HEART-DISEASE; LEFT-RIGHT ASYMMETRY; ATRIOVENTRICULAR SEPTAL-DEFECTS; CARDIOVASCULAR MALFORMATIONS; MISSENSE MUTATIONS; HUMAN GENOME; GENE; ZEBRAFISH; MOUSE; IDENTIFICATION AB Purpose: Heterotaxy is a clinically and genetically heterogeneous disorder. We investigated whether screening cases restricted to a classic phenotype would result in the discovery of novel, potentially causal copy-number variants. Methods: We identified 77 cases of classic heterotaxy from all live births in New York State during 1998-2005. DNA extracted from each infant's newborn dried blood spot was genotyped with a microarray containing 2.5 million single-nucleotide polymorphisms. Copy-number variants were identified with PennCNV and cnvPartition software. Candidates were selected for follow-up if they were absent in unaffected controls, contained 10 or more consecutive probes, and had minimal overlap with variants published in the Database of Genomic Variants. Results: We identified 20 rare copy-number variants including a deletion of BMP2, which has been linked to laterality disorders in mice but not previously reported in humans. We also identified a large, terminal deletion of 10q and a microdeletion at 1q23.1 involving the MNDA gene; both are rare variants suspected to be associated with heterotaxy. Conclusion: Our findings implicate rare copy-number variants in classic heterotaxy and highlight several candidate gene regions for further investigation. We also demonstrate the efficacy of copy-number variant genotyping in blood spots using microarrays. C1 [Rigler, Shannon L.; Fan, Ruzong; Liu, Aiyi; Mills, James L.] Eunice Kennedy Shriver Natl Inst Hlth & Human Dev, Div Intramural Populat Hlth Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Rigler, Shannon L.] Walter Reed Natl Mil Med Ctr, Dept Neonatol, Bethesda, MD USA. [Kay, Denise M.; Sicko, Robert J.; Caggana, Michele] New York State Dept Hlth, Div Genet, Wadsworth Ctr, Albany, NY USA. [Browne, Marilyn L.; Druschel, Charlotte M.] New York State Dept Hlth, Congenital Malformat Registry, Albany, NY USA. [Browne, Marilyn L.; Druschel, Charlotte M.] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Rensselaer, NY USA. [Romitti, Paul A.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Rigler, SL (reprint author), Eunice Kennedy Shriver Natl Inst Hlth & Human Dev, Div Intramural Populat Hlth Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM shannon.rigler@med.navy.mil OI Liu, Aiyi/0000-0002-6618-5082 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN275201100001I, HHSN27500005]; National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [N01-DK-73431]; National Human Genome Research Institute; Wellcome Trust FX This work was funded by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts HHSN275201100001I and HHSN27500005; NICHD contract N01-DK-73431) and the National Human Genome Research Institute. Funding for the DECIPHER project was provided by the Wellcome Trust. We thank Michael Tsai and Natalie Weir at the Minnesota Core Laboratories and the staff at the Biomedical Genomics Center Facility at the University of Minnesota for microarray genotyping; Emily C. McGrath, Adam C. Gearhart, April J. Atkins, Deborah K. West, and Zoe Edmunds at the Wadsworth Center, New York State Department of Health, for Sanger sequencing and laboratory and technical assistance; Sandra D. Richardson at the Congenital Malformations Registry, New York State Department of Health, for data management; Matthew Shudt and Zhen Zhang at the Wadsworth Center Applied Genomic Technologies Core for next-generation sequencing; and Nathan Pankratz, University of Minnesota, and Karl G. Hill, Social Development Research Group, University of Washington, for generously sharing population B-allele frequency and GC content files for PennCNV software. This study makes use of data generated by the DECIPHER Consortium. A full list of centers that contributed to the generation of the data is available from http://decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk. Those who carried out the original analysis and collection of the data bear no responsibility for the further analysis or interpretation. Some data used for comparison in this article were obtained from the International Standards for Cytogenomic Arrays Consortium database (http://www.iscaconsortium.org), which generates this information using the National Center for Biotechnology Information's database of genomic structural variation (dbVar, http://www.ncbi.nlm.nih.gov/dbvar/), study nstd37. Samples and associated phenotype data were provided by International Standards for Cytogenomic Arrays Consortium member laboratories. NR 39 TC 6 Z9 6 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD MAY PY 2015 VL 17 IS 5 BP 348 EP 357 DI 10.1038/gim.2014.112 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA CH5SZ UT WOS:000354096900004 PM 25232849 ER PT J AU Lawrence, MG Uzel, G AF Lawrence, Monica G. Uzel, Gulbu TI 6-Year-Old Boy with Recurrent Sinopulmonary Infections and Lymphadenopathy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Editorial Material DE Hyper-IgM syndrome; Nodular lymphoid hyperplasia; Epstein-Barr virus (EBV); Cytomegalovirus (CMV); Activated p110 delta ID MUTATIONS; DEFICIENCY; IMMUNODEFICIENCY; PI3K; GENE C1 [Lawrence, Monica G.] Univ Virginia, Dept Med, Div Allergy Asthma & Immunol, Charlottesville, VA USA. [Uzel, Gulbu] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. RP Uzel, G (reprint author), NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. EM guzel@niaid.nih.gov FU Intramural NIH HHS NR 11 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD MAY-JUN PY 2015 VL 3 IS 3 BP 461 EP + DI 10.1016/j.jaip.2014.10.017 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA CH7JS UT WOS:000354212900031 PM 25956317 ER PT J AU Tykvart, J Barinka, C Svoboda, M Navratil, V Soucek, R Hubalek, M Hradilek, M Sacha, P Lubkowski, J Konvalinka, J AF Tykvart, Jan Barinka, Cyril Svoboda, Michal Navratil, Vaclav Soucek, Radko Hubalek, Martin Hradilek, Martin Sacha, Pavel Lubkowski, Jacek Konvalinka, Jan TI Structural and Biochemical Characterization of a Novel Aminopeptidase from Human Intestine SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLUTAMATE-CARBOXYPEPTIDASE-II; REACTION-MECHANISM; EXPRESSION; PEPTIDASE; CRYSTALLOGRAPHY; INHIBITION; PROTEINS; ENZYME; RAT AB N-acetylated alpha-linked acidic dipeptidase-like protein (NAALADase L), encoded by the NAALADL1 gene, is a close homolog of glutamate carboxypeptidase II, a metallopeptidase that has been intensively studied as a target for imaging and therapy of solid malignancies and neuropathologies. However, neither the physiological functions nor structural features of NAALADase L are known at present. Here, we report a thorough characterization of the protein product of the human NAALADL1 gene, including heterologous overexpression and purification, structural and biochemical characterization, and analysis of its expression profile. By solving the NAALADase L x-ray structure, we provide the first experimental evidence that it is a zinc-dependent metallopeptidase with a catalytic mechanism similar to that of glutamate carboxypeptidase II yet distinct substrate specificity. Aproteome-based assay revealed that the NAALADL1 gene product possesses previously unrecognized aminopeptidase activity but no carboxy-or endopeptidase activity. These findings were corroborated by site-directed mutagenesis and identification of bestatin as a potent inhibitor of the enzyme. Analysis of NAALADL1 gene expression at both the mRNA and protein levels revealed the small intestine as the major site of protein expression and points toward extensive alternative splicing of the NAALADL1 gene transcript. Taken together, our data imply that the NAALADL1 gene product's primary physiological function is associated with the final stages of protein/peptide digestion and absorption in the human digestive system. Based on these results, we suggest a new name for this enzyme: human ileal aminopeptidase (HILAP). C1 [Tykvart, Jan; Svoboda, Michal; Navratil, Vaclav; Soucek, Radko; Hubalek, Martin; Hradilek, Martin; Sacha, Pavel; Konvalinka, Jan] Acad Sci Czech Republic, Inst Organ Chem & Biochem, Gilead Sci & IOCB Res Ctr, CR-16610 Prague 6, Czech Republic. [Tykvart, Jan; Navratil, Vaclav; Sacha, Pavel; Konvalinka, Jan] Charles Univ Prague, Fac Nat Sci, Dept Biochem, Prague 2, Czech Republic. [Svoboda, Michal] Charles Univ Prague, Fac Nat Sci, Dept Phys & Macromol Chem, Prague 2, Czech Republic. [Barinka, Cyril] Acad Sci Czech Republic, Inst Biotechnol, Prague 4, Czech Republic. [Lubkowski, Jacek] NCI, Ctr Canc Res, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA. RP Konvalinka, J (reprint author), Acad Sci Czech Republic, Inst Organ Chem & Biochem, Vvi, Flemingovo 2, Prague 16610 6, Czech Republic. EM jan.konvalinka@uochb.cas.cz RI Barinka, Cyril/G-9803-2014; Hubalek, Martin/H-1400-2014; Tykvart, Jan/G-6770-2014; Sacha, Pavel/G-9729-2014; OI Tykvart, Jan/0000-0002-6938-1513; Sacha, Pavel/0000-0001-6198-9826; Konvalinka, Jan/0000-0003-0695-9266 FU Grant Agency of the Czech Republic [P304-12-0847]; InterBioMed Project from Ministry of Education of the Czech Republic [LO 1302]; National Institutes of Health, NCI, Center for Cancer Research, Intramural Research Program; European Regional Development Fund [CZ.1.05/1.1.00/02.0109]; United States Department of Energy [W-31-109-Eng38]; EMBO [1978, 249220] FX This work was supported by Grant Agency of the Czech Republic (Grant P304-12-0847) and InterBioMed Project LO 1302 from the Ministry of Education of the Czech Republic. This work was also supported in part by the National Institutes of Health, NCI, Center for Cancer Research, Intramural Research Program (to J. L.) and also in part by project "BIOCEV" (CZ.1.05/1.1.00/02.0109) from the European Regional Development Fund (to C. B.). The use of the Advanced Photon Source was supported by United States Department of Energy Contract W-31-109-Eng38.; Supported by EMBO Installation Grant 1978 and Installation Research Grant Project 249220. NR 31 TC 2 Z9 2 U1 2 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 1 PY 2015 VL 290 IS 18 BP 11321 EP 11336 DI 10.1074/jbc.M114.628149 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CH0OA UT WOS:000353719400010 PM 25752612 ER PT J AU Wang, SM Yin, LY Zhang, Y Fan, JH Chang, IJ Dawsey, SM Taylor, PR Abnet, CC Qiao, YL AF Wang, Shao-Ming Yin, Liang-Yu Zhang, Yu Fan, Jin-Hu Chang, Irene J. Dawsey, Sanford M. Taylor, Philip R. Abnet, Christian C. Qiao, You-Lin TI Multivitamin and mineral supplementation is associated with the reduction of fracture risk and hospitalization rate in Chinese adult males: a randomized controlled study SO JOURNAL OF BONE AND MINERAL METABOLISM LA English DT Article DE Multivitamin supplementation; Fracture risk; Hospitalization rate; Nutritional intervention trial ID VITAMIN-D SUPPLEMENTATION; OSTEOPOROSIS-RELATED FRACTURES; HIP-FRACTURES; GASTRIC CANCERS; ELDERLY-WOMEN; WORLDWIDE PREVALENCE; POSTMENOPAUSAL WOMEN; CONTROLLED-TRIAL; ESOPHAGEAL; CALCIUM AB Controversy exists in the literature regarding the efficacy of bone health-related nutrients, especially calcium and vitamin D, in preventing fractures. The aim of our present study was to determine the effect of multivitamin and mineral supplementation on fracture incidence among 3,318 participants from a nutritional intervention trial in Linxian, China. A total of 1,461 men and 1,857 women were enrolled and randomized to daily supplementation with 26 vitamins and minerals tablet or placebo pills for 6 years, followed by a 16-year post-interventional follow-up. The dates, sites, and causes of the fractures were collected retrospectively via a standardized questionnaire. Cox proportional hazard model was used to estimate hazard ratios and 95 % confidence intervals of fracture incidence in the intervention versus the placebo group. A total of 221 fractures (57 in men and 164 in women) occurred during the entire study period of 21 years and 9 months. In men, the supplement reduced the risk of fracture by 63 % during the trial period, and this protective effect was sustained and statistically significant when analysis included both the trial period and 5- or 10-year post-intervention follow-up (years 0-11, P = 0.04; years 0-16, P = 0.02, respectively). The protection against fracture was not apparent > 10 years after cessation of the intervention. In women, no significant effect of supplementation on fracture incidence was seen in any of the study periods. These results demonstrate that a 6-year multivitamin and mineral intervention was associated with significant reduction of fracture risk and fracture-related hospitalization in men, but not in women. C1 [Wang, Shao-Ming; Yin, Liang-Yu; Zhang, Yu; Fan, Jin-Hu; Qiao, You-Lin] Chinese Acad Med Sci, Canc Inst Hosp, Dept Epidemiol, Beijing 100021, Peoples R China. [Chang, Irene J.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Dawsey, Sanford M.; Taylor, Philip R.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Abnet, Christian C.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Qiao, YL (reprint author), Chinese Acad Med Sci, Canc Inst Hosp, Dept Epidemiol, 17 South Panjiayuan Lane, Beijing 100021, Peoples R China. EM abnetc@mail.nih.gov; qiaoy@cicams.ac.cn RI Abnet, Christian/C-4111-2015; Qiao, You-Lin/B-4139-2012 OI Abnet, Christian/0000-0002-3008-7843; Qiao, You-Lin/0000-0001-6380-0871 FU NIH [NHHSN261200477001C]; Cancer Institute of the Chinese Academy of Medical Sciences; Chinese Academy of Medical Sciences; Intramural Research Program of the US National Cancer Institute, NIH FX Shao-Ming Wang was involved in the writing and revising of the manuscript and part of the data analysis, Liang-Yu Yin was involved in the writing and revising of the manuscript, Zhang Yu was involved in the study design, data collection, data analysis and writing of the manuscript, and Jin-Hu Fan was involved in the study design, data collection and data analysis. Irene J. Chang was involved in revising the draft. Sanford M. Dawsey and Philip R. Taylor participated in the study design, data-analysis and revision of the manuscript, and Christian C. Abnet and You-Lin Qiao supervised the entire study as the principle investigators. All the authors contributed to the data interpretation and manuscript revisions and approved the final version of the manuscript. This study was supported in part by NIH contracts NHHSN261200477001C with the Cancer Institute of the Chinese Academy of Medical Sciences; by additional funds from the Chinese Academy of Medical Sciences; and by funds from the Intramural Research Program of the US National Cancer Institute, NIH. NR 49 TC 0 Z9 0 U1 1 U2 9 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0914-8779 EI 1435-5604 J9 J BONE MINER METAB JI J. Bone Miner. Metab. PD MAY PY 2015 VL 33 IS 3 BP 294 EP 302 DI 10.1007/s00774-014-0589-3 PG 9 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA CH8OH UT WOS:000354295200007 PM 24849736 ER PT J AU Mehta, GU Montgomery, BK Raghavan, P Sharma, S Nieman, LK Patronas, N Oldfield, EH Chittiboina, P AF Mehta, Gautam U. Montgomery, Blake K. Raghavan, Pooja Sharma, Susmeeta Nieman, Lynnette K. Patronas, Nicholas Oldfield, Edward H. Chittiboina, Prashant TI Different imaging characteristics of concurrent pituitary adenomas in a patient with Cushing's disease SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Cushing's disease; Delayed MRI; Fluid attenuated inversion recovery imaging; Pituitary adenoma; Transsphenoidal surgery ID SERIES; BRAIN; GLAND AB We report a patient with Cushing's disease (CD) and two pituitary adenomas that demonstrated different imaging characteristics and therefore suggest an alternative imaging strategy for these patients. A 42-year-old woman presented with signs and symptoms of CD. Biochemical evaluation confirmed hypercortisolemia and suggested CD. On pituitary MRI with spoiled gradient recalled acquisition in the steady-state and T1-weighted spin echo protocols, a 5 mm hypoenhancing region typical for a pituitary adenoma was identified on the left. However, after surgical resection the patient remained hypercortisolemic and pathology revealed a non-functional adenoma. At early repeat surgical exploration a 10 mm adenoma was found in the right side of the gland. Postoperatively the patient became hypocortisolemic and pathology demonstrated an adrenocorticotropic hormone (ACTH)-staining adenoma. On review of the initial MRI this tumor corresponded to a region of contrast retention best visualized on delayed fluid attenuated inversion recovery (FLAIR) imaging. While the incidentaloma in this case demonstrated classical imaging characteristics of a pituitary adenoma the larger ACTH-secreting tumor was best appreciated by contrast retention. This suggests a role for delayed postcontrast FLAIR imaging in the preoperative evaluation of CD. ACTH-secreting tumors causing CD cause significant morbidity. Due to their small size, a pituitary adenoma is frequently not identified on imaging despite endocrinologic testing suggesting CD. Regardless of improvements in MRI, many tumors are only identified at surgical exploration. Published by Elsevier Ltd. C1 [Mehta, Gautam U.; Montgomery, Blake K.; Oldfield, Edward H.; Chittiboina, Prashant] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20814 USA. [Raghavan, Pooja; Sharma, Susmeeta; Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Reprod Endocrinol, NIH, Bethesda, MD USA. [Patronas, Nicholas] NIH, Diagnost Radiol, Walter Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Oldfield, Edward H.] Univ Virginia, Hlth Sci Ctr, Dept Neurosurg, Charlottesville, VA 22908 USA. RP Chittiboina, P (reprint author), NINDS, Surg Neurol Branch, NIH, Room 3D20,10 Ctr Dr, Bethesda, MD 20814 USA. EM prashant.chittiboina@nih.gov OI Mehta, Gautam/0000-0002-8009-6430 FU Intramural Research Program of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health (NIH); NIH Medical Research Scholars Program - NIH FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health (NIH) and through the 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 Doris Duke Charitable Foundation, The Alexandria Real Estate Equities, Inc. and Mr. and Mrs. Joel S. Marcus, and the Howard Hughes Medical Institute, as well as other private donors. NR 14 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD MAY PY 2015 VL 22 IS 5 BP 891 EP 894 DI 10.1016/j.jocn.2015.01.001 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CH3KL UT WOS:000353929500021 PM 25827866 ER PT J AU Kubagawa, H Carroll, MC Jacob, CO Lang, KS Lee, KH Mak, T McAndrews, M Morse, HC Nolan, GP Ohno, H Richter, GH Seal, R Wang, JY Wiestner, A Coligan, JE AF Kubagawa, Hiromi Carroll, Michael C. Jacob, Chaim O. Lang, Karl S. Lee, Kyeong-Hee Mak, Tak McAndrews, Monica Morse, Herbert C., III Nolan, Garry P. Ohno, Hiroshi Richter, Guenther H. Seal, Ruth Wang, Ji-Yang Wiestner, Adrian Coligan, John E. TI Nomenclature of Toso, Fas Apoptosis Inhibitory Molecule 3, and IgM FcR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MU-R; IMMUNE-RESPONSES; T-CELLS; DENDRITIC CELLS; B-CELLS; RECEPTOR; ACTIVATION; BINDING; DEATH; GRANULOCYTES AB Hiromi Kubagawa and John E. Coligan coordinated an online meeting to define an appropriate nomenclature for the cell surface glycoprotein presently designated by different names: Toso, Fas apoptosis inhibitory molecule 3 (FAIM3), and IgM FcR (Fc mu R). FAIM3 and Faim3 are the currently approved symbols for the human and mouse genes, respectively, in the National Center for Biotechnology Information, Ensembl, and other databases. However, recent functional results reported by several groups of investigators strongly support a recommendation for renaming FAIM3/Faim3 as FCMR/Fcmr, a name better reflecting its physiological function as the FcR for IgM. Participants included 12 investigators involved in studying Toso/FAIM3(Faim3)/F mu R, representatives from the Human Genome Nomenclature Committee (Ruth Seal) and the Mouse Genome Nomenclature Committee (Monica McAndrews), and an observer from the IgM research field (Michael Carroll). In this article, we provide a brief background of the key research on the Toso/FAIM3(Faim3)/Fc mu R proteins, focusing on the ligand specificity and functional activity, followed by a brief summary of discussion about adopting a single name for this molecule and its gene and a resulting recommendation for genome nomenclature committees. C1 [Kubagawa, Hiromi] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Jacob, Chaim O.] Univ So Calif, Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Lang, Karl S.] Univ Duisburg Essen, Inst Immunol, D-45147 Essen, Germany. [Lee, Kyeong-Hee] Hannover Med Sch, Inst Clin Chem, D-30625 Hannover, Germany. [Mak, Tak] Univ Hlth Network, Princess Margaret Canc Ctr, Campbell Family Inst Breast Canc Res, Toronto, ON M5T 2M9, Canada. [McAndrews, Monica] Jackson Lab, Mouse Genome Informat, Bar Harbor, ME 04609 USA. [Morse, Herbert C., III; Coligan, John E.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Nolan, Garry P.] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA. [Ohno, Hiroshi] RIKEN, Ctr Integrat Med Sci, Lab Intestinal Ecosyst, Yokohama, Kanagawa 2300045, Japan. [Richter, Guenther H.] Tech Univ Munich, Klinikum Rechts Isar, Kinderklin, D-81664 Munich, Germany. [Seal, Ruth] European Bioinformat Inst, Human Genome Org Gene Nomenclature Comm, Hinxton CB10 1SD, Cambs, England. [Wang, Ji-Yang] Fudan Univ, Sch Basic Med Sci, Dept Immunol, Shanghai 200032, Peoples R China. [Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Kubagawa, H (reprint author), Deutsch Rheuma Forschungszentrum Berlin, Charitepl, D-10117 Berlin, Germany. EM hiromi.kubagawa@drfz.de; JCOLIGAN@niaid.nih.gov RI Ohno, Hiroshi/L-7899-2014; Lang, Karl/R-2505-2016; OI Ohno, Hiroshi/0000-0001-8776-9661; Seal, Ruth/0000-0002-7545-6817 FU National Institutes of Health/National Institute of Allergy and Infectious Diseases [R21AI094625]; National Human Genome Research Institute [U41HG003345]; Wellcome Trust [099129/Z/12/Z] FX This work was supported in part by National Institutes of Health/National Institute of Allergy and Infectious Diseases Grant R21AI094625 (to H.K.), the National Institutes of Health/National Institute of Allergy and Infectious Diseases Intramural Research Programs (to H.C.M. and J.E.C.), and National Human Genome Research Institute Grant U41HG003345 and Wellcome Trust Grant 099129/Z/12/Z (to R.S.). NR 24 TC 1 Z9 1 U1 2 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 IS 9 BP 4055 EP 4057 DI 10.4049/jimmunol.1500222 PG 3 WC Immunology SC Immunology GA CH0QN UT WOS:000353727400001 PM 25888699 ER PT J AU Wang, J Shirota, Y Bayik, D Shirota, H Tross, D Gulley, JL Wood, LV Berzofsky, JA Klinman, DM AF Wang, Jing Shirota, Yuko Bayik, Defne Shirota, Hidekazu Tross, Debra Gulley, James L. Wood, Lauren V. Berzofsky, Jay A. Klinman, Dennis M. TI Effect of TLR Agonists on the Differentiation and Function of Human Monocytic Myeloid-Derived Suppressor Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-ASSOCIATED MACROPHAGES; CARCINOMA PATIENTS; IMMUNE-RESPONSE; T-CELLS; IMMUNOSUPPRESSIVE ACTIVITY; ANTITUMOR IMMUNITY; INNATE IMMUNITY; CANCER-PATIENTS; IN-VIVO; ACTIVATION AB Tumors persist by occupying immunosuppressive microenvironments that inhibit the activity of tumoricidal T and NK cells. Monocytic myeloid-derived suppressor cells (mMDSC) are an important component of this immunosuppressive milieu. We find that the suppressive activity of mMDSC isolated from cancer patients can be reversed by treatment with TLR7/8 agonists, which induce human mMDSC to differentiate into tumoricidal M1-like macrophages. In contrast, agonists targeting TLR1/2 cause mMDSC to mature into immunosuppressive M2-like macrophages. These two populations of macrophage are phenotypically and functionally discrete and differ in gene expression profile. The ability of TLR7/8 agonists to reverse mMDSC-mediated immune suppression suggests that they might be useful adjuncts for tumor immunotherapy. C1 [Wang, Jing; Shirota, Yuko; Bayik, Defne; Shirota, Hidekazu; Tross, Debra; Klinman, Dennis M.] NCI, Canc & Inflammat Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Gulley, James L.] NCI, Genitourinary Malignancies Branch, Bethesda, MD 20892 USA. [Wood, Lauren V.; Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), Frederick Natl Lab Canc Res, Bldg 567,Room 205, Frederick, MD 21702 USA. EM klinmand@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS [Z01 BC010852-01] NR 56 TC 5 Z9 5 U1 1 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 IS 9 BP 4215 EP 4221 DI 10.4049/jimmunol.1402004 PG 7 WC Immunology SC Immunology GA CH0QN UT WOS:000353727400020 PM 25825448 ER PT J AU Ding, XL Yan, YP Li, X Li, K Ciric, B Yang, JX Zhang, Y Wu, S Xu, H Chen, WJ Lovett-Racke, AE Zhang, GX Rostami, A AF Ding, Xiaoli Yan, Yaping Li, Xing Li, Ke Ciric, Bogoljub Yang, Jingxian Zhang, Yuan Wu, Shuai Xu, Hui Chen, Wanjun Lovett-Racke, Amy E. Zhang, Guang-Xian Rostami, Abdolmohamad TI Silencing IFN-gamma Binding/Signaling in Astrocytes versus Microglia Leads to Opposite Effects on Central Nervous System Autoimmunity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RESPONSES; INTERFERON-GAMMA; MULTIPLE-SCLEROSIS; ENCEPHALOMYELITIS; ACTIVATION; EAE; EXPRESSION; MICE; PATHOGENESIS; INDUCTION AB IFN-gamma, the hallmark cytokine of Th1 cells, plays an important role in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Thus far, the role of IFN-gamma in EAE has been largely studied through its effects on immune cells, whereas much less is known about its effects on CNS cells, especially in vivo. In this study, we dissected the in vivo effects and mechanisms of IFN-gamma binding/signaling in astrocytes and microglia, and found that IFN-gamma signaling in these cell types has opposite effects in EAE pathogenesis. Silencing IFN-gamma binding/signaling in astrocytes alleviated EAE, whereas in microglia, and likely in some infiltrating macrophages, it increased disease severity. Silencing IFN-gamma signaling in astrocytes resulted in diminished expression of chemokines and fewer inflammatory cells infiltrating into the CNS, whereas blocking IFN-gamma binding/signaling in microglia, probably infiltrating macrophages as well, increased disease severity through augmented activation and proliferation of microglia. Further, blocking IFN-gamma binding/signaling in astrocytes alleviated both Th1- and Th17-mediated adoptive EAE, indicating an important role for IFN-gamma signaling in astrocytes in autoimmune CNS inflammation. Thus, our study defines novel mechanisms of action of IFN-gamma in EAE pathogenesis, and also highlights an opportunity for development of multiple sclerosis therapies directed at CNS cells. C1 [Ding, Xiaoli; Yan, Yaping; Li, Xing; Li, Ke; Ciric, Bogoljub; Yang, Jingxian; Zhang, Yuan; Wu, Shuai; Xu, Hui; Zhang, Guang-Xian; Rostami, Abdolmohamad] Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 USA. [Ding, Xiaoli; Yan, Yaping] Shaanxi Normal Univ, Coll Life Sci, Natl Engn Lab Resource Dev Endangered Crude Drugs, Key Lab Minist Educ Med Resources & Nat Pharmaceu, Xian 710062, Peoples R China. [Yang, Jingxian] Liaoning Univ Tradit Chinese Med, Dept Pharmacol, Dalian 110847, Peoples R China. [Chen, Wanjun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. [Lovett-Racke, Amy E.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. RP Rostami, A (reprint author), Thomas Jefferson Univ, Dept Neurol, 900 Walnut St,JHN 300, Philadelphia, PA 19107 USA. EM Guang-Xian.Zhang@jefferson.edu; a.m.rostami@jefferson.edu RI Lovett-Racke, Amy/E-3545-2011 FU National Multiple Sclerosis Society; National Institutes of Health; Groff Foundation; Chinese National Natural Science Foundation [81100888]; Fundamental Research Funds for the Central Universities of China [GK261001027] FX This work was supported by the National Multiple Sclerosis Society, the National Institutes of Health, the Groff Foundation, the Chinese National Natural Science Foundation (Grant 81100888 to X.D. and Y.Y.) and the Fundamental Research Funds for the Central Universities of China (Grant GK261001027 to X.D. and Y.Y.). NR 52 TC 10 Z9 10 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 IS 9 BP 4251 EP 4264 DI 10.4049/jimmunol.1303321 PG 14 WC Immunology SC Immunology GA CH0QN UT WOS:000353727400024 PM 25795755 ER PT J AU Metidji, A Rieder, SA Glass, DD Cremer, I Punkosdy, GA Shevach, EM AF Metidji, Amina Rieder, Sadiye Amcaoglu Glass, Deborah Dacek Cremer, Isabelle Punkosdy, George A. Shevach, Ethan M. TI IFN-alpha/beta Receptor Signaling Promotes Regulatory T Cell Development and Function under Stress Conditions SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PERSISTENT LCMV INFECTION; I INTERFERONS; CLONAL EXPANSION; MEMORY FORMATION; CUTTING EDGE; ACTIVATION; EXPRESSION; DISTINCT; STIMULATION; EFFECTOR AB Type I IFNs are a family of cytokines with antiviral and immunomodulatory properties. Although the antiviral effects of IFNs are well characterized, their immunomodulatory properties are less clear. To specifically address the effects of type I IFNs on T regulatory cells (Tregs), we studied mixed bone marrow chimeras between wild-type and IFN-alpha/beta receptor (IFNAR) knockout (KO) mice, and heterozygous female mice expressing a Treg-specific deletion of the IFNAR. In these two models, IFNAR signaling promotes the development of the Treg lineage in the thymus and their survival in the periphery. IFNAR KO Tregs had a higher expression of the proapoptotic gene Bim and higher frequency of active caspase-positive cells. IFNAR KO Tregs from chimeric mice displayed a more naive phenotype, accompanied by lower levels of CD25 and phosphorylated STAT5. Therefore, in Tregs, IFNAR signaling may directly or indirectly affect phosphorylation of STAT5. In mixed chimeras with Scurfy fetal liver, Tregs derived from IFNAR KO bone marrow were unable to control T effector cell activation and tissue inflammation. Under stress conditions or in a competitive environment, IFNAR signaling may be required to maintain Treg homeostasis and function. C1 [Metidji, Amina; Rieder, Sadiye Amcaoglu; Glass, Deborah Dacek; Punkosdy, George A.; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Metidji, Amina; Cremer, Isabelle] Univ Paris 06, F-75005 Paris, France. [Cremer, Isabelle] INSERM, Ctr Rech Cordeliers, F-75006 Paris, France. [Cremer, Isabelle] Univ Paris 05, F-75006 Paris, France. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N315,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov FU Intramural Program of the National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Program of the National Institute of Allergy and Infectious Diseases. NR 48 TC 9 Z9 10 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 IS 9 BP 4265 EP 4276 DI 10.4049/jimmunol.1500036 PG 12 WC Immunology SC Immunology GA CH0QN UT WOS:000353727400025 PM 25795758 ER PT J AU Ainsua-Enrich, E Serrano-Candelas, E Alvarez-Errico, D Picado, C Sayos, J Rivera, J Martin, M AF Ainsua-Enrich, Erola Serrano-Candelas, Eva Alvarez-Errico, Damiana Picado, Cesar Sayos, Joan Rivera, Juan Martin, Margarita TI The Adaptor 3BP2 Is Required for KIT Receptor Expression and Human Mast Cell Survival SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FC-EPSILON-RI; TRANSCRIPTION FACTOR GATA-3; C-KIT; PROTEIN 3BP2; ANTIGEN RECEPTOR; TYROSINE KINASE; GENE-EXPRESSION; T-CELLS; M-CSF; ACTIVATION AB SH3-binding protein 2 (3BP2) is a cytoplasmic adaptor protein that acts as a positive regulator in mast cell Fc epsilon RI-dependent signaling. The KIT receptor whose ligand is the stem cell factor is necessary for mast cell development, proliferation, and survival as well as for optimal IgE-dependent signal. Activating mutations in KIT have been associated with several diseases including mastocytosis. In the present work, we found that 3BP2 silencing impairs KIT signaling pathways, thus affecting phosphoinositide 3-kinase and MAPK pathways in human mast cells (huMCs) from HMC-1, LAD2 (huMC lines), and CD34(+)-derived mast cells. Unexpectedly, silencing of 3BP2 reduces KIT expression in normal huMCs as well as in HMC-1 cells where KIT is mutated, thus increasing cellular apoptosis and caspase-3/7 activity. 3BP2 silencing reduces KIT transcription expression levels. Interestingly, 3BP2 silencing decreased microphthalmia-associated transcription factor (MITF) expression, a transcription factor involved in KIT expression. Reconstitution of 3BP2 in knockdown cells leads to reversal of KIT expression as well as survival phenotype. Accordingly MITF reconstitution enhances KIT expression levels in 3BP2-silenced cells. Moreover, downregulation of KIT expression by miRNA-221 overexpression or the proteasome inhibitor bortezomib also reduced 3BP2 and MITF expression. Furthermore, KIT tyrosine activity inhibition reduced 3BP2 and MITF expression, demonstrating again a tight and reciprocal relationship between these molecules. Taken together, our results show that 3BP2 regulates huMC survival and participates in KIT-mediated signal transduction by directly controlling KIT receptor expression, suggesting its potential as a therapeutic target in mast cell-mediated inflammatory diseases and deregulated KIT disorders. C1 [Ainsua-Enrich, Erola; Serrano-Candelas, Eva; Alvarez-Errico, Damiana; Martin, Margarita] Univ Barcelona, Fac Med, Biochem Unit, E-08036 Barcelona, Spain. [Ainsua-Enrich, Erola; Serrano-Candelas, Eva; Alvarez-Errico, Damiana; Picado, Cesar; Martin, Margarita] Inst Invest Biomed August Pi & Sunyer, Lab Immunoallergia Resp Clin & Expt, Barcelona 08036, Spain. [Picado, Cesar] Inst Hlth Carlos III, Networking Res Ctr Resp Dis, Madrid 28029, Spain. [Sayos, Joan] Autonomous Univ Barcelona, Mol Biol & Biochem Res Ctr Nanomed, Immunobiol Grp, E-08035 Barcelona, Spain. [Sayos, Joan] Inst Hlth Carlos III, Networking Res Ctr Bioengn Biomat & Nanomed, Madrid 28029, Spain. [Rivera, Juan] NIAMSD, Mol Immunol Sect, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Martin, M (reprint author), Univ Barcelona, Fac Med, Biochem Unit, Carrer Casanova 143, E-08036 Barcelona, Spain. EM martin_andorra@ub.edu RI Sayos, Joan/B-6119-2009; Serrano Candelas, Eva/I-1892-2015; OI Sayos, Joan/0000-0002-4664-3461; Serrano Candelas, Eva/0000-0002-8929-5364; Martin, Margarita/0000-0002-9245-4899 FU Fondo de Investigaciones Sanitarias, Ministerio de Economia y Competitividad (Spain) [PI1200332]; Miguel Servet contract from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III [CP06/00058]; Intramural Research Program within the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health FX This work was supported by Grant PI1200332 from the Fondo de Investigaciones Sanitarias, Ministerio de Economia y Competitividad (Spain). J.S. is supported by a Miguel Servet contract from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (CP06/00058). Work done in J.R.'s laboratory is supported by the Intramural Research Program within the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. NR 59 TC 1 Z9 1 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 IS 9 BP 4309 EP 4318 DI 10.4049/jimmunol.1402887 PG 10 WC Immunology SC Immunology GA CH0QN UT WOS:000353727400029 PM 25810396 ER PT J AU Singh, SP Zhang, HH Tsang, H Gardina, PJ Myers, TG Nagarajan, V Lee, CH Farber, JM AF Singh, Satya P. Zhang, Hongwei H. Tsang, Hsinyi Gardina, Paul J. Myers, Timothy G. Nagarajan, Vijayaraj Lee, Chang Hoon Farber, Joshua M. TI PLZF Regulates CCR6 and Is Critical for the Acquisition and Maintenance of the Th17 Phenotype in Human Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ROR-GAMMA-T; ACUTE PROMYELOCYTIC LEUKEMIA; GENOME-WIDE ASSOCIATION; RHEUMATOID-ARTHRITIS; TRANSCRIPTIONAL REPRESSION; INTERLEUKIN 22; RECEPTOR CCR6; T-H-17 CELLS; RISK LOCI; DIFFERENTIATION AB Th17 cells, which express the chemokine receptor CCR6, are implicated in many immune-mediated disorders, such as psoriasis and multiple sclerosis. We found that expression levels of CCR6 on human effector/memory CD4(+) T cells reflect a continuum of Th17 differentiation. By evaluating the transcriptome in cells with increasing CCR6, we detected progressive upregulation of ZBTB16, which encodes the broad complex, tramtrack, bric-a-brac-zinc finger transcription factor promyelocytic leukemia zinc finger protein (PLZF). Using chromatin immunoprecipitation for modified histones, p300, and PLZF, we identified enhancer-like sites at -9/-10 and -13/-14 kb from the upstream transcription start site of CCR6 that bind PLZF in CCR6(+) cells. For Th cells from adult blood, both in the CCR6(+) memory population and in naive cells activated ex vivo, knockdown of ZBTB16 downregulated CCR6 and other Th17-associated genes. ZBTB16 and RORC (which encodes the "master regulator" RORgt) cross-regulate each other, and PLZF binds at the RORC promoter in CCR6(+) cells. In naive Th cells from cord blood, ZBTB16 expression was confined to CD161(+) cells, which are Th17 cell precursors. ZBTB16 was not expressed in mouse Th17 cells, and Th17 cells could be made from luxoid mice, which harbor an inactivating mutation in Zbtb16. These studies demonstrate a role for PLZF as an activator of transcription important both for Th17 differentiation and the maintenance of the Th17 phenotype in human cells, expand the role of PLZF as a critical regulator in the human adaptive immune system, and identify a novel, essential element in a regulatory network that is of significant therapeutic interest. C1 [Singh, Satya P.; Zhang, Hongwei H.; Tsang, Hsinyi; Lee, Chang Hoon; Farber, Joshua M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Gardina, Paul J.; Myers, Timothy G.] NIAID, Technol Branch, NIH, Bethesda, MD 20892 USA. [Nagarajan, Vijayaraj] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA. RP Farber, JM (reprint author), NIAID, Lab Mol Immunol, NIH, Bldg 10,Room 11N-111,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. EM jfarber@niaid.nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 66 TC 5 Z9 5 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 IS 9 BP 4350 EP 4361 DI 10.4049/jimmunol.1401093 PG 12 WC Immunology SC Immunology GA CH0QN UT WOS:000353727400033 PM 25833398 ER PT J AU Enqvist, M Ask, EH Forslund, E Carlsten, M Abrahamsen, G Beziat, V Andersson, S Schaffer, M Spurkland, A Bryceson, Y Onfelt, B Malmberg, KJ AF Enqvist, Monika Ask, Eivind Heggernes Forslund, Elin Carlsten, Mattias Abrahamsen, Greger Beziat, Vivien Andersson, Sandra A Schaffer, Marie Spurkland, Anne Bryceson, Yenan Onfelt, Bjorn Malmberg, Karl-Johan TI Coordinated Expression of DNAM-1 and LFA-1 in Educated NK Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; MHC CLASS-I; LIPID RAFT RECRUITMENT; INHIBITORY RECEPTORS; CYTOMEGALOVIRUS-INFECTION; ADHESION MOLECULE; FLOW-CYTOMETRY; TARGET-CELLS; SELF-MHC; T-CELL AB The functional capacity of NK cells is dynamically tuned by integrated signals from inhibitory and activating cell surface receptors in a process termed NK cell education. However, the understanding of the cellular and molecular mechanisms behind this functional tuning is limited. In this study, we show that the expression of the adhesion molecule and activation receptor DNAX accessory molecule 1 (DNAM-1) correlates with the quantity and quality of the inhibitory input by HLA class I-specific killer cell Ig-like receptors and CD94/NKG2A as well as with the magnitude of functional responses. Upon target cell recognition, the conformational state of LFA-1 changed in educated NK cells, associated with rapid colocalization of both active LFA-1 and DNAM-1 at the immune synapse. Thus, the coordinated expression of LFA-1 and DNAM-1 is a central component of NK cell education and provides a potential mechanism for controlling cytotoxicity by functionally mature NK cells. C1 [Enqvist, Monika; Carlsten, Mattias; Beziat, Vivien; Andersson, Sandra A; Schaffer, Marie; Bryceson, Yenan; Malmberg, Karl-Johan] Karolinska Inst, Ctr Infect Med, Dept Med, S-14186 Stockholm, Sweden. [Ask, Eivind Heggernes; Malmberg, Karl-Johan] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Canc Immunotherapy, N-0316 Oslo, Norway. [Ask, Eivind Heggernes; Malmberg, Karl-Johan] Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, N-0310 Oslo, Norway. [Forslund, Elin; Onfelt, Bjorn] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden. [Carlsten, Mattias] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Abrahamsen, Greger; Spurkland, Anne] Univ Oslo, Inst Basic Med Sci, N-0317 Oslo, Norway. [Onfelt, Bjorn] Royal Inst Technol, Dept Appl Phys, Sci Life Lab, S-10691 Stockholm, Sweden. RP Malmberg, KJ (reprint author), Karolinska Inst, Ctr Infect Med, F59, S-14186 Stockholm, Sweden. EM kalle.malmberg@ki.se RI Beziat, Vivien/G-2971-2011; OI Beziat, Vivien/0000-0002-4020-824X; Malmberg, Karl-Johan/0000-0002-8718-9373; Spurkland, Anne/0000-0003-4421-0766; Bryceson, Yenan/0000-0002-7783-9934; Carlsten, Mattias/0000-0001-9815-0012 FU Swedish Research Council; Swedish Children's Cancer Society; Swedish Cancer Society; Karolinska Institutet; Wenner-Gren Foundation; Anders Jahres Foundation; Norwegian Cancer Society; Norwegian Research Council; South-Eastern Norway Regional Health Authority; European Research Council; K.G. Jebsen Center for Cancer Immunotherapy FX This work was supported by grants from the Swedish Research Council, the Swedish Children's Cancer Society, the Swedish Cancer Society, the Karolinska Institutet, the Wenner-Gren Foundation, the Anders Jahres Foundation, the Norwegian Cancer Society, the Norwegian Research Council, the South-Eastern Norway Regional Health Authority, the European Research Council, and the K.G. Jebsen Center for Cancer Immunotherapy. NR 50 TC 15 Z9 15 U1 4 U2 13 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 IS 9 BP 4518 EP 4527 DI 10.4049/jimmunol.1401972 PG 10 WC Immunology SC Immunology GA CH0QN UT WOS:000353727400050 PM 25825444 ER PT J AU Zhang, YH Wahl, LM AF Zhang, Yahong Wahl, Larry M. TI Cytokine-induced monocyte MMP-1 is negatively regulated by GSK-3 through a p38 MAPK-mediated decrease in ERK1/2 MAPK activation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE signal transduction; inflammation; connective tissue ID GLYCOGEN-SYNTHASE KINASE-3; MATRIX-METALLOPROTEINASE EXPRESSION; MACROPHAGE COLLAGENASE PRODUCTION; BETA-CATENIN; CANCER-CELLS; DIFFERENTIAL REGULATION; SIGNALING PATHWAY; XENOPUS EMBRYOS; INHIBITION; RECEPTOR AB Elucidation of the signal transduction events leading to the production of MMPs by monocytes/macrophages may provide insights into the mechanisms involved in the destruction of connective tissue associated with chronic inflammatory lesions. Here, we show that GSK-3 is a negative regulator of cytokine-induced MMP-1 production by monocytes. Inhibition of monocyte GSK-3 pharmacologically with SB216763 or GSK-3 beta siRNA caused a significant enhancement of MMP-1 by TNF-alpha- and GM-CSF-activated monocytes, indicating that induction of MMP-1 by TNF-alpha and GM-CSF involved phosphorylation/inactivation of GSK-3. TNF-alpha- and GM-CSF-induced phosphorylation of GSK-3 and subsequent MMP-1 production was blocked with the PKC inhibitor Go6976 but not by the AKT1/2 inhibitor AKT VIII, showing that cytokine phosphorylation of GSK-3 occurs primarily through a PKC pathway. Inhibition of GSK-3 resulted in decreased phosphorylation of p38 MAPK with a corresponding increase in phosphorylation of ERK1/2 MAPK. Enhanced MMP-1 production by treatment with SB216763 was a result of increased ERK1/2 activation, as demonstrated by inhibition of MMP-1 by PD98059, a specific ERK1/2 inhibitor. Conversely, the p38 MAPK inhibitor SB203580 enhanced cytokine activation of ERK1/2 and the production of MMP-1 similar to that of SB216763. These findings demonstrate that the degree of cytokine-mediated phosphorylation/inhibition of GSK-3 determines the level of MMP-1 production through amechanism involving decreased activation of p38 MAPK, a negative regulator of ERK1/2 required for cytokine-induced production of MMP-1 by monocytes. C1 [Zhang, Yahong; Wahl, Larry M.] NIDCR, NIH, Bethesda, MD 20892 USA. RP Wahl, LM (reprint author), NIDCR, NIH, 30 Convent Dr,Bldg 30,Room 109, Bethesda, MD 20892 USA. EM lwahl@mail.nih.gov FU National Institute of Dental and Craniofacial Research U.S. National Institutes of Health FX This study was supported by intramural funds of the National Institute of Dental and Craniofacial Research U.S. National Institutes of Health. NR 49 TC 1 Z9 1 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 EI 1938-3673 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAY PY 2015 VL 97 IS 5 BP 921 EP 927 DI 10.1189/jlb.3A0413-235R PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA CH3BK UT WOS:000353900500010 PM 25714802 ER PT J AU Zheng, B Bernier, M Zhang, XH Suzuki, T Nie, CQ Li, YH Zhang, Y Song, LL Shi, HJ Liu, Y Zheng, CY Wen, JK AF Zheng, Bin Bernier, Michel Zhang, Xin-hua Suzuki, Toru Nie, Chan-quan Li, Yong Hui Zhang, Yong Song, Li-li Shi, Hui-jing Liu, Yan Zheng, Cui-ying Wen, Jin-kun TI miR-200c-SUMOylated KLF4 feedback loop acts as a switch in transcriptional programs that control VSMC proliferation SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Letter DE miR-200c; Ubc9; SUMOylation; KLF4; VSMC; Proliferation ID SMOOTH-MUSCLE-CELLS; MEDIATES NUCLEAR-LOCALIZATION; GENE-EXPRESSION; DOWN-REGULATION; CANCER-CELLS; PROMOTER ACTIVITY; IN-VIVO; SUMOYLATION; GROWTH; ALPHA AB The regulation of vascular smooth muscle cell (VSMC) proliferation is an important issue because it has major implications for the prevention of pathological vascular conditions. Using microRNA array screen, we found the expression levels of 200 unique miRNAs in hyperplasic tissues. Among them, miR-200c expression substantially was down-regulated. The objective of this work was to assess the function of miR-200c and SUMOylated Kruppel-like transcription factor 4 (KLF4) in the regulation of VSMC proliferation in both cultured cells and animal models of balloon injury. Under basal conditions, we found that miR-200c inhibited the expression of KLF4 and the SUMO-conjugating enzyme Ubc9. Upon PDGF-BB treatment, Ubc9 interacted with and promoted the SUMOylation of KLF4, which allowed the recruitment of transcriptional corepressors (e.g., nuclear receptor corepressor (NCoR) and HDAC2) to the miR-200c promoter. The reduction in miR-200c levels led to increased target gene expression (e.g., Ubc9 and KLF4), which further repressed miR-200c levels and accelerated VSMC proliferation. These results demonstrate that induction of a miR-200c-SUMOylated KLF4 feedback loop is a significant aspect of the PDGF-BB proliferative response in VSMCs and that targeting Ubc9 represents a novel approach for the prevention of restenosis. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Zheng, Bin; Zhang, Xin-hua; Nie, Chan-quan; Li, Yong Hui; Song, Li-li; Shi, Hui-jing; Liu, Yan; Zheng, Cui-ying; Wen, Jin-kun] Hebei Med Univ, Dept Biochem & Mol Biol, Shijiazhuang 050017, Peoples R China. [Bernier, Michel] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA. [Suzuki, Toru] Univ Tokyo, Dept Cardiovasc Med, Tokyo, Japan. [Zhang, Yong] Hebei Med Univ, Dept Urinary Surg, Hosp 2, Shijiazhuang 050000, Peoples R China. RP Zheng, B (reprint author), Hebei Med Univ, Dept Biochem & Mol Biol, 361 Zhongshan East Rd, Shijiazhuang 050017, Peoples R China. EM doublezb@sina.com; wjk@hebmu.edu.cn FU Intramural NIH HHS NR 45 TC 8 Z9 8 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 2015 VL 82 BP 201 EP 212 DI 10.1016/j.yjmcc.2015.03.011 PG 12 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA CH6KO UT WOS:000354145700023 PM 25791170 ER PT J AU Sun, N Finkel, T AF Sun, Nuo Finkel, Toren TI Cardiac mitochondria: A surprise about size SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Editorial Material ID ENDOPLASMIC-RETICULUM; HEART-FAILURE; CELL-DEATH; FUSION; DYNAMICS; FISSION; OPA1; FRAGMENTATION; DYSFUNCTION; MORPHOLOGY C1 [Sun, Nuo; Finkel, Toren] NHLBI, Ctr Mol Med, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NIH, Bldg 10-CRC 5-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM finkelt@nih.gov FU Intramural NIH HHS NR 27 TC 1 Z9 1 U1 1 U2 7 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 2015 VL 82 BP 213 EP 215 DI 10.1016/j.yjmcc.2015.01.009 PG 3 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA CH6KO UT WOS:000354145700024 PM 25626176 ER PT J AU Lyoo, CH Ikawa, M Liow, JS Zoghbi, SS Morse, CL Pike, VW Fujita, M Innis, RB Kreisl, WC AF Lyoo, Chul Hyoung Ikawa, Masamichi Liow, Jeih-San Zoghbi, Sami S. Morse, Cheryl L. Pike, Victor W. Fujita, Masahiro Innis, Robert B. Kreisl, William Charles TI Cerebellum Can Serve As a Pseudo-Reference Region in Alzheimer Disease to Detect Neuroinflammation Measured with PET Radioligand Binding to Translocator Protein SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE Alzheimer disease; neuroinflammation; C-11-PBR28; positron emission tomography; ratio method ID PERIPHERAL BENZODIAZEPINE-RECEPTOR; MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; BRAIN; TSPO; POLYMORPHISM AB Alzheimer disease (AD) is associated with an increase in the brain of the 18-kDa translocator protein (TSPO), which is overexpressed in activated microglia and reactive astrocytes. Measuring the density of TSPO with PET typically requires absolute quantitation with arterial blood sampling, because a reference region devoid of TSPO does not exist in the brain. We sought to determine whether a simple ratio method could substitute for absolute quantitation of binding with C-11-PBR28, a second-generation radioligand for TSPO. Methods: C-11-PBR28 PET imaging was performed in 21 healthy controls, 11 individuals with mild cognitive impairment, and 25 AD patients. Group differences in C-11-PBR28 binding were compared using 2 methods. The first was the gold standard method of calculating total distribution volume (VT), using the 2-tissue-compartment model with the arterial input function, corrected for plasma-free fraction of radiotracer (fP). The second method used a ratio of brain uptake in target regions to that in cerebellum-that is, standardized uptake value ratio (SUVR). Results: Using absolute quantitation, we confirmed that TSPO binding (VT/fP) was greater in AD patients than in healthy controls in expected temporoparietal regions and was not significantly different among the 3 groups in the cerebellum. When the cerebellum was used as a pseudo-reference region, the SUVR method detected greater binding in AD patients than controls in the same regions as absolute quantification and in 1 additional region, suggesting SUVR may have greater sensitivity. Coefficients of variation of SUVR measurements were about two-thirds lower than those of absolute quantification, and the resulting statistical significance was much higher for SUVR when comparing AD and healthy controls (e.g., P < 0.0005 for SUVR vs. P = 0.023 for V-T/fP in combined middle and inferior temporal cortex). Conclusion: To measure TSPO density in AD patients and control subjects, a simple ratio method SUVR can substitute for, and may even be more sensitive than, absolute quantitation. The SUVR method is expected to improve subject tolerability by allowing shorter scanning time and not requiring arterial catheterization. In addition, this ratio method allows smaller sample sizes for comparable statistical significance because of the relatively low variability of the ratio values. C1 [Lyoo, Chul Hyoung] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Nephrol, Seoul 120749, South Korea. [Lyoo, Chul Hyoung; Ikawa, Masamichi; Liow, Jeih-San; Zoghbi, Sami S.; Morse, Cheryl L.; Pike, Victor W.; Fujita, Masahiro; Innis, Robert B.; Kreisl, William Charles] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Kreisl, William Charles] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA. RP Kreisl, WC (reprint author), Taub Inst, Dept Neurol, 622 W 168th St,PH 19th Floor, New York, NY 10032 USA. EM kreislw@mail.nih.gov FU Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH); American Academy of Neurology Foundation [NCT00613119, 08-M-0066] FX The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734. This project was funded in part by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH), and a fellowship award from the American Academy of Neurology Foundation, under clinicaltrials.gov identifier NCT00613119 (protocol # 08-M-0066). No other potential conflict of interest relevant to this article was reported. NR 25 TC 23 Z9 23 U1 0 U2 5 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 IS 5 BP 701 EP 706 DI 10.2967/jnumed.114.146027 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CH2CB UT WOS:000353831000015 PM 25766898 ER PT J AU Grady, PA Rosenbaum, LM AF Grady, Patricia A. Rosenbaum, Louise M. TI The Science of Caregiver Health SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Editorial Material ID INTERVENTIONS; METAANALYSIS C1 [Grady, Patricia A.; Rosenbaum, Louise M.] NINR, NIH, Bethesda, MD 20892 USA. RP Grady, PA (reprint author), NINR, NIH, Bethesda, MD 20892 USA. EM rosenbauml@mail.nih.gov FU Intramural NIH HHS [Z99 NR999999] NR 6 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6546 EI 1547-5069 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PD MAY PY 2015 VL 47 IS 3 BP 197 EP 199 DI 10.1111/jnu.12137 PG 3 WC Nursing SC Nursing GA CH4ER UT WOS:000353986300002 PM 25809219 ER PT J AU Jenkins, J Calzone, KA Caskey, S Culp, S Weiner, M Badzek, L AF Jenkins, Jean Calzone, Kathleen A. Caskey, Sarah Culp, Stacey Weiner, Marsha Badzek, Laurie TI Methods of Genomic Competency Integration in Practice SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE Champions; competency; education; genomics; nursing ID NURSING PRACTICE AB PurposeGenomics is increasingly relevant to health care, necessitating support for nurses to incorporate genomic competencies into practice. The primary aim of this project was to develop, implement, and evaluate a year-long genomic education intervention that trained, supported, and supervised institutional administrator and educator champion dyads to increase nursing capacity to integrate genomics through assessments of program satisfaction and institutional achieved outcomes. DesignLongitudinal study of 23 Magnet Recognition Program (R) Hospitals (21 intervention, 2 controls) participating in a 1-year new competency integration effort aimed at increasing genomic nursing competency and overcoming barriers to genomics integration in practice. MethodsChampion dyads underwent genomic training consisting of one in-person kick-off training meeting followed by monthly education webinars. Champion dyads designed institution-specific action plans detailing objectives, methods or strategies used to engage and educate nursing staff, timeline for implementation, and outcomes achieved. Action plans focused on a minimum of seven genomic priority areas: champion dyad personal development; practice assessment; policy content assessment; staff knowledge needs assessment; staff development; plans for integration; and anticipated obstacles and challenges. Action plans were updated quarterly, outlining progress made as well as inclusion of new methods or strategies. Progress was validated through virtual site visits with the champion dyads and chief nursing officers. Descriptive data were collected on all strategies or methods utilized, and timeline for achievement. Descriptive data were analyzed using content analysis. FindingsThe complexity of the competency content and the uniqueness of social systems and infrastructure resulted in a significant variation of champion dyad interventions. ConclusionsNursing champions can facilitate change in genomic nursing capacity through varied strategies but require substantial training in order to design and implement interventions. Clinical RelevanceGenomics is critical to the practice of all nurses. There is a great opportunity and interest to address genomic knowledge deficits in the practicing nurse workforce as a strategy to improve patient outcomes. Exemplars of champion dyad interventions designed to increase nursing capacity focus on improving education, policy, and healthcare services. C1 [Jenkins, Jean] NHGRI, Genom Healthcare Branch, Div Policy Commun & Educ, NIH, Bethesda, MD 20892 USA. [Calzone, Kathleen A.] NCI, Res, NIH, Ctr Canc Res,Genet Branch, Bethesda, MD 20892 USA. [Caskey, Sarah; Culp, Stacey; Badzek, Laurie] W Virginia Univ, Sch Nursing, Morgantown, WV 26506 USA. [Weiner, Marsha] Keiser Univ, Sarasota, FL USA. RP Jenkins, J (reprint author), NHGRI, Genom Healthcare Branch, Div Policy Commun & Educ, NIH, Bldg 31 Rm 4B09, Bethesda, MD 20892 USA. EM jean.jenkins@nih.gov FU National Council of State Boards of Nursing; West Virginia University; Intramural Research Program of the National Institutes of Health, National Cancer Institute; National Human Genome Research Institute, Division of Policy, Communications, and Education FX This research was funded through a grant from the National Council of State Boards of Nursing, and supported by West Virginia University and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and National Human Genome Research Institute, Division of Policy, Communications, and Education. NR 15 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6546 EI 1547-5069 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PD MAY PY 2015 VL 47 IS 3 BP 200 EP 210 DI 10.1111/jnu.12131 PG 11 WC Nursing SC Nursing GA CH4ER UT WOS:000353986300003 PM 25808828 ER PT J AU Kirrane, EF Bowman, C Davis, JA Hoppin, JA Blair, A Chen, HL Patel, MM Sandler, DP Tanner, CM Vinikoor-Imler, L Ward, MH Luben, TJ Kamel, F AF Kirrane, Ellen F. Bowman, Christal Davis, J. Allen Hoppin, Jane A. Blair, Aaron Chen, Honglei Patel, Molini M. Sandler, Dale P. Tanner, Caroline M. Vinikoor-Imler, Lisa Ward, Mary H. Luben, Thomas J. Kamel, Freya TI Associations of Ozone and PM2.5 Concentrations With Parkinson's Disease Among Participants in the Agricultural Health Study SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID FINE PARTICULATE MATTER; LONG-TERM EXPOSURE; AIR-POLLUTION; COGNITIVE FUNCTION; CARDIOVASCULAR MORTALITY; OXIDATIVE STRESS; OLDER-ADULTS; US ADULTS; BRAIN; COHORT AB Objective: This study describes associations of ozone and fine particulate matter with Parkinson's disease observed among farmers in North Carolina and Iowa. Methods: We used logistic regression to determine the associations of these pollutants with self-reported, doctor-diagnosed Parkinson's disease. Daily predicted pollutant concentrations were used to derive surrogates of long-term exposure and link them to study participants' geocoded addresses. Results: We observed positive associations of Parkinson's disease with ozone (odds ratio = 1.39; 95% CI: 0.98 to 1.98) and fine particulate matter (odds ratio = 1.34; 95% CI: 0.93 to 1.93) in North Carolina but not in Iowa. Conclusions: The plausibility of an effect of ambient concentrations of these pollutants on Parkinson's disease risk is supported by experimental data demonstrating damage to dopaminergic neurons at relevant concentrations. Additional studies are needed to address uncertainties related to confounding and to examine temporal aspects of the associations we observed. C1 [Kirrane, Ellen F.; Bowman, Christal; Davis, J. Allen; Patel, Molini M.; Vinikoor-Imler, Lisa; Luben, Thomas J.] US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Res Triangle Pk, NC 27709 USA. [Hoppin, Jane A.; Chen, Honglei; Sandler, Dale P.; Kamel, Freya] NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Blair, Aaron; Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD USA. [Tanner, Caroline M.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. [Tanner, Caroline M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Kirrane, EF (reprint author), US EPA, Natl Ctr Environm Assessment, Off Res & Dev, 109 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM kirrane.ellen@epa.gov OI Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018; Chen, Honglei/0000-0003-3446-7779 FU intramural research program of the National Institutes of Health; National Institute of Environmental Health Sciences [Z01-ES049030]; National Cancer Institute [Z01-CP010119] FX This work was supported in part by the intramural research program of the National Institutes of Health, the National Institute of Environmental Health Sciences (Z01-ES049030), and National Cancer Institute (Z01-CP010119). Data were obtained from Agricultural Health Study data release versions P1REL0906.00 (for phase 1), P2REL0907.00 (phase 2), and P3RREL0901 (phase 3). The views expressed in this article are those of the authors and do not necessarily represent the views or policies of the US Environmental Protection Agency. Dr Caroline Tanner has served as a consultant to Pfizer Pharmaceuticals, a manufacturer of treatments for Parkinson's disease. No other potential conflicts of interest were declared. NR 46 TC 5 Z9 5 U1 3 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAY PY 2015 VL 57 IS 5 BP 509 EP 517 DI 10.1097/JOM.0000000000000451 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CH7NY UT WOS:000354225000006 PM 25951420 ER PT J AU Bunt, CW Burke, HB Towbin, AJ Hoang, A Stephens, MB Fontelo, P Liu, F Gimbel, RW AF Bunt, Christopher W. Burke, Harry B. Towbin, Alexander J. Hoang, Albert Stephens, Mark B. Fontelo, Paul Liu, Fang Gimbel, Ronald W. TI Point-of-Care Estimated Radiation Exposure and Imaging Guidelines Can Reduce Pediatric Radiation Burden SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article DE Clinical Decision Support Systems; Decision Making; Evidence-Based Medicine; Radiation; Radiology ID CT AB Introduction: The steady increase in the use of computed tomography (CT) has particular concerns for children. Family physicians must often select pediatric imaging without any decision support. We hypothesized that point-of-care decision support would lead to the selection of imaging that lowered radiation exposure and improved guideline congruence. Methods: Our double-blind, randomized simulation included family physicians in the Military Health System. Participants initially reviewed a pediatric hematuria scenario and selected imaging without decision support. Participants were subsequently randomized to either receive imaging-appropriateness guidelines and then estimated radiation exposure information or receive estimated radiation information then guidelines; imaging selections were required after each step. The primary outcome was the selected imaging modality with point-of-care decision support. Results: The first arm increased CT ordering after viewing the guidelines (P = .008) but then decreased it after reviewing radiation exposure information (P = .007). In the second arm radiation information decreased CT and plain film use (P = not significant), with a subsequent increase in ultrasound and CT after the guideline presentation (P = .05). Conclusions: Decision support during a simulated pediatric scenario helped family physicians select imaging that lowered radiation exposure and was aligned with current guidelines, especially when presented with radiation information after guideline review. This information could help inform electronic medical record design. C1 [Bunt, Christopher W.; Stephens, Mark B.] Uniformed Serv Univ Hlth Sci, Dept Family Med, Bethesda, MD 20814 USA. [Burke, Harry B.; Hoang, Albert] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. [Towbin, Alexander J.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat Radiol, Cincinnati, OH 45229 USA. [Fontelo, Paul; Liu, Fang] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. [Gimbel, Ronald W.] Clemson Univ, Dept Publ Hlth Sci, Clemson, SC USA. RP Bunt, CW (reprint author), Uniformed Serv Univ Hlth Sci, Dept Family Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM christopher.bunt@usuhs.edu OI Bunt, Christopher/0000-0002-5130-6902; Towbin, Alexander/0000-0003-1729-5071 FU Uniformed Services University [R02930.4]; US Department of Defense Patient Safety Program FX Intramural funding was provided by the Uniformed Services University (grant no. R02930.4) and the US Department of Defense Patient Safety Program. NR 11 TC 1 Z9 1 U1 0 U2 1 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 EI 1558-7118 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD MAY-JUN PY 2015 VL 28 IS 3 BP 343 EP 350 DI 10.3122/jabfm.2015.03.140251 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA CH8HR UT WOS:000354277700009 PM 25957367 ER PT J AU Recuenco, MC Ohmori, T Tanigawa, S Taguchi, A Fujimura, S Conti, MA Wei, QZ Kiyonari, H Abe, T Adelstein, RS Nishinakamura, R AF Recuenco, Mariam C. Ohmori, Tomoko Tanigawa, Shunsuke Taguchi, Atsuhiro Fujimura, Sayoko Conti, Mary Anne Wei, Qize Kiyonari, Hiroshi Abe, Takaya Adelstein, Robert S. Nishinakamura, Ryuichi TI Nonmuscle Myosin II Regulates the Morphogenesis of Metanephric Mesenchyme-Derived Immature Nephrons SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID KIDNEY DEVELOPMENT; AFRICAN-AMERICANS; HEAVY-CHAIN; MURINE HOMOLOG; RENAL-DISEASE; MYH9; GENE; CELLS; PROLIFERATION; EXPRESSION AB The kidney develops from reciprocal interactions between the metanephric mesenchyme and ureteric bud. The mesenchyme transforms into epithelia and forms complicated nephron structures, whereas the ureteric bud extends its pre-existing epithelial ducts. Although the roles are well established for extracellular stimuli, such as Wnt and Notch, it is unclear how the intracellular cytoskeleton regulates these morphogenetic processes. Myh9 and Myh10 encode nonmuscle myosin II heavy chains, and Myh9 mutations in humans are implicated in congenital kidney diseases and focal segmental glomerulosclerosis in adults. Here, we analyzed the roles of Myh9 and Myh10 in the developing kidney. Ureteric bud-specific depletion of Myh9 resulted in no apparent phenotypes, whereas mesenchyme-specific Myh9 deletion caused proximal tubule dilations and renal failure. Mesenchyme-specific Myh9/Myh10 mutant mice died shortly after birth and showed a severe defect in nephron formation. The nascent mutant nephrons failed to form a continuous lumen, which likely resulted from impaired apical constriction of the elongating tubules. In addition, nephron progenitors lacking Myh9/Myh10 or the possible interactor Kif26b were less condensed at midgestation and reduced at birth. Taken together, nonmuscle myosin II regulates the morphogenesis of immature nephrons derived from the metanephric mesenchyme and the maintenance of nephron progenitors. Our data also suggest that Myh9 deletion in mice results in failure to maintain renal tubules but not in glomerulosclerosis. C1 [Recuenco, Mariam C.; Ohmori, Tomoko; Tanigawa, Shunsuke; Taguchi, Atsuhiro; Nishinakamura, Ryuichi] Kumamoto Univ, Dept Kidney Dev, Kumamoto 8600811, Japan. [Fujimura, Sayoko] Kumamoto Univ, Inst Mol Embryol & Genet, Liaison Lab Res Promot Ctr, Kumamoto 8600811, Japan. [Conti, Mary Anne; Wei, Qize; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. [Kiyonari, Hiroshi; Abe, Takaya] RIKEN Ctr Dev Biol, Lab Anim Resources & Genet Engn, Kobe, Hyogo, Japan. RP Nishinakamura, R (reprint author), Kumamoto Univ, Inst Mol Embryol & Genet, Dept Kidney Dev, 2-2-1 Honjo, Kumamoto 8600811, Japan. EM ryuichi@kumamoto-u.ac.jp RI Kiyonari, Hiroshi/N-7936-2015; OI Taguchi, Atsuhiro/0000-0003-1741-2987; Adelstein, Robert/0000-0002-8683-2144 FU KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology, Japan [24112518, 24790851] FX This study was supported by KAKENHI Grants 24112518 and 24790851 from the Ministry of Education, Culture, Sports, Science and Technology, Japan. NR 33 TC 3 Z9 3 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2015 VL 26 IS 5 BP 1081 EP 1091 DI 10.1681/ASN.2014030281 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA CH2PX UT WOS:000353868200012 PM 25168025 ER PT J AU Woodard, T Sigurdsson, S Gotal, JD Torjesen, AA Inker, LA Aspelund, T Eiriksdottir, G Gudnason, V Harris, TB Launer, LJ Levey, AS Mitchell, GF AF Woodard, Todd Sigurdsson, Sigurdur Gotal, John D. Torjesen, Alyssa A. Inker, Lesley A. Aspelund, Thor Eiriksdottir, Gudny Gudnason, Vilmundur Harris, Tamara B. Launer, Lenore J. Levey, Andrew S. Mitchell, Gary F. TI Mediation Analysis of Aortic Stiffness and Renal Microvascular Function SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; PULSE-WAVE VELOCITY; GLOMERULAR-FILTRATION-RATE; ARTERIAL STIFFNESS; GENE/ENVIRONMENT SUSCEPTIBILITY; MORTALITY; PULSATILITY; REYKJAVIK; PRESSURE; SURVIVAL AB Aortic stiffening, assessed by carotid-femoral pulse wave velocity, is associated with CKD. Transmission of excessive flow pulsatility into the low-impedance renal microvasculature may mediate this association. However, direct analyses of macrovascular-microvascular relations in the kidney are limited. Using arterial tonometry, iohexol clearance, and magnetic resonance imaging, we related arterial stiffness, GFR, urinary albumin excretion, and potential mediators, including renal artery pulsatility index, renal vascular resistance, and arterial volume in the cortex, in 367 older adults (ages 72-92 years) participating in the Age, Gene/Environment Susceptibility-Reykjavik Study. In a model adjusted for age, sex, heart rate, and body size, aortic stiffness was related to GFR (Slope of regression B=-2.28 +/- 0.85 ml/min per SD, P=0.008) but not urine albumin (P=0.09). After accounting for pulsatility index, the relation between aortic stiffness and GFR was no longer significant (P=0.10). Mediation analysis showed that 34% of the relation between aortic stiffness and GFR was mediated by pulsatility index (95% confidence interval of indirect effect, -1.35 to -0.29). An additional 20% or 36% of the relation was mediated by lower arterial volume in the cortex or higher renal vascular resistance, respectively, when offered as mediators downstream from higher pulsatility index (95% confidence interval of indirect effect including arterial volume in the cortex, -2.22 to -0.40; 95% confidence interval of indirect effect including renal vascular resistance, -2.51 to -0.76). These analyses provide the first evidence that aortic stiffness may contribute to lower GFR by transferring excessive flow pulsatility into the susceptible renal microvasculature, leading to dynamic constriction or vessel loss. C1 [Woodard, Todd; Gotal, John D.; Torjesen, Alyssa A.; Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA 02062 USA. [Sigurdsson, Sigurdur; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Inker, Lesley A.; Levey, Andrew S.] Tufts Med Ctr, Dept Med, William B Schwartz Div Nephrol, Boston, MA USA. [Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Harris, Tamara B.; Launer, Lenore J.] NIA, NIH, Bethesda, MD 20892 USA. RP Mitchell, GF (reprint author), Cardiovasc Engn Inc, 1 Edgewater Dr,Suite 201A, Norwood, MA 02062 USA. EM GaryFMitchell@mindspring.com RI Gudnason, Vilmundur/K-6885-2015; Aspelund, Thor/C-5983-2008 OI Gudnason, Vilmundur/0000-0001-5696-0084; Aspelund, Thor/0000-0002-7998-5433 FU National Institutes of Health [N01-AG-12100]; National Institute on Aging Intramural Research Program; Althingi (the Icelandic Parliament); National Institutes of Health National Heart, Lung and Blood Institute [HL094898]; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [DK082447]; Hjartavernd (the Icelandic Heart Association) FX This work was supported by National Institutes of Health Grant N01-AG-12100, the National Institute on Aging Intramural Research Program, Hjartavernd (the Icelandic Heart Association), the Althingi (the Icelandic Parliament), National Institutes of Health National Heart, Lung and Blood Institute Grant HL094898, and National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases Grant DK082447. NR 29 TC 16 Z9 17 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2015 VL 26 IS 5 BP 1181 EP 1187 DI 10.1681/ASN.2014050450 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CH2PX UT WOS:000353868200021 PM 25294231 ER PT J AU Badirou, I Pan, J Souquere, S Legrand, C Pierron, G Wang, A Eckly, A Roy, A Gachet, C Vainchenker, W Chang, Y Leon, C AF Badirou, I. Pan, J. Souquere, S. Legrand, C. Pierron, G. Wang, A. Eckly, A. Roy, A. Gachet, C. Vainchenker, W. Chang, Y. Leon, C. TI Distinct localizations and roles of non-muscle myosin II during proplatelet formation and platelet release SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE megakaryocyte; Non-muscle myosin type IIA; Non-muscle myosin type IIB; platelet; stem cell ID RESTRICTED MYH9 INACTIVATION; CONTRACTILE RING; ISOFORM; MICE; POLYPLOIDIZATION; INHIBITION; EXPRESSION; DEFECTS; RUNX1; TAIL AB BackgroundAt the end of maturation, megakaryocytes (MKs) form long cytoplasmic extensions called proplatelets (PPT). Enormous changes in cytoskeletal structures cause PPT to extend further, to re-localize organelles such as mitochondria and to fragment, leading to platelet release. Two non-muscle myosin IIs (NMIIs) are expressed in MKs; however, only NMII-A (MYH9), but not NMII-B (MYH10), is expressed in mature MKs and is implicated in PPT formation. ObjectivesTo provide invivo evidence on the specific role of NMII-A and IIB in MK PPT formation. MethodsWe studied two transgenic mouse models in which non-muscle myosin heavy chain (NMHC) II-A was genetically replaced either by II-B or by a chimeric NMHCII that combined the head domain of II-A with the rod and tail domains of II-B. Results and ConclusionsThis work demonstrates that the kinetic properties of NM-IIA, depending on the N-terminal domain, render NMII-A the better NMII candidate to control PPT formation. Furthermore, the carboxyl-terminal domain determines myosin II localization in the constriction region of PPT and is responsible for the specific role of NMII in platelet release. C1 [Badirou, I.; Pan, J.; Legrand, C.; Eckly, A.; Roy, A.; Gachet, C.; Vainchenker, W.; Chang, Y.; Leon, C.] INSERM, Villejuif, France. [Badirou, I.; Pan, J.; Souquere, S.; Legrand, C.; Pierron, G.; Roy, A.; Vainchenker, W.; Chang, Y.] Univ Paris Sud, F-94275 Le Kremlin Bicetre, France. [Badirou, I.; Pan, J.; Souquere, S.; Legrand, C.; Pierron, G.; Roy, A.; Vainchenker, W.; Chang, Y.] Inst Gustave Roussy, Villejuif, France. [Souquere, S.; Pierron, G.] CNRS, Villejuif, France. [Wang, A.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. [Eckly, A.; Gachet, C.; Leon, C.] Etab Francais Sang Alsace, Strasbourg, France. [Eckly, A.; Gachet, C.; Leon, C.] Univ Strasbourg, Fac Med, Strasbourg, France. [Eckly, A.; Gachet, C.; Leon, C.] Federat Med Translat, Strasbourg, France. RP Chang, Y (reprint author), INSERM, U1009, Villejuif, France. EM yunhua.chang-marchand@inserm.fr RI leon, catherine/G-6473-2015; Gachet, Christian/H-9156-2016 OI leon, catherine/0000-0002-8597-9929; FU INSERM; Agence Nationale de la Recherche (ANR Jeune chercheur); la Ligue Nationale Contre le Cancer; ANR; China Scholarship Council; la Societe Francaise d'Hematologie; la Fondation de la Recherche Medicale (FRM) FX This work was supported by INSERM, by the Agence Nationale de la Recherche (ANR Jeune chercheur) (Y. Chang), and by grants from la Ligue Nationale Contre le Cancer (Equipe labellisee 2012). I. Badirou was supported by the ANR, and J. Pan by the China Scholarship Council and la Societe Francaise d'Hematologie. A. Roy is supported by a grant from la Fondation de la Recherche Medicale (FRM). We thank L. Lodier, J. Weber and P. Laeuffer for their technical help. NR 19 TC 1 Z9 2 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD MAY PY 2015 VL 13 IS 5 BP 851 EP 859 DI 10.1111/jth.12887 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CH8AU UT WOS:000354259000021 PM 25736522 ER PT J AU Dimichele, DM Lacroix-Desmazes, S Peyvandi, F Srivastava, A Rosendaal, FR AF Dimichele, D. M. Lacroix-Desmazes, S. Peyvandi, F. Srivastava, A. Rosendaal, F. R. CA Subcomm Factor VIII Factor IX Rare TI Design of clinical trials for new products in hemophilia: communication from the SSC of the ISTH SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article ID FACTOR-VIII PRODUCTS; INHIBITOR DEVELOPMENT; EUROPEAN GUIDELINES; EVOLUTION; CHILDREN C1 [Dimichele, D. M.] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. [Lacroix-Desmazes, S.] Univ Paris 05, Univ Paris 06, Ctr Rech Cordeliers, INSERM,UMR S 1138, Paris, France. [Peyvandi, F.] Univ Milan, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Fdn Luigi Villa, Milan, Italy. [Peyvandi, F.] Univ Milan, Dept Pathophysiol & Transplantat, Milan, Italy. [Srivastava, A.] Christian Med Coll & Hosp, Dept Hematol, Vellore, Tamil Nadu, India. [Rosendaal, F. R.] Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands. [Rosendaal, F. R.] Leiden Univ, Dept Thrombosis & Haemostasis, Med Ctr, Leiden, Netherlands. RP Dimichele, DM (reprint author), NHLBI, Div Blood Dis & Resources, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM donna.dimichele@nih.gov OI Peyvandi, Flora/0000-0001-7423-9864 FU Novo Nordisk; Biotest; Kedrion Biopharma; CSL Behring; LFB; Grifols; Bayer; Baxter; Biokit; Alnylam; Octapharma FX F. Peyvandi reports grants and personal fees from Novo Nordisk, Biotest, and Kedrion Biopharma and personal fees from CSL Behring, LFB, Grifols, Bayer, Baxter, Biokit, Alnylam and Octapharma outside the submitted work. All other authors state that they have no conflict of interest. NR 14 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD MAY PY 2015 VL 13 IS 5 BP 876 EP 879 DI 10.1111/jth.12882 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CH8AU UT WOS:000354259000024 PM 25728341 ER PT J AU Kusek, JW AF Kusek, John W. TI Is it time to tip your glass to prevent CKD? SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID CHRONIC KIDNEY-DISEASE; ALCOHOL-CONSUMPTION; FUNCTION DECLINE; FOLLOW-UP; RISK; POPULATION; MEN AB Chronic kidney disease (CKD) is a major global medical and public health challenge. On the basis primarily of a modest number of prospective epidemiological studies, it appears that alcohol consumption reduces the risk of CKD in the general population. Our understanding of the potential benefits of alcohol consumption with regard to CKD is likely to evolve in the future and will be informed primarily by observational epidemiological studies. C1 NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Kusek, JW (reprint author), NIDDK, Div Kidney Urol & Hematol Dis, NIH, Room 617,6707 Democracy Blvd,Two Democracy Plaza, Bethesda, MD 20892 USA. EM kusekj@extra.niddk.nih.gov FU Intramural NIH HHS [Z99 DK999999] NR 9 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2015 VL 87 IS 5 BP 877 EP 879 DI 10.1038/ki.2015.54 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA CH5HS UT WOS:000354066900003 PM 25951066 ER PT J AU Gorski, M Tin, A Garnaas, M McMahon, GM Chu, AY Tayo, BO Pattaro, C Teumer, A Chasman, DI Chalmers, J Hamet, P Tremblay, J Woodward, M Aspelund, T Eiriksdottir, G Gudnason, V Harris, TB Launer, LJ Smith, AV Mitchell, BD O'Connell, JR Shuldiner, AR Coresh, J Li, M Freudenberger, P Hofer, E Schmidt, H Schmidt, R Holliday, EG Mitchell, P Wang, JJ de Boer, IH Li, G Siscovick, DS Kutalik, Z Corre, T Vollenweider, P Waeber, G Gupta, J Kanetsky, PA Hwang, SJ Olden, M Yang, Q de Andrade, M Atkinson, EJ Kardia, SLR Turner, ST Stafford, JM Ding, JZ Liu, YM Barlassina, C Cusi, D Salvi, E Staessen, JA Ridker, PM Grallert, H Meisinger, C Muller-Nurasyid, M Kramer, BK Kramer, H Rosas, SE Nolte, IM Penninx, BW Snieder, H Del Greco, MF Franke, A Nothlings, U Lieb, W Bakker, SJL Gansevoort, RT van der Harst, P Dehghan, A Franco, OH Hofman, A Rivadeneira, F Sedaghat, S Uitterlinden, AG Coassin, S Haun, M Kollerits, B Kronenberg, F Paulweber, B Aumann, N Endlich, K Pietzner, M Volker, U Rettig, R Chouraki, V Helmer, C Lambert, JC Metzger, M Stengel, B Lehtimaki, T Lyytikainen, LP Raitakari, O Johnson, A Parsa, A Bochud, M Heid, IM Goessling, W Kottgen, A Kao, WHL Fox, CS Boger, CA AF Gorski, Mathias Tin, Adrienne Garnaas, Maija McMahon, Gearoid M. Chu, Audrey Y. Tayo, Bamidele O. Pattaro, Cristian Teumer, Alexander Chasman, Daniel I. Chalmers, John Hamet, Pavel Tremblay, Johanne Woodward, Marc Aspelund, Thor Eiriksdottir, Gudny Gudnason, Vilmundur Harris, Tamara B. Launer, Lenore J. Smith, Albert V. Mitchell, Braxton D. O'Connell, Jeffrey R. Shuldiner, Alan R. Coresh, Josef Li, Man Freudenberger, Paul Hofer, Edith Schmidt, Helena Schmidt, Reinhold Holliday, Elizabeth G. Mitchell, Paul Wang, Jie Jin de Boer, Ian H. Li, Guo Siscovick, David S. Kutalik, Zoltan Corre, Tanguy Vollenweider, Peter Waeber, Gerard Gupta, Jayanta Kanetsky, Peter A. Hwang, Shih-Jen Olden, Matthias Yang, Qiong de Andrade, Mariza Atkinson, Elizabeth J. Kardia, Sharon L. R. Turner, Stephen T. Stafford, Jeanette M. Ding, Jingzhong Liu, Yongmei Barlassina, Cristina Cusi, Daniele Salvi, Erika Staessen, Jan A. Ridker, Paul M. Grallert, Harald Meisinger, Christa Mueller-Nurasyid, Martina Kraemer, Bernhard K. Kramer, Holly Rosas, Sylvia E. Nolte, Ilja M. Penninx, Brenda W. Snieder, Harold Del Greco, M. Fabiola Franke, Andre Noethlings, Ute Lieb, Wolfgang Bakker, Stephan J. L. Gansevoort, Ron T. van der Harst, Pim Dehghan, Abbas Franco, Oscar H. Hofman, Albert Rivadeneira, Fernando Sedaghat, Sanaz Uitterlinden, Andre G. Coassin, Stefan Haun, Margot Kollerits, Barbara Kronenberg, Florian Paulweber, Bernhard Aumann, Nicole Endlich, Karlhans Pietzner, Mike Voelker, Uwe Rettig, Rainer Chouraki, Vincent Helmer, Catherine Lambert, Jean-Charles Metzger, Marie Stengel, Benedicte Lehtimaki, Terho Lyytikainen, Leo-Pekka Raitakari, Olli Johnson, Andrew Parsa, Afshin Bochud, Murielle Heid, Iris M. Goessling, Wolfram Kottgen, Anna Kao, W. H. Linda Fox, Caroline S. Boeger, Carsten A. TI Genome-wide association study of kidney function decline in individuals of European descent SO KIDNEY INTERNATIONAL LA English DT Article DE chronic kidney disease; genome-wide association study; kidney function decline; kidney development; population genetics; single nucleotide polymorphism; zebrafish ID GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; SYNDROME TYPE 1D; HYPERTENSIVE NEPHROSCLEROSIS; DIABETIC-NEPHROPATHY; DEAFNESS DFNB12; MORTALITY RISK; MOUSE MODEL; GENE; PROGRESSION AB Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline. C1 [Gorski, Mathias; Olden, Matthias; Heid, Iris M.] Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany. [Gorski, Mathias; Boeger, Carsten A.] Univ Hosp Regensburg, Dept Nephrol, D-93042 Regensburg, Germany. [Tin, Adrienne; Coresh, Josef; Li, Man; Kottgen, Anna; Kao, W. H. Linda] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Garnaas, Maija] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA. [McMahon, Gearoid M.] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA. [McMahon, Gearoid M.] Harvard Univ, Sch Med, Boston, MA USA. [McMahon, Gearoid M.; Hwang, Shih-Jen; Olden, Matthias; Yang, Qiong; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Chu, Audrey Y.; Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Tayo, Bamidele O.; Kramer, Holly] Loyola Univ Chicago, Loyola Med Ctr, Dept Publ Hlth Serv, Maywood, IL USA. [Pattaro, Cristian; Del Greco, M. Fabiola] Univ Lubeck, European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy. [Teumer, Alexander; Voelker, Uwe] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, Greifswald, Germany. [Chalmers, John; Woodward, Marc] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia. [Hamet, Pavel] Univ Montreal, Ctr Hosp, Ctr Rech, Montreal, PQ, Canada. [Tremblay, Johanne] CHUM Res Center, Montreal, PQ, Canada. [Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur; Smith, Albert V.] Icelandic Heart Assoc, Res Inst, Kopavogur, Iceland. [Aspelund, Thor; Gudnason, Vilmundur; Smith, Albert V.] Univ Iceland, Reykjavik, Iceland. [Harris, Tamara B.; Launer, Lenore J.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Mitchell, Braxton D.; O'Connell, Jeffrey R.; Shuldiner, Alan R.; Parsa, Afshin] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Mitchell, Braxton D.; O'Connell, Jeffrey R.; Shuldiner, Alan R.; Parsa, Afshin] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA. [Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21201 USA. [Coresh, Josef; Kao, W. H. Linda] Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Freudenberger, Paul; Schmidt, Helena] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria. [Hofer, Edith] Med Univ Graz, Inst Med Informat Stat & Documentat, Dept Neurol, Graz, Austria. [Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Graz, Austria. [Holliday, Elizabeth G.] Univ Newcastle, CReDITSS, HMRI, Ctr Clin Epidemiol & Biostat, Callaghan, NSW 2308, Australia. [Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Westmead Hosp, Westmead Millennium Inst, Ctr Vis Res, Sydney, NSW 2006, Australia. [de Boer, Ian H.] Univ Washington, Seattle, WA 98195 USA. [Li, Guo; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Siscovick, David S.] New York Acad Med, New York, NY USA. [Kutalik, Zoltan; Corre, Tanguy] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. [Kutalik, Zoltan] Swiss Inst Bioinformat, Dept Med Genet, Lausanne, Switzerland. [Vollenweider, Peter; Waeber, Gerard] Univ Lausanne Hosp, Dept Internal Med, Lausanne, Switzerland. [Gupta, Jayanta; Kanetsky, Peter A.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [de Andrade, Mariza; Atkinson, Elizabeth J.; Turner, Stephen T.] Mayo Clin, Rochester, MN USA. [Kardia, Sharon L. R.] Univ Michigan, Ann Arbor, MI 48109 USA. [Stafford, Jeanette M.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Ding, Jingzhong] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Barlassina, Cristina; Cusi, Daniele; Salvi, Erika] Univ Milan, Dept Hlth Sci, Milan, Italy. [Cusi, Daniele] San Paolo Hosp, Div Nephrol, Milan, Italy. [Staessen, Jan A.] Maastricht Univ, Dept Epidemiol, NL-6200 MD Maastricht, Netherlands. [Staessen, Jan A.] Univ Leuven, Dept Cardiovasc Sci, Div Hypertens & Cardiovasc Rehabil, Studies Coordinating Ctr, Leuven, Belgium. [Grallert, Harald; Meisinger, Christa] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany. [Grallert, Harald] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany. [Grallert, Harald] German Ctr Diabet Res, Neuherberg, Germany. [Mueller-Nurasyid, Martina] DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany. [Mueller-Nurasyid, Martina; Heid, Iris M.] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Kraemer, Bernhard K.] Heidelberg Univ, Univ Med Ctr Mannheim, Dept Med 5, Mannheim, Germany. [Rosas, Sylvia E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Rosas, Sylvia E.] Harvard Univ, Sch Med, Beth Israel Med Ctr, Boston, MA USA. [Nolte, Ilja M.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Nolte, Ilja M.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol FA40, Unit Genet Epidemiol & Bioinformat, NL-9713 AV Groningen, Netherlands. [Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Dept Psychiat, Amsterdam, Netherlands. [Penninx, Brenda W.] NESDA, EMGO Inst Vumc, Amsterdam, Netherlands. [Franke, Andre] Inst Clin Mol Biol, Kiel, Germany. [Noethlings, Ute] Univ Hosp Schleswig Holstein, Popgen Biobank, Kiel, Germany. [Noethlings, Ute] Univ Kiel, Inst Expt Med, Epidemiol Sect, Kiel, Germany. [Lieb, Wolfgang] Univ Kiel, Inst Epidemiol, Kiel, Germany. [Lieb, Wolfgang] Univ Kiel, Biobank Popgen, Kiel, Germany. [Bakker, Stephan J. L.; Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands. [van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Dehghan, Abbas; Hofman, Albert; Rivadeneira, Fernando; Sedaghat, Sanaz; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Coassin, Stefan; Haun, Margot; Kollerits, Barbara; Kronenberg, Florian] Med Univ Innsbruck, Div Genet Epidemiol, A-6020 Innsbruck, Austria. [Paulweber, Bernhard] Paracelsus Private Med Univ Salzburg, Dept Internal Med 1, Salzburg, Austria. [Aumann, Nicole] Univ Med Greifswald, Inst Community Med, Dept SHIP KEF, Greifswald, Germany. [Endlich, Karlhans] Univ Med Greifswald, Inst Anat & Cell Biol, Greifswald, Germany. [Pietzner, Mike] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Rettig, Rainer] Ernst Moritz Arndt Univ Greifswald, Inst Physiol, Greifswald, Germany. [Chouraki, Vincent] Univ Lille Nord France, Inst Pasteur Lille, INSERM, U744,CHR&U Lille,Serv Epidemiol Reg,CHRU, Lille, France. [Helmer, Catherine] Univ Bordeaux 2, ISPED, INSERM, U897, F-33076 Bordeaux, France. [Lambert, Jean-Charles] Univ Lille Nord France, Inst Pasteur Lille, INSERM, U744, Lille, France. [Stengel, Benedicte] Univ Paris 11, INSERM, U1018, CESP Team 10, Villejuif, France. [Lehtimaki, Terho; Lyytikainen, Leo-Pekka] Fimlab Labs, Dept Clin Chem, Tampere, Finland. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Johnson, Andrew] NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Framingham Heart Study, Framingham, MA USA. [Bochud, Murielle] Univ Lausanne Hosp, Inst Social & Prevent Med IUMSP, Epalinges, Switzerland. [Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Gastroenterol, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Goessling, Wolfram] Broad Inst MIT & Harvard, Cambridge, MA USA. [Kottgen, Anna] Freiburg Univ Clin, Div Renal, Freiburg, Germany. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA. RP Boger, CA (reprint author), Univ Hosp Regensburg, Dept Nephrol, Franz Josef Strauss Allee 11, D-93042 Regensburg, Germany. EM carsten.boeger@klinik.uni-regensburg.de RI Lyytikainen, Leo-Pekka/C-8544-2016; Stengel, Benedicte/G-5730-2015; Cossette, Suzanne/I-8008-2016; Lambert, jean-charles/A-9553-2014; Smith, Albert/K-5150-2015; Bochud, Murielle/A-3981-2010; Johnson, Andrew/G-6520-2013; Franke, Andre/B-2151-2010; Lieb, Wolfgang/C-1990-2012; Rivadeneira, Fernando/O-5385-2015; lambert, jean-charles/F-8787-2013; Kronenberg, Florian/B-1736-2008; Colaus, PsyColaus/K-6607-2013; Grallert, Harald/B-3424-2013; HELMER, Catherine/I-6581-2015; Bakker, Stephan/J-4023-2015; Staessen, Jan/A-1065-2011; Gudnason, Vilmundur/K-6885-2015; Aspelund, Thor/C-5983-2008; Woodward, Mark/D-8492-2015; Wang, Jie Jin/P-1499-2014; Mitchell, Paul/P-1498-2014 OI Goessling, Wolfram/0000-0001-9972-1569; Meisinger, Christa/0000-0002-9026-6544; Salvi, Erika/0000-0002-2724-2291; Mitchell, Braxton/0000-0003-4920-4744; Dehghan, Abbas/0000-0001-6403-016X; Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Lambert, jean-charles/0000-0003-0829-7817; Smith, Albert/0000-0003-1942-5845; Bochud, Murielle/0000-0002-5727-0218; Franke, Andre/0000-0003-1530-5811; McMahon, Gearoid/0000-0002-7723-2198; Rivadeneira, Fernando/0000-0001-9435-9441; Kronenberg, Florian/0000-0003-2229-1120; HELMER, Catherine/0000-0002-5169-7421; Bakker, Stephan/0000-0003-3356-6791; Staessen, Jan/0000-0002-3026-1637; Gudnason, Vilmundur/0000-0001-5696-0084; Aspelund, Thor/0000-0002-7998-5433; Wang, Jie Jin/0000-0001-9491-4898; FU NIH [N01-AG-1-2100, R01 AG18728, R01 HL088119, U01 GM074518-04, U01 HL072515-06, U01 HL084756, K12RR023250, NIH P30 DK072488]; NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); University of Maryland General Clinical Research Center [M01 RR 16500]; Baltimore Veterans Administration Medical Center Geriatrics Research and Education Clinical Center; National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C]; component of the National Institutes of Health and NIH Roadmap for Medical Research [UL1RR025005]; (Emmy Noether Programme) of the German Research Foundation [KO3598/2- 1]; Austrian Science Fond (FWF) [P20545-P05, P20545-P05 and P13180] FX AGES: This study has been funded by NIH contract N01-AG-1-2100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, VSN: 00-063. We are indebted to the participants for their willingness to participate in the study.; AMISH: The Amish studies are supported by grants and contracts from the NIH including R01 AG18728 (Amish Longevity Study), R01 HL088119 (Amish Calcification Study), U01 GM074518-04 (PAPI Study), U01 HL072515-06 (HAPI Study), U01 HL084756 and NIH K12RR023250 (University of Maryland MCRDP), NIH P30 DK072488 (Clinical Nutrition Research Unit), the University of Maryland General Clinical Research Center, grant M01 RR 16500, and the Baltimore Veterans Administration Medical Center Geriatrics Research and Education Clinical Center. We thank our Amish research volunteers for their long-standing partnership in research, and the research staff at the Amish Research Clinic for their hard work and dedication.; The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. We thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. AK was supported by the grant KO3598/2- 1 (Emmy Noether Programme) of the German Research Foundation.; ASPS: The research reported in this article was funded by the Austrian Science Fond (FWF) grant number P20545-P05 and P13180. The Medical University of Graz supports the databank of the ASPS. The authors thank the staff and the participants of the ASPS for their valuable contributions. We thank Birgit Reinhart for her long-term administrative commitment and Ing Johann Semmler for the technical assistance at creating the DNA bank. NR 53 TC 15 Z9 15 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2015 VL 87 IS 5 BP 1017 EP 1029 DI 10.1038/ki.2014.361 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA CH5HS UT WOS:000354066900019 PM 25493955 ER PT J AU Roschewski, M Dunleavy, K Pittaluga, S Moorhead, M Pepin, F Kong, K Shovlin, M Jaffe, ES Staudt, LM Lai, C Steinberg, SM Chen, CC Zheng, JB Willis, TD Faham, M Wilson, WH AF Roschewski, Mark Dunleavy, Kieron Pittaluga, Stefania Moorhead, Martin Pepin, Francois Kong, Katherine Shovlin, Margaret Jaffe, Elaine S. Staudt, Louis M. Lai, Catherine Steinberg, Seth M. Chen, Clara C. Zheng, Jianbiao Willis, Thomas D. Faham, Malek Wilson, Wyndham H. TI Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study SO LANCET ONCOLOGY LA English DT Article ID DOSE-ADJUSTED EPOCH; FDG-PET; RITUXIMAB; TOMOGRAPHY; THERAPY; INTERIM; TRANSPLANTATION; CLASSIFICATION; CHEMOTHERAPY; LEUKEMIA AB Background Diff use large-B-cell lymphoma is curable, but when treatment fails, outcome is poor. Although imaging can help to identify patients at risk of treatment failure, they are often imprecise, and radiation exposure is a potential health risk. We aimed to assess whether circulating tumour DNA encoding the clonal immunoglobulin gene sequence could be detected in the serum of patients with diffuse large-B-cell lymphoma and used to predict clinical disease recurrence after frontline treatment. Methods We used next-generation DNA sequencing to retrospectively analyse cell-free circulating tumour DNA in patients assigned to one of three treatment protocols between May 8, 1993, and June 6, 2013. Eligible patients had diffuse large-B-cell lymphoma, no evidence of indolent lymphoma, and were previously untreated. We obtained serial serum samples and concurrent CT scans at specified times during most treatment cycles and up to 5 years of follow-up. VDJ gene segments of the rearranged immunoglobulin receptor genes were amplified and sequenced from pretreatment specimens and serum circulating tumour DNA encoding the VDJ rearrangements was quantitated. Findings Tumour clonotypes were identified in pretreatment specimens from 126 patients who were followed up for a median of 11 years (IQR 6.8-14.2). Interim monitoring of circulating tumour DNA at the end of two treatment cycles in 108 patients showed a 5-year time to progression of 41.7% (95% CI 22.2-60.1) in patients with detectable circulating tumour DNA and 80.2% (69.6-87.3) in those without detectable circulating tumour DNA (p<0.0001). Detectable interim circulating tumour DNA had a positive predictive value of 62.5% (95% CI 40.6-81.2) and a negative predictive value of 79.8% (69.6-87.8). Surveillance monitoring of circulating tumour DNA was done in 107 patients who achieved complete remission. A Cox proportional hazards model showed that the hazard ratio for clinical disease progression was 228 (95% CI 51-1022) for patients who developed detectable circulating tumour DNA during surveillance compared with patients with undetectable circulating tumour DNA (p<0.0001). Surveillance circulating tumour DNA had a positive predictive value of 88.2% (95% CI 63.6-98.5) and a negative predictive value of 97.8% (92.2-99.7) and identified risk of recurrence at a median of 3.5 months (range 0-200) before evidence of clinical disease. Interpretation Surveillance circulating tumour DNA identifies patients at risk of recurrence before clinical evidence of disease in most patients and results in a reduced disease burden at relapse. Interim circulating tumour DNA is a promising biomarker to identify patients at high risk of treatment failure. C1 [Roschewski, Mark; Dunleavy, Kieron; Shovlin, Margaret; Staudt, Louis M.; Lai, Catherine; Wilson, Wyndham H.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Off Clin Director, Ctr Canc Res, Bethesda, MD 20892 USA. [Moorhead, Martin; Pepin, Francois; Kong, Katherine; Zheng, Jianbiao; Willis, Thomas D.; Faham, Malek] Adapt Biotechnol, San Francisco, CA USA. [Chen, Clara C.] NIH, Div Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), NCI, Lymphoma Therapeut Sect, Lymphoid Malignancies Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov FU National Cancer Institute; Adaptive Biotechnologies FX This study was funded by the National Cancer Institute and Adaptive Biotechnologies. NR 30 TC 40 Z9 44 U1 4 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2015 VL 16 IS 5 BP 541 EP 549 DI 10.1016/S1470-2045(15)70106-3 PG 9 WC Oncology SC Oncology GA CH3DW UT WOS:000353908200048 PM 25842160 ER PT J AU Lowy, DR Herrero, R Hildesheim, A AF Lowy, Douglas R. Herrero, Rolando Hildesheim, Allan CA IARC NCI Workshop Primary Endpoin TI Primary endpoints for future prophylactic human papillomavirus vaccine trials: towards infection and immunobridging SO LANCET ONCOLOGY LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; CERVICAL-CANCER; AS04-ADJUVANTED VACCINE; HPV INFECTION; ANTIBODY-RESPONSES; PARTICLE VACCINE; 2-DOSE SCHEDULE; DOUBLE-BLIND; GRADE 3; WOMEN AB Although available human papillomavirus (HPV) vaccines have high efficacy against incident infection and disease caused by HPV types that they specifically target, new vaccine trials continue to be needed. The goals of these trials could include change of vaccine dose or route of administration (or both), development of second-generation vaccines, and the regional manufacture of biosimilar vaccines. We summarise present thinking about primary endpoints for HPV vaccine trials as developed at an experts workshop convened by the International Agency for Research on Cancer and the US National Cancer Institute in September, 2013. Efficacy trials that have led to licensure for cervical cancer prevention have used the disease endpoint of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). However, on the basis of experience from the trials and present knowledge of HPV infection, future efficacy trials for new vaccines can be safely streamlined by the use of persistent HPV infection, which occurs more frequently than CIN2+, and can be more reproducibly measured as a primary endpoint. Immunobridging trials can be sufficient to ascertain immunological non-inferiority for licensure for alternate dosing schedules, bridging to age 26 years or younger, and biosimilar vaccines, with post-licensure surveillance confirming effectiveness. These recommendations are intended to help stimulate continued vaccine development while ensuring appropriate assessment of safety and efficacy. C1 [Lowy, Douglas R.] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. [Herrero, Rolando] Int Agcy Res Canc, Prevent & Implementat Grp, Sect Early Detect & Prevent, F-69372 Lyon, France. [Hildesheim, Allan] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Lowy, DR (reprint author), NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. EM lowyd@mail.nih.gov RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU Intramural Research Program, National Cancer Institute, National Institutes of Health FX This Series paper was borne out of the International Agency for Research on Cancer and the US National Cancer Institute workshop on Primary Endpoints for Prophylactic HPV Vaccine Trials. We thank Gary Clifford, Linda Eckert, Aimee Kreimer, Suzanne Kruger-Kjaer, Lauri Markowitz, Pieter Neels, Martyn Plummer, Jeff Roberts, Rengaswamy Sankaranarayanan, Mahboobeh Safaeian, Vivien Davis Tsu, Elizabeth R Unger, Salvatore Vaccarella, Sholom Wacholder, and Christopher Wild. DRL and AH are employed by the National Cancer Institute, National Institutes of Health. This Series paper is supported in part by the Intramural Research Program, National Cancer Institute, National Institutes of Health. NR 44 TC 15 Z9 16 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2015 VL 16 IS 5 BP E226 EP E233 PG 8 WC Oncology SC Oncology GA CH3DW UT WOS:000353908200024 PM 25943067 ER PT J AU Schiller, JT Muller, M AF Schiller, John T. Mueller, Martin TI Next generation prophylactic human papillomavirus vaccines SO LANCET ONCOLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; INTRAEPITHELIAL NEOPLASIA; VACCINATION PROGRAM; IMMUNE-RESPONSES; QUADRIVALENT VACCINE; CERVICAL-CANCER; HPV VACCINES; YOUNG-WOMEN; L1; IMMUNOGENICITY AB The two licensed bivalent and quadrivalent human papillomavirus (HPV) L1 (the major papillomavirus virion protein) virus-like particle (VLP) vaccines are regarded as safe, effective, and well established prophylactic vaccines. However, they have some inherent limitations, including a fairly high production and delivery cost, virus-type restricted protection, and no reported therapeutic activity, which might be addressed with the development of alternative dosing schedules and vaccine products. A change from a three-dose to a two-dose protocol for the licensed HPV vaccines, especially in younger adolescents (aged 9-13 years), is underway in several countries and is likely to become the future norm. Preliminary evidence suggests that recipients of HPV vaccines might derive prophylactic benefits from one dose of the bivalent vaccine. Substantial interest exists in both the academic and industrial sectors in the development of second-generation L1 VLP vaccines in terms of cost reduction-eg, by production in Escherichia coli or alternative types of yeast. However, Merck's nonavalent vaccine, produced via the Saccharomyces cerevisiae production system that is also used for their quadrivalent vaccine, is the first second-generation HPV VLP vaccine to be available on the market. By contrast, other pharmaceutical companies are developing microbial vectors that deliver L1 genes. These two approaches would add an HPV component to existing live attenuated vaccines for measles and typhoid fever. Prophylactic vaccines that are based on induction of broadly cross-neutralising antibodies to L2, the minor HPV capsid protein, are also being developed both as simple monomeric fusion proteins and as virus-like display vaccines. The strong interest in developing the next generation of vaccines, particularly by manufacturers in middle-to-high income countries, increases the likelihood that vaccine production will become decentralised with the hope that effective HPV vaccines will be made increasingly available in low-resource settings where they are most needed. C1 [Schiller, John T.] NCI, NIH, Bethesda, MD 20892 USA. [Mueller, Martin] Deutsch Krebsforschungszentrum, Heidelberg, Germany. RP Schiller, JT (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM schillej@mail.nih.gov FU Merck FX JTS in an inventor on US Government-owned patents related to papillomavirus virus-like particle vaccines licensed to Merck and GlaxoSmithKline (GSK), and patents related to papillomavirus L2 vaccines licensed to Sanofi Pasteur and GSK. MM is an inventor and in receipt of royalties of patents related to virus-like particle vaccines owned by Loyola University Chicago (Chicago, USA) and licensed to GSK. MM is an inventor of Trx-L2 vaccines and received personal fees from Merck for analyses of clinical trial sera. NR 72 TC 12 Z9 15 U1 4 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2015 VL 16 IS 5 BP E217 EP E225 PG 9 WC Oncology SC Oncology GA CH3DW UT WOS:000353908200023 PM 25943066 ER PT J AU Rao, M AF Rao, Mahendra TI National Institutes of Health: A Catalyst in Advancing Regenerative Medicine Science Into Practice SO MAYO CLINIC PROCEEDINGS LA English DT Article ID PERSONALIZED GENOMIC MEDICINE; PLURIPOTENT STEM-CELLS; THERAPY AB The stem cell domain of the regenerative medicine field has seen fundamental changes initiated by seminal discoveries in cell biology, genetic engineering, and whole genome sequencing. Many of these discoveries were funded in part by the National Institutes of Health (NIH), and the NIH remains a leader in supporting research in the United States. However, as the field has developed, the NIH has responded proactively to identify roadblocks and to develop solutions that will accelerate translation of basic discoveries to the clinical setting. These activities range from organizing specialized workshops and coordinating activities among international organizations and the different arms of the government to funding small-scale industry. In addition, the NIH has been a key driver in providing needed infrastructure in areas in which the private sector has been unable to, or does not believe it can, invest. These activities of the NIH are as important as its traditional funding role, and I believe they have contributed to the innovation and rapid pace of discovery in this field. (C) 2015 Mayo Foundation for Medical Education and Research C1 [Rao, Mahendra] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA. RP Rao, M (reprint author), New York Stem Cell Fdn, 1995 Broadway,Ste 600, New York, NY 10023 USA. EM mrao@qthera.com NR 29 TC 1 Z9 1 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD MAY PY 2015 VL 90 IS 5 BP 672 EP 679 DI 10.1016/j.mayocp.2013.05.038 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CH2TG UT WOS:000353876900017 PM 25939939 ER PT J AU Cornelis, MC Byrne, EM Esko, T Nalls, MA Ganna, A Paynter, N Monda, KL Amin, N Fischer, K Renstrom, F Ngwa, JS Huikari, V Cavadino, A Nolte, IM Teumer, A Yu, K Marques-Vidal, P Rawal, R Manichaikul, A Wojczynski, MK Vink, JM Zhao, JH Burlutsky, G Lahti, J Mikkila, V Lemaitre, RN Eriksson, J Musani, SK Tanaka, T Geller, F Luan, J Hui, J Magi, R Dimitriou, M Garcia, ME Ho, WK Wright, MJ Rose, LM Magnusson, PKE Pedersen, NL Couper, D Oostra, BA Hofman, A Ikram, MA Tiemeier, HW Uitterlinden, AG van Rooij, FJA Barroso, I Johansson, I Xue, L Kaakinen, M Milani, L Power, C Snieder, H Stolk, RP Baumeister, SE Biffar, R Gu, F Bastardot, F Kutalik, Z Jacobs, DR Forouhi, NG Mihailov, E Lind, L Lindgren, C Michaelsson, K Morris, A Jensen, M Khaw, KT Luben, RN Wang, JJ Mannisto, S Perala, MM Kahonen, M Lehtimaki, T Viikari, J Mozaffarian, D Mukamal, K Psaty, BM Doring, A Heath, AC Montgomery, GW Dahmen, N Carithers, T Tucker, KL Ferrucci, L Boyd, HA Melbye, M Treur, JL Mellstrom, D Hottenga, JJ Prokopenko, I Tonjes, A Deloukas, P Kanoni, S Lorentzon, M Houston, DK Liu, Y Danesh, J Rasheed, A Mason, MA Zonderman, AB Franke, L Kristal, BS Karjalainen, J Reed, DR Westra, HJ Evans, MK Saleheen, D Harris, TB Dedoussis, G Curhan, G Stumvoll, M Beilby, J Pasquale, LR Feenstra, B Bandinelli, S Ordovas, JM Chan, AT Peters, U Ohlsson, C Gieger, C Martin, NG Waldenberger, M Siscovick, DS Raitakari, O Eriksson, JG Mitchell, P Hunter, DJ Kraft, P Rimm, EB Boomsma, DI Borecki, IB Loos, RJF Wareham, NJ Vollenweider, P Caporaso, N Grabe, HJ Neuhouser, ML Wolffenbuttel, BHR Hu, FB Hypponen, E Jarvelin, MR Cupples, LA Franks, PW Ridker, PM van Duijn, CM Heiss, G Metspalu, A North, KE Ingelsson, E Nettleton, JA van Dam, RM Chasman, DI AF Cornelis, M. C. Byrne, E. M. Esko, T. Nalls, M. A. Ganna, A. Paynter, N. Monda, K. L. Amin, N. Fischer, K. Renstrom, F. Ngwa, J. S. Huikari, V. Cavadino, A. Nolte, I. M. Teumer, A. Yu, K. Marques-Vidal, P. Rawal, R. Manichaikul, A. Wojczynski, M. K. Vink, J. M. Zhao, J. H. Burlutsky, G. Lahti, J. Mikkila, V. Lemaitre, R. N. Eriksson, J. Musani, S. K. Tanaka, T. Geller, F. Luan, J. Hui, J. Maegi, R. Dimitriou, M. Garcia, M. E. Ho, W-K Wright, M. J. Rose, L. M. Magnusson, P. K. E. Pedersen, N. L. Couper, D. Oostra, B. A. Hofman, A. Ikram, M. A. Tiemeier, H. W. Uitterlinden, A. G. van Rooij, F. J. A. Barroso, I. Johansson, I. Xue, L. Kaakinen, M. Milani, L. Power, C. Snieder, H. Stolk, R. P. Baumeister, S. E. Biffar, R. Gu, F. Bastardot, F. Kutalik, Z. Jacobs, D. R., Jr. Forouhi, N. G. Mihailov, E. Lind, L. Lindgren, C. Michaelsson, K. Morris, A. Jensen, M. Khaw, K-T Luben, R. N. Wang, J. J. Mannisto, S. Perala, M-M Kahonen, M. Lehtimaki, T. Viikari, J. Mozaffarian, D. Mukamal, K. Psaty, B. M. Doering, A. Heath, A. C. Montgomery, G. W. Dahmen, N. Carithers, T. Tucker, K. L. Ferrucci, L. Boyd, H. A. Melbye, M. Treur, J. L. Mellstrom, D. Hottenga, J. J. Prokopenko, I. Toenjes, A. Deloukas, P. Kanoni, S. Lorentzon, M. Houston, D. K. Liu, Y. Danesh, J. Rasheed, A. Mason, M. A. Zonderman, A. B. Franke, L. Kristal, B. S. Karjalainen, J. Reed, D. R. Westra, H-J Evans, M. K. Saleheen, D. Harris, T. B. Dedoussis, G. Curhan, G. Stumvoll, M. Beilby, J. Pasquale, L. R. Feenstra, B. Bandinelli, S. Ordovas, J. M. Chan, A. T. Peters, U. Ohlsson, C. Gieger, C. Martin, N. G. Waldenberger, M. Siscovick, D. S. Raitakari, O. Eriksson, J. G. Mitchell, P. Hunter, D. J. Kraft, P. Rimm, E. B. Boomsma, D. I. Borecki, I. B. Loos, R. J. F. Wareham, N. J. Vollenweider, P. Caporaso, N. Grabe, H. J. Neuhouser, M. L. Wolffenbuttel, B. H. R. Hu, F. B. Hyppoenen, E. Jarvelin, M-R Cupples, L. A. Franks, P. W. Ridker, P. M. van Duijn, C. M. Heiss, G. Metspalu, A. North, K. E. Ingelsson, E. Nettleton, J. A. van Dam, R. M. Chasman, D. I. CA Coffee & Caffeine Genetics Consort Int Parkinson's Dis Genomics Conso North Amer Brain Expression Consor UK Brain Expression Consortium TI Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption SO MOLECULAR PSYCHIATRY LA English DT Article ID CAFFEINE; PROTEIN; VARIANTS; RECEPTOR; BRAIN; GLUCOKINASE; INVOLVEMENT; BINDING; BDNF AB Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in similar to 30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log(10)Bayes factor (BF) > 5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P < 5x10(-8)). Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee. C1 [Cornelis, M. C.; Mozaffarian, D.; Curhan, G.; Pasquale, L. R.; Chan, A. T.; Hunter, D. J.; Rimm, E. B.; Hu, F. B.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02215 USA. [Cornelis, M. C.; Jensen, M.; Mozaffarian, D.; Rimm, E. B.; Hu, F. B.; Franks, P. W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. [Byrne, E. M.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. [Esko, T.; Fischer, K.; Maegi, R.; Milani, L.; Mihailov, E.; Metspalu, A.] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Esko, T.] Childrens Hosp Boston, Div Endocrinol, Boston, MA USA. [Esko, T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. [Esko, T.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Nalls, M. A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Ganna, A.; Magnusson, P. K. E.; Pedersen, N. L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Karolinska, Sweden. [Paynter, N.; Rose, L. M.; Ridker, P. M.; Chasman, D. I.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. [Monda, K. L.; Heiss, G.; North, K. E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Amin, N.; Hofman, A.; Ikram, M. A.; Tiemeier, H. W.; Uitterlinden, A. G.; van Rooij, F. J. A.; van Duijn, C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Renstrom, F.; Franks, P. W.] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Ngwa, J. S.; Xue, L.; Cupples, L. A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Huikari, V.; Kaakinen, M.; Jarvelin, M-R] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Cavadino, A.; Power, C.; Hyppoenen, E.] UCL, Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, Ctr Epidemiol Child Hlth,MRC, London, England. [Nolte, I. M.; Snieder, H.; Stolk, R. P.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Teumer, A.] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Yu, K.; Gu, F.; Caporaso, N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Marques-Vidal, P.] Univ Lausanne Hosp, Inst Social & Prevent Med, Lausanne, Switzerland. [Rawal, R.; Gieger, C.] Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Munich, Germany. [Manichaikul, A.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Wojczynski, M. K.; Borecki, I. B.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA. [Vink, J. M.; Treur, J. L.; Hottenga, J. J.; Boomsma, D. I.] Vrije Univ Amsterdam, Dept Biol Psychol Netherlands Twin Register, Amsterdam, Netherlands. [Zhao, J. H.; Luan, J.; Forouhi, N. G.; Loos, R. J. F.; Wareham, N. J.] Univ Cambridge, Epidemiol Unit, MRC, Cambridge, England. [Burlutsky, G.; Wang, J. J.; Mitchell, P.] Univ Sydney, Dept Ophthalmol, Ctr Vis Res, Sydney, NSW 2006, Australia. [Burlutsky, G.; Wang, J. J.; Mitchell, P.] Univ Sydney, Westmead Millennium Inst, Sydney, NSW 2006, Australia. [Lahti, J.] Univ Helsinki, Inst Behav Sci, Helsinki, Finland. [Lahti, J.; Eriksson, J. G.] Folkhalsan Res Ctr, Helsinki, Finland. [Mikkila, V.] Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland. [Mikkila, V.; Raitakari, O.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Mikkila, V.; Raitakari, O.] Turku Univ Hosp, FIN-20520 Turku, Finland. [Lemaitre, R. N.; Psaty, B. M.; Siscovick, D. S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Eriksson, J.; Mellstrom, D.; Lorentzon, M.; Ohlsson, C.] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden. [Musani, S. K.] Univ Mississippi, Med Ctr, Jackson, MI USA. [Tanaka, T.; Ferrucci, L.] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. [Geller, F.; Boyd, H. A.; Melbye, M.; Feenstra, B.] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Hui, J.; Beilby, J.] Busselton Populat Med Res Fdn Inc, Busselton, WA, Australia. [Hui, J.; Beilby, J.] PathWest Lab Med, Nedlands, WA, Australia. [Hui, J.; Beilby, J.] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia. [Hui, J.] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia. [Dimitriou, M.; Dedoussis, G.] Harokopio Univ, Athens, Greece. [Garcia, M. E.; Harris, T. B.] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA. [Ho, W-K; Khaw, K-T; Luben, R. N.; Danesh, J.; Saleheen, D.] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England. [Wright, M. J.; Montgomery, G. W.; Martin, N. G.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia. [Couper, D.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Oostra, B. A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Ikram, M. A.] Erasmus MC, Dept Radiol, Rotterdam, Netherlands. [Ikram, M. A.] Erasmus MC, Dept Neurol, Rotterdam, Netherlands. [Tiemeier, H. W.] Erasmus MC, Dept Psychiat, Rotterdam, Netherlands. [Uitterlinden, A. G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Barroso, I.; Deloukas, P.] Wellcome Trust Sanger Inst, Cambridge, England. [Barroso, I.] Univ Cambridge, Metab Res Labs, Cambridge, England. [Barroso, I.] NIHR Cambridge Biomed Res Ctr, Cambridge, England. [Johansson, I.] Umea Univ, Dept Odontol, Umea, Sweden. [Kaakinen, M.; Jarvelin, M-R] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Kaakinen, M.; Jarvelin, M-R] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, MRC Hlth Protect Agcy HPE, Ctr Environm & Hlth,Sch Publ Hlth, London SW7 2AZ, England. [Baumeister, S. 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[Mannisto, S.; Perala, M-M] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Kahonen, M.] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland. [Kahonen, M.; Lehtimaki, T.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Lehtimaki, T.] Univ Tampere, Fimlab Labs, Dept Clin Chem, FIN-33101 Tampere, Finland. [Viikari, J.] Univ Turku, Dept Med, Turku, Finland. [Viikari, J.] Turku Univ Hosp, FIN-20520 Turku, Finland. [Mozaffarian, D.; Rimm, E. B.; Hu, F. B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mozaffarian, D.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Mukamal, K.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Psaty, B. M.; Siscovick, D. S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, B. M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, B. M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Doering, A.] Helmholtz Zentrum Munchen, Inst Epidemiol, Munich, Germany. [Heath, A. C.] Washington Univ, Dept Psychiat, St Louis, MO USA. [Dahmen, N.] Johannes Gutenberg Univ Mainz, Dept Psychiat, Mainz, Germany. [Carithers, T.] Univ Mississippi, Sch Appl Sci, Oxford, MS USA. [Tucker, K. L.] Univ MA Lowell, Clin Lab & Nutr Sci, Lowell, MA USA. [Prokopenko, I.] Univ London Imperial Coll Sci Technol & Med, Dept Genom Common Dis, London, England. [Toenjes, A.; Stumvoll, M.] Univ Leipzig, Dept Med, D-04109 Leipzig, Germany. [Toenjes, A.; Stumvoll, M.] Univ Leipzig, IFB Adipos Dis, D-04109 Leipzig, Germany. [Deloukas, P.; Kanoni, S.] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England. [Deloukas, P.] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Houston, D. K.] Wake Forest Sch Med, Winston Salem, NC USA. [Houston, D. K.; Liu, Y.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Rasheed, A.; Saleheen, D.] Ctr Noncommunicable Dis, Karachi, Pakistan. [Mason, M. A.; Evans, M. K.] NIA, Hlth Dispar Res Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Zonderman, A. B.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. [Franke, L.; Karjalainen, J.; Westra, H-J] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Kristal, B. S.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Kristal, B. S.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Reed, D. R.] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. [Pasquale, L. R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Bandinelli, S.] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy. [Ordovas, J. M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Chan, A. T.] MA Gen Hosp, Div Gastroenterol, Boston, MA USA. [Peters, U.; Neuhouser, M. L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Waldenberger, M.] Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Munich, Germany. [Raitakari, O.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland. [Eriksson, J. G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Eriksson, J. G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Hunter, D. J.; Kraft, P.] Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA. [Loos, R. J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA. [Loos, R. J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA. [Grabe, H. J.] Univ Med Greifswald, HELIOS Hosp Stralsund, Dept Psychiat & Psychotherapy, Greifswald, Germany. [Wolffenbuttel, B. H. R.] Univ Groningen, Dept Endocrinol, Univ Med Ctr Groningen, Groningen, Netherlands. [Hyppoenen, E.] Univ S Australia, Sch Populat Hlth, Adelaide, SA 5001, Australia. [Hyppoenen, E.] South Australian Hlth & Med Res Inst, Adelaide, SA, Australia. [Jarvelin, M-R] Natl Inst Hlth & Welf, Dept Children & Young People & Families, Oulu, Finland. [Jarvelin, M-R] Oulu Univ Hosp, Unit Primary Care, Oulu, Finland. [Cupples, L. A.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Franks, P. W.] Umea Univ, Med Sect, Dept Publ Hlth & Clin Med, Umea, Sweden. [van Duijn, C. M.] Netherlands Consortium Hlth Ageing, Leiden, Netherlands. [van Duijn, C. M.] Natl Genom Initiat, Leiden, Netherlands. [Nettleton, J. A.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA. [van Dam, R. M.] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. [van Dam, R. M.] Natl Univ Singapore, Dept Med, Yong Loo Lin Sch Med, Singapore 117548, Singapore. [van Dam, R. M.] Natl Univ Hlth Syst, Singapore, Singapore. RP Cornelis, MC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 401 Pk Dr, Boston, MA 02215 USA. EM mcorneli@hsph.harvard.edu; dchasman@research.bwh.harvard.edu RI Colaus, PsyColaus/K-6607-2013; Waldenberger, Melanie/B-5355-2014; Prokopenko, Inga/H-3241-2014; Wright, Margaret/A-4560-2016; Hypponen, Elina/B-2596-2014; Deloukas, Panos/B-2922-2013; Franke, Lude/P-7036-2016; Karjalainen, Juha/P-8624-2016; Magnusson, Patrik/C-4458-2017; OI Eriksson, Johan/0000-0002-2516-2060; Zonderman, Alan B/0000-0002-6523-4778; corvol, jean-christophe/0000-0001-7325-0199; Lahti, Jari/0000-0002-4310-5297; Ganna, Andrea/0000-0002-8147-240X; Tiemeier, Henning/0000-0002-4395-1397; Plagnol, Vincent/0000-0002-5597-9215; Ikram, Mohammad Arfan/0000-0003-0372-8585; Esko, Tonu/0000-0003-1982-6569; Gieger, Christian/0000-0001-6986-9554; van Dam, Rob/0000-0002-7354-8734; Mannisto, Satu/0000-0002-8668-3046; Mellstrom, Dan/0000-0003-2761-3723; Luben, Robert/0000-0002-5088-6343; Wolffenbuttel, Bruce H.R./0000-0001-9262-6921; Forouhi, Nita/0000-0002-5041-248X; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Waldenberger, Melanie/0000-0003-0583-5093; Prokopenko, Inga/0000-0003-1624-7457; Wright, Margaret/0000-0001-7133-4970; Hypponen, Elina/0000-0003-3670-9399; Deloukas, Panos/0000-0001-9251-070X; Franke, Lude/0000-0002-5159-8802; Kaakinen, Marika/0000-0002-9228-0462; HO, WEANG KEE/0000-0002-8269-7344; Magi, Reedik/0000-0002-2964-6011 NR 43 TC 19 Z9 20 U1 5 U2 46 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 2015 VL 20 IS 5 BP 647 EP 656 DI 10.1038/mp.2014.107 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CH0JS UT WOS:000353706400016 ER PT J AU Corrigan-Curay, J O'Reilly, M Kohn, DB Cannon, PM Bao, G Bushman, FD Carroll, D Cathomen, T Joung, JK Roth, D Sadelain, M Scharenberg, AM von Kalle, C Zhang, F Jambou, R Rosenthal, E Hassani, M Singh, A Porteus, MH AF Corrigan-Curay, Jacqueline O'Reilly, Marina Kohn, Donald B. Cannon, Paula M. Bao, Gang Bushman, Frederic D. Carroll, Dana Cathomen, Toni Joung, J. Keith Roth, David Sadelain, Michel Scharenberg, Andrew M. von Kalle, Christof Zhang, Feng Jambou, Robert Rosenthal, Eugene Hassani, Morad Singh, Aparna Porteus, Matthew H. TI Genome Editing Technologies: Defining a Path to Clinic SO MOLECULAR THERAPY LA English DT News Item ID ZINC-FINGER NUCLEASES; ACUTE LYMPHOBLASTIC-LEUKEMIA; RAG-MEDIATED RECOMBINATION; MAMMALIAN-CELLS; GENE-THERAPY; IN-VITRO; T-CELLS; DNA; SPECIFICITY; CHALLENGES C1 [Corrigan-Curay, Jacqueline; O'Reilly, Marina; Jambou, Robert; Rosenthal, Eugene; Hassani, Morad; Singh, Aparna] NIH, Bethesda, MD 20892 USA. [Kohn, Donald B.] Univ Calif Los Angeles, Los Angeles, CA USA. [Cannon, Paula M.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Bao, Gang] Georgia Inst Technol, Atlanta, GA 30332 USA. [Bushman, Frederic D.; Roth, David] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Carroll, Dana] Univ Utah, Sch Med, Salt Lake City, UT USA. [Cathomen, Toni] Univ Med Ctr, Freiberg, Germany. [Joung, J. Keith] Massachusetts Gen Hosp, Charlestown, MA USA. [Joung, J. Keith] Harvard Univ, Sch Med, Boston, MA USA. [Sadelain, Michel] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Scharenberg, Andrew M.] Seattle Childrens Res Inst, Seattle, WA USA. [Scharenberg, Andrew M.] Univ Washington, Sch Med, Seattle, WA USA. [von Kalle, Christof] Natl Ctr Tumor Dis, Heidelberg, Germany. [von Kalle, Christof] German Canc Res Ctr, Heidelberg, Germany. [Zhang, Feng] MIT, Cambridge, MA 02139 USA. [Zhang, Feng] Harvard Univ, Cambridge, MA 02138 USA. [Porteus, Matthew H.] Stanford Univ, Stanford, CA 94305 USA. RP Corrigan-Curay, J (reprint author), NIH, Off Sci Policy, 6705 Rockledge Dr, Bethesda, MD 20892 USA. EM corrigaja@nhlbi.nih.gov OI Cathomen, Toni/0000-0002-7757-4630 NR 43 TC 25 Z9 25 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2015 VL 23 IS 5 BP 796 EP 806 DI 10.1038/mt.2015.54 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CH3LW UT WOS:000353933200002 PM 25943494 ER PT J AU Gowdy, KM Madenspacher, JH Azzam, KM Gabor, KA Janardhan, KS Aloor, JJ Fessler, MB AF Gowdy, K. M. Madenspacher, J. H. Azzam, K. M. Gabor, K. A. Janardhan, K. S. Aloor, J. J. Fessler, M. B. TI Key role for scavenger receptor B-I in the integrative physiology of host defense during bacterial pneumonia SO MUCOSAL IMMUNOLOGY LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; HIGH-DENSITY-LIPOPROTEIN; VITAMIN-E; SR-BI; ALVEOLAR EPITHELIUM; ENDOTHELIAL-CELLS; ESCHERICHIA-COLI; HDL RECEPTOR; LUNG INJURY; INFECTION AB Scavenger receptor B-I (SR-BI) is a multirecognition receptor that regulates cholesterol trafficking and cardiovascular inflammation. Although it is expressed by neutrophils (PMNs) and lung-resident cells, no role for SR-BI has been defined in pulmonary immunity. Herein, we report that, compared with SR-BI+/+ counterparts, SR-BI-/- mice suffer markedly increased mortality during bacterial pneumonia associated with higher bacterial burden in the lung and blood, deficient induction of the stress glucocorticoid corticosterone, higher serum cytokines, and increased organ injury. SR-BI-/- mice had significantly increased PMN recruitment and cytokine production in the infected airspace. This was associated with defective hematopoietic cell-dependent clearance of lipopolysaccharide from the airspace and increased cytokine production by SR-BI-/- macrophages. Corticosterone replacement normalized alveolar neutrophilia but not alveolar cytokines, bacterial burden, or mortality, suggesting that adrenal insufficiency derepresses PMN trafficking to the SR-BI-/- airway in a cytokine-independent manner. Despite enhanced alveolar neutrophilia, SR-BI-/- mice displayed impaired phagocytic killing. Bone marrow chimeras revealed this defect to be independent of the dyslipidemia and adrenal insufficiency of SR-BI-/- mice. During infection, SR-BI-/- PMNs displayed deficient oxidant production and CD11b externalization, and increased surface L-selectin, suggesting defective activation. Taken together, SR-BI coordinates several steps in the integrated neutrophilic host defense response to pneumonia. C1 [Gowdy, K. M.; Madenspacher, J. H.; Azzam, K. M.; Gabor, K. A.; Aloor, J. J.; Fessler, M. B.] NIEHS, Div Intramural Res, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. [Janardhan, K. S.] NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. [Janardhan, K. S.] NIH, Integrated Lab Syst Inc, Res Triangle Pk, NC USA. RP Gowdy, KM (reprint author), NIEHS, Div Intramural Res, Lab Resp Biol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM kymberly.gowdy@nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES102005] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01 ES102005). We thank Drs Donald Cook and Seddon Thomas for manuscript review and Ralph Wilson, Debra King, Ligon Perrow, Maria Sifre, Carl Bortner, and CJ Tucker for their technical assistance. NR 49 TC 2 Z9 2 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD MAY PY 2015 VL 8 IS 3 BP 559 EP 571 DI 10.1038/mi.2014.88 PG 13 WC Immunology SC Immunology GA CH5OR UT WOS:000354085700011 PM 25336169 ER PT J AU Schindler, C Chen, Y Pu, J Guo, XL Bonifacino, JS AF Schindler, Christina Chen, Yu Pu, Jing Guo, Xiaoli Bonifacino, Juan S. TI EARP is a multisubunit tethering complex involved in endocytic recycling SO NATURE CELL BIOLOGY LA English DT Article ID TRANS-GOLGI NETWORK; SYNTAXIN 6; RETROGRADE TRANSPORT; STRUCTURE PREDICTION; HIPPOCAMPAL-NEURONS; GLUCOSE-TRANSPORT; 3T3-L1 ADIPOCYTES; STRUCTURAL BASIS; SNARE COMPLEXES; CELL-MIGRATION AB Recycling of endocytic receptors to the cell surface involves passage through a series of membrane-bound compartments by mechanisms that are poorly understood. In particular, it is unknown if endocytic recycling requires the function of multisubunit tethering complexes, as is the case for other intracellular trafficking pathways. Herein we describe a tethering complex named endosome-associated recycling protein (EARP) that is structurally related to the previously described Golgi-associated retrograde protein (GARP) complex. The two complexes share the Ang2, Vps52 and Vps53 subunits, but EARP contains an uncharacterized protein, syndetin, in place of the Vps54 subunit of GARP. This change determines differential localization of EARP to recycling endosomes and GARP to the Golgi complex. EARP interacts with the target SNARE syntaxin 6 and various cognate SNAREs. Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface. These findings implicate EARP in canonical membrane-fusion events in the process of endocytic recycling. C1 [Schindler, Christina; Chen, Yu; Pu, Jing; Guo, Xiaoli; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. EM bonifacinoj@helix.nih.gov OI Bonifacino, Juan S./0000-0002-5673-6370 FU Intramural Program of NICHD, NIH [ZIA HD001607] FX We thank X. Zhu and N. Tsal for technical assistance, J. Presley for discussions and R. Mattera and D. Gershlick for critical review of the manuscript. This work is funded by the Intramural Program of NICHD, NIH (ZIA HD001607). NR 63 TC 11 Z9 16 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAY PY 2015 VL 17 IS 5 BP 639 EP U229 DI 10.1038/ncb3129 PG 22 WC Cell Biology SC Cell Biology GA CH1HG UT WOS:000353771500012 PM 25799061 ER PT J AU Kang, XL Lu, ZG Cui, CH Deng, M Fan, YQ Dong, BJ Han, X Xie, FC Tyner, JW Coligan, JE Collins, RH Xiao, XS You, MJ Zhang, CC AF Kang, Xunlei Lu, Zhigang Cui, Changhao Deng, Mi Fan, Yuqi Dong, Baijun Han, Xin Xie, Fuchun Tyner, Jeffrey W. Coligan, John E. Collins, Robert H. Xiao, Xiangshu You, M. James Zhang, Cheng Cheng TI The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development SO NATURE CELL BIOLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; IG-LIKE RECEPTOR-1; TYROSINE-PHOSPHATASE SHP-1; PROTEIN-KINASE-I; VIVO; BINDING; TRANSPLANTATION; IDENTIFICATION; MALIGNANCIES; RENEWAL AB Conventional strategies are not particularly successful in the treatment of leukaemia, and identification of signalling pathways crucial to the activity of leukaemia stem cells will provide targets for the development of new therapies. Here we report that certain receptors containing the immunoreceptor tyrosine-based inhibition motif (ITIM) are crucial for the development of acute myeloid leukaemia (AML). Inhibition of expression of the ITIM-containing receptor LAIR1 does not affect normal haematopoiesis but abolishes leukaemia development. LAIR1 induces activation of SHP-1, which acts as a phosphatase-independent signalling adaptor to recruit CAMK1 for activation of downstream CREB in AML cells. The LAIR1-SHP-1-CAMK1-CREB pathway sustains the survival and self-renewal of AML stem cells. Intervention in the signalling initiated by ITIM-containing receptors such as LAIR1 may result in successful treatment of AML. C1 [Kang, Xunlei; Lu, Zhigang; Cui, Changhao; Deng, Mi; Fan, Yuqi; Zhang, Cheng Cheng] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA. [Kang, Xunlei; Lu, Zhigang; Cui, Changhao; Deng, Mi; Fan, Yuqi; Zhang, Cheng Cheng] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA. [Dong, Baijun; You, M. James] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Div Pathol & Lab Med, Houston, TX 77030 USA. [Han, Xin] Univ Texas MD Anderson Canc Ctr, Dept Lab Med, Div Pathol & Lab Med, Houston, TX 77030 USA. [Xie, Fuchun; Xiao, Xiangshu] Oregon Hlth & Sci Univ, Knight Canc Inst, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Tyner, Jeffrey W.] Oregon Hlth & Sci Univ, Knight Canc Inst, Cell & Dev Biol, Portland, OR 97239 USA. [Coligan, John E.] NIAID, Receptor Cell Biol Sect, NIH, Rockville, MD 20852 USA. [Collins, Robert H.] Univ Texas SW Med Ctr Dallas, Internal Med, Dallas, TX 75390 USA. [You, M. James] Univ Texas Grad Sch Biomed Sci Houston, Houston, TX 77030 USA. [Cui, Changhao] Dalian Univ Technol, Sch Life Sci & Med, Panjin 124221, Liaoning, Peoples R China. RP Zhang, CC (reprint author), Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA. EM Alec.Zhang@UTSouthwestern.edu FU NIH [1R01CA172268]; Leukemia & Lymphoma Society [1024-14, TRP-6024-14, CPRIT RP140402]; March of Dimes Foundation [1-FY14-201]; Robert A. Welch Foundation [I-1834]; When Everyone Survives Foundation; V Foundation for Cancer Research; William Lawrence and Blanche Hughes Fund; National Cancer Institute [4 R00CA151457-03]; Leukemia Lymphoma Society; Susan G. Komen Foundation [RO1GM087305]; National Institute Allergy and Infectious Diseases; NIH/NCI [R01 CA164346]; Ladies Leukemia Leaque, Developmental Research Awards in Leukemia [SPORE CA100632]; Center for Inflammation and Cancer; IRG; Center for Genetics and Genomics; Sister Institution Network fund; Physician Scientist Award of the Univmsity of Texas MD Anderson Care Center FX We would lie to thank II. Saya from Keio University School of Medicine for the pMX-IG N-Myc vector. We appreciate the support of staff of the tissue bank at the Department of Hematopathology, the University of Texas MD Anderson Cancer Center. Support to C.C.Z. was from NIH grant 1R01CA172268, Leukemia & Lymphoma Society Awards 1024-14 and TRP-6024-14, CPRIT RP140402, March of Dimes Foundation grant 1-FY14-201, Robert A. Welch Foundation grant I-1834, and When Everyone Survives Foundation. J.W.T. is supported by grants from the V Foundation for Cancer Research, the William Lawrence and Blanche Hughes Fund, and the National Cancer Institute (4 R00CA151457-03), and the Leukemia Lymphoma Society. X.X. is supported by Susan G. Komen Foundation and RO1GM087305. J.W.C. is supported by the intramural program of the National Institute Allergy and Infectious Diseases. M.J.Y. is supported in part by NIH/NCI R01 CA164346, Ladies Leukemia Leaque, Developmental Research Awards in Leukemia SPORE CA100632, and Center for Inflammation and Cancer, IRG, Center for Genetics and Genomics, Sister Institution Network fund and Physician Scientist Award of the Univmsity of Texas MD Anderson Care Center. NR 57 TC 14 Z9 15 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAY PY 2015 VL 17 IS 5 BP 665 EP U286 DI 10.1038/nch3158 PG 28 WC Cell Biology SC Cell Biology GA CH1HG UT WOS:000353771500014 PM 25915125 ER PT J AU Kroeze, WK Sassano, MF Huang, XP Lansu, K McCorvy, JD Giguere, PM Sciaky, N Roth, BL AF Kroeze, Wesley K. Sassano, Maria F. Huang, Xi-Ping Lansu, Katherine McCorvy, John D. Giguere, Patrick M. Sciaky, Noah Roth, Bryan L. TI PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; BETA-ARRESTIN BINDING; OPIOID RECEPTOR; SCREENING ASSAY; ACTIVATION; CELLS; SUBTYPES; IDENTIFICATION; DOPAMINE-D-2; PHARMACOLOGY AB G protein-coupled receptors (GPCRs) are essential mediators of cellular signaling and are important targets of drug action. Of the approximately 350 nonolfactory human GPCRs, more than 100 are still considered to be 'orphans' because their endogenous ligands remain unknown. Here, we describe a unique open-source resource that allows interrogation of the druggable human GPCRome via a G protein-independent beta-arrestin-recruitment assay. We validate this unique platform at more than 120 nonorphan human GPCR targets, demonstrate its utility for discovering new ligands for orphan human GPCRs and describe a method (parallel receptorome expression and screening via transcriptional output, with transcriptional activation following arrestin translocation (PRESTO-Tango)) for the simultaneous and parallel interrogation of the entire human nonolfactory GPCRome. C1 [Kroeze, Wesley K.; Sassano, Maria F.; Huang, Xi-Ping; Lansu, Katherine; McCorvy, John D.; Giguere, Patrick M.; Sciaky, Noah; Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Kroeze, Wesley K.; Sassano, Maria F.; Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC USA. [Roth, Bryan L.] Univ N Carolina, Program Neurosci, Chapel Hill, NC USA. [Roth, Bryan L.] Univ N Carolina, Div Chem Biol & Med Chem, Chapel Hill, NC USA. RP Roth, BL (reprint author), Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. EM bryan_roth@med.unc.edu RI Roth, Bryan/F-3928-2010 FU US National Institutes of Health [R01DA27170, UO1MH104974]; US National Institute of Mental Health Psychoactive Drug Screening Program; Michael Hooker Distinguished Professorship; University of North Carolina Department of Pharmacology Training Program [NIH 5-T32-GM007040] FX This work was supported by US National Institutes of Health grant R01DA27170 (B.L.R., M.F.S. and W.K.K.) and UO1MH104974 (B.L.R., W.K.K., M.F.S. and K.L.), the US National Institute of Mental Health Psychoactive Drug Screening Program (B.L.R., M.F.S., W.K.K. and X.-P.H.) and the Michael Hooker Distinguished Professorship (B.L.R.). K.L. was supported by the University of North Carolina Department of Pharmacology Training Program (NIH 5-T32-GM007040). The authors thank R. Stevens and S. Katrich for allowing us to use and modify their GPCRome tree (Fig. 6) from ref. 49. We thank R. Axel (Columbia University) for providing HTLA cells. NR 50 TC 26 Z9 26 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 EI 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAY PY 2015 VL 22 IS 5 BP 362 EP U28 DI 10.1038/nsmb.3014 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CH5SD UT WOS:000354094700008 PM 25895059 ER PT J AU Gonzalez, I Munita, R Agirre, E Dittmer, TA Gysling, K Misteli, T Luco, RF AF Gonzalez, Inma Munita, Roberto Agirre, Eneritz Dittmer, Travis A. Gysling, Katia Misteli, Tom Luco, Reini F. TI A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID LONG NONCODING RNA; HISTONE H3; TRIMETHYLATION; TRANSCRIPTION; EXPRESSION; COMPLEXES AB Alternative pre-mRNA splicing is a highly cell type-specific process essential to generating protein diversity. However, the mechanisms responsible for the establishment and maintenance of heritable cell-specific alternative-splicing programs are poorly understood. Recent observations point to a role of histone modifications in the regulation of alternative splicing. Here we report a new mechanism of chromatin-mediated splicing control involving a long noncoding RNA (lncRNA). We have identified an evolutionarily conserved nuclear antisense lncRNA, generated from within the human FGFR2 locus, that promotes epithelial-specific alternative splicing of FGFR2. The lncRNA acts through recruitment of Polycomb-group proteins and the histone demethylase KDM2a to create a chromatin environment that impairs binding of a repressive chromatin-splicing adaptor complex important for mesenchymal-specific splicing. Our results uncover a new function for lncRNAs in the establishment and maintenance of cell-specific alternative splicing via modulation of chromatin signatures. C1 [Gonzalez, Inma; Agirre, Eneritz; Luco, Reini F.] CNRS, Inst Human Genet, ATIP AVENIR Team, UPR 1142, Montpellier, France. [Munita, Roberto; Gysling, Katia] Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago, Chile. [Dittmer, Travis A.; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. RP Luco, RF (reprint author), CNRS, Inst Human Genet, ATIP AVENIR Team, UPR 1142, Montpellier, France. EM mistelit@mail.nih.gov; reini.luco@igh.cnrs.fr FU Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research; French Fondation de la Recherche Medical starting grant [AJE201132]; Fondation ARC pour la Recherche sur le Cancer under the program ATIP-AVENIR; European EpiGeneSys network of excellence; Chilean Millennium Science Initiative grant [P10/063-F] FX We thank V.J. Bardwell (University of Minnesota), R. Carstens (University of Pennsylvania), C.S. Duckett (University of Michigan), M. Garcia-Blanco (Duke University), K. Helin (Biotech Research and Innovation Centre, University of Copenhagen), H. Kimura (Osaka University), H. Koseki (RIKEN Center for Integrative Medical Sciences), R. Klose (Oxford University), D. Reinberg (New York University School of Medicine), K. Tominaga (Jichi Medical School) and D. Haber (Massachusetts General Hospital) for reagents; A. Farcas (R. Klose laboratory) for developing the anti-KDM2b antibody; S. Martinez (R.F.L. laboratory) for establishing the epithelial-to-mesenchymal-transition system; and P. Scaffidi, N. Rascovan, K. Meaburn and R. Klose for discussions and critical reading of the manuscript. This work was supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research (T.M., R.F.L. and T.A.D.), the French Fondation de la Recherche Medical starting grant AJE201132 (R.F.L., I.G. and E.A.), the Fondation ARC pour la Recherche sur le Cancer under the program ATIP-AVENIR (I.G.), the European EpiGeneSys network of excellence (E.A.) and the Chilean Millennium Science Initiative grant P10/063-F (R.M. and K.G.). NR 34 TC 33 Z9 35 U1 5 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 EI 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAY PY 2015 VL 22 IS 5 BP 370 EP U111 DI 10.1038/nsmb.3005 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CH5SD UT WOS:000354094700009 PM 25849144 ER PT J AU Basselin, M Ramadan, E Chen, M Rapoport, SI AF Basselin, Mireille Ramadan, Epolia Chen, Mei Rapoport, Stanley I. TI Anti-Inflammatory Effects of Chronic Aspirin on Brain Arachidonic Acid Metabolites (Retraction of vol 36, pg 139, 2011) SO NEUROCHEMICAL RESEARCH LA English DT Correction C1 [Basselin, Mireille; Ramadan, Epolia; Chen, Mei; Rapoport, Stanley I.] NIA, NIH, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. RP Ramadan, E (reprint author), NIA, NIH, Brain Physiol & Metab Sect, Bldg 9,Room 1S126,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ramadanir@mail.nih.gov NR 1 TC 0 Z9 0 U1 2 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 EI 1573-6903 J9 NEUROCHEM RES JI Neurochem. Res. PD MAY PY 2015 VL 40 IS 5 BP 1094 EP 1094 DI 10.1007/s11064-015-1583-4 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CH5SH UT WOS:000354095100023 ER PT J AU Zhu, J Qu, YQ Ma, T Li, R Du, YZ Huang, SH Shung, KK Zhou, QF Chen, ZP AF Zhu, Jiang Qu, Yueqiao Ma, Teng Li, Rui Du, Yongzhao Huang, Shenghai Shung, K. Kirk Zhou, Qifa Chen, Zhongping TI Imaging and characterizing shear wave and shear modulus under orthogonal acoustic radiation force excitation using OCT Doppler variance method SO OPTICS LETTERS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; IN-VIVO; ELASTOGRAPHY; TISSUE; ULTRASOUND; STRAIN AB We report on a novel acoustic radiation force orthogonal excitation optical coherence elastography (ARFOE-OCE) technique for imaging shear wave and quantifying shear modulus under orthogonal acoustic radiation force (ARF) excitation using the optical coherence tomography (OCT) Doppler variance method. The ARF perpendicular to the OCT beam is produced by a remote ultrasonic transducer. A shear wave induced by ARF excitation propagates parallel to the OCT beam. The OCT Doppler variance method, which is sensitive to the transverse vibration, is used to measure the ARF-induced vibration. For analysis of the shear modulus, the Doppler variance method is utilized to visualize shear wave propagation instead of Doppler OCT method, and the propagation velocity of the shear wave is measured at different depths of one location with the M scan. In order to quantify shear modulus beyond the OCT imaging depth, we move ARF to a deeper layer at a known step and measure the time delay of the shear wave propagating to the same OCT imaging depth. We also quantitatively map the shear modulus of a cross-section in a tissue-equivalent phantom after employing the B scan. (C) 2015 Optical Society of America C1 [Zhu, Jiang; Qu, Yueqiao; Li, Rui; Du, Yongzhao; Huang, Shenghai; Chen, Zhongping] Univ Calif Irvine, Beckman Laser Inst, Irvine, CA 92612 USA. [Qu, Yueqiao; Chen, Zhongping] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92697 USA. [Ma, Teng; Shung, K. Kirk; Zhou, Qifa] Univ So Calif, Ultrason Transducer Resource Ctr, Dept Biomed Engn, NIH, Los Angeles, CA 90089 USA. RP Chen, ZP (reprint author), Univ Calif Irvine, Beckman Laser Inst, 1002 Hlth Sci Rd East, Irvine, CA 92612 USA. EM z2chen@uci.edu RI Zhu, Jiang/O-4869-2016 OI Zhu, Jiang/0000-0002-2601-4967 FU National Institutes of Health [R01EB-10090, R01HL-125084, R01HL-105215, R01EY-021529, P41-EB002182, P41-EB015890] FX This work was supported by the National Institutes of Health under grants R01EB-10090, R01HL-125084, R01HL-105215, R01EY-021529, P41-EB002182, P41-EB015890. Dr. Zhongping Chen has a financial interest in OCT Medical Inc, which, however, did not support this work. NR 20 TC 5 Z9 6 U1 0 U2 9 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD MAY 1 PY 2015 VL 40 IS 9 BP 2099 EP 2102 DI 10.1364/OL.40.002099 PG 4 WC Optics SC Optics GA CH3IQ UT WOS:000353924600056 PM 25927794 ER PT J AU Wang, EA McGinms, KA Goulet, J Bryant, K Gibert, C Leaf, DA Mattocks, K Fiellin, LE Vogenthaler, N Justice, AC Fiellin, DA AF Wang, Emily A. McGinms, Kathleen A. Goulet, Joseph Bryant, Kendall Gibert, Cynthia Leaf, David A. Mattocks, Kristin Fiellin, Lynn E. Vogenthaler, Nicholas Justice, Amy C. Fiellin, David A. CA Vet Aging Cohort Study Project Tea TI Food Insecurity and Health: Data from the Veterans Aging Cohort Study SO PUBLIC HEALTH REPORTS LA English DT Article ID HIV-INFECTED INDIVIDUALS; MENTAL-HEALTH; HOUSING INSTABILITY; WELFARE RECIPIENTS; INSUFFICIENCY; CARE; MORTALITY; ADULTS; CHILDREN; DISEASE AB Objective. Food insecurity may be a modifiable and independent risk factor for worse control of medical conditions, but it has not been explored among veterans. We determined the prevalence of, and factors independently associated with, food insecurity among veterans in the Veterans Aging Cohort Study (VACS). Methods. Using data from VACS from 2002-2008, we determined the prevalence of food insecurity among veterans who have accessed health care in the Veterans Health Administration (VA) as defined by "concern about having enough food for you or your family in the past month." We used multivariable logistic regression to determine factors independently associated with food insecurity and tests of trend to measure the association between food insecurity and control of hypertension, diabetes, HIV, and depression. Results. Of the 6,709 veterans enrolled in VACS, 1,624 (24%) reported being food insecure. Food insecurity was independently associated with being African American, earning <$25,000/year, recent homelessness, marijuana use, and depression. Being food insecure was also associated with worse control of hypertension, diabetes, HIV and depression (p<0.001). Conclusion. Food insecurity is prevalent and associated with worse control of medical conditions among veterans who have accessed care in the VA. C1 [Wang, Emily A.; Goulet, Joseph; Fiellin, Lynn E.; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [McGinms, Kathleen A.; Goulet, Joseph; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Bryant, Kendall] NIAAA, NIH, Rockville, MD 20852 USA. [Gibert, Cynthia] VA Med Ctr, Washington, DC USA. [Gibert, Cynthia] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Leaf, David A.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Mattocks, Kristin] VA Cent Western Massachusetts, Northampton, MA USA. [Mattocks, Kristin] Univ Massachusetts, Sch Med, Worcester, MA USA. [Vogenthaler, Nicholas] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Publ Hlth, Ctr Interdisciplinary Res AIDS, New Haven, CT 06510 USA. RP Wang, EA (reprint author), Yale Univ, Sch Med, Gen Internal Med, Harkness Hall Bldg A,367 Cedar St,Ste 410A, New Haven, CT 06510 USA. EM emily.wang@yale.edu OI Fiellin, David/0000-0002-4006-010X; Goulet, Joseph/0000-0002-0842-804X FU National Institute on Alcohol Abuse and Alcoholism [U01-AA-13566, U10-AA-13566]; National Institute on Aging (NIA) [K23-AG00826]; Robert Wood Johnson Generalist Faculty Scholar Award; NIA, National Institute of Mental Health; Veterans Health Administration Health Services Research & Development Research Enhancement Award Program (REAP) PRIME Project [REA-08-266]; National Heart, Lung, and Blood Institute [K23-HL103720]; Yale Clinical Center of Investigation's Clinical & Translations Science Awards Grant [UL1 RR024139] FX The sponsor 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. The Veterans Aging Cohort Study (VACS) is funded by the National Institute on Alcohol Abuse and Alcoholism (#U01-AA-13566 and #U10-AA-13566); the National Institute on Aging (NIA) (#K23-AG00826); and the Robert Wood Johnson Generalist Faculty Scholar Award, an interagency agreement among the NIA, National Institute of Mental Health, and Veterans Health Administration Health Services Research & Development Research Enhancement Award Program (REAP) PRIME Project (#REA-08-266). Emily Wang receives salary support from a career development award from the National Heart, Lung, and Blood Institute (#K23-HL103720) and the Yale Clinical Center of Investigation's Clinical & Translations Science Awards Grant (#UL1 RR024139). The Institutional Review Boards at the Veterans Health Administrations in Atlanta, Georgia; Baltimore, Maryland; Bronx, New York; Manhattan/Brooklyn, New York; Houston, Texas; Los Angeles, California; Pittsburgh, Pennsylvania; and Washington, D.C., approved the study, and all participants provided written informed consent prior to enrollment. NR 33 TC 7 Z9 7 U1 3 U2 11 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 2015 VL 130 IS 3 BP 261 EP 268 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CH5JJ UT WOS:000354071600013 PM 25931630 ER PT J AU Bataller, R Gao, B AF Bataller, Ramon Gao, Bin TI Liver Fibrosis in Alcoholic Liver Disease SO SEMINARS IN LIVER DISEASE LA English DT Review DE alcoholic hepatitis; hepatic stellate cells; steatohepatitis; animal models ID INDUCED HEPATIC-FIBROSIS; HEPATOCELLULAR-CARCINOMA; NONALCOHOLIC STEATOHEPATITIS; GENETIC POLYMORPHISMS; STELLATE CELLS; UNITED-STATES; RISK-FACTORS; CIRRHOSIS; INJURY; METAANALYSIS AB Excessive alcohol consumption causes a wide spectrum of liver disease, ranging from simple steatosis to severe forms of liver injury such as steatohepatitis, liver fibrosis, cirrhosis, and liver cancer. Moreover, alcohol consumption also accelerates liver fibrosis in patients with other types of liver diseases such as viral hepatitis and nonalcoholic fatty liver disease. Virtually all clinical complications of alcoholic liver disease occur in patients with established fibrosis and cirrhosis, thus making fibrosis a key parameter for treatment and prognosis of patients. Here, the authors review diagnosis, management, and antifibrotic therapy of alcoholic liver fibrosis. They discuss both the unique features of alcoholic liver fibrosis and the similarities to liver fibrosis from other etiologies, and review molecular pathogenesis and animal models. Finally, future directions for basic and clinical research on alcoholic liver fibrosis are proposed. C1 [Bataller, Ramon] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC 27599 USA. [Gao, Bin] NIAAA, Lab Liver Dis, Natl Inst Hlth, Bethesda, MD USA. RP Bataller, R (reprint author), Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC 27599 USA. EM ramon_bataller@med.unc.edu NR 102 TC 16 Z9 16 U1 3 U2 17 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 EI 1098-8971 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD MAY PY 2015 VL 35 IS 2 BP 146 EP 156 DI 10.1055/s-0035-1550054 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CH9PM UT WOS:000354368100006 PM 25974900 ER PT J AU Liu, WL Zhang, K Locatis, C Ackerman, M AF Liu, Wei-Li Zhang, Kai Locatis, Craig Ackerman, Michael TI Cloud and Traditional Videoconferencing Technology for Telemedicine and Distance Learning SO TELEMEDICINE AND E-HEALTH LA English DT Article DE telecommunications; distance learning; cloud computing; technology; telemedicine AB Introduction: Cloud-based videoconferencing versus traditional systems are described for possible use in telemedicine and distance learning. Materials and Methods: Differences between traditional and cloud-based videoconferencing systems are examined, and the methods for identifying and testing systems are explained. Findings are presented characterizing the cloud conferencing genre and its attributes versus traditional H.323 conferencing. Results: Because the technology is rapidly evolving and needs to be evaluated in reference to local needs, it is strongly recommended that this or other reviews not be considered substitutes for personal hands-on experience. Conclusions: This review identifies key attributes of the technology that can be used to appraise the relevance of cloud conferencing technology and to determine whether migration from traditional technology to a cloud environment is warranted. An evaluation template is provided for assessing systems appropriateness. C1 [Liu, Wei-Li; Zhang, Kai; Locatis, Craig; Ackerman, Michael] Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD 20894 USA. RP Liu, WL (reprint author), Natl Lib Med, Off High Performance Comp & Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM wliu@mail.nih.gov FU National Institutes of Health/National Library of Medicine intramural research program FX This review was supported by the National Institutes of Health/National Library of Medicine intramural research program. The authors acknowledge the contributions of Willis Nguyen, a student intern who helped install and test the programs. NR 9 TC 1 Z9 1 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD MAY 1 PY 2015 VL 21 IS 5 BP 422 EP 426 DI 10.1089/tmj.2014.0121 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CH5UA UT WOS:000354099600011 PM 25785761 ER PT J AU Zeng, PB Ma, LL Gao, Z Wang, JX Liu, J Huang, XW Yang, QZ Cao, R Wen, XQ Zhu, LL Ma, HL Yang, ZD Lee, TH Brambilla, D Yuan, M Glynn, S Ness, P Kleinman, S Busch, M Shan, H AF Zeng, Peibin Ma, Lili Gao, Zhan Wang, Jingxing Liu, Jing Huang, Xianwei Yang, Qizhi Cao, Ruan Wen, Xiuqiong Zhu, Lili Ma, Hongli Yang, Zhendong Lee, Tzong-Hae Brambilla, Donald Yuan, Michelle Glynn, Simone Ness, Paul Kleinman, Steve Busch, Michael Shan, Hua CA Int Component NHLBI Recipient TI A study of seroprevalence and rates of asymptomatic viremia of severe fever with thrombocytopenia syndrome virus among Chinese blood donors SO TRANSFUSION LA English DT Article ID SHANDONG PROVINCE; INFECTION; BUNYAVIRUS; ASSAY; TRANSMISSION; ANTIBODIES; CONTACT AB BackgroundSevere fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne pathogen that can cause fatal severe fever with thrombocytopenia syndrome, was first identified in China in 2009. Limited evidence suggests that SFTSV can be transmitted between humans via blood contact, raising concerns over transfusion safety. A study of donor samples from three Chinese blood centers was conducted to investigate the seroprevalence and rate of SFTSV viremia among Chinese blood donors. Study Design and MethodsFrom April 16 to October 31, 2012, a total of 17,208 plasma samples were collected from donors at Xinyang (located in an SFTSV-endemic area), Mianyang, and Luoyang Blood Centers. Assessment of anti-SFTSV total antibody was performed on all samples using enzyme-linked immunosorbent assay. Repeat-reactive samples were tested for SFTSV RNA using reverse transcription (RT)-real-time polymerase chain reaction (PCR) assay with Taqman probes. In addition, 9960 of the Xinyang samples were tested in pools of 4 by the same PCR method and each of the samples in a reactive pool was tested individually. ResultsDonor seroreactivity rates were as follows: Xinyang, 0.54% (80/14,752); Mianyang, 0.27% (3/1130); and Luoyang, 0.28% (3/1326). All seroreactive samples were negative on RT-PCR single-sample testing. Two RT-PCR-reactive donor samples were identified, both with estimated viral loadof less than20plaque-forming units/mL. The RNA prevalence rate for SFTSV among donors in Xinyang was 0.02%. ConclusionThis was the first multiregion study of SFTSV sero- and viral prevalence among Chinese blood donors. Viral prevalence was low and no seroreactive sample was viremic, suggesting a limited impact of SFTSV on blood safety in China. C1 [Zeng, Peibin; Ma, Lili; Gao, Zhan; Wang, Jingxing] Chinese Acad Med Sci, Inst Blood Transfus, Chengdu 610052, Sichuan, Peoples R China. [Liu, Jing; Ness, Paul; Shan, Hua] Johns Hopkins Univ Hosp, Dept Transfus Med, Baltimore, MD 21287 USA. [Huang, Xianwei; Yang, Qizhi] Xinyang Blood Ctr, Xinyang, Peoples R China. [Cao, Ruan; Wen, Xiuqiong] Mianyang Blood Ctr, Mianyang, Peoples R China. [Zhu, Lili; Ma, Hongli] Luoyang Blood Ctr, Luoyang, Peoples R China. [Yang, Zhendong; Busch, Michael] Xinyang 154 Mil Hosp, Xinyang, Peoples R China. [Lee, Tzong-Hae] Blood Syst Res Inst, San Francisco, CA USA. [Brambilla, Donald; Yuan, Michelle] RTI Int, Rockville, MD USA. [Glynn, Simone] NHLBI, Bethesda, MD 20892 USA. [Kleinman, Steve] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Zeng, PB (reprint author), Chinese Acad Med Sci, Inst Blood Transfus, Chengdu 610052, Sichuan, Peoples R China. EM zengpeibin@live.cn FU NHLBI Recipient Epidemiology and Donor Evaluation Study-III [X101222002] FX This work was supported by the NHLBI Recipient Epidemiology and Donor Evaluation Study-III (X101222002). NR 24 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD MAY PY 2015 VL 55 IS 5 BP 965 EP 971 DI 10.1111/trf.12953 PG 7 WC Hematology SC Hematology GA CH8JB UT WOS:000354281500009 PM 25496479 ER PT J AU Custer, B Kessler, D Vahidnia, F Leparc, G Krysztof, DE Shaz, B Kamel, H Glynn, S Dodd, RY Stramer, SL AF Custer, Brian Kessler, Debra Vahidnia, Farnaz Leparc, German Krysztof, David E. Shaz, Beth Kamel, Hany Glynn, Simone Dodd, Roger Y. Stramer, Susan L. CA NHLBI Retrovirus Epidemiology TI Risk factors for retrovirus and hepatitis virus infections in accepted blood donors SO TRANSFUSION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; B-VIRUS; UNITED-STATES; RESIDUAL RISK; BEHAVIORAL-CHARACTERISTICS; NATIONAL-HEALTH; PREVALENCE; EPIDEMIOLOGY; DONATION; EXPERIENCE AB BackgroundRisk factor surveillance among infected blood donors provides information on the effectiveness of eligibility assessment and is critical for reducing risk of transfusion-transmitted infection. Study Design and MethodsAmerican Red Cross, Blood Systems, Inc., New York Blood Center, and OneBlood participated in a case-control study from 2010 to 2013. Donors with serologic and nucleic acid testing (NAT) or NAT-only confirmed human immunodeficiency virus (HIV), hepatitisB virus (HBV), hepatitisC virus (HCV), or serology-confirmed human T-lymphotropic virus (HTLV) infections (cases) and donors with false-positive results (controls) were interviewed for putative behavioral and demographic risks. Frequencies and adjusted odds ratios (AORs) from multivariable logistic regression analyses for each exposure in cases compared to controls are reported. ResultsIn the study, 196 HIV, 292 HBV, 316 HCV, and 198 HTLV cases, and 1587 controls were interviewed. For HIV, sex with an HIV+ person (AOR, 132; 95% confidence interval [CI], 27-650) and male-male sex (AOR, 62; 95% CI, 27-140) were primary risk factors. For HBV, first-time donor status (AOR, 16; 95% CI, 10-27), sex with an injection drug user (IDU; AOR, 11; 95% CI, 5-28), and black race (AOR, 11; 95% CI, 6-19) were primary. For HCV, IDU (AOR, 42; 95% CI, 13-136), first time (AOR, 18; 95% CI, 10-30), and a family member with hepatitis (AOR, 15; 95% CI, 6-40) were primary. For HTLV, sex with an IDU (AOR, 22; 95% CI, 10-48), 55 years old or more (AOR, 21; 95% CI, 8-52], and first time (AOR, 15; 95% CI, 9-24) were primary. ConclusionsDespite education efforts and risk screening, individuals with deferrable risks still donate; they may fail to understand or ignore or do not believe they have risk. Recipients have potential transfusion-transmitted infection risk because of nondisclosure by donors. C1 [Custer, Brian; Vahidnia, Farnaz] Blood Syst Res Inst, San Francisco, CA 94118 USA. [Custer, Brian] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Kessler, Debra; Shaz, Beth] New York Blood Ctr, New York, NY 10021 USA. [Leparc, German] OneBlood, Tampa, FL USA. [Krysztof, David E.; Stramer, Susan L.] Amer Red Cross, Sci Support Off, Gaithersburg, MD USA. [Kamel, Hany] Blood Syst Inc, Scottsdale, AZ USA. [Glynn, Simone] NHLBI, NIH, Rockville, MD USA. [Dodd, Roger Y.] Amer Red Cross, Holland Lab, Rockville, MD USA. RP Custer, B (reprint author), Blood Syst Res Inst, 270 Masonic Ave, San Francisco, CA 94118 USA. EM bcuster@bloodsystems.org OI Vahidnia, Farnaz/0000-0003-1130-4643 FU Retrovirus Epidemiology Donor Study-II (REDS-II) - National Heart, Lung and Blood Institute, National Institutes of Health [HHSN26820041717] FX This study was funded by research contract HHSN26820041717 from the Retrovirus Epidemiology Donor Study-II (REDS-II) sponsored by the National Heart, Lung and Blood Institute, National Institutes of Health. NR 37 TC 13 Z9 13 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD MAY PY 2015 VL 55 IS 5 BP 1098 EP 1107 DI 10.1111/trf.12951 PG 10 WC Hematology SC Hematology GA CH8JB UT WOS:000354281500027 PM 25470984 ER PT J AU Hall, EC Engels, EA Pfeiffer, RM Segev, DL AF Hall, Erin C. Engels, Eric A. Pfeiffer, Ruth M. Segev, Dorry L. TI Association of Antibody Induction Immunosuppression With Cancer After Kidney Transplantation SO TRANSPLANTATION LA English DT Article ID POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER; NON-HODGKIN-LYMPHOMA; UNITED-STATES; RENAL-TRANSPLANTATION; DEPLETIONAL INDUCTION; RISK-FACTORS; RECIPIENTS; EPIDEMIOLOGY; ALEMTUZUMAB; SEROSTATUS AB Background. Induction immunosuppression is a main stay of rejection prevention after transplantation. Studies have suggested a connection between antibody induction agents and cancer development, potentially limiting important immunosuppression protocols. Methods. We used a linkage of U.S. transplantation data and cancer registries to explore the relationship between induction and cancer after transplantation. A total of 111,857 kidney recipients (1987-2009) in the Transplant Cancer Match Study, which links the Scientific Registry for Transplant Recipients and U.S. Cancer Registries, were included. Poisson regression models were used to estimate adjusted incidence rate ratios (aIRR) of non-Hodgkin lymphoma (NHL) and other cancers with increased incidence after transplantation (lung, colorectal, kidney, and thyroid cancers, plus melanoma). Results. Two thousand seven hundred sixty-three cancers of interest were identified. Muromonab-CD3 was associated with increased NHL (aIRR, 1.37; 95% CI, 1.06-1.76). Alemtuzumab was associated with increased NHL (aIRR, 1.79; 95% CI, 1.02-3.14), colorectal cancer (aIRR, 2.46; 95% CI, 1.03-5.91), and thyroid cancer (aIRR, 3.37; 95% CI, 1.55-7.33). Polyclonal induction was associated with increased melanoma (aIRR, 1.50; 95% CI, 1.06-2.14). Conclusion. Our findings highlight the relative safety with regard to cancer risk of themost common induction therapies, the need for surveillance of patients treated with alemtuzumab, and the possible role for increased melanoma screening for those patients treated with polyclonal anti-T-cell induction. C1 [Hall, Erin C.; Segev, Dorry L.] Johns Hopkins Sch Med, Dept Surg, Baltimore, MD USA. [Hall, Erin C.; Engels, Eric A.; Pfeiffer, Ruth M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Segev, Dorry L.] Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Segev, DL (reprint author), Johns Hopkins Med Inst, Transplant Surg, 720 Rutland Ave,Ross 771B, Baltimore, MD 21205 USA. EM dorry@jhmi.edu FU National Cancer Institute; National Institute of Health; Sanofi Pharmaceuticals; Arbor Research Collaborative for Health in Ann Arbor, MI [HHSH234200537009C]; National Program of Cancer Registries ofthe Centers for Disease Control and Prevention: California [1U58 DP000807-01]; National Program of Cancer Registries ofthe Centers for Disease Control and Prevention: Colorado [U58 DP000848-04]; National Program of Cancer Registries ofthe Centers for Disease Control and Prevention: Georgia [5U58DP000817-05]; National Program of Cancer Registries ofthe Centers for Disease Control and Prevention: Illinois [5658DP000805-04]; National Program of Cancer Registries ofthe Centers for Disease Control and Prevention: Michigan [5U58DP000812-03]; National Program of Cancer Registries ofthe Centers for Disease Control and Prevention: New Jersey [5U58/DP000808-05]; National Program of Cancer Registries ofthe Centers for Disease Control and Prevention: New York [150351]; National Program of Cancer Registries ofthe Centers for Disease Control and Prevention: North Carolina [U58DP000832]; National Program of Cancer Registries ofthe Centers for Disease Control and Prevention: Texas [5U58DP000824-04]; National Cancer Institute: California [HHSN261201000036C, HHSN261201000035C, HHSN261201000034C]; National Cancer Institute: Connecticut [HHSN261201000024C]; National Cancer Institute: Hawaii [HHSN261201000037C, N01-PC-35137, N01-PC-35139]; National Cancer Institute: Iowa [N01-PC-35143]; National Cancer Institute: New Jersey [HHSN261201000027C N01-PC-54405]; National Cancer Institute: Seattle-Puget Sound [N01-PC-35142]; National Cancer Institute: Utah [HHSN261201000026C]; state of California; state of Colorado; state of Connecticut; state of Illinois; state of Iowa; state of New Jersey; state of New York (Cancer Surveillance Improvement Initiative) [14-2491]; state of Texas; state of Washington; Fred Hutchinson Cancer Research Center in Seattle, WA FX E.A.E. and R.M.P. were supported by Intramural Research Program (National Cancer Institute). E.C.H. was supported by a National Institute of Health training grant. D.L.S. was supported by Sanofi Pharmaceuticals (Investigator-Initiated Grant).; During the initial period when registry linkages were performed, the SRTR was managed by Arbor Research Collaborative for Health in Ann Arbor, MI (contract HHSH234200537009C); beginning in September 2010, the SRTR was managed by Minneapolis Medical Research Foundation in Minneapolis, MN (HHSH250201000018C). The following cancer registries were supported by the National Program of Cancer Registries ofthe Centers for Disease Control and Prevention: California (agreement 1U58 DP000807-01), Colorado (U58 DP000848-04), Georgia (5U58DP000817-05), Illinois (5658DP000805-04), Michigan (5U58DP000812-03), New Jersey (5U58/DP000808-05), New York (150351), North Carolina (U58DP000832), and Texas (5U58DP000824-04). The following cancer registries were supported by the SEER Program of the National Cancer Institute: California (contracts HHSN261201000036C, HHSN261201000035C, and HHSN261201000034C), Connecticut (HHSN261201000024C), Hawaii (HHSN261201000037C, N01-PC-35137, and N01-PC-35139), Iowa (N01-PC-35143), New Jersey (HHSN261201000027C N01-PC-54405), Seattle-Puget Sound (N01-PC-35142), and Utah (HHSN261201000026C). Additional support was provided by the states of California, Colorado, Connecticut, Illinois, Iowa, New Jersey, New York (Cancer Surveillance Improvement Initiative 14-2491), Texas, and Washington, as well as the Fred Hutchinson Cancer Research Center in Seattle, WA. NR 28 TC 9 Z9 11 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD MAY PY 2015 VL 99 IS 5 BP 1051 EP 1057 DI 10.1097/TP.0000000000000449 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA CH3WW UT WOS:000353962700032 PM 25340595 ER PT J AU Sanchez-Martin, D Sorensen, MD Lykkemark, S Sanz, L Kristensen, P Ruoslahti, E Alvarez-Vallina, L AF Sanchez-Martin, David Sorensen, Morten Draeby Lykkemark, Simon Sanz, Laura Kristensen, Peter Ruoslahti, Erkki Alvarez-Vallina, Luis TI Selection strategies for anticancer antibody discovery: searching off the beaten path SO TRENDS IN BIOTECHNOLOGY LA English DT Review DE therapeutic antibodies; tumor-associated antigens; phage display; advanced phage selections ID PHAGE DISPLAY LIBRARY; SINGLE-CHAIN FV; LASER CAPTURE MICRODISSECTION; CELL-SURFACE ANTIGENS; IN-VIVO SELECTION; CANCER CELLS; TUMOR-ANTIGENS; COLORECTAL-CANCER; PERIPHERAL-BLOOD; HETEROGENEOUS POPULATION AB Antibody-based drugs represent one of the most successful and promising therapeutic approaches in oncology. Large combinatorial phage antibody libraries are available for the identification of therapeutic antibodies and various technologies exist for their further conversion into multivalent and multispecific formats optimized for the desired pharmacokinetics and the pathological context. However, there is no technology for antigen profiling of intact tumors to identify tumor markers targetable with antibodies. Such constraints have led to a relative paucity of tumor-associated antigens for antibody targeting in oncology. Here we review novel approaches aimed at the identification of antibody-targetable, accessible antigens in intact tumors. We hope that such advanced selection approaches will be useful in the development of next-generation antibody therapies for cancer. C1 [Sanchez-Martin, David] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sorensen, Morten Draeby] Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain. [Sorensen, Morten Draeby] Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus C, Denmark. [Lykkemark, Simon] Aarhus Univ, Dept Clin Med, DK-8000 Aarhus C, Denmark. [Lykkemark, Simon] Aarhus Univ, Sinodanish Ctr, DK-8000 Aarhus C, Denmark. [Sanz, Laura; Alvarez-Vallina, Luis] Hosp Univ Puerta Hierro, Mol Immunol Unit, Madrid 28222, Majadahonda, Spain. [Kristensen, Peter; Alvarez-Vallina, Luis] Aarhus Univ, Dept Engn, DK-8000 Aarhus C, Denmark. [Ruoslahti, Erkki] Sanford Burnham Med Res Inst, Ctr Canc, La Jolla, CA 92037 USA. [Ruoslahti, Erkki] Univ Calif Santa Barbara, Ctr Nanomed, Santa Barbara, CA 93106 USA. [Alvarez-Vallina, Luis] Univ Calif Santa Barbara, Dept Cell Mol & Dev Biol, Santa Barbara, CA 93106 USA. RP Alvarez-Vallina, L (reprint author), Hosp Univ Puerta Hierro, Mol Immunol Unit, Madrid 28222, Majadahonda, Spain. EM lav@eng.au.dk RI Sanz, Laura/F-8542-2010; Sanchez-Martin, David/C-9927-2013; OI Sanz, Laura/0000-0002-3119-3218; Sanchez-Martin, David/0000-0002-2712-4762; Kristensen, Peter/0000-0001-7205-6853; Lykkemark, Simon/0000-0001-8920-6926 FU Ministerio de Economia y Competitividad [BIO2011-22738]; Novo Nordisk Foundation [11019]; National Cancer Institute; Fondo de Investigacion Snitaria/Instituto de Salud Carlos III [PI13/00090]; Comunidad de Madrid [S2010/BMD-2312]; Danish Cancer Society; Lundbeck Foundation [R126-2012-12143]; Danish Council for Independent Research - Technology and Production Sciences [09-065063, 0602-02377B]; Danish Cancer Society [R40-A2115] FX L.A-V. was supported by grants from the Ministerio de Economia y Competitividad (BIO2011-22738) and the Novo Nordisk Foundation (11019). E.R. was supported by grants from the National Cancer Institute. L.S. was supported by grants from the Fondo de Investigacion Snitaria/Instituto de Salud Carlos III (PI13/00090) and the Comunidad de Madrid (S2010/BMD-2312). M.D.S. was supported by a grant from the Danish Cancer Society. P.K. was supported by grants from the Lundbeck Foundation (R126-2012-12143), the Danish Council for Independent Research - Technology and Production Sciences (09-065063 and 0602-02377B), and the Danish Cancer Society (R40-A2115). NR 90 TC 5 Z9 5 U1 2 U2 15 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD MAY PY 2015 VL 33 IS 5 BP 292 EP 301 DI 10.1016/j.tibtech.2015.02.008 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CH6PG UT WOS:000354157900007 PM 25819764 ER PT J AU Lee, PC Rietsch, A AF Lee, Pei-Chung Rietsch, Arne TI Fueling type III secretion SO TRENDS IN MICROBIOLOGY LA English DT Review DE T3SS; needle complex; flagellum; proton motive force; ATPase ID PROTON MOTIVE FORCE; YERSINIA-ENTEROCOLITICA; FLAGELLAR FILAMENTS; EXPORT APPARATUS; PROTEIN EXPORT; ANGSTROM RESOLUTION; ESCHERICHIA-COLI; FLII ATPASE; SYSTEM; TRANSLOCATION AB Type Ill secretion systems (T3SSs) are complex nanomachines that export proteins from the bacterial cytoplasm across the cell envelope in a single step. They are at the core of the machinery used to assemble the bacterial flagellum, and the needle complex many Gram-negative pathogens use to inject effector proteins into host cells and cause disease. Several models have been put forward to explain how this export is energized, and the mechanism has been the subject of considerable debate. Here we present an overview of these models and discuss their relative merits. Recent evidence suggests that the proton motive force (pmf) is the primary energy source for type Ill secretion, although contribution from refolding of secreted proteins has not been ruled out. The mechanism by which the pmf is converted to protein export remains enigmatic. C1 [Lee, Pei-Chung] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. [Rietsch, Arne] Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA. RP Rietsch, A (reprint author), Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA. EM arne.rietsch@case.edu OI Rietsch, Arne/0000-0002-1556-7064 FU NIAID NIH HHS [R21 AI107131] NR 40 TC 9 Z9 9 U1 0 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-842X EI 1878-4380 J9 TRENDS MICROBIOL JI Trends Microbiol. PD MAY PY 2015 VL 23 IS 5 BP 296 EP 300 DI 10.1016/j.tim.2015.01.012 PG 5 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA CH6MS UT WOS:000354151300009 PM 25701111 ER PT J AU Spagnolo, PA Colloca, L Heilig, M AF Spagnolo, Primavera A. Colloca, Luana Heilig, Markus TI The Role of Expectation in the Therapeutic Outcomes of Alcohol and Drug Addiction Treatments SO ALCOHOL AND ALCOHOLISM LA English DT Article ID SUBSTANCE-ABUSE TREATMENT; PLACEBO; REWARD; ATTITUDES; ADOPTION AB Throughout history, patient-physician relationships have been acknowledged as an important component of the therapeutic effects of any pharmacological treatment. Here, we discuss the role of physicians' expectations in influencing the therapeutic outcomes of alcohol and drug addiction pharmacological treatments. As largely demonstrated, such expectations and attitudes may contribute to produce placebo and nocebo effects that in turn affect the course of the disease and the response to the therapy. This article is aimed at discussing the current insights into expectations, placebo and nocebo mechanisms and their impact on the therapeutic outcomes of alcohol and drug addiction treatments; with the goal of informing physicians and other health care providers about the potentially widespread implications for clinical practice and for a successful treatment regimen. C1 [Spagnolo, Primavera A.; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. [Colloca, Luana] Univ Maryland, Sch Nursing, Pain & Translat Symptom Sci, Baltimore, MD 21201 USA. [Colloca, Luana] Univ Maryland, UM Ctr Adv Chron Pain Res, Baltimore, MD 21201 USA. [Colloca, Luana] Univ Maryland, Dept Anesthesiol, Sch Med, Baltimore, MD 21201 USA. RP Spagnolo, PA (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, Clin Res Ctr, Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM vera.spagnolo@nih.gov NR 27 TC 0 Z9 0 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 EI 1464-3502 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD MAY-JUN PY 2015 VL 50 IS 3 BP 282 EP 285 DI 10.1093/alcalc/agv015 PG 4 WC Substance Abuse SC Substance Abuse GA CH2AY UT WOS:000353827100004 PM 25761920 ER PT J AU Emadi, A Faramand, R Carter-Cooper, B Tolu, S Ford, LA Lapidus, RG Wetzler, M Wang, ES Etemadi, A Griffiths, EA AF Emadi, Ashkan Faramand, Rawan Carter-Cooper, Brandon Tolu, Seda Ford, Laurie A. Lapidus, Rena G. Wetzler, Meir Wang, Eunice S. Etemadi, Arash Griffiths, Elizabeth A. TI Presence of isocitrate dehydrogenase mutations may predict clinical response to hypomethylating agents in patients with acute myeloid leukemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID MYELODYSPLASTIC SYNDROMES; IDH2 MUTATIONS; OLDER PATIENTS; INTENSIVE CHEMOTHERAPY; DECITABINE; AML; DIFFERENTIATION; THERAPY; ADULTS; AZACITIDINE AB Mutations in IDH1 and IDH2 occur in 15-20% of AML cases, resulting in the production of 2-hydroxyglutarate, which promotes aberrant hypermethylation of DNA in leukemic cells. Although these mutations have been shown to have prognostic implications for patients with AML, optimal treatment strategies have yet to be defined. We retrospectively identified forty-two patients with AML treated with DNA methyltransferase inhibitors (DNMTIs) decitabine (n=36) or azacitidine (n=6) and performed analysis of stored samples for the presence of IDH1 and IDH2 mutations. Of the forty-two samples analyzed, seven (16.7%) had IDH mutations. Thirteen patients (31%) achieved remission [(complete remission (CR)/complete remission with incomplete count recovery (CRi)/partial response (PR)] after treatment with a DNMTI, five of seven (71.4%) with IDH mutations and eight of thirty-five (22.9%) without IDH mutations (P=0.01). When adjusted for age at diagnosis, sex, bone marrow blast percentage and cytogenetic, the odds of achieving response after administration of a DNMTI among patients with an IDH mutation was 14.2 when compared to patients without an IDH mutation (95%CI: 1.3-150.4). IDH1 and IDH2 mutations may predict a favorable response to DNMTI in patients with AML. Am. J. Hematol. 90:E77-E79, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Emadi, Ashkan; Faramand, Rawan; Carter-Cooper, Brandon; Tolu, Seda; Lapidus, Rena G.] Univ Maryland, Sch Med, Dept Internal Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Ford, Laurie A.; Wetzler, Meir; Wang, Eunice S.; Griffiths, Elizabeth A.] SUNY Buffalo, Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14260 USA. [Etemadi, Arash] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Emadi, A (reprint author), Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Leukemia & Hematol Malignancies,Med, 22 South Greene St,Room N9E24, Baltimore, MD 21201 USA. EM aemadi@umm.eduand; elizabeth.griffiths@roswellpark.org RI Etemadi, Arash/C-1386-2016 OI Etemadi, Arash/0000-0002-3458-1072 FU National Cancer Institute [CA 16056]; Emadi Research Foundation Account at University of Maryland Greenebaum Cancer Center (UMGCC); Leonard S. LuVullo Endowment for Leukemia Research; Nancy C. Cully Endowment for Leukemia Research; Babcock Family Endowment; Heidi Leukemia Research Fund, Buffalo, NY; Roswell Park Alliance Foundation; Louis M. Sklarow Memorial Fund FX Contract grant sponsor: National Cancer Institute Grant; Contract grant number: CA 16056.; Contract grant sponsors: Emadi Research Foundation Account at University of Maryland Greenebaum Cancer Center (UMGCC).; Contract grant sponsor: the Leonard S. LuVullo Endowment for Leukemia Research.; Contract grant sponsor: the Nancy C. Cully Endowment for Leukemia Research.; Contract grant sponsor: the Babcock Family Endowment.; Contract grant sponsor: the Heidi Leukemia Research Fund, Buffalo, NY.; Contract grant sponsor: Roswell Park Alliance Foundation; the Louis M. Sklarow Memorial Fund. NR 27 TC 17 Z9 19 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2015 VL 90 IS 5 BP E77 EP E79 DI 10.1002/ajh.23965 PG 3 WC Hematology SC Hematology GA CG6FS UT WOS:000353393300001 PM 25651001 ER PT J AU Jennings, BL Moore, JA Pingili, AK Estes, AM Fang, XR Kanu, A Gonzalez, FJ Malik, KU AF Jennings, Brett L. Moore, Joseph A. Pingili, Ajeeth K. Estes, Anne M. Fang, Xiao R. Kanu, Alie Gonzalez, Frank J. Malik, Kafait U. TI Disruption of the cytochrome P-450 1B1 gene exacerbates renal dysfunction and damage associated with angiotensin II-induced hypertension in female mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE angiotensin II; cytochrome P-450 1B1-deficient female mice; kidney dysfunction; increased oxidative stress; reduced antioxidant activity ID BLOOD-PRESSURE REGULATION; MESSENGER-RNA EXPRESSION; NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE-CELLS; SEX-DIFFERENCES; SUPEROXIDE-PRODUCTION; OXIDATIVE STRESS; MESANGIAL CELLS; PULMONARY-HYPERTENSION; COLLAGEN-SYNTHESIS AB Recently, we demonstrated in female mice that protection against ANG II-induced hypertension and associated cardiovascular changes depend on cytochrome P-450 (CYP) 1B1. The present study was conducted to determine if Cyp1b1 gene disruption ameliorates renal dysfunction and organ damage associated with ANG II-induced hypertension in female mice. ANG II (700 ng.kg(-1).min(-1)) infused by miniosmotic pumps for 2 wk in female Cyp1b1(+/+) mice did not alter water consumption, urine output, Na+ excretion, osmolality, or protein excretion. However, in Cyp1b1(-/-) mice, ANG II infusion significantly increased (P < 0.05) water intake (5.50 +/- 0.42 ml/24 h with vehicle vs. 8.80 +/- 0.60 ml/24 h with ANG II), urine output (1.44 +/- 0.37 ml/24 h with vehicle vs. 4.30 +/- 0.37 ml/24 h with ANG II), and urinary Na+ excretion (0.031 +/- 0.016 mmol/24 h with vehicle vs. 0.099 +/- 0.010 mmol/24 h with ANG II), decreased osmolality (2,630 +/- 79 mosM/kg with vehicle vs. 1,280 +/- 205 mosM/kg with ANG II), and caused proteinuria (2.60 +/- 0.30 mg/24 h with vehicle vs. 6.96 +/- 0.55 mg/24 h with ANG II). Infusion of ANG II caused renal fibrosis, as indicated by an accumulation of renal interstitial alpha-smooth muscle actin, collagen, and transforming growth factor-beta in Cyp1b1(-/-) but not Cyp1b1(+/+) mice. ANG II also increased renal production of ROS and urinary excretion of thiobarburic acid-reactive substances and reduced the activity of antioxidants and urinary excretion of nitrite/nitrate and the 17 beta-estradiol metabolite 2-methoxyestradiol in Cyp1b1(-/-) but not Cyp1b1(+/+) mice. These data suggest that Cyp1b1 plays a critical role in female mice in protecting against renal dysfunction and end-organ damage associated with ANG II-induced hypertension, in preventing oxidative stress, and in increasing activity of antioxidant systems, most likely via generation of 2-methoxyestradiol from 17 beta-estradiol. C1 [Jennings, Brett L.; Moore, Joseph A.; Pingili, Ajeeth K.; Estes, Anne M.; Fang, Xiao R.; Malik, Kafait U.] Univ Tennessee, Dept Pharmacol, Coll Med, Hlth Sci Ctr, Memphis, TN 38163 USA. [Kanu, Alie] Univ Tennessee, Dept Physiol, Coll Med, Hlth Sci Ctr, Memphis, TN 38163 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Malik, KU (reprint author), Univ Tennessee, Dept Pharmacol, Coll Med, Hlth Sci Ctr, 874 Union Ave, Memphis, TN 38163 USA. EM kmalik@uthsc.edu FU National Heart, Lung, and Blood Institute Grants [R01-HL-19134-38-39, K01-HL-96410-04]; American Society of Pharmacology and Experimental Therapeutics FX This work was supported by National Heart, Lung, and Blood Institute Grants R01-HL-19134-38-39 (to K. U. Malik) and K01-HL-96410-04 (to A. Kanu). J. A. Moore was supported by a summer student fellowship from the American Society of Pharmacology and Experimental Therapeutics. NR 65 TC 2 Z9 2 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY 1 PY 2015 VL 308 IS 9 BP F981 EP F992 DI 10.1152/ajprenal.00597.2014 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA CH3VD UT WOS:000353957700004 PM 25694484 ER PT J AU Davis, AS Taubenberger, JK Bray, M AF Davis, A. Sally Taubenberger, Jeffery K. Bray, Mike TI The use of nonhuman primates in research on seasonal, pandemic and avian influenza, 1893-2014 SO ANTIVIRAL RESEARCH LA English DT Review DE Influenza A virus; Nonhuman primate; Experimental infection; Coinfection; Pneumonia; Pathogenesis ID A H5N1 VIRUS; EXPERIMENTAL RESPIRATORY-INFECTIONS; DEPENDENT CELLULAR CYTOTOXICITY; POLYRIBOCYTIDYLIC ACID COMPLEX; MACAQUES MACACA-FASCICULARIS; GORILLA-GORILLA-GORILLA; SQUIRREL-MONKEYS; CYNOMOLGUS-MACAQUES; H1N1 INFLUENZA; RHESUS-MONKEYS AB Attempts to reproduce the features of human influenza in laboratory animals date from the early 1890s, when Richard Pfeiffer inoculated apes with bacteria recovered from influenza patients and produced a mild respiratory illness. Numerous studies employing nonhuman primates (NHPs) were performed during the 1918 pandemic and the following decade. Most used bacterial preparations to infect animals, but some sought a filterable agent for the disease. Since the viral etiology of influenza was established in the early 1930s, studies in NHPs have been supplemented by a much larger number of experiments in mice, ferrets and human volunteers. However, the emergence of a novel swine-origin H1N1 influenza virus in 1976 and the highly pathogenic H5N1 avian influenza virus in 1997 stimulated an increase in NHP research, because these agents are difficult to study in naturally infected patients and cannot be administered to human volunteers. In this paper, we review the published literature on the use of NHPs in influenza research from 1893 through the end of 2014. The first section summarizes observational studies of naturally occurring influenza-like syndromes in wild and captive primates, including serologic investigations. The second provides a chronological account of experimental infections of NHPs, beginning with Pfeiffer's study and covering all published research on seasonal and pandemic influenza viruses, including vaccine and antiviral drug testing. The third section reviews experimental infections of NHPs with avian influenza viruses that have caused disease in humans since 1997. The paper concludes with suggestions for further studies to more clearly define and optimize the role of NHPs as experimental animals for influenza research. Published by Elsevier B.V. C1 [Davis, A. Sally; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Davis, A. Sally] Kansas State Univ, Coll Vet Med, Dept Diagnost Med & Pathobiol, Manhattan, KS 66506 USA. [Bray, Mike] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 33 North Dr,Room 3E19A-2 MSC 3203, Bethesda, MD 20892 USA. EM taubenbergerj@niaid.nih.gov OI Davis, Anne/0000-0001-5711-3936 FU Intramural Research Program of NIAID FX This work was supported by the Intramural Research Program of NIAID. NR 249 TC 8 Z9 8 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 EI 1872-9096 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 2015 VL 117 BP 75 EP 98 DI 10.1016/j.antiviral.2015.02.011 PG 24 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA CH0TH UT WOS:000353734800010 PM 25746173 ER PT J AU Imrich, R Alevizos, I Bebris, L Goldstein, DS Holmes, CS Illei, GG Nikolov, NP AF Imrich, Richard Alevizos, Ilias Bebris, Lolita Goldstein, David S. Holmes, Courtney S. Illei, Gabor G. Nikolov, Nikolay P. TI Predominant Glandular Cholinergic Dysautonomia in Patients With Primary Sjogren's Syndrome SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID DOUBLE-BLIND; FAILURE; NEUROPATHY; SYMPTOMS; DISEASE; TRIAL AB Objective. The autonomic nervous system (ANS) modulates exocrine gland function. Available data show poor correlation between the degree of function and destruction of the exocrine glands in primary Sjogren's syndrome (SS), suggesting that other mechanisms, such as autonomic dysfunction, may be important in these patients. The aim of this study was to perform a comprehensive analysis of sympathoneural and sympathetic cholinergic function in well-characterized patients with primary SS. Methods. Twenty-one patients with primary SS (mean +/- SEM age 44.2 +/- 2.8 years) and 13 healthy control subjects (mean +/- SEM age 50.8 +/- 1.9 years) were assessed during orthostasis and intravenous injection of edrophonium (10 mg). The postganglionic sympathetic cholinergic system was evaluated by assessing sweat production by means of the Quantitative Sudomotor Axon Reflex Test (QSART). Tests of gastric emptying were used to assess the gastrointestinal ANS in primary SS patients. Results. The velocity index and the acceleration index were significantly higher (P < 0.05) in patients with primary SS as compared to controls, both before and during the orthostatic and edrophonium tests. Findings of other hemodynamic and neurochemical parameters did not differ between primary SS patients and controls during the orthostasis and edrophonium test; however, the edrophonium-induced saliva increment was lower in primary SS patients (P = 0.002). Abnormally low sweat production was found in 4 primary SS patients but in none of the controls, as determined by the QSART. Gastric emptying was delayed in 53% of primary SS patients. Conclusion. We observed subtle differences in several ANS domains, including the gastrointestinal and sympathocholinergic systems, suggesting the presence of a complex ANS dysfunction in primary SS. The impact was greatest on the exocrine glands, with subtle differences in the cardiac parasympathetic function that were independent of glandular inflammation and atrophy, suggesting an alternative mechanism of disease pathogenesis in primary SS. C1 [Imrich, Richard] Slovak Acad Sci, Inst Expt Endocrinol, Bratislava 83101, Slovakia. [Alevizos, Ilias; Bebris, Lolita; Illei, Gabor G.; Nikolov, Nikolay P.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Goldstein, David S.; Holmes, Courtney S.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Imrich, R (reprint author), Slovak Acad Sci, Inst Expt Endocrinol, Ctr Mol Med, Vlarska 3-7, Bratislava 83101, Slovakia. EM richard.imrich@savba.sk FU Intramural Research Program of the National Institute of Dental and Craniofacial Research; National Institute of Neurological Disorders and Stroke, NIH FX Supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research and the National Institute of Neurological Disorders and Stroke, NIH. NR 28 TC 1 Z9 1 U1 0 U2 4 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 MAY PY 2015 VL 67 IS 5 BP 1345 EP 1352 DI 10.1002/art.39044 PG 8 WC Rheumatology SC Rheumatology GA CH1IV UT WOS:000353775900025 PM 25622919 ER PT J AU Paczesny, S Hakim, FT Pidala, J Cooke, KR Lathrop, J Griffith, LM Hansen, J Jagasia, M Miklos, D Pavletic, S Parkman, R Russek-Cohen, E Flowers, MED Lee, S Martin, P Vogelsang, G Walton, M Schultz, KR AF Paczesny, Sophie Hakim, Frances T. Pidala, Joseph Cooke, Kenneth R. Lathrop, Julia Griffith, Linda M. Hansen, John Jagasia, Madan Miklos, David Pavletic, Steven Parkman, Robertson Russek-Cohen, Estelle Flowers, Mary E. D. Lee, Stephanie Martin, Paul Vogelsang, Georgia Walton, Marc Schultz, Kirk R. TI National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2014 Biomarker Working Group Report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic graft-versus-host disease; Biomarkers; National Institutes of Health; Consensus ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; REGULATORY T-CELLS; PARAFFIN-EMBEDDED TISSUE; CHILDRENS ONCOLOGY GROUP; SERUM CYTOKINE LEVELS; PREDICT CHRONIC GVHD; PERIPHERAL-BLOOD; GENE POLYMORPHISMS; INCIDENTAL FINDINGS AB Biology-based markers to confirm or aid in the diagnosis or prognosis of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation or monitor its progression are critically needed to facilitate evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biological or pathogenic process, or of a pharmacologic response to a therapeutic intervention. Applications of biomarkers in chronic GVHD clinical trials or patient management include the following: (1) diagnosis and assessment of chronic GVHD disease activity, including distinguishing irreversible damage from continued disease activity; (2) prognostic risk to develop chronic GVHD; and (3) prediction of response to therapy. Sample collection for chronic GVHD biomarkers studies should be well documented following established quality control guidelines for sample acquisition, processing, preservation, and testing, at,intervals that are both calendar and event driven. The consistent therapeutic treatment of subjects and standardized documentation needed to support biomarker studies are most likely to be provided in prospective clinical trials. To date, no chronic GVHD biomarkers have been qualified for use in clinical applications. Since our previous chronic GVHD Biomarkers Working Group report in 2005, an increasing number of chronic GVHD candidate biomarkers are available for further investigation. This paper provides a 4-part framework for biomarker investigations: identification, verification, qualification, and application with terminology based on Food and Drug Administration and European Medicines Agency guidelines. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Paczesny, Sophie] Indiana Univ Med, Dept Pediat & Immunol, Indianapolis, IN USA. [Hakim, Frances T.; Pavletic, Steven] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Pidala, Joseph] H Lee Moffitt Canc Ctr & Res Inst, Blood & Marrow Transplantat, Tampa, FL USA. [Cooke, Kenneth R.; Vogelsang, Georgia] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA. [Lathrop, Julia] Ctr Devices & Radiol Hlth Food & Drug Adm, Off Vitro Diagnost & Radiol Hlth, Silver Spring, MD USA. [Griffith, Linda M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Hansen, John; Flowers, Mary E. D.; Lee, Stephanie; Martin, Paul] Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98195 USA. [Hansen, John; Flowers, Mary E. D.; Lee, Stephanie; Martin, Paul] Univ Washington, Sch Med, Div Med Oncol, Seattle, WA 98195 USA. [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA. [Miklos, David] Stanford Univ, Stanford Bone Marrow Transplant Cellular Therapy, Stanford, CA 94305 USA. [Parkman, Robertson] Univ So Calif, Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA USA. [Russek-Cohen, Estelle] Ctr Biol Food & Drug Adm, Div Biostat, Silver Spring, MD USA. [Walton, Marc] Ctr Drug Evaluat & Res Food & Drug Adm, Off Translat Sci, Silver Spring, MD USA. [Schultz, Kirk R.] BC Childrens Hosp, Michael Cuccione Childhood Canc Res Program, Vancouver, BC, Canada. [Schultz, Kirk R.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Paczesny, S (reprint author), 1044 W Walnut St,Room R4-425, Indianapolis, IN 46202 USA. EM sophpacz@iu.edu FU National Institutes of Health's (NIH's) National Cancer Institute, Center for Cancer Research, Intramural Research Program and Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program; Office of Rare Disease Research, National Center for Advancing Translational Sciences; Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources; Office of Rare Diseases Research/National Center for Advancing Translational Sciences and National Cancer Institute FX This project Was supported by the National Institutes of Health's (NIH's) National Cancer Institute, Center for Cancer Research, Intramural Research Program and Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program; Office of Rare Disease Research, National Center for Advancing Translational Sciences; Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources. The authors acknowledge the following individuals and organizations that, by their participation, made this project possible: American Society for Blood and Marrow Transplantation, Center for International Bone and Marrow Transplant Research, US Chronic GVHD Consortium (supported by Office of Rare Diseases Research/National Center for Advancing Translational Sciences and National Cancer Institute), German-Austrian-Swiss chronic GVHD Consortium, National Marrow Donor Program, the Health Resources and Services Administration, Division of Transplantation, US Department of Human Health and Services, Canadian Blood and Marrow Transplant Group, European Group for Blood and Marrow Transplantation, Pediatric Blood and Marrow Transplant Consortium, and the representatives of the Brazilian Chronic GVHD consortium (Drs. Maria Claudia Moreira, Marcia de Matos Silva and Vaneuza Funke) and Deutsche Jose Carreras Leukamie-Stiftung. The authors thank Dr. Joseph Antin (Dana Farber Cancer Center, Boston, MA), Dr. Hildegard Greinix (Medical University of Vienna, Vienna, Austria), and Dr. Gerard Socie (University Paris VII & AP-HP, Hospital Saint Louis, Paris, France) for their critical review of the manuscript. The organizers are in debt to patients and patient and research advocacy groups, who made this process much more meaningful by their engagement. Acknowledgement goes to the Meredith Cowden GVHD foundation for facilitating the initial planning meeting in Cleveland in November of 2013 in conjunction with the National GVHD Symposium. The project group also recognizes the contributions of numerous colleagues in the field of blood and marrow transplantation in the United States and internationally, medical specialists and consultants, the pharmaceutical industry, and the NIH and US Food and Drug Administration professional staff for their intellectual input, dedication, and enthusiasm on the road to completion of these documents. For their expert contributions to this 2014 NIH Biomarkers Consensus Working Group document, special acknowledgements to Ms. Licia Masuch, Ms. Kristie Bradley, and Ms. Linda Henson for assistance in the manuscript preparation. The opinions expressed are those of the authors and do not represent the position of the National Cancer Institute; the National Heart, Lung and Blood Institute; the National Institute of Allergy and Infectious Diseases; the National Institutes of Health; the Food and Drug Administration; or the United States government. NR 97 TC 15 Z9 15 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2015 VL 21 IS 5 BP 780 EP 792 DI 10.1016/j.bbna.2015.01.003 PG 13 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CH2LM UT WOS:000353856700002 PM 25644957 ER PT J AU Chokshi, P Anandi, P Jain, N Dunavin, N Le, RQ Ito, S Barrett, J Battiwalla, M AF Chokshi, Puja Anandi, Prathima Jain, Natasha Dunavin, Neil Le, Robert Q. Ito, Sawa Barrett, John Battiwalla, Minoo TI Minor ABO Incompatibility Does Not Impact Nonrelapse Mortality in T Cell-Depleted Human Leukocyte Antigen-Matched Sibling Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Letter ID BONE-MARROW-TRANSPLANTATION; TISSUE DISTRIBUTION C1 [Chokshi, Puja; Anandi, Prathima; Jain, Natasha; Dunavin, Neil; Le, Robert Q.; Ito, Sawa; Barrett, John; Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Battiwalla, M (reprint author), NHLBI, Hematol Branch, NIH, 10-CRC,Rm 3-5330,10 Ctr Dr, Bethesda, MD 20892 USA. EM minoo.battiwalla@nih.gov NR 7 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2015 VL 21 IS 5 BP 954 EP 955 DI 10.1016/j.bbmt.2015.02.020 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CH2LM UT WOS:000353856700023 PM 25711513 ER PT J AU Wang, QS Qian, L Chen, SH Chu, CH Wilson, B Oyarzabal, E Ali, S Robinson, B Rao, D Hong, JS AF Wang, Qingshan Qian, Li Chen, Shih-Heng Chu, Chun-Hsien Wilson, Belinda Oyarzabal, Esteban Ali, Syed Robinson, Bonnie Rao, Deepa Hong, Jau-Shyong TI Post-treatment with an ultra-low dose of NADPH oxidase inhibitor diphenyleneiodonium attenuates disease progression in multiple Parkinson's disease models SO BRAIN LA English DT Article DE Parkinson's disease; microglia; NADPH oxidase; neuroinflammation; superoxide ID DOPAMINERGIC NEURODEGENERATION; MPTP MODEL; CHRONIC NEUROINFLAMMATION; MICROGLIAL ACTIVATION; REACTIVE MICROGLIOSIS; OXIDATIVE STRESS; ALPHA-SYNUCLEIN; ANIMAL-MODEL; NOX ENZYMES; NEUROPROTECTION AB Nicotinamide adenine dinucleotide phosphate oxidase, a key superoxide-producing enzyme, plays a critical role in microglia-mediated chronic neuroinflammation and subsequent progressive dopaminergic neurodegeneration in Parkinson's disease. Although nicotinamide adenine dinucleotide phosphate oxidase-targeting anti-inflammatory therapy for Parkinson's disease has been proposed, its application in translational research remains limited. The aim of this study was to obtain preclinical evidence supporting this therapeutic strategy by testing the efficacy of an ultra-low dose of the nicotinamide adenine dinucleotide phosphate oxidase inhibitor diphenyleneiodonium in both endotoxin (lipopolysaccharide)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice using post-treatment regimens. Our data revealed that post-treatment with diphenyleneiodonium significantly attenuated progressive dopaminergic degeneration and improved rotarod activity. Remarkably, post-treatment with diphenyleneiodonium 10 months after lipopolysaccharide injection when mice had 30% loss of nigral dopaminergic neurons, showed high efficacy in protecting the remaining neuronal population and restoring motor function. Diphenyleneiodonium-elicited neuroprotection was associated with the inhibition of microglial activation, a reduction in the expression of proinflammatory factors and an attenuation of alpha-synuclein aggregation. A pathophysiological evaluation of diphenyleneiodonium-treated mice, including assessment of body weight, organs health, and neuronal counts, revealed no overt signs of toxicity. In summary, infusion of ultra-low dose diphenyleneiodonium potently reduced microglia-mediated chronic neuroinflammation by selectively inhibiting nicotinamide adenine dinucleotide phosphate oxidase and halted the progression of neurodegeneration in mouse models of Parkinson's disease. The robust neuroprotective effects and lack of apparent toxic side effects suggest that diphenyleneiodonium at ultra-low dose may be a promising candidate for future clinical trials in Parkinson's disease patients. C1 [Wang, Qingshan; Qian, Li; Chen, Shih-Heng; Chu, Chun-Hsien; Wilson, Belinda; Oyarzabal, Esteban; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. [Ali, Syed; Robinson, Bonnie] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Rao, Deepa] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Wang, QS (reprint author), NIEHS, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM wangq4@niehs.nih.gov; hong3@niehs.nih.gov FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences NR 49 TC 5 Z9 6 U1 0 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD MAY 1 PY 2015 VL 138 BP 1247 EP 1262 DI 10.1093/brain/awv034 PN 5 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CH2DB UT WOS:000353834100022 PM 25716193 ER PT J AU Maity, TK Venugopalan, A Linnoila, I Cultraro, CM Giannakou, A Nemati, R Zhang, X Webster, JD Ritt, D Ghosal, S Hoschuetzky, H Simpson, RM Biswas, R Politi, K Morrison, DK Varmus, HE Guha, U AF Maity, Tapan K. Venugopalan, Abhilash Linnoila, Ilona Cultraro, Constance M. Giannakou, Andreas Nemati, Roxanne Zhang, Xu Webster, Joshua D. Ritt, Daniel Ghosal, Sarani Hoschuetzky, Heinz Simpson, R. Mark Biswas, Romi Politi, Katerina Morrison, Deborah K. Varmus, Harold E. Guha, Udayan TI Loss of MIG6 Accelerates Initiation and Progression of Mutant Epidermal Growth Factor Receptor-Driven Lung Adenocarcinoma SO CANCER DISCOVERY LA English DT Article ID KINASE DOMAIN; EGF RECEPTOR; ACQUIRED-RESISTANCE; DOWN-REGULATION; GENE-MUTATIONS; MESENCHYMAL TRANSITION; ACTIVATING MUTATIONS; NEVER-SMOKERS; CANCER; GEFITINIB AB Somatic mutations in the EGFR kinase domain drive lung adenocarcinoma. We have previously identified MIG6, an inhibitor of ERBB signaling and a potential tumor suppressor, as a target for phosphorylation by mutant EGFRs. Here, we demonstrate that MIG6 is a tumor suppressor for the initiation and progression of mutant EGFR-driven lung adenocarcinoma in mouse models. Mutant EGFR-induced lung tumor formation was accelerated in Mig6-deficient mice, even with Mig6 haploinsufficiency. We demonstrate that constitutive phosphorylation of MIG6 at Y394/Y395 in EGFR-mutant human lung adenocarcinoma cell lines is associated with an increased interaction of MIG6 with mutant EGFR, which may stabilize EGFR protein. MIG6 also fails to promote mutant EGFR degradation. We propose a model whereby increased tyrosine phosphorylation of MIG6 decreases its capacity to inhibit mutant EGFR. Nonetheless, the residual inhibition is sufficient for MIG6 to delay mutant EGFR-driven tumor initiation and progression in mouse models. SIGNIFICANCE: This study demonstrates that MIG6 is a potent tumor suppressor for mutant EGFR-driven lung tumor initiation and progression in mice and provides a possible mechanism by which mutant EGFR can partially circumvent this tumor suppressor in human lung adenocarcinoma. (C) 2015 AACR. C1 [Maity, Tapan K.; Venugopalan, Abhilash; Cultraro, Constance M.; Nemati, Roxanne; Zhang, Xu; Ghosal, Sarani; Biswas, Romi; Guha, Udayan] NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Linnoila, Ilona] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Giannakou, Andreas; Politi, Katerina; Varmus, Harold E.; Guha, Udayan] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA. [Webster, Joshua D.; Simpson, R. Mark] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Ritt, Daniel; Morrison, Deborah K.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21701 USA. [Hoschuetzky, Heinz] NanoTools, Teningen, Germany. RP Guha, U (reprint author), NCI, 10 Ctr Dr, Bethesda, MD 20892 USA. EM udayan.guha@nih.gov FU National Cancer Institute Center for Cancer Research (NCI-CCR) Intramural Research Program [ZIA BC 011259]; K99 Career Transition Award [K99CA140792]; [PO1 CA129243] FX This work was supported by the National Cancer Institute Center for Cancer Research (NCI-CCR) Intramural Research Program ZIA BC 011259 (to U. Guha), a K99 Career Transition Award (K99CA140792; to U. Guha), and PO1 CA129243 (to H.E. Varmus). NR 60 TC 7 Z9 7 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD MAY PY 2015 VL 5 IS 5 BP 534 EP 549 DI 10.1158/2159-8290.CD-14-0750 PG 16 WC Oncology SC Oncology GA CH0HI UT WOS:000353700000025 PM 25735773 ER PT J AU Wibom, C Spath, F Dahlin, AM Langseth, H Hovig, E Rajaraman, P Johannesen, TB Andersson, U Melin, B AF Wibom, Carl Spath, Florentin Dahlin, Anna M. langseth, HilDe Hovig, Eivind Rajaraman, Preetha Johannesen, Tom Borge Andersson, Ulrika Melin, Beatrice TI Investigation of Established Genetic Risk Variants for Glioma in Prediagnostic Samples from a Population-Based Nested Case-Control Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; NERVOUS-SYSTEM TUMORS; JANUS-SERUM-BANK; TELOMERE LENGTH; CAPILLARY-ELECTROPHORESIS; CANCER SUSCEPTIBILITY; 1ST-DEGREE RELATIVES; IONIZING-RADIATION; BRAIN; GLIOBLASTOMA AB Background: Although glioma etiology is poorly understood in general, growing evidence indicates a genetic component. Four large genome-wide association studies (GWAS) have linked common genetic variants with an increased glioma risk. However, to date, these studies are based largely on a case-control design, where cases have been recruited at the time of or after diagnosis. They may therefore suffer from a degree of survival bias, introduced when rapidly fatal cases are not included. Methods: To confirm glioma risk variants in a prospective setting, we have analyzed 11 previously identified risk variants in a set of prediagnostic serum samples with 598 cases and 595 matched controls. Serum samples were acquired from The Janus Serum Bank, a Norwegian population-based biobank reserved for cancer research. Results: We confirmed the association with glioma risk for variants within five genomic regions: 8q24.21 (CCDC26), 9p21.3 (CDKN2B-AS1), 11q23.3 (PHLDB1), 17p13.1 (TP53), and 20q13.33 (RTEL1). However, previously identified risk variants within the 7p11.2 (EGFR) region were not confirmed by this study. Conclusions: Our results indicate that the risk variants that were confirmed by this study are truly associated with glioma risk and may, consequently, affect gliomagenesis. Though the lack of positive confirmation of EGFR risk variants may be attributable to relatively limited statistical power, it nevertheless raises the question whether they truly are risk variants or markers for glioma prognosis. Impact: Our findings indicate the need for further studies to clarify the role of glioma risk loci with respect to prolonged survival versus etiology. (C) 2015 AACR. C1 [Wibom, Carl; Spath, Florentin; Dahlin, Anna M.; Andersson, Ulrika; Melin, Beatrice] Umea Univ, Dept Radiat Sci, Oncol, S-90187 Umea, Sweden. [Wibom, Carl; Dahlin, Anna M.] Umea Univ, Computat Life Sci Cluster CLiC, S-90187 Umea, Sweden. [langseth, HilDe] Canc Registry Norway, Inst Populat Based Canc Res, Dept Res, Oslo, Norway. [Hovig, Eivind] Norwegian Radium Hosp, Inst Canc Res, Dept Tumor Biol, Oslo, Norway. [Hovig, Eivind] Univ Oslo, Dept Informat, N-0316 Oslo, Norway. [Rajaraman, Preetha] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Johannesen, Tom Borge] Canc Registry Norway, Inst Populat Based Canc Res, Oslo, Norway. RP Wibom, C (reprint author), Umea Univ, Computat Life Sci Cluster CLiC, KBC Bldg,4th Floor, S-90187 Umea, Sweden. EM carl.wibom@onkologi.umu.se RI Hovig, Eivind/H-2474-2011 OI Hovig, Eivind/0000-0002-9103-1077 FU Acta Oncologica foundation through the Royal Swedish Academy of Science; Swedish Research Council; Swedish Cancer Foundation; Northern Sweden Cancer Foundation; Umea University Young investigator reward; Umea Hospital Cutting Edge Grant FX B. Melin was supported by grants from Acta Oncologica foundation through the Royal Swedish Academy of Science (salary), The Swedish Research Council, Swedish Cancer Foundation, Northern Sweden Cancer Foundation, Umea University Young investigator reward, and Umea Hospital Cutting Edge Grant. NR 32 TC 3 Z9 3 U1 0 U2 2 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 MAY PY 2015 VL 24 IS 5 BP 810 EP 816 DI 10.1158/1055-9965.EPI-14-1106 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CH0IK UT WOS:000353702800006 PM 25713050 ER PT J AU Kuhs, KAL Hildesheim, A Trabert, B Kemp, TJ Purdue, MP Wentzensen, N Katki, HA Pinto, LA Loftfield, E Safaeian, M Chaturvedi, AK Shiels, MS AF Kuhs, Krystle A. Lang Hildesheim, Allan Trabert, Britton Kemp, Troy J. Purdue, Mark P. Wentzensen, Nicolas Katki, Hormuzd A. Pinto, Ligia A. Loftfield, Erikka Safaeian, Mahboobeh Chaturvedi, Anil K. Shiels, Meredith S. TI Association between Regular Aspirin Use and Circulating Markers of Inflammation: A Study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NON-HODGKIN-LYMPHOMA; C-REACTIVE PROTEIN; LOW-DOSE ASPIRIN; TUMOR ANGIOGENESIS; RANDOMIZED-TRIALS; SERUM-LEVELS; RISK; CYTOKINES; CLOPIDOGREL; METASTASIS AB Background: Regular aspirin use may decrease cancer risk by reducing chronic inflammation. However, associations between aspirin use and circulating markers of inflammation have not been well studied. Methods: Serum levels of 78 inflammatory markers were measured in 1,819 55-to 74-year-old men and women in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Data were combined from three completed case-control studies and reweighted to the PLCO screening arm. Self-reported aspirin and ibuprofen use (number of tablets taken per day/week/month) over the previous 12 months was collected at baseline. Associations between (i) nonregular (< 4 tablets/month), (ii) low (1-4 tablets/week), (iii) moderate (1 tablet/day), or (iv) high (2+tablets/day) regular aspirin or ibuprofen use and marker levels were assessed with weighted logistic regression. Results: Aspirin use was nominally associated with (P-trend across categories <= 0.05) decreased levels of chemokine C-C motif ligand 15 [CCL15; OR, 0.5; 95% confidence intervals (CI), 0.3-0.8; moderate versus nonregular use]; soluble vascular endothelial growth factor receptor 2 (sVEGFR2; OR, 0.7; 95% CI, 0.4-1.0); soluble tumor necrosis factor receptor 1 (sTNFR1; OR, 0.6; 95% CI, 0.4-0.9) and increased levels of CCL13 (OR, 1.3; 95% CI, 0.8-2.1); CCL17 (OR, 1.1; 95% CI, 0.7-1.9) and interleukin 4 (IL4; OR, 1.6; 95% CI, 0.9-2.8). Trends were not statistically significant following correction for multiple comparisons. Likewise, no statistically significant associations were observed between ibuprofen use and marker levels. Conclusions: No significant associations were observed between regular aspirin use and the inflammatory markers assessed. Impact: Additional studies are needed to better understand the relationship between aspirin use, chronic inflammation, and cancer risk. (C) 2015 AACR. C1 [Kuhs, Krystle A. Lang; Hildesheim, Allan; Trabert, Britton; Purdue, Mark P.; Wentzensen, Nicolas; Katki, Hormuzd A.; Loftfield, Erikka; Safaeian, Mahboobeh; Chaturvedi, Anil K.; Shiels, Meredith S.] NCI, NIH, Bethesda, MD 20892 USA. [Kemp, Troy J.; Pinto, Ligia A.] Leidos Biomed Res Inc, HPV Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA. [Purdue, Mark P.] Ontario Inst Canc Res, Toronto, ON, Canada. RP Kuhs, KAL (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6-E210, Bethesda, MD 20892 USA. EM Krystle.Kuhs@nih.gov RI Hildesheim, Allan/B-9760-2015; Purdue, Mark/C-9228-2016; Trabert, Britton/F-8051-2015; Chaturvedi, Anil/J-2024-2015 OI Hildesheim, Allan/0000-0003-0257-2363; Purdue, Mark/0000-0003-1177-3108; Chaturvedi, Anil/0000-0003-2696-8899 FU Intramural Research Program of the National Cancer Institute FX This work was supported by the Intramural Research Program of the National Cancer Institute (all authors received). NR 40 TC 2 Z9 3 U1 1 U2 8 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 MAY PY 2015 VL 24 IS 5 BP 825 EP 832 DI 10.1158/1055-9965.EPI-14-1363 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CH0IK UT WOS:000353702800008 PM 25713025 ER PT J AU Ochs-Balcom, HM Phillips, LS Nichols, HB Martinez, E Thompson, B Ojeifo, J Rebbeck, TR AF Ochs-Balcom, Heather M. Phillips, Lynette S. Nichols, Hazel B. Martinez, Elena Thompson, Beti Ojeifo, John Rebbeck, Timothy R. TI Building a Funded Research Program in Cancer Health Disparities: Considerations for Young Investigators SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material AB A workshop entitled "Building a funded research program in cancer health disparities" was held at the 38th Annual American Society of Preventive Oncology (ASPO) Meeting. Organized by the Junior Members Interest Group, the session addressed topics relevant to career development for cancer disparities investigators. Such considerations include the development of research programs on a backdrop of existing multi- and transdisciplinary teams, recognizing opportunities for advancing their research, given the growth of consortia-related research, and development of effective community-based partnerships. Key strategies for developing a sustainable career in cancer health disparities in the current environment include the need to effectively engage with communities, appreciate the value of team science and develop cross-discipline collaborations, and navigate the use and utility of consortia for disparities research. Academic considerations related to earning tenure and promotion that may be faced by the junior investigator in cancer health disparities were also discussed. This report may serve to both educate and provide lessons for early-stage investigators who wish to tackle complex scientific questions while developing their careers in cancer health disparities. (C) 2015 AACR. C1 [Ochs-Balcom, Heather M.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Epidemiol & Environm Hlth, Buffalo, NY 14214 USA. [Phillips, Lynette S.] Kent State Univ, Coll Publ Hlth, Kent, OH 44242 USA. [Nichols, Hazel B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Martinez, Elena] Univ Calif San Diego, Family & Prevent Med, La Jolla, CA 92093 USA. [Thompson, Beti] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Thompson, Beti] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Ojeifo, John] Ctr Reduce Canc Hlth Dispar, Divers Training Branch, NIH, Bethesda, MD USA. [Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Ochs-Balcom, HM (reprint author), SUNY Buffalo, 270 Farber Hall, Buffalo, NY 14214 USA. EM hmochs2@buffalo.edu FU NIH/NCI [K07CA136969]; Susan G. Komen for the Cure [KG090937] FX The authors thank the members of the ASPO Junior Members Interest Group, especially Drs. Marlyn Allicock, Tomi Akinyemiju, Adana Llanos, and Kathryn Roysewho helped organize the session, as well as Heidi Sahel for session logistics. Dr. Ochs-Balcom received grant support from the NIH/NCI (K07CA136969) and Susan G. Komen for the Cure (KG090937). NR 5 TC 1 Z9 1 U1 2 U2 4 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 MAY PY 2015 VL 24 IS 5 BP 882 EP 885 DI 10.1158/1055-9965.EPI-15-0136 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CH0IK UT WOS:000353702800018 PM 25934837 ER PT J AU Medina-Echeverz, J Ma, C Duffy, AG Eggert, T Hawk, N Kleiner, DE Korangy, F Greten, TF AF Medina-Echeverz, Jose Ma, Chi Duffy, Austin G. Eggert, Tobias Hawk, Nga Kleiner, David E. Korangy, Firouzeh Greten, Tim F. TI Systemic Agonistic Anti-CD40 Treatment of Tumor-Bearing Mice Modulates Hepatic Myeloid-Suppressive Cells and Causes Immune-Mediated Liver Damage SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY THERAPY; A-INDUCED HEPATITIS; HEPATOCELLULAR-CARCINOMA; ANTITUMOR VACCINE; REACTIVE OXYGEN; MURINE MODELS; CD40 ANTIBODY; CANCER; IMMUNOTHERAPY; MICROENVIRONMENT AB Immune-stimulatory mAbs are currently being evaluated as antitumor agents. Although overall toxicity from these agents appears to be moderate, liver toxicities have been reported and are not completely understood. We studied the effect of systemic CD40 antibody treatment on myeloid cells in the spleen and liver. Naive and tumor-bearing mice were treated systemically with agonistic anti-CD40 antibody. Immune cell subsets in the liver and spleen, serum transaminases, and liver histologies were analyzed after antibody administration. Nox2(-/-), Cd40(-/-), and bone marrow chimeric mice were used to study the mechanism by which agonistic anti-CD40 mediates its effects in vivo. Suppressor function of murine and human tumor-induced myeloid-derived suppressor cells (MDSC) was studied upon CD40 ligation. Agonistic CD40 antibody caused liver damage within 24 hours after injection in two unrelated tumor models and mice strains. Using bone marrow chimeras, we demonstrate that CD40 antibody-induced hepatitis in tumor-bearing mice was dependent on the presence of CD40-expressing hematopoietic cells. Agonistic CD40 ligation-dependent liver damage was induced by the generation of reactive oxygen species. Furthermore, agonistic CD40 antibody resulted in increased CD80-positive and CD40-positive liver CD11b(+)Gr-1(+) immature myeloid cells. CD40 ligation on tumor-induced murine and human CD14(+)HLA-DRlow peripheral blood mononuclear cells from patients with cancer reduced their immune suppressor function. Collectively, agonistic CD40 antibody treatment activated tumor-induced myeloid cells, caused myeloid-dependent hepatotoxicity, and ameliorated the suppressor function of murine and human MDSC. Collectively, our data suggest that CD40 may mature immunosuppressive myeloid cells and thereby cause liver damage in mice with an accumulation of tumor-induced hepatic MDSC. (c) 2015 AACR. C1 [Medina-Echeverz, Jose; Ma, Chi; Duffy, Austin G.; Eggert, Tobias; Korangy, Firouzeh; Greten, Tim F.] NCI, Gastrointestinal Malignancy Sect, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Hawk, Nga] NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Greten, TF (reprint author), NCI, NIH, 10 Ctr Dr,Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM tim.greten@nih.gov FU Intramural Research Program of the NCI, NIH FX This work was supported by the Intramural Research Program of the NCI, NIH. NR 51 TC 5 Z9 5 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD MAY PY 2015 VL 3 IS 5 BP 557 EP 566 DI 10.1158/2326-6066.CIR-14-0182 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA CH0HX UT WOS:000353701500016 PM 25637366 ER PT J AU Greene, MH Mai, PL AF Greene, Mark H. Mai, Phuong L. TI The Fallopian Tube: From Back Stage to Center Stage SO CANCER PREVENTION RESEARCH LA English DT Editorial Material ID REDUCING SALPINGO-OOPHORECTOMY; GYNECOLOGIC-ONCOLOGY-GROUP; OVARIAN-CANCER; INTRAEPITHELIAL CARCINOMA; MUTATION CARRIERS; BRCA2 MUTATION; RISK; WOMEN; FAMILIES; FIMBRIA AB The recognition that a significant fraction of what historically has been classified as ovarian cancer is, in fact, a malignancy that arises in the fallopian tube mucosa comprises a paradigm shift in our understanding of these neoplasms. New etiologic and management opportunities have been created by this insight, both for women at increased genetic risk of ovarian cancer by virtue of being BRCA1/2 mutation carriers and, perhaps, for women in the general population as well. Cancer (C) 2015 AACR. C1 [Greene, Mark H.; Mai, Phuong L.] NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD 20850 USA. RP Greene, MH (reprint author), NCI, Clin Genet Branch, NIH, 9609 Med Ctr Dr,Room 6E-454, Rockville, MD 20850 USA. EM greenem@mail.nih.gov FU Intramural NIH HHS [ZIA CP010144-15] NR 24 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD MAY PY 2015 VL 8 IS 5 BP 339 EP 341 DI 10.1158/1940-6207.CAPR-15-0072 PG 3 WC Oncology SC Oncology GA CH0IY UT WOS:000353704300001 PM 25802341 ER PT J AU St Croix, B AF St Croix, Brad TI CD146: the unveiling of a pro-angiogenic netrin receptor SO CELL RESEARCH LA English DT Editorial Material AB Netrin-1, a classic neuronal guidance cue, can promote angiogenesis under certain developmental and pathological conditions, but key receptors on vascular endothelium have remained elusive. A recent study published in Cell Research by Tu et al. reveals that CD146, an endothelial receptor of the immunoglobulin superfamily, binds netrin-1 with high affinity and may play an important role in regulating angiogenesis. C1 NCI, Tumor Angiogenesis Sect, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. RP St Croix, B (reprint author), NCI, Tumor Angiogenesis Sect, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. EM stcroix@ncifcrf.gov NR 12 TC 1 Z9 1 U1 0 U2 5 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD MAY PY 2015 VL 25 IS 5 BP 533 EP 534 DI 10.1038/cr.2015.42 PG 2 WC Cell Biology SC Cell Biology GA CH3GP UT WOS:000353917500003 PM 25849249 ER PT J AU Boyiadzis, M Arora, M Klein, JP Hassebroek, A Hemmer, M Urbano-Ispizua, A Antin, JH Bolwell, BJ Cahn, JYY Cairo, MS Cutler, CS Flowers, ME Gale, RP Herzig, R Isola, LM Jacobsohn, DA Jagasia, MH Klumpp, TR Lee, SJ Petersdorf, EW Santarone, S Spellman, SR Schouten, HC Verdonck, LF Wingard, JR Weisdorf, DJ Horowitz, MM Pavletic, SZ AF Boyiadzis, Michael Arora, Mukta Klein, John P. Hassebroek, Anna Hemmer, Michael Urbano-Ispizua, Alvaro Antin, Joseph H. Bolwell, Brian J. Cahn, Jean-Yves Y. Cairo, Mitchell S. Cutler, Corey S. Flowers, Mary E. Gale, Robert P. Herzig, Roger Isola, Luis M. Jacobsohn, David A. Jagasia, Madan H. Klumpp, Thomas R. Lee, Stephanie J. Petersdorf, Effie W. Santarone, Stella Spellman, Stephen R. Schouten, Harry C. Verdonck, Leo F. Wingard, John R. Weisdorf, Daniel J. Horowitz, Mary M. Pavletic, Steven Z. TI Impact of Chronic Graft-versus-Host Disease on Late Relapse and Survival on 7,489 Patients after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID BONE-MARROW-TRANSPLANTATION; UNRELATED DONOR TRANSPLANTATION; HLA-IDENTICAL SIBLINGS; LEUKOCYTE INFUSIONS; MYELOID-LEUKEMIA; EUROPEAN GROUP; MORTALITY; BLOOD AB Purpose: Malignancy relapse remains a major obstacle for successful allogeneic hematopoietic cell transplantation (HCT). Chronic graft-versus-host disease (cGVHD) is associated with fewer relapses. However, when studying effects of cGVHD on relapse, it is difficult to separate from acute GVHD effects as most cases of cGVHD occur within the first year after transplant at the time when acute GVHD is still active. Experimental Design: This study based on CIBMTR registry data investigated cGVHD and its association with the incidence of late relapse and survival in 7,489 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndromes (MDS), who were leukemia free at 12 months after myeloablative allogeneic HCT. Results: Forty-seven percent of the study population was diagnosed with cGVHD at 12 months after transplant. The protective effect of cGVHD on late relapse was present only in patients with CML [RR, 0.47; 95% confidence interval (CI), 0.37-0.59; P < 0.0001). cGVHD was significantly associated with higher risk of treatment-related mortality (TRM; RR, 2.43; 95% CI, 2.09-2.82; P < 0.0001) and inferior overall survival (RR, 1.56; 95% CI, 1.41-1.73; P < 0.0001) for all diseases. In patients with CML, all organ sites and presentation types of cGVHD were equally associated with lower risk of late relapse. Conclusions: These results indicate that clinically relevant antileukemia effects of cGVHD on late relapses are present only in CML but not in AML, ALL, or MDS. Chronic GVHD in patients who are 1-year survivors after myeloablative allogeneic HCT is primarily associated with higher TRM and inferior survival. (C) 2014 AACR. C1 [Boyiadzis, Michael] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15232 USA. [Arora, Mukta; Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Klein, John P.; Hemmer, Michael; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Hassebroek, Anna; Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Urbano-Ispizua, Alvaro] Hosp Clinic, Inst Hematol & Oncol, Boston, MA USA. [Antin, Joseph H.; Cutler, Corey S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bolwell, Brian J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Cahn, Jean-Yves Y.] CHU Grenoble, Hop Michallon, F-38043 Grenoble, France. [Cairo, Mitchell S.] New York Med Coll, Valhalla, NY 10595 USA. [Flowers, Mary E.; Lee, Stephanie J.; Petersdorf, Effie W.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Gale, Robert P.] Univ London Imperial Coll Sci Technol & Med, London, England. [Herzig, Roger] Univ Louisville, Hosp James Brown Canc Ctr, Louisville, KY 40292 USA. [Isola, Luis M.] Mt Sinai Med Ctr, Miami, FL USA. [Jacobsohn, David A.] Childrens Hosp, Natl Med Ctr, Washington, DC 20010 USA. [Jagasia, Madan H.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Klumpp, Thomas R.] Temple Bone Marrow Transplant Program, Philadelphia, PA USA. [Santarone, Stella] Osped Civile BMT Ctr, Pescara, Italy. [Schouten, Harry C.] Acad Ziekenhuis Maastricht, Maastricht, Netherlands. [Verdonck, Leo F.] Isala Clin, Zwolle, Netherlands. [Wingard, John R.] Shands HealthCare, Gainesville, FL USA. [Wingard, John R.] Univ Florida, Gainesville, FL USA. [Pavletic, Steven Z.] NCI, Bethesda, MD 20892 USA. RP Boyiadzis, M (reprint author), Univ Pittsburgh, Inst Canc, UPMC Canc Pavil,5150 Ctr Ave,Suite 564, Pittsburgh, PA 15232 USA. EM boyiadzism@upmc.edu FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U01HL069294]; Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; Leukemia & Lymphoma Society; Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS, Inc.; Wellpoint, Inc. FX The CIBMTR is supported by Public Health Service grant/cooperative agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a grant/cooperative agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS, Inc.; and Wellpoint, Inc. NR 22 TC 15 Z9 15 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2015 VL 21 IS 9 BP 2020 EP 2028 DI 10.1158/1078-0432.CCR-14-0586 PG 9 WC Oncology SC Oncology GA CH0KK UT WOS:000353708200009 PM 25348512 ER PT J AU Jain, S Jirau-Serrano, X Zullo, KM Scotto, L Palermo, CF Sastra, SA Olive, KP Cremers, S Thomas, T Wei, Y Zhang, Y Bhagat, G Amengual, JE Deng, CC Karan, C Realubit, R Bates, SE O'Connor, OA AF Jain, Salvia Jirau-Serrano, Xavier Zullo, Kelly M. Scotto, Luigi Palermo, Carmine F. Sastra, Stephen A. Olive, Kenneth P. Cremers, Serge Thomas, Tiffany Wei, Ying Zhang, Yuan Bhagat, Govind Amengual, Jennifer E. Deng, Changchun Karan, Charles Realubit, Ronald Bates, Susan E. O'Connor, Owen A. TI Preclinical Pharmacologic Evaluation of Pralatrexate and Romidepsin Confirms Potent Synergy of the Combination in a Murine Model of Human T-cell Lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTEASOME INHIBITOR BORTEZOMIB; SEZARY-SYNDROME; MOUSE MODEL; IN-VITRO; MICE; GROWTH; METHOTREXATE; SUPERIOR; TUMORS AB Purpose: T-cell lymphomas (TCL) are aggressive diseases, which carry a poor prognosis. The emergence of new drugs for TCL has created a need to survey these agents in a rapid and reproducible fashion, to prioritize combinations which should be prioritized for clinical study. Mouse models of TCL that can be used for screening novel agents and their combinations are lacking. Developments in noninvasive imaging modalities, such as surface bioluminescence (SBL) and three-dimensional ultrasound (3D-US), are challenging conventional approaches in xenograft modeling relying on caliper measurements. The recent approval of pralatrexate and romidepsin creates an obvious combination that could produce meaningful activity in TCL, which is yet to be studied in combination. Experimental Design: High-throughput screening and multi-modality imaging approach of SBL and 3D-US in a xenograft NOG mouse model of TCL were used to explore the in vitro and in vivo activity of pralatrexate and romidepsin in combination. Corresponding mass spectrometry-based pharmacokinetic and immunohistochemistry-based pharmacodynamic analyses of xenograft tumors were performed to better understand a mechanistic basis for the drug: drug interaction. Results: In vitro, pralatrexate and romidepsin exhibited concentration-dependent synergism in combination against a panel of TCL cell lines. In aNOG murine model of TCL, the combination of pralatrexate and romidepsin exhibited enhanced efficacy compared with either drug alone across a spectrum of tumors using complementary imaging modalities, such as SBL and 3D-US. Conclusions: Collectively, these data strongly suggest that the combination of pralatrexate and romidepsin merits clinical study in patients with TCLs. (C) 2015 AACR. C1 [Jain, Salvia] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Jirau-Serrano, Xavier; Zullo, Kelly M.; Scotto, Luigi; Amengual, Jennifer E.; Deng, Changchun; O'Connor, Owen A.] Columbia Univ, Med Ctr, Ctr Lymphoid Malignancies, New York, NY 10019 USA. [Jirau-Serrano, Xavier; Zullo, Kelly M.; Scotto, Luigi; Sastra, Stephen A.; Olive, Kenneth P.; Amengual, Jennifer E.; Deng, Changchun; O'Connor, Owen A.] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY 10019 USA. [Palermo, Carmine F.; Sastra, Stephen A.; Olive, Kenneth P.; Cremers, Serge; Thomas, Tiffany; Bhagat, Govind] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10019 USA. [Palermo, Carmine F.; Sastra, Stephen A.; Olive, Kenneth P.; Cremers, Serge] Irving Inst Clin & Translat Res, New York, NY USA. [Palermo, Carmine F.; Sastra, Stephen A.; Olive, Kenneth P.; Cremers, Serge; Amengual, Jennifer E.; Deng, Changchun; O'Connor, Owen A.] Columbia Univ, Med Ctr, Dept Med, New York, NY 10019 USA. [Wei, Ying; Zhang, Yuan] Columbia Univ, Med Ctr, Dept Biostat, New York, NY 10019 USA. [Karan, Charles; Realubit, Ronald] Columbia Univ, Med Ctr, Dept Syst Biol, High Throughput Screening Facil, New York, NY 10019 USA. [Bates, Susan E.] NCI, Dev Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP O'Connor, OA (reprint author), Columbia Univ, Med Ctr, 51 West 51st St, New York, NY 10019 USA. EM oo2130@columbia.edu OI Bhagat, Govind/0000-0001-6250-048X FU Columbia University Lymphoma Research Fund; [S 10 RR025482-01AS10] FX The authors thank the Columbia University Lymphoma Research Fund for support. Imaging studies were performed in collaboration with the Small Animal Imaging Shared Resource within the Herbert Irving Comprehensive Cancer Center (NCI 3 P30 CA13696). The Vexo 2100 ultrasound was purchased from a Small Instrumentation Grant (S 10 RR025482-01AS10). NR 29 TC 6 Z9 6 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2015 VL 21 IS 9 BP 2096 EP 2106 DI 10.1158/1078-0432.CCR-14-2249 PG 11 WC Oncology SC Oncology GA CH0KK UT WOS:000353708200017 PM 25677697 ER PT J AU Weykamp, C John, G Gillery, P English, E Ji, LN Lenters-Westra, E Little, RR Roglic, G Sacks, DB Takei, I AF Weykamp, Cas John, Garry Gillery, Philippe English, Emma Ji, Linong Lenters-Westra, Erna Little, Randie R. Roglic, Gojka Sacks, David B. Takei, Izumi CA IFCC Task Force Implementation HbA TI Investigation of 2 Models to Set and Evaluate Quality Targets for Hb A(1c): Biological Variation and Sigma-Metrics SO CLINICAL CHEMISTRY LA English DT Article ID ANALYTICAL BIAS; IMPRECISION; HBA(1C); NUMBER; LIMITS; GOALS AB BACKGROUND: A major objective of the IFCC Task Force on Implementation of HbA(1c) Standardization is to develop a model to define quality targets for glycated hemoglobin (Hb A(1c)). METHODS: Two generic models, biological variation and sigma-metrics, are investigated. We selected variables in the models for Hb A(1c) and used data of external quality assurance/proficiency testing programs to evaluate the suitability of the models to set and evaluate quality targets within and between laboratories. RESULTS: In the biological variation model, 48% of individual laboratories and none of the 26 instrument groups met the minimum performance criterion. In the sigma-metrics model, with a total allowable error (TAE) set at 5 mmol/mol (0.46% NGSP), 77% of the individual laboratories and 12 of 26 instrument groups met the 2 sigma criterion. CONCLUSIONS: The biological variation and sigma-metrics models were demonstrated to be suitable for setting and evaluating quality targets within and between laboratories. The sigma-metrics model is more flexible, as both the TAE and the risk of failure can be adjusted to the situation for example, requirements related to diagnosis/monitoring or international authorities. With the aim of reaching (inter)national consensus on advice regarding quality targets for Hb A,5, the Task Force suggests the sigma-metrics model as the model of choice, with default values of 5 mmol/mol (0.46%) for TAE and risk levels of 2 sigma and 4 sigma for routine laboratories and laboratories performing clinical trials, respectively. These goals should serve as a starting point for discussion with international stakeholders in the field of diabetes. (C) 2015 American Association for Clinical Chemistry C1 [Weykamp, Cas] Locat Queen Beatrix Hosp, Dept Clin Chem, Winterswijk, Netherlands. [Weykamp, Cas] Locat Queen Beatrix Hosp, European Reference Lab, Winterswijk, Netherlands. [John, Garry] Norfolk & Norwich Univ Hosp, Norwich, Norfolk, England. [Gillery, Philippe] Univ Hosp Reims, Lab Pediat Biol & Res, Reims, France. [English, Emma] Univ Nottingham, Royal Derby Hosp, Sch Med, Derby, England. [Ji, Linong] Peking Univ, Peoples Hosp, Beijing 100871, Peoples R China. [Lenters-Westra, Erna] Isala Clin, Dept Clin Chem, Zwolle, Netherlands. [Lenters-Westra, Erna] European Reference Lab, Location Isala, Zwolle, Netherlands. [Little, Randie R.] Univ Missouri, Sch Med, Dept Pathol, Columbia, MO 65212 USA. [Little, Randie R.] Univ Missouri, Sch Med, Dept Child Hlth, Columbia, MO 65212 USA. [Roglic, Gojka] WHO, Dept Management Noncommunicable Dis, CH-1211 Geneva, Switzerland. [Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Takei, Izumi] Ichikawa Gen Hosp, Diabet & Endocrine Dept, Ichikawa, Japan. RP Weykamp, C (reprint author), Queen Beatrix Hosp, Dept Clin Chem, Beatrixpk 1, NL-7101 BN Winterswijk, Netherlands. EM c.w.weykamp@skbwinterswijk.nl FU Intramural Research Program of the NIH FX D.B. Sacks, Intramural Research Program of the NIH. NR 19 TC 16 Z9 16 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 MAY PY 2015 VL 61 IS 5 BP 752 EP 759 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CH2GR UT WOS:000353844200015 PM 25737535 ER PT J AU Rogers, T Lederman, RJ AF Rogers, Toby Lederman, Robert J. TI Interventional CMR: Clinical Applications and Future Directions SO CURRENT CARDIOLOGY REPORTS LA English DT Article DE Interventional cardiovascularMRI; Structural heart disease; MRI catheterization; Cardiac electrophysiology; Electrophysiology mapping and ablation.; Cardiovascular catheterization; Real-time MRI ID CONGENITAL HEART-DISEASE; REAL-TIME MRI; CARDIOVASCULAR MAGNETIC-RESONANCE; RADIOFREQUENCY ABLATION LESIONS; PULMONARY VASCULAR-RESISTANCE; ARTERY STENT PLACEMENT; CARDIAC-CATHETERIZATION; ANIMAL-MODEL; SWINE MODEL; IN-VIVO AB Interventional cardiovascular magnetic resonance (iCMR) promises to enable radiation-free catheterization procedures and to enhance contemporary image guidance for structural heart and electrophysiological interventions. However, clinical translation of exciting pre-clinical interventions has been limited by availability of devices that are safe to use in the magnetic resonance (MR) environment. We discuss challenges and solutions for clinical translation, including MR-conditional and MR-safe device design, and how to configure an interventional suite. We review the recent advances that have already enabled diagnostic MR right heart catheterization and simple electrophysiologic ablation to be performed in humans and explore future clinical applications. C1 [Rogers, Toby; Lederman, Robert J.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Lederman, RJ (reprint author), NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10,Room 2c713, Bethesda, MD 20892 USA. EM lederman@nih.gov OI lederman, robert/0000-0003-1202-6673; Rogers, Toby/0000-0002-6043-3137 FU Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health [Z01-HL005062] FX This work was supported by the Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health (Z01-HL005062). NR 84 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3782 EI 1534-3170 J9 CURR CARDIOL REP JI Curr. Cardiol. Rep. PD MAY PY 2015 VL 17 IS 5 AR 31 DI 10.1007/s11886-015-0580-1 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CG2XE UT WOS:000353138200001 PM 25894793 ER PT J AU Garriock, RJ Chalamalasetty, RB Kennedy, MW Canizales, LC Lewandoski, M Yamaguchi, TP AF Garriock, Robert J. Chalamalasetty, Ravindra B. Kennedy, Mark W. Canizales, Lauren C. Lewandoski, Mark Yamaguchi, Terry P. TI Lineage tracing of neuromesodermal progenitors reveals novel Wnt-dependent roles in trunk progenitor cell maintenance and differentiation SO DEVELOPMENT LA English DT Article DE Neural progenitor; Neuromesodermal progenitor; Wnt signaling; Brachyury; Paraxial mesoderm; Sox2 ID BETA-CATENIN GENE; AXIAL STEM-CELLS; PRIMITIVE STREAK; MOUSE EMBRYO; WNT/BETA-CATENIN; MESODERMAL TISSUES; AVIAN GASTRULATION; TAIL BUD; FATE; MICE AB In the development of the vertebrate body plan, Wnt3a is thought to promote the formation of paraxial mesodermal progenitors (PMPs) of the trunk region while suppressing neural specification. Recent lineage-tracing experiments have demonstrated that these trunk neural progenitors and PMPs derive from a common multipotent progenitor called the neuromesodermal progenitor (NMP). NMPs are known to reside in the anterior primitive streak (PS) region; however, the extent to which NMPs populate the PS and contribute to the vertebrate body plan, and the precise role that Wnt3a plays in regulating NMP self-renewal and differentiation are unclear. To address this, we used cell-specific markers (Sox2 and T) and tamoxifen-induced Cre recombinase-based lineage tracing to locate putative NMPs in vivo. We provide functional evidence for NMP location primarily in the epithelial PS, and to a lesser degree in the ingressed PS. Lineage-tracing studies in Wnt3a/beta-catenin signaling pathway mutants provide genetic evidence that trunk progenitors normally fated to enter the mesodermal germ layer can be redirected towards the neural lineage. These data, combined with previous PS lineage-tracing studies, support a model that epithelial anterior PS cells are Sox2(+)T(+) multipotent NMPs and form the bulk of neural progenitors and PMPs of the posterior trunk region. Finally, we find that Wnt3a/beta-catenin signaling directs trunk progenitors towards PMP fates; however, our data also suggest that Wnt3a positively supports a progenitor state for both mesodermal and neural progenitors. C1 [Garriock, Robert J.; Chalamalasetty, Ravindra B.; Kennedy, Mark W.; Canizales, Lauren C.; Lewandoski, Mark; Yamaguchi, Terry P.] NCI Frederick, Ctr Canc Res, Canc & Dev Biol Lab, Cell Signaling Vertebrate Dev Sect,NIH, Frederick, MD 21702 USA. RP Yamaguchi, TP (reprint author), NCI Frederick, Ctr Canc Res, Canc & Dev Biol Lab, Cell Signaling Vertebrate Dev Sect,NIH, Frederick, MD 21702 USA. EM yamagute@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 by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. Deposited in PMC for release after 12 months. NR 46 TC 15 Z9 16 U1 1 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD MAY 1 PY 2015 VL 142 IS 9 BP 1628 EP 1638 DI 10.1242/dev.111922 PG 11 WC Developmental Biology SC Developmental Biology GA CG8UY UT WOS:000353591300008 PM 25922526 ER PT J AU Anderson, AL Li, SH Markova, D Holmes, TH Chiang, N Kahn, R Campbell, J Dickerson, DL Galloway, GP Haning, W Roache, JD Stock, C Elkashef, AM AF Anderson, Ann L. Li, Shou-Hua Markova, Denka Holmes, Tyson H. Chiang, Nora Kahn, Roberta Campbell, Jan Dickerson, Daniel L. Galloway, Gantt P. Haning, William Roache, John D. Stock, Christopher Elkashef, Ahmed M. TI Bupropion for the treatment of methamphetamine dependence in non-daily users: A randomized, double-blind, placebo-controlled trial SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Bupropion; Methamphetamine; Substance-related disorders; Drug therapy; Medication adherence; Patient acuity ID ABUSE; INTERVIEW AB Aim: Bupropion was tested for efficacy to achieve methamphetamine (MA) abstinence in dependent, non-daily users. Methods: A randomized, double-blind, placebo-controlled trial, with 12-week treatment and 4-week follow-up, was conducted with 204 treatment-seeking participants having MA dependence per DSM-IV, who used MA on a less-than-daily basis. 104 were randomized to matched placebo and 100 to bupropion, sustained-release 150 mg, twice daily. Participants were seen three times weekly to obtain urine for MA and bupropion assays, study assessments, and thrice weekly, 90-min, group psychotherapy. There was no biomarker for placebo adherence. The primary outcome was achievement of abstinence throughout the last two weeks of treatment; 'success' requiring at least two urine samples during each of Weeks 11 and 12, and all samples MA-negative (<300 ng/mL). Results: Bupropion and placebo groups did not differ significantly in the percentage achieving abstinence for the last 2 weeks of treatment (chi-square, p = 0.32). Subgroup analysis of participants with lower baseline MA use (<= 18 of last 30 days before consent) also revealed no difference in success between groups (p = 0.73). Medication adherence per protocol (detectable bupropion, >5 ng/mL, in >= 50% of urine samples from Study Weeks 1-10 and >= 66% of urine samples from Weeks 11 to 12) was achieved by 47% of participants taking bupropion. Conclusions: These data indicate that bupropion did not increase abstinence in dependent participants who were using MA less-than-daily. Medication non-adherence was a limitation in this trial. Psychosocial therapy remains the mainstay of treatment for MA dependence. Further research on subgroups who may respond to bupropion may be warranted. Published by Elsevier Ireland Ltd. C1 [Anderson, Ann L.; Li, Shou-Hua; Chiang, Nora; Kahn, Roberta] NIDA, NIH, Div Pharmacotherapies & Med Consequences, Bethesda, MD 20892 USA. [Markova, Denka] Medivation Inc, San Francisco, CA USA. [Holmes, Tyson H.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford Ctr Sleep Sci & Med, Stanford, CA 94305 USA. [Campbell, Jan] Univ Kansas, Kansas City, KS USA. [Dickerson, Daniel L.] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA USA. [Galloway, Gantt P.] St Lukes Hosp, San Francisco, CA USA. [Haning, William] Univ Hawaii, Honolulu, HI 96822 USA. [Roache, John D.] UTX, Hlth Sci Ctr, San Antonio, TX USA. [Stock, Christopher] VA Hlth Care Syst, Salt Lake City, UT USA. [Elkashef, Ahmed M.] Natl Rehabil Ctr, Abu Dhabi, U Arab Emirates. RP Anderson, AL (reprint author), NIDA, NIH, DPMCDA, 6001 Execut Blvd,Rm 4149, Bethesda, MD 20892 USA. EM aa135m@nih.gov FU Nat'l Institutes of Health - Nat'l Institute on Drug Abuse [N01DA-05-8857]; NIDA through the Department of Veterans Affairs [1 Y01-DA-40032] FX This study was funded by Nat'l Institutes of Health - Nat'l Institute on Drug Abuse contract: N01DA-05-8857. NIDA had a major role in study design, analysis and interpretation of the data, and writing and submitting this manuscript for publication.; THH received partial salary support from NIDA through the Department of Veterans Affairs Cooperative Studies Program (Interagency Agreement) 1 Y01-DA-40032. NR 19 TC 8 Z9 8 U1 2 U2 8 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 MAY 1 PY 2015 VL 150 BP 170 EP 174 DI 10.1016/j.drugalcdep.2015.01.036 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CG8YF UT WOS:000353600900023 PM 25818061 ER PT J AU He, S Bergman, J Zhang, YM Weusten, B Xue, LY Qin, XM Dou, LZ Liu, Y Fleischer, D Lu, N Dawsey, SM Wang, GQ AF He, Shun Bergman, Jacques Zhang, Yueming Weusten, Bas Xue, Liyan Qin, Xiumin Dou, Lizhou Liu, Yong Fleischer, David Lu, Ning Dawsey, Sanford M. Wang, Gui-Qi TI Endoscopic radiofrequency ablation for early esophageal squamous cell neoplasia: report of safety and effectiveness from a large prospective trial SO ENDOSCOPY LA English DT Article ID GRADE INTRAEPITHELIAL NEOPLASIA; SUBMUCOSAL DISSECTION; MUCOSAL RESECTION; BARRETTS-ESOPHAGUS; CARCINOMA; CANCER; DYSPLASIA; OUTCOMES; CHINA; LINXIAN AB Background and study aims: Endoscopic radiofrequency ablation (RFA) is an established therapy for Barrett's esophagus. Preliminary reports, limited by low patient numbers, also suggest a possible role for RFA in early esophageal squamous cell neoplasia (ESCN). The aim of this study was to evaluate the safety and effectiveness of RFA for early ESCN (moderate/high grade intraepithelial neoplasia [MGIN/HGIN] and early flat-type esophageal squamous cell carcinoma [ESCC]). Patients and methods: This prospective cohort study included patients with at least one flat (type 0-IIb) unstained lesion (USL) on Lugol's chromoendoscopy and a consensus diagnosis of MGIN, HGIN, or early ESCC. RFA was used at baseline to treat all USLs, and then biopsy (and focal RFA if USL persisted) was performed every 3 months until all biopsies were negative for MGIN, HGIN, and ESCC. The main outcome measurements were complete response at 3 and 12 months (absence of MGIN, HGIN, and ESCC), neoplastic progression, and adverse events. Results: A total of 96 patients participated (MGIN 45, HGIN 42, early ESCC 9). At 3 and 12 months, 73% (70/96) and 84% (81/96), respectively, showed a complete response. Two patients (2 %) progressed (MGIN to HGIN; HGIN to T1m2 ESCC); both were treated endoscopically and achieved complete response. Stricture occurred in 20 patients (21 %), all after circumferential RFA. Lugol's + RFA 12J/cm(2) (single application, no cleaning) was the favored baseline circumferential RFA technique (82% 12-month complete response [14/17], 6% stricture [6/17]). Conclusion: In patients with early ESCN, RFA was associated with a high complete response rate and an acceptable safety profile. C1 [He, Shun; Zhang, Yueming; Qin, Xiumin; Dou, Lizhou; Liu, Yong; Wang, Gui-Qi] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Endoscopy, Beijing 100021, Peoples R China. [He, Shun; Zhang, Yueming; Xue, Liyan; Qin, Xiumin; Dou, Lizhou; Liu, Yong; Lu, Ning; Wang, Gui-Qi] Peking Union Med Coll, Beijing 100021, Peoples R China. [Bergman, Jacques; Weusten, Bas] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, NL-1105 AZ Amsterdam, Netherlands. [Weusten, Bas] St Antonius Hosp, Dept Gastroenterol, Nieuwegein, Netherlands. [Xue, Liyan; Lu, Ning] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Pathol, Beijing 100021, Peoples R China. [Fleischer, David] Mayo Clin, Div Gastroenterol & Hepatol, Scottsdale, AZ USA. [Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Wang, GQ (reprint author), Chinese Acad Med Sci, Canc Inst & Hosp, Dept Endoscopy, 17 Panjiayuan, Beijing 100021, Peoples R China. EM wangguiq@126.com FU Covidien GI Solutions; Olympus Medical FX Dr. Bergman has received medical supplies for study purposes and unrestricted grant aid for training programs from Covidien GI Solutions (formerly BARRX Medical). He has also received an unrestricted grant from Olympus Medical. Dr. Wang has received medical supplies for study purposes from Covidien GI Solutions (formerly BARRX Medical). NR 39 TC 5 Z9 7 U1 1 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X EI 1438-8812 J9 ENDOSCOPY JI Endoscopy PD MAY PY 2015 VL 47 IS 5 BP 398 EP 408 DI 10.1055/s-0034-1391285 PG 11 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA CG8MP UT WOS:000353562400003 PM 25668428 ER PT J AU Kono, M Proia, RL AF Kono, Mari Proia, Richard L. TI Imaging S1P1 activation in vivo SO EXPERIMENTAL CELL RESEARCH LA English DT Review DE Signaling; Sphingolipid; Sphingosine-1-phosphate; GPCR; Inflammation; Homeostasis ID PROTEIN-COUPLED RECEPTOR; PERSISTENT STAT3 ACTIVATION; MULTIPLE-SCLEROSIS; ENDOTHELIAL-CELLS; VASCULAR MATURATION; FINGOLIMOD FTY720; SPHINGOSINE-1-PHOSPHATE; EXPRESSION; MICE; INFLAMMATION AB Sphingosine-1-phosphate receptor 1 (S1P1) is a G protein-coupled receptor that is activated by the sphingolipid ligand sphingosine-1-phosphate (S1P). S1P1 is widely expressed across tissues and, when activated, has broad functions in the immune, vascular and nervous systems. In several diseases in which inflammation plays a critical role, S1P1 activation has been found to be involved in pathogenesis. However, the details of S1P1 activation in vivo under different physiologic conditions are not well understood. Here we describe how a new in vivo methodology to identify S1P1 activation has helped increase understanding of the manner in which this signaling molecule functions both in homeostasis and during inflammation. Published by Elsevier Inc. C1 [Kono, Mari; Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Proia, RL (reprint author), NIDDK, Genet Dev & Dis Branch, Bldg 10,Room 9D-06,10 Ctr DR MSC 1821, Bethesda, MD 20892 USA. EM richardp@intra.niddk.nih.gov FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases FX We thank Linda Raab for editing and helpful comments on the manuscript. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. NR 29 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 EI 1090-2422 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 1 PY 2015 VL 333 IS 2 BP 178 EP 182 DI 10.1016/j.yexcr.2014.11.023 PG 5 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CG9UR UT WOS:000353666100004 PM 25498971 ER PT J AU Liu, SX Wang, Y Worley, PF Mattson, MP Gaiano, N AF Liu, Shuxi Wang, Yue Worley, Paul F. Mattson, Mark P. Gaiano, Nicholas TI The Canonical Notch Pathway Effector RBP-J Regulates Neuronal Plasticity and Expression of GABA Transporters in Hippocampal Networks SO HIPPOCAMPUS LA English DT Article DE RBP-J; canonical Notch signaling; GABA transporter; neuronal plasticity; learning and memory ID SYNAPTIC PLASTICITY; MOUSE-BRAIN; SIGNALING PATHWAY; GENE KNOCKOUT; MEMORY; LOCALIZATION; RECOGNITION; CELLS; GAT-3 AB Activation of the Notch pathway in neurons is essential for learning and memory in various species from invertebrates to mammals. However, it remains unclear how Notch signaling regulates neuronal plasticity, and whether the transcriptional regulator and canonical pathway effector RBP-J plays a role. Here, we report that conditional disruption of RBP-J in the postnatal hippocampus leads to defects in long-term potentiation, long-term depression, and in learning and memory. Using gene expression profiling and chromatin immunoprecipitation, we identified two GABA transporters, GAT2 and BGT1, as putative Notch/RBP-J pathway targets, which may function downstream of RBP-J to limit the accumulation of GABA in the Schaffer collateral pathway. Our results reveal an essential role for canonical Notch/RBP-J signaling in hippocampal synaptic plasticity and suggest that role, at least in part, is mediated by the regulation of GABAergic signaling. (c) 2014 Wiley Periodicals, Inc. C1 [Liu, Shuxi; Gaiano, Nicholas] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Neuroregenerat Program, Baltimore, MD USA. [Liu, Shuxi; Worley, Paul F.; Gaiano, Nicholas] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Wang, Yue; Mattson, Mark P.] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. [Worley, Paul F.; Mattson, Mark P.; Gaiano, Nicholas] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Gaiano, Nicholas] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. RP Liu, SX (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. EM shuxi.liu@nih.hhs.gov; Mark.mattson@nih.gov FU Institute for Cell Engineering at Johns Hopkins University; Young Investigator Award from the Brain and Behavior Research Foundation; James S. McDonnell Foundation; National Institute of Mental Health; Intramural Research Program of the National Institute on Aging, National Institutes of Health FX Grant sponsor: Institute for Cell Engineering at Johns Hopkins University (N.G.), a Young Investigator Award from the Brain and Behavior Research Foundation (N.G.), the James S. McDonnell Foundation (N.G.), the National Institute of Mental Health (P.W.), and the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 30 TC 3 Z9 3 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1050-9631 EI 1098-1063 J9 HIPPOCAMPUS JI Hippocampus PD MAY PY 2015 VL 25 IS 5 BP 670 EP 678 DI 10.1002/hipo.22402 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CH4BF UT WOS:000353975200011 PM 25515406 ER PT J AU Liu, Q Du, X Hong, XF Li, TM Zheng, B He, L Wang, YN Otto, M Li, M AF Liu, Qian Du, Xin Hong, Xufen Li, Tianming Zheng, Bing He, Lei Wang, Yanan Otto, Michael Li, Min TI Targeting Surface Protein SasX by Active and Passive Vaccination To Reduce Staphylococcus aureus Colonization and Infection SO INFECTION AND IMMUNITY LA English DT Article ID NASAL CARRIAGE; VIRULENCE DETERMINANT; DISEASE; EXPRESSION; VARIANT; ALPHA AB SasX is a recently described surface protein of Staphylococcus aureus that is linked to the epidemic success of hospital-associated methicillin-resistant clones, in particular in Asia. It enhances nasal colonization and virulence in skin and lung infection models. Here, we evaluated the potential of SasX as a vaccine component in passive and active immunization efforts using mouse infection models. We found that SasX induced a specific immune response predominantly based on IgG1 antibodies. Active immunization with recombinant SasX or passive immunization with rabbit polyclonal anti-SasX IgG significantly decreased the size of lesions caused by Staphylococcus aureus in a skin infection model. Furthermore, active immunization reduced acute lung injury in a lung infection model. Moreover, active or passive immunization significantly reduced Staphylococcus aureus colonization in a nasal colonization model. Finally, anti-SasX IgG enhanced the susceptibility of Staphylococcus aureus to killing by human neutrophils. We conclude that SasX is a potential target for therapeutics or vaccines designed to moderate colonization and infection by sasX-positive epidemic strains of Staphylococcus aureus. C1 [Liu, Qian; Li, Tianming; Zheng, Bing; He, Lei; Wang, Yanan; Li, Min] Shanghai Jiao Tong Univ, Dept Lab Med, Renji Hosp, Sch Med, Shanghai 200030, Peoples R China. [Du, Xin; Hong, Xufen] Fudan Univ, Dept Lab Med, Huashan Hosp, Shanghai Med Coll, Shanghai 200433, Peoples R China. [Wang, Yanan] NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. RP Otto, M (reprint author), NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM motto@niaid.nih.gov; ruth_limin@126.com OI Otto, Michael/0000-0002-2222-4115 FU National Natural Science Foundation of China [81322025, 81171623, 81371875]; Shanghai Shuguang Talent Project [12SG03]; Shanghai Committee of Science and Technology, China [14140901000]; Foundation for Innovative Research Groups of the National Natural Science Foundation of China [81421001]; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This study was supported by the National Natural Science Foundation of China (grants 81322025, 81171623, and 81371875), Shanghai Shuguang Talent Project (12SG03), the Shanghai Committee of Science and Technology, China (14140901000), and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (grant no. 81421001) (to M.L.) and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, the National Institutes of Health (to M.O.). NR 27 TC 3 Z9 4 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2015 VL 83 IS 5 BP 2168 EP 2174 DI 10.1128/IAI.02951-14 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CG0TJ UT WOS:000352982600040 PM 25776748 ER PT J AU Winnenburg, R Sorbello, A Bodenreider, O AF Winnenburg, Rainer Sorbello, Alfred Bodenreider, Olivier TI Exploring adverse drug events at the class level SO JOURNAL OF BIOMEDICAL SEMANTICS LA English DT Article DE Adverse drug events; Drug classes; Anatomical Therapeutic Chemical (ATC) drug classification system; Class effect; Heat maps; Pharmacovigilance ID REPORTING SYSTEM AB Background: While the association between a drug and an adverse event (ADE) is generally detected at the level of individual drugs, ADEs are often discussed at the class level, i.e., at the level of pharmacologic classes (e.g., in drug labels). We propose two approaches, one visual and one computational, to exploring the contribution of individual drugs to the class signal. Methods: Having established a dataset of ADEs from MEDLINE, we aggregate drugs into ATC classes and ADEs into high-level MeSH terms. We compute statistical associations between drugs and ADEs at the drug level and at the class level. Finally, we visualize the signals at increasing levels of resolution using heat maps. We also automate the exploration of drug-ADE associations at the class level using clustering techniques. Results: Using our visual approach, we were able to uncover known associations, e.g., between fluoroquinolones and tendon injuries, and between statins and rhabdomyolysis. Using our computational approach, we systematically analyzed 488 associations between a drug class and an ADE. Conclusions: The findings gained from our exploratory techniques should be of interest to the curators of ADE repositories and drug safety professionals. Our approach can be applied to different drug-ADE datasets, using different drug classification systems and different signal detection algorithms. C1 [Winnenburg, Rainer] Stanford Univ, Ctr Biomed Informat Res, Stanford, CA 94305 USA. [Sorbello, Alfred] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Bodenreider, Olivier] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, Bethesda, MD 20892 USA. RP Bodenreider, O (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, Bethesda, MD 20892 USA. EM obodenreider@mail.nih.gov FU Intramural Research Program of the NIH, National Library of Medicine (NLM); US Food and Drug Administration (FDA) through the Center for Drug Evaluation and Research (CDER) Critical Path Program [XLM12011 001]; Office of Translational Sciences at CDER; U.S. Department of Energy; National Library of Medicine FX A preliminary version of this work was presented to the Vaccine and Drug Ontology Studies (VDOS-2014) workshop. This work was supported by the Intramural Research Program of the NIH, National Library of Medicine (NLM). This work also received support from the US Food and Drug Administration (FDA) through the Center for Drug Evaluation and Research (CDER) Critical Path Program [interagency agreement with NLM (XLM12011 001)] and from the Office of Translational Sciences at CDER. While conducting this research, RW was supported by an appointment to the NLM Research Participation Program administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the National Library of Medicine. The authors want to thank Ana Szarfman, Rave Harpaz and Anna Ripple for useful discussions. NR 24 TC 2 Z9 2 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2041-1480 J9 J BIOMED SEMANT JI J. Biomed. Semant. PD MAY 1 PY 2015 VL 6 AR 18 DI 10.1186/s13326-015-0017-1 PG 10 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA CH0BP UT WOS:000353684200001 PM 25937884 ER PT J AU Dubey, JP Sykes, JE Shelton, GD Sharp, N Verma, SK Calero-Bernal, R Viviano, J Sundar, N Khan, A Grigg, ME AF Dubey, Jitender P. Sykes, Jane E. Shelton, G. Diane Sharp, Nick Verma, Shiv K. Calero-Bernal, Rafael Viviano, Jenifer Sundar, Natarajan Khan, Asis Grigg, Michael E. TI Sarcocystis caninum and Sarcocystis svanai n. spp. (Apicomplexa: Sarcocystidae) Associated with Severe Myositis and Hepatitis in the Domestic Dog (Canis familiaris) SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE Canada; dog; USA ID BEARS URSUS-MARITIMUS; MUSCULAR SARCOCYSTOSIS; NEURONA; ENCEPHALITIS; INFECTION; SCHIZONTS; PARASITE AB There are several reports of Sarcocystis sarcocysts in muscles of dogs, but these species have not been named. Additionally, there are two reports of Sarcocystis neurona in dogs. Here, we propose two new names, Sarcocystis caninum, and Sarcocystis svanai for sarcocysts associated with clinical muscular sarcocystosis in four domestic dogs (Canis familiaris), one each from Montana and Colorado in the USA, and two from British Columbia, Canada. Only the sarcocyst stage was identified. Most of the sarcocysts identified were S. caninum. Sarcocysts were studied using light microscopy, transmission electron microscopy (TEM), and polymerase chain reaction. Based on collective results two new species, S. caninum and S. svanai were designated. Sarcocystis caninum and S. svanai were structurally distinct. Sarcocystis caninum sarcocysts were up to 1.2mm long and up to 75m wide. By light microscopy, the sarcocyst wall was relatively thin and smooth. By TEM, the sarcocyst wall was type 9, 1-2m thick, and contained villar protrusions that lacked microtubules. Bradyzoites in sections were 7-9m long. Sarcocysts of S. svanai were few and were identified by TEM. Sarcocystis svanai sarcocysts were type 1, thin walled (<0.5m), and the wall lacked villar protrusions but had tiny blebs that did not invaginate. DNA was extracted either from infected frozen muscle biopsies or formalin-fixed paraffin-embedded sections. Dogs were either singly infected with S. caninum or multiply co-infected with S. caninum and S. svanai (the result of a mixed infection) based on multilocus DNA sequencing and morphology. BLASTn analysis established that the sarcocysts identified in these dogs were similar to, but not identical to Sarcocystis canis or Sarcocystis arctosi, parasites found to infect polar bears (Ursus maritimus) or brown bears (Ursus arctosi), respectively. However, the S. caninum sequence showed 100% identify over the 18S rRNA region sequenced to that of S. arctica, a parasite known to infect Arctic foxes (Vulpes lagopus). C1 [Dubey, Jitender P.; Verma, Shiv K.; Calero-Bernal, Rafael] ARS, Anim Parasit Dis Lab, USDA, Beltsville Agr Res Ctr, Beltsville, MD 20705 USA. [Sykes, Jane E.] Univ Calif Davis, Sch Vet Med, Dept Med & Epidemiol, Davis, CA 95616 USA. [Shelton, G. Diane] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Sharp, Nick] Canada West Vet Specialists, Vancouver, BC V6R 1E5, Canada. [Viviano, Jenifer] US Army, Joint Pathol Ctr, Vet Pathol Serv, Silver Spring, MD 20910 USA. [Sundar, Natarajan; Khan, Asis; Grigg, Michael E.] NIAID, Mol Parasitol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Dubey, JP (reprint author), BARC, Anim Parasit Dis Lab, USDA, Bldg 1001, Beltsville, MD 20705 USA. EM jitender.dubey@ars.usda.gov FU NIH; NIAID; Department of Employment and Innovation of the Regional Government of Extremadura, Spain [PO12010]; European Social Fund [PO12010] FX The authors thank Dr. Eric Hoberg for his helpful suggestions concerning taxonomy, and Mr. Efrain Perez, Joint Pathology Center, Veterinary Services, U.S. Army, Silver Spring, Maryland for excellent technical help with electron microscopy. This study was financially support in part by the Intramural Research Program of the NIH and NIAID. M.E.G. is a scholar of the Canadian Institute for Advanced Research Integrated Microbial Biodiversity Program.; R. Calero-Bernal is a postdoctoral fellow (ref. PO12010) funded by the Department of Employment and Innovation of the Regional Government of Extremadura, Spain and the European Social Fund. NR 24 TC 2 Z9 2 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5234 EI 1550-7408 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD MAY-JUN PY 2015 VL 62 IS 3 BP 307 EP 317 DI 10.1111/jeu.12182 PG 11 WC Microbiology SC Microbiology GA CG8IQ UT WOS:000353551300004 PM 25256157 ER PT J AU Gai, ND Butman, JA AF Gai, Neville D. Butman, John A. TI Reduced Scan Time Three-Dimensional FLAIR Using Modulated Inversion and Repetition Time SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE 3D FLAIR; modulated repetition time; modulated inversion time; scan time reduction; variable repetition time ID REFOCUSING FLIP ANGLES; SEQUENCES; OPTIMIZATION; BRAIN; TESLA; T1 AB BackgroundThe purpose of this study is to design and evaluate a new reduced scan time three-dimensional (3D) FLuid Attenuated Inversion Recovery (FLAIR) sequence. MethodsThe 3D FLAIR sequence was modified so that the repetition time was modulated in a predetermined smooth manner (3D mFLAIR). Inversion times were adjusted accordingly to maintain cerebrospinal fluid (CSF) suppression. Simulations were performed to determine SNR for gray matter (GM), white matter (WM), and CSF. Fourteen volunteers were imaged using the modified and product sequence. SNR measurements were performed in GM, WM, and CSF. Mean value and the 95% confidence interval ([CI]) were assessed. Scan time for the 3D FLAIR and 3D mFLAIR sequences was measured. ResultsThere was no statistically significant difference in the SNR measured in GM (P value=0.5; mean SNR=42.8 [CI]: 38.2-45.5 versus 42.2 [CI]: 38.3-46.1 for 3D FLAIR and 3D mFLAIR, respectively) and WM (P value=0.25; mean SNR=32.1 [CI]: 30.3-33.8 versus 32.9 [CI]: 31.1-34.7). Scan time reduction greater than 30% was achieved for the given parameter set with the 3D mFLAIR sequence. ConclusionScan time for 3D FLAIR can be effectively reduced by modulating repetition and inversion time in a predetermined manner while maintaining the SNR and CNR of a constant TR sequence. J. Magn. Reson. Imaging 2015;41:1440-1446. (c) 2014 Wiley Periodicals, Inc. C1 [Gai, Neville D.; Butman, John A.] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Gai, ND (reprint author), NIH, Radiol & Imaging Sci RAD&IS, Ctr Clin, 9000 Rockville Pike,Bldg 10 Room 1C502, Bethesda, MD 20892 USA. EM gaind@cc.nih.gov RI Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 FU Intramural Research Program of the NIH Clinical Center FX This work was supported by the Intramural Research Program of the NIH Clinical Center. NR 12 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 EI 1522-2586 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD MAY PY 2015 VL 41 IS 5 BP 1440 EP 1446 DI 10.1002/jmri.24679 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CG9ND UT WOS:000353641600032 PM 24979311 ER PT J AU Gold, B Cankovic, M Furtado, LV Meier, F Gocke, CD AF Gold, Bert Cankovic, Milena Furtado, Larissa V. Meier, Frederick Gocke, Christopher D. TI Do Circulating Tumor Cells, Exosomes, and Circulating Tumor Nucleic Acids Have Clinical Utility? A Report of the Association for Molecular Pathology SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID LUNG-CANCER PATIENTS; METASTATIC BREAST-CANCER; K-RAS MUTATIONS; RESISTANT PROSTATE-CANCER; PRIMARY COLORECTAL CANCERS; SERUM MICRORNA EXPRESSION; PLASMA DNA; PERIPHERAL-BLOOD; PANCREATIC-CANCER; MICROSATELLITE ALTERATIONS AB Diagnosing and screening for tumors through noninvasive means represent an important paradigm shift in precision medicine. In contrast to tissue biopsy, detection of circulating tumor cells (CTCs) and circulating tumor nucleic acids provides a minimally invasive method for predictive and prognostic marker detection. This allows early and serial assessment of metastatic disease, including follow-up during remission, characterization of treatment effects, and clonal evolution. Isolation and characterization of CTCs and circulating tumor DNA (ctDNA) are likely to improve cancer diagnosis, treatment, and minimal residual disease monitoring. However, more trials are required to validate the clinical utility of precise molecular markers for a variety of tumor types. This review focuses on the clinical utility of CTCs and ctDNA testing in patients with solid tumors, including somatic and epigenetic alterations that can be detected. A comparison of methods used to isolate and detect CTCs and some of the intricacies of the characterization of the ctDNA are also provided. C1 [Gold, Bert; Cankovic, Milena; Furtado, Larissa V.; Meier, Frederick; Gocke, Christopher D.] Circulating Tumor Cells Working Grp, Clin Practice Comm, Associat Mol Pathol, Bethesda, MD USA. [Gold, Bert] NIH, Ctr Canc Res, Frederick, MD 21702 USA. [Cankovic, Milena; Meier, Frederick] Henry Ford Hosp, Dept Pathol, Detroit, MI 48202 USA. [Furtado, Larissa V.] Univ Chicago, Med Ctr, Dept Pathol, Chicago, IL 60637 USA. [Gocke, Christopher D.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Gold, B (reprint author), NIH, Ctr Canc Res, 1050 Boyles St, Frederick, MD 21702 USA. EM bert.gold@nih.gov FU Association for Molecular Pathology; Intramural Research Program of the National Cancer Institute, NIH FX Supported in part by the Association for Molecular Pathology and the Intramural Research Program of the National Cancer Institute, NIH. NR 221 TC 21 Z9 22 U1 4 U2 36 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD MAY PY 2015 VL 17 IS 3 BP 209 EP 224 DI 10.1016/j.jmoldx.2015.02.001 PG 16 WC Pathology SC Pathology GA CH2GO UT WOS:000353843900001 PM 25908243 ER PT J AU Janssen, I Millo, C Ling, A Chen, C Herscovitch, P Pacak, K AF Janssen, I. Millo, C. Ling, A. Chen, C. Herscovitch, P. Pacak, K. TI Comparison of Ga-68-DOTATATE PET/CT with other functional imaging studies in head and neck paragangliomas: preliminary results SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 3rd Theranostics World Congress on Gallium-68 and PRRT CY MAR 12-14, 2015 CL Johns Hopkins Med Campus, Baltimore, MD SP Soc Nucl Med & Mol Imaging, Johns Hopkins Univ HO Johns Hopkins Med Campus C1 [Janssen, I.; Millo, C.; Ling, A.; Chen, C.; Herscovitch, P.; Pacak, K.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2015 VL 56 SU 2 MA 34 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CH1XO UT WOS:000353816700035 ER PT J AU Miljkovic, MD Emuron, D Rhodes, L Abraham, J Miller, K AF Miljkovic, Milos D. Emuron, Dennis Rhodes, Lori Abraham, Joseph Miller, Kenneth TI "Allow Natural Death" versus "Do Not Resuscitate": What Do Patients with Advanced Cancer Choose? SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; LIFE; CARE; COMMUNICATION; VIDEO AB Background: Many patients with advanced cancer at our hospital request full resuscitative efforts at the end of life. We assessed the knowledge and attitudes of these patients towards end-of-life (EOL) care, and their preferences about "Do Not Resuscitate" (DNR), "Allow Natural Death" (AND), and "full code" orders. Methods: The first 100 consenting adult patients with advanced cancer were surveyed regarding their diagnosis, prognosis, and attitudes about critical care and resuscitation. They were then presented with hypothetical scenarios in which a decision on their code status had to be made if they had one year, six months, or one month left to live. Half were given a choice between being "full code" and "DNR," and half could choose between "full code" and "AND." Results: All 93 of the participants who completed the survey were considered by their attending physician to have a terminal illness, but only 42% of these interviewees believed they were terminally ill. In addition, only 25% of participants thought that their primary oncologist knew their EOL wishes. Participants were equally likely to choose either of the "no code" options in all hypothetical scenarios (p>0.54), regardless of age, sex, race, type of cancer, education, or income level. A similar proportion of patients who had a living will chose "AND" and "DNR" orders instead of "full code" in all the scenarios (47%-74% and 63%-71%). In contrast, among patients who did not have a living will, 52% chose "DNR," while 19% opted for "AND." Conclusions: We hypothesized that "AND" orders may be more acceptable to patients with advanced cancer, but there was no statistically significant difference in acceptability between "AND" and "DNR" orders. C1 [Miljkovic, Milos D.] US Naval Hosp, NCI, Med Oncol Serv, Bethesda, MD 20814 USA. [Emuron, Dennis] Sinai Hosp, Dept Internal Med, Baltimore, MD 21215 USA. [Rhodes, Lori] Sinai Hosp, Alvin & Lois Lapidus Canc Inst, Baltimore, MD 21215 USA. [Abraham, Joseph] Apex Epidemiol, Baltimore, MD USA. [Miller, Kenneth] Sinai Hosp, Alvin & Lois Lapidus Canc Inst, Div Hematol Med Oncol, Baltimore, MD 21215 USA. RP Miljkovic, MD (reprint author), US Naval Hosp, NCI, Med Oncol Serv, 10 Ctr Dr,Room 12N226, Bethesda, MD 20814 USA. EM milos@miljko.org RI Miljkovic, Milos/F-7685-2011 OI Miljkovic, Milos/0000-0001-5848-6320 NR 14 TC 3 Z9 3 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD MAY 1 PY 2015 VL 18 IS 5 BP 457 EP 460 DI 10.1089/jpm.2014.0369 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CH0LC UT WOS:000353710300013 PM 25825919 ER PT J AU Lowitz, J Keil, MF AF Lowitz, Judith Keil, Margaret F. TI Cushing Syndrome: Establishing a Timely Diagnosis SO JOURNAL OF PEDIATRIC NURSING-NURSING CARE OF CHILDREN & FAMILIES LA English DT Editorial Material ID QUALITY-OF-LIFE; CHILDREN; ADOLESCENTS; CURE C1 [Keil, Margaret F.] NIH, Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. RP Keil, MF (reprint author), NIH, Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. EM keilm@mail.nih.gov FU Intramural Research Program of National Institutes of Health, Eunice Kennedy Shriver NICHD FX This work was supported in part by the Intramural Research Program of National Institutes of Health, Eunice Kennedy Shriver NICHD. We thank Kathy Feigenbaum, Carol VanRyzin, and Dr. Barbara Jordan for their review and comments. NR 10 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0882-5963 J9 J PEDIATR NURS JI J. Pediatr. Nurs. PD MAY-JUN PY 2015 VL 30 IS 3 BP 528 EP 530 DI 10.1016/j.pedn.2015.02.006 PG 3 WC Nursing; Pediatrics SC Nursing; Pediatrics GA CH2BL UT WOS:000353829000018 PM 25724858 ER PT J AU Davis, AS Gantz, MG Do, B Shankaran, S Hamrick, SEG Kennedy, KA Tyson, JE Chalak, LF Laptook, AR Goldstein, RF Hintz, SR Das, A Higgins, RD Ball, MB Hale, EC Van Meurs, KP AF Davis, A. S. Gantz, M. G. Do, B. Shankaran, S. Hamrick, S. E. G. Kennedy, K. A. Tyson, J. E. Chalak, L. F. Laptook, A. R. Goldstein, R. F. Hintz, S. R. Das, A. Higgins, R. D. Ball, M. B. Hale, E. C. Van Meurs, K. P. CA Eunice Kennedy Shriver Natl Inst C Human Dev Neonatal Res Network TI Serial aEEG recordings in a cohort of extremely preterm infants: feasibility and safety SO JOURNAL OF PERINATOLOGY LA English DT Article ID AMPLITUDE-INTEGRATED ELECTROENCEPHALOGRAPHY; HYPOXIC-ISCHEMIC ENCEPHALOPATHY; BACKGROUND PATTERNS; BRAIN-FUNCTION; 1ST WEEK; TERM; PREDICTS; BIRTH; LIFE; HEMORRHAGE AB OBJECTIVE: Amplitude-integrated electroencephalography (aEEG) monitoring is increasing in the neonatal population, but the safety and feasibility of performing aEEG in extremely preterm infants have not been systematically evaluated. STUDY DESIGN: Inborn infants 230/7 to 286/7 weeks gestation or birth weight 401 to 1000 g were eligible. Serial, 6-h aEEG recordings were obtained from first week of life until 36 weeks postmenstrual age. Adverse events were documented, and surveys evaluated the impact of the aEEGs on routine care. Success of performing aEEGs according to protocol and aEEG quality were assessed. RESULT: A total of 102 infants were enrolled, with 755 recordings performed. 83% of recordings were performed according to schedule, and 96% were without adverse event. Bedside nurses reported no interference with routine care for 89% of recordings. 92% of recordings had acceptable signal quality. CONCLUSION: Serial aEEG monitoring is safe in preterm infants, with few adverse events and general acceptance by nursing staff. C1 [Davis, A. S.; Hintz, S. R.; Ball, M. B.; Van Meurs, K. P.] Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med, Palo Alto, CA 94304 USA. [Davis, A. S.; Hintz, S. R.; Ball, M. B.; Van Meurs, K. P.] Lucile Packard Childrens Hosp, Palo Alto, CA 94304 USA. [Gantz, M. G.; Do, B.] RTI Int, Social Stat & Environm Sci Unit, Res Triangle Pk, NC USA. [Shankaran, S.] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [Hamrick, S. E. G.; Hale, E. C.] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA. [Kennedy, K. A.; Tyson, J. E.] Univ Texas Houston, Med Sch Houston, Dept Pediat, Houston, TX USA. [Chalak, L. F.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Laptook, A. R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA. [Goldstein, R. F.] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Das, A.] RTI Int, Social Stat & Environm Sci Unit, Rockville, MD USA. [Higgins, R. D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Inst Hlth, Bethesda, MD USA. RP Davis, AS (reprint author), Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med, 750 Welch Rd,Suite 315, Palo Alto, CA 94304 USA. EM alexisdavismd@gmail.com FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX We are indebted to our medical and nursing colleagues and to the infants and their parents who agreed to take part in this study. A complete list of investigators who participated in this study are listed in the Appendix. The National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development provided grant support for this study. NR 35 TC 0 Z9 0 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0743-8346 EI 1476-5543 J9 J PERINATOL JI J. Perinatol. PD MAY PY 2015 VL 35 IS 5 BP 373 EP 378 DI 10.1038/jp.2014.217 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA CG8NP UT WOS:000353565200013 PM 25474559 ER PT J AU O'Connor, GM Vivian, JP Gostick, E Pymm, P Lafont, BAP Price, DA Rossjohn, J Brooks, AG McVicar, DW AF O'Connor, Geraldine M. Vivian, Julian P. Gostick, Emma Pymm, Phillip Lafont, Bernard A. P. Price, David A. Rossjohn, Jamie Brooks, Andrew G. McVicar, Daniel W. TI Peptide-Dependent Recognition of HLA-B*57:01 by KIR3DS1 SO JOURNAL OF VIROLOGY LA English DT Article ID NATURAL-KILLER-CELL; IMMUNOGLOBULIN-LIKE RECEPTOR; HLA-B; CRYSTAL-STRUCTURE; HIV-INFECTION; BW4 EPITOPE; NK CELLS; BINDING; COMPLEX; KIR AB Killer cell immunoglobulin-like receptors (KIRs) play an important role in the activation of natural killer (NK) cells, which in turn contribute to the effective immune control of many viral infections. In the context of HIV infection, the closely related KIR3DL1 and KIR3DS1 molecules, in particular, have been associated with disease outcome. Inhibitory signals via KIR3DL1 are disrupted by downregulation of HLA class I ligands on the infected cell surface and can also be impacted by changes in the presented peptide repertoire. In contrast, the activatory ligands for KIR3DS1 remain obscure. We used a structure-driven approach to define the characteristics of HLA class I-restricted peptides that interact with KIR3DL1 and KIR3DS1. In the case of HLAB*57:01, we used this knowledge to identify bona fide HIV-derived peptide epitopes with similar properties. Two such peptides facilitated productive interactions between HLA-B* 57:01 and KIR3DS1. These data reveal the presence of KIR3DS1 ligands within the HIV-specific peptide repertoire presented by a protective HLA class I allotype, thereby enhancing our mechanistic understanding of the processes that enable NK cells to impact disease outcome. IMPORTANCE Natural killer (NK) cells are implicated as determinants of immune control in many viral infections, but the precise molecular mechanisms that initiate and control these responses are unclear. The activating receptor KIR3DS1 in combination with HLA-Bw4 has been associated with better outcomes in HIV infection. However, evidence of a direct interaction between these molecules is lacking. In this study, we demonstrate that KIR3DS1 recognition of HLA-Bw4 is peptide dependent. We also identify HIV-derived peptide epitopes presented by the protective HLA-B*57:01 allotype that facilitate productive interactions with KIR3DS1. Collectively, these findings suggest a mechanism whereby changes in the peptide repertoire associated with viral infection provide a trigger for KIR3DS1 engagement and NK cell activation. C1 [O'Connor, Geraldine M.; McVicar, Daniel W.] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA. [Vivian, Julian P.; Pymm, Phillip; Rossjohn, Jamie] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Clayton, Vic, Australia. [Vivian, Julian P.; Pymm, Phillip; Rossjohn, Jamie] Monash Univ, Australian Res Council Ctr Excellence Adv Mol Ima, Clayton, Vic, Australia. [Gostick, Emma; Price, David A.; Rossjohn, Jamie] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales. [Lafont, Bernard A. P.] NIAID, Nonhuman Primate Immunogenet & Cellular Immunol U, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Brooks, Andrew G.] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia. RP McVicar, DW (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA. EM mcvicard@mail.nih.gov RI Price, David/C-7876-2013; McVicar, Daniel/G-1970-2015; OI Price, David/0000-0001-9416-2737; Brooks, Andrew/0000-0002-4085-9683; Rossjohn, Jamie/0000-0002-2020-7522 FU Intramural AIDS Targeted Antiviral Program of the National Institutes of Health; National Health and Medical Research Council of Australia (NHMRC); Association for International Cancer Research; Intramural Research Program of the National Institutes of Health, National Cancer Institute and National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural AIDS Targeted Antiviral Program of the National Institutes of Health, the National Health and Medical Research Council of Australia (NHMRC), the Association for International Cancer Research (J.R. and A.G.B.), and the Intramural Research Program of the National Institutes of Health, National Cancer Institute and National Institute of Allergy and Infectious Diseases. J.P.V. is an Australian Research Council DECRA Fellow, D.A.P. is a Wellcome Trust Senior Investigator, and J.R. is an NHMRC Australia Fellow. NR 47 TC 18 Z9 18 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 2015 VL 89 IS 10 BP 5213 EP 5221 DI 10.1128/JVI.03586-14 PG 9 WC Virology SC Virology GA CG5KB UT WOS:000353329300004 PM 25740999 ER PT J AU Georgiev, IS Joyce, MG Yang, YP Sastry, M Zhang, BS Baxa, U Chen, RTE Druz, A Lees, CR Narpala, S Schon, A Van Galen, J Chuang, GY Gorman, J Harned, A Pancera, M Stewart-Jones, GBE Cheng, C Freire, E McDermott, AB Mascola, JR Kwong, PD AF Georgiev, Ivelin S. Joyce, M. Gordon Yang, Yongping Sastry, Mallika Zhang, Baoshan Baxa, Ulrich Chen, Rita E. Druz, Aliaksandr Lees, Christopher R. Narpala, Sandeep Schoen, Arne Van Galen, Joseph Chuang, Gwo-Yu Gorman, Jason Harned, Adam Pancera, Marie Stewart-Jones, Guillaume B. E. Cheng, Cheng Freire, Ernesto McDermott, Adrian B. Mascola, John R. Kwong, Peter D. TI Single-Chain Soluble BG505.SOSIP gp140 Trimers as Structural and Antigenic Mimics of Mature Closed HIV-1 Env SO JOURNAL OF VIROLOGY LA English DT Article ID BROADLY NEUTRALIZING ANTIBODIES; VIRUS ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODIES; VACCINE DEVELOPMENT; CONFORMATIONAL-CHANGES; GP41-GP120 INTERFACE; PRECURSOR CLEAVAGE; DEPENDENT EPITOPE; RECEPTOR-BINDING; TYPE-1 ENVELOPE AB Similar to other type I fusion machines, the HIV-1 envelope glycoprotein (Env) requires proteolytic activation; specifically, cleavage of a gp160 precursor into gp120 and gp41 subunits creates an N-terminal gp41 fusion peptide and permits folding from an immature uncleaved state to a mature closed state. While the atomic-level consequences of cleavage for HIV-1 Env are still being determined, the uncleaved state is antigenically distinct from the mature closed state, and cleavage has been reported to be essential for mimicry of the mature viral spike by soluble versions of Env. Here we report the redesign of a current state-of-the-art soluble Env mimic, BG505.SOSIP, to make it cleavage independent. Specifically, we replaced the furin cleavage site between gp120 and gp41 with Gly-Ser linkers of various lengths. The resultant linked gp120-gp41 constructs, termed single-chain gp140 (sc-gp140), exhibited different levels of structural and antigenic mimicry of the parent cleaved BG505.SOSIP. When constructs were subjected to negative selection to remove subspecies recognized by poorly neutralizing antibodies, trimers of high antigenic mimicry of BG505.SOSIP could be obtained; negative-stain electron microscopy indicated these to resemble the mature closed state. Higher proportions of BG505.SOSIP-trimer mimicry were observed in sc-gp140s with linkers of 6 or more residues, with a linker length of 15 residues exhibiting especially promising traits. Overall, flexible linkages between gp120 and gp41 in BG505.SOSIP can thus substitute for cleavage, and sc-gp140s that closely mimicked the vaccine-preferred mature closed state of Env could be obtained. IMPORTANCE The trimeric HIV-1 envelope glycoprotein (Env) is the sole target of virus-directed neutralizing antibody responses and a primary focus of vaccine design. Soluble mimics of Env have proven challenging to obtain and have been thought to require proteolytic cleavage into two-component subunits, gp120 and gp41, to achieve structural and antigenic mimicry of mature Env spikes on virions. Here we show that replacement of the cleavage site between gp120 and gp41 in a lead soluble gp140 construct, BG505.SOSIP, with flexible linkers can result in molecules that do not require cleavage to fold efficiently into the mature closed state. Our results provide insights into the impact of cleavage on HIV-1 Env folding. In some contexts such as genetic immunization, optimized cleavage-independent soluble gp140 constructs may have utility over the parental BG505.SOSIP, as they would not require furin cleavage to achieve mimicry of mature Env spikes on virions. C1 [Georgiev, Ivelin S.; Joyce, M. Gordon; Yang, Yongping; Sastry, Mallika; Zhang, Baoshan; Chen, Rita E.; Druz, Aliaksandr; Lees, Christopher R.; Narpala, Sandeep; Van Galen, Joseph; Chuang, Gwo-Yu; Gorman, Jason; Pancera, Marie; Stewart-Jones, Guillaume B. E.; Cheng, Cheng; McDermott, Adrian B.; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Baxa, Ulrich; Harned, Adam] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Electron Microscopy Lab, Canc Res Technol Program, Frederick, MD USA. [Schoen, Arne; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pdkwong@nih.gov FU Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases; Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E]; National Institutes of Health [GM056550]; National Science Foundation [MCB-1157506] FX Support for this study was provided by the following: the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases; federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E; and grants from the National Institutes of Health (GM056550 to E.F.) and from the National Science Foundation (MCB-1157506 to E.F.). NR 63 TC 24 Z9 25 U1 0 U2 17 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 2015 VL 89 IS 10 BP 5318 EP 5329 DI 10.1128/JVI.03451-14 PG 12 WC Virology SC Virology GA CG5KB UT WOS:000353329300013 PM 25740988 ER PT J AU Pesne, V Li, QS Sodroski, C Hsu, CS Liang, TJ AF Pesne, Veronique Li, Qisheng Sodroski, Catherine Hsu, Ching-Sheng Liang, T. Jake TI Dynamic Interaction of Stress Granules, DDX3X, and IKK-alpha Mediates Multiple Functions in Hepatitis C Virus Infection SO JOURNAL OF VIROLOGY LA English DT Article ID BOX RNA HELICASE; CORE PROTEIN; DEPENDENT TRANSLATION; PROCESSING BODIES; LIPID DROPLET; CELLULAR DDX3; REPLICATION; INNATE; GENOME; HCV AB The ubiquitous ATP-dependent RNA helicase DDX3X is involved in many cellular functions, including innate immunity, and is a pivotal host factor for hepatitis C virus (HCV) infection. Recently, we showed that DDX3X specifically recognizes the HCV 3' untranslated region (UTR), leading to the activation of IKK-alpha and a cascade of lipogenic signaling to facilitate lipid droplet biogenesis and viral assembly (Q. Li, V. Pene, S. Krishnamurthy, H. Cha, and T. J. Liang, Nat Med 19:722-729, 2013, http://dx.doi.org/10.1038/nm.3190). The interaction of DDX3X with HCV core protein seems to be dispensable for its proviral role. In this study, through systematic imaging and biochemical and virologic approaches, we identified a dynamic association between DDX3X and various cellular compartments and viral elements mediating multiple functions of DDX3X in productive HCV infection. Upon HCV infection, the HCV 3' UTR interacts with DDX3X and IKK-alpha, which redistribute to speckle-like cytoplasmic structures shown to be stress granules (SGs). As viral proteins accumulate in infected cells, DDX3X granules together with SG-associated proteins redistribute and colocalize with HCV core protein around lipid droplets (LDs). IKK-alpha, however, does not relocate to the LD but translocates to the nucleus. In HCV-infected cells, various HCV nonstructural proteins also interact or colocalize with DDX3X in close proximity to SGs and LDs, consistent with the tight juxtaposition of the replication complex and the assembly site at the surface of LDs. Short interfering RNA (siRNA)-mediated silencing of DDX3X and multiple SG components markedly inhibits HCV infection. Our data suggest that DDX3X initiates a multifaceted cellular program involving dynamic associations with HCV RNA and proteins, IKK-alpha, SG, and LD surfaces for its crucial role in the HCV life cycle. IMPORTANCE DDX3X is a proviral host factor for HCV infection. Recently, we showed that DDX3X binds to the HCV 3' UTR, activating IKK-alpha and cellular lipogenesis to facilitate viral assembly (Q. Li et al., Nat Med 19:722-729, 2013, http://dx.doi.org/10.1038/nm.3190). Here, we report associations of DDX3X with various cellular compartments and viral elements that mediate its multiple functions in the HCV life cycle. Upon infection, the HCV 3' UTR redistributes DDX3X and IKK-alpha to speckle-like cytoplasmic structures shown to be SGs. Subsequently, interactions between DDX3X, SG, and HCV proteins facilitate the translocation of DDX3X-SG complexes to the LD surface. HCV nonstructural proteins are shown to colocalize with DDX3X in close proximity to SGs and LDs, consistent with the tight juxtaposition of the HCV replication complex and assembly site at the LD surface. Our data demonstrate that DDX3X initiates a multifaceted cellular program involving dynamic associations with HCV elements, IKK-alpha, SGs, and LDs for its critical role in HCV infection. C1 [Pesne, Veronique; Li, Qisheng; Sodroski, Catherine; Hsu, Ching-Sheng; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Li, QS (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. EM liqisheng@niddk.nih.gov; jakel@bdg10.niddk.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), U.S. National Institutes of Health (NIH) FX This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), U.S. National Institutes of Health (NIH). NR 58 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 2015 VL 89 IS 10 BP 5462 EP 5477 DI 10.1128/JVI.03197-14 PG 16 WC Virology SC Virology GA CG5KB UT WOS:000353329300026 ER PT J AU Stenholm, S Shardell, M Bandinelli, S Guralnik, JM Ferrucci, L AF Stenholm, Sari Shardell, Michelle Bandinelli, Stefania Guralnik, Jack M. Ferrucci, Luigi TI Physiological Factors Contributing to Mobility Loss Over 9 Years of Follow-Up-Results From the InCHIANTI Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Physical functioning; Mobility loss; Physiological markers; Muscle strength; Central nervous system; Random survival forest ID PHYSICAL PERFORMANCE BATTERY; LOWER-EXTREMITY FUNCTION; MAINTAINING MOBILITY; RISK-FACTORS; FUNCTIONAL STATUS; OLDER-ADULTS; GAIT SPEED; LATE-LIFE; DISABILITY; DECLINE AB Background. Mobility is an essential aspect of everyday life and enables autonomy and participation. Although many risk factors for mobility loss have been previously described, their relative importance and independent contributions to the long-term risk of losing mobility have not been well defined. Methods. This study is based on 1,013 men and women aged >= 65 years enrolled in 1998-2000 and followed for 9 years through 2007-2008 in the population-based InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) study. We considered 44 different measures assessed at baseline to explore six subsystems: (i) central nervous system, (ii) peripheral nervous system, (iii) muscles, (iv) bone and joints, (v) energy production and delivery, and (vi) perceptual system. The outcome was incident mobility loss defined as self-report of inability to walk 400 m or climb and descend 10 steps without help from another person. Random survival forest analysis was used to rank the candidate predictors by their importance. Results. The most important physiological markers predicting mobility loss that emerged from the random survival forest modeling were older age among women (81-95 vs 65-68 years, hazard ratio [HR] 9.60 [95% CI 3.35, 27.50]), weaker ankle dorsiflexion strength (lowest vs highest quintile, HR 5.25 [95% CI 2.35, 11.72]), low hip flexion range of motion (lowest vs highest quintile, HR 2.30 [95% CI 1.20, 4.41]), presence of primitive reflexes (yes vs no, HR 1.47 [95% CI 1.03, 2.09]), and tremor (yes vs no, HR 1.91 [95% CI 1.18, 3.07]). Conclusion. Prevention of mobility loss with aging should focus on prevention and treatment of neuromuscular impairments. C1 [Stenholm, Sari] Univ Turku, Dept Publ Hlth, FI-20014 Turku, Finland. [Stenholm, Sari] Univ Tampere, Sch Hlth Sci, FIN-33101 Tampere, Finland. [Shardell, Michelle; Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. RP Stenholm, S (reprint author), Univ Turku, Dept Publ Hlth, FI-20014 Turku, Finland. EM sari.stenholm@utu.fi FU Academy of Finland [264944, 273850]; National Institute on Aging, National Institutes of Health, Baltimore, Maryland; Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002, 1 Z01 AG001050-01] FX This work was supported by grants from the Academy of Finland (264944 and 273850) and in part by the Intramural research program of the National Institute on Aging, National Institutes of Health, Baltimore, Maryland. The InCHIANTI study baseline (1998-2000) was supported as a "targeted project" (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (contracts: 263 MD 9164 and 263 MD 821336); the InCHIANTI Follow-up 1 (2001-2003) was funded by the U.S. National Institute on Aging (contracts: N.1-AG-1-1 and N.1-AG-1-2111); the InCHIANTI Follow-up 2 study (2004-2006) was financed by the U.S. National Institute on Aging (contract: N01-AG-5-0002); and the InCHIANTI Follow-up 3 study (2007-2008) was financed by the U.S. National Institute on Aging (contract: 1 Z01 AG001050-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 2 Z9 2 U1 4 U2 5 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 MAY PY 2015 VL 70 IS 5 BP 591 EP 597 DI 10.1093/gerona/glv004 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CH3AX UT WOS:000353899100006 PM 25748030 ER PT J AU Chen, DS Betz, J Yaffe, K Ayonayon, HN Kritchevsky, S Martin, KR Harris, TB Purchase-Helzner, E Satterfield, S Xue, QL Pratt, S Simonsick, EM Lin, FR AF Chen, David S. Betz, Joshua Yaffe, Kristine Ayonayon, Hilsa N. Kritchevsky, Stephen Martin, Kathryn R. Harris, Tamara B. Purchase-Helzner, Elizabeth Satterfield, Suzanne Xue, Qian-Li Pratt, Sheila Simonsick, Eleanor M. Lin, Frank R. CA Hlth ABC Study TI Association of Hearing Impairment with Declines in Physical Functioning and the Risk of Disability in Older Adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Physical function; Physical performance; Epidemiology ID LOWER-EXTREMITY FUNCTION; GAIT SPEED DECLINE; PERFORMANCE BATTERY; BODY-COMPOSITION; UNITED-STATES; SUBSEQUENT DISABILITY; VESTIBULAR FUNCTION; PROGNOSTIC VALUE; HEALTH; SURVIVAL AB Background: Identifying factors associated with functional declines in older adults is important given the aging of the population. We investigated if hearing impairment is independently associated with objectively measured declines in physical functioning in a community-based sample of older adults. Methods: Prospective observational study of 2,190 individuals from the Health, Aging, and Body Composition study. Participants were followed annually for up to 11 visits. Hearing was measured with pure-tone audiometry. Physical functioning and gait speed were measured with the Short Physical Performance Battery (SPPB). Incident disability and requirement for nursing care were assessed semiannually through self-report. Results: In a mixed-effects model, greater hearing impairment was associated with poorer physical functioning. At both Visit 1 and Visit 11, SPPB scores were lower in individuals with mild (10.14 [95% CI 10.04-10.25], p < .01; 7.35 [95% CI 7.12-7.58], p < .05) and moderate or greater hearing impairment (10.04 [95% CI 9.90-10.19], p < .01; 7.00 [95% CI 6.69-7.32], p < .01) than scores in normal hearing individuals (10.36 [95% CI 10.26-10.46]; 7.71 [95% CI 7.49-7.92]). We observed that women with moderate or greater hearing impairment had a 31% increased risk of incident disability (Hazard ratio [HR] = 1.31 [95% CI 1.08-1.60], p < .01) and a 31% increased risk of incident nursing care requirement (HR = 1.31 [95% CI 1.05-1.62], p = .02) compared to women with normal hearing. Conclusions: Hearing impairment is independently associated with poorer objective physical functioning in older adults, and a 31% increased risk for incident disability and need for nursing care in women. C1 [Chen, David S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Chen, David S.; Betz, Joshua; Xue, Qian-Li; Lin, Frank R.] Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA. [Yaffe, Kristine; Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kritchevsky, Stephen] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Martin, Kathryn R.; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Martin, Kathryn R.; Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Martin, Kathryn R.] Univ Aberdeen, Sch Med & Dent, Epidemiol Grp, Aberdeen, Scotland. [Purchase-Helzner, Elizabeth] Suny Downstate Med Ctr, Dept Epidemiol & Biostat, Brooklyn, NY 11203 USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Xue, Qian-Li] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Pratt, Sheila] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Pratt, Sheila] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Lin, Frank R.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. [Lin, Frank R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Lin, FR (reprint author), Johns Hopkins Ctr Aging & Hlth, 2024 Monument St,Suite 2-700, Baltimore, MD 21287 USA. EM flin1@jhmi.edu OI Betz, Joshua/0000-0003-4488-9799 FU NIH [K23DC011279]; Eleanor Schwartz Charitable Foundation; Triological Society/American College of Surgeons; National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01-AG028050]; NINR [R01NR012459]; NIH, National Institute on Aging FX This manuscript was supported in part by NIH K23DC011279, the Eleanor Schwartz Charitable Foundation, and a Triological Society/American College of Surgeons Clinician Scientist Award, as well as National Institute on Aging (NIA) Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant R01-AG028050, NINR grant R01NR012459, and the Intramural Research Program of the NIH, National Institute on Aging. NR 44 TC 14 Z9 15 U1 4 U2 15 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 MAY PY 2015 VL 70 IS 5 BP 654 EP 661 DI 10.1093/gerona/glu207 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CH3AX UT WOS:000353899100016 PM 25477427 ER PT J AU Brown, P Gipson, C AF Brown, Patricia Gipson, Chester TI A word from OLAW and USDA SO LAB ANIMAL LA English DT Editorial Material C1 [Brown, Patricia] HHS, NIH, OD, OER,OLAW, Washington, DC 20201 USA. [Gipson, Chester] USDA, APHIS, AC, Washington, DC USA. RP Brown, P (reprint author), HHS, NIH, OD, OER,OLAW, Washington, DC 20201 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 EI 1548-4475 J9 LAB ANIMAL JI Lab Anim. PD MAY PY 2015 VL 44 IS 5 BP 168 EP 168 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA CH2QK UT WOS:000353869500015 PM 25897933 ER PT J AU Cameron, D Higgins, DM Stehning, C Kouwenhoven, M Bouhrara, M Frenneaux, MP Dawson, DK Redpath, TW AF Cameron, Donnie Higgins, David M. Stehning, Christian Kouwenhoven, Marc Bouhrara, Mustapha Frenneaux, Michael P. Dawson, Dana K. Redpath, Thomas W. TI Selection of magnetization catalyzation and readout methods for modified Look-Locker inversion recovery: A T-1 mapping primer SO MAGNETIC RESONANCE IMAGING LA English DT Article DE T-1 mapping; Tissue characterization; Steady-state free precession; Transient signal oscillations ID MOLLI; RESONANCE; HEART; EXPERIENCE; SEQUENCE; SSFP AB Background: The purpose of this work was to evaluate different magnetization preparation and readout sequences for modified Look-Locker inversion recovery (MOLLI) toward improved T-1 mapping in the heart. Elements investigated include: catalyzation sequences to prepare the magnetization before readout, alternate k-space trajectories, a spoiled gradient recalled echo readout, and a 5b(3b)3b MOLLI sampling scheme ('b' denoting beats). Methods: Conventional 3b(3b)3b(3b)5b MOLLI with a linear k-space trajectory was compared to four variants in simulations, in vitro and in vivo (at 3T). Variants were centric conventional MOLLI, centric-paired conventional MOLLI, linear 5b(3b)3b MOLLI and spoiled gradient recalled echo MOLLI. Each of these was applied with three magnetization catalyzation methods, and T-1 measurement accuracy and precision were evaluated in simulations via a Monte Carlo algorithm, in a set of calibrated phantoms, and in ten healthy volunteers. Contrast-to-noise, heart rate dependence and B-1 + dependence were also evaluated. Results: A linear k-space trajectory was superior in vitro to centric and centric-paired trajectories. Of the catalyzation methods, preparation of transverse magnetization only using a linearly increasing flip angle catalyzation improved MOLLI T-1 measurement accuracy, precision, and map quality versus methods that include catalyzation of the longitudinal magnetization. The 5b(3b)3b MOLLI scheme offered comparable native T-1 measurement accuracy and precision to conventional MOLLI, despite its shortened acquisition. Conclusions: MOLLI T-1 measurement accuracy, precision, and map quality depend on the method of catalyzation of magnetization prior to image acquisition, as well as on the readout method and MOLLI sampling scheme used. (C) 2015 Elsevier Inc. All rights reserved. C1 [Cameron, Donnie; Frenneaux, Michael P.; Dawson, Dana K.; Redpath, Thomas W.] Univ Aberdeen, Aberdeen, Scotland. [Higgins, David M.] Philips Healthcare, Guildford, Surrey, England. [Stehning, Christian] Philips Res, Hamburg, Germany. [Kouwenhoven, Marc] Philips Healthcare, Best, Netherlands. [Bouhrara, Mustapha] NIA, NIH, Baltimore, MD 21224 USA. RP Cameron, D (reprint author), Harbor Hosp, NIA, 3001 Hanover St, Baltimore, MD 21225 USA. EM d.cameron.09@aberdeen.ac.uk; david.higgins@philips.com; christian.stehning@philips.com; marc.kouwenhoven@philips.com; mustapha.bouhrara2@nih.gov; m.p.frenneaux@abdn.ac.uk; dana.dawson@abdn.ac.uk; t.redpath@abdn.ac.uk NR 30 TC 1 Z9 1 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X EI 1873-5894 J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD MAY PY 2015 VL 33 IS 4 BP 363 EP 373 DI 10.1016/j.mri.2015.02.004 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CG9VW UT WOS:000353669200001 PM 25660643 ER PT J AU Ebong, IA Watson, KE Goff, DC Bluemke, DA Srikanthan, P Horwich, T Bertoni, AG AF Ebong, Imo A. Watson, Karol E. Goff, David C., Jr. Bluemke, David A. Srikanthan, Preethi Horwich, Tamara Bertoni, Alain G. TI Association of menopause age and N-terminal pro brain natriuretic peptide: the Multi-Ethnic Study of Atherosclerosis SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Menopause; N-Terminal pro brain natriuretic peptide; Sex hormones ID LEFT-VENTRICULAR HYPERTROPHY; INCIDENT HEART-FAILURE; CARDIOVASCULAR-DISEASE; NATURAL MENOPAUSE; RISK-FACTORS; MOLECULAR-MECHANISMS; POSTMENOPAUSAL WOMEN; METABOLIC SYNDROME; DIABETES-MELLITUS; MORTALITY AB Objective: Menopause age can affect the risk of developing cardiovascular disease (CVD). The purpose of this study was to investigate the associations of early menopause (menopause occurring before age 45 y) and menopause age with N-terminal pro brain natriuretic peptide (NT-proBNP), a potential risk marker of CVD and heart failure. Methods: Our cross-sectional study included 2,275 postmenopausal women, aged 45 to 85 years and without clinical CVD (2000-2002), fromthe Multi-Ethnic Study ofAtherosclerosis. Participants were classified as having or not having early menopause. NT-proBNP was log-transformed. Multivariable linear regression was used for analysis. Results: Five hundred sixty-one women had early menopause. The median (25th-75th percentiles) NT-proBNP value was 79.0 (41.1-151.6) pg/mL for all participants, 83.4 (41.4-164.9) pg/mL for women with early menopause, and 78.0 (40.8-148.3) pg/mL for women without early menopause. The mean (SD) age was 65 (10.1) and 65 (8.9) years for women with and without early menopause, respectively. No significant interactions between menopause age and ethnicity were observed. In multivariable analysis, early menopause was associated with a 10.7% increase in NT-proBNP levels, whereas each 1-year increase in menopause age was associated with a 0.7% decrease in NT-proBNP levels. Conclusions: Early menopause is associated with greater NT-proBNP levels, whereas each 1-year increase in menopause age is associated with lower NT-proBNP levels, in postmenopausal women. C1 [Ebong, Imo A.] Loma Linda Univ, Med Ctr, Inst Transplantat, Loma Linda, CA 92354 USA. [Watson, Karol E.; Horwich, Tamara] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, Los Angeles, CA 90095 USA. [Goff, David C., Jr.] Colorado Sch Publ Hlth, Aurora, CO USA. [Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Srikanthan, Preethi] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Bertoni, Alain G.] Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Winston Salem, NC 27103 USA. [Bertoni, Alain G.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol, Winston Salem, NC USA. RP Ebong, IA (reprint author), Loma Linda Univ, Med Ctr, Inst Transplantat, Suite 101,25865 Barton Rd, Loma Linda, CA 92354 USA. EM momoebong4@gmail.com OI Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169] FX The Multi-Ethnic Study of Atherosclerosis was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute. NR 57 TC 1 Z9 1 U1 1 U2 2 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 MAY PY 2015 VL 22 IS 5 BP 527 EP 533 DI 10.1097/gme.0000000000000342 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CG9ZB UT WOS:000353677500009 PM 25290536 ER PT J AU Lasota, J Felisiak-Golabek, A Aly, FZ Wang, ZF Thompson, LDR Miettinen, M AF Lasota, Jerzy Felisiak-Golabek, Anna Aly, F. Zahra Wang, Zeng-Feng Thompson, Lester D. R. Miettinen, Markku TI Nuclear expression and gain-of-function beta-catenin mutation in glomangiopericytoma (sinonasal-type hemangiopericytoma): insight into pathogenesis and a diagnostic marker SO MODERN PATHOLOGY LA English DT Article ID SOLITARY FIBROUS TUMORS; CYCLIN D1; DIFFERENTIAL-DIAGNOSIS; MYOID DIFFERENTIATION; CARCINOMA-CELLS; GLOMUS TUMORS; ACTIVATION; CANCER; GENE; IMMUNOHISTOCHEMISTRY AB Glomangiopericytoma (sinonasal-type hemangiopericytoma) is a rare mesenchymal neoplasm with myoid phenotype (smooth muscle actin-positive), which distinguishes this tumor from soft tissue hemangiopericytoma/solitary fibrous tumor. Molecular genetic changes underlying the pathogenesis of glomangiopericytoma are not known. In this study, 13 well-characterized glomangiopericytomas were immunohistochemically evaluated for beta-catenin expression. All analyzed tumors showed strong expression and nuclear accumulation of beta-catenin. Following this observation, beta-catenin glycogen serine kinase-3 beta phosphorylation region, encoded by exon 3, was PCR amplified in all cases and evaluated for mutations using Sanger sequencing. Heterozygous mutations were identified in 12 of 13 tumors. All mutations consisted of single-nucleotide substitutions: three in codon 32 (c.94G4C (n = 2) and c.95A4T), four in codon 33 (two each c.98C4G and c.98C4T), two in codon 37 (c.109T4G), one in codon 41 (c.121A4G), and two in codon 45 (c.133T4C). At the protein level, these substitutions would lead to p.D32H, p.D32V, p.S33C, p.S33F, p.S37A, p.T41A, and p.S45L mutations, respectively. Previously, similar mutations have been reported in different types of cancers and shown to trigger activation of beta-catenin signaling. All analyzed glomangiopericytomas showed prominent nuclear expression of cyclin D1, as previously shown for tumors with nuclear expression of beta-catenin as a sign of oncogenic activation. These results demonstrate that mutational activation of b beta-catenin and associated cyclin D1 overexpression may be central events in the pathogenesis of glomangiopericytoma. In additon, nuclear accumulation of beta-catenin is a diagnostic marker for glomangiopericytoma. C1 [Lasota, Jerzy; Felisiak-Golabek, Anna; Wang, Zeng-Feng; Miettinen, Markku] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Aly, F. Zahra] Univ Arizona, Dept Pathol, Tucson, AZ USA. [Thompson, Lester D. R.] So Calif Permanente Med Grp, Dept Pathol, Woodland Hills, CA USA. RP Lasota, J (reprint author), NCI, Pathol Lab, 9000 Rockville Pike,Bldg 10,Room B1B47, Bethesda, MD 20892 USA. EM jerzy.lasota@nih.gov RI Thompson, Lester/J-8404-2016 OI Thompson, Lester/0000-0003-3714-1432 NR 28 TC 8 Z9 9 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 2015 VL 28 IS 5 BP 715 EP 720 DI 10.1038/modpathol.2014.161 PG 6 WC Pathology SC Pathology GA CH1IE UT WOS:000353774200011 PM 25431235 ER PT J AU Stalnaker, TA Cooch, NK Schoenbaum, G AF Stalnaker, Thomas A. Cooch, Nisha K. Schoenbaum, Geoffrey TI What the orbitofrontal cortex does not do SO NATURE NEUROSCIENCE LA English DT Review ID VENTROMEDIAL PREFRONTAL CORTEX; DOPAMINE NEURONS ENCODE; FRONTAL-LOBE DAMAGE; VENTRAL TEGMENTAL AREA; DECISION-MAKING; BASOLATERAL AMYGDALA; REWARD VALUE; REINFORCER DEVALUATION; RHESUS-MONKEYS; ECONOMIC VALUE AB The number of papers about the orbitofrontal cortex (OFC) has grown from 1 per month in 1987 to a current rate of over 50 per month. This publication stream has implicated the OFC in nearly every function known to cognitive neuroscience and in most neuropsychiatric diseases. However, new ideas about OFC function are typically based on limited data sets and often ignore or minimize competing ideas or contradictory findings. Yet true progress in our understanding of an area's function comes as much from invalidating existing ideas as proposing new ones. Here we consider the proposed roles for OFC, critically examining the level of support for these claims and highlighting the data that call them into question. C1 [Stalnaker, Thomas A.; Cooch, Nisha K.; Schoenbaum, Geoffrey] US Natl Inst Hlth, Natl Inst Drug Abuse Intramural Res Program, Baltimore, MD 21224 USA. RP Schoenbaum, G (reprint author), US Natl Inst Hlth, Natl Inst Drug Abuse Intramural Res Program, Baltimore, MD 21224 USA. EM geoffrey.schoenbaum@nih.gov OI Schoenbaum, Geoffrey/0000-0001-8180-0701 FU National Institute on Drug Abuse; National Institute of Mental Health; National Institute on Aging; National Institute on Drug Abuse at the Intramural Research Program FX The authors would like to thank C. Padoa-Schioppa, J. Wallis and P. Rudebeck for critical readings of earlier versions. This work was supported by grants to G.S. from the National Institute on Drug Abuse, the National Institute of Mental Health and the National Institute on Aging while G.S. was employed at the University of Maryland, Baltimore, and by funding from the National Institute on Drug Abuse at the Intramural Research Program. The opinions expressed in this article are the authors' own and do not reflect the view of the US National Institutes of Health, the Department of Health and Human Services, or the United States government. NR 150 TC 55 Z9 57 U1 12 U2 57 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2015 VL 18 IS 5 BP 620 EP 627 DI 10.1038/nn.3982 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CG9LN UT WOS:000353636900007 PM 25919962 ER PT J AU Wang, DV Yau, HJ Broker, CJ Tsou, JH Bonci, A Ikemoto, S AF Wang, Dong V. Yau, Hau-Jie Broker, Carl J. Tsou, Jen-Hui Bonci, Antonello Ikemoto, Satoshi TI Mesopontine median raphe regulates hippocampal ripple oscillation and memory consolidation SO NATURE NEUROSCIENCE LA English DT Article ID URETHANE-ANESTHETIZED RAT; THETA-RHYTHM; PREFRONTAL CORTEX; SPATIAL MEMORY; SEROTONERGIC CONTROL; NUCLEUS; NEURONS; BRAIN; DORSAL; SLEEP AB Sharp wave-associated field oscillations (similar to 200 Hz) of the hippocampus, referred to as ripples, are believed to be important for consolidation of explicit memory. Little is known about how ripples are regulated by other brain regions. We found that the median raphe region (MnR) is important for regulating hippocampal ripple activity and memory consolidation. We performed in vivo simultaneous recording in the MnR and hippocampus of mice and found that, when a group of MnR neurons was active, ripples were absent. Consistently, optogenetic stimulation of MnR neurons suppressed ripple activity and inhibition of these neurons increased ripple activity. Notably, using a fear conditioning procedure, we found that photostimulation of MnR neurons interfered with memory consolidation. Our results demonstrate a critical role of the MnR in regulating ripples and memory consolidation. C1 [Wang, Dong V.; Yau, Hau-Jie; Broker, Carl J.; Tsou, Jen-Hui; Bonci, Antonello; Ikemoto, Satoshi] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Ikemoto, S (reprint author), NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM satoshi.ikemoto@nih.gov OI YAU, HAU-JIE/0000-0001-7454-7971; Ikemoto, Satoshi/0000-0002-0732-7386 FU Intramural Research Program of NIDA; Ministry of Science and Technology, Taiwan [MOST 103-2911-I-038-501] FX We thank the National Institute on Drug Abuse (NIDA) Optogenetics and Transgenetic Technology Core for producing AAVs, E. Deneris (Case Western Reserve University) for providing the ePet-Cre mouse line, R. Cachope, J. Cheer, C. Mejias-Aponte, M. Moralas, A. Kesner, A. Ilango, C. Yang, D. Nguyen and M. Vatsan for technical assistance, and S.-C. Lin, Y. Shaham, G. Schoenbaum and A. Saul for reading and critical discussions. This research was supported by the Intramural Research Program of NIDA and the grant MOST 103-2911-I-038-501 from the Ministry of Science and Technology, Taiwan. NR 51 TC 11 Z9 11 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2015 VL 18 IS 5 BP 728 EP + DI 10.1038/nn.3998 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CG9LN UT WOS:000353636900020 PM 25867120 ER PT J AU Wang, Z Wang, F Hida, N Kiesewetter, DO Tian, J Niu, G Chen, XY AF Wang, Zhe Wang, Fu Hida, Naoki Kiesewetter, Dale O. Tian, Jie Niu, Gang Chen, Xiaoyuan TI Design of a functional cyclic HSV1-TK reporter and its application to PET imaging of apoptosis SO NATURE PROTOCOLS LA English DT Article ID SIMPLEX-VIRUS TYPE-1; POSITRON-EMISSION-TOMOGRAPHY; THYMIDINE KINASE; CELL-DEATH; GENE-EXPRESSION; REAL-TIME; TRANSGENIC MICE; CANCER-CELLS; ANNEXIN-V; IN-VITRO AB Positron emission tomography (PET) is a sensitive and noninvasive imaging method that is widely used to explore molecular events in living subjects. PET can precisely and quantitatively evaluate cellular apoptosis, which has a crucial role in various physiological and pathological processes. In this protocol, we describe the design and use of an engineered cyclic herpes simplex virus 1-thymidine kinase (HSV1-TK) PET reporter whose kinase activity is specifically switched on by apoptosis. The expression of cyclic TK (cTK) in healthy cells leads to inactive product, whereas the activation of apoptosis through the caspase-3 pathway cleaves cTK, thus restoring its activity and enabling PET imaging. In addition to detailing the design and construction of the cTK plasmid in this protocol, we include assays for evaluating the function and specificity of the cTK reporter in apoptotic cells, such as assays for measuring the cell uptake of PET tracer in apoptotic cells, correlating doxorubicin (Dox)-induced cell apoptosis to cTK function recovery, and in vivo PET imaging of cancer cell apoptosis, and we also include corresponding data acquisition methods. The time to build the entire cTK reporter is similar to 2-3 weeks. The selection of a stable cancer cell line takes similar to 4-6 weeks. The time to implement assays regarding cTK function in apoptotic cells and the in vivo imaging varies depending on the experiment. The cyclization strategy described in this protocol can also be adapted to create other reporter systems for broad biomedical applications. C1 [Wang, Zhe; Hida, Naoki; Kiesewetter, Dale O.; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA. [Wang, Fu; Tian, Jie] Xidian Univ, Sch Life Sci & Technol, Xian, Peoples R China. RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA. EM gang.niu@nih.gov; shawn.chen@nih.gov RI Song, Jiangdian/L-6992-2016; Tian, Jie/H-1190-2011; OI Song, Jiangdian/0000-0002-3355-9930; Tian, Jie/0000-0003-0498-0432; Wang, Fu/0000-0001-9222-0833 FU Center for Neuroscience and Regeneration Medicine Program at the Henry M. Jackson Foundation; National Institute of Biomedical Imaging and Bioengineering, US National Institutes of Health (NIH) FX This work was supported, in part, by the Center for Neuroscience and Regeneration Medicine Program at the Henry M. Jackson Foundation, and by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, US National Institutes of Health (NIH). We thank T. Ozawa (University of Tokyo) for providing us with the cDNAs of DnaE and PEST. NR 50 TC 1 Z9 1 U1 4 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD MAY PY 2015 VL 10 IS 5 BP 807 EP 821 DI 10.1038/nprot.2015.048 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CH1KJ UT WOS:000353780000011 PM 25927390 ER PT J AU Mailankody, S Korde, N Lesokhin, AM Lendvai, N Hassoun, H Stetler-Stevenson, M Landgren, O AF Mailankody, Sham Korde, Neha Lesokhin, Alexander M. Lendvai, Nikoletta Hassoun, Hani Stetler-Stevenson, Maryalice Landgren, Ola TI Minimal residual disease in multiple myeloma: bringing the bench to the bedside SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID STEM-CELL TRANSPLANTATION; MULTIPARAMETER FLOW-CYTOMETRY; COMPLETE RESPONSE; PERIPHERAL-BLOOD; BONE-MARROW; CANCER; PCR; HETEROGENEITY; DEXAMETHASONE; LENALIDOMIDE AB Outcomes for patients with multiple myeloma (MM) have improved substantially in the past decade, with improvements in both progression-free survival and overall survival. Many patients are now achieving a complete response to treatment, and consequently highly sensitive assays are needed for detection of minimal residual disease (MRD) in patients with MM. Results of multicolour flow cytometry and deep-sequencing studies suggest that among patients achieving a complete response, MRD-negative status is associated with significant improvements in progression-free survival and overall survival. Despite the increasing need for MRD testing in patients with MM, considerable heterogeneity in techniques for MRD detection hinders the clinical interpretation of their results. The criteria used to define MRD, strengths and weaknesses of the major types of tests (flow cytometry versus molecular testing), and the optimal sample type (bone marrow aspirate versus peripheral blood) are all unresolved dilemmas in MRD testing. This Review presents an overview of the various techniques for MRD detection in patients with MM. In addition, this article discusses challenges and opportunities for the routine use of MRD testing, possible future directions for clinical trials and implications for drug approval processes. C1 [Mailankody, Sham] NCI, Multiple Myeloma Sect, Lymphoid Malignancies Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Stetler-Stevenson, Maryalice] NCI, Flow Cytometry Lab, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Korde, Neha; Lesokhin, Alexander M.; Lendvai, Nikoletta; Hassoun, Hani; Landgren, Ola] Mem Sloan Kettering Canc Ctr, Myeloma Serv, New York, NY 10065 USA. RP Landgren, O (reprint author), Mem Sloan Kettering Canc Ctr, Myeloma Serv, 1275 York Ave, New York, NY 10065 USA. EM landgrec@mskcc.org FU National Cancer Institute, Bethesda, MD, USA FX S.M. and M.S.-S. gratefully acknowledge support from the Intramural Research Program of the National Cancer Institute, Bethesda, MD, USA. NR 43 TC 22 Z9 23 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD MAY PY 2015 VL 12 IS 5 BP 286 EP U139 DI 10.1038/nrclinonc.2014.239 PG 10 WC Oncology SC Oncology GA CH1LP UT WOS:000353783400007 PM 25622976 ER PT J AU Tsai, MS Lee, ML Chang, CY Fan, HH Yu, IS Chen, YT You, JY Chen, CY Chang, FC Hsiao, JH Khorkova, O Liou, HH Yanagawa, Y Lee, LJ Lin, SW AF Tsai, Ming-Shian Lee, Meng-Larn Chang, Chun-Yun Fan, Hsiang-Hsuan Yu, I-Shing Chen, You-Tzung You, Jhih-Yi Chen, Chun-Yu Chang, Fang-Chia Hsiao, Jane H. Khorkova, Olga Liou, Horng-Huei Yanagawa, Yuchio Lee, Li-Jen Lin, Shu-Wha TI Functional and structural deficits of the dentate gyrus network coincide with emerging spontaneous seizures in an Scn1a mutant Dravet Syndrome model during development SO NEUROBIOLOGY OF DISEASE LA English DT Article DE SCN1A; Dravet syndrome; Epilepsy; Mouse model ID GABAERGIC SYNAPTIC-TRANSMISSION; HYPERTHERMIA-INDUCED SEIZURES; EXPERIMENTAL FEBRILE SEIZURES; SEVERE MYOCLONIC EPILEPSY; MOUSE MODEL; PYRAMIDAL NEURONS; RAT HIPPOCAMPUS; INHIBITORY INTERNEURONS; ELECTRICAL-STIMULATION; CORTICAL INTERNEURONS AB Dravet syndrome (DS) is characterized by severe infant-onset myoclonic epilepsy along with delayed psychomotor development and heightened premature mortality. A primary monogenic cause is mutation of the SCN1A gene, which encodes the voltage-gated sodium channel subunit Na(v)1:1. The nature and timing of changes caused by SCN1A mutation in the hippocampal dentate gyrus (DG) network, a core area for gating major excitatory input to hippocampus and a classic epileptogenic zone, are not well known. In particularly, it is still not clear whether the developmental deficit of this epileptogenic neural network temporally matches with the progress of seizure development. Here, we investigated the emerging functional and structural deficits of the DG network in a novel mouse model (scn1a(E1099X/+)) that mimics the genetic deficit of human DS. Scn1a(E1099X/+) (Het) mice, similarly to human DS patients, exhibited early spontaneous seizures and were more susceptible to hyperthermia-induced seizures starting at postnatal week (PW) 3, with seizures peaking at PW4. During the same period, the Het DG exhibited a greater reduction of Na(v)1.1-expressing GABAergic neurons compared to other hippocampal areas. Het DG GABAergic neurons showed altered action potential kinetics, reduced excitability, and generated fewer spontaneous inhibitory inputs into DG granule cells. The effect of reduced inhibitory input to DC granule cells was exacerbated by heightened spontaneous excitatory transmission and elevated excitatory release probability in these cells. In addition to electrophysiological deficit, we observed emerging morphological abnormalities of DG granule cells. Het granule cells exhibited progressively reduced dendritic arborization and excessive spines, which coincided with imbalanced network activity and the developmental onset of spontaneous seizures. Taken together, our results establish the existence of significant structural and functional developmental deficits of the DG network and the temporal correlation between emergence of these deficits and the onset of seizures in Net animals. Most importantly, our results uncover the developmental deficits of neural connectivity in Net mice. Such structural abnormalities likely further exacerbate network instability and compromise higher-order cognitive processing later in development, and thus highlight the multifaceted impacts of Scn1a deficiency on neural development. (C) 2015 Elsevier Inc. All rights reserved. C1 [Tsai, Ming-Shian; You, Jhih-Yi; Chen, Chun-Yu; Lin, Shu-Wha] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Dept Clin Lab Sci & Med Biotechnol, Taipei 100, Taiwan. [Lee, Meng-Larn; Chang, Fang-Chia] Natl Taiwan Univ, Dept Vet Med, Taipei 100, Taiwan. [Chang, Chun-Yun] NIDA, Intramural Res Program, Baltimore, MD 21224 USA. [Fan, Hsiang-Hsuan; Chen, You-Tzung] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Grad Inst Med Genom & Prote, Taipei 100, Taiwan. [Yu, I-Shing] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Lab Anim Ctr, Taipei 100, Taiwan. [Hsiao, Jane H.; Khorkova, Olga] OPKO Hlth Inc, Miami, FL 33137 USA. [Liou, Horng-Huei] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Dept Neurol, Taipei 100, Taiwan. [Yanagawa, Yuchio] Gunma Univ, Grad Sch Med, Dept Genet & Behav Neurosci, Maebashi, Gumma 3718511, Japan. [Yanagawa, Yuchio] JST, CREST, Maebashi, Gumma 3718511, Japan. [Lee, Li-Jen] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Grad Inst Anat & Cell Biol, Taipei 100, Taiwan. [Lee, Li-Jen] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Grad Inst Brain & Mind Sci, Taipei 100, Taiwan. [Lin, Shu-Wha] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Dept Lab Med, Taipei 100, Taiwan. [Lin, Shu-Wha] Natl Taiwan Univ, Ctr Genom Med, Taipei 100, Taiwan. RP Lee, LJ (reprint author), Natl Taiwan Univ, Coll Med, Grad Inst Anat & Cell Biol, 1 Sect 1,Ren Ai Rd, Taipei 100, Taiwan. EM ljlee@ntu.edu.tw; mtshuwha@ntu.edu.tw OI LEE, LI-JEN/0000-0001-9108-3654; CHEN, YOU-TZUNG/0000-0001-6510-3420; LIN, SHU-WHA/0000-0001-6748-5581 FU National Taiwan University [103R7152]; Ministry of Science and Technology [MOST 103-2321-B-002-018]; Ministry of Health and Welfare in Taiwan [MOHW103-TDU-PB-211-133008]; MEXT of Japan; Takeda Science Foundation FX Funding for this study was provided by National Taiwan University (103R7152), the Ministry of Science and Technology (MOST 103-2321-B-002-018), and the Ministry of Health and Welfare in Taiwan (MOHW103-TDU-PB-211-133008) for SW Lin, and the MEXT of Japan and Takeda Science Foundation for Y Yanagawa. NR 66 TC 4 Z9 5 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD MAY PY 2015 VL 77 BP 35 EP 48 DI 10.1016/j.nbd.2015.02.010 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CG9CO UT WOS:000353612200004 PM 25725421 ER PT J AU Messer, K White, MM Strong, DR Wang, B Shi, Y Conway, KP Pierce, JP AF Messer, Karen White, Martha M. Strong, David R. Wang, Baoguang Shi, Yuyan Conway, Kevin P. Pierce, John P. TI Trends in Use of Little Cigars or Cigarillos and Cigarettes among U.S. Smokers, 2002-2011 SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID TOBACCO PRODUCTS; UNITED-STATES; ADOLESCENTS; PREVALENCE; CALIFORNIA; PATTERNS; EXPLAINS; SMOKING AB Objectives: Little cigars and cigarillos may resemble cigarettes, but may be less expensive and can be purchased singly and in flavored varieties. We used two major U.S. surveys to investigate use of cigarillos and cigarettes. Methods: The 2010/2011 Tobacco Use Supplement to the Current Population Survey ascertained cigar use by brand and type (little cigars/cigarillos or large/regular). The annual National Survey on Drug Use and Health (NSDUH) assessed cigar use by brand, 2002-2011. We used the available data to classify cigars by type among males in the NSDUH. Results: Estimated prevalence of little cigar use among male cigar smokers was similar using the two surveys. From 2002 to 2011, past-30-day cigarette smoking declined for all age groups and genders, but among young adult men (aged 18-25) little cigar smoking remained steady at nearly 9%. "Cigarette and/or cigar" smoking was 44% among young adult men in 2011, and was consistently 6 percentage points higher than cigarette-only smoking, from 2002 to 2011. Over 60% of male and 70% of female adolescent/young adult cigar smokers also smoked cigarettes in 2011. Most male adolescents preferred little cigars to traditional cigars. Among males, most lower income or less educated cigar smokers preferred little cigars, compared to only 16% of those with higher education. Conclusions: These patterns indicate that little cigar/cigarillo use may promote initiation and maintenance of cigarette smoking, particularly among younger and less advantaged populations. Population-level data are urgently needed to better assess type of cigar smoked and reasons for use. C1 [Messer, Karen; White, Martha M.; Strong, David R.; Shi, Yuyan; Pierce, John P.] Univ Calif San Diego, Canc Prevent & Control Div, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA. [Wang, Baoguang] US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA. [Conway, Kevin P.] Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, Rockville, MD USA. RP Messer, K (reprint author), Univ Calif San Diego, Div Biostat, Dept Family & Prevent Med, 3855 Hlth Sci Dr,0901, La Jolla, CA 92093 USA. EM kmesser@ucsd.edu OI Conway, Kevin/0000-0002-7638-339X FU National Institute on Drug Abuse, National Institutes of Health; Food and Drug Administration; Department of Health and Human Services [HHSN271201100027C]; UC Tobacco-Related Disease Research Program [21RT-0135, 21XT-0076]; National Cancer Institute [1R01CA172058-01] FX This project has been funded in whole or in part with Federal funds from the National Institute on Drug Abuse, National Institutes of Health, and the Food and Drug Administration, Department of Health and Human Services, under Contract No. HHSN271201100027C, UC Tobacco-Related Disease Research Program grants 21RT-0135 and 21XT-0076, and National Cancer Institute grant No. 1R01CA172058-01. The views and opinions expressed in this presentation are those of the authors only and do not necessarily represent the views, official policy or position of the U.S. Department of Health and Human Services or any of its affiliated institutions or agencies. NR 26 TC 5 Z9 5 U1 3 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD MAY PY 2015 VL 17 IS 5 BP 515 EP 523 DI 10.1093/ntr/ntu179 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA CH3CL UT WOS:000353904000003 PM 25239955 ER PT J AU Ekenga, CC Parks, CG Wilson, LE Sandler, DP AF Ekenga, Christine C. Parks, Christine G. Wilson, Lauren E. Sandler, Dale P. TI Leisure-time physical activity in relation to occupational physical activity among women SO PREVENTIVE MEDICINE LA English DT Article DE Physical activity; Workplace; Women AB Objective. The objective of this study is to examine the association between occupational physical activity and leisure-time physical activity among US women in the Sister Study. Methods. We conducted a cross-sectional study of 26,334 women who had been employed in their current job for at least 1 year at baseline (2004-2009). Occupational physical activity was self-reported and leisure-time physical activity was estimated in metabolic equivalent hours per week. Log multinomial regression was used to evaluate associations between occupational (sitting, standing, manually active) and leisure-time (insufficient, moderate, high) activity. Models were adjusted for age, race/ethnicity, education, income, geographic region, and body mass index. Results. Only 54% of women met or exceeded minimum recommended levels of leisure-time physical activity (moderate 32% and high 22%). Women who reported sitting (prevalence ratio (PR) = 0.82, 95% confidence interval (CI): 0.74-0.92) or standing (PR = 0.84, 95% CI: 0.75-0.94) most of the time at work were less likely to meet the requirements for high leisure-time physical activity than manually active workers. Associations were strongest among women living in the Northeast and the South. Conclusion. In this nationwide study, low occupational activity was associated with lower leisure-time physical activity. Women who are not active in the workplace may benefit from strategies to promote leisure-time physical activity. Published by Elsevier Inc. C1 [Ekenga, Christine C.; Parks, Christine G.; Wilson, Lauren E.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Ekenga, CC (reprint author), NIEHS, Epidemiol Branch, POB 12233,Mail Drop A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM christine.ekenga@nih.gov OI Parks, Christine/0000-0002-5734-3456; Sandler, Dale/0000-0002-6776-0018; Wilson, Lauren/0000-0002-5953-2293 FU Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences [Z01ES044005] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01ES044005). The authors would like to thank Drs. Katie O'Brien and Quaker Harmon for their helpful comments. NR 11 TC 0 Z9 0 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD MAY PY 2015 VL 74 BP 93 EP 96 DI 10.1016/j.ypmed.2015.03.003 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA CH1AX UT WOS:000353754600015 PM 25773471 ER PT J AU Djousse, L Petrone, AB Blackshear, C Griswold, M Harman, JL Clark, CR Talegawkar, S Hickson, DA Gaziano, JM Dubbert, PM Correa, A Tucker, KL Taylor, HA AF Djousse, Luc Petrone, Andrew B. Blackshear, Chad Griswold, Michael Harman, Jane L. Clark, Cheryl R. Talegawkar, Sameera Hickson, DeMarc A. Gaziano, J. Michael Dubbert, Patricia M. Correa, Adolfo Tucker, Katherine L. Taylor, Herman A. TI Prevalence and changes over time of ideal cardiovascular health metrics among African-Americans: The Jackson Heart Study SO PREVENTIVE MEDICINE LA English DT Article DE Epidemiology; Cardiovascular disease; Risk factors; Diet ID ATHEROSCLEROSIS RISK; PHYSICAL-ACTIVITY; DISEASE INCIDENCE; US ADULTS; ASSOCIATION; MORTALITY; COMMUNITIES; WOMEN; POPULATION; UPDATE AB Objectives. The aim of this study is to assess the prevalence and changes over time of ideal Life's Simple Seven (LSS) in African-Americans. Methods. Prospective cohort of 5301 African-Americans from the Jackson Heart Study OHS) from 2000 to 2013. Each of the LSS metrics was categorized as poor, intermediate, or ideal. Results. Among men, the prevalence of having 0, 1, 2, 3, 4, 5, 6, and 7 ideal LSS was 3.3%, 23.0%, 33.5%, 24.7%, 11.6%, 3.6%, 0.3%, and 0%, respectively. Corresponding values for women were 1.7%, 26.3%, 33.1%, 22.8%, 11.9%, 3.7%, 0.6%, and 0%. Prevalence of ideal diet was 0.9%. The proportions of those meeting LSS ideal recommendations for cholesterol and fasting glucose declined from the first through third JHS visits across all age groups, whereas prevalence of ideal BMI declined only in participants <40 years at a given visit. Prevalence of ideal blood pressure did not change over time and being ideal on physical activity improved from the first [18.3% (95% CI: 17.3% to 19.3%)] to third visit [24.8% (95% CI: 23.3% to 26.3%)]. Conclusions. Our data show a low prevalence of ideal LSS (especially diet, physical activity, and obesity) in the JHS and a slight improvement in adherence to physical activity recommendations over time. (C) 2015 Elsevier Inc. All rights reserved. C1 [Djousse, Luc; Petrone, Andrew B.; Clark, Cheryl R.; Gaziano, J. Michael] Brigham & Womens Hosp, Boston, MA 02120 USA. [Djousse, Luc; Gaziano, J. Michael] Boston VA Healthcare Syst, Boston, MA USA. [Djousse, Luc; Clark, Cheryl R.; Gaziano, J. Michael] Harvard Univ, Sch Med, Boston, MA USA. [Blackshear, Chad; Griswold, Michael; Hickson, DeMarc A.; Correa, Adolfo; Taylor, Herman A.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Harman, Jane L.] NHLBI, Bethesda, MD 20892 USA. [Talegawkar, Sameera] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Dubbert, Patricia M.] South Cent VA MIRECC, Little Rock, AR USA. [Dubbert, Patricia M.] Little Rock GRECC, Little Rock, AR USA. [Tucker, Katherine L.] Univ Massachusetts Lowell, Lowell, MA USA. [Taylor, Herman A.] Jackson State Univ, Jackson, MS USA. [Taylor, Herman A.] Tougaloo Coll, Jackson, MS USA. RP Djousse, L (reprint author), Brigham & Womens Hosp, Div Aging, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM ldjousse@rics.bwh.harvard.edu RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]; National Institute on Minority Health and Health Disparities; National Health Institutes [R21 NR013231]; American Diabetes Association [13BGIA17080036] FX The Jackson Heart Study is supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, and HHSN268201300050C from the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities. This project was also supported by grant R21 NR013231 from the National Health Institutes. Dr. Talegawkar was supported by grant 13BGIA17080036 from the American Diabetes Association. NR 35 TC 6 Z9 6 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD MAY PY 2015 VL 74 BP 111 EP 116 DI 10.1016/j.ypmed.2015.02.006 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA CH1AX UT WOS:000353754600018 PM 25712326 ER PT J AU Blanchard, HC Taha, AY Rapoport, SI Yuan, ZX AF Blanchard, Helene C. Taha, Ameer Y. Rapoport, Stanley I. Yuan, Zhi-Xin TI Low-dose aspirin (acetylsalicylate) prevents increases in brain PGE(2), 15-epi-lipoxin A4 and 8-isoprostane concentrations in 9 month-old HIV-1 transgenic rats, a model for HIV-1 associated neurocognitive disorders SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Review DE HIV-1; PGE(2); 8-Isoprostane; Brain; Chronic aspirin; Rat ID OXIDATIVE STRESS; INFECTED PATIENTS; ANTIRETROVIRAL THERAPY; ALZHEIMERS-DISEASE; ANTI-INFLAMMATION; ASTROCYTOMA-CELLS; ACID; CYCLOOXYGENASE-2; ACTIVATION; MARKERS AB Background: Older human immunodeficiency virus (HIV)-1 transgenic rats are a model for HIV-1 associated neurocognitive disorders (HAND). They show behavioral changes, neuroinflammation, neuronal loss, and increased brain arachidonic acid (AA) enzymes. Aspirin (acetylsalicylate, ASA) inhibits AA oxidation by cyclooxygenase (COX)-1 and COX-2. Hypothesis: Chronic low-dose ASA will downregulate brain AA metabolism in HIV-1 transgenic rats. Methods: Nine month-old HIV-1 transgenic and wildtype rats were given 42 days of 10 mg/kg/day ASA or nothing in drinking water; eicosanoids were measured using ELISAs on microwaved brain extracts. Results: Brain 15-epi-lipoxin A4 and 8-isoprostane concentrations were significantly higher in HIV-1 transgenic than wildtype rats; these differences were prevented by ASA. ASA reduced prostaglandin E-2 and leukotriene B-4 concentrations in HIV-1 Tg but not wildtype rats. Thromboxane B-2, 15-HETE, lipoxin A4 and resolvin D-1 concentrations were unaffected by genotype or treatment. Conclusion: Chronic low-dose ASA reduces AA-metabolite markers of neuroinflammation and oxidative stress in a rat model for HAND. Published by Elsevier Ltd. C1 [Blanchard, Helene C.; Taha, Ameer Y.; Rapoport, Stanley I.; Yuan, Zhi-Xin] NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bldg 9,Room 1S128,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sir@mail.nih.gov FU Intramural Research Program of the National Institute on Aging FX The authors thank Lisa Chang and Mei Chen for skillful technical assistance. The research was supported by the Intramural Research Program of the National Institute on Aging. The authors declare no conflict of interest. NR 65 TC 5 Z9 6 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 EI 1532-2823 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD MAY PY 2015 VL 96 BP 25 EP 30 DI 10.1016/j.plefa.2015.01.002 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA CH0RV UT WOS:000353731000004 PM 25638779 ER PT J AU Tandon, M Gallo, A Jang, S Cotrim, A Alevizos, I AF Tandon, M. Gallo, A. Jang, S. Cotrim, A. Alevizos, I. TI Metagenomic Analysis of Salivary Exosome Transcriptomes from Patients with Primary Sjogren's Syndrome Using RNA-Seq SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Sjogren's Syndrome CY MAY 19-22, 2015 CL Bergen, NORWAY C1 [Tandon, M.; Gallo, A.; Jang, S.; Cotrim, A.; Alevizos, I.] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-9475 EI 1365-3083 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAY PY 2015 VL 81 IS 5 MA S3.14 BP 351 EP 351 PG 1 WC Immunology SC Immunology GA CG6HV UT WOS:000353401300049 ER PT J AU Teos, L Zhang, J Hak, J Swaim, W Ambrus, J Grisius, M Cotrim, A Jang, S Bebris, L Illei, G Yule, D Ambudkar, I Alevizos, I AF Teos, L. Zhang, J. Hak, J. Swaim, W. Ambrus, J. Grisius, M. Cotrim, A. Jang, S. Bebris, L. Illei, G. Yule, D. Ambudkar, I. Alevizos, I. TI IP3R Deficit in Acinar Cells Underlies Loss of Salivary Gland Fluid Secretion in the Autoimmune Exocrinopathy, Sjogren's Syndrome SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Sjogren's Syndrome CY MAY 19-22, 2015 CL Bergen, NORWAY C1 [Teos, L.; Grisius, M.; Cotrim, A.; Jang, S.; Bebris, L.; Illei, G.; Alevizos, I.] NIDCR, Sjogrens Syndrome & Salivary Gland Dysfunct Unit, MPTB, NIH, Bethesda, MD 20892 USA. [Teos, L.; Swaim, W.; Ambudkar, I.] NIDCR, Secretory & Physiol Sect, MPTB, NIH, Bethesda, MD 20892 USA. [Zhang, J.; Hak, J.; Yule, D.] Univ Rochester, Med Ctr, Sch Med & Dent, Rochester, NY 14642 USA. [Ambrus, J.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Med, Div Allergy Immunol & Rheumatol, Buffalo, NY 14203 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-9475 EI 1365-3083 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAY PY 2015 VL 81 IS 5 MA S4.11 BP 359 EP 360 PG 2 WC Immunology SC Immunology GA CG6HV UT WOS:000353401300066 ER PT J AU Lai, Z Yin, H Cabrera-Perez, J Glenton, P Patel, A Swaim, W Zheng, C Nguyen, CQ Nyberg, F Chiorini, JA AF Lai, Z. Yin, H. Cabrera-Perez, J. Glenton, P. Patel, A. Swaim, W. Zheng, C. Nguyen, C. Q. Nyberg, F. Chiorini, J. A. TI Aquaporin Gene Therapy Corrects Exocrine Gland Dysfunction and Inflammation in Mouse Model of Sjogren's Syndrome SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Sjogren's Syndrome CY MAY 19-22, 2015 CL Bergen, NORWAY C1 [Lai, Z.; Yin, H.; Cabrera-Perez, J.; Patel, A.; Swaim, W.; Zheng, C.; Chiorini, J. A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. [Lai, Z.; Nyberg, F.] Uppsala Univ, Div Biol Res Drug Dependence, Dept Pharmaceut Biosci, S-75124 Uppsala, Sweden. [Glenton, P.; Nguyen, C. Q.] Univ Florida, Dept Pathol & Infect Dis, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-9475 EI 1365-3083 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAY PY 2015 VL 81 IS 5 MA S12.6 BP 423 EP 423 PG 1 WC Immunology SC Immunology GA CG6HV UT WOS:000353401300188 ER PT J AU Perez, P Teos, L Tandon, M Kazmi, S Gallo, A Illei, G Alevizos, I AF Perez, P. Teos, L. Tandon, M. Kazmi, S. Gallo, A. Illei, G. Alevizos, I. TI Downregulation of MicroRNA-183 in Sjogren's Syndrome Minor Salivary Glands; Implications in the Control of ezrin Expression and Salivary Gland Function SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Sjogren's Syndrome CY MAY 19-22, 2015 CL Bergen, NORWAY C1 [Perez, P.; Teos, L.; Tandon, M.; Kazmi, S.; Gallo, A.; Illei, G.; Alevizos, I.] NIDCR, MPTB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-9475 EI 1365-3083 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAY PY 2015 VL 81 IS 5 MA S12.11 BP 426 EP 426 PG 1 WC Immunology SC Immunology GA CG6HV UT WOS:000353401300193 ER PT J AU Weller, ML Gardener, MR Bogus, ZC Smith, MA Astorri, E Michael, DG Michael, DA Zheng, C Burbelo, PD Lai, Z Wilson, PA Swaim, W Handelman, B Afione, SA Bombardieri, M Chiorini, JA AF Weller, M. L. Gardener, M. R. Bogus, Z. C. Smith, M. A. Astorri, E. Michael, D. G. Michael, D. A. Zheng, C. Burbelo, P. D. Lai, Z. Wilson, P. A. Swaim, W. Handelman, B. Afione, S. A. Bombardieri, M. Chiorini, J. A. TI Hepatitis Delta Virus Detected in Salivary Glands of Sjogren's Syndrome Patients and Induces a Sjogren's Syndrome Phenotype in vivo SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Sjogren's Syndrome CY MAY 19-22, 2015 CL Bergen, NORWAY C1 [Weller, M. L.; Gardener, M. R.; Bogus, Z. C.; Smith, M. A.; Michael, D. G.; Zheng, C.; Lai, Z.; Swaim, W.; Handelman, B.; Afione, S. A.; Chiorini, J. A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. [Astorri, E.; Bombardieri, M.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Ctr Expt Med & Rheumatol, London, England. [Burbelo, P. D.] Natl Inst Dent & Craniofacial Res, Dent Clin Res Core, NIH, Bethesda, MD USA. [Wilson, P. A.] NIH, Natl Intramural Database, Div Enterprise & Custom Applicat, Ctr Informat Technol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-9475 EI 1365-3083 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAY PY 2015 VL 81 IS 5 MA S12.13 BP 427 EP 427 PG 1 WC Immunology SC Immunology GA CG6HV UT WOS:000353401300195 ER PT J AU Faustman, DL Alevizos, I AF Faustman, D. L. Alevizos, I. TI Investigation of Repeat BCG Vaccinations in Autoimmunity: Rationale and Phase I Trial in Sjogren's Syndrome SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Sjogren's Syndrome CY MAY 19-22, 2015 CL Bergen, NORWAY C1 [Faustman, D. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Immunobiol Lab, Boston, MA USA. [Alevizos, I.] NIDCR, Sjogrens Syndrome Clin, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-9475 EI 1365-3083 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAY PY 2015 VL 81 IS 5 MA S13.3 BP 428 EP 429 PG 2 WC Immunology SC Immunology GA CG6HV UT WOS:000353401300198 ER PT J AU Jang, SI Ong, HL Alevizos, I Ambudkar, IS AF Jang, S-I Ong, H-L Alevizos, I. Ambudkar, I. S. TI Calcium-Calcineurin-NFAT Signaling Pathway Regulates AQP5 Expression in Primary Salivary Gland Acinar Cells SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Sjogren's Syndrome CY MAY 19-22, 2015 CL Bergen, NORWAY C1 [Jang, S-I; Alevizos, I.] NIDCR, Sjogrens Syndrome & Salivary Gland Dysfunct Unit, MPTB, NIH, Bethesda, MD 20892 USA. [Jang, S-I; Ong, H-L; Ambudkar, I. S.] NIDCR, Secretory & Physiol Sect, MPTB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-9475 EI 1365-3083 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAY PY 2015 VL 81 IS 5 MA S13.8 BP 431 EP 431 PG 1 WC Immunology SC Immunology GA CG6HV UT WOS:000353401300203 ER PT J AU Insel, TR Cuthbert, BN AF Insel, Thomas R. Cuthbert, Bruce N. TI Brain disorders? Precisely SO SCIENCE LA English DT Editorial Material ID RESEARCH DOMAIN CRITERIA; MENTAL-DISORDERS; MEDICINE; HEALTH C1 [Insel, Thomas R.; Cuthbert, Bruce N.] NIMH, NIH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. EM tinsel@mail.nih.gov NR 15 TC 55 Z9 56 U1 3 U2 26 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAY 1 PY 2015 VL 348 IS 6234 BP 499 EP 500 DI 10.1126/science.aab2358 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH1JR UT WOS:000353778100020 PM 25931539 ER PT J AU Palesch, YY Yeatts, SD Tomsick, TA Foster, LD Demchuk, AM Khatri, P Hill, MD Jauch, EC Jovin, TG Yan, B von Kummer, R Molina, CA Goyal, M Schonewille, WJ Mazighi, M Engelter, ST Anderson, C Spilker, J Carrozzella, J Ryckborst, KJ Janis, LS Simpson, A Simpson, KN Broderick, JP AF Palesch, Yuko Y. Yeatts, Sharon D. Tomsick, Thomas A. Foster, Lydia D. Demchuk, Andrew M. Khatri, Pooja Hill, Michael D. Jauch, Edward C. Jovin, Tudor G. Yan, Bernard von Kummer, Ruediger Molina, Carlos A. Goyal, Mayank Schonewille, Wouter J. Mazighi, Mikael Engelter, Stefan T. Anderson, Craig Spilker, Judith Carrozzella, Janice Ryckborst, Karla J. Janis, L. Scott Simpson, Annie Simpson, Kit N. Broderick, Joseph P. CA Interventional Management Stroke I TI Twelve-Month Clinical and Quality-of-Life Outcomes in the Interventional Management of Stroke III Trial SO STROKE LA English DT Article DE acute stroke; endovascular procedures; randomized trial; tPA ID ACUTE ISCHEMIC-STROKE; ENDOVASCULAR THERAPY; RANDOMIZED-TRIAL; POOLED ANALYSIS; TIME; EQ-5D; SCORE; RECANALIZATION; THROMBECTOMY; REPERFUSION AB Background and Purpose-Randomized trials have indicated a benefit for endovascular therapy in appropriately selected stroke patients at 3 months, but data regarding outcomes at 12 months are currently lacking. Methods-We compared functional and quality-of-life outcomes at 12 months overall and by stroke severity in stroke patients treated with intravenous tissue-type plasminogen activator followed by endovascular treatment as compared with intravenous tissue-type plasminogen activator alone in the Interventional Management of Stroke III Trial. The key outcome measures were a modified Rankin Scale score <= 2 (functional independence) and the Euro-QoL EQ-5D, a health-related quality-of-life measure. Results-656 subjects with moderate-to-severe stroke (National Institutes of Health Stroke Scale >= 8) were enrolled at 58 centers in the United States (41 sites), Canada (7), Australia (4), and Europe (6). There was an interaction between treatment group and stroke severity in the repeated measures analysis of modified Rankin Scale <= 2 outcome (P=0.039). In the 204 participants with severe stroke (National Institutes of Health Stroke Scale >= 20), a greater proportion of the endovascular group had a modified Rankin Scale <= 2 (32.5%) at 12 months as compared with the intravenous tissue-type plasminogen activator group (18.6%, P=0.037); no difference was seen for the 452 participants with moderately severe strokes (55.6% versus 57.7%). In participants with severe stroke, the endovascular group had 35.2 (95% confidence interval: 2.1, 73.3) more quality-adjusted-days over 12 months as compared with intravenous tissue-type plasminogen activator alone. Conclusions-Endovascular therapy improves functional outcome and health-related quality-of-life at 12 months after severe ischemic stroke. C1 [Tomsick, Thomas A.; Khatri, Pooja; Spilker, Judith; Carrozzella, Janice; Broderick, Joseph P.] Univ Cincinnati, Dept Neurol, Inst Neurosci, Acad Hlth Ctr, Cincinnati, OH 45267 USA. [Tomsick, Thomas A.; Khatri, Pooja; Spilker, Judith; Carrozzella, Janice; Broderick, Joseph P.] Univ Cincinnati, Dept Rehabil Med & Radiol, Inst Neurosci, Acad Hlth Ctr, Cincinnati, OH 45267 USA. [Palesch, Yuko Y.; Yeatts, Sharon D.; Foster, Lydia D.; Simpson, Annie; Simpson, Kit N.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC USA. [Jauch, Edward C.] Med Univ S Carolina, Div Emergency Med, Charleston, SC USA. [Demchuk, Andrew M.; Hill, Michael D.; Goyal, Mayank; Ryckborst, Karla J.] Univ Calgary, Dept Clin Neurosci, Seaman Family MR Res Ctr, Calgary Stroke Program,Hotchkiss Brain Inst, Calgary, AB, Canada. [Demchuk, Andrew M.; Hill, Michael D.; Goyal, Mayank; Ryckborst, Karla J.] Univ Calgary, Dept Radiol, Seaman Family MR Res Ctr, Calgary Stroke Program,Hotchkiss Brain Inst, Calgary, AB, Canada. [Jovin, Tudor G.] Univ Pittsburgh, Med Ctr, Stroke Inst, Pittsburgh, PA USA. [Yan, Bernard] Univ Melbourne, Royal Melbourne Hosp, Melbourne Brain Ctr, Melbourne, Vic 3050, Australia. [von Kummer, Ruediger] Dresden Univ, Stroke Ctr, Dept Neuroradiol, Univ Hosp, Dresden, Germany. [Molina, Carlos A.] Hosp Univ Vall Hebron, Dept Neurol, Neurovasc Unit, Barcelona, Spain. [Schonewille, Wouter J.] Univ Med Ctr Utrecht, Dept Neurol, Utrecht, Netherlands. [Schonewille, Wouter J.] Rudolf Magnus Inst Neurosci, NL-3508 TA Utrecht, Netherlands. [Schonewille, Wouter J.] St Antonius Hosp, Nieuwegein, Netherlands. [Mazighi, Mikael] Lariboisiere Hosp, Dept Neurol, Paris, France. [Mazighi, Mikael] Lariboisiere Hosp, Stroke Ctr, Paris, France. [Engelter, Stefan T.] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland. [Anderson, Craig] Univ Sydney, Royal Prince Alfred Hosp, George Inst Global Hlth, Sydney, NSW 2006, Australia. [Janis, L. Scott] NINDS, NIH, Bethesda, MD 20892 USA. RP Broderick, JP (reprint author), Univ Cincinnati, Dept Neurol, Inst Neurosci, 260 Stetson St,Suite 2300,POB 670525, Cincinnati, OH 45267 USA. EM joseph.broderick@uc.edu FU National Institute of Health/NINDS [U01NS052220, U01NS054630, U01NS077304] FX National Institute of Health/NINDS Grant Numbers: University of Cincinnati U01NS052220 and Medical University of South Carolina U01NS054630 and U01NS077304. Genentech Inc. supplied study drug used for intra-arterial tPA in the Endovascular group. EKOS Corp., Concentric Inc., Cordis Neurovascular, Inc. supplied study catheters during Protocol Versions 1-3. In the United States, IMS III investigator meeting support was provided in part by Genentech Inc, EKOS Corp., and Concentric Inc. In Europe, IMS III investigator meeting support was provided in part by Boehringer Ingelheim. Y.Y. Palesch, S.D. Yeatts, L.D. Foster, A. Simpson, K.N. Simpson, J.P. Broderick were responsible for the analyses used in this article. Y.Y. Palesch and J.P. Broderick had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 33 TC 5 Z9 5 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAY PY 2015 VL 46 IS 5 BP 1321 EP 1327 DI 10.1161/STROKEAHA.115.009180 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CG8LR UT WOS:000353559800044 PM 25858239 ER PT J AU Abdul-Rahim, AH Fulton, RL Sucharew, H Kleindorfer, D Khatri, P Broderick, JP Lees, KR AF Abdul-Rahim, A. H. Fulton, R. L. Sucharew, H. Kleindorfer, D. Khatri, P. Broderick, J. P. Lees, K. R. CA VISTA Collaborators TI National Institutes of Health Stroke Scale Item Profiles as Predictor of Patient Outcome: External Validation on Independent Trial Data (vol 46, pg 395, 2015) SO STROKE LA English DT Correction C1 [Abdul-Rahim, A. H.; Fulton, R. L.; Sucharew, H.; Kleindorfer, D.; Khatri, P.; Broderick, J. P.; Lees, K. R.] NIH, Bethesda, MD 20892 USA. RP Abdul-Rahim, AH (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. RI Sucharew, Heidi/M-4338-2015 NR 1 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAY PY 2015 VL 46 IS 5 BP E128 EP E128 DI 10.1161/STR.0000000000000066 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CG8LR UT WOS:000353559800014 ER PT J AU Degoma, EM Salavati, A Shinohara, RT Saboury, B Pollan, L Schoen, M Torigian, DA Mohler, ER Dunbar, RL Litt, HI Woo, J Rader, DJ Alavi, A Mehta, NN AF deGoma, Emil M. Salavati, Ali Shinohara, Russell T. Saboury, Babak Pollan, Laura Schoen, Marisa Torigian, Drew A. Mohler, Emile R. Dunbar, Richard L. Litt, Harold I. Woo, John Rader, Daniel J. Alavi, Abass Mehta, Nehal N. TI A Pilot Trial to Examine the Effect of High-Dose Niacin on Arterial Wall Inflammation Using Fluorodeoxyglucose Positron Emission Tomography SO ACADEMIC RADIOLOGY LA English DT Article DE Atherosclerosis; positron emission tomography; fluorodeoxyglucose; lipids; niacin ID ACUTE CORONARY SYNDROME; LOW-DENSITY-LIPOPROTEIN; ATHEROSCLEROTIC PLAQUE INFLAMMATION; TRANSIENT ISCHEMIC ATTACK; EXTENDED-RELEASE NIACIN; NICOTINIC-ACID; STATIN THERAPY; FDG-PET/CT; SECONDARY PREVENTION; RANDOMIZED-TRIALS AB Rationale and Objectives: Although studies have reported direct inhibition of inflammatory pathways with niacin, the effect of niacin on arterial wall inflammation remains unknown. We examined the effect of niacin on arterial F-18-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT). Materials and Methods: Nine statin-treated patients with coronary disease were randomized to niacin 6000 mg/day or placebo. FDG-PET/CT and lipids were assessed at-baseline and at 12 weeks. FOG was quantified in the aorta, right carotid artery, and left carotid artery as the target-to-background ratio (TBR) and target-to-background difference (TBD). Results: Eight patients completed the study. No significant changes in FOG measured by aortic, left carotid, or right carotid TBR or TBD were seen in either group. Compared to baseline, niacin-treated subjects exhibited a significant 29% reduction in low-density lipoprotein cholesterol (LDL-C; 95% confidence interval [CI], -50% to 8%; P = .01) and a nonsignificant 29% reduction in LDL particle number (LDL-P; 95% CI, -58% to 0.2%; P = .07). A nonsignificant 11% increase in HDL-C (95% CI, -15% to 37%; P = .30) and 8% decrease in HDL-P (95% CI, -44% to 28%; P = .51) were observed with niacin treatment. In a pooled analysis, changes in LDL-P were positively correlated with FOG uptake in the aorta (TBR r = 0.66, P = .08; TBD r = 0.75, P = .03), left carotid (TBR r = 0.65, P = .08; TBD r = 0.74, P = .03), and right carotid (TBR r = 0.54, P = .17; TBD r = 0.61, P = .11). Conclusions: In this pilot study, adding niacin to statin therapy did not affect arterial wall inflammation measured by FDG-PET/CT. However, an association between changes in arterial FOG uptake and LDL-P was observed. Larger studies are needed to definitively examine the effect of niacin on arterial wall inflammation. C1 [deGoma, Emil M.; Mohler, Emile R.] Univ Penn, Div Cardiovasc Med, Perelman Ctr Adv Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Salavati, Ali; Saboury, Babak; Torigian, Drew A.; Alavi, Abass] Univ Penn, Div Nucl Med, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Shinohara, Russell T.; Dunbar, Richard L.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Pollan, Laura; Schoen, Marisa; Rader, Daniel J.] Univ Penn, Div Translat Med & Human Genet, Perelman Sch Med, Philadelphia, PA 19104 USA. [Torigian, Drew A.; Litt, Harold I.; Woo, John] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Mehta, Nehal N.] NHLBI, Sect Inflammat & Cardiometab Dis, Bethesda, MD USA. RP Degoma, EM (reprint author), Univ Penn, Div Cardiovasc Med, Perelman Ctr Adv Med, Perelman Sch Med, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM deGoma@uphs.upenn.edu FU Perelman School of Medicine at the University of Pennsylvania Schiffrin Award; Division of Radiology Pilot Grant (PRODEV); Foundation of the National Lipid Association; Division of Intramural Research grant [HL-Z00000]; National Institute of Neurological Disorders and Stroke [R01NS085211] FX E.M.D. was supported by the Perelman School of Medicine at the University of Pennsylvania Schiffrin Award, the Division of Radiology Pilot Grant (PRODEV), and the Foundation of the National Lipid Association. N.N.M. was supported by the Division of Intramural Research grant HL-Z00000. R.T.S. was supported by R01NS085211 from the National Institute of Neurological Disorders and Stroke. NR 55 TC 1 Z9 1 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD MAY PY 2015 VL 22 IS 5 BP 600 EP 609 DI 10.1016/j.acra.2014.12.015 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CG2AZ UT WOS:000353078600008 PM 25708866 ER PT J AU Turkbey, B Hoyt, RF Agarwal, HK Bernardo, M Sankineni, S Johnson, L Grant, KB Rais-Bahrami, S Kobayashi, H Wood, BJ Pinto, PA Griffiths, GL Choyke, PL AF Turkbey, Baris Hoyt, Robert F., Jr. Agarwal, Harsh K. Bernardo, Marcelino Sankineni, Sandeep Johnson, Linda Grant, Kinzya B. Rais-Bahrami, Soroush Kobayashi, Hisataka Wood, Bradford J. Pinto, Peter A. Griffiths, Gary L. Choyke, Peter L. TI Magnetic Resonance Sentinel Lymph Node Imaging of the Prostate with Gadofosveset Trisodium-Albumin: Preliminary Results in a Canine Model SO ACADEMIC RADIOLOGY LA English DT Article DE Gadofosveset trisodium; lymph node; MRI; human serum albumin ID HUMAN SERUM-ALBUMIN; CANCER; DISSECTION; LYMPHOGRAPHY; METASTASES; CARCINOMA; SIZE; 3T; CT AB Rationale and Objectives: To determine if intraprostatic injection of gadofosveset trisodium mixed with human serum albumin (HSA) can identify sentinel lymph nodes (LNs) draining the prostate on magnetic resonance imaging (MRI) in a canine model. Materials and Methods: Three male canines weighing between 25.7 and 41.3 kg were anesthetized, placed in a 3-T MRI, and a needle was placed transrectally into one side of the prostate using a commercially available intrarectal needle guide. Gadofosveset trisodium pre-mixed with 10% HSA was then administered at doses ranging from 0.1 to 2.5 mL. T1W MRI was performed immediately after injection, and two readers evaluated images for visualization of LNs draining the prostate. Results: Intraprostatic injection of 0.2 mL gadofosveset trisodium premixed with HSA identified the draining periprostatic LNs in all cases. Delayed images demonstrated upper echelon nodes in the pelvis and the abdomen. Higher volume injections resulted in excessive periprostatic extravasation, whereas lower volume injections resulted in suboptimal visualization of LNs. Conclusions: We demonstrate that gadofosveset trisodium (premixed with 10% HSA) injected intraprostatically at 0.2 mL visualized LNs draining the prostate. This approach can be readily adapted for clinical applications such as sentinel LN imaging in prostate cancer patients before surgery. C1 [Turkbey, Baris; Agarwal, Harsh K.; Bernardo, Marcelino; Sankineni, Sandeep; Johnson, Linda; Grant, Kinzya B.; Kobayashi, Hisataka; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Hoyt, Robert F., Jr.] NHLBI, Lab Anim Med & Surg, NIH, Bethesda, MD 20892 USA. [Hoyt, Robert F., Jr.] Leidos Biomed Res Inc, Lab Anim Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA. [Agarwal, Harsh K.] Philips Res North Amer, Briarcliff Manor, NY USA. [Rais-Bahrami, Soroush; 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. [Wood, Bradford J.; Pinto, Peter A.] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Griffiths, Gary L.] Leidos Biomed Res Inc, Clin Res Directorate, Clin Monitoring Res Program, Frederick Natl Lab Canc Res, Frederick, MD USA. RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182 Bldg 10,Room B3B85, Bethesda, MD 20892 USA. EM turkbeyi@mail.nih.gov OI Rais-Bahrami, Soroush/0000-0001-9466-9925 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 24 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD MAY PY 2015 VL 22 IS 5 BP 646 EP 652 DI 10.1016/j.acra.2014.12.021 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CG2AZ UT WOS:000353078600014 PM 25683498 ER PT J AU Adeyemi, EI Giedd, JN Lee, NR AF Adeyemi, Elizabeth I. Giedd, Jay N. Lee, Nancy Raitano TI A Case Study of Brain Morphometry in Triplets Discordant for Down Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE down syndrome; trisomy 21; magnetic resonance imaging; cortical thickness; cortical surface area ID HIGH-RESOLUTION MRI; CHILDREN; GROWTH; CORTEX AB Down syndrome, the most common genetic cause of intellectual disability, offers the opportunity to explore the associations between genetics and both neuroanatomic and neuropsychological phenotypes. This case report summarizes the findings of a neuroimaging and neuropsychology study of two adolescent females with Down syndrome and their same-sex discordant triplet siblings (one from each family; n=4). Using high-resolution magnetic resonance imaging and surface based morphometric approaches, we offer the first in vivo report of cortical surface area reductions and increases in the thickness of the cortical sheet in youth with Down syndrome relative to their typically developing same-sex triplet siblings. (c) 2015 Wiley Periodicals, Inc. C1 [Adeyemi, Elizabeth I.; Giedd, Jay N.; Lee, Nancy Raitano] NIMH, Sect Brain Imaging, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Giedd, Jay N.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Lee, Nancy Raitano] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. RP Adeyemi, EI (reprint author), NIMH, Child Psychiat Branch, NIH, 10 Ctr Dr,Bldg 10,Room 4C110,MSC 1367, Bethesda, MD 20892 USA. EM eadeyemi1@gmail.com RI Giedd, Jay/J-9644-2015; Lee, Nancy/M-7492-2016 OI Giedd, Jay/0000-0003-2002-8978; Lee, Nancy/0000-0002-6663-0713 FU National Institutes of Health, National Institute of Mental Health [NCT00001246, 89-M-0006] FX Grant sponsor: National Institutes of Health, National Institute of Mental Health; Grant number: NCT00001246; Protocol ID 89-M-0006. NR 20 TC 0 Z9 0 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAY PY 2015 VL 167 IS 5 BP 1107 EP 1110 DI 10.1002/ajmg.a.36820 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA CG3HY UT WOS:000353171900019 PM 25820455 ER PT J AU van Ravesteyn, NT van Lier, L Schechter, CB Ekwueme, DU Royalty, J Miller, JW Near, AM Cronin, KA Heijnsdijk, EAM Mandelblatt, JS de Koning, HJ AF van Ravesteyn, Nicolien T. van Lier, Lisanne Schechter, Clyde B. Ekwueme, Donatus U. Royalty, Janet Miller, Jacqueline W. Near, Aimee M. Cronin, Kathleen A. Heijnsdijk, Eveline A. M. Mandelblatt, Jeanne S. de Koning, Harry J. TI Transition From Film to Digital Mammography Impact for Breast Cancer Screening Through the National Breast and Cervical Cancer Early Detection Program SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID COST-EFFECTIVENESS; RANDOMIZED-TRIALS; UNITED-STATES; INSURANCE STATUS; RACE; PERFORMANCE; BENEFITS; WOMEN; RATES; CONSEQUENCES AB Introduction: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides mammograms and diagnostic services for low-income, uninsured women aged 40-64 years. Mammography facilities within the NBCCEDP gradually shifted from plain-film to digital mammography. The purpose of this study is to assess the impact of replacing film with digital mammography on health effects (deaths averted, life-years gained [LYG]); costs (for screening and diagnostics); and number of women reached. Methods: NBCCEDP 2010 data and data representative of the program's target population were used in two established microsimulation models. Models simulated observed screening behavior including different screening intervals (annual, biennial, irregular) and starting ages (40, 50 years) for white, black, and Hispanic women. Model runs were performed in 2012. Results: The models predicted 8.0-8.3 LYG per 1,000 film screens for black women, 5.9-7.5 for white women, and 4.0-4.5 for Hispanic women. For all race/ethnicity groups, digital mammography had more LYG than film mammography (2%-4%), but had higher costs (34%-35%). Assuming a fixed budget, 25%-26% fewer women could be served, resulting in 22%-24% fewer LYG if all mammograms were converted to digital. The loss in LYG could be reversed to an 8%-13% increase by only including biennial screening. Conclusions: Digital could result in slightly more LYG than film mammography. However, with a fixed budget, fewer women may be served with fewer LYG. Changes in the program, such as only including biennial screening, will increase LYG/screen and could offset the potential decrease in LYG when shifting to digital mammography. (C) 2015 American Journal of Preventive Medicine. All rights reserved. C1 [van Ravesteyn, Nicolien T.; van Lier, Lisanne; Heijnsdijk, Eveline A. M.; de Koning, Harry J.] Univ Med Ctr, Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands. [van Lier, Lisanne] Vrije Univ Amsterdam, Dept Gen Practice & Elderly Care Med, Med Ctr, Amsterdam, Netherlands. [Schechter, Clyde B.] Albert Einstein Coll Med, Dept Family & Social Med, Bronx, NY USA. [Schechter, Clyde B.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY USA. [Ekwueme, Donatus U.; Royalty, Janet; Miller, Jacqueline W.] CDC, Atlanta, GA 30333 USA. [Near, Aimee M.; Mandelblatt, Jeanne S.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA. [Cronin, Kathleen A.] NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP van Ravesteyn, NT (reprint author), Erasmus MC, Dept Publ Hlth, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM n.vanravesteyn@erasmusmc.nl FU National Cancer Institute (NCI)-funded Breast Cancer Surveillance Consortium [HHSN261201100031C]; Interagency Agreement from CDC to the NCI [U01CA115337-10S1]; NCI [U01CA152958, U01CA088283, KO5CA96940]; Department of Defense [BC043120] FX We thank the National Comprehensive Cancer Network investigators for use of data on treatment dissemination. We thank the Breast Cancer Surveillance Consortium (BCSC) investigators for the data they have provided for this study. BCSC data collection was supported by the National Cancer Institute (NCI)-funded Breast Cancer Surveillance Consortium (Grant No. HHSN261201100031C). A list of the BCSC investigators and procedures for requesting BCSC data for research purposes are provided at: breastscreening.cancer.gov/. Drs. Mandelblatt and de Koning contributed equally to this work as senior authors. This study was supported by an Interagency Agreement from CDC to the NCI and funded under Grant No. U01CA115337-10S1.; This study was also supported in part by the NCI (Grant Nos. U01CA152958, U01CA088283; grant No. KO5CA96940 [JM]) and the Department of Defense (Grant No. BC043120 [JM]). Model results are the sole responsibility of the authors. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of CDC. NR 33 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2015 VL 48 IS 5 BP 535 EP 542 DI 10.1016/j.amepre.2014.11.010 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA CG1XO UT WOS:000353069300008 PM 25891052 ER PT J AU Chattopadhyay, PK Roederer, M AF Chattopadhyay, P. K. Roederer, M. TI A Mine Is a Terrible Thing to Waste: High Content, Single Cell Technologies for Comprehensive Immune Analysis SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review ID HUMAN T-CELLS; POLYCHROMATIC FLOW-CYTOMETRY; MASS CYTOMETRY; PHENOTYPIC ANALYSIS; GENE-EXPRESSION; RESPONSES; HETEROGENEITY; QUALITY; SUBSET; VISUALIZATION AB In recent years, an incredible variety of single cell technologies have become available to analyze immune responses. These technologies include polychromatic flow cytometry, mass cytometry, highly multiplexed single cell qPCR, RNA sequencing, microtools, and high-resolution imaging. In this article, we review these platforms, describing their power and limitations for comprehensive analysis of the immune system. We relate the properties of these technologies to the various cellular states relevant to an immune response, in order to address which technologies are most appropriate for which settings. C1 [Chattopadhyay, P. K.; Roederer, M.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Chattopadhyay, PK (reprint author), NIH, Vaccine Res Ctr, Bldg 10, Bethesda, MD 20892 USA. OI Chattopadhyay, Pratip/0000-0002-5457-9666 NR 60 TC 6 Z9 6 U1 0 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2015 VL 15 IS 5 BP 1155 EP 1161 DI 10.1111/ajt.13193 PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA CG5ML UT WOS:000353335900008 PM 25708158 ER PT J AU Smith, MC Crist, RM Clogston, JD McNeil, SE AF Smith, Mackensie C. Crist, Rachael M. Clogston, Jeffrey D. McNeil, Scott E. TI Quantitative analysis of PEG-functionalized colloidal gold nanoparticles using charged aerosol detection SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Polyethylene glycol (PEG); Surface characterization; Charged aerosol detector; Gold nanoparticles; Stability; Displacement; Dissolution ID POLYETHYLENE-GLYCOL; COLORIMETRIC ASSAY; CANCER-THERAPY; PARTICLE-SIZE; SURFACE; QUANTIFICATION; PEGYLATION; PHARMACOKINETICS; PHARMACEUTICALS; TRANSLATION AB Surface characteristics of a nanoparticle, such as functionalization with polyethylene glycol (PEG), are critical to understand and achieve optimal biocompatibility. Routine physicochemical characterization such as UV-vis spectroscopy (for gold nanoparticles), dynamic light scattering, and zeta potential are commonly used to assess the presence of PEG. However, these techniques are merely qualitative and are not sensitive enough to distinguish differences in PEG quantity, density, or presentation. As an alternative, two methods are described here which allow for quantitative measurement of PEG on PEGylated gold nanoparticles. The first, a displacement method, utilizes dithiothreitol to displace PEG from the gold surface. The dithiothreitol-coated gold nanoparticles are separated from the mixture via centrifugation, and the excess dithiothreitol and dissociated PEG are separated through reversed-phase high-performance liquid chromatography (RP-HPLC). The second, a dissolution method, utilizes potassium cyanide to dissolve the gold nanoparticles and liberate PEG. Excess CN-, Au(CN)(2) (-), and free PEG are separated using RP-HPLC. In both techniques, the free PEG can be quantified against a standard curve using charged aerosol detection. The displacement and dissolution methods are validated here using 2-, 5-, 10-, and 20-kDa PEGylated 30-nm colloidal gold nanoparticles. Further value in these techniques is demonstrated not only by quantitating the total PEG fraction but also by being able to be adapted to quantitate the free unbound PEG and the bound PEG fractions. This is an important distinction, as differences in the bound and unbound PEG fractions can affect biocompatibility, which would not be detected in techniques that only quantitate the total PEG fraction. C1 [Smith, Mackensie C.; Crist, Rachael M.; Clogston, Jeffrey D.; McNeil, Scott E.] Leidos Biomed Res Inc, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Clogston, JD (reprint author), Leidos Biomed Res Inc, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM clogstonj@mail.nih.gov RI Crist, Rachael/K-7603-2012; Nanotechnology Characterization Lab, NCL/K-8454-2012 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX The authors are grateful to Sarah Anderson, Matthew Hansen, and Simona Colantonio for TEM, ICP-MS, and MALDI-TOF MS analysis, respectively, and Joseph Meyer for graphic illustrations. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 48 TC 5 Z9 5 U1 5 U2 55 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 EI 1618-2650 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD MAY PY 2015 VL 407 IS 13 BP 3705 EP 3716 DI 10.1007/s00216-015-8589-2 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA CG4CS UT WOS:000353230400016 PM 25749798 ER PT J AU Kaplan, RM Howard, VJ Safford, MM Howard, G AF Kaplan, Robert M. Howard, Virginia J. Safford, Monika M. Howard, George TI Educational attainment and longevity: results from the REGARDS US national cohort study of blacks and whites SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Educational attainment; Life expectancy; All-cause mortality; Prospective cohort ID HEALTHY LIFE EXPECTANCY; ADULT MORTALITY; UNITED-STATES; RISK-FACTORS; AGE; COUNTRIES; INEQUALITIES; GRADIENT; GENDER; INCOME AB Background: Educational attainment may be an important determinant of life expectancy. However, few studies have prospectively evaluated the relationship between educational attainment and life expectancy using adjustments for other social, behavioral, and biological factors. Method: The data were from the REasons for Geographic and Racial Differences in Stroke study that enrolled 30,239 black and white adults (>= 45 years) between 2003 and 2007. Demographic and cardiovascular risk information was collected and participants were followed for health outcomes. Educational attainment was categorized as less than high school education, high school graduate, some college, or college graduate. Proportional hazards analysis was used to characterize survival by level of education. Results: Educational attainment and follow-up data were available on 29,657(98%) of the participants. Over 6.3 years of follow-up, 3673 participants died. There was a monotonically increasing risk of death with lower levels of educational attainment. The same monotonic relationship held with adjustments for age, race, sex, cardiovascular risk factors, and health behaviors. The unadjusted hazard ratio for those without a high school education in comparison with college graduates was 2.89 (95% CI =2.64-3.18). Although adjustment for income, health behaviors, and cardiovascular risk factors attenuated the relationship, the same consistent pattern was observed after adjustment. The relationship between educational attainment and longevity was similar for black and white participants. The monotonic relationship between educational attainment and longevity was observed for all age groups, except for those aged 85 years or more. Conclusions: Educational attainment is a significant predictor of longevity. Other factors including age, race, income, health behaviors, and cardiovascular risk factors only partially explain the relationship. Published by Elsevier Inc. C1 [Kaplan, Robert M.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Howard, Virginia J.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Safford, Monika M.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Howard, George] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. RP Kaplan, RM (reprint author), Agcy Healthcare Res & Qual, 540 Gaither Rd, Rockville, MD 20850 USA. EM rmkaplan@ucla.edu FU National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH) [U01 NS041588]; American Reinvestment and Recovery Act supplement; Department of Health and Human Services FX This research was supported by a cooperative agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH), Department of Health and Human Services, and also an American Reinvestment and Recovery Act supplement. The content is solely the responsibility of the authors and does not necessarily represent the official views and positions of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health. NR 25 TC 2 Z9 3 U1 3 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAY PY 2015 VL 25 IS 5 BP 323 EP 328 DI 10.1016/j.annepidem.2015.01.017 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CG5XI UT WOS:000353368800003 PM 25791026 ER PT J AU Alonso, A Huang, XM Mosley, TH Heiss, G Chen, HL AF Alonso, Alvaro Huang, Xuemei Mosley, Thomas H. Heiss, Gerardo Chen, Honglei TI Heart Rate Variability and the Risk of Parkinson Disease: The Atherosclerosis Risk in Communities Study SO ANNALS OF NEUROLOGY LA English DT Article ID PATHOPHYSIOLOGY; DEGENERATION AB ObjectiveAutonomic dysfunction frequently occurs in the context of Parkinson disease (PD) and may precede onset of motor symptoms. Limited data exist on the prospective association of heart rate variability (HRV), a marker of autonomic function, with PD risk. MethodsWe included 12,162 participants of the Atherosclerosis Risk in Communities study, a community-based cohort, without a diagnosis of PD at baseline (1987-1989) and with available HRV data (mean age=54 years, 57% women). A 2-minute electrocardiogram was used to measure HRV. Incident PD was identified through 2008 from multiple sources, and adjudicated. Multivariable Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of PD by quartiles of HRV measurements. ResultsDuring a mean follow-up of 18 years, we identified 78 incident PD cases. Lower values of the root mean square of successive differences in normal-to-normal R-R intervals (rMSSD) and standard deviation of normal-to-normal R-R intervals (SDNN), markers of parasympathetic activity and total variability, respectively, were associated with higher PD risk during follow-up. In multivariate models, the HR (95% CI) of PD in the bottom quartiles of rMSSD and SDNN compared to the top quartiles were 2.1 (1.0-4.3) and 2.9 (1.4-6.1), respectively. Other measures of cardiac autonomic function, including mean R-R interval and frequency-domain measurements, were not associated with PD risk. InterpretationIn this prospective cohort, decreased HRV was associated with an increased risk of PD. Assessment of cardiac autonomic function may help identify individuals at risk for PD. Ann Neurol 2015;77:877-883 C1 [Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. [Huang, Xuemei] Penn State Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA USA. [Huang, Xuemei] Penn State Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA USA. [Huang, Xuemei] Penn State Milton S Hershey Med Ctr, Dept Pharmacol, Hershey, PA USA. [Huang, Xuemei] Penn State Milton S Hershey Med Ctr, Dept Radiol, Hershey, PA USA. [Huang, Xuemei] Penn State Milton S Hershey Med Ctr, Dept Kinesiol, Hershey, PA USA. [Huang, Xuemei] Penn State Milton S Hershey Med Ctr, Hershey Brain Anal Res Lab Neurodegenerat Disorde, Hershey, PA USA. [Mosley, Thomas H.] Univ Mississippi, Med Ctr, Div Geriatr Med, Jackson, MS 39216 USA. [Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Alonso, A (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM alonso@umn.edu RI Alonso, Alvaro/A-4917-2010; OI Alonso, Alvaro/0000-0002-2225-8323; Chen, Honglei/0000-0003-3446-7779 FU NIH National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; NIH, the National Institute of Environmental Health Sciences [Z01-ES101986]; NIH, National Institute of Neurological Diseases and Stroke [NS060722, NS082151]; National Institute of Environmental Health Sciences [ES019672]; National Institute of Aging [AG21491] FX The Atherosclerosis Risk in Communities study has been carried out as a collaborative study supported by NIH National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). This study was supported in part by the Intramural Program of the NIH, the National Institute of Environmental Health Sciences (Z01-ES101986). X.H. is currently supported by NIH, National Institute of Neurological Diseases and Stroke (NS060722 and NS082151), and National Institute of Environmental Health Sciences (ES019672), as well as a K23 award (National Institute of Aging (AG21491)) at the conception of this work. NR 22 TC 11 Z9 11 U1 0 U2 6 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 MAY PY 2015 VL 77 IS 5 BP 877 EP 883 DI 10.1002/ana.24393 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CG4EF UT WOS:000353235400015 PM 25707861 ER PT J AU Wang, T Cunningham, A Dokun, AO Hazarika, S Houston, K Chen, L Lye, RJ Spolski, R Leonard, WJ Annex, BH AF Wang, Tao Cunningham, Alexis Dokun, Ayotunde O. Hazarika, Surovi Houston, Kevin Chen, Lingdan Lye, R. John Spolski, Rosanne Leonard, Warren J. Annex, Brian H. TI Loss of Interleukin-21 Receptor Activation in Hypoxic Endothelial Cells Impairs Perfusion Recovery After Hindlimb Ischemia SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE peripheral arterial diseases; receptors, interleukin 21 ID PERIPHERAL ARTERIAL-DISEASE; CRITICAL LIMB ISCHEMIA; INTERMITTENT CLAUDICATION; THERAPEUTIC ANGIOGENESIS; GROWTH-FACTOR; PATHWAY; BIOLOGY; CANCER; MICE; INTERVENTION AB Objective-Surgical hindlimb ischemia (HLI) in mice has become a valuable preclinical model to study peripheral arterial disease. We previously identified that the different phenotypic outcomes after HLI across inbred mouse strains is related to a region on the short arm of mouse chromosome 7. The gene coding the interleukin-21 receptor (IL-21R) lies at the peak of association in this region. Approach and Results-With quantitative real-time polymerase chain reaction, we found that a mouse strain with a greater ability to upregulate IL-21R after HLI had better perfusion recovery than a strain with no upregulation after HLI. Immunofluorescent staining of ischemic hindlimb tissue showed IL-21R expression on endothelial cells (ECs) from C57BL/6 mice. An EC-enriched fraction isolated from ischemic hindlimb muscle showed higher Il-21R levels than an EC-enriched fraction from nonischemic limbs. In vitro, human umbilical vein ECs showed elevated IL-21R expression after hypoxia and serum starvation. Under these conditions, IL-21 treatment increased cell viability, decreased cell apoptosis, and augmented tube formation. In vivo, either knockout Il21r or blocking IL-21 signaling by treating with IL-21R-Fc (fusion protein that blocks IL-21 binding to its receptor) in C57BL/6 mice resulted in less perfusion recovery after HLI. Both in vitro and in vivo modulation of the IL-21/IL-21R axis under hypoxic conditions resulted in increased signal transducer and activator of transcription 3 phosphorylation and a subsequent increase in the B-cell lymphoma leukemia-2/BCL-2-associated X protein ratio. Conclusion-Our data indicate that IL-21R upregulation and ligand activation in hypoxic ECs may help perfusion recovery by limiting/preventing apoptosis and favoring cell survival and angiogenesis through the signal transducer and activator of transcription 3 pathway. C1 [Wang, Tao; Cunningham, Alexis; Dokun, Ayotunde O.; Hazarika, Surovi; Houston, Kevin; Chen, Lingdan; Lye, R. John; Annex, Brian H.] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA USA. [Hazarika, Surovi; Annex, Brian H.] Univ Virginia, Dept Med, Div Cardiovasc Med, Charlottesville, VA USA. [Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. [Spolski, Rosanne; Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA. RP Annex, BH (reprint author), Div Cardiovasc Med, POB 800158, Charlottesville, VA 22908 USA. EM annex@virginia.edu RI WANG, TAO/B-1888-2013 FU Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health; National Institutes of Health [RO1HL16455, RO1HL121635] FX W.J. Leonard and R. Spolski are supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health. B.H. Annex is supported by the National Institutes of Health RO1HL16455 and RO1HL121635. NR 41 TC 5 Z9 6 U1 0 U2 2 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 MAY PY 2015 VL 35 IS 5 BP 1218 EP 1225 DI 10.1161/ATVBAHA.115.305476 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CG5MF UT WOS:000353335300020 PM 25838422 ER PT J AU Gebreab, SY Riestra, P Khan, RJ Xu, RH Musani, SK Tekola-yele, F Correa, A Wilson, JG Rotimi, CN Davis, SK AF Gebreab, Samson Y. Riestra, Pia Khan, Rumana J. Xu, Ruihua Musani, Solomon K. Tekola-yele, Fasil Correa, Adolfo Wilson, James G. Rotimi, Charles N. Davis, Sharon K. TI Genetic Ancestry Is Associated With Measures of Subclinical Atherosclerosis in African Americans The Jackson Heart Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE African Americans; cardiovascular disease; epidemiology; genetic ancestry; subclinical atherosclerosis ID PERIPHERAL ARTERIAL-DISEASE; INTIMA-MEDIA THICKNESS; CARDIOVASCULAR RISK-FACTORS; BEAM COMPUTED-TOMOGRAPHY; ETHNIC-DIFFERENCES; CORONARY CALCIFICATION; CAROTID ATHEROSCLEROSIS; POPULATION; PREVALENCE; ADMIXTURE AB Objective-To determine whether genetic ancestry was associated with subclinical atherosclerosis measures after adjustment for traditional cardiovascular disease risk factors, inflammatory marker, socioeconomic status, and psychosocial factors in a large admixed African American population. Approach and Results-Participants were drawn from the Jackson Heart Study. Participant's percent of European ancestry (PEA) was estimated based on 1747 genetic markers using HAPMIX. Association of PEA with peripheral arterial disease and common carotid intima-media thickness were investigated among 2168 participants and with coronary artery calcification >0 and abdominal aortic calcification >0 among 1139 participants. The associations were evaluated using multivariable regression models. Our results showed that a 1 SD increase in PEA was associated with a lower peripheral arterial disease prevalence after adjusting for age and sex (prevalence ratio=0.90 [95% CI, 0.82-0.99]; P=0.036). Adjustments for traditional cardiovascular disease risk factors, socioeconomic status, and psychosocial factors attenuated this association (prevalence ratio=0.91 [0.82-1.00]; P=0.046). There was also a nonlinear association between PEA and coronary artery calcification and abdominal aortic calcification. The lowest PEA was associated with a lower coronary artery calcification (prevalence ratio=0.75 [0.58-0.96]; P=0.022) and a lower abdominal aortic calcification [prevalence ratio=0.80 [0.67-0.96]; P=0.016) compared with the reference group (10th-90th percentile) after adjusting for traditional cardiovascular disease risk factors, inflammatory marker, socioeconomic status, and psychosocial factors. However, we found no significant association between PEA and common carotid intima-media thickness. Conclusions-Overall, our findings indicate that genetic ancestry was associated with subclinical atherosclerosis, suggesting unmeasured risk factors and interactions with genetic factors might contribute to the distribution of subclinical atherosclerosis among African Americans. C1 [Gebreab, Samson Y.; Riestra, Pia; Khan, Rumana J.; Xu, Ruihua; Tekola-yele, Fasil; Rotimi, Charles N.; Davis, Sharon K.] NHGRI, Metab Cardiovasc & Inflammatory Dis Genom Branch, Bethesda, MD 20892 USA. [Musani, Solomon K.; Correa, Adolfo] Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS USA. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS USA. RP Gebreab, SY (reprint author), NHGRI, Metab Cardiovasc & Inflammatory Dis Genom Branch, 10 Ctr Dr,MSC 1644, Bethesda, MD 20892 USA. EM samson.gebreab@nih.gov OI Tekola-Ayele, Fasil/0000-0003-4194-9370 FU National Human Genomics Institute, National Institutes of Health; National Heart, Lung, and Blood Institute [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201 300049C, HHSN268201300050C]; National Institute on Minority Health and Health Disparities FX This research is supported by Intermural Program of National Human Genomics Institute, National Institutes of Health. The Jackson Heart Study is supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201 300049C, and HHSN268201300050C from the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities. NR 43 TC 4 Z9 4 U1 0 U2 0 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 MAY PY 2015 VL 35 IS 5 BP 1271 EP 1278 DI 10.1161/ATVBAHA.114.304855 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CG5MF UT WOS:000353335300026 PM 25745061 ER PT J AU Long, MT Wang, N Larson, MG Mitchell, GF Palmisano, J Vasan, RS Hoffmann, U Speliotes, EK Vita, JA Benjamin, EJ Fox, CS Hamburg, NM AF Long, Michelle T. Wang, Na Larson, Martin G. Mitchell, Gary F. Palmisano, Joseph Vasan, Ramachandran S. Hoffmann, Udo Speliotes, Elizabeth K. Vita, Joseph A. Benjamin, Emelia J. Fox, Caroline S. Hamburg, Naomi M. TI Nonalcoholic Fatty Liver Disease and Vascular Function Cross-Sectional Analysis in the Framingham Heart Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE multidetector computed tomography; obesity; risk factors; vascular endothelium ID INCREASED ARTERIAL STIFFNESS; FLOW-MEDIATED DILATION; ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR-DISEASE; HEPATIC STEATOSIS; RISK-FACTORS; SYSTEMIC INFLAMMATION; METABOLIC SYNDROME; NATURAL-HISTORY; ATHEROSCLEROSIS AB Objective-Patients with nonalcoholic fatty liver disease (NAFLD) have an increased risk of cardiovascular disease; however, it is not known whether NAFLD contributes to cardiovascular disease independent of established risk factors. We examined the association between NAFLD and vascular function. Approach and Results-We conducted a cross-sectional study of 2284 Framingham Heart Study participants without overt cardiovascular disease who had liver fat attenuation measured on computed tomography and who had measurements of vascular function and covariates. We evaluated the association between NAFLD and vascular function using multivariable partial correlations adjusting for age, sex, cohort, smoking, diabetes mellitus, hyperlipidemia, hypertension, body mass index, and visceral adipose tissue. The prevalence of NAFLD in our sample (mean age, 52 +/- 12 years; 51.4% women) was 15.3%. In age-, sex-, and cohort-adjusted analyses, greater liver fat was modestly associated with lower flow-mediated dilation (r=-0.05; P=0.02), lower peripheral arterial tonometry ratio (r=-0.20; P<0.0001), higher carotid-femoral pulse wave velocity (r=0.13; P<0.0001), and higher mean arterial pressure (r=0.11; P<0.0001). In multivariable-adjusted models, NAFLD remained associated with higher mean arterial pressure (r=0.06; P=0.005) and lower peripheral arterial tonometry ratio (r=-0.12; P<0.0001). The association between NAFLD and peripheral arterial tonometry ratio persisted after further adjustment for body mass index and visceral adipose tissue. Conclusions-For multiple measures of vascular function, the relationship with NAFLD appeared largely determined by shared cardiometabolic risk factors. The persistent relationship with reduced peripheral arterial tonometry response beyond established risk factors suggests that NAFLD may contribute to microvascular dysfunction. C1 [Long, Michelle T.] Boston Univ, Sch Med, Boston Med Ctr, Div Gastroenterol, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med, Dept Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Vita, Joseph A.; Hamburg, Naomi M.] Boston Univ, Sch Med, Evans Dept Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Vita, Joseph A.; Hamburg, Naomi M.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Long, Michelle T.; Larson, Martin G.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA USA. [Wang, Na; Palmisano, Joseph] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Speliotes, Elizabeth K.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Speliotes, Elizabeth K.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA. RP Hamburg, NM (reprint author), Boston Univ, Sch Med, Whitaker Cardiovasc Inst, 88 East Newton St,Suite C-818, Boston, MA 02118 USA. EM nhamburg@bu.edu OI Long, Michelle/0000-0001-6131-3981; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU Boston University School of Medicine; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; Division of Intramural Research of the National Heart, Lung, and Blood Institute; National Institutes of Health (NIH) [R01 AG047645-1, HL102299, 1R01HL60040, HL70100, HL076784, HL077447, HL107385]; Donald W. Reynolds Foundation; Boston University Clinical and Translational Science Institute [UL1-TR000157]; NIH [K23DK08145]; Doris Duke Foundation; Central Society for Clinical Research; Department of Internal Medicine at University of Michigan; BSSP program at University of Michigan FX This work was supported by the Boston University School of Medicine and the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract N01-HC-25195) and the Division of Intramural Research of the National Heart, Lung, and Blood Institute. The project was supported by National Institutes of Health (NIH) grants R01 AG047645-1, HL102299, 1R01HL60040; HL70100, HL076784, HL077447, HL107385 and the Donald W. Reynolds Foundation. Dr Long was supported in part by the Boston University Clinical and Translational Science Institute (grant UL1-TR000157). E. K. Speliotes was supported by NIH K23DK08145, The Doris Duke Foundation, Central Society for Clinical Research, and the Department of Internal Medicine and BSSP program at University of Michigan. NR 40 TC 13 Z9 13 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 MAY PY 2015 VL 35 IS 5 BP 1284 EP 1291 DI 10.1161/ATVBAHA.114.305200 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CG5MF UT WOS:000353335300028 PM 25745056 ER PT J AU Golin, J Ambudkar, SV AF Golin, John Ambudkar, Suresh V. TI The multidrug transporter Pdr5 on the 25th anniversary of its discovery: an important model for the study of asymmetric ABC transporters SO BIOCHEMICAL JOURNAL LA English DT Review DE asymmetric ABC transporter; molecular diode; Pdr5 ID NUCLEOTIDE-BINDING DOMAINS; INWARD-FACING CONFORMATION; MULTIPLE-DRUG RESISTANCE; P-GLYCOPROTEIN; SACCHAROMYCES-CEREVISIAE; CANDIDA-ALBICANS; ATP HYDROLYSIS; CASSETTE TRANSPORTER; CRYSTAL-STRUCTURE; MOLECULAR DIODE AB Asymmetric ABC (ATP-binding cassette) transporters make up a significant proportion of this important superfamily of integral membrane proteins. These proteins contain one canonical (catalytic) ATP-binding site and a second atypical site with little enzymatic capability. The baker's yeast (Saccharomyces cerevisiae) Pdr5 multidrug transporter is the founding member of the Pdr subfamily of asymmetric ABC transporters, which exist only in fungi and slime moulds. Because these organisms are of considerable medical and agricultural significance, Pdr5 has been studied extensively, as has its medically important homologue Cdr1 from Candida albicans. Genetic and biochemical analyses of Pdr5 have contributed important observations that are likely to be applicable to mammalian asymmetric ABC multidrug transporter proteins, including the basis of transporter promiscuity, the function of the non-catalytic deviant ATP-binding site, the most complete description of an in vivo transmission interface, and the recent discovery that Pdr5 is a molecular diode (one-way gate). In the present review, we discuss the observations made with Pdr5 and compare them with findings from clinically important asymmetric ABC transporters, such as CFTR (cystic fibrosis transmembrane conductance regulator), Cdr1 and Tap1/Tap2. C1 [Golin, John] Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. [Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Golin, J (reprint author), Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. EM golin@cua.edu FU National Science Foundation [MCB1048838]; National Institutes of Health [GM077211]; National Institutes of Health National Cancer Institute's Center for Cancer Research FX The work described in this review that was performed in the Golin laboratory was supported by National Science Foundation [grant number MCB1048838] and National Institutes of Health [grant number GM077211]. The many years of funding from these agencies is deeply appreciated. S.V.A. was supported by the Intramural Research Program of the National Institutes of Health National Cancer Institute's Center for Cancer Research. NR 71 TC 4 Z9 4 U1 3 U2 23 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 2015 VL 467 BP 353 EP 363 DI 10.1042/BJ20150042 PN 3 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CG3YX UT WOS:000353217200001 PM 25886173 ER PT J AU Nussinov, R Jang, H Tsai, CJ AF Nussinov, Ruth Jang, Hyunbum Tsai, Chung-Jung TI Oligomerization and nanocluster organization render specificity SO BIOLOGICAL REVIEWS LA English DT Review DE nanoclusters; signalling; oligomerization; structure; Ras; microclusters; cytoskeleton; allostery; conformational states; allosteric; scaffolding; co-localization ID RAS MEMBRANE ORIENTATION; SIGNAL-TRANSDUCTION; H-RAS; RECEPTOR SUPERFAMILY; SPATIAL-ORGANIZATION; KINASE DOMAIN; LIPID-BILAYER; K-RAS; N-RAS; CELL AB Nanoclusters are anchored to membranes, either within them or in the cytoplasm latched onto the cytoskeleton, whose reorganization can regulate their activity. Nanoclusters have been viewed in terms of cooperativity and activation; here we perceive nanocluster organization from a conformational standpoint. This leads us to suggest that while single molecules encode activity, nanoclusters induce specificity, and that this is their main evolutionary aim. Distinct, isoform-specific nanocluster organization can drive the preferred effector (and ligand) interactions and thereby designate signalling pathways. The absence of detailed structural information across the nanocluster, due to size and dynamics, hinders an in-depth grasp of its mechanistic features; however, available data already capture some of the principles and their functional 'raison d'etre'. Collectively, clustering lends stability and reduces the likelihood of proteolytic cleavage; it also increases the effective local concentration and enables efficient cooperative activation. However, clustering does not determine the ability of the single molecule to function. Drugs targeting nanoclusters can attenuate activity by hampering cooperativity; however, this may not perturb activation and signalling, which originate from the molecules themselves, and as such, are likely to endure. What then is the major role of nanoclustering? Assuming that single molecules evolved first, with a subsequent increase in cellular complexity and emergence of highly similar isoform variants, evolution faced the threat of signalling promiscuity. We reason that this potential risk was thwarted by oligomerization and clustering; clustering confers higher specificity, and a concomitant extra layer of cellular control. In our Ras example, signalling will be more accurate as a dimer than as a monomer, where its isomer specificity could be compromised. C1 [Nussinov, Ruth; Jang, Hyunbum; Tsai, Chung-Jung] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab, 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. RP Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab, Frederick, MD 21702 USA. EM NussinoR@helix.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the 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 86 TC 9 Z9 9 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-7931 EI 1469-185X J9 BIOL REV JI Biol. Rev. PD MAY PY 2015 VL 90 IS 2 BP 587 EP 598 DI 10.1111/brv.12124 PG 12 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CF8NL UT WOS:000352818700012 PM 24917483 ER PT J AU Kale, SS Jedhe, GS Meshram, SN Santra, MK Hamel, E Sanjayan, GJ AF Kale, Sangram S. Jedhe, Ganesh S. Meshram, Sachin N. Santra, Manas K. Hamel, Ernest Sanjayan, Gangadhar J. TI Novel hybrid nocodazole analogues as tubulin polymerization inhibitors and their antiproliferative activity SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Tubulin binding; Nocodazole; Colchicine; Anticancer ID COMBRETASTATIN A-4; COLCHICINE; AGENTS AB We describe the design, synthesis and SAR profiling of a series of novel combretastatin-nocodazole conjugates as potential anticancer agents. The thiophene ring in the nocodazole moiety was replaced by a substituted phenyl ring from the combretastatin moiety to design novel hybrid analogues. The hydroxyl group at the ortho position in compounds 2, 3 and 4 was used as the conformationally locking tool by anticipated six-membered hydrogen bonding. The bioactivity profiles of all compounds as tubulin polymerization inhibitors and as antiproliferative agents against the A-549 human lung cancer cell line were investigated Compounds 1 and 4 showed mu M IC50 values in both assays. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Kale, Sangram S.; Jedhe, Ganesh S.; Sanjayan, Gangadhar J.] CSIR Natl Chem Lab, Div Organ Chem, Pune 411008, Maharashtra, India. [Meshram, Sachin N.; Santra, Manas K.] Natl Ctr Cell Sci, Pune 411007, Maharashtra, India. [Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program,NIH, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA. RP Hamel, E (reprint author), NCI, Screening Technol Branch, Dev Therapeut Program,NIH, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA. EM gj.sanjayan@ncl.res.in RI Jedhe, Ganesh/M-9019-2015 OI Jedhe, Ganesh/0000-0001-7404-3677 FU CSIR, New Delhi; CSIR-Biodiversity programme [BSC-0120] FX S.S.K. and G.S.J. are thankful to CSIR, New Delhi, for a research fellowship. G.J.S. thanks CSIR-Biodiversity programme (BSC-0120) for funding this project. NR 20 TC 5 Z9 5 U1 1 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAY 1 PY 2015 VL 25 IS 9 BP 1982 EP 1985 DI 10.1016/j.bmcl.2015.03.019 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA CG3UL UT WOS:000353205000033 PM 25817588 ER PT J AU Jukic, AM AF Jukic, A. M. TI The impact of systematic errors on gestational age estimation SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Editorial Material C1 NIEHS, Durham, NC 27713 USA. RP Jukic, AM (reprint author), NIEHS, Durham, NC 27713 USA. FU Intramural NIH HHS NR 4 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD MAY PY 2015 VL 122 IS 6 BP 842 EP 842 DI 10.1111/1471-0528.13169 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CG4ZV UT WOS:000353299000013 PM 25377244 ER PT J AU Hong, CW Rais-Bahrami, S Walton-Diaz, A Shakir, N Su, D George, AK Merino, MJ Turkbey, B Choyke, PL Wood, BJ Pinto, PA AF Hong, Cheng W. Rais-Bahrami, Soroush Walton-Diaz, Annerleim Shakir, Nabeel Su, Daniel George, Arvin K. Merino, Maria J. Turkbey, Baris Choyke, Peter L. Wood, Bradford J. Pinto, Peter A. TI Comparison of magnetic resonance imaging and ultrasound (MRI-US) fusion-guided prostate biopsies obtained from axial and sagittal approaches SO BJU INTERNATIONAL LA English DT Article DE multiparametric MRI; fusion biopsy; prostate cancer ID CANCER-DETECTION; GLAND VOLUME; DIAGNOSIS; GUIDANCE AB Objective To compare cancer detection rates and concordance between magnetic resonance imaging and ultrasound (MRI-US) fusion-guided prostate biopsy cores obtained from axial and sagittal approaches. Patients and Methods Institutional records of MRI-US fusion-guided biopsy were reviewed. Detection rates for all cancers, Gleason >= 3 + 4 cancers, and Gleason >= 4 + 3 cancers were computed. Agreement between axial and sagittal cores for cancer detection, and frequency where one was upgraded the other was computed on a per-target and per-patient basis. Results In all, 893 encounters from 791 patients that underwent MRI-US fusion-guided biopsy in 2007-2013 were reviewed, yielding 4688 biopsy cores from 2344 targets for analysis. The mean age and PSA level at each encounter was 61.8 years and 9.7 ng/mL (median 6.45 ng/mL). Detection rates for all cancers, >= 3 + 4 cancers, and >= 4 + 3 cancers were 25.9%, 17.2%, and 8.1% for axial cores, and 26.1%, 17.6%, and 8.6% for sagittal cores. Per-target agreement was 88.6%, 93.0%, and 96.5%, respectively. On a per-target basis, the rates at which one core upgraded or detected a cancer missed on the other were 8.3% and 8.6% for axial and sagittal cores, respectively. Even with the inclusion of systematic biopsies, omission of axial or sagittal cores would have resulted in missed detection or under-characterisation of cancer in 4.7% or 5.2% of patients, respectively. Conclusion Cancer detection rates, Gleason scores, and core involvement from axial and sagittal cores are similar, but significant cancer may be missed if only one core is obtained for each target. Discordance between axial and sagittal cores is greatest in intermediate-risk scenarios, where obtaining multiple cores may improve tissue characterisation. C1 [Hong, Cheng W.; Wood, Bradford J.; Pinto, Peter A.] NCI, NIH, Ctr Intervent Oncol, Ctr Clin, Bethesda, MD 20892 USA. [Rais-Bahrami, Soroush; Walton-Diaz, Annerleim; Shakir, Nabeel; Su, Daniel; George, Arvin K.; Pinto, Peter A.] NCI, NIH, Urol Oncol Branch, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, NIH, Pathol Lab, Bethesda, MD 20892 USA. [Turkbey, Baris; Choyke, Peter L.] NCI, NIH, Mol Imaging Program, Bethesda, MD 20892 USA. RP Pinto, PA (reprint author), NCI, NIH, Urol Oncol Branch, CRC, 10 Ctr Dr,MSC 1210,Bldg 10,Rm 2W-5940, Bethesda, MD 20892 USA. EM pintop@mail.nih.gov OI Rais-Bahrami, Soroush/0000-0001-9466-9925 FU National Cancer Institute; Center for Interventional Oncology; NIH FX NIH and Philips Healthcare have a cooperative research and development agreement. NIH and Philips Healthcare share intellectual property in the field. This work was supported by the National Cancer Institute, the Center for Interventional Oncology, and the Intramural Research Program of the NIH. This research was made possible through the 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 29 TC 22 Z9 22 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD MAY PY 2015 VL 115 IS 5 BP 772 EP 779 DI 10.1111/bju.12871 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CG4CT UT WOS:000353230500018 PM 25045781 ER PT J AU Yamazaki, F Moller, M Fu, C Clokie, SJ Zykovich, A Coon, SL Klein, DC Rath, MF AF Yamazaki, Fumiyoshi Moller, Morten Fu, Cong Clokie, Samuel J. Zykovich, Artem Coon, Steven L. Klein, David C. Rath, Martin F. TI The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus SO Brain Structure & Function LA English DT Article DE Lhx9; Homeobox gene; Brain development; Pineal gland; Hydrocephalus ID RNA-SEQ; SUBCOMMISSURAL ORGAN; EXPRESSION PATTERNS; S-ANTIGEN; RETINA; RAT; EYE; FOREBRAIN; ADULT; BRAIN AB Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9 (-/-) mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9 (-/-) mutant mice appear normal, severe hydrocephalus develops in about 70 % of the Lhx9 (-/-) mice at 5-8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9 (-/-)mutant mice, the neonatal pineal gland in these animals is hypoplastic. Accordingly, it appears that Lhx9 is essential for early development of the mammalian pineal gland and that this effect is not secondary to hydrocephalus. C1 [Yamazaki, Fumiyoshi; Fu, Cong; Clokie, Samuel J.; Zykovich, Artem; Coon, Steven L.; Klein, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Moller, Morten; Rath, Martin F.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Neurosci & Pharmacol, Copenhagen, Denmark. RP Klein, DC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, Program Dev Endocrinol & Genet, NIH, 49 Convent Dr,Room 6A82, Bethesda, MD 20892 USA. EM kleind@mail.nih.gov OI Clokie, Samuel/0000-0002-0025-3652; Rath, Martin/0000-0002-4047-6324 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health; Lundbeck Foundation [R108-A10301] FX This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health and the Lundbeck Foundation (grant number R108-A10301). We are grateful to Dr. Heiner Westphal's (NICHD) gift of the Lhx9-/- mice and for the support provided by Dr. Yangu Zhao (NICHD) in establishing a colony of Lhx9 mutant mice. We recognize the full value of the willingness of Dr. Joseph D. Dougherty, Washington University, to share unpublished observations. The expertise and dedication of Daniel Abebe as applied to the expansion and management of the mutant Lhx9 colony in our facilities, which was essential to the success of this investigation, is greatly valued. The authors declare no competing financial interests. NR 45 TC 2 Z9 2 U1 0 U2 6 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD MAY PY 2015 VL 220 IS 3 BP 1497 EP 1509 DI 10.1007/s00429-014-0740-x PG 13 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA CG7VX UT WOS:000353515200018 PM 24647753 ER PT J AU Acs, P Bauer, PO Mayer, B Bera, T Macallister, R Mezey, E Pastan, I AF Acs, Peter Bauer, Peter O. Mayer, Balazs Bera, Tapan Macallister, Rhonda Mezey, Eva Pastan, Ira TI A novel form of ciliopathy underlies hyperphagia and obesity in Ankrd26 knockout mice SO Brain Structure & Function LA English DT Article DE Obesity; Neuronal cilia; Leptin receptor; ANKRD26; Melanocortin receptor; Feeding behavior; Paraventricular nucleus; Arcuate nucleus; CRH; Ciliary body proteins ID BARDET-BIEDL-SYNDROME; CORTICOTROPIN-RELEASING HORMONE; MELANOCYTE-STIMULATING HORMONE; PROTEIN-COUPLED-RECEPTORS; FOOD-INTAKE; MELANOCORTIN-4 RECEPTOR; PARAVENTRICULAR NUCLEUS; CILIARY ROOTLET; LEPTIN RECEPTOR; GENE-EXPRESSION AB Human ciliopathies are genetic disorders caused by mutations in genes responsible for the formation and function of primary cilia. Some are associated with hyperphagia and obesity (e.g., Bardet-Biedl Syndrome, Alstrom Syndrome), but the mechanisms underlying these problems are not fully understood. The human gene ANKRD26 is located on 10p12, a locus that is associated with some forms of hereditary obesity. Previously, we reported that disruption of this gene causes hyperphagia, obesity and gigantism in mice. In the present study, we looked for the mechanisms that induce hyperphagia in the Ankrd26-/- mice and found defects in primary cilia in regions of the central nervous system that control appetite and energy homeostasis. C1 [Acs, Peter; Bera, Tapan; Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Bauer, Peter O.] NCI, Neurooncol Branch, NINDS, NIH, Bethesda, MD 20892 USA. [Mayer, Balazs; Mezey, Eva] Natl Inst Dent & Craniofacial Res, Adult Stem Cell Unit, CSDB, NIH, Bethesda, MD 20892 USA. [Macallister, Rhonda] NCI, NIH, Bethesda, MD 20892 USA. RP Mezey, E (reprint author), Natl Inst Dent & Craniofacial Res, Adult Stem Cell Unit, CSDB, NIH, Bethesda, MD 20892 USA. EM mezeye@mail.nih.gov FU Division of Intramural Research program of NCI; NIDCR in the Intramural Research Program, NIH, DHHS FX The authors want to acknowledge the invaluable help of Miklos Palkovits, Harold Gainer and Michael Brownstein for their continuous support and advice as well as help with editing the manuscript. We also thank Prof. Ronald DeKloet (Leiden University) for his expert advice regarding studies on adrenal function. This research was supported by the Division of Intramural Research program of NCI and NIDCR in the Intramural Research Program, NIH, DHHS. We dedicate this work to the memory of Wylie Vale, who discovered CRF and who was an outstanding scientist; a wonderful human being and a good friend. NR 60 TC 4 Z9 4 U1 3 U2 12 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD MAY PY 2015 VL 220 IS 3 BP 1511 EP 1528 DI 10.1007/s00429-014-0741-9 PG 18 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA CG7VX UT WOS:000353515200019 PM 24633808 ER PT J AU Enewold, L Geiger, AM Zujewski, J Harlan, LC AF Enewold, Lindsey Geiger, Ann M. Zujewski, JoAnne Harlan, Linda C. TI Oncotype Dx assay and breast cancer in the United States: usage and concordance with chemotherapy SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Female; Breast cancer; Tumor markers, biological/*genetics; Chemotherapy, adjuvant; SEER ID GENE-EXPRESSION; RECURRENCE; RISK; TAMOXIFEN; UTILITY; WOMEN AB The 21-gene recurrence score (RS) assay (Oncotype DX (TM)) predicts the likelihood of breast cancer recurrence and chemotherapy responsiveness. The aims of this study were to describe temporal trends in assay usage, to investigate factors associated with the receipt of the assay and to determine how the assay is associated with treatment decisions. Random samples of stage I-II female breast cancer patients diagnosed in 2004, 2005 and 2010 as reported to the National Cancer Institute's Surveillance Epidemiology and End Results program were included. Among women diagnosed in 2010 with estrogen receptor positive (ER+), lymph node-negative (LN-) tumors, factors associated with receipt of the assay were identified and the likelihood of chemotherapy by RS was estimated. Assay usage increased over time (ER+/LN-:8.0-27.0 %, p < 0.01; ER+/LN+: 2.0-15.7 %, p = 0.09; ER-: 0.2-1.7 %, p < 0.01) from 2005 to 2010. Receipt of the assay was associated with younger age, lower area income and tumor characteristics. Among women in the low (RS < 18) and high risk (RS > 30) categories, 3.3 and 95.9 % received chemotherapy, respectively. Within the intermediate risk group the receipt of chemotherapy varied: 12.8 % (RS: 18-19), 35.0 % (RS: 20-23) and 84.0 % (RS: 24-30). During the study years, assay usage increased among women for whom the assay is and is not guideline recommended. Factors such as insurance and race/ethnicity do not appear to be associated with the receipt of the assay. The RS, as determined broadly via three categories and within the intermediate risk group, does appear to influence chemotherapy decisions. C1 [Enewold, Lindsey; Geiger, Ann M.; Zujewski, JoAnne; Harlan, Linda C.] NCI, Appl Res Program, Bethesda, MD 20892 USA. RP Enewold, L (reprint author), NCI, Appl Res Program, 9609 Med Ctr Dr,Room 3E506, Bethesda, MD 20892 USA. EM lindsey.enewold@nih.gov FU National Cancer Institute [HHSN261201000024C, HHSN261201000025C, HHSN261201000032C, HHSN261201000027C, HHSN261201000 026C, HHSN261201000140C, HHSN261201000037C, HHSN26120 1000033C, HHSN261201000034C, HHSN261201000035C, HHSN 261201000029C, HHSN261201000031C, HHSN261201000028C, HHSN261201000030C] FX This work was supported by National Cancer Institute contracts: HHSN261201000024C; HHSN261201000025C, HHSN261201000032C, HHSN261201000027C, HHSN261201000 026C, HHSN261201000140C, HHSN261201000037C, HHSN26120 1000033C, HHSN261201000034C, HHSN261201000035C, HHSN 261201000029C, HHSN261201000031C, HHSN261201000028C, and HHSN261201000030C. The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors. This article was produced by employees of the US government as part of their official duties and, as such, is in the public domain in the United States of America. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 31 TC 8 Z9 8 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAY PY 2015 VL 151 IS 1 BP 149 EP 156 DI 10.1007/s10549-015-3366-7 PG 8 WC Oncology SC Oncology GA CG5RU UT WOS:000353352500014 PM 25859924 ER PT J AU Bonano, JS Banks, ML Kolanos, R Sakloth, F Barnier, ML Glennon, RA Cozzi, NV Partilla, JS Baumann, MH Negus, SS AF Bonano, J. S. Banks, M. L. Kolanos, R. Sakloth, F. Barnier, M. L. Glennon, R. A. Cozzi, N. V. Partilla, J. S. Baumann, M. H. Negus, S. S. TI Quantitative structure-activity relationship analysis of the pharmacology of para-substituted methcathinone analogues SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article ID INTRACRANIAL SELF-STIMULATION; BATH SALTS; SYNTHETIC CATHINONES; MONOAMINE TRANSPORTERS; ARRIVE GUIDELINES; ABUSE; DRUGS; MEPHEDRONE; BRAIN; 4-METHYLMETHCATHINONE AB Background and PurposeMethcathinone (MCAT) is a potent monoamine releaser and parent compound to emerging drugs of abuse including mephedrone (4-CH3 MCAT), the para-methyl analogue of MCAT. This study examined quantitative structure-activity relationships (QSAR) for MCAT and six para-substituted MCAT analogues on (a) in vitro potency to promote monoamine release via dopamine and serotonin transporters (DAT and SERT, respectively), and (b) in vivo modulation of intracranial self-stimulation (ICSS), a behavioural procedure used to evaluate abuse potential. Neurochemical and behavioural effects were correlated with steric (E-s), electronic (sigma(p)) and lipophilic ((p)) parameters of the para substituents. Experimental ApproachFor neurochemical studies, drug effects on monoamine release through DAT and SERT were evaluated in rat brain synaptosomes. For behavioural studies, drug effects were tested in male Sprague-Dawley rats implanted with electrodes targeting the medial forebrain bundle and trained to lever-press for electrical brain stimulation. Key ResultsMCAT and all six para-substituted analogues increased monoamine release via DAT and SERT and dose- and time-dependently modulated ICSS. In vitro selectivity for DAT versus SERT correlated with in vivo efficacy to produce abuse-related ICSS facilitation. In addition, the E-s values of the para substituents correlated with both selectivity for DAT versus SERT and magnitude of ICSS facilitation. Conclusions and ImplicationsSelectivity for DAT versus SERTin vitro is a key determinant of abuse-related ICSS facilitation by these MCAT analogues, and steric aspects of the para substituent of the MCAT scaffold (indicated by E-s) are key determinants of this selectivity. C1 [Bonano, J. S.; Banks, M. L.; Negus, S. S.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA USA. [Kolanos, R.; Sakloth, F.; Barnier, M. L.; Glennon, R. A.] Virginia Commonwealth Univ, Dept Med Chem, Richmond, VA 23298 USA. [Cozzi, N. V.] Univ Wisconsin, Dept Cell & Regenerat Biol, Madison, WI USA. [Partilla, J. S.; Baumann, M. H.] NIDA, Designer Drug Res Unit, Intramural Res Program, NIH, Baltimore, MD USA. RP Bonano, JS (reprint author), 410 North 12th St,Smith Bldg Room 760B,POB 980613, Richmond, VA 23298 USA. EM bonanojs@vcu.edu RI Banks, Matthew/K-4429-2014 OI Banks, Matthew/0000-0003-4949-5246 FU National Institutes of Health [F30DA037649, R01DA033930, R21DA017675]; National Institute on Drug Abuse, Intramural Research Programme [DA000523-07] FX This research was supported by the National Institutes of Health grants F30DA037649 (J. S. B.), R01DA033930 (R. A. G. and S. S. N.), R21DA017675 (N. V. C.) and by the National Institute on Drug Abuse, Intramural Research Programme Grant DA000523-07 (M. H. B.). NR 46 TC 10 Z9 10 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1188 EI 1476-5381 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAY PY 2015 VL 172 IS 10 BP 2433 EP 2444 DI 10.1111/bph.13030 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CG6EQ UT WOS:000353389600002 PM 25438806 ER PT J AU Altimari, JM Hockey, SC Boshoff, HI Sajid, A Henderson, LC AF Altimari, Jarrad M. Hockey, Samantha C. Boshoff, Helena I. Sajid, Andaleeb Henderson, Luke C. TI Novel 1,4-Substituted-1,2,3-Triazoles as Antitubercular Agents SO CHEMMEDCHEM LA English DT Article DE antibacterial agents; azides; click chemistry; Mycobacterium tuberculosis; triazoles; tuberculosis ID ANDROGEN RECEPTOR ANTAGONISTS; MYCOBACTERIUM-TUBERCULOSIS; POTENT INHIBITORS; CLICK CHEMISTRY; BIOLOGICAL EVALUATION; TRIAZOLE DERIVATIVES; DRUG DEVELOPMENT; DESIGN; 1,2,3-TRIAZOLES; INHA AB Tuberculosis (TB) remains a pressing unmet medical need, particularly with the emergence of multidrug-resistant and extensively drug-resistant tuberculosis. Here, a series of 1,4-substituted-1,2,3-triazoles have been synthesized and evaluated as potential antitubercular agents. These compounds were assembled via click chemistry in high crude purity and in moderate to high yield. Of the compounds tested, 12 compounds showed promising antitubercular activity with six possessing minimum inhibitory concentration (MIC) values <10gmL(-1), and total selectivity for Mycobacterium tuberculosis (Mtb) growth inhibition. A second set of 21 compounds bearing variations on ringC were synthesized and evaluated. This second library gave an additional six compounds displaying MIC values 10gmL(-1) and total selectivity for Mtb growth inhibition. These compounds serve as an excellent starting point for further development of antitubercular therapies. C1 [Altimari, Jarrad M.; Hockey, Samantha C.; Henderson, Luke C.] Deakin Univ, Inst Frontier Mat, Geelong, Vic 3216, Australia. [Altimari, Jarrad M.; Hockey, Samantha C.; Henderson, Luke C.] Deakin Univ, Strateg Res Ctr Chem & Biotechnol, Geelong, Vic 3216, Australia. [Boshoff, Helena I.; Sajid, Andaleeb] NIAID, TB Res Sect, LCID, NIH, Bethesda, MD 20892 USA. RP Altimari, JM (reprint author), Deakin Univ, Inst Frontier Mat, Waurn Ponds Campus, Geelong, Vic 3216, Australia. EM luke.henderson@deakin.edu.au OI Sajid, Andaleeb/0000-0001-6248-4985; Henderson, Luke/0000-0002-4244-2056 FU Deakin University (Australia) Strategic Research Center for Chemistry and Biotechnology; School of Life and Environmental Sciences; Faculty of Science Engineering and Built Environment; National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH); Australian government FX The authors thank the Deakin University (Australia) Strategic Research Center for Chemistry and Biotechnology, the School of Life and Environmental Sciences and the Faculty of Science Engineering and Built Environment for financial support of this project. This work was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH). J.A. gratefully acknowledges the Australian government for the Australian Postgraduate Award (APA) scholarship. NR 30 TC 3 Z9 3 U1 3 U2 22 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1860-7179 EI 1860-7187 J9 CHEMMEDCHEM JI ChemMedChem PD MAY PY 2015 VL 10 IS 5 BP 787 EP 791 DI 10.1002/cmdc.201500051 PG 5 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CG7HM UT WOS:000353473600002 PM 25788466 ER PT J AU Kotlyar, DS Lewis, JD Beaugerie, L Tierney, A Brensinger, CM Gisbert, JP Loftus, EV Peyrin-Biroulet, L Blonski, WC Van Domselaar, M Chaparro, M Sandilya, S Bewtra, M Beigel, F Biancone, L Lichtenstein, GR AF Kotlyar, David S. Lewis, James D. Beaugerie, Laurent Tierney, Ann Brensinger, Colleen M. Gisbert, Javier P. Loftus, Edward V., Jr. Peyrin-Biroulet, Laurent Blonski, Wojciech C. Van Domselaar, Manuel Chaparro, Maria Sandilya, Sandipani Bewtra, Meenakshi Beigel, Florian Biancone, Livia Lichtenstein, Gary R. TI Risk of Lymphoma in Patients With Inflammatory Bowel Disease Treated With Azathioprine and 6-Mercaptopurine: A Meta-analysis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Cancer Risk; Ulcerative Colitis; Crohn's Disease; Treatment ID NON-HODGKINS-LYMPHOMA; SINGLE-CENTER COHORT; T-CELL LYMPHOMA; RHEUMATOID-ARTHRITIS; ULCERATIVE-COLITIS; CROHNS-DISEASE; CANCER-RISK; TRANSPLANTATION; ASSOCIATION; THIOPURINES AB BACKGROUND & AIMS: Thiopurine therapy for inflammatory bowel disease (IBD) has been associated with increased risk for lymphoma. We estimated the relative risk of lymphoma in patients with IBD exposed to thiopurines and compared relative risk values derived from population-based studies with those from referral center-based studies. We investigated whether active use increased risk compared with past use, and whether sex, age, or duration of use affects risk of lymphoma. METHODS: We searched MEDLINE, EMBASE, and Cochrane databases, as well as conference abstracts and international publications, for the terms "6-MP and lymphoma," "6-mercaptopurine and lymphoma," "thiopurines and lymphoma," "azathioprine and cancer and IBD," "azathioprine and malignancy and IBD," "azathioprine and lymphoma," and "lymphoproliferative and thiopurines." Pooled standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were estimated. The deviance statistic from Poisson models was used to calculate heterogeneity. RESULTS: Eighteen studies (among 4383 citations) met our inclusion criteria. Overall, the SIR for lymphoma was 4.92 (95% CI, 3.10-7.78), ranging from 2.80 (95% CI, 1.82-4.32) in 8 population studies to 9.24 (95% CI, 4.69-18.2) in 10 referral studies. Population studies demonstrated an increased risk among current users (SIR = 5.71; 95% CI, 3.72-10.1) but not former users (SIR = 1.42; 95% CI, 0.86-2.34). Level of risk became significant after 1 year of exposure. Men have a greater risk than women (relative risk = 1.98; P<.05); both sexes were at increased risk for lymphoma (SIR for men = 4.50; 95% CI = 3.71-5.40 and SIR for women = 2.29; 95% CI = 1.69-3.05). Patients younger than 30 years had the highest relative risk (SIR = 6.99; 95% CI, 2.99-16.4); younger men had the highest risk. The absolute risk was highest in patients older than 50 years (1: 354 cases per patient-year, with a relative risk of 4.78). CONCLUSIONS: Compared with studies from referral centers, population-based studies of IBD patients show a lower but significantly increased risk of lymphoma among patients taking thiopurines. The increased risk does not appear to persist after discontinuation of therapy. Patients over 50 have the highest absolute risk of lymphoma per year on thiopurines, while men under 35 may also be a high risk group. More study is needed to precisely understand groups highest at risk. The risks of lymphoma and potential benefits of therapy should be considered for all patients with IBD. C1 [Kotlyar, David S.] NCI, Med Oncol Serv, NIH, Bethesda, MD 20892 USA. [Kotlyar, David S.; Lewis, James D.; Blonski, Wojciech C.; Bewtra, Meenakshi; Lichtenstein, Gary R.] Univ Penn, Perelman Sch Med, Dept Med, Div Gastroenterol, Philadelphia, PA 19174 USA. [Lewis, James D.; Tierney, Ann; Brensinger, Colleen M.; Bewtra, Meenakshi] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19174 USA. [Beaugerie, Laurent] Univ Paris 06, Hop St Antoine, AP HP, Gastroenterol, Paris, France. [Gisbert, Javier P.; Chaparro, Maria] La Princesa Univ Hosp, Inst Invest Sanitaria Princesa IP, Gastroenterol, Madrid, Spain. [Gisbert, Javier P.; Chaparro, Maria] CIBERehd, Madrid, Spain. [Loftus, Edward V., Jr.] Mayo Clin, Dept Med, Div Gastroenterol & Hepatol, Rochester, MN USA. [Peyrin-Biroulet, Laurent] Nancy Univ Hosp, INSERM, Dept Gastroenterol, U954, Nancy, France. [Blonski, Wojciech C.] SUNY Upstate, Dept Med, Binghamton, NY USA. [Blonski, Wojciech C.] Med Univ, Wroclaw, Poland. [Van Domselaar, Manuel] Hosp Ramon & Cajal, Gastroenterol, E-28034 Madrid, Spain. [Sandilya, Sandipani] Montefiore Med Ctr, Dept Med, Div Nephrol, Bronx, NY 10467 USA. [Beigel, Florian] Univ Munich Grosshadern, Dept Med, Munich, Germany. [Biancone, Livia] Univ Roma Tor Vergata, Dept Med, GI Unit, Rome, Italy. RP Lichtenstein, GR (reprint author), Univ Penn, Perelman Sch Med, Perelman Bldg,7-South Room 753,3400 Civ Ctr Blvd, Philadelphia, PA 19174 USA. EM grl@mail.med.upenn.edu RI Loftus, Edward/E-8304-2011; OI Gisbert, Javier Perez/0000-0003-2090-3445 FU Intramural Research Program at the National Institutes of Health - United States Government FX David S. Kotlyar is supported by the Intramural Research Program at the National Institutes of Health, funded by the United States Government. NR 43 TC 40 Z9 40 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAY PY 2015 VL 13 IS 5 BP 847 EP U541 DI 10.1016/j.cgh.2014.05.015 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CG1XN UT WOS:000353069000012 PM 24879926 ER PT J AU Kesarwala, AH Ko, CJ Ning, H Xanthopoulos, E Haglund, KE O'Meara, WP Simone, CB Rengan, R AF Kesarwala, Aparna H. Ko, Christine J. Ning, Holly Xanthopoulos, Eric Haglund, Karl E. O'Meara, William P. Simone, Charles B., II Rengan, Ramesh TI Intensity-Modulated Proton Therapy for Elective Nodal Irradiation and Involved-Field Radiation in the Definitive Treatment of Locally Advanced Non-Small-Cell Lung Cancer: A Dosimetric Study SO CLINICAL LUNG CANCER LA English DT Article DE ENI; IFRT; IMPT; NSCLC; Radiation therapy ID POSITRON-EMISSION-TOMOGRAPHY; DOSE-ESCALATION; PHASE-III; RADIOTHERAPY; TRIAL; TUMOR; CHEMOTHERAPY; CONCURRENT; VOLUME; NSCLC AB In this study we examined the feasibility of intensity-modulated proton therapy for elective nodal irradiation in locally-advanced non-small-cell lung cancer. Proton involved-field and elective nodal irradiation improved target coverage and dosimetry to all evaluated organs at risk compared with photon involved-field radiation therapy, demonstrating potential for enhancement of the therapeutic window. Background: Photon involved-field (IF) radiation therapy (IFRT), the standard for locally advanced (LA) non-small cell lung cancer (NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Because of the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. Patients and Methods: IMPT IFRT plans were generated to the same total dose of 66.6-72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 cobalt Gray equivalent (CGE) to elective nodal planning treatment volumes (PTV) plus 24 CGE to IF-PTVs. Results: Proton IFRT and ENI improved the IF-PTV percentage of volume receiving 95% of the prescribed dose (D95) by 4% (P < .01) compared with photon IFRT. All evaluated dosimetric parameters improved significantly with both proton plans. The lung percentage of volume receiving 20 Gy/CGE (V20) and mean lung dose decreased 18% (P < .01) and 36% (P < .01), respectively, with proton IFRT, and 11% (P = .03) and 26% (P < .01) with ENI. The mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all P < .01). Conclusion: This study demonstrates the feasibility of IMPT for LA-NSCLC ENI. Potential decreased toxicity indicates that IMPT could allow ENI while maintaining a favorable therapeutic ratio compared with photon IFRT. C1 [Kesarwala, Aparna H.; Ning, Holly; Haglund, Karl E.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Ko, Christine J.; O'Meara, William P.] Walter Reed Natl Mil Med Ctr, Dept Radiol, Div Radiat Oncol, Bethesda, MD USA. [Xanthopoulos, Eric; Simone, Charles B., II] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Rengan, Ramesh] Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. RP Kesarwala, AH (reprint author), NCI, Radiat Oncol Branch, NIH, Bldg 10 CRC,Room B2-3500, Bethesda, MD 20892 USA. EM aparna.kesarwala@nih.gov FU Intramural Research Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This research was supported in part by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 46 TC 5 Z9 5 U1 2 U2 4 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1525-7304 EI 1938-0690 J9 CLIN LUNG CANCER JI Clin. Lung Cancer PD MAY PY 2015 VL 16 IS 3 BP 237 EP 244 DI 10.1016/j.cllc.2014.12.001 PG 8 WC Oncology SC Oncology GA CG5RC UT WOS:000353350500010 PM 25604729 ER PT J AU Simon, R Blumenthal, GM Rothenberg, ML Sommer, J Roberts, SA Armstrong, DK LaVange, LM Pazdur, R AF Simon, R. Blumenthal, G. M. Rothenberg, M. L. Sommer, J. Roberts, S. A. Armstrong, D. K. LaVange, L. M. Pazdur, R. TI The Role of Nonrandomized Trials in the Evaluation of Oncology Drugs SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ADMINISTRATION APPROVAL; CLINICAL-TRIALS; END-POINTS; PHASE-II; SURVIVAL; CANCER; THERAPIES AB Although randomized trials provide the most reliable evidence of a drug's safety and efficacy, there are situations where randomized trials are not possible or ethical. In this article we discuss when and how single-arm trials can be used to support full approval of oncology drugs. These include situations in which an unprecedented effect on tumor response is observed in a setting of high unmet medical need, clinical trial patients have been well characterized, enabling a target population to be clearly defined, experience exists in a sufficient number of patients to allow adequate assessment of the risk:benefit relationship, and a proper historical context can be provided for analysis. We also discuss how response rates might be considered predictive of long-term outcomes or clinically meaningful in and of themselves in certain contexts. C1 [Simon, R.] NCI, Bethesda, MD 20892 USA. [Blumenthal, G. M.; LaVange, L. M.] US FDA, Silver Spring, MD USA. [Rothenberg, M. L.; Pazdur, R.] Pfizer Inc, New York, NY USA. [Sommer, J.] Chordoma Fdn, Durham, NC USA. [Roberts, S. A.] Friends Canc Res, Washington, DC 20036 USA. [Armstrong, D. K.] Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. RP Roberts, SA (reprint author), Friends Canc Res, Washington, DC 20036 USA. EM sroberts@focr.org FU American Society of Clinical Oncology; Susan G. Komen for the Cure FX This article was developed as an issue brief for the seventh annual Friends of Cancer Research-Brookings Institution Conference on Clinical Cancer Research, held on November 21, 2014. The authors thank the American Society of Clinical Oncology and Susan G. Komen for the Cure for their generous financial support of this conference. We also thank staff at Friends of Cancer Research and the Brookings Institution for their expertise and logistical support, in particular Marina Kozak at Friends of Cancer Research for thoughtful input on the article. NR 20 TC 11 Z9 11 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAY PY 2015 VL 97 IS 5 BP 502 EP 507 DI 10.1002/cpt.86 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CG4DT UT WOS:000353233900011 PM 25676488 ER PT J AU Kemp, TJ Castro, FA Gao, YT Hildesheim, A Nogueira, L Wang, BS Sun, L Shelton, G Pfeiffer, RM Hsing, AW Pinto, LA Koshiol, J AF Kemp, Troy J. Castro, Felipe A. Gao, Yu-Tang Hildesheim, Allan Nogueira, Leticia Wang, Bing-Sheng Sun, Lu Shelton, Gloriana Pfeiffer, Ruth M. Hsing, Ann W. Pinto, Ligia A. Koshiol, Jill TI Application of multiplex arrays for cytokine and chemokine profiling of bile SO CYTOKINE LA English DT Article DE Bile; Gallstones; Cytokines; Chemokines ID BILIARY-TRACT CANCER; GALLBLADDER CANCER; LIVER; RISK; INFLAMMATION; GALLSTONES; MARKERS; IMMUNE; SERUM; CHOLANGITIS AB Background: Gallbladder disease is highly related to inflammation, but the inflammatory processes are not well understood. Bile provides a direct substrate in assessing the local inflammatory response that develops in the gallbladder. To assess the reproducibility of measuring inflammatory markers in bile, we designed a methods study of 69 multiplexed immune-related markers measured in bile obtained from gallstone patients. Methods: To evaluate assay performance, a total of 18 bile samples were tested twice within the same plate for each analyte, and the 18 bile samples were tested on two different days for each analyte. We used the following performance parameters: detectability, coefficient of variation (CV), intraclass correlation coefficient (ICC), and percent agreement (concordance among replicate measures above and below detection limit). Furthermore, we examined the association of analyte levels with gallstone characteristics such as type, numbers, and size. Results: All but 3 analytes (Stem Cell Factor, SCF; Thrombopoietin, TPO; sIL-1RI) were detectable in bile. 52 of 69 (75.4%) analytes had detectable levels for at least 50% of the subjects tested. The within-plate CVs were <= 25% for 53 of 66 (80.3%) detectable analytes, and across-plate CVs were <= 25% for 32 of 66 (48.5%) detectable analytes. Moreover, 64 of 66 (97.0%) analytes had ICC values of at least 0.8. Lastly, the percent agreement was high between replicates for all of the analytes (median; within plate, 97.2%; across plate, 97.2%). In exploratory analyses, we assessed analyte levels by gallstone characteristics and found that levels for several analytes decreased with increasing size of the largest gallstone per patient. Conclusions: Our data suggest that multiplex assays can be used to reliably measure cytokines and chemokines in bile. In addition, gallstone size was inversely related to the levels of select analytes, which may aid in identifying critical pathways and mechanisms associated with the pathogenesis of gallbladder diseases. (c) 2015 Elsevier Ltd. All rights reserved. C1 [Kemp, Troy J.; Shelton, Gloriana; Pinto, Ligia A.] Leidos Biomed Res Inc, HPV Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Castro, Felipe A.; Hildesheim, Allan; Nogueira, Leticia; Koshiol, Jill] NCI, Infect & Immunoepidemiol Branch, DCEG, NIH, Bethesda, MD 20892 USA. [Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Wang, Bing-Sheng] Fudan Univ, Sch Med, Zhongshan Hosp, Dept Gen Surg, Shanghai 200433, Peoples R China. [Sun, Lu] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Pfeiffer, Ruth M.] NCI, Biostat Branch, DCEG, NIH, Bethesda, MD 20892 USA. [Hsing, Ann W.] Canc Prevent Inst Calif, Fremont, CA USA. [Hsing, Ann W.] Stanford Canc Inst, Palo Alto, CA USA. [Hsing, Ann W.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA. RP Pinto, LA (reprint author), Leidos Biomed Res Inc, HPV Immunol Lab, Frederick Natl Lab Canc Res, Bldg 469,Room 111, Frederick, MD 21702 USA. EM kemptj@mail.nih.gov; felipe.castro@nih.gov; ytgao@vip.sina.com; hilde-sha@exchange.nih.gov; leticia.nogueira@nih.gov; wang.bingsheng@zs-hospital.sh.cn; sunlush@126.com; Glori-ana.Shelton@nih.gov; pfeiffer@mail.nih.gov; Ann.Hsing@cpic.org; pintol@mail.nih.gov; koshiolj@mail.nih.gov RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, USA FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Furthermore, The Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, USA provided funds for the current study. NR 30 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD MAY PY 2015 VL 73 IS 1 BP 84 EP 90 DI 10.1016/j.cyto.2015.01.033 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA CG2AY UT WOS:000353078500013 PM 25743242 ER PT J AU Granzin, M Soltenborn, S Muller, S Kollet, J Berg, M Cerwenka, A Childs, RW Huppert, V AF Granzin, Markus Soltenborn, Stephanie Mueller, Sabine Kollet, Jutta Berg, Maria Cerwenka, Adelheid Childs, Richard W. Huppert, Volker TI Fully automated expansion and activation of clinical-grade natural killer cells for adoptive immunotherapy SO CYTOTHERAPY LA English DT Article DE automation; CliniMACS Prodigy; immunotherapy; natural killer cells; NK cell expansion; NK cell therapy ID GENE-EXPRESSION ANALYSIS; ACUTE MYELOID-LEUKEMIA; EX-VIVO EXPANSION; LARGE-SCALE; NK CELLS; CANCER-PATIENTS; PHASE-II; T-CELLS; THERAPY; TRANSPLANTATION AB Background aims. Ex vivo expansion of natural killer (NK) cells is a strategy to produce large numbers of these effector cells for immunotherapy. However, the transfer of bench-top expansion protocols to clinically applicable methods is challenging for NK cell based therapy because of regulatory aspects and scale-up issues. Therefore, we developed an automated, large-scale NK cell expansion process. Methods. Enriched NK cells were expanded with interleukin-2 and irradiated clinical-grade Epstein-Barr virus transformed lymphoblastoid feeder cells with the use of an automated system in comparison to manual expansion, and the cells were investigated for their functionality, phenotype and gene expression. Results. Automated expansion resulted in a mean 850-fold expansion of NK cells by day 14, Yielding 1.3 (+/- 0.9) x 10(9) activated NK cells. Automatically and manually produced NK cells were comparable in target cell lysis, degranulation and production of interferon-gamma and tumor necrosis factor-alpha and had similar high levels of antibody-dependent cellular cytotoxicity against rituximab-treated leukemic cells. NK cells after automated or manual expansion showed similar gene expression and marker profiles. However, expanded NK cells differed significantly from primary NK cells including upregulation of the functional relevant molecules TRAIL and FasL and NK cell activating receptors NKp30, NKG2D and DNAM-1. Neither automatically nor manually expanded NK cells showed reduced telomere length indicative of a conserved proliferative potential. Conclusions. We established an automated method to expand high numbers of clinical-grade NK cells with properties similar to their manually produced counterparts. This automated process represents a highly efficient tool to standardize NK cell processing for therapeutic applications. C1 [Granzin, Markus; Soltenborn, Stephanie; Mueller, Sabine; Kollet, Jutta; Huppert, Volker] Miltenyi Biotec GmbH, D-51429 Bergisch Gladbach, Germany. [Granzin, Markus; Cerwenka, Adelheid] German Canc Res Ctr, Innate Immun Grp, Heidelberg, Germany. [Berg, Maria; Childs, Richard W.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Granzin, M (reprint author), Miltenyi Biotec GmbH, D-51429 Bergisch Gladbach, Germany. EM markusgr@miltenyibiotec.de; volker@miltenyibiotec.de RI Granzin, Markus/M-9226-2015 OI Granzin, Markus/0000-0002-4774-1469 NR 40 TC 8 Z9 8 U1 2 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1465-3249 EI 1477-2566 J9 CYTOTHERAPY JI Cytotherapy PD MAY PY 2015 VL 17 IS 5 BP 621 EP 632 DI 10.1016/j.jcyt.2015.03.611 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA CG5VQ UT WOS:000353364400011 PM 25881519 ER PT J AU Tseng, WL Guyer, AE Briggs-Gowan, MJ Axelson, D Birmaher, B Egger, HL Helm, J Stowe, Z Towbin, KA Wakschlag, LS Leibenluft, E Brotman, MA AF Tseng, Wan-Ling Guyer, Amanda E. Briggs-Gowan, Margaret J. Axelson, David Birmaher, Boris Egger, Helen L. Helm, Jonathan Stowe, Zachary Towbin, Kenneth A. Wakschlag, Lauren S. Leibenluft, Ellen Brotman, Melissa A. TI BEHAVIOR AND EMOTION MODULATION DEFICITS IN PRESCHOOLERS AT RISK FOR BIPOLAR DISORDER SO DEPRESSION AND ANXIETY LA English DT Article DE children; bipolar disorder; familial risk; irritability; inflexible behavior; diagnostic observation ID MANIC-DEPRESSIVE PARENT; SCHEDULE DB-DOS; DIAGNOSTIC-OBSERVATION; PSYCHIATRIC-DISORDERS; DISRUPTIVE-BEHAVIOR; YOUNG-CHILDREN; DIMENSIONAL PSYCHOPATHOLOGY; CHILDHOOD PSYCHOPATHOLOGY; OBSERVATIONAL ASSESSMENT; FAMILY-HISTORY AB BackgroundBipolar disorder (BD) is highly familial, but studies have yet to examine preschoolers at risk for BD using standardized, developmentally appropriate clinical assessment tools. We used such methods to test whether preschoolers at familial risk for BD have more observed difficulty modulating emotions and behaviors than do low-risk preschoolers. Identification of emotional and behavioral difficulties in at-risk preschoolers is crucial for developing new approaches for early intervention and prevention of BD. MethodsUsing the standardized disruptive behavior diagnostic observation schedule (DB-DOS) protocol for preschoolers, we compared 23 preschoolers (M-age: 4.53 0.73 years; 18 males) with a first-degree relative with BD to 21 preschoolers (M-age: 4.65 0.84 years; 11 males) without a family history of BD. We characterized psychopathology in this sample using the Preschool Aged Psychiatric Assessment and behavioral and emotional problems using the Child Behavior Checklist. ResultsHigh-risk preschoolers demonstrated significantly more intense, pervasive, and clinically concerning problems in anger modulation and behavior dysregulation on the DB-DOS than the low-risk group. High-risk relative to low-risk preschoolers, were also more likely to have maternal-reported anxiety and oppositional defiant disorders and internalizing and externalizing problems. ConclusionsClinically concerning problems in anger modulation and behavior regulation, measured during standardized laboratory observation, differentiate preschoolers at high familial risk for BD from those at low risk. Investigation in a large longitudinal sample is critical for replication and for determining whether these observed behavioral differences can be reliably used as prodromal indicators of mood disorders. (C) 2015 Wiley Periodicals, Inc. C1 [Tseng, Wan-Ling; Towbin, Kenneth A.; Leibenluft, Ellen; Brotman, Melissa A.] NIMH, Emot & Dev Branch, NIH, US Dept HHS, Bethesda, MD USA. [Guyer, Amanda E.] Univ Calif Davis, Dept Human Ecol, Ctr Mind & Brain, Davis, CA 95616 USA. [Briggs-Gowan, Margaret J.] Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06032 USA. [Axelson, David] Nationwide Childrens Hosp, Columbus, OH USA. [Axelson, David] Ohio State Univ, Sch Med, Columbus, OH 43210 USA. [Birmaher, Boris] Univ Pittsburgh, Western Psychiat Inst, Pittsburgh, PA USA. [Egger, Helen L.] Duke Univ, Dept Psychiat, Durham, NC 27706 USA. [Helm, Jonathan] Univ Calif Davis, Ctr Mind & Brain, Davis, CA 95616 USA. [Stowe, Zachary] Univ Arkansas, Dept Psychiat, Fayetteville, AR 72701 USA. [Wakschlag, Lauren S.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. RP Tseng, WL (reprint author), Bldg 15K Room 208,MSC 2670,15K North Dr, Bethesda, MD 20892 USA. EM wan-ling.tseng@nih.gov RI Brotman, Melissa/H-7409-2013; OI Egger, Helen/0000-0001-8447-5350 FU National Institute of Mental Health (NIMH); NARSAD [MH068455, MH60952]; Walden W. and Jean Young Shaw Foundation; Children's Brain Research Foundation FX Contract grant sponsor: National Institute of Mental Health (NIMH); contract grant sponsor: NARSAD Young Investigator Award (to A. E. G.); contract grant number: MH068455 (to L. W., M. B. G.); contract grant number: MH60952 (to B. B.), contract grant sponsor: Walden W. and Jean Young Shaw Foundation (to L. W.); contract grant sponsor: Children's Brain Research Foundation (to L. W.). NR 53 TC 1 Z9 1 U1 2 U2 12 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 MAY PY 2015 VL 32 IS 5 BP 325 EP 334 DI 10.1002/da.22342 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CG6LM UT WOS:000353412400003 PM 25691090 ER PT J AU Deveney, CM Hommer, RE Reeves, E Stringaris, A Hinton, KE Haring, CT Vidal-Ribas, P Towbin, K Brotman, MA Leibenluft, E AF Deveney, Christen M. Hommer, Rebecca E. Reeves, Elizabeth Stringaris, Argyris Hinton, Kendra E. Haring, Catherine T. Vidal-Ribas, Pablo Towbin, Kenneth Brotman, Melissa A. Leibenluft, Ellen TI A PROSPECTIVE STUDY OF SEVERE IRRITABILITY IN YOUTHS: 2-AND 4-YEAR FOLLOW-UP SO DEPRESSION AND ANXIETY LA English DT Article DE irritability; longitudinal; DMDD; severe mood dysregulation ID MOOD DYSREGULATION DISORDER; OF-ONSET DISTRIBUTIONS; LIFETIME PREVALENCE; MENTAL-DISORDERS; ADULT OUTCOMES; ASSOCIATIONS; COMORBIDITY; DEPRESSION; PREDICTORS; CHILDREN AB BackgroundSevere, chronic irritability is receiving increased research attention, and is the cardinal symptom of a new diagnostic category, disruptive mood dysregulation disorder (DMDD). Although data from epidemiological community samples suggest that childhood chronic irritability predicts unipolar depression and anxiety in adulthood, whether these symptoms are stable and cause ongoing clinical impairment is unknown. The present study presents 4-year prospective and longitudinal diagnostic and impairment data on a clinical sample of children selected for symptoms of severe irritability (operationalized as severe mood dysregulation [SMD]). MethodsYouth meeting criteria for SMD (n = 200) were evaluated at baseline using standard diagnostic methods. Two-year (n = 78) and 4-year (n = 46) follow-up diagnostic and clinical impairment ratings collected at 6-month intervals were completed with those youths enrolled in the study for a sufficient time. ResultsAlthough the number of youth meeting strict categorical SMD criteria declined over time (49 and 40% at 2 and 4 years, respectively), many individuals not meeting full criteria continued to display clinically significant irritability symptoms (2 years: 42%; 4 years: 37%). Impairment due to these irritability symptoms remained consistently in the moderate range on the Clinical Global Impressions Scale. ConclusionsBy the 4-year follow-up, only 40% of youths meet strict SMD criteria; however, most continue to display clinically impairing symptoms and significant impairment warranting psychiatric treatment. These findings provide evidence for the course of irritability, with implications for DMDD. Future research with populations meeting DMDD criteria and followed through the ages of high risk for psychiatric diagnoses is necessary. (C) 2015 Wiley Periodicals, Inc. C1 [Deveney, Christen M.] Wellesley Coll, Dept Psychol, Wellesley, MA 02481 USA. [Hommer, Rebecca E.] NIMH, Pediatr & Dev Neurosci Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Reeves, Elizabeth; Towbin, Kenneth; Brotman, Melissa A.; Leibenluft, Ellen] NIMH, Emot & Dev Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Stringaris, Argyris; Hinton, Kendra E.; Haring, Catherine T.; Vidal-Ribas, Pablo] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. RP Deveney, CM (reprint author), Wellesley Coll, Dept Psychol, 106 Cent St, Wellesley, MA 02481 USA. EM cdeveney@wellesley.edu RI Brotman, Melissa/H-7409-2013 FU NIMH [NCT00025935] FX Contract grant sponsor: Intramural Research Program of the NIMH; Contract grant number: NCT00025935. NR 29 TC 6 Z9 6 U1 1 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 MAY PY 2015 VL 32 IS 5 BP 364 EP 372 DI 10.1002/da.22336 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CG6LM UT WOS:000353412400008 PM 25504765 ER PT J AU Mauras, N Mazaika, P Buckingham, B Weinzimer, S White, NH Tsalikian, E Hershey, T Cato, A Cheng, PY Kollman, C Beck, RW Ruedy, K Aye, T Fox, L Arbelaez, AM Wilson, D Tansey, M Tamborlane, W Peng, D Marzelli, M Winer, KK Reiss, AL AF Mauras, Nelly Mazaika, Paul Buckingham, Bruce Weinzimer, Stuart White, Neil H. Tsalikian, Eva Hershey, Tamara Cato, Allison Cheng, Peiyao Kollman, Craig Beck, Roy W. Ruedy, Katrina Aye, Tandy Fox, Larry Arbelaez, Ana Maria Wilson, Darrell Tansey, Michael Tamborlane, William Peng, Daniel Marzelli, Matthew Winer, Karen K. Reiss, Allan L. CA Diabet Res Children Network TI Longitudinal Assessment of Neuroanatomical and Cognitive Differences in Young Children With Type 1 Diabetes: Association With Hyperglycemia SO DIABETES LA English DT Article ID SEVERE HYPOGLYCEMIA; NERVOUS-SYSTEM; DISEASE ONSET; BRAIN VOLUME; MELLITUS; RATS; ADOLESCENTS; YOUTH; LIFE; METAANALYSIS AB Significant regional differences in gray and white matter volume and subtle cognitive differences between young diabetic and nondiabetic children have been observed. Here, we assessed whether these differences change over time and the relation with dysglycemia. Children ages 4 to <10 years with (n = 144) and without (n = 72) type 1 diabetes (T1D) had high-resolution structural MRI and comprehensive neurocognitive tests at baseline and 18 months and continuous glucose monitoring and HbA(1c) performed quarterly for 18 months. There were no differences in cognitive and executive function scores between groups at 18 months. However, children with diabetes had slower total gray and white matter growth than control subjects. Gray matter regions (left precuneus, right temporal, frontal, and parietal lobes and right medial-frontal cortex) showed lesser growth in diabetes, as did white matter areas (splenium of the corpus callosum, bilateral superior-parietal lobe, bilateral anterior forceps, and inferior-frontal fasciculus). These changes were associated with higher cumulative hyperglycemia and glucose variability but not with hypoglycemia. Young children with T1D have significant differences in total and regional gray and white matter growth in brain regions involved in complex sensorimotor processing and cognition compared with age-matched control subjects over 18 months, suggesting that chronic hyperglycemia may be detrimental to the developing brain. C1 [Mauras, Nelly; Fox, Larry] Nemours Childrens Clin, Div Endocrinol Diabet & Metab, Jacksonville, FL 32207 USA. [Mazaika, Paul; Peng, Daniel; Marzelli, Matthew; Reiss, Allan L.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Ctr Interdisciplinary Brain Sci Res, Stanford, CA 94305 USA. [Buckingham, Bruce; Aye, Tandy; Wilson, Darrell; Reiss, Allan L.] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. [Weinzimer, Stuart; Tamborlane, William] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [White, Neil H.; Arbelaez, Ana Maria] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Tsalikian, Eva; Tansey, Michael] Univ Iowa, Pediat Endocrinol, Iowa City, IA USA. [Hershey, Tamara] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Hershey, Tamara] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Hershey, Tamara] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Cato, Allison] Nemours Childrens Clin, Div Neurol, Jacksonville, FL USA. [Cheng, Peiyao; Kollman, Craig; Beck, Roy W.; Ruedy, Katrina] Jaeb Ctr Hlth Res, Tampa, FL USA. [Marzelli, Matthew] Stanford Univ, Sch Med, Dept Bioengn, Stanford, CA 94305 USA. [Winer, Karen K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Reiss, Allan L.] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA. RP Mauras, N (reprint author), Nemours Childrens Clin, Div Endocrinol Diabet & Metab, Jacksonville, FL 32207 USA. EM nmauras@nemours.org FU National Institutes of Health (NIH) [DIRECNET U01-HD-41890, HD-41906, HD-41908, HD-41915, HD-41918, HD-56526, 1R01-HD-078463, UL1-RR-024992] FX This research was supported by funding from the National Institutes of Health (NIH) (DIRECNET U01-HD-41890, HD-41906, HD-41908, HD-41915, HD-41918, and HD-56526), 1R01-HD-078463, and UL1-RR-024992. NR 61 TC 17 Z9 19 U1 1 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD MAY PY 2015 VL 64 IS 5 BP 1770 EP 1779 DI 10.2337/db14-1445 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG6RX UT WOS:000353431200032 PM 25488901 ER PT J AU Torn, C Hadley, D Lee, HS Hagopian, W Lernmark, A Simell, O Rewers, M Ziegler, A Schatz, D Akolkar, B Onengut-Gumuscu, S Chen, WM Toppari, J Mykkanen, J Ilonen, J Rich, SS She, JX Steck, AK Krischer, J AF Torn, Carina Hadley, David Lee, Hye-Seung Hagopian, William Lernmark, Ake Simell, Olli Rewers, Marian Ziegler, Anette Schatz, Desmond Akolkar, Beena Onengut-Gumuscu, Suna Chen, Wei-Min Toppari, Jorma Mykkanen, Juha Ilonen, Jorma Rich, Stephen S. She, Jin-Xiong Steck, Andrea K. Krischer, Jeffrey CA TEDDY Study Grp TI Role of Type 1 Diabetes-Associated SNPs on Risk of Autoantibody Positivity in the TEDDY Study SO DIABETES LA English DT Article ID TYROSINE-PHOSPHATASE PTPN22; ANTIBODY STANDARDIZATION PROGRAM; GLUTAMIC-ACID DECARBOXYLASE; GENOME-WIDE ASSOCIATION; ISLET AUTOIMMUNITY; POPULATION; GENE; POLYMORPHISM; ASSAYS; LOCUS AB The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows 8,677 children enrolled from birth who carry HLA-susceptibility genotypes for development of islet autoantibodies (IA) and type 1 diabetes (T1D). During the median follow-up time of 57 months, 350 children developed at least one persistent IA (GAD antibody, IA-2A, or micro insulin autoantibodies) and 84 of them progressed to T1D. We genotyped 5,164 Caucasian children for 41 non-HLA single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with T1D in the genome-wide association scan meta-analysis conducted by the Type 1 Diabetes Genetics Consortium. In TEDDY participants carrying high-risk HLA genotypes, eight SNPs achieved significant association to development of IA using time-to-event analysis (P < 0.05), whereof four were significant after adjustment for multiple testing (P < 0.0012): rs2476601 in PTPN22 (hazard ratio [HR] 1.54 [95% CI 1.27-1.88]), rs2292239 in ERBB3 (HR 1.33 [95% CI 1.14-1.55]), rs3184504 in SH2B3 (HR 1.38 [95% CI 1.19-1.6]), and rs1004446 in INS (HR 0.77 [0.66-0.90]). These SNPs were also significantly associated with T1D in particular: rs2476601 (HR 2.42 [95% CI 1.70-3.44]). Although genes in the HLA region remain the most important genetic risk factors for T1D, other non-HLA genetic factors contribute to IA, a first step in the pathogenesis of T1D, and the progression of the disease. C1 [Torn, Carina; Lernmark, Ake] Lund Univ, CRC, Dept Clin Sci, Malmo, Sweden. [Hadley, David; Lee, Hye-Seung; Krischer, Jeffrey] Univ S Florida, Dept Pediat, Pediat Epidemiol Ctr, Tampa, FL 33620 USA. [Hadley, David] St Georges Univ London, Div Populat Hlth Sci & Educ, London, England. [Hagopian, William] Pacific Northwest Diabet Res Inst, Seattle, WA USA. [Simell, Olli; Toppari, Jorma; Mykkanen, Juha] Univ Turku, Dept Pediat, Turku, Finland. [Rewers, Marian; Steck, Andrea K.] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA. [Ziegler, Anette] Diabet Res Inst, Dept Pediat, Munich, Germany. [Schatz, Desmond] Univ Florida, Dept Pediat, Gainesville, FL USA. [Akolkar, Beena] NIDDK, NIH, Bethesda, MD 20892 USA. [Onengut-Gumuscu, Suna; Chen, Wei-Min; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Ilonen, Jorma] Univ Turku, Immunogenet Lab, Turku, Finland. [Ilonen, Jorma] Univ Eastern Finland, Dept Clin Microbiol, Kuopio, Finland. [She, Jin-Xiong] Georgia Regents Univ, Ctr Biotechnol & Genom Med, Augusta, GA USA. RP Torn, C (reprint author), Lund Univ, CRC, Dept Clin Sci, Malmo, Sweden. EM carina.torn@med.lu.se RI Ziegler, Anette-Gabriele/M-4614-2014; Bonifacio, Ezio/E-7700-2010; Mykkanen, Juha/Q-1663-2015 OI Ziegler, Anette-Gabriele/0000-0002-6290-5548; Bonifacio, Ezio/0000-0002-8704-4713; Mykkanen, Juha/0000-0001-9898-2660 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, HHSN267200700014C]; National Institute of Allergy and Infectious Diseases; National Institute of Child Health and Human Development; National Institute of Environmental Health Sciences; JDRF; Centers for Disease Control and Prevention; National Institutes of Health/National Center for Advancing Translational Sciences Clinical and Translational Science Awards [UL1 TR000064, UL1 TR001082]; Royal Physiographic Society in Lund, Sweden FX This work was funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, and UC4 DK95300 and contract number HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the National Institute of Child Health and Human Development, the National Institute of Environmental Health Sciences, JDRF, and the Centers for Disease Control and Prevention. This work was supported in part by the National Institutes of Health/National Center for Advancing Translational Sciences Clinical and Translational Science Awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR001082). The Royal Physiographic Society in Lund, Sweden, contributed with a travel grant to C.T. for participation in the 2013 Immunology of Diabetes Society Meeting. NR 40 TC 15 Z9 15 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD MAY PY 2015 VL 64 IS 5 BP 1818 EP 1829 DI 10.2337/db14-1497 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG6RX UT WOS:000353431200037 PM 25422107 ER PT J AU Steck, AK Vehik, K Bonifacio, E Lernmark, A Ziegler, AG Hagopian, WA She, JX Simell, O Akolkar, B Krischer, J Schatz, D Rewers, MJ AF Steck, Andrea K. Vehik, Kendra Bonifacio, Ezio Lernmark, Ake Ziegler, Anette-G. Hagopian, William A. She, JinXiong Simell, Olli Akolkar, Beena Krischer, Jeffrey Schatz, Desmond Rewers, Marian J. CA TEDDY Study Grp TI Predictors of Progression From the Appearance of Islet Autoantibodies to Early Childhood Diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY) SO DIABETES CARE LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; GENERAL-POPULATION; PREVENTION TRIAL-TYPE-1; RISK SCORE; TYPE-1; CHILDREN; INSULIN; AUTOIMMUNITY; INDIVIDUALS; ASSOCIATION AB OBJECTIVEWhile it is known that there is progression to diabetes in <10 years in 70% of children with two or more islet autoantibodies, predictors of the progression to diabetes are only partially defined.RESEARCH DESIGN AND METHODSThe Environmental Determinants of Diabetes in the Young (TEDDY) study has observed 8,503 children who were at increased genetic risk for autoimmune diabetes. Insulin autoantibodies (IAAs), GAD65 autoantibodies (GADAs), and insulinoma-associated protein 2 autoantibodies (IA-2As) were measured every 3 months until 4 years of age and every 6 months thereafter; if results were positive, the autoantibodies were measured every 3 months.RESULTSLife table analysis revealed that the cumulative incidence of diabetes by 5 years since the appearance of the first autoantibody differed significantly by the number of positive autoantibodies (47%, 36%, and 11%, respectively, in those with three autoantibodies, two autoantibodies, and one autoantibody, P < 0.001). In time-varying survival models adjusted for first-degree relative status, number of autoantibodies, age at first persistent confirmed autoantibodies, and HLA genotypes, higher mean IAA and IA-2A levels were associated with an increased risk of type 1 diabetes in children who were persistently autoantibody positive (IAAs: hazard ratio [HR] 8.1 [95% CI 4.6-14.2]; IA-2A: HR 7.4 [95% CI 4.3-12.6]; P < 0.0001]). The mean GADA level did not significantly affect the risk of diabetes.CONCLUSIONSIn the TEDDY study, children who have progressed to diabetes usually expressed two or more autoantibodies. Higher IAA and IA-2A levels, but not GADA levels, increased the risk of diabetes in those children who were persistently autoantibody positive. C1 [Steck, Andrea K.; Rewers, Marian J.] Univ Colorado, Sch Med, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA. [Vehik, Kendra; Krischer, Jeffrey] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA. [Bonifacio, Ezio] Tech Univ Dresden, D-01062 Dresden, Germany. [Lernmark, Ake] Lund Univ, Skane Univ Hosp, Clin Res Ctr, Malmo, Sweden. [Ziegler, Anette-G.] Helmholtz Zentrum Munchen, Diabet Res Inst, Neuherberg, Germany. [Ziegler, Anette-G.] Tech Univ Munich, Klinikum Rechts Isar, D-80290 Munich, Germany. [Ziegler, Anette-G.] Forschergrp Diabet eV, Neuherberg, Germany. [Hagopian, William A.] Pacific Northwest Diabet Res Inst, Seattle, WA USA. [She, JinXiong] Georgia Regents Univ, Med Coll Georgia, Augusta, GA USA. [Simell, Olli] Univ Turku, Dept Pediat, Turku, Finland. [Akolkar, Beena] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. [Schatz, Desmond] Univ Florida, Gainesville, FL USA. RP Steck, AK (reprint author), Univ Colorado, Sch Med, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA. EM andrea.steck@ucdenver.edu RI Ziegler, Anette-Gabriele/M-4614-2014; Bonifacio, Ezio/E-7700-2010 OI Ziegler, Anette-Gabriele/0000-0002-6290-5548; Bonifacio, Ezio/0000-0002-8704-4713 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01-DK-63829, U01-DK-63861, U01-DK-63821, U01-DK-63865, U01-DK-63863, U01-DK-63836, U01-DK-63790, UC4-DK-63829, UC4-DK-63861, UC4-DK-63821, UC4-DK-63865, UC4-DK-63863, UC4-DK-63836, UC4-DK95300, HHSN267200700014C]; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Environmental Health Sciences; JDRF; Centers for Disease Control and Prevention; National Institutes of Health/National Center for Advancing Translational Sciences Clinical and Translational Science Awards [UL1-TR-000064, UL1-TR-001082] FX The TEDDY Study Group is funded by grants U01-DK-63829, U01-DK-63861, U01-DK-63821, U01-DK-63865, U01-DK-63863, U01-DK-63836, U01-DK-63790, UC4-DK-63829, UC4-DK-63861, UC4-DK-63821, UC4-DK-63865, UC4-DK-63863, UC4-DK-63836, and UC4-DK95300 and by Contract no. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, JDRF, and Centers for Disease Control and Prevention. This work was supported in part by the National Institutes of Health/National Center for Advancing Translational Sciences Clinical and Translational Science Awards to the University of Florida (UL1-TR-000064) and the University of Colorado (UL1-TR-001082). NR 38 TC 21 Z9 22 U1 0 U2 2 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 MAY PY 2015 VL 38 IS 5 BP 808 EP 813 DI 10.2337/dc14-2426 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CG7SP UT WOS:000353505600020 PM 25665818 ER PT J AU Krischer, JP Lynch, KF Schatz, DA Ilonen, J Lernmark, A Hagopian, WA Rewers, MJ She, JX Simell, OG Toppari, J Ziegler, AG Akolkar, B Bonifacio, E AF Krischer, Jeffrey P. Lynch, Kristian F. Schatz, Desmond A. Ilonen, Jorma Lernmark, Ake Hagopian, William A. Rewers, Marian J. She, Jin-Xiong Simell, Olli G. Toppari, Jorma Ziegler, Anette-G. Akolkar, Beena Bonifacio, Ezio CA TEDDY Study Grp TI The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study SO DIABETOLOGIA LA English DT Article DE Autoimmunity; Diabetes in young children; HLA-DR-DQ genotypes; Incidence; Islet autoantibodies; Type 1 diabetes ID ISLET AUTOANTIBODIES; CLASSIFICATION; ANTIBODIES; ANTIGEN-2; AGE AB Aims/hypothesis Islet autoantibodies, in addition to elevated blood glucose, define type 1 diabetes. These autoantibodies are detectable for a variable period of time before diabetes onset. Thus, the occurrence of islet autoantibodies is associated with the beginning of the disease process. The age at, and order in, which autoantibodies appear may be associated with different genetic backgrounds or environmental exposures, or both. Methods Infants with HLA-DR high-risk genotypes (DR3/4, DR4/4, DR4/8 and DR3/3) were enrolled and prospectively followed with standardised autoantibody assessments quarterly throughout the first 4 years of life and then semi-annually thereafter. Results Autoantibodies appeared in 549/8,503 (6.5%) children during 34,091 person-years of follow-up. Autoantibodies at 3 (0.1%) and 6 (0.2%) months of age were rare. Of the 549, 43.7% had islet autoantibodies to insulin (IAA) only, 37.7% had glutamic acid decarboxylase autoantibodies (GADA) only, 13.8% had both GADA and IAA only, 1.6% had insulinoma antigen-2 only and 3.1% had other combinations. The incidence of IAA only peaked within the first year of life and declined over the following 5 years, but GADA only increased until the second year and remained relatively constant. GADA only were more common than IAA only in HLA-DR3/3 children but less common in HLA-DR4/8 children. Conclusions/interpretation Islet autoantibodies can occur very early in life and the order of appearance was related to HLA-DR-DQ genotype. C1 [Krischer, Jeffrey P.; Lynch, Kristian F.] Univ S Florida, Dept Pediat, Morsani Coll Med, Tampa, FL 33612 USA. [Schatz, Desmond A.] Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA. [Ilonen, Jorma] Univ Eastern Finland, Dept Clin Microbiol, Kuopio, Finland. [Ilonen, Jorma] Univ Turku, Immunogenet Lab, Turku, Finland. [Lernmark, Ake] Lund Univ, Skane Univ Hosp SUS, Dept Clin Sci, CRC, Malmo, Sweden. [Hagopian, William A.] Pacific NW Diabet Res Inst, Seattle, WA USA. [Rewers, Marian J.] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA. [She, Jin-Xiong] Georgia Regents Univ, Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA USA. [Simell, Olli G.; Toppari, Jorma] Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland. [Toppari, Jorma] Univ Turku, Dept Physiol, Turku, Finland. [Ziegler, Anette-G.] Helmholtz Zentrum Munchen, Diabet Res Inst, Neuherberg, Germany. [Ziegler, Anette-G.] Tech Univ Munich, Klinikum Rechts Isar, D-80290 Munich, Germany. [Ziegler, Anette-G.] Helmholtz Zentrum Munchen, Forschergrp Diabet eV, Neuherberg, Germany. [Akolkar, Beena] NIDDK, Bethesda, MD 20892 USA. [Bonifacio, Ezio] Tech Univ Dresden, Ctr Regenerat Therapies Dresden, Dresden, Germany. RP Krischer, JP (reprint author), Univ S Florida, Dept Pediat, Morsani Coll Med, 3650 Spectrum Blvd,Suite 100, Tampa, FL 33612 USA. EM jeffrey.krischer@epi.usf.edu RI Ziegler, Anette-Gabriele/M-4614-2014; Bonifacio, Ezio/E-7700-2010 OI Ziegler, Anette-Gabriele/0000-0002-6290-5548; Bonifacio, Ezio/0000-0002-8704-4713 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, HHSN267200700014C]; National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Child Health and Human Development (NICHD); National Institute of Environmental Health Sciences (NIEHS); Juvenile Diabetes Research Foundation (JDRF); Centers for Disease Control and Prevention (CDC); NIH/NCATS Clinical and Translational Science [UL1 TR000064]; University of Colorado [UL1 TR001082] FX This work was funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, and UC4 DK95300 and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Juvenile Diabetes Research Foundation (JDRF), and Centers for Disease Control and Prevention (CDC). This work supported in part by the NIH/NCATS Clinical and Translational Science Awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR001082). NR 18 TC 40 Z9 41 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD MAY PY 2015 VL 58 IS 5 BP 980 EP 987 DI 10.1007/s00125-015-3514-y PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CF6CL UT WOS:000352644200014 PM 25660258 ER PT J AU Raghavan, S Porneala, B McKeown, N Fox, CS Dupuis, J Meigs, JB AF Raghavan, Sridharan Porneala, Bianca McKeown, Nicola Fox, Caroline S. Dupuis, Josee Meigs, James B. TI Metabolic factors and genetic risk mediate familial type 2 diabetes risk in the Framingham Heart Study SO DIABETOLOGIA LA English DT Article DE Diet; Family history; Genetic risk; Metabolic syndrome; Physical activity; Type 2 diabetes ID INSULIN-SECRETION; LIFE-STYLE; GLUCOSE-TOLERANCE; PHYSICAL-ACTIVITY; YOUNG ADULTHOOD; GLYCEMIC TRAITS; MELLITUS; ASSOCIATION; PARENTS; HERITABILITY AB Aims/hypothesis Type 2 diabetes mellitus in parents is a strong determinant of diabetes risk in their offspring. We hypothesise that offspring diabetes risk associated with parental diabetes is mediated by metabolic risk factors. Methods We studied initially non-diabetic participants of the Framingham Offspring Study. Metabolic risk was estimated using beta cell corrected insulin response (CIR), HOMA-IR or a count of metabolic syndrome components (metabolic syndrome score [MSS]). Dietary risk and physical activity were estimated using questionnaire responses. Genetic risk score (GRS) was estimated as the count of 62 type 2 diabetes risk alleles. The outcome of incident diabetes in offspring was examined across levels of parental diabetes exposure, accounting for sibling correlation and adjusting for age, sex and putative mediators. The proportion mediated was estimated by comparing regression coefficients for parental diabetes with (beta (adj)) and without (beta (unadj)) adjustments for CIR, HOMA-IR, MSS and GRS (percentage mediated = 1 - beta(adj)/beta(unadj)). Results Metabolic factors mediated 11% of offspring diabetes risk associated with parental diabetes, corresponding to a reduction in OR per diabetic parent from 2.13 to 1.96. GRS mediated 9% of risk, corresponding to a reduction in OR per diabetic parent from 2.13 to 1.99. Conclusions/interpretation Metabolic risk factors partially mediated offspring type 2 diabetes risk conferred by parental diabetes to a similar magnitude as genetic risk. However, a substantial proportion of offspring diabetes risk associated with parental diabetes remains unexplained by metabolic factors, genetic risk, diet and physical activity, suggesting that important familial influences on diabetes risk remain undiscovered. C1 [Raghavan, Sridharan; Porneala, Bianca; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. [Raghavan, Sridharan; Porneala, Bianca; Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McKeown, Nicola] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Epidemiol Program, Boston, MA 02111 USA. [Fox, Caroline S.] NHLBI, Lab Metab & Populat Hlth, Framingham, MA USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Meigs, JB (reprint author), Harvard Univ, Sch Med, Dept Med, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org FU National Institutes of Health National Research Service [T32HP10251]; Ryoichi Sasakawa Fellowship Fund; NIH [RO1DK78616]; National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix for genotyping services [N02-HL-6-4278]; USDA [1950-51530-011-00D]; [K24 DK080140] FX SR is supported by National Institutes of Health National Research Service Award T32HP10251 and the Ryoichi Sasakawa Fellowship Fund. JBM and JD are supported by NIH RO1DK78616, and JBM is also supported by K24 DK080140. We gratefully acknowledge the FHS study participants and staff for their contributions. This work was partially supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix for genotyping services (Contract No. N02-HL-6-4278). NM is supported by USDA agreement number 1950-51530-011-00D. NR 32 TC 1 Z9 1 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD MAY PY 2015 VL 58 IS 5 BP 988 EP 996 DI 10.1007/s00125-015-3498-7 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CF6CL UT WOS:000352644200015 PM 25619168 ER PT J AU Farooq, PD Urrunaga, NH Tang, DM von Rosenvinge, EC AF Farooq, Priya D. Urrunaga, Nathalie H. Tang, Derek M. von Rosenvinge, Erik C. TI Pseudomembranous colitis SO DM DISEASE-A-MONTH LA English DT Article ID CLOSTRIDIUM-DIFFICILE INFECTION; GASTROINTESTINAL CYTOMEGALOVIRUS-INFECTION; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; YERSINIA-ENTEROCOLITICA INFECTIONS; FECAL MICROBIOTA TRANSPLANTATION; RESISTANT STAPHYLOCOCCUS-AUREUS; OF-THE-LITERATURE; ISCHEMIC COLITIS; COLLAGENOUS-COLITIS; STRONGYLOIDES-STERCORALIS C1 [Farooq, Priya D.] Univ Maryland, Med Ctr, Dept Med, Div Gastroenterol & Hepatol, Baltimore, MD 21201 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Vet Affairs Maryland Hlth Ctr Syst, Vet Affairs, Baltimore, MD USA. RP Farooq, PD (reprint author), Univ Maryland, Med Ctr, Dept Med, Div Gastroenterol & Hepatol, Baltimore, MD 21201 USA. FU National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) [5 T32 DK067872-07]; Intramural Research Program of the NIDDK at NIH FX Nathalie H. Urrunaga, MD, MS was supported by Grant no. 5 T32 DK067872-07 from the National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Disease (NIDDK). This document was also supported by the Intramural Research Program of the NIDDK at NIH. NR 182 TC 2 Z9 3 U1 1 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0011-5029 EI 1557-8194 J9 DM-DIS MON JI DM-Dis.-a-Mon. PD MAY PY 2015 VL 61 IS 5 BP 181 EP 206 DI 10.1016/j.disamonth.2015.01.006 PG 26 WC Medicine, General & Internal SC General & Internal Medicine GA CG5DD UT WOS:000353310400002 PM 25769243 ER PT J AU McMahen, RL Strynar, MJ Dagnino, S Herr, DW Moser, VC Garantziotis, S Andersen, EM Freeborn, DL McMillan, L Lindstrom, AB AF McMahen, Rebecca L. Strynar, Mark J. Dagnino, Sonia Herr, David W. Moser, Virginia C. Garantziotis, Stavros Andersen, Erik M. Freeborn, Danielle L. McMillan, Larry Lindstrom, Andrew B. TI Identification of fipronil metabolites by time-of-flight mass spectrometry for application in a human exposure study SO ENVIRONMENT INTERNATIONAL LA English DT Article DE Fipronil; LC/TOF; Biomarker; Human exposure; Metabolism ID HETEROCYCLIC AMINES; ENVIRONMENTAL FATE; FOOD; INSECTICIDE; CYTOCHROME-P450; CHEMISTRY; FLUORINE; SULFONE; INDOOR AB Fipronil is a phenylpyrazole insecticide commonly used in residential and agricultural applications. To understand more about the potential risks for human exposure associated with fipronil, urine and serum from dosed Long Evans adult rats (5 and 10 mg/kg bw) were analyzed to identify metabolites as potential biomarkers for use in human biomonitoring studies. Urine from treated rats was found to contain seven unique metabolites, two of which had not been previously reported-M4 and M7 which were putatively identified as a nitroso compound and an imine, respectively. Fipronil sulfone was confirmed to be the primary metabolite in rat serum. The fipronil metabolites identified in the respective matrices were then evaluated in matched human urine (n = 84) and serum (n = 96) samples from volunteers with no known pesticide exposures. Although no fipronil or metabolites were detected in human urine, fipronil sulfone was present in the serum of approximately 25% of the individuals at concentrations ranging from 0.1 to 4 ng/mL These results indicate that many fipronil metabolites are produced following exposures in rats and that fipronil sulfone is a useful biomarker in human serum. Furthermore, human exposure to fipronil may occur regularly and require more extensive characterization. Published by Elsevier Ltd. C1 [McMahen, Rebecca L.; Strynar, Mark J.; Dagnino, Sonia; Andersen, Erik M.; Lindstrom, Andrew B.] US EPA, Natl Exposure Res Lab, Res Triangle Pk, NC 27711 USA. [Herr, David W.; Moser, Virginia C.; Freeborn, Danielle L.] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. [Garantziotis, Stavros] NIEHS, Res Triangle Pk, NC 27709 USA. [McMillan, Larry] US EPA, Natl Caucus & Ctr Black Aged Employee, Natl Exposure Res Lab, Res Triangle Pk, NC 27711 USA. RP Strynar, MJ (reprint author), 109 TW Alexander Dr, Durham, NC 27705 USA. EM strynar.mark@epa.gov RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU National Exposure Research Laboratory; U.S. Department of Energy; U.S. Environmental Protection Agency FX This research was supported by an appointment to the Research Participation Program at the National Exposure Research Laboratory administered by the Oak Ridge Institute for Science Education through an interagency agreement between the U.S. Department of Energy and the U.S. Environmental Protection Agency. We thank Agilent Technologies for providing us with the LC/TOF mass spectrometer that was used to investigate metabolic products. We also thank Michael Hays of the US EPA who kindly allowed the use of his LC/Q-TOF mass spectrometer for further structure elucidation, Benny Pyke of Arizona State University for discussions on detection of fipronil in human urine, and Matthew Stiegel, Jon Sobus, and Peter Egeghy for help with data analysis. NR 41 TC 6 Z9 6 U1 2 U2 30 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0160-4120 EI 1873-6750 J9 ENVIRON INT JI Environ. Int. PD MAY PY 2015 VL 78 BP 16 EP 23 DI 10.1016/j.envint.2015.01.016 PG 8 WC Environmental Sciences SC Environmental Sciences & Ecology GA CG2GH UT WOS:000353092400003 PM 25687022 ER PT J AU Kengyel, A Becsi, B Konya, Z Sellers, JR Erdodi, F Nyitrai, M AF Kengyel, Andras Becsi, Balint Konya, Zoltan Sellers, James R. Erdodi, Ferenc Nyitrai, Miklos TI Ankyrin domain of myosin 16 influences motor function and decreases protein phosphatase catalytic activity SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Article DE Myosin; Protein phosphatase-1 (PP1); Actin; ATPases; Phosphorylation ID SUBSTRATE-SPECIFICITY; KINETIC MECHANISM; BINDING; MUSCLE; LOCALIZATION; SUBUNIT; REGIONS; DEFINES; FAMILY; CELLS AB The unconventional myosin 16 (Myo16), which may have a role in regulation of cell cycle and cell proliferation, can be found in both the nucleus and the cytoplasm. It has a unique, eight ankyrin repeat containing pre-motor domain, the so-called ankyrin domain (My16Ank). Ankyrin repeats are present in several other proteins, e.g., in the regulatory subunit (MYPT1) of the myosin phosphatase holoenzyme, which binds to the protein phosphatase-1 catalytic subunit (PP1c). My16Ank shows sequence similarity to MYPT1. In this work, the interactions of recombinant and isolated My16Ank were examined in vitro. To test the effects of My16Ank on myosin motor function, we used skeletal muscle myosin or nonmuscle myosin 2B. The results showed that My16Ank bound to skeletal muscle myosin (K (D) a parts per thousand 2.4 A mu M) and the actin-activated ATPase activity of heavy meromyosin (HMM) was increased in the presence of My16Ank, suggesting that the ankyrin domain can modulate myosin motor activity. My16Ank showed no direct interaction with either globular or filamentous actin. We found, using a surface plasmon resonance-based binding technique, that My16Ank bound to PP1c alpha (K (D) a parts per thousand 540 nM) and also to PP1c delta (K (D) a parts per thousand 600 nM) and decreased its phosphatase activity towards the phosphorylated myosin regulatory light chain. Our results suggest that one function of the ankyrin domain is probably to regulate the function of Myo16. It may influence the motor activity, and in complex with the PP1c isoforms, it can play an important role in the targeted dephosphorylation of certain, as yet unidentified, intracellular proteins. C1 [Kengyel, Andras; Nyitrai, Miklos] Univ Pecs, Sch Med, Dept Biophys, H-7624 Pecs, Hungary. [Kengyel, Andras; Nyitrai, Miklos] Janos Szentagothai Res Ctr, Pecs, Hungary. [Becsi, Balint; Konya, Zoltan; Erdodi, Ferenc] Univ Debrecen, Dept Med Chem, Debrecen, Hungary. [Becsi, Balint; Erdodi, Ferenc] Univ Debrecen, MTA DE Cell Biol & Signaling Res Grp, Fac Med, Debrecen, Hungary. [Sellers, James R.] NHLBI, NIH, Bethesda, MD 20892 USA. [Nyitrai, Miklos] MTA PTE Nucl Mitochondrial Interact Res Grp, Pecs, Hungary. RP Nyitrai, M (reprint author), Univ Pecs, Sch Med, Dept Biophys, Szigeti Str 12, H-7624 Pecs, Hungary. EM miklos.nyitrai@aok.pte.hu FU Hungarian Scientific Research Fund (OTKA) [NN 107776, K112794, K109249]; European Union [TAMOP 4.2.4. A/2-11-1-2012-0001]; State of Hungary; European Social Fund FX This work was supported by grants from the Hungarian Scientific Research Fund (OTKA grants NN 107776 and K112794 to M.N. and K109249 to F.E.) and by the "TAMOP 4.2.4. A/2-11-1-2012-0001 National Excellence Program" supported by the European Union and the State of Hungary, co-financed by the European Social Fund to Z.K. and B.B. The authors thank Attila Nagy for preparing and providing NMIIB HMM. NR 39 TC 0 Z9 0 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7571 EI 1432-1017 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD MAY PY 2015 VL 44 IS 4 BP 207 EP 218 DI 10.1007/s00249-015-1015-z PG 12 WC Biophysics SC Biophysics GA CF9AE UT WOS:000352853000002 PM 25775934 ER PT J AU Oh, SK Baek, JI Weigand, KM Venselaar, H Swarts, HGP Park, SH Raza, MH Jung, DJ Choi, SY Lee, SH Friedrich, T Vriend, G Koenderink, JB Kim, UK Lee, KY AF Oh, Se-Kyung Baek, Jeong-In Weigand, Karl M. Venselaar, Hanka Swarts, Herman G. P. Park, Seong-Hyun Raza, Muhammad Hashim Jung, Da Jung Choi, Soo-Young Lee, Sang-Heun Friedrich, Thomas Vriend, Gert Koenderink, Jan B. Kim, Un-Kyung Lee, Kyu-Yup TI A missense variant of the ATP1A2 gene is associated with a novel phenotype of progressive sensorineural hearing loss associated with migraine SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FAMILIAL HEMIPLEGIC MIGRAINE; CATION-BINDING POCKET; GASTRIC H,K-ATPASE; NA+/K+-ATPASE; K+-ATPASE; NA,K-ATPASE; MUTATIONS; NA+,K+-ATPASE; OUABAIN; PUMP AB Hereditary sensorineural hearing loss is an extremely clinical and genetic heterogeneous disorder in humans. Especially, syndromic hearing loss is subdivided by combinations of various phenotypes, and each subtype is related to different genes. We present a new form of progressive hearing loss with migraine found to be associated with a variant in the ATP1A2 gene. The ATP1A2 gene has been reported as the major genetic cause of familial migraine by several previous studies. A Korean family presenting progressive hearing loss with migraine was ascertained. The affected members did not show any aura or other neurologic symptoms during migraine attacks, indicating on a novel phenotype of syndromic hearing loss. To identify the causative gene, linkage analysis and whole-exome sequencing were performed. A novel missense variant, c.571G>A (p.(Val191Met)), was identified in the ATP1A2 gene that showed co-segregation with the phenotype in the family. In silico studies suggest that this variant causes a change in hydrophobic interactions and thereby slightly destabilize the A-domain of Na+/K+-ATPase. However, functional studies failed to show any effect of the p.(Val191Met) substitution on the catalytic rate of this enzyme. We describe a new phenotype of progressive hearing loss with migraine associated with a variant in the ATP1A2 gene. This study suggests that a variant in Na+/K+-ATPase can be involved in both migraine and hearing loss. C1 [Oh, Se-Kyung; Baek, Jeong-In; Kim, Un-Kyung] Kyungpook Natl Univ, Coll Nat Sci, Dept Biol, Taegu 702701, South Korea. [Oh, Se-Kyung; Kim, Un-Kyung] Kyungpook Natl Univ, Sch Life Sci, KNU Creat BioRes Grp, Plus Project BK21, Taegu 702701, South Korea. [Baek, Jeong-In; Choi, Soo-Young] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Weigand, Karl M.; Swarts, Herman G. P.; Koenderink, Jan B.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, Dept Pharmacol & Toxicol, NL-6525 ED Nijmegen, Netherlands. [Venselaar, Hanka; Vriend, Gert] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Park, Seong-Hyun] Kyungpook Natl Univ Hosp, Dept Neurosurg, Daegu, South Korea. [Raza, Muhammad Hashim] NIDCD, NIH, Bethesda, MD USA. [Jung, Da Jung; Lee, Sang-Heun; Lee, Kyu-Yup] Kyungpook Natl Univ, Coll Med, Dept Otorhinolaryngol Head & Neck Surg, Taegu 700721, South Korea. [Friedrich, Thomas] Tech Univ Berlin, Inst Chem, Berlin, Germany. [Kim, Un-Kyung] Kyungpook Natl Univ, Adv Bioresource Res Ctr, Taegu 702701, South Korea. RP Kim, UK (reprint author), Kyungpook Natl Univ, Coll Nat Sci, Dept Biol, Taegu 702701, South Korea. EM kimuk@knu.ac.kr; kylee@knu.ac.kr RI Vriend, G./H-8112-2014; Koenderink, Jan/N-3578-2014; Venselaar, Hanka/D-2009-2016 FU Korea Health Technology R&D Project through Korea Health Industry Development Institute - Ministry of Health & Welfare, Republic of Korea [HI12C1004(A121100)]; TJ Park Science Fellowship - POSCO Foundation of Korea FX We are grateful to the family for their collaboration in this study. We thank Dr Susan Spiller for electrophysiological experiments, and Dr Drayna for critical comments on the manuscript. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI12C1004(A121100)), and the TJ Park Science Fellowship funded by the POSCO Foundation of Korea (S-KO). NR 40 TC 6 Z9 6 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2015 VL 23 IS 5 BP 639 EP 645 DI 10.1038/ejhg.2014.154 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CG1JF UT WOS:000353028200016 PM 25138102 ER PT J AU Bakir-Gungor, B Remmers, EF Meguro, A Mizuki, N Kastner, DL Gul, A Sezerman, OU AF Bakir-Gungor, Burcu Remmers, Elaine F. Meguro, Akira Mizuki, Nobuhisa Kastner, Daniel L. Gul, Ahmet Sezerman, Osman U. TI Identification of possible pathogenic pathways in Behcet's disease using genome-wide association study data from two different populations SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SUSCEPTIBILITY LOCI; T-CELLS; VARIANTS; COAGULATION; ACTIVATION; IL23R-IL12RB2; MUTATIONS; MEDICINE; RISK; IL10 AB Behcet's disease (BD) is a multi-system inflammatory disorder of unknown etiology. Two recent genome-wide association studies (GWASs) of BD confirmed a strong association with the MHC class I region and identified two non-HLA common genetic variations. In complex diseases, multiple factors may target different sets of genes in the same pathway and thus may cause the same disease phenotype. We therefore hypothesized that identification of disease-associated pathways is critical to elucidate mechanisms underlying BD, and those pathways may be conserved within and across populations. To identify the disease-associated pathways, we developed a novel methodology that combines nominally significant evidence of genetic association with current knowledge of biochemical pathways, protein-protein interaction networks, and functional information of selected SNPs. Using this methodology, we searched for the disease-related pathways in two BD GWASs in Turkish and Japanese case-control groups. We found that 6 of the top 10 identified pathways in both populations were overlapping, even though there were few significantly conserved SNPs/genes within and between populations. The probability of random occurrence of such an event was 2.24E -39. These shared pathways were focal adhesion, MAPK signaling, TGF-beta signaling, ECM-receptor interaction, complement and coagulation cascades, and proteasome pathways. Even though each individual has a unique combination of factors involved in their disease development, the targeted pathways are expected to be mostly the same. Hence, the identification of shared pathways between the Turkish and the Japanese patients using GWAS data may help further elucidate the inflammatory mechanisms in BD pathogenesis. C1 [Bakir-Gungor, Burcu] Bahcesehir Univ, Dept Genet & Bioinformat, Fac Arts & Sci, Istanbul, Turkey. [Bakir-Gungor, Burcu] Abdullah Gul Univ, Fac Engn & Nat Sci, Dept Comp Engn, Kayseri, Turkey. [Remmers, Elaine F.; Kastner, Daniel L.] NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. [Meguro, Akira; Mizuki, Nobuhisa] Yokohama City Univ, Sch Med, Dept Ophthalmol, Yokohama, Kanagawa 232, Japan. [Gul, Ahmet] Istanbul Univ, Dept Internal Med, Div Rheumatol, Istanbul, Turkey. [Sezerman, Osman U.] Sabanci Univ, Fac Engn & Nat Sci, Biol Sci & Bioengn, Istanbul, Turkey. RP Bakir-Gungor, B (reprint author), Abdullah Gul Univ, Fac Engn & Nat Sci, Dept Comp Engn, Kayseri, Turkey. EM burcub@gatech.edu FU Intensified Cooperation (IntenC): Promotion of German-Turkish Higher Education Research Grant of The Scientific and Technological Research Council of Turkey (TUBITAK) [109S218]; Abdullah Gul University Support Foundation (AGUV) FX This work was supported by the Intensified Cooperation (IntenC): Promotion of German-Turkish Higher Education Research Grant of The Scientific and Technological Research Council of Turkey (TUBITAK; 109S218). The Abdullah Gul University Support Foundation (AGUV) supported the work of BB-G. NR 55 TC 3 Z9 3 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2015 VL 23 IS 5 BP 678 EP 687 DI 10.1038/ejhg.2014.158 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CG1JF UT WOS:000353028200021 PM 25227143 ER PT J AU Kim, J Sidransky, E Lopez, G AF Kim, Jenny Sidransky, Ellen Lopez, Grisel TI Understanding and managing parkinsonism in patients with glucocerebrosidase mutations SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Review DE chaperones; Gaucher disease; glucocerebrosidase; parkinsonism ID RANDOMIZED CONTROLLED-TRIAL; TYPE-1 GAUCHER-DISEASE; ENZYME REPLACEMENT THERAPY; QUALITY-OF-LIFE; RESTLESS LEGS SYNDROME; NONMOTOR SYMPTOMS; DOUBLE-BLIND; LEWY BODIES; EARLY-ONSET; RISK-FACTOR AB Introduction: Identification of an association between mutations in the glucocerebrosidase gene (GBA1) and the development of parkinsonism has contributed to a greater understanding of the role of lysosomal function in neuronal degeneration. This review will discuss the phenotypic presentation of patients with GBA1-associated parkinsonism. Some treatment strategies will be discussed although treatment studies in this cohort are limited. Areas covered: Current literature suggests that parkinsonism associated with GBA1 mutations may have specific characteristics distinct from idiopathic Parkinson's disease or parkinsonism due to other genetic mutations. In this review, we performed an electronic search in the PubMed database for papers using the terms 'Parkinson disease', 'parkinsonism', 'Gaucher disease', and 'GBA1'. Papers were selected if they discussed or described clinical presentation, treatment and current research efforts related to these terms. Expert opinion: Although there are no studies identifying treatments specific to patients with GBA1-associated parkinsonism, careful phenotypic characterization is crucial for the elucidation of the interaction between glucocerebrosidase and alpha-synuclein as well as for proper determination of disease prognosis and appropriate clinical counseling. C1 [Kim, Jenny; Sidransky, Ellen; Lopez, Grisel] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NHGRI, Med Genet Branch, NIH, Bldg 35A,Room 1E623, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov FU Intramural Research Program of the National Human Genome Research Institute; Intramural Research Program of the National Institutes of Health FX This work was supported by the Intramural Research Programs of the National Human Genome Research Institute and the National Institutes of Health. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents, received or pending, or royalties. NR 129 TC 0 Z9 0 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PD MAY PY 2015 VL 3 IS 5 BP 549 EP 562 DI 10.1517/21678707.2015.1034271 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CG6LK UT WOS:000353412200006 ER PT J AU Grey, MJ James, SP Rodgers, GP AF Grey, Michael J. James, Stephen P. Rodgers, Griffin P. TI NIDDK Programs and Emerging Opportunities for Digestive Diseases Research SO GASTROENTEROLOGY LA English DT Editorial Material ID PANCREATITIS C1 [Grey, Michael J.; James, Stephen P.] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. [Rodgers, Griffin P.] NIDDK, Off Director, NIH, Bethesda, MD 20892 USA. RP Grey, MJ (reprint author), NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2015 VL 148 IS 5 BP 868 EP 876 DI 10.1053/j.gastro.2015.03.009 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CG5MJ UT WOS:000353335700009 PM 25770083 ER PT J AU Abnet, CC Corley, DA Freedman, ND Kamangar, F AF Abnet, Christian C. Corley, Douglas A. Freedman, Neal D. Kamangar, Farin TI Diet and Upper Gastrointestinal Malignancies SO GASTROENTEROLOGY LA English DT Article DE Esophageal; Gastric; Cancer; Epidemiology ID SQUAMOUS-CELL CARCINOMA; GREEN TEA CONSUMPTION; CIRCULATING 25-HYDROXYVITAMIN D; NUTRITION INTERVENTION TRIAL; GENOME-WIDE ASSOCIATION; COLORECTAL-CANCER RISK; CHRONIC LIVER-DISEASE; SERVICES TASK-FORCE; CHRONIC HEPATITIS-C; ESOPHAGEAL CANCER AB Diet is believed to modulate cancer risk and this relationship has been widely studied in the gastrointestinal tract. Observational epidemiologic studies have provided most of the evidence about the effects of diet on cancer risk because clinical trials to determine nutritional exposures are often impossible, impractical, or unaffordable. Although a few foods or nutrients are thought to protect against specific types of cancer, it seems clear that the strength and even direction of dietary associations (increasing or decreasing risk) is organ-site and even histology-specific, along the gastrointestinal tract. Although some hypotheses are supported by a substantial body of observational data (drinking hot mate [an infusion of the herb Ilex Paraguarensis] contributes to esophageal cancer), there are not much data to support others. We discuss some highly touted hypotheses and draw interim conclusions about what is known and what could be done to improve the level of evidence. The complex nature of diet and its associations can be productively investigated with disease-specific studies. However, public health recommendations for normal-risk individuals regarding diet and gastrointestinal cancer should probably emphasize the importance of eating for overall health rather than eating specific foods to reduce risk for specific cancers. C1 [Abnet, Christian C.; Freedman, Neal D.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Corley, Douglas A.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Kamangar, Farin] Morgan State Univ, Dept Publ Hlth Anal, Sch Community Hlth & Policy, Baltimore, MD 21239 USA. [Kamangar, Farin] Univ Tehran Med Sci, Digest Dis Res Inst, Digest Oncol Res Ctr, Tehran, Iran. RP Abnet, CC (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6e344 MSC 9768, Bethesda, MD 20892 USA. EM abnetc@mail.nih.gov RI Freedman, Neal/B-9741-2015; Abnet, Christian/C-4111-2015 OI Freedman, Neal/0000-0003-0074-1098; Abnet, Christian/0000-0002-3008-7843 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute [U54 CA163262] FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute and by Grant U54 CA163262 (to D.A.C.). NR 164 TC 13 Z9 14 U1 3 U2 29 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2015 VL 148 IS 6 BP 1234 EP U184 DI 10.1053/j.gastro.2015.02.007 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CG5MO UT WOS:000353336200013 PM 25680671 ER PT J AU Wang, YF Liu, AY Mills, JL Boehnke, M Wilson, AF Bailey-Wilson, JE Xiong, MM Wu, CO Fan, RZ AF Wang, Yifan Liu, Aiyi Mills, James L. Boehnke, Michael Wilson, Alexander F. Bailey-Wilson, Joan E. Xiong, Momiao Wu, Colin O. Fan, Ruzong TI Pleiotropy Analysis of Quantitative Traits at Gene Level by Multivariate Functional Linear Models SO GENETIC EPIDEMIOLOGY LA English DT Article DE pleiotropy analysis; rare variants; common variants; association mapping; quantitative trait loci; complex traits; functional data analysis; multivariate linear models ID GENOME-WIDE ASSOCIATION; COMPLEX TRAITS; SUSCEPTIBILITY LOCI; METABOLIC SYNDROME; GLUCOSE-TOLERANCE; COMMON DISEASES; MULTIPLE TRAITS; SEQUENCING DATA; RARE VARIANTS; TYPE-2 AB In genetics, pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. A common approach is to analyze the phenotypic traits separately using univariate analyses and combine the test results through multiple comparisons. This approach may lead to low power. Multivariate functional linear models are developed to connect genetic variant data to multiple quantitative traits adjusting for covariates for a unified analysis. Three types of approximate F-distribution tests based on Pillai-Bartlett trace, Hotelling-Lawley trace, and Wilks's Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants in one genetic region. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and optimal sequence kernel association test (SKAT-O). Extensive simulations were performed to evaluate the false positive rates and power performance of the proposed models and tests. We show that the approximate F-distribution tests control the type I error rates very well. Overall, simultaneous analysis of multiple traits can increase power performance compared to an individual test of each trait. The proposed methods were applied to analyze (1) four lipid traits in eight European cohorts, and (2) three biochemical traits in the Trinity Students Study. The approximate F-distribution tests provide much more significant results than those of F-tests of univariate analysis and SKAT-O for the three biochemical traits. The approximate F-distribution tests of the proposed functional linear models are more sensitive than those of the traditional multivariate linear models that in turn are more sensitive than SKAT-O in the univariate case. The analysis of the four lipid traits and the three biochemical traits detects more association than SKAT-O in the univariate case. C1 [Wang, Yifan; Liu, Aiyi; Fan, Ruzong] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA. [Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA. [Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Wilson, Alexander F.; Bailey-Wilson, Joan E.] NHGRI, Computat & Stat Genom Branch, NIH, Bethesda, MD 20892 USA. [Xiong, Momiao] Univ Texas Houston, Ctr Human Genet, Houston, TX USA. [Wu, Colin O.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Fan, RZ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA. EM fanr@mail.nih.gov OI Bailey-Wilson, Joan/0000-0002-9153-2920; Liu, Aiyi/0000-0002-6618-5082 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, Bethesda, MD FX Two anonymous reviewers and the editors, Dr. Shete and Dr. Cordell, provided very good and insightful comments for us to improve the manuscript. We greatly thank the European cohort investigators and the Trinity Students Study (NICHD, NHGRI, Trinity College, Dublin and the Health Research Board of Ireland) investigators for letting us analyze the data and use them as examples. Dr. Stringham and Dr. Teslovich kindly sent us the data of the European cohorts and patiently answered many questions about the cohorts, and we greatly appreciated them. This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Ruzong Fan, Yifan Wang, Aiyi Liu, and James L. Mills), and by the Intramural Research Program of the National Human Genome Research Institute (Alexander F. Wilson and Joan E. Bailey-Wilson), National Institutes of Health, Bethesda, MD. We thank Dr. Seunggeun Lee who sent us their simulation program of SKAT and sequence data generated by Dr. Yun Li using program COSI. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). NR 73 TC 18 Z9 18 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD MAY PY 2015 VL 39 IS 4 BP 259 EP 275 DI 10.1002/gepi.21895 PG 17 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA CG4EK UT WOS:000353235900004 PM 25809955 ER PT J AU Mukhopadhyay, B Schuebel, K Mukhopadhyay, P Cinar, R Godlewski, G Xiong, KM Mackie, K Lizak, M Yuan, QP Goldman, D Kunos, G AF Mukhopadhyay, Bani Schuebel, Kornel Mukhopadhyay, Partha Cinar, Resat Godlewski, Grzegorz Xiong, Keming Mackie, Ken Lizak, Martin Yuan, Qiaoping Goldman, David Kunos, George TI Cannabinoid Receptor 1 Promotes Hepatocellular Carcinoma Initiation and Progression Through Multiple Mechanisms SO HEPATOLOGY LA English DT Article ID ANTI-TUMORAL ACTION; INDOLEAMINE 2,3-DIOXYGENASE; ENDOCANNABINOID SYSTEM; DEPENDENT ACTIVATION; TRANSCRIPTION FACTOR; IMMUNE ESCAPE; CB1 RECEPTORS; CANCER; LIVER; CELLS AB Hepatocellular carcinoma (HCC) has high mortality and no adequate treatment. Endocannabinoids interact with hepatic cannabinoid 1 receptors (CB1Rs) to promote hepatocyte proliferation in liver regeneration by inducing cell cycle proteins involved in mitotic progression, including Forkhead Box M1. Because this protein is highly expressed in HCC and contributes to its genesis and progression, we analyzed the involvement of the endocannabinoid/CB1R system in murine and human HCC. Postnatal diethylnitrosamine treatment induced HCC within 8 months in wild-type mice but fewer and smaller tumors in CB1R(-/-) mice or in wild-type mice treated with the peripheral CB1R antagonist JD5037, as monitored in vivo by serial magnetic resonance imaging. Genome-wide transcriptome analysis revealed CB1R-dependent, tumor-induced up-regulation of the hepatic expression of CB1R, its endogenous ligand anandamide, and a number of tumor-promoting genes, including the GRB2 interactome as well as Forkhead Box M1 and its downstream target, the tryptophan-catalyzing enzyme indoleamine 2,3-dioxygenase. Increased indoleamine 2,3-dioxygenase activity and consequent induction of immunosuppressive T-regulatory cells in tumor tissue promote immune tolerance. Conclusion: The endocannabinoid/CB1R system is up-regulated in chemically induced HCC, resulting in the induction of various tumor-promoting genes, including indoleamine 2,3-dioxygenase; and attenuation of these changes by blockade or genetic ablation of CB1R suppresses the growth of HCC and highlights the therapeutic potential of peripheral CB1R blockade. (Hepatology 2015;61:1615-1626) C1 [Mukhopadhyay, Bani; Mukhopadhyay, Partha; Cinar, Resat; Godlewski, Grzegorz; Xiong, Keming; Kunos, George] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Schuebel, Kornel; Yuan, Qiaoping; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Mackie, Ken] Indiana Univ, Gill Ctr Biomol Sci, Bloomington, IN USA. [Lizak, Martin] NINDS, In Vivo NMR Ctr, NIH, Bethesda, MD 20892 USA. RP Mukhopadhyay, B (reprint author), NIAAA, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA. EM mukhopadhyayb@mail.nih.gov; George.Kunos@nih.gov RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; CINAR, RESAT/0000-0002-8597-7253 FU National Institute on Alcohol Abuse and Alcoholism FX Supported by funds from the intramural research program of National Institute on Alcohol Abuse and Alcoholism. NR 40 TC 18 Z9 18 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD MAY PY 2015 VL 61 IS 5 BP 1615 EP 1626 DI 10.1002/hep.27686 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CG4DR UT WOS:000353233500021 PM 25580584 ER PT J AU Zhang, GY Yao, L Shen, JH Yang, YH Zhao, XJ AF Zhang, Gaoyan Yao, Li Shen, Jiahui Yang, Yihong Zhao, Xiaojie TI Reorganization of Functional Brain Networks Mediates the Improvement of Cognitive Performance Following Real-Time Neurofeedback Training of Working Memory SO HUMAN BRAIN MAPPING LA English DT Article DE functional reorganization; working memory network; default mode network; mediation effect; real-time neurofeedback; working memory ID POSTERIOR CINGULATE CORTEX; DEFAULT MODE NETWORK; PREFRONTAL CORTEX; RESTING-STATE; TOP-DOWN; RANDOM-FIELDS; CONNECTIVITY; FMRI; ACTIVATION; ATTENTION AB Working memory (WM) is essential for individuals' cognitive functions. Neuroimaging studies indicated that WM fundamentally relied on a frontoparietal working memory network (WMN) and a cinguloparietal default mode network (DMN). Behavioral training studies demonstrated that the two networks can be modulated by WM training. Different from the behavioral training, our recent study used a real-time functional MRI (rtfMRI)-based neurofeedback method to conduct WM training, demonstrating that WM performance can be significantly improved after successfully upregulating the activity of the target region of interest (ROI) in the left dorsolateral prefrontal cortex (Zhang et al., [2013]: PloS One 8:e73735); however, the neural substrate of rtfMRI-based WM training remains unclear. In this work, we assessed the intranetwork and internetwork connectivity changes of WMN and DMN during the training, and their correlations with the change of brain activity in the target ROI as well as with the improvement of post-training behavior. Our analysis revealed an ROI-network-behavior correlation relationship underlying the rtfMRI training. Further mediation analysis indicated that the reorganization of functional brain networks mediated the effect of self-regulation of the target brain activity on the improvement of cognitive performance following the neurofeedback training. The results of this study enhance our understanding of the neural basis of real-time neurofeedback and suggest a new direction to improve WM performance by regulating the functional connectivity in the WM related networks. Hum Brain Mapp 36:1705-1715, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Zhang, Gaoyan; Yao, Li; Zhao, Xiaojie] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. [Zhang, Gaoyan] Tianjin Univ, Sch Comp Sci & Technol, Tianjin Key Lab Cognit Comp & Applicat, Tianjin 300072, Peoples R China. [Yao, Li; Shen, Jiahui; Zhao, Xiaojie] Beijing Normal Univ, Coll Informat Sci & Technol, Beijing 100875, Peoples R China. [Yang, Yihong] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. RP Zhao, XJ (reprint author), Beijing Normal Univ, Coll Informat Sci & Technol, Beijing 100875, Peoples R China. EM yihongyang@mail.nih.gov; zhaoxj86@hotmail.com FU National Natural Science Foundation of China [61210001, 61473044]; National Program on Key Basic Research Project (973 Program) [2013CB329301]; National Institute on Drug Abuse, National Institutes of Health FX Contract grant sponsor: Funds for International Cooperation and Exchange of the National Natural Science Foundation of China; Contract grant number: 61210001; Contract grant sponsor: National Program on Key Basic Research Project (973 Program); Contract grant number: 2013CB329301; Contract grant sponsor: National Natural Science Foundation of China; Contract grant number: 61473044; Contract grant sponsor: Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health (to Y.Y.). NR 44 TC 2 Z9 2 U1 3 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAY PY 2015 VL 36 IS 5 BP 1705 EP 1715 DI 10.1002/hbm.22731 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CG1XH UT WOS:000353068300006 PM 25545862 ER PT J AU Wu, T Hou, YA Hallett, M Zhang, JR Chan, P AF Wu, Tao Hou, Yanan Hallett, Mark Zhang, Jiarong Chan, Piu TI Lateralization of Brain Activity Pattern During Unilateral Movement in Parkinson's Disease SO HUMAN BRAIN MAPPING LA English DT Article DE Parkinson's disease; lateralization of brain activity; basal ganglia circuits; transcallosal inhibition; compensation ID TRANSCRANIAL MAGNETIC STIMULATION; SUPPLEMENTARY MOTOR AREA; CEREBRAL-BLOOD-FLOW; EXTERNALLY TRIGGERED MOVEMENTS; SEQUENTIAL FINGER MOVEMENTS; DORSAL PREMOTOR CORTEX; MIRROR MOVEMENTS; BASAL GANGLIA; INTERHEMISPHERIC INHIBITION; FUNCTIONAL MRI AB We investigated the lateralization of brain activity pattern during performance of unilateral movement in drug-naive Parkinson's disease (PD) patients with only right hemiparkinsonian symptoms. Functional MRI was obtained when the subjects performed strictly unilateral right hand movement. A laterality index was calculated to examine the lateralization. Patients had decreased activity in the left putamen and left supplementary motor area, but had increased activity in the right primary motor cortex, right premotor cortex, left postcentral gyrus, and bilateral cerebellum. The laterality index was significantly decreased in PD patients compared with controls (0.41 +/- 0.14 vs. 0.84 +/- 0.09). The connectivity from the left putamen to cortical motor regions and cerebellum was decreased, while the interactions between the cortical motor regions, cerebellum, and right putamen were increased. Our study demonstrates that in early PD, the lateralization of brain activity during unilateral movement is significantly reduced. The dysfunction of the striatum-cortical circuit, decreased transcallosal inhibition, and compensatory efforts from cortical motor regions, cerebellum, and the less affected striatum are likely reasons contributing to the reduced motor lateralization. The disruption of the lateralized brain activity pattern might be a reason underlying some motor deficits in PD, like mirror movements or impaired bilateral motor coordination. Hum Brain Mapp 36:1878-1891, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Wu, Tao; Hou, Yanan; Zhang, Jiarong; Chan, Piu] Capital Med Univ, Beijing Inst Geriatr, Xuanwu Hosp,Minist Educ, Dept Neurobiol,Key Lab Neurodegenerat Disorders, Beijing 100053, Peoples R China. [Wu, Tao; Hou, Yanan; Zhang, Jiarong; Chan, Piu] Beijing Inst Brain Disorders, Beijing Key Lab Parkinsons Dis, Parkinson Dis Ctr, Beijing, Peoples R China. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Wu, T (reprint author), Capital Med Univ, Beijing Inst Geriatr, Xuanwu Hosp,Minist Educ, Dept Neurobiol,Key Lab Neurodegenerat Disorders, Beijing 100053, Peoples R China. EM wutao69@gmail.com FU National Science Foundation of China [81071012, 81271429] FX Contract grant sponsor: The National Science Foundation of China; Contract grant number: 81071012; 81271429 NR 118 TC 5 Z9 5 U1 3 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAY PY 2015 VL 36 IS 5 BP 1878 EP 1891 DI 10.1002/hbm.22743 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CG1XH UT WOS:000353068300018 PM 25644527 ER PT J AU Vanderbeck, S Bockhorst, J Kleiner, D Komorowski, R Chalasani, N Gawrieh, S AF Vanderbeck, Scott Bockhorst, Joseph Kleiner, David Komorowski, Richard Chalasani, Naga Gawrieh, Samer TI Automatic quantification of lobular inflammation and hepatocyte ballooning in nonalcoholic fatty liver disease liver biopsies SO HUMAN PATHOLOGY LA English DT Article DE Fatty liver; Lobular inflammation; Hepatocyte ballooning; Machine learning; NAFLD activity score; Digital image analysis ID SCORING SYSTEM; HEPATITIS-C; STEATOHEPATITIS; PREVALENCE; VALIDATION; CIRRHOSIS; OUTCOMES AB Automatic quantification of cardinal histologic features of nonalcoholic fatty liver disease (NAFLD) may reduce human variability and allow continuous rather than semiquantitative assessment of injury. We recently developed an automated classifier that can detect and quantify macrosteatosis with greater than or equal to 95% precision and recall (sensitivity). Here, we report our early results on the classifier's performance in detecting lobular inflammation and hepatocellular ballooning. Automatic quantification of lobular inflammation and ballooning was performed on digital images of hematoxylin and eosin stained slides of liver biopsy samples from 59 individuals with normal liver histology and varying severity of NAFLD. Two expert hepatopathologists scored liver biopsies according the nonalcoholic steatohepatitis clinical research network scoring system and provided annotations of lobular inflammation and hepatocyte ballooning on the digital images. The classifier had precision and recall of 70% and 49% for lobular inflammation, and 91% and 54% for hepatocyte ballooning. In addition, the classifier had an area under the curve of 95% for lobular inflammation and 98% for hepatocyte, ballooning. The Spearman rank correlation coefficient for comparison with pathologist grades was 45.2% for lobular inflammation and 46% for hepatocyte ballooning. Our novel observations demonstrate that automatic quantification of cardinal NAFLD histologic lesions is feasible and offer promise for further development of automatic quantification as a potential aid to pathologists evaluating NAFLD biopsies in clinical practice and clinical trials. (C) 2015 Elsevier Inc. All rights reserved.. C1 [Vanderbeck, Scott; Bockhorst, Joseph] Univ Wisconsin, Dept Elect Engn & Comp Sci, Milwaukee, WI 53211 USA. [Kleiner, David] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Komorowski, Richard] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. [Chalasani, Naga; Gawrieh, Samer] Indiana Univ Sch Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA. RP Gawrieh, S (reprint author), Indiana Univ Sch Med, Div Gastroenterol & Hepatol, 702 Rotary Circle, Indianapolis, IN 46202 USA. EM sgawrieh@iu.edu OI Kleiner, David/0000-0003-3442-4453 FU Milwaukee Research Foundation University of Wisconsin (Milwaukee, WI) [PRJ-391B]; Intramural Research Program of the National Cancer Institute, National Institutes of Health; University of Wisconsin Extension Ideadvance Seed Fund; WI Economic Development Corporation (Madison, WI); University of Wisconsin System (Madison, WI) FX This research was supported by the Milwaukee Research Foundation University of Wisconsin (Milwaukee, WI) (J. B. and S. G.) grant number PRJ-391B and in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health (D. K.).; SV is owner and founder of Organic Research Corporation (Milwaukee, WI), a start-up funded in part by a grant from the University of Wisconsin Extension Ideadvance Seed Fund through its partnership with the WI Economic Development Corporation (Madison, WI) and the University of Wisconsin System (Madison, WI). The work contained herein was completed in its entirety while Vanderbeck was a student at University of Wisconsin Milwaukee, WI, before founding Organic Research Corporation. NR 24 TC 0 Z9 0 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2015 VL 46 IS 5 BP 767 EP 775 DI 10.1016/j.humpath.2015.01.019 PG 9 WC Pathology SC Pathology GA CG5EQ UT WOS:000353314300017 PM 25776030 ER PT J AU Alonso, WJ Guillebaud, J Viboud, C Razanajatovo, NH Orelle, A Zhou, SZ Randrianasolo, L Heraud, JM AF Alonso, Wladimir Jimenez Guillebaud, Julia Viboud, Cecile Razanajatovo, Norosoa Harline Orelle, Arnaud Zhou, Steven Zhixiang Randrianasolo, Laurence Heraud, Jean-Michel TI Influenza seasonality in Madagascar: the mysterious African free-runner SO Influenza and Other Respiratory Viruses LA English DT Article DE Influenza; Madagascar; population connectivity; seasonality; time series; viral migration ID VIRUS SUBTYPE H1N1; A VIRUS; SENTINEL SURVEILLANCE; WEST-AFRICA; CIRCULATION; DYNAMICS; PERSISTENCE; MORTALITY; SYNCHRONY; ILLNESS AB BackgroundThe seasonal drivers of influenza activity remain debated in tropical settings where epidemics are not clearly phased. Antananarivo is a particularly interesting case study because it is in Madagascar, an island situated in the tropics and with quantifiable connectivity levels to other countries. ObjectivesWe aimed at disentangling the role of environmental forcing and population fluxes on influenza seasonality in Madagascar. MethodsWe compiled weekly counts of laboratory-confirmed influenza-positive specimens for the period 2002 to 2012 collected in Antananarivo, with data available from sub-Saharan countries and countries contributing most foreign travelers to Madagascar. Daily climate indicators were compiled for the study period. ResultsOverall, influenza activity detected in Antananarivo predated that identified in temperate Northern Hemisphere locations. This activity presented poor temporal matching with viral activity in other countries from the African continent or countries highly connected to Madagascar excepted for A(H1N1)pdm09. Influenza detection in Antananarivo was not associated with travel activity and, although it was positively correlated with all climatic variables studied, such association was weak. ConclusionsThe timing of influenza activity in Antananarivo is irregular, is not driven by climate, and does not align with that of countries in geographic proximity or highly connected to Madagascar. This work opens fresh questions regarding the drivers of influenza seasonality globally particularly in mid-latitude and less-connected regions to tailor vaccine strategies locally. C1 [Alonso, Wladimir Jimenez; Viboud, Cecile] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Guillebaud, Julia; Razanajatovo, Norosoa Harline; Orelle, Arnaud; Heraud, Jean-Michel] Inst Pasteur Madagascar, Natl Influenza Ctr, Antananarivo 101, Madagascar. [Orelle, Arnaud] Integrated Qual Lab Serv IQLS, Lyon, France. [Zhou, Steven Zhixiang] London Sch Hyg & Trop Med, London WC1, England. [Randrianasolo, Laurence] Inst Pasteur Madagascar, Epidemiol Unit, Antananarivo 101, Madagascar. RP Heraud, JM (reprint author), Inst Pasteur Madagascar, Virol Unit, Natl Influenza Ctr, BP 1274, Antananarivo 101, Madagascar. EM jmheraud@pasteur.mg RI HERAUD, Jean-Michel/O-1464-2013 OI HERAUD, Jean-Michel/0000-0003-1107-0859 NR 40 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1750-2640 EI 1750-2659 J9 INFLUENZA OTHER RESP JI Influenza Other Respir. Viruses PD MAY PY 2015 VL 9 IS 3 BP 101 EP 109 DI 10.1111/irv.12308 PG 9 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA CG6JU UT WOS:000353407400002 PM 25711873 ER PT J AU Vajda, S Plotz, T Fink, GA AF Vajda, Szilard Ploetz, Thomas Fink, Gernot A. TI Camera-Based Whiteboard Reading for Understanding Mind Maps SO INTERNATIONAL JOURNAL OF PATTERN RECOGNITION AND ARTIFICIAL INTELLIGENCE LA English DT Article DE Camera-based document recognition; whiteboard reading; mind map recognition; handwriting recognition; document layout analysis ID HANDWRITING RECOGNITION; LAYOUT ANALYSIS; SEPARATION; CHARACTER; ALGORITHM AB Mind maps, i.e. the spatial organization of ideas and concepts around a central topic and the visualization of their relations, represent a very powerful and thus popular means to support creative thinking and problem solving processes. Typically created on traditional whiteboards, they represent an important technique for collaborative brainstorming sessions. We describe a camera-based system to analyze hand-drawn mind maps written on a whiteboard. The goal of the presented system is to produce digital representations of such mind maps, which would enable digital asset management, i.e. storage and retrieval of manually created documents. Our system is based on image acquisition by means of a camera, followed by the segmentation of the particular whiteboard image focusing on the extraction of written context, i.e. the ideas captured by the mind map. The spatial arrangement of these ideas is recovered using layout analysis based on unsupervised clustering, which results in graph representations of mind maps. Finally, handwriting recognition derives textual transcripts of the ideas captured by the mind map. We demonstrate the capabilities of our mind map reading system by means of an experimental evaluation, where we analyze images of mind maps that have been drawn on whiteboards, without any further constraints other than the underlying topic. In addition to the promising recognition results, we also discuss training strategies, which effectively allow for system bootstrapping using out-of-domain sample data. The latter is important when addressing creative thinking processes where domain-related training data are difficult to obtain as they focus on novelty by definition. C1 [Vajda, Szilard] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA. [Ploetz, Thomas] Newcastle Univ, Sch Comp Sci, Newcastle Upon Tyne NE7 1NP, Tyne & Wear, England. [Fink, Gernot A.] TU Dortmund Univ, Dept Comp Sci, D-44221 Dortmund, Germany. RP Vajda, S (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM szilard.vajda@nih.gov; t.ploetz@ncl.ac.uk; gernot.fink@udo.edu FU German Research Foundation (DFG) [Fi799/3] FX This work has been supported by the German Research Foundation (DFG) within project Fi799/3. The authors would also like to thank Leonard Rothacker for his valuable support in the implementation of the whiteboard reading system. NR 55 TC 2 Z9 2 U1 1 U2 19 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0218-0014 EI 1793-6381 J9 INT J PATTERN RECOGN JI Int. J. Pattern Recognit. Artif. Intell. PD MAY PY 2015 VL 29 IS 3 AR 1553003 DI 10.1142/S0218001415530031 PG 26 WC Computer Science, Artificial Intelligence SC Computer Science GA CG8IS UT WOS:000353551500007 ER PT J AU Sherman, ME Piedmonte, M Mai, PL Greene, MH AF Sherman, Mark E. Piedmonte, Marion Mai, Phuong L. Greene, Mark H. TI Pathologic Findings at Risk-Reducing Surgery Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Sherman, Mark E.; Mai, Phuong L.; Greene, Mark H.] NCI, Rockville, MD 20850 USA. [Piedmonte, Marion] Roswell Pk Canc Inst, NRG Oncol Stat & Data Ctr, Buffalo, NY 14263 USA. RP Sherman, ME (reprint author), NCI, Rockville, MD 20850 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2015 VL 33 IS 13 BP 1515 EP 1515 DI 10.1200/JCO.2014.60.2482 PG 1 WC Oncology SC Oncology GA CG4CQ UT WOS:000353230100020 PM 25732162 ER PT J AU Xue, Y Wang, L Xia, D Li, Q Gao, S Dong, M Cai, T Shi, S He, L Hu, K Mao, T Duan, X AF Xue, Y. Wang, L. Xia, D. Li, Q. Gao, S. Dong, M. Cai, T. Shi, S. He, L. Hu, K. Mao, T. Duan, X. TI Dental Abnormalities Caused by Novel Compound Heterozygous CTSK Mutations SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE pycnodysostosis; cathepsin K; molecular biology; tooth; dental cementum; alveolar bone ID CATHEPSIN-K; PYCNODYSOSTOSIS; BONE; PYKNODYSOSTOSIS; ODONTOCLASTS; MICROSCOPY; RESORPTION; FEATURES; CEMENTUM; PATIENT AB Cathepsin K (CTSK) is an important protease responsible for degrading type I collagen, osteopontin, and other bone matrix proteins. The mutations in the CTSK gene can cause pycnodysostosis (OMIM 265800), a rare autosomal recessive bone dysplasia. Patients with pycnodysostosis have been reported to present specific dental abnormalities; however, whether these dental abnormalities are related to dysfunctional CTSK has never been reported. Here we investigated the histologic changes of cementum and alveolar bone in a pycnodysostosis patient, caused by novel compound heterozygous mutations in the CTSK gene (c.87 G>A p.W29X and c.848 A>G p.Y283C). The most impressive manifestations in tooth were extensive periradicular high-density clumps with unclear periodontal space by orthopantomography examination and micro-computed tomography scanning analysis. Hematoxylin/eosin and toluidine blue staining and atomic force microscopy analysis showed that the cementum became significantly thickened, softened, and full of cementocytes. The disorganized bone structure was the main character of alveolar bone. The p.W29X mutation may represent the loss-of-function allele with an earlier termination codon in the precursor CTSK polypeptide. Residue Y283 is highly conserved among papain-like cysteine proteases. Three-dimensional structure modeling analysis found that the loss of the hydroxybenzene residue in the Y283C mutation would interrupt the hydrogen network and possibly affect the self-cleavage of the CTSK enzyme. Furthermore, p.Y283C mutation did not affect the mRNA and protein levels of overexpressed CTSK in COS-7 system but did reduce CTSK enzyme activity. In conclusion, the histologic and ultrastructural changes of cementum and alveolar bone might be affected by CTSK mutation via reduction of its enzyme activity (clinical trial registration: ChiCTR-TNC-10000876). C1 [Xue, Y.; Duan, X.] Fourth Mil Med Univ, Sch Stomatol, Clin Oral Rare & Genet Dis, State Key Lab Mil Stomatol,Dept Oral Biol, Xian 710032, Shaanxi, Peoples R China. [Wang, L.] Fourth Mil Med Univ, Dept Mol Biol, Xian 710032, Shaanxi, Peoples R China. [Xia, D.; Li, Q.; Gao, S.; Dong, M.] Aarhus Univ, Interdisciplinary Nanosci Ctr iNANO, Aarhus C, Denmark. [Cai, T.] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. [Shi, S.] Univ So Calif, Ctr Craniofacial Mol Biol, Sch Dent, Los Angeles, CA 90033 USA. [He, L.; Hu, K.; Mao, T.] Fourth Mil Med Univ, Sch Stomatol, Dept Oral & Maxillofacial Surg, State Key Lab Mil Stomatol, Xian 710032, Shaanxi, Peoples R China. RP Duan, X (reprint author), Fourth Mil Med Univ, Sch Stomatol, Clin Oral Rare & Genet Dis, State Key Lab Mil Stomatol,Dept Oral Biol, 145 West Changle Rd, Xian 710032, Shaanxi, Peoples R China. EM xhduan@fmmu.edu.cn RI Xia, Dan/O-9779-2014; Li, Qiang/L-7741-2013; Dong, Mingdong/B-3341-2010 OI Xia, Dan/0000-0001-7892-7381; Li, Qiang/0000-0003-1056-4152; Dong, Mingdong/0000-0002-2025-2171 FU National Natural Science Foundation of China [NSFC 81271116, NSFC 81300861] FX This work was supported in part by grants of the National Natural Science Foundation of China (NSFC 81271116 for X.D., NSFC 81300861 for Y.X.). We thank the patient, his family members, and the controls for joining this research. We are also grateful for the technique support from Equipment Center of PLA Institute of Stomatological Research. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 22 TC 4 Z9 5 U1 4 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD MAY PY 2015 VL 94 IS 5 BP 674 EP 681 DI 10.1177/0022034515573964 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CG3VN UT WOS:000353207800006 PM 25731711 ER PT J AU Foster, BL Sheen, CR Hatch, NE Liu, J Cory, E Narisawa, S Kiffer-Moreira, T Sah, RL Whyte, MP Somerman, MJ Millan, JL AF Foster, B. L. Sheen, C. R. Hatch, N. E. Liu, J. Cory, E. Narisawa, S. Kiffer-Moreira, T. Sah, R. L. Whyte, M. P. Somerman, M. J. Millan, J. L. TI Periodontal Defects in the A116T Knock-in Murine Model of Odontohypophosphatasia SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE alkaline phosphatase; hypophosphatasia; bone; cementum; dentin; periodontium ID INFANTILE HYPOPHOSPHATASIA; BONE; MICE; OSTEOPONTIN; PHENOTYPE; CEMENTUM; VIVO AB Mutations in ALPL result in hypophosphatasia (HPP), a disease causing defective skeletal mineralization. ALPL encodes tissue nonspecific alkaline phosphatase (ALP), an enzyme that promotes mineralization by reducing inorganic pyrophosphate, a mineralization inhibitor. In addition to skeletal defects, HPP causes dental defects, and a mild clinical form of HPP, odontohypophosphatasia, features only a dental phenotype. The Alpl knockout (Alpl(-/-)) mouse phenocopies severe infantile HPP, including profound skeletal and dental defects. However, the severity of disease in Alpl(-/-) mice prevents analysis at advanced ages, including studies to target rescue of dental tissues. We aimed to generate a knock-in mouse model of odontohypophosphatasia with a primarily dental phenotype, based on a mutation (c.346G>A) identified in a human kindred with autosomal dominant odontohypophosphatasia. Biochemical, skeletal, and dental analyses were performed on the resulting Alpl(+/A116T) mice to validate this model. Alpl(+/A116T) mice featured 50% reduction in plasma ALP activity compared with wild-type controls. No differences in litter size, survival, or body weight were observed in Alpl(+/A116T) versus wild-type mice. The postcranial skeleton of Alpl(+/A116T) mice was normal by radiography, with no differences in femur length, cortical/trabecular structure or mineral density, or mechanical properties. Parietal bone trabecular compartment was mildly altered. Alpl(+/A116T) mice featured alterations in the alveolar bone, including radiolucencies and resorptive lesions, osteoid accumulation on the alveolar bone crest, and significant differences in several bone properties measured by micro-computed tomography. Nonsignificant changes in acellular cementum did not appear to affect periodontal attachment or function, although circulating ALP activity was correlated significantly with incisor cementum thickness. The Alpl(+/A116T) mouse is the first model of odontohypophosphatasia, providing insights on dentoalveolar development and function under reduced ALP, bringing attention to direct effects of HPP on alveolar bone, and offering a new model for testing potential dental-targeted therapies in future studies. C1 [Foster, B. L.; Somerman, M. J.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Sheen, C. R.; Narisawa, S.; Kiffer-Moreira, T.; Millan, J. L.] Sanford Burnham Med Res Inst, Sanford Childrens Hlth Res Ctr, La Jolla, CA 92037 USA. [Hatch, N. E.; Liu, J.] Univ Michigan, Sch Dent, Dept Orthodont & Pediat Dent, Ann Arbor, MI 48109 USA. [Cory, E.; Sah, R. L.] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Whyte, M. P.] Shriners Hosp Children, Ctr Metab Bone Dis & Mol Res, St Louis, MO USA. [Whyte, M. P.] Washington Univ, Sch Med, Div Bone & Mineral Dis, St Louis, MO USA. RP Millan, JL (reprint author), Sanford Burnham Med Res Inst, Sanford Childrens Hlth Res Ctr, La Jolla, CA 92037 USA. EM millan@sanfordburnham.org RI Foster, Brian/H-8375-2015 OI Foster, Brian/0000-0003-3444-0576 FU National Institute for Dental and Craniofacial Research of the National Institutes of Health (NIH; Bethesda, MD) [DE 12889]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) /NIH [AR 066110]; Intramural Research Program of NIAMS; Shriners Hospitals for Children FX This research was supported by a grant (DE 12889) to J.L.M. from the National Institute for Dental and Craniofacial Research of the National Institutes of Health (NIH; Bethesda, MD), a grant (AR 066110) to B.L.F. from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) /NIH, the Intramural Research Program of NIAMS (M.J.S.), and support from Shriners Hospitals for Children (M.P.W.). We thank Kenn Holmbeck (National Institute for Dental and Craniofacial Research) and Lyudmila Lukashova (Hospital for Special Surgery, New York, NY, USA; NIH AR 046121) for assistance with micro-computed tomography analysis, Nasrin Kalantari Pour (NIAMS) for assistance with histology, and Helen Wimer (Smithsonian Institute, Washington, DC) for assistance with plastic sectioning and staining. We thank Ling Wang of the Sanford-Burnham Medical Research Institute Animal Facility for assistance with blastocyst injection and Greg Martin and Sergey Kupriyanov of The Scripps Research Institute Mouse Genetics Core for assistance with embryonic stem cell electroporation. We also thank Carmen Huesa for assistance with 3-point bending analysis. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 28 TC 6 Z9 6 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD MAY PY 2015 VL 94 IS 5 BP 706 EP 714 DI 10.1177/0022034515573273 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CG3VN UT WOS:000353207800010 PM 25716980 ER PT J AU Kondo, Y Nakamoto, T Jaramillo, Y Choi, S Catalan, MA Melvin, JE AF Kondo, Y. Nakamoto, T. Jaramillo, Y. Choi, S. Catalan, M. A. Melvin, J. E. TI Functional Differences in the Acinar Cells of the Murine Major Salivary Glands SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE epithelia; physiology; salivary physiology; chloride channel; Na-K-Cl transporter; calcium signaling ID FLUID SECRETION; CL--HCO3-EXCHANGE; MOUSE; CHANNEL; TMEM16A; COTRANSPORTERS; ELECTROLYTE; EXPRESSION; TRANSPORT; MICE AB In humans, approximately 90% of saliva is secreted by the 3 major salivary glands: the parotid (PG), the submandibular (SMG), and the sublingual glands (SLG). Even though it is known that all 3 major salivary glands secrete saliva by a Cl--dependent mechanism, salivary secretion rates differ greatly among these glands. The goal of this study was to gain insight into the properties of the ion-transporting pathways in acinar cells that might account for the differences among the major salivary glands. Pilocarpine-induced saliva was simultaneously collected in vivo from the 3 major salivary glands of mice. When normalized by gland weight, the amount of saliva secreted by the PG was more than 2-fold larger than that obtained from the SMG and SLG. At the cellular level, carbachol induced an increase in the intracellular [Ca2+] that was more than 2-fold larger in PG and SMG than in SLG acinar cells. Carbachol-stimulated Cl- efflux and the protein levels of the Ca2+-activated Cl- channel TMEM16A, the major apical Cl- efflux pathway in salivary acinar cells, were significantly greater in PG compared with SMG and SLG. In addition, we evaluated the transporter activity of the Na+-K+-2Cl(-) cotransporters (NKCC1) and anion exchangers (AE), the 2 primary basolateral Cl- uptake mechanisms in acinar cells. The SMG NKCC1 activity was about twice that of the PG and more than 12-fold greater than that of the SLG. AE activity was similar in PG and SLG, and both PG and SLG AE activity was about 2-fold larger than that of SMG. In summary, the salivation kinetics of the 3 major glands are distinct, and these differences can be explained by the unique functional properties of each gland related to Cl- movement, including the transporter activities of the Cl- uptake and efflux pathways, and intracellular Ca2+ mobilization. C1 [Kondo, Y.; Jaramillo, Y.; Choi, S.; Catalan, M. A.; Melvin, J. E.] Natl Inst Dent & Craniofacial Res, Secretory Mech & Dysfunct Sect, NIH, Bethesda, MD 20892 USA. [Kondo, Y.; Nakamoto, T.] Kyushu Dent Univ, Dept Oral Reconstruct & Rehabil, Kitakyushu, Fukuoka, Japan. RP Melvin, JE (reprint author), Natl Inst Dent & Craniofacial Res, Secretory Mech & Dysfunct Sect, NIH, 10 Ctr Dr,Bldg 10,Room 1N117B, Bethesda, MD 20892 USA. EM james.melvin@nih.gov OI Catalan, Marcelo/0000-0003-3544-2821 FU Intramural Research Program of the National Institutes of Health [NIH, National Institute of Dental and Craniofacial Research (NIDCR)] FX The Secretory Mechanisms and Dysfunction Section is supported by the Intramural Research Program of the National Institutes of Health [NIH, National Institute of Dental and Craniofacial Research (NIDCR)]. We are thankful to Drs. Z. Borok, E.D. Crandall, and U.P. Flodby for providing the ACID mice and to Dr. Natalie Porat-Shliom for helping with the data analysis using ImageJ software. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 25 TC 3 Z9 3 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD MAY PY 2015 VL 94 IS 5 BP 715 EP 721 DI 10.1177/0022034515570943 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CG3VN UT WOS:000353207800011 PM 25680367 ER PT J AU Myers, SL Yang, CZ Bittner, GD Witt, KL Tice, RR Baird, DD AF Myers, Sharon L. Yang, Chun Z. Bittner, George D. Witt, Kristine L. Tice, Raymond R. Baird, Donna D. TI Estrogenic and anti-estrogenic activity of off-the-shelf hair and skin care products SO Journal of Exposure Science and Environmental Epidemiology LA English DT Article DE cosmetics; endocrine disruptors; estrogen receptor binding; estrogenic activity; anti-estrogenic activity; personal care products ID BREAST-CANCER; PREPUBERTAL GYNECOMASTIA; ENVIRONMENTAL ESTROGENS; PHTHALATE METABOLITES; URINARY-EXCRETION; WOMEN; PARABENS; POPULATION; CREAM; ASSAY AB Use of personal care products is widespread in the United States but tends to be greater among African Americans than whites. Of special concern is the possible hazard of absorption of chemicals with estrogenic activity (EA) or anti-EA (AEA) in these products. Such exposure may have adverse health effects, especially when it occurs during developmental windows (e.g., prepubertally) when estrogen levels are low. We assessed the ethanol extracts of eight commonly used hair and skin products popular among African Americans for EA and AEA using a cell proliferation assay with the estrogen sensitive MCF-7: WS8 cell line derived from a human breast cancer. Four of the eight personal care products tested (Oil Hair Lotion, Extra-dry Skin Lotion, Intensive Skin Lotion, Petroleum Jelly) demonstrated detectable EA, whereas three (Placenta Hair Conditioner, Tea-Tree Hair Conditioner, Cocoa Butter Skin Cream) exhibited AEA. Our data indicate that hair and skin care products can have EA or AEA, and suggest that laboratory studies are warranted to investigate the in vivo activity of such products under chronic exposure conditions as well as epidemiologic studies to investigate potential adverse health effects that might be associated with use of such products. C1 [Myers, Sharon L.; Baird, Donna D.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Myers, Sharon L.] Univ Calif Davis, Hlth Syst, Sacramento, CA 95817 USA. [Yang, Chun Z.; Bittner, George D.] CertiChem, Austin, TX USA. [Bittner, George D.] Univ Texas Austin, Neurobiol Sect, Austin, TX 78712 USA. [Bittner, George D.] Univ Texas Austin, Sch Biol, Austin, TX 78712 USA. [Witt, Kristine L.; Tice, Raymond R.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Baird, DD (reprint author), NIEHS, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM baird@niehs.nih.gov RI Baird, Donna/D-5214-2017 OI Baird, Donna/0000-0002-5544-2653 FU Divisions of Intramural Research and the National Toxicology Program of the National Institute of Environmental Health Sciences at the National Institutes of Health (NIH); NIH [1R43/44 ES014806, 01-03] FX This work was supported by the Divisions of Intramural Research and the National Toxicology Program of the National Institute of Environmental Health Sciences at the National Institutes of Health (NIH), and by NIH grant 1R43/44 ES014806, 01-03 to C.Z.Y. This article may be the work product of an employee or group of employees of the NIH; however, the statements, opinions or conclusions contained therein do not necessarily represent the statements, opinions or conclusions of NIH or the United States government. We thank Aimee D'Aloisio, Elizabeth Maull, and Kyla Taylor who critically reviewed an earlier draft of the manuscript. NR 57 TC 3 Z9 3 U1 9 U2 40 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1559-0631 EI 1559-064X J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD MAY-JUN PY 2015 VL 25 IS 3 BP 271 EP 277 DI 10.1038/jes.2014.32 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA CG6JF UT WOS:000353405500006 PM 24849798 ER PT J AU Trabert, B Chen, Z Kannan, K Peterson, CM Pollack, AZ Sun, L Louis, GMB AF Trabert, Britton Chen, Zhen Kannan, Kurunthachalam Peterson, C. Matthew Pollack, Anna Z. Sun, Liping Louis, Germaine M. Buck TI Persistent organic pollutants (POPs) and fibroids: results from the ENDO study SO Journal of Exposure Science and Environmental Epidemiology LA English DT Article DE epidemiology; uterine fibroids; persistent organic pollutants; omental fat; serum ID POLYBROMINATED DIPHENYL ETHERS; UTERINE LEIOMYOMAS; ORGANOCHLORINE PESTICIDES; POLYCHLORINATED-BIPHENYLS; ADIPOSE-TISSUE; SERUM; ENDOMETRIOSIS; EXPOSURE; POPULATION; CHEMICALS AB To evaluate the association between persistent organic pollutants (POPs) and uterine fibroids, we used previously collected data from a cohort of women aged 18-44 years undergoing laparoscopy or laparotomy at 14 participating hospital surgical centers (n = 473). POP concentrations were measured in omental fat and serum. Presence of fibroids was defined on the basis of a postoperative diagnosis (n = 99). Odds ratios (OR) and 95% confidence interval (CI) for each POP by biologic medium were estimated using unconditional logistic regression adjusted for identified covariates. Concentrations were higher in omental fat than in serum for all POPs. Serum p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) was the only POP associated with fibroids (per 1-SD increase in log-transformed p,p'-DDE OR (95% CI): 1.37 (1.05-1.80)). In analyses excluding women diagnosed with endometriosis, a number of polychlorinated biphenyls (PCBs) measured in omental fat were associated with fibroids (PCB 99: 1.64 (1.08, 2.49); PCB 138: 1.64 (1.03, 2.59); PCB 146: 1.54 (1.01, 2.37); PCB 153: 1.88 (1.12, 3.13); PCB 196: 1.60 (1.02, 2.51); PCB 206: 1.52 (1.01, 2.29)). Although exploratory, our study suggests that PCBs may be associated with fibroids in the absence of other gynecologic disorders such as endometriosis, but the associations varied by biologic media with more POPs emerging when quantified in fat. C1 [Trabert, Britton] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Chen, Zhen; Sun, Liping; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [Kannan, Kurunthachalam] SUNY Albany, Wadsworth Ctr, New York State Dept Hlth, Div Environm Hlth Sci, Albany, NY 12222 USA. [Kannan, Kurunthachalam] SUNY Albany, Dept Environm Hlth Sci, Albany, NY 12222 USA. [Peterson, C. Matthew] Univ Utah, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Salt Lake City, UT USA. [Pollack, Anna Z.] George Mason Univ, Coll Hlth & Human Serv, Dept Global & Community Hlth, Fairfax, VA 22030 USA. RP Trabert, B (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM britton.trabert@nih.gov RI Trabert, Britton/F-8051-2015; OI Pollack, Anna/0000-0002-4313-3298; Buck Louis, Germaine/0000-0002-1774-4490 FU Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health [NO1-DK-6-3428, NO1-DK-6-3427, 10001406-02] FX This work was funded in part by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (contracts NO1-DK-6-3428, NO1-DK-6-3427, 10001406-02 and 10001406-02). Ethicon Endo-Surgery, LLC, donated the HARMONIC ACE 36P shears and scalpel blades through a signed materials transfer agreement with the University of Utah and NICHD. NR 34 TC 3 Z9 3 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1559-0631 EI 1559-064X J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD MAY-JUN PY 2015 VL 25 IS 3 BP 278 EP 285 DI 10.1038/jes.2014.31 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA CG6JF UT WOS:000353405500007 PM 24802554 ER PT J AU Spaan, S Pronk, A Koch, HM Jusko, TA Jaddoe, VWV Shaw, PA Tiemeier, HM Hofman, A Pierik, FH Longnecker, MP AF Spaan, Suzanne Pronk, Anjoeka Koch, Holger M. Jusko, Todd A. Jaddoe, Vincent W. V. Shaw, Pamela A. Tiemeier, Henning M. Hofman, Albert Pierik, Frank H. Longnecker, Matthew P. TI Reliability of concentrations of organophosphate pesticide metabolites in serial urine specimens from pregnancy in the Generation R Study SO Journal of Exposure Science and Environmental Epidemiology LA English DT Article DE organophosphate pesticide metabolites; environmental exposure; variability; reliability; cohort study; epidemiologic studies ID DIALKYL PHOSPHATE METABOLITES; MEXICAN-AMERICAN CHILDREN; IN-UTERO; AGRICULTURAL COMMUNITY; EXPOSURE; ASSOCIATION; WOMEN; NEURODEVELOPMENT; CHLORPYRIFOS; POPULATION AB The widespread use of organophosphate (OP) pesticides has resulted in ubiquitous exposure in humans, primarily through their diet. Exposure to OP pesticides may have adverse health effects, including neurobehavioral deficits in children. The optimal design of new studies requires data on the reliability of urinary measures of exposure. In the present study, urinary concentrations of six dialkyl phosphate (DAP) metabolites, the main urinary metabolites of OP pesticides, were determined in 120 pregnant women participating in the Generation R Study in Rotterdam. Intra-class correlation coefficients (ICCs) across serial urine specimens taken at <18, 18-25, and >25 weeks of pregnancy were determined to assess reliability. Geometric mean total DAP metabolite concentrations were 229 (GSD 2.2), 240 (GSD 2.1), and 224 (GSD 2.2) nmol/g creatinine across the three periods of gestation. Metabolite concentrations from the serial urine specimens in general correlated moderately. The ICCs for the six DAP metabolites ranged from 0.14 to 0.38 (0.30 for total DAPs), indicating weak to moderate reliability. Although the DAP metabolite levels observed in this study are slightly higher and slightly more correlated than in previous studies, the low to moderate reliability indicates a high degree of within-person variability, which presents challenges for designing well-powered epidemiological studies. C1 [Spaan, Suzanne; Pronk, Anjoeka] TNO, Dept Risk Anal Prod Dev, NL-3700 AJ Zeist, Netherlands. [Koch, Holger M.] Ruhr Univ Bochum, Inst Prevent & Occupat Med German Social Accid In, Bochum, Germany. [Jusko, Todd A.] Univ Rochester, Sch Med & Dent, Dept Publ Hlth Sci, Rochester, NY USA. [Jusko, Todd A.] Univ Rochester, Sch Med & Dent, Dept Environm Med, Rochester, NY USA. [Jaddoe, Vincent W. V.; Tiemeier, Henning M.; Hofman, Albert] Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands. [Jaddoe, Vincent W. V.; Hofman, Albert] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Jaddoe, Vincent W. V.] Erasmus MC, Dept Pediat, Rotterdam, Netherlands. [Shaw, Pamela A.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA USA. [Tiemeier, Henning M.] Erasmus MC, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [Pierik, Frank H.] TNO, Dept Urban Environm & Safety, Utrecht, Netherlands. [Longnecker, Matthew P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC USA. RP Spaan, S (reprint author), TNO, Dept Risk Anal Prod Dev, Utrechtseweg 48,POB 360, NL-3700 AJ Zeist, Netherlands. EM suzanne.spaan@tno.nl RI Koch, Holger/B-3277-2011; OI Koch, Holger/0000-0002-8328-2837; Tiemeier, Henning/0000-0002-4395-1397; Longnecker, Matthew/0000-0001-6073-5322 FU Erasmus MC, Rotterdam; Erasmus University Rotterdam; Netherlands Organization for Health Research and Development (ZonMw); National Institutes of Health, National Institute of Environmental Health Sciences from the National Institutes of Health (NIH, USA) [K12 ES019852, P30 001247] FX The Generation R Study is conducted by the Erasmus MC, University Medical Center, Rotterdam, the Netherlands in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, the Rotterdam Homecare Foundation and the Stichting Trombose-dienst and Artsenlaboratorium Rijnmond (STAR), Rotterdam. We gratefully acknowledge the contribution of general practitioners, hospitals, midwives and pharmacies in Rotterdam. The first phase of the Generation R Study is made possible by financial support from the Erasmus MC, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development (ZonMw). We also thank Edwin van Wijngaarden for reviewing previous versions of the manuscript. This research received support from the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences and grants K12 ES019852 and P30 001247 from the National Institutes of Health (NIH, USA). We are grateful to R. Hauser of Harvard University for the suggestion to collect multiple urine specimens from subjects. NR 51 TC 4 Z9 4 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1559-0631 EI 1559-064X J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD MAY-JUN PY 2015 VL 25 IS 3 BP 286 EP 294 DI 10.1038/jes.2014.81 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA CG6JF UT WOS:000353405500008 PM 25515376 ER PT J AU Persky, S McBride, CM Faith, MS Wagner, LK Ward, DS AF Persky, Susan McBride, Colleen M. Faith, Myles S. Wagner, Laura K. Ward, Dianne S. TI Mothers' guilt responses to children's obesity risk feedback SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article DE family health history; guilt; obesity; parent; risk communication ID GENETIC INFORMATION; PREDICTING OBESITY; PARENTAL OBESITY; CHILDHOOD; INDIVIDUALS; OVERWEIGHT; BEHAVIORS; ADULTHOOD; FAMILIES AB This study explored the influence of family health history-based obesity risk feedback for their child on 147 overweight mothers' guilt related to children's lifestyle behaviors and passing down a genetic propensity for overweight. Mothers were randomized to receive, or not, obesity risk feedback for their 4- to 5-year-old child and then made food choices for them using a virtual reality-based buffet. Receipt of risk information increased lifestyle- and genetics-related guilt. Choosing fewer unhealthful foods for the child attenuated both types of guilt. Work in this area may aid in development of obesity risk feedback strategies that enhance child feeding. C1 [Persky, Susan; McBride, Colleen M.; Wagner, Laura K.] NHGRI, Bethesda, MD 20892 USA. [Faith, Myles S.; Ward, Dianne S.] Univ N Carolina, Chapel Hill, NC 27515 USA. RP Persky, S (reprint author), NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr,Rm B1B36, Bethesda, MD 20892 USA. EM perskys@mail.nih.gov FU Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 27 TC 0 Z9 0 U1 4 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1359-1053 EI 1461-7277 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD MAY PY 2015 VL 20 IS 5 SI SI BP 649 EP 658 DI 10.1177/1359105315576608 PG 10 WC Psychology, Clinical SC Psychology GA CG7FJ UT WOS:000353467700018 PM 25903251 ER PT J AU Davis, AS Chertow, DS Moyer, JE Suzich, J Sandouk, A Dorward, DW Logun, C Shelhamer, JH Taubenberger, JK AF Davis, A. Sally Chertow, Daniel S. Moyer, Jenna E. Suzich, Jon Sandouk, Aline Dorward, David W. Logun, Carolea Shelhamer, James H. Taubenberger, Jeffery K. TI Validation of Normal Human Bronchial Epithelial Cells as a Model for Influenza A Infections in Human Distal Trachea SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE confocal microscopy; electron microscopy; experimental pathology; immunohistochemistry; respiratory tract; viruses; viral diseases ID HUMAN AIRWAY EPITHELIUM; HUMAN RESPIRATORY-TRACT; RECEPTOR SPECIFICITY; VIRUS HEMAGGLUTININ; HUMAN LUNG; BINDING-SPECIFICITY; BETA-PROPIOLACTONE; SECRETORY PROTEIN; LIQUID INTERFACE; DERMAL MATRIX AB Primary normal human bronchial/tracheal epithelial (NHBE) cells, derived from the distal-most aspect of the trachea at the bifurcation, have been used for a number of studies in respiratory disease research. Differences between the source tissue and the differentiated primary cells may impact infection studies based on this model. Therefore, we examined how well-differentiated NHBE cells compared with their source tissue, the human distal trachea, as well as the ramifications of these differences on influenza A viral pathogenesis research using this model. We employed a histological analysis including morphological measurements, electron microscopy, multi-label immunofluorescence confocal microscopy, lectin histochemistry, and microarray expression analysis to compare differentiated NHBEs to human distal tracheal epithelium. Pseudostratified epithelial height, cell type variety and distribution varied significantly. Electron microscopy confirmed differences in cellular attachment and paracellular junctions. Influenza receptor lectin histochemistry revealed that 2,3 sialic acids were rarely present on the apical aspect of the differentiated NHBE cells, but were present in low numbers in the distal trachea. We bound fluorochrome bioconjugated virus to respiratory tissue and NHBE cells and infected NHBE cells with human influenza A viruses. Both indicated that the pattern of infection progression in these cells correlated with autopsy studies of fatal cases from the 2009 pandemic. C1 [Davis, A. Sally; Chertow, Daniel S.; Moyer, Jenna E.; Sandouk, Aline; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, NIH, Bethesda, MD 20892 USA. [Davis, A. Sally] Kansas State Univ, Coll Vet Med, Diagnost Med Pathobiol, Manhattan, KS 66506 USA. [Chertow, Daniel S.; Suzich, Jon; Logun, Carolea; Shelhamer, James H.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Dorward, David W.] NIAID, Electron Microscopy Unit, Res Technol Branch, Hamilton, MT USA. RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, NIH, 33 North Dr,MSC 3203, Bethesda, MD 20892 USA. EM taubenbergerj@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, National Institute of Health; NIH Comparative Molecular Pathology Research Training Program FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institute of Health. ASD and JKT are further thankful for the support of the NIH Comparative Molecular Pathology Research Training Program. NR 66 TC 7 Z9 7 U1 1 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 EI 1551-5044 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD MAY PY 2015 VL 63 IS 5 BP 312 EP 328 DI 10.1369/0022155415570968 PG 17 WC Cell Biology SC Cell Biology GA CG9KO UT WOS:000353634100002 PM 25604814 ER PT J AU Kim, SYH De Vries, R Parnami, S Wilson, R Kim, HM Frank, S Holloway, RG Kieburtz, K AF Kim, Scott Y. H. De Vries, Raymond Parnami, Sonali Wilson, Renee Kim, H. Myra Frank, Samuel Holloway, Robert G. Kieburtz, Karl TI Are therapeutic motivation and having one's own doctor as researcher sources of therapeutic misconception? SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID ADVANCED PARKINSONS-DISEASE; SHAM-SURGERY; CLINICAL-TRIALS; DOUBLE-BLIND; ONCOLOGY AB Background Desire for improvement in one's illness and having one's own doctor functioning as a researcher are thought to promote therapeutic misconception (TM), a phenomenon in which research subjects are said to conflate research with treatment. Purpose To examine whether subjects' therapeutic motivation and own doctor functioning as researcher are associated with TM. Methods We interviewed 90 persons with advanced Parkinson's disease (PD) enrolled or intending to enrol in sham surgery controlled neurosurgical trials, using qualitative interviews. Subjects were compared by motivation (primarily therapeutic vs primarily altruistic or dually motivated by altruistic and therapeutic motivation), and by doctor status (own doctor as site investigator vs not) on the following: understanding of purpose of study; understanding of research procedures; perception of chance of direct benefit; and recollection and perceptions concerning the risks. Results 60% had primarily therapeutic motivation and 44% had their own doctor as the site investigator, but neither were generally associated with increased TM responses. Overall level of understanding of purpose and procedures of research were high. Subjects responded with generally high estimates of probability of direct benefit, but their rationales were personal and complex. The therapeutic-motivation group was more sensitive to risks. Five (5.6%) subjects provided incorrect answers to the question about purpose of research, and yet, showed excellent understanding of research procedures. Conclusions In persons with PD involved in sham surgery clinical trials, being primarily motivated by desire for direct benefit to one's illness or having one's own doctor as the site investigator were not associated with greater TM responses. C1 [Kim, Scott Y. H.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Kim, Scott Y. H.; De Vries, Raymond; Parnami, Sonali] Univ Michigan, Ctr Bioeth & Social Sci Med, Ann Arbor, MI 48109 USA. [De Vries, Raymond] Univ Michigan, Dept Med Educ, Ann Arbor, MI 48109 USA. [Wilson, Renee; Kieburtz, Karl] Univ Rochester, Ctr Human Expt Therapeut, Rochester, NY USA. [Kim, H. Myra] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Frank, Samuel] Boston Univ, Dept Neurol, Boston, MA 02215 USA. [Holloway, Robert G.; Kieburtz, Karl] Univ Rochester, Dept Neurol, Rochester, NY USA. [Holloway, Robert G.] Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. [Kieburtz, Karl] Univ Rochester, Dept Environm Med, Rochester, NY USA. RP Kim, SYH (reprint author), NIH, Dept Bioeth, 10 Ctr Dr,1C118, Bethesda, MD 20892 USA. EM scott.kim@nih.gov FU National Institute for Neurological Disorders and Stroke [R01-NS062770]; CTSA award from the National Center for Research Resources [UL1 RR024160]; National Center for Advancing Translational Sciences of the National Institutes of Health FX This work was supported by the National Institute for Neurological Disorders and Stroke (R01-NS062770) and a CTSA award (UL1 RR024160) from the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health. NR 18 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 0306-6800 EI 1473-4257 J9 J MED ETHICS JI J. Med. Ethics PD MAY PY 2015 VL 41 IS 5 BP 391 EP 397 DI 10.1136/medethics-2013-101987 PG 7 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA CG6EL UT WOS:000353388900010 PM 24855070 ER PT J AU DeGrazia, D AF DeGrazia, David TI Creation ethics: reproduction, genetics and quality of life SO JOURNAL OF MEDICAL ETHICS LA English DT Editorial Material C1 NIH, Dept Bioeth, Bethesda, MD 20814 USA. RP DeGrazia, D (reprint author), NIH, Dept Bioeth, Bldg 10,Rm 1C118,10 Ctr Dr, Bethesda, MD 20814 USA. EM ddd@gwu.edu FU National Institutes of Health Clinical Center FX This work was supported, in part, by intramural funds from the National Institutes of Health Clinical Center. The views expressed are the author's own. They do not represent the position or policy of the National Institutes of Health, the US Public Health Service or the Department of Health and Human Services. NR 1 TC 0 Z9 0 U1 1 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 EI 1473-4257 J9 J MED ETHICS JI J. Med. Ethics PD MAY PY 2015 VL 41 IS 5 BP 415 EP 416 DI 10.1136/medethics-2013-101917 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA CG6EL UT WOS:000353388900015 PM 24368841 ER PT J AU DeGrazia, D AF DeGrazia, David TI A reply to critics of Creation Ethics SO JOURNAL OF MEDICAL ETHICS LA English DT Editorial Material C1 NIH, Dept Bioeth, Bethesda, MD 20814 USA. RP DeGrazia, D (reprint author), NIH, Dept Bioeth, Bldg 10,Rm 1C118,10 Ctr Dr, Bethesda, MD 20814 USA. EM ddd@gwu.edu FU National Institutes of Health Clinical Center FX This work was supported, in part, by intramural funds from the National Institutes of Health Clinical Center. The views expressed here are the author's own. They do not represent the position or policy of NIH, the US Public Health Service, or the Department of Health and Human Services. NR 4 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 EI 1473-4257 J9 J MED ETHICS JI J. Med. Ethics PD MAY PY 2015 VL 41 IS 5 BP 423 EP 424 DI 10.1136/medethics-2014-102531 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA CG6EL UT WOS:000353388900020 PM 25691666 ER PT J AU Li, LL Hamel, N Baker, K McGuffin, MJ Couillard, M Gologan, A Marcus, VA Chodirker, B Chudley, A Stefanovici, C Durandy, A Hegele, RA Feng, BJ Goldgar, DE Zhu, J De Rosa, M Gruber, SB Wimmer, K Young, B Chong, G Tischkowitz, MD Foulkes, WD AF Li, Lili Hamel, Nancy Baker, Kristi McGuffin, Michael J. Couillard, Martin Gologan, Adrian Marcus, Victoria A. Chodirker, Bernard Chudley, Albert Stefanovici, Camelia Durandy, Anne Hegele, Robert A. Feng, Bing-Jian Goldgar, David E. Zhu, Jun De Rosa, Marina Gruber, Stephen B. Wimmer, Katharina Young, Barbara Chong, George Tischkowitz, Marc D. Foulkes, William D. TI A homozygous PMS2 founder mutation with an attenuated constitutional mismatch repair deficiency phenotype SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID CANCER SYNDROME; GENE; DIAGNOSIS AB Background Inherited mutations in DNA mismatch repair genes predispose to different cancer syndromes depending on whether they are mono-allelic or bi-allelic. This supports a causal relationship between expression level in the germline and phenotype variation. As a model to study this relationship, our study aimed to define the pathogenic characteristics of a recurrent homozygous coding variant in PMS2 displaying an attenuated phenotype identified by clinical genetic testing in seven Inuit families from Northern Quebec. Methods Pathogenic characteristics of the PMS2 mutation NM_000535.5: c.2002A>G were studied using genotype-phenotype correlation, single-molecule expression detection and single genome microsatellite instability analysis. Results This PMS2 mutation generates a de novo splice site that competes with the authentic site. In homozygotes, expression of the full-length protein is reduced to a level barely detectable by conventional diagnostics. Median age at primary cancer diagnosis is 22 years among 13 NM_000535.5: c.2002A>G homozygotes, versus 8 years in individuals carrying biallelic truncating mutations. Residual expression of full-length PMS2 transcript was detected in normal tissues from homozygotes with cancers in their 20s. Conclusions Our genotype-phenotype study of c.2002A>G illustrates that an extremely low level of PMS2 expression likely delays cancer onset, a feature that could be exploited in cancer preventive intervention. C1 [Li, Lili; Hamel, Nancy; Couillard, Martin; Tischkowitz, Marc D.; Foulkes, William D.] McGill Univ, Dept Oncol, Program Canc Genet, Montreal, PQ H3T 1E2, Canada. [Li, Lili; Hamel, Nancy; Couillard, Martin; Tischkowitz, Marc D.; Foulkes, William D.] McGill Univ, Dept Human Genet, Program Canc Genet, Montreal, PQ H3T 1E2, Canada. [Li, Lili; Chong, George; Tischkowitz, Marc D.; Foulkes, William D.] McGill Univ, Dept Human Genet, Montreal, PQ H3T 1E2, Canada. [Hamel, Nancy; Foulkes, William D.] McGill Univ, Dept Med Genet, Ctr Hlth, Montreal, PQ H3T 1E2, Canada. [Baker, Kristi] McGill Univ, Dept Pathol, Montreal, PQ H3T 1E2, Canada. [Baker, Kristi] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [McGuffin, Michael J.] Ecole Technol Super, Dept Software & Informat Technol Engn, Montreal, PQ, Canada. [Couillard, Martin; Tischkowitz, Marc D.; Foulkes, William D.] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. [Gologan, Adrian; Chong, George] McGill Univ, Jewish Gen Hosp, Dept Pathol, Montreal, PQ H3T 1E2, Canada. [Marcus, Victoria A.] McGill Univ, Ctr Hlth, Dept Pathol, Montreal, PQ H3T 1E2, Canada. [Chodirker, Bernard; Chudley, Albert] Univ Manitoba, Dept Pediat & Child Hlth, Winnipeg, MB R3T 2N2, Canada. [Chodirker, Bernard; Chudley, Albert] Dept Biochem & Med Genet, Winnipeg, MB, Canada. [Stefanovici, Camelia] Univ Manitoba, Fac Med, Dept Pathol, Winnipeg, MB, Canada. [Durandy, Anne] Hop Necker Enfants Malad, INSERM, U768, Paris, France. [Hegele, Robert A.] Univ Western Ontario, Robarts Res Inst, London, ON, Canada. [Hegele, Robert A.] Univ Western Ontario, Schulich Sch Med & Dent, London, ON, Canada. [Feng, Bing-Jian; Goldgar, David E.] Univ Utah, Hlth Sci Ctr, Dept Dermatol, Salt Lake City, UT USA. [Zhu, Jun] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [De Rosa, Marina] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy. [De Rosa, Marina] Univ Naples Federico II, CEINGE Biotechnol Avanzate, Naples, Italy. [Gruber, Stephen B.] Univ So Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Wimmer, Katharina] Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Human Genet, A-6020 Innsbruck, Austria. [Young, Barbara] McGill Univ, Ctr Hlth, Dept Med, Montreal, PQ H3T 1E2, Canada. [Young, Barbara] Hlth Canada Quebec Reg, Nations & Inuit Hlth Branch 1, Montreal, PQ, Canada. [Tischkowitz, Marc D.] Univ Cambridge, Dept Med Genet, Cambridge, England. RP Foulkes, WD (reprint author), McGill Univ, Jewish Gen Hosp, Lady Davis Inst, 3755 Cote Ste Catherine Rd, Montreal, PQ H3T 1E2, Canada. EM william.foulkes@mcgill.ca RI Hegele, Robert/G-3301-2011; OI Baker, Kristi/0000-0002-2993-3889; foulkes, william/0000-0001-7427-4651 FU Canadian Gene Cure Foundation; Canadian Cancer Society Research Institute [700252]; Systems Biology Training Program by Canadian Institute of Health Research FX This work was supported by grants from the Canadian Gene Cure Foundation and the Canadian Cancer Society Research Institute (grant # 700252). LL received fellowship funding from the Systems Biology Training Program by the Canadian Institute of Health Research. NR 18 TC 3 Z9 3 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 EI 1468-6244 J9 J MED GENET JI J. Med. Genet. PD MAY PY 2015 VL 52 IS 5 BP 348 EP 352 DI 10.1136/jmedgenet-2014-102934 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA CG1NX UT WOS:000353041000009 PM 25691505 ER PT J AU Chittiboina, P Heiss, JD Lonser, RR AF Chittiboina, Prashant Heiss, John D. Lonser, Russell R. TI Accuracy of direct magnetic resonance imaging-guided placement of drug infusion cannulae SO JOURNAL OF NEUROSURGERY LA English DT Article DE accuracy; convection-enhanced delivery; brainstem glioma; gadolinium; magnetic resonance imaging; targeting; surgical technique ID CONVECTION-ENHANCED DELIVERY; GLIOBLASTOMA; BRAIN; TRIAL; MRI AB An intraoperative MRI (iMRI)-compatible system has been developed for direct placement of convection-enhanced delivery (CED) cannulae using real-time imaging. To establish the precision and feasibility of this technology, the authors analyzed findings in patients who underwent direct iMRI CED cannula placement. Three consecutive patients underwent iMRI-guided placement of CED infusion cannulae (6 cannulae) for treatment of diffuse intrinsic brainstem glioma (2 patients) or Parkinson's disease (1 patient). Convective infusion cannulae were guided to the target using the ClearPoint iMRI-based navigation platform (MRI Interventions, Inc.). Placement accuracy was analyzed. Real-time iMRI during infusion cannula insertion allowed for monitoring of trajectory accuracy during placement. During cannula insertion, no reinsertions or changes due to errors in targeting were necessary. The mean radial error was 1.0 +/- 0.5 mm (+/- SD). There was no correlation between the total length of the planned trajectory and the radial error (Pearson's coefficient: -0.40; p = 0.5). The mean anteroposterior and lateral errors were 0.9 +/- 0.5 and 0.3 +/- 0.2 mm, respectively. The mean in-plane distance error was 1.0 +/- 0.4 mm. The mean tip error (scalar distance between the planned target and actual tip) was 1.9 +/- 0.9 mm. There was no correlation between the length of the planned trajectory and any of the measured errors. No complications were associated with cannula placement. Real-time iMRI-based targeting and monitoring of infusion cannula placement is a safe, effective, and accurate technique that should enable more selective perfusion of brain regions. C1 [Chittiboina, Prashant; Heiss, John D.; Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Lonser, Russell R.] Ohio State Univ, Wexner Med Ctr, Dept Neurol Surg, Columbus, OH 43210 USA. RP Lonser, RR (reprint author), Ohio State Univ, Wexner Med Ctr, Dept Neurol Surg, 410 W 10th Ave,N1047 Doan Hall, Columbus, OH 43210 USA. EM russell.lonser@osumc.edu OI Heiss, John/0000-0002-3890-0165 FU National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health FX This study was funded by the intramural research program of the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health. IL13-PE was provided by InSys Therapeutics, Inc., under a cooperative research and development agreement with NINDS. The Smart Flow cannula and Clear Point system were provided by MRI Interventions, Inc., under a clinical trial agreement with NINDS. NR 19 TC 5 Z9 5 U1 0 U2 9 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 2015 VL 122 IS 5 BP 1173 EP 1179 DI 10.3171/2014.11.JNS131888 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CG5XP UT WOS:000353369500027 PM 25594325 ER PT J AU Lukas, VA Fishbein, KW Lin, PC Schar, M Schneider, E Neu, CP Spencer, RG Reiter, DA AF Lukas, Vanessa A. Fishbein, Kenneth W. Lin, Ping-Chang Schaer, Michael Schneider, Erika Neu, Corey P. Spencer, Richard G. Reiter, David A. TI Classification of Histologically Scored Human Knee Osteochondral Plugs by Quantitative Analysis of Magnetic Resonance Images at 3T SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE osteoarthritis; imaging; cartilage matrix; quantitative MRI; classification ID OSTEOARTHRITIS CARTILAGE HISTOPATHOLOGY; SUPERFICIAL ZONE PROTEIN; ARTICULAR-CARTILAGE; IN-VIVO; TIBIOFEMORAL JOINT; HYALINE CARTILAGE; RELAXATION-TIMES; T-2 RELAXATION; MRI; T2 AB This work evaluates the ability of quantitative MRI to discriminate between normal and pathological human osteochondral plugs characterized by the Osteoarthritis Research Society International (OARSI) histological system. Normal and osteoarthritic human osteochondral plugs were scored using the OARSI histological system and imaged at 3 T using MRI sequences producing T1 and T2 contrast and measuring T-1, T-2, and T-2* relaxation times, magnetization transfer, and diffusion. The classification accuracies of quantitative MRI parameters and corresponding weighted image intensities were evaluated. Classification models based on the Mahalanobis distance metric for each MRI measurement were trained and validated using leave-one-out cross-validation with plugs grouped according to OARSI histological grade and score. MRI measurements used for classification were performed using a region-of-interest analysis which included superficial, deep, and full-thickness cartilage. The best classifiers based on OARSI grade and score were T-1- and T-2-weighted image intensities, which yielded accuracies of 0.68 and 0.75, respectively. Classification accuracies using OARSI score-based group membership were generally higher when compared with grade-based group membership. MRI-based classificationeither using quantitative MRI parameters or weighted image intensitiesis able to detect early osteoarthritic tissue changes as classified by the OARSI histological system. These findings suggest the benefit of incorporating quantitative MRI acquisitions in a comprehensive clinical evaluation of OA. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:640-650, 2015. C1 [Lukas, Vanessa A.; Fishbein, Kenneth W.; Spencer, Richard G.; Reiter, David A.] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA. [Lin, Ping-Chang] Howard Univ, Coll Med, Dept Radiol, Washington, DC USA. [Schaer, Michael] Philips Healthcare, Highland Hts, OH USA. [Schneider, Erika] Cleveland Clin Fdn, Imaging Inst, Cleveland, OH 44195 USA. [Neu, Corey P.] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA. RP Reiter, DA (reprint author), NIA, Lab Clin Invest, NIH, 3001 S Hanover St, Baltimore, MD 21224 USA. EM reiterda@mail.nih.gov RI Lin, Ping-Chang/C-9811-2009; OI Lin, Ping-Chang/0000-0003-0918-4072; Schar, Michael/0000-0002-7044-9941; Fishbein, Kenneth/0000-0002-6353-4603 FU National Institutes of Health; National Institute on Aging; NIH [R01 AR063712] FX Grant sponsor: Intramural Research Program of the National Institutes of Health; Grant sponsor: National Institute on Aging; Grant sponsor: NIH; Grant number: R01 AR063712. NR 53 TC 3 Z9 3 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD MAY PY 2015 VL 33 IS 5 BP 640 EP 650 DI 10.1002/jor.22810 PG 11 WC Orthopedics SC Orthopedics GA CG6NB UT WOS:000353417300005 PM 25641500 ER PT J AU Coelho, SG Valencia, JC Yin, LL Smuda, C Mahns, A Kolbe, L Miller, SA Beer, JZ Zhang, GF Tuma, PL Hearing, VJ AF Coelho, Sergio G. Valencia, Julio C. Yin, Lanlan Smuda, Christoph Mahns, Andre Kolbe, Ludger Miller, Sharon A. Beer, Janusz Z. Zhang, Guofeng Tuma, Pamela L. Hearing, Vincent J. TI UV exposure modulates hemidesmosome plasticity, contributing to long-term pigmentation in human skin SO JOURNAL OF PATHOLOGY LA English DT Article DE hemidesmosome; skin; pigmentation; ultraviolet radiation; sunburn ID ULTRAVIOLET-RADIATION; HUMAN KERATINOCYTES; SOX PROTEINS; IN-SITU; MELANOMA; DIFFERENTIATION; ASSOCIATION; GENE; DNA; PROLIFERATION AB Human skin colour, ie pigmentation, differs widely among individuals, as do their responses to various types of ultraviolet radiation (UV) and their risks of skin cancer. In some individuals, UV-induced pigmentation persists for months to years in a phenomenon termed long-lasting pigmentation (LLP). It is unclear whether LLP is an indicator of potential risk for skin cancer. LLP seems to have similar features to other forms of hyperpigmentation, eg solar lentigines or age spots, which are clinical markers of photodamage and risk factors for precancerous lesions. To investigate what UV-induced molecular changes may persist in individuals with LLP, clinical specimens from non-sunburn-inducing repeated UV exposures (UVA, UVB or UVA + UVB) at 4 months post-exposure (short-term LLP) were evaluated by microarray analysis and dataset mining. Validated targets were further evaluated in clinical specimens from six healthy individuals (three LLP+ and three LLP-) followed for more than 9 months (long-term LLP) who initially received a single sunburn-inducing UVA + UVB exposure. The results support a UV-induced hyperpigmentation model in which basal keratinocytes have an impaired ability to remove melanin that leads to a compensatory mechanism by neighbouring keratinocytes with increased proliferative capacity to maintain skin homeostasis. The attenuated expression of SOX7 and other hemidesmosomal components (integrin 64 and plectin) leads to increased melanosome uptake by keratinocytes and points to a spatial regulation within the epidermis. The reduced density of hemidesmosomes provides supporting evidence for plasticity at the epidermal-dermal junction. Altered hemidesmosome plasticity, and the sustained nature of LLP, may be mediated by the role of SOX7 in basal keratinocytes. The long-term sustained subtle changes detected are modest, but sufficient to create dramatic visual differences in skin colour. These results suggest that the hyperpigmentation phenomenon leading to increased interdigitation develops in order to maintain normal skin homeostasis in individuals with LLP. Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Coelho, Sergio G.; Valencia, Julio C.; Yin, Lanlan; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Smuda, Christoph; Mahns, Andre; Kolbe, Ludger] Beiersdorf AG, R&D Skin Res, Hamburg, Germany. [Miller, Sharon A.; Beer, Janusz Z.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Zhang, Guofeng] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Tuma, Pamela L.] Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. RP Coelho, SG (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 2132, Bethesda, MD 20892 USA. EM sergio.coelho@fda.hhs.gov FU Office of Science; Center for Devices and Radiological Health, Food and Drug Administration; National Cancer Institute, National Institutes of Health FX This research was supported in part by the Office of Science and the Center for Devices and Radiological Health, Food and Drug Administration, and in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. We would like to acknowledge Professors Ito and Wakamatsu for completing the melanosome melanin analysis. NR 39 TC 4 Z9 4 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3417 EI 1096-9896 J9 J PATHOL JI J. Pathol. PD MAY PY 2015 VL 236 IS 1 BP 17 EP 29 DI 10.1002/path.4497 PG 13 WC Oncology; Pathology SC Oncology; Pathology GA CG1OF UT WOS:000353041900003 PM 25488118 ER PT J AU Akshintala, S Avery, RA Murnick, J Verdun, N Diab, Y AF Akshintala, Srivandana Avery, Robert A. Murnick, Jonathan Verdun, Nicole Diab, Yaser TI Isolated Midbrain Ischemic Infarct in Association With Hyperlipoproteinemia (a): A Report of 2 Adolescent Patients SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE thrombophilia; acute ischemic stroke; hyperlipoproteinemia (a); midbrain; adolescent ID RISK-FACTORS; PEDIATRIC STROKE; CHILDHOOD; LIPOPROTEIN; CHILDREN AB Arterial ischemic strokes (AIS) localized solely to the midbrain are extremely uncommon in the pediatric population. Elevated lipoprotein (a), which promotes atherosclerosis and a prothrombotic state, has been associated with increased risk of AIS in children and adults. Here we describe a 17-year-old boy and a 15-year-old girl who presented with internuclear ophthalmoplegia secondary to an isolated midbrain AIS. Evaluation for risk factors for AIS in these otherwise healthy adolescents identified hyperlipoproteinemia (a) in combination with other potential prothrombotic conditions suggesting that hypercoagulable states such as hyperlipoproteinemia (a) may have contributed to development of small-vessel arteriopathy and localized AIS. C1 [Akshintala, Srivandana; Verdun, Nicole; Diab, Yaser] Childrens Natl Med Ctr, Dept Hematol, Washington, DC 20010 USA. [Avery, Robert A.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Murnick, Jonathan] Childrens Natl Med Ctr, Dept Diagnost Imaging & Radiol, Washington, DC 20010 USA. RP Akshintala, S (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr,Bldg 10 CRC,Room 1-5750,MSC 1101, Bethesda, MD 20892 USA. EM akshintalas@mail.nih.gov OI Avery, Robert/0000-0003-1453-7282 NR 16 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1077-4114 EI 1536-3678 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD MAY PY 2015 VL 37 IS 4 BP 315 EP 318 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CG5AR UT WOS:000353301600032 PM 25739027 ER PT J AU Katarkar, A Saha, A Mukherjee, S Kundu, D Bandyopadhyay, P Chaudhuri, K AF Katarkar, Atul Saha, Arindam Mukherjee, Sanjit Kundu, Debabrata Bandyopadhyay, Prasanta Chaudhuri, Keya TI Telomerase Expression in Individuals With Chronic and Aggressive Periodontitis SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Aggressive periodontitis; chronic periodontitis; gingival crevicular fluid; gingival recession; periodontal attachment loss; telomerase ID GINGIVAL CREVICULAR FLUID; REVERSE-TRANSCRIPTASE HTERT; MESSENGER-RNA EXPRESSION; CATALYTIC SUBUNIT; GENE-EXPRESSION; UP-REGULATION; HUMAN CANCER; CELLS; ACTIVATION; DISEASES AB Background: The aim of this study is to evaluate the expression of human telomerase reverse transcription (hTERT) enzyme in chronic periodontitis (CP) and aggressive periodontitis (AgP) compared with healthy individuals. Methods: A total of 79 individuals consented to participate in the study. The study sample comprised healthy individuals (n = 30), patients with CP (n = 30), and patients with AgP (n = 19). Gingival tissue was collected and evaluated for hTERT expression by Western blot and immunohistochemical methods. Reverse transcription polymerase chain reaction was performed using the gingival crevicular fluid (GCF) samples. Results: The hTERT messenger RNA (mRNA) and protein expression was significantly higher in AgP compared with CP (P < 0.001). In GCF, 53.33% of patients with CP and 68.42% of patients with AgP were showing hTERT mRNA expression, but it was not detected in the control group. The AgP tissue showed higher hTERT expression compared with CP (P < 0.001). The hTERT mRNA expression did not show a correlation with gingival index (GI), plaque index (PI), probing depth (PD), and clinical attachment loss (AL) in patients with AgP, whereas hTERT protein expression was strongly correlated with GI, PI, PD, and AL in patients with AgP. The protein expression of hTERT shows significant but moderate correlation with GI and AL in patients with CP. Conclusion: High expression of hTERT might be associated with periodontal disease progression, suggesting that hTERT could be a potential prognostic marker. C1 [Katarkar, Atul; Mukherjee, Sanjit; Chaudhuri, Keya] Indian Inst Chem Biol, CSIR, Mol & Human Genet Div, Kolkata 700032, India. [Saha, Arindam; Kundu, Debabrata; Bandyopadhyay, Prasanta] Dr R Ahmed Dent Coll & Hosp, Dept Periodont, Kolkata, India. [Mukherjee, Sanjit] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Chaudhuri, K (reprint author), Indian Inst Chem Biol, CSIR, Mol & Human Genet Div, 4 Raja SC Mullick Rd, Kolkata 700032, India. EM kchaudhuri@iicb.res.in OI MUKHERJEE, SANJIT/0000-0002-3295-9668 FU Council of Scientific and Industrial Research Grant [21(0932)/12/EMR-II]; Indian Council of Medical Research FX This study is supported by the Council of Scientific and Industrial Research Grant 21(0932)/12/EMR-II. Drs. Katarkar and Saha contributed equally to this work. Dr. Katarkar is grateful to the Indian Council of Medical Research for providing a senior research fellowship. The authors report no conflicts of interest related to this study. NR 50 TC 1 Z9 1 U1 2 U2 6 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 EI 1943-3670 J9 J PERIODONTOL JI J. Periodont. PD MAY PY 2015 VL 86 IS 5 BP 656 EP 665 DI 10.1902/jop.2015.140540 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CG6LE UT WOS:000353411400009 PM 25660499 ER PT J AU Daikoku, E Saito, M Ono, F AF Daikoku, Eriko Saito, Masahisa Ono, Fumihito TI Zebrafish mutants of the neuromuscular junction: swimming in the gene pool SO Journal of Physiological Sciences LA English DT Review DE Synapse; Zebrafish; Acetylcholine receptor; Mutant ID MUSCLE ACETYLCHOLINE-RECEPTOR; IN-VIVO; MYASTHENIC SYNDROME; RAPSYN CLUSTERS; BETA-SUBUNIT; IDENTIFICATION; SYNAPSES; PROTEIN; REVEALS; SLOW AB This review provides an overview of zebrafish mutants with dysfunctional acetylcholine receptors or related proteins at the neuromuscular junction (NMJ). The NMJ, which has served as the classical model of the chemical synapse, uses acetylcholine as the neurotransmitter, and mutations of proteins involved in the signaling cascade lead to a variety of behavioral phenotypes. Mutants isolated after random chemical mutagenesis screening are summarized, and advances in the field resulting from these mutants are discussed. C1 [Daikoku, Eriko; Saito, Masahisa; Ono, Fumihito] Osaka Med Coll, Dept Physiol, Takatsuki, Osaka 5698686, Japan. [Ono, Fumihito] NIAAA, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. RP Ono, F (reprint author), Osaka Med Coll, Dept Physiol, Takatsuki, Osaka 5698686, Japan. EM onof@art.osaka-med.ac.jp FU intramural program at NIAAA FX We thank Dr Henry Puhl for critical reading of the manuscript. We thank Ms Kasumi Minamimoto and Ms Chika Murakami for their help with preparation of the figures. This work was supported by the intramural program at NIAAA. NR 43 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 1880-6546 EI 1880-6562 J9 J PHYSIOL SCI JI J. Physiol. Sci. PD MAY PY 2015 VL 65 IS 3 BP 217 EP 221 DI 10.1007/s12576-015-0372-9 PG 5 WC Physiology SC Physiology GA CG6LB UT WOS:000353411100002 PM 25782439 ER PT J AU Harlan, LC Eisenstein, J Russell, MC Stevens, JL Cardona, K AF Harlan, Linda C. Eisenstein, Jana Russell, Maria C. Stevens, Jennifer L. Cardona, Kenneth TI Gastrointestinal Stromal Tumors: Treatment Patterns of a Population-Based Sample SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE SEER registry; sarcoma; imatinib; GIST ID ADJUVANT THERAPY; MANAGEMENT; PATHOLOGY; PROGNOSIS; MUTATIONS; DIAGNOSIS; STOMACH; KIT AB ObjectivesThe National Cancer Institute (NCI) annually confirms therapy with treating physicians on a sample of patients diagnosed with a specific cancer. MethodsUsing the NCI Patterns of Care data, treatment patterns were examined on a population-based sample of patients diagnosed with gastrointestinal stromal tumors (GIST) in 2008. ResultsA random sample of 323 of 405 GIST patients registered in SEER was selected. Most patients had gastric GISTs, were 65years, white, had private insurance, and treated in a hospital with a residency program. Surgery was primarily performed in patients with non-metastatic disease (94%), in which: 26, 12, and 36% were at low, intermediate, and high-risk of recurrence, respectively. Amongst low-risk patients, approximate to 30% received adjuvant therapy. Amongst patients at higher risk, 26-40% did not receive adjuvant therapy. Imatinib was the most common targeted therapy administered. On multivariate analysis, age and risk-group were associated with receipt of adjuvant targeted therapy. ConclusionsOur study shows that in 2008, the majority of patients diagnosed with GIST received appropriate surgical and adjuvant therapies. However, a considerable subset may have been overtreated and undertreated. Future studies identifying factors that impact the delivery of adjuvant therapy should be conducted. J. Surg. Oncol. 2015 111:702-707. (c) 2015 Wiley Periodicals, Inc. C1 [Harlan, Linda C.; Eisenstein, Jana] NCI, ARP, Bethesda, MD 20892 USA. [Russell, Maria C.; Cardona, Kenneth] Emory Univ, Winship Canc Inst, Dept Surg, Div Surg Oncol, Atlanta, GA 30322 USA. [Stevens, Jennifer L.] Informat Management Serv Inc, Silver Spring, MD USA. RP Harlan, LC (reprint author), NCI, ARP, 9609 Med Ctr Dr,MSC 9762,Room 3E426, Bethesda, MD 20892 USA. EM lh50w@nih.gov FU National Cancer Institute [HHSN261201000024C, HSN261201000025C, HHSN261201000032C, HHSN261201000027C, HHSN261201000026C, HHSN261201000140C, HHSN261201000037C, HHSN261201000033C, HHSN261201000034C, HHSN261201000035C, HHSN261201000029C, HHSN261201000031C, HHSN261201000028C, HHSN261201000030C] FX Grant sponsor: National Cancer Institute contracts; Grant numbers: HHSN261201000024C, HSN261201000025C, HHSN261201000032C, HHSN261201000027C, HHSN261201000026C, HHSN261201000140C, HHSN261201000037C, HHSN261201000033C, HHSN261201000034C, HHSN261201000035C, HHSN261201000029C, HHSN261201000031C, HHSN261201000028C, HHSN261201000030C. NR 20 TC 2 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD MAY 1 PY 2015 VL 111 IS 6 BP 702 EP 707 DI 10.1002/jso.23879 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA CG6ND UT WOS:000353417700007 PM 25900896 ER PT J AU Teranishi, Y Matsubara, T Krausz, KW Le, TTT Gonzalez, FJ Yoshizato, K Ikeda, K Kawada, N AF Teranishi, Yuga Matsubara, Tsutomu Krausz, Kristopher W. Le, Thi T. T. Gonzalez, Frank J. Yoshizato, Katsutoshi Ikeda, Kazuo Kawada, Norifumi TI Involvement of hepatic stellate cell cytoglobin in acute hepatocyte damage through the regulation of CYP2E1-mediated xenobiotic metabolism SO LABORATORY INVESTIGATION LA English DT Article ID LIVER-INJURY; ACETAMINOPHEN; HYPOXIA; MICE; ACTIVATION; RAT; MICROCIRCULATION; REGENERATION; NEUROGLOBIN; PROTEIN AB Oxygen (O-2) is required for cytochrome P450 (CYP)-dependent drug metabolism. Cytoglobin (CYGB) is a unique globin expressed exclusively in hepatic stellate cells (HSCs). However, its role in O-2-dependent metabolism in neighboring hepatocytes remains unknown. This study provides evidence that CYGB in HSCs is involved in acetaminophen (N-acetyl-p-aminophenol; APAP)-induced hepatotoxicity. Serum alanine aminotransferase levels were higher in wild-type mice than in Cygb-null mice. Wild-type mice exhibited more severe hepatocyte necrosis around the central vein area compared with Cygb-null mice, thus indicating that CYGB deficiency protects against APAP-induced liver damage. Although no difference in the hepatic expression of CYP2E1, a key enzyme involved in APAP toxicity, was observed between wild-type and Cygb-null mice, the serum levels of the APAP metabolites cysteinyl-APAP and N-acetyl-cysteinyl-APAP were decreased in Cygb-null mice, suggesting reduced APAP metabolism in the livers of Cygb-null mice. In primary cultures, APAP-induced hepatocyte damage was increased by co-culturing with wild-type HSCs but not with Cygb-null HSCs. In addition, cell damage was markedly alleviated under low O-2 condition (5% O2), suggesting the requirement of O-2 for APAP toxicity. Carbon tetrachloride-induced liver injury (CYP2E1-dependent), but not lipopolysaccharide/ D-galactosamine-induced injury (CYP2E1-independent), was similarly alleviated in Cygb-null mice. Considering the function of CYGB as O-2 carrier, these results strongly support the hypothesis that HSCs are involved in the CYP2E1-mediated xenobiotic activation by augmenting O-2 supply to hepatocytes. In conclusion, CYGB in HSCs contributes to the CYP-mediated metabolism of xenobiotics in hepatocytes by supplying O-2 for enzymatic oxidation. C1 [Teranishi, Yuga; Le, Thi T. T.; Yoshizato, Katsutoshi; Kawada, Norifumi] Osaka City Univ, Grad Sch Med, Dept Hepatol, Osaka 5458585, Japan. [Matsubara, Tsutomu; Ikeda, Kazuo] Osaka City Univ, Grad Sch Med, Dept Anat & Regenerat Biol, Osaka 5458585, Japan. [Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Yoshizato, Katsutoshi] Phoenixbio Co Ltd, Hiroshima, Japan. RP Kawada, N (reprint author), Osaka City Univ, Grad Sch Med, Dept Hepatol, Abeno Ku, 1-4-3 Asahimachi, Osaka 5458585, Japan. EM kawadanori@med.osaka-cu.ac.jp FU Japan Society for the Promotion of Science (JSPS) [25293177, 20132016]; Mochida Memorial Foundation; National Cancer Institute Intramural Research Program FX We thank Ms Chiho Kadono for animal care, and Dr Wenhao Cui, Dr Keiko Iwaisako, and Dr Kazuki Nakatani (Osaka City University) for their valuable discussion and comments on this study. This investigation was supported in part by a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science (JSPS) through grant 25293177 (to NK) (20132016), the Mochida Memorial Foundation (to TM), and the National Cancer Institute Intramural Research Program (to FJG). NR 27 TC 4 Z9 4 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD MAY PY 2015 VL 95 IS 5 BP 515 EP 524 DI 10.1038/labinvest.2015.29 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA CG8SR UT WOS:000353583300006 PM 25686096 ER PT J AU Hayashi, PH Barnhart, HX Fontana, RJ Chalasani, N Davern, TJ Talwalkar, JA Reddy, KR Stolz, AA Hoofnagle, JH Rockey, DC AF Hayashi, Paul H. Barnhart, Huiman X. Fontana, Robert J. Chalasani, Naga Davern, Timothy J. Talwalkar, Jayant A. Reddy, K. Rajender Stolz, Andrew A. Hoofnagle, Jay H. Rockey, Don C. TI Reliability of causality assessment for drug, herbal and dietary supplement hepatotoxicity in the Drug-Induced Liver Injury Network (DILIN) SO LIVER INTERNATIONAL LA English DT Article DE adverse reaction; diagnosis; drug-induced liver injury; hepatotoxicity; toxicity ID ADVERSE REACTIONS; HEPATITIS; VALIDATION; DIAGNOSIS; DESIGN AB Background & AimsBecause of the lack of objective tests to diagnose drug-induced liver injury (DILI), causality assessment is a matter of debate. Expert opinion is often used in research and industry, but its test-retest reliability is unknown. To determine the test-retest reliability of the expert opinion process used by the Drug-Induced Liver Injury Network (DILIN). MethodsThree DILIN hepatologists adjudicate suspected hepatotoxicity cases to one of five categories representing levels of likelihood of DILI. Adjudication is based on retrospective assessment of gathered case data that include prospective follow-up information. One hundred randomly selected DILIN cases were re-assessed using the same processes for initial assessment but by three different reviewers in 92% of cases. ResultsThe median time between assessments was 938days (range 140-2352). Thirty-one cases involved >1 agent. Weighted kappa statistics for overall case and individual agent category agreement were 0.60 (95% CI: 0.50-0.71) and 0.60 (0.52-0.68) respectively. Overall case adjudications were within one category of each other 93% of the time, while 5% differed by two categories and 2% differed by three categories. Fourteen per cent crossed the 50% threshold of likelihood owing to competing diagnoses or atypical timing between drug exposure and injury. ConclusionsThe DILIN expert opinion causality assessment method has moderate interobserver reliability but very good agreement within one category. A small but important proportion of cases could not be reliably diagnosed as 50% likely to be DILI. C1 [Hayashi, Paul H.] Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Barnhart, Huiman X.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Barnhart, Huiman X.] Duke Univ, Dept Biostat, Durham, NC USA. [Fontana, Robert J.] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Chalasani, Naga] Indiana Univ Sch Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA. [Davern, Timothy J.] Calif Pacific Med Ctr, Div Gastroenterol, San Francisco, CA USA. [Talwalkar, Jayant A.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. [Reddy, K. Rajender] Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. [Stolz, Andrew A.] Univ So Calif, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA. [Hoofnagle, Jay H.] NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. [Rockey, Don C.] Univ Texas Southwestern, Div Gastroenterol, Dallas, TX USA. RP Hayashi, PH (reprint author), UNC Liver Program, Div Gastroenterol & Hepatol, CB 7584 Burnett Womack Bldg,Room 8011, Chapel Hill, NC 27599 USA. EM paul_hayashi@med.unc.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [2U01-DK065176-06, 2U01-DK065201-06, 2U01-DK065184-06, 2U01-DK065211-06, 5U01DK065 193-04, 5U01-DK065238-08, 1U01-DK083023-01, 1U01-DK083027-01, 1U01-DK082992-01, 1U01-DK083020-01]; CTSA [UL1 RR025761, UL1 RR025747, UL1 RR024134, UL1 RR024986, UL1 RR024982, UL1 RR024150]; Intramural Research Program of the NIH, National Cancer Institute FX The DILIN Network is structured as a U01 cooperative agreement with funds provided by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under grants: 2U01-DK065176-06 (Duke), 2U01-DK065201-06 (UNC), 2U01-DK065184-06 (Michigan), 2U01-DK065211-06 (Indiana), 5U01DK065 193-04 (UConn), 5U01-DK065238-08 (UCSF/CPMC), 1U01-DK083023-01 (UTSW), 1U01-DK083027-01 (TJH/UPenn), 1U01-DK082992-01 (Mayo), 1U01-DK083020-01 (USC). Additional funding is provided by CTSA grants: UL1 RR025761 (Indiana), UL1 RR025747 (UNC), UL1 RR024134 (UPenn), UL1 RR024986 (Michigan), UL1 RR024982 (UTSW), UL1 RR024150 (Mayo) and in part by the Intramural Research Program of the NIH, National Cancer Institute. NR 20 TC 10 Z9 10 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1478-3223 EI 1478-3231 J9 LIVER INT JI Liver Int. PD MAY PY 2015 VL 35 IS 5 BP 1623 EP 1632 DI 10.1111/liv.12540 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CG9OM UT WOS:000353645900018 PM 24661785 ER PT J AU Habermann, N Makar, KW Abbenhardt, C Xiao, LR Wang, CY Utsugi, HK Alfano, CM Campbell, KL Duggan, C Foster-Schubert, KE Mason, CE Imayama, I Blackburn, GL Potter, JD Mctiernan, A Ulrich, CM AF Habermann, Nina Makar, Karen W. Abbenhardt, Clare Xiao, Liren Wang, Ching-Yun Utsugi, Heidi K. Alfano, Catherine M. Campbell, Kristin L. Duggan, Catherine Foster-Schubert, Karen E. Mason, Caitlin E. Imayama, Ikuyo Blackburn, George L. Potter, John D. Mctiernan, Anne Ulrich, Cornelia M. TI No Effect of Caloric Restriction or Exercise on Radiation Repair Capacity SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE DNA REPAIR; COMET ASSAY; RANDOMIZED CONTROLLED TRIAL; EXERCISE; CALORIC RESTRICTION; WOMEN ID OXIDATIVE DNA-DAMAGE; ALKALINE COMET ASSAY; WEIGHT-LOSS; BREAST-CANCER; POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; SKELETAL-MUSCLE; STRESS; INTERVENTION; LYMPHOCYTES AB Introduction: Maintenance of normal weight and higher levels of physical activity are associated with a reduced risk of several types of cancer. Because genomic instability is regarded as a hallmark of cancer development, one proposed mechanism is improvement of DNA repair function. We investigated links between dietary weight loss, exercise, and strand break rejoining in an ancillary study to a randomized-controlled trial. Methods: Overweight/obese postmenopausal women (n = 439) were randomized to the following: a) reduced calorie weight loss diet ("diet,'' n = 118), b) moderate-to vigorous-intensity aerobic exercise ("exercise,'' n = 117), c) a combination ("diet + exercise,'' n = 117), or d) control (n = 87). The reduced calorie diet had a 10% weight loss goal. The exercise intervention consisted of 45 min of moderate to vigorous aerobic activity 5 d.wk(-1) for 12 months. DNA repair capacity was measured in a subset of 226 women at baseline and 12 months from cryopreserved peripheral mononuclear cells using the comet assay. Anthropometric and body composition measures were performed at baseline and 12 months. Results: DNA repair capacity did not change significantly with any of the 12-month interventions compared with control; there were also no significant changes when stratified by changes in body composition or aerobic fitness ((V) over dotO(2max)). At baseline, DNA repair capacity was positively associated with weight, body mass index, and fat mass (r = 0.20, P = 0.003; r = 0.19, P = 0.004; r = 0.13, P = 0.04, respectively) and inversely with lean body mass (r = -0.14, P = 0.04). Conclusion: In conclusion, DNA repair capacity in cryopreserved PBMCs (Comet Assay) did not change with dietary weight loss or exercise interventions in postmenopausal women within a period of 12 months. Other assays that capture different facets of DNA repair function may be needed. C1 [Habermann, Nina; Abbenhardt, Clare; Ulrich, Cornelia M.] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany. [Habermann, Nina; Abbenhardt, Clare; Ulrich, Cornelia M.] Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany. [Makar, Karen W.; Xiao, Liren; Wang, Ching-Yun; Utsugi, Heidi K.; Duggan, Catherine; Mason, Caitlin E.; Imayama, Ikuyo; Mctiernan, Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Alfano, Catherine M.] NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA. [Campbell, Kristin L.] Univ British Columbia, Fac Med, Vancouver, BC, Canada. [Foster-Schubert, Karen E.; Mctiernan, Anne] Univ Washington, Sch Med, Seattle, WA USA. [Blackburn, George L.] Harvard Univ, Sch Med, Div Nutr, Boston, MA USA. [Potter, John D.; Ulrich, Cornelia M.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Potter, John D.; Mctiernan, Anne] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. RP Ulrich, CM (reprint author), Natl Ctr Tumor Dis, Div Prevent Oncol, Neuenheimer Feld 460, D-69120 Heidelberg, Germany. EM neli.ulrich@nct-heidelberg.de RI Duggan, Catherine/F-9414-2015; Biguzzi, Felipe/E-4724-2015; OI Duggan, Catherine/0000-0001-7369-4021; Potter, John/0000-0001-5439-1500 FU National Cancer Institute at the National Institutes of Health [U54-CA116847, R01 CA102504, 5KL2RR025015-03, R25 CA94880]; Canadian Institutes of Health Research FX This work was supported by the National Cancer Institute at the National Institutes of Health (grants U54-CA116847, R01 CA102504; 5KL2RR025015-03 to K.F.S; R25 CA94880 to A.K.) and Canadian Institutes of Health Research (fellowships to K.L.C and C.M.). None of the funding agencies were involved in the trial design or conduct. During the trial, Dr. Alfano was a faculty member at The Ohio State University and relocated to NCI after completion of her efforts on the NEW trial. NR 48 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2015 VL 47 IS 5 BP 896 EP 904 DI 10.1249/MSS.0000000000000480 PG 9 WC Sport Sciences SC Sport Sciences GA CG3CS UT WOS:000353155400002 PM 25160845 ER PT J AU Steeves, JA Bowles, HR Mcclain, JJ Dodd, KW Brychta, RJ Wang, J Chen, KY AF Steeves, Jeremy A. Bowles, Heather R. Mcclain, James J. Dodd, Kevin W. Brychta, Robert J. Wang, Juan Chen, Kong Y. TI Ability of Thigh-Worn ActiGraph and activPAL Monitors to Classify Posture and Motion SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE SITTING; STANDING; STEPPING; TRANSITIONS; ACTIVITIES; INCLINATION ID PHYSICAL-ACTIVITY; TIME SPENT; US ADULTS; OBESITY; VALIDATION; MORTALITY; CHILDREN; VALIDITY; DISEASE AB Purpose: This study compared sitting, standing, and stepping classifications from thigh-worn ActiGraph and activPAL monitors under laboratory and free-living conditions. Methods: Adults wore both monitors on the right thigh while performing activities (six sitting, two standing, nine stepping, and one cycling) and writing on a whiteboard with intermittent stepping under laboratory conditions (n = 21) and under free-living conditions for 3 d (n = 18). Percent time correctly classified was calculated under laboratory conditions. Between-monitor agreement and weighted kappa were calculated under free-living conditions. Results: In the laboratory, both monitors correctly classified 100% of standing time and >95% of the time spent in four of six sitting postures. Both monitors demonstrated misclassification of laboratory stool sitting time (ActiGraph 14% vs activPAL 95%). ActivPAL misclassified 14% of the time spent sitting with legs outstretched; ActiGraph was 100% accurate. Monitors were >95% accurate for stepping, although ActiGraph was less so for descending stairs (86%), ascending stairs (92%), and running at 2.91 m.s(-1) (93%). Monitors classified whiteboard writing differently (ActiGraph 83% standing/15% stepping vs activPAL 98% standing/2% stepping). ActivPAL classified 93% of cycling time as stepping, whereas ActiGraph classified <1% of cycling time as stepping. During free-living wear, monitors had substantial agreement (86% observed; weighted kappa = 0.77). Monitors classified similar amounts of time as sitting (ActiGraph 64% vs activPAL 62%). There were differences in time recorded as standing (ActiGraph 21% vs activPAL 27%) and stepping (ActiGraph 15% vs activPAL 11%). Conclusions: Differences in data processing algorithms may have resulted in the observed disagreement in posture and activity classification between thigh-worn ActiGraph and activPAL. Despite between-monitor agreement in classifying sitting time under free-living conditions, ActiGraph appears to be more sensitive to free-living upright walking motions than activPAL. C1 [Steeves, Jeremy A.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Rockville, MD 20892 USA. [Bowles, Heather R.; Mcclain, James J.] NCI, Risk Factor Monitoring & Methods Branch, Div Canc Control & Populat Sci, Rockville, MD 20892 USA. [Dodd, Kevin W.] NCI, Biometry Res Grp, Canc Prevent Div, Rockville, MD 20892 USA. [Brychta, Robert J.; Wang, Juan; Chen, Kong Y.] NIDDKD, Diabet Endocrinol & Obes Branch, Bethesda, MD USA. RP Steeves, JA (reprint author), NCI, Canc Prevent Fellowship Program, Canc Prevent Div, 9609 Med Ctr Dr,MSC 9762, Rockville, MD 20892 USA. EM steevesja@mail.nih.gov OI Chen, Kong/0000-0002-0306-1904 FU National Institutes of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health [Z01 DK07013, Z01 DK07014] FX This project was supported by the Intramural Research Program of the National Institutes of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health (grants Z01 DK07013 and Z01 DK07014). NR 32 TC 14 Z9 14 U1 2 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2015 VL 47 IS 5 BP 952 EP 959 DI 10.1249/MSS.0000000000000497 PG 8 WC Sport Sciences SC Sport Sciences GA CG3CS UT WOS:000353155400009 PM 25202847 ER PT J AU Rosales, T Sackett, DL Xu, JH Shi, ZD Xu, BY Li, HT Kaur, G Frohart, E Shenoy, N Cheal, SM Wu, HT Dulcey, AE Hu, YL Li, CH Lane, K Griffiths, GL Knutson, JR AF Rosales, Tilman Sackett, Dan L. Xu, Jianhua Shi, Zhen-Dan Xu, Biying Li, Haitao Kaur, Gurpreet Frohart, Erin Shenoy, Nalini Cheal, Sarah M. Wu, Haitao Dulcey, Andres E. Hu, Yulin Li, Changhui Lane, Kelly Griffiths, Gary L. Knutson, Jay R. TI STAQ: A Route Toward Low Power, Multicolor Nanoscopy SO MICROSCOPY RESEARCH AND TECHNIQUE LA English DT Article DE super resolution; STED; microscopy; imaging ID RESONANCE ENERGY-TRANSFER; STED MICROSCOPY; IN-VIVO; FLUORESCENCE MICROSCOPY; TUBULIN POLYMERIZATION; STIMULATED-EMISSION; RESOLUTION LIMIT; GFP; BEAM AB Nanoscopy has now become a real procedure in fluorescence microscopy of living cells. The STED/RESOLFT family of nanoscopy approaches has the best prospects for delivering high speed imaging, but the history of STED includes a continuing struggle to reduce the deactivation power applied, along with difficulties in achieving simultaneous multicolor images. In this manuscript, we present a concept for a similar real-time nanoscopy, using a new class of bipartite probes that separate the luminescent and quenching functions into two coupled molecules. In particular, the STAQ (Superresolution via Transiently Activated Quencher) example we show herein employs the excited state absorbance (not ground state) of the partner to accept energy from and quench the luminescent dye. The result is that much less deactivation power is needed for superresolved (approximate to 50 nm) imaging. Moreover, the TAQ partner excited by the donut beam is shown to quench several different visible dyes via the same mechanism, opening the door to easier multicolor imaging. We demonstrate three dyes sharing the same deactivation and show examples of superresolved multicolor images. We suggest STAQ will facilitate the growth of real-time nanoscopy by reducing confounding photodamage within living cells while expanding the nanoscopist's palette. Microsc. Res. Tech. 78:343-355, 2015. Published 2015. This article is a U.S. Government work and is in the public domain in the USA C1 [Rosales, Tilman; Xu, Jianhua; Knutson, Jay R.] NHLBI, Opt Spect Sect, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. [Sackett, Dan L.] NICHHD, Lab Integrat & Med Biophys, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Shi, Zhen-Dan; Xu, Biying; Li, Haitao; Kaur, Gurpreet; Frohart, Erin; Shenoy, Nalini; Cheal, Sarah M.; Wu, Haitao; Dulcey, Andres E.; Hu, Yulin; Li, Changhui; Lane, Kelly; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA. RP Knutson, JR (reprint author), 10 Ctr Dr,Bldg 10,Rm 5D14, Bethesda, MD 20892 USA. EM knutsonj@nhlbi.nih.gov FU NIH; NHLBI; NICHD FX Contract grant sponsors: Intramural Research Programs of the NIH, NHLBI, NICHD. NR 43 TC 0 Z9 0 U1 4 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-910X EI 1097-0029 J9 MICROSC RES TECHNIQ JI Microsc. Res. Tech. PD MAY PY 2015 VL 78 IS 5 BP 343 EP 355 DI 10.1002/jemt.22478 PG 13 WC Anatomy & Morphology; Biology; Microscopy SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics; Microscopy GA CG5PF UT WOS:000353344300003 PM 25762506 ER PT J AU Pobezinsky, LA Etzensperger, R Jeurling, S Alag, A Kadakia, T McCaughtry, TM Kimura, MY Sharrow, SO Guinter, TI Feigenbaum, L Singer, A AF Pobezinsky, Leonid A. Etzensperger, Ruth Jeurling, Susanna Alag, Amala Kadakia, Tejas McCaughtry, Tom M. Kimura, Motoko Y. Sharrow, Susan O. Guinter, Terry I. Feigenbaum, Lionel Singer, Alfred TI Let-7 microRNAs target the lineage-specific transcription factor PLZF to regulate terminal NKT cell differentiation and effector function SO NATURE IMMUNOLOGY LA English DT Article ID VITAMIN-D-RECEPTOR; T-CELLS; CAENORHABDITIS-ELEGANS; MESSENGER-RNAS; ENZYME DICER; LIN28; RECOGNITION; PATHWAY; PROTEIN; FAMILY AB Lethal-7 (let-7) microRNAs (miRNAs) are the most abundant miRNAs in the genome, but their role in developing thymocytes is unclear. We found that let-7 miRNAs targeted Zbtb16 mRNA, which encodes the lineage-specific transcription factor PLZF, to post-transcriptionally regulate PLZF expression and thereby the effector functions of natural killer T cells (NKT cells). Dynamic upregulation of let-7 miRNAs during the development of NKT thymocytes downregulated PLZF expression and directed their terminal differentiation into interferon-gamma (IFN-gamma)-producing NKT1 cells. Without upregulation of let-7 miRNAs, NKT thymocytes maintained high PLZF expression and terminally differentiated into interleukin 4 (IL-4)-producing NKT2 cells or IL-17-producing NKT17 cells. Upregulation of let-7 miRNAs in developing NKT thymocytes was signaled by IL-15, vitamin D and retinoic acid. Such targeting of a lineage-specific transcription factor by miRNA represents a previously unknown level of developmental regulation in the thymus. C1 [Pobezinsky, Leonid A.; Etzensperger, Ruth; Jeurling, Susanna; Alag, Amala; Kadakia, Tejas; McCaughtry, Tom M.; Kimura, Motoko Y.; Sharrow, Susan O.; Guinter, Terry I.; Singer, Alfred] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Feigenbaum, Lionel] NCI Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD USA. RP Singer, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM singera@nih.gov FU Intramural Research Program of the US National Institutes of Health; National Cancer Institute, Center for Cancer Research FX We thank N. Taylor and J.-H. Park for critical reading of the manuscript; G.Q. Daley (Harvard Medical School) for iLet7Delta LIN28 and M2rtTA double-transgenic mice; A. Bendelac (University of Chicago) for Zbtb16+/LU mice; the Tetramer Core Facility of the US National Institutes of Health for tetramer reagents; A. Adams and L. Granger for flow cytometry; and J.A. Williams (National Cancer Institute) for cDNA reagents. Supported by the Intramural Research Program of the US National Institutes of Health, the National Cancer Institute, Center for Cancer Research. NR 46 TC 20 Z9 20 U1 3 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2015 VL 16 IS 5 BP 517 EP U234 DI 10.1038/ni.3146 PG 9 WC Immunology SC Immunology GA CG5BN UT WOS:000353305200014 PM 25848867 ER PT J AU Wynn, TA AF Wynn, Thomas A. TI Type 2 cytokines: mechanisms and therapeutic strategies SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID ALTERNATIVELY ACTIVATED MACROPHAGES; ALLERGIC AIRWAY INFLAMMATION; REGULATORY T-CELLS; TUMOR-ASSOCIATED MACROPHAGES; IL-13 RECEPTOR ALPHA-2; MONOCYTE CHEMOATTRACTANT PROTEIN-1; HELMINTH INFECTION PROTECTS; BRONCHIAL EPITHELIAL-CELLS; INNATE LYMPHOID-CELLS; HOUSE-DUST MITE AB Type 2 immune responses are defined by the cytokines interleukin-4 (IL-4), IL-5, IL-9 and IL-13, which can either be host protective or have pathogenic activity. Type 2 immunity promotes antihelminth immunity, suppresses type 1-driven autoimmune disease, neutralizes toxins, maintains metabolic homeostasis, and regulates wound repair and tissue regeneration pathways following infection or injury. Nevertheless, when type 2 responses are dysregulated, they can become important drivers of disease. Type 2 immunity induces a complex inflammatory response characterized by eosinophils, mast cells, basophils, type 2 innate lymphoid cells, IL-4-and/or IL-13-conditioned macrophages and T helper 2 (TH2) cells, which are crucial to the pathogenesis of many allergic and fibrotic disorders. As chronic type 2 immune responses promote disease, the mechanisms that regulate their maintenance are thought to function as crucial disease modifiers. This Review discusses the many endogenous negative regulatory mechanisms that antagonize type 2 immunity and highlights how therapies that target some of these pathways are being developed to treat type 2-mediated disease. C1 NIAID, Immunopathogenesis Sect, Program Barrier Immun & Repair, Parasit Dis Lab,NIH, Bethesda, MD 20892 USA. RP Wynn, TA (reprint author), NIAID, Immunopathogenesis Sect, Program Barrier Immun & Repair, Parasit Dis Lab,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA FX The author is supported by the intramural research programme of the National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA. NR 186 TC 66 Z9 68 U1 11 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 EI 1474-1741 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD MAY PY 2015 VL 15 IS 5 BP 271 EP 282 DI 10.1038/nri3831 PG 12 WC Immunology SC Immunology GA CG6YV UT WOS:000353449800008 PM 25882242 ER PT J AU Soltesz, I Alger, BE Kano, M Lee, SH Lovinger, DM Ohno-Shosaku, T Watanabe, M AF Soltesz, Ivan Alger, Bradley E. Kano, Masanobu Lee, Sang-Hun Lovinger, David M. Ohno-Shosaku, Takako Watanabe, Masahiko TI Weeding out bad waves: towards selective cannabinoid circuit control in epilepsy SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID LONG-TERM DEPRESSION; TEMPORAL-LOBE EPILEPSY; FRAGILE-X-SYNDROME; DIACYLGLYCEROL LIPASE-ALPHA; HIPPOCAMPAL PYRAMIDAL CELLS; PHOSPHOLIPASE-C-BETA; SPIKING BASKET CELLS; IN-VIVO EXPOSURE; ENDOCANNABINOID SYSTEM; ENDOGENOUS CANNABINOIDS AB Endocannabinoids are lipid-derived messengers, and both their synthesis and breakdown are under tight spatiotemporal regulation. As retrograde signalling molecules, endocannabinoids are synthesized postsynaptically but activate presynaptic cannabinoid receptor 1 (CB1) receptors to inhibit neurotransmitter release. In turn, CB1-expressing inhibitory and excitatory synapses act as strategically placed control points for activity-dependent regulation of dynamically changing normal and pathological oscillatory network activity. Here, we highlight emerging principles of cannabinoid circuit control and plasticity, and discuss their relevance for epilepsy and related comorbidities. New insights into cannabinoid signalling may facilitate the translation of the recent interest in cannabis-related substances as antiseizure medications to evidence-based treatment strategies. C1 [Soltesz, Ivan; Lee, Sang-Hun] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92697 USA. [Alger, Bradley E.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. [Kano, Masanobu] Univ Tokyo, Grad Sch Med, Dept Neurophysiol, Tokyo 1130033, Japan. [Lovinger, David M.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Ohno-Shosaku, Takako] Kanazawa Univ, Grad Sch Med Sci, Dept Impairment Study, Kanazawa, Ishikawa 9200942, Japan. [Watanabe, Masahiko] Hokkaido Univ, Grad Sch Med, Dept Anat, Sapporo, Hokkaido 0608638, Japan. RP Soltesz, I (reprint author), Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92697 USA. EM isoltesz@uci.edu RI WATANABE, Masahiko/A-4055-2012; Ohno-Shosaku, Takako/C-3250-2015; OI Soltesz, Ivan/0000-0003-1493-3744 FU US National Institutes of Health grant [NS74432]; Ministry of Education, Culture, Sports, Science and Technology of Japan [23500466, 25000015] FX The authors thank J. G. Malpeli for comments on the manuscript and M. Uchigashima for Figure 1c. This work was supported by a US National Institutes of Health grant (NS74432 to I.S.) and Grants-in-Aid for Scientific Research (23500466 to T.O.-S. and 25000015 to M.K.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. NR 153 TC 24 Z9 24 U1 5 U2 37 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X EI 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD MAY PY 2015 VL 16 IS 5 BP 264 EP 277 DI 10.1038/nrn3937 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CG4CO UT WOS:000353229800006 PM 25891509 ER PT J AU Xie, LK Qi, Y Subashi, E Liao, G Miller-DeGraff, L Jetten, AM Johnson, GA AF Xie, Luke Qi, Yi Subashi, Ergys Liao, Grace Miller-DeGraff, Laura Jetten, Anton M. Johnson, G. Allan TI 4D MRI of polycystic kidneys from rapamycin-treated Glis3-deficient mice SO NMR IN BIOMEDICINE LA English DT Article DE small animal preclinical imaging; MRI; MR microscopy; three-dimensional dynamic contrast-enhanced; polycystic kidney disease; Glis3 protein ID GLOMERULAR-FILTRATION-RATE; NEONATAL DIABETES-MELLITUS; VOLUME PROGRESSION; MOUSE MODEL; DISEASE; BIOMARKERS; PERFUSION; INSIGHTS; INJURY; GLIS3 AB Polycystic kidney disease (PKD) is a life-threatening disease that leads to a grotesque enlargement of the kidney and significant loss of function. Several imaging studies with MRI have demonstrated that cyst size in polycystic kidneys can determine disease severity and progression. In the present study, we found that, although kidney volume and cyst volume decreased with drug treatment, renal function did not improve with treatment. Here, we applied dynamic contrast-enhanced MRI to study PKD in a Glis3 (GLI-similar 3)-deficient mouse model. Cysts from this model have a wide range of sizes and develop at an early age. To capture this crucial stage and assess cysts in detail, we imaged during early development (3-17 weeks) and applied high spatiotemporal resolution MRI (125x125x125cubic microns every 7.7s). A drug treatment with rapamycin (also known as sirolimus) was applied to determine whether disease progression could be halted. The effect and synergy (interaction) of aging and treatment were evaluated using an analysis of variance (ANOVA). Structural measurements, including kidney volume, cyst volume and cyst-to-kidney volume ratio, changed significantly with age. Drug treatment significantly decreased these metrics. Functional measurements of time-to-peak (TTP) mean and TTP variance were determined. TTP mean did not change with age, whereas TTP variance increased with age. Treatment with rapamycin generally did not affect these functional metrics. Synergistic effects of treatment and age were not found for any measurements. Together, the size and volume ratio of cysts decreased with drug treatment, whereas renal function remained the same. The quantification of renal structure and function with MRI can comprehensively assess the pathophysiology of PKD and response to treatment. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Xie, Luke; Qi, Yi; Subashi, Ergys; Johnson, G. Allan] Duke Univ, Med Ctr, Dept Radiol, Ctr Vivo Microscopy, Durham, NC 27710 USA. [Xie, Luke; Johnson, G. Allan] Duke Univ, Dept Biomed Engn, Durham, NC 27710 USA. [Subashi, Ergys] Duke Univ, Med Ctr, Med Phys Grad Program, Durham, NC 27710 USA. [Liao, Grace; Miller-DeGraff, Laura; Jetten, Anton M.] NIEHS, Cell Biol Sect, Immun Inflammat & Dis Lab, Div Intramural Res,NIH, Res Triangle Pk, NC 27709 USA. RP Johnson, GA (reprint author), Duke Univ, Med Ctr, Dept Radiol, Ctr Vivo Microscopy, Box 3302, Durham, NC 27710 USA. EM gjohnson@duke.edu OI Jetten, Anton/0000-0003-0954-4445 FU National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering Biomedical Technology Resource Center [P41 EB015897]; National Institutes of Health/National Institute of Environmental Health Sciences Intramural Research Program [Z01 ES100485] FX This work was supported by the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering Biomedical Technology Resource Center (P41 EB015897 to G.A.J.), and by the National Institutes of Health/National Institute of Environmental Health Sciences Intramural Research Program (Z01 ES100485 to A.M.J.). NR 43 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3480 EI 1099-1492 J9 NMR BIOMED JI NMR Biomed. PD MAY PY 2015 VL 28 IS 5 BP 546 EP 554 DI 10.1002/nbm.3281 PG 9 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA CG9PX UT WOS:000353650100004 PM 25810360 ER PT J AU Indaram, M Agron, E Clemons, TE Sperduto, RD Wong, WT Ferris, FL Chew, EY AF Indaram, Maanasa Agron, Elvira Clemons, Traci E. Sperduto, Robert D. Wong, Wai T. Ferris, Frederick L., III Chew, Emily Y. CA Age Related Eye Dis Study Res Grp TI Changes in Lens Opacities on the Age-Related Eye Disease Study Grading Scale Predict Progression to Cataract Surgery and Vision Loss SO OPHTHALMOLOGY LA English DT Article ID BLUE MOUNTAINS EYE; II LOCS-II; REGRESSION; AREDS AB Purpose: To investigate whether the 2-year change in lens opacity severity on the Age-Related Eye Disease Study (AREDS) lens grading scale predicts progression to cataract surgery or loss of visual acuity by 5 years. Design: Prospective cohort study within a randomized clinical trial of oral supplements. Participants: The AREDS participants whose eyes were phakic at baseline and free of late age-related macular degeneration throughout the study. Methods: Baseline and annual lens photographs of AREDS participants (n = 3466/4757; 73%) were graded for severity of cataracts using the AREDS system for classifying cataracts from photographs. Clinical examinations conducted semiannually collected data on cataract surgery and visual acuity. Association of the change in lens opacities at 2 years with these outcomes at 5 years was analyzed with adjusted Cox proportional hazard models. Main Outcome Measurements: Progression of lens opacities on stereoscopic lens photographs at 2 years, cataract surgery, and visual acuity loss of 2 lines or more at 5 years. Results: The adjusted hazard ratios (HRs) for association of progression to cataract surgery at 5 years were: nuclear cataract increase of 1.0 unit or more compared with less than 1.0-unit change at 2 years, 2.77 (95% confidence interval [CI], 2.07-3.70; P < 0.001); cortical cataract increase of 5% or more in lens opacity in the central 5 mm of the lens compared with less than 5% increase at 2 years, 1.91 (95% CI, 1.27-2.87; P = 0.002); and posterior subcapsular cataract increase of 5% or more versus less than 5% in the central 5 mm of the lens, 8.25 (95% CI, 5.55-12.29; P < 0.001). Similarly, HRs of vision loss of 2 lines or more at 5 years for this degree of lens changes at 2 years were the following: nuclear, 1.83 (95% CI, 1.49-2.25; P < 0.001); cortical, 1.13 (95% CI, 0.78-1.65; P = 0.519); and posterior subcapsular cataract, 3.05 (95% CI, 1.79-5.19; P < 0.001). Conclusions: Two-year changes in severity of lens opacities on the AREDS lens grading scale are predictive of long-term clinically relevant outcomes, making them potential surrogate end points in follow-up studies. (C) 2015 by the American Academy of Ophthalmology. C1 [Indaram, Maanasa; Agron, Elvira; Ferris, Frederick L., III; Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Clemons, Traci E.; Sperduto, Robert D.] EMMES Corp, Rockville, MD USA. [Wong, Wai T.] NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bethesda, MD 20892 USA. RP Chew, EY (reprint author), NEI, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov RI Wong, Wai/B-6118-2017; OI Wong, Wai/0000-0003-0681-4016; Indaram, Maanasa/0000-0001-6228-3307 FU National Eye Institute, National Institutes of Health, Bethesda, Maryland [NOI-EY-0-2127] FX Supported by the National Eye Institute, National Institutes of Health, Bethesda, Maryland (grant no.: NOI-EY-0-2127). Maanasa Indaram performed this work as part of the Howard Hughes Scholars Program at the National Institutes of Health. NR 18 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2015 VL 122 IS 5 BP 888 EP 896 DI 10.1016/j.ophtha.2014.12.037 PG 9 WC Ophthalmology SC Ophthalmology GA CG5NB UT WOS:000353337600013 PM 25682177 ER PT J AU Muterko, A Kalendar, R Cockram, J Balashova, I AF Muterko, Alexandr Kalendar, Ruslan Cockram, James Balashova, Irina TI Discovery, evaluation and distribution of haplotypes and new alleles of the Photoperiod-A1 gene in wheat SO PLANT MOLECULAR BIOLOGY LA English DT Article DE Cereal; Flowering time; Genetic variation; Heteroduplex mobility assay; Molecular evolution; Photoperiod response; Ppd-A1 haplotype; Wheat ID HETERODUPLEX MOBILITY ASSAY; PSEUDO-RESPONSE-REGULATOR; TRITICUM-AESTIVUM L.; FLOWERING TIME; DNA HETERODUPLEXES; GENOME EVOLUTION; FERTILE CRESCENT; CONSTANS; DOMESTICATION; BARLEY AB Photoperiod response in wheat is determined to a large extent by the homoeologous series of Photoperiod 1 (Ppd1) genes. In this study, Ppd-A1 genomic sequences from the 5' UTR and promoter region were analysed in 104 accessions of six tetraploid wheat species (Triticum dicoccoides, T. dicoccum, T. turgidum, T. polonicum, T. carthlicum, T. durum) and 102 accessions of six hexaploid wheat species (T. aestivum, T. compactum, T. sphaerococcum, T. spelta, T. macha, T. vavilovii). This data was supplemented with in silico analysis of publicly available sequences from 46 to 193 accessions of diploid and tetraploid wheat, respectively. Analysis of a region of the Ppd-A1 promoter identified thirteen haplotypes, which were divided in two haplogroups. Distribution of the Ppd-A1 haplogroups and haplotypes in wheat species, and their geographical distributions were analysed. Polymerase chain reaction combined with a heteroduplex mobility assay was subsequently used to efficiently discriminate between Ppd-A1 alleles, allowing identification of the Ppd-A1b haplotypes and haplogroups. The causes of anomalous migration of Ppd-A1 heteroduplexes in gels were found to be the localization of mismatches relative to the center of fragment, the cumulative effect of neighbouring polymorphic sites, and the location of mismatches within A/T-tracts. Analysis of the Ppd-A1 5' UTR in hexaploid wheat revealed a novel mutation within the "photoperiod critical" region in a subset of T. compactum accessions. This putative photoperiod insensitive allele (designated Ppd-A1a.4) includes a 684 bp deletion which spans region in common with deletions previously identified in other photoperiod insensitive Ppd1 alleles. C1 [Muterko, Alexandr; Balashova, Irina] Breeding & Genet Inst Natl Ctr Seed & Cultivar In, Dept Genom & Biotechnol, UA-65036 Odessa, Ukraine. [Kalendar, Ruslan] RSE Natl Ctr Biotechnol, Lab Plant Genom & Bioinformat, Astana 010000, Kazakhstan. [Cockram, James] NIAB, Cambridge CB3 0LE, England. RP Muterko, A (reprint author), Breeding & Genet Inst Natl Ctr Seed & Cultivar In, Dept Genom & Biotechnol, Ovidiopolskaya Rd 3, UA-65036 Odessa, Ukraine. EM muterko@gmail.com RI Kalendar, Ruslan/D-9751-2012; OI Kalendar, Ruslan/0000-0003-3986-2460; Muterko, Alexandr/0000-0002-9083-9162 NR 55 TC 3 Z9 3 U1 4 U2 25 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-4412 EI 1573-5028 J9 PLANT MOL BIOL JI Plant Mol.Biol. PD MAY PY 2015 VL 88 IS 1-2 BP 149 EP 164 DI 10.1007/s11103-015-0313-2 PG 16 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA CG6IQ UT WOS:000353403600011 PM 25851614 ER PT J AU Mashalidis, EH Gittis, AG Tomczak, A Abell, C Barry, CE Garboczi, DN AF Mashalidis, Ellene H. Gittis, Apostolos G. Tomczak, Aurelie Abell, Chris Barry, Clifton E., III Garboczi, David N. TI Molecular insights into the binding of coenzyme F-420 to the conserved protein Rv1155 from Mycobacterium tuberculosis SO PROTEIN SCIENCE LA English DT Article DE Mycobacterium tuberculosis; Rv1155; coenzyme F-420; conserved hypothetical protein ID PYRIDOXINE 5'-PHOSPHATE OXIDASE; BACTERIAL LUCIFERASE FAMILY; F-420-DEPENDENT GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; CRYSTAL-STRUCTURE; DRUG DISCOVERY; SYSTEM; PA-824; SMEGMATIS; FLAVIN; IDENTIFICATION AB Coenzyme F-420 is a deazaflavin hydride carrier with a lower reduction potential than most flavins. In Mycobacterium tuberculosis (Mtb), F-420 plays an important role in activating PA-824, an antituberculosis drug currently used in clinical trials. Although F-420 is important to Mtb redox metabolism, little is known about the enzymes that bind F-420 and the reactions that they catalyze. We have identified a novel F-420-binding protein, Rv1155, which is annotated in the Mtb genome sequence as a putative flavin mononucleotide (FMN)-binding protein. Using biophysical techniques, we have demonstrated that instead of binding FMN or other flavins, Rv1155 binds coenzyme F-420. The crystal structure of the complex of Rv1155 and F-420 reveals one F-420 molecule bound to each monomer of the Rv1155 dimer. Structural, biophysical, and bioinformatic analyses of the Rv1155-F-420 complex provide clues about its role in the bacterium. C1 [Mashalidis, Ellene H.] NIAID, TB Res Sect, Bethesda, MD 20892 USA. [Mashalidis, Ellene H.; Abell, Chris] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England. [Gittis, Apostolos G.; Garboczi, David N.] NIAID, Struct Biol Sect, Res Technol Branch, Rockville, MD 20852 USA. [Tomczak, Aurelie] NIAID, Mol Signaling Sect, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Garboczi, DN (reprint author), Twinbrook 2 Rm 110,12441 Parklawn Dr, Rockville, MD 20852 USA. EM dgarboczi@niaid.nih.gov RI Barry, III, Clifton/H-3839-2012 FU NIH, NIAID FX Grant sponsor: Intramural Research Program of the NIH, NIAID. NR 52 TC 5 Z9 5 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0961-8368 EI 1469-896X J9 PROTEIN SCI JI Protein Sci. PD MAY PY 2015 VL 24 IS 5 BP 729 EP 740 DI 10.1002/pro.2645 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CG7YV UT WOS:000353524700015 PM 25644473 ER PT J AU Leggio, L Zywiak, WH Edwards, SM Tidey, JW Swift, RM Kenna, GA AF Leggio, Lorenzo Zywiak, William H. Edwards, Steven M. Tidey, Jennifer W. Swift, Robert M. Kenna, George A. TI A preliminary double-blind, placebo-controlled randomized study of baclofen effects in alcoholic smokers (vol 232, pg 233, 2015) SO PSYCHOPHARMACOLOGY LA English DT Correction C1 [Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. [Leggio, Lorenzo] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [Leggio, Lorenzo] Brown Univ, Dept Behav & Social Sci, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Zywiak, William H.] PIRE, Decis Sci Inst, Pawtucket, RI USA. [Zywiak, William H.] Butler Hosp, Providence, RI 02906 USA. [Zywiak, William H.; Tidey, Jennifer W.; Swift, Robert M.; Kenna, George A.] Brown Univ, Dept Psychiat & Human Behav, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Edwards, Steven M.] Univ Nebraska, Dept Psychol, Lincoln, NE 68588 USA. [Swift, Robert M.] Vet Affairs Med Ctr, Providence, RI USA. [Swift, Robert M.] Roger Williams Med Ctr, Providence, RI USA. RP Leggio, L (reprint author), NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,10CRC 15330,MSC 1108,Room 1-5429, Bethesda, MD 20892 USA. EM lorenzo.leggio@nih.gov RI Leggio, Lorenzo/M-2972-2016 NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2015 VL 232 IS 9 BP 1667 EP 1667 DI 10.1007/s00213-015-3916-z PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CF8DW UT WOS:000352786900015 PM 25804430 ER PT J AU Soto, PL Grandy, DK Hursh, SR Katz, JL AF Soto, Paul L. Grandy, David K. Hursh, Steven R. Katz, Jonathan L. TI Behavioral economics of food reinforcement and the effects of prefeeding, extinction, and eticlopride in dopamine D-2 receptor mutant mice (vol 215, pg 775, 2015) SO PSYCHOPHARMACOLOGY LA English DT Correction C1 [Soto, Paul L.; Hursh, Steven R.] Johns Hopkins Univ, Div Behav Biol, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Grandy, David K.] Oregon Hlth & Sci Univ, Portland, OR USA. [Katz, Jonathan L.] NIDA, Baltimore, MD USA. RP Soto, PL (reprint author), Johns Hopkins Univ, Div Behav Biol, Dept Psychiat & Behav Sci, Ross 469,720 Rutland Ave, Baltimore, MD 21205 USA. EM psoto@jhmi.edu NR 1 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2015 VL 232 IS 9 BP 1669 EP 1669 DI 10.1007/s00213-015-3918-x PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CF8DW UT WOS:000352786900016 PM 25814138 ER PT J AU Kahn, JA Rudy, BJ Xu, JH Secord, EA Kapogiannis, BG Thornton, S Gillison, ML AF Kahn, Jessica A. Rudy, Bret J. Xu, Jiahong Secord, Elizabeth A. Kapogiannis, Bill G. Thornton, Sarah Gillison, Maura L. TI Behavioral, Immunologic, and Virologic Correlates of Oral Human Papillomavirus Infection in HIV-Infected Youth SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID HPV INFECTION; UNITED-STATES; NECK CANCERS; PREVALENCE; POPULATION; WOMEN; RISK; ADOLESCENTS; HEAD; CHILDREN AB Background: Little is known about the epidemiology or risk factors for oral human papillomavirus (HPV) in HIV-infected youth. The objectives of this study were to determine the prevalence and correlates of oral HPV infection and to explore the association between HPV vaccination and oral infection in HIV-infected youth. Methods: Youth 12 to 24 years of age with behaviorally acquired HIV were recruited for this cross-sectional study. Procedures involved medical chart review, survey, and collection of an oral rinse sample. Univariable and multivariable logistic regression models were used to determine whether demographic, behavioral, immunologic, and virologic factors and history of vaccination were significantly associated with oral HPV infection. Results: Mean age of the 272 participants was 21.5 years; 64% were non-Hispanic black and 20.2% were Hispanic; and 10.8% of men compared with 20.3% of women were fully vaccinated. Human papillomavirus prevalence was 19.7% in men and 18.6% in women (P = 1.0). Only men were positive for vaccine-type HPV: 5.6% were positive for HPV-6, HPV-11, HPV-16, and/or HPV-18, and 4.2% were positive for HPV-16 and/or HPV-18. Among men who were fully vaccinated, none were positive for HPV-6, HPV-11, HPV-16, and/or HPV-18, compared with 12 (6.3%) of men who were not fully vaccinated (P = 0.37). Two variables were marginally associated with oral HPV (P < 0.10): marijuana use in the previous 3 months and lower CD4+ T-cell count. Conclusions: Prevalence rates of oral HPV were relatively high in this population of HIV-infected youth and were similar in male and female youth. No fully vaccinated men were infected with vaccine-type HPV. C1 [Kahn, Jessica A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Kahn, Jessica A.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Rudy, Bret J.] NYU, Sch Med, New York, NY USA. [Xu, Jiahong; Thornton, Sarah] WESTAT Corp, Rockville, MD 20850 USA. [Secord, Elizabeth A.] Wayne State Univ, Detroit, MI USA. [Kapogiannis, Bill G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Rockville, MD USA. [Gillison, Maura L.] Ohio State Univ, Columbus, OH 43210 USA. RP Kahn, JA (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Adolescent Med, MLC 4000,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM jessica.kahn@cchmc.org FU NCATS NIH HHS [UL1 TR001082]; NICHD NIH HHS [5 U01HD 40474, U01 HD040474, U01 HD040533, U01 HD068030, U01-HD040533] NR 36 TC 3 Z9 3 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-5717 EI 1537-4521 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD MAY PY 2015 VL 42 IS 5 BP 246 EP 252 DI 10.1097/OLQ.0000000000000264 PG 7 WC Infectious Diseases SC Infectious Diseases GA CG1QY UT WOS:000353049700004 PM 25868136 ER PT J AU Rosenberg, M Pettifor, A Lippman, SA Thirumurthy, H Emch, M Miller, WC Selin, A Gomez-Olive, FX Hughes, JP Laeyendecker, O Tollman, S Kahn, K AF Rosenberg, Molly Pettifor, Audrey Lippman, Sheri A. Thirumurthy, Harsha Emch, Michael Miller, William C. Selin, Amanda Gomez-Olive, Francesc Xavier Hughes, James P. Laeyendecker, Oliver Tollman, Stephen Kahn, Kathleen TI Relationship Between Community-Level Alcohol Outlet Accessibility and Individual-Level Herpes Simplex Virus Type 2 Infection Among Young Women in South Africa SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID INTIMATE PARTNER VIOLENCE; HIV PREVALENCE; PUBLIC-HEALTH; CONSUMPTION; DRINKING; DENSITY; AVAILABILITY; ASSOCIATION; METAANALYSIS; POPULATION AB Background: Exposure to alcohol outlets may influence sexual health outcomes at the individual and community levels. Visiting alcohol outlets facilitates alcohol consumption and exposes patrons to a risky environment and network of potential partners, whereas the presence of alcohol outlets in the community may shift social acceptance of riskier behavior. We hypothesize that living in communities with more alcohol outlets is associated with increased sexual risk. Methods: We performed a cross-sectional analysis in a sample of 2174 South African schoolgirls (ages 13-21 years) living across 24 villages in the rural Agincourt subdistrict, underpinned by long-term health and sociodemographic surveillance. To examine the association between number of alcohol outlets in village of residence and individual-level prevalent herpes simplex virus type 2 (HSV-2) infection, we used generalized estimating equations with logit links, adjusting for individual-and villagelevel covariates. Results: The median number of alcohol outlets per village was 3 (range, 0-7). Herpes simplex virus type 2 prevalence increased from villages with no outlets (1.4%[95% confidence interval, 0.2-12.1]), to villages with 1 to 4 outlets (4.5% [3.7-5.5]), and to villages with more than 4 outlets (6.3% [5.6, 7.1]). An increase of 1 alcohol outlet per village was associated with an 11% increase in the odds of HSV-2 infection (adjusted odds ratio [95% confidence interval], 1.11 [0.98-1.25]). Conclusions: Living in villages with more alcohol outlets was associated with increased prevalence of HSV-2 infection in young women. Structural interventions and sexual health screenings targeting villages with extensive alcohol outlet environments could help prevent the spread of sexually transmitted infections. C1 [Rosenberg, Molly] Harvard Univ, Ctr Populat & Dev Studies, Sch Publ Hlth, Cambridge, MA 02138 USA. [Rosenberg, Molly; Pettifor, Audrey; Emch, Michael; Miller, William C.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Rosenberg, Molly; Pettifor, Audrey; Thirumurthy, Harsha; Emch, Michael; Selin, Amanda] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA. [Pettifor, Audrey; Lippman, Sheri A.; Tollman, Stephen; Kahn, Kathleen] Univ Witwatersrand, Sch Publ Hlth, MRC Wits Rural Publ Hlth & Hlth Transit Res Unit, Fac Hlth Sci, Johannesburg, South Africa. [Lippman, Sheri A.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, Dept Med, San Francisco, CA USA. [Thirumurthy, Harsha] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Emch, Michael] Univ N Carolina, Sch Med, Dept Geog, Chapel Hill, NC USA. [Miller, William C.] Univ N Carolina, Sch Med, Div Infect Dis, Dept Med, Chapel Hill, NC USA. [Tollman, Stephen; Kahn, Kathleen] INDEPTH Network, Accra, Ghana. [Hughes, James P.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Laeyendecker, Oliver] NIAID, Immunoregulat Lab, NIH, Baltimore, MD USA. [Laeyendecker, Oliver] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Tollman, Stephen; Kahn, Kathleen] Umea Univ, Ctr Global Hlth Res, Umea, Sweden. RP Rosenberg, M (reprint author), Harvard Univ, Ctr Populat & Dev Studies, 9 Bow St, Cambridge, MA 02138 USA. EM mrosenb@hsph.harvard.edu OI Laeyendecker, Oliver/0000-0002-6429-4760 FU NIAID NIH HHS [U01 AI069423, 5U01AI069423-04, UM1 AI068617, UM1 AI068613, UM1 AI068619]; NICHD NIH HHS [P2C HD050924, T32 HD007168, R24 HD050924]; NIMH NIH HHS [R01 MH087118, R21 MH090887, 1R21MH090887-01, 5R01MH087118-02]; Wellcome Trust [058893/Z/99/A, 069683/Z/02/Z, 085477/Z/08/Z] NR 34 TC 0 Z9 0 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-5717 EI 1537-4521 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD MAY PY 2015 VL 42 IS 5 BP 259 EP 265 DI 10.1097/OLQ.0000000000000263 PG 7 WC Infectious Diseases SC Infectious Diseases GA CG1QY UT WOS:000353049700006 PM 25868138 ER PT J AU Huang, XS Wang, Y Yan, W Smith, C Ye, ZH Wang, J Gao, YX Mendelsohn, L Cheng, LZ AF Huang, Xiaosong Wang, Ying Yan, Wei Smith, Cory Ye, Zhaohui Wang, Jing Gao, Yongxing Mendelsohn, Laurel Cheng, Linzhao TI Production of Gene-Corrected Adult Beta Globin Protein in Human Erythrocytes Differentiated From Patient iPSCs After Genome Editing of the Sickle Point Mutation SO STEM CELLS LA English DT Article DE Human iPSCs; Genome editing; Erythroid cells; Globin switching ID PLURIPOTENT STEM-CELLS; ZINC-FINGER NUCLEASES; RED-BLOOD-CELLS; HOMOLOGOUS RECOMBINATION; HUMAN ERYTHROBLASTS; IN-VIVO; GENERATION; ERYTHROPOIESIS; CRISPR/CAS9; TALEN AB Human induced pluripotent stem cells (iPSCs) and genome editing provide a precise way to generate gene-corrected cells for disease modeling and cell therapies. Human iPSCs generated from sickle cell disease ( SCD) patients have a homozygous missense point mutation in the HBB gene encoding adult beta-globin proteins, and are used as a model system to improve strategies of human gene therapy. We demonstrate that the CRISPR/Cas9 system designer nuclease is much more efficient in stimulating gene targeting of the endogenous HBB locus near the SCD point mutation in human iPSCs than zinc finger nucleases and TALENs. Using a specific guide RNA and Cas9, we readily corrected one allele of the SCD HBB gene in human iPSCs by homologous recombination with a donor DNA template containing the wild-type HBB DNA and a selection cassette that was subsequently removed to avoid possible interference of HBB transcription and translation. We chose targeted iPSC clones that have one corrected and one disrupted SCD allele for erythroid differentiation assays, using an improved xeno-free and feeder-free culture condition we recently established. Erythrocytes from either the corrected or its parental ( uncorrected) iPSC line were generated with similar efficiencies. Currently similar to 6%-10% of these differentiated erythrocytes indeed lacked nuclei, characteristic of further matured erythrocytes called reticulocytes. We also detected the 16-kDa beta-globin protein expressed from the corrected HBB allele in the erythrocytes differentiated from genome-edited iPSCs. Our results represent a significant step toward the clinical applications of genome editing using patient-derived iPSCs to generate disease-free cells for cell and gene therapies. C1 [Huang, Xiaosong; Yan, Wei; Smith, Cory; Ye, Zhaohui; Wang, Jing; Gao, Yongxing; Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Dept Med, Div Hematol, Baltimore, MD 21205 USA. [Huang, Xiaosong; Wang, Ying; Yan, Wei; Smith, Cory; Ye, Zhaohui; Wang, Jing; Gao, Yongxing; Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD USA. [Smith, Cory; Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Predoctoral Training Program Human Genet, Baltimore, MD USA. [Wang, Ying] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD USA. [Mendelsohn, Laurel] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Cheng, LZ (reprint author), Miller Res Bldg 747,733 North Broadway, Baltimore, MD 21205 USA. EM lcheng2@jhmi.edu FU Maryland State Stem Cell Research Fund [2011-MSCRFII-0088, 2011-MSCRFE-0087]; NIH [2R01 HL-073781, U01 HL107446, T32HL007525-31]; Edythe Harris Lucas and Clara Lucas Lynn Chair in Hematology of Johns Hopkins University FX We thank Dr. Xiuli An at NYBC for providing Band 3 antibodies, Dr. J. Keith Joung in MGH for providing the MGH donor vector, and Drs. Evan Braunstein and Robert Brodsky for discussions and critical reading. This work was supported in part by grants from Maryland State Stem Cell Research Fund (2011-MSCRFII-0088 and 2011-MSCRFE-0087) and from NIH (2R01 HL-073781, U01 HL107446, and T32HL007525-31). L.C. is also supported by Edythe Harris Lucas and Clara Lucas Lynn Chair in Hematology of Johns Hopkins University. NR 47 TC 36 Z9 38 U1 6 U2 37 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD MAY PY 2015 VL 33 IS 5 BP 1470 EP 1479 DI 10.1002/stem.1969 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA CG4XM UT WOS:000353292600009 PM 25702619 ER PT J AU Chen, P Denniston, AK Hirani, S Hannes, S Nussenblatt, RB AF Chen, Ping Denniston, Alastair K. Hirani, Sima Hannes, Susan Nussenblatt, Robert B. TI Role of dendritic cell subsets in immunity and their contribution to noninfectious uveitis SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE conventional dendritic cells; myeloid dendritic cells; plasmacytoid dendritic cells; noninfectious uveitis; experimental autoimmune uveitis ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; COLONY-STIMULATING FACTOR; MOUSE BONE-MARROW; T-CELLS; PERIPHERAL-BLOOD; RETINAL ANTIGENS; INTERFERON-ALPHA; LYMPHOID ORGANS; AQUEOUS-HUMOR; FLT3 LIGAND AB Dendritic cells (DCs) are a heterogeneous population. Murine DCs consist of conventional DCs (cDCs) and plasmacytoid DCs (pDCs). In humans, the analogous populations are myeloid DCs (mDCs) and pDCs. Though distinct in phenotypes and functions, studies have shown that these DC subsets may interact or "crosstalk" during immune responses. For example, cDCs may facilitate pDC maturation, and pDCs may enhance antigen presentation of cDCs in certain pathogenic conditions or even take on a cDC phenotype themselves. The role of DCs in noninfectious uveitis has been studied primarily in the experimental autoimmune uveitis mouse model and to a more limited extent in patients. Recent evidence shows that the number, phenotype, and function of DC subsets are altered in this disease. We provide an overview of selected recent developments of pDCs and cDCs/mDCs, with special attention to their interaction and the dual roles of DC subsets in noninfectious uveitis. Published by Elsevier Inc. C1 [Chen, Ping; Hirani, Sima; Hannes, Susan; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Denniston, Alastair K.] Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp Birmingham, Dept Ophthalmol, Birmingham, W Midlands, England. RP Nussenblatt, RB (reprint author), NEI, NIH, 9000 Rockville Pike,Bldg 10-10N109, Rockville, MD 20892 USA. EM nussenblattr@nei.nih.gov OI Denniston, Alastair/0000-0001-7849-0087 FU Intramural Research Program of the National Institute of Eye, NIH FX The research was supported by the Intramural Research Program of the National Institute of Eye, NIH. We thank Drs. Igal Gery, William Tucker, and Carlos Blades for critical reading of the manuscript. NR 71 TC 3 Z9 3 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 EI 1879-3304 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD MAY-JUN PY 2015 VL 60 IS 3 BP 242 EP 249 DI 10.1016/j.survophthal.2015.01.003 PG 8 WC Ophthalmology SC Ophthalmology GA CG6SP UT WOS:000353433000006 PM 25749202 ER PT J AU Tana, MM Zhao, XC Bradshaw, A Moon, MS Page, S Turner, T Rivera, E Kleiner, DE Heller, T AF Tana, Michele M. Zhao, Xiongce Bradshaw, Alyson Moon, Mi Sun Page, Sandy Turner, Tiffany Rivera, Elenita Kleiner, David E. Heller, Theo TI Factors associated with the platelet count in patients with chronic hepatitis C SO THROMBOSIS RESEARCH LA English DT Article DE Platelet biology; Non-invasive markers; Conceptual model ID COUNT/SPLEEN DIAMETER RATIO; CHRONIC LIVER-DISEASE; VIRUS-INFECTION; COMPENSATED CIRRHOSIS; ESOPHAGEAL-VARICES; THROMBOCYTOPENIA; THROMBOPOIETIN; FIBROSIS; DIAGNOSIS; FRACTION AB Background: There are many potential causes of thrombocytopenia in patients with chronic hepatitis C (CHC). Aims: We sought to determine the association between thrombopoietin (TPO) level, immature platelet fraction (IPF), immunoglobulin G (IgG) level, spleen size, and the platelet count in CHC. Methods: We studied a consecutive sample of patients enrolled in an observational study at a referral-based research center, excluding subjects based on eligibility criteria. TPO, glycocalicin, and von Willebrand Factor (vWF) levels were determined using stored sera. Hepatic fibrosis was assessed via transient elastography (TE) when available, and clinical laboratory values and radiologic data were obtained from the medical record. We performed analyses of the relationships between independent variables and the platelet count. Results: On univariate analysis, the following variables were significantly associated with the platelet count: age, alanine aminotransferase (ALT), direct bilirubin, total bilirubin, IPF, international normalized ratio (INR), spleen size, vWF, glycocalicin, fibrosis stage on liver biopsy, and TE (P-values all < 0.05). A multivariable model determined that imputed TE score, TPO, IPF, and spleen size were independently associated with the platelet count (P-values all < 0.05). Conclusions: The platelet count in CHC is significantly associated with fibrosis, TPO level, IPF, and spleen size. Our findings challenge the proposed mechanism of decreased TPO levels or decreased bone marrow production of platelets as a cause of thrombocytopenia in CHC. Future studies focusing on the effects of fibrosis and splenomegaly on platelets may shed more light on the pathophysiology of thrombocytopenia in patients with CHC. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Tana, Michele M.; Zhao, Xiongce; Bradshaw, Alyson; Moon, Mi Sun; Page, Sandy; Turner, Tiffany; Rivera, Elenita; Heller, Theo] NIDDKD, Liver Dis Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Tana, Michele M.] Univ Calif San Francisco, Div Gastroenterol, UCSF Liver Ctr, San Francisco, CA 94143 USA. [Kleiner, David E.] NCI, NIH, Bethesda, MD 20892 USA. RP Tana, MM (reprint author), NIDDKD, Liver Dis Branch, Div Intramural Res, NIH, 9000 Rockville Pike,Bldg 10,Rm 9B16, Bethesda, MD 20892 USA. EM tanam@medsfgh.ucsf.edu FU Intramural Division of the National Institute of Diabetes and Digestive and Kidney Diseases; National Cancer Institute, National Institutes of Health FX This work was funded by the Intramural Division of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute, National Institutes of Health. NR 26 TC 5 Z9 5 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD MAY PY 2015 VL 135 IS 5 BP 823 EP 828 DI 10.1016/j.thromres.2015.02.010 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CG7NP UT WOS:000353490800009 PM 25728497 ER PT J AU Singh, SK Lupo, PJ Scheurer, ME Kennedy, AE Okcu, MF Dorak, MT AF Singh, Sandeep K. Lupo, Philip J. Scheurer, Michael E. Kennedy, Amy E. Okcu, M. Fatih Dorak, Mehmet Tevfik TI HLA REGION CONTRIBUTES TO THE GENDER DIFFERENTIAL IN CHILDHOOD LEUKAEMIA RISK SO TISSUE ANTIGENS LA English DT Meeting Abstract CT European-Federation-for-Immunogenetics Conference CY APR 26-29, 2015 CL Geneva, SWITZERLAND SP European Federat Immunogenet C1 [Singh, Sandeep K.] Florida Int Univ, Miami, FL 33199 USA. [Lupo, Philip J.; Scheurer, Michael E.; Okcu, M. Fatih] Baylor Coll Med, Houston, TX 77030 USA. [Kennedy, Amy E.] NCI, Bethesda, MD 20892 USA. [Dorak, Mehmet Tevfik] Liverpool Hope Univ, Liverpool, Merseyside, England. EM mtd3053@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-2815 EI 1399-0039 J9 TISSUE ANTIGENS JI Tissue Antigens PD MAY PY 2015 VL 85 IS 5 MA P26 BP 339 EP 339 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA CF9SN UT WOS:000352907000103 ER PT J AU Chaloupka, FJ Tauras, JA Strasser, JH Willis, G Gibson, JT Hartman, AM AF Chaloupka, Frank J. Tauras, John A. Strasser, Julia H. Willis, Gordon Gibson, James T. Hartman, Anne M. TI A comparison of alternative methods for measuring cigarette prices SO TOBACCO CONTROL LA English DT Article AB Background Government agencies, public health organisations and tobacco control researchers rely on accurate estimates of cigarette prices for a variety of purposes. Since the 1950s, the Tax Burden on Tobacco (TBOT) has served as the most widely used source of this price data despite its limitations. Purpose This paper compares the prices and collection methods of the TBOT retail-based data and the 2003 and 2006/2007 waves of the population-based Tobacco Use Supplement to the Current Population Survey (TUS-CPS). Methods From the TUS-CPS, we constructed multiple state-level measures of cigarette prices, including weighted average prices per pack (based on average prices for single-pack purchases and average prices for carton purchases) and compared these with the weighted average price data reported in the TBOT. We also constructed several measures of tax avoidance from the TUS-CPS self-reported data. Results For the 2003 wave, the average TUS-CPS price was 71 cents per pack less than the average TBOT price; for the 2006/2007 wave, the difference was 47 cents. TUS-CPS and TBOT prices were also significantly different at the state level. However, these differences varied widely by state due to tax avoidance opportunities, such as cross-border purchasing. Conclusions The TUS-CPS can be used to construct valid measures of cigarette prices. Unlike the TBOT, the TUS-CPS captures the effect of price-reducing marketing strategies, as well as tax avoidance practices and non-traditional types of purchasing. Thus, self-reported data like TUS-CPS appear to have advantages over TBOT in estimating the 'real' price that smokers face. C1 [Chaloupka, Frank J.] Univ Illinois, Inst Hlth Res & Policy, Dept Econ, Chicago, IL 60608 USA. [Tauras, John A.] Univ Illinois, Dept Econ, Chicago, IL 60608 USA. [Strasser, Julia H.; Willis, Gordon; Hartman, Anne M.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. [Gibson, James T.] Informat Management Serv Inc, Calverton, MD USA. RP Chaloupka, FJ (reprint author), Univ Illinois, Inst Hlth Res & Policy, 1747 W Roosevelt,Room 558, Chicago, IL 60608 USA. EM hartmana@mail.nih.gov FU National Cancer Institute [HHSN21200800697P] FX Funding support provided by the National Cancer Institute Contract #: HHSN21200800697P. NR 14 TC 1 Z9 1 U1 2 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 EI 1468-3318 J9 TOB CONTROL JI Tob. Control PD MAY PY 2015 VL 24 IS 3 BP 269 EP 274 DI 10.1136/tobaccocontrol-2013-051320 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CG5NA UT WOS:000353337500016 PM 24365701 ER PT J AU Gilman, JM Smith, AR Bjork, JM Ramchandani, VA Momenan, R Hommer, DW AF Gilman, Jodi M. Smith, Ashley R. Bjork, James M. Ramchandani, Vijay A. Momenan, Reza Hommer, Daniel W. TI Cumulative gains enhance striatal response to reward opportunities in alcohol-dependent patients SO ADDICTION BIOLOGY LA English DT Article DE Alcoholism; reward; ventral striatum ID DECISION-MAKING DEFICITS; RISK-TAKING; DETOXIFIED ALCOHOLICS; FUTURE CONSEQUENCES; ANTERIOR CINGULATE; PREFRONTAL CORTEX; DOPAMINE NEURONS; WORKING-MEMORY; GAMBLING TASK; NEURAL BASIS AB Substance use disorder is characterized by a transition from volitional to compulsive responding for drug reward. A possible explanation for this transition may be that alcohol-dependent patients (ADP) show a general propensity for a history of rewarded instrumental responses, and these rewarded responses may boost the activation of motivational neurocircuitry for additional reward. Brain imaging studies of decision-making have demonstrated that ADP relative to controls (CON) often show altered neural activation in response to anticipating and receiving rewards, but the majority of studies have not investigated how past performance affects activation. A potential exists for ADP to show increased sensitivity to reward as a function of reward delivery history. In the current study, we used functional magnetic resonance imaging to investigate the neural correlates of risky decision-making in ADP (n=18) and CON (n=18) while they played a two-choice monetary risk-taking game. In addition to investigating general neural recruitment by risky decision-making, we also modeled each participant's running total of monetary earnings in order to determine areas of activation that correlated with cumulative reward. We found that ADP and CON showed few differences in behavior or in mesolimbic activation by choice for, and receipt of, risky gains. However, when including a cumulative-earnings covariate, ADP exhibited heightened striatal activation that correlated with total earnings during the choice event in the task. The heightened contextual sensitivity of striatal responses to cumulative earnings in ADP may represent a general neurobiological affective substrate for development of automatized instrumental behavior. C1 [Gilman, Jodi M.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. [Smith, Ashley R.] Temple Univ, Dept Psychol, Neurocognit Lab, Philadelphia, PA 19122 USA. [Bjork, James M.] NIDA, Clin Neurosci Branch, Div Clin Neurosci & Behav Res, Bethesda, MD 20892 USA. [Ramchandani, Vijay A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Momenan, Reza; Hommer, Daniel W.] NIAAA, Sect Brain Electrophysiol & Imaging, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. RP Gilman, JM (reprint author), Massachusetts Gen Hosp, MGH Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA. EM jgilman1@partners.org OI Bjork, James/0000-0003-0593-3291 FU NIDA NIH HHS [K01 DA034093, L30 DA034327] NR 65 TC 3 Z9 3 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 EI 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD MAY PY 2015 VL 20 IS 3 BP 580 EP 593 DI 10.1111/adb.12147 PG 14 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA CF6FK UT WOS:000352652200015 PM 24754451 ER PT J AU Papadopoulos, NG Bernstein, JA Demoly, P Dykewicz, M Fokkens, W Hellings, PW Peters, AT Rondon, C Togias, A Cox, LS AF Papadopoulos, N. G. Bernstein, J. A. Demoly, P. Dykewicz, M. Fokkens, W. Hellings, P. W. Peters, A. T. Rondon, C. Togias, A. Cox, L. S. TI Phenotypes and endotypes of rhinitis and their impact on management: a PRACTALL report SO ALLERGY LA English DT Article DE classification; endotypes; phenotypes; rhinitis; treatment ID SEASONAL ALLERGIC RHINITIS; AQUEOUS NASAL SPRAY; PLACEBO-CONTROLLED TRIAL; IMMUNOLOGY/PRACTALL CONSENSUS REPORT; INTRANASAL CORTICOSTEROID-THERAPY; NONINFECTIOUS PERENNIAL RHINITIS; LEUKOTRIENE RECEPTOR ANTAGONISTS; EXACERBATED RESPIRATORY-DISEASE; NONALLERGIC VASOMOTOR RHINITIS; ENVIRONMENTAL EXPOSURE CHAMBER AB Rhinitis is an umbrella term that encompasses many different subtypes, several of which still elude complete characterization. The concept of phenotyping, being the definition of disease subtypes on the basis of clinical presentation, has been well established in the last decade. Classification of rhinitis entities on the basis of phenotypes has facilitated their characterization and has helped practicing clinicians to efficiently approach rhinitis patients. Recently, the concept of endotypes, that is, the definition of disease subtypes on the basis of underlying pathophysiology, has emerged. Phenotypes/endotypes are dynamic, overlapping, and may evolve into one another, thus rendering clear-cut definitions difficult. Nevertheless, a phenotype-/endotype-based classification approach could lead toward the application of stratified and personalized medicine in the rhinitis field. In this PRACTALL document, rhinitis phenotypes and endotypes are described, and rhinitis diagnosis and management approaches focusing on those phenotypes/endotypes are presented and discussed. We emphasize the concept of control-based management, which transcends all rhinitis subtypes. C1 [Papadopoulos, N. G.] Univ Manchester, Inst Human Dev, Ctr Paediat & Child Hlth, Manchester, Lancs, England. [Papadopoulos, N. G.] Univ Athens, Dept Allergy, Paediat Clin 2, Athens, Greece. [Bernstein, J. A.] Univ Cincinnati, Dept Internal Med, Cincinnati, OH USA. [Demoly, P.] Univ Hosp Montpellier, Dept Allergy, Montpellier, France. [Dykewicz, M.] St Louis Univ, Sch Med, Sect Allergy & Clin Immunol, St Louis, MO USA. [Fokkens, W.] Univ Amsterdam, Acad Med Ctr, Dept Otorhinolaryngol, NL-1105 AZ Amsterdam, Netherlands. [Hellings, P. W.] Univ Hosp Leuven, Dept Otorhinolaryngol, Leuven, Belgium. [Peters, A. T.] Northwestern Univ, Dept Med, Div Allergy Immunol, Feinberg Sch Med, Chicago, IL 60611 USA. [Rondon, C.] Hosp Carlos Haya, Serv Alergol, Malaga, Spain. [Togias, A.] NIAID, NIH, Bethesda, MD 20892 USA. [Cox, L. S.] Nova SE Univ, Davie, FL USA. RP Papadopoulos, NG (reprint author), Royal Manchester Childrens Hosp, 5th Floor Res, Manchester M13 9WL, Lancs, England. EM Nikolaos.Papadopoulos@manchester.ac.uk FU European Academy of Allergy and Clinical Immunology; American Academy of Allergy, Asthma and Immunology FX This work has been funded by the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology. NR 305 TC 23 Z9 25 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD MAY PY 2015 VL 70 IS 5 BP 474 EP 494 DI 10.1111/all.12573 PG 21 WC Allergy; Immunology SC Allergy; Immunology GA CF4RJ UT WOS:000352538200002 PM 25620381 ER PT J AU Schindler-Ruwisch, J Augustson, E Lynch, K Patrick, H AF Schindler-Ruwisch, Jennifer Augustson, Erik Lynch, Krystal Patrick, Heather TI BMI and Smoking: Interrelated Factors among Cessation Website Users SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE body mass index; obesity; cigarette smoking ID BODY-WEIGHT; METABOLIC SYNDROME; UNITED-STATES; OBESITY; POPULATION; MORTALITY; ADULTS; RISK AB Objective: To investigate the relationship between body mass index (BMI) and smoking. Methods: Participants (N = 2243) provided demographic, height, weight, smoking information through a survey conducted on smokefree.gov and women. smokefree.gov websites. Analysis assessed associations among BMI, smoking status, and cigarettes smoked per day (CPD). Results: The average (SD) BMI of never, former, intermittent, and daily smokers was 26.3 (6.2), 27.9 (6.5), 27.4 (6.7) and 28.1 (6.8) respectively. Daily (31.2%) and former (32.3%) were more likely to be to be obese compared to never (22.0%) and intermittent (26.1%) smokers. Odds of being obese increased with number of CPD adjusting for potential confounders. Conclusions: Smokers may currently have BMIs similar to the general population. BMI and CPD were positively correlated. C1 [Schindler-Ruwisch, Jennifer; Lynch, Krystal] BLH Technol Inc, Rockville, MD USA. [Augustson, Erik] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD 20852 USA. [Patrick, Heather] LiveHealthier Inc, Prod Dev, Bethesda, MD USA. RP Augustson, E (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD 20852 USA. EM augustse@mail.nih.gov FU Federal funds from the National Cancer Institute, National Institutes of Health, US Department of Health and Human Services; [HHSN261201000043C] FX This project has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, US Department of Health and Human Services; this analysis was funded partially under Contract No. HHSN261201000043C. NR 22 TC 0 Z9 0 U1 3 U2 3 PU PNG PUBLICATIONS PI OAK RIDGE PA 2205-K OAK RIDGE RD, #115, OAK RIDGE, NC 27310 USA SN 1945-7359 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD MAY PY 2015 VL 39 IS 3 BP 330 EP 337 DI 10.5993/AJHB.39.3.5 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CF5UD UT WOS:000352621700005 PM 25898436 ER PT J AU Hesse, BW Moser, RP Riley, WT AF Hesse, Bradford W. Moser, Richard P. Riley, William T. TI From Big Data to Knowledge in the Social Sciences SO ANNALS OF THE AMERICAN ACADEMY OF POLITICAL AND SOCIAL SCIENCE LA English DT Article DE big data; data visualization; integrative data analysis; informatics ID HEALTH; COMMUNICATION; NETWORKS; PROMISE; SYSTEM AB One of the challenges associated with high-volume, diverse datasets is whether synthesis of open data streams can translate into actionable knowledge. Recognizing that challenge and other issues related to these types of data, the National Institutes of Health developed the Big Data to Knowledge or BD2K initiative. The concept of translating big data to knowledge is important to the social and behavioral sciences in several respects. First, a general shift to data-intensive science will exert an influence on all scientific disciplines, but particularly on the behavioral and social sciences given the wealth of behavior and related constructs captured by big data sources. Second, science is itself a social enterprise; by applying principles from the social sciences to the conduct of research, it should be possible to ameliorate some of the systemic problems that plague the scientific enterprise in the age of big data. We explore the feasibility of recalibrating the basic mechanisms of the scientific enterprise so that they are more transparent and cumulative; more integrative and cohesive; and more rapid, relevant, and responsive. C1 [Hesse, Bradford W.] Natl Canc Inst, Training, Bethesda, MD 20892 USA. [Hesse, Bradford W.] Natl Canc Inst, Hlth Commun & Informat Res Branch, Behav Res Program, Bethesda, MD USA. [Moser, Richard P.] Natl Canc Inst, Sci Res & Technol Branch, Behav Res Program, Bethesda, MD USA. [Riley, William T.] Natl Inst Hlth, Off Behav & Social Sci Res, Bethesda, MD USA. [Riley, William T.] Natl Canc Inst, Sci Res & Technol Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD USA. RP Hesse, BW (reprint author), Natl Canc Inst, Training, Bethesda, MD 20892 USA. RI Trivedi, Kruti/E-7558-2015; OI Hesse, Bradford/0000-0003-1142-1161 FU Intramural NIH HHS [Z99 CA999999] NR 54 TC 7 Z9 7 U1 13 U2 51 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0002-7162 EI 1552-3349 J9 ANN AM ACAD POLIT SS JI Ann. Am. Acad. Polit. Soc. Sci. PD MAY PY 2015 VL 659 IS 1 BP 16 EP 32 DI 10.1177/0002716215570007 PG 17 WC Political Science; Social Sciences, Interdisciplinary SC Government & Law; Social Sciences - Other Topics GA CF8EV UT WOS:000352789600002 PM 26294799 ER PT J AU Jin, XT Xu, Q Champion, K Kruth, HS AF Jin, Xueting Xu, Qing Champion, Keith Kruth, Howard S. TI Endotoxin contamination of apolipoprotein A-I: Effect on macrophage proliferation - A cautionary tale SO ATHEROSCLEROSIS LA English DT Article DE Endotoxin; Macrophages; Cell proliferation; Apolipoproteins; Atherosclerosis ID LIPOPOLYSACCHARIDE-BINDING PROTEIN; HIGH-DENSITY-LIPOPROTEINS; NEUTRALIZATION; PEPTIDES; INACTIVATION; INHIBITION; EXPRESSION; INDUCTION; CYTOKINE; CAPACITY AB This technical report addresses the problem of endotoxin contamination of apolipoprotein reagents. Using a bromodeoxyuridine incorporation cell proliferation assay, we observed that human plasma ApoA-I as low as 1 mu g/ml resulted in a >90% inhibition in macrophage proliferation. However, not all ApoA-I from different sources showed this effect. We considered the possibility that endotoxin contamination of the apolipoproteins contributed to the differential inhibition of macrophage cell proliferation. Endotoxin alone very potently inhibited macrophage proliferation (0.1 ng/ml inhibited macrophage proliferation >90%). Measurement of endotoxin levels in the apolipoprotein products, including an analysis of free versus total endotoxin, the latter which included endotoxin that was masked due to binding to protein, suggested that free endotoxin mediated inhibition of macrophage proliferation. Despite the use of an advanced endotoxin removal procedure and agents commonly used to inhibit endotoxin action, the potency of endotoxin precluded successful elimination of endotoxin effect. Our findings show that endotoxin contamination can significantly influence apparent apolipoprotein-mediated cell effects (or effects of any other biological products), especially when these products are tested on highly endotoxin-sensitive cells, such as macrophages. Published by Elsevier Ireland Ltd. C1 [Jin, Xueting; Xu, Qing; Kruth, Howard S.] NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. [Champion, Keith] BioDtech Inc, Birmingham, AL 35209 USA. RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, Bldg 10,Room 5N-113,10 Ctr Dr MSC 1422, Bethesda, MD 20892 USA. EM kruthh@nhlbi.nih.gov FU Intramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health FX We thank the Department of Transfusion Medicine, Clinical Center, National Institutes of Health, for providing elutriated monocytes. The Intramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health supported this work. NR 22 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 2015 VL 240 IS 1 BP 121 EP 124 DI 10.1016/j.atherosclerosis.2015.03.007 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CF6YR UT WOS:000352703400019 PM 25778625 ER PT J AU Kim, CHJ Mitchell, JB Bursill, CA Sowers, AL Thetford, A Cook, JA van Reyk, DM Davies, MJ AF Kim, Christine H. J. Mitchell, James B. Bursill, Christina A. Sowers, Anastasia L. Thetford, Angela Cook, John A. van Reyk, David M. Davies, Michael J. TI The nitroxide radical TEMPOL prevents obesity, hyperlipidaemia, elevation of inflammatory cytokines, and modulates atherosclerotic plaque composition in apoE(-/-) mice SO ATHEROSCLEROSIS LA English DT Article DE TEMPOL; Nitroxide; Atherosclerosis; Cardiovascular disease; Lipid; Inflammatory cytokines; Adipokines ID NECROSIS-FACTOR-ALPHA; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; MESSENGER-RNA; NITRIC-OXIDE; MYELOPEROXIDASE; INHIBITION; EXPRESSION; CELLS; RATS AB Objective: The nitroxide compound TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl radical) has been shown to prevent obesity-induced changes in adipokines in cell and animal systems. In this study we investigated whether supplementation with TEMPOL inhibits inflammation and atherosclerosis in apoE(-/-) mice fed a high fat diet (HFD). Methods: ApoE(-/-) mice were fed for 12 weeks on standard chow diet or a high-fat diet. Half the mice were supplemented with 10 mg/g TEMPOL in their food. Plasma samples were analysed for triglycerides, cholesterol, low-and high-density lipoprotein cholesterol, inflammatory cytokines and markers (inter-leukin- 6, IL-6; monocyte-chemotactic protein, MCP-1; myeloperoxidase, MPO; serum amyloid A, SAA; adiponectin; leptin). Plaques in the aortic sinus were analysed for area, and content of collagen, lipid, macrophages and smooth muscle cells. Results: High fat feeding resulted in marked increases in body mass and plasma lipid levels. Dietary TEMPOL decreased both parameters. In the high-fat-fed mice significant elevations in plasma lipid levels and the inflammatory markers IL-6, MCP-1, MPO, SAA were detected, along with an increase in leptin and a decrease in adiponectin. TEMPOL supplementation reversed these effects. When compared to HFD-fed mice, TEMPOL supplementation increased plaque collagen content, decreased lipid content and increased macrophage numbers. Conclusions: These data indicate that in a well-established model of obesity-associated hyperlipidaemia and atherosclerosis, TEMPOL had a significant impact on body mass, atherosclerosis, hyperlipidaemia and inflammation. TEMPOL may therefore be of value in suppressing obesity, metabolic disorders and increasing atherosclerotic plaque stability. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Kim, Christine H. J.; Davies, Michael J.] Heart Res Inst, Free Radical Grp, Newtown, NSW 2042, Australia. [Kim, Christine H. J.; Bursill, Christina A.; Davies, Michael J.] Univ Sydney, Fac Med, Sydney, NSW 2006, Australia. [Mitchell, James B.; Sowers, Anastasia L.; Thetford, Angela; Cook, John A.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Bursill, Christina A.] Heart Res Inst, Immunobiol Grp, Newtown, NSW 2042, Australia. [van Reyk, David M.] Univ Technol Sydney, Fac Sci, Broadway, NSW 2007, Australia. [Davies, Michael J.] Univ Copenhagen, Panum Inst, Dept Biomed Sci, DK-2200 Copenhagen N, Denmark. RP Davies, MJ (reprint author), Univ Copenhagen, Panum Inst, Dept Biomed Sci, Bldg 4-5,Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. EM christinehjkim@gmail.com; jbm@helix.nih.gov; bursillc@hri.org.au; stasia@mail.nih.gov; thetforda@mail.nih.gov; cook@helix.nih.gov; david.vanreyk@uts.edu.au; davies@sund.ku.dk RI Davies, Michael/H-4939-2011 OI Davies, Michael/0000-0002-5196-6919 FU Australian Research Council (ARC Centres of Excellence and Discovery Programs) [CE0561607, DP0988311]; Community Grant; University Postgraduate Award from the University of Sydney FX This work was supported by grants from the Australian Research Council (ARC Centres of Excellence and Discovery Programs, CE0561607 and DP0988311 respectively) and a JB Were Community Grant. Christine HJ Kim was a recipient of a University Postgraduate Award from the University of Sydney. NR 50 TC 3 Z9 4 U1 1 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 2015 VL 240 IS 1 BP 234 EP 241 DI 10.1016/j.atherosclerosis.2015.03.012 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CF6YR UT WOS:000352703400037 PM 25818249 ER PT J AU Tian, Q Glynn, NW Erickson, KI Aizenstein, HJ Simonsick, EM Yaffe, K Harris, TB Kritchevsky, SB Boudreau, RM Newman, AB Lopez, OL Saxton, J Rosano, C AF Tian, Qu Glynn, Nancy W. Erickson, Kirk I. Aizenstein, Howard J. Simonsick, Eleanor M. Yaffe, Kristine Harris, Tamara B. Kritchevsky, Stephen B. Boudreau, Robert M. Newman, Anne B. Lopez, Oscar L. Saxton, Judith Rosano, Caterina CA Hlth ABC Study TI Objective measures of physical activity, white matter integrity and cognitive status in adults over age 80 SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE White matter integrity; Diffusion tensor imaging; SenseWear Armband; Very old adults ID LIFE-STYLE INTERVENTIONS; OLDER-ADULTS; CARDIORESPIRATORY FITNESS; SUBSEQUENT DISABILITY; ENERGY-EXPENDITURE; HEALTHY SENIORS; AEROBIC FITNESS; AGING BRAIN; GAIT SPEED; MR-IMAGES AB The neuroprotective effects of physical activity (PA) are consistently shown in older adults, but the neural substrates, particularly in white matter (WM), are understudied, especially in very old adults with the fastest growth rate and the highest risk of dementia. This study quantified the association between PA and WM integrity in adults over SO. The moderating effects of cardiometabolic conditions, physical functional limitations and WM hyperintensities were also examined, as they can affect PA and brain integrity. Fractional anisotropy (FA) from normal-appearing WM via diffusion tensor imaging and WM hyperintensities were obtained in 90 participants (mean age =87.4,51.1% female, 55.6% white) with concurrent objective measures of steps, active energy expenditure (AEE in kcal), duration (min), and intensity (metabolic equivalents, METs) via SenseWear Armband. Clinical adjudication of cognitive status, prevalence of stroke and diabetes, systolic blood pressure, and gait speed were assessed at time of neuroimaging. Participants were on average sedentary (mean +/- SD/day: 1766 +/- 1345 steps, 202 +/- 311 kcal, 211 +/- 39 min, 1.8 +/- 1.1 METs). Higher steps, AEE and duration, but not intensity, were significantly associated with higher FA. Associations were localized in frontal and temporal areas. Moderating effects of cardiometabolic conditions, physical functional limitations, and WM hyperintensities were not significant. Neither FA nor PA was related to cognitive status. Older adults with a sedentary lifestyle and a wide range of cardiometabolic conditions and physical functional limitations, displayed higher WM integrity in relation to higher PA. Studies of very old adults to quantify the role of PA in reducing dementia burden via WM integrity are warranted. (C) 2015 Elsevier B.V. All rights reserved. C1 [Tian, Qu; Glynn, Nancy W.; Boudreau, Robert M.; Newman, Anne B.; Rosano, Caterina] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Erickson, Kirk I.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Aizenstein, Howard J.; Saxton, Judith] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Kritchevsky, Stephen B.] Wake Forest Sch Med, Sticht Ctr Aging, Sect Gerontol & Geriatr, Med, Winston Salem, NC USA. [Lopez, Oscar L.; Saxton, Judith] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. RP Tian, Q (reprint author), 251 Bayview Blvd,Suite 100,Rm 04B316, Baltimore, MD 21224 USA. EM qu.tian@nih.gov RI Newman, Anne/C-6408-2013; Dey, Kamalesh/E-6568-2017; OI Newman, Anne/0000-0002-0106-1150; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010; Boudreau, Robert/0000-0003-0162-5187; Glynn, Nancy/0000-0003-2265-0162 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, NO1-AG-6-2106, K23-AG028966-01]; NIA [R01-AG028050, R01-AG029232, P30-AG024827]; NINR [R01-NR012459]; 8th Annual Department of Epidemiology Small Grant program, University of Pittsburgh; Intramural Research Program of the NIH National Institute on Aging FX This research was supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101, N01-AG-6-2103, NO1-AG-6-2106, K23-AG028966-01; NIA grants R01-AG028050, R01-AG029232, P30-AG024827, and NINR grant R01-NR012459, and supported by 8th Annual Department of Epidemiology Small Grant program, University of Pittsburgh. This research was supported in part by the Intramural Research Program of the NIH National Institute on Aging. NR 46 TC 4 Z9 4 U1 3 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 EI 1872-7549 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD MAY 1 PY 2015 VL 284 BP 51 EP 57 DI 10.1016/j.bbr.2015.01.045 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CF6NB UT WOS:000352672300007 PM 25655514 ER PT J AU Radulescu, E Chen, Q Mattay, VS Callicott, JH Zink, CF Goldberg, TE Ursini, G Kleinman, JE Weinberger, DR AF Radulescu, Eugenia Chen, Qiang Mattay, Venkata S. Callicott, Joseph H. Zink, Caroline F. Goldberg, Terry E. Ursini, Gianluca Kleinman, Joel E. Weinberger, Daniel R. TI Selective Effects of the GWAS DRD2 Locus Associated with Schizophrenia on the Prefrontal-nigro-striatal Circuits Supporting the Executive Functions SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE DRD2; fMRI; cortico-nigro-striatal circuits; working memory; connectivity C1 [Radulescu, Eugenia; Chen, Qiang; Mattay, Venkata S.; Zink, Caroline F.; Ursini, Gianluca; Kleinman, Joel E.; Weinberger, Daniel R.] Lieber Inst Brain Dev, Clin Sci Div, Baltimore, MD USA. [Callicott, Joseph H.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Goldberg, Terry E.] Feinstein Inst Med Res, Litwin Zucker Res Ctr, Manhasset, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 9 BP 3S EP 4S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500010 ER PT J AU Ursini, G Marenco, S Chen, Q Straub, RE Punzi, G Weinberger, DR AF Ursini, Gianluca Marenco, Stefano Chen, Qiang Straub, Richard E. Punzi, Giovanna Weinberger, Daniel R. TI GWAS Derived Risk Profile Score Is Associated with Schizophrenia Only in Individuals Exposed to Obstetric Complications SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE schizophrenia; obstetric complications; GWAS derived Risk Profile Scores; neurodevelopment; gene-environment interaction C1 [Ursini, Gianluca; Chen, Qiang; Straub, Richard E.; Punzi, Giovanna; Weinberger, Daniel R.] Lieber Inst Brain Dev, Div Clin Sci, Baltimore, MD USA. [Ursini, Gianluca; Punzi, Giovanna] Aldo Moro Univ, Dept Basic Med Sci Neurosci & Sense Organs, Grp Psychiat Neurosci, Bari, Italy. [Marenco, Stefano] NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 0 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 10 BP 4S EP 4S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500011 ER PT J AU Tseng, WL Brotman, MA Deveney, CM Moroney, E Machlin, L Towbin, K Pine, DS Leibenluft, E AF Tseng, Wan-Ling Brotman, Melissa A. Deveney, Christen M. Moroney, Elizabeth Machlin, Laura Towbin, Kenneth Pine, Daniel S. Leibenluft, Ellen TI Neural Correlates of Irritability across Diagnoses: Categorical and Dimensional Approaches SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE irritability; DMDD; fMRI; categorical; dimensional C1 [Tseng, Wan-Ling; Brotman, Melissa A.; Moroney, Elizabeth; Machlin, Laura; Towbin, Kenneth; Pine, Daniel S.; Leibenluft, Ellen] NIMH, Emot & Dev Branch, Bethesda, MD 20892 USA. [Deveney, Christen M.] Wellesley Coll, Dept Psychol, Wellesley, MA 02181 USA. RI Brotman, Melissa/H-7409-2013 NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 31 BP 11S EP 12S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500032 ER PT J AU Ahn, K Mentch, FD Kao, C Hakonarson, H Rapoport, JL AF Ahn, Kwangmi Mentch, Frank D. Kao, Chally Hakonarson, Hakon Rapoport, Judith L. TI Overall Clinical Impairment Associated with Rare Copy Number Variants (CNVs) Associated with Neurodevelopmental Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE copy number variants; neurodevelopmental disorders C1 [Ahn, Kwangmi; Rapoport, Judith L.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Mentch, Frank D.; Kao, Chally; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 49 BP 19S EP 19S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500050 ER PT J AU Perez-Rodriguez, MM New, AS Goldstein, KE Yuan, QP Zhou, ZF Chowdhury, S Shen, PH Rothstein, E Rimsky, LS Koenigsberg, HW Goodman, M Hodgkinson, C Goldman, D Hazlett, E Siever, LJ AF Perez-Rodriguez, M. Mercedes New, Antonia S. Goldstein, Kim E. Yuan, Qiaoping Zhou, Zhifeng Chowdhury, Salwa Shen, Pei-Hong Rothstein, Ethan Rimsky, Liza S. Koenigsberg, Harold W. Goodman, Marianne Hodgkinson, Colin Goldman, David Hazlett, Erin Siever, Larry J. TI Converging Multimodal Evidence for Social Cognitive Abnormalities in Borderline Personality Disorder: Models, Mechanisms and Novel Therapies SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Borderline Personality Disorder; Social Cognition; Oxytocin; fMRI; BDNF C1 [Perez-Rodriguez, M. Mercedes; New, Antonia S.; Goldstein, Kim E.; Chowdhury, Salwa; Rothstein, Ethan; Rimsky, Liza S.; Koenigsberg, Harold W.; Goodman, Marianne; Hazlett, Erin; Siever, Larry J.] Icahn Sch Med Mt Sinai, Psychiat, New York, NY 10029 USA. [Yuan, Qiaoping; Zhou, Zhifeng; Shen, Pei-Hong; Hodgkinson, Colin; Goldman, David] NIAAA, Lab Neurogenet, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 75 BP 29S EP 29S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500076 ER PT J AU Michalska, KJ Ivie, EJ Shechner, T Pine, DS AF Michalska, Kalina J. Ivie, Elizabeth J. Shechner, Tomer Pine, Daniel S. TI Autonomic Modulation of Neural Responses During Fear Extinction Recall SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE fear conditioning; functional magnetic resonance imaging; skin conductance; extinction recall C1 [Michalska, Kalina J.; Ivie, Elizabeth J.; Pine, Daniel S.] NIH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. [Shechner, Tomer] Univ Haifa, Dept Psychol, IL-31999 Haifa, Israel. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 124 BP 45S EP 45S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500117 ER PT J AU Szczepanik, J Nugent, A Zarate, C Furey, M AF Szczepanik, Joanna Nugent, Allison Zarate, Carlos Furey, Maura TI Amygdala Response to Selective Emotion Processing Conditions at Baseline Predicts Antidepressant Treatment Response to Scopolamine in Major Depressive Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE major depression; amygdala; fMRI; scopolamine; emotional processing C1 [Szczepanik, Joanna; Nugent, Allison; Zarate, Carlos] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Szczepanik, Joanna] Univ Maryland, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA. [Furey, Maura] Johnson & Johnson, Neurosci Biomarkers, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 194 BP 73S EP 73S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500187 ER PT J AU Brouwer, RM Glahn, DC Hibar, DP Hua, X Jahanshad, N Franz, CE Koenis, MMG Mather, K Swagerman, S Thalamuthu, A Wen, W Boomsma, DI Gilmore, JH Gogtay, N Kahn, RS Kremen, WS Sachdev, PS Wright, MJ Thompson, PM Pol, HEH AF Brouwer, Rachel M. Glahn, David C. Hibar, Derrek P. Hua, Xue Jahanshad, Neda Franz, Carol E. Koenis, Marinka M. G. Mather, Karen Swagerman, Suzanne Thalamuthu, Anbupalam Wen, Wei Boomsma, Dorret I. Gilmore, John H. Gogtay, Nitin Kahn, Rene S. Kremen, William S. Sachdev, Perminder S. Wright, Margie J. Thompson, Paul M. Pol, Hilleke E. Hulshoff TI Genetic Influences on Brain Plasticity: First Results of the ENIGMA Plasticity Working Group SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Imaging; Genetics; Plasticity; heritability C1 [Brouwer, Rachel M.; Koenis, Marinka M. G.; Kahn, Rene S.; Pol, Hilleke E. Hulshoff] Univ Med Ctr Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands. [Glahn, David C.] Yale Univ Med, Dept Psychiat, New Haven, CT USA. [Hibar, Derrek P.; Hua, Xue; Jahanshad, Neda; Thompson, Paul M.] USC Keck Sch Med, Inst Neuroimaging & Informat, Imaging Genet Ctr, Los Angeles, CA USA. [Franz, Carol E.; Kremen, William S.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Mather, Karen; Thalamuthu, Anbupalam; Wen, Wei; Sachdev, Perminder S.] Univ New S Wales, Dept Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia. [Swagerman, Suzanne; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Gilmore, John H.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Gogtay, Nitin] NIMH, Dept Psychiat, NIH, Bethesda, MD 20892 USA. [Wright, Margie J.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. RI Karen, Mather/O-9795-2016 OI Karen, Mather/0000-0003-4143-8941 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 223 BP 84S EP 84S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500216 ER PT J AU Friedman, LA Anvari, AA Kasoff, L Ahn, K Rapoport, JL AF Friedman, Lisa A. Anvari, Afsoon A. Kasoff, Lauren Ahn, Kwangmi Rapoport, Judith L. TI 1q21 Microduplications in Two Pediatric Patients with Neurodevelopmental Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Copy number variation; Neurodevelopmental disorders; Genetics C1 [Friedman, Lisa A.; Anvari, Afsoon A.; Kasoff, Lauren; Ahn, Kwangmi; Rapoport, Judith L.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 232 BP 88S EP 88S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500225 ER PT J AU Bonne, O Gill, J Lerner, A Nugent, AC Vythilingam, M Neumeister, A Drevets, WC AF Bonne, Omer Gill, Jessica Lerner, Alicja Nugent, Allison C. Vythilingam, Meena Neumeister, Alexander Drevets, Wayne C. TI Altered Cerebral gamma-Amniobutyric Acid Type A-Benzodiazapine Receptor Binding in PTSD Determined by [11C] Flumazenil Positron Emission Tomography SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE PTSD; PET; GABA-A; DMN C1 [Bonne, Omer] Hadassah Univ Hosp, Psychiat, IL-91120 Jerusalem, Israel. [Gill, Jessica] NINR, NIH, Bethesda, MD 20892 USA. [Lerner, Alicja] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Nugent, Allison C.] NIH, Branch Experiemental Therapeut, Bethesda, MD 20892 USA. [Vythilingam, Meena] Deployment Hlth Clin Ctr, Clin Sci & Translat, Chevy Chase, MD USA. [Neumeister, Alexander] NYU, Langone Med Ctr, Psychiat & Radiol, New York, NY USA. [Drevets, Wayne C.] Johnson & Johnson Inc, Janssen Res & Dev, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 258 BP 99S EP 99S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500251 ER PT J AU Park, MTM Raznahan, A Shaw, P Gogtay, N Chakravarty, MM AF Park, Min Tae M. Raznahan, Armin Shaw, Philip Gogtay, Nitin Chakravarty, M. Mallar TI Shared Cerebellar Phenotypes in Autism Spectrum Disorders and Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Cerebellum; Autism; Schizophrenia; MRI C1 [Park, Min Tae M.; Chakravarty, M. Mallar] Douglas Mental Hlth Univ Inst, Cerebral Imaging Ctr, Montreal, PQ, Canada. [Raznahan, Armin; Gogtay, Nitin] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Shaw, Philip] NHGRI, Sect Neurobehav Clin Res, Social & Behav Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 268 BP 103S EP 104S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500261 ER PT J AU Saha, D Yan, H Zhang, LL Muse, T Chen, Q Zhang, FY Mattay, VS Yue, WH Zhang, D Weinberger, DR Tan, HY AF Saha, Debjani Yan, Hao Zhang, Lanlan Muse, Tim Chen, Qiang Zhang, Fengyu Mattay, Venkata S. Yue, Weihua Zhang, Dai Weinberger, Daniel R. Tan, Hao Yang TI Genetic Risk for Schizophrenia During Working Memory Computation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE schizophrenia; computational working memory; siblings; dlpfc C1 [Saha, Debjani; Muse, Tim; Chen, Qiang; Zhang, Fengyu; Mattay, Venkata S.; Weinberger, Daniel R.; Tan, Hao Yang] Lieber Inst Brain Dev, Clin Sci, Baltimore, MD USA. [Yan, Hao; Zhang, Lanlan; Yue, Weihua; Zhang, Dai] Peking Univ, Inst Mental Hlth, Beijing 100871, Peoples R China. [Chen, Qiang; Mattay, Venkata S.; Weinberger, Daniel R.; Tan, Hao Yang] NIMH, Clin Brain Disorders Branch, NIH, Baltimore, MD USA. [Weinberger, Daniel R.; Tan, Hao Yang] Johns Hopkins Sch Med, Psychiat & Behav Sci, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 312 BP 122S EP 122S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500305 ER PT J AU Sastry, NV Ordonez, AE Moran, ME Greenstein, D Watsky, RE Luscher, ZI Shora, L Dillard-Broadnax, D Dillard-Broadnax, D Clasen, L Rapoport, J Gogtay, N AF Sastry, Nevin V. Ordonez, Anna E. Moran, Marcel E. Greenstein, Deanna Watsky, Rebecca E. Luscher, Zoe I. Shora, Lorie Dillard-Broadnax, Diane Dillard-Broadnax, Diane Clasen, Liv Rapoport, Judith Gogtay, Nitin TI Magnetic Resonance Imaging of the Fusiform Gyrus in Patients with Childhood-Onset Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE COS; Schizophrenia; Fusiform; MRI; Neuroimaging C1 [Sastry, Nevin V.; Ordonez, Anna E.; Moran, Marcel E.; Greenstein, Deanna; Watsky, Rebecca E.; Luscher, Zoe I.; Shora, Lorie; Dillard-Broadnax, Diane; Dillard-Broadnax, Diane; Clasen, Liv; Rapoport, Judith; Gogtay, Nitin] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 314 BP 122S EP 123S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500307 ER PT J AU Niciu, MJ Xu, AJ Lundin, NB Luckenbaugh, DA Ionescu, DF Richards, EM Voort, JLV Ballard, ED Brutsche, NE Machado-Vieira, R Zarate, CA AF Niciu, Mark J. Xu, Annie J. Lundin, Nancy B. Luckenbaugh, David A. Ionescu, Dawn F. Richards, Erica M. Voort, Jennifer L. Vande Ballard, Elizabeth D. Brutsche, Nancy E. Machado-Vieira, Rodrigo Zarate, Carlos A. TI Lithium and Valproate Levels Do Not Correlate with Ketamine's Antidepressant Efficacy in Treatment-Resistant Bipolar Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE ketamine; bipolar disorder; lithium; valproate; treatment-resistant depression C1 [Niciu, Mark J.; Lundin, Nancy B.; Luckenbaugh, David A.; Richards, Erica M.; Ballard, Elizabeth D.; Brutsche, Nancy E.; Machado-Vieira, Rodrigo; Zarate, Carlos A.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. [Xu, Annie J.] New York Med Coll, Valhalla, NY 10595 USA. [Ionescu, Dawn F.] Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Voort, Jennifer L. Vande] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 334 BP 130S EP 130S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500327 ER PT J AU Voort, JLV Ballard, ED Duncan, WC Luckenbaugh, DA Richards, EM Niciu, MJ Zarate, CA AF Voort, Jennifer L. Vande Ballard, Elizabeth D. Duncan, Wallace C. Luckenbaugh, David A. Richards, Erica M. Niciu, Mark J. Zarate, Carlos A. TI Antisuicidal Response after Ketamine Infusion Is Associated with Reduced Wakefulness in Treatment Resistant Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Ketamine; Suicide; Sleep; Treatment-Resistant Depression C1 [Voort, Jennifer L. Vande; Ballard, Elizabeth D.; Duncan, Wallace C.; Luckenbaugh, David A.; Richards, Erica M.; Niciu, Mark J.; Zarate, Carlos A.] NIMH, NIH, Bethesda, MD 20892 USA. [Voort, Jennifer L. Vande] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA. RI Niciu, Mark/J-1766-2014 OI Niciu, Mark/0000-0002-5612-3021 NR 0 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 333 BP 130S EP 130S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500326 ER PT J AU Calkins, ME Merikangas, KR Burstein, M Satterthwaite, T Wolf, D Moore, TM Ruparel, K Hakonarson, H Gur, RC Gur, RE AF Calkins, Monica E. Merikangas, Kathleen R. Burstein, Marcy Satterthwaite, Theodore Wolf, Daniel Moore, Tyler M. Ruparel, Kosha Hakonarson, Hakon Gur, Ruben C. Gur, Raquel E. TI Clinical Phenotypic Characterization of the Philadelphia Neurodevelopmental Cohort: Foundations for Integrative Investigations of Psychiatric Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE psychopathology; neurodevelopment; prospective C1 [Calkins, Monica E.] Univ Penn, Sch Med, Bethesda, MD USA. [Merikangas, Kathleen R.] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Burstein, Marcy] NIMH, Bethesda, MD 20892 USA. [Satterthwaite, Theodore; Wolf, Daniel; Moore, Tyler M.; Ruparel, Kosha; Gur, Ruben C.; Gur, Raquel E.] Univ Penn, Sch Med, Psychiat, Philadelphia, PA 19104 USA. [Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 805 BP 288S EP 289S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502006 ER PT J AU Pine, DS AF Pine, Daniel S. TI Development and Cognitive Neuroscience: Why Should I Care? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat C1 [Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 844 BP 303S EP 303S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502045 ER PT J AU Maynard, KR Sukumar, M Lu, B Tessarollo, L Schloesser, RJ Martinowich, K AF Maynard, Kristen R. Sukumar, Mahima Lu, Bai Tessarollo, Lino Schloesser, Robert J. Martinowich, Keri TI Promoter-Specific Production of BDNF Regulates Social Behaviors in Mice SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE BDNF; aggression; hypothalamus; social behavior; maternal care C1 [Maynard, Kristen R.; Sukumar, Mahima; Schloesser, Robert J.; Martinowich, Keri] Lieber Inst Brain Dev, Basic Sci, Baltimore, MD USA. [Lu, Bai] Tsingua Univ, Sch Med, Beijing, Peoples R China. [Tessarollo, Lino] NCI, Unit Mouse Genet, Frederick, MD 21701 USA. [Schloesser, Robert J.] Univ Maryland, Psychiat, Baltimore, MD 21201 USA. [Martinowich, Keri] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Martinowich, Keri] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 858 BP 308S EP 308S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502059 ER PT J AU Shaw, P AF Shaw, Philip TI Towards an Understanding of the Neural Processes Underpinning Persistence and Remission In ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE ADHD; Neuroimaging; Remission C1 [Shaw, Philip] NHGRI, NIH, Betehsda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 875 BP 314S EP 315S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502076 ER PT J AU Balderston, N Hale, E Ernst, M Grillon, C AF Balderston, Nicholas Hale, Elizabeth Ernst, Monique Grillon, Christian TI Resting State Alpha Oscillations in the Expression of Anxiety-potentiated Startle SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE anxiety potentiated startle; magnetoencephalography; alpha C1 [Balderston, Nicholas; Hale, Elizabeth; Ernst, Monique; Grillon, Christian] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 933 BP 335S EP 335S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502126 ER PT J AU Ernst, M Patel, N Grillon, C Pine, D AF Ernst, Monique Patel, Nilam Grillon, Christian Pine, Daniel TI Interaction Between Anxiety and Cognition in Adolescents and Adults SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE startle; load; workingmemory; fear; threat C1 [Ernst, Monique; Patel, Nilam; Grillon, Christian; Pine, Daniel] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 934 BP 335S EP 335S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502127 ER PT J AU Murray, SK Wei, SM Nash, TA Nguyen, TV Reding, KM Martinez, PE Boyle, DE Reuter, JM Raab, HA Brady, SM Nieman, LK Soldin, SJ Zink, CF Kippenhan, JS Kohn, PD Yanovski, JA Schmidt, PJ Berman, KF AF Murray, Shanna K. Wei, Shau-Ming Nash, Tiffany A. Tuong-Vi Nguyen Reding, Katherine M. Martinez, Pedro E. Boyle, D. Ellen Reuter, John M. Raab, Hillary A. Brady, Sheila M. Nieman, Lynnette K. Soldin, Steven J. Zink, Caroline F. Kippenhan, J. Shane Kohn, Philip D. Yanovski, Jack A. Schmidt, Peter J. Berman, Karen F. TI Differential Recruitment of and Relationship between Ventral Striatum and Prefrontal Cortex during Reward Outcome Processing in Children and Adolescents SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Adolescence; Reward; Ventral Striatum; Prefrontal Cortex; Development C1 [Murray, Shanna K.; Wei, Shau-Ming; Nash, Tiffany A.; Tuong-Vi Nguyen; Reding, Katherine M.; Raab, Hillary A.; Kippenhan, J. Shane; Kohn, Philip D.; Berman, Karen F.] NIMH, Sect Integrat Neuroimaging, Clin & Translat Neurosci Branch, Bethesda, MD 20892 USA. [Martinez, Pedro E.; Reuter, John M.; Schmidt, Peter J.] NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. [Boyle, D. Ellen; Soldin, Steven J.] NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Brady, Sheila M.; Nieman, Lynnette K.; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Bethesda, MD USA. [Zink, Caroline F.] Lieber Inst Brain Dev, Clin Sci Div, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 960 BP 345S EP 345S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502153 ER PT J AU Satterthwaite, TD Shanmugan, S Wolf, DH Calkins, ME Moore, TM Hopson, R Ruparel, K Roalf, DR Jackson, C Gennatas, ED Leibenluft, E Pine, DS Gur, RC Gur, RE AF Satterthwaite, Theodore D. Shanmugan, Sheila Wolf, Daniel H. Calkins, Monica E. Moore, Tyler M. Hopson, Ryan Ruparel, Kosha Roalf, David R. Jackson, Chad Gennatas, Efstathios D. Leibenluft, Ellen Pine, Daniel S. Gur, Ruben C. Gur, Raquel E. TI Common and Dissociable Mechanisms of Executive System Dysfunction Across Psychiatric Disorders in Youth SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE working memory; adolescence; fMRI; executive C1 [Satterthwaite, Theodore D.; Shanmugan, Sheila; Wolf, Daniel H.; Calkins, Monica E.; Moore, Tyler M.; Hopson, Ryan; Ruparel, Kosha; Roalf, David R.; Jackson, Chad; Gennatas, Efstathios D.; Gur, Ruben C.; Gur, Raquel E.] UPenn, Psychiat, Philadelphia, PA USA. [Leibenluft, Ellen; Pine, Daniel S.] NIMH, Emot & Dev Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 964 BP 347S EP 347S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502157 ER PT J AU Hantsoo, L Golden, C Appleby, D Grillon, C Epperson, CN AF Hantsoo, Liisa Golden, Carla Appleby, Dina Grillon, Christian Epperson, C. Neill TI Anxiety-Potentiated Acoustic Startle Response Is Elevated in the Luteal Phase in Women with Premenstrual Dysphoric Disorder (PMDD) Compared to Controls SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE premenstrual; PMS; acoustic startle; psychophysiology; allopregnanolone C1 [Hantsoo, Liisa; Golden, Carla; Appleby, Dina; Epperson, C. Neill] Univ Penn, Psychiat, Philadelphia, PA 19104 USA. [Grillon, Christian] NIH, Sect Neurobiol Fear & Anxiety, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1017 BP 368S EP 368S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502210 ER PT J AU Deligiannidis, KM Kroll-Desrosiers, AR Mo, S Nguyen, HP Svenson, A Jaitly, N Hall, JE Barton, BA Rothschild, AJ Shaffer, SA AF Deligiannidis, Kristina M. Kroll-Desrosiers, Aimee R. Mo, Shunyan Nguyen, Hien P. Svenson, Abby Jaitly, Nina Hall, Janet E. Barton, Bruce A. Rothschild, Anthony J. Shaffer, Scott A. TI Plasma Neuroactive Steroid and GABA Concentrations in Peripartum Women At-risk for Postpartum Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE neuroactive steroid; gamma-aminobutryic acid; postpartum; depression; peripartum C1 [Deligiannidis, Kristina M.; Svenson, Abby; Jaitly, Nina; Rothschild, Anthony J.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Kroll-Desrosiers, Aimee R.; Barton, Bruce A.] Univ Massachusetts, Sch Med, Quantitat Hlth Sci, Worcester, MA USA. [Mo, Shunyan; Nguyen, Hien P.; Shaffer, Scott A.] Univ Massachusetts, Sch Med, Proteom & Mass Spectrometry Facil, Worcester, MA USA. [Mo, Shunyan; Nguyen, Hien P.; Shaffer, Scott A.] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA USA. [Jaitly, Nina; Hall, Janet E.] NIEHS, NIH, Res Triangle Pk, NC USA. [Hall, Janet E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA USA. RI Deligiannidis, Kristina/C-3654-2014 OI Deligiannidis, Kristina/0000-0001-7439-2236 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1018 BP 369S EP 369S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502211 ER PT J AU Schiller, CE Belger, A Bizzell, J Johnson, SL Schmidt, P Rubinow, D AF Schiller, Crystal E. Belger, Aysenil Bizzell, Joshua Johnson, Sarah L. Schmidt, Peter Rubinow, David TI Effects of Gonadal Steroids on Mood and Emotion Processing in Women with a History of Postpartum Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Estrogen; Progesterone; Postpartum Depression; Women; Neuroimaging C1 [Schiller, Crystal E.; Belger, Aysenil; Bizzell, Joshua; Johnson, Sarah L.; Rubinow, David] Univ N Carolina, Psychiat, Chapel Hill, NC USA. [Schmidt, Peter] NIMH, Sect Behav Endocrinol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1020 BP 369S EP 370S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502213 ER PT J AU Simon, TJ Antshel, KM Stoddard, J Fremont, W Kates, WR AF Simon, Tony J. Antshel, Kevin M. Stoddard, Joel Fremont, Wanda Kates, Wendy R. TI A Potentially Efficient Screening Tool for Psychotic Thinking in Youth with Chromosome 22q11.2 Deletion Syndrome SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Schizophrenia; Psychosis-Proneness; Screening; 22q11.2 deletion syndrome; Prodrome C1 [Simon, Tony J.] Univ Calif Davis, Psychiat & Behav Sci, Sacramento, CA 95817 USA. [Antshel, Kevin M.] Syracuse Univ, Psychol, Syracuse, NY USA. [Stoddard, Joel] NIMH, NIH, Bethesday, MD USA. [Fremont, Wanda; Kates, Wendy R.] Syracuse Univ, Psychiat, Syracuse, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1035 BP 376S EP 376S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502228 ER PT J AU Hoffmann, MS Stringaris, A Leibenluft, E Laporte, PP Pan, PM Gadelha, A Miguel, EC Manfro, GG Rohde, LA Salum, GA AF Hoffmann, Mauricio S. Stringaris, Argyris Leibenluft, Ellen Laporte, Paola P. Pan, Pedro M. Gadelha, Ary Miguel, Euripedes C. Manfro, Gisele G. Rohde, Luis A. Salum, Giovanni A. TI The Validity of Positive Attributes Construct and its Interactions with Cognition and Psychopathology: A Developmental Economics Approach SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Noncognitive skills; Cognitive skills; Mental health; School; Friendship C1 [Hoffmann, Mauricio S.; Laporte, Paola P.] Hosp Clin Porto Alegre, Psychiat, Porto Alegre, RS, Brazil. [Stringaris, Argyris] Inst Psychiat, Dept Child & Adolescent Psychiat, London, England. [Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Bethesda, MD 20892 USA. [Pan, Pedro M.; Gadelha, Ary] Univ Fed Sao Paulo, Psychiat, Sao Paulo, Brazil. [Miguel, Euripedes C.] Univ Sao Paulo, Inst Psychiat, Sao Paulo, Brazil. [Manfro, Gisele G.; Rohde, Luis A.; Salum, Giovanni A.] Univ Fed Rio Grande do Sul, Psychiat, Porto Alegre, RS, Brazil. RI Salum, Giovanni/A-7849-2010; Pan, Pedro/I-5167-2013 OI Salum, Giovanni/0000-0002-7537-7289; Pan, Pedro/0000-0002-1943-6520 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1039 BP 377S EP 377S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502232 ER PT J AU Swedo, SE AF Swedo, Susan E. TI Treatment of PANDAS/PANS with Therapeutic Plasma Apheresis (TPA), Intravenous Immunoglobulin (IVIG) and other Immunomodulatory Therapies SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE PANDAS; PANS; Obsessive Compulsive Disorder (OCD); Intravenous immunoglobulin (IVIG); Therapeutic plasma apheresis (TPA) C1 [Swedo, Susan E.] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1041 BP 378S EP 378S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502234 ER PT J AU Hyusyan, AA Zhang, FY Adams, S Khoyetsyan, AG Straub, R Avagyan, S Jordan, F Mayilyan, KR Weinberger, DR AF Hyusyan, Armenuhi A. Zhang, Fengyu Adams, Sharon Khoyetsyan, Aren G. Straub, Richard Avagyan, Sevak Jordan, Frieda Mayilyan, Karine R. Weinberger, Daniel R. TI Multiallelic Association of the HLA-C Locus with Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE MHC; HLA class I; HLA class II; HLA imputation; FBAT C1 [Hyusyan, Armenuhi A.; Khoyetsyan, Aren G.; Mayilyan, Karine R.] Armenian NAS, Inst Mol Biol, Yerevan, Armenia. [Hyusyan, Armenuhi A.; Avagyan, Sevak; Jordan, Frieda] Armenian Bone Marrow Donor Registry Charitable Tr, Yerevan, Armenia. [Zhang, Fengyu; Straub, Richard; Mayilyan, Karine R.; Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD USA. [Adams, Sharon] NIH, HLA Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1099 BP 402S EP 402S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502292 ER PT J AU Dutta, N Helton, S Hall, S Schwandt, M Lohoff, FW AF Dutta, Nisha Helton, Sarah Hall, Sam Schwandt, Melanie Lohoff, Falk W. TI The Functional VMAT1 Variant Thr136Ile Moderates Alcohol Withdrawal Severity SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE alcohol withdrawal; VMAT1 C1 [Dutta, Nisha; Helton, Sarah; Hall, Sam; Schwandt, Melanie; Lohoff, Falk W.] NIAAA, NIH, Lab Clin Genom & Expt Therapeut, Bethesda, MD USA. RI Lohoff, Falk/M-7951-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1116 BP 409S EP 409S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502309 ER PT J AU Helton, S Dutta, N Hall, S Schwandt, M Lohoff, FW AF Helton, Sarah Dutta, Nisha Hall, Sam Schwandt, Melanie Lohoff, Falk W. TI Association Analysis between Genetic Variation in the GATA4 Gene and Alcohol Dependence SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE GATA4; alcohol dependence; gene variants; case-control C1 [Helton, Sarah; Dutta, Nisha; Hall, Sam; Schwandt, Melanie; Lohoff, Falk W.] NIAAA, NIH, Bethesda, MD USA. RI Lohoff, Falk/M-7951-2016 NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1117 BP 409S EP 409S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502310 ER PT J AU Huang, MC Schwandt, ML Heilig, M AF Huang, Ming-Chyi Schwandt, Melanie L. Heilig, Markus TI Association of FKBP5 Genetic Variants with Benzodiazepine Use in Patients Receiving Alcohol Withdrawal Treatment SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE FKBP5; Alcohol Withdrawal; Benzodiazepine; Genetic Association C1 [Huang, Ming-Chyi] Taipei City Hosp, Psychiat, Taipei City Psychiat Ctr, Taipei, Taiwan. [Schwandt, Melanie L.; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1118 BP 409S EP 409S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502311 ER PT J AU Kramer, R Mistry, M Fromer, M Elkahloun, A Lipska, BK AF Kramer, Robin Mistry, Meeta Fromer, Menachem Elkahloun, Abdel Lipska, Barbara K. TI Whole Genome Expression Patterns in Dorsolateral Prefrontal Cortex and Hippocampus in Schizophrenia, Bipolar Disorder and Major Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Schizophrenia; Bipolar; MDD; DLPFC; Hippocampus C1 [Kramer, Robin; Lipska, Barbara K.] NIMH, Human Brain Collect Core, Bethesda, MD 20892 USA. [Mistry, Meeta] Harvard Univ, Sch Publ Hlth, HSPH Bioinformat Core, Boston, MA 02115 USA. [Fromer, Menachem] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Elkahloun, Abdel] NHGRI, Microarray Core, Bethesda, MD 20892 USA. RI Lipska, Barbara/E-4569-2017 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1137 BP 416S EP 416S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502329 ER PT J AU Lipska, BK Kunii, Y Zhang, WY Xu, Q Feng, NP Wang, KH AF Lipska, Barbara K. Kunii, Yasuto Zhang, Wenyu Xu, Qing Feng, Ningping Wang, Kuan Hong TI Co-Localization of CHRNA7 and CHRFAM7A mRNA and Their Altered Expression in the Postmortem Dorsolateral Prefrontal Cortex of Patients with Major Psychiatric Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE schizophrenia; nicotinic receptor; bipolar disorder; prefrontal cortex; major depression C1 [Lipska, Barbara K.; Kunii, Yasuto; Xu, Qing; Feng, Ningping] NIMH, HBCC, Bethesda, MD 20892 USA. [Zhang, Wenyu; Wang, Kuan Hong] NIMH, DIRP, Bethesda, MD 20892 USA. RI Lipska, Barbara/E-4569-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1138 BP 416S EP 417S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502330 ER PT J AU Zhang, L Raheja, UK Shuldiner, AR Amritwar, A Sleemi, A Stiller, JW Evans, DS Hsueh, WC Snitker, S Mitchell, BD Postolache, TT AF Zhang, Layan Raheja, Uttam K. Shuldiner, Alan R. Amritwar, Ameya Sleemi, Aamar Stiller, John W. Evans, Daniel S. Hsueh, Wen-Chi Snitker, Soren Mitchell, Braxton D. Postolache, Teodor T. TI Chronotype Is Associated with Seasonal Weight and Sleep Duration Changes in the Old Order Amish SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Seasonal Pattern Assessment Questionnaire (SPAQ); Seasonal Sleep Duration Changes; Seasonal Weight Changes; Morningness-Eveningness Questionnaire (MEQ); Amish C1 [Zhang, Layan; Raheja, Uttam K.; Amritwar, Ameya; Sleemi, Aamar; Stiller, John W.] St Elizabeth Hosp, Dept Psychiat, Washington, DC USA. [Zhang, Layan; Raheja, Uttam K.; Amritwar, Ameya; Sleemi, Aamar; Postolache, Teodor T.] Univ Maryland, Sch Med, Mood & Anxiety Program, Baltimore, MD USA. [Shuldiner, Alan R.; Snitker, Soren; Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Evans, Daniel S.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Hsueh, Wen-Chi] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. [Postolache, Teodor T.] Mental Illness Res Educ & Clin Ctr MIRECC, Capitol Hlth Care Network, Baltimore, MD USA. Mental Illness Res Educ & Clin Ctr MIRECC, Capitol Hlth Care Network, Denver, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1150 BP 421S EP 422S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502342 ER PT J AU Bartholomew, ME Ihne, JL Berman, KF Weinberger, DR Callicott, JH AF Bartholomew, Morgan E. Ihne, Jessica L. Berman, Karen F. Weinberger, Daniel R. Callicott, Joseph H. TI Gene-environment Interaction Between COMT Genotype and Childhood Urbanicity on Prefrontal Efficiency in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Schizophrenia; Urbanicity; COMT C1 [Bartholomew, Morgan E.; Ihne, Jessica L.; Berman, Karen F.; Callicott, Joseph H.] NIH, Clin & Translat Neurosci Branch, Bethesda, MD 20892 USA. [Weinberger, Daniel R.] Lieber Inst Brain Dev, Clin Sci, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 572 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501166 ER PT J AU Cadet, JL AF Cadet, Jean Lud TI Transcriptional and Epigenetic Substrates of Methamphetamine Self-administration SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Methamphetamine Addiction; gene networks; epigenetics; transcription factors; self-administration C1 [Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, NIH, DHHS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 440 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501042 ER PT J AU Callicott, JH Dickinson, D Berman, KF Weinberger, DR AF Callicott, Joseph H. Dickinson, Dwight Berman, Karen F. Weinberger, Daniel R. TI General Intelligence and Associated fMRI Networks in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE intelligence; prefrontal; schizophrenia; fMRI; working memory C1 [Callicott, Joseph H.; Dickinson, Dwight; Berman, Karen F.] NIMH, Clin & Translat Neurosci Branch, NIH, Bethesda, MD 20892 USA. [Weinberger, Daniel R.] Lieber Inst Bran Dev, Clin Sci, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 574 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501168 ER PT J AU Davis, A Torrisi, S Reynolds, R O'Connell, K Balderston, N Grillon, C Ernst, M AF Davis, Andrew Torrisi, Salvatore Reynolds, Rick O'Connell, Katherine Balderston, Nicholas Grillon, Christian Ernst, Monique TI Functional Connectivity of the Human Bed Nucleus of the Stria Terminalis at Ultra High Field fMRI SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE BNST; Anxiety; fMRI; Connectivity; Subcortical C1 [Davis, Andrew; Torrisi, Salvatore; O'Connell, Katherine; Balderston, Nicholas; Grillon, Christian; Ernst, Monique] NIMH, Div Intramural Res Programs, Bethesda, MD 20892 USA. [Reynolds, Rick] NIMH, Sci & Stat Comp Core, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 631 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501225 ER PT J AU Dickinson, D Giangrande, E Pratt, D Weinberger, DR Berman, KF AF Dickinson, Dwight Giangrande, Evan Pratt, Danielle Weinberger, Daniel R. Berman, Karen F. TI Cognitive Subgrouping in People with Schizophrenia and Their Siblings: A Focus on "Neuropsychologically Normal" Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Schizophrenia; Cognition; Cluster Analysis; Subgrouping; Unaffected Siblings C1 [Dickinson, Dwight; Giangrande, Evan; Pratt, Danielle; Berman, Karen F.] NIMH, Clin & Translat Neurosci Branch, Bethesda, MD 20892 USA. [Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 573 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501167 ER PT J AU Diehl, C Cho, YST Yang, G Repovs, G Murray, JD Pearlson, GD Glahn, DC Anticevic, A AF Diehl, Caroline Cho, Youngsun T. Yang, Genevieve Repovs, Grega Murray, John D. Pearlson, Godfrey D. Glahn, David C. Anticevic, Alan TI Characterizing Striatal Connectivity Disturbances in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE schizophrenia; connectivity; striatum C1 [Diehl, Caroline; Cho, Youngsun T.; Yang, Genevieve; Pearlson, Godfrey D.; Glahn, David C.; Anticevic, Alan] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Diehl, Caroline; Anticevic, Alan] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Yang, Genevieve; Anticevic, Alan] Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, New Haven, CT USA. [Yang, Genevieve; Anticevic, Alan] Yale Univ, Interdept Neurosci Program, New Haven, CT USA. [Repovs, Grega] Univ Ljubljana, Dept Psychol, Ljubljana, Slovenia. [Murray, John D.; Pearlson, Godfrey D.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Murray, John D.] Yale Univ, Dept Phys, New Haven, CT USA. [Pearlson, Godfrey D.; Glahn, David C.; Anticevic, Alan] NIAAA, Ctr Translat Neurosci Alcoholism, New Haven, CT USA. [Pearlson, Godfrey D.] Hartford Hosp, Olin Neuropsychiat Res Ctr, Hartford, CT 06115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 685 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501279 ER PT J AU Farokhnia, M Haass-Koffler, C Zywiak, W Swift, RM Kenna, GA Leggio, L AF Farokhnia, Mehdi Haass-Koffler, Carolina Zywiak, William Swift, Robert M. Kenna, George A. Leggio, Lorenzo TI Noradrenergic System as a Pharmacological Target for Alcoholism: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept, Clinical Trial with Doxazosin SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Doxazosin; Noradrenergic System; Alcohol Dependence; Alcohol Use Disorder; Clinical Trial C1 [Farokhnia, Mehdi; Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Farokhnia, Mehdi; Leggio, Lorenzo] NIDA, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Haass-Koffler, Carolina; Zywiak, William; Swift, Robert M.; Kenna, George A.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. RI Leggio, Lorenzo/M-2972-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 500 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501094 ER PT J AU Grannan, MD Bubser, M Bridges, TM Gould, RW Dencker, D Daniels, JS Noetzel, MJ Niswender, CM Duggan, ME Brandon, NJ Dunlop, J Wood, MW Wess, J Wood, MR Lindsley, CW Conn, PJ Jones, CK AF Grannan, Michael D. Bubser, Michael Bridges, Thomas M. Gould, Robert W. Dencker, Ditte Daniels, J. Scott Noetzel, Meredith J. Niswender, Colleen M. Duggan, Mark E. Brandon, Nicholas J. Dunlop, John Wood, Michael W. Wess, Jurgen Wood, Michael R. Lindsley, Craig W. Conn, P. Jeffrey Jones, Carrie K. TI Effects of the M4 Positive Allosteric Modulator VU0467154 on Cognition and Electrophysiological Properties in the mPFC SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Schizophrenia; Cognition; PAM; electrophysiology C1 [Grannan, Michael D.; Bubser, Michael; Bridges, Thomas M.; Gould, Robert W.; Daniels, J. Scott; Noetzel, Meredith J.; Niswender, Colleen M.; Wood, Michael R.; Lindsley, Craig W.; Conn, P. Jeffrey; Jones, Carrie K.] Vanderbilt Univ, Pharmacol, Nashville, TN 37235 USA. [Grannan, Michael D.; Bubser, Michael; Bridges, Thomas M.; Gould, Robert W.; Daniels, J. Scott; Noetzel, Meredith J.; Niswender, Colleen M.; Wood, Michael R.; Lindsley, Craig W.; Conn, P. Jeffrey; Jones, Carrie K.] Vanderbilt Univ, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37235 USA. [Dencker, Ditte] Copenhagen Univ Hosp, Lab Neuropsychiat, Copenhagen, Denmark. [Duggan, Mark E.; Brandon, Nicholas J.; Dunlop, John; Wood, Michael W.] AstraZeneca, Neurosci Innovat Med, Cambridge, MA USA. [Wess, Jurgen] NIH, Lab Bioorgan Chem, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 740 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501333 ER PT J AU Holmes, A AF Holmes, Andrew TI Amygdala Circuit Mechanisms Moderating Pharmacological Rescue of Fear Extinction Impairments SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE cannabinoid; fluoxetine; amygdala; fear; plasticity C1 [Holmes, Andrew] NIAAA, LBGN, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 6 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 416 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501018 ER PT J AU Hsu, DT Mickey, BJ Langenecker, SA Heitzeg, MM Love, TM Wang, H Kennedy, SE Pecina, M Shafir, T Hodgkinson, CA Enoch, MA Goldman, D Zubieta, JK AF Hsu, David T. Mickey, Brian J. Langenecker, Scott A. Heitzeg, Mary M. Love, Tiffany M. Wang, Heng Kennedy, Susan E. Pecina, Marta Shafir, Tal Hodgkinson, Colin A. Enoch, Mary-Anne Goldman, David Zubieta, Jon-Kar TI Allelic Variation in the Corticotropin-Releasing Hormone Receptor 1 (CRHR1) Gene Influences fMRI Signal Responses to Emotional Stimuli SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE corticotropin-releasing; CRH; stress; fMRI; CRHR1 C1 [Hsu, David T.] SUNY Stony Brook, Psychiat, Stony Brook, NY 11794 USA. [Mickey, Brian J.; Heitzeg, Mary M.; Love, Tiffany M.; Wang, Heng; Pecina, Marta; Zubieta, Jon-Kar] Univ Michigan, Psychiat, Ann Arbor, MI 48109 USA. [Langenecker, Scott A.] Univ Illinois, Psychiat, Chicago, IL USA. [Kennedy, Susan E.] Univ Alabama, Biol Sci, Tuscaloosa, AL USA. [Shafir, Tal] Univ Haifa, Social Welf & Hlth Sci, IL-31999 Haifa, Israel. [Hodgkinson, Colin A.; Enoch, Mary-Anne; Goldman, David] NIAAA, Neurogenet Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 434 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501036 ER PT J AU Koob, GF AF Koob, George F. TI Addiction as a Stress Surfeit Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat ID ANTAGONISM; HEROIN; RATS C1 [Koob, George F.] NIAAA, NIH, Washington, DC USA. RI koob, george/P-8791-2016 NR 5 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 401 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501003 ER PT J AU Krasnova, IN AF Krasnova, Irina N. TI Molecular Mechanisms Underlying Incubation of Methamphetamine Craving SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE methamphetamine; self-administration; punishment; craving; histone diacetylase C1 [Krasnova, Irina N.] NIDA, Mol Neuropsychiat Res Branch, NIH, DHHS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 441 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501043 ER PT J AU Kwako, LE Warmingham, JM Goldman, D George, DT Heilig, M Ramchandani, VA Schwandt, ML AF Kwako, Laura E. Warmingham, Jennifer M. Goldman, David George, David T. Heilig, Markus Ramchandani, Vijay A. Schwandt, Melanie L. TI Early Life Stress and Suicide in Treatment-Seeking Alcoholics SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Alcoholism; Suicide; Posttraumatic stress disorder; Trauma; Addiction C1 [Kwako, Laura E.; Goldman, David; George, David T.] NIAAA, Off Clin Director, NIH, Bethesda, MD USA. [Warmingham, Jennifer M.; Heilig, Markus; Ramchandani, Vijay A.; Schwandt, Melanie L.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 604 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501198 ER PT J AU Luscher, ZI Ordonez, AE Sastry, NV Watsky, RE Greenstein, D Clasen, L Rapoport, J Gogtay, N AF Luscher, Zoe I. Ordonez, Anna E. Sastry, Nevin V. Watsky, Rebecca E. Greenstein, Deanna Clasen, Liv Rapoport, Judith Gogtay, Nitin TI Structural Magnetic Resonance Imaging of the Amygdala in Patients with Childhood-Onset Schizophrenia, their Non-Psychotic Siblings, and Healthy Volunteers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Schizophrenia; amygdala; childhood; siblings; MRI C1 [Luscher, Zoe I.; Ordonez, Anna E.; Sastry, Nevin V.; Watsky, Rebecca E.; Greenstein, Deanna; Clasen, Liv; Rapoport, Judith; Gogtay, Nitin] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 674 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501268 ER PT J AU McMahon, FJ AF McMahon, Francis J. CA Consortium Lithium Genetics TI Genomewide Association Study Implicates a Long Noncoding (lnc) RNA in the Response to Lithium for Bipolar Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE pharmacogenomics; bipolar; mood stabilizers C1 [McMahon, Francis J.; Consortium Lithium Genetics] NIMH, Human Genet Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 612 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501206 ER PT J AU Pine, DS AF Pine, Daniel S. TI Shared and Specific Neural Correlates of Pediatric Anxiety Phenotypes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE anxiety; fMRI C1 [Pine, Daniel S.] NIMH, IRP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 405 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501007 ER PT J AU Richards, EM Zanotti-Fregonara, P Fujita, M Walls, T Niciu, MJ Machado-Vieira, R Salvadore, G Kolb, H Zarate, CA Innis, RB AF Richards, Erica M. Zanotti-Fregonara, Paolo Fujita, Masahiro Walls, Tessa Niciu, Mark J. Machado-Vieira, Rodrigo Salvadore, Giacomo Kolb, Hartmuth Zarate, Carlos A. Innis, Robert B. TI Increased PET Radioligand Binding to Translocator Protein Suggests that Major Depressive Disorder Is Associated with Neuroinflammation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE PET; Inflammation; TSPO; Depression C1 [Richards, Erica M.; Walls, Tessa; Niciu, Mark J.; Machado-Vieira, Rodrigo; Zarate, Carlos A.] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Zanotti-Fregonara, Paolo; Fujita, Masahiro; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Salvadore, Giacomo] Janssen Res & Dev LLC, Neurosci Expt Med, Titusville, NJ USA. [Kolb, Hartmuth] Janssen Res & Dev LLC, Neurosci Biomakers, San Diego, CA USA. RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 652 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501246 ER PT J AU Schuebel, KE AF Schuebel, Kornel E. TI Epigenomic Responses to Alcohol in a Rat Model of Fetal Alcohol Spectrum Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Epigenetics; Fetal alcohol spectrum disorders; Alcohol; Choline; Gene expression C1 [Schuebel, Kornel E.] NIAAA, Neurogenet Lab, NIH, DHHS, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 443 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501045 ER PT J AU Stangl, BL Hendershot, CS Ramchandani, VA AF Stangl, Bethany L. Hendershot, Christian S. Ramchandani, Vijay A. TI Determinants of Intravenous Self-administration of Alcohol in Humans: Impulsivity and Attention SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE IV Alcohol; Self-administration; Impulsivity; Attention; Social Drinkers C1 [Stangl, Bethany L.; Ramchandani, Vijay A.] NIAAA, NIH, Sect Human Psychopharmacol, Bethesda, MD USA. [Hendershot, Christian S.] Campbell Family Mental Hlth Res Inst, Ctr Addict & Mental Hlth, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 504 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501098 ER PT J AU Steuber, ER Gold, AL Pacheco, J Leibenluft, E Pine, DS AF Steuber, Elizabeth R. Gold, Andrea L. Pacheco, Jennifer Leibenluft, Ellen Pine, Daniel S. TI Brain Morphometry in Pediatric Anxiety Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Anxiety Disorders; Pediatrics; Freesurfer; Cortical Thickness; Gray Matter Volume C1 [Steuber, Elizabeth R.; Gold, Andrea L.; Leibenluft, Ellen; Pine, Daniel S.] NIMH, Emot & Dev Branch, Bethesda, MD 20892 USA. [Pacheco, Jennifer] Natl Intrepid Ctr Excellence, Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 632 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501226 ER PT J AU Tromp, DPM Williams, LE Fox, AS Oler, JA Rogers, GR Pine, DS Kalin, NH AF Tromp, Do P. M. Williams, Lisa E. Fox, Andrew S. Oler, Jonathan A. Rogers, Gregory R. Pine, Daniel S. Kalin, Ned H. TI White Matter Alterations in Pre-Adolescent Children with Anxiety Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Anxiety Disorders; Pre-adolescents; Diffusion Tensor Imaging; White Matter C1 [Tromp, Do P. M.; Williams, Lisa E.; Fox, Andrew S.; Oler, Jonathan A.; Rogers, Gregory R.; Kalin, Ned H.] Univ Wisconsin, Psychiat, Madison, WI USA. [Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 642 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501236 ER PT J AU Tseng, WL Tseng, MB Deveney, C Machlin, L Moroney, E Towbin, K Pine, D Leibenluft, E AF Tseng, Wan-Ling Tseng, Melissa Brotman Deveney, Christen Machlin, Laura Moroney, Elizabeth Towbin, Kenneth Pine, Daniel Leibenluft, Ellen TI Neural Correlates of Irritability across Diagnoses: Categorical and Dimensional Approaches SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE irritability; DMDD; fMRI; categorical; dimensional C1 [Tseng, Wan-Ling; Tseng, Melissa Brotman; Machlin, Laura; Moroney, Elizabeth; Towbin, Kenneth; Pine, Daniel; Leibenluft, Ellen] NIMH, Emot & Dev Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Deveney, Christen] Wellesley Coll, Dept Psychol, Wellesley, MA 02181 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 653 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501247 ER PT J AU Warner, V Xu, DR Liu, J Xao, XJ Jiang, YW Durken, K Grillon, C AF Warner, Virginia Xu, Dongrong Liu, Jun Xao, Xuejun Jiang, Yuwei Durken, Kathleen Grillon, Christian TI White Matter Integrity and Its Association with Overactive Defense Survival Circuitry: Three Generation Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE startle; diffusion imaging; depression; 3 generations C1 [Warner, Virginia; Xu, Dongrong; Liu, Jun; Xao, Xuejun; Jiang, Yuwei] New York State Psychiat Inst & Hosp, Epidemiol, New York, NY 10032 USA. [Durken, Kathleen] New York State Psychiat Inst & Hosp, MRI Unit, New York, NY 10032 USA. [Grillon, Christian] NIMH, Neurobiol Fear & Anxiety, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 743 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501336 ER PT J AU Watsky, RE Gotts, SJ Berman, RA Sastry, NV Luscher, ZI McAdams, HM Greenstein, D Lalonde, F Martin, A Ordonez, AE Gogtay, N Rapoport, JL AF Watsky, Rebecca E. Gotts, Stephen J. Berman, Rebecca A. Sastry, Nevin V. Luscher, Zoe I. McAdams, Harrison M. Greenstein, Dede Lalonde, Francois Martin, Alex Ordonez, Anna E. Gogtay, Nitin Rapoport, Judith L. TI Resting State Networks in the Non-Psychotic Siblings of Patients with Childhood-Onset Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Schizophrenia; Neuroimaging; Functional MRI; Childhood psychosis C1 [Watsky, Rebecca E.; Berman, Rebecca A.; Sastry, Nevin V.; Luscher, Zoe I.; McAdams, Harrison M.; Greenstein, Dede; Lalonde, Francois; Ordonez, Anna E.; Gogtay, Nitin; Rapoport, Judith L.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Gotts, Stephen J.; Martin, Alex] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 672 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501266 ER PT J AU Williams, LE Oler, JA Fox, AS McFarlin, DR Rogers, GM Jesson, MAL Davidson, RJ Pine, DS Kalin, NH AF Williams, Lisa E. Oler, Jonathan A. Fox, Andrew S. McFarlin, Daniel R. Rogers, Gregory M. Jesson, Maria A. L. Davidson, Richard J. Pine, Daniel S. Kalin, Ned H. TI Fear of the Unknown: Increased Neural Activation During Uncertain Anticipation in Childhood Anxiety Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE anxiety disorders; childhood; amygdala; uncertainty; anticipation C1 [Williams, Lisa E.; Oler, Jonathan A.; Fox, Andrew S.; McFarlin, Daniel R.; Rogers, Gregory M.; Jesson, Maria A. L.; Kalin, Ned H.] Univ Wisconsin, Psychiat, Madison, WI USA. [Davidson, Richard J.] Univ Wisconsin, Psychol, Madison, WI USA. [Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 643 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501237 ER PT J AU Sakloth, F Kolanos, R Mosier, PD Bonano, JS Banks, ML Partilla, JS Baumann, MH Negus, SS Glennon, RA AF Sakloth, F. Kolanos, R. Mosier, P. D. Bonano, J. S. Banks, M. L. Partilla, J. S. Baumann, M. H. Negus, S. S. Glennon, R. A. TI Steric parameters, molecular modeling and hydropathic interaction analysis of the pharmacology of para-substituted methcathinone analogues SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article ID HUMAN SEROTONIN TRANSPORTER; DOPAMINE TRANSPORTER; MONOAMINE TRANSPORTERS; SUBSTRATE TRANSPORT; CONCISE GUIDE; BINDING-SITE; BATH SALTS; COCAINE; VALIDATION; MEPHEDRONE AB Background and PurposeThere is growing concern over the abuse of certain psychostimulant methcathinone (MCAT) analogues. This study extends an initial quantitative structure-activity relationship (QSAR) investigation that demonstrated important steric considerations of seven 4- (or para-)substituted analogues of MCAT. Specifically, the steric character (Taft's steric E-S) of the 4-position substituent affected in vitro potency to induce monoamine release via dopamine and 5-HT transporters (DAT and SERT) and in vivo modulation of intracranial self-stimulation (ICSS). Here, we have assessed the effects of other steric properties of the 4-position substituents. Experimental ApproachDefinitive steric parameters that more explicitly focus on the volume, width and length of the MCAT 4-position substituents were assessed. In addition, homology models of human DAT and human SERT based upon the crystallized DrosophilaDAT were constructed and docking studies were performed, followed by hydropathic interaction (HINT) analysis of the docking results. Key ResultsThe potency of seven MCAT analogues at DAT was negatively correlated with the volume and maximal width of their 4-position substituents, whereas potency at SERT increased as substituent volume and length increased. SERT/DAT selectivity, as well as abuse-related drug effects in the ICSS procedure, also correlated with the same parameters. Docking solutions offered a means of visualizing these findings. Conclusions and ImplicationsThese results suggest that steric aspects of the 4-position substituents of MCAT analogues are key determinants of their action and selectivity, and that the hydrophobic nature of these substituents is involved in their potency at SERT. C1 [Sakloth, F.; Kolanos, R.; Mosier, P. D.; Glennon, R. A.] Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, Richmond, VA 23298 USA. [Bonano, J. S.; Banks, M. L.; Negus, S. S.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. [Partilla, J. S.; Baumann, M. H.] NIDA, Designer Drug Res Unit, Intramural Res Program, NIH, Baltimore, MD USA. RP Glennon, RA (reprint author), Virginia Commonwealth Univ, Box 980540, Richmond, VA 23298 USA. EM glennon@vcu.edu RI Banks, Matthew/K-4429-2014 OI Banks, Matthew/0000-0003-4949-5246 FU National Institutes of Health [R01DA033930] FX This research was supported by National Institutes of Health (Grant No. R01DA033930). NR 36 TC 6 Z9 6 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1188 EI 1476-5381 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAY PY 2015 VL 172 IS 9 BP 2210 EP 2218 DI 10.1111/bph.13043 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CF8LB UT WOS:000352809900003 PM 25522019 ER PT J AU Graham, BS Ambrosino, DM AF Graham, Barney S. Ambrosino, Donna M. TI History of passive antibody administration for prevention and treatment of infectious diseases SO CURRENT OPINION IN HIV AND AIDS LA English DT Review DE antibody; history; immunoglobulin; passive immunization; serum therapy ID ARGENTINE HEMORRHAGIC-FEVER; SOLUBLE SPECIFIC SUBSTANCE; B-CELLS; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; IMMUNE PLASMA; SERUM THERAPY; PNEUMOCOCCUS; VIRUS; ANTIGEN AB Purpose of review We describe the history of passive immunization to provide context for the series of articles to follow. The history of passive immunization with antibodies to prevent or treat infectious diseases is a story of different eras. There was an extraordinary era of discovery and clinical implementation before the chemical nature of antibodies was even known. This empirical process provided the resources and reagents used to describe and characterize humoral immunity, better define the chemical properties and structure of antibodies, and extend the clinical use of immunoglobulin products to treat or prevent multiple viral and bacterial diseases over the ensuing several decades. The next distinct era came with the discovery of processes to produce monoclonal antibodies (mAbs), and development of more specific therapies. Interestingly, mAb technology resulted in many products to treat autoimmune and allergic diseases, but only one common infectious disease, respiratory syncytial virus, and only in a restricted population of high-risk infants. Recent findings The current era began in 2003 with a series of publications demonstrating processes for rapidly producing human mAbs. Summary This technology combined with new sequencing technology, advances in structural biology, atomic-level molecular design, and increased capacity for synthetic biology, promises new opportunities to apply passive immunization to the prevention and treatment of infectious diseases. C1 [Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Ambrosino, Donna M.] CVC, Rockville, MD USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Bldg 40,Room 2502, Bethesda, MD 20892 USA. EM bgraham@nih.gov FU National Institute of Allergy and Infectious Diseases FX This work was supported by intramural funding from the National Institute of Allergy and Infectious Diseases. NR 29 TC 8 Z9 8 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1746-630X EI 1746-6318 J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2015 VL 10 IS 3 BP 129 EP 134 DI 10.1097/COH.0000000000000154 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CF8GG UT WOS:000352793600001 PM 25760933 ER PT J AU Dey, B Berger, EA AF Dey, Barna Berger, Edward A. TI Towards an HIV cure based on targeted killing of infected cells: different approaches against acute versus chronic infection SO CURRENT OPINION IN HIV AND AIDS LA English DT Review DE chimeric antigen receptor; Fc-mediated effector functions; genetically modified T cells; HIV cure; recombinant immunotoxins; T cell receptor; targeted cytotoxic therapy ID COMBINATION ANTIRETROVIRAL THERAPY; CD8(+) T-CELLS; IMMUNODEFICIENCY-VIRUS-INFECTION; BROADLY NEUTRALIZING ANTIBODIES; CANCER-THERAPY; IN-VIVO; RECOMBINANT IMMUNOTOXIN; LOW IMMUNOGENICITY; FOLLICULAR HELPER; GENE-THERAPY AB Purpose of review Current regimens of combination antiretroviral therapy (cART) offer effective control of HIV infection, with maintenance of immune health and near-normal life expectancy. What will it take to progress beyond the status quo, whereby infectious virus can be eradicated (a 'sterilizing cure') or fully controlled without the need for ongoing cART (a 'functional cure')? Recent findings On the basis of therapeutic advances in the cancer field, we propose that targeted cytotoxic therapy to kill HIV-infected cells represents a logical complement to cART for achieving an HIV cure. This concept is based on the fact that cART effectively blocks replication of the virus, but does not eliminate cells that are already infected; targeted cytotoxic therapy would contribute precisely this missing component. We suggest that different modalities are suited for curing primary acute versus established chronic infection. For acute infection, relatively short-acting potent agents such as recombinant immunotoxins might prove sufficient for HIV eradication, whereas for chronic infection, a long-lasting (lifelong?) modality is required to maintain full virus control, as might be achieved with genetically modified autologous T cells. Summary We present perspectives for complementing cART with targeted cytotoxic therapy, whereby HIV infection is either eradicated or fully controlled, thereby eliminating the need for lifelong cART. C1 [Dey, Barna; Berger, Edward A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Berger, EA (reprint author), NIH, 33 North Dr,Room 1E19A, Bethesda, MD 20892 USA. EM edward_berger@nih.gov FU Division of Intramural Research of NIAID; NIH Intramural AIDS Targeted Antiviral Program FX Authors were supported by the Division of Intramural Research of NIAID and by the NIH Intramural AIDS Targeted Antiviral Program. NR 68 TC 4 Z9 4 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1746-630X EI 1746-6318 J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2015 VL 10 IS 3 BP 207 EP 213 DI 10.1097/COH.0000000000000151 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CF8GG UT WOS:000352793600011 PM 25710815 ER PT J AU Kim, JW Tomita, Y Trepel, J Apolo, AB AF Kim, Joseph W. Tomita, Yusuke Trepel, Jane Apolo, Andrea B. TI Emerging immunotherapies for bladder cancer SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE adoptive T-cell therapy; B7-H3; bladder cancer; immune escape; immunotherapy; NY-ESO-1; OX40; programmed death-ligand 1; urothelial carcinoma ID RESISTANT PROSTATE-CANCER; METASTATIC UROTHELIAL CARCINOMA; PHASE-III TRIAL; NEOADJUVANT CHEMOTHERAPY; IMMUNE-RESPONSES; COSTIMULATORY MOLECULE; ANTI-PD-L1 ANTIBODY; CLINICAL ACTIVITY; CELL-CARCINOMA; T-CELLS AB Purpose of review Inhibition of immune escape mechanisms, such as the programed death-ligand 1 pathway, has demonstrated rapid, durable responses in multiple tumor types, including advanced urothelial carcinoma. This review discusses emerging immunotherapies for urothelial carcinoma in various stages of clinical development. Recent findings Urothelial carcinoma has a high mutational burden, which may increase the number of tumor antigens and potentially enhance the ability of the immune system to recognize tumor cells as foreign. However, urothelial carcinoma can evade the immune system by downregulating tumor-antigen presentation, upregulating various immune checkpoints, and inactivating cytotoxic T cells. Immunotherapies for urothelial carcinoma target each of these steps to restore immune-mediated cytotoxicity. Many of these agents are in clinical trials for urothelial carcinoma. Summary Immunotherapies are active in urothelial carcinoma, but only in a fraction of patients, implying the presence of persistent immune escape. Identifying the mechanisms of immune escape and developing rational combinatorial regimens may make the benefit of immunotherapy accessible to a broader population. C1 [Kim, Joseph W.] Yale Univ, Sch Med, Yale Canc Ctr, Prostate & Urol Canc Program, New Haven, CT USA. [Tomita, Yusuke; Trepel, Jane] NCI, NIH, Dev Therapeut Branch, Bethesda, MD 20892 USA. [Apolo, Andrea B.] NCI, NIH, Ctr Canc Res, Genitourinary Malignancies Branch, Bethesda, MD 20892 USA. RP Apolo, AB (reprint author), 10 Ctr Dr,Rm 12N226,MSC 1906, Bethesda, MD 20892 USA. EM andrea.apolo@nih.gov FU National Institutes of Health; Intramural Research Program of the Center for Cancer Research, National Cancer Institute FX The authors from National Institutes of Health are supported by funds from the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, and National Institutes of Health. NR 89 TC 8 Z9 8 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8746 EI 1531-703X J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD MAY PY 2015 VL 27 IS 3 BP 191 EP 200 DI 10.1097/CCO.0000000000000177 PG 10 WC Oncology SC Oncology GA CF6ES UT WOS:000352650300007 PM 25811346 ER PT J AU Su, D Singer, EA Srinivasan, R AF Su, Daniel Singer, Eric A. Srinivasan, Ramaprasad TI Molecular pathways in renal cell carcinoma: recent advances in genetics and molecular biology SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE molecular pathways; renal cell carcinoma; targeted therapy ID FUMARATE HYDRATASE; SIGNALING PATHWAY; CANCER-THERAPY; KIDNEY CANCER; GROWTH-FACTOR; C-MET; BAP1; NRF2; MUTATIONS; SURVIVAL AB Purpose of review Advanced renal cell carcinoma (RCC) remains a largely incurable disease with a grave prognosis despite the availability of a multiplicity of systemic therapies targeted against vascular endothelial growth factor, its receptors, and the mammalian target of rapamycin. Although immune 'checkpoint inhibitors' appear to have activity in clear cell RCC based on recent early phase trials, the true magnitude of the benefit conferred by these agents remains to be fully understood. Given the limitations of existing treatment paradigms, ongoing research into new targetable pathways is critical. This review will highlight some of the more promising avenues of investigation into the molecular biology of RCC. Recent findings The hypoxia-inducible factor and mammalian target of rapamycin pathways remain critical targets in clear cell RCC. In addition, genes involved in chromatin remodeling such as polybromo 1 (PBRM1), SET domain containing 2 (SETD2), and BRCA-1-associated protein-1 (BAP1) have been shown to influence tumor biology and predict survival. MET alterations and the Krebs cycle enzyme fumarate hydratase are associated with familial type 1 and type 2 papillary RCC (PRCC), respectively. Alterations in nuclear factor (erythroid-derived 2)-like 2, Kelch-like erythroid-derived cap-n-collar homology-associated protein 1, and cullin 3, components of an oxidative stress response pathway, have been recently recognized in some sporadic papillary tumors as well as in fumarate hydratase-deficient tumor and may serve as additional therapeutic targets. In addition, whole-genome sequencing and integrated genomic analysis strategies are beginning to uncover unique molecular signatures associated with distinct subtypes of RCC, laying the foundation for a molecular classification of RCC and more precise, mechanism-based therapeutic intervention. Summary The complex molecular changes underlying individual RCC variants are yet to be fully elucidated and remain the subject of ongoing investigation. The findings summarized here further exemplify the diversity of RCC and the need to tailor our therapeutic approaches to the unique genetic alterations specific to individual subtypes of RCC. C1 [Su, Daniel; Srinivasan, Ramaprasad] NCI, Ctr Canc Res, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Singer, Eric A.] Rutgers Canc Inst New Jersey, Sect Urol Oncol, New Brunswick, NJ USA. [Singer, Eric A.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. RP Srinivasan, R (reprint author), NCI, Ctr Canc Res, Urol Oncol Branch, Mol Canc Sect, 10 Ctr Dr,CRC2-5950, Bethesda, MD 20892 USA. EM ramasrin@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, USA; National Cancer Institute [P30CA072720] FX This research was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, USA, and by a grant from the National Cancer Institute (P30CA072720). NR 56 TC 6 Z9 8 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8746 EI 1531-703X J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD MAY PY 2015 VL 27 IS 3 BP 217 EP 223 DI 10.1097/CCO.0000000000000186 PG 7 WC Oncology SC Oncology GA CF6ES UT WOS:000352650300010 PM 25811348 ER PT J AU Bouchelouche, K Turkbey, B Choyke, PL AF Bouchelouche, Kirsten Turkbey, Baris Choyke, Peter L. TI Advances in imaging modalities in prostate cancer SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE MRI; PET/CT; PET/MRI; prostate cancer; transrectal ultrasound ID LYMPH-NODE DISSECTION; EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY; ANDROGEN-DEPRIVATION THERAPY; GA-68-LABELED PSMA LIGAND; FUSION-GUIDED BIOPSY; C-11-CHOLINE PET/CT; RADICAL PROSTATECTOMY; F-18-FLUOROCHOLINE PET/CT; BIOCHEMICAL RELAPSE; BONE-SCINTIGRAPHY AB Purpose of review Imaging plays an important role in the clinical management of prostate cancer (PCa). Thus, much effort has gone into improving imaging modalities in PCa. This review focuses on the recent advancements in transrectal ultrasound, MRI and PET during the past year. Recent findings Contrast-enhanced transrectal ultrasound with microbubbles may be useful in PCa, but needs further evaluation before more widespread use. Multiparametric MRI has emerged as a valuable tool to assist clinical management of PCa, and great progress has been made in the past year. Several radionuclides for PET/computed tomography have been tested in clinical trials; most of the studies have used radiolabeled choline. However, new PET tracers such as F-18-1-amino-3-fluorine 18-fluorocyclobutane-1-carboxylic acid and Ga-68-labeled prostate-specific membrane antigen ligands are demonstrating promising results. PET/MRI may further improve imaging in PCa, but this imaging modality needs to be evaluated further. Summary Several advances in the imaging of PCa have been made during the past year. In particular, important clinical developments have been reported in multiparametric MRI, PET/computed tomography, and PET/MRI. The continuing development of imaging techniques in PCa has the potential to optimize treatment of PCa. However, the optimal imaging strategies for each of the major clinical scenarios in PCa have not yet been identified. C1 [Bouchelouche, Kirsten] Aarhus Univ Hosp, Dept Nucl Med, DK-8200 Aarhus, Denmark. [Bouchelouche, Kirsten] Aarhus Univ Hosp, PET Ctr, DK-8200 Aarhus, Denmark. [Turkbey, Baris; Choyke, Peter L.] NCI, Ctr Canc Res, Mol Imaging Program, Bethesda, MD 20892 USA. RP Bouchelouche, K (reprint author), Aarhus Univ Hosp, Dept Nucl Med, Palle Juul Jensens Blvd 99, DK-8200 Aarhus, Denmark. EM kirsbouc@rm.dk NR 88 TC 2 Z9 2 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8746 EI 1531-703X J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD MAY PY 2015 VL 27 IS 3 BP 224 EP 231 DI 10.1097/CCO.0000000000000174 PG 8 WC Oncology SC Oncology GA CF6ES UT WOS:000352650300011 PM 25715326 ER PT J AU Hallett, M AF Hallett, M. TI The dystonias: a heterogeneous collection SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Editorial Material ID CEREBELLUM AB Click to view the accompanying paper in this issue. C1 NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov FU Intramural NIH HHS NR 4 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD MAY PY 2015 VL 22 IS 5 BP 741 EP 742 DI 10.1111/ene.12526 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CF5BC UT WOS:000352568600003 PM 25065529 ER PT J AU Khan, BA Yeh, AJ Cheung, GYC Otto, M AF Khan, Burhan A. Yeh, Anthony J. Cheung, Gordon Y. C. Otto, Michael TI Investigational therapies targeting quorum-sensing for the treatment of Staphylococcus aureus infections SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE quorum-sensing; quorum-sensing blockers; Staphylococcus aureus; Staphylococcus epidermidis ID VIRULENCE-GENE-EXPRESSION; 2-COMPONENT REGULATORY SYSTEM; BIOFILM FORMATION; PSEUDOMONAS-AERUGINOSA; AUTOINDUCING PEPTIDE; CYCLIC DIPEPTIDES; ALPHA-HEMOLYSIN; CROSS-TALK; IN-VITRO; MARINE PHOTOBACTERIUM AB Introduction: Antibiotic resistance is a serious global health concern for developed and developing nations. MRSA represents a particularly severe public health threat that is associated with high morbidity and mortality. The lack of novel antibiotics has led scientists to explore therapies targeting bacterial virulence mechanisms and virulence regulators, including those controlling cell-cell communication. Areas covered: The authors discuss the role of quorum-sensing in Staphylococcus aureus infections and components of the system that are being targeted using novel investigational drugs. In particular, the authors examine the role of the accessory gene regulator (Agr) system in virulence regulation of S. aureus pathogenesis. Finally, the authors present and compare natural and synthetic compounds that have been found to interfere with Agr functionality. Expert opinion: There is a great need to develop new therapeutic methods to combat S. aureus infections. These include anti-virulence therapies that target key global regulators involved with the establishment and propagation of infection. Several molecules have been found to interfere with S. aureus virulence regulation, especially those targeting the Agr quorum-sensing signaling molecule. These preliminary findings warrant further investigation and validation, with the goal of refining a compound that has broadspectrum inhibitory effects on most S. aureus strains and Agr subtypes. C1 [Khan, Burhan A.] NIAID, NIH, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. [Yeh, Anthony J.; Cheung, Gordon Y. C.; Otto, Michael] NIAID, NIH, Lab Human Bacterial Pathogenesis, Bethesda, MD 20892 USA. RP Otto, M (reprint author), NIAID, NIH, Lab Human Bacterial Pathogenesis, Bldg 33,1W10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), The National Institutes of Health (NIH); NIAID FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), The National Institutes of Health (NIH). BA Khan and AJ Yeh have post baccalaureate fellowships from the NIAID. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 133 TC 13 Z9 13 U1 3 U2 40 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 EI 1744-7658 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD MAY PY 2015 VL 24 IS 5 BP 689 EP 704 DI 10.1517/13543784.2015.1019062 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CF6EF UT WOS:000352648800008 PM 25704585 ER PT J AU Nikolaeva, D Draper, SJ Biswas, S AF Nikolaeva, Daria Draper, Simon J. Biswas, Sumi TI Toward the development of effective transmission-blocking vaccines for malaria SO EXPERT REVIEW OF VACCINES LA English DT Review DE genome; malaria; membrane feeding assay; Plasmodium falciparum; transmission-blocking vaccine ID PARASITE PLASMODIUM-FALCIPARUM; GAMETE-SURFACE PROTEIN; CELL-FREE SYSTEM; MOSQUITO MIDGUT INVASION; IN-VIVO ELECTROPORATION; AERUGINOSA EXOPROTEIN-A; MEMBRANE-FEEDING ASSAY; SEXUAL-STAGE ANTIGEN; ANOPHELES-GAMBIAE; RECOMBINANT PROTEINS AB The continued global burden of malaria can in part be attributed to a complex lifecycle, with both human hosts and mosquito vectors serving as transmission reservoirs. In preclinical models of vaccine-induced immunity, antibodies to parasite sexual-stage antigens, ingested in the mosquito blood meal, can inhibit parasite survival in the insect midgut as judged by ex vivo functional studies such as the membrane feeding assay. In an era of renewed political momentum for malaria elimination and eradication campaigns, such observations have fueled support for the development and implementation of so-called transmission-blocking vaccines. While leading candidates are being evaluated using a variety of promising vaccine platforms, the field is also beginning to capitalize on global '-omics' data for the rational genome-based selection and unbiased characterization of parasite and mosquito proteins to expand the candidate list. This review covers the progress and prospects of these recent developments. C1 [Nikolaeva, Daria; Draper, Simon J.; Biswas, Sumi] Univ Oxford, Jenner Inst, Oxford OX3 7DQ, England. [Nikolaeva, Daria] NIAID, Malaria Immunol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Nikolaeva, D (reprint author), Univ Oxford, Jenner Inst, Old Rd Campus Res Bldg,Roosevelt Dr, Oxford OX3 7DQ, England. EM daria.nikolaeva@ndm.ox.ac.uk OI Draper, Simon/0000-0002-9415-1357 FU Intramural Research Program of the NIAID/NIH; UK Medical Research Council Career Development Fellow [G1000527]; Jenner Investigator; Lister Institute Research Prize Fellow FX D Nikolaeva is a student of the NIH-Oxford/Cambridge Scholars Program; this publication was supported in part by the Intramural Research Program of the NIAID/NIH. SJ Draper is a UK Medical Research Council Career Development Fellow (Grant G1000527), Jenner Investigator and Lister Institute Research Prize Fellow. He is a named inventor on patent applications covering malaria vaccines and immunization regimes. S Biswas is a NDM Leadership Fellow and Junior Research Fellow of St Catherine's College, Oxford University. The authors have no 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 214 TC 12 Z9 12 U1 3 U2 25 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-0584 EI 1744-8395 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD MAY PY 2015 VL 14 IS 5 BP 653 EP 680 DI 10.1586/14760584.2015.993383 PG 28 WC Immunology SC Immunology GA CF8JJ UT WOS:000352804000004 PM 25597923 ER PT J AU Wang, LH Lingappan, K Jiang, WW Couroucli, XI Welty, SE Shivanna, B Barrios, R Wang, GD Khan, MF Gonzalez, FJ Roberts, LJ Moorthy, B AF Wang, Lihua Lingappan, Krithika Jiang, Weiwu Couroucli, Xanthi I. Welty, Stephen E. Shivanna, Binoy Barrios, Roberto Wang, Gangduo Khan, M. Firoze Gonzalez, Frank J. Roberts, L. Jackson Moorthy, Bhagavatula TI Disruption of cytochrome P4501A2 in mice leads to increased susceptibility to hyperoxic lung injury SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Acute lung injury; CYP1A2; ARDS; Oxidative stress; Free radicals ID RESPIRATORY-DISTRESS-SYNDROME; POLYCYCLIC AROMATIC-HYDROCARBONS; OXIDATIVE STRESS; OXYGEN-TOXICITY; PREMATURE-INFANTS; GENE-EXPRESSION; NEWBORN MICE; IN-VIVO; INDUCTION; PULMONARY AB Hyperoxia contributes to acute lung injury in diseases such as acute respiratory distress syndrome. Cytochrome P450 (CYP) lA enzymes have been implicated in hyperoxic lung injury, but the mechanistic role of CYP1A2 in pulmonary injury is not known. We hypothesized that mice lacking the gene Cypl a2 (which is predominantly expressed in the liver) will be more sensitive to lung injury and inflammation mediated by hyperoxia and that CYP1A2 will play a protective role by attenuating lipid peroxidation and oxidative stress in the lung. Eight- to ten-week-old WT (C57BL/6) or Cyp1a2(-/-) mice were exposed to hyperoxia ( > 95% O-2) or maintained in room air for 24-72 h. Lung injury was assessed by determining the ratio of lung weight/body weight (LW/BW) and by histology. Extent of inflammation was determined by measuring the number of neutrophils in the lung as well as cytokine expression. The Cyp1a2(-/-) mice under hyperoxic conditions showed increased LW/BW ratios, lung injury, neutrophil infiltration, and IL-6 and TNF-alpha levels and augmented lipid peroxidation, as evidenced by increased formation of malondialdehyde- and 4-hydroxynonenal-protein adducts and pulmonary isofurans compared to WT mice. In vitro experiments showed that the F-2-isoprostane PGF(2)-alpha is metabolized by CYP1A2 to a dinor metabolite, providing evidence for a catalytic role for CYP1A2 in the metabolism of F-2-isoprostanes. In summary, our results support the hypothesis that hepatic CYP1A2 plays a critical role in the attenuation of hyperoxic lung injury by decreasing lipid peroxidation and oxidative stress in vivo. (C) 2015 Elsevier Inc. All rights reserved. C1 [Wang, Lihua; Lingappan, Krithika; Jiang, Weiwu; Couroucli, Xanthi I.; Welty, Stephen E.; Shivanna, Binoy; Moorthy, Bhagavatula] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Div Neonatal Perinatal Med, Houston, TX 77030 USA. [Barrios, Roberto] Houston Methodist Res Inst, Dept Pathol, Houston, TX 77030 USA. [Wang, Gangduo; Khan, M. Firoze] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Gonzalez, Frank J.] NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Roberts, L. Jackson] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37240 USA. RP Moorthy, B (reprint author), Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Div Neonatal Perinatal Med, Houston, TX 77030 USA. EM bmoorthy@bcm.edu FU National Institutes of Health [ES-009132, HL-112516, HL-087174, ES-019689, HL-088343]; Center for Translational Environmental Health Research [P30ES023512] FX This work was supported in part by funds from RO1 grants from the National Institutes of Health (ES-009132, HL-112516, HL-087174, and ES-019689) to B.M., HL-088343 to X.I.C., and the Center for Translational Environmental Health Research, P30ES023512. NR 65 TC 5 Z9 6 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY PY 2015 VL 82 BP 147 EP 159 DI 10.1016/j.freeradbiomed.2015.01.019 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CF8PF UT WOS:000352823700013 PM 25680282 ER PT J AU Liu, CY Chen, D Bluemke, DA Wu, CO Teixido-Tura, G Chugh, A Vasu, S Lima, JAC Hundley, WG AF Liu, Chia-Ying Chen, Doris Bluemke, David A. Wu, Colin O. Teixido-Tura, Gisela Chugh, Atul Vasu, Sujethra Lima, Joao A. C. Hundley, W. Gregory TI Evolution of Aortic Wall Thickness and Stiffness With Atherosclerosis Long-Term Follow Up From the Multi-Ethnic Study of Atherosclerosis SO HYPERTENSION LA English DT Article DE hypertension; magnetic resonance imaging; vascular stiffness ID INTIMA-MEDIA THICKNESS; CAROTID ARTERIES; RISK; AGE; DISTENSIBILITY; DISEASE; ADULTS; RACE; MRI; SEX AB The study was performed to determine age, sex, and time-dependent changes in aortic wall thickness (AWT) and to evaluate cross-sectional associations between AWT and arterial stiffness in older adults. Three hundred seventy-one longitudinal and 426 cross-sectional measurements of AWT from cardiovascular magnetic resonance imaging studies conducted within the Multi-Ethnic Study of Atherosclerosis were analyzed at 2 points in time, in 2000 to 2002 and then again from follow-up examinations in 2010 to 2012. Aortic wall thickness was determined from a double inversion recovery black-blood fast spin-echo sequence, and aortic stiffness was measured from a phase-contrast cine gradient echo sequence. The thickness of the midthoracic descending aortic wall was measured and correlated to distensibility of the ascending aorta and aortic pulse wave velocity. The average rate of AWT change was 0.032 mm/y. The increase in AWT was greater for those aged 45 to 54 years relative to individuals older than 55 years (P trend<0.001). Ascending aortic distensibility was lower (P<0.001) and pulse wave velocity was higher (P=0.012) for hypertensive subjects. After adjustment for traditional risk factors, distensibility of the ascending aorta was significantly related to AWT in participants without hypertension. Hypertension was associated with increased aortic stiffness independent of aortic wall thickness. C1 [Liu, Chia-Ying; Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Chen, Doris; Bluemke, David A.; Lima, Joao A. C.] Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA. [Wu, Colin O.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Teixido-Tura, Gisela] Univ Autonoma Barcelona, Dept Cardiol, Hosp Gen Univ Vall dHebron, E-08193 Barcelona, Spain. [Chugh, Atul] Univ Louisville, Sch Med, Div Cardiovasc Med, Louisville, KY 40292 USA. [Vasu, Sujethra; Hundley, W. Gregory] Wake Forest Univ, Dept Internal Med, Div Cardiovasc Med, Winston Salem, NC 27109 USA. RP Hundley, WG (reprint author), Wake Forest Hlth Sci, Div Cardiovasc Med, 1 Med Ctr Blvd, Winston Salem, NC 27157 USA. EM ghundley@wakehealth.edu OI Teixido-Tura, Gisela/0000-0003-4714-2420; Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [N01-HC-95165, N01-HC-95168]; [R01 HL076438] FX This research was supported by contracts N01-HC-95165, N01-HC-95168, from the National Heart, Lung, and Blood Institute and by grant R01 HL076438. NR 15 TC 3 Z9 3 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD MAY PY 2015 VL 65 IS 5 BP 1015 EP 1019 DI 10.1161/HYPERTENSIONAHA.114.05080 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CF4AJ UT WOS:000352490400095 PM 25776078 ER PT J AU Morris, BJ Willcox, BJ Tranah, GJ Chen, R Masaki, KH He, Q Willcox, DC Allsopp, R Moisyad, S Poon, LW Newman, AB Harris, TB Cummings, SR Liu, Y Parimi, N Evans, DS Donlon, TA AF Morris, B. J. Willcox, B. J. Tranah, G. J. Chen, R. Masaki, K. H. He, Q. Willcox, D. C. Allsopp, R. Moisyad, S. Poon, L. W. Newman, A. B. Harris, T. B. Cummings, S. R. Liu, Y. Parimi, N. Evans, D. S. Donlon, T. A. TI FOXO3 GENOTYPE INCREASES LIFESPAN BY A MAJOR EFFECT ON CARDIOVASCULAR MORTALITY SO HYPERTENSION LA English DT Meeting Abstract CT 36th Annual Scientific Meeting of the High-Blood-Pressure-Research-Council-of-Australia (HBPRCA) CY NOV 26-28, 2014 CL Adelaide, AUSTRALIA SP High Blood Pressure Res Council Australia C1 [Morris, B. J.; Chen, R.; Masaki, K. H.; He, Q.; Donlon, T. A.] Kuakini Med Ctr, Dept Res, Honolulu, HI USA. [Morris, B. J.; Masaki, K. H.] Univ Hawaii, John A Burns Sch Med, Dept Geriatr, Honolulu, HI 96822 USA. [Morris, B. J.] Univ Sydney, Sch Med Sci & Bosch Inst, Basic & Clin Genom Lab, Sydney, NSW 2006, Australia. [Tranah, G. J.; Cummings, S. R.; Parimi, N.; Evans, D. S.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Willcox, D. C.] Okinawa Int Univ, Dept Human Welf, Okinawa, Japan. [Allsopp, R.; Moisyad, S.] Univ Hawaii, Inst Biogenesis Res, Honolulu, HI 96822 USA. [Poon, L. W.] Univ Georgia, Inst Gerontol, Athens, GA 30602 USA. [Newman, A. B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Harris, T. B.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Liu, Y.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD MAY PY 2015 VL 65 IS 5 BP E29 EP E30 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CF4AJ UT WOS:000352490400018 ER PT J AU Rudy, BJ Kapogiannis, BG Worrell, C Squires, K Bethel, J Li, S Wilson, CM Agwu, A Emmanuel, P Price, G Hudey, S Goodenow, MM Sleasman, JW AF Rudy, Bret J. Kapogiannis, Bill G. Worrell, Carol Squires, Kathleen Bethel, James Li, Su Wilson, Craig M. Agwu, Allison Emmanuel, Patricia Price, Georgine Hudey, Stephanie Goodenow, Maureen M. Sleasman, John W. CA Adolescent Trials Network HIV AIDS TI Immune Reconstitution but Persistent Activation After 48 Weeks of Antiretroviral Therapy in Youth With Pre-Therapy CD4 > 350 in ATN 061 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adolescents; antiretroviral therapy; immune reconstitution; inflammation ID T-CELL-ACTIVATION; VIRUS-INFECTED PATIENTS; PATIENT-RELATED RISKS; HIV-INFECTION; MICROBIAL TRANSLOCATION; UNITED-STATES; VIRAL LOAD; THYMIC OUTPUT; ADOLESCENTS; RNA AB Background: Measures of immune outcomes in youth who initiate combination antiretroviral therapy (cART) early in HIV infection are limited. Design: Adolescent Trials Network 061 examined changes over 48 weeks of cART in T-cell subsets and markers of T-cell and macrophage activation in subjects with pre-therapy CD4. 350 cells/mm(3). All subjects had optimal viral suppression from weeks 24 through 48. Methods: Subjects (n = 48) initiated cART with tenofovir/emtricitabine plus ritonavir-boosted atazanavir. Data were collected at baseline and weeks 12, 24, and 48. Trends were compared to uninfected controls. Results: Significant increases over 48 weeks were noted in all CD4 populations, including total, naive, central memory (CM), and effector memory RO (EM RO) and effector memory RA (EM RA), whereas numbers of CM and EM RO CD8 cells declined significantly. By week 48, CD4 naive cells were similar to controls, whereas CM CD4 cells remained significantly lower and EM RO and EM RA subsets were significantly higher. CD38 and HLA DR expression, both individually and when co-expressed, decreased over 48 weeks of cART on CD8 cells but remained significantly higher than controls at week 48. In contrast, markers of macrophage activation measured by sCD14 and sCD163 in plasma did not change with cART and were significantly higher than controls. Conclusions: In youth initiating early cART, CD4 cell reconstitution is robust with decreases in CD8 cells. However, CD8 T-cell and macrophage activation persists at higher levels than uninfected controls. C1 [Rudy, Bret J.] NYU, Sch Med, New York, NY USA. [Kapogiannis, Bill G.; Worrell, Carol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Squires, Kathleen] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. [Bethel, James; Li, Su; Price, Georgine] Westat Corp, Rockville, MD USA. [Wilson, Craig M.] Univ Alabama Birmingham, Birmingham, AL USA. [Agwu, Allison] Johns Hopkins Sch Med, Baltimore, MD USA. [Emmanuel, Patricia; Hudey, Stephanie] Univ S Florida, Sch Med, Tampa, FL 33620 USA. [Goodenow, Maureen M.] Univ Florida, Hlth Sci Ctr, Gainesville, FL USA. [Sleasman, John W.] Duke Univ, Sch Med, Durham, NC USA. RP Rudy, BJ (reprint author), NYULMC Pediat, 145 E 32nd St,Room 1408, New York, NY 10016 USA. EM bret.rudy@nyumc.org FU PHS National Institute of Drug Abuse [DA031017]; Adolescent Trials Network for HIV/AIDS Interventions (ATN) from the National Institutes of Health through the Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 HD 040533, U01 HD 040474]; National Institute on Drug Abuse; National Institute on Mental Health; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Mental Health [U01 A1068632]; [R01 DA DA031017] FX Supported in part by PHS National Institute of Drug Abuse DA031017 and by The Adolescent Trials Network for HIV/AIDS Interventions (ATN) from the National Institutes of Health (U01 HD 040533 and U01 HD 040474) through the Eunice Kennedy Shriver National Institute of Child Health and Human Development (B.G.K.), with supplemental funding from the National Institutes on Drug Abuse (K. Davenny) and Mental Health (P. Brouwers and S. Allison). It was also supported by R01 DA DA031017 (M.M.G. and J.W.S.). The protocol was co-endorsed by the International Maternal Pediatric Adolescent AIDS Clinical Trials Group. Support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health (U01 A1068632). The study was scientifically reviewed by the ATN's Therapeutic Leadership Group. Network, scientific, and logistical support was provided by the ATN Coordinating Center (C.M.W. and C. Partlow) at The University of Alabama at Birmingham. Network operations and analytic support was provided by the ATN Data and Operations Center at Westat, Inc. (J. Korelitz, B. Driver, and G.P.). NR 53 TC 6 Z9 6 U1 0 U2 4 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 MAY 1 PY 2015 VL 69 IS 1 BP 52 EP 60 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CG1LE UT WOS:000353033300015 PM 25942459 ER PT J AU Raine, A Portnoy, J Liu, JH Mahoomed, T Hibbeln, JR AF Raine, Adrian Portnoy, Jill Liu, Jianghong Mahoomed, Tashneem Hibbeln, Joseph R. TI Reduction in behavior problems with omega-3 supplementation in children aged 8-16 years: a randomized, double-blind, placebo-controlled, stratified, parallel-group trial SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Omega-3; externalizing; internalizing; aggression; randomized trial ID PROACTIVE AGGRESSION QUESTIONNAIRE; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; BRAIN STRUCTURE ABNORMALITIES; YOUNG-ADULT PRISONERS; CONDUCT PROBLEMS; ANTISOCIAL-BEHAVIOR; UNEMOTIONAL TRAITS; ADOLESCENT BOYS; OMEGA-3-FATTY-ACIDS; PSYCHOPATHOLOGY AB BackgroundWhile limited evidence suggests that omega-3 supplementation may reduce antisocial behavior in children, studies have not reported on posttreatment follow-up and most treatment periods have been of short duration. This study tests the hypothesis that omega-3 supplementation over 6months will reduce behavior problems in children both at the end of treatment and at 6months post treatment. MethodsIn this randomized, double-blind, placebo-controlled, stratified, parallel-group trial, a community sample of 8-16year old children were randomized into a treatment group (N=100) and a placebo-control group (N=100). The supplementation consisted of a fruit drink containing 1g/day of omega-3 or a placebo consisting of the same fruit drink without omega-3. Participants, caregivers, and research assistants were blinded to group assignment. The primary outcome measures of externalizing and internalizing behavior problems were reported by both caregivers and their children in a laboratory setting at 0months (baseline), 6months (end of treatment) and 12months (6months post treatment), together with the secondary outcome measures of parental antisocial behavior. Data were analyzed on an intention-to-treat basis including all participants. Trial registration: ClinicalTrials.gov: ResultsSignificant groupxtime interactions were observed with the treatment group showing long-term improvements in child behavior problems. The average posttreatment effect size was d=-.59. Effects were documented for parent reports, but with the exception of proactive and reactive aggression, child-report data were nonsignificant. Parents whose children took omega-3 showed significant posttreatment reductions in their own antisocial and aggressive behavior. This improvement in caregiver behavior partly mediated the improvements observed in child behavior. ConclusionsFindings provide initial evidence that omega-3 supplementation can produce sustained reductions in externalizing and internalizing behavior problems. Results are the first to report improvements in caregiver behavior, and to establish this improvement as a part-mechanism for the efficacy of omega-3. C1 [Raine, Adrian; Portnoy, Jill] Univ Penn, Dept Criminol, Philadelphia, PA 19104 USA. [Raine, Adrian; Portnoy, Jill] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Raine, Adrian; Portnoy, Jill] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. [Liu, Jianghong] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Mahoomed, Tashneem] Joint Child Hlth Project, Quatre Bornes, Quatre Bornes, Mauritius. [Hibbeln, Joseph R.] NIAAA, Sect Nutr Neurosci, Bethesda, MD USA. RP Raine, A (reprint author), Univ Penn, Dept Criminol, 3809 Walnut St, Philadelphia, PA 19104 USA. EM araine@sas.upenn.edu FU Smartfish AA, Oslo, Norway; Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, Rockville, MD; University of Pennsylvania FX This study was made possible in part by funding from Smartfish AA, Oslo, Norway, who produced the omega-3 supplement and placebo drink used in this study. It was also supported in part by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, and the University of Pennsylvania. The authors wish to thank Shameem Oomur, Shameemah Golamnobee, and Joelle Rawoteea for their assistance in data collection. The authors have declared that they have no competing or potential conflicts of interest. NR 48 TC 13 Z9 13 U1 5 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD MAY PY 2015 VL 56 IS 5 BP 509 EP 520 DI 10.1111/jcpp.12314 PG 12 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA CF4YQ UT WOS:000352560900003 PM 25146492 ER PT J AU Shinomiya, K Tokura, K Kimura, E Takai, M Harikai, N Yoshida, K Yanagidaira, K Ito, Y AF Shinomiya, Kazufusa Tokura, Koji Kimura, Emiru Takai, Midori Harikai, Naoki Yoshida, Kazunori Yanagidaira, Kazuhiro Ito, Yoichiro TI Design of a coil satellite centrifuge and its performance on counter-current chromatographic separation of 4-methylumbelliferyl sugar derivatives with polar organic-aqueous two-phase solvent systems SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 8th International Conference on Countercurrent Chromatography (CCC) CY JUL 23-25, 2014 CL Uxbridge, ENGLAND DE Counter-current chromatography; Instrumentation; Coil satellite centrifuge; Partition efficiency; Separation of sugar derivatives ID PLANET CENTRIFUGE; ROTARY SEALS; APPARATUS; PROTEINS AB A new high-speed counter-current chromatograph, named coil satellite centrifuge (CSC), was designed and fabricated in our laboratory. The CSC apparatus produces the satellite motion such that the coiled column simultaneously rotates around the sun axis (the angular velocity, omega(1)), the planet axis (omega(2)) and the satellite axis (the central axis of the column) (omega(3)). In order to achieve this triplicate rotary motion without twisting of the flow tube, the rotation of each axis was determined by the following formula: omega(1) = omega(2) + omega(3). This relation enabled to lay out the flow tube without twisting by the simultaneous rotation of three axes. The flow tube was introduced from the bottom side of the apparatus into the sun axis of the first rotary frame reaching the upper side of the planet axis and connected to the column in the satellite axis. The performance of the apparatus was examined on separation of 4-methylumbelliferyl (MU) sugar derivatives as test samples with organic-aqueous two-phase solvent systems composed of ethyl acetate/1-butanol/water (3:2:5, v/v) for lower phase mobile and (1:4:5, v/v) for upper phase mobile. With lower phase mobile, five 4-MU sugar derivatives including beta-D-cellobioside (Cel), beta-D-glucopyranoside, alpha-D-mannopyranoside, beta-D-fucopyranoside and alpha-L-fucopyranoside (alpha-L-Fuc) were separated with the combined rotation around each axis at counterclockwise (CCW) (omega(1)) - CCW (omega(2)) - CCW (omega(3)) by the flow tube distribution. With upper phase mobile, three 4-MU sugar derivatives including alpha-L-Fuc, beta-D-galactopyranoside and Cel were separated with the combined rotation around each axis at clockwise (CW) (omega(1)) - CW (omega(2)) - CW (omega(3)) by the flow tube distribution. A series of experiments on peak resolution and stationary phase retention revealed that better partition efficiencies were obtained at the flow rate of 0.5 mL/min (column 1) and 0.8 mL/min (column 2) for lower phase mobile and 0.2 mL/min (column 1) and 0.4 mL/min (column 2) for upper phase mobile when using the left-handed multilayer coil (total capacity: 57.0 mL for column 1 and 75.0 mL for column 2) under the rotation speeds of approximately omega(1) =300 rpm, omega(2) = 150 rpm and omega(3) = 150 rpm. (C) 2015 Elsevier B.V. All rights reserved. C1 [Shinomiya, Kazufusa; Kimura, Emiru; Takai, Midori; Harikai, Naoki] Nihon Univ, Sch Pharm, Funabashi, Chiba 2748555, Japan. [Tokura, Koji; Yoshida, Kazunori; Yanagidaira, Kazuhiro] Nihon Univ, Coll Sci & Technol, Funabashi, Chiba 2748501, Japan. [Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Shinomiya, K (reprint author), Nihon Univ, Sch Pharm, 7-7-1 Narashinodai, Funabashi, Chiba 2748555, Japan. EM shinomiya.kazufusa@nihon-u.ac.jp FU Intramural NIH HHS [ZIA HL006022-04] NR 17 TC 3 Z9 3 U1 4 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 EI 1873-3778 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAY 1 PY 2015 VL 1392 BP 48 EP 55 DI 10.1016/j.chroma.2015.03.011 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA CG2CG UT WOS:000353081900006 PM 25805719 ER PT J AU Jahangir, E Lipworth, L Edwards, TL Kabagambe, EK Mumma, MT Mensah, GA Fazio, S Blot, WJ Sampson, UKA AF Jahangir, Eiman Lipworth, Loren Edwards, Todd L. Kabagambe, Edmond K. Mumma, Michael T. Mensah, George A. Fazio, Sergio Blot, William J. Sampson, Uchechukwu K. A. TI Smoking, sex, risk factors and abdominal aortic aneurysms: a prospective study of 18 782 persons aged above 65 years in the Southern Community Cohort Study SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID COST-EFFECTIVENESS; OLDER-ADULTS; WOMEN; PREVALENCE; HEALTH; MORTALITY; MEN; PROGRAM; TROMSO; TRIAL AB Background Abdominal aortic aneurysm (AAA) is a leading cause of death in the USA. We evaluated the incidence and predictors of AAA in a prospectively followed cohort. Methods We calculated age-adjusted AAA incidence rates (IR) among 18 782 participants aged >= 65 years in the Southern Community Cohort Study who received Medicare coverage from 1999-2012, and assessed predictors of AAA using multivariable Cox proportional hazards models, overall and stratified by sex, adjusting for demographic, lifestyle, socioeconomic, medical and other factors. HRs and 95% CIs were calculated for AAA in relation to factors ascertained at enrolment. Results Over a median follow-up of 4.94 years, 281 cases were identified. Annual IR was 153/100 000, 401, 354 and 174 among blacks, whites, men and women, respectively. AAA risk was lower among women (HR 0.48, 95% CI 0.36 to 0.65) and blacks (HR 0.51, 95% CI 0.37 to 0.69). Smoking was the strongest risk factor (former: HR 1.91, 95% CI 1.27 to 2.87; current: HR 5.55, 95% CI 3.67 to 8.40), and pronounced in women (former: HR 3.4, 95% CI 1.83 to 6.31; current: HR 9.17, 95% CI 4.95 to 17). A history of hypertension (HR 1.44, 95% CI 1.04 to 2.01) and myocardial infarction or coronary artery bypass surgery (HR 1.9, 95% CI 1.37 to 2.63) was negatively associated, whereas a body mass index > 25 kg/m(2) (HR 0.72; 95% CI 0.53 to 0.98) was protective. College education (HR 0.6, 95% CI 0.37 to 0.97) and black race (HR 0.44, 95% CI 0.28 to 0.67) were protective among men. Conclusions Smoking is a major risk factor for incident AAA, with a strong and similar association between men and women. Further studies are needed to evaluate benefits of ultrasound screening for AAA among women smokers. C1 [Jahangir, Eiman; Lipworth, Loren; Edwards, Todd L.; Kabagambe, Edmond K.; Blot, William J.; Sampson, Uchechukwu K. A.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. [Jahangir, Eiman] Univ Queensland, Sch Med, Ochsner Clin Sch, John Ochsner Heart & Vasc Inst, New Orleans, LA 70121 USA. [Mumma, Michael T.; Blot, William J.] Int Epidemiol Inst, Rockville, MD USA. [Mensah, George A.] NHLBI, NIH, Bethesda, MD 20892 USA. [Fazio, Sergio] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Ctr Prevent Cardiol, Portland, OR 97201 USA. [Sampson, Uchechukwu K. A.] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN USA. [Sampson, Uchechukwu K. A.] Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA. RP Jahangir, E (reprint author), Univ Queensland, Sch Med, Ochsner Clin Sch, John Ochsner Heart & Vasc Inst, 1514 Jefferson Highway, New Orleans, LA 70121 USA. EM ejahangir@ochsner.org RI Jahangir, Eiman/P-1053-2015 OI Jahangir, Eiman/0000-0001-6944-5321 FU Foundation for the National Institutes of Health [2T32HL007411-31]; National Institute of Health [HL106845, HL57986]; Pepsi Co [R01 CA092447] FX Funding Institution: Foundation for the National Institutes of Health. 2T32HL007411-31. National Institute of Health. HL106845 and HL57986. R01 CA092447. Pepsi Co NR 41 TC 9 Z9 9 U1 3 U2 10 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X EI 1470-2738 J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD MAY PY 2015 VL 69 IS 5 BP 481 EP 488 DI 10.1136/jech-2014-204920 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CF4TR UT WOS:000352545300012 PM 25563744 ER PT J AU Margolis, KL Evans, GW Schwartz, AV Fleg, J AF Margolis, Karen L. Evans, Gregory W. Schwartz, Ann V. Fleg, Jerome TI Intensive BP Control, Falls, and Fractures: Response to Jolobe (MS #17620) SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Letter C1 [Margolis, Karen L.] HealthPartners Inst Educ & Res, Minneapolis, MN 55440 USA. [Evans, Gregory W.] Wake Forest Sch Med, Winston Salem, NC USA. [Schwartz, Ann V.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Fleg, Jerome] NHLBI, Bethesda, MD 20892 USA. RP Margolis, KL (reprint author), HealthPartners Inst Educ & Res, Box 1524,Mailstop 23301A, Minneapolis, MN 55440 USA. EM karen.l.margolis@healthpartners.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2015 VL 30 IS 5 BP 547 EP 547 DI 10.1007/s11606-015-3191-z PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CF7CJ UT WOS:000352713400007 PM 25650261 ER PT J AU Chawla, N Urato, M Ambs, A Schussler, N Hays, RD Clauser, SB Zaslavsky, AM Walsh, K Schwartz, M Halpern, M Gaillot, S Goldstein, EH Arora, NK AF Chawla, Neetu Urato, Matthew Ambs, Anita Schussler, Nicola Hays, Ron D. Clauser, Steven B. Zaslavsky, Alan M. Walsh, Kayo Schwartz, Margot Halpern, Michael Gaillot, Sarah Goldstein, Elizabeth H. Arora, Neeraj K. TI Unveiling SEER-CAHPSA (R): A New Data Resource for Quality of Care Research SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient experiences; cancer; chronic disease; data linkage; Medicare claims; quality of care; CAHPS; SEER registry ID MEDICARE CONSUMER ASSESSMENT; HEALTH-CARE; PATIENT EXPERIENCES; MULTILEVEL FACTORS; BENEFICIARIES; CONTINUUM; PROVIDERS AB Since 1990, the National Cancer Institute (NCI) and Centers for Medicare and Medicaid Services (CMS) have collaborated to create linked data resources to improve our understanding of patterns of care, health care costs, and trends in utilization. However, existing data linkages have not included measures of patient experiences with care. To describe a new resource for quality of care research based on a linkage between the Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPSA (R)) patient surveys and the NCI's Surveillance, Epidemiology and End Results (SEER) data. This is an observational study of CAHPS respondents and includes both fee-for-service and Medicare Advantage beneficiaries with and without cancer. The data linkage includes: CAHPS survey data collected between 1998 and 2010 to assess patient reports on multiple aspects of their care, such as access to needed and timely care, doctor communication, as well as patients' global ratings of their personal doctor, specialists, overall health care, and their health plan; SEER registry data (1973-2007) on cancer site, stage, treatment, death information, and patient demographics; and longitudinal Medicare claims data (2002-2011) for fee-for-service beneficiaries on utilization and costs of care. In total, 150,750 respondents were in the cancer cohort and 571,318 were in the non-cancer cohort. The data linkage includes SEER data on cancer site, stage, treatment, death information, and patient demographics, in addition to longitudinal data from Medicare claims and information on patient experiences from CAHPS surveys. Sizable proportions of cases from common cancers (e.g., breast, colorectal, prostate) and short-term survival cancers (e.g., pancreas) by time since diagnosis enable comparisons across the cancer care trajectory by MA vs. FFS coverage. SEER-CAHPS is a valuable resource for information about Medicare beneficiaries' experiences of care across different diagnoses and treatment modalities, and enables comparisons by type of insurance. C1 [Chawla, Neetu; Ambs, Anita; Arora, Neeraj K.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20892 USA. [Urato, Matthew; Schwartz, Margot; Halpern, Michael] RTI Int, Res Triangle Pk, NC USA. [Schussler, Nicola] Informat Management Serv Inc, Calverton, MD USA. [Hays, Ron D.] Univ Calif Los Angeles, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90024 USA. [Clauser, Steven B.] Patient Ctr Outcomes Res Inst, Washington, DC USA. [Zaslavsky, Alan M.; Walsh, Kayo] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Gaillot, Sarah; Goldstein, Elizabeth H.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. RP Chawla, N (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,3E450, Rockville, MD 20892 USA. EM neetu.chawla@nih.gov FU Indian Health Service in Alaska [Y1-PC-0064]; Connecticut Department of Public Health [HHSN261201000024C]; Emory University [HSN261201000025C]; University of Iowa [HHSN261201000032C]; University of Medicine and Dentistry of New Jersey [HHSN261201000027C]; University of Utah [HHSN261201000026C]; Cancer Prevention Institute of California [HHSN261201000140C]; University of Hawaii [HHSN261201000037C]; University of New Mexico [HHSN261201000033C]; Public Health Institute [HHSN261201000034C]; University of Southern California [HHSN261201000035C]; Fred Hutchinson Cancer Research Center [HHSN261201000029C]; University of Kentucky Research Foundation [HHSN261201000031C]; Wayne State University [HHSN261201000028C]; Louisiana State University Health Sciences Center [HHSN261201000030C] FX SEER is supported by an interagency agreement with Indian Health Service in Alaska (No. Y1-PC-0064) and the following contract agreements: Connecticut Department of Public Health (No. HHSN261201000024C); Emory University (No. HSN261201000025C); University of Iowa (No. HHSN261201000032C); University of Medicine and Dentistry of New Jersey (No. HHSN261201000027C); University of Utah (No. HHSN261201000026C); Cancer Prevention Institute of California (No. HHSN261201000140C); University of Hawaii (No. HHSN261201000037C); University of New Mexico (No. HHSN261201000033C); Public Health Institute (No. HHSN261201000034C); University of Southern California (No. HHSN261201000035C); Fred Hutchinson Cancer Research Center (No. HHSN261201000029C); University of Kentucky Research Foundation (No. HHSN261201000031C); Wayne State University (No. HHSN261201000028C); and Louisiana State University Health Sciences Center (No. HHSN261201000030C). Data from this paper was presented at the Academy Health Annual Research Meeting on June 8-10, 2014. NR 25 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2015 VL 30 IS 5 BP 641 EP 650 DI 10.1007/s11606-014-3162-9 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CF7CJ UT WOS:000352713400020 PM 25586868 ER PT J AU Wendler, D AF Wendler, David TI "Targeted" Consent for Pragmatic Clinical Trials SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE informed consent; pragmatic trials; research; standard care ID CHOICE AB Research on interventions within the standard of care has enormous potential, yet it also raises several ethical and regulatory challenges. Perhaps the most important is determining what consent process is needed for these "pragmatic" clinical trials. Some argue that pragmatic clinical trials need to obtain in-depth research consent. This approach ensures that patients are informed, but may introduce substantial selection bias and disruption of clinical care. Others argue that trials limited to interventions within the standard of care do not need to obtain research consent at all. While this approach avoids the problems with in-depth consent, it results in patients not knowing whether they are in research. The present manuscript proposes a way to avoid both sets of concerns. It argues that consent for research needs to supplement appropriate consent for standard care only to the extent that the research differs from standard care. Hence, pragmatic trials designed to mirror clinical care can obtain consent with only minimal additions to consent for standard care. This conclusion suggests that it may be possible for many pragmatic trials to obtain consent that is ethically appropriate, satisfies research regulations, and does not introduce substantial selection bias or clinical disruption. C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov FU NIH Clinical Center intramural funds FX This work was supported by NIH Clinical Center intramural funds. The views expressed herein are solely those of the author, and do not represent the position or policy of the NIH or the U.S. government. NR 13 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2015 VL 30 IS 5 BP 679 EP 682 DI 10.1007/s11606-014-3169-2 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CF7CJ UT WOS:000352713400028 PM 25586870 ER PT J AU Cataisson, C Kitagawa, H Hollander, C Dennis, PA Yuspa, SH AF Cataisson, C. Kitagawa, H. Hollander, C. Dennis, P. A. Yuspa, S. H. TI Rapamycin is a chemopreventive and chemotherapeutic agent for RAS-driven epidermal squamous cell carcinoma: Evidence from mouse models SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Cataisson, C.; Hollander, C.; Yuspa, S. H.] NCI, Bethesda, MD 20892 USA. [Kitagawa, H.; Dennis, P. A.] Johns Hopkins Bayview, Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 137 BP S23 EP S23 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200138 ER PT J AU DiGiovanna, JJ Tamura, D Merideth, M Khan, SG Angra, D Kraemer, KH AF DiGiovanna, J. J. Tamura, D. Merideth, M. Khan, S. G. Angra, D. Kraemer, K. H. TI Premature menopause and hematologic neoplasms further characterize xeroderma pigmentosum as a disorder of accelerated aging SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [DiGiovanna, J. J.; Tamura, D.; Khan, S. G.; Angra, D.; Kraemer, K. H.] NCI, Dermatol Branch, Bethesda, MD 20892 USA. [Merideth, M.] NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 112 BP S19 EP S19 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200113 ER PT J AU Elder, JT Tsoi, LC Iyer, MK Stuart, PE Swindell, WR Gudjonsson, JE Tejasvi, T Sarkar, MK Li, B Ding, J Voorhees, JJ Kang, HM Nair, RP Chinnaiyan, AM Abecasis, G AF Elder, J. T. Tsoi, L. C. Iyer, M. K. Stuart, P. E. Swindell, W. R. Gudjonsson, J. E. Tejasvi, T. Sarkar, M. K. Li, B. Ding, J. Voorhees, J. J. Kang, H. M. Nair, R. P. Chinnaiyan, A. M. Abecasis, G. TI Analysis of long non-coding RNAs highlights tissue-specific expression patterns and epigenetic profiles in normal and psoriatic skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Elder, J. T.; Stuart, P. E.; Swindell, W. R.; Gudjonsson, J. E.; Tejasvi, T.; Sarkar, M. K.; Voorhees, J. J.; Nair, R. P.] Univ Michigan, Dermatol, Ann Arbor, MI 48109 USA. [Elder, J. T.; Tejasvi, T.] Ann Arbor VA Hosp, Ann Arbor, MI USA. [Tsoi, L. C.; Kang, H. M.; Abecasis, G.] Univ Michigan, Biostat, Ann Arbor, MI 48109 USA. [Iyer, M. K.] Univ Michigan, Bioinformat, Ann Arbor, MI 48109 USA. [Li, B.] Vanderbilt Univ, Nashville, TN 37235 USA. [Ding, J.] NIH, Bethesda, MD 20892 USA. [Chinnaiyan, A. M.] Univ Michigan, Pathol, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 440 BP S75 EP S75 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200440 ER PT J AU Gaiser, MR Daily, K Brownell, I AF Gaiser, M. R. Daily, K. Brownell, I. TI Blood levels of neuron specific enolase, chromogranin A, and circulating tumor cells as Merkel cell carcinoma biomarkers SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Daily, K.; Brownell, I.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Gaiser, M. R.] Heidelberg Univ, Dept Dermatol, Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 241 BP S41 EP S41 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200242 ER PT J AU Glatz, M Polley, EC Simpson, EL Kong, HH AF Glatz, M. Polley, E. C. Simpson, E. L. Kong, H. H. TI Emollient therapy alters skin barrier and microbes in infants at risk for developing atopic dermatitis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Glatz, M.; Kong, H. H.] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Polley, E. C.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Simpson, E. L.] Oregon Hlth & Sci Univ, Dermatol, Portland, OR 97201 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 180 BP S31 EP S31 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200181 ER PT J AU Kim, J Nagato, G Ogawa, Y Udey, MC Morasso, M AF Kim, J. Nagato, G. Ogawa, Y. Udey, M. C. Morasso, M. TI Keratinocytes devoid of DLX3 initiate psoriasis-like inflammation in mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Kim, J.; Morasso, M.] NIAMS, NIH, Bethesda, MD USA. [Nagato, G.; Ogawa, Y.; Udey, M. C.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 669 BP S116 EP S116 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200669 ER PT J AU Kobayashi, T Glatz, M Horiuchi, K Doebel, T Kaplan, D Kong, HH Amagai, M Nagao, K AF Kobayashi, T. Glatz, M. Horiuchi, K. Doebel, T. Kaplan, D. Kong, H. H. Amagai, M. Nagao, K. TI Dysbiotic microbiota drives atopic inflammation in Adam17(fl/fl)Sox9-Cre mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Kobayashi, T.; Amagai, M.; Nagao, K.] Keio Univ, Sch Med, Dermatol, Tokyo, Japan. [Kobayashi, T.; Glatz, M.; Doebel, T.; Kong, H. H.; Nagao, K.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Horiuchi, K.] Keio Univ, Sch Med, Orthoped Surg, Tokyo, Japan. [Kaplan, D.] Univ Minnesota, Ctr Immunol, Dermatol, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 508 BP S87 EP S87 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200508 ER PT J AU Li, L Cataisson, C Flowers, B Michalowski, A Yuspa, SH AF Li, L. Cataisson, C. Flowers, B. Michalowski, A. Yuspa, S. H. TI Comparative evaluation of gene expression induced by RAS oncogenic alleles in mouse and human keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Li, L.; Cataisson, C.; Flowers, B.; Michalowski, A.; Yuspa, S. H.] NCI, CCR, LCBG, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 153 BP S26 EP S26 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200154 ER PT J AU Li, S Klover, P Thangapazham, RL Wang, J Moss, J Darling, TN AF Li, S. Klover, P. Thangapazham, R. L. Wang, J. Moss, J. Darling, T. N. TI MCP-1 is overexpressed by Tsc2-null skin fibroblasts in a mouse model of tuberous sclerosis with targeted disruption of Tsc2 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Li, S.; Klover, P.; Thangapazham, R. L.; Wang, J.; Darling, T. N.] Uniformed Serv Univ Hlth Sci, Dermatol, Bethesda, MD 20814 USA. [Moss, J.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 441 BP S76 EP S76 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200441 ER PT J AU Naik, HB Natarajan, B Salahuddin, T Ng, Q Doveikis, J Playford, M Lockshin, B Kaplan, M Gelfand, J Mehta, NN AF Naik, H. B. Natarajan, B. Salahuddin, T. Ng, Q. Doveikis, J. Playford, M. Lockshin, B. Kaplan, M. Gelfand, J. Mehta, N. N. TI Psoriasis area severity index score positively associates with vascular inflammation by FDG PET/CT SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Naik, H. B.] NCI, Dermatol Branch, Bethesda, MD 20892 USA. [Naik, H. B.; Natarajan, B.; Salahuddin, T.; Ng, Q.; Doveikis, J.; Mehta, N. N.] NHLBI, Sect Inflammat & Cardiometab Dis, Bethesda, MD 20892 USA. [Playford, M.; Lockshin, B.] DermAssociates, Silver Spring, MD USA. [Kaplan, M.] NIAMSD, Syst Autoimmun Branch, Bethesda, MD 20892 USA. [Gelfand, J.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 203 BP S35 EP S35 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200204 ER PT J AU Nathan, N Wang, J Li, S Cowen, EW Haughey, M Moss, J Darling, TN AF Nathan, N. Wang, J. Li, S. Cowen, E. W. Haughey, M. Moss, J. Darling, T. N. TI Oral sirolimus improves tuberous sclerosis complex skin tumors without evidence of resistance SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Nathan, N.; Wang, J.; Li, S.; Darling, T. N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. [Nathan, N.; Haughey, M.; Moss, J.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Cowen, E. W.] NIH, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 168 BP S29 EP S29 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200169 ER PT J AU Palazzo, E Kellett, MD Cataisson, C Gormley, A Bible, P Pietroni, V Radoja, N Hwang, J Blumenberg, M Yuspa, SH Morasso, M AF Palazzo, E. Kellett, M. D. Cataisson, C. Gormley, A. Bible, P. Pietroni, V. Radoja, N. Hwang, J. Blumenberg, M. Yuspa, S. H. Morasso, M. TI DLX3-dependent p53 signaling network controls keratinocyte cell cycle and squamous tumor growth SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Palazzo, E.; Kellett, M. D.; Gormley, A.; Bible, P.; Pietroni, V.; Radoja, N.; Hwang, J.; Morasso, M.] NIH, Skin Biol Lab, Bethesda, MD 20892 USA. [Cataisson, C.; Yuspa, S. H.] NIH, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Blumenberg, M.] NYU, Dept Dermatol, New York, NY 10016 USA. RI Palazzo, Elisabetta/J-5287-2016 OI Palazzo, Elisabetta/0000-0002-0812-5524 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 097 BP S17 EP S17 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200098 ER PT J AU Pichard, D Cardones, A Chu, E Kong, HH AF Pichard, D. Cardones, A. Chu, E. Kong, H. H. TI Patients with sorafenib induced drug eruptions can be successfully re-challenged SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Pichard, D.; Kong, H. H.] NCI, Dermatol Branch, CCR, NIH, Bethesda, MD 20892 USA. [Cardones, A.] Duke Univ, Dermatol, Durham, NC USA. [Chu, E.] Univ Penn, Dermatol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 240 BP S41 EP S41 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200241 ER PT J AU Scharschmidt, TC Vasquez, KS Truong, H Gearty, SV Pauli, ML Nosbaum, A Otto, M Moon, JJ Abbas, AK Fischbach, MA Rosenblum, MD AF Scharschmidt, T. C. Vasquez, K. S. Truong, H. Gearty, S. V. Pauli, M. L. Nosbaum, A. Otto, M. Moon, J. J. Abbas, A. K. Fischbach, M. A. Rosenblum, M. D. TI A wave of regulatory T cells into neonatal skin mediates tolerance to commensal microbes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Scharschmidt, T. C.; Vasquez, K. S.; Truong, H.; Gearty, S. V.; Pauli, M. L.; Nosbaum, A.; Rosenblum, M. D.] UCSF, Dermatol, San Francisco, CA USA. [Abbas, A. K.] UCSF, Pathol, San Francisco, CA USA. [Fischbach, M. A.] UCSF, Bioengn, San Francisco, CA USA. [Otto, M.] NIAID, Bethesda, MD 20892 USA. [Moon, J. J.] MGH, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 011 BP S2 EP S2 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200012 ER PT J AU Tom, W Eichenfield, LF Playford, M Admani, S Natarajan, B Mehta, NN AF Tom, W. Eichenfield, L. F. Playford, M. Admani, S. Natarajan, B. Mehta, N. N. TI Characterization of lipoprotein composition and function in pediatric psoriasis reveals a more atherogenic profile SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Tom, W.; Eichenfield, L. F.; Admani, S.] Univ Calif San Diego, Pediat & Med Dermatol, San Diego, CA 92103 USA. [Tom, W.; Eichenfield, L. F.; Admani, S.] Rady Childrens Hosp, San Diego, CA USA. [Playford, M.; Natarajan, B.; Mehta, N. N.] NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 219 BP S38 EP S38 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200220 ER PT J AU Yang, C Pomerantz, H Corwin, J Weinstock, MA Fleckman, P DiGiovanna, JJ Robinson-Bostom, L AF Yang, C. Pomerantz, H. Corwin, J. Weinstock, M. A. Fleckman, P. DiGiovanna, J. J. Robinson-Bostom, L. TI Skin histopathology from patients with X-linked recessive ichthyosis and autosomal recessive congenital ichthyosis with transglutaminase 1 mutation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 06-09, 2015 CL Atlanta, GA SP Soc Investigat Dermatol C1 [Yang, C.; Robinson-Bostom, L.] Brown Univ, Alpert Med Sch, Dermatol, Providence, RI 02912 USA. [Pomerantz, H.; Weinstock, M. A.] VA Med Ctr, Dermatoepidemiol, Providence, RI USA. [Corwin, J.] Vacaville Med Ctr, Dermatol, Vacaville, CA USA. [Fleckman, P.] Univ Washington, Dermatol, Seattle, WA 98195 USA. [DiGiovanna, J. J.] NCI NIH, Dermatol, CCR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2015 VL 135 SU 1 MA 195 BP S34 EP S34 PG 1 WC Dermatology SC Dermatology GA CF8CO UT WOS:000352783200196 ER PT J AU Butcher, M Fwu, C Kirkali, Z Kohler, T Burrows, P Eggers, P Kusek, J McVary, K AF Butcher, M. Fwu, C. Kirkali, Z. Kohler, T. Burrows, P. Eggers, P. Kusek, J. McVary, K. TI SEXUAL FUNCTION ASSOCIATED WITH LOWER URINARY TRACT SYMPTOMS IN MEN WITH BENIGN PROSTATIC HYPERPLASIA: MTOPS COHORT OF CROSS-SECTIONAL AND LONGITUDINAL DATA SO JOURNAL OF SEXUAL MEDICINE LA English DT Meeting Abstract C1 [Butcher, M.] So Illinois Univ, Carbondale, IL 62901 USA. [Fwu, C.] Social & Sci Syst Inc, Silver Spring, MD USA. [Kirkali, Z.; Eggers, P.; Kusek, J.] NIDDK, Div Kideny Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. [Kohler, T.; McVary, K.] So Illinois Univ, Dept Urol, Springfield, IL USA. [Burrows, P.] George Washington Univ, Ctr Biostat, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 EI 1743-6109 J9 J SEX MED JI J. Sex. Med. PD MAY PY 2015 VL 12 SU 2 SI SI MA 042 BP 116 EP 116 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CF8EQ UT WOS:000352789100043 ER PT J AU Clemens, JQ Clauw, DJ Kreder, K Krieger, JN Kusek, JW Lai, HH Rodriguez, L Williams, DA Hou, XL Stephens, A Landis, JR AF Clemens, J. Quentin Clauw, Daniel J. Kreder, Karl Krieger, John N. Kusek, John W. Lai, H. Henry Rodriguez, Larissa Williams, David A. Hou, Xiaoling Stephens, Alisa Landis, J. Richard CA MAPP Res Network TI Comparison of Baseline Urological Symptoms in Men and Women in the MAPP Research Cohort SO JOURNAL OF UROLOGY LA English DT Article DE cystitis; interstitial; prostatitis; pelvic pain; chronic pain ID PELVIC PAIN SYNDROME; INTERSTITIAL CYSTITIS EPIDEMIOLOGY; RANDOMIZED-CONTROLLED-TRIAL; CHRONIC PROSTATITIS; RESEARCH NETWORK; INDEX; PREVALENCE; CLASSIFICATION; PREDICTORS; SEVERITY AB Purpose: The clinical features of the interstitial cystitis/bladder pain syndrome are similar to those of the chronic prostatitis/chronic pelvic pain syndrome. However, to our knowledge no studies have directly compared the characteristics of these syndromes in men and women. Materials and Methods: The MAPP Research Network recruited 191 men and 233 women with IC/BPS or CP/CPPS. Baseline data included demographics, Interstitial Cystitis Symptom Index and Problem Index scores; Genitourinary Pain Index score; American Urological Association Symptom Index score; Likert scales to assess urinary urgency, frequency, pain and overall symptom severity; and a single question about the most bothersome pelvic symptom. Results: After adjustment for age, income and symptom duration, measures of pain severity were similar across genders. Mean scores for the ICSI, ICPI and AUASI were significantly higher in women than in men, reflecting more bladder focused symptoms in women. The most bothersome single symptom in men as well as in women was pain in the pubic/bladder area (men 34%, women 58%). The characteristics of the men and women in the MAPP cohort were similar to those reported in other research cohorts for IC/BPS and CP/CPPS. Conclusions: Our findings indicate that pain severity is similar for both genders and that bladder focused symptoms (urgency, suprapubic pain, frequency) are more common in women. However, a substantial proportion of men also reported these types of bladder symptoms. C1 [Clemens, J. Quentin; Clauw, Daniel J.; Williams, David A.] Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. [Kreder, Karl] Univ Iowa, Iowa City, IA USA. [Krieger, John N.] Univ Washington, Seattle, WA 98195 USA. [Kusek, John W.] NIDDK, Bethesda, MD 20892 USA. [Lai, H. Henry] Washington Univ, St Louis, MO USA. [Rodriguez, Larissa] Univ Calif Los Angeles, Los Angeles, CA USA. [Hou, Xiaoling; Stephens, Alisa; Landis, J. Richard] Univ Penn, Philadelphia, PA 19104 USA. RP Clauw, DJ (reprint author), Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [DK82370, DK82342, DK82315, DK82344, DK82325, DK82345, DK82333, DK82316]; Pfizer; Forest; Eli Lilly; Pierre Fabre; Cypress Bioscience; Wyeth; UCB; Astra Zeneca; Merck; J J; Nuvo; Jazz; Abbott; Cerephex; Iroko; Tonix; Theravance; IMC; Zynerba; Samumed; Medtronic; Tengion; Symptelligence; Health Focus FX Funding for the MAPP Research Network was obtained under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (DK82370, DK82342, DK82315, DK82344, DK82325, DK82345, DK82333 and DK82316.); Financial interest and/or other relationship with Pfizer, Forest, Eli Lilly, Pierre Fabre, Cypress Bioscience, Wyeth, UCB, Astra Zeneca, Merck, J & J, Nuvo, Jazz, Abbott, Cerephex, Iroko, Tonix, Theravance, IMC, Zynerba and Samumed.; Financial interest and/or other relationship with Medtronic, Tengion and Symptelligence.; Financial interest and/or other relationship with Medtronic.; Financial interest and/or other relationship with Health Focus. NR 25 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD MAY PY 2015 VL 193 IS 5 BP 1554 EP 1558 DI 10.1016/j.juro.2014.11.016 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA CG2OD UT WOS:000353113200032 PM 25463989 ER PT J AU Reinartz, MT Kalble, S Wainer, IW Seifert, R AF Reinartz, Michael T. Kaelble, Solveig Wainer, Irving W. Seifert, Roland TI Interaction of fenoterol stereoisomers with beta(2)-adrenoceptor-G(s)alpha fusion proteins: antagonist and agonist competition binding SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE beta(2)-adrenergic receptor; Structure-bias relationships; Functional selectivity; Fenoterol ID MOLECULAR-FIELD ANALYSIS; BETA(2)-ADRENERGIC RECEPTOR; STEREOCHEMISTRY; DERIVATIVES; LIGAND; CELLS; MODEL; CONFORMATIONS; EFFICIENCY; DOPAMINE AB The specific interaction between G-protein-coupled receptors and ligand is the starting point for downstream signaling. Fenoterol stereoisomers were successfully used to probe ligand-specific activation (functional selectivity) of the beta(2)-adrenoceptor (beta(2)AR) (Reinartz et al. 2015). In the present study, we extended the pharmacological profile of fenoterol stereoisomers using beta(2)AR-G(s)alpha fusion proteins in agonist and antagonist competition binding assays. Dissociations between binding affinities and effector potencies were found for (R,S')- and (S,S')-isomers of 4'-methoxy-1-naphthyl-fenoterol. Our data corroborate former studies on the importance of the aminoalkyl moiety of fenoterol derivatives for functional selectivity. C1 [Reinartz, Michael T.; Kaelble, Solveig; Seifert, Roland] Hannover Med Sch, Inst Pharmacol, D-30625 Hannover, Germany. [Wainer, Irving W.] NIA, Lab Clin Invest, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA. RP Seifert, R (reprint author), Hannover Med Sch, Inst Pharmacol, Carl Neuberg Str 1, D-30625 Hannover, Germany. EM seifert.roland@mh-hannover.de OI Reinartz, Michael/0000-0002-4211-4562 NR 27 TC 2 Z9 2 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-1298 EI 1432-1912 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAY PY 2015 VL 388 IS 5 BP 517 EP 524 DI 10.1007/s00210-015-1086-5 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CF8XU UT WOS:000352846200005 PM 25637582 ER PT J AU Baeck, A Kravitz, D Baker, C Op de Beeck, HP AF Baeck, Annelies Kravitz, Dwight Baker, Chris Op de Beeck, Hans P. TI Influence of lexical status and orthographic similarity on the multi-voxel response of the visual word form area SO NEUROIMAGE LA English DT Article DE Visual word form area; fMRI; Orthography; Lexicality ID HUMAN EXTRASTRIATE CORTEX; LEFT FUSIFORM GYRUS; VENTRAL STREAM; OCCIPITOTEMPORAL CORTEX; NEURAL BASIS; FMRI; PSEUDOWORDS; RECOGNITION; REPRESENTATIONS; ORGANIZATION AB Previous studies demonstrated that a region in the left fusiform gyrus, often referred to as the 'visual word form area' (VWFA), is responsive to written words, but the precise functional role of VWFA remains unclear. In the present study, we investigated the influence of orthographic similarity, and lexical factors on the multivoxel response patterns to written stimuli. Using high-resolution fMRI at 7 T, we compared the organization of visual word representations in VWFA to the organization in early visual cortex and a language region in the superior temporal gyrus. Sets of four letter words and pseudowords were presented, in which orthographic similarity was parametrically manipulated. We found that during a lexical decision task VWFA is responsive to the lexical status of a stimulus, but both real words and pseudowords were further processed in terms of orthographic similarity. In contrast, early visual cortex was only responsive to the visual aspects of the stimuli and in the left superior temporal gyrus there was an interaction between lexical status and orthography such that only real words were processed in terms of orthographic similarity. These findings indicate that VWFA represents the word/non-word status of letter strings as well as their orthographic similarity. (C) 2015 Elsevier Inc. All rights reserved. C1 [Baeck, Annelies; Op de Beeck, Hans P.] KULeuven, Univ Leuven, Lab Biol Psychol, B-3000 Leuven, Belgium. [Baeck, Annelies] KULeuven, Univ Leuven, Expt Psychol Lab, B-3000 Leuven, Belgium. [Baeck, Annelies; Kravitz, Dwight; Baker, Chris] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD USA. RP Baeck, A (reprint author), KULeuven, Univ Leuven, Lab Biol Psychol, Tiensestr 102, B-3000 Leuven, Belgium. EM Annelies.baeck@ppw.kuleuven.be; kravitzd@email.gwu.edu; bakerchris@mail.nih.gov; Hans.opdebeeck@ppw.kuleuven.be OI Baker, Chris/0000-0001-6861-8964 FU European Research Council [284101]; Intramural NIH HHS [Z01 MH002909-01]; NIMH NIH HHS [MH002909-07] NR 65 TC 1 Z9 1 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2015 VL 111 BP 321 EP 328 DI 10.1016/j.neuroimage.2015.01.060 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CF0HO UT WOS:000352224100030 PM 25665965 ER PT J AU Chen, JE Chang, C Greicius, MD Glover, GH AF Chen, Jingyuan E. Chang, Catie Greicius, Michael D. Glover, Gary H. TI Introducing co-activation pattern metrics to quantify spontaneous brain network dynamics SO NEUROIMAGE LA English DT Article DE Brain dynamics; Resting state networks; Co-activation patterns; Point process analysis; Working memory ID FUNCTIONAL CONNECTIVITY; RESTING STATE; FMRI AB Recently, fMRI researchers have begun to realize that the brain's intrinsic network patterns may undergo substantial changes during a single resting state (RS) scan. However, despite the growing interest in brain dynamics, metrics that can quantify the variability of network patterns are still quite limited. Here, we first introduce various quantification metrics based on the extension of co-activation pattern (CAP) analysis, a recently proposed point-process analysis that tracks state alternations at each individual time frame and relies on very fewassumptions; then apply these proposed metrics to quantify changes of brain dynamics during a sustained 2-backworking memory (WM) task compared to rest. We focus on the functional connectivity of two prominent RS networks, the default-mode network (DMN) and executive control network (ECN). We first demonstrate less variability of global Pearson correlations with respect to the two chosen networks using a sliding-window approach duringWMtask compared to rest; then we show that the macroscopic decrease in variations in correlations during a WM task is also well characterized by the combined effect of a reduced number of dominant CAPs, increased spatial consistency across CAPs, and increased fractional contributions of a few dominant CAPs. These CAP metrics may provide alternative and more straightforward quantitative means of characterizing brain network dynamics than time-windowed correlation analyses. (C) 2015 Elsevier Inc. All rights reserved. C1 [Chen, Jingyuan E.; Glover, Gary H.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Chen, Jingyuan E.] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA. [Chang, Catie] NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Greicius, Michael D.] Stanford Sch Med, Dept Neurol & Neurol Sci, Funct Imaging Neuropsychiat Disorders Lab, Stanford, CA 94305 USA. RP Chen, JE (reprint author), Lucas MRI S Ctr, MC 5488,1201 Welch Rd, Stanford, CA 94305 USA. EM cjy2010@stanford.edu FU NIH [P41 EB015891] FX The authors gratefully acknowledge Bernard Ng and William Shirer for providing the brain functional atlas (ROI499w), the NIH for funding support (P41 EB015891), and three anonymous reviewers for their constructive comments, which have substantially improved the quality of the manuscript. NR 30 TC 10 Z9 10 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2015 VL 111 BP 476 EP 488 DI 10.1016/j.neuroimage.2015.01.057 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CF0HO UT WOS:000352224100042 PM 25662866 ER PT J AU Saha, K Partilla, JS Lehner, KR Seddik, A Stockner, T Holy, M Sandtner, W Ecker, GF Sitte, HH Baumann, MH AF Saha, Kusumika Partilla, John S. Lehner, Kurt R. Seddik, Amir Stockner, Thomas Holy, Marion Sandtner, Walter Ecker, Gerhard F. Sitte, Harald H. Baumann, Michael H. TI 'Second-Generation' Mephedrone Analogs, 4-MEC and 4-MePPP, Differentially Affect Monoamine Transporter Function SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID HUMAN DOPAMINE TRANSPORTER; HUMAN SEROTONIN TRANSPORTER; CONSTITUENT 3,4-METHYLENEDIOXYPYROVALERONE MDPV; CHROMATOGRAPHY-MASS-SPECTROMETRY; BIOGENIC-AMINE TRANSPORTERS; PSYCHOACTIVE BATH SALTS; SYNTHETIC CATHINONES; METHYLENEDIOXYPYROVALERONE MDPV; NEUROTRANSMITTER TRANSPORTERS; TOXICOLOGICAL DETECTION AB The nonmedical use of synthetic cathinones is increasing on a global scale. 4-Methyl-N-methylcathinone (mephedrone) is a popular synthetic cathinone that is now illegal in the United States and other countries. Since the legislative ban on mephedrone, a number of 'second-generation' analogs have appeared in the street drug marketplace, including 4-methyl-N-ethylcathinone (4-MEC) and 4'-methyl-alpha-pyrrolidinopropiophenone (4-MePPP). Here we characterized the interactions of 4-MEC and 4-MePPP with transporters for 5-HT (SERT) and dopamine (DAT) using molecular, cellular, and whole-animal methods. In vitro transporter assays revealed that 4-MEC displays unusual 'hybrid' activity as a SERT substrate (ie, 5-HT releaser) and DAT blocker, whereas 4-MePPP is a blocker at both transporters but more potent at DAT. In vivo microdialysis experiments in rat brain demonstrated that 4-MEC (1-3 mg/kg, i.v.) produced large increases in extracellular 5-HT, small increases in dopamine, and minimal motor stimulation. In contrast, 4-MePPP (1-3 mg/kg, i.v.) produced selective increases in dopamine and robust motor stimulation. Consistent with its activity as a SERT substrate, 4-MEC evoked inward current in SERT-expressing Xenopus oocytes, whereas 4-MePPP was inactive in this regard. To examine drug-transporter interactions at the molecular level, we modeled the fit of 4-MEC and 4-MePPP into the binding pockets for DAT and SERT. Subtle distinctions in ligand-transporter binding were found that account for the differential effects of 4-MEC and 4-MePPP at SERT. Collectively, our results provide key information about the pharmacology of newly emerging mephedrone analogs, and give clues to structural requirements that govern drug selectivity at DAT vs SERT. C1 [Saha, Kusumika; Stockner, Thomas; Holy, Marion; Sandtner, Walter; Sitte, Harald H.] Med Univ Vienna, Ctr Physiol & Pharmacol, Inst Pharmacol, Vienna, Austria. [Partilla, John S.; Lehner, Kurt R.; Baumann, Michael H.] NIDA, Designer Drug Res Unit, IRP, NIH, Baltimore, MD 21224 USA. [Seddik, Amir; Ecker, Gerhard F.] Univ Vienna, Dept Pharmaceut Sci, Vienna, Austria. [Sitte, Harald H.] Med Univ Vienna, Ctr Addict Res & Sci, Vienna, Austria. RP Baumann, MH (reprint author), NIDA, Designer Drug Res Unit, IRP, NIH,DHHS, 333 Cassell Dr,Suite 4400, Baltimore, MD 21224 USA. EM mbaumann@mail.nih.gov RI Stockner, Thomas/A-9509-2014; OI Stockner, Thomas/0000-0002-7071-8283; Sitte, Harald/0000-0002-1339-7444 FU Austrian Research Fund/FWF [F3506, W1232]; NIDA, NIH [DA000523-07] FX This research was supported by the Austrian Research Fund/FWF grants F3506 and W1232 to HHS and the Intramural Research Program of the NIDA, NIH, grant DA000523-07 to MHB. NR 63 TC 13 Z9 13 U1 0 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2015 VL 40 IS 6 BP 1321 EP 1331 DI 10.1038/npp.2014.325 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CG0PI UT WOS:000352968100003 PM 25502630 ER PT J AU Williams, LE Oler, JA Fox, AS McFarlin, DR Rogers, GM Jesson, MAL Davidson, RJ Pine, DS Kalin, NH AF Williams, Lisa E. Oler, Jonathan A. Fox, Andrew S. McFarlin, Daniel R. Rogers, Gregory M. Jesson, Maria A. L. Davidson, Richard J. Pine, Daniel S. Kalin, Ned H. TI Fear of the Unknown: Uncertain Anticipation Reveals Amygdala Alterations in Childhood Anxiety Disorders SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID FACIAL EXPRESSIONS; BRAIN ACTIVATION; NEURAL RESPONSES; FUNCTIONAL MRI; CHILDREN; ADOLESCENTS; METAANALYSIS; DEPRESSION; REACTIVITY; AVERSION AB Children with anxiety disorders (ADs) experience persistent fear and worries that are highly debilitating, conferring risk for lifelong psychopathology. Anticipatory anxiety is a core clinical feature of childhood ADs, often leading to avoidance of uncertain and novel situations. Extensive studies in non-human animals implicate amygdala dysfunction as a critical substrate for early life anxiety. To test specific amygdala-focused hypotheses in preadolescent children with ADs, we used fMRI to characterize amygdala activation during uncertain anticipation and in response to unexpected stimuli. Forty preadolescent (age 8-12 years) children, 20 unmedicated AD patients and 20 matched controls completed an anticipation task during an fMRI scan. In the task, symbolic cues preceded fear or neutral faces, such that 'certain' cues always predicted the presentation of fear or neutral faces, whereas 'uncertain' cues were equally likely to be followed by fear or neutral faces. Both AD children and controls showed robust amygdala response to faces. In response to the uncertain cues, AD children had increased amygdala activation relative to controls. Moreover, in the AD children, faces preceded by an 'uncertain' cue elicited increased amygdala activation, as compared with the same faces following a 'certain' cue. Children with ADs experience distress both in anticipation of and during novel and surprising events. Our findings suggest that increased amygdala activation may have an important role in the generation of uncertainty-related anxiety. These findings may guide the development of neuroscientifically informed treatments aimed at relieving the suffering and preventing the lifelong disability associated with pediatric ADs. C1 [Williams, Lisa E.; Oler, Jonathan A.; Fox, Andrew S.; McFarlin, Daniel R.; Rogers, Gregory M.; Jesson, Maria A. L.; Davidson, Richard J.; Kalin, Ned H.] Univ Wisconsin, Dept Psychiat, Wisconsin Psychiat Inst & Clin, Madison, WI 53719 USA. [Williams, Lisa E.; Oler, Jonathan A.; Fox, Andrew S.; McFarlin, Daniel R.; Jesson, Maria A. L.; Davidson, Richard J.; Kalin, Ned H.] Univ Wisconsin, HealthEmot Res Inst, Madison, WI 53719 USA. [Williams, Lisa E.; Oler, Jonathan A.; Fox, Andrew S.; McFarlin, Daniel R.; Jesson, Maria A. L.; Kalin, Ned H.] Univ Wisconsin, Lane Neuroimaging Lab, Madison, WI 53719 USA. [Fox, Andrew S.; Davidson, Richard J.; Kalin, Ned H.] Univ Wisconsin, Ctr Investigating Hlth Minds, Madison, WI 53719 USA. [Fox, Andrew S.; Davidson, Richard J.; Kalin, Ned H.] Univ Wisconsin, Waisman Lab Brain Imaging & Behav, Madison, WI 53719 USA. [Davidson, Richard J.] Univ Wisconsin, Dept Psychol, Madison, WI 53719 USA. [Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. RP Williams, LE (reprint author), Univ Wisconsin, Dept Psychiat, Wisconsin Psychiat Inst & Clin, 6001 Res Pk Blvd, Madison, WI 53719 USA. EM lewilliams1@gmail.com FU National Institutes of Health [R21 MH092581] FX We acknowledge the assistance of Anna White and Travis Doran, and the staffs of the HealthEmotions Research Institute (HERI) and Lane Neuroimaging Laboratory. This work was supported by the National Institutes of Health grant R21 MH092581 (NHK and JAO). NR 50 TC 9 Z9 9 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2015 VL 40 IS 6 BP 1428 EP 1435 DI 10.1038/npp.2014.328 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CG0PI UT WOS:000352968100013 PM 25502633 ER PT J AU Holroyd, KB Adrover, MF Fuino, RL Bock, R Kaplan, AR Gremel, CM Rubinstein, M Alvarez, VA AF Holroyd, Kathryn B. Adrover, Martin F. Fuino, Robert L. Bock, Roland Kaplan, Alanna R. Gremel, Christina M. Rubinstein, Marcelo Alvarez, Veronica A. TI Loss of Feedback Inhibition via D2 Autoreceptors Enhances Acquisition of Cocaine Taking and Reactivity to Drug-Paired Cues SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID KNOCK-OUT MICE; STRIATAL DOPAMINE RELEASE; CHOLINERGIC INTERNEURONS; NUCLEUS-ACCUMBENS; DORSAL STRIATUM; RECEPTORS; IMPULSIVITY; ADDICTION; RATS; RESPONSES AB A prominent aspect of drug addiction is the ability of drug-associated cues to elicit craving and facilitate relapse. Understanding the factors that regulate cue reactivity will be vital for improving treatment of addictive disorders. Low availability of dopamine (DA) D2 receptors (D2Rs) in the striatum is associated with high cocaine intake and compulsive use. However, the role of D2Rs of nonstriatal origin in cocaine seeking and taking behavior and cue reactivity is less understood and possibly underestimated. D2Rs expressed by midbrain DA neurons function as autoreceptors, exerting inhibitory feedback on DA synthesis and release. Here, we show that selective loss of D2 autoreceptors impairs the feedback inhibition of DA release and amplifies the effect of cocaine on DA transmission in the nucleus accumbens (NAc) in vitro. Mice lacking D2 autoreceptors acquire a cued-operant self-administration task for cocaine faster than littermate control mice but acquire similarly for a natural reward. Furthermore, although mice lacking D2 autoreceptors were able to extinguish self-administration behavior in the absence of cocaine and paired cues, they exhibited perseverative responding when cocaine-paired cues were present. This enhanced cue reactivity was selective for cocaine and was not seen during extinction of sucrose self-administration. We conclude that low levels of D2 autoreceptors enhance the salience of cocaine-paired cues and can contribute to the vulnerability for cocaine use and relapse. C1 [Holroyd, Kathryn B.; Adrover, Martin F.; Fuino, Robert L.; Bock, Roland; Alvarez, Veronica A.] NIAAA, Sect Neuronal Struct, NIH, Bethesda, MD 20892 USA. [Gremel, Christina M.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. [Rubinstein, Marcelo] Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol, Buenos Aires, DF, Argentina. [Rubinstein, Marcelo] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Buenos Aires, DF, Argentina. RP Alvarez, VA (reprint author), NIAAA, Sect Neuronal Struct, NIH, 5625 Fishers Lane,MSC 9411, Bethesda, MD 20892 USA. EM alvarezva@mail.nih.gov RI Alvarez, Veronica /E-9745-2015; Bock, Roland/G-2982-2016; OI Alvarez, Veronica /0000-0003-2611-8675; Bock, Roland/0000-0002-8654-1080; Kaplan, Alanna/0000-0002-2612-4736; Holroyd, Kathryn/0000-0001-5884-9734 FU NIAAA; NINDS [ZIA-AA000421]; ANPCYT-Mincyt of Argentina; Universidad de Buenos Aires; Tourette Syndrome Association FX The authors declare no conflict of interest. This study was funded by the Intramural Programs of NIAAA (VAA) and NINDS ZIA-AA000421 (to VAA), and by the ANPCYT-Mincyt of Argentina (to MR), Universidad de Buenos Aires (to MR), and Tourette Syndrome Association (to MR). NR 39 TC 10 Z9 10 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2015 VL 40 IS 6 BP 1495 EP 1509 DI 10.1038/npp.2014.336 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CG0PI UT WOS:000352968100019 PM 25547712 ER PT J AU Kiris, E Burnett, JC Nuss, JE Wanner, LM Peyser, BD Du, HT Gomba, GY Kota, KP Panchal, RG Gussio, R Kane, CD Tessarollo, L Bavari, S AF Kiris, Erkan Burnett, James C. Nuss, Jonathan E. Wanner, Laura M. Peyser, Brian D. Du, Hao T. Gomba, Glenn Y. Kota, Krishna P. Panchal, Rekha G. Gussio, Rick Kane, Christopher D. Tessarollo, Lino Bavari, Sina TI Src Family Kinase Inhibitors Antagonize the Toxicity of Multiple Serotypes of Botulinum Neurotoxin in Human Embryonic Stem Cell-Derived Motor Neurons SO NEUROTOXICITY RESEARCH LA English DT Article DE Motor neurons; Human embryonic stem cells; Src inhibitors; Botulinum neurotoxins; Cell-based assay; Drug discovery ID TYROSINE PHOSPHORYLATION; SYNAPTIC-VESICLE; DIRECTED DIFFERENTIATION; CLOSTRIDIAL NEUROTOXINS; CATALYTIC DOMAIN; RECEPTOR; SNAP-25; BINDING; METALLOPROTEASE; STABILIZATION AB Botulinum neurotoxins (BoNTs), the causative agents of botulism, are potent inhibitors of neurotransmitter release from motor neurons. There are currently no drugs to treat BoNT intoxication after the onset of the disease symptoms. In this study, we explored how modulation of key host pathways affects the process of BoNT intoxication in human motor neurons, focusing on Src family kinase (SFK) signaling. Motor neurons derived from human embryonic stem (hES) cells were treated with a panel of SFK inhibitors and intoxicated with BoNT serotypes A, B, or E (which are responsible for > 95 % of human botulism cases). Subsequently, it was found that bosutinib, dasatinib, KX2-391, PP1, PP2, Src inhibitor-1, and SU6656 significantly antagonized all three of the serotypes. Furthermore, the data indicated that the treatment of hES-derived motor neurons with multiple SFK inhibitors increased the antagonistic effect synergistically. Mechanistically, the small molecules appear to inhibit BoNTs by targeting host pathways necessary for intoxication and not by directly inhibiting the toxins' proteolytic activity. Importantly, the identified inhibitors are all well-studied with some in clinical trials while others are FDA-approved drugs. Overall, this study emphasizes the importance of targeting host neuronal pathways, rather than the toxin's enzymatic components, to antagonize multiple BoNT serotypes in motor neurons. C1 [Kiris, Erkan] Geneva Fdn, Tacoma, WA 98402 USA. [Kiris, Erkan; Nuss, Jonathan E.; Wanner, Laura M.; Gomba, Glenn Y.; Kota, Krishna P.; Panchal, Rekha G.; Kane, Christopher D.; Bavari, Sina] US Army Med Res Inst Infect Dis, Dept Mol & Translat Sci, Frederick, MD 21702 USA. [Kiris, Erkan; Du, Hao T.; Tessarollo, Lino] NCI, Neural Dev Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. [Burnett, James C.] NCI, Leidos Biomed Res Inc, CDDG, Frederick, MD 21702 USA. [Burnett, James C.; Peyser, Brian D.; Gussio, Rick] NCI, CDDG, Dev Therapeut Program, Frederick, MD 21702 USA. [Kane, Christopher D.] Henry M Jackson Fdn, Bethesda, MD USA. [Kane, Christopher D.] USAMRMC, DoD Biotechnol High Performance Comp Software App, TATRC, Frederick, MD USA. RP Kiris, E (reprint author), Geneva Fdn, Tacoma, WA 98402 USA. EM erkan.kiris@nih.gov; sina.bavari.civ@mail.mil OI Peyser, Brian/0000-0002-3455-5181 FU Defense Threat Reduction Agency; National Institutes of Health [4R33AI101387 - 03]; National Cancer Institute (NCI), National Institutes of Health (NIH) [HHSN261200800001E]; Intramural Research Program of the NCI, Center for Cancer Research, NIH FX We are indebted to Drs. Esta Sterneck and Balamurugan Kuppusamy for their insightful discussion concerning SFK inhibitors. Also, we thank Rajarshi Guha for R functions to optimize beta for synergy calculations, and Veronica Soloveva for helpful discussion. This research was supported by grants from the Defense Threat Reduction Agency and National Institutes of Health (4R33AI101387 - 03). For JCB, this project has been funded in whole or in part with federal funds from the National Cancer Institute (NCI), National Institutes of Health (NIH), under contract no. HHSN261200800001E. LT has been supported by the Intramural Research Program of the NCI, Center for Cancer Research, NIH. NR 81 TC 5 Z9 5 U1 1 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1029-8428 EI 1476-3524 J9 NEUROTOX RES JI Neurotox. Res. PD MAY PY 2015 VL 27 IS 4 BP 384 EP 398 DI 10.1007/s12640-015-9526-z PG 15 WC Neurosciences SC Neurosciences & Neurology GA CF1IR UT WOS:000352298900003 PM 25782580 ER PT J AU Lan, Q Vermeulen, R Dai, YF Ren, DZ Hu, W Duan, HW Niu, Y Xu, J Fu, W Meliefste, K Zhou, BS Yang, JF Ye, M Jia, XW Meng, T Bin, P Kim, C Bassig, BA Hosgood, HD Silverman, D Zheng, YX Rothman, N AF Lan, Qing Vermeulen, Roel Dai, Yufei Ren, Dianzhi Hu, Wei Duan, Huawei Niu, Yong Xu, Jun Fu, Wei Meliefste, Kees Zhou, Baosen Yang, Jufang Ye, Meng Jia, Xiaowei Meng, Tao Bin, Ping Kim, Christopher Bassig, Bryan A. Hosgood, H. Dean, III Silverman, Debra Zheng, Yuxin Rothman, Nathaniel TI Occupational exposure to diesel engine exhaust and alterations in lymphocyte subsets SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID INFLAMMATORY RESPONSES; LUNG-CANCER; PERIPHERAL-BLOOD; HEALTHY HUMANS; AIRWAY; VOLUNTEERS; BIOMARKERS; MARKERS; MINERS AB Background The International Agency for Research on Cancer recently classified diesel engine exhaust (DEE) as a Group I carcinogen based largely on its association with lung cancer. However, the exposure-response relationship is still a subject of debate and the underlying mechanism by which DEE causes lung cancer in humans is not well understood. Methods We conducted a cross-sectional molecular epidemiology study in a diesel engine truck testing facility of 54 workers exposed to a wide range of DEE (ie, elemental carbon air levels, median range: 49.7, 6.1-107.7 mu g/m(3)) and 55 unexposed comparable controls. Results The total lymphocyte count (p=0.00044) and three of the four major lymphocyte subsets (ie, CD4+ T cells (p=0.00019), CD8+ T cells (p=0.0058) and B cells (p=0.017)) were higher in exposed versus control workers and findings were highly consistent when stratified by smoking status. In addition, there was evidence of an exposure-response relationship between elemental carbon and these end points (p(trends)<0.05), and CD4+ T cell levels were significantly higher in the lowest tertile of DEE exposed workers compared to controls (p=0.012). Conclusions Our results suggest that DEE exposure is associated with higher levels of cells that play a key role in the inflammatory process, which is increasingly being recognised as contributing to the aetiology of lung cancer. Impact This study provides new insights into the underlying mechanism of DEE carcinogenicity. C1 [Lan, Qing; Hu, Wei; Kim, Christopher; Bassig, Bryan A.; Hosgood, H. Dean, III; Silverman, Debra; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. [Vermeulen, Roel; Meliefste, Kees] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. [Dai, Yufei; Duan, Huawei; Niu, Yong; Ye, Meng; Jia, Xiaowei; Meng, Tao; Bin, Ping; Zheng, Yuxin] Chinese Ctr Dis Control & Prevent, Natl Inst Occupat Hlth & Poison Control, Key Lab Chem Safety & Hlth, Beijing, Peoples R China. [Ren, Dianzhi; Fu, Wei; Yang, Jufang] Chaoyang Ctr Dis Control & Prevent, Chaoyang, Peoples R China. [Xu, Jun] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Zhou, Baosen] China Med Univ, Shenyang 110001, Peoples R China. [Hosgood, H. Dean, III] Albert Einstein Coll Med, Div Epidemiol, New York, NY USA. RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Room 6E138, Rockville, MD 20850 USA. EM qingl@mail.nih.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU National Cancer Institute; National Institutes of Health FX This work was supported by intramural funds from the National Cancer Institute and the National Institutes of Health. NR 16 TC 4 Z9 4 U1 1 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD MAY PY 2015 VL 72 IS 5 BP 354 EP 359 DI 10.1136/oemed-2014-102556 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CG0UV UT WOS:000352987900007 PM 25673341 ER PT J AU Moseley, KF Chia, CW Simonsick, EM Egan, JM Ferrucci, L Sellmeyer, DE AF Moseley, K. F. Chia, C. W. Simonsick, E. M. Egan, J. M. Ferrucci, L. Sellmeyer, D. E. TI Sex-specific differences in progressive glucose intolerance and hip geometry: the Baltimore Longitudinal Study of Aging SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Bone architecture; Bone quality; Hip geometry; Type 2 diabetes ID TYPE-2 DIABETES-MELLITUS; BONE-MINERAL DENSITY; IMPAIRED FASTING GLUCOSE; FEMORAL-NECK STRENGTH; FRACTURE RISK; POSTMENOPAUSAL WOMEN; HEALTH; POPULATION; MORTALITY; BMD AB A Summary Fracture risk is increased in type 2 diabetes mellitus (T2DM). The effect of pre-diabetes and T2DM on bone macroarchitecture and strength has not been well investigated. In this study, we show that in women only, both pre-diabetes and T2DM are associated with decreased hip bending strength and mineralization which might lead to skeletal weakness. Introduction Older men and women with T2DM are at increased risk for fracture despite normal bone mineral density (BMD). The discordance between bone quantity and skeletal fragility has driven investigation into additional determinants of fracture resistance in T2DM. Additionally, the effect of pre-diabetes on bone strength has not been well described. The aim of this study was to determine differences in bone macroarchitecture and strength, measured by hip geometry, in persons with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. Methods We performed cross-sectional analyses of older (age > 55 years) men (n = 472) and women (n = 473) participating in the Baltimore Longitudinal Study of Aging (BLSA) classified as NGT, IGT, or T2DM based on oral glucose tolerance testing. Bone strength measures included the hip geometry parameters of section modulus (Z), cross-sectional area (CSA), and buckling ratio (BR). Sex-stratified analyses were conducted using adjusted stepwise regression models. Results In women, IGT and T2DM were negatively associated with hip geometry parameters including mineralization in cross section (CSA, -0.076 and -0.073, respectively; both p < 0.05) and hip bending strength (Z, -0.097 and -0.09, respectively; both p < 0.05); conversely, IGT and T2DM were associated with improved compressive strength (BR, -0.31 and -0.29, respectively; both p < 0.05). There was no significant association between glycemic status and hip geometry in men. Conclusions In women only, both IGT and T2DM were inversely associated with bone macroarchitecture and measures of bone mineralization and bending strength. The same association between worsening glycemic status and bone strength was not observed in men. These data suggest a differential effect of sex on hip geometry with evolving glucose intolerance. C1 [Moseley, K. F.; Sellmeyer, D. E.] Johns Hopkins Sch Med, Div Endocrinol Diabet & Metab, Baltimore, MD USA. [Chia, C. W.; Simonsick, E. M.; Egan, J. M.; Ferrucci, L.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Moseley, K. F.] Johns Hopkins Bayview Med Ctr, Div Endocrinol Diabet & Metab, Baltimore, MD 21224 USA. RP Moseley, KF (reprint author), Johns Hopkins Bayview Med Ctr, Div Endocrinol Diabet & Metab, Mason Lord Ctr Tower,Suite 4300,5200 Eastern Ave, Baltimore, MD 21224 USA. EM kmosele4@jhmi.edu FU Intramural Research Program of the National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases [K23DK093720]; Legato Research Scholar Awards in Gender-Specific Medicine; Foundation for Gender-Specific Medicine, Inc.; National Institute on Aging FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging, and the National Institute of Diabetes and Digestive and Kidney Diseases, K23DK093720. It was also supported by the Legato Research Scholar Awards in Gender-Specific Medicine, Foundation for Gender-Specific Medicine, Inc. NR 38 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAY PY 2015 VL 26 IS 5 BP 1555 EP 1562 DI 10.1007/s00198-015-3027-z PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CF9RP UT WOS:000352904000011 PM 25619633 ER PT J AU Singewald, N Schmuckermair, C Whittle, N Holmes, A Ressler, KJ AF Singewald, N. Schmuckermair, C. Whittle, N. Holmes, A. Ressler, K. J. TI Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE Fear extinction; Exposure therapy; Augmented relearning; Reconsolidation; Drug development; Cognitive enhancer ID POSTTRAUMATIC-STRESS-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; FIBROBLAST-GROWTH-FACTOR; MEDIAL PREFRONTAL CORTEX; RANDOMIZED CONTROLLED-TRIAL; D-CYCLOSERINE AUGMENTATION; ACTIVATED PROTEIN-KINASE; PLACEBO-CONTROLLED TRIAL; RECEPTOR MESSENGER-RNA; GATED CALCIUM-CHANNELS AB Pathological fear and anxiety are highly debilitating and, despite considerable advances in psychotherapy and pharmacotherapy they remain insufficiently treated in many patients with PTSD, phobias, panic and other anxiety disorders. Increasing preclinical and clinical evidence indicates that pharmacological treatments including cognitive enhancers, when given as adjuncts to psychotherapeutic approaches [cognitive behavioral therapy including extinction-based exposure therapy] enhance treatment efficacy, while using anxiolytics such as benzodiazepines as adjuncts can undermine long-term treatment success. The purpose of this review is to outline the literature showing how pharmacological interventions targeting neurotransmitter systems including serotonin, dopamine, noradrenaline, histamine, glutamate, GABA, cannabinoids, neuropeptides (oxytocin, neuropeptides Y and S, opioids) and other targets (neurotrophins BDNF and FGF2, glucocorticoids, L-type-calcium channels, epigenetic modifications) as well as their downstream signaling pathways, can augment fear extinction and strengthen extinction memory persistently in preclinical models. Particularly promising approaches are discussed in regard to their effects on specific aspects of fear extinction namely, acquisition, consolidation and retrieval, including long-term protection from return of fear (relapse) phenomena like spontaneous recovery, reinstatement and renewal of fear. We also highlight the promising translational value of the preclinial research and the clinical potential of targeting certain neurochemical systems with, for example D-cycloserine, yohimbine, cortisol, and L-DOPA. The current body of research reveals important new insights into the neurobiology and neurochemistry of fear extinction and holds significant promise for pharmacologically-augmented psychotherapy as an improved approach to treat trauma and anxiety-related disorders in a more efficient and persistent way promoting enhanced symptom remission and recovery. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. C1 [Singewald, N.; Schmuckermair, C.; Whittle, N.] Univ Innsbruck, Inst Pharm, Dept Pharmacol & Toxicol, A-6020 Innsbruck, Austria. [Singewald, N.; Schmuckermair, C.; Whittle, N.] Univ Innsbruck, CMBI, A-6020 Innsbruck, Austria. [Holmes, A.] NIAAA, Lab Behav & Genom Neurosci, NIH, Bethesda, MD USA. [Ressler, K. J.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. RP Singewald, N (reprint author), Univ Innsbruck, Ctr Mol Biosci Innsbruck, Dept Pharmacol & Toxicol, Innrain 80-82, A-6020 Innsbruck, Austria. EM nicolas.singewald@uibk.ac.at OI Ressler, Kerry/0000-0002-5158-1103 FU Austrian Science Fund [FWF] [SFB F4410, P25375-B24] FX We acknowledge the Austrian Science Fund [FWF grant numbers SFB F4410 and P25375-B24] for funding our research related to this review (NS). NR 567 TC 45 Z9 46 U1 22 U2 83 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD MAY PY 2015 VL 149 BP 150 EP 190 DI 10.1016/j.pharmthera.2014.12.004 PG 41 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CG1BS UT WOS:000353008600004 PM 25550231 ER PT J AU Bruce, N Dherani, M Liu, R Hosgood, HD Sapkota, A Smith, KR Straif, K Lan, Q Pope, D AF Bruce, Nigel Dherani, Mukesh Liu, Rui Hosgood, H. Dean, III Sapkota, Amir Smith, Kirk R. Straif, Kurt Lan, Qing Pope, Daniel TI Does household use of biomass fuel cause lung cancer? A systematic review and evaluation of the evidence for the GBD 2010 study SO THORAX LA English DT Article ID INDOOR AIR-POLLUTION; SMOKE PARTICLE EXTRACTS; RISK-FACTORS; GLOBAL BURDEN; SOLID FUELS; WOMEN; METAANALYSIS; EXPOSURE; DISEASE; INDIA AB Background Around 2.4 billion people use traditional biomass fuels for household cooking or heating. In 2006, the International Agency for Research on Cancer (IARC) concluded emissions from household coal combustion are a Group 1 carcinogen, while those from biomass were categorised as 2A due to epidemiologic limitations. This review updates the epidemiologic evidence and provides risk estimates for the 2010 Global Burden of Disease study. Methods Searches were conducted of 10 databases to July 2012 for studies of clinically diagnosed or pathologically confirmed lung cancer associated with household biomass use for cooking and/or heating. Findings Fourteen eligible studies of biomass cooking or heating were identified: 13 had independent estimates (12 cooking only), all were case-control designs and provided 8221 cases and 11 342 controls. The ORs for lung cancer risk with biomass for cooking and/or heating were OR 1.17 (95% CI 1.01 to 1.37) overall, and 1.15 (95% CI 0.97 to 1.37) for cooking only. Publication bias was not detected, but more than half the studies did not explicitly describe a clean reference category. Sensitivity analyses restricted to studies with adequate adjustment and a clean reference category found ORs of 1.21 (95% CI 1.05 to 1.39) for men (two reports, compiling five studies) and 1.95 (95% CI 1.16 to 3.27) for women (five reports, compiling eight studies). Exposure-response evidence was seen for men, and higher risk for women in developing compared with developed countries, consistent with higher exposures in the former. Conclusions There is now stronger evidence for biomass fuel use causing lung cancer, but future studies need better exposure assessment to strengthen exposure-response evidence. C1 [Bruce, Nigel; Dherani, Mukesh; Pope, Daniel] Univ Liverpool, Dept Publ Hlth & Policy, Liverpool L69 3GB, Merseyside, England. [Liu, Rui; Smith, Kirk R.] Univ Calif Berkeley, Sch Publ Hlth, Environm Hlth Sci, Berkeley, CA 94720 USA. [Hosgood, H. Dean, III; Lan, Qing] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Hosgood, H. Dean, III] Albert Einstein Coll Med, Div Epidemiol, Bronx, NY 10467 USA. [Sapkota, Amir] Univ Maryland, Maryland Inst Appl Environm Hlth, Sch Publ Hlth, College Pk, MD 20742 USA. [Straif, Kurt] Int Agcy Res Canc, F-69372 Lyon, France. RP Bruce, N (reprint author), Univ Liverpool, Dept Publ Hlth & Policy, Whelan Bldg, Liverpool L69 3GB, Merseyside, England. EM ngb@liv.ac.uk RI Sapkota, Amir/A-5968-2011 FU Bill and Melinda Gates Foundation FX A grant from the Bill and Melinda Gates Foundation partially supported the collaboration between some of the authors of this review. NR 33 TC 5 Z9 6 U1 4 U2 10 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 EI 1468-3296 J9 THORAX JI Thorax PD MAY PY 2015 VL 70 IS 5 BP 433 EP 441 DI 10.1136/thoraxjnl-2014-206625 PG 9 WC Respiratory System SC Respiratory System GA CF8XY UT WOS:000352846600008 PM 25758120 ER PT J AU Dickherber, A Morris, SA Grodzinski, P AF Dickherber, Anthony Morris, Stephanie A. Grodzinski, Piotr TI NCI investment in nanotechnology: achievements and challenges for the future SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY LA English DT Review ID IN-VIVO; CANCER NANOTECHNOLOGY; PRECISION MEDICINE; QUANTUM DOTS; DELIVERY; NANOPARTICLE; CELLS; NANOMEDICINE; ONCOLOGY; TUMORS AB Nanotechnology offers an exceptional and unique opportunity for developing a new generation of tools addressing persistent challenges to progress in cancer research and clinical care. The National Cancer Institute (NCI) recognizes this potential, which is why it invests roughly $150 M per year in nanobiotechnology training, research and development. By exploiting the various capacities of nanomaterials, the range of nanoscale vectors and probes potentially available suggests much is possible for precisely investigating, manipulating, and targeting the mechanisms of cancer across the full spectrum of research and clinical care. NCI has played a key role among federal R&D agencies in recognizing early the value of nanobiotechnology in medicine and committing to its development as well as providing training support for new investigators in the field. These investments have allowed many in the research community to pursue breakthrough capabilities that have already yielded broad benefits. Presented here is an overview of how NCI has made these investments with some consideration of how it will continue to work with this research community to pursue paradigm-changing innovations that offer relief from the burdens of cancer.Published 2014. This article is a U.S. Government work and is in the public domain in the USA. C1 [Dickherber, Anthony] NCI, Off Director, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA. [Morris, Stephanie A.; Grodzinski, Piotr] NCI, Office Canc Nanotechnol Res, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA. RP Dickherber, A (reprint author), NCI, Off Director, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA. EM anthony.dickherber@nih.gov FU NIH FX Data obtained using NIH RePORTer (http://projectreporter.nih.gov) for all SBIR/STTR contract and grant awards between FY09-13. NR 72 TC 3 Z9 3 U1 4 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-5116 EI 1939-0041 J9 WIRES NANOMED NANOBI JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol. PD MAY-JUN PY 2015 VL 7 IS 3 BP 251 EP 265 DI 10.1002/wnan.1318 PG 15 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA CF8LK UT WOS:000352811000001 PM 25429991 ER PT J AU Sigurdardottir, EE Turesson, I Lund, SH Lindqvist, EK Mailankody, S Korde, N Bjorkholm, M Landgren, O Kristinsson, SY AF Sigurdardottir, Elin Edda Turesson, Ingemar Lund, Sigrun Helga Lindqvist, Ebba K. Mailankody, Sham Korde, Neha Bjorkholm, Magnus Landgren, Ola Kristinsson, Sigurdur Y. TI The Role of Diagnosis and Clinical Follow-up of Monoclonal Gammopathy of Undetermined Significance on Survival in Multiple Myeloma SO JAMA ONCOLOGY LA English DT Article ID SIGNIFICANCE MGUS; WORKING GROUP; LONG-TERM; RISK; POPULATION; SWEDEN; MALIGNANCIES; PROGRESSION; PREVALENCE; VALIDATION AB IMPORTANCE Multiple myeloma (MM) is consistently preceded by the precursor state, monoclonal gammopathy of undetermined significance (MGUS). The average annual risk of progression from MGUS to multiple myeloma is 0.5% to 1.0%. Current guidelines suggest life-long clinical follow-up of individuals diagnosed as having MGUS depending on risk stratification. The impact of diagnosing and conducting clinical follow-up of MGUS on MM survival is unclear. OBJECTIVE To estimate the impact of prior knowledge of MGUS diagnosis and comorbidities on MM survival. DESIGN, SETTING, AND PARTICIPANTS We conducted a population-based study including all patients with MM(MM patients) diagnosed in Sweden (n = 14 798) from 1976 to 2005 (with follow-up until 2007); 394 (2.7%) had previously been diagnosed as having MGUS. Information on comorbidities was gathered for all patients. We calculated survival rates from the time of MM diagnosis, comparing patients with vs those without prior knowledge of MGUS. Using Cox proportional hazards models, we calculated hazard ratios (HRs) and 95% CIs for risk factors for death. chi(2) Tests were used to evaluate differences in comorbidities. EXPOSURES Prior knowledge of MGUS among MM patients. In a subanalysis, monoclonal (M)-protein concentration and type were used as exposure. MAIN OUTCOMES AND MEASURES Risk of death and comorbidities. RESULTS Patients with MM with prior knowledge of MGUS had significantly (HR, 0.86; 95% CI, 0.77-0.96; P<.01) better overall survival (median survival, 2.8 years) than MM patients without prior knowledge of MGUS (median survival, 2.1 years), although MM patients with (vs without) prior knowledge of MGUS had more comorbidities (P<.001). Among MM patients with prior knowledge of MGUS, low M-protein concentration (<0.5 g/dL) at MGUS diagnosis was associated with poorer MM survival (HR, 1.86; 95% CI, 1.13-3.04; P=.01). CONCLUSIONS AND RELEVANCE Patients with MM with prior knowledge of MGUS had better MM survival, suggesting that earlier treatment of MM leads to better survival. The observation that a low M-protein concentration at MGUS diagnosis was associated with poorer MM survival may reflect less frequent clinical follow-up. Our observations stress the importance of clinical follow-up in patients with MGUS, regardless of risk stratification. C1 [Sigurdardottir, Elin Edda; Lund, Sigrun Helga; Kristinsson, Sigurdur Y.] Univ Iceland, Fac Med, Stapi 5, Reykjavik 101, Iceland. [Turesson, Ingemar] Skane Univ Hosp, Dept Hematol & Coagulat Disorders, Malmo, Sweden. [Lindqvist, Ebba K.; Bjorkholm, Magnus; Kristinsson, Sigurdur Y.] Karolinska Univ Hosp, Div Hematol, Dept Med, Stockholm, Sweden. [Lindqvist, Ebba K.; Bjorkholm, Magnus; Kristinsson, Sigurdur Y.] Karolinska Inst, Stockholm, Sweden. [Mailankody, Sham; Korde, Neha] NCI, Multiple Myeloma Sect, Lymphoid Malignancies Branch, Bethesda, MD 20892 USA. [Landgren, Ola] Mem Sloan Kettering Canc Ctr, Myeloma Serv, New York, NY 10021 USA. RP Kristinsson, SY (reprint author), Univ Iceland, Fac Med, Stapi 5, Reykjavik 101, Iceland. EM sigyngvi@hi.is RI Kristinsson, Sigurdur /M-2910-2015; Lund, Sigrun Helga/K-9144-2015; OI Kristinsson, Sigurdur /0000-0002-4964-7476; Lund, Sigrun Helga/0000-0002-3806-2296; Lindqvist, Ebba K/0000-0001-7662-1338 FU Swedish Cancer Society; Karolinska Institutet Foundations; Marie-Curie CIG; University of Iceland Research Fund; Icelandic Centre for Research (RANNIS); Landspitali University Hospital Research Fund FX This research was supported by grants from the Swedish Cancer Society, the Karolinska Institutet Foundations, Marie-Curie CIG, the University of Iceland Research Fund, Icelandic Centre for Research (RANNIS), and Landspitali University Hospital Research Fund. NR 26 TC 13 Z9 13 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA EI 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD MAY PY 2015 VL 1 IS 2 BP 168 EP 174 DI 10.1001/jamaoncol.2015.23 PG 7 WC Oncology SC Oncology GA DW5FK UT WOS:000383668400008 PM 26181017 ER PT J AU Adkins, E Wang, XL Sproule, T Christianson, G Park, G Lane-Reticker, SK Carter, G Morse, H Roopenian, D AF Adkins, Elisabeth Wang, Xulong Sproule, Thomas Christianson, Gregory Park, Giljun Lane-Reticker, Sarah Kate Carter, Gregory Morse, Herbert Roopenian, Derry TI An IL21 reporter mouse reveals a novel population of T-FH precursors in young mice. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Adkins, Elisabeth; Wang, Xulong; Sproule, Thomas; Christianson, Gregory; Park, Giljun; Lane-Reticker, Sarah Kate; Carter, Gregory; Roopenian, Derry] Jackson Lab, Bar Harbor, ME 04609 USA. [Adkins, Elisabeth; Carter, Gregory; Roopenian, Derry] Tufts Univ, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. [Morse, Herbert] NIAID, Virol & Cellular Immunol, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA LYM8P.630 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503270 ER PT J AU Alam, M Gaida, M Bergmann, F Lasitschka, F Giese, T Giese, N Hackert, T Hinz, U Hossain, S Kozlov, S Ashwell, J AF Alam, Muhammad Gaida, Matthias Bergmann, Frank Lasitschka, Felix Giese, Thomas Giese, Nathalia Hackert, Thilo Hinz, Ulf Hossain, S. Kozlov, Serguei Ashwell, Jonathan TI Selective inhibition of the T cell p38 alternative activation pathway and pancreatic cancer SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Alam, Muhammad; Ashwell, Jonathan] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. [Gaida, Matthias; Bergmann, Frank; Lasitschka, Felix] Univ Heidelberg Hosp, Inst Pathol, Heidelberg, Germany. [Kozlov, Serguei] NCI, Canc & Dev Biol, NIH, Frederick, MD 21701 USA. [Hossain, S.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Giese, Thomas] Heidelberg Univ, Inst Immunol, Heidelberg, Germany. [Giese, Nathalia; Hackert, Thilo; Hinz, Ulf] Heidelberg Univ, Dept Surg, Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA TUM3P.1046 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502163 ER PT J AU Azzam, K Madenspacher, J Lai, LH Gowdy, K Cain, D Clayton, N Cunningham, W Janardhan, K Taylor, G Fessler, M AF Azzam, Kathleen Madenspacher, Jennifer Lai, Lihua Gowdy, Kimberly Cain, Derek Clayton, Natasha Cunningham, Willie Janardhan, Kyathanahalli Taylor, Gregory Fessler, Michael TI A novel role for Irgm1 in immune homeostasis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Azzam, Kathleen; Madenspacher, Jennifer; Fessler, Michael] NIEHS, LRB, NIH, Durham, NC USA. [Lai, Lihua] Zhejiang Univ, Sch Med, Hangzhou, Zhejiang, Peoples R China. [Gowdy, Kimberly] ECU, Greenville, NC USA. [Cain, Derek; Clayton, Natasha; Cunningham, Willie; Janardhan, Kyathanahalli] NIEHS, Durham, NC USA. [Taylor, Gregory] Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA MUC1P.906 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503288 ER PT J AU Bayik, D Wang, J Gursel, I Klinman, D AF Bayik, Defne Wang, Jing Gursel, Ihsan Klinman, Dennis TI Defined combinations of cytokines plus survival factors drive the differentiation of human monocytic myeloid derived suppressor cells into M1-or M2-like macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Gursel, Ihsan] Bilkent Univ, Ankara, Turkey. [Bayik, Defne; Wang, Jing; Klinman, Dennis] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA TUM6P.969 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503120 ER PT J AU Bhattacharya, P Dey, R Dagur, P Kruhlak, M Debrabant, A Okeeffe, NI McCoy, J Nakhasi, H AF Bhattacharya, Parna Dey, Ranadhir Dagur, Pradeep Kruhlak, Michael Debrabant, Alain Okeeffe, Nevien Ismail McCoy, John Nakhasi, Hira TI Genetically modified live attenuated L. donovani parasite induces classical activation of macrophages (M1 phenotype) leading to generation of Th1 response in BALB/c mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Dagur, Pradeep; McCoy, John] NHLBI, NIH, Bethesda, MD 20892 USA. [Kruhlak, Michael] NCI, NIH, Bethesda, MD 20892 USA. [Bhattacharya, Parna; Dey, Ranadhir; Debrabant, Alain; Okeeffe, Nevien Ismail; Nakhasi, Hira] US FDA, DETTD, CBER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VAC4P.1102 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504121 ER PT J AU Bolland, S Voynova, E Skinner, J Scott, B Qi, CF AF Bolland, Silvia Voynova, Elisaveta Skinner, Jeffrey Scott, Bethany Qi, Chen-Feng TI Induction of autoimmune disease by adoptive transfer of an atypical NK cell subset SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Bolland, Silvia; Voynova, Elisaveta; Skinner, Jeffrey; Scott, Bethany; Qi, Chen-Feng] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA BA7P.147 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501264 ER PT J AU Caspi, R Mattapallil, M Rigden, R Zarate-Blades, C Silver, P Luger, D Chan, CC AF Caspi, Rachel Mattapallil, Mary Rigden, Rachael Zarate-Blades, Carlos Silver, Phyllis Luger, Dror Chan, Chi Chao TI Neuroprotective effects of IL-22 during CNS inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Caspi, Rachel; Mattapallil, Mary; Rigden, Rachael; Zarate-Blades, Carlos; Silver, Phyllis; Luger, Dror; Chan, Chi Chao] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA CCR4P.203 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501035 ER PT J AU Chen, GB Subedi, K Mi, J Shi, A Weng, NP AF Chen, Guobing Subedi, Kalpana Mi, Jenny Shi, Alvin Weng, Nan-Ping TI Histone methyltransferase Ezh2 is critical for activation-induced CD8 T cell proliferation and survival SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Chen, Guobing; Subedi, Kalpana; Mi, Jenny; Shi, Alvin; Weng, Nan-Ping] NIA, NIH, Baltimore, MD 21224 USA. RI Chen, Guobing/D-9572-2012 OI Chen, Guobing/0000-0002-2401-6168 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA LYM7P.615 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502229 ER PT J AU Chen, P Denniston, A Hannes, S Tucker, W Wei, L Liu, BY Hirani, S Li, ZY Lee, R Sen, H Nussenblatt, R AF Chen, Ping Denniston, Alastair Hannes, Susan Tucker, William Wei, Lai Liu, Baoying Hirani, Sima Li, Zhiyu Lee, Richard Sen, H. Nussenblatt, Robert TI Myeloid dendritic cells with elevated CD1c expression in non-infectious uveitis patients exhibited mature phenotype through the regulation of TNFa-p38 MAPK pathway SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Chen, Ping; Hannes, Susan; Tucker, William; Wei, Lai; Liu, Baoying; Hirani, Sima; Li, Zhiyu; Sen, H.; Nussenblatt, Robert] NIH, Bldg 10, Bethesda, MD 20892 USA. [Denniston, Alastair] Queen Elizabeth Hosp Birmingham, Edgbaston, England. [Lee, Richard] Univ Bristol, Bristol, Avon, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HUM1P.273 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500321 ER PT J AU Chiang, J Hodes, R AF Chiang, Jeffrey Hodes, Richard TI T cell development is regulated by the coordinated function of two Lck promoters SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Chiang, Jeffrey] NCI, EIB, NIH, Bethesda, MD 20892 USA. [Hodes, Richard] NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA IRM7P.701 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504330 ER PT J AU Cunningham, M Myers, J Cooper, L Kem, D Stavrakis, S Shevach, E Fairweather, D Stoner, J Cox, C AF Cunningham, Madeleine Myers, Jennifer Cooper, Leslie Kem, David Stavrakis, Stavros Shevach, Ethan Fairweather, DeLisa Stoner, Julie Cox, Carol TI Cardiac myosin and the Th17 immunophenotype in human autoimmune myocarditis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Cunningham, Madeleine; Myers, Jennifer; Kem, David; Stavrakis, Stavros; Stoner, Julie; Cox, Carol] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Cooper, Leslie] Mayo Clin, Rochester, MN USA. [Shevach, Ethan] Natl Inst Allergy & Immunol, Bethesda, MD USA. [Fairweather, DeLisa] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HUM1P.252 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500302 ER PT J AU Dileepan, T Linehan, J Cleary, P Jenkins, M AF Dileepan, Thamotharampillai Linehan, Jonathan Cleary, P. Jenkins, Marc TI Robust Th17 response to intranasal group A streptococcal infection requires IL-6 produced by CD301b(+)CD11b(+)CD103(-) migratory dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Dileepan, Thamotharampillai; Cleary, P.; Jenkins, Marc] Univ Minnesota, Minneapolis, MN USA. [Linehan, Jonathan] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA MUC2P.937 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504052 ER PT J AU Felber, B Bergamaschi, C Ng, SM Chen, S Bear, J Alicea, C Beach, RK Chertova, E Sowder, R Pavlakis, G AF Felber, Barbara Bergamaschi, Cristina Ng, Sin Man Chen, Stephanie Bear, Jenifer Alicea, Candido Beach, Rachel Kelly Chertova, Elena Sowder, Raymond Pavlakis, George TI Heterodimeric IL-15 regulates the balance of effector and regulatory cells, promoting anti-cancer tumor effects SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Felber, Barbara; Bergamaschi, Cristina; Ng, Sin Man; Chen, Stephanie; Bear, Jenifer; Alicea, Candido; Beach, Rachel Kelly; Pavlakis, George] NCI, Ctr Canc Res, Frederick, MD 21701 USA. [Chertova, Elena; Sowder, Raymond] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA CCR4P.213 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501030 ER PT J AU Golding, A Darko, S Wylie, W Douek, D Shevach, E AF Golding, Amit Darko, Samuel Wylie, William Douek, Daniel Shevach, Ethan TI Deep sequencing of the TCRB repertoire of human Foxp3(+) and Foxp3(-) T cells demonstrates that they are completely distinct and non-overlapping SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Golding, Amit] Univ Maryland, Dept Rheumatol, Baltimore, MD 21201 USA. [Golding, Amit] VA Maryland Hlth Care Syst, Med Res, Baltimore, MD USA. [Darko, Samuel; Wylie, William; Douek, Daniel] NIAID, VRC, NIH, Bethesda, MD 20892 USA. [Shevach, Ethan] NIAID, LI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA LYM8P.638 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503275 ER PT J AU Gomez-Rodriguez, J Meylan, F Handon, R Hayes, E Siegel, R Schwartzberg, P AF Gomez-Rodriguez, Julio Meylan, Francoise Handon, Robin Hayes, Erika Siegel, Richard Schwartzberg, Pamela TI The Tec family kinase Itk is required for Th9 cell differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Gomez-Rodriguez, Julio; Meylan, Francoise; Handon, Robin; Hayes, Erika; Siegel, Richard; Schwartzberg, Pamela] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA LYM8P.642 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503271 ER PT J AU Gowdy, K Madenspacher, J Thomas, S Nakano, H Cook, D Fessler, M AF Gowdy, Kymberly Madenspacher, Jennifer Thomas, Seddon Nakano, Hideki Cook, Donald Fessler, Michael TI Novel role for scavenger receptor B-I in neutrophilic asthma SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Madenspacher, Jennifer; Thomas, Seddon; Nakano, Hideki; Cook, Donald; Fessler, Michael] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Gowdy, Kymberly] East Carolina Univ, Pharmacol & Toxicol, Greenville, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA IRC10P.419 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503248 ER PT J AU Green, S Smith, M Hasley, R Stephany, D Harned, A Nagashima, K Imamichi, T Qin, J Rupert, A Ober, A Lane, H Catalfamo, M AF Green, Samantha Smith, Mindy Hasley, Rebecca Stephany, David Harned, Adam Nagashima, Kunio Imamichi, Tomozumi Qin, Jing Rupert, Adam Ober, Alexander Lane, H. Catalfamo, Marta TI Increased activated platelet-T cell conjugates in patients with HIV infection: relationship between coagulation/inflammation and T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Green, Samantha; Smith, Mindy; Hasley, Rebecca; Ober, Alexander; Lane, H.; Catalfamo, Marta] NIAID, CMRS LIR, NIH, Bethesda, MD 20892 USA. [Stephany, David] NIAID, NIH, Bethesda, MD 20892 USA. [Harned, Adam; Nagashima, Kunio] Leidos Biomed Res Inc, Electron Microscopy Lab, Canc Res Technol Program, Frederick, MD USA. [Imamichi, Tomozumi] Leidos Biomed Res Inc, Collaborat Clin Res Branch, Frederick, MD USA. [Qin, Jing] NIAID, DCR BRB, NIH, Rockville, MD USA. [Rupert, Adam] Leidos Biomed Res Inc, AIDS Monitoring Labs, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504064 ER PT J AU Gros, A Tran, E Pasetto, A Parkhurst, MR Prickett, T Gartner, J Yu, ZY Wunderlich, J Robbins, P Yang, J Rosenberg, S AF Gros, Alena Tran, Eric Pasetto, Anna Parkhurst, Maria R. Prickett, Todd Gartner, Jared Yu, Zhiya Wunderlich, John Robbins, Paul Yang, James Rosenberg, Steve TI PD-1 expression on peripheral blood lymphocytes enables direct enrichment of mutation-specific lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Gros, Alena; Tran, Eric; Pasetto, Anna; Parkhurst, Maria R.; Prickett, Todd; Gartner, Jared; Yu, Zhiya; Wunderlich, John; Robbins, Paul; Yang, James; Rosenberg, Steve] NCI, Surg Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VAC12P1117 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501021 ER PT J AU Guenther, G Telford, W AF Guenther, Garret Telford, William TI Comparison of flow cytometers using the side population technique to identify stem cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Guenther, Garret] ACEA Biosci, San Diego, CA USA. [Telford, William] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA TECH2P.900 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504164 ER PT J AU Gurusamy, D Shoe, J Hocker, J Hurwitz, A AF Gurusamy, Devikala Shoe, Jennifer Hocker, James Hurwitz, Arthur TI A role for IL-13 in the progression of prostate tumors SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Gurusamy, Devikala; Shoe, Jennifer; Hocker, James; Hurwitz, Arthur] NCI, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504297 ER PT J AU Hajduczki, A Bundoc, V Berger, E AF Hajduczki, Agnes Bundoc, Virgilio Berger, Edward TI Developing soluble mimetics of the chemokine receptor CCR5 for the study of HIV Env/receptor interactions SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Hajduczki, Agnes; Bundoc, Virgilio; Berger, Edward] NIAID, Lab Viral Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA CCR6P.216 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502025 ER PT J AU Hart, G Gordon, E Waisberg, M Tran, T Akkaya, M Skinner, J Zinocker, S Pena, M Yazew, T Qi, CF Miller, L Pierce, S AF Hart, Geoffrey Gordon, Emile Waisberg, Michael Tran, Tuan Akkaya, Munir Skinner, Jeffrey Zinocker, Severin Pena, Mirna Yazew, Takele Qi, Chenfeng Miller, Louis Pierce, Susan TI Inhibiting the mammalian target of rapamycin as an adjunctive therapy for cerebral malaria SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Hart, Geoffrey; Gordon, Emile; Waisberg, Michael; Tran, Tuan; Akkaya, Munir; Skinner, Jeffrey; Zinocker, Severin; Pena, Mirna; Yazew, Takele; Qi, Chenfeng; Miller, Louis; Pierce, Susan] NIAID, NIH, Rockville, MD USA. [Gordon, Emile] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Waisberg, Michael] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA MPF7P.714 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503045 ER PT J AU Hayes, E Villarreal, S Ferdinand, J Engel, O Meylan, F Siegel, R AF Hayes, Erika Villarreal, Sarah Ferdinand, John Engel, Odile Meylan, Francoise Siegel, Richard TI The TNF-family cytokine receptor death-receptor 3 (TNFRSF25) is required for nephritis but not systemic autoimmunity in the Ipr murine model of lupus SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Hayes, Erika; Villarreal, Sarah; Ferdinand, John; Engel, Odile; Meylan, Francoise; Siegel, Richard] NIAMS, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA CCR5P.209 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501055 ER PT J AU Hessell, A Sacha, J Kahl, C Graham, B Mascola, J Haigwood, N AF Hessell, Ann Sacha, Jonah Kahl, Christoph Graham, Barney Mascola, John Haigwood, Nancy TI Post-exposure treatment with neutralizing monoclonal antibodies prevents SHIV infection in infant rhesus macaques and limits establishment of latent viral reservoirs SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Hessell, Ann; Sacha, Jonah; Kahl, Christoph; Haigwood, Nancy] Oregon Hlth & Sci Univ, Beaverton, OR USA. [Graham, Barney; Mascola, John] NIAID, Vaccine Res Ctr, NIH, Bethesday, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500212 ER PT J AU Jain, S Adkins, E Christianson, G Sproule, T Roopenian, D Morse, H AF Jain, Shweta Adkins, Elisabeth Christianson, Gregory Sproule, Thomas Roopenian, Derry Morse, Herbert TI Interleukin 6 (IL6) is an important upstream contributor towards the progression of SLE-like disease in BXSB.Yaa mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Jain, Shweta; Morse, Herbert] NIAID, NIH, Rockville, MD USA. [Adkins, Elisabeth; Christianson, Gregory; Sproule, Thomas; Roopenian, Derry] Jackson Labs, Bar Harbor, ME USA. [Adkins, Elisabeth] Tufts Univ, Sackler Sch Grad Biomed Sci, Genet Program, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA BA11P.134 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504141 ER PT J AU Jain, S Trivett, M Ayala, V Coren, L Barsov, E Ohlen, C Ott, D AF Jain, Sumiti Trivett, Matthew Ayala, Victor Coren, Lori Barsov, Eugene Ohlen, Claes Ott, David TI SIV-specific rhesus CD4 T cells expressing African green monkey TRIM5 alpha exhibit prolonged persistence and enhanced antiviral function. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Jain, Sumiti; Trivett, Matthew; Ayala, Victor; Coren, Lori; Barsov, Eugene; Ohlen, Claes; Ott, David] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VIR1P.1153 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500033 ER PT J AU Janosko, K Cohen, M Josleyn, N Zhang, TF Cong, Y Jahrling, P Johnson, R AF Janosko, Krisztina Cohen, Melanie Josleyn, Nicole Zhang, Tengfei Cong, Yu Jahrling, Peter Johnson, Reed TI Pro-inflammatory cytokine production by activated monocytes and macrophages in response to cowpox virus infection in cynomologus macaques SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Janosko, Krisztina; Cohen, Melanie; Josleyn, Nicole; Zhang, Tengfei; Cong, Yu; Jahrling, Peter] NIAID, Integrated Res Facil, Frederick, MD USA. [Jahrling, Peter; Johnson, Reed] NIAID, Emerging Viral Pathogens Sect, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VIR9P.1144 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502002 ER PT J AU Jeon, H Williams, J Hodes, R AF Jeon, Hyein Williams, Joy Hodes, Richard TI Cell types and cell signals important for normal thymic medullary epithelial cell development SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Jeon, Hyein; Williams, Joy] NCI, NIH, Bethesda, MD 20892 USA. [Hodes, Richard] NIH, NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HEM7P.231 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504211 ER PT J AU Josleyn, N Yellayi, S Martinez, M Janosko, K Adams, R Burdette, T Cohen, M Zhang, TF Jahrling, P Johnson, R AF Josleyn, Nicole Yellayi, Srikanth Martinez, Mark Janosko, Krisztina Adams, Ricky Burdette, Tracey Cohen, Melanie Zhang, Tengfei Jahrling, Peter Johnson, Reed TI Evaluation of bone marrow in cowpox virus infection in cynomolgus macaques SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Josleyn, Nicole; Yellayi, Srikanth; Martinez, Mark; Janosko, Krisztina; Adams, Ricky; Burdette, Tracey; Cohen, Melanie; Zhang, Tengfei; Jahrling, Peter] NIAID, Integrated Res Facil, NIH, Frederick, MD USA. [Jahrling, Peter; Johnson, Reed] NIAID, Emerging Viral Pathogens Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VIR1P.1127 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500041 ER PT J AU Kamphorst, A Watanabe, M Araki, K Rasheed, MAU Davis, C Yang, S Konieczny, B Hodes, R Ahmed, R AF Kamphorst, Alice Watanabe, Masashi Araki, Koichi Rasheed, Mohammed Ata Ur Davis, Carl Yang, Shu Konieczny, Bogumila Hodes, Richard Ahmed, Rafi TI Differential role of B7 co-stimulation on B cells and dendritic cells for Th1 and Tfh differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Kamphorst, Alice; Araki, Koichi; Rasheed, Mohammed Ata Ur; Davis, Carl; Yang, Shu; Konieczny, Bogumila; Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Microbiol & Immunol, Atlanta, GA USA. [Watanabe, Masashi; Hodes, Richard] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA LYM8P.631 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503259 ER PT J AU Kang, JG Sung, HJ Amar, M Remaley, A Springer, D Kwon, J Chen, JC Wang, PY Hwang, P AF Kang, Ju-Gyeong Sung, Ho Joong Amar, Marcelo Remaley, Alan Springer, Danielle Kwon, Jaeyul Chen, Jichun Wang, Pingyuan Hwang, Paul TI Low ambient oxygen prevents atherosclerosis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Kang, Ju-Gyeong; Amar, Marcelo; Remaley, Alan; Springer, Danielle; Chen, Jichun; Wang, Pingyuan; Hwang, Paul] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Sung, Ho Joong] Eulji Univ, Gyeonggi Do, South Korea. [Kwon, Jaeyul] Chungnam Natl Univ, Daejeon, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HUM1P.254 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500317 ER PT J AU Karauzum, H Datta, S AF Karauzum, Hatice Datta, Sandip TI Immunization with superantigen-derived oligopeptides protect against S-aureus bacteremia SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Datta, Sandip] NIAID, NIH, Bethesda, MD 20892 USA. [Karauzum, Hatice] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VAC8P.1058 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503175 ER PT J AU Kenyon, E Nayak, D Moseman, E McGavern, D AF Kenyon, Elizabeth Nayak, Debasis Moseman, E. McGavern, Dorian TI Tetherin (BST-2) promotes control of a persistent infection by reducing viral spread and T cell exhaustion SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Kenyon, Elizabeth; Nayak, Debasis; Moseman, E.; McGavern, Dorian] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504055 ER PT J AU Khan, B Mukherjee, P Taylor, K Woods, T Winkler, C Peterson, K AF Khan, Burhan Mukherjee, Piyali Taylor, Katherine Woods, Tyson Winkler, Clayton Peterson, Karin TI The role of SARM1 in Toll-like receptor and viral-induced neuronal apoptosis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Khan, Burhan; Mukherjee, Piyali; Taylor, Katherine; Woods, Tyson; Winkler, Clayton; Peterson, Karin] NIAID, Persistent Viral Dis Lab, NIH, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA INM7P.347 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504224 ER PT J AU Kielczewski, J Horai, R Caspi, R AF Kielczewski, Jennifer Horai, Reiko Caspi, Rachel TI Retina-specific T cells provide neuroprotection in a mouse model of glaucoma SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Kielczewski, Jennifer; Horai, Reiko; Caspi, Rachel] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA BA6P.140 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500199 ER PT J AU Kim, HK Castro, E Voong, N Telford, W Gress, R AF Kim, Hye Kyung Castro, Ehydel Voong, Nga Telford, William Gress, Ronald TI Enhanced IL-7 responsiveness provides competitive advantage to recent thymic emigrants in peripheral T cell survival and homeostasis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Kim, Hye Kyung; Castro, Ehydel; Voong, Nga; Telford, William; Gress, Ronald] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA IRC8P.451 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504085 ER PT J AU Kimura, M Nakayama, T Singer, A AF Kimura, Motoko Nakayama, Toshinori Singer, Alfred TI Strong TCR signaling prolongs lineage uncertainty during MHC-1 specific positive selection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Kimura, Motoko; Nakayama, Toshinori] Chiba Univ, Dept Immunol, Chiba, Japan. [Singer, Alfred] NCI, NIH, Bethesda, MD 20892 USA. RI Nakayama, Toshinori/E-1067-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HEM8P.241 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502029 ER PT J AU Kiwanuka, K Lin, JX Leonard, W Ryan, J AF Kiwanuka, Kasalina Lin, Jian-Xin Leonard, Warren Ryan, John TI STAT5 tetramer formation is critical for mast cell function SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Kiwanuka, Kasalina; Ryan, John] Virginia Commonwealth Univ, Richmond, VA USA. [Lin, Jian-Xin; Leonard, Warren] NHLBI, NIH, Lab Mol Immunol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HYP4P.312 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502251 ER PT J AU Laky, K Evans, S Fowlkes, B AF Laky, Karen Evans, Sharron Fowlkes, B. TI Notch signaling regulates antigen sensitivity of naive CD4(+) T cells by tuning co-stimulation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Laky, Karen] NIH, Bethesda, MD 20892 USA. [Laky, Karen; Evans, Sharron; Fowlkes, B.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA LYM7P.613 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502231 ER PT J AU Lalani, A Luo, C Morse, H Xie, P AF Lalani, Almin Luo, Chang Morse, Herbert Xie, Ping TI Specific deletion of TRAF3 in myeloid cells leads to spontaneous inflammation and tumor development in mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Lalani, Almin; Luo, Chang; Xie, Ping] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ USA. [Morse, Herbert] NIAID, Immunopathol Lab, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA INC6P.304 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501326 ER PT J AU Le Saout, C Hasley, R Imamichi, H Tcheung, L Hu, ZH Smith, M Rupert, A Sneller, M Lane, H Catalfamo, M AF Le Saout, Cecile Hasley, Rebecca Imamichi, Hiromi Tcheung, Lueng Hu, Zonghui Smith, Mindy Rupert, Adam Sneller, Michael Lane, H. Catalfamo, Marta TI Role of IFN-alpha signaling in T cell pool dysregulation during chronic exposure to type-I IFN under lymphopenic conditions: impact on HIV pathogenesis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Le Saout, Cecile; Hasley, Rebecca; Imamichi, Hiromi; Tcheung, Lueng; Smith, Mindy; Sneller, Michael; Lane, H.; Catalfamo, Marta] NIAID, CMRS, LIR, Bethesda, MD 20892 USA. [Hu, Zonghui] NIAID, Biostat Res Branch, DCR, Bethesda, MD 20892 USA. [Rupert, Adam] SAIC Frederick Inc, AIDS Monitoring Labs, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VIR9P.1145 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501340 ER PT J AU Lowe, J Menendez, D Nguyen, TA Grim, S Resnick, M Fessler, M AF Lowe, Julie Menendez, Daniel Thuy-Ai Nguyen Grim, Sara Resnick, Michael Fessler, Michael TI p53 regulates expression of the early response gene tumor necrosis factor-alpha-induced protein 8 in macrophage SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Lowe, Julie; Menendez, Daniel; Thuy-Ai Nguyen; Grim, Sara; Resnick, Michael; Fessler, Michael] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA IRM6P.660 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501098 ER PT J AU Lu, W Zhang, Y Hambleton, S Lenardo, M AF Lu, Wei Zhang, Yu Hambleton, Sophie Lenardo, Michael TI Tripeptidyl peptidase II links intracellular amino acids homeostasis with immune response through glycolytic pathway SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Lu, Wei; Lenardo, Michael] NIAID, Immunol Lab, MDISS, Bethesda, MD 20892 USA. [Hambleton, Sophie] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Zhang, Yu] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA IRM9P.463 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502312 ER PT J AU Marrero, B Liu, Y Huang, Y De Jesus, AA Goldbach-Mansky, R AF Marrero, Bernadette Liu, Yin Huang, Yan De Jesus, Adriana Almeida Goldbach-Mansky, Raphaela TI Comparative studies connecting IFN dysregulation with pathway dysregulation in 2 autoinflammatory diseases, SAVI and CANDLE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Marrero, Bernadette; Liu, Yin; Huang, Yan; De Jesus, Adriana Almeida; Goldbach-Mansky, Raphaela] Natl Inst Arthrit Musculoskeletal & Skin, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HUM1P.274 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500313 ER PT J AU McBerry, C Sakai, S Kauffman, K Barber, D AF McBerry, Cortez Sakai, Shunsuke Kauffman, Keith Barber, Daniel TI Supraphysiological myeloid cell activation during mycobacterial immune reconstitution inflammatory syndrome SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [McBerry, Cortez; Sakai, Shunsuke; Kauffman, Keith; Barber, Daniel] NIAID, LPD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA IRC4P.456 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501283 ER PT J AU Mehta, G Sukumar, M McGavern, D Restifo, N AF Mehta, Gautam Sukumar, Madhuhasan McGavern, Dorian Restifo, Nicholas TI PD-1 blockade reverts motility arrest of transferred tumor-infiltrating CD8+T cells in adoptive cell transfer immunotherapy SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Mehta, Gautam] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. [Mehta, Gautam; Sukumar, Madhuhasan; Restifo, Nicholas] NCI, Surg Branch, Bethesda, MD 20892 USA. [McGavern, Dorian] NINDS, Viral Immunol & Intravital Imaging Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA TUM7P.1014 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504110 ER PT J AU Meylan, F Richard, A Tan, C Hawley, E Gomez-Rodriguez, J Goswami, R Yang, XP Cruz, A Penumetcha, P Hayes, E Pelletier, M Gabay, O Walsh, M Ferdinand, J Keane-Myers, A Choi, YW O'Shea, J Al-Shamkhani, A Kaplan, M Gery, I Siegel, R AF Meylan, Francoise Richard, Arianne Tan, Cuiyan Hawley, Eric Gomez-Rodriguez, Julio Goswami, Ritobrata Yang, Xiangping Cruz, Anthony Penumetcha, Pallavi Hayes, Erika Pelletier, Martin Gabay, Odile Walsh, Matthew Ferdinand, John Keane-Myers, Andrea Choi, Yongwon O'Shea, John Al-Shamkhani, Aymen Kaplan, Mark Gery, Igal Siegel, Richard TI The TNF-family ligand TL1A and its receptor DR3 promote T cell mediated allergic immunopathology by enhancing differentiation and pathogenicity of IL-9 producing T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Meylan, Francoise; Richard, Arianne; Hawley, Eric; Yang, Xiangping; Cruz, Anthony; Penumetcha, Pallavi; Hayes, Erika; Pelletier, Martin; Gabay, Odile; Ferdinand, John; O'Shea, John; Siegel, Richard] NIAMS, NIH, Bethesda, MD USA. [Tan, Cuiyan; Gery, Igal] NEI, NIH, Bethesda, MD 20892 USA. [Gomez-Rodriguez, Julio] NHGRI, NIH, Bethesda, MD 20892 USA. [Goswami, Ritobrata; Kaplan, Mark] Indiana Univ Sch Med, Bethesda, IN USA. [Keane-Myers, Andrea] Biol Naval Med Res Ctr, Ft Detrick, MD USA. [Al-Shamkhani, Aymen] Univ Southampton, Fac Med, Southhsmpton, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HYP2P.333 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500101 ER PT J AU Morozov, G Zhao, HY Mage, M Boyd, L Venna, R Norcross, M McMurtrey, C Hildebrand, W Schuck, P Jiang, JS Natarajan, K Margulies, D AF Morozov, Giora Zhao, Huaying Mage, Michael Boyd, Lisa Venna, Ramesh Norcross, Michael McMurtrey, Curtis Hildebrand, William Schuck, Peter Jiang, Jiansheng Natarajan, Kannan Margulies, David TI Direct interaction of recombinant TAPBPR with MHC-I molecules: stabilization of peptide-free MHC-I promotes high affinity peptide loading SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Morozov, Giora; Mage, Michael; Boyd, Lisa; Jiang, Jiansheng; Natarajan, Kannan; Margulies, David] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Zhao, Huaying; Schuck, Peter] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD USA. [Venna, Ramesh; Norcross, Michael] US FDA, Lab Immunol, Div Therapeut Prot, CDER, Bethesda, MD 20014 USA. [McMurtrey, Curtis; Hildebrand, William] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA APP5P.102 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500132 ER PT J AU Munitic, I Giardino-Torchia, ML Ashwell, J AF Munitic, Ivana Giardino-Torchia, Maria Letizia Ashwell, Jonathan TI Optineurin is dispensable for LPS- and Salmonella typhimurium-induced autophagy SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Munitic, Ivana] Univ Rijeka, Dept Biotechnol, Rijeka, Croatia. [Munitic, Ivana; Giardino-Torchia, Maria Letizia; Ashwell, Jonathan] NCI, LICB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA INM3P.412 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503223 ER PT J AU Myers, L Joedicke, J Carmody, A Messer, R Dittmer, U Kim, H AF Myers, Lara Joedicke, Jara Carmody, Aaron Messer, Ron Dittmer, Ulf Kim, Hasenkrug TI Mechanisms of regulatory T cell activation and expansion utilizing virus-specific CD8+T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Myers, Lara; Carmody, Aaron; Messer, Ron; Kim, Hasenkrug] NIH, Rocky Mt Labs, Hamilton, MT USA. [Joedicke, Jara; Dittmer, Ulf] Univ Duisburg Essen, Essen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504060 ER PT J AU Myles, I Datta, S AF Myles, Ian Datta, Sandip TI Transfer factor: forgotten, but not gone SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Myles, Ian; Datta, Sandip] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA MUC2P.934 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504035 ER PT J AU Nair, M Jang, J Barnes, M Le Gros, G Cooper, P Steel, C Nutman, T Lazar, M AF Nair, Meera Jang, Jessica Barnes, Mark Le Gros, Graham Cooper, Philip Steel, Cathy Nutman, Thomas Lazar, Mitchell TI The human protein resistin drives detrimental inflammatory monocyte responses in helminth infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Nair, Meera; Jang, Jessica; Barnes, Mark] Univ Calif Riverside, Riverside, CA 92521 USA. [Le Gros, Graham] Malaghan Inst, Wellington, New Zealand. [Cooper, Philip] Lab Invest Ecuador, Quito, Ecuador. [Steel, Cathy; Nutman, Thomas] NIH, Bethesda, MD 20892 USA. [Lazar, Mitchell] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA MPF7P.710 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503046 ER PT J AU Nakano, H Moran, T Nakano, K Whitehead, G Thomas, S Cook, D AF Nakano, Hideki Moran, Timothy Nakano, Keiko Whitehead, Gregory Thomas, Seddon Cook, Donald TI CCR2 promotes accumulation of conventional dendritic cells in the lung during inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Nakano, Hideki; Moran, Timothy; Nakano, Keiko; Whitehead, Gregory; Thomas, Seddon; Cook, Donald] NIEHS, Res Triangle Pk, NC 27709 USA. [Moran, Timothy] Univ N Carolina, Sch Med, Pediat, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA CAM4P.149 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502207 ER PT J AU Navid, F Layh-Schmitt, G Colbert, R AF Navid, Fatemeh Layh-Schmitt, Gerlinde Colbert, Robert TI Autophagy reduces the accumulation of misfolded HLA-B27 in a rat model of spondyloarthritis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Navid, Fatemeh; Layh-Schmitt, Gerlinde; Colbert, Robert] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA THER2P.951 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500014 ER PT J AU Ong, S Ligons, D Barin, J Wu, L Talor, M Diny, N Fontes, J Gebremariam, E Rose, N Cihakova, D AF Ong, SuFey Ligons, Davinna Barin, Jobert Wu, Lei Talor, Monica Diny, Nicola Fontes, Jillian Gebremariam, Elizabeth Rose, Noel Cihakova, Daniela TI Natural killer cells protect against cardiac inflammation and fibrosis by directly limiting eosinophilic accumulation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Ong, SuFey; Wu, Lei; Diny, Nicola; Fontes, Jillian] Johns Hopkins Bloomberg Sch Publ Hlth, Mol Microbiol & Immunol, Baltimore, MD USA. [Ong, SuFey] Benaroya Res Inst, Immunol Grp, Seattle, WA USA. [Barin, Jobert; Talor, Monica; Gebremariam, Elizabeth; Rose, Noel; Cihakova, Daniela] Johns Hopkins Univ, Sch Med, Pathol, Baltimore, MD USA. [Ligons, Davinna] NCI, NIH, Bethesda, MD 20892 USA. RI Cihakova, Daniela /A-9821-2017 OI Cihakova, Daniela /0000-0002-8713-2860 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA BA7P.144 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501263 ER PT J AU Park, JH Luckey, M Liu, Y Shaw, S AF Park, Jung-Hyun Luckey, Megan Liu, Yin Shaw, Stephen TI Constitutively active ezrin desensitizes IL-7 signaling and impairs T cell homeostasis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Park, Jung-Hyun; Luckey, Megan; Shaw, Stephen] NCI, Bethesda, MD 20892 USA. [Liu, Yin] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA LYM2P.735 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503231 ER PT J AU Paschall, A Zhang, RH Qi, CF Bardhan, K Peng, L Lu, GM Yang, JJ Merad, M McGaha, T Zhou, G Mellor, A Abrams, S Morse, H Ozato, K Xiong, HB Liu, KB AF Paschall, Amy Zhang, Rui-hua Qi, Chen-Feng Bardhan, Kankana Peng, Liang Lu, Geming Yang, Jianjun Merad, Miriam McGaha, Tracy Zhou, Gang Mellor, Andrew Abrams, Scott Morse, Herbert Ozato, Keiko Xiong, Huabao Liu, Kebin TI IRF8 expressed in T cells regulates GM-CSF expression to control myeloid derived suppressor cell differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Paschall, Amy; Bardhan, Kankana; Liu, Kebin] Georgia Regents Univ, Biochem & Mol Biol, Augusta, GA USA. [Paschall, Amy; Liu, Kebin] Charlie Norwood VA Med Ctr, Augusta, GA USA. [Paschall, Amy; McGaha, Tracy; Zhou, Gang; Mellor, Andrew; Liu, Kebin] Georgia Regents Univ, Canc Immunol Inflammat & Tolerance, Augusta, GA USA. [Zhang, Rui-hua; Peng, Liang; Lu, Geming; Yang, Jianjun; Merad, Miriam; Xiong, Huabao] Icahn Sch Med Mt Sinai, Immunol Inst, New York, NY 10029 USA. [Qi, Chen-Feng; Morse, Herbert] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA. [Abrams, Scott] Roswell Pk Canc Inst, Immunol, Buffalo, NY 14263 USA. [Ozato, Keiko] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Programs Genom Differentiat, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA TUM6P.955 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503112 ER PT J AU Patial, S Stumpo, D Huang, W Flake, G Blackshear, P AF Patial, Sonika Stumpo, Deborah Huang, Weichun Flake, Gordon Blackshear, Perry TI Genetic deletion of AU-rich region in the tristetraprolin (TTP) transcript increases TTP stability and expression and provides protection against inflammatory diseases SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Patial, Sonika; Stumpo, Deborah; Blackshear, Perry] NIEHS, Lab Signal Transduct, Durham, NC USA. [Huang, Weichun] NIEHS, Biostat Branch, Durham, NC USA. [Flake, Gordon] NIEHS, Lab Expt Pathol, Durham, NC USA. [Blackshear, Perry] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Blackshear, Perry] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA INM1P.433 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503295 ER PT J AU Paylakis, G Bergamaschi, C Valentin, A Kulkarni, V Jalah, R Rosati, M Alicea, C Sowder, R Chertova, E Felber, B AF Paylakis, George Bergamaschi, Cristina Valentin, Antonio Kulkarni, Viraj Jalah, Rashmi Rosati, Margherita Alicea, Candido Sowder, Raymond Chertova, Elena Felber, Barbara TI Use of heterodimeric IL-15 in immune therapeutic regimens against HIV-1 or SIV infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Paylakis, George; Bergamaschi, Cristina; Valentin, Antonio; Kulkarni, Viraj; Jalah, Rashmi; Rosati, Margherita; Alicea, Candido; Felber, Barbara] NCI, Ctr Canc Res, Frederick, MD 21701 USA. [Sowder, Raymond; Chertova, Elena] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VAC8P.1048 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503169 ER PT J AU Penaloza-MacMaster, P Barber, D Wherry, E Provine, N Teigler, JE Parenteau, L Blackmore, S Borducchi, E Larocca, R Yates, K Shen, H Haining, W Sommerstein, R Pinschewer, D Ahmed, R Barouch, D AF Penaloza-MacMaster, Pablo Barber, Daniel Wherry, E. Provine, Nicholas Teigler, Jeffrey E. Parenteau, Lily Blackmore, Stephen Borducchi, Erica Larocca, Rafael Yates, Kathleen Shen, Hao Haining, W. Sommerstein, Rami Pinschewer, Daniel Ahmed, Rafi Barouch, Dan TI LCMV-specific CD4 T cells induce immunopathology and impair immune protection following chronic LCMV infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Penaloza-MacMaster, Pablo; Provine, Nicholas; Teigler, Jeffrey E.; Parenteau, Lily; Blackmore, Stephen; Borducchi, Erica; Larocca, Rafael; Barouch, Dan] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA USA. [Barber, Daniel] NIAID, Parasit Dis Lab, Bethesda, MD USA. [Wherry, E.; Shen, Hao] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Wherry, E.; Shen, Hao] Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Yates, Kathleen; Haining, W.] Harvard Med Sch, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. [Sommerstein, Rami; Pinschewer, Daniel] Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland. [Sommerstein, Rami; Pinschewer, Daniel] Univ Geneva, WHO Collaborating Ctr Vaccine Immunol, Geneva, Switzerland. [Pinschewer, Daniel] Univ Basel, Dept Biomed Haus Peterspl, Div Expt Virol, Basel, Switzerland. [Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA USA. [Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Barouch, Dan] Ragon Inst MGH MIT & Harvard, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VIR1P.1132 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500022 ER PT J AU Placek, K Cui, KR Hu, GQ Lee, JE Wang, CC Konkel, J Zhang, DF Chen, WJ Ge, K Zhao, KJ AF Placek, Katarzyna Cui, Kairong Hu, Gangqing Lee, Ji-Eun Wang, Chaochen Konkel, Joanne Zhang, Dunfang Chen, WanJun Ge, Kai Zhao, Keji TI KMT2D histone methyltransferase modulates chromatin accessibility during regulatory T cell development SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Placek, Katarzyna; Cui, Kairong; Hu, Gangqing; Zhao, Keji] NHLBI, NIH, Bethesda, MD 20892 USA. [Lee, Ji-Eun; Wang, Chaochen; Ge, Kai] NIDDK, NIH, Bethesda, MD 20892 USA. [Konkel, Joanne] Univ Manchester, Manchester, Lancs, England. [Zhang, Dunfang; Chen, WanJun] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA LYM6P.714 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502109 ER PT J AU Rajagopalan, S Lee, E DuPrie, M Long, E AF Rajagopalan, Sumati Lee, Elizabeth DuPrie, Matthew Long, Eric TI TRAF6 and TAK1 control signals for a senescence response by an endosomal NK cell receptor SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Rajagopalan, Sumati; Lee, Elizabeth; DuPrie, Matthew; Long, Eric] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA INC2P.414 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502088 ER PT J AU Rua, R McGavern, D AF Rua, Rejane McGavern, Dorian TI Alternatively activated brain-resident macrophages rapidly acquire inflammatory properties following CNS infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Rua, Rejane; McGavern, Dorian] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA INC6P.301 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501308 ER PT J AU Rus, H Tegla, C Cudrici, C Nguyen, V Kruszewski, A Mekala, A Rus, V Badea, T AF Rus, Horea Tegla, Cosmin Cudrici, Cornelia Vinh Nguyen Kruszewski, Adam Mekala, Amurgam Rus, Violeta Badea, Tudor TI RGC-32 regulates T lymphocyte cell cycle activation in a phosphatidylinositol 3-kinase and IL-2-dependent manner SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Rus, Horea; Tegla, Cosmin; Cudrici, Cornelia; Vinh Nguyen; Kruszewski, Adam; Mekala, Amurgam; Rus, Violeta] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Rus, Horea; Tegla, Cosmin] Vet Adm Maryland Hlth Care Sysytem, Baltimore, MD USA. [Badea, Tudor] NEI, Retinal Circuit Dev & Genet Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA IRC8P.442 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504092 ER PT J AU Rus, V Nguyen, V Badea, T Cudrici, C Tegla, C Mekala, A Rus, H AF Rus, Violeta Vinh Nguyen Badea, Tudor Cudrici, Cornelia Tegla, Cosmin Mekala, Armugam Rus, Horea TI RGC-32 enhances suboptimal CD8 cytotoxic T cell effector function in acute graft versus host disease and promotes lupus-like disease in chronic graft versus host disease SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Rus, Violeta; Vinh Nguyen; Tegla, Cosmin; Mekala, Armugam; Rus, Horea] VAMHCS, Res Serv, Baltimore, MD USA. [Badea, Tudor] NEI, Retinal Circuit Dev & Genet Unit, N NRL, NIH, Bethesda, MD 20892 USA. [Cudrici, Cornelia] NIAMS, NIH, Bethesda, MD USA. [Rus, Violeta; Vinh Nguyen; Tegla, Cosmin; Mekala, Armugam; Rus, Horea] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA THER2P.965 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500009 ER PT J AU Saxena, A Xiao, ZX Yagita, H Larman, B Donner, T Hamad, AR AF Saxena, Ankit Xiao, Zuoxiang Yagita, Hideo Larman, Ben Donner, Thomas Hamad, Abdel Rahim TI FasL-expressing B cells are major players in type 1 diabetes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Saxena, Ankit; Larman, Ben; Donner, Thomas; Hamad, Abdel Rahim] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Xiao, Zuoxiang] NCI Frederick, Ctr Canc Res, Frederick, MD USA. [Yagita, Hideo] Juntendo Univ, Sch Med, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA BA6P.129 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500180 ER PT J AU Sckisel, G Mirsoian, A Tietze, J Monjazeb, A Blazar, B Wiltrout, R Murphy, W AF Sckisel, Gail Mirsoian, Annie Tietze, Julia Monjazeb, Arta Blazar, Bruce Wiltrout, Robert Murphy, William TI Strong systemic cancer immunostimulatory therapies cause stress-induced acute thymic involution SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Sckisel, Gail; Mirsoian, Annie; Tietze, Julia; Monjazeb, Arta; Murphy, William] UC Davis Sch Med, Dermatol, Sacramento, CA USA. [Blazar, Bruce] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Wiltrout, Robert] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VAC12P1114 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501018 ER PT J AU Seedhom, M David, A Hickman, H Bennink, J Yewdell, J AF Seedhom, Mina David, Alexandre Hickman, Heather Bennink, Jack Yewdell, Jonathan TI The RiboPuromycylation Method Reveals Rapid IL12-Dependent Antigen-Independent Activation of Bone Marrow Virtual Memory T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Seedhom, Mina; Hickman, Heather; Bennink, Jack; Yewdell, Jonathan] NIAID, Rockville, MD USA. [David, Alexandre] Inst Genom Fonct, Oncol, Montpellier, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA INC1P.403 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503168 ER PT J AU Sgourakis, N AF Sgourakis, Nikolaos TI Mapping the interaction footprint of Viral Immunoevasins on a "platform" MHC-1 molecule using solution NMR spectroscopy SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Sgourakis, Nikolaos] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA APP2P.102 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502014 ER PT J AU Siebenlist, U Claudio, E Tassi, I Wang, HS AF Siebenlist, Ulrich Claudio, Estefania Tassi, Ilaria Wang, Hongshan TI Dendritic cells are functionally relevant targets of IL-25 in allergic lung inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Siebenlist, Ulrich; Claudio, Estefania; Tassi, Ilaria; Wang, Hongshan] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HYP2P.320 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500110 ER PT J AU Silvestre, I Peterson, D Redelman, D Anderson, S Hudig, D AF Silvestre, Isabel Peterson, Daniel Redelman, Douglas Anderson, Stephen Hudig, Dorothy TI Assessment of the Fc receptor CD16A of NK cells of CFS patients for potential to mediate ADCC activity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Silvestre, Isabel; Hudig, Dorothy] Univ Nevada, Sch Med, Microbiol & Immunol, Reno, NV 89557 USA. [Peterson, Daniel] Sierra Internal Med, Incline, NV USA. [Redelman, Douglas] Univ Nevada, Sch Med, Physiol, Reno, NV 89557 USA. [Anderson, Stephen] NCI, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HUM1P.303 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500333 ER PT J AU Skarzynski, M Butera, V Lindorfer, M Vire, B Farooqui, M Rader, C Taylor, R Wiestner, A AF Skarzynski, Martin Butera, Vicent Lindorfer, Margaret Vire, Berengere Farooqui, Mohammed Rader, Christoph Taylor, Ronald Wiestner, Adrian TI Targeting deposited complement component C3d to potentiate monoclonal antibody cancer therapy SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Skarzynski, Martin; Butera, Vicent; Vire, Berengere; Farooqui, Mohammed; Wiestner, Adrian] NHLBI, North Bethesda, MD USA. [Lindorfer, Margaret; Taylor, Ronald] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Rader, Christoph] Scripps Res Inst, Jupiter, FL USA. [Rader, Christoph] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VAC3P.1057 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501170 ER PT J AU Smith, C Vivekanandan-Giri, A Playford, M Berthier, C Kretzler, M Mehta, N Pennathur, S Kaplan, M AF Smith, Carolyne Vivekanandan-Giri, Anuradha Playford, Martin Berthier, Celine Kretzler, Matthias Mehta, Nehal Pennathur, Subramaniam Kaplan, Mariana TI Modulation of macrophage responses by aberrant lipoproteins in chronic inflammatory diseases. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Smith, Carolyne] Univ Michigan, Gaithersburg, MD USA. [Kaplan, Mariana] NIH, Syst Autoimmun Branch, Bethesda, MD 20892 USA. [Vivekanandan-Giri, Anuradha; Berthier, Celine; Kretzler, Matthias; Pennathur, Subramaniam] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Playford, Martin; Mehta, Nehal] NHLBI, Sect Inflammat & Cardiometab Dis, NIH, Bethesda, MD 20892 USA. [Smith, Carolyne] NIAMS, Syst Autoimmun Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HUM3P.241 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500155 ER PT J AU Srivastava, A Paria, B Chandran, S Kammula, U AF Srivastava, Abhishek Paria, Biman Chandran, Smita Kammula, Udai TI Ex vivo co-stimulatory 4-1BBL enhances the antitumor capacity of antigen specific CD8+T cells after adoptive transfer in NSG mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Srivastava, Abhishek; Paria, Biman; Chandran, Smita; Kammula, Udai] NCI, Surg Branch, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VAC7P.1042 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500289 ER PT J AU St Leger, A Caspi, R AF St Leger, Anthony Caspi, Rachel TI Ocular microflora modulates IL-17 and neutrophil recruitment within the conjunctiva associated lymphoid tissue SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [St Leger, Anthony; Caspi, Rachel] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA MUC9P.739 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502319 ER PT J AU Stevanovic, S Campbell, T Draper, L Langhan, M Somerville, R Wunderlich, J Kwong, ML Kerkar, S Yang, J Sherry, R Kammula, U Rosenberg, S Hinrichs, C AF Stevanovic, Sanja Campbell, Tracy Draper, Lindsey Langhan, Michelle Somerville, Robert Wunderlich, John Kwong, Mei Li Kerkar, Sid Yang, James Sherry, Richard Kammula, Udai Rosenberg, Steven Hinrichs, Christian TI Adoptive transfer of autologous tumor infiltrating lymphocytes in metastatic human papilloma virus-induced carcinoma SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Stevanovic, Sanja; Campbell, Tracy; Draper, Lindsey; Langhan, Michelle; Somerville, Robert; Wunderlich, John; Kwong, Mei Li; Yang, James; Sherry, Richard; Kammula, Udai; Rosenberg, Steven; Hinrichs, Christian] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Kerkar, Sid] NCI, Pathol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VAC7P.1040 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500285 ER PT J AU Su, XL Zhang, JL Yu, L Xing, ZW Liang, JQ Nanda, A AF Su, Xiulan Zhang, Jialing Yu, Lan Xing, Zhiwei Liang, Junqing Nanda, A. TI Identification of miRNA-338-5P as an effector of the tumor suppressor activity of immunized anticancer bioactive peptide-3 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Su, Xiulan; Zhang, Jialing; Yu, Lan; Liang, Junqing] Inner Mongolia Peoples Hosp, Clin Med Res Ctr, Hohhot, Peoples R China. [Zhang, Jialing] NIDCD, Head & Neck Surg Branch, NIH, Betheda, MD USA. [Xing, Zhiwei] Inner Mongolia Med Univ, Affiliated Hosp, Clin Med Res Ctr, Hohhot, Peoples R China. [Nanda, A.] Inner Mongolia Med Univ, Affiliated Hosp, Clin Med Res Ctr, Hohhot, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA TUM2P.1036 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500248 ER PT J AU Sun, C Lee, YS Lipsky, A Farooqui, M Herman, S Salem, D Stetler-Stevenson, M Yuan, C Aue, G Wiestner, A AF Sun, Clare Lee, Yuh Shan Lipsky, Andrew Farooqui, Mohammed Herman, Sarah Salem, Dalia Stetler-Stevenson, Maryalice Yuan, Constance Aue, Georg Wiestner, Adrian TI Effects of the Bruton's tyrosine kinase inhibitor ibrutinib on humoral immunity in patients with chronic lymphocytic leukemia SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Sun, Clare; Lee, Yuh Shan; Farooqui, Mohammed; Herman, Sarah; Aue, Georg; Wiestner, Adrian] NHLBI, Hematol, NIH, Bldg 10, Bethesda, MD 20892 USA. [Lipsky, Andrew] Montefiore Med Ctr, Internal Med, 111 E 210th St, Bronx, NY 10467 USA. [Salem, Dalia; Stetler-Stevenson, Maryalice; Yuan, Constance] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Salem, Dalia/R-9314-2016 OI Salem, Dalia/0000-0002-4209-2260 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HUM1P.258 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500304 ER PT J AU Tajima, M Fuss, I Kitani, A Strober, W AF Tajima, Masaki Fuss, Ivan Kitani, Atsushi Strober, Warren TI Fungal recognition by Dectin-1 on dendritic cells induces IL-10 producing CD4(+) T cells by GATA3 / C/EBP-beta pathway SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Tajima, Masaki; Fuss, Ivan; Kitani, Atsushi; Strober, Warren] NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA MPF4P.733 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503012 ER PT J AU Thornton, A Sebastian, M Korty, P Lopez-Ocasio, M Shevach, E AF Thornton, Angela Sebastian, Mathew Korty, Patricia Lopez-Ocasio, Maria Shevach, Ethan TI Expression of Helios is required for the differentiation of activated/effector T regulatory cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Thornton, Angela; Sebastian, Mathew; Korty, Patricia; Lopez-Ocasio, Maria; Shevach, Ethan] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA IRC11P.438 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504003 ER PT J AU Tosh, K Singer, S Sher, A Jankovic, D AF Tosh, Kevin Singer, Steven Sher, Alan Jankovic, Dragana TI Toxoplasma gondii elicits a phagocytosis dependent pro-inflammatory cytokine response in human primary myeloid cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Tosh, Kevin; Singer, Steven] Georgetown Univ, Microbiol & Immunol, Washington, DC USA. [Tosh, Kevin; Sher, Alan; Jankovic, Dragana] NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA INC4P.327 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404500340 ER PT J AU Tse, H Anderson, B Ganini, D Mason, R AF Tse, Hubert Anderson, Brian Ganini, Douglas Mason, Ron TI Immuno-spin trapping to detect immune derived free radicals in type 1 diabetes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Tse, Hubert; Anderson, Brian] Univ Alabama Birmingham, Birmingham, AL USA. [Ganini, Douglas; Mason, Ron] NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA TECH2P.903 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504174 ER PT J AU Watanabe, M Hodes, R AF Watanabe, Masashi Hodes, Richard TI Cellular and molecular basis of Ag-specific and Ag-nonspecific T-dependent antibody responses in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Watanabe, Masashi; Hodes, Richard] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA IRC8P.447 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504093 ER PT J AU Williams, J Jeon, H Hodes, R AF Williams, Joy Jeon, Hyein Hodes, Richard TI Thymocyte requirements for normal thymic medullary epithelial cell development SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Williams, Joy; Jeon, Hyein; Hodes, Richard] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HEM7P.227 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504208 ER PT J AU Witter, A Break, T Indramohan, M Mummert, M Berg, R AF Witter, Alexandra Break, Timothy Indramohan, Mohanalaxmi Mummert, Mark Berg, Rance TI Extracellular superoxide dismutase promotes immature neutrophil egress from the bone marrow SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Witter, Alexandra; Berg, Rance] Univ North Texas, Hlth Sci Ctr, Cell Biol & Immunol, Ft Worth, TX USA. [Mummert, Mark] Univ North Texas, Hlth Sci Ctr, Psychiat & Behav Hlth, Ft Worth, TX USA. [Break, Timothy] NIAID, NIH, Bethesda, MD 20892 USA. [Indramohan, Mohanalaxmi] Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA INC6P.303 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501316 ER PT J AU Yang, Q Xue, HHH Bhandoola, A AF Yang, Qi Xue, Hai-Hui Howard Bhandoola, Avinash TI a conversed gene regulatory pathway underwrites the development of innate lymphoid cells and adaptive T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Yang, Qi] Univ Penn, Philadelphia, PA 19104 USA. [Bhandoola, Avinash] NCI, NIH, Bethesda, MD 20892 USA. [Xue, Hai-Hui Howard] Univ Iowa, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA HEM8P.239 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502031 ER PT J AU Yen, JH Kong, W Hooper, K Emig, F Rahbari, K Kuo, PC Scofield, B Ganea, D AF Yen, Jui-Hung Kong, Weimin Hooper, Kirsten Emig, Fran Rahbari, Kate Kuo, Ping-Chang Scofield, Barbara Ganea, Doina TI Differential effects of IFN beta on IL-12, IL-23, and IL-10 expression in TLR-stimulated dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Yen, Jui-Hung; Kuo, Ping-Chang; Scofield, Barbara] Indiana Univ Sch Med, Microbiol & Immunol, Ft Wayne, IN USA. [Kong, Weimin; Hooper, Kirsten; Emig, Fran; Ganea, Doina] Temple Univ, Sch Med, Microbiol & Immunol, Philadelphia, PA 19122 USA. [Rahbari, Kate] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA BA7P.157 PG 2 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404501266 ER PT J AU Younes, S Shive, C Reynaldi, A Freeman, M Panigrahi, S Estes, J Anderson, J Schacker, T Davenport, M McCune, J Hunt, P Lee, S Serrano-Villar, S Canaday, D Cameron, C Sekaly, RP Rodriguez, B Sieg, S Lederman, M AF Younes, Souheil Shive, Carey Reynaldi, Arnold Freeman, Michael Panigrahi, Soumya Estes, Jacob Anderson, Jodi Schacker, Timothy Davenport, Miles McCune, Joseph Hunt, Peter Lee, Sulggi Serrano-Villar, Sergio Canaday, David Cameron, Cheryl Sekaly, Rafick-Pierre Rodriguez, Benigno Sieg, Scott Lederman, Michael TI IL-15 drives CD8 T cell cycling and differentiation in chronic HIV-1 infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Younes, Souheil; Shive, Carey; Panigrahi, Soumya; Cameron, Cheryl; Sekaly, Rafick-Pierre; Rodriguez, Benigno; Sieg, Scott; Lederman, Michael] Case Western Reserve Univ, Infect Dis, Cleveland, OH 44106 USA. [Freeman, Michael] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Canaday, David] Cleveland VA, Cleveland, OH USA. [McCune, Joseph] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Estes, Jacob] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA. [Anderson, Jodi; Schacker, Timothy] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Reynaldi, Arnold; Davenport, Miles] Univ New S Wales, Ctr Vasc Res, Sydney, NSW, Australia. [Hunt, Peter; Lee, Sulggi] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Serrano-Villar, Sergio] Univ Hosp Ramon y Cajal, Dept Infect Dis, Madrid, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA VIR6P.1162 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404505004 ER PT J AU Zander, R Obeng-Adjei, N Guthmiller, J Kulu, D Li, J Ongoiba, A Traore, B Crompton, P Butler, N AF Zander, Ryan Obeng-Adjei, Nyamekye Guthmiller, Jenna Kulu, Divine Li, Jun Ongoiba, Aissata Traore, Boubacar Crompton, Peter Butler, Noah TI Co-inhibitory and co-stimulatory crosstalk regulates helper T cell differentiation and humoral immunity during Plasmodium infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Zander, Ryan; Guthmiller, Jenna; Kulu, Divine; Butler, Noah] OUHSC, Microbiol & Immunol, Oklahoma City, OK USA. [Obeng-Adjei, Nyamekye; Crompton, Peter] NIAID, Lab Immunogenet, NIH, Rockville, MD USA. [Li, Jun] Univ Oklahoma, Dept Chem & Biochem, Norman, OK 73019 USA. [Ongoiba, Aissata; Traore, Boubacar] Univ Sci Tech & Technol Bamako, Mali Int Ctr Excellence Res, Bamako, Mali. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA MPF5P.742 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502121 ER PT J AU Zanin-Zhorov, A Flynn, R Luznik, L Nyuydzefe, M Panoskaltsis-Mortari, A Du, J Goodman, K Weiss, J Chen, W Serody, J MacDonald, K Hill, G O'Shea, J Waksal, S Blazar, B AF Zanin-Zhorov, Alexandra Flynn, Ryan Luznik, Leo Nyuydzefe, Melanie Panoskaltsis-Mortari, Angela Du, Jing Goodman, Katelyn Weiss, Jonathan Chen, Wei Serody, Jonathan MacDonald, Kelli Hill, Geoffrey O'Shea, John Waksal, Samuel Blazar, Bruce TI Selective ROCK2 inhibitor reverses experimental chronic graft-versus-host disease via concurrent regulation of STAT3/STAT5 phosphorylation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Zanin-Zhorov, Alexandra; Nyuydzefe, Melanie; Weiss, Jonathan; Chen, Wei; Waksal, Samuel] Kadmon Res Inst, New York, NY USA. [Flynn, Ryan; Panoskaltsis-Mortari, Angela; Du, Jing; Goodman, Katelyn; Blazar, Bruce] Univ Minnesota, Div Blood & Marrow Transplantat, Minneapolis, MN USA. [Luznik, Leo] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Serody, Jonathan] Univ N Carolina, Canc Ctr, Chapel Hill, NC USA. [MacDonald, Kelli; Hill, Geoffrey] Queensland Inst Med Res, Brisbane, ACT, Australia. [O'Shea, John] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504239 ER PT J AU Zhang, H Robins, H Mackall, C AF Zhang, Hua Robins, Harlan Mackall, Crystal TI Recombinant human IL7 enhances naive and T stem cell memory reconstitution and enhances repertoire diversity following cytotoxic chemotherapy SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Robins, Harlan] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Mackall, Crystal] NCI, Bethesda, MD 20892 USA. [Zhang, Hua] NCI, POB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA LYM5P.705 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404502244 ER PT J AU Zhang, JL Chen, H Yang, XP Guven, E Nussinov, R Chen, Z VanWaes, C AF Zhang, Jialing Chen, Hui Yang, Xinping Guven, Emine Nussinov, Ruth Chen, Zhong VanWaes, Carter TI Defective TRAF3 modulates alternative NF-kB signaling and cytokine expression to promote cancer cell survival in HPV positive head and neck cancer SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Guven, Emine] Koc Univ, Dept Chem & Biol Engn, Istanbul, Turkey. [Zhang, Jialing; Chen, Hui; Yang, Xinping; Chen, Zhong; VanWaes, Carter] NIDCD, Head & Neck Surg Branch, NIH, Bethesda, MD USA. [Nussinov, Ruth] NCI, Nanobiol Program, Computat Struct Biol Grp, Ctr Canc Res,NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404504309 ER PT J AU Zhong, C Hu, GQ Zhao, KJ AF Zhong, Chao Hu, Gangqing Zhao, Keji TI GATA-3 regulates the development of ILC3 subsets at multiple stages SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists (IMMUNOLOGY) CY MAY 08-12, 2015 CL New Orleans, LA SP Amer Assoc Immunologists C1 [Zhong, Chao] NIAID, Mol & Cellular Immunoregulat Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Hu, Gangqing; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2015 VL 194 SU 1 MA LYM2P.721 PG 1 WC Immunology SC Immunology GA DQ7RG UT WOS:000379404503236 ER PT J AU Dye, BA Hsu, KLC Afful, J AF Dye, Bruce A. Hsu, Kuei-Ling C. Afful, Joseph TI Prevalence and Measurement of Dental Caries in Young Children SO PEDIATRIC DENTISTRY LA English DT Article DE EARLY CHILDHOOD CARIES; NURSING BOTTLE CARIES; TOOTH DECAY; NHANES; EPIDEMIOLOGY ID EARLY-CHILDHOOD CARIES; ORAL-HEALTH COMPONENT; RANDOMIZED CONTROLLED-TRIAL; EXAMINATION SURVEY NHANES; PRESCHOOL-CHILDREN; RISK-FACTORS; NATIONAL-HEALTH; UNITED-STATES; BEHAVIORAL DETERMINANTS; SOCIOECONOMIC-STATUS AB Purpose: Dental caries in preschool children was historically considered to have a unique and more intense pattern of decoy and was known by a variety of terms. In 1999, the term early childhood caries (ECC), along with a classification system, was proposed to facilitate epidemiologic research of dental caries in young children. The purpose of this study was to assess the impact of those early childhood caries recommendations on the prevalence and measurement of caries in preschool children. Methods: A systematic search of the MEDLINE database was performed. Key search words included: ECC, dental decay, dental caries, carious dentin, baby bottle tooth decay, nursing caries, maxillary anterior caries, and labial caries. English language studies and studies on more than 100 children younger than six years old were eligible for selection. National Health and Nutrition Examination Survey data collected from 1988 to 1994, 1999 to 2004, and 2011 to 2072 were used to assess ECC prevalence using different operational definitions. Results: There were 87 articles selected for this review. The term ECC was used in 55 percent of the selected articles as the primary outcome measure. The majority of studies used a cross-section study design, but diagnostic criteria varied greatly. Caries experience in young children may be shifting away from majority of untreated surfaces to a majority of restored surfaces. Little difference was observed by dental surface type in the distribution of decayed and filled surfaces in primary teeth. Conclusions: Although the term early childhood caries is widely used, varied use of diagnostic criteria and operational definitions continue to limit comparability across studies. Emerging changes in the proportion of decayed and filled surfaces in the United States also raises questions regarding the ECC case definition limiting our ability to understand the epidemiology of dental caries in preschool children. C1 [Dye, Bruce A.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Hsu, Kuei-Ling C.] Univ Maryland, Sch Dent, Div Pediat Dent, Baltimore, MD 21201 USA. [Afful, Joseph] Ctr Dis Control & Prevent, Harris Corp, Natl Ctr Hlth Stat, Hyattsville, MD USA. RP Dye, BA (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. EM bruce.dye@nih.gov NR 108 TC 11 Z9 11 U1 4 U2 9 PU AMER ACAD PEDIATRIC DENTISTRY PI CHICAGO PA 211 E CHICAGO AVENUE SUITE 1036, CHICAGO, IL 60611-2616 USA SN 0164-1263 EI 1942-5473 J9 PEDIATR DENT JI Pediatr. Dent. PD MAY-JUN PY 2015 VL 37 IS 3 BP 200 EP 216 PG 17 WC Dentistry, Oral Surgery & Medicine; Pediatrics SC Dentistry, Oral Surgery & Medicine; Pediatrics GA DL6DO UT WOS:000375729600002 PM 26063550 ER PT J AU Dagur, PK Mccoy, JP AF Dagur, Pradeep K. Mccoy, J. Philip, Jr. TI Endothelial-binding, proinflammatory T cells identified by MCAM (CD146) expression: Characterization and role in human autoimmune diseases SO AUTOIMMUNITY REVIEWS LA English DT Review DE CD146; MCAM Th17; Tc17; Rheumatoid arthritis; Psoriasis; Multiple sclerosis; EPIC T cell; lymphocyte ID MESENCHYMAL STEM-CELLS; HELPER 17 CELLS; PSORIATIC-ARTHRITIS; ADHESION MOLECULE; SIGNALING PATHWAY; PERIPHERAL-BLOOD; PROGENITOR CELLS; CD8+T CELLS; LYMPHOCYTES; ACTIVATION AB A subset of T cells defined by the cell surface expression of MCAM (CD146) has been identified in the peripheral circulation of healthy individuals. These cells comprise approximately 3% of the pool of circulating T cells, have an effector memory phenotype, and are capable of producing several cytokines. Notably, the MCAM positive cells are enhanced for IL-17 production compared to MCAM negative effector memory T cells. These cells are committed to IL-17 production and do not require in vitro polarization with exogenous cytoldnes. MCAM positive T cells also demonstrate an increased ability to bind to endothelial monolayers. In numerous autoimmune diseases these cells are found at increased proportions in the peripheral circulation, and at the sites of active inflammation in patients with autoimmune disease, these cells appear in large numbers and are major contributors to IL-17 production. Studies to date have been performed with human subjects and it is uncertain if appropriate mouse models exist for this cell type. These cells could represent early components of the adaptive immune response and serve as targets of therapy in these diseases, although much work remains to be performed in order to discern the exact nature and function of these cells. Published by Elsevier B.V. C1 [Dagur, Pradeep K.; Mccoy, J. Philip, Jr.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Mccoy, JP (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr,MSC 1357, Bethesda, MD 20892 USA. EM mccoyjp@mail.nih.gov FU intramural reserch program of the National Heart, Lung, and Blood Institute of NIH FX This work was supported by the intramural reserch program of the National Heart, Lung, and Blood Institute of NIH. The authors would like to thank numerous collaborators for providing their clinical samples as well as valuable advice and insight: Robert S Nussenblatt, H Nida Sen, Warren Strober, Michael Yao, Bibi Bielekova, Mark Gourley, Nehal N Mehta, Angelique Biancotto, and Shawn Rose. NR 53 TC 2 Z9 4 U1 3 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9972 EI 1873-0183 J9 AUTOIMMUN REV JI Autoimmun. Rev. PD MAY PY 2015 VL 14 IS 5 BP 415 EP 422 DI 10.1016/j.autrev.2015.01.003 PG 8 WC Immunology SC Immunology GA CF6JS UT WOS:000352663600007 PM 25595133 ER PT J AU Aceti, M Creson, TK Vaissiere, T Rojas, C Huang, WC Wang, YX Petralia, RS Page, DT Miller, CA Rumbaugh, G AF Aceti, Massimiliano Creson, Thomas K. Vaissiere, Thomas Rojas, Camilo Huang, Wen-Chin Wang, Ya-Xian Petralia, Ronald S. Page, Damon T. Miller, Courtney A. Rumbaugh, Gavin TI Syngap1 Haploinsufficiency Damages a Postnatal Critical Period of Pyramidal Cell Structural Maturation Linked to Cortical Circuit Assembly SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Autism spectrum disorder; Development; Epilepsy; Intellectual disability; Mouse model; Synapse; Syngap1 ID DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDERS; GTPASE-ACTIVATING PROTEIN; INTELLECTUAL DISABILITY; SYNAPTIC PLASTICITY; NEUROPSYCHIATRIC DISORDERS; MENTAL-RETARDATION; NEURONS; CORTEX; SCHIZOPHRENIA AB BACKGROUND: Genetic haploinsufficiency of SYNGAP1/Syngap1 commonly occurs in developmental brain disorders, such as intellectual disability, epilepsy, schizophrenia, and autism spectrum disorder. Thus, studying mouse models of Syngap1 haploinsufficiency may uncover pathologic developmental processes common among distinct brain disorders. METHODS: A Syngap1 haploinsufficiency model was used to explore the relationship between critical period dendritic spine abnormalities, cortical circuit assembly, and the window for genetic rescue to understand how damaging mutations disrupt key substrates of mouse brain development. RESULTS: Syngap1 mutations broadly disrupted a developmentally sensitive period that corresponded to the period of heightened postnatal cortical synaptogenesis. Pathogenic Syngap1 mutations caused a coordinated acceleration of dendrite elongation and spine morphogenesis and pruning of these structures in neonatal cortical pyramidal neurons. These mutations also prevented a form of developmental structural plasticity associated with experience-dependent reorganization of brain circuits. Consistent with these findings, Syngap1 mutant mice displayed an altered pattern of long-distance synaptic inputs into a cortical area important for cognition. Interestingly, the ability to genetically improve the behavioral endophenotype of Syngap1 mice decreased slowly over postnatal development and mapped onto the developmental period of coordinated dendritic insults. CONCLUSIONS: Pathogenic Syngap1 mutations have a profound impact on the dynamics and structural integrity of pyramidal cell postsynaptic structures known to guide the de novo wiring of nascent cortical circuits. These findings support the idea that disrupted critical periods of dendritic growth and spine plasticity may be a common pathologic process in developmental brain disorders. C1 [Aceti, Massimiliano; Creson, Thomas K.; Vaissiere, Thomas; Rojas, Camilo; Huang, Wen-Chin; Page, Damon T.; Miller, Courtney A.; Rumbaugh, Gavin] Scripps Res Inst, Dept Neurosci, Jupiter, FL USA. [Vaissiere, Thomas; Miller, Courtney A.] Scripps Res Inst, Dept Metab & Aging, Jupiter, FL USA. [Wang, Ya-Xian; Petralia, Ronald S.] NIDCD, Adv Imaging Core, NIH, Bethesda, MD USA. RP Rumbaugh, G (reprint author), Scripps Florida, 130 Scripps Way, Jupiter, FL 33458 USA. EM grumbaug@scripps.edu OI Aceti, Massimiliano/0000-0002-6632-1398 FU National Institute for Neurological Disorders and Stroke [R01NS064079]; National Institute for Mental Health [R01MH096847]; National Institute for Drug Abuse [R01 DA034116, R03 DA033499]; National Institute on Deafness and Other Communication Disorders/National Institutes of Health Intramural Research Program; State of Florida FX This work was supported by grants to GR from The National Institute for Neurological Disorders and Stroke (R01NS064079) andThe National Institute for Mental Health (R01MH096847). CAM was supported by grants from the National Institute for Drug Abuse (R01 DA034116; R03 DA033499). Y-XW and RSP were supported by the National Institute on Deafness and Other Communication Disorders/National Institutes of Health Intramural Research Program. W-CH and DTP were supported by gift funds from Mrs. Nancy Lurie Marks. GR, CAM, and DTP were supported by the State of Florida. NR 43 TC 5 Z9 5 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 BP 805 EP 815 DI 10.1016/j.biopsych.2014.08.001 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CE8LM UT WOS:000352093800007 PM 25444158 ER PT J AU Wnorowski, A Sadowska, M Paul, RK Singh, NS Boguszewska-Czubara, A Jimenez, L Abdelmohsen, K Toll, L Jozwiak, K Bernier, M Wainer, IW AF Wnorowski, Artur Sadowska, Mariola Paul, Rajib K. Singh, Nagendra S. Boguszewska-Czubara, Anna Jimenez, Lucita Abdelmohsen, Kotb Toll, Lawrence Jozwiak, Krzysztof Bernier, Michel Wainer, Irving W. TI Activation of beta 2-adrenergic receptor by (R,R ')-4 '-methoxy-1-naphthylfenoterol inhibits proliferation and motility of melanoma cells SO CELLULAR SIGNALLING LA English DT Article DE Beta2 adrenoreceptor selective agonist; Melanocyte; Metastasis; Beta blocker; Migration; Melanocortin 1 receptor ID MOLECULAR-FIELD ANALYSIS; DEPENDENT PROTEIN-KINASE; FENOTEROL DERIVATIVES; STIMULATING HORMONE; BETA(2)-ADRENERGIC RECEPTOR; KERATINOCYTE MIGRATION; METASTATIC MELANOMA; MALIGNANT-MELANOMA; CAMP; PHOSPHORYLATION AB (R,R')-4'-methoxy-1-naphthylfenoterol [(R,R')-MNF] is a highly-selective beta(2) adrenergic receptor (beta(2)-AR) agonist. Incubation of a panel of human-derived melanoma cell lines with (R,R')-MNF resulted in a dose- and time-dependent inhibition of motility as assessed by in vitro wound healing and xCELLigence migration and invasion assays. Activity of (R,R')-MNF positively correlated with the beta(2)-AR expression levels across tested cell lines. The anti-motility activity of (R,R')-MNF was inhibited by the beta(2)-AR antagonist ICI-118,551 and the protein kinase A inhibitor H-89. The adenylyl cyclase activator forskolin and the phosphodiesterase 4 inhibitor Ro 20-1724 mimicked the ability of (R,R')-MNF to inhibit migration of melanoma cell lines in culture, highlighting the importance of cAMP for this phenomenon. (R,R')-MNF caused significant inhibition of cell growth in beta(2)-AR-expressing cells as monitored by radiolabeled thymidine incorporation and xCELLigence system. The MEK/ERK cascade functions in cellular proliferation, and constitutive phosphorylation of MEK and ERK at their active sites was significantly reduced upon beta(2)-AR activation with (R,R')-MNF. Protein synthesis was inhibited concomitantly both with increased eEF2 phosphorylation and lower expression of tumor cell regulators, EGF receptors, cyclin A and MMP-9. Taken together, these results identified beta(2)-AR as a novel potential target for melanoma management, and (R,R')-MNF as an efficient trigger of anti-tumorigenic cAMP/PKA-dependent signaling in beta(2)-AR-expressing lesions. Published by Elsevier Inc. C1 [Wnorowski, Artur; Jozwiak, Krzysztof] Med Univ Lublin, Dept Chem, PL-20093 Lublin, Poland. [Wnorowski, Artur; Paul, Rajib K.; Singh, Nagendra S.; Wainer, Irving W.] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA. [Sadowska, Mariola] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Boguszewska-Czubara, Anna] Med Univ Lublin, Dept Med Chem, PL-20093 Lublin, Poland. [Jimenez, Lucita] SRI Int, Menlo Pk, CA 94025 USA. [Abdelmohsen, Kotb] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Toll, Lawrence] Torrey Pines Inst Mol Studies, Port St Lucie, FL 34987 USA. [Bernier, Michel] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. RP Bernier, M (reprint author), NIA, Translat Gerontol Branch, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM artur.wnorowski@gmail.com; mariolas349@gmail.com; rajibkpaul@gmail.com; nagendra.singh@nih.gov; anna.boguszewska-czubara@am.lublin.pl; lucita.jimenez@sri.com; abdelmohsenk@grc.nia.nih.gov; ltoll@tpims.org; krzysztof.jozwiak@umlub.pl; Bernierm@mail.nih.gov; iwwainer@mitchellwoods.com RI Singh, Nagendra/K-8966-2015 FU Intramural Research Program of the National Institute on Aging/NIH; NIA/NIH [N01-AG-3-1009]; Foundation for Polish Science [TEAM 2009-4/5] FX This work was supported by funds from the Intramural Research Program of the National Institute on Aging/NIH, NIA/NIH (contract N01-AG-3-1009) and the Foundation for Polish Science (TEAM 2009-4/5 programme). NR 60 TC 2 Z9 2 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 EI 1873-3913 J9 CELL SIGNAL JI Cell. Signal. PD MAY PY 2015 VL 27 IS 5 BP 997 EP 1007 DI 10.1016/j.cellsig.2015.02.012 PG 11 WC Cell Biology SC Cell Biology GA CE7RG UT WOS:000352038900012 PM 25703025 ER PT J AU Harpaz, Y Robinson, SE Medvedovsky, M Goldstein, A AF Harpaz, Yuval Robinson, Stephen E. Medvedovsky, Mordekhay Goldstein, Abraham TI Improving the excess kurtosis (g(2)) method for localizing epileptic sources in magnetoencephalographic recordings SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Epilepsy; Beamforming; Kurtosis; Spike; Source localization ID SYNTHETIC-APERTURE MAGNETOMETRY; INTRACTABLE EPILEPSY; INTERICTAL SPIKES; MEG; LOCALIZATION; CHILDREN; FOCI; EEG AB Objective: To suggest ways to apply the excess kurtosis estimator g(2), in the detection of epileptic activity with magnetoencephalography, while avoiding its bias towards detecting high-amplitude, infrequent events. Methods: Synthetic aperture magnetometry (SAM), combined with g2, was applied using window lengths ranging from 0.125 s to 32 s and with sum and maximum metrics on simulated data and recordings of two focal epilepsy patients. Results: Comparing sources with different spike rates (two per second and one per 2 s), the sum metric was most efficient when using a window of 0.25 s. Simulations showed that the sum metric is insensitive to spike frequency when the window includes more than one spike. SAM(g2) images from long segments with maximum metric resulted in misleading images, showing the strongest activity away from the lesions. Conclusions: Using a sliding window and the sum metric is beneficial when imaging interictal spikes and status epilepticus. Windows should be short enough not to include more than one interictal event. For continuous events such as electrographic seizures windows should contain baseline data and the epileptic event. Significance: The sliding window and metric should be set according to the suggested guidelines when using SAM(g2) for presurgical evaluation. (C) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Harpaz, Yuval; Goldstein, Abraham] Bar Ilan Univ, Gonda Brain Res Ctr, Ramat Gan, Israel. [Robinson, Stephen E.] NIMH, MEG Core Facil, NIH, Bethesda, MD 20892 USA. [Medvedovsky, Mordekhay] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Brain Funct Imaging Unit, IL-69978 Tel Aviv, Israel. [Goldstein, Abraham] Bar Ilan Univ, Dept Psychol, Ramat Gan, Israel. [Medvedovsky, Mordekhay] Univ Helsinki, Cent Hosp, BioMag Lab, Helsinki, Finland. RP Harpaz, Y (reprint author), Bar Ilan Univ, Gonda Multidisciplinary Brain Res Inst, Max & Anna Webb St, Ramat Gan, Israel. EM Yuval.Harpaz@biu.ac.il OI Harpaz, Yuval/0000-0002-3372-3630; Goldstein, Abraham/0000-0002-9349-0621 NR 19 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 1388-2457 EI 1872-8952 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD MAY PY 2015 VL 126 IS 5 BP 889 EP 897 DI 10.1016/j.clinph.2014.09.002 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CF0KT UT WOS:000352233500008 PM 25281474 ER PT J AU Ewen, JB Lakshmanan, BM Hallett, M Mostofsky, SH Crone, NE Korzeniewska, A AF Ewen, Joshua B. Lakshmanan, Balaji M. Hallett, Mark Mostofsky, Stewart H. Crone, Nathan E. Korzeniewska, Anna TI Dynamics of functional and effective connectivity within human cortical motor control networks SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EEG; Effective connectivity; Efference copy; Praxis ID CENTRAL EXECUTIVE FUNCTIONS; EVENT-RELATED CAUSALITY; PRAXIS HAND MOVEMENTS; THETA-OSCILLATIONS; WORKING-MEMORY; GAMMA OSCILLATIONS; IDEOMOTOR APRAXIA; INFORMATION-FLOW; BRAIN STRUCTURES; PREMOTOR AREAS AB Objective: Praxis, the performance of complex motor gestures, is crucial to the development of motor and social/communicative capacities. Praxis relies on a network consisting of inferior parietal and premotor regions, particularly on the left, and is thought to require transformation of spatio-temporal representations (parietal) into movement sequences (premotor). Method: We examined praxis network dynamics by measuring EEG effective connectivity while healthy subjects performed a praxis task. Results: Propagation from parietal to frontal regions was not statistically greater on the left than the right. However, propagation from left parietal regions to all other regions was significantly greater during gesture preparation than execution. Moreover, during gesture preparation only, propagation from the left parietal region to bilateral frontal regions was greater than reciprocal propagations to the left parietal region. This directional specificity was not observed for the right parietal region. Conclusions: These findings represent direct electrophysiological evidence for directionally predominant propagation in left frontal-parietal networks during praxis behavior, which may reflect neural mechanisms by which representations in the human brain select appropriate motor sequences for subsequent execution. Significance: In addition to bolstering the classic view of praxis network function, these results also demonstrate the relevance of additional information provided by directed connectivity measures. (C) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Ewen, Joshua B.; Lakshmanan, Balaji M.] Kennedy Krieger Inst, Dept Neurol & Dev Med, Baltimore, MD 21205 USA. [Ewen, Joshua B.; Mostofsky, Stewart H.; Crone, Nathan E.; Korzeniewska, Anna] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Mostofsky, Stewart H.] Kennedy Krieger Inst, Lab Neurocognit & Imaging Res, Baltimore, MD 21205 USA. [Mostofsky, Stewart H.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. RP Ewen, JB (reprint author), Kennedy Krieger Inst, Dept Neurol & Dev Med, 707 N Broadway, Baltimore, MD 21205 USA. EM ewen@kennedykrieger.org; lakshmanan@kennedykrieger.org; hallettm@ninds.nih.gov; mostofsky@kennedykrieger.org; ncrone@jhmi.edu; akorzen@jhmi.edu OI Ewen, Joshua/0000-0002-9203-9564 FU National Institutes of Neurological Disorders and Stroke at the National Institutes of Health [K23 NS073626, R01 NS048527, R01 NS40596]; Autism Speaks; NINDS FX This work was supported by the National Institutes of Neurological Disorders and Stroke at the National Institutes of Health (grant numbers K23 NS073626 to J.B.E., R01 NS048527 to S.H.M., and R01 NS40596 to N.E.C.; Intramural Program to M.H.) and Autism Speaks (to S.H.M.). Dr. Hallett is supported by the NINDS Intramural Program. The study sponsors had no role in collection, analysis or interpretation, or in the preparation of the manuscript. NR 54 TC 3 Z9 3 U1 1 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 EI 1872-8952 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD MAY PY 2015 VL 126 IS 5 BP 987 EP 996 DI 10.1016/j.clinph.2014.09.006 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CF0KT UT WOS:000352233500020 PM 25270239 ER PT J AU Whitworth, KW Baird, DD Steiner, AZ Bornman, RMS Travlos, GS Wilson, RE Longnecker, MP AF Whitworth, Kristina W. Baird, Donna D. Steiner, Anne Z. Bornman, Riana M. S. Travlos, Gregory S. Wilson, Ralph E. Longnecker, Matthew P. TI Anti-Mullerian Hormone and Lifestyle, Reproductive, and Environmental Factors Among Women in Rural South Africa SO EPIDEMIOLOGY LA English DT Article ID INHIBITING SUBSTANCE; OVARIAN RESERVE; SERUM-LEVELS; MARKER; HEALTH; ORGANOPHOSPHORUS; INSECTICIDES; FOLLICLES; ADULTHOOD; HISTORY AB Background: Few data exist regarding anti-Mullerian hormone, a marker of ovarian reserve, in relation to environmental factors with potential ovarian toxicity. Methods: This analysis included 420 women from Limpopo, South Africa studied in 2010-2011. Women were administered comprehensive questionnaires, and plasma concentrations of anti-Mullerian hormone and dichlorodiphenyltrichloroethane were determined. We used separate multivariable models to examine the associations between natural log-transformed anti-Mullerian hormone concentration (ng/ml) and each of the lifestyle, reproductive, and environmental factors of interest, adjusted for age, body mass index, education, and parity. Results: The median age of women was 24 years (interquartile range [IQR] - 22 to 26); the median anti-Mullerian hormone concentration was 3.1 ng/ml (IQR - 2.0 to 6.0). Women who reported indoor residual spraying in homes with painted walls (indicative of exposure to pyrethroids) had 25% lower (95% confidence interval [CI] = -39%, -8%) anti-Mullerian hormone concentrations compared with women who reported no spraying. Little evidence of decreased anti-Mullerian hormone concentrations was observed among women with the highest dichlorodiphenyltrichloroethane levels. Compared with women who used an electric stove, no association was observed among women who cooked indoors over open wood fires. The findings also suggested lower anti-Mullerian hormone concentrations among women who drank coffee (-19% [95% CI = -31%, -5%]) or alcohol (-21% [95% CI = -36%, -3%]). Conclusions: These are among the first data regarding anti-Mullerian hormone concentrations relative to pesticides and indoor air pollution. Our results are suggestive of decreased ovarian reserve associated with exposure to pyrethroid pesticides, which is consistent with laboratory animal data. C1 [Whitworth, Kristina W.] Univ Texas Sch Publ Hlth, San Antonio, TX 77030 USA. [Baird, Donna D.; Longnecker, Matthew P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Travlos, Gregory S.; Wilson, Ralph E.] NIEHS, Cellular & Mol Pathol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Steiner, Anne Z.] Univ N Carolina, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Chapel Hill, NC USA. [Bornman, Riana M. S.] Univ Pretoria, Dept Urol, Pretoria, South Africa. [Bornman, Riana M. S.] Univ Pretoria, Ctr Sustainable Malaria Control, ZA-0002 Pretoria, South Africa. RP Whitworth, KW (reprint author), Univ Texas Sch Publ Hlth, San Antonio Reg Campus, San Antonio, TX 77030 USA. EM Kristina.W.Whitworth@uth.tmc.edu RI Baird, Donna/D-5214-2017; OI Baird, Donna/0000-0002-5544-2653; Longnecker, Matthew/0000-0001-6073-5322 FU National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS) FX This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS). NR 38 TC 8 Z9 8 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1044-3983 EI 1531-5487 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2015 VL 26 IS 3 BP 429 EP 435 DI 10.1097/EDE.0000000000000265 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CF4BA UT WOS:000352492200025 PM 25710247 ER PT J AU Metcalf, CJE Tatem, A Bjornstad, ON Lessler, J O'Reilly, K Takahashi, S Cutts, F Grenfell, BT AF Metcalf, C. J. E. Tatem, A. Bjornstad, O. N. Lessler, J. O'Reilly, K. Takahashi, S. Cutts, F. Grenfell, B. T. TI Transport networks and inequities in vaccination: remoteness shapes measles vaccine coverage and prospects for elimination across Africa SO EPIDEMIOLOGY AND INFECTION LA English DT Article DE Epidemiology; modelling; measles (rubeola); rubella; vaccine policy development ID RUBELLA VACCINATION; UNITED-STATES; COUNTRIES; IMPACT; IMMUNIZATION; NIGERIA; EQUITY; RISK; SIZE; CHAD AB Measles vaccination is estimated to have averted 13.8 million deaths between 2000 and 2012. Persisting heterogeneity in coverage is a major contributor to continued measles mortality, and a barrier to measles elimination and introduction of rubella-containing vaccine. Our objective is to identify determinants of inequities in coverage, and how vaccine delivery must change to achieve elimination goals, which is a focus of the WHO Decade of Vaccines. We combined estimates of travel time to the nearest urban centre (>= 50 000 people) with vaccination data from Demographic Health Surveys to assess how remoteness affects coverage in 26 African countries. Building on a statistical mapping of coverage against age and geographical isolation, we quantified how modifying the rate and age range of vaccine delivery affects national coverage. Our scenario analysis considers increasing the rate of delivery of routine vaccination, increasing the target age range of routine vaccination, and enhanced delivery to remote areas. Geographical isolation plays a key role in defining vaccine inequity, with greater inequity in countries with lower measles vaccine coverage. Eliminating geographical inequities alone will not achieve thresholds for herd immunity, indicating that changes in delivery rate or age range of routine vaccination will be required. Measles vaccine coverage remains far below targets for herd immunity in many countries on the African continent and is likely to be inadequate for achieving rubella elimination. The impact of strategies such as increasing the upper age range eligible for routine vaccination should be considered. C1 [Metcalf, C. J. E.] Univ Oxford, Dept Zool, Oxford, England. [Metcalf, C. J. E.; Tatem, A.; Grenfell, B. T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Metcalf, C. J. E.; Takahashi, S.; Grenfell, B. T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Tatem, A.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England. [Tatem, A.] Flowminder Fdn, Stockholm, Sweden. [Bjornstad, O. N.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Lessler, J.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [O'Reilly, K.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Infect Dis Epidemiol, Med Res Council Ctr Outbreak Anal & Modelling, London, England. [Cutts, F.] London Sch Hyg & Trop Med, London WC1, England. RP Metcalf, CJE (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Eno Hall, Princeton, NJ 08544 USA. EM cmetcalf@princeton.edu OI Lessler, Justin/0000-0002-9741-8109; O'Reilly, Kathleen/0000-0002-4892-8022 FU Royal Society; Oxford University; Bill and Melinda Gates Foundation; Science and Technology Directorate, Department of Homeland Security [HSHQDC-12-C-00058]; RAPIDD program of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; Medical Research Council, UK FX This work is funded by the Royal Society and Oxford University (C.J.E.M.), the Bill and Melinda Gates Foundation, the Science and Technology Directorate, Department of Homeland Security contract HSHQDC-12-C-00058 (B.T.G.), and the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security and the Fogarty International Center, National Institutes of Health (C.J.E.M., B.T.G., O.N.B., A.J.T.), and the Medical Research Council, UK (K.O'R.). The funding sources played no role in developing this paper and preparing it for submission. NR 47 TC 4 Z9 4 U1 3 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 EI 1469-4409 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD MAY PY 2015 VL 143 IS 7 BP 1457 EP 1466 DI 10.1017/S0950268814001988 PG 10 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CF6ZW UT WOS:000352706700014 PM 25119237 ER PT J AU Greten, TF Wang, XW Korangy, F AF Greten, Tim F. Wang, Xin W. Korangy, Firouzeh TI Current concepts of immune based treatments for patients with HCC: from basic science to novel treatment approaches SO GUT LA English DT Article ID HEPATOCELLULAR-CARCINOMA PATIENTS; REGULATORY T-CELLS; LIVER-CANCER; RADIOFREQUENCY ABLATION; ANTITUMOR IMMUNITY; SUPPRESSOR-CELLS; DENDRITIC CELLS; CLINICAL-TRIAL; RESPONSES; SORAFENIB AB The recent approval of two immune checkpoint inhibitors for the treatment of malignant melanoma has sparked great interest by physicians and basic scientists searching for novel therapeutics for GI cancer. Chronic inflammation is recognised as a major risk factor for the development of hepatocellular carcinoma (HCC) and makes this type of cancer a potentially ideal target for an immune based treatment approach. Further evidence for a critical role of immune responses in patients with HCC is derived from the fact that immune signatures and profiles predict patients' outcome as well as the fact that tumour-induced spontaneous antitumour immunity can be detected. In addition ablative therapies can lead to changes in the number, phenotype and function of different immune cell subsets, which correlate with patients' survival. Various HCC-specific mouse models have been developed, which improve our understanding of hepatocarcinogenesis and tumour-immune cell interactions, and lead to the development of novel immune based treatment approaches, which are currently being evaluated in preclinical and in early clinical settings. Immune checkpoint blockade along with adoptive immune cell therapy and vaccine approaches are currently being evaluated either alone or in combination with other treatments. Here, we provide an overview for the rationale of immunotherapy in HCC, summarise ongoing studies and provide a perspective for immune based approaches in patients with HCC. C1 [Greten, Tim F.; Korangy, Firouzeh] NCI, Gastrointestinal Malignancy Sect, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Wang, Xin W.] NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Greten, TF (reprint author), NCI, Gastrointestinal Malignancy Sect, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, NIH NCI CCR Bldg 10 Rm 12N226, Bethesda, MD 20892 USA. EM tim.greten@nih.gov RI Wang, Xin/B-6162-2009 FU Intramural Research Program of the NCI, NIH FX This work was supported by the Intramural Research Program of the NCI, NIH. NR 111 TC 14 Z9 17 U1 1 U2 18 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD MAY PY 2015 VL 64 IS 5 BP 842 EP 848 DI 10.1136/gutjnl-2014-307990 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CF1GD UT WOS:000352291200019 PM 25666193 ER PT J AU Wall, AM Mukandala, G Greig, NH O'Connor, JJ AF Wall, Audrey M. Mukandala, Gatambwa Greig, Nigel H. O'Connor, John J. TI Tumor Necrosis Factor-alpha Potentiates Long-Term Potentiation in the Rat Dentate Gyrus After Acute Hypoxia SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE tumor necrosis factor-alpha; interleukin-1 beta; long-term potentiation; dentate gyrus; hypoxia; high-frequency stimulation; theta burst stimulation; 3,6 '-dithiothalidomide; 1,6 '-dithiorevlimid; CNTO1081; prolyl hydroxylase inhibition ID ELEMENT-BINDING PROTEIN; GLIAL TNF-ALPHA; IN-VITRO; SYNAPTIC-TRANSMISSION; INTERMITTENT HYPOXIA; HIPPOCAMPAL SLICES; RECEPTOR TRAFFICKING; SYNTHESIS INHIBITOR; GLUTAMATE-RECEPTOR; INTERLEUKIN-1-BETA AB An inadequate supply of oxygen in the brain may lead to an inflammatory response through neuronal and glial cells that can result in neuronal damage. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that is released during acute hypoxia and can have neurotoxic or neuroprotective effects in the brain. Both TNF-alpha and interleukin-1 beta (IL-1 beta) have been shown by a number of research groups to alter synaptic scaling and also to inhibit long-term potentiation (LTP) in the hippocampus when induced by specific high-frequency stimulation (HFS) protocols. This study examines the effects of TNFa on synaptic transmission and plasticity in hippocampal slices after acute hypoxia using two HFS protocols. Field excitatory postsynaptic potentials were elicited in the medial perforant pathway of the dentate gyrus. Exogenous TNF-alpha (5 ng/ml) attenuated LTP induced by theta burst stimulation but had no effect on LTP induced by a more prolonged HFS. Pretreatment with lipopolysaccharide (100 ng/ml) or TNF-alpha but not IL-1 beta (4 ng/ml) prior to a 30-min hypoxic insult resulted in a significant enhancement of LTP post hypoxia when induced by the HFS. Anti-TNF, 3,60-dithiothalidomide (a TNF-alpha synthesis inhibitor), and SB203580 (a p38 MAPK inhibitor) significantly reduced this effect. These results indicate an important modulatory role for elevated TNF-alpha levels on LTP in the hippocampus after an acute hypoxic event. VC 2015 Wiley Periodicals, Inc. C1 [Wall, Audrey M.; Mukandala, Gatambwa; O'Connor, John J.] Univ Coll Dublin, UCD Sch Biomol & Biomed Sci, UCD Conway Inst Biomol & Biomed Res, Dublin 4, Ireland. [Greig, Nigel H.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP O'Connor, JJ (reprint author), Univ Coll Dublin, UCD Sch Biomol & Biomed Sci, UCD Conway Inst Biomol & Biomed Res, Dublin 4, Ireland. EM john.connor@ucd.ie FU Science Foundation Ireland (SFI) [09/RFP/NES2450]; Intramural Research Program, National Institute on Aging FX Contract grant sponsor: Science Foundation Ireland (SFI); Contract grant number: 09/RFP/NES2450 (to J.J.O.); Contract grant sponsor: Intramural Research Program, National Institute on Aging (to N.H.G.) NR 56 TC 6 Z9 6 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0360-4012 EI 1097-4547 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAY PY 2015 VL 93 IS 5 BP 815 EP 829 DI 10.1002/jnr.23540 PG 15 WC Neurosciences SC Neurosciences & Neurology GA CE9FE UT WOS:000352148600014 PM 25641742 ER PT J AU Nalwoga, A Cose, S Wakeham, K Miley, W Ndibazza, J Drakeley, C Elliott, A Whitby, D Newton, R AF Nalwoga, Angela Cose, Stephen Wakeham, Katie Miley, Wendell Ndibazza, Juliet Drakeley, Christopher Elliott, Alison Whitby, Denise Newton, Robert TI Association between malaria exposure and Kaposi's sarcoma-associated herpes virus seropositivity in Uganda SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Article DE Kaposi's sarcoma-associated herpes virus; malaria; Uganda ID PLASMODIUM-FALCIPARUM; DOUBLE-BLIND; CHILDREN; RISK; HUMAN-HERPESVIRUS-8; EPIDEMIOLOGY; TRANSMISSION; IMMUNIZATION; ANTIBODIES; INFECTION AB ObjectiveUnlike other herpes viruses, Kaposi's sarcoma-associated herpes virus (KSHV) is not ubiquitous worldwide and is most prevalent in sub-Saharan Africa. The reasons for this are unclear. As part of a wider investigation of factors that facilitate transmission in Uganda, a high prevalence country, we examined the association between antimalaria antibodies and seropositivity against KSHV. MethodsAntibodies against P.falciparum merozoite surface protein (PfMSP)-1, P.falciparum apical membrane antigen (PfAMA)-1 and KSHV antigens (ORF73 and K8.1) were measured in samples from 1164 mothers and 1227 children. ResultsKaposi's sarcoma-associated herpes virus seroprevalence was 69% among mothers and 15% children. Among mothers, KSHV seroprevalence increased with malaria antibody titres: from 60% to 82% and from 54% to 77%, comparing those with the lowest and highest titres for PfMSP-1 and PfAMA-1, respectively (P<0.0001). Among children, only antibodies to PfAMA-1 were significantly associated with KSHV seropositivity, (P<0.0001). In both mothers and children, anti-ORF73 antibodies were more strongly associated with malaria antibodies than anti-K8.1 antibodies. ConclusionThe association between malaria exposure and KSHV seropositivity suggests that malaria is a cofactor for KSHV infection or reactivation. C1 [Nalwoga, Angela; Cose, Stephen; Wakeham, Katie; Ndibazza, Juliet; Elliott, Alison; Newton, Robert] Uganda Virus Res Inst, Med Res Council, Entebbe, Uganda. [Cose, Stephen; Drakeley, Christopher; Elliott, Alison] London Sch Hyg & Trop Med, London WC1, England. [Wakeham, Katie] Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland. [Miley, Wendell; Whitby, Denise] Frederick Natl Lab Canc Res, Viral Oncol Sect, Frederick, MD USA. [Newton, Robert] Univ York, York YO10 5DD, N Yorkshire, England. [Newton, Robert] Int Agcy Res Canc, F-69372 Lyon, France. RP Nalwoga, A (reprint author), MRC UVRI Uganda Res Unit AIDS, POB 49, Entebbe, Uganda. EM Angela.nalwoga@mrcuganda.org OI Elliott, Alison/0000-0003-2818-9549; Cose, Stephen/0000-0002-5156-037X FU National Institute of Health; Wellcome Trust, United Kingdom FX We thank the Entebbe Mother and Baby Study participants for their cooperation and providing us with their samples to make this project possible. We would like to acknowledge the Co-Infection Studies Program team of MRC/UVRI Uganda Research Unit on AIDS, for their support in carrying out this project, and thank Prof. Jonathan Levin for his statistical support. We would like to acknowledge Ismail Sebina and Alison Rand for their support in carrying out KSHV serological assays and malaria serological assays respectively. This project was funded with federal funds from the National Institute of Health and the Wellcome Trust, United Kingdom. NR 35 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1360-2276 EI 1365-3156 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD MAY PY 2015 VL 20 IS 5 BP 665 EP 672 DI 10.1111/tmi.12464 PG 8 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CF4QG UT WOS:000352534600012 PM 25611008 ER PT J AU Pongpiachan, S Hattayanone, M Choochuay, C Mekmok, R Wuttijak, N Ketratanakul, A AF Pongpiachan, S. Hattayanone, M. Choochuay, C. Mekmok, R. Wuttijak, N. Ketratanakul, A. TI Enhanced PM10 bounded PAHs from shipping emissions SO ATMOSPHERIC ENVIRONMENT LA English DT Article DE Industrial estate; Mutagenicity; Polycyclic aromatic compounds; Vehicle emissions; Thailand ID POLYCYCLIC AROMATIC-HYDROCARBONS; AIRBORNE PARTICULATE MATTER; SOURCE IDENTIFICATION; VERTICAL-DISTRIBUTION; SOURCE APPORTIONMENT; MUTAGENIC-ACTIVITY; WOOD COMBUSTION; RISK-ASSESSMENT; CHINESE COAL; URBAN AIR AB Earlier studies have highlighted the importance of maritime transport as a main contributor of air pollutants in port area. The authors intended to investigate the effects of shipping emissions on the enhancement of PM10 bounded polycyclic aromatic hydrocarbons (PAHs) and mutagenic substances in an industrial area of Rayong province, Thailand. Daily PM10 speciation data across two air quality observatory sites in Thailand during 2010-2013 were collected. Diagnostic binary ratios of PAH congeners, analysis of variances (ANOVA), and principal component analysis (PCA) were employed to evaluate the enhanced genotoxicity of PM10 during the docking period. Significant increase of PAHs and mutagenic index (MI) of PM10 were observed during the docking period in both sampling sites. Although stationary sources like coal combustions from power plants and vehicular exhausts from motorway can play a great role in enhancing PAH concentrations, regulating shipping emissions from diesel engine in the port area like Rayong is predominantly crucial. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Pongpiachan, S.; Choochuay, C.] NIDA, Sch Social & Environm Dev, Ctr Res & Dev Disaster Prevent & Management, Bangkok 10240, Thailand. [Hattayanone, M.] Songkhla Rajabhat Univ, Fac Humanities & Social Sci, Songkhla 90000, Thailand. [Mekmok, R.; Wuttijak, N.; Ketratanakul, A.] IRPC PCL, Bangkok 10900, Thailand. RP Pongpiachan, S (reprint author), NIDA, Sch Social & Environm Dev, Ctr Res & Dev Disaster Prevent & Management, 118 Moo 3,Sereethai Rd, Bangkok 10240, Thailand. EM pongpiajun@gmail.com FU IRPC FX This work was performed with the approval of the National Institute of Development Administration (NIDA) and financial support from IRPC. The authors acknowledge the staff of the Faculty of Environmental Management, Prince of Songkla University, and Bara Scientific Co., Ltd. for their contributions to the laboratory work. NR 58 TC 6 Z9 6 U1 4 U2 33 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1352-2310 EI 1873-2844 J9 ATMOS ENVIRON JI Atmos. Environ. PD MAY PY 2015 VL 108 BP 13 EP 19 DI 10.1016/j.atmosenv.2015.02.072 PG 7 WC Environmental Sciences; Meteorology & Atmospheric Sciences SC Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences GA CE4OB UT WOS:000351808800002 ER PT J AU Lee, W Mun, S Kang, K Hennighausen, L Han, K AF Lee, Wooseok Mun, Seyoung Kang, Keunsoo Hennighausen, Lothar Han, Kyudong TI Genome-wide target site triplication of Alu elements in the human genome SO GENE LA English DT Article DE Target site; Alu; Mobile element; Retrotransposon; TSD-TSD recombination ID MEDIATED DELETION; INSERTION; EVOLUTION; DNA; RETROPOSONS; LINEAGE AB Alu elements are the most successful short interspersed elements in primate genomes and their retrotransposition is a major source of genomic expansion. Alu elements integrate into genomic regions through target-site primed reverse transcription, which generates target site duplications (TSDs). Unexpectedly, we have identified target site triplications (TSTs) at some lad, where two Alu elements in tandem share one direct repeat. Thus, the three copies of the repeat are present. We located 212 TST loci in the human genome and examined 25 putative human-specific TST loci using PCR validation. As a result, 12 human-specific TST loci were identified. These findings suggest that unequal homologous recombination between TSDs can lead to TST. Through this mechanism, the copy number of Alu elements could have increased in primate genomes without new Alu retrotransposition events. This study provides new insight into the augmentation of Alu elements in the primate genome. (C) 2015 Elsevier B.V. All rights reserved. C1 [Lee, Wooseok; Mun, Seyoung; Han, Kyudong] Dankook Univ, Dept Nanobiomed Sci, Cheonan 330714, South Korea. [Lee, Wooseok; Mun, Seyoung; Han, Kyudong] Dankook Univ, PLUS NBM Global Res Ctr Regenerat Med BK21, Cheonan 330714, South Korea. [Mun, Seyoung; Hennighausen, Lothar] NIDDK, NIH, Lab Genet & Physiol, Bethesda, MD 20892 USA. [Kang, Keunsoo] Dankook Univ, Dept Microbiol, Cheonan 330714, South Korea. [Han, Kyudong] DKU Theragen Inst NGS Anal DTiNa, Cheonan 330714, South Korea. RP Han, K (reprint author), Dankook Univ, Dept Nanobiomed Sci, Cheonan 330714, South Korea. EM jim97@dankook.ac.kr FU Dankook University FX The present research was conducted by the research fund of Dankook University (BK21 Plus) in 2014. NR 25 TC 1 Z9 1 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD MAY 1 PY 2015 VL 561 IS 2 BP 283 EP 291 DI 10.1016/j.gene.2015.02.052 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CE4LM UT WOS:000351802100014 PM 25701601 ER PT J AU Drozdovitch, V Brill, AB Callahan, RJ Clanton, JA DePietro, A Goldsmith, SJ Greenspan, BS Gross, MD Hays, MT Moore, SC Ponto, JA Shreeve, WW Melo, DR Linet, MS Simon, SL AF Drozdovitch, Vladimir Brill, Aaron B. Callahan, Ronald J. Clanton, Jeffrey A. DePietro, Allegra Goldsmith, Stanley J. Greenspan, Bennett S. Gross, Milton D. Hays, Marguerite T. Moore, Stephen C. Ponto, James A. Shreeve, Walton W. Melo, Dunstana R. Linet, Martha S. Simon, Steven L. TI USE OF RADIOPHARMACEUTICALS IN DIAGNOSTIC NUCLEAR MEDICINE IN THE UNITED STATES: 1960-2010 SO HEALTH PHYSICS LA English DT Article DE diagnostic imaging; nuclear medicine; radiation, medical; radiopharmaceuticals ID LOWER GASTROINTESTINAL HEMORRHAGE; RED-BLOOD-CELLS; IN-111 CAPROMAB PENDETIDE; RADIOLOGIC TECHNOLOGISTS; TC-99M PYROPHOSPHATE; COMPUTED-TOMOGRAPHY; PULMONARY EMBOLISM; TECHNETIUM TC-99M; PROSTATE-CANCER; SCANNING AGENT AB To reconstruct reliable nuclear medicine-related occupational radiation doses or doses received as patients from radiopharmaceuticals over the last five decades, the authors assessed which radiopharmaceuticals were used in different time periods, their relative frequency of use, and typical values of the administered activity. This paper presents data on the changing patterns of clinical use of radiopharmaceuticals and documents the range of activity administered to adult patients undergoing diagnostic nuclear medicine procedures in the U.S. between 1960 and 2010. Data are presented for 15 diagnostic imaging procedures that include thyroid scan and thyroid uptake; brain scan; brain blood flow; lung perfusion and ventilation; bone, liver, hepatobiliary, bone marrow, pancreas, and kidney scans; cardiac imaging procedures; tumor localization studies; localization of gastrointestinal bleeding; and non-imaging studies of blood volume and iron metabolism. Data on the relative use of radiopharmaceuticals were collected using key informant interviews and comprehensive literature reviews of typical administered activities of these diagnostic nuclear medicine studies. Responses of key informants on relative use of radiopharmaceuticals are in agreement with published literature. Results of this study will be used for retrospective reconstruction of occupational and personal medical radiation doses from diagnostic radiopharmaceuticals to members of the U.S. radiologic technologists' cohort and in reconstructing radiation doses from occupational or patient radiation exposures to other U.S. workers or patient populations. C1 [Drozdovitch, Vladimir; Linet, Martha S.; Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Brill, Aaron B.] Vanderbilt Univ, Radiol & Radiol Sci, Nashville, TN 37235 USA. [Callahan, Ronald J.; DePietro, Allegra] Massachusetts Gen Hosp, Boston, MA USA. [Clanton, Jeffrey A.] Vanderbilt Univ, Nashville, TN 37235 USA. [Goldsmith, Stanley J.] New York Presbyterian Hosp, Weill Cornell Med Ctr, New York, NY USA. [Greenspan, Bennett S.] Univ Missouri, Columbia Nucl Med Program, Columbia, MO USA. [Gross, Milton D.] Dept Vet Affairs Hlth Syst, Nucl Med & Radiat Serv, Ann Arbor, MI USA. [Hays, Marguerite T.] Dept Vet Affairs Hlth Syst, Palo Alto, CA USA. [Moore, Stephen C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ponto, James A.] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Shreeve, Walton W.] Vet Affairs Northport, Long Isl City, NY USA. [Melo, Dunstana R.] Lovelace Resp Res Inst, Ctr Countermeasures Radiat, Albuquerque, NM USA. RP Drozdovitch, V (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 9609 Med Ctr Dr,Room 7E548 MSC 9778, Bethesda, MD 20892 USA. EM drozdovv@mail.nih.gov FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics, NCI, NIH FX This study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, NCI, NIH. Special thanks to Fred A. Mettler Jr. (New Mexico VA Health Care System, Albuquerque, NM) for his participation in the survey and for comments on our manuscript. NR 126 TC 3 Z9 3 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD MAY PY 2015 VL 108 IS 5 BP 520 EP 537 DI 10.1097/HP.0000000000000261 PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA CE5PP UT WOS:000351887900005 PM 25811150 ER PT J AU Grant, EJ Ozasa, K Ban, N Gonzalez, AB Cologne, J Cullings, HM Doi, K Furukawa, K Imaoka, T Kodama, K Nakamura, N Niwa, O Preston, DL Rajaraman, P Sadakane, A Saigusa, S Sakata, R Sobue, T Sugiyama, H Ullrich, R Wakeford, R Yasumura, S Milder, CM Shore, RE AF Grant, E. J. Ozasa, K. Ban, N. de Gonzalez, A. Berrington Cologne, J. Cullings, H. M. Doi, K. Furukawa, K. Imaoka, T. Kodama, K. Nakamura, N. Niwa, O. Preston, D. L. Rajaraman, P. Sadakane, A. Saigusa, S. Sakata, R. Sobue, T. Sugiyama, H. Ullrich, R. Wakeford, R. Yasumura, S. Milder, C. M. Shore, R. E. TI A REPORT FROM THE 2013 INTERNATIONAL SYMPOSIUM: THE EVALUATION OF THE EFFECTS OF LOW-DOSE RADIATION EXPOSURE IN THE LIFE SPAN STUDY OF ATOMIC BOMB SURVIVORS AND OTHER SIMILAR STUDIES SO HEALTH PHYSICS LA English DT Article DE cancer; epidemiology; radiation damage; radiation risk ID NATURAL BACKGROUND-RADIATION; GENERALIZED LINEAR-MODELS; CHILDHOOD LEUKEMIA; CANCER AB The RERF International Low-Dose Symposium was held on 5-6 December 2013 at the RERF campus in Hiroshima, Japan, to discuss the issues facing the Life Span Study (LSS) and other low-dose studies. Topics included the current status of low-dose risk detection, strategies for low-dose epidemiological and statistical research, methods to improve communication between epidemiologists and biologists, and the current status of radiological studies and tools. Key points made by the participants included the necessity of pooling materials over multiple studies to gain greater insight where data from single studies are insufficient; generating models that reflect epidemiological, statistical, and biological principles simultaneously; understanding confounders and effect modifiers in the current data; and taking into consideration less studied factors such as the impact of dose rate. It is the hope of all participants that this symposium be used as a trigger for further studies, especially those using pooled data, in order to reach a greater understanding of the health effects of low-dose radiation. C1 [Grant, E. J.; Ozasa, K.; Cologne, J.; Cullings, H. M.; Furukawa, K.; Kodama, K.; Nakamura, N.; Niwa, O.; Sadakane, A.; Saigusa, S.; Sakata, R.; Sugiyama, H.; Ullrich, R.; Milder, C. M.; Shore, R. E.] Radiat Effects Res Fdn, Hiroshima 7320815, Japan. [Ban, N.] Tokyo Healthcare Univ, Tokyo, Japan. [de Gonzalez, A. Berrington; Rajaraman, P.] US Natl Canc Inst, Bethesda, MD USA. [Doi, K.; Imaoka, T.; Saigusa, S.] Natl Inst Radiol Sci, Chiba 260, Japan. [Niwa, O.; Yasumura, S.] Fukushima Med Univ, Fukushima, Japan. [Preston, D. L.] Hirosoft, Eureka, CA USA. [Sobue, T.] Osaka Univ, Osaka, Japan. [Wakeford, R.] Univ Manchester, Manchester, Lancs, England. RP Grant, EJ (reprint author), Radiat Effects Res Fdn, Minami Ku, 5-2 Hijiyama Koen, Hiroshima 7320815, Japan. EM egrant@rerf.or.jp RI Imaoka, Tatsuhiko/E-5134-2012; OI Imaoka, Tatsuhiko/0000-0003-1507-585X; Wakeford, Richard/0000-0002-2934-0987 FU Japanese Ministry of Health, Labour and Welfare (MHLW); MHLW; U.S. Department of Energy (USDOE); USDOE [DE-HS0000031]; RERF Research Protocol [1-75] FX This symposium was funded through a grant for international collaboration from the Japanese Ministry of Health, Labour and Welfare (MHLW). The Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan, is a public interest foundation funded by the MHLW and the U.S. Department of Energy (USDOE). RERF research is also funded in part through USDOE award DE-HS0000031 to the National Academy of Sciences. This publication was supported by RERF Research Protocol 1-75. The views of the authors do not necessarily reflect those of the two governments. NR 6 TC 0 Z9 0 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD MAY PY 2015 VL 108 IS 5 BP 551 EP 556 DI 10.1097/HP.0000000000000262 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA CE5PP UT WOS:000351887900008 PM 25811153 ER PT J AU Lindsey, EW MacKinnon-Lewis, C Frabutt, JM Chambers, JC AF Lindsey, Eric W. MacKinnon-Lewis, Carol Frabutt, James M. Chambers, Jessica Campbell TI Cognitive Attributions and Emotional Expectancies Predict Emotions in Mother-Adolescent Interactions SO JOURNAL OF EARLY ADOLESCENCE LA English DT Article DE mother-adolescent; emotional expectancies; hostile attributions; expression of emotion ID LONGITUDINAL EXAMINATION; AGGRESSIVE-BEHAVIOR; CHILD RELATIONSHIPS; FAMILY; CONFLICT; INTERVENTION; ASSOCIATIONS; ADJUSTMENT; FATHERS AB The purpose of this study was to examine adolescent's hostile attributions of mother's intent and emotional self-expectancies as contributors to expression of emotion between mothers and adolescents. Data were collected from 268 10- to 12-year-olds (133 girls, 135 boys) and their mothers. Each dyad was observed in a conversational activity that was coded for both partners' expressions of four discrete emotions: happiness, anger, sadness, and fear. Adolescents responded to hypothetical stories to assess their emotional expectancies and attributions. Regression analysis revealed that adolescents' hostile attributions and emotional expectancies made independent contributions to the expression of happiness and anger with their mother. Adolescents who interpreted their mother's hypothetical behavior as hostile, and who expected to feel less happiness and more anger in response to their mother's hypothetical behavior, expressed less happiness and more anger with their mother. The findings support the conceptual distinction between hostile attributions and emotional expectancies. C1 [Lindsey, Eric W.] Penn State Univ, Appl Psychol, Reading, PA 19610 USA. [MacKinnon-Lewis, Carol] Univ S Florida, Dept Child & Family Studies, Tampa, FL USA. [Frabutt, James M.] Univ Notre Dame, Notre Dame, IN 46556 USA. [Chambers, Jessica Campbell] NIDA, Div Clin Neurosci Dev & Behav Res, Bethesda, MD 20892 USA. RP Lindsey, EW (reprint author), Penn State Univ, Dept Appl Psychol, Berks Campus,Tulpehocken Rd,POB 7009, Reading, PA 19610 USA. EM EWL10@psu.edu FU William T. Grant Foundation [017396218] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by William T. Grant Foundation Grant 017396218. NR 37 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-4316 EI 1552-5449 J9 J EARLY ADOLESCENCE JI J. Early Adolesc. PD MAY PY 2015 VL 35 IS 4 BP 484 EP 510 DI 10.1177/0272431614540525 PG 27 WC Family Studies; Psychology, Developmental SC Family Studies; Psychology GA CE5DG UT WOS:000351849900003 ER PT J AU Jager, J Yuen, CX Putnick, DL Hendricks, C Bornstein, MH AF Jager, Justin Yuen, Cynthia X. Putnick, Diane L. Hendricks, Charlene Bornstein, Marc H. TI Adolescent-Peer Relationships, Separation and Detachment From Parents, and Internalizing and Externalizing Behaviors: Linkages and Interactions SO JOURNAL OF EARLY ADOLESCENCE LA English DT Article DE separation; detachment; internalizing; externalizing; latent variable interactions ID EMOTIONAL AUTONOMY SCALE; PSYCHOLOGICAL SEPARATION; PSYCHOSOCIAL ADJUSTMENT; SOCIOECONOMIC-STATUS; LATENT-VARIABLES; YOUNG ADULTHOOD; FAMILY-MEMBERS; WORKING MODELS; FIT INDEXES; ALCOHOL-USE AB Most research exploring the interplay between context and adolescent separation and detachment has focused on the family; in contrast, this investigation directs its attention outside of the family to peers. Utilizing a latent variable approach for modeling interactions and incorporating reports of behavioral adjustment from 14-year-old adolescents (N = 190) and their mothers, we examine how separation and detachment relate to adolescent-peer relationships, and whether peer relationships moderate how separation and detachment relate to adolescent internalizing and externalizing behaviors. Positive peer relationships were both associated with lower detachment and sharply attenuated relations between detachment and higher adolescent internalizing and externalizing. Separation from parents was unrelated to peer relationships, and regardless of whether peer relationships were positive, separation was not related to adolescent internalizing and externalizing. We integrate these findings with those from family-focused investigations and discuss their substantive and clinical implications. C1 [Jager, Justin] Arizona State Univ, T Denny Sanford Sch Social & Family Dynam, Tempe, AZ 85287 USA. [Yuen, Cynthia X.] Univ Illinois, Urbana, IL 61801 USA. [Putnick, Diane L.; Hendricks, Charlene] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res Sect, Bethesda, MD USA. [Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, Bethesda, MD USA. RP Jager, J (reprint author), Arizona State Univ, T Denny Sanford Sch Social & Family Dynam, POB 873701, Tempe, AZ 85287 USA. EM justin.jager@asu.edu OI Putnick, Diane/0000-0002-6323-749X FU Intramural Research Program of the NIH, NICHD FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Intramural Research Program of the NIH, NICHD. NR 72 TC 1 Z9 1 U1 6 U2 33 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-4316 EI 1552-5449 J9 J EARLY ADOLESCENCE JI J. Early Adolesc. PD MAY PY 2015 VL 35 IS 4 BP 511 EP 537 DI 10.1177/0272431614537116 PG 27 WC Family Studies; Psychology, Developmental SC Family Studies; Psychology GA CE5DG UT WOS:000351849900004 ER PT J AU Farhat, T Haynie, D Summersett-Ringgold, F Brooks-Russell, A Iannotti, RJ AF Farhat, Tilda Haynie, Denise Summersett-Ringgold, Faith Brooks-Russell, Ashley Iannotti, Ronald J. TI Weight Perceptions, Misperceptions, and Dating Violence Victimization Among US Adolescents SO JOURNAL OF INTERPERSONAL VIOLENCE LA English DT Article DE dating violence; adolescents; obesity; weight perceptions; gender ID HEALTH-RISK BEHAVIORS; BODY-MASS INDEX; ROMANTIC RELATIONSHIPS; RELATIONAL AGGRESSION; SEXUAL RELATIONSHIPS; PARTNER VIOLENCE; SUBSTANCE USE; OBESITY; PREVALENCE; CHILDREN AB Dating violence is a major public health issue among youth. Overweight/obese adolescents experience peer victimization and discrimination and may be at increased risk of dating violence victimization. Furthermore, given the stigma associated with overweight/obesity, perceptions and misperceptions of overweight may be more important than actual weight status for dating violence victimization. This study examines the association of three weight indices (weight status, perceived weight, and weight perception accuracy) with psychological and physical dating violence victimization. The 2010 baseline survey of the 7-year NEXT Generation Health Study used a three-stage stratified clustered sampling design to select a nationally representative sample of U.S. 10th-grade students (n = 1,983). Participants who have had a boyfriend/girlfriend reported dating violence victimization and perceived weight. Weight status was computed from measured height/weight. Weight perception accuracy (accurate/underestimate/overestimate) was calculated by comparing weight status and perceived weight. Gender-stratified regressions examined the association of weight indices and dating violence victimization. Racial/ethnic differences were also examined. The association of weight indices with dating violence victimization significantly differed by gender. Overall, among boys, no associations were observed. Among girls, weight status was not associated with dating violence victimization, nor with number of dating violence victimization acts; however, perceived weight and weight perception accuracy were significantly associated with dating violence victimization, type of victimization, and number of victimization acts. Post hoc analyses revealed significant racial/ethnic differences. White girls who perceive themselves (accurately or not) to be overweight, and Hispanic girls who are overweight, may be at increased risk of dating violence victimization. These findings suggest a targeted approach to dating violence victimization prevention. C1 [Farhat, Tilda] NCI, Ctr Reduce Canc Hlth Dispar, NIH, Bethesda, MD 20892 USA. [Haynie, Denise] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, NIH, Bethesda, MD USA. [Summersett-Ringgold, Faith; Brooks-Russell, Ashley; Iannotti, Ronald J.] NIH, Bethesda, MD 20892 USA. RP Farhat, T (reprint author), NCI, Dispar Res Branch, Ctr Reduce Canc Hlth Dispar, NIH, 9609 Med Ctr Dr,MSC 9746,Room 6W246, Bethesda, MD 20892 USA. EM Tilda.Farhat@nih.gov OI Haynie, Denise/0000-0002-8270-6079 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HHSN267200800009C]; National Heart, Lung and Blood Institute (NHLBI); National Institute on Alcohol Abuse and Alcoholism (NIAAA); Maternal and Child Health Bureau (MCHB) of the Health Resources and Services Administration (HRSA) FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project (contract number HHSN267200800009C) was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Heart, Lung and Blood Institute (NHLBI); the National Institute on Alcohol Abuse and Alcoholism (NIAAA); and Maternal and Child Health Bureau (MCHB) of the Health Resources and Services Administration (HRSA), with supplemental support from the National Institute on Drug Abuse (NIDA). NR 37 TC 3 Z9 3 U1 4 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0886-2605 EI 1552-6518 J9 J INTERPERS VIOLENCE JI J. Interpers. Violence PD MAY PY 2015 VL 30 IS 9 BP 1511 EP 1532 DI 10.1177/0886260514540804 PG 22 WC Criminology & Penology; Family Studies; Psychology, Applied SC Criminology & Penology; Family Studies; Psychology GA CE7FR UT WOS:000352003900004 PM 25001616 ER PT J AU John, WS Newman, AH Nader, MA AF John, William S. Newman, Amy Hauck Nader, Michael A. TI Differential effects of the dopamine D-3 receptor antagonist PG01037 on cocaine and methamphetamine self-administration in rhesus monkeys SO NEUROPHARMACOLOGY LA English DT Article DE Cocaine; Methamphetamine; Dopamine D-3 receptors; PG01037; Self-administration; Rhesus monkeys ID CUE-INDUCED REINSTATEMENT; DRUG-SEEKING BEHAVIOR; D3 RECEPTOR; DISCRIMINATIVE-STIMULUS; SQUIRREL-MONKEYS; AGONIST 7-OH-DPAT; NICOTINE-SEEKING; UP-REGULATION; MICE LACKING; RATS AB The dopamine D-3 receptor (D3R) has been shown to mediate many of the behavioral effects of psychostimulants associated with high abuse potential. This study extended the assessment of the highly selective D3R antagonist PG01037 on cocaine and methamphetamine (MA) self-administration to include a food-drug choice procedure. Eight male rhesus monkeys (n = 4/group) served as subjects in which complete cocaine and MA dose response curves were determined daily in each session. When choice was stable, monkeys received acute and five-day treatment of PG01037 (1.0-5.6 mg/kg, i.v.). Acute administration of PG01037 was effective in reallocating choice from cocaine to food and decreasing cocaine intake, however, tolerance developed by day 5 of treatment. Up to doses that disrupted responding, MA choice and intake were not affected by PG01037 treatment. PG01037 decreased total reinforcers earned per session and the behavioral potency was significantly greater on MA-food choice compared to cocaine-food choice. Furthermore, the acute efficacy of PG01037 was correlated with the sensitivity of the D-3/D2R agonist quinpirole to elicit yawning. These data suggest (1) that efficacy of D3R compounds in decreasing drug choice is greater in subjects with lower D3R, perhaps suggesting that it is percent occupancy that is the critical variable in determining efficacy and (2) differences in D3R activity in chronic cocaine vs. MA users. Although tolerance developed to the effects of PG01037 treatment on cocaine choice, tolerance did not develop to the disruptive effects on food-maintained responding. These findings suggest that combination treatments that decrease cocaine-induced elevations in DA may enhance the efficacy of D3R antagonists on cocaine self-administration. (C) 2015 Elsevier Ltd. All rights reserved. C1 [John, William S.; Nader, Michael A.] Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA. [Newman, Amy Hauck] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, Baltimore, MD USA. RP Nader, MA (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM wjohn@wakehealth.edu; anewman@intra.nida.nih.gov; mnader@wakehealth.edu FU National Institute on Drug Abuse [DA012460]; NIDA-IRP; [T32 AA-007565] FX We would like to thank Michelle Bell for excellent technical assistance working with the monkeys, J. Cao for the synthesis of PG01037 and Dr. Paul Czoty for statistical consultation. This research was supported by the National Institute on Drug Abuse grant DA012460 and NIDA-IRP. WS John is supported by T32 AA-007565. NR 73 TC 6 Z9 6 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD MAY PY 2015 VL 92 BP 34 EP 43 DI 10.1016/j.neuropharm.2014.12.024 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CE4IG UT WOS:000351793700005 PM 25576373 ER PT J AU Kolb, EA Sampson, V Stabley, D Walter, A Sol-Church, K Cripe, T Hingorani, P Ahern, CH Weigel, BJ Zwiebel, J Blaney, SM AF Kolb, E. . Anders Sampson, Valerie Stabley, Deborah Walter, Alexa Sol-Church, Katia Cripe, Timothy Hingorani, Pooja Ahern, Charlotte Hsieh Weigel, Brenda J. Zwiebel, James Blaney, Susan M. TI A Phase I Trial and Viral Clearance Study of Reovirus (Reolysin) in Children With Relapsed or Refractory Extracranial Solid Tumors: A Children's Oncology Group Phase I Consortium Report SO PEDIATRIC BLOOD & CANCER LA English DT Article DE phase 1; pediatric cancer; pirotherapy ID INTRAVENOUS ONCOLYTIC REOVIRUS; RECURRENT MALIGNANT GLIOMAS; ADVANCED CANCER; NEONATAL MICE; THERAPY; TYPE-3; INFECTION; CELLS; PREVALENCE; ANTIBODIES AB BackgroundReovirus is a naturally occurring human virus that is cytopathic to malignant cells possessing an activated Ras signaling pathway. We conducted a phase I trial of Reolysin, a manufactured, proprietary isolate of purified reovirus, in children with relapsed/refractory extracranial solid tumors to define the recommended phase 2 dose (RP2D), toxicities, and pharmacokinetic properties when administered as a single agent or in combination with cyclophosphamide. ProceduresReolysin was administered intravenously for 5 consecutive days, every 28 days. Using a 3+3 design, the following dose levels were evaluated: 3x10(8) Tissue Culture Inhibitory Dose 50% (TCID50)/kg; 5x10(8) TCID50/kg (maximum dose was 3x10(10) TCID50); and 5x10(8) TCID50/kg plus oral cyclophosphamide (50mg/m(2)/day x 21 days). ResultsTwenty-nine patients were enrolled; 28 were eligible and 24 were evaluable for toxicity and response. There were no hematologic dose-limiting toxicities. Grade 5 respiratory failure and a Grade 5 thromboembolic event were reported, both in the setting of progressive disease. The median time to clear the reovirus viremia was 6.5 days. Eight of 24 patients were viremic beyond the 5 days of therapy, all were negative by day 17. No patient had detectable viral RNA in saliva or stool. There were no objective responses. ConclusionsReolysin at a dose of 5x10(8) TCID50/kg daily for 5 days was well tolerated in children alone and in combination with oral cyclophosphamide. Virus was cleared rapidly from the serum and shedding in stool and saliva was not detectable. Pediatr Blood Cancer 2015;62:751-758. (c) 2015 Wiley Periodicals, Inc. C1 [Kolb, E. . Anders; Sampson, Valerie; Walter, Alexa] Nemours AI duPont Jospital Children, Nemours Ctr Canc & Blood Disorders, Wilmington, DE USA. [Stabley, Deborah; Sol-Church, Katia] Nemours AI duPont Jospital Children, Nemours Biomol Core Lab, Wilmington, DE USA. [Cripe, Timothy] Ohio State Univ, Nationwide Childrens Hosp, Div Hematol Oncol BMT, Columbus, OH 43210 USA. [Hingorani, Pooja] Phoenix Childrens Hosp, Div Hematol & Oncol, Phoenix, AZ USA. [Ahern, Charlotte Hsieh] Baylor Coll Med, Dept Med, Div Biostat, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Weigel, Brenda J.] Univ Minnesota, Amplatz Childrens Hosp, Div Hematol & Oncol, Minneapolis, MN USA. [Zwiebel, James] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Blaney, Susan M.] Baylor Coll Med, Texas Childrens Canc Ctr, Div Hematol Oncol, Dept Med, Houston, TX 77030 USA. RP Kolb, EA (reprint author), Alfred I DuPont Hosp Children, Nemours Ctr Canc & Blood Disorders, 1600 Rockland Rd, Wilmington, DE 19803 USA. EM eakolb@nemours.org FU National Institute of General Medical Sciences of the National Institutes of Health [P20GM103464, P20GM103446]; NIH Pediatric Phase 1/Pilot Consortium [5UM1 CA097452-12] FX Grant sponsor: National Institute of General Medical Sciences of the National Institutes of Health; Grant numbers: P20GM103464; P20GM103446; Grant sponsor: NIH Pediatric Phase 1/Pilot Consortium; Grant number: 5UM1 CA097452-12 NR 39 TC 6 Z9 6 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2015 VL 62 IS 5 BP 751 EP 758 DI 10.1002/pbc.25464 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CE2WC UT WOS:000351680400005 PM 25728527 ER PT J AU Estrada-Veras, J Alvarado-Enriquez, J O'Brien, K Gahl, W AF Estrada-Veras, Juvianee Alvarado-Enriquez, Jhonell O'Brien, Kevin Gahl, William TI ERDHEIM CHESTER DISEASE: CLINICAL CHARACTERISTICS OF 40 CASES SEEN AT THE NIH CLINICAL CENTER SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Estrada-Veras, Juvianee; Alvarado-Enriquez, Jhonell; O'Brien, Kevin; Gahl, William] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2015 VL 62 SU 1 BP S8 EP S8 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CE2VZ UT WOS:000351680100034 ER PT J AU Sieni, E Tesi, B Romano, F Ciambotti, B Neves, C Chiang, S Galli, L Avenali, S Tondo, A Cordeiro, AI Schlums, H Jan-Inge-Henter Canessa, C Lippi, F Nordenskjold, M Hsu, A Holland, SM Neves, JF Azzari, C Bryceson, Y AF Sieni, Elena Tesi, Bianca Romano, Francesca Ciambotti, Benedetta Neves, Conceicao Chiang, Samuel Galli, Luisa Avenali, Stefano Tondo, Annalisa Cordeiro, Ana Isabel Schlums, Heinrich Jan-Inge-Henter Canessa, Clementina Lippi, Francesca Nordenskjold, Magnus Hsu, Amy Holland, Steven M. Neves, Joao Farelas Azzari, Chiara Bryceson, Yenan TI INTERFERON (IFN)-gamma RECEPTOR DEFICIENCY PRESENTING AS FATAL HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH): REPORT OF TWO CASES SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Sieni, Elena; Ciambotti, Benedetta; Tondo, Annalisa] Anna Meyer Childrens Univ Hosp, Dept Pediat Hematol Oncol, Florence, Italy. [Tesi, Bianca; Jan-Inge-Henter] Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Karolinska Univ Hosp Solna, Stockholm, Sweden. [Tesi, Bianca; Nordenskjold, Magnus] Karolinska Inst, Clin Genet Unit, Dept Mol Med & Surg, Karolinska Univ Hosp, Stockholm, Sweden. [Tesi, Bianca; Nordenskjold, Magnus] Karolinska Inst, Ctr Mol Med, Karolinska Univ Hosp, Stockholm, Sweden. [Romano, Francesca; Canessa, Clementina; Lippi, Francesca; Azzari, Chiara] Univ Florence, Dept Hlth Sci, Div Pediat Immunol, Florence, Italy. [Romano, Francesca; Galli, Luisa; Canessa, Clementina; Lippi, Francesca; Azzari, Chiara] Anna Meyer Childrens Hosp, Florence, Italy. [Neves, Conceicao; Cordeiro, Ana Isabel; Neves, Joao Farelas] Pediat Univ Hosp, Hosp Dona Estefania, Primary Immunodeficiencies Unit, Lisbon, Portugal. [Chiang, Samuel; Schlums, Heinrich; Bryceson, Yenan] Karolinska Inst, Karolinska Univ Hosp Huddinge, Dept Med, Ctr Infect Med, Stockholm, Sweden. [Galli, Luisa] Univ Florence, Dept Hlth Sci, Div Pediat Infect Dis, Florence, Italy. [Avenali, Stefano] Anna Meyer Childrens Univ Hosp, Dept Pediat Anesthesia & Intens Care, Florence, Italy. [Hsu, Amy; Holland, Steven M.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2015 VL 62 SU 1 BP S15 EP S15 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CE2VZ UT WOS:000351680100062 ER PT J AU Mattoo, TK Carpenter, MA Moxey-Mims, M Chesney, RW AF Mattoo, Tej K. Carpenter, Myra A. Moxey-Mims, Marva Chesney, Russell W. CA RIVUR Trial Investigators TI The RIVUR trial: a factual interpretation of our data SO PEDIATRIC NEPHROLOGY LA English DT Editorial Material DE Vesicoureteral reflux; Urinary tract infection; Children; Antimicrobial prophylaxis; Prospective trials; Renal scarring ID URINARY-TRACT-INFECTION; VESICOURETERAL REFLUX; ANTIBIOTIC-PROPHYLAXIS; CHILDREN; PYELONEPHRITIS; MULTICENTER; GUIDELINES AB Vesicoureteral reflux (VUR) increases the risk of urinary tract infection (UTI) and renal scarring. Many prospective studies have evaluated the role of antimicrobial prophylaxis in the prevention of recurrent UTI and renal scarring in children with VUR. Of these, the RIVUR trial was the largest, randomized, placebo-controlled, double blind, multicenter study, involving 607 children aged 2-72 months with grade I-IV VUR and a first or second symptomatic UTI. The median age of children in the RIVUR trial was 12 months, 92 % were female, 91 % were randomized after a first UTI, 86 % had a febrile index UTI, and 71 (56 %) of 126 toilet-trained children had bladder bowel dysfunction. Trimethoprim/sulfamethoxazole reduced the risk of UTI recurrences by 50 % (hazard ratio 0.50; 95 % confidence interval 0.34-0.74) as compared to placebo. No significant difference was seen in renal scarring between the two groups. However, this does not invalidate the role of prophylaxis in preventing renal scars because RIVUR and other recent prospective studies were not designed to address renal scarring as a primary study endpoint. In view of the RIVUR Trial and other studies that showed similar results, albeit in selected groups of patients, the debate on antimicrobial prophylaxis should shift from "no prophylaxis" to "selective prophylaxis" in children with VUR. C1 [Mattoo, Tej K.] Wayne State Univ, Sch Med, Childrens Hosp Michigan, Div Pediat Nephrol & Hypertens, Detroit, MI 48201 USA. [Carpenter, Myra A.] Univ N Carolina, Chapel Hill, NC USA. [Moxey-Mims, Marva] NIDDK, Bethesda, MD 20892 USA. [Chesney, Russell W.] Le Bonheur Childrens Hosp, Memphis, TN USA. RP Mattoo, TK (reprint author), Wayne State Univ, Sch Med, Childrens Hosp Michigan, Div Pediat Nephrol & Hypertens, 3901 Beaubien Blvd, Detroit, MI 48201 USA. EM tmattoo@med.wayne.edu FU NIDDK NIH HHS [U01 DK074062] NR 17 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0931-041X EI 1432-198X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD MAY PY 2015 VL 30 IS 5 BP 707 EP 712 DI 10.1007/s00467-014-3022-1 PG 6 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA CE3DY UT WOS:000351706700003 PM 25558811 ER PT J AU Lee, JW Huang, JD Rodriguez, IR AF Lee, Jung Wha Huang, Jiahn-Dar Rodriguez, Ignacio R. TI Extra-hepatic metabolism of 7-ketocholesterol occurs by esterification to fatty acids via cPLA2 alpha and SOAT1 followed by selective efflux to HDL SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Article DE 7-Ketocholesterol; 7-Ketocholesterol fatty acid ester; SOAT1; cPLA2 alpha; HDL; Cultured RPE cell ID CHOLESTEROL 7-ALPHA-HYDROXYLASE; HEPATIC-METABOLISM; OXYSTEROL; MICE; SULFOTRANSFERASE; EXPRESSION; CELLS; LIVER; ACYLTRANSFERASE; LOCALIZATION AB Accumulation of 7-ketocholesterol (7KCh) in tissues has been previously associated with various chronic aging diseases. Orally ingested 7KCh is readily metabolized by the liver and does not pose a toxicity threat. However, 7KCh formed in situ, usually associated with lipoprotein deposits, can adversely affect surrounding tissues by causing inflammation and cytotoxicity. In this study we have investigated various mechanisms for extrahepatic metabolism of 7KCh (e.g. hydroxylation, sulfation) and found only esterification to fatty acids. The esterification of 7KCh to fatty acids involves the combined action of cytosolic phospholipase A2 alpha (cPLA2 alpha) and sterol O-acyltransferase (SOAT1). Inhibition of either one of these enzymes ablates 7KCh-fatty acid ester (7KFAE) formation. The 7KFAEs are not toxic and do not induce inflammatory responses. However, they can be unstable and re-release 7KCh. The higher the degree of unsaturation, the more unstable the 7KFAE (e.g. 18:0 > 18:1 > 18:2 >> 18:3 20:4). Biochemical inhibition and siRNA knockdown of SOAT1 and cPLA2a ablated the 7KFAE synthesis in cultured ARPE19 cells, but had little effect on the 7KCh-induced inflammatory response. Overexpression of SOAT1 reduced the 7KCh-induced inflammatory response and provided some protection from cell death. This effect is likely due to the increased conversion of 7KCh to 7KFAEs, which reduced the intracellular 7KCh levels. Addition of HDL selectively increased the efflux of 7KFAEs and enhanced the effect of SOAT1 overexpression. Our data suggests an additional function for HDL in aiding extra-hepatic tissues to eliminate 7KCh by returning 7KFAEs to the liver for bile acid formation. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Lee, Jung Wha; Huang, Jiahn-Dar; Rodriguez, Ignacio R.] NEI, NIH, LRCMB, Mech Retinal Dis Sect, Bethesda, MD 20892 USA. RP Lee, JW (reprint author), NEI, NIH, LRCMB, Mech Retinal Dis Sect, 6 Ctr Dr,MSC0608,Bldg 6 Rm 131, Bethesda, MD 20892 USA. EM leej@nei.nih.gov FU National Eye Institute Intramural Research Program FX This work was supported by the National Eye Institute Intramural Research Program. NR 33 TC 0 Z9 0 U1 1 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 EI 0006-3002 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD MAY PY 2015 VL 1851 IS 5 BP 605 EP 619 DI 10.1016/j.bbalip.2015.01.007 PG 15 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CE4LF UT WOS:000351801400009 PM 25617738 ER PT J AU Konig, G Brooks, BR AF Koenig, Gerhard Brooks, Bernard R. TI Correcting for the free energy costs of bond or angle constraints in molecular dynamics simulations SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE Free energy calculation; Constraint correction; Molecular dynamics simulation; Normal mode analysis; Bennett's acceptance ratio ID BENNETTS ACCEPTANCE RATIO; AQUEOUS-SOLUTION; STATISTICAL-MECHANICS; FORCE-FIELD; CHARMM; TERMS; MACROMOLECULES; SOLVATION; HYDRATION; MODELS AB Background: Free energy simulations are an important tool in the arsenal of computational biophysics, allowing the calculation of thermodynamic properties of binding or enzymatic reactions. This paper introduces methods to increase the accuracy and precision of free energy calculations by calculating the free energy costs of constraints during post-processing. The primary purpose of employing constraints for these free energy methods is to increase the phase space overlap between ensembles, which is required for accuracy and convergence. Methods: The free energy costs of applying or removing constraints are calculated as additional explicit steps in the free energy cycle. The new techniques focus on hard degrees of freedom and use both gradients and Hessian estimation. Enthalpy, vibrational entropy, and Jacobian free energy terms are considered. Results: We demonstrate the utility of this method with simple classical systems involving harmonic and anharmonic oscillators, four-atomic benchmark systems, an alchemical mutation of ethane to methanol, and free energy simulations between alanine and serine. The errors for the analytical test cases are all below 0.0007 kcal/mol, and the accuracy of the free energy results of ethane to methanol is improved from 0.15 to 0.04 kcal/mol. For the alanine to serine case, the phase space overlaps of the unconstrained simulations range between 0.15 and 0.9%. The introduction of constraints increases the overlap up to 2.05%. On average, the overlap increases by 94% relative to the unconstrained value and precision is doubled. Conclusions: The approach reduces errors arising from constraints by about an order of magnitude. Free energy simulations benefit from the use of constraints through enhanced convergence and higher precision. General significance: The primary utility of this approach is to calculate free energies for systems with disparate energy surfaces and bonded terms, especially in multi-scale molecular mechanics/quantum mechanics simulations. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Published by Elsevier B.V. C1 [Koenig, Gerhard; Brooks, Bernard R.] NHLBI, NIH, Lab Computat Biol, Rockville, MD 20852 USA. RP Konig, G (reprint author), NHLBI, NIH, Lab Computat Biol, 5635 Fishers Lane T-900 Suite, Rockville, MD 20852 USA. EM gerhard.koenig@nih.gov FU National Heart, Lung and Blood Institute of the National Institutes of Health FX The authors would like to thank Tim Miller, Stefan Boresch, Yihan Shao, Alex Sodt and Lee Woodcock for insightful discussions, as well as Frank Pickard and Noreen Gervasi for critically reading the manuscript. This work was supported by the intramural research program of the National Heart, Lung and Blood Institute of the National Institutes of Health and utilized the high-performance computational capabilities of the LoBoS and Biowulf Linux clusters at the National Institutes of Health. (http://www.lobos.nih.gov/ and http://biowulf.nih.gov). NR 70 TC 14 Z9 14 U1 3 U2 41 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 EI 1872-8006 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD MAY PY 2015 VL 1850 IS 5 SI SI BP 932 EP 943 DI 10.1016/j.bbagen.2014.09.001 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CC9QW UT WOS:000350706700009 PM 25218695 ER PT J AU Karyadi, DM Zhao, SS He, QC McIntosh, L Wright, JL Ostrander, EA Feng, ZD Stanford, JL AF Karyadi, Danielle M. Zhao, Shanshan He, Qianchuan McIntosh, Laura Wright, Jonathan L. Ostrander, Elaine A. Feng, Ziding Stanford, Janet L. TI Confirmation of genetic variants associated with lethal prostate cancer in a cohort of men from hereditary prostate cancer families SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE AKT1; hereditary prostate cancer; mortality; SNPs; XRCC1; RNASEL ID RNASEL; MECHANISMS; PATHWAYS; LINKAGE; TRENDS; RISK AB Germline genetic variants have been suggested as prognostic biomarkers for identifying patients at high risk for lethal prostate cancer (PCa). Validation studies have confirmed the association of several single nucleotide polymorphisms (SNPs) with fatal PCa, but whether these variants affect PCa-specific mortality (PCSM) in patients with an inherited predisposition to PCa, based on familial history, is unknown. For this study, a cohort of 957 PCa patients from 270 hereditary prostate cancer families of European ancestry was genotyped for a panel of 22 PCSM-associated SNPs. Death certificates were reviewed to confirm cause of death. Mixed-effect Cox proportional hazards models were used to assess survival according to genotypes, accounting for relatedness and clinicopathological factors. Within this cohort, 98 PCa deaths were confirmed over an average follow-up period of 12.7 years after diagnosis. Variant allele carriers for three SNPs had significantly altered risk for PCSM [rs635261 at RNASEL, hazard ratio (HR), 0.35, 95% CI, 0.18-0.66; p=0.002; rs915927 in XRCC1, HR, 1.91, 95% CI, 1.21-3.02; p=0.009; and rs2494750 at AKT1, HR, 0.45, 95% CI, 0.23-0.90; p=0.016). These results confirm the association of genetic variation in three genes with PCa lethality in a cohort of men with an inherited susceptibility to the disease and provide validation evidence that germline SNPs provide prognostic information for PCa patients. Development of a panel of germline biomarkers with clinical utility for distinguishing patients at detection who have an increased risk for fatal PCa is warranted. What's new? Genetic variants involved in prostate cancer are promising candidate biomarkers of clinical outcome, particularly mortality. Previous investigation identified 22 germline variants associated with lethal prostate cancer. Here, analysis of those variants in high-risk patients from families with hereditary prostate cancer validates the association of three single nucleotide polymorphisms (SNPs) with lethal disease. The validated SNPs were located in the genes RNASEL, XRCC1, and AKT1. The findings indicate that germline SNPs may provide prognostic information for distinguishing patients who are at increased risk for progression to fatal prostate cancer. C1 [Karyadi, Danielle M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Zhao, Shanshan; He, Qianchuan; McIntosh, Laura; Wright, Jonathan L.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Wright, Jonathan L.] Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. [Feng, Ziding] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. RP Stanford, JL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B874, Seattle, WA 98109 USA. EM jstanfor@fhcrc.org OI Ostrander, Elaine/0000-0001-6075-9738 FU National Cancer Institute [R01 CA080122]; Fred Hutchinson Cancer Research Center; Intramural Program of the National Human Genome Research Institute; Prostate Cancer Foundation FX Grant sponsor: National Cancer Institute; Grant number: R01 CA080122; Grant sponsor: Fred Hutchinson Cancer Research Center; Grant sponsor: Intramural Program of the National Human Genome Research Institute; Grant sponsor: Prostate Cancer Foundation NR 28 TC 3 Z9 3 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2015 VL 136 IS 9 BP 2166 EP 2171 DI 10.1002/ijc.29241 PG 6 WC Oncology SC Oncology GA CB9SI UT WOS:000349972300017 PM 25273821 ER PT J AU Lee, MS Lee, B Park, KE Utsuki, T Shin, T Oh, CW Kim, HR AF Lee, Min-Sup Lee, Bonggi Park, Kyoung-Eun Utsuki, Tadanobu Shin, Taisun Oh, Chul Woong Kim, Hyeung-Rak TI Dieckol enhances the expression of antioxidant and detoxifying enzymes by the activation of Nrf2-MAPK signalling pathway in HepG2 cells SO FOOD CHEMISTRY LA English DT Article DE Dieckol; Hemeoxygenase-1; NAD(P)H:quinine oxidoreductase 1; Glutathione S-transferase; Nrf2; MAPK ID MEDIATED GENE-EXPRESSION; RESPONSE ELEMENT; ECKLONIA-STOLONIFERA; CYTOPROTECTIVE GENES; NRF2; INDUCTION; MECHANISM; PROTEIN; STRESS; MICE AB Dieckol was previously reported to exhibit antioxidant and anticancer activities in vitro studies. In this study, we characterised the mechanism underlying the dieckol-mediated expression of antioxidant and detoxifying enzymes. Dieckol suppressed the production of intracellular reactive oxygen species in the presence or absence of H2O2 and increased glutathione level in HepG2 cells. Dieckol enhanced the activities of antioxidant enzymes, and the expression of detoxifying enzymes including heme oxygenase-1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO1), and glutathione S-transferase (GST) in HepG2 cells. Enhanced expression of antioxidant and detoxifying enzymes by dieckol was presumed to be the activation of the nuclear factor erythroid-derived 2-like 2 (Nrf2) demonstrated by its nuclear translocation and transcriptional activity via activation of mitogen-activated protein kinases in HepG2 cells. Furthermore, we demonstrated dieckol induced the expression of HO-1 in mouse liver. These results demonstrate that the dieckol-mediated cytoprotection in HepG2 cells is mediated through a ROS-independent up-regulation of antioxidant and detoxifying enzymes via Nrf2 activation as well as its intrinsic antioxidant activity, suggesting that dieckol may be used as a natural cytoprotective agent. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Lee, Min-Sup; Park, Kyoung-Eun; Kim, Hyeung-Rak] Pukyong Natl Univ, Dept Food Sci & Nutr, Pusan 608737, South Korea. [Lee, Bonggi] NICHHD, NIH, Bethesda, MD 20892 USA. [Utsuki, Tadanobu] Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA. [Shin, Taisun] Chonnam Natl Univ, Dept Food Sci & Nutr, Yeosu 550749, South Korea. [Oh, Chul Woong] Pukyong Natl Univ, Dept Marine Biol, Pusan 608737, South Korea. RP Kim, HR (reprint author), Pukyong Natl Univ, Dept Food Sci & Nutr, Pusan 608737, South Korea. EM hrkim@pknu.ac.kr FU Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2013R1A1A2009588] FX This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013R1A1A2009588). NR 32 TC 14 Z9 15 U1 0 U2 31 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 EI 1873-7072 J9 FOOD CHEM JI Food Chem. PD MAY 1 PY 2015 VL 174 BP 538 EP 546 DI 10.1016/j.foodchem.2014.11.090 PG 9 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA AZ2UP UT WOS:000348088000073 PM 25529716 ER PT J AU Livingston, WS Rusch, HL Nersesian, PV Baxter, T Mysliwiec, V Gill, JM AF Livingston, Whitney S. Rusch, Heather L. Nersesian, Paula V. Baxter, Tristin Mysliwiec, Vincent Gill, Jessica M. TI Improved sleep in military personnel is associated with changes in the expression of inflammatory genes and improvement in depression symptoms SO FRONTIERS IN PSYCHIATRY LA English DT Article DE gene expression; insomnia; inflammation; depression; military personnel ID POSTTRAUMATIC-STRESS-DISORDER; C-REACTIVE PROTEIN; SERVICE MEMBERS; COMBAT VETERANS; MOOD DISORDERS; MENTAL-HEALTH; CANCER CELLS; PTSD; INSOMNIA; DISTURBANCE AB Study objectives: Sleep disturbances are common in military personnel and are associated with increased risk for psychiatric morbidity, including posttraumatic stress disorder (PTSD) and depression, as well as inflammation. Improved sleep quality is linked to reductions in inflammatory bio-markers; however, the underlying mechanisms remain elusive. Methods: In this study, we examine whole genome expression changes related to improved sleep in 68 military personnel diagnosed with insomnia. Subjects were classified into the following groups and then compared: improved sleep (n = 46), or non-improved sleep (n = 22) following three months of standard of care treatment for insomnia. Within subject differential expression was determined from microarray data using the Partek Genomics Suite analysis program and the ingenuity pathway analysis (IPA) was used to determine key regulators of observed expression changes. Changes in symptoms of depression and PTSD were also compared. Results: At baseline, both groups were similar in demographics, clinical characteristics, and gene-expression profiles. The microarray data revealed that 217 coding genes were differentially expressed at the follow-up-period compared to baseline in the participants with improved sleep. Expression of inflammatory cytokines were reduced including IL1f3, IL-6, IL-8, and IL-13, with fold changes ranging from 3.19 to 2.1, and there were increases in the expression of inflammatory regulatory genes including toll-like receptors 1, 4, 7, and 8 in the improved sleep group. IPA revealed six gene networks, including ubiquitin, which was a major regulator in these gene-expression changes. The improved sleep group also had a significant reduction in the severity of depressive symptoms. Conclusion: Interventions that restore sleep likely reduce the expression of inflammatory genes, which relate to ubiquitin genes and relate to reductions in depressive symptoms. C1 [Livingston, Whitney S.; Rusch, Heather L.; Nersesian, Paula V.; Gill, Jessica M.] NINR, NIH, Bethesda, MD 20892 USA. [Nersesian, Paula V.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. [Baxter, Tristin; Mysliwiec, Vincent] Madigan Army Med Ctr, Tacoma, WA 98431 USA. RP Livingston, WS (reprint author), NINR, 1 Cloister Court,Room 259, Bethesda, MD 20892 USA. EM whitney.livingston@nih.gov NR 60 TC 5 Z9 5 U1 3 U2 4 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-0640 J9 FRONT PSYCHIATRY JI Front. Psychiatry PD APR 30 PY 2015 VL 6 AR 59 DI 10.3389/fpsyt.2015.00059 PG 15 WC Psychiatry SC Psychiatry GA CV5YN UT WOS:000364347500001 PM 25983695 ER PT J AU Liu, HX Hu, Y French, SW Gonzalez, FJ Wan, YJY AF Liu, Hui-Xin Hu, Ying French, Samuel W. Gonzalez, Frank J. Wan, Yu-Jui Yvonne TI Forced expression of fibroblast growth factor 21 reverses the sustained impairment of liver regeneration in hPPAR alpha(PAC) mice due to dysregulated bile acid synthesis SO ONCOTARGET LA English DT Article DE nuclear receptor; metabolism; proliferation; bile acid; species differences ID FARNESOID X RECEPTOR; PPAR-ALPHA; PARTIAL-HEPATECTOMY; NUCLEAR RECEPTOR; OB/OB MICE; MOUSE; METABOLISM; PROTECTS; INJURY; FGF21 AB Peroxisome proliferator activated receptor alpha (PPAR alpha) stimulates hepatocellular proliferation is species-specific. Activation of mouse, but not human, PPAR alpha induces hepatocellular proliferation, hepatomegaly, and liver cancer. Here we tested the hypothesis that human and mouse PPAR alpha affects liver regeneration differentially. PPAR alpha-humanized mice (hPPAR alpha(PAC)) were similar to wild type mice in responding to fasting-induced PPAR alpha signaling. However, these mouse livers failed to regenerate in response to partial hepatectomy (PH). The liver-to-body weight ratios did not recover even 3 months after PH in hPPAR alpha(PAC). The mouse PPAR alpha-mediated down-regulation of let-7c was absent in hPPAR alpha(PAC), which might partially be responsible for impaired proliferation. After PH, hPPAR alpha(PAC) displayed steatosis, necrosis, and inflammation mainly in periportal zone 1, which suggested bile-induced toxicity. Quantification of hepatic bile acids (BA) revealed BA overload with increased hydrophobic BA in hPPAR alpha(PAC). Forced FGF21 expression in partial hepatectomized hPPAR alpha(PAC) reduced hepatic steatosis, prevented focal necrosis, and restored liver mass. Compared to mouse PPAR alpha, human PPAR alpha has a reduced capacity to regulate metabolic pathways required for liver regeneration. In addition, FGF21 can compensate for the reduced ability of human PPAR alpha in stimulating liver regeneration, which suggests the potential application of FGF21 in promoting hepatic growth in injured and steatotic livers in humans. C1 [Liu, Hui-Xin; Hu, Ying; Wan, Yu-Jui Yvonne] Univ Calif Davis, Dept Med Pathol & Lab Med, Sacramento, CA 95817 USA. [French, Samuel W.] Harbor UCLA Med Ctr, Dept Pathol & Lab Med, Torrance, CA 90509 USA. [Gonzalez, Frank J.] NCI, NIH, Lab Metab, Bethesda, MD 20892 USA. RP Wan, YJY (reprint author), Univ Calif Davis, Dept Med Pathol & Lab Med, Sacramento, CA 95817 USA. EM yjywan@ucdavis.edu FU National Institutes of Health [CA53596, DK092100] FX The authors thank Ms. Irene Ly for technical assistance and Ms. Lisa Teixeira for editing the manuscript. This study is supported by grants funded by National Institutes of Health CA53596 and DK092100. NR 48 TC 2 Z9 2 U1 1 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD APR 30 PY 2015 VL 6 IS 12 BP 9686 EP 9700 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CO0WO UT WOS:000358874600007 PM 25991671 ER PT J AU Hoots, WK Abkowitz, JL Coller, BS DiMichele, DM AF Hoots, W. Keith Abkowitz, Janis L. Coller, Barry S. DiMichele, Donna M. TI Planning for the future workforce in hematology research SO BLOOD LA English DT Article AB The medical research and training enterprise in the United States is complex in both its scope and implementation. Accordingly, adaptations to the associated workforce needs present particular challenges. This is particularly true for maintaining or expanding national needs for physician-scientists where training resource requirements and competitive transitional milestones are substantial. For the individual, these phenomena can produce financial burden, prolong the career trajectory, and significantly influence career pathways. Hence, when national data suggest that future medical research needs in a scientific area may be met in a less than optimal manner, strategies to expand research and training capacity must follow. This article defines such an exigency for research and training in nonneoplastic hematology and presents potential strategies for addressing these critical workforce needs. The considerations presented herein reflect a summary of the discussions presented at 2 workshops cosponsored by the National Heart, Lung, and Blood Institute and the American Society of Hematology. C1 [Hoots, W. Keith; DiMichele, Donna M.] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. [Abkowitz, Janis L.] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. [Coller, Barry S.] Rockefeller Univ Hosp, Allen & Francis Adler Lab Blood & Vasc Biol, New York, NY 10021 USA. RP Hoots, WK (reprint author), NHLBI, Div Blood Dis & Resources, NIH, 6701 Rockledge Dr,Room 9136, Bethesda, MD 20892 USA. EM hootswk@nhlbi.nih.gov FU NHLBI NIH HHS [K12 HL087165] NR 9 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD APR 30 PY 2015 VL 125 IS 18 BP 2745 EP 2752 DI 10.1182/blood-201501-617811 PG 8 WC Hematology SC Hematology GA CJ7OR UT WOS:000355686600006 PM 25758827 ER PT J AU Calvo, KR Price, S Braylan, RC Oliveira, JB Lenardo, M Fleisher, TA Rao, VK AF Calvo, Katherine R. Price, Susan Braylan, Raul C. Oliveira, Joao Bosco Lenardo, Michael Fleisher, Thomas A. Rao, V. Koneti TI JMML and RALD (Ras-associated autoimmune leukoproliferative disorder): common genetic etiology yet clinically distinct entities SO BLOOD LA English DT Article ID JUVENILE MYELOMONOCYTIC LEUKEMIA; MYELODYSPLASTIC SYNDROMES; LYMPHOPROLIFERATIVE SYNDROME; BLOOD MONOCYTES; FLOW-CYTOMETRY; MUTATIONS; CLASSIFICATION; LEUKEMOGENESIS; IMPROVEMENT; CHILDHOOD AB Ras-associated autoimmune leukoproliferative disorder (RALD) is a chronic, nonmalignant condition that presents with persistent monocytosis and is often associated with leukocytosis, lymphoproliferation, and autoimmune phenomena. RALD has clinical and laboratory features that overlap with those of juvenile myelomonocytic leukemia (JMML) and chronicmyelomonocytic leukemia (CMML), including identical somatic mutations in KRAS or NRAS genes noted in peripheral blood mononuclear cells. Long-term follow-up of these patients suggests that RALD has an indolent clinical course whereas JMML is fatal if left untreated. Immunophenotyping peripheral blood from RALD patients shows characteristic circulating activated monocytes and polyclonal CD10(+) B cells. Distinguishing RALD from JMML and CMML has implications for clinical care and prognosis. C1 [Calvo, Katherine R.; Braylan, Raul C.; Fleisher, Thomas A.] Ctr Clin, Dept Lab Med, Bethesda, MD USA. [Price, Susan; Lenardo, Michael; Rao, V. Koneti] NIAID, Immunol Lab, Bethesda, MD 20892 USA. [Price, Susan; Lenardo, Michael; Rao, V. Koneti] NIAID, Clin Genom Program, NIH, Bethesda, MD 20892 USA. [Oliveira, Joao Bosco] Inst Med Integral Prof Fernando Figueira, Recife, PE, Brazil. RP Rao, VK (reprint author), NIAID, NIH, 10 Ctr Dr,Bldg 10,Room 12C106,MSC 1899, Bethesda, MD 20892 USA. EM koneti@nih.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health Clinical Center FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and the National Institutes of Health Clinical Center. NR 39 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD APR 30 PY 2015 VL 125 IS 18 BP 2753 EP 2758 DI 10.1182/blood2014-11-567917 PG 6 WC Hematology SC Hematology GA CJ7OR UT WOS:000355686600007 PM 25691160 ER PT J AU Roberto, A Castagna, L Zanon, V Bramanti, S Crocchiolo, R McLaren, JE Gandolfi, S Tentorio, P Sarina, B Timofeeva, I Santoro, A Carlo-Stella, C Bruno, B Carniti, C Corradini, P Gostick, E Ladell, K Price, DA Roederer, M Mavilio, D Lugli, E AF Roberto, Alessandra Castagna, Luca Zanon, Veronica Bramanti, Stefania Crocchiolo, Roberto McLaren, James E. Gandolfi, Sara Tentorio, Paolo Sarina, Barbara Timofeeva, Inna Santoro, Armando Carlo-Stella, Carmelo Bruno, Benedetto Carniti, Cristiana Corradini, Paolo Gostick, Emma Ladell, Kristin Price, David A. Roederer, Mario Mavilio, Domenico Lugli, Enrico TI Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; RECEPTOR EXCISION CIRCLE; POSTTRANSPLANTATION CYCLOPHOSPHAMIDE; IMMUNE RECONSTITUTION; ADOPTIVE IMMUNOTHERAPY; CLONAL COMPOSITION; PERIPHERAL-BLOOD; ANTIGEN; PHENOTYPE; PROLIFERATION AB Early T-cell reconstitution following allogeneic transplantation depends on the persistence and function of T cells that are adoptively transferred with the graft. Posttransplant cyclophosphamide (pt-Cy) effectively prevents alloreactive responses from unmanipulated grafts, but its effect on subsequent immune reconstitution remains undetermined. Here, we show that T memory stem cells (TSCM), which demonstrated superior reconstitution capacity in preclinical models, are the most abundant circulating T-cell population in the early days following haploidentical transplantation combined with pt-Cy and precede the expansion of effector cells. Transferred naive, but not TSCM or conventional memory cells preferentially survive cyclophosphamide, thus suggesting that posttransplant TSCM originate from naive precursors. Moreover, donor naive T cells specific for exogenous and self/tumor antigens persist in the host and contribute to peripheral reconstitution by differentiating into effectors. Similarly, pathogen-specific memory T cells generate detectable recall responses, but only in the presence of the cognate antigen. We thus define the cellular basis of T-cell reconstitution following pt-Cy at the antigen-specific level and propose to explore naive-derived TSCM in the clinical setting to overcome immunodeficiency. C1 [Roberto, Alessandra; Zanon, Veronica; Tentorio, Paolo; Mavilio, Domenico; Lugli, Enrico] Humanitas Clin & Res Ctr, Unit Clin & Expt Immunol, I-20089 Milan, Italy. [Castagna, Luca; Bramanti, Stefania; Crocchiolo, Roberto; Gandolfi, Sara; Sarina, Barbara; Timofeeva, Inna; Santoro, Armando; Carlo-Stella, Carmelo] Humanitas Canc Ctr, Hematol & Bone Marrow Transplant Unit, Milan, Italy. [McLaren, James E.; Gostick, Emma; Ladell, Kristin; Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales. [Carlo-Stella, Carmelo; Mavilio, Domenico] Univ Milan, Dept Med Biotechnol & Translat Med BioMeTra, Milan, Italy. [Bruno, Benedetto] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Turin, Italy. [Carniti, Cristiana; Corradini, Paolo] Ist Nazl Tumori, Dept Haematol & Pediat Oncohaematol, I-20133 Milan, Italy. [Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mavilio, D (reprint author), Humanitas Clin & Res Ctr, Unit Clin & Expt Immunol, Via Alessandro Manzoni 113, I-20089 Milan, Italy. EM domenico.mavilio@humanitas.it; enrico.lugli@humanitasresearch.it RI Price, David/C-7876-2013; Ladell, Kristin/C-8301-2013; Carniti, Cristiana/B-8665-2017; OI Price, David/0000-0001-9416-2737; Ladell, Kristin/0000-0002-9856-2938; Carniti, Cristiana/0000-0003-1039-1757; Carlo-Stella, Carmelo/0000-0003-3144-0124; Mavilio, Domenico/0000-0001-6147-0952; Corradini, Paolo/0000-0002-9186-1353; Castagna, Luca/0000-0002-6239-7387 FU Fondazione Cariplo [Ricerca Biomedica 2012/0683]; European Union [322093]; Associazione Italiana per la Ricerca sul Cancro [MFAG 10607, IG 14687]; Italian Ministry of Health [GR-2008-1135082, GR-2011-02347324]; National Institutes of Allergy and Infectious Diseases; Humanitas Intramural Research and Clinical Funding Programs; Fondazione Italiana per la Ricerca sul Cancro FX This work was supported by grants from the Fondazione Cariplo (Grant Ricerca Biomedica 2012/0683 to E.L.), the European Union (Marie Curie Career Integration Grant 322093 to E.L.), and the Associazione Italiana per la Ricerca sul Cancro (MFAG 10607 to E.L. and IG 14687 to D.M), by the Italian Ministry of Health (Bando Giovani Ricercatori GR-2008-1135082 to D.M. and GR-2011-02347324 to E.L.), as well as funds provided by the Intramural Program of the National Institutes of Allergy and Infectious Diseases (to M.R.) and Humanitas Intramural Research and Clinical Funding Programs (to D.M. and L.C.). A.R. is a recipient of the Guglielmina Lucatello e Gino Mazzega Fellowship from the Fondazione Italiana per la Ricerca sul Cancro. D.A.P. is a Wellcome Trust Senior Investigator. NR 46 TC 20 Z9 20 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD APR 30 PY 2015 VL 125 IS 18 BP 2855 EP 2864 DI 10.1182/blood-2014-11-608406 PG 10 WC Hematology SC Hematology GA CJ7OR UT WOS:000355686600018 PM 25742699 ER PT J AU Maxwell, EK Campbell, JD Spira, A Baxevanis, AD AF Maxwell, Evan K. Campbell, Joshua D. Spira, Avrum Baxevanis, Andreas D. TI SubmiRine: assessing variants in microRNA targets using clinical genomic data sets SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENETIC-VARIATION; COMPLEX TRAITS; SITES; EXPRESSION; DISEASE; BINDING; SNP; ASSOCIATION; POLYMORPHISMS; RECOGNITION AB MicroRNAs (miRNAs) regulate gene expression by binding to partially complementary sequences on target mRNA transcripts, thereby causing their degradation, deadenylation, or inhibiting their translation. Genomic variants can alter miRNA regulation by modifying miRNA target sites, and multiple human disease phenotypes have been linked to such miRNA target site variants (miR-TSVs). However, systematic genome-wide identification of functional miR-TSVs is difficult due to high false positive rates; functional miRNA recognition sequences can be as short as six nucleotides, with the human genome encoding thousands of miRNAs. Furthermore, while large-scale clinical genomic data sets are becoming increasingly commonplace, existing miR-TSV prediction methods are not designed to analyze these data. Here, we present an open-source tool called SubmiRine that is designed to perform efficient miR-TSV prediction systematically on variants identified in novel clinical genomic data sets. Most importantly, SubmiRine allows for the prioritization of predicted miR-TSVs according to their relative probability of being functional. We present the results of SubmiRine using integrated clinical genomic data from a large-scale cohort study on chronic obstructive pulmonary disease (COPD), making a number of high-scoring, novel miR-TSV predictions. We also demonstrate SubmiRine's ability to predict and prioritize known miR-TSVs that have undergone experimental validation in previous studies. C1 [Maxwell, Evan K.; Campbell, Joshua D.; Spira, Avrum; Baxevanis, Andreas D.] NHGRI, Computat & Stat Genom Branch, NIH, Bethesda, MD 20892 USA. [Maxwell, Evan K.; Campbell, Joshua D.; Spira, Avrum] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. [Campbell, Joshua D.; Spira, Avrum] Boston Univ, Div Computat Biomed, Dept Med, Sch Med, Boston, MA 02215 USA. RP Baxevanis, AD (reprint author), NHGRI, Computat & Stat Genom Branch, NIH, Bethesda, MD 20892 USA. EM andy@mail.nih.gov FU Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health FX Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. Funding for open access charge: Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 44 TC 3 Z9 3 U1 0 U2 2 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 APR 30 PY 2015 VL 43 IS 8 BP 3886 EP 3898 DI 10.1093/nar/gkv256 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CJ2LV UT WOS:000355317200009 PM 25813044 ER PT J AU Blatti, C Kazemian, M Wolfe, S Brodsky, M Sinha, S AF Blatti, Charles Kazemian, Majid Wolfe, Scot Brodsky, Michael Sinha, Saurabh TI Integrating motif, DNA accessibility and gene expression data to build regulatory maps in an organism SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR-BINDING; OPEN CHROMATIN; DROSOPHILA; GENOME; ELEMENTS; PREDICTION; ENHANCERS; REGIONS; SITES; POLYCOMB AB Characterization of cell type specific regulatory networks and elements is a major challenge in genomics, and emerging strategies frequently employ high-throughput genome-wide assays of transcription factor (TF) to DNA binding, histone modifications or chromatin state. However, these experiments remain too difficult/expensive for many laboratories to apply comprehensively to their system of interest. Here, we explore the potential of elucidating regulatory systems in varied cell types using computational techniques that rely on only data of gene expression, low-resolution chromatin accessibility, and TF-DNA binding specificities ('motifs'). We show that static computational motif scans overlaid with chromatin accessibility data reasonably approximate experimentally measured TF-DNA binding. We demonstrate that predicted binding profiles and expression patterns of hundreds of TFs are sufficient to identify major regulators of similar to 200 spatiotemporal expression domains in the Drosophila embryo. We are then able to learn reliable statistical models of enhancer activity for over 70 expression domains and apply those models to annotate domain specific enhancers genome-wide. Throughout this work, we apply our motif and accessibility based approach to comprehensively characterize the regulatory network of fruitfly embryonic development and show that the accuracy of our computational method compares favorably to approaches that rely on data from many experimental assays. C1 [Blatti, Charles; Sinha, Saurabh] Univ Illinois, Dept Comp Sci, Urbana, IL 61801 USA. [Kazemian, Majid] NHLBI, NIH, Bethesda, MD 20892 USA. [Wolfe, Scot; Brodsky, Michael] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01655 USA. [Wolfe, Scot] Univ Massachusetts, Sch Med, Dept Mol Med, Worcester, MA 01655 USA. [Brodsky, Michael] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01655 USA. [Sinha, Saurabh] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA. RP Sinha, S (reprint author), Univ Illinois, Dept Comp Sci, 1304 W Springfield Ave, Urbana, IL 61801 USA. EM sinhas@illinois.edu OI Kazemian, Majid/0000-0001-7080-8820 FU National Institutes of Health [1R01GM085233-01]; National Science Foundation [EFRI-1136913]; Cohen Graduate Fellowship FX This work was supported by the National Institutes of Health [1R01GM085233-01 to S.S.]; National Science Foundation [EFRI-1136913 to S.S.]; and Cohen Graduate Fellowship (awarded to C.B.). NR 66 TC 6 Z9 6 U1 3 U2 13 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 APR 30 PY 2015 VL 43 IS 8 BP 3998 EP 4012 DI 10.1093/nar/gkv195 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CJ2LV UT WOS:000355317200018 PM 25791631 ER PT J AU Lujan, SA Clark, AB Kunkel, TA AF Lujan, Scott A. Clark, Alan B. Kunkel, Thomas A. TI Differences in genome-wide repeat sequence instability conferred by proofreading and mismatch repair defects SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-POLYMERASE-EPSILON; REPLICATION FORK; SYNTHESIS ERRORS; STRUCTURAL BASIS; YEAST; MUTATIONS; CANCER; DELTA; FIDELITY; ROLES AB Mutation rates are used to calibrate molecular clocks and to link genetic variants with human disease. However, mutation rates are not uniform across each eukaryotic genome. Rates for insertion/deletion (indel) mutations have been found to vary widely when examined in vitro and at specific loci in vivo. Here, we report the genome-wide rates of formation and repair of indels made during replication of yeast nuclear DNA. Using over 6000 indels accumulated in four mismatch repair (MMR) defective strains, and statistical corrections for false negatives, we find that indel rates increase by 100 000-fold with increasing homonucleotide run length, representing the greatest effect on replication fidelity of any known genomic parameter. Nonetheless, long genomic homopolymer runs are overrepresented relative to random chance, implying positive selection. Proofreading defects in the replicative polymerases selectively increase indel rates in short repetitive tracts, likely reflecting the distance over which Pols delta and I mu interact with duplex DNA upstream of the polymerase active site. In contrast, MMR defects hugely increase indel mutagenesis in long repetitive sequences. Because repetitive sequences are not uniformly distributed among genomic functional elements, the quantitatively different consequences on genome-wide repeat sequence instability conferred by defects in proofreading and MMR have important biological implications. C1 [Lujan, Scott A.; Clark, Alan B.; Kunkel, Thomas A.] NIEHS, Genome Instabil & Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Genome Instabil & Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov FU Division of Intramural Research of the National Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES065070]; National Institutes of Health FX Division of Intramural Research of the National Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES065070 to T.K.]. Funding for open access charge: National Institutes of Health. NR 41 TC 4 Z9 4 U1 2 U2 6 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 APR 30 PY 2015 VL 43 IS 8 BP 4067 EP 4074 DI 10.1093/nar/gkv271 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CJ2LV UT WOS:000355317200023 PM 25824945 ER PT J AU Maslowska, KH Makiela-Dzbenska, K Fijalkowska, IJ Schaaper, RM AF Maslowska, Katarzyna H. Makiela-Dzbenska, Karolina Fijalkowska, Iwona J. Schaaper, Roel M. TI Suppression of the E-coli SOS response by dNTP pool changes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-POLYMERASE-V; RECA PROTEIN; CONSTITUTIVE EXPRESSION; INDUCED-MUTAGENESIS; MUTATOR ACTIVITY; RIBONUCLEOTIDE REDUCTASE; NUCLEOSIDE TRIPHOSPHATES; PROPHAGE INDUCTION; REPLICATION FORKS; LAMBDA REPRESSOR AB The Escherichia coli SOS system is a well-established model for the cellular response to DNA damage. Control of SOS depends largely on the RecA protein. When RecA is activated by single-stranded DNA in the presence of a nucleotide triphosphate cofactor, it mediates cleavage of the LexA repressor, leading to expression of the 30(+)-member SOS regulon. RecA activation generally requires the introduction of DNA damage. However, certain recA mutants, like recA730, bypass this requirement and display constitutive SOS expression as well as a spontaneous (SOS) mutator effect. Presently, we investigated the possible interaction between SOS and the cellular deoxynucleoside triphosphate (dNTP) pools. We found that dNTP pool changes caused by deficiencies in the ndk or dcd genes, encoding nucleoside diphosphate kinase and dCTP deaminase, respectively, had a strongly suppressive effect on constitutive SOS expression in recA730 strains. The suppression of the recA730 mutator effect was alleviated in a lexA-deficient background. Overall, the findings suggest a model in which the dNTP alterations in the ndk and dcd strains interfere with the activation of RecA, thereby preventing LexA cleavage and SOS induction. C1 [Maslowska, Katarzyna H.; Schaaper, Roel M.] NIEHS, Genome Integr & Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Maslowska, Katarzyna H.; Makiela-Dzbenska, Karolina; Fijalkowska, Iwona J.] Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland. RP Schaaper, RM (reprint author), NIEHS, Genome Integr & Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM iwonaf@ibb.waw.pl; schaaper@niehs.nih.gov RI Makiela-Dzbenska, Karolina/E-6751-2016; Fijalkowska, Iwona/I-7796-2016; OI Maslowska, Katarzyna/0000-0003-3393-8225 FU Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES065086]; International PhD Projects Program of the Foundation for Polish Science [MPD/2009-3/2]; European Union Regional Development Fund; National Institute of Environmental Health Sciences FX The Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences [project number Z01 ES065086]; International PhD Projects Program of the Foundation for Polish Science [project number MPD/2009-3/2] "Studies of Nucleic Acids and Proteins - from Basic to Applied Research" and European Union Regional Development Fund. Funding for the open access charge: the National Institute of Environmental Health Sciences. NR 75 TC 3 Z9 3 U1 2 U2 9 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 APR 30 PY 2015 VL 43 IS 8 BP 4109 EP 4120 DI 10.1093/nar/gkv217 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CJ2LV UT WOS:000355317200027 PM 25824947 ER PT J AU Perez-Berna, AJ Marion, S Chichon, FJ Fernandez, JJ Winkler, DC Carrascosa, JL Steven, AC Siber, A San Martin, C AF Perez-Berna, Ana J. Marion, Sanjin Javier Chichon, F. Fernandez, Jose J. Winkler, Dennis C. Carrascosa, Jose L. Steven, Alasdair C. Siber, Antonio San Martin, Carmen TI Distribution of DNA-condensing protein complexes in the adenovirus core SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CRYOELECTRON TOMOGRAPHY; NUCLEOPROTEIN CORES; CHROMATIN-STRUCTURE; MOLECULAR-DYNAMICS; GENOME PACKING; CROSS-LINKING; VIRUS; TYPE-2; ORGANIZATION; VIRION AB Genome packing in adenovirus has long evaded precise description, since the viral dsDNA molecule condensed by proteins (core) lacks icosahedral order characteristic of the virus protein coating (capsid). We show that useful insights regarding the organization of the core can be inferred from the analysis of spatial distributions of the DNA and condensing protein units (adenosomes). These were obtained from the inspection of cryo-electron tomography reconstructions of individual human adenovirus particles. Our analysis shows that the core lacks symmetry and strict order, yet the adenosome distribution is not entirely random. The features of the distribution can be explained by modeling the condensing proteins and the part of the genome in each adenosome as very soft spheres, interacting repulsively with each other and with the capsid, producing a minimum outward pressure of similar to 0.06 atm. Although the condensing proteins are connected by DNA in disrupted virion cores, in our models a backbone of DNA linking the adenosomes is not required to explain the experimental results in the confined state. In conclusion, the interior of an adenovirus infectious particle is a strongly confined and dense phase of soft particles (adenosomes) without a strictly defined DNA backbone. C1 [Perez-Berna, Ana J.; Javier Chichon, F.; Fernandez, Jose J.; Carrascosa, Jose L.; San Martin, Carmen] CSIC, Ctr Nacl Biotecnol, Dept Macromol Struct, E-28049 Madrid, Spain. [Perez-Berna, Ana J.; Javier Chichon, F.; Carrascosa, Jose L.; San Martin, Carmen] CSIC, Ctr Nacl Biotecnol, NanoBiomed Initiat, E-28049 Madrid, Spain. [Marion, Sanjin; Siber, Antonio] Inst Phys, HR-10000 Zagreb, Croatia. [Winkler, Dennis C.; Steven, Alasdair C.] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. [Siber, Antonio] Jozef Stefan Inst, SI-1000 Ljubljana, Slovenia. RP San Martin, C (reprint author), CSIC, Ctr Nacl Biotecnol, Dept Macromol Struct, Plaza Murillo 2, E-28049 Madrid, Spain. EM asiber@ifs.hr; carmen@cnb.csic.es RI Siber, Antonio/B-8881-2008; Fernandez, Jose-Jesus/A-5084-2008; Chichon Garcia, Francisco Javier/K-5117-2012; San Martin, Carmen/A-4074-2010; Chichon Garcia, Francisco Javier/B-6029-2011; Perez-Berna, Ana/G-2789-2016; OI Siber, Antonio/0000-0003-1665-6541; Fernandez, Jose-Jesus/0000-0003-2222-3355; Chichon Garcia, Francisco Javier/0000-0003-2766-0327; San Martin, Carmen/0000-0001-9799-175X; Chichon Garcia, Francisco Javier/0000-0003-2766-0327; Marion, Sanjin/0000-0002-9892-7378 FU Ministerio de Economia y Competitividad of Spain [BFU2010-16382, BFU2013-41249-P, TIN2012-37483-C03-02, BFU2011-29038]; Spanish Interdisciplinary Network on the Biophysics of Viruses (Biofivinet) [FIS2011-16090-E]; Intramural Research Program of NIAMS; Ministerio de Ciencia e Innovacion of Spain; CSIC Travel Grant [PA1002892] FX Grants from the Ministerio de Economia y Competitividad of Spain [BFU2010-16382, BFU2013-41249-P (to C.S.M.), TIN2012-37483-C03-02 (to J.J.F.), BFU2011-29038 (to J.L.C.), and Spanish Interdisciplinary Network on the Biophysics of Viruses (Biofivinet, FIS2011-16090-E)]; Intramural Research Program of NIAMS (to A.C.S.). A.J.P.-B. was a recipient of a Juan de la Cierva postdoctoral contract from the Ministerio de Ciencia e Innovacion of Spain and was additionally supported by a CSIC Travel Grant PA1002892. Funding for open access charge: BFU2013-41249-P from the Ministerio de Economia y Competitividad of Spain. NR 73 TC 7 Z9 7 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 30 PY 2015 VL 43 IS 8 BP 4274 EP 4283 DI 10.1093/nar/gkv187 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CJ2LV UT WOS:000355317200039 PM 25820430 ER PT J AU Lee, NCO Larionov, V Kouprina, N AF Lee, Nicholas C. O. Larionov, Vladimir Kouprina, Natalay TI Highly efficient CRISPR/Cas9-mediated TAR cloning of genes and chromosomal loci from complex genomes in yeast SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSFORMATION-ASSOCIATED RECOMBINATION; HUMAN ARTIFICIAL CHROMOSOMES; CONDITIONAL CENTROMERE; FUNCTIONAL GENOMICS; SELECTIVE ISOLATION; DELIVERY; CRISPR-CAS9; HAPLOTYPES; REGIONS; BIOLOGY AB Transformation-associated recombination (TAR) protocol allowing the selective isolation of full-length genes complete with their distal enhancer regions and entire genomic loci with sizes up to 250 kb from complex genomes in yeast S. cerevisiae has been developed more than a decade ago. However, its wide spread usage has been impeded by a low efficiency (0.5-2%) of chromosomal region capture during yeast transformants which in turn requires a time-consuming screen of hundreds of colonies. Here, we demonstrate that pre-treatment of genomic DNA with CRISPR-Cas9 nucleases to generate double-strand breaks near the targeted genomic region results in a dramatic increase in the fraction of gene-positive colonies (up to 32%). As only a dozen or less yeast transformants need to be screened to obtain a clone with the desired chromosomal region, extensive experience with yeast is no longer required. A TAR-CRISPR protocol may help to create a bank of human genes, each represented by a genomic copy containing its native regulatory elements, that would lead to a significant advance in functional, structural and comparative genomics, in diagnostics, gene replacement, generation of animal models for human diseases and has a potential for gene therapy. C1 [Lee, Nicholas C. O.; Larionov, Vladimir; Kouprina, Natalay] NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA. RP Kouprina, N (reprint author), NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA. EM kouprinn@mail.nih.gov RI Lee, Nicholas/F-3668-2015; OI lee, nicholas/0000-0003-2628-6599 FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, USA FX Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, USA (V.L. and N.K). Funding for open access charge: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, USA. NR 24 TC 9 Z9 13 U1 4 U2 51 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 APR 30 PY 2015 VL 43 IS 8 AR e55 DI 10.1093/nar/gkv112 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CJ2LV UT WOS:000355317200006 PM 25690893 ER PT J AU Nunes, MRT Faria, NR de Vasconcelos, JM Golding, N Kraemer, MUG de Oliveira, LF Azevedo, RDD da Silva, DEA da Silva, EVP da Silva, SP Carvalho, VL Coelho, GE Cruz, ACR Rodrigues, SG Vianez, JLDG Nunes, BTD Cardoso, JF Tesh, RB Hay, SI Pybus, OG Vasconcelos, PFD AF Teixeira Nunes, Marcio Roberto Faria, Nuno Rodrigues de Vasconcelos, Janaina Mota Golding, Nick Kraemer, Moritz U. G. de Oliveira, Layanna Freitas da Silva Azevedo, Raimunda do Socorro Andrade da Silva, Daisy Elaine Pinto da Silva, Eliana Vieira da Silva, Sandro Patroca Carvalho, Valeria Lima Coelho, Giovanini Evelim Ribeiro Cruz, Ana Cecilia Rodrigues, Sueli Guerreiro da Silva Goncalves Vianez, Joao Lidio, Jr. Diniz Nunes, Bruno Tardelli Cardoso, Jedson Ferreira Tesh, Robert B. Hay, Simon I. Pybus, Oliver G. da Costa Vasconcelos, Pedro Fernando TI Emergence and potential for spread of Chikungunya virus in Brazil SO BMC MEDICINE LA English DT Article DE Chikungunya virus; National surveillance; Public health; Spatial prediction; Statistical methods ID AEDES-ALBOPICTUS; POPULATION-DYNAMICS; AMERICA; INFERENCE; AEGYPTI; IMPACT AB Background: In December 2013, an outbreak of Chikungunya virus (CHIKV) caused by the Asian genotype was notified in the Caribbean. The outbreak has since spread to 38 regions in the Americas. By September 2014, the first autochthonous CHIKV infections were confirmed in Oiapoque, North Brazil, and in Feira de Santana, Northeast Brazil. Methods: We compiled epidemiological and clinical data on suspected CHIKV cases in Brazil and polymerase-chain-reaction-based diagnostic was conducted on 68 serum samples from patients with symptom onset between April and September 2014. Two imported and four autochthonous cases were selected for virus propagation, RNA isolation, full-length genome sequencing, and phylogenetic analysis. We then followed CDC/PAHO guidelines to estimate the risk of establishment of CHIKV in Brazilian municipalities. Results: We detected 41 CHIKV importations and 27 autochthonous cases in Brazil. Epidemiological and phylogenetic analyses indicated local transmission of the Asian CHIKV genotype in Oiapoque. Unexpectedly, we also discovered that the ECSA genotype is circulating in Feira de Santana. The presumed index case of the ECSA genotype was an individual who had recently returned from Angola and developed symptoms in Feira de Santana. We estimate that, if CHIKV becomes established in Brazil, transmission could occur in 94% of municipalities in the country and provide maps of the risk of importation of each strain of CHIKV in Brazil. Conclusions: The etiological strains associated with the early-phase CHIKV outbreaks in Brazil belong to the Asian and ECSA genotypes. Continued surveillance and vector mitigation strategies are needed to reduce the future public health impact of CHIKV in the Americas. C1 [Teixeira Nunes, Marcio Roberto; de Vasconcelos, Janaina Mota; de Oliveira, Layanna Freitas; Andrade da Silva, Daisy Elaine; da Silva, Sandro Patroca; da Silva Goncalves Vianez, Joao Lidio, Jr.; Cardoso, Jedson Ferreira] Minist Hlth, Evandro Chagas Inst, Ctr Technol Innovat, BR-67030000 Ananindeua, PA, Brazil. [Faria, Nuno Rodrigues; Pybus, Oliver G.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England. [Golding, Nick; Kraemer, Moritz U. G.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England. [da Silva Azevedo, Raimunda do Socorro; Pinto da Silva, Eliana Vieira; Carvalho, Valeria Lima; Ribeiro Cruz, Ana Cecilia; Rodrigues, Sueli Guerreiro; Diniz Nunes, Bruno Tardelli; da Costa Vasconcelos, Pedro Fernando] Minist Hlth, Evandro Chagas Inst, Dept Arbovirol & Hemorrhag Fevers, BR-67030000 Ananindeua, PA, Brazil. [Coelho, Giovanini Evelim] Brazilian Minist Hlth, Natl Dengue Control Program, BR-70058900 Brasilia, DF, Brazil. [Tesh, Robert B.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [da Costa Vasconcelos, Pedro Fernando] Para State Univ, Dept Pathol, BR-66087670 Belem, Para, Brazil. RP Nunes, MRT (reprint author), Minist Hlth, Evandro Chagas Inst, Ctr Technol Innovat, BR-67030000 Ananindeua, PA, Brazil. EM marcionunesbrasil@yahoo.com.br RI Hay, Simon/F-8967-2015; Nunes, Marcio Roberto/B-2238-2016; OI Hay, Simon/0000-0002-0611-7272; Pybus, Oliver/0000-0002-8797-2667; Nunes, Marcio Roberto/0000-0001-9739-5499; Faria, Nuno/0000-0001-8839-2798; Golding, Nick/0000-0001-8916-5570 FU Brazilian National Council of Scientific and Technological Development (CNPq) [302032/2011-8]; CNPq [573.739/2008-0, 240/2008/FAPESPA/INCT, 142492/2011-6]; Bill & Melinda Gates Foundation [OPP1053338]; German Academic Exchange Service (DAAD); Wellcome Trust [095066]; Li Ka Shing Foundation; RAPIDD program of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center (FIC), National Institutes of Health (NIH); European Research Council under the European Union [614725] FX We are grateful to the Brazilian Dengue and Chikungunya network composed by 17 national laboratories for their assistance on preliminary screening diagnostics. We thank Oliver Brady for useful discussions and Thessika Hialla Araujo, Luiz Carlos Jr. Alcantara, and Daniele Barbosa Medeiros for providing epidemiological information. MRTN is supported by the Brazilian National Council of Scientific and Technological Development (CNPq) grant no. 302032/2011-8. PFCV is supported by CNPq grant no. 573.739/2008-0 and 240/2008/FAPESPA/INCT. JMV is a PhD student supported by CNPq grant no. 142492/2011-6. NG is funded by a grant from the Bill & Melinda Gates Foundation (#OPP1053338). MUGK is funded by the German Academic Exchange Service (DAAD) graduate scholarship. SIH is funded by a Senior Research Fellowship from the Wellcome Trust (#095066) and receives support from the Li Ka Shing Foundation and also acknowledges funding support from the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center (FIC), National Institutes of Health (NIH). This research has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 614725. NR 42 TC 56 Z9 57 U1 3 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD APR 30 PY 2015 VL 13 AR 102 DI 10.1186/s12916-015-0348-x PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CI0KC UT WOS:000354425000001 ER PT J AU Bullard, KM Ali, MK Imperatore, G Geiss, LS Saydah, SH Albu, JB Cowie, CC Sohler, N Albright, A Gregg, EW AF Bullard, Kai McKeever Ali, Mohammed K. Imperatore, Giuseppina Geiss, Linda S. Saydah, Sharon H. Albu, Jeanine B. Cowie, Catherine C. Sohler, Nancy Albright, Ann Gregg, Edward W. TI Receipt of Glucose Testing and Performance of Two US Diabetes Screening Guidelines, 2007-2012 SO PLOS ONE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; COST-EFFECTIVENESS; PREVENTION PROGRAM; NATIONAL-HEALTH; SECULAR CHANGES; UNITED-STATES; LIFE-STYLE; FOLLOW-UP; PREVALENCE; ADULTS AB Background Screening guidelines are used to help identify prediabetes and diabetes before implementing evidence-based prevention and treatment interventions. We examined screening practices benchmarking against two US guidelines, and the capacity of each guideline to identify dysglycemia. Methods Using 2007-2012 National Health and Nutrition Examination Surveys, we analyzed nationally-representative, cross-sectional data from 5,813 fasting non-pregnant adults aged >= 20 years without self-reported diabetes. We examined proportions of adults eligible for diagnostic glucose testing and those who self-reported receiving testing in the past three years, as recommended by the American Diabetes Association (ADA) and the US Preventive Services Task Force (USPSTF-2008) guidelines. For each screening guideline, we also assessed sensitivity, specificity, and positive (PPV) and negative predictive values in identifying dysglycemia (defined as fasting plasma glucose >= 100 mg/dl or hemoglobin A1c >= 5.7%). Results In 2007-2012, 73.0% and 23.7% of US adults without diagnosed diabetes met ADA and USPSTF-2008 criteria for screening, respectively; and 91.5% had at least one major risk factor for diabetes. Of those ADA- or USPSTF-eligible adults, about 51% reported being tested within the past three years. Eligible individuals not tested were more likely to be lower educated, poorer, uninsured, or have no usual place of care compared to tested eligible adults. Among adults with >= 1 major risk factor, 45.7% reported being tested, and dysglycemia yields (i.e., PPV) ranged from 45.8% (high-risk ethnicity) to 72.6% (self-reported prediabetes). ADA criteria and having any risk factor were more sensitive than the USPSTF-2008 guideline (88.8-97.7% vs. 31.0%) but less specific (13.5-39.7% vs. 82.1%) in recommending glucose testing, resulting in lower PPVs (47.7-54.4% vs. 58.4%). Conclusion Diverging recommendations and variable performance of different guidelines may be impeding national diabetes prevention and treatment efforts. Efforts to align screening recommendations may result in earlier identification of adults at high risk for prediabetes and diabetes. C1 [Bullard, Kai McKeever; Ali, Mohammed K.; Imperatore, Giuseppina; Geiss, Linda S.; Saydah, Sharon H.; Albright, Ann; Gregg, Edward W.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA 30333 USA. [Albu, Jeanine B.] Columbia Univ, St Lukes Roosevelt Hosp Ctr, Dept Med, New York, NY USA. [Cowie, Catherine C.] NIH, NIDDK, Bethesda, MD 20892 USA. [Sohler, Nancy] CUNY City Coll, Sophie Davis Sch Biomed Educ, New York, NY 10031 USA. RP Bullard, KM (reprint author), Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA 30333 USA. EM kbullard@cdc.gov FU NIDDK NIH HHS [P30 DK020541, P60 DK020541] NR 34 TC 4 Z9 4 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 30 PY 2015 VL 10 IS 4 AR e0125249 DI 10.1371/journal.pone.0125249 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0MA UT WOS:000353713100073 PM 25928306 ER PT J AU Subramaniam, KS Skinner, J Ivan, E Mutimura, E Kim, RS Feintuch, CM Portugal, S Anastos, K Crompton, PD Daily, JP AF Subramaniam, Krishanthi S. Skinner, Jeff Ivan, Emil Mutimura, Eugene Kim, Ryung S. Feintuch, Catherine M. Portugal, Silvia Anastos, Kathryn Crompton, Peter D. Daily, Johanna P. TI HIV Malaria Co-Infection Is Associated with Atypical Memory B Cell Expansion and a Reduced Antibody Response to a Broad Array of Plasmodium falciparum Antigens in Rwandan Adults SO PLOS ONE LA English DT Article ID INFECTED INDIVIDUALS; CLINICAL MALARIA; COTRIMOXAZOLE PROPHYLAXIS; ANTIRETROVIRAL THERAPY; IMMUNE-RESPONSES; UNSTABLE MALARIA; PREGNANT-WOMEN; UGANDAN ADULTS; IMMUNOSUPPRESSION; PARASITEMIA AB HIV infected individuals in malaria endemic areas experience more frequent and severe malaria episodes compared to non HIV infected. This clinical observation has been linked to a deficiency in antibody responses to Plasmodium falciparum antigens; however, prior studies have only focused on the antibody response to <0.5% of P. falciparum proteins. To obtain a broader and less-biased view of the effect of HIV on antibody responses to malaria we compared antibody profiles of HIV positive (HIV+) and negative (HIV-) Rwandan adults with symptomatic malaria using a microarray containing 824 P. falciparum proteins. We also investigated the cellular basis of the antibody response in the two groups by analyzing B and T cell subsets by flow cytometry. Although HIV malaria co-infected individuals generated antibodies to a large number of P. falciparum antigens, including potential vaccine candidates, the breadth and magnitude of their response was reduced compared to HIV-individuals. HIV malaria co-infection was also associated with a higher percentage of atypical memory B cells (MBC) (CD19+CD10-CD21-CD27-) compared to malaria infection alone. Among HIV+ individuals the CD4(+) T cell count and HIV viral load only partially explained variability in the breadth of P. falciparum-specific antibody responses. Taken together, these data indicate that HIV malaria co-infection is associated with an expansion of atypical MBCs and a diminished antibody response to a diverse array of P. falciparum antigens, thus offering mechanistic insight into the higher risk of malaria in HIV+ individuals. C1 [Subramaniam, Krishanthi S.] Univ Liverpool, Liverpool Sch Trop Med, Vector Biol Dept, Liverpool L3 5QA, Merseyside, England. [Skinner, Jeff; Portugal, Silvia; Crompton, Peter D.] NIAID, Malaria Infect Biol & Immun Unit, Immunogenet Lab, NIH, Bethesda, MD 20892 USA. [Ivan, Emil] Univ Rwanda, Dept Biomed Lab Sci, Coll Med & Hlth Sci, Kigali, Rwanda. [Mutimura, Eugene] Reg Alliance Sustainable Dev, Kigali, Rwanda. [Kim, Ryung S.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Feintuch, Catherine M.; Daily, Johanna P.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Anastos, Kathryn; Daily, Johanna P.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. RP Daily, JP (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. EM jdaily@einstein.yu.edu RI Crompton, Peter/N-1130-2016; OI Skinner, Jeff/0000-0001-5697-0442 FU Albert Einstein College of Medicine Global Health Pilot Grant; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; [NIAID: 1RC1AI086224] FX This study was supported by A. JPD supported by NIAID: 1RC1AI086224 and an Albert Einstein College of Medicine Global Health Pilot Grant. B. JS, SP and PDC are supported by 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 the manuscript. NR 56 TC 2 Z9 2 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 30 PY 2015 VL 10 IS 4 AR e0124412 DI 10.1371/journal.pone.0124412 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0MA UT WOS:000353713100032 PM 25928218 ER PT J AU Kahn, K Saxena, S Eskandar, E Thakor, N Schieber, M Gale, JT Averbeck, B Eden, U Sarma, SV AF Kahn, Kevin Saxena, Shreya Eskandar, Emad Thakor, Nitish Schieber, Marc Gale, John T. Averbeck, Bruno Eden, Uri Sarma, Sridevi V. TI A systematic approach to selecting task relevant neurons SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Task-related neurons; Neuron selection; Model based; Point processes ID NEURAL SPIKING ACTIVITY; PRIMARY MOTOR CORTEX; FINGER MOVEMENTS; CELLS AB Background: Since task related neurons cannot be specifically targeted during surgery, a critical decision to make is to select which neurons are task-related when performing data analysis. Including neurons unrelated to the task degrade decoding accuracy and confound neurophysiological results. Traditionally, task-related neurons are selected as those with significant changes in firing rate when a stimulus is applied. However, this assumes that neurons' encoding of stimuli are dominated by their firing rate with little regard to temporal dynamics. New method: This paper proposes a systematic approach for neuron selection, which uses a likelihood ratio test to capture the contribution of stimulus to spiking activity while taking into account task-irrelevant intrinsic dynamics that affect firing rates. This approach is denoted as the model deterioration excluding stimulus (MDES) test. Results: MDES is compared to firing rate selection in four case studies: a simulation, a decoding example, and two neurophysiology examples. Comparison with existing methods: The MDES rankings in the simulation match closely with ideal rankings, while firing rate rankings are skewed by task-irrelevant parameters. For decoding, 95% accuracy is achieved using the top 8 MDES-ranked neurons, while the top 12 firing-rate ranked neurons are needed. In the neurophysiological examples, MDES matches published results when firing rates do encode salient stimulus information, and uncovers oscillatory modulations in task-related neurons that are not captured when neurons are selected using firing rates. Conclusions: These case studies illustrate the importance of accounting for intrinsic dynamics when selecting task-related neurons and following the MDES approach accomplishes that. MDES selects neurons that encode task-related information irrespective of these intrinsic dynamics which can bias firing rate based selection. (C) 2015 Elsevier B.V. All rights reserved. C1 [Kahn, Kevin; Thakor, Nitish; Sarma, Sridevi V.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. [Saxena, Shreya] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Schieber, Marc] Univ Rochester, Med Ctr, Sch Med & Dent, Rochester, NY 14642 USA. [Gale, John T.] Cleveland Clin, Dept Neurosci, Cleveland, OH 44195 USA. [Gale, John T.] Cleveland Clin, Ctr Neurol Restorat, Cleveland, OH 44195 USA. [Averbeck, Bruno] NIH, Neuropsychol Lab, Bethesda, MD 20892 USA. [Eden, Uri] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP Kahn, K (reprint author), Johns Hopkins Univ, Inst Computat Med, 3400 N Charles St,Hackerman Hall,Room 318, Baltimore, MD 21218 USA. EM kkahn6@jhmi.edu RI Thakor, Nitish/G-9110-2015 OI Thakor, Nitish/0000-0002-9981-9395 FU Burroughs Wellcome Fund [100727401]; National Science Foundation [1137237] FX K Kahn and SV Sarma were supported by the Burroughs Wellcome Fund (100727401) and the National Science Foundation (1137237). NR 31 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD APR 30 PY 2015 VL 245 BP 156 EP 168 DI 10.1016/j.jneumeth.2015.02.020 PG 13 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CG8XN UT WOS:000353599100015 PM 25746150 ER PT J AU Fukushima, M Saunders, RC Mullarkey, M Doyle, AM Mishkin, M Fujii, N AF Fukushima, Makoto Saunders, Richard C. Mullarkey, Matthew Doyle, Alexandra M. Mishkin, Mortimer Fujii, Naotaka TI An electrocorticographic electrode array for simultaneous recording from medial, lateral, and intrasulcal surface of the cortex in macaque monkeys (vol 233, pg 155, 2014) SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Correction C1 [Fukushima, Makoto; Saunders, Richard C.; Mullarkey, Matthew; Doyle, Alexandra M.; Mishkin, Mortimer] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Fujii, Naotaka] RIKEN, Lab Adapt Intelligence, Brain Sci Inst, Wako, Saitama 3510198, Japan. RP Fukushima, M (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B80,49 Convent Dr, Bethesda, MD 20892 USA. EM makoto_fukushima@me.com OI Fukushima, Makoto/0000-0002-8809-7892 NR 1 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD APR 30 PY 2015 VL 245 BP 205 EP 206 DI 10.1016/j.jneumeth.2015.01.007 PG 2 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CG8XN UT WOS:000353599100019 ER PT J AU Lardinois, O Kirby, PJ Morgan, DL Sills, RC Tomer, KB Deterding, LJ AF Lardinois, O. Kirby, P. J. Morgan, D. L. Sills, R. C. Tomer, K. B. Deterding, L. J. TI Mass spectrometric analysis of rat cerebrospinal fluid proteins following exposure to the neurotoxicant carbonyl sulfide (vol 28, pg 2531, 2014) SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Correction C1 [Lardinois, O.; Tomer, K. B.; Deterding, L. J.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Kirby, P. J.; Morgan, D. L.] NIEHS, Lab Toxicol & Pharmacol, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Sills, R. C.] NIEHS, Cellular & Mol Pathol, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Deterding, LJ (reprint author), NIEHS, Struct Biol Lab, NIH, DHHS, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. NR 1 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-4198 EI 1097-0231 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD APR 30 PY 2015 VL 29 IS 8 BP 782 EP 782 DI 10.1002/rcm.7166 PG 1 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA CF4ZK UT WOS:000352563200010 PM 26406493 ER PT J AU Zhang, ZW Wang, CG Troendle, JF AF Zhang, Zhiwei Wang, Chenguang Troendle, James F. TI Optimizing the order of hypotheses in serial testing of multiple endpoints in clinical trials SO STATISTICS IN MEDICINE LA English DT Article DE chain procedure; fixed sequence; hierarchical testing; multiple comparisons; multiplicity; secondary endpoint ID BONFERRONI PROCEDURE; FIXED-SEQUENCE; GATEKEEPING STRATEGIES; ADJUSTMENT METHODS; SELECTION; EFFICACY; WEIGHTS AB Clinical trials usually collect information on a large number of variables or endpoints, including one or more primary endpoints as well as a number of secondary endpoints representing different aspects of treatment effectiveness and safety. In this article, we focus on serial testing procedures that test multiple endpoints in a pre-specified order, and consider how to optimize the order of endpoints subject to any clinical constraints, with respect to the expected number of successes (i.e., endpoints that reach statistical significance) or the expected gain (if endpoints are associated with numerical utilities). We consider some common approaches to this problem and propose two new approaches: a greedy algorithm based on conditional power and a simulated annealing algorithm that attempts to improve a given sequence in a random and iterative fashion. Simulation results indicate that the proposed algorithms are useful for finding a high-performing sequence, and that optimized fixed sequence procedures can be competitive against traditional multiple testing procedures such as Holm's. The methods and findings are illustrated with two examples concerning migraine and asthma. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Zhang, Zhiwei] US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Wang, Chenguang] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Div Biostat & Bioinformat, Baltimore, MD USA. [Troendle, James F.] NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. RP Zhang, ZW (reprint author), DBS OSB CDRH FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM zhiwei.zhang@fda.hhs.gov NR 33 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD APR 30 PY 2015 VL 34 IS 9 BP 1467 EP 1482 DI 10.1002/sim.6425 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA CF4MV UT WOS:000352524100003 PM 25620627 ER PT J AU Schiffman, M Wentzensen, N AF Schiffman, Mark Wentzensen, Nicolas TI Issues in optimising and standardising the accuracy and utility of the colposcopic examination in the HPV era SO ECANCERMEDICALSCIENCE LA English DT Review DE cervix; screening; colposcopy; HPV ID CERVICAL INTRAEPITHELIAL NEOPLASIA; QUALITY-ASSURANCE PROGRAM; HUMAN-PAPILLOMAVIRUS; POSITIVE WOMEN; CANCER PRECURSORS; DIRECTED BIOPSY; UTERINE CERVIX; SCORING SYSTEM; PERFORMANCE; PREVENTION AB For this tribute to Mario Sideri, we reviewed some of the current issues in colposcopy, many of which we were researching with him. The review concentrates on the impact of HPV testing on cervical screening, specifically on the practice of colposcopy as the major diagnostic procedure in cervical screening programmes. Topics include the changing population of women referred to colposcopy, evolving views of the colposcopic impression, differing approaches to directed and random biopsy, issues in teaching colposcopy using static images, and the development of colposcopy aids, and simplified visual assessment techniques. C1 [Schiffman, Mark; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA. RP Schiffman, M (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, USA 9609 Med Ctr Dr, Rockville, MD 20850 USA. EM schiffmm@mail.nih.gov NR 29 TC 1 Z9 1 U1 0 U2 0 PU CANCER INTELLIGENCE LTD PI BRISTOL PA 11 ALMA VALE RD,, BRISTOL, BS8 2HL, ENGLAND SN 1754-6605 J9 ECANCERMEDICALSCIENC JI eCancerMedicalScience PD APR 29 PY 2015 VL 9 SI SI AR 530 DI 10.3332/ecancer.2015.530 PG 6 WC Oncology SC Oncology GA CQ4YY UT WOS:000360611700005 PM 25987899 ER PT J AU Jankovic, D Feng, CG AF Jankovic, Dragana Feng, Carl G. TI CD4(+) T cell differentiation in infection: amendments to the Th1/Th2 axiom SO FRONTIERS IN IMMUNOLOGY LA English DT Editorial Material DE Thlymphocytes; cytokines; infection; dendriticcells; macrophages; immunoregulation; metabolism; memory; Inc-RNA ID PLASTICITY; POLARIZATION; PROTEINS; SUBSETS C1 [Jankovic, Dragana] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Feng, Carl G.] Univ Sydney, Sydney Med Sch, Dept Infect Dis & Immunol, Sydney, NSW 2006, Australia. RP Jankovic, D (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM djankovic@niaid.nih.gov NR 18 TC 3 Z9 3 U1 2 U2 8 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD APR 29 PY 2015 VL 6 AR 198 DI 10.3389/fimmu.2015.00198 PG 3 WC Immunology SC Immunology GA CI7JK UT WOS:000354939200001 PM 25972870 ER PT J AU Cardoso, FL Herz, J Fernandes, A Rocha, J Sepodes, B Brito, MA McGavern, DB Brites, D AF Cardoso, Filipa L. Herz, Jasmin Fernandes, Adelaide Rocha, Joao Sepodes, Bruno Brito, Maria A. McGavern, Dorian B. Brites, Dora TI Systemic inflammation in early neonatal mice induces transient and lasting neurodegenerative effects SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE Astrocytes; Microglia; Myelination; Neurons; Autotaxin; HMGB1; Neurodevelopment; LPS ID BLOOD-BRAIN-BARRIER; WHITE-MATTER INJURY; LOW-BIRTH-WEIGHT; GROUP BOX 1; PRETERM INFANTS; SEPTIC SHOCK; MATRIX METALLOPROTEINASES; MATERNAL EXPOSURE; SOCIAL-BEHAVIOR; CEREBRAL-CORTEX AB Background: The inflammatory mediator lipopolysaccharide (LPS) has been shown to induce acute gliosis in neonatal mice. However, the progressive effects on the murine neurodevelopmental program over the week that follows systemic inflammation are not known. Thus, we investigated the effects of repeated LPS administration in the first postnatal week in mice, a condition mimicking sepsis in late preterm infants, on the developing central nervous system (CNS). Methods: Systemic inflammation was induced by daily intraperitoneal administration (i.p.) of LPS (6 mg/kg) in newborn mice from postnatal day (PND) 4 to PND6. The effects on neurodevelopment were examined by staining the white matter and neurons with Luxol Fast Blue and Cresyl Violet, respectively. The inflammatory response was assessed by quantifying the expression/activity of matrix metalloproteinases (MMP), toll-like receptor (TLR)-4, high mobility group box (HMGB)-1, and autotaxin (ATX). In addition, B6 CX3CR1(gfp/+) mice combined with cryo-immunofluorescence were used to determine the acute, delayed, and lasting effects on myelination, microglia, and astrocytes. Results: LPS administration led to acute body and brain weight loss as well as overt structural changes in the brain such as cerebellar hypoplasia, neuronal loss/shrinkage, and delayed myelination. The impaired myelination was associated with alterations in the proliferation and differentiation of NG2 progenitor cells early after LPS administration, rather than with excessive phagocytosis by CNS myeloid cells. In addition to disruptions in brain architecture, a robust inflammatory response to LPS was observed. Quantification of inflammatory biomarkers revealed decreased expression of ATX with concurrent increases in HMGB1, TLR-4, and MMP-9 expression levels. Acute astrogliosis (GFAP(+) cells) in the brain parenchyma and at the microvasculature interface together with parenchymal microgliosis (CX3CR1(+) cells) were also observed. These changes preceded the migration/proliferation of CX3CR1(+) cells around the vessels at later time points and the subsequent loss of GFAP(+) astrocytes. Conclusion: Collectively, our study has uncovered a complex innate inflammatory reaction and associated structural changes in the brains of neonatal mice challenged peripherally with LPS. These findings may explain some of the neurobehavioral abnormalities that develop following neonatal sepsis. C1 [Cardoso, Filipa L.; Fernandes, Adelaide; Rocha, Joao; Sepodes, Bruno; Brito, Maria A.; Brites, Dora] Univ Lisbon, Fac Farm, Res Inst Med iMed ULisboa, P-1649003 Lisbon, Portugal. [McGavern, Dorian B.] NINDS, NIH, Bethesda, MD 20892 USA. [Fernandes, Adelaide; Brito, Maria A.; Brites, Dora] Univ Lisbon, Fac Farm, Dept Biochem & Human Biol, P-1649003 Lisbon, Portugal. RP McGavern, DB (reprint author), NINDS, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM mcgavernd@ninds.nih.gov; dbrites@ff.ulisboa.pt RI Fernandes, Adelaide/A-4787-2011; Brites, Dora/M-8293-2013; brito, maria/M-8278-2013; Rocha, Joao/K-1102-2014; Sepodes, Bruno/A-4838-2014; iMed.ULisboa, iMed.ULisboa/C-6292-2014; iMed.ULisboa, NeuronGliaBiol /B-5403-2014; OI Fernandes, Adelaide/0000-0002-2782-9519; Brites, Dora/0000-0002-3024-9777; brito, maria/0000-0002-8493-4649; Rocha, Joao/0000-0002-0303-8085; Sepodes, Bruno/0000-0002-2761-0955; McGavern, Dorian/0000-0001-9568-545X FU National Institutes of Health (NIH) intramural program; FEDER (COMPETE Program); National Portuguese funds (Fundacao para a Ciencia e a Tecnologia - FCT) [PTDC/SAU-FAR/118787/2010, PEst-OE/SAU/UI4013/2011-2013]; FCT [SFRH/BD/62959/2009]; FLAD [2014/CON3/CAN30]; EMBO [ASTF 31-2014] FX This study was supported by the National Institutes of Health (NIH) intramural program (to DBM), by FEDER (COMPETE Program), and by National Portuguese funds (Fundacao para a Ciencia e a Tecnologia - FCT) through the projects PTDC/SAU-FAR/118787/2010 (to DB) and PEst-OE/SAU/UI4013/2011-2013 (to iMed. ULisboa). FLC is a recipient of a PhD fellowship (SFRH/BD/62959/2009) from FCT, a fellowship (2014/CON3/CAN30) from FLAD and a short-term fellowship (ASTF 31-2014) from EMBO. The funding organizations had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 117 TC 10 Z9 11 U1 2 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD APR 29 PY 2015 VL 12 AR UNSP 82 DI 10.1186/s12974-015-0299-3 PG 18 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA CI6CP UT WOS:000354846600001 PM 25924675 ER PT J AU Chan, STS Patel, PR Ransom, TR Henrich, CJ Mckee, TC Goey, AKL Cook, KM Figg, WD McMahon, JB Schnermann, MJ Gustafson, KR AF Chan, Susanna T. S. Patel, Paresma R. Ransom, Tanya R. Henrich, Curtis J. Mckee, Tawnya C. Goey, Andrew K. L. Cook, Kristina M. Figg, William D. McMahon, James B. Schnermann, Martin J. Gustafson, Kirk R. TI Structural Elucidation and Synthesis of Eudistidine A: An Unusual Polycyclic Marine Alkaloid that Blocks Interaction of the Protein Binding Domains of p300 and HIF-1 alpha SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID EUDISTOMA CF RIGIDA; SMALL-MOLECULE; ANTICANCER AGENTS; DRUG DISCOVERY; ARYL KETONES; TUMOR-GROWTH; HYPOXIA; INHIBITORS; TRANSCRIPTION; PATHWAY AB Low oxygen environments are a hallmark of solid tumors, and transcription of many hypoxia-responsive genes needed for survival under these conditions is regulated by the transcription factor HIF-1 (hypoxia-inducible factor 1). Activation of HIF-1 requires binding of its a-subunit (HIF-1 alpha) to the transcriptional coactivator protein p300. Inhibition of the p300/HIF-1 alpha interaction can suppress HIF-I activity. A screen for inhibitors of the protein binding domains of p300 (CHI) and HIF-1 alpha (C-TAD) identified an extract of the marine ascidian Eudistoma sp. as active. Novel heterocyclic alkaloids eudistidines A (1) and B (2) were isolated from the extract, and their structures assigned by spectroscopic analyses. They contain an unprecedented tetracyclic core composed of two pyrimidine rings fused with an imidazole ring. Eudistidine A (I) was synthesized in a concise four-step sequence featuring a condensation/cyclization reaction cascade between 4-(2-aminophenyl)pyrimidin-2-amine (3) and 4-methoxy-phenylglyoxal (4), while eudistidine B (2) was synthesized in a similar fashion with glyoxylic acid (5) in place of 4. Naturally occurring eudistidine A (1) effectively inhibited CH1/C-TAD binding with an IC50 of 75 mu M, and synthetic 1 had similar activity. The eudistidine A (1) scaffold, which can be synthesized in a concise, scalable manner, May provide potential therapeutic lead compounds or molecular probes to study p300/HIP-1 alpha interactions and the role these proteins play in tumor response to low oxygen conditions. The unique structural scaffolds and functional group arrays often found in natural products make these secondary metabolites a rich source of new compounds that can disrupt critical protein protein binding events. C1 [Chan, Susanna T. S.; Ransom, Tanya R.; Henrich, Curtis J.; Mckee, Tawnya C.; McMahon, James B.; Gustafson, Kirk R.] NCI, Mol Targets Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. [Patel, Paresma R.; Schnermann, Martin J.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Patel, Paresma R.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Henrich, Curtis J.] Frederick Natl Lab Canc Res, Basic Sci Program, Leidos Biomed Res Inc, Frederick, MD 21702 USA. [Goey, Andrew K. L.; Cook, Kristina M.; Figg, William D.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Schnermann, MJ (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM martin.schnermann@nih.gov; gustafki@mail.nih.gov RI Figg Sr, William/M-2411-2016 FU NCI-Frederick for extraction; Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research; Federal funds from the National Cancer Institute; National Institutes of Health [HHSN261200800001E] FX We gratefully acknowledge D. Newman (NCI) for organizing and documenting the collection, the Natural Products Support Group at NCI-Frederick for extraction, and S. Tarasov and M. Dyba (Biophysics Resource Core, Structural Biophysics Laboratory, CCR) and H. Bokesch (MTL) for assistance with high-resolution mass spectrometry. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This project was also funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 42 TC 8 Z9 8 U1 6 U2 43 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 29 PY 2015 VL 137 IS 16 BP 5569 EP 5575 DI 10.1021/jacs.5b02156 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA CH3LF UT WOS:000353931500051 PM 25892103 ER PT J AU Cheng, Y Li, J Ito, D Kong, DH Ha, KS Lu, F Wang, B Sattabongkot, J Lim, CS Tsuboi, T Han, ET AF Cheng, Yang Li, Jian Ito, Daisuke Kong, Deok-Hoon Ha, Kwon-Soo Lu, Feng Wang, Bo Sattabongkot, Jetsumon Lim, Chae Seung Tsuboi, Takafumi Han, Eun-Taek TI Antigenicity and immunogenicity of PvRALP1, a novel Plasmodium vivax rhoptry neck protein SO MALARIA JOURNAL LA English DT Article DE Plasmodium vivax; RALP1; Rhoptry neck protein; Antigenicity; Immunogenicity ID MEROZOITE SURFACE PROTEIN-1; VACCINE CANDIDATE ANTIGEN; GLUTAMATE-RICH PROTEIN; G SUBCLASS RESPONSES; FALCIPARUM ANTIGENS; MOVING JUNCTION; BURKINA-FASO; MALARIA; IDENTIFICATION; ANTIBODIES AB Background: Proteins secreted from the rhoptry in Plasmodium merozoites are associated with the formation of tight junctions and parasitophorous vacuoles during invasion of erythrocytes and are sorted within the rhoptry neck or bulb. Very little information has been obtained to date about Plasmodium vivax rhoptry-associated leucine (Leu) zipper-like protein 1 (PvRALP1;PVX_096245), a putative rhoptry protein. PvRALP1 contains a signal peptide, a glycine (Gly)/glutamate (Glu)-rich domain, and a Leu-rich domain, all of which are conserved in other Plasmodium species. Methods: Recombinant PvRALP1s were expressed as full-length protein without the signal peptide (PvRALP1-Ecto) and as truncated protein consisting of the Gly/Glu- and Leu-rich domains (PvRALP1-Tr) using the wheat germ cell-free expression system. The immunoreactivity to these two fragments of recombinant PvRALP1 protein in serum samples from P. vivax-infected patients and immunized mice, including analysis of immunoglobulin G (IgG) subclasses, was evaluated by enzyme-linked immunosorbent assay or protein microarray technology. The subcellular localization of PvRALP1 in blood stage parasites was also determined. Results: Recombinant PvRALP1-Ecto and PvRALP1-Tr proteins were successfully expressed, and in serum samples from P. vivax patients from the Republic of Korea, the observed immunoreactivities to these proteins had 58.9% and 55.4% sensitivity and 95.0% and 92.5% specificity, respectively. The response to PvRALP1 in humans was predominantly cytophilic antibodies (IgG1 and IgG3), but a balanced Th1/Th2 response was observed in mice. Unexpectedly, there was no significant inverse correlation between levels of parasitaemia and levels of antibody against either PvRALP1-Ecto (R-2 = 0.11) or PvRALP1-Tr (R-2 = 0.14) antigens. PvRALP1 was localized in the rhoptry neck of merozoites, and this was the first demonstration of the localization of this protein in P. vivax. Conclusions: This study analysed the antigenicity and immunogenicity of PvRALP1 and suggested that PvRALP1 may be immunogenic in humans during parasite infection and might play an important role during invasion of P. vivax parasites. C1 [Cheng, Yang; Li, Jian; Lu, Feng; Wang, Bo; Han, Eun-Taek] Kangwon Natl Univ, Sch Med, Dept Med Environm Biol & Trop Med, Chunchon 200701, Gangwon Do, South Korea. [Cheng, Yang; Ito, Daisuke] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Li, Jian] Hubei Univ Med, Coll Basic Med, Dept Parasitol, Wuhan 442000, Hubei, Peoples R China. [Ito, Daisuke; Tsuboi, Takafumi] Ehime Univ, Proteo Sci Ctr, Div Malaria Res, Matsuyama, Ehime 7908577, Japan. [Kong, Deok-Hoon; Ha, Kwon-Soo] Kangwon Natl Univ, Sch Med, Dept Mol & Cellular Biochem, Chunchon 200701, Gangwon Do, South Korea. [Lu, Feng] Jiangsu Inst Parasit Dis, Key Lab Parasit Dis Control & Prevent, Minist Hlth, Wuxi, Jiangsu, Peoples R China. [Lu, Feng] Jiangsu Inst Parasit Dis, Jiangsu Prov Key Lab Parasite Mol Biol, Wuxi, Jiangsu, Peoples R China. [Wang, Bo] Anhui Med Univ, Affiliated Hosp 1, Dept Clin Lab, Hefei, Anhui, Peoples R China. [Sattabongkot, Jetsumon] Mahidol Univ, Fac Trop Med, Mahidol Vivax Res Unit, Bangkok 10400, Thailand. [Lim, Chae Seung] Korea Univ, Guru Teg Bahadur Hosp, Coll Med, Dept Lab Med, Seoul 152703, South Korea. RP Tsuboi, T (reprint author), Ehime Univ, Proteo Sci Ctr, Div Malaria Res, Matsuyama, Ehime 7908577, Japan. EM tsuboi.takafumi.mb@ehime-u.ac.jp; ethan@kangwon.ac.kr FU National Research Foundation (NRF) of Korea Grant - Korea government (MEST) [2011-0016401]; Korea Health technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A121180]; MEXT KAKENHI [23117008]; JSPS KAKENHI in japan [23406007] FX This work was supported by National Research Foundation (NRF) of Korea Grant funded by the Korea government (MEST) (2011-0016401) and a grant from the Korea Health technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A121180). This work was also supported in part by MEXT KAKENHI (23117008) and JSPS KAKENHI (23406007) in Japan. NR 46 TC 2 Z9 2 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD APR 29 PY 2015 VL 14 AR 186 DI 10.1186/s12936-015-0698-z PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CI6DA UT WOS:000354847700002 PM 25925592 ER PT J AU Richardson, SP Tinaz, S Chen, R AF Richardson, Sarah Pirio Tinaz, Sule Chen, Robert TI Repetitive Transcranial Magnetic Stimulation in Cervical Dystonia: Effect of Site and Repetition in a Randomized Pilot Trial SO PLOS ONE LA English DT Article ID FOCAL HAND DYSTONIA; PREMOTOR CORTEX; WRITERS CRAMP; BOTULINUM TOXIN; RTMS; TMS AB Dystonia is characterized by abnormal posturing due to sustained muscle contraction, which leads to pain and significant disability. New therapeutic targets are needed in this disorder. The objective of this randomized, sham-controlled, blinded exploratory study is to identify a specific motor system target for non-invasive neuromodulation and to evaluate this target in terms of safety and tolerability in the cervical dystonia (CD) population. Eight CD subjects were given 15-minute sessions of low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (MC), dorsal premotor cortex (dPM), supplementary motor area (SMA), anterior cingulate cortex (ACC) and a sham condition with each session separated by at least two days. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score was rated in a blinded fashion immediately pre- and post-intervention. Secondary outcomes included physiology and tolerability ratings. The mean change in TWSTRS severity score by site was 0.25 +/- 1.7 (ACC), -2.9 +/- 3.4 (dPM), -3.0 +/- 4.8 (MC), -0.5 +/- 1.1 (SHAM), and -1.5 +/- 3.2 (SMA) with negative numbers indicating improvement in symptom control. TWSTRS scores decreased from Session 1 (15.1 +/- 5.1) to Session 5 (11.0 +/- 7.6). The treatment was tolerable and safe. Physiology data were acquired on 6 of 8 subjects and showed no change over time. These results suggest rTMS can modulate CD symptoms. Both dPM and MC are areas to be targeted in further rTMS studies. The improvement in TWSTRS scores over time with multiple rTMS sessions deserves further evaluation. C1 [Richardson, Sarah Pirio] Univ New Mexico, Hlth Sci Ctr, Dept Neurol, Albuquerque, NM 87131 USA. [Tinaz, Sule] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Chen, Robert] Univ Toronto, Toronto Western Res Inst, Toronto, ON, Canada. RP Richardson, SP (reprint author), Univ New Mexico, Hlth Sci Ctr, Dept Neurol, Albuquerque, NM 87131 USA. EM spiriorichardson@salud.unm.edu FU Dystonia Coalition part of the National Institutes of Health (NIH) Rare Disease Clinical Research Network (RDCRN); National Center for Research Resources and National Center for Advancing Translational Science (NCATS) [KL2TR000089, 8UL1TR000041] FX The research was supported by the Dystonia Coalition (Grant Number U54NS065701) which is a part of the National Institutes of Health (NIH) Rare Disease Clinical Research Network (RDCRN), supported through a collaboration between the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), and the National Institute of Neurological Diseases and Stroke (NINDS). This research was also supported (in part or in full) by the National Center for Research Resources and National Center for Advancing Translational Science (NCATS) through Grant Number KL2TR000089 and Grant Number 8UL1TR000041. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 17 TC 1 Z9 1 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 29 PY 2015 VL 10 IS 4 AR e0124937 DI 10.1371/journal.pone.0124937 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH0LO UT WOS:000353711600114 ER PT J AU Hanley, PJ Melenhorst, JJ Nikiforow, S Scheinberg, P Blaney, JW Demmler-Harrison, G Cruz, CR Lam, S Krance, RA Leung, KS Martinez, CA Liu, H Douelc, DC Heslop, HE Rooney, CM Shpall, EJ Barrett, AJ Rodgers, JR Bollard, CM AF Hanley, Patrick J Melenhorst, Jan J Nikiforow, Sarah N Scheinberg, Phillip S Blaney, James W Demmler-Harrison, Gail D Cruz, C. Russell Lam, Sharon Krance, Robert A. Leung, Kathryn S. Martinez, Caridad A. Liu, Hao Douelc, Daniel C. Heslop, Helen E. Rooney, Cliona M. Shpall, Elizabeth J. Barrett, A. John Rodgers, John R. Bollard, Catherine M. TI CMV-specific T cells generated from naive T cells recognize atypical epitopes and may be protective in vivo SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID EPSTEIN-BARR-VIRUS; CELLULAR IMMUNE-RESPONSES; UMBILICAL-CORD BLOOD; VERSUS-HOST-DISEASE; PROPHYLACTIC INFUSION; ADOPTIVE TRANSFER; VIRAL-INFECTIONS; PROTEIN PP65; CYTOMEGALOVIRUS; TRANSPLANTATION AB Adoptive transfer of cytomegalovirus (CMV)-specific T cells derived from adult seropositive donors can effectively restore antiviral immunity after transplantation. However, CMV-seronegative donors lack CMV-specific memory T cells, which restricts the availability of virus-specific T cells for immunoprophylaxis. We demonstrate the feasibility of deriving CMV-specific T cells from naive cells for T cell therapy. Naive T cells primed to recognize CMV were restricted to different, atypical epitopes than T cells derived from CMV-seropositive individuals; however, these two cell populations had similar avidities. CMV-seropositive individuals also had T cells recognizing these atypical epitopes, but these cells had a lower avidity than those derived from the seronegative subjects, which suggests that high-avidity T cells to these epitopes may be lost over time. Indeed, recipients of cord blood (CB) grafts who did not develop CMV were found by clonotypic analysis to have T cells recognizing atypical CMVpp65 epitopes. Therefore, we examined unmanipulated CB units and found that T cells with T cell receptors restricted by atypical epitopes were the most common, which may explain why these T cells expanded. When infused to recipients, naive donor-derived virus-specific T cells that recognized atypical epitopes were associated with prolonged periods of CMV-free survival and complete remission. These data suggest that naive-derived T cells from seronegative patients may be an additional source of cells for CMV immunoprophylaxis. C1 [Hanley, Patrick J; Blaney, James W; Cruz, C. Russell; Lam, Sharon; Krance, Robert A.; Leung, Kathryn S.; Martinez, Caridad A.; Liu, Hao; Heslop, Helen E.; Rooney, Cliona M.; Bollard, Catherine M.] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Hanley, Patrick J; Blaney, James W; Cruz, C. Russell; Lam, Sharon; Krance, Robert A.; Leung, Kathryn S.; Martinez, Caridad A.; Liu, Hao; Heslop, Helen E.; Rooney, Cliona M.; Bollard, Catherine M.] Houston Methodist Hosp, Houston, TX USA. [Hanley, Patrick J; Lam, Sharon; Rooney, Cliona M.; Rodgers, John R.; Bollard, Catherine M.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Hanley, Patrick J; Cruz, C. Russell; Lam, Sharon; Bollard, Catherine M.] George Washington Univ, Program Cell Enhancement & Technol Immunotherapy, Sheikh Zayed Inst Pediat Surg Innovat, Ctr Canc & Immunol Res, Washington, DC 20052 USA. [Hanley, Patrick J; Lam, Sharon; Bollard, Catherine M.] George Washington Univ, Div Blood & Marrow Transplantat, Childrens Natl Hlth Syst, Washington, DC 20052 USA. [Melenhorst, Jan J; Scheinberg, Phillip S; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Nikiforow, Sarah N] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Demmler-Harrison, Gail D; Heslop, Helen E.; Rooney, Cliona M.; Bollard, Catherine M.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Krance, Robert A.; Heslop, Helen E.; Rooney, Cliona M.; Bollard, Catherine M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Douelc, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Rooney, Cliona M.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Shpall, Elizabeth J.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. RP Bollard, CM (reprint author), Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. EM cbollard@cnmc.org FU American Cancer Society [PF-13e046e01-LIB]; Cancer Prevention Research Institute of Texas [RO1 RP100469]; National Cancer Institute [PO1 CA148600e02] FX Funding: This work was supported by a postdoctoral fellowship, PF-13e046e01-LIB, from the American Cancer Society awarded to P.J.H., Cancer Prevention Research Institute of Texas RO1 RP100469 (to C.M.B.), and National Cancer Institute PO1 CA148600e02 (to C.M.B. and E.J.S.) awards. NR 50 TC 8 Z9 8 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 29 PY 2015 VL 7 IS 285 AR 285ra63 DI 10.1126/scitranslmed.aaa2546 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CH1MB UT WOS:000353784700006 PM 25925682 ER PT J AU Navarro, G Quiroz, C Moreno-Delgado, D Sierakowiak, A McDowell, K Moreno, E Rea, W Cai, NS Aguinaga, D Howell, LA Hausch, F Cortes, A Mallol, J Casado, V Lluis, C Canela, EI Ferre, S McCormick, PJ AF Navarro, Gemma Quiroz, Cesar Moreno-Delgado, David Sierakowiak, Adam McDowell, Kimberly Moreno, Estefania Rea, William Cai, Ning-Sheng Aguinaga, David Howell, Lesley A. Hausch, Felix Cortes, Antonio Mallol, Josefa Casado, Vicent Lluis, Carme Canela, Enric I. Ferre, Sergi McCormick, Peter J. TI Orexin-Corticotropin-Releasing Factor Receptor Heteromers in the Ventral Tegmental Area as Targets for Cocaine SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cocaine; CRF receptor; GPCR heteromer; orexin receptor; sigma receptor ID STRESS-INDUCED RELAPSE; PROTEIN-COUPLED RECEPTORS; CRF-BINDING-PROTEIN; SIGMA-1 RECEPTORS; DOPAMINE NEURONS; INDUCED REINSTATEMENT; DRUG SEEKING; OREXIN/HYPOCRETIN; HYPOTHALAMUS; PHARMACOLOGY AB Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R-OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target sigma(1) receptor (sigma R-1) also associates with the CRF1R-OX1R heteromer. Cocaine binding to the sigma R-1-CRF1R-OX1R complex promotes a long-term disruption of the orexin-A-CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking. C1 [Navarro, Gemma; Moreno-Delgado, David; Moreno, Estefania; Aguinaga, David; Cortes, Antonio; Mallol, Josefa; Casado, Vicent; Lluis, Carme; Canela, Enric I.; McCormick, Peter J.] Univ Barcelona, Fac Biol, Ctr Biomed Res Neurodegenerat Dis Network, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain. [Navarro, Gemma; Moreno-Delgado, David; Moreno, Estefania; Aguinaga, David; Cortes, Antonio; Mallol, Josefa; Casado, Vicent; Lluis, Carme; Canela, Enric I.; McCormick, Peter J.] Univ Barcelona, Inst Biomed, E-08028 Barcelona, Spain. [Quiroz, Cesar; Sierakowiak, Adam; McDowell, Kimberly; Rea, William; Cai, Ning-Sheng; Ferre, Sergi] Natl Inst Drug Abuse, Integrat Neurobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Howell, Lesley A.; McCormick, Peter J.] Univ E Anglia, Sch Pharm, Norwich NR4 7TJ, Norfolk, England. [Hausch, Felix] Max Planck Inst Psychiat, D-80804 Munich, Germany. RP Ferre, S (reprint author), NIDA, Integrat Neurobiol Sect, Intramural Res Program, Triad Technol Bldg,333 Cassell Dr, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov; p.mccormick@uea.ac.uk RI Casado, Vicent/K-1660-2014; Ferre, Sergi/K-6115-2014; Canela, Enric I./M-8726-2013; McCormick, Peter/E-7387-2012; OI Ferre, Sergi/0000-0002-1747-1779; Canela, Enric I./0000-0003-4992-7440; McCormick, Peter/0000-0002-2225-5181; Sierakowiak, Adam/0000-0003-2273-2133 FU intramural funds of the National Institute on Drug Abuse; Spanish Ministry of Science and Technology [SAF2011-23813, SAF2009-07276]; Government of Catalonia Grant [2009-SGR-12]; Center for Biomedical Research in Neurodegenerative Diseases Network Grant [CB06/05/0064]; Ramon y Cajal Fellowship FX This work was supported by intramural funds of the National Institute on Drug Abuse, from Spanish Ministry of Science and Technology Grants SAF2011-23813 and SAF2009-07276, Government of Catalonia Grant 2009-SGR-12, and Center for Biomedical Research in Neurodegenerative Diseases Network Grant CB06/05/0064. P.J.M. was supported through a Ramon y Cajal Fellowship. We thank Jasmina Jimenez for technical assistance. NR 43 TC 11 Z9 11 U1 2 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 29 PY 2015 VL 35 IS 17 BP 6639 EP 6653 DI 10.1523/JNEUROSCI.4364-14.2015 PG 15 WC Neurosciences SC Neurosciences & Neurology GA CG9PC UT WOS:000353647600003 PM 25926444 ER PT J AU Delaville, C Mccoy, AJ Gerber, CM Cruz, AV Walters, JR AF Delaville, Claire Mccoy, Alex J. Gerber, Colin M. Cruz, Ana V. Walters, Judith R. TI Subthalamic Nucleus Activity in the Awake Hemiparkinsonian Rat: Relationships with Motor and Cognitive Networks SO JOURNAL OF NEUROSCIENCE LA English DT Article DE beta oscillation; dopamine; gamma oscillations; medial prefrontal cortex; Parkinson's disease; subthalamic nucleus ID DEEP BRAIN-STIMULATION; HUMAN BASAL GANGLIA; MOVEMENT-RELATED CHANGES; HIGH-FREQUENCY ACTIVITY; LOCAL-FIELD POTENTIALS; PARKINSONS-DISEASE; OSCILLATORY ACTIVITY; GAMMA-ACTIVITY; BETA-OSCILLATIONS; CEREBRAL-CORTEX AB Oscillatory activity in both beta and gamma ranges has been recorded in the subthalamic nucleus (STN) of Parkinson's disease (PD) patients and linked to motor function, with beta activity considered antikinetic, and gamma activity, prokinetic. However, the extent to which nonmotor networks contribute to this activity is unclear. This study uses hemiparkinsonian rats performing a treadmill walking task to compare synchronized STN local field potential (LFP) activity with activity in motor cortex (MCx) and medial prefrontal cortex (mPFC), areas involved in motor and cognitive processes, respectively. Data show increases in STN and MCx 29-36 Hz LFP spectral power and coherence after dopamine depletion, which are reduced by apomorphine and levodopa treatments. In contrast, recordings from mPFC3 weeks after dopamine depletion failed to show peaks in 29-36 Hz LFP power. However, mPFC and STN both showed peaks in the 45-55 Hz frequency range in LFP power and coherence during walking before and 21 days after dopamine depletion. Interestingly, power in this low gamma range was transiently reduced in both mPFC and STN after dopamine depletion but recovered by day 21. In contrast to the 45-55 Hz activity, the amplitude of the exaggerated 29-36 Hz rhythm in the STN was modulated by paw movement. Furthermore, as in PD patients, after dopamine treatment a third band (high gamma) emerged in the lesioned hemisphere. The results suggest that STN integrates activity from both motor and cognitive networks in a manner that varies with frequency, behavioral state, and the integrity of the dopamine system. C1 [Delaville, Claire; Mccoy, Alex J.; Gerber, Colin M.; Cruz, Ana V.; Walters, Judith R.] NINDS, Neurophysiol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. RP Walters, JR (reprint author), NINDS, Neurophysiol Pharmacol Sect, NIH, 35 Convent Dr,Bldg 35,Room 1C905, Bethesda, MD 20892 USA. EM waltersj@ninds.nih.gov FU Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH) FX This work was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH). We thank Tom Talbot, Daryl Bandy, and Newlin Morgan in the section of Instrumentation, National Institute of Mental Health-National Institute of Neurological Disorders and Stroke for design and fabrication of the rotary treadmill. NR 64 TC 4 Z9 4 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 29 PY 2015 VL 35 IS 17 BP 6918 EP 6930 DI 10.1523/JNEUROSCI.0587-15.2015 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CG9PC UT WOS:000353647600025 PM 25926466 ER PT J AU Manzourolajdad, A Arnold, J AF Manzourolajdad, Amirhossein Arnold, Jonathan TI Secondary structural entropy in RNA switch (Riboswitch) identification SO BMC BIOINFORMATICS LA English DT Article DE Riboswitch; Entropy; RNA secondary structure; cotH; sucC ID CONTEXT-FREE GRAMMARS; MICROBIAL GENE IDENTIFICATION; MESSENGER-RNA; STRUCTURE PREDICTION; BACILLUS-SUBTILIS; S-ADENOSYLMETHIONINE; LIGAND-BINDING; NONCODING RNA; TRANSCRIPTION TERMINATION; CONFORMATIONAL SELECTION AB Background: RNA regulatory elements play a significant role in gene regulation. Riboswitches, a widespread group of regulatory RNAs, are vital components of many bacterial genomes. These regulatory elements generally function by forming a ligand-induced alternative fold that controls access to ribosome binding sites or other regulatory sites in RNA. Riboswitch-mediated mechanisms are ubiquitous across bacterial genomes. A typical class of riboswitch has its own unique structural and biological complexity, making de novo riboswitch identification a formidable task. Traditionally, riboswitches have been identified through comparative genomics based on sequence and structural homology. The limitations of structural-homology-based approaches, coupled with the assumption that there is a great diversity of undiscovered riboswitches, suggests the need for alternative methods for riboswitch identification, possibly based on features intrinsic to their structure. As of yet, no such reliable method has been proposed. Results: We used structural entropy of riboswitch sequences as a measure of their secondary structural dynamics. Entropy values of a diverse set of riboswitches were compared to that of their mutants, their dinucleotide shuffles, and their reverse complement sequences under different stochastic context-free grammar folding models. Significance of our results was evaluated by comparison to other approaches, such as the base-pairing entropy and energy landscapes dynamics. Classifiers based on structural entropy optimized via sequence and structural features were devised as riboswitch identifiers and tested on Bacillus subtilis, Escherichia coli, and Synechococcus elongatus as an exploration of structural entropy based approaches. The unusually long untranslated region of the cotH in Bacillus subtilis, as well as upstream regions of certain genes, such as the sucC genes were associated with significant structural entropy values in genome-wide examinations. Conclusions: Various tests show that there is in fact a relationship between higher structural entropy and the potential for the RNA sequence to have alternative structures, within the limitations of our methodology. This relationship, though modest, is consistent across various tests. Understanding the behavior of structural entropy as a fairly new feature for RNA conformational dynamics, however, may require extensive exploratory investigation both across RNA sequences and folding models. C1 [Manzourolajdad, Amirhossein; Arnold, Jonathan] Univ Georgia, Inst Bioinformat, Athens, GA 30602 USA. [Manzourolajdad, Amirhossein] NIH, NCBI, Bethesda, MD 20894 USA. [Arnold, Jonathan] Univ Georgia, Dept Genet, Athens, GA 30602 USA. RP Manzourolajdad, A (reprint author), Univ Georgia, Inst Bioinformat, Davison Life Sci Bldg,Room B118B,120 Green St, Athens, GA 30602 USA. EM amanzour@uga.edu FU Georgia Advanced Computing Resource Center (GACRC); NSF [MRI - DBI 0821263]; Intramural Research Program of the NIH, National Library of Medicine FX This work was done under the research assistantship received from the institute of bioinformatics at the University of Georgia. We also would like to acknowledge the The Georgia Advanced Computing Resource Center (GACRC) and the NSF MRI - DBI 0821263 award for the cluster for supporting the work. This research was supported in part by the Intramural Research Program of the NIH, National Library of Medicine. We thank Dr. John L. Spouge for his support. We also thank anonymous reviewers for their time and critical suggestions which were subsequently incorporated in this work. NR 133 TC 6 Z9 6 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD APR 28 PY 2015 VL 16 AR 133 DI 10.1186/s12859-015-0523-2 PG 77 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA CJ2BS UT WOS:000355289800001 PM 25928324 ER PT J AU Monaco, MCG Major, EO AF Monaco, Maria Chiara G. Major, Eugene O. TI Immune system involvement in the pathogenesis of JC virus induced PML: what is learned from studies of patients with underlying diseases and therapies as risk factors SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE progressive multifocal leukoencephalopathy; JCV; immunomodulatory therapy,T cell immune response; multiple sclerosis; natalizumab ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; NATALIZUMAB-TREATED PATIENTS; T-CELL RESPONSES; MULTIPLE-SCLEROSIS; IMMUNOMODULATORY THERAPIES; MAINTENANCE THERAPY; GENE-EXPRESSION; BONE-MARROW; BK VIRUS; REACTIVATION AB The human polyomavirus JC PyV lytic infection of oligodendrocytes in the human brain results in the demyelinating disease progressive multifocal leukoencephalopathy, PML. JCV is a common virus infection in the population that leads to PML in patients with underlying diseases and therapies that cause immune deficiencies or modulate immune system functions. Patients may have high levels of antibody to JCV that neither protect them from PML nor clear the infection once PML is established. Cell-mediated immunity plays a more effective role in clearing initial or reactivated JCV infection before PML occurs. However, patients with underlying diseases and therapies for treatment are at high risk for PML. MS patients on natalizumab are one of the categories with the highest incidence of PML. Natalizumab is a humanized monoclonal antibody targeting alpha 4 integrins that prevents inflammatory cells from entering the brain and it has been used as a treatment for MS. A number of studies have investigated the occurrence of PML in these patients and their cell-mediated immune profile that might gain insight into the mechanism that ties natalizumab with a high risk of developing PML. It seems that cells of the immune system participate in the pathogenesis of PML as well as clearance of JCV infection. C1 [Monaco, Maria Chiara G.; Major, Eugene O.] Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Major, EO (reprint author), Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, NIH, 10 Ctr Dr,Bldg 10,Room 3B14, Bethesda, MD 20892 USA. EM majorg@ninds.nih.gov NR 44 TC 15 Z9 15 U1 1 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD APR 28 PY 2015 VL 6 AR 159 DI 10.3389/fimmu.2015.00159 PG 5 WC Immunology SC Immunology GA CI7IU UT WOS:000354937400001 PM 25972864 ER PT J AU Lai, SJ Huang, ZJ Zhou, H Anders, KL Perkins, TA Yin, WW Li, Y Mu, D Chen, QL Zhang, ZK Qiu, YZ Wang, LP Zhang, HL Zeng, LJ Ren, X Geng, MJ Li, ZJ Tatem, AJ Hay, SI Yu, HJ AF Lai, Shengjie Huang, Zhuojie Zhou, Hang Anders, Katherine L. Perkins, T. Alex Yin, Wenwu Li, Yu Mu, Di Chen, Qiulan Zhang, Zike Qiu, Yanzi Wang, Liping Zhang, Honglong Zeng, Linjia Ren, Xiang Geng, Mengjie Li, Zhongjie Tatem, Andrew J. Hay, Simon I. Yu, Hongjie TI The changing epidemiology of dengue in China, 1990-2014: a descriptive analysis of 25 years of nationwide surveillance data SO BMC MEDICINE LA English DT Article DE Dengue; China; Import; Indigenous; Epidemiology; Outbreak ID REPUBLIC-OF-CHINA; AEDES-ALBOPICTUS; GUANGDONG PROVINCE; VIRUS-INFECTIONS; OUTBREAK; FEVER; TRANSMISSION; REEMERGENCE; EMERGENCE; GUANGZHOU AB Background: Dengue has been a notifiable disease in China since 1 September 1989. Cases have been reported each year during the past 25 years of dramatic socio-economic changes in China, and reached a historical high in 2014. This study describes the changing epidemiology of dengue in China during this period, to identify high-risk areas and seasons and to inform dengue prevention and control activities. Methods: We describe the incidence and distribution of dengue in mainland China using notifiable surveillance data from 1990-2014, which includes classification of imported and indigenous cases from 2005-2014. Results: From 1990-2014, 69,321 cases of dengue including 11 deaths were reported in mainland China, equating to 2.2 cases per one million residents. The highest number was recorded in 2014 (47,056 cases). The number of provinces affected has increased, from a median of three provinces per year (range: 1 to 5 provinces) during 1990-2000 to a median of 14.5 provinces per year (range: 5 to 26 provinces) during 2001-2014. During 2005-2014, imported cases were reported almost every month and 28 provinces (90.3%) were affected. However, 99.8% of indigenous cases occurred between July and November. The regions reporting indigenous cases have expanded from the coastal provinces of southern China and provinces adjacent to Southeast Asia to the central part of China. Dengue virus serotypes 1, 2, 3, and 4 were all detected from 2009-2014. Conclusions: In China, the area affected by dengue has expanded since 2000 and the incidence has increased steadily since 2012, for both imported and indigenous dengue. Surveillance and control strategies should be adjusted to account for these changes, and further research should explore the drivers of these trends. C1 [Lai, Shengjie; Huang, Zhuojie; Zhou, Hang; Yin, Wenwu; Li, Yu; Mu, Di; Chen, Qiulan; Zhang, Zike; Qiu, Yanzi; Wang, Liping; Zhang, Honglong; Zeng, Linjia; Ren, Xiang; Geng, Mengjie; Li, Zhongjie; Yu, Hongjie] Chinese Ctr Dis Control & Prevent, Key Lab Surveillance & Early Warning Infect Dis, Div Infect Dis, Beijing 102206, Peoples R China. [Lai, Shengjie; Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton SO17 1BJ, Hants, England. [Anders, Katherine L.] Univ Oxford, Clin Res Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam. [Anders, Katherine L.] Univ Oxford, Ctr Trop Med, Oxford OX3 7FZ, England. [Anders, Katherine L.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Perkins, T. Alex] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. [Perkins, T. Alex] Univ Notre Dame, Eck Inst Global Hlth, Notre Dame, IN 46556 USA. [Perkins, T. Alex; Tatem, Andrew J.; Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Tatem, Andrew J.] Flowminder Fdn, SE-11355 Stockholm, Sweden. [Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England. RP Yu, HJ (reprint author), Chinese Ctr Dis Control & Prevent, Key Lab Surveillance & Early Warning Infect Dis, Div Infect Dis, 155 Changbai Rd, Beijing 102206, Peoples R China. EM yuhj@chinacdc.cn RI Hay, Simon/F-8967-2015; OI Hay, Simon/0000-0002-0611-7272; ren, xiang/0000-0001-5020-5838 FU Ministry of Science and Technology of China [ZX10004-201, 2014BAI13B05]; Ministry of Health of China [201202006]; China CDC's Key Laboratory of Surveillance and Early-warning on Infectious Disease; National Health and Medical Research Council, Australia [1002608]; Wellcome Trust [084368/Z/07/Z]; NIH/NIAID [U19AI089674]; Bill & Melinda Gates Foundation [OPP110642749446, 1032350]; RAPIDD program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX We thank the staff members at the hospitals, local health departments, and county-, district-, prefecture-, and provincial-level CDCs for their valuable assistance in coordinating data collection.; This work was supported by grants from the Ministry of Science and Technology of China (2012 ZX10004-201, 2014BAI13B05); the Ministry of Health of China (201202006); China CDC's Key Laboratory of Surveillance and Early-warning on Infectious Disease; and the National Health and Medical Research Council, Australia (1002608). KA is supported by the Wellcome Trust (084368/Z/07/Z). AT is supported by funding from NIH/NIAID (U19AI089674) and the Bill & Melinda Gates Foundation (OPP110642749446, 1032350). TP, AT, and SH are supported by the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health.; The sponsor of the study had no role in the study design, data collection, analysis, and interpretation, preparation of the manuscript, or the decision to publish. Dr. Hongjie Yu had full access to all the data in the study and had final responsibility for the decision to submit the manuscript for publication. The views expressed are those of the authors and do not necessarily represent the policy of the China CDC. NR 54 TC 24 Z9 28 U1 0 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD APR 28 PY 2015 VL 13 AR 100 DI 10.1186/s12916-015-0336-1 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CI0KA UT WOS:000354424800001 PM 25925417 ER PT J AU Banga, S Coursen, JD Portugal, S Tran, TM Hancox, L Ongoiba, A Traore, B Doumbo, OK Huang, CY Harty, JT Crompton, PD AF Banga, Simran Coursen, Jill D. Portugal, Silvia Tran, Tuan M. Hancox, Lisa Ongoiba, Aissata Traore, Boubacar Doumbo, Ogobara K. Huang, Chiung-Yu Harty, John T. Crompton, Peter D. TI Impact of Acute Malaria on Pre-Existing Antibodies to Viral and Vaccine Antigens in Mice and Humans SO PLOS ONE LA English DT Article ID MEMORY B-CELLS; PLASMODIUM-FALCIPARUM; SEROLOGICAL MEMORY; HUMORAL IMMUNITY; CHILDREN; ACTIVATION; INFECTION; RESPONSES; DURATION; LIFE AB Vaccine-induced immunity depends on long-lived plasma cells (LLPCs) that maintain antibody levels. A recent mouse study showed that Plasmodium chaubaudi infection reduced pre-existing influenza-specific antibodies-raising concerns that malaria may compromise pre-existing vaccine responses. We extended these findings to P. yoelii infection, observing decreases in antibodies to model antigens in inbred mice and to influenza in outbred mice, associated with LLPC depletion and increased susceptibility to influenza rechallenge. We investigated the implications of these findings in Malian children by measuring vaccine-specific IgG (tetanus, measles, hepatitis B) before and after the malaria-free 6-month dry season, 10 days after the first malaria episode of the malaria season, and after the subsequent dry season. On average, vaccine-specific IgG did not decrease following acute malaria. However, in some children malaria was associated with an accelerated decline in vaccine-specific IgG, underscoring the need to further investigate the impact of malaria on pre-existing vaccine-specific antibodies. C1 [Banga, Simran; Hancox, Lisa; Harty, John T.] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. [Coursen, Jill D.; Portugal, Silvia; Tran, Tuan M.; Crompton, Peter D.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Ongoiba, Aissata; Traore, Boubacar; Doumbo, Ogobara K.] Univ Sci Tech & Technol Bamako, Mali Int Ctr Excellence Res, Bamako, Mali. [Huang, Chiung-Yu] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Div Biostat & Bioinformat, Baltimore, MD USA. [Harty, John T.] Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA. [Harty, John T.] Univ Iowa, Interdisciplinary Grad Program Immunol, Iowa City, IA 52242 USA. RP Harty, JT (reprint author), Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. EM john-harty@uiowa.edu; pcrompton@niaid.nih.gov RI Banga, Simran/L-8806-2013; Crompton, Peter/N-1130-2016 FU National Institutes of Health (NIH) [AI085515, AI095178, AI100527]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH FX Malaria work in the JTH laboratory is supported by National Institutes of Health (NIH) grants (AI085515, AI095178, AI100527). The PDC laboratory and study in Mali is supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 3 Z9 3 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 28 PY 2015 VL 10 IS 4 AR e0125090 DI 10.1371/journal.pone.0125090 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG9SE UT WOS:000353659400072 PM 25919588 ER PT J AU Steck, SE Arab, L Zhang, HM Bensen, JT Fontham, ETH Johnson, CS Mohler, JL Smith, GJ Su, JL Trump, DL Woloszynska-Read, A AF Steck, Susan E. Arab, Lenore Zhang, Hongmei Bensen, Jeannette T. Fontham, Elizabeth T. H. Johnson, Candace S. Mohler, James L. Smith, Gary J. Su, Joseph L. Trump, Donald L. Woloszynska-Read, Anna TI Association between Plasma 25-Hydroxyvitamin D, Ancestry and Aggressive Prostate Cancer among African Americans and European Americans in PCaP SO PLOS ONE LA English DT Article ID D-BINDING-PROTEIN; SERUM VITAMIN-D; UNITED-STATES; PROSPECTIVE COHORT; RACIAL-DIFFERENCES; PREVENTION TRIAL; SUBSEQUENT RISK; D INSUFFICIENCY; BREAST-CANCER; MEN AB Background African Americans (AAs) have lower circulating 25-hydroxyvitamin D3 [25(OH) D3] concentrations and higher prostate cancer (CaP) aggressiveness than other racial/ethnic groups. The purpose of the current study was to examine the relationship between plasma 25(OH) D3, African ancestry and CaP aggressiveness among AAs and European Americans (EAs). Methods Plasma 25(OH) D3 was measured using LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in 537 AA and 663 EA newly-diagnosed CaP patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP) classified as having either 'high' or 'low' aggressive disease based on clinical stage, Gleason grade and prostate specific antigen at diagnosis. Mean plasma 25(OH) D3 concentrations were compared by proportion of African ancestry. Logistic regression was used to calculate multivariable adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for high aggressive CaP by tertile of plasma 25(OH) D3. Results AAs with highest percent African ancestry (>95%) had the lowest mean plasma 25(OH)D3 concentrations. Overall, plasma 25(OH) D3 was associated positively with aggressiveness among AA men, an association that was modified by calcium intake (ORT3vs.T1: 2.23, 95% CI: 1.26-3.95 among men with low calcium intake, and ORT3vs.T1: 0.19, 95% CI: 0.05-0.70 among men with high calcium intake). Among EAs, the point estimates of the ORs were <1.0 for the upper tertiles with CIs that included the null. Conclusions Among AAs, plasma 25(OH)D3 was associated positively with CaP aggressiveness among men with low calcium intake and inversely among men with high calcium intake. The clinical significance of circulating concentrations of 25(OH)D3 and interactions with calcium intake in the AA population warrants further study. C1 [Steck, Susan E.] Univ S Carolina, Arnold Sch Publ Hlth, Canc Prevent & Control Program, Ctr Res Nutr & Hlth Dispar,Dept Epidemiol & Biost, Columbia, SC 29208 USA. [Arab, Lenore] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Zhang, Hongmei] Univ Memphis, Memphis, TN 38152 USA. [Bensen, Jeannette T.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Fontham, Elizabeth T. H.] Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, New Orleans, LA USA. [Johnson, Candace S.; Mohler, James L.; Smith, Gary J.; Trump, Donald L.; Woloszynska-Read, Anna] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Su, Joseph L.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Woloszynska-Read, A (reprint author), Roswell Pk Canc Inst, Buffalo, NY 14263 USA. EM anna.woloszynska-read@roswellpark.org FU United States Department of Defense [11-1-0568, W81WH11-1-0308PCa]; National Institutes of Health [CA067267, CA137650, CA016056] FX United States Department of Defense 11-1-0568 http://cdmrp.army.mil/default.shtml SES, CSJ; United States Department of Defense W81WH11-1-0308PCa http://cdmrp.army.mil/default.shtml AWR; National Institutes of Health CA067267, CA137650 and CA016056 http://www.nih.gov DLT and CSJ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 5 Z9 5 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 28 PY 2015 VL 10 IS 4 AR e0125151 DI 10.1371/journal.pone.0125151 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG9SE UT WOS:000353659400074 PM 25919866 ER PT J AU Stenehjem, JS Kjaerheim, K Bratveit, M Samuelsen, SO Barone-Adesi, F Rothman, N Lan, Q Grimsrud, TK AF Stenehjem, J. S. Kjaerheim, K. Bratveit, M. Samuelsen, S. O. Barone-Adesi, F. Rothman, N. Lan, Q. Grimsrud, T. K. TI Benzene exposure and risk of lymphohaematopoietic cancers in 25 000 offshore oil industry workers SO BRITISH JOURNAL OF CANCER LA English DT Article DE benzene; case-cohort; cancer incidence; lymphohaematopoietic; offshore workers; petroleum industry ID LOW-LEVEL BENZENE; AUSTRALIAN PETROLEUM-INDUSTRY; MULTIPLE-MYELOMA; OCCUPATIONAL-EXPOSURE; LYMPHOMA SUBTYPES; FOLLOW-UP; LEUKEMIA; COHORT; MORTALITY; NORWAY AB Background: The aim of this work was to examine the risk of lymphohaematopoietic (LH) cancer according to benzene exposure among offshore workers. Methods: Cancer registry data were used to identify 112 cancer cases diagnosed during 1999-2011 in a cohort of 24 917 Norwegian men reporting offshore work between 1965 and 1999. Analyses were conducted according to a stratified case-cohort design with a reference subcohort of 1661 workers. Cox regression was used to estimate hazard ratios with 95% confidence intervals, adjusted for other benzene exposure and smoking. Results: Most workers were exposed to benzene for <15 years. The upper range values of average intensity and cumulative exposure were estimated to 0.040 p.p.m. and 0.948 p.p.m.-years, respectively. Risks were consistently elevated among exposed workers for all LH cancers combined and for most subgroups, although case numbers were small and yielded imprecise risk estimates. There was evidence of dose-related risk patterns according to cumulative exposure for acute myeloid leukaemia (AML), multiple myeloma (MM) (P trends 0.052 and 0.024, respectively), and suggestively so for chronic lymphocytic leukaemia (CLL) according to average intensity (P trend 0.094). Conclusions: Our results support an association between cumulative and intensity metrics of low-level benzene exposure and risk for AML, MM, and suggestively for CLL. C1 [Stenehjem, J. S.; Kjaerheim, K.; Grimsrud, T. K.] Canc Registry Norway, Dept Res, N-0304 Oslo, Norway. [Bratveit, M.] Univ Bergen, Dept Global Publ Hlth & Primary Care, N-5020 Bergen, Norway. [Samuelsen, S. O.] Univ Oslo, Dept Math, N-0316 Oslo, Norway. [Barone-Adesi, F.] St George Hosp, Populat Hlth Res Inst, London SW17 0RE, England. [Barone-Adesi, F.] Univ Piemonte Orientale, Dept Pharmaceut Sci, I-28100 Novara, Italy. [Rothman, N.; Lan, Q.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Grimsrud, TK (reprint author), Canc Registry Norway, Dept Res, POB 5313 Majorstuen, N-0304 Oslo, Norway. EM tom.k.grimsrud@kreftregisteret.no OI Kjaerheim, Kristina/0000-0003-0691-3735 FU Research Council of Norway's PETROMAKS program [189612] FX We wish to thank our former Head of Department, Aage Andersen, without whose efforts the establishment of the cohort and the conduct of the subsequent studies would not have been possible, Researcher Leif Age strand for conducting the offshore survey, Senior Consultant Tone Eggen for cleaning the work history data, Data Manager Jan Ivar Martinsen for sampling of the subcohort and linking cancer and exposure estimates to the cohort, and MD Svein Hansen for advice on grouping of LH cancer (Department of Research, Cancer Registry of Norway). We also thank Industrial Hygienists Jorunn Kirkeleit and Bjorg Eli Hollund (Department of Occupational Medicine, Haukeland University Hospital, Norway) and Research Director John Cherrie (Institute of Occupational Medicine, Edinburgh, UK) for assisting with the JEM development. This work was funded by the Research Council of Norway's PETROMAKS program (grant no. 189612). NR 45 TC 3 Z9 3 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD APR 28 PY 2015 VL 112 IS 9 BP 1603 EP 1612 DI 10.1038/bjc.2015.108 PG 10 WC Oncology SC Oncology GA CG9SG UT WOS:000353659800023 PM 25867262 ER PT J AU Kapitonov, VV Koonin, EV AF Kapitonov, Vladimir V. Koonin, Eugene V. TI Evolution of the RAG1-RAG2 locus: both proteins came from the same transposon SO BIOLOGY DIRECT LA English DT Article DE Molecular evolution; genetics; immune system; V(D)J recombination; RAG1 and RAG2 proteins; Transib DNA transposons; Transib transposase ID V(D)J RECOMBINATION; RAG2 PROTEINS; GENES; DATABASE; PERFORMANCE; ELEMENTS; DOMAIN; DNA AB The RAG1 and RAG2 proteins are essential subunits of the V(D)J recombinase that is required for the generation of the enormous variability of antibodies and T-cell receptors in jawed vertebrates. It was demonstrated previously that the 600-aa catalytic core of RAG1 evolved from the transposase of the Transib superfamily transposons. However, although homologs of RAG1 and RAG2 genes are adjacent in the purple sea urchin genome, a transposon encoding both proteins so far has not been reported. Here we describe such transposons in the genomes of green sea urchin, a starfish and an oyster. Comparison of the domain architectures of the RAG1 homologs in these transposons, denoted TransibSU, and other Transib superfamily transposases provides for reconstruction of the structure of the hypothetical TransibVDJ transposon that gave rise to the VDJ recombinases at the onset of vertebrate evolution some 500 million years ago. C1 [Kapitonov, Vladimir V.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Kapitonov, VV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. EM kvladimirv@gmail.com FU US Department of Health and Human Services FX The authors' research is supported by intramural funds of the US Department of Health and Human Services (to the National Library of Medicine). NR 28 TC 16 Z9 16 U1 0 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD APR 28 PY 2015 VL 10 AR 20 DI 10.1186/s13062-015-0055-8 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CG8EJ UT WOS:000353539700001 PM 25928409 ER PT J AU Chung, YW Lagranha, C Chen, Y Sun, JH Tong, G Hockman, SC Ahmad, F Esfahani, SG Bae, DH Polidovitch, N Wu, J Rhee, DK Lee, BS Gucek, M Daniels, MP Brantner, CA Backx, PH Murphy, E Manganiello, VC AF Chung, Youn Wook Lagranha, Claudia Chen, Yong Sun, Junhui Tong, Guang Hockman, Steven C. Ahmad, Faiyaz Esfahani, Shervin G. Bae, Dahae H. Polidovitch, Nazari Wu, Jian Rhee, Dong Keun Lee, Beom Seob Gucek, Marjan Daniels, Mathew P. Brantner, Christine A. Backx, Peter H. Murphy, Elizabeth Manganiello, Vincent C. TI Targeted disruption of PDE3B, but not PDE3A, protects murine heart from ischemia/reperfusion injury SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PDE3B(-/-) mice; protein kinase A; ischemia/reperfusion injury; signalosome; membrane repair ID GLYCOGEN-SYNTHASE KINASE-3-BETA; CA2+-ACTIVATED K+ CHANNELS; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; INNER MITOCHONDRIAL-MEMBRANE; PERMEABILITY TRANSITION PORE; ISCHEMIA-REPERFUSION INJURY; SMOOTH-MUSCLE-CELLS; CARDIAC MYOCYTES; KINASE-A; SIGNAL-TRANSDUCTION AB Although inhibition of cyclic nucleotide phosphodiesterase type 3 (PDE3) has been reported to protect rodent heart against ischemia/reperfusion (I/R) injury, neither the specific PDE3 isoform involved nor the underlying mechanisms have been identified. Targeted disruption of PDE3 subfamily B (PDE3B), but not of PDE3 subfamily A (PDE3A), protected mouse heart from I/R injury in vivo and in vitro, with reduced infarct size and improved cardiac function. The cardioprotective effect in PDE3B(-/-) heart was reversed by blocking cAMP-dependent PKA and by paxilline, an inhibitor of mitochondrial calcium-activated K channels, the opening of which is potentiated by cAMP/PKA signaling. Compared with WT mitochondria, PDE3B(-/-) mitochondria were enriched in antiapoptotic Bcl-2, produced less reactive oxygen species, and more frequently contacted transverse tubules where PDE3B was localized with caveolin-3. Moreover, a PDE3B(-/-) mitochondrial fraction containing connexin-43 and caveolin-3 was more resistant to Ca2+ induced opening of the mitochondrial permeability transition pore. Proteomics analyses indicated that PDE3B(-/-) heart mitochondria fractions were enriched in buoyant ischemia-induced caveolin-3-enriched fractions (ICEFs) containing cardioprotective proteins. Accumulation of proteins into ICEFs was PKA dependent and was achieved by ischemic preconditioning or treatment of WT heart with the PDE3 inhibitor cilostamide. Taken together, these findings indicate that PDE3B deletion confers cardioprotective effects because of cAMP/PKA-induced preconditioning, which is associated with the accumulation of proteins with cardioprotective function in ICEFs. To our knowledge, our study is the first to define a role for PDE3B in cardioprotection against I/R injury and suggests PDE3B as a target for cardiovascular therapies. C1 [Chung, Youn Wook; Hockman, Steven C.; Ahmad, Faiyaz; Rhee, Dong Keun; Manganiello, Vincent C.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Lagranha, Claudia; Sun, Junhui; Tong, Guang; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Chen, Yong; Gucek, Marjan] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. [Esfahani, Shervin G.; Bae, Dahae H.; Daniels, Mathew P.; Brantner, Christine A.] NHLBI, Electron Microscopy Core Facil, NIH, Bethesda, MD 20892 USA. [Chung, Youn Wook; Lee, Beom Seob] Yonsei Univ, Coll Med, Yonsei Cardiovasc Res Inst, Seoul 120752, South Korea. [Tong, Guang] Guangzhou Mil Command, Guangzhou Gen Hosp, Dept Cardiovasc Surg, Guangzhou 510010, Guangdong, Peoples R China. [Polidovitch, Nazari; Wu, Jian; Backx, Peter H.] Univ Toronto, Dept Physiol, Toronto, ON M5S 3A8, Canada. [Polidovitch, Nazari; Wu, Jian; Backx, Peter H.] Univ Toronto, Dept Med, Toronto, ON M5S 3A8, Canada. [Lee, Beom Seob] Yonsei Univ, Grad Program Sci Aging, Seoul 120752, South Korea. [Backx, Peter H.] Univ Hlth Network, Div Cardiol, Toronto, ON M5S 3E2, Canada. RP Chung, YW (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM chungyw@yuhs.ac; manganiv@nhlbi.nih.gov OI Brantner, Christine/0000-0001-8172-901X FU National Heart, Lung, and Blood Institute; Canadian Institutes for Health Research [MOP62954] FX We thank Dr. M. Movsesian of the University of Utah School of Medicine for helpful discussions. Y.W.C., C.L., Y.C., J.S., G.T., S.C.H., F.A., S.G.E., D.H.B., D.K.R., M.G., M.P.D., E.M., and V.C.M. were supported by the National Heart, Lung, and Blood Institute Intramural Research Program. N.P., J.W., and P.H.B. were supported by Canadian Institutes for Health Research Grant MOP62954. NR 73 TC 15 Z9 16 U1 3 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 28 PY 2015 VL 112 IS 17 BP E2253 EP E2262 DI 10.1073/pnas.1416230112 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG8JR UT WOS:000353554000020 PM 25877153 ER PT J AU Smedlund, KB Birnbaumer, L Vazquez, G AF Smedlund, Kathryn B. Birnbaumer, Lutz Vazquez, Guillermo TI Increased size and cellularity of advanced atherosclerotic lesions in mice with endothelial overexpression of the human TRPC3 channel SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TRPC3 channels; atherosclerosis; endothelial inflammation ID ENDOPLASMIC-RETICULUM STRESS; CATION CHANNELS; PLAQUE PROGRESSION; MONOCYTE ADHERENCE; GENE-EXPRESSION; CELLS; VCAM-1; INFLAMMATION; MACROPHAGES; MECHANISMS AB In previous in vitro studies, we showed that Transient Receptor Potential Canonical 3 (TRPC3), a calcium-permeable, nonselective cation channel endowed with high constitutive function, is an obligatory component of the inflammatory signaling that controls expression of the vascular cell adhesion molecule-1 (VCAM-1) and monocyte adhesion to coronary artery endothelial cells. Also, TRPC3 expression in these cells was found to be up-regulated by proatherogenic factors, which enhanced inflammation and VCAM-1 expression. However, it remained to be determined whether these in vitro findings were of relevance to atherosclerotic lesion development in vivo. To answer this important question in the present work, we generated mice with endothelial-specific overexpression of human TRPC3 in an Apoe knockout background (TgEST3ApoeKO) and examined lesions in the aortic sinus following 10 and 16 wk on a high-fat diet. No significant differences were found in size or complexity of early stage lesions (10 wk). However, advanced plaques (16 wk) from TgEST3ApoeKO mice exhibited a significant increase in size and macrophage content compared with nontransgenic littermate controls. Remarkably, this change was correlated with increased VCAM-1 and phospho-IkB alpha immunoreactivity along the endothelial lining of lesions from transgenic animals compared with controls. These findings validate the in vivo relevance of previous in vitro findings and represent, to our knowledge, the first in vivo evidence for a proatherogenic role of endothelial TRPC3. C1 [Smedlund, Kathryn B.; Vazquez, Guillermo] Univ Toledo, Coll Med, Dept Physiol & Pharmacol, Ctr Diabet & Endocrine Res, Toledo, OH 43614 USA. [Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. RP Birnbaumer, L (reprint author), NIEHS, Neurobiol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM birnbau1@niehs.nih.gov; Guillermo.Vazquez@utoledo.edu OI Smedlund, Kathryn/0000-0002-5746-8419 FU NIH [R01HL111877-03, Z01-ES-101864] FX This work was supported by NIH Grant R01HL111877-03 (to G.V.) and in part by the Intramural Research Program of the NIH (Project Z01-ES-101864 to L.B.). NR 37 TC 6 Z9 7 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 28 PY 2015 VL 112 IS 17 BP E2201 EP E2206 DI 10.1073/pnas.1505410112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG8JR UT WOS:000353554000014 PM 25870279 ER PT J AU Baber, JL Louis, JM Clore, GM AF Baber, James L. Louis, John M. Clore, G. Marius TI Dependence of Distance Distributions Derived from Double Electron-Electron Resonance Pulsed EPR Spectroscopy on Pulse-Sequence Time SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE deuteration; distance distributions; EPR spectroscopy; phase memory time; proteins ID SPIN-ECHO; PROTEINS; DYNAMICS; BINDING; SOLIDS; DOMAIN AB Pulsed double electron-electron resonance (DEER) provides pairwise P(r) distance distributions in doubly spin labeled proteins. We report that in protonated proteins, P(r) is dependent on the length of the second echo period T owing to local environmental effects on the spin-label phase memory relaxation time T-m. For the protein ABD, this effect results in a 1.4 a increase in the P(r) maximum from T=6 to 20 mu s. ProteinA has a bimodal P(r) distribution, and the relative height of the shorter distance peak at T=10 mu s, the shortest value required to obtain a reliable P(r), is reduced by 40% relative to that found by extrapolation to T=0. Our results indicate that data at a series of T values are essential for quantitative interpretation of DEER to determine the extent of the T dependence and to extrapolate the results to T=0. Complete deuteration (99%) of the protein was accompanied by a significant increase in T-m and effectively abolished the P(r) dependence on T. C1 [Baber, James L.; Louis, John M.; Clore, G. Marius] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD 20892 USA. RP Baber, JL (reprint author), Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD 20892 USA. EM jamesbaber@niddk.nih.gov; mariusc@mail.nih.gov FU NIDDK, NIH; AIDS Targeted Antiviral Program of the Office of the Director of the NIH FX We thank Alexey Potapov, Ad Bax, and Lalit Deshmukh for useful discussions, and Annie Aniana for technical assistance. This work was supported by the Intramural Program of NIDDK, NIH and by the AIDS Targeted Antiviral Program of the Office of the Director of the NIH (to G.M.C.) NR 20 TC 7 Z9 7 U1 3 U2 18 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1433-7851 EI 1521-3773 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PD APR 27 PY 2015 VL 54 IS 18 BP 5336 EP 5339 DI 10.1002/anie.201500640 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA CH7BW UT WOS:000354191600009 PM 25757985 ER PT J AU Yamada, KM Hall, A AF Yamada, Kenneth M. Hall, Alan TI Reproducibility and cell biology SO JOURNAL OF CELL BIOLOGY LA English DT Editorial Material AB Growing concerns about the reproducibility of published research threaten to undermine the scientific enterprise and erode public trust. Conscientious application of "best practices" for the generation and reporting of research, along with post-publication access to raw data and other research materials, will protect the integrity of the research literature. C1 [Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. [Hall, Alan] Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10065 USA. RP Yamada, KM (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. EM kenneth.yamada@nih.gov; halla@mskcc.org NR 14 TC 3 Z9 3 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD APR 27 PY 2015 VL 209 IS 2 BP 191 EP 193 DI 10.1083/jcb.201503036 PG 3 WC Cell Biology SC Cell Biology GA CH4OM UT WOS:000354012800004 PM 25918221 ER PT J AU Madsen, DH Bugge, TH AF Madsen, Daniel H. Bugge, Thomas H. TI The source of matrix-degrading enzymes in human cancer: Problems of research reproducibility and possible solutions SO JOURNAL OF CELL BIOLOGY LA English DT Editorial Material ID TUMOR-ASSOCIATED MACROPHAGES; EXTRACELLULAR-MATRIX; BREAST-CANCER; DEGRADATION; PROGRESSION; STROMA; CELLS; METALLOPROTEINASES; ANTIBODIES; UROKINASE AB Matrix degradation is central to tumor pathogenesis. Enzymes that degrade extracellular matrix are abundant in tumors. But which out of the complex mixture of cells that form a tumor produces them? Surprisingly, several hundred studies devoted to this question have provided confusion rather than clarity. Our analysis of these studies identifies likely reasons as to why this may be the case, which has implications for the broader issue of research reproducibility. C1 [Madsen, Daniel H.; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Bugge, TH (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov OI Madsen, Daniel Hargboel/0000-0002-3183-6201 FU Intramural NIH HHS NR 32 TC 2 Z9 2 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD APR 27 PY 2015 VL 209 IS 2 BP 195 EP 198 DI 10.1083/jcb.201501034 PG 4 WC Cell Biology SC Cell Biology GA CH4OM UT WOS:000354012800005 PM 25918222 ER PT J AU Zhu, BP Zhang, ZQ Ma, T Yang, XF Li, YX Shung, KK Zhou, QF AF Zhu, Benpeng Zhang, Zhiqiang Ma, Teng Yang, Xiaofei Li, Yongxiang Shung, K. Kirk Zhou, Qifa TI (100)-Textured KNN-based thick film with enhanced piezoelectric property for intravascular ultrasound imaging SO APPLIED PHYSICS LETTERS LA English DT Article ID ELECTRICAL-PROPERTIES; TRANSDUCER AB Using tape-casting technology, 35 mu m free-standing (100)-textured Li doped KNN (KNLN) thick film was prepared by employing NaNbO3 (NN) as template. It exhibited similar piezoelectric behavior to lead containing materials: a longitudinal piezoelectric coefficient (d(33)) of similar to 150 pm/V and an electromechanical coupling coefficient (k(t)) of 0.44. Based on this thick film, a 52 MHz side-looking miniature transducer with a bandwidth of 61.5% at -6 dB was built for Intravascular ultrasound (IVUS) imaging. In comparison with 40 MHz PMN-PT single crystal transducer, the rabbit aorta image had better resolution and higher noise-to-signal ratio, indicating that lead-free (100)-textured KNLN thick film may be suitable for IVUS (>50 MHz) imaging. (C) 2015 AIP Publishing LLC. C1 [Zhu, Benpeng; Yang, Xiaofei] Huazhong Univ Sci & Technol, Sch Opt & Elect Informat, Wuhan 430074, Peoples R China. [Zhang, Zhiqiang; Li, Yongxiang] Chinese Acad Sci, Key Lab Inorgan Funct Mat & Devices, Shanghai 200050, Peoples R China. [Zhu, Benpeng; Ma, Teng; Shung, K. Kirk; Zhou, Qifa] Univ So Calif, Dept Biomed Engn, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. [Zhu, Benpeng] Chinese Acad Sci, State Key Lab Transducer Technol, Shanghai 200050, Peoples R China. RP Zhu, BP (reprint author), Huazhong Univ Sci & Technol, Sch Opt & Elect Informat, Wuhan 430074, Peoples R China. EM benpengzhu@hust.edu.cn; qifazhou@usc.edu FU National Natural Science Foundation of China [61371016, 51172257]; CAS/SAFEA International Partnership Program for Creative Research Teams; Science and Technology Project of Shenzhen [JCYJ20140419131733976]; NIH [R01-EB12058, P41-EB002182] FX This work was supported by National Natural Science Foundation of China (Grant Nos. 61371016 and 51172257), the CAS/SAFEA International Partnership Program for Creative Research Teams, and the Science and Technology Project of Shenzhen (JCYJ20140419131733976), and it was also partially supported by NIH Grant Nos. R01-EB12058 and P41-EB002182. We thank Analytical and Testing Center of Huazhong University of Science & Technology. NR 20 TC 4 Z9 4 U1 5 U2 41 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0003-6951 EI 1077-3118 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD APR 27 PY 2015 VL 106 IS 17 AR 173504 DI 10.1063/1.4919387 PG 4 WC Physics, Applied SC Physics GA CH2ES UT WOS:000353839100060 PM 25991874 ER PT J AU Gonzalez, P Hildesheim, A Herrero, R Katki, H Wacholder, S Porras, C Safaeian, M Jimenez, S Darragh, TM Cortes, B Befano, B Schiffman, M Carvajal, L Palefsky, J Schiller, J Ocampo, R Schussler, J Lowy, D Guillen, D Stoler, MH Quint, W Morales, J Avila, C Rodriguez, AC Kreimer, AR AF Gonzalez, Paula Hildesheim, Allan Herrero, Rolando Katki, Hormuzd Wacholder, Sholom Porras, Carolina Safaeian, Mahboobeh Jimenez, Silvia Darragh, Teresa M. Cortes, Bernal Befano, Brian Schiffman, Mark Carvajal, Loreto Palefsky, Joel Schiller, John Ocampo, Rebeca Schussler, John Lowy, Douglas Guillen, Diego Stoler, Mark H. Quint, Wim Morales, Jorge Avila, Carlos Rodriguez, Ana Cecilia Kreimer, Aimee R. CA Costa Rica HPV Vaccine Trial CVT TI Rationale and design of a long term follow-up study of women who did and did not receive HPV 16/18 vaccination in Guanacaste, Costa Rica SO VACCINE LA English DT Article DE Human papillomavirus; Vaccines; Methods; Long term follow-up ID HPV-16/18 AS04-ADJUVANTED VACCINE; HUMAN-PAPILLOMAVIRUS VACCINATION; BLIND PATRICIA TRIAL; OF-STUDY ANALYSIS; PARTICLE VACCINE; YOUNG-WOMEN; RANDOMIZED-TRIAL; EFFICACY; INFECTION; IMMUNOGENICITY AB The Costa Rica Vaccine Trial (CVT) was a randomized clinical trial conducted between 2004 and 2010, which randomized 7466 women aged 18 to 25 to receive the bivalent HPV-16/18 vaccine or control Hepatitis-A vaccine. Participants were followed for 4 years with cross-over vaccination at the study end. In 2010 the long term follow-up (LTFU) study was initiated to evaluate the 10-year impact of HPV-16/18 vaccination, determinants of the immune response, and HPV natural history in a vaccinated population. Herein, the rationale, design and methods of the LTFU study are described, which actively follows CVT participants in the HPV-arm 6 additional years at biennial intervals (3 additional study visits for 10 years of total follow-up), or more often if clinically indicated. According to the initial commitment, women in the Hepatitis-A arm were offered HPV vaccination at cross-over; they were followed 2 additional years and exited from the study. 92% of eligible CVT women accepted participation in LTFU. To provide underlying rates of HPV acquisition and cervical disease among unvaccinated women to compare with the HPV-arm during LTFU, a new unvaccinated control group (UCG) of women who are beyond the age generally recommended for routine vaccination was enrolled, and will be followed by cervical cancer screening over 6 years. To form the UCG, 5000 women were selected from a local census, of whom 2836 women (61% of eligible women) agreed to participate. Over 90% of participants complied with an interview, blood and cervical specimen collection. Evaluation of comparability between the original (Hepatitis-A arm of CVT) and new (UCG) control groups showed that women's characteristics, as well as their predicted future risk for cervical HPV acquisition, were similar, thus validating use of the UCG. LTFU is poised to comprehensively address many important questions related to long-term effects of prophylactic HPV vaccines. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Gonzalez, Paula; Porras, Carolina; Cortes, Bernal; Carvajal, Loreto; Ocampo, Rebeca; Guillen, Diego; Morales, Jorge; Avila, Carlos; Rodriguez, Ana Cecilia] Proyecto Epidemiol Guanacaste, Fdn INCIENSA, Liberia, Guanacaste, Costa Rica. [Gonzalez, Paula; Herrero, Rolando; Jimenez, Silvia] Int Agcy Res Canc, F-69372 Lyon, France. [Hildesheim, Allan; Katki, Hormuzd; Wacholder, Sholom; Safaeian, Mahboobeh; Schiffman, Mark; Kreimer, Aimee R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Darragh, Teresa M.; Palefsky, Joel] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Befano, Brian; Schussler, John] Informat Management Serv Inc, Calverton, MD USA. [Schiller, John; Lowy, Douglas] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Stoler, Mark H.] Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA. [Quint, Wim] DDL Diagnost Lab, Rijswijk, Netherlands. RP Gonzalez, P (reprint author), Proyecto Epidemiol Guanacaste, Fdn INCIENSA, Solarium 8 C, Liberia, Guanacaste, Costa Rica. EM pgonzalez@proyectoguanacaste.org RI Hildesheim, Allan/B-9760-2015; Kreimer, Aimee/H-1687-2015 OI Hildesheim, Allan/0000-0003-0257-2363; FU NCI [N01-CP-11005]; National Institutes of Health Office of Research on Women's Health FX The Costa Rica HPV Vaccine Trial is a long-standing collaboration between investigators in Costa Rica and the NCI. The trial is sponsored and funded by the NCI (contract N01-CP-11005), with funding support from the National Institutes of Health Office of Research on Women's Health. GlaxoSmithKline Biologicals (GSK) provided vaccine and support for aspects of the trial associated with regulatory submission needs of the company under a Clinical Trials Agreement (FDA BB-IND 7920) during the four-year, randomized blinded phase of our study. The NCI and Costa Rica investigators are responsible for the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation of the manuscript. On efficacy-related manuscripts, GSK has the right to review and comment. Registered with Clinicaltrials.gov NCT00128661 NR 35 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD APR 27 PY 2015 VL 33 IS 18 BP 2141 EP 2151 DI 10.1016/j.vaccine.2015.03.015 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CH0XQ UT WOS:000353746100006 PM 25796338 ER PT J AU Rosati, M Alicea, C Kulkarni, V Virnik, K Hockenbury, M Sardesai, NY Pavlakis, GN Valentin, A Berkower, I Felber, BK AF Rosati, Margherita Alicea, Candido Kulkarni, Viraj Virnik, Konstantin Hockenbury, Max Sardesai, Niranjan Y. Pavlakis, George N. Valentin, Antonio Berkower, Ira Felber, Barbara K. TI Recombinant rubella vectors elicit SIV Gag-specific T cell responses with cytotoxic potential in rhesus macaques SO VACCINE LA English DT Article DE Live attenuated viral vector; Rubella vaccine strain RA27/3; Rhesus macaque; SIV Gag; De nova cellular responses; Recall cellular responses; Memory T cells; Cytotoxic T cells; DNA vaccine; CM9 tetramer response; IFN-gamma response; HIV vaccine; DNA prime rubella boost; Rubella prime boost ID IMMUNODEFICIENCY VIRUS CHALLENGE; HUMORAL IMMUNE-RESPONSES; MEASLES-VACCINE VECTOR; NEUTRALIZING ANTIBODIES; ANKARA RECOMBINANTS; SIVMAC251 CHALLENGE; VIRAL VECTORS; HIV; DNA; ANTIGENS AB Live-attenuated rubella vaccine strain RA27/3 has been demonstrated to be safe and immunogenic in millions of children. The vaccine strain was used to insert SIV gag sequences and the resulting rubella vectors were tested in rhesus macaques alone and together with SIV gag DNA in different vaccine prime-boost combinations. We previously reported that such rubella vectors induce robust and durable SIV-specific humoral immune responses in macaques. Here, we report that recombinant rubella vectors elicit robust de novo SIV-specific cellular immune responses detectable for >10 months even after a single vaccination. The antigen-specific responses induced by the rubella vector include central and effector memory CD4(+) and CD8(+) T cells with cytotoxic potential. Rubella vectors can be administered repeatedly even after vaccination with the rubella vaccine strain RA27/3. Vaccine regimens including rubella vector and Sly gag DNA in different prime-boost combinations resulted in robust long-lasting cellular responses with significant increase of cellular responses upon boost. Rubella vectors provide a potent platform for inducing HIV-specific immunity that can be combined with DNA in a prime-boost regimen to elicit durable cellular immunity. Published by Elsevier Ltd. C1 [Rosati, Margherita; Pavlakis, George N.; Valentin, Antonio] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA. [Alicea, Candido; Kulkarni, Viraj; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA. [Virnik, Konstantin; Hockenbury, Max; Berkower, Ira] US FDA, Immunoregulat Lab, Div Viral Prod, Off Vaccines,Ctr Biol, Silver Spring, MD USA. [Sardesai, Niranjan Y.] Inovio Pharmaceut, Plymouth Meeting, PA USA. RP Berkower, I (reprint author), NCI, Ctr Canc Res, 1050 Boyles St,Bldg 535,Room 209, Frederick, MD 21702 USA. EM ira.berkower@fda.hhs.gov; barbara.felber@nih.gov FU Intramural Research Program of the National Cancer Institute, National Institutes of Health (NCI/NIH) FX This work was supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health (NCI/NIH) (BKF, GNP). NR 49 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD APR 27 PY 2015 VL 33 IS 18 BP 2167 EP 2174 DI 10.1016/j.vaccine.2015.02.067 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CH0XQ UT WOS:000353746100009 PM 25802183 ER PT J AU Blein, S Bardel, C Danjean, V McGuffog, L Healey, S Barrowdale, D Lee, A Dennis, J Kuchenbaecker, KB Soucy, P Terry, MB Chung, WK Goldgar, DE Buys, SS Janavicius, R Tihomirova, L Tung, N Dorfling, CM van Rensburg, EJ Neuhausen, SL Ding, YC Gerdes, AM Ejlertsen, B Nielsen, FC Hansen, TVO Osorio, A Benitez, J Conejero, RA Segota, E Weitzel, JN Thelander, M Peterlongo, P Radice, P Pensotti, V Dolcetti, R Bonanni, B Peissel, B Zaffaroni, D Scuvera, G Manoukian, S Varesco, L Capone, GL Papi, L Ottini, L Yannoukakos, D Konstantopoulou, I Garber, J Hamann, U Donaldson, A Brady, A Brewer, C Foo, C Evans, DG Frost, D Eccles, D Douglas, F Cook, J Adlard, J Barwell, J Walker, L Izatt, L Side, LE Kennedy, MJ Tischkowitz, M Rogers, MT Porteous, ME Morrison, PJ Platte, R Eeles, R Davidson, R Hodgson, S Cole, T Godwin, AK Isaacs, C Claes, K De Leeneer, K Meindl, A Gehrig, A Wappenschmidt, B Sutter, C Engel, C Niederacher, D Steinemann, D Plendl, H Kast, K Rhiem, K Ditsch, N Arnold, N Varon-Mateeva, R Schmutzler, RK Preisler-Adams, S Markov, NB Wang-Gohrke, S de Pauw, A Lefol, C Lasset, C Leroux, D Rouleau, E Damiola, F Dreyfus, H Barjhoux, L Golmard, L Uhrhammer, N Bonadona, V Sornin, V Bignon, YJ Carter, J Van Le, L Piedmonte, M DiSilvestro, PA de la Hoya, M Caldes, T Nevanlinna, H Aittomaki, K Jager, A van den Ouweland, AMW Kets, CM Aalfs, CM van Leeuwen, FE Hogervorst, FBL Meijers-Heijboer, HEJ Oosterwijk, JC van Roozendaal, KEP Rookus, MA Devilee, P van der Luijt, RB Olah, E Diez, O Teule, A Lazaro, C Blanco, I Del Valle, J Jakubowska, A Sukiennicki, G Gronwald, J Lubinski, J Durda, K Jaworska-Bieniek, K Agnarsson, BA Maugard, C Amadori, A Montagna, M Teixeira, MR Spurdle, AB Foulkes, W Olswold, C Lindor, NM Pankratz, VS Szabo, CI Lincoln, A Jacobs, L Corines, M Robson, M Vijai, J Berger, A Fink-Retter, A Singer, CF Rappaport, C Kaulich, DG Pfeiler, G Tea, MK Greene, MH Mai, PL Rennert, G Imyanitov, EN Mulligan, AM Glendon, G Andrulis, IL Tchatchou, S Toland, AE Pedersen, IS Thomassen, M Kruse, TA Jensen, UB Caligo, MA Friedman, E Zidan, J Laitman, Y Lindblom, A Melin, B Arver, B Loman, N Rosenquist, R Olopade, OI Nussbaum, RL Ramus, SJ Nathanson, KL Domchek, SM Rebbeck, TR Arun, BK Mitchell, G Karlan, BY Lester, J Orsulic, S Stoppa-Lyonnet, D Thomas, G Simard, J Couch, FJ Offit, K Easton, DF Chenevix-Trench, G Antoniou, AC Mazoyer, S Phelan, CM Sinilnikova, OM Cox, DG AF Blein, Sophie Bardel, Claire Danjean, Vincent McGuffog, Lesley Healey, Sue Barrowdale, Daniel Lee, Andrew Dennis, Joe Kuchenbaecker, Karoline B. Soucy, Penny Terry, Mary Beth Chung, Wendy K. Goldgar, David E. Buys, Saundra S. Janavicius, Ramunas Tihomirova, Laima Tung, Nadine Dorfling, Cecilia M. van Rensburg, Elizabeth J. Neuhausen, Susan L. Ding, Yuan Chun Gerdes, Anne-Marie Ejlertsen, Bent Nielsen, Finn C. Hansen, Thomas V. O. Osorio, Ana Benitez, Javier Andres Conejero, Raquel Segota, Ena Weitzel, Jeffrey N. Thelander, Margo Peterlongo, Paolo Radice, Paolo Pensotti, Valeria Dolcetti, Riccardo Bonanni, Bernardo Peissel, Bernard Zaffaroni, Daniela Scuvera, Giulietta Manoukian, Siranoush Varesco, Liliana Capone, Gabriele L. Papi, Laura Ottini, Laura Yannoukakos, Drakoulis Konstantopoulou, Irene Garber, Judy Hamann, Ute Donaldson, Alan Brady, Angela Brewer, Carole Foo, Claire Evans, D. Gareth Frost, Debra Eccles, Diana Douglas, Fiona Cook, Jackie Adlard, Julian Barwell, Julian Walker, Lisa Izatt, Louise Side, Lucy E. Kennedy, M. John Tischkowitz, Marc Rogers, Mark T. Porteous, Mary E. Morrison, Patrick J. Platte, Radka Eeles, Ros Davidson, Rosemarie Hodgson, Shirley Cole, Trevor Godwin, Andrew K. Isaacs, Claudine Claes, Kathleen De Leeneer, Kim Meindl, Alfons Gehrig, Andrea Wappenschmidt, Barbara Sutter, Christian Engel, Christoph Niederacher, Dieter Steinemann, Doris Plendl, Hansjoerg Kast, Karin Rhiem, Kerstin Ditsch, Nina Arnold, Norbert Varon-Mateeva, Raymonda Schmutzler, Rita K. Preisler-Adams, Sabine Markov, Nadja Bogdanova Wang-Gohrke, Shan de Pauw, Antoine Lefol, Cedrick Lasset, Christine Leroux, Dominique Rouleau, Etienne Damiola, Francesca Dreyfus, Helene Barjhoux, Laure Golmard, Lisa Uhrhammer, Nancy Bonadona, Valerie Sornin, Valerie Bignon, Yves-Jean Carter, Jonathan Van Le, Linda Piedmonte, Marion DiSilvestro, Paul A. de la Hoya, Miguel Caldes, Trinidad Nevanlinna, Heli Aittomaki, Kristiina Jager, Agnes van den Ouweland, Ans M. W. Kets, Carolien M. Aalfs, Cora M. van Leeuwen, Flora E. Hogervorst, Frans B. L. Meijers-Heijboer, Hanne E. J. Oosterwijk, Jan C. van Roozendaal, Kees E. P. Rookus, Matti A. Devilee, Peter van der Luijt, Rob B. Olah, Edith Diez, Orland Teule, Alex Lazaro, Conxi Blanco, Ignacio Del Valle, Jesus Jakubowska, Anna Sukiennicki, Grzegorz Gronwald, Jacek Lubinski, Jan Durda, Katarzyna Jaworska-Bieniek, Katarzyna Agnarsson, Bjarni A. Maugard, Christine Amadori, Alberto Montagna, Marco Teixeira, Manuel R. Spurdle, Amanda B. Foulkes, William Olswold, Curtis Lindor, Noralane M. Pankratz, Vernon S. Szabo, Csilla I. Lincoln, Anne Jacobs, Lauren Corines, Marina Robson, Mark Vijai, Joseph Berger, Andreas Fink-Retter, Anneliese Singer, Christian F. Rappaport, Christine Kaulich, Daphne Geschwantler Pfeiler, Georg Tea, Muy-Kheng Greene, Mark H. Mai, Phuong L. Rennert, Gad Imyanitov, Evgeny N. Mulligan, Anna Marie Glendon, Gord Andrulis, Irene L. Tchatchou, Sandrine Toland, Amanda Ewart Pedersen, Inge Sokilde Thomassen, Mads Kruse, Torben A. Jensen, Uffe Birk Caligo, Maria A. Friedman, Eitan Zidan, Jamal Laitman, Yael Lindblom, Annika Melin, Beatrice Arver, Brita Loman, Niklas Rosenquist, Richard Olopade, Olufunmilayo I. Nussbaum, Robert L. Ramus, Susan J. Nathanson, Katherine L. Domchek, Susan M. Rebbeck, Timothy R. Arun, Banu K. Mitchell, Gillian Karlan, Beth Y. Lester, Jenny Orsulic, Sandra Stoppa-Lyonnet, Dominique Thomas, Gilles Simard, Jacques Couch, Fergus J. Offit, Kenneth Easton, Douglas F. Chenevix-Trench, Georgia Antoniou, Antonis C. Mazoyer, Sylvie Phelan, Catherine M. Sinilnikova, Olga M. Cox, David G. CA Breast Canc Family Registry EMBRACE GEMO Study Collaborators HEBON TI An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers SO BREAST CANCER RESEARCH LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GENETIC MODIFIERS; OXIDATIVE STRESS; DNA HAPLOGROUPS; SUSCEPTIBILITY; OVARIAN; CONSORTIUM; VARIANTS; MULTIPLE; DISEASES AB Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects. C1 [Blein, Sophie; Damiola, Francesca; Barjhoux, Laure; Sornin, Valerie; Mazoyer, Sylvie; Sinilnikova, Olga M.; Cox, David G.] Univ Lyon 1, Ctr Rech Cancerol Lyon, CNRS, INSERM U1052,UMR5286, F-69365 Lyon, France. [Blein, Sophie; Bardel, Claire; Jager, Agnes; Mazoyer, Sylvie; Sinilnikova, Olga M.; Cox, David G.] Univ Lyon, F-69000 Lyon, France. [Blein, Sophie; Bardel, Claire; Mazoyer, Sylvie; Sinilnikova, Olga M.; Cox, David G.] Univ Lyon 1, F-69100 Villeurbanne, France. [Bardel, Claire; Lasset, Christine; Bonadona, Valerie] Univ Lyon 1, CNRS, Lab Biometrie & Biol Evolut LBBE Biometrie & Bio, UMR 5558, F-69622 Villeurbanne, France. [Danjean, Vincent] Univ Grenoble Alpes, Lab Informat Grenoble LIG, Equipe Projet Multiprogrammat & Ordonnancement Re, UMR 5217, F-38041 Grenoble, France. [Danjean, Vincent] INRIA Rhone Alpes, Equipe Projet MOAIS, F-38334 Saint Ismier, France. [McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Dennis, Joe; Kuchenbaecker, Karoline B.; Easton, Douglas F.; Antoniou, Antonis C.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England. [Healey, Sue; Spurdle, Amanda B.; Chenevix-Trench, Georgia] QIMR Berghofer, Dept Genet & Computat Biol, Brisbane, Qld, Australia. [Soucy, Penny; Simard, Jacques] Univ Laval, Ctr Hosp Univ Quebec, Ctr Rech, Charlesbourg, PQ, Canada. [Terry, Mary Beth] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Chung, Wendy K.] Columbia Univ, Dept Pediat, Coll Phys & Surg, New York, NY 10027 USA. [Chung, Wendy K.] Columbia Univ, Dept Med, Coll Phys & Surg, New York, NY 10027 USA. [Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. [Buys, Saundra S.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Internal Med, Salt Lake City, UT USA. [Breast Canc Family Registry] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA 94538 USA. [Janavicius, Ramunas] Vilnius State Univ, Hosp Santariskiu Clin, Hematol Oncol & Transfus Med Ctr, Vilnius, Lithuania. State Res Inst, Ctr Innovat Med, Dept Mol & Regenerat Med, Vilnius, Lithuania. [Tihomirova, Laima] Latvian Biomed Res & Study Ctr, LV-1067 Riga, Latvia. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Dorfling, Cecilia M.; van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, ZA-0028 Pretoria, South Africa. [Neuhausen, Susan L.; Ding, Yuan Chun] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA. [Gerdes, Anne-Marie] Copenhagen Univ Hosp, Rigshosp, Dept Clin Genet, Copenhagen, Denmark. [Ejlertsen, Bent] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Copenhagen, Denmark. [Nielsen, Finn C.; Hansen, Thomas V. O.] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, Copenhagen, Denmark. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid, Spain. [Osorio, Ana; Benitez, Javier] Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain. [Andres Conejero, Raquel] Hosp Clin Univ Lozano Blesa, Med Oncol Serv, Zaragoza 50009, Spain. [Segota, Ena] Holy Cross Hosp, Michael & Dianne Bienes Comprehens Canc Ctr, Ft Lauderdale, FL USA. [Weitzel, Jeffrey N.; Pensotti, Valeria] City Hope Natl Med Ctr, Clin Canc Genet Community Res Network, Div Clin Canc Genet, Duarte, CA 91010 USA. [Thelander, Margo] John Muir Med Ctr, Walnut Creek, CA USA. [Thelander, Margo] City Hope Natl Med Ctr, Clin Canc Genet Community Res Network, Duarte, CA 91010 USA. [Peterlongo, Paolo] Ist FIRC Oncol Mol IFOM, I-20139 Milan, Italy. [Radice, Paolo] Ist Nazl Tumori, IRCCS, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, I-20133 Milan, Italy. [Pensotti, Valeria] Cogentech Canc Genet Test Lab, I-20139 Milan, Italy. [Dolcetti, Riccardo] Ctr Riferimento Oncol CRO, Canc Bioimmunotherapy Unit, I-33081 Aviano, Italy. [Bonanni, Bernardo; Rennert, Gad] Ist Europeo Oncol, Div Canc Prevent & Genet, I-20141 Milan, Italy. [Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Manoukian, Siranoush] Ist Nazl Tumori, IRCCS, Dept Prevent & Predict Med, Unit Med Genet, I-20133 Milan, Italy. [Varesco, Liliana] Azienda Osped Univ San Martino Genova, IST Ist Nazl Ric Cancro, IRCCS, Dept Epidemiol Prevent & Special Funct,Unit Hered, I-16132 Genoa, Italy. [Capone, Gabriele L.] FiorGen Fdn Pharmacogen, I-50019 Sesto Fiorentino, Italy. [Capone, Gabriele L.; Papi, Laura] Univ Florence, Dept Biomed Expt & Clin Sci, Unit Med Genet, Florence, Italy. Univ Roma La Sapienza, Dept Mol Med, I-00185 Rome, Italy. [Yannoukakos, Drakoulis] Aristotle Univ Thessaloniki, Papageorgiou Hosp, Sch Med, Dept Med Oncol, GR-54006 Thessaloniki, Greece. [Konstantopoulou, Irene] Natl Ctr Sci Res Demokritos, INRASTES, Mol Diagnost Lab, Athens, Greece. Dana Farber Canc Inst, Boston, MA 02215 USA. [Hamann, Ute] Deutsch Krebsforschungszentrum DKFZ, Mol Genet Breast Canc, Heidelberg, Germany. [Donaldson, Alan] St Michaels Hosp, Dept Clin Genet, Bristol BS2 8EG, Avon, England. [Brady, Angela] Kennedy Galton Ctr, North West Thames Reg Genet Serv, Harrow, Middx, England. Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England. [Foo, Claire] Liverpool Womens NHS Fdn Trust, Merseyside & Cheshire Clin Genet Serv, Liverpool L8 7SS, Merseyside, England. Cent Manchester Univ Hosp, NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Genet Med, Manchester, Lancs, England. [Frost, Debra; Platte, Radka; EMBRACE] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge CB1 8RN, England. [Eccles, Diana] Univ Southampton, Southampton Univ Hosp, NHS Trust, Fac Med, Southampton SO16 6YD, Hants, England. [Douglas, Fiona] Newcastle Upon Tyne Hosp, NHS Trust, Int Ctr Life, Inst Human Genet,Northern Genet Serv, Newcastle Upon Tyne NE1 4EP, Tyne & Wear, England. [Cook, Jackie] Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England. [Adlard, Julian] Leeds Teaching Hosp, NHS Trust, Old Med Sch, Yorkshire Reg Genet Serv, Leeds LS1 3EX, W Yorkshire, England. Univ Hosp Leicester, NHS Trust, Leicester Royal Infirm, Dept Clin Genet,Leicestershire Clin Genet Serv, Leicester LE1 5WW, Leics, England. [Walker, Lisa] Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LE, England. [Izatt, Louise] Guys Hosp, Guys & St Thomas NHS Fdn Trust, Clin Genet Serv, London SE1 9RT, England. [Side, Lucy E.; Kennedy, M. John] Great Ormond St Hosp Sick Children, NHS Trust, North East Thames Reg Genet Serv, London WC1N 3BH, England. Trinity Coll Dublin, Acad Unit Clin & Mol Oncol, Dublin 2, Ireland. St James Hosp, Med Oncol Serv, Dublin 8, Ireland. [Tischkowitz, Marc] Cambridge Univ Hosp, Addenbrookes Hosp, NHS Fdn Trust, Addenbrookes Treatment Ctr,Dept Clin Genet,East A, Cambridge CB2 0QQ, England. [Rogers, Mark T.] Univ Wales Hosp, All Wales Med Genet Serv, Cardiff CF14 4XW, S Glam, Wales. [Porteous, Mary E.] Western Gen Hosp, South East Scotland Reg Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland. [Morrison, Patrick J.] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Canc Res & Cell Biol, Belfast BT9 7AE, Antrim, North Ireland. [Morrison, Patrick J.] Belfast City Hosp, Belfast Hlth & Social Care Trust, Dept Med Genet, Belfast BT9 7AB, Antrim, North Ireland. [Eeles, Ros] Inst Canc Res, Oncogenet Team, London SW7 3RP, England. [Eeles, Ros] Royal Marsden NHS Fdn Trust, London SW7 3RP, England. [Davidson, Rosemarie] Yorkhill Hosp, Ferguson Smith Ctr Clin Genet, Glasgow G3 8SJ, Lanark, Scotland. [Hodgson, Shirley] Univ London St Georges Hosp, Dept Med Genet, South West Thames Reg Genet Serv, London SW17 0RE, England. [Cole, Trevor] Birmingham Womens Hosp, Healthcare NHS Trust, West Midlands Reg Genet Serv, Birmingham B15 2TG, W Midlands, England. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA. [Isaacs, Claudine] MedStar Georgetown Univ Hosp, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. 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[Amadori, Alberto] Univ Padua, Dept Surg Sci Oncol & Gastroenterol, Clin Surg 2, I-35124 Padua, Italy. [Amadori, Alberto; Montagna, Marco] IRCCS, IOV, Immunol & Mol Oncol Unit, I-35128 Padua, Italy. [Teixeira, Manuel R.] Portuguese Oncol Inst IPO PORTO, Dept Genet, P-4200072 Oporto, Portugal. [Teixeira, Manuel R.] Univ Porto, ICBAS, P-4050313 Oporto, Portugal. [Foulkes, William] McGill Univ, Dept Human Genet & Oncol, Program Canc Genet, Montreal, PQ J2W 1S6, Canada. [Olswold, Curtis; Pankratz, Vernon S.; Couch, Fergus J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ 85259 USA. [Szabo, Csilla I.] NHGRI, NIH, Bethesda, MD 20892 USA. [Lincoln, Anne; Jacobs, Lauren; Corines, Marina] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10065 USA. [Robson, Mark; Vijai, Joseph; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Clin Genet Res Lab, New York, NY 10065 USA. [Berger, Andreas; Fink-Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng] AKH Wien, Med Univ Vienna, Univ Klin Frauenheilkun, Comprehens Canc Ctr Vienna,Dept Obstet & Gynecol, A-1090 Vienna, Austria. [Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Rennert, Gad] Natl Israeli Canc Control Ctr, IL-34361 Haifa, Israel. [Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, Clalit Hlth Serv, IL-34361 Haifa, Israel. [Rennert, Gad] Technion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med, IL-34362 Haifa, Israel. [Imyanitov, Evgeny N.] NN Petrov Oncol Res Inst, St Petersburg 197758, Russia. [Mulligan, Anna Marie; Andrulis, Irene L.] Univ Toronto, Dept Lab Med & Pathol, Toronto, ON M5S 1A8, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1T8, Canada. [Glendon, Gord] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON M5G 2L7, Canada. [Glendon, Gord; Andrulis, Irene L.; Tchatchou, Sandrine] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Toland, Amanda Ewart] Dept Human Canc Genet, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Ohio State Univ, Wexner Med Ctr, Dept Internal Med, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Ohio State Univ, Wexner Med Ctr, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. Ohio State Univ, Arthur G James Canc Hosp, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Richard J Solove Res Inst OSUCCC James, Columbus, OH 43210 USA. [Pedersen, Inge Sokilde] Aalborg Univ Hosp, Dept Biochem, Sect Mol Diagnost, DK-9000 Aalborg, Denmark. [Thomassen, Mads; Kruse, Torben A.] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark. 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[Olopade, Olufunmilayo I.] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med & Genet, San Francisco, CA 94143 USA. [Ramus, Susan J.] Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. [Nathanson, Katherine L.; Domchek, Susan M.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Div Canc Med, Houston, TX 77230 USA. [Mitchell, Gillian] Peter MacCallum Canc Ctr, Familial Canc Ctr, Sir Peter MacCallum Dept Oncol, East Melbourne, Vic 3002, Australia. [Mitchell, Gillian] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3010, Australia. [Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Stoppa-Lyonnet, Dominique] INSERM, Inst Curie, Serv Genet Oncol, F-75248 Paris, France. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Fac Med, Sorbonne Paris Cite, F-75006 Paris, France. [Thomas, Gilles] Univ Lyon 1, Fac Med Lyon Est, Genet Med, F-69373 Lyon 08, France. [Thomas, Gilles] Ctr Leon Berard, Fdn Synergie Lyon Canc, Inst Natl Canc INCa, F-69008 Lyon 08, France. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Phelan, Catherine M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA. [Sinilnikova, Olga M.] Ctr Leon Berard, Hosp Civils Lyon, Unite Mixte Genet Constitut Canc Frequents, F-69373 Lyon 08, France. [Segota, Ena] City Hope Natl Med Ctr, Clin Canc Genet Community Res Network, Duarte, CA 91010 USA. RP Cox, DG (reprint author), Univ Lyon 1, Ctr Rech Cancerol Lyon, CNRS, INSERM U1052,UMR5286, F-69365 Lyon, France. EM david.cox@lyon.unicancer.fr RI del Valle, Jesus/I-2527-2015; montagna, marco/E-2225-2012; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Dolcetti, Riccardo/O-3832-2015; Teixeira, Manuel/E-4885-2011; Andrulis, Irene/E-7267-2013; Cox, David/A-2023-2009; Gronwald, Jacek/A-4576-2017; manoukian, siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; OI Evans, Gareth/0000-0002-8482-5784; Blanco, Ignacio/0000-0002-7414-7481; Ramus, Susan/0000-0003-0005-7798; Barrowdale, Daniel/0000-0003-1661-3939; del Valle, Jesus/0000-0003-3607-7045; Papi, Laura/0000-0003-4552-9517; Joseph, Vijai/0000-0002-7933-151X; Tommasi, Stefania/0000-0002-2157-2978; Yannoukakos, Drakoulis/0000-0001-7509-3510; VENAT-BOUVET, Laurence/0000-0002-0716-2550; montagna, marco/0000-0002-4929-2150; Dolcetti, Riccardo/0000-0003-1625-9853; Teixeira, Manuel/0000-0002-4896-5982; Cox, David/0000-0002-2152-9259; Gronwald, Jacek/0000-0002-3643-2871; manoukian, siranoush/0000-0002-6034-7562; Peissel, Bernard/0000-0001-9233-3571; Robson, Mark/0000-0002-3109-1692; benitez, javier/0000-0002-0923-7202; Eeles, Rosalind/0000-0002-3698-6241 FU European Commission Seventh Framework Program [223175: HEALTH-F2-2009-223175]; Cancer Research UK [C12292/A11174, C1287/A10118, C1287/A11990, C5047/A8385]; National Health and Medical Research Council (NHMRC) program; National Health and Medical Research Council (NHMRC); American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; Intramural Research Program of the National Cancer Institute, National Institutes of Health; National Cancer Institute, National Institutes of Health [UM1 CA164920]; Lithuania (BFBOCC-LT): Research Council of Lithuania [LIG-07/2012]; LSC [10.0010.08]; European Social Fund [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]; Liepaja City Council, Liepaja, Latvia; Breast Cancer Research Foundation; Cancer Association of South Africa (CANSA); Morris and Horowitz Families Professorship in Cancer Etiology and Outcomes Research; NEYE Foundation; Spanish Association against Cancer (Asociacion Espanola Contra el Cancer) [AECC08]; Thematic Network Cooperative Research in Cancer (Red Tematica Investigacion Cooperativa en Cancer (RTICC), Centro de Investigacion Cancer, Salamanca, Spain) [RTICC 06/0020/1060]; Spanish Ministry of Science and Innovation [FIS PI08 1120]; Fondo de Investigacion Sanitaria (FIS) [SAF2010-20493]; Fundacion Mutua Madrilena (FMMA); City of Hope Clinical Cancer Genetics Community Network and the Hereditary Cancer Research Registry (COH-CCGCRN); National Cancer Institute and the Office of the Director, National Institutes of Health [RC4CA153828]; Italian citizens; Fondazione IRCCS Istituto Nazionale Tumori; Italian Association for Cancer Research (AIRC); European Union (European Social Fund (ESF); Greek national funds through the "Education and Lifelong Learning" operational program of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA; "Heracleitus II: Investing in knowledge society through the European Social Fund"; Deutsches Krebsforschungszentrum (DKFZ); National Institute for Health Research (NIHR) grant to the Biomedical Research Centre, Manchester, UK; NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; Chancellors Distinguished Chair in Biomedical Sciences Professorship; German Cancer Aid [109076]; Center for Molecular Medicine Cologne (CMMC); Ligue National Contre le Cancer; Association "Le cancer du sein, parlons-en!" Award; Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program; GOA [BOF10/GOA/019]; Ghent University Hospital; National Cancer Institute grants to the GOG Administrative Office and Tissue Bank [CA 27469]; GOG Statistical and Data Center [CA 37517]; GOG's Cancer Prevention and Control Committee [CA 101165]; Instituto de Salud Carlos III (ISCIII), Madrid, Spain [RD12/00369/0006, 12/00539]; European Regional Development Fund (Fonds europeen de developpement regional (FEDER)) funds; Helsinki University Central Hospital Research Fund; Academy of Finland [266528]; Finnish Cancer Society; Sigrid Juselius Foundation; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; Netherlands Organization of Scientific Research [NWO 91109024]; Pink Ribbon grant [110005]; Biobanking and Molecular Resource Infrastructure (BBMRI) [NWO 184.021.007/CP46]; Hungarian Research and Technological Innovation Fund (KTIA)/Hungarian Scientific Research Fund (Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA)) [KTIA-OTKA CK-80745, KTIA-OTKA K-112228]; Institut Catala d'Oncologia (ICO): contract grant sponsor: Asociacion Espanola Contra el Cancer; Spanish Health Research Foundation; Ramon Areces Foundation; Instituto de Salud Carlos III (ISCIII); Catalan Health Institute; Autonomous Government of Catalonia; International Hereditary Cancer Center (Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland) [PBZ_KBN_122/P05/2004]; Icelandic Association "Walking for Breast Cancer Research"; Landspitali University Hospital Research Fund; Canadian Institutes of Health Research (CIHR) for the "CIHR Team in Familial Risks of Breast Cancer" program, Canadian Breast Cancer Research Alliance [019511]; Ministry of Economic Development, Innovation and Export Trade [PSR-SIIRI-701]; Ministero della Salute and a "5 x 1,000" Istituto Oncologico Veneto grant; Liga Portuguesa Contra o Cancro; National Breast Cancer Foundation; Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; Cancer Foundation of Western Australia; National Institutes of Health (NIH) through the National Cancer Institute (NCI) [CA 116167, CA 128978, CA 176785]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; US Department of Defense Ovarian Cancer Idea award [W81XWH-10-1-0341]; Ministry of Health of the Czech Republic to Masaryk Memorial Cancer Institute [MMCI 00209805]; European Regional Development Fund; State Budget of the Czech Republic (RECAMO) [CZ. 1.05/2.1.00/03.0101]; Charles University in Prague project [UNCE204024]; Robert and Kate Niehaus Clinical Cancer Genetics Initiative; Intramural Research Program of the National Cancer Institute; Westat, Inc, Rockville, MD, USA [N02-CP-11019-50, N02-CP-65504]; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF), New York, NY, USA; Russian Federation for Basic Research [11-04-00227, 12-04-00928, 12-04-01490]; Federal Agency for Science and Innovations, Russia [02.740.11.0780]; Ohio State University Comprehensive Cancer Center; Istituto Toscano Tumori (ITT); Israeli Inherited Breast Cancer Consortium; Swedish Breast Cancer; Swedish Cancer Society; Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Women's Cancer Research Alliance; University of California, Los Angeles Jonsson Comprehensive Cancer Center Foundation: Breast Cancer Research Foundation; University of California, San Francisco Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center; Cancer Research UK; University of Pennsylvania: National Institutes of Health (NIH) [R01 CA102776, R01 CA083855]; Susan G Komen for the Cure, Basser Center for BRCA; Victorian Familial Cancer Trials Group (VFCTG): Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation; [5U01 CA113916]; [R01 CA140323]; [ISCIIIRETIC RD06/0020/1051]; [PI09/02483]; [PI10/01422]; [PI10/00748]; [PI13/00285]; [PI13/00189 2009SGR290]; [PI13/00189 2009SGR283]; [CA125183]; [R01 CA142996]; [1U01CA161032] FX Higher-level funding: The COGS project is funded through a European Commission Seventh Framework Program grant (agreement number 223175: HEALTH-F2-2009-223175). The CIMBA data management and data analysis were supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. SH is supported by a National Health and Medical Research Council (NHMRC) program grant (to GCT).; Individual researcher support: ACA is a Cancer Research UK Senior Cancer Research Fellow (C12292/A11174). DFE is a Principal Research Fellow of Cancer Research UK. GC, MCS and IC are supported by the National Health and Medical Research Council (NHMRC). BK holds an American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). MHG and PLM were supported by funding from the Intramural Research Program of the National Cancer Institute, National Institutes of Health. OIO is an American Cancer Society Clinical Research Professor. JS is Chairholder of the Canada Research Chair in Oncogenetics.; Funding of constituent studies: The Breast Cancer Family Registry (BCFR) was supported by grant UM1 CA164920 from the National Cancer Institute, National Institutes of Health. The content of this article does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the BCFR. The Baltic Familial Breast Ovarian Cancer Consortium (BFBOCC) is partly supported by Lithuania (BFBOCC-LT): Research Council of Lithuania grant LIG-07/2012; BFBOCC-LV (Latvia) is partly supported by LSC grant 10.0010.08 and in part by a grant from the European Social Fund number 2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016 and the Liepaja City Council, Liepaja, Latvia; Beth Israel Deaconess Medical Center Cancer Center is supported by the Breast Cancer Research Foundation; BRCA-gene mutations and breast cancer in South African women (BMBSA) was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J van Rensburg; SLN (Beckman Research Institute, City of Hope, Duarte, CA, USA) was partially supported by the Morris and Horowitz Families Professorship in Cancer Etiology and Outcomes Research; the Copenhagen Breast Cancer Study (CBCS) was supported by the NEYE Foundation; the Spanish National Cancer Research Center (Centro Nacional de Investigaciones Oncologicas (CNIO)) was partially supported by the Spanish Association against Cancer (Asociacion Espanola Contra el Cancer AECC08), Thematic Network Cooperative Research in Cancer (Red Tematica Investigacion Cooperativa en Cancer (RTICC), Centro de Investigacion Cancer, Salamanca, Spain) RTICC 06/0020/1060, Spanish Ministry of Science and Innovation grants FIS PI08 1120 (Fondo de Investigacion Sanitaria (FIS)) and SAF2010-20493, and the Fundacion Mutua Madrilena (FMMA); the City of Hope Clinical Cancer Genetics Community Network and the Hereditary Cancer Research Registry (COH-CCGCRN), supported in part by award number RC4CA153828 (Principal Investigator: JNW) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; CONsorzio Studi ITaliani sui Tumori Ereditari Alla Mammella, Italy (CONSIT Team): Funds from Italian citizens who allocated the "5 x 1,000" share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (Istituto Nazionale dei Tumori (INT) institutional strategic project "5 x 1,000") (to SM); the Italian Association for Cancer Research (AIRC) (to LO); National Centre for Scientific Research "Demokritos" has been cofinanced by the European Union (European Social Fund (ESF)) and Greek national funds through the "Education and Lifelong Learning" operational program of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA; "Heracleitus II: Investing in knowledge society through the European Social Fund"; the DKFZ study was supported by the Deutsches Krebsforschungszentrum (DKFZ); Epidemiological Study of BRCA1 and BRCA2 Mutation Carriers (EMBRACE) is supported by Cancer Research UK grants C1287/A10118 and C1287/A11990; DGE and FL are supported by a National Institute for Health Research (NIHR) grant to the Biomedical Research Centre, Manchester, UK; the investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London; RE and EB are supported by Cancer Research UK grant C5047/A8385; Kansas University Medical Center: The authors acknowledge support from The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program; AKG was funded by grants 5U01 CA113916 and R01 CA140323 and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship; The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by German Cancer Aid (grant 109076 (to RKS) and by the Center for Molecular Medicine Cologne (CMMC); GC-HBOC is deeply grateful to Dr Sabine Preisler-Adam for providing information and samples; the GEMO Study was supported by the Ligue National Contre le Cancer; the Association "Le cancer du sein, parlons-en!" Award; and the Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program; G-FAST: KDL is supported by GOA grant BOF10/GOA/019 (Ghent University) and spearhead financing of Ghent University Hospital; the Gynecologic Oncology Group (GOG) was supported by National Cancer Institute grants to the GOG Administrative Office and Tissue Bank (grant CA 27469), the GOG Statistical and Data Center (grant CA 37517) and GOG's Cancer Prevention and Control Committee (grant CA 101165); HCSC was supported by grants RD12/00369/0006 and 12/00539 from Instituto de Salud Carlos III (ISCIII), Madrid, Spain, partially supported by European Regional Development Fund (Fonds europeen de developpement regional (FEDER)) funds; the Helsinki Breast Cancer Study (HEBCS) was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation; HEBON is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088 and NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grant 110005 and Biobanking and Molecular Resource Infrastructure (BBMRI) grant NWO 184.021.; 007/CP46; HEBON thanks the registration teams of the Comprehensive Cancer Centre Netherlands and Comprehensive Centre South (together the Netherlands Cancer Registry) and PALGA (Dutch Pathology Registry) for part of the data collection; the High Risk Breast Cancer Program (HRBCP) is supported by the Hong Kong Hereditary Breast Cancer Family Registry and the Dr Ellen Li Charitable Foundation, Hong Kong; the Hungarian Breast and Ovarian Cancer Study (HUNBOCS) was supported by Hungarian Research and Technological Innovation Fund (KTIA)/Hungarian Scientific Research Fund (Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA)) research grants KTIA-OTKA CK-80745 and KTIA-OTKA K-112228; Institut Catala d'Oncologia (ICO): contract grant sponsor: Asociacion Espanola Contra el Cancer; Spanish Health Research Foundation; Ramon Areces Foundation; Instituto de Salud Carlos III (ISCIII); Catalan Health Institute; and Autonomous Government of Catalonia; contract grant numbers ISCIIIRETIC RD06/0020/1051, PI09/02483, PI10/01422, PI10/00748, PI13/00285, PI13/00189 2009SGR290 and PI13/00189 2009SGR283; the International Hereditary Cancer Center (Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland) was supported by grant PBZ_KBN_122/P05/2004; Landspitali - The National University Hospital of Iceland was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund; the Interdisciplinary Health Research Internal Team Breast Cancer Susceptibility Study (INHERIT) was supported by the Canadian Institutes of Health Research (CIHR) for the "CIHR Team in Familial Risks of Breast Cancer" program, Canadian Breast Cancer Research Alliance grant 019511 and Ministry of Economic Development, Innovation and Export Trade grant PSR-SIIRI-701; the Istituto Oncologico Veneto Hereditary Breast and Ovarian Cancer Study (IOVHBOCS) is supported by the Ministero della Salute and a "5 x 1,000" Istituto Oncologico Veneto grant; the Portuguese Oncology Institute-Porto Breast Cancer Study (IPOBCS) was supported in part by Liga Portuguesa Contra o Cancro; kConFab is supported by a grant from the National Breast Cancer Foundation and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia; the Mayo Clinic is supported by National Institutes of Health (NIH) grants CA 116167, CA 128978 and CA 176785 through the National Cancer Institute (NCI), an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a US Department of Defense Ovarian Cancer Idea award (W81XWH-10-1-0341), a grant from the Breast Cancer Research Foundation, a generous gift from the David F and Margaret T Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation; McGill University Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade; Modifier Study of Quantitative Effects on Disease (ModSQuaD) was supported by the Ministry of Health of the Czech Republic to Masaryk Memorial Cancer Institute (MH CZ - DRO) (MMCI 00209805) and by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ. 1.05/2.1.00/03.; 0101) (to LF), and by Charles University in Prague project UNCE204024 (MZ); Memorial Sloan Kettering Cancer Center (MSKCC) is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative; National Cancer Institute, National Institutes of Health: The research of MHG and PLM was supported by the Intramural Research Program of the National Cancer Institute and by support services contracts N02-CP-11019-50 and N02-CP-65504 with Westat, Inc, Rockville, MD, USA; the National Israeli Cancer Control Center (NICCC) is supported by Clalit Health Services in Israel; some of its activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), New York, NY, USA; NN Petrov Institute of Oncology has been supported by the Russian Federation for Basic Research (grants 11-04-00227, 12-04-00928 and 12-04-01490) and the Federal Agency for Science and Innovations, Russia (contract 02.740.11.0780); The Ohio State University Clinical Cancer Genetics (OSUCCG) is supported by The Ohio State University Comprehensive Cancer Center; the Pisa Breast Cancer Study (PBCS) was supported by Istituto Toscano Tumori (ITT) grants 2011-2013; Sheba Medical Center was partially funded through a grant from the Israel Cancer Association and funding for the Israeli Inherited Breast Cancer Consortium; the Swedish Breast Cancer Study collaborators are supported by the Swedish Cancer Society; The University of Chicago is supported by NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996 and 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance and the Breast Cancer Research Foundation; University of California, Los Angeles Jonsson Comprehensive Cancer Center Foundation: Breast Cancer Research Foundation; University of California, San Francisco Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center; UK Familial Ovarian Cancer Registry (UKFOCR) was supported by a project grant from Cancer Research UK (to Paul DP Pharoah); the University of Pennsylvania: National Institutes of Health (NIH) grants R01 CA102776 and R01 CA083855; the Breast Cancer Research Foundation; the Susan G Komen for the Cure, Basser Center for BRCA; Victorian Familial Cancer Trials Group (VFCTG): Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation; The Women's Cancer Program (WCP) at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). NR 54 TC 3 Z9 3 U1 7 U2 33 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. PD APR 25 PY 2015 VL 17 AR 61 DI 10.1186/s13058-015-0567-2 PG 15 WC Oncology SC Oncology GA CL2KV UT WOS:000356773600001 PM 25925750 ER PT J AU Guo, B Fang, ZZ Yang, L Xiao, L Xia, YL Gonzalez, FJ Zhu, LL Cao, YF Ge, GB Yang, L Sun, HZ AF Guo, Bin Fang, Zhongze Yang, Lu Xiao, Ling Xia, Yangliu Gonzalez, Frank J. Zhu, Liangliang Cao, Yunfeng Ge, Guangbo Yang, Ling Sun, Hongzhi TI Tissue and species differences in the glucuronidation of glabridin with UDP-glucuronosyltransferases SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE Glabridin; Glucuronidation; UDP-glucuronosyltransferases; Species differences ID TANDEM MASS-SPECTROMETRY; MESSENGER-RNA EXPRESSION; ISOFLAVAN GLABRIDIN; CYNOMOLGUS MONKEY; 1A ISOFORMS; INHIBITION; ENZYMES; LIVER; SELECTIVITY; ABSORPTION AB Glabridin (GA) has gained wide application in the cosmetics and food industry. This study was performed to investigate its metabolic inactivation and elimination by glucuronidation by use of liver and intestine microsomes from humans (HLM and HIM) and rats (RLM and RIM), and liver microsomes from cynomolgus monkeys and beagle dogs (CyLM and DLM). Both hydroxyl groups at the C2 and C4 positions of the B ring are conjugated to generate two mono-glucuronides (M1 and M2). HIM, RIM and RLM showed the most robust activity in catalyzing M2 formation with intrinsic clearance values (Cl-int) above 2000 mu L/min/mg, with little measurable M1 formation activity. DLM displayed considerable activity both in M1 and M2 formation, with Cl-int values of 71 and 214 mu L/min/mg, respectively, while HLM and CyLM exhibited low activities in catalyzing M1 and M2 formation, with Cl-int values all below 20 mu L/min/mg. It is revealed that UGT1A1, 1A3, 1A9, 2B7, 2B15 and extrahepatic UGT1A8 and 1A10 are involved in GA glucuronidation. Nearly all UGTs preferred M2 formation except for UGT1A1. Notably, UGT1A8 displayed the highest activity with a Cl-int value more than 5-fold higher than the other isoforms. Chemical inhibition studies, using selective inhibitors of UGT1A1, 1A9, 2B7 and 1A8, further revealed that UGT1A8 contributed significantly to intestinal GA glucuronidation in humans. In summary, this in vitro study demonstrated large species differences in GA glucuronidation by liver and intestinal microsomes, and that intestinal UGTs are important for the pathway in humans. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Guo, Bin; Sun, Hongzhi] Liaoning Med Univ, Affiliated Hosp 1, Jinzhou, Peoples R China. [Fang, Zhongze] Tianjin Med Univ, Sch Publ Hlth, Dept Toxicol, Tianjin, Peoples R China. [Guo, Bin; Fang, Zhongze; Yang, Lu; Cao, Yunfeng] Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian, Peoples R China. [Guo, Bin; Fang, Zhongze; Yang, Lu; Cao, Yunfeng] Liaoning Med Univ, Affiliated Hosp 1, Dalian, Peoples R China. [Xiao, Ling; Zhu, Liangliang] Anqing Normal Univ, Sch Life Sci, Ctr Drug & Food Safety Evaluat, Anqing 246011, Peoples R China. [Xia, Yangliu; Ge, Guangbo; Yang, Ling] Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China. [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cao, Yunfeng] Shanghai Inst Planned Parenthood Res, Shanghai Engineer & Technol Res Ctr Reprod Hlth D, Key Lab Contracept & Devices Res NPFPC, Shanghai, Peoples R China. RP Zhu, LL (reprint author), Anqing Normal Univ, Sch Life Sci, Ctr Drug & Food Safety Evaluat, 128 Linghu South Rd, Anqing 246011, Peoples R China. EM binguo_ln@163.com; zhull_better@163.com FU Startup Project of Doctorial Scientific Research; Anqing Normal University [K05000130011]; Natural Science Foundation of Anhui Educational Commission [AQKJ2014B007]; 973 Program [2013CB531800] FX The authors thank the Startup Project of Doctorial Scientific Research, Anqing Normal University (K05000130011), Natural Science Foundation of Anhui Educational Commission (AQKJ2014B007) and the 973 Program (2013CB531800) for their support of this work. NR 29 TC 4 Z9 5 U1 2 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 EI 1872-7786 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD APR 25 PY 2015 VL 231 BP 90 EP 97 DI 10.1016/j.cbi.2015.03.001 PG 8 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA CH0VS UT WOS:000353741100011 PM 25765239 ER PT J AU Spong, C AF Spong, Cathy TI Project placenta SO NEW SCIENTIST LA English DT Editorial Material C1 US NIH, Human Placenta Project, Bethesda, MD 20892 USA. RP Spong, C (reprint author), US NIH, Human Placenta Project, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU REED BUSINESS INFORMATION LTD PI SUTTON PA QUADRANT HOUSE THE QUADRANT, SUTTON SM2 5AS, SURREY, ENGLAND SN 0262-4079 J9 NEW SCI JI New Sci. PD APR 25 PY 2015 VL 226 IS 3018 BP 29 EP 29 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH2PQ UT WOS:000353867500015 ER PT J AU Yutin, N Kapitonov, VV Koonin, EV AF Yutin, Natalya Kapitonov, Vladimir V. Koonin, Eugene V. TI A new family of hybrid virophages from an animal gut metagenome SO BIOLOGY DIRECT LA English DT Article ID DNA VIRUSES; EVOLUTION; TRANSPOSONS; EUKARYOTES; ORIGIN; RECOMBINATION; TRANSPOVIRONS; ENVIRONMENT; SUGGESTS; SPUTNIK AB Search of metagenomics sequence databases for homologs of virophage capsid proteins resulted in the discovery of a new family of virophages in the sheep rumen metagenome. The genomes of the rumen virophages (RVP) encode a typical virophage major capsid protein, ATPase and protease combined with a Polinton-type, protein primed family B DNA polymerase. The RVP genomes appear to be linear molecules, with terminal inverted repeats. Thus, the RVP seem to represent virophage-Polinton hybrids that are likely capable of formation of infectious virions. Virion proteins of mimiviruses were detected in the same metagenomes as the RVP suggesting that the virophages of the new family parasitize on giant viruses that infect protist inhabitants of the rumen. C1 [Yutin, Natalya; Kapitonov, Vladimir V.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU US Department of Health and Human Services FX The authors' research is supported by intramural funds of the US Department of Health and Human Services (to the National Library of Medicine). NR 36 TC 11 Z9 11 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD APR 25 PY 2015 VL 10 AR 19 DI 10.1186/s13062-015-0054-9 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CG8EG UT WOS:000353539400002 PM 25909276 ER PT J AU Gonzalez-Calixto, C Cazares-Raga, FE Cortes-Martinez, L del Angel, RM Medina-Ramirez, F Mosso, C Ocadiz-Ruiz, R Valenzuela, JG Rodriguez, MH Hernandez-Hernandez, FD AF Gonzalez-Calixto, Cecilia Cazares-Raga, Febe E. Cortes-Martinez, Leticia Maria del Angel, Rosa Medina-Ramirez, Fernando Mosso, Clemente Ocadiz-Ruiz, Ramon Valenzuela, Jesus G. Henry Rodriguez, Mario de la Cruz Hernandez-Hernandez, Fidel TI AealRACK1 expression and localization in response to stress in C6/36 HT mosquito cells SO JOURNAL OF PROTEOMICS LA English DT Article DE C6/36 HT cells; Receptor for Activated C; Kinase (RACK1); Scaffold protein; Stress conditions; Aedes mosquito ID O-GLCNAC MODIFICATION; PROTEIN-KINASE-C; G-BETA-GAMMA; AEDES-ALBOPICTUS; DENGUE-VIRUS; SCAFFOLD PROTEIN; RACK1 FUNCTION; CRYO-EM; RECEPTOR; ARABIDOPSIS AB The Receptor for Activated C kinase 1 (RACK1), a scaffold protein member of the tryptophanaspartate (WD) repeat family, folds in a seven-bladed 3-propeller structure that permits the association of proteins to form active complexes. Mosquitoes of the genus Aedes sp., are vectors of virus producing important diseases such as: dengue, chilcungunya and yellow fever. Based on the highly conserved gene sequence of AeaeRACK1 of the mosquito Aedes aegypti we characterized the mRNA and protein of the homologous AealRACK1 from the Ae. alloopictusderived cell line C6/36 HT. Two protein species differing in MW/pI values were observed at 35 kDa/8.0 and 36 IrDa/6.5. The behavior of AealRACK1 was studied inducing stress with serum deprivation and the glucocorticoid dexamethasone. Both stressors induced increase of the expression of AealRACK1 mRNA and proteins. In serum-deprived cells AealRACK1 protein was located cortically near the plasma membrane in contrast to dexamethasone-treated cells where the protein formed a dotted pattern in the cytoplasm. In addition, 33 protein partners were identified by immunoprecipitation and mass spectrometry. Most of the identified proteins were ribosomal, involved in signaling pathways and stress responses. Our results suggest that AealRACK1 in C6/36 FIT cells respond to stress increasing its synthesis and producing phosphorylated activated form. Biological significance Insect cells adapt to numerous environmental stressors, including chemicals and invasion of pathogenic microorganisms among others, coordinating cellular and organismal responses. Individual cells sense the environment using receptors that trigger signaling pathways that regulate expression of specific effector proteins and/or cellular responses as movement or secretion. In the coordination of responses to stress, scaffold proteins are pivotal molecules that recruit other proteins forming active complexes. The Receptor for Activated C Kinase 1 (RACK1) is the best studied member of the conserved tryptophan-aspartate (WD) repeat family. RACK1 folds in a seven-bladed p-propeller structure and it could be activated during stress, participating in different signaling pathways. The presence and activities of RACK1 in mosquitoes had not been documented before, in this work the molecule is demonstrated in an Aedes albopictus-derived cell line and its reaction to stress is observed under the effect of serum deprivation and the presence of glucocorticoid analog dexamethasone, a chemical used to cause stress in vitro. (C) 2014 Elsevier B.V. All rights reserved. C1 [Gonzalez-Calixto, Cecilia; Cazares-Raga, Febe E.; Cortes-Martinez, Leticia; Maria del Angel, Rosa; Medina-Ramirez, Fernando; Mosso, Clemente; Ocadiz-Ruiz, Ramon; de la Cruz Hernandez-Hernandez, Fidel] IPN, Ctr Invest & Estudios Avanzados, Dept Infectom & Patogenesis Mol, Mexico City 07360, DF, Mexico. [Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Henry Rodriguez, Mario] Inst Nacl Salud Publ, Ctr Invest Sobre Enfermedades Infecciosas, Cuernavaca, Morelos, Mexico. RP Hernandez-Hernandez, FD (reprint author), IPN, Ctr Invest & Estudios Avanzados, Dept Infectom & Patogenesis Mol, Av Inst Politecn Nacl 2508, Mexico City 07360, DF, Mexico. EM cruzcruz@cinvestav.mx RI Hernandez-Hernandez, Fidel/I-5193-2012; OI Hernandez-Hernandez, Fidel/0000-0002-7276-7513; del Angel, Rosa/0000-0002-6785-2035 FU CONACyT, Mexico [202753]; CONACYT [83866, 180514]; ICyTDF [PIFUTP09-298]; Fundacion Miguel Aleman A. C. [19]; Universidad Simon Bolivar Mexico FX We thank J. Garcia Jimenez and J. M. Ceballos Ramirez, for their technical assistance; to Abel Trujillo Ocampo M.Sc. and Javier Cezares Apatiga M.Sc by their advice, Departamento de InfectOmica y Patogenesis Molecular, CINVESTAV-IPN, Mexico. Cecilia Gonzalez Calixto received a PhD scholarship from CONACyT, Mexico (No. 202753). We are grateful for the financial support from CONACYT (Projects No. 83866 and No. 180514), ICyTDF (PIFUTP09-298), Fundacion Miguel Aleman A. C. (Grant 2012 #19) and Universidad Simon Bolivar Mexico (Grant 2012 to FCHH). Funding agencies did not participate in any part of the study design, writing of the report or the decision to submit the paper for publication. NR 78 TC 1 Z9 1 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-3919 EI 1876-7737 J9 J PROTEOMICS JI J. Proteomics PD APR 24 PY 2015 VL 119 BP 45 EP 60 DI 10.1016/j.jprot.2014.11.019 PG 16 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CH9GN UT WOS:000354344100005 PM 25555378 ER PT J AU Brown, P Ritchie, D Ironside, J Abee, C Kreil, T Gibson, S AF Brown, Paul Ritchie, Diane Ironside, James Abee, Christian Kreil, Thomas Gibson, Susan TI Blood transmission of prion infectivity in the squirrel monkey: The Baxter study SO PRION LA English DT Meeting Abstract C1 [Brown, Paul] NIH, Bethesda, MD 20892 USA. [Ritchie, Diane; Ironside, James] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Abee, Christian] Univ Texas, Bastrop, TX USA. [Kreil, Thomas] Baxter Biosci, Vienna, Austria. [Gibson, Susan] Univ S Alabama, Mobile, AL 36688 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA P.164 BP S98 EP S98 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900182 ER PT J AU Brown, P Farrell, M AF Brown, Paul Farrell, Michael TI A practical approach to avoiding iatrogenic CJD from invasive instruments SO PRION LA English DT Meeting Abstract C1 [Brown, Paul] NIH, Bethesda, MD 20892 USA. [Farrell, Michael] Beaumont Hosp, Dublin, Ireland. NR 0 TC 0 Z9 0 U1 2 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA P.163 BP S98 EP S98 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900181 ER PT J AU Chesebro, B Striebel, J Rangel, A Phillips, K Hughson, A Caughey, B Race, B AF Chesebro, Bruce Striebel, James Rangel, Alejandra Phillips, Katie Hughson, Andrew Caughey, Byron Race, Brent TI Role of brain interstitial fluid flow in very early generation and spread of PrPres after microinjection of prion infectivity in C57BL mouse brain SO PRION LA English DT Meeting Abstract C1 [Chesebro, Bruce; Striebel, James; Rangel, Alejandra; Phillips, Katie; Hughson, Andrew; Caughey, Byron; Race, Brent] NIAID, Rocky Mt Lab, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA O.03 BP S2 EP S2 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900004 ER PT J AU Edskes, H Wickner, R AF Edskes, Herman Wickner, Reed TI Sporadic distribution of prion-forming ability of Sup35p and Ure2p from yeasts and fungi SO PRION LA English DT Meeting Abstract C1 [Edskes, Herman; Wickner, Reed] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA P.41 BP S33 EP S33 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900059 ER PT J AU Greene, L Yim, YI Park, BC Yadavalli, R Zhao, XH Eisenberg, E AF Greene, Lois Yim, Yang-in Park, Bum-chan Yadavalli, Rajgopal Zhao, Xiaohong Eisenberg, Evan TI The multivesicular body is the major internal site of prion conversion SO PRION LA English DT Meeting Abstract C1 [Greene, Lois; Yim, Yang-in; Park, Bum-chan; Yadavalli, Rajgopal; Zhao, Xiaohong; Eisenberg, Evan] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA P.117 BP S72 EP S73 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900135 ER PT J AU Groveman, BR Orru, CD Hughson, AG Zanusso, G Pocchiari, M Coulthart, MB Caughey, B AF Groveman, Bradley R. Orru, Christina D. Hughson, Andrew G. Zanusso, Gianluigi Pocchiari, Maurizio Coulthart, Michael B. Caughey, Byron TI An improved test for the detection of Creutzfeldt-Jakob Disease from human CSF using new RT-QuIC conditions SO PRION LA English DT Meeting Abstract C1 [Groveman, Bradley R.; Orru, Christina D.; Hughson, Andrew G.; Caughey, Byron] NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT USA. [Zanusso, Gianluigi] Univ Verona, Dept Neurol & Movement Sci, I-37100 Verona, Italy. [Pocchiari, Maurizio] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. [Coulthart, Michael B.] Publ Hlth Agcy Canada, Canadian CJD Surveillance Syst, Ottawa, ON, Canada. NR 0 TC 0 Z9 0 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA P.23 BP S23 EP S23 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900041 ER PT J AU Hughson, A Orru, C Groveman, B Campbell, K Caughey, B AF Hughson, Andrew Orru, Christina Groveman, Bradley Campbell, Katrina Caughey, Byron TI Factors that improve RT-QuIC detection of prion seeding activity SO PRION LA English DT Meeting Abstract C1 [Hughson, Andrew; Orru, Christina; Groveman, Bradley; Campbell, Katrina; Caughey, Byron] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA P.56 BP S40 EP S41 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900074 ER PT J AU Kraus, A Groveman, BR Anson, KJ Raymond, L Dorward, DW Hughson, A Caughey, B AF Kraus, Allison Groveman, Bradley R. Anson, Kelsie J. Raymond, Lynne Dorward, David W. Hughson, Andrew Caughey, Byron TI Ultrastructural and biochemical analyses of prion protein amyloids and the role of lysine and proline residues in amyloid formation SO PRION LA English DT Meeting Abstract C1 [Kraus, Allison; Groveman, Bradley R.; Anson, Kelsie J.; Raymond, Lynne; Dorward, David W.; Hughson, Andrew; Caughey, Byron] NIH, Rocky Mt Labs, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA P.126 BP S77 EP S77 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900144 ER PT J AU Manca, M Zanusso, G Caughey, B AF Manca, Matteo Zanusso, Gianluigi Caughey, Byron TI Detection of sCJD prions in human saliva by RT-QuIC SO PRION LA English DT Meeting Abstract C1 [Manca, Matteo; Caughey, Byron] NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT USA. [Zanusso, Gianluigi] Univ Verona, Dept Neurol & Movement Sci, I-37100 Verona, Italy. NR 0 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA P.13 BP S17 EP S17 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900031 ER PT J AU Moore, R Head, M Ironside, J Zanusso, G Choi, YP Priola, S AF Moore, Roger Head, Mark Ironside, James Zanusso, Gianluigi Choi, Young Pyo Priola, Suzette TI Variable relative contribution of methionine and valine at residue 129 to protease resistant prion protein in heterozygous cases of Creutzfeldt-Jakob disease SO PRION LA English DT Meeting Abstract C1 [Moore, Roger; Priola, Suzette] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Head, Mark; Ironside, James] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Zanusso, Gianluigi] Univ Verona, I-37100 Verona, Italy. [Choi, Young Pyo] Korea Brain Res Inst, Daegu, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA P.96 BP S61 EP S62 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900114 ER PT J AU Orru, CD Groveman, BR Raymond, LD Hughson, AG Nonno, R Zou, WQ Ghetti, B Gambetti, P Caughey, B AF Orru, Christina D. Groveman, Bradley R. Raymond, Lynne D. Hughson, Andrew G. Nonno, Romolo Zou, Wenquan Ghetti, Bernardino Gambetti, Pierluigi Caughey, Byron TI An apparently universal substrate for RT-QuIC-based detection and discrimination of prion strains SO PRION LA English DT Meeting Abstract C1 [Orru, Christina D.; Groveman, Bradley R.; Raymond, Lynne D.; Hughson, Andrew G.; Caughey, Byron] NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT USA. [Nonno, Romolo] Ist Super Sanita, Dept Vet Publ Hlth & Food Safety, I-00161 Rome, Italy. [Zou, Wenquan; Gambetti, Pierluigi] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. [Ghetti, Bernardino] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA P.47 BP S36 EP S36 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900065 ER PT J AU Race, B Phillips, K Meade-White, K Striebel, J Chesebro, B AF Race, Brent Phillips, Katie Meade-White, Kimberly Striebel, James Chesebro, Bruce TI Increased infectivity of anchorless mouse scrapie prions in transgenic mice overexpressing human prion protein SO PRION LA English DT Meeting Abstract C1 [Race, Brent; Phillips, Katie; Meade-White, Kimberly; Striebel, James; Chesebro, Bruce] NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR 24 PY 2015 VL 9 SU 1 MA P.94 BP S60 EP S61 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CI0RG UT WOS:000354444900112 ER EF