FN Thomson Reuters Web of Science™ VR 1.0 PT B AU Fischer, DJ Epstein, MS Epstein, JB AF Fischer, Dena J. Epstein, Matthew S. Epstein, Joel B. BE Patton, LL Glick, M TI Bleeding Disorders SO ADA PRACTICAL GUIDE TO PATIENTS WITH MEDICAL CONDITIONS, 2ND EDITION LA English DT Article; Book Chapter ID ORAL ANTICOAGULANTS; DENTAL EXTRACTION; PLATELET-FUNCTION; MANAGEMENT; THERAPY; WARFARIN; DISEASE; COAGULOPATHY; HEMOPHILIA; GUIDELINES C1 [Fischer, Dena J.] Natl Inst Dent & Craniofacial Res, Clin Res & Epidemiol Program, Bethesda, MD 20892 USA. RP Fischer, DJ (reprint author), Natl Inst Dent & Craniofacial Res, Clin Res & Epidemiol Program, Bethesda, MD 20892 USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA BN 978-1-118-92440-2; 978-1-118-92928-5 PY 2016 BP 183 EP 200 PG 18 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BF9MB UT WOS:000385752800010 ER PT J AU Carsamer, E AF Carsamer, Emmanuel TI Volatility transmission in African foreign exchange markets SO AFRICAN JOURNAL OF ECONOMIC AND MANAGEMENT STUDIES LA English DT Article DE Augmented dynamic conditional correlation; Financial integration; Volatility transmission ID CONDITIONAL CORRELATION; FINANCIAL CRISIS; STOCK MARKETS; GARCH MODEL; CONTAGION; TRADE; UNION; RATES; ARCH AB Purpose - The concept of volatility transmission and co-movement has witnessed a resurgence in the international finance literature in recent years after the black swan events which gave evidence of financial market linkages. The purpose of this paper is to examine the dynamic sources of volatility transmission in the foreign exchange market in recent financial market integration in Africa. Design/methodology/approach - A conceptual framework was adapted from the extant literature and was used as the basis of modeling exchange rate volatility transmission. This paper adopts a quantitative research approach and opts for augmented DCC model to empirically unearth the sources of exchange rate volatility transmission. Findings - The key findings of the study are that, the African market is more prone to shock from outside than in the region. Macroeconomic news surprises influence volatility transmission and co-movements. Robust support is found for trade balance, interest rate and gross domestic product. These findings clearly demonstrate the low level of financial development and challenges that sometimes exist in exchange rate-policy implementation by policy makers. Research limitations/implications - Interested academics and practitioners working in the area might incorporate bilateral investment into the model of exchange rate correlation in future research. Originality/value - Unilaterally considering exchange rate volatility transmission and subsequent augmentation of the DCC model, this study makes a modest contribution to the examination of exchange rate correlations in Africa. This study makes an important contribution in not only addressing this imbalance, but more importantly improving the relative literature on exchange rate volatility transmission. C1 [Carsamer, Emmanuel] NIDA, Sch Dev Econ, Bangkok, Thailand. [Carsamer, Emmanuel] Univ Educ, Dept Econ, Winneba, Ghana. RP Carsamer, E (reprint author), NIDA, Sch Dev Econ, Bangkok, Thailand.; Carsamer, E (reprint author), Univ Educ, Dept Econ, Winneba, Ghana. EM carsamere@yahoo.com NR 83 TC 0 Z9 0 U1 2 U2 2 PU EMERALD GROUP PUBLISHING LTD PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY BD16 1WA, W YORKSHIRE, ENGLAND SN 2040-0705 EI 2040-0713 J9 AFR J ECON MANAG STU JI Afr. J. Econ. Manag. Stud. PY 2016 VL 7 IS 2 BP 205 EP 224 DI 10.1108/AJEMS-05-2015-0056 PG 20 WC Economics SC Business & Economics GA ED6RY UT WOS:000388984800004 ER PT J AU Grammatikakis, I Zhang, PS Mattson, MP Gorospe, M AF Grammatikakis, Ioannis Zhang, Peisu Mattson, Mark P. Gorospe, Myriam TI The long and the short of TRF2 in neurogenesis SO CELL CYCLE LA English DT Article DE Neuronal development; RNA-binding proteins; splicing; ribonucleoprotein complex; REST; HNRNPH ID CHROMOSOME-END PROTECTION; HUMAN TELOMERIC PROTEINS; REPEAT-CONTAINING RNA; MAMMALIAN TELOMERES; DAMAGE RESPONSE; STEM-CELLS; DNA; BINDING; LOOP; PLASTICITY AB Gene expression patterns change dramatically during neuronal development. Proliferating cells, including neural stem cells (NSCs), express telomere repeat-binding factor 2 (TRF2), a nuclear protein that associates with telomeric proteins, DNA, and RNA telomeres. In NSCs TRF2 also binds to the transcription regulator REST to facilitate repression of numerous neuron-specific genes, thereby keeping the NSCs in a self-renewing state. Upon neuronal differentiation, TRF2 levels decline, REST-regulated neuronal genes are derepressed, and a short isoform of TRF2 arises (TRF2-S) which localizes in the cytoplasm, associates with different subsets of proteins and transcripts, and mobilizes axonal G-rich mRNAs. We recently identified two RNA-binding proteins, HNRNPH1 and H2 (referred to jointly as HNRNPH due to their high homology), which mediate the alternative splicing of an exon required for the expression of full-length TRF2. As HNRNPH levels decline during neurogenesis, TRF2 abundance decreases and TRF2-S accumulates. Here, we discuss the shared and unique functions of TRF2 and TRF2-S, the distinct subcellular compartment in which each isoform resides, the subsets of proteins and nucleic acids with which each interacts, and the functional consequences of these ribonucleoprotein interactions. This paradigm illustrates the dynamic mechanisms through which splicing regulation by factors like HNRNPH enable distinct protein functions as cells adapt to developmental programs such as neurogenesis. C1 [Grammatikakis, Ioannis; Gorospe, Myriam] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Zhang, Peisu; Mattson, Mark P.] NIA, Lab Neurosci, NIH, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, Genet Lab, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov FU NIA-IRP, NIH [Z01-AG000518-11] FX This work was funded in its entirety by the NIA-IRP, NIH, project Z01-AG000518-11. NR 64 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 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2016 VL 15 IS 22 BP 3026 EP 3032 DI 10.1080/15384101.2016.1222339 PG 7 WC Cell Biology SC Cell Biology GA EC8EX UT WOS:000388374500017 PM 27565210 ER PT B AU Jacobs, L Remington, JS Melton, ML AF Jacobs, Leon Remington, Jack S. Melton, Marjorie L. BE Janovy, J Esch, GW TI A SURVEY OF MEAT SAMPLES FROM SWINE, CATTLE, AND SHEEP FOR THE PRESENCE OF ENCYSTED TOXOPLASMA SO CENTURY OF PARASITOLOGY: DISCOVERIES, IDEAS AND LESSONS LEARNED BY SCIENTISTS WHO PUBLISHED IN THE JOURNAL OF PARASITOLOGY, 1914-2014 LA English DT Reprint; Book Chapter C1 [Jacobs, Leon; Remington, Jack S.; Melton, Marjorie L.] NIAID, US Dept Hlth Educ & Welf, Publ Hlth Serv, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Jacobs, L (reprint author), NIAID, US Dept Hlth Educ & Welf, Publ Hlth Serv, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-88478-2; 978-1-118-88476-8 PY 2016 D2 10.1002/9781118884799 PG 6 WC History & Philosophy Of Science; Parasitology SC History & Philosophy of Science; Parasitology GA BF8CT UT WOS:000384715000019 ER PT B AU Knight, AL Chen, YM Sun, T Sheng, ZH AF Knight, Adam L. Chen, Yanmin Sun, Tao Sheng, Zu-Hang BE Gribkoff, VK Jonas, EA Hardwick, JM TI NEURONAL MITOCHONDRIAL TRANSPORT SO FUNCTIONS, DISEASE-RELATED DYSFUNCTIONS, AND THERAPEUTIC TARGETING OF NEURONAL MITOCHONDRIA SE Wiley Series on Neuropharmacology LA English DT Article; Book Chapter ID FAST AXONAL-TRANSPORT; KINESIN HEAVY-CHAIN; NERVE GROWTH-FACTOR; SYNAPTIC-TRANSMISSION; CYTOPLASMIC DYNEIN; IN-VIVO; NEURODEGENERATIVE DISEASES; SYMPATHETIC NEURONS; CORTICAL-NEURONS; BINDING DOMAIN C1 [Knight, Adam L.; Chen, Yanmin; Sun, Tao; Sheng, Zu-Hang] NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Knight, AL (reprint author), NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 104 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA BN 978-1-119-01672-4; 978-1-118-70923-8 J9 WILEY SER NEUROPH PY 2016 BP 166 EP 185 PG 20 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA BF9SQ UT WOS:000385861800008 ER PT J AU Yoneda, M Xu, L Kajiyama, H Kawabe, S Paiz, J Ward, JM Kimura, S AF Yoneda, Mitsuhiro Xu, Lei Kajiyama, Hiroaki Kawabe, Shuko Paiz, Jorge Ward, Jerrold M. Kimura, Shioko TI Secretoglobin Superfamily Protein SCGB3A2 Alleviates House Dust Mite-Induced Allergic Airway Inflammation in Mice SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE SCGB3A2; Lung-enriched cytokine like protein; Anti-inflammation; Antifibrosis; Growth factor; House dust mite; Allergic airway inflammation; Mouse model ID INDUCED PULMONARY-FIBROSIS; STEM-CELL FACTOR; LUNG DEVELOPMENT; ASTHMA; EXPRESSION; GENE; 3A2; UTEROGLOBIN; RECEPTOR; DISEASE AB Background: Secretoglobin (SCGB) 3A2, a novel, lung-enriched, cytokine-like, secreted protein of small molecular weight, was demonstrated to exhibit various biological functions including anti-inflammatory, antifibrotic and growthfactor activities. Anti-inflammatory activity was uncovered using the ovalbumin-induced allergic airway inflammation model. However, further validation of this activity using knockout mice in a different allergic inflammation model is necessary in order to establish the antiallergic inflammatory role for this protein. Methods: Scgb3a2-null (Scgb3a2(-/-)) mice were subjected to nasal inhalation of Dermatophagoides pteronyssinus extract for 5 days/week for 5 consecutive weeks; control mice received nasal inhalation of saline as a comparator. Airway inflammation was assessed by histological analysis, the number of inflammatory cells and various Th2-type cytokine levels in the lungs and bronchoalveolar lavage fluids by qRT-PCR and ELISA, respectively. Results: Exacerbated inflammation was found in the airway of Scgb3a2(-/-) mice subjected to house dust mite (HDM)-induced allergic airway inflammation compared with saline-treated control groups. All the inflammation end points were increased in the Scgb3a2(-/-) mice. The Ccr4 and Ccl17 mRNA levels were higher in HDM-treated lungs of S cgb3a2(-/-) mice than wild-type mice or saline-treated S cgb3a2(-/-) mice, whereas no changes were observed for Ccr3 and Ccl11 mRNA levels. Conclusions: These results demonstrate that SCGB3A2 has an anti-inflammatory activity in the HDM-induced allergic airway inflammation model, in which SCGB3A2 may modulate the CCR4-CCL17 pathway. SCGB3A2 may provide a useful tool to treat allergic airway inflammation, and further studies on the levels and function of SCGB3A2 in asthmatic patients are warranted. (C) 2016 S. Karger AG, Basel C1 [Yoneda, Mitsuhiro; Xu, Lei; Kajiyama, Hiroaki; Kawabe, Shuko; Paiz, Jorge; Kimura, Shioko] NCI, Lab Metab, NIH, 9000 Rockville Pike,Bldg 37,Rm 3106, Bethesda, MD 20892 USA. [Ward, Jerrold M.] Global VetPathol, Montgomery Village, MD USA. [Kajiyama, Hiroaki] Nagoya Univ, Grad Sch Med, Dept Obstet & Gynecol, Nagoya, Aichi, Japan. RP Kimura, S (reprint author), NCI, Lab Metab, NIH, 9000 Rockville Pike,Bldg 37,Rm 3106, Bethesda, MD 20892 USA. EM kimuras@mail.nih.gov FU Intramural Research Program of the National Cancer Institute [ZIABC010449] FX We would like to thank Drs. Stewart Levine and Xianglan Yao (National Heart, Lung and Blood Institute, Bethesda, Md., USA) for their advice and help on experiments using the HDM-induced allergic inflammation model and ex vivo cultures of MLN cells. This work was supported by the Intramural Research Program of the National Cancer Institute (ZIABC010449). NR 31 TC 0 Z9 0 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 EI 1423-0097 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 2016 VL 171 IS 1 BP 36 EP 44 DI 10.1159/000450788 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA EC9EG UT WOS:000388446500003 PM 27820933 ER PT J AU Fan, J Song, JB Liu, YJ Yu, GC Ma, Y Deng, Y He, NG Zhang, FW AF Fan, Jing Song, Jibin Liu, Yijing Yu, Guocan Ma, Ying Deng, Yan He, Nongyue Zhang, Fuwu TI Synthesis of biocompatible polymeric nanomaterial dually loaded with paclitaxel and nitric oxide for anti-MDR cancer therapy SO RSC ADVANCES LA English DT Article ID IN-VIVO; MULTIDRUG-RESISTANCE; RELEASE; CELLS; NANOPARTICLES; DOXORUBICIN; CHEMOSENSITIZATION; NANOMEDICINE; EFFICACY; DELIVERY AB Nitric oxide (NO) as a chemosensitizer has attracted a lot of attention in anti-multidrug resistance (MDR) tumor therapy. In this study, a three-segment amphiphilic copolymer was synthesized through click reaction by azido and alkyne groups. The PEI part with abundant secondary amines was utilized to load NO gas molecules, the hydrophobic PLLA core to encapsulate the hydrophobic drug paclitaxel (PTX), and the mPEG shell to provide a hydrophilic interface and lead the copolymer to self-assemble into micelles in the water phase for biological applications. This multifunctional mPEG-PEI-PLLA-PTX-NO nanostructure is able to release NO spontaneously under physiological conditions and enhance the cytotoxicity for synergistic treatment of PTX and NO, demonstrating the potential to treat MDR tumors. C1 [Fan, Jing; Deng, Yan; He, Nongyue] Southeast Univ, State Key Lab Bioelect, Nanjing 210096, Jiangsu, Peoples R China. [Fan, Jing; Song, Jibin; Liu, Yijing; Yu, Guocan; Ma, Ying; Zhang, Fuwu] Natl Inst Biomed Imaging & Bioengin, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP He, NG (reprint author), Southeast Univ, State Key Lab Bioelect, Nanjing 210096, Jiangsu, Peoples R China.; Zhang, FW (reprint author), Natl Inst Biomed Imaging & Bioengin, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM nyhe1958@163.com; fuwu.zhang@nih.gov FU Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health; National Key Program for Developing Basic Research of China [2014CB744501]; NSFC [61271056, 61471168, 61527806]; State Scholarship Fund from China Scholarship Council [201406090085] FX We thank the financial support from the Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, the National Key Program for Developing Basic Research of China (2014CB744501), the NSFC (61271056, 61471168, and 61527806), and the State Scholarship Fund from China Scholarship Council (201406090085). NR 34 TC 0 Z9 0 U1 2 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2046-2069 J9 RSC ADV JI RSC Adv. PY 2016 VL 6 IS 107 BP 105871 EP 105877 DI 10.1039/c6ra23637e PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA EC4PW UT WOS:000388116500108 ER PT S AU Weinrich, M AF Weinrich, Michael BE Cullum, BM Kiehl, D McLamore, ES TI Special Challenges and Opportunities for Application of Bio-Medical Sensors SO SMART BIOMEDICAL AND PHYSIOLOGICAL SENSOR TECHNOLOGY XIII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Smart Biomedical and Physiological Sensor Technology XIII CY APR 18-19, 2016 CL Baltimore, MD SP SPIE ID IMPLANTS; DRUGS AB Real-time data from sensors can potentially transform the practice of medicine. This article compares progress in genetics with sensors to draw some lessons for investigators developing sensor technologies. Special opportunities for research funding related to sensors at the NIH and challenges for sensor applications are highlighted. C1 [Weinrich, Michael] NIH, Eunice Kennedy Shriver Inst Child Hlth & Human De, Bethesda, MD 20892 USA. RP Weinrich, M (reprint author), NIH, Eunice Kennedy Shriver Inst Child Hlth & Human De, Bethesda, MD 20892 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0104-8 J9 PROC SPIE PY 2016 VL 9863 AR UNSP 98630O DI 10.1117/12.2221907 PG 6 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Optics SC Engineering; Optics GA BG2WU UT WOS:000387732700017 ER PT J AU Tong, X Wang, ZT Sun, XL Song, JB Jacobson, O Niu, G Kiesewetter, DO Chen, XY AF Tong, Xiao Wang, Zhantong Sun, Xiaolian Song, Jibin Jacobson, Orit Niu, Gang Kiesewetter, Dale O. Chen, Xiaoyuan TI Size Dependent Kinetics of Gold Nanorods in EPR Mediated Tumor Delivery SO THERANOSTICS LA English DT Article DE gold nanorods; enhanced permeation and retention (EPR) effect; positron emission tomography (PET); kinetic modeling ID POSITRON-EMISSION-TOMOGRAPHY; PLASMONIC PHOTOTHERMAL THERAPY; DRUG-DELIVERY; CANCER-THERAPY; NANOPARTICLE SIZE; PARTICLE-SIZE; IN-VIVO; SHAPE; DESIGN; BIODISTRIBUTION AB Gold nanorods (AuNR) have been intensively used in nanomedicine for cancer diagnostics and therapy, due to their excellent plasmonic photothermal properties. Tuning the size and aspect ratio of AuNR tailors the localized surface plasmon resonance (LSPR) in the NIR spectrum at which biological tissues are transparent, thus enables specific and effective treatment. The AuNR extravasates into tumor interstitium through enhanced permeation and retention (EPR) effect. Efficient AuNR based cancer therapy requires efficient AuNR tumor delivery. However, the size of AuNR can dramatically affect its blood circulation and tumor accumulation. Here we proposed for the first time a systematic framework to investigate the size-dependent kinetics of AuNRs during EPR mediated tumor delivery. By using Cu-64-labeled AuNRs with positron emission tomography (PET) and kinetic modeling, the in vivo uptake and kinetics of Cu-64-AuNR during its blood circulation, tumor accumulation and elimination were studied both in vitro and in vivo. The results of different sized AuNRs were compared and the optimum size of AuNR was suggested for EPR mediated tumor delivery. Our study provides a better understanding of the in vivo behavior of AuNR, which can help future design of nanomaterials for cancer imaging and therapy. C1 [Tong, Xiao; Wang, Zhantong; Sun, Xiaolian; Song, Jibin; Jacobson, Orit; Niu, Gang; Kiesewetter, Dale O.; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov NR 46 TC 0 Z9 0 U1 18 U2 18 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2016 VL 6 IS 12 BP 2039 EP 2051 DI 10.7150/thno.17098 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ED0AR UT WOS:000388505900003 PM 27698939 ER PT S AU Belyantseva, IA AF Belyantseva, Inna A. BE Sokolowski, B TI Helios (R) Gene Gun-Mediated Transfection of the Inner Ear Sensory Epithelium: Recent Updates SO AUDITORY AND VESTIBULAR RESEARCH: METHODS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Biolistic transfection; Gene gun; Inner ear; Hair cell; Stereocilia; Myosin; Whirlin; Actin; Clic5; Immunofluorescence; GFP ID HAIR-CELL STEREOCILIA; HIGH-VELOCITY MICROPROJECTILES; IN-VIVO ELECTROPORATION; GUINEA-PIG COCHLEA; BIOLISTIC TRANSFECTION; MYOSIN-XVA; MOLECULAR TREADMILL; FOREIGN GENES; PROTEIN; MOUSE AB The transfection of vertebrate inner ear hair cells has proven to be challenging. Therefore, many laboratories attempt to use and improve different transfection methods. Each method has its own advantages and disadvantages. A particular researcher's skills in addition to available equipment and the type of experiment (in vivo or in vitro) likely determine the transfection method of choice. Biolistic delivery of exogenous DNA, mRNA, or siRNA, also known as Helios Gene Gun-mediated transfection, uses the mechanical energy of compressed helium gas to bombard tissue with micron- or submicron-sized DNA or RNA coated gold particles, which can penetrate and transfect cells in vitro or in vivo. Helios Gene Gun mediated transfection has several advantages: (1) it is simple enough to learn in a short time; (2) it is designed to overcome cell barriers even as tough as plant cell membrane or stratum corneum in the epidermis; (3) it can transfect cells deep inside a tissue such as specific neurons within a brain slice; (4) it can accommodate mRNA, siRNA, or DNA practically of any size to be delivered; and (5) it works well with various cell types including non-dividing, terminally differentiated cells that are difficult to transfect, such as neurons or mammalian inner ear sensory hair cells. The latter advantage is particularly important for inner ear research. The disadvantages of this method are: (1) low efficiency of transfection due to many variables that have to be adjusted and (2) potential mechanical damage of the tissue if the biolistic shot parameters are not optimal. This chapter provides a step-by-step protocol and critical evaluation of the Bio-Rad Helios Gene Gun transfection method used to deliver green fluorescent protein (GFP)-tagged full-length cDNAs of myosin 15a, whirlin, (3-actin, and ClicS into rodent hair cells of the postnatal inner ear sensory epithelia in culture. C1 [Belyantseva, Inna A.] Natl Inst Deafness & Other Commun, Mol Genet Lab, Sect Human Genet, NIH, Bethesda, MD 20892 USA. RP Belyantseva, IA (reprint author), Natl Inst Deafness & Other Commun, Mol Genet Lab, Sect Human Genet, NIH, Bethesda, MD 20892 USA. NR 64 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1064-3745 BN 978-1-4939-3615-1; 978-1-4939-3613-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1427 BP 3 EP 26 DI 10.1007/978-1-4939-3615-1_1 D2 10.1007/978-1-4939-3615-1 PG 24 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG1HW UT WOS:000386789500002 PM 27259918 ER PT S AU Yaniv, Z AF Yaniv, Ziv BE Zheng, G Li, S TI Registration for Orthopaedic Interventions SO COMPUTATIONAL RADIOLOGY FOR ORTHOPAEDIC INTERVENTIONS SE Lecture Notes in Computational Vision and Biomechanics LA English DT Article; Book Chapter ID CONE-BEAM CT; TOTAL HIP-ARTHROPLASTY; DISTAL RADIUS OSTEOTOMY; X-RAY IMAGES; COMPUTER-ASSISTED SURGERY; STATISTICAL SHAPE MODELS; PEDICLE SCREW PLACEMENT; TO-WORLD REGISTRATION; GUIDED SPINE SURGERY; LUMBAR SPINE AB Registration is the process of computing the transformation that relates the coordinates of corresponding points viewed in two different coordinate systems. It is one of the key components in orthopaedic navigation guidance and robotic systems. When assessing the appropriateness of a registration method for clinical use one must consider multiple factors. Among others these include, accuracy, robustness, speed, degree of automation, detrimental effects to the patient, effects on interventional workflow, and associated financial costs. In this chapter we give an overview of registration algorithms, both those available commercially and those that have only been evaluated in the laboratory setting. We introduce the models underlying the algorithms, describe the context in which they are used and assess them using the criteria described above. We show that academic research has primarily focused on improving all aspects of registration while ignoring workflow related issues. On the other hand, commercial systems have found ways of obviating the need for registration resulting in streamlined workflows that are clinically more acceptable, albeit at a cost of being sub-optimal on other criteria. While there is no optimal registration method for all settings, we do have a respectable arsenal from which to choose. C1 [Yaniv, Ziv] TAJ Technol Inc, Mendota Hts, MN 55120 USA. [Yaniv, Ziv] NIH, Off High Performance Comp & Commun, Natl Lib Med, Bethesda, MD 20894 USA. RP Yaniv, Z (reprint author), TAJ Technol Inc, Mendota Hts, MN 55120 USA. EM zivyaniv@nih.gov NR 154 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2212-9391 BN 978-3-319-23482-3; 978-3-319-23481-6 J9 L N COMPUT VIS BIOME PY 2016 BP 41 EP 70 DI 10.1007/978-3-319-23482-3_3 D2 10.1007/978-3-319-23482-3 PG 30 WC Computer Science, Artificial Intelligence; Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA BF8BN UT WOS:000384685800004 ER PT J AU Abbott, AB Knickelbein, JE Wiley, HE Chew, EY Wong, WT AF Abbott, Akshar B. Knickelbein, Jared E. Wiley, Henry E. Chew, Emily Y. Wong, Wai T. TI Ocular von Hippel-Lindau Disease - clinical characteristics and future directions SO EXPERT REVIEW OF OPHTHALMOLOGY LA English DT Review DE Anti-angiogenic therapy; von Hippel-Lindau disease; retina capillary hemangioblastoma; retina; tumors; genetic diseases; VHL ID RETINAL CAPILLARY HEMANGIOMA; ENDOTHELIAL GROWTH-FACTOR; GENOTYPE-PHENOTYPE CORRELATION; DEPENDENT PROBE AMPLIFICATION; RECEPTOR INHIBITOR SU5416; TUMOR-SUPPRESSOR GENE; PHOTODYNAMIC THERAPY; TRANSPUPILLARY THERMOTHERAPY; INTRAVITREAL BEVACIZUMAB; MOLECULAR PATHOLOGY AB Introduction: von Hippel-Lindau (VHL) disease is an autosomal dominant, inherited multisystem cancer syndrome involving mutations in the VHL tumor suppressor gene. The hallmark lesion in ocular VHL disease is the retinal capillary hemangioblastoma (RCH), a benign vascular tumor capable of causing visual loss through exudative changes. Areas covered: Combining epidemiological and clinical data with an analysis of recent treatment and outcomes literature, this review aims to update the clinician on research findings and upcoming potential therapies. We describe the clinical features of ocular VHL disease and the factors that can help prognose visual outcome in affected patients and provide a summary of current treatment modalities. Expert commentary: We provide an update on the advent of genetic testing for pathogenic mutations in the VHL gene which has enabled earlier diagnoses and more detailed prognoses in affected patients, and have opened the way to future potential treatments aimed at the downstream molecular mediators of the disease. C1 [Abbott, Akshar B.; Knickelbein, Jared E.; Wiley, Henry E.; Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Wong, Wai T.] NEI, Unit Neuron Glia Interact, NIH, Bethesda, MD 20892 USA. RP Wong, WT (reprint author), NEI, Unit Neuron Glia Interact, NIH, Bethesda, MD 20892 USA. EM wongw@nei.nih.gov OI Wong, Wai/0000-0003-0681-4016 NR 103 TC 0 Z9 0 U1 2 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1746-9899 EI 1746-9902 J9 EXPERT REV OPHTHALMO JI Expert Rev. Ophthalmol. PY 2016 VL 11 IS 5 BP 329 EP 337 DI 10.1080/17469899.2016.1224652 PG 9 WC Ophthalmology SC Ophthalmology GA DW3TM UT WOS:000383565800003 ER PT J AU Henry, RK Gafni, RI AF Henry, Rohan K. Gafni, Rachel I. TI Hypercalcemia due to Milk-Alkali Syndrome and Fracture-Induced Immobilization in an Adolescent Boy with Hypoparathyroidism SO HORMONE RESEARCH IN PAEDIATRICS LA English DT Article DE Parathyroid hormone; Fracture; Bone formation; Hypercalcemia; Immobilization ID CALCIUM HOMEOSTASIS; BONE; OSTEOPOROSIS; CHILDREN; PATIENT; MICE AB Background: Hypercalcemia of immobilization, while rare, may occur in adolescent boys after fracture. Although not fully understood, the mechanism appears to be related to bone turnover uncoupling, in part mediated by upregulation of RANKL. Animal studies suggest that parathyroidectomy suppresses RANKL-stimulated osteoclastogenesis in immobilized bone. Thus, immobilization-induced hypercalcemia should be uncommon in patients with hypoparathy-roidism. Methods/Results: We present a 15-year-old boy with well-controlled hypoparathyroidism who developed hypercalcemia and milk-alkali syndrome 5 weeks after sustaining a severe tibia/fibula fracture requiring bedrest. Milkalkali syndrome (hypercalcemia, alkalosis, and renal insufficiency) results from chronic excessive ingestion of calcium and absorbable alkali. Prior to fracture, our patient had not experienced hypercalcemia despite high doses of supplements, necessary during puberty. Supplements were discontinued and his biochemistries normalized with saline diuresis and a dose of pamidronate. Alkaline phosphatase, which was low at presentation, returned to normal 5 weeks later with remobilization. Conclusions: Fracture and immobilization caused acute suppression of bone formation with persistent bone resorption in this rapidly growing adolescent; continuation of carbonate-containing calcium supplements resulted in the milk-alkali syndrome. Therefore, close monitoring of serum calcium with adjustments in supplementation are indicated in immobilized patients with hypoparathyroidism. (C) 2016 S. Karger AG, Basel C1 [Henry, Rohan K.] Nationwide Childrens Hosp, Sect Endocrinol Metab & Diabet, Columbus, OH USA. [Gafni, Rachel I.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Henry, RK (reprint author), Nationwide Childrens Hosp, 555 South 18th St, Columbus, OH 43205 USA. EM rohan.henry@nationwidechildrens.org FU Intramural Research Program of the NIH, NIDCR FX Work by R.I. Gafni is supported by the Intramural Research Program of the NIH, NIDCR. NR 23 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1663-2818 EI 1663-2826 J9 HORM RES PAEDIAT JI Horm. Res. Paediatr. PY 2016 VL 86 IS 3 BP 201 EP 205 DI 10.1159/000446316 PG 5 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA EC2SD UT WOS:000387973300008 PM 27184240 ER PT S AU Morris, SE Vaidyanathan, U Cuthbert, BN AF Morris, Sarah E. Vaidyanathan, Uma Cuthbert, Bruce N. BE Li, M Spaulding, WD TI Changing the Diagnostic Concept of Schizophrenia: The NIMH Research Domain Criteria Initiative SO NEUROPSYCHOPATHOLOGY OF SCHIZOPHRENIA: MOLECULES, BRAIN SYSTEMS, MOTIVATION, AND COGNITION SE Nebraska Symposium on Motivation LA English DT Article; Proceedings Paper CT 63rd Annual Nebraska Symposium on Motivation CY APR 09-10, 2015 CL Lincoln, NE ID AUDITORY VERBAL HALLUCINATIONS; PLURIPOTENT STEM-CELLS; OBSESSIVE-COMPULSIVE DISORDER; AUTOIMMUNE-DISEASES; GENERAL-POPULATION; PSYCHOTIC EXPERIENCES; CHILDHOOD TRAUMA; BIPOLAR DISORDER; PERSONALITY-DISORDER; PERINEURONAL NETS C1 [Morris, Sarah E.; Vaidyanathan, Uma; Cuthbert, Bruce N.] NIMH, Res Domain Criteria Unit, 6001 Execut Blvd, North Bethesda, MD 20892 USA. RP Morris, SE (reprint author), NIMH, Res Domain Criteria Unit, 6001 Execut Blvd, North Bethesda, MD 20892 USA. EM sarah.morris@nih.gov NR 119 TC 0 Z9 0 U1 8 U2 8 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0146-7875 BN 978-3-319-30596-7; 978-3-319-30594-3 J9 NEBR SYM MOTIV JI Nebr. Symp. Motiv. PY 2016 VL 63 BP 225 EP 252 DI 10.1007/978-3-319-30596-7_8 PG 28 WC Psychology, Biological; Neurosciences; Psychiatry; Psychology; Psychology, Experimental; Psychology, Social SC Psychology; Neurosciences & Neurology; Psychiatry GA BG3JW UT WOS:000387957600008 PM 27627829 ER PT B AU Hallett, M AF Hallett, Mark BE Kirton, A Gilbert, DL TI PEDIATRIC BRAIN STIMULATION MAPPING AND MODULATING THE DEVELOPING BRAIN Foreword SO PEDIATRIC BRAIN STIMULATION: MAPPING AND MODULATING THE DEVELOPING BRAIN LA English DT Editorial Material; Book Chapter C1 [Hallett, Mark] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS PI CLUJ-NAPOCA PA 3-5 MANASTUR STREET, CLUJ-NAPOCA, 400372, ROMANIA BN 978-0-12-802038-8; 978-0-12-802001-2 PY 2016 BP XV EP XVI PG 2 WC Neurosciences; Pediatrics SC Neurosciences & Neurology; Pediatrics GA BF8LB UT WOS:000385155500001 ER PT B AU Marsh, JCW Kulasekararaj, AG Young, NS Hillmen, P AF Marsh, Judith C. W. Kulasekararaj, Austin G. Young, Neal S. Hillmen, Peter BE Hoffbrand, AV Higgs, DR Keeling, DM Mehta, AB TI Acquired aplastic anaemia and paroxysmal nocturnal haemoglobinuria SO POSTGRADUATE HAEMATOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID CLONAL HEMATOPOIESIS; SOMATIC MUTATIONS C1 [Marsh, Judith C. W.] Kings Coll Hosp London, Kings Coll London, London, England. [Kulasekararaj, Austin G.] Kings Coll Hosp London, Kings Coll London, Dept Haematol, London, England. [Hillmen, Peter] St James Univ Hosp, Leeds, W Yorkshire, England. [Young, Neal S.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Marsh, JCW (reprint author), Kings Coll Hosp London, Kings Coll London, London, England. NR 11 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-85447-1; 978-1-118-85432-7 PY 2016 BP 174 EP 194 PG 21 WC Hematology SC Hematology GA BF8CS UT WOS:000384714400011 ER PT S AU Newman, DJ Cragg, GM AF Newman, David J. Cragg, Gordon M. BE Brase, S TI Natural Product Scaffolds of Value in Medicinal Chemistry SO PRIVILEGED SCAFFOLDS IN MEDICINAL CHEMISTRY: DESIGN, SYNTHESIS, EVALUATION SE RSC Drug Discovery Series LA English DT Article; Book Chapter ID VINCA-ROSEA-LINN; RAPAMYCIN AY-22,989; DRUG DISCOVERY; BIOLOGICAL-ACTIVITY; STREPTOMYCES-HYGROSCOPICUS; TRASTUZUMAB EMTANSINE; GELDANAMYCIN ANALOGS; LAMELLARIN ALKALOIDS; ESCHERICHIA-COLI; CHEMICAL SPACE C1 [Newman, David J.; Cragg, Gordon M.] NCI, Nat Prod Branch, Dev Therapeut Program, DCTD,Frederick Natl Lab, POB B, Frederick, MD 21702 USA. RP Newman, DJ (reprint author), NCI, Nat Prod Branch, Dev Therapeut Program, DCTD,Frederick Natl Lab, POB B, Frederick, MD 21702 USA. EM dn22a@nih.gov NR 121 TC 0 Z9 0 U1 2 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 2041-3203 BN 978-1-78262-224-6 J9 RSC DRUG DISCOV JI RSC Drug Discov. PY 2016 VL 50 BP 348 EP 378 PG 31 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BG3NQ UT WOS:000388088400014 ER PT B AU Murphy, ER Broach, WH Kouse, AB AF Murphy, Erin R. Broach, William H. Kouse, Andrew B. BE Picking, WD Picking, WL TI Ribo-regulation in Shigella SO SHIGELLA: MOLECULAR AND CELLULAR BIOLOGY LA English DT Article; Book Chapter ID ACTIN-BASED MOTILITY; HEME IRON-TRANSPORT; VIRULENCE GENE ICSA; ESCHERICHIA-COLI; SMALL RNA; MESSENGER-RNA; ANTISENSE RNA; TRANSCRIPTIONAL LEVEL; COMPARATIVE GENOMICS; PATHOGENIC BACTERIA AB Bacterial ribo-regulators are a diverse collection of molecules defined here as any RNA molecule that functions to specifically control the expression of a target gene(s), or the activity of a target protein. While the role of regulatory proteins in controlling virulence gene expression in Shigella species has long been appreciated, the role of RNA mediated regulation on this process is just now coming into focus. Recent advances have revealed that ribo-regulators play a central role in modulating Shigella gene expression in response to changes in specific environmental conditions, a process that is essential to the survival and virulence of these important pathogens. This chapter will present a general overview of bacterial ribo-regulators, followed by a detailed discussion of each Shigella ribo-regulator characterized to date. Special emphasis will be placed on the role that each known Shigella ribo-regulator plays in facilitating the survival and/or virulence of these significant pathogens. C1 [Murphy, Erin R.] Ohio Univ, Heritage Coll Osteopath Med, Dept Biomed Sci, Athens, OH 45701 USA. [Broach, William H.] Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL USA. [Kouse, Andrew B.] NIH, Cell Biol & Metab Program, Eunice Kennedy Shriver, Bldg 10, Bethesda, MD 20892 USA. RP Murphy, ER (reprint author), Ohio Univ, Heritage Coll Osteopath Med, Dept Biomed Sci, Athens, OH 45701 USA. EM murphye@ohio.edu NR 121 TC 0 Z9 0 U1 0 U2 0 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-910190-19-7 PY 2016 BP 109 EP 137 PG 29 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA BG3AY UT WOS:000387832800005 ER PT J AU Planchart, A Mattingly, CJ Allen, D Ceger, P Casey, W Hinton, D Kanungo, J Kullman, SW Tal, T Bondesson, M Burgess, SM Sullivan, C Kim, C Behl, M Padilla, S Reif, DM Tanguay, RL Hamm, J AF Planchart, Antonio Mattingly, Carolyn J. Allen, David Ceger, Patricia Casey, Warren Hinton, David Kanungo, Jyotshna Kullman, Seth W. Tal, Tamara Bondesson, Maria Burgess, Shawn M. Sullivan, Con Kim, Carol Behl, Mamta Padilla, Stephanie Reif, David M. Tanguay, Robert L. Hamm, Jon TI Advancing Toxicology Research Using In Vivo High Throughput Toxicology with Small Fish Models SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Article DE aquatic models; 21st century toxicology; alternatives ID ZEBRAFISH DANIO-RERIO; TRANSMEMBRANE CONDUCTANCE REGULATOR; ENDOCRINE-DISRUPTING CHEMICALS; MATERNAL STILBESTROL THERAPY; ARYL-HYDROCARBON RECEPTOR; INNATE IMMUNE-RESPONSE; ZINC-FINGER NUCLEASES; CYPRINUS-CARPIO L.; ENVIRONMENTAL CHEMICALS; TRANSGENIC ZEBRAFISH AB Small freshwater fish models, especially zebrafish, offer advantages over traditional rodent models, including low maintenance and husbandry costs, high fecundity, genetic diversity, physiology similar to that of traditional biomedical models, and reduced animal welfare concerns. The Collaborative Workshop on Aquatic Models and 21st Century Toxicology was held at North Carolina State University on May 5-6, 2014, in Raleigh, North Carolina, USA. Participants discussed the ways in which small fish are being used as models to screen toxicants and understand mechanisms of toxicity. Workshop participants agreed that the lack of standardized protocols is an impediment to broader acceptance of these models, whereas development of standardized protocols, validation, and subsequent regulatory acceptance would facilitate greater usage. Given the advantages and increasing application of small fish models, there was widespread interest in follow-up workshops to review and discuss developments in their use. In this article, we summarize the recommendations formulated by workshop participants to enhance the utility of small fish species in toxicology studies, as well as many of the advances in the field of toxicology that resulted from using small fish species, including advances in developmental toxicology, cardiovascular toxicology, neurotoxicology, and immunotoxicology. We also review many emerging issues that will benefit from using small fish species, especially zebrafish, and new technologies that will enable using these organisms to yield results unprecedented in their information content to better understand how toxicants affect development and health. C1 [Planchart, Antonio; Mattingly, Carolyn J.; Kullman, Seth W.; Reif, David M.] North Carolina State Univ, Dept Biol Sci, Campus Box 7633, Raleigh, NC 27695 USA. [Planchart, Antonio; Mattingly, Carolyn J.; Kullman, Seth W.; Reif, David M.] North Carolina State Univ, Ctr Human Hlth & Environm, Raleigh, NC USA. [Allen, David; Ceger, Patricia; Hamm, Jon] Integrated Lab Syst Inc, Res Triangle Pk, NC USA. [Casey, Warren] NIEHS, Natl Toxicol Program, Interagency Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. [Hinton, David] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA. [Kanungo, Jyotshna] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Tal, Tamara; Padilla, Stephanie] US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA. [Bondesson, Maria] Univ Houston, Dept Pharmacol & Pharmaceut Sci, Houston, TX USA. [Burgess, Shawn M.] NHGRI, Bethesda, MD 20892 USA. [Sullivan, Con; Kim, Carol] Univ Maine, Dept Mol & Biomed Sci, Orono, ME USA. [Sullivan, Con; Kim, Carol] Univ Maine, Grad Sch Biomed Sci & Engn, Orono, ME USA. [Behl, Mamta] NIEHS, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. [Tanguay, Robert L.] Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. RP Planchart, A (reprint author), North Carolina State Univ, Dept Biol Sci, Campus Box 7633, Raleigh, NC 27695 USA. EM ajplanch@ncsu.edu OI Tal, Tamara/0000-0001-8365-9385 FU North Carolina State University Center for Human Health and the Environment (NIH/NIEHS) [P30ES025128] FX The authors would like to thank Ms. Catherine Sprankle of Integrated Laboratory Systems, Inc., for editorial assistance. Financial support for the workshop was provided by the North Carolina State University Center for Human Health and the Environment (NIH/NIEHS P30ES025128). NR 202 TC 1 Z9 1 U1 9 U2 9 PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH PI HEILDEBERG PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY SN 1868-596X EI 1868-8551 J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2016 VL 33 IS 4 BP 435 EP 452 DI 10.14573/altex.1601281 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EB5RY UT WOS:000387439200007 PM 27328013 ER PT J AU Song, HJ Rosano, JM Wang, Y Garson, CJ Prabhakarpandian, B Pant, K Klarmann, GJ Perantoni, A Alvarez, LM Lai, E AF Song, Hongjun Rosano, Jenna M. Wang, Yi Garson, Charles J. Prabhakarpandian, Balabhaskar Pant, Kapil Klarmann, George J. Perantoni, Alan Alvarez, Luis M. Lai, Eva TI Identification of mesenchymal stem cell differentiation state using dual-micropore microfluidic impedance flow cytometry SO ANALYTICAL METHODS LA English DT Article ID BONE-MARROW; BLOOD; PARTICLES; COUNTER; REPAIR; TISSUE; SENSOR AB As stem cell therapies become more common in the clinic, there is a greater need for real-time, label-free monitoring of the differentiation status of the cells. In this paper, we present a dual-micropore-based, high-throughput microfluidic electrical impedance flow cytometer for non-invasive identification of the differentiation state of mesenchymal stem cells. The mesenchymal stem cells were induced to differentiate into osteoblasts over a 21 day period. Samples of mesenchymal stem cells and osteoblasts were flowed through the device, and impedance measurements were acquired over a frequency range from 50 kHz to 10 MHz. The opacity and relative angle, which shed light on the membrane capacitance and interior dielectric properties of cells, were used as interrogation parameters to analyze collected impedance data. Specifically, identification of mesenchymal stem cells and osteoblasts in a mixed population was optimized using a combination of opacity signature at 500 kHz and relative angle at 3 MHz. Identification of both cell populations in a mixed sample was successfully achieved with an accuracy of 87%. The results show a progressive increase in the number of osteoblasts throughout the 21 day differentiation process, with 36% more mesenchymal stem cells differentiated after 14 days of induction compared to after just 7 days. The dual-micropore microfluidic impedance flow cytometer system may become an important non-invasive tool for assessing stem cell quality and differentiation stages for future regenerative medicine applications. C1 [Song, Hongjun; Rosano, Jenna M.; Wang, Yi; Garson, Charles J.; Prabhakarpandian, Balabhaskar; Pant, Kapil] CFD Res Corp, 701 McMillian Way NW, Huntsville, AL 35806 USA. [Klarmann, George J.; Perantoni, Alan; Alvarez, Luis M.] NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. [Alvarez, Luis M.] US Mil Acad, Dept Chem & Life Sci, West Point, NY 10996 USA. [Lai, Eva] Johns Hopkins Univ, Dept Chem & Biomol Engn, 3400 N Charles St, Baltimore, MD 21218 USA. [Lai, Eva] USAMRMC, 1054 Patchel St, Ft Detrick, MD 21702 USA. RP Wang, Y (reprint author), CFD Res Corp, 701 McMillian Way NW, Huntsville, AL 35806 USA. EM yi.wang@cfdrc.com FU U.S. Army Medical Research and Materiel Command (USAMRMC) [W81XWH-12-C-0069] FX This research was sponsored by the U.S. Army Medical Research and Materiel Command (USAMRMC) under contract W81XWH-12-C-0069. Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. GJK and LMA acknowledge Ms Nirmala Sharma of the Cancer and Developmental Biology Laboratory providing access to specialized tissue culture facilities and for discussions regarding analysis of differentiation and development markers. NR 30 TC 2 Z9 2 U1 9 U2 9 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1759-9660 EI 1759-9679 J9 ANAL METHODS-UK JI Anal. Methods PY 2016 VL 8 IS 41 BP 7437 EP 7444 DI 10.1039/c6ay01377e PG 8 WC Chemistry, Analytical; Food Science & Technology; Spectroscopy SC Chemistry; Food Science & Technology; Spectroscopy GA EB7WR UT WOS:000387602300001 ER PT S AU Gottesman, S AF Gottesman, Susan BE Gottesman, S TI Introduction SO ANNUAL REVIEW OF MICROBIOLOGY, VOL 70 SE Annual Review of Microbiology LA English DT Review; Book Chapter C1 [Gottesman, Susan] NCI, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4227 BN 978-0-8243-1170-4 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2016 VL 70 PG 1 WC Microbiology SC Microbiology GA BF6HF UT WOS:000383052200001 ER PT S AU Phillips, TM Wellner, E McMohan, S Kalish, H AF Phillips, Terry M. Wellner, Edward McMohan, Shane Kalish, Heather BE Tran, NT Taverna, M TI Measurement of Inflammatory Chemokines in Micro-dissected Tissue Biopsy Samples by Chip-Based Immunoaffinity Capillary Electrophoresis SO CAPILLARY ELECTROPHORESIS OF PROTEINS AND PEPTIDES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Capillary electrophoresis; Micro-dissection; Microchip; Immunoaffinity; Chemokines; Human biopsies ID HUMAN SKIN BIOPSIES; CYTOKINES; CE; MIGRATION; PATHOGENESIS; BIOMARKERS; ACTIVATION; PROFILES; DISEASE; MICE AB To aid in the biochemical analysis of human skin biopsies, a chip-based immunoaffinity capillary electrophoresis (ICE) system has been developed for measuring inflammatory chemokines in micro-dissected areas of the biopsy. Following isolation of the areas of interest, the tissue was solubilized and the analytes of interest were isolated by the immunoaffinity disk within the chip. The captured analytes were labeled in situ with a 635 nm light-emitting laser dye and electro-eluted into the chip separation channel. Electrophoretic separation of all of the analytes was achieved in 2.5 min with quantification of each peak being performed by online LIF detection and integration of each peak area. The degree of accuracy and precision achieved by the chip-based system is comparable to conventional immunoassays and the system is robust enough to be applied to the analysis of clinical samples. Further, with the expanding array of antibodies that are commercially available, this chip-based system can be applied to a wide variety of different biomedical and clinical analyses. C1 [Phillips, Terry M.; McMohan, Shane; Kalish, Heather] Natl Inst Biomed Imaging & Bioengn, Microanalyt Immunochem Unit, Biomed Engn & Phys Sci Shared Resource, NIH, Bethesda, MD USA. [Phillips, Terry M.] Natl Inst Biomed Imaging & Bioengn, Washington, DC USA. [Wellner, Edward] NIH, Bldg 10, Bethesda, MD 20892 USA. RP Phillips, TM (reprint author), Natl Inst Biomed Imaging & Bioengn, Microanalyt Immunochem Unit, Biomed Engn & Phys Sci Shared Resource, NIH, Bethesda, MD USA.; Phillips, TM (reprint author), Natl Inst Biomed Imaging & Bioengn, Washington, DC USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1064-3745 BN 978-1-4939-4014-1; 978-1-4939-4012-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1466 BP 121 EP 136 DI 10.1007/978-1-4939-4014-1_10 D2 10.1007/978-1-4939-4014-1 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG2RE UT WOS:000387585400011 PM 27473486 ER PT S AU Hereld, D Jin, T AF Hereld, Dale Jin, Tian BE Jin, T Hereld, D TI Chemotaxis Methods and Protocols preface SO CHEMOTAXIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Editorial Material; Book Chapter C1 [Hereld, Dale] NIAAA, NIH, Rockville, MD 20852 USA. [Jin, Tian] NIAID, Immunogenet Lab, Chemotaxis Signaling Sect, NIH, Rockville, MD 20852 USA. RP Hereld, D (reprint author), NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1064-3745 BN 978-1-4939-3480-5; 978-1-4939-3478-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1407 BP V EP V D2 10.1007/978-1-4939-3480-5 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG2YO UT WOS:000387780000001 ER PT S AU Meena, NP Kimmel, AR AF Meena, Netra Pal Kimmel, Alan R. BE Jin, T Hereld, D TI Biochemical Responses to Chemically Distinct Chemoattractants During the Growth and Development of Dictyostelium SO CHEMOTAXIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE cAMP; Folate; GPCR; ERK; mTORC2; Deamination; Methotrexate ID CHEMOTAXIS; DISCOIDEUM; ACTIVATION; MECHANISMS; PATHWAY AB Dictyostelium discoideum has proven an excellent model for the study of eukaryotic chemotaxis. During growth in its native environment, Dictyostelium phagocytose bacteria and fungi for primary nutrient capture. Growing Dictyostelium can detect these nutrient sources through chemotaxis toward the metabolic by-product folate. Although Dictyostelium grow as individual cells, nutrient depletion induces a multicellular development program and a separate chemotactic response pathway. During development, Dictyostelium synthesize and secrete cAMP, which serves as a chemoattractant to mobilize and coordinate cells for multicellular formation and development. Separate classes of GPCRs and Ga proteins mediate chemotactic signaling to the chemically distinct ligands. We discuss common and separate component responses of Dictyostelium to folate and cAMP during growth and development, and the advantages and disadvantages for each. As examples, we present biochemical assays to characterize the chemoattractantinduced kinase activations of mTORC2 and the ERKs. C1 [Meena, Netra Pal; Kimmel, Alan R.] NIDDKD, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Meena, NP (reprint author), NIDDKD, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1064-3745 BN 978-1-4939-3480-5; 978-1-4939-3478-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1407 BP 141 EP 151 DI 10.1007/978-1-4939-3480-5_11 D2 10.1007/978-1-4939-3480-5 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG2YO UT WOS:000387780000012 PM 27271900 ER PT S AU Park, C Hwang, IY Kehrl, JH AF Park, Chung Hwang, Il-Young Kehrl, John H. BE Jin, T Hereld, D TI Intravital Two-Photon Imaging of Lymphocytes Crossing High Endothelial Venules and Cortical Lymphatics in the Inguinal Lymph Node SO CHEMOTAXIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE High endothelial venules (HEVs); Cortical lymphatics; Lymphocytes; Inguinal lymph node (LN); Intravital imaging; Two-photon microscopy ID CELL-INTERACTIONS; B-LYMPHOCYTES; IN-VIVO; RECEPTOR; TRAFFICKING; MIGRATION; EGRESS; MICROSCOPY; MOTILITY; ORGANS AB Lymphocyte recirculation through lymph nodes (LNs) requires their crossing of endothelial barriers present in blood vessels and lymphatics by means of chemoattractant-triggered cell migration. The chemoattractant-chemoattractant receptor axes that predominately govern the traffi cking of lymphocytes into, and out of, LNs are CCL19/CCR7 and sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1PR1), respectively. Blood-borne lymphocytes downregulate S1PR1 and use CCR7 signaling to adhere to high endothelial venules (HEVs) for transmigration. During their LN residency, recirculating lymphocytes reacquire S1PR1 and attenuate their sensitivity to chemokines. Eventually lymphocytes exit the LN by entering the cortical or medullary lymphatics, a process that depends upon S1PR1 signaling. Upon entering into the lymph, lymphocytes lose their polarity, downregulate their sensitivity to S1P due to the high concentration of S1P, and upregulate their sensitivity to chemokines. However, many of the details of lymphocyte transmigration across endothelial barriers remain poorly understood. Intravital two-photon imaging with advanced microscope technologies not only allows the real-time observation of immune cells in intact LN of a live mouse, but also provides a means to monitor the interactions between circulating lymphocytes and stromal barriers. Here, we describe procedures to visualize lymphocytes engaging and crossing HEVs, and approaching and crossing the cortical lymphatic endothelium to enter the efferent lymph in live mice. C1 [Park, Chung; Hwang, Il-Young; Kehrl, John H.] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Park, C (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1064-3745 BN 978-1-4939-3480-5; 978-1-4939-3478-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1407 BP 195 EP 206 DI 10.1007/978-1-4939-3480-5_15 D2 10.1007/978-1-4939-3480-5 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG2YO UT WOS:000387780000016 PM 27271904 ER PT S AU Xu, XH Yun, M Wen, X Brzostowski, J Quan, W Wang, QJ Jin, T AF Xu, Xuehua Yun, Michelle Wen, Xi Brzostowski, Joseph Quan, Wei Wang, Q. Jane Jin, Tian BE Jin, T Hereld, D TI Quantitative Monitoring Spatiotemporal Activation of Ras and PKD1 Using Confocal Fluorescent Microscopy SO CHEMOTAXIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Confocal fluorescence microscopy; Ras activation; Protein kinase D1 ( PKD1); Phosphorylation of PKD1; Forsterresonance energy transfer ( FRET) ID PROTEIN-KINASE-D; PLECKSTRIN HOMOLOGY DOMAIN; SIGNALING EVENTS; LOOP SER(744); PHOSPHORYLATION; NEUTROPHILS; SLINGSHOT; PATHWAY; CELLS AB Receptor activation upon ligand binding induces activation of multiple signaling pathways. To fully understand how these signaling pathways coordinate, it is essential to determine the dynamic nature of the spatiotemporal activation profile of signaling components at the level of single living cells. Here, we outline a detailed methodology for visualizing and quantitatively measuring the spatiotemporal activation of Ras and PKD1 by applying advanced fluorescence imaging techniques, including multichannel, simultaneous imaging and Forster resonance energy transfer (FRET). C1 [Xu, Xuehua; Yun, Michelle; Wen, Xi; Quan, Wei; Jin, Tian] NIAID, Immunogenet Lab, Chemotaxis Signaling Sect, NIH, Rockville, MD 20852 USA. [Brzostowski, Joseph] NIAID, Imaging Core Facil, Immunogenet Lab, NIH, Rockville, MD USA. [Wang, Q. Jane] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. RP Xu, XH (reprint author), NIAID, Immunogenet Lab, Chemotaxis Signaling Sect, NIH, Rockville, MD 20852 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1064-3745 BN 978-1-4939-3480-5; 978-1-4939-3478-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1407 BP 307 EP 323 DI 10.1007/978-1-4939-3480-5_22 D2 10.1007/978-1-4939-3480-5 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG2YO UT WOS:000387780000023 PM 27271911 ER PT J AU Kiyatkin, EA Sharma, HS AF Kiyatkin, Eugene A. Sharma, Hari S. TI Breakdown of Blood-Brain and Blood-Spinal Cord Barriers During Acute Methamphetamine Intoxication: Role of Brain Temperature SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Review DE Brain edema; brain hyperthermia; cellular damage; methamphetamine; neurotoxicity; psychomotor stimulants; skin vasoconstriction ID NORMOTENSIVE YOUNG-RATS; CENTRAL-NERVOUS-SYSTEM; SUBSTITUTED AMPHETAMINES; INDUCED HYPERTHERMIA; REACTIVE GLIOSIS; NEURONAL DAMAGE; FREE-RADICALS; HEAT-STRESS; NEUROTOXICITY; DOPAMINE AB Methamphetamine (METH) is a powerful and often-abused stimulant with potent addictive and neurotoxic properties. While it is generally believed that structural brain damage induced by METH results from oxidative stress, in this work we present data suggesting robust disruption of blood-brain and blood-spinal cord barriers during acute METH intoxication in rats. We demonstrate the relationships between METH-induced brain hyperthermia and widespread but structure-specific barrier leakage, acute glial cell activation, changes in brain water and ionic homeostasis, and structural damage of different types of cells in the brain and spinal cord. Therefore, METH-induced leakage of the blood-brain and blood-spinal cord barriers is a significant contributor to different types of functional and structural brain abnormalities that determine acute toxicity of this drug and possibly neurotoxicity during its chronic use. C1 [Kiyatkin, Eugene A.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. [Sharma, Hari S.] Uppsala Univ, Univ Hosp, Dept Surg Sci, Uppsala, Sweden. RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov FU Intramural Research Program of NIDA-NIH; Leaderal Foundation for Acute Medicine, Stavanger, Norway; NIDA Distinguished International Scientist Collaboration Award (NIH) FX This study was supported by the Intramural Research Program of NIDA-NIH, the Leaderal Foundation for Acute Medicine, Stavanger, Norway, and NIDA Distinguished International Scientist Collaboration Award (NIH) to Hari S. Sharma. The authors greatly appreciate technical assistance in conducting experiments and data analyses of Mari-Anne Carlsson, Inga Horte (Uppsala University) and Leon P. Brown (NIDA-IRP), and valuable help in constructing color figures of Suraj Sharma (Uppsala University). NR 55 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL PI BUSUM PA PO BOX 294, BUSUM, 1400 AG, NETHERLANDS SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2016 VL 15 IS 9 BP 1129 EP 1138 DI 10.2174/1871527315666160920112445 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA EB1PJ UT WOS:000387125600010 PM 27658516 ER PT S AU Esser, L Zhou, F Yu, CA Xia, D AF Esser, Lothar Zhou, Fei Yu, Chang-An Xia, Di BE Cramer, WA Kallas, T TI Structure-Function Studies of the Cytochrome bc(1) Complex of Anoxygenic Photosynthetic Purple Bacteria SO CYTOCHROME COMPLEXES: EVOLUTION, STRUCTURES, ENERGY TRANSDUCTION, AND SIGNALING SE Advances in Photosynthesis and Respiration LA English DT Article; Book Chapter ID IRON-SULFUR PROTEIN; QUINOL OXIDATION SITE; INTERSUBUNIT DISULFIDE BOND; ELECTRON-TRANSFER REACTIONS; BOVINE HEART-MITOCHONDRIA; Q-CYCLE MECHANISM; X-RAY-STRUCTURE; RHODOBACTER-SPHAEROIDES; C REDUCTASE; Q(O) SITE AB Photosynthetic non-oxygenic purple bacteria possess various energy-conserving machineries that allow them to grow either photosynthetically, anaerobically or aerobically. The photosynthetic and respiratory branches of the power system in purple bacteria are connected via the cytochrome bc(1) complex (cyt bc(1)), which catalyzes electron transfer from quinol to cyt c and couples this reaction to proton translocation across the photosynthetic membrane, generating a trans-membrane proton gradient essential for various cellular activities including ATP synthesis. Crystal structures of wild-type and mutant cyt bc(1) complexes have been determined for the closely related photosynthetic bacteria R. sphaeroides and R. capsulatus in the presence of various inhibitors or substrates. These structures are remarkably similar to their mitochondrial counterparts but do feature insertions or deletions that are characteristic of the bacterial enzyme complexes. Thus, it is expected that bacterial cyt bc(1) complexes function in a manner similar to mitochondrial enzymes, justifying their use as model systems. The roles of insertions in bacterial cyt bc(1) function are discussed in relation to the subunit compositions of bacterial complexes and to mutagenesis studies. The mechanism of cyt bc(1) function is also discussed in the context of the architecture of quinol oxidation and quinone reduction sites, as revealed by inhibitor binding studies of both mitochondrial and bacterial bc(1) complexes. C1 [Esser, Lothar; Zhou, Fei; Xia, Di] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. [Yu, Chang-An] Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA. RP Xia, D (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM lesser@helix.nih.gov; fei.zhou@nih.gov; changan.yu@okstate.edu; xiad@mail.nih.gov NR 127 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1572-0233 BN 978-94-017-7481-9; 978-94-017-7479-6 J9 ADV PHOTOSYNTH RESP JI Adv. Photo. Respirat. PY 2016 VL 41 BP 209 EP 235 DI 10.1007/978-94-017-7481-9_10 D2 10.1007/978-94-017-7481-9 PG 27 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA BG2MW UT WOS:000387485400014 ER PT J AU Zhang, XY Justice, AC Hu, Y Wang, ZH Zhao, HY Wang, GL Johnson, EO Emu, B Sutton, RE Krystal, JH Xu, K AF Zhang, Xinyu Justice, Amy C. Hu, Ying Wang, Zuoheng Zhao, Hongyu Wang, Guilin Johnson, Eric O. Emu, Brinda Sutton, Richard E. Krystal, John H. Xu, Ke TI Epigenome-wide differential DNA methylation between HIV-infected and uninfected individuals SO EPIGENETICS LA English DT Article DE DNA methylation; Epigenome-wide association; HIV-1 infection; NLRC5; viral load ID DE-NOVO METHYLATION; I GENE-EXPRESSION; NF-KAPPA-B; T-CELLS; DOWN-REGULATION; EPIGENETIC REGULATION; NLRC5; AGE; GENOME; TRANSCRIPTION AB Epigenetic control of human immunodeficiency virus-1 (HIV-1) genes is critical for viral integration and latency. However, epigenetic changes in the HIV-1-infected host genome have not been well characterized. Here, we report the first large-scale epigenome-wide association study of DNA methylation for HIV-1 infection. We recruited HIV-infected (n = 261) and uninfected (n = 117) patients from the Veteran Aging Cohort Study (VACS) and all samples were profiled for 485,521 CpG sites in DNA extracted from the blood. After adjusting for cell type and clinical confounders, we identified 20 epigenome-wide significant CpGs for HIV-1 infection. Importantly, 2 CpGs in the promoter of the NLR family, CARD domain containing gene 5 (NLRC5), a key regulator of major histocompatibility complex class I gene expression, showed significantly lower methylation in HIV-infected subjects than in uninfected subjects (cg07839457: t = -6.03, P-nominal = 4.96 x 10(-9); cg16411857: t = -7.63, P-nominal = 3.07 x 10(-13)). Hypomethylation of these 2 CpGs was replicated in an independent sample (GSE67705: cg07839457: t = -4.44, P-nominal = 1.61 x 10(-5); cg16411857: t = -5.90; P = 1.99 x 10(-8)). Methylation of these 2 CpGs in NLRC5 was negatively correlated with viral load in the 2 HIV-infected samples (cg07839457: P = 1.8 x 10(-4); cg16411857: P = 0.03 in the VACS; and cg07839457: P = 0.04; cg164111857: P = 0.01 in GSE53840). Our findings demonstrate that differential DNA methylation is associated with HIV infection and suggest the involvement of a novel host gene, NLRC5, in HIV pathogenesis. C1 [Zhang, Xinyu; Krystal, John H.; Xu, Ke] Yale Univ, Sch Med, Dept Psychiat, 300 George St,Suite 901, New Haven, CT 06511 USA. [Zhang, Xinyu; Krystal, John H.; Xu, Ke] Connecticut Veteran Hlth Syst, West Haven, CT USA. [Justice, Amy C.] Yale Univ, Sch Med, New Haven Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. [Hu, Ying] NCI, Ctr Biomed Informat & Informat Technol, Bethesda, MD 20892 USA. [Wang, Zuoheng; Emu, Brinda; Sutton, Richard E.] Yale Univ, Sch Med, Dept Internal Med, Div Infect Dis, New Haven, CT 06511 USA. [Zhao, Hongyu] Yale Univ, Dept Biostat, Sch Publ Hlth, New Haven, CT 06511 USA. [Wang, Guilin] Yale Ctr Genom Anal, West Campus, Orange, CT USA. [Johnson, Eric O.] RTI Int, Fellow Program & Behav Hlth, Res Triangle Pk, NC USA. [Johnson, Eric O.; Xu, Ke] RTI Int, Criminal Justice Div, Res Triangle Pk, NC USA. RP Xu, K (reprint author), Yale Univ, Sch Med, Dept Psychiat, 300 George St,Suite 901, New Haven, CT 06511 USA. EM ke.xu@yale.edu RI Zhang, Xinyu/S-4946-2016 OI Zhang, Xinyu/0000-0001-8154-9334 FU National Institute on Drug Abuse [R03 DA039745, K12 DA000167, R01 DA038632, R01 DA042691]; National Institute on Alcoholism and Alcohol Abuse [R21AA022870]; National Center for Post-traumatic Stress Disorder FX The work was funded by the National Institute on Drug Abuse [R03 DA039745, K12 DA000167, R01 DA038632, R01 DA042691]; National Institute on Alcoholism and Alcohol Abuse [R21AA022870]; and National Center for Post-traumatic Stress Disorder. NR 54 TC 0 Z9 0 U1 2 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1559-2294 EI 1559-2308 J9 EPIGENETICS-US JI Epigenetics PY 2016 VL 11 IS 10 BP 750 EP 760 DI 10.1080/15592294.2016.1221569 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA EB3UM UT WOS:000387293900005 ER PT S AU Wang, SL Li, J Fang, JW AF Wang, Shu-Lin Li, Jin Fang, Jianwen BE Huang, DS Han, K Hussain, A TI Predicting Progression of ALS Disease with Random Frog and Support Vector Regression Method SO INTELLIGENT COMPUTING METHODOLOGIES, ICIC 2016, PT III SE Lecture Notes in Artificial Intelligence LA English DT Proceedings Paper CT 12th International Conference on Intelligent Computing (ICIC) CY AUG 02-05, 2016 CL Lanzhou, PEOPLES R CHINA SP IEEE Computat Intelligence Soc, Int Neural Network Soc, Natl Sci Fdn China DE Amyotrophic lateral sclerosis; Feature selection; Random frog; SVM ID AMYOTROPHIC-LATERAL-SCLEROSIS; SELECTION AB Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that involves the degeneration and death of the nerve cells in brain and spinal cord that control voluntary muscle movement. This disease can cause patients struggling with a progressive loss of motor function while typically leaving cognitive functions intact. This paper presents a novel predication method that combines a dimension reduction (integrating partial least square into random frog algorithm) with support vector regression to predict the progression of ALS in the next 3-12 months according to the data collected from the patients over the latest three months. The experiment on the actual data from the PRO-ACT database indicates that the proposed method is effective and robust and can predict the clinical outcome by means of the slope of ALS progression, as measured using the ALS functional rating scale (ALSFRS) and the score used for monitoring ALS patients. Especially, the features selected can effectively distinguish the clinical outcome targets. It is of great benefit to aid clinical care, identify new disease predictors and potentially significantly reduce the costs of future ALS clinical trials. C1 [Wang, Shu-Lin; Li, Jin] Hunan Univ, Coll Comp Sci & Elect Engn, Changsha 410082, Hunan, Peoples R China. [Fang, Jianwen] NCI, Div Canc Treatment & Diag, Rockville, MD 20850 USA. RP Wang, SL (reprint author), Hunan Univ, Coll Comp Sci & Elect Engn, Changsha 410082, Hunan, Peoples R China. EM smartforesting@gmail.com NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-42297-8; 978-3-319-42296-1 J9 LECT NOTES ARTIF INT PY 2016 VL 9773 BP 160 EP 170 DI 10.1007/978-3-319-42297-8_16 PG 11 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications SC Computer Science GA BG2KH UT WOS:000387430500016 ER PT J AU Osamor, PE Grady, C AF Osamor, Pauline E. Grady, Christine TI Women's autonomy in health care decision-making in developing countries: a synthesis of the literature SO INTERNATIONAL JOURNAL OF WOMENS HEALTH LA English DT Review DE women's autonomy; health decision-making; developing country; reproductive health; health care utilization ID REPRODUCTIVE HEALTH; FEMALE AUTONOMY; BREAST-CANCER; CONTRACEPTIVE USE; RURAL BANGLADESH; NEPAL; INVOLVEMENT; EMPOWERMENT; HUSBANDS; BEHAVIOR AB Autonomy is considered essential for decision-making in a range of health care situations, from health care seeking and utilization to choosing among treatment options. Evidence suggests that women in developing or low-income countries often have limited autonomy and control over their health decisions. A review of the published empirical literature to identify definitions and methods used to measure women's autonomy in developing countries describe the relationship between women's autonomy and their health care decision-making, and identify sociodemographic factors that influence women's autonomy and decision-making regarding health care was carried out. An integrated literature review using two databases (PubMed and Scopus) was performed. Inclusion criteria were 1) publication in English; 2) original articles; 3) investigations on women's decision-making autonomy for health and health care utilization; and 4) developing country context. Seventeen articles met inclusion criteria, including eleven from South Asia, five from Africa, and one from Central Asia. Most studies used a definition of autonomy that included independence for women to make their own choices and decisions. Study methods differed in that many used study-specific measures, while others used a set of standardized questions from their countries' national health surveys. Most studies examined women's autonomy in the context of reproductive health, while neglecting other types of health care utilized by women. Several studies found that factors, including age, education, and income, affect women's health care decision-making autonomy. Gaps in existing literature regarding women's autonomy and health care utilization include gaps in the areas of health care that have been measured, the influence of sex roles and social support, and the use of qualitative studies to provide context and nuance. C1 [Osamor, Pauline E.; Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bldg 10-1C118, Bethesda, MD 20892 USA. RP Osamor, PE (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10-1C118, Bethesda, MD 20892 USA. EM pauline.osamor@nih.gov NR 46 TC 2 Z9 2 U1 7 U2 7 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1179-1411 J9 IN J WOMENS HEALTH JI Int. J. Womens Health PY 2016 VL 8 BP 191 EP 202 DI 10.2147/IJWH.S105483 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA EB2RW UT WOS:000387210700002 PM 27354830 ER PT J AU Mondul, AM Moore, SC Weinstein, SJ Evans, AM Karoly, ED Mannisto, S Sampson, JN Albanes, D AF Mondul, Alison M. Moore, Steven C. Weinstein, Stephanie J. Evans, Anne M. Karoly, Edward D. Mannisto, Satu Sampson, Joshua N. Albanes, Demetrius TI Serum Metabolomic Response to Long-Term Supplementation with all-rac-alpha-Tocopheryl Acetate in a Randomized Controlled Trial SO JOURNAL OF NUTRITION AND METABOLISM LA English DT Article ID CAROTENE CANCER PREVENTION; GAMMA-TOCOPHEROL; VITAMIN-E; BETA-CAROTENE; PROSTATE-CANCER; CARBOXYETHYL-HYDROXYCHROMAN; HUMANS; METABOLITES; RISK; QUANTIFICATION AB Background. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a randomized controlled cancer prevention trial, showed a 32% reduction in prostate cancer incidence in response to vitamin E supplementation. Two other trials were not confirmatory, however. Objective. We compared the change in serum metabolome of the ATBC Study participants randomized to receive vitamin E to those who were not by randomly selecting 50 men from each of the intervention groups (50 mg/day all-rac-alpha-tocopheryl acetate (ATA), 20mg/day beta-carotene, both, placebo). Methods. Metabolomic profiling was conducted on baseline and follow-up fasting serum (Metabolon, Inc.). Results. After correction for multiple comparisons, five metabolites were statistically significantly altered (beta is the change in metabolite level expressed as number of standard deviations on the log scale): alpha-CEHC sulfate (beta = 1.51, p = 1.45 x 10(-38)), alpha-CEHC glucuronide (beta = 1.41, p = 1.02 x 10(-31)), alpha-tocopherol (beta = 0.97, p = 2.22 x 10 -13), gamma-tocopherol (beta = -0.90, p = 1.76 x 10(-11)), and beta-tocopherol (p = -0.73, p = 9.40 x 10(-8)). Glutarylcarnitine, beta-alanine, ornithine, and N6-acetyllysine were also decreased by ATA supplementation (beta range 0.40 to -0.36), but not statistically significantly. Conclusions. Comparison of the observed metabolite alterations resulting from ATA supplementation to those in other vitamin E trials of different populations, dosages, or formulations may shed light on the apparently discordant vitamin E-prostate cancer risk findings. C1 [Mondul, Alison M.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Moore, Steven C.; Weinstein, Stephanie J.; Albanes, Demetrius] NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NIH,Nutr Epidemiol Branch, Bethesda, MD 20892 USA. [Evans, Anne M.; Karoly, Edward D.] Metabolon Inc, Durham, NC USA. [Mannisto, Satu] Natl Inst Hlth andWelfare, Dept Chron Dis Prevent, Helsinki, Finland. [Sampson, Joshua N.] NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NIH,Biostat Branch, Bethesda, MD USA. RP Mondul, AM (reprint author), Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. EM amondul@umich.edu NR 31 TC 0 Z9 0 U1 1 U2 1 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2090-0724 EI 2090-0732 J9 J NUTR METAB JI J. Nutr. Metab. PY 2016 AR 6158436 DI 10.1155/2016/6158436 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA EB3SV UT WOS:000387287000001 ER PT S AU Cheng, RD Roth, HR Lu, L Wang, SJ Turkbey, B Gandler, W McCreedy, ES Agarwal, HK Choyke, P Summers, RM McAuliffe, MJ AF Cheng, Ruida Roth, Holger R. Lu, Le Wang, Shijun Turkbey, Baris Gandler, William McCreedy, Evan S. Agarwal, Harsh K. Choyke, Peter Summers, Ronald M. McAuliffe, Matthew J. BE Styner, MA Angelini, ED TI Active Appearance Model and Deep Learning for More Accurate Prostate Segmentation on MRI SO MEDICAL IMAGING 2016: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY MAR 01-03, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, imXPAD DE Machine Learning; Active Appearance Model; Deep Learning; MRI; Prostate segmentation AB Prostate segmentation on 3D MR images is a challenging task due to image artifacts, large inter-patient prostate shape and texture variability, and lack of a clear prostate boundary specifically at apex and base levels. We propose a supervised machine learning model that combines atlas based Active Appearance Model (AAM) with a Deep Learning model to segment the prostate on MR images. The performance of the segmentation method is evaluated on 20 unseen MR image datasets. The proposed method combining AAM and Deep Learning achieves a mean Dice Similarity Coefficient (DSC) of 0.925 for whole 3D MR images of the prostate using axial cross-sections. The proposed model utilizes the adaptive atlas-based AAM model and Deep Learning to achieve significant segmentation accuracy. C1 [Cheng, Ruida; Gandler, William; McCreedy, Evan S.; McAuliffe, Matthew J.] NIH, Imaging Sci Lab, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. [Roth, Holger R.; Lu, Le; Wang, Shijun; Summers, Ronald M.] NIH, Imaging Biomarkers & CAD Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Turkbey, Baris; Agarwal, Harsh K.; Choyke, Peter] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. RP Cheng, RD (reprint author), NIH, Imaging Sci Lab, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0019-5 J9 PROC SPIE PY 2016 VL 9784 AR 97842I DI 10.1117/12.2216286 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BF5NM UT WOS:000382313300088 ER PT S AU Huo, Y Carass, A Resnick, SM Pham, DL Prince, JL Landman, BA AF Huo, Yuankai Carass, Aaron Resnick, Susan M. Pham, Dzung L. Prince, Jerry L. Landman, Bennett A. BE Styner, MA Angelini, ED TI Combining Multi-atlas Segmentation with Brain Surface Estimation SO MEDICAL IMAGING 2016: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY MAR 01-03, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, imXPAD DE Multi-atlas Segmentation; Magnetic Resonance Imaging; Cerebral Cortex; Cortical Reconstruction ID HUMAN CEREBRAL-CORTEX; IMAGE SEGMENTATION; RECONSTRUCTION; ALGORITHM; VALIDATION; FUSION AB Whole brain segmentation (with comprehensive cortical and subcortical labels) and cortical surface reconstruction are two essential techniques for investigating the human brain. The two tasks are typically conducted independently, however, which leads to spatial inconsistencies and hinders further integrated cortical analyses. To obtain self-consistent whole brain segmentations and surfaces, FreeSurfer segregates the subcortical and cortical segmentations before and after the cortical surface reconstruction. However, this "segmentation to surface to parcellation" strategy has shown limitations in various situations. In this work, we propose a novel "multi-atlas segmentation to surface" method called Multi-atlas CRUISE (MaCRUISE), which achieves self-consistent whole brain segmentations and cortical surfaces by combining multi-atlas segmentation with the cortical reconstruction method CRUISE. To our knowledge, this is the first work that achieves the reliability of state-of-the-art multi-atlas segmentation and labeling methods together with accurate and consistent cortical surface reconstruction. Compared with previous methods, MaCRUISE has three features: (1) MaCRUISE obtains 132 cortical/subcortical labels simultaneously from a single multi-atlas segmentation before reconstructing volume consistent surfaces; (2) Fuzzy tissue memberships are combined with multi-atlas segmentations to address partial volume effects; (3) MaCRUISE reconstructs topologically consistent cortical surfaces by using the sulci locations from multi-atlas segmentation. Two data sets, one consisting of five subjects with expertly traced landmarks and the other consisting of 100 volumes from elderly subjects are used for validation. Compared with CRUISE, MaCRUISE achieves self-consistent whole brain segmentation and cortical reconstruction without compromising on surface accuracy. MaCRUISE is comparably accurate to FreeSurfer while achieving greater robustness across an elderly population. C1 [Huo, Yuankai; Landman, Bennett A.] Vanderbilt Univ, Elect Engn, 221 Kirkland Hall, Nashville, TN 37235 USA. [Carass, Aaron; Prince, Jerry L.] Johns Hopkins Univ, Image Anal & Commun Lab, Baltimore, MD USA. [Resnick, Susan M.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA. [Pham, Dzung L.] Henry Jackson Fdn, Ctr Neurosci & Regenerat Med, Bethesda, MD USA. RP Huo, Y (reprint author), Vanderbilt Univ, Elect Engn, 221 Kirkland Hall, Nashville, TN 37235 USA. OI Carass, Aaron/0000-0003-4939-5085 NR 22 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0019-5 J9 PROC SPIE PY 2016 VL 9784 AR 97840E DI 10.1117/12.2216604 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BF5NM UT WOS:000382313300013 ER PT J AU Sektioglu, IM Carretero, R Bender, N Bogdan, C Garbi, N Umansky, V Umansky, L Urban, K von Knebel-Doberitz, M Somasundaram, V Wink, D Beckhove, P Hammerling, GJ AF Sektioglu, Ibrahim M. Carretero, Rafael Bender, Noemi Bogdan, Christian Garbi, Natalio Umansky, Viktor Umansky, Ludmila Urban, Katharina von Knebel-Doeberitz, Magnus Somasundaram, Veena Wink, David Beckhove, Philipp Haemmerling, Guenter J. TI Macrophage-derived nitric oxide initiates T-cell diapedesis and tumor rejection SO ONCOIMMUNOLOGY LA English DT Article DE Adoptive T-cell transfer; endothelial adhesion molecules; endothelial barrier; iNOS plus macrophage; NO; tumor therapy; T-cell infiltration ID NF-KAPPA-B; PANCREATIC-CANCER; ENDOTHELIAL-CELLS; EXPRESSION; INFILTRATION; MICE; INHIBITION; SYNTHASE; THERAPY; DIFFERENTIATION AB In tumor biology, nitric oxide (NO) is generally regarded as an immunosuppressive molecule that impedes T-cell functions and activation of endothelial cells. Contrasting with this view, we here describe a critical role for NO derived from inducible nitric oxide (iNOS)-expressing tumor macrophages in T-cell infiltration and tumor rejection as shown by iNOS gene deletion, inhibition of iNOS, or NO donors. Specifically, macrophage-derived NO was found to induce on tumor vessels adhesion molecules that were required for T-cell extravasation. Experiments with human endothelial cells revealed a bimodal dose-dependent effect of NO. High doses of NO donors were indeed suppressive but lower, more physiological concentrations, induced adhesion molecules in an NFkB-dependent pathway and preferentially activated transcription of genes involved in lymphocyte diapedesis. iNOS(+) macrophages in tumors appear to generate precisely the amount of NO that promotes endothelial activation and T-cell infiltration. These results will be valuable for the development of strategies designed to overcome the paucity of T-cell infiltration into tumors that is a major obstacle in clinical cancer immunotherapy. C1 [Sektioglu, Ibrahim M.; Carretero, Rafael; Bender, Noemi; Beckhove, Philipp; Haemmerling, Guenter J.] German Canc Res Ctr, Tumor Immunol Program, Heidelberg, Germany. [Bogdan, Christian] Friedrich Alexander Univ FAU Erlangen Nurnberg, Univklinikum Erlangen, Mikrobiol Inst Klin Mikrobiol Immunol & Hyg, Erlangen, Germany. [Garbi, Natalio] Univ Bonn, Inst Mol Med & Expt Immunol, Bonn, Germany. [Umansky, Viktor] German Canc Res Ctr, Skin Canc Unit, Heidelberg, Germany. [Umansky, Viktor] Ruprecht Karl Univ Heidelberg, Univ Med Ctr Mannheim, Dept Dermatol Venereol & Allergol, Mannheim, Germany. [Umansky, Ludmila; Urban, Katharina] German Canc Res Ctr, Immune Monitoring Unit, Heidelberg, Germany. [von Knebel-Doeberitz, Magnus] German Canc Res Ctr, Clin Cooperat Unit, Heidelberg, Germany. [von Knebel-Doeberitz, Magnus] Heidelberg Univ, Dept Appl Tumor Biol Inst Pathol, Heidelberg, Germany. [Somasundaram, Veena; Wink, David] Natl Canc Inst, Canc & Inflammat Program, NIH, Frederick, MD USA. [Beckhove, Philipp] Regensburg Ctr Intervent Immunol RCI, Regensburg, Germany. [Beckhove, Philipp] Univ Med Ctr Regensburg, Regensburg, Germany. RP Hammerling, GJ (reprint author), German Canc Res Ctr, Tumor Immunol Program D030, Neuenheimer Feld 280, Heidelberg, Germany. EM hammerling@dkfz.de FU Wilhelm Sander-Stiftung; Deutsche Forschungsgemeinschaft [SFB 704, SFB 643, SFB 1181]; Interdisciplinary Center for Clinical Research of the University Hospital Erlangen [A61] FX G.J.H. was supported by the Wilhelm Sander-Stiftung, N.G. by the Deutsche Forschungsgemeinschaft (SFB 704, and C.B. by the Deutsche Forschungsgemeinschaft (SFB 643 and SFB 1181) and the Interdisciplinary Center for Clinical Research of the University Hospital Erlangen (project A61). NR 40 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 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 10 AR e1204506 DI 10.1080/2162402X.2016.1204506 PG 13 WC Oncology; Immunology SC Oncology; Immunology GA EB3NI UT WOS:000387271300005 PM 27853636 ER PT J AU Pinkerton, LE Hein, MJ Anderson, JL Little, MP Sigurdson, AJ Schubauer-Berigan, MK AF Pinkerton, Lynne E. Hein, Misty J. Anderson, Jeri L. Little, Mark P. Sigurdson, Alice J. Schubauer-Berigan, Mary K. TI Breast cancer incidence among female flight attendants: exposure-response analyses SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE airline attendant; circadian rhythm disruption; cohort study; cosmic ionizing radiation ID CIRCADIAN-RHYTHM DISRUPTION; AIRLINE CABIN ATTENDANTS; COSMIC-RADIATION; BOMB SURVIVORS; RISK; COHORT; METAANALYSIS; ICELAND; CREW AB Objective The aim of this study was to examine the association of breast cancer incidence with cosmic radiation dose and circadian rhythm disruption in a cohort of 6093 US female flight attendants. Methods The association of breast cancer risk with cumulative cosmic radiation dose, time spent working during the standard sleep interval, and time zones crossed (all lagged by ten years), adjusted for non-occupational breast cancer risk factors, was evaluated using Cox regression. Individual exposure estimates were derived from work history data and domicile-and era-specific exposure estimates. Breast cancers were identified from telephone interviews and state cancer registries, and covariate data were obtained from telephone interviews. Results Breast cancer incidence in the overall cohort was not associated with exposure. Positive associations in breast cancer incidence were observed with all three exposures only among the 884 women with parity of >= 3. Adjusted excess relative risks for women with parity of >= 3 were 1.6 [95% confidence interval (95% CI) 0.14-6.6], 0.99 (95% CI -0.04-4.3), and 1.5 (95% CI 0.14-6.2) per 10 mGy, per 2000 hours spent working in the standard sleep interval, and per 4600 time zones crossed (the approximate means of the fourth exposure quintiles among breast cancer cases), respectively. Conclusions Positive exposure-response relations, although observed only in a small subset of the cohort, were robust. Future studies of breast cancer incidence among other workers with circadian rhythm disruption should assess interaction with parity to see if our findings are confirmed. C1 [Pinkerton, Lynne E.; Anderson, Jeri L.; Schubauer-Berigan, Mary K.] NIOSH, Industrywide Studies Branch, Div Surveillance Hazard Evaluat & Field Studies, 1090 Tusculum Ave,R-15, Cincinnati, OH 45226 USA. [Hein, Misty J.] CACI Inc, Cincinnati, OH USA. [Little, Mark P.; Sigurdson, Alice J.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Pinkerton, LE (reprint author), NIOSH, Industrywide Studies Branch, Div Surveillance Hazard Evaluat & Field Studies, 1090 Tusculum Ave,R-15, Cincinnati, OH 45226 USA. EM lep5@cdc.gov FU National Cancer Institute; Office of Women's Health of the US Department of Health and Human Services; Division of Cancer Epidemiology and Genetics, National Cancer Institute; National Institute for Occupational Safety and Health FX The study was funded, in part, by an interagency agreement with the National Cancer Institute and by the Office of Women's Health of the US Department of Health and Human Services. The research was also supported in part by the intramural research programs of the Division of Cancer Epidemiology and Genetics, National Cancer Institute and the National Institute for Occupational Safety and Health. NR 27 TC 0 Z9 0 U1 6 U2 6 PU SCANDINAVIAN JOURNAL WORK ENVIRONMENT & HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 EI 1795-990X J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PY 2016 VL 42 IS 6 BP 538 EP 546 DI 10.5271/sjweh.3586 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EB6AR UT WOS:000387463400010 PM 27551752 ER PT J AU de Jong, J Schoenmaker, B van Zanten, J AF de Jong, Jurrien Schoenmaker, Ben van Zanten, Jeroen TI 'BataiIle a boire': Two centuries of Waterloo historiography SO TIJDSCHRIFT VOOR GESCHIEDENIS LA Dutch DT Article DE Waterloo; heritage and memory; historiography; re-enactment AB The bicentennial celebrations in 2015 of the Battle of Waterloo have rekindled public interest in the history and heritage of this historical event. The commemoration also led to a massive increase in publications. Many of these are based on new sources (ego-documents, archaeological finds, and archival sources) discovered in the last decades. These new sources have allowed historians to move away from official accounts and towards a view from below. This approach has added significantly to our understanding of the battle, but in some cases the new sources have caused confusion and led to new historiographical controversies, both on a national and transnational level. At the same time historians in and outside academia are moving beyond national histories of the battle to more balanced and transnational accounts. Recent interest in heritage and memory has resulted in new research on the appropriation of Waterloo by various interested parties. At the same time it is to be regretted that academic historians almost exclusively focus on heritage and memory and have been neglecting the story of the battle. As a result they have been largely absent during the commemorations. Public interest in Waterloo has been mostly served by popular historical publications and reenactment events. C1 [de Jong, Jurrien] Cent Bur Stat, Heerlen, Netherlands. [Schoenmaker, Ben] NIMH, Mil Geschiedenis, Bethesda, MD 20892 USA. [Schoenmaker, Ben] Leiden Univ, NL-2300 RA Leiden, Netherlands. [van Zanten, Jeroen] Univ Amsterdam, UD Moderne Geschiedenis, NL-1012 WX Amsterdam, Netherlands. RP de Jong, J (reprint author), Cent Bur Stat, Heerlen, Netherlands. EM jongjde@gmail.com; b.schoenmaker@hum.leidenuniv.nl; j.c.vanzanten@uva.nl NR 57 TC 0 Z9 0 U1 0 U2 0 PU WOLTERS-NOORDHOFF B V PI GRONINGEN PA BOX 58, 9700 GRONINGEN, NETHERLANDS SN 0040-7518 J9 TIJDSCHR GESCHIEDEN JI Tijdschr. Geschied. PY 2016 VL 129 IS 3 BP 415 EP 432 DI 10.5117/TVGESCH2016.3JONG PG 18 WC History SC History GA EB3XN UT WOS:000387302600004 ER PT S AU Kovacs, W Liu, CY Summers, RM Yao, JH AF Kovacs, William Liu, Chia-Ying Summers, Ronald M. Yao, Jianhua GP IEEE TI IDENTIFICATION OF MUSCLE AND SUBCUTANEOUS AND INTERMUSCULAR ADIPOSE TISSUE ON THIGH MRI OF MUSCULAR DYSTROPHY SO 2016 IEEE 13TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 13th International Symposium on Biomedical Imaging (ISBI) CY APR 13-16, 2016 CL Prague, CZECH REPUBLIC SP IEEE, EMB, IEEE Signal Proc Soc, Amer Elements ID SEGMENTATION AB Muscular dystrophies can affect the muscle distribution within the legs. In order to effectively study and track disease progression, it is important to quantify both muscle and fat volumes, and distinguish between subcutaneous ( SAT) and intermuscular adipose tissue (IMAT). While several techniques have been previously described that perform such classification, they rely heavily on the muscle location, and so may not be suitable for differentiating SAT and IMAT in severe cases of dystrophy. We propose a method that utilizes muscle location if available, but also identifies the fascia lata to serve as the boundary between SAT and IMAT. Our method achieved DICE coefficients of 0.93, 0.88, and 0.68 for muscle, SAT, and IMAT, respectively, in mild cases, of 0.94, 0.91, and 0.85 in moderate cases, and of 0.79, 0.90, and 0.91 in severe cases. C1 [Kovacs, William; Liu, Chia-Ying; Summers, Ronald M.; Yao, Jianhua] NIH, Clin Image Proc Serv, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. RP Kovacs, W (reprint author), NIH, Clin Image Proc Serv, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4799-2349-6; 978-1-4799-2350-2 J9 I S BIOMED IMAGING PY 2016 BP 176 EP 179 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BG0MT UT WOS:000386377400042 ER PT S AU Liu, JM Wang, D Wei, ZS Lu, L Kim, L Turkbey, E Summers, RM AF Liu, Jiamin Wang, David Wei, Zhuoshi Lu, Le Kim, Lauren Turkbey, Evrim Summers, Ronald M. GP IEEE TI COLITIS DETECTION ON COMPUTED TOMOGRAPHY USING REGIONAL CONVOLUTIONAL NEURAL NETWORKS SO 2016 IEEE 13TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 13th International Symposium on Biomedical Imaging (ISBI) CY APR 13-16, 2016 CL Prague, CZECH REPUBLIC SP IEEE, EMB, IEEE Signal Proc Soc, Amer Elements DE Colitis; Region proposal; CNNs; SVM ID IMAGE SEGMENTATION; DIAGNOSIS; CT AB Colitis is inflammation of the colon that is frequently associated with infection and immune compromise. The wall of a colon afflicted with colitis is much thicker than normal. Colitis can be debilitating or life threatening, and early detection is essential to initiate proper treatment. In this work, we apply high-capacity convolutional neural net-works (CNNs) to bottom-up region proposals to detect potential colitis on CT scans. Our method first generates around 3000 category-independent region proposals for each slice of the input CT scan using selective search. Then, a fixed-length feature vector is extracted from each region proposal using a CNN. Finally, each region proposal is classified and assigned a confidence score with a linear SVM. We applied the detection method to 448 images from 56 CT scans of patients with colitis for evaluation. The detection system achieved 85% sensitivity at 1 false positive per image. C1 [Liu, Jiamin; Wang, David; Wei, Zhuoshi; Lu, Le; Kim, Lauren; Turkbey, Evrim; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10,Room 1C224 MSC 1182, Bethesda, MD 20892 USA. RP Liu, JM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10,Room 1C224 MSC 1182, Bethesda, MD 20892 USA. NR 20 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4799-2349-6; 978-1-4799-2350-2 J9 I S BIOMED IMAGING PY 2016 BP 863 EP 866 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BG0MT UT WOS:000386377400204 ER PT S AU Lesage, D Pizaine, G Miyayama, S Kobeiter, H Wood, BJ Mielekamp, P van der Sterren, W Radaelli, A AF Lesage, David Pizaine, Guillaume Miyayama, Shiro Kobeiter, Hicham Wood, Bradford J. Mielekamp, Peter van der Sterren, William Radaelli, Alessandro GP IEEE TI VIRTUAL PARENCHYMAL PERFUSION FOR SELECTIVE INTRA-ARTERIAL THERAPY OF LIVER CANCER SO 2016 IEEE 13TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 13th International Symposium on Biomedical Imaging (ISBI) CY APR 13-16, 2016 CL Prague, CZECH REPUBLIC SP IEEE, EMB, IEEE Signal Proc Soc, Amer Elements DE Liver cancer; interventional radiology; planning; virtual perfusion AB Intra-arterial injection of therapeutic agents is among the most common options for unresectable liver cancer. Such procedures rely on an in-depth assessment of the vessels leading to the tumor(s) to select the optimal catheter location maximizing therapy selectivity and potency while limiting healthy liver toxicity. In this paper, we propose a Virtual parenchymal Perfusion (VP) algorithm to approximate distal liver vascular territories given prospective "virtual" injection points, with all predictive data derived from a single 3D arterial Cone Beam Computed Tomography (CBCT) scan. Vascular territories are extracted from a vessel-driven geodesic distance map computed from the user-selected injection position, without the need for explicit vessel segmentation. In order to evaluate our approach, we compared liver sub-territories segmented from actual CBCT scans after selective injection of contrast agent or lipiodol, with the vascular territories computed with the VP algorithm using the non-selective arterial CBCT scans. Results on 11 pairs of arterial and selective injection CBCT scans showed a non-significant difference between virtual and real segmented volumes (p=0.73), an average mean distance of 4.75 m m, an average volume error of 16% and an average Dice coefficient of 0.75, supporting a high correlation. This study demonstrates the potential of our VP algorithm in planning intra-arterial therapy of liver cancer and provides the basis for clinical translation in a live interventional context. C1 [Lesage, David; Pizaine, Guillaume] Philips Res, Suresnes, France. [Miyayama, Shiro] Fukui Ken Saisekai Hosp, Dept Diagnost Radiol, Fukui, Japan. [Kobeiter, Hicham] Henri Mondor Univ Hosp, Dept Med Imaging, Creteil, France. [Wood, Bradford J.] NIH, Ctr Intervent Oncol, Ctr Clin, Bethesda, MD 20892 USA. [Wood, Bradford J.] NCI, Bethesda, MD 20892 USA. [Mielekamp, Peter; van der Sterren, William; Radaelli, Alessandro] Philips, Image Guided Therapy Syst, Best, Netherlands. RP Lesage, D (reprint author), Philips Res, Suresnes, France. NR 8 TC 0 Z9 0 U1 2 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4799-2349-6; 978-1-4799-2350-2 J9 I S BIOMED IMAGING PY 2016 BP 1147 EP 1150 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BG0MT UT WOS:000386377400271 ER PT S AU Wang, YN Yao, JH Burns, JE Summers, RM AF Wang, Yinong Yao, Jianhua Burns, Joseph E. Summers, Ronald M. GP IEEE TI OSTEOPOROTIC AND NEOPLASTIC COMPRESSION FRACTURE CLASSIFICATION ON LONGITUDINAL CT SO 2016 IEEE 13TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 13th International Symposium on Biomedical Imaging (ISBI) CY APR 13-16, 2016 CL Prague, CZECH REPUBLIC SP IEEE, EMB, IEEE Signal Proc Soc, Amer Elements DE vertebral compression fracture; classification; osteoporotic; neoplastic ID VERTEBRAL BODY; SPINE AB Classification of vertebral compression fractures (VCF) having osteoporotic or neoplastic origin is fundamental to the planning of treatment. We developed a fracture classification system by acquiring quantitative morphologic and bone density determinants of fracture progression through the use of automated measurements from longitudinal studies. A total of 250 CT studies were acquired for the task, each having previously identified VCFs with osteoporosis or neoplasm. Thirty-six features for each identified VCF were computed and classified using a committee of support vector machines. Ten-fold cross validation on 695 identified fractured vertebrae showed classification accuracies of 0.812, 0.665, and 0.820 for the measured, longitudinal, and combined feature sets respectively. C1 [Wang, Yinong; Yao, Jianhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Burns, Joseph E.] Univ Calif Irvine, Dept Radiol Sci, Sch Med, Irvine, CA 92717 USA. RP Wang, YN (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4799-2349-6; 978-1-4799-2350-2 J9 I S BIOMED IMAGING PY 2016 BP 1181 EP 1184 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BG0MT UT WOS:000386377400279 ER PT S AU Gao, MC Xu, ZY Lu, L Wu, A Nogues, I Summers, RM Mollura, DJ AF Gao, Mingchen Xu, Ziyue Lu, Le Wu, Aaron Nogues, Isabella Summers, Ronald M. Mollura, Daniel J. GP IEEE TI SEGMENTATION LABEL PROPAGATION USING DEEP CONVOLUTIONAL NEURAL NETWORKS AND DENSE CONDITIONAL RANDOM FIELD SO 2016 IEEE 13TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 13th International Symposium on Biomedical Imaging (ISBI) CY APR 13-16, 2016 CL Prague, CZECH REPUBLIC SP IEEE, EMB, IEEE Signal Proc Soc, Amer Elements DE Segmentation Label Propagation; Dense Conditional Random Field; Convolutional Neural Network; Interstitial Lung Disease; Multi-class Labeling AB Availability and accessibility of large-scale annotated medical image datasets play an essential role in robust supervised learning of medical image analysis. Missed labeling of regions of interest is a common issue on existing medical image datasets due to the labor intensive nature of the annotation task which requires high levels of clinical proficiency. In this paper, we present a segmentation based label propagation method to a publicly available dataset on interstitial lung disease [3], to address the missing annotation challenge. Upon validation from an expert radiologist, the amount of available annotated training data is largely increased. Such a dataset expansion can can potentially increase the accuracy of Computer-aided Detection (CAD) systems. The proposed constrained segmentation propagation algorithm combines the cues from the initial annotations, deep convolutional neural networks and a dense fully-connected Conditional Random Field (CRF) that achieves high quantitative accuracy levels. C1 [Gao, Mingchen; Xu, Ziyue; Lu, Le; Wu, Aaron; Nogues, Isabella; Summers, Ronald M.; Mollura, Daniel J.] NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. RP Xu, ZY (reprint author), NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. EM ziyue.xu@nih.gov NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4799-2349-6; 978-1-4799-2350-2 J9 I S BIOMED IMAGING PY 2016 BP 1265 EP 1268 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BG0MT UT WOS:000386377400299 ER PT S AU Badoual, A Gerard, M de Leener, B Abi-Jaoudeh, N Kadoury, S AF Badoual, Anais Gerard, Maxime de Leener, Benjamin Abi-Jaoudeh, Nadine Kadoury, Samuel GP IEEE TI 3D VASCULAR PATH PLANNING OF CHEMO-EMBOLIZATIONS USING SEGMENTED HEPATIC ARTERIES FROM MR ANGIOGRAPHY SO 2016 IEEE 13TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 13th International Symposium on Biomedical Imaging (ISBI) CY APR 13-16, 2016 CL Prague, CZECH REPUBLIC SP IEEE, EMB, IEEE Signal Proc Soc, Amer Elements DE Liver cancer; transcatheter arterial chemoembolization; vascular path planning; hepatic artery segmentation; magnetic resonance angiography ID EXTRACTION AB Transcatheter arterial chemo-embolization (TACE) is a therapeutic procedure to treat primary and metastatic liver cancer. It requires prior delineation of the hepatic arteries on magnetic resonance angiography (MRA) data and identification of the vessels supplying the tumor. Manual segmentation is extremely challenging and time consuming, thereby increasing the risk of wrongfully identifying the feeding vessels. We present a vascular path planning tool for TACE procedures by automatically segmenting the hepatic arteries on MRA. The proposed method first detects the celiac trunk from the aorta, then localizes and tags bifurcations throughout the arterial network for path planning. The algorithm is based on a multiple hypothesis tracking approach used to propagate deformable mesh surfaces. We validated the proposed framework on 20 liver-cancerpatients using abdominal MRA with 20 seconds delay after contrast injection. We show that the algorithm improves the selectivity of the arterial segments and outperforms two state-of-the-art methods with respect to manual segmentation, yielding mesh geometries with a mean absolute distance of 0.61 +/- 0.10 mm for 3D mesh models. C1 [Badoual, Anais; Gerard, Maxime; Kadoury, Samuel] Ecole Polytech Montreal, MedICAL, Montreal, PQ, Canada. [Abi-Jaoudeh, Nadine] NIH, Rad & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. [Gerard, Maxime; de Leener, Benjamin; Kadoury, Samuel] Polytech Montreal, Inst Biomed Engn, Montreal, PQ, Canada. [Badoual, Anais] Ecole Polytech Fed Lausanne, Biomed Imaging Grp, CH-1015 Lausanne, Switzerland. RP Badoual, A (reprint author), Ecole Polytech Montreal, MedICAL, Montreal, PQ, Canada.; Badoual, A (reprint author), Ecole Polytech Fed Lausanne, Biomed Imaging Grp, CH-1015 Lausanne, Switzerland. NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4799-2349-6; 978-1-4799-2350-2 J9 I S BIOMED IMAGING PY 2016 BP 1346 EP 1349 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BG0MT UT WOS:000386377400318 ER PT S AU Wu, AR Xu, ZY Gao, MC Buty, M Mollura, DJ AF Wu, Aaron Xu, Ziyue Gao, Mingchen Buty, Mario Mollura, Daniel J. GP IEEE TI DEEP VESSEL TRACKING: A GENERALIZED PROBABILISTIC APPROACH VIA DEEP LEARNING SO 2016 IEEE 13TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 13th International Symposium on Biomedical Imaging (ISBI) CY APR 13-16, 2016 CL Prague, CZECH REPUBLIC SP IEEE, EMB, IEEE Signal Proc Soc, Amer Elements DE Vascular Structure; Deep Learning; Principal Component Analysis; Nearest Neighbor Search; Generalized Probabilistic Tracking ID SEGMENTATION; IMAGES; CT AB Analysis of vascular geometry is important in many medical imaging applications, such as retinal, pulmonary, and cardiac investigations. In order to make reliable judgments for clinical usage, accurate and robust segmentation methods are needed. Due to the high complexity of biological vasculature trees, manual identification is often too time-consuming and tedious to be used in practice. To design an automated and computerized method, a major challenge is that the appearance of vasculatures in medical images has great variance across modalities and subjects. Therefore, most existing approaches are specially designed for a particular task, lacking the flexibility to be adapted to other circumstances. In this paper, we present a generic approach for vascular structure identification from medical images, which can be used for multiple purposes robustly. The proposed method uses the state-of-the-art deep convolutional neural network (CNN) to learn the appearance features of the target. A Principal Component Analysis (PCA)-based nearest neighbor search is then utilized to estimate the local structure distribution, which is further incorporated within the generalized probabilistic tracking framework to extract the entire connected tree. Qualitative and quantitative results over retinal fundus data demonstrate that the proposed framework achieves comparable accuracy as compared with state-of-the-art methods, while efficiently producing more information regarding the candidate tree structure. C1 [Wu, Aaron; Xu, Ziyue; Gao, Mingchen; Buty, Mario; Mollura, Daniel J.] NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. RP Xu, ZY (reprint author), NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. EM ziyue.xu@nih.gov NR 10 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4799-2349-6; 978-1-4799-2350-2 J9 I S BIOMED IMAGING PY 2016 BP 1363 EP 1367 PG 5 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BG0MT UT WOS:000386377400322 ER PT J AU Nakata, R Clemens, S Martin, D Jaquiro, C Lubecke, V AF Nakata, Robert Clemens, Scott Martin, Daren Jaquiro, Charles Lubecke, Victor GP IEEE TI Unmanned Aerial Vehicle Platform Stabilization for Remote Radar Life Sensing SO 2016 IEEE/ACES INTERNATIONAL CONFERENCE ON WIRELESS INFORMATION TECHNOLOGY AND SYSTEMS (ICWITS) AND APPLIED COMPUTATIONAL ELECTROMAGNETICS (ACES) LA English DT Proceedings Paper CT IEEE/ACES International Conference on Wireless Information Technology (ICWITS) and System and Applied Computational Electromagnetics (ACES) CY MAR 13-17, 2016 CL Honolulu, HI SP IEEE Antennas & Propagat Soc, Appl Computat Electromagnet Soc, IEEE DE remote sensing; radar; UAV; motion compensation AB Unmanned Aerial Vehicle (UAV) platforms are increasingly ubiquitous and an ideal platform for rapid deployment to conduct remote sensing. However, for radar sensors that measure the phase of the signal of interest, the platform must be stabilized to avoid signal distortion. Measurement of respiratory motion with a continuous wave Doppler radar sensor is vulnerable to platform motion and requires a stable platform and post-detection motion compensation signal processing. We have investigated feedback stabilization techniques via simulation and empirical measurements using a bench top test fixture to remove the motion noise. C1 [Nakata, Robert; Clemens, Scott; Martin, Daren; Jaquiro, Charles; Lubecke, Victor] Univ Hawaii Manoa, Dept Elect Engn, Honolulu, HI 96822 USA. NIMHD, NIH, NSF, New York, NY USA. RP Nakata, R (reprint author), Univ Hawaii Manoa, Dept Elect Engn, Honolulu, HI 96822 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-5090-1259-6 PY 2016 PG 2 WC Computer Science, Theory & Methods; Engineering, Electrical & Electronic; Telecommunications SC Computer Science; Engineering; Telecommunications GA BG0WM UT WOS:000386537100090 ER PT S AU Amresh, A Sinha, M Salla, R Birr, R AF Amresh, Ashish Sinha, Madhumita Salla, Rahul Birr, Rebecca GP IEEE TI Design, Implementation and Evaluation of a Game-Based Intervention Targeting Latino Children for Improving Obesity Outcomes SO 2016 IEEE INTERNATIONAL CONFERENCE ON SERIOUS GAMES AND APPLICATIONS FOR HEALTH SE IEEE International Conference on Serious Games and Applications for Health LA English DT Proceedings Paper CT IEEE International Conference on Serious Games and Applications for Health CY MAY 11-13, 2016 CL Orlando, FL SP UCF, Univ Central Florida, Florida Interact Entertainment Acad, Inst Politecnico Cavado Ave, Escola Superior Tecnologia, IEEE, IEEE Comp Soc DE Serious games; health intervention; behavior change; obesity ID PHYSICAL-ACTIVITY; UNITED-STATES; HEALTH; ADOLESCENTS; BEHAVIOR AB This paper presents the design, implementation and evaluation of a hybrid clinic plus home based intervention targeting Latino children to improve obesity outcomes. The intervention applies motivational game based learning and behavior change theories during design. Latino American children are the main target group for this study as they have significantly high obesity rates due to socio-economic conditions and lack of awareness. There have been several interventions that have targeted game based strategies in the clinic to promote health outcomes and some have even targeted obesity problems, however to our knowledge this is the first effort that adds an in-home component to the clinical intervention. We discuss in detail the challenges faced while designing and implementing this hybrid clinical trial. Finally, we present the evaluation results from a randomized clinical trial that recruited 101 children. C1 [Amresh, Ashish] Arizona State Univ, Ira A Fulton Sch Engn, Mesa, AZ 85212 USA. [Sinha, Madhumita] Natl Inst Hlth, Phoenix, AZ USA. [Salla, Rahul] Arizona State Univ, Decis Theater, Tempe, AZ USA. [Birr, Rebecca] Maricopa Integrated Hlth Syst, Phoenix, AZ USA. RP Amresh, A (reprint author), Arizona State Univ, Ira A Fulton Sch Engn, Mesa, AZ 85212 USA. EM amresh@asu.edu; madhumita.sinha@nih.gov; Rahul.Salla@asu.edu; Rebecca.birr@mihs.org NR 20 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2330-5649 BN 978-1-5090-2209-0 J9 IEEE INT CONF SERIOU PY 2016 PG 8 WC Computer Science, Information Systems; Engineering, Electrical & Electronic; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA BG0YN UT WOS:000386581100036 ER PT J AU Rebholz, CM Tin, A Liu, Y Kuczmarski, MF Evans, MK Zonderman, AB Crews, DC AF Rebholz, Casey M. Tin, Adrienne Liu, Yang Kuczmarski, Marie Fanelli Evans, Michele K. Zonderman, Alan B. Crews, Deidra C. TI Dietary Magnesium and Kidney Function Decline: The Healthy Aging in Neighborhoods of Diversity across the Life Span Study SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Diet; Glomerular filtration rate; Healthy Aging in Neighborhoods of Diversity across the Life Span; Kidney disease; Magnesium; Primary prevention ID BLOOD-PRESSURE; ACID LOAD; UNITED-STATES; STOP HYPERTENSION; SERUM MAGNESIUM; DASH DIET; DISEASE; RISK; ADULTS; HYPOMAGNESEMIA AB Background: Prior studies suggest that certain aspects of the diet related to magnesium intake, such as dietary acid load, protein intake and dietary patterns rich in fruits and vegetables, may impact kidney disease risk. We hypothesized that lower dietary magnesium intake would be prospectively associated with more rapid kidney function decline. Methods: Among participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study with estimated glomerular filtration rate (eGFR) >= 60 ml/min/1.73 m(2) at baseline (2004-2009), dietary magnesium intake was calculated from two 24-hour dietary recalls. Rapid decline was defined as >= 3% eGFR decline per year. Results: Median (25th-75th percentile) dietary magnesium intake was 116 (96-356) mg/1,000 kcal. Among 1,252 participants, those with lower dietary magnesium intake were younger, and were more likely to be African-American men. A total of 177 participants (14.1%) experienced rapid eGFR decline over a median follow-up of 5 years. Lower dietary magnesium intake was significantly associated with a greater odds of rapid eGFR decline (OR for tertile 1 vs. 3: 2.02, 95% CI 1.05-3.86, p value for trend across tertiles = 0.02) in analyses adjusted for sociodemographics (age, sex, race, education level, health insurance status, poverty status), kidney disease risk factors (smoking status, diabetes, hemoglobin A1c, hypertension, body mass index), baseline eGFR and dietary factors (total energy intake; diet quality; dietary intake of fiber, sodium, calcium, potassium and phosphorus). Conclusions: In this urban population, lower dietary magnesium intake was independently associated with greater odds of rapid kidney function decline. (C) 2016 S. Karger AG, Basel C1 [Rebholz, Casey M.; Tin, Adrienne] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 2024 East Monument St,Suite 2-600, Baltimore, MD 21287 USA. [Rebholz, Casey M.; Tin, Adrienne; Crews, Deidra C.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21218 USA. [Liu, Yang; Crews, Deidra C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21218 USA. [Evans, Michele K.; Zonderman, Alan B.] NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA. [Kuczmarski, Marie Fanelli] Univ Delaware, Dept Behav Hlth & Nutr, Coll Hlth Sci, Newark, DE USA. RP Rebholz, CM (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 2024 East Monument St,Suite 2-600, Baltimore, MD 21287 USA. EM crebhol1@jhu.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural Research Program of the National Institute on Aging, National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK097184, K01 DK10778] FX This research was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. Dr. Deidra C. Crews is supported by grant K23 DK097184 from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Casey M. Rebholz is supported by grant K01 DK107782 from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 51 TC 2 Z9 2 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2016 VL 44 IS 5 BP 381 EP 387 DI 10.1159/000450861 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA EA8LF UT WOS:000386885600007 PM 27771720 ER PT J AU Okui, S Meguro, A Takeuchi, M Yamane, T Okada, E Iijima, Y Mizuki, N AF Okui, Shintaro Meguro, Akira Takeuchi, Masaki Yamane, Takahiro Okada, Eiichi Iijima, Yasuhito Mizuki, Nobuhisa TI Analysis of the association between the LUM rs3759223 variant and high myopia in a Japanese population SO CLINICAL OPHTHALMOLOGY LA English DT Article DE high myopia; lumican; association study; polymorphism ID GENOME-WIDE ASSOCIATION; LUMICAN GENE; REFRACTIVE ERROR; CONTINUITY CORRECTION; EDUCATION INFLUENCES; POLYMORPHISMS; METAANALYSIS; SUSCEPTIBILITY; IDENTIFICATION; EPIDEMIOLOGY AB Purpose: Many studies have investigated the relationship of the lumican gene (LUM) rs3759223 variant with the risk of high myopia, but the results have been inconsistent and inconclusive. In this study, we investigated whether LUM rs3759223 is associated with high myopia in a Japanese population. Methods: We recruited 1,585 Japanese patients with high myopia (spherical equivalent [SE] <-9.00 diopters [D]) and 1,011 Japanese healthy controls (SE >= -1.00 D). The rs3759223 variant was genotyped using the TaqMan assay, and the allelic and genotypic diversity among cases and controls was analyzed according to the SE level. Results: In the allelic tests, the odds ratio (OR) for the T allele of rs3759223 tended to increase with the progression of SE, and the highest OR (1.56) was found in patients with SE <-15 D in both eyes. The OR of the T allele tended to increase with the progression of SE in the additive, dominant, and recessive inheritance models. However, we found no significant associations for any of the alleles or genotype models. Conclusion: These data support the possibility that the LUM rs3759223 T allele accelerates the progression of SE in the Japanese population, although no significant associations were observed in this study. Additional genetic studies with larger samples that take into account the degree of SE are needed to clarify the contribution of rs3759223 to the risk of high myopia. C1 [Okui, Shintaro; Meguro, Akira; Takeuchi, Masaki; Yamane, Takahiro; Mizuki, Nobuhisa] Yokohama City Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med, Yokohama, Kanagawa, Japan. [Takeuchi, Masaki] NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. [Okada, Eiichi] Okada Eye Clin, Yokohama, Kanagawa, Japan. [Iijima, Yasuhito] Aoto Eye Clin, Yokohama, Kanagawa, Japan. RP Meguro, A (reprint author), Yokohama City Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. EM akmeguro@yokohama-cu.ac.jp NR 29 TC 0 Z9 0 U1 2 U2 2 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-5483 J9 CLIN OPHTHALMOL JI Clin. Ophthalmol. PY 2016 VL 10 BP 2157 EP 2163 DI 10.2147/OPTH.S104761 PG 7 WC Ophthalmology SC Ophthalmology GA EA3UB UT WOS:000386529600001 PM 27826181 ER PT J AU Racine, AM Clark, LR Berman, SE Koscik, RL Mueller, KD Norton, D Nicholas, CR Blennow, K Zetterberg, H Jedynak, B Bilgel, M Carlsson, CM Christian, BT Asthana, S Johnson, SC AF Racine, Annie M. Clark, Lindsay R. Berman, Sara E. Koscik, Rebecca L. Mueller, Kimberly D. Norton, Derek Nicholas, Christopher R. Blennow, Kaj Zetterberg, Henrik Jedynak, Bruno Bilgel, Murat Carlsson, Cynthia M. Christian, Bradley T. Asthana, Sanjay Johnson, Sterling C. TI Associations between Performance on an Abbreviated CogState Battery, Other Measures of Cognitive Function, and Biomarkers in People at Risk for Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Amyloid; biomarkers; cerebrospinal fluid; cognitive impairment; CogState; computerized cognitive testing; neural injury; preclinical Alzheimer's disease ID MIDDLE-AGED ADULTS; AMYLOID-BETA; OLDER-ADULTS; MEMORY DECLINE; DIAGNOSTIC GUIDELINES; COMPUTERIZED BATTERY; WISCONSIN-REGISTRY; NATIONAL INSTITUTE; SCREENING-TEST; A-BETA AB It is not known whether computerized cognitive assessments, like the CogState battery, are sensitive to preclinical cognitive changes or pathology in people at risk for Alzheimer's disease (AD). In 469 late middle-aged participants from the Wisconsin Registry for Alzheimer's Prevention (mean age 63.8 +/- 7 years at testing; 67% female; 39% APOE4+), we examined relationships between a CogState abbreviated battery (CAB) of seven tests and demographic characteristics, traditional paper-based neuropsychological tests as well as a composite cognitive impairment index, cognitive impairment status (determined by consensus review), and biomarkers for amyloid and tau (CSF phosphorylated-tau/A beta(42) and global PET-PiB burden) and neural injury (CSF neurofilament light protein). CSF and PET-PiB were collected in n = 71 and n = 91 participants, respectively, approximately four years prior to CAB testing. For comparison, we examined three traditional tests of delayed memory in parallel. Similar to studies in older samples, the CAB was less influenced by demographic factors than traditional tests. CAB tests were generally correlated with most paper-based cognitive tests examined and mapped onto the same cognitive domains. Greater composite cognitive impairment index was associated with worse performance on all CAB tests. Cognitively impaired participants performed significantly worse compared to normal controls on all but one CAB test. Poorer One Card Learning test performance was associated with higher levels of CSF phosphorylated-tau/A beta(42). These results support the use of the CogState battery as measures of early cognitive impairment in studies of people at risk for AD. C1 [Clark, Lindsay R.; Nicholas, Christopher R.; Carlsson, Cynthia M.; Asthana, Sanjay; Johnson, Sterling C.] Wm S Middleton Vet Hosp, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Clark, Lindsay R.; Koscik, Rebecca L.; Mueller, Kimberly D.; Carlsson, Cynthia M.; Johnson, Sterling C.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI USA. [Racine, Annie M.; Clark, Lindsay R.; Berman, Sara E.; Nicholas, Christopher R.; Carlsson, Cynthia M.; Asthana, Sanjay; Johnson, Sterling C.] Univ Wisconsin, Sch Med & Publ Hlth, Alzheimers Dis Res Ctr, Madison, WI USA. [Racine, Annie M.] Univ Wisconsin, Inst Aging, Madison, WI USA. [Racine, Annie M.; Johnson, Sterling C.] Univ Wisconsin, Neurosci & Publ Policy Program, Madison, WI USA. Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Christian, Bradley T.; Johnson, Sterling C.] Univ Wisconsin, Waisman Lab Brain Imaging & Behav, Madison, WI USA. [Blennow, Kaj; Zetterberg, Henrik] Univ Gothenburg, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Sahlgrenska Acad, Molndal, Sweden. [Blennow, Kaj; Zetterberg, Henrik] Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden. [Zetterberg, Henrik] UCL, Inst Neurol, London, England. [Jedynak, Bruno] Portland State Univ, Dept Math & Stat, Portland, OR 97207 USA. [Christian, Bradley T.] Univ Wisconsin, Dept Med Phys, Sch Med & Publ Hlth, 1530 Med Sci Ctr, Madison, WI 53706 USA. [Bilgel, Murat] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. [Bilgel, Murat] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA. [Norton, Derek] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. RP Johnson, SC (reprint author), William S Middleton Mem VA Hosp, GRECC, 2500 Overlook Terrace 11G, Madison, WI 53705 USA. EM scj@medicine.wisc.edu FU National Institutes of Health [AG021155, AG027161, AG000213, P50 AG033514, AG037639, P30 HD003352]; Clinical and Translational Science Award [UL1RR025011]; Neuroscience & Public Policy Program [SES-0849122]; Neuroscience Training Program [T32GM007507]; Medical Scientist Training Program [T32GM008692]; Wisconsin Alzheimer's Institute Lou Holland Fund; Swedish Research Council; Swedish Brain Foundation; Knut and Alice Wallenberg Foundation; Torsten Soderberg's Foundation; Veterans Administration; Intramural Research Program of the National Institute on Aging, National Institutes of Health; Michael J. Fox Foundation, MJFF Research Grant [9310] FX This research was supported by the National Institutes of Health (SCJ, AG021155, AG027161), (SA, AG000213, P50 AG033514), and (BBB, AG037639); by P30 HD003352; by a Clinical and Translational Science Award (UL1RR025011) to the University of Wisconsin, Madison; by the Neuroscience & Public Policy Program (RK, SES-0849122); by the Neuroscience Training Program (MH, T32GM007507); by the Medical Scientist Training Program (T32GM008692); by the Wisconsin Alzheimer's Institute Lou Holland Fund; and by the Swedish Research Council, the Swedish Brain Foundation, the Knut and Alice Wallenberg Foundation, and Torsten Soderberg's Foundation to the University of Gothenburg. Portions of this research were supported by the Veterans Administration including facilities and resources at the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital, Madison, WI; by the Intramural Research Program of the National Institute on Aging, National Institutes of Health; and by the Michael J. Fox Foundation for Parkinson's Research, MJFF Research Grant ID: 9310. NR 57 TC 0 Z9 0 U1 2 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2016 VL 54 IS 4 BP 1395 EP 1408 DI 10.3233/JAD-160528 PG 14 WC Neurosciences SC Neurosciences & Neurology GA EA6PA UT WOS:000386749900015 PM 27589532 ER PT J AU Xie, YX Zhang, JW He, YG Cheng, AB Yin, QN AF Xie, Yuxi Zhang, Junwei He, Yonggui Cheng, Aibin Yin, Qinan TI Study on FOA_BP remote sepsis diagnosis based on wireless sensor network SO JOURNAL OF INTELLIGENT & FUZZY SYSTEMS LA English DT Article DE Wireless sensor network; ZigBee network; fruit fly algorithm; BP neural network; sepsis diagnosis ID MODEL AB With the development of economic level and growth in the living standard, how to enhance the accuracy and efficiency of remote sepsis diagnosis has become the key issue and hot topic in the current medical research. As the traditional BP neural network is poor in the generalization ability and needs a large number of samples, we proposed the study on remote sepsis diagnosis by using the FOA-optimized BP neural network. Besides, based on the wireless sensor network and ZigBee network, we constructed the mathematical model of FOA_BP remote sepsis diagnosis based on wireless sensor network. The sepsis data set of School of Medicine and Public Health, University of Wisconsin was used as the object of study. The FOA-BP algorithm is significantly superior to the BP neural network algorithm in the diagnosis accuracy, verifying the validity and reliability of making a sepsis diagnosis with FOA_BP. Therefore, the method can be popularized to other fields to solve other similar problems. C1 [Xie, Yuxi; Zhang, Junwei; He, Yonggui; Cheng, Aibin] North China Coal Med Coll Undergrad, Tangshan 063000, Peoples R China. [Yin, Qinan] NIH, Bldg 10, Bethesda, MD 20892 USA. RP Zhang, JW (reprint author), North China Coal Med Coll Undergrad, Tangshan 063000, Peoples R China. EM zhangjunweincust@163.com NR 19 TC 0 Z9 0 U1 3 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1064-1246 EI 1875-8967 J9 J INTELL FUZZY SYST JI J. Intell. Fuzzy Syst. PY 2016 VL 31 IS 5 BP 2737 EP 2743 DI 10.3233/JIFS-169113 PG 7 WC Computer Science, Artificial Intelligence SC Computer Science GA EA3UY UT WOS:000386532000028 ER PT J AU Sengupta, A Ghosh, S Das, BK Panda, A Tripathy, R Pied, S Ravindran, B Pathak, S Sharma, S Sonawat, HM AF Sengupta, Arjun Ghosh, Soumita Das, Bidyut K. Panda, Abhinash Tripathy, Rina Pied, Sylviane Ravindran, B. Pathak, Sulabha Sharma, Shobhona Sonawat, Haripalsingh M. TI Host metabolic responses to Plasmodium falciparum infections evaluated by H-1 NMR metabolomics SO MOLECULAR BIOSYSTEMS LA English DT Article ID HUMAN CEREBROSPINAL-FLUID; CEREBRAL MALARIA; NMR-SPECTROSCOPY; SERUM; PLASMA; CHILDREN; ANTIGENS; LIPIDS; SHOCK AB The human malarial parasite Plasmodium falciparum causes the most severe forms of malarial infections, which include cerebral malaria and various organ dysfunctions amongst adults in India. So far no dependable clinical descriptor is available that can distinguish cerebral malaria from other symptomatically similar diseases such as sepsis and encephalitis. This study aims at evaluating the differential metabolic features of plasma samples from P. falciparum patients with varying severities, and patients suffering from symptomatically similar diseases. H-1 Nuclear Magnetic Resonance (NMR) based metabolic profiling of the plasma of the infected individuals and the control population was performed. The differences in the plasma profiles were evaluated through multivariate statistical analyses. The results suggest malaria-specific elevation of plasma lipoproteins. Such an increase was absent in control populations. In addition, cerebral malaria patients exhibited a decrease in plasma glycoproteins; such a reduction was not observed in malarial patients without cerebral symptoms. The data presented here indicates that the metabolism and/or transport of the plasma lipids is specifically perturbed by malarial infections. The differential perturbation of the plasma glycoprotein levels in cerebral malaria patients may have important implications in the diagnosis of cerebral malaria. C1 [Sengupta, Arjun] Univ Penn, Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA. [Ghosh, Soumita; Sharma, Shobhona; Sonawat, Haripalsingh M.] Tata Inst Fundamental Res, Dept Chem Sci, Homi Bhabha Rd, Bombay, Maharashtra, India. [Das, Bidyut K.; Panda, Abhinash] SCB Med Coll, Dept Med, Cuttack, Odhisa, India. [Tripathy, Rina] SCB Med Coll, Dept Biochem, Cuttack, Odhisa, India. [Pied, Sylviane] Ctr Infect & Immun Lille, Lille, France. [Ravindran, B.] Inst Life Sci, Bhubaneswar 751023, Odisha, India. [Pathak, Sulabha] TIFR, Dept Biol Sci, Bombay, Maharashtra, India. [Ghosh, Soumita] NIA, 251 Bayview Blvd, Baltimore, MD 21224 USA. RP Sharma, S; Sonawat, HM (reprint author), Tata Inst Fundamental Res, Dept Chem Sci, Homi Bhabha Rd, Bombay, Maharashtra, India. EM harisonawat@gmail.com FU CSIR, Government of India; Indo-French Centre for the Promotion of Advance Research (IFCPAR) [IFC/3703-2] FX The authors thank the staff of the National Facility for High Field NMR in TIFR for their help during NMR experiments. AS acknowledges CSIR, Government of India for the SPM Fellowship. This work was partially supported by Indo-French Centre for the Promotion of Advance Research (IFCPAR) [Grant number: IFC/3703-2]. NR 31 TC 2 Z9 2 U1 2 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X EI 1742-2051 J9 MOL BIOSYST JI Mol. Biosyst. PY 2016 VL 12 IS 11 BP 3324 EP 3332 DI 10.1039/c6mb00362a PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EA5OC UT WOS:000386669400009 PM 27546486 ER PT J AU Drgonova, J Walther, D Hartstein, GL Bukhari, MO Baumann, MH Katz, J Hall, FS Arnold, ER Flax, S Riley, A Rivero, O Lesch, KP Troncoso, J Ranscht, B Uhl, GR AF Drgonova, Jana Walther, Donna Hartstein, G. Luke Bukhari, Mohammad O. Baumann, Michael H. Katz, Jonathan Hall, F. Scott Arnold, Elizabeth R. Flax, Shaun Riley, Anthony Rivero, Olga Lesch, Klaus-Peter Troncoso, Juan Ranscht, Barbara Uhl, George R. TI Cadherin 13: Human cis-Regulation and Selectively Altered Addiction Phenotypes and Cerebral Cortical Dopamine in Knockout Mice SO MOLECULAR MEDICINE LA English DT Article ID GENOME-WIDE ASSOCIATION; SMOKING-CESSATION SUCCESS; T-CADHERIN; MOLECULAR-GENETICS; CELL-ADHESION; NICOTINE REPLACEMENT; ALCOHOL DEPENDENCE; BRAIN; DISORDERS; RAT AB The cadherin 13 (CDH13) gene encodes a cell adhesion molecule likely to influence development and connections of brain circuits that modulate addiction, locomotion and cognition, including those that involve midbrain dopamine neurons. Human CDH13 mRNA expression differs by more than 80% in postmortem cerebral cortical samples from individuals with different CDH13 genotypes, supporting examination of mice with altered CDH13 expression as models for common human variation at this locus. Constitutive CDH13 knockout mice display evidence for changed cocaine reward: shifted dose response relationship in tests of cocaine-conditioned place preference using doses that do not alter cocaine-conditioned taste aversion. Reduced adult CDH13 expression in conditional knockouts also alters cocaine reward in ways that correlate with individual differences in cortical CDH13 mRNA levels. In control and comparison behavioral assessments, knockout mice display modestly quicker acquisition of rotarod and water maze tasks, with a trend toward faster acquisition of 5-choice serial reaction time tasks that otherwise displayed no genotype-related differences. They display significant differences in locomotion in some settings, with larger effects in males. In assessments of brain changes that might contribute to these behavioral differences, there are selective alterations of dopamine levels, dopamine/metabolite ratios, dopaminergic fiber densities and mRNA encoding the activity dependent transcription factor npas4 in cerebral cortex of knockout mice. These novel data and previously reported human associations of CDH13 variants with addiction, individual differences in responses to stimulant administration and attention deficit hyperactivity disorder (ADHD) phenotypes suggest that levels of CDH13 expression, through mechanisms likely to include effects on mesocortical dopamine, influence stimulant reward and may contribute modestly to cognitive and locomotor phenotypes relevant to ADHD. Online address: http://www.molmed.org C1 [Drgonova, Jana; Walther, Donna; Hartstein, G. Luke; Hall, F. Scott; Arnold, Elizabeth R.; Uhl, George R.] NIDA, Mol Neurobiol, Intramural Res Program, Baltimore, MD USA. [Bukhari, Mohammad O.; Baumann, Michael H.; Katz, Jonathan] NIDA, Med Chem, Intramural Res Program, Baltimore, MD USA. [Flax, Shaun; Riley, Anthony] Amer Univ, Dept Psychol, Washington, DC 20016 USA. [Rivero, Olga; Lesch, Klaus-Peter] Univ Wurzburg, Dept Psychiat, Translat Neurobiol, Wurzburg, Germany. [Troncoso, Juan] Johns Hopkins Sch Med, Div Neuropathol, Baltimore, MD USA. [Ranscht, Barbara] Sanford Burnham Med Res Inst, La Jolla, CA USA. [Uhl, George R.] New Mexico VA Healthcare Syst, Res, Bldg 66,Room 127,1501 San Pedro SE, Albuquerque, NM 87111 USA. RP Uhl, GR (reprint author), New Mexico VA Healthcare Syst, Res, Bldg 66,Room 127,1501 San Pedro SE, Albuquerque, NM 87111 USA. EM George.Uhl@va.gov RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X FU National Institutes of Health (NIH)-Intramural Research Program; NIDA; DHHS; Biomedical Research Institute of New Mexico; NIH [HL102680]; European Community (EC: AGGRESSOTYPE FP7) [602805]; DFG [SFB TRR 58/A5]; Fritz Thyssen Foundation [Az.10.13.1185] FX This work was supported by the National Institutes of Health (NIH)-Intramural Research Program, NIDA, DHHS and the Biomedical Research Institute of New Mexico (G Uhl), NIH grant HL102680 (B Ranscht), the European Community (EC: AGGRESSOTYPE FP7/No. 602805 (OR and KPL), the DFG (SFB TRR 58/A5 OR and KPL) and the Fritz Thyssen Foundation (Az.10.13.1185 OR and KPL). NR 55 TC 2 Z9 2 U1 2 U2 2 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 EI 1528-3658 J9 MOL MED JI Mol. Med. PY 2016 VL 22 BP 537 EP 547 DI 10.2119/molmed.2015.00170 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA EA4HV UT WOS:000386573000001 ER PT J AU Muralidharan, P Hayes, D Black, SM Mansour, HM AF Muralidharan, Priya Hayes, Don, Jr. Black, Stephen M. Mansour, Heidi M. TI Microparticulate/nanoparticulate powders of a novel Nrf2 activator and an aerosol performance enhancer for pulmonary delivery targeting the lung Nrf2/Keap-1 pathway SO MOLECULAR SYSTEMS DESIGN & ENGINEERING LA English DT Article ID PHYSICOCHEMICAL CHARACTERIZATION; DISPERSION PERFORMANCE; DIMETHYL FUMARATE; ENDOTHELIAL-CELLS; DIPALMITOYLPHOSPHATIDYLCHOLINE DPPC; MULTIFUNCTIONAL PARTICLES; RESPIRATORY DELIVERY; INHALATION DELIVERY; NITRIC-OXIDE; BLOOD-FLOW AB This systematic and comprehensive study reports for the first time on the successful rational design of advanced inhalable therapeutic dry powders containing dimethyl fumarate, a first-in-class Nrf2 activator drug to treat pulmonary inflammation, using particle engineering design technology for targeted delivery to the lungs as advanced spray dried (SD) one-component DPIs. In addition, two-component co-spray dried (co-SD) DMF : D-Man DPIs with high drug loading were successfully designed for targeted lung delivery as advanced DPIs using organic solution advanced spray drying in closed mode. Regional targeted deposition using design of experiments (DoE) for in vitro predictive lung modeling based on aerodynamic properties was tailored based on composition and spray drying parameters. These findings indicate the significant potential of using D-Man in spray drying to improve particle formation and aerosol performance of small molecule with a relatively low melting point. These respirable microparticles/nanoparticles in the solid-state exhibited excellent aerosol dispersion performance with an FDA-approved human DPI device. Using in vitro predictive lung deposition modeling, the aerosol deposition patterns of these particles show the capability to reach lower airways to treat inflammation in this region in pulmonary diseases such as acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), and pulmonary endothelial disease. C1 [Muralidharan, Priya; Mansour, Heidi M.] Univ Arizona, Coll Pharm, Skaggs Pharmaceut Sci Ctr, 1703 E Mabel St, Tucson, AZ 85721 USA. [Hayes, Don, Jr.] Ohio State Univ, Coll Med, Lung Transplant Program, Dept Pediat, Columbus, OH 43205 USA. [Hayes, Don, Jr.] Ohio State Univ, Coll Med, Lung Transplant Program, Dept Internal Med, Columbus, OH 43205 USA. [Hayes, Don, Jr.] Ohio State Univ, Coll Med, Heart Lung Transplant Program, Dept Pediat, Columbus, OH 43205 USA. [Hayes, Don, Jr.] Ohio State Univ, Coll Med, Heart Lung Transplant Program, Dept Internal Med, Columbus, OH 43205 USA. [Hayes, Don, Jr.] Ohio State Univ, Coll Med, Davis Heart & Lung Res Inst, Columbus, OH 43205 USA. [Black, Stephen M.] Univ Arizona, Div Translat & Regenerat Med, Dept Med, Tucson, AZ 85724 USA. [Mansour, Heidi M.] Univ Arizona, Inst Environm, Tucson, AZ 85721 USA. [Mansour, Heidi M.] Univ Arizona, Ctr Comprehens Canc, Natl Canc Inst, Tucson, AZ 85721 USA. [Mansour, Heidi M.] Univ Arizona, Res Inst BIO5, Tucson, AZ 85721 USA. RP Mansour, HM (reprint author), Univ Arizona, Coll Pharm, Skaggs Pharmaceut Sci Ctr, 1703 E Mabel St, Tucson, AZ 85721 USA.; Mansour, HM (reprint author), Univ Arizona, Inst Environm, Tucson, AZ 85721 USA.; Mansour, HM (reprint author), Univ Arizona, Ctr Comprehens Canc, Natl Canc Inst, Tucson, AZ 85721 USA.; Mansour, HM (reprint author), Univ Arizona, Res Inst BIO5, Tucson, AZ 85721 USA. EM mansour@pharmacy.arizona.edu FU NHLBI NIH HHS [R01 HL060190]; NICHD NIH HHS [R01 HD039110] NR 58 TC 2 Z9 2 U1 4 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2058-9689 J9 MOL SYST DES ENG JI Mol. Syst. Des. Eng. PY 2016 VL 1 IS 1 BP 48 EP 65 DI 10.1039/c5me00004a PG 18 WC Engineering, Chemical SC Engineering GA EA4YE UT WOS:000386622100005 PM 27774309 ER PT J AU Saparov, A Ogay, V Nurgozhin, T Jumabay, M Chen, WCW AF Saparov, Arman Ogay, Vyacheslav Nurgozhin, Talgat Jumabay, Medet Chen, William C. W. TI Preconditioning of Human Mesenchymal Stem Cells to Enhance Their Regulation of the Immune Response SO STEM CELLS INTERNATIONAL LA English DT Review ID STROMAL CELLS; INTERFERON-GAMMA; T-CELLS; IMMUNOMODULATORY PROPERTIES; STEM/STROMAL CELLS; EFFECTOR FUNCTION; INDUCED COLITIS; IN-VIVO; SPHEROIDS; SURVIVAL AB Mesenchymal stem cells (MSCs) have attracted the attention of researchers and clinicians for their ability to differentiate into a number of cell types, participate in tissue regeneration, and repair the damaged tissues by producing various growth factors and cytokines, as well as their unique immunoprivilege in alloreactive hosts. The immunomodulatory functions of exogenous MSCs have been widely investigated in immune-mediated inflammatory diseases and transplantation research. However, a harsh environment at the site of tissue injury/inflammation with insufficient oxygen supply, abundance of reactive oxygen species, and presence of other harmful molecules that damage the adoptively transferred cells collectively lead to low survival and engraftment of the transferred cells. Preconditioning of MSCs ex vivo by hypoxia, inflammatory stimulus, or other factors/conditions prior to their use in therapy is an adaptive strategy that prepares MSCs to survive in the harsh environment and to enhance their regulatory function of the local immune responses. This review focuses on a number of approaches in preconditioning human MSCs with the goal of augmenting their capacity to regulate both innate and adaptive immune responses. C1 [Saparov, Arman] Nazarbayev Univ, Dept Biomed Sci, Sch Med, Astana 010000, Kazakhstan. [Ogay, Vyacheslav] Natl Biotechnol Ctr, Stem Cell Lab, Astana 010000, Kazakhstan. [Nurgozhin, Talgat] Nazarbayev Univ, Ctr Life Sci, Astana 010000, Kazakhstan. [Jumabay, Medet] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, Los Angeles, CA 90095 USA. [Chen, William C. W.] MIT, Res Lab Elect, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Chen, William C. W.] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RP Saparov, A (reprint author), Nazarbayev Univ, Dept Biomed Sci, Sch Med, Astana 010000, Kazakhstan. EM asaparov@nu.edu.kz FU Nazarbayev University FX This work was supported by a grant from Nazarbayev University (Arman Saparov). NR 71 TC 0 Z9 0 U1 3 U2 3 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 1687-966X EI 1687-9678 J9 STEM CELLS INT JI Stem Cells Int. PY 2016 AR 3924858 DI 10.1155/2016/3924858 PG 10 WC Cell & Tissue Engineering SC Cell Biology GA EA7WB UT WOS:000386842000001 ER PT B AU Xu, YY Tokar, EJ Waalkes, MP AF Xu, Yuanyuan Tokar, Erik J. Waalkes, Michael P. BE States, JC TI STEM CELL TARGETING AND ALTERATION BY ARSENIC SO ARSENIC: EXPOSURE SOURCES, HEALTH RISKS, AND MECHANISMS OF TOXICITY LA English DT Article; Book Chapter ID ACUTE MYELOID-LEUKEMIA; EPITHELIAL-MESENCHYMAL TRANSITION; ACUTE PROMYELOCYTIC LEUKEMIA; INITIATING CELLS; MALIGNANT-TRANSFORMATION; CANCER-MORTALITY; HEDGEHOG PATHWAY; PROSTATE-CANCER; APOPTOTIC DEATH; DRINKING-WATER C1 [Xu, Yuanyuan; Tokar, Erik J.; Waalkes, Michael P.] NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program Lab, POB 12233, Res Triangle Pk, NC 27709 USA. RP Xu, YY (reprint author), NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 108 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA BN 978-1-118-87659-6; 978-1-118-51114-5 PY 2016 BP 397 EP 420 PG 24 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA BG0IF UT WOS:000386249000018 ER PT B AU Tokar, EJ Xu, YY Waalkes, MP AF Tokar, Erik J. Xu, Yuanyuan Waalkes, Michael P. BE States, JC TI CANCER INDUCED BY EXPOSURE TO ARSENICALS IN ANIMALS SO ARSENIC: EXPOSURE SOURCES, HEALTH RISKS, AND MECHANISMS OF TOXICITY LA English DT Article; Book Chapter ID MALE F344 RATS; DIMETHYLARSINIC ACID; CD1 MICE; IN-UTERO; URINARY-BLADDER; POSTNATAL DIETHYLSTILBESTROL; DRINKING-WATER; ADRENAL-TUMORS; LUNG-CANCER; DNA-DAMAGE C1 [Tokar, Erik J.; Xu, Yuanyuan; Waalkes, Michael P.] NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program Lab, POB 12233, Res Triangle Pk, NC 27709 USA. RP Tokar, EJ (reprint author), NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 43 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA BN 978-1-118-87659-6; 978-1-118-51114-5 PY 2016 BP 441 EP 452 PG 12 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA BG0IF UT WOS:000386249000020 ER PT J AU Kane, AE Hilmer, SN Mach, J Mitchell, SJ de Cabo, R Howlett, SE AF Kane, Alice E. Hilmer, Sarah N. Mach, John Mitchell, Sarah J. de Cabo, Rafael Howlett, Susan E. TI Animal models of frailty: current applications in clinical research SO CLINICAL INTERVENTIONS IN AGING LA English DT Review DE mouse models; frailty index; frailty phenotype; IL-10 knock-out ID NURSING-HOME RESIDENTS; SKELETAL-MUSCLE; OLDER-ADULTS; EXERCISE INTERVENTIONS; DIETARY RESTRICTION; ELDERLY-PEOPLE; SERUM-ALBUMIN; MOUSE MODEL; AGING MICE; LIFE-SPAN AB The ethical, logistical, and biological complications of working with an older population of people inherently limits clinical studies of frailty. The recent development of animal models of frailty, and tools for assessing frailty in animal models provides an invaluable opportunity for frailty research. This review summarizes currently published animal models of frailty including the interleukin-10 knock-out mouse, the mouse frailty phenotype assessment tool, and the mouse clinical frailty index. It discusses both current and potential roles of these models in research into mechanisms of frailty, interventions to prevent/delay frailty, and the effect of frailty on outcomes. Finally, this review discusses some of the challenges and opportunities of translating research findings from animals to humans. C1 [Kane, Alice E.; Howlett, Susan E.] Dalhousie Univ, Dept Pharmacol, Halifax, NS, Canada. [Hilmer, Sarah N.; Mach, John] Univ Sydney, Kolling Inst Med Res, Sydney, NSW, Australia. [Hilmer, Sarah N.; Mach, John] Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia. [Hilmer, Sarah N.; Mach, John] Royal North Shore Hosp, Dept Clin Pharmacol, Sydney, NSW, Australia. [Hilmer, Sarah N.; Mach, John] Royal North Shore Hosp, Dept Aged Care, Sydney, NSW, Australia. [Mitchell, Sarah J.; de Cabo, Rafael] NIA, NIH, Baltimore, MD 21224 USA. RP Kane, AE (reprint author), Dept Pharmacol, Level 5,Sir Charles Tupper Med Bldg,POB 15000, Halifax, NS B3H 4R2, Canada. EM alice.kane@dal.ca OI , rafael/0000-0003-2830-5693 FU intramural research program of the National Institute on Aging; National Institutes of Health FX SJM and RdC are supported by the intramural research program of the National Institute on Aging, National Institutes of Health. The authors report no other conflicts of interest in this work. NR 63 TC 0 Z9 0 U1 4 U2 4 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-1998 J9 CLIN INTERV AGING JI Clin. Interv. Aging PY 2016 VL 11 BP 1519 EP 1529 DI 10.2147/CIA.S105714 PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA DZ9WY UT WOS:000386233100001 PM 27822024 ER PT S AU Shi, F Cheng, J Wang, L Yap, PT Shen, DG AF Shi, Feng Cheng, Jian Wang, Li Yap, Pew-Thian Shen, Dinggang BE Fuster, A Ghosh, A Kaden, E Rathi, Y Reisert, M TI Super-Resolution Reconstruction of Diffusion-Weighted Images Using 4D Low-Rank and Total Variation SO COMPUTATIONAL DIFFUSION MRI SE Mathematics and Visualization LA English DT Proceedings Paper CT MICCAI Workshop on Computational Diffusion MRI CY OCT09, 2015 CL Munich, GERMANY SP MICCAI ID HUMAN CONNECTOME PROJECT; CONNECTIVITY NETWORKS; MRI; IDENTIFICATION AB Diffusion-weighted imaging (DWI) provides invaluable information in white matter microstructure and is widely applied in neurological applications. However, DWI is largely limited by its relatively low spatial resolution. In this paper, we propose an image post-processing method, referred to as super-resolution reconstruction, to estimate a high spatial resolution DWI from the input low-resolution DWI, e.g., at a factor of 2. Instead of requiring specially designed DWI acquisition of multiple shifted or orthogonal scans, our method needs only a single DWI scan. To do that, we propose to model both the blurring and downsampling effects in the image degradation process where the low-resolution image is observed from the latent high-resolution image, and recover the latent high-resolution image with the help of two regularizations. The first regularization is four-dimensional (4D) low-rank, proposed to gather self-similarity information from both the spatial domain and the diffusion domain of 4D DWI. The second regularization is total variation, proposed to depress noise and preserve local structures such as edges in the image recovery process. Extensive experiments were performed on 20 subjects, and results show that the proposed method is able to recover the fine details of white matter structures, and outperform other approaches such as interpolation methods, non-local means based upsampling, and total variation based upsampling. C1 [Shi, Feng; Cheng, Jian; Wang, Li; Yap, Pew-Thian; Shen, Dinggang] Univ North Carolina Chapel Hill, Dept Radiol, Chapel Hill, NC 27514 USA. [Shi, Feng; Cheng, Jian; Wang, Li; Yap, Pew-Thian; Shen, Dinggang] Univ North Carolina Chapel Hill, BRIC, Chapel Hill, NC 27514 USA. [Cheng, Jian] NICHHD, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD 20892 USA. RP Shen, DG (reprint author), Univ North Carolina Chapel Hill, Dept Radiol, Chapel Hill, NC 27514 USA.; Shen, DG (reprint author), Univ North Carolina Chapel Hill, BRIC, Chapel Hill, NC 27514 USA. EM dgshen@med.unc.edu NR 21 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1612-3786 BN 978-3-319-28588-7; 978-3-319-28586-3 J9 MATH VIS PY 2016 BP 15 EP 25 DI 10.1007/978-3-319-28588-7_2 PG 11 WC Mathematical & Computational Biology; Mathematics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Mathematical & Computational Biology; Mathematics; Radiology, Nuclear Medicine & Medical Imaging GA BG0UZ UT WOS:000386535600002 ER PT J AU Pauchard, Y Fitze, T Browarnik, D Eskandari, A Pauchard, I Enns-Bray, W Palsson, H Sigurdsson, S Ferguson, SJ Harris, TB Gudnason, V Helgason, B AF Pauchard, Yves Fitze, Thomas Browarnik, Diego Eskandari, Amiraslan Pauchard, Irene Enns-Bray, William Palsson, Halldor Sigurdsson, Sigurdur Ferguson, Stephen J. Harris, Tamara B. Gudnason, Vilmundur Helgason, Benedikt TI Interactive graph-cut segmentation for fast creation of finite element models from clinical ct data for hip fracture prediction SO COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING LA English DT Article DE Hip fracture prediction; image segmentation; clinical computed tomography; image-based finite element modeling; femur segmentation ID PROXIMAL FEMORAL STRENGTH; BONE-MINERAL DENSITY; AUTOMATIC SEGMENTATION; IMAGE SEGMENTATION; FEMUR; WOMEN; MEN; ACCURATE; ASSOCIATION; REYKJAVIK AB In this study, we propose interactive graph cut image segmentation for fast creation of femur finite element (FE) models from clinical computed tomography scans for hip fracture prediction. Using a sample of N=48 bone scans representing normal, osteopenic and osteoporotic subjects, the proximal femur was segmented using manual (gold standard) and graph cut segmentation. Segmentations were subsequently used to generate FE models to calculate overall stiffness and peak force in a sideways fall simulations. Results show that, comparable FE results can be obtained with the graph cut method, with a reduction from 20 to 2-5min interaction time. Average differences between segmentation methods of 0.22mm were not significantly correlated with differences in FE derived stiffness (R-2=0.08, p=0.05) and weakly correlated to differences in FE derived peak force (R-2=0.16, p=0.01). We further found that changes in automatically assigned boundary conditions as a consequence of small segmentation differences were significantly correlated with FE derived results. The proposed interactive graph cut segmentation software MITK-GEM is freely available online at https://simtk.org/home/mitk-gem. C1 [Pauchard, Yves; Fitze, Thomas; Browarnik, Diego] Zurich Univ Appl Sci, Inst Appl Informat Technol, Winterthur, Switzerland. [Eskandari, Amiraslan; Enns-Bray, William; Ferguson, Stephen J.; Helgason, Benedikt] Swiss Fed Inst Technol, Inst Biomech, Zurich, Switzerland. [Eskandari, Amiraslan; Palsson, Halldor] Univ Iceland, Sch Engn & Nat Sci, Fac Ind Engn Mech Engn & Comp Sci, Reykjavik, Iceland. [Pauchard, Irene] Univ Calgary, McCaig Inst Bone & Joint Hlth, Cumming Sch Med, Calgary, AB, Canada. [Sigurdsson, Sigurdur; Gudnason, Vilmundur] Iceland Heart Assoc Res Inst, Kopavogur, Iceland. [Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20892 USA. [Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. RP Pauchard, Y (reprint author), Zurich Univ Appl Sci, Inst Appl Informat Technol, Winterthur, Switzerland. EM yves.pauchard@ucalgary.ca FU Intramural Research Program of the National Institute on Aging; National Eye Institute at the National Institutes of Health [NIH] [N01-AG-1-2100]; Icelandic Heart Association; Icelandic Parliament, St. Josef's Hospital Fund, Reykjavik, Iceland; School of Engineering Zurich University of Applied Sciences Winterthur FX This research was supported in part by the Intramural Research Program of the National Institute on Aging and National Eye Institute at the National Institutes of Health [NIH contract number N01-AG-1-2100], the Icelandic Heart Association, the Icelandic Parliament, St. Josef's Hospital Fund, Reykjavik, Iceland; the School of Engineering Zurich University of Applied Sciences Winterthur. NR 35 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1025-5842 EI 1476-8259 J9 COMPUT METHOD BIOMEC JI Comput. Methods Biomech. Biomed. Eng. PY 2016 VL 19 IS 16 BP 1693 EP 1703 DI 10.1080/10255842.2016.1181173 PG 11 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA EA1UV UT WOS:000386378400002 PM 27161828 ER PT J AU Gilleaudeau, GJ Frei, R Kaufman, AJ Kah, LC Azmy, K Bartley, JK Chernyavskiy, P Knoll, AH AF Gilleaudeau, G. J. Frei, R. Kaufman, A. J. Kah, L. C. Azmy, K. Bartley, J. K. Chernyavskiy, P. Knoll, A. H. TI Oxygenation of the mid-Proterozoic atmosphere: clues from chromium isotopes in carbonates SO GEOCHEMICAL PERSPECTIVES LETTERS LA English DT Article ID ANIMALS; SEAWATER; CHEMOSTRATIGRAPHY; VARIABILITY; ATLANTIC; OCEAN; BASIN; RISE AB Chromium (Cr) isotopes in marine sedimentary rocks can be used as a sensitive proxy for ancient atmospheric oxygen because Cr-isotope fractionation during terrestrial weathering only occurs when pO(2) exceeds a threshold value. This is a useful system when applied to rocks of mid-Proterozoic age, where fundamental questions persist about atmospheric pO(2) and its relationship to biological innovation. Whereas previous studies have focused on temporally limited iron-rich sedimentary rocks, we present new Cr-isotope data from a suite of mid-Proterozoic marine carbonate rocks. Application of the Cr-isotope proxy to carbonate rocks has the potential to greatly enhance the temporal resolution of Proterozoic palaeoredox data. Here we report positive delta Cr-53 values in four carbonate successions, extending the mid-Proterozoic record of Cr-isotope fractionation -and thus pO(2) above threshold values - back to similar to 1.1 Ga. These data suggest that pO(2) sufficient for the origin of animals was transiently in place well before their Neoproterozoic appearance, although uncertainty in the pO(2) threshold required for Cr-isotope fractionation precludes definitive biological interpretation. This study provides a proof of concept that the Cr-isotopic composition of carbonate rocks can provide important new constraints on the oxygen content of the ancient atmosphere. C1 [Gilleaudeau, G. J.; Frei, R.] Univ Copenhagen, Dept Geosci & Nat Resource Management, Oster Voldgade 10, DK-1350 Copenhagen, Denmark. [Gilleaudeau, G. J.] Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85281 USA. [Kaufman, A. J.] Univ Maryland, Dept Geol, College Pk, MD 20742 USA. [Kah, L. C.] Univ Tennessee, Dept Earth & Planetary Sci, Knoxville, TN 37996 USA. [Azmy, K.] Mem Univ Newfoundland, Dept Earth Sci, St John, NF A1B 3X5, Canada. [Bartley, J. K.] Gustavus Adolphus Coll, Dept Geol, St Peter, MN 56082 USA. [Chernyavskiy, P.] NCI, Biostat Radiat Epidemiol Branch, NIH, Rockville, MD 20850 USA. [Knoll, A. H.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. RP Gilleaudeau, GJ (reprint author), Univ Copenhagen, Dept Geosci & Nat Resource Management, Oster Voldgade 10, DK-1350 Copenhagen, Denmark.; Gilleaudeau, GJ (reprint author), Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85281 USA. EM ggillea1@gmail.com NR 26 TC 8 Z9 8 U1 5 U2 5 PU EUROPEAN ASSOC GEOCHEMISTRY PI PARIS CEDEX 05 PA IPGP-GOPEL-BUREAU 566, 1 RUE JUSSIEU, PARIS CEDEX 05, 75238, FRANCE SN 2410-339X EI 2410-3403 J9 GEOCHEM PERSPECT LET JI Geochem. Perspect. Lett. PY 2016 VL 2 IS 2 BP 178 EP 186 DI 10.7185/geochemlet.1618 PG 5 WC Geochemistry & Geophysics SC Geochemistry & Geophysics GA EA1JE UT WOS:000386347500008 ER PT J AU Vaughan, KL Mattison, JA AF Vaughan, Kelli L. Mattison, Julie A. TI Obesity and Aging in Humans and Nonhuman Primates: A Mini-Review SO GERONTOLOGY LA English DT Review DE Obesity; Diabetes; Animal model; Aging; Monkeys; Macaques ID RANDOMIZED CONTROLLED-TRIAL; DEPENDENT DIABETES-MELLITUS; HIGH-DOSE STREPTOZOTOCIN; MONKEYS MACACA-MULATTA; ALL-CAUSE MORTALITY; RHESUS-MONKEYS; CALORIE RESTRICTION; METABOLIC SYNDROME; INSULIN SENSITIVITY; GLUCOSE-TOLERANCE AB The prevalence of obesity in the US is increasing exponentially across gender, age and ethnic groups. Obesity and a long-term hypercaloric diet result in what appears to be accelerated aging, often leading to a multi-systemic deterioration known as the metabolic syndrome. Due to their physiological similarity to humans as well as comparable rates of spontaneous obesity and diabetes mellitus, nonhuman primates provide a useful translational model for the human condition. They allow for an in vivo study of disease progression, interaction of comorbidities, and novel interventions. However, defining obesity in aged humans and nonhuman primates is difficult as the physiological changes that occur with aging are not accounted for using our current systems (BMI body mass index and BCS body condition score). Nonetheless, nonhuman primate studies have greatly contributed to our understanding of obesity and metabolic dysfunction and should continue to play a large role in translational research. Here, methods for defining obesity and metabolic syndrome in humans and nonhuman primates are described along with the prevalence and effects of these conditions. (C) 2016 S. Karger AG, Basel C1 [Vaughan, Kelli L.; Mattison, Julie A.] NIA, Translat Gerontol Branch, Intramural Res Program, Poolesville, MD USA. [Vaughan, Kelli L.] SoBran Inc, Burtonsville, MD USA. RP Vaughan, KL (reprint author), NIA NHP Core, 16701 Elmer Sch Rd,Bldg 103,Room 1B04, Dickerson, MD 20842 USA. EM Kelli.Vaughan@nih.gov OI Vaughan, Kelli/0000-0001-5274-582X FU Intramural Research Program of the NIH, National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. NR 72 TC 0 Z9 0 U1 5 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X EI 1423-0003 J9 GERONTOLOGY JI Gerontology PY 2016 VL 62 IS 6 BP 611 EP 617 DI 10.1159/000445800 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA EA2IN UT WOS:000386416100006 PM 27120471 ER PT J AU Zhuang, WV Murabito, JM Lunetta, KL AF Zhuang, Wei Vivian Murabito, Joanne M. Lunetta, Kathryn L. TI Phenotypically Enriched Genotypic Imputation in Genetic Association Tests SO HUMAN HEREDITY LA English DT Article DE Genotype imputation; Missing genotypes; Missing data; Family studies; Family data; Association tests ID FAMILY-BASED ASSOCIATION; ADULT MALE TWINS; MISSING-DATA; LINKAGE ANALYSIS; MULTIPLE IMPUTATION; RARE VARIANTS; CUTTING LARGE; ERROR RATE; SEX; HERITABILITY AB Background: In longitudinal epidemiological studies there may be individuals with rich phenotype data who die or are lost to follow-up before providing DNA for genetic studies. Often, the genotypic and phenotypic data of the relatives are available. Two strategies for analyzing the incomplete data are to exclude ungenotyped subjects from analysis (the complete-case method, CC) and to include phenotyped but ungenotyped individuals in analysis by using relatives' genotypes for genotype imputation (GI). In both strategies, the information in the phenotypic data was not used to handle the missing-genotype problem. Methods: We propose a phenotypically enriched genotypic imputation (PEGI) method that uses the EM (expectation-maximization)-based maximum likelihood method to incorporate observed phenotypes into genotype imputation. Results: Our simulations with genotypes missing completely at random show that, for a single-nucleotide polymorphism (SNP) with moderate to strong effect on a phenotype, PEGI improves power more than GI without excess type I errors. Using the Framingham Heart Study data set, we compare the ability of the PEGI, GI, and CC to detect the associations between 5 SNPs and age at natural menopause. Conclusion: The PEGI method may improve power to detect an association over both CC and GI under many circumstances. (C) 2016 S. Karger AG, Basel. C1 [Zhuang, Wei Vivian; Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med, Boston, MA 02118 USA. [Murabito, Joanne M.] NHLBI, Framingham Heart Study, Boston, MA USA. [Zhuang, Wei Vivian] Creighton Univ, Sch Med, Dept Prevent Med & Publ Hlth, Omaha, NE USA. RP Zhuang, WV (reprint author), Creighton Univ, CHPE Bldg Rm 110,2500 Calif Plaza, Omaha, NE 68178 USA. EM VivianZhuang@creighton.edu FU National Institute of Aging [R01AG29451]; Affymetrix, Inc. [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Robert Dawson Evans Endowment of the Department of Medicine at Boston Medical Center; [N01-HC-25195] FX This project was supported by the National Institute of Aging (R01AG29451). The National Heart, Lung and Blood Institute's Framingham Heart Study is supported by Contract No. N01-HC-25195 and its contract with Affymetrix, Inc., for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Boston University School of Medicine and Boston Medical Center. NR 41 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2016 VL 81 IS 1 BP 35 EP 45 DI 10.1159/000446986 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA EA2IM UT WOS:000386416000004 PM 27576319 ER PT J AU Li, CL Sun, WW Feng, J Cao, J Zhang, P AF Li, Cai-Li Sun, Wen-Wen Feng, Jing Cao, Jie Zhang, Peng TI Utilization of rapid on-site evaluation (ROSE) in transbronchial needle aspiration (TBNA), it is not a simple statistical issue SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE LA English DT Review DE Transbronchial needle aspiration (TBNA); rapid on-site evaluation (ROSE); cytopathology; histopathology; endobronchial ultrasound (EBUS); staging of lung cancer ID LUNG-CANCER; CYTOLOGIC EVALUATION; MEDIASTINAL ADENOPATHY; BRONCHOGENIC-CARCINOMA; BIOPSY TECHNIQUES; RANDOMIZED-TRIAL; DIAGNOSIS; UTILITY; EXPERIENCE; BRONCHOSCOPY AB Transbronchial needle aspiration (TBNA) is widely accepted as a relatively minimally invasive, highly accurate and reliable procedure for a variety of malignant, infectious or granulomatous mediastinal and lung lesions. Rapid on-site evaluation (ROSE) guided TBNA is primarily used for staging pulmonary malignant lesions and for the diagnosis of unexplained mediastinal lymphadenopathy. The overall success rate of TBNA depends on quite a few factors, including size and the anatomic location of lymph nodes, number of biopsy sites and complications rate, characteristics of the lesion, skill of the aspirator, needle type used, underlying disease, prevalence of the disease being ascertained and the use of ancillary imaging techniques, etc. Specifically, the application of ROSE by cytopathologists may avoid additional sampling without compromising diagnostic yield with a preliminary evaluation for adequate diagnostic material and thus reduce the complication rate of TBNA procedure. In this review article we aimed at elaborate the technical details, clinical roles, cost performance, patient preference, and technological progress of ROSE in TBNA, highlighting the importance of ROSE with TBNA to gain the optimal sensitivity in obtaining histological diagnosis. We finally pointed out that it will be a tendency for a pulmonologist, to undergo a short yet intensive training, and perform ROSE guided TBNA with a high agreement with histopathological results, which may increase patient preference finally. C1 [Li, Cai-Li; Feng, Jing; Cao, Jie] Tianjin Med Univ, Gen Hosp, Dept Resp, Tianjin 300052, Peoples R China. [Sun, Wen-Wen; Zhang, Peng] Tianjin Med Univ, Grad Coll, Tianjin, Peoples R China. [Feng, Jing] NIEHS, Neuropharmacol Sect, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RP Feng, J; Cao, J (reprint author), Tianjin Med Univ, Gen Hosp, Dept Resp, Tianjin 300052, Peoples R China. EM zyyhxkfj@126.com; tjcaojie@126.com FU National Natural Science Foundation of China [81270144, 30800507, 81570844]; National Key Technology Research and Development Program of the Ministry of Science and Technology of China [2012BAI05B02] FX This study was supported by grants from the National Natural Science Foundation of China (81270144, 30800507, 81570844) and National Key Technology Research and Development Program of the Ministry of Science and Technology of China (2012BAI05B02). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 0 Z9 0 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1940-5901 J9 INT J CLIN EXP MED JI Int. J. Clin. Exp. Med. PY 2016 VL 9 IS 7 BP 13298 EP 13308 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EA2MT UT WOS:000386428400118 ER PT J AU Stewart, JM Viard, M Subramanian, HKK Roark, BK Afonin, KA Franco, E AF Stewart, Jaimie Marie Viard, Mathias Subramanian, Hari K. K. Roark, Brandon K. Afonin, Kirill A. Franco, Elisa TI Programmable RNA microstructures for coordinated delivery of siRNAs SO NANOSCALE LA English DT Article ID STRUCTURE PREDICTION; GOLD NANOPARTICLES; DNA NANOTUBES; DESIGN; NANOTECHNOLOGY; NANOSTRUCTURES; ASSEMBLIES; MOLECULES; ORIGAMI; SHAPES AB RNA is a natural multifunctional polymer, and is an essential component in both complex pathways and structures within the cellular environment. For this reason, artificial self-assembling RNA nanostructures are emerging as a powerful tool with broad applications in drug delivery and metabolic pathway regulation. To date, coordinated delivery of functional molecules via programmable RNA assemblies has been primarily done using nanosize RNA scaffolds. However, larger scaffolds could expand existing capabilities for spatial arrangement of ligands, and enable the controlled delivery of highly concentrated molecular loads. Here, we investigate whether micron-size RNA scaffolds can be assembled and further functionalized with different cargos (e.g. various siRNAs and fluorescent tags) for their synchronized delivery to diseased cells. Since known design approaches to build large RNA scaffolds are still underdeveloped, we apply a tiling method widely used in DNA nanotechnology. DNA tiles have been extensively used to build a variety of scalable and modular structures that are easily decorated with other ligands. Here, we adapt a double crossover (DX) DNA tile motif to design de novo DX RNA tiles that assemble and form lattices via programmed sticky end interactions. We optimize assembly protocols to guarantee high yield of RNA lattices. The resulting constructs are robust and modular with respect to the presence of distinct siRNAs and fluorophores. RNA tiles and lattices are successfully transfected in either human breast cancer or prostate cancer cells, where they efficiently knockdown the expression of target genes. Blood serum stability assays indicate that RNA lattices are more resilient to nuclease degradation when compared to individual tiles, thus making them better suited for therapeutic purposes. Overall, because of its design simplicity, we anticipate that this approach will be utilized for a wide range of applications in therapeutic RNA nanotechnology. C1 [Stewart, Jaimie Marie] Univ Calif Riverside, Dept Bioengn, Riverside, CA 92521 USA. [Viard, Mathias] Leidos Biomed Res Inc, Basic Sci Program, Gene Regulat & Chromosome Biol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Subramanian, Hari K. K.; Franco, Elisa] Univ Calif Riverside, Dept Mech Engn, Riverside, CA 92521 USA. [Roark, Brandon K.; Afonin, Kirill A.] Univ North Carolina Charlotte, Dept Chem, Nanoscale Sci Program, Charlotte, NC 28223 USA. [Roark, Brandon K.; Afonin, Kirill A.] Univ North Carolina Charlotte, Ctr Biomed Engn & Sci, Charlotte, NC 28223 USA. RP Franco, E (reprint author), Univ Calif Riverside, Dept Mech Engn, Riverside, CA 92521 USA.; Afonin, KA (reprint author), Univ North Carolina Charlotte, Dept Chem, Nanoscale Sci Program, Charlotte, NC 28223 USA.; Afonin, KA (reprint author), Univ North Carolina Charlotte, Ctr Biomed Engn & Sci, Charlotte, NC 28223 USA. EM kafonin@uncc.edu; efranco@ucr.edu FU U.S. National Science Foundation [DMR-1450747]; U.S. Department of Energy [SC0010595]; UNC Charlotte; Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN26120080001E]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This work has been funded in part by the U.S. National Science Foundation under CAREER grant DMR-1450747 to EF and by the U.S. Department of Energy under grant SC0010595 to EF. This work has been funded in part with the start-up funds provided by UNC Charlotte to KAA. This project has been funded in whole or in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN26120080001E. 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. The authors thank Dr Jeanette M. Bennett (UNCC) for sharing reagents. NR 46 TC 1 Z9 1 U1 3 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2016 VL 8 IS 40 BP 17542 EP 17550 DI 10.1039/c6nr05085a PG 9 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA EA0AA UT WOS:000386244400020 PM 27714127 ER PT J AU Chang, R Baria, AT Flounders, MW He, BJ AF Chang, Raymond Baria, Alexis T. Flounders, Matthew W. He, Biyu J. TI Unconsciously elicited perceptual prior SO NEUROSCIENCE OF CONSCIOUSNESS LA English DT Article DE perceptual prior; unconscious processing; Mooney images; visual masking; perceptual insight ID TOP-DOWN INFLUENCES; VISUAL-CORTEX; BRAIN; CONSCIOUSNESS; INFORMATION; MEMORY AB Increasing evidence over the past decade suggests that vision is not simply a passive, feed-forward process in which cortical areas relay progressivelymore abstract information to those higher up in the visual hierarchy, but rather an inferential process with top-down processes actively guiding and shaping perception. However, onemajor question that persists is whether such processes can be influenced by unconsciously perceived stimuli. Recent psychophysics and neuroimaging studies have revealed that while consciously perceived stimuli elicit stronger responses in higher visual and frontoparietal areas than those that fail to reach conscious awareness, the latter can still drive high-level brain and behavioral responses. We investigated whether unconscious processing of amasked natural image could facilitate subsequent conscious recognition of its degraded counterpart (a black-and-white "Mooney" image) presented many seconds later. We found that this is indeed the case, suggesting that conscious vision may be influenced by priors established by unconscious processing of a fleeting image. C1 [Chang, Raymond; Baria, Alexis T.; Flounders, Matthew W.; He, Biyu J.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Chang, Raymond] Cornell Univ, Weill Med Coll, New York, NY 10065 USA. [Baria, Alexis T.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [He, Biyu J.] NYU, Langone Med Ctr, Dept Neurol, Inst Neurosci, 550 1St Ave, New York, NY 10016 USA. [He, Biyu J.] NYU, Langone Med Ctr, Dept Neurosci & Physiol, Inst Neurosci, 550 1St Ave, New York, NY 10016 USA. [He, Biyu J.] NYU, Langone Med Ctr, Dept Radiol, Inst Neurosci, 550 1St Ave, New York, NY 10016 USA. RP He, BJ (reprint author), 550 1st Ave,MSB 460, New York, NY 10010 USA. EM biyu.jade.he@gmail.com OI He, Biyu/0000-0003-1549-1351 NR 24 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2057-2107 J9 NEUROSCI CONSCIOUS JI NEUROSCI. CONSCIOUS. PD JAN PY 2016 IS 1 AR niw008 DI 10.1093/nc/niw008 PG 9 WC Psychology, Biological SC Psychology GA DZ8PE UT WOS:000386132300010 ER PT J AU Maniscalco, B Lau, H AF Maniscalco, Brian Lau, Hakwan TI The signal processing architecture underlying subjective reports of sensory awareness SO NEUROSCIENCE OF CONSCIOUSNESS LA English DT Article DE awareness; consciousness; contents of consciousness; theories and models; perception; psychophysics ID TRANSCRANIAL MAGNETIC STIMULATION; DECISION CONFIDENCE; RECOGNITION MEMORY; UNCONSCIOUS INFORMATION; INHIBITORY CONTROL; PREFRONTAL CORTEX; VISUAL AWARENESS; ERROR-DETECTION; CONSCIOUSNESS; ACCURACY AB What is the relationship between perceptual information processing and subjective perceptual experience? Empirical dissociations between stimulus identification performance and subjective reports of stimulus visibility are crucial for shedding light on this question. We replicated a finding that metacontrast masking can produce such a dissociation (Lau and Passingham, 2006), and report a novel finding that this paradigm can also dissociate stimulus identification performance from the efficacy with which visibility ratings predict task performance. We explored various hypotheses about the relationship between perceptual task performance and visibility rating by implementing them in computational models and using formal model comparison techniques to assess which ones best captured the unusual patterns in the data. The models fell into three broad categories: Single Channel models, which hold that task performance and visibility ratings are based on the same underlying source of information; Dual Channel models, which hold that there are two independent processing streams that differentially contribute to task performance and visibility rating; and Hierarchical models, which hold that a late processing stage generates visibility ratings by evaluating the quality of early perceptual processing. Taking into account the quality of data fitting and model complexity, we found that Hierarchical models perform best at capturing the observed behavioral dissociations. Because current theories of visual awareness map well onto these different model structures, a formal comparison between them is a powerful approach for arbitrating between the different theories. C1 [Maniscalco, Brian] Columbia Univ, Dept Psychol, 1190 Amsterdam Ave,MC 5501, New York, NY 10027 USA. [Maniscalco, Brian] NINDS, NIH, 10 Ctr Dr,Bldg 10,Room 1D51A,MSC 1065, Bethesda, MD 20892 USA. [Lau, Hakwan] Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,Box 951563, Los Angeles, CA 90095 USA. RP Maniscalco, B (reprint author), NINDS, NIH, 10 Ctr Dr,Bldg 10,Room 1D51A,MSC 1065, Bethesda, MD 20892 USA. EM bmaniscalco@gmail.com NR 62 TC 3 Z9 3 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2057-2107 J9 NEUROSCI CONSCIOUS JI NEUROSCI. CONSCIOUS. PD JAN PY 2016 IS 1 AR niw002 DI 10.1093/nc/niw002 PG 17 WC Psychology, Biological SC Psychology GA DZ8PE UT WOS:000386132300004 ER PT J AU Yu, GC Zhao, R Wu, D Zhang, FW Shao, L Zhou, J Yang, J Tang, GP Chen, XY Huang, FH AF Yu, Guocan Zhao, Run Wu, Dan Zhang, Fuwu Shao, Li Zhou, Jiong Yang, Jie Tang, Guping Chen, Xiaoyuan Huang, Feihe TI Pillar[5]arene-based amphiphilic supramolecular brush copolymers: fabrication, controllable self-assembly and application in self-imaging targeted drug delivery SO POLYMER CHEMISTRY LA English DT Article ID RESONANCE ENERGY-TRANSFER; MOLECULAR RECOGNITION; POLYMER BRUSHES; ANTICANCER DRUG; CANCER-THERAPY; IN-VIVO; POLYPRODRUG AMPHIPHILES; GOLD NANOPARTICLES; CONTROLLED-RELEASE; PHOTONIC CRYSTALS AB Supramolecular brush copolymers have attracted continuing interest due to their unusual architectures, fascinating properties, and potential applications in many fields involving smart stimuli-responsive drug delivery systems. Herein, the first pillararene-based amphiphilic supramolecular brush copolymer (P5-PEG-Biotin superset of PTPE) was constructed on the basis of the host-guest molecular recognition between a water-soluble pillar[5] arene (P5) and a viologen salt (M). P5-PEG-Biotin superset of PTPE self-assembled into supramolecular nanoparticles (SNPs), which were utilized as a self-imaging drug delivery vehicle by taking advantage of the aggregation-induced emission (AIE) effect. Encapsulation of anticancer drug doxorubicin (DOX) caused deactivation of the fluorescence of both the tetraphenylethene (TPE) and DOX chromophores due to the energy transfer relay (ETR) effect, mediated by Forster resonance energy transfer (FRET) and aggregation-caused quenching (ACQ). The release of loaded DOX molecules can be triggered by low pH and reductase, recovering the "silenced" fluorescence caused by the interruption of the ETR effect, achieving in situ visualization of the drug release process by observing the location and magnitude of the energy transfer-dependent fluorescence variation. The biotin ligands on the surfaces of the DOX-loaded SNPs act as targeting agents to deliver DOX preferentially to cancer cells over-expressing biotin receptors. In vitro studies demonstrated that the loading of DOX by this supramolecular nanomaterial exhibited selective cytotoxicity towards cancer cells over normal cells. The potency of this sophisticated supramolecular drug delivery system in cancer therapy was further evaluated in HeLa tumorbearing mice. In vivo experiments confirmed that the DOX-loaded SNPs possess excellent antitumor efficacy with negligible systemic toxicity. C1 [Yu, Guocan; Zhao, Run; Shao, Li; Zhou, Jiong; Yang, Jie; Huang, Feihe] Zhejiang Univ, Dept Chem, Ctr Chem High Performance & Novel Mat, State Key Lab Chem Engn, Hangzhou 310027, Peoples R China. [Wu, Dan; Tang, Guping] Zhejiang Univ, Dept Chem, Inst Chem Biol & Pharmaceut Chem, Hangzhou 310027, Peoples R China. [Yu, Guocan; Zhang, Fuwu; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Huang, FH (reprint author), Zhejiang Univ, Dept Chem, Ctr Chem High Performance & Novel Mat, State Key Lab Chem Engn, Hangzhou 310027, Peoples R China.; Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov; fhuang@zju.edu.cn RI Zhou, Jiong/R-2146-2016; Huang, Feihe/A-1020-2012; yang, jie/A-5219-2016 OI Huang, Feihe/0000-0003-3177-6744; yang, jie/0000-0001-9970-7505 FU National Basic Research Program [2013CB834502]; National Natural Science Foundation of China [21434005, 91527301, J1210042]; Fundamental Research Funds for the Central Universities; Key Science Technology Innovation Team of Zhejiang Province [2013TD02]; Open Project of the State Key Laboratory of Supramolecular Structure and Materials [sklssm201611]; Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering; National Institutes of Health FX This work was supported by the National Basic Research Program (2013CB834502), the National Natural Science Foundation of China (21434005, 91527301, and J1210042), the Fundamental Research Funds for the Central Universities, the Key Science Technology Innovation Team of Zhejiang Province (2013TD02), the Open Project of the State Key Laboratory of Supramolecular Structure and Materials (sklssm201611), the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, and the National Institutes of Health. NR 98 TC 9 Z9 9 U1 51 U2 51 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1759-9954 EI 1759-9962 J9 POLYM CHEM-UK JI Polym. Chem. PY 2016 VL 7 IS 40 BP 6178 EP 6188 DI 10.1039/c6py01402j PG 11 WC Polymer Science SC Polymer Science GA DZ9SS UT WOS:000386219800005 PM 27795740 ER PT J AU Pluta, RM AF Pluta, Ryszard M. TI To Be-et, or Not to Be-et, That is the Question: The Role(s) of Nitrate and Nitrite in Health and Illness SO REVIEWS ON RECENT CLINICAL TRIALS LA English DT Article DE Heart attack; nitrate; nitric oxide; nitrite; stroke ID IMPROVES EXERCISE TOLERANCE; VIVO ISCHEMIA-REPERFUSION; O-2 UPTAKE KINETICS; DIETARY NITRATE; BLOOD-PRESSURE; BEETROOT JUICE; SODIUM-NITRITE; IN-VIVO; INORGANIC NITRATE; HYPOXIC VASODILATION AB Background: This manuscript addresses the multilevel role of dietary nitrate and nitrite in health and diseases because of increased interest in dietary supplementation. Method: Review of research devoted to both beneficial but also possible deleterious effects of uncontrolled indigestion of red beet-root juice and other sources of high concentrated nitrate and nitrite. Results: The body of evidence strongly suggested that persons using nitrate/nitrite supplementation and particularly patients treated with sodium nitrite, having kidney disease or impaired methemoglobin reeducates activity, should closely monitor nitrate/nitrite indigestion. Conclusion: Oral intake of red beet-root juice, green leaved veggies, cured meat, as well as urine excretion of nitrate/nitrite, methemoglobin reeducates activity should be carefully assessed especially in patients treated with sodium nitrite. C1 [Pluta, Ryszard M.] NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM ryszardpluta@me.com NR 90 TC 0 Z9 0 U1 6 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1574-8871 EI 1876-1038 J9 REV RECENT CLIN TRIA JI Rev. Recent Clin. Trials PY 2016 VL 11 IS 2 BP 135 EP 140 DI 10.2174/1574887111666160330113803 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA EA1FG UT WOS:000386337300010 PM 27028972 ER PT J AU Ceger, P Allen, D Huang, RL Xia, MH Casey, W AF Ceger, Patricia Allen, David Huang, Ruili Xia, Menghang Casey, Warren TI Performance of the BG1Luc ER TA Method in a qHTS Format (vol 32, pg 287, 2015) SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Correction C1 [Ceger, Patricia; Allen, David] Integrated Lab Syst Inc, Res Triangle Pk, NC USA. [Huang, Ruili; Xia, Menghang] NIH, Natl Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD USA. [Casey, Warren] NIEHS, Natl Toxicol Program, Interagency Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. RP Ceger, P (reprint author), Integrated Lab Syst Inc, Res Triangle Pk, NC USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH PI HEILDEBERG PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY SN 1868-596X EI 1868-8551 J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2016 VL 33 IS 1 BP 79 EP 79 DI 10.14573/altex.1512041 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DZ0EO UT WOS:000385510500019 PM 26776439 ER PT J AU Ball, N Cronin, MTD Shen, J Blackburn, K Booth, ED Bouhifd, M Donley, E Egnash, L Hastings, C Juberg, DR Kleensang, A Kleinstreuer, N Kroese, ED Lee, AC Luechtefeld, T Maertens, A Marty, S Naciff, JM Palmer, J Pamies, D Penman, M Richarz, AN Russo, DP Stuard, SB Patlewicz, G van Ravenzwaay, B Wu, SD Zhu, H Hartung, T AF Ball, Nicholas Cronin, Mark T. D. Shen, Jie Blackburn, Karen Booth, Ewan D. Bouhifd, Mounir Donley, Elizabeth Egnash, Laura Hastings, Charles Juberg, Daland R. Kleensang, Andre Kleinstreuer, Nicole Kroese, E. Dinant Lee, Adam C. Luechtefeld, Thomas Maertens, Alexandra Marty, Sue Naciff, Jorge M. Palmer, Jessica Pamies, David Penman, Mike Richarz, Andrea-Nicole Russo, Daniel P. Stuard, Sharon B. Patlewicz, Grace van Ravenzwaay, Bennard Wu, Shengde Zhu, Hao Hartung, Thomas TI Toward Good Read-Across Practice (GRAP) Guidance SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Article DE computational toxicology; chemical similarity; read-across; hazard assessment; uncertainty ID DECISION-MAKING FRAMEWORKS; CHEMICAL SAFETY ASSESSMENT; RISK-ASSESSMENT; REPRODUCTIVE TOXICITY; CHEMISTRY DATABASES; HAZARD ASSESSMENT; CELL-CULTURE; NANOMATERIALS; TOXICOLOGY; FOOD AB Grouping of substances and utilizing read-across of data within those groups represents an important data gap filling technique for chemical safety assessments. Categories/analogue groups are typically developed based on structural similarity and, increasingly often, also on mechanistic (biological) similarity. While read-across can play a key role in complying with legislation such as the European REACH regulation, the lack of consensus regarding the extent and type of evidence necessary to support it often hampers its successful application and acceptance by regulatory authorities. Despite a potentially broad user community, expertise is still concentrated across a handful of organizations and individuals. In order to facilitate the effective use of read-across, this document presents the state of the art, summarizes insights learned from reviewing ECHA published decisions regarding the relative successes/pitfalls surrounding read-across under REACH, and compiles the relevant activities and guidance documents. Special emphasis is given to the available existing tools and approaches, an analysis of ECHA's published final decisions associated with all levels of compliance checks and testing proposals, the consideration and expression of uncertainty, the use of biological support data, and the impact of the ECHA Read-Across Assessment Framework (RAAF) published in 2015. C1 [Ball, Nicholas; Juberg, Daland R.; Marty, Sue] Dow Chem Co USA, Midland, MI 48674 USA. [Ball, Nicholas; Juberg, Daland R.; Marty, Sue] Dow AgroSci, Indianapolis, IN USA. [Cronin, Mark T. D.; Richarz, Andrea-Nicole] Liverpool John Moores Univ, Sch Pharm & Biomol Sci, Liverpool, Merseyside, England. [Shen, Jie] Res Inst Fragrance Mat Inc, Woodcliff Lake, NJ USA. [Blackburn, Karen; Naciff, Jorge M.; Stuard, Sharon B.; Wu, Shengde] Procter & Gamble Co, Cincinnati, OH USA. [Booth, Ewan D.] Syngenta Ltd, Jealotts Hill Int Res Ctr, Bracknell, Berks, England. [Bouhifd, Mounir; Kleensang, Andre; Luechtefeld, Thomas; Maertens, Alexandra; Pamies, David; Hartung, Thomas] Johns Hopkins Bloomberg Sch Publ Hlth, CAAT, Baltimore, MD USA. [Donley, Elizabeth; Egnash, Laura; Palmer, Jessica] Stemina Biomarker Discovery Inc, Madison, WI USA. [Hastings, Charles] BASF SE, Ludwigshafen, Germany. [Hastings, Charles] BASF SE, Res Triangle Pk, NC USA. [Kleinstreuer, Nicole] NIEHS, Natl Toxicol Program, Interagency Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. [Kroese, E. Dinant; van Ravenzwaay, Bennard] TNO, Risk Anal Prod Dev, Zeist, Netherlands. [Lee, Adam C.] DuPont Haskell Global Ctr Hlth, Newark, NJ USA. [Lee, Adam C.] DuPont Haskell Global Ctr Environm Sci, Newark, NJ USA. [Penman, Mike] Penman Consulting, Brussels, Belgium. [Russo, Daniel P.; Zhu, Hao] Rutgers State Univ, Dept Chem, Camden, NJ USA. [Russo, Daniel P.; Zhu, Hao] Rutgers State Univ, Ctr Computat & Integrat Biol, Camden, NJ USA. [Patlewicz, Grace] US EPA, ORD, Natl Ctr Computat Toxicol, Res Triangle Pk, NC USA. [Hartung, Thomas] Univ Konstanz, CAAT Europe, Constance, Germany. RP Hartung, T (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing, 615 North Wolfe St, Baltimore, MD 21205 USA. EM thartun1@jhu.edu OI Kleensang, Andre/0000-0002-4564-7399; Kleinstreuer, Nicole/0000-0002-7914-3682 FU NIEHS training grant [T32 ES007141]; EU Horizon 2020 project EUToxRisk FX The input and valuable discussion by Dr David Steup, Shell, as well as Moyinoluwa D. Adenuga and James J. Freeman, Exxon-Mobil Biomedical Sciences, is gratefully appreciated. T.L. was supported by NIEHS training grant (T32 ES007141). Support from the EU Horizon 2020 project EUToxRisk is gratefully appreciated. NR 76 TC 11 Z9 11 U1 6 U2 7 PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH PI HEILDEBERG PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY SN 1868-596X EI 1868-8551 J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2016 VL 33 IS 2 BP 149 EP 166 DI 10.14573/altex.1601251 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DZ0FI UT WOS:000385512500007 PM 26863606 ER PT J AU Zhu, H Bouhifd, M Donley, E Egnash, L Kleinstreuer, N Kroese, ED Liu, ZC Luechtefeld, T Palmer, J Pamies, D Shen, J Strauss, V Wu, SD Hartung, T AF Zhu, Hao Bouhifd, Mounir Donley, Elizabeth Egnash, Laura Kleinstreuer, Nicole Kroese, E. Dinant Liu, Zhichao Luechtefeld, Thomas Palmer, Jessica Pamies, David Shen, Jie Strauss, Volker Wu, Shengde Hartung, Thomas TI Supporting Read-Across Using Biological Data SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Article DE read-across; biological similarity; safety assessment; big data ID COMPARATIVE TOXICOGENOMICS DATABASE; COMPUTATIONAL TOXICOLOGY RESOURCE; DETECTING REPRODUCTIVE TOXICANTS; ADVERSE OUTCOME PATHWAY; VITRO TEST BATTERY; IN-VITRO; RISK-ASSESSMENT; ENVIRONMENTAL CHEMICALS; DEVELOPMENTAL TOXICITY; SCREENING ASSAYS AB Read-across, i.e., filling toxicological data gaps by relating to similar chemicals for which test data are available, is usually done based on chemical similarity. Besides structure and physico-chemical properties, biological similarity based on biological data adds extra strength to this process. In the simplest case, chemically similar substances also show similar test results in relevant in vitro assays. This is a well-established method for the read-across of, e.g., genotoxicity assays. Larger datasets of biological and toxicological properties of hundreds and thousands of substances are becoming available, enabling big data approaches in read-across studies. In the context of developing Good Read-Across Practice guidance, a number of case studies using various big data sources were evaluated to assess the contribution of biological data to enriching read-across. An example is given for the US EPA's ToxCast dataset which allows read-across for high quality uterotrophic assays for estrogenic endocrine disruption. Similarly, an example is given for REACH registration data that enhances read-across for acute toxicity studies. A different approach is taken using omics data to establish biological similarity: Examples are given for in vitro stem cell models and short-term in vivo repeated dose studies in rats used to support read-across and category formation. These preliminary biological data-driven read-across studies show the way towards the generation of new read-across approaches that can inform chemical safety assessment. C1 [Zhu, Hao] Rutgers State Univ, Dept Chem, Camden, NJ USA. [Zhu, Hao] Rutgers State Univ, Ctr Computat & Integrat Biol, Camden, NJ USA. [Bouhifd, Mounir; Luechtefeld, Thomas; Pamies, David; Hartung, Thomas] Johns Hopkins Bloomberg Sch Publ Hlth, CAAT, Baltimore, MD USA. [Donley, Elizabeth; Egnash, Laura; Palmer, Jessica] Stemina Biomarker Discovery Inc, Madison, WI USA. [Kleinstreuer, Nicole] NIEHS, Natl Toxicol Program, Interagency Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. [Kroese, E. Dinant] TNO, Risk Anal Prod Dev, Zeist, Netherlands. [Liu, Zhichao] US FDA, NCTR, Little Rock, AR USA. [Shen, Jie] Res Inst Fragrance Mat Inc, Woodcliff Lake, NJ USA. [Strauss, Volker] BASF Aktiengesellsch Expt Toxicol & Ecol, Ludwigshafen, Germany. [Wu, Shengde] Procter & Gamble, Cincinnati, OH USA. [Hartung, Thomas] Univ Konstanz, CAAT Europe, Constance, Germany. RP Hartung, T (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing, 615 North Wolfe St, Baltimore, MD 21205 USA. EM thartun1@jhu.edu OI Kleinstreuer, Nicole/0000-0002-7914-3682 FU NIEHS training grant [T32 ES007141]; EU Horizon 2020 project EUToxRisk FX T.L. was supported by NIEHS training grant (T32 ES007141). Support from the EU Horizon 2020 project EUToxRisk is gratefully appreciated. NR 110 TC 7 Z9 7 U1 8 U2 9 PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH PI HEILDEBERG PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY SN 1868-596X EI 1868-8551 J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2016 VL 33 IS 2 BP 167 EP 182 DI 10.14573/altex.1601252 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DZ0FI UT WOS:000385512500008 PM 26863516 ER PT J AU Marx, U Andersson, TB Bahinski, A Beilmann, M Beken, S Cassee, FR Cirit, M Daneshian, M Fitzpatrick, S Frey, O Gaertner, C Giese, C Griffith, L Hartung, T Heringa, MB Hoeng, J de Jong, WH Kojima, H Kuehnl, J Leist, M Luch, A Maschmeyer, I Sakharov, D Sips, AJAM Steger-Hartmann, T Tagle, DA Tonevitsky, A Tralau, T Tsyb, S van de Stolpe, A Vandebriel, R Vulto, P Wang, JF Wiest, J Rodenburg, M Roth, A AF Marx, Uwe Andersson, Tommy B. Bahinski, Anthony Beilmann, Mario Beken, Sonja Cassee, Flemming R. Cirit, Murat Daneshian, Mardas Fitzpatrick, Susan Frey, Olivier Gaertner, Claudia Giese, Christoph Griffith, Linda Hartung, Thomas Heringa, Minne B. Hoeng, Julia de Jong, Wim H. Kojima, Hajime Kuehnl, Jochen Leist, Marcel Luch, Andreas Maschmeyer, Ilka Sakharov, Dmitry Sips, Adrienne J. A. M. Steger-Hartmann, Thomas Tagle, Danilo A. Tonevitsky, Alexander Tralau, Tewes Tsyb, Sergej van de Stolpe, Anja Vandebriel, Rob Vulto, Paul Wang, Jufeng Wiest, Joachim Rodenburg, Marleen Roth, Adrian TI Biology-Inspired Microphysiological System Approaches to Solve the Prediction Dilemma of Substance Testing SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Editorial Material DE microphysiological systems; organ-on-a-chip; in vitro models; predictive toxicology; drug testing ID ON-A-CHIP; PLURIPOTENT STEM-CELLS; SKIN SENSITIZATION POTENCY; NEURAL-NETWORK ANALYSIS; LYMPH-NODE ASSAY; MULTI-ORGAN-CHIP; IN-VITRO MODELS; SCREENING CONTACT ALLERGENS; OF-THE-ART; MICROFLUIDIC DEVICE AB The recent advent of microphysiological systems-microfluidic biomimetic devices that aspire to emulate the biology of human tissues, organs and circulation in vitro-promises to enable a global paradigm shift in drug development. An extraordinary US government initiative and various dedicated research programs in Europe and Asia recently have led to the first cutting-edge achievements of human single-organ and multi-organ engineering based on microphysiological systems. The expectation is that test systems established on this basis will model various disease stages and predict toxicity, immunogenicity, ADME profiles and treatment efficacy prior to clinical testing. Consequently, this technology could significantly affect the way drug substances are developed in the future. Furthermore, microphysiological system-based assays may revolutionize our current global programs of prioritization of hazard characterization for any new substances to be used, for example, in agriculture, food, ecosystems or cosmetics, thus replacing the use of laboratory animal models. Here, thirty-six experts from academia, industry and regulatory bodies present the results of an intensive workshop (held in June 2015, Berlin, Germany). They review the status quo of microphysiological systems available today against industry needs, and assess the broad variety of approaches with fit-for-purpose potential in the drug development cycle. Feasible technical solutions to reach the next levels of human biology in vitro are proposed. Furthermore, key organ-on-a-chip case studies as well as various national and international programs are highlighted. Finally, a roadmap into the future towards more predictive and regulatory-accepted substance testing on a global scale is outlined. C1 [Marx, Uwe; Maschmeyer, Ilka] TissUse GmbH, Berlin, Germany. [Andersson, Tommy B.] AstraZeneca, Cardiovasc & Metab Dis Innovat Med & Early Dev Bi, Molndal, Sweden. [Andersson, Tommy B.] Karolinska Inst, Dept Physiol & Pharmacol, Pharmacogenet Sect, Stockholm, Sweden. [Bahinski, Anthony] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Beilmann, Mario] Boehringer Ingelheim Pharma GmbH & Co KG, Nonclin Drug Safety, Biberach, Germany. [Beken, Sonja] Fed Agcy Med & Hlth Prod, Brussels, Belgium. [Cassee, Flemming R.; Heringa, Minne B.; de Jong, Wim H.; Sips, Adrienne J. A. M.; Vandebriel, Rob; Rodenburg, Marleen] Natl Inst Publ Hlth & Environm, Bilthoven, Netherlands. [Cassee, Flemming R.] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. [Cirit, Murat; Griffith, Linda] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Daneshian, Mardas; Hartung, Thomas; Leist, Marcel] Univ Konstanz, Ctr Alternat Anim Testing Europe, Constance, Germany. [Fitzpatrick, Susan] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Frey, Olivier] Swiss Fed Inst Technol, Bio Engn Lab, Dept Biosyst Sci & Engn, Basel, Switzerland. [Gaertner, Claudia] Microfluid ChipShop GmbH, Jena, Germany. [Giese, Christoph] ProBioGen AG, Berlin, Germany. [Hartung, Thomas] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing, Baltimore, MD USA. [Hoeng, Julia] Philip Morris Int R&D, Neuchatel, Switzerland. [Kojima, Hajime] Japanese Ctr Validat Anim Methods, Tokyo, Japan. [Kuehnl, Jochen] Beiersdorf, Hamburg, Germany. [Luch, Andreas; Tralau, Tewes] German Fed Inst Risk Assessment, Dept Chem & Prod Safety, Berlin, Germany. [Sakharov, Dmitry] Sci Res Ctr Bioclinicum, Moscow, Russia. [Steger-Hartmann, Thomas] Bayer, Invest Toxicol, Berlin, Germany. [Tagle, Danilo A.] Natl Ctr Adv Translat Sci, NIH, Bethesda, MD USA. [Tonevitsky, Alexander] Natl Ctr Med Radiol Res, Moscow, Russia. [Tsyb, Sergej] Russian Minist Prod & Trade, Moscow, Russia. [van de Stolpe, Anja] Inst Human Organ & Dis Model Technol, Leiden, Netherlands. [Vulto, Paul] MIMETAS BV, Leiden, Netherlands. [Wang, Jufeng] Chinese Natl Ctr Safety Evaluat Drugs, Beijing, Peoples R China. [Wiest, Joachim] Cellasys GmbH, Kronburg, Germany. [Roth, Adrian] F Hoffmann La Roche Ltd, Roche Innovat Ctr Basel, Basel, Switzerland. RP Marx, U (reprint author), TissUse GmbH, Berlin, Germany. EM Uwe.marx@tissuse.com RI Frey, Olivier/G-7065-2011; Leist, Marcel/D-2133-2010; OI Frey, Olivier/0000-0002-4259-3751; Leist, Marcel/0000-0002-3778-8693; Wiest, Joachim/0000-0003-4372-9523; Tonevitsky, Alexander/0000-0002-7079-7145 NR 374 TC 6 Z9 6 U1 17 U2 17 PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH PI HEILDEBERG PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY SN 1868-596X EI 1868-8551 J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2016 VL 33 IS 3 BP 272 EP 321 DI 10.14573/altex.1603161 PG 50 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DZ0FW UT WOS:000385513900008 PM 27180100 ER PT S AU Sergeev, R Kavaliou, I Gabrielian, A Rosenthal, A Tuzikov, A AF Sergeev, Roman Kavaliou, Ivan Gabrielian, Andrei Rosenthal, Alex Tuzikov, Alexander BE Bourgeois, A Skums, P Wan, X Zelikovsky, A TI Methods for Genome-Wide Analysis of MDR and XDR Tuberculosis from Belarus SO BIOINFORMATICS RESEARCH AND APPLICATIONS, ISBRA 2016 SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT 12th International Symposium on Bioinformatics Research and Applications (ISBRA) CY JUN 05-08, 2016 CL Minsk, BYELARUS DE Genome-wide association study; Multi drug-resistant tuberculosis; Genotype; Single nucleotide polymorphisms ID MYCOBACTERIUM-TUBERCULOSIS; DRUG SUSCEPTIBILITY; ASSOCIATION; RESISTANCE AB Emergence of drug-resistant microorganisms has been recognized as a serious threat to public health since the era of chemotherapy began. This problem is extensively discussed in the context of tuberculosis treatment. Alterations in pathogen genomes are among the main mechanisms by which microorganisms exhibit drug resistance. Analysis of the reported cases and discovery of new resistance-associated mutations may contribute greatly to the development of new drugs and effective therapy management. The proposed methodology allows identifying genetic changes and assessing their contribution to resistance phenotypes. C1 [Sergeev, Roman; Kavaliou, Ivan; Tuzikov, Alexander] United Inst Informat Problems NASB, 6 Surganov Str, Minsk 220012, Byelarus. [Gabrielian, Andrei; Rosenthal, Alex] NIAID, Off Cyber Infrastruct & Computat Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Kavaliou, Ivan] EPAM Syst, 1-1 Acad Kuprevich Str, Minsk 220141, Byelarus. RP Sergeev, R (reprint author), United Inst Informat Problems NASB, 6 Surganov Str, Minsk 220012, Byelarus. EM roma.sergeev@gmail.com NR 16 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-38782-6; 978-3-319-38781-9 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2016 VL 9683 BP 258 EP 268 DI 10.1007/978-3-319-38782-6_22 PG 11 WC Biochemical Research Methods; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BF9NQ UT WOS:000385788800022 ER PT J AU Flegel, WA de Castilho, SL Keller, MA Klapper, EB Moulds, JM Noizat-Pirenne, F Shehata, N Stack, G St-Louis, M Tormey, CA Waxman, DA Weinstock, C Wendel, S Denomme, GA AF Flegel, Willy A. de Castilho, Shirley L. Keller, Margaret A. Klapper, Ellen B. Moulds, Joann M. Noizat-Pirenne, France Shehata, Nadine Stack, Gary St-Louis, Maryse Tormey, Christopher A. Waxman, Dan A. Weinstock, Christof Wendel, Silvano Denomme, Gregory A. TI Molecular immunohaematology round table discussions at the AABB Annual Meeting, Philadelphia 2014 SO BLOOD TRANSFUSION LA English DT Editorial Material ID ANTI-D IMMUNIZATION; ROOT CAUSE ANALYSIS; BLOOD-DONORS; MASSIVE TRANSFUSION; TIME; SPECTROMETRY; PHENOTYPE; ERROR C1 [Flegel, Willy A.] NIH, Dept Transfus Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. [de Castilho, Shirley L.] HEMORIO, Blood Bank, Rio De Janeiro, Brazil. [Keller, Margaret A.] Amer Red Cross, Philadelphia, PA USA. [Klapper, Ellen B.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Moulds, Joann M.] Grifols, San Marcos, TX USA. [Noizat-Pirenne, France] EFS Ile de France, Creteil, France. [Shehata, Nadine] Mt Sinai Hosp, Toronto, ON, Canada. [Stack, Gary; Tormey, Christopher A.] Yale Univ, Sch Med, New Haven, CT USA. [St-Louis, Maryse] Hema Quebec, Quebec City, PQ, Canada. [Waxman, Dan A.] Indiana Blood Ctr, Indianapolis, IN USA. [Weinstock, Christof] German Red Cross Blood Serv Baden Wurttemberg Hes, Inst Clin Transfus Med & Immunogenet Ulm, Ulm, Germany. [Weinstock, Christof] Univ Ulm, D-89069 Ulm, Germany. [Wendel, Silvano] Hosp Sirio Libanes, Sao Paulo, Brazil. [Denomme, Gregory A.] Blood Ctr Wisconsin, Milwaukee, WI USA. RP Flegel, WA (reprint author), NIH, Dept Transfus Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. EM waf@nih.gov OI Denomme, Gregory/0000-0001-8727-1679 NR 27 TC 1 Z9 1 U1 1 U2 1 PU SIMITI SERVIZI SRL PI MILAN PA VIA DESIDERIO 21, MILAN, 20131, ITALY SN 1723-2007 J9 BLOOD TRANSFUS-ITALY JI Blood Transf. PY 2016 VL 14 IS 5 BP 425 EP 433 DI 10.2450/2015.0130-15 PG 9 WC Hematology SC Hematology GA DY8HW UT WOS:000385371200007 PM 26710354 ER PT J AU Buster, TW Chernyavskiy, P Harms, NR Kaste, EG Burnfield, JM AF Buster, Thad W. Chernyavskiy, Pavel Harms, Nolan R. Kaste, E. Grace Burnfield, Judith M. TI Computerized dynamic posturography detects balance deficits in individuals with a history of chronic severe traumatic brain injury SO BRAIN INJURY LA English DT Article DE Traumatic brain injury; rehabilitation; assessment; measurement; disability ID RATING-SCALE RESPONSIVENESS; COMMUNITY-DWELLING PERSONS; RELIABILITY; STROKE; VALIDITY; REHABILITATION; PROBABILITY; FALLS; GAIT AB Background: Mild balance deficits can be challenging to detect in individuals with long-standing traumatic brain injuries. This study compared Computerized Dynamic Posturography (CDP) scores from individuals with traumatic brain injuries (TBI) to controls to determine if CDP could differentiate between the two groups and determine if there was a learning effect associated with testing that could be used to guide evaluation of baseline balance.Methods: Ten ambulatory individuals with a history of severe TBI and 10 individuals without participated in three CDP sessions (24-72 hours apart). During each session, participants performed the Berg Balance Test, Dynamic Gait Index and three trials of a standardized balance assessment and Dynamic Movement Analysis (DMA) scores were recorded for each test.Results: Individuals with TBI scored 93% higher (i.e. reflecting poorer balance) than the control group. The group with TBI exhibited 6.6-times more variability compared to the control group, with estimated variances of 0.3407 and 0.0517, respectively. A learning effect was detected in the group with TBI on the first day of testing ((TBI F) = -0.1241, p-value < 0.01).Discussion: The CDP system detected balance differences between individuals with TBI and controls. Given the documented learning effect, the best of three trials should be used to accurately assess baseline scores. C1 [Buster, Thad W.; Burnfield, Judith M.] Madonna Rehabil Hosp, Inst Rehabil Sci & Engn, Movement & Neurosci Ctr, Lincoln, NE 68506 USA. [Chernyavskiy, Pavel] NCI, Radiat Epidemiol Branch, NIH, Rockville, MD USA. [Chernyavskiy, Pavel] NCI, Biostat Branch, NIH, Rockville, MD USA. [Harms, Nolan R.] Concordia Univ, Hlth & Human Performance Dept, Seward, NE USA. [Kaste, E. Grace] Ohio State Univ, Sch Hlth & Rehabil Sci, Columbus, OH 43210 USA. RP Buster, TW (reprint author), Madonna Rehabil Hosp, Inst Rehabil Sci & Engn, 5401 South St, Lincoln, NE 68506 USA. EM tbuster@madonna.org NR 41 TC 0 Z9 0 U1 2 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PY 2016 VL 30 IS 10 BP 1249 EP 1255 DI 10.1080/02699052.2016.1183822 PG 7 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DX4BR UT WOS:000384324300013 PM 27386896 ER PT J AU Simone, BA Dan, T Palagani, A Jin, LJ Han, SY Wright, C Savage, JE Gitman, R Lim, MK Palazzo, J Mehta, MP Simone, NL AF Simone, Brittany A. Tu Dan Palagani, Ajay Jin, Lianjin Han, Sunny Y. Wright, Christopher Savage, Jason E. Gitman, Robert Lim, Meng Kieng Palazzo, Juan Mehta, Minesh P. Simone, Nicole L. TI Caloric restriction coupled with radiation decreases metastatic burden in triple negative breast cancer SO CELL CYCLE LA English DT Article DE breast cancer; Caloric restriction; metastases ID FACTOR-I RECEPTOR; MONOCLONAL-ANTIBODY; MAMMARY-TUMORS; SOLID TUMORS; GROWTH; CELLS; EXPRESSION; MICE; INHIBITOR; MELANOMA AB Purpose: Metastatic breast cancer is devastating and triple negative breast cancers (TNBC) have a higher propensity for metastasis. Improved local control upfront in this aggressive cancer could potentially decrease its propensity toward metastasis. We sought to determine if using caloric restriction (CR) as a systemic therapy, combined with radiation therapy (IR) to the primary tumor, may impact metastatic disease. Methods: An orthotopic mouse model using a highly metastatic, luciferase-tagged TNBC cell line (4T1), was used to generate palpable tumors. Mice were then treated with CR, IR, and a combination of the two. In vivo imaging was performed for metastatic evaluation. Molecular evaluation of the tumors was performed, generating a mechanistic hypothesis for CR, which was then tested with pertinent pathway inhibition in the model. Results: CR significantly increased the time to developing metastases, decreased the overall number and volume of lung metastases, and increased survival. CR decreased proliferation, increased apoptosis and globally downregulated the IGF-1R signaling pathway. Adding an IGF-1R/INSR inhibitor to local IR in vivo accomplished a decrease in metastases similar to CR plus IR, demonstrating the importance of the IGF-1R signaling pathway, and underscoring it as a possible mechanism for CR. Conclusions: CR decreased metastatic burden and therefore may complement cytotoxic therapies being used in the clinical setting for metastatic disease. Downregulation of the IGF-1R pathway, is in part responsible for this response and modulating IGF-1R directly resulted in similar improved progression-free survival. The novel use of CR has the potential to enhance clinical outcomes for patients with metastatic breast cancer. C1 [Simone, Brittany A.; Tu Dan; Palagani, Ajay; Jin, Lianjin; Han, Sunny Y.; Wright, Christopher; Gitman, Robert; Lim, Meng Kieng; Simone, Nicole L.] Thomas Jefferson Univ, Dept Radiat Oncol, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. [Savage, Jason E.] NCI, Radiat Oncol Branch, Bldg 10, Bethesda, MD 20892 USA. [Palazzo, Juan] Thomas Jefferson Univ, Dept Pathol, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. [Mehta, Minesh P.] Miami Canc Inst, Dept Radiat Oncol, Miami, FL USA. RP Simone, NL (reprint author), Thomas Jefferson Univ, Dept Radiat Oncol, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. EM nicole.simone@jeffersonhospital.org FU American Cancer Society [IRG - 08-060-04]; ASTRO Junior Faculty Award; Kimmel Cancer Center's NCI Cancer Center Support Grant [P30 CA56036] FX Research support was in part through Grant # IRG - 08-060-04 from the American Cancer Society, in part by the ASTRO Junior Faculty Award, and in part by the Kimmel Cancer Center's NCI Cancer Center Support Grant P30 CA56036. NR 41 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2016 VL 15 IS 17 BP 2265 EP 2274 DI 10.1080/15384101.2016.1160982 PG 10 WC Cell Biology SC Cell Biology GA DW3PU UT WOS:000383555300012 PM 27027731 ER PT S AU Krivega, I Dean, A AF Krivega, Ivan Dean, Ann GP New York Acad Sci TI Chromatin looping as a target for altering erythroid gene expression SO COOLEY'S ANEMIA SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 10th Cooley's Anemia Symposium CY OCT 18-22, 2015 CL Rosemont, IL SP ApoPharma, Acceleron, Celgene, Ionis Pharmaceut, Novartis, Immucor, Pfizer, Sangamo BioSciences DE thalassemia; fetal hemoglobin; globin switching; enhancer; chromatin looping ID BETA-GLOBIN LOCUS; BINDING PROTEIN LDB1; FETAL-HEMOGLOBIN; TRANSCRIPTION FACTORS; CHEMICAL PROBE; CONTROL REGION; POSITIVE ROLE; DIFFERENTIATION; ENHANCER; G9A AB The beta-hemoglobinopathies are the most common monogenic disorders in humans, with symptoms arising after birth when the fetal gamma-globin genes are silenced and the adult beta-globin gene is activated. There is a growing appreciation that genome organization and the folding of chromosomes are key determinants of gene transcription. Underlying this function is the activity of transcriptional enhancers that increase the transcription of target genes over long linear distances. To accomplish this, enhancers engage in close physical contact with target promoters through chromosome folding or looping that is orchestrated by protein complexes that bind to both sites and stabilize their interaction. We find that enhancer activity can be redirected with concomitant changes in gene transcription. Both targeting the beta-globin locus control region (LCR) to the gamma-globin gene in adult erythroid cells by tethering and epigenetic unmasking of a silenced gamma-globin gene lead to increased frequency of LCR/gamma-globin contacts and reduced LCR/gamma-globin contacts. The outcome of these manipulations is robust, pancellular gamma-globin transcription activation with a concomitant reduction in beta-globin transcription. These examples show that chromosome looping may be considered a therapeutic target for gene activation in beta-thalassemia and sickle cell disease. C1 [Krivega, Ivan; Dean, Ann] NIDDK, Lab Cellular & Dev Biol, NIH, 50 South Dr,MSC 8028, Bethesda, MD 20892 USA. RP Dean, A (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, 50 South Dr,MSC 8028, Bethesda, MD 20892 USA. EM anndean@helix.nih.gov FU Intramural NIH HHS [Z01 DK015508-20]; NIDDK NIH HHS [Z01 DK015508] NR 44 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2016 VL 1368 BP 31 EP 39 DI 10.1111/nyas.13012 PG 9 WC Hematology SC Hematology GA BF6WW UT WOS:000383744400005 PM 26918894 ER PT J AU Lee, DK Szabo, E AF Lee, Daniel K. Szabo, Eva TI Repurposing Drugs for Cancer Prevention SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE Aspirin; Cancer prevention; Metformin; Pioglitazone; Repurposing; Risk-benefit ID ACTIVATED RECEPTOR-GAMMA; TYPE-2 DIABETES-MELLITUS; CELL LUNG-CANCER; RANDOMIZED CONTROLLED-TRIALS; ABERRANT CRYPT FOCI; BREAST-CANCER; COLORECTAL-CANCER; METFORMIN PREVENTS; BLADDER-CANCER; COLON-CANCER AB Development of agents for cancer prevention has been particularly challenging for two main reasons. One is the inherent difficulty in identifying targets for the heterogeneous group of processes that lead to invasive cancer arising at different target organ sites, while the other is the need for safe, tolerable interventions that can be given for lengthy periods of time. The rapidly increasing understanding of the molecular pathogenesis of cancer is providing new opportunities for early intervention, prior to the development of invasive disease. Furthermore, there is an ever-increasing number of approved drugs with many different mechanisms of action. The appeal of using drugs with well described mechanisms of action and safety profiles has led to renewed interest in repurposing such agents for cancer prevention. Here we review the rationale and evidence of effectiveness of three agents that are the current focus of much interest in the field of cancer prevention - aspirin, metformin, and pioglitazone. C1 [Lee, Daniel K.] NCI, Ctr Canc Res, 9609 Med Ctr Dr,Room 5E-102, Bethesda, MD 20892 USA. [Szabo, Eva] NCI, Div Canc Prevent, 9609 Med Ctr Dr,Room 5E-102, Bethesda, MD 20892 USA. RP Szabo, E (reprint author), NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, NIH, 9609 Med Ctr Dr,Room 5E-102, Bethesda, MD 20892 USA. EM szaboe@mail.nih.gov NR 99 TC 0 Z9 0 U1 3 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-5294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2016 VL 16 IS 19 BP 2169 EP 2178 DI 10.2174/1568026616666160216154946 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA DZ0RJ UT WOS:000385547100010 PM 26881711 ER PT J AU Woodford, MR Dunn, DM Ciciarelli, JG Beebe, K Neckers, L Mollapour, M AF Woodford, Mark R. Dunn, Diana M. Ciciarelli, Joseph G. Beebe, Kristin Neckers, Len Mollapour, Mehdi TI Targeting Hsp90 in Non-Cancerous Maladies SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE Heat shock protein 90; Molecular Chaperones; Co-chaperone; Combination therapy; Hsp90; Pathogens; Post-translational modification ID SHOCK-PROTEIN 90; MOLECULAR CHAPERONE HSP90; PRIMARY EFFUSION LYMPHOMA; BREAST-CANCER CELLS; NF-KAPPA-B; ATP-BINDING; IN-VIVO; LEISHMANIA-DONOVANI; MULTIPLE-MYELOMA; DRUG-RESISTANCE AB Heat shock protein-90 (Hsp90) is a molecular chaperone critical to the folding, stability and activity of over 200 client proteins including many responsible for tumor initiation, progression and metastasis. Hsp90 chaperone function is linked to its ATPase activity and Hsp90 inhibitors interfere with this activity, thereby making Hsp90 an attractive target for cancer therapy. Also post-translational modification (PTM) and co-chaperone proteins modulate Hsp90 function, providing additional targets for secondary inhibition. Recent reports have shown that pathogens utilize both their own Hsp90 and that of their host for the propagation of infectious elements. In this review we will summarize our current knowledge of Hsp90 structure and function in both the pathogen and the host. We will focus on the role of Hsp90 in viral and parasitic diseases and the potential beneficial application of Hsp90 inhibitors alone and in combination with disease-specific inhibitors. C1 [Woodford, Mark R.; Dunn, Diana M.; Ciciarelli, Joseph G.; Mollapour, Mehdi] SUNY Upstate Med Univ, Dept Urol, 750 E Adams St, Syracuse, NY 13210 USA. [Woodford, Mark R.; Dunn, Diana M.; Ciciarelli, Joseph G.; Mollapour, Mehdi] SUNY Upstate Med Univ, Canc Res Inst, 750 E Adams St, Syracuse, NY 13210 USA. [Dunn, Diana M.; Ciciarelli, Joseph G.; Mollapour, Mehdi] SUNY Upstate Med Univ, Dept Biochem & Mol Biol, 750 E Adams St, Syracuse, NY 13210 USA. [Beebe, Kristin; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Mollapour, M (reprint author), SUNY Upstate Med Univ, Dept Urol, 750 E Adams St, Syracuse, NY 13210 USA.; Mollapour, M (reprint author), SUNY Upstate Med Univ, Canc Res Inst, 750 E Adams St, Syracuse, NY 13210 USA.; Mollapour, M (reprint author), SUNY Upstate Med Univ, Dept Biochem & Mol Biol, 750 E Adams St, Syracuse, NY 13210 USA. EM mollapom@upstate.edu FU SUNY Upstate Medical University; Carol M Baldwin Breast Cancer Fund of Central New York; One Square Mile of Hope Foundation FX We thank all our collaborators Chris Prodromou, Laurence H. Pearl, Cara Vaughan, Johannes Buchner, Matthias Mayer, Brian Blagg, William G. Stetler-Stevenson, Weiwen Ying, Tim Haystead and Andrew Truman for their scientific contributions. This work was supported with funds from SUNY Upstate Medical University, Carol M Baldwin Breast Cancer Fund of Central New York and One Square Mile of Hope Foundation (M.M.). NR 143 TC 0 Z9 0 U1 1 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-5294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2016 VL 16 IS 25 BP 2792 EP 2804 DI 10.2174/1568026616666160413141753 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA DZ0WD UT WOS:000385559500008 PM 27072697 ER PT S AU Mrabet, Y Kilicoglu, H Demner-Fushman, D AF Mrabet, Yassine Kilicoglu, Halil Demner-Fushman, Dina BE Kaminka, GA Fox, M Bouquet, P Hullermeier, E Dignum, V Dignum, F VanHarmelen, F TI Unsupervised Ranking of Knowledge Bases for Named Entity Recognition SO ECAI 2016: 22ND EUROPEAN CONFERENCE ON ARTIFICIAL INTELLIGENCE SE Frontiers in Artificial Intelligence and Applications LA English DT Proceedings Paper CT 22nd European Conference on Artificial Intelligence (ECAI) CY AUG 29-SEP 02, 2016 CL Hague, NETHERLANDS SP European Assoc Artificial Intelligence, PricewaterhouseCoopers, Taylor & Francis Grp, Essence ITN Network, Vrije Univ Amsterdam AB With the continuous growth of freely accessible knowledge bases and the heterogeneity of textual corpora, selecting the most adequate knowledge base for named entity recognition is becoming a challenge in itself. In this paper, we propose an unsupervised method to rank knowledge bases according to their adequacy for the recognition of named entities in a given corpus. Building on a state-of-the-art, unsupervised entity linking approach, we propose several evaluation metrics to measure the lexical and structural adequacy of a knowledge base for a given corpus. We study the correlation between these metrics and three standard performance measures: precision, recall and F1 score. Our multi-domain experiments on 9 different corpora with 6 knowledge bases show that three of the proposed metrics are strong performance predictors having 0.62 to 0.76 Pearson correlation with precision and 0.96 correlation with both recall and F1 score. C1 [Mrabet, Yassine; Kilicoglu, Halil; Demner-Fushman, Dina] Natl Lib Med, Bethesda, MD 20894 USA. [Mrabet, Yassine] CNRS, LORIA, F-75700 Paris, France. RP Mrabet, Y (reprint author), Natl Lib Med, Bethesda, MD 20894 USA.; Mrabet, Y (reprint author), CNRS, LORIA, F-75700 Paris, France. EM mrabety@mail.nih.gov; kilicogluh@mail.nih.gov; ddemner@mail.nih.gov NR 32 TC 0 Z9 0 U1 2 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6389 BN 978-1-61499-672-9; 978-1-61499-671-2 J9 FRONT ARTIF INTEL AP PY 2016 VL 285 BP 1248 EP 1255 DI 10.3233/978-1-61499-672-9-1248 PG 8 WC Computer Science, Artificial Intelligence SC Computer Science GA BF9PP UT WOS:000385793700145 ER PT J AU Kwon, HM Lynn, MJ Turan, TN Derdeyn, CP Fiorella, D Lane, BF Montgomery, J Janis, LS Rumboldt, Z Chimowitz, MI AF Kwon, Hyung-Min Lynn, Michael J. Turan, Tanya N. Derdeyn, Colin P. Fiorella, David Lane, Bethany F. Montgomery, Jean Janis, L. Scott Rumboldt, Zoran Chimowitz, Marc I. CA SAMMPRIS Investigators TI Frequency, Risk Factors, and Outcome of Coexistent Small Vessel Disease and Intracranial Arterial Stenosis Results From the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial SO JAMA NEUROLOGY LA English DT Article ID ISCHEMIC-STROKE; CEREBRAL MICROBLEEDS; LACUNAR INFARCTION; BRAIN INFARCTS; LEUKOARAIOSIS; ATHEROSCLEROSIS; HYPERINTENSITIES; ASSOCIATION; HEMORRHAGE; SEVERITY AB IMPORTANCE Intracranial arterial stenosis (ICAS) and small vessel disease (SVD) may coexist. There are limited data on the frequency and risk factors for coexistent SVD and the effect of SVD on stroke recurrence in patients receiving medical treatment for ICAS. OBJECTIVE To investigate the frequency and risk factors for SVD and the effect of SVD on stroke recurrence in patients with ICAS. DESIGN, SETTING, AND PARTICIPANTS A post hoc analysis of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study, a prospective, multicenter clinical trial. Among 451 participants, 313 (69.4%) had baseline brain magnetic resonance imaging scans read centrally for SVD that was defined by any of the following: old lacunar infarction, grade 2 to 3 on the Fazekas scale (for high-grade white matter hyperintensities), or microbleeds. Patient enrollment in SAMMPRIS began November 25, 2008, and follow-up ended on April 30, 2013. Data analysis for the present study was performed from May 13, 2014, to July 29, 2015. MAIN OUTCOMES AND MEASURES Risk factors in patients with vs without SVD and the association between SVD and other baseline risk factors with any ischemic stroke and ischemic stroke in the territory of the stenotic artery determined using proportional hazards regression. RESULTS Of 313 patients, 155 individuals (49.5%) had SVD noted on baseline magnetic resonance imaging. Variables that were significantly higher in patients with SVD, reported as mean (SD), included age, 63.5 (10.5) years (P <.001), systolic blood pressure, 149 (22) mm Hg (P <.001), glucose level, 130 (50) mg/dL (P =.03), and lower Montreal Cognitive Assessment scores (median, >= 24 [interquartile range, 20-26]; P =.02). Other significant variables were the number of patients with diabetes mellitus (88 of 155 [56.8%]; P =.003), coronary artery disease (46 [29.7%]; P =.004), stroke before the qualifying event (59 [38.1%]; P <.001), old infarct in the territory of the stenotic intracranial artery (88 [56.8%]; P <.001), and receiving antithrombotic therapy at the time of the qualifying event (109 [70.3%]; P =.005). The association between SVD and any ischemic stroke was nearly significant in the direction of a higher risk (18 [23.7%]); P =.07) for patients with SVD. On bivariate analysis, SVD was not associated with an increased risk on multivariable analyses (hazard ratio, 1.7 [95% CI, 0.8-3.8]; P =.20). In addition, SVD was not associated with an increased risk of stroke in the territory on either bivariate or multivariable analyses. CONCLUSIONS AND RELEVANCE Although SVD is common in patients with ICAS, the presence of SVD on baseline magnetic resonance imaging is not independently associated with an increased risk of stroke in patients with ICAS. C1 [Kwon, Hyung-Min] Seoul Natl Univ, Boramae Med Ctr, Dept Neurol, Seoul Metropolitan Govt, 20 Boramae Ro 5 Gil, Seoul 156707, South Korea. [Lynn, Michael J.; Montgomery, Jean] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinfomat, Atlanta, GA 30322 USA. [Turan, Tanya N.; Chimowitz, Marc I.] Med Univ South Carolina, Stroke Program, Dept Neurosci, Charleston, SC 29425 USA. [Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Neurol & Neurosurg, St Louis, MO USA. [Fiorella, David] SUNY Stony Brook, Dept Neurosurg, Stony Brook, NY 11794 USA. [Lane, Bethany F.] Morehouse Sch Med, Clin Res Ctr, Atlanta, GA 30310 USA. [Janis, L. Scott] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Rumboldt, Zoran] Med Univ South Carolina, Stroke Program, Dept Radiol, Charleston, SC 29425 USA. RP Kwon, HM (reprint author), Seoul Natl Univ, Boramae Med Ctr, Dept Neurol, Seoul Metropolitan Govt, 20 Boramae Ro 5 Gil, Seoul 156707, South Korea. EM hmkwon@snu.ac.kr OI Turan, Tanya/0000-0001-5399-8845; Derdeyn, Colin/0000-0002-5932-2683 FU US Public Health Service NINDS [U01 NS058728]; NIH; Medical University of South Carolina [UL1RR029882]; University of Florida [UL1RR029889]; University of Cincinnati [UL1RR029890]; University of California, San Francisco [UL1RR024131]; Stryker Neurovascular; Investigator-Sponsored Study Program of AstraZeneca FX This study was funded by research grant (U01 NS058728) from the US Public Health Service NINDS. In addition, the following Clinical and Translational Science Awards, funded by the NIH, provided local support for the evaluation of patients in the trial: UL1RR029882, Medical University of South Carolina; UL1RR029889, University of Florida; UL1RR029890, University of Cincinnati; and UL1RR024131, University of California, San Francisco. Corporate support was provided by Stryker Neurovascular (formerly Boston Scientific Neurovascular) for study devices and supplemental funding for third-party device distribution, site monitoring, and study auditing. This research was also supported by the Investigator-Sponsored Study Program of AstraZeneca, which donated rosuvastatin to study patients. INTERVENT provided the lifestyle modification program to the study at a discounted rate. The Regulatory and Clinical Research Institute (Minneapolis, Minnesota) provided assistance in designing the sitemonitoring processes and performing the sitemonitoring visits. The Veterans Affairs Cooperative Studies Program Clinical Research Pharmacy Coordinating Center (Albuquerque, New Mexico) handled the procurement, labeling, distribution, and inventory management of the study devices and rosuvastatin. Walgreens pharmacies provided study medications, except rosuvastatin, to patients at a discounted price (paid for by the study). NR 29 TC 4 Z9 4 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD JAN PY 2016 VL 73 IS 1 BP 36 EP 42 DI 10.1001/jamaneurol.2015.3145 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA DZ4RZ UT WOS:000385848500007 PM 26618534 ER PT J AU Estrada, LD Chamorro, D Yanez, MJ Gonzalez, M Leal, N von Bernhardi, R Dulcey, AE Marugan, J Ferrer, M Soto, C Zanlungo, S Inestrosa, NC Alvarez, AR AF Estrada, Lisbell D. Chamorro, David Jose Yanez, Maria Gonzalez, Marcelo Leal, Nancy von Bernhardi, Rommy Dulcey, Andres E. Marugan, Juan Ferrer, Marc Soto, Claudio Zanlungo, Silvana Inestrosa, Nibaldo C. Alvarez, Alejandra R. TI Reduction of Blood Amyloid-beta Oligomers in Alzheimer's Disease Transgenic Mice by c-Abl Kinase Inhibition SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid-beta peptide; amyloid-beta protein precursor; c-Abl tyrosine kinase; imatinib; oligomers; PMCA ID SECRETASE ACTIVATING PROTEIN; TYROSINE KINASE; CEREBROSPINAL-FLUID; PARKINSONS-DISEASE; IMATINIB MESYLATE; FAMILY KINASES; PHOSPHORYLATION; PEPTIDE; BRAIN; DEPOSITS AB One of the pathological hallmarks of Alzheimer's disease (AD) is the presence of amyloid plaques, which are deposits of misfolded and aggregated amyloid-beta peptide (A beta). The role of the c-Abl tyrosine kinase in A beta-mediated neurodegeneration has been previously reported. Here, we investigated the therapeutic potential of inhibiting c-Abl using imatinib. We developed a novel method, based on a technique used to detect prions (PMCA), to measure minute amounts of misfolded-A beta in the blood of AD transgenic mice. We found that imatinib reduces A beta-oligomers in plasma, which correlates with a reduction of AD brain features such as plaques and oligomers accumulation, neuroinflammation, and cognitive deficits. Cells exposed to imatinib and c-Abl KO mice display decreased levels of beta-CTF fragments, suggesting that an altered processing of the amyloid-beta protein precursor is the most probable mechanism behind imatinib effects. Our findings support the role of c-Abl in A beta accumulation and AD, and propose AD-PMCA as a new tool to evaluate AD progression and screening for drug candidates. C1 [Estrada, Lisbell D.; Chamorro, David; Jose Yanez, Maria; Gonzalez, Marcelo; Leal, Nancy; Alvarez, Alejandra R.] Pontificia Univ Catolica Chile, Fac Biol Sci, Dept Cell & Mol Biol, Cell Signaling Lab, Santiago, Region Metropol, Chile. [Estrada, Lisbell D.; Inestrosa, Nibaldo C.; Alvarez, Alejandra R.] Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Biol Celular, Ctr Envejecimiento & Regenerac CARE, Santiago, Region Metropol, Chile. [Estrada, Lisbell D.] Univ Bernardo O Higgins, Fac Salud, Lab Bionanotecnol, Santiago, Region Metropol, Chile. [von Bernhardi, Rommy] Pontificia Univ Catolica Chile, Sch Med, Dept Neurol, Santiago, Region Metropol, Chile. [Dulcey, Andres E.; Marugan, Juan; Ferrer, Marc] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA. [Soto, Claudio] Univ Texas Houston, Sch Med, Mitchell Ctr Alzheimers Dis & Related Brain Disor, Houston, TX USA. [Zanlungo, Silvana] Pontificia Univ Catolica Chile, Sch Med, Dept Gastroenterol, Santiago, Region Metropol, Chile. [Inestrosa, Nibaldo C.] Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia. [Inestrosa, Nibaldo C.] Univ Magallanes, Ctr Excelencia Biomed Magallanes CEBIMA, Punta Arenas, Chile. RP Alvarez, AR (reprint author), Pontificia Univ Catolica Chile, Portugal 49, Santiago 830025, Chile. EM aalvarez@bio.puc.cl FU FONDECYT [3110052, 11130561, 1120512, 1161065]; FONDEF [D10I1077]; CARE [CONICYT-PFB-12/2007] FX This work was supported by FONDECYT Postdoctoral Grant No 3110052 and FONDECYT Initiation into Research Grant No 11130561 to L.D.E. FONDEF Grant No D10I1077 and FONDECYT Grant No 1120512 and No 1161065 to A.R.A. Basal Funding CONICYT-PFB-12/2007 (CARE) to A.R.A. and N.I. NR 47 TC 0 Z9 0 U1 3 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2016 VL 54 IS 3 BP 1193 EP 1205 DI 10.3233/JAD-151087 PG 13 WC Neurosciences SC Neurosciences & Neurology GA DZ2DF UT WOS:000385651800031 PM 27567806 ER PT J AU Aas, S Wasserman, D AF Aas, Sean Wasserman, David TI Natural and Social Inequality Disability and Fair Equality of Opportunity SO JOURNAL OF MORAL PHILOSOPHY LA English DT Article DE social causation; disability; egalitarianism; equality of opportunity; responsibility ID JUSTICE AB This paper examines the moral import of a distinction between natural and social inequalities. Following Thomas Nagel, it argues for a "denatured" distinction that relies less on the biological vs. social causation of inequalities than on the idea that society is morally responsible for some inequalities but not others. It maintains that securing fair equality of opportunity by eliminating such social inequalities has particularly high priority in distributive justice. Departing from Nagel, it argues that society can be responsible for inequalities not only when they are the unintended result of justifiable projects, but even when their alleviation would be very costly. Sharing Nagel's general concept of 'social inequality, then, this paper proposes a far more expansive conception. We argue that many disadvantages due to disability fall under this conception. Eliminating or alleviating those disadvantages should be regarded as securing fair equality of opportunity, not improving the condition of the worst-off. C1 [Aas, Sean; Wasserman, David] NIH, Dept Clin Bioeth, Bldg 10, Bethesda, MD 20892 USA. RP Aas, S (reprint author), NIH, Dept Clin Bioeth, Bldg 10, Bethesda, MD 20892 USA. EM sean.aas@gmail.com; david.wasserman@nih.gov NR 31 TC 0 Z9 0 U1 0 U2 0 PU BRILL ACADEMIC PUBLISHERS PI LEIDEN PA PLANTIJNSTRAAT 2, P O BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 1740-4681 EI 1745-5243 J9 J MORAL PHILOS JI J. Moral Philos. PY 2016 VL 13 IS 5 BP 576 EP 601 DI 10.1163/17455243-46810042 PG 26 WC Ethics; Philosophy SC Social Sciences - Other Topics; Philosophy GA DY9SX UT WOS:000385476500004 ER PT S AU DePamphilis, ML AF DePamphilis, Melvin L. BE DePamphilis, ML TI CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY Mammalian Preimplantation Development PREFACE SO MAMMALIAN PREIMPLANTATION DEVELOPMENT SE Current Topics in Developmental Biology LA English DT Editorial Material; Book Chapter ID IMPLANTATION; FUTURE; MOUSE C1 [DePamphilis, Melvin L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. RP DePamphilis, ML (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 BN 978-0-12-801617-6; 978-0-12-801428-8 J9 CURR TOP DEV BIOL JI Curr. Top. Dev. Biol. PY 2016 VL 120 BP XIII EP XXI PG 9 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA BF6UG UT WOS:000383713000001 PM 27475860 ER PT S AU DePamphilis, ML AF DePamphilis, M. L. BE DePamphilis, ML TI Genome Duplication at the Beginning of Mammalian Development SO MAMMALIAN PREIMPLANTATION DEVELOPMENT SE Current Topics in Developmental Biology LA English DT Review; Book Chapter ID ORIGIN RECOGNITION COMPLEX; EUKARYOTIC DNA-REPLICATION; PREIMPLANTATION MOUSE EMBRYOS; MEIER-GORLIN SYNDROME; SPINDLE ASSEMBLY CHECKPOINT; BECKWITH-WIEDEMANN SYNDROME; ZYGOTIC GENE ACTIVATION; XENOPUS EGG EXTRACTS; INNER-CELL-MASS; RE-REPLICATION AB Nothing is more fundamental to mammalian development than the ability to accurately reproduce its genome once-but only once-each time a cell divides. In fact, the basic mechanism for replicating DNA has been conserved throughout evolution, even though the magnitude of the problem became monumental. A human cell contains 670 times the DNA in an E. coli cell, and human development requires trillions of cell divisions that produce about 37 billion miles of DNA! But instead of increasing the speed of replication forks to compensate for increasing genome size and organism complexity, evolution simply increased the number of replication origins. This allowed mammalian development regulate initiation of DNA replication during cell proliferation without interfering with the ever-changing demands of gene expression during cell differentiation. Moreover, it allowed developing tissues to complete genome duplication before beginning mitosis and to restrict genome duplication to once per cell division. And yet, to overproduce gene products during development, some cells are allowed to differentiate into nonproliferating polyploid cells. This chapter summarizes the mechanisms that make these events possible. Ironically, aberrations in these mechanisms are linked to cancer. In fact, the pluripotent cells produced during preimplantation development not only share characteristics of cancer cells, but they can also initiate cancer. C1 [DePamphilis, M. L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. RP DePamphilis, ML (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. EM depamphm@mail.nih.gov NR 176 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 BN 978-0-12-801617-6; 978-0-12-801428-8 J9 CURR TOP DEV BIOL JI Curr. Top. Dev. Biol. PY 2016 VL 120 BP 55 EP 102 DI 10.1016/bs.ctdb.2016.04.003 PG 48 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA BF6UG UT WOS:000383713000003 PM 27475849 ER PT J AU Sato, K Gorka, AP Nagaya, T Michie, MS Nakamura, Y Nani, RR Coble, VL Vasalatiy, OV Swenson, RE Choyke, PL Schnermann, MJ Kobayashi, H AF Sato, Kazuhide Gorka, Alexander P. Nagaya, Tadanobu Michie, Megan S. Nakamura, Yuko Nani, Roger R. Coble, Vince L. Vasalatiy, Olga V. Swenson, Rolf E. Choyke, Peter L. Schnermann, Martin J. Kobayashi, Hisataka TI Effect of charge localization on the in vivo optical imaging properties of near-infrared cyanine dye/monoclonal antibody conjugates SO MOLECULAR BIOSYSTEMS LA English DT Article ID GUIDED CANCER-SURGERY; MONOCLONAL-ANTIBODIES; FLUORESCENT PROTEINS; FLUOROPHORES; PHOTOIMMUNOTHERAPY; NAVIGATION AB Near-infrared (NIR) fluorophores show superior in vivo imaging properties than visible-light fluorophores because of the increased light penetration in tissue and lower autofluorescence of these wavelengths. We have recently reported that new NIR cyanine dyes containing a novel C4'-O-alkyl linker exhibit greater chemical stability and excellent optical properties relative to existing C4'-O-aryl variants. In this study, we synthesized two NIR cyanine dyes with the same core structure and charge but different indolenine substituents: FNIR-Z-759 bearing a combination of two sulfonates and two quaternary ammonium cations, and FNIR-G-765 bearing a combination of two sulfonates and two guanidines, resulting in zwitterionic charge with distinct cationic moieties. In this study, we compare the in vitro and in vivo optical imaging properties of monoclonal antibody (mAb) conjugates of FNIR-Z-759 and FNIR-G-765 with panitumumab (pan) at antibody-to-dye ratios of 1:2 or 1:5. One-to-five conjugation of pan-to-FNIR-G-765 was not successful due to aggregate formation during the conjugation reaction. Conjugates of both dyes to pan (2:1) demonstrated similar quenching capacity, stability, and brightness in target cells in vitro. However, FNIR-Z-759 conjugates showed significantly lower accumulation in the mouse liver, resulting in higher tumor-to-liver ratio. Thus, FNIR-Z-759 conjugates appear to have superior in vivo imaging characteristics compared with FNIR-G-765 conjugates, especially in the abdominal region. Moreover, from a chemistry point of view, mAb conjugation with FNIR-Z-759 has an advantage over FNIR-G-765, because it does not form aggregates at high dye-to-mAb ratio. These results suggest that zwitterionic cyanine dyes are a superior class of fluorophores for conjugating with mAbs for fluorescence imaging applications due to improving target-to-background contrast in vivo. However, zwitterionic cyanine dyes should be designed carefully, as small changes to the structure can alter in vivo pharmacokinetics of mAb-dye conjugates. C1 [Sato, Kazuhide; Nagaya, Tadanobu; Nakamura, Yuko; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA. [Gorka, Alexander P.; Michie, Megan S.; Nani, Roger R.; Schnermann, Martin J.] NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA. [Coble, Vince L.; Vasalatiy, Olga V.; Swenson, Rolf E.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA. [Schnermann, Martin J.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Bldg 376,Room 225D, Frederick, MD 21702 USA. [Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,RoomB3B69,MSC1088, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA.; Schnermann, MJ (reprint author), NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA.; Schnermann, MJ (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, NIH, Bldg 376,Room 225D, Frederick, MD 21702 USA.; Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,RoomB3B69,MSC1088, Bethesda, MD 20892 USA. EM martin.schnermann@nih.gov; kobayash@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. NR 25 TC 0 Z9 0 U1 5 U2 5 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X EI 1742-2051 J9 MOL BIOSYST JI Mol. Biosyst. PY 2016 VL 12 IS 10 BP 3046 EP 3056 DI 10.1039/c6mb00371k PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DX5FO UT WOS:000384405400010 PM 27452807 ER PT J AU Zhao, XL Parpart-Li, S Wang, XW AF Zhao, Xuelian Parpart-Li, Sonya Wang, Xin Wei TI The importance of integrated genomics to uncover clinically relevant cancer driver genes SO MOLECULAR & CELLULAR ONCOLOGY LA English DT Article ID PRINCIPLES AB Tumor heterogeneity hinders the discovery of true cancer driver genes. The recently identified role for YY1-associated protein 1 (YY1AP1) as a critical oncoprotein that is activated in a particular subtype of hepatocellular carcinoma (HCC) was elucidated through integrative genomic profiling followed by functional studies. This strategy proved effective for finding a functional cancer driver with prognostic impact. C1 [Zhao, Xuelian; Parpart-Li, Sonya; Wang, Xin Wei] NCI, Lab Human Carcinogenesis, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), NCI, Lab Human Carcinogenesis, Ctr Canc Res, Bethesda, MD 20892 USA. EM xw3u@nih.gov NR 10 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 2372-3556 EI 2372-3548 J9 MOL CELL ONCOL JI MOL. CELL ONCOL. PD JAN PY 2016 VL 3 IS 1 AR UNSP e1019975 DI 10.1080/23723556.2015.1019975 PG 3 WC Oncology SC Oncology GA DY6OD UT WOS:000385245700012 ER PT J AU Ciesla, L Moaddel, R AF Ciesla, Lukasz Moaddel, Ruin TI Comparison of analytical techniques for the identification of bioactive compounds from natural products SO NATURAL PRODUCT REPORTS LA English DT Review ID MEMBRANE AFFINITY-CHROMATOGRAPHY; COATED MAGNETIC BEADS; PERFORMANCE LIQUID-CHROMATOGRAPHY; OPEN-TUBULAR COLUMN; ULTRAFILTRATION-MASS-SPECTROMETRY; NICOTINIC ACETYLCHOLINE-RECEPTORS; GINGER ZINGIBER-OFFICINALE; IMMOBILIZED P-GLYCOPROTEIN; SOLID-PHASE EXTRACTION; HPLC-SPE-NMR AB Natural product extracts are a rich source of bioactive compounds. As a result, the screening of natural products for the identification of novel biologically active metabolites has been an essential part of several drug discovery programs. It is estimated that more than 70% of all drugs approved from 1981 and 2006, were either derived from or structurally similar to nature based compounds indicating the necessity for the development of a rapid method for the identification of novel compounds from plant extracts. The screening of biological matrices for the identification of novel modulators is nevertheless still challenging. In this review we discuss current techniques in phytochemical analysis and the identification of biologically active components. C1 [Ciesla, Lukasz; Moaddel, Ruin] NIA, Lab Clin Invest, Biomed Res Ctr, NIH, 8C232,251 Bayview Blvd, Baltimore, MD 21224 USA. [Ciesla, Lukasz] Med Univ Lublin, Dept Inorgan Chem, Chodzki 4A, PL-20093 Lublin, Poland. RP Moaddel, R (reprint author), NIA, Lab Clin Invest, Biomed Res Ctr, NIH, 8C232,251 Bayview Blvd, Baltimore, MD 21224 USA. EM moaddelru@mail.nih.gov FU NIA Intramural Research Program FX This work was supported by funds from the NIA Intramural Research Program. NR 94 TC 1 Z9 1 U1 20 U2 20 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0265-0568 EI 1460-4752 J9 NAT PROD REP JI Nat. Prod. Rep. PY 2016 VL 33 IS 10 BP 1131 EP 1145 DI 10.1039/c6np00016a PG 15 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA DY8EZ UT WOS:000385362900001 PM 27367973 ER PT S AU Deribe, K Tekola-Ayele, F Davey, G AF Deribe, Kebede Tekola-Ayele, Fasil Davey, Gail BE Gyapong, J Boatin, B TI Podoconiosis: Endemic Non-filarial Elephantiasis SO NEGLECTED TROPICAL DISEASES - SUB-SAHARAN AFRICA SE Neglected Tropical Diseases LA English DT Article; Book Chapter ID NEGLECTED TROPICAL DISEASE; NORTHERN ETHIOPIA; SOUTHERN ETHIOPIA; LOWER LEGS; NONFILARIAL ELEPHANTIASIS; WEST ETHIOPIA; WOLAITA ZONE; STIGMA; DISTRICT; PATHOGENESIS AB Podoconiosis is an endemic, non-filarial lymphoedema of the lower limb which needs to be differentiated from filarial elephantiasis, lymphoedema of systemic disease and leprotic lymphoedema. The disease (affecting genetically susceptible individuals who go barefoot) is linked to long-term exposure to red clay soil. Interactions between genetic and environmental factors trigger an inflammatory response that leads to lymphoedema and fibrosis. Patients with podoconiosis develop signs and symptoms in the second and third decades of life with the disease being common up to the sixth decade. The disease is bilateral but asymmetrical and almost always limited to below the knees. Globally, there are about four million people with podoconiosis, mainly in tropical Africa, central and South America and Southeast Asia. Tropical African countries bear the highest disease burden with about one million people living with podoconiosis in Ethiopia and a further 500,000 in Cameroon. The key strategies for podoconiosis control are prevention of contact with irritant soil (primary prevention) and lymphoedema morbidity management (secondary and tertiary prevention). The main challenge faced in podoconiosis is lack of awareness that the condition exists and that it is different from lymphatic filariasis and other main cause of lymphoedema in the tropics. This lack of awareness and diagnostic confusion with lymphatic filariasis has led to podoconiosis-affected communities being treated with DEC and albendazole. Research directed at the mapping of podoconiosis will have important consequences in planning the control and future elimination of the disease. Mapping of the disease burden of podoconiosis will help target resources, monitor control progress and advocate for investment in podoconiosis prevention, control and ultimately elimination. Mapping of disease must be accompanied by development of endemicity classifications and criteria for disease elimination before policies can be finalised. Controlling podoconiosis is achievable because no biological agent or vector involved in podoconiosis has been identified, the global scale of the problem is relatively small, the means for podoconiosis prevention and control are safe and additional strategies for prioritisation of resources such as the use of family health history and risk maps can be implemented. C1 [Deribe, Kebede; Davey, Gail] Univ Sussex, Brighton & Sussex Med Sch, Brighton BN1 9PX, E Sussex, England. [Tekola-Ayele, Fasil] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. RP Deribe, K (reprint author), Univ Sussex, Brighton & Sussex Med Sch, Brighton BN1 9PX, E Sussex, England. EM kebededeka@yahoo.com NR 51 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 2194-8275 BN 978-3-319-25471-5; 978-3-319-25469-2 J9 NEGLECT TROP DIS PY 2016 BP 231 EP 249 DI 10.1007/978-3-319-25471-5_10 D2 10.1007/978-3-319-25471-5 PG 19 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA BF9LG UT WOS:000385737100012 ER PT J AU Ferreira, M Firmino-Machado, J Marques, EA Santos, PC Simoes, AD Duarte, JA AF Ferreira, Margarida Firmino-Machado, Joao Marques, Elisa A. Santos, Paula C. Simoes, Ana Daniela Duarte, Jose A. TI Prognostic factors for recovery in Portuguese patients with Bell's palsy SO NEUROLOGICAL RESEARCH LA English DT Article DE Facial palsy; Prognostic factors; House-Brackmann Facial Grading System measure ID HERPES-SIMPLEX; FACIAL PARALYSIS; MANAGEMENT; THERAPY AB Objective: The main aim of this study was to identify the prognostic factors that contribute to complete recovery at 6 weeks and 6 months in patients with Bell's palsy. Material and Methods: This is a prospective, longitudinal, and descriptive study that included 123 patients diagnosed with facial nerve palsy (FNP) at a hospital in Guimaraes, Portugal. However, only 73 patients with Bell's palsy (BP) were included in the assessment of recovery at 6 weeks and 6 months. We analyzed the demographic and clinical characteristics of the patients, including sex, age, paralyzed side, occupation, previous and associated symptoms, seasonal occurrence, familial facial palsy, patient perception, intervention options, and baseline grade according to the House-Brackmann facial grading system (HB-FGS). Results: Of the 123 cases with FNP, 79 (64.2%) patients had BP. Age, sex, and baseline HB-FGS grades were significant predictors of complete recovery at 6 weeks. Patients with HB-FGS grade III or lower (6 weeks baseline) had significant recovery of function at 6 months. Conclusions: Baseline severity of BP, elderly patients, and male sex were early predictors of poor prognosis. Patients with mild and moderate dysfunction according to the HB-FGS achieved significant normal facial function at 6 months. Further prospective studies with longer observation periods and larger samples are needed to verify the results. C1 [Ferreira, Margarida; Santos, Paula C.; Duarte, Jose A.] Univ Porto, Res Ctr Phys Act Hlth & Leisure, Fac Sport, Oporto, Portugal. [Ferreira, Margarida; Simoes, Ana Daniela] North Polytech Inst Hlth, CESPU, Dept Physiotherapy, Gandra, Portugal. [Ferreira, Margarida; Simoes, Ana Daniela] North Polytech Inst Hlth, CESPU, Dept Physiotherapy, Vila Nova De Famalicao, Portugal. [Firmino-Machado, Joao] Dept Publ Hlth Occidental Oporto, Oporto, Portugal. [Marques, Elisa A.] Univ Inst Maia ISMAI, Res Ctr Sports Sci Hlth & Human Dev CIDESD, Maia, Portugal. [Marques, Elisa A.] NIA, NIH, Bethesda, MD 20892 USA. [Santos, Paula C.] Polytech Inst Porto, Sch Hlth Technol Porto, Dept Phys Therapy, Vila Nova De Gaia, Portugal. RP Ferreira, M (reprint author), Ctr Hosp Alto Ave, Rua Cutileiros, P-4835044 Creixomil, Guimaraes, Portugal. EM margarida.ferreira@ipsn.cespu.pt OI Simoes, Daniela/0000-0003-2034-5105 NR 31 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0161-6412 EI 1743-1328 J9 NEUROL RES JI Neurol. Res. PY 2016 VL 38 IS 10 BP 851 EP 856 DI 10.1080/01616412.2016.1209620 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DX3PP UT WOS:000384285300001 PM 27426639 ER PT J AU Crompton, JG Sukumar, M Restifo, NP AF Crompton, Joseph G. Sukumar, Madhusudhanan Restifo, Nicholas P. TI Targeting Akt in cell transfer immunotherapy for cancer SO ONCOIMMUNOLOGY LA English DT Article DE Akt inhibition; cell-based immunotherapy; immunometabolism ID ADOPTIVE IMMUNOTHERAPY; IMMUNE CELLS; INHIBITION; TUMORS AB Pharmacologic inhibitors of the serine/threonine kinase Akt, initially aimed at deranged oncogenic pathways in tumors, have recently been shown to act as immunomodulators that markedly enhance the antitumor properties of T cells. Repurposing Akt inhibitors to improve antitumor immunity may be viewed as a manifestation of a larger paradigmatic shift in which hallmark characteristics of cancer (e.g., immune evasion), rather than merely causal features (e.g., somatic mutations) can be exploited for therapeutic benefit. C1 [Crompton, Joseph G.; Sukumar, Madhusudhanan; Restifo, Nicholas P.] NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Crompton, Joseph G.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. RP Restifo, NP (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM restifo@nih.gov NR 10 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 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 9 AR e1014776 DI 10.1080/2162402X.2015.1014776 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA DZ0KR UT WOS:000385528200001 PM 27757294 ER PT J AU Granzin, M Stojanovic, A Miller, M Childs, R Huppert, V Cerwenka, A AF Granzin, Markus Stojanovic, Ana Miller, Matthias Childs, Richard Huppert, Volker Cerwenka, Adelheid TI Highly efficient IL-21 and feeder cell-driven ex vivo expansion of human NK cells with therapeutic activity in a xenograft mouse model of melanoma SO ONCOIMMUNOLOGY LA English DT Article DE Cancer immunotherapy; EBV-LCL; Interleukin-21; melanoma; Natural killer cells; NK cell expansion; xenograft mouse model ID NATURAL-KILLER-CELLS; IN-VIVO; LINE NK-92; CANCER; IMMUNOTHERAPY; TRANSPLANTATION; INTERLEUKIN-21; ACTIVATION; IMMUNITY; RECEPTOR AB Natural killer (NK) cells are promising antitumor effector cells, but the generation of sufficient NK cell numbers for adoptive immunotherapy remains challenging. Therefore, we developed a method for highly efficient ex vivo expansion of human NK cells.Ex vivo expansion of NK cells in medium containing IL-2 and irradiated clinical-grade feeder cells (EBV-LCL) induced a 22-fold NK cell expansion after one week that was significantly increased to 53-fold by IL-21. Repeated stimulation with irradiated EBV-LCL and IL-2 and addition of IL-21 at the initiation of the culture allowed sustained NK cell proliferation with 10(11)-fold NK cell expansion after 6 weeks. Compared to naive NK cells, expanded NK cells upregulated TRAIL, NKG2D, and DNAM-1, had superior cytotoxicity against tumor cell lines in vitro and produced more IFN and TNF- upon PMA/Iono stimulation. Most importantly, adoptive transfer of NK cells expanded using feeder cells, IL-2 and IL-21 led to significant inhibition of tumor growth in a melanoma xenograft mouse model, which was greater than with NK cells activated with IL-2 alone. Intriguingly, adoptively transferred NK cells maintained their enhanced production of IFN and TNF- upon ex vivo restimulation, although they rapidly lost their capacity to degranulate and mediate tumor cytotoxicity after the in vivo transfer.In conclusion, we developed a protocol for ex vivo NK cell expansion that results in outstanding cell yields. The expanded NK cells possess potent antitumor activity in vitro and in vivo and could be utilized at high numbers for adoptive immunotherapy in the clinic. C1 [Granzin, Markus; Stojanovic, Ana; Miller, Matthias; Cerwenka, Adelheid] German Canc Res Ctr, Innate Immun Grp, Heidelberg, Germany. [Granzin, Markus; Huppert, Volker] Miltenyi Biotec GmbH, Bergisch Gladbach, Germany. [Childs, Richard] NHLBI, Sect Transplantat Immunotherapy, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Granzin, M; Cerwenka, A (reprint author), German Canc Res Ctr, Innate Immun Grp, Heidelberg, Germany.; Granzin, M (reprint author), Miltenyi Biotec GmbH, Bergisch Gladbach, Germany. EM markusgr@miltenyibiotec.de; A.Cerwenka@dkfz-heidelberg.de NR 34 TC 0 Z9 0 U1 6 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 9 AR e1219007 DI 10.1080/2162402X.2016.1219007 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA DZ0KR UT WOS:000385528200024 PM 27757317 ER PT J AU Roselli, M Formica, V Cereda, V Jochems, C Richards, J Grenga, I Orlandi, A Ferroni, P Guadagni, F Schlom, J AF Roselli, Mario Formica, Vincenzo Cereda, Vittore Jochems, Caroline Richards, Jacob Grenga, Italia Orlandi, Augusto Ferroni, Patrizia Guadagni, Fiorella Schlom, Jeffrey TI The association of clinical outcome and peripheral T-cell subsets in metastatic colorectal cancer patients receiving first-line FOLFIRI plus bevacizumab therapy SO ONCOIMMUNOLOGY LA English DT Article DE Chemotherapy; colorectal cancer; FOLFIRI; immunotherapy; peripheral T cells; Tregs ID MICROSATELLITE INSTABILITY; COLON-CANCER; CARCINOMA PATIENTS; SUNITINIB; VACCINE; SURVIVAL; CRITERIA; CHEMOTHERAPY; COMBINATION; SUPPRESSION AB The first-line standard of care for patients with metastatic colorectal cancer (mCRC) is FOLFIRI (irinotecan, levo-leucovorin, 5-fluorouracil (5-FU)) plus bevacizumab. With the renewed interest in cancer immunotherapy with agents such as vaccines, checkpoint inhibitors and immune modulators, the possibility exists for the use of one or more of these immunotherapeutics in the first-line setting and thus in combination with the FOLFIRI and bevacizumab regimen. Studies were undertaken to study the effects of FOLFIRI and bevacizumab therapy on peripheral T-cell subsets, and to determine if there are any associations between these subsets and response to therapy. Peripheral blood mononuclear cell subsets of patients with mCRC (n = 23) were analyzed prior to and during therapy. While there were differences among patients, the majority of patients showed either a minimal change or an increase in CD4(+) T cell to regulatory T cell (Treg) ratios during therapy, as well as either minimal change or a decrease in Treg suppressive activity during therapy. There was also an association (p = 0.036) between a decrease in Treg frequency during FOLFIRI therapy and overall survival, and an association (p = 0.037) between the frequency of Tregs prior to therapy and progression-free survival. Responders to the chemotherapy by RECIST criteria also had a greater decrease in Tregs during therapy vs. pre-therapy (p = 0.0064) as compared to non-responders. While the number of mCRC patients undergoing chemotherapy in this study is relatively small, it provides the rationale for the use of immunotherapeutics in this first-line metastatic setting. C1 [Roselli, Mario; Formica, Vincenzo; Cereda, Vittore] Univ Roma Tor Vergata, Tor Vergata Univ, Clin Ctr, Med Oncol,Dept Syst Med, Rome, Italy. [Jochems, Caroline; Richards, Jacob; Grenga, Italia; Schlom, Jeffrey] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. [Orlandi, Augusto] Univ Roma Tor Vergata, Anat Pathol Inst, Dept Biomed & Prevent, Rome, Italy. [Ferroni, Patrizia; Guadagni, Fiorella] San Raffaele Roma Open Univ, Dept Human Sci & Qual Life Promot, Rome, Italy. [Guadagni, Fiorella] IRCCS San Raffaele Pisana, Interinst Multidisciplinary Biobank BioBIM, Rome, Italy. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Ferroni, Patrizia/C-2705-2017 OI Ferroni, Patrizia/0000-0002-9877-8712 FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. This work has been partially carried out within the Ph.D. program in "Medicina Sperimentale e dei Sistemi" XXXI Ciclo, Tor Vergata University, Rome, Italy. NR 25 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 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 7 AR e1188243 DI 10.1080/2162402X.2016.1188243 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA DY9WR UT WOS:000385486700032 ER PT J AU Wood, LV Fojo, A Roberson, BD Hughes, MSB Dahut, W Gulley, JL Madan, RA Arlen, PM Sabatino, M Stroncek, DF Castiello, L Trepel, JB Lee, MJ Parnes, HL Steinberg, SM Terabe, M Wilkerson, J Pastan, I Berzofsky, JA AF Wood, Lauren V. Fojo, Antonio Roberson, Brenda D. Hughes, Meghan S. B. Dahut, William Gulley, James L. Madan, Ravi A. Arlen, Philip M. Sabatino, Marianna Stroncek, David F. Castiello, Luciano Trepel, Jane B. Lee, Min-Jung Parnes, Howard L. Steinberg, Seth M. Terabe, Masaki Wilkerson, Julia Pastan, Ira Berzofsky, Jay A. TI TARP vaccination is associated with slowing in PSA velocity and decreasing tumor growth rates in patients with Stage D0 prostate cancer SO ONCOIMMUNOLOGY LA English DT Article DE Prostate cancer; PSA biochemical recurrence; TARP; therapeutic cancer vaccine ID ANTIGEN DOUBLING TIME; ALTERNATE READING FRAME; RADICAL PROSTATECTOMY; BREAST-CANCER; CELLULAR IMMUNOTHERAPY; RADIATION-THERAPY; GM-CSF; CELLS; PROTEIN; SURVIVAL AB T-cell receptor alternate reading frame protein (TARP) is a 58-residue protein over-expressed in prostate and breast cancer. We investigated TARP peptide vaccination's impact on the rise in PSA (expressed as Slope Log(PSA) or PSA Doubling Time (PSADT)), validated tumor growth measures, and tumor growth rate in men with Stage D0 prostate cancer. HLA-A*0201 positive men were randomized to receive epitope-enhanced (29-37-9V) and wild-type (27-35) TARP peptides administered as a Montanide/GM-CSF peptide emulsion or as an autologous peptide-pulsed dendritic cell vaccine every 3 weeks for a total of five vaccinations with an optional 6th dose of vaccine at 36 weeks based on immune response or PSADT criteria with a booster dose of vaccine for all patients at 48 and 96 weeks. 41 patients enrolled with median on-study duration of 75 weeks at the time of this analysis. Seventy-two percent of patients reaching 24 weeks and 74% reaching 48 weeks had a decreased Slope Log(PSA) compared to their pre-vaccination baseline (p = 0.0012 and p = 0.0004 for comparison of overall changes in Slope Log(PSA), respectively). TARP vaccination also resulted in a 50% decrease in median tumor growth rate (g): pre-vaccine g = 0.0042/day, post-vaccine g = 0.0021/day (p = 0.003). 80% of subjects exhibited new vaccine-induced TARP-specific IFN gamma ELISPOT responses but they did not correlate with decreases in Slope Log (PSA). Thus, vaccination with TARP peptides resulted in significant slowing in PSA velocity and reduction in tumor growth rate in a majority of patients with PSA biochemical recurrence. C1 [Wood, Lauren V.; Roberson, Brenda D.; Hughes, Meghan S. B.; Terabe, Masaki; Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, Bldg 10,Room 4A22,10 Ctr Dr,MSC 1578, Bethesda, MD 20892 USA. [Fojo, Antonio; Dahut, William; Gulley, James L.; Madan, Ravi A.; Arlen, Philip M.; Wilkerson, Julia] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Sabatino, Marianna; Stroncek, David F.; Castiello, Luciano] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Trepel, Jane B.; Lee, Min-Jung] NCI, Dev Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Parnes, Howard L.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Pastan, Ira] Ctr Canc Res, Mol Biol Lab, NCI, Bethesda, MD USA. RP Wood, LV (reprint author), NCI, Vaccine Branch, Ctr Canc Res, Bldg 10,Room 4A22,10 Ctr Dr,MSC 1578, Bethesda, MD 20892 USA. EM woodl@mail.nih.gov OI Wilkerson, Julia/0000-0002-6965-0867 FU NCI Intramural Research Program FX This work was supported by the NCI Intramural Research Program. NR 43 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 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 8 AR e1197459 DI 10.1080/2162402X.2016.1197459 PG 13 WC Oncology; Immunology SC Oncology; Immunology GA DZ0IW UT WOS:000385522800019 PM 27622067 ER PT B AU Georgiev, GY Gombos, E Bates, T Henry, K Casey, A Daly, M AF Georgiev, Georgi Yordanov Gombos, Erin Bates, Timothy Henry, Kaitlin Casey, Alexander Daly, Michael BE Battiston, S DePellegrini, F Caldarelli, G Merelli, E TI Free Energy Rate Density and Self-organization in Complex Systems SO PROCEEDINGS OF ECCS 2014: EUROPEAN CONFERENCE ON COMPLEX SYSTEMS SE Springer Proceedings in Complexity LA English DT Proceedings Paper CT European Conference on Complex Systems (ECCS) CY SEP 22-26, 2014 CL IMT Sch Adv Studies Lucca, Lucca, ITALY SP Complex Sys Soc HO IMT Sch Adv Studies Lucca ID IRREVERSIBLE-PROCESSES AB One of the most important tasks in science is to understand the self-organization's arrow of time. To attempt this we utilize the connection between self-organization and non-equilibrium thermodynamics. Eric Chaisson calculated an exponential increase of Free Energy Rate Density (FERD) inCosmic Evolution, from the Big Bang until now, paralleling the increase of systems' structure. We term these studies "Devology". We connect the exponential growth of FERD to the principle of least action for complex systems leading to exponential increase of action efficiency. We study CPUs as a specific system in which the organization, the total amount of action and FERD are connected in a positive feedback loop, providing exponential growth of all three and power law relations between them. This is a deep connection, reaching to the first principles of physics: the least action principle and the second law of thermodynamics. We propose size-density and complexity-density rules in addition to the established size-complexity one. C1 [Georgiev, Georgi Yordanov; Gombos, Erin; Bates, Timothy; Henry, Kaitlin; Casey, Alexander; Daly, Michael] Assumption Coll, Dept Phys, 500 Salisbury St, Worcester, MA 01609 USA. [Georgiev, Georgi Yordanov] Tufts Univ, Dept Phys, 4 Colby St, Medford, MA 02155 USA. [Georgiev, Georgi Yordanov] Worcester Polytech Inst, Dept Phys, Worcester, MA 01609 USA. [Gombos, Erin] NCI, NIH, 10 Ctr Dr, Bethesda, MD 20814 USA. [Casey, Alexander] Univ Notre Dame, Notre Dame, IN 46556 USA. [Daly, Michael] Meditech, 550 Cochituate Rd, Framingham, MA 01701 USA. RP Georgiev, GY (reprint author), Assumption Coll, Dept Phys, 500 Salisbury St, Worcester, MA 01609 USA. EM ggeorgie@assumption.edu NR 16 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-3-319-29228-1; 978-3-319-29226-7 J9 SPRINGER PR COMPLEX PY 2016 BP 321 EP 327 DI 10.1007/978-3-319-29228-1_27 PG 7 WC Computer Science, Theory & Methods; Mathematics, Applied SC Computer Science; Mathematics GA BF8XR UT WOS:000385253000027 ER PT S AU Hegyi, P Wilschanski, M Muallem, S Lukacs, GL Sahin-Toth, M Uc, A Gray, MA Rakonczay, Z Maleth, J AF Hegyi, Peter Wilschanski, Michael Muallem, Shmuel Lukacs, Gergely L. Sahin-Toth, Miklos Uc, Aliye Gray, Michael A. Rakonczay, Zoltan, Jr. Maleth, Jozsef BE Nilius, B DeTombe, P Gudermann, T Jahn, R Lill, R Petersen, O TI CFTR: A New Horizon in the Pathomechanism and Treatment of Pancreatitis SO REVIEWS OF PHYSIOLOGY, BIOCHEMISTRY AND PHARMACOLOGY, VOL 170 SE Reviews of Physiology Biochemistry and Pharmacology LA English DT Review; Book Chapter DE CFTR; Cystic fibrosis; Epithelial transport; Pancreas; Pancreatitis ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS GENE; POTENTIAL DIFFERENCE MEASUREMENTS; IDIOPATHIC CHRONIC-PANCREATITIS; PREMATURE STOP MUTATIONS; CIGARETTE-SMOKE; DUCT CELLS; IN-VITRO; AMINOGLYCOSIDE ANTIBIOTICS; ENDOPLASMIC-RETICULUM AB Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel that conducts chloride and bicarbonate ions across epithelial cell membranes. Mutations in the CFTR gene diminish the ion channel function and lead to impaired epithelial fluid transport in multiple organs such as the lung and the pancreas resulting in cystic fibrosis. Heterozygous carriers of CFTR mutations do not develop cystic fibrosis but exhibit increased risk for pancreatitis and associated pancreatic damage characterized by elevated mucus levels, fibrosis, and cyst formation. Importantly, recent studies demonstrated that pancreatitis causing insults, such as alcohol, smoking, or bile acids, strongly inhibit CFTR function. Furthermore, human studies showed reduced levels of CFTR expression and function in all forms of pancreatitis. These findings indicate that impairment of CFTR is critical in the development of pancreatitis; therefore, correcting CFTR function could be the first specific therapy in pancreatitis. In this review, we summarize recent advances in the field and discuss new possibilities for the treatment of pancreatitis. C1 [Hegyi, Peter] Univ Pecs, Inst Translat Med, Pecs, Hungary. [Hegyi, Peter] Univ Pecs, Dept Med 1, Pecs, Hungary. [Hegyi, Peter; Maleth, Jozsef] MTA SZTE Translat Gastroenterol Res Grp, Szeged, Hungary. [Hegyi, Peter; Rakonczay, Zoltan, Jr.; Maleth, Jozsef] Univ Szeged, Dept Med 1, Szeged, Hungary. [Wilschanski, Michael] Hebrew Univ Jerusalem, Pediat Gastroenterol Unit, Hadassah Med Ctr, Jerusalem, Israel. [Muallem, Shmuel] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. [Lukacs, Gergely L.] McGill Univ, Dept Physiol, Montreal, PQ, Canada. [Sahin-Toth, Miklos] Boston Univ, Dept Mol & Cell Biol, Henry M Goldman Sch Dent Med, Boston, MA 02215 USA. [Uc, Aliye] Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA. [Gray, Michael A.] Newcastle Univ, Univ Med Sch, Inst Cell & Mol Biosci, Newcastle Upon Tyne, Tyne & Wear, England. [Rakonczay, Zoltan, Jr.] Univ Szeged, Dept Pathophysiol, Szeged, Hungary. RP Hegyi, P (reprint author), Univ Pecs, Inst Translat Med, Pecs, Hungary.; Hegyi, P (reprint author), Univ Pecs, Dept Med 1, Pecs, Hungary. EM hegyi.peter@med.u-szeged.hu OI Lukacs, Gergely/0000-0003-0900-0675 FU NIDCR NIH HHS [ZIA DE000735]; NIDDK NIH HHS [R01 DK075302, P30 DK054759, R01 DK058088, R01 DK097820, R21 DK096327, R24 DK096518] NR 115 TC 4 Z9 4 U1 8 U2 9 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0303-4240 BN 978-3-319-31492-1; 978-3-319-31491-4 J9 REV PHYSIOL BIOCH P JI Rev. Physiol. Biochem. Pharmacol. PY 2016 VL 170 BP 37 EP 66 DI 10.1007/112_2015_5002 D2 10.1007/978-3-319-31492-1 PG 30 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Physiology GA BF8ZJ UT WOS:000385353400002 PM 26856995 ER PT J AU Simons-Morton, BG Li, KG Ehsani, J Ouimet, MC Perlus, J Klauer, SG AF Simons-Morton, Bruce G. Li, Kaigang Ehsani, Johnathon Ouimet, Marie Claude Perlus, Jessamyn Klauer, Sheila G. TI Are Perceptions About Driving Risk and Driving Skill Prospectively Associated with Risky Driving Among Teenagers? SO TRANSPORTATION RESEARCH RECORD LA English DT Article ID YOUNG DRIVERS; NOVICE TEENAGERS; SELF-ASSESSMENT; PERCEIVED RISK; BEHAVIOR; CRASHES; PREDICTORS; PASSENGERS; ATTITUDES; ADOLESCENTS AB The objective of this study was to examine prospective associations of perceptions of driving risk and skill with teenage risky driving. The vehicles of 42 newly licensed teenage drivers were instrumented with a data acquisition system. Objective measures of risky driving [crash and near crash (CNC) and kinematic risky driving (KRD) rates] obtained from accelerometers were aggregated over three 6-month periods (T1, T2, and T3). The Checkpoints Self-Reported Risky Driving Scale (C-RDS) and perceptions of driving risk and driving skills were collected at corresponding 6-month intervals. The results indicated that CNC, KRD, and C-RDS were significantly correlated at T1 to T3. Perceptions of driving risk and skill were not significantly correlated with objective or self-reported measures of risky driving. No evidence was found that perceptions of risk or skill were prospectively associated with risky driving. It was concluded that perceptions of risk and driving skills may have limited utility as objectives of prevention efforts. C1 [Simons-Morton, Bruce G.; Li, Kaigang; Ehsani, Johnathon; Perlus, Jessamyn] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd, North Bethesda, MD 20892 USA. [Ouimet, Marie Claude] Univ Sherbrooke, Fac Med & Hlth Sci, 150 Charles Le Moyne Pl,Suite 200, Longueuil, PQ J4K 0A8, Canada. [Klauer, Sheila G.] Virginia Polytech Inst & State Univ, Virginia Tech Transportat Inst, 3500 Transportat Res Plaza, Blacksburg, VA 24061 USA. RP Simons-Morton, BG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd, North Bethesda, MD 20892 USA. EM mortonb@mail.nih.gov FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 46 TC 0 Z9 0 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0361-1981 EI 2169-4052 J9 TRANSPORT RES REC JI Transp. Res. Record PY 2016 IS 2584 BP 39 EP 44 DI 10.3141/2584-06 PG 6 WC Engineering, Civil; Transportation; Transportation Science & Technology SC Engineering; Transportation GA DZ2SZ UT WOS:000385693100007 ER PT J AU Wright, N Walters, P Strang, J AF Wright, Nat Walters, Pamela Strang, John TI Dual diagnosis in prisons: management of co-existing substance use and mental health disorders Prevalence of mental ill health in prisons SO ADVANCES IN DUAL DIAGNOSIS LA English DT Editorial Material ID PSYCHIATRIC-DISORDERS; OUTCOMES; SUICIDE; ENGLAND; COHORT; WALES; RISK; TC C1 [Walters, Pamela] SWL & St Georges Mental Hlth Trust, London, England. [Walters, Pamela] South London & Maudsley Mental Hlth NHS Trust, London, England. [Strang, John] Kings Coll London, IoPPN, Dept Addict Acad Act, London WC2R 2LS, England. [Strang, John] KHP AHSC Kings Hlth Partners Acad Hlth Sci Ctr, CAG, London, England. [Strang, John] South London & Maudsley SLaM NHS Fdn Trust, London, England. [Strang, John] Kings Coll London, London WC2R 2LS, England. [Strang, John] WHO, Geneva, Switzerland. [Strang, John] UNODC, Vienna, Austria. [Strang, John] US FDA, EMCDDA, Rockville, MD 20857 USA. [Strang, John] NIDA, Bethesda, MD USA. RP Walters, P (reprint author), SWL & St Georges Mental Hlth Trust, London, England.; Walters, P (reprint author), South London & Maudsley Mental Hlth NHS Trust, London, England. EM nat.wright@spectrum-cic.nhs.uk NR 32 TC 0 Z9 0 U1 1 U2 1 PU EMERALD GROUP PUBLISHING LTD PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY BD16 1WA, W YORKSHIRE, ENGLAND SN 1757-0972 EI 2042-8324 J9 ADV DUAL DIAGN JI Adv. Dual Diagn. PY 2016 VL 9 IS 1 BP 1 EP 6 DI 10.1108/ADD-12-2015-0025 PG 6 WC Psychology, Clinical SC Psychology GA DY0NW UT WOS:000384794500001 ER PT J AU Rajan, A Kim, C Heery, CR Guha, U Gulley, JL AF Rajan, Arun Kim, Chul Heery, Christopher R. Guha, Udayan Gulley, James L. TI Nivolumab, anti-programmed death-1 (PD-1) monoclonal antibody immunotherapy: Role in advanced cancers SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Review DE immunotherapy; immune checkpoint inhibitors; melanoma; nivolumab; non-small cell lung cancer; renal cell carcinoma ID RENAL-CELL CARCINOMA; PHASE-III TRIAL; LUNG-CANCER; METASTATIC MELANOMA; UNTREATED MELANOMA; ANTI-PD-1 ANTIBODY; OPEN-LABEL; TUMOR MICROENVIRONMENT; IMMUNE CHECKPOINTS; ANTITUMOR IMMUNITY AB The development of immune checkpoint inhibitors has altered the landscape of treatment of advanced cancers. These drugs are well tolerated and have shown clinical activity against a wide variety of solid tumors and hematological malignancies. The durability of response is particularly impressive when compared to other forms of systemic therapy. Nivolumab (Opdivo) is an IgG4 antibody that causes immune checkpoint blockade by diminishing inhibitory signaling through the programmed death receptor-1 pathway. It is approved for treatment of recurrent non-small cell lung cancer, melanoma, and renal cell carcinoma. Efforts to identify biomarkers of response to nivolumab are ongoing. Clinical trials are also being conducted to determine the benefits of combining nivolumab with other forms of treatment including chemotherapy, molecular-targeted therapy, radiation therapy, and other forms of immune therapy. This review outlines the clinical trials that have led to the emergence of nivolumab as a treatment option for patients with advanced cancers. C1 [Rajan, Arun; Kim, Chul; Guha, Udayan] NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Heery, Christopher R.; Gulley, James L.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. [Gulley, James L.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Rajan, A (reprint author), NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.; Rajan, A (reprint author), NCI, Thorac & GI Oncol Branch, NIH, 10 CRC,Room 4-5330, Bethesda, MD 20892 USA. EM rajana@mail.nih.gov FU Intramural Research Program, Center for Cancer Research, National Cancer Institute/National Institutes of Health FX The authors wish to acknowledge the support of the Intramural Research Program, Center for Cancer Research, National Cancer Institute/National Institutes of Health in the preparation of this manuscript. NR 88 TC 3 Z9 3 U1 5 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PY 2016 VL 12 IS 9 BP 2219 EP 2231 DI 10.1080/21645515.2016.1175694 PG 13 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA DX2RA UT WOS:000384217200014 PM 27135835 ER PT J AU Abrams, LR Koehly, LM Hooker, GW Paquin, RS Capella, JN McBride, CM AF Abrams, Leah R. Koehly, Laura M. Hooker, Gillian W. Paquin, Ryan S. Capella, Joseph N. McBride, Colleen M. TI Media Exposure and Genetic Literacy Skills to Evaluate Angelina Jolie's Decision for Prophylactic Mastectomy SO PUBLIC HEALTH GENOMICS LA English DT Article DE BRCA genetic mutations; Genetic literacy; Media; Prophylactic mastectomy; Public opinions ID RISK INFORMATION-SEEKING; BRCA2 MUTATION CARRIERS; BREAST-CANCER; BILATERAL MASTECTOMY; UNITED-STATES; IMPACT; KNOWLEDGE; ONLINE; PREVENTION; REDUCTION AB Purpose: To examine public preparedness to evaluate and respond to Angelina Jolie's well-publicized decision to have a prophylactic mastectomy. Methods: A consumer panel (n = 1,008) completed an online survey in November 2013, reporting exposure to Jolie's story, confidence applying genomic knowledge to evaluate her decision, and ability to interpret provided genetic risk information (genetic literacy skills). Linear and logistic regressions tested mediating/moderating models of these factors in association with opinions regarding mastectomies. Results: Confidence with genomics was associated with increased genetic literacy skills and increased media exposure, with a significant interaction between the two. Confidence was also associated with favoring mastectomies for women with BRCA mutations, mediating the relationship with media exposure. Respondents were more likely to form opinions about mastectomies if they had high genetic literacy skills. Conclusion: These findings suggest that having higher genetic literacy skills may increase the public's ability to form opinions about clinical applications of genomic discovery. However, repeated media exposure to high-profile stories may artificially inflate confidence among those with low genetic literacy. (C) 2016 S. Karger AG, Basel C1 [Abrams, Leah R.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Koehly, Laura M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Hooker, Gillian W.] NextGxDx, Franklin, TN USA. [Paquin, Ryan S.] RTI Int, Washington, DC USA. [Capella, Joseph N.] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA. [McBride, Colleen M.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. RP McBride, CM (reprint author), Emory Univ, Rollins Sch Publ Hlth, 1518-002-5AA SPH Behavrl Sci & Hlth, Atlanta, GA 30322 USA. EM ColleenMarieMcBride@emory.edu OI Paquin, Ryan/0000-0002-0947-7409 FU Intramural Research Program of the National Human Genome Research Institute (NHGRI) FX This work was supported by the Intramural Research Program of the National Human Genome Research Institute (NHGRI). Its content is solely the responsibility of the authors and does not necessarily represent the official views of the NHGRI or the National Institutes of Health. NR 37 TC 0 Z9 0 U1 4 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 EI 1662-8063 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2016 VL 19 IS 5 BP 282 EP 289 DI 10.1159/000447944 PG 8 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA DY1RN UT WOS:000384872200005 PM 27427958 ER PT S AU Smith, AP Munoz, CA Narkawicz, AJ Markevicius, M AF Smith, Andrew P. Munoz, Cesar A. Narkawicz, Anthony J. Markevicius, Mantas BE Kovacs, L Negru, V Ida, T Jebelean, T Petcu, D Watt, S Zaharie, D TI A Rigorous Generic Branch and Bound Solver for Nonlinear Problems SO 2015 17TH INTERNATIONAL SYMPOSIUM ON SYMBOLIC AND NUMERIC ALGORITHMS FOR SCIENTIFIC COMPUTING (SYNASC) SE International Symposium on Symbolic and Numeric Algorithms for Scientific Computing LA English DT Proceedings Paper CT 17th International Symposium on Symbolic and Numeric Algorithms for Scientific Computing (SYNASC) CY SEP 21-24, 2015 CL Timisoara, ROMANIA SP Univ Vest Timisoara, IEEE Comp Soc DE branch and bound; nonlinear problems; formal verification; interval arithmetic; software tool ID GLOBAL OPTIMIZATION; POLYNOMIALS; ALGORITHM AB Recursive branch and bound algorithms are often used, either rigorously or non-rigorously, to refine and isolate solutions to global optimization problems or systems of equations and inequalities involving nonlinear functions. The presented software library, Kodiak, integrates numeric and symbolic computation into a generic framework for the solution of such problems over hyper-rectangular variable and parameter domains. The correctness of both the generic branch and bound algorithm and the self-validating enclosure methods used, namely interval arithmetic and, for polynomials and rational functions, Bernstein expansion, has been formally verified. The algorithm has three main instantiations, for systems of equations and inequalities, for constrained global optimization, and for the computation of equilibria and bifurcation sets for systems of ordinary differential equations. For the latter category, and to enable the computation of bisection heuristics to reduce the branching factor, advantage is taken of the partial derivatives of the constraint functions, which are symbolically manipulated. Pavings (unions of box subsets) for a continuum of solutions to underdetermined systems may also be produced. The capabilities of the software tool are outlined, and computational examples are presented. C1 [Smith, Andrew P.] NIA, Hampton, VA 23666 USA. [Munoz, Cesar A.; Narkawicz, Anthony J.] NASA, Langley Res Ctr, Hampton, VA 23665 USA. [Markevicius, Mantas] Univ York, York, N Yorkshire, England. RP Smith, AP (reprint author), NIA, Hampton, VA 23666 USA. EM andrew.smith@nianet.org; cesar.a.munoz@nasa.gov; anthony.narkawicz@nasa.gov; mm1080@york.ac.uk NR 18 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2470-8801 BN 978-1-5090-0461-4 J9 INT SYMP SYMB NUMERI PY 2016 BP 71 EP 78 DI 10.1109/SYNASC.2015.20 PG 8 WC Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BF7ZG UT WOS:000384643800013 ER PT J AU Aas, S AF Aas, Sean TI Poverty, Agency, and Human Rights SO AUSTRALASIAN JOURNAL OF PHILOSOPHY LA English DT Book Review C1 [Aas, Sean] NIH, Bldg 10, Bethesda, MD 20892 USA. RP Aas, S (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0004-8402 EI 1471-6828 J9 AUSTRALAS J PHILOS JI Australas. J. Philos. PY 2016 VL 94 IS 3 BP 614 EP 617 DI 10.1080/00048402.2015.1092563 PG 6 WC Philosophy SC Philosophy GA DX5RC UT WOS:000384438100019 ER PT B AU Ambre, SG Barchi, JJ AF Ambre, Shailesh G. Barchi, Joseph J., Jr. BE Stine, KJ TI CARBOHYDRATE NANOTECHNOLOGY AND ITS APPLICATIONS FOR THE TREATMENT OF CANCER SO CARBOHYDRATE NANOTECHNOLOGY LA English DT Article; Book Chapter ID MAGNETIC GLYCO-NANOPARTICLES; ANTICANCER DRUG-DELIVERY; TUMOR-NECROSIS-FACTOR; GOLD NANOPARTICLES; QUANTUM DOTS; TARGETED DELIVERY; CHITOSAN NANOPARTICLES; DENDRITIC CELLS; COLLOIDAL GOLD; E-SELECTIN C1 [Ambre, Shailesh G.; Barchi, Joseph J., Jr.] NCI, Glycoconjugate & NMR Sect, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Ambre, SG (reprint author), NCI, Glycoconjugate & NMR Sect, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA. NR 207 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA BN 978-1-118-86024-3; 978-1-118-86053-3 PY 2016 BP 335 EP 368 PG 34 WC Biochemistry & Molecular Biology; Chemistry, Organic; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA BF8CO UT WOS:000384712300014 ER PT J AU Khanna, MM Badura-Brack, AS McDermott, TJ Shepherd, A Heinrichs-Graham, E Pine, DS Bar-Haim, Y Wilson, TW AF Khanna, Maya M. Badura-Brack, Amy S. McDermott, Timothy J. Shepherd, Alex Heinrichs-Graham, Elizabeth Pine, Daniel S. Bar-Haim, Yair Wilson, Tony W. TI Attention training normalises combat-related post-traumatic stress disorder effects on emotional Stroop performance using lexically matched word lists SO COGNITION & EMOTION LA English DT Article DE PTSD; attention training; emotional Stroop; lexically matched lists; attention bias modification ID RANDOMIZED CONTROLLED-TRIAL; BIAS MODIFICATION; ANXIETY DISORDERS; MODIFICATION PROGRAM; METAANALYSIS; THREAT; TASK AB We examined two groups of combat veterans, one with post-traumatic stress disorder (PTSD) (n=27) and another without PTSD (n=16), using an emotional Stroop task (EST) with word lists matched across a series of lexical variables (e.g. length, frequency, neighbourhood size, etc.). Participants with PTSD exhibited a strong EST effect (longer colour-naming latencies for combat-relevant words as compared to neutral words). Veterans without PTSD produced no such effect, t<.918, p>.37. Participants with PTSD then completed eight sessions of attention training (Attention Control Training or Attention Bias Modification Training) with a dot-probe task utilising threatening and neutral faces. After training, participantsespecially those undergoing Attention Control Trainingno longer produced longer colour-naming latencies for combat-related words as compared to other words, indicating normalised attention allocation processes after treatment. C1 [Khanna, Maya M.; Badura-Brack, Amy S.; McDermott, Timothy J.; Shepherd, Alex] Creighton Univ, Dept Psychol, Omaha, NE 68178 USA. [Heinrichs-Graham, Elizabeth] Univ Nebraska, Dept Psychol, Omaha, NE 68182 USA. [Pine, Daniel S.] NIMH, Rockville, MD 20857 USA. [Bar-Haim, Yair] Tel Aviv Univ, Sch Psychol Sci, Dept Psychol & Neurosci, Tel Aviv, Israel. [Wilson, Tony W.] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Dept Neurol Sci, Omaha, NE USA. [Wilson, Tony W.] Univ Nebraska Med Ctr, Ctr Magnetoencephalog, Omaha, NE USA. RP Khanna, MM (reprint author), Creighton Univ, Dept Psychol, Omaha, NE 68178 USA. EM mayakhanna@creighton.edu FU NIMH NIH HHS [R01 MH103220] NR 24 TC 3 Z9 3 U1 3 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0269-9931 EI 1464-0600 J9 COGNITION EMOTION JI Cogn. Emot. PY 2016 VL 30 IS 8 BP 1521 EP 1528 DI 10.1080/02699931.2015.1076769 PG 8 WC Psychology, Experimental SC Psychology GA DX8LW UT WOS:000384641200012 PM 26309165 ER PT J AU Kamal, MA Greig, NH AF Kamal, Mohammad A. Greig, Nigel H. TI Managing Strategies for Diverse Diseases: Challenges from Bench to Bedside Translation in Successful Drug Discovery and Development (Part C) SO CURRENT PHARMACEUTICAL DESIGN LA English DT Editorial Material ID SYSTEM; CANCER C1 [Kamal, Mohammad A.] King Abdulaziz Univ, Fundamental & Appl Biol Grp, King Fahd Med Res Ctr, Metabol & Enzymol Unit, POB 80216, Jeddah 21589, Saudi Arabia. [Kamal, Mohammad A.] Enzymoics, 7 Peterlee Pl, Hebersham, NSW 2770, Australia. [Kamal, Mohammad A.] Novel Global Community Educ Fdn, 7 Peterlee Pl, Hebersham, NSW 2770, Australia. [Kamal, Mohammad A.] Virtual Global Community Educ Org, 7 Peterlee Pl, Hebersham, NSW 2770, Australia. [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, NIH,Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. RP Kamal, MA (reprint author), King Abdulaziz Univ, Fundamental & Appl Biol Grp, King Fahd Med Res Ctr, Metabol & Enzymol Unit, POB 80216, Jeddah 21589, Saudi Arabia.; Kamal, MA (reprint author), Enzymoics, 7 Peterlee Pl, Hebersham, NSW 2770, Australia.; Kamal, MA (reprint author), Novel Global Community Educ Fdn, 7 Peterlee Pl, Hebersham, NSW 2770, Australia.; Kamal, MA (reprint author), Virtual Global Community Educ Org, 7 Peterlee Pl, Hebersham, NSW 2770, Australia. EM prof.makamal@lycos.com; greign@grc.nia.nihgov OI Kamal, Mohammad Amjad/0000-0003-0088-0565 NR 31 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2016 VL 22 IS 28 BP 4337 EP 4340 DI 10.2174/1381612822999160719150757 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DX9PO UT WOS:000384727800001 PM 27655557 ER PT J AU Ahmad, J Akhter, S Khan, MA Wahajuddin, M Greig, NH Kamal, MA Midoux, P Pichon, C AF Ahmad, Javed Akhter, Sohail Khan, Mohammad Ahmed Wahajuddin, Muhammad Greig, Nigel H. Kamal, Mohammad Amjad Midoux, Patrick Pichon, Chantal TI Engineered Nanoparticles Against MDR in Cancer: The State of the Art and its Prospective SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Multidrug resistance; MDR; efflux transporter; nanoparticles; passive targeting; active targeting; pH-sensitive; HIFU; combinational drug targeting ID OVERCOMING MULTIDRUG-RESISTANCE; MESOPOROUS SILICA NANOPARTICLES; TUMOR DRUG-RESISTANCE; LONG-CIRCULATING LIPOSOMES; SMALL INTERFERING RNA; CELLS IN-VITRO; BREAST-CANCER; CO-DELIVERY; P-GLYCOPROTEIN; GOLD NANOPARTICLES AB Cancer is a highly heterogeneous disease at intra/inter patient levels and known as the leading cause of death worldwide. A variety of mono and combinational therapies including chemotherapy have been evolved over the years for its effective treatment. However, advent of chemotherapeutic resistance or multidrug resistance (MDR) in cancer is a major challenge researchers are facing in cancer chemotherapy. MDR is a complex process having multifaceted non-cellular or cellular-based mechanisms. Research in the area of cancer nanotechnology over the past two decade has now proven that the smartly designed nanoparticles help in successful chemotherapy by overcoming the MDR and preferentially accumulate in the tumor region by means of active and passive targeting therefore reducing the offtarget accumulation of payload. Many of such nanoparticles are in different stages of clinical trials as nanomedicines showing promising result in cancer therapy including the resistant cases. Nanoparticles as chemotherapeutics carriers offer the opportunity to have multiple payload of drug and or imaging agents for combinational and theranostics therapy. Moreover, nanotechnology further bring in notice the new treatment strategies such as combining the NIR, MRI and HIFU in cancer chemotherapy and imaging. Here, we discussed the cellular/non-cellular factors constituting the MDR in cancer and the role of nanomedicines in effective chemotherapy of MDR cases of cancers. Moreover, recent advancements like combinational payload delivery and combined physical approach with nanotechnology in cancer therapy have also been discussed. C1 [Ahmad, Javed] Natl Inst Pharmaceut Educ & Res, Dept Pharmaceut, Raebareli 229010, UP, India. [Akhter, Sohail] LE STUDIUM Loire Valley Inst Adv Studies, Ctr Val De Loire Region, France. [Akhter, Sohail; Midoux, Patrick; Pichon, Chantal] CNRS UPR4301, Ctr Biophys Mol, Nucle Acids Transfer Nonviral Methods, Orleans, France. [Khan, Mohammad Ahmed] Jamia Hamdard, Dept Pharmacol, Fac Pharm, New Delhi 110062, India. [Wahajuddin, Muhammad] Cent Drug Res Inst, CSIR, Pharmacokinet & Metab Div, Lucknow 226031, Uttar Pradesh, India. [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH,Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. [Kamal, Mohammad Amjad] King Abdulaziz Univ, King Fahd Med Res Ctr, Fundamental & Appl Biol Grp, Metabol & Enzymol Unit, POB 80216, Jeddah 21589, Saudi Arabia. [Kamal, Mohammad Amjad] Enzymoics, 7 Peterlee Pl, Hebersham, NSW 2770, Australia. RP Akhter, S (reprint author), LE STUDIUM Loire Valley Inst Adv Studies, Nucle Acids Transfer Nonviral Methods, Ctr Biophys Mol, CNRS UPR4301, Orleans, France. EM sohailakhtermph@gmail.com OI Kamal, Mohammad Amjad/0000-0003-0088-0565 FU Intramural NIH HHS [ZIA AG000311-16] NR 187 TC 2 Z9 2 U1 7 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2016 VL 22 IS 28 BP 4360 EP 4373 DI 10.2174/1381612822666160617112111 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DX9PO UT WOS:000384727800003 PM 27319945 ER PT J AU Carleton, PF Schachter, S Parrish, JA Collins, JM Crocker, JB Dixon, RF Edgman-Levitan, S Lewandrowski, KB Stahl, JE Klapperich, C Cabodi, M Gaydos, CA Rompalo, AM Manabe, Y Wang, TH Rothman, R Geddes, CD Widdice, L Jackman, J Mathura, RA Lash, TB AF Carleton, Penny Ford Schachter, Steven Parrish, John A. Collins, John M. Crocker, J. Benjamin Dixon, Ronald F. Edgman-Levitan, Susan Lewandrowski, Kent B. Stahl, James E. Klapperich, Catherine Cabodi, Mario Gaydos, Charlotte A. Rompalo, Anne M. Manabe, Yukari Wang, Tza-Huei Rothman, Richard Geddes, Chris D. Widdice, Lea Jackman, Joany Mathura, Rishi A. Lash, Tiffani Bailey TI National Institute of Biomedical Imaging and Bioengineering Point-of-Care Technology Research Network: Advancing Precision Medicine SO IEEE JOURNAL OF TRANSLATIONAL ENGINEERING IN HEALTH AND MEDICINE-JTEHM LA English DT Article DE Point of care technologies; policy ID ISOTHERMAL AMPLIFICATION; CHLAMYDIA-TRACHOMATIS; AMBULATORY PRACTICE; CLINICAL-SAMPLES; DIAGNOSTICS; INFECTIONS; EXTRACTION; WORK; CHIP AB To advance the development of point-of-care technology (POCT), the National Institute of Biomedical Imaging and Bioengineering established the POCT Research Network (POCTRN), comprised of Centers that emphasize multidisciplinary partnerships and close facilitation to move technologies from an early stage of development into clinical testing and patient use. This paper describes the POCTRN and the three currently funded Centers as examples of academic-based organizations that support collaborations across disciplines, institutions, and geographic regions to successfully drive innovative solutions from concept to patient care. C1 [Carleton, Penny Ford; Schachter, Steven; Parrish, John A.; Collins, John M.] Consortium Improving Med Innovat & Technol, Boston, MA 02114 USA. [Carleton, Penny Ford; Schachter, Steven; Parrish, John A.; Collins, John M.; Crocker, J. Benjamin; Dixon, Ronald F.; Edgman-Levitan, Susan; Lewandrowski, Kent B.; Stahl, James E.] CIMIT Point Care Technol Res Ctr Primary Care, Boston, MA USA. [Schachter, Steven; Parrish, John A.; Crocker, J. Benjamin; Dixon, Ronald F.; Edgman-Levitan, Susan; Lewandrowski, Kent B.] Harvard Med Sch, Boston, MA 02115 USA. [Dixon, Ronald F.; Edgman-Levitan, Susan; Lewandrowski, Kent B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stahl, James E.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Klapperich, Catherine; Cabodi, Mario] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Klapperich, Catherine; Cabodi, Mario] BU Ctr Future Technol Canc Care, Boston, MA USA. [Gaydos, Charlotte A.; Rompalo, Anne M.; Manabe, Yukari; Wang, Tza-Huei; Rothman, Richard; Jackman, Joany] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Geddes, Chris D.] Univ Maryland, College Pk, MD 20742 USA. [Widdice, Lea] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Gaydos, Charlotte A.; Rompalo, Anne M.; Manabe, Yukari; Wang, Tza-Huei; Rothman, Richard; Geddes, Chris D.; Widdice, Lea; Jackman, Joany] JHU Ctr Excellence Dev & Testing Point Care Tests, Baltimore, MD USA. [Mathura, Rishi A.; Lash, Tiffani Bailey] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Schachter, S (reprint author), Consortium Improving Med Innovat & Technol, Boston, MA 02114 USA. EM sschacht@bidmc.harvard.edu NR 30 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2168-2372 J9 IEEE J TRANSL ENG HE JI IEEE J. Transl. Eng. Health Med.-JTEHM PY 2016 VL 4 AR 2800614 DI 10.1109/JTEHM.2016.2598837 PG 14 WC Engineering, Biomedical SC Engineering GA DX8OK UT WOS:000384648200001 PM 27730014 ER PT J AU Pearlman, PC Divi, R Gwede, M Tandon, P Sorg, BS Ossandon, MR Agrawal, L Pai, V Baker, H Lash, TB AF Pearlman, Paul C. Divi, Rao Gwede, Michael Tandon, Pushpa Sorg, Brian S. Ossandon, Miguel R. Agrawal, Lokesh Pai, Vinay Baker, Houston Lash, Tiffani Bailey TI The National Institutes of Health Affordable Cancer Technologies Program: Improving Access to Resource-Appropriate Technologies for Cancer Detection, Diagnosis, Monitoring, and Treatment in Low- and Middle-Income Countries SO IEEE JOURNAL OF TRANSLATIONAL ENGINEERING IN HEALTH AND MEDICINE-JTEHM LA English DT Article DE Cancer; cancer detection; medical diagnosis; cryotherapy; computer aided diagnosis AB Point-of-care (POC) technologies have proved valuable in cancer detection, diagnosis, monitoring, and treatment in the developed world, and have shown promise in low-and-middle-income countries (LMIC) as well. Despite this promise, the unique design constraints presented in low-resource settings, coupled with the variety of country-specific regulatory and institutional dynamics, have made it difficult for investigators to translate successful POC cancer interventions to the LMIC markets. In response to this need, the National Cancer Institute has partnered with the National Institute of Biomedical Imaging and Bioengineering to create the National Institutes of Health Affordable Cancer Technologies (ACTs) program. This program seeks to simplify the pathway to market by funding multidisciplinary investigative teams to adapt and validate the existing technologies for cancer detection, diagnosis, and treatment in LMIC settings. The various projects under ACTs range from microfluidic cancer diagnostic tools to novel treatment devices, each geared for successful clinical adaptation to LMIC settings. Via progression through this program, each POC innovation will be uniquely leveraged for successful clinical translation to LMICs in a way not before seen in this arena. C1 [Pearlman, Paul C.; Divi, Rao; Gwede, Michael; Tandon, Pushpa; Sorg, Brian S.; Ossandon, Miguel R.; Agrawal, Lokesh; Baker, Houston] NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Pai, Vinay; Lash, Tiffani Bailey] Natl Inst Biomed Imaging & Bioengn, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Pearlman, PC (reprint author), NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM paul.pearlman@nih.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2168-2372 J9 IEEE J TRANSL ENG HE JI IEEE J. Transl. Eng. Health Med.-JTEHM PY 2016 VL 4 AR 2800708 DI 10.1109/JTEHM.2016.2604485 PG 8 WC Engineering, Biomedical SC Engineering GA DX8OM UT WOS:000384648400001 PM 27730015 ER PT J AU Khund-Sayeed, S He, XM Holzberg, T Wang, J Rajagopal, D Upadhyay, S Durell, SR Mukherjee, S Weirauch, MT Rose, R Vinson, C AF Khund-Sayeed, Syed He, Ximiao Holzberg, Timothy Wang, Jun Rajagopal, Divya Upadhyay, Shriyash Durell, Stewart R. Mukherjee, Sanjit Weirauch, Matthew T. Rose, Robert Vinson, Charles TI 5-Hydroxymethylcytosine in E-box motifs ACAT|GTG and ACAC|GTG increases DNA-binding of the B-HLH transcription factor TCF4 SO INTEGRATIVE BIOLOGY LA English DT Article ID RESOLUTION ANALYSIS; CG DINUCLEOTIDE; BASE-RESOLUTION; PROTEIN-BINDING; TET PROTEINS; METHYLATION; GENOME; 5-METHYLCYTOSINE; RECOGNITION; HETERODIMER AB We evaluated DNA binding of the B-HLH family members TCF4 and USF1 using protein binding microarrays (PBMs) containing double-stranded DNA probes with cytosine on both strands or 5-methylcytosine (5mC) or 5-hydroxymethylcytosine (5hmC) on one DNA strand and cytosine on the second strand. TCF4 preferentially bound the E-box motif (CAN|NTG) with strongest binding to the 8-mer CAG|GTGGT. 5mC uniformly decreases DNA binding of both TCF4 and USF1. The bulkier 5hmC also inhibited USF1 binding to DNA. In contrast, 5hmC dramatically enhanced TCF4 binding to E-box motifs ACAT|GTG and ACAC|GTG, being better bound than any 8-mer containing cytosine. Examination of X-ray structures of the closely related TCF3 and USF1 bound to DNA suggests TCF3 can undergo a conformational shift to preferentially bind to 5hmC while the USF1 basic region is bulkier and rigid precluding a conformation shift to bind 5hmC. These results greatly expand the regulatory DNA sequence landscape bound by TCF4. C1 [Khund-Sayeed, Syed; He, Ximiao; Holzberg, Timothy; Wang, Jun; Rajagopal, Divya; Upadhyay, Shriyash; Mukherjee, Sanjit; Vinson, Charles] NCI, Lab Metab, NIH, Room 3128,Bldg 37, Bethesda, MD 20892 USA. [Durell, Stewart R.] NCI, Cell Biol Lab, NIH, Room 3035B,Bldg 37, Bethesda, MD 20892 USA. [Weirauch, Matthew T.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol,Div Biomed Informat, Cincinnati, OH 45229 USA. [Weirauch, Matthew T.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Dev Biol,Dept Pediat, Cincinnati, OH 45229 USA. [Rose, Robert] North Carolina State Univ, Dept Biochem, Raleigh, NC 27695 USA. RP Vinson, C (reprint author), NCI, Lab Metab, NIH, Room 3128,Bldg 37, Bethesda, MD 20892 USA. EM vinsonc@mail.nih.gov FU intramural research project of National Cancer Institute, NIH, Bethesda, USA FX This work is supported by the intramural research project of National Cancer Institute, NIH, Bethesda, USA. NR 36 TC 1 Z9 1 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 EI 1757-9708 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2016 VL 8 IS 9 BP 936 EP 945 DI 10.1039/c6ib00079g PG 10 WC Cell Biology SC Cell Biology GA DX2LM UT WOS:000384201300004 PM 27485769 ER PT B AU Hardway, C McCartney, K AF Hardway, Christina McCartney, Kathleen BE Durkin, K Schaffer, HR TI Child Care at the Nexus of Practice, Policy, and Research SO WILEY HANDBOOK OF DEVELOPMENTAL PSYCHOLOGY IN PRACTICE: IMPLEMENTATION AND IMPACT SE Blackwell Handbooks of Developmental Psychology LA English DT Article; Book Chapter ID LANGUAGE-DEVELOPMENT; CAREGIVER STABILITY; YOUTH DEVELOPMENT; HOME-ENVIRONMENT; QUALITY; ATTACHMENT; NICHD; TIME; INTERVENTION; ACHIEVEMENT C1 [Hardway, Christina] Merrimack Coll, Dept Psychol, N Andover, MA 01845 USA. [McCartney, Kathleen] Smith Coll, Northampton, MA 01063 USA. [McCartney, Kathleen] Harvard Univ, Educ, Cambridge, MA 02138 USA. [McCartney, Kathleen] NICHD Early Child Care Res Network, Rockville, MD USA. [McCartney, Kathleen] Amer Acad Arts & Sci, Cambridge, MA USA. RP Hardway, C (reprint author), Merrimack Coll, Dept Psychol, N Andover, MA 01845 USA. NR 89 TC 0 Z9 0 U1 4 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-119-09567-5; 978-1-4051-6336-1 J9 BL HBK DEV PSYCHOL PY 2016 BP 143 EP 170 D2 10.1002/9781119095699 PG 28 WC Psychology, Developmental SC Psychology GA BF7FC UT WOS:000384000100008 ER PT B AU Cicchetti, D Toth, SL Nilsen, WJ Manly, JT AF Cicchetti, Dante Toth, Sheree L. Nilsen, Wendy J. Manly, Jody Todd BE Durkin, K Schaffer, HR TI What Do We Know and Why Does It Matter? The Dissemination of Evidence-Based Interventions for Child Maltreatment SO WILEY HANDBOOK OF DEVELOPMENTAL PSYCHOLOGY IN PRACTICE: IMPLEMENTATION AND IMPACT SE Blackwell Handbooks of Developmental Psychology LA English DT Article; Book Chapter ID DEVELOPMENTAL PSYCHOPATHOLOGY PERSPECTIVE; BORDERLINE PERSONALITY-DISORDER; LINKED POLYMORPHIC REGION; ATTACHMENT THEORY; HOME VISITATION; REPRESENTATIONAL MODELS; DISORGANIZED ATTACHMENT; MATERNAL-BEHAVIOR; SOCIAL COMPETENCE; YOUNG-CHILDREN C1 [Cicchetti, Dante] Univ Minnesota, Child Dev & Psychiat, Minneapolis, MN 55455 USA. [Toth, Sheree L.; Manly, Jody Todd] Univ Rochester, Mt Hope Family Ctr, Rochester, NY 14627 USA. [Toth, Sheree L.] Univ Rochester, Clin Training, Rochester, NY 14627 USA. [Toth, Sheree L.] Univ Rochester, Psychol, Rochester, NY 14627 USA. [Nilsen, Wendy J.] NIH, OBSSR, New York, NY USA. [Manly, Jody Todd] Univ Rochester, Dept Clin & Social Sci Psychol, Rochester, NY 14627 USA. RP Cicchetti, D (reprint author), Univ Minnesota, Child Dev & Psychiat, Minneapolis, MN 55455 USA. NR 126 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-119-09567-5; 978-1-4051-6336-1 J9 BL HBK DEV PSYCHOL PY 2016 BP 369 EP 406 D2 10.1002/9781119095699 PG 38 WC Psychology, Developmental SC Psychology GA BF7FC UT WOS:000384000100016 ER PT B AU Puri, M Solanki, A Padawer, T Tipparaju, SM Moreno, WA Pathak, Y AF Puri, Munish Solanki, Aum Padawer, Timothy Tipparaju, Srinivas M. Moreno, Wilfrido Alejandro Pathak, Yashwant BE Puri, M Pathak, Y Sutariya, VK Tipparaju, S Moreno, W TI Introduction to Artificial Neural Network (ANN) as a Predictive Tool for Drug Design, Discovery, Delivery, and Disposition: Basic Concepts and Modeling SO ARTIFICIAL NEURAL NETWORK FOR DRUG DESIGN, DELIVERY AND DISPOSITION LA English DT Editorial Material; Book Chapter ID BLOOD-BRAIN-BARRIER; IN-VIVO CORRELATIONS; PHYSICOCHEMICAL PROPERTIES; RETENTION TIME; VITRO; SILICO; CHROMATOGRAPHY; PERMEABILITY; FORMULATION; ABSORPTION C1 [Puri, Munish] NCI, NIH, Bethesda, MD 20892 USA. [Solanki, Aum; Padawer, Timothy; Tipparaju, Srinivas M.] Univ S Florida, Dept Pharmaceut Sci, Coll Pharm, Tampa, FL USA. [Moreno, Wilfrido Alejandro] Univ S Florida, Dept Elect Engn, Tampa, FL USA. [Moreno, Wilfrido Alejandro] Ibero Amer Sci & Technol Educ Consortium ISTEC, R&D, Tampa, FL USA. [Pathak, Yashwant] Univ S Florida, USF Coll Pharm, Tampa, FL USA. RP Puri, M (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 29 TC 2 Z9 2 U1 1 U2 1 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-801744-9; 978-0-12-801559-9 PY 2016 BP 3 EP 13 DI 10.1016/B978-0-12-801559-9.00001-6 PG 11 WC Computer Science, Interdisciplinary Applications; Pharmacology & Pharmacy SC Computer Science; Pharmacology & Pharmacy GA BF8AB UT WOS:000384668300003 ER PT B AU Puri, M Pathak, Y Sutariya, VK Tipparaju, S Moreno, W AF Puri, Munish Pathak, Yashwant Sutariya, Vijay Kumar Tipparaju, Srinivas Moreno, Wilfrido BE Puri, M Pathak, Y Sutariya, VK Tipparaju, S Moreno, W TI Artificial Neural Network for Drug Design, Delivery and Disposition Preface SO ARTIFICIAL NEURAL NETWORK FOR DRUG DESIGN, DELIVERY AND DISPOSITION LA English DT Editorial Material; Book Chapter C1 [Puri, Munish] Univ S Florida, Elect Engn, Tampa, FL 33620 USA. [Puri, Munish] H Lee Moffitt Canc Ctr & Res Inst, Analyt Microscopy, Tampa, FL 33612 USA. [Puri, Munish] NCI, NIH, Bethesda, MD 20892 USA. [Pathak, Yashwant] Univ S Florida, USF Coll Pharm, Tampa, FL USA. [Tipparaju, Srinivas] Univ S Florida, Dept Pharmaceut Sci, Coll Pharm, Tampa, FL USA. [Moreno, Wilfrido] Univ S Florida, Dept Elect Engn, Tampa, FL USA. [Moreno, Wilfrido] Ibero Amer Sci & Technol Educ Consortium ISTEC, R&D, Tampa, FL USA. RP Puri, M (reprint author), Univ S Florida, Elect Engn, Tampa, FL 33620 USA.; Puri, M (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Analyt Microscopy, Tampa, FL 33612 USA.; Puri, M (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-801744-9; 978-0-12-801559-9 PY 2016 BP XXI EP XXIII PG 3 WC Computer Science, Interdisciplinary Applications; Pharmacology & Pharmacy SC Computer Science; Pharmacology & Pharmacy GA BF8AB UT WOS:000384668300002 ER PT B AU Puri, M Lloyd, M Bui, M AF Puri, Munish Lloyd, Mark Bui, Marilyn BE Puri, M Pathak, Y Sutariya, VK Tipparaju, S Moreno, W TI Role of an Artificial Neural Network Classifier in Nuclear Pleomorphic Feature Analysis of Histopathological Images of Breast Cancer SO ARTIFICIAL NEURAL NETWORK FOR DRUG DESIGN, DELIVERY AND DISPOSITION LA English DT Article; Book Chapter ID SEGMENTATION; CARCINOMA; PATHOLOGY; SECTIONS; BIOPSY C1 [Puri, Munish] Univ S Florida, Elect Engn, Tampa, FL 33620 USA. [Bui, Marilyn] Univ S Florida, Pathol & Cell Biol, Tampa, FL USA. [Puri, Munish; Lloyd, Mark; Bui, Marilyn] H Lee Moffitt Canc Ctr & Res Inst, Analyt Microscopy, Tampa, FL 33612 USA. [Puri, Munish] NCI, NIH, Bethesda, MD 20892 USA. RP Puri, M (reprint author), Univ S Florida, Elect Engn, Tampa, FL 33620 USA.; Puri, M (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Analyt Microscopy, Tampa, FL 33612 USA.; Puri, M (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 31 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-801744-9; 978-0-12-801559-9 PY 2016 BP 377 EP 391 DI 10.1016/B978-0-12-801559-9.00019-3 PG 15 WC Computer Science, Interdisciplinary Applications; Pharmacology & Pharmacy SC Computer Science; Pharmacology & Pharmacy GA BF8AB UT WOS:000384668300021 ER PT J AU Kuramoto, K Wang, N Fan, YY Zhang, WR Schoenen, FJ Frankowski, KJ Marugan, J Zhou, YF Huang, S He, CC AF Kuramoto, Kenta Wang, Nan Fan, Yuying Zhang, Weiran Schoenen, Frank J. Frankowski, Kevin J. Marugan, Juan Zhou, Yifa Huang, Sui He, Congcong TI Autophagy activation by novel inducers prevents BECN2-mediated drug tolerance to cannabinoids SO AUTOPHAGY LA English DT Article DE analgesia; autophagy inducer; BECN2; behavior; cannabinoid; cannabinoid receptor 1; drug tolerance; intracellular trafficking ID PROTEIN-COUPLED RECEPTORS; MEDICAL MARIJUANA; ANIMAL-MODELS; CHRONIC PAIN; METAANALYSIS; MECHANISMS; ADDICTION; BECLIN-1; TISSUES; CELLS AB Cannabinoids and related drugs generate profound behavioral effects (such as analgesic effects) through activating CNR1 (cannabinoid receptor 1 [brain]). However, repeated cannabinoid administration triggers lysosomal degradation of the receptor and rapid development of drug tolerance, limiting the medical use of marijuana in chronic diseases. The pathogenic mechanisms of cannabinoid tolerance are not fully understood, and little is known about its prevention. Here we show that a protein involved in macroautophagy/autophagy (a conserved lysosomal degradation pathway), BECN2 (beclin 2), mediates cannabinoid tolerance by preventing CNR1 recycling and resensitization after prolonged agonist exposure, and deletion of Becn2 rescues CNR1 activity in mouse brain and conveys resistance to analgesic tolerance to chronic cannabinoids. To target BECN2 therapeutically, we established a competitive recruitment model of BECN2 and identified novel synthetic, natural or physiological stimuli of autophagy that sequester BECN2 from its binding with GPRASP1, a receptor protein for CNR1 degradation. Co-administration of these autophagy inducers effectively restores the level and signaling of brain CNR1 and protects mice from developing tolerance to repeated cannabinoid usage. Overall, our findings demonstrate the functional link among autophagy, receptor signaling and animal behavior regulated by psychoactive drugs, and develop a new strategy to prevent tolerance and improve medical efficacy of cannabinoids by modulating the BECN2 interactome and autophagy activity. C1 [Kuramoto, Kenta; Wang, Nan; Fan, Yuying; Zhang, Weiran; Huang, Sui; He, Congcong] Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA. [Wang, Nan] Tianjin Univ Sci & Technol, Coll Biotechnol, Key Lab Ind Microbiol, Minist Educ & Tianjin City, Tianjin, Peoples R China. [Fan, Yuying; Zhou, Yifa] Northeast Normal Univ, Sch Life Sci, Changchun, Jilin, Peoples R China. [Schoenen, Frank J.] Univ Kansas, Higuchi Biosci Ctr, Lawrence, KS 66045 USA. [Frankowski, Kevin J.] Univ North Carolina Chapel Hill, UNC Eshelman Sch Pharm, Chapel Hill, NC USA. [Marugan, Juan] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA. [Kuramoto, Kenta] Yamagata Univ, Sch Med, Dept Mol Canc Sci, Yamagata 9909585, Japan. RP He, CC (reprint author), 300 E Super St,Tarry 8-767, Chicago, IL 60611 USA. EM congcong.he@northwestern.edu FU University of Kansas Specialized Chemistry Center [U54HG005031]; National Natural Science Foundation of China [31470798, 31300287, 31171303]; Doctoral Fund of Ministry of Education of China [20120043130001]; National Institutes of Health [GM078555, DK094980]; Northwestern University FX Synthesis of ML246 was supported by the University of Kansas Specialized Chemistry Center (Molecular Libraries Initiative grant U54HG005031 from National Institutes of Health, Jeffrey Aube PI). Y. Z. was supported by the grant from National Natural Science Foundation of China (No. 31470798) and the Doctoral Fund of Ministry of Education of China (No. 20120043130001). S. H. was supported by the grant from National Institutes of Health (GM078555). K. K., N. W., Y. F., W. Z. and C. H. were supported by the startup funds from Northwestern University and the grant from National Institutes of Health (DK094980). Y. F. was also supported by the National Natural Science Foundation of China (Grant No. 31300287). N. W. was also supported by the National Natural Science Foundation of China (Grant No. 31171303). NR 35 TC 1 Z9 1 U1 2 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PY 2016 VL 12 IS 9 BP 1460 EP 1471 DI 10.1080/15548627.2016.1187367 PG 12 WC Cell Biology SC Cell Biology GA DW9ZT UT WOS:000384022000005 PM 27305347 ER PT J AU Weyemi, U Redon, CE Sethi, TK Burrell, AS Jailwala, P Kasoji, M Abrams, N Merchant, A Bonner, WM AF Weyemi, Urbain Redon, Christophe E. Sethi, Taresh K. Burrell, Allison S. Jailwala, Parthav Kasoji, Manjula Abrams, Natalie Merchant, Anand Bonner, William M. TI Twist1 and Slug mediate H2AX-regulated epithelial-mesenchymal transition in breast cells SO CELL CYCLE LA English DT Editorial Material DE breast cancer; EMT; histone H2AX; Slug; Twist1 ID TUMOR-METASTASIS; CANCER CELLS; E-CADHERIN; MOLECULAR-MECHANISMS; GENE-EXPRESSION; DNA METHYLATION; PROGRESSION; PLASTICITY; REPRESSOR; INVASION AB The epithelial-mesenchymal transition (EMT) is thought to be essential for cancer metastasis. While chromatin remodeling is involved in EMT, which processes contribute to this remodeling remain poorly investigated. Recently, we showed that silencing or removal of the histone variant H2A.X induced mesenchymal-like characteristics, including activation of the EMT transcription factors, Slug and Zeb1 in human colon cancer cells.Here, we provide the evidence that H2A.X loss in human non-tumorigenic breast cell line MCF10A results in a robust EMT activation, as substantiated by a genome-wide expression analysis. Cells deficient for H2A.X exhibit enhanced migration and invasion, along with an activation of a set of mesenchymal genes and a concomitant repression of epithelial genes. In the breast model, the EMT-related transcription factor Twist1 cooperates with Slug to regulate EMT upon H2A.X Loss. Of interest, H2A.X expression level tightly correlates with Twist1, and to a lesser extent with Slug in the panel of human breast cancer cell lines of the NCI-60 datasets. These new findings indicate that H2A.X is involved in the EMT processes in cells of different origins but pairing with transcription factors for EMT may be tissue specific. C1 [Weyemi, Urbain; Redon, Christophe E.; Sethi, Taresh K.; Burrell, Allison S.; Bonner, William M.] NCI, Dev Therapeut Branch, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. [Weyemi, Urbain] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD USA. [Jailwala, Parthav; Kasoji, Manjula; Abrams, Natalie; Merchant, Anand] NCI, Ctr Canc Res Collaborat Bioinformat Resource, Bethesda, MD 20892 USA. RP Bonner, WM (reprint author), NCI, Bldg 37,Room 5050A,9000 Rockville Pike, Bethesda, MD 20892 USA.; Weyemi, U (reprint author), Johns Hopkins Univ, Dept Neurosci, Solomon Snyders Lab, 725 N Wolfe St,WBSB 816, Baltimore, MD 21205 USA. EM sweyemi1@jhmi.edu; bonnerw@mail.nih.gov NR 34 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2016 VL 15 IS 18 BP 2398 EP 2404 DI 10.1080/15384101.2016.1198864 PG 7 WC Cell Biology SC Cell Biology GA DW9ZV UT WOS:000384022200009 PM 27315462 ER PT J AU Ojo-Carons, M Mumford, SL Armstrong, AY DeCherney, AH Devine, K AF Ojo-Carons, Mary Mumford, Sunni L. Armstrong, Alicia Y. DeCherney, Alan H. Devine, Kate TI Is Myomectomy Prior to Assisted Reproductive Technology Cost Effective in Women with Intramural Fibroids? SO GYNECOLOGIC AND OBSTETRIC INVESTIGATION LA English DT Article DE Assisted reproductive technology; Myomectomy; Intramural; Cost effectiveness; Ongoing pregnancy; Live birth ID IN-VITRO FERTILIZATION; UTERINE FIBROIDS; ENDOMETRIAL CAVITY; IMPACT; INFERTILITY; CONCEPTION; MANAGEMENT; FERTILITY; IVF AB Aim: To evaluate the cost effectiveness of surgery to remove intramural (IM) fibroids prior to assisted reproductive technology (ART). Methods: The decision tree mathematical model along with sensitivity analysis was performed to analyze cost effectiveness of: (1) myomectomy followed by ART or (2) ART with IM myoma(s) in situ. Results: At the median ongoing pregnancy (OP) rate (OPR) reported in the literature for a fresh, autologous ART cycle with IM fibroids in situ vs. post-IM myomectomy, average cost per OP was $72,355 vs. 66,075, indicating a cost savings with myomectomy. Sensitivity analysis over the range of reported OPRs demonstrated that pre-ART IM myomectomy was always cost effective when OPR among women with in situ myomas was <15.4%. However, for OPRs ?_15.4%, pre-ART IM myomectomy was only cost effective if it increased OPR by at least 9.6%. At the high end of OPRs reported for patients with IM myomas in situ (31.4%), a 19.5% improvement in OPR was needed to justify IM myomectomy from a cost perspective. Conclusion: Myomectomy should be used sparingly in cases where the goal of surgery is to achieve improvement in the outcomes of ART. (C) 2016 S. Karger AG, Basel C1 [Ojo-Carons, Mary] Mt Sinai Sch Med, Dept Obstet Gynecol & Reprod Serv, New York, NY USA. [Mumford, Sunni L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Epidemiol Branch, Div Intramural Populat Hlth Res, Rockville, MD USA. [Armstrong, Alicia Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Contracept Discovery & Dev Branch, Bethesda, MD USA. [DeCherney, Alan H.; Devine, Kate] NIH, Program Reprod & Adult Endocrinol, Bldg 10, Bethesda, MD 20892 USA. RP Devine, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 10 Ctr Dr,MSC 1109,Rm 1-3140, Bethesda, MD 20892 USA. EM kate.devine@nih.gov FU Program in Reproductive and Adult Endocrinology, the Intramural Research Program, NICHD, NIH FX This was presented at the 2013 Society for Gynecologic Investigation's 60th Annual Scientific Meeting. This study was supported by the Program in Reproductive and Adult Endocrinology, the Intramural Research Program, NICHD, NIH. NR 25 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-7346 EI 1423-002X J9 GYNECOL OBSTET INVES JI Gynecol.Obstet.Invest. PY 2016 VL 81 IS 5 BP 442 EP 446 DI 10.1159/000443391 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DX0EN UT WOS:000384034700009 PM 26990761 ER PT J AU Binukumar, BK Pelech, SL Sutter, C Shukla, V Amin, ND Grant, P Bhaskar, M Skuntz, S Steiner, J Pant, HC AF Binukumar, B. K. Pelech, Steven L. Sutter, Catherine Shukla, Varsha Amin, Niranjana D. Grant, Philip Bhaskar, Manju Skuntz, Suzanne Steiner, Joseph Pant, Harish C. TI Profiling of p5, a 24 Amino Acid Inhibitory Peptide Derived from the CDK5 Activator, p35 CDKR1 Against 70 Protein Kinases SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; cyclin-dependent kinase 5 activator; p35 CDK5R1; tau phosphorylation ID CYCLIN-DEPENDENT KINASE-5; ALZHEIMERS-DISEASE; TAU HYPERPHOSPHORYLATION; SYNAPTIC PLASTICITY; NEURONAL ACTIVATOR; P25; DEATH; CALPAIN; NEURODEGENERATION; PHOSPHORYLATION AB Cyclin-dependent kinase 5 (CDK5) is a multifunctional serine/threonine kinase that regulates a large number of neuronal processes essential for nervous system development and function with its activator p35 CDK5R1. Upon neuronal insults, p35 is proteolyzed and cleaved to p25 producing deregulation and hyperactivation of CDK5 (CDK5/p25), implicated in tau hyperphosphorylation, a pathology in some neurodegenerative diseases. A truncated, 24 amino acid peptide, p5, derived from p35 inhibits the deregulated CDK5 phosphotransferase activity and ameliorates Alzheimer's disease (AD) phenotypes in AD model mice. In the present study, we have screened a diverse panel of 70 human protein kinases for their sensitivities to p5, and a subset of these to p35. At least 16 of the tested protein kinases exhibited IC50 values that were 250 mu M or less, with CAMK4, ZAP70, SGK1, and PIM1 showing greater sensitivity to inhibition by p5 than CDK5/p35 and CDK5/p25. In contrast, the p5 peptide modestly activated LKB1 and GSK3 beta. A sub set of kinases screened against p35 showed that activity of CAMK4 in the absence of calcium and calmodulin was also markedly inhibited by p35. The Cyclin Y-dependent kinases PFTK1 (CDK14) and PCTK1 (CDK16) were activated by p35 at least 10-fold in the absence of Cyclin Y and by approximately 50% in its presence. These findings provide additional insights into the mechanisms of action for p5 and p35 in the regulation of protein phosphorylation in the nervous system. C1 [Binukumar, B. K.; Shukla, Varsha; Amin, Niranjana D.; Grant, Philip; Bhaskar, Manju; Skuntz, Suzanne; Steiner, Joseph; Pant, Harish C.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Pelech, Steven L.; Sutter, Catherine] Kinexus Bioinformat Corp, Vancouver, BC, Canada. [Pelech, Steven L.; Sutter, Catherine] Univ British Columbia, Div Neurol, Dept Med, Vancouver, BC V5Z 1M9, Canada. RP Pant, HC (reprint author), NINDS, Lab Neuronal Cytoskeletal Prot Regulat Sect, NIH, Bethesda, MD 20892 USA. EM pantH@ninds.nih.gov FU intramural research program of the U.S. National Institute of Neurological Disease and Stroke, National Institutes of Health FX This work was supported by the intramural research program of the U.S. National Institute of Neurological Disease and Stroke, National Institutes of Health. NR 37 TC 0 Z9 0 U1 3 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2016 VL 54 IS 2 BP 525 EP 533 DI 10.3233/JAD-160458 PG 9 WC Neurosciences SC Neurosciences & Neurology GA DX0WO UT WOS:000384087200010 PM 27567857 ER PT J AU Murelli, RP D'Erasmo, MP Hirsch, DR Meck, C Masaoka, T Wilson, JA Zhang, BF Pal, RK Gallicchio, E Beutlere, JA Le Grice, SFJ AF Murelli, Ryan P. D'Erasmo, Michael P. Hirsch, Danielle R. Meck, Christine Masaoka, Takashi Wilson, Jennifer A. Zhang, Baofeng Pal, Rajat K. Gallicchio, Emilio Beutlere, John A. Le Grice, Stuart F. J. TI Synthetic alpha-hydroxytropolones as inhibitors of HIV reverse transcriptase ribonuclease H activity SO MEDCHEMCOMM LA English DT Article ID B-VIRUS REPLICATION; RNASE-H; HYDROXYLATED TROPOLONES; ASSAY; BLOCKING; ENERGY; SCALE; ACID; SITE AB HIV reverse transcriptase-associated ribonuclease H activity is a promising enzymatic target for drug development that has not been successfully targeted in the clinic. While the alpha-hydroxytropolone-containing natural products beta-thujaplicinol and manicol have emerged as some of the most potent leads described to date, structure-function studies have been limited to the natural products and semi-synthetic derivatives of manicol. Thus, a library of alpha-hydroxytropolones synthesized through a convenient oxidopyrylium cycloaddition/ring-opening sequence have been tested in in vitro and cell-based assays, and have been analyzed using computational support. These studies reveal new synthetic alpha-hydroxytropolones that, unlike the natural product leads they are derived from, demonstrate protective antiviral activity in cellular assays. C1 [Murelli, Ryan P.; D'Erasmo, Michael P.; Hirsch, Danielle R.; Meck, Christine; Zhang, Baofeng; Pal, Rajat K.; Gallicchio, Emilio] CUNY Brooklyn, Dept Chem, Brooklyn Coll, New York, NY 11210 USA. [Murelli, Ryan P.; D'Erasmo, Michael P.; Hirsch, Danielle R.; Meck, Christine; Gallicchio, Emilio] CUNY, Grad Ctr, PhD Program Chem, New York, NY USA. [Pal, Rajat K.; Gallicchio, Emilio] CUNY, Grad Ctr, PhD Program Biochem, New York, NY USA. [Masaoka, Takashi; Le Grice, Stuart F. J.] Natl Canc Inst Frederick, Basic Res Lab, Ctr Canc Res, Frederick, MD USA. [Wilson, Jennifer A.; Beutlere, John A.] Natl Canc Inst Frederick, Mol Targets Lab, Ctr Canc Res, Frederick, MD USA. RP Murelli, RP (reprint author), CUNY Brooklyn, Dept Chem, Brooklyn Coll, New York, NY 11210 USA.; Murelli, RP (reprint author), CUNY, Grad Ctr, PhD Program Chem, New York, NY USA. EM rpmurelli@brooklyn.cuny.edu FU National Instituted of Health [SC1GM111158]; Alfred P. Sloan Foundation; National Cancer Institute, National Institutes of Health, Department of Health and Human Services; National Science Foundation [SI2-SSE 1440665]; Brooklyn College Research Foundation; [MCB150001] FX MD, CM, DH, RP, and RM are grateful for support from The National Instituted of Health (SC1GM111158), and the Alfred P. Sloan Foundation. TM, JB, JW and SL are supported by the intramural research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. E. G. acknowledges support from the National Science Foundation (SI2-SSE 1440665). B. Z. acknowledges support from the Brooklyn College Research Foundation. Binding free energy calculations were carried out on the SuperMIC cluster of XSEDE (supported by MCB150001), and the WEB computing grid at Brooklyn College of the City University of New York. NR 33 TC 0 Z9 0 U1 1 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 EI 2040-2511 J9 MEDCHEMCOMM JI MedChemComm PY 2016 VL 7 IS 9 BP 1783 EP 1788 DI 10.1039/c6md00238b PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA DX3ES UT WOS:000384256800009 PM 28093576 ER PT J AU D'Erasmo, MP Masaoka, T Wilson, JA Hunte, EM Beutler, JA Le Grice, SFJ Murelli, RP AF D'Erasmo, Michael P. Masaoka, Takashi Wilson, Jennifer A. Hunte, Errol M., Jr. Beutler, John A. Le Grice, Stuart F. J. Murelli, Ryan P. TI Traceless solid-phase alpha-hydroxytropolone synthesis SO MEDCHEMCOMM LA English DT Article ID RIBONUCLEASE-H ACTIVITY; HIV-1 REVERSE-TRANSCRIPTASE; B-VIRUS REPLICATION; RNASE-H; HYDROXYLATED TROPOLONES; NATURAL-PRODUCTS; INHIBITORS; CYCLOADDITION; BLOCKING; ENZYMES AB alpha-Hydroxytropolones are established inhibitors of several therapeutically relevant binuclear meta-lloenzymes, and thus lead drug targets for various human diseases. We have leveraged a recently-disclosed three-component oxidopyrylium cycloaddition in the first solid-phase synthesis of alpha-hydroxytropolones. We also showed that, while minor impurities exist after cleavage and aqueous wash, the semi-crude products display activity in HIV RT-associated RNaseH enzymatic and cell-based assays consistent with pure molecules made in solution phase. These proof-of-principle studies demonstrate the feasibility of solid-phase alpha-hydroxytropolone synthesis and its potential to serve as a powerful platform for alpha-hydroxytropolone-based drug discovery and development. C1 [D'Erasmo, Michael P.; Hunte, Errol M., Jr.; Murelli, Ryan P.] CUNY, Dept Chem, Brooklyn Coll, Brooklyn, NY 11210 USA. [D'Erasmo, Michael P.; Murelli, Ryan P.] CUNY, Grad Ctr, PhD Program Chem, New York, NY USA. [Masaoka, Takashi; Le Grice, Stuart F. J.] Natl Canc Inst Frederick, Basic Res Lab, Ctr Canc Res, Frederick, MD USA. [Wilson, Jennifer A.; Beutler, John A.] Natl Canc Inst Frederick, Mol Targets Lab, Ctr Canc Res, Frederick, MD USA. RP Murelli, RP (reprint author), CUNY, Dept Chem, Brooklyn Coll, Brooklyn, NY 11210 USA.; Murelli, RP (reprint author), CUNY, Grad Ctr, PhD Program Chem, New York, NY USA. EM rpmurelli@brooklyn.cuny.edu FU National Instituted of Health [SC1GM111158]; Alfred P. Sloan Foundation; National Cancer Institute, National Institutes of Health, Department of Health and Human Services FX MD and RM are grateful for support from The National Instituted of Health (SC1GM111158), and the Alfred P. Sloan Foundation. TM, JB, JW and SL are supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 25 TC 0 Z9 0 U1 1 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 EI 2040-2511 J9 MEDCHEMCOMM JI MedChemComm PY 2016 VL 7 IS 9 BP 1789 EP 1792 DI 10.1039/c6md00237d PG 4 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA DX3ES UT WOS:000384256800010 PM 28090282 ER PT S AU Wrobel, TP Kwak, JT Kadjacsy-Balla, A Bhargava, R AF Wrobel, Tomasz P. Kwak, Jin Tae Kadjacsy-Balla, Andre Bhargava, Rohit BE Gurcan, MN Madabhushi, A TI High-Definition Fourier Transform Infrared Spectroscopic Imaging of Prostate Tissue SO MEDICAL IMAGING 2016: DIGITAL PATHOLOGY SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Digital Pathology CY MAR 02-03, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD DE imaging; Fourier transform infrared spectroscopy; high definition; cancer; random forest; hierarchical cluster analysis ID FT-IR SPECTROSCOPY; APOE/LDLR-/-MICE; CANCER; RESOLUTION; PLAQUE AB Histopathology forms the gold standard for cancer diagnosis and therapy, and generally relies on manual examination of microscopic structural morphology within tissue. Fourier-Transform Infrared (FT-IR) imaging is an emerging vibrational spectroscopic imaging technique, especially in a High-Definition (HD) format, that provides the spatial specificity of microscopy at magnifications used in diagnostic surgical pathology. While it has been shown for standard imaging that IR absorption by tissue creates a strong signal where the spectrum at each pixel is a quantitative "fingerprint" of the molecular composition of the sample, here we show that this fingerprint also enables direct digital pathology without the need for stains or dyes for HD imaging. An assessment of the potential of HD imaging to improve diagnostic pathology accuracy is presented. C1 [Wrobel, Tomasz P.; Bhargava, Rohit] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. [Kwak, Jin Tae] NIH, Ctr Intervent Oncol, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Kadjacsy-Balla, Andre] Univ Illinois, Dept Pathol, Chicago, IL USA. [Kadjacsy-Balla, Andre; Bhargava, Rohit] Univ Illinois, Ctr Canc, Chicago, IL 60680 USA. [Bhargava, Rohit] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. RP Wrobel, TP (reprint author), Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. OI Bhargava, Rohit/0000-0001-7360-994X NR 18 TC 2 Z9 2 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0026-3 J9 PROC SPIE PY 2016 VL 9791 AR 97911D DI 10.1117/12.2217341 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BF7MT UT WOS:000384248300042 ER PT J AU Keil, MF Briassoulis, G Stratakis, CA AF Keil, Margaret F. Briassoulis, George Stratakis, Constantine A. TI The Role of Protein Kinase A in Anxiety Behaviors SO NEUROENDOCRINOLOGY LA English DT Article DE Protein kinase A; Anxiety; Behavioral phenotype; Amygdala ID RESPONSE ELEMENT-BINDING; CORTICOTROPIN-RELEASING-FACTOR; LONG-TERM POTENTIATION; POSTTRAUMATIC-STRESS-DISORDER; MEDIAL PREFRONTAL CORTEX; ALPHA REGULATORY SUBUNIT; KNOCK-OUT MICE; BENZODIAZEPINE RECEPTOR-BINDING; CYCLIC-AMP PHOSPHODIESTERASE; BIPOLAR AFFECTIVE-DISORDER AB This review focuses on the genetic and other evidence supporting the notion that the cyclic AMP (cAMP) signaling pathway and its mediator, the protein kinase A (PKA) enzyme, which respond to environmental stressors and regulate stress responses, are central to the pathogenesis of disorders related to anxiety. We describe the PKA pathway and review in vitro animal studies (mouse) and other evidence that support the importance of PKA in regulating behaviors that lead to anxiety. Since cAMP signaling and PKA have been pharmacologically exploited since the 1940s (even before the identification of cAMP as a second messenger with PKA as its mediator) for a number of disorders from asthma to cardiovascular diseases, there is ample opportunity to develop therapies using this new knowledge about cAMP, PKA, and anxiety disorders. (C) 2016 S. Karger AG, Basel C1 [Keil, Margaret F.; Briassoulis, George; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. [Briassoulis, George] Univ Crete, Dept Pediat Intens Care, Iraklion, Greece. RP Keil, MF; Stratakis, CA (reprint author), NICHD, NIH, SEGEN, 10 Ctr Dr,Bldg 10 CRC,Room 1 E3330, Bethesda, MD 20892 USA. EM keilm@mail.nih.gov; stratakc@mail.nih.gov NR 196 TC 0 Z9 0 U1 5 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2016 VL 103 IS 6 BP 625 EP 639 DI 10.1159/000414880 PG 15 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA DX6TV UT WOS:000384516900001 PM 26939049 ER PT J AU Ocampo, J Cui, F Zhurkin, VB Clark, DJ AF Ocampo, Josefina Cui, Feng Zhurkin, Victor B. Clark, David J. TI The proto-chromatosome: A fundamental subunit of chromatin? SO NUCLEUS LA English DT Article DE chromatin folding; chromatosome; linker histone; MNase-Exo-seq; Mnase-seq; nucleosome mapping; nucleosome; proto-chromatosome ID NUCLEOSOME CORE PARTICLE; LINKER DNA; ANGSTROM RESOLUTION; HISTONE; FIBER; YEAST; GENOME; GENES; ORGANIZATION; ACTIVATION AB Eukaryotic DNA is packaged into regularly spaced nucleosomes, resembling beads on a string. Each bead contains similar to 147 bp wrapped around a core histone octamer. Linker histone (H1) binds to the linker DNA to drive chromatin folding. Micrococcal nuclease (MNase) digestion studies reveal 2 mono-nucleosomal intermediates: the core particle (similar to 147 bp) and the chromatosome (similar to 160 bp; a core particle with additional DNA protected by H1). We have recently developed an improved method for mapping nucleosomes, using exonuclease III to remove residual linker (MNase-Exoseq). 1 We discovered 2 new intermediate particles corresponding to core particles with similar to 7 bp of linker protruding from one side (similar to 154 bp) or both sides (similar to 161 bp), which are formed in the absence of H1. We propose that these "proto-chromatosomes" are stabilized by core histone-DNA contacts in the linker, similar to 7 bp from the nucleosome boundaries. These contacts may determine the topography of the H1 binding site. C1 [Ocampo, Josefina; Clark, David J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Dev Biol, NIH, Bethesda, MD 20892 USA. [Cui, Feng] Rochester Inst Technol, Thomas H Gosnell Sch Life Sci, Rochester, NY 14623 USA. [Zhurkin, Victor B.] NCI, NIH, Bethesda, MD 20892 USA. RP Clark, DJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Dev Biol, NIH, Bethesda, MD 20892 USA.; Zhurkin, VB (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM zhurkin@nih.gov; clarkda@mail.nih.gov FU Intramural Research Program of the National Institutes of Health (NICHD); Intramural Research Program of the National Institutes of Health (NCI); National Institute of General Medical Sciences [R15GM116102] FX This work was funded by the Intramural Research Program of the National Institutes of Health (NICHD and NCI) and by a grant from the National Institute of General Medical Sciences (R15GM116102 to FC). NR 30 TC 0 Z9 0 U1 2 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1949-1034 EI 1949-1042 J9 NUCLEUS-PHILA JI Nucleus PY 2016 VL 7 IS 4 BP 382 EP 387 DI 10.1080/19491034.2016.1220466 PG 6 WC Cell Biology SC Cell Biology GA DX5ST UT WOS:000384442800007 PM 27645053 ER PT J AU Shan, LL Shan, X Zhang, T Zhai, KF Gao, GZ Chen, XY Gu, YQ AF Shan, Lingling Shan, Xin Zhang, Tinging Zhai, Kefeng Gao, Guizhen Chen, XiaoYuan Gu, Yueqing TI Transferrin-conjugated paclitaxel prodrugs for targeted cancer therapy SO RSC ADVANCES LA English DT Article ID LOADED NANOPARTICLES; BREAST-CANCER; DELIVERY; CHEMOTHERAPY; FORMULATION; TECHNOLOGY; EFFICACY AB Paclitaxel (PTX) is one of the most effective chemotherapeutic drugs ever developed and is effective against a wide spectrum of tumors. The clinical application of PTX, however, is limited by its severe side effects. We developed new ligand-mediated prodrugs, namely, PTX conjugated with Fmoc-L-glutamic acid 5-tert-butyl ester (linker) and transferrin (Tf, ligand/carriers), to specifically target tumor cells/tissues. PTX was labeled with FITC or a near-infrared (NIR) dye ICG-Der-02, respectively, for in vitro and in vivo imaging studies. MTT assay and apoptosis studies demonstrated that the prodrug had efficient inhibition of tumor cell proliferation with low toxicity to normal cells. More importantly, the prodrug Tf-Glu-PTX displayed a potential to overcome PTX resistance in drug-resistant MDA-MB-231 cell lines. Our in vivo studies also demonstrated that Tf-Glu-PTX significantly decreased side effects and enhanced the antitumor efficiency compared to free PTX. Collectively, our study showed that Tf-Glu-PTX is a promising prodrug for targeted cancer therapy. C1 [Shan, Lingling; Shan, Xin; Zhang, Tinging; Zhai, Kefeng; Gao, Guizhen] Suzhou Univ, Sch Biol & Food Engn, Sch Continuing Educ, Inst Pharmaceut Biotechnol, Suzhou 234000, Peoples R China. [Gu, Yueqing] China Pharmaceut Univ, Sch Life Sci & Technol, State Key Lab Nat Med, Dept Biomed Engn, Nanjing 210009, Jiangsu, Peoples R China. [Shan, Lingling; Chen, XiaoYuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Shan, LL (reprint author), Suzhou Univ, Sch Biol & Food Engn, Sch Continuing Educ, Inst Pharmaceut Biotechnol, Suzhou 234000, Peoples R China.; Gu, YQ (reprint author), China Pharmaceut Univ, Sch Life Sci & Technol, State Key Lab Nat Med, Dept Biomed Engn, Nanjing 210009, Jiangsu, Peoples R China.; Shan, LL (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM ntlinger-300@163.com FU Education Department of Anhui Province [gxfxZD2016266]; Key project of Anhui Educational Committee [KJ2014A249, KJ2015A220]; Quality Project of AnHui Education Department - The plan of "ChuangKe" laboratory [2015ckjh109] FX The authors are grateful to Natural Science Foundation Committee of China (NSFC81220108012, 661335007, 81171395 and 81328012), China Scholarship Council (201608340040), Program of Study Abroad for Young Scholar sponsored by Education Department of Anhui Province (gxfxZD2016266), and Key project of Anhui Educational Committee (KJ2014A249, KJ2015A220), and Quality Project of AnHui Education Department - The plan of "ChuangKe" laboratory (2015ckjh109). The Scientific Research Platform of Suzhou University (2015ykf15). NR 35 TC 0 Z9 0 U1 5 U2 5 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2046-2069 J9 RSC ADV JI RSC Adv. PY 2016 VL 6 IS 81 BP 77987 EP 77998 DI 10.1039/c6ra15141h PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA DU8RR UT WOS:000382482200097 ER PT J AU Break, TJ Hoffman, KW Swamydas, M Lee, CCR Lim, JK Lionakis, MS AF Break, Timothy J. Hoffman, Kevin W. Swamydas, Muthulekha Lee, Chyi-Chia Richard Lim, Jean K. Lionakis, Michail S. TI Batf3-dependent CD103(+) dendritic cell accumulation is dispensable for mucosal and systemic antifungal host defense SO VIRULENCE LA English DT Article DE Batf3; CD103; dendritic cells; fungal infection; IL-12; innate immunity; oropharyngeal candidiasis; systemic candidiasis ID CANDIDA-ALBICANS; OROPHARYNGEAL CANDIDIASIS; INFECTION; IMMUNODEFICIENCY; IMMUNITY; SUBSETS; POINT; MODEL; IL-12; BATF3 AB Dendritic cells (DCs) are critical for defense against a variety of pathogens and the formation of adaptive immune responses. The transcription factor Batf3 is critical for the development of CD103(+)CD11b(-) DCs, which promote IL-12-dependent protective immunity during viral and parasitic infections, dampen Th2 immunity during helminthic infection, and exert detrimental effects during bacterial infection. Whether CD103(+) DCs modulate immunity during systemic or mucosal fungal disease remains unknown. Herein, we report that Batf3 is critical for accumulation of CD103(+) DCs in the kidney and tongue at steady state, for their expansion during systemic and oropharyngeal candidiasis, and for tissue-specific production of IL-12 in kidney but not tongue during systemic and oropharyngeal candidiasis, respectively. Importantly, deficiency of CD103(+) DCs does not impair survival or fungal clearance during systemic or oropharyngeal candidiasis, indicating that Batf3-dependent CD103(+) DC accumulation mediates pathogen- and tissue-specific immune effects. C1 [Break, Timothy J.; Swamydas, Muthulekha; Lionakis, Michail S.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Hoffman, Kevin W.; Lim, Jean K.] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA. [Lee, Chyi-Chia Richard] NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Lionakis, MS (reprint author), NIAID, 9000 Rockville Pike,Bldg 10,Room 11C102, Bethesda, MD 20892 USA. EM lionakism@mail.nih.gov FU Intramural Research Program of the NIH, NIAID; NIH [1R01AI108715] FX This work was supported in part by the Intramural Research Program of the NIH, NIAID. JKL was supported by NIH grant 1R01AI108715. NR 33 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2150-5594 EI 2150-5608 J9 VIRULENCE JI Virulence PY 2016 VL 7 IS 7 BP 826 EP 835 DI 10.1080/21505594.2016.1186324 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DX0BJ UT WOS:000384026200014 PM 27191829 ER PT J AU Zaravinos, A Chen, LY Zi, Z Dose, M Caridha, R Ren, WC Casellas, R Pan-Hammarstrom, Q AF Zaravinos, Anostolos Chen, Longyun Zi, Zhang Dose, Marei Caridha, Rozina Ren, Weicheng Casellas, Rafael Pan-Hammarstrom, Qiang TI Next-generation sequencing approaches highlight the genetic events that drive B-cell lymphomagenesis SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Zaravinos, Anostolos; Caridha, Rozina; Ren, Weicheng; Pan-Hammarstrom, Qiang] Karolinska Inst, Dept Lab Med, Div Clin Immunol, SE-14186 Stockholm, Sweden. [Zaravinos, Anostolos] European Univ Cyprus, Sch Sci, Dept Life Sci, CY-1516 Nicosia, Cyprus. [Chen, Longyun; Zi, Zhang] Beijing Genom Inst, Shenzhen 518083, Guangdong, Peoples R China. [Dose, Marei; Casellas, Rafael] NIAMS, Genom & Immun, NIH, Bethesda, MD 20892 USA. [Dose, Marei; Casellas, Rafael] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM A.Zaravinos@euc.ac.cy NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PY 2016 VL 38 SU 1 MA 111 BP S7 EP S7 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DW6CC UT WOS:000383733000012 ER PT J AU Danforth, DN AF Danforth, David N., Jr. TI Genomic Changes in Normal Breast Tissue in Women at Normal Risk or at High Risk for Breast Cancer SO BREAST CANCER-BASIC AND CLINICAL RESEARCH LA English DT Article DE breast cancer; breast cancer risk; normal breast tissue; carcinogenic pathway; cancerized fields; preneoplastic breast tissue ID MAMMARY EPITHELIAL-CELLS; ESTROGEN-RECEPTOR-BETA; IN-SITU HYBRIDIZATION; EPIDERMAL-GROWTH-FACTOR; NUCLEAR-DNA CONTENT; TELOMERASE REVERSE-TRANSCRIPTASE; GENE PROMOTER HYPERMETHYLATION; P53 PROTEIN ACCUMULATION; METHYLATION-SPECIFIC PCR; TUMOR-SUPPRESSOR GENES AB Sporadic breast cancer develops through the accumulation of molecular abnormalities in normal breast tissue, resulting from exposure to estrogens and other carcinogens beginning at adolescence and continuing throughout life. These molecular changes may take a variety of forms, including numerical and structural chromosomal abnormalities, epigenetic changes, and gene expression alterations. To characterize these abnormalities, a review of the literature has been conducted to define the molecular changes in each of the above major genomic categories in normal breast tissue considered to be either at normal risk or at high risk for sporadic breast cancer. This review indicates that normal risk breast tissues (such as reduction mammoplasty) contain evidence of early breast carcinogenesis including loss of heterozygosity, DNA methylation of tumor suppressor and other genes, and telomere shortening. In normal tissues at high risk for breast cancer (such as normal breast tissue adjacent to breast cancer or the contralateral breast), these changes persist, and are increased and accompanied by aneuploidy, increased genomic instability, a wide range of gene expression differences, development of large cancerized fields, and increased proliferation. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. A model for the breast carcinogenic pathway in normal risk and high-risk breast tissues is proposed. These findings should clarify our understanding of breast carcinogenesis in normal breast tissue and promote development of improved methods for risk assessment and breast cancer prevention in women. C1 [Danforth, David N., Jr.] NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Danforth, DN (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM david_danforth@nih.gov NR 308 TC 1 Z9 1 U1 1 U2 1 PU LIBERTAS ACAD PI AUCKLAND PA PO BOX 300-874, ALBANY 0752, AUCKLAND, 00000, NEW ZEALAND SN 1178-2234 J9 BREAST CANCER-BASIC JI Breast Cancer-Basic Clin. Res. PY 2016 VL 10 BP 109 EP 146 DI 10.4137/BCBCR.S39384 PG 38 WC Oncology SC Oncology GA DW9EJ UT WOS:000383958500008 PM 27559297 ER PT S AU Shin, DM Son, A Park, S Kim, MS Ahuja, M Muallem, S AF Shin, Dong Min Son, Aran Park, Seonghee Kim, Min Seuk Ahuja, Malini Muallem, Shmuel BE Rosado, JA TI The TRPCs, Orais and STIMs in ER/PM Junctions SO CALCIUM ENTRY PATHWAYS IN NON-EXCITABLE CELLS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE TRPC channels; STIM1; STIM2; Orai; ER/PM junction ID STROMAL INTERACTION MOLECULE-1; OPERATED CALCIUM-ENTRY; MEMBRANE CONTACT SITES; FAST CA2+-DEPENDENT INACTIVATION; ENDOPLASMIC-RETICULUM; PLASMA-MEMBRANE; CA2+ ENTRY; CHANNEL FUNCTION; CRAC CHANNELS; MECHANISTIC INSIGHTS AB The Ca2+ second messenger is initiated at ER/PM junctions and propagates into the cell interior to convey the receptor information. The signal is maintained by Ca2+ influx across the plasma membrane through the Orai and TRPC channels. These Ca2+ influx channels form complexes at ER/PM junctions with the ER Ca2+ sensor STIM1, which activates the channels. The function of STIM1 is modulated by other STIM isoforms like STIM1L, STIM2 and STIM2.1/STIM2 beta and by SARAF, which mediates the Ca2+-dependent inhibition of Orai channels. The ER/PM junctions are formed at membrane contact sites by tethering proteins that generate several types of ER/PM junctions, such as PI(4,5)P-2-poor and PI(4,5)P-2-rich domains. This chapter discusses several properties of the TRPC channels, the Orai channels and the STIMs, their key interacting proteins and how interaction of the STIMs with the channels gates their activity. The chapter closes by highlighting open questions and potential future directions in this field. C1 [Shin, Dong Min] Yonsei Univ, Coll Dent, BK PLUS Project 21, Dept Oral Biol, Seoul 120752, South Korea. [Son, Aran; Ahuja, Malini; Muallem, Shmuel] Natl Inst Dent & Craniofacial Res, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Park, Seonghee] Ewha Womans Univ, Sch Med, Dept Physiol, 911-1 Mok 6 Dong, Seoul 158710, South Korea. [Kim, Min Seuk] Wonkwang Univ, Sch Dent, Dept Oral Physiol, Iksan, Jeonbuk, South Korea. RP Shin, DM (reprint author), Yonsei Univ, Coll Dent, BK PLUS Project 21, Dept Oral Biol, Seoul 120752, South Korea.; Muallem, S (reprint author), Natl Inst Dent & Craniofacial Res, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. EM dmshin@yuhs.ac; Shmuel.muallem@nih.gov NR 132 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0065-2598 BN 978-3-319-26974-0; 978-3-319-26972-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2016 VL 898 BP 47 EP 66 DI 10.1007/978-3-319-26974-0_3 D2 10.1007/978-3-319-26974-0 PG 20 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA BF6PP UT WOS:000383508600004 PM 27161224 ER PT S AU Ong, HL de Souza, LB Ambudkar, IS AF Ong, Hwei Ling de Souza, Lorena Brito Ambudkar, Indu S. BE Rosado, JA TI Role of TRPC Channels in Store-Operated Calcium Entry SO CALCIUM ENTRY PATHWAYS IN NON-EXCITABLE CELLS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE TRPC channels; SOCE; Trafficking; Function ID CAPACITATIVE CA2+ ENTRY; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; SALIVARY-GLAND CELLS; SMOOTH-MUSCLE-CELLS; HETEROMERIC TRPV4-C1 CHANNELS; PLASMA-MEMBRANE LOCALIZATION; INTERACTION MOLECULE-1 STIM1; NONSELECTIVE CATION CHANNEL; GLOMERULAR MESANGIAL CELLS; LIPID RAFT DOMAINS AB Store-operated calcium entry (SOCE) is a ubiquitous Ca2+ entry pathway that is activated in response to depletion of Ca2+ stores within the endoplasmic reticulum (ER) and contributes to the control of various physiological functions in a wide variety of cell types. The transient receptor potential canonical (TRPC) channels (TRPCs 1-7), that are activated by stimuli leading to PIP 2 hydrolysis, were first identified as molecular components of SOCE channels. TRPC channels show a miscellany of tissue expression, physiological functions and channel properties. However, none of the TRPC members display currents that resemble I CRAC. Intensive search for the CRAC channel component led to identification of Orai1 and STIM1, now established as being the primary constituents of the CRAC channel. There is now considerable evidence that STIM1 activates both Orai1 and TRPC1 via distinct domains in its C-terminus. Intriguingly, TRPC1 function is not only dependent on STIM1 but also requires Orai1. The critical functional interaction between TRPC1 and Orai1, which determines the activation of TRPC1, has also been identified. In this review, we will discuss current concepts regarding the role of TRPC channels in SOCE, the physiological functions regulated by TRPC-mediated SOCE, and the complex mechanisms underlying the regulation of TRPCs, including the functional interactions with Orai1 and STIM1. C1 [Ong, Hwei Ling; de Souza, Lorena Brito; Ambudkar, Indu S.] Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, NIH, Bldg 10,Room 1N-113, Bethesda, MD 20892 USA. RP Ong, HL; Ambudkar, IS (reprint author), Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, NIH, Bldg 10,Room 1N-113, Bethesda, MD 20892 USA. EM ongh@mail.nih.gov; indu.ambudkar@nih.gov FU Intramural NIH HHS NR 153 TC 4 Z9 4 U1 2 U2 2 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0065-2598 BN 978-3-319-26974-0; 978-3-319-26972-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2016 VL 898 BP 87 EP 109 DI 10.1007/978-3-319-26974-0_5 D2 10.1007/978-3-319-26974-0 PG 23 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA BF6PP UT WOS:000383508600006 PM 27161226 ER PT J AU Mullooly, M McGowan, PM Crown, J Duffy, MJ AF Mullooly, Maeve McGowan, Patricia M. Crown, John Duffy, Michael J. TI The ADAMs family of proteases as targets for the treatment of cancer SO CANCER BIOLOGY & THERAPY LA English DT Review DE ADAMs; cancer; therapy; inhibitors; ADAM17; ADAM10 ID ALPHA-CONVERTING-ENZYME; NECROSIS-FACTOR-ALPHA; INTERLEUKIN-6 RECEPTOR; DISINTEGRIN; DOMAIN AB The ADAMs (a disintegrin and metalloproteases) are transmembrane multidomain proteins implicated in multiple biological processes including proteolysis, cell adhesion, cell fusion, cell proliferation and cell migration. Of these varied activities, the best studied is their role in proteolysis. However, of the 22 ADAMs believed to be functional in humans, only approximately a half possess matrix metalloproteinase (MMP)-like protease activity. In contrast to MMPs which are mostly implicated in the degradation of extracellular matrix proteins, the main ADAM substrates are the ectodomains of type I and type II transmembrane proteins. These include growth factor/cytokine precursors, growth factor/cytokine receptors and adhesion proteins. Recently, several different ADAMs, especially ADAM17, have been shown to play a role in the development and progression of multiple cancer types. Consistent with this role in cancer, targeting ADAM17 with either low molecular weight inhibitors or monoclonal antibodies was shown to have anti-cancer activity in multiple preclinical systems. Although early phase clinical trials have shown no serious side effects with a dual ADAM10/17 low molecular weight inhibitor, the consequences of long-term treatment with these agents is unknown. Furthermore, efficacy in clinical trials remains to be shown. C1 [Mullooly, Maeve] NIH, Bldg 10, Bethesda, MD 20892 USA. [Mullooly, Maeve; McGowan, Patricia M.; Duffy, Michael J.] Univ Coll Dublin, UCD Sch Med & Med Sci, Conway Inst Biomol & Biomed Res, Dublin, Ireland. [McGowan, Patricia M.] St Vincents Univ Hosp, Educ & Res Ctr, Dublin, Ireland. [Crown, John] St Vincents Univ Hosp, Dept Med Oncol, Dublin, Ireland. [Duffy, Michael J.] St Vincents Univ Hosp, UCD Clin Res Ctr, Dublin, Ireland. RP Duffy, MJ (reprint author), St Vincents Univ Hosp, Clin Res Ctr, Elm Pk, Dublin, Ireland. EM Michael.J.Duffy@ucd.ie FU Science Foundation Ireland; Strategic Research Cluster Award [08/SRC/B1410]; BREAST-PREDICT program of the Irish Cancer Society [CCRC13GAL]; Cancer Clinical Research Trust FX The authors wish to thank Science Foundation Ireland, Strategic Research Cluster Award (08/SRC/B1410) to Molecular Therapeutics for Cancer Ireland (MTCI)/National Cancer Research Center in Ireland (NCRCI), the BREAST-PREDICT (CCRC13GAL) program of the Irish Cancer Society and the Cancer Clinical Research Trust for funding this work. The opinions, findings and conclusions or recommendations expressed in this article however, are those of the relevant authors and do not necessarily reflect the views of the funding organizations. NR 18 TC 3 Z9 3 U1 3 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PY 2016 VL 17 IS 8 BP 870 EP 880 DI 10.1080/15384047.2016.1177684 PG 11 WC Oncology SC Oncology GA DW1ZY UT WOS:000383443900010 PM 27115328 ER PT J AU Chang, LC Das, B Lih, CJ Si, H Camalier, CE McGregor, PM Polley, E AF Chang, Lun-Ching Das, Biswajit Lih, Chih-Jian Si, Han Camalier, Corinne E. McGregor, Paul M., III Polley, Eric TI RefCNV: Identification of Gene-Based Copy Number Variants Using Whole Exome Sequencing SO CANCER INFORMATICS LA English DT Article DE next-generation sequencing; whole exome sequencing; copy number variation; methodology ID COMPARATIVE GENOMIC HYBRIDIZATION; BREAST-CANCER; GROWTH; CELLS; SNP AB With rapid advances in DNA sequencing technologies, whole exome sequencing (WES) has become a popular approach for detecting somatic mutations in oncology studies. The initial intent of WES was to characterize single nucleotide variants, but it was observed that the number of sequencing reads that mapped to a genomic region correlated with the DNA copy number variants (CNVs). We propose a method RefCNV that uses a reference set to estimate the distribution of the coverage for each exon. The construction of the reference set includes an evaluation of the sources of variability in the coverage distribution. We observed that the processing steps had an impact on the coverage distribution. For each exon, we compared the observed coverage with the expected normal coverage. Thresholds for determining CNVs were selected to control the false-positive error rate. RefCNV prediction correlated significantly (r = 0.96-0.86) with CNV measured by digital polymerase chain reaction for MET (7q31), EGFR (7p12), or ERBB2 (17q12) in 13 tumor cell lines. The genome-wide CNV analysis showed a good overall correlation (Spearman's coefficient = 0.82) between RefCNV estimation and publicly available CNV data in Cancer Cell Line Encyclopedia. RefCNV also showed better performance than three other CNV estimation methods in genome-wide CNV analysis. C1 [Chang, Lun-Ching; Polley, Eric] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Das, Biswajit; Lih, Chih-Jian; Si, Han; Camalier, Corinne E.; McGregor, Paul M., III] Leidos Biomed Res Inc, Mol Characterizat & Clin Assay Dev Lab, Frederick Natl Lab Canc Res, Frederick, MD USA. RP Polley, E (reprint author), NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. EM eric.polley@nih.gov NR 23 TC 0 Z9 0 U1 1 U2 1 PU LIBERTAS ACAD PI AUCKLAND PA PO BOX 300-874, ALBANY 0752, AUCKLAND, 00000, NEW ZEALAND SN 1176-9351 J9 CANCER INFORM JI Cancer Inform. PY 2016 VL 15 BP 65 EP 71 DI 10.4137/CIN.S36612 PG 7 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA DW9HK UT WOS:000383967400003 PM 27147817 ER PT S AU Wang, PH De Sancho, D Best, RB Blumberger, J AF Wang, P. -H. De Sancho, D. Best, R. B. Blumberger, J. BE Voth, GA TI Computation of Rate Constants for Diffusion of Small Ligands to and from Buried Protein Active Sites SO COMPUTATIONAL APPROACHES FOR STUDYING ENZYME MECHANISM, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID X-RAY CRYSTALLOGRAPHY; DEHYDROGENASE/ACETYL-COA SYNTHASE; MOLECULAR-DYNAMICS SIMULATIONS; MARKOV STATE MODELS; MIGRATION PATHWAYS; GAS-DIFFUSION; MYOGLOBIN; O-2; BINDING; H-2 AB The diffusion of ligands to actives sites of proteins is essential to enzyme catalysis and many cellular signaling processes. In this contribution we review our recently developed methodology for calculation of rate constants for diffusion and binding of small molecules to buried protein active sites. The diffusive dynamics of the ligand obtained from molecular dynamics simulation is coarse grained and described by a Markov state model. Diffusion and binding rate constants are then obtained either from the reactive flux formalism or by fitting the time-dependent population of the Markov state model to a phenomenological rate law. The method is illustrated by applications to diffusion of substrate and inhibitors in [NiFe] hydrogenase, CO-dehydrogenase, and myoglobin. We also discuss a recently developed sensitivity analysis that allows one to identify hot spots in proteins, where mutations are expected to have the strongest effects on ligand diffusion rates. C1 [Wang, P. -H.] RIKEN Theoret Mol Sci Lab, Wako, Saitama, Japan. [De Sancho, D.] CIC NanoGUNE, Donostia San Sebastian, Spain. [De Sancho, D.] Ikerbasque, Basque Fdn Sci, Bilbao, Spain. [Best, R. B.] Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD USA. [Blumberger, J.] UCL, London, England. RP Blumberger, J (reprint author), UCL, London, England. EM j.blumberger@ucl.ac.uk RI De Sancho, David/C-4995-2009; nanoGUNE, CIC/A-2623-2015 OI De Sancho, David/0000-0002-8985-2685; NR 45 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-811108-6; 978-0-12-811107-9 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2016 VL 578 BP 299 EP 326 DI 10.1016/bs.mie.2016.05.039 PG 28 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA BF7BL UT WOS:000383908000014 PM 27497172 ER PT S AU Montgomery, DC Meier, JL AF Montgomery, D. C. Meier, J. L. BE Marmorstein, R TI Mapping Lysine Acetyltransferase-Ligand Interactions by Activity-Based Capture SO ENZYMES OF EPIGENETICS, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID TRANSCRIPTIONAL COACTIVATOR; HISTONE ACETYLTRANSFERASES; PROTEIN ACETYLATION; INHIBITORS; MUTATIONS; PROTEOMICS; COMPLEXES; TOOLS; ACIDS; P300 AB Changes in reversible protein acetylation mediate many key aspects of genomic regulation and enzyme function. The catalysts for this posttranslational modification, lysine acetyltransferases (KATs), have been difficult targets for characterization due to their complex architecture and challenging reconstitution. To address this challenge, here we describe methods to profile endogenous KAT activities using activity-based probes. This method facilitates the targeted analysis of several cellular KATs and can be used to study their interactions with many different types of ligands, including acyl-CoA metabolites. This competitive activity-based capture approach provides a method to assess the selectivity of ligands for different KAT families in complex proteomic settings, and thus has the potential to offer substantial insights into the regulation of cellular KAT function. C1 [Montgomery, D. C.; Meier, J. L.] NCI, Biol Chem Lab, Frederick, MD 21701 USA. RP Meier, JL (reprint author), NCI, Biol Chem Lab, Frederick, MD 21701 USA. EM jordan.meier@nih.gov NR 32 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-811902-0; 978-0-12-805381-2 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2016 VL 574 BP 105 EP 123 DI 10.1016/bs.mie.2016.01.006 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BF6OD UT WOS:000383370500006 PM 27423859 ER PT J AU Basudhar, D Somasundaram, V Glynn, S Ridnour, LA Cheng, RY Wink, DA AF Basudhar, Debashree Somasundaram, Veena Glynn, Sharon Ridnour, Lisa A. Cheng, Robert Y. Wink, David A. TI Regulatory effects of NOS2-COX2 in breast cancer progression in tumor microenvironment SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Basudhar, Debashree; Somasundaram, Veena; Glynn, Sharon; Ridnour, Lisa A.; Cheng, Robert Y.; Wink, David A.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. [Glynn, Sharon] Natl Univ Ireland Galway, Prostate Canc Inst, Galway, Ireland. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PY 2016 VL 38 SU 1 MA 408 BP S81 EP S81 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DW6CC UT WOS:000383733000309 ER PT J AU Cherukuri, MK AF Cherukuri, Murali Krishna TI MRI- and EPR-based imaging biomarkers to guide treatment in tumor-bearing mice SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Cherukuri, Murali Krishna] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PY 2016 VL 38 SU 1 MA 410 BP S82 EP S82 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DW6CC UT WOS:000383733000311 ER PT J AU Gillet, JP Sana, G Madigan, JP Gartner, JJ Lin, CH Fourrez, M Shukla, S Ambudkar, SV Rutledge, RM Xia, D Rosenberg, SA Gottesman, MM Samuels, Y AF Gillet, Jean-Pierre Sana, Geraldine Madigan, James P. Gartner, Jared J. Lin, Cheng-Ho Fourrez, Marie Shukla, Suneet Ambudkar, Suresh V. Rutledge, Robert M. Xia, Di Rosenberg, Steven A. Gottesman, Michael M. Samuels, Yardena TI The multifaceted ABCB5 transporter: Spotlight on its role in tumorigenesis SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Gillet, Jean-Pierre; Sana, Geraldine; Fourrez, Marie] Univ Namur, Fac Medmine, Namur Res Inst Life Sci NARILIS, Lab Mol Canc Biol, Namur, Belgium. [Madigan, James P.; Shukla, Suneet; Ambudkar, Suresh V.; Rutledge, Robert M.; Xia, Di; Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. [Gartner, Jared J.; Samuels, Yardena] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Lin, Cheng-Ho] Rare Genom Inst, St Louis, MO USA. [Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Samuels, Yardena] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. EM jean.pierre.gillet@unamur.be NR 0 TC 0 Z9 0 U1 2 U2 2 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PY 2016 VL 38 SU 1 MA 114 BP S8 EP S8 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DW6CC UT WOS:000383733000015 ER PT J AU Margolin, G Petrykowska, HM Jameel, N Bell, DW Young, AC Elnitski, L AF Margolin, Gennady Petrykowska, Hanna M. Jameel, Nader Bell, Daphne W. Young, Alice C. Elnitski, Laura TI Assessing ZNF154 hypermethylation from circulating tumor DNA in pan-cancer diagnostics SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Margolin, Gennady; Petrykowska, Hanna M.; Jameel, Nader; Elnitski, Laura] Translat & Funct Genom Branch, Rockville, MD 20852 USA. [Bell, Daphne W.] Canc Genet & Comparat Genom Branch, Bethesda, MD 20892 USA. [Young, Alice C.] NIH, Intramural Sequencing Ctr, Rockville, MD 20852 USA. [Margolin, Gennady; Petrykowska, Hanna M.; Jameel, Nader; Bell, Daphne W.; Young, Alice C.; Elnitski, Laura] NHGRI, Bethesda, MD 20894 USA. EM elnitski@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PY 2016 VL 38 SU 1 MA 251 BP S42 EP S42 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DW6CC UT WOS:000383733000152 ER PT J AU Somasundaram, V Basudhar, D Ridnour, LA Cheng, R Wink, DA AF Somasundaram, Veena Basudhar, Debashree Ridnour, Lisa A. Cheng, Robert Wink, David A. TI Varied immune modulatory effects of reactive nitrogen oxide species in tumor associated myeloid cells SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Somasundaram, Veena; Basudhar, Debashree; Ridnour, Lisa A.; Cheng, Robert; Wink, David A.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. EM veena.somasundaram@nih.gov; wink@mail.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PY 2016 VL 38 SU 1 MA 267 BP S46 EP S46 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DW6CC UT WOS:000383733000168 ER PT J AU Mak, MKY Cheung, V Ma, SY Lu, ZL Wang, DF Lou, WT Shi, L Mok, VCT Chu, WCW Hallett, M AF Mak, Margaret K. Y. Cheung, Vinci Ma, Shuangye Lu, Zhong L. Wang, Defeng Lou, Wutao Shi, Lin Mok, Vincent C. T. Chu, Winnie C. W. Hallett, Mark TI Increased Cognitive Control During Execution of Finger Tap Movement in People with Parkinson's Disease SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Cerebellum; cognition; fMRI; movement disorders; Parkinson's disease ID EXTERNALLY TRIGGERED MOVEMENTS; STATE FUNCTIONAL CONNECTIVITY; BASAL GANGLIA; MOTOR CORTEX; CEREBELLUM; FMRI; PET; ACTIVATION; HAND; GAIT AB Background: Previous studies employed demanding and complex hand tasks to study the brain activation in people with Parkinson's Disease (PD). There is inconsistent finding about the cerebellar activity during movement execution of this patient population. Objectives: This study aimed to examine the brain activation patterns of PD individuals in the on-state and healthy control subjects in a simple finger tapping task. Methods: Twenty-seven patients with PD and 22 age-matched healthy subjects were recruited for the study. Subjects were instructed to perform simple finger tapping tasks under self-and cue-initiated conditions in separate runs while their brain activations were captured using fMRI. Results: Healthy subjects had higher brain activity in contralateral precentral gyrus during the self-initiated task, and higher brain activity in the ipsilateral middle occipital gyrus during the cue-initiated task. PD patients had higher brain activity in the cerebellum Crus I (bilateral) and lobules VI (ipsilateral) during the self-initiated task and higher brain activity in the contralateral middle frontal gyrus during the cue-initiated task. When compared with healthy controls, PD patients had lower brain activity in the contralateral inferior parietal lobule during the self-initiated task, and lower brain activity in the ipsilateral cerebellum lobule VIII, lobule VIIB and vermis VIII, and thalamus during the cue-initiated task. Conjunction analysis indicated that both groups had activation in bilateral cerebellum and SMA and ipsilateral precentral gyrus and postcentral gyrus during both self-and cue-initiated movement. Individuals with PD exhibited higher brain activity in the executive zone (cerebellum Crus I and II) during self-initiated movement, and lower brain activity in the sensorimotor zone (i.e. lobule VIIb and VIII of the cerebellum) during cue-initiated movement. Discussions: The findings suggest that individuals with PD may use more executive control when performing simple movements. C1 [Mak, Margaret K. Y.; Ma, Shuangye] Hong Kong Polytech Univ, Dept Rehabil Sci, Hong Kong, Hong Kong, Peoples R China. [Cheung, Vinci] Shue Yan Univ, Dept Counselling & Psychol, Hong Kong, Hong Kong, Peoples R China. [Lu, Zhong L.] Ohio State Univ, Dept Psychol, Ctr Cognit & Behav Brain Imaging, Columbus, OH USA. [Wang, Defeng; Lou, Wutao; Chu, Winnie C. W.] Chinese Univ Hong Kong, Dept Imaging & Intervent Radiol, Hong Kong, Hong Kong, Peoples R China. [Shi, Lin; Mok, Vincent C. T.] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Mak, MKY (reprint author), Hong Kong Polytech Univ, Dept Rehabil Sci, Hong Kong, Hong Kong, Peoples R China. EM Margaret.Mak@polyu.edu.hk RI Chu, Winnie/F-8449-2014; Shi, Lin/K-5241-2014; Mok, Vincent /N-6421-2015 FU Research Grants Council of the Hong Kong Special Administrative Region, China [PolyU: 562212] FX The work described in this paper was by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. PolyU: 562212). NR 60 TC 0 Z9 0 U1 4 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 EI 1877-718X J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2016 VL 6 IS 3 BP 639 EP 650 DI 10.3233/JPD-160849 PG 12 WC Neurosciences SC Neurosciences & Neurology GA DW7AK UT WOS:000383803000019 PM 27372216 ER PT J AU He, C Yu, CR Mattapallil, MJ Sun, L Larkin, J Egwuagu, CE AF He, Chang Yu, Cheng-Rong Mattapallil, Mary J. Sun, Lin Larkin, Joseph, III Egwuagu, Charles E. TI SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis) SO MEDIATORS OF INFLAMMATION LA English DT Article ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; CYTOKINE SIGNALING SOCS; T-CELLS; OCULAR INFLAMMATION; RATS; PROLIFERATION; INDUCTION; PATHWAYS; PROTEINS; RETINA AB Uveitis is a potentially sight-threatening disease characterized by repeated cycles of remission and recurrent inflammation. The JAK/STAT pathway regulates the differentiation of pathogenic Th1 andTh17 cells that mediate uveitis. A SOCS1 mimetic peptide (SOCS1-KIR) that inhibits JAK2/STAT1 pathways has recently been shown to suppress experimental autoimmune uveitis (EAU). However, it is not clear whether SOCS1-KIR ameliorated uveitis by targeting JAK/STAT pathways of pathogenic lymphocytes or via inhibition of macrophages and antigen-presenting cells that also enter the retina during EAU. To further investigate mechanisms that mediate SOCS1-KIR effects and evaluate the efficacy of SOCS1-KIR as an investigational drug for chronic uveitis, we induced EAU in rats by adoptive transfer of uveitogenic T-cells and monitored disease progression and severity by slit-lamp microscopy, histology, and optical coherence tomography. Topical administration of SOCS1-KIR ameliorated acute and chronic posterior uveitis by inhibiting Th17 cells and the recruitment of inflammatory cells into retina while promoting expansion of IL-10-producing Tregs. We further show that SOCS1-KIR conferred protection of resident retinal cells that play critical role in vision from cytotoxic effects of inflammatory cytokines by down regulating proapoptotic genes. Thus, SOCS1-KIR suppresses uveitis and confers neuroprotective effects and might be exploited as a noninvasive treatment for chronic uveitis. C1 [He, Chang; Yu, Cheng-Rong; Sun, Lin; Egwuagu, Charles E.] NEI, Mol Immunol Sect, NIH, Bethesda, MD 20892 USA. [He, Chang] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China. [Mattapallil, Mary J.] NEI, Immunoregulat Sect, NIH, Bethesda, MD 20892 USA. [Larkin, Joseph, III] Univ Florida, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA. RP Egwuagu, CE (reprint author), NEI, Mol Immunol Sect, NIH, Bethesda, MD 20892 USA. EM egwuaguc@nei.nih.gov NR 30 TC 0 Z9 0 U1 5 U2 5 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 0962-9351 EI 1466-1861 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PY 2016 AR 2939370 DI 10.1155/2016/2939370 PG 15 WC Cell Biology; Immunology SC Cell Biology; Immunology GA DX1CU UT WOS:000384104000001 ER PT S AU Kong, LJ Tang, JY Cui, M AF Kong, Lingjie Tang, Jianyong Cui, Meng BE Periasamy, A So, PTC Konig, K TI In vivo imaging flow cytometry based on laser scanning two-photon microscopy at kHz cross-sectional frame rate SO MULTIPHOTON MICROSCOPY IN THE BIOMEDICAL SCIENCES XVI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Multiphoton Microscopy in the Biomedical Sciences XVI CY FEB 14-16, 2016 CL San Francisco, CA SP SPIE, Becker & Hickl GmbH, Carl Zeiss, Chroma Technol Corp, Coherent Inc, Semrock Inc, ISS Inc, JenLab GmbH, Leica Microsystems, Spectra Phys DE flow cytometry; multiphoton microscopy; deformability cytometry; biological dynamics; biomedical optics ID ADAPTIVE COMPENSATION TECHNIQUE; FLUORESCENCE MICROSCOPY; CELLS; TISSUE AB In vivo flow cytometry has found numerous applications in biology and pharmacology. However, conventional cytometry does not provide the detailed morphological information that is needed to fully determine the phenotype of individual circulating cells. Imaging cytometry, capable of visualizing the morphology and dynamics of the circulating cells at high spatiotemporal resolution, is highly desired. Current wide-field based image cytometers are limited in the imaging depth and provide only two-dimensional resolution. For deep tissue imaging, laser scanning two-photon fluorescence microscopy (TPM) is widely adopted. However, for applications in flow cytometry, the axial scanning speed of current TPMs is inadequate to provide high-speed cross-sectional imaging of vasculature. We have integrated an optical phase-locked ultrasound lens into a standard TPM and achieved microsecond-scale axial scanning. With a galvo scanner for transverse scanning, we achieved kHz cross-sectional frame rate. Here we report its applications for in vivo deformability cytometry and in vivo imaging flow cytometry, and demonstrate the capability of imaging dynamical morphologies of flowing cells, distinguishing cells and cellular clusters, and simultaneously quantifying different cell populations based on their fluorescent labels. C1 [Kong, Lingjie; Cui, Meng] Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. [Tang, Jianyong] NIAID, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Cui, Meng] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. [Cui, Meng] Purdue Univ, Integrated Imaging Cluster, W Lafayette, IN 47907 USA. [Cui, Meng] Purdue Univ, Bindley Biosci Ctr, W Lafayette, IN 47907 USA. RP Kong, LJ (reprint author), Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. EM kong52@purdue.edu RI kong, lingjie/G-5822-2012 OI kong, lingjie/0000-0003-1974-3245 NR 23 TC 0 Z9 0 U1 5 U2 5 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-946-7 J9 PROC SPIE PY 2016 VL 9712 AR 971203 DI 10.1117/12.2211418 PG 6 WC Engineering, Biomedical; Microscopy; Optics SC Engineering; Microscopy; Optics GA BF6XN UT WOS:000383762200003 ER PT B AU Kim, SYH AF Kim, Scott Y. H. BE Moseley, DD Gala, G TI The Place of Ability to Value in the Evaluation of Decision-Making Capacity SO PHILOSOPHY AND PSYCHIATRY: PROBLEMS, INTERSECTIONS, AND NEW PERSPECTIVES LA English DT Article; Book Chapter ID COMPETENCE C1 [Kim, Scott Y. H.] NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA. [Kim, Scott Y. H.] Univ Michigan, Ctr Bioeth & Behav Sci Med, Ann Arbor, MI 48109 USA. RP Kim, SYH (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-1-315-68872-5; 978-0-415-70816-6 PY 2016 BP 189 EP 203 PG 15 WC Philosophy; Psychiatry SC Philosophy; Psychiatry GA BF6IX UT WOS:000383145100015 ER PT J AU Race, B Phillips, K Kraus, A Chesebro, B AF Race, Brent Phillips, Katie Kraus, Allison Chesebro, Bruce TI Phosphorylated human tau associates with mouse prion protein amyloid in scrapie-infected mice but does not increase progression of clinical disease SO PRION LA English DT Article DE amyloid; mouse model; P-tau; prion; scrapie; survival; tau ID STRAUSSLER-SCHEINKER DISEASE; CREUTZFELDT-JAKOB-DISEASE; ALZHEIMERS-DISEASE; MURINE TAU; MODELS; HYPERPHOSPHORYLATION; NEURODEGENERATION; AGGREGATION; TAUOPATHIES AB Tauopathies are a family of neurodegenerative diseases in which fibrils of human hyperphosphorylated tau (P-tau) are believed to cause neuropathology. In Alzheimer disease, P-tau associates with A-beta amyloid and contributes to disease pathogenesis. In familial human prion diseases and variant CJD, P-tau often co-associates with prion protein amyloid, and might also accelerate disease progression. To test this latter possibility, here we compared progression of amyloid prion disease in vivo after scrapie infection of mice with and without expression of human tau. The mice used expressed both anchorless prion protein (PrP) and membrane-anchored PrP, that generate disease associated amyloid and non-amyloid PrP (PrPSc) after scrapie infection. Human P-tau induced by scrapie infection was only rarely associated with non-amyloid PrPSc, but abundant human P-tau was detected at extracellular, perivascular and axonal deposits associated with amyloid PrPSc. This pathology was quite similar to that seen in familial prion diseases. However, association of human and mouse P-tau with amyloid PrPSc did not diminish survival time following prion infection in these mice. By analogy, human P-tau may not affect prion disease progression in humans. Alternatively, these results might be due to other factors, including rapidity of disease, blocking effects by mouse tau, or low toxicity of human P-tau in this model. C1 [Race, Brent; Phillips, Katie; Kraus, Allison; Chesebro, Bruce] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Race, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. EM raceb@niaid.nih.gov NR 27 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 PY 2016 VL 10 IS 4 BP 319 EP 330 DI 10.1080/19336896.2016.1199313 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DW0VP UT WOS:000383361400007 PM 27463540 ER PT J AU Tsuchiya, M Kalurupalle, S Kumar, P Ghoshal, S Zhang, YQ Lehrmann, E Becker, KG Gorospe, M Biswas, R AF Tsuchiya, Motohiro Kalurupalle, Swathi Kumar, Parameet Ghoshal, Sarani Zhang, Yongqing Lehrmann, Elin Becker, Kevin G. Gorospe, Myriam Biswas, Roopa TI RPTOR, a novel target of miR-155, elicits a fibrotic phenotype of cystic fibrosis lung epithelium by upregulating CTGF SO RNA BIOLOGY LA English DT Article DE CTGF; Cystic fibrosis; inflammation; lung epithelium; microRNA; miR-155; RPTOR; TGF- signaling ID TRANSMEMBRANE CONDUCTANCE REGULATOR; TISSUE GROWTH-FACTOR; MICRORNA TARGETS; EXPRESSION; CELLS; MTOR; INTERLEUKIN-8; INFLAMMATION; PATHWAYS; CHILDREN AB Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the most frequent of which is F508del-CFTR. CF is characterized by excessive secretion of pro-inflammatory mediators into the airway lumen, inducing a highly inflammatory cellular phenotype. This process triggers fibrosis, causing airway destruction and leading to high morbidity and mortality. We previously reported that miR-155 is upregulated in CF lung epithelial cells, but the molecular mechanisms by which miR-155 affects the disease phenotype is not understood. Here we report that RPTOR (regulatory associated protein of mTOR, complex 1) is a novel target of miR-155 in CF lung epithelial cells. The suppression of RPTOR expression and subsequent activation of TGF- signaling resulted in the induction of fibrosis by elevating connective tissue growth factor (CTGF) abundance in CF lung epithelial cells. Thus, we propose that miR-155 might regulate fibrosis of CF lungs through the increased CTGF expression, highlighting its potential value in CF therapy. C1 [Tsuchiya, Motohiro] Uniformed Serv Univ Hlth Sci, Mol & Cell Biol Program, Bethesda, MD 20814 USA. [Tsuchiya, Motohiro; Kalurupalle, Swathi; Kumar, Parameet; Ghoshal, Sarani; Biswas, Roopa] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Zhang, Yongqing; Lehrmann, Elin; Becker, Kevin G.; Gorospe, Myriam] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Biswas, R (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. EM roopa.biswas@usuhs.edu FU Cystic Fibrosis Foundation; USUHS; NIA-IRP, NIH FX This study was supported by Cystic Fibrosis Foundation Research Grant and USUHS Intramural funds to RB. YZ, EL, KGB, and MG were supported by the NIA-IRP, NIH. NR 37 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 1547-6286 EI 1555-8584 J9 RNA BIOL JI RNA Biol. PY 2016 VL 13 IS 9 BP 837 EP 847 DI 10.1080/15476286.2016.1197484 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DW0UK UT WOS:000383358100012 PM 27284727 ER PT J AU Kobayashi, Y Dadonaite, B van Doremalen, N Suzuki, Y Barclay, WS Pybus, OG AF Kobayashi, Yuki Dadonaite, Bernadeta van Doremalen, Neeltje Suzuki, Yoshiyuki Barclay, Wendy S. Pybus, Oliver G. TI Computational and molecular analysis of conserved influenza A virus RNA secondary structures involved in infectious virion production SO RNA BIOLOGY LA English DT Article DE Influenza A virus; M segment; packaging signal; RNA secondary structure; stem loop ID PACKAGING SIGNALS; MESSENGER-RNA; SEGMENTS; NUCLEOPROTEIN; REPLICATION; POLYMERASE; REGIONS; PROTEIN; GENE; PB2 AB As well as encoding viral proteins, genomes of RNA viruses harbor secondary and tertiary RNA structures that have been associated with functions essential for successful replication and propagation. Here, we identified stem-loop structures that are extremely conserved among 1,884M segment sequences of influenza A virus (IAV) strains from various subtypes and host species using computational and evolutionary methods. These structures were predicted within the 3 and 5 ends of the coding regions of M1 and M2, respectively, where packaging signals have been previously proposed to exist. These signals are thought to be required for the incorporation of a single copy of 8 different negative-strand RNA segments (vRNAs) into an IAV particle. To directly test the functionality of conserved stem-loop structures, we undertook reverse genetic experiments to introduce synonymous mutations designed to disrupt secondary structures predicted at 3 locations and found them to attenuate infectivity of recombinant virus. In one mutant, predicted to disrupt stem loop structure at nucleotide positions 219-240, attenuation was more evident at increased temperature and was accompanied by an increase in the production of defective virus particles. Our results suggest that the conserved secondary structures predicted in the M segment are involved in the production of infectious viral particles during IAV replication. C1 [Kobayashi, Yuki] Nihon Univ, Vet Res Ctr, Fujisawa, Kanagawa, Japan. [Kobayashi, Yuki; Pybus, Oliver G.] Univ Oxford, Dept Zool, Oxford, England. [Dadonaite, Bernadeta; van Doremalen, Neeltje; Barclay, Wendy S.] Imperial Coll London, Virol Sect, Dept Med, London, England. [van Doremalen, Neeltje] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA. [Suzuki, Yoshiyuki] Nagoya City Univ, Grad Sch Nat Sci, Nagoya, Aichi, Japan. RP Kobayashi, Y (reprint author), Nihon Univ, Vet Res Ctr, Fujisawa, Kanagawa, Japan. EM suzuki.yukikb@nihon-u.ac.jp FU Japan Society for the Promotion of Science [24-448]; European Research Council under the European Commission [614725-PATHPHYLODYN] FX This work was supported by a Japan Society for the Promotion of Science grant to YK (24-448). OGP was supported by the European Research Council under the European Commission Seventh Framework Program (FP7/2007-2013)/European Research Council grant agreement 614725-PATHPHYLODYN. NR 54 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1547-6286 EI 1555-8584 J9 RNA BIOL JI RNA Biol. PY 2016 VL 13 IS 9 BP 883 EP 894 DI 10.1080/15476286.2016.1208331 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DW0UK UT WOS:000383358100016 PM 27399914 ER PT S AU Sosne, G Rimmer, D Kleinman, HK Ousler, G AF Sosne, G. Rimmer, D. Kleinman, H. K. Ousler, G. BE Litwack, G TI Thymosin Beta 4: A Potential Novel Therapy for Neurotrophic Keratopathy, Dry Eye, and Ocular Surface Diseases SO THYMOSINS SE Vitamins and Hormones LA English DT Review; Book Chapter ID CORNEAL EPITHELIAL-CELLS; NF-KAPPA-B; NERVE GROWTH-FACTOR; AMNIOTIC MEMBRANE TRANSPLANTATION; SOFT CONTACT-LENSES; CORD SERUM THERAPY; LIPID RAFTS; INFLAMMATORY MEDIATORS; CLINICAL-APPLICATIONS; ENDOTHELIAL-CELLS AB Chronic ocular surface diseases such as dry eye, blepharitis, and neurotrophic keratopathies represent a significant and a growing therapeutic challenge. The basis of this expanding prevalence is multifactorial and may due to issues such as an aging population, an increasing use of video display terminals, and increases in frequency of refractive surgeries. The growing incidence of diseases such as diabetes may also be a contributing factor. Current treatments for ocular surface disease include artificial tears, lubricants, tear duct plugs, steroids, antibiotics, cyclosporine, scleral lenses, and serum tears. Treatment choices depend on the type and severity of the disease, but in general positive outcomes are limited because many of these treatments do not fully address the underlying disease process or promote mechanisms that facilitate long-term wound repair. From minor corneal injuries to more severe inflammatory-mediated pathologies, clinicians need agents that promote corneal healing and reduce the inflammatory response to prevent visual disturbances and improve quality of life. A focus on treatments that reduce the inflammatory responses while accelerating corneal epithelial growth would represent a major step forward from current treatment options. Increasing evidence suggests that thymosin beta 4 (T beta 4), a naturally occurring polypeptide, can elicit this spectrum of therapeutic responses: a rapid corneal reepithelialization and a reduction in corneal inflammation. This chapter serves as a review of standard therapies as well as recent advancements in the development of newer therapies that includes the use of T beta 4 that is proving to be an exciting new agent for the management of ocular surface disease. C1 [Sosne, G.; Rimmer, D.; Ousler, G.] Wayne State Univ, Sch Med, Kresge Eye Inst, Detroit, MI 48201 USA. [Rimmer, D.; Ousler, G.] ORA Inc, Andover, MA USA. [Kleinman, H. K.] George Washington Univ, Washington, DC USA. [Kleinman, H. K.] NIDCR, NIH, Bethesda, MD USA. RP Sosne, G (reprint author), Wayne State Univ, Sch Med, Kresge Eye Inst, Detroit, MI 48201 USA. EM gsosne@med.wayne.edu NR 121 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0083-6729 BN 978-0-12-805234-1; 978-0-12-804818-4 J9 VITAM HORM JI Vitam. Horm. PY 2016 VL 102 BP 277 EP 306 DI 10.1016/bs.vh.2016.04.012 PG 30 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BF6OA UT WOS:000383369100013 PM 27450739 ER PT J AU Rocco, MV Chapman, A Chertow, GM Cohen, D Chen, J Cutler, JA Diamond, MJ Freedman, BI Hawfield, A Judd, E Killeen, AA Kirchner, K Lewis, CE Pajewski, NM Wall, BM Yee, J AF Rocco, Michael V. Chapman, Arlene Chertow, Glenn M. Cohen, Debbie Chen, Jing Cutler, Jeffrey A. Diamond, Matthew J. Freedman, Barry I. Hawfield, Amret Judd, Eric Killeen, Anthony A. Kirchner, Kent Lewis, Cora E. Pajewski, Nicholas M. Wall, Barry M. Yee, Jerry CA SPRINT Res Grp TI Chronic Kidney Disease Classification in Systolic Blood Pressure Intervention Trial: Comparison Using Modification of Diet in Renal Disease and CKD-Epidemiology Collaboration Definitions SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Chronic kidney disease; Modification of Diet in Renal; Disease study equation; CKD-Epidemiology Collaboration equation; Hypertension; Elderly; Cardiovascular disease; Clinical trial ID GLOMERULAR-FILTRATION-RATE; EPI EQUATIONS; MDRD; RISK; GFR; MORTALITY AB Background: Interventional trials have used either the Modification of Diet in Renal Disease (MDRD) or chronic kidney disease (CKD)-Epidemiology Collaboration (CKD-EPI) equation for determination of estimated glomerular filtration rate (eGFR) to define whether participants have stages 3-5 CKD. The equation used to calculate eGFR may influence the number and characteristics of participants designated as having CKD. Methods: We examined the classification of CKD at baseline using both equations in the Systolic Blood Pressure Intervention Trial (SPRINT). eGFR was calculated at baseline using fasting serum creatinine values from a central laboratory. Results: Among 9,308 participants with baseline CKD classification using the 4-variable MDRD equation specified in the SPRINT protocol, 681 (7.3%) participants were reclassified to a less advanced CKD stage (higher eGFR) and 346 (3.7%) were reclassified to a more advanced CKD stage (lower eGFR) when the CKD-EPI equation was used to calculate eGFR. For eGFRs <90 ml/min/1.73 m(2), participants <75 years were more likely to be reclassified to a less advanced CKD stage; this reclassification was more likely to occur in non blacks rather than blacks. Participants aged >= 75 years were more likely to be reclassified to a more advanced than a less advanced CKD stage, regardless of baseline CKD stage. Reclassification of baseline CKD status (eGFR <60 ml/min/1.73 m(2)) occurred in 3% of participants. Conclusions: Use of the MDRD equation led to a higher percentage of participants being classified as having CKD stages 3-4. Younger and non-black participants were more likely to be reclassified as not having CKD using the CKD-EPI equation. (C) 2016 S. Karger AG, Basel C1 [Rocco, Michael V.; Freedman, Barry I.; Hawfield, Amret; Pajewski, Nicholas M.] Wake Forest Sch Med, Winston Salem, NC USA. [Chapman, Arlene] Univ Chicago, Chicago, IL 60637 USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Cohen, Debbie] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Chen, Jing] Tulane Univ, Sch Med, 1430 Tulane Ave, New Orleans, LA 70112 USA. [Cutler, Jeffrey A.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Diamond, Matthew J.] Med Coll Georgia, Augusta, GA 30912 USA. [Judd, Eric; Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA. [Kirchner, Kent] Vet Affairs Med Ctr, Jackson, MS USA. [Kirchner, Kent] Univ Mississippi, Sch Med, Jackson, MS USA. [Killeen, Anthony A.] Univ Minnesota, Minneapolis, MN USA. [Wall, Barry M.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Wall, Barry M.] Vet Affairs Med Ctr, Memphis, TN USA. [Yee, Jerry] Henry Ford Hlth Syst, Detroit, MI USA. RP Rocco, MV (reprint author), Wake Forest Sch Med, Nephrol Sect, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM mrocco@wakehealth.edu FU Novo Nordisk FX A.C. was a consultant for Kadmon, Otsuka. C.E.L. had research funding (paid to the institution) from Novo Nordisk. All other authors have no relevant disclosures. NR 17 TC 0 Z9 0 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2016 VL 44 IS 2 BP 130 EP 140 DI 10.1159/000448722 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA DV8WA UT WOS:000383216200006 PM 27513312 ER PT J AU Heale, BSE Overby, CL Del Fiol, G Rubinstein, WS Maglott, DR Nelson, TH Milosavljevic, A Martin, CL Goehringer, SR Freimuth, RR Williams, MS AF Heale, Bret S. E. Overby, Casey Lynnette Del Fiol, Guilherme Rubinstein, Wendy S. Maglott, Donna R. Nelson, Tristan H. Milosavljevic, Aleksandar Martin, Christa L. Goehringer, Scott R. Freimuth, Robert R. Williams, Marc S. TI Integrating Genomic Resources with Electronic Health Records using the HL7 Infobutton Standard SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Clinical information systems; standards adoption; HL7; genetics; clinical decision support ID INFORMATION-RETRIEVAL; KNOWLEDGE RESOURCES; CLINICAL GENOME; MIXED METHODS; PHYSICIANS; HOSPITALS; SYSTEMS; IMPACT; CARE AB Background: The Clinical Genome Resource (ClinGen) Electronic Health Record (EHR) Workgroup aims to integrate ClinGen resources with EHRs. A promising option to enable this integration is through the Health Level Seven (HL7) Infobutton Standard. EHR systems that are certified according to the US Meaningful Use program provide HL7-compliant infobutton capabilities, which can be leveraged to support clinical decision-making in genomics. Objectives: To integrate genomic knowledge resources using the HL7 infobutton standard. Two tactics to achieve this objective were: (1) creating an HL7-compliant search interface for ClinGen, and (2) proposing guidance for genomic resources on achieving HL7 Infobutton standard accessibility and compliance. Methods: We built a search interface utilizing OpenInfobutton, an open source reference implementation of the HL7 Infobutton standard. ClinGen resources were assessed for readiness towards HL7 compliance. Finally, based upon our experiences we provide recommendations for publishers seeking to achieve HL7 compliance. Results: Eight genomic resources and two sub-resources were integrated with the ClinGen search engine via OpenInfobutton and the HL7 infobutton standard. Resources we assessed have varying levels of readiness towards HL7-compliance. Furthermore, we found that adoption of standard terminologies used by EHR systems is the main gap to achieve compliance. Conclusion: Genomic resources can be integrated with EHR systems via the HL7 Infobutton standard using OpenInfobutton. Full compliance of genomic resources with the Infobutton standard would further enhance interoperability with EHR systems. C1 [Heale, Bret S. E.; Del Fiol, Guilherme] Univ Utah, Salt Lake City, UT USA. [Overby, Casey Lynnette] Johns Hopkins Univ, Baltimore, MD USA. [Rubinstein, Wendy S.; Maglott, Donna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. [Overby, Casey Lynnette; Nelson, Tristan H.; Martin, Christa L.; Goehringer, Scott R.; Williams, Marc S.] Geisinger Hlth Syst, Danville, PA USA. [Milosavljevic, Aleksandar] Baylor Coll Med, Houston, TX 77030 USA. [Freimuth, Robert R.] Mayo Clin, Rochester, MN USA. [Heale, Bret S. E.] Intermt Healthcare, Salt Lake City, UT USA. RP Heale, BSE (reprint author), 421 Wakara Way 140, Salt Lake City, UT 84108 USA. EM bheale@gmail.com OI Overby, Casey/0000-0001-9302-5968 FU NLM Postdoctoral Training Grant [T15LM007124]; National Human Genome Research Institute FX Bret Heale was supported by a NLM Postdoctoral Training Grant (T15LM007124). ClinGen is funded by the National Human Genome Research Institute NR 28 TC 0 Z9 0 U1 2 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2016 VL 7 IS 3 BP 817 EP 831 DI 10.4338/ACI-2016-04-RA-0058 PG 15 WC Medical Informatics SC Medical Informatics GA DU5XP UT WOS:000382287300016 PM 27579472 ER PT J AU Wasserman, D Aas, S AF Wasserman, David Aas, Sean TI BCIs and disability: enhancement, environmental modification, and embodiment SO BRAIN-COMPUTER INTERFACES LA English DT Article DE [BCIs]; disabilities; inclusion; functioning; assistive devices; universal design; prosthetics; embodiment; dual valence AB This paper explores the ways that BCIs can modify the environment as well as the individual, blur the boundaries between them, and thereby affect the physical functioning and social inclusion of people with disabilities. We begin by outlining the traditional distinction between two kinds of technology that serve people with disabilities: assistive devices and universal design. We then examine a spectrum of BCI applications, from prosthetic attachments to public infrastructure, with the potential to vastly improve the functioning of both disabled and nondisabled people, and to diminish the importance and salience of physical impairments. We suggest that these applications will erode the distinction between assistive devices and universal design as they blur the lines between individual and environmental modifications. Our optimism is tempered by concern for the impact that BCI technology may have on our embodied connection to the physical world and on people with intellectual disabilities. We find the latter concern more disturbing than the former, but speculate that both may be mitigated by the same technology that raises them. We conclude by suggesting that the complexities in appraising the impact of BCI technology on people with disabilities reflect their "dual valence": the fact that the same uses of that technology have good and bad aspects. C1 [Wasserman, David; Aas, Sean] NIH, Dept Bioeth, Room 1C118, Bethesda, MD 20892 USA. RP Aas, S (reprint author), NIH, Dept Bioeth, Room 1C118, Bethesda, MD 20892 USA. EM sean.aas@gmail.com NR 18 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 2326-263X EI 2326-2621 J9 BRAIN-COMPUT INTERFA JI Brain Comput. Interfaces PY 2016 VL 3 IS 3 BP 126 EP 132 DI 10.1080/2326263X.2016.1207127 PG 7 WC Neurosciences SC Neurosciences & Neurology GA DV3VX UT WOS:000382853700002 ER PT J AU Jin, X Sviridov, D Liu, Y Vaisman, B Addadi, L Remaley, AT Kruth, HS AF Jin, X. Sviridov, D. Liu, Y. Vaisman, B. Addadi, L. Remaley, A. T. Kruth, H. S. TI MACROPHAGE DEPOSITION OF CHOLESTEROL INTO THE EXTRACELLULAR MATRIX - A PATHWAY FOR REVERSE CHOLESTEROL TRANSPORT SO CARDIOLOGY LA English DT Meeting Abstract C1 [Jin, X.; Liu, Y.; Kruth, H. S.] NHLBI, Expt Atherosclerosis Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. [Sviridov, D.; Vaisman, B.; Remaley, A. T.] NHLBI, Lipoprotein Metab Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. [Addadi, L.] Weizmann Inst Sci, Dept Biol Struct, Rehovot, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 SU 1 MA 075 BP 87 EP 87 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DV6NH UT WOS:000383053200075 ER PT J AU Kulina, RA Wiley, B Agarwal, S Traube, A Ka, S Schiller, S Clark, L Narula, J Sengupta, P Chaudhry, F AF Kulina, R. A. Wiley, B. Agarwal, S. Traube, A. Ka, S. Schiller, S. Clark, L. Narula, J. Sengupta, P. Chaudhry, F. TI NEW SOFTWARE BASED BEAMFORMING ALGORITHM IS SUPERIOR TO HARDWARE BASED BEAMFORMER IN ENDOCARDIAL BORDER DETECTION SO CARDIOLOGY LA English DT Meeting Abstract C1 [Kulina, R. A.; Agarwal, S.; Traube, A.; Ka, S.; Schiller, S.; Clark, L.; Narula, J.; Sengupta, P.; Chaudhry, F.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Wiley, B.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 SU 1 MA 182 BP 194 EP 194 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DV6NH UT WOS:000383053200182 ER PT J AU Ko, D Riles, EM Marcos, EG Magnani, JW Lubitz, SA Lin, H Long, MT Schnabel, RB McManus, DD Ellinor, PT Ramachandran, VS Wang, TJ Gerszten, RE Benjamin, EJ Yin, X Rienstra, M AF Ko, D. Riles, E. M. Marcos, E. G. Magnani, J. W. Lubitz, S. A. Lin, H. Long, M. T. Schnabel, R. B. McManus, D. D. Ellinor, P. T. Ramachandran, V. S. Wang, T. J. Gerszten, R. E. Benjamin, E. J. Yin, X. Rienstra, M. TI METABOLOMIC PROFILING IN RELATION TO NEW-ONSET ATRIAL FIBRILLATION IN THE COMMUNITY: THE FRAMINGHAM HEART STUDY SO CARDIOLOGY LA English DT Meeting Abstract C1 [Ko, D.] Boston Univ, Sch Med, Boston Med Ctr, Dept Internal Med,Sect Gen Internal Med, Boston, MA 02118 USA. [Riles, E. M.; Magnani, J. W.; Ramachandran, V. S.; Benjamin, E. J.] Boston Univ, Sch Med, Boston Med Ctr, Dept Internal Med,Sect Cardiovasc Med, Boston, MA 02118 USA. [Ramachandran, V. S.; Benjamin, E. J.] Boston Univ, Sch Med, Boston Med Ctr, Sect Prevent Med,Dept Internal Med, Boston, MA 02118 USA. [Long, M. T.] Boston Univ, Sch Med, Boston Med Ctr, Sect Gastroenterol,Dept Internal Med, Boston, MA 02118 USA. [Ko, D.; Ramachandran, V. S.; Benjamin, E. J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Ko, D.] Boston Univ, Sch Med, Clin & Translat Sci Inst, Boston, MA 02118 USA. [Marcos, E. G.; Rienstra, M.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 AB Groningen, Netherlands. [Lubitz, S. A.; Ellinor, P. T.; Gerszten, R. E.] Harvard Med Sch, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. [Lubitz, S. A.; Ellinor, P. T.] Harvard Med Sch, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA USA. [Lin, H.; Ramachandran, V. S.; Benjamin, E. J.; Yin, X.] Boston Univ, Framingham, MA USA. [Lin, H.; Ramachandran, V. S.; Benjamin, E. J.; Yin, X.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Schnabel, R. B.] Univ Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, Hamburg, Germany. [McManus, D. D.] Univ Massachusetts, Sch Med, Div Cardiovasc Med, Worcester, MA USA. [Wang, T. J.] Vanderbilt Univ, Div Cardiovasc Med, 221 Kirkland Hall, Nashville, TN 37235 USA. [Yin, X.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Ramachandran, V. S.; Benjamin, E. J.] Boston Univ, Sch Publ Hlth, Epidemiol, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 SU 1 MA 212 BP 225 EP 225 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DV6NH UT WOS:000383053200213 ER PT J AU Galis, ZS AF Galis, Z. S. TI HYPERTENSION UPDATE: QUO VADIMUS? SO CARDIOLOGY LA English DT Meeting Abstract C1 [Galis, Z. S.] NHLBI, Vasc Biol & Hypertens, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 SU 1 MA 306 BP 319 EP 319 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DV6NH UT WOS:000383053200306 ER PT J AU Bharti, SK Brosh, RM AF Bharti, Sanjay Kumar Brosh, Robert M., Jr. TI Fine-tuning DNA repair by protein acetylation SO CELL CYCLE LA English DT Editorial Material DE Acetylation; base excision repair; cancer; DNA repair; disease; mismatch repair; mutation; post-translational modification ID POSTTRANSLATIONAL MODIFICATIONS; LYSINE C1 [Bharti, Sanjay Kumar; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM broshr@mail.nih.gov NR 6 TC 0 Z9 0 U1 2 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2016 VL 15 IS 15 BP 1952 EP 1953 DI 10.1080/15384101.2016.1191250 PG 2 WC Cell Biology SC Cell Biology GA DU5DR UT WOS:000382232900007 PM 27292584 ER PT B AU Khaleque, A Rahman, MMZ Anwar, KS Uddin, MN AF Khaleque, Abdul Rahman, Mohammad Mustafi Zur Anwar, Kazi Selim Uddin, Md. Nazim BE Bari, ML Ukuku, DO TI Impact of Changing Lifestyles and Consumer Demands on Food Safety SO FOODBORNE PATHOGENS AND FOOD SAFETY SE Food Biology Series LA English DT Article; Book Chapter ID MIDDLE-INCOME COUNTRIES; GREAT-BRITAIN; CONVENIENCE ORIENTATION; COLLEGE-STUDENTS; DECISION-MAKING; INSTRUMENT FRL; CHOICE MOTIVES; DIET QUALITY; TRUST; KNOWLEDGE C1 [Khaleque, Abdul] North South Univ, Dept Biol & Chem, Dhaka 1229, Bangladesh. [Rahman, Mohammad Mustafi Zur] NIDDK, NIH, Bethesda, MD 20892 USA. [Anwar, Kazi Selim] AIMST Univ, Fac Med, Dept Microbiol, Bedong 08100, Kedah, Malaysia. [Uddin, Md. Nazim] Bangladesh Agr Res Inst, Gazipur 1701, Bangladesh. RP Khaleque, A (reprint author), North South Univ, Dept Biol & Chem, Dhaka 1229, Bangladesh. EM akhaleque@northsouth.edu NR 93 TC 0 Z9 0 U1 2 U2 2 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4987-2410-4; 978-1-4987-2408-1 J9 FOOD BIOL SER PY 2016 BP 213 EP 236 PG 24 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BF6EB UT WOS:000382997500013 ER PT J AU Levy, KY Barracchini, KC Adams, SD Flegel, WA AF Levy, Kimberly Y. Barracchini, Kathleen C. Adams, Sharon D. Flegel, Willy A. TI EVALUATION OF LABTYPE CWD AND XR ASSAYS UTILIZING LABSCAN3D FOR HIGH THROUGHPUT/RESOLUTION HLA TYPING SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY SEP 26-30, 2016 CL St Louis, MO SP Amer Soc Histocompatibil & Immunogenet C1 [Levy, Kimberly Y.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Barracchini, Kathleen C.; Adams, Sharon D.; Flegel, Willy A.] NIH, Dept Transfus Med, 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 0198-8859 EI 1879-1166 J9 HUM IMMUNOL JI Hum. Immunol. PY 2016 VL 77 SU 1 MA P018 BP 54 EP 54 PG 1 WC Immunology SC Immunology GA DW0EK UT WOS:000383313500072 ER PT J AU Chouraki, V Reitz, C Maury, F Bis, JC Bellenguez, C Yu, L Jakobsdottir, J Mukherjee, S Adams, HH Choi, SH Larson, EB Fitzpatrick, A Uitterlinden, AG de Jager, PL Hofman, A Gudnason, V Vardarajan, B Ibrahim-Verbaas, C van der Lee, SJ Lopez, O Dartigues, JF Berr, C Amouyel, P Bennett, DA van Duijn, C DeStefano, AL Launer, LJ Ikram, MA Crane, PK Lambert, JC Mayeux, R Seshadri, S AF Chouraki, Vincent Reitz, Christiane Maury, Fleur Bis, Joshua C. Bellenguez, Celine Yu, Lei Jakobsdottir, Johanna Mukherjee, Shubhabrata Adams, Hieab H. Choi, Seung Hoan Larson, Eric B. Fitzpatrick, Annette Uitterlinden, Andre G. de Jager, Philip L. Hofman, Albert Gudnason, Vilmundur Vardarajan, Badri Ibrahim-Verbaas, Carla van der Lee, Sven J. Lopez, Oscar Dartigues, Jean-Francois Berr, Claudine Amouyel, Philippe Bennett, David A. van Duijn, Cornelia DeStefano, Anita L. Launer, Lenore J. Ikram, M. Arfan Crane, Paul K. Lambert, Jean-Charles Mayeux, Richard Seshadri, Sudha CA Int Genomics Alzheimer's Project TI Evaluation of a Genetic Risk Score to Improve Risk Prediction for Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; clinical utility; cohort studies; genetic risk score; IGAP; meta-analysis; risk prediction ID GENOME-WIDE ASSOCIATION; MILD COGNITIVE IMPAIRMENT; IDENTIFIES VARIANTS; COMMON VARIANTS; LOCI; ONSET; DEMENTIA; TRIALS; CD33; INDIVIDUALS AB Effective prevention of Alzheimer's disease (AD) requires the development of risk prediction tools permitting preclinical intervention. We constructed a genetic risk score (GRS) comprising common genetic variants associated with AD, evaluated its association with incident AD and assessed its capacity to improve risk prediction over traditional models based on age, sex, education, and APOE epsilon 4. In eight prospective cohorts included in the International Genomics of Alzheimer's Project (IGAP), we derived weighted sum of risk alleles from the 19 top SNPs reported by the IGAPGWAS in participants aged 65 and older without prevalent dementia. Hazard ratios (HR) of incident AD were estimated in Cox models. Improvement in risk prediction was measured by the difference in C-index (Delta-C), the integrated discrimination improvement (IDI) and continuous net reclassification improvement (NRI>0). Overall, 19,687 participants at risk were included, of whom 2,782 developed AD. The GRS was associated with a 17% increase in AD risk (pooled HR=1.17; 95% CI = [1.13-1.21] per standard deviation increase in GRS; p-value = 2.86x10(-16)). This association was stronger among persons with at least one APOE epsilon 4 allele (HRGRS = 1.24; 95% CI = [1.15-1.34]) than in others (HRGRS = 1.13; 95% CI = [1.08-1.18]; p(interaction) = 3.45x10(-2)). Risk prediction after seven years of follow-up showed a small improvement when adding the GRS to age, sex, APOE epsilon 4, and education (Delta-Cindex = 0.0043 [0.0019-0.0067]). Similar patterns were observed for IDI and NRI>0. In conclusion, a risk score incorporating common genetic variation outside the APOE epsilon 4 locus improved AD risk prediction and may facilitate risk stratification for prevention trials. C1 [Chouraki, Vincent; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Chouraki, Vincent; Seshadri, Sudha] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Reitz, Christiane; Vardarajan, Badri; Mayeux, Richard] Columbia Univ, New York, NY USA. [Maury, Fleur; Bellenguez, Celine; Amouyel, Philippe; Lambert, Jean-Charles] Univ Lille, Lille Univ Hosp, INSERM, Inst Pasteur Lille,U1167 RID AGE Risk Factors & M, Lille, France. [Maury, Fleur; Bellenguez, Celine; Amouyel, Philippe; Lambert, Jean-Charles] Labex Distalz, Lille, France. [Bis, Joshua C.; Mukherjee, Shubhabrata; Larson, Eric B.; Fitzpatrick, Annette; Crane, Paul K.] Univ Washington, Seattle, WA USA. [Yu, Lei; Bennett, David A.] Rush Alzheimers Dis Ctr, Chicago, IL USA. [Jakobsdottir, Johanna; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Adams, Hieab H.; Uitterlinden, Andre G.; Hofman, Albert; Ibrahim-Verbaas, Carla; van der Lee, Sven J.; van Duijn, Cornelia; Ikram, M. Arfan] Erasmus MC, Rotterdam, Netherlands. [DeStefano, Anita L.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Larson, Eric B.; Crane, Paul K.] Grp Hlth Res Inst, Seattle, WA USA. [de Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA. [de Jager, Philip L.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Lopez, Oscar] Univ Pittsburgh, Sch Med, Alzheimers Dis Res Ctr, Dept Neurol,Dept Psychiat, Pittsburgh, PA 15261 USA. [Lopez, Oscar] Univ Pittsburgh, Sch Med, Dept Psychol, Pittsburgh, PA 15261 USA. [Dartigues, Jean-Francois] Univ Bordeaux, Bordeaux Populat Hlth, Inserm U1219, Bordeaux, France. [Berr, Claudine] Univ Montpellier, Inserm Neuropsychiat Epidemiol & Clin Res U1061, Montpellier, France. [Launer, Lenore J.] NIA, Bethesda, MD 20892 USA. RP Chouraki, V (reprint author), Boston Univ, Sch Med, Dept Neurol, Framingham Study, 72 East Concord St B-601, Boston, MA 02118 USA. EM vchourak@bu.edu OI Lambert, Jean-Charles/0000-0003-0829-7817 FU National Foundation for Alzheimer's disease and related disorders; Institut Pasteur de Lille; Centre National de Genotypage; Inserm; FRC (fondation pour la recherche sur le cerveau); Rotary; LABEX (laboratory of excellence program investment for the future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease); eMERGE genotyping [1U01HG006375, U01HG004610]; NEI; NIDCD; NIA Intramural Research Program; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); NHLBI [HHSN2682012000 36C, HHSN268200800007C, N01HC55222, N01 HC85079, N01HC85080, N01HC85081, N01HC 85082, N01HC85083, N01HC85086, U01HL080295, R01HL087652, R01HL1 05756, R01HL103612, R01HL120393, N01HC25105, HHSN268201500001I]; National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA) [R01AG023629, R01AG15928, R01AG20098, R01AG027058]; National Center for Advancing Translational Sciences, CTSI grant [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant [DK063491]; NIA [R01AG008122, R01AG033193, U01AG 049505, N01-AG-12100]; National Institute on Aging [P30AG10161, R01AG17917, R01AG15819, R01AG30146]; Illinois Department of Public Health; Translational Genomics Research Institute; Erasmus MC University Medical Center; Erasmus University Rotterdam; Netherlands Organisation for Scientific Research (NWO); Netherlands Organisation for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Netherlands Genomics Initiative (NGI); Ministry of Education, Culture and Science; Ministry of Health, Welfare and Sports; Municipality of Rotterdam; National Institutes of Health [AG037212]; European Commission (DG XII); [U01AG006781] FX The Three City study was supported by the National Foundation for Alzheimer's disease and related disorders, the Institut Pasteur de Lille, the Centre National de Genotypage, Inserm, FRC (fondation pour la recherche sur le cerveau), Rotary and the LABEX (laboratory of excellence program investment for the future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease).; The Adult Changes in Thought study was supported by the following grants: U01AG006781 (Larson, PI); eMERGE genotyping 1U01HG006375 and U01HG004610 (Larson and Jarvik, multiple Pis).; The Aging Gene-Environment Susceptibility-Reykjavik Study has been funded by NIA Contract N01-AG-12100 with contributions from NEI, NIDCD and NHLBI, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament).; This Cardiovascular Health Study research was supported by NHLBI contracts HHSN2682012000 36C, HHSN268200800007C, N01HC55222, N01 HC85079, N01HC85080, N01HC85081, N01HC 85082, N01HC85083, N01HC85086; and NHLBI grants U01HL080295, R01HL087652, R01HL1 05756, R01HL103612, and R01HL120393 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629, R01AG15928, R01AG20098, and R01AG027058 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; The Framingham Heart Study was supported by contracts with the NHLBI (N01HC25105, and HHSN268201500001I) and grants from the NIA (R01AG008122, R01AG033193, and U01AG 049505).; The MAP and ROS data in the analysis is supported by National Institute on Aging grants P30AG10161, R01AG17917, R01AG15819, R01AG30146, the Illinois Department of Public Health, and the Translational Genomics Research Institute.; The Rotterdam Study is supported by the Erasmus MC University Medical Center and Erasmus University Rotterdam; The Netherlands Organisation for Scientific Research (NWO); The Netherlands Organisation for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); The Netherlands Genomics Initiative (NGI); the Ministry of Education, Culture and Science; the Ministry of Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam.; The Washington Heights-Inwood Community Aging Project was supported in part by grants from National Institutes of Health (AG037212). NR 34 TC 3 Z9 3 U1 4 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2016 VL 53 IS 3 BP 921 EP 932 DI 10.3233/JAD-150749 PG 12 WC Neurosciences SC Neurosciences & Neurology GA DV7WE UT WOS:000383148100012 PM 27340842 ER PT J AU Armstrong, JJ Godin, J Launer, LJ White, LR Mitnitski, A Rockwood, K Andrew, MK AF Armstrong, Joshua J. Godin, Judith Launer, Lenore J. White, Lon R. Mitnitski, Arnold Rockwood, Kenneth Andrew, Melissa K. TI Changes in Frailty Predict Changes in Cognition in Older Men: The Honolulu-Asia Aging Study SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Aging; cognition; cohort studies; frail elderly; risk factors ID APOLIPOPROTEIN-E EPSILON-4; JAPANESE-AMERICAN MEN; ADULT LIFE-SPAN; DEFICIT ACCUMULATION; ALZHEIMER-DISEASE; RELATIVE FITNESS; BRAIN PATHOLOGY; CLINICAL-TRIALS; ELDERLY-PEOPLE; BIOLOGICAL AGE AB Background: As cognitive decline mostly occurs in late life, where typically it co-exists with many other ailments, it is important to consider frailty in understanding cognitive change. Objective: Here, we examined the association of change in frailty status with cognitive trajectories in a well-studied cohort of older Japanese-American men. Methods: Using the prospective Honolulu-Asia Aging Study (HAAS), 2,817 men of Japanese descent were followed (aged 71-93 at baseline). Starting in 1991 with follow-up health assessments every two to three years, cognition was measured using the Cognitive Abilities Screening Instrument (CASI). For this study, health data was used to construct an accumulation of deficits frailty index (FI). Using six waves of data, multilevel growth curve analyses were constructed to examine simultaneous changes in cognition in relation to changes in FI, controlling for baseline frailty, age, education, and APOE-epsilon 4 status. Results: On average, CASI scores declined by 2.0 points per year (95% confidence interval 1.9-2.1). Across six waves, each 10% within-person increase in frailty from baseline was associated with a 5.0 point reduction in CASI scores (95% confidence interval 4.7-5.2). Baseline frailty and age were associated both with lower initial CASI scores and with greater decline across the five follow-up assessments (p < 0.01). Discussion: Cognition is adversely affected by impaired health status in old age. Using a multidimensional measure of frailty, both baseline status and within-person changes in frailty were predictive of cognitive trajectories. C1 [Armstrong, Joshua J.; Mitnitski, Arnold; Rockwood, Kenneth; Andrew, Melissa K.] Dalhousie Univ, Dept Med, Geriatr Med Res Unit, Halifax, NS, Canada. [Godin, Judith; Andrew, Melissa K.] Nova Scotia Hlth Author, Geriatr Med Res Unit, Halifax, NS, Canada. [Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [White, Lon R.] Pacific Hlth Res & Educ Inst, Honolulu, HI USA. RP Rockwood, K (reprint author), Suite 1421 Vet Mem Bldg,5955 Vet Mem Lane, Halifax, NS B3H 2E1, Canada. EM Kenneth.Rockwood@dal.ca FU Canadian Consortium on Neurodegeneration in Aging - Canadian Institute of Health Research [CNA-137794]; Intramural Research Program, National Institute on Aging FX This work was supported by the Canadian Consortium on Neurodegeneration in Aging, which receives funding from the Canadian Institute of Health Research (CNA-137794) and partner organizations (http://www.ccna-ccnv.ca). This study is part of a Canadian Consortium on Neurodegeneration in Aging investigation into how multi-morbidity modifies the risk of dementia and the patterns of disease expression (Team 14). Data reported in this article were collected as part of the Honolulu-Asia Aging Study, which was partially supported by the Intramural Research Program, National Institute on Aging. NR 67 TC 1 Z9 1 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2016 VL 53 IS 3 BP 1003 EP 1013 DI 10.3233/JAD-151172 PG 11 WC Neurosciences SC Neurosciences & Neurology GA DV7WE UT WOS:000383148100019 PM 27314525 ER PT J AU Callisaya, ML Ayers, E Barzilai, N Ferrucci, L Guralnik, JM Lipton, RB Otahal, P Srikanth, VK Verghese, J AF Callisaya, Michele L. Ayers, Emmeline Barzilai, Nir Ferrucci, Luigi Guralnik, Jack M. Lipton, Richard B. Otahal, Petr Srikanth, Velandai K. Verghese, Joe TI Motoric Cognitive Risk Syndrome and Falls Risk: A Multi-Center Study SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Cognition; dementia; falls; gait ID SUBJECTIVE MEMORY COMPLAINTS; HEALTHY OLDER-ADULTS; GAIT VARIABILITY; PEOPLE; POPULATION; METAANALYSIS; PERFORMANCE; IMPAIRMENT; PREDICTOR; DEMENTIA AB Background: The Motoric Cognitive Risk Syndrome (MCR) is characterized by slow gait speed and cognitive complaints. Objectives: The objective of this study was to determine if the presence of MCR increases the risk of falls in older people. Methods: Individual participant data (n = 6,204) from five longitudinal studies from three countries were used for this analysis. MCR diagnosis was defined as both the presence of objectively measured slow gait speed and subjective cognitive complaints in those without dementia or mobility disability. Falls were prospectively ascertained using phone calls or questionnaires. Log binomial regression was performed to determine if MCR increased the risk of falls separately in each cohort. Random effects meta-analysis was used to pool results from all cohorts. Results: The mean age of participants was 74.9 (SD 6.8) years and 44% (n = 2728) were male. Overall 33.9% (n = 2104) reported a fall over follow-up. Pooled relative risk of MCR with any falls was RR 1.44 95% CI 1.16, 1.79. The components of MCR, slow gait (RR 1.30 95% CI 1.14, 1.47) and cognitive complaint (RR 1.25, 95% CI 1.07, 1.46) were also associated with an increased risk of any falls. In sub-analyses MCR was associated with any fall independent of previous falls (RR 1.29 95% CI 1.09, 1.53) and with multiple falls (RR 1.77, 95% CI 1.25, 2.51). Conclusion: MCR is associated with an increased risk of falls. The increase in risk was higher than for its individual components. The simplicity of the MCR makes it an attractive falls risk screening tool for the clinic. C1 [Callisaya, Michele L.; Otahal, Petr; Srikanth, Velandai K.] Univ Tasmania, Menzies Inst Med Res, Liverpool St, Hobart, Tas, Australia. [Callisaya, Michele L.; Srikanth, Velandai K.] Monash Univ, Sch Clin Sci, Stroke & Ageing Res Grp, Monash Hlth,Dept Med, Clayton, Vic, Australia. [Ayers, Emmeline; Lipton, Richard B.; Verghese, Joe] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. [Barzilai, Nir; Verghese, Joe] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Gerontol Res Ctr, Clin Res Branch, Baltimore, MD 21224 USA. [Guralnik, Jack M.] Univ Maryland, Sch Med, Div Gerontol, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Lipton, Richard B.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Callisaya, ML (reprint author), Univ Tasmania, Menzies Inst Med Res, Liverpool St, Hobart, Tas, Australia. EM michele.callisaya@utas.edu.au RI Callisaya, Michele/I-2333-2013 OI Callisaya, Michele/0000-0003-2122-1622 FU NIH [R00AG037574, 1P01AG034906, R01AG046949, 1R01AG042188, P30AG038072, R37AG18381, 263 MD916413, 263 MD 821336, 1ZIAAG001050]; CTSA [KL2TR000088]; Einstein Glenn; Paul Glenn Foundation; American Federation for Aging Research; National Institute on Aging [1P01AG03949, NIA U01AG009740]; Italian Ministry of Health [ICS 110.1/RS97.71]; National Health and Medical Research Council (NHMRC) [403000, 491109]; NHMRC [APP 1034483, APP1061457]; Heart Foundation Future Leader Fellowship [100089] FX The LonGenity Study was funded by NIH (R00AG037574, 1P01AG034906, R01AG046949, 1R01AG042188, P30AG038072, and NIH R37AG18381), CTSA KL2TR000088, Einstein Glenn, Paul Glenn Foundation, and the American Federation for Aging Research.; The Einstein Aging Study was funded by the National Institute on Aging (1P01AG03949).; The HRS (Health and Retirement Study) is sponsored by the National Institute on Aging (grant number NIA U01AG009740) and is conducted by the University of Michigan.; The InCHIANTI Study was funded by the Italian Ministry of Health (grant ICS 110.1/RS97.71) and NIH (grants 263 MD916413, 263 MD 821336, 1ZIAAG001050).; TASCOG was funded by National Health and Medical Research Council (NHMRC) grants 403000 and 491109.; Dr M Callisaya was supported by an NHMRC Early Career Fellowship (APP 1034483).; Prof VK Srikanth is supported by an NHMRC Career Development Fellowship (APP1061457) and a Heart Foundation Future Leader Fellowship (ID 100089). NR 42 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2016 VL 53 IS 3 BP 1043 EP 1052 DI 10.3233/JAD-160230 PG 10 WC Neurosciences SC Neurosciences & Neurology GA DV7WE UT WOS:000383148100022 PM 27340851 ER PT J AU Liao, HS Lin, J Liu, Y Huang, P Jin, A Chen, XY AF Liao, Hsien-Shun Lin, Jing Liu, Yang Huang, Peng Jin, Albert Chen, Xiaoyuan TI Self-assembly mechanisms of nanofibers from peptide amphiphiles in solution and on substrate surfaces SO NANOSCALE LA English DT Article ID ATOMIC-FORCE MICROSCOPY; AMYLOID FIBRILS; ALPHA-SYNUCLEIN; MOLECULAR-DYNAMICS; CELLULAR MOTILITY; CONTACT-ANGLE; BETA PEPTIDE; NANOSTRUCTURES; DESIGN; MICROTUBULES AB We report the investigation of the self-assembly mechanism of nanofibers, using a small peptide amphiphile (NapFFKYp) as a model. Combining experimental and simulation methods, we identify the self-assembly pathways in the solution and on the substrates, respectively. In the solution, peptide amphiphiles undergo the nucleation process to grow into nanofibers. The nanofibers can further twist into high-ordered nanofibers with aging. On the substrates, peptide amphiphiles form nanofibers and nanosheet structures simultaneously. This surface-induced nanosheet consists of rod-like structures, and its thickness is substrate-dependent. Most intriguingly, water can transform the nanosheet into the nanofiber. Molecular dynamic simulation suggests that hydrophobic and ion-ion interactions are dominant forces during the self-assembly process. C1 [Liao, Hsien-Shun] Natl Taiwan Univ, Dept Mech Engn, Taipei 10617, Taiwan. [Lin, Jing; Huang, Peng] Shenzhen Univ, Sch Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoud, Shenzhen 518060, Peoples R China. [Liao, Hsien-Shun; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Liao, Hsien-Shun; Jin, Albert] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. [Liu, Yang] Duke Univ, Dept Biomed Engn, Fitzpatrick Inst Photon, Durham, NC 27708 USA. RP Huang, P (reprint author), Shenzhen Univ, Sch Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoud, Shenzhen 518060, Peoples R China.; Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.; Jin, A (reprint author), NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. EM peng.huang@szu.edu.cn; jina@mail.nih.gov; shawn.chen@nih.gov RI Huang, Peng/R-2480-2016 OI Huang, Peng/0000-0003-3651-7813 FU startup fund from the Shenzhen University; National Natural Science Foundation of China [81401465, 51573096]; Intramural Research Program (IRP) of the NIBIB/NIH FX This work was supported by the startup fund from the Shenzhen University, the National Natural Science Foundation of China (81401465, 51573096), and the Intramural Research Program (IRP) of the NIBIB/NIH. NR 47 TC 2 Z9 2 U1 17 U2 19 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2016 VL 8 IS 31 BP 14814 EP 14820 DI 10.1039/c6nr04672j PG 7 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA DT4ID UT WOS:000381442500015 PM 27447093 ER PT J AU Geiger, JT Arthur, KC Dawson, TM Rosenthal, LS Pantelyat, A Albert, M Hillis, AE Crain, B Pletnikova, O Troncoso, JC Scholz, SW AF Geiger, Joshua T. Arthur, Karissa C. Dawson, Ted M. Rosenthal, Liana S. Pantelyat, Alexander Albert, Marilyn Hillis, Argye E. Crain, Barbara Pletnikova, Olga Troncoso, Juan C. Scholz, Sonja W. TI C9orf72 Hexanucleotide Repeat Analysis in Cases with Pathologically Confirmed Dementia with Lewy Bodies SO NEURODEGENERATIVE DISEASES LA English DT Article DE Dementia with Lewy bodies; Amyotrophic lateral sclerosis; Frontotemporal dementia; C9orf72; Hexanucleotide; repeat expansion ID FRONTOTEMPORAL DEMENTIA; EXPANSION; DISEASE; PSYCHOSIS; PARKINSONISM; DIAGNOSIS; MUTATION; DLB; FTD; ALS AB Background: Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia affecting the elderly. The GGGGCC hexanucleotide expansion mutation at the C9orf72 locus has been identified as a major cause of amyotrophic lateral sclerosis and frontotemporal dementia, raising the question of whether this mutation is a factor in DLB. Furthermore, a small number of clinically diagnosed DLB patients have previously been reported to carry the pathologic C9orf72 hexanucleotide repeat expansion. Objective: To explore whether the C9orf72 mutation is present in pathologically confirmed DLB patients. Methods: We screened a cohort of 111 definite DLB cases with extensive Lewy body pathology for the C9orf72 hexanucleotide repeat expansion using the repeat-primed polymerase chain reaction assay. Results: No pathogenic expansions of the C9orf72 hexanucleotide repeat were found, suggesting that there is no causal relationship between C9orf72 and DLB. Conclusion: Our data illustrate that C9orf72 screening of clinically diagnosed DLB patients should only be considered in cases with a family history of motor neuron disease or frontotemporal dementia to distinguish between mimic diseases. (C) 2016 S. Karger AG, Basel C1 [Geiger, Joshua T.; Scholz, Sonja W.] NINDS, Neurodegenerat Dis Res Unit, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Arthur, Karissa C.] NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Arthur, Karissa C.] Commonwealth Med Coll, Scranton, PA USA. [Dawson, Ted M.; Rosenthal, Liana S.; Pantelyat, Alexander; Albert, Marilyn; Hillis, Argye E.; Troncoso, Juan C.; Scholz, Sonja W.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Solomon H Synder Dept Neurosci, Baltimore, MD USA. [Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Neuroregenerat Program, Baltimore, MD USA. [Crain, Barbara; Pletnikova, Olga; Troncoso, Juan C.] Johns Hopkins Univ, Dept Pathol Neuropathol, Baltimore, MD USA. RP Geiger, JT (reprint author), Porter Neurosci Res Ctr, Neurodegenerat Dis Res Unit, Bldg 35,Room 1A-1000, Bethesda, MD 20892 USA. EM geigerjt@ninds.nih.gov FU US National Institutes of Health (National Institute on Aging, National Institute of Neurological Disorders and Stroke) [Z01-AG000949]; NIH; National Institute of Neurological Disorders and Stroke [R25 NS065729] FX J.T.G., K.C.A. and S.W.S report that this work was supported (in part) by the Intramural Research Program of the US National Institutes of Health (National Institute on Aging, National Institute of Neurological Disorders and Stroke) (Z01-AG000949). K.C.A. reports that this research was also 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 the Doris Duke Charitable Foundation, the Howard Hughes Medical Institute, the American Association for Dental Research, the Colgate-Palmolive Company and other private donors. For a complete list, visit the Foundation website at http://www.fnih.org. S.W.S. received a R25 career development grant from the National Institute of Neurological Disorders and Stroke (R25 NS065729). DNA from brain tissue samples was provided by the Johns Hopkins Morris K. Udall Center for Parkinson's Disease Research Center of Excellence (NIH P50 NS38377) and the Johns Hopkins Alzheimer Disease Research Center (NIH P50 AG05146). T.M.D. is the Leonard and Madlyn Abramson Professor in Neurodegenerative Disease. NR 16 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 EI 1660-2862 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2016 VL 16 IS 5-6 BP 370 EP 372 DI 10.1159/000445872 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV8VQ UT WOS:000383215200010 PM 27241037 ER PT J AU Fraidakis, MJ Brunetti, M Blackstone, C Filippi, M Chio, A AF Fraidakis, Matthew J. Brunetti, Maura Blackstone, Craig Filippi, Massimo Chio, Adriano TI Novel Compound Heterozygous Spatacsin Mutations in a Greek Kindred with Hereditary Spastic Paraplegia SPG11 and Dementia SO NEURODEGENERATIVE DISEASES LA English DT Article DE Diffusion tensor imaging; Hereditary spastic paraparesis; Leukoencephalopathy; Neurogenetics; Spatacsin ID THIN CORPUS-CALLOSUM; AMYOTROPHIC-LATERAL-SCLEROSIS; GENETIC-HETEROGENEITY; AUTOSOMAL-DOMINANT; MENTAL IMPAIRMENT; PARAPARESIS; DELETION; IDENTIFICATION; EPIDEMIOLOGY; DEGENERATION AB SPG11 belongs to the autosomal recessive hereditary spastic paraplegias (HSP) and presents during childhood or puberty with a complex clinical phenotype encompassing learning difficulties, ataxia, peripheral neuropathy, amyotrophy, and mental retardation. We hereby present the case of a 30-year old female patient with complex autosomal recessive HSP with thinning of the corpus callosum (TCC) and dementia that was compound heterozygous with two novel mutations in the SPG11 gene. Sequence analysis of the SPG11 gene revealed two novel mutations in a compound heterozygous state in the index patient (c.2431C>T/p.Gln811Ter and c.6755_6756insT/p.Glu2252Aspfs*88). MRI showed abnormal TCC, white matter (WM) hyperintensities periventricularly, and the 'ears of the lynx' sign. Diffusion tensor imaging showed a mild-to-moderate decrease in fractional anisotropy and an increase in mean diffusivity in WM compared to age-matched controls, while magnetic resonance spectroscopy showed abnormal findings in affected WM with a decrease in N-acetyl-aspartate in WM regions of interest. This is the first SPG11 kindred from the Greek population to be reported in the medical literature. (C) 2016 S. Karger AG, Basel C1 [Fraidakis, Matthew J.] NEURORARE Ctr Rare & Genet Neurol & Neuromuscular, GR-14561 Athens, Greece. [Blackstone, Craig] NINDS, Cell Biol Sect, Neurogenet Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Filippi, Massimo] Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Div Neurosci, Neuroimaging Res Unit,Inst Expt Neurol, Milan, Italy. [Brunetti, Maura] Azienda Osped Citta Salute & Sci, Dept Clin Pathol, Mol Genet Unit, Turin, Italy. [Chio, Adriano] Univ Turin, Dept Neurosci Rita Levi Montalcini, Turin, Italy. [Chio, Adriano] Neurosci Inst Turin NIT, Turin, Italy. RP Fraidakis, MJ (reprint author), NEURORARE Ctr Rare & Genet Neurol & Neuromuscular, GR-14561 Athens, Greece. EM mjfraidakis@neurorare.gr NR 61 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 EI 1660-2862 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2016 VL 16 IS 5-6 BP 373 EP 381 DI 10.1159/000444715 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV8VQ UT WOS:000383215200011 PM 27318863 ER PT J AU Zhovmer, A Qu, XH AF Zhovmer, Alexander Qu, Xiaohui TI Proximal disruptor aided ligation (ProDAL) of kilobase-long RNAs SO RNA BIOLOGY LA English DT Article DE DNA disruptor for ligation; long RNA probes; RNA labeling; splint ligation; site-specific RNA modification ID TETRAHYMENA RIBOZYME; SPLINTED LIGATION; SITE; TRANSLATION; SPECIFICITY; HYDROLYSIS; DOMAINS; DNA AB RNA with site-specific modification is a useful tool for RNA biology studies. However, generating kilobase (kb) -long RNA with internal modification at a site distant from RNA termini remains challenging. Here we report an enhanced splint ligation technique, proximal disruptor aided ligation (ProDAL), which allows adequate efficiency toward this purpose. The key to our approach is using multiple DNA oligonucleotides, 'proximal disruptors', to target the RNA substrate sequence next to the ligation site. The binding of disruptors helps to free the ligation site from intramolecular RNA basepairing, and consequently promotes more efficient formation of the pre-ligation complex and a higher overall ligation yield. We used naturally occurring 1.0 kb renilla and 1.9 kb firefly luciferase mRNA sequences to test the efficacy of our approach. ProDAL yielded 9-14% efficiency for the ligation between two RNA substrates, both of which were between 414 and 1313 nucleotides (nt) long. ProDAL also allowed similarly high efficiency for generating kb-long RNA with site-specific internal modification by a simple three-part ligation between two long RNA substrates and a modification-carrying RNA oligonucleotide. In comparison, classical splint ligation yielded a significantly lower efficiency of 0-2% in all cases. We expect that ProDAL will benefit studies involving kb-long RNAs, including translation, long non-coding RNAs, RNA splicing and modification, and large ribonucleoprotein complexes. C1 [Zhovmer, Alexander; Qu, Xiaohui] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. [Zhovmer, Alexander] NHLBI, Genet & Dev Biol Ctr, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Qu, XH (reprint author), Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. EM qux@mskcc.org FU Memorial Sloan Kettering Cancer Center Support Grant/Core Grant [P30 CA008748] FX This research was supported by the Memorial Sloan Kettering Cancer Center Support Grant/Core Grant (P30 CA008748). NR 34 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1547-6286 EI 1555-8584 J9 RNA BIOL JI RNA Biol. PY 2016 VL 13 IS 7 BP 613 EP 621 DI 10.1080/15476286.2016.1189072 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DV5IC UT WOS:000382959500002 PM 27211284 ER PT J AU Cascajo, MV Abdelmohsen, K Noh, JH Fernandez-Ayala, DJM Willers, IM Brea, G Lopez-Lluch, G Valenzuela-Villatoro, M Cuezva, JM Gorospe, M Siendones, E Navas, P AF Cascajo, Maria V. Abdelmohsen, Kotb Noh, Ji Heon Fernandez-Ayala, Daniel J. M. Willers, Imke M. Brea, Gloria Lopez-Lluch, Guillermo Valenzuela-Villatoro, Marina Cuezva, Jose M. Gorospe, Myriam Siendones, Emilio Navas, Placido TI RNA-binding proteins regulate cell respiration and coenzyme Q biosynthesis by post-transcriptional regulation of COQ7 SO RNA BIOLOGY LA English DT Article DE COQ7; coenzyme Q10; hnRNP C1/C2; HuR; mitochondrial respiration; post-transcriptional regulation; RNA-binding proteins ID MESSENGER-RNA; UBIQUINONE BIOSYNTHESIS; SACCHAROMYCES-CEREVISIAE; CAENORHABDITIS-ELEGANS; UNTRANSLATED REGION; Q(10) DEFICIENCY; LIFE-SPAN; HUR; EXPRESSION; AUF1 AB Coenzyme Q (CoQ) is a key component of the mitochondrial respiratory chain carrying electrons from complexes I and II to complex III and it is an intrinsic component of the respirasome. CoQ concentration is highly regulated in cells in order to adapt the metabolism of the cell to challenges of nutrient availability and stress stimuli. At least 10 proteins have been shown to be required for CoQ biosynthesis in a multi-peptide complex and COQ7 is a central regulatory factor of this pathway. We found that the first 765 bp of the 30-untranslated region (UTR) of COQ7 mRNA contains cis-acting elements of interaction with RNA-binding proteins (RBPs) HuR and hnRNP C1/C2. Binding of hnRNP C1/C2 to COQ7 mRNA was found to require the presence of HuR, and hnRNP C1/C2 silencing appeared to stabilize COQ7 mRNA modestly. By contrast, lowering HuR levels by silencing or depriving cells of serum destabilized and reduced the half-life of COQ7 mRNA, thereby reducing COQ7 protein and CoQ biosynthesis rate. Accordingly, HuR knockdown decreased oxygen consumption rate and mitochondrial production of ATP, and increased lactate levels. Taken together, our results indicate that a reduction in COQ7 mRNA levels by HuR depletion causes mitochondrial dysfunction and a switch toward an enhanced aerobic glycolysis, the characteristic phenotype exhibited by primary deficiency of CoQ(10). Thus HuR contributes to efficient oxidative phosphorylation by regulating of CoQ(10) biosynthesis. C1 [Cascajo, Maria V.; Fernandez-Ayala, Daniel J. M.; Brea, Gloria; Lopez-Lluch, Guillermo; Valenzuela-Villatoro, Marina; Siendones, Emilio; Navas, Placido] Univ Pablo de Olavide, Ctr Andaluz Biol Desarrollo, CSIC, JA, Seville, Spain. [Cascajo, Maria V.; Fernandez-Ayala, Daniel J. M.; Brea, Gloria; Lopez-Lluch, Guillermo; Valenzuela-Villatoro, Marina; Siendones, Emilio; Navas, Placido] ISCIII, Ctr Biomed Res Rare Dis CIBERER, Seville, Spain. [Abdelmohsen, Kotb; Noh, Ji Heon; Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Willers, Imke M.; Cuezva, Jose M.] Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, Dept Biol Mol, Madrid, Spain. [Willers, Imke M.; Cuezva, Jose M.] ISCIII, Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain. RP Navas, P (reprint author), Univ Pablo de Olavide, Ctr Andaluz Biol Desarrollo, CSIC, JA, Seville, Spain.; Navas, P (reprint author), ISCIII, Ctr Biomed Res Rare Dis CIBERER, Seville, Spain. EM pnavas@upo.es OI Fernandez-Ayala, Daniel Jose Moreno/0000-0001-8176-1431 FU Spanish Ministry of Health, Instituto de Salud Carlos III (ISCIII) [FIS PI14-01962]; Spanish Ministry of Economy and Competitively [SAF2013-41945-R]; Intramural Research Program of the NIA, NIH FX This research was supported by grants from the Spanish Ministry of Health, Instituto de Salud Carlos III (ISCIII), FIS PI14-01962 to PN, the Spanish Ministry of Economy and Competitively, SAF2013-41945-R to JMC, and the Intramural Research Program of the NIA, NIH (KA, MG). NR 68 TC 1 Z9 1 U1 3 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1547-6286 EI 1555-8584 J9 RNA BIOL JI RNA Biol. PY 2016 VL 13 IS 7 BP 622 EP 634 DI 10.1080/15476286.2015.1119366 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DV5IC UT WOS:000382959500003 PM 26690054 ER PT J AU Raouf, J Kirkby, N Ahmetaj-Shala, B Liu, B Mres, SM Korotkova, M Zeldin, D Zhou, Y Jakobsson, PJ Mitchell, J AF Raouf, J. Kirkby, N. Ahmetaj-Shala, B. Liu, B. MRes, S. M. Korotkova, M. Zeldin, D. Zhou, Y. Jakobsson, P-J Mitchell, J. TI mPGES-1 deletion increases prostacyclin and evades the elevated systemic ADMA associatedwith COX-2 inhibitors: relevance to cardiovascular safety of mPGES-1 inhibitors SO SCANDINAVIAN JOURNAL OF RHEUMATOLOGY LA English DT Meeting Abstract C1 [Raouf, J.; Korotkova, M.; Jakobsson, P-J] Karolinska Inst, S-10401 Stockholm, Sweden. [Kirkby, N.; Ahmetaj-Shala, B.; MRes, S. M.; Mitchell, J.] Imperial Coll London, London, England. [Liu, B.; Zhou, Y.] Shantou Univ, Coll Med, Shantou, Peoples R China. [Zeldin, D.] NIEHS, Davis, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0300-9742 EI 1502-7732 J9 SCAND J RHEUMATOL JI Scand. J. Rheumatol. PY 2016 VL 45 SU 128 MA PP26 BP 24 EP 25 PG 2 WC Rheumatology SC Rheumatology GA DV0AF UT WOS:000382578900043 ER PT S AU Lu, L Wu, DJ Lay, N Liu, D Nogues, I Summers, RM AF Lu, Le Wu, Dijia Lay, Nathan Liu, David Nogues, Isabella Summers, Ronald M. GP IEEE TI Accurate 3D Bone Segmentation in Challenging CT Images: Bottom-up Parsing and Contextualized Optimization SO 2016 IEEE WINTER CONFERENCE ON APPLICATIONS OF COMPUTER VISION (WACV 2016) SE IEEE Winter Conference on Applications of Computer Vision LA English DT Proceedings Paper CT IEEE Winter Conference on Applications of Computer Vision (WACV) CY MAR 07-10, 2016 CL Lake Placid, NY SP IEEE ID VOXEL CLASSIFICATION; GRAPH CUTS; IDENTIFICATION; FEATURES; SUBJECT; ANATOMY AB In full or arbitrary field-of-view (FOV) 3D CT imaging, obtaining an accurate per-voxel segmentation for complete large and small bones remains an unsolved and challenging problem. The difficulty lies in the notable variation in appearance and position observed among cortical bones, marrow and pathologies. To approach this problem, several studies have employed active shape models and atlas models. In this paper, we argue that a bottom-up approach, defined by classifying and grouping supervoxels, is another viable technique. Moreover, it can be integrated into a conditional random field (CRF) representation. Our approach consists of the following steps: first, an input CT volume is decomposed into supervoxels, in order to ensure very high bone boundary recall. Supervoxels are generated via a robust process of conservative region partitioning and recursive region merging. In order to maximize sparsity and classification efficiency, we use a Bayesian sparse linear classifier to compute and optimize middle-level image features. Next, we disambiguate the CRF unary potentials via contextualized optimization by pooling over selective supervoxel pairs. Finally, we adopt a pairwise support vector machine (SVM) model to learn the CRF pairwise potential in a fully supervised manner. We evaluate our method quantitatively on 137 low-resolution, low-contrast CT volumes with severe imaging noise, among which various bone pathologies are represented. Our system proves to be efficient; it achieves a clinically significant segmentation accuracy level (Dice Coefficient 98.2 %). C1 [Lu, Le; Wu, Dijia; Lay, Nathan; Liu, David] NIH, Bldg 10, Bethesda, MD 20892 USA. [Nogues, Isabella] Google Inc, Mountain View, CA USA. [Summers, Ronald M.] Siemens Healthcare, Erlangen, Germany. RP Lu, L (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM le.lu@nih.gov NR 52 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2472-6737 BN 978-1-5090-0641-0 J9 IEEE WINT CONF APPL PY 2016 PG 10 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Optics SC Computer Science; Engineering; Optics GA BF5UY UT WOS:000382670200060 ER PT J AU Lloyd, GR Oza, S Kozey-Keadle, S Pellegrini, CA Conroy, DE Penedo, FJ Spring, BJ Phillips, SM AF Lloyd, Gillian R. Oza, Sonal Kozey-Keadle, Sarah Pellegrini, Christine A. Conroy, David E. Penedo, Frank J. Spring, Bonnie J. Phillips, Siobhan M. TI Breast Cancer Survivors' Beliefs and Preferences Regarding Technology-Supported Sedentary Behavior Reduction Interventions SO AIMS PUBLIC HEALTH LA English DT Article DE sedentary behavior; technology; interventions; breast cancer survivors ID QUALITY-OF-LIFE; ASSESSED PHYSICAL-ACTIVITY; OLDER-ADULTS; INTENSITY ACTIVITY; TIME; HEALTH; ASSOCIATIONS; VALIDITY; RECOMMENDATIONS; RELIABILITY AB Purpose: Less time spent in sedentary behaviors is associated with improved health and disease outcomes in breast cancer survivors. However, little is known about survivors' interest in sedentary behavior reduction interventions and how to effectively reduce this risk behavior. The purpose of this study was to explore breast cancer survivors' interest in and preferences for technology-supported sedentary behavior reduction interventions. Methods: Breast cancer survivors (n = 279; M-age = 60.7 (SD = 9.7)) completed a battery of online questionnaires. Descriptive statistics were calculated for all data. To examine potential relationships between demographic, disease and behavioral factors, and survivors' interest in a technology-supported sedentary behavior reduction intervention, we conducted logistic regression analyses. These same factors were examined in relation to the perceptions of the effectiveness of such intervention using multiple regression analyses. Results: On average, survivors spent 10.1 (SD = 4.3) hours/day in sedentary activity. They believed prolonged periods of sedentary behavior were harmful to their health (87.0%) and that reducing sedentary behavior could improve their health (88.4%). Survivors believed they should move around after 30-60 (56.7%) or >= 60 (29.9%) minutes of sedentary behavior and indicated they were most likely to replace sedentary behaviors with walking around (97.1%) or walking in place (73.4%). The majority of survivors (79.9%) was interested in participating in a technology-supported sedentary behavior reduction intervention and indicated they would use a smartphone application (61.3%) 2-3 times/day (48.0%), 6 to 7 days/week (52.0%). Most survivors (73.5%) believed reminders would help them decrease sedentary behavior and preferred they be delivered after sitting for 60 minutes (60.5%) via vibrations on a wrist worn activity tracker (77.3%) or text messages (54.4%). Conclusions: Technology-supported sedentary behavior reduction interventions may be feasible and acceptable to breast cancer survivors. Data regarding user preferences for content, features, delivery mode and design will aid researchers in developing sedentary interventions that are potentially more relevant and effective from the outset. C1 [Lloyd, Gillian R.; Pellegrini, Christine A.; Conroy, David E.; Spring, Bonnie J.; Phillips, Siobhan M.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Oza, Sonal] Northwestern Univ, Dept Phys Med & Rehabil, Feinberg Sch Med, Chicago, IL 60611 USA. [Kozey-Keadle, Sarah] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Conroy, David E.] Penn State Univ, Dept Kinesiol, University Pk, PA 16802 USA. [Penedo, Frank J.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. RP Phillips, SM (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. EM smphillips@northwestern.edu NR 73 TC 0 Z9 0 U1 5 U2 5 PU AMER INST MATHEMATICAL SCIENCES-AIMS PI SPRINGFIELD PA PO BOX 2604, SPRINGFIELD, MO 65801-2604 USA SN 2327-8994 J9 AIMS PUBLIC HEALTH JI AIMS Public Health PY 2016 VL 3 IS 3 BP 592 EP 614 DI 10.3934/publichealth.2016.3.592 PG 23 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DU8TQ UT WOS:000382488300013 ER PT S AU Stoffels, M Kastner, DL AF Stoffels, Monique Kastner, Daniel L. BE Chakravarti, A Green, E TI Old Dogs, New Tricks: Monogenic Autoinflammatory Disease Unleashed SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 17 SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE DADA2; macrophage activation syndrome; SAVI; Schnitzler syndrome; PRAAS; HA20 ID FAMILIAL MEDITERRANEAN FEVER; CYCLIC GMP-AMP; MACROPHAGE ACTIVATION SYNDROME; NF-KAPPA-B; MEVALONATE KINASE-DEFICIENCY; ONSET STILLS-DISEASE; CYTOSOLIC-DNA; ARTICULAR SYNDROME; SOMATIC MOSAICISM; COLCHICINE-RESISTANT AB Autoinflammatory diseases are inborn disorders of the innate immune system characterized by episodes of systemic inflammation that are mediated largely by myeloid cells. The field of autoinflammatory diseases has been established since 1999, following the identification of the first genes underlying periodic fever syndromes. This review focuses on developments that have transformed the field in the last two years. We discuss three newly described monogenic autoinflammatory diseases [deficiency of adenosine deaminase 2 (DADA2), a subtype of macrophage activation syndrome (MAS), and stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI)], discuss the possibilities of somatic mosaicism and digenic inheritance, and give an update on new concepts in pathways involved in familial Mediterranean fever (FMF). Finally, the new monogenic autoinflammatory disease haploinsufficiency of A20 (HA20) underscores the placement of monogenic diseases in the firmament of common autoinflammatory phenotypes. The advances in the last two years have shed light on the pathophysiology of several autoinflammatory diseases and have elucidated new pathways that play a role in innate immunity. C1 [Stoffels, Monique; Kastner, Daniel L.] NHGRI, Metab Cardiovasc & Inflammatory Dis Genom Branch, NIH, Bethesda, MD 20892 USA. RP Kastner, DL (reprint author), NHGRI, Metab Cardiovasc & Inflammatory Dis Genom Branch, NIH, Bethesda, MD 20892 USA. EM kastnerd@mail.nih.gov NR 146 TC 2 Z9 2 U1 3 U2 4 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1527-8204 BN 978-0-8243-3717-9 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2016 VL 17 BP 245 EP 272 DI 10.1146/annurev-genom-090413-025334 PG 28 WC Genetics & Heredity SC Genetics & Heredity GA BF5TB UT WOS:000382615800012 PM 27362340 ER PT J AU Pastore, N Brady, OA Diab, HI Martina, JA Sun, L Huynh, T Lim, JA Zare, H Raben, N Ballabio, A Puertollano, R AF Pastore, Nunzia Brady, Owen A. Diab, Heba I. Martina, Jose A. Sun, Lu Tuong Huynh Lim, Jeong-A Zare, Hossein Raben, Nina Ballabio, Andrea Puertollano, Rosa TI TFEB and TFE3 cooperate in the regulation of the innate immune response in activated macrophages SO AUTOPHAGY LA English DT Article DE autophagy; immune response; macrophages; Tfe3; Tfeb ID TRANSCRIPTION FACTOR; LYSOSOMAL BIOGENESIS; BACTERIAL PATHOGENS; PROBE LEVEL; IN-VIVO; AUTOPHAGY; MTORC1; PATHWAYS; FAMILY; CELLS AB The activation of transcription factors is critical to ensure an effective defense against pathogens. In this study we identify a critical and complementary role of the transcription factors TFEB and TFE3 in innate immune response. By using a combination of chromatin immunoprecipitation, CRISPR-Cas9-mediated genome-editing technology, and in vivo models, we determined that TFEB and TFE3 collaborate with each other in activated macrophages and microglia to promote efficient autophagy induction, increased lysosomal biogenesis, and transcriptional upregulation of numerous proinflammatory cytokines. Furthermore, secretion of key mediators of the inflammatory response (CSF2, IL1B, IL2, and IL27), macrophage differentiation (CSF1), and macrophage infiltration and migration to sites of inflammation (CCL2) was significantly reduced in TFEB and TFE3 deficient cells. These new insights provide us with a deeper understanding of the transcriptional regulation of the innate immune response. C1 [Pastore, Nunzia; Tuong Huynh; Ballabio, Andrea] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Pastore, Nunzia; Tuong Huynh; Ballabio, Andrea] Texas Children Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX USA. [Brady, Owen A.; Diab, Heba I.; Martina, Jose A.; Sun, Lu; Puertollano, Rosa] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. [Lim, Jeong-A; Zare, Hossein; Raben, Nina] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA. [Ballabio, Andrea] Telethon Inst Genet & Med TIGEM, Via Campi Flegrei 34, I-80078 Naples, Italy. [Ballabio, Andrea] Univ Naples Federico II, Dept Translat Med, Med Genet, Naples, Italy. RP Ballabio, A (reprint author), Telethon Inst Genet & Med TIGEM, Via Campi Flegrei 34, I-80078 Naples, Italy.; Puertollano, R (reprint author), NHLBI, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM ballabio@tigem.it; puertolr@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI); Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin diseases (NIAMS) of the NIH; CRADA; US National Institutes of Health [R01-NS078072]; Beyond Batten Disease Foundation FX O.B., H.D., J.M., L.S., and R.P. were supported by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI). L.J., H.Z., and N.R. were supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin diseases (NIAMS) of the NIH and a CRADA between NIH and Genzyme Corporation. N.P., T.H. and A.B. were supported by US National Institutes of Health (R01-NS078072) and by the Beyond Batten Disease Foundation. NR 48 TC 2 Z9 2 U1 3 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PY 2016 VL 12 IS 8 BP 1240 EP 1258 DI 10.1080/15548627.2016.1179405 PG 19 WC Cell Biology SC Cell Biology GA DU6FI UT WOS:000382309200003 PM 27171064 ER PT J AU Velma, V Dasari, SR Tchounwou, PB AF Velma, Venkatramreddy Dasari, Shaloam R. Tchounwou, Paul B. TI Low Doses of Cisplatin Induce Gene Alterations, Cell Cycle Arrest, and Apoptosis in Human Promyelocytic Leukemia Cells SO BIOMARKER INSIGHTS LA English DT Article DE cisplatin; HL-60 cells; RNA sequencing; cell cycle; apoptosis ID ANAPHASE-PROMOTING COMPLEX; PHASE-II TRIAL; BREAST-CANCER; MOLECULAR-MECHANISMS; OVARIAN-CANCER; DNA-REPLICATION; PIF1 HELICASE; IN-VIVO; CHEMOTHERAPY; EXPRESSION AB Cisplatin is a known antitumor drug, but its mechanisms of action are not fully elucidated. In this research, we studied the anticancer potential of cisplatin at doses of 1, 2, or 3 mu M using HL-60 cells as a test model. We investigated cisplatin effects at the molecular level using RNA sequencing, cell cycle analysis, and apoptotic assay after 24, 48, 72, and 96 hours of treatment. The results show that many genes responsible for molecular and cellular functions were significantly altered. Cisplatin treatment also caused the cells to be arrested at the DNA synthesis phase, and as the time increases, the cells gradually accumulated at the sub-G1 phase. Also, as the dose increases, a significant number of cells entered into the apoptotic and necrotic stages. Altogether, the data show that low doses of cisplatin significantly impact the viability of HL-60 cells, through modulation of gene expression, cell cycle, and apoptosis. C1 [Velma, Venkatramreddy; Dasari, Shaloam R.; Tchounwou, Paul B.] Jackson State Univ, Coll Sci Engn & Technol, NIH NIMHD RCMI Ctr Environm Hlth, Cell & Toxicogenom Res Lab, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIH NIMHD RCMI Ctr Environm Hlth, Cell & Toxicogenom Res Lab, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU NIMHD NIH HHS [G12 MD007581] NR 66 TC 1 Z9 1 U1 1 U2 1 PU LIBERTAS ACAD PI AUCKLAND PA PO BOX 300-874, ALBANY 0752, AUCKLAND, 00000, NEW ZEALAND SN 1177-2719 J9 BIOMARK INSIGHTS JI Biomark. Insights PY 2016 VL 11 BP 113 EP 121 DI 10.4137/BMIMI.S39445 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DU4ZR UT WOS:000382222100001 PM 27594783 ER PT J AU Taylor, DA Perin, EC Willerson, JT Zierold, C Resende, M Carlson, M Nestor, B Wise, E Orozco, A Pepine, CJ Henry, TD Ellis, SG Zhao, DXM Traverse, JH Cooke, JP Schutt, RC Bhatnagar, A Grant, MB Lai, DJ Johnstone, BH Sayre, SL Moye, L Ebert, RF Bolli, R Simari, RD Cogle, CR AF Taylor, Doris A. Perin, Emerson C. Willerson, James T. Zierold, Claudia Resende, Micheline Carlson, Marjorie Nestor, Belinda Wise, Elizabeth Orozco, Aaron Pepine, Carl J. Henry, Timothy D. Ellis, Stephen G. Zhao, David X. M. Traverse, Jay H. Cooke, John P. Schutt, Robert C. Bhatnagar, Aruni Grant, Maria B. Lai, Dejian Johnstone, Brian H. Sayre, Shelly L. Moye, Lem Ebert, Ray F. Bolli, Roberto Simari, Robert D. Cogle, Christopher R. CA Cardiovasc Cell Therapy Res Networ TI Identification of Bone Marrow Cell Subpopulations Associated With Improved Functional Outcomes in Patients With Chronic Left Ventricular Dysfunction: An Embedded Cohort Evaluation of the FOCUS-CCTRN Trial SO CELL TRANSPLANTATION LA English DT Article DE Bone marrow; Heart failure; Ischemic cardiomyopathy; Stem cells; Cell therapy ID ENDOTHELIAL PROGENITOR CELLS; ACUTE MYOCARDIAL-INFARCTION; ISCHEMIC-HEART-DISEASE; RESEARCH NETWORK CCTRN; MONONUCLEAR-CELLS; RANDOMIZED-TRIAL; STEM-CELLS; THERAPY; DELIVERY; BLOOD AB In the current study, we sought to identify bone marrow-derived mononuclear cell (BM-MNC) subpopulations associated with a combined improvement in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and maximal oxygen consumption (VO2 max) in patients with chronic ischemic cardiomyopathy 6 months after receiving transendocardial injections of autologous BM-MNCs or placebo. For this prospectively planned analysis, we conducted an embedded cohort study comprising 78 patients from the FOCUS-Cardiovascular Cell Therapy Research Network (CCTRN) trial. Baseline BM-MNC immunophenotypes and progenitor cell activity were determined by flow cytometry and colony-forming assays, respectively. Previously stable patients who demonstrated improvement in LVEF, LVESV, and VO2 max during the 6-month course of the FOCUS-CCTRN study (group 1, n = 17) were compared to those who showed no change or worsened in one to three of these endpoints (group 2, n = 61) and to a subset of patients from group 2 who declined in all three functional endpoints (group 2A, n = 11). Group 1 had higher frequencies of B-cell and CXCR4(+) BM-MNC subpopulations at study baseline than group 2 or 2A. Furthermore, patients in group 1 had fewer endothelial colony-forming cells and monocytes/macrophages in their bone marrow than those in group 2A. To our knowledge, this is the first study to show that in patients with ischemic cardiomyopathy, certain bone marrow-derived cell subsets are associated with improvement in LVEF, LVESV, and VO2 max at 6 months. These results suggest that the presence of both progenitor and immune cell populations in the bone marrow may influence the natural history of chronic ischemic cardiomyopathy-even in stable patients. Thus, it may be important to consider the bone marrow composition and associated regenerative capacity of patients when assigning them to treatment groups and evaluating the results of cell therapy trials. C1 [Taylor, Doris A.; Perin, Emerson C.; Willerson, James T.; Resende, Micheline; Nestor, Belinda; Orozco, Aaron] CHI St Lukes Hlth, Texas Heart Inst, Houston, TX 77030 USA. [Zierold, Claudia; Carlson, Marjorie] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Wise, Elizabeth; Pepine, Carl J.; Grant, Maria B.; Cogle, Christopher R.] Univ Florida, Coll Med, Gainesville, FL 32610 USA. [Henry, Timothy D.] Cedars Sinai Heart Inst, Los Angeles, CA USA. [Henry, Timothy D.; Traverse, Jay H.] Minneapolis Heart Inst Fdn Abbott, Minneapolis, MN USA. [Ellis, Stephen G.] Cleveland Clin Fdn, Cleveland, OH USA. [Zhao, David X. M.] Wake Forest Sch Med, Winston Salem, NC USA. [Cooke, John P.; Schutt, Robert C.] Houston Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA. [Cooke, John P.; Schutt, Robert C.] Houston Methodist Res Inst, Houston, TX USA. [Bhatnagar, Aruni] Univ Louisville, Louisville, KY USA. [Lai, Dejian; Sayre, Shelly L.; Moye, Lem] Univ Texas Houston, Sch Publ Hlth, 1200 Herman Pressler,E-1009, Houston, TX 77030 USA. [Johnstone, Brian H.] Indiana Univ Sch Med, Indianapolis, IN USA. [Ebert, Ray F.] NHLBI, Bethesda, MD USA. [Simari, Robert D.] Univ Kansas, Sch Med, Kansas City, KS 66160 USA. RP Moye, L (reprint author), Univ Texas Houston, Sch Publ Hlth, 1200 Herman Pressler,E-1009, Houston, TX 77030 USA. EM Lemmoye@msn.com OI Cooke, John/0000-0003-0033-9138 FU National Heart, Lung, and Blood Institute [5 UM1 HL087318, N01 HB 37164, HHSN268201000008C]; National Center for Research Resources CTSA grant [UL1 TR000064]; Texas State Legislature; CCTRN; [N01 HB 37163]; [HHSN268201000007C] FX This work was supported by the National Heart, Lung, and Blood Institute under cooperative agreement 5 UM1 HL087318, and also, in part, by the National Heart, Lung, and Blood Institute by contracts N01 HB 37164 and HHSN268201000008C, which were awarded to the Molecular and Cellular Therapeutics Facility, University of Minnesota, and by contracts N01 HB 37163 and HHSN268201000007C, which were awarded to the Cell Processing Facility, Baylor College of Medicine. Further funding was provided by the National Center for Research Resources CTSA grant UL1 TR000064 awarded to the University of Florida. Funding from the Texas State Legislature was also used to assist investigators at the Texas Heart Institute, Houston, Texas. The CCTRN acknowledges its industry partners, Biosafe, Biologics Delivery System Group, and Cordis Corporation, for their contributions of equipment and technical support during the conduct of the trial. We also acknowledge Dr. Sonia Skarlatos (1953-2013) for her insight, expertise, and support of the CCTRN, which continues to propel the cell therapy field forward. In addition, we thank Dr. Ke Li of the Texas Heart Institute for creation of the heat map. The opinions expressed in this report do not necessarily reflect those of the National Heart, Lung, and Blood Institute, the NIH, or the US Department of Health and Human Services. The authors declare no conflicts of interest. NR 31 TC 1 Z9 1 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2016 VL 25 IS 9 SI SI BP 1675 EP 1687 DI 10.3727/096368915X689901 PG 13 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA DV3DD UT WOS:000382800300009 PM 26590374 ER PT J AU Yoshino, A Polouliakh, N Meguro, A Takeuchi, M Kawagoe, T Mizuki, N AF Yoshino, Atsushi Polouliakh, Natalia Meguro, Akira Takeuchi, Masaki Kawagoe, Tatsukata Mizuki, Nobuhisa TI Chum salmon egg extracts induce upregulation of collagen type I and exert antioxidative effects on human dermal fibroblast cultures SO CLINICAL INTERVENTIONS IN AGING LA English DT Article DE fish egg; antiaging; gene expression analysis; antioxidative gene; phylogenetic footprinting analysis ID OXIDATIVE STRESS; HUMAN SKIN; ULTRAVIOLET-IRRADIATION; CLINICAL-EFFICACY; ESTROGEN; EXPRESSION; RECEPTOR; PROTECTION; PATHWAY; GENES AB Components of fish roe possess antioxidant and antiaging activities, making them potentially very beneficial natural resources. Here, we investigated chum salmon eggs (CSEs) as a source of active ingredients, including vitamins, unsaturated fatty acids, and proteins. We incubated human dermal fibroblast cultures for 48 hours with high and low concentrations of CSE extracts and analyzed changes in gene expression. Cells treated with CSE extract showed concentration-dependent upregulation of collagen type I genes and of multiple antioxidative genes, including OXR1, TXNRD1, and PRDX family genes. We further conducted in silico phylogenetic footprinting analysis of promoter regions. These results suggested that transcription factors such as acute myeloid leukemia-1a and cyclic adenosine monophosphate response element-binding protein may be involved in the observed upregulation of antioxidative genes. Our results support the idea that CSEs are strong candidate sources of antioxidant materials and cosmeceutically effective ingredients. C1 [Yoshino, Atsushi; Polouliakh, Natalia; Meguro, Akira; Takeuchi, Masaki; Kawagoe, Tatsukata; Mizuki, Nobuhisa] Yokohama City Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med, Yokohama, Kanagawa, Japan. [Polouliakh, Natalia] Sony Comp Sci Labs Inc, Fundamental Res Labs, Tokyo, Japan. [Polouliakh, Natalia] Syst Biol Inst, Tokyo, Japan. [Takeuchi, Masaki] NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. RP Mizuki, N (reprint author), Yokohama City Univ, Dept Ophthalmol & Visual Sci, Kanazawa Ward, Fukuura 3-9, Yokohama, Kanagawa 2360004, Japan. EM mizunobu@med.yokohama-cu.ac.jp NR 53 TC 0 Z9 0 U1 2 U2 2 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-1998 J9 CLIN INTERV AGING JI Clin. Interv. Aging PY 2016 VL 11 BP 1159 EP 1168 DI 10.2147/CIA.S102092 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA DU5BM UT WOS:000382227000001 PM 27621603 ER PT J AU Hakkinen, P Publicker, S AF Hakkinen, Pertti Publicker, Stephanie TI Bringing the National Library of Medicine Toxicology Tutorials into the 21st Century SO CLINICAL TOXICOLOGY LA English DT Meeting Abstract DE Education; Online; Toxicology C1 [Hakkinen, Pertti; Publicker, Stephanie] NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM pertti.hakkinen@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1556-3650 EI 1556-9519 J9 CLIN TOXICOL JI Clin. Toxicol. PY 2016 VL 54 IS 8 MA 269 BP 783 EP 783 PG 1 WC Toxicology SC Toxicology GA DT2ER UT WOS:000381294100277 ER PT J AU Walitt, B Klose, P Ueceyler, N Phillips, T Hauser, W AF Walitt, Brian Klose, Petra Ueceyler, Nurcan Phillips, Tudor Haeuser, Winfried TI Antipsychotics for fibromyalgia in adults SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; INDIVIDUAL PATIENT DATA; CHRONIC PAIN; ATYPICAL ANTIPSYCHOTICS; TREATMENT OUTCOMES; RESPONDER ANALYSIS; LONGITUDINAL DATA; NEUROPATHIC PAIN; TRIALS; METAANALYSIS AB Background This review is one of a series on drugs used to treat fibromyalgia. Fibromyalgia is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue. It affects approximately 2% of the general population. Up to 70% of patients with fibromyalgia meet the criteria for a depressive or anxiety disorder. People often report high disability levels and poor health-related quality of life. Drug therapy focuses on reducing key symptoms and disability, and improving health-related quality of life. Antipsychotics might reduce fibromyalgia and associated mental health symptoms. Objectives To assess the efficacy, tolerability and safety of antipsychotics in fibromyalgia in adults. Search methods We searched CENTRAL (2016, Issue 4), MEDLINE and EMBASE to 20 May 2016, together with reference lists of retrieved papers and reviews and two clinical trial registries. We also contacted trial authors. Selection criteria We selected controlled trials of at least four weeks duration of any formulation of antipsychotics used for the treatment of fibromyalgia in adults. Data collection and analysis We extracted the data from all included studies and two review authors independently assessed study risks of bias. We resolved discrepancies by discussion. We performed analysis using three tiers of evidence. We derived first tier evidence from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for drop-outs, at least 200 participants in the comparison, eight to 12 weeks duration, parallel design), second tier evidence from data that failed to meet one or more of these criteria and that we considered at some risk of bias but with adequate numbers in the comparison, and third tier evidence from data involving small numbers of participants that we considered very likely to be biased or used outcomes of limited clinical utility, or both. We rated the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Main results We included a total of four studies with 296 participants. Three studies with 206 participants compared quetiapine, an atypical (second-generation) antipsychotic, with placebo. One study used a cross-over design and two studies a parallel-group design. Study duration was eight or 12 weeks. Quetiapine was used in all studies with a bedtime dosage between 50 and 300 mg/day. All studies had one or more sources of potential major bias and we judged them to be at moderate risk of bias overall. The primary outcomes in this review were participant-reported pain relief of 50% or greater, Patient Global Impression of Change (PGIC) much or very much improved, withdrawal due to adverse events (tolerability) and serious adverse events (safety). Second tier evidence indicated that quetiapine was not statistically superior to placebo in the number of participants with a 50% or more pain reduction (very low quality evidence). No study reported data on PGIC. A greater proportion of participants on quetiapine reported a 30% or more pain reduction (risk difference (RD) 0.12, 95% confidence interval (CI) 0.00 to 0.23; number needed to treat for an additional benefit (NNTB) 8, 95% CI 5 to 100) (very low quality evidence). A greater proportion of participants on quetiapine reported a clinically relevant improvement of health-related quality of life compared to placebo (RD 0.18, 95% CI 0.05 to 0.31; NNTB 5, 95% CI 3 to 20) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing sleep problems (standardised mean difference (SMD) -0.67, 95% CI -1.10 to -0.23), depression (SMD -0.39, 95% CI -0.74 to -0.04) and anxiety (SMD -0.40, 95% CI -0.69 to -0.11) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing the risk of withdrawing from the study due to a lack of efficacy (RD -0.14, 95% CI -0.23 to -0.05) (very low quality evidence). There was no statistically significant difference between quetiapine and placebo in the proportion of participants withdrawing due to adverse events (tolerability) (very low quality evidence), in the frequency of serious adverse events (safety) (very low quality evidence) and in the proportion of participants reporting dizziness and somnolence as an adverse event (very low quality evidence). In more participants in the quetiapine group a substantial weight gain was noted (RD 0.08, 95% CI 0.02 to 0.15; number needed to treat for an additional harm (NNTH) 12, 95% CI 6 to 50) (very low quality evidence). We downgraded the quality of evidence by three levels to a very low quality rating because of limitations of study design, indirectness (patients with major medical diseases and mental disorders were excluded) and imprecision (fewer than 400 patients were analysed). One parallel design study with 90 participants compared quetiapine (50 to 300 mg/day flexible at bedtime) to amitriptyline (10 to 75 mg/day flexible at bedtime). The study had three major risks of bias and we judged it to be at moderate risk of bias overall. We downgraded the quality of evidence by two levels to a low quality rating because of indirectness (patients with major medical diseases and mental disorders were excluded) and imprecision (fewer than 400 patients were analysed). Third tier evidence indicated no statistically significant differences between the two drugs. Both drugs did not statistically significantly differ in the reduction of average scores for pain, fatigue, sleep problems, depression, anxiety and for limitations of health-related quality of life and in the proportion of participants reporting dizziness, somnolence and weight gain as a side effect (low quality evidence). Compared to amitriptyline, more participants left the study due to adverse events (low quality evidence). No serious adverse events were reported (low quality evidence). We found no relevant study with other antipsychotics than quetiapine in fibromyalgia. Authors' conclusions Very low quality evidence suggests that quetiapine may be considered for a time-limited trial (4 to 12 weeks) to reduce pain, sleep problems, depression and anxiety in fibromyalgia patients with major depression. Potential side effects such as weight gain should be balanced against the potential benefits in shared decision making with the patient. C1 [Walitt, Brian] NIH, Natl Ctr Complementary & Integrat Hlth, Bldg 10, Bethesda, MD 20892 USA. [Walitt, Brian] NINR, NIH, Bethesda, MD 20892 USA. [Klose, Petra] Univ Duisburg Essen, Fac Med, Kliniken Essen Mitte, Dept Internal & Integrat Med, Essen, Germany. [Ueceyler, Nurcan] Univ Wurzburg, Dept Neurol, Wurzburg, Germany. [Phillips, Tudor] Univ Oxford, Pain Res, Oxford, England. [Phillips, Tudor] Univ Oxford, Nuffield Dept Clin Neurosci, Nuffield Div Anaesthet, Oxford, England. [Haeuser, Winfried] Tech Univ Munich, Dept Psychosomat Med & Psychotherapy, Langerstr 3, D-81675 Munich, Germany. RP Hauser, W (reprint author), Tech Univ Munich, Dept Psychosomat Med & Psychotherapy, Langerstr 3, D-81675 Munich, Germany. EM whaeuser@klinikum-saarbruecken.de OI Uceyler, Nurcan/0000-0001-6973-6428; Klose, Petra/0000-0001-9319-2491 FU Rut und Klaus-Bahlsen-Stiftung, Germany; Rut und Klaus-Bahlsen-Stiftung FX External sourcesr Rut und Klaus-Bahlsen-Stiftung, Germany.r P Klose was supported by the Rut und Klaus-Bahlsen-Stiftung NR 81 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2016 IS 6 AR CD011804 DI 10.1002/14651858.CD011804.pub2 PG 47 WC Medicine, General & Internal SC General & Internal Medicine GA DS9MI UT WOS:000381106800040 PM 27251337 ER PT J AU Du, J Zhu, M Bao, HK Li, B Dong, YL Xiao, CJ Zhang, GY Henter, I Rudorfer, M Vitiello, B AF Du, Jing Zhu, Ming Bao, Hongkun Li, Bai Dong, Yilong Xiao, Chunjie Zhang, Grace Y. Henter, Ioline Rudorfer, Matthew Vitiello, Benedetto TI The Role of Nutrients in Protecting Mitochondrial Function and Neurotransmitter Signaling: Implications for the Treatment of Depression, PTSD, and Suicidal Behaviors SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION LA English DT Review DE Vitamin; oxidative stress; synaptic plasticity; lipid; suicide; zinc ID PLACEBO-CONTROLLED TRIAL; LOW SERUM-CHOLESTEROL; POLYUNSATURATED FATTY-ACIDS; POSTTRAUMATIC-STRESS-DISORDER; PRELIMINARY DOUBLE-BLIND; SEROTONIN REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; OBSTRUCTIVE SLEEP-APNEA; BLOOD-CELL MEMBRANES; OXIDATIVE DNA-DAMAGE AB Numerous studies have linked severe stress to the development of major depressive disorder (MDD) and suicidal behaviors. Furthermore, recent preclinical studies from our laboratory and others have demonstrated that in rodents, chronic stress and the stress hormone cortisol cause oxidative damage to mitochondrial function and membrane lipids in the brain. Mitochondria play a key role in synaptic neurotransmitter signaling by providing adenosine triphosphate (ATP), mediating lipid and protein synthesis, buffering intracellular calcium, and regulating apoptotic and resilience pathways. Membrane lipids are similarly essential to central nervous system (CNS) function because cholesterol, polyunsaturated fatty acids, and sphingolipids form a lipid raft region, a special lipid region on the membrane that mediates neurotransmitter signaling through G-protein-coupled receptors and ion channels. Low serum cholesterol levels, low antioxidant capacity, and abnormal early morning cortisol levels are biomarkers consistently associated with both depression and suicidal behaviors. In this review, we summarize the manner in which nutrients can protect against oxidative damage to mitochondria and lipids in the neuronal circuits associated with cognitive and affective behaviors. These nutrients include 3 fatty acids, antioxidants (vitamin C and zinc), members of the vitamin B family (Vitamin B12 and folic acid), and magnesium. Accumulating data have shown that these nutrients can enhance neurocognitive function, and may have therapeutic benefits for depression and suicidal behaviors. A growing body of studies suggests the intriguing possibility that regular consumption of these nutrients may help prevent the onset of mood disorders and suicidal behaviors in vulnerable individuals, or significantly augment the therapeutic effect of available antidepressants. These findings have important implications for the health of both military and civilian populations. C1 [Du, Jing; Zhu, Ming; Bao, Hongkun; Li, Bai; Dong, Yilong; Xiao, Chunjie] Yunnan Univ, Sch Med, 2 Cuihubeilu, Kunming 650091, Yunnan, Peoples R China. [Rudorfer, Matthew; Vitiello, Benedetto] NIMH, Div Serv & Intervent Res, NIH, Rockville, MD 20857 USA. [Du, Jing; Zhang, Grace Y.] NIMH, Mol Pathophysiol Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Henter, Ioline] NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Du, J (reprint author), Yunnan Univ, Sch Med, 2 Cuihubeilu, Kunming 650091, Yunnan, Peoples R China. EM dujing@ynu.edu.cn FU Yunnan High-level Professional Funding [2012HA004]; National Science Fund for Young Scholars from the Natural Science Foundation of China [31300891]; Intramural Program of the National Institute of Mental Health; National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS) FX The authors gratefully acknowledge the support of the Yunnan High-level Professional Funding (2012HA004), National Science Fund for Young Scholars (31300891) from the Natural Science Foundation of China, and the funding from Intramural Program of the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS). NR 199 TC 2 Z9 2 U1 14 U2 17 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1040-8398 EI 1549-7852 J9 CRIT REV FOOD SCI JI Crit. Rev. Food Sci. Nutr. PY 2016 VL 56 IS 15 BP 2560 EP 2578 DI 10.1080/10408398.2013.876960 PG 19 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA DV2NO UT WOS:000382757500008 PM 25365455 ER PT S AU Quenet, D Sturgill, D Dalal, Y AF Quenet, D. Sturgill, D. Dalal, Y. BE Marmorstein, R TI Identifying Centromeric RNAs Involved in Histone Dynamics In Vivo SO ENZYMES OF EPIGENETICS, PT A SE Methods in Enzymology LA English DT Review; Book Chapter ID HUMAN GENOME; SEQ DATA; DNA; ALIGNMENT; TRANSCRIPTION; SEQUENCES; ENCODE; GENE; SITU AB Over the last decade, the long accepted dogma that heterochromatin is silent has been challenged by increasing evidence of active transcription in these apocryphally annotated quiescent regions of the genome. The recent discovery of noncoding RNAs (ncRNAs) originating from, or localizing to, centromeres, pericentromeres, and telomeres (ie, constitutive heterochromatin) suggest a potential role for ncRNAs in genome integrity. This new paradigm suggests that ncRNAs may recruit chromatin-binding factors, stabilize the higher order folded state of the chromatin fiber, and participate in regulation of processes such as transcription-mediated nucleosome assembly. Thus, identifying, purifying, and elucidating the function of ncRNAs has the potential to provide key insights into genome organization and is currently a topic of intense experimental investigation. C1 [Quenet, D.; Sturgill, D.; Dalal, Y.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Quenet, D.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. RP Quenet, D; Dalal, Y (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.; Quenet, D (reprint author), Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. EM delphine.quenet@med.uvm.edu; dalaly@mail.nih.gov NR 27 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-805432-1; 978-0-12-805365-2 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2016 VL 573 BP 445 EP 466 DI 10.1016/bs.mie.2016.01.010 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BF5MN UT WOS:000382281500021 PM 27372766 ER PT S AU Kanno, Y Witte, S O'Shea, JJ AF Kanno, Yuka Witte, Steven O'Shea, John J. BE Doerfler, W Bohm, P TI Lymphocyte Identity and Genomic Switches SO EPIGENETICS - A DIFFERENT WAY OF LOOKING AT GENETICS SE Epigenetics and Human Health LA English DT Proceedings Paper CT 5th Weissenburg Symposium on Epigenetics - A Different Way of Looking at Genetics CY SEP 14-17, 2014 CL Weissenburg Bayern, GERMANY DE Chromatin; Transcription; Enhancer; Histone; Super-enhancers; Regulome ID MASTER TRANSCRIPTION FACTORS; SUPER-ENHANCERS; GENE-EXPRESSION; CELL IDENTITY; SUSCEPTIBILITY LOCI; HUMAN-DISEASE; RISK LOCI; CHROMATIN; IDENTIFICATION; METAANALYSIS AB Naive CD4+ helper T lymphocytes can adapt to many fates upon encountering environmental stimuli and differentiate into a spectrum of effector or regulatory lineages. In the early days, immunologists defined their functionality by expression of a small handful of signature genes. With the present extraordinary capabilities to gain genome-wide information on gene transcription, chromatin state, and transcription factor recruitment, we now come to appreciate the importance of a vast majority of genomic region outside of annotated genes. This is where many regulatory elements including enhancers exist, serving as a platform for transcription factors and operating as switches for genes in proximity and at a distance. Regions of strong and extensive deposition of enhancer marks represent super-enhancers (SEs). Distinctive super-enhancer structure associates with key genes that define cell phenotype as well as highly sensitive drug targets. Accumulating evidence on chromatin state indicates that cell identity is established by converging sequential actions of pioneer transcription factors, signal-dependent transcription factors, and lineage-defining master transcription factors. Chromatin state integrates past and current action of transcription factors and presents it as epigenetic fingerprints. Deciphering fine genomic fingerprints and identifying genomic switches will pave the way for deeper understanding of identity, plasticity, and functionality of cell lineages. C1 [Kanno, Yuka; Witte, Steven; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Kanno, Y (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. EM kannoy@mail.nih.gov NR 41 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2191-2262 BN 978-3-319-27186-6; 978-3-319-27184-2 J9 EPIGENETICS HUM HLTH PY 2016 BP 41 EP 52 DI 10.1007/978-3-319-27186-6_3 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA BF4XE UT WOS:000381755800003 ER PT J AU Lopez, E Thompson, R Gainotti, S Wang, CM Rubinstein, Y Taruscio, D Monaco, L Lochmuller, H Alonso, V de la Paz, MP AF Lopez, Estrella Thompson, Rachel Gainotti, Sabina Wang, Chiuhui Mary Rubinstein, Yaffa Taruscio, Domenica Monaco, Lucia Lochmueller, Hanns Alonso, Veronica Posada de la Paz, Manuel TI Overview of existing initiatives to develop and improve access and data sharing in rare disease registries and biobanks worldwide SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Review DE Interoperability; data sharing; patient registries; biobanks; standardization; international collaboration ID GENETIC-DISEASES; RD-CONNECT; PLATFORM; CARE; BIOREPOSITORY; MATCHMAKING; DISORDERS; CENTERS; NETWORK; EUROPE AB Introduction: There are currently several strategies developed to facilitate access and data sharing in the rare disease field. These strategies have paid special attention to the importance of rare disease patient registries and biobanks, as they are essential tools for surveillance and the provision of biosamples and phenotypic and genetic data for research worldwide. However, they are usually fragmented by disease, data model and country. Moreover, these resources have restricted access in order to protect privacy of patient data. Areas covered: This article is an overview of existing initiatives that facilitate access to rare disease patient registries and biobanks, future challenges of accessing data/biosamples and the major barriers to achieve interoperability and worldwide sharing. Expert opinion: RD patient registries and biobanks play an important role in the discovery of either new rare diseases or new phenotype-genotype correlations. However, there is still little access to data and important limitations regarding interoperability between these resources. The improvement of access and data sharing among patient registries and biobanks worldwide, together with the establishment of harmonized regulatory criteria, might enhance knowledge on rare diseases and the discovery of new diagnostic and therapeutic procedures. C1 [Lopez, Estrella] Inst Hlth Carlos III ISCIII, Inst Rare Dis Res IIER, Madrid, Spain. [Thompson, Rachel; Lochmueller, Hanns] Newcastle Univ, Inst Med Genet, John Walton Muscular Dystrophy Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England. [Gainotti, Sabina; Taruscio, Domenica] Ist Super Sanita, Natl Ctr Rare Dis, Rome, Italy. [Wang, Chiuhui Mary; Monaco, Lucia] Fdn Telethon, Milan, Italy. [Rubinstein, Yaffa] NIH, ORDR, NCATS, Bldg 10, Bethesda, MD 20892 USA. [Alonso, Veronica; Posada de la Paz, Manuel] Inst Hlth Carlos III ISCIII, SpainRDR, Inst Rare Dis Res IIER, Madrid, Spain. [Alonso, Veronica; Posada de la Paz, Manuel] Inst Hlth Carlos III ISCIII, CIBERER, Madrid, Spain. RP Lopez, E (reprint author), Inst Hlth Carlos III, Inst Rare Dis Res, Avda Monforte de Lemos 5, Madrid 28029, Spain. EM elopez@isciii.es OI gainotti, sabina/0000-0002-6006-9064; Wang, Chiuhui Mary/0000-0003-1163-0959 FU European Union [305444, FP7/0017-2013] FX This work has been funded by the European Union Seventh Framework Program (FP7/0017-2013) under grant number 305444 'RD-Connect: An integrated platform connecting registries, biobanks and clinical bioinformatics for rare disease research'. 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 48 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PY 2016 VL 4 IS 7 BP 729 EP 739 DI 10.1080/21678707.2016.1188002 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DU4HH UT WOS:000382173000007 ER PT J AU Theeler, BJ Gilbert, MR AF Theeler, Brett J. Gilbert, Mark R. TI Investigating therapies in ependymoma SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Review DE Ependymoma; anaplastic ependymoma; myxopapillary ependymoma; targeted therapy; immunotherapy ID ANDERSON-CANCER-CENTER; CENTRAL-NERVOUS-SYSTEM; RECURRENT INTRACRANIAL EPENDYMOMAS; POSTERIOR-FOSSA EPENDYMOMAS; PROGRESSION-FREE SURVIVAL; PROGNOSTIC-FACTORS; ADULT PATIENTS; MYXOPAPILLARY EPENDYMOMA; RADIATION-THERAPY; CLINICAL ARTICLE AB Introduction: Ependymomas are a heterogeneous group of primary central nervous system neoplasms with varied clinical characteristics, pathologic appearances, survival outcomes, cytogenetic, gene expression, and epigenetic profiles. The variable outcomes with adjuvant radiotherapy and the meager success of cytotoxic chemotherapies point to a need to develop personalized, targeted therapies. Areas covered: This review provides an overview of clinical, pathologic, radiographic, prognostic, and treatment characteristics of ependymomas, summarizes recent discoveries in gene expression profiling, and future directions for the development of targeted and immunologic therapeutic strategies. Expert opinion: Translating the quickly accumulating molecular data into an improved system of grading, classification, prognostication, and therapeutic development will be necessary to improve patient outcomes. C1 [Theeler, Brett J.] Walter Reed Natl Mil Med Ctr, Dept Neurol, Neurol, 8901 Wisconsin Ave Bldg 19,6th Floor, Bethesda, MD 20889 USA. [Theeler, Brett J.] John P Murtha Canc Ctr, 8901 Wisconsin Ave Bldg 19,6th Floor, Bethesda, MD 20889 USA. [Gilbert, Mark R.] NIH, Neurooncol Branch, Bldg 10, Bethesda, MD 20892 USA. RP Theeler, BJ (reprint author), Walter Reed Natl Mil Med Ctr, Dept Neurol, Neurol, 8901 Wisconsin Ave Bldg 19,6th Floor, Bethesda, MD 20889 USA.; Theeler, BJ (reprint author), John P Murtha Canc Ctr, 8901 Wisconsin Ave Bldg 19,6th Floor, Bethesda, MD 20889 USA. EM brett.j.theeler.mil@mail.mil NR 103 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PY 2016 VL 4 IS 7 BP 761 EP 773 DI 10.1080/21678707.2016.1191347 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DU4HH UT WOS:000382173000010 ER PT J AU Thomas, A AF Thomas, Anish TI Should anti-mesothelin therapies be explored in lung cancer? SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Editorial Material DE Mesothelin; NSCLC; lung adenocarcinoma; antibody-drug conjugate; immunotoxin ID OVARIAN CANCERS; EXPRESSION; TUMORS; ADENOCARCINOMA; SURVIVAL; TARGET C1 [Thomas, Anish] NCI, Thorac & GI Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Thomas, A (reprint author), NCI, Thorac & GI Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM anish.thomas@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 18 TC 0 Z9 0 U1 3 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1473-7140 EI 1744-8328 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PY 2016 VL 16 IS 7 BP 677 EP 679 DI 10.1080/14737140.2016.1192472 PG 3 WC Oncology SC Oncology GA DU6KB UT WOS:000382322400002 PM 27210575 ER PT J AU Miura, K AF Miura, Kazutoyo TI Progress and prospects for blood-stage malaria vaccines SO EXPERT REVIEW OF VACCINES LA English DT Review DE Malaria; Plasmodium falciparum; blood-stage; vaccine; in vitro assays; challenge models; clinical trial ID PLASMODIUM-FALCIPARUM MALARIA; APICAL MEMBRANE ANTIGEN-1; MEROZOITE SURFACE PROTEIN-1; INHIBIT PARASITE GROWTH; NATURALLY ACQUIRED ANTIBODIES; ERYTHROCYTE-BINDING PROTEIN; MONTANIDE ISA 720; IN-VITRO; INFECTED ERYTHROCYTES; IMMUNOGENICITY TRIAL AB There have been significant decreases in malaria mortality and morbidity in the last 10-15 years, and the most advanced pre-erythrocytic malaria vaccine, RTS,S, received a positive opinion from European regulators in July 2015. However, no blood-stage vaccine has reached a phase III trial. The first part of this review summarizes the pros and cons of various assays and models that have been and will be used to predict the efficacy of blood-stage vaccines. In the second part, blood-stage vaccine candidates that showed some efficacy in human clinical trials or controlled human malaria infection models are discussed. Then, candidates under clinical investigation are described in the third part, and other novel candidates and strategies are reviewed in the last part. C1 [Miura, Kazutoyo] NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. RP Miura, K (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM kmiura@niaid.nih.gov FU Intramural Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 162 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1476-0584 EI 1744-8395 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PY 2016 VL 15 IS 6 BP 765 EP 781 DI 10.1586/14760584.2016.1141680 PG 17 WC Immunology SC Immunology GA DV2TF UT WOS:000382773600010 PM 26760062 ER PT J AU Strauss, J Madan, RA AF Strauss, Julius Madan, Ravi A. TI Therapeutic vaccines for prostate cancer: recent advances and future directions SO EXPERT REVIEW OF VACCINES LA English DT Review DE Prostate Cancer; Vaccines; Immunotherapy ID SITU GENE-THERAPY; ANDROGEN-DEPRIVATION THERAPY; CELL-BASED IMMUNOTHERAPY; CYTOTOXIC T-LYMPHOCYTES; DOSE-ESCALATION TRIAL; TUMOR-CELLS; UNTREATED MELANOMA; SIPULEUCEL-T; PHASE-II; COMBINATION THERAPY AB In recent years, therapeutic cancer vaccines have emerged as a viable and promising treatment for prostate cancer. Beyond sipuleucel-T, phase III trials are evaluating multiple vaccine platforms in men with this disease. Growing data evaluating vaccine therapies suggests that these agents are more effective in patients with more indolent and possibly also earlier stages of disease. In addition, a wealth of preclinical data has shown that traditional prostate cancer treatments including anti androgens, cytotoxic and radiation therapies may provide immunologic synergy when given in combination with vaccine platforms. Building off this data, numerous clinical trials are evaluating therapeutic cancer vaccines in early stage prostate cancer and also in combination with traditional prostate cancer therapies. In addition, in order to optimize immune responses, ongoing trials are evaluating vaccines in combination with immune checkpoint inhibitors. Preliminary data from these trials have been promising and are offering an exciting glimpse at the future of immunotherapy for this disease. C1 [Strauss, Julius; Madan, Ravi A.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Madan, RA (reprint author), NCI, Genitourinary Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM madanr@mail.nih.gov NR 67 TC 1 Z9 1 U1 2 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1476-0584 EI 1744-8395 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PY 2016 VL 15 IS 7 BP 907 EP 914 DI 10.1586/14760584.2016.1155988 PG 8 WC Immunology SC Immunology GA DV2TK UT WOS:000382774100012 PM 26889831 ER PT J AU Hall, AJ Glass, RI Parashar, UD AF Hall, Aron J. Glass, Roger I. Parashar, Umesh D. TI New insights into the global burden of noroviruses and opportunities for prevention SO EXPERT REVIEW OF VACCINES LA English DT Editorial Material DE Norovirus; gastroenteritis; diarrhea; disease burden; global health; vaccine ID UNITED-STATES; DEVELOPING-COUNTRIES; GASTROENTERITIS; DISEASE; OUTBREAKS; IMMUNITY; CHILDREN C1 [Hall, Aron J.; Parashar, Umesh D.] Ctr Dis Control & Prevent, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. [Glass, Roger I.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. RP Hall, AJ (reprint author), Ctr Dis Control & Prevent, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. EM ajhall@cdc.gov NR 20 TC 1 Z9 1 U1 3 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1476-0584 EI 1744-8395 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PY 2016 VL 15 IS 8 BP 949 EP 951 DI 10.1080/14760584.2016.1178069 PG 3 WC Immunology SC Immunology GA DV2TR UT WOS:000382774900001 PM 27142965 ER PT J AU Musich, T Robert-Guroff, M AF Musich, Thomas Robert-Guroff, Marjorie TI New developments in an old strategy: heterologous vector primes and envelope protein boosts in HIV vaccine design SO EXPERT REVIEW OF VACCINES LA English DT Review DE Vector prime/envelope boost vaccine strategy; DNA; adenovirus; poxvirus vectors; monomeric/trimeric envelope immunogens; neutralizing/non-neutralizing antibody; cellular immunity ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMORAL IMMUNE-RESPONSES; T-CELL RESPONSES; NEUTRALIZING ANTIBODY-RESPONSES; HIGHLY PATHOGENIC SIV; RHESUS MACAQUES; DNA VACCINE; IN-VIVO; NONHUMAN-PRIMATES; ADENOVIRUS VACCINES AB Prime/boost vaccination strategies for HIV/SIV vaccine development have been used since the early 1990s and have become an established method for eliciting cell and antibody mediated immunity. Here we focus on induction of protective antibodies, both broadly neutralizing and non-neutralizing, with the viral envelope being the key target antigen. Prime/boost approaches are complicated by the diversity of autologous and heterologous priming vectors, and by various forms of envelope booster immunogens, many still in development as structural studies aim to design stable constructs with exposure of critical epitopes for protective antibody elicitation. This review discusses individual vaccine components, reviews recent prime/boost strategies and their outcomes, and highlights complicating factors arising as greater knowledge concerning induction of adaptive, protective immunity is acquired. C1 [Musich, Thomas; Robert-Guroff, Marjorie] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Robert-Guroff, M (reprint author), NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM guroffm@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute FX The authors were supported by the Intramural Research Program of the NIH, National Cancer Institute. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. NR 165 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1476-0584 EI 1744-8395 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PY 2016 VL 15 IS 8 BP 1015 EP 1027 DI 10.1586/14760584.2016.1158108 PG 13 WC Immunology SC Immunology GA DV2TR UT WOS:000382774900008 PM 26910195 ER PT J AU Riddler, SA Husnik, M Gorbach, PM Levy, L Parikh, U Livant, E Pather, A Makanani, B Muhlanga, F Kasaro, M Martinson, F Elharrar, V Balkuson, JE AF Riddler, Sharon A. Husnik, Marla Gorbach, Pamina M. Levy, Lisa Parikh, Urvi Livant, Edward Pather, Arendevi Makanani, Bonus Muhlanga, Felix Kasaro, Margaret Martinson, Francis Elharrar, Vanessa Balkuson, Jennifer E. CA MTN-015 Protocol Team Microbicide TI Long-term follow-up of HIV seroconverters in microbicide trials - rationale, study design, and challenges in MTN-015 SO HIV CLINICAL TRIALS LA English DT Article DE HIV; clinical trial design; cohort Study; prevention; microbicides; pre-exposure prophylaxis; seroconversion; drug resistance ID PREEXPOSURE PROPHYLAXIS TRIAL; DISEASE PROGRESSION; DRUG-RESISTANCE; WOMEN; PREVENTION; INFECTION; GEL; TANZANIA AB Background: As the effect of biomedical prevention interventions on the natural history of HIV-1 infection in participants who seroconvert is unknown, the Microbicide Trials Network (MTN) established a longitudinal study (MTN-015) to monitor virologic, immunological, and clinical outcomes, as well as behavioral changes among women who become HIV-infected during MTN trials. We describe the rationale, study design, implementation, and enrollment of the initial group of participants in the MTN seroconverter cohort. Methods: Initiated in 2008, MTN-015 is an ongoing observational cohort study enrolling participants who acquire HIV-1 infection during effectiveness studies of candidate microbicides. Eligible participants from recently completed and ongoing MTN trials are enrolled after seroconversion and return for regular follow-up visits with clinical and behavioral data collection. Biologic samples including blood and genital fluids are stored for future testing. Results: MTN-015 was implemented initially at six African sites and enrolled 100/139 (72%) of eligible women who seroconverted in HIV Prevention Trials Network protocol 035 (HPTN 035, conducted by the MTN). The median time from seroconversion in HPTN 035 to enrollment in MTN-015 was 18 months. Retention was good with >70% of visits completed. Implementation challenges included regulatory reviews, translation, and testing of questionnaires, and site readiness. Conclusions: Enrollment of HIV-seroconverters into a longitudinal observational follow-up study is feasible and acceptable to participants. Data and samples collected in this protocol will be used to assess safety of investigational HIV microbicides and answer other important public health questions for HIV infected women. C1 [Riddler, Sharon A.; Parikh, Urvi] Univ Pittsburgh, Div Infect Dis, Keystone Bldg,Suite 510,3520 Fifth Ave, Pittsburgh, PA 15213 USA. [Husnik, Marla; Balkuson, Jennifer E.] Fred Hutchinson Canc Res Ctr, MTN Stat & Data Management Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Gorbach, Pamina M.] Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA USA. [Levy, Lisa] FHI360, Durham, NC USA. [Livant, Edward] Magee Womens Res Inst, Microbicide Trials Network, Pittsburgh, PA USA. [Pather, Arendevi] South African Med Res Council, HIV Prevent Res Unit, Durban, South Africa. [Makanani, Bonus] Queen Elizabeth Cent Hosp, Coll Med John Hopkins Univ Res Project, Blantyre, Malawi. [Muhlanga, Felix] Univ Zimbabwe, UZ UCSF Collaborat Res Programme, Harare, Zimbabwe. [Kasaro, Margaret] Ctr Infect Dis Res Zambia, Lusaka, Zambia. [Martinson, Francis] Kamuzu Cent Hosp, UNC Project Tidziwe Ctr, Lilongwe, Malawi. [Elharrar, Vanessa] NIH, Div Aids, Bldg 10, Bethesda, MD 20892 USA. RP Riddler, SA (reprint author), Univ Pittsburgh, Div Infect Dis, Keystone Bldg,Suite 510,3520 Fifth Ave, Pittsburgh, PA 15213 USA. EM riddler@pitt.edu FU National Institute of Allergy and Infectious Diseases [UM1AI068633, UM1AI068615, UM1AI106707]; Eunice Kennedy Shriver National Institute of Child Health U.S. National Institutes of Health; Human Development U.S. National Institutes of Health; National Institute of Mental Health U.S. National Institutes of Health FX The Microbicide Trials Network is funded by the National Institute of Allergy and Infectious Diseases [grant number UM1AI068633], [grant number UM1AI068615], [grant number UM1AI106707], with co-funding from the Eunice Kennedy Shriver National Institute of Child Health; Human Development and the National Institute of Mental Health, all components of the U.S. 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. NR 22 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1528-4336 EI 1945-5771 J9 HIV CLIN TRIALS JI HIV Clin. Trials PY 2016 VL 17 IS 5 BP 204 EP 211 DI 10.1080/15284336.2016.1212561 PG 8 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA DU6FJ UT WOS:000382309300005 PM 27465646 ER PT J AU Chiralaksanakul, A AF Chiralaksanakul, Anukal TI Impact of bias in the estimation of American-style options by Monte Carlo simulation SO JOURNAL OF MODELLING IN MANAGEMENT LA English DT Article DE Simulation; Estimation; Bias approximation; Monte Carlo methods; Option valuation ID STOCHASTIC PROGRAMS; VARIANCE AB Purpose - The purpose of this paper is to investigate the impact of bias error resulted from using Monte Carlo simulation in evaluating the American-style option value. Design/methodology/approach - The authors develop an analytical approximation formula to quantify the bias error under the assumption of conditionally independent and identically distributed samples of asset prices. The bias arises from the nested optimization and expectation calculation. The formula is then used to numerically quantify the bias and as an objective function for bias minimization for a given budget of samples. Findings - Monte Carlo methods used in valuation of American-style options can results in bias error ranging from 2 to 10 per cent of the option value. The bias error can be reduced up to 50 per cent either by performing a better scheme for sampling or by efficiently allocating sample size. Research limitations/implications - The running time of the proposed procedure can be improved by using a specialized algorithm to solve the sample size allocation problem instead of using a commercially available subroutine MINOS. Other sampling procedures for bias reduction may be extended and applied to this multi-stage problem. Practical implications - The methodology can help to more accurately approximate the option value. Originality/value - The paper provides a method to develop an analytical approximation for bias error and provide a numerical experiment to test the methodology. C1 [Chiralaksanakul, Anukal] NIDA, Sch Business Adm, Bangkok, Thailand. RP Chiralaksanakul, A (reprint author), NIDA, Sch Business Adm, Bangkok, Thailand. EM anukal@nida.ac.th NR 19 TC 0 Z9 0 U1 2 U2 2 PU EMERALD GROUP PUBLISHING LTD PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY BD16 1WA, W YORKSHIRE, ENGLAND SN 1746-5664 EI 1746-5672 J9 J MODEL MANAG JI J. Model. Manag. PY 2016 VL 11 IS 2 BP 644 EP 659 DI 10.1108/JM2-05-2014-0044 PG 16 WC Management SC Business & Economics GA DT4HC UT WOS:000381439800013 ER PT J AU Zujewski, JA AF Zujewski, Jo Anne TI Changing Paradigms in Breast Cancer Therapeutics: An Extended Abstract SO MEDICAL PRINCIPLES AND PRACTICE LA English DT Article; Proceedings Paper CT 5th Kuwait International Pharmacy Conference (KIPC) CY FEB 01-03, 2015 CL Kuwait, U ARAB EMIRATES SP Kuwait Univ, Kuwait Fdn Advancement Sci, Adv Technol Co, Kuwait Saudi Pharmaceut Ind Co, Kuwait Pharmacists Assoc, Bristol Myers Squibb, Roche Hamad Saleh Al Homaizi Gransons Pharma Co ID PLUS ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; POSTMENOPAUSAL WOMEN; TAMOXIFEN THERAPY; FOLLOW-UP; TRASTUZUMAB; EXEMESTANE; LETROZOLE C1 [Zujewski, Jo Anne] NCI, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. RP Zujewski, JA (reprint author), NCI, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM zujewskj@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 16 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-7571 EI 1423-0151 J9 MED PRIN PRACT JI Med. Princ. Pract. PY 2016 VL 25 SU 2 BP 73 EP 75 DI 10.1159/000443502 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DV2HZ UT WOS:000382742700008 PM 26690956 ER PT J AU Kastrin, A Rindflesch, TC Hristovski, D AF Kastrin, Andrej Rindflesch, Thomas C. Hristovski, Dimitar TI Link Prediction on a Network of Co-occurring MeSH Terms: Towards Literature-based Discovery SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE Complex networks; network analysis; link prediction; literature-based discovery ID FISH-OIL; COMPLEX NETWORKS; SEMANTIC PREDICATIONS; TEXT; SCHIZOPHRENIA; KNOWLEDGE; MEDLINE; CLASSIFIERS; IDENTIFY; RAYNAUDS AB Objectives: Literature-based discovery (LBD) is a text mining methodology for automatically generating research hypotheses from existing knowledge. We mimic the process of LBD as a classification problem on a graph of MeSH terms. We employ unsupervised and supervised link prediction methods for predicting previously unknown connections between biomedical concepts. Methods: We evaluate the effectiveness of link prediction through a series of experiments using a MeSH network that contains the history of link formation between biomedical concepts. We performed link prediction using proximity measures, such as common neighbor (CN), Jaccard coefficient (JC), Adamic/Adar index (AA) and preferential attachment (PA). Our approach relies on the assumption that similar nodes are more likely to establish a link in the future. Results: Applying an unsupervised approach, the AA measure achieved the best performance in terms of area under the ROC curve (AUC = 0.76), followed by CN, JC, and PA. In a supervised approach, we evaluate whether proximity measures can be combined to define a model of link formation across all four predictors. We applied various classifiers, including decision trees, k-nearest neighbors, logistic regression, multilayer perceptron, naive Bayes, and random forests. Random forest classifier accomplishes the best performance (AUC = 0.87). Conclusions: The link prediction approach proved to be effective for LBD processing. Supervised statistical learning approaches clearly outperform an unsupervised approach to link prediction. C1 [Kastrin, Andrej] Fac Informat Studies, Ljubljanska Cesta 31A, SI-8000 Novo Mesto, Slovenia. [Rindflesch, Thomas C.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. [Hristovski, Dimitar] Univ Ljubljana, Fac Med, Inst Biostat & Med Informat, Ljubljana, Slovenia. RP Kastrin, A (reprint author), Fac Informat Studies, Ljubljanska Cesta 31A, SI-8000 Novo Mesto, Slovenia. EM andrej.kastrin@guest.arnes.si FU Slovenian Research Agency; Intramural Research Program of the U.S. National Institutes of Health, National Library of Medicine FX This work was supported in part by the Slovenian Research Agency and by the Intramural Research Program of the U.S. National Institutes of Health, National Library of Medicine. NR 53 TC 1 Z9 1 U1 7 U2 8 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2016 VL 55 IS 4 BP 340 EP 346 DI 10.3414/ME15-01-0108 PG 7 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA DT4JS UT WOS:000381446600008 PM 27435341 ER PT J AU Lee, WS Erdelyi, K Matyas, C Mukhopadhyay, P Varga, ZV Liaudet, L Hasko, G Cihakova, D Mechoulam, R Pacher, P AF Lee, Wen-Shin Erdelyi, Katalin Matyas, Csaba Mukhopadhyay, Partha Varga, Zoltan V. Liaudet, Lucas Hasko, Gyorgy Cihakova, Daniela Mechoulam, Raphael Pacher, Pal TI Cannabidiol Limits T Cell-Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation SO MOLECULAR MEDICINE LA English DT Article ID HUMAN HEART-FAILURE; INTERNATIONAL SOCIETY; OXIDATIVE STRESS; UP-REGULATION; NITRIC-OXIDE; RATS; FIBROSIS; DISEASE; DEATH; MICE AB Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a nonpsychoactive constituent of marijuana that exerts antiinflammatory effects independent of classical cannabinoid receptors. Recently, 80 clinical trials have investigated the effects of CBD in various diseases from inflammatory bowel disease to graft versus host disease. CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received U.S. Food and Drug Administration approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme. Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell-mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD. EAM was characterized by marked myocardial T-cell infiltration, profound inflammatory response and fibrosis (measured by quantitative real-time polymerase chain reaction, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with a pressure-volume conductance catheter-technique. Chronic treatment with CBD largely attenuated the CD3(+) and CD4(+) T cell-mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice. In conclusion, CBD may represent a promising novel treatment for managing-autoimmune myocarditis and possibly other autoimmune disorders and organ transplantation. C1 [Lee, Wen-Shin; Erdelyi, Katalin; Matyas, Csaba; Mukhopadhyay, Partha; Varga, Zoltan V.; Pacher, Pal] NIAAA, Lab Cardiovasc Physiol & Tissue Injury, NIH, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA. [Lee, Wen-Shin] Natl Yang Ming Univ, Sch Med, Taipei Vet Gen Hosp, Div Gen Med,Dept Med, Taipei, Taiwan. [Matyas, Csaba] Semmelweis Univ, Heart & Vasc Ctr, Budapest, Hungary. [Liaudet, Lucas] Univ Hosp Med Ctr, Dept Intens Care Med, Lausanne, Switzerland. [Hasko, Gyorgy] Rutgers New Jersey Med Sch, Dept Surg, Newark, NJ USA. [Cihakova, Daniela] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Cihakova, Daniela] Johns Hopkins Univ, Sch Med, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Cihakova, Daniela] Johns Hopkins Univ, Sch Publ Hlth, Dept Pathol, Baltimore, MD USA. [Cihakova, Daniela] Johns Hopkins Univ, Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Mechoulam, Raphael] Hebrew Univ Jerusalem, Fac Med, Dept Med Chem & Nat Prod, Jerusalem, Israel. RP Pacher, P (reprint author), NIAAA, Lab Cardiovasc Physiol & Tissue Injury, NIH, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Cihakova, Daniela /A-9821-2017; Matyas, Csaba/K-6053-2016; Liaudet, Lucas/E-1322-2017 OI Cihakova, Daniela /0000-0002-8713-2860; Matyas, Csaba/0000-0001-6095-7611; Liaudet, Lucas/0000-0003-2670-4930 FU Intramural Research Program of NIAAA/NIH; Hungarian-American Enterprise Scholarship Fund/Council on International Educational Exchange; Rosztoczy Foundation FX This work was supported by the Intramural Research Program of NIAAA/NIH to P Pacher and by the scholarship of the Hungarian-American Enterprise Scholarship Fund/Council on International Educational Exchange to C Matyas. ZV Varga was supported by the Rosztoczy Foundation. The authors are grateful to George Kunos, the Scientific Director of NIAAA, for continuous support. NR 51 TC 0 Z9 0 U1 7 U2 7 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 EI 1528-3658 J9 MOL MED JI Mol. Med. PY 2016 VL 22 BP 136 EP 146 DI 10.2119/molmed.2016.00007 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DT5KY UT WOS:000381523300001 ER PT S AU Levy, ER Carlsten, M Childs, RW AF Levy, Emily R. Carlsten, Mattias Childs, Richard W. BE Somanchi, SS TI mRNA Transfection to Improve NK Cell Homing to Tumors SO NATURAL KILLER CELLS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Natural killer cells; Cellular immunotherapy; Lymph node homing; Electroporation; Chemotaxis ID NATURAL-KILLER-CELLS; IMMUNOTHERAPY; MANIPULATION; CANCER AB The ability of natural killer (NK) cells to mediate antitumor effects following adoptive transfer is dependent on their capacity to traffic to the microenvironment where tumors reside. Recent studies have shown that cytokine-activated and ex vivo-expanded NK cells lack or express at low levels homing receptors required to achieve tissue-specific tumor targeting by cells administered intravenously. In this chapter, we describe a method to enhance NK cell homing toward specific chemoattractants expressed in secondary lymphoid tissues through genetic modification of NK cells using mRNA electroporation. The method described here is scalable, cGMP-compliant, and offers a strategy to bolster the efficacy of adoptive NK cell immunotherapy for the treatment of hematological malignancies in the clinic. C1 [Levy, Emily R.; Carlsten, Mattias; Childs, Richard W.] NHLBI, Lab Transplantat Immunotherapy, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Levy, Emily R.] George Washington Univ, Inst Biomed Sci, Washington, DC 20052 USA. RP Levy, ER (reprint author), NHLBI, Lab Transplantat Immunotherapy, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.; Levy, ER (reprint author), George Washington Univ, Inst Biomed Sci, Washington, DC 20052 USA. OI Carlsten, Mattias/0000-0001-9815-0012 NR 10 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3684-7; 978-1-4939-3682-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1441 BP 231 EP 240 DI 10.1007/978-1-4939-3684-7_19 D2 10.1007/978-1-4939-3684-7 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA BF4YK UT WOS:000381767300020 PM 27177670 ER PT S AU Angelousi, A Zilbermint, M Berthon, A Espiard, S Stratakis, CA AF Angelousi, Anna Zilbermint, Mihail Berthon, Annabel Espiard, Stephanie Stratakis, Constantine A. BE Pichert, G Jacobs, C TI Diagnosis and Management of Hereditary Adrenal Cancer SO RARE HEREDITARY CANCERS: DIAGNOSIS AND MANAGEMENT SE Recent Results in Cancer Research LA English DT Article; Book Chapter DE Protein Kinase A (PKA); PRKAR1A gene; Li-Fraumeni syndrome; TP53 gene; Familial polyposis; APC gene ID BECKWITH-WIEDEMANN-SYNDROME; LI-FRAUMENI-SYNDROME; ENDOCRINE NEOPLASIA TYPE-1; CLINICAL-PRACTICE GUIDELINES; SOMATIC TP53 MUTATIONS; OF-THE-LITERATURE; CARNEY COMPLEX; ADRENOCORTICAL CARCINOMA; GERMLINE MUTATIONS; P53 MUTATIONS AB Benign adrenocortical tumours (ACT) are relatively frequent lesions; on the contrary, adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with unfavourable prognosis. Recent advances in the molecular understanding of adrenal cancer offer promise for better therapies in the future. Many of these advances stem from the molecular elucidation of genetic conditions predisposing to the development of ACC. Six main clinical syndromes have been described to be associated with hereditary adrenal cancer. In these conditions, genetic counselling plays an important role for the early detection and follow-up of the C1 [Angelousi, Anna; Zilbermint, Mihail; Berthon, Annabel; Espiard, Stephanie; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. RP Angelousi, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. EM a.angelousi@gmail.com; mihail.zilbermint@nih.gov; annabel.berthon@nih.gov; stephanie.espiard@live.fr; stratakc@mail.nih.gov NR 74 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 978-3-319-29998-3; 978-3-319-29996-9 J9 RECENT RESULTS CANC JI Rec. Res. Camcer Res. PY 2016 VL 205 BP 125 EP 147 DI 10.1007/978-3-319-29998-3_8 D2 10.1007/978-3-319-29998-3 PG 23 WC Oncology SC Oncology GA BF5XJ UT WOS:000382769700009 PM 27075352 ER PT J AU Hagman, BT AF Hagman, Brett T. TI Performance of the AUDIT in Detecting DSM-5 Alcohol Use Disorders in College Students SO SUBSTANCE USE & MISUSE LA English DT Article DE Alcohol; college students; AUD criteria; DSM-5; alcohol screening instrument ID IDENTIFICATION TEST AUDIT; SUBSTANCE USE DISORDERS; AT-RISK DRINKING; YOUNG-ADULTS; PRIMARY-CARE; CONTINUUM; CLASSIFICATION; INSTRUMENT; SCREEN AB Background: It is critical that our alcohol screening instruments maintain their accuracy at detecting DSM-5 Alcohol Use Disorder (AUD) symptomatology. The Alcohol Use Disorders Identification Test (AUDIT) is one of the most widely used alcohol screening instruments, despite no studies evaluating its performance for detecting DSM-5 AUDs. Objectives: The present study evaluated the performance of the AUDIT in the screening of DSM-5 AUDs in non-treatment seeking college students. Methods: Participants (N = 251) were undergraduate students who had at least one binge drinking occasion in the past 90-days. Results: The AUROC value for DSM-5 AUD status in the overall sample was.779 (SE =.029; 95% CIs =.721 to.837). The AUROC values for the reference groups of any DSM-IV AUD and any binge drinker were.798 (SE =.028; 95% CIs =.742 to.853) and.827 (SE =.03; 95% CIs.768 -.886), respectively. A similar pattern of findings emerged between males and females. Gender differences emerged in the identification of AUDIT cut-off scores. A score of 8 and 9 had the best balance of sensitivity and specificity for females and males in college, respectively. Conclusion: Findings indicate that the AUDIT has a reasonable degree of diagnostic proficiency in screening for DSM-5 AUDs in college students. C1 [Hagman, Brett T.] NIAAA, Div Treatment & Recovery Res, 2635 Fishers Lane, Washington, DC 20024 USA. RP Hagman, BT (reprint author), NIAAA, Div Treatment & Recovery Res, 2635 Fishers Lane, Washington, DC 20024 USA. EM brett.hagman@nih.gov NR 35 TC 0 Z9 0 U1 7 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6084 EI 1532-2491 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2016 VL 51 IS 11 BP 1521 EP 1528 DI 10.1080/10826084.2016.1188949 PG 8 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA DU6LF UT WOS:000382325500014 PM 27438676 ER PT J AU Conway, KP McGrain, P AF Conway, Kevin P. McGrain, Patrick TI Understanding Substance Use and Addiction Through the Lyrics of Black Sabbath: A Content Analysis SO SUBSTANCE USE & MISUSE LA English DT Article DE Content analysis; longitudinal; addiction; music; drug use ID POPULAR-MUSIC; DRUG-ADDICTION; ALCOHOL-USE; FOLLOW-UP; TOBACCO; PREVALENCE; VIDEOS; ABUSE; RAP; TRENDS AB Background: Heavy metal music is distinguished for its deep sound and lyrical fixation with dark themes including war, destruction, doom, and misery. Such subjects permeate the music of Black Sabbath, the band generally considered the pioneers of heavy metal. One theme-substance use-is recurrent in Black Sabbath's songs and personal lives of its members. Objective/Methods: This study explored the band's relationship with substance use though a content analysis of all songs containing lyrics written and recorded in studio by Black Sabbath. The analysis included 156 songs across 19 albums recorded from 1970 to 2013. Results: Three key findings emerged. First, a minority of songs (13%) contained substance references. Second, the songs with substance references were overwhelmingly (60%) negative, a pattern that increased over time. Third, despite many line-up changes over the band's 43-year period, every song referencing substance use except one featured vocalist Ozzy Osbourne and lyricist Geezer Butler. Conclusion: Contrary to the notion that heavy metal music glorifies or encourages substance use (Record Labeling, United States Senate, 1985), Black Sabbath's lyrics as a whole weave a cautionary tale of how persistent substance use can hijack free will, become the dominant focus of the affected individual, and produce myriad forms of human misery. The insidiousness of chronic substance use depicted by the lyrics mirrors findings from natural-history studies of individuals with substance use disorders and aligns with neurobiological heuristics of addiction. C1 [Conway, Kevin P.] NIDA, 6001 Execut Blvd,Suite 5185, Bethesda, MD 20892 USA. [McGrain, Patrick] Gwynedd Mercy Univ, Gwynedd Valley, PA USA. RP Conway, KP (reprint author), NIDA, 6001 Execut Blvd,Suite 5185, Bethesda, MD 20892 USA. EM kconway@nida.nih.gov OI Conway, Kevin/0000-0002-7638-339X NR 36 TC 0 Z9 0 U1 5 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6084 EI 1532-2491 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2016 VL 51 IS 12 BP 1655 EP 1663 DI 10.1080/10826084.2016.1191515 PG 9 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA DV2KZ UT WOS:000382750700014 PM 27487258 ER PT J AU Williamson, PR AF Williamson, Peter R. TI Role of laccase in the virulence of Talaromyces marneffei: A common link between AIDS-related fungal pathogens? SO VIRULENCE LA English DT Editorial Material DE AIDS; Cryptococcus neoformans; fungus; Histoplasma capsulatum; immunoregulation; pathogen; Talaromyces marneffei; virulence ID PENICILLIUM-MARNEFFEI; CRYPTOCOCCUS-NEOFORMANS; IN-VITRO; INFECTION; MELANIN; MELANIZATION; RECOGNITION; INTERFERON; DIAGNOSIS; LAMININ C1 [Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Williamson, PR (reprint author), NIAID, Bld 10,Rm 11N222,9000 Rockville Pike, Bethesda, MD 20892 USA. EM williamsonpr@mail.nih.gov NR 25 TC 0 Z9 0 U1 2 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2150-5594 EI 2150-5608 J9 VIRULENCE JI Virulence PY 2016 VL 7 IS 6 BP 627 EP 629 DI 10.1080/21505594.2016.1198867 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DU6LH UT WOS:000382325700005 PM 27282335 ER PT J AU Nygaard, RH Maynard, S Schjerling, P Kjaer, M Qvortrup, K Bohr, VA Rasmussen, LJ Jemec, GBE Heidenheim, M AF Nygaard, Rie Harboe Maynard, Scott Schjerling, Peter Kjaer, Michael Qvortrup, Klaus Bohr, Vilhelm A. Rasmussen, Lene J. Jemec, Gregor B. E. Heidenheim, Michael TI Acquired Localized Cutis Laxa due to Increased Elastin Turnover SO CASE REPORTS IN DERMATOLOGY LA English DT Article DE Irregular elastin deposition; Collagen; Dermal aging ID MORPHOGENESIS; ELASTOLYSIS AB Cutis laxa is a rare disease characterized by abnormal skin wrinkling and laxity, due to decreased elastin synthesis or structural extracellular matrix defects. We have explored elastin metabolism in a case of adult onset cutis laxa localized to the upper body of a woman. For this purpose, we obtained skin biopsies from affected and unaffected skin areas of the patient and analyzed these with microscopy, polymerase chain reaction, western blotting and cell culture experiments. Skin from the affected area lacked elastin fibers in electron microscopy but had higher mRNA expression of elastin and total RNA. Levels of an apparent tropoelastin degradation product were higher in the affected area. Fibroblast cultures from the affected area were able to produce elastin and showed higher proliferation and survival after oxidative and UVB stress compared to fibroblasts from the unaffected area. In conclusion, we report a case of acquired localized cutis laxa with a lack of elastic fibers in the skin of the patient's upper body. The lack of elastic fibers in the affected skin was combined with increased mRNA expression and protein levels of elastin. These findings indicate that elastin synthesis was increased but did not lead to deposited elastic fibers in the tissue. (C) 2016 The Author(s) Published by S. Karger AG, Basel C1 [Nygaard, Rie Harboe; Schjerling, Peter; Kjaer, Michael] Bispebjerg Hosp, Inst Sports Med, Dept Orthoped Surg, DK-2400 Copenhagen NV, Denmark. [Nygaard, Rie Harboe; Maynard, Scott; Schjerling, Peter; Kjaer, Michael; Bohr, Vilhelm A.; Rasmussen, Lene J.] Univ Copenhagen, Fac Hlth & Med Sci, Roskilde Hosp, Ctr Hlth Aging, Copenhagen, Denmark. [Maynard, Scott; Bohr, Vilhelm A.; Rasmussen, Lene J.] Univ Copenhagen, Fac Hlth & Med Sci, Roskilde Hosp, Dept Cellular & Mol Med, Copenhagen, Denmark. [Qvortrup, Klaus] Univ Copenhagen, Fac Hlth & Med Sci, Roskilde Hosp, Core Facil Integrated Microscopy, Copenhagen, Denmark. [Jemec, Gregor B. E.; Heidenheim, Michael] Univ Copenhagen, Fac Hlth & Med Sci, Roskilde Hosp, Dept Dermatol, Copenhagen, Denmark. [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Nygaard, RH (reprint author), Bispebjerg Hosp, Inst Sports Med, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark. EM rieharboenielsen@gmail.com NR 12 TC 0 Z9 0 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-6567 J9 CASE REP DERMATOL JI Case Rep. Dermatol. PY 2016 VL 8 IS 1 BP 42 EP 51 DI 10.1159/000443696 PG 10 WC Dermatology SC Dermatology GA DU8GA UT WOS:000382450100010 PM 27293393 ER PT J AU Holl, EK Allen, IC Martinez, J AF Holl, Eda K. Allen, Irving C. Martinez, Jennifer TI Holding the Inflammatory System in Check: TLRs and NLRs SO MEDIATORS OF INFLAMMATION LA English DT Editorial Material C1 [Holl, Eda K.] Duke Univ, Dept Surg, Durham, NC 27710 USA. [Allen, Irving C.] Virginia Tech, Virginia Maryland Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. [Martinez, Jennifer] NIEHS, Immun Inflammat & Dis Lab, POB 12233, Res Triangle Pk, NC 27709 USA. RP Holl, EK (reprint author), Duke Univ, Dept Surg, Durham, NC 27710 USA. EM eda.holl@duke.edu NR 0 TC 0 Z9 0 U1 2 U2 2 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 0962-9351 EI 1466-1861 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PY 2016 AR 8156816 DI 10.1155/2016/8156816 PG 2 WC Cell Biology; Immunology SC Cell Biology; Immunology GA DV1ND UT WOS:000382687000001 ER PT S AU DeStefano, Z Abi-Jaoudeh, N Li, M Wood, BJ Summers, RM Yao, JH AF DeStefano, Zachary Abi-Jaoudeh, Nadine Li, Ming Wood, Bradford J. Summers, Ronald M. Yao, Jianhua BE Webster, RJ Yaniv, ZR TI CT Thermometry for Cone-beam CT Guided Ablation SO MEDICAL IMAGING 2016: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on SPIE Image-Guided Procedures, Robotic Interventions, and Modeling CY FEB 28-MAR 01, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, imXPAD, Siemens, Nat Diagnost Imaging DE Cone-beam CT; CBCT; Thermometry; Radiofrequency Ablation; Time Delay Analysis ID SEGMENTATION AB Monitoring temperature during a cone-beam CT (CBCT) guided ablation procedure is important for prevention of over-treatment and under-treatment. In order to accomplish ideal temperature monitoring, a thermometry map must be generated. Previously, this was attempted using CBCT scans of a pig shoulder undergoing ablation.(1) We are extending this work by using CBCT scans of real patients and incorporating more processing steps. We register the scans before comparing them due to the movement and deformation of organs. We then automatically locate the needle tip and the ablation zone. We employ a robust change metric due to image noise and artifacts. This change metric takes windows around each pixel and uses an equation inspired by Time Delay Analysis to calculate the error between windows with the assumption that there is an ideal spatial offset. Once the change map is generated, we correlate change data with measured temperature data at the key points in the region. This allows us to transform our change map into a thermal map. This thermal map is then able to provide an estimate as to the size and temperature of the ablation zone. We evaluated our procedure on a data set of 12 patients who had a total of 24 ablation procedures performed. We were able to generate reasonable thermal maps with varying degrees of accuracy. The average error ranged from 2.7 to 16.2 degrees Celsius. In addition to providing estimates of the size of the ablation zone for surgical guidance, 3D visualizations of the ablation zone and needle are also produced. C1 [DeStefano, Zachary; Summers, Ronald M.; Yao, Jianhua] NIH, Clin Image Proc Serv, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Abi-Jaoudeh, Nadine; Wood, Bradford J.] NIH, Intervent Radiol, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Li, Ming] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. RP DeStefano, Z (reprint author), NIH, Clin Image Proc Serv, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0021-8 J9 PROC SPIE PY 2016 VL 9786 AR UNSP 978615 DI 10.1117/12.2216302 PG 10 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BF5NO UT WOS:000382315800040 ER PT S AU Potter, M Yaniv, Z AF Potter, Michael Yaniv, Ziv BE Webster, RJ Yaniv, ZR TI Cost-Effective Surgical Registration Using Consumer Depth Cameras SO MEDICAL IMAGING 2016: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on SPIE Image-Guided Procedures, Robotic Interventions, and Modeling CY FEB 28-MAR 01, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, imXPAD, Siemens, Nat Diagnost Imaging DE image-guided procedures; registration; surface acquisition; Microsoft Kinect; 3DSystems Sense ID IMAGE-GUIDED NEUROSURGERY; HEALTH-CARE COSTS; SURGERY; ACCURACY AB The high costs associated with technological innovation have been previously identified as both a major contributor to the rise of health care expenses, and as a limitation for widespread adoption of new technologies. In this work we evaluate the use of two consumer grade depth cameras, the Microsoft Kinect v1 and 3DSystems Sense, as a means for acquiring point clouds for registration. These devices have the potential to replace professional grade laser range scanning devices in medical interventions that do not require sub-millimetric registration accuracy, and may do so at a significantly reduced cost. To facilitate the use of these devices we have developed a near real-time (1-4 sec/frame) rigid registration framework combining several alignment heuristics with the Iterative Closest Point (ICP) algorithm. Using nearest neighbor registration error as our evaluation criterion we found the optimal scanning distances for the Sense and Kinect to be 50-60cm and 70-80cm respectively. When imaging a skull phantom at these distances, RMS error values of 1.35mm and 1.14mm were obtained. The registration framework was then evaluated using cranial MR scans of two subjects. For the first subject, the RMS error using the Sense was 1.28 +/- 0.01 mm. Using the Kinect this error was 1.24 +/- 0.03 mm. For the second subject, whose MR scan was significantly corrupted by metal implants, the errors increased to 1.44 +/- 0.03 mm and 1.74 +/- 0.06 mm but the system nonetheless performed within acceptable bounds. C1 [Potter, Michael; Yaniv, Ziv] NIH, Off High Performance Comp & Commun, Natl Lib Med, Bethesda, MD 20894 USA. [Potter, Michael] Rochester Inst Technol, Deptartment Biomed Engn, Rochester, NY 14623 USA. [Yaniv, Ziv] TAJ Technol Inc, Mendota Hts, MN 55120 USA. RP Potter, M (reprint author), NIH, Off High Performance Comp & Commun, Natl Lib Med, Bethesda, MD 20894 USA.; Potter, M (reprint author), Rochester Inst Technol, Deptartment Biomed Engn, Rochester, NY 14623 USA. EM mjp2010@rit.edu; zivyaniv@nih.gov NR 21 TC 0 Z9 0 U1 3 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0021-8 J9 PROC SPIE PY 2016 VL 9786 AR UNSP 97861W DI 10.1117/12.2217515 PG 13 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BF5NO UT WOS:000382315800066 ER PT S AU Seifabadi, R Xu, S Pinto, P Wood, BJ AF Seifabadi, Reza Xu, Sheng Pinto, Peter Wood, Bradford J. BE Webster, RJ Yaniv, ZR TI A Motorized Ultrasound System for MRI-Ultrasound Fusion Guided Prostatectomy SO MEDICAL IMAGING 2016: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on SPIE Image-Guided Procedures, Robotic Interventions, and Modeling CY FEB 28-MAR 01, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, imXPAD, Siemens, Nat Diagnost Imaging DE Prostatectomy; da Vinci robot; Trasnrectal ultrasound probe holder; MRI-ultrasound fusion ID RADICAL PROSTATECTOMY AB Purpose: This study presents MoTRUS, a motorized transrectal ultrasound system, to enable remote navigation of a transrectal ultrasound (TRUS) probe during da Vinci assisted prostatectomy. MoTRUS not only provides a stable platform to the ultrasound probe, but also allows the physician to navigate it remotely while sitting on the da Vinci console. This study also presents phantom feasibility study with the goal being intraoperative MRI-US image fusion capability to bring preoperative MR images to the operating room for the best visualization of the gland, boundaries, nerves, etc. Method: A two degree-of-freedom probe holder is developed to insert and rotate a bi-plane transrectal ultrasound transducer. A custom joystick is made to enable remote navigation of MoTRUS. Safety features have been considered to avoid inadvertent risks (if any) to the patient. Custom design software has been developed to fuse pre-operative MR images to intraoperative ultrasound images acquired by MoTRUS. Results: Remote TRUS probe navigation was evaluated on a patient after taking required consents during prostatectomy using MoTRUS. It took 10 min to setup the system in OR. MoTRUS provided similar capability in addition to remote navigation and stable imaging. No complications were observed. Image fusion was evaluated on a commercial prostate phantom. Electromagnetic tracking was used for the fusion. Conclusions: Motorized navigation of the TRUS probe during prostatectomy is safe and feasible. Remote navigation provides physician with a more precise and easier control of the ultrasound image while removing the burden of manual manipulation of the probe. Image fusion improved visualization of the prostate and boundaries in a phantom study. C1 [Seifabadi, Reza; Xu, Sheng; Pinto, Peter; Wood, Bradford J.] NIH, Ctr Intervent Oncol, Bldg 10, Bethesda, MD 20892 USA. RP Seifabadi, R (reprint author), NIH, Ctr Intervent Oncol, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0021-8 J9 PROC SPIE PY 2016 VL 9786 AR UNSP 97862H DI 10.1117/12.2217112 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BF5NO UT WOS:000382315800086 ER PT S AU Xu, S Agarwal, H Bernardo, M Seifabadi, R Turkbey, B Partanen, A Negussie, A Glossop, N Choyke, P Pinto, P Wood, BJ AF Xu, Sheng Agarwal, Harsh Bernardo, Marcelino Seifabadi, Reza Turkbey, Baris Partanen, Ari Negussie, Ayele Glossop, Neil Choyke, Peter Pinto, Peter Wood, Bradford J. BE Webster, RJ Yaniv, ZR TI An MRI guided system for prostate laser ablation with treatment planning and multi-planar temperature monitoring SO MEDICAL IMAGING 2016: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on SPIE Image-Guided Procedures, Robotic Interventions, and Modeling CY FEB 28-MAR 01, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, imXPAD, Siemens, Nat Diagnost Imaging DE Ablation; image guidance; prostate cancer; MRI; Treatment planning; Thermometry ID CANCER; THERAPY AB Prostate cancer is often over treated with standard treatment options which impact the patients' quality of life. Laser ablation has emerged as a new approach to treat prostate cancer while sparing the healthy tissue around the tumor. Since laser ablation has a small treatment zone with high temperature, it is necessary to use accurate image guidance and treatment planning to enable full ablation of the tumor. Intraoperative temperature monitoring is also desirable to protect critical structures from being damaged in laser ablation. In response to these problems, we developed a navigation platform and integrated it with a clinical MRI scanner and a side firing laser ablation device. The system allows imaging, image guidance, treatment planning and temperature monitoring to be carried out on the same platform. Temperature sensing phantoms were developed to demonstrate the concept of iterative treatment planning and intraoperative temperature monitoring. Retrospective patient studies were also conducted to show the clinical feasibility of the system. C1 [Xu, Sheng; Bernardo, Marcelino; Seifabadi, Reza; Turkbey, Baris; Negussie, Ayele; Choyke, Peter; Pinto, Peter; Wood, Bradford J.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Agarwal, Harsh] Philips Res North Amer, Briarcliff Manor, NY 10510 USA. [Partanen, Ari] Philips Healthcare, Clin Sci MR Therapy, Andover, MA 01810 USA. [Glossop, Neil] ArciTrax Inc, Toronto, ON M5V 1G3, Canada. RP Xu, S (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0021-8 J9 PROC SPIE PY 2016 VL 9786 AR UNSP 97861I DI 10.1117/12.2216084 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BF5NO UT WOS:000382315800052 ER PT S AU Jung, HM Isogai, S Kamei, M Castranova, D Gore, AV Weinstein, BM AF Jung, H. M. Isogai, S. Kamei, M. Castranova, D. Gore, A. V. Weinstein, B. M. BE Detrich, HW Westerfield, M Zon, LI TI Imaging blood vessels and lymphatic vessels in the zebrafish SO ZEBRAFISH: CELLULAR AND DEVELOPMENTAL BIOLOGY, PT A: CELLULAR BIOLOGY, 4TH EDITION SE Methods in Cell Biology LA English DT Review; Book Chapter ID EMBRYONIC VASCULAR DEVELOPMENT; HEMATOPOIETIC STEM-CELLS; LIGHT-SHEET MICROSCOPY; IN-VIVO; TRANSGENIC ZEBRAFISH; MICROARRAY ANALYSIS; MULTIVIEW DECONVOLUTION; NETWORK FORMATION; REDUNDANT ROLES; EXPRESSION AB Blood vessels supply tissues and organs with oxygen, nutrients, cellular, and humoral factors, while lymphatic vessels regulate tissue fluid homeostasis, immune trafficking, and dietary fat absorption. Understanding the mechanisms of vascular morphogenesis has become a subject of intense clinical interest because of the close association of both types of vessels with pathogenesis of a broad spectrum of human diseases. The zebrafish provides a powerful animal model to study vascular morphogenesis because of their small, accessible, and transparent embryos. These unique features of zebrafish embryos permit sophisticated high-resolution live imaging of even deeply localized vessels during embryonic development and even in adult tissues. In this chapter, we summarize various methods for blood and lymphatic vessel imaging in zebrafish, including nonvital resin injection-based or dye injection-based vessel visualization, and alkaline phosphatase staining. We also provide protocols for vital imaging of vessels using microangiography or transgenic fluorescent reporter zebrafish lines. C1 [Jung, H. M.; Castranova, D.; Gore, A. V.; Weinstein, B. M.] NICHHD, Bethesda, MD 20892 USA. [Isogai, S.] Iwate Med Univ, Morioka, Iwate, Japan. [Kamei, M.] South Australian Hlth & Med Res Inst, Adelaide, SA, Australia. RP Weinstein, BM (reprint author), NICHHD, Bethesda, MD 20892 USA. EM flyingfish@nih.gov OI Kamei, Makoto/0000-0002-1438-0783 NR 78 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-803489-7; 978-0-12-803475-0 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2016 VL 133 BP 69 EP 103 DI 10.1016/bs.mcb.2016.03.023 PG 35 WC Cell Biology; Marine & Freshwater Biology SC Cell Biology; Marine & Freshwater Biology GA BF5OS UT WOS:000382401100005 PM 27263409 ER PT S AU Zhang, QX He, XJ Wong, HC Kindt, KS AF Zhang, Q. X. He, X. J. Wong, H. C. Kindt, K. S. BE Detrich, HW Westerfield, M Zon, LI TI Functional calcium imaging in zebrafish lateral-line hair cells SO ZEBRAFISH: CELLULAR AND DEVELOPMENTAL BIOLOGY, PT A: CELLULAR BIOLOGY, 4TH EDITION SE Methods in Cell Biology LA English DT Review; Book Chapter ID ENCODED CA2+ INDICATORS; FLUORESCENT PROTEINS; NEURONAL-ACTIVITY; MECHANOTRANSDUCTION; CHANNEL; TRANSDUCTION; MECHANISMS; RESOLUTION; CALMODULIN; RECORDINGS AB Sensory hair-cell development, function, and regeneration are fundamental processes that are challenging to study inmammalian systems. Zebrafish are an excellent alternative model to study hair cells because they have an external auxiliary organ called the lateral line. The hair cells of the lateral line are easily accessible, which makes them suitable for live, function-based fluorescence imaging. In this chapter, we describe methods to perform functional calcium imaging in zebrafish lateral-line hair cells. We compare genetically encoded calcium indicators that have been used previously to measure calcium in lateral-line hair cells. We also outline equipment required for calcium imaging and compare different imaging systems. Lastly, we discuss how to set up optimal imaging parameters and how to process and visualize calcium signals. Overall, using these methods, in vivo calcium imaging is a powerful tool to examine sensory hair-cell function in an intact organism. C1 [Zhang, Q. X.; He, X. J.; Wong, H. C.; Kindt, K. S.] NIDCD, NIH, Bethesda, MD 20850 USA. RP Kindt, KS (reprint author), NIDCD, NIH, Bethesda, MD 20850 USA. EM katie.kindt@nih.gov OI He, Jenny/0000-0002-3884-0596 NR 49 TC 1 Z9 1 U1 3 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-803489-7; 978-0-12-803475-0 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2016 VL 133 BP 229 EP 252 DI 10.1016/bs.mcb.2015.12.002 PG 24 WC Cell Biology; Marine & Freshwater Biology SC Cell Biology; Marine & Freshwater Biology GA BF5OS UT WOS:000382401100011 PM 27263415 ER PT S AU Lenstra, TL Rodriguez, J Chen, HM Larson, DR AF Lenstra, Tineke L. Rodriguez, Joseph Chen, Huimin Larson, Daniel R. BE Dill, KA TI Transcription Dynamics in Living Cells SO ANNUAL REVIEW OF BIOPHYSICS, VOL 45 SE Annual Review of Biophysics LA English DT Review; Book Chapter DE single-molecule; single-cell; kinetics; bursting; heterogeneity; imaging; fluorescence ID RNA-POLYMERASE-II; EUKARYOTIC GENE-EXPRESSION; EMBRYONIC STEM-CELLS; MESSENGER-RNA; REAL-TIME; LIVE CELLS; DROSOPHILA EMBRYOS; NASCENT RNA; IN-VIVO; DEPENDENT TRANSCRIPTION AB The transcription cycle can be roughly divided into three stages: initiation, elongation, and termination. Understanding the molecular events that regulate all these stages requires a dynamic view of the underlying processes. The development of techniques to visualize and quantify transcription in single living cells has been essential in revealing the transcription kinetics. They have revealed that (a) transcription is heterogeneous between cells and (b) transcription can be discontinuous within a cell. In this review, we discuss the progress in our quantitative understanding of transcription dynamics in living cells, focusing on all parts of the transcription cycle. We present the techniques allowing for single-cell transcription measurements, review evidence from different organisms, and discuss how these experiments have broadened our mechanistic understanding of transcription regulation. C1 [Lenstra, Tineke L.; Rodriguez, Joseph; Chen, Huimin; Larson, Daniel R.] NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, Bethesda, MD 20892 USA. RP Larson, DR (reprint author), NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, Bethesda, MD 20892 USA. EM dan.larson@nih.gov RI Larson, Daniel/B-9829-2008 OI Larson, Daniel/0000-0001-9253-3055 NR 139 TC 1 Z9 1 U1 14 U2 16 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1936-122X BN 978-0-8243-1845-1 J9 ANNU REV BIOPHYS JI Annu. Rev. Biophys. PY 2016 VL 45 BP 25 EP 47 DI 10.1146/annurev-biophys-062215-010838 PG 23 WC Biophysics SC Biophysics GA BF5HY UT WOS:000382010600002 PM 27145880 ER PT J AU Jarungkitkul, W Sukcharoensin, S AF Jarungkitkul, Wanida Sukcharoensin, Sorasart TI Benchmarking the competitiveness of the ASEAN 5 equity markets An application of Porter's diamond model SO BENCHMARKING-AN INTERNATIONAL JOURNAL LA English DT Article DE Benchmarking; Competitive advantage; ASEAN; Stock markets ID RESOURCE-BASED VIEW; FIRM AB Purpose - The purpose of this paper is to study the competitiveness of the stock markets in ASEAN 5, which are the Stock Exchange of Thailand (SET), the Singapore Exchange (SGX), Bursa Malaysia (BM), the Indonesia Stock Exchange (IDX), and the Philippine Stock Exchange (PSE). Design/methodology/approach - This research applies Porter's (1990) diamond model to analyze the competitiveness and the data were collected from World Economic Forum, International Institute for Management Development, the World Federation of Exchanges database, and DataStream. Findings - The results show that SGX is the most competitive exchange in ASEAN 5 region. It dominates other exchanges in every dimension. It gains its reputation for being the region's most prominent exchange, followed by BM, SET, IDX, and the PSE, respectively. Practical implications - The results of this investigation provide rank for competitiveness of stock exchanges among ASEAN 5 and identify the way to improve its competitive position. Social implications - It is useful for public and private sectors involved in the development and policy making to promote funding and investment efficiency of the exchanges. It will be benefit to establish the well-planned development strategy and policy to build up the competitive advantage of the nations. Originality/value - Identifying and benchmarking the competitiveness of the stock markets in ASEAN economies. By using Diamond Model, the authors propose indicators to assess the competitiveness of the stock markets in ASEAN 5 countries. Assessing the competitiveness of the ASEAN stock markets in this paper will lead us to better understand about each country's strengths and weaknesses and to promote a mutual collaboration among the region toward ASEAN Economic Community. C1 [Jarungkitkul, Wanida] NIDA, Sch Dev Econ, Grad Sch Dev Econ, Finance Econ, Bangkok, Thailand. [Sukcharoensin, Sorasart] NIDA, Sch Dev Econ, Grad Sch Dev Econ, Acad Affairs, Bangkok, Thailand. RP Sukcharoensin, S (reprint author), NIDA, Sch Dev Econ, Grad Sch Dev Econ, Acad Affairs, Bangkok, Thailand. EM sorasart@nida.ac.th NR 47 TC 0 Z9 0 U1 4 U2 4 PU EMERALD GROUP PUBLISHING LTD PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY BD16 1WA, W YORKSHIRE, ENGLAND SN 1463-5771 EI 1758-4094 J9 BENCHMARKING JI Benchmarking PY 2016 VL 23 IS 5 BP 1312 EP 1340 DI 10.1108/BIJ-05-2014-0047 PG 29 WC Management SC Business & Economics GA DU1AE UT WOS:000381936300013 ER PT J AU Tassiopoulos, K Patel, K Alperen, J Kacanek, D Ellis, A Berman, C Allison, SM Hazra, R Barr, E Cantos, K Siminski, S Massagli, M Bauermeister, J Siddiqui, DQ Puga, A Van Dyke, R Seage, GR AF Tassiopoulos, Katherine Patel, Kunjal Alperen, Julie Kacanek, Deborah Ellis, Angela Berman, Claire Allison, Susannah M. Hazra, Rohan Barr, Emily Cantos, Krystal Siminski, Suzanne Massagli, Michael Bauermeister, Jose Siddiqui, Danish Q. Puga, Ana Van Dyke, Russell Seage, George R., III CA Pediat HIV AIDS Cohort Study TI Following young people with perinatal HIV infection from adolescence into adulthood: the protocol for PHACS AMP Up, a prospective cohort study SO BMJ OPEN LA English DT Article DE EPIDEMIOLOGY; PUBLIC HEALTH ID HUMAN-IMMUNODEFICIENCY-VIRUS; PEDIATRIC HIV/AIDS COHORT; ANTIRETROVIRAL TREATMENT; UNINFECTED CHILDREN; ACQUIRED HIV; HEALTH-CARE; WEB; THERAPY; YOUTH; EPIDEMIOLOGY AB Introduction The first generation of adolescents born with HIV infection has reached young adulthood due to advances in treatment. It is important to continue follow-up of these individuals to assess their long-term medical, behavioural and mental health and ability to successfully transition to adulthood while coping with a chronic, potentially stigmatising condition. To accomplish this, and to maintain their interest in long-term research participation, we need to accommodate the changing lifestyles and interests of young adult study participants while ensuring valid data collection. We report the protocol for Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP) Up, a prospective cohort study enrolling young adult participants for long-term follow-up. Methods and analysis AMP Up is recruiting 850 young men and women 18years of age and older600 perinatally HIV-infected and a comparison group of 250 perinatally HIV-exposed, uninfectedat 14 clinical research sites in the USA and Puerto Rico. Recruitment began in April 2014 and is ongoing, with 305 participants currently enrolled. Planned follow-up is 6years. Data are collected with a flexible hybrid of online and in-person methods. Outcomes include: transition to adult clinical care and retention in care; end-organ diseases; malignancies; metabolic complications; sexually transmitted infections; reproductive health; mental health and neurocognitive functioning; adherence to antiretroviral treatment; sexual behaviour and substance use; hearing and language impairments; and employment and educational achievement. Ethics and dissemination The study received ethical approval from the Harvard T.H. Chan School of Public Health's institutional review board (IRB), and from the IRBs of each clinical research site. All participants provide written informed consent; for cognitively impaired individuals with legally authorised representatives, legal guardian permission and participant assent is obtained. Findings will be disseminated through peer-reviewed journals, conference presentations and participant summaries. C1 [Tassiopoulos, Katherine; Patel, Kunjal; Alperen, Julie; Berman, Claire; Cantos, Krystal; Massagli, Michael; Seage, George R., III] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Kacanek, Deborah] Harvard TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA USA. [Ellis, Angela; Siminski, Suzanne] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. [Allison, Susannah M.] NIMH, Div AIDS Res, NIH, Bethesda, MD 20892 USA. [Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD USA. [Barr, Emily] Univ Colorado, Childrens Hosp Colorado, Dept Pediat Infect Dis, Aurora, CO USA. [Bauermeister, Jose] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Siddiqui, Danish Q.; Van Dyke, Russell] Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. [Puga, Ana] Childrens Diagnost & Treatment Ctr Inc, Ft Lauderdale, FL USA. RP Tassiopoulos, K (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. EM ktassiop@hsph.harvard.edu OI Bauermeister, Jose/0000-0002-9276-2306 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Drug Abuse; National Institute of Allergy and Infectious Diseases; Office of AIDS Research; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Heart Lung and Blood Institute; National Institute of Dental and Craniofacial Research; National Institute on Alcohol Abuse and Alcoholism; Harvard T.H. Chan School of Public Health [HD052102]; Tulane University School of Medicine [HD052104] FX The Pediatric HIV/AIDS Cohort Study (PHACS) was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with cofunding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, and the National Institute on Alcohol Abuse and Alcoholism, through cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102) and the Tulane University School of Medicine (HD052104). Note: The conclusions and opinions expressed in this article are those of the authors and do not necessarily reflect those of the National Institutes of Health or the US Department of Health and Human Services. NR 39 TC 0 Z9 0 U1 3 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2016 VL 6 IS 6 AR e011396 DI 10.1136/bmjopen-2016-011396 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DR9ST UT WOS:000380237100127 PM 27288383 ER PT J AU Rukumnuaykit, P Pholphirul, P AF Rukumnuaykit, Pungpond Pholphirul, Piriya TI Happiness from social capital: An investigation from micro data in rural Thailand SO COMMUNITY DEVELOPMENT LA English DT Article DE Community; happiness; social capital; Thailand ID WELFARE; UTILITY; NETWORKS; CHILDREN; AFRICA; GROWTH; INCOME AB Happiness is a mental or emotional state of wellbeing defined by positive or pleasant emotions ranging from contentment to intense joy. This article aims to investigate the impacts of social capital on individual wellbeing using happiness level (0-10 = highest) as a measure of subjective wellbeing and analyzing micro-level data from rural Thailand. We find significant effects of the perception of individual's social capital, while the effects of community-level social capital are found to have insignificant effects on happiness. Our findings confirm that living in a household or community in which other members are, on average, happy, would cause the person to be happy. The findings suggest that an individual's subjective perceptions of social capital, especially trusting others and participating in community public meetings, are important indicators that affect happiness at the individual level. C1 [Rukumnuaykit, Pungpond] Chulalongkorn Univ, Coll Populat Studies, Bangkok, Thailand. [Pholphirul, Piriya] NIDA, Grad Sch Dev Econ, Bangkok, Thailand. RP Pholphirul, P (reprint author), NIDA, Grad Sch Dev Econ, Bangkok, Thailand. EM piriya@nida.ac.th NR 43 TC 0 Z9 0 U1 4 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1557-5330 EI 1944-7485 J9 COMMUNITY DEV JI Community Dev. PY 2016 VL 47 IS 4 BP 562 EP 573 DI 10.1080/15575330.2016.1206584 PG 12 WC Planning & Development SC Public Administration GA DT9GU UT WOS:000381805900011 ER PT J AU Santiago, HD Nutman, TB AF Santiago, Helton da Costa Nutman, Thomas B. TI Role in Allergic Diseases of Immunological Cross-Reactivity between Allergens and Homologues of Parasite Proteins SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE hygiene hypothesis; cross-reactivity; allergen; allergy; helminth ID REGULATORY T-CELLS; GLUTATHIONE S-TRANSFERASES; SKIN-TEST REACTIVITY; HELMINTH INFECTION; HOOKWORM INFECTION; DENDRITIC CELLS; INTESTINAL PARASITES; ASCARIS-LUMBRICOIDES; HYGIENE HYPOTHESIS; SCHOOL-CHILDREN AB Implied under the rubric of the hygiene hypothesis is that helminth infection can protect against allergic disease. It is well known that helminths induce processes associated with type 2 immune responses, but they also induce important regulatory responses that can modulate these type 2-associated responses-modulation that influences responses to bystander antigens including allergens. Indeed, most epidemiological studies demonstrate a beneficial effect of helminth infection on atopy, but there are also convincing data to demonstrate that helminth infection can precipitate or worsen allergic inflammation/disease. Reasons for these disparate findings are much debated, but there is a school of thought that suggests that helminth-triggered type 2-associated responses, including IgE to cross-reactive aeroallergens, can offset the regulatory effects imposed by the same organisms. The cross-reactivity among helminths and allergenic tropomyosins dominated the antigen/allergen cross-reactivity field, but recent data suggest that cross-reactivity is much more common than previously appreciated. It has been demonstrated that a high degree of molecular similarity exists between allergens and helminth proteins. Thus, an understanding of the mechanisms underlying the response induced by helminth infection and their impact on the induction of allergic disease in the host are critical for designing therapies using iatrogenic infections or parasite products to treat inflammatory diseases and for developing vaccines against helminth parasites. C1 [Santiago, Helton da Costa] Univ Fed Minas Gerais, Dept Biochem & Immunol, Belo Horizonte, MG, Brazil. [Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA. RP Santiago, HD (reprint author), Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Ave Antonio Carlos 6627, Belo Horizonte, MG, Brazil. EM heltonsantiago@icb.ufmg.br FU Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID); Conselho Nacional de Pesquisa (CNPq); Fundacao de Amparo a Pesquisa de Minas Gerais (FAPEMIG) FX This work was supported, in part, by the Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID); Conselho Nacional de Pesquisa (CNPq); and Fundacao de Amparo a Pesquisa de Minas Gerais (FAPEMIG). NR 118 TC 0 Z9 0 U1 4 U2 4 PU BEGELL HOUSE INC PI DANBURY PA 50 NORTH ST, DANBURY, CT 06810 USA SN 1040-8401 EI 2162-6472 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2016 VL 36 IS 1 BP 1 EP 11 DI 10.1615/CritRevImmunol.2016016545 PG 11 WC Immunology SC Immunology GA DS4VK UT WOS:000380779500001 ER PT J AU Chan, GNY Goldstein, JA Miller, DS AF Chan, Gary N. Y. Goldstein, Joyce A. Miller, David S. TI High glucose reduces P-glycoprotein transport activity at the blood-brain barrier SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 20th North American Meeting of the International-Society-for-the-Study-of-Xenobiotics (ISSX) CY OCT 18-22, 2015 CL Orlando, FL SP Int Soc Study Xenobiot C1 [Chan, Gary N. Y.; Goldstein, Joyce A.; Miller, David S.] NIEHS, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0360-2532 EI 1097-9883 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2016 VL 48 SU 1 MA P256 BP 146 EP 146 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DS4IO UT WOS:000380744900303 ER PT J AU Ross, A Brooks, A Touchton-Leonard, K Wallen, G AF Ross, A. Brooks, A. Touchton-Leonard, K. Wallen, G. TI A Different Weight Loss Experience: A Qualitative Study Exploring the Behavioral, Physical, and Psychosocial Changes Associated with Yoga That Promote Weight Loss SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article ID HEALTH-BENEFITS; OBESITY; WOMEN; MEN AB Yoga interventions improve obesity-related outcomes including body mass index (BMI), body weight, body fat, and waist circumference, yet it is unclear whether these improvements are due to increased physical activity, increased lean muscle mass, and/or changes in eating behaviors. The purpose of this study is to expand our understanding of the experience of losing weight through yoga. Methods. Semistructured interviews were qualitatively analyzed using a descriptive phenomenological approach. Results. Two distinct groups who had lost weight through yoga responded: those who were overweight and had repeatedly struggled in their attempts to lose weight (55%, n = 11) and those who were of normal weight and had lost weight unintentionally (45%, n = 9). Five themes emerged that differed slightly by group: shift toward healthy eating, impact of the yoga community/yoga culture, physical changes, psychological changes, and the belief that the yoga weight loss experience was different than past weight loss experiences. Conclusions. These findings imply that yoga could offer diverse behavioral, physical, and psychosocial effects that may make it a useful tool for weight loss. Role modeling and social support provided by the yoga community may contribute to weight loss, particularly for individuals struggling to lose weight. C1 [Ross, A.; Brooks, A.; Touchton-Leonard, K.; Wallen, G.] NIH, Dept Nursing Res & Translat Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. RP Ross, A (reprint author), NIH, Dept Nursing Res & Translat Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM alyson.ross@nih.gov FU Intramural Research Program of the NIH Clinical Center FX This research was supported [in part] by the Intramural Research Program of the NIH Clinical Center. NR 34 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 1741-427X EI 1741-4288 J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2016 AR 2914745 DI 10.1155/2016/2914745 PG 11 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA DU2IN UT WOS:000382034600001 ER PT J AU Moreno, P Ramos-Alvarez, I Moody, TW Jensen, RT AF Moreno, Paola Ramos-Alvarez, Irene Moody, Terry W. Jensen, Robert T. TI Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE Bombesin; cancer; targeted therapy; nanoparticles; gastrin-releasing peptide; prostate cancer; breast cancer; lung cancer; CNS tumor ID GASTRIN-RELEASING-PEPTIDE; CELL LUNG-CANCER; HUMAN PROSTATE-CANCER; PH-SENSITIVE LIPOSOMES; IN-VIVO EVALUATION; RECEPTOR-EXPRESSING MALIGNANCIES; GROWTH-FACTOR RECEPTOR; GRPR-POSITIVE TUMORS; BREAST-CANCER; HIGH-AFFINITY AB Introduction: Despite remarkable advances in tumor treatment, many patients still die from common tumors (breast, prostate, lung, CNS, colon, and pancreas), and thus, new approaches are needed. Many of these tumors synthesize bombesin (Bn)-related peptides and over-express their receptors (BnRs), hence functioning as autocrine-growth-factors. Recent studies support the conclusion that Bn-peptides/BnRs are well-positioned for numerous novel antitumor treatments, including interrupting autocrinegrowth and the use of over-expressed receptors for imaging and targeting cytotoxic-compounds, either by direct-coupling or combined with nanoparticle-technology. Areas covered: The unique ability of common neoplasms to synthesize, secrete, and show a growth/proliferative/differentiating response due to BnR over-expression, is reviewed, both in general and with regard to the most frequently investigated neoplasms (breast, prostate, lung, and CNS). Particular attention is paid to advances in the recent years. Also considered are the possible therapeutic approaches to the growth/ differentiation effect of Bn-peptides, as well as the therapeutic implication of the frequent BnR over-expression for tumor-imaging and/or targeted-delivery. Expert opinion: Given that Bn-related-peptides/BnRs are so frequently ectopically-expressed by common tumors, which are often malignant and become refractory to conventional treatments, therapeutic interventions using novel approaches to Bn-peptides and receptors are being explored. Of particular interest is the potential of reproducing with BnRs in common tumors the recent success of utilizing overexpression of somatostatin-receptors by neuroendocrine-tumors to provide the most sensitive imaging methods and targeted delivery of cytotoxic-compounds. C1 [Moreno, Paola; Ramos-Alvarez, Irene; Jensen, Robert T.] NIDDK, Digest Dis Branch, Cell Biol Sect, NIH, Bldg 10,Room 9C-103, Bethesda, MD 20892 USA. [Moody, Terry W.] NCI, Ctr Canc Res, Off Director, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, Cell Biol Sect, NIH, Bldg 10,Room 9C-103, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Cancer Institute (NCI), National Institutes of Health (NIH) FX This study was supported by intramural funds of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Cancer Institute (NCI), National Institutes of Health (NIH). 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 208 TC 3 Z9 3 U1 5 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1472-8222 EI 1744-7631 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PY 2016 VL 20 IS 9 BP 1055 EP 1073 DI 10.1517/14728222.2016.1164694 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DU1BR UT WOS:000381941500004 PM 26981612 ER PT J AU Alves, VM Muratov, EN Capuzzi, SJ Politi, R Low, Y Braga, RC Zakharov, AV Sedykh, A Mokshyna, E Farag, S Andrade, CH Kuz'min, VE Fourches, D Tropsha, A AF Alves, Vinicius M. Muratov, Eugene N. Capuzzi, Stephen J. Politi, Regina Low, Yen Braga, Rodolpho C. Zakharov, Alexey V. Sedykh, Alexander Mokshyna, Elena Farag, Sherif Andrade, Carolina H. Kuz'min, Victor E. Fourches, Denis Tropsha, Alexander TI Alarms about structural alerts SO GREEN CHEMISTRY LA English DT Article ID READ-ACROSS; QSAR MODELS; SIMPLEX REPRESENTATION; MOLECULAR-STRUCTURE; SKIN SENSITIZATION; CHEMICAL-STRUCTURE; TOXICITY; PREDICTION; CARCINOGENICITY; NITROAROMATICS AB Structural alerts are widely accepted in chemical toxicology and regulatory decision support as a simple and transparent means to flag potential chemical hazards or group compounds into categories for read-across. However, there has been a growing concern that alerts disproportionally flag chemicals as toxic, which questions their reliability as toxicity markers. Conversely, rigorously developed and properly validated statistical QSAR models can accurately and reliably predict the toxicity of a chemical; however, their use in regulatory toxicology has been hampered by a lack of transparency and interpretability. We demonstrate that contrary to the common perception of QSAR models as "black boxes" they can be used to identify statistically significant chemical substructures (QSAR-based alerts) that influence toxicity. We show through several case studies, however, that the mere presence of structural alerts in a chemical, irrespective of the derivation method (expert-based or QSAR-based), should be perceived only as hypotheses of possible toxicological effect. We propose a new approach that synergistically integrates structural alerts and rigorously validated QSAR models for a more transparent and accurate safety assessment of new chemicals. C1 [Alves, Vinicius M.; Muratov, Eugene N.; Capuzzi, Stephen J.; Politi, Regina; Farag, Sherif; Tropsha, Alexander] Univ N Carolina, Lab Mol Modeling, Div Chem Biol & Med Chem, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. [Alves, Vinicius M.; Braga, Rodolpho C.; Andrade, Carolina H.] Univ Fed Goias, Dept Pharm, Lab Mol Modeling & Design, BR-74605170 Goiania, Go, Brazil. [Muratov, Eugene N.] Odessa Natl Polytech Univ, Dept Chem Technol, UA-65000 Odessa, Ukraine. [Low, Yen] Netflix, San Francisco, CA 94123 USA. [Zakharov, Alexey V.] NIH, NCATS, Rockville, MD 20850 USA. [Sedykh, Alexander] Sciome LLC, Res Triangle Pk, NC 27709 USA. [Mokshyna, Elena; Kuz'min, Victor E.] NAS Ukraine, AV Bogatsky Phys Chem Inst, Lab Theoret Chem, UA-65080 Odessa, Ukraine. [Fourches, Denis] North Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA. [Fourches, Denis] North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA. RP Tropsha, A (reprint author), Univ N Carolina, Lab Mol Modeling, Div Chem Biol & Med Chem, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. EM alex_tropsha@unc.edu FU NIH [GM096967]; FAPEG [201310267001095]; CNPq [400760/2014-2]; CAPES FX This study was supported in part by NIH (GM096967). VA thanks FAPEG (grant 201310267001095), CNPq (grant 400760/2014-2), and CAPES. NR 70 TC 2 Z9 2 U1 3 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9262 EI 1463-9270 J9 GREEN CHEM JI Green Chem. PY 2016 VL 18 IS 16 BP 4348 EP 4360 DI 10.1039/c6gc01492e PG 13 WC Chemistry, Multidisciplinary; GREEN & SUSTAINABLE SCIENCE & TECHNOLOGY SC Chemistry; Science & Technology - Other Topics GA DT4HM UT WOS:000381440800004 ER PT J AU Grimm, FA Iwata, Y Sirenko, O Chappell, GA Wright, FA Reif, DM Braisted, J Gerhold, DL Yeakley, JM Shepard, P Seligmann, B Roy, T Boogaard, PJ Ketelslegers, HB Rohde, AM Rusyn, I AF Grimm, Fabian A. Iwata, Yasuhiro Sirenko, Oksana Chappell, Grace A. Wright, Fred A. Reif, David M. Braisted, John Gerhold, David L. Yeakley, Joanne M. Shepard, Peter Seligmann, Bruce Roy, Tim Boogaard, Peter J. Ketelslegers, Hans B. Rohde, Arlean M. Rusyn, Ivan TI A chemical-biological similarity-based grouping of complex substances as a prototype approach for evaluating chemical alternatives SO GREEN CHEMISTRY LA English DT Article ID BOILING PETROLEUM SUBSTANCES; PLURIPOTENT STEM-CELLS; RING CLASS PROFILE; READ-ACROSS; IN-VITRO; DEVELOPMENTAL TOXICITY; SAFETY ASSESSMENT; ASSAYS; CARDIOTOXICITY; DESCRIPTORS AB Comparative assessment of potential human health impacts is a critical step in evaluating both chemical alternatives and existing products on the market. Most alternatives assessments are conducted on a chemical-by-chemical basis and it is seldom acknowledged that humans are exposed to complex products, not individual substances. Indeed, substances of Unknown or Variable composition, Complex reaction products, and Biological materials (UVCBs) are ubiquitous in commerce yet they present a major challenge for registration and health assessments. Here, we present a comprehensive experimental and computational approach to categorize UVCBs according to global similarities in their bioactivity using a suite of in vitro models. We used petroleum substances, an important group of UVCBs which are grouped for regulatory approval and read-across primarily on physico-chemical properties and the manufacturing process, and only partially based on toxicity data, as a case study. We exposed induced pluripotent stem cell-derived cardiomyocytes and hepatocytes to DMSO-soluble extracts of 21 petroleum substances from five product groups. Concentration-response data from high-content imaging in cardiomyocytes and hepatocytes, as well as targeted high-throughput transcriptomic analysis of the hepatocytes, revealed distinct groups of petroleum substances. Data integration showed that bioactivity profiling affords clustering of petroleum substances in a manner similar to the manufacturing process-based categories. Moreover, we observed a high degree of correlation between bioactivity profiles and physico-chemical properties, as well as improved groupings when chemical and biological data were combined. Altogether, we demonstrate how novel in vitro screening approaches can be effectively utilized in combination with physico-chemical characteristics to group complex substances and enable read-across. This approach allows for rapid and scientifically-informed evaluation of health impacts of both existing substances and their chemical alternatives. C1 [Grimm, Fabian A.; Iwata, Yasuhiro; Chappell, Grace A.; Rusyn, Ivan] Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA. [Sirenko, Oksana] Mol Devices LLC, Sunnyvale, CA USA. [Wright, Fred A.; Reif, David M.] North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA. [Braisted, John; Gerhold, David L.] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA. [Yeakley, Joanne M.; Shepard, Peter; Seligmann, Bruce] BioSpyder Technol Inc, Carlsbad, CA USA. [Roy, Tim] Univ South Carolina, Dept Nat Sci, Beaufort, SC USA. [Boogaard, Peter J.] SHELL Int BV, Houston, TX USA. [Ketelslegers, Hans B.] European Petr Refiners Assoc, Concawe Div, Brussels, Belgium. [Rohde, Arlean M.] ExxonMobil Chem Co, Spring, TX USA. RP Rusyn, I (reprint author), Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA. EM irusyn@cvm.tamu.edu RI Rusyn, Ivan/S-2426-2016 FU United States Environmental Protection Agency [STAR RD83516601, RD83574701]; National Institutes of Health [P42 ES005948]; Intramural Research Program of the NIH, National Center for Advancing Translational Sciences; Society of Toxicology-Colgate Palmolive postdoctoral fellowship FX This work was funded by grants from the United States Environmental Protection Agency (STAR RD83516601 and RD83574701) and the National Institutes of Health (P42 ES005948) and was supported, in part, by the Intramural Research Program of the NIH, National Center for Advancing Translational Sciences. F. Grimm was the recipient of the 2015 Society of Toxicology-Colgate Palmolive postdoctoral fellowship in in vitro toxicology. The authors appreciate useful discussions and technical support from Carole Crittenden (Molecular Devices LLC., Sunnyvale, CA), Joel McComb (BioSpyder Technologies Inc., Carlsbad, CA), and Yi-Hui Zhou (North Carolina State University). NR 39 TC 0 Z9 0 U1 2 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9262 EI 1463-9270 J9 GREEN CHEM JI Green Chem. PY 2016 VL 18 IS 16 BP 4407 EP 4419 DI 10.1039/c6gc01147k PG 13 WC Chemistry, Multidisciplinary; GREEN & SUSTAINABLE SCIENCE & TECHNOLOGY SC Chemistry; Science & Technology - Other Topics GA DT4HM UT WOS:000381440800008 PM 28035192 ER PT J AU Sassi, C Capozzo, R Gibbs, R Crews, C Zecca, C Arcuti, S Copetti, M Barulli, MR Brescia, V Singleton, AB Logroscino, G AF Sassi, Celeste Capozzo, Rosa Gibbs, Raphael Crews, Cynthia Zecca, Chiara Arcuti, Simona Copetti, Massimiliano Barulli, Maria R. Brescia, Vincenzo Singleton, Andrew B. Logroscino, Giancarlo TI A Novel Splice-Acceptor Site Mutation in GRN (c.709-2 A > T) Causes Frontotemporal Dementia Spectrum in a Large Family from Southern Italy SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; frontotemporal dementia; progranulin; splice site mutation ID LOBAR DEGENERATION; PROGRANULIN-MUTATION; ALZHEIMERS-DISEASE; SEQUENCING DATA; IN-VIVO; PLASMA; TAU; INCLUSIONS; MISSENSE; HETEROGENEITY AB Heterozygous loss of function mutations in granulin represent a significant cause of frontotemporal lobar degeneration with ubiquitin and TDP-43 inclusions (FTLD-TDP). We report a novel GRN splice site mutation (c. 709-2 A> T), segregating with frontotemporal dementia spectrum in a large family from southern Italy. The GRN c. 709-2 A> T is predicted to result in the skipping of exon 8, leading to non-sense mediated mRNA decay. Moreover, the PGRN plasma levels in the GRN c. 709-2 A> T carriers were significantly lower (24 ng/ml) compared to controls (142.7 ng/ml) or family members non-carriers (82.0 ng/ml) (p-value = 0.005, KruskalWallis), suggesting progranulin haploinsufficiency. We do not report any potential pathogenic GRN mutation in a follow-up cohort composed of 6 FTD families and 43 sporadic FTD cases, from the same geographic area. Our study suggests that GRN (c. 709-2 A> T) is a novel and likely very rare cause of FTD in this Italian cohort. Finally, in line with previous studies, we show that GRN haploinsufficiency leads to a heterogeneous clinical picture, and plasma progranulin levels may be a reliable tool to identify GRN loss of function mutations. However, given that a) genetic and environmental factors, gender, and age may regulate PGRN plasma levels and b) plasma progranulin levels may not reflect PGRN levels in the central nervous system, we suggest that the measurement of progranulin in the plasma should always be coupled with genetic screening of GRN for mutations. C1 [Sassi, Celeste; Gibbs, Raphael; Crews, Cynthia; Singleton, Andrew B.] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA. [Sassi, Celeste] UCL Inst Neurol, Dept Mol Neurosci, Reta Lila Weston Res Labs, London, England. [Sassi, Celeste; Capozzo, Rosa; Zecca, Chiara] Charite, Ctr Stroke Res Berlin CSB, Dept Expt Neurol, Berlin, Germany. [Sassi, Celeste] German Ctr Neurodegenerat Dis DZNE, Berlin, Germany. [Arcuti, Simona; Logroscino, Giancarlo] Univ Bari, Pia Fdn Card G Panico Hosp, Dept Clin Res Neurol, Via S Pio 4, I-73039 Lecce, Italy. [Copetti, Massimiliano] IRCCS Casa Sollievo Sofferenza, Biostat Unit, San Giovanni Rotondo, Italy. [Barulli, Maria R.; Brescia, Vincenzo] Pia Fdn Card G Panico, Unit Lab Med, Lecce, Italy. RP Logroscino, G (reprint author), Univ Bari, Pia Fdn Card G Panico Hosp, Dept Clin Res Neurol, Via S Pio 4, I-73039 Lecce, Italy. EM giancarlo.logroscino@gmail.com RI Arcuti, Simona/J-8587-2016; COPETTI, MASSIMILIANO/K-3186-2016 OI Arcuti, Simona/0000-0002-0132-3296; COPETTI, MASSIMILIANO/0000-0002-7960-5947 FU Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services [ZO1 AG000951] FX This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services; project number ZO1 AG000951, to Dr. Andrew Singleton. NR 37 TC 0 Z9 0 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2016 VL 53 IS 2 BP 475 EP 485 DI 10.3233/JAD-151170 PG 11 WC Neurosciences SC Neurosciences & Neurology GA DT0XY UT WOS:000381207500009 PM 27258413 ER PT J AU Decker, AM Partilla, JS Baumann, MH Rothman, RB Blough, BE AF Decker, Ann M. Partilla, John S. Baumann, Michael H. Rothman, Richard B. Blough, Bruce E. TI The biogenic amine transporter activity of vinylogous amphetamine analogs SO MEDCHEMCOMM LA English DT Article ID TERM SEROTONIN DEPLETION; MONOAMINE TRANSPORTERS; RAT-BRAIN; RHESUS-MONKEYS; NEUROTRANSMITTER TRANSPORTERS; COCAINE-DEPENDENCE; STIMULANT ABUSE; AGONIST-LIKE; FENFLURAMINE; RELEASERS AB A series of vinylogous amphetamine analogs was synthesized and examined for their activity at biogenic amine transporters and serotonin-2 receptor (5-HT2) subtypes. (1S,3E)-1-Methyl-4-phenyl-but-3enylamine (S-6) is a potent dual dopamine/serotonin (DA/5-HT) releaser with no activity at 5-HT2 receptors. This unique profile of actions suggests that analog S-6 is a viable lead compound for identifying new structural classes of DA/5-HT releasers with therapeutic benefit and reduced abuse liability. C1 [Decker, Ann M.; Blough, Bruce E.] RTI Int, Ctr Drug Discovery, 3040 E Cornwallis Rd, Res Triangle Pk, NC 27709 USA. [Partilla, John S.; Baumann, Michael H.; Rothman, Richard B.] NIDA, Med Chem Sect, NIH, Baltimore, MD 21224 USA. [Rothman, Richard B.] MedStar St Marys Hosp, Dept Psychiat, 25500 Point Lookout Rd, Leonardtown, MD 20650 USA. RP Blough, BE (reprint author), RTI Int, Ctr Drug Discovery, 3040 E Cornwallis Rd, Res Triangle Pk, NC 27709 USA. EM beb@rti.org FU National Institute on Drug Abuse Project [DA12970]; Intramural Research Program, National Institute on Drug Abuse, NIH FX This research was supported by the National Institute on Drug Abuse Project DA12970 (BEB) and the Intramural Research Program, National Institute on Drug Abuse, NIH. NR 40 TC 0 Z9 0 U1 1 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 EI 2040-2511 J9 MEDCHEMCOMM JI MedChemComm PY 2016 VL 7 IS 8 BP 1657 EP 1663 DI 10.1039/c6md00245e PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA DT3XA UT WOS:000381413300018 ER PT S AU Coulon, A Larson, DR AF Coulon, A. Larson, D. R. BE Filonov, GS Jaffrey, SR TI Fluctuation Analysis: Dissecting Transcriptional Kinetics with Signal Theory SO VISUALIZING RNA DYNAMICS IN THE CELL SE Methods in Enzymology LA English DT Review; Book Chapter ID FLUORESCENCE CORRELATION SPECTROSCOPY; TIME; VISUALIZATION; DYNAMICS; REVEALS; YEAST AB Recent live-cell microscopy techniques now allow the visualization in multiple colors of RNAs as they are transcribed on genes of interest. Following the number of nascent RNAs over time at a single locus reveals complex fluctuations originating from the underlying transcriptional kinetics. We present here a technique based on concepts from signal theory-called fluctuation analysis-to analyze and interpret multicolor transcriptional time traces and extract the temporal signatures of the underlying mechanisms. The principle is to generate, from the time traces, a set of functions called correlation functions. We explain how to compute these functions practically from a set of experimental traces and how to interpret them through different theoretical and computational means. We also present the major difficulties and pitfalls one might encounter with this technique. This approach is capable of extracting mechanistic information hidden in transcriptional fluctuations at multiple timescales and has broad applications for understanding transcriptional kinetics. C1 [Coulon, A.] PSL Res Univ, Inst Curie, Lab Phys Chim, CNRS UMR 168, Paris, France. [Coulon, A.] Univ Paris 06, Sorbonne Univ, Paris, France. [Larson, D. R.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Coulon, A (reprint author), PSL Res Univ, Inst Curie, Lab Phys Chim, CNRS UMR 168, Paris, France.; Coulon, A (reprint author), Univ Paris 06, Sorbonne Univ, Paris, France. EM antoine.coulon@curie.fr RI Coulon, Antoine/A-9006-2012 NR 23 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-802488-1; 978-0-12-802292-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2016 VL 572 BP 159 EP 191 DI 10.1016/bs.mie.2016.03.017 PG 33 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BF5IG UT WOS:000382016100008 PM 27241754 ER PT S AU Vandergaast, R Fredericksen, BL AF Vandergaast, Rianna Fredericksen, Brenda L. BE Colpitts, TM TI Generating West Nile Virus from an Infectious Clone SO WEST NILE VIRUS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE West Nile virus; Infectious clone; Infectious RNA; Electroporation; In vitro transcription; Two-plasmid system ID CDNA-CLONE; FLAVIVIRUS; STRAIN; CONSTRUCTION; REPLICATION; DESIGN; DNA AB WNV infectious clones are valuable tools for elucidating WNV biology. Nevertheless, relatively few infectious WNV clones have been generated because their construction is hampered by the instability of flaviviral genomes. More recently, advances in cloning techniques as well as the development of several two-plasmid WNV infectious clone systems have facilitated the generation of WNV infectious clones. Here we described a protocol for recovering WNV from a two-plasmid system. In this approach, large quantities of these constructs are digested with restriction enzymes to produce complementary restriction sites at the 3' end of the upstream fragment and the 5' end of the downstream fragment. These fragments are then annealed to produce linear template for in vitro transcription to synthesize infectious RNA. The resulting RNA is transfected into cells and after several days WNV is recovered in the culture supernatant. This method can be used to generate virus from infectious clones encoding high-and low-pathogenicity strains of WNV, as well as chimeric virues. C1 [Vandergaast, Rianna] Imanis Life Sci, Rochester, MN 55902 USA. [Fredericksen, Brenda L.] NIAID, Scientifi c Review Program, Div Extramural Act, NIH,DHHS,AIDS Res Review Branch, Rockville, MD 20857 USA. RP Vandergaast, R (reprint author), Imanis Life Sci, Rochester, MN 55902 USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3670-0; 978-1-4939-3668-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1435 BP 29 EP 43 DI 10.1007/978-1-4939-3670-0_4 D2 10.1007/978-1-4939-3670-0 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Infectious Diseases; Tropical Medicine SC Biochemistry & Molecular Biology; Infectious Diseases; Tropical Medicine GA BF4YJ UT WOS:000381766900005 PM 27188548 ER PT S AU Egli, M White, DA Acri, JB AF Egli, M. White, D. A. Acri, J. B. BE Bell, RL Rahman, S TI Considerations in the Evaluation of Potential Efficacy of Medications for Alcohol and Drug Use Disorders: An Editorial SO ANIMAL MODELS FOR MEDICATIONS SCREENING TO TREAT ADDICTION SE International Review of Neurobiology LA English DT Review; Book Chapter ID RECEPTOR ANTAGONIST NALTREXONE; COCAINE-SEEKING BEHAVIOR; PLACEBO-CONTROLLED TRIAL; ETHANOL DRINKING; RHESUS-MONKEYS; DOUBLE-BLIND; DEPENDENT PATIENTS; PREFERRING RATS; ANIMAL-MODELS; C57BL/6J MICE AB The societal burden created by alcohol and drug use disorders is estimated to be on the order of hundreds of billions of dollars, creating a need for effective medications to reduce use and prevent relapse. While there are FDA-approved medications to facilitate abstinence and prevent relapse for some indications including, alcohol, tobacco, and opiate use disorders, there are no approved treatments for other abused substances, including cocaine, methamphetamine, and cannabis, leaving these critical medical needs unmet. The development of such medications has fallen largely to the government with efforts spearheaded by the National Institute on Drug Abuse and the National Institute on Alcoholism and Alcohol Abuse. Both agencies have medication development programs with preclinical components that include the standardized evaluation of compounds using animal models. This chapter describes the rationale and considerations involved in the use of such models, including reinstatement of drug self-administration. C1 [Egli, M.] NIAAA, NIH, Bethesda, MD USA. [White, D. A.; Acri, J. B.] NIDA, NIH, Bethesda, MD 20892 USA. RP White, DA (reprint author), NIDA, NIH, Bethesda, MD 20892 USA. EM whitedav@nida.nih.gov NR 82 TC 0 Z9 0 U1 4 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-804058-4; 978-0-12-804013-3 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2016 VL 126 BP 1 EP 14 DI 10.1016/bs.irn.2016.02.007 PG 14 WC Substance Abuse; Pharmacology & Pharmacy SC Substance Abuse; Pharmacology & Pharmacy GA BF4SG UT WOS:000381639400002 PM 27055609 ER PT S AU Panlilio, LV Justinova, Z Trigo, JM Le Foll, B AF Panlilio, L. V. Justinova, Z. Trigo, J. M. Le Foll, B. BE Bell, RL Rahman, S TI Screening Medications for the Treatment of Cannabis Use Disorder SO ANIMAL MODELS FOR MEDICATIONS SCREENING TO TREAT ADDICTION SE International Review of Neurobiology LA English DT Review; Book Chapter ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; HEAVY MARIJUANA SMOKERS; ORAL THC MAINTENANCE; DOUBLE-BLIND; SQUIRREL-MONKEYS; DELTA(9)-TETRAHYDROCANNABINOL THC; CB1 RECEPTOR; N-ACETYLCYSTEINE; RHESUS-MONKEYS AB Cannabis use has been increasingly accepted legally and in public opinion. However, cannabis has the potential to produce adverse physical and mental health effects, and cannabis use disorder (CUD) occurs in a substantial percentage of both occasional and daily cannabis users. Many people have difficulty discontinuing use despite receiving treatment. Therefore, it would be beneficial to develop safe and effective medications for treating CUD. To achieve this, methods have been developed for screening and evaluating potential medications using animal models and controlled experimental protocols in human volunteers. In this chapter, we describe: (1) animal models available for assessing the effect of potential medications on specific aspects of CUD, (2) the main findings obtained so far with these animal models, (3) the approaches used to assess potential medications in humans in laboratory experiments and clinical trials, and (4) the effectiveness of several potential pharmacotherapies on particular aspects of CUD modeled in these human studies. C1 [Panlilio, L. V.; Justinova, Z.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, NIH,DHHS, Baltimore, MD USA. [Trigo, J. M.; Le Foll, B.] CAMH, Translat Addict Res Lab, Campbell Family Mental Hlth Res Inst, Toronto, ON, Canada. [Le Foll, B.] Ctr Addict & Mental Hlth, Addict Med Serv Ambulatory Care & Structured Trea, Toronto, ON, Canada. [Le Foll, B.] Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Toronto, ON, Canada. [Le Foll, B.] Univ Toronto, Toronto, ON, Canada. [Le Foll, B.] Univ Toronto, Inst Med Sci, Toronto, ON, Canada. RP Le Foll, B (reprint author), CAMH, Translat Addict Res Lab, Campbell Family Mental Hlth Res Inst, Toronto, ON, Canada.; Le Foll, B (reprint author), Ctr Addict & Mental Hlth, Addict Med Serv Ambulatory Care & Structured Trea, Toronto, ON, Canada.; Le Foll, B (reprint author), Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Toronto, ON, Canada.; Le Foll, B (reprint author), Univ Toronto, Toronto, ON, Canada.; Le Foll, B (reprint author), Univ Toronto, Inst Med Sci, Toronto, ON, Canada. EM bernard.lefoll@camh.ca RI Justinova, Zuzana/A-9109-2011 OI Justinova, Zuzana/0000-0001-5793-7484 FU Intramural NIH HHS [Z99 DA999999] NR 123 TC 0 Z9 0 U1 7 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-804058-4; 978-0-12-804013-3 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2016 VL 126 BP 87 EP 120 DI 10.1016/bs.irn.2016.02.005 PG 34 WC Substance Abuse; Pharmacology & Pharmacy SC Substance Abuse; Pharmacology & Pharmacy GA BF4SG UT WOS:000381639400005 PM 27055612 ER PT S AU Telford, WG AF Telford, William G. BE Muganda, PM TI Measurement of Apoptosis by Multiparametric Flow Cytometry SO APOPTOSIS METHODS IN TOXICOLOGY SE Methods in Pharmacology and Toxicology LA English DT Article; Book Chapter DE Apoptosis measurement; Flow cytometry; Apoptosis assays; Multiparametric; Caspase 3/7 substrate; Caspase 3 immunolabeling; Annexin V; FLICA (fluorescence linked inhibitor of caspase activity); Covalent binding viability probes; DNA binding dyes ID CELL-DEATH; DNA FRAGMENTATION; ACTIVATION; THYMOCYTES; CASPASES; ICE AB Apoptosis remains a critical phenomenon in cell biology, playing a regulatory role in virtually every tissue system. It is particular crucial in the immune system, ranging from immature immune cell development and selection to downregulation of the mature immune response. Apoptosis is a primary mechanism in the action of antitumor drugs, and is thus an important phenomenon in pharmacology, drug discovery, and toxicology. Flow cytometry is the primary technique for measuring apoptosis in suspension cells; many flow cytometry assays have been developed to measure the entire apoptotic process, from the earliest signal transduction events to the late morphological changes in cell size, proteolysis, and DNA degradation. These assays become even more powerful when they can be combined into single multiparametric assays that can document the process of apoptosis in a single tube. The ability of flow cytometry to measure multiple structural and fluorescent characteristics in single cells is uniquely suited to this task. In this methods review, we show how multiple individual assays can be combined in this fashion. Combining early biochemical and late morphological assays together gives a comprehensive and detailed picture of the apoptotic process. C1 [Telford, William G.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Telford, WG (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1557-2153 BN 978-1-4939-3588-8; 978-1-4939-3586-4 J9 METHOD PHARMACOL TOX JI Methods Pharmacol. Toxicol. PY 2016 BP 49 EP 76 DI 10.1007/978-1-4939-3588-8_4 D2 10.1007/978-1-4939-3588-8 PG 28 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BF4TD UT WOS:000381683500005 ER PT J AU Cahan, A Cimino, JJ AF Cahan, Amos Cimino, James J. TI Visual assessment of the similarity between a patient and trial population Is This Clinical Trial Applicable to My Patient? SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Data representation; clinical decision support systems; patient similarity; visual scale ID PRACTICE GUIDELINES; LABORATORY DATA; PRIMARY-CARE; INFORMATION; REPRESENTATION; VISUALIZATION; HEURISTICS; RELEVANT; DISPLAY; RECORDS AB Background: A critical consideration when applying the results of a clinical trial to a particular patient is the degree of similarity of the patient to the trial population. However, similarity assessment rarely is practical in the clinical setting. Here, we explore means to support similarity assessment by clinicians. Methods: A scale chart was developed to represent the distribution of reported clinical and demographic characteristics of clinical trial participant populations. Constructed for an individual patient, the scale chart shows the patient's similarity to the study populations in a graphical manner. A pilot test case was conducted using case vignettes assessed by clinicians. Two pairs of clinical trials were used, each addressing a similar clinical question. Scale charts were manually constructed for each simulated patient. Clinicians were asked to estimate the degree of similarity of each patient to the populations of a pair of trials. Assessors relied on either the scale chart, a summary table (aligning characteristics of 2 trial populations), or original trial reports. Assessment time and between-assessor agreement were compared. Population characteristics considered important by assessors were recorded. Results: Six assessors evaluated 6 cases each. Using a visual scale chart, agreement between physicians was higher and the time required for similarity assessment was comparable Conclusion: We suggest that further research is warranted to explore visual tools facilitating the choice of the most applicable clinical trial to a specific patient. Automating patient and trial population characteristics extraction is key to support this effort. C1 [Cahan, Amos] IBM TJ Watson Res Ctr, Yorktown Hts, NY USA. [Cahan, Amos] Natl Lib Med, Bethesda, MD USA. [Cimino, James J.] Univ Alabama Birmingham, Inst Informat, Birmingham, AL USA. [Cimino, James J.] NIH, Ctr Clin, Inst Informat, Bethesda, MD 20892 USA. RP Cahan, A (reprint author), 1101 Kitchawan Rd Route 134, Yorktown Hts, NY 10598 USA. EM acahan@us.ibm.com FU Research Participation Program for the Centers for Disease Control and Prevention: National Center for Environmental Health, Division of Laboratory Sciences; National Library of Medicine; NIH Clinical Center FX This project was supported in part by an appointment to the Research Participation Program for the Centers for Disease Control and Prevention: National Center for Environmental Health, Division of Laboratory Sciences, administered by the Oak Ridge Institute for Science and Education through an agreement between the Department of Energy and DLS. Dr. Cimino was supported in part by research funds from the National Library of Medicine and the NIH Clinical Center. NR 21 TC 2 Z9 2 U1 1 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2016 VL 7 IS 2 BP 477 EP 488 DI 10.4338/ACI-2015-12-RA-0178 PG 12 WC Medical Informatics SC Medical Informatics GA DS5IN UT WOS:000380815000014 PM 27437055 ER PT J AU Leibrand, CR Price, DK Figg, WD AF Leibrand, Crystal R. Price, Douglas K. Figg, William D. TI Androgen receptor splice variant 7 (AR-V7) and drug efficacy in castration-resistant prostate cancer: Biomarker for treatment selection exclusion or inclusion? SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE Androgen receptor; prostate cancer; splice variants ID ENZALUTAMIDE; EXPRESSION; SENSITIVITY; DOCETAXEL; GENES AB Currently there are no molecular biomarkers used to help guide treatment selection for those patients with castration-resistant prostate cancer. A recent study published in JAMA Oncology (Antonarakis et al.) presents evidence supporting the potential use of androgen receptor splice variant 7 as a biomarker for optimal treatment selection in this population. C1 [Leibrand, Crystal R.; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 19 TC 1 Z9 1 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PY 2016 VL 17 IS 5 BP 467 EP 469 DI 10.1080/15384047.2016.1156274 PG 3 WC Oncology SC Oncology GA DS1OP UT WOS:000380366100001 PM 26985596 ER PT J AU De Buck, M Gouwy, M Wang, JM Van Snick, J Opdenakker, G Struyf, S Van Damme, J AF De Buck, Mieke Gouwy, Mieke Wang, Ji Ming Van Snick, Jacques Opdenakker, Ghislain Struyf, Sofie Van Damme, Jo TI Structure and Expression of Different Serum Amyloid A (SAA) Variants and their Concentration-Dependent Functions During Host Insults SO CURRENT MEDICINAL CHEMISTRY LA English DT Article DE SAA variants; FPR2; TLR2; leukocytes; chemotaxis; cytokines; inflammatory diseases; amyloidosis ID FORMYL PEPTIDE RECEPTOR; C-REACTIVE PROTEIN; NECROSIS-FACTOR-ALPHA; ACUTE-PHASE PROTEINS; HIGH-DENSITY-LIPOPROTEIN; NF-KAPPA-B; PREMATURE CORONARY ATHEROSCLEROSIS; OBSTRUCTIVE PULMONARY-DISEASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; SIGNAL-TRANSDUCTION PATHWAY AB Serum amyloid A (SAA) is, like C-reactive protein (CRP), an acute phase protein and can be used as a diagnostic, prognostic or therapy follow-up marker for many diseases. Increases in serum levels of SAA are triggered by physical insults to the host, including infection, trauma, inflammatory reactions and cancer. The order of magnitude of increase in SAA levels varies considerably, from a 10- to 100-fold during limited inflammatory events to a 1000-fold increase during severe bacterial infections and acute exacerbations of chronic inflammatory diseases. This broad response range is reflected by SAA gene duplications resulting in a cluster encoding several SAA variants and by multiple biological functions of SAA. SAA variants are single-domain proteins with simple structures and few post-translational modifications. SAA1 and SAA2 are inducible by inflammatory cytokines, whereas SAA4 is constitutively produced. We review here the regulated expression of SAA in normal and transformed cells and compare its serum levels in various disease states. At low concentrations (10-100 ng/ml), early in an inflammatory response, SAA induces chemokines or matrix degrading enzymes via Toll-like receptors and functions as an activator and chemoattractant through a G protein-coupled receptor. When an infectious or inflammatory stimulus persists, the liver continues to produce more SAA (>= 1000 ng/ml) to become an antimicrobial agent by functioning as a direct opsonin of bacteria or by interference with virus infection of host cells. Thus, SAA regulates innate and adaptive immunity and this information may help to design better drugs to treat specific diseases. C1 [De Buck, Mieke; Gouwy, Mieke; Struyf, Sofie; Van Damme, Jo] Univ Leuven, KU Leuven, Rega Inst Med Res, Dept Microbiol & Immunol,Lab Mol Immunol, Leuven, Belgium. [Wang, Ji Ming] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Van Snick, Jacques] Ludwig Canc Res, Brussels Branch, Brussels, Belgium. [Van Snick, Jacques] Catholic Univ Louvain, de Duve Inst, Brussels, Belgium. [Opdenakker, Ghislain] Univ Leuven, KU Leuven, Dept Microbiol & Immunol, Rega Inst Med Res,Lab Immunobiol, Leuven, Belgium. RP Van Damme, J (reprint author), Univ Leuven, Dept Microbiol & Immunol, Rega Inst Med Res, Lab Mol Immunol, Minderbroedersstr 10, B-3000 Leuven, Belgium. EM jo.vandamme@kuleuven.be FU Fund for Scientific Research of Flanders (F.W.O.-Vlaanderen); Interuniversity Attraction Poles Program; Concerted Research Actions of the Regional Government of Flanders [G.O.A. 2013/014]; Belgian Science Policy Office (I.A.P. project) [P7/40] FX The authors would like to thank the Fund for Scientific Research of Flanders (F.W.O.-Vlaanderen), the Interuniversity Attraction Poles Program initiated by the Belgian Science Policy Office (I.A.P. project P7/40) and the Concerted Research Actions (G.O.A. 2013/014) of the Regional Government of Flanders for financial support. NR 246 TC 1 Z9 1 U1 4 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 EI 1875-533X J9 CURR MED CHEM JI Curr. Med. Chem. PY 2016 VL 23 IS 17 BP 1725 EP 1755 DI 10.2174/0929867323666160418114600 PG 31 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA DS4XF UT WOS:000380784200003 PM 27087246 ER PT J AU Pike, VW AF Pike, Victor W. TI Considerations in the Development of Reversibly Binding PET Radioligands for Brain Imaging SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE PET; radioligand; molecular imaging; positron-emitter; carbon-11; fluorine-18; efflux transporter; blood-brain barrier ID POSITRON-EMISSION-TOMOGRAPHY; CENTRAL-NERVOUS-SYSTEM; 5-HT1A RECEPTOR RADIOLIGAND; CANNABINOID CB1 RECEPTORS; P-GLYCOPROTEIN EFFLUX; IN-VIVO EVALUATION; PROTEIN 18 KDA; PERIPHERAL BENZODIAZEPINE-RECEPTORS; NICOTINIC ACETYLCHOLINE-RECEPTORS; POSTMORTEM HUMAN BRAIN AB The development of reversibly binding radioligands for imaging brain proteins in vivo, such as enzymes, neurotransmitter transporters, receptors and ion channels, with positron emission tomography (PET) is keenly sought for biomedical studies of neuropsychiatric disorders and for drug discovery and development, but is recognized as being highly challenging at the medicinal chemistry level. This article aims to compile and discuss the main considerations to be taken into account by chemists embarking on programs of radioligand development for PET imaging of brain protein targets. C1 [Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Rm B3C346A,10 Ctr Dr, Bethesda, MD 20892 USA. RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, Rm B3C346A,10 Ctr Dr, Bethesda, MD 20892 USA. EM pikev@mail.nih.gov FU Intramural Research Program of the National Institutes of Health (NIMH) [ZIA MH002793] FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIMH; ZIA MH002793). The author is grateful to Dr. Shuiyu Lu (NIMH) for critical reading of the manuscript. The author is also grateful to numerous coauthors for their contributions to research cited by the author in this article. NR 384 TC 4 Z9 4 U1 6 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 EI 1875-533X J9 CURR MED CHEM JI Curr. Med. Chem. PY 2016 VL 23 IS 18 BP 1818 EP 1869 DI 10.2174/0929867323666160418114826 PG 52 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA DS4XS UT WOS:000380785500002 PM 27087244 ER PT S AU Tatusova, T AF Tatusova, Tatiana BE Carugo, O Eisenhaber, F TI Update on Genomic Databases and Resources at the National Center for Biotechnology Information SO DATA MINING TECHNIQUES FOR THE LIFE SCIENCES SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Bioinformatics; Genome; Genome assembly; Database; Data management system; Sequence analysis ID ESCHERICHIA-COLI K-12; MICROBIAL GENOMES; ARCHIVE; GENERATION; ASSEMBLIES; SEQUENCE; REFSEQ; LONG AB The National Center for Biotechnology Information (NCBI), as a primary public repository of genomic sequence data, collects and maintains enormous amounts of heterogeneous data. Data for genomes, genes, gene expressions, gene variation, gene families, proteins, and protein domains are integrated with the analytical, search, and retrieval resources through the NCBI website, text-based search and retrieval system, provides a fast and easy way to navigate across diverse biological databases. Comparative genome analysis tools lead to further understanding of evolution processes quickening the pace of discovery. Recent technological innovations have ignited an explosion in genome sequencing that has fundamentally changed our understanding of the biology of living organisms. This huge increase in DNA sequence data presents new challenges for the information management system and the visualization tools. New strategies have been designed to bring an order to this genome sequence shockwave and improve the usability of associated data. C1 [Tatusova, Tatiana] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. RP Tatusova, T (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 25 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3572-7; 978-1-4939-3570-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1415 BP 3 EP 30 DI 10.1007/978-1-4939-3572-7_1 D2 10.1007/978-1-4939-3572-7 PG 28 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA BF4TC UT WOS:000381683400002 PM 27115625 ER PT J AU Accordi, ED Xekouki, P Azevedo, B de Alexandre, RB Frasson, C Gantzel, SM Papadakis, GZ Angelousi, A Stratakis, CA Sotomaior, VS Faucz, FR AF Accordi, Elen Dias Xekouki, Paraskevi Azevedo, Bruna de Alexandre, Rodrigo Bertollo Frasson, Carla Gantzel, Siliane Marie Papadakis, Georgios Z. Angelousi, Anna Stratakis, Constantine A. Sotomaior, Vanessa Santos Faucz, Fabio R. TI Familiar Papillary Thyroid Carcinoma in a Large Brazilian Family Is Not Associated with Succinate Dehydrogenase Defects SO EUROPEAN THYROID JOURNAL LA English DT Article DE Succinate dehydrogenase; Mutations; Papillary thyroid cancer; Genetics; Endocrine tumors ID MITOCHONDRIAL COMPLEX-II; GENE-MUTATIONS; CANCER; PARAGANGLIOMA; PHEOCHROMOCYTOMA; GERMLINE; SDHB; VARIANTS; COEXISTENCE; DEFICIENCY AB Background: Thyroid cancer is the most common endocrine gland malignancy. Advances in understanding the genetic basis for thyroid cancer revealed the potential involvement of several genes in the formation of thyroid tumors. Mutations in the gene coding for succinate dehydrogenase subtype B (SDHB) have been implicated in papillary thyroid cancer (PTC). Succinate dehydrogenase (SDH) is a heterotetrameric protein composed of four subunits, SDHA, SDHB, SDHC, and SDHD, and participates in both the electron transport chain and the tricarboxylic acid cycle. The aim of the study was to evaluate the association between variants in the SDHA, SDHB, SDHC, and SDHD genes and familiar PTC in a large Brazilian family. Method: Four patients with PTC, 1 patient with PTC and gastrointestinal stromal tumor (GIST), 1 patient with GIST, and their relatives - several of them with different thyroid problems - from a large Brazilian family were screened for genetic variations of SDHx genes with the use of polymerase chain reaction-single-stranded conformational polymorphism and direct sequencing. Results: Only one rare variation in SDHA was found in some of the family members, but not segregating with the disease. No other genetic variants of these genes were detected in the family members that presented with PTC and/or GIST. Conclusion: Familiar PTC and a GIST were not associated with SDHx mutations; additional genetic defects, yet unknown, may be responsible for the development of tumor. (C) 2016 European Thyroid Association Published by S. Karger AG, Basel C1 [Accordi, Elen Dias; Azevedo, Bruna; de Alexandre, Rodrigo Bertollo; Frasson, Carla; Gantzel, Siliane Marie; Sotomaior, Vanessa Santos; Faucz, Fabio R.] Pontificia Univ Catolica Parana PUCPR, Sch Med EM, Grad Program Hlth Sci PPGCS, Grp Adv Mol Invest NIMA, Curitiba, Parana, Brazil. [Frasson, Carla] Diagnost Amer DASA, Alvaro Ctr Anal & Clin Res, Cascavel, Brazil. [Xekouki, Paraskevi; Angelousi, Anna; Stratakis, Constantine A.; Faucz, Fabio R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, NIH, Bethesda, MD USA. [Xekouki, Paraskevi; Angelousi, Anna; Stratakis, Constantine A.; Faucz, Fabio R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Endocrinol Interinst Training Program, NIH, Bethesda, MD USA. [Papadakis, Georgios Z.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. RP Faucz, FR (reprint author), NICHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, 10 Ctr Dr,Room 1-3216,MSC1103, Bethesda, MD 20892 USA. EM fabio.faucz@nih.gov NR 41 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2235-0640 EI 2235-0802 J9 EUR THYROID J JI Eur. Thyroid J. PY 2016 VL 5 IS 2 BP 94 EP 99 DI 10.1159/000444522 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DT7RX UT WOS:000381685500002 PM 27493882 ER PT J AU Abdullah, A Amin, FA Hanum, F Stoelwinder, J Tanamas, S Wolf, R Wong, E Peeters, A AF Abdullah, Asnawi Amin, Fauzi Ali Hanum, Farida Stoelwinder, Johannes Tanamas, Stephanie Wolf, Rory Wong, Evelyn Peeters, Anna TI Estimating the risk of type-2 diabetes using obese-years in a contemporary population of the Framingham Study SO GLOBAL HEALTH ACTION LA English DT Article DE BMI; obesity; offspring Framingham; obese-years; type-2 diabetes ID MODELING SMOKING HISTORY; BODY-MASS INDEX; MORTALITY; TIME AB Background: We have recently demonstrated that an obese-years construct is a better predictor of the risk of diabetes than the severity of body weight alone. However, these risk estimates were derived from a population cohort study initiated in 1948 that might not apply to the current population. Objective: To validate an obese-years construct in estimating the risk of type-2 diabetes in a more contemporary cohort study. Design: A total of 5,132 participants of the Framingham Offspring Study, initiated in 1972, were followed up for 45 years. Body mass index (BMI) above 29 kg/m(2) was multiplied by the number of years lived with obesity at that BMI to define the number of obese-years. Time- dependent Cox regression was used to explore the association. Results: The risk of type-2 diabetes increased significantly with increase in obese-years. Adjusted hazard ratios increased by 6% (95% CI: 5-7%) per additional 10 points of obese-years. This ratio was observed to be similar in both men and women, but was 4% higher in current smokers than in never/ex-smokers. The Akaike Information Criterion confirmed that the Cox regression model with the obese-years construct was a stronger predictor of the risk of diabetes than a model including either BMI or the duration of obesity alone. Conclusions: In a contemporary cohort population, it was confirmed that the obese-years construct is strongly associated with an increased risk of type-2 diabetes. This suggests that both severity and the duration of obesity should be considered in future estimations of the burden of disease associated with obesity. C1 [Abdullah, Asnawi; Amin, Fauzi Ali; Hanum, Farida] Univ Muhammadiyah Aceh, Fac Publ Hlth, Banda Aceh, Indonesia. [Abdullah, Asnawi; Stoelwinder, Johannes; Wolf, Rory] Monash Univ, Sch Publ Hlth & Prevent Med, Clayton, Vic, Australia. [Tanamas, Stephanie] NIDDK, NIH, Bethesda, MD 20892 USA. [Wong, Evelyn; Peeters, Anna] Deakin Univ, Sch Hlth & Social Dev, Melbourne, Vic, Australia. RP Abdullah, A (reprint author), Univ Muhammadiyah Aceh, Fac Publ Hlth, Banda Aceh, Indonesia. EM Asnawi.Abdullah@fkm.unmuha.ac.id FU Indonesian Danone Institute Foundation through the institutional research grant scheme; NHMRC grant; National Institutes of Health Visiting Fellow Award FX AA is partly supported by the Indonesian Danone Institute Foundation through the institutional research grant scheme. However, the views expressed herein are those of the individual authors, and not necessarily reflect those of the Indonesian Danone Institute Foundation. AP is supported by an NHMRC grant. ST is supported by a National Institutes of Health Visiting Fellow Award. NR 28 TC 1 Z9 1 U1 0 U2 0 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 1654-9880 J9 GLOBAL HEALTH ACTION JI Glob. Health Action PY 2016 VL 9 AR 30421 DI 10.3402/gha.v9.30421 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DS9FX UT WOS:000381089400001 PM 27369220 ER PT J AU Limmathurotsakul, D Golding, N Dance, DAB Messina, JP Pigott, DM Moyes, CL Rolim, DB Bertherat, E Day, NPJ Peacock, SJ Hay, SI AF Limmathurotsakul, Direk Golding, Nick Dance, David A. B. Messina, Jane P. Pigott, David M. Moyes, Catherine L. Rolim, Dionne B. Bertherat, Eric Day, Nicholas P. J. Peacock, Sharon J. Hay, Simon I. TI Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis SO NATURE MICROBIOLOGY LA English DT Article ID NORTHEAST THAILAND; AUSTRALIA; MORTALITY; RISK AB Burkholderia pseudomallei, a highly pathogenic bacterium that causes melioidosis, is commonly found in soil in Southeast Asia and Northern Australia(1,2). Melioidosis can be difficult to diagnose due to its diverse clinical manifestations and the inadequacy of conventional bacterial identification methods(3). The bacterium is intrinsically resistant to a wide range of antimicrobials, and treatment with ineffective antimicrobials may result in case fatality rates (CFRs) exceeding 70%(4,5). The importation of infected animals has, in the past, spread melioidosis to non-endemic areas(6,7). The global distribution of B. pseudomallei and the burden of melioidosis, however, remain poorly understood. Here, we map documented human and animal cases and the presence of environmental B. pseudomallei and combine this in a formal modelling framework(8-10) to estimate the global burden of melioidosis. We estimate there to be 165,000 (95% credible interval 68,000-412,000) human melioidosis cases per year worldwide, from which 89,000 (36,000-227,000) people die. Our estimates suggest that melioidosis is severely underreported in the 45 countries in which it is known to be endemic and that melioidosis is probably endemic in a further 34 countries that have never reported the disease. The large numbers of estimated cases and fatalities emphasize that the disease warrants renewed attention from public health officials and policy makers. C1 [Limmathurotsakul, Direk; Golding, Nick; Pigott, David M.; Moyes, Catherine L.; Hay, Simon I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Limmathurotsakul, Direk; Day, Nicholas P. J.; Peacock, Sharon J.] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok 10400, Thailand. [Limmathurotsakul, Direk] Mahidol Univ, Fac Trop Med, Dept Trop Hyg, Bangkok 10400, Thailand. [Dance, David A. B.] Lao Oxford Mahosot Hosp, Wellcome Trust Res Unit, Viangchan, Laos. [Dance, David A. B.; Day, Nicholas P. J.] Univ Oxford, Ctr Trop Med & Global Hlth, Old Rd Campus, Oxford OX3 7FZ, England. [Messina, Jane P.] Univ Oxford, Dept Zool, South Parks Rd, Oxford OX1 3PS, England. [Rolim, Dionne B.] Univ Fortaleza, BR-60811905 Fortaleza, Ceara, Brazil. [Bertherat, Eric] WHO, Dept Pandem & Epidem Dis, Geneva 27, Switzerland. [Peacock, Sharon J.] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 0QQ, England. [Peacock, Sharon J.] London Sch Hyg & Trop Med, London WC1E 7HT, England. [Hay, Simon I.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA. [Hay, Simon I.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. RP Limmathurotsakul, D (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.; Limmathurotsakul, D (reprint author), Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok 10400, Thailand.; Limmathurotsakul, D (reprint author), Mahidol Univ, Fac Trop Med, Dept Trop Hyg, Bangkok 10400, Thailand. EM direk@tropmedres.ac OI Hay, Simon/0000-0002-0611-7272; Dance, David/0000-0001-9189-7244; Moyes, Catherine/0000-0002-8028-4079 FU Wellcome Trust [101103, 095066]; Bill & Melinda Gates Foundation [OPP1119467, OPP1106023, OPP1093011]; RAPIDD programme of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX The authors thank P. Wannapinij for technical support and N.J. White and K. Schaecher for comments on the final draft. The authors also thank M. Devine for proofreading. This work was funded by the Wellcome Trust (grant no. 101103). S.I.H. is funded by a Senior Research Fellowship from the Wellcome Trust (grant no. 095066) and grants from the Bill & Melinda Gates Foundation (nos. OPP1119467, OPP1106023 and OPP1093011). S.I.H. acknowledges funding support from the RAPIDD programme of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. NR 32 TC 30 Z9 32 U1 8 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND EI 2058-5276 J9 NAT MICROBIOL JI NAT. MICROBIOL PD JAN PY 2016 VL 1 IS 1 AR 15008 DI 10.1038/NMICROBIOL.2015.8 PG 5 WC Microbiology SC Microbiology GA DT6EW UT WOS:000381577400015 PM 27571754 ER PT S AU Riteau, N Gombault, A Couillin, I AF Riteau, Nicolas Gombault, Aurelie Couillin, Isabelle BE DiVirgilio, F Pelegrin, P TI Assessment of Inflammasome Activation by Cytokine and Danger Signal Detection SO NLR PROTEINS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE ELISA; Immunoblot; IL-1 beta; IL-18; HMGB-1; ATP ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; SECRETORY PATHWAY; MECHANISMS; APOPTOSIS AB The evaluation of the inflammasome activation usually addresses the presence of extracellular IL-1 beta and IL-18 or the secretion of danger signal proteins such as HMGB-1 through their quantification using an enzyme-linked immunosorbent assay (ELISA). The ELISA is a routine laboratory technique that uses antibodies and colorimetric changes to identify a substance of interest. ELISA uses a solid-phase enzyme immunoassay to detect the presence of a substance, usually an antigen, in a liquid or wet sample. Using 96 well plates, the ELISA technique enables to quantify the concentration of a single cytokine in multiple samples. However, a limitation of IL-1 beta and IL-18 ELISA is the absence of discrimination between active and non-active form of the proteins, parameter critical, for example, to distinguish the biologically relevant IL-1 beta from its poorly active form pro-IL-1 beta. This issue can be solved using western blots or immunoblots (IB), a common analytical procedure to detect the presence of different proteins in biological samples. Using denaturating conditions, IB allows the visualization of different sizes of the proteins of choice and is a commonly used technique in the inflammasome field to evaluate, for instance, the maturation of pro-IL-1 beta, pro-IL-18, and pro-caspase-1 into mature IL-1 beta, mature IL-18, and mature caspase-1, respectively. Moreover infl ammasome activation may lead to the release of infl ammasome particles outside the cell through caspase-1- or caspase-11-dependent cell death mechanism termed pyroptosis. In this case, NLR, ASC, and caspase-1 components are detectable outside the cell using IB analysis. ELISA and IB can be performed on cell culture supernatant or cell extract and on ex vivo samples from organ homogenates or biological fluids such as serum and plasma or bronchoalveolar lavages. C1 [Riteau, Nicolas] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Gombault, Aurelie; Couillin, Isabelle] Univ Orleans, INEM, CNRS, UMR7355, Orleans, France. RP Riteau, N (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3566-6; 978-1-4939-3564-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1417 BP 63 EP 74 DI 10.1007/978-1-4939-3566-6_3 D2 10.1007/978-1-4939-3566-6 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BF4SC UT WOS:000381638700004 PM 27221481 ER PT J AU Simons-Morton, B Li, KG Ehsani, J Vaca, FE AF Simons-Morton, Bruce Li, Kaigang Ehsani, Johnathon Vaca, Federico E. TI Covariability in three dimensions of teenage driving risk behavior: impaired driving, risky and unsafe driving behavior, and secondary task engagement SO TRAFFIC INJURY PREVENTION LA English DT Article DE young drivers; teenagers; driving while alcohol; drug impaired; risk taking; alcohol; distraction ID INVOLVEMENT; ADOLESCENTS; DRINKING; DRIVERS; NOVICE; CRASH AB Objective: This research examined the extent to which teenagers who engaged in one form of risky driving also engaged in other forms and whether risky driving measures were reciprocally associated over time.Methods: The data were from waves 1, 2, and 3 (W1, W2, and W3) of the NEXT Generation study, with longitudinal assessment of a nationally representative sample starting with 10th graders starting in 2009-2010. Three measures of risky driving were assessed in autoregressive and cross-lagged analyses: driving while alcohol/drug impaired (DWI), Checkpoints Risky Driving Scale (risky and unsafe driving), and secondary task engagement while driving.Results: In adjusted autoregression models, the risk variables demonstrated high levels of stability, with significant associations observed across the 3 waves. However, associations between variables were inconsistent. DWI at W2 was associated with risky and unsafe driving at W3 ( = 0.21, P < .01); risky and unsafe driving at W1 was associated with DWI at W2 ( = 0.20, P < .01); and risky and unsafe driving at W2 is associated with secondary task engagement at W3 ( = 0.19, P < .01). Over time, associations between DWI and secondary task engagement were not significant.Conclusions: Our findings provide modest evidence for the covariability of risky driving, with prospective associations between the Risky Driving Scale and the other measures and reciprocal associations between all 3 variables at some time points. Secondary task engagement, however, appears largely to be an independent measure of risky driving. The findings suggest the importance of implementing interventions that addresses each of these driving risks. C1 [Simons-Morton, Bruce; Ehsani, Johnathon] Natl Inst Child Hlth & Human Dev, Hlth Behav Branch, 6100 Execut Blvd, Bethesda, MD 20892 USA. [Li, Kaigang] Colorado State Univ, Dept Hlth & Exercise Sci, Ft Collins, CO 80523 USA. [Vaca, Federico E.] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT USA. RP Simons-Morton, B (reprint author), Natl Inst Child Hlth & Human Dev, Hlth Behav Branch, 6100 Execut Blvd, Bethesda, MD 20892 USA. EM mortonb@exchange.nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617 FU intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN275201200001] FX This research was supported by the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, contract #HHSN275201200001. NR 22 TC 0 Z9 0 U1 3 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-9588 EI 1538-957X J9 TRAFFIC INJ PREV JI Traffic Inj. Prev. PY 2016 VL 17 IS 5 BP 441 EP 446 DI 10.1080/15389588.2015.1107183 PG 6 WC Public, Environmental & Occupational Health; Transportation SC Public, Environmental & Occupational Health; Transportation GA DS6HM UT WOS:000380882900001 PM 26514232 ER PT J AU Kyritsi, F Price, DK Figg, WD AF Kyritsi, Fiorina Price, Douglas K. Figg, William D. TI YAP controls transcriptional elongation through CKD9 recruitment for proximal pause release: "Hippo-thetical", new therapeutic targets? SO CANCER BIOLOGY & THERAPY LA English DT Article DE Hippo; YAP pathway; mediator complex; tumorigenesis; transcriptional elongation; YAP-bound regulatory elements ID GROWTH; PATHWAY; PROLIFERATION; COACTIVATOR; INITIATION; ENHANCERS; PROMOTER; COMPLEX AB The Hippo-YAP signaling pathway has been established as a crucial regulator of tissue growth and tumorigenesis but the mechanism for transcriptional control remains unclear. In their study, Galli etal. show that YAP/TAZ binding is restricted to a small number of gene enhancers and that YAP/TAZ regulates transcriptional elongation by recruiting the Mediator complex. C1 [Kyritsi, Fiorina; Price, Douglas K.; Figg, William D.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), Rockville Pike, Bethesda, MD USA. EM figgw@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 16 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 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PY 2016 VL 17 IS 6 BP 592 EP 594 DI 10.1080/15384047.2016.1178883 PG 3 WC Oncology SC Oncology GA DS1OQ UT WOS:000380366200002 PM 27149279 ER PT J AU Markossian, S Arnaoutov, A Saba, NS Larionov, V Dasso, M AF Markossian, Sarine Arnaoutov, Alexei Saba, Nakhle S. Larionov, Vladimir Dasso, Mary TI Quantitative assessment of chromosome instability induced through chemical disruption of mitotic progression SO CELL CYCLE LA English DT Article DE aneuploidy; assay development; chromosome instability (CIN); chromosome segregation; human artificial chromosome (HAC) ID HUMAN ARTIFICIAL CHROMOSOMES; CANCER-CELLS; SPINDLE CHECKPOINT; ANEUPLOIDY; IDENTIFICATION; MISSEGREGATION; KINETOCHORE; MECHANISMS; EXPRESSION; CENTROMERE AB Most solid tumors are aneuploid, carrying an abnormal number of chromosomes, and they frequently missegregate whole chromosomes in a phenomenon termed chromosome instability (CIN). While CIN can be provoked through disruption of numerous mitotic pathways, it is not clear which of these mechanisms are most critical, or whether alternative mechanisms could also contribute significantly in vivo. One difficulty in determining the relative importance of candidate CIN regulators has been the lack of a straightforward, quantitative assay for CIN in live human cells: While gross mitotic abnormalities can be detected visually, moderate levels of CIN may not be obvious, and are thus problematic to measure. To address this issue, we have developed the first Human Artificial Chromosome (HAC)-based quantitative live-cell assay for mitotic chromosome segregation in human cells. We have produced U2OS-Phoenix cells carrying the alphoid(tetO)-HAC encoding copies of eGFP fused to the destruction box (DB) of anaphase promoting complex/cyclosome (APC/C) substrate hSecurin and sequences encoding the tetracycline repressor fused to mCherry (TetR-mCherry). Upon HAC missegregation, daughter cells that do not obtain a copy of the HAC are GFP negative in the subsequent interphase. The HAC can also be monitored live following the TetR-mCherry signal. U2OS-Phoenix cells show low inherent levels of CIN, which can be enhanced by agents that target mitotic progression through distinct mechanisms. This assay allows direct detection of CIN induced by clinically important agents without conspicuous mitotic defects, allowing us to score increased levels of CIN that fall below the threshold required for discernable morphological disruption. C1 [Markossian, Sarine; Arnaoutov, Alexei; Dasso, Mary] NICHD, Div Mol & Cellular Biol, NIH, Bldg 18,Rm 106,MSC 5431, Bethesda, MD 20892 USA. [Saba, Nakhle S.] Tulane Univ, Dept Med, Sect Hematol & Med Oncol, New Orleans, LA 70118 USA. [Larionov, Vladimir] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Dasso, M (reprint author), NICHD, Div Mol & Cellular Biol, NIH, Bldg 18,Rm 106,MSC 5431, Bethesda, MD 20892 USA. EM dassom@mail.nih.gov OI Dasso, Mary/0000-0002-5410-1371 FU NICHD [HD008954] FX This work was supported through NICHD Intramural Project HD008954. NR 39 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 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2016 VL 15 IS 13 BP 1706 EP 1714 DI 10.1080/15384101.2016.1175796 PG 9 WC Cell Biology SC Cell Biology GA DR8FA UT WOS:000380132600012 PM 27104376 ER PT J AU de Villiers, TJ Hall, JE Pinkerton, JV Perez, SC Rees, M Yang, C Pierroz, DD AF de Villiers, T. J. Hall, J. E. Pinkerton, J. V. Cerdas Perez, S. Rees, M. Yang, C. Pierroz, D. D. TI Revised Global Consensus Statement on Menopausal Hormone Therapy SO CLIMACTERIC LA English DT Editorial Material ID CLINICAL-PRACTICE GUIDELINE; RECOMMENDATIONS; HEALTH; WOMEN C1 [de Villiers, T. J.] Univ Stellenbosch, Mediclin Panorama, Cape Town, South Africa. [de Villiers, T. J.] Univ Stellenbosch, Dept Gynecol, Cape Town, South Africa. [Hall, J. E.] NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Pinkerton, J. V.] Univ Virginia Hlth Syst, Dept Obstet & Gynecol, Charlottesville, VA USA. [Cerdas Perez, S.] Hosp Cima, Dept Endocrinol, San Jose, Costa Rica. [Rees, M.] Univ Oxford, Oxford OX1 2JD, England. [Yang, C.] Mt Alvernia Hosp, Singapore, Singapore. [Pierroz, D. D.] Univ Geneva, CH-1211 Geneva 4, Switzerland. RP de Villiers, TJ (reprint author), MediClin Panorama, ZA-7500 Parow, South Africa. EM tobie@iafrica.com OI Hall, Janet/0000-0003-4644-3061 NR 6 TC 3 Z9 3 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1369-7137 EI 1473-0804 J9 CLIMACTERIC JI Climacteric PY 2016 VL 19 IS 4 BP 313 EP 315 DI 10.1080/13697137.2016.1196047 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DR9PR UT WOS:000380229100004 PM 27322027 ER PT J AU Sawyer, IA Shevtsov, SP Dundr, M AF Sawyer, Iain A. Shevtsov, Sergei P. Dundr, Miroslav TI Spectral imaging to visualize higher-order genomic organization SO NUCLEUS LA English DT Article DE chromosome territories; Cajal bodies; DNA FISH; genome organization; gene positioning; nuclear bodies; spliceosomal U snRNA genes; spectral imaging ID IN-SITU HYBRIDIZATION; SMALL NUCLEAR-RNA; CAJAL BODIES; COILED BODIES; 3D GENOME; FLUORESCENCE MICROSCOPY; KARYOTYPING HUMAN; GENE-EXPRESSION; CELL-CYCLE; ASSOCIATE AB A concern in the field of genomics is the proper interpretation of large, high-throughput sequencing datasets. The use of DNA FISH followed by high-content microscopy is a valuable tool for validation and contextualization of frequently occurring gene pairing events at the single-cell level identified by deep sequencing. However, these techniques possess certain limitations. Firstly, they do not permit the study of colocalization of many gene loci simultaneously. Secondly, the direct assessment of the relative position of many clustered gene loci within their respective chromosome territories is impossible. Thus, methods are required to advance the study of higher-order nuclear and cellular organization. Here, we describe a multiplexed DNA FISH technique combined with indirect immunofluorescence to study the relative position of 6 distinct genomic or cellular structures. This can be achieved in a single hybridization step using spectral imaging during image acquisition and linear unmixing. Here, we detail the use of this method to quantify gene pairing between highly expressed spliceosomal genes and compare these data to randomly positioned in silico simulated gene clusters. This is a potentially universally applicable approach for the validation of 3C-based technologies, deep imaging of spatial organization within the nucleus and global cellular organization. C1 [Sawyer, Iain A.; Shevtsov, Sergei P.; Dundr, Miroslav] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Cell Biol, 3333 Green Bay Rd, N Chicago, IL 60064 USA. [Sawyer, Iain A.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Dundr, M (reprint author), Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Cell Biol, 3333 Green Bay Rd, N Chicago, IL 60064 USA. EM Mirek.Dundr@rosalindfranklin.edu FU NIH from NIGMS [R01GM090156] FX This work was funded by NIH grant R01GM090156 from NIGMS. NR 57 TC 1 Z9 1 U1 4 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1949-1034 EI 1949-1042 J9 NUCLEUS-PHILA JI Nucleus PY 2016 VL 7 IS 3 BP 325 EP 338 DI 10.1080/19491034.2016.1187344 PG 14 WC Cell Biology SC Cell Biology GA DR9TP UT WOS:000380239300010 PM 27167405 ER PT J AU Robinson, CD Rogers, CR Okuyemi, KS AF Robinson, Cendrine D. Rogers, Charles R. Okuyemi, Kolawole S. TI Depression Symptoms Among Homeless Smokers: Effect of Motivational Interviewing SO SUBSTANCE USE & MISUSE LA English DT Article DE Cessation; depression symptoms; homeless smokers; nicotine; tobacco ID SMOKING-CESSATION; SHELTERED HOMELESS; CLINICAL-TRIAL; DISEASE; RISK; INTERVENTION; ADULTS; PILOT AB Background: Tobacco use is higher among homeless individuals than the general population. Homeless individuals are also more likely to have symptoms of depression. Depression symptoms may add to the burden of homelessness by increasing psychological distress and serve as a barrier to quitting smoking. Objectives: The primary goal of this study is to assess the impact of depression symptoms on psychological distress in homeless smokers. The effect of depression symptoms on abstinence and the effect of Motivational Interviewing (MI) on cessation among smokers is also explored. Methods: Homeless smokers (N = 430) enrolled in a smoking cessation study were randomized to Motivational Interviewing (MI) or standard care (SC). Participants received nicotine replacement therapy and were followed for 26weeks. Participants were categorized into a depression symptoms (DS) group or control group using the Patient Health Questionnaire-9. Between group differences of perceived stress, hopelessness, confidence, craving and abstinence were assessed at weeks 8 and 26. The interaction between depression symptoms (levels: DS and control) and the intervention (levels: MI and SC) was also assessed. Results: Homeless smokers in the DS group reported higher levels of hopelessness, perceived stress, and craving. There was no effect of DS status on abstinence at week 8 or week 26. There was no significant interaction between depression symptoms (DS vs. Control) and the intervention (MI vs. SC). Conclusion: Despite reporting greater psychological distress, homeless smokers with depression symptoms in this sample had abstinence levels similar to the control group. Future research should explore protective factors among depressed smokers. C1 [Robinson, Cendrine D.] Uniformed Serv Univ Heath Sci, Dept Med & Clin Psychol, Bethesda, MD USA. [Rogers, Charles R.; Okuyemi, Kolawole S.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RP Robinson, CD (reprint author), NCI, 9609 Med Ctr Dr, Rockville, MD 20850 USA. EM robinsoncd@mail.nih.gov OI Rogers, Dr. Charles R/0000-0002-3571-8229 FU National Cancer Institute [R25CA16318]; National Heart, Lung, and Blood Institute [R25CA16318, R01HL0815] FX Ths work was supported by the National Cancer Institute [Grant number R25CA16318] and the National Heart, Lung, and Blood Institute [Grant numbers R01HL0815 and R25CA16318]. NR 29 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 1082-6084 EI 1532-2491 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2016 VL 51 IS 10 BP 1393 EP 1397 DI 10.3109/10826084.2016.1170143 PG 5 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA DR8IT UT WOS:000380142300014 PM 27267588 ER PT J AU Jayappa, KD Kovi, RC Chatterjee, S AF Jayappa, Kallesh D. Kovi, Ramesh C. Chatterjee, Sumanta TI Interplay between Tumor Microenvironment and Cancer Cells SO BIOMED RESEARCH INTERNATIONAL LA English DT Editorial Material C1 [Jayappa, Kallesh D.] Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22908 USA. [Kovi, Ramesh C.] NIEHS, Expt Pathol Labs Inc, Res Triangle Pk, NC 27709 USA. [Kovi, Ramesh C.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Chatterjee, Sumanta] Univ Manitoba, Dept Immunol, Winnipeg, MB R3E 0W2, Canada. [Chatterjee, Sumanta] Univ Manitoba, Regenerat Med Program, Winnipeg, MB R3E 0W2, Canada. RP Jayappa, KD (reprint author), Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22908 USA. EM kallesh426@gmail.com OI D. Jayappa, Kallesh/0000-0002-7239-5246 NR 0 TC 0 Z9 0 U1 1 U2 1 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2016 AR 4650498 DI 10.1155/2016/4650498 PG 2 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA DS0TL UT WOS:000380309500001 ER PT J AU Sasso, KE Strunk, DR Braun, JD DeRubeis, RJ Brotman, MA AF Sasso, Katherine E. Strunk, Daniel R. Braun, Justin D. DeRubeis, Robert J. Brotman, Melissa A. TI A re-examination of process-outcome relations in cognitive therapy for depression: Disaggregating within-patient and between-patient effects SO PSYCHOTHERAPY RESEARCH LA English DT Article DE cognitive behavior therapy; depression; alliance; process research; statistical methods ID SYMPTOM CHANGE; ALLIANCE; SESSION; GAINS; MEDICATIONS; ASSESSMENTS; PREDICTORS; DISORDER AB Objective: We previously examined alliance and therapist adherence as predictors of symptom change. Applying a new analytic strategy, we can ensure that any relations identified were not attributable to stable patient characteristics. Method: Participants were 57 depressed cognitive therapy patients. We disaggregated within- and between-patient variation in process measures. Results: Between-patients, variability in adherence to Cognitive Methods and Negotiating/Structuring predicted patients' symptom change. Within-patients, only variability in ratings of adherence to Cognitive Methods predicted next-session symptom change. Conclusions: Relations involving between-patient process variables are potentially attributable to stable patient characteristics. However, the relation of within-patient Cognitive Methods and session-to-session symptom change cannot be attributed to stable characteristics and is consistent with a causal relationship. C1 [Sasso, Katherine E.; Strunk, Daniel R.; Braun, Justin D.] Ohio State Univ, Dept Psychol, Room 185,1835 Neil Ave, Columbus, OH 43210 USA. [DeRubeis, Robert J.] Univ Penn, Dept Psychol, 3815 Walnut St, Philadelphia, PA 19104 USA. [Brotman, Melissa A.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Sasso, KE (reprint author), Ohio State Univ, Dept Psychol, Room 185,1835 Neil Ave, Columbus, OH 43210 USA. EM sasso.9@buckeyemail.osu.edu RI Brotman, Melissa/H-7409-2013 FU National Institute of Mental Health [MH55877, MH55875, MH01697, MH01741] FX The data presented in this article were collected as part of a clinical trial conducted between 1998 and 2003, which was supported by the National Institute of Mental Health under Grants MH55877 (R10), MH55875 (R10), MH01697 (K02), and MH01741 (K24). No authors have relevant conflicts of interest. NR 29 TC 0 Z9 0 U1 2 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1050-3307 EI 1468-4381 J9 PSYCHOTHER RES JI Psychother. Res. PY 2016 VL 26 IS 4 BP 387 EP 398 DI 10.1080/10503307.2015.1026423 PG 12 WC Psychology, Clinical SC Psychology GA DR7BZ UT WOS:000380056300002 PM 25876795 ER PT J AU Kumar, G Patlolla, JMR Madka, V Mohammed, A Li, Q Zhang, YT Biddick, L Singh, A Gillaspy, A Lightfoot, S Steele, VE Kopelovich, L Rao, CV AF Kumar, Gaurav Patlolla, Jagan Mohan R. Madka, Venkateshwar Mohammed, Altaf Li, Qian Zhang, Yuting Biddick, Laura Singh, Anil Gillaspy, Allison Lightfoot, Stanley Steele, Vernon E. Kopelovich, Levy Rao, Chinthalapally V. TI Simultaneous targeting of 5-LOX-COX and ODC block NNK-induced lung adenoma progression to adenocarcinoma in A/J mice SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Lung cancer; chemoprevention; DFMO; licofelone; ornithine decarboxylase; Cox-2 ID INHIBITOR LICOFELONE; PANCREATIC-CANCER; CELL-CARCINOMA; CHEMOPREVENTION; GROWTH; 5-LIPOXYGENASE; POLYAMINES; MOUSE; DIFLUOROMETHYLORNITHINE; PREVENTION AB Lung cancer is the leading cause of cancer deaths worldwide. Targeting complementary pathways will achieve better treatment efficacy than a single agent high-dose strategy that could increase risk of side effects and tumor resistance. To target COX-2, 5-LOX, and ODC simultaneously, we tested the effects of a dual 5-LOX-COX inhibitor, licofelone, and an ODC inhibitor, DFMO, alone and in combination, on NNK-induced lung tumors in female A/J mice. Seven-week-old mice were treated with NNK (10 mu mol/mouse, single dose, i.p.) and randomized to different treatment groups. Three weeks after injection, mice were fed control or experimental diets (DFMO 1500/3000 ppm, licofelone 200/400 ppm, or a low-dose combination of 1500 ppm DFMO and 200 ppm licofelone) for 17 or 34 weeks. Both agents significantly inhibited tumor formation in a dose-dependent manner. As anticipated more adenomas and adenocarcinomas were observed at 17 and 34 weeks, respectively. Importantly, low dose combination of DFMO and licofelone showed more pronounced effects at 17 or 34 weeks in inhibiting the total tumor formation (similar to 60%, p < 0.0001) and adenocarcinoma (similar to 65%, p < 0.0001) compared to individual high dose of DFMO (similar to 44% and 46%, p < 0.0001) and licofelone (similar to 48% and 55%, p < 0.0001). DFMO and combination-treated mice lung tumors exhibited modulated ODC pathway components (Oat, Oaz, SRM, SMS, and SAT, p < 0.05) along with decreased proliferation (PCNA, Cyclin D1 and Cyclin A) and increased expression of p53, p21 and p27 compared to mice fed control diet. Both DFMO and licofelone significantly inhibited tumor inflammatory markers. Our findings suggest that a low-dose combined treatment targeting inflammation and polyamine synthesis may provide effective chemoprevention. C1 [Kumar, Gaurav; Patlolla, Jagan Mohan R.; Madka, Venkateshwar; Mohammed, Altaf; Li, Qian; Zhang, Yuting; Biddick, Laura; Singh, Anil; Lightfoot, Stanley; Rao, Chinthalapally V.] Univ Oklahoma, Hlth Sci Ctr, Dept Med,Hematol Oncol Sect, Stephenson Canc Ctr,Ctr Canc Prevent & Drug Dev, Oklahoma City, OK 73104 USA. [Gillaspy, Allison; Steele, Vernon E.; Kopelovich, Levy] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Rao, CV (reprint author), Univ Oklahoma, Hlth Sci Ctr, Ctr Canc Prevent & Drug Dev,BRC West, Hematol Oncol Sect,Dept Med,Stephenson Canc Ctr, Oklahoma City, OK 73104 USA. EM cv-rao@ouhsc.edu FU [NCI-N01-CN-53300] FX The authors thank the University of Oklahoma Health Sciences Center Rodent Barrier Facility and Ms. Kathy Kyler for valuable suggestions and editorial help. This study was funded by NCI-N01-CN-53300. NR 45 TC 3 Z9 3 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2016 VL 6 IS 5 BP 894 EP + PG 18 WC Oncology SC Oncology GA DQ8GP UT WOS:000379447400002 PM 27293987 ER PT J AU Wong, TCB Rebbert, M Wang, CD Chen, XF Heffer, A Zarelli, VE Dawid, IB Zhao, H AF Wong, Thomas C. B. Rebbert, Martha Wang, Chengdong Chen, Xiongfong Heffer, Alison Zarelli, Valeria E. Dawid, Igor B. Zhao, Hui TI Genes regulated by potassium channel tetramerization domain containing 15 (Kctd 15) in the developing neural crest SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE Neural crest; Kctd 15; DNA microarray; Xenopus; gene regulation; transcription factor AP-2 ID TRANSCRIPTION FACTOR AP-2-BETA; PLATE BORDER; CRANIOFACIAL DEVELOPMENT; VERTEBRATE DEVELOPMENT; HISTONE DEACETYLASE; NEGATIVE REGULATOR; XENOPUS EMBRYOS; FACTOR AP-2; PAX3; EXPRESSION AB Neural crest (NC) development is controlled precisely by a regulatory network with multiple signaling pathways and the involvement of many genes. The integration and coordination of these factors are still incompletely understood. Overexpression of Wnt3a and the BMP antagonist Chordin in animal cap cells from Xenopus blastulae induces a large number of NC specific genes. We previously suggested that Potassium Channel Tetramerization Domain containing 15 (Kctd 15) regulates NC formation by affecting Wnt signaling and the activity of transcription factor AP-2. In order to advance understanding of the function of Kctd 15 during NC development, we performed DNA microarray assays in explants injected with Wnt3a and Chordin, and identified genes that are affected by Kctd 15 overexpression. Among the many genes identified, we chose Duf domain containing protein 1 (ddcp 1), Platelet-Derived Growth Factor Receptor a (pdgfra), Complement factor properdin (cfp), Zinc Finger SWIM-Type Containing 5 (zswim 5), and complement component 3 (C3) to examine their expression by whole mount in situ hybridization. Our work points to a possible role for Kctd 15 in the regulation of NC formation and other steps in embryonic development. C1 [Wong, Thomas C. B.; Wang, Chengdong; Zhao, Hui] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. [Rebbert, Martha; Heffer, Alison; Zarelli, Valeria E.; Dawid, Igor B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Dev Biol, DDB, NIH, Bethesda, MD 20892 USA. [Chen, Xiongfong] NCI, Adv Biomed Comp Ctr, NIH, Frederick, MD 21701 USA. [Zhao, Hui] Chinese Acad Sci, Chinese Univ Hong Kong, Kunming Inst Zool, Joint Lab Bioresources & Mol Res Common Dis, Beijing 100864, Peoples R China. RP Zhao, H (reprint author), Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China.; Dawid, IB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Dev Biol, DDB, NIH, Bethesda, MD 20892 USA. EM idawid@mail.nih.gov; zhaohui@cuhk.edu.hk RI Zhao, Hui/B-8429-2016 FU Research Grants Council of Hong Kong [N_CUHK413/12, CUHK24100414]; Lo Kwee-Seong Biomedical Research Fund (SBS-specific); Intramural Research Program of the National Institute of Child Health and Human Development, NIH FX This work was supported by grants from the Research Grants Council of Hong Kong N_CUHK413/12, CUHK24100414, and Lo Kwee-Seong Biomedical Research Fund (SBS-specific) to H. Z., and by the Intramural Research Program of the National Institute of Child Health and Human Development, NIH. We thank colleagues in our laboratories for helpful discussion on this project. NR 63 TC 0 Z9 0 U1 3 U2 4 PU UNIV BASQUE COUNTRY UPV-EHU PRESS PI BILBAO PA PO BOX 1397, BILBAO, BIZKAIA E-48080, SPAIN SN 0214-6282 EI 1696-3547 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2016 VL 60 IS 4-6 BP 159 EP 166 DI 10.1387/ijdb.160058id PG 8 WC Developmental Biology SC Developmental Biology GA DR5QB UT WOS:000379956400010 PM 27389986 ER PT B AU Flessner, MF AF Flessner, Michael F. BE Ceelen, WP Levine, EA TI Peritoneal drug transport SO INTRAPERITONEAL CANCER THERAPY: PRINCIPLES AND PRACTICE LA English DT Article; Book Chapter ID HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY; INTERSTITIAL FLUID PRESSURE; HUMAN ADENOCARCINOMA LS174T; GYNECOLOGIC-ONCOLOGY-GROUP; RESIDUAL OVARIAN-CANCER; BLOOD-FLOW LIMITATIONS; PHASE-I TRIAL; SURFACE-AREA; DISTRIBUTED MODEL; COLORECTAL-CANCER C1 [Flessner, Michael F.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Flessner, MF (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. NR 179 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4822-6119-6; 978-1-4822-6118-9 PY 2016 BP 41 EP 58 PG 18 WC Oncology SC Oncology GA BF0KO UT WOS:000379001700005 ER PT J AU Mohana, S Ganesan, M Agilan, B Karthikeyan, R Srithar, G Mary, RB Ananthakrishnan, D Velmurugan, D Prasad, NR Ambudkar, SV AF Mohana, S. Ganesan, M. Agilan, B. Karthikeyan, R. Srithar, G. Mary, R. Beaulah Ananthakrishnan, D. Velmurugan, D. Prasad, N. Rajendra Ambudkar, Suresh V. TI Screening dietary flavonoids for the reversal of P-glycoprotein-mediated multidrug resistance in cancer SO MOLECULAR BIOSYSTEMS LA English DT Article ID DRUG TRANSPORTERS; HEALTHY-VOLUNTEERS; ABC TRANSPORTERS; CELL-LINES; BINDING; INHIBITORS; MODULATORS; CHEMOTHERAPY; SUBSTRATE; DOCKING AB P-Glycoprotein (P-gp) serves as a therapeutic target for the development of inhibitors to overcome multidrug resistance in cancer cells. Although various screening procedures have been practiced so far to develop first three generations of P-gp inhibitors, their toxicity and drug interaction profiles are still a matter of concern. To address the above important problem of developing safe and effective P-gp inhibitors, we have made systematic computational and experimental studies on the interaction of natural phytochemicals with human P-gp. Molecular docking and QSAR studies were carried out for 40 dietary phytochemicals in the drug-binding site of the transmembrane domains (TMDs) of P-gp. Dietary flavonoids exhibit better interactions with homology modeled human P-gp. Based on the computational analysis, selected flavonoids were tested for their inhibitory potential against P-gp transport function in drug resistant cell lines using calcein-AM and rhodamine 123 efflux assays. It has been found that quercetin and rutin were the highly desirable flavonoids for the inhibition of P-gp transport function and they significantly reduced resistance in cytotoxicity assays to paclitaxel in P-gp overexpressing MDR cell lines. Hence, quercetin and rutin may be considered as potential chemosensitizing agents to overcome multidrug resistance in cancer. C1 [Mohana, S.; Ganesan, M.; Agilan, B.; Karthikeyan, R.; Srithar, G.; Mary, R. Beaulah; Prasad, N. Rajendra] Annamalai Univ, Dept Biochem & Biotechnol, Annamalainagar 608002, Tamil Nadu, India. [Ananthakrishnan, D.; Velmurugan, D.] Univ Madras, BIF, Guindy Campus, Madras, Tamil Nadu, India. [Velmurugan, D.] Univ Madras, CAS Crystallog & Biophys, Guindy Campus, Madras, Tamil Nadu, India. [Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. RP Prasad, NR (reprint author), Annamalai Univ, Dept Biochem & Biotechnol, Annamalainagar 608002, Tamil Nadu, India. EM drprasadnr@gmail.com; ambudkar@mail.nih.gov FU Department of Science and Technology, New Delhi; DST [SR/SO/BB - 0034]; Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Department of Science and Technology, New Delhi. DST Grant no. SR/SO/BB - 0034 to NRP and SVA was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 55 TC 1 Z9 1 U1 2 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X EI 1742-2051 J9 MOL BIOSYST JI Mol. Biosyst. PY 2016 VL 12 IS 8 BP 2458 EP 2470 DI 10.1039/c6mb00187d PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DR4LM UT WOS:000379873100013 PM 27216424 ER PT J AU Schuck, P AF Schuck, Peter TI Sedimentation coefficient distributions of large particles SO ANALYST LA English DT Article ID GRAVITATIONAL-SWEEP SEDIMENTATION; SIZE-DISTRIBUTION ANALYSIS; WALL CARBON NANOTUBES; ANALYTICAL ULTRACENTRIFUGATION; BOUNDARY ANALYSIS; AMYLOID FIBRILS; VELOCITY DATA; PROTEIN; LENGTH; NANOPARTICLES AB The spatial and temporal evolution of concentration boundaries in sedimentation velocity analytical ultracentrifugation reports on the size distribution of particles with high hydrodynamic resolution. For large particles such as large protein complexes, fibrils, viral particles, or nanoparticles, sedimentation conditions usually allow migration from diffusion to be neglected relative to sedimentation. In this case, the shape of the sedimentation boundaries of polydisperse mixtures relates directly to the underlying size-distributions. Integral and derivative methods for calculating sedimentation coefficient distributions g*(s) of large particles from experimental boundary profiles have been developed previously, and are recapitulated here in a common theoretical framework. This leads to a previously unrecognized relationship between g*(s) and the time-derivative of concentration profiles. Of closed analytical form, it is analogous to the well-known Bridgman relationship for the radial derivative. It provides a quantitative description of the effect of substituting the time-derivative by scan differences with finite time intervals, which appears as a skewed box average of the true distribution. This helps to theoretically clarify the differences between results from time-derivative method and the approach of directly fitting the integral definition of g*(s) to the entirety of experimental boundary data. C1 [Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. RP Schuck, P (reprint author), Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. EM schuckp@mail.nih.gov FU Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 59 TC 0 Z9 0 U1 6 U2 9 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0003-2654 EI 1364-5528 J9 ANALYST JI Analyst PY 2016 VL 141 IS 14 BP 4400 EP 4409 DI 10.1039/c6an00534a PG 10 WC Chemistry, Analytical SC Chemistry GA DR1QH UT WOS:000379679500021 PM 27196374 ER PT J AU Zhang, JH Adikaram, P Pandey, M Genis, A Simonds, WF AF Zhang, Jian-Hua Adikaram, Poorni Pandey, Mritunjay Genis, Allison Simonds, William F. TI Optimization of genome editing through CRISPR-Cas9 engineering SO BIOENGINEERED LA English DT Article DE CRISPR-Cas9; efficiency; genome editing; specificity ID STAPHYLOCOCCUS-AUREUS CAS9; CRISPR/CAS9 SYSTEM; DNA-CLEAVAGE; TARGET SITES; SGRNA DESIGN; KNOCK-IN; NUCLEASES; SEQUENCE; CELLS; RECOGNITION AB CRISPR (Clustered Regularly-Interspaced Short Palindromic Repeats)-Cas9 (CRISPR associated protein 9) has rapidly become the most promising genome editing tool with great potential to revolutionize medicine. Through guidance of a 20 nucleotide RNA (gRNA), CRISPR-Cas9 finds and cuts target protospacer DNA precisely 3 base pairs upstream of a PAM (Protospacer Adjacent Motif). The broken DNA ends are repaired by either NHEJ (Non-Homologous End Joining) resulting in small indels, or by HDR (Homology Directed Repair) for precise gene or nucleotide replacement. Theoretically, CRISPR-Cas9 could be used to modify any genomic sequences, thereby providing a simple, easy, and cost effective means of genome wide gene editing. However, the off-target activity of CRISPR-Cas9 that cuts DNA sites with imperfect matches with gRNA have been of significant concern because clinical applications require 100% accuracy. Additionally, CRISPR-Cas9 has unpredictable efficiency among different DNA target sites and the PAM requirements greatly restrict its genome editing frequency. A large number of efforts have been made to address these impeding issues, but much more is needed to fully realize the medical potential of CRISPR-Cas9. In this article, we summarize the existing problems and current advances of the CRISPR-Cas9 technology and provide perspectives for the ultimate perfection of Cas9-mediated genome editing. C1 [Zhang, Jian-Hua; Adikaram, Poorni; Pandey, Mritunjay; Genis, Allison; Simonds, William F.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, JH; Simonds, WF (reprint author), NIH, Bldg 10 Room 8C-205,10,Ctr Dr MSC 1752, Bethesda, MD 20892 USA. EM jianhuaz@mail.nih.gov; wfs@helix.nih.gov FU Intramural Research Programs of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX This research was supported by the Intramural Research Programs of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 55 TC 1 Z9 2 U1 16 U2 28 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2165-5979 EI 2165-5987 J9 BIOENGINEERED JI Bioengineered PY 2016 VL 7 IS 3 BP 166 EP 174 DI 10.1080/21655979.2016.1189039 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA DR2OK UT WOS:000379743600007 PM 27340770 ER PT B AU Buxton, DB AF Buxton, Denis B. BE VanHerk, A Forcada, J Pastorin, G TI Nanotherapeutics for Cardiovascular, Pulmonary, and Hematologic Diseases SO CONTROLLED RELEASE SYSTEMS: ADVANCES IN NANOBOTTLES AND ACTIVE NANOPARTICLES LA English DT Article; Book Chapter C1 [Buxton, Denis B.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20817 USA. RP Buxton, DB (reprint author), NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20817 USA. EM db225a@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU PAN STANFORD PUBLISHING PTE LTD PI SINGAPORE PA PENTHOUSE LEVEL, SUNTEC TOWER 3, 8 TEMASEK BLVD, SINGAPORE, 038988, SINGAPORE BN 978-9-81-461322-4; 978-9-81-461321-7 PY 2016 BP 385 EP 424 PG 40 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA BF0KT UT WOS:000379006100017 ER PT S AU Jett, DA AF Jett, David A. BE Laskin, JD TI The NIH Countermeasures Against Chemical Threats Program: overview and special challenges SO COUNTERMEASURES AGAINST CHEMICAL THREATS SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE chemical threats; chemical emergencies; therapeutics; NIH CounterACT ID SARIN; ATTACK; EXPOSURE; SINGLE AB Intentional exposures to toxic chemicals can stem from terrorist attacks, such as the release of sarin in the Tokyo subway system in 1995, as well as from toxic industrial accidents that are much more common. Developing effective medical interventions is a critical component of the overall strategy to overcome the challenges of chemical emergencies. These challenges include the rapid and lethal mode of action of many toxic chemicals that require equally fast-acting therapies, the large number of chemicals that are considered threats, and the diverse demographics and vulnerabilities of those who may be affected. In addition, there may be long-term deleterious effects in survivors of a chemical exposure. Several U.S. federal agencies are invested in efforts to improve preparedness and response capabilities during and after chemical emergencies. For example, the National Institutes of Health (NIH) Countermeasures Against Chemical Threats (CounterACT) Program supports investigators who are developing therapeutics to reduce mortality and morbidity from chemical exposures. The program awards grants to individual laboratories and includes contract resource facilities and interagency agreements with Department of Defense laboratories. The range of high-quality research within the NIH CounterACT Program network is discussed. C1 [Jett, David A.] NINDS, NIH, 6001 Execut Blvd,Room 3281, Bethesda, MD 20892 USA. RP Jett, DA (reprint author), NINDS, NIH, NSC, 6001 Execut Blvd,Room 3281, Bethesda, MD 20892 USA. EM jettd@ninds.nih.gov NR 9 TC 1 Z9 2 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2016 VL 1374 BP 5 EP 9 DI 10.1111/nyas.13179 PG 5 WC Toxicology SC Toxicology GA BF0TS UT WOS:000379428500001 PM 27398820 ER PT J AU Simpson, EA Suomi, SJ Paukner, A AF Simpson, Elizabeth A. Suomi, Stephen J. Paukner, Annika TI Evolutionary Relevance and Experience Contribute to Face Discrimination in Infant Macaques (Macaca mulatta) SO JOURNAL OF COGNITION AND DEVELOPMENT LA English DT Article ID OWN-AGE BIAS; RHESUS MACAQUES; NEONATAL IMITATION; 1ST YEAR; RECOGNITION; MONKEYS; PERCEPTION; PREFERENCE; ATTENTION; PATTERNS AB In human children and adults, familiar face types-typically own-age and own-species faces-are discriminated better than other face types; however, human infants do not appear to exhibit an own-age bias but instead better discriminate adult faces, which they see more often. There are two possible explanations for this pattern: Perceptual attunement predicts advantages in discrimination for the most experienced face types. Additionally or alternatively, there may be an experience-independent bias for infants to discriminate own-species faces, an adaptation for evolutionarily relevant faces. These possibilities have not been disentangled in studies thus far, and these studies did not control infants' early experiences with faces. In the present study, we tested these predictions in infant macaques (Macaca mulatta) reared under controlled environments, not exposed to adult conspecifics. We measured new-borns' (15-25 days; n = 27) and 6- to 7-month-olds' (n = 35) discrimination of human and macaque faces at 3 ages-young infants, old infants, and adults-in a visual paired comparison task. We found that 6- to 7-month-olds were the best at discriminating adult macaque faces; however, in the first few seconds of looking, tthey additionally discriminated familiar face types-same-aged peer and adult human faces-thereby highlighting the importance of experience with certain face categories. The present data suggest that macaque infants possess both experience-independent and experientially tuned face biases. In human infants, early face skills may likewise be driven by both experience and evolutionary relevance; future studies should consider both of these factors. C1 [Simpson, Elizabeth A.] Univ Miami, Coral Gables, FL 33124 USA. [Simpson, Elizabeth A.] Univ Parma, I-43100 Parma, Italy. [Simpson, Elizabeth A.; Suomi, Stephen J.; Paukner, Annika] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Simpson, EA (reprint author), Univ Miami, Dept Psychol, 5665 Ponce De Leon Blvd, Coral Gables, FL 33146 USA. EM simpsone@miami.edu FU Division of Intramural Research, NICHD; NICHD [P01HD064653] FX The authors were supported by the Division of Intramural Research, NICHD, and NICHD P01HD064653. NR 66 TC 2 Z9 2 U1 3 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1524-8372 EI 1532-7647 J9 J COGN DEV JI J. Cogn. Dev. PY 2016 VL 17 IS 2 BP 285 EP 299 DI 10.1080/15248372.2015.1048863 PG 15 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA DR0QO UT WOS:000379612200005 PM 27212893 ER PT J AU Burgess, HA Lee, CH Wu, CF AF Burgess, Harold A. Lee, Chi-Hon Wu, Chun-Fang TI Neurogenetics of connectomes: from fly to fish SO JOURNAL OF NEUROGENETICS LA English DT Editorial Material ID MUTANT C1 [Burgess, Harold A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Dev Biol, NIH, Bethesda, MD USA. [Lee, Chi-Hon] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Neurobiol Branch, NIH, Bethesda, MD USA. [Wu, Chun-Fang] Univ Iowa, Dept Biol, Iowa City, IA 52242 USA. RP Lee, CH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Neurobiol Branch, NIH, Bethesda, MD USA. EM leechih@mail.nih.gov NR 11 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0167-7063 EI 1563-5260 J9 J NEUROGENET JI J. Neurogenet. PY 2016 VL 30 IS 2 BP 51 EP 53 DI 10.1080/01677063.2016.1183669 PG 3 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA DQ9RK UT WOS:000379546800001 PM 27309474 ER PT J AU White, BH AF White, Benjamin H. TI What genetic model organisms offer the study of behavior and neural circuits SO JOURNAL OF NEUROGENETICS LA English DT Editorial Material DE Animal psychology; behavioral neurobiology; circuit-mapping; ethology; neuroethology; optogenetics ID LIGHT-SHEET MICROSCOPY; CAENORHABDITIS-ELEGANS; COURTSHIP BEHAVIOR; NERVOUS-SYSTEM; OPTOGENETIC STIMULATION; TARGETED EXPRESSION; DECISION NETWORK; FEAR MEMORY; DROSOPHILA; BRAIN AB The past decade has witnessed the development of powerful, genetically encoded tools for manipulating and monitoring neuronal function in freely moving animals. These tools are most readily deployed in genetic model organisms and efforts to map the circuits that govern behavior have increasingly focused on worms, flies, zebrafish, and mice. The traditional virtues of these animals for genetic studies in terms of small size, short generation times, and ease of animal husbandry in a laboratory setting have facilitated rapid progress, and the neural basis of an increasing number of behaviors is being established at cellular resolution in each of these animals. The depth and breadth of this analysis should soon offer a significantly more comprehensive understanding of how the circuitry underlying behavior is organized in particular animals and promises to help answer long-standing questions that have waited for such a brain-wide perspective on nervous system function. The comprehensive understanding achieved in genetic model animals is thus likely to make them into paradigmatic examples that will serve as touchstones for comparisons to understand how behavior is organized in other animals, including ourselves. C1 [White, Benjamin H.] NIMH, Mol Biol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP White, BH (reprint author), NIMH, Mol Biol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM benjaminwhite@mail.nih.gov NR 78 TC 0 Z9 0 U1 4 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0167-7063 EI 1563-5260 J9 J NEUROGENET JI J. Neurogenet. PY 2016 VL 30 IS 2 BP 54 EP 61 DI 10.1080/01677063.2016.1177049 PG 8 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA DQ9RK UT WOS:000379546800002 PM 27328841 ER PT J AU Luo, JN McQueen, PG Shi, B Lee, CH Ting, CY AF Luo, Jiangnan McQueen, Philip G. Shi, Bo Lee, Chi-Hon Ting, Chun-Yuan TI Wiring dendrites in layers and columns SO JOURNAL OF NEUROGENETICS LA English DT Review DE Circuit assembly; dendrite development; layer and column; synaptic circuits ID DROSOPHILA SENSORY NEURONS; RETINAL GANGLION-CELLS; MOTION DETECTION; PROCESSING PROPERTIES; SECRETORY PATHWAY; SIGNALING PATHWAY; GOLGI OUTPOSTS; AXON GUIDANCE; OPTIC LOBE; WILD-TYPE AB The most striking structure in the nervous system is the complex yet stereotyped morphology of the neuronal dendritic tree. Dendritic morphologies and the connections they make govern information flow and integration in the brain. The fundamental mechanisms that regulate dendritic outgrowth and branching are subjects of extensive study. In this review, we summarize recent advances in the molecular and cellular mechanisms for routing dendrites in layers and columns, prevalent organizational structures in the brain. We highlight how dendritic patterning influences the formation of synaptic circuits. C1 [Luo, Jiangnan; Shi, Bo; Lee, Chi-Hon; Ting, Chun-Yuan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuronal Connect, Cell Biol & Neurobiol Branch, Bethesda, MD USA. [McQueen, Philip G.] NIH, Math & Stat Comp Lab, Off Intramural Res, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. [Shi, Bo] Univ Maryland, Coll Comp Math & Nat Sci, Biol Sci Grad Program, College Pk, MD 20742 USA. RP Ting, CY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuronal Connect, Cell Biol & Neurobiol Branch, NIH,Porter Neurosci Ctr, Bldg 35,Room 1C-1006, Bethesda, MD 20892 USA. EM tingch@mail.nih.gov FU Intramural Research Program of the National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD008913]; Center for Information Technology FX Our research is supported by the Intramural Research Program of the National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant HD008913 to C.-H.L.) and the Center for Information Technology (P.G.M.). NR 95 TC 1 Z9 1 U1 4 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0167-7063 EI 1563-5260 J9 J NEUROGENET JI J. Neurogenet. PY 2016 VL 30 IS 2 BP 69 EP 79 DI 10.3109/01677063.2016.1173038 PG 11 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA DQ9RK UT WOS:000379546800004 PM 27315108 ER PT J AU Horstick, EJ Mueller, T Burgess, HA AF Horstick, Eric J. Mueller, Thomas Burgess, Harold A. TI Motivated state control in larval zebrafish: behavioral paradigms and anatomical substrates SO JOURNAL OF NEUROGENETICS LA English DT Review DE Behavior; motivation; neuromodulator; zebrafish ID LOCOMOTOR-ACTIVITY; NUCLEUS-ACCUMBENS; CIRCADIAN RHYTHMICITY; DOPAMINERGIC-NEURONS; MODULATE AGGRESSION; SEARCHING BEHAVIOR; FORAGING BEHAVIOR; FOOD-DEPRIVATION; SEXUAL-BEHAVIOR; MOTOR BEHAVIOR AB Over the course of each day, animals prioritize different objectives. Immediate goals may reflect fluctuating internal homeostatic demands, prompting individuals to seek out energy supplies or warmth. At other times, the environment may present temporary challenges or opportunities. Homeostatic demands and environmental signals often elicit persistent changes in an animal's behavior to meet needs and challenges over extended periods of time. These changes reflect the underlying motivational state of the animal. The larval zebrafish has been established as an effective genetically tractable vertebrate system to study neural circuits for sensory-motor reflexes. Fewer studies have exploited zebrafish to study brain circuits that control motivated behavior. In part this is because appropriate conceptual frameworks, anatomical knowledge, and behavioral paradigms are not yet well established. This review sketches a general conceptual framework for studying motivated state control in animal models, how this applies to larval zebrafish, and the current knowledge on neuroanatomical substrates for state control in this model. C1 [Horstick, Eric J.; Burgess, Harold A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Dev Biol, Bldg 6B,Room 3B308,6 Ctr Dr, Bethesda, MD 20892 USA. [Mueller, Thomas] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA. RP Burgess, HA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Dev Biol, Bldg 6B,Room 3B308,6 Ctr Dr, Bethesda, MD 20892 USA. EM burgessha@mail.nih.gov FU Intramural Research Program of the Eunice Kennedy Shriver National Institute for Child Health and Human Development; Terry C. Johnson Center for Basic Cancer Research; K-INBRE grant [P20GM103418] FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute for Child Health and Human Development (HB) and the Terry C. Johnson Center for Basic Cancer Research and the K-INBRE grant P20GM103418 (TM). NR 140 TC 1 Z9 1 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0167-7063 EI 1563-5260 J9 J NEUROGENET JI J. Neurogenet. PY 2016 VL 30 IS 2 BP 122 EP 132 DI 10.1080/01677063.2016.1177048 PG 11 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA DQ9RK UT WOS:000379546800009 PM 27293113 ER PT J AU Grenen, EG Ferrer, RA Klein, WMP Han, PKJ AF Grenen, Emily G. Ferrer, Rebecca A. Klein, William M. P. Han, Paul K. J. TI General and specific cancer risk perceptions: how are they related? SO JOURNAL OF RISK RESEARCH LA English DT Article DE cancer; risk perception; cognition ID GENDER AB Understanding how people construe and act upon cancer risk is important for efforts to target risk-increasing health behaviors. Importantly, research participants are often asked to estimate their risk for cancer (in general), which could mask the fact that cancer represents a range of diseases, and that different cancer types can have distinct risk factors. It is unclear whether individuals perceive general cancer risk as being comprised of an aggregation of risk for specific cancer sites, or whether general cancer risk perceptions reflect the specific type of cancer most salient to them. In this study, general cancer risk perceptions were regressed on specific risk perceptions for colon, lung, prostate (men only), and breast (women only), using data from a nationally representative sample. We found that among men and women, all forms of cancer predicted independent variance in estimates of general cancer risk. There were also stronger relationships between general risk perceptions and each specific risk perception than between any two specific risk perceptions, suggesting that individuals differentiate between specific cancers and general cancer risk. These findings offer some confidence that people's estimates of general cancer risk take multiple cancer types into account. C1 [Grenen, Emily G.; Ferrer, Rebecca A.; Klein, William M. P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20892 USA. [Han, Paul K. J.] Maine Med Ctr, Ctr Outcomes Res & Evaluat, Portland, OR USA. RP Grenen, EG (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20892 USA. EM emily.grenen@gmail.com OI Han, Paul/0000-0003-0165-1940 NR 16 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1366-9877 EI 1466-4461 J9 J RISK RES JI J. Risk Res. PY 2016 VL 19 IS 5 BP 602 EP 613 DI 10.1080/13669877.2014.1003321 PG 12 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA DR0SX UT WOS:000379618300003 ER PT J AU Longobardi, E Spataro, P Putnick, DL Bornstein, MH AF Longobardi, Emiddia Spataro, Pietro Putnick, Diane L. Bornstein, Marc H. TI Noun and Verb Production in Maternal and Child Language: Continuity, Stability, and Prediction Across the Second Year of Life SO LANGUAGE LEARNING AND DEVELOPMENT LA English DT Article ID VOCABULARY DEVELOPMENT; YOUNG-CHILDREN; LEXICAL DEVELOPMENT; ITALIAN CHILDREN; DIRECTED SPEECH; INFANTS; INPUT; ACQUISITION; FREQUENCY; ENGLISH AB The present study examined continuity/discontinuity and stability/instability of noun and verb production measures in 30 child-mother dyads observed at 16 and 20 months, and predictive relations with the acquisition of nouns and verbs at 24 months. Children exhibited significant discontinuity and robust stability in the frequency of nouns and verbs between 16 and 20 months (over and above the contribution of maternal measures). By contrast, mothers showed small, but significant, increases in the total number of nouns and the percentages of nouns located in the initial and final utterance positions, together with a decrease in the percentage of verbs located in the initial position. After removing the variance explained by child language, mothers' speech was stable only in the percentages of nouns located in the initial and final utterance positions. Finally, children's production of nouns at 24 months was predicted by the percentages of nouns located in the initial and final positions of maternal utterances at 16 months. Maternal measures at 20 months did not predict children's production of nouns nor for verbs at 24 months. Implications for language acquisition are discussed. C1 [Longobardi, Emiddia] Univ Sapienza Rome, Dept Dynam & Clin Psychol, Via Marsi 78, I-00185 Rome, Italy. [Spataro, Pietro] Univ Sapienza Rome, Dept Psychol, Rome, Italy. [Putnick, Diane L.; Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, NIH, Rockville, MD USA. RP Longobardi, E (reprint author), Univ Sapienza Rome, Dept Dynam & Clin Psychol, Via Marsi 78, I-00185 Rome, Italy. EM emiddia.longobardi@uniroma1.it OI Putnick, Diane/0000-0002-6323-749X NR 53 TC 1 Z9 1 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1547-5441 EI 1547-3341 J9 LANG LEARN DEV JI Lang. Learn. Dev. PY 2016 VL 12 IS 2 BP 183 EP 198 DI 10.1080/15475441.2015.1048339 PG 16 WC Linguistics SC Linguistics GA DQ8YY UT WOS:000379498800005 ER PT B AU Newman, DJ Cragg, GM AF Newman, David J. Cragg, Gordon M. BE Baker, BJ TI The Travails of Clinical Trials with Marine-Sourced Compounds SO MARINE BIOMEDICINE: FROM BEACH TO BEDSIDE LA English DT Article; Book Chapter ID TUNICATE ECTEINASCIDIA-TURBINATA; BRYOSTATIN ANTITUMOR MACROLIDES; NATURAL-PRODUCTS; CARIBBEAN TUNICATE; IN-VITRO; CYTOTOXIC PEPTIDES; HALICHONDRIN-B; DIDEMNIN-B; TRIPEPTIDE HEMIASTERLIN; SECONDARY METABOLITES C1 [Newman, David J.; Cragg, Gordon M.] Frederick Natl Lab Canc Res, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Newman, DJ (reprint author), Frederick Natl Lab Canc Res, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. NR 125 TC 1 Z9 1 U1 3 U2 3 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-8213-2; 978-1-4665-8212-5 PY 2016 BP 439 EP 462 PG 24 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BF0TU UT WOS:000379429200016 ER PT J AU Walitt, B Ceko, M Khatiwada, M Gracely, JL Rayhan, R VanMeter, JW Gracely, RH AF Walitt, Brian Ceko, Marta Khatiwada, Manish Gracely, John L. Rayhan, Rakib VanMeter, John W. Gracely, Richard H. TI Characterizing "fibrofog": Subjective appraisal, objective performance, and task-related brain activity during a working memory task SO NEUROIMAGE-CLINICAL LA English DT Article DE Fibromyalgia; Cognitive dysfunction; Neuroimaging; Cognitive testing ID FIBROMYALGIA IMPACT QUESTIONNAIRE; SELF-REPORT QUESTIONNAIRE; CHRONIC-FATIGUE-SYNDROME; GULF-WAR VETERANS; COGNITIVE DYSFUNCTION; BRIEF PAIN; RHEUMATOID-ARTHRITIS; VALIDATION; INVENTORY; IMPAIRMENT AB The subjective experience of cognitive dysfunction ("fibrofog") is common in fibromyalgia. This study investigated the relation between subjective appraisal of cognitive function, objective cognitive task performance, and brain activity during a cognitive task using functional magnetic resonance imaging (fMRI). Sixteen fibromyalgia patients and 13 healthy pain-free controls completed a battery of questionnaires, including the Multiple Ability Self Report Questionnaire (MASQ), a measure of self-perceived cognitive difficulties. Participants were evaluated for working memory performance using a modified N-back working memory task while undergoing Blood Oxygen Level Dependent (BOLD) fMRI measurements. Fibromyalgia patients and controls did not differ in working memory performance. Subjective appraisal of cognitive function was associated with better performance (accuracy) on the working memory task in healthy controls but not in fibromyalgia patients. In fibromyalgia patients, increased perceived cognitive difficulty was positively correlated with the severity of their symptoms. BOLD response during the working memory task did not differ between the groups. BOLD response correlated with task accuracy in control subjects but not in fibromyalgia patients. Increased subjective cognitive impairment correlated with decreased BOLD response in both groups but in different anatomic regions. In conclusion, "fibrofog" appears to be better characterized by subjective rather than objective impairment. Neurologic correlates of this subjective experience of impairment might be separate from those involved in the performance of cognitive tasks. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. C1 [Walitt, Brian; Ceko, Marta; Gracely, John L.] NCCIH, NIH, Bethesda, MD USA. [Walitt, Brian] MedStar Washington Hosp Ctr, Div Rheumatol, Washington, DC USA. [Khatiwada, Manish; VanMeter, John W.] Georgetown Univ, Med Ctr, Dept Neurol, Ctr Funct & Mol Imaging, Washington, DC 20007 USA. [Rayhan, Rakib] Georgetown Univ, Med Ctr, Dept Med, Div Rheumatol Immunol & Allergy, Washington, DC 20007 USA. [Gracely, Richard H.] Univ N Carolina, Sch Med, Ctr Pain Res & Innovat, Chapel Hill, NC USA. RP Walitt, B (reprint author), 10 Ctr Dr Bldg 10-5-2531, Bethesda, MD 20892 USA. EM Brian.walitt@nih.gov FU American College of Rheumatology Research and Education Foundation; MedStar Health Research Institute; Intramural Research program of the NIH; National Center for Complementary and Integrative Health (NCCIH) FX The authors have no conflicts of interest to report in relation to this manuscript. This manuscript was funded by grants from the American College of Rheumatology Research and Education Foundation and the MedStar Health Research Institute. Infrastructural support was provided by Georgetown Howard Universities Center for Clinical and Translational Science (GHUCCTS). This research was supported (in part) by the Intramural Research program of the NIH, National Center for Complementary and Integrative Health (NCCIH). NR 48 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2016 VL 11 BP 173 EP 180 DI 10.1016/j.nicl.2016.01.021 PG 8 WC Neuroimaging SC Neurosciences & Neurology GA DQ9BD UT WOS:000379504500023 PM 26955513 ER PT J AU Roy, S Carass, A Pacheco, J Bilgel, M Resnick, SM Prince, JL Pham, DL AF Roy, Snehashis Carass, Aaron Pacheco, Jennifer Bilgel, Murat Resnick, Susan M. Prince, Jerry L. Pham, Dzung L. TI Temporal filtering of longitudinal brain magnetic resonance images for consistent segmentation SO NEUROIMAGE-CLINICAL LA English DT Article ID REMITTING MULTIPLE-SCLEROSIS; GRAY-MATTER ATROPHY; ALZHEIMERS-DISEASE; OLDER-ADULTS; CONTRAST SYNTHESIS; MR-IMAGES; DEMENTIA; VOLUME; NORMALIZATION; REGISTRATION AB Longitudinal analysis of magnetic resonance images of the human brain provides knowledge of brain changes during both normal aging as well as the progression of many diseases. Previous longitudinal segmentation methods have either ignored temporal information or have incorporated temporal consistency constraints within the algorithm. In this work, we assume that some anatomical brain changes can be explained by temporal transitions in image intensities. Once the images are aligned in the same space, the intensities of each scan at the same voxel constitute a temporal (or 4D) intensity trend at that voxel. Temporal intensity variations due to noise or other artifacts are corrected by a 4D intensity-based filter that smooths the intensity values where appropriate, while preserving real anatomical changes such as atrophy. Here smoothing refers to removal of sudden changes or discontinuities in intensities. Images processed with the 4D filter can be used as a pre-processing step to any segmentation method. We show that such a longitudinal pre-processing step produces robust and consistent longitudinal segmentation results, even when applying 3D segmentation algorithms. We compare with state-of-the-art 4D segmentation algorithms. Specifically, we experimented on three longitudinal datasets containing 4-12 time-points, and showed that the 4D temporal filter is more robust and has more power in distinguishing between healthy subjects and those with dementia, mild cognitive impairment, as well as different phenotypes of multiple sclerosis. (C) 2016 The Authors. Published by Elsevier Inc. C1 [Roy, Snehashis; Pham, Dzung L.] Henry M Jackson Fdn Adv Mil Med, Ctr Neurosci & Regenerat Med, Bethesda, MD 20817 USA. [Carass, Aaron; Bilgel, Murat; Prince, Jerry L.] Johns Hopkins Univ, Dept Elect & Comp Engn, Image Anal & Commun Lab, Baltimore, MD 21218 USA. [Carass, Aaron] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA. [Pacheco, Jennifer; Bilgel, Murat; Resnick, Susan M.] NIA, Lab Behav Neurosci, Bethesda, MD 20892 USA. RP Roy, S (reprint author), Henry M Jackson Fdn Adv Mil Med, Ctr Neurosci & Regenerat Med, Bethesda, MD 20817 USA. EM snehashis.roy@nih.gov OI Roy, Snehashis/0000-0002-7997-3993; Carass, Aaron/0000-0003-4939-5085 FU Department of Defense in the Center for Neuroscience and Regenerative Medicine; Intramural Research Program of the NIA/NIH; [NIH/NINDS R01NS070906]; [NIH/NIBIB R21EB012765] FX Support for this work included funding from the Department of Defense in the Center for Neuroscience and Regenerative Medicine. This work is supported in part by the Intramural Research Program of the NIA/NIH and the grants NIH/NINDS R01NS070906, NIH/NIBIB R21EB012765. We are grateful to the BLSA participants and neuroimaging staff for their dedication to these studies. NR 62 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2016 VL 11 BP 264 EP 275 DI 10.1016/j.nicl.2016.02.005 PG 12 WC Neuroimaging SC Neurosciences & Neurology GA DQ9BD UT WOS:000379504500030 PM 26958465 ER PT J AU Rajesh, M Cai, L Mukhopadhyay, P Vedantham, S AF Rajesh, Mohanraj Cai, Lu Mukhopadhyay, Partha Vedantham, Srinivasan TI Redox Signaling and Myocardial Cell Death: Molecular Mechanisms and Drug Targets SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Editorial Material C1 [Rajesh, Mohanraj] United Arab Emirates Univ, Coll Med & Hlth Sci, Dept Pharmacol & Therapeut, Al Ain 17666, U Arab Emirates. [Cai, Lu] Univ Louisville, Kosair Childrens Hosp, Res Inst, Louisville, KY 40202 USA. [Cai, Lu] Univ Louisville, Dept Pediat, Dept Radiat Oncol & Pharmacol, Louisville, KY 40202 USA. [Cai, Lu] Univ Louisville, Dept Toxicol, Louisville, KY 40202 USA. [Mukhopadhyay, Partha] NIAAA, Lab Cardiovasc Physiol & Tissue Injury, NIH, Bethesda, MD 20892 USA. [Vedantham, Srinivasan] SASTRA Univ, Sch Chem Biotechnol, Dept Biotechnol, Thanjavur 613401, India. RP Rajesh, M (reprint author), United Arab Emirates Univ, Coll Med & Hlth Sci, Dept Pharmacol & Therapeut, Al Ain 17666, U Arab Emirates. EM rajm@uaeu.ac.ae NR 0 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 1942-0900 EI 1942-0994 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2016 AR 3190753 DI 10.1155/2016/3190753 PG 2 WC Cell Biology SC Cell Biology GA DR5XF UT WOS:000379975000001 ER PT J AU Litten, RZ Wilford, BB Falk, DE Ryan, ML Fertig, JB AF Litten, Raye Z. Wilford, Bonnie B. Falk, Daniel E. Ryan, Megan L. Fertig, Joanne B. TI Potential medications for the treatment of alcohol use disorder: An evaluation of clinical efficacy and safety SO SUBSTANCE ABUSE LA English DT Review DE Alcohol use disorder (AUD); medications development; novel medications; personalized medicine; pharmacotherapy ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; 5-HT3 ANTAGONIST ONDANSETRON; PRELIMINARY DOUBLE-BLIND; CONTROLLED PILOT TRIAL; AS-NEEDED NALMEFENE; DEPENDENT PATIENTS; SEROTONIN TRANSPORTER; TOPIRAMATE TREATMENT; PARTIAL AGONIST AB Alcohol use disorder (AUD), as currently defined in the Diagnostic and Statistical Manual, 5th Edition (DSM-5), is a heterogeneous disorder stemming from a complex interaction of neurobiological, genetic, and environmental factors. As a result of this heterogeneity, there is no one treatment for AUD that will work for everyone. During the past 2 decades, efforts have been made to develop a menu of medications to give patients and clinicians more choices when seeking a therapy that is both effective and which has limited side effects. To date, 3 medications have been approved by the US Food and Drug Administration (FDA) to treat alcohol dependence: disulfiram, naltrexone, and acamprosate. In addition to these approved medications, researchers have identified new therapeutic targets and, as a result, a number of alternative medications are now being evaluated for treatment of AUD in human studies. Although not approved by the FDA for the treatment of AUD, in some cases, these alternative medications are being used off-label by clinicians for this purpose. These potential medications are reviewed here. They include nalmefene, varenicline, gabapentin, topiramate, zonisamide, baclofen, ondansetron, levetiracetam, quetiapine, aripiprazole, and serotonin reuptake inhibitors. The effectiveness of these medications has been mixed-some show good efficacy with side effects that are mild to moderate in intensity; others have mixed or promising results but are awaiting findings from ongoing studies; and still others show poor efficacy, despite promising preliminary results. Medications development remains a high priority. Key initiatives for the National Institute on Alcohol Abuse and Alcoholism (NIAAA) include supporting the discovery and development of more effective and safer medications, advancing the field of personalized medicine, and forging public and private partnerships to investigate new and more effective compounds. C1 [Litten, Raye Z.; Falk, Daniel E.; Ryan, Megan L.; Fertig, Joanne B.] NIAAA, NCIG, Div Medicat Dev, Bethesda, MD USA. [Wilford, Bonnie B.] Coalit Phys Educ Subst Use Disorders COPE, Easton, MD USA. RP Litten, RZ (reprint author), NIAAA, Div Medicat Dev, 5635 Fishers Lane, Bethesda, MD 20892 USA. EM rlitten@mail.nih.gov NR 99 TC 2 Z9 2 U1 10 U2 13 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PY 2016 VL 37 IS 2 BP 286 EP 298 DI 10.1080/08897077.2015.1133472 PG 13 WC Substance Abuse SC Substance Abuse GA DR1WH UT WOS:000379695100005 PM 26928397 ER PT S AU Li, ZZ Fischer, A Li, W Li, GQ AF Li, Zengzhuo Fischer, Andrew Li, Wei Li, Guoqiang BE Brown, TG Cogswell, CJ Wilson, T TI Volumetric retinal fluorescence microscopic imaging with extended depth of field SO THREE-DIMENSIONAL AND MULTIDIMENSIONAL MICROSCOPY: IMAGE ACQUISITION AND PROCESSING XXIII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Three-Dimensional and Multidimensional Microscopy - Image Acquisition and Processing XXIII CY FEB 15-17, 2016 CL San Francisco, CA SP SPIE DE microscopy; 3D imaging; extended depth of field; point spread function; wavefront engineering; passive adaptive optics; eye imaging; fluorescence imaging AB Wavefront-engineered microscope with greatly extended depth of field (EDoF) is designed and demonstrated for volumetric imaging with near-diffraction limited optical performance. A bright field infinity-corrected transmissive/reflective light microscope is built with Kohler illumination. A home-made phase mask is placed in between the objective lens and the tube lens for ease of use. General polynomial function is adopted in the design of the phase plate for robustness and custom merit function is used in Zemax for optimization. The resulting EDoF system achieves an engineered point spread function (PSF) that is much less sensitive to object depth variation than conventional systems and therefore 3D volumetric information can be acquired in a single frame with expanded tolerance of defocus. In Zemax simulation for a setup using 32X objective (NA = 0.6), the EDoF is 20 mu m whereas a conventional one has a DoF of 1.5 mu m, indicating a 13 times increase. In experiment, a 20X objective lens with NA = 0.4 was used and the corresponding phase plate was designed and fabricated. Retinal fluorescence images of the EDoF microscope using passive adaptive optical phase element illustrate a DoF around 100 mu m and it is able to recover the volumetric fluorescence images that are almost identical to in-focus images after post processing. The image obtained from the EDoF microscope is also better in resolution and contrast, and the retinal structure is better defined. Hence, due to its high tolerance of defocus and fine restored image quality, EDoF optical systems have promising potential in consumer portable medical imaging devices where user's ability to achieve focus is not optimal, and other medical imaging equipment where achieving best focus is not a necessary. C1 [Li, Zengzhuo; Li, Guoqiang] Ohio State Univ, Dept Ophthalmol & Visual Sci, Columbus, OH 43212 USA. [Li, Zengzhuo; Li, Guoqiang] Ohio State Univ, Dept Elect & Comp Engn, Columbus, OH 43212 USA. [Fischer, Andrew] Ohio State Univ, Dept Neurosci, Columbus, OH 43212 USA. [Li, Wei] NEI, Bethesda, MD 20892 USA. RP Li, GQ (reprint author), Ohio State Univ, Dept Ophthalmol & Visual Sci, Columbus, OH 43212 USA.; Li, GQ (reprint author), Ohio State Univ, Dept Elect & Comp Engn, Columbus, OH 43212 USA. EM li.3090@osu.edu NR 5 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-947-4 J9 PROC SPIE PY 2016 VL 9713 AR 97131C DI 10.1117/12.2213813 PG 7 WC Microscopy; Optics SC Microscopy; Optics GA BF0RU UT WOS:000379357200039 ER PT J AU Dobre, M Roy, J Tao, KX Anderson, AH Bansal, N Chen, J Deo, R Drawz, P Feldman, HI Hamm, LL Hostetter, T Kusek, JW Lora, C Ojo, AO Shrama, K Rahman, M AF Dobre, Mirela Roy, Jason Tao, Kaixiang Anderson, Amanda H. Bansal, Nisha Chen, Jing Deo, Rajat Drawz, Paul Feldman, Harold I. Hamm, L. Lee Hostetter, Thomas Kusek, John W. Lora, Claudia Ojo, Akinlolu O. Shrama, Kumar Rahman, Mahboob CA CRIC Study Investigators TI Serum Bicarbonate and Structural and Functional Cardiac Abnormalities in Chronic Kidney Disease - A Report from the Chronic Renal Insufficiency Cohort Study SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Serum bicarbonate; Left ventricular hypertrophy; Left ventricular geometry; Chronic kidney disease ID LEFT-VENTRICULAR MASS; CARDIOVASCULAR MAGNETIC-RESONANCE; BASE-LINE CHARACTERISTICS; METABOLIC-ACIDOSIS; HEART-FAILURE; 2-DIMENSIONAL ECHOCARDIOGRAPHY; ASSOCIATION; CKD; OUTCOMES; PLASMA AB Background: Heart failure (HF) is a frequent occurrence in chronic kidney disease (CKD) patients and predicts poor survival. Serum bicarbonate is associated with increased rates of HF in CKD; however, the mechanisms leading to this association are incompletely understood. This study aims to assess whether serum bicarbonate is independently associated with structural and functional cardiac abnormalities in CKD. Methods: The association between serum bicarbonate and left ventricular (LV) hypertrophy (LVH), LV mass indexed to height(2.7), LV geometry, ejection fraction (EF) and diastolic dysfunction was assessed in 3,483 participants without NYHA class III/IV HF, enrolled in the Chronic Renal Insufficiency Cohort study. Results: The mean estimated glomerular filtration rate was 42.5 ? 17 ml/min/1.73 m(2). The overall prevalence of LVH was 51.2%, with 57.8, 50.9 and 47.7% for bicarbonate categories < 22, 22-26 and > 26 mmol/l, respectively. Participants with low bicarbonate were more likely to have LVH and abnormal LV geometry (OR 1.32; 95% CI 1.07-1.64, and OR 1.57; 95% CI 1.14-2.16, respectively). However, the association was not statistically significant after adjustment for demographics, traditional cardiovascular risk factors, medications and kidney function (OR 1.07; 95% CI 0.66-1.72, and OR 1.27; 95% CI 0.64-2.51, respectively). No association was found between bicarbonate and systolic or diastolic dysfunction. During follow-up, no significant changes in LV mass or EF were observed in any bicarbonate strata. Conclusions: In a large CKD study, serum bicarbonate was associated with LV mass and concentric LVH; however, this association was attenuated after adjustment for clinical factors suggesting that the observed cardiac effects are mediated through yet unknown mechanisms. (C) 2016 Published by S. Karger AG, Basel C1 [Dobre, Mirela; Hostetter, Thomas; Rahman, Mahboob] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Div Nephrol & Hypertens, 11100 Euclid Ave, Cleveland, OH 44106 USA. [Rahman, Mahboob] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH 44106 USA. [Roy, Jason; Tao, Kaixiang; Anderson, Amanda H.; Feldman, Harold I.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Deo, Rajat] Univ Penn, Perelman Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Bansal, Nisha] Univ Washington, Kidney Res Inst, Div Nephrol, Seattle, WA 98195 USA. [Chen, Jing] Tulane Univ, Sch Med, Dept Med, Sect Nephrol & Hypertens, New Orleans, LA 70112 USA. [Drawz, Paul] Univ Minnesota, Div Renal Dis & Hypertens, Minneapolis, MN 55455 USA. [Kusek, John W.] NIDDK, NIH, Bethesda, MD 20892 USA. [Lora, Claudia] Univ Illinois, Dept Med, Div Nephrol, Chicago, IL USA. [Ojo, Akinlolu O.] Univ Michigan, Dept Med Nephrol, Ann Arbor, MI 48109 USA. [Shrama, Kumar] Univ Calif San Diego, Ctr Renal Translat Med, Div Nephrol Hypertens, San Diego, CA 92103 USA. RP Dobre, M (reprint author), Case Western Reserve Univ, Univ Hosp Case Med Ctr, Div Nephrol & Hypertens, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM Mirela.Dobre@uhhospitals.org FU NIDDK [U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, U01DK060902]; University of Pennsylvania Clinical and Translational Science Award National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) [UL1TR000003]; Johns Hopkins University [UL1 TR-000424]; University of Maryland [GCRC M01 RR-16500]; Clinical and Translational Science Collaborative of Cleveland; NCATS component of the NIH [UL1TR000439]; NIH roadmap for Medical Research; Michigan Institute for Clinical and Health Research [UL1TR000433]; University of Illinois at Chicago [CTSA UL1RR029879]; Tulane University Translational Research in Hypertension and Renal Biology [P30GM103337]; Kaiser Permanente NIH/NCRR UCSF-CTSI [UL1 RR-024131]; [13FTF15920005]; [DK094352-01] FX Funding for the CRIC study was obtained under a cooperative agreement from NIDDK (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported in part by: University of Pennsylvania Clinical and Translational Science Award National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) UL1TR000003, Johns Hopkins University UL1 TR-000424, University of Maryland GCRC M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the NCATS component of the NIH and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research UL1TR000433, University of Illinois at Chicago CTSA UL1RR029879, Tulane University Translational Research in Hypertension and Renal Biology P30GM103337, Kaiser Permanente NIH/NCRR UCSF-CTSI UL1 RR-024131. M.D. is supported by 13FTF15920005. K.S. is supported by DK094352-01. NR 46 TC 1 Z9 2 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2016 VL 43 IS 6 BP 411 EP 420 DI 10.1159/000446860 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA DQ4HU UT WOS:000379165600004 PM 27241893 ER PT J AU Kobrinsky, E Soldatov, NM AF Kobrinsky, Evgeny Soldatov, Nikolai M. TI Electrophysiological evidences of interaction between calcium channels and PA of anthrax SO CHANNELS LA English DT Letter DE anthrax; calcium channel; Cav1.2; gabapentin; patch clamp; protective antigen ID TOXIN; CELLS; IDENTIFICATION; RECEPTOR; SUBUNIT C1 [Kobrinsky, Evgeny; Soldatov, Nikolai M.] NIA, NIH, Baltimore, MD 21224 USA. RP Soldatov, NM (reprint author), Humgenex, 3105 Starner Court, Kensington, MD USA. EM soldatovn.humgenex@verizon.net NR 13 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 1933-6950 EI 1933-6969 J9 CHANNELS JI Channels PY 2016 VL 10 IS 4 BP 253 EP 255 DI 10.1080/19336950.2016.1172886 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DQ5QZ UT WOS:000379261200001 PM 27045324 ER PT J AU Ahuja, M Park, S Shin, DM Muallem, S AF Ahuja, Malini Park, Soonhong Shin, Dong Min Muallem, Shmuel TI TRPML1 as lysosomal fusion guard SO CHANNELS LA English DT Editorial Material DE channel; lysosomes; regulated exocytosis; runaway; TRPML1 C1 [Ahuja, Malini; Muallem, Shmuel] Natl Inst Dent & Craniofacial Res, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. [Park, Soonhong; Shin, Dong Min] Yonsei Univ, Coll Dent, Dept Oral Biol, BK PLUS Project 21, Seoul, South Korea. RP Muallem, S (reprint author), Natl Inst Dent & Craniofacial Res, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.; Shin, DM (reprint author), Yonsei Univ, Coll Dent, Dept Oral Biol, BK PLUS Project 21, Seoul, South Korea. EM dmshin@yuhs.ac; shmuel.muallem@nih.gov NR 8 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 1933-6950 EI 1933-6969 J9 CHANNELS JI Channels PY 2016 VL 10 IS 4 BP 261 EP 263 DI 10.1080/19336950.2016.1169744 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DQ5QZ UT WOS:000379261200004 PM 27028119 ER PT J AU Moss, JL Gilkey, MB Rimer, BK Brewer, NT AF Moss, Jennifer L. Gilkey, Melissa B. Rimer, Barbara K. Brewer, Noel T. TI Disparities in collaborative patient-provider communication about human papillomavirus (HPV) vaccination SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Article DE Collaboration; health inequities; human papillomavirus (HPV) vaccination; patient-provider communication ID SHARED DECISION-MAKING; HEALTH SUPERVISION VISITS; CERVICAL-CANCER INCIDENCE; UNITED-STATES; ADOLESCENT FEMALES; COVERAGE; MODEL; INITIATION; MORTALITY; WOMEN AB Background. Healthcare providers may vary their communications with different patients, which could give rise to differences in vaccination coverage. We examined demographic disparities in parental report of collaborative provider communication and implications for human papillomavirus (HPV) vaccination. Methods. Participants were 4,124 parents who completed the National Immunization Survey-Teen about daughters ages 13-17. We analyzed disparities in collaborative communication (mutual information exchange, deliberation, and decision) and whether they mediated the relationship between demographic characteristics and HPV vaccine initiation. Results. Half of parents (53%) in the survey reported collaborative communication. Poor, less educated, Spanish-speaking, Southern, and rural parents, and parents of non-privately insured and Hispanic adolescents, were least likely to report collaborative communication (all p<.05). These disparities in communication accounted for geographic variation in HPV vaccination, specifically, the higher rates of uptake in the Northeast versus the South (mediation z=2.31, p<.01) and in urban/suburban vs. rural areas (mediation z=2.87, p<.01). These disparities were also associated with vaccination among subgroups with relatively high coverage, minimizing what could have been even higher uptake among Hispanic compared to non-Hispanic white adolescents (mediation z=-3.04, p<.01) and non-privately versus privately insured adolescents (mediation z=-3.67, p<.001). Controlling for provider recommendation attenuated some of these associations (but all p<.10). Conclusions. Collaborative communication showed widespread disparities, being least common among underserved groups. Collaborative communication helped account for differencesand lack of differencesin HPV vaccination among some subgroups of adolescent girls. Leveraging patient-provider communication, especially for underserved demographic groups, could improve HPV vaccination coverage. C1 [Moss, Jennifer L.; Rimer, Barbara K.; Brewer, Noel T.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Behav, Chapel Hill, NC USA. [Moss, Jennifer L.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E514,MSC 9765, Bethesda, MD 20892 USA. [Gilkey, Melissa B.] Harvard Med Sch, Boston, MA USA. [Gilkey, Melissa B.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Rimer, Barbara K.; Brewer, Noel T.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. RP Moss, JL (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E514,MSC 9765, Bethesda, MD 20892 USA. EM jlmoss@email.unc.edu OI Moss, Jennifer/0000-0002-3794-1344 FU National Cancer Institute [F31 CA189411]; [K22 CA186979] FX This research was supported by a grant from the National Cancer Institute (F31 CA189411; PI: Moss). In addition, MBG was supported by K22 CA186979. NR 43 TC 1 Z9 1 U1 2 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PY 2016 VL 12 IS 6 SI SI BP 1476 EP 1483 DI 10.1080/21645515.2015.1128601 PG 8 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA DQ5QH UT WOS:000379259400031 PM 26786888 ER PT J AU Wekesa, C Asiki, G Kasamba, I Waswa, L Reynolds, SJ Nsubuga, RN Newton, R Kamali, A AF Wekesa, Clara Asiki, Gershim Kasamba, Ivan Waswa, Laban Reynolds, Steven J. Nsubuga, Rebecca N. Newton, Rob Kamali, Anatoli TI Atherogenic Risk Assessment among Persons Living in Rural Uganda SO JOURNAL OF TROPICAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; CARDIOVASCULAR RISK; MYOCARDIAL-INFARCTION; DENSITY-LIPOPROTEIN; SERUM-CHOLESTEROL; HDL-CHOLESTEROL; BLOOD-PRESSURE; WOMEN; TRIGLYCERIDES; HYPERTENSION AB Background. Hypertension and dyslipidemia are independent risk factors for coronary heart disease and commonly coexist. Cardiovascular risk can be reliably predicted using lipid ratios such as the atherogenic index, a useful prognostic parameter for guiding timely interventions. Objective. We assessed the cardiovascular risk profile based on the atherogenic index of residents within a rural Ugandan cohort. Methods. In 2011, a population based survey was conducted among 7507 participants. Sociodemographic characteristics, physical measurements (blood pressure, weight, height, and waist and hip circumference), and blood sampling for nonfasting lipid profile were collected for each participant. Atherogenic risk profile, defined as logarithm base ten of (triglyceride divided by high density lipoprotein cholesterol), was categorised as low risk (<0.1), intermediate risk (0.1-0.24), and high risk (>0.24). Results. Fifty-five percent of participants were female and the mean age was 49.9 years (SD +/- 20.2). Forty-two percent of participants had high and intermediate atherogenic risk. Persons with hypertension, untreated HIV infection, abnormal glycaemia, and obesity and living in less urbanised villages were more at risk. Conclusion. A significant proportion of persons in this rural population are at risk of atherosclerosis. Key identified populations at risk should be considered for future intervention against cardiovascular related morbidity and mortality. The study however used parameters from unfasted samples that may have a bearing on observed results. C1 [Wekesa, Clara; Asiki, Gershim; Kasamba, Ivan; Waswa, Laban; Nsubuga, Rebecca N.; Newton, Rob; Kamali, Anatoli] MRC, Uganda Virus Res Inst Uganda Res Unit AIDS, Entebbe, Uganda. [Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Reynolds, Steven J.] Johns Hopkins Sch Med, Baltimore, MD 21205 USA. RP Wekesa, C (reprint author), MRC, Uganda Virus Res Inst Uganda Res Unit AIDS, Entebbe, Uganda. EM clara.wekesa@gmail.com NR 36 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 1687-9686 EI 1687-9694 J9 J TROP MED JI J. Trop. Med. PY 2016 AR 7073894 DI 10.1155/2016/7073894 PG 8 WC Tropical Medicine SC Tropical Medicine GA DQ4VB UT WOS:000379200800001 ER PT J AU Conforto, A Sterr, A Plow, E Cohen, L AF Conforto, Adriana Sterr, Annette Plow, Ela Cohen, Leonardo TI Interventions to Enhance Adaptive Plasticity after Stroke: From Mechanisms to Therapeutic Perspectives SO NEURAL PLASTICITY LA English DT Editorial Material C1 [Conforto, Adriana] Univ Sao Paulo, Hosp Clin, Dept Neurol, Neurol Clin Div, BR-05508090 Sao Paulo, SP, Brazil. [Conforto, Adriana] Hosp Israelita Albert Einstein, BR-05652900 Sao Paulo, SP, Brazil. [Sterr, Annette] Univ Surrey, Dept Psychol, Guildford GU2 7XH, Surrey, England. [Plow, Ela] Cleveland Clin Fdn, Cleveland Clin, Neurol Inst, Ctr Neurol Restorat,Neurosurg, Cleveland, OH 44195 USA. [Cohen, Leonardo] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA. RP Conforto, A (reprint author), Univ Sao Paulo, Hosp Clin, Dept Neurol, Neurol Clin Div, BR-05508090 Sao Paulo, SP, Brazil.; Conforto, A (reprint author), Hosp Israelita Albert Einstein, BR-05652900 Sao Paulo, SP, Brazil. EM adriana.conforto@gmail.com OI Conforto, Adriana/0000-0001-7869-3490 NR 0 TC 0 Z9 0 U1 2 U2 2 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2016 AR 9153501 DI 10.1155/2016/9153501 PG 2 WC Neurosciences SC Neurosciences & Neurology GA DQ4KV UT WOS:000379173700001 ER PT J AU Bu, LL Yu, GT Deng, WW Mao, L Liu, JF Ma, SR Fan, TF Hall, B Kulkarni, AB Zhang, WF Sun, ZJ AF Bu, Lin-Lin Yu, Guang-Tao Deng, Wei-Wei Mao, Liang Liu, Jian-Feng Ma, Si-Rui Fan, Teng-Fei Hall, Bradford Kulkarni, Ashok B. Zhang, Wen-Feng Sun, Zhi-Jun TI Targeting STAT3 signaling reduces immunosuppressive myeloid cells in head and neck squamous cell carcinoma SO ONCOIMMUNOLOGY LA English DT Article DE Head and neck squamous cell carcinoma; myeloid-derived suppressor cells; STAT3; tumor-associated macrophages ID ANTITUMOR IMMUNE-RESPONSE; DENDRITIC CELLS; MOUSE MODEL; TGF-BETA; CANCER; INHIBITION; DIFFERENTIATION; MACROPHAGES; OPPORTUNITIES; INFLAMMATION AB Cumulative evidence suggests that constitutively activated signal transducer and activator of transcription (STAT3) may contribute to sustaining immunosuppressive status, and that inhibiting STAT3 signaling represents a potential strategy to improve antitumor immunity. In the present study, we observed that high levels phosphorylated of STAT3 are significantly associated with the markers for both myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in human head and neck squamous cell carcinoma (HNSCC). Additionally, we showed that targeting STAT3 signaling with a tolerable selective inhibitor S3I-201 significantly decreased immature myeloid cells such as MDSCs, TAMs and iDCs in genetically defined mice HNSCC model. These findings highlight that targeting STAT3 signaling may be effective to enhance antitumor immunity via myeloid suppressor cells in HNSCC. C1 [Bu, Lin-Lin; Yu, Guang-Tao; Deng, Wei-Wei; Mao, Liang; Liu, Jian-Feng; Ma, Si-Rui; Fan, Teng-Fei; Zhang, Wen-Feng; Sun, Zhi-Jun] Minist Educ, State Key Lab Breeding Base Basic Sci Stomatol, Wuhan, Peoples R China. [Bu, Lin-Lin; Yu, Guang-Tao; Deng, Wei-Wei; Mao, Liang; Liu, Jian-Feng; Ma, Si-Rui; Fan, Teng-Fei; Zhang, Wen-Feng; Sun, Zhi-Jun] Minist Educ, Key Lab Oral Biomed, Wuhan, Peoples R China. [Bu, Lin-Lin; Zhang, Wen-Feng; Sun, Zhi-Jun] Wuhan Univ, Sch & Hosp Stomatol, Dept Oral Maxillofacial Head Neck Oncol, Wuhan, Peoples R China. [Hall, Bradford; Kulkarni, Ashok B.; Sun, Zhi-Jun] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. RP Sun, ZJ (reprint author), Minist Educ, State Key Lab Breeding Base Basic Sci Stomatol, Wuhan, Peoples R China.; Sun, ZJ (reprint author), Minist Educ, Key Lab Oral Biomed, Wuhan, Peoples R China.; Sun, ZJ (reprint author), Wuhan Univ, Sch & Hosp Stomatol, Dept Oral Maxillofacial Head Neck Oncol, Wuhan, Peoples R China.; Sun, ZJ (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. EM zhijundejia@163.com FU National Natural Science Foundation of China [81272963, 81472528, 81272964, 81472529]; Divison of Intramural Research, NIDCR, NIH, USA; program for new century excellent talents in university, Ministry of Education of China [NCET-13-0439] FX This research was supported by National Natural Science Foundation of China 81272963, 81472528 (Z.J S.), 81272964, 81472529 (W.F.Z), and the Divison of Intramural Research, NIDCR, NIH, USA (A.B.K.). Z.J.S. was supported by program for new century excellent talents in university (NCET-13-0439), Ministry of Education of China. NR 44 TC 1 Z9 1 U1 6 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 5 AR e1130206 DI 10.1080/2162402X.2015.1130206 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA DQ4GN UT WOS:000379162200039 PM 27467947 ER PT J AU Mensali, N Ying, F Sheng, VOY Yang, WW Walseng, E Kumari, S Fallang, LE Kolstad, A Uckert, W Malmberg, KJ Walchli, S Olweus, J AF Mensali, Nadia Ying, Fan Sheng, Vincent Oei Yi Yang, Weiwen Walseng, Even Kumari, Shraddha Fallang, Lars-Egil Kolstad, Arne Uckert, Wolfgang Malmberg, Karl Johan Walchli, Sebastien Olweus, Johanna TI Targeting B-cell neoplasia with T-cell receptors recognizing a CD20-derived peptide on patient-specific HLA SO ONCOIMMUNOLOGY LA English DT Article DE B-cell malignancies; CD20; gene therapy; haploidentical allogeneic stem cell transplantation; immunotherapy; T-cell receptor ID CHIMERIC-ANTIGEN-RECEPTOR; ENHANCED ANTITUMOR-ACTIVITY; TCR GENE-THERAPY; HIGH-AVIDITY; FOLLICULAR LYMPHOMA; IN-VIVO; POSTTRANSPLANTATION CYCLOPHOSPHAMIDE; ADOPTIVE IMMUNOTHERAPY; CANCER REGRESSION; HUMAN-LYMPHOCYTES AB T cells engineered to express chimeric antigen receptors (CARs) targeted to CD19 are effective in treatment of B-lymphoid malignancies. However, CARs recognize all CD19 positive (pos) cells, and durable responses are linked to profound depletion of normal B cells. Here, we designed a strategy to specifically target patient B cells by utilizing the fact that T-cell receptors (TCRs), in contrast to CARs, are restricted by HLA. Two TCRs recognizing a peptide from CD20 (SLFLGILSV) in the context of foreign HLA-A*02:01 (CD20p/HLA-A2) were expressed as 2A-bicistronic constructs. T cells re-directed with the A23 and A94 TCR constructs efficiently recognized malignant HLA-A2(pos) B cells endogenously expressing CD20, including patient-derived follicular lymphoma and chronic lymphocytic leukemia (CLL) cells. In contrast, a wide range of HLA-A2(pos)CD20(neg) cells representing different tissue origins, and HLA-A2(neg)CD20(pos) cells, were not recognized. Cytotoxic T cells re-directed with CD20p/HLA-A2-specific TCRs or CD19 CARs responded with similar potencies to cells endogenously expressing comparable levels of CD20 and CD19. The CD20p/HLA-A2-specific TCRs recognized CD20p bound to HLA-A2 with high functional avidity. The results show that T cells expressing CD20p/HLA-A2-specific TCRs efficiently and specifically target B cells. When used in context of an HLA-haploidentical allogeneic stem cell transplantation where the donor is HLA-A2(neg) and the patient HLA-A2(pos), these T cells would selectively kill patient-derived B cells and allow reconstitution of the B-cell compartment with HLA-A2(neg) donor cells. These results should pave the way for clinical testing of T cells genetically engineered to target malignant B cells without permanent depletion of normal B cells. C1 [Mensali, Nadia; Ying, Fan; Sheng, Vincent Oei Yi; Yang, Weiwen; Walseng, Even; Kumari, Shraddha; Fallang, Lars-Egil; Malmberg, Karl Johan; Walchli, Sebastien; Olweus, Johanna] Oslo Univ Hosp, Radiumhosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway. [Mensali, Nadia; Ying, Fan; Sheng, Vincent Oei Yi; Yang, Weiwen; Kumari, Shraddha; Kolstad, Arne; Malmberg, Karl Johan; Olweus, Johanna] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Canc Immunotherapy, Oslo, Norway. [Kolstad, Arne] Oslo Univ Hosp, Radiumhosp, Dept Oncol, Oslo, Norway. [Uckert, Wolfgang] Humboldt Univ, Max Delbruck Ctr Mol Med, Berlin, Germany. [Uckert, Wolfgang] Humboldt Univ, Inst Biol, Berlin, Germany. [Malmberg, Karl Johan] Karolinska Inst, Ctr Infect Med, Dept Med, Stockholm, Sweden. [Walchli, Sebastien] Oslo Univ Hosp, Radiumhosp, Dept Cell Therapy, Oslo, Norway. [Walseng, Even] NIH, Bldg 10, Bethesda, MD 20892 USA. [Fallang, Lars-Egil] Biogen, Oslo, Norway. RP Olweus, J (reprint author), Oslo Univ Hosp, Radiumhosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.; Olweus, J (reprint author), Univ Oslo, Inst Clin Med, KG Jebsen Ctr Canc Immunotherapy, Oslo, Norway. EM Johanna.olweus@medisin.uio.no FU Research Council of Norway; K.G. Jebsen Foundation; Oslo University Hospital Radiumhospitalet Gene therapy program; University of Oslo; Regional Health Authorities South-Eastern Norway/Helse Sor-Ost FX This work was financed by the Research Council of Norway, the K.G. Jebsen Foundation, Oslo University Hospital Radiumhospitalet Gene therapy program, the University of Oslo and the Regional Health Authorities South-Eastern Norway/Helse Sor-Ost. NR 72 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 5 AR e1138199 DI 10.1080/2162402X.2016.1138199 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA DQ4GN UT WOS:000379162200049 PM 27467957 ER PT S AU Xu, M Motabar, O Ferrer, M Marugan, JJ Zheng, W Ottinger, EA AF Xu, Miao Motabar, Omid Ferrer, Marc Marugan, Juan J. Zheng, Wei Ottinger, Elizabeth A. GP New York Acad Sci TI Disease models for the development of therapies for lysosomal storage diseases SO TARGETING THE LYSOSOME SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE lysosomal storage diseases; therapeutic development; cell-based disease model; induced pluripotent stem cells; animal models ID ENZYME-REPLACEMENT THERAPY; PLURIPOTENT STEM-CELLS; NIEMANN-PICK-DISEASE; TYPE-1 GAUCHER-DISEASE; MUCOPOLYSACCHARIDOSIS TYPE-I; ANIMAL-MODELS; C DISEASE; POMPE DISEASE; NEURODEGENERATIVE DISEASES; PHARMACOLOGICAL CHAPERONE AB Lysosomal storage diseases (LSDs) are a group of rare diseases in which the function of the lysosome is disrupted by the accumulation of macromolecules. The complexity underlying the pathogenesis of LSDs and the small, often pediatric, population of patients make the development of therapies for these diseases challenging. Current treatments are only available for a small subset of LSDs and have not been effective at treating neurological symptoms. Disease-relevant cellular and animal models with high clinical predictability are critical for the discovery and development of new treatments for LSDs. In this paper, were view how LSD patient primary cells and induced pluripotent stem cell-derived cellular models are providing novel assay systems in which phenotypes are more similar to those of the human LSD physiology. Furthermore, larger animal disease models are providing additional tools for evaluation of the efficacy of drug candidates. Early predictors of efficacy and better understanding of disease biology can significantly affect the translational process by focusing efforts on those therapies with the higher probability of success, thus decreasing overall time and cost spent in clinical development and increasing the overall positive outcomes in clinical trials. C1 [Xu, Miao; Motabar, Omid; Ferrer, Marc; Marugan, Juan J.; Zheng, Wei; Ottinger, Elizabeth A.] NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20850 USA. [Xu, Miao] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Hangzhou, Zhejiang, Peoples R China. RP Ottinger, EA (reprint author), NIH, Div Preclin Innovat, NCATS, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20850 USA. EM elizabeth.ottinger@nih.gov RI Zheng, Wei/J-8889-2014 OI Zheng, Wei/0000-0003-1034-0757 FU Intramural NIH HHS [Z99 TR999999] NR 117 TC 1 Z9 1 U1 5 U2 6 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2016 VL 1371 BP 15 EP 29 DI 10.1111/nyas.13052 PG 15 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA BF0PB UT WOS:000379215100002 PM 27144735 ER PT J AU Baggott, MJ Garrison, KJ Coyle, JR Galloway, GP Barnes, AJ Huestis, MA Mendelson, JE AF Baggott, Matthew J. Garrison, Kathleen J. Coyle, Jeremy R. Galloway, Gantt P. Barnes, Allan J. Huestis, Marilyn A. Mendelson, John E. TI MDMA Impairs Response to Water Intake in Healthy Volunteers SO ADVANCES IN PHARMACOLOGICAL SCIENCES LA English DT Article ID ANTIDIURETIC-HORMONE SECRETION; ARGININE-VASOPRESSIN RELEASE; SPRAGUE-DAWLEY RATS; ECSTASY INGESTION; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; ACUTE HYPONATREMIA; SEX-DIFFERENCES; PLASMA COPEPTIN; CEREBRAL EDEMA; METABOLITES AB Hyponatremia is a serious complication of 3,4-methylenedioxymethamphetamine (MDMA) use. We investigated potential mechanisms in two double-blind, placebo-controlled studies. In Study 1, healthy drug-experienced volunteers received MDMA or placebo alone and in combination with the alpha-1 adrenergic inverse agonist prazosin, used as a positive control to release antidiuretic hormone (ADH). In Study 2, volunteers received MDMA or placebo followed by standardized water intake. MDMA lowered serum sodium but did not increase ADH or copeptin, although the control prazosin did increase ADH. Water loading reduced serum sodium more after MDMA than after placebo. There was a trend for women to have lower baseline serum sodium than men, but there were no significant interactions with drug condition. Combining studies, MDMA potentiated the ability of water to lower serum sodium. Thus, hyponatremia appears to be a significant risk when hypotonic fluids are consumed during MDMA use. Clinical trials and events where MDMA use is common should anticipate and mitigate this risk. C1 [Baggott, Matthew J.; Garrison, Kathleen J.; Galloway, Gantt P.; Mendelson, John E.] Friends Res Inst, Addict & Pharmacol Res Lab, Baltimore, MD 21201 USA. [Coyle, Jeremy R.] Univ Calif Berkeley, Sch Publ Hlth, Div Biostat, Berkeley, CA 94720 USA. [Barnes, Allan J.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, IRP, NIH, Baltimore, MD 21224 USA. RP Baggott, MJ (reprint author), Friends Res Inst, Addict & Pharmacol Res Lab, Baltimore, MD 21201 USA. EM matthew@baggott.net NR 66 TC 0 Z9 0 U1 2 U2 2 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 1687-6334 EI 1687-6342 J9 ADV PHARMACOL SCI JI Adv. Pharmacol. Sci. PY 2016 AR 2175896 DI 10.1155/2016/2175896 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DP7TG UT WOS:000378701500001 ER PT J AU Stelzer, G Plaschkes, I Oz-Levi, D Alkelai, A Olender, T Zimmerman, S Twik, M Belinky, F Fishilevich, S Nudel, R Guan-Golan, Y Warshawsky, D Dahary, D Kohn, A Mazor, Y Kaplan, S Stein, TI Baris, HN Rappaport, N Safran, M Lancet, D AF Stelzer, Gil Plaschkes, Inbar Oz-Levi, Danit Alkelai, Anna Olender, Tsviya Zimmerman, Shahar Twik, Michal Belinky, Frida Fishilevich, Simon Nudel, Ron Guan-Golan, Yaron Warshawsky, David Dahary, Dvir Kohn, Asher Mazor, Yaron Kaplan, Sergey Stein, Tsippi Iny Baris, Hagit N. Rappaport, Noa Safran, Marilyn Lancet, Doron TI VarElect: the phenotype-based variation prioritizer of the GeneCards Suite SO BMC GENOMICS LA English DT Article; Proceedings Paper CT 5th Variant-Interpretation-Special-Interest-Group Meeting (VarI-SIG) held at the Joint ISMB/ECCB Meeting CY JUL 11, 2015 CL Dublin, IRELAND SP Variant Interpretat Special Interest Grp, ISMB, ECCB DE Variant selection; Gene prioritization; Phenotyping; Phenotype interpretation; Next generation sequencing analysis; Guilt by association ID EXOME; DISEASES; GENES; IDENTIFICATION; DIAGNOSIS; VARIANTS; PROTEINS; GENOMICS; SERVER AB Background: Next generation sequencing (NGS) provides a key technology for deciphering the genetic underpinnings of human diseases. Typical NGS analyses of a patient depict tens of thousands non-reference coding variants, but only one or very few are expected to be significant for the relevant disorder. In a filtering stage, one employs family segregation, rarity in the population, predicted protein impact and evolutionary conservation as a means for shortening the variation list. However, narrowing down further towards culprit disease genes usually entails laborious seeking of gene-phenotype relationships, consulting numerous separate databases. Thus, a major challenge is to transition from the few hundred shortlisted genes to the most viable disease-causing candidates. Results: We describe a novel tool, VarElect (http://ve.genecards.org), a comprehensive phenotype-dependent variant/gene prioritizer, based on the widely-used GeneCards, which helps rapidly identify causal mutations with extensive evidence. The GeneCards suite offers an effective and speedy alternative, whereby > 120 gene-centric automatically-mined data sources are jointly available for the task. VarElect cashes on this wealth of information, as well as on GeneCards' powerful free-text Boolean search and scoring capabilities, proficiently matching variant-containing genes to submitted disease/symptom keywords. The tool also leverages the rich disease and pathway information of MalaCards, the human disease database, and PathCards, the unified pathway (SuperPaths) database, both within the GeneCards Suite. The VarElect algorithm infers direct as well as indirect links between genes and phenotypes, the latter benefitting from GeneCards' diverse gene-to-gene data links in GenesLikeMe. Finally, our tool offers an extensive gene-phenotype evidence portrayal ("MiniCards") and hyperlinks to the parent databases. Conclusions: We demonstrate that VarElect compares favorably with several often-used NGS phenotyping tools, thus providing a robust facility for ranking genes, pointing out their likelihood to be related to a patient's disease. VarElect's capacity to automatically process numerous NGS cases, either in stand-alone format or in VCF-analyzer mode (TGex and VarAnnot), is indispensable for emerging clinical projects that involve thousands of whole exome/genome NGS analyses. C1 [Stelzer, Gil; Oz-Levi, Danit; Alkelai, Anna; Olender, Tsviya; Zimmerman, Shahar; Twik, Michal; Fishilevich, Simon; Nudel, Ron; Stein, Tsippi Iny; Rappaport, Noa; Safran, Marilyn; Lancet, Doron] Weizmann Inst Sci, Dept Mol Genet, Rehovot, Israel. [Stelzer, Gil; Plaschkes, Inbar; Dahary, Dvir; Mazor, Yaron; Kaplan, Sergey] LifeMap Sci Ltd, Tel Aviv, Israel. [Belinky, Frida] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Guan-Golan, Yaron; Warshawsky, David; Kohn, Asher] LifeMap Sci Inc, Marshfield, MA 02050 USA. [Dahary, Dvir] Toldot Genet Ltd, Hod Hasharon, Israel. [Baris, Hagit N.] Rambam Hlth Care Campus, Genet Inst, Haifa, Israel. [Baris, Hagit N.] Technion Israel Inst Technol, Rappaport Sch Med, Haifa, Israel. RP Lancet, D (reprint author), Weizmann Inst Sci, Dept Mol Genet, Rehovot, Israel. EM doron.lancet@weizmann.ac.il FU NHGRI NIH HHS [U41 HG003345] NR 34 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2016 VL 17 SU 2 AR 444 DI 10.1186/s12864-016-2722-2 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA DQ0NK UT WOS:000378896000007 PM 27357693 ER PT J AU Weyemi, U Redon, CE Bonner, WM AF Weyemi, Urbain Redon, Christophe E. Bonner, William M. TI H2AX and EMT: deciphering beyond DNA repair SO CELL CYCLE LA English DT Editorial Material DE cancer; EMT; Histone H2A.X; metastasis; proliferation ID EPITHELIAL-MESENCHYMAL TRANSITION C1 [Weyemi, Urbain; Redon, Christophe E.; Bonner, William M.] NCI, Dev Therapeut Branch, Mol Pharmacol Lab, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. [Weyemi, Urbain] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, 725 N Wolfe St,WBSB 816, Baltimore, MD 21205 USA. RP Bonner, WM (reprint author), NCI, Dev Therapeut Branch, Mol Pharmacol Lab, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.; Weyemi, U (reprint author), Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, 725 N Wolfe St,WBSB 816, Baltimore, MD 21205 USA. EM sweyemi1@jhmi.edu; bonnerw@mail.nih.gov NR 7 TC 0 Z9 0 U1 2 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2016 VL 15 IS 10 BP 1305 EP 1306 DI 10.1080/15384101.2016.1160659 PG 2 WC Cell Biology SC Cell Biology GA DP8CS UT WOS:000378726100001 PM 26986807 ER PT J AU Marina, RJ Oberdoerffer, S AF Marina, Ryan J. Oberdoerffer, Shalini TI Epigenomics meets splicing through the TETs and CTCF SO CELL CYCLE LA English DT Editorial Material DE Alternative splicing; CTCF; TET1; TET2; 5hmC; 5caC ID OXIDATION C1 [Marina, Ryan J.] Univ Calif San Diego, San Diego, CA 92103 USA. [Oberdoerffer, Shalini] NCI, Ctr Canc Res, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP Oberdoerffer, S (reprint author), NCI, Lab Receptor Biol & Gene Express, Bldg 41,Room B626, Bethesda, MD 20892 USA. EM shalini.oberdoerffer@nih.gov NR 7 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 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PY 2016 VL 15 IS 11 BP 1397 EP 1399 DI 10.1080/15384101.2016.1171650 PG 3 WC Cell Biology SC Cell Biology GA DP8CX UT WOS:000378726600005 PM 27104639 ER PT J AU Earnshaw, WC Molina, O Ruppert, J Masomoto, H Kouprina, N Larionov, V AF Earnshaw, W. C. Molina, O. Ruppert, J. Masomoto, H. Kouprina, N. Larionov, V. TI 21st International Chromosome Conference (ICC). July 10-13, Foz do IguaCu, Brazil Abstracts SO CYTOGENETIC AND GENOME RESEARCH LA English DT Meeting Abstract CT 21st International Chromosome Conference (ICC) CY JUL 10-13, 2016 CL Foz do Iguacu, BRAZIL C1 [Earnshaw, W. C.; Molina, O.; Ruppert, J.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh, Midlothian, Scotland. [Masomoto, H.] Kazusa DNA Inst, Chiba, Japan. [Kouprina, N.; Larionov, V.] NCI, NIH, Bethesda, MD 20892 USA. EM bill.earnshaw@ed.ac.uk RI Molina, Oscar/P-4516-2016 OI Molina, Oscar/0000-0001-7585-4519 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 EI 1424-859X J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2016 VL 148 IS 2-3 BP 86 EP 86 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA DP8WA UT WOS:000378777400002 ER PT J AU Kouprina, N AF Kouprina, N. TI Human Artificial Chromosomes and TAR Cloning Technology for Genome Studies and Biomedicine SO CYTOGENETIC AND GENOME RESEARCH LA English DT Meeting Abstract CT 21st International Chromosome Conference (ICC) CY JUL 10-13, 2016 CL Foz do Iguacu, BRAZIL C1 [Kouprina, N.] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA. EM kouprinn@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 EI 1424-859X J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2016 VL 148 IS 2-3 MA VI.2 BP 141 EP 141 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA DP8WA UT WOS:000378777400139 ER PT J AU Marino, J Bergamo, NA Rocha, RH Curado, RMOF Hong, SK Hu, P Roessler, E Muenke, M Ribeiro-Bicudo, L AF Marino, J. Bergamo, N. A. Rocha, R. H. Curado, R. M. O. F. Hong, S. K. Hu, P. Roessler, E. Muenke, M. Ribeiro-Bicudo, L. TI Analysis of a Noncoding Region of the SIX3 Gene in Patients with Holoprosencephaly SO CYTOGENETIC AND GENOME RESEARCH LA English DT Meeting Abstract CT 21st International Chromosome Conference (ICC) CY JUL 10-13, 2016 CL Foz do Iguacu, BRAZIL C1 [Marino, J.] UNESP Sao Paulo State Univ Julio de Mesquita Filh, Sao Paulo, Brazil. [Marino, J.; Bergamo, N. A.; Rocha, R. H.; Curado, R. M. O. F.; Ribeiro-Bicudo, L.] Univ Fed Goias, Goiania, Go, Brazil. [Hong, S. K.; Hu, P.; Roessler, E.; Muenke, M.] NIH, Bldg 10, Bethesda, MD 20892 USA. EM jumarino22@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 EI 1424-859X J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2016 VL 148 IS 2-3 MA VII.12 BP 151 EP 151 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA DP8WA UT WOS:000378777400166 ER PT J AU Robbins, GK Cohn, SE Harrison, LJ Smeaton, L Moran, L Rusin, D Dehlinger, M Flynn, T Lammert, S Wu, AW Safren, SA Reynolds, NR AF Robbins, Gregory K. Cohn, Susan E. Harrison, Linda J. Smeaton, Laura Moran, Laura Rusin, David Dehlinger, Marjorie Flynn, Theresa Lammert, Sara Wu, Albert W. Safren, Steven A. Reynolds, Nancy R. TI Characteristics associated with virologic failure in high-risk HIV-positive participants with prior failure: a post hoc analysis of ACTG 5251 SO HIV CLINICAL TRIALS LA English DT Article DE Adherence; Antiretroviral therapy; High risk populations; Virologic failure ID ANTIRETROVIRAL THERAPY; UNITED-STATES; PERCEPTION QUESTIONNAIRE; CLINICAL-TRIALS; ADHERENCE; CARE; TRANSMISSION; PREVENTION; SUPPORT; ILLNESS AB Patients with prior virologic failure (VF) are at an increased risk of subsequent failure, emergence of resistance, and death. This analysis identifies outcomes and correlates of VF in a high-risk population. Methods: A5251 was designed to evaluate an enhanced adherence counseling intervention delivered by nurses from a central call site on virologic suppression. Due to slow enrollment, the study was closed prematurely and revised study endpoints were evaluated (week 24 VF (HIV-1 RNA >= 200 copies/ml) and non-perfect adherence (<100% self-reported using both the ACTG adherence questionnaire and visual analog scale (VAS)). Results: Fifty-nine participants were enrolled, 43 (73%) black non-Hispanic and 23 (39%) women. Median prior antiretroviral regimen changes were three and the co-morbidity in this population was higher than typical for HIV clinical trials. At week 24 (n = 41), 24 (59%) failed to reach virologic suppression (HIV-1 RNA <200 copies/ml) and 25 (63%) reported non-perfect adherence. Higher depression (CES-D10) and adverse illness perceptions (IPQ-B) were associated with week 24 non-adherence. Early clinical assessments (week 12 HIV-RNA = 200 copies/mL and non-perfect adherence) as well as higher depression and adverse illness perceptions were associated with week 24 VF. Discussion: In this high-risk population, the proportion of participants with suboptimal adherence and VF was unacceptably high. Interventions to address this treatment gap are clearly needed. Depression and a higher illness perception score, failure to achieve virologic suppression by week 12, and less than perfect adherence could be used to target individuals for early interventions in treatment-experienced, high-risk individuals at high risk for VF. C1 [Robbins, Gregory K.; Flynn, Theresa; Lammert, Sara] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Cohn, Susan E.] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. [Harrison, Linda J.; Smeaton, Laura] Harvard TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA USA. [Moran, Laura] Social & Sci Syst Inc, Silver Spring, MD USA. [Rusin, David] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. [Dehlinger, Marjorie] NIAID, NIH, Bethesda, MD 20892 USA. [Wu, Albert W.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Safren, Steven A.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Reynolds, Nancy R.] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. RP Robbins, GK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM grobbins@partners.org FU AIDS Clinical Trial Group; National Institute of Nursing Research FX AIDS Clinical Trial Group and National Institute of Nursing Research. NR 28 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1528-4336 EI 1945-5771 J9 HIV CLIN TRIALS JI HIV Clin. Trials PY 2016 VL 17 IS 4 BP 165 EP 172 DI 10.1080/15284336.2016.1189754 PG 8 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA DQ0PV UT WOS:000378903200005 PM 27347650 ER PT J AU Papanastasiou, L Fountoulakis, S Voulgaris, N Kounadi, T Choreftaki, T Kostopoulou, A Zografos, G Lyssikatos, C Stratakis, CA Piaditis, G AF Papanastasiou, Labrini Fountoulakis, Stelios Voulgaris, Nikos Kounadi, Theodora Choreftaki, Theodosia Kostopoulou, Akrivi Zografos, George Lyssikatos, Charalampos Stratakis, Constantine A. Piaditis, George TI Identification of a novel mutation of the PRKAR1A gene in a patient with Carney complex with significant osteoporosis and recurrent fractures SO HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM LA English DT Article DE Carney complex; Hypercortisolism; Osteoporosis; PRKAR1A gene; PPNAD ID NODULAR ADRENOCORTICAL DISEASE; REGULATORY SUBUNIT; CUSHINGS-SYNDROME; SPECTRUM; KINDREDS; MYXOMAS; LOCUS; 1A AB OBJECTIVE: Carney complex (CNC) is a rare autosomal dominant multiple neoplasia syndrome characterized by the presence of endocrine and non-endocrine tumors. More than 125 different germline mutations of the protein Kinase A type 1-alpha regulatory subunit (PRKAR1A) gene have been reported. We present a novel PRKAR1A gene germline mutation in a patient with severe osteoporosis and recurrent vertebral fractures. DESIGN: Clinical case report. CASE REPORT: A 53-year-old male with a medical history of surgically removed recurrent cardiac myxomas was evaluated for repeated low-pressure vertebral fractures and severe osteoporosis. Physical examination revealed spotty skin pigmentation of the lower extremities and papules in the nuchal and thoracic region. The presence of hypercortisolism due to micronodular adrenal disease and the history of cardiac myxomas suggested the diagnosis of CNC; the patient underwent detailed imaging investigation and genetic testing. METHODS: Standard imaging and clinical testing; DNA was sequenced by the Sanger method. RESULTS: Sequence analysis from peripheral lymphocytes DNA revealed a novel heterozygous point mutation at codon 172 of exon 2 (c.172G>T) of the PRKAR1A gene, resulting in early termination of the PRKAR1A transcript [p.Glu58Ter (E58X)]. CONCLUSION: We report a novel point mutation of the PRKAR1A gene in a patient with CNC who presented with significant osteoporosis and fractures. Low bone mineral density along with recurrent myxomas should point to the diagnosis of CNC. C1 [Papanastasiou, Labrini; Fountoulakis, Stelios; Voulgaris, Nikos; Kounadi, Theodora; Piaditis, George] G Gennimatas Gen Hosp, Dept Endocrinol, 154 Mesog Ave, Athens 11527, Greece. [Papanastasiou, Labrini; Fountoulakis, Stelios; Voulgaris, Nikos; Kounadi, Theodora; Piaditis, George] G Gennimatas Gen Hosp, Ctr Diabet, 154 Mesog Ave, Athens 11527, Greece. [Choreftaki, Theodosia; Kostopoulou, Akrivi] G Gennimatas Gen Hosp, Dept Pathol, Athens 11527, Greece. [Zografos, George] G Gennimatas Gen Hosp, Dept Surg, Athens 11527, Greece. [Lyssikatos, Charalampos; Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Papanastasiou, L (reprint author), G Gennimatas Gen Hosp, Dept Endocrinol, 154 Mesog Ave, Athens 11527, Greece.; Papanastasiou, L (reprint author), G Gennimatas Gen Hosp, Ctr Diabet, 154 Mesog Ave, Athens 11527, Greece. EM linapapan@yahoo.gr FU Intramural Research Program (IRP) of the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA FX This work was supported by the Intramural Research Program (IRP) of the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD 20892, USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU HELLENIC ENDOCRINE SOC PI ATHENS PA 14 ALEXANDRAS AVE, ATHENS, 106 82, GREECE SN 1109-3099 J9 HORM-INT J ENDOCRINO JI Horm.-Int. J. Endocrinol. Metab. PD JAN-MAR PY 2016 VL 15 IS 1 BP 129 EP 135 DI 10.14310/horm.2002.1627 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DP9NJ UT WOS:000378822600017 PM 27377598 ER PT J AU Bond, ND Guo, J Hall, KD McPherron, AC AF Bond, Nichole D. Guo, Juen Hall, Kevin D. McPherron, Alexandra C. TI Modeling Energy Dynamics in Mice with Skeletal Muscle Hypertrophy Fed High Calorie Diets SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE Computational modeling; energy balance; fat oxidation; food intake; high-fat diet; myostatin; obesity; skeletal muscle hypertrophy ID MYOSTATIN-DEFICIENT MICE; BODY-COMPOSITION; FAT MASS; INSULIN-RESISTANCE; MAJOR DETERMINANT; FOOD-INTAKE; EXPENDITURE; GROWTH; SENSITIVITY; INHIBITION AB Retrospective and prospective studies show that lean mass or strength is positively associated with metabolic health. Mice deficient in myostatin, a growth factor that negatively regulates skeletal muscle mass, have increased muscle and body weights and are resistant to diet-induced obesity. Their leanness is often attributed to higher energy expenditure in the face of normal food intake. However, even obese animals have an increase in energy expenditure compared to normal weight animals suggesting this is an incomplete explanation. We have previously developed a computational model to estimate energy output, fat oxidation and respiratory quotient from food intake and body composition measurements to more accurately account for changes in body composition in rodents over time. Here we use this approach to understand the dynamic changes in energy output, intake, fat oxidation and respiratory quotient in muscular mice carrying a dominant negative activin receptor IIB expressed specifically in muscle. We found that muscular mice had higher food intake and higher energy output when fed either chow or a high-fat diet for 15 weeks compared to WT mice. Transgenic mice also matched their rate of fat oxidation to the rate of fat consumed better than WT mice. Surprisingly, when given a choice between high-fat diet and Ensure (R) drink, transgenic mice consumed relatively more calories from Ensure (R) than from the high-fat diet despite similar caloric intake to WT mice. When switching back and forth between diets, transgenic mice adjusted their intake more rapidly than WT to restore normal caloric intake. Our results show that mice with myostatin inhibition in muscle are better at adjusting energy intake and output on diets of different macronutrient composition than WT mice to maintain energy balance and resist weight gain. C1 [Bond, Nichole D.; McPherron, Alexandra C.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Guo, Juen; Hall, Kevin D.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP McPherron, AC (reprint author), MyoTherapeutics, Silver Spring, MD USA. EM amcpherron@myotherapeutics.com FU Intramural Research Program of the NIH; NIDDK FX We thank Jennifer Portas for genotyping mice. This work is supported by the Intramural Research Program of the NIH, NIDDK.; Funding by the Intramural Research Program of the NIH, NIDDK. NR 50 TC 0 Z9 0 U1 0 U2 0 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2016 VL 12 IS 5 BP 617 EP 630 DI 10.7150/ijbs.13525 PG 14 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA DP8WV UT WOS:000378779500007 PM 27076790 ER PT J AU Beydoun, MA Canas, JA Dore, GA Beydoun, HA Rostant, OS Fanelli-Kuczmarski, MT Evans, MK Zonderman, AB AF Beydoun, May A. Canas, Jose-Atilio Dore, Gregory A. Beydoun, Hind A. Rostant, Ola S. Fanelli-Kuczmarski, Marie T. Evans, Michele K. Zonderman, Alan B. TI Serum Uric Acid and Its Association with Longitudinal Cognitive Change Among Urban Adults SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Aging; cognition; serum uric acid; sex differences ID ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; MULTIPLE-SCLEROSIS; RENAL-DISEASE; WOMEN; PEROXYNITRITE; DYSFUNCTION; DEMENTIA; HYPERTENSION; MORTALITY AB Uric acid, a waste metabolite among humans, was linked to various cognitive outcomes. We describe sex and age-group specific associations of baseline serum uric acid (SUA(base)) and significant change in SUA(Delta SUA: 1 versus 0 = decrease versus no change; 2 versus 0 = increase versus no change) with longitudinal annual rate of cognitive change among a large sample of urban adults. Data from the Healthy Aging in Neighborhoods of Diversity across the Life Span study, 2004-2009 (visit 1) and 2009-2013 (visit 2) were used. Of 3,720 adults selected at baseline (age range: 30-64 y), complete data were available for N=1,487-1,602 with a mean repeat of 1.5-1.7 visits/participant. Cognitive test domains spanned attention, processing speed, learning/memory, executive function, visuo-spatial/visuo-construction ability, language/verbal, and global cognitive function. SUA was measured at both visits. Multiple mixed-effects regression analyses were conducted. In the total population, a higher SUA(base) was associated with a faster annual rate of decline on a measure of visual memory/visuo-construction ability (the Benton Visual Retention Test) by gamma = 0.07 with a standard error of 0.02, p < 0.001. Among older men, a significant increase in SUA was associated with slower decline on a test of attention/processing speed, namely Trailmaking test, Part A, measured in seconds to completion (gamma = -6.91 +/- 1.73, p < 0.001). In sum, a higher SUA(base) was associated with faster cognitive decline over-time in a visual memory/visuo-construction ability test. Delta SUA had particular beneficial effects of an increasing Delta SUA on the domain of attention/processing speed among older men. More longitudinal studies are needed to examine cognitive domain-specific effects of over-time change in SUA within sex and age groups. C1 [Beydoun, May A.; Dore, Gregory A.; Rostant, Ola S.; Evans, Michele K.; Zonderman, Alan B.] NIA, Lab Epidemiol & Populat Sci, NIH, IRP, 251 Bayview Blvd,Suite 100,Room 04B118, Baltimore, MD 21224 USA. [Canas, Jose-Atilio] Nemours Childrens Clin Jacksonville, Pediat Endocrinol Diabet & Metab, Jacksonville, FL USA. [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA. [Fanelli-Kuczmarski, Marie T.] Univ Delaware, Dept Behav Hlth & Nutr, Newark, DE USA. RP Beydoun, MA (reprint author), NIA, NIH Biomed Res Ctr, IRP, 251 Bayview Blvd,Suite 100,Room 04B118, Baltimore, MD 21224 USA. EM baydounm@mail.nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 FU NIA/NIH/IRP FX This study was supported in part by the NIA/NIH/IRP. The authors would like to thank Megan Williams and Danielle Shaked, NIA/NIH/IRP for the internal review of the manuscript. NR 47 TC 0 Z9 0 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2016 VL 52 IS 4 BP 1415 EP 1430 DI 10.3233/JAD-160028 PG 16 WC Neurosciences SC Neurosciences & Neurology GA DP9BQ UT WOS:000378792100022 PM 27104899 ER PT J AU Xie, ZQ Lee, YH Boeke, M Jilaveanu, LB Liu, ZZ Bottaro, DP Kluger, HM Shuch, B AF Xie, Zuoquan Lee, Young H. Boeke, Marta Jilaveanu, Lucia B. Liu, Zongzhi Bottaro, Donald P. Kluger, Harriet M. Shuch, Brian TI MET Inhibition in Clear Cell Renal Cell Carcinoma SO JOURNAL OF CANCER LA English DT Article DE HGF; MET; clear cell Carcinoma; VEGFR2; XL184; cabozantinib ID ENDOTHELIAL-CELLS; TYROSINE KINASE; TUMOR-CELLS; C-MET; GROWTH; PROTOONCOGENE; METASTASIS; HEPATOCYTE; MUTATIONS; PATHWAY AB Background: Clear cell renal cell carcinoma (ccRCC) is the most lethal form of kidney cancer. Small molecule VEGFR inhibitors are widely used but are not curative and various resistance mechanisms such as activation of the MET pathway have been described. Dual MET/VEGFR2 inhibitors have recently shown clinical benefit but limited preclinical data evaluates their effects in ccRCC. Methods: An interrogation of the Cancer Genome Atlas (TCGA) dataset was performed to evaluate oncogenic alterations in the MET/VEGFR2 pathway. We evaluated the in vitro effects of Cabozantinib, a dual MET/VEGFR2 inhibitor, using a panel of ccRCC cell lines. Drug effects of cell viability and proliferation, migration, cell scatter, anchorage independent growth, and downstream MET/VEGFR2 signaling pathways were assessed. Results: Twelve percent of TCGA cases had possible MET/HGF oncogenic alterations with co-occurrence noted (p<0.001). MET/HGF altered cases had worse overall survival (p=0.044). Cabozantinib was a potent inhibitor of MET and VEGFR2 in vitro in our cell line panel. PI3K, MAPK and mTOR pathways were also suppressed by cabozantinib, however the effects on cell viability in vitro were modest. At nanomolar concentrations of cabozantinib, HGF-stimulated migration, invasion, cellular scattering and soft agar colony formation were inhibited. Conclusions: We provide further preclinical rationale for dual MET/VEGFR2 inhibition in ccRCC. While the MET pathway is implicated in VEGFR resistance, dual inhibitors may have direct anti-tumor effects in a patient subset with evidence of MET pathway involvement. Cabozantinib is a potent dual MET/VEGFR2 inhibitor, significantly inhibits cell migration and invasion in vitro and likely has anti-angiogenic effects similar to other VEGFR tyrosine kinase inhibitors. Future work involving in vivo models will be useful to better define mechanisms of potential anti-tumor activity. C1 [Xie, Zuoquan; Boeke, Marta; Shuch, Brian] Yale Sch Med, Dept Urol, POB 208058, New Haven, CT 06520 USA. [Lee, Young H.; Bottaro, Donald P.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Jilaveanu, Lucia B.; Kluger, Harriet M.] Yale Sch Med, Dept Med, Sect Med Oncol, New Haven, CT 06520 USA. [Liu, Zongzhi] Yale Sch Med, Dept Pathol, New Haven, CT 06520 USA. [Xie, Zuoquan] Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China. RP Shuch, B (reprint author), Yale Sch Med, Dept Urol, POB 208058, New Haven, CT 06520 USA. EM Brian.shuch@yale.edu FU CTSA Grant from the National Center for Advancing Translational Science (NCATS), a component of the National Institutes of Health (NIH) [KL2 TR000140]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; China Scholarship Council [201404910330] FX This publication was made possible by CTSA Grant Number KL2 TR000140 from the National Center for Advancing Translational Science (NCATS), a component of the National Institutes of Health (NIH). This work was also supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH. We acknowledge the funding of China Scholarship Council for Zuoquan Xie (NO.201404910330). NR 29 TC 2 Z9 2 U1 2 U2 4 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2016 VL 7 IS 10 BP 1205 EP 1214 DI 10.7150/jca.14604 PG 10 WC Oncology SC Oncology GA DQ0UH UT WOS:000378916200004 PM 27390595 ER PT J AU He, MX Chen, KT Li, SH Zhang, SM Zheng, JM Hu, XX Gao, L Chen, J Song, XM Zhang, WP Wang, JM Yang, JM AF He, Miaoxia Chen, Keting Li, Suhong Zhang, Shimin Zheng, Jianming Hu, Xiaoxia Gao, Lei Chen, Jie Song, Xianmin Zhang, Weiping Wang, Jianmin Yang, Jianmin TI Clinical Significance of "Double-hit" and "Double-protein" expression in Primary Gastric B-cell Lymphomas SO JOURNAL OF CANCER LA English DT Article DE Primary gastric B-cell lymphoma; Double-hit; Double-protein; MVD; SPARC; Fluorescent in situ hybridization; Immunohistochemistry and Tumor tissue microarray ID MARGINAL ZONE LYMPHOMA; MICROVESSEL DENSITY; MALT LYMPHOMA; RITUXIMAB; SURVIVAL; MANAGEMENT; SIGNATURES; PREDICTS; SURGERY; TISSUE AB BACKGROUND AND AIMS: Primary gastric B-cell lymphoma is the second most common malignancy of the stomach. There are many controversial issues about its diagnosis, treatment and clinical management. "Double-hit" and "double-protein" involving gene rearrangement and protein expression of c-Myc and bcl2/bcl6 are the most used terms to describe DLBCL poor prognostic factors in recent years. However, very little is known about the role of these prognostic factors in primary gastric B-cell lymphomas. This study aims to obtain a molecular pathology prognostic model of gastric B-cell lymphoma for clinical stratified management by evaluating how the "double-hit" and "double-protein" in tumor cells as well as microenvironmental reaction of tumor stromal tissue affect clinical outcome in primary gastric B-cell lymphomas. METHODS: Data and tissues of 188 cases diagnosed with gastric B-cell lymphomas were used in this study. Tumor tissue microarray (TMA) of formalin fixed and paraffin embedded (FFPE) tissues was constructed for fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) analysis with a serial of biomarkers containing MYC, BCL2, BCL6, CD31, SPARC, CD10, MUM1 and Ki-67. Modeled period analysis was used to estimate 3-year and 5-year overall survival (OS) and disease-free survival (DFS) distributions. RESULTS: There was no definite "double-hit" case though the gene rearrangement of c-Myc (5.9%), bcl2 (0.1%) and bcl6 (7.4%) was found in gastric B-cell lymphomas. The gene amplification or copy gains of c-Myc (10.1%), bcl-2 (17.0%) and bcl-6 (0.9%) were present in these lymphomas. There were 12 cases of the lymphomas with the "double-protein" expression of MYC and BCL2/BCL6. All patients with "double-protein" gastric B-cell lymphomas had poor outcome compared with those without. More importantly, "MYC-BCL2-BCL6" negative group of gastric B-cell lymphoma patients had favorable clinical outcome regardless clinical stage, pathological types and therapeutic modalities. And the similar better prognosis was found in the cases with low microvessel density (MVD) in tumor tissue and high expression of SPARC (SPARC >= 5%) in stromal cells. CONCLUSIONS: "Double-hit" lymphoma was rare among primary gastric lymphoma, while patients with multiple gene amplification and/or copy gains of c-Myc, bcl2 and bcl6, and "double-protein" gastric B-cell lymphomas had a poor clinical outcome. In addition, patients with MYC, BCL2 and BCL6 expression negative or low MVD in tumor tissue with high expression of SPARC in stromal cells could have better prognosis than other gastric B-cell lymphomas regardless of their clinical stage and pathological types. These results would be of very importance for clinical stratified management and precision medicine of gastric B-cell lymphomas. C1 [He, Miaoxia; Zheng, Jianming] Second Mil Med Univ, Dept Pathol, Changhai Hosp, Shanghai 200433, Peoples R China. [He, Miaoxia] NIH, Mol Pathol, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. [Chen, Keting; Hu, Xiaoxia; Gao, Lei; Chen, Jie; Song, Xianmin; Zhang, Weiping; Wang, Jianmin; Yang, Jianmin] Second Mil Med Univ, Dept Hematol, Changhai Hosp, Shanghai 200433, Peoples R China. [Li, Suhong] Children Hosp, Dept Pathol, Taiyuan 030013, Peoples R China. [Li, Suhong] Women Hlth Ctr Shanxi, Taiyuan 030013, Peoples R China. [Zhang, Shimin] Joint Pathol Ctr, Div Mol Pathol, Washington, DC 20817 USA. RP Zheng, JM (reprint author), Second Mil Med Univ, Dept Pathol, Changhai Hosp, Shanghai 200433, Peoples R China.; Yang, JM (reprint author), Second Mil Med Univ, Dept Hematol, Changhai Hosp, Shanghai 200433, Peoples R China. EM jmzheng1962@163.com; yangjianmin@csco.org.cn FU National Natural Science Foundation of China [81372544] FX This study was supported by the National Natural Science Foundation of China (Project No. 81372544). NR 32 TC 0 Z9 0 U1 4 U2 4 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2016 VL 7 IS 10 BP 1215 EP 1225 DI 10.7150/jca.15395 PG 11 WC Oncology SC Oncology GA DQ0UH UT WOS:000378916200005 PM 27390596 ER PT J AU Meijer, L Nelson, DJ Riazanski, V Gabdoulkhakova, AG Hery-Arnaud, G Le Berre, R Loaec, N Oumata, N Galons, H Nowak, E Gueganton, L Dorothee, G Prochazkova, M Hall, B Kulkarni, AB Gray, RD Rossi, AG Witko-Sarsat, V Norez, C Becq, F Ravel, D Mottier, D Rault, G AF Meijer, Laurent Nelson, Deborah J. Riazanski, Vladimir Gabdoulkhakova, Aida G. Hery-Arnaud, Genevieve Le Berre, Rozenn Loaec, Nadege Oumata, Nassima Galons, Herve Nowak, Emmanuel Gueganton, Laetitia Dorothee, Guillaume Prochazkova, Michaela Hall, Bradford Kulkarni, Ashok B. Gray, Robert D. Rossi, Adriano G. Witko-Sarsat, Veronique Norez, Caroline Becq, Frederic Ravel, Denis Mottier, Dominique Rault, Gilles TI Modulating Innate and Adaptive Immunity by (R)-Roscovitine: Potential Therapeutic Opportunity in Cystic Fibrosis SO JOURNAL OF INNATE IMMUNITY LA English DT Review DE CFTR; Corrector; Cystic fibrosis; Infection; Inflammation; Innate immunity; Pseudomonas aeruginosa; Roscovitine; Seliciclib; TRPC6 ID DEPENDENT KINASE INHIBITOR; TRANSMEMBRANE CONDUCTANCE REGULATOR; NEUTROPHIL EXTRACELLULAR TRAPS; ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; PSEUDOMONAS-AERUGINOSA INFECTION; T-CELL DIFFERENTIATION; D-ASPARTATE RECEPTOR; R-ROSCOVITINE; LUNG-DISEASE; TRP CHANNELS AB (R)-Roscovitine, a pharmacological inhibitor of kinases, is currently in phase II clinical trial as a drug candidate for the treatment of cancers, Cushing's disease and rheumatoid arthritis. We here review the data that support the investigation of (R)-roscovitine as a potential therapeutic agent for the treatment of cystic fibrosis (CF). (R)-Roscovitine displays four independent properties that may favorably combine against CF: (1) it partially protects F508del-CFTR from proteolytic degradation and favors its trafficking to the plasma membrane; (2) by increasing membrane targeting of the TRPC6 ion channel, it rescues acidification in phagolysosomes of CF alveolar macrophages (which show abnormally high pH) and consequently restores their bactericidal activity; (3) its effects on neutrophils (induction of apoptosis), eosinophils (inhibition of degranulation/induction of apoptosis) and lymphocytes (modification of the Th17/Treg balance in favor of the differentiation of anti-inflammatory lymphocytes and reduced production of various interleukins, notably IL-17A) contribute to the resolution of inflammation and restoration of innate immunity, and (4) roscovitine displays analgesic properties in animal pain models. The fact that (R)-roscovitine has undergone extensive preclinical safety/pharmacology studies, and phase I and II clinical trials in cancer patients, encourages its repurposing as a CF drug candidate. (C) 2016 S. Karger AG, Basel C1 [Meijer, Laurent; Loaec, Nadege; Oumata, Nassima] ManRos Therapeut, Ctr Perharidy, FR-29680 Roscoff, France. [Nelson, Deborah J.; Riazanski, Vladimir; Gabdoulkhakova, Aida G.] Univ Chicago, Dept Pharmacol & Physiol Sci, 947 E 58th St, Chicago, IL 60637 USA. [Hery-Arnaud, Genevieve] CHRU Brest, Hop Cavale Blanche, Unite Bacteriol, Brest, France. [Hery-Arnaud, Genevieve; Le Berre, Rozenn] Univ Brest, UFR Med & Sci Sante, LUBEM EA3882, Brest, France. [Le Berre, Rozenn] CHRU Brest, Dept Med Interne & Pneumol, Brest, France. [Galons, Herve] Univ Paris 05, Unite Technol Chim & Biol Sante, INSERM, UMR S 1022, Paris, France. [Nowak, Emmanuel; Mottier, Dominique] CHRU Brest, Hop Cavale Blanche, Ctr Invest Clin, INSERM,CIC 1412, Brest, France. [Gueganton, Laetitia; Rault, Gilles] Fdn Ildys, Roscoff, France. [Dorothee, Guillaume] INSERM, UMRS 938,CdR St Antoine, Immune Syst Neuroinflammat & Neurodegenerat Dis L, Inflammat Immunopathol Biotherapy Dept DHU i2B, Paris, France. [Dorothee, Guillaume] Sorbonne Univ, Univ Paris 06, Hop St Antoine, CdR St Antoine,UMRS 938, Paris, France. [Prochazkova, Michaela; Hall, Bradford; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. [Gray, Robert D.; Rossi, Adriano G.] Univ Edinburgh, Sch Med, Queens Med Res Inst, MRC Ctr Inflammat Res, Edinburgh, Midlothian, Scotland. [Witko-Sarsat, Veronique] Univ Paris 05, CNRS, UMR 8104, Inst Cochin,INSERM,U1016, Paris, France. [Norez, Caroline; Becq, Frederic] Univ Poitiers, CNRS, Lab Signalisat & Transports Ion Membranaires, Poitiers, France. [Ravel, Denis] Initial R&D Consulting, Paris, France. RP Meijer, L (reprint author), ManRos Therapeut, Ctr Perharidy, FR-29680 Roscoff, France. EM meijer@manros-therapeutics.com RI DOROTHEE, Guillaume/O-9760-2016; Becq, Frederic/P-9233-2016; Norez, Caroline/P-9567-2016; OI Becq, Frederic/0000-0003-3915-0973; Gabdoulkhakova, Aida/0000-0002-8437-4389 FU associations Vaincre la Mucoviscidose; ABCF Mucoviscidose; LabEx INFLAMEX [ANR-11-IDEX-0005-02]; Chancellerie des Universites de Paris (Legs Poix); National Institutes of Health Grants (USA) [RO1 GM36823, RO1 HL125076]; Cystic Fibrosis Foundation [12 PO, 13PO] FX This work was supported by the associations Vaincre la Mucoviscidose, ABCF Mucoviscidose, the LabEx INFLAMEX (ANR-11-IDEX-0005-02), and the Chancellerie des Universites de Paris (Legs Poix; V.W.-S.) and National Institutes of Health Grants (USA) RO1 GM36823 and RO1 HL125076, and Cystic Fibrosis Foundation Grants 12 PO and 13PO (D.J.N.). NR 246 TC 4 Z9 4 U1 8 U2 10 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X EI 1662-8128 J9 J INNATE IMMUN JI J. Innate Immun. PY 2016 VL 8 IS 4 BP 330 EP 349 DI 10.1159/000444256 PG 20 WC Immunology SC Immunology GA DP9DQ UT WOS:000378797300002 PM 26987072 ER PT J AU Carevic, M Oz, H Fuchs, K Laval, J Schroth, C Frey, N Hector, A Bilich, T Haug, M Schmidt, A Autenrieth, SE Bucher, K Beer-Hammer, S Gaggar, A Kneilling, M Benarafa, C Gao, JL Murphy, PM Schwarz, S Moepps, B Hartl, D AF Carevic, M. Oez, H. Fuchs, K. Laval, J. Schroth, C. Frey, N. Hector, A. Bilich, T. Haug, M. Schmidt, A. Autenrieth, S. E. Bucher, K. Beer-Hammer, S. Gaggar, A. Kneilling, M. Benarafa, C. Gao, J. L. Murphy, P. M. Schwarz, S. Moepps, B. Hartl, D. TI CXCR1 Regulates Pulmonary Anti-Pseudomonas Host Defense SO JOURNAL OF INNATE IMMUNITY LA English DT Article DE CXCR1; Chemokine receptors; Pseudomonas; Neutrophils; Cystic fibrosis; Toll-like receptor 5; Reactive oxygen species ID FIBROSIS LUNG-DISEASE; PSEUDOMONAS-AERUGINOSA INFECTION; CYSTIC-FIBROSIS; CHEMOKINE RECEPTORS; NEUTROPHILS; TLR5; PATHOGENESIS; GCP-2/CXCL6; ACTIVATION; EXPRESSION AB Pseudomonas aeruginosa is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-P. aeruginosa immunity remain incompletely understood. Here we demonstrate, by studying an airway P. aeruginosa infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against P. aeruginosa. Mechanistically, CXCR1 regulates anti-Pseudomonas neutrophil responses through modulation of reactive oxygen species and interference with Toll-like receptor 5 expression. These studies define CXCR1 as a novel, noncanonical chemokine receptor that regulates pulmonary anti-Pseudomonas host defense with broad implications for CF, COPD and other infectious lung diseases. (C) 2016 S. Karger AG, Basel C1 [Carevic, M.; Oez, H.; Laval, J.; Schroth, C.; Frey, N.; Hector, A.; Bilich, T.; Hartl, D.] Univ Tubingen, Childrens Hosp, Hoppe Seyler Str 1, DE-72076 Tubingen, Germany. [Carevic, M.; Oez, H.; Laval, J.; Schroth, C.; Frey, N.; Hector, A.; Bilich, T.; Hartl, D.] Univ Tubingen, Interdisciplinary Ctr Infect Dis, Hoppe Seyler Str 1, DE-72076 Tubingen, Germany. [Haug, M.; Schmidt, A.; Schwarz, S.] Univ Tubingen, Dept Med Microbiol, DE-72076 Tubingen, Germany. [Autenrieth, S. E.] Univ Tubingen, Dept Internal Med 2, DE-72076 Tubingen, Germany. [Bucher, K.; Beer-Hammer, S.] Univ Tubingen, Dept Pharmacol & Expt Therapy, DE-72076 Tubingen, Germany. [Fuchs, K.; Bucher, K.; Beer-Hammer, S.] Univ Tubingen, Interfac Ctr Pharmacogen & Drug Res, DE-72076 Tubingen, Germany. [Kneilling, M.] Univ Tubingen, Dept Preclin Imaging & Radiopharm, Werner Siemens Imaging Ctr, DE-72076 Tubingen, Germany. [Moepps, B.] Univ Ulm, Med Ctr, Inst Pharmacol & Toxicol, D-89069 Ulm, Germany. [Gaggar, A.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Gaggar, A.] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. [Gao, J. L.; Murphy, P. M.] NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Benarafa, C.] Univ Bern, Theodor Kocher Inst, Bern, Switzerland. RP Hartl, D (reprint author), Univ Tubingen, Childrens Hosp, Hoppe Seyler Str 1, DE-72076 Tubingen, Germany.; Hartl, D (reprint author), Univ Tubingen, Interdisciplinary Ctr Infect Dis, Hoppe Seyler Str 1, DE-72076 Tubingen, Germany. EM dominik.hartl@med.uni-tuebingen.de FU German Research Foundation (DFG, Emmy Noether Programme) [HA 5274/3-1]; Fritz-Thyssen-Foundation; CRC685 at Tubingen; Novartis Foundation; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA FX We thank Antje Munder and Burkhard Tummler, MHH Hannover Germany, for luciferase-expressing P. aeruginosa bacteria. This work was supported by the German Research Foundation (DFG, Emmy Noether Programme HA 5274/3-1 to D.H.), the Fritz-Thyssen-Foundation (A.H. and D.H.), the CRC685 at Tubingen and the Novartis Foundation (D.H.). This work was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA (P.M.M. and J.L.G.). NR 46 TC 2 Z9 2 U1 5 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X EI 1662-8128 J9 J INNATE IMMUN JI J. Innate Immun. PY 2016 VL 8 IS 4 BP 362 EP 373 DI 10.1159/000444125 PG 12 WC Immunology SC Immunology GA DP9DQ UT WOS:000378797300004 PM 26950764 ER PT J AU Federer, LM Lu, YL Joubert, DJ AF Federer, Lisa M. Lu, Ya-Ling Joubert, Douglas J. TI Data literacy training needs of biomedical researchers SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article DE Data Curation; Education, Continuing; Library Services; Libraries, Medical; Biomedical Research; Data Collection; Information Storage and Retrieval; Information Dissemination AB Objective: The research investigated topic priorities for data literacy training for biomedical researchers and staff. Methods: An electronic survey was used to assess researchers' level of knowledge related to data literacy skills and the relevance of these skills to their work. Results: Most respondents did not have any formal training in data literacy. Respondents considered most tasks highly relevant to their work but rated their expertise in tasks lower. Conclusion: Among this group, researchers have diverse data literacy training needs. Librarians' expertise makes them well suited to provide such training. C1 [Federer, Lisa M.; Lu, Ya-Ling; Joubert, Douglas J.] NIH, NIH Lib, Div Lib Serv, Off Res Serv, 10 Ctr Dr, Bethesda, MD USA. RP Federer, LM (reprint author), NIH, NIH Lib, Div Lib Serv, Off Res Serv, 10 Ctr Dr, Bethesda, MD USA. EM lisa.federer@nih.gov; ya-ling.lu@nih.gov; joubertd@ors.od.nih.gov OI Joubert, Douglas/0000-0003-4090-5587 NR 18 TC 0 Z9 0 U1 11 U2 16 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JAN PY 2016 VL 104 IS 1 BP 52 EP 57 DI 10.3163/1536-5050.104.1.008 PG 6 WC Information Science & Library Science SC Information Science & Library Science GA DP1OQ UT WOS:000378259700009 PM 26807053 ER PT J AU Gillikin, D AF Gillikin, David TI National Library of Medicine response SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Letter C1 [Gillikin, David] Natl Lib Med, Bibliog Serv Div, Bethesda, MD 20894 USA. RP Gillikin, D (reprint author), Natl Lib Med, Bibliog Serv Div, Bethesda, MD 20894 USA. EM gillikd@mail.nlm.nih.gov NR 2 TC 1 Z9 1 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JAN PY 2016 VL 104 IS 1 BP 84 EP 84 DI 10.3163/1536-5050.104.1.016 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA DP1OQ UT WOS:000378259700017 PM 26807061 ER PT S AU Faruque, J Antani, S Long, R Kim, L Thoma, G AF Faruque, Jessica Antani, Sameer Long, Rodney Kim, Lauren Thoma, George BE Abbey, CK Kupinski, MA TI Image Similarity Ranking of Focal Computed Tomography Liver Lesions Using a 2AFC Technique SO MEDICAL IMAGING 2016: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Perception, Observer Performance, and Technology Assessment CY MAR 02-03, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD DE Computed Tomography; image similarity; content-based image retrieval; liver; precision medicine ID CLUSTERED MICROCALCIFICATIONS; MAMMOGRAMS; RETRIEVAL; PERCEPTION; DIAGNOSIS; FUTURE; PAIRS AB Content-based image retrieval (CBIR) for radiological images has experienced massive growth over the past two decades, and shows great potential as a tool for use in precision medicine. A recurring challenge in CBIR evaluation has been in obtaining reference sets of images from human viewers of the system. Our work seeks to determine the feasibility of creating a reference set from images ranked by similarity from human viewers of the images. We obtained 2 sets each of 10 images of CT focal liver lesions from a database of open-access publications with and without markings showing the region containing the lesions, respectively. We created 2 sets of all 45 pair-wise combinations of the images, and displayed them to 10 volunteers, of which 2 had medical training. We used a Two-Alternative Forced Choice (2AFC) paradigm to obtain complete rankings of similarity levels in these image pairs. Analysis showed that inter-reader agreement for rankings ranged from Tau=0.21-0.69 (median=0.37) for the image pairs without any markings, and Tau=0.21-0.57 (median=0.33) for the image pairs with markings. A comparison of the regions of interests drawn by the study participants outlining the lesions in images without markings showed that participants tended to agree on images containing a single focal lesion of a single density, and inter-reader agreement for image rankings in which the regions of interest agree ranged from Tau=0.39-0.85 (median=0.58). These results show that the use of image ranking using 2AFC may be a feasible method for creating reference sets for CBIR system validation. C1 [Faruque, Jessica; Antani, Sameer; Long, Rodney; Thoma, George] NIH, Commun Engn Branch, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. [Kim, Lauren] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. RP Faruque, J (reprint author), NIH, Commun Engn Branch, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 23 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0022-5 J9 PROC SPIE PY 2016 VL 9787 AR 97870N DI 10.1117/12.2217364 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BF0CK UT WOS:000378534200022 ER PT S AU Castro, MA Pham, DL Butman, J AF Castro, Marcelo A. Pham, Dzung L. Butman, John BE Zhang, J Cook, TS TI Improved superficial brain hemorrhage visualization in susceptibility weighted images by constrained minimum intensity projection SO MEDICAL IMAGING 2016: PACS AND IMAGING INFORMATICS: NEXT GENERATION AND INNOVATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - PACS and Imaging Informatics - Next Generation and Innovations CY FEB 28-29, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD DE Susceptibility weighted imaging; Magnetic resonance imaging; Minimum intensity projection; Traumatic brain injury; Image segmentation ID MICROBLEEDS; MRI AB Minimum intensity projection is a technique commonly used to display magnetic resonance susceptibility weighted images, allowing the observer to better visualize hemorrhages and vasculature. The technique displays the minimum intensity in a given projection within a thick slab, allowing different connectivity patterns to be easily revealed. Unfortunately, the low signal intensity of the skull within the thick slab can mask superficial tissues near the skull base and other regions. Because superficial microhemorrhages are a common feature of traumatic brain injury, this effect limits the ability to proper diagnose and follow up patients. In order to overcome this limitation, we developed a method to allow minimum intensity projection to properly display superficial tissues adjacent to the skull. Our approach is based on two brain masks, the largest of which includes extracerebral voxels. The analysis of the rind within both masks containing the actual brain boundary allows reclassification of those voxels initially missed in the smaller mask. Morphological operations are applied to guarantee accuracy and topological correctness, and the mean intensity within the mask is assigned to all outer voxels. This prevents bone from dominating superficial regions in the projection, enabling superior visualization of cortical hemorrhages and vessels. C1 [Castro, Marcelo A.; Pham, Dzung L.] Henry M Jackson Fdn, Ctr Neurosci & Regenerat Med, 9000 Rockville Pike, Bethesda, MD USA. [Butman, John] NIH, Dept Radiol & Imaging Sci, Ctr Clin, 9000 Rockville Pike, Bethesda, MD USA. RP Castro, MA (reprint author), Henry M Jackson Fdn, Ctr Neurosci & Regenerat Med, 9000 Rockville Pike, Bethesda, MD USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0024-9 J9 PROC SPIE PY 2016 VL 9789 AR 97890D DI 10.1117/12.2216959 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BF0CU UT WOS:000378538300010 ER PT S AU Xue, ZY Antani, S Long, LR Demner-Fushman, D Thoma, GR AF Xue, Zhiyun Antani, Sameer Long, L. Rodney Demner-Fushman, Dina Thoma, George R. BE Zhang, J Cook, TS TI Improving Face Image Extraction by Using Deep Learning Technique SO MEDICAL IMAGING 2016: PACS AND IMAGING INFORMATICS: NEXT GENERATION AND INNOVATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - PACS and Imaging Informatics - Next Generation and Innovations CY FEB 28-29, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD DE image modality classification; deep learning; convolutional neural networks; face detection; Viola-Jones algorithm ID FEATURES AB The National Library of Medicine (NLM) has made a collection of over a 1.2 million research articles containing 3.2 million figure images searchable using the Open-i(SM) multimodal (text+image) search engine. Many images are visible light photographs, some of which are images containing faces ("face images"). Some of these face images are acquired in unconstrained settings, while others are studio photos. To extract the face regions in the images, we first applied one of the most widely-used face detectors, a pre-trained Viola-Jones detector implemented in Matlab and OpenCV. The Viola-Jones detector was trained for unconstrained face image detection, but the results for the NLM database included many false positives, which resulted in a very low precision. To improve this performance, we applied a deep learning technique, which reduced the number of false positives and as a result, the detection precision was improved significantly. (For example, the classification accuracy for identifying whether the face regions output by this Viola-Jones detector are true positives or not in a test set is about 96%.) By combining these two techniques (Viola-Jones and deep learning) we were able to increase the system precision considerably, while avoiding the need to manually construct a large training set by manual delineation of the face regions. C1 [Xue, Zhiyun; Antani, Sameer; Long, L. Rodney; Demner-Fushman, Dina; Thoma, George R.] NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. RP Xue, ZY (reprint author), NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 24 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0024-9 J9 PROC SPIE PY 2016 VL 9789 AR 97890J DI 10.1117/12.2216278 PG 11 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BF0CU UT WOS:000378538300016 ER PT S AU Sak, M Duric, N Littrup, P Sherman, ME Gierach, GL AF Sak, Mark Duric, Neb Littrup, Peter Sherman, Mark E. Gierach, Gretchen L. BE Duric, N Heyde, B TI Using ultrasound tomography to identify the distributions of density throughout the breast SO MEDICAL IMAGING 2016: ULTRASONIC IMAGING AND TOMOGRAPHY SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Ultrasonic Imaging and Tomography CY FEB 28-29, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD DE Ultrasound tomography; Breast density; Density distribution; Sound speed ID MAMMOGRAPHIC DENSITY; CANCER RISK; TISSUE AB Women with high breast density are at increased risk of developing breast cancer. Breast density has usually been defined using mammography as the ratio of fibroglandular tissue to total breast area. Ultrasound tomography (UST) is an emerging modality that can also be used to measure breast density. UST creates tomographic sound speed images of the patient's breast which is useful as sound speed is directly proportional to tissue density. Furthermore, the volumetric and quantitative information contained in the sound speed images can be used to describe the distribution of breast density. The work presented here measures the UST sound speed density distributions of 165 women with negative screening mammography. Frequency distributions of the sound speed voxel information were examined for each patient. In a preliminary analysis, the UST sound speed distributions were averaged across patients and grouped by various patient and density-related factors (e.g., age, body mass index, menopausal status, average mammographic breast density). It was found that differences in the distribution of density could be easily visualized for different patient groupings. Furthermore, findings suggest that the shape of the distributions may be used to identify participants with varying amounts of dense and non-dense tissue. C1 [Sak, Mark; Duric, Neb; Littrup, Peter] Delphinus Med Technol, 46701 Commerce Ctr Dr, Plymouth, MI 48170 USA. [Littrup, Peter] Brown Univ, Rhode Isl Hosp, 593 Eddy St, Providence, RI 02903 USA. [Sherman, Mark E.] NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Gierach, Gretchen L.] NCI, Metabol Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Sak, M (reprint author), Delphinus Med Technol, 46701 Commerce Ctr Dr, Plymouth, MI 48170 USA. RI Gierach, Gretchen/E-1817-2016 OI Gierach, Gretchen/0000-0002-0165-5522 NR 19 TC 0 Z9 0 U1 1 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0025-6 J9 PROC SPIE PY 2016 VL 9790 AR 979019 DI 10.1117/12.2217611 PG 11 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BF0CZ UT WOS:000378539900044 ER PT J AU Kobayashi, H Choyke, PL AF Kobayashi, Hisataka Choyke, Peter L. TI Super enhanced permeability and retention (SUPR) effects in tumors following near infrared photoimmunotherapy SO NANOSCALE LA English DT Review ID DRUG-DELIVERY; SOLID TUMORS; IN-VIVO; CANCER; IMPROVEMENT; THERAPY AB To date, the delivery of nano-sized therapeutic agents to cancers largely relies on enhanced permeability and retention (EPR) effects that are caused by the leaky nature of cancer vasculature. However, nano-sized agents delivered in this way have demonstrated limited success in oncology due to the relatively small magnitude of the EPR effect. For achieving superior delivery of nano-sized agents, super-enhanced permeability and retention (SUPR) effects are needed. Near infrared photo-immunotherapy (NIR-PIT) is a recently reported therapy that treats tumors with light therapy and subsequently causes an increase in nano-drug delivery up to 24-fold compared with untreated tumors in which only the EPR effect is present. SUPR effects could enhance delivery into tumor beds of a wide variety of nano-sized agents including particles, antibodies, and protein binding small molecular agents. Therefore, taking advantage of the SUPR effects after NIR-PIT may be a promising avenue to utilize a wide variety of nano-drugs in a highly effective manner. C1 [Kobayashi, Hisataka; Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 19 TC 4 Z9 4 U1 14 U2 20 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2016 VL 8 IS 25 BP 12504 EP 12509 DI 10.1039/c5nr05552k PG 6 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA DP8BE UT WOS:000378722100007 PM 26443992 ER PT J AU Suk, WA Sly, PD AF Suk, William A. Sly, Peter D. TI Ensuring a Bright Future for Children's Environmental Health SO ANNALS OF GLOBAL HEALTH LA English DT Editorial Material C1 [Suk, William A.] NIEHS, Hazardous Subst Res Branch, Superfund Res Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Sly, Peter D.] Univ Queensland, Childrens Hlth & Environm Program, Child Hlth Res Ctr, Brisbane, Qld, Australia. RP Suk, WA (reprint author), NIEHS, Hazardous Subst Res Branch, Superfund Res Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-9996 J9 ANN GLOB HEALTH JI Ann. Glob. Health PD JAN-FEB PY 2016 VL 82 IS 1 BP 1 EP 2 DI 10.1016/j.aogh.2016.01.011 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DO8WU UT WOS:000378067000001 PM 27325062 ER PT J AU Sly, PD Carpenter, DO Van den Berg, M Stein, RT Landrigan, PJ Brune-Drisse, MN Suk, W AF Sly, Peter D. Carpenter, David O. Van den Berg, Martin Stein, Renato T. Landrigan, Philip J. Brune-Drisse, Marie-Noel Suk, William TI Health Consequences of Environmental Exposures: Causal Thinking in Global Environmental Epidemiology SO ANNALS OF GLOBAL HEALTH LA English DT Review DE children; pollution; non-communicable disease; burden of disease; public health ID ENDOCRINE-DISRUPTING CHEMICALS; EARLY-LIFE; SYSTEMATIC ANALYSIS; RISK-FACTORS; DISEASE; BURDEN; MICROBIOTA; ABNORMALITIES; ASSOCIATION; EPIGENETICS AB The 2010 Global Burden of Disease estimates indicate a trend toward increasing years lived with disability from chronic noncommunicable diseases (NCDs). Risk factors examined included smoking, diet, alcohol, drug abuse, and physical inactivity. By contrast, little consideration was given to accumulating evidence that exposures to environmental chemicals, psychosocial stress, and malnutrition during fetal development and across the life span also increase risk of NCDs. To address this gap, we undertook a narrative review of early-life environmental contributions to disease. We documented numerous etiologic associations. We propose that future GBD estimates use an expanded approach for assessing etiologic contributions of environmental exposures to recognized disease risk factors. We argue that broadening the definition of environmental disease, together with improved methods of assessing early life exposures and their health outcomes across the life span, will allow better understanding of causal associations and provide the incentives required to support strategies to control avoidable exposures and reduce disease risk. C1 [Sly, Peter D.] Univ Queensland, Childrens Hlth & Environm Program, Queensland Childrens Med Res Inst, Brisbane, Qld, Australia. [Carpenter, David O.] SUNY Albany, Inst Hlth & Environm, Rensselaer, NY USA. [Van den Berg, Martin] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. [Stein, Renato T.] Pontificia Univ Catolica Rio Grande do Sul, Biomed Res Inst, Ctr Infant, Porto Alegre, RS, Brazil. [Landrigan, Philip J.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Brune-Drisse, Marie-Noel] WHO, Dept Publ Hlth Environm & Social Determinants Hlt, CH-1211 Geneva, Switzerland. [Suk, William] NIEHS, Hazardous Subst Res Branch, Superfund Res Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RP Sly, PD (reprint author), Univ Queensland, Childrens Hlth & Environm Program, Queensland Childrens Med Res Inst, Brisbane, Qld, Australia. EM p.sly@uq.edu.au FU World Health Organization [001] NR 43 TC 2 Z9 2 U1 10 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-9996 J9 ANN GLOB HEALTH JI Ann. Glob. Health PD JAN-FEB PY 2016 VL 82 IS 1 BP 3 EP 9 DI 10.1016/j.aogh.2016.01.004 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DO8WU UT WOS:000378067000002 PM 27325063 ER PT J AU Suk, W Ruchirawat, M Stein, RT Diaz-Barriga, F Carpenter, DO Neira, M Sly, PD AF Suk, William Ruchirawat, Mathuros Stein, Renato T. Diaz-Barriga, Fernando Carpenter, David O. Neira, Maria Sly, Peter D. TI Health Consequences of Environmental Exposures in Early Life: Coping with a Changing World in the Post-MDG Era SO ANNALS OF GLOBAL HEALTH LA English DT Review DE children; noncommunicable disease; social determinants of health; environmental justice; health care systems ID MILLENNIUM DEVELOPMENT GOALS; CLIMATE-CHANGE; GUT MICROBIOTA; CONTAMINANTS; NEWGENERIS; DISEASES; OUTCOMES; RISK AB Despite overall progress toward achieving the Millennium Development Goals, large health discrepancies persist between developed and developing countries. The world is rapidly changing and the influences of societal change and climate change will disproportionately affect the world's most vulnerable populations, thus exacerbating current inequities. Current development strategies do not adequately address these disproportionate impacts of environmental exposures. The aim of this study was to propose a new framework to address the health consequences of environmental exposures beyond 2015. This framework is transdisciplinary and precautionary. It is based on identifying social and economic determinants of health, strengthening primary health systems, and improving the health of vulnerable populations. It incorporates deliberate plans for assessment and control of avoidable environmental exposures. It sets specific, measurable targets for health and environmental improvement. C1 [Suk, William] NIEHS, Hazardous Subst Res Branch, Superfund Res Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Ruchirawat, Mathuros] Chulabhorn Res Inst, Bangkok, Thailand. [Stein, Renato T.] Pontificia Univ Catolica Rio Grande do Sul, Biomed Res Inst, Ctr Infant, Porto Alegre, RS, Brazil. [Diaz-Barriga, Fernando] Univ Autonoma San Luis Potosi, Sch Med, San Luis Potosi, Mexico. [Carpenter, David O.] SUNY Albany, Inst Hlth & Environm, Rensselaer, NY USA. [Neira, Maria] WHO, Dept Publ Hlth Environm & Social Determinants Hlt, CH-1211 Geneva, Switzerland. [Sly, Peter D.] Univ Queensland, Childrens Hlth & Environm Program, Queensland Childrens Med Res Inst, Brisbane, Qld, Australia. RP Sly, PD (reprint author), Univ Queensland, Childrens Hlth & Environm Program, Queensland Childrens Med Res Inst, Brisbane, Qld, Australia. EM p.sly@uq.edu.au FU World Health Organization [001] NR 43 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-9996 J9 ANN GLOB HEALTH JI Ann. Glob. Health PD JAN-FEB PY 2016 VL 82 IS 1 BP 20 EP 27 DI 10.1016/j.aogh.2016.01.006 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DO8WU UT WOS:000378067000004 PM 27325065 ER PT J AU Zheng, TZ Zhang, J Sommer, K Bassig, BA Zhang, XC Braun, J Xu, SQ Boyle, P Zhang, B Shi, KC Buka, S Liu, SM Li, YY Qian, ZM Dai, M Romano, M Zou, AF Kelsey, K AF Zheng, Tongzhang Zhang, Jie Sommer, Kathryn Bassig, Bryan A. Zhang, Xichi Braun, Jospeh Xu, Shuangqing Boyle, Peter Zhang, Bin Shi, Kunchong Buka, Stephen Liu, Siming Li, Yuanyuan Qian, Zengmin Dai, Min Romano, Megan Zou, Aifen Kelsey, Karl TI Effects of Environmental Exposures on Fetal and Childhood Growth Trajectories SO ANNALS OF GLOBAL HEALTH LA English DT Review DE prenatal exposure; environmental pollutants; fetal growths; adverse birth outcomes; low birth weight; catch-up growth; child development ID LOW-BIRTH-WEIGHT; AMBIENT AIR-POLLUTION; UMBILICAL-CORD BLOOD; LOS-ANGELES-COUNTY; POLYBROMINATED DIPHENYL ETHERS; FINE PARTICULATE MATTER; POLYCYCLIC AROMATIC-HYDROCARBONS; PERFLUOROOCTANOIC ACID EXPOSURE; ADVERSE PREGNANCY OUTCOMES; CATCH-UP GROWTH AB Delayed fetal growth and adverse birth outcomes are some of the greatest public health threats to this generation of children worldwide because these conditions are major determinants of mortality, morbidity, and disability in infancy and childhood and are also associated with diseases in adult life. A number of studies have investigated the impacts of a range of environmental conditions during pregnancy (including air pollution, endocrine disruptors, persistent organic pollutants, heavy metals) on fetal and child development. The results, while provocative, have been largely inconsistent. This review summarizes up to date epidemiologic studies linking major environmental pollutants to fetal and child development and suggested future directions for further investigation. C1 [Zheng, Tongzhang; Zhang, Jie; Braun, Jospeh; Shi, Kunchong; Buka, Stephen; Liu, Siming; Li, Yuanyuan; Romano, Megan; Kelsey, Karl] Brown Sch Publ Hlth, Dept Epidemiol, Providence, RI USA. [Sommer, Kathryn] Haverford Coll, Haverford, PA 19041 USA. [Bassig, Bryan A.] NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. [Zhang, Xichi] George Washington Univ, Washington, DC USA. [Xu, Shuangqing; Li, Yuanyuan] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Sch Publ Hlth, Wuhan 430074, Hubei, Peoples R China. [Boyle, Peter] Int Prevent Res Inst, Lyon, France. [Zhang, Bin; Zou, Aifen] Wuhan Med & Hlth Ctr Women & Children, Wuhan, Hubei, Peoples R China. [Qian, Zengmin] St Louis Univ, Coll Publ Hlth & Social Justice, St Louis, MO 63103 USA. [Dai, Min] Chinese Acad Med Sci, China Natl Canc Ctr, Beijing 100730, Peoples R China. RP Zheng, TZ (reprint author), Brown Sch Publ Hlth, Dept Epidemiol, Providence, RI USA. EM tongzhang_zheng@brown.edu RI Boyle, Peter/A-4380-2014 OI Boyle, Peter/0000-0001-6251-0610 FU FIC NIH HHS [D43 TW007864, D43 TW008323] NR 263 TC 1 Z9 1 U1 5 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-9996 J9 ANN GLOB HEALTH JI Ann. Glob. Health PD JAN-FEB PY 2016 VL 82 IS 1 BP 41 EP 99 DI 10.1016/j.aogh.2016.01.008 PG 59 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DO8WU UT WOS:000378067000006 PM 27325067 ER PT J AU Cao, JJ Xu, XJ Hylkema, MN Zeng, EY Sly, PD Suk, WA Bergman, A Huo, X AF Cao, Junjun Xu, Xijin Hylkema, Machteld N. Zeng, Eddy Y. Sly, Peter D. Suk, William A. Bergman, Ake Huo, Xia TI Early-life Exposure to Widespread Environmental Toxicants and Health Risk: A Focus on the Immune and Respiratory Systems SO ANNALS OF GLOBAL HEALTH LA English DT Review DE early-life exposure; heavy metals; tobacco smoke; persistent organic pollutants; immune development; lung ID TOBACCO-SMOKE EXPOSURE; IN-UTERO EXPOSURE; DEVELOPING RAT LUNG; MATERNAL SMOKING; POLYCHLORINATED-BIPHENYLS; PRENATAL EXPOSURE; ARSENIC EXPOSURE; CORD BLOOD; POSTNATAL EXPOSURE; PERINATAL EXPOSURE AB Evidence has accumulated that exposure to widespread environmental toxicants, such as heavy metals, persistent organic pollutants, and tobacco smoke adversely affect fetal development and organ maturation, even after birth. The developing immune and respiratory systems are more sensitive to environmental toxicants due to their long-term physical development, starting from the early embryonic stage and persisting into early postnatal life, which requires complex signaling pathways that control proliferation and differentiation of highly heterogeneous cell types. In this review, we summarize the effect of early-life exposure to several widespread environmental toxicants on immune and lung development before and after birth, including the effects on immune cell counts, baseline characteristics of cell-mediated and humoral immunity, and alteration of lung structure and function in offspring. We also review evidence supporting the association between early-life exposure to environmental toxicants and risk for immune-related diseases and lung dysfunction in offspring in later life. C1 [Cao, Junjun; Xu, Xijin] Shantou Univ, Coll Med, Lab Environm Med & Dev Toxicol, Shantou, Peoples R China. [Cao, Junjun; Hylkema, Machteld N.] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Groningen, Netherlands. [Cao, Junjun; Hylkema, Machteld N.] Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Groningen, Netherlands. [Zeng, Eddy Y.; Huo, Xia] Jinan Univ, Sch Environm, Guangzhou Key Lab Environm Exposure & Hlth, Guangdong Key Lab Environm Pollut & Hlth, Guangzhou, Guangdong, Peoples R China. [Sly, Peter D.] Univ Queensland, Childrens Hlth & Environm Program, Child Hlth Res Ctr, Brisbane, Qld 4072, Australia. [Suk, William A.] NIEHS, Hazardous Subst Res Branch, Superfund Res Program, NIH, Bethesda, MD USA. [Bergman, Ake] Swedish Toxicol Sci Res Ctr Swetox, Sodertalje, Sweden. RP Huo, X (reprint author), Jinan Univ, Sch Environm, Guangzhou Key Lab Environm Exposure & Hlth, Guangdong Key Lab Environm Pollut & Hlth, Guangzhou, Guangdong, Peoples R China. EM xhuo@jnu.edu.cn FU Natural Science Foundation of China, NSFC [21577084, 21377077] FX This work was supported by the Natural Science Foundation of China, NSFC ( 21577084, 21377077). NR 121 TC 3 Z9 3 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-9996 J9 ANN GLOB HEALTH JI Ann. Glob. Health PD JAN-FEB PY 2016 VL 82 IS 1 BP 119 EP 131 DI 10.1016/j.aogh.2016.01.023 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DO8WU UT WOS:000378067000009 PM 27325070 ER PT J AU Elghouche, A Shokri, T Qin, YW Wargo, S Citrin, D Van Waes, C AF Elghouche, Alhasan Shokri, Tom Qin, Yewen Wargo, Susannah Citrin, Deborah Van Waes, Carter TI Unilateral Cervical Polyneuropathies following Concurrent Bortezomib, Cetuximab, and Radiotherapy for Head and Neck Cancer SO CASE REPORTS IN OTOLARYNGOLOGY LA English DT Article ID INDUCED PERIPHERAL NEUROPATHY; BRACHIAL PLEXOPATHY; BREAST-CANCER; MULTIPLE-MYELOMA; RADIATION; PLEXUS; INHIBITION; CARCINOMA; THERAPY; GENES AB We report a constellation of cervical polyneuropathies in a patient treated with concurrent bortezomib, cetuximab, and cisplatin alongside intensity modulated radiotherapy for carcinoma of the tonsil with neck metastasis. The described deficits include brachial plexopathy, cervical sensory neuropathy, and oculosympathetic, recurrent laryngeal, and phrenic nerve palsies within the ipsilateral radiation field. Radiation neuropathy involving the brachial plexus is typically associated with treatment of breast or lung cancer; however, increased awareness of this entity in the context of investigational agents with potential neuropathic effects in head and neck cancer has recently emerged. With this report, we highlight radiation neuropathy in the setting of investigational therapy for head and neck cancer, particularly since these sequelae may present years after therapy and entail significant and often irreversible morbidity. C1 [Elghouche, Alhasan] Indiana Univ Sch Med, 1120 W Michigan St,Suite 200, Indianapolis, IN 46202 USA. [Shokri, Tom] Penn State Milton S Hershey Med Ctr, Div Otolaryngol, 100 Campus Dr,Suite 400, Hershey, PA 17033 USA. [Qin, Yewen] Kings Coll London, Sch Med, London WC2R 2LS, England. [Wargo, Susannah; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Citrin, Deborah] NCI, Radiat Oncol Branch, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Elghouche, A (reprint author), Indiana Univ Sch Med, 1120 W Michigan St,Suite 200, Indianapolis, IN 46202 USA. EM aelghouc@iupui.edu NR 25 TC 1 Z9 1 U1 1 U2 1 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2090-6765 EI 2090-6773 J9 CASE REP OTOLARYNGOL JI Case Rep. Otolaryngol. PY 2016 AR 2313714 DI 10.1155/2016/2313714 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA DP2HU UT WOS:000378309900001 ER PT J AU Vasilev, KV Gallo, E Shank, N Jarvik, JW AF Vasilev, Kalin V. Gallo, Eugenio Shank, Nathaniel Jarvik, Jonathan W. TI Novel Biosensor of Membrane Protein Proximity Based on Fluorogen Activated Proteins SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING LA English DT Article DE Membrane proteins; protein interaction; protein proximity; biosensor; fluorogen-activating protein; tethered fluorogen assay; TEFLA ID CELL-SURFACE PROTEINS; TERNARY COMPLEX; LIVING CELLS; FRET; MICROSCOPY; DOMAINS AB We describe a novel biosensor system for reporting proximity between cell surface proteins in live cultured cells. The biosensor takes advantage of recently developed fluorogen-activating proteins (FAPs) that display fluorescence only when bound to otherwise-nonfluorescent fluorogen molecules. To demonstrate feasibility for the approach, two recombinant rapamycin-binding proteins were expressed as single-pass plasma membrane proteins in HeLa cells; one of the proteins (scAvd-FRB) carried an extracellular avidin tag; the other (HL1-TO1-FKBP) carried an extracellular FAP. Cells were incubated with a membrane-impermeable bivalent ligand (biotin-PEG2000-DIR) consisting of biotin joined to a dimethyl-indole red (DIR) fluorogen by a polyethylene glycol linker, thus tethering the fluorogen to the scAvd-FRB fusion protein. Addition of rapamycin, which promotes FKBP-FRB dimerization and thereby brings the FAP in close proximity to the tethered fluorogen, led to a significant increase in DIR fluorescence. We call the new proximity assay TEFLA, for tethered fluorogen assay. C1 [Vasilev, Kalin V.; Gallo, Eugenio; Jarvik, Jonathan W.] Carnegie Mellon Univ, Dept Biol Sci, 4400 5th Ave, Pittsburgh, PA 15213 USA. [Shank, Nathaniel] Carnegie Mellon Univ, Dept Chem, 4400 5th Ave, Pittsburgh, PA 15213 USA. [Vasilev, Kalin V.; Gallo, Eugenio; Shank, Nathaniel; Jarvik, Jonathan W.] Carnegie Mellon Univ, Mol Biosensor & Imaging Ctr, Pittsburgh, PA 15213 USA. [Gallo, Eugenio] Univ Toronto, Banting & Best Dept Med Res, Donnelly Ctr, Toronto, ON, Canada. [Gallo, Eugenio] Univ Toronto, Dept Mol Genet, Donnelly Ctr, Toronto, ON, Canada. [Shank, Nathaniel] NIDDK, LBC Synthet Bioact Mol Sect, NIH, Bethesda, MD 20892 USA. RP Jarvik, JW (reprint author), Carnegie Mellon Univ, 4400 Fifth Ave, Pittsburgh, PA 15213 USA. EM jarvik@cmu.edu FU National Institutes of Health Common Fund [U54 GM103529] FX We thank Yehuda Creeger and Haibing Teng for instrument training and assistance (flow-cytometry and confocal microscopy respectively). Funding came from the National Institutes of Health Common Fund, grant U54 GM103529. NR 18 TC 0 Z9 0 U1 2 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1386-2073 EI 1875-5402 J9 COMB CHEM HIGH T SCR JI Comb. Chem. High Throughput Screen PY 2016 VL 19 IS 5 BP 392 EP 399 DI 10.2174/1386207319666160408150320 PG 8 WC Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA DO8SQ UT WOS:000378054400008 PM 27055753 ER PT J AU Nussinov, R Muratcioglu, S Tsai, CJ Jang, H Gursoy, A Keskin, O AF Nussinov, Ruth Muratcioglu, Serena Tsai, Chung-Jung Jang, Hyunbum Gursoy, Attila Keskin, Ozlem TI K-Ras4B/calmodulin/PI3Ka: A promising new adenocarcinoma-specific drug target? SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE KRAS; allosteric drugs; calmodulin; colorectal cancer; lung cancer; calcium; K-Ras dimers; KRAS4A; KRAS4B; pancreatic cancer; pancreatic ductal adenocarcinomas (PDAC); orthosteric drugs; small molecule drug ID PROTEIN-PROTEIN INTERACTIONS; CELL LUNG-CANCER; PANCREATIC INTRAEPITHELIAL NEOPLASIA; SMALL GTPASE K-RAS4B; HUMAN-COLON-CANCER; K-RAS 4A; COLORECTAL-CANCER; ONCOGENIC KRAS; PHOSPHOINOSITIDE 3-KINASE; DUCTAL ADENOCARCINOMA AB Introduction: Decades of efforts have yet to yield a safe and effective drug to target KRAS-driven pancreatic, colorectal and lung cancers; particularly those driven by the highly oncogenic splice variant KRAS4B. K-Ras4B's fairly smooth surface, cancer tissue/cell heterogeneity, tolerated lipid post-translational modification exchange, as well as drug-elicited toxicity present a daunting challenge. Areas covered: Within this framework, hee we focus on a new adenocarcinoma-specific drug concept. Calmodulin (CaM) binds to K-Ras4B but not to the H-Ras or N-Ras isoforms. Physiologically, in calcium- and calmodulin-rich environments such as ductal tissues, calmodulin can sequester K-Ras4B from the membrane; in cancer, CaM/Ca2+ can replace the missing receptor tyrosine kinase (RTK) signal, acting to fully activate PI3K alpha. Expert opinion: An oncogenic GTP-bound K-Ras4B/CaM/PI3K alpha complex is supported by available experimental and clinical data; therefore, targeting it may address a pressing therapeutic need. High resolution electron microscopy (EM) or crystal structure of the tripartite complex would allow orthosteric or allosteric drug discovery to disrupt the CaM/PI3K alpha interface and thus Akt/mTOR signaling. However, since drug resistance is expected to develop, combining it with compensatory pathways, particularly those involved in cell-cycle control, appears a reasonable strategy. C1 [Nussinov, Ruth; Tsai, Chung-Jung; Jang, Hyunbum] NCI, Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. [Muratcioglu, Serena; Keskin, Ozlem] Koc Univ, Dept Chem & Biol Engn, Istanbul, Turkey. [Gursoy, Attila] Koc Univ, Dept Comp Engn, Istanbul, Turkey. RP Nussinov, R (reprint author), NCI, Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD USA. EM nussinor@helix.nih.gov RI Gursoy, Attila/E-9565-2015 OI Gursoy, Attila/0000-0002-2297-2113 FU Frederick National Laboratory for Cancer Research, National Institutes of Health (NIH) [HHSN261200800001E]; Scientific and Technological Research Council of Turkey (TUBITAK) under TUBITAK Research Grant [114M196] FX The authors were supported in part by Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health (NIH), under contract HHSN261200800001E awarded to R Nussinov. The authors were also supported by the Scientific and Technological Research Council of Turkey (TUBITAK) under TUBITAK Research Grant No. 114M196 awarded to O Keskin. 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. 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 140 TC 3 Z9 3 U1 3 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1472-8222 EI 1744-7631 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PY 2016 VL 20 IS 7 BP 831 EP 842 DI 10.1517/14728222.2016.1135131 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DP1OI UT WOS:000378258900006 PM 26873344 ER PT J AU Chopra, A Jung, M Kaplan, RC Appel, DW Dinces, EA Dhar, S Zee, PC Gonzalez, F Lee, DJ Ramos, AR Hoffman, HJ Redline, S Cruickshanks, KJ Shah, NA AF Chopra, Amit Jung, Molly Kaplan, Robert C. Appel, David W. Dinces, Elizabeth A. Dhar, Sumitrajit Zee, Phyllis C. Gonzalez, Franklyn, II Lee, David J. Ramos, Alberto R. Hoffman, Howard J. Redline, Susan Cruickshanks, Karen J. Shah, Neomi A. TI Sleep Apnea Is Associated with Hearing Impairment: The Hispanic Community Health Study/Study of Latinos SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE sleep apnea; hearing impairment ID NUTRITION EXAMINATION SURVEY; UNITED-STATES; OLDER-ADULTS; RISK-FACTORS; DISEASE; DEATH; PREVALENCE; PATHWAYS; DEMENTIA; EVENTS AB Study Objective: Sleep apnea (SA) may promote hearing impairment (HI) through ischemia and inflammation of the cochlea. Our objective was to assess an independent association between SA and HI in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants. Methods: We used data from the HCHS/SOL, a multicenter population-based study of self-identifying Hispanic/Latinos 18-to 74-y-old adults from four US urban communities. We performed home SA testing and in-clinic audiometry testing in all participants. SA was defined as an apnea-hypopnea index (AHI) >= 15 events/h. HI was defined as a mean hearing threshold > 25 dB hearing level in either ear at the frequencies: 3,000 to 8,000 Hz for high-frequency HI (HF-HI) and 500 to 2,000 Hz for low-frequency HI (LF-HI). Combined-frequency HI (CF-HI) was defined as both conditions present, and Any-HI was considered as HI in either low or high frequencies. Results: Of 13,967 participants, 9.9% had SA and 32.3% had Any-HI. Adjusted for risk factors for HI, those with SA had a 30% higher odds of Any-HI (95% confidence interval [CI] = 8% to 57%), 26% higher odds of HF-HI (CI = 3% to 55%), 127% higher odds of LF-HI (CI = 21% to 326%), and 29% higher odds of CF-HI (CI = 0% to 65%). A dose-response association was observed between AHI severity and Any-HI (versus no SA, OR for AHI = 15 and < 30 = 1.22, CI = 0.96 to 1.54, and OR for AHI = 30 = 1.46, CI = 1.11 to 1.91, p = 0.002). Conclusion: SA is associated with HF-HI and LF-HI, independent of snoring and other confounders. C1 [Chopra, Amit] Albany Med Ctr Hosp, Albany, NY 12208 USA. [Jung, Molly; Kaplan, Robert C.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Appel, David W.; Dinces, Elizabeth A.] Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA. [Dhar, Sumitrajit; Zee, Phyllis C.] Northwestern Univ, Evanston, IL USA. [Gonzalez, Franklyn, II] Univ N Carolina, Chapel Hill, NC USA. [Lee, David J.; Ramos, Alberto R.] Univ Miami, Miami, FL USA. [Hoffman, Howard J.] NIDCD, NIH, Bethesda, MD USA. [Redline, Susan] Harvard Univ, Sch Med, Boston, MA USA. [Cruickshanks, Karen J.] Univ Wisconsin, Madison, WI USA. [Shah, Neomi A.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. RP Chopra, A (reprint author), Albany Med Coll, Dept Med, Div Pulm & Crit Care Med, Med, MC-91,47 New Scotland Ave, Albany, NY 12208 USA. EM chopraa1@mail.amc.edu FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC65233, N01-HC65234, N01-HC65235, N01-HC65236, N01-HC65237]; National Institute on Minority Health and Health Disparities; National Institute on Deafness and Other Communication Disorders; National Institute of Dental and Craniofacial Research; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Neurological Disorders and Stroke; NIH Institution-Office of Dietary Supplements; Jazz FX The Hispanic Community Health Study/Study of Latinos was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements. Dr. Redline has received grant/research funds from Jazz. Dr. Ramos has consulted for MCMC, LLC, MRioA, Inc, and Comppartners. Dr. Zee has consulted for Merck, Vanda, Jazz, and Philips and is a stock holder of Teva. The other authors have indicated no financial conflicts of interest. NR 38 TC 1 Z9 1 U1 6 U2 9 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2016 VL 12 IS 5 BP 719 EP 726 DI 10.5664/jcsm.5804 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DP2QD UT WOS:000378333300015 PM 26951413 ER PT S AU Castro, MA Williford, JP Cota, MR MacLaren, JM Dardzinski, BJ Latour, LL Pham, DL Butman, JA AF Castro, Marcelo A. Williford, Joshua P. Cota, Martin R. MacLaren, Judy M. Dardzinski, Bernard J. Latour, Lawrence L. Pham, Dzung L. Butman, John A. BE Gimi, B Krol, A TI Quantification of traumatic meningeal injury using Dynamic Contrast Enhanced (DCE) Fluid-Attenuated Inversion Recovery (FLAIR) imaging SO MEDICAL IMAGING 2016-BIOMEDICAL APPLICATIONS IN MOLECULAR, STRUCTURAL, AND FUNCTIONAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT SPIE Biomedical Applications in Molecular, Structural and Functional Imaging Conference CY MAR 01-03, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, imXPAD DE Traumatic meningeal injury; Traumatic brain injury; Dynamic Contrast Enhanced (DCE) Magnetic Resonance Imaging (MRI); Fluid-Attenuated Inversion Recovery (FLAIR); Image registration ID BRAIN-INJURY; HEAD-INJURY; SEQUELAE AB Traumatic meningeal injury is a novel imaging marker of traumatic brain injury, which appears as enhancement of the dura on post-contrast T2-weighted FLAIR images, and is likely associated with inflammation of the meninges. Dynamic Contrast Enhanced MRI provides a better discrimination of abnormally perfused regions. A method to properly identify those regions is presented. Images of seventeen patients scanned within 96 hours of head injury with positive traumatic meningeal injury were normalized and aligned. The difference between the pre- and last post-contrast acquisitions was segmented and voxels in the higher class were spatially clustered. Spatial and morphological descriptors were used to identify the regions of enhancement: a) centroid; b) distance to the brain mask from external voxels; c) distance from internal voxels; d) size; e) shape. The method properly identified thirteen regions among all patients. The method failed in one case due to the presence of a large brain lesion that altered the mask boundaries. Most false detections were correctly rejected resulting in a sensitivity and specificity of 92.9% and 93.6%, respectively. C1 [Castro, Marcelo A.; Williford, Joshua P.; Cota, Martin R.; Dardzinski, Bernard J.; Latour, Lawrence L.; Pham, Dzung L.] Henry M Jackson Fdn, Ctr Neurosci & Regenerat Med, 9000 Rockville Pike, Bethesda, MD USA. [MacLaren, Judy M.] Johns Hopkins Suburban Hosp, Old Georgetown Rd, Bethesda, MD USA. [Dardzinski, Bernard J.] Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, Bethesda, MD 20814 USA. [Butman, John A.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, 9000 Rockville Pike, Bethesda, MD USA. [Latour, Lawrence L.] NINDS, Stroke Diagnost & Therapeut Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Castro, MA (reprint author), Henry M Jackson Fdn, Ctr Neurosci & Regenerat Med, 9000 Rockville Pike, Bethesda, MD USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0023-2 J9 PROC SPIE PY 2016 VL 9788 AR 97882P DI 10.1117/12.2216902 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE9WB UT WOS:000378223800090 ER PT S AU Cheng, RD Jackson, JN McCreedy, ES Gandler, W Eijkenboom, JJFA van Middelkoop, M McAuliffe, MJ Sheehan, FT AF Cheng, Ruida Jackson, Jennifer N. McCreedy, Evan S. Gandler, William Eijkenboom, J. J. F. A. van Middelkoop, M. McAuliffe, Matthew J. Sheehan, Frances T. BE Gimi, B Krol, A TI Patellar Segmentation from 3D Magnetic Resonance Images Using Guided Recursive Ray-tracing for Edge Pattern Detection SO MEDICAL IMAGING 2016-BIOMEDICAL APPLICATIONS IN MOLECULAR, STRUCTURAL, AND FUNCTIONAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT SPIE Biomedical Applications in Molecular, Structural and Functional Imaging Conference CY MAR 01-03, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, imXPAD DE knee segmentation; pattern detection; recursive ray-tracing; depth first search ID SHAPE; BONE AB The paper presents an automatic segmentation methodology for the patellar bone, based on 3D gradient recalled echo and gradient recalled echo with fat suppression magnetic resonance images. Constricted search space outlines are incorporated into recursive ray-tracing to segment the outer cortical bone. A statistical analysis based on the dependence of information in adjacent slices is used to limit the search in each image to between an outer and inner search region. A section based recursive ray-tracing mechanism is used to skip inner noise regions and detect the edge boundary. The proposed method achieves higher segmentation accuracy (0.23mm) than the current state-of-the-art methods with the average dice similarity coefficient of 96.0% (SD 1.3%) agreement between the auto-segmentation and ground truth surfaces. C1 [Cheng, Ruida; McCreedy, Evan S.; Gandler, William; McAuliffe, Matthew J.] NIH, Imaging Sci Lab, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. [Jackson, Jennifer N.; Sheehan, Frances T.] NIH, Funct & Appl Biomech Sect, Rehabil Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Eijkenboom, J. J. F. A.; van Middelkoop, M.] Eramus MC, Rotterdam, Netherlands. RP Cheng, RD (reprint author), NIH, Imaging Sci Lab, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0023-2 J9 PROC SPIE PY 2016 VL 9788 AR 97880C DI 10.1117/12.2217232 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE9WB UT WOS:000378223800012 ER PT S AU Pourmorteza, A Siewerdsen, JH Stayman, JW AF Pourmorteza, A. Siewerdsen, J. H. Stayman, J. W. BE Kontos, D Flohr, TG Lo, JY TI A Generalized Fourier Penalty in Prior-Image-Based Reconstruction for Cross-Platform Imaging SO MEDICAL IMAGING 2016: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Physics of Medical Imaging CY FEB 28-MAR 02, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD, Carestream Hlth Inc, GE Healthcare ID CONE-BEAM CT AB Sequential CT studies present an excellent opportunity to apply prior-image-based reconstruction (PIBR) methods that leverage high-fidelity prior imaging studies to improve image quality and/or reduce x-ray exposure in subsequent studies. One major obstacle in using PIBR is that the initial and subsequent studies are often performed on different scanners (e.g. diagnostic CT followed by CBCT for interventional guidance); this results in mismatch in attenuation values due to hardware and software differences. While improved artifact correction techniques can potentially mitigate such differences, the correction is often incomplete. Here, we present an alternate strategy where the PIBR itself is used to mitigate these differences. We define a new penalty for the previously introduced PIBR called Reconstruction of Difference (RoD). RoD differs from many other PIBRs in that it reconstructs only changes in the anatomy (vs. reconstructing the current anatomy). Direct regularization of the difference image in RoD provides an opportunity to selectively penalize spatial frequencies of the difference image (e.g. low frequency differences associated with attenuation offsets and shading artifacts) without interfering with the variations in unchanged background image. We leverage this flexibility and introduce a novel regularization strategy using a generalized Fourier penalty within the RoD framework and develop the modified reconstruction algorithm. We evaluate the performance of the new approach in both simulation studies and in physical CBCT test-bench data. We find that generalized Fourier penalty can be highly effective in reducing low-frequency x-ray artifacts through selective suppression of spatial frequencies in the reconstructed difference image. C1 [Pourmorteza, A.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Siewerdsen, J. H.; Stayman, J. W.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. RP Stayman, JW (reprint author), Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. EM web.stayman@jhu.edu NR 15 TC 0 Z9 0 U1 3 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0018-8 J9 PROC SPIE PY 2016 VL 9783 AR 978319 DI 10.1117/12.2216151 PG 6 WC Optics; Physics, Multidisciplinary; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BE9YS UT WOS:000378352900043 ER PT J AU Stoll, BJ Hansen, NI Bell, EF Walsh, MC Carlo, WA Shankaran, S Laptook, AR Sanchez, PJ Van Meurs, KP Wyckoff, M Das, A Hale, EC Ball, MB Newman, NS Schibler, K Poindexter, BB Kennedy, KA Cotten, CM Watterberg, KL D'Angio, CT DeMauro, SB Truog, WE Devaskar, U Higgins, RD AF Stoll, Barbara J. Hansen, Nellie I. Bell, Edward F. Walsh, Michele C. Carlo, Waldemar A. Shankaran, Seetha Laptook, Abbot R. Sanchez, Pablo J. Van Meurs, Krisa P. Wyckoff, Myra Das, Abhik Hale, Ellen C. Ball, M. Bethany Newman, Nancy S. Schibler, Kurt Poindexter, Brenda B. Kennedy, Kathleen A. Cotten, C. Michael Watterberg, Kristi L. D'Angio, Carl T. DeMauro, Sara B. Truog, William E. Devaskar, Uday Higgins, Rosemary D. CA Eunice Kennedy Shriver Natl Inst TI Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012 EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Stoll, Barbara J.; Hale, Ellen C.] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA 30303 USA. [Hansen, Nellie I.] RTI Int, Social Stat & Environm Sci Unit, Res Triangle Pk, NC USA. [Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Walsh, Michele C.; Newman, Nancy S.] Case Western Reserve Univ, Dept Pediat, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. [Carlo, Waldemar A.] Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA. [Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. [Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA. [Sanchez, Pablo J.] Ohio State Univ, Dept Pediat, Ctr Perinatal Res, Nationwide Childrens Hosp, Columbus, OH 43210 USA. [Van Meurs, Krisa P.; Ball, M. Bethany] Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med, Stanford, CA 94305 USA. [Van Meurs, Krisa P.; Ball, M. Bethany] Lucile Packard Childrens Hosp, Palo Alto, CA USA. [Wyckoff, Myra] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Das, Abhik] RTI Int, Social Stat & Environm Sci Unit, Rockville, MD USA. [Schibler, Kurt] Cincinnati Childrens Hosp Med Ctr, Perinatal Inst, Cincinnati, OH 45229 USA. [Poindexter, Brenda B.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. [Kennedy, Kathleen A.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA. [Cotten, C. Michael] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Watterberg, Kristi L.] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [D'Angio, Carl T.] Univ Rochester, Sch Med & Dent, Rochester, NY 14627 USA. [DeMauro, Sara B.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. [Truog, William E.] Childrens Mercy Hosp, Dept Pediat, Kansas City, MO 64108 USA. [Devaskar, Uday] Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Stoll, BJ (reprint author), Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA 30303 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD JAN PY 2016 VL 71 IS 1 BP 7 EP 9 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DP0JD UT WOS:000378175200004 ER PT S AU Miller, S AF Miller, Sheldon BE Chan, CC TI Animal Models of Ophthalmic Diseases Foreword SO ANIMAL MODELS OF OPHTHALMIC DISEASES SE Essentials in Ophthalmology LA English DT Editorial Material; Book Chapter C1 [Miller, Sheldon] NEI, NIH, Bethesda, MD 20892 USA. RP Miller, S (reprint author), NEI, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1612-3212 BN 978-3-319-19434-9; 978-3-319-19433-2 J9 ESSENT OPHTHALMOL PY 2016 BP V EP VI D2 10.1007/978-3-319-19434-9 PG 2 WC Ophthalmology SC Ophthalmology GA BE8ET UT WOS:000376387400001 ER PT S AU Chan, CC AF Chan, Chi-Chao BE Chan, CC TI Animal Models of Ophthalmic Diseases Preface SO ANIMAL MODELS OF OPHTHALMIC DISEASES SE Essentials in Ophthalmology LA English DT Editorial Material; Book Chapter C1 [Chan, Chi-Chao] NEI, NIH, Bethesda, MD 20892 USA. [Chan, Chi-Chao] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China. RP Chan, CC (reprint author), NEI, NIH, Bethesda, MD 20892 USA.; Chan, CC (reprint author), Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1612-3212 BN 978-3-319-19434-9; 978-3-319-19433-2 J9 ESSENT OPHTHALMOL PY 2016 BP VII EP X D2 10.1007/978-3-319-19434-9 PG 4 WC Ophthalmology SC Ophthalmology GA BE8ET UT WOS:000376387400002 ER PT S AU Johnson, TV Tomarev, SI AF Johnson, Thomas V. Tomarev, Stanislav I. BE Chan, CC TI Animal Models of Glaucoma SO ANIMAL MODELS OF OPHTHALMIC DISEASES SE Essentials in Ophthalmology LA English DT Article; Book Chapter ID OPEN-ANGLE GLAUCOMA; RETINAL GANGLION-CELLS; NORMAL-TENSION GLAUCOMA; OPTIC-NERVE DAMAGE; ELEVATED INTRAOCULAR-PRESSURE; INDUCED OCULAR HYPERTENSION; TRABECULAR MESHWORK CELLS; CLASSICAL COMPLEMENT CASCADE; PRIMARY CONGENITAL GLAUCOMA; GENOME-WIDE ASSOCIATION C1 [Tomarev, Stanislav I.] NEI, Sect Retinal Gangl Cell Biol, Lab Retinal Cell & Mol Biol, NIH, 6 Ctr Dr,MSC 0608,Bldg 6,Room 212, Bethesda, MD 20892 USA. [Johnson, Thomas V.] Johns Hopkins Univ Hosp, Wilmer Eye Inst, 600 N Wolfe St,Wilmer B-29, Baltimore, MD 21287 USA. RP Tomarev, SI (reprint author), NEI, Sect Retinal Gangl Cell Biol, Lab Retinal Cell & Mol Biol, NIH, 6 Ctr Dr,MSC 0608,Bldg 6,Room 212, Bethesda, MD 20892 USA. EM tomarevs@nei.nih.gov RI Johnson, Thomas/C-9351-2011 OI Johnson, Thomas/0000-0002-5372-5457 NR 156 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1612-3212 BN 978-3-319-19434-9; 978-3-319-19433-2 J9 ESSENT OPHTHALMOL PY 2016 BP 31 EP 49 DI 10.1007/978-3-319-19434-9_3 D2 10.1007/978-3-319-19434-9 PG 19 WC Ophthalmology SC Ophthalmology GA BE8ET UT WOS:000376387400007 ER PT S AU Chew, EY AF Chew, Emily Y. BE Chan, CC TI Animal Models of Age-Related Macular Degeneration: Subretinal Inflammation Commentary SO ANIMAL MODELS OF OPHTHALMIC DISEASES SE Essentials in Ophthalmology LA English DT Editorial Material; Book Chapter C1 [Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Chew, EY (reprint author), NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. EM echew@nei.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1612-3212 BN 978-3-319-19434-9; 978-3-319-19433-2 J9 ESSENT OPHTHALMOL PY 2016 BP 63 EP 64 D2 10.1007/978-3-319-19434-9 PG 2 WC Ophthalmology SC Ophthalmology GA BE8ET UT WOS:000376387400010 ER PT S AU Wong, WT AF Wong, Wai T. BE Chan, CC TI Animal Models of Age-Related Macular Degeneration: Subretinal Inflammation Commentary SO ANIMAL MODELS OF OPHTHALMIC DISEASES SE Essentials in Ophthalmology LA English DT Editorial Material; Book Chapter C1 [Wong, Wai T.] NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bethesda, MD 20892 USA. RP Wong, WT (reprint author), NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bethesda, MD 20892 USA. EM wongw@nei.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1612-3212 BN 978-3-319-19434-9; 978-3-319-19433-2 J9 ESSENT OPHTHALMOL PY 2016 BP 64 EP 65 D2 10.1007/978-3-319-19434-9 PG 2 WC Ophthalmology SC Ophthalmology GA BE8ET UT WOS:000376387400011 ER PT S AU Kielczewski, JL Caspi, RR AF Kielczewski, Jennifer L. Caspi, Rachel R. BE Chan, CC TI Animal Models of Autoimmune Uveitis SO ANIMAL MODELS OF OPHTHALMIC DISEASES SE Essentials in Ophthalmology LA English DT Article; Book Chapter ID RETINAL-PIGMENT EPITHELIUM; ENDOTOXIN-INDUCED UVEITIS; OCULAR IMMUNE PRIVILEGE; REGULATORY T-CELLS; II TRANSGENIC MICE; NEO-SELF ANTIGEN; ANTERIOR UVEITIS; MOUSE MODEL; DISEASE; PROTEIN C1 [Caspi, Rachel R.] NEI, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 10N222, Bethesda, MD 20892 USA. [Kielczewski, Jennifer L.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 10N222, Bethesda, MD 20892 USA. EM nussenblattr@nei.nih.gov; rcaspi@helix.nih.gov NR 64 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1612-3212 BN 978-3-319-19434-9; 978-3-319-19433-2 J9 ESSENT OPHTHALMOL PY 2016 BP 85 EP 99 DI 10.1007/978-3-319-19434-9_6 D2 10.1007/978-3-319-19434-9 PG 15 WC Ophthalmology SC Ophthalmology GA BE8ET UT WOS:000376387400014 ER PT S AU Sieving, PA AF Sieving, Paul A. BE Chan, CC TI Animal Models of Retinitis Pigmentosa (RP) Commentary SO ANIMAL MODELS OF OPHTHALMIC DISEASES SE Essentials in Ophthalmology LA English DT Editorial Material; Book Chapter C1 [Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA. RP Sieving, PA (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM pas@NEI.NIH.GOV NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1612-3212 BN 978-3-319-19434-9; 978-3-319-19433-2 J9 ESSENT OPHTHALMOL PY 2016 BP 115 EP 116 D2 10.1007/978-3-319-19434-9 PG 2 WC Ophthalmology SC Ophthalmology GA BE8ET UT WOS:000376387400017 ER PT S AU Egwuagu, CE AF Egwuagu, Charles E. BE Chan, CC TI Animal Models of Ophthalmic Diseases Epilogue SO ANIMAL MODELS OF OPHTHALMIC DISEASES SE Essentials in Ophthalmology LA English DT Editorial Material; Book Chapter C1 [Egwuagu, Charles E.] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Egwuagu, CE (reprint author), NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM EgwuaguC@NEI.NIH.GOV NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1612-3212 BN 978-3-319-19434-9; 978-3-319-19433-2 J9 ESSENT OPHTHALMOL PY 2016 BP 141 EP 142 DI 10.1007/978-3-319-19434-9_10 D2 10.1007/978-3-319-19434-9 PG 2 WC Ophthalmology SC Ophthalmology GA BE8ET UT WOS:000376387400023 ER PT J AU Dogan, BA Arduc, A Tuna, MM Berker, D Demirci, N Demirtas, S Cicekcioglu, H Guler, S AF Dogan, Bercem Aycicek Arduc, Ayse Tuna, Mazhar Muslum Berker, Dilek Demirci, Nilgun Demirtas, Semra Cicekcioglu, Hulya Guler, Serdar TI Autoimmune Fibrotic Adverse Reactions in One-Year Treatment with Cabergoline for Women with Prolactinoma SO ENDOCRINE METABOLIC & IMMUNE DISORDERS-DRUG TARGETS LA English DT Article DE Autoimmune adverse fibrotic reactions; Cabergoline treatment; prolactinoma ID DOPAMINE AGONIST THERAPY; VALVULAR HEART-DISEASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CARDIAC-VALVE REGURGITATION; PARKINSONS-DISEASE; TRICUSPID REGURGITATION; RHEUMATOID-ARTHRITIS; INCREASED PREVALENCE; 5-HT2B RECEPTORS; PERGOLIDE AB Aim: Cabergoline is related to an elevated risk of fibrotic adverse reactions including cardiac valvular and pleuropulmonary fibrosis. We investigated pulmonary and cardiac valve fibrosis and immunological markers before and after 3 and 12 months of treatment with cabergoline in women with prolactinoma. Material-Methods: The study included thirty-two women with newly diagnosed prolactinoma and 28 healthy women. CAB cumulative dose was 7.8 +/- 5.5 mg after 3-month therapy, and 31 +/- 22 mg after 12-month follow-up. The risk of autoimmune adverse fibrotic reactions related to CAB treatment including cardiac valvulopathy and pulmonary fibrosis were assessed by a transthoracic echocardiography and pulmonary function tests, respectively. Immunological markers including Antistreptolysin O, Rheumatoid factor, Immunglobuline E, Antinuchlear antibody were also evaluated. Results: Before the start of CAB therapy, the total prevalence of trace grade of mitral, aortic, pulmonic, and tricuspid valve regurgitations were found as 34%, 3%, 6.3%, and 39 % respectively in women with prolactinoma. After improving of prolactin levels with CAB treatment, no change was found in the prevalence of the all valve regurgitations. There was no deterioration in pulmonary function tests. Rheumatoid factor was found higher in newly diagnosed women with prolactinoma than in healthy women (p=0.01), and this was improved by CAB therapy (p=0.005). Conclusion: The prospective study indicated that sufficient cabergoline doses for a period of one year treatment of prolactinoma were not found to be related to fibrotic adverse reactions including cardiac valvular and pulmonary fibrosis or increased levels of immunological marker, apart from rheumatoid factor. For the first time Rf was found higher in newly diagnosed women with prolactinoma and was improved after cabergoline therapy. C1 [Dogan, Bercem Aycicek] Darica Farabi State Hosp, Endocrinol & Metab Dis, Kocaeli, Turkey. [Arduc, Ayse] NIDDK, Endocrine & Obes Branch, NIH, Bethesda, MD 20892 USA. [Tuna, Mazhar Muslum] Dicle Univ, Endocrinol & Metab Dis, Diyarbakir, Turkey. [Berker, Dilek; Guler, Serdar] Ankara Numune Training & Res Hosp, Endocrinol & Metab Dis, Ankara, Turkey. [Demirci, Nilgun] Ankara Ataturk Chest Dis & Chest Surg Training &, Ankara, Turkey. [Demirtas, Semra] Ankara Onkol Training & Res Hosp, Nuchlear Med, Ankara, Turkey. [Cicekcioglu, Hulya] Ankara Numune Training & Res Hosp, Dept Cardiol, Ankara, Turkey. [Guler, Serdar] Hitit Univ, Endocrinol & Metab Dis, Corum, Turkey. RP Dogan, BA (reprint author), Darica Farabi State Hosp, Dept Endocrinol & Metab, Darica, Kocaeli, Turkey. EM bercemay@gmail.com NR 51 TC 0 Z9 0 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5303 EI 2212-3873 J9 ENDOCR METAB IMMUNE JI Endocr. Metab. Immune Disord.-Drug Targets PY 2016 VL 16 IS 1 BP 47 EP 55 DI 10.2174/1871530316666160229120142 PG 9 WC Endocrinology & Metabolism; Immunology; Pharmacology & Pharmacy SC Endocrinology & Metabolism; Immunology; Pharmacology & Pharmacy GA DO3VG UT WOS:000377709800009 PM 26924497 ER PT J AU Wang, TY Lee, SY Chung, YL Chen, SL Li, CL Chang, YH Wang, LJ Chen, PS Chen, SH Chu, CH Huang, SY Tzeng, NS Hsieh, TH Lee, IH Chen, KC Yang, YK Hong, JS Lu, RB AF Wang, Tzu-Yun Lee, Sheng-Yu Chung, Yi-Lun Chen, Shiou-Lan Li, Chia-Ling Chang, Yun-Hsuan Wang, Liang-Jen Chen, Po See Chen, Shih-Heng Chu, Chun-Hsien Huang, San-Yuan Tzeng, Nian-Sheng Hsieh, Tsai-Hsin Lee, I. Hui Chen, Kao Chin Yang, Yen Kuang Hong, Jau-Shyong Lu, Ru-Band TI TPH1 and 5-HTTLPR Genes Specifically Interact in Opiate Dependence but Not in Alcohol Dependence SO EUROPEAN ADDICTION RESEARCH LA English DT Article DE TPH1; 5-HTT-linked promoter region; Gene-to-gene interaction; Alcohol dependence; Opiate dependence ID SEROTONIN TRANSPORTER GENE; NATIONAL EPIDEMIOLOGIC SURVEY; TRYPTOPHAN-HYDROXYLASE GENE; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; DSM-IV; JAPANESE POPULATION; HEROIN DEPENDENCE; USE DISORDERS; ANTISOCIAL PERSONALITY; DIAGNOSTIC INTERVIEW AB Background: Different drug dependencies may have unique genetic vulnerabilities. Changes in serotonin availability and function have been linked to addiction. We investigated whether 2 serotonergic polymorphisms, TPH1 A218C (rs1800532) and 5-HTT-linked promoter region (5-HTTLPR) (rs25531), are differently associated with alcohol or opiate dependence. Methods: Alcohol-dependent patients (n = 292), opiate-dependent patients (n = 309), and healthy controls (n = 301) were recruited from the Han Chinese population in Taiwan. Genotypes of TPH1 A218C and 5-HTTLPR polymorphisms were analyzed using a polymerase chain reaction with restriction fragment length polymorphism. Results: The genotype frequencies of the TPH1 A218C polymorphisms were not significantly different in the 3 groups. The genotype frequencies of the 5-HTTLPR S+ (S/S, S/L-G, L-G/L-G) polymorphisms were significantly higher in opiate-dependent patients (X-2 = 8.77, p = 0.01), but not after controlling for the covariates of age, gender, and interaction effect in logistic regression analysis. Moreover, there was a significant inter-action between the TPH1 A218C A/C and 5-HTTLPR S+ gene polymorphisms in opiate-dependent (OR 2.72, p = 0.01), but not in alcohol-dependent patients. Conclusions: Our data suggested that there may be a differential genetic vulnerability in serotonergic genes for alcohol and opiate addiction. However, replications of our findings are still needed. (C) 2016 S. Karger AG, Basel C1 [Wang, Tzu-Yun; Lee, Sheng-Yu; Chung, Yi-Lun; Chen, Shiou-Lan; Li, Chia-Ling; Chang, Yun-Hsuan; Chen, Po See; Hsieh, Tsai-Hsin; Lee, I. Hui; Chen, Kao Chin; Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ Hosp, Dept Psychiat, Kaohsiung, Taiwan. [Yang, Yen Kuang; Lu, Ru-Band] Kaohsiung Vet Gen Hosp, Inst Behav Med, Kaohsiung, Taiwan. [Chang, Yun-Hsuan; Lu, Ru-Band] Kaohsiung Vet Gen Hosp, Inst Allied Hlth Sci, Kaohsiung, Taiwan. [Chu, Chun-Hsien] Kaohsiung Vet Gen Hosp, Inst Mol Med, Kaohsiung, Taiwan. [Lee, Sheng-Yu] Kaohsiung Vet Gen Hosp, Dept Psychiat, Kaohsiung, Taiwan. [Chen, Po See; Lee, I. Hui; Chen, Kao Chin; Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Addict Res Ctr, Tainan 701, Taiwan. [Chung, Yi-Lun] Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci, Tainan 70101, Taiwan. [Chen, Shiou-Lan] Kaohsiung Med Univ, Lipid Sci & Aging Res Ctr, Coll Med, Grad Inst Med, Kaohsiung, Taiwan. [Wang, Liang-Jen] Kaohsiung Chang Gung Mem Hosp Univ, Dept Child & Adolescent Psychiat, Kaohsiung, Taiwan. [Wang, Liang-Jen] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan. [Yang, Yen Kuang] Natl Cheng Kung Univ Hosp, Dept Psychiat, Dou Liou Branch, Tainan, Yunlin, Taiwan. [Lu, Ru-Band] Natl Hlth Res Inst, Ctr Neuropsychiatr Res, Miaoli, Taiwan. [Chang, Yun-Hsuan] Asia Univ, Dept Psychol, Taichung, Taiwan. [Huang, San-Yuan; Tzeng, Nian-Sheng] Triserv Gen Hosp, Sch Med, Dept Psychiat, Taipei, Taiwan. [Tzeng, Nian-Sheng] Natl Def Med Ctr, Student Counseling Ctr, Taipei, Taiwan. [Hong, Jau-Shyong] NIEHS, Neurobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RP Lu, RB (reprint author), Natl Cheng Kung Univ, Coll Med & Hosp, Inst Allied Hlth Sci, Inst Behav Med,Dept Psychiat, 138 Sheng Li Rd, Tainan 70428, Taiwan. EM rblu@mail.ncku.edu.tw FU Ministry of Health [DOH98-TD-I-111-DD004]; National Cheng Kung University Project of Promoting Academic Excellence; Developing World Class Research Centers, Taiwan, Republic of China FX This study was supported in part by the Ministry of Health Grant DOH98-TD-I-111-DD004 (R.-B.L.); as well as by a grant from the National Cheng Kung University Project of Promoting Academic Excellence and Developing World Class Research Centers, Taiwan, Republic of China (R.-B.L.). NR 58 TC 1 Z9 1 U1 6 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1022-6877 EI 1421-9891 J9 EUR ADDICT RES JI Eur. Addict. Res. PY 2016 VL 22 IS 4 BP 201 EP 209 DI 10.1159/000444676 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA DO7VU UT WOS:000377991900004 PM 27045756 ER PT J AU Strauss, J Madan, RA Gulley, JL AF Strauss, Julius Madan, Ravi A. Gulley, James L. TI Considerations for the combination of anticancer vaccines and immune checkpoint inhibitors SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE Immune checkpoint inhibitors; therapeutic cancer vaccines; immunogenic intensification ID RESISTANT PROSTATE-CANCER; DOSE-ESCALATION TRIAL; RENAL-CELL CARCINOMA; PANCREATIC ADENOCARCINOMA; UNTREATED MELANOMA; PD-L1 EXPRESSION; LUNG-CANCER; PHASE-I; IPILIMUMAB; NIVOLUMAB AB Introduction: Over the past few years, trials evaluating immunotherapies, particularly immune checkpoint inhibitors, have revolutionized the standard model of cancer treatment, demonstrating significant antitumor responses and improved clinical outcomes across a wide array of tumors types. Yet, despite these compelling data, a major limitation has been that only a fraction of patients mount a response to single-agent immune checkpoint inhibition. However, a growing amount of preclinical and clinical data suggests that combining immune checkpoint inhibition, either with other immune checkpoint inhibitors or with therapeutic cancer vaccines, has the potential to improve the proportion of patients seeing long-term durable responses with these therapies.Areas Covered: We have reviewed the reported data on immune checkpoint inhibition as monotherapy and as combination therapy with other immune checkpoint inhibitors or therapeutic cancer vaccines. Data is reviewed on agents with FDA approval or breakthrough designation as of the writing of this manuscript.Expert Opinion: Particular focus is given to the combination of immune checkpoint inhibitors and therapeutic cancer vaccines which has the potential to increase efficacy compared to single agent immune checkpoint inhibition with minimal added toxicity. C1 [Strauss, Julius; Madan, Ravi A.; Gulley, James L.] Natl Canc Inst, Genitourinary Malignancies Branch, Ctr Canc Res, Bethesda, MD USA. [Strauss, Julius; Madan, Ravi A.; Gulley, James L.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 10 Room 12N-226, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), CONTACT James L Gulley, Bethesda, MD USA.; Gulley, JL (reprint author), NCI, NIH, 9000 Rockville Pike,Bldg 10 Room 12N-226, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 43 TC 3 Z9 3 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1471-2598 EI 1744-7682 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PY 2016 VL 16 IS 7 BP 895 EP 901 DI 10.1517/14712598.2016.1170805 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA DO6ZP UT WOS:000377932300006 PM 27010190 ER PT J AU Cheng, JY Ning, H Arora, BC Ying, ZG Miller, RW AF Cheng, Jason Y. Ning, Holly Arora, Barbara C. Ying Zhuge Miller, Robert W. TI Output factor comparison of Monte Carlo and measurement for Varian TrueBeam 6 MV and 10 MV flattening filter-free stereotactic radiosurgery system SO JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS LA English DT Article DE Monte Carlo; output factors; stereotactic radiosurgery; small field dosimetry ID SMALL-FIELD DOSIMETRY; DIODE DETECTORS; PHOTON; FORMALISM; BEAMS; MODEL AB The dose measurements of the small field sizes, such as conical collimators used in stereotactic radiosurgery (SRS), are a significant challenge due to many factors including source occlusion, detector size limitation, and lack of lateral electronic equilibrium. One useful tool in dealing with the small field effect is Monte Carlo (MC) simulation. In this study, we report a comparison of Monte Carlo simulations and measurements of output factors for the Varian SRS system with conical collimators for energies of 6 MV flattening filter-free (6 MV) and 10 MV flattening filter-free (10 MV) on the TrueBeam accelerator. Monte Carlo simulations of Varian's SRS system for 6 MV and 10 MV photon energies with cones sizes of 17.5 mm, 15.0 mm, 12.5 mm, 10.0 mm, 7.5 mm, 5.0 mm, and 4.0 mm were performed using EGSnrc (release V4 2.4.0) codes. Varian's version-2 phase-space files for 6 MV and 10 MV of TrueBeam accelerator were utilized in the Monte Carlo simulations. Two small diode detectors Edge (Sun Nuclear) and Small Field Detector (SFD) (IBA Dosimetry) were applied to measure the output factors. Significant errors may result if detector correction factors are not applied to small field dosimetric measurements. Although it lacked the machine-specific k(Qclin,Qmsr)(fclin,fmsr) correction factors for diode detectors in this study, correction factors were applied utilizing published studies conducted under similar conditions. For cone diameters greater than or equal to 12.5 mm, the differences between output factors for the Edge detector, SFD detector, and MC simulations are within 3.0% for both energies. For cone diameters below 12.5 mm, output factors differences exhibit greater variations. C1 [Cheng, Jason Y.; Ning, Holly; Arora, Barbara C.; Ying Zhuge; Miller, Robert W.] NCI, Radiat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10 CRC,Room B2-3663A, Bethesda, MD 20892 USA. RP Cheng, JY (reprint author), NCI, Radiat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10 CRC,Room B2-3663A, Bethesda, MD 20892 USA. EM Jason.Cheng@nih.gov FU Intramural Research Program of the National Cancer Institute, NIH FX The authors would like to thank Varian Medical Systems for providing detailed information of the Stereotactic Radiosurgery System and TrueBeam linear accelerator. This research was supported by the Intramural Research Program of the National Cancer Institute, NIH. NR 26 TC 0 Z9 0 U1 2 U2 3 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 1526-9914 J9 J APPL CLIN MED PHYS JI J. Appl. Clin. Med. Phys PY 2016 VL 17 IS 3 BP 100 EP 110 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DO3JO UT WOS:000377678100010 PM 28297351 ER PT J AU White, SF Briggs-Gowan, MJ Voss, JL Petitclerc, A McCarthy, K Blair, RJR Wakschlag, LS AF White, Stuart F. Briggs-Gowan, Margaret J. Voss, Joel L. Petitclerc, Amelie McCarthy, Kimberly Blair, R. James R. Wakschlag, Lauren S. TI Can the fear recognition deficits associated with callous-unemotional traits be identified in early childhood? SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE Disruptive behavior; emotion recognition; developmental; callousunemotional traits ID PRESCHOOL DISRUPTIVE BEHAVIOR; CONDUCT PROBLEMS; ANTISOCIAL-BEHAVIOR; DEVELOPMENTAL PSYCHOPATHOLOGY; AGGRESSIVE-BEHAVIOR; FACIAL EXPRESSIONS; AMYGDALA RESPONSE; EXPECTED VALUE; CHILDREN; EMOTION AB Introduction: Callous-unemotional (CU) traits in the presence of conduct problems are associated with increased risk of severe antisocial behavior. Developmentally sensitive methods of assessing CU traits have recently been generated, but their construct validity in relation to neurocognitive underpinnings of CU has not been demonstrated. The current study sought to investigate whether the fear-specific emotion recognition deficits associated with CU traits in older individuals are developmentally expressed in young children as low concern for others and punishment insensitivity. Method: A subsample of 337 preschoolers (mean age 4.8 years, SD = 0.8) who completed neurocognitive tasks was taken from a larger project of preschool psychopathology. Children completed an emotional recognition task in which they were asked to identify the emotional face from the neutral faces in an array. CU traits were assessed using the Low Concern (LC) and Punishment Insensitivity (PI) subscales of the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB), which were specifically designed to differentiate the normative misbehavior of early childhood from atypical patterns. Results: High LC, but not PI, scores were associated with a fear-specific deficit in emotion recognition. Girls were more accurate than boys in identifying emotional expressions but no significant interaction between LC or PI and sex was observed. Conclusions: Fear recognition deficits associated with CU traits in older individuals were observed in preschoolers with developmentally defined patterns of low concern for others. Confirming that the link between CU-related impairments in empathy and distinct neurocognitive deficits is present in very young children suggests that developmentally specified measurement can detect the substrates of these severe behavioral patterns beginning much earlier than prior work. Exploring the development of CU traits and disruptive behavior disorders at very early ages may provide insights critical to early intervention and prevention of severe antisocial behavior. C1 [White, Stuart F.; Blair, R. James R.] NIMH, Sect Affect Cognit Neurosci, Bethesda, MD 20892 USA. [Briggs-Gowan, Margaret J.; McCarthy, Kimberly] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Voss, Joel L.; Petitclerc, Amelie; Wakschlag, Lauren S.] Northwestern Univ, Dept Med Social Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Wakschlag, Lauren S.] Northwestern Univ, Inst Policy Res, Chicago, IL 60611 USA. RP White, SF (reprint author), NIMH, Sect Affect Cognit Neurosci, Bethesda, MD 20892 USA. EM stuart.white@nih.gov FU Intramural Research Program of the National Institute of Mental Health, National Institutes of Health [1-ZIA-MH002860]; National Institute of Mental Health (NIMH) [R01MH082830, 2U01MH082830, U01MH090301]; Walden & Jean Young Shaw Foundation FX Stuart F. White and R. James R. Blair were supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health [grant number 1-ZIA-MH002860], R. James R. Blair principal investigator. Lauren S. Wakschlag, Margaret J. Briggs-Gowan, Joel L. Voss, and Kimberly McCarthy were supported by National Institute of Mental Health (NIMH) grants [grant number R01MH082830], [grant number 2U01MH082830], and [grant number U01MH090301]. Lauren S. Wakschlag was also supported by the Walden & Jean Young Shaw Foundation. NR 53 TC 0 Z9 0 U1 4 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1380-3395 EI 1744-411X J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PY 2016 VL 38 IS 6 BP 672 EP 684 DI 10.1080/13803395.2016.1149154 PG 13 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA DO5IZ UT WOS:000377818100006 PM 27167866 ER PT J AU Tom, WL Playford, MP Admani, S Natarajan, B Joshi, AA Eichenfield, LF Mehta, NN AF Tom, Wynnis L. Playford, Martin P. Admani, Shehla Natarajan, Balaji Joshi, Aditya A. Eichenfield, Lawrence F. Mehta, Nehal N. TI Characterization of Lipoprotein Composition and Function in Pediatric Psoriasis Reveals a More Atherogenic Profile SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID CHOLESTEROL EFFLUX CAPACITY; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; METABOLIC SYNDROME; PARTICLE NUMBER; RISK; INFLAMMATION; CHILDREN; ASSOCIATION; INDEXES AB Psoriasis is associated with increased cardiovascular disease in adults, but the risk profile of children with psoriasis remains to be fully characterized. We measured lipoprotein composition and function in 44 patients with pediatric psoriasis and 44 age-and sex-matched healthy controls, using nuclear magnetic resonance spectroscopy and a validated ex vivo assay of high-density lipoprotein cholesterol efflux capacity. The mean age of the patients was 13 years and the population was ethnically diverse. Children with psoriasis had higher waist-to-hip ratios (0.85 vs. 0.80; P < 0.002) and insulin resistance measures (log-transformed homeostasis model assessment of insulin resistance 0.65 vs. 0.41; P = 0.07). Despite comparable traditional lipid values, having psoriasis was associated with higher apolipoprotein B concentrations (72.4 vs. 64.6; P = 0.02), decreased large high-density lipoprotein particles (5.3 vs. 6.7; P < 0.01), and reduced cholesterol efflux capacity after adjusting for age, sex, fasting glucose, homeostasis model assessment of insulin resistance, systolic blood pressure, body mass index, apolipoprotein A-1, and high-density lipoprotein cholesterol concentration (beta -0.22; P = 0.02). Patients with pediatric psoriasis have a more atherogenic cardiometabolic risk profile, with evidence of insulin resistance and lipoprotein dysfunction by particle size, number, and functional assessment. These findings may provide a basis for the observed link later in life between psoriasis and cardiovascular disease, and support the need to screen and educate young patients to minimize later complications. C1 [Tom, Wynnis L.; Admani, Shehla; Eichenfield, Lawrence F.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Tom, Wynnis L.; Admani, Shehla; Eichenfield, Lawrence F.] Univ Calif San Diego, Dept Med Dermatol, San Diego, CA 92103 USA. [Tom, Wynnis L.; Admani, Shehla; Eichenfield, Lawrence F.] Rady Childrens Hosp, 8010 Frost St,Suite 602, San Diego, CA 92123 USA. [Playford, Martin P.; Natarajan, Balaji; Joshi, Aditya A.; Mehta, Nehal N.] NIH, Cardiol Branch, Bldg 10, Bethesda, MD 20892 USA. RP Tom, WL (reprint author), Rady Childrens Hosp, 8010 Frost St,Suite 602, San Diego, CA 92123 USA.; Tom, WL (reprint author), Univ Calif San Diego, Pediat & Adolescent Dermatol, 8010 Frost St,Suite 602, San Diego, CA 92123 USA. EM wtom@rchsd.org FU National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health [K23AR060274]; [NHLBIHL006193-01] FX WLT is supported by a Career Development Award (K23AR060274) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health. NNM is a Lasker Clinical Research Scholar in the Section of Inflammation and Cardiometabolic Diseases of the National Heart, Lung, and Blood Institute (supported by grant to the Intramural Research Program NHLBIHL006193-01). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 34 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2016 VL 136 IS 1 BP 67 EP 73 DI 10.1038/JID.2015.385 PG 7 WC Dermatology SC Dermatology GA DO7HJ UT WOS:000377952900016 PM 26763425 ER PT J AU Dunlap, LJ Han, B Dowd, WN Cowell, AJ Forman-Hoffman, VL Davies, MC Colpe, LJ AF Dunlap, Laura J. Han, Beth Dowd, William N. Cowell, Alexander J. Forman-Hoffman, Valerie L. Davies, M. Christine Colpe, Lisa J. TI Behavioral Health Outcomes Among Adults: Associations With Individual and Community-Level Economic Conditions SO PSYCHIATRIC SERVICES LA English DT Article ID NONSPECIFIC PSYCHOLOGICAL DISTRESS; MENTAL-HEALTH; ALCOHOL-CONSUMPTION; SUBSTANCE USE; SERVICE USE; UNEMPLOYMENT; POPULATION; EPIDEMIOLOGY; PREVALENCE; DISORDERS AB Objective: This study examined the relationship between state and local economic conditions and serious psychological distress, substance use disorders, and mental health service utilization among adults in the United States. Methods: Using data from 21,100 adults who responded to the 2008-2010 National Survey on Drug Use and Health, a nationally representative survey of the U.S. civilian non-institutionalized population living in households, the study used multivariate methods to examine associations between selected macroeconomic conditions and behavioral health outcomes. Results: Living in states in the top three quartiles for serious mortgage delinquency rate and in counties in the top three quartiles for unemployment rate was associated with a lower likelihood of using mental health services among individuals experiencing serious psychological distress (adjusted relative risk [ARR] = .54, .52, and .73, and ARR = .58, .62, and .71, respectively, versus quartile 1). Individual level characteristics were the primary predictors associated with higher odds of having substance use disorders or experiencing serious psychological distress, but macroeconomic variables were not statistically significant predictors of these outcomes. Conclusions: Both individual-level socioeconomic characteristics and population-level macroeconomic conditions were associated with behavioral health outcomes. Prevalence of serious psychological distress and substance use disorders and use of mental health services varied by economic measure. The findings suggest that access to and availability of mental health services for individuals experiencing serious psychological distress may be more challenging for those who do not have health insurance or who reside in regions with higher rates of mortgage foreclosures or higher rates of unemployment. C1 [Dunlap, Laura J.; Dowd, William N.; Cowell, Alexander J.; Forman-Hoffman, Valerie L.; Davies, M. Christine] RTI Int, Res Triangle Pk, NC 27709 USA. [Han, Beth] Subst Abuse & Mental Hlth Serv Adm, Ctr Behav Hlth Qual & Stat, Rockville, MD USA. [Davies, M. Christine] Quintiles Inc, Durham, NC USA. [Colpe, Lisa J.] NIMH, Off Clin & Populat Epidemiol Res, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Dunlap, LJ (reprint author), RTI Int, Res Triangle Pk, NC 27709 USA. EM ljd@rti.org FU Substance Abuse and Mental Health Services Administration - National Institute of Mental Health [HHSS283200800004C] FX This study was funded under Substance Abuse and Mental Health Services Administration contract no. HHSS283200800004C, which was supported by funding from the National Institute of Mental Health. The authors are thankful for the thoughtful comments by Albert Woodward, Ph.D., and Mir Ali, Ph.D. The views expressed do not necessarily represent the views of the National Institutes of Health, the Substance Abuse and Mental Health Services Administration, and the U.S. Department of Health and Human Services. NR 43 TC 1 Z9 1 U1 2 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JAN PY 2016 VL 67 IS 1 BP 71 EP 77 DI 10.1176/appi.ps.201400016 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DO4SX UT WOS:000377775000013 PM 26325454 ER PT J AU Jing, H Weidensteiner, C Reichardt, W Gaedicke, S Zhu, XK Grosu, AL Kobayashi, H Niedermann, G AF Jing, Hua Weidensteiner, Claudia Reichardt, Wilfried Gaedicke, Simone Zhu, Xuekai Grosu, Anca-Ligia Kobayashi, Hisataka Niedermann, Gabriele TI Imaging and Selective Elimination of Glioblastoma Stem Cells with Theranostic Near-Infrared-Labeled CD133-Specific Antibodies SO THERANOSTICS LA English DT Article DE near-infrared photoimmunotherapy; cancer stem cells; CD133; glioblastoma ID FLUORESCENCE-GUIDED SURGERY; TUMOR-INITIATING CELLS; PHOTODYNAMIC THERAPY; ENHANCED PERMEABILITY; OVARIAN-CANCER; BREAST-CANCER; PHOTOIMMUNOTHERAPY; GLIOMA; DIFFERENTIATION; RESISTANCE AB Near-infrared photoimmunotherapy (NIR-PIT), which employs monoclonal antibody (mAb)-phototoxic phthalocyanine dye IR700 conjugates, permits the specific, image-guided and spatiotemporally controlled elimination of tumor cells. Here, we report the highly efficient NIR-PIT of human tumor xenografts initiated from patient-derived cancer stem cells (CSCs). Using glioblastoma stem cells (GBM-SCs) expressing the prototypic CSC marker AC133/CD133, we also demonstrate here for the first time that NIR-PIT is highly effective against brain tumors. The intravenously injected theranostic AC133 mAb conjugate enabled the non-invasive detection of orthotopic gliomas by NIR fluorescence imaging, and reached AC133+ GBM-SCs at the invasive tumor front. AC133-targeted NIR-PIT induced the rapid cell death of AC133+ GBM-SCs and thereby strong shrinkage of both subcutaneous and invasively growing brain tumors. A single round of NIR-PIT extended the overall survival of mice with established orthotopic gliomas by more than a factor of two, even though the harmless NIR light was applied through the intact skull. Humanised versions of this theranostic agent may facilitate intraoperative imaging and histopathological evaluation of tumor borders and enable the highly specific and efficient eradication of CSCs. C1 [Jing, Hua; Gaedicke, Simone; Zhu, Xuekai; Grosu, Anca-Ligia; Niedermann, Gabriele] Univ Hosp Freiburg, Dept Radiat Oncol, D-79106 Freiburg, Germany. [Weidensteiner, Claudia; Reichardt, Wilfried] Univ Hosp Freiburg, Radiol Med Phys, D-79106 Freiburg, Germany. [Jing, Hua; Zhu, Xuekai; Grosu, Anca-Ligia; Niedermann, Gabriele] German Canc Consortium DKTK, Freiburg, Germany. [Jing, Hua; Zhu, Xuekai; Grosu, Anca-Ligia; Niedermann, Gabriele] German Canc Res Ctr, D-69121 Heidelberg, Germany. [Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Niedermann, G (reprint author), Univ Hosp Freiburg, Dept Radiat Oncol, D-79106 Freiburg, Germany.; Niedermann, G (reprint author), German Canc Consortium DKTK, Freiburg, Germany.; Niedermann, G (reprint author), German Canc Res Ctr, D-69121 Heidelberg, Germany. EM gabriele.niedermann@uniklinik-freiburg.de NR 53 TC 1 Z9 1 U1 7 U2 14 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2016 VL 6 IS 6 BP 862 EP 874 DI 10.7150/thno.12890 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DO5BO UT WOS:000377798800009 PM 27162556 ER PT S AU Dr Nussenblatt AF Dr Nussenblatt BE Chan, CC TI Animal Models of Autoimmune Uveitis Commentary SO ANIMAL MODELS OF OPHTHALMIC DISEASES SE Essentials in Ophthalmology LA English DT Editorial Material; Book Chapter C1 [Dr Nussenblatt] NEI, Immunol Lab, UNITE Lab, Ctr Human Immunol,NIH, Bldg 10, Bethesda, MD 20892 USA. RP Dr Nussenblatt (reprint author), NEI, Immunol Lab, UNITE Lab, Ctr Human Immunol,NIH, Bldg 10, Bethesda, MD 20892 USA. EM nussenblattr@nei.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1612-3212 BN 978-3-319-19434-9; 978-3-319-19433-2 J9 ESSENT OPHTHALMOL PY 2016 BP 99 EP 100 D2 10.1007/978-3-319-19434-9 PG 2 WC Ophthalmology SC Ophthalmology GA BE8ET UT WOS:000376387400015 ER PT S AU Jager, MJ Cao, JF Yang, H Decaudin, D Kalirai, H van der Ent, W de Waard, NE Cassoux, N Aronow, ME Nair, RM Coupland, SE AF Jager, Martine J. Cao, Jinfeng Yang, Hua Decaudin, Didier Kalirai, Helen van der Ent, Wietske de Waard, Nadine E. Cassoux, Nathalie Aronow, Mary E. Nair, Rohini M. Coupland, Sarah E. BE Chan, CC TI Animal Models of Ocular Tumors SO ANIMAL MODELS OF OPHTHALMIC DISEASES SE Essentials in Ophthalmology LA English DT Article; Book Chapter ID HUMAN UVEAL MELANOMA; NERVOUS-SYSTEM LYMPHOMA; DEPENDENT PROBE AMPLIFICATION; PRIMARY INTRAOCULAR LYMPHOMA; HAMSTER GREENE MELANOMA; COPY NUMBER CHANGES; CELL-LINES; CHOROIDAL MELANOMA; CONJUNCTIVAL MELANOMA; MURINE MODEL C1 [Jager, Martine J.; Cao, Jinfeng; de Waard, Nadine E.] Leiden Univ, Med Ctr, Dept Ophthalmol, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands. [Yang, Hua] Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA. [Decaudin, Didier] Inst Curie, Lab Preclin Invest, Translat Res Dept, Paris, France. [Kalirai, Helen; Coupland, Sarah E.] Univ Liverpool, Pathol, Dept Mol & Clin Canc Med, Inst Translat Res, Liverpool L69 3BX, Merseyside, England. [van der Ent, Wietske] Leiden Univ, Dept Pathol, Inst Biol, Med Ctr, Leiden, Netherlands. [Cassoux, Nathalie] Inst Curie, Dept Oncol Chirurg, Inst & Lab Preclin Invest, Dept Translat Res, Paris, France. [Aronow, Mary E.] NEI, Clin Branch, NIH, Bethesda, MD 20892 USA. [Nair, Rohini M.] Univ Hyderabad, Sch Med Sci, Hyderabad 500134, Andhra Pradesh, India. RP Jager, MJ (reprint author), Leiden Univ, Med Ctr, Dept Ophthalmol, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands. EM m.j.jager@lumc.nl NR 112 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1612-3212 BN 978-3-319-19434-9; 978-3-319-19433-2 J9 ESSENT OPHTHALMOL PY 2016 BP 127 EP 140 DI 10.1007/978-3-319-19434-9_9 D2 10.1007/978-3-319-19434-9 PG 14 WC Ophthalmology SC Ophthalmology GA BE8ET UT WOS:000376387400021 ER PT J AU Heiss, DR Zehnder, DW Jett, DA Platoff, GE Yeung, DT Brewer, BN AF Heiss, Derik R. Zehnder, Donald W., II Jett, David A. Platoff, Gennady E., Jr. Yeung, David T. Brewer, Bobby N. TI Synthesis and Storage Stability of Diisopropylfluorophosphate SO JOURNAL OF CHEMISTRY LA English DT Article ID TOXICITY; REAGENT; RAT AB Diisopropylfluorophosphate (DFP) is a potent acetylcholinesterase inhibitor commonly used in toxicological studies as an organophosphorus nerve agent surrogate. However, LD50, values for DFP in the same species can differ widely even within the same laboratory, possibly due to the use of degraded DFP. The objectives here were to identify an efficient synthesis route for high purity DPP and assess the storage stability of both the in-house synthesized and commercial source of DFP at the manufacturer recommended storage temperature of 4 degrees C, as well as -10 degrees C and -80 degrees C. After 393 days, the commercial DFP stored at 4 degrees C experienced significant degradation, while only minor degradation was observed at -10 degrees C and none was observed at -80 degrees C. DFP prepared using the newly identified synthesis route was significantly more stable, exhibiting only minor degradation at CC and none at -10 degrees C or -80 degrees C. The major degradation product was the monoacid derivative diisopropylphosphate, formed via hydrolysis of DFP. It was also found that storing DFP in glass containers may accelerate the degradation process by generating water in situ as hydrolytically generated hydrofluoric acid attacks the silica in the glass. Based on the results here, it is recommended that DFP he stored at or below -10 degrees C, preferably in air-tight, nonglass containers. C1 [Heiss, Derik R.; Zehnder, Donald W., II; Brewer, Bobby N.] Battelle Mem Inst, 505 King Ave, Columbus, OH 43201 USA. [Jett, David A.; Yeung, David T.] NINDS, NIH, 6001 Execut Blvd, Rockville, MD 20852 USA. [Platoff, Gennady E., Jr.] NIAID, NIH, 5601 Fishers Lane, Rockville, MD 20892 USA. RP Brewer, BN (reprint author), Battelle Mem Inst, 505 King Ave, Columbus, OH 43201 USA. EM brewerb@battelle.org OI Brewer, Bobby/0000-0003-4384-3078 FU National Institutes of Health Office of the Director [Y1-OD-0387-01]; NIH, NIAID, NINDS; DoD Defense Technical Information Center (DTIC) via the Chemical, Biological, Radiological & Nuclear Defense Information Analysis Center (CBRNIAC) program [SP0700-00-D-3180, 0794, 689/CB-13-0689] FX Funding for this work was provided by the National Institutes of Health Office of the Director through an interagency agreement (Y1-OD-0387-01) between the National Institute of Allergy and Infectious Diseases (NIAID) and Department of Defense (DoD) and prepared under the auspices of the NIH, NIAID, NINDS, and the DoD Defense Technical Information Center (DTIC) via the Chemical, Biological, Radiological & Nuclear Defense Information Analysis Center (CBRNIAC) program, Contract no. SP0700-00-D-3180, Delivery Order no. 0794, CBRNIAC Task 689/CB-13-0689. NR 14 TC 0 Z9 0 U1 3 U2 5 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2090-9063 EI 2090-9071 J9 J CHEM-NY JI J. Chem. PY 2016 AR 3190891 DI 10.1155/2016/3190891 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA DO0AM UT WOS:000377441800001 ER PT J AU Lee, J Romero, R Kim, SM Chaemsaithong, P Yoon, BH AF Lee, JoonHo Romero, Roberto Kim, Sun Min Chaemsaithong, Piya Yoon, Bo Hyun TI A new antibiotic regimen treats and prevents intra-amniotic inflammation/infection in patients with preterm PROM SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Ceftriaxone; chorioamnionitis; clarithromycin; erythromycin; funisitis; metronidazole; neonatal morbidity; neonatal sepsis; pregnancy; prematurity; preterm birth; preterm labor; placental pathology ID PLACEBO-CONTROLLED TRIAL; BLOOD-CELL COUNT; FLUID MATRIX METALLOPROTEINASE-8; MATERNAL SERUM INTERLEUKIN-6; ADVERSE PREGNANCY OUTCOMES; RANDOMIZED CLINICAL-TRIAL; WHITE-MATTER LESIONS; BIRTH-WEIGHT INFANTS; C-REACTIVE PROTEIN; PREMATURE RUPTURE AB Objectives: To determine whether a new antibiotic regimen could reduce the frequency of intra-amniotic inflammation/infection in patients with preterm PROM. Study design: This retrospective cohort study was conducted to evaluate the effect of antibiotics on the frequency of intra-amniotic inflammation/infection based on the results of follow-up transabdominal amniocenteses from 89 patients diagnosed with preterm PROM who underwent serial amniocenteses. From 1993-2003, ampicillin and/or cephalosporins or a combination was used ("regimen 1''). A new regimen (ceftriaxone, clarithromycin and metronidazole) was used from 2003-2012 ("regimen 2''). Amniotic fluid was cultured and matrix metalloproteinase-8 (MMP-8) concentrations were measured. Results: (1) The rates of intra-amniotic inflammation and intra-amniotic inflammation/infection in patients who received regimen 2 decreased during treatment from 68.8% to 52.1% and from 75% to 54.2%, respectively. In contrast, in patients who received regimen 1, the frequency of intra-amniotic inflammation and infection/inflammation increased during treatment (31.7% to 55% and 34.1% to 58.5%, respectively); and (2) intra-amniotic inflammation/infection was eradicated in 33.3% of patients who received regimen 2, but in none who received regimen 1. Conclusion: The administration of ceftriaxone, clarithromycin and metronidazole was associated with a more successful eradication of intra-amniotic inflammation/infection and prevented secondary intra-amniotic inflammation/infection more frequently than an antibiotic regimen which included ampicillin and/or cephalosporins in patients with preterm PROM. C1 [Lee, JoonHo; Kim, Sun Min; Yoon, Bo Hyun] Seoul Natl Univ, Dept Obstet & Gynecol, Coll Med, Seoul 110744, South Korea. [Romero, Roberto; Chaemsaithong, Piya] NICHD, Perinatol Res Branch, Program Perinatal Res & Obstet,NIH,DHHS, Div Intramural Res,Eunice Kennedy Shriver Natl In, Bethesda, MD USA. [Romero, Roberto; Chaemsaithong, Piya] NICHD, Perinatol Res Branch, Program Perinatal Res & Obstet,NIH,DHHS, Div Intramural Res,Eunice Kennedy Shriver Natl In, Detroit, MI USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Kim, Sun Min] Seoul Natl Univ, Dept Obstet & Gynecol, Seoul Metropolitan Govt, Boramae Med Ctr, Seoul, South Korea. [Chaemsaithong, Piya] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Yoon, BH (reprint author), Seoul Natl Univ, Dept Obstet & Gynecol, Coll Med, Seoul 110744, South Korea.; Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R, Detroit, MI 48201 USA. EM romeror@mail.nih.gov; yoonbh@snu.ac.kror FU Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI12C0768]; Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS) FX The authors report no conflicts of interest. This research was supported by a grant of the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI12C0768). This research was also supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS). NR 179 TC 0 Z9 0 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2016 VL 29 IS 17 BP 2727 EP 2737 DI 10.3109/14767058.2015.1103729 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DN7LH UT WOS:000377256800001 PM 26441216 ER PT J AU Gharwan, H Lai, C Grant, C Dunleavy, K Steinberg, SM Shovlin, M Fojo, T Wilson, WH AF Gharwan, Helen Lai, Catherine Grant, Cliona Dunleavy, Kieron Steinberg, Seth M. Shovlin, Margaret Fojo, Tito Wilson, Wyndham H. TI Female fertility following dose-adjusted EPOCH-R chemotherapy in primary mediastinal B-cell lymphomas SO LEUKEMIA & LYMPHOMA LA English DT Article DE Aggressive B-cell lymphoma; DA-EPOCH-R; fertility following chemotherapy; fertility; primary mediastinal B-cell lymphoma ID ANTI-MULLERIAN HORMONE; PREMATURE OVARIAN FAILURE; FRANKFURT-MUNSTER GROUP; NON-HODGKIN-LYMPHOMA; GONADOTROPIN-SECRETION; PLUS RITUXIMAB; CANCER; WOMEN; CHOP; MENOPAUSE AB We assessed fertility/gonadal function in premenopausal women treated with dose-adjusted EPOCH-Rituximab for untreated primary mediastinal B-cell lymphoma (PMBL). Eligible patents were <= 50 years and premenopausal. Serial reproductive histories were obtained and hormonal assays were performed on serum samples before, at the end of treatment and 4-18 months later. Twenty-eight eligible women had a median age (range) of 31 (21-50) years and were followed a median of 7.3 years. Of 23 patients who completed a questionnaire, 19 (83%) were and four were not menstruating prior to chemotherapy. Amenorrhea developed in 12 patients during chemotherapy. At >1-year follow-up, 14/19 (74%) patients were menstruating, all <35 years old, and six (43%) of these patients delivered healthy children. Hormonal assays showed ovarian dysfunction during chemotherapy in all patients with varying recovery at 4-18 months after treatment. Fertility was preserved in most women with ovarian failure confined to patients >40 years old. C1 [Gharwan, Helen; Lai, Catherine; Grant, Cliona; Dunleavy, Kieron; Shovlin, Margaret; Wilson, Wyndham H.] NCI, Lymphoid Malignancy Branch, Ctr Canc Res, Bldg 10,Room 4N-115,9000 Rockville Pike, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Fojo, Tito] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), NCI, Lymphoid Malignancy Branch, Ctr Canc Res, Bldg 10,Room 4N-115,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov NR 30 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2016 VL 57 IS 7 BP 1616 EP 1624 DI 10.3109/10428194.2015.1118476 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA DN7OB UT WOS:000377265000020 PM 27183887 ER PT S AU Stoff, S Chue-Sang, J Holness, NA Gandjbakhche, A Chernomordik, V Ramella-Roman, J AF Stoff, Susan Chue-Sang, Joseph Holness, Nola A. Gandjbakhche, Amir Chernomordik, Viktor Ramella-Roman, Jessica BE Choi, B Kollias, N Zeng, H Kang, HW Wong, BJF Ilgner, JF Tearney, GJ Gregory, KW Marcu, L Skala, MC Campagnola, PJ Mandelis, A TI Cervical Collagen Imaging for Determining Preterm Labor Risks Using a Colposcope with Full Mueller Matrix Capability SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS XII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics XII CY FEB 13-14, 2016 CL San Francisco, CA SP SPIE DE Mueller Matrix; Preterm Birth; Collagen Disorganization; Polarization; Colposcope AB Preterm birth is a worldwide health issue, as the number one cause of infant mortality and neurological disorders. Although affecting nearly 10% of all births, an accurate, reliable diagnostic method for preterm birth has, yet, to be developed. The primary constituent of the cervix, collagen, provides the structural support and mechanical strength to maintain cervical closure, through specific organization, during fetal gestation. As pregnancy progresses, the disorganization of the cervical collagen occurs to allow eventual cervical pliability so the baby can be birthed through the cervical opening. This disorganization of collagen affects the mechanical properties of the cervix and, if the changes occur prematurely, may be a significant factor leading to preterm birth. The organization of collagen can be analyzed through the use of Mueller Matrix Polarimetric imaging of the characteristic birefringence of collagen. In this research, we have built a full Mueller Matrix Polarimetry attachment to a standard colposcope to enable imaging of human cervixes during standard prenatal exams at various stages of fetal gestation. Analysis of the polarimetric images provides information of quantity and organization of cervical collagen at specific gestational stages of pregnancy. This quantitative information may provide an indication of risk of preterm birth. C1 [Stoff, Susan; Chue-Sang, Joseph; Ramella-Roman, Jessica] Florida Int Univ, Dept Biomed Engn, Med Photon Lab, Miami, FL 33199 USA. [Holness, Nola A.; Ramella-Roman, Jessica] Florida Int Univ, Herbert Wertheim Coll Med, Miami, FL 33199 USA. [Gandjbakhche, Amir; Chernomordik, Viktor] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Ramella-Roman, J (reprint author), Florida Int Univ, Dept Biomed Engn, Med Photon Lab, Miami, FL 33199 USA.; Ramella-Roman, J (reprint author), Florida Int Univ, Herbert Wertheim Coll Med, Miami, FL 33199 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-924-5 J9 PROC SPIE PY 2016 VL 9689 AR 968947 DI 10.1117/12.2213387 PG 5 WC Microscopy; Optics SC Microscopy; Optics GA BE9FK UT WOS:000377396200112 ER PT J AU Knittel, LL Schuck, P Ackerson, CJ Sousa, AA AF Knittel, Luiza L. Schuck, Peter Ackerson, Christopher J. Sousa, Alioscka A. TI Zwitterionic glutathione monoethyl ester as a new capping ligand for ultrasmall gold nanoparticles SO RSC ADVANCES LA English DT Article ID RENAL CLEARANCE; DELIVERY; SURFACE; TUMORS; BIODISTRIBUTION; NANOCLUSTERS; SYSTEMS; SIZE AB The natural tripeptide glutathione has become a popular choice for passivating the surface of gold nanoparticles (NPs) intended for in vivo applications. Here we investigate a zwitterionic derivative of glutathione - glutathione monoethyl ester - as a new capping ligand for ultrasmall NPs. The new zwitterionic particles (AuGSH(zwt)) were colloidally stable in biological media and resistant against binding from serum proteins. AuGSH(zwt), but not glutathione-coated particles, could be successfully functionalized with strep-tag II for binding specifically to target streptactin in the presence of serum proteins. Taken together, these results place AuGSH(zwt) as a promising choice for attaining simultaneous in vivo renal clearance and targeted delivery via incorporation of functional peptides. C1 [Knittel, Luiza L.; Sousa, Alioscka A.] Univ Fed Sao Paulo, Dept Biochem, BR-04044 Sao Paulo, Brazil. [Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. [Ackerson, Christopher J.] Colorado State Univ, Dept Chem, Ft Collins, CO 80521 USA. RP Sousa, AA (reprint author), Univ Fed Sao Paulo, Dept Biochem, BR-04044 Sao Paulo, Brazil. EM alioscka.sousa@unifesp.br FU Sao Paulo Research Foundation (FAPESP) [2013/18481-5]; Brazilian National Council for Scientific and Technological Development (CNPq) [476784/2013-1] FX We would like to acknowledge Prof. M. L. V. Oliva for providing access to instrumentation, and Dr M. A. Aronova and Dr R. D. Leapman for images of gold nanoparticles. We acknowledge the Spectroscopy and Calorimetry facility at Brazilian Biosciences National Laboratory (LNBio/CNPEM) for their support with the analytical ultracentrifuge. This work was supported by the Sao Paulo Research Foundation (FAPESP: 2013/18481-5) and by the Brazilian National Council for Scientific and Technological Development (CNPq: 476784/2013-1). CJA acknowledges NSF CHE 1455099. NR 39 TC 0 Z9 0 U1 7 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2046-2069 J9 RSC ADV JI RSC Adv. PY 2016 VL 6 IS 52 BP 46350 EP 46355 DI 10.1039/c6ra07777c PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA DN7KP UT WOS:000377254800036 ER PT S AU DePamphilis, ML AF DePamphilis, Melvin L. BE Wassarman, PM TI Genome Duplication: The Heartbeat of Developing Organisms SO ESSAYS ON DEVELOPMENTAL BIOLOGY, PT A SE Current Topics in Developmental Biology LA English DT Review; Book Chapter ID DNA-REPLICATION ORIGINS; DEVELOPMENTAL GENE AMPLIFICATION; PREIMPLANTATION MOUSE EMBRYOS; XENOPUS EGG EXTRACTS; RE-REPLICATION; CELL-CYCLE; S-PHASE; DROSOPHILA-MELANOGASTER; MAMMALIAN DEVELOPMENT; RECOGNITION COMPLEX AB The mechanism that duplicates the nuclear genome during the trillions of cell divisions required to develop from zygote to adult is the same throughout the eukarya, but the mechanisms that determine where, when and how much nuclear genome duplication occur regulate development and differ among the eukarya. They allow organisms to change the rate of cell proliferation during development, to activate zygotic gene expression independently of DNA replication, and to restrict nuclear DNA replication to once per cell division. They allow specialized cells to exit their mitotic cell cycle and differentiate into polyploid cells, and in some cases, to amplify the number of copies of specific genes. It is genome duplication that drives evolution, by virtue of the errors that inevitably occur when the same process is repeated trillions of times. It is, unfortunately, the same errors that produce age-related genetic disorders such as cancer. C1 [DePamphilis, Melvin L.] NICHHD, NIH, Bethesda, MD 20892 USA. RP DePamphilis, ML (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM depamphm@mail.nih.gov FU Intramural NIH HHS [Z01 HD000506-12, Z01 HD000507-12, Z01 HD000507-13] NR 132 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 BN 978-0-12-802976-3; 978-0-12-802956-5 J9 CURR TOP DEV BIOL JI Curr. Top. Dev. Biol. PY 2016 VL 116 BP 201 EP + DI 10.1016/bs.ctdb.2015.10.002 PG 35 WC Developmental Biology SC Developmental Biology GA BE8RP UT WOS:000376939100013 PM 26970621 ER PT J AU El Haj, M Kapogiannis, D Antoine, P AF El Haj, Mohamad Kapogiannis, Dimitrios Antoine, Pascal TI Phenomenological Reliving and Visual Imagery During Autobiographical Recall in Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; autobiographical memory; autonoetic consciousness; phenomenological reliving; visual imagery ID MILD COGNITIVE IMPAIRMENT; AUTONOETIC CONSCIOUSNESS; EPISODIC MEMORY; OLDER-ADULTS; DEMENTIA; MUSIC; RETRIEVAL; AMNESIA; SELF; OVERGENERALITY AB Multiple studies have shown compromise of autobiographical memory and phenomenological reliving in Alzheimer's disease (AD). We investigated various phenomenological features of autobiographical memory to determine their relative vulnerability in AD. To this aim, participants with early AD and cognitively normal older adult controls were asked to retrieve an autobiographical event and rate on a five-point scale metacognitive judgments (i.e., reliving, back in time, remembering, and realness), component processes (i.e., visual imagery, auditory imagery, language, and emotion), narrative properties (i.e., rehearsal and importance), and spatiotemporal specificity (i.e., spatial details and temporal details). AD participants showed lower general autobiographical recall than controls, and poorer reliving, travel in time, remembering, realness, visual imagery, auditory imagery, language, rehearsal, and spatial detail a decrease that was especially pronounced for visual imagery. Yet, AD participants showed high rating for emotion and importance. Early AD seems to compromise many phenomenological features, especially visual imagery, but also seems to preserve some other features. C1 [El Haj, Mohamad; Antoine, Pascal] Univ Lille, Lab SCALab, UMR CNRS 9193, F-59653 Villeneuve Dascq, France. [Kapogiannis, Dimitrios] NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP El Haj, M (reprint author), Univ Lille, Lab SCALab, Domaine Pont Bois, UMR CNRS 9193, F-59653 Villeneuve Dascq, France. EM mohamad.elhaj@univ-lille3.fr FU LABEX (excellence laboratory, program investment for the future); DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to Alzheimer disease) FX Dr. El Haj and Dr. Antoine were supported by the LABEX (excellence laboratory, program investment for the future) DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to Alzheimer disease). The authors would like to thank Lucille d'Hellemmes, Alexandra Carton, and Clementine Moreau for assistance in patients' recruitment and data collection. NR 60 TC 5 Z9 5 U1 3 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2016 VL 52 IS 2 BP 421 EP 431 DI 10.3233/JAD-151122 PG 11 WC Neurosciences SC Neurosciences & Neurology GA DN1PU UT WOS:000376838700004 PM 27003216 ER PT J AU Westwood, S Leoni, E Hye, A Lynham, S Khondoker, MR Ashton, NJ Kiddle, SJ Baird, AL Sainz-Fuertes, R Leung, R Graf, J Hehir, CT Baker, D Cereda, C Bazenet, C Ward, M Thambisetty, M Lovestone, S AF Westwood, Sarah Leoni, Emanuela Hye, Abdul Lynham, Steven Khondoker, Mizanur R. Ashton, Nicholas J. Kiddle, Steven J. Baird, Alison L. Sainz-Fuertes, Ricardo Leung, Rufina Graf, John Hehir, Cristina Tan Baker, David Cereda, Cristina Bazenet, Chantal Ward, Malcolm Thambisetty, Madhav Lovestone, Simon TI Blood-Based Biomarker Candidates of Cerebral Amyloid Using PiB PET in Non-Demented Elderly SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid; biological markers; blood; plasma; preclinical; proteomics ID ALZHEIMERS-DISEASE; BRAIN-BARRIER; FIBRINOGEN; INDIVIDUALS; ASSOCIATION; DEPOSITION; MARKERS; FLOW; AGE AB Increasingly, clinical trials for Alzheimer's disease (AD) are being conducted earlier in the disease phase and with biomarker confirmation using in vivo amyloid PET imaging or CSF tau and A beta measures to quantify pathology. However, making such a pre-clinical AD diagnosis is relatively costly and the screening failure rate is likely to be high. Having a blood-based marker that would reduce such costs and accelerate clinical trials through identifying potential participants with likely pre-clinical AD would be a substantial advance. In order to seek such a candidate biomarker, discovery phase proteomic analyses using 2DGE and gel-free LC-MS/MS for high and low molecular weight analytes were conducted on longitudinal plasma samples collected over a 12-year period from non-demented older individuals who exhibited a range of C-11-PiB PET measures of amyloid load. We then sought to extend our discovery findings by investigating whether our candidate biomarkers were also associated with brain amyloid burden in disease, in an independent cohort. Seven plasma proteins, including A2M, Apo-A1, and multiple complement proteins, were identified as pre-clinical biomarkers of amyloid burden and were consistent across three time points (p < 0.05). Five of these proteins also correlated with brain amyloid measures at different stages of the disease (q <0.1). Here we show that it is possible to detect a plasma based biomarker signature indicative of AD pathology at a stage long before the onset of clinical disease manifestation. As in previous studies, acute phase reactants and inflammatory markers dominate this signature. C1 [Westwood, Sarah; Baird, Alison L.; Lovestone, Simon] Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England. [Westwood, Sarah; Leoni, Emanuela; Hye, Abdul; Khondoker, Mizanur R.; Ashton, Nicholas J.; Sainz-Fuertes, Ricardo; Leung, Rufina; Bazenet, Chantal] Kings Coll London, Inst Psychiat Psychol & Neurosci, London WC2R 2LS, England. [Westwood, Sarah; Leoni, Emanuela; Hye, Abdul; Khondoker, Mizanur R.; Ashton, Nicholas J.; Sainz-Fuertes, Ricardo; Leung, Rufina; Bazenet, Chantal] South London & Maudsley NHS Fdn, NIHR Biomed Res Ctr Mental Hlth, London, England. [Westwood, Sarah; Leoni, Emanuela; Hye, Abdul; Khondoker, Mizanur R.; Ashton, Nicholas J.; Sainz-Fuertes, Ricardo; Leung, Rufina; Bazenet, Chantal] South London & Maudsley NHS Fdn, Biomed Res Unit Dementia, London, England. [Leoni, Emanuela] Univ Pavia, Dept Brain & Behav Sci, Via Palestro 3, I-27100 Pavia, Italy. [Leoni, Emanuela; Cereda, Cristina] C Mondino Natl Inst Neurol Fdn, Lab Expt Neurobiol, Pavia, Italy. [Lynham, Steven; Ward, Malcolm] Kings Coll London, Inst Psychiat, Ctr Excellence Mass Spectrometry, Prote Core Facil, London WC2R 2LS, England. [Khondoker, Mizanur R.] UCL, Dept Appl Hlth Res, London, England. [Kiddle, Steven J.] Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. [Sainz-Fuertes, Ricardo] North London Clin, Partnerships Care, London, England. [Graf, John; Hehir, Cristina Tan] GE Global Res, Diagnost Imaging & Biomed Technol, Niskayuna, NY USA. [Baker, David] Janssen R&D, Neurosci, Titusville, NJ USA. [Thambisetty, Madhav] NIA, Unit Clin & Translat Neurosci, Lab Behav Neurosci, Baltimore, MD 21224 USA. RP Lovestone, S (reprint author), Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. EM simon.lovestone@psych.ox.ac.uk RI CEREDA, CRISTINA/G-8208-2011; Khondoker, Mizanur/A-9860-2011; OI CEREDA, CRISTINA/0000-0001-9571-0862; Westwood, Sarah/0000-0003-0506-7813 FU Alzheimer's Society; Alzheimer's Research UK; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at the South London and Maudsley NHS Foundation Trust and Kings College London; Intramural Research Program of the NIH, National Institute on Aging; GE Healthcare; Janssen RD; MRC [MR/L011859/1] FX We are grateful for grant funding from the Alzheimer's Society, Alzheimer's Research UK, and the NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at the South London and Maudsley NHS Foundation Trust and Kings College London. We are grateful to participants in the Baltimore Longitudinal Study of Aging for their invaluable contribution. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. A portion of this work was funded by GE Healthcare and Janssen R&D. SJK is supported by an MRC Career Development Award in Biostatistics (MR/L011859/1). The authors acknowledge data used in the preparation of this article obtained from The Australian, Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) which is a collaboration between CSIRO, Edith Cowan University (ECU), The Florey Institute of Neuroscience and Mental Health (FINMH), National Ageing Research Institute (NARI) and Austin Health (http://www.AIBL.csiro.au). NR 34 TC 1 Z9 1 U1 2 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2016 VL 52 IS 2 BP 561 EP 572 DI 10.3233/JAD-151155 PG 12 WC Neurosciences SC Neurosciences & Neurology GA DN1PU UT WOS:000376838700014 PM 27031486 ER PT J AU Zanusso, G Bongianni, M Orru, C Groveman, B Sacchetto, L Fiorini, M Testi, S Cagnin, A Ladogana, A Colaizzo, E Pocchiari, M Monaco, S Caughey, B AF Zanusso, G. Bongianni, M. Orru, C. Groveman, B. Sacchetto, L. Fiorini, M. Testi, S. Cagnin, A. Ladogana, A. Colaizzo, E. Pocchiari, M. Monaco, S. Caughey, B. TI Accuracy of Creutzfeldt-Jakob disease diagnosis using RT-QUIC testing of olfactory mucosa and cerebrospinal fluid samples SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Meeting Abstract ID NASAL BRUSHINGS C1 [Zanusso, G.; Bongianni, M.; Fiorini, M.; Testi, S.; Monaco, S.] Univ Verona, Dept Neurol & Movement Sci, I-37100 Verona, Italy. [Orru, C.; Groveman, B.; Caughey, B.] NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT USA. [Sacchetto, L.] Azienda Osped Univ Integrata, Otorinolaryngol Unit, Verona, Italy. [Cagnin, A.] Univ Padua, Dept Neurosci, Padua, Italy. [Ladogana, A.; Colaizzo, E.; Pocchiari, M.] Ist Super Sanita, Dept Cell Biol & Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy. RI Ladogana, Anna/K-1415-2016 NR 3 TC 0 Z9 0 U1 1 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2016 VL 52 SU 1 BP S6 EP S6 PG 1 WC Neurosciences SC Neurosciences & Neurology GA DN5VB UT WOS:000377138200010 ER PT J AU Howard, LC Liu, CY Purdy, JB Walter, P Bluemke, DA Hadigan, C AF Howard, Louisa C. Liu, Chia-Ying Purdy, Julia B. Walter, Peter Bluemke, David A. Hadigan, Colleen TI Lipolytic Rate Associated With Intramyocardial Lipid in an HIV Cohort Without Increased Lipolysis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TYPE-2 DIABETES-MELLITUS; IMMUNODEFICIENCY-VIRUS-INFECTION; MYOCARDIAL TRIGLYCERIDE CONTENT; CARDIAC STEATOSIS; INSULIN-RESISTANCE; LIPODYSTROPHY; DISEASE; FAT; MEN; SPECTROSCOPY AB Context: Individuals with HIV have an elevated risk for developing cardiovascular disease compared to controls, particularly in relationship to abnormal deposition of lipid within various body compartments. Dysregulation of lipolysis may contribute to abnormal deposition of lipid in non-adipose tissues such as the heart, leading to untoward health consequences. Objective: To evaluate potential relationships between rates of whole-body lipolysis and intramyocardial lipid content in HIV-infected subjects compared to healthy controls. Design: Cross-sectional study. Setting: National Institutes of Health Clinical Research Center in Bethesda, Maryland. Participants: Forty-six HIV-infected adults and 12 controls without known cardiovascular disease. Main Outcome Measure: Intramyocardial lipid content quantified by MRI and rates of lipolysis determined using stable isotope tracer techniques. Results: We observed a significant positive correlation between the rate of appearance of glycerol and intramyocardial lipid overall (r = 0.323; P = .014) and among the HIV group separately (r = 0.361; P = .014). Multivariate regression analyses including HIV, lipid-lowering therapy, and diabetes identified both rate of appearance of glycerol and age as independent significant predictors of intramyocardial lipid (P = .01 and P = .03, respectively), but these were not significant with inclusion of visceral adipose in the analyses. Conclusions: To our knowledge, this study is among the first in humans to characterize the relationship between lipid deposition in the myocardium and direct measurement of whole-body fatty acid metabolism. Our current findings contribute to the growing understanding of factors that promote myocardial steatosis, such as visceral adiposity, and implicate lipolysis as a potential target for interventions to optimize myocardial health. C1 [Howard, Louisa C.; Hadigan, Colleen] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Liu, Chia-Ying; Bluemke, David A.] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Purdy, Julia B.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Walter, Peter] NIDDK, NIH, Bethesda, MD 20892 USA. RP Hadigan, C (reprint author), 10 Ctr Dr,Bldg 10,Room 11C103, Bethesda, MD 20189 USA. EM hadiganc@niaid.nih.gov OI Bluemke, David/0000-0002-8323-8086 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This research was supported by intramural funding from the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 27 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2016 VL 101 IS 1 BP 150 EP 155 DI 10.1210/jc.2015-3058 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DN6UT UT WOS:000377212700021 PM 26555936 ER PT J AU Shi, XG Liu, RY Basolo, F Giannini, R Shen, XP Teng, D Guan, HX Shan, ZY Teng, WP Musholt, TJ Al-Kuraya, K Fugazzola, L Colombo, C Kebebew, E Jarzab, B Czarniecka, A Bendlova, B Sykorova, V Sobrinho-Simoes, M Soares, P Shong, YK Kim, TY Cheng, S Asa, SL Viola, D Elisei, R Yip, L Mian, C Vianello, F Wang, YG Zhao, SH Oler, G Cerutti, JM Puxeddu, E Qu, S Wei, Q Xu, HX O'Neill, CJ Sywak, MS Clifton-Bligh, R Lam, AK Riesco-Eizaguirre, G Santisteban, P Yu, HY Tallini, G Holt, EH Vasko, V Xing, MZ AF Shi, Xiaoguang Liu, Rengyun Basolo, Fulvio Giannini, Riccardo Shen, Xiaopei Teng, Di Guan, Haixia Shan, Zhongyan Teng, Weiping Musholt, Thomas J. Al-Kuraya, Khawla Fugazzola, Laura Colombo, Carla Kebebew, Electron Jarzab, Barbara Czarniecka, Agnieszka Bendlova, Bela Sykorova, Vlasta Sobrinho-Simoes, Manuel Soares, Paula Shong, Young Kee Kim, Tae Yong Cheng, Sonia Asa, Sylvia L. Viola, David Elisei, Rossella Yip, Linwah Mian, Caterina Vianello, Federica Wang, Yangang Zhao, Shihua Oler, Gisele Cerutti, Janete M. Puxeddu, Efisio Qu, Shen Wei, Qing Xu, Huixiong O'Neill, Christine J. Sywak, Mark S. Clifton-Bligh, Roderick Lam, Alfred K. Riesco-Eizaguirre, Garcilaso Santisteban, Pilar Yu, Hongyu Tallini, Giovanni Holt, Elizabeth H. Vasko, Vasily Xing, Mingzhao TI Differential Clinicopathological Risk and Prognosis of Major Papillary Thyroid Cancer Variants SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BRAF V600E MUTATION; TALL-CELL VARIANT; NEEDLE-ASPIRATION BIOPSY; TERM-FOLLOW-UP; FOLLICULAR VARIANT; BRAF(V600E) MUTATION; SURGICAL-TREATMENT; CLINICAL-FEATURES; CARCINOMA; ASSOCIATION AB Context: Individualized management, incorporating papillary thyroid cancer (PTC) variant-specific risk, is conceivably a useful treatment strategy for PTC, which awaits comprehensive data demonstrating differential risks of PTC variants to support. Objective: This study sought to establish the differential clinicopathological risk of major PTC variants: conventional PTC (CPTC), follicular-variant PTC (FVPTC), and tall-cell PTC (TCPTC). Methods: This was a retrospective study of clinicopathological outcomes of 6282 PTC patients (4799 females and 1483 males) from 26 centers and The Cancer Genome Atlas in 14 countries with a median age of 44 years (interquartile range, 33-56 y) and median follow-up time of 37 months (interquartile range, 15-82 mo). Results: The cohort consisted of 4702 (74.8%) patients with CPTC, 1126 (17.9%) with FVPTC, and 239 (3.8%) with TCPTC. The prevalence of high-risk parameters was significantly different among the three variants, including extrathyroidal invasion, lymph node metastasis, stages III/IV, disease recurrence, mortality, and the use (need) of radioiodine treatment (all P < .001), being highest in TCPTC, lowest in FVPTC, and intermediate in CPTC, following an order of TCPTC > CPTC >> FVPTC. Recurrence and mortality in TCPTC, CPTC, and FVPTC were 27.3 and 6.7%, 16.1 and 2.5%, and 9.1 and 0.6%, corresponding to events per 1000 person-years (95% confidence interval [CI]) of 92.47 (64.66-132.26) and 24.61 (12.31-49.21), 34.46 (30.71-38.66), and 5.87 (4.37-7.88), and 24.73 (18.34-33.35) and 1.68 (0.54-5.21), respectively. Mortality hazard ratios of CPTC and TCPTC over FVPTC were 3.44 (95% CI, 1.07-11.11) and 14.96 (95% CI, 3.93-56.89), respectively. Kaplan-Meier survival analyses showed the best prognosis in FVPTC, worst in TCPTC, and intermediate in CPTC in disease recurrence-free probability and disease-specific patient survival. This was particularly the case in patients at least 45 years old. Conclusion: This large multicenter study demonstrates differential prognostic risks of the three major PTC variants and establishes a unique risk order of TCPTC > CPTC >> FVPTC, providing important clinical implications for specific variant-based management of PTC. C1 [Shi, Xiaoguang; Liu, Rengyun; Shen, Xiaopei; Teng, Di; Xing, Mingzhao] Johns Hopkins Univ, Sch Med, Div Endocrinol Diabet & Metab, Lab Cellular & Mol Thyroid Res,Dept Med, Baltimore, MD 21287 USA. [Basolo, Fulvio; Giannini, Riccardo] Dept Surg, Div Pathol, I-56126 Pisa, Italy. [Guan, Haixia; Shan, Zhongyan; Teng, Weiping] China Med Univ, Hosp 1, Endocrine Inst, Shenyang 110001, Liaoning, Peoples R China. [Guan, Haixia; Shan, Zhongyan; Teng, Weiping] China Med Univ, Hosp 1, Dept Endocrinol & Metab, Liaoning Prov Key Lab Endocrine Dis, Shenyang 110001, Liaoning, Peoples R China. [Musholt, Thomas J.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Endocrine Surg, D-55101 Mainz, Germany. [Al-Kuraya, Khawla] King Faisal Specialist Hosp & Res Ctr, Res Ctr, Human Canc Genom Res, Riyadh 12713, Saudi Arabia. [Fugazzola, Laura; Colombo, Carla] IRCCS Ca Granda Policlin, Fdn Inst Ricovero & Cura Carattere Sci, Milan, Italy. [Fugazzola, Laura; Colombo, Carla] Univ Milan, Dept Pathophysiol & Transplantat, I-20122 Milan, Italy. [Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Jarzab, Barbara; Czarniecka, Agnieszka] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, PL-44101 Gliwice, Poland. [Bendlova, Bela; Sykorova, Vlasta] Inst Endocrinol, Dept Mol Endocrinol, Prague 11694, Czech Republic. [Sobrinho-Simoes, Manuel; Soares, Paula] Univ Porto Ipatimup, Inst Mol Pathol & Immunol, P-4200319 Oporto, Portugal. [Sobrinho-Simoes, Manuel; Soares, Paula] Univ Porto, Fac Med, P-4200319 Oporto, Portugal. [Shong, Young Kee; Kim, Tae Yong] Univ Ulsan, Coll Med, Seoul, South Korea. [Cheng, Sonia; Asa, Sylvia L.] Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2C4, Canada. [Viola, David; Elisei, Rossella] Univ Pisa, WHO, Endocrine Unit,Dept Clin & Expt Med, Collaborating Ctr Study & Treatment Thyroid Dis &, I-56124 Pisa, Italy. [Yip, Linwah] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Mian, Caterina] Univ Padua, Endocrinol Unit, Dept Med, I-35128 Padua, Italy. [Vianello, Federica] IRCCS, Veneto Inst Oncol, I-35128 Padua, Italy. [Wang, Yangang; Zhao, Shihua] Qingdao Univ, Affiliated Hosp, Dept Endocrinol, Qingdao 266003, Peoples R China. [Oler, Gisele; Cerutti, Janete M.] Univ Fed Sao Paulo, Div Genet, Genet Bases Thyroid Tumor Lab, BR-04039032 Sao Paulo, Brazil. [Puxeddu, Efisio] Univ Perugia, Dept Internal Med, I-06100 Perugia, Italy. [Qu, Shen] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Endocrinol,Thyroid Inst, Shanghai 200072, Peoples R China. [Xu, Huixiong] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Med Ultrasound,Thyroid Inst, Shanghai 200072, Peoples R China. [O'Neill, Christine J.; Sywak, Mark S.; Clifton-Bligh, Roderick] Univ Sydney, Endocrine Surg Unit, Sydney, NSW 2052, Australia. [Lam, Alfred K.] Griffith Univ Gold Coast, Canc Mol Pathol Menzies Hlth Inst Queensland, Southport, Qld 4215, Australia. [Riesco-Eizaguirre, Garcilaso] Hosp La Paz, Hlth Res Inst, Madrid 28029, Spain. [Riesco-Eizaguirre, Garcilaso] Hosp Univ Mostoles, Madrid 28029, Spain. [Riesco-Eizaguirre, Garcilaso; Santisteban, Pilar] CSIC, Spanish Council Res, Biomed Res Inst, Alberto Sols, Madrid 28029, Spain. [Riesco-Eizaguirre, Garcilaso; Santisteban, Pilar] Autonomous Univ Madrid, Madrid 28029, Spain. [Yu, Hongyu] Second Mil Med Univ, Changzheng Hosp, Dept Pathol, Shanghai 200003, Peoples R China. [Tallini, Giovanni] Univ Bologna, Osped Bellaria, Anat Pathol Unit, Dept Med, I-40139 Bologna, Italy. [Holt, Elizabeth H.] Yale Univ, Sch Med, Dept Internal Med, Endocrine Sect, New Haven, CT 06520 USA. [Vasko, Vasily] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. RP Xing, MZ (reprint author), Johns Hopkins Univ, Sch Med, Div Endocrinol Diabet & Metab, 1830 East Monument St,Suite 333, Baltimore, MD 21287 USA. EM mxing1@jhmi.edu RI Giannini, Riccardo/K-4223-2013; Shen, Xiaopei /B-2773-2017; Kim, Tae Yong/C-1272-2009; Liu, Rengyun/C-7964-2014; Soares, Paula/B-6054-2008; OI Giannini, Riccardo/0000-0001-9740-0219; Shen, Xiaopei /0000-0002-0004-4228; Kim, Tae Yong/0000-0003-4982-4441; Liu, Rengyun/0000-0002-1408-2372; Soares, Paula/0000-0001-9607-6998; Riesco-Eizaguirre, Garcilaso/0000-0002-2608-6397; BASOLO, FULVIO/0000-0003-1657-5020 FU US National Institutes of Health (NIH) [RO1CA113507, R01CA189224]; National Science Centre Poland (Poland) [N403 194340, N N401 612440, 267398]; Queensland Government (Australia); Griffith Health Institute (Australia); Fondazione Cassa di Risparmio di Perugia (Italy); Associazione Italiana per la Ricerca sul Cancro (Italy) [IG 9338]; Beadle Family Foundation (San Antonio, TX); New South Wales Cancer Institute (Australia); Cancer Council of New South Wales (Australia); Italian Government-Ministero della Salute (Italy) [RF-2011-02350857]; Ministerodella Istruzione Universitaria e Ricerca Scientifica (Italy); AssociazioneItaliana per la Ricerca sul Cancro (Italy); Istituto Toscano Tumori (Italy); Ministero della Salute (Italy); Korean Foundation for Cancer Research (South Korea) [CB-2011-03-02]; Sao Paulo State Research Foundation (FAPESP) [2012/02902-9, 2013/03867-5]; AIRC (Italy) [IG 10316]; Shanghai Hospital Development Center (China) [SHDC 12014229]; Programa Operacional Regional do Norte (ON.2-O Novo Norte), under the Quadro de Referencia Estrategico Nacional; Fundo Europeu de Desenvolvimento Regional; [RD12/0036/0030 FIS-ISCIII]; [S2011/BMD-2328 TIRONET]; [SAF2013-44709-R]; [IGA MH CR NT 13901-4]; [NIH/NIA 5R03AG042334-02] FX This work was supported by the US National Institutes of Health (NIH) Grants No. RO1CA113507 and R01CA189224 (to M.X.). In addition, the studies at individual centers were supported as follows: National Science Centre Poland Grants No. N403 194340 and N N401 612440 to A.C. and B.J., respectively, and Milestone Grant No. 267398 to both (Poland); Grants from Queensland Government Smart State Fellowship and Griffith Health Institute to A.K.L. (Australia); Grants No. RD12/0036/0030 FIS-ISCIII, S2011/BMD-2328 TIRONET, and SAF2013-44709-R to P.So. (Spain); grants from Fondazione Cassa di Risparmio di Perugia and Associazione Italiana per la Ricerca sul Cancro (IG 9338) (Italy) and the Beadle Family Foundation (San Antonio, TX) to E.P.; Grant IGA MH CR NT 13901-4 to V.S. and B.B. (the Czech Republic); grants from the New South Wales Cancer Institute to C.J.O. and from Cancer Council of New South Wales to R.C.-B. (Australia); Italian Government-Ministero della Salute Grant No. RF-2011-02350857 to G.T. (Italy); Grant NIH/NIA 5R03AG042334-02 to L.Y. (United States); Grants from the Ministerodella Istruzione Universitaria e Ricerca Scientifica, the AssociazioneItaliana per la Ricerca sul Cancro, the Istituto Toscano Tumori, and the Ministero della Salute to D.V. and R.E (Italy); and Grant No. CB-2011-03-02 from the Korean Foundation for Cancer Research to Y.K.S. and T.Y.K. (South Korea); Research Grants 2012/02902-9 and 2013/03867-5 from The Sao Paulo State Research Foundation (FAPESP) to J.M.C. (G.O. is a FAPESP scholar and J.M.C. is a Brazilian Research Council investigator (Brazil); AIRC Grant No. IG 10316 to F.B. (Italy); Grant No. SHDC 12014229 from Shanghai Hospital Development Center to H.X. (China); Programa Operacional Regional do Norte (ON.2-O Novo Norte), under the Quadro de Referencia Estrategico Nacional, and through the Fundo Europeu de Desenvolvimento Regional to M.S.-S. and P.So. NR 54 TC 10 Z9 10 U1 1 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2016 VL 101 IS 1 BP 263 EP 273 DI 10.1210/jc.2015-2917 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DN6UT UT WOS:000377212700034 PM 26529630 ER PT J AU Cawley, NX Rathod, T Young, S Lou, H Birch, N Loh, YP AF Cawley, Niamh X. Rathod, Trushar Young, Sigrid Lou, Hong Birch, Nigel Loh, Y. Peng TI Carboxypeptidase E and Secretogranin III Coordinately Facilitate Efficient Sorting of Proopiomelanocortin to the Regulated Secretory Pathway in AtT20 Cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID DISULFIDE-BONDED LOOP; ADRENOCORTICOTROPIN PRODUCTION; PROHORMONE CONVERTASE-1; NEUROENDOCRINE CELLS; ATT-20 CELLS; RECEPTOR; GRANULES; EXPRESSION; MECHANISM; BINDING AB Proopiomelanocortin (POMC) is a multivalent prohormone that can be processed into at least 7 biologically active peptide hormones. Processing can begin in the trans-Golgi network (TGN) and continues in the secretory granules of the regulated secretory pathway (RSP). Sorting of POMC into these granules is a complex process. Previously, a membrane-associated form of carboxypeptidase E (CPE) was shown to bind to POMC and facilitate its trafficking into these granules. More recently, secretogranin III (SgIII) was also found to affect POMC trafficking. Here, we show by RNA silencing that CPE and SgIII play a synergistic role in the trafficking of POMC to granules of the RSP in AtT20 cells. Reduction of either protein resulted in increased constitutive secretion of POMC and chromogranin A, which was increased even further when both proteins were reduced together, indicative of missorting at the TGN. In SgIII-reduced cells, POMC accumulated in a compartment that cofractionated and colocalized with syntaxin 6, a marker of the TGN, on sucrose density gradients and in immunocytochemistry, respectively, indicating an accumulation of this protein in the presumed sorting compartment. Regulated secretion of ACTH, as a measure of sorting and processing of POMC in mature granules, was reduced in the SgIII down-regulated cells but was increased in the CPE down-regulated cells. These results suggest that multiple sorting systems exist, providing redundancy to ensure the important task of continuous and accurate trafficking of prohormones to the granules of the RSP for the production of peptide hormones. C1 [Cawley, Niamh X.; Rathod, Trushar; Young, Sigrid; Lou, Hong; Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. [Birch, Nigel] Univ Auckland, Sch Biol Sci, Ctr Brain Res, Auckland 1, New Zealand. [Birch, Nigel] Univ Auckland, Brain Res New Zealand, Auckland 1, New Zealand. RP Cawley, NX (reprint author), NICHD, NIH, Bldg 49,Room 6A76,49 Convent Dr, Bethesda, MD 20892 USA. EM cawleyn@mail.nih.gov OI Birch, Nigel/0000-0002-8417-3587 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health. NR 20 TC 2 Z9 2 U1 1 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JAN PY 2016 VL 30 IS 1 BP 37 EP 47 DI 10.1210/me.2015-1166 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DN6SI UT WOS:000377205900005 PM 26646096 ER PT J AU Hill, MJ Suzuki, S Segars, JH Kino, T AF Hill, Micah J. Suzuki, Shigeru Segars, James H. Kino, Tomoshige TI CRTC2 Is a Coactivator of GR and Couples GR and CREB in the Regulation of Hepatic Gluconeogenesis SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; CYCLIN-DEPENDENT KINASE-5; GLUCOCORTICOID-RECEPTOR; TRANSCRIPTION FACTOR; CLINICAL-IMPLICATIONS; CIRCADIAN-RHYTHM; SUBUNIT GENE; PROMOTER; BINDING; LIVER AB Glucocorticoid hormones play essential roles in the regulation of gluconeogenesis in the liver, an adaptive response that is required for the maintenance of circulating glucose levels during fasting. Glucocorticoids do this by cooperating with glucagon, which is secreted from pancreatic islets to activate the cAMP-signaling pathway in hepatocytes. The cAMP-response element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) is a coactivator known to be specific to CREB and plays a central role in the glucagon-mediated activation of gluconeogenesis in the early phase of fasting. We show here that CRTC2 also functions as a coactivator for the glucocorticoid receptor (GR). CRTC2 strongly enhances GR-induced transcriptional activity of glucocorticoid-responsive genes. CRTC2 physically interacts with the ligand-binding domain of the GR through a region spanning amino acids 561-693. Further, CRTC2 is required for the glucocorticoid-associated cooperative mRNA expression of the glucose-6-phosphatase, a rate-limiting enzyme for hepatic gluconeogenesis, by facilitating the attraction of GR and itself to its promoter region already occupied by CREB. CRTC2 is required for the maintenance of blood glucose levels during fasting in mice by enhancing the GR transcriptional activity on both the G6p and phosphoenolpyruvate carboxykinase (Pepck) genes. Finally, CRTC2 modulates the transcriptional activity of the progesterone receptor, indicating that it may influence the transcriptional activity of other steroid/nuclear receptors. Taken together, these results reveal that CRTC2 plays an essential role in the regulation of hepatic gluconeogenesis through coordinated regulation of the glucocorticoid/GR-and glucagon/CREB-signaling pathways on the key genes G6P and PEPCK. C1 [Hill, Micah J.; Suzuki, Shigeru; Segars, James H.; Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Hill, Micah J.] Walter Reed Natl Mil Med Ctr, Div Reprod Endocrinol & Infertil, Bethesda, MD 20889 USA. [Suzuki, Shigeru] Asahikawa Med Univ, Dept Pediat, Asahikawa, Hokkaido 0788510, Japan. [Segars, James H.] Johns Hopkins Sch Med, Dept Gynecol & Obstet, Div Reprod Sci & Womens Hlth Res, Baltimore, MD 21205 USA. [Kino, Tomoshige] Sidra Med & Res Ctr, Div Expt Biol, Dept Expt Therapeut, Doha 26999, Qatar. RP Kino, T (reprint author), Sidra Med & Res Ctr, Out Patient Clin, Div Expt Biol, Dept Expt Therapeut, 5th Floor,Room C5-340,POB 26999, Doha, Qatar. EM tkino@sidra.org FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; Sidra Medical and Research Center; Asahikawa Medical University FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health, and the Sidra Medical and Research Center. S.S. was supported by the Asahikawa Medical University. NR 46 TC 3 Z9 3 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JAN PY 2016 VL 30 IS 1 BP 104 EP 117 DI 10.1210/me.2015-1237 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DN6SI UT WOS:000377205900010 PM 26652733 ER PT J AU Liu, Y Wang, ZT Zhang, HM Lang, LX Ma, Y He, QJ Lu, N Huang, P Liu, YJ Song, JB Liu, ZB Gao, S Ma, QJ Kiesewetter, DO Chen, XY AF Liu, Yi Wang, Zhantong Zhang, Huimin Lang, Lixin Ma, Ying He, Qianjun Lu, Nan Huang, Peng Liu, Yijing Song, Jibin Liu, Zhibo Gao, Shi Ma, Qingjie Kiesewetter, Dale O. Chen, Xiaoyuan TI A photothermally responsive nanoprobe for bioimaging based on Edman degradation SO NANOSCALE LA English DT Article ID NEAR-INFRARED LIGHT; MESOPOROUS SILICA; UPCONVERTING NANOPARTICLES; GOLD NANOPARTICLES; PLASMONIC VESICLES; CONTROLLED-RELEASE; GUEST MOLECULES; HUMAN-CELLS; FLUORESCENCE; THERAPY AB A new type of photothermally responsive nanoprobe based on Edman degradation has been synthesized and characterized. Under irradiation by an 808 nm laser, the heat generated by the gold nanorod core breaks the thiocarbamide structure and releases the fluorescent dye Cy5.5 with increased near-infrared (NIR) fluorescence under mild acidic conditions. This RGD modified nanoprobe is capable of fluorescence imaging of alpha(nu)beta(3) over-expressing U87MG cells in vitro and in vivo. This Edman degradation-based nanoprobe provides a novel strategy to design activatable probes for biomedical imaging and drug/gene delivery. C1 [Liu, Yi; Gao, Shi; Ma, Qingjie] Jilin Univ, China Japan Union Hosp, Changchun 130033, Jilin, Peoples R China. [Liu, Yi; Wang, Zhantong; Zhang, Huimin; Lang, Lixin; Ma, Ying; He, Qianjun; Lu, Nan; Huang, Peng; Liu, Yijing; Song, Jibin; Liu, Zhibo; Kiesewetter, Dale O.; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Ma, QJ (reprint author), Jilin Univ, China Japan Union Hosp, Changchun 130033, Jilin, Peoples R China.; Kiesewetter, DO; Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM maqj@jlu.edu.cn; dkiesewetter@mail.nih.gov; shawn.chen@nih.gov RI Huang, Peng/R-2480-2016; HE, QIANJUN/M-2642-2013 OI Huang, Peng/0000-0003-3651-7813; HE, QIANJUN/0000-0003-0689-8838 FU National Natural Science Foundation of China (NSFC) [81571708, 81501506, 81401465, 51573096]; Research Fund of Science and Technology Department of Jilin Province [20150520154JH]; Hygiene Specific Subjects of Jilin Province [SCZSY201508]; National Institute of Biomedical Imaging and Bioengineering (NIBIB); National Institutes of Health (NIH) FX This research was supported by the National Natural Science Foundation of China (NSFC) projects (81571708, 81501506, 81401465 & 51573096), the Research Fund of Science and Technology Department of Jilin Province (20150520154JH), the Hygiene Specific Subjects of Jilin Province (SCZSY201508) and the intramural Research Programs of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), and the National Institutes of Health (NIH). NR 45 TC 2 Z9 2 U1 15 U2 31 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2016 VL 8 IS 20 BP 10553 EP 10557 DI 10.1039/c6nr01400c PG 5 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA DN5VX UT WOS:000377140700007 PM 27149392 ER PT J AU Hayman, DTS Pulliam, JRC Marshall, JC Cryan, PM Webb, CT AF Hayman, David T. S. Pulliam, Juliet R. C. Marshall, Jonathan C. Cryan, Paul M. Webb, Colleen T. TI Environment, host, and fungal traits predict continental-scale white-nose syndrome in bats SO SCIENCE ADVANCES LA English DT Article ID EVAPORATIVE WATER-LOSS; MYOTIS-LUCIFUGUS; BROWN BATS; GEOMYCES-DESTRUCTANS; HIBERNATING MAMMALS; MOISTURE REQUIREMENTS; SENSITIVITY-ANALYSIS; ENERGY-EXPENDITURE; MICROBIAL-GROWTH; BODY-TEMPERATURE AB White-nose syndrome is a fungal disease killing bats in eastern North America, but disease is not seen in European bats and is less severe in some North American species. We show that how bats use energy during hibernation and fungal growth rates under different environmental conditions can explain how some bats are able to survive winter with infection and others are not. Our study shows how simple but nonlinear interactions between fungal growth and bat energetics result in decreased survival times at more humid hibernation sites; however, differences between species such as body size and metabolic rates determine the impact of fungal infection on bat survival, allowing European bat species to survive, whereas North American species can experience dramatic decline. C1 [Hayman, David T. S.; Marshall, Jonathan C.] Massey Univ, Hopkirk Res Inst, Mol Epidemiol & Publ Hlth Lab, Private Bag 11 222, Palmerston North 4442, New Zealand. [Pulliam, Juliet R. C.] Univ Florida, Dept Biol, Gainesville, FL 32611 USA. [Pulliam, Juliet R. C.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA. [Pulliam, Juliet R. C.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. [Marshall, Jonathan C.] Massey Univ, Inst Fundamental Sci, Private Bag 11 222, Palmerston North 4442, New Zealand. [Cryan, Paul M.] US Geol Survey, Ft Collins Sci Ctr, Ft Collins, CO 80526 USA. [Webb, Colleen T.] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. RP Hayman, DTS (reprint author), Massey Univ, Hopkirk Res Inst, Mol Epidemiol & Publ Hlth Lab, Private Bag 11 222, Palmerston North 4442, New Zealand. EM d.t.s.hayman@massey.ac.nz NR 91 TC 4 Z9 4 U1 14 U2 19 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 2375-2548 J9 SCI ADV JI Sci. Adv. PD JAN PY 2016 VL 2 IS 1 AR e1500831 DI 10.1126/sciadv.1500831 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DN3OU UT WOS:000376972900005 PM 27152322 ER PT J AU Mitra, A Mukhopadhyay, S AF Mitra, Arindam Mukhopadhyay, Suman TI Biofilm mediated decontamination of pollutants from the environment SO AIMS BIOENGINEERING LA English DT Review DE bioremediation; biofilms; in situ bioremediation; pollution control; biodegradation; wastewater treatment; biofilm reactors ID POLYCYCLIC AROMATIC-HYDROCARBONS; ROTATING BIOLOGICAL CONTACTOR; EXTRACELLULAR POLYMERIC SUBSTANCES; REDUCING BACTERIAL BIOFILMS; EXOPOLYSACCHARIDE-PRODUCING CYANOBACTERIA; WASTE-WATER TREATMENT; HEAVY-METAL REMOVAL; NATURAL ATTENUATION; COMMUNITY STRUCTURE; MICROBIAL BIOFILMS AB In this review, we highlight beneficial use of microbial biofilms in remediation of environmental pollutants by bioremediation. Bioremediation is an environment friendly, cost effective, sustainable technology that utilizes microbes to decontaminate and degrade a wide variety of pollutants into less harmful products. Relative to free-floating planktonic cells, microbes existing in biofilm mode are advantageous for bioremediation because of greater tolerance to pollutants, environmental stress and ability to degrade varied harsh pollutants via diverse catabolic pathways. In biofilm mode, microbes are immobilized in a self-synthesized matrix which offers protection from stress, contaminants and predatory protozoa. Contaminants ranging from heavy metals, petroleum, explosives, pesticides have been remediated using microbial consortia of biofilms. In the industry, biofilm based bioremediation is used to decontaminate polluted soil and groundwater. Here we discuss conventional and newer strategies utilizing biofilms in environmental remediation. C1 [Mitra, Arindam] Adamas Univ, Dept Microbiol, Kolkata 700126, W Bengal, India. [Mukhopadhyay, Suman] NIAID, Div Microbiol & Infect Dis, NIH, HHS, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Mitra, A (reprint author), Adamas Univ, Dept Microbiol, Kolkata 700126, W Bengal, India. EM arindam.mitra@adamasuniversity.ac.in NR 136 TC 1 Z9 1 U1 15 U2 28 PU AMER INST MATHEMATICAL SCIENCES-AIMS PI SPRINGFIELD PA PO BOX 2604, SPRINGFIELD, MO 65801-2604 USA SN 2375-1495 J9 AIMS BIOENG JI AIMS Bioeng. PY 2016 VL 3 IS 1 BP 44 EP 59 DI 10.3934/bioeng.2016.1.44 PG 16 WC Engineering, Biomedical SC Engineering GA DM5PI UT WOS:000376401700003 ER PT J AU Sun, JEP Stewart, B Litan, A Lee, SJ Schneider, JP Langhans, SA Pochan, DJ AF Sun, Jessie E. P. Stewart, Brandon Litan, Alisa Lee, Seung Joon Schneider, Joel P. Langhans, Sigrid A. Pochan, Darrin J. TI Sustained release of active chemotherapeutics from injectable-solid beta-hairpin peptide hydrogel SO BIOMATERIALS SCIENCE LA English DT Article ID DRUG-DELIVERY; DESIGNED PEPTIDE; VINCRISTINE SULFATE; STEM-CELLS; IN-VITRO; CANCER; NANOPARTICLES; LYMPHOMA; THERAPY; BIOMATERIALS AB MAX8 beta-hairpin peptide hydrogel is a solid, preformed gel that can be syringe injected due to shear-thinning properties and can recover solid gel properties immediately after injection. This behavior makes the hydrogel an excellent candidate as a local drug delivery vehicle. In this study, vincristine, a hydrophobic and commonly used chemotherapeutic, is encapsulated within MAX8 hydrogel and shown to release constantly over the course of one month. Vincristine was observed to be cytotoxic in vitro at picomolar to nanomolar concentrations. The amounts of drug released from the hydrogels over the entire time-course were in this concentration range. After encapsulation, release of vincristine from the hydrogel was observed for four weeks. Further characterization showed the vincristine released during the 28 days remained biologically active, well beyond its half-life in bulk aqueous solution. This study shows that vincristine-loaded MAX8 hydrogels are excellent candidates as drug delivery vehicles, through sustained, low, local and effective release of vincristine to a specific target. Oscillatory rheology was employed to show that the shear-thinning and re-healing, injectable-solid properties that make MAX8 a desirable drug delivery vehicle are unaffected by vincristine encapsulation. Rheology measurements also were used to monitor hydrogel nanostructure before and after drug encapsulation. C1 [Sun, Jessie E. P.; Stewart, Brandon; Pochan, Darrin J.] Univ Delaware, Dept Mat Sci & Engn, Newark, DE 19176 USA. [Litan, Alisa; Lee, Seung Joon; Langhans, Sigrid A.] Nemours AI duPont Hosp Children, Nemours Ctr Childhood Canc Res, Wilmington, DE 19803 USA. [Schneider, Joel P.] NCI, Ctr Canc Res, NIH, Frederick, MD 21701 USA. RP Pochan, DJ (reprint author), Univ Delaware, Dept Mat Sci & Engn, Newark, DE 19176 USA. EM pochan@udel.edu FU University of Delaware's NIH Center of Biomedical Research Excellence, entitled Molecular Design of Advanced Biomaterials [P20-RR017716]; Nemours Foundation; National Institute of General Medical Sciences - NIGMS from the National Institutes of Health [1 P30 GM110758-01] FX This work was funded by a seed grant from the University of Delaware's NIH Center of Biomedical Research Excellence, entitled Molecular Design of Advanced Biomaterials (P20-RR017716) and the Nemours Foundation. Research facilities were supported in part by the current Delaware COBRE program, supported by a grant from the National Institute of General Medical Sciences - NIGMS (1 P30 GM110758-01) from the National Institutes of Health. We acknowledge the support of the National Institute of Standards and Technology, U.S. Department of Commerce, in providing the neutron research facilities used in this work. This work utilized facilities supported in part by the National Science Foundation under Agreement no. DMR-0944772. This manuscript was prepared under cooperative agreement 70NANB12H239 from NIST, U.S. Department of Commerce. The statements, findings, conclusions, and recommendations are those of the authors and do not necessarily reflect the view of NIST or the U.S. Department of Commerce. NR 72 TC 5 Z9 5 U1 13 U2 21 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2047-4830 EI 2047-4849 J9 BIOMATER SCI-UK JI Biomater. Sci. PY 2016 VL 4 IS 5 BP 839 EP 848 DI 10.1039/c5bm00538h PG 10 WC Materials Science, Biomaterials SC Materials Science GA DK7UY UT WOS:000375132800008 PM 26906463 ER PT J AU Ortiz, R Hull, SC Colloca, L AF Ortiz, Robin Hull, Sara Chandros Colloca, Luana TI Patient attitudes about the clinical use of placebo: qualitative perspectives from a telephone survey SO BMJ OPEN LA English DT Article ID GENERAL-PRACTICE; HEALTH LITERACY; EXPECTATIONS; PATERNALISM; EDUCATION; MEDICINE; ETHICS; GPS; LIE AB Objectives: To examine qualitative responses regarding the use of placebo treatments in medical care in a sample of US patients. Survey studies suggest a deliberate clinical use of placebos by physicians, and prior research has found that although most US patients find placebo use acceptable, the rationale for these beliefs is largely unknown. Setting: Members of the Outpatient Clinic at the Kaiser Permanente Northern California interviewed research participants who had been seen for a chronic health problem at least once in the prior 6 months. Participants: 853 women (61%) and men, white (58%) and non-white participants aged 18-75 years. Primary and secondary outcomes: Qualitative responses on perceptions of placebo use from one-time telephone surveys were analysed for common themes and associations with demographic variables. Results: Prior results indicated that a majority of respondents felt it acceptable for doctors to recommend placebo treatments. Our study found that a lack of harm (n=291, 46.1%) and potential benefit (n= 250, 39.6%) were the most common themes to justify acceptability of placebo use. Responses citing potential benefit were associated with higher education (r= 0.787; p< 0.024). Of the minority of respondents who judged it never acceptable for doctors to recommend placebo treatments, the most often referenced rationale was obligation of the doctor to do more (n= 102, 48.3%). Additional themes emerged around the issue of whether a doctor was transparent about placebo use, including honesty, patient's right to know and power of the mind. Older age was associated with likelihood to cite overall physician, as opposed to treatment, related themes (r= 0.753; p< 0.002). Conclusions: Participants seem to appreciate and understand the lack of harm and potential benefit associated with placebo treatments, while valuing the role of the physician and the patient in its implementation. C1 [Ortiz, Robin] Johns Hopkins Univ Hosp, Med Pediat Residency Program, Baltimore, MD 21287 USA. [Ortiz, Robin; Hull, Sara Chandros] NIH, Bldg 10, Bethesda, MD 20892 USA. [Hull, Sara Chandros] NHGRI, Dept Bioeth, Off Sci Director, Ctr Clin,NIH, Bethesda, MD 20892 USA. [Colloca, Luana] Univ Maryland, Sch Nursing, Ctr Adv Chron Pain Res CACPR, Dept Pain Translat Symptom Sci, Baltimore, MD 21201 USA. [Colloca, Luana] Univ Maryland, Sch Nursing, Ctr Adv Chron Pain Res CACPR, Sch Med,Dept Anesthesiol, Baltimore, MD 21201 USA. RP Colloca, L (reprint author), Univ Maryland, Sch Nursing, Ctr Adv Chron Pain Res CACPR, Dept Pain Translat Symptom Sci, Baltimore, MD 21201 USA.; Colloca, L (reprint author), Univ Maryland, Sch Nursing, Ctr Adv Chron Pain Res CACPR, Sch Med,Dept Anesthesiol, Baltimore, MD 21201 USA. EM colloca@son.umaryland.edu FU National Center for Complementary and Integrative Health; Clinical Center, the Intramural Research Program of the National Human Genome Research Institute; National Institutes of Health; National Institute of Dental and Craniofacial Research [1R01DE025946-01]; University of Maryland Baltimore FX This research was supported by the National Center for Complementary and Integrative Health (LC and SCH), the Clinical Center, the Intramural Research Program of the National Human Genome Research Institute (SCH), National Institutes of Health (RO), the National Institute of Dental and Craniofacial Research (1R01DE025946-01, LC) and the University of Maryland Baltimore (LC). The opinions expressed are those of the authors and do not necessarily reflect the policies or views of the National Institutes of Health or the Department of Health and Human Services. The study funders played no role in the study design; collection, analysis, and interpretation of data; writing of the report; or the decision to submit the article for publication. Researchers were independent of influence from study funders. NR 33 TC 0 Z9 0 U1 3 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2016 VL 6 IS 4 AR e011012 DI 10.1136/bmjopen-2015-011012 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA DM5LV UT WOS:000376391400132 PM 27044586 ER PT J AU Leary, J Levy, S McNally, S Pham, D Chou, YY Constantin, A Dsurney, J Chan, L AF Leary, Jacob Levy, Sarah McNally, Shannon Dzung Pham Chou, Yi-Yu Constantin, Alex Dsurney, John Chan, Leighton TI Longitudinal changes in brain volume over the first year following traumatic brain injury SO BRAIN INJURY LA English DT Meeting Abstract C1 [Leary, Jacob; Constantin, Alex; Chan, Leighton] NIH, Bldg 10, Bethesda, MD 20892 USA. [Levy, Sarah] Suffolk Univ, Boston, MA 02114 USA. [McNally, Shannon; Dzung Pham; Chou, Yi-Yu; Dsurney, John] Ctr Neurosci & Regenerat Med, Rockville, MD 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 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PY 2016 VL 30 IS 5-6 MA 0140 BP 528 EP 529 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200114 ER PT J AU Politis, A Turkstra, L AF Politis, Adam Turkstra, Lyn TI A complex dynamical systems approach to analysis of conversational discourse in traumatic brain injury SO BRAIN INJURY LA English DT Meeting Abstract C1 [Politis, Adam] NIH, Bldg 10, Bethesda, MD 20892 USA. [Turkstra, Lyn] Univ Wisconsin, Madison, WI USA. NR 2 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 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PY 2016 VL 30 IS 5-6 MA 0642 BP 730 EP 731 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200554 ER PT J AU Prasanna, P AF Prasanna, Pataje TI Radiation-induced brain damage and the need for prredictive biomarkers SO BRAIN INJURY LA English DT Meeting Abstract C1 [Prasanna, Pataje] NCI, Bethesda, MD 20892 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 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PY 2016 VL 30 IS 5-6 MA 0742 BP 768 EP 769 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DM5KP UT WOS:000376388200638 ER PT J AU Lee, C Pearce, MS Salotti, JA Harbron, RW Little, MP Mchugh, K Chapple, CL De Gonzalez, AB AF Lee, Choonsik Pearce, Mark S. Salotti, Jane A. Harbron, Richard W. Little, Mark P. Mchugh, Kieran Chapple, Claire-Louise De Gonzalez, Amy Berrington TI Reduction in radiation doses from paediatric CT scans in Great Britain SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID TUBE CURRENT MODULATION; AVAILABLE OPTIONS; CANCER; COHORT; RISK; SIMULATION; DOSIMETRY; EXPOSURE AB Objective: Although CT scans provide great medical benefits, concerns have been raised about the magnitude of possible associated cancer risk, particularly in children who are more sensitive to radiation than adults. Unnecessary high doses during CT examinations can also be delivered to children, if the scan parameters are not adjusted for patient age and size. We conducted the first survey to directly assess the trends in CT scan parameters and doses for paediatric CT scans performed in Great Britain between 1978 and 2008. Methods: We retrieved 1073 CT film sets from 36 hospitals. The patients were 0-19 years old, and CT scans were conducted between 1978 and 2008. We extracted scan parameters from each film including tube current-time product [milliampere seconds (mAs)], tube potential [peak kilovoltage (kVp)] and manufacturer and model of the CT scanner. We estimated the mean mAs for head and trunk (chest and abdomen/pelvis) scans, according to patient age (0-4, 5-9, 10-14 and 15-19 years) and scan year (<1990, 1990-1994, 1995-1999 and >= 2000), and then derived the volumetric CT dose index and estimated organ doses. Results: For head CT scans, mean mAs decreased by about 47% on average from before 1990 to after 2000, with the decrease starting around 1990. The mean mAs for head CTs did not vary with age before 1990, whereas slightly lower mAs values were used for younger patients after 1990. Similar declines in mAs were observed for trunk CTs: a 46% decline on an average from before 1990 to after 2000. Although mean mAs for trunk CTs did not vary with age before 1990, the value varied markedly by age, from 63mAs for age 0-4 years compared with 315mAs for those aged >15 years after 2000. No material changes in kVp were found. Estimated brain-absorbed dose from head CT scans decreased from 62mGy before 1990 to approximately 30mGy after 2000. For chest CT scans, the lung dose to children aged 0-4 years decreased from 28mGy before 1990 to 4mGy after 2000. Conclusion: We found that mAs for head and trunk CTs was approximately halved starting around 1990, and age-specific mAs was generally used for paediatric scans after this date. These changes will have substantially reduced the radiation exposure to children from CT scans in Great Britain. Advances in knowledge: The study shows that mAs and major organ doses for paediatric CT scans in Great Britain began to decrease around 1990. C1 [Lee, Choonsik; Little, Mark P.; De Gonzalez, Amy Berrington] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Pearce, Mark S.; Salotti, Jane A.; Harbron, Richard W.] Newcastle Univ, Royal Victoria Infirm, Inst Hlth & Soc, Sir James Spence Inst, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Mchugh, Kieran] Great Ormond St Hosp Sick Children, Great Ormond St, London WC1N 3JH, England. [Chapple, Claire-Louise] NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England. RP Lee, C (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM leechoonsik@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 29 TC 4 Z9 4 U1 0 U2 1 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 EI 1748-880X J9 BRIT J RADIOL JI Br. J. Radiol. PY 2016 VL 89 IS 1060 AR 20150305 DI 10.1259/bjr.20150305 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DM6UK UT WOS:000376487900004 PM 26864156 ER PT J AU Kamal, MA Greig, NH AF Kamal, Mohammad A. Greig, Nigel H. TI Editorial Managing Strategies for Diverse Diseases: Challenges from Bench to Bedside Translation in Successful Drug Discovery and Development (Part B) SO CURRENT PHARMACEUTICAL DESIGN LA English DT Editorial Material C1 [Kamal, Mohammad A.] King Abdulaziz Univ, King Fahd Med Res Ctr, Metabol & Enzymol Unit, Fundamental & Appl Biol Grp, POB 80216, Jeddah 21589, Saudi Arabia. [Kamal, Mohammad A.] Enzymoics, 7 Peterlee Pl, Hebersham, NSW 2770, Australia. [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH,Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. RP Kamal, MA (reprint author), King Abdulaziz Univ, King Fahd Med Res Ctr, Metabol & Enzymol Unit, Fundamental & Appl Biol Grp, POB 80216, Jeddah 21589, Saudi Arabia.; Kamal, MA (reprint author), Enzymoics, 7 Peterlee Pl, Hebersham, NSW 2770, Australia.; Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH,Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM prof.makamal@lycos.com; greign@grc.nia.nih.gov OI Kamal, Mohammad Amjad/0000-0003-0088-0565 NR 10 TC 1 Z9 1 U1 1 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2016 VL 22 IS 20 BP 2923 EP 2925 DI 10.2174/1381612822666160411144843 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DM6HT UT WOS:000376453000001 PM 27063488 ER PT S AU Provencal, N Massart, R Nemoda, ZA Suomi, S AF Provencal, Nadine Massart, Renaud Nemoda, Zsofi A. Suomi, Stephen BE Spengler, D Binder, E TI Alterations in DNA Methylation and Hydroxymethylation Due to Parental Care in Rhesus Macaques SO EPIGENETICS AND NEUROENDOCRINOLOGY: CLINICAL FOCUS ON PSYCHIATRY, VOL 1 SE Epigenetics and Human Health LA English DT Article; Book Chapter DE DNA methylation; DNA hydroxymethylation; Parental care; Rhesus macaques; G x E; Genetic and Epigenetic ID EARLY-LIFE STRESS; SEROTONIN TRANSPORTER GENE; NONHUMAN PRIMATE MODELS; T-CELL DEVELOPMENT; EPIGENETIC REGULATION; MATERNAL-CARE; HUMAN BRAIN; ENVIRONMENT INTERACTIONS; GLUCOCORTICOID-RECEPTOR; INDIVIDUAL-DIFFERENCES AB Early life is one of the most important and sensitive periods during the development of an individual. During this stage, the body and especially the brain are known to be greatly responsive to environmental cues, such as the early social environment. As a consequence, early life adverse social experiences in humans are associated with a wide range of health problems in adulthood. The broad range of phenotypes associated with early life stress (ELS) suggests a system-wide response of the organism, which is yet to be determined. In the last decade, increasing evidence suggests that epigenetic mechanisms underlie the effects of ELS on adult human health. However, there are critical challenges in delineating the direct effects of ELS on epigenetic profiles and phenotypes in human studies. It is impossible to randomize ELS and rare are the studies where complete information about past environmental insults is available, which would allow us to conclude on causality. Nonhuman primates offer several advantages in addressing these challenges. This chapter focuses on parental deprivation models in rhesus macaques which have been shown to produce an array of behavioral, physiological, and neurobiological deficits that parallel those identified in humans subjected to ELS. It describes the evidence for epigenetic alterations induced by differential rearing in this model and points out the differences between tissue-specific versus multi-tissue changes and outlines possible mechanisms for these to occur. In addition, it highlights the need for multi-omics longitudinal studies to better understand the epigenetic trajectories induced by ELS exposure and their impact on adult health. C1 [Provencal, Nadine] Max Planck Inst Psychiat, Dept Translat Res Psychiat, Kraepelinstr 2-10, D-80804 Munich, Germany. [Massart, Renaud; Nemoda, Zsofi A.] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada. [Massart, Renaud] CNRS, Epigenet & Cell Fate UMR7216, F-75205 Paris 13, France. [Nemoda, Zsofi A.] Semmelweis Univ, Inst Med Chem Mol Biol & Pathobiochem, H-1085 Budapest, Hungary. [Suomi, Stephen] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Bethesda, MD USA. RP Provencal, N (reprint author), Max Planck Inst Psychiat, Dept Translat Res Psychiat, Kraepelinstr 2-10, D-80804 Munich, Germany. EM nadine_provencal@psych.mpg.de NR 142 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2191-2262 BN 978-3-319-24493-8; 978-3-319-24491-4 J9 EPIGENETICS HUM HLTH PY 2016 BP 165 EP 190 DI 10.1007/978-3-319-24493-8_7 D2 10.1007/978-3-319-24493-8 PG 26 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA BE8KD UT WOS:000376527400008 ER PT J AU Gao, J Swain, SM AF Gao, Jennifer Swain, Sandra M. TI Pertuzumab for the treatment of breast cancer: a safety review SO EXPERT OPINION ON DRUG SAFETY LA English DT Review DE Pertuzumab; trastuzumab; monoclonal antibody; HER2; CLEOPATRA; TRYPHAENA; NeoSphere ID III TRIAL CLEOPATRA; TRASTUZUMAB PLUS DOCETAXEL; CONTROLLED PHASE-III; DIMERIZATION INHIBITOR; CARDIAC TOXICITY; SOLID TUMORS; DOUBLE-BLIND; OPEN-LABEL; GROWTH; DIARRHEA AB Introduction: Approximately twenty to thirty percent of newly diagnosed breast cancers are human epidermal growth factor receptor 2 (HER2) positive. The use of trastuzumab, and more recently pertuzumab, has significantly improved the progression free survival (PFS) and overall survival (OS) in this patient population. However, pertuzumab has side effects that can impact treatment tolerability and quality of life. Areas covered: This review describes the safety and tolerability of pertuzumab, a monoclonal antibody targeted at HER2 approved by the United States Food and Drug Administration (FDA) for use in the neoadjuvant and first line metastatic settings. Expert opinion: The combination of trastuzumab, pertuzumab, and chemotherapy is approved in the neoadjuvant and first line metastatic settings and should be strongly considered by providers. Further studies are needed to look at side effect prevention, novel pertuzumab containing regimens, and retreating patients with pertuzumab. C1 [Gao, Jennifer] NCI, Dept Med Oncol Serv, NIH, Bethesda, MD 20892 USA. [Swain, Sandra M.] MedStar Washington Hosp Ctr, Washington Canc Inst, 110 Irving St NW, Washington, DC 20010 USA. RP Swain, SM (reprint author), MedStar Washington Hosp Ctr, Washington Canc Inst, 110 Irving St NW, Washington, DC 20010 USA. EM sandra.m.swain@medstar.net OI Swain, Sandra/0000-0002-1320-3830 FU Genentech FX S Swain has received honorarium and consulting and travel compensation from Genentech/Roche. S Swain's institution has received research funding from Genentech. 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 46 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1474-0338 EI 1744-764X J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PY 2016 VL 15 IS 6 BP 853 EP 863 DI 10.1517/14740338.2016.1167185 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DM7GR UT WOS:000376526100014 PM 26982349 ER PT B AU Brown, P Cardone, F Meyer, R Pocchiari, M AF Brown, Paul Cardone, Franco Meyer, Richard Pocchiari, Maurizio BE Balasubramaniam, VM BarbosaCanovas, GV Lelieveld, HLM TI High-Pressure Inactivation of Transmissible Spongiform Encephalopathy Agents (Prions) in Processed Meats SO HIGH PRESSURE PROCESSING OF FOOD: PRINCIPLES, TECHNOLOGY AND APPLICATIONS SE Food Engineering Series LA English DT Article; Book Chapter DE High pressure; Prion; Bovine spongiform encephalopathy; Food safety ID CREUTZFELDT-JAKOB-DISEASE; PRODUCTS; INFECTIVITY; QUALITY; CATTLE AB The epidemic of bovine spongiform encephalopathy (BSE) that began in the late 1980s and has so far been responsible for over 200 human fatalities caused by the ingestion of contaminated beef products stimulated research into disinfection methods appropriate for both animal feed and human food. As it turned out, the risk of infection was almost entirely eliminated by government and industry bans, first on the use of recycled bovine tissues in cattle feed (the source of the epidemic in bovines) and, second, the exclusion of potentially contaminated bovine tissues from beef products consumed by humans. A third approach, had the first two not been successful, was a disinfection method compatible with the aesthetic and nutritional quality of beef products. In this chapter, we review the results of a series of experiments that were undertaken to explore optimal conditions for the commercial use of a combined high-temperature and high-pressure inactivation of BSE prions in processed meats. In repeated experiments, we were unable to detect any significant effect on infectivity from a two-hour exposure to 60 degrees C at pressures between 400 and 800 MPa. In a further large series of experiments conducted with a variety of machines at different facilities, we found that a 5-min exposure to temperatures and pressures in the range of 120-130 degrees C and 600-700 MPa yielded, on average, a 100-fold (2 log) reduction in infectivity. Depending on assumptions about the potential infectious load in a given beef product, this level of disinfection, although useful, cannot be guaranteed to eliminate the risk of disease transmission to humans. C1 [Brown, Paul] NIH, Bldg 10, Bethesda, MD 20892 USA. [Cardone, Franco; Pocchiari, Maurizio] Ist Super Sanita, Viale Regina Elena 299, I-00161 Rome, Italy. [Meyer, Richard] JCR Technol LLC, 62934 South Powderhorn Bay Rd, Harrison, ID 83833 USA. EM paulwbrown@comcast.net NR 17 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4939-3234-4; 978-1-4939-3233-7 J9 FOOD ENG SER PY 2016 BP 317 EP 330 DI 10.1007/978-1-4939-3234-4_16 D2 10.1007/978-1-4939-3234-4 PG 14 WC Food Science & Technology SC Food Science & Technology GA BE4MF UT WOS:000371921200017 ER PT S AU Woodford, MR Dunn, D Miller, JB Jamal, S Neckers, L Mollapour, M AF Woodford, Mark R. Dunn, Diana Miller, Jonelle B. Jamal, Sami Neckers, Len Mollapour, Mehdi BE Isaacs, J Whitesell, L TI Impact of Posttranslational Modifications on the Anticancer Activity of Hsp90 Inhibitors SO HSP90 IN CANCER: BEYOND THE USUAL SUSPECTS SE Advances in Cancer Research LA English DT Review; Book Chapter ID MOLECULAR CHAPERONE HSP90; BREAST-CANCER CELLS; CO-CHAPERONES; TYROSINE PHOSPHORYLATION; PROTEIN; BINDING; KINASE; COMPLEX; DOMAIN; PROLIFERATION AB Molecular chaperones are essential for guarding proteins that are indispensable for normal cellular functions. Heat shock protein 90 (Hsp90) is a vital molecular chaperone in eukaryotes that participates in stabilizing and activating approximately 200 target proteins, called "clients," many of which are involved in signal transduction pathways. Cancer cells however utilize Hsp90 to chaperone an array of mutated and overexpressed oncoproteins to protect them from misfolding and degradation. Therefore, Hsp90 is an attractive target in cancer therapy. Hsp90 chaperone function relies on ATP binding and hydrolysis, which in turn guides its carefully orchestrated conformational changes. This chaperone cycle is fine-tuned by another group of proteins called co-chaperones. They are able to accelerate or decelerate the cycle, allowing Hsp90 to chaperone different clients. Posttranslational modifications (PTMs) can also regulate the chaperone cycle at an epigenetic level thereby tailoring Hsp90 function to suit a specific cell type or environmental condition. Recent evidence suggests that inhibition of the enzymes that catalyze the PTM of Hsp90 can act synergistically with Hsp90 inhibitors, providing a novel therapeutic strategy to enhance the efficacy of Hsp90 inhibitors in cancer cells. C1 [Woodford, Mark R.; Dunn, Diana; Miller, Jonelle B.; Jamal, Sami; Mollapour, Mehdi] SUNY Upstate Med Univ, Dept Urol, Syracuse, NY 13210 USA. [Dunn, Diana; Mollapour, Mehdi] SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA. [Woodford, Mark R.; Dunn, Diana; Miller, Jonelle B.; Jamal, Sami; Mollapour, Mehdi] SUNY Upstate Med Univ, Canc Res Inst, Syracuse, NY 13210 USA. [Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Mollapour, M (reprint author), SUNY Upstate Med Univ, Dept Urol, Syracuse, NY 13210 USA.; Mollapour, M (reprint author), SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA.; Mollapour, M (reprint author), SUNY Upstate Med Univ, Canc Res Inst, Syracuse, NY 13210 USA. EM mollapom@upstate.edu OI Woodford, Mark/0000-0002-6737-2832 NR 40 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X BN 978-0-12-802483-6 J9 ADV CANCER RES JI Adv.Cancer Res. PY 2016 VL 129 BP 31 EP 50 DI 10.1016/bs.acr.2015.09.002 PG 20 WC Oncology SC Oncology GA BE7PC UT WOS:000375650900003 PM 26916000 ER PT S AU Calderwood, SK Neckers, L AF Calderwood, Stuart K. Neckers, Len BE Isaacs, J Whitesell, L TI Hsp90 in Cancer: Transcriptional Roles in the Nucleus SO HSP90 IN CANCER: BEYOND THE USUAL SUSPECTS SE Advances in Cancer Research LA English DT Review; Book Chapter ID HEAT-SHOCK-PROTEIN; RNA-POLYMERASE-II; GLUCOCORTICOID-RECEPTOR; GENE-EXPRESSION; P-TEFB; CHAPERONE REGULATION; BREAST-CANCER; KINASE CK2; PHOSPHORYLATION; COMPLEX AB Hsp90 plays a key role in fostering metabolic pathways essential in tumorigenesis through its functions as a molecular chaperone. Multiple oncogenic factors in the membrane and cytoplasm are thus protected from degradation and destruction. Here, we have considered Hsp90's role in transcription in the nucleus. Hsp90 functions both in regulating the activity of sequence-specific transcription factors such as nuclear receptors and HSF1, as well as impacting more globally acting factors that act on chromatin and RNA polymerase II. Hsp90 influences transcription by modulating histone modification mediated by its clients SMYD3 and trithorax/MLL, as well as by regulating the processivity of RNA polymerase II through negative elongation factor. It is not currently clear how the transcriptional role of Hsp90 may be influenced by the cancer milieu although recently discovered posttranslational modification of the chaperone may be involved. Dysregulation of Hsp90 may thus influence malignant processes both by modulating the function of specific transcription factors and effects on more globally acting general components of the transcriptional machinery. C1 [Calderwood, Stuart K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiat Oncol, Boston, MA 02215 USA. [Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Calderwood, SK (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiat Oncol, Boston, MA 02215 USA. EM scalderw@bidmc.harvard.edu FU Intramural NIH HHS; NCI NIH HHS [R0-1CA094397, R01CA119045, Z01 BC011032-01, R0-1CA047407, Z01 SC010074-12] NR 73 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X BN 978-0-12-802483-6 J9 ADV CANCER RES JI Adv.Cancer Res. PY 2016 VL 129 BP 89 EP 106 DI 10.1016/bs.acr.2015.08.002 PG 18 WC Oncology SC Oncology GA BE7PC UT WOS:000375650900005 PM 26916002 ER PT S AU Grant, P Pant, HC AF Grant, Philip Pant, Harish C. BE Omary, MB Liem, RKH TI Compartment-Specific Phosphorylation of Squid Neurofilaments SO INTERMEDIATE FILAMENT PROTEINS SE Methods in Enzymology LA English DT Review; Book Chapter ID FAST AXONAL-TRANSPORT; GIANT FIBER SYSTEM; PROTEIN-KINASE; STELLATE GANGLION; LOLIGO-PEALEI; TOPOGRAPHIC REGULATION; EXTRUDED AXOPLASM; NERVOUS-SYSTEM; TAIL DOMAIN; SYNAPSE AB Studies of the giant axon and synapse of third-order neurons in the squid stellate ganglion have provided a vast literature on neuronal physiology and axon transport. Large neuronal size also lends itself to comparative biochemical studies of cell body versus axon. These have focused on the regulation of synthesis, assembly, posttranslational modification and function of neuronal cytoskeletal proteins (microtubules (MTs) and neurofilaments (NFs)), the predominant proteins in axoplasm. These contribute to axonal organization, stability, transport, and impulse transmission responsible for rapid contractions of mantle muscles underlying jet propulsion. Studies of vertebrate NFs have established an extensive literature on NF structure, organization, and function; studies of squid NFs, however, have made it possible to compare compartment-specific regulation of NF synthesis, assembly, and function in soma versus axoplasm. Since NFs contain over 100 eligible sites for phosphorylation by protein kinases, the compartment-specific patterns of phosphorylation have been a primary focus of biochemical studies. We have learned that NF phosphorylation is tightly compartmentalized; extensive phosphorylation occurs only in the axonal compartment in squid and in vertebrate neurons. This extensive phosphorylation plays a key role in organizing NFs, in association with microtubules (MTs), into a stable, dynamic functional lattice that supports axon growth, diameter, impulse transmission, and synaptic activity. To understand how cytoskeletal phosphorylation is topographically regulated, the kinases and phosphatases, bound to NFs isolated from cell bodies and axoplasm, have also been studied. C1 [Grant, Philip; Pant, Harish C.] NINDS, CPR, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Pant, HC (reprint author), NINDS, CPR, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM panth@ninds.nih.gov NR 61 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-803491-0; 978-0-12-803470-5 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2016 VL 568 BP 615 EP 633 DI 10.1016/bs.mie.2015.09.033 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BE7QA UT WOS:000375718400023 PM 26795486 ER PT J AU Fako, V Yu, ZP Henrich, CJ Ransom, T Budhu, AS Wang, XW AF Fako, Valerie Yu, Zhipeng Henrich, Curtis J. Ransom, Tanya Budhu, Anuradha S. Wang, Xin W. TI Inhibition of wnt/beta-catenin Signaling in Hepatocellular Carcinoma by an Antipsychotic Drug Pimozide SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE Pimozide; wnt/beta-catenin; EpCAM; HCC ID DEPENDENT PROTEIN-KINASE; BETA-CATENIN; STEM-CELLS; CANCER; EPCAM; PHOSPHORYLATION; ACTIVATION; GENE; THERAPIES; LIVER AB Hepatocellular carcinoma (HCC) is one of the most common forms of malignant cancers in the world, yet very few effective systemic treatments for HCC patients exist. Thus, the development of new treatment modalities presents a great need. The wnt/beta-catenin signaling pathway is highly activated in stem cell-like aggressive HCC, which is associated with chemoresistance and poor survival in HCC patients. In a previous study, we found that an FDA-approved psychiatric drug, pimozide (PMZ), has anti-cancer properties in HCC cell lines that express epithelial cell adhesion molecule (EpCAM), a hepatic stem cell marker that is a functional down-stream target of the wnt/beta-catenin pathway. In this study, we demonstrate that PMZ effectively inhibits cell growth of HCC cells by disrupting the wnt/beta-catenin signaling pathway and reducing EpCAM expression. Thus, PMZ may be a useful molecular entity that could be repurposed as an anti-cancer therapy for treatment of HCC. C1 [Fako, Valerie; Yu, Zhipeng; Budhu, Anuradha S.; Wang, Xin W.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, 37 Convent Dr,Bldg 37,Room 3044A, Bethesda, MD 20892 USA. [Henrich, Curtis J.; Ransom, Tanya] NCI, Mol Targets Lab, Frederick, MD 21702 USA. [Henrich, Curtis J.] Leidos Biomedical Res Inc, Basic Res Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. RP Budhu, AS; Wang, XW (reprint author), NCI, 37 Convent Dr,Bldg 37,Room 3044A, Bethesda, MD 20892 USA. EM xw3u@nih.gov RI Wang, Xin/B-6162-2009 FU Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research and Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E] FX This work was supported by the Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research and Laboratory for Cancer Research, 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 US Government. NR 35 TC 1 Z9 1 U1 1 U2 1 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2016 VL 12 IS 7 BP 768 EP 775 DI 10.7150/ijbs.14718 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA DM9AR UT WOS:000376656400001 PM 27313491 ER PT J AU Sokolov, M Neumann, R AF Sokolov, Mykyta Neumann, Ronald TI Global Gene Expression Alterations as a Crucial Constituent of Human Cell Response to Low Doses of Ionizing Radiation Exposure SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Review DE human cell; ionizing radiation; low dose; gene expression; DNA microarray ID HUMAN LYMPHOBLASTOID-CELLS; HUMAN DERMAL FIBROBLASTS; EMBRYONIC STEM-CELLS; GAMMA-IRRADIATION; HUMAN SKIN; TRANSCRIPTIONAL RESPONSE; ENDOTHELIAL-CELLS; HUMAN-LYMPHOCYTES; EPITHELIAL-CELLS; TISSUE MODEL AB Exposure to ionizing radiation (IR) is inevitable to humans in real-life scenarios; the hazards of IR primarily stem from its mutagenic, carcinogenic, and cell killing ability. For many decades, extensive research has been conducted on the human cell responses to IR delivered at a low dose/low dose (LD) rate. These studies have shown that the molecular-, cellular-, and tissue-level responses are different after low doses of IR (LDIR) compared to those observed after a short-term high- dose IR exposure (HDIR). With the advent of high- throughput technologies in the late 1990s, such as DNA microarrays, changes in gene expression have also been found to be ubiquitous after LDIR. Very limited subset of genes has been shown to be consistently up-regulated by LDIR, including CDKN1A. Further research on the biological effects and mechanisms induced by IR in human cells demonstrated that the molecular and cellular processes, including transcriptional alterations, activated by LDIR are often related to protective responses and, sometimes, hormesis. Following LDIR, some distinct responses were observed, these included bystander effects, and adaptive responses. Changes in gene expression, not only at the level of mRNA, but also miRNA, have been found to crucially underlie these effects having implications for radiation protection purposes. C1 [Sokolov, Mykyta; Neumann, Ronald] NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Sokolov, M (reprint author), NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM sokolovm@mail.nih.gov; rneumann@mail.nih.gov FU Intramural Research Program at Clinical Center National Institutes of Health FX This work was supported in part by the Intramural Research Program at the Clinical Center National Institutes of Health. NR 63 TC 4 Z9 4 U1 4 U2 6 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD JAN PY 2016 VL 17 IS 1 AR 55 DI 10.3390/ijms17010055 PG 18 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA DK0DW UT WOS:000374583800053 ER PT J AU Venkatesh, P Panyutin, IV Remeeva, E Neumann, RD Panyutin, IG AF Venkatesh, Priyanka Panyutin, Irina V. Remeeva, Evgenia Neumann, Ronald D. Panyutin, Igor G. TI Effect of Chromatin Structure on the Extent and Distribution of DNA Double Strand Breaks Produced by Ionizing Radiation; Comparative Study of hESC and Differentiated Cells Lines SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE ionizing radiation; human embryonic stem cells; chromatin structure ID EMBRYONIC STEM-CELLS; HUMAN-DIPLOID FIBROBLASTS; SELF-RENEWAL; COMET ASSAY; HISTONE H3; DAMAGE; HETEROCHROMATIN; ORGANIZATION; PLURIPOTENT; REPAIR AB Chromatin structure affects the extent of DNA damage and repair. Thus, it has been shown that heterochromatin is more protective against DNA double strand breaks (DSB) formation by ionizing radiation (IR); and that DNA DSB repair may proceed differently in hetero- and euchromatin regions. Human embryonic stem cells (hESC) have a more open chromatin structure than differentiated cells. Here, we study the effect of chromatin structure in hESC on initial DSB formation and subsequent DSB repair. DSB were scored by comet assay; and DSB repair was assessed by repair foci formation via 53BP1 antibody staining. We found that in hESC, heterochromatin is confined to distinct regions, while in differentiated cells it is distributed more evenly within the nuclei. The same dose of ionizing radiation produced considerably more DSB in hESC than in differentiated derivatives, normal human fibroblasts; and one cancer cell line. At the same time, the number of DNA repair foci were not statistically different among these cells. We showed that in hESC, DNA repair foci localized almost exclusively outside the heterochromatin regions. We also noticed that exposure to ionizing radiation resulted in an increase in heterochromatin marker H3K9me3 in cancer HT1080 cells, and to a lesser extent in IMR90 normal fibroblasts, but not in hESCs. These results demonstrate the importance of chromatin conformation for DNA protection and DNA damage repair; and indicate the difference of these processes in hESC. C1 [Venkatesh, Priyanka; Panyutin, Irina V.; Remeeva, Evgenia; Neumann, Ronald D.; Panyutin, Igor G.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. RP Panyutin, IG (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM priy.venkatesh@gmail.com; ipanyutinv@mail.cc.nih.gov; remeeva@gmail.com; rneumann@mail.cc.nih.gov; ipanyuting@helix.nih.gov FU Intramural Research Program of National Institutes of Health, Clinical Center FX We thank William DeGraff for his invaluable help with cell irradiation, and Barbara Mallon and NIH Stem Cell Unit for H14 hESC line. This research was supported by the Intramural Research Program of the National Institutes of Health, Clinical Center. NR 32 TC 2 Z9 3 U1 0 U2 1 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD JAN PY 2016 VL 17 IS 1 AR 58 DI 10.3390/ijms17010058 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA DK0DW UT WOS:000374583800056 ER PT J AU Wang, YJ Hanus, JW Abu-Asab, MS Shen, DF Ogilvy, A Ou, JX Chu, XK Shi, GP Li, W Wang, SS Chan, CC AF Wang, Yujuan Hanus, Jakub W. Abu-Asab, Mones S. Shen, Defen Ogilvy, Alexander Ou, Jingxing Chu, Xi K. Shi, Guangpu Li, Wei Wang, Shusheng Chan, Chi-Chao TI NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE retina; oxidative stress; inflammation; autophagy; mitochondria ID INFLAMMASOME ACTIVATION; OXIDATIVE STRESS; CELLS; MICE; EXPRESSION; MECHANISMS; AUTOPHAGY; DISEASE; CALCIUM; IMPACT AB Inflammation and oxidative stress are involved in age-related macular degeneration (AMD) and possibly associated with an activation of neuronal apoptosis inhibitor protein/class II transcription activator of the Major Histocompatibility Complex (MHC)/heterokaryon incompatibility/telomerase-associated protein 1, leucine-rich repeat or nucleotide-binding domain, leucine-rich repeat-containing family, and pyrin domain-containing 3 (NLRP3) inflammasome. In the present study, we used a translational approach to address this hypothesis. In patients with AMD, we observed increased mRNA levels of NLRP3, pro-interleukin-1 beta (IL-1 beta) and pro-IL-18 in AMD lesions of the retinal pigment epithelium (RPE) and photoreceptor. In vitro, a similar increase was evoked by oxidative stress or lipopolysaccharide (LPS) stimulation in the adult retinal pigment epithelium (ARPE-19) cell line, and the increase was reduced in siRNA transfected cells to knockdown NLRP3. Ultrastructural studies of ARPE-19 cells showed a swelling of the cytoplasm, mitochondrial damage, and occurrence of autophagosome-like structures. NLRP3 positive dots were detected within autophagosome-like structures or in the extracellular space. Next, we used a mouse model of AMD, Ccl2/Cx3cr1 double knockout on rd8 background (DKO rd8) to ascertain the in vivo relevance. Ultrastructural studies of the RPE of these mice showed damaged mitochondria, autophagosome-like structures, and cytoplasmic vacuoles, which are reminiscent of the pathology seen in stressed ARPE-19 cells. The data suggest that the NLRP3 inflammasome may contribute in AMD pathogenesis. C1 [Wang, Yujuan; Shen, Defen; Chu, Xi K.; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Wang, Yujuan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China. [Hanus, Jakub W.; Wang, Shusheng] Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA. [Abu-Asab, Mones S.; Ogilvy, Alexander; Chan, Chi-Chao] NEI, Histopathol Core, NIH, Bethesda, MD 20892 USA. [Ou, Jingxing; Li, Wei] NEI, Unit Retinal Neurophysiol, NIH, Bethesda, MD 20892 USA. [Shi, Guangpu] NEI, Expt Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.; Chan, CC (reprint author), NEI, Histopathol Core, NIH, Bethesda, MD 20892 USA. EM yujuanwang2013@gmail.com; jhanus@tulane.edu; mones@nei.nih.gov; defen.shen@gmail.com; ogilvy.alexander@gmail.com; ouj@nei.nih.gov; xi.kathy.chu@gmail.com; shig@nei.nih.gov; liwei2@nei.nih.gov; swang1@tulane.edu; chanc@nei.nih.gov FU National Eye Institute FX The National Eye Institute Intramural Research Program provided the funding and supported the study. Nicholas Popp provided editing assistance. NR 54 TC 3 Z9 3 U1 6 U2 6 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD JAN PY 2016 VL 17 IS 1 AR 73 DI 10.3390/ijms17010073 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA DK0DW UT WOS:000374583800070 ER PT J AU Feng, HH Zhuang, P Hallett, M Zhang, YQ Li, JY Li, YJ AF Feng, Huanhuan Zhuang, Ping Hallett, Mark Zhang, Yuqing Li, Jianyu Li, Yongjie TI Characteristics of subthalamic oscillatory activity in parkinsonian akinetic-rigid type and mixed type SO INTERNATIONAL JOURNAL OF NEUROSCIENCE LA English DT Article DE Parkinson's disease; akinetic-rigid type; subthalamic nucleus; oscillatory activity; microelectrode recordings ID DEEP BRAIN-STIMULATION; HUMAN BASAL GANGLIA; BETA-OSCILLATIONS; NUCLEUS OSCILLATIONS; FUNCTIONAL-ANATOMY; MOTOR-PERFORMANCE; DISEASE; MOVEMENT; SYNCHRONIZATION; BRADYKINESIA AB Objective: To explore neurons with beta oscillatory activity in the subthalamic nucleus (STN) in relation to parkinsonian motor signs. Methods: We studied 27 patients with Parkinson's disease (PD) who underwent electrode implantation for STN deep brain stimulation. Thirteen patients were classified as akinetic-rigid (AR) type and 14 patients were classified as mixed type. Microelectrode recording was performed in the STN and the electromyogram (EMG) was simultaneously recorded. Single-unit and spectral analyses were performed. Coherence analysis was used to explore the relationship between beta oscillatory activity and EMG activity. Unpaired t-test and chi-square were used to compare the differences between the two PD types. Results: Of 130 neurons identified in the AR type, 43.8% were beta oscillatory neurons (mean: 21.3 +/- 6.87 Hz, beta FB) and 0.8% were tremor frequency oscillatory neurons (4-6 Hz, TFB). Of 102 neurons identified in the mixed type, 19.6% were beta oscillatory neurons and 26.5% were TFB oscillatory neurons. There was a significant difference in proportion of neurons with beta FB and TFB oscillations between the two PD groups. Additionally, 12% of the beta FB oscillatory neurons were coherent with limb EMG of the AR type, but there was no coherence in the mixed type. Most oscillatory neurons were localized in the dorsal portion of the STN. Conclusion: The STN beta FB oscillatory neurons correlate with parkinsonian rigidity-bradykinesia. The high proportion of beta FB oscillatory neurons found in the AR type of PD is indirect evidence for their importance in generating motor impairment. C1 [Feng, Huanhuan; Zhuang, Ping; Zhang, Yuqing; Li, Jianyu; Li, Yongjie] Capital Med Univ, Beijing Inst Funct Neurosurg, Xuanwu Hosp, Beijing, Peoples R China. [Feng, Huanhuan; Zhuang, Ping; Zhang, Yuqing; Li, Jianyu; Li, Yongjie] Beijing Inst Brain Disorders, Ctr Parkinsons Dis, Beijing, Peoples R China. [Feng, Huanhuan; Zhuang, Ping; Zhang, Yuqing; Li, Jianyu; Li, Yongjie] Capital Med Univ, Minist Educ, Key Lab Neurodegenerat Dis, Beijing, Peoples R China. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Zhuang, P (reprint author), 45 Changchun St, Beijing 100053, Peoples R China. EM zhuangp@vip.sina.com FU National Natural Science Foundation of China [81171061, 81371256, 81361128012]; Ministry of Education of Republic of China [BIBD-PXM2013-014226-07-000084]; International Alliance of Translational Neuroscience grant [PXM2014-014226-000015] FX The study was supported by National Natural Science Foundation of China [grant number 81171061], [grant number 81371256], [grant number 81361128012]; Ministry of Education of Republic of China [grant number BIBD-PXM2013-014226-07-000084; and Seed Grant of International Alliance of Translational Neuroscience [grant number PXM2014-014226-000015]. NR 40 TC 0 Z9 0 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0020-7454 EI 1563-5279 J9 INT J NEUROSCI JI Int. J. Neurosci. PY 2016 VL 126 IS 9 BP 819 EP 828 DI 10.3109/00207454.2015.1074225 PG 10 WC Neurosciences SC Neurosciences & Neurology GA DM9CC UT WOS:000376660700007 PM 26268485 ER PT J AU Wang, YH Xu, XH Pan, M Jin, T AF Wang, Youhong Xu, Xuehua Pan, Miao Jin, Tian TI ELMO1 Directly Interacts with G beta gamma Subunit to Transduce GPCR Signaling to Rac1 Activation in Chemotaxis SO JOURNAL OF CANCER LA English DT Article DE chemotaxis; G protein-coupled receptors (GPCRs); heterotrimeric G protein; small GTPase Rho; guanine nucleotide exchange factors (GEFs); ELMO/Dock complex; Rac activation ID CHEMOKINE RECEPTORS; NUCLEOTIDE EXCHANGE; CELL-MIGRATION; ACTIN NETWORK; DOCK180; COMPLEX; DOMAIN; METASTASIS; ENGULFMENT; ELEGANS AB Diverse chemokines bind to G protein-coupled receptors (GPCRs) to activate the small GTPase Rac to regulate F-actin dynamics during chemotaxis. ELMO and Dock proteins form complexes that function as guanine nucleotide exchange factors (GEFs) for Rac activation. However, the linkage between GPCR activation and the ELMO/Dock-mediated Rac activation is not fully understood. In the present study, we show that chemoattractants induce dynamic membrane translocation of ELMO1 in mammalian cells. ELMO1 plays an important role in GPCR-mediated chemotaxis. We also reveal that ELMO1 and Dock1 form a stable complex. Importantly, activation of chemokine GPCR promotes the interaction between ELMO1 and G beta gamma The ELMO1-G beta gamma interaction is through the N-terminus of ELMO1 protein and is important for the membrane translocation of ELMO1. ELMO1 is required for Rac1 activation upon chemoattractant stimulation. Our results suggest that chemokine GPCR-mediated interaction between G beta gamma and ELMO1/Dock1 complex might serve as an evolutionarily conserved mechanism for Rac activation to regulate actin cytoskeleton for chemotaxis of human cells. C1 [Wang, Youhong; Xu, Xuehua; Pan, Miao; Jin, Tian] NIAID, Chemotaxis Signaling Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Jin, T (reprint author), NIAID, Chemotaxis Signaling Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM tjin@niaid.nih.gov FU NIAID/NIH intramural funds FX This study was supported by NIAID/NIH intramural funds. We thank Dr. Bryan Fleming (NCI) for editorial assistance. NR 30 TC 2 Z9 2 U1 0 U2 0 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2016 VL 7 IS 8 BP 973 EP 983 DI 10.7150/jca.15118 PG 11 WC Oncology SC Oncology GA DM8DU UT WOS:000376591700012 PM 27313788 ER PT S AU Yoon, JH Gorospe, M AF Yoon, Je-Hyun Gorospe, Myriam BE Lin, RJ TI Identification of mRNA-Interacting Factors by MS2-TRAP (MS2-Tagged RNA Affinity Purification) SO RNA-PROTEIN COMPLEXES AND INTERACTIONS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE RBP; Ribonucleoprotein complexes; lncRNA; RNA affinity pulldown ID LONG NONCODING RNA; POSTTRANSCRIPTIONAL GENE-REGULATION; TRANSLATION; MICRORNAS; ELEMENTS; YEAST AB Posttranscriptional gene expression is governed by the interaction of mRNAs with vast families of RNA binding proteins (RBPs) and noncoding (nc)RNAs. RBPs and ncRNAs jointly influence all aspects of posttranscriptional metabolism, including pre-mRNA splicing and maturation, mRNA transport, editing, stability, and translation. Given the impact of mRNA-interacting molecules on gene expression, there is great interest in identifying mRNA-binding factors comprehensively. Here, we provide a detailed protocol to tag mRNAs with MS2 hairpins and then affinity-purify trans-binding factors (RBPs, ncRNAs) associated with the MS2-tagged mRNA. This method, termed MS2-TRAP, permits the systematic characterization of ribonucleoprotein (RNP) complexes formed on a given mRNA of interest. We describe how to prepare the mRNA-MS2 expression vector, purify the MS2-tagged RNP complexes, and detect bound RNAs and RBPs, as well as variations of this methodology to address related questions of RNP biology. C1 [Yoon, Je-Hyun; Gorospe, Myriam] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Gorospe, Myriam] NIA, Lab Genet & Genom, Intramural Res Program, NIH, Charleston, SC USA. RP Yoon, JH (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. FU Intramural NIH HHS [, ZIA AG000511-18] NR 16 TC 0 Z9 1 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3591-8; 978-1-4939-3589-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1421 BP 15 EP 22 DI 10.1007/978-1-4939-3591-8_2 D2 10.1007/978-1-4939-3591-8 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BE8HZ UT WOS:000376507200003 PM 26965253 ER PT S AU Zhang, HE AF Zhang, Hongen BE Mathe, E Davis, S TI Overview of Sequence Data Formats SO STATISTICAL GENOMICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Editorial Material; Book Chapter DE Sequencing data file format; Next-generation sequencing; Sequencing data; FASTQ; FASTA; SAM/BAM; GFF/GTF; BED; VCF ID HUMAN GENOME; RNA-SEQ; GENERATION; ALIGNMENT; PLATFORMS; ULTRAFAST; MAP AB Next-generation sequencing experiment can generate billions of short reads for each sample and processing of the raw reads will add more information. Various file formats have been introduced/developed in order to store and manipulate this information. This chapter presents an overview of the file formats including FASTQ, FASTA, SAM/BAM, GFF/GTF, BED, and VCF that are commonly used in analysis of next-generation sequencing data. C1 [Zhang, Hongen] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Zhang, HE (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 29 TC 1 Z9 1 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3578-9; 978-1-4939-3576-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1418 BP 3 EP 17 DI 10.1007/978-1-4939-3578-9_1 D2 10.1007/978-1-4939-3578-9 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BE8KT UT WOS:000376532300002 PM 27008007 ER PT S AU Mathe, E Davis, S AF Mathe, Ewy Davis, Sean BE Mathe, E Davis, S TI Statistical Genomics Methods and Protocols Preface SO STATISTICAL GENOMICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Editorial Material; Book Chapter C1 [Mathe, Ewy] Ohio State Univ, Coll Med, Biomed Informat, Columbus, OH 43210 USA. [Davis, Sean] NCI, NIH, Bethesda, MD 20892 USA. RP Mathe, E (reprint author), Ohio State Univ, Coll Med, Biomed Informat, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3578-9; 978-1-4939-3576-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1418 BP V EP V D2 10.1007/978-1-4939-3578-9 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BE8KT UT WOS:000376532300001 ER PT S AU Clough, E Barrett, T AF Clough, Emily Barrett, Tanya BE Mathe, E Davis, S TI The Gene Expression Omnibus Database SO STATISTICAL GENOMICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Microarray; High-throughput sequencing; Gene expression; Functional genomics; Database; Data mining ID NCBI GEO; BIOCONDUCTOR; MICROARRAY; GENOME; MOUSE AB The Gene Expression Omnibus (GEO) database is an international public repository that archives and freely distributes high-throughput gene expression and other functional genomics data sets. Created in 2000 as a worldwide resource for gene expression studies, GEO has evolved with rapidly changing technologies and now accepts high-throughput data for many other data applications, including those that examine genome methylation, chromatin structure, and genome-protein interactions. GEO supports community-derived reporting standards that specify provision of several critical study elements including raw data, processed data, and descriptive metadata. The database not only provides access to data for tens of thousands of studies, but also offers various Web-based tools and strategies that enable users to locate data relevant to their specific interests, as well as to visualize and analyze the data. This chapter includes detailed descriptions of methods to query and download GEO data and use the analysis and visualization tools. The GEO homepage is at http://www.ncbi.nlm.nih.gov/geo/. C1 [Clough, Emily; Barrett, Tanya] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. RP Clough, E (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 22 TC 8 Z9 8 U1 2 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3578-9; 978-1-4939-3576-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1418 BP 93 EP 110 DI 10.1007/978-1-4939-3578-9_5 D2 10.1007/978-1-4939-3578-9 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BE8KT UT WOS:000376532300006 PM 27008011 ER PT S AU Wang, ZN Jensen, MA Zenklusen, JC AF Wang, Zhining Jensen, Mark A. Zenklusen, Jean Claude BE Mathe, E Davis, S TI A Practical Guide to The Cancer Genome Atlas (TCGA) SO STATISTICAL GENOMICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE TCGA; The Cancer Genome Atlas; Cancer genomics; Next-generation sequencing; Mutation; Methylation; Proteomics; Transcriptome; Copy number; miRNA AB The Cancer Genome Atlas (TCGA) is one of the most ambitious and successful cancer genomics programs to date. The TCGA program has generated, analyzed, and made available genomic sequence, expression, methylation, and copy number variation data on over 11,000 individuals who represent over 30 different types of cancer. This chapter provides a brief overview of the TCGA program and detailed instructions and tips for investigators on how to find, access, and download this data. C1 [Wang, Zhining; Zenklusen, Jean Claude] NCI, Ctr Canc Genom, NIH, Bethesda, MD 20892 USA. [Jensen, Mark A.] Leidos Biomed Res Inc, Res Adm Directorate, Frederick Natl Lab Canc Res, Frederick, MD USA. RP Wang, ZN (reprint author), NCI, Ctr Canc Genom, NIH, Bethesda, MD 20892 USA. NR 3 TC 2 Z9 2 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3578-9; 978-1-4939-3576-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1418 BP 111 EP 141 DI 10.1007/978-1-4939-3578-9_6 D2 10.1007/978-1-4939-3578-9 PG 31 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BE8KT UT WOS:000376532300007 PM 27008012 ER PT S AU Hansen, NF AF Hansen, Nancy F. BE Mathe, E Davis, S TI Variant Calling From Next Generation Sequence Data SO STATISTICAL GENOMICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Variant detection; Next generation sequencing; Genotyping; Whole exome; Annotation ID READ ALIGNMENT; HUMAN GENOME; ULTRAFAST; FORMAT; TOOL AB The use of next generation nucleotide sequencing to discover and genotype small sequence variants has led to numerous insights into the molecular causes of various diseases. This chapter describes the use of freely available software to align next generation sequencing reads to a reference and then to use the resulting alignments to call, annotate, view, and filter small sequence variants. The suggested variant calling workflow includes read alignment with novoalign, the removal of polymerase chain reaction duplicate sequences with samtools or bamUtils, and the detection of variants with Freebayes or bam2mpg software. ANNOVAR is then used to annotate the predicted variants using gene models, population frequencies, and predicted mutation severity, producing variant files which can be viewed and filtered with the variant display tool VarSifter. C1 [Hansen, Nancy F.] NHGRI, Rockville, MD USA. RP Hansen, NF (reprint author), NHGRI, Rockville, MD USA. FU Intramural NIH HHS NR 22 TC 0 Z9 0 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3578-9; 978-1-4939-3576-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1418 BP 209 EP 224 DI 10.1007/978-1-4939-3578-9_11 D2 10.1007/978-1-4939-3578-9 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BE8KT UT WOS:000376532300012 PM 27008017 ER PT S AU Baek, S Sung, MH AF Baek, Songjoon Sung, Myong-Hee BE Mathe, E Davis, S TI Genome-Scale Analysis of Cell-Specific Regulatory Codes Using Nuclear Enzymes SO STATISTICAL GENOMICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Chromatin remodeling; DNase-seq; ATAC-seq; High-throughput sequencing; Computational genomics; Genomic footprinting ID OPEN CHROMATIN; CHIP-SEQ; DNA; ACCESSIBILITY; SEQUENCE; IDENTIFICATION; FOOTPRINTS; CIRCUITRY; DYNAMICS; ELEMENTS AB High-throughput sequencing technologies have made it possible for biologists to generate genome-wide profiles of chromatin features at the nucleotide resolution. Enzymes such as nucleases or transposes have been instrumental as a chromatin-probing agent due to their ability to target accessible chromatin for cleavage or insertion. On the scale of a few hundred base pairs, preferential action of the nuclear enzymes on accessible chromatin allows mapping of cell state-specific accessibility in vivo. Such accessible regions contain functionally important regulatory sites, including promoters and enhancers, which undergo active remodeling for cells adapting in a dynamic environment. DNase-seq and the more recent ATAC-seq are two assays that are gaining popularity. Deep sequencing of DNA libraries from these assays, termed genomic footprinting, has been proposed to enable the comprehensive construction of protein occupancy profiles over the genome at the nucleotide level. Recent studies have discovered limitations of genomic footprinting which reduce the scope of detectable proteins. In addition, the identification of putative factors that bind to the observed footprints remains challenging. Despite these caveats, the methodology still presents significant advantages over alternative techniques such as ChIP-seq or FAIRE-seq. Here we describe computational approaches and tools for analysis of chromatin accessibility and genomic footprinting. Proper experimental design and assay-specific data analysis ensure the detection sensitivity and maximize retrievable information. The enzyme-based chromatin profiling approaches represent a powerful and evolving methodology which facilitates our understanding of how the genome is regulated. C1 [Baek, Songjoon; Sung, Myong-Hee] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [Sung, Myong-Hee] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. RP Baek, S (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 AG999999, ZIA AG000390-01] NR 33 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-3578-9; 978-1-4939-3576-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2016 VL 1418 BP 225 EP 240 DI 10.1007/978-1-4939-3578-9_12 D2 10.1007/978-1-4939-3578-9 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BE8KT UT WOS:000376532300013 PM 27008018 ER PT J AU Abulseoud, OA Kasasbeh, A Min, HK Fields, JA Tye, SJ Goerss, S Knight, EJ Sampson, SM Klassen, BT Matsumoto, JY Stoppel, C Lee, KH Frye, MA AF Abulseoud, Osama A. Kasasbeh, Aimen Min, Hoon-Ki Fields, Julie A. Tye, Susannah J. Goerss, Stephan Knight, Emily J. Sampson, Shirlene M. Klassen, Bryan T. Matsumoto, Joseph Y. Stoppel, Cynthia Lee, Kendall H. Frye, Mark A. TI Stimulation-Induced Transient Nonmotor Psychiatric Symptoms following Subthalamic Deep Brain Stimulation in Patients with Parkinson's Disease: Association with Clinical Outcomes and Neuroanatomical Correlates SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Article DE Psychiatric symptoms; Subthalamic nucleus; Deep brain stimulation; Parkinson's disease ID QUALITY-OF-LIFE; NUCLEUS STIMULATION; RATING-SCALE; IMPROVEMENT; DEPRESSION; MOTOR; SURGERY; REGION; MANIA; BEHAVIOR AB Background: The clinical and neurobiological underpinnings of transient nonmotor (TNM) psychiatric symptoms during the optimization of stimulation parameters in the course of subthalamic nucleus deep brain stimulation (STN-DBS) remain under intense investigation. Methods: Forty-nine patients with refractory Parkinson's disease underwent bilateral STN-DBS implants and were enrolled in a 24-week prospective, naturalistic follow-up study. Patients who exhibited TNM psychiatric manifestations during DBS parameter optimization were evaluated for potential associations with clinical outcome measures. Results: Twenty-nine TNM+ episodes were reported by 15 patients. No differences between TNM+ and TNM- groups were found in motor outcome. However, unlike the TNM- group, TNM+ patients did not report improvement in subsyndromal depression or quality of life. TNM+ episodes were more likely to emerge during bilateral monopolar stimulation of the medial STN. Conclusions: The occurrence of TNM psychiatric symptoms during optimization of stimulation parameters was associated with the persistence of subsyndromal depression and with lower quality of life ratings at 6 months. The neurobiological underpinnings of TNM symptoms are investigated yet remain difficult to explain. (C) 2016 S. Karger AG, Basel C1 [Abulseoud, Osama A.; Fields, Julie A.; Tye, Susannah J.; Sampson, Shirlene M.; Stoppel, Cynthia; Frye, Mark A.] Mayo Clin, Dept Psychiat & Psychol, 200 First St SW, Rochester, MN 55905 USA. [Kasasbeh, Aimen; Min, Hoon-Ki; Goerss, Stephan; Knight, Emily J.; Lee, Kendall H.] Mayo Clin, Dept Neurosurg, Rochester, MN 55905 USA. [Klassen, Bryan T.; Matsumoto, Joseph Y.] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA. [Lee, Kendall H.] Mayo Clin, Dept Physiol & Biomed Engn, Rochester, MN 55905 USA. [Abulseoud, Osama A.] NIDA, IRP, Baltimore, MD USA. RP Frye, MA (reprint author), Mayo Clin, Dept Psychiat & Psychol, 200 First St SW, Rochester, MN 55905 USA.; Abulseoud, OA (reprint author), NIDA, Neuroimaging Res Branch, IRP, Biomed Res Ctr, Suite 200,Room 07A-514,251 Bayview Blvd, Baltimore, MD 21224 USA. EM osama.abulseoud@nih.gov; mfrye@mayo.edu FU NIH/NCRR CTSA KL2 [RR024151]; Mayo Foundation FX We would like to thank Ms. Veneliza Salcedo for making the illustration. This work is supported by a grant from NIH/NCRR CTSA KL2 (RR024151; to O.A.A.) and the Mayo Foundation (to M.A.F.). NR 48 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 EI 1423-0372 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2016 VL 94 IS 2 BP 93 EP 101 DI 10.1159/000445076 PG 9 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA DM7WQ UT WOS:000376571100004 PM 27093641 ER PT S AU Yang, JC Rosenberg, SA AF Yang, James C. Rosenberg, Steven A. BE Schreiber, RD TI Adoptive T-Cell Therapy for Cancer SO TUMOR IMMUNOLOGY SE Advances in Immunology LA English DT Review; Book Chapter ID TUMOR-INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; MALIGNANT-MELANOMA; AUTOLOGOUS TUMOR; IMMUNE-RESPONSE; ANTIGEN; IMMUNOTHERAPY; IDENTIFICATION; ANTIBODY; DIFFERENTIATION AB Recent developments have demonstrated that immunotherapies are capable of achieving durable antitumor responses in patients with metastatic cancer. One modality that has been able to induce durable complete regressions in patients with melanoma has been adoptive cell therapy (ACT). This has slowly been expanded to other cancer types using new approaches such as genetically engineered T-cells and other methods of antigen targeting. It now appears that immune targeting of mutated "neoantigens" plays a major role in successful ACT, as well as in other immunotherapies such as checkpoint inhibitors. This realization presents not only new challenges to ACT but also new opportunities in that all tumors now may have potential antigens to attack that can be revealed by tumor genomic sequencing. There are a variety of exciting approaches to translate these new findings into clinical trials applying ACT to the majority of cancer types. C1 [Yang, James C.; Rosenberg, Steven A.] NCI, Clin Res Ctr, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Clin Res Ctr, Bethesda, MD 20892 USA. EM sar@nih.gov NR 48 TC 7 Z9 7 U1 2 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 978-0-12-809655-0; 978-0-12-805156-6 J9 ADV IMMUNOL JI Adv.Immunol. PY 2016 VL 130 BP 279 EP 294 DI 10.1016/bs.ai.2015.12.006 PG 16 WC Oncology; Immunology SC Oncology; Immunology GA BE7PF UT WOS:000375653100008 PM 26923004 ER PT S AU Lenardo, M Lo, B Lucas, CL AF Lenardo, Michael Lo, Bernice Lucas, Carrie L. BE Littman, DR Yokoyama, WM TI Genomics of Immune Diseases and New Therapies SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 34 SE Annual Review of Immunology LA English DT Review; Book Chapter DE genomics; biochemical; mechanism; immune disorder; targeted therapy ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; CHRONIC LYMPHOCYTIC-LEUKEMIA; X-LINKED AGAMMAGLOBULINEMIA; LOSS-OF-FUNCTION; COMBINED IMMUNODEFICIENCY; INBORN-ERRORS; DELETERIOUS MUTATIONS; RHEUMATOID-ARTHRITIS; INCIDENTAL FINDINGS; PRECISION MEDICINE AB Genomic DNA sequencing technologies have been one of the great advances of the 21st century, having decreased in cost by seven orders of magnitude and opening up new fields of investigation throughout research and clinical medicine. Genomics coupled with biochemical investigation has allowed the molecular definition of a growing number of new genetic diseases that reveal new concepts of immune regulation. Also, defining the genetic pathogenesis of these diseases has led to improved diagnosis, prognosis, genetic counseling, and, most importantly, new therapies. We highlight the investigational journey from patient phenotype to treatment using the newly defined XMEN disease, caused by the genetic loss of the MAGT1 magnesium transporter, as an example. This disease illustrates how genomics yields new fundamental immunoregulatory insights as well as how research genomics is integrated into clinical immunology. At the end, we discuss two other recently described diseases, CHAI/LATAIE (CTLA-4 deficiency) and PASLI (PI3K dysregulation), as additional examples of the journey from unknown immunological diseases to new precision medicine treatments using genomics. In almost all things, what they contain of useful or applicable nature is hardly perceived unless we are deprived of them, or they become deranged in some way. William Harvey (1657) C1 [Lenardo, Michael] NIAID, Mol Dev Immune Syst Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NIAID, Clin Genom Program, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Lenardo, M (reprint author), NIAID, Mol Dev Immune Syst Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM lenardo@nih.gov OI Lo, Bernice/0000-0002-1087-6845 NR 125 TC 3 Z9 3 U1 4 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3034-7 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2016 VL 34 BP 121 EP 149 DI 10.1146/annurev-immunol-041015-055620 PG 29 WC Immunology SC Immunology GA BE7XH UT WOS:000376011300005 PM 26735698 ER PT S AU Ishizuka, IE Constantinides, MG Gudjonson, H Bendelac, A AF Ishizuka, Isabel E. Constantinides, Michael G. Gudjonson, Herman Bendelac, Albert BE Littman, DR Yokoyama, WM TI The Innate Lymphoid Cell Precursor SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 34 SE Annual Review of Immunology LA English DT Review; Book Chapter DE innate lymphoid cell development; innate lymphoid cell precursor; transcription factors; promyelocytic leukemia zinc factor ID TRANSCRIPTION FACTOR GATA3; LEUKEMIA ZINC-FINGER; NATURAL-KILLER-CELL; TISSUE INDUCER CELLS; ROR-GAMMA-T; ALLERGIC INFLAMMATION; LINEAGE COMMITMENT; FACTOR BCL11B; BONE-MARROW; DIFFERENTIATION AB The discovery of tissue-resident innate lymphoid cell populations effecting different forms of type 1, 2, and 3 immunity; tissue repair; and immune regulation has transformed our understanding of mucosal immunity and allergy. The emerging complexity of these populations along with compounding issues of redundancy and plasticity raise intriguing questions about their precise lineage relationship. Here we review advances in mapping the emergence of these lineages from early lymphoid precursors. We discuss the identification of a common innate lymphoid cell precursor characterized by transient expression of the transcription factor PLZF, and the lineage relationships of innate lymphoid cells with conventional natural killer cells and lymphoid tissue inducer cells. We also review the rapidly growing understanding of the network of transcription factors that direct the development of these lineages. C1 [Ishizuka, Isabel E.; Constantinides, Michael G.; Gudjonson, Herman; Bendelac, Albert] Univ Chicago, Comm Immunol, Chicago, IL 60637 USA. [Ishizuka, Isabel E.; Constantinides, Michael G.; Bendelac, Albert] Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA. [Gudjonson, Herman] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA. [Gudjonson, Herman] Univ Chicago, Dept Chem, 5735 S Ellis Ave, Chicago, IL 60637 USA. [Constantinides, Michael G.] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Bendelac, A (reprint author), Univ Chicago, Comm Immunol, Chicago, IL 60637 USA.; Bendelac, A (reprint author), Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM abendela@bsd.uchicago.edu OI Constantinides, Michael/0000-0003-4770-7751 FU NHLBI NIH HHS [R01 HL118092]; NIAID NIH HHS [R01 AI108643] NR 79 TC 3 Z9 3 U1 3 U2 7 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3034-7 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2016 VL 34 BP 299 EP 316 DI 10.1146/annurev-immunol-041015-055549 PG 18 WC Immunology SC Immunology GA BE7XH UT WOS:000376011300011 PM 27168240 ER PT J AU Elmariah, S Farrell, LA Daher, M Shi, X Morningstar, JE Keyes, MJ Vlahakes, GJ Inglessis, I Passeri, JJ Palacios, IF Fox, CS Rhee, EP Gerszten, RE AF Elmariah, Sammy Farrell, Laurie A. Daher, Maureen Shi, Xu Morningstar, Jordan E. Keyes, Michelle J. Vlahakes, Gus J. Inglessis, Ignacio Passeri, Jonathan J. Palacios, Igor F. Fox, Caroline S. Rhee, Eugene P. Gerszten, Robert E. TI Ketoisocaproic Acid Predicts Acute Kidney Injury and Mortality after Transcatheter Aortic Valve Replacement: A Metabolomic Profiling Study SO CARDIOLOGY LA English DT Meeting Abstract C1 [Elmariah, Sammy; Farrell, Laurie A.; Daher, Maureen; Shi, Xu; Morningstar, Jordan E.; Keyes, Michelle J.; Vlahakes, Gus J.; Inglessis, Ignacio; Passeri, Jonathan J.; Palacios, Igor F.; Rhee, Eugene P.; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2016 VL 134 IS 2 BP 194 EP 194 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL6UB UT WOS:000375773900111 ER PT B AU Rhodes, M Bushara, L AF Rhodes, Marjorie Bushara, Leslie BE Sobel, DM Jipson, JL TI LEARNING ABOUT SCIENCE AND SELF A Partnership Between the Children's Museum of Manhattan and the Psychology Department at New York University SO COGNITIVE DEVELOPMENT IN MUSEUM SETTINGS: RELATING RESEARCH AND PRACTICE LA English DT Article; Book Chapter ID ELEMENTARY-SCHOOL YEARS; SOCIAL CATEGORIES; ESSENTIALIST BELIEFS; YOUNG-CHILDREN; GENDER; ACHIEVEMENT; ACQUISITION; CONVERSATIONS; VALUES; GOALS C1 [Rhodes, Marjorie] NYU, Psychol, Dept Psychol, New York, NY 10003 USA. [Rhodes, Marjorie] NYU, Conceptual Dev & Social Cognit Lab, New York, NY 10003 USA. [Bushara, Leslie] Childrens Museum Manhattans CMOM, Educ & Guest Serv, New York, NY USA. [Bushara, Leslie] CMOM, Educ Programs, New York, NY USA. [Bushara, Leslie] CMOM, Community Partners, New York, NY USA. [Bushara, Leslie] CMOM, Natl Hlth Initiat, New York, NY USA. [Bushara, Leslie] NYC, New Hlth Educ Profess Dev Program Childcare Provi, New York, NY USA. [Bushara, Leslie] CMOM, Early Childhood Educ Curriculum, New York, NY USA. [Bushara, Leslie] NIH, Bethesda, MD USA. RP Rhodes, M (reprint author), NYU, Psychol, Dept Psychol, New York, NY 10003 USA.; Rhodes, M (reprint author), NYU, Conceptual Dev & Social Cognit Lab, New York, NY 10003 USA. NR 36 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-1-84872-489-1; 978-1-315-66755-3; 978-1-84872-488-4 PY 2016 BP 104 EP 119 PG 16 WC Art; Psychology, Educational; Psychology, Multidisciplinary SC Art; Psychology GA BE5DU UT WOS:000372625000007 ER PT J AU Fu, Y Sanchez-Cano, C Soni, R Romero-Canelon, I Hearn, JM Liu, Z Wills, M Sadler, PJ AF Fu, Ying Sanchez-Cano, Carlos Soni, Rina Romero-Canelon, Isolda Hearn, Jessica M. Liu, Zhe Wills, Martin Sadler, Peter J. TI The contrasting catalytic efficiency and cancer cell antiproliferative activity of stereoselective organoruthenium transfer hydrogenation catalysts SO DALTON TRANSACTIONS LA English DT Article ID ASYMMETRIC TRANSFER HYDROGENATION; MITOCHONDRIA-MEDIATED APOPTOSIS; CHIRAL RUTHENIUM(II) COMPLEXES; POTENTIAL ANTICANCER AGENTS; ARENE COMPLEXES; DNA-BINDING; ORGANOMETALLIC RUTHENIUM; BIDENTATE LIGANDS; OSMIUM COMPLEXES; IN-VITRO AB The rapidly growing area of catalytic ruthenium chemistry has provided new complexes with potential as organometallic anticancer agents with novel mechanisms of action. Here we report the anticancer activity of four neutral organometallic Ru-II arene N-tosyl-1,2-diphenylethane-1,2-diamine (TsDPEN) tethered transfer hydrogenation catalysts. The enantiomers (R,R)-[Ru(eta(6)-C6H5(CH2)(3)-TsDPEN-N-Me)Cl] (8) and (S,S)-[Ru(eta(6)-C6H5(CH2)(3)-TsDPEN-N-Me) Cl] (8a) exhibited higher potency than cisplatin against A2780 human ovarian cancer cells. When the N-methyl was replaced by N-H, i.e. to give (R, R)-[Ru(eta(6)-Ph(CH2)(3)-TsDPEN-NH)Cl] (7) and (S,S)-[Ru(eta(6)-Ph(CH2)(3)-TsDPEN-NH)Cl] (7a), respectively, anticancer activity decreased >5-fold. Their antiproliferative activity appears to be linked to their ability to accumulate in cells, and their mechanism of action might involve inhibition of tubulin polymerisation. This appears to be the first report of the potent anticancer activity of tethered RuII arene complexes, and the structure-activity relationship suggests that the N-methyl substituents are important for potency. In the National Cancer Institute 60-cancer-cell-line screen, complexes 8 and 8a exhibited higher activity than cisplatin towards a broad range of cancer cell lines. Intriguingly, in contrast to their potent anticancer properties, complexes 8/8a are poor catalysts for asymmetric transfer hydrogenation, whereas complexes 7/7a are effective asymmetric hydrogenation catalysts. C1 [Fu, Ying; Sanchez-Cano, Carlos; Soni, Rina; Romero-Canelon, Isolda; Liu, Zhe; Wills, Martin; Sadler, Peter J.] Univ Warwick, Dept Chem, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England. [Hearn, Jessica M.] Univ Warwick, Warwick Syst Biol Ctr, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England. [Fu, Ying] NCI, Mol Biol Lab, Ctr Canc Res, Bldg 37,Room 5011, Bethesda, MD 20892 USA. [Liu, Zhe] Qufu Normal Univ, Qingdao, Peoples R China. RP Wills, M (reprint author), Univ Warwick, Dept Chem, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England. EM p.j.sadler@warwick.ac.uk RI Sanchez-Cano, Carlos/A-3786-2017 OI Sanchez-Cano, Carlos/0000-0002-9522-0019 FU ERC (BIOINCMED) [247450]; EPSRC [EP/F034210/1]; Science City/EU ERDF/AWM; Warwick Postgraduate Research Studentships (MaXis mass spectrometer and the X-ray diffractometer); BBSRC; Warwick University FX We thank the ERC (grant no. 247450 BIOINCMED), EPSRC (grant no. EP/F034210/1) and Science City/EU ERDF/AWM (MaXis mass spectrometer and the X-ray diffractometer) for funding. Dr Michael Khan (Life Sciences) for provision of facilities for cell culture and the National Cancer Institute (NCI) for 60-cancer-cell-line screening. We also thank Warwick University for support of Rina Soni and Ying Fu through Warwick Postgraduate Research Studentships, and the BBSRC for support of Jessica Hearn (PhD studentship). NR 96 TC 3 Z9 3 U1 9 U2 20 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-9226 EI 1477-9234 J9 DALTON T JI Dalton Trans. PY 2016 VL 45 IS 20 BP 8367 EP 8378 DI 10.1039/c6dt01242f PG 12 WC Chemistry, Inorganic & Nuclear SC Chemistry GA DM1FF UT WOS:000376090100008 PM 27109147 ER PT J AU Terraneo, A Leggio, L Saladini, M Ermani, M Bonci, A Gallimberti, L AF Terraneo, Alberto Leggio, Lorenzo Saladini, Marina Ermani, Mario Bonci, Antonello Gallimberti, Luigi TI Transcranial magnetic stimulation of dorsolateral prefrontal cortex reduces cocaine use: A pilot study SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Addiction; Cocaine use disorder; Craving; Prefrontal cortex; Repeated transcranial magnetic stimulation; Optogenetics ID HUMAN MOTOR CORTEX; ANTERIOR CINGULATE CORTEX; DOPAMINE RELEASE; DRUG-ADDICTION; DEPRESSION; DEPENDENCE; EFFICACY; HYPOACTIVITY; PRAMIPEXOLE; INHIBITION AB Recent animal studies demonstrate that compulsive cocaine seeking strongly reduces prelimbic frontal cortex activity, while optogenetic stimulation of this brain area significantly inhibits compulsive cocaine seeking, providing a strong rationale for applying brain stimulation to reduce cocaine consumption. Thus, we employed repetitive transcranial magnetic stimulation (rTMS), to test if dorsolateral prefrontal cortex (DLPFC) stimulation might prevent cocaine use in humans. Thirty-two cocaine-addicted patients were randomly assigned to either the experimental group (rTMS) on the left DLPFC, or to a control group (pharmacological agents) during a 29-day study (Stage 1). This was followed by a 63-day follow-up (Stage 2), during which all participants were offered rTMS treatment. Amongst the patients who completed Stage 1, 16 were in the rTMS group (100%) and 13 in the control group (81%). No significant adverse events were noted. During Stage 1, there were a significantly higher number of cocaine-free urine drug tests in the rTMS group compared to control (p=0.004). Craving for cocaine was also significantly lower in the rTMS group compared to the controls (p=0.038). Out of 13 patients who completed Stage 1 in the control group, 10 patients received rTMS treatment during Stage 2 and showed significant improvement with favorable outcomes becoming comparable to those of the rTMS group. The present preliminary findings support the safety of rTMS in cocaine-addicted patients, and suggest its potential therapeutic role for rTMS-driven PFC stimulation in reducing cocaine use, providing a strong rationale for developing larger placebo-controlled studies. Published by Elsevier B.V. C1 [Terraneo, Alberto; Gallimberti, Luigi] IRCCS San Camillo, Venice, Italy. [Leggio, Lorenzo; Bonci, Antonello] NIDA, Intramural Res Program, Baltimore, MD USA. [Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Bethesda, MD USA. [Leggio, Lorenzo] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Saladini, Marina; Ermani, Mario] Univ Padua, Dept Neurosci, I-35100 Padua, Italy. [Bonci, Antonello] Johns Hopkins Univ, Sch Med, Solomon H Snyder Neurosci Inst, Baltimore, MD USA. [Bonci, Antonello] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. RP Bonci, A (reprint author), NIDA, Intramural Res Program, Baltimore, MD USA. EM antonello.bonci@nih.gov RI Leggio, Lorenzo/M-2972-2016 FU IRCCS San Camillo, Venice, Italy; "Novella Fronda" Foundation, Italy; Department of Neuroscience of the University of Padua, Italy; NIDA Intramural Research Program; NIAAA Division of Intramural Clinical and Biological Research FX The authors would like to acknowledge the following funding sources: IRCCS San Camillo, Venice, Italy (AT, LG), "Novella Fronda" Foundation, Italy (AT, LG), Department of Neuroscience of the University of Padua, Italy (MS, ME), NIDA Intramural Research Program (LL, AB) and NIAAA Division of Intramural Clinical and Biological Research (LL). These funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 48 TC 13 Z9 13 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD JAN PY 2016 VL 26 IS 1 BP 37 EP 44 DI 10.1016/j.euroneuro.2015.11.011 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA DM1GP UT WOS:000376093700005 PM 26655188 ER PT J AU Lorenzi, H Khan, A Behnke, MS Namasivayam, S Swapna, LS Hadjithomas, M Karamycheva, S Pinney, D Brunk, BP Ajioka, JW Ajzenberg, D Boothroyd, JC Boyle, JP Darde, ML Diaz-Miranda, MA Dubey, JP Fritz, HM Gennari, SM Gregory, BD Kim, K Saeij, JPJ Su, CL White, MW Zhu, XQ Howe, DK Rosenthal, BM Grigg, ME Parkinson, J Liu, L Kissinger, JC Roos, DS Sibley, LD AF Lorenzi, Hernan Khan, Asis Behnke, Michael S. Namasivayam, Sivaranjani Swapna, Lakshmipuram S. Hadjithomas, Michalis Karamycheva, Svetlana Pinney, Deborah Brunk, Brian P. Ajioka, James W. Ajzenberg, Daniel Boothroyd, John C. Boyle, Jon P. Darde, Marie L. Diaz-Miranda, Maria A. Dubey, Jitender P. Fritz, Heather M. Gennari, Solange M. Gregory, Brian D. Kim, Kami Saeij, Jeroen P. J. Su, Chunlei White, Michael W. Zhu, Xing-Quan Howe, Daniel K. Rosenthal, Benjamin M. Grigg, Michael E. Parkinson, John Liu, Liang Kissinger, Jessica C. Roos, David S. Sibley, L. David TI Local admixture of amplified and diversified secreted pathogenesis determinants shapes mosaic Toxoplasma gondii genomes SO NATURE COMMUNICATIONS LA English DT Article ID PLASMODIUM-FALCIPARUM; APICOMPLEXAN PARASITES; ORTHOLOG GROUPS; VIRULENCE; IDENTIFICATION; RECOMBINATION; LINEAGES; SEQUENCE; GENE; ORGANIZATION AB Toxoplasma gondii is among the most prevalent parasites worldwide, infecting many wild and domestic animals and causing zoonotic infections in humans. T. gondii differs substantially in its broad distribution from closely related parasites that typically have narrow, specialized host ranges. To elucidate the genetic basis for these differences, we compared the genomes of 62 globally distributed T. gondii isolates to several closely related coccidian parasites. Our findings reveal that tandem amplification and diversification of secretory pathogenesis determinants is the primary feature that distinguishes the closely related genomes of these biologically diverse parasites. We further show that the unusual population structure of T. gondii is characterized by clade-specific inheritance of large conserved haploblocks that are significantly enriched in tandemly clustered secretory pathogenesis determinants. The shared inheritance of these conserved haploblocks, which show a different ancestry than the genome as a whole, may thus influence transmission, host range and pathogenicity. C1 [Hadjithomas, Michalis; Karamycheva, Svetlana] J Craig Venter Inst, Dept Infect Dis, 9704 Med Ctr Dr, Rockville, MD 20850 USA. [Lorenzi, Hernan; Khan, Asis; Behnke, Michael S.; Sibley, L. David] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63130 USA. [Khan, Asis; Grigg, Michael E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Behnke, Michael S.] Louisiana State Univ, Sch Vet Med, Pathobiol Sci, Baton Rouge, LA 70803 USA. [Namasivayam, Sivaranjani] Univ Georgia, Dept Genet, Athens, GA 30602 USA. [Namasivayam, Sivaranjani; Kissinger, Jessica C.] Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30602 USA. [Swapna, Lakshmipuram S.; Parkinson, John] Hosp Sick Children, Program Mol Struct & Funct, Toronto, ON M5G 1L7, Canada. [Swapna, Lakshmipuram S.; Parkinson, John] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada. [Swapna, Lakshmipuram S.; Parkinson, John] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Pinney, Deborah; Brunk, Brian P.; Diaz-Miranda, Maria A.; Gregory, Brian D.; Roos, David S.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. [Ajioka, James W.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. [Ajzenberg, Daniel; Darde, Marie L.] Univ Limoges, Biol Resource Ctr Toxoplasma, Trop Neuroepidemiol Inst Neuroepidemiol & Trop Ne, CHU Limoges,INSERM,UMR S 1094, F-87025 Limoges, France. [Boothroyd, John C.] Stanford Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. [Boyle, Jon P.] Univ Pittsburgh, Dietrich Sch Arts & Sci, Dept Biol Sci, Pittsburgh, PA 15260 USA. [Dubey, Jitender P.; Rosenthal, Benjamin M.] ARS, Anim Parasit Dis Lab, Beltsville Agr Res Ctr, USDA, Beltsville, MD 20705 USA. [Fritz, Heather M.] Washington State Univ, Dept Vet Pathol & Microbiol, Coll Vet Med, Pullman, WA 99164 USA. [Gennari, Solange M.] Univ Sao Paulo, Fac Vet Med, Dept Prevent Vet Med & Anim Hlth, BR-05598270 Sao Paulo, Brazil. [Kim, Kami] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. [Kim, Kami] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. [Kim, Kami] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. [Saeij, Jeroen P. J.] Univ Calif, Dept Pathol Microbiol & Immunol, David, CA 95616 USA. [Su, Chunlei] Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA. [White, Michael W.] Univ S Florida, Florida Ctr Drug Discovery & Dev CDDI, Dept Mol Med, Tampa, FL 33612 USA. [White, Michael W.] Univ S Florida, Florida Ctr Drug Discovery & Dev CDDI, Dept Global Hlth, Tampa, FL 33612 USA. [Zhu, Xing-Quan] Chinese Acad Agr Sci, Lanzhou Vet Res Inst, State Key Lab Vet Etiol Biol, Key Lab Vet Parasitol Gansu Prov, Lanzhou 730046, Gansu, Peoples R China. [Howe, Daniel K.] Univ Kentucky, Dept Vet Sci, Lexington, KY 40546 USA. [Liu, Liang] Univ Georgia, Dept Stat, Athens, GA 30602 USA. [Liu, Liang; Kissinger, Jessica C.] Univ Georgia, Inst Bioinformat, Athens, GA 30602 USA. [Hadjithomas, Michalis] DOE Joint Genome Inst, Prokaryot Super Program, Walnut Creek, CA 94598 USA. RP Lorenzi, H (reprint author), Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63130 USA. EM hlorenzi@jcvi.org; sibley@wustl.edu RI Behnke, Michael/R-8839-2016; OI Behnke, Michael/0000-0002-4668-8109; Saeij, Jeroen/0000-0003-0289-7109; Diaz-Miranda, Maria Alejandra/0000-0002-6062-8049; Rosenthal, Benjamin/0000-0002-0224-3773; Kissinger, Jessica/0000-0002-6413-1101; Kim, Kami/0000-0003-3384-152X FU National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services [HHSN272200900007C]; NIH [AI059176, AI036629]; Canadian Institutes for Health Research [MOP 84556]; Intramural Research Program of NIAID at the NIH; NIAID, NIH; Department of Health and Human Services [HHSN272201400030C] FX Sequencing, assembly and annotation for the Tg and Hh genomes reported here were supported by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services under contract number HHSN272200900007C. Additional analyses were provided by community-based efforts and included support from NIH grants AI059176 and AI036629 (L.D.S.) and the Canadian Institutes for Health Research grant MOP 84556 (J.P.). Data for the Sn annotation was generously provided by M.E.G. and J.P. prior to publication and was supported by the Intramural Research Program of NIAID at the NIH (M.E.G.). Additional computing resources were provided by the SciNet HPC Consortium. We acknowledge ToxoDB (http://toxodb.org/) for providing a publically available repository for all genomic data described here and for assistance in coordinating this study. OrthoMCL and ToxoDB are supported in part with funds from the NIAID, NIH, and Department of Health and Human Services under contract HHSN272201400030C (D.S.R. & J.C.K.). NR 67 TC 12 Z9 12 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JAN PY 2016 VL 7 AR 10147 DI 10.1038/ncomms10147 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DC2AL UT WOS:000369019500002 PM 26738725 ER PT J AU Alibhai, JD Blanco, ARA Piccardo, P Caughey, B Perry, HV Freeman, TC Manson, JC AF Alibhai, James D. Blanco, Alejo R. A. Piccardo, Pedro Caughey, Byron Perry, Hugh V. Freeman, Tom C. Manson, Jean C. TI Challenging the central hypothesis that misfolded prion protein accumulation, spread and distribution predicts regions of neurodegeneration SO PRION LA English DT Meeting Abstract C1 [Alibhai, James D.; Blanco, Alejo R. A.; Piccardo, Pedro; Freeman, Tom C.; Manson, Jean C.] Univ Edinburgh, Roslin Inst, Roslin, Midlothian, Scotland. [Caughey, Byron] NIAID, Persistent Viral Dis Lab, NIH, Rocky Mt Labs, Hamilton, MT USA. [Perry, Hugh V.] Univ Southampton, Ctr Biol Sci, Southampton, Hants, England. 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 PY 2016 VL 10 SU 1 MA P-068 BP S72 EP S72 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DK1EW UT WOS:000374656300103 ER PT J AU Larimer, ME Arroyo, JA AF Larimer, Mary E. Arroyo, Judith A. TI Alcohol Use Among Special Populations SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Editorial Material C1 [Larimer, Mary E.] Univ Washington, Ctr Study Hlth & Risk Behav, Seattle, WA 98195 USA. [Larimer, Mary E.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Larimer, Mary E.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Arroyo, Judith A.] NIAAA, Bethesda, MD USA. RP Larimer, ME (reprint author), Univ Washington, Ctr Study Hlth & Risk Behav, Seattle, WA 98195 USA.; Larimer, ME (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.; Larimer, ME (reprint author), Univ Washington, Dept Psychol, Seattle, WA 98195 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 EI 1930-0573 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2016 VL 38 IS 1 BP 1 EP 3 PG 3 WC Substance Abuse SC Substance Abuse GA DL6GW UT WOS:000375738700001 PM 27295724 ER PT J AU Beedie, S Figg, WD AF Beedie, Shaunna Figg, William D. TI Resisting resistance: Establishing new treatment options for CRPC patients SO CANCER BIOLOGY & THERAPY LA English DT Article DE Delta 4-abiraterone; abiraterone; enzalutamide; prostate cancer ID PROSTATE-CANCER; STEROIDAL INHIBITORS; ABIRATERONE AB Overcoming drug resistance in castrate resistant prostate cancer requires improved understanding of mechanisms by which resistance occurs, as well as new treatment options. A recent study published in Nature (Li etal. 2015) examines the mechanism of abiraterone activity, and reveals the bioactivity of a breakdown product with exciting repercussions for therapy regimes. C1 [Beedie, Shaunna; Figg, William D.] NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 7 TC 0 Z9 0 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PY 2016 VL 17 IS 4 BP 337 EP 338 DI 10.1080/15384047.2016.1139271 PG 2 WC Oncology SC Oncology GA DL4DM UT WOS:000375583500001 PM 26828765 ER PT J AU Day, CP El Meskini, R Graff-Cherry, C Michalowski, A Ohler, ZW Van Dyke, T Merlino, G AF Day, Chi-Ping El Meskini, Rajaa Graff-Cherry, Carl Michalowski, Aleksandra Ohler, Zoe Weaver Van Dyke, Terry Merlino, Glenn TI Identifying determinants of melanoma response to immune checkpoint inhibitors via preclinical modeling SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Day, Chi-Ping; Michalowski, Aleksandra; Merlino, Glenn] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [El Meskini, Rajaa; Ohler, Zoe Weaver] Frederick Natl Lab Canc Res, Ctr Adv Preclin Res, Frederick, MD USA. [Graff-Cherry, Carl] Frederick Natl Lab Res, Lab Anim Sci Program, Frederick, MD USA. [Van Dyke, Terry] NCI, Ctr Adv Preclin Res, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2016 VL 4 IS 1 SU S MA B112 PG 1 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400205 ER PT J AU Haile, S Conner, J Mackall, C AF Haile, Samuel Conner, Joe Mackall, Crystal TI Evaluation of attenuated HSV1716 in combination with chimeric antigen receptor T cells for solid tumors SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Haile, Samuel; Mackall, Crystal] NIH, Bldg 10, Bethesda, MD 20892 USA. [Conner, Joe] Virttu Biol, Glasgow, Lanark, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2016 VL 4 IS 1 SU S MA B049 DI 10.1158/2326-6074.CRICIMTEATIAACR15-B049 PG 1 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400099 ER PT J AU Korangy, F ElGindi, M Pratt, D Venzon, D Duffy, A Makarova-Rusher, O Kerkar, S Kleiner, D Wood, B Greten, T AF Korangy, Firouzeh ElGindi, Mei Pratt, Drew Venzon, David Duffy, Austin Makarova-Rusher, Oxana Kerkar, Sid Kleiner, David Wood, Bradford Greten, Tim TI Tremelimimab activates CD4 and CD8+T cells in patients with hepatocellular carcinoma SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Korangy, Firouzeh; ElGindi, Mei; Pratt, Drew; Venzon, David; Duffy, Austin; Makarova-Rusher, Oxana; Kerkar, Sid; Kleiner, David; Wood, Bradford; Greten, Tim] NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 JAN PY 2016 VL 4 IS 1 SU S MA A195 DI 10.1158/2326-6074.CRICIMTEATIAACR15-A195 PG 1 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400303 ER PT J AU Ma, C Kesarwala, A McVicar, D Weber, A Heikenwaelder, M Greten, T AF Ma, Chi Kesarwala, Aparna McVicar, Daniel Weber, Achim Heikenwaelder, Mathias Greten, Tim TI Nonalcoholic fatty liver disease causes selective CD4+lymphocytes loss and promotes hepatocarcinogenesis SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Ma, Chi; Kesarwala, Aparna; McVicar, Daniel; Greten, Tim] NCI, Bethesda, MD 20892 USA. [Weber, Achim] Univ Zurich, Zurich, Switzerland. [Heikenwaelder, Mathias] Tech Univ Munich, D-80290 Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2016 VL 4 IS 1 SU S MA A132 DI 10.1158/2326-6074.CRICIMTEATIAACR15-A132 PG 2 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400260 ER PT J AU Maiti, S Deniger, D Dai, JL Cooper, L AF Maiti, Sourindra Deniger, Drew Dai, Jianliang Cooper, Laurence TI Transcriptional and epigenetic signatures of ex vivo propagated three distinct TCR V delta 1, TCR V delta 2 and TCR V delta 3 cell subtypes with broad specificity for malignancies SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Maiti, Sourindra; Dai, Jianliang; Cooper, Laurence] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Deniger, Drew] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2016 VL 4 IS 1 SU S MA B028 DI 10.1158/2326-6074.CRICIMTEATIAACR15-B028 PG 1 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400061 ER PT J AU Ordentlich, P Lee, MJ Tomita, Y Lee, S Tomita, S Cruickshank, S Chumsri, S Trepel, JB AF Ordentlich, Peter Lee, Min-Jung Tomita, Yusuke Lee, Sunmin Tomita, Saori Cruickshank, Scott Chumsri, Saranya Trepel, Jane B. TI Epigenetic immune modulation by entinostat in breast cancer: Correlative analysis of ENCORE 301 trial SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Ordentlich, Peter; Cruickshank, Scott] Syndax Pharmaceut Inc, Waltham, MA USA. [Lee, Min-Jung; Tomita, Yusuke; Lee, Sunmin; Tomita, Saori; Trepel, Jane B.] NCI, Bethesda, MD 20892 USA. [Chumsri, Saranya] Mayo Clin, Jacksonville, FL 32224 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 JAN PY 2016 VL 4 IS 1 SU S MA A030 DI 10.1158/2326-6074.CRICIMTEATIAACR15-A030 PG 2 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400035 ER PT J AU Prickett, TD Crystal, J Gartner, J Yao, X Pasetto, A Gros, A Lu, YC Li, YF El-Gamil, M Rosenberg, SA Robbins, P AF Prickett, Todd D. Crystal, Jessica Gartner, Jared Yao, Xin Pasetto, Anna Gros, Alena Lu, Yong-Chen Li, Yong F. El-Gamil, Mona Rosenberg, Steven A. Robbins, Paul TI Durable complete response in a patient with metastatic melanoma following adoptive transfer of autologous T cells recognizing 10 mutated tumor antigens SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Prickett, Todd D.; Crystal, Jessica; Gartner, Jared; Yao, Xin; Pasetto, Anna; Gros, Alena; Lu, Yong-Chen; Li, Yong F.; El-Gamil, Mona; Rosenberg, Steven A.; Robbins, Paul] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 JAN PY 2016 VL 4 IS 1 SU S MA PROO2 PG 1 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400221 ER PT J AU Rosenberg, S AF Rosenberg, Steven TI T cells as a drug for the personalized immunotherapy of cancer SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Rosenberg, Steven] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 JAN PY 2016 VL 4 IS 1 SU S MA IA01 PG 1 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400232 ER PT J AU Terabe, M Robertson, FC Kato, S De Ravin, E Clark, K Bloom, A Mirza, AM Berzofsky, JA AF Terabe, Masaki Robertson, Faith C. Kato, Shingo De Ravin, Emma Clark, Katharine Bloom, Anja Mirza, Amer M. Berzofsky, Jay A. TI Inhibition of TGF-betal and 2 facilitates therapeutic tumor vaccine efficacy SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Terabe, Masaki; Robertson, Faith C.; Kato, Shingo; De Ravin, Emma; Clark, Katharine; Bloom, Anja; Berzofsky, Jay A.] NCI, NIH, Bethesda, MD 20892 USA. [Mirza, Amer M.] XOMA US LLC, Berkeley, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2016 VL 4 IS 1 SU S MA B137 DI 10.1158/2326-6074.CRICIMTEATIAACR15-B137 PG 1 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400196 ER PT J AU Traver, M Campanello, L Paul, S Losert, W Shroff, H Schaefer, B AF Traver, Maria Campanello, Leonard Paul, Suman Losert, Wolfgang Shroff, Hari Schaefer, Brian TI Mechanisms of T lymphocyte activation revealed by super-resolution microscopy SO CANCER IMMUNOLOGY RESEARCH LA English DT Meeting Abstract C1 [Traver, Maria; Schaefer, Brian] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Campanello, Leonard; Losert, Wolfgang] Univ Maryland, College Pk, MD 20742 USA. [Paul, Suman] Univ Toledo, Med Ctr, 2801 W Bancroft St, Toledo, OH 43606 USA. [Shroff, Hari] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2016 VL 4 IS 1 SU S MA B046 DI 10.1158/2326-6074.CRICIMTEATIAACR15-B046 PG 1 WC Oncology; Immunology SC Oncology; Immunology GA DL2SB UT WOS:000375484400124 ER PT J AU Harvey, BK Wires, ES Trychta, KA Yan, X Richie, C Henderson, M AF Harvey, B. K. Wires, E. S. Trychta, K. A. Yan, X. Richie, C. Henderson, M. TI SERCaMP, a Secreted Reporter for Monitoring Endoplasmic Reticulum Calcium In Vitro and In Vivo SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair (ASNTR) CY APR 29-30, 2016 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Harvey, B. K.; Wires, E. S.; Trychta, K. A.; Yan, X.; Richie, C.; Henderson, M.] NIDA, Intramural Res Program, Baltimore, MD USA. [Henderson, M.] Natl Ctr Adv Translat Sci, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2016 VL 25 IS 4 BP 760 EP 760 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA DK2BB UT WOS:000374718500048 ER PT J AU Hoffer, BJ Luo, Y Hoffer, A Baratz, R Greig, NH Pick, CG AF Hoffer, B. J. Luo, Y. Hoffer, A. Baratz, R. Greig, N. H. Pick, C. G. TI Lowering Tumor Necrosis Factor-alpha Synthesis Ameliorates Neuronal and Cognitive Loss After Mild Traumatic Brain Injury in Mice SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair (ASNTR) CY APR 29-30, 2016 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Hoffer, B. J.; Luo, Y.; Hoffer, A.] Case Western Reserve Univ, Sch Med, Dept Neurosurg, Cleveland, OH USA. [Baratz, R.; Pick, C. G.] Tel Aviv Univ, Sackler Sch Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel. [Greig, N. H.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2016 VL 25 IS 4 BP 761 EP 761 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA DK2BB UT WOS:000374718500052 ER PT J AU Richie, CT Koivula, P Necarsulmer, J Baldwin, HA Fortuno, LV Zhang, Y Harvey, BK AF Richie, C. T. Koivula, P. Necarsulmer, J. Baldwin, H. A. Fortuno, L. V. Zhang, Y. Harvey, B. K. TI Development of Cre-Dependent AAV CRISPR Toolkit SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair (ASNTR) CY APR 29-30, 2016 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Richie, C. T.; Koivula, P.; Necarsulmer, J.; Baldwin, H. A.; Fortuno, L. V.; Zhang, Y.; Harvey, B. K.] NIDA, Optogenet & Transgen Technol Core, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2016 VL 25 IS 4 BP 770 EP 771 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA DK2BB UT WOS:000374718500081 ER PT J AU Yan, X Henderson, M Trychta, K Yasgar, A Jadhav, A Maloney, D Sun, H Simeonov, A Harvey, B AF Yan, X. Henderson, M. Trychta, K. Yasgar, A. Jadhav, A. Maloney, D. Sun, H. Simeonov, A. Harvey, B. TI Stabilizing Endoplasmic Calcium as a Therapeutic Target for Ischemia SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair (ASNTR) CY APR 29-30, 2016 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Yan, X.; Henderson, M.; Trychta, K.; Harvey, B.] NIDA, Intramural Res Program, Baltimore, MD USA. [Henderson, M.; Yasgar, A.; Jadhav, A.; Maloney, D.; Sun, H.; Simeonov, A.] Natl Ctr Adv Translat Sci, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2016 VL 25 IS 4 BP 777 EP 777 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA DK2BB UT WOS:000374718500100 ER PT J AU Krishnamurthy, U Szalai, G Shen, YM Xu, ZH Yadav, BK Tarca, AL Chaiworapongsa, T Hernandez-Andrade, E Than, NG Haacke, EM Romero, R Neelavalli, J AF Krishnamurthy, Uday Szalai, Gabor Shen, Yimin Xu, Zhonghui Yadav, Brijesh Kumar Tarca, Adi Laurentiu Chaiworapongsa, Tinnakorn Hernandez-Andrade, Edgar Than, Nandor Gabor Haacke, Ewart Mark Romero, Roberto Neelavalli, Jaladhar TI Longitudinal Changes in Placental Magnetic Resonance Imaging Relaxation Parameter in Murine Pregnancy: Compartmental Analysis SO GYNECOLOGIC AND OBSTETRIC INVESTIGATION LA English DT Article DE Mouse; Relaxation rate; Spin-spin relaxation; Junctional zone; Labyrinth zone; Relative contribution; High-perfusion zone; Low-perfusion zone ID UTEROPLACENTAL BLOOD-FLOW; MOUSE PLACENTA; FETOPLACENTAL VASCULATURE; GROWTH RESTRICTION; OXYGEN-SATURATION; TIME MEASUREMENTS; 1.5 T; FETAL; MRI; SUSCEPTIBILITY AB Objective: To quantify gestation-dependent longitudinal changes in the magnetic resonance transverse relaxation time (T2) parameter of the major constituent regions of the mouse placenta and to evaluate their relative contributions to changes in overall placental T2. Methods: Timed-pregnant CD-1 mice underwent magnetic resonance imaging at 7.0 T field strength, on gestational day 13 (GD13), GD15 and GD17. T2 of the placenta and its constituent high and low blood perfusion regions were quantified. A linear mixed-effects model was used to fit the T2 across gestation, and the significance of coefficients was tested. Results: A decrease in the T2 values of the placenta and its constituent regions was observed across gestation. The temporal change in T2 was estimated to be -1.85 ms/GD (p < 0.0001) for the placenta, -1.00 ms/GD (p < 0.001) for the high-perfusion zones (HPZs) and -1.66 ms/GD (p < 0.0001) for the low-perfusion zones (LPZs). Conclusion: T2 of the constituent zones of the murine placenta decreases with advancing gestation. While the T2 of the LPZ is smaller than that of the HPZ, there is no difference in their decrease rate relative to that of the whole placenta (p = 0.24). The results suggest an increased role of constituent volume fractions in affecting overall gestation-dependent placental T2 decrease in mice. (C) 2015 S. Karger AG, Basel C1 [Krishnamurthy, Uday; Shen, Yimin; Yadav, Brijesh Kumar; Haacke, Ewart Mark; Neelavalli, Jaladhar] Wayne State Univ, Sch Med, Dept Radiol, 4201 St Antoine, Detroit, MI 48201 USA. [Krishnamurthy, Uday; Yadav, Brijesh Kumar; Haacke, Ewart Mark; Neelavalli, Jaladhar] Wayne State Univ, Coll Engn, Dept Biomed Engn, Detroit, MI USA. [Szalai, Gabor; Xu, Zhonghui; Tarca, Adi Laurentiu; Chaiworapongsa, Tinnakorn; Hernandez-Andrade, Edgar; Than, Nandor Gabor; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Szalai, Gabor; Xu, Zhonghui; Tarca, Adi Laurentiu; Chaiworapongsa, Tinnakorn; Hernandez-Andrade, Edgar; Than, Nandor Gabor; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Chaiworapongsa, Tinnakorn; Hernandez-Andrade, Edgar; Than, Nandor Gabor] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Tarca, Adi Laurentiu] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Than, Nandor Gabor] Hungarian Acad Sci, Res Ctr Nat Sci, Inst Enzymol, Budapest, Hungary. RP Neelavalli, J (reprint author), Wayne State Univ, Sch Med, Dept Radiol, 4201 St Antoine, Detroit, MI 48201 USA.; Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R St, Detroit, MI 48201 USA. EM romeror@mail.nih.gov; jneelava@med.wayne.edu FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Department of Health and Human Services (DHHS); NICHD (NIH, DHHS) [HHSN275201300006C]; Small Business Technology Transfer (STTR) grant from the National Heart, Lung, and Blood Institute (NHLBI, NIH, DHHS) [1R42HL112580-01A1]; Wayne State University Perinatal Research Initiative (W.K. Kellogg Foundation) [P3018205]; Wayne State University Perinatology Virtual Discovery Grant (W.K. Kellogg Foundation) [P3018205]; Hungarian Academy of Sciences Momentum Grant [LP2014-7/2014]; Thomas C. Rumble fellowship from Wayne State University FX This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Department of Health and Human Services (DHHS) and, in part, by federal funds from NICHD (NIH, DHHS) under contract No. HHSN275201300006C. The authors are grateful to Dr. Theodore Price (Perinatology Research Branch), Dr. Lisa J. Brossia-Root, Laura Lee McIntyre and all personnel involved in the Division of Laboratory Animal Resources (Wayne State University). This research and the writing of the manuscript was also supported in part by a Small Business Technology Transfer (STTR) grant from the National Heart, Lung, and Blood Institute (NHLBI, NIH, DHHS; 1R42HL112580-01A1), by Wayne State University's Perinatal Research Initiative and Perinatology Virtual Discovery Grant to J. Neelavalli (made possible by the W.K. Kellogg Foundation award P3018205). U. Krishnamurthy was the recipient of a Thomas C. Rumble fellowship from Wayne State University. N.G. Than is the recipient of a Hungarian Academy of Sciences Momentum Grant (#LP2014-7/2014). NR 66 TC 0 Z9 0 U1 3 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-7346 EI 1423-002X J9 GYNECOL OBSTET INVES JI Gynecol.Obstet.Invest. PY 2016 VL 81 IS 3 BP 193 EP 201 DI 10.1159/000431223 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DL6SR UT WOS:000375770000001 PM 26336923 ER PT J AU Pulanic, TK Venkatesan, AM Segars, J Sokka, S Wood, BJ Stratton, P AF Pulanic, Tajana Klepac Venkatesan, Aradhana M. Segars, James Sokka, Sham Wood, Bradford J. Stratton, Pamela TI Vaginal Pessary for Uterine Repositioning during High-Intensity Focused Ultrasound Ablation of Uterine Leiomyomas SO GYNECOLOGIC AND OBSTETRIC INVESTIGATION LA English DT Article DE Vaginal pessary; Focused ultrasound; Magnetic resonance imaging; Leiomyoma ID FIBROID THERAPY; MRGFUS; EMBOLIZATION; SURGERY; WOMEN AB In order to ensure safe magnetic resonance-guided, high-intensity focused, ultrasound ablation of uterine leiomyomas, the ultrasound beam path should be free of intervening scar and bowel. Pre-treatment MRI of a 9-cm long and 7.7-cm wide leiomyomatous uterus in a 39-year-old woman with menorrhagia and abdominopelvic pain initially demonstrated a focused ultrasound treatment path without a bowel between the uterus and the abdominal wall. On the day of ablation, however, multiple loops of bowel were observed in the ultrasound beam path by MRI. Uterine repositioning was accomplished with a 76-mm donut vaginal pessary, which anteverted the fundus and successfully displaced the bowel. A vaginal pessary may aid in repositioning an axial or retroverted uterus to enable ablation of uterine leiomyomas. (C) 2015 S. Karger AG, Basel C1 [Pulanic, Tajana Klepac; Segars, James; Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Venkatesan, Aradhana M.; Wood, Bradford J.] NIH, Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. [Sokka, Sham] Philips Healthcare, Cleveland, OH USA. [Sokka, Sham] Philips Healthcare, Helsinki, Finland. RP Stratton, P (reprint author), Bldg 10,CRC,Room 1-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM ps79c@nih.gov FU National Institutes of Health (NIH) Center for Interventional Oncology; NIH Intramural Research Training Program; Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [13-CH-N054]; NIH; Philips Healthcare; National Cancer Institute [HHSN261200800001E] FX Supported in part by the National Institutes of Health (NIH) Center for Interventional Oncology, the NIH Intramural Research Training Program, the Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NICHD protocol 13-CH-N054, the NIH Clinical Center, by a Collaborative Research and Development Agreement (CRADA) between NIH and Philips Healthcare, and by the National Cancer Institute under Contract No. HHSN261200800001E. The content of this publication neither necessarily reflects the views or policies of the Department of Health and Human Services, nor does it mention trade names, names of commercial products, or organization ns imply endorsement by the US Government. ClinicalTrials.gov identifier: NCT00837161. NR 18 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-7346 EI 1423-002X J9 GYNECOL OBSTET INVES JI Gynecol.Obstet.Invest. PY 2016 VL 81 IS 3 BP 285 EP 288 DI 10.1159/000441782 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DL6SR UT WOS:000375770000016 ER PT J AU Chen, WZ Bardhi, A Feng, Y Wang, YP Qi, QQ Li, W Zhu, ZY Dyba, MA Ying, TL Jiang, SB Goldstein, H Dimitrov, DS AF Chen, Weizao Bardhi, Ariola Feng, Yang Wang, Yanping Qi, Qianqian Li, Wei Zhu, Zhongyu Dyba, Marzena A. Ying, Tianlei Jiang, Shibo Goldstein, Harris Dimitrov, Dimiter S. TI Improving the CH1-CK heterodimerization and pharmacokinetics of 4Dm2m, a novel potent CD4-antibody fusion protein against HIV-1 SO MABS LA English DT Article DE 4Dm2m; antibody; CH1-CK; fusion proteins; FcRn; HIV-1; heterodimerization; linker; pharmacokinetics; soluble CD4 ID NEONATAL FC-RECEPTOR; SINGLE HUMAN CD4; IN-VIVO ACTIVITY; HALF-LIFE; MONOCLONAL-ANTIBODIES; EXCEPTIONALLY POTENT; DOMAIN; INHIBITORS; EXPRESSION; PROTECTION AB We previously described 4Dm2m, an exceptionally potent broadly neutralizing CD4-antibody fusion protein against HIV-1. It was generated by fusing the engineered single human CD4 domain mD1.22 to both the N and C termini of the human IgG1 heavy chain constant region and the engineered single human antibody domain m36.4, which targets the CD4-induced coreceptor binding site of the viral envelope glycoprotein, to the N terminus of the human antibody kappa light chain constant region via the (G4S)3 polypeptide linkers. However, therapeutic use of 4Dm2m was limited by its short in vivo half-life. Here, we show that a combination of three approaches have successfully increased the persistence of 4Dm2m in mice. First, to stabilize the scaffold, we enhanced heterodimerization between the heavy chain constant domain 1 (CH1) and kappa light chain constant domain (CK) by using structure-guided design and phage-display library technologies. Second, to address the possibility that long polypeptide linkers might render fusion proteins more susceptible to proteolysis, we shortened the (G4S)3 linkers or replaced them with the human IgG1 hinge sequence, which is naturally designed for both flexibility and stability. Third, we introduced two amino acid mutations into the crystallizable fragment (Fc) of the scaffold previously shown to increase antibody binding to the neonatal Fc receptor (FcRn) and prolong half-lives in vivo. Collectively, these approaches markedly increased the serum concentrations of 4Dm2m in mice while not affecting other properties of the fusion protein. The new 4Dm2m variants are promising candidates for clinical development to prevent or treat HIV-1 infection. To our knowledge, this is the first report on stabilized CH1-CK, which is potentially useful as a new heterodimerization scaffold for generation of bispecific and multispecific antibodies or proteins with a more favorable pharmacokinetic profile. C1 [Chen, Weizao; Feng, Yang; Wang, Yanping; Li, Wei; Zhu, Zhongyu; Dimitrov, Dimiter S.] NCI, Prot Interact Sect, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD USA. [Bardhi, Ariola; Goldstein, Harris] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Bardhi, Ariola; Goldstein, Harris] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. [Wang, Yanping] Geneva Fdn, Tacoma, WA USA. [Qi, Qianqian; Ying, Tianlei; Jiang, Shibo] Fudan Univ, Key Lab Med Mol Virol Minist Educ & Hlth, Sch Basic Med Sci, Shanghai 200433, Peoples R China. [Qi, Qianqian; Ying, Tianlei; Jiang, Shibo] Fudan Univ, Inst Med Microbiol, Shanghai 200433, Peoples R China. [Qi, Qianqian; Jiang, Shibo] New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10021 USA. [Dyba, Marzena A.] Leidos Biomed Res Inc, Basic Sci Program, Struct Biophys Lab, Frederick Natl Lab Canc Res, Frederick, MD USA. RP Chen, WZ (reprint author), NCI, Prot Interact Sect, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD USA. EM chenw3@mail.nih.gov FU Intramural AIDS Targeted Antiviral Program (IATAP) of the National Institutes of Health (NIH); Intramural Research Program of the NIH, National Cancer Institute (NCI), Center for Cancer Research; US-China Program for Biomedical Research Cooperation; US-China Program for Research Toward a Cure for HIV/AIDS from NIH; National Nature Science Foundation of China [81361120378, 81561128006]; NIH/NIDA grants [DA033788, DA036171] FX We thank Barton F. Haynes for providing reagents. This project was supported by the Intramural AIDS Targeted Antiviral Program (IATAP) of the National Institutes of Health (NIH), the Intramural Research Program of the NIH, National Cancer Institute (NCI), Center for Cancer Research, the US-China Program for Biomedical Research Cooperation, US-China Program for Research Toward a Cure for HIV/AIDS from NIH and National Nature Science Foundation of China (#81361120378 and #81561128006), and the NIH/NIDA grants DA033788 and DA036171. NR 32 TC 3 Z9 3 U1 2 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1942-0862 EI 1942-0870 J9 MABS-AUSTIN JI mAbs PY 2016 VL 8 IS 4 BP 761 EP 774 DI 10.1080/19420862.2016.1160180 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DL7XT UT WOS:000375854400011 PM 26963639 ER PT J AU Burvenich, IJG Farrugia, W Lee, FT Catimel, B Liu, ZQ Makris, D Cao, DN O'Keefe, GJ Brechbiel, MW King, D Spirkoska, V Allan, LC Ramsland, PA Scott, AM AF Burvenich, Ingrid J. G. Farrugia, William Lee, Fook T. Catimel, Bruno Liu, Zhanqi Makris, Dahna Cao, Diana O'Keefe, Graeme J. Brechbiel, Martin W. King, Dylan Spirkoska, Violeta Allan, Laura C. Ramsland, Paul A. Scott, Andrew M. TI Cross-species analysis of Fc engineered anti-Lewis-Y human IgG1 variants in human neonatal receptor transgenic mice reveal importance of S254 and Y436 in binding human neonatal Fc receptor SO MABS LA English DT Article DE Antibody engineering; Fc receptors; molecular biology; neonatal Fc receptor; transgenic mice ID BREAST-CANCER MODEL; AMINO-ACID-RESIDUES; SERUM HALF-LIFE; MONOCLONAL-ANTIBODY; CRYSTAL-STRUCTURE; THERAPEUTIC ANTIBODIES; ENHANCED EFFICACY; SOLID TUMORS; HU3S193; RADIOIMMUNOTHERAPY AB IgG has a long half-life through engagement of its Fc region with the neonatal Fc receptor (FcRn). The FcRn binding site on IgG1 has been shown to contain I253 and H310 in the CH2 domain and H435 in the CH3 domain. Altering the half-life of IgG has been pursued with the aim to prolong or reduce the half-life of therapeutic IgGs. More recent studies have shown that IgGs bind differently to mouse and human FcRn. In this study we characterize a set of hu3S193 IgG1 variants with mutations in the FcRn binding site. A double mutation in the binding site is necessary to abrogate binding to murine FcRn, whereas a single mutation in the FcRn binding site is sufficient to no longer detect binding to human FcRn and create hu3S193 IgG1 variants with a half-life similar to previously studied hu3S193 F(ab')(2) (t(1/2 beta), I253A, 12.23h; H310A, 12.94; H435A, 12.57; F(ab')(2), 12.6h). Alanine substitutions in S254 in the CH2 domain and Y436 in the CH3 domain showed reduced binding in vitro to human FcRn and reduced elimination half-lives in huFcRn transgenic mice (t(1/2),S254A, 37.43h; Y436A, 39.53h; wild-type, 83.15h). These variants had minimal effect on half-life in BALB/c nu/nu mice (t(1/2 beta),S254A, 119.9h; Y436A, 162.1h; wild-type, 163.1h). These results provide insight into the interaction of human Fc by human FcRn, and are important for antibody-based therapeutics with optimal pharmacokinetics for payload strategies used in the clinic. C1 [Burvenich, Ingrid J. G.; Lee, Fook T.; Catimel, Bruno; Liu, Zhanqi; Makris, Dahna; Cao, Diana; King, Dylan; Spirkoska, Violeta; Allan, Laura C.; Scott, Andrew M.] Ludwig Inst Canc Res, Tumour Targeting Lab, Melbourne, Vic, Australia. [Burvenich, Ingrid J. G.; Lee, Fook T.; Catimel, Bruno; Liu, Zhanqi; Makris, Dahna; Cao, Diana; King, Dylan; Spirkoska, Violeta; Allan, Laura C.; Scott, Andrew M.] Olivia Newton John Canc Res Inst, Melbourne, Vic, Australia. [Burvenich, Ingrid J. G.; O'Keefe, Graeme J.; Scott, Andrew M.] La Trobe Univ, Sch Canc Med, Melbourne, Vic, Australia. [Farrugia, William; Ramsland, Paul A.] Burnet Inst, Biomed Res Ctr, Melbourne, Vic, Australia. [O'Keefe, Graeme J.; Scott, Andrew M.] Austin Hlth, Dept Mol Imaging & Therapy, Melbourne, Vic, Australia. [Brechbiel, Martin W.] NCI, Radioimmune Inorgan Chem Sect, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD USA. [Ramsland, Paul A.] RMIT Univ, Sch Sci, Bundoora, Vic, Australia. [Ramsland, Paul A.] Monash Univ, Dept Immunol, Melbourne, Vic 3004, Australia. [Ramsland, Paul A.] Univ Melbourne, Dept Surg, Austin Hlth, Heidelberg, Vic, Australia. [Scott, Andrew M.] Univ Melbourne, Fac Med, Melbourne, Vic, Australia. RP Scott, AM (reprint author), Ludwig Inst Canc Res, Tumour Targeting Lab, Melbourne, Vic, Australia.; Scott, AM (reprint author), Olivia Newton John Canc Res Inst, Melbourne, Vic, Australia.; Scott, AM (reprint author), La Trobe Univ, Sch Canc Med, Melbourne, Vic, Australia.; Scott, AM (reprint author), Austin Hlth, Dept Mol Imaging & Therapy, Melbourne, Vic, Australia.; Scott, AM (reprint author), Univ Melbourne, Fac Med, Melbourne, Vic, Australia. EM andrew.scott@onjcri.org.au FU Victorian Government; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; NHMRC [542512, 1030469, 487922]; Ludwig Research Institute FX This work was supported in part by Operational Infrastructure Support Program funding provided by the Victorian Government, Ludwig Research Institute and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This research was supported by NHMRC Project Grants 542512, 1030469, NHMRC Practitioner Fellowship (A.M.S), and NHMRC Program grant 487922. NR 52 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 1942-0862 EI 1942-0870 J9 MABS-AUSTIN JI mAbs PY 2016 VL 8 IS 4 BP 775 EP 786 DI 10.1080/19420862.2016.1156285 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DL7XT UT WOS:000375854400012 PM 27030023 ER PT J AU Feng, Y Wang, YP Zhu, ZY Li, W Sussman, RT Randall, M Bosse, KR Maris, JM Dimitrov, DS AF Feng, Yang Wang, Yanping Zhu, Zhongyu Li, Wei Sussman, Robyn T. Randall, Michael Bosse, Kristopher R. Maris, John M. Dimitrov, Dimiter S. TI Differential killing of CD56-expressing cells by drug-conjugated human antibodies targeting membrane-distal and membrane-proximal non-overlapping epitopes SO MABS LA English DT Article DE Antibody-drug conjugates; CD56-targeting therapy; therapeutic antibodies; neuroblastoma; PBD; CD56 internalization ID NATURAL-KILLER-CELLS; MONOCLONAL-ANTIBODY; LORVOTUZUMAB MERTANSINE; ADHESION MOLECULE; MALIGNANT GLIOMAS; LUNG-CANCER; TUMOR-CELLS; NEUROBLASTOMA; RECEPTOR; GROWTH AB CD56 (NCAM, neural cell adhesion molecule) is over-expressed in many tumor types, including neuroblastoma, multiple myeloma, small cell lung cancer, ovarian cancer, acute myeloid leukemia, NK-T lymphoma, neuroendocrine cancer and pancreatic cancer. Using phage display, we identified 2 high-affinity anti-CD56 human monoclonal antibodies (mAbs), m900 and m906, which bound to spatially separated non-overlapping epitopes with similar affinity (equilibrium dissociation constant 2.9 and 4.5nM, respectively). m900 bound to the membrane proximal fibronectin type III-like domains, whereas m906 bound to the N-terminal IgG-like domains. m906 induced significant down-regulation of CD56 in 4 neuroblastoma cell lines tested, while m900-induced downregulation of CD56 was much lower. Antibody-drug conjugates (ADCs) made by conjugation with a highly potent pyrrolobenzodiazepine dimer (PBD) exhibited killing activity that correlated with CD56 down-regulation, and to some extent with in vivo binding ability of the antibodies. The m906PBD ADC was much more potent than m900PBD, likely due to higher CD56-mediated downregulation and stronger binding to cells. Treatment with m906PBD ADC resulted in very potent cytotoxicity (IC50: 0.05-1.7 pM). These results suggest a novel approach for targeting CD56-expressing neuroblastoma cells. Further studies in animal models and in humans are needed to find whether these antibodies and their drug conjugates are promising candidate therapeutics. C1 [Feng, Yang; Wang, Yanping; Zhu, Zhongyu; Li, Wei; Dimitrov, Dimiter S.] NCI, Prot Interact Sect, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA. [Wang, Yanping] Geneva Fdn, Tacoma, WA USA. [Sussman, Robyn T.; Randall, Michael; Bosse, Kristopher R.; Maris, John M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Sussman, Robyn T.; Randall, Michael; Bosse, Kristopher R.; Maris, John M.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Bosse, Kristopher R.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Feng, Y (reprint author), NCI, Prot Interact Sect, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA. EM fengya@mail.nih.gov OI Randall, Michael/0000-0002-8687-1514 FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health; Stand Up To Cancer-St. Baldrick's Pediatric Dream Team Translational Research Grant [SU2C-AACR-DT1113] FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, and also supported by a Stand Up To Cancer-St. Baldrick's Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113). Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. NR 35 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1942-0862 EI 1942-0870 J9 MABS-AUSTIN JI mAbs PY 2016 VL 8 IS 4 BP 799 EP 810 DI 10.1080/19420862.2016.1155014 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DL7XT UT WOS:000375854400014 PM 26910291 ER PT J AU Falconi, M Eriksson, B Kaltsas, G Bartsch, DK Capdevila, J Caplin, M Kos-Kudla, B Kwekkeboom, D Rindi, G Kloppel, G Reed, N Kianmanesh, R Jensen, RT AF Falconi, M. Eriksson, B. Kaltsas, G. Bartsch, D. K. Capdevila, J. Caplin, M. Kos-Kudla, B. Kwekkeboom, D. Rindi, G. Kloeppel, G. Reed, N. Kianmanesh, R. Jensen, R. T. CA Vienna Consensus Conference TI ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors SO NEUROENDOCRINOLOGY LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-1; ZOLLINGER-ELLISON-SYNDROME; PROTON-PUMP INHIBITORS; RADIOLABELED SOMATOSTATIN ANALOG; RECEPTOR RADIONUCLIDE THERAPY; POSITRON-EMISSION-TOMOGRAPHY; CLINICAL-PRACTICE GUIDELINES; HORMONE-RELEASING-HORMONE; SINGLE-CENTER EXPERIENCE; GLUCAGON-LIKE PEPTIDE-1 C1 [Falconi, M.] Univ Vita & Salute, Hosp San Raffaele, Dept Surg, Milan, Italy. [Eriksson, B.] Univ Uppsala Hosp, Dept Endocrine Oncol, Uppsala, Sweden. [Kaltsas, G.] Natl Univ Athens, Div Endocrinol, Dept Pathophysiol, Athens, Greece. [Bartsch, D. K.] Univ Marburg, Dept Surg, Marburg, Germany. [Capdevila, J.] Vall dHebron Univ Hosp, Inst Oncol VHIO, Barcelona, Spain. [Caplin, M.] Royal Free Hosp, Neuroendocrine Tumour Unit, Pond St, London NW3 2QG, England. [Kos-Kudla, B.] Med Univ Silesia, Dept Endocrinol, Katowice, Poland. [Kwekkeboom, D.] Erasmus MC, Div Nucl Med, Dept Internal Med, Rotterdam, Netherlands. [Rindi, G.] Univ Cattolica Sacro Cuore, Policlin A Gemelli, Inst Pathol Anat, Rome, Italy. [Kloeppel, G.] Tech Univ Munich, Inst Pathol, D-80290 Munich, Germany. [Reed, N.] Gartnavel Royal Hosp, Beatson Oncol Ctr, Glasgow, Lanark, Scotland. [Kianmanesh, R.] CHU Robert Debre, Dept Surg, Reims, France. [Jensen, R. T.] NIH, Digest Dis Branch, Bldg 10, Bethesda, MD 20892 USA. RP Falconi, M (reprint author), Osped San Raffaele, Via Olgettina 60, IT-20132 Milan, Italy. EM falconi.massimo@hsr.it RI Sedlackova, Eva/B-9959-2017; OI Sedlackova, Eva/0000-0002-0089-1611; Falconi, Massimo/0000-0001-9654-7243; Niederle, Bruno/0000-0001-8107-4068; Perren, Aurel/0000-0002-6819-6092 FU Intramural NIH HHS [Z01 DK053200-17, Z99 DK999999] NR 210 TC 35 Z9 35 U1 3 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2016 VL 103 IS 2 BP 153 EP 171 DI 10.1159/000443171 PG 19 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA DJ9CK UT WOS:000374511400006 PM 26742109 ER PT J AU Abel, BS Muniyappa, R Stratton, P Skarulis, MC Gorden, P Brown, RJ AF Abel, Brent S. Muniyappa, Ranganath Stratton, Pamela Skarulis, Monica C. Gorden, Phillip Brown, Rebecca J. TI Effects of Recombinant Human Leptin (Metreleptin) on Nocturnal Luteinizing Hormone Secretion in Lipodystrophy Patients SO NEUROENDOCRINOLOGY LA English DT Article DE Leptin; Lipodystrophy; Luteinizing hormone ID PITUITARY-FUNCTION; FOLLICULAR PHASE; MENSTRUAL-CYCLE; DEFICIENCY; WOMEN; OBESITY; DYSFUNCTION; HYPOGONADISM; REPLACEMENT; MUTATION AB Background: Leptin replacement in patients with leptin gene mutations improves hypogonadotropic hypogonadism. The effects of leptin replacement on luteinizing hormone (LH) secretion in patients with lipodystrophy are unknown. Aim: We examined nocturnal LH secretory dynamics on and off exogenous leptin therapy using a 2-period, nonrandomized study that included leptin-naive and leptin-treated subjects with lipodystrophy. Methods: In period 1 (5 days) the leptin-treated group (n = 4) continued leptin; leptin was then withdrawn for the next 14 days (period 2). Leptin-naive subjects (n = 8) were studied without leptin in period 1 and with leptin replacement in period 2. LH secretory dynamics were assessed (23:00-07:00 h, sampling every 10 min, analyzed by multiparameter deconvolution algorithm) at the end of each period. Results: Mean (on vs. off: 5.0 +/- 3.1 vs. 3.2 +/- 1.3 IU/l, p = 0.04) and integrated LH concentrations (2,403 +/- 1,495 vs. 1,534 +/- 642 IU x l(-1) x min(-1), p = 0.04) were higher on leptin therapy. Leptin treatment increased burst mass (9.7 +/- 15.4 vs. 7.0 +/- 11.2 IU/l, p = 0.03) and tended to nonsignificantly increase LH burst frequency (0.77 +/- 0.26 vs.0.67 +/- 0.24 h(-1), p = 0.08). Consequently, leptin therapy increased the pulsatile production rate (64 +/- 101 vs. 57 +/- 73 IU x l(-1) x 8 h(-1), p = 0.01). On leptin, testosterone (507 +/- 286 vs. 360 +/- 174 ng/dl, p = 0.09) and estradiol levels (74 +/- 36 vs. 29 +/- 24 pg/ml, p = 0.01) were higher in males and females, respectively. Conclusions: Leptin increases spontaneous nocturnal LH secretion in patients with lipodystrophy. This is consistent with rodent and in vitro studies showing a direct stimulatory effect (hypothalamic, pituitary or both) of leptin on LH secretion. These novel findings may explicate some of the salutary effects of leptin therapy on the hypothalamic-pituitary-gonadal axis in lipodystrophy. (C) 2015 S. Karger AG, Basel C1 [Abel, Brent S.; Muniyappa, Ranganath; Skarulis, Monica C.; Gorden, Phillip; Brown, Rebecca J.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. [Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. RP Muniyappa, R (reprint author), NIDDK, Clin Endocrine Sect, Diabet Endocrinol & Obes Branch, NIH, 10 Ctr Dr MSC 1613,Bldg 10,CRC,Rm 5-3672, Bethesda, MD 20892 USA. EM muniyapr@mail.nih.gov FU intramural research programs of the NIDDK; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) FX We would like to acknowledge the patients with lipodystrophy, the clinical fellows and the nursing staff at the clinical center involved in the care of these patients, the clinical core laboratory of NIDDK, and Bristol Myers Squibb and Astra Zeneca for the metreleptin used in this study. This research was supported by the intramural research programs of the NIDDK and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). NR 24 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2016 VL 103 IS 3-4 BP 402 EP 407 DI 10.1159/000439432 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA DL6RO UT WOS:000375766500020 PM 26336809 ER PT J AU Nishisako, M Meguro, A Nomura, E Yamane, T Takeuchi, M Ota, M Kashiwagi, K Mabuchi, F Iijima, H Kawase, K Yamamoto, T Nakamura, M Negi, A Sagara, T Nishida, T Inatani, M Tanihara, H Aihara, M Araie, M Fukuchi, T Abe, H Higashide, T Sugiyama, K Kanamoto, T Kiuchi, Y Iwase, A Chin, S Ohno, S Inoko, H Mizuki, N AF Nishisako, Mami Meguro, Akira Nomura, Eiichi Yamane, Takahiro Takeuchi, Masaki Ota, Masao Kashiwagi, Kenji Mabuchi, Fumihiko Iijima, Hiroyuki Kawase, Kazuhide Yamamoto, Tetsuya Nakamura, Makoto Negi, Akira Sagara, Takeshi Nishida, Teruo Inatani, Masaru Tanihara, Hidenobu Aihara, Makoto Araie, Makoto Fukuchi, Takeo Abe, Haruki Higashide, Tomomi Sugiyama, Kazuhisa Kanamoto, Takashi Kiuchi, Yoshiaki Iwase, Aiko Chin, Shinki Ohno, Shigeaki Inoko, Hidetoshi Mizuki, Nobuhisa TI SLC1A1 Gene Variants and Normal Tension Glaucoma: An Association Study SO OPHTHALMIC GENETICS LA English DT Article DE Association study; normal tension glaucoma; polymorphism; SLC1A1 ID GENOME-WIDE ASSOCIATION; OPEN-ANGLE GLAUCOMA; OBSESSIVE-COMPULSIVE DISORDER; GLUTAMATE TRANSPORTERS; RETINA; POLYMORPHISMS; PREVALENCE; EXPRESSION; DISEASES; SNPS AB Background: It has been hypothesized that dysfunction of the solute carrier family 1, member1 gene (SLC1A1), which encodes the glutamate aspartate transporter, may play a role in normal tension glaucoma. In this study we investigate whether SLC1A1 is associated with normal tension glaucoma in Japanese patients. Methods: A total of 292 Japanese patients with normal tension glaucoma and 500 healthy control subjects were recruited. We genotyped 12 single-nucleotide polymorphisms in SLC1A1. We also performed an imputation analysis to evaluate the potential association of un-genotyped SLC1A1 single-nucleotide polymorphisms, and 165 single-nucleotide polymorphisms were imputed. Results: We observed an increased frequency of the G allele of rs10739062 in patients compared to controls (p = 0.043, OR = 1.25). The rs10739062 polymorphism exhibited a dominant effect: individuals with genotype GG and GC showed a 1.91-fold increase in risk compared to genotype CC (p = 0.0082). However, the statistical significance disappeared after Bonferroni correction for multiple testing (pc>0.05). We did not find any significant association between any of the remaining 176 single-nucleotide polymorphisms and disease risk. Conclusions: Our study showed a lack of association between SLC1A1 variants and normal tension glaucoma in Japanese patients, suggesting that the SLC1A1 gene does not play a critical role in the development of the disorder in this patient population. However, further genetic studies with larger sample sizes are needed to clarify whether SLC1A1 may make some contribution that affects the risk of developing normal tension glaucoma. C1 [Nishisako, Mami; Meguro, Akira; Nomura, Eiichi; Yamane, Takahiro; Takeuchi, Masaki; Mizuki, Nobuhisa] Yokohama City Univ, Sch Med, Dept Ophthalmol, Yokohama, Kanagawa 232, Japan. [Takeuchi, Masaki] NIH, Inflammatory Dis Sect, Natl Human Genome Res Inst, Bldg 10, Bethesda, MD 20892 USA. [Ota, Masao] Shinshu Univ, Sch Med, Dept Legal Med, Nagano, Japan. [Kashiwagi, Kenji; Mabuchi, Fumihiko; Iijima, Hiroyuki] Univ Yamanashi, Dept Ophthalmol, Fac Med, Kofu, Yamanashi, Japan. [Kawase, Kazuhide; Yamamoto, Tetsuya] Gifu Univ, Grad Sch Med, Dept Ophthalmol, Gifu, Japan. [Nakamura, Makoto; Negi, Akira] Kobe Univ, Grad Sch Med, Div Ophthalmol, Dept Surg, Kobe, Hyogo 657, Japan. [Sagara, Takeshi; Nishida, Teruo] Yamaguchi Univ, Sch Med, Dept Ophthalmol, Ube, Yamaguchi 755, Japan. [Inatani, Masaru; Tanihara, Hidenobu] Kumamoto Univ, Grad Sch Med Sci, Dept Ophthalmol & Visual Sci, Kumamoto, Japan. [Inatani, Masaru] Univ Fukui, Fac Med Sci, Dept Ophthalmol, Fukui 910, Japan. [Aihara, Makoto; Araie, Makoto] Univ Tokyo, Sch Med, Dept Ophthalmol, Tokyo 113, Japan. [Fukuchi, Takeo; Abe, Haruki] Niigata Univ, Grad Sch Med & Dent Sci, Div Ophthalmol & Visual Sci, Niigata, Japan. [Higashide, Tomomi; Sugiyama, Kazuhisa] Kanazawa Univ, Grad Sch Med Sci, Dept Ophthalmol & Visual Sci, Kanazawa, Ishikawa, Japan. [Kanamoto, Takashi; Kiuchi, Yoshiaki] Hiroshima Univ, Grad Sch Biomed Sci, Dept Ophthalmol & Visual Sci, Hiroshima, Japan. [Iwase, Aiko] Tajimi Municipal Hosp, Dept Ophthalmol, Gifu, Japan. [Chin, Shinki; Ohno, Shigeaki] Hokkaido Univ, Grad Sch Med, Dept Ophthalmol, Sapporo, Hokkaido, Japan. [Inoko, Hidetoshi] Tokai Univ, Sch Med, Div Mol Life Sci, Dept Genet Informat, Sagamihara, Kanagawa, Japan. RP Meguro, A (reprint author), Yokohama City Univ, Sch Med, Dept Ophthalmol, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. EM akmeguro@yokohama-cu.ac.jp NR 34 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 1381-6810 EI 1744-5094 J9 OPHTHALMIC GENET JI Ophthalmic Genet. PY 2016 VL 37 IS 2 BP 194 EP 200 DI 10.3109/13816810.2015.1028649 PG 7 WC Genetics & Heredity; Ophthalmology SC Genetics & Heredity; Ophthalmology GA DK2HD UT WOS:000374734400010 PM 26771863 ER PT J AU Appleby, BS O'Donnell, JK Jones, SE Cohen, ML Thompson, NR Bizzi, A Gambetti, P Safar, JG Mente, KP AF Appleby, Brian S. O'Donnell, James K. Jones, Stephen E. Cohen, Mark L. Thompson, Nicolas R. Bizzi, Alberto Gambetti, Pierluigi Safar, Jiri G. Mente, Karin P. TI Brain Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and neuropathologic correlations in human prion diseases SO PRION LA English DT Meeting Abstract C1 [Appleby, Brian S.; Cohen, Mark L.; Gambetti, Pierluigi; Safar, Jiri G.] Case Western Reserve Univ, Natl Prion Dis Pathol Surveillance Ctr, Cleveland, OH 44106 USA. [O'Donnell, James K.] Case Western Reserve Univ, Radiol, Cleveland, OH 44106 USA. [Jones, Stephen E.] Cleveland Clin, Diagnost Radiol, Cleveland, OH 44106 USA. [Thompson, Nicolas R.] Cleveland Clin, Quantitat Hlth Sci, Cleveland, OH 44106 USA. [Bizzi, Alberto] Humanitas Res Hosp IRCCS, Neuroradiol, Rozzano, Italy. [Mente, Karin P.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RI Bizzi, Alberto/K-3141-2016 OI Bizzi, Alberto/0000-0002-0253-5274 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 PY 2016 VL 10 SU 1 MA P-102 BP S86 EP S87 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DK1EW UT WOS:000374656300124 ER PT J AU Casalone, C Iulini, B Costassa, EV Corona, C Mazza, M Acutis, P Maurella, C Meloni, D Bozzetta, E Pautasso, A Capucci, L Caughey, B Puopolo, M Simmons, M Zanusso, G Pocchiari, M AF Casalone, Cristina Iulini, Barbara Costassa, Elena Vallino Corona, Cristiano Mazza, Maria Acutis, Pierluigi Maurella, Cristiana Meloni, Daniela Bozzetta, Elena Pautasso, Alessandra Capucci, Lorenzo Caughey, Byron Puopolo, Maria Simmons, Marion Zanusso, Gianluigi Pocchiari, Maurizio TI Pathogenesis and transmission of classical and atypical BSEs in cattle SO PRION LA English DT Meeting Abstract C1 [Casalone, Cristina; Iulini, Barbara; Costassa, Elena Vallino; Corona, Cristiano; Mazza, Maria; Acutis, Pierluigi; Maurella, Cristiana; Meloni, Daniela; Bozzetta, Elena; Pautasso, Alessandra] Ist Zooprofilatt Sperimentale Piemonte Liguria &, Turin, Italy. [Capucci, Lorenzo] Ist Zooprofilatt Sperimentale Lombardia & Emilia, Brescia, Italy. [Caughey, Byron] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Puopolo, Maria; Pocchiari, Maurizio] Ist Super Sanita, Viale Regina Elena 299, I-00161 Rome, Italy. [Simmons, Marion] Anim & Plant Hlth Agcy, Addlestone, Surrey, England. [Zanusso, Gianluigi] Univ Verona, I-37100 Verona, Italy. RI Bozzetta, Elena Maria/K-7580-2016; Simmons, Marion/C-2586-2011 NR 0 TC 0 Z9 0 U1 3 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 PY 2016 VL 10 SU 1 MA WS-09 BP S19 EP S20 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DK1EW UT WOS:000374656300026 ER PT J AU Favole, A Mazza, M Costassa, EV D'Angelo, A Lombardi, G Martinelli, N Avanzato, T Meloni, D Orru, C Hughson, A Acutis, P Zanusso, G Caughey, B Casalone, C Corona, C AF Favole, Alessandra Mazza, Maria Costassa, Elena Vallino D'Angelo, Antonio Lombardi, Guerino Martinelli, Nicola Avanzato, Tiziana Meloni, Daniela Orru, Christina Hughson, Andrew Acutis, Pierluigi Zanusso, Gianluigi Caughey, Byron Casalone, Cristina Corona, Cristiano TI Sensitive and rapid diagnosis of goat prion diseases by real time quaking induced conversion assay SO PRION LA English DT Meeting Abstract C1 [Favole, Alessandra; Mazza, Maria; Costassa, Elena Vallino; Avanzato, Tiziana; Meloni, Daniela; Acutis, Pierluigi; Casalone, Cristina; Corona, Cristiano] Ist Zooprofilatt Sperimentale Piemonte Liguria &, Turin, Italy. [D'Angelo, Antonio] Univ Turin, Fac Vet Med, Turin, Italy. [Lombardi, Guerino; Martinelli, Nicola] Ist Zooprofilatt Sperimentale Lombardia & Emilia, Brescia, Italy. [Orru, Christina; Hughson, Andrew; Caughey, Byron] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Zanusso, Gianluigi] Univ Verona, I-37100 Verona, Italy. 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 PY 2016 VL 10 SU 1 MA P-152 BP S117 EP S117 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DK1EW UT WOS:000374656300165 ER PT J AU Safar, JG Foutz, A Appleby, B Cohen, ML Xiao, JX Hamlin, C Cohen, Y Chen, W Blevins, J Gambetti, P Hughson, A Schonberger, LB Caughey, B AF Safar, Jiri G. Foutz, Aaron Appleby, Brian Cohen, Mark L. Xiao, Jianxin Hamlin, Clive Cohen, Yvonne Chen, Wei Blevins, Janis Gambetti, Pierluigi Hughson, Andrew Schonberger, Lawrence B. Caughey, Byron TI Autopsy validation of second generation RT QuIC for diagnosis and differentiation of human prion diseases: Results from the US National Prion Disease Pathology Surveillance Center SO PRION LA English DT Meeting Abstract C1 [Safar, Jiri G.; Foutz, Aaron; Appleby, Brian; Cohen, Mark L.; Xiao, Jianxin; Hamlin, Clive; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Gambetti, Pierluigi] Case Western Reserve Univ, Natl Prion Dis Pathol Surveillance Ctr, Cleveland, OH 44106 USA. [Hughson, Andrew; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. [Schonberger, Lawrence B.] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 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 PY 2016 VL 10 SU 1 MA O-13 BP S30 EP S30 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DK1EW UT WOS:000374656300039 ER PT J AU Voisset, CP Blondel, M Soubigou, F Evrard, J Nguyen, PH Hassin, N Chedin, S Gillet, R Contesse, MA Friocourt, G Stahl, G Jones, G AF Voisset, Cecile P. Blondel, Marc Soubigou, Flavie Evrard, Justine Phu Hai Nguyen Hassin, Naushaba Chedin, Stephane Gillet, Reynald Contesse, Marie-Astrid Friocourt, Gaelle Stahl, Guillaume Jones, Gary TI Protein folding activity of the ribosome: Key player in yeast prion propagation SO PRION LA English DT Meeting Abstract C1 [Voisset, Cecile P.; Blondel, Marc; Soubigou, Flavie; Evrard, Justine; Phu Hai Nguyen; Contesse, Marie-Astrid; Friocourt, Gaelle] Univ Medecine Brest, Etab Francais Sang EFS Bretagne, CHRU Brest, Inserm,UMR 1078,Morvan Hosp,Mol Genet Lab, Brest, France. [Hassin, Naushaba; Jones, Gary] Maynooth Univ, Yeast Genet Lab, Dept Biol, Maynooth, Kildare, Ireland. [Chedin, Stephane] Univ Paris 11, I2BC, CEA Saclay, UMR 9198,CEA,CNRS,SBIGeM, Gif Sur Yvette, France. [Gillet, Reynald] Univ Rennes 1, CNRS, UMR 6290, IGDR,Translat & Folding Team, Rennes, France. [Stahl, Guillaume] Univ Toulouse, Lab Biol Mol Eucaryotes, CNRS, Toulouse, France. [Phu Hai Nguyen] NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, NIH,Rocky Mt Labs, Hamilton, MT USA. [Hassin, Naushaba] NICHHD, Sect Format RNA, NIH, Bethesda, MD 20892 USA. NR 12 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 PY 2016 VL 10 SU 1 MA O-04 BP S24 EP S25 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DK1EW UT WOS:000374656300031 ER PT J AU Zanusso, G Bongianni, M Orru, CD Groveman, BR Sacchetto, L Fiorini, M Tonoli, G Triva, G Capaldi, S Hughson, AH Ladogana, A Poleggi, A Monaco, S Pocchiari, M Caughey, B AF Zanusso, Gianluigi Bongianni, Matilde Orru, Christina D. Groveman, Bradley R. Sacchetto, Luca Fiorini, Michele Tonoli, Giovanni Triva, Giorgio Capaldi, Stefano Hughson, Andrew H. Ladogana, Anna Poleggi, Anna Monaco, Salvatore Pocchiari, Maurizio Caughey, Byron TI Accuracy of Creutzfeldt-Jakob disease diagnosis using RT-QuIC testing of olfactory mucosa and cerebrospinal fluid samples SO PRION LA English DT Meeting Abstract C1 [Zanusso, Gianluigi; Bongianni, Matilde; Fiorini, Michele; Monaco, Salvatore] Univ Verona, Dept Neurosci Biomed & Motor Sci, I-37100 Verona, Italy. [Orru, Christina D.; Groveman, Bradley R.; Hughson, Andrew H.; Caughey, Byron] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. [Sacchetto, Luca] Azienda Osped Univ Integrata, Clin Otorinolaringoiatr, Verona, Italy. [Tonoli, Giovanni] SOC Otorinolaringoiatria, Rovigo, Italy. [Triva, Giorgio] Copan Italia Spa, Via Perotti 10, Brescia, Italy. [Capaldi, Stefano] Univ Verona, Dept Biotechnol, Biocrystallog Lab, I-37100 Verona, Italy. [Ladogana, Anna; Poleggi, Anna; Pocchiari, Maurizio] Ist Super Sanita, Dept Cell Biol & Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy. RI Ladogana, Anna/K-1415-2016 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 PY 2016 VL 10 SU 1 MA P-115 BP S94 EP S95 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DK1EW UT WOS:000374656300135 ER PT J AU Zou, WQ Yuan, J Cooperman, L Orru, C Appleby, BS Rarick, J Wyza, RE Fujioka, H Zhang, SL Quinones-Mateu, ME Caughey, B Tesar, P AF Zou, Wenquan Yuan, Jue Cooperman, Leslie Orru, Christina Appleby, Brian S. Rarick, Jason Wyza, Robert E. Fujioka, Hisashi Zhang, Shulin Quinones-Mateu, Miguel E. Caughey, Byron Tesar, Paul TI Cellular phenotypes of prion disease in skin-derived fibroblasts of asymptomatic PrP mutation carriers and sporadic CJD patients SO PRION LA English DT Meeting Abstract C1 [Zou, Wenquan; Yuan, Jue; Cooperman, Leslie; Appleby, Brian S.; Rarick, Jason; Wyza, Robert E.; Fujioka, Hisashi; Zhang, Shulin; Quinones-Mateu, Miguel E.; Tesar, Paul] Case Western Reserve Univ, Pathol, Cleveland, OH 44106 USA. [Orru, Christina; Caughey, Byron] NIAID, 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 PY 2016 VL 10 SU 1 MA P-040 BP S57 EP S57 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DK1EW UT WOS:000374656300080 ER PT J AU Zou, WQ Orru, CD Yuan, J Appleby, BS Li, Y Rarick, J Kong, QZ Cohen, ML Zhang, SL Groveman, BR Safar, JG Quinones-Mateu, ME Caughey, B AF Zou, Wenquan Orru, Christina D. Yuan, Jue Appleby, Brian S. Li, Yu Rarick, Jason Kong, Qingzhong Cohen, Mark L. Zhang, Shulin Groveman, Bradley R. Safar, Jiri G. Quinones-Mateu, Miguel E. Caughey, Byron TI PrPSc in the skin of CJD patients SO PRION LA English DT Meeting Abstract C1 [Zou, Wenquan; Yuan, Jue; Appleby, Brian S.; Li, Yu; Rarick, Jason; Kong, Qingzhong; Cohen, Mark L.; Zhang, Shulin; Safar, Jiri G.; Quinones-Mateu, Miguel E.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Orru, Christina D.; Groveman, Bradley R.; Caughey, Byron] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 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 PY 2016 VL 10 SU 1 MA O-12 BP S29 EP S29 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DK1EW UT WOS:000374656300038 ER PT J AU Omura, Y Lu, D Jones, MK Nihrane, A Duvvi, H Yapor, D Shimotsuura, Y Ohki, M AF Omura, Yoshiaki Lu, Dominic Jones, Marilyn K. Nihrane, Abdallah Duvvi, Harsha Yapor, Dario Shimotsuura, Yasuhiro Ohki, Motomu TI Optimal Dose of Vitamin D-3 400 IU for Average Adults has A Significant Anti-Cancer Effect, While Widely Used 2000 IU or Higher Promotes Cancer: Marked Reduction of Taurine & 1 alpha, 25(OH)(2)D-3 Was Found In Various Cancer Tissues and Oral Intake of Optimal Dose of Taurine 175mg for Average Adults, Rather Than 500mg, Was Found to Be A New Potentially Safe and More Effective Method of Cancer Treatment SO ACUPUNCTURE & ELECTRO-THERAPEUTICS RESEARCH LA English DT Article DE Taurine; Vitamin D-3; cholesterol; 1 alpha, 25(OH)(2)Vitamin D-3(=1 alpha, 25(OH)(2)D-3); Oncogene C-fosAb2; Integrin alpha(5)beta(1); 8-OH-dG; HPV-16; CMV; Zika Virus; Acetylcholine; ANP (Atrial Natriuretic Peptide); DHEA; Cilantro; omega 3 fish oil ID BREAST-CANCER; ASBESTOS; CHRYSOTILE; DIAGNOSIS; DHEA; ETC. AB During the past 10 years, the author had found that the optimal dose of Vitamin D-3 400 I.U. has safe & effective anticancer effects, while commonly used 2000 similar to 5000 I.U. of Vit. D-3 often creates a 2 similar to 3 time increase in cancer markers. We examined the concentration of Taurine in normal internal organs and in cancer using Bi-Digital O-Ring Test. We found that Taurine levels in normal tissue are 4 similar to 6ng. But, the amount of Taurine of average normal value of 5.0 similar to 5.25ng was strikingly reduced to 0.0025 similar to 0.0028ng in this study of several examples in adenocarcinomas of the esophagus, stomach, pancreas, colon, prostate, and lung, as well as breast cancer. The lowest Taurine levels of 0.0002 similar to 0.0005ng were found in so called Zika virus infected babies from Brazil with microcephaly. While Vitamin D-3 receptor stimulant 1 alpha, 25 (OH)(2)D-3 in normal tissues was 0.45 similar to 0.53ng, they were reduced to 0.0025 similar to 0.006ng in cancers (1/100th similar to 1/200th of normal value), particularly in various adenocarcinomas. All of these adenocarcinomas had about 1500ng HPV-16 viral infection. In 500 breast cancers, about 97% had HPV-16. The optimal dose of Taurine for average adult has been found to be about 175mg, rather than the widely used 500mg. In addition, since Taurine is markedly reduced to close to 1/1000th similar to 1/2000th of its normal value in these cancer tissues, we examined the effect of the optimal dose of Taurine on cancer patients. Optimal dose of Taurine produced a very significant decrease in cancer-associated parameters, such as Oncogene C-fosAb2 & Integrin alpha(5)beta(1) being reduced to less than 1/1,000th, and 8-OH-dG (which increases in the presence of DNA mutation) reduced to less than 1/10th. The optimal dose of Taurine 175mg for average adult various cancer patient 3 times a day alone provide beneficial effects with very significant anti-cancer effects with strikingly increased urinary excretion of bacteria, viruses, & funguses, asbestos, toxic metals & other toxic substances. However, optimal doses of Taurine combined with optimal individualized doses of omega 3 fish oil [EPA 180mg & DHA 120mg] & special cilantro tablet 3 times/day without creating harmful drug interactions among them including other essential drugs, is often extremely safe, more effective, economical & non-invasive new treatment for various cancer patients. C1 [Omura, Yoshiaki] New York Med Coll, Dept Family & Community Med, Valhalla, NY 10595 USA. [Omura, Yoshiaki] Heart Dis Res Fdn, Med Res, Brooklyn, NY USA. [Omura, Yoshiaki] Int Coll Acupuncture & Electrotherapeut, New York, NY USA. [Lu, Dominic] Univ Penn, Oral Med, Philadelphia, PA 19104 USA. [Lu, Dominic] Amer Soc Advancement Anesthesia & Sedat Dent, Chicago, IL USA. [Lu, Dominic; Jones, Marilyn K.; Yapor, Dario] Int Coll Acupuncture & Electrotherapeut, Holist Dent, New York, NY USA. [Jones, Marilyn K.] Holist Dent Ctr Houston, Houston, TX USA. [Jones, Marilyn K.] Univ Houston, Chem, Houston, TX 77004 USA. [Nihrane, Abdallah; Duvvi, Harsha; Shimotsuura, Yasuhiro] Int Coll Acupuncture & Electrotherapeut, Integrat Med, New York, NY USA. [Nihrane, Abdallah] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Nihrane, Abdallah] NIH, Bldg 10, Bethesda, MD 20892 USA. [Duvvi, Harsha] New York Med Coll, Dept Family & Community Med & Neurologist, Valhalla, NY 10595 USA. [Shimotsuura, Yasuhiro] Japan Bidigital O Ring Test Assoc, Tokyo, Japan. [Shimotsuura, Yasuhiro; Ohki, Motomu] ORT Life Sci Res Inst, Kurume, Fukuoka, Japan. RP Omura, Y (reprint author), 800 Riverside Dr 8-I, New York, NY 10032 USA. EM icaet@yahoo.com NR 26 TC 2 Z9 2 U1 1 U2 5 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0360-1293 EI 2167-9010 J9 ACUPUNCTURE ELECTRO JI Acupunct. Electro-Ther. Res. PY 2016 VL 41 IS 1 BP 39 EP 60 DI 10.3727/036012916X14597946741564 PG 22 WC Integrative & Complementary Medicine; Neurosciences SC Integrative & Complementary Medicine; Neurosciences & Neurology GA DK3PX UT WOS:000374830700003 PM 27244952 ER PT S AU Wickner, RB Edskes, HK Gorkovskiy, A Bezsonov, EE Stroobant, EE AF Wickner, R. B. Edskes, H. K. Gorkovskiy, A. Bezsonov, E. E. Stroobant, E. E. BE Friedmann, T Dunlap, JC Goodwin, SF TI Yeast and Fungal Prions: Amyloid-Handling Systems, Amyloid Structure, and Prion Biology SO ADVANCES IN GENETICS, VOL 93 SE Advances in Genetics LA English DT Review; Book Chapter ID HET-S PRION; BETA-SHEET STRUCTURE; TRANSMISSION ELECTRON-MICROSCOPY; SACCHAROMYCES-CEREVISIAE PSI+; RIBOSOME-ASSOCIATED COMPLEX; PROTEIN-QUALITY CONTROL; TERMINATION FACTOR ERF3; 2-MU-M CIRCLE PLASMID; FULL-LENGTH PROTEIN; SOLID-STATE NMR AB Yeast prions (infectious proteins) were discovered by their outre genetic properties and have become important models for an array of human prion and amyloid diseases. A single prion protein can become any of many distinct amyloid forms (called prion variants or strains), each of which is self-propagating, but with different biological properties (eg, lethal vs mild). The folded in-register parallel beta sheet architecture of the yeast prion amyloids naturally suggests a mechanism by which prion variant information can be faithfully transmitted for many generations. The yeast prions rely on cellular chaperones for their propagation, but can be cured by various chaperone imbalances. The Btn2/Cur1 system normally cures most variants of the [URE3] prion that arise. Although most variants of the [PSI+] and [URE3] prions are toxic or lethal, some are mild in their effects. Even the most mild forms of these prions are rare in the wild, indicating that they too are detrimental to yeast. The beneficial [Het-s] prion of Podospora anserina poses an important contrast in its structure, biology, and evolution to the yeast prions characterized thus far. C1 [Wickner, R. B.; Edskes, H. K.; Gorkovskiy, A.; Bezsonov, E. E.; Stroobant, E. E.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov RI Gorkovskiy, Anton/J-8930-2016 OI Gorkovskiy, Anton/0000-0003-4811-2282 FU Intramural NIH HHS NR 217 TC 6 Z9 6 U1 5 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2660 BN 978-0-12-805217-4; 978-0-12-804801-6 J9 ADV GENET JI Adv. Genet. PY 2016 VL 93 BP 191 EP 236 DI 10.1016/bs.adgen.2015.12.003 PG 46 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA BE7NZ UT WOS:000375606200004 PM 26915272 ER PT J AU Forbes, LR Milner, J Haddad, E AF Forbes, Lisa R. Milner, Josh Haddad, Elie TI Signal transducer and activator of transcription 3: a year in review SO CURRENT OPINION IN HEMATOLOGY LA English DT Review DE autoimmunity; immunodeficiency; Job's syndrome; lymphoproliferation; signal transducer and activator of transcription 3; Th17 cells ID HYPER-IGE SYNDROME; CD8(+) T-CELLS; STAT3 MUTATIONS; B-CELLS; DISEASE; IMMUNITY; MEMORY; PHOSPHORYLATION; DIFFERENTIATION; MYCOBACTERIUM AB Purpose of review Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor involved in a wide variety of cellular functions. Germline loss-of-function mutations are known to cause hyper-IgE immunodeficiency (autosomal dominant hyper IgE syndrome),.whereas somatic gain-of-function mutations have been described in large granular cell leukemia, and polymorphisms in STAT3 have been associated with inflammatory bowel disease and other solid organ tumors. The review examines recent discoveries in our understanding of the nonmalignant disease processes affected by STAT3 mutations in human disease. Recent findings Germline STAT3 gain-of-function mutations have recently been identified in patients with an early-onset autoimmunity/lymphoproliferative syndrome. STAT3 plays a previously unrecognized role in several facets of the pathogenesis of allergy. Loss-of-function STAT3 mutations revealed critical roles for STAT3 in the development and function of several lymphocyte populations and in their role in host defense. Summary The discovery of new gain-of-function mutations in STAT3, as well as new studies among patients with loss of-function mutations, expand the understanding of the pathophysiology of STAT3 function and its importance in regulating the immune system. These findings contribute to elucidating STAT3 biology and clinical symptoms in patients with the different disease phenotypes. C1 [Forbes, Lisa R.] Texas Childrens Hosp, Baylor Coll Med, Ctr Human Immunobiol, Sect Immunol,Dept Pediat Allergy & Rheumatol, Houston, TX 77030 USA. [Milner, Josh] NIAID, Natl Inst Hlth Genet & Pathogenesis Allergy Sect, Lab Allerg Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Haddad, Elie] Univ Montreal, Dept Pediat, CHU St Justine, Res Ctr, Montreal, PQ H3C 3J7, Canada. [Haddad, Elie] Univ Montreal, Dept Microbiol Immunol & Infectiol, CHU St Justine, Res Ctr, Montreal, PQ, Canada. RP Haddad, E (reprint author), Ctr Hosp Univ St Justine, Montreal, PQ, Canada. EM elie.haddad@umontreal.ca FU Department of Pediatrics, Section of Immunology Allergy and Rheumatology, Baylor College of Medicine FX This work was supported Department of Pediatrics, Section of Immunology Allergy and Rheumatology, Baylor College of Medicine and by the intramural research program, NIAID, NIH. NR 42 TC 0 Z9 0 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1065-6251 EI 1531-7048 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JAN PY 2016 VL 23 IS 1 BP 23 EP 27 DI 10.1097/MOH.0000000000000206 PG 5 WC Hematology SC Hematology GA DL2UK UT WOS:000375490500005 PM 26574998 ER PT J AU Liu, BY Lu, XW Ruan, H Cui, JW Li, HG AF Liu, Baoyong Lu, Xiaowei Ruan, Hong Cui, Jiwei Li, Hongguang TI Synthesis and Applications of Glyconanoparticles SO CURRENT ORGANIC CHEMISTRY LA English DT Article DE Glyconanoparticles; methodologies; carbohydrate-lectin interactions; biomedicine ID FUNCTIONALIZED GOLD NANOPARTICLES; MESOPOROUS SILICA NANOPARTICLES; IRON-OXIDE NANOPARTICLES; CAPPED QUANTUM DOTS; IN-VITRO; MAGNETIC NANOPARTICLES; DRUG-DELIVERY; SILVER GLYCONANOPARTICLES; CARBOHYDRATE INTERACTIONS; BIOMEDICAL APPLICATIONS AB Glyconanoparticles are the subject of numerous literatures and are emerging for applications in biomedicine, glycoscience, and material science due to their unique properties. They are hybrid materials each of which contains a nanoparticle core surrounded by a carbohydrate shell. The core can be metallic, magnetic, and/or photoluminescent, while the shell may be composed of mono-, di-, oligo- and/or poly-saccharides. Sugars are attached to the surface of the nanoparticles through covalent or non-covalent interaction. Here, we give a brief summary of the synthetic methodologies adopted in the preparation of different types of glyconanoparticles, which can be utilized in various applications including catalysis, drug delivery, vaccine, imaging and study of carbohydrate-lectin interactions. C1 [Liu, Baoyong; Ruan, Hong; Li, Hongguang] Chinese Acad Sci, Lanzhou Inst Chem Phys, Lab Clean Energy Chem & Mat, Lanzhou 730000, Peoples R China. [Lu, Xiaowei; Li, Hongguang] NIDDK, Carbohydrates Sect, Bioorgan Chem Lab, NIH, 9000 Rockville Pike,Bldg 8,Room 1A21, Room Bethesda, MD 20896 USA. [Cui, Jiwei] Univ Melbourne, Dept Chem & Biomol Engn, Parkville, Vic 3010, Australia. [Liu, Baoyong] Univ Chinese Acad Sci, Beijing 100049, Peoples R China. [Liu, Baoyong] Lanzhou Jiaotong Univ, Sch Chem & Biol Engn, Lanzhou 730070, Peoples R China. RP Li, HG (reprint author), Chinese Acad Sci, Lanzhou Inst Chem Phys, Lab Clean Energy Chem & Mat, Lanzhou 730000, Peoples R China.; Li, HG (reprint author), NIDDK, Carbohydrates Sect, Bioorgan Chem Lab, NIH, 9000 Rockville Pike,Bldg 8,Room 1A21, Room Bethesda, MD 20896 USA. EM hgli@licp.cas.cn FU Hundred Talents Program of Chinese Academy of Sciences [Y20245YBR1]; National Natural Science Foundation of China [21402215, 61474124] FX The authors are grateful for the financial support by the Hundred Talents Program of Chinese Academy of Sciences (Y20245YBR1) and National Natural Science Foundation of China (no. 21402215, 61474124). NR 105 TC 0 Z9 0 U1 11 U2 24 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1385-2728 EI 1875-5348 J9 CURR ORG CHEM JI Curr. Org. Chem. PY 2016 VL 20 IS 14 BP 1502 EP 1511 DI 10.2174/1385272820666151207194453 PG 10 WC Chemistry, Organic SC Chemistry GA DK9UV UT WOS:000375278000006 ER PT J AU Nobel, YR Lodish, MB Raygada, M Del Rivero, J Faucz, FR Abraham, SB Lyssikatos, C Belyavskaya, E Stratakis, CA Zilbermint, M AF Nobel, Yael R. Lodish, Maya B. Raygada, Margarita Del Rivero, Jaydira Faucz, Fabio R. Abraham, Smita B. Lyssikatos, Charalampos Belyavskaya, Elena Stratakis, Constantine A. Zilbermint, Mihail TI Pseudohypoaldosteronism type 1 due to novel variants of SCNN1B gene SO ENDOCRINOLOGY DIABETES AND METABOLISM CASE REPORTS LA English DT Article ID CHANNEL AB Autosomal recessive pseudohypoaldosteronism type 1 (PHA1) is a rare disorder characterized by sodium wasting, failure to thrive, hyperkalemia, hypovolemia and metabolic acidosis. It is due to mutations in the amiloride-sensitive epithelial sodium channel (ENaC) and is characterized by diminished response to aldosterone. Patients may present with life-threatening hyperkalemia, which must be recognized and appropriately treated. A 32-year-old female was referred to the National Institutes of Health (NIH) for evaluation of hyperkalemia and muscle pain. Her condition started in the second week of life, when she was brought to an outside hospital lethargic and unresponsive. At that time, she was hypovolemic, hyperkalemic and acidotic, and was eventually treated with sodium bicarbonate and potassium chelation. At the time of the presentation to the NIH, her laboratory evaluation revealed serum potassium 5.1 mmol/l (reference range: 3.4-5.1 mmol/l), aldosterone 2800 ng/dl (reference range: <= 21 ng/dl) and plasma renin activity 90 ng/ml/h (reference range: 0.6-4.3 ng/ml per h). Diagnosis of PHA1 was suspected. Sequencing of the SCNN1B gene, which codes for ENaC, revealed that the patient is a compound heterozygote for two novel variants (c.1288delC and c.1466+1G>A), confirming the suspected diagnosis of PHA1. In conclusion, we report a patient with novel variants of the SCNN1B gene causing PHA1 with persistent, symptomatic hyperkalemia. C1 [Nobel, Yael R.] Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA. [Lodish, Maya B.; Raygada, Margarita; Faucz, Fabio R.; Abraham, Smita B.; Lyssikatos, Charalampos; Belyavskaya, Elena; Stratakis, Constantine A.; Zilbermint, Mihail] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, BG 10-CRC,Room 1-3216,10 Ctr Dr, Bethesda, MD 20814 USA. [Del Rivero, Jaydira] NCI, Med Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 12N-226, Bethesda, MD 20892 USA. [Zilbermint, Mihail] Johns Hopkins Univ, Sch Med, Div Endocrinol Diabet & Metab, Baltimore, MD 21287 USA. [Zilbermint, Mihail] Suburban Hosp, Bethesda, MD 20814 USA. RP Zilbermint, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, BG 10-CRC,Room 1-3216,10 Ctr Dr, Bethesda, MD 20814 USA.; Zilbermint, M (reprint author), Johns Hopkins Univ, Sch Med, Div Endocrinol Diabet & Metab, Baltimore, MD 21287 USA.; Zilbermint, M (reprint author), Suburban Hosp, Bethesda, MD 20814 USA. EM mihail.zilbermint@nih.gov FU Intramural Research Program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development [00-CH-0160] FX This research work was supported by the Intramural Research Program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development, protocol 00-CH-0160 (Clinical and Molecular Analysis of ACTH-Independent Steroid Hormone Production in Adrenocortical Tissue). The study had a clinical trial registration number of NCT00005927. NR 14 TC 0 Z9 0 U1 1 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND EI 2052-0573 J9 ENDOCRINOL DIAB META JI Endocrinol. Diabetes Metab. Case Rep. PD JAN PY 2016 AR 15-0104 DI 10.1530/EDM-15-0104 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DK5HC UT WOS:000374949900004 ER PT J AU Kleb, B Estecio, MRH Zhang, JX Tzelepid, V Chung, W Jelinek, J Navone, NM Tahir, S Marquez, VE Issa, JP Maity, S Aparicio, A AF Kleb, Brittany Estecio, Marcos R. H. Zhang, Jiexin Tzelepid, Vassiliki Chung, Woonbok Jelinek, Jaroslav Navone, Nora M. Tahir, Salahaldin Marquez, Victor E. Issa, Jean-Pierre Maity, Sankar Aparicio, Ana TI Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas SO EPIGENETICS LA English DT Article DE Androgen receptor; DNA methylation; epigenetics; EZH2; histone methylation; neuroendocrine; prostate cancer; small-cell prostate carcinoma; xenograft ID DNA METHYLATION; CANCER-CELLS; CPG ISLAND; COLON-CANCER; REPRESSION; HYPERMETHYLATION; CHEMOTHERAPY; PROGRESSION; MICROARRAY; VARIANT AB Small cell prostate carcinoma ( SCPC) morphology is rare at initial diagnosis but often emerges during prostate cancer progression and portends a dismal prognosis. It does not express androgen receptor ( AR) or respond to hormonal therapies. Clinically applicable markers for its early detection and treatment with effective chemotherapy are needed. Our studies in patient tumor- derived xenografts ( PDX) revealed that AR- negative SCPC ( AR- SCPC) expresses neural development genes instead of the prostate luminal epithelial genes characteristic of AR- positive castration- resistant adenocarcinomas ( AR+ADENO). We hypothesized that the differences in cellular lineage programs are reflected in distinct epigenetic profiles. To address this hypothesis, we compared the DNA methylation profiles of AR- and ARC PDX using methylated CpG island amplification and microarray ( MCAM) analysis and identified a set of differentially methylated promoters, validated in PDX and corresponding donor patient samples. We used the Illumina 450K platform to examine additional regions of the genome and the correlation between the DNA methylation profiles of the PDX and their corresponding patient tumors. Struck by the low frequency of AR promoter methylation in the AR- SCPC, we investigated this region's specific histone modification patterns by chromatin immunoprecipitation. We found that the AR promoter was enriched in silencing histone modifications ( H3K27me3 and H3K9me2) and that EZH2 inhibition with 3- deazaneplanocin A ( DZNep) resulted in AR expression and growth inhibition in AR SCPC cell lines. We conclude that the epigenome of AR- is distinct from that of AR+ castration- resistant prostate carcinomas, and that the AR-phenotype can be reversed with epigenetic drugs. C1 [Kleb, Brittany] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol Unit 1374, 1515 Holcombe Blvd, Houston, TX 77030 USA. [Estecio, Marcos R. H.] Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Unit 0081, 1515 Holcombe Blvd, Houston, TX 77030 USA. [Zhang, Jiexin] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Unit 1410, 1515 Holcombe Blvd, Houston, TX 77030 USA. [Tzelepid, Vassiliki] Univ Patras, Dept Pathol, Panepistimioupoli Patron, Greece. [Chung, Woonbok; Jelinek, Jaroslav; Issa, Jean-Pierre] Temple Univ, Fels Inst Canc Res & Mol Biol, 3307 N Broad St, Philadelphia, PA 19122 USA. [Navone, Nora M.; Tahir, Salahaldin; Maity, Sankar; Aparicio, Ana] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Unit 1374, 1515 Holcombe Blvd, Houston, TX 77030 USA. [Marquez, Victor E.] NCI, Ctr Canc Res, Bldg 376, Frederick, MD 21701 USA. RP Aparicio, A (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Unit 1374, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM aaparicio@mdanderson.org FU NIH/NCI [P30CA016672, P50CA140388]; Joan Stanford Alexander Family Fund FX The authors wish to acknowledge the sources of funding that made this work possible including the NIH/NCI (under award numbers P30CA016672 (Bioinformatics Shared Resource) and P50CA140388) and the Joan Stanford Alexander Family Fund. NR 33 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1559-2294 EI 1559-2308 J9 EPIGENETICS-US JI Epigenetics PY 2016 VL 11 IS 3 BP 184 EP 193 DI 10.1080/15592294.2016.1146851 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA DL1JC UT WOS:000375387400002 PM 26890396 ER PT J AU Hammer-Hansen, S Bandettini, WP Hsu, LY Leung, SW Shanbhag, S Mancini, C Greve, AM Kober, L Thune, JJ Kellman, P Arai, AE AF Hammer-Hansen, Sophia Bandettini, W. Patricia Hsu, Li-Yueh Leung, Steve W. Shanbhag, Sujata Mancini, Christine Greve, Anders M. Kober, Lars Thune, Jens Jakob Kellman, Peter Arai, Andrew E. TI Mechanisms for overestimating acute myocardial infarct size with gadolinium-enhanced cardiovascular magnetic resonance imaging in humans: a quantitative and kinetic study SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING LA English DT Article DE cardiovascular magnetic resonance imaging; acute myocardial infarction; gadolinium enhancement; gadolinium kinetics; extracellular volume ID CORONARY-ARTERY-DISEASE; DELAYED ENHANCEMENT; ECHO-PLANAR; GADOPENTETATE DIMEGLUMINE; PERIINFARCTION ZONE; FUNCTIONAL RECOVERY; DISTRIBUTION VOLUME; CONTRAST-MEDIA; RISK; MRI AB Aims It remains controversial whether cardiovascular magnetic resonance imaging with gadolinium only enhances acutely infarcted or also salvaged myocardium. We hypothesized that enhancement of salvaged myocardium may be due to altered extracellular volume (ECV) and contrast kinetics compared with normal and infarcted myocardium. If so, these mechanisms could contribute to overestimation of acute myocardial infarction (AMI) size. Methods and results Imagingwas performed at 1.5T <= 7 days after AMI with serial T-1 mapping and volumetric early (5 min post-contrast) and late (20 min post-contrast) gadolinium enhancement imaging. Infarcts were classified as transmural (>75% transmural extent) or non-transmural. Patients with non-transmural infarctions (n = 15) had shorter duration of symptoms before reperfusion (P = 0.02), lower peak troponin (P = 0.008), and less microvascular obstruction (P < 0.001) than patients with transmural infarcts (n = 22). The size of enhancement at 5 min was greater than at 20 min (18.7 +/- 12.7 vs. 12.1 +/- 7.0%, P = 0.003) in non-transmural infarctions, but similar in transmural infarctions (23.0 +/- 10.0 vs. 21.9 +/- 9.9%, P = 0.21). ECV of salvaged myocardium was greater than normal (39.5 +/- 5.8 vs. 24.1 +/- 3.1%) but less than infarcted myocardium (50.5+ 6.0%, both P < 0.001). In kinetic studies of non-transmural infarctions, salvaged and infarcted myocardium had similar T-1 at 4 min but different T-1 at 8-20 min post-contrast. Conclusion Theextent of gadolinium enhancement in AMI is modulated by ECV and contrast kinetics. Image acquisition too early after contrast administration resulted in overestimation of infarct size in non-transmural infarctions due to enhancement of salvaged myocardium. C1 [Hammer-Hansen, Sophia; Bandettini, W. Patricia; Hsu, Li-Yueh; Leung, Steve W.; Shanbhag, Sujata; Mancini, Christine; Greve, Anders M.; Kober, Lars; Thune, Jens Jakob; Kellman, Peter; Arai, Andrew E.] NHLBI, Lab Adv Cardiovasc Imaging, US Dept HHS, NIH, Bldg 10,Room B1D416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA. [Hammer-Hansen, Sophia; Kober, Lars; Thune, Jens Jakob] Rigshosp, Ctr Heart, Dept Med B, DK-2100 Copenhagen, Denmark. [Leung, Steve W.] Univ Kentucky, Dept Med & Radiol, Div Cardiovasc Med, Lexington, KY USA. RP Arai, AE (reprint author), NHLBI, Lab Adv Cardiovasc Imaging, US Dept HHS, NIH, Bldg 10,Room B1D416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA. EM araia@nih.gov RI Leung, Steve/E-5624-2011 OI Leung, Steve/0000-0003-2832-2258 FU Intramural Research Program of the National Heart, Lung, and Blood Institute, National Institutes of Health, USA [Z01 HL006136-03, HL004607-15]; Division of Intramural Research, NHLBI, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute, National Institutes of Health, USA (Z01 HL006136-03 and HL004607-15). Funding to pay the Open Access publication charges for this article was provided by the Division of Intramural Research, NHLBI, National Institutes of Health. NR 32 TC 3 Z9 3 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2047-2404 EI 2047-2412 J9 EUR HEART J-CARD IMG JI Eur. Heart J.-Cardiovasc. Imaging PD JAN 1 PY 2016 VL 17 IS 1 BP 76 EP 84 DI 10.1093/ehjci/jev123 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DL1XE UT WOS:000375425700016 PM 25983233 ER PT J AU Shchyolkina, AK Kaluzhny, DN Borisova, OF Arndt-Jovin, DJ Jovin, TM Zhurkin, VB AF Shchyolkina, Anna K. Kaluzhny, Dmitry N. Borisova, Olga F. Arndt-Jovin, Donna J. Jovin, Thomas M. Zhurkin, Victor B. TI Conformational variability of recombination R-triplex formed by the mammalian telomeric sequence SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article DE R-triplex; telomeric DNA; thermodynamic stability; fluorescence; circular dichroism ID T-LOOPS; ETHIDIUM-BROMIDE; STRAND INVASION; NUCLEIC-ACID; DNA; COMPLEX; HELIX; 2-AMINOPURINE; VISUALIZATION; FLUORESCENCE AB Alignment of three nucleic acids strands, in which the third strand is identical to one of the DNA duplex strands, occurs in various cellular systems. In the case of telomeric t-loops, recognition between the DNA duplex and the homologous single strand is likely to be mediated by proteins through formation of the transient recombination-type R-triplex. Earlier, using 2-aminopurine as a fluorescent reporting base, we evaluated the thermodynamic characteristics of intramolecular R-triplex formed by a mixed nucleotide sequence. Here, we used this approach to explore a propensity of the telomeric TTAGGG repeat to form the R-triplex. The circular dichroism spectral changes detected upon formation of the R-triplex suggest that this process is accompanied by specific conformational changes in DNA, including a local destabilization of the target duplex next to a GGG run revealed by the fluorescence of the reporting 2-aminopurine base. Surprisingly, stability of the R-triplex formed by telomeric sequence depends strikingly on the counter ion, being higher for Na+ than for Li+. Taken together these findings indicate a significant conformational variability of telomeric DNA in the context of recombination-type R-triplex, a phenomenon of possible biological relevance. C1 [Shchyolkina, Anna K.; Kaluzhny, Dmitry N.; Borisova, Olga F.] Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow 119991, Russia. [Arndt-Jovin, Donna J.; Jovin, Thomas M.] Max Planck Inst Biophys Chem, Dept Mol Biol, D-37070 Gottingen, Germany. [Zhurkin, Victor B.] NCI, Lab Cell Biol, NIH, Bethesda, MD 20892 USA. RP Shchyolkina, AK (reprint author), Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow 119991, Russia.; Zhurkin, VB (reprint author), NCI, Lab Cell Biol, NIH, Bethesda, MD 20892 USA. EM ashchyolkina@mail.ru; zhurkin@nih.gov RI Kaluzhny, Dmitry/G-7256-2014 FU Russian Academy of Sciences, Molecular and Cellular Biology Program FX This work was supported by Russian Academy of Sciences, Molecular and Cellular Biology Program. NR 37 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 0739-1102 EI 1538-0254 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PY 2016 VL 34 IS 6 BP 1298 EP 1306 DI 10.1080/07391102.2015.1077344 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA DL0NS UT WOS:000375330300013 PM 26308235 ER PT J AU Kim, SM Romero, R Lee, J Chaemsaithong, P Lee, MW Chaiyasit, N Lee, HJ Yoon, BH AF Kim, Sun Min Romero, Roberto Lee, JoonHo Chaemsaithong, Piya Lee, Min-Woo Chaiyasit, Noppadol Lee, Hyo-Jin Yoon, Bo Hyun TI About one-half of early spontaneous preterm deliveries can be identified by a rapid matrix metalloproteinase-8 (MMP-8) bedside test at the time of mid-trimester genetic amniocentesis SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article; Proceedings Paper CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med DE Amniotic fluid; intra-amniotic inflammation/infection; point-of-care (POC) test; preterm parturition ID AMNIOTIC-FLUID INTERLEUKIN-6; POLYMERASE-CHAIN-REACTION; BLOOD-CELL COUNT; TUMOR-NECROSIS-FACTOR; ACTIVATING PEPTIDE-1 INTERLEUKIN-8; GRAM STAIN EXAMINATION; UMBILICAL-CORD PLASMA; WHITE-MATTER LESIONS; FREE FETAL DNA; PREMATURE RUPTURE AB Objective: Mid-trimester amniocentesis continues to be used for the prenatal diagnosis of chromosomal anomalies and other genetic disorders. Analysis of amniotic fluid obtained at the time of mid-trimester genetic amniocentesis identifies those patients who are at risk for early spontaneous preterm delivery. This is based on a solid body of evidence that found subclinical intra-amniotic inflammation/infection to be causally linked to early spontaneous preterm birth. Although several biomarkers have been proposed to identify intra-amniotic inflammation, the accumulated data suggest that the determination of amniotic fluid matrix metalloproteinase-8 (MMP-8), or neutrophil collagenase, is a powerful predictor of spontaneous preterm delivery. MMP-8 is released by inflammatory cells in response to microbial products or danger signals. A rapid point-of-care test has been developed to determine MMP-8 at the bedside within 20min, and without the requirement of laboratory equipment. The objective of this study was to determine whether an elevation of MMP-8 in the amniotic fluid, measured by a rapid point-of-care test, can identify those patients at risk for spontaneous preterm delivery after a mid-trimester genetic amniocentesis.Study design: A case-control study was designed to obtain amniotic fluid from asymptomatic singleton pregnant women who underwent mid-trimester genetic amniocentesis. An MMP-8 bedside test was performed to analyze the amniotic fluid of 64 patients with early spontaneous preterm delivery (<30 weeks) and 128 matched controls with normal pregnancy outcomes.Results: (1) The MMP-8 bedside test (Yoon's MMP-8 Check) was positive in 42.2% (27/64) of patients with spontaneous preterm delivery but in none (0/128) of the control cases (p<0.001); (2) the MMP-8 bedside test had a sensitivity of 42.2%, and a specificity of 100% in the prediction of spontaneous preterm delivery (<30 weeks) following a mid-trimester genetic amniocentesis; and (3) among the patients with spontaneous preterm delivery, those with a positive MMP-8 bedside test had a significantly higher rate of spontaneous delivery within 2 weeks and 4 weeks of an amniocentesis [40.7% (11/27) versus 5.4% (2/37); 63.0% (17/27) versus 24.3% (9/37)] and a shorter interval-to-delivery period than those with a negative test [interval-to-delivery: median (range), 16 d (0-95 d) versus 42 d (2-91 d); p<0.05 for each].Conclusion: We conclude that 42% of patients with an early spontaneous preterm delivery (<30 weeks) could be identified by a rapid MMP-8 bedside test at the time of their mid-trimester genetic amniocentesis. The MMP-8 bedside test is a powerful predictor of early spontaneous preterm birth in asymptomatic pregnant women. C1 [Kim, Sun Min; Lee, JoonHo; Lee, Min-Woo; Lee, Hyo-Jin; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. [Kim, Sun Min] Seoul Metropolitan Govt Seoul Natl Univ, Boramae Med Ctr, Dept Obstet & Gynecol, Seoul, South Korea. [Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol] NICHD, Perinatol Res Branch,Program Perinatal Res & Obst, Div Intramural Res,Eunice Kennedy Shriver Natl In, NIH,DHHS, Bethesda, MD USA. [Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol] NICHD, Perinatol Res Branch,Program Perinatal Res & Obst, Div Intramural Res,Eunice Kennedy Shriver Natl In, NIH,DHHS, Detroit, MI USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Chaemsaithong, Piya; Chaiyasit, Noppadol] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch,Program Perinatal Res & Obst, Div Intramural Res,Eunice Kennedy Shriver Natl In, NICHD,NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM romeror@mail.nih.gov FU Intramural NIH HHS NR 192 TC 1 Z9 1 U1 2 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2016 VL 29 IS 15 BP 2414 EP U32 DI 10.3109/14767058.2015.1094049 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DK2WN UT WOS:000374775200005 PM 26643648 ER PT J AU Park, JY Romero, R Lee, J Chaemsaithong, P Chaiyasit, N Yoon, BH AF Park, Jee Yoon Romero, Roberto Lee, JoonHo Chaemsaithong, Piya Chaiyasit, Noppadol Yoon, Bo Hyun TI An elevated amniotic fluid prostaglandin F-2 alpha concentration is associated with intra-amniotic inflammation/infection, and clinical and histologic chorioamnionitis, as well as impending preterm delivery in patients with preterm labor and intact membranes SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Acute inflammatory lesions of the placenta; amniocentesis; amniotic fluid infection; funisitis; MMP-8; mycoplasma; prematurity; prostanoids ID CERVICOVAGINAL FETAL FIBRONECTIN; FACTOR-BINDING PROTEIN-1; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; ACTIVATING PEPTIDE-1 INTERLEUKIN-8; MMP-8 BEDSIDE TEST; CERVICAL LENGTH; MICROBIAL INVASION; PREMATURE RUPTURE; HUMAN PARTURITION; TERM LABOR AB Objective: To determine whether an elevated amniotic fluid concentration of prostaglandin F-2 alpha (PGF(2 alpha)) is associated with intra-amniotic inflammation/infection and adverse pregnancy outcomes in patients with preterm labor and intact membranes. Materials and methods: The retrospective cohort study included 132 patients who had singleton pregnancies with preterm labor (<35 weeks of gestation) and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as for genital mycoplasmas. Intra-amniotic inflammation was defined by an elevated amniotic fluid matrix metalloproteinase-8 (MMP-8) concentration (>23 ng/mL). PGF(2 alpha) was measured with a sensitive and specific immunoassay. The amniotic fluid PGF(2 alpha) concentration was considered elevated when it was above the 95th percentile among pregnant women at 15-36 weeks of gestation who were not in labor (>= 170 pg/mL). Results: (1) The prevalence of an elevated amniotic fluid PGF(2 alpha) concentration was 40.2% (53/132) in patients with preterm labor and intact membranes; (2) patients with an elevated amniotic fluid PGF(2 alpha) concentration had a significantly higher rate of positive amniotic fluid culture [19% (10/53) versus 5% (4/79); p = 0.019], intra-amniotic inflammation/infection [49% (26/53) versus 20% (16/79); p = 0.001], spontaneous preterm delivery, clinical and histologic chorioamnionitis, and funisitis, as well as a higher median amniotic fluid MMP-8 concentration and amniotic fluid white blood cell count and a shorter amniocentesis-to-delivery interval than those without an elevated concentration of amniotic fluid PGF(2 alpha) (p < 0.05 for each); and (3) an elevated amniotic fluid PGF(2 alpha) concentration was associated with a shorter amniocentesis-to-delivery interval after adjustment for the presence of intra-amniotic inflammation/infection [hazard ratio 2.1, 95% confidence interval (CI) 1.4-3.1; p = 0.001]. Conclusion: The concentration of PGF(2 alpha) was elevated in the amniotic fluid of 40.2% of patients with preterm labor and intact membranes and is an independent risk factor for intra-amniotic inflammation/infection, impending preterm delivery, chorioamnionitis, and funisitis. C1 [Park, Jee Yoon; Lee, JoonHo; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, 28 Yeongeon Dong, Seoul 110744, South Korea. [Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet,Div Intramural Res, NIH,DHHS, Bethesda, MD USA. [Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet,Div Intramural Res, NIH,DHHS, Detroit, MI USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Chaemsaithong, Piya; Chaiyasit, Noppadol] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, 28 Yeongeon Dong, Seoul 110744, South Korea. EM yoonbh@snu.ac.kr FU Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI12C0768]; Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This research was supported by a grant of the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No. HI12C0768). This research was also supported, in part, by the Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS). NR 215 TC 1 Z9 1 U1 3 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2016 VL 29 IS 16 BP 2563 EP 2572 DI 10.3109/14767058.2015.1094794 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DK6IU UT WOS:000375027200002 PM 26669519 ER PT J AU Kim, SM Romero, R Lee, J Chaemsaithong, P Docheva, N Yoon, BH AF Kim, Sun Min Romero, Roberto Lee, JoonHo Chaemsaithong, Piya Docheva, Nikolina Yoon, Bo Hyun TI Gastric fluid versus amniotic fluid analysis for the identification of intra-amniotic infection due to Ureaplasma species SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Acute histologic chorioamnionitis; amniocentesis; culture; gastric aspirate; genital Mycoplasmas; matrix metalloproteinase-8; neonatal sepsis; preterm birth ID PRETERM PREMATURE RUPTURE; POLYMERASE-CHAIN-REACTION; EARLY-ONSET SEPSIS; BIRTH-WEIGHT INFANTS; MMP-8 BEDSIDE TEST; BLOOD-CELL COUNT; ACUTE HISTOLOGIC CHORIOAMNIONITIS; RESPIRATORY-DISTRESS-SYNDROME; ADVERSE PREGNANCY OUTCOMES; ACUTE INFLAMMATORY LESIONS AB Objective: Early neonatal sepsis is often due to intra-amniotic infection. The stomach of the neonate contains fluid swallowed before and during delivery. The presence of bacteria as well as neutrophils detected by culture or Gram stain of the gastric fluid during the first day of life is suggestive of exposure to bacteria or inflammation. We undertook this study to determine the relationship between gastric fluid analysis and amniotic fluid obtained by transabdominal amniocentesis in the detection of Ureaplasma species, the most frequent microorganisms responsible for intra-amniotic infection. Materials and methods: The study population consisted of 100 singleton pregnant women who delivered preterm neonates (<35 weeks) within 7 days of amniocentesis. Gastric fluid of newborns was obtained by nasogastric intubation on the day of birth. Amniotic fluid and gastric fluid were cultured for genital Mycoplasmas, and polymerase chain reaction (PCR) for Ureaplasma species was performed. Intra-amniotic inflammation was defined as an elevated amniotic fluid matrix metalloproteinase-8 concentration (>23ng/mL). Results: (1) Ureaplasma species were detected by culture or PCR in 18% (18/100) of amniotic fluid samples and in 5% (5/100) of gastric fluid samples; (2) among the amniotic fluid cases positive for Ureaplasma species, these microorganisms were identified in 27.8% (5/18) of gastric fluid samples; (3) none of the cases negative for Ureaplasma species in the amniotic fluid were found to be positive for these microorganisms in the gastric fluid; (4) patients with amniotic fluid positive for Ureaplasma species but with gastric fluid negative for these microorganisms had a significantly higher rate of intra-amniotic inflammation, acute histologic chorioamnionitis, and neonatal death than those with both amniotic fluid and gastric fluid negative for Ureaplasma species; and (5) no significant differences were observed in the rate of intra-amniotic inflammation, acute histologic chorioamnionitis, and neonatal death between patients with amniotic fluid positive for Ureaplasma species but with gastric fluid negative for these microorganisms and those with both amniotic fluid and gastric fluid positive for Ureaplasma species. Conclusions: Gastric fluid analysis has 100% specificity in the identification of intra-amniotic infection with Ureaplasma species. However, the detection of Ureaplasma species by culture or PCR in the gastric fluid of neonates at birth did not identify these microorganisms in two-thirds of cases with microbial invasion of the amniotic cavity. Thus, amniotic fluid analysis is superior to that of gastric fluid in the identification of intra-amniotic infection. C1 [Kim, Sun Min; Lee, JoonHo; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. [Kim, Sun Min] Seoul Metropolitan Govt Seoul Natl Univ, Boramae Med Ctr, Dept Obstet & Gynecol, Seoul, South Korea. [Romero, Roberto; Chaemsaithong, Piya; Docheva, Nikolina] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, Roberto; Chaemsaithong, Piya; Docheva, Nikolina] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Chaemsaithong, Piya; Docheva, Nikolina] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Perinatol Res Branch, 3990 John R St,4 Brush, Detroit, MI 48201 USA. RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea.; Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.; Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.; Romero, R (reprint author), Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.; Romero, R (reprint author), Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.; Romero, R (reprint author), Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.; Romero, R (reprint author), Perinatol Res Branch, 3990 John R St,4 Brush, Detroit, MI 48201 USA. EM romeror@mail.nih.gov; yoonbh@snu.ac.kr FU Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI12C0768]; Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS) FX All authors declare no conflicts of interest. No external financial support was received for this study. This research was supported by a grant of the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI12C0768). This research was also supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS). NR 205 TC 0 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2016 VL 29 IS 16 BP 2579 EP 2587 DI 10.3109/14767058.2015.1098614 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DK6IU UT WOS:000375027200004 PM 26631980 ER PT J AU Dimond, EP Zon, RT Weiner, BI Germain, DS Denicoff, AM Dempsey, K Carrigan, AC Teal, RW Good, MJ McCaskill-Stevens, W Grubbs, SS AF Dimond, Eileen P. Zon, Robin T. Weiner, Bryan I. Germain, Diane St. Denicoff, Andrea M. Dempsey, Kandie Carrigan, Angela C. Teal, Randall W. Good, Marjorie J. McCaskill-Stevens, Worta Grubbs, Stephen S. TI Clinical Trial Assessment of Infrastructure Matrix Tool to Improve the Quality of Research Conduct in the Community SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID CANCER CENTERS PROGRAM; SITES AB Purpose: Several publications have described minimum standards and exemplary attributes for clinical trial sites to improve research quality. The National Cancer Institute (NCI) Community Cancer Centers Program (NCCCP) developed the clinical trial Best Practice Matrix tool to facilitate research program improvements through annual self-assessments and benchmarking. The tool identified nine attributes, each with three progressive levels, to score clinical trial infrastructural elements from less to more exemplary. The NCCCP sites correlated tool use with research program improvements, and the NCI pursued a formative evaluation to refine the interpretability and measurability of the tool. Methods: From 2011 to 2013, 21 NCCCP sites self-assessed their programs with the tool annually. During 2013 to 2014, NCI collaborators conducted a five-step formative evaluation of the matrix tool. Results: Sites reported significant increases in level-three scores across the original nine attributes combined (P<.001). Two specific attributes exhibited significant change: clinical trial portfolio diversity and management (P=.0228) and clinical trial communication (P=.0281). The formative evaluation led to revisions, including renaming the Best Practice Matrix as the Clinical Trial Assessment of Infrastructure Matrix (CT AIM), expanding infrastructural attributes from nine to 11, clarifying metrics, and developing a new scoring tool. Conclusion: Broad community input, cognitive interviews, and pilot testing improved the usability and functionality of the tool. Research programs are encouraged to use the CT AIM to assess and improve site infrastructure. Experience within the NCCCP suggests that the CT AIM is useful for improving quality, benchmarking research performance, reporting progress, and communicating program needs with institutional leaders. The tool model may also be useful in disciplines beyond oncology. C1 Michiana Hematol Oncol, South Bend, IN USA. Univ N Carolina, Chapel Hill, NC USA. UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. NCI, Bethesda, MD 20892 USA. Frederick Natl Lab Canc Res, Leidos Biomed Res, Frederick, MD USA. Helen F Graham Canc Ctr & Res Inst, Newark, DE USA. RP Dimond, EP (reprint author), NCI, 9609 Med Ctr Dr,Room 5E516,MSC 9785, Rockville, MD 20892 USA. EM dimonde@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX Supported by the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. Presented in part at the 50th Annual Meeting of ASCO, Chicago, IL, May 30-June 3, 2014, and the ASCO Quality Care Symposium, Boston, MA, October 17-18, 2014. 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 27 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD JAN PY 2016 VL 12 IS 1 BP 63 EP E35 DI 10.1200/JOP.2015.005181 PG 15 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DJ6LR UT WOS:000374325200023 PM 26627979 ER PT J AU Klepac, P Megiddo, I Grenfell, BT Laxminarayan, R AF Klepac, Petra Megiddo, Itamar Grenfell, Bryan T. Laxminarayan, Ramanan TI Self-enforcing regional vaccination agreements SO JOURNAL OF THE ROYAL SOCIETY INTERFACE LA English DT Article DE transboundary movement; regional cooperation; epidemic dynamics; SIR model; metapopulation ID INTERNATIONAL ENVIRONMENTAL AGREEMENTS; SUB-SAHARAN AFRICA; INFECTIOUS-DISEASES; TRAVEL RESTRICTIONS; POLITICAL-ECONOMY; MEASLES EPIDEMICS; AIR-TRAVEL; DYNAMICS; IMPACT; MENINGITIS AB In a highly interconnected world, immunizing infections are a transboundary problem, and their control and elimination require international cooperation and coordination. In the absence of a global or regional body that can impose a universal vaccination strategy, each individual country sets its own strategy. Mobility of populations across borders can promote free-riding, because a country can benefit from the vaccination efforts of its neighbours, which can result in vaccination coverage lower than the global optimum. Here we explore whether voluntary coalitions that reward countries that join by cooperatively increasing vaccination coverage can solve this problem. We use dynamic epidemiological models embedded in a game-theoretic framework in order to identify conditions in which coalitions are self-enforcing and therefore stable, and thus successful at promoting a cooperative vaccination strategy. We find that countries can achieve significantly greater vaccination coverage at a lower cost by forming coalitions than when acting independently, provided a coalition has the tools to deter free-riding. Furthermore, when economically or epidemiologically asymmetric countries form coalitions, realized coverage is regionally more consistent than in the absence of coalitions. C1 [Klepac, Petra] Univ Cambridge, Dept Appl Math & Theoret Phys, Silver St, Cambridge CB3 9EW, England. [Megiddo, Itamar; Laxminarayan, Ramanan] Ctr Dis Dynam Econ & Policy, Washington, DC 20036 USA. [Grenfell, Bryan T.; Laxminarayan, Ramanan] Princeton Univ, Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Grenfell, Bryan T.] Princeton Univ, Woodrow Wilson Sch Publ & Int Affairs, Princeton, NJ 08544 USA. [Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Laxminarayan, Ramanan] Publ Hlth Fdn India, New Delhi 110070, India. RP Klepac, P (reprint author), Univ Cambridge, Dept Appl Math & Theoret Phys, Silver St, Cambridge CB3 9EW, England. EM pklepac@alum.mit.edu RI Megiddo, Itamar/N-9839-2015 OI Megiddo, Itamar/0000-0001-8391-6660 FU Bill & Melinda Gates Foundation; RAPIDD programme of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; AXA Research Fund FX This research was supported by the Bill & Melinda Gates Foundation, the RAPIDD programme of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health (B.T.G.). P.K. acknowledges the support from AXA Research Fund. NR 60 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1742-5689 EI 1742-5662 J9 J R SOC INTERFACE JI J. R. Soc. Interface PD JAN 1 PY 2016 VL 13 IS 114 AR 20150907 DI 10.1098/rsif.2015.0907 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DK5KO UT WOS:000374959000009 PM 26790996 ER PT J AU Bhutani, M Turkbey, B Tan, E Korde, N Kwok, M Manasanch, EE Tageja, N Mailankody, S Roschewski, M Mulquin, M Carpenter, A Lamping, E Minter, AR Weiss, BM Mena, E Lindenberg, L Calvo, KR Maric, I Usmani, SZ Choyke, PL Kurdziel, K Landgren, O AF Bhutani, Manisha Turkbey, Baris Tan, Esther Korde, Neha Kwok, Mary Manasanch, Elisabet E. Tageja, Nishant Mailankody, Sham Roschewski, Mark Mulquin, Marcia Carpenter, Ashley Lamping, Elizabeth Minter, Alex R. Weiss, Brendan M. Mena, Esther Lindenberg, Liza Calvo, Katherine R. Maric, Irina Usmani, Saad Z. Choyke, Peter L. Kurdziel, Karen Landgren, Ola TI Bone marrow abnormalities and early bone lesions in multiple myeloma and its precursor disease: a prospective study using functional and morphologic imaging SO LEUKEMIA & LYMPHOMA LA English DT Article DE MGUS; smoldering myeloma; multiple myeloma; functional imaging; DCE-MRI; NaF; FDG; PET; CT ID UNDETERMINED SIGNIFICANCE MGUS; MONOCLONAL GAMMOPATHY; PROGNOSTIC-SIGNIFICANCE; FLOW-CYTOMETRY; FDG PET/CT; LONG-TERM; RISK; PROGRESSION; MANAGEMENT; F-18-FDG AB The incidence and importance of bone marrow involvement and/or early bone lesions in multiple myeloma (MM) precursor diseases is largely unknown. This study prospectively compared the sensitivity of several imaging modalities in monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and MM. Thirty patients (10 each with MGUS, SMM and MM) were evaluated with skeletal survey, [F-18]FDG-PET/CT, [F-18]NaF-PET/CT and morphologic dynamic contrast enhanced (DCE)-MRI. An additional 16 SMM patients had skeletal surveys and FDG-PET/CT. Among MGUS patients, DCE-MRI found only one focal marrow abnormality; other evaluations were negative. Among 26 SMM patients, five (19%) were re-classified as MM based on lytic bone lesions on CT and six had unifocal or diffuse marrow abnormality. Among MM, marrow abnormalities were observed on FDG-PET/CT in 8/10 patients and on DCE-MRI in nine evaluable patients. Abnormal NaF uptake was observed only in MM patients with lytic lesions on CT, providing no additional clinical information. C1 [Bhutani, Manisha; Tan, Esther; Korde, Neha; Kwok, Mary; Manasanch, Elisabet E.; Tageja, Nishant; Mailankody, Sham; Roschewski, Mark; Mulquin, Marcia; Carpenter, Ashley; Lamping, Elizabeth; Minter, Alex R.; Weiss, Brendan M.; Landgren, Ola] NCI, Multiple Myeloma Sect, Lymphoid Malignancies Branch, CCR,NIH, Bethesda, MD 20892 USA. [Bhutani, Manisha; Usmani, Saad Z.] Carolinas HealthCare Syst, Levine Canc Inst, Charlotte, NC USA. [Turkbey, Baris; Mena, Esther; Lindenberg, Liza; Choyke, Peter L.; Kurdziel, Karen] NCI, Mol Imaging Program, CCR, NIH, Bethesda, MD 20892 USA. [Korde, Neha; Landgren, Ola] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. [Manasanch, Elisabet E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Weiss, Brendan M.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Calvo, Katherine R.; Maric, Irina] NIH, Hematol Sect, DLM, CC, Bldg 10, Bethesda, MD 20892 USA. RP Landgren, O (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10065 USA. EM landgrec@mskcc.org NR 21 TC 2 Z9 2 U1 2 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2016 VL 57 IS 5 BP 1114 EP 1121 DI 10.3109/10428194.2015.1090572 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA DK6IS UT WOS:000375027000019 PM 26690712 ER PT J AU Wang, RP Gu, XQ Dai, WQ Ye, J Lu, F Chai, YF Fan, GR Gonzalez, FJ Duan, GL Qi, YP AF Wang, Renping Gu, Xueqin Dai, Weiquan Ye, Jun Lu, Feng Chai, Yifeng Fan, Guorong Gonzalez, Frank J. Duan, Gengli Qi, Yunpeng TI A lipidomics investigation into the intervention of celastrol in experimental colitis SO MOLECULAR BIOSYSTEMS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CHROMATOGRAPHY-MASS SPECTROMETRY; ALPHA-DEPENDENT EXACERBATION; EXPERIMENTAL MURINE COLITIS; COA DESATURASE 1; ULCERATIVE-COLITIS; CROHNS-DISEASE; METABOLOMICS REVEALS; OXIDATIVE STRESS AB Celastrol is well known for its anti-inflammatory and anti-cancer effects. In this study, the efficacy of celastrol against dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD) in mice was established and the mechanism was investigated using lipidomics. Celastrol treatment significantly alleviated DSS-induced colitis in mice, as revealed by the body weight, colon length, scores of rectal bleeding and diarrhea, serum TNF-alpha level, and histological analysis results. Lipidomics analysis based on UPLC/MS revealed characteristic changes in the metabolic profiles of the colitis mice, with altered levels of lipid markers associated with IBD, including LPC18 : 0, LPC18 : 1, LPC18 : 2, sphingomyelin (SM), and increased LPC18 : 0/LPC18 : 1 and LPC18 : 0/LPC18 : 2 ratios. For the celastrol-treated colitis mice, however, levels of the above lipid markers were restored, together with recovered saturated LPC/unsaturated LPC ratios. Accordingly, using GC-MS analysis, increased stearic acid (C18 : 0)/oleic acid (C18 : 1) and stearic acid (C18 : 0)/linoleic acid (C18 : 2) ratios were observed in colitis mice, which were later recovered after celastrol treatment. Quantitative real-time PCR analysis revealed that the liver expression of stearoyl-coenzyme A desaturase 1 (SCD1), the key enzyme controlling the desaturation of saturated fatty acid, was dramatically inhibited in IBD mice, and was obviously recovered after celastrol treatment. These results suggest that the increased saturated LPC/unsaturated LPC (and saturated fatty acid/unsaturated fatty acid) ratios associated with SCD1 down-regulation could be regarded as biomarkers of colitis, and celastrol alleviates DSS-induced colitis partially via up-regulation of SCD1, restoring the altered balance between stearic acid-and oleic acid-derived lipid species, which plays an important role in alleviating colitis. In all, this study provided the scientific basis for further development of celastrol in treating IBD. C1 [Wang, Renping; Gu, Xueqin; Dai, Weiquan; Lu, Feng; Chai, Yifeng; Fan, Guorong; Qi, Yunpeng] Second Mil Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shanghai 200433, Peoples R China. [Ye, Jun] Shanghai Zhabei Inst Food & Drug Control, Shanghai 200436, Peoples R China. [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Duan, Gengli; Qi, Yunpeng] Fudan Univ, Sch Pharm, Dept Pharmaceut Anal, Shanghai 201203, Peoples R China. RP Qi, YP (reprint author), Second Mil Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shanghai 200433, Peoples R China.; Duan, GL; Qi, YP (reprint author), Fudan Univ, Sch Pharm, Dept Pharmaceut Anal, Shanghai 201203, Peoples R China. EM glduan@shmu.edu.cn; qiyunpeng@smmu.edu.cn FU China Postdoctoral Science Foundation [2015M581534]; Li-Shi-Zhen Young Scientist Project of School of Pharmacy at the Second Military Medical University, Shanghai, China FX This study was supported by Project Funded by China Postdoctoral Science Foundation (2015M581534), and Li-Shi-Zhen Young Scientist Project of School of Pharmacy at the Second Military Medical University, Shanghai, China. NR 66 TC 0 Z9 0 U1 6 U2 13 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X EI 1742-2051 J9 MOL BIOSYST JI Mol. Biosyst. PY 2016 VL 12 IS 5 BP 1436 EP 1444 DI 10.1039/c5mb00864f PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DK5CG UT WOS:000374936700004 PM 27021137 ER PT J AU Llauro, A Luque, D Edwards, E Trus, BL Avera, J Reguera, D Douglas, T de Pablo, PJ Caston, JR AF Llauro, Aida Luque, Daniel Edwards, Ethan Trus, Benes L. Avera, John Reguera, David Douglas, Trevor de Pablo, Pedro J. Caston, Jose R. TI Cargo-shell and cargo-cargo couplings govern the mechanics of artificially loaded virus-derived cages SO NANOSCALE LA English DT Article ID ATOMIC-FORCE MICROSCOPY; COAT PROTEIN; ELECTRON-MICROSCOPY; BACTERIOPHAGE P22; CAPSID MATURATION; VIRAL CAPSIDS; DNA; GENOME; ENCAPSULATION; MICROCOMPARTMENTS AB Nucleic acids are the natural cargo of viruses and key determinants that affect viral shell stability. In some cases the genome structurally reinforces the shell, whereas in others genome packaging causes internal pressure that can induce destabilization. Although it is possible to pack heterologous cargoes inside virus-derived shells, little is known about the physical determinants of these artificial nanocontainers' stability. Atomic force and three-dimensional cryo-electron microscopy provided mechanical and structural information about the physical mechanisms of viral cage stabilization beyond the mere presence/absence of cargos. We analyzed the effects of cargo-shell and cargo-cargo interactions on shell stability after encapsulating two types of proteinaceous payloads. While bound cargo to the inner capsid surface mechanically reinforced the capsid in a structural manner, unbound cargo diffusing freely within the shell cavity pressurized the cages up to similar to 30 atm due to steric effects. Strong cargo-cargo coupling reduces the resilience of these nanocompartments in similar to 20% when bound to the shell. Understanding the stability of artificially loaded nanocages will help to design more robust and durable molecular nanocontainers. C1 [Llauro, Aida; de Pablo, Pedro J.] Univ Autonoma Madrid, Dept Condensed Matter Phys, E-28049 Madrid, Spain. [Luque, Daniel; Caston, Jose R.] Ctr Nacl Biotecnol CNB CSIC, Dept Struct Macromol, Darwin 3, Madrid 28049, Spain. [Luque, Daniel] Inst Salud Carlos III, Ctr Nacl Microbiol, Madrid 28220, Spain. [Edwards, Ethan; Avera, John; Douglas, Trevor] Indiana Univ, Dept Chem, Bloomington, IN 47405 USA. [Trus, Benes L.] NIH, Imaging Sci Lab, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. [Reguera, David] Univ Barcelona, Fac Fis, Dept Fis Fonamental, Marti & Franques 1, E-08028 Barcelona, Spain. [de Pablo, Pedro J.] Univ Autonoma Madrid, Solid Condensed Matter Inst IFIMAC, E-28049 Madrid, Spain. RP de Pablo, PJ (reprint author), Univ Autonoma Madrid, Dept Condensed Matter Phys, E-28049 Madrid, Spain.; Caston, JR (reprint author), Ctr Nacl Biotecnol CNB CSIC, Dept Struct Macromol, Darwin 3, Madrid 28049, Spain.; de Pablo, PJ (reprint author), Univ Autonoma Madrid, Solid Condensed Matter Inst IFIMAC, E-28049 Madrid, Spain. EM p.j.depablo@uam.es; jrcaston@cnb.csic.es RI Caston, Jose/L-5896-2014; De Pablo Gomez, Pedro/L-9392-2014; Reguera, David/L-8580-2014; Luque, Daniel/I-6467-2015; Douglas, Trevor/F-2748-2011 OI Caston, Jose/0000-0003-2350-9048; De Pablo Gomez, Pedro/0000-0003-2386-3186; Reguera, David/0000-0001-6395-6112; Luque, Daniel/0000-0002-0151-6020; FU Spanish Ministry of Economy and Competitivity [FIS2011-22603, FIS2011-16090-E, FIS2014-59562-R, FIS2015-71108-REDT, BFU2014-55475-R]; Comunidad Autonoma de Madrid [S2013/MIT-2807]; Fundacion BBVA; NSF-BMAT [DMR-1507282]; Intramural Research Program of the NIH; Center for Information Technology FX We thank C. Mark for editorial assistance. This work was supported by grants from the Spanish Ministry of Economy and Competitivity (FIS2011-22603 and FIS2011-16090-E to DR, FIS2014-59562-R to PJP, FIS2015-71108-REDT to DR, PJP and JRC and BFU2014-55475-R to JRC), the Comunidad Autonoma de Madrid (S2013/MIT-2807 to JRC), Fundacion BBVA to PJP, NSF-BMAT DMR-1507282 to TD, and the Intramural Research Program of the NIH and the Center for Information Technology (to BLT). NR 66 TC 3 Z9 3 U1 7 U2 12 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2016 VL 8 IS 17 BP 9328 EP 9336 DI 10.1039/c6nr01007e PG 9 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA DK9XS UT WOS:000375285800031 PM 27091107 ER PT J AU Huang, XL Zhan, SN Xu, HY Meng, XW Xiong, YH Chen, XY AF Huang, Xiaolin Zhan, Shengnan Xu, Hengyi Meng, Xianwei Xiong, Yonghua Chen, Xiaoyuan TI Ultrasensitive fluorescence immunoassay for detection of ochratoxin A using catalase-mediated fluorescence quenching of CdTe QDs SO NANOSCALE LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; QUANTUM DOTS; QUANTITATIVE DETECTION; PLASMONIC ELISA; AFLATOXIN B-1; NAKED EYE; ENZYME; NANOPARTICLES; ANTIBODY; PROTEINS AB Herein, for the first time we report an improved competitive fluorescent enzyme linked immunosorbent assay (ELISA) for the ultrasensitive detection of ochratoxin A (OTA) by using hydrogen peroxide (H2O2)-induced fluorescence quenching of mercaptopropionic acid-modified CdTe quantum dots (QDs). In this immunoassay, catalase (CAT) was labeled with OTA as a competitive antigen to connect the fluorescence signals of the QDs with the concentration of the target. Through the combinatorial use of H2O2-induced fluorescence quenching of CdTe QDs as a fluorescence signal output and the ultrahigh catalytic activity of CAT to H2O2, our proposed method could be used to perform a dynamic linear detection of OTA ranging from 0.05 pg mL(-1) to 10 pg mL(-1). The half maximal inhibitory concentration was 0.53 pg mL(-1) and the limit of detection was 0.05 pg mL(-1). These values were approximately 283-and 300-folds lower than those of horseradish peroxidase (HRP)-based conventional ELISA, respectively. The reported method is accurate, highly reproducible, and specific against other mycotoxins in agricultural products as well. In summary, the developed fluorescence immunoassay based on H2O2-induced fluorescence quenching of CdTe QDs can be used for the rapid and highly sensitive detection of mycotoxins or haptens in food safety monitoring. C1 [Huang, Xiaolin; Zhan, Shengnan; Xu, Hengyi; Xiong, Yonghua] Nanchang Univ, State Key Lab Food Sci & Technol, Nanchang 330047, Peoples R China. [Meng, Xianwei] Chinese Acad Sci, Tech Inst Phys & Chem, Ctr Micronanomat & Technol, Lab Controllable Preparat & Applicat Nanomat, Beijing 100190, Peoples R China. [Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. RP Xiong, YH (reprint author), Nanchang Univ, State Key Lab Food Sci & Technol, Nanchang 330047, Peoples R China.; Chen, XY (reprint author), NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. EM yhxiongchen@163.com; shawn.chen@nih.gov FU National Basic Research Program of China [2013CB127804]; Training Plan for the Main Subject of Academic Leaders of Jiangxi Province [20142BCB22004]; Training Plan for the Young Scientist (Jinggang Star) of Jiangxi Province [20142BCB23004]; Innovation Fund Designated for Graduate Students of Nanchang University [cx2015107]; Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX This work was supported in part by the National Basic Research Program of China (2013CB127804), the Training Plan for the Main Subject of Academic Leaders of Jiangxi Province (20142BCB22004), the Training Plan for the Young Scientist (Jinggang Star) of Jiangxi Province (20142BCB23004), the Innovation Fund Designated for Graduate Students of Nanchang University (cx2015107), and the Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 49 TC 3 Z9 3 U1 19 U2 55 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2016 VL 8 IS 17 BP 9390 EP 9397 DI 10.1039/c6nr01136e PG 8 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA DK9XS UT WOS:000375285800038 PM 27093176 ER PT J AU Hennessy, E Ornstein, JT Economos, CD Herzog, JB Lynskey, V Coffield, E Hammond, RA AF Hennessy, Erin Ornstein, Joseph T. Economos, Christina D. Herzog, Julia Bloom Lynskey, Vanessa Coffield, Edward Hammond, Ross A. TI Designing an Agent-Based Model for Childhood Obesity Interventions: A Case Study of ChildObesity 180 SO PREVENTING CHRONIC DISEASE LA English DT Article ID COMPLEX-SYSTEMS; HEALTH; VALIDATION; DYNAMICS; SCIENCE AB Complex systems modeling can provide useful insights when designing and anticipating the impact of public health interventions. We developed an agent-based, or individual-based, computation model (ABM) to aid in evaluating and refining implementation of behavior change interventions designed to increase physical activity and healthy eating and reduce unnecessary weight gain among school-aged children. The potential benefits of applying an ABM approach include estimating outcomes despite data gaps, anticipating impact among different populations or scenarios, and exploring how to expand or modify an intervention. The practical challenges inherent in implementing such an approach include data resources, data availability, and the skills and knowledge of ABM among the public health obesity intervention community. The aim of this article was to provide a step-by-step guide on how to develop an ABM to evaluate multifaceted interventions on childhood obesity prevention in multiple settings. We used data from 2 obesity prevention initiatives and public-use resources. The details and goals of the interventions, overview of the model design process, and generalizability of this approach for future interventions is discussed. C1 [Hennessy, Erin] NCI, NIH, 9609 Med Ctr Dr, Rockville, MD 20852 USA. [Ornstein, Joseph T.] Univ Michigan, Dept Polit Sci, Ann Arbor, MI 48109 USA. [Economos, Christina D.; Herzog, Julia Bloom; Lynskey, Vanessa] Tufts Univ, Friedman Sch Nutr Sci & Policy, ChildObes 180, Boston, MA 02111 USA. [Coffield, Edward] Hofstra Univ, Dept Hlth Profess, Hempstead, NY 11550 USA. [Hammond, Ross A.] Brookings Inst, Ctr Social Dynam & Policy, Washington, DC 20036 USA. RP Hennessy, E (reprint author), NCI, NIH, 9609 Med Ctr Dr, Rockville, MD 20852 USA. EM erin.hennessy@nih.gov FU Robert Wood Johnson Foundation; JPB Foundation FX The modeler (J.T.O.) and the obesity content expert (E.H.) contributed equally to this transdisciplinary work. Funding for this study was provided by the Robert Wood Johnson Foundation and the JPB Foundation. When this work began, Dr Hennessy was a Cancer Prevention Fellow at the National Cancer Institute and is now affiliated with Leidos Biomedical Research, Inc. NR 25 TC 1 Z9 1 U1 7 U2 16 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD JAN PY 2016 VL 13 AR E04 DI 10.5888/pcd13.150414 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DK8SV UT WOS:000375199500004 PM 26741998 ER PT J AU Goergen, AF Ashida, S Skapinsky, K de Heer, HD Wilkinson, AV Koehly, LM AF Goergen, Andrea F. Ashida, Sato Skapinsky, Kaley de Heer, Hendrik D. Wilkinson, Anna V. Koehly, Laura M. TI What You Don't Know: Improving Family Health History Knowledge among Multigenerational Families of Mexican Origin SO PUBLIC HEALTH GENOMICS LA English DT Article DE Diabetes; Family health history; Heart disease; Mexican-Americans ID AMERICAN ADULTS; CLINICAL-TRIAL; HEART-DISEASE; PRIMARY-CARE; SOCIAL-CLASS; BARRIERS; PREVENTION; AWARENESS; PROGRAM; WOMEN AB Background: This study investigated diabetes and heart disease family health history (FHH) knowledge and changes after providing personalized disease risk feedback. Methods: A total of 497 adults from 162 families of Mexican origin were randomized by household to conditions based on feedback recipient and content. Each provided personal and relatives' diabetes and heart disease diagnoses and received feedback materials following baseline assessment. Multivariate models were fitted to identify factors associated with the rate of 'don't know' FHH responses. Results: At baseline, US nativity was associated with a higher 'don't know' response rate (p = 0.002). Though confounded by country of birth, younger age showed a trend toward higher 'don't know' response rates. Overall, average 'don't know' response rates dropped from 20 to 15% following receipt of feedback (p < 0.001). An intervention effect was noted, as 'don't know' response rates decreased more in households where one family member (vs. all) received supplementary risk assessments (without behavioral recommendations; p = 0.011). Conclusions: Limited FHH knowledge was noted among those born in the US and younger participants, representing a key population to reach with intervention efforts. The intervention effect suggests that 'less is more', indicating the potential for too much information to limit health education program effectiveness. (C) 2016 S. Karger AG, Basel C1 [Goergen, Andrea F.; Ashida, Sato; Skapinsky, Kaley; de Heer, Hendrik D.; Koehly, Laura M.] NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr,Bldg 31,Rm B1B54, Bethesda, MD 20892 USA. [Ashida, Sato] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. [de Heer, Hendrik D.] No Arizona Univ, Dept Phys Therapy & Athlet Training, Flagstaff, AZ 86011 USA. [Wilkinson, Anna V.] Univ Texas Sch Publ Hlth, Austin Reg Campus, Austin, TX USA. RP Koehly, LM (reprint author), NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr,Bldg 31,Rm B1B54, Bethesda, MD 20892 USA. EM koehlyl@mail.nih.gov FU Intramural Research Program of the National Human Genome Research Institute at the National Institutes of Health [Z01HG200335]; National Cancer Institute [CA126988]; Duncan Family Institute for Cancer Prevention and Risk Assessment FX We would like to extend our gratitude to our research participants, and everyone on the Project RAMA and Mano a Mano teams at the University of Texas M.D. Anderson Cancer Center. This study was supported by the Intramural Research Program of the National Human Genome Research Institute at the National Institutes of Health (Z01HG200335 to L.M.K.). Dr. Anna V. Wilkinson is funded by the National Cancer Institute (CA126988). The Mano a Mano cohort is supported by funds collected pursuant to the Comprehensive Tobacco Settlement of 1998 and appropriated by the 76th legislature to The University of Texas MD Anderson Cancer Center, and by the Duncan Family Institute for Cancer Prevention and Risk Assessment. NR 44 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 EI 1662-8063 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2016 VL 19 IS 2 BP 93 EP 101 DI 10.1159/000443473 PG 9 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA DK9GN UT WOS:000375239000004 PM 26854931 ER PT J AU Aesif, SW Kuipers, I DePalma, L AF Aesif, S. W. Kuipers, I. DePalma, L. TI The relevance of tissue thiol histochemistry to diagnostic hematopathology SO BIOTECHNIC & HISTOCHEMISTRY LA English DT Article DE cysteine; disulfide; glutathionylation; lymphoma; mucin; nitrosylation; oxidation; redox; reduction; thiols ID S-GLUTATHIONYLATION; IN-SITU; REDOX SWITCHES; DISULFIDES; PROTEINS; VISUALIZATION; ENZYMES; REAGENT AB Expression analyses suggest that alterations of the antioxidant state of some diffuse large B-cell lymphomas can assist prognosis; reversibly oxidized thiols may serve as a surrogate marker for identifying such cases. Little is known about the distribution of free thiols and reversibly oxidized thiols in human tissues. We developed a staining technique that enables visualization of tissue thiols in situ using bright field microscopy and validated it using gastrointestinal tissue specimens. We used our thiol staining technique to assess benign tonsillectomy and diffuse large B-cell lymphoma specimens. The gastrointestinal series revealed the presence of free thiols within epithelial cells and cells of the lamina propria. Staining for reversibly oxidized thiols was robust in gastric foveolar cells, intestinal goblet cells and the mucus they produce. Tonsillectomy specimens exhibited diffuse presence of free thiols. Staining for reversibly oxidized thiols was confined to germinal center macrophages and sinus histiocytes. Among the diffuse large B-cell lymphoma specimens, we observed strong staining for free thiols within malignant cells. By contrast to benign B-cells, the malignant cells demonstrated pronounced and diffuse staining for reversibly oxidized thiols. We demonstrated intrinsic differences between benign and malignant cells. C1 [Aesif, S. W.; DePalma, L.] George Washington Univ, Dept Pathol, 2120 L St NW,Suite 200, Washington, DC 20037 USA. [DePalma, L.] George Washington Univ, Dept Anat & Regenerat Biol, Washington, DC USA. [Kuipers, I.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. RP DePalma, L (reprint author), George Washington Univ, Dept Pathol, 2120 L St NW,Suite 200, Washington, DC 20037 USA. EM ldepalma@mfa.gwu.edu FU George Washington University Medical Faculty Associates FX Our work was supported by The George Washington University Medical Faculty Associates. We thank Dr. Laura Taylor for retrieval of cases and the Research Pathology Core Laboratory at George Washington University for use of reagents and equipment. NR 27 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1052-0295 EI 1473-7760 J9 BIOTECH HISTOCHEM JI Biotech. Histochem. PY 2016 VL 91 IS 4 BP 255 EP 262 DI 10.3109/10520295.2016.1142610 PG 8 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA DK0VI UT WOS:000374629900005 PM 26984510 ER PT J AU Acosta, MF Muralidharan, P Meenach, SA Hayes, D Black, SM Mansour, HM AF Acosta, Maria F. Muralidharan, Priya Meenach, Samantha A. Hayes, Don, Jr. Black, Stephen M. Mansour, Heidi M. TI In Vitro Pulmonary Cell Culture in Pharmaceutical Inhalation Aerosol Delivery: 2-D, 3-D, and In Situ Bioimpactor Models SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Pulmonary delivery; aerosol deposition; lung cell culture; air-liquid interface (ALI) culture; liquid covered culture (LCC); multistage cascade impactors; two-dimensional culture; three-dimensional culture ID BRONCHIAL EPITHELIAL-CELLS; AIR-LIQUID INTERFACE; DRUG-DELIVERY; RESPIRATORY-TRACT; PHYSICOCHEMICAL CHARACTERIZATION; LUNG; DEPOSITION; TRANSPORT; PARTICLES; BARRIER AB Background: The use of non-invasive inhaled aerosols for pulmonary drug delivery continues to grow. This is due to the many unique advantages this delivery route offers for the treatment of both local and systemic diseases. The physicochemical properties of the formulated drugs as well as the physiology of the lungs play a key role in both the deposition and absorption of the particles. The airway and the alveolar epithelium are targets for the treatment of respiratory diseases. However, particles have to overcome biological barriers before they reach their target and produce an effect. Methods: In vitro aerosol dispersion performance (i.e. aerodynamic size and aerodynamic size distribution) of inhalable particles is quantified by inertial impaction, as required by regulatory agencies for an investigational pharmaceutical inhalation aerosol formulation to be approved for use in patients as a marketed pharmaceutical product. Using inertial impaction in conjunction with cell cultures of various pulmonary cells in situ as bioimpactors has unique aspects in correlating aerodynamic properties with pulmonary cellular behavior including viability and uptake. These can be as co-culture or in single culture, as 3-D multicellular spheroids or 2-D cellular monolayer using different conditions to grow them, such as air-liquid interface culture (ALI) or in liquid covered culture (LCC). Results: evaluation of the currently available in vitro models and the challenges in developing reliable cellular tools to predict the deposition of inhalable particles in the lungs as a function of aerodynamic particle properties is presented in the manuscript. Conclusion: The mechanistic aerodynamic and biophysical properties of inhaled aerosol particles on the entire respiratory tract at the cellular level based on aerodynamic size and aerodynamic size distribution will be better understood with the development of in vitro methods which are described in this work. C1 [Acosta, Maria F.; Muralidharan, Priya; Mansour, Heidi M.] Univ Arizona, Coll Pharm, Skaggs Pharmaceut Sci Ctr, 1703 USA E Mabel St, Tucson, AZ 85721 USA. [Meenach, Samantha A.] Univ Rhode Isl, Dept Chem Engn, Kingston, RI 02881 USA. [Meenach, Samantha A.] Univ Rhode Isl, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA. [Hayes, Don, Jr.] Ohio State Univ, Coll Med, Dept Pediat, Lung Transplant Program, Columbus, OH 43205 USA. [Hayes, Don, Jr.] Ohio State Univ, Coll Med, Dept Pediat, Heart Lung Transplant Program, Columbus, OH 43205 USA. [Hayes, Don, Jr.] Ohio State Univ, Coll Med, Dept Internal Med, Lung Transplant Program, Columbus, OH 43205 USA. [Hayes, Don, Jr.] Ohio State Univ, Coll Med, Dept Internal Med, Heart Lung Transplant Program, Columbus, OH 43205 USA. [Hayes, Don, Jr.] Ohio State Univ, Coll Med, Davis Heart & Lung Res Inst, Columbus, OH 43205 USA. [Black, Stephen M.; Mansour, Heidi M.] Univ Arizona, Div Translat & Regenerat Med, Dept Med, Tucson, AZ 85724 USA. [Mansour, Heidi M.] Univ Arizona, Inst Environm, Tucson, AZ 85721 USA. [Mansour, Heidi M.] Univ Arizona, Ctr Comprehens Canc, Natl Canc Inst, Tucson, AZ 85721 USA. [Mansour, Heidi M.] Univ Arizona, Res Inst BIO5, Tucson, AZ 85721 USA. RP Mansour, HM (reprint author), Univ Arizona, Coll Pharm, Skaggs Pharmaceut Sci Ctr, 1703 USA E Mabel St, Tucson, AZ 85721 USA. EM mansour@pharmacy.arizona.edu FU CONACyT (National Council of Science and Technology of Mexico); NIH NIAID; Cureveda grant FX The authors gratefully acknowledge the CONACyT (National Council of Science and Technology of Mexico) Fellowship awarded to Maria F. Acosta. Partial support from NIH NIAID & Cureveda grants awarded to HMM are gratefully acknowledged. The authors thank Dr. Aikseng Ooi, Dr. Todd Camenisch, and Dr. Donna Zhang for access to inverted microscopes with digital camera acquisition. NR 62 TC 1 Z9 1 U1 4 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2016 VL 22 IS 17 BP 2522 EP 2531 DI 10.2174/1381612822666160202142104 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DK8AM UT WOS:000375148900008 PM 26831643 ER PT J AU Arcos-Burgos, M Acosta, MT Martinez, AF Muenke, M Enriori, PJ Mastronardi, CA AF Arcos-Burgos, Mauricio Acosta, Maria T. Martinez, Ariel F. Muenke, Maximilian Enriori, Pablo J. Mastronardi, Claudio A. TI Neural Plasticity in Obesity and Psychiatric Disorders SO NEURAL PLASTICITY LA English DT Editorial Material ID BODY-MASS INDEX; BIDIRECTIONAL RELATIONSHIP; DEPRESSION C1 [Arcos-Burgos, Mauricio; Mastronardi, Claudio A.] Australian Natl Univ, John Curtin Sch Med Res, Dept Genome Sci, Genom & Predict Med Grp, Canberra, ACT 2601, Australia. [Acosta, Maria T.; Martinez, Ariel F.; Muenke, Maximilian] NHGRI, NIH, Bethesda, MD 20892 USA. [Acosta, Maria T.] George Washington Univ, Dept Neurol & Pediat, Washington, DC 20052 USA. [Enriori, Pablo J.] Monash Univ, Dept Physiol, Melbourne, Vic 3800, Australia. RP Arcos-Burgos, M (reprint author), Australian Natl Univ, John Curtin Sch Med Res, Dept Genome Sci, Genom & Predict Med Grp, Canberra, ACT 2601, Australia. EM mauricio.arcos-burgos@anu.edu.au NR 10 TC 0 Z9 0 U1 2 U2 2 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2016 AR 6053871 DI 10.1155/2016/6053871 PG 3 WC Neurosciences SC Neurosciences & Neurology GA DJ7WF UT WOS:000374423200001 ER PT J AU Edberg, M Hayes, BE Montgomery-Rice, V Tchounwou, PB AF Edberg, Mark Hayes, Barbara E. Montgomery-Rice, Valerie Tchounwou, Paul B. TI The 2014 Minority Health and Health Disparities Grantees' Conference SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Editorial Material AB Health disparities have been defined as a particular type of health difference closely linked with social, economic and/or environmental disadvantage. The National Institute on Minority Health and Health Disparities (NIMHD) at the National Institutes of Health, has a comprehensive portfolio of grants that fund scientific research to improve racial/ethnic minority health and eliminate health disparities. The 2014 Minority Health and Health Disparities Grantees' Conference highlighted excellence and innovation in biological, environmental, sociocultural, clinical and behavioral research supported by NIMHD. This special issue of the International Journal of Environmental Research and Public Health includes peer-reviewed publications from investigators who participated in this conference. C1 [Edberg, Mark] George Washington Univ, Columbian Coll Arts & Sci, Dept Anthropol, 2110 G St NW, Washington, DC 20052 USA. [Hayes, Barbara E.] Texas So Univ, Coll Pharm & Hlth Sci, Gray Hall,3100 Cleburne St, Houston, TX 77004 USA. [Montgomery-Rice, Valerie] Morehouse Sch Med, 720 Westview Dr SW, Atlanta, GA 30310 USA. [Tchounwou, Paul B.] Jackson State Univ, Coll Sci Engn & Technol, RCMI Ctr Environm Hlth, 1400 Lynch St,Box 18750, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, RCMI Ctr Environm Hlth, 1400 Lynch St,Box 18750, Jackson, MS 39217 USA. EM medberg@gwu.edu; hayes_be@tsu.edu; vmrice@msm.edu; paul.b.tchounwou@jsums.edu NR 9 TC 0 Z9 0 U1 1 U2 1 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD JAN PY 2016 VL 13 IS 1 AR 57 DI 10.3390/ijerph13010057 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA DJ4OO UT WOS:000374186100083 ER PT J AU Skipper, A Sims, JN Yedjou, CG Tchounwou, PB AF Skipper, Anthony Sims, Jennifer N. Yedjou, Clement G. Tchounwou, Paul B. TI Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE cadmium chloride; HepG(2) cells; cytotoxicity; oxidative stress; DNA damage; apoptosis ID DIPLOID HUMAN FIBROBLASTS; ESCHERICHIA-COLI; ANTIOXIDANT ENZYMES; LIPID-PEROXIDATION; EPITHELIAL-CELLS; MAMMALIAN-CELLS; COMET ASSAY; RAT-LIVER; EXPOSURE; MECHANISMS AB Cadmium is a heavy metal that has been shown to cause its toxicity in humans and animals. Many documented studies have shown that cadmium produces various genotoxic effects such as DNA damage and chromosomal aberrations. Ailments such as bone disease, renal damage, and several forms of cancer are attributed to overexposure to cadmium. Although there have been numerous studies examining the effects of cadmium in animal models and a few case studies involving communities where cadmium contamination has occurred, its molecular mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG(2)) cells. To test our hypothesis, cell viability was determined by MTT assay. Lipid hydroperoxide content stress was estimated by lipid peroxidation assay. Genotoxic damage was tested by the means of alkaline single cell gel electrophoresis (Comet) assay. Cell apoptosis was measured by flow cytometry assessment (Annexin-V/PI assay). The result of MTT assay indicated that cadmium chloride induces toxicity to HepG2 cells in a concentration-dependent manner, showing a 48 hr-LD50 of 3.6 mu g/mL. Data generated from lipid peroxidation assay resulted in a significant (p < 0.05) increase of hydroperoxide production, specifically at the highest concentration tested. Data obtained from the Comet assay indicated that cadmium chloride causes DNA damage in HepG(2) cells in a concentration-dependent manner. A strong concentration-response relationship (p < 0.05) was recorded between annexin V positive cells and cadmium chloride exposure. In summary, these in vitro studies provide clear evidence that cadmium chloride induces oxidative stress, DNA damage, and programmed cell death in human liver carcinoma (HepG(2)) cells. C1 [Skipper, Anthony; Yedjou, Clement G.; Tchounwou, Paul B.] Jackson State Univ, Coll Sci Engn & Technol, NIH, Mol Toxicol Res Lab,Ctr Environm Hlth, 1400 Lynch St,Box 18540, Jackson, MS 39217 USA. [Sims, Jennifer N.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Bookline Ave, Boston, MA 02215 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIH, Mol Toxicol Res Lab,Ctr Environm Hlth, 1400 Lynch St,Box 18540, Jackson, MS 39217 USA. EM anthony.c.skipper@gmail.com; jnsims@bidmc.harvard.edu; clement.yedjou@jsums.edu; paul.b.tchounwou@jsums.edu FU National Institutes of Health through the RCMI-Center for Environmental Health at Jackson State University [NIH/NIMHD-G12MD007581]; Mississippi INBRE grant [NIH/NIGMS-P20GM103476] FX The research described in this publication was made possible in part by a grant from the National Institutes of Health (NIH/NIMHD-G12MD007581) through the RCMI-Center for Environmental Health at Jackson State University; and in part by the Mississippi INBRE grant (NIH/NIGMS-P20GM103476). NR 62 TC 2 Z9 2 U1 3 U2 7 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD JAN PY 2016 VL 13 IS 1 AR 88 DI 10.3390/ijerph13010088 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA DJ4OO UT WOS:000374186100009 ER PT J AU Yedjou, CG Tchounwou, HM Tchounwou, PB AF Yedjou, Clement G. Tchounwou, Hervey M. Tchounwou, Paul B. TI DNA Damage, Cell Cycle Arrest, and Apoptosis Induction Caused by Lead in Human Leukemia Cells SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE lead nitrate; HL-60 cells; DNA damage; apoptosis; cell cycle; cellometer vision ID CARCINOMA HEPG(2) CELLS; ARSENIC TRIOXIDE; HL-60 CELLS; INDUCED CYTOTOXICITY; OXIDATIVE STRESS; COMET ASSAY; IN-VITRO; MECHANISMS; EXPOSURE; DEATH AB In recent years, the industrial use of lead has been significantly reduced from paints and ceramic products, caulking, and pipe solder. Despite this progress, lead exposure continues to be a significant public health concern. The main goal of this research was to determine the in vitro mechanisms of lead nitrate [Pb(NO3)(2)] to induce DNA damage, apoptosis, and cell cycle arrest in human leukemia (HL-60) cells. To reach our goal, HL-60 cells were treated with different concentrations of Pb(NO3)(2) for 24 h. Live cells and necrotic death cells were measured by the propidium idiode (PI) assay using the cellometer vision. Cell apoptosis was measured by the flow cytometry and DNA laddering. Cell cycle analysis was evaluated by the flow cytometry. The result of the PI demonstrated a significant (p < 0.05) increase of necrotic cell death in Pb(NO3)(2)-treated cells, indicative of membrane rupture by Pb(NO3)(2) compared to the control. Data generated from the comet assay indicated a concentration-dependent increase in DNA damage, showing a significant increase (p < 0.05) in comet tail-length and percentages of DNA cleavage. Data generated from the flow cytometry assessment indicated that Pb(NO3)(2) exposure significantly (p < 0.05) increased the proportion of caspase-3 positive cells (apoptotic cells) compared to the control. The flow cytometry assessment also indicated Pb(NO3)(2) exposure caused cell cycle arrest at the G(0)/G(1) checkpoint. The result of DNA laddering assay showed presence of DNA smear in the agarose gel with little presence of DNA fragments in the treated cells compared to the control. In summary, Pb(NO3)(2) inhibits HL-60 cells proliferation by not only inducing DNA damage and cell cycle arrest at the G(0)/G(1) checkpoint but also triggering the apoptosis through caspase-3 activation and nucleosomal DNA fragmentation accompanied by secondary necrosis. We believe that our study provides a new insight into the mechanisms of Pb(NO3)(2) exposure and its associated adverse health effects. C1 [Yedjou, Clement G.; Tchounwou, Hervey M.; Tchounwou, Paul B.] Jackson State Univ, Coll Sci Engn & Technol, NIH, Ctr Environm Hlth,Nat Chemotherapeut Res Lab, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. RP Yedjou, CG (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIH, Ctr Environm Hlth,Nat Chemotherapeut Res Lab, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. EM clement.yedjou@jsums.edu; hervey.tchounwou@students.jsums.edu; paul.b.tchounwou@jsums.edu FU National Institute of General Medical Sciences of the National Institutes of Health [P20GM103476]; National Institutes of Health through the RCMI-Center for Environmental Health at Jackson State University [NIMHD-G12MD007581] FX The research described in this publication was made possible in part by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103476 and in part by a grant from the National Institutes of Health (NIMHD-G12MD007581) through the RCMI-Center for Environmental Health at Jackson State University. NR 47 TC 1 Z9 1 U1 5 U2 6 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD JAN PY 2016 VL 13 IS 1 AR 56 DI 10.3390/ijerph13010056 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA DJ4OO UT WOS:000374186100095 ER PT J AU Zhang, T Du, J Yin, XY Xue, FZ Liu, YX Li, RZ Luo, C Li, L Li, XJ AF Zhang, Tao Du, Jian Yin, Xiaoyan Xue, Fuzhong Liu, Yanxun Li, Runzi Luo, Cheng Li, Liang Li, Xiujun TI Adverse Events in Treating Smear-Positive Tuberculosis Patients in China SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE adverse events; tuberculosis epidemiology; risk factors; China ID 1ST-LINE ANTITUBERCULOSIS DRUGS; INDUCED HEPATOTOXICITY; RISK-FACTORS; PYRAZINAMIDE; RIFAMPIN; THERAPY; SMOKING; SUSCEPTIBILITY; EXPOSURE; COHORT AB This study aimed to estimate the adverse events (AE) rate during anti-tuberculosis treatment and to explore AE-related risk factors. New and previously treated smear-positive tuberculosis (TB) cases were enrolled from eight regions in China between April 2009 and October 2010. The AE rate was estimated, and AE risk factors during anti-TB treatment were assessed using Cox proportional models. Among 2091 Chinese subjects with anti-TB treatment, 462 (22.1%, 95% confidence interval (CI), 20.3-23.9) patients developed AE, with liver injury and gastrointestinal reactions constituting the most common AE. Specifically, 9.8% (95% CI, 8.5-11.1) and 6.3% (95% CI, 5.3-7.4) developed liver injuries and gastrointestinal reactions, respectively. We found that AE rate differed by regions, TB knowledge score, symptoms score and smoking status. Liver injuries were associated with age, sex and smoking status; gastrointestinal reactions were associated with education level and symptom score. Improving patients' knowledge on TB could reduce AE rate. C1 [Zhang, Tao; Xue, Fuzhong; Liu, Yanxun; Li, Runzi; Luo, Cheng; Li, Xiujun] Shandong Univ, Sch Publ Hlth, Dept Biostat, Jinan 250012, Peoples R China. [Du, Jian; Li, Liang] Beijing TB & Thorac Tumor Res Inst, Clin Ctr Off, Beijing 101149, Peoples R China. [Du, Jian; Li, Liang] Capital Med Univ, Beijing Chest Hosp, Beijing 101149, Peoples R China. [Yin, Xiaoyan] NHLBI, Framingham, MA 01702 USA. [Yin, Xiaoyan] Boston Univ Framingham Heart Study, Framingham, MA 01702 USA. RP Li, XJ (reprint author), Shandong Univ, Sch Publ Hlth, Dept Biostat, Jinan 250012, Peoples R China. EM tao_zhang@live.com; jdu-sdu@163.com; xyin@bu.edu; xuefzh@sdu.edu.cn; liu-yx@sdu.edu.cn; runzi_li@hotmail.com; luomadcheng@vip.163.com; liliang@tb123.org; xjli@sdu.edu.cn FU Shandong Provincial Science and Technology Development Program [2014GGH218019]; National Key Technology Support Program [2014BAI13B02]; State Key Laboratory of Pathogen and Biosecurity (Academy of Military Medical Science) [SKLPBS1453] FX This work was supported by Shandong Provincial Science and Technology Development Program (No. 2014GGH218019), the National Key Technology Support Program (No. 2014BAI13B02), and funded by the State Key Laboratory of Pathogen and Biosecurity (Academy of Military Medical Science) (No. SKLPBS1453). We are grateful to Kequan Zhou for language editing. We also acknowledge the invaluable contributions made by Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Shanghai Municipal Center for Disease Control, Tianjin Center for Disease Control and Prevention, Henan Provincial Center for Disease Prevention and Control Center, Hebei Provincial Center for Disease Prevention and Control Center, Guangxi Center for Disease Control and Prevention, Guangzhou Chest Hospital, Chongqing Institute for Tuberculosis Control and Prevention, and Yunnan Provincial Center for Tuberculosis Prevention and Control. NR 41 TC 0 Z9 0 U1 1 U2 2 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD JAN PY 2016 VL 13 IS 1 AR 86 DI 10.3390/ijerph13010086 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA DJ4OO UT WOS:000374186100014 ER PT J AU Sheliga, BM Quaia, C FitzGibbon, EJ Cumming, BG AF Sheliga, Boris M. Quaia, Christian FitzGibbon, Edmond J. Cumming, Bruce G. TI Ocular-following responses to white noise stimuli in humans reveal a novel nonlinearity that results from temporal sampling SO JOURNAL OF VISION LA English DT Article DE visual motion; visual flicker; speed tuning; broadband visual stimuli ID TRACKING EYE-MOVEMENTS; CORTICAL AREAS MT; VISUAL-CORTEX; SPATIAL SUMMATION; MACAQUE; MOTION; SPEED; PERCEPTION; NEURONS; REPRESENTATION AB White noise stimuli are frequently used to study the visual processing of broadband images in the laboratory. A common goal is to describe how responses are derived from Fourier components in the image. We investigated this issue by recording the ocular-following responses (OFRs) to white noise stimuli in human subjects. For a given speed we compared OFRs to unfiltered white noise with those to noise filtered with band-pass filters and notch filters. Removing components with low spatial frequency (SF) reduced OFR magnitudes, and the SF associated with the greatest reduction matched the SF that produced the maximal response when presented alone. This reduction declined rapidly with SF, compatible with a winner-take-all operation. Removing higher SF components increased OFR magnitudes. For higher speeds this effect became larger and propagated toward lower SFs. All of these effects were quantitatively well described by a model that combined two factors: (a) an excitatory drive that reflected the OFRs to individual Fourier components and (b) a suppression by higher SF channels where the temporal sampling of the display led to flicker. This nonlinear interaction has an important practical implication: Even with high refresh rates (150 Hz), the temporal sampling introduced by visual displays has a significant impact on visual processing. For instance, we show that this distorts speed tuning curves, shifting the peak to lower speeds. Careful attention to spectral content, in the light of this nonlinearity, is necessary to minimize the resulting artifact when using white noise patterns undergoing apparent motion. C1 [Sheliga, Boris M.; Quaia, Christian; FitzGibbon, Edmond J.; Cumming, Bruce G.] NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Sheliga, BM (reprint author), NIH, Sensorimotor Res Lab, Bldg 10, Bethesda, MD 20892 USA. EM bms@nei.nih.gov FU National Eye Institute at the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Eye Institute at the National Institutes of Health. NR 36 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PD JAN PY 2016 VL 16 IS 1 AR 8 DI 10.1167/16.1.8 PG 22 WC Ophthalmology SC Ophthalmology GA DJ4KP UT WOS:000374174300008 PM 26762277 ER PT J AU David, JM Hamilton, DH Palena, C AF David, Justin M. Hamilton, Duane H. Palena, Claudia TI MUC1 upregulation promotes immune resistance in tumor cells undergoing brachyury-mediated epithelial-mesenchymal transition SO ONCOIMMUNOLOGY LA English DT Article DE Brachyury; EMT; immune resistance; MUC1 ID TRANSCRIPTION FACTOR BRACHYURY; HUMAN CARCINOMA-CELLS; LUNG-CANCER CELLS; 1 ONCOPROTEIN; COLON-CANCER; BREAST; METASTASIS; EXPRESSION; VACCINE; APOPTOSIS AB Epithelial-mesenchymal transition (EMT) is a molecular and cellular program in which epithelial cells lose their well-differentiated phenotype and adopt mesenchymal characteristics. This process, which occurs naturally during embryogenesis, has also been shown to be associated with cancer progression and with tumor recurrence following conventional therapies. Brachyury is a transcription factor that mediates EMT during development, and is aberrantly expressed in various human cancers where it promotes tumor cell EMT, metastatic dissemination, and resistance to conventional therapies. We have recently shown that very high expression of brachyury can protect tumor cells against immune cell-mediated cytotoxicity. In seeking to elucidate mechanisms of immunotherapy resistance, we have discovered a novel positive association between brachyury and mucin-1 (MUC1). MUC1 is overexpressed in the majority of carcinomas, and it has been shown to mediate oncogenic signaling and confer resistance to genotoxic agents. We found that MUC1 is concomitantly upregulated in tumor cell lines that highly express brachyury due to an enhancement of MUC1 mRNA stability. Analysis of patient lung tumor tissues also identified a positive association between these two proteins in the majority of samples. Inhibition of MUC1 by siRNA-based gene silencing markedly enhanced the susceptibility of brachyury-expressing cancer cells to killing by tumor necrosis-related apoptosis-inducing ligand (TRAIL) and to perforin/granzyme-dependent lysis by immune cytotoxic cells. These studies confirm a protective role for MUC1 in brachyury-expressing cancer cells, and suggest that inhibition of MUC1 can restore the susceptibility of mesenchymal-like cancer cells to immune attack. C1 [David, Justin M.; Hamilton, Duane H.; Palena, Claudia] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Palena, C (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM palenac@mail.nih.gov FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 65 TC 3 Z9 3 U1 3 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 4 AR e1117738 DI 10.1080/2162402X.2015.1117738 PG 12 WC Oncology; Immunology SC Oncology; Immunology GA DJ4RE UT WOS:000374194200031 ER PT J AU Gulley, JL Mulders, P Albers, P Banchereau, J Bolla, M Pantel, K Powles, T AF Gulley, James L. Mulders, Peter Albers, Peter Banchereau, Jacques Bolla, Michel Pantel, Klaus Powles, Thomas TI Perspectives on sipuleucel-T: Its role in the prostate cancer treatment paradigm SO ONCOIMMUNOLOGY LA English DT Review DE Clinical trials; immune responses; immunotherapy; prostate cancer; sipuleucel-T ID AUTOLOGOUS CELLULAR IMMUNOTHERAPY; DENDRITIC CELLS; THERAPEUTIC VACCINES; INCREASED SURVIVAL; PLUS PREDNISONE; CLINICAL-TRIALS; IMPACT TRIAL; DOUBLE-BLIND; LEUKAPHERESIS; DONORS AB Sipuleucel-T is an autologous cellular immunotherapy approved in the US for patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). This significant advance for mCRPC treatment provides healthcare professionals with another effective therapy to extend survival. As an immunotherapy, sipuleucel-T possesses specific characteristics differentiating it from traditional therapies. At a roundtable meeting of experts, sipuleucel-T data were discussed, focusing on interpretation and clinical implications. Important differences between immunotherapies and traditional therapies were explored, e.g., mode of action, outcomes, data consistency and robustness, timing of sipuleucel-T treatment, and future perspectives in areas such as short-term markers of long-term benefit. C1 [Gulley, James L.] NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA. [Gulley, James L.] NCI, Tumor Immunol & Biol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. [Mulders, Peter] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Albers, Peter] Univ Dusseldorf, Fac Med, Dusseldorf, Germany. [Banchereau, Jacques] Jackson Lab Genom Med, Farmington, CT USA. [Bolla, Michel] CHU Grenoble, Dept Radiat Therapy, F-38043 Grenoble, France. [Pantel, Klaus] Univ Med Ctr Hamburg Eppendorf, Dept Tumor Biol, Hamburg, Germany. [Powles, Thomas] Queen Mary Univ London, Barts Canc Inst, London, England. RP Gulley, JL (reprint author), NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.; Gulley, JL (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Dendreon Pharmaceuticals Inc. FX This article describes data that were discussed by the authors at a roundtable meeting supported by Dendreon Pharmaceuticals Inc. We thank Stuart Langley and Joanne Swainston of Gardiner-Caldwell Communications (Macclesfield, UK) for medical writing and coordination support, which was funded by Dendreon Pharmaceuticals Inc. NR 49 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 4 AR e1107698 DI 10.1080/2162402X.2015.1107698 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA DJ4RE UT WOS:000374194200023 PM 27141392 ER PT J AU Turkbey, B Lindenberg, ML Adler, S Kurdziel, KA McKinney, YL Weaver, J Vocke, CD Anver, M Bratslavsky, G Eclarinal, P Kwarteng, G Lin, FI Yaqub-Ogun, N Merino, MJ Linehan, WM Choyke, PL Metwalli, AR AF Turkbey, Baris Lindenberg, Maria L. Adler, Stephen Kurdziel, Karen A. McKinney, Yolanda L. Weaver, Juanita Vocke, Cathy D. Anver, Miriam Bratslavsky, Gennady Eclarinal, Philip Kwarteng, Gideon Lin, Frank I. Yaqub-Ogun, Nana Merino, Maria J. Linehan, W. Marston Choyke, Peter L. Metwalli, Adam R. TI PET/CT imaging of renal cell carcinoma with F-18-VM4-037: a phase II pilot study SO ABDOMINAL RADIOLOGY LA English DT Article DE Renal cell carcinoma; Carbonic anhydrase IX; 18F-VM4-037; Positron emission tomography (PET) ID CARBONIC-ANHYDRASE-IX; VHL GENE MUTATION; INDEPENDENT PREDICTOR; CANCER; EXPRESSION; TUMORS; RADIOIMMUNOTHERAPY; GIRENTUXIMAB; SURVIVAL; CAIX AB Background: Carbonic anhydrase IX (CA-IX) is a potential imaging biomarker of clear cell renal cell carcinoma (ccRCC). Here, we report the results of a phase II clinical trial of a small molecule radiotracer targeting CA-IX (F-18-VM4-037) in ccRCC. Methods: Between October 2012 and May 2013, 11 patients with kidney masses underwent F-18-VM4-037 PET/CT prior to surgery. Dynamic imaging was performed for the first 45 min post injection and whole-body imaging was obtained at 60 min post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging. Results: All patients tolerated the radiotracer well with no adverse events. Ten of the 11 patients had histologically confirmed malignancy. One patient had a Bosniak Type 3 cyst with no tumor found at surgery. Two patients had extrarenal disease and 9 had tumors only in the kidney. Primary ccRCC lesions were difficult to visualize on PET alone due to high uptake of the tracer in the adjacent normal kidney parenchyma, however when viewed in conjunction with CT, the tumors were easily localized. Metastatic lesions were clearly visible on PET. Mean SUV for primary kidney lesions was 2.55 in all patients; in patients with histologically confirmed ccRCC, the mean SUV was 3.16. The time-activity curves (TAC) are consistent with reversible ligand binding with peak activity concentration at 8 min post injection followed by washout. Distribution Volume Ratio (DVR) of the lesions was measured using the Logan graphical analysis method. The mean DVR value across the 9 kidney lesions was 5.2 +/- 2.8, (range 0.68-10.34). Conclusion: 18F-VM4-037 is a well-tolerated PET agent that allows same day imaging of CA-IX expression. The agent demonstrated moderate signal uptake in primary tumors and excellent visualization of CA-IX positive metastases. While the evaluation of primary ccRCC lesions is challenging due to high background activity in the normal kidney parenchyma, 18F-VM4-037 may be most useful in the evaluation of metastatic ccRCC lesions. C1 [Turkbey, Baris; Lindenberg, Maria L.; Kurdziel, Karen A.; McKinney, Yolanda L.; Lin, Frank I.; Choyke, Peter L.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. [Adler, Stephen; Weaver, Juanita; Anver, Miriam; Eclarinal, Philip; Kwarteng, Gideon] Leidos Biomed Res Inc, Clin Res Directorate, CMRP, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Vocke, Cathy D.; Yaqub-Ogun, Nana; Linehan, W. Marston; Metwalli, Adam R.] NCI, Urol Oncol Branch, NIH, Bldg 10,Room 2 W-5940,10 Ctr Dr,MSC 1210, Bethesda, MD 20892 USA. [Bratslavsky, Gennady] SUNY Upstate, Dept Urol, Syracuse, NY USA. [Lin, Frank I.] NCI, Canc Imaging Program, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA. RP Turkbey, B (reprint author), NCI, Mol Imaging Program, Bethesda, MD 20892 USA. EM turkbeyi@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract 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. This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Special thanks to the Urologic Oncology Fellows of the Urologic Oncology Branch of the National Cancer Institute, NIH; Avi Rosenberg, MD, PhD, Laboratory of Pathology, National Cancer Institute, NIH; Hartmut Kolb from Siemens and PET/NET for supplying the agent. NR 23 TC 4 Z9 4 U1 7 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2366-004X EI 2366-0058 J9 ABDOM RADIOL JI Abdom. Radiol. PD JAN PY 2016 VL 41 IS 1 BP 109 EP 118 DI 10.1007/s00261-015-0599-1 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DJ3MK UT WOS:000374109400014 PM 26830617 ER PT J AU Nathan, N Burke, K Trickett, C Moss, J Darling, TN AF Nathan, Neera Burke, Kristina Trickett, Cory Moss, Joel Darling, Thomas N. TI The Adult Phenotype of Tuberous Sclerosis Complex SO ACTA DERMATO-VENEREOLOGICA LA English DT Editorial Material ID CONSENSUS CONFERENCE; RECOMMENDATIONS; PREVALENCE C1 [Nathan, Neera; Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. [Nathan, Neera; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Burke, Kristina] Madigan Army Med Ctr, Dept Dermatol, Tacoma, WA 98431 USA. [Trickett, Cory] Blanchfield Army Community Hosp, Dept Dermatol, Ft Campbell, KY USA. RP Darling, TN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. EM thomas.darling@usuhs.edu OI Darling, Thomas/0000-0002-5161-1974 FU Intramural NIH HHS NR 14 TC 2 Z9 2 U1 0 U2 0 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 EI 1651-2057 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2016 VL 96 IS 2 BP 278 EP + DI 10.2340/00015555-2203 PG 3 WC Dermatology SC Dermatology GA DJ1DO UT WOS:000373943700035 PM 26258325 ER PT J AU Nathan, N Burke, K Trickett, C Moss, J Darling, TN AF Nathan, Neera Burke, Kristina Trickett, Cory Moss, Joel Darling, Thomas N. TI The Adult Phenotype of Tuberous Sclerosis Complex SO ACTA DERMATO-VENEREOLOGICA LA English DT Editorial Material ID CONSENSUS CONFERENCE; RECOMMENDATIONS; PREVALENCE C1 [Nathan, Neera; Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. [Nathan, Neera; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Burke, Kristina] Madigan Army Med Ctr, Dept Dermatol, Tacoma, WA 98431 USA. [Trickett, Cory] Blanchfield Army Community Hosp, Dept Dermatol, Ft Campbell, KY USA. RP Darling, TN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. EM thomas.darling@usuhs.edu NR 14 TC 0 Z9 0 U1 0 U2 0 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 EI 1651-2057 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2016 VL 96 IS 2 PG 3 WC Dermatology SC Dermatology GA DJ1DO UT WOS:000373943700036 ER PT J AU Fu, WQ Khraiwesh, B Liu, HB Kai, L AF Fu, Weiqi Khraiwesh, Basel Liu, Hongbing Kai, Lei TI Advances in Biotechnology for Sustainable Development SO BIOMED RESEARCH INTERNATIONAL LA English DT Editorial Material C1 [Fu, Weiqi; Khraiwesh, Basel] New York Univ Abu Dhabi, Div Sci & Math, POB 129188, Abu Dhabi, U Arab Emirates. [Fu, Weiqi; Khraiwesh, Basel] New York Univ Abu Dhabi, CGSB, POB 129188, Abu Dhabi, U Arab Emirates. [Fu, Weiqi] Univ Iceland, Ctr Syst Biol, Sch Engn & Nat Sci, IS-101 Reykjavik, Iceland. [Fu, Weiqi] Univ Iceland, Fac Ind Engn Mech Engn & Comp Sci, Sch Engn & Nat Sci, IS-101 Reykjavik, Iceland. [Liu, Hongbing] NIDDK, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Kai, Lei] Max Planck Inst Biochem, Klopferspitz 18A, D-82152 Martinsried, Germany. RP Fu, WQ (reprint author), New York Univ Abu Dhabi, Div Sci & Math, POB 129188, Abu Dhabi, U Arab Emirates.; Fu, WQ (reprint author), New York Univ Abu Dhabi, CGSB, POB 129188, Abu Dhabi, U Arab Emirates.; Fu, WQ (reprint author), Univ Iceland, Ctr Syst Biol, Sch Engn & Nat Sci, IS-101 Reykjavik, Iceland.; Fu, WQ (reprint author), Univ Iceland, Fac Ind Engn Mech Engn & Comp Sci, Sch Engn & Nat Sci, IS-101 Reykjavik, Iceland. EM wf21@nyu.edu OI Fu, Weiqi/0000-0002-7368-383X NR 0 TC 0 Z9 0 U1 1 U2 5 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2016 AR 7154916 DI 10.1155/2016/7154916 PG 2 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA DJ3EL UT WOS:000374087500001 ER PT J AU Brychta, RJ Arnardottir, NY Johannsson, E Wright, EC Eiriksdottir, G Gudnason, V Marinac, CR Davis, M Koster, A Caserotti, P Sveinsson, T Harris, T Chen, KY AF Brychta, Robert J. Arnardottir, Nanna Yr Johannsson, Erlingur Wright, Elizabeth C. Eiriksdottir, Gudny Gudnason, Vilmundur Marinac, Catherine R. Davis, Megan Koster, Annemarie Caserotti, Paolo Sveinsson, Thorarinn Harris, Tamara Chen, Kong Y. TI Influence of Day Length and Physical Activity on Sleep Patterns in Older Icelandic Men and Women SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE aging; seasonal; total sleep time; physical activity; accelerometer ID GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK; LIGHT EXPOSURE; OSTEOPOROTIC FRACTURES; MONOCHROMATIC LIGHT; SEASONAL-VARIATIONS; ELDERLY PERSONS; UNITED-STATES; BLUE-LIGHT; POOR SLEEP; AGE AB Study Objectives: To identify cross-sectional and seasonal patterns of sleep and physical activity (PA) in community-dwelling, older Icelandic adults using accelerometers. Methods: A seven-day free-living protocol of 244 (110 female) adults aged 79.7 +/- 4.9 years was conducted as part of a larger population-based longitudinal observational-cohort study in the greater Reykjavik area of Iceland. A subpopulation (n = 72) repeated the 7-day measurement during seasonal periods with greater (13.4 +/- 1.4 h) and lesser (7.7 +/- 1.8 h) daylight. Results: Cross-sectional analyses using multiple linear regression models revealed that day length was a significant independent predictor of sleep duration, mid-sleep, and rise time (all p < 0.05). However, the actual within-individual differences in sleep patterns of the repeaters were rather subtle between periods of longer and shorter day-lengths. Compared to women, men had a shorter sleep duration (462 +/- 80 vs. 487 +/- 68 minutes, p = 0.008), earlier rise time, and a greater number of awakenings per night (46.5 +/- 18.3 vs. 40.2 +/- 15.7, p = 0.007), but sleep efficiency and onset latency were similar between the two sexes. Daily PA was also similar between men and women and between periods of longer and shorter day-lengths. BMI, age, gender, and overall PA all contributed to the variations in sleep parameters using multiple regression analysis. Conclusions: The sleep and PA characteristics of this unique population revealed some gender differences, but there was limited variation in response to significant daylight changes which may be due to long-term adaptation. C1 [Brychta, Robert J.; Wright, Elizabeth C.; Marinac, Catherine R.; Davis, Megan; Chen, Kong Y.] NIDDK, Bethesda, MD 20892 USA. [Arnardottir, Nanna Yr; Sveinsson, Thorarinn] Univ Iceland, Res Ctr Movement Sci, Reykjavik, Iceland. [Arnardottir, Nanna Yr; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Johannsson, Erlingur] Univ Iceland, Sch Educ, Ctr Sport & Hlth Sci, Laugarvatn, Iceland. [Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Koster, Annemarie] Maastricht Univ, Dept Social Med, CAPHRI Sch Publ Hlth & Primary Care, NL-6200 MD Maastricht, Netherlands. [Caserotti, Paolo] Univ Southern Denmark, Dept Sports Sci & Clin Biomech, Aarhus, Denmark. [Harris, Tamara] NIA, Bethesda, MD 20892 USA. RP Brychta, RJ (reprint author), NIH, 10 Ctr Dr,Bldg 10,Rm 5-5750, Bethesda, MD USA. EM brychtar@niddk.nih.gov RI Sveinsson, Thorarinn/F-7554-2010; OI Sveinsson, Thorarinn/0000-0001-8989-5514; Chen, Kong/0000-0002-0306-1904 FU National Institutes of Health (NIH) [N01-AG-1-2100]; National Institute on Aging (NIA) Intramural Research Program; Hjartavernd (Icelandic Heart Association); Althingi (the Icelandic Parliament); National Institutes of Health Intramural Research Program [Z01 DK071013, Z01 DK071014] FX This was not an industry supported study. This study was funded by National Institutes of Health (NIH) contract N01-AG-1-2100, the National Institute on Aging (NIA) Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). This study was also supported by National Institutes of Health Intramural Research Program contract number: Z01 DK071013 and Z01 DK071014 for R.J.B. and K.Y.C. The authors have indicated no financial conflicts of interest. NR 44 TC 0 Z9 0 U1 3 U2 8 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2016 VL 12 IS 2 BP 203 EP 213 AR PII jc-00215-15 DI 10.5664/jcsm.5486 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA DJ3XB UT WOS:000374138900009 PM 26414978 ER PT J AU Drame, PM Meng, ZJ Bennuru, S Herrick, JA Veenstra, TD Nutman, TB AF Drame, Papa M. Meng, Zhaojing Bennuru, Sasisekhar Herrick, Jesica A. Veenstra, Timothy D. Nutman, Thomas B. TI Identification and Validation of Loa loa Microfilaria-Specific Biomarkers: a Rational Design Approach Using Proteomics and Novel Immunoassays SO MBIO LA English DT Article ID MASS TREATMENT; HUMAN URINE; LOIASIS; INFECTION; ALBENDAZOLE; IVERMECTIN; ANTIBODIES; ANTIGEN; ONCHOCERCIASIS; DISCOVERY AB Immunoassays are currently needed to quantify Loa loa microfilariae (mf). To address this need, we have conducted proteomic and bioinformatic analyses of proteins present in the urine of a Loa mf-infected patient and used this information to identify putative biomarkers produced by L. loa mf. In total, 70 of the 15,444 described putative L. loa proteins were identified. Of these 70, 18 were L. loa mf specific, and 2 of these 18 (LOAG_16297 and LOAG_17808) were biologically immunogenic. We developed novel reverse luciferase immunoprecipitation system (LIPS) immunoassays to quantify these 2 proteins in individual plasma samples. Levels of these 2 proteins in microfilaremic L. loa-infected patients were positively correlated to mf densities in the corresponding blood samples (r = 0.71 and P < 0.0001 for LOAG_16297 and r = 0.61 and P = 0.0002 for LOAG_17808). For LOAG_16297, the levels in plasma were significantly higher in Loa-infected (geometric mean [GM], 0.045 mu g/ml) than in uninfected (P < 0.0001), Wuchereria bancrofti-infected (P = 0.0005), and Onchocerca volvulus-infected (P < 0.0001) individuals, whereas for LOAG_17808 protein, they were not significantly different between Loa-infected (GM, 0.123 mu g/ml) and uninfected (P = 0.06) and W. bancrofti-infected (P = 0.32) individuals. Moreover, only LOAG_16297 showed clear discriminative ability between L. loa and the other potentially coendemic filariae. Indeed, the specificity of the LOAG_16297 reverse LIPS assay was 96% (with a sensitivity of 77%). Thus, LOAG_16297 is a very promising biomarker that will be exploited in a quantitative point-of-care immunoassay for determination of L. loa mf densities. IMPORTANCE Loa loa, the causative agent of loiasis, is a parasitic nematode transmitted to humans by the tabanid Chrysops fly. Some individuals infected with L. loa microfilariae (mf) in high densities are known to experience post-ivermectin severe adverse events (SAEs [encephalopathy, coma, or death]). Thus, ivermectin-based mass drug administration (MDA) programs for onchocerciasis and for lymphatic filariasis control have been interrupted in parts of Africa where these filarial infections coexist with L. loa. To allow for implementation of MDA for onchocerciasis and lymphatic filariasis, tools that can accurately identify people at risk of developing post-ivermectin SAEs are needed. Our study, using host-based proteomics in combination with novel immunoassays, identified a single Loa-specific antigen (LOAG_16297) that can be used as a biomarker for the prediction of L. loa mf levels in the blood of infected patients. Therefore, the use of such biomarker could be important in the point-of-care assessment of L. loa mf densities. C1 [Drame, Papa M.; Bennuru, Sasisekhar; Herrick, Jesica A.; Nutman, Thomas B.] NIAID, NIH, Helminth Immunol Sect, Parasit Dis Lab, Bldg 10, Bethesda, MD 20892 USA. [Meng, Zhaojing; Veenstra, Timothy D.] Leidos Inc, Frederick Natl Lab Canc Res, Prot Characterizat Lab, Frederick, MD USA. [Herrick, Jesica A.] Univ Illinois, Dept Med, Div Infect Dis Immunol & Int Med, Chicago, IL USA. [Veenstra, Timothy D.] Maranatha Baptist Univ, Dept Appl Sci, Watertown, WI USA. RP Nutman, TB (reprint author), NIAID, NIH, Helminth Immunol Sect, Parasit Dis Lab, Bldg 10, Bethesda, MD 20892 USA. EM tnutman@niaid.nih.gov FU Division of Intramural Research (DIR) of the National Institute of Allergy and Infectious Diseases FX This study was funded by the Division of Intramural Research (DIR) of the National Institute of Allergy and Infectious Diseases. The funder had no role in study design, data collection and interpretation, or decision to submit the work for publication. NR 36 TC 1 Z9 1 U1 3 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2016 VL 7 IS 1 AR e02132-15 DI 10.1128/mBio.02132-15 PG 8 WC Microbiology SC Microbiology GA DJ0ZO UT WOS:000373933100019 PM 26884435 ER PT J AU Kristie, TM AF Kristie, Thomas M. TI Chromatin Modulation of Herpesvirus Lytic Gene Expression: Managing Nucleosome Density and Heterochromatic Histone Modifications SO MBIO LA English DT Editorial Material ID VIRAL-DNA; INFECTION; BLOCKS; REPLICATION; COMPONENTS; INHIBITOR; LYMPHOMA; PROMOTES; COMPLEX; CELLS AB Like their cellular hosts, herpesviruses are subject to the regulatory impacts of chromatin assembled on their genomes. Upon infection, these viruses are assembled into domains of chromatin with heterochromatic signatures that suppress viral gene expression or euchromatic characteristics that promote gene expression. The organization and modulation of these chromatin domains appear to be intimately linked to the coordinated expression of the different classes of viral genes and thus ultimately play an important role in the progression of productive infection or the establishment and maintenance of viral latency. A recent report from the Knipe laboratory (J. S. Lee, P. Raja, and D. M. Knipe, mBio 7: e02007-15, 2016) contributes to the understanding of the dynamic modulation of chromatin assembled on the herpes simplex virus genome by monitoring the levels of characteristic heterochromatic histone modifications (histone H3 lysine 9 and 27 methylation) associated with a model viral early gene during the progression of lytic infection. Additionally, this study builds upon previous observations that the viral immediate-early protein ICP0 plays a role in reducing the levels of heterochromatin associated with the early genes. C1 [Kristie, Thomas M.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Kristie, TM (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM tkristie@niaid.hih.gov NR 19 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2016 VL 7 IS 1 AR e00098-16 DI 10.1128/mBio.00098-16 PG 3 WC Microbiology SC Microbiology GA DJ0ZO UT WOS:000373933100040 PM 26884430 ER PT J AU Panackal, AA Williamson, KC van de Beek, D Boulware, DR Williamson, PR AF Panackal, Anil A. Williamson, Kim C. van de Beek, Diederik Boulware, David R. Williamson, Peter R. TI Fighting the Monster: Applying the Host Damage Framework to Human Central Nervous System Infections SO MBIO LA English DT Article ID RECONSTITUTION INFLAMMATORY SYNDROME; PROGRESSIVE MULTIPLE-SCLEROSIS; RANDOMIZED CONTROLLED-TRIAL; SEVERE FALCIPARUM-MALARIA; BRAIN ENDOTHELIAL-CELLS; NITRIC-OXIDE PRODUCTION; HUMAN CEREBRAL MALARIA; CRYPTOCOCCAL MENINGITIS; TUBERCULOUS MENINGITIS; CEREBROSPINAL-FLUID AB The host damage-response framework states that microbial pathogenesis is a product of microbial virulence factors and collateral damage from host immune responses. Immune-mediated host damage is particularly important within the size-restricted central nervous system (CNS), where immune responses may exacerbate cerebral edema and neurological damage, leading to coma and death. In this review, we compare human host and therapeutic responses in representative nonviral generalized CNS infections that induce archetypal host damage responses: cryptococcal menigoencephalitis and tuberculous meningitis in HIV-infected and non-HIV-infected patients, pneumococcal meningitis, and cerebral malaria. Consideration of the underlying patterns of host responses provides critical insights into host damage and may suggest tailored adjunctive therapeutics to improve disease outcome. C1 [Panackal, Anil A.; Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Williamson, Kim C.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [van de Beek, Diederik] Univ Amsterdam, Acad Med Ctr, Dept Neurol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Boulware, David R.] Univ Minnesota, Dept Med, Div Infect Dis & Int Med, Minneapolis, MN USA. RP Williamson, PR (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM williamsonpr@mail.nih.gov OI Boulware, David/0000-0002-4715-0060 FU National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH) FX This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH). NR 153 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2016 VL 7 IS 1 AR e01906-15 DI 10.1128/mBio.01906-15 PG 13 WC Microbiology SC Microbiology GA DJ0ZO UT WOS:000373933100052 PM 26814182 ER PT J AU Tsai, YC Conlan, S Deming, C Segre, JA Kong, HH Korlach, J Oh, J AF Tsai, Yu-Chih Conlan, Sean Deming, Clayton Segre, Julia A. Kong, Heidi H. Korlach, Jonas Oh, Julia CA NISC Comparative Sequencing Progra TI Resolving the Complexity of Human Skin Metagenomes Using Single-Molecule Sequencing SO MBIO LA English DT Article ID GENOME ASSEMBLIES; ANNOTATION; ALGORITHMS; DIVERSITY; ALIGNMENT; COVERAGE; BACTERIA; RARE; TOOL AB Deep metagenomic shotgun sequencing has emerged as a powerful tool to interrogate composition and function of complex microbial communities. Computational approaches to assemble genome fragments have been demonstrated to be an effective tool for de novo reconstruction of genomes from these communities. However, the resultant "genomes" are typically fragmented and incomplete due to the limited ability of short-read sequence data to assemble complex or low-coverage regions. Here, we use single-molecule, real-time (SMRT) sequencing to reconstruct a high-quality, closed genome of a previously uncharacterized Corynebacterium simulans and its companion bacteriophage from a skin metagenomic sample. Considerable improvement in assembly quality occurs in hybrid approaches incorporating short-read data, with even relatively small amounts of long-read data being sufficient to improve metagenome reconstruction. Using short-read data to evaluate strain variation of this C. simulans in its skin community at single-nucleotide resolution, we observed a dominant C. simulans strain with moderate allelic heterozygosity throughout the population. We demonstrate the utility of SMRT sequencing and hybrid approaches in metagenome quantitation, reconstruction, and annotation. IMPORTANCE The species comprising a microbial community are often difficult to deconvolute due to technical limitations inherent to most short-read sequencing technologies. Here, we leverage new advances in sequencing technology, single-molecule sequencing, to significantly improve reconstruction of a complex human skin microbial community. With this long-read technology, we were able to reconstruct and annotate a closed, high-quality genome of a previously uncharacterized skin species. We demonstrate that hybrid approaches with short-read technology are sufficiently powerful to reconstruct even single-nucleotide polymorphism level variation of species in this a community. C1 [Tsai, Yu-Chih; Korlach, Jonas] Pacific Biosci, Menlo Pk, CA USA. [Conlan, Sean; Deming, Clayton; Segre, Julia A.; Oh, Julia] NHGRI, Translat & Funct Genom Branch, Bethesda, MD 20892 USA. [NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr, Bethesda, MD 20892 USA. [Kong, Heidi H.] NCI, Ctr Canc Res, Dermatol Branch, Bethesda, MD 20892 USA. [Oh, Julia] Jackson Lab Genom Med, Farmington, CT USA. RP Oh, J (reprint author), NHGRI, Translat & Funct Genom Branch, Bethesda, MD 20892 USA. EM julia.oh@jax.org OI Kong, Heidi/0000-0003-4424-064X FU HHS | National Institutes of Health (NIH) FX HHS | National Institutes of Health (NIH) provided funding to Julia Oh, Sean Conlan, Clayton Deming, Julia A. Segre, and Heidi Kong. NR 40 TC 5 Z9 5 U1 3 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2016 VL 7 IS 1 AR e01948-15 DI 10.1128/mBio.01948-15 PG 13 WC Microbiology SC Microbiology GA DJ0ZO UT WOS:000373933100063 PM 26861018 ER PT J AU Wahl-Jensen, V Johnson, JC Lauck, M Weinfurter, JT Moncla, LH Weiler, AM Charlier, O Rojas, O Byrum, R Ragland, DR Huzella, L Zommer, E Cohen, M Bernbaum, JG Cai, YY Sanford, HB Mazur, S Johnson, RF Qin, J Palacios, GF Bailey, AL Jahrling, PB Goldberg, TL O'Connor, DH Friedrich, TC Kuhn, JH AF Wahl-Jensen, Victoria Johnson, Joshua C. Lauck, Michael Weinfurter, Jason T. Moncla, Louise H. Weiler, Andrea M. Charlier, Olivia Rojas, Oscar Byrum, Russell Ragland, Dan R. Huzella, Louis Zommer, Erika Cohen, Melanie Bernbaum, John G. Cai, Yingyun Sanford, Hannah B. Mazur, Steven Johnson, Reed F. Qin, Jing Palacios, Gustavo F. Bailey, Adam L. Jahrling, Peter B. Goldberg, Tony L. O'Connor, David H. Friedrich, Thomas C. Kuhn, Jens H. TI Divergent Simian Arteriviruses Cause Simian Hemorrhagic Fever of Differing Severities in Macaques SO MBIO LA English DT Article ID ENDOPLASMIC-RETICULUM; HAEMORRHAGIC FEVER; VIRUS; PATHOLOGY; OUTBREAK; DISEASE; AGENT AB Simian hemorrhagic fever (SHF) is a highly lethal disease in captive macaques. Three distinct arteriviruses are known etiological agents of past SHF epizootics, but only one, simian hemorrhagic fever virus (SHFV), has been isolated in cell culture. The natural reservoir(s) of the three viruses have yet to be identified, but African nonhuman primates are suspected. Eleven additional divergent simian arteriviruses have been detected recently in diverse and apparently healthy African cercopithecid monkeys. Here, we report the successful isolation in MARC-145 cell culture of one of these viruses, Kibale red colobus virus 1 (KRCV-1), from serum of a naturally infected red colobus (Procolobus [Piliocolobus] rufomitratus tephrosceles) sampled in Kibale National Park, Uganda. Intramuscular (i.m.) injection of KRCV-1 into four cynomolgus macaques (Macaca fascicularis) resulted in a self-limiting nonlethal disease characterized by depressive behavioral changes, disturbance in coagulation parameters, and liver enzyme elevations. In contrast, i.m. injection of SHFV resulted in typical lethal SHF characterized by mild fever, lethargy, lymphoid depletion, lymphoid and hepatocellular necrosis, low platelet counts, increased liver enzyme concentrations, coagulation abnormalities, and increasing viral loads. As hypothesized based on the genetic and presumed antigenic distance between KRCV-1 and SHFV, all four macaques that had survived KRCV-1 injection died of SHF after subsequent SHFV injection, indicating a lack of protective heterotypic immunity. Our data indicate that SHF is a disease of macaques that in all likelihood can be caused by a number of distinct simian arteriviruses, although with different severity depending on the specific arterivirus involved. Consequently, we recommend that current screening procedures for SHFV in primate-holding facilities be modified to detect all known simian arteriviruses. IMPORTANCE Outbreaks of simian hemorrhagic fever (SHF) have devastated captive Asian macaque colonies in the past. SHF is caused by at least three viruses of the family Arteriviridae: simian hemorrhagic fever virus (SHFV), simian hemorrhagic encephalitis virus (SHEV), and Pebjah virus (PBJV). Nine additional distant relatives of these three viruses were recently discovered in apparently healthy African nonhuman primates. We hypothesized that all simian arteriviruses are potential causes of SHF. To test this hypothesis, we inoculated cynomolgus macaques with a highly divergent simian arterivirus (Kibale red colobus virus 1 [KRCV-1]) from a wild Ugandan red colobus. Despite being only distantly related to red colobuses, all of the macaques developed disease. In contrast to SHFV-infected animals, KRCV-1-infected animals survived after a mild disease presentation. Our study advances the understanding of an important primate disease. Furthermore, our data indicate a need to include the full diversity of simian arteriviruses in nonhuman primate SHF screening assays. C1 [Wahl-Jensen, Victoria; Johnson, Joshua C.; Rojas, Oscar; Byrum, Russell; Ragland, Dan R.; Huzella, Louis; Zommer, Erika; Cohen, Melanie; Bernbaum, John G.; Cai, Yingyun; Sanford, Hannah B.; Mazur, Steven; Jahrling, Peter B.; Kuhn, Jens H.] NIAID, NIH, Integrated Res Facil Ft Detrick, Frederick, MD USA. [Lauck, Michael; Weinfurter, Jason T.; Moncla, Louise H.; Weiler, Andrea M.; Charlier, Olivia; Bailey, Adam L.; Goldberg, Tony L.; O'Connor, David H.; Friedrich, Thomas C.] Univ Wisconsin, Madison, WI USA. [Johnson, Reed F.; Jahrling, Peter B.] NIAID, NIH, Emerging Viral Pathogens Sect, Frederick, MD USA. [Qin, Jing] NIAID, NIH, Biostat Res Branch, Rockville, MD USA. [Palacios, Gustavo F.] US Army, Med Res Inst Infect Dis, Frederick, MD USA. RP Kuhn, JH (reprint author), NIAID, NIH, Integrated Res Facil Ft Detrick, Frederick, MD USA. EM kuhnjens@mail.nih.gov OI Friedrich, Thomas/0000-0001-9831-6895; Palacios, Gustavo/0000-0001-5062-1938 FU Battelle Memorial Institute; US National Institute of Allergy and Infectious Diseases (NIAID) [HHSN272200700016I]; NIAID Division of Intramural Research; Wisconsin National Primate Research Center Base Grant from the National Center for Research Resources [P51 RR000167]; Office of Research Infrastructure Programs of the National Institutes of Health (NIH) [P51 OD011106]; NIH [R01AI116382]; NIH as part of the joint NIH-NSF Ecology of Infectious Disease program [R01 AI077376]; Office of Research Infrastructure Programs (ORIP) [P51OD011106]; National Research Service Award (NRSA) through Microbes in Health and Disease (MHD) training program at the University of Wisconsin [T32 AI55397]; University of Wisconsin's Medical Scientist Training Program (MSTP) [T32 GM008692] FX This work was funded in part through Battelle Memorial Institute's prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272200700016I. J.C.J. performed this work as an employee of Battelle Memorial Institute. Subcontractors to Battelle Memorial Institute who performed this work are: O.R., R.B., D.R.R., L.H., employees of Charles River Laboratories; V.W-J., J.G.B, Y.C., H.B.S., and J.H.K, employees of Tunnell Government Services, Inc.; M.C., an employee of Lovelace Respiratory Research Institute; and E.Z. and S.M., employees of MRIGlobal Research Institute. This study was also funded, in part, by the NIAID Division of Intramural Research (R.F.J., P.B.J.). The work of M.L., J.T.W., L.H.M., A.M.W., O.C., A.L.B., T.L.G., D.H.O'C., and T.C.F. was supported in part by the Wisconsin National Primate Research Center Base Grant from the National Center for Research Resources (P51 RR000167) and the Office of Research Infrastructure Programs (P51 OD011106) of the National Institutes of Health (NIH); NIH grant R01AI116382; NIH grant TW009237 as part of the joint NIH-NSF Ecology of Infectious Disease program, grant R01 AI077376; and by the Office of Research Infrastructure Programs (ORIP) grant P51OD011106. A.L.B. was additionally supported via a National Research Service Award (NRSA) through the Microbes in Health and Disease (MHD) training program at the University of Wisconsin (T32 AI55397) and University of Wisconsin's Medical Scientist Training Program (MSTP) grant T32 GM008692. NR 30 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2016 VL 7 IS 1 AR e02009-15 DI 10.1128/mBio.02009-15 PG 10 WC Microbiology SC Microbiology GA DJ0ZO UT WOS:000373933100065 PM 26908578 ER PT J AU Lin, J Zhang, MG Tang, YX Wen, B Hu, H Song, JB Liu, YJ Huang, P Chen, XY AF Lin, Jing Zhang, Molly G. Tang, Yuxia Wen, Bronte Hu, Hao Song, Jibing Liu, Yijing Huang, Peng Chen, Xiaoyuan TI Temporal-spatially transformed synthesis and formation mechanism of gold bellflowers SO NANOSCALE LA English DT Article ID PHOTOTHERMAL THERAPY; NANOPARTICLES; NANOSTRUCTURES; THERANOSTICS; SYSTEM AB Anisotropic gold nanostructures with unique plasmonic properties, specifically the strong absorption of light in the near-infrared region (650-900 nm) due to the excitation of plasmon oscillations, have been widely employed as photothermal conversion agents (PTCAs) for cancer photothermal therapy (PTT). However, the reported PTCAs show suboptimal photothermal conversion efficiency (eta), even gold nano-cages (eta = 63%), which limits their biomedical applications. Herein, we fabricated gold bellflowers (GBFs) with an ultrahigh photothermal conversion efficiency (eta = 74%) via a novel liquid/liquid/gas triphasic interface system, using chloroauric acid as a gold source, and o-phenetidine as a reducing agent. The well-defined GBFs with multiple-branched petals show adjustable localized surface plasmon resonance (LSPR) from 760 to 1100 nm by tuning the petal length and circular bottom diameter. Originating from the monophasic and biphasic systems used in the creation of gold nanourchins (GNUs) and gold microspheres (GMPs) respectively, the triphasic interface system successfully produced GBFs. The possible formation mechanisms of GNUs, GMPs, and GBFs in the different systems were also investigated and discussed. We found that the formation mechanism of GNUs and GBFs followed classical crystallization, while the formation of GMPs followed non-classical crystallization. C1 [Lin, Jing; Huang, Peng] Shenzhen Univ, Sch Med, Dept Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China. [Zhang, Molly G.; Tang, Yuxia; Wen, Bronte; Hu, Hao; Song, Jibing; Liu, Yijing; Huang, Peng; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Lin, Jing] NIBIB, LCIMB, NIH, Bethesda, MD 20892 USA. RP Huang, P (reprint author), Shenzhen Univ, Sch Med, Dept Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China.; Huang, P; Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM peng.huang@nih.gov; shawn.chen@nih.gov RI Huang, Peng/R-2480-2016 OI Huang, Peng/0000-0003-3651-7813 FU National Science Foundation of China [81401465, 51573096]; NIBIB, NIH FX This work was supported by the National Science Foundation of China (81401465, 51573096), and the Intramural Research Program (IRP) of the NIBIB, NIH. NR 22 TC 1 Z9 1 U1 6 U2 18 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2016 VL 8 IS 14 BP 7430 EP 7434 DI 10.1039/c5nr04430h PG 5 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA DI8AB UT WOS:000373722000010 PM 26525291 ER PT J AU Munoz, P Aschrafi, A Moya, PR AF Munoz, Pablo Aschrafi, Armaz Moya, Pablo R. TI Connecting Synaptic Activity with Plasticity-Related Gene Expression: From Molecular Mechanisms to Neurological Disorders SO NEURAL PLASTICITY LA English DT Editorial Material ID NF-KAPPA-B; NEURONS C1 [Munoz, Pablo] Univ Valparaiso, Fac Med, Sch Med, Dept Pathol & Physiol, Valparaiso 2341386, Chile. [Munoz, Pablo; Moya, Pablo R.] Univ Valparaiso, Interdisciplinary Ctr Innovat Hlth CIIS, Valparaiso 8380492, Chile. [Aschrafi, Armaz] NIMH, Mol Biol Lab, NIH, Bethesda, MD 20819 USA. [Moya, Pablo R.] Univ Valparaiso, Nucleo Milenio Biol Enfermedades Neurosiquiatr nu, Inst Fisiol, Fac Ciencias, Valparaiso 2360102, Chile. RP Munoz, P (reprint author), Univ Valparaiso, Fac Med, Sch Med, Dept Pathol & Physiol, Valparaiso 2341386, Chile.; Munoz, P (reprint author), Univ Valparaiso, Interdisciplinary Ctr Innovat Hlth CIIS, Valparaiso 8380492, Chile. EM pablo.munozca@uv.cl NR 10 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2016 AR 7149527 DI 10.1155/2016/7149527 PG 3 WC Neurosciences SC Neurosciences & Neurology GA DJ2TW UT WOS:000374059000001 ER PT J AU Zhao, L Zhang, K Bu, WH Xu, XW Jin, H Chang, B Wang, BC Sun, YJ Yang, B Zheng, CY Sun, HC AF Zhao, Liang Zhang, Kai Bu, Wenhuan Xu, Xiaowei Jin, Han Chang, Bei Wang, Banchao Sun, Yingjian Yang, Bai Zheng, Changyu Sun, Hongchen TI Effective delivery of bone morphogenetic protein 2 gene using chitosan-polyethylenimine nanoparticle to promote bone formation SO RSC ADVANCES LA English DT Article ID IN-VIVO; OSTEOGENIC DIFFERENTIATION; STEM-CELLS; BMP-2 GENE; PEI; VECTOR; TRANSFECTION; CYTOTOXICITY; REGENERATION; VITRO AB Treating bone defects is still a challenge in clinical practice. Recently, researchers used human bone morphogenetic protein 2 gene (hBMP-2) to induce osteoblast differentiation and promote new bone formation. However, an efficient way to deliver hBMP-2 still needs to be created. In this study, we evaluated whether chitosan-polyethylenimine (CS-PEI) nanoparticle could effectively deliver hBMP-2 locally with lower or no toxicity and promote osteoblast differentiation and new bone formation in vitro and in vivo. Data demonstrated that the synthesized CS-PEI/hBMP-2 nanoparticle at a W/W ratio of 20 to 1, which was the smallest size (162 nm) and highest zeta potential (24 mV), effectively transfected MC3T3-E1 cells without cytotoxicity in vitro, and had the ability to promote cell proliferation. Interestingly, the CS-PEI/hBMP-2 nanoparticle eliminated disadvantages of lower transfection efficiency from chitosan and cytotoxicity from PEI. RT-QPCR data showed that MC3T3-E1 cells treated with CS-PEI/hBMP-2 nanoparticle dramatically expressed higher levels of BMP-2 and significantly increased gene expressions of Col1 on days 3 and 14, Sp7 on days 3, 7, and 14, and ALP on day 14. Alizarin red staining demonstrated that CS-PEI/hBMP-2 nanoparticle-treated MC3T3-E1 cells significantly increased cell mineralization. These in vitro data suggest that the CS-PEI/hBMP-2 nanoparticle can effectively induce osteogenic differentiation of MC3T3-E1 cells in vitro. Western blot analysis further demonstrated that transgene BMP-2 indeed phosphorylated Smad1/5/8, which indicates that CS-PEI/hBMP-2 nanoparticle affects cell differentiation through a BMP-2 signal pathway. Importantly, in vivo data showed that CSPEI/ hBMP-2 nanoparticle clearly promoted new bone formation at the bone defect area 12 weeks post-implantation. This indicates that synthesized CS-PEI/hBMP-2 nanoparticle has the potential to become a useful therapeutic vector for bone defect treatment with further modification. C1 [Zhao, Liang; Bu, Wenhuan; Xu, Xiaowei; Chang, Bei; Wang, Banchao; Sun, Hongchen] Jilin Univ, Sch Stomatol, Dept Pathol, Changchun 130021, Peoples R China. [Zhang, Kai; Yang, Bai] Jilin Univ, Coll Chem, State Key Lab Supramol Struct & Mat, Changchun 130021, Peoples R China. [Jin, Han] Harbin Med Univ, Affiliated Hosp 2, Sino Russian Inst Hard Tissue Dev & Regenerat, Harbin 150001, Heilongjiang, Peoples R China. [Sun, Yingjian] Jilin Univ, Affiliated Hosp 2, Changchun 130021, Peoples R China. [Zheng, Changyu] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, 10 Room 1A01, Bethesda, MD 20892 USA. RP Sun, HC (reprint author), Jilin Univ, Sch Stomatol, Dept Pathol, Changchun 130021, Peoples R China. EM hcsun@jlu.edu.cn FU National Natural Science Foundation of China [81320108011, 81271111, 30830108]; Graduate Innovation Fund of Jilin University [2015050]; Research Fund for the Doctoral Program of Higher Education of China [233200801830063, 20120061130010]; Science Technology Program of Jilin Province [201201064] FX The authors would like to thank Cindy Clark (NIH Library Editing Service) for reviewing the manuscript. This study was supported by the National Natural Science Foundation of China (81320108011, 81271111, 30830108), the Graduate Innovation Fund of Jilin University (2015050), the Research Fund for the Doctoral Program of Higher Education of China (233200801830063, 20120061130010), and the Science Technology Program of Jilin Province (201201064). NR 43 TC 0 Z9 0 U1 11 U2 19 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2046-2069 J9 RSC ADV JI RSC Adv. PY 2016 VL 6 IS 41 BP 34081 EP 34089 DI 10.1039/c5ra24891d PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA DJ2QI UT WOS:000374049700001 ER PT J AU Brown, TM Fee, E Stepanova, V AF Brown, Theodore M. Fee, Elizabeth Stepanova, Victoria TI The Meaning of "Health for All by the Year 2000'' SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CARE C1 [Brown, Theodore M.] Univ Rochester, Dept Hist, 601 Elmwood Ave, Rochester, NY 14627 USA. [Brown, Theodore M.] Univ Rochester, Dept Publ Hlth Sci, 601 Elmwood Ave, Rochester, NY 14627 USA. [Fee, Elizabeth] Natl Lib Med, Hist Med Div, NIH, Bethesda, MD USA. [Stepanova, Victoria] Univ Rochester, 601 Elmwood Ave, Rochester, NY 14627 USA. RP Brown, TM (reprint author), Univ Rochester, Dept Hist, 601 Elmwood Ave, Rochester, NY 14627 USA. EM Theodore_Brown@urmc.rochester.edu NR 7 TC 1 Z9 1 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2016 VL 106 IS 1 BP 36 EP 39 DI 10.2105/AJPH.2015.302935 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DI3VS UT WOS:000373428000019 PM 26562105 ER PT J AU Klionsky, DJ Abdelmohsen, K Abe, A Abedin, MJ Abeliovich, H Arozena, AA Adachi, H Adams, CM Adams, PD Adeli, K Adhihetty, PJ Adler, SG Agam, G Agarwal, R Aghi, MK Agnello, M Agostinis, P Aguilar, PV Aguirre-Ghiso, J Airoldi, EM Ait-Si-Ali, S Akematsu, T Akporiaye, ET Al-Rubeai, M Albaiceta, GM Albanese, C Albani, D Albert, ML Aldudo, J Algul, H Alirezaei, M Alloza, I Almasan, A Almonte-Beceril, M Alnemri, ES Alonso, C Altan-Bonnet, N Altieri, DC Alvarez, S Alvarez-Erviti, L Alves, S Amadoro, G Amano, A Amantini, C Ambrosio, S Amelio, I Amer, AO Amessou, M Amon, A An, ZY Anania, FA Andersen, SU Andley, UP Andreadi, CK Andrieu-Abadie, N Anel, A Ann, DK Anoopkumar-Dukie, S Antonioli, M Aoki, H Apostolova, N Aquila, S Aquilano, K Araki, K Arama, E Aranda, A Araya, J Arcaro, A Arias, E Arimoto, H Ariosa, AR Armstrong, JL Arnould, T Arsov, I Asanuma, K Askanas, V Asselin, E Atarashi, R Atherton, SS Atkin, JD Attardi, LD Auberger, P Auburger, G Aurelian, L Autelli, R Avagliano, L Avantaggiati, ML Avrahami, L Awale, S Azad, N Bachetti, T Backer, JM Bae, DH Bae, JS Bae, ON Bae, SH Baehrecke, EH Baek, SH Baghdiguian, S Bagniewska-Zadworna, A Bai, H Bai, J Bai, XY Bailly, Y Balaji, KN Balduini, W Ballabio, A Balzan, R Banerjee, R Banhegyi, G Bao, HJ Barbeau, B Barrachina, MD Barreiro, E Bartel, B Bartolome, A Bassham, DC Bassi, MT Bast, RC Basu, A Batista, MT Batoko, H Battino, M Bauckman, K Baumgarner, BL Bayer, KU Beale, R Beaulieu, JF Beck, GR Becker, C Beckham, JD Bedard, PA Bednarski, PJ Begley, TJ Behl, C Behrends, C Behrens, GMN Behrns, KE Bejarano, E Belaid, A Belleudi, F Benard, G Berchem, G Bergamaschi, D Bergami, M Berkhout, B Berliocchi, L Bernard, A Bernard, M Bernassola, F Bertolotti, A Bess, AS Besteiro, S Bettuzzi, S Bhalla, S Bhattacharyya, S Bhutia, SK Biagosch, C Bianchi, MW Biard-Piechaczyk, M Billes, V Bincoletto, C Bingol, B Bird, SW Bitoun, M Bjedov, I Blackstone, C Blanc, L Blanco, GA Blomhoff, HK Boada-Romero, E Bockler, S Boes, M Boesze-Battaglia, K Boise, LH Bolino, A Boman, A Bonaldo, P Bordi, M Bosch, J Botana, LM Botti, J Bou, G Bouche, M Bouchecareilh, M Boucher, MJ Boulton, ME Bouret, SG Boya, P Boyer-Guittaut, M Bozhkov, PV Brady, N Braga, VMM Brancolini, C Braus, GH Bravo-San Pedro, JM Brennan, LA Bresnick, EH Brest, P Bridges, D Bringer, MA Brini, M Brito, GC Brodin, B Brookes, PS Brown, EJ Brown, K Broxmeyer, HE Bruhat, A Brum, PC Brumell, JH Brunetti-Pierri, N Bryson-Richardson, RJ Buch, S Buchan, AM Budak, H Bulavin, DV Bultman, SJ Bultman, SJ Bumbasirevic, V Burelle, Y Burke, RE Burmeister, M Butikofer, P Caberlotto, L Cadwell, K Cahova, M Cai, DS Cai, JJ Cai, Q Calatayud, S Camougrand, N Campanella, M Campbell, GR Campbell, M Campello, S Candau, R Caniggia, I Cantoni, L Cao, LZ Caplan, AB Caraglia, M Cardinali, C Cardoso, SM Carew, JS Carleton, LA Carlin, CR Carloni, S Carlsson, SR Carmona-Gutierrez, D Carneiro, LAM Carnevali, O Carra, S Carrier, A Carroll, B Casas, C Casas, J Cassinelli, G Castets, P Castro-Obregon, S Cavallini, G Ceccherini, I Cecconi, F Cederbaum, AI Cena, V Cenci, S Cerella, C Cervia, D Cetrullo, S Chaachouay, H Chae, HJ Chagin, AS Chai, CY Chakrabarti, G Chamilos, G Chan, EYW Chan, MTV Chandra, D Chandra, P Chang, CP Chang, RCC Chang, TY Chatham, JC Chatterjee, S Chauhan, S Che, YS Cheetham, ME Cheluvappa, R Chen, CJ Chen, G Chen, GC Chen, GQ Chen, HZ Chen, JW Chen, JK Chen, M Chen, MZ Chen, PW Chen, Q Chen, Q Chen, SD Chen, S Chen, SSL Chen, W Chen, WJ Chen, WQ Chen, WL Chen, XM Chen, YH Chen, YG Chen, Y Chen, YY Chen, YS Chen, YJ Chen, YQ Chen, YJ Chen, Z Chen, Z Cheng, A Cheng, CHK Cheng, H Cheong, HS Cherry, S Chesney, J Cheung, CHA Chevet, E Chi, HC Chi, SG Chiacchiera, F Chiang, HL Chiarelli, R Chiariello, M Chieppa, M Chin, LS Chiong, M Chiu, GNC Cho, DH Cho, SG Cho, WC Cho, YY Cho, YS Choi, AMK Choi, EJ Choi, EK Choi, JY Choi, ME Choi, SI Chou, TF Chouaib, S Choubey, D Choubey, V Chow, KC Chowdhury, K Chu, CT Chuang, TH Chun, T Chung, HW Chung, TJ Chung, YL Chwae, YJ Cianfanelli, V Ciarcia, R Ciechomska, IA Ciriolo, MR Cirone, M Claerhout, S Clague, MJ Claria, J Clarke, PGH Clarke, R Clementi, E Cleyrat, C Cnop, M Coccia, EM Cocco, T Codogno, P Coers, J Cohen, EEW Colecchia, D Coletto, L Coll, NS Colucci-Guyon, E Comincini, S Condello, M Cook, KL Coombs, GH Cooper, CD Cooper, JM Coppens, I Corasaniti, MT Corazzari, M Corbalan, R Corcelle-Termeau, E Cordero, MD Corral-Ramos, C Corti, O Cossarizza, A Costelli, P Costes, S Costes, S Coto-Montes, A Cottet, S Couve, E Covey, LR Cowart, LA Cox, JS Coxon, FP Coyne, CB Cragg, MS Craven, RJ Crepaldi, T Crespo, JL Criollo, A Crippa, V Cruz, MT Cuervo, AM Cuezva, JM Cui, TX Cutillas, PR Czaja, MJ Czyzyk-Krzeska, MF Dagda, RK Dahmen, U Dai, CS Dai, WJ Dai, Y Dalby, KN Valle, LD Dalmasso, G D'Amelio, M Damme, M Darfeuille-Michaud, A Dargemont, C Darley-Usmar, VM Dasarathy, S Dasgupta, B Dash, S Dass, CR Davey, HM Davids, LM Davila, D Davis, RJ Dawson, TM Dawson, VL Daza, P de Belleroche, J de Figueiredo, P de Figueiredo, RCBQ de la Fuente, J De Martino, L De Matteis, A De Meyer, GRY De Milito, A De Santi, M de Souza, W De Tata, V De Zio, D Debnath, J Dechant, R Decuypere, JP Deegan, S Dehay, B Del Bello, B Del Re, DP Delage-Mourroux, R Delbridge, LMD Deldicque, L Delorme-Axford, E Deng, YZ Dengjel, J Denizot, M Dent, P Der, CJ Deretic, V Derrien, B Deutsch, E Devarenne, TP Devenish, RJ Di Bartolomeo, S Di Daniele, N Di Domenico, F Di Nardo, A Di Paola, S Di Pietro, A Di Renzo, L DiAntonio, A Diaz-Araya, G Diaz-Laviada, I Diaz-Meco, MT Diaz-Nido, J Dickey, CA Dickson, RC Diederich, M Digard, P Dikic, I Dinesh-Kumar, SP Ding, C Ding, WX Ding, ZF Dini, L Distler, JHW Diwan, A Djavaheri-Mergny, M Dmytruk, K Dobson, RCJ Doetsch, V Dokladny, K Dokudovskaya, S Donadelli, M Dong, XC Dong, XN Dong, Z Donohue, TM Doran, KS D'Orazi, G Dorn, GW Dosenko, V Dridi, S Drucker, L Du, J Du, LL Du, LH du Toit, A Dua, P Duan, L Duann, P Dubey, VK Duchen, MR Duchosal, MA Duez, H Dugail, I Dumit, VI Duncan, MC Dunlop, EA Dunn, WA Dupont, N Dupuis, L Duran, RV Durcan, TM Duvezin-Caubet, S Duvvuri, U Eapen, V Ebrahimi-Fakhari, D Echard, A Eckhart, L Edelstein, CL Edinger, AL Eichinger, L Eisenberg, T Eisenberg-Lerner, A Eissa, NT El-Deiry, WS El-Khoury, V Elazar, Z Eldar-Finkelman, H Elliott, CJH Emanuele, E Emmenegger, U Engedal, N Engelbrecht, AM Engelender, S Enserink, JM Erdmann, R Erenpreisa, J Eri, R Eriksen, JL Erman, A Escalante, R Eskelinen, EL Espert, L Esteban-Martinez, L Evans, TJ Fabri, M Fabrias, G Fabrizi, C Facchiano, A Faergeman, NJ Faggioni, A Fairlie, WD Fan, CH Fan, DP Fan, J Fang, SY Fanto, M Fanzani, A Farkas, T Faure, M Favier, FB Fearnhead, H Federici, M Fei, E Felizardo, TC Feng, H Feng, YB Feng, YC Ferguson, TA Fernandez, AF Fernandez-Barrena, MG Fernandez-Checa, JC Fernandez-Lopez, A Fernandez-Zapico, ME Feron, O Ferraro, E Ferreira-Halder, CV Fesus, L Feuer, R Fiesel, FC Filippi-Chiela, EC Filomeni, G Fimia, GM Fingert, JH Finkbeiner, S Finkel, T Fiorito, F Fisher, PB Flajolet, M Flamigni, F Florey, O Florio, S Floto, RA Folini, M Follo, C Fon, EA Fornai, F Fortunato, F Fraldi, A Franco, R Francois, A Francois, A Frankel, LB Fraser, IDC Frey, N Freyssenet, DG Frezza, C Friedman, SL Frigo, DE Fu, DX Fuentes, JM Fueyo, J Fujitani, Y Fujiwara, Y Fujiya, M Fukuda, M Fulda, S Fusco, C Gabryel, B Gaestel, M Gailly, P Gajewska, M Galadari, S Galili, G Galindo, I Galindo, MF Galliciotti, G Galluzzi, L Galluzzi, L Galy, V Gammoh, N Gandy, S Ganesan, AK Ganesan, S Ganley, IG Gannage, M Gao, FB Gao, F Gao, JX Nannig, LG Vescovi, EG Garcia-Macia, M Garcia-Ruiz, C Garg, AD Garg, PK Gargini, R Gassen, NC Gatica, D Gatti, E Gavard, J Gavathiotis, E Ge, L Ge, PF Ge, SF Gean, PW Gelmetti, V Genazzani, AA 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Yamanaka, K Yamashina, S Yamashiro, S Yan, B Yan, B Yan, X Yan, Z Yanagi, Y Yang, DS Yang, JM Yang, L Yang, MH Yang, PM Yang, P Yang, Q Yang, WN Yang, WY Yang, XS Yang, Y Yang, Y Yang, ZF Yang, ZH Yao, MC Yao, PJ Yao, XF Yao, ZY Yao, ZY Yasui, LS Ye, MX Yedvobnick, B Yeganeh, B Yeh, ES Yeyati, PL Yi, F Yi, L Yin, XM Yip, CK Yoo, YM Yoo, YH Yoon, SY Yoshida, KI Yoshimori, T Young, KH Yu, HM Yu, JJ Yu, JT Yu, J Yu, L Yu, WH Yu, XF Yu, ZP Yuan, JY Yuan, ZM Yue, BYJT Yue, JB Yue, ZY Zacks, DN Zacksenhaus, E Zaffaroni, N Zaglia, T Zakeri, Z Zecchini, V Zeng, JS Zeng, M Zeng, Q Zervos, AS Zhang, DD Zhang, F Zhang, G Zhang, GC Zhang, H Zhang, H Zhang, H Zhang, HB Zhang, J Zhang, J Zhang, JW Zhang, JH Zhang, JP Zhang, L Zhang, L Zhang, L Zhang, L Zhang, MY Zhang, XN Zhang, XD Zhang, Y Zhang, Y Zhang, YJ Zhang, YM Zhang, YJ Zhao, M Zhao, WL Zhao, XN Zhao, YG Zhao, Y Zhao, YC Zhao, YX Zhao, ZD Zhao, ZZJ Zheng, DX Zheng, XL Zheng, XX Zhivotovsky, B Zhong, Q Zhou, GZ Zhou, GF Zhou, HP Zhou, SF 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Chai, Chee-Yin Chakrabarti, Gopal Chamilos, Georgios Chan, Edmond Y. W. Chan, Matthew T. V. Chandra, Dhyan Chandra, Pallavi Chang, Chih-Peng Chang, Raymond Chuen-Chung Chang, Ta Yuan Chatham, John C. Chatterjee, Saurabh Chauhan, Santosh Che, Yongsheng Cheetham, Michael E. Cheluvappa, Rajkumar Chen, Chun-Jung Chen, Gang Chen, Guang-Chao Chen, Guoqiang Chen, Hongzhuan Chen, Jeff W. Chen, Jian-Kang Chen, Min Chen, Mingzhou Chen, Peiwen Chen, Qi Chen, Quan Chen, Shang-Der Chen, Si Chen, Steve S-L Chen, Wei Chen, Wei-Jung Chen, Wen Qiang Chen, Wenli Chen, Xiangmei Chen, Yau-Hung Chen, Ye-Guang Chen, Yin Chen, Yingyu Chen, Yongshun Chen, Yu-Jen Chen, Yue-Qin Chen, Yujie Chen, Zhen Chen, Zhong Cheng, Alan Cheng, Christopher H. K. Cheng, Hua Cheong, Heesun Cherry, Sara Chesney, Jason Cheung, Chun Hei Antonio Chevet, Eric Chi, Hsiang Cheng Chi, Sung-Gil Chiacchiera, Fulvio Chiang, Hui-Ling Chiarelli, Roberto Chiariello, Mario Chieppa, Marcello Chin, Lih-Shen Chiong, Mario Chiu, Gigi N. C. 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Ding, Chan Ding, Wen-Xing Ding, Zufeng Dini, Luciana Distler, Joerg H. W. Diwan, Abhinav Djavaheri-Mergny, Mojgan Dmytruk, Kostyantyn Dobson, Renwick C. J. Doetsch, Volker Dokladny, Karol Dokudovskaya, Svetlana Donadelli, Massimo Dong, X. Charlie Dong, Xiaonan Dong, Zheng Donohue, Terrence M., Jr. Doran, Kelly S. D'Orazi, Gabriella Dorn, Gerald W., II Dosenko, Victor Dridi, Sami Drucker, Liat Du, Jie Du, Li-Lin Du, Lihuan du Toit, Andre Dua, Priyamvada Duan, Lei Duann, Pu Dubey, Vikash Kumar Duchen, Michael R. Duchosal, Michel A. Duez, Helene Dugail, Isabelle Dumit, Veronica I. Duncan, Mara C. Dunlop, Elaine A. Dunn, William A., Jr. Dupont, Nicolas Dupuis, Luc Duran, Raul V. Durcan, Thomas M. Duvezin-Caubet, Stephane Duvvuri, Umamaheswar Eapen, Vinay Ebrahimi-Fakhari, Darius Echard, Arnaud Eckhart, Leopold Edelstein, Charles L. Edinger, Aimee L. Eichinger, Ludwig Eisenberg, Tobias Eisenberg-Lerner, Avital Eissa, N. Tony El-Deiry, Wafik S. El-Khoury, Victoria Elazar, Zvulun Eldar-Finkelman, Hagit Elliott, Chris J. H. Emanuele, Enzo Emmenegger, Urban Engedal, Nikolai Engelbrecht, Anna-Mart Engelender, Simone Enserink, Jorrit M. Erdmann, Ralf Erenpreisa, Jekaterina Eri, Rajaraman Eriksen, Jason L. Erman, Andreja Escalante, Ricardo Eskelinen, Eeva-Liisa Espert, Lucile Esteban-Martinez, Lorena Evans, Thomas J. Fabri, Mario Fabrias, Gemma Fabrizi, Cinzia Facchiano, Antonio Faergeman, Nils J. Faggioni, Alberto Fairlie, W. Douglas Fan, Chunhai Fan, Daping Fan, Jie Fang, Shengyun Fanto, Manolis Fanzani, Alessandro Farkas, Thomas Faure, Mathias Favier, Francois B. Fearnhead, Howard Federici, Massimo Fei, Erkang Felizardo, Tania C. Feng, Hua Feng, Yibin Feng, Yuchen Ferguson, Thomas A. Fernandez, Alvaro F. Fernandez-Barrena, Maite G. Fernandez-Checa, Jose C. Fernandez-Lopez, Arsenio Fernandez-Zapico, Martin E. Feron, Olivier Ferraro, Elisabetta Ferreira-Halder, Carmen Verissima Fesus, Laszlo Feuer, Ralph Fiesel, Fabienne C. Filippi-Chiela, Eduardo C. Filomeni, Giuseppe Fimia, Gian Maria Fingert, John H. Finkbeiner, Steven Finkel, Toren Fiorito, Filomena Fisher, Paul B. Flajolet, Marc Flamigni, Flavio Florey, Oliver Florio, Salvatore Floto, R. Andres Folini, Marco Follo, Carlo Fon, Edward A. Fornai, Francesco Fortunato, Franco Fraldi, Alessandro Franco, Rodrigo Francois, Arnaud Francois, Aurelie Frankel, Lisa B. Fraser, Iain D. C. Frey, Norbert Freyssenet, Damien G. Frezza, Christian Friedman, Scott L. Frigo, Daniel E. Fu, Dongxu Fuentes, Jose M. Fueyo, Juan Fujitani, Yoshio Fujiwara, Yuuki Fujiya, Mikihiro Fukuda, Mitsunori Fulda, Simone Fusco, Carmela Gabryel, Bozena Gaestel, Matthias Gailly, Philippe Gajewska, Malgorzata Galadari, Sehamuddin Galili, Gad Galindo, Inmaculada Galindo, Maria F. Galliciotti, Giovanna Galluzzi, Lorenzo Galluzzi, Luca Galy, Vincent Gammoh, Noor Gandy, Sam Ganesan, Anand K. Ganesan, Swamynathan Ganley, Ian G. Gannage, Monique Gao, Fen-Biao Gao, Feng Gao, Jian-Xin Garcia Nannig, Lorena Vescovi, Eleonora Garcia Garcia-Macia, Marina Garcia-Ruiz, Carmen Garg, Abhishek D. Garg, Pramod Kumar Gargini, Ricardo Gassen, Nils Christian Gatica, Damian Gatti, Evelina Gavard, Julie Gavathiotis, Evripidis Ge, Liang Ge, Pengfei Ge, Shengfang Gean, Po-Wu Gelmetti, Vania Genazzani, Armando A. Geng, Jiefei Genschik, Pascal Gerner, Lisa Gestwicki, Jason E. Gewirtz, David A. Ghavami, Saeid Ghigo, Eric Ghosh, Debabrata Giammarioli, Anna Maria Giampieri, Francesca Giampietri, Claudia Giatromanolaki, Alexandra Gibbings, Derrick J. Gibellini, Lara Gibson, Spencer B. Ginet, Vanessa Giordano, Antonio Giorgini, Flaviano Giovannetti, Elisa Girardin, Stephen E. Gispert, Suzana Giuliano, Sandy Gladson, Candece L. Glavic, Alvaro Gleave, Martin Godefroy, Nelly Gogal, Robert M., Jr. Gokulan, Kuppan Goldman, Gustavo H. Goletti, Delia Goligorsky, Michael S. Gomes, Aldrin V. Gomes, Ligia C. 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Iyer, Anand Krishnan V. Izquierdo, Jose M. Izumi, Yotaro Izzo, Valentina Jaeaettelae, Marja Jaber, Nadia Jackson, Daniel John Jackson, William T. Jacob, Tony George Jacques, Thomas S. Jagannath, Chinnaswamy Jain, Ashish Jana, Nihar Ranjan Jang, Byoung Kuk Jani, Alkesh Janji, Bassam Jannig, Paulo Roberto Jansson, Patric J. Jean, Steve Jendrach, Marina Jeon, Ju-Hong Jessen, Niels Jeung, Eui-Bae Jia, Kailiang Jia, Lijun Jiang, Hong Jiang, Hongchi Jiang, Liwen Jiang, Teng Jiang, Xiaoyan Jiang, Xuejun Jiang, Xuejun Jiang, Ying Jiang, Yongjun Jimenez, Alberto Jin, Cheng Jin, Hongchuan Jin, Lei Jin, Meiyan Jin, Shengkan Jinwal, Umesh Kumar Jo, Eun-Kyeong Johansen, Terje Johnson, Daniel E. Johnson, Gail V. W. Johnson, James D. Jonasch, Eric Jones, Chris Joosten, Leo A. B. Jordan, Joaquin Joseph, Anna-Maria Joseph, Bertrand Joubert, Annie M. Ju, Dianwen Ju, Jingfang Juan, Hsueh-Fen Juenemann, Katrin Juhasz, Gabor Jung, Hye Seung Jung, Jae U. Jung, Yong-Keun Jungbluth, Heinz Justice, Matthew J. Jutten, Barry Kaakoush, Nadeem O. Kaarniranta, Kai Kaasik, Allen Kabuta, Tomohiro Kaeffer, Bertrand Kagedal, Katarina Kahana, Alon Kajimura, Shingo Kakhlon, Or Kalia, Manjula Kalvakolanu, Dhan V. Kamada, Yoshiaki Kambas, Konstantinos Kaminskyy, Vitaliy O. Kampinga, Harm H. Kandouz, Mustapha Kang, Chanhee Kang, Rui Kang, Tae-Cheon Kanki, Tomotake Kanneganti, Thirumala-Devi Kanno, Haruo Kanthasamy, Anumantha G. Kantorow, Marc Kaparakis-Liaskos, Maria Kapuy, Orsolya Karantza, Vassiliki Karim, Md Razaul Karmakar, Parimal Kaser, Arthur Kaushik, Susmita Kawula, Thomas Kaynar, A. Murat Ke, Po-Yuan Ke, Zun-Ji Kehrl, John H. Keller, Kate E. Kemper, Jongsook Kim Kenworthy, Anne K. Kepp, Oliver Kern, Andreas Kesari, Santosh Kessel, David Ketteler, Robin Kettelhut, Isis do Carmo Khambu, Bilon Khan, Muzamil Majid Khandelwal, Vinoth K. M. Khare, Sangeeta Kiang, Juliann G. Kiger, Amy A. Kihara, Akio Kim, Arianna L. Kim, Cheol Hyeon Kim, Deok Ryong Kim, Do-Hyung Kim, Eung Kweon Kim, Hye Young Kim, Hyung-Ryong Kim, Jae-Sung Kim, Jeong Hun Kim, Jin Cheon Kim, Jin Hyoung Kim, Kwang Woon Kim, Michael D. Kim, Moon-Moo Kim, Peter K. Kim, Seong Who Kim, Soo-Youl Kim, Yong-Sun Kim, Yonghyun Kimchi, Adi Kimmelman, Alec C. Kimura, Tomonori King, Jason S. Kirkegaard, Karla Kirkin, Vladimir Kirshenbaum, Lorrie A. Kishi, Shuji Kitajima, Yasuo Kitamoto, Katsuhiko Kitaoka, Yasushi Kitazato, Kaio Kley, Rudolf A. Klimecki, Walter T. Klinkenberg, Michael Klucken, Jochen Knaevelsrud, Helene Knecht, Erwin Knuppertz, Laura Ko, Jiunn-Liang Kobayashi, Satoru Koch, Jan C. Koechlin-Ramonatxo, Christelle Koenig, Ulrich Ko, Young Ho Koehler, Katja Kohlwein, Sepp D. Koike, Masato Komatsu, Masaaki Kominami, Eiki Kong, Dexin Kong, Hee Jeong Konstantakou, Eumorphia G. Kopp, Benjamin T. Korcsmaros, Tamas Korhonen, Laura Korolchuk, Viktor I. Koshkina, Nadya V. Kou, Yanjun Koukourakis, Michael I. Koumenis, Constantinos Kovacs, Attila L. Kovacs, Tibor Kovacs, Werner J. Koya, Daisuke Kraft, Claudine Krainc, Dimitri Kramer, Helmut Kravic-Stevovic, Tamara Krek, Wilhelm Kretz-Remy, Carole Krick, Roswitha Krishnamurthy, Malathi Kriston-Vizi, Janos Kroemer, Guido Kruer, Michael C. Kruger, Rejko Ktistakis, Nicholas T. Kuchitsu, Kazuyuki Kuhn, Christian Kumar, Addanki Pratap Kumar, Anuj Kumar, Ashok Kumar, Deepak Kumar, Dhiraj Kumar, Rakesh Kumar, Sharad Kundu, Mondira Kung, Hsing-Jien Kuno, Atsushi Kuo, Sheng-Han Kuret, Jeff Kurz, Tino Kwok, Terry Kwon, Taeg Kyu Kwon, Yong Tae Kyrmizi, Irene La Spada, Albert R. Lafont, Frank Lahm, Tim Lakkaraju, Aparna Lam, Truong Lamark, Trond Lancel, Steve Landowski, Terry H. Lane, Darius J. R. Lane, Jon D. Lanzi, Cinzia Lapaquette, Pierre Lapierre, Louis R. Laporte, Jocelyn Laukkarinen, Johanna Laurie, Gordon W. Lavandero, Sergio Lavie, Lena LaVoie, Matthew J. Law, Betty Yuen Kwan Law, Helen Ka-wai Law, Kelsey B. Layfield, Robert Lazo, Pedro A. Le Cam, Laurent Le Roch, Karine G. Le Stunff, Herve Leardkamolkarn, Vijittra Lecuit, Marc Lee, Byung-Hoon Lee, Che-Hsin Lee, Erinna F. Lee, Gyun Min Lee, He-Jin Lee, Hsinyu Lee, Jae Keun Lee, Jongdae Lee, Ju-Hyun Lee, Jun Hee Lee, Michael Lee, Myung-Shik Lee, Patty J. Lee, Sam W. Lee, Seung-Jae Lee, Shiow-Ju Lee, Stella Y. Lee, Sug Hyung Lee, Sung Sik Lee, Sung-Joon Lee, Sunhee Lee, Ying-Ray Lee, Yong J. Lee, Young H. Leeuwenburgh, Christiaan Lefort, Sylvain Legouis, Renaud Lei, Jinzhi Lei, Qun-Ying Leib, David A. Leibowitz, Gil Lekli, Istvan Lemaire, Stephane D. Lemasters, John J. Lemberg, Marius K. Lemoine, Antoinette Leng, Shuilong Lenz, Guido Lenzi, Paola Lerman, Lilach O. Barbato, Daniele Lettieri Leu, Julia I-Ju Leung, Hing Y. Levine, Beth Lewis, Patrick A. Lezoualc'h, Frank Li, Chi Li, Faqiang Li, Feng-Jun Li, Jun Li, Ke Li, Lian Li, Min Li, Min Li, Qiang Li, Rui Li, Sheng Li, Wei Li, Wei Li, Xiaotao Li, Yumin Lian, Jiqin Liang, Chengyu Liang, Qiangrong Liao, Yulin Liberal, Joana Liberski, Pawel P. Lie, Pearl Lieberman, Andrew P. Lim, Hyunjung Jade Lim, Kah-Leong Lim, Kyu Lima, Raquel T. Lin, Chang-Shen Lin, Chiou-Feng Lin, Fang Lin, Fangming Lin, Fu-Cheng Lin, Kui Lin, Kwang-Huei Lin, Pei-Hui Lin, Tianwei Lin, Wan-Wan Lin, Yee-Shin Lin, Yong Linden, Rafael Lindholm, Dan Lindqvist, Lisa M. Lingor, Paul Linkermann, Andreas Liotta, Lance A. Lipinski, Marta M. Lira, Vitor A. Lisanti, Michael P. Liton, Paloma B. Liu, Bo Liu, Chong Liu, Chun-Feng Liu, Fei Liu, Hung-Jen Liu, Jianxun Liu, Jing-Jing Liu, Jing-Lan Liu, Ke Liu, Leyuan Liu, Liang Liu, Quentin Liu, Rong-Yu Liu, Shiming Liu, Shuwen Liu, Wei Liu, Xian-De Liu, Xiangguo Liu, Xiao-Hong Liu, Xinfeng Liu, Xu Liu, Xueqin Liu, Yang Liu, Yule Liu, Zexian Liu, Zhe Liuzzi, Juan P. Lizard, Gerard Ljujic, Mila Lodhi, Irfan J. Logue, Susan E. Lokeshwar, Bal L. Long, Yun Chau Lonial, Sagar Loos, Benjamin Lopez-Otin, Carlos Lopez-Vicario, Cristina Lorente, Mar Lorenzi, Philip L. Lorincz, Peter Los, Marek Lotze, Michael T. Lovat, Penny E. Lu, Binfeng Lu, Bo Lu, Jiahong Lu, Qing Lu, She-Min Lu, Shuyan Lu, Yingying Luciano, Federic Luckhart, Shirley Lucocq, John Milton Ludovico, Paula Lugea, Aurelia Lukacs, Nicholas W. Lum, Julian J. Lund, Anders H. Luo, Honglin Luo, Jia Luo, Shouqing Luparello, Claudio Lyons, Timothy Ma, Jianjie Ma, Yi Ma, Yong Ma, Zhenyi Machado, Juliano Machado-Santelli, Glaucia M. Macian, Fernando MacIntosh, Gustavo C. MacKeigan, Jeffrey P. Macleod, Kay F. MacMicking, John D. MacMillan-Crow, Lee Ann Madeo, Frank Madesh, Muniswamy Madrigal-Matute, Julio Maeda, Akiko Maeda, Tatsuya Maegawa, Gustavo Maellaro, Emilia Maes, Hannelore Magarinos, Marta Maiese, Kenneth Maiti, Tapas K. Maiuri, Luigi Maiuri, Maria Chiara Maki, Carl G. Malli, Roland Malorni, Walter Maloyan, Alina Mami-Chouaib, Fathia Man, Na Mancias, Joseph D. Mandelkow, Eva-Maria Mandell, Michael A. Manfredi, Angelo A. Manie, Serge N. Manzoni, Claudia Mao, Kai Mao, Zixu Mao, Zong-Wan Marambaud, Philippe Marconi, Anna Maria Marelja, Zvonimir Marfe, Gabriella Margeta, Marta Margittai, Eva Mari, Muriel Mariani, Francesca V. Marin, Concepcio Marinelli, Sara Marino, Guillermo Markovic, Ivanka Marquez, Rebecca Martelli, Alberto M. Martens, Sascha Martin, Katie R. Martin, Seamus J. Martin, Shaun Martin-Acebes, Miguel A. Martin-Sanz, Paloma Martinand-Mari, Camille Martinet, Wim Martinez, Jennifer Martinez-Lopez, Nuria Martinez-Outschoorn, Ubaldo Martinez-Velazquez, Moises Martinez-Vicente, Marta Martins, Waleska Kerllen Mashima, Hirosato Mastrianni, James A. Matarese, Giuseppe Matarrese, Paola Mateo, Roberto Matoba, Satoaki Matsumoto, Naomichi Matsushita, Takehiko Matsuura, Akira Matsuzawa, Takeshi Mattson, Mark P. Matus, Soledad Maugeri, Norma Mauvezin, Caroline Mayer, Andreas Maysinger, Dusica Mazzolini, Guillermo D. McBrayer, Mary Kate McCall, Kimberly McCormick, Craig McInerney, Gerald M. McIver, Skye C. McKenna, Sharon McMahon, John J. McNeish, Iain A. Mechta-Grigoriou, Fatima Medema, Jan Paul Medina, Diego L. Megyeri, Klara Mehrpour, Maryam Mehta, Jawahar L. Mei, Yide Meier, Ute-Christiane Meijer, Alfred J. Melendez, Alicia Melino, Gerry Melino, Sonia Tenorio de Melo, Edesio Jose Mena, Maria A. Meneghini, Marc D. Menendez, Javier A. Menezes, Regina Meng, Liesu Meng, Ling-hua Meng, Songshu Menghini, Rossella Menko, A. Sue Menna-Barreto, Rubem F. S. Menon, Manoj B. Meraz-Rios, Marco A. Merla, Giuseppe Merlini, Luciano Merlot, Angelica M. Meryk, Andreas Meschini, Stefania Meyer, Joel N. Mi, Man-Tian Miao, Chao-Yu Micale, Lucia Michaeli, Simon Michiels, Carine Migliaccio, Anna Rita Mihailidou, Anastasia Susie Mijaljica, Dalibor Mikoshiba, Katsuhiko Milan, Enrico Miller-Fleming, Leonor Mills, Gordon B. Mills, Ian G. Minakaki, Georgia Minassian, Berge A. Ming, Xiu-Fen Minibayeva, Farida Minina, Elena A. Mintern, Justine D. Minucci, Saverio Miranda-Vizuete, Antonio Mitchell, Claire H. Miyamoto, Shigeki Miyazawa, Keisuke Mizushima, Noboru Mnich, Katarzyna Mograbi, Baharia Mohseni, Simin Moita, Luis Ferreira Molinari, Marco Molinari, Maurizio Moller, Andreas Buch Mollereau, Bertrand Mollinedo, Faustino Monick, Martha M. Monick, Martha M. Montagnaro, Serena Montell, Craig Moore, Darren J. Moore, Michael N. Mora-Rodriguez, Rodrigo Moreira, Paula I. Morel, Etienne Morelli, Maria Beatrice Moreno, Sandra Morgan, Michael J. Moris, Arnaud Moriyasu, Yuji Morrison, Janna L. Morrison, Lynda A. Morselli, Eugenia Moscat, Jorge Moseley, Pope L. Mostowy, Serge Motori, Elisa Mottet, Denis Mottram, Jeremy C. Moussa, Charbel E-H Mpakou, Vassiliki E. Mukhtar, Hasan Levy, Jean M. Mulcahy Muller, Sylviane Munoz-Moreno, Raquel Munoz-Pinedo, Cristina Muenz, Christian Murphy, Maureen E. Murray, James T. Murthy, Aditya Mysorekar, Indira U. Nabi, Ivan R. Nabissi, Massimo Nader, Gustavo A. Nagahara, Yukitoshi Nagai, Yoshitaka Nagata, Kazuhiro Nagelkerke, Anika Nagy, Peter Naidu, Samisubbu R. Nair, Sreejayan Nakano, Hiroyasu Nakatogawa, Hitoshi Nanjundan, Meera Napolitano, Gennaro Naqvi, Naweed I. Nardacci, Roberta Narendra, Derek P. Narita, Masashi Nascimbeni, Anna Chiara Natarajan, Ramesh Navegantes, Luiz C. Nawrocki, Steffan T. Nazarko, Taras Y. Nazarko, Volodymyr Y. Neill, Thomas Neri, Luca M. Netea, Mihai G. Netea-Maier, Romana T. Neves, Bruno M. Ney, Paul A. Nezis, Ioannis P. Nguyen, Hang T. T. Huu Phuc Nguyen Nicot, Anne-Sophie Nilsen, Hilde Nilsson, Per Nishimura, Mikio Nishino, Ichizo Niso-Santano, Mireia Niu, Hua Nixon, Ralph A. Njar, Vincent C. O. Noda, Takeshi Noegel, Angelika A. Nolte, Elsie Magdalena Norberg, Erik Norga, Koenraad K. Noureini, Sakineh Kazemi Notomi, Shoji Notterpek, Lucia Nowikovsky, Karin Nukina, Nobuyuki Nuernberger, Thorsten O'Donnell, Valerie B. O'Donovan, Tracey O'Dwyer, Peter J. Oehme, Ina Oeste, Clara L. Ogawa, Michinaga Ogretmen, Besim Ogura, Yuji Oh, Young J. Ohmuraya, Masaki Ohshima, Takayuki Ojha, Rani Okamoto, Koji Okazaki, Toshiro Oliver, F. Javier Ollinger, Karin Olsson, Stefan Orban, Daniel P. Ordonez, Paulina Orhon, Idil Orosz, Laszlo O'Rourke, Eyleen J. Orozco, Helena Ortega, Angel L. Ortona, Elena Osellame, Laura D. Oshima, Junko Oshima, Shigeru Osiewacz, Heinz D. Otomo, Takanobu Otsu, Kinya Ou, Jing-hsiung James Outeiro, Tiago F. Ouyang, Dong-yun Ouyang, Hongjiao Overholtzer, Michael Ozbun, Michelle A. Ozdinler, P. Hande Ozpolat, Bulent Pacelli, Consiglia Paganetti, Paolo Page, Guylene Pages, Gilles Pagnini, Ugo Pajak, Beata Pak, Stephen C. Pakos-Zebrucka, Karolina Pakpour, Nazzy Palkova, Zdena Palladino, Francesca Pallauf, Kathrin Pallet, Nicolas Palmieri, Marta Paludan, Soren R. Palumbo, Camilla Palumbo, Silvia Pampliega, Olatz Pan, Hongming Pan, Wei Panaretakis, Theocharis Pandey, Aseem Pantazopoulou, Areti Papackova, Zuzana Papademetrio, Daniela L. Papassideri, Issidora Papini, Alessio Parajuli, Nirmala Pardo, Julian Parekh, Vrajesh V. Parenti, Giancarlo Park, Jong-In Park, Junsoo Park, Ohkmae K. Parker, Roy Parlato, Rosanna Parys, Jan B. Parzych, Katherine R. Pasquet, Jean-Max Pasquier, Benoit Pasumarthi, Kishore B. S. Patschan, Daniel Patterson, Cam Pattingre, Sophie Pattison, Scott Pause, Arnim Pavenstaedt, Hermann Pavone, Flaminia Pedrozo, Zully Pena, Fernando J. Penalva, Miguel A. Pende, Mario Peng, Jianxin Penna, Fabio Penninger, Josef M. Pensalfini, Anna Pepe, Salvatore Pereira, Gustavo J. S. Pereira, Paulo C. Perez-de la Cruz, Veronica Esther Perez-Perez, Maria Perez-Rodriguez, Diego Perez-Sala, Dolores Perier, Celine Perl, Andras Perlmutter, David H. Perrotta, Ida Pervaiz, Shazib Pesonen, Maija Pessin, Jeffrey E. Peters, Godefridus J. Petersen, Morten Petrache, Irina Petrof, Basil J. Petrovski, Goran Phang, James M. Piacentini, Mauro Pierdominici, Marina Pierre, Philippe Pierrefite-Carle, Valerie Pietrocola, Federico Pimentel-Muinos, Felipe X. Pinar, Mario Pineda, Benjamin Pinkas-Kramarski, Ronit Pinti, Marcello Pinton, Paolo Piperdi, Bilal Piret, James M. Platanias, Leonidas C. Platta, Harald W. Plowey, Edward D. Poggeler, Stefanie Poirot, Marc Polcic, Peter Poletti, Angelo Poon, Audrey H. Popelka, Hana Popova, Blagovesta Poprawa, Izabela Poulose, Shibu M. Poulton, Joanna Powers, Scott K. Powers, Ted Pozuelo-Rubio, Mercedes Prak, Krisna Prange, Reinhild Prescott, Mark Priault, Muriel Prince, Sharon Proia, Richard L. Proikas-Cezanne, Tassula Prokisch, Holger Promponas, Vasilis J. Przyklenk, Karin Puertollano, Rosa Pugazhenthi, Subbiah Puglielli, Luigi Pujol, Aurora Puyal, Julien Pyeon, Dohun Qi, Xin Qian, Wen-bin Qin, Zheng-Hong Qiu, Yu Qu, Ziwei Quadrilatero, Joe Quinn, Frederick Raben, Nina Rabinowich, Hannah Radogna, Flavia Ragusa, Michael J. Rahmani, Mohamed Raina, Komal Ramanadham, Sasanka Ramesh, Rajagopal Rami, Abdelhaq Randall-Demllo, Sarron Randow, Felix Rao, Hai Rao, V. Ashutosh Rasmussen, Blake B. Rasse, Tobias M. Ratovitski, Edward A. Rautou, Pierre-Emmanuel Ray, Swapan K. Razani, Babak Reed, Bruce H. Reggiori, Fulvio Rehm, Markus Reichert, Andreas S. Rein, Theo Reiner, David J. Reits, Eric Ren, Jun Ren, Xingcong Renna, Maurizio Reusch, Jane E. B. Revuelta, Jose L. Reyes, Leticia Rezaie, Alireza R. Richards, Robert I. Richardson, Des R. Richetta, Clemence Riehle, Michael A. Rihn, Bertrand H. Rikihisa, Yasuko Riley, Brigit E. Rimbach, Gerald Rippo, Maria Rita Ritis, Konstantinos Rizzi, Federica Rizzo, Elizete Roach, Peter J. Robbins, Jeffrey Roberge, Michel Roca, Gabriela Roccheri, Maria Carmela Rocha, Sonia Rodrigues, Cecilia M. P. Rodriguez, Clara I. Rodriguez de Cordoba, Santiago Rodriguez-Muela, Natalia Roelofs, Jeroen Rogov, Vladimir V. Rohn, Troy T. Rohrer, Baerbel Romanelli, Davide Romani, Luigina Silvia Romano, Patricia Roncero, M. Isabel G. Luis Rosa, Jose Rosello, Alicia Rosen, Kirill V. Rosenstiel, Philip Rost-Roszkowska, Magdalena Roth, Kevin A. Roue, Gael Rouis, Mustapha Rouschop, Kasper M. Ruan, Daniel T. Ruano, Diego Rubinsztein, David C. Rucker, Edmund B., III Rudich, Assaf Rudolf, Emil Rudolf, Ruediger Ruegg, Markus A. Ruiz-Roldan, Carmen Ruparelia, Avnika Ashok Rusmini, Paola Russ, David W. Russo, Gian Luigi Russo, Giuseppe Russo, Rossella Rusten, Tor Erik Ryabovol, Victoria Ryan, Kevin M. Ryter, Stefan W. Sabatini, David M. Sacher, Michael Sachse, Carsten Sack, Michael N. Sadoshima, Junichi Saftig, Paul Sagi-Eisenberg, Ronit Sahni, Sumit Saikumar, Pothana Saito, Tsunenori Saitoh, Tatsuya Sakakura, Koichi Sakoh-Nakatogawa, Machiko Sakuraba, Yasuhito Salazar-Roa, Maria Salomoni, Paolo Saluja, Ashok K. Salvaterra, Paul M. Salvioli, Rosa Samali, Afshin Sanchez, Anthony M. J. Sanchez-Alcazar, Jose A. Sanchez-Prieto, Ricardo Sandri, Marco Sanjuan, Miguel A. Santaguida, Stefano Santambrogio, Laura Santoni, Giorgio dos Santos, Claudia Nunes Saran, Shweta Sardiello, Marco Sargent, Graeme Sarkar, Pallabi Sarkar, Sovan Sarrias, Maria Rosa Sarwal, Minnie M. Sasakawa, Chihiro Sasaki, Motoko Sass, Miklos Sato, Ken Sato, Miyuki Satriano, Joseph Savaraj, Niramol Saveljeva, Svetlana Schaefer, Liliana Schaible, Ulrich E. Scharl, Michael Schatzl, Hermann M. Schekman, Randy Scheper, Wiep Schiavi, Alfonso Schipper, Hyman M. Schmeisser, Hana Schmidt, Jens Schmitz, Ingo Schneider, Bianca E. Schneider, E. Marion Schneider, Jaime L. Schon, Eric A. Schoenenberger, Miriam J. Schoenthal, Axel H. Schorderet, Daniel F. Schroeder, Bernd Schuck, Sebastian Schulze, Ryan J. Schwarten, Melanie Schwarz, Thomas L. Sciarretta, Sebastiano Scotto, Kathleen Scovassi, A. Ivana Screaton, Robert A. Screen, Mark Seca, Hugo Sedej, Simon Segatori, Laura Segev, Nava Seglen, Per O. Segui-Simarro, Jose M. Segura-Aguilar, Juan Seiliez, Iban Seki, Ekihiro Sell, Christian Semenkovich, Clay F. Semenza, Gregg L. Sen, Utpal Serra, Andreas L. Serrano-Puebla, Ana Sesaki, Hiromi Setoguchi, Takao Settembre, Carmine Shacka, John J. Shajahan-Haq, Ayesha N. Shapiro, Irving M. Sharma, Shweta She, Hua Shen, C-K James Shen, Chiung-Chyi Shen, Han-Ming Shen, Sanbing Shen, Weili Sheng, Rui Sheng, Xianyong Sheng, Zu-Hang Shepherd, Trevor G. Shi, Junyan Shi, Qiang Shi, Qinghua Shi, Yuguang Shibutani, Shusaku Shibuya, Kenichi Shidoji, Yoshihiro Shieh, Jeng-Jer Shih, Chwen-Ming Shimada, Yohta Shimizu, Shigeomi Shin, Dong Wook Shinohara, Mari L. Shintani, Michiko Shintani, Takahiro Shioi, Tetsuo Shirabe, Ken Shiri-Sverdlov, Ronit Shirihai, Orian Shore, Gordon C. Shu, Chih-Wen Shukla, Deepak Sibirny, Andriy A. Sica, Valentina Sigurdson, Christina J. Sigurdsson, Einar M. Sijwali, Puran Singh Sikorska, Beata Silveira, Wilian A. Silvente-Poirot, Sandrine Silverman, Gary A. Simak, Jan Simmet, Thomas Simon, Anna Katharina Simon, Hans-Uwe Simone, Cristiano Simons, Matias Simonsen, Anne Singh, Rajat Singh, Shivendra V. Singh, Shrawan K. Sinha, Debasish Sinha, Sangita Sinicrope, Frank A. Sirko, Agnieszka Sirohi, Kapil Sishi, Balindiwe J. N. Sittler, Annie Siu, Parco M. Sivridis, Efthimios Skwarska, Anna Slack, Ruth Slaninova, Iva Slavov, Nikolai Smaili, Soraya S. Smalley, Keiran S. M. Smith, Duncan R. Soenen, Stefaan J. Soleimanpour, Scott A. Solhaug, Anita Somasundaram, Kumaravel Son, Jin H. Sonawane, Avinash Song, Chunjuan Song, Fuyong Song, Hyun Kyu Song, Ju-Xian Song, Wei Soo, Kai Y. Sood, Anil K. Soong, Tuck Wah Soontornniyomkij, Virawudh Sorice, Maurizio Sotgia, Federica Soto-Pantoja, David R. Sotthibundhu, Areechun Sousa, Maria Joao Spaink, Herman P. Span, Paul N. Spang, Anne Sparks, Janet D. Speck, Peter G. Spector, Stephen A. Spies, Claudia D. Springer, Wolfdieter St Clair, Daret Stacchiotti, Alessandra Staels, Bart Stang, Michael T. Starczynowski, Daniel T. Starokadomskyy, Petro Steegborn, Clemens Steele, John W. Stefanis, Leonidas Steffan, Joan Stellrecht, Christine M. Stenmark, Harald Stepkowski, Tomasz M. Stern, Stephan T. Stevens, Craig Stockwell, Brent R. Stoka, Veronika Storchova, Zuzana Stork, Bjoern Stratoulias, Vassilis Stravopodis, Dimitrios J. Strnad, Pavel Strohecker, Anne Marie Stroem, Anna-Lena Stromhaug, Per Stulik, Jiri Su, Yu-Xiong Su, Zhaoliang Subauste, Carlos S. Subramaniam, Srinivasa Sue, Carolyn M. Suh, Sang Won Sui, Xinbing Sukseree, Supawadee Sulzer, David Sun, Fang-Lin Sun, Jiaren Sun, Jun Sun, Shi-Yong Sun, Yang Sun, Yi Sun, Yingjie Sundaramoorthy, Vinod Sung, Joseph Suzuki, Hidekazu Suzuki, Kuninori Suzuki, Naoki Suzuki, Tadashi Suzuki, Yuichiro J. Swanson, Michele S. Swanton, Charles Swaerd, Karl Swarup, Ghanshyam Sweeney, Sean T. Sylvester, Paul W. Szatmari, Zsuzsanna Szegezdi, Eva Szlosarek, Peter W. Taegtmeyer, Heinrich Tafani, Marco Taillebourg, Emmanuel Tait, Stephen W. G. Takacs-Vellai, Krisztina Takahashi, Yoshinori Takats, Szabolcs Takemura, Genzou Takigawa, Nagio Talbot, Nicholas J. Tamagno, Elena Tamburini, Jerome Tan, Cai-Ping Tan, Lan Tan, Mei Lan Tan, Ming Tan, Yee-Joo Tanaka, Keiji Tanaka, Masaki Tang, Daolin Tang, Dingzhong Tang, Guomei Tanida, Isei Tanji, Kunikazu Tannous, Bakhos A. Tapia, Jose A. Tasset-Cuevas, Inmaculada Tatar, Marc Tavassoly, Iman Tavernarakis, Nektarios Taylor, Allen Taylor, Graham S. Taylor, Gregory A. Taylor, J. Paul Taylor, Mark J. 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[Schwarten, Melanie; Willbold, Dieter] Forschungszentrum Juelich, Struct Biochem ICS 6, Julich, Germany. [Kumar, Rakesh] George Washington Univ, Dept Biochem & Mol Med, Washington, DC USA. [Tavernarakis, Nektarios] Fdn Res & Technol Hellas, Iraklion, Greece. [Ye, Mingxiang; Zhang, Jian] Fourth Mil Med Univ, Dept Biochem & Mol Biol, Xian 710032, Peoples R China. [Wang, Mei-Qing] Fourth Mil Med Univ, Dept Oral Anat & Physiol & TMD, Coll Stomatol, Xian 710032, Peoples R China. [Zhang, Jian] Fourth Mil Med Univ, Dept Pulm Med, Xijing Hosp, Xian 710032, Shaanxi, Peoples R China. [Gutierrez, Maximiliano G.] Francis Crick Inst, Mill Hill Lab, London, England. [Dumit, Veronica I.] Univ Freiburg, Ctr Biol Syst Anal ZBSA, Core Facil Prote, Hugstetter Str 55, D-79106 Freiburg, Germany. [Weindl, Guenther] Free Univ Berlin, Inst Pharm Pharmacol & Toxicol, Berlin, Germany. [Jiang, Yongjun; Liu, Xueqin] Freshwater Aquaculture Collaborat Innovat Ctr Hub, Wuhan, Peoples R China. 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[Krick, Roswitha; Thumm, Michael] Univ Gottingen, Inst Cellular Biochem, D-37073 Gottingen, Germany. [Liotta, Lance A.] George Mason Univ, Manassas, VA USA. [Hawley, Robert G.] George Washington Univ, Dept Anat & Regenerat Biol, Washington, DC USA. [Hawley, Teresa S.] George Washington Univ, Flow Cytometry Core Facil, Washington, DC USA. [Moussa, Charbel E-H] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA. [Clarke, Robert] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. [Suzuki, Yuichiro J.] Georgetown Univ, Dept Physiol & Pharmacol, Washington, DC USA. [Albanese, Chris] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA. [Albanese, Chris] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Pathol, Washington, DC USA. [Avantaggiati, Maria Laura] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Lokeshwar, Bal L.] Georgia Regents Univ, Ctr Canc, Dept Med, Augusta, GA USA. 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[Vandenabeele, Peter] Univ Ghent, Dept Biomed Mol Biol, Inflammat Res Ctr, VIB,Methusalem Program, B-9000 Ghent, Belgium. [Menendez, Javier A.] ICO, Girona Biomed Res Inst IDIBGI, Catalonia, Spain. [Auburger, Georg; Gispert, Suzana; Klinkenberg, Michael] Goethe Univ, Sch Med, Expt Neurol, Frankfurt, Germany. [Doetsch, Volker; Rogov, Vladimir V.] Goethe Univ Frankfurt, Inst Biophys Chem, D-60054 Frankfurt, Germany. [Dikic, Ivan; Grumati, Paolo] Goethe Univ, Sch Med, Inst Biochem 2, Frankfurt, Germany. [Dikic, Ivan; Grumati, Paolo] Buchmann Inst Mol Life, Frankfurt, Germany. [Schaefer, Liliana] Goethe Univ, Inst Pharmacol & Toxicol, Frankfurt, Germany. [Fulda, Simone] Goethe Univ, Inst Expt Canc Res Pediat, Frankfurt, Germany. [Hamann, Andrea; Knuppertz, Laura; Osiewacz, Heinz D.] Goethe Univ, Inst Mol Biosci, Mol Dev Biol, Frankfurt, Hesse, Germany. [Veras, Patricia S. T.] Fundacao Oswaldo Cruz, FIOCRUZ BA, Goncalo Moniz Res Ctr, Lab Pathol & Biointervent, Salvador, BA, Brazil. 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N.] Hannover Med Sch, Dept Clin Immunol & Rheumotol, Hannover, Germany. [Gaestel, Matthias; Menon, Manoj B.] Hannover Med Sch, Dept Biochem, Hannover, Germany. [Thum, Thomas] Hannover Med Sch, Inst Mol & Translat Therapeut Strategies IMTTS, Hannover, Germany. [Bae, Ok-Nam] Hanyang Univ, Coll Pharm, Ansan, South Korea. [Wang, Dong] Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Heilongjiang, Peoples R China. [Xu, Hongwei] Harbin Med Univ, Dept Immunol, Heilongjiang Prov Key Lab Infect & Immun, Harbin, Peoples R China. [Chou, Tsui-Fen] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Chou, Tsui-Fen] Los Angeles Biomed Res Inst, Div Med Genet, Dept Pediat, Torrance, CA USA. [Geng, Jiefei; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Xavier, Ramnik J.] Broad Inst, Boston, MA USA. [Kang, Chanhee] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Genet,Div Genet, Boston, MA 02115 USA. [Kimmelman, Alec C.; Mancias, Joseph D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mancias, Joseph D.] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. [Harper, J. Wade; Yuan, Junying] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Irazoqui, Javier E.] Harvard Univ, Sch Med, Lab Comparat Immunol,Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis,Res Inst, Boston, MA 02115 USA. [Narendra, Derek P.] Harvard Univ, Sch Med, Neurol Residency Program, Brigham & Womens Hosp, Boston, MA 02115 USA. [Narendra, Derek P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Notomi, Shoji; Vavvas, Demetrios G.] Harvard Univ, Sch Med, Ophthalmol, Boston, MA 02115 USA. [Airoldi, Edoardo M.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. [Yuan, Zhi-Min] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Sarrias, Maria Rosa] Hlth Res Inst Germans Trias Pujol, Badalona, Spain. [Abeliovich, Hagai] Hebrew Univ Jerusalem, Fac Agr Food & Environm Biochem & Food Sci, IL-76100 Rehovot, Israel. [Rasse, Tobias M.] Heidelberg Univ, Deutsch Krebsforschungszentrum, Proteostasis Neurodegenerat Dis B180, CHS Res Grp CellNetworks, Heidelberg, Germany. [Schuck, Sebastian] Heidelberg Univ, Zentrum Mol Biol Univ Heidelberg ZMBH, Heidelberg, Germany. [Ventura, Natascia] Univ Dusseldorf, Inst Clin Chem, Dusseldorf, Germany. [Ventura, Natascia] Diagnost Lab, Fac Med, Dusseldorf, Germany. [Willbold, Dieter] Univ Dusseldorf, Inst Phys Biol, Dusseldorf, Germany. [Stork, Bjoern] Univ Dusseldorf, Inst Mol Med, Dusseldorf, Germany. [Schmitz, Ingo] Helmholtz Ctr Infect Res, Syst Oriented Immunol & Inflammat Res, Braunschweig, Germany. [Korhonen, Laura] Univ Helsinki, Cent Hosp, Fac Med, Div Child Psychiat, Helsinki, Finland. [Screen, Mark] Univ Helsinki, Dept Med Genet, Helsinki, Finland. [Zhou, Guang-Zhou] Henan Univ Technol, Coll Bioengn, Zhengzhou 450000, Henan Province, Peoples R China. [Tanji, Kunikazu] Hirosaki Univ, Grad Sch Med, Hirosaki, Aomori, Japan. [Yamada, Takahiro] Hokkaido Univ, Grad Sch Med, Dept Obstet & Gynecol, Sapporo, Hokkaido, Japan. [Kihara, Akio] Hokkaido Univ, Fac Pharmaceut Sci, Kita 12, Sapporo, Hokkaido 060, Japan. [Ubukata, Makoto] Hokkaido Univ, Res Fac Agr, Sapporo, Hokkaido, Japan. [Li, Min; Song, Ju-Xian] Hong Kong Baptist Univ, Sch Chinese Med, Kowloon, Hong Kong, Peoples R China. [Law, Helen Ka-wai; Siu, Parco M.] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Fac Hlth & Social Sci, Kowloon, Hong Kong, Peoples R China. [Ip, Nancy Y.] Hong Kong Univ Sci & Technol, Kowloon, Hong Kong, Peoples R China. [Rautou, Pierre-Emmanuel] Hop Beaujon, Paris, France. [Kroemer, Guido] Hop Europeen Georges Pompidou, AP HP, Paris, France. [Cerella, Claudia; Radogna, Flavia] Hop Kirchberg, Lab Biol Mol & Cellulaire Canc, Luxembourg, Luxembourg. [Lemoine, Antoinette] Hop Univ Paris Sud Biochim & Oncogenet, Hop Paul Brousse, Villejuif, France. [Brumell, John H.] Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. [Mena, Maria A.] Hosp Univ Ramon Cajal, CIBERNED, Dept Neurobiol, Madrid, Spain. [Frigo, Daniel E.] Houston Methodist Res Inst, Genom Med Program, Houston, TX USA. [Kang, Chanhee] Howard Hughes Med Inst, Boston, MA 02115 USA. [Levine, Beth] Howard Hughes Med Inst, Dallas, TX USA. [Yan, Xianghua] Huazhong Agr Univ, Coll Anim Sci & Technol, Wuhan, Hubei, Peoples R China. [Jiang, Yongjun; Liu, Xueqin] Huazhong Agr Univ, Dept Aquat Anim Med, Coll Fisheries, Wuhan, Peoples R China. [Liu, Zexian; Xue, Yu] Huazhong Univ Sci & Technol, Dept Biomed Engn, Coll Life Sci & Technol, Wuhan 430074, Hubei, Peoples R China. [Kaparakis-Liaskos, Maria] Ctr Innate Immun & Infect Dis, Hudson Inst Med Res, Melbourne, Vic, Australia. [Shen, Chiung-Chyi] Hungkuang Univ, Dept Phys Therapy, Taichung, Taiwan. [Aranda, Agustin] Inst Agrochem & Food Technol, IATA CSIC, Paterna, Valencia, Spain. [Menezes, Regina; dos Santos, Claudia Nunes] Inst Biol Expt & Tecnol, iBET, Oeiras, Portugal. [Huang, Yong] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Cederbaum, Arthur I.] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Neurol, Ctr Cognit Hlth, Mt Sinai Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Psychiat, Ctr Cognit Hlth, Mt Sinai Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Yue, Zhenyu] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Wu, Defeng] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Le Cam, Laurent] Inst Rech Cancerol Montpellier, ICM, Montpellier, France. [Pujol, Aurora] ICREA Catalan Inst Res & Adv Studies, Catalonia, Spain. [Vaccari, Thomas] FIRC Inst Mol Oncol, IFOM, Milan, Italy. [Sonawane, Avinash] IIT Univ, Sch Biotechnol, Bhubaneswar, Orissa, India. [Barreiro, Esther] Pompeu Fabra Univ, Barcelona Biomed Res Pk, Dept Resp Med, Lung Canc & Muscle Res Grp,IMIM Hosp Mar CIBERES, Barcelona, Spain. [Thurston, Teresa L. M.] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Mol Bacteriol & Infect, London, England. [Braga, Vania M. M.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [de Belleroche, Jackie] Univ London Imperial Coll Sci Technol & Med, Neurogenet Grp, Div Brain Sci, London, England. [Mostowy, Serge] Univ London Imperial Coll Sci Technol & Med, Microbiol Sect, MRC Ctr Mol Bacteriol & Infect, London, England. [Lee, Michael] Incheon Natl Univ, Div Life Siences, Inchon, South Korea. [Balaji, Kithiganahalli Narayanaswamy] Indian Inst Sci, Dept Microbiol & Cell Biol, Bangalore 560012, Karnataka, India. [Somasundaram, Kumaravel] Indian Inst Sci Microbiol & Cell Biol, Bangalore, Karnataka, India. [Dubey, Vikash Kumar] Indian Inst Technol, Dept Biosci & Bioengn, Gauhati, Assam, India. [Maiti, Tapas K.] Indian Inst Technol, Dept Biotechnol, Kharagpur 721302, W Bengal, India. [Justice, Matthew J.] Indiana Univ Sch Med, Biochem & Mol Biol, Denver, CO USA. [Dong, X. Charlie; Roach, Peter J.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. [Naidu, Samisubbu R.] Indiana Univ Sch Med, Dept Dermatol, Indianapolis, IN 46202 USA. [Broxmeyer, Hal E.] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. [Boulton, Michael E.] Indiana Univ Sch Med, Dept Ophthalmol, Indianapolis, IN 46202 USA. [Khambu, Bilon; Yin, Xiao-Ming] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. [Lahm, Tim] Indiana Univ Sch Med, Richard L Roudebush VA Med Ctr, Div Pulm, Crit Care Sleep & Occupat Med, Indianapolis, IN 46202 USA. [Hong, Yonggeun] Inje Univ, Dept Rehabil Sci, Coll Biomed Sci & Engn, u HARC, Gimhae, South Korea. [Corazzari, Marco] INMI IRCCS L Spallanzani, Rome, Italy. [Bruhat, Alain] Ctr Clermont Theix, INRA, Nutr Humaine UMR 1019, St Genes Champanelle, France. [Favier, Francois B.] INRA, Dynam Musculaire & Metab UMR866, F-34060 Montpellier, France. [Seiliez, Iban] INRA, UR1067, Nutr Metab Aquaculture, St Pee Sur Nivelle, France. [Luciano, Federic] INSERM, U1065, C3M, Team 2, Nice, France. [Belaid, Amine; Brest, Patrick; Mograbi, Baharia] IRCAN, INSERM, U1081, CNRS UMR7284, Nice, France. [Giuliano, Sandy] Ctr Sci Monaco, Biomed Dept, Monaco, Monaco. [Giuliano, Sandy; Pages, Gilles] Univ Nice Sophia Antipolis, Inst Res Canc & Ageing Nice, CNRS UMR 7284, INSERM U1081, F-06189 Nice, France. [Dupuis, Luc] INSERM, U1118, Mecanismes Cent & Periphet Neurodegenerescence, Strasbourg, France. [Kepp, Oliver; Torriglia, Alicia] INSERM, U1138, Paris, France. [Pallet, Nicolas] INSERM, U1147, Paris, France. [Mechta-Grigoriou, Fatima] Inst Curie, INSERM U830, Stress & Canc Lab, Paris, France. [Benard, Giovanni] INSERM U862, Neuroctr Magendie, Bordeaux, France. [Le Cam, Laurent] INSERM U896, Montpellier, France. [Duran, Raul V.; Villar, Victor H.] Univ Bordeaux, INSERM U916, Inst Europeen Chim & Biol, Pessac, France. [Teixeira-Clerc, Fatima] INSERM U955, Fac Med Creteil, UMR S955, Creteil, France. [Laporte, Jocelyn; Nicot, Anne-Sophie] Univ Strasbourg, INSERM U964, CNRS UMR7104, Dept Translat Med,IGBMC, Illkirch Graffenstaden, France. [Andrieu-Abadie, Nathalie] Ctr Rech Cancerol Toulouse, INSERM UMR1037, Toulouse, France. [Dugail, Isabelle] INSERM UMRS 1166, Unite Rech Malad Cardiovasc Metab & Nutr, Paris, France. [Kroemer, Guido] INSERM, Cordeliers Res Canc, Paris, France. [Bulavin, Dmitry V.] INSERM, UMR CNRS 7284 U1081, Nice, France. [Gatti, Evelina; Pierre, Philippe] INSERM, U1104, Marseille, France. [Corti, Olga] INSERM, U1127, CNRS, UMR 7225, Paris, France. 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[Papackova, Zuzana] Inst Clin & Expt Med, Ctr Med Expt, Dept Metab & Diabet, Prague, Czech Republic. [Bianchi, Michele Wolfe] Univ Paris Saclay, Inst Integrat Biol Cell, Gif Sur Yvette, France. [Zorzano, Antonio] Barcelona Inst Sci & Technol, Inst Res Biomed IRB Barcelona, Barcelona, Spain. [Triola, Gemma] Spanish Res Council IQAC CSIC, Inst Adv Chem Catalonia, Dept Biomed Chem, Barcelona, Spain. [Ryabovol, Victoria] Inst Biochem & Biophys, Kazan, Russia. [Almonte-Beceril, Maylin] Inst Biomed Invest INIBIC, Inflamat & Regenerat Med, Coruna, Spain. [Jones, Chris] Inst Canc Res, Div Mol Pathol & Canc Therapeut, London SW3 6JB, England. [Zhivotovsky, Boris] Karolinska Inst, Inst Environm Med, Div Toxicol, Stockholm, Sweden. [Chauhan, Santosh] Inst Life Sci, Bhubaneswar, Odisa, India. [Ishaq, Mohammad] Inst Microbial Technol IMTECH, Cell Biol & Immunol Div, Chandigarh, India. [Vachova, Libuse] Inst Microbiol ASCR, Vvi, Prague, Czech Republic. [Penninger, Josef M.] Austrian Acad Sci, IMBA, Inst Mol Biotechnol, A-1010 Vienna, Austria. [Scovassi, A. Ivana] CNR, Inst Mol Genet, Pavia, Italy. [Stulik, Jiri] FMHS UO, Inst Mol Pathol & Biol, Hradec Kralove, Czech Republic. [Stepkowski, Tomasz M.] Ctr Radiobiol & Biol Dosimetry, Inst Nucl Chem & Technol, Dorodna, Poland. [Vescovi, Eleonora Garcia] Inst Biol Mol & Celular Rosario IBR CONICET, Rosario, Argentina. [Lazo, Pedro A.] Hosp Univ Salamanca, Inst Invest Biomed Salamanca IBSAL, Salamanca, Spain. [Martin-Sanz, Paloma] Ctr Invest Biomed Red Enfermedade Hepat & Digest, Inst Invest Biomed Albert Sols, CSIC UAM, Madrid, Spain. [Valverde, Angela M.] CSIC UAM, Inst Invest Biomed Albert Sols, Madrid, Spain. [Fernandez-Checa, Jose C.] CSIC IDI BAPS, Inst Invest Biomed Barcelona, Barcelona, Spain. [Fernandez-Checa, Jose C.] CIBEREHD, ISCIII, Ctr Invest Red Enfermedades Hepat & Digest, Barcelona, Spain. [Oliver, F. Javier] CSIC, IPBLN, Granada, Spain. [Menezes, Regina; dos Santos, Claudia Nunes] Univ Nova Lisboa, Inst Tecnol Quim & Biol Antonio Xavier, P-2780156 Oeiras, Portugal. [Moita, Luis Ferreira] Inst Gulbenkian Ciencias, Oeiras, Portugal. [Garcia-Ruiz, Carmen] Hosp Clin Barcelona IDIBAPS, Inst Invest Biomed Barcelona IIBB CSIC, Liver Unit, Barcelona, Spain. [Garcia-Ruiz, Carmen] CIBEREHD, Barcelona, Spain. [Wappner, Pablo] Inst Leloir, Buenos Aires, DF, Argentina. [Alonso, Covadonga; Galindo, Inmaculada; Munoz-Moreno, Raquel] Inst Nacl Invest & Tecnol Agr & Alimentaria INIA, Dept Biotecnol, Madrid, Spain. [Perez-de la Cruz, Veronica] Inst Nacl Neurol & Neurocirug, Neurochem Unit, Mexico City, DF, Mexico. [Pineda, Benjamin] Inst Nacl Neurol & Neurocirug, Neuroimmunol & Neuro Oncol Unit, Mexico City, DF, Mexico. [Menna-Barreto, Rubem F. S.] Fiocruz MS, Inst Oswaldo Cruz, Lab Biol Celular, BR-21045900 Rio De Janeiro, Brazil. [Chandra, Pallavi; Kumar, Dhiraj] Int Ctr Genet Engn & Biotechnol, Immunol Grp, New Delhi, India. [Kanthasamy, Anumantha G.] Iowa State Univ, Dept Biomed Sci, Iowa Ctr Adv Neurotoxicl, Ames, IA USA. [Bassham, Diane C.] Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA USA. [MacIntosh, Gustavo C.] Iowa State Univ, Roy J Carver Dept Biochem Biophys & Mol Biol, Ames, IA USA. [Fusco, Carmela; Merla, Giuseppe; Micale, Lucia] IRCCS Casa Sollievo Sofferenza, Med Genet Unit, San Giovanni Rotondo, FG, Italy. [Fornai, Francesco; Sciarretta, Sebastiano] IRCCS Neuromed, Pozzilli, IS, Italy. [Ferraro, Elisabetta] IRCCS San Raffaele Pisana, Lab Skeletal Muscle Dev & Metab, Rome, Italy. [Cecconi, Francesco; D'Amelio, Marcello; Molinari, Marco; Viscomi, Maria Teresa] IRCCS Santa Lucia Fdn, Rome, Italy. [Campello, Silvia] IRCCS Santa Lucia Fdn, Dept Expt Neurosci, Rome, Italy. [Crippa, Valeria] IRCCS C Mondino Natl Neurol Inst, Expt Neurobiol Lab, Pavia, Italy. [Facchiano, Antonio] IRCCS, Ist Dermopatico Immacolata, Rome, Italy. [Cantoni, Lavinia] IRCCS Ist Ric Farmacol Mario Negri, Dept Mol Biochem & Pharmacol, Milan, Italy. [Albani, Diego] IRCCS Ist Ric Farmacol Mario Negri, Dept Neurosci, Milan, Italy. [Matarese, Giuseppe] IRCCS MultiMed, Milan, Italy. [Marin, Concepcio] Inst Invest Biomed August Pi & Sunyer IDIBAPS, IRCE, Barcelona, Spain. [Gongora, Celine] INSERM, IRCM, Inst Rech Cancerol Montpellier, U896, Montpellier, France. [Pattingre, Sophie] IRCM, Inst Rech Cancerol Montpellier, Montpellier, France. [Cottet, Sandra; Schorderet, Daniel F.] IRO, Inst Res Ophthalmol, Sion, Switzerland. [Chiariello, Mario; Colecchia, David] Ist Fisiol Clin, Siena, Italy. [Bachetti, Tiziana; Ceccherini, Isabella] UOC Med Genet, Ist Giannina Gaslini, Genoa, Italy. [Grimaldi, Benedetto] Ist Italiano Tecnol, Dept Drug Discovery & Dev, Lab Mol Med, Genoa, Italy. [Giovannetti, Elisa] Univ Pisa, AIRC Start UP Unit, Canc Pharmacol Lab, Pisa, Italy. [Merlini, Luciano] Ist Ortopedico Rizzoli IOR IRCCS, Lab Musculoskeletal Cell Biol, Bologna, Italy. [Ortona, Elena; Pierdominici, Marina] Ist Super Sanita, Dept Cell Biol & Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy. [Salvioli, Rosa] Ist Super Sanita, Dept Haematol Oncol & Mol Med, Viale Regina Elena 299, I-00161 Rome, Italy. [Coccia, Eliana M.] Ist Super Sanita, Dept Infect Parasit & Immunomediated Dis, Viale Regina Elena 299, I-00161 Rome, Italy. [Matarrese, Paola] Ist Super Sanita, Dept Therapeut Res & Med, Evaluat Sect Cell Aging Degenerat & Gender Med, Viale Regina Elena 299, I-00161 Rome, Italy. [Giammarioli, Anna Maria; Malorni, Walter] Ist Super Sanita, Viale Regina Elena 299, I-00161 Rome, Italy. [Chiariello, Mario; Colecchia, David] Ist Toscano Tumori, Siena, Italy. [Condello, Maria; Meschini, Stefania] Italian Natl Inst Hlth, Dept Technol & Hlth, Rome, Italy. [Schiavi, Alfonso; Ventura, Natascia] IUF Leibniz Res Inst Environm Med, Dusseldorf, Germany. [Stoka, Veronika; Turk, Boris; Turk, Vito] Jozef Stefan Inst, Dept Biochem & Mol & Struct Biol, Ljubljana, Slovenia. [Karmakar, Parimal] Jadavpur Univ, Life Sci & Biotechnol, Kolkata, W Bengal, India. [Gandy, Sam] James J Peters VA Med Ctr, Bronx, NY USA. [Saran, Shweta] Jawaharlal Nehru Univ, Sch Life Sci, New Delhi 110067, India. [Platanias, Leonidas C.] Jesse Brown VA Med Ctr, Dept Med, Chicago, IL USA. [Song, Wei] McGill Univ, Jewish Gen Hosp, Bloomfield Ctr Res Aging, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. [Schipper, Hyman M.] McGill Univ, Jewish Gen Hosp, Dept Neurol & Neurosurg, Dept Med, Montreal, PQ H3T 1E2, Canada. [Topisirovic, Ivan] McGill Univ, Jewish Gen Hosp, Dept Oncol, Montreal, PQ H3T 1E2, Canada. [Yu, Huixin; Zhang, Li] Jiangsu Inst Nucl Med, Wuxi, Jiangsu, Peoples R China. [Su, Zhaoliang] Jiangsu Univ, Dept Immunol, Zhenjiang, Jiangsu, Peoples R China. [Guo, Wenjie] Jiangsu Univ, Sch Pharm, Zhenjiang, Jiangsu, Peoples R China. [Araya, Jun] Jikei Univ, Sch Med, Div Resp Dis, Dept Internal Med, Tokyo, Japan. [Shimada, Yohta] Jikei Univ, Sch Med, Res Ctr Med Sci, Div Gene Therapy, Tokyo, Japan. [Xu, Ye] Jilin Med Univ, Med Res Lab, Jilin, Jilin Province, Peoples R China. [He, Rong-Rong] Jinan Univ, Anti Stress & Hlth Ctr, Coll Pharm, Guangzhou, Guangdong, Peoples R China. [He, Xian-Hui; Ouyang, Dong-yun] Jinan Univ, Dept Immunobiol, Coll Life Sci & Technol, Guangzhou, Guangdong, Peoples R China. [Yang, Xuesong] Jinan Univ, Coll Med, Div Histol & Embryol, Guangzhou, Guangdong, Peoples R China. [Yan, Bo] Jining Med Univ, Shandong Prov Sino US Cooperat Res Ctr Translat M, Jining, Shandong, Peoples R China. [Chen, Gang] Fudan Univ, Jinshan Hosp, Dept Urol, Shanghai 200433, Peoples R China. [Prange, Reinhild] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med Microbiol & Hyg, D-55122 Mainz, Germany. [Kesari, Santosh] John Wayne Canc Inst, Dept Neurosci, Santa Monica, CA USA. [Coppens, Isabelle] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Malaria Res Inst, Dept Mol Microbiol & Immunol, Baltimore, MD 21287 USA. [Ratovitski, Edward A.; Sesaki, Hiromi] Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA. [Wong, G. William] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. [Wong, G. William] Ctr Metab & Obes Res, Baltimore, MD USA. [Dawson, Ted M.] Johns Hopkins Univ Hosp, Sch Med, Dept Neurol Neurosci & Pharmacol, Neuroregenerat Program,Inst Cell Engn, Baltimore, MD 21287 USA. [Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Dept Mol Sci, Neuroregenerat Program,Inst Cell Engn, Baltimore, MD 21287 USA. [Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21287 USA. [Semenza, Gregg L.] McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Dawson, Valina L.] Johns Hopkins Univ Hosp, Sch Med, Neuroregenerat & Stem Cell Programs, Inst Cell Engn,Dept Neurol,Dept Physiol, Baltimore, MD 21287 USA. 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[Kominami, Eiki] Juntendo Univ, Tokyo, Japan. [Hasui, Kazuhisa] Kagoshima Univ, Grad Sch Med & Dent Sci, Div Human Pathol, Dept Oncol,Course Adv Therapeut, Kagoshima 890, Japan. [Setoguchi, Takao] Kagoshima Univ, Near Future Locomoter Organ Med Creat Course, Grad Sch Med & Dent Sci, Kagoshima 890, Japan. [Lee, Gyun Min] Korea Adv Inst Sci & Technol, Dept Biol Sci, Daejon, South Korea. [Okazaki, Toshiro] Kanazawa Med Univ, Dept Med, Kanazawa, Ishikawa, Japan. [Koya, Daisuke] Kanazawa Med Univ, Diabetol & Endocrinol, Kanazawa, Ishikawa, Japan. [Sasaki, Motoko] Kanazawa Univ, Grad Sch Med Sci, Dept Human Pathol, Kanazawa, Ishikawa, Japan. [Wong, Richard W.] Kanagawa Univ, Cell Bion Unit, Dept Biol, Fac Nat Syst,Inst Sci & Engn, Kanagawa, Ishikawa, Japan. [Wong, Richard W.] Kanagawa Univ, Lab Mol & Cellular Biol, Dept Biol, Fac Nat Syst,Inst Sci & Engn, Kanagawa, Ishikawa, Japan. [Lee, Stella Y.; Roelofs, Jeroen] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA. 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[Shintani, Michiko] Kobe Univ, Grad Sch Hlth Sci, Pathol Lab, Div Med Biophys, Kobe, Hyogo, Japan. [Matsushita, Takehiko] Kobe Univ, Grad Sch Med, Dept Orthopaed Surg, Kobe, Hyogo, Japan. [Voitsekhovskaja, Olga V.] Komarov Bot Inst RAS, Plant Ecol Physiol Lab, St Petersburg, Russia. [Cho, Ssang-Goo] Konkuk Univ, Dept Anim Biotechnol, Seoul, South Korea. [Lim, Hyunjung Jade] Konkuk Univ, Dept Vet Med, Seoul, South Korea. [Chung, Hyewon] Konkuk Univ, Sch Med, Dept Ophthalmol, Seoul, South Korea. [Lee, He-Jin] Konkuk Univ, Sch Med, Dept Anat, Seoul, South Korea. [Kim, Cheol Hyeon] Korea Canc Ctr Hosp, Dept Internal Med, Seoul, South Korea. [Lee, Sung-Joon] Korea Univ, Dept Biotechnol, PLUS Grad Sch Life Sci & Biotechnol BK21, Seoul, South Korea. [Chi, Sung-Gil; Choi, Eui-Ju; Lee, Jae Keun; Wright, Karen L.] Korea Univ, Dept Life Sci & Biotechnol, Seoul, South Korea. [Chun, Taehoon] Korea Univ, Dept Biotechnol, Coll Life Sci & Biotechnol, Seoul, South Korea. 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[Ohmuraya, Masaki] Kumamoto Univ, Inst Resource Dev & Anal, Kumamoto, Japan. [Agam, Galila] Kunming Univ Sci & Technol, Sch Med, Kunmimg, Yunnan, Peoples R China. [Tanaka, Masaki; Watanabe, Yoshihisa] Kyoto Prefectural Univ Med, Dept Basic Geriatr, Kyoto, Japan. [Matoba, Satoaki] Kyoto Prefectural Univ Med, Dept Cardiovasc Med, Grad Sch Med Sci, Kyoto, Japan. [Nagata, Kazuhiro] Kyoto Sangyo Univ, Dept Life Sci, Kyoto 603, Japan. [Ushioda, Ryo] Kyoto Sangyo Univ, Dept Mol Biosci, Fac Life Sci, Kyoto 603, Japan. [Goto-Yamada, Shino] Kyoto Univ, Dept Bot, Kyoto, Japan. [Shioi, Tetsuo] Kyoto Univ, Dept Cardiovasc Med, Kyoto, Japan. [Asanuma, Katsuhiko] Kyoto Univ, Grad Sch Med, Med Innocat Ctr TMK Project, Kyoto, Japan. [Cho, Dong-Hyung] Kyung Hee Univ, Grad Sch East Wast Med Sci, Seoul, South Korea. [Bae, Jae-Sung] Kyungpook Natl Univ, Dept Physiol, Sch Med, Daegu, South Korea. [Shirabe, Ken] Kyushu Univ, Dept Surg & Sci, Fukuoka 812, Japan. [Fairlie, W. Douglas; Lee, Erinna F.] Olivia Newton John Canc Res Inst, Melbourne, Vic, Australia. [Soo, Kai Y.] La Trobe Univ, Dept Biochem & Genet, La Trobe Inst Mol Sci, Melbourne, Vic, Australia. [Fairlie, W. Douglas; Lee, Erinna F.] La Trobe Univ, Dept Chem & Phys, Melbourne, Vic, Australia. [Fairlie, W. Douglas; Lee, Erinna F.] La Trobe Univ, Sch Canc Med, Melbourne, Vic, Australia. [Paganetti, Paolo] Neurodegenerat Grp, Lab Biomed Neurosci NSI EOC, Torricella Taverne, Switzerland. [Nilsson, Per] RIKEN, Brain Sci Inst, Lab Proteolyt Neurosci, Wako, Saitama, Japan. [Choi, Eun-Kyoung] Ilsong Inst Life Sci, Lab Cellular Aging & Neurodegenerat, Anyang, Gyeonggi Do, South Korea. [Mayer, Andreas] Univ Lancaster, Fac Hlth & Med, Div Biomed & Life Sci, Lancaster, England. [Erenpreisa, Jekaterina] Latvian Biomed Res & Study Ctr, Riga, Latvia. [Spaink, Herman P.] Leiden Univ, Inst Biol, Leiden, Netherlands. [Stern, Stephan T.] Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick, MD USA. [Los, Marek] Med Univ Silesia, ENT Dept, Sch Med, Katowice, Poland. [Kagedal, Katarina; Mohseni, Simin; Ollinger, Karin] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden. [Kurz, Tino] Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden. [Boman, Andrea] Linkoping Univ, Expt Pathol, Dept Clin & Expt Med, Fac Hlth Sci, Linkoping, Sweden. [Taylor, Mark J.] Univ Liverpool, Liverpool Sch Trop Med, Dept Parasitol, Liverpool L3 5QA, Merseyside, England. [Shajahan-Haq, Ayesha N.] Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Zhivotovsky, Boris] Lomonosov Moscow State Univ, Fac Basic Med, Moscow, Russia. [Tooze, Sharon A.] Canc Res UK, London Res Inst, London, England. [Swanton, Charles] UCL, Inst Canc, London, England. 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[Tan, Mei Lan] Malaysian Inst Pharmaceut & Nutraceuticals, George Town, Malaysia. [Rudolf, Ruediger; Wild, Franziska] Mannheim Univ Appl Sci, Inst Mol & Cell Biol, Mannheim, Germany. [Slaninova, Iva] Masaryk Univ, Dept Biol, Fac Med, Brno, Czech Republic. [Costes, Safia; Mao, Kai] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Costes, Safia] Harvard Univ, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Costes, Safia] Dept Neurol, Boston, MA USA. [Goruppi, Sandro; Lee, Sam W.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Charlestown, MA USA. [Goruppi, Sandro; Lee, Sam W.] Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Mao, Kai] Harvard Univ, Sch Med, Dept Mol Biol, Dept Genet, Boston, MA 02115 USA. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Expt Therapeut & Mol Imaging Lab, Neurosci Ctr, Charlestown, MA USA. [Vyas, Jatin M.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. 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[Yamanaka, Koji] Nagoya Univ, Environm Med Res Inst, Nagoya, Aichi 4648601, Japan. [Fei, Erkang] Nanchang Univ, Inst Life Sci, Nanchang, Peoples R China. [Dai, Chunsun] Nanjing Med Univ, Ctr Kidney Dis, Affiliated Hosp 2, Nanjing, Jiangsu, Peoples R China. [Jiang, Teng] Nanjing Med Univ, Dept Neurol, Nanjing Hosp 1, Nanjing, Jiangsu, Peoples R China. [Liu, Xinfeng] Nanjing Univ, Sch Med, Jinling Hosp, Dept Neurol, Nanjing 210008, Jiangsu, Peoples R China. [Wei, Jiwu] Nanjing Univ, Jiangsu Key Lab Mol Med, Sch Med, Nanjing 210008, Jiangsu, Peoples R China. [Wei, Jiwu] State Key Lab Pharmaceut Biotechnol, Nanjing, Jiangsu, Peoples R China. [Sun, Yang] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210008, Jiangsu, Peoples R China. [Gong, Qingqiu] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China. [Wong, Esther] Nanyang Technol Univ, Sch Biol Sci, Singapore 639798, Singapore. [Shibuya, Kenichi] NARO Inst Floricultural Sci, Tsukuba, Ibaraki, Japan. [Dmytruk, Kostyantyn] NAS Ukraine, Dept Mol Genet & Biotechnol, Inst Cell Biol, Lvov, Ukraine. [Tchetina, Elena V.] Nasonova Res Inst, Rheumatol Immunol & Mol Biol Lab, Moscow, Russia. [Sibirny, Andriy A.] Natl Acad Sci Ukraine, Dept Biotechnol & Microbiol, Lvov, Ukraine. [Papassideri, Issidora; Stravopodis, Dimitrios J.] Univ Athens, Dept Cell Biol & Biophys, Fac Biol, Athens 11528, Greece. [Jana, Nihar Ranjan] Natl Brain Res Ctr, Manesar, Gurgaon, India. [Kim, Soo-Youl] Natl Canc Ctr, Canc Cell & Mol Biol Branch, Div Canc Biol, Res Inst, Goyang, South Korea. [Cheong, Heesun] Natl Canc Ctr, Div Canc Biol, Res Inst, Gyeonggi, South Korea. [Nagai, Yoshitaka] Natl Ctr Neurol & Psychiat, Dept Degenerat Neurol Dis, Kodaira, Tokyo, Japan. [Nishino, Ichizo] Natl Ctr Neurol & Psychiat, Dept Neuromuscular Res, Natl Inst Neurosci, Tokyo, Japan. [Cheung, Chun Hei Antonio] Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 701, Taiwan. 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[Salomoni, Paolo] UCL Canc Inst, Samantha Dickson Brain Canc Unit, London, England. [Jacques, Thomas S.] UCL Inst Child Hlth, London, England. [Jacques, Thomas S.] Great Ormond St Hosp Children NHS Fdn Trust, London, England. [Lewis, Patrick A.] UCL Inst Neurol, Dept Mol Neurosci, London, England. [Manzoni, Claudia] UCL Inst Neurol, London, England. [Cheetham, Michael E.] UCL Inst Ophthalmol, London, England. [Guo, Ming] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. [Linden, Rafael] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Rio de Janeiro, Brazil. [Simmet, Thomas] Univ Ulm, Inst Pharmacol Nat Cpds & Clin Pharmacol, D-89069 Ulm, Germany. [Carlsson, Sven R.] Umea Univ, Dept Med Biochem & Biophys, Umea, Sweden. [Kaeffer, Bertrand] UMR 1280, Nantes, France. [Manie, Serge N.] CNRS, INSERM 1052, UMR 5286, Canc Res Ctr Lyon, Lyon, France. [Maiuri, Maria Chiara] Ctr Rech Cordeliers, UMRS 1138, Paris, France. [Gorbunov, Nikolai V.] Uniformed Serv Univ Hlth Sci, Dept Anesthesiol, Bethesda, MD 20814 USA. [Kiang, Juliann G.] Uniformed Serv Univ Hlth Sci, Radiat Combined Injury Program, Armed Forces Radiobiol Res Inst, Bethesda, MD 20814 USA. [Ozpolat, Bulent; Scovassi, A. Ivana; Stellrecht, Christine M.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Gonzalez, Carlos B.] Univ Austral Chile, Dept Physiol, Valdivia, Chile. [Diaz-Nido, Javier] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CIBERER, Madrid, Spain. [Gargini, Ricardo] Univ Autonoma Madrid, CNB CSIC, Ctr Biol Mol Severo Ochoa, Dept Biol Mol, Madrid, Spain. [Cuezva, Jose M.] Univ Autonoma Madrid, Dept Biol Mol, Madrid, Spain. [Magarinos, Marta] Univ Autonoma Madrid, Dept Biol, Madrid, Spain. [Guillen, Carlos] Univ Complutense, Sch Pharm, E-28040 Madrid, Spain. [Guillen, Carlos] Inst Salud Carlos III, CIBER Diabet & Enfermedades Metab Olicas Asociada, Madrid, Spain. [Papademetrio, Daniela L.] Univ Buenos Aires, Inmunol, Fac Farm & Bioquim, Buenos Aires, DF, Argentina. [Cena, Valentin] Univ Castilla La Mancha, Albacete, Spain. [Jordan, Joaquin] Univ Castilla La Mancha, Fac Med, Dept Ciencias Med, Albacete, Spain. [Sanchez-Prieto, Ricardo] Univ Castilla La Mancha, Lab Oncol Mol, Ctr Reg Invest Biomed, Albacete, Spain. [Troncoso, Rodrigo] Univ Chile, Adv Ctr Chron Dis ACCDiS, Fac Ciencias Quim & Farmaceut, Santiago, Chile. [Chiong, Mario; Criollo, Alfredo; Lavandero, Sergio] Univ Chile, Adv Ctr Chron Dis ACCDiS, Santiago, Chile. [Diaz-Araya, Guillermo] Univ Chile, Fac Ciencias Quim & Farmaceut, Santiago, Chile. [Glavic, Alvaro] Univ Chile, Fac Ciencias, Dept Biol, Ctr Regulac Genoma, Santiago, Chile. [Troncoso, Rodrigo] Univ Chile, INTA, Santiago, Chile. [Corral-Ramos, Cristina; Di Pietro, Antonio; Roncero, M. Isabel G.; Ruiz-Roldan, Carmen] Univ Cordoba, Campus Excelencia Agroalimentario CeiA3, Dept Genet, Cordoba, Spain. [Mora-Rodriguez, Rodrigo] Univ Costa Rica, CIET, San Jose, Costa Rica. [Fuentes, Jose M.; Gomez-Sanchez, Ruben; Ana Gonzalez-Polo, Rosa; Niso-Santano, Mireia] Univ Extremadura, CIBERNED, Dept Bioquim & Biol Mol & Genent, Fac Enfermeria & Terapia Ocupac, Caceres, Spain. [Fernandez-Lopez, Arsenio; Perez-Rodriguez, Diego] Univ Leon, Area Biol Celular, Inst Biomed, E-24071 Leon, Spain. [Fernandez-Barrena, Maite G.] Univ Navarra, Ctr Invest Med Aplicada, E-31080 Pamplona, Spain. [Albaiceta, Guillermo M.] Univ Oviedo, Dept Biol Func, Oviedo, Spain. [Fernandez, Alvaro F.; Lopez-Otin, Carlos] Univ Oviedo, Inst Univ Oncol, Dept Bioquim & Biol Mol, Oviedo, Spain. [Jimenez, Alberto] Univ Salamanca, Dept Microbiol & Genet, Campus Miguel Unamuno, E-37008 Salamanca, Spain. [Boada-Romero, Emilio; Pimentel-Muinos, Felipe X.] Univ Salamanca, IBMCC, Ctr Invest Canc, Campus Unamuno, Salamanca, Spain. [Miranda-Vizuete, Antonio] Univ Seville, Inst Biomed Sevilla, Hosp Univ Virgen Rocio, Consejo Super Invest Cient, Seville, Spain. [Ruano, Diego] Univ Seville, Inst Biomed Sevilla, Seville, Spain. [Crespo, Jose L.; Esther Perez-Perez, Maria] Univ Seville, CSIC, Inst Bioquim Vegetal & Fotosintesis, Seville, Spain. [Couve, Eduardo] Univ Valparaiso, Inst Biol, Fac Ciencias, Valparaiso, Chile. [Pardo, Julian] Univ Zaragoza Araid, IIS Aragon, Ctr Invest Biomed Aragon, Zaragoza, Spain. [Filippi-Chiela, Eduardo C.; Lenz, Guido; Thome, Marcos P.] Univ Fed Rio Grande do Sul, Dept Biophys, Porto Alegre, RS, Brazil. [Filippi-Chiela, Eduardo C.; Lenz, Guido; Thome, Marcos P.] Ctr Biotechnol, Porto Alegre, RS, Brazil. [Silvia Romano, Patricia] Univ Nacl Cuyo FCM UNCUYO, Inst Histol & Embriol IHEM CONICET, Fac Ciencias Med, Mendoza, Argentina. [Sanchez-Alcazar, Jose A.] Univ Pablo Olavide, CABD, Consejo Super Invest Cient Junta Andalucia, Seville, Spain. [Weis, Simone Nardin] Univ Brasilia, Dept Biol Celular, Brasilia, DF, Brazil. [Rodrigues, Cecilia M. P.] Univ Lisbon, Res Inst Med iMed ULisboa, Fac Pharm, Lisbon, Portugal. [Botana, Luis M.] Univ Santiago Compostela, Dept Farmacol, Fac Vet, Lugo, Spain. [Goldman, Gustavo H.] Univ Sao Paulo, FCFRP, USP, Sao Paulo, Brazil. [Hernandez, Agustin] Univ Sao Paulo, Dept Parasitol, Inst Ciencias Biomed, Sao Paulo, Brazil. [Brito, Glauber C.] Univ Sao Paulo, Inst Canc Estado Sao Paulo, Fac Med, Sao Paulo, SP, Brazil. [Tenorio de Melo, Edesio Jose] Univ Estadual Norte Fluminense, Ctr Biociencias Biotecnol, Lab Biol Celular & Tecidual, Setor Toxicol Celular, Campos Goytacazes, Rio De Janeiro, Brazil. [Rizzo, Elizete] Univ Fed Minas Gerais, Dept Morfol, Inst Ciencias Biol, Belo Horizonte, MG, Brazil. [Bincoletto, Claudia] Univ Fed Sao Paulo UNIFESP, Dept Farmacol, Escola Paulista Med, Sao Paulo, SP, Brazil. [Vieira, Helena L. A.] Univ Nova Lisboa, CEDOC, NOVA Med Sch, Lisbon, Portugal. [Revuelta, Jose L.] Univ Salamanca, Dept Microbiol & Genet, Campus Miguel Unamuno, E-37008 Salamanca, Spain. [Poletti, Angelo; Rusmini, Paola] Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy. [Carra, Serena] Univ Modena & Reggio Emilia, Dipartimento Sci Biomed Metab & Neurosci, Modena, Italy. [Follo, Carlo; Isidoro, Ciro] Univ Piemonte Orientale, Dipartimento Sci Salute, Novara, Italy. [Genazzani, Armando A.] Univ Piemonte Orientale, Novara, Italy. [Matarese, Giuseppe] Univ Salerno, Dipartimento Med & Chirurg, I-84100 Salerno, Italy. [Rippo, Maria Rita] Univ Politecn Marche, Dept Clin & Mol Sci, Ancona, Italy. [Cenci, Simone; Milan, Enrico] Univ Vita Salute San Raffaele, Milan, Italy. [Casas, Caty] Univ Autonoma Barcelona, Dept Cell Biol Physiol & Immunol, Inst Neurociencies, E-08193 Barcelona, Spain. [Ventura, Salvador] Autonomous Univ Barcelona, Inst Biotecnol & Biomed, Bellaterra, Barcelona, Spain. [Ventura, Salvador] Dept Bioquim & Biol Mol, Bellaterra, Barcelona, Spain. [Zorzano, Antonio] Univ Barcelona, Dept Bioquim & Biol Mol, Fac Biol, Barcelona, Spain. [Luis Rosa, Jose] Univ Barcelona, Hosp Llobregat, Dept Ciencies Fisiol Giques 2, Inst Invest Biomed Bellvitge IDI BELL, Campus Bellvitge, Barcelona, Spain. [Segui-Simarro, Jose M.] Univ Politecn Valencia, COMAV Inst, E-46022 Valencia, Spain. [Reichert, Andreas S.] Univ Klinikum Dusseldorf, Inst Biochem & Mol Biol 1, Dusseldorf, Germany. [Bouchecareilh, Marion; Priault, Muriel] Univ Bordeaux Segalen, Inst Biochim & Genet Cellulaires, CNRS, UMR 5095, Bordeaux, France. [Pasquet, Jean-Max] Univ Bordeaux Segalen, INSERM U1035, Hematopoiese Leucem & Cibles Therapeut, Bordeaux, France. [Duvezin-Caubet, Stephane] Univ Bordeaux, Inst Biochim & Genet Cellulaires, CNRS, UMR 5095, Bordeaux, France. [Lapaquette, Pierre] Univ Bourgogne Franche Comte, Agrosup Dijon, UMR PAM, Equipe Vin Aliment Microbiol, Dijon, France. [Feron, Olivier] Catholic Univ Louvain, IREC, B-1200 Brussels, Belgium. [Batoko, Henri] Catholic Univ Louvain, Inst Sci Vie, Louvain La Neuve, Belgium. [Deldicque, Louise] Catholic Univ Louvain, Inst Neurosci, Louvain La Neuve, Belgium. [Gailly, Philippe] Catholic Univ Louvain, Lab Cell Physiol, B-1200 Brussels, Belgium. [Bruhat, Alain] Univ Clermont 1, UFR Med, Nutr Humaine UMR1019, Clermont Ferrand, France. [Dalmasso, Guillaume; Darfeuille-Michaud, Arlette; Nguyen, Hang T. T.] Univ Auvergne, M2iSH, INSERM UMR 1071, Ctr Biomed Rech & Valorisat,Fac Med, Clermont Ferrand, France. [Djavaheri-Mergny, Mojgan] Univ Bordeaux, INSERM U916, Inst Bergonie, Bordeaux, France. [Dehay, Benjamin] Univ Bordeaux, Inst Malad Neurodegenerat, CNRS UMR 5293, Bordeaux, France. [Camougrand, Nadine] Univ Bordeaux, CNRS, Inst Biochim & Genet Cellulaires, UMR 5095, Bordeaux, France. [Delage-Mourroux, Regis] Univ Franche Comte, UFR Sci & Tech EA3922, SFR IBCT FED 4234, Estrogenes Express Genique & Pathol Syst Nerveux, Besancon, France. [Boyer-Guittaut, Michaeel] Univ Franche Comte, UFR Sci & Tech, Lab Biochim, Besancon, France. [Verdier, Mireille] Univ Limoges, EA 3842, LHCP, Fac Med, Limoges, France. [Kretz-Remy, Carole] Univ Lyon, Lyon, France. [Kretz-Remy, Carole] Univ Lyon 1, Ctr Genet & Physiol Mol & Cellulaire, F-69622 Villeurbanne, France. [Freyssenet, Damien G.] Univ Lyon, Fac Med, Saint Etienne, France. [Faure, Mathias] Univ Lyon, INSERM, CIRI, Ecole Normale Super Lyon,CNRS,UMR 5308,U 111, Lyon, France. [Mollereau, Bertrand] Univ Lyon, CNRS UMR 5239, Mol Cell Biol Lab, Ecole Normale Super Lyon, Lyon, France. [Besteiro, Sebastien] Univ Montpellier, DIMNP, CNRS, UMR 5235, F-34059 Montpellier, France. [Pattingre, Sophie] Univ Montpellier, Inst Reg Canc Montpellier, INSERM, U 1194, F-34059 Montpellier, France. [Favier, Francois B.] Univ Montpellier, F-34059 Montpellier, France. [Bernard, Monique; Hebert, Marie-Josee] Univ Montreal, Dept Med, Montreal, PQ, Canada. [Pacelli, Consiglia] Univ Montreal, Dept Pharmacol, Fac Med, Montreal, PQ H3C 3J7, Canada. [Burelle, Yan] Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7, Canada. [Knaevelsrud, Helene] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada. [Vallette, Francois] Univ Nantes, CRCNA, UMRINSERM 892, CNRS 6299, Nantes, France. [Chevet, Eric] Univ Rennes 1, OSS, ERL INSERM 440, Ctr Lutte Canc Eugene Marquis, Rennes, France. [Beaulieu, Jean-Francois; Jean, Steve] Univ Sherbrooke, Dept Anat & Cell Biol, Fac Med & Hlth Sci, Sherbrooke, PQ J1K 2R1, Canada. [Dupuis, Luc] Univ Strasbourg, Fac Med, UMRS 1118, Strasbourg, France. [Gros, Frederic] Univ Strasbourg, CNRS UPR3572, Immunopathol & Chim Therapeut, IBMC, Strasbourg, France. [Barbeau, Benoit] Univ Quebec, Dept Sci Biol, Montreal, PQ H3C 3P8, Canada. [Barbeau, Benoit] Ctr Rech BioMed, Montreal, PQ, Canada. [Taillebourg, Emmanuel] Univ Grenoble Alpes, CEA DSV iRTSV BGE GenandChem, INSERM, U1038, Grenoble, France. [Francois, Arnaud] Univ Laval, Neurosci Axis, Quebec City, PQ, Canada. [Cnop, Miriam] Univ Libre Bruxelles, ULB Ctr Diabet Res, Brussels, Belgium. [Palladino, Francesca] Univ Lyon, Ecole Normale Super Lyon, Lyon, France. [Baghdiguian, Stephen] Univ Montpellier 2, Inst Sci Evolut, CNRS, UMR 5554, Montpellier, Languedoc Rouss, France. [Pierrefite-Carle, Valerie] Univ Nice Sophia Antipolis, UMR MATOs CEA iBEB E 4320TIRO, Fac Med, Nice, France. [Kroemer, Guido] Univ Paris 05, Apoptosis Canc & Immun Lab, Team 11, Equipe Labellisee Ligue Canc & Cell Biol & Met Pl, Paris, France. [Tamburini, Jerome] Univ Paris 05, Inst Cochin, Sorbonne Paris Cite, Fac Med, Paris, France. [Pende, Mario] Univ Paris 05, Inst Necker Enfants Malades, INSERM, U1151, Paris, France. [Rautou, Pierre-Emmanuel] Univ Paris 05, Paris, France. [Bravo-San Pedro, Jose M.; Galluzzi, Lorenzo; Izzo, Valentina; Pietrocola, Federico; Sica, Valentina] Univ Paris Descartes Paris V, Paris, France. [Botti, Joelle; Codogno, Patrice; Dupont, Nicolas; Hamai, Ahmed; Mehrpour, Maryam; Morel, Etienne; Nascimbeni, Anna Chiara; Orhon, Idil] Univ Paris 05, Sorbonne Paris Cite, INEM, INSERM U1151,CNRS UMR 5253, Paris, France. [Ait-Si-Ali, Slimane] Univ Paris 05, Sorbonne Paris Cite, Ctr Epigenet & Destin Cellulaire, CNRS,UMR 7216, Paris, France. [Le Stunff, Herve] Univ Paris 05, Unite Biol Fonctionnelle & Adaptat, CNRS UMR 8251, Paris, France. [Bianchi, Michele Wolfe] Univ Paris Est Creteil, Creteil, France. [Teixeira-Clerc, Fatima] Univ Paris Est, Inst Mondor Rech Biomed, Paris, France. [Le Stunff, Herve; Legouis, Renaud] Univ Paris Sud, CEA, CNRS, Inst Integrat Biol Cell, Gif Sur Yvette, France. [Bianchi, Michele Wolfe] Univ Paris Sud, CEA, CNRS, Paris, France. [Deutsch, Eric] Univ Paris Sud, INSERM 1030, Gustave Roussy Canc Campus, Paris, France. [Dokudovskaya, Svetlana] Univ Paris Sud, Inst Gustave Roussy, CNRS UMR 8126, Villejuif, France. [Wiels, Joelle] Univ Paris Sud, Univ Paris Saclay, CNRS UMR 8126, Inst Gustave Roussy, Villejuif, France. [Tan, Mei Lan] Univ Sains Malaysia, Adv Med & Dent Inst, Minist Sci Technol & Innovat, George Town, Malaysia. [D'Orazi, Gabriella] Univ G dAnnunzio, Dept Med Oral & Biotechnol Sci, Chieti, Italy. [Corasaniti, Maria Tiziana] Magna Graecia Univ Catanzaro, Dept Hlth Sci, Catanzaro, Italy. [Isakovic, Aleksandra J.] Univ Belgrade, Sch Med, Belgrade, Serbia. [Lizard, Gerard] Univ Bourgogne Franche Comte, EA 7270, INSERM, Dijon, France. [Fortunato, Franco] Univ Clin Heidelberg, Dept Expt Surg, Heidelberg, Germany. [Rami, Abdelhaq] Univ Clin, Inst Cellular & Mol Anat Anat 3, Frankfurt, Germany. [McKenna, Sharon; O'Donovan, Tracey] Natl Univ Ireland Univ Coll Cork, BioSci Inst Co, Cork Canc Res Ctr, Cork, Ireland. [Waeber, Christian] Natl Univ Ireland Univ Coll Cork, Sch Pharm, Dept Pharmacol & Therapeut, Cork, Ireland. [Al-Rubeai, Mohamed] Univ Coll Dublin, Sch Chem & Bioproc Engn, Dublin 2, Ireland. [Alvarez-Erviti, Lydia; Cooper, J. Mark] UCL, Dept Clin Neurosci, London, England. [Ketteler, Robin; Kriston-Vizi, Janos; Prak, Krisna] UCL, MRC Lab Mol Cell Biol, London, England. [Duchen, Michael R.] UCL, UCL Consortium Mitochondrial Res, London, England. [Duchen, Michael R.] Dept Cell & Dev Biol, London, England. [Clementi, Emilio] Univ Milan, Univ Hosp Luigi Sacco, Clin Pharmacol Unit, Natl Res Council,Inst Neurosci,Dept Biomed & Clin, Milan, Italy. [Strnad, Pavel] Univ Hosp Aachen, IZKF, Aachen, Germany. [Strnad, Pavel] Dept Internal Med III, Aachen, Germany. [Puyal, Julien; Truttmann, Anita C.] Univ Lausanne, Univ Hosp Ctr, Clin Neonatol, Dept Pediat & Pediat Surg, Lausanne, Switzerland. [Bergami, Matteo] Univ Hosp Cologne, CECAD Res Ctr, Cologne, Germany. [Klucken, Jochen; Minakaki, Georgia] Univ Erlangen Nurnberg, Univ Hosp Erlangen, D-91054 Erlangen, Germany. [Hasselblatt, Peter] Univ Hosp Freiburg, Dept Med 2, Freiburg, Germany. [Dahmen, Uta] Univ Hosp Jena, Dept Gen Visceral & Vasc Surg, Expt Transplantat Surg, Jena, Germany. [Bou, German] Univ Hosp La Coruna, Dept Microbiol, La Coruna, Spain. [Pavenstaedt, Hermann] Univ Hosp Muenster, Internal Med D, Dept Nephrol Hypertens & Rheumatol, Albert Schweitzer Campus, Munster, Germany. [Patschan, Daniel] Univ Hosp Gottingen, Dept Nephrol & Rheumatol, Gottingen, Germany. [Duchosal, Michel A.] Univ Hosp Lausanne, Serv & Cent Lab Hematol, Lausanne, Switzerland. [Weide, Thomas] Univ Hosp Muenster, Dept Internal Med D, Mol Nephrol, Munster, Germany. [Schneider, E. Marion] Univ Hosp Ulm, Sekt Expt Anaestesiol, Ulm, Germany. [Scharl, Michael] Univ Hosp Zurich, Div Gastroenterol & Hepatolog, Zurich, Switzerland. [Decuypere, Jean-Paul] Univ Hosp Leuven, Dept Microbiol & Immunol, Lab Abdominal Transplantat, Leuven, Belgium. [Vandenberghe, Wim] Univ Hosp Leuven, Dept Neurol, Leuven, Belgium. [Martinez, Jennifer] Natl Inst Environm Hlth Sci, Immun Inflammat & Dis Lab, Res Triangle Pk, NC USA. [Duez, Helene; Lancel, Steve] Univ Lille, INSERM, CHU Lille, Inst Pasteur Lille,U1011,EGID, Lille, France. [Huber, Tobias B.] Univ Med Ctr Freiburg, Freiburg, Germany. [Vellenga, Edo] Univ Groningen, Univ Med Ctr Groningen, Dept Hematol, Groningen, Netherlands. [Galliciotti, Giovanna] Univ Hamburg, Med Ctr, Inst Neuropathol, Hamburg, Germany. [Behl, Christian] Johannes Gutenberg Univ Mainz, Med Ctr, Inst Pathobiochemi, D-55122 Mainz, Germany. [Mari, Muriel; Reggiori, Fulvio] Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Groningen, Netherlands. [Schmidt, Jens] Univ Gottingen, Med Ctr, Clin Neurol, D-37073 Gottingen, Germany. [Schmidt, Jens] Dept Neuroimmunol, Gottingen, Germany. [Outeiro, Tiago F.] Univ Gottingen, Med Ctr, Dept Neurodegenerat & Restorat Res, D-37073 Gottingen, Germany. [Boes, Marianne] Univ Utrecht, Med Ctr, Lab Translat Immunol, Utrecht, Netherlands. [Boes, Marianne] Univ Hosp Children & Youth, Dept Pediat Immunol, Utrecht, Netherlands. [Koch, Jan C.] Univ Med Gottingen, Dept Neurol, Gottingen, Germany. [Wang, Jing] Univ Montpellier I, INSERM U1051, Montpellier, France. [Vidal, Michel] Univ Montpellier, UMR5235, F-34059 Montpellier, France. [Coxon, Fraser P.] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland. [Ganesan, Swamynathan] Univ Adelaide, Alzheimers Dis Genet Lab, Adelaide, SA, Australia. [Richards, Robert I.] Univ Adelaide, Dept Genet & Evolut, Sch Biol Sci, Adelaide, SA, Australia. [Ramanadham, Sasanka] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol CDIB, Comprehens Diabet Ctr UCDC, Birmingham, AL USA. [Xu, Zhi-Xiang] Univ Alabama Birmingham, Dept Med, Div Hematol & Oncol, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Roth, Kevin A.; Shacka, John J.; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Darley-Usmar, Victor M.] Univ Alabama Birmingham, Dept Pathol, Ctr Free Radical Biol, Birmingham, AL 35294 USA. [Chatham, John C.] Univ Alabama Birmingham, Div Mol & Cellular Pathol, Dept Pathol, Birmingham, AL USA. [Kim, Yonghyun] Univ Alabama, Dept Chem & Biol Engn, Tuscaloosa, AL USA. [Goping, Ing Swie] Univ Alberta, Dept Biochem, Edmonton, AB, Canada. [Diaz-Laviada, Ines] Univ Alcala De Henares, Dept Syst Biol, Biochem & Mol Biol Unit, Sch Med, Madrid, Spain. [Medema, Jan Paul] Univ Amsterdam, Acad Med Ctr, Lab Expt Oncol & Radiobiol, Meibergdreef 9, NL-1105 AZ Amsterdam, North Holland, Netherlands. [Juenemann, Katrin] Univ Amsterdam, Acad Med Ctr, Dept Cellbiol & Histol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Meijer, Alfred J.] Univ Amsterdam, Acad Med Ctr, Dept Med Biochem, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Berkhout, Ben] Univ Amsterdam, Acad Med Ctr, Lab Expt Virol, Ctr Infect & Immun Amsterdam CINIMA, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Norga, Koenraad K.] Univ Antwerp, Dept Paediat Oncol, B-2020 Antwerp, Belgium. [De Meyer, Guido R. Y.; Martinet, Wim] Univ Antwerp, Lab Physiopharmacol, B-2020 Antwerp, Belgium. [Landowski, Terry H.] Univ Arizona, Ctr Canc, Dept Med, Tucson, AZ USA. [Kruer, Michael C.] Univ Arizona, Coll Med, Barrow Neurol Inst, Phoenix Childrens Hosp,Dept Child Hlth, Phoenix, AZ USA. [Riehle, Michael A.] Univ Arizona, Dept Entomol, Tucson, AZ USA. [Chen, Yin; Klimecki, Walter T.; Zhang, Donna D.] Univ Arizona, Dept Pharmacol & Toxicol, Coll Pharm, Tucson, AZ 85721 USA. [Ding, Zufeng; Mehta, Jawahar L.] Univ Arkansas Med Sci, Dept Cardiol, Little Rock, AR 72205 USA. [Voth, Daniel E.] Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. [MacMillan-Crow, Lee Ann; Parajuli, Nirmala] Univ Arkansas Med Sci, Dept Pharmacol Toxicol, Little Rock, AR 72205 USA. [Dridi, Sami] Univ Arkansas, Ctr Excellence Poultry Sci, Fayetteville, AR 72701 USA. [Konstantakou, Eumorphia G.; Stravopodis, Dimitrios J.; Trougakos, Ioannis P.; Velentzas, Athanassios D.] Univ Athens, Dept Cell Biol & Biophys, Fac Biol, Athens, Greece. [Mpakou, Vassiliki E.] Univ Athens, Sch Med, Dept Internal Med 2, Athens, Greece. [Mpakou, Vassiliki E.] Attikon Univ, Gen Hosp, Res Inst, Athens, Greece. [Kampinga, Harm H.] Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Groningen, Netherlands. [Pierre, Philippe] Univ Aveiro, Inst Res Biomed iBiMED, Aveiro Hlth Sci Program, Aveiro, Portugal. [Neves, Bruno M.] Univ Aveiro QOPNA, Dept Chem, Aveiro, Portugal. [Claria, Joan; Lopez-Vicario, Cristina] Univ Barcelona, Dept Biochem & Mol Genet, Hosp Clin, IDIBAPS CIBERehd, Barcelona, Spain. [Ambrosio, Santiago] Univ Barcelona, Sch Med, Campus Bellvitge, Lhospitalet De Llobregat, Spain. [Cocco, Tiziana] Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Organs Senses, Bari, Italy. [Tucci, Marco] Univ Bari Aldo Moro, Dept Biomed Sci & Clin Oncol, Bari, Italy. [Simone, Cristiano] Univ Bari Aldo Moro, Div Med Genet, DIMO, Sch Med, Bari, Italy. [Castets, Perrine; Ruegg, Markus A.; Spang, Anne] Univ Basel, Biozentrum, Basel, BS, Switzerland. [Boeckler, Stefan; Westermann, Benedikt] Univ Bayreuth, Cell Biol, Bayreuth, Germany. [Steegborn, Clemens] Univ Bayreuth, Dept Biochem, Bayreuth, Germany. [Harhaji-Trajkovic, Ljubica] Univ Belgrade, Inst Biol Res Sinisa Stankov, Belgrade, Serbia. [Kravic-Stevovic, Tamara] Univ Belgrade, Inst Histol & Embryol, Sch Med, Belgrade, Serbia. [Markovic, Ivanka] Univ Belgrade, Inst Med & Clin Biochem, Fac Med, Belgrade, Serbia. [Trajkovic, Vladimir] Univ Belgrade, Sch Med, Belgrade, Serbia. [Bumbasirevic, Vladimir] Univ Belgrade, Sch Med, Inst Histol & Embryol, Belgrade, Serbia. [Tschan, Mario P.] Univ Bern, Div Expt Pathol, Inst Pathol, Bern, Switzerland. [Arcaro, Alexandre] Univ Bern, Div Pediat Hematol Oncol, Dept Clin Res, Bern, Switzerland. [Buetikofer, Peter] Univ Bern, Inst Biochem & Mol Med, Bern, Switzerland. [Simon, Hans-Uwe] Univ Bern, Inst Pharmacol, Bern, Switzerland. [Sarkar, Sovan; Ward, Carl] Univ Birmingham, Inst Biomed Res, Inst Canc & Genom Sci, Coll Med & Dent Sci, Birmingham, W Midlands, England. [Taylor, Graham S.] Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham, W Midlands, England. [Martelli, Alberto M.] Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy. [Cetrullo, Silvia; Flamigni, Flavio] Univ Bologna, Dipartimento Sci Biomed & Neuromotorie, Bologna, Italy. [Walter, Jochen] Univ Bonn, Dept Neurol, Bonn, Germany. [Haas, Albert; Hoehfeld, Joerg] Univ Bonn, Inst Cell Biol, Bonn, Germany. [Till, Andreas] Univ Bonn, Inst Reconstruct Neurobiol, Bonn, Germany. [Fanzani, Alessandro] Univ Brescia, Dept Mol & Translat Med, Brescia, Italy. [Lane, Jon D.] Univ Bristol, Sch Biochem, Bristol, Avon, England. [Greenhough, Alexander] Univ Bristol, Sch Cellular & Mol Med, Bristol, Avon, England. [Roberge, Michel; Yip, Calvin K.] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada. [Johnson, James D.; Nabi, Ivan R.] Univ British Columbia, Dept Cellular & Physiol Sci, Vancouver, BC V5Z 1M9, Canada. [Wang, Yu Tian] Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada. [Wang, Yu Tian] Brain Res Ctr, Vancouver, BC, Canada. [Luo, Honglin] Univ British Columbia, Dept Pathol & Lab Med, James Hogg Res Ctr, Vancouver, BC V5Z 1M9, Canada. [Shi, Junyan] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. [Toker, Lilach] Univ British Columbia, Dept Psychiat, Vancouver, BC V5Z 1M9, Canada. [Gleave, Martin] Univ British Columbia, Dept Urol Sci, Vancouver, BC V5Z 1M9, Canada. [Jiang, Xiaoyan] Univ British Columbia, Med Genet & BC Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1M9, Canada. [Piret, James M.] Univ British Columbia, Michael Smith Labs, Dept Chem & Biol Engn, Vancouver, BC V5Z 1M9, Canada. [Turner, Robin F. B.] Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, Canada. [Blanco, Guillermo A.] Univ Buenos Aires, IDEHU CONICET, Fac Pharm & Biochem, Buenos Aires, DF, Argentina. [Alvarez, Silvia] Univ Buenos Aires, Inst Biochem & Biophys, Sch Pharm & Biochem, Buenos Aires, DF, Argentina. [Vaccaro, Maria I.] Univ Buenos Aires, Natl Council Sci & Tech Res CONICET, Inst Biochem & Mol Med, Dept Pathophysiol,Sch Pharm & Biochem, Buenos Aires, DF, Argentina. [Perrotta, Ida] Univ Calabria, Dept Biol Ecol & Earth Sci, Lab Electron Microscopy, I-87036 Cosenza, Italy. [Aquila, Saveria] Univ Calabria, Dept Pharm Hlth & Nutrit Sci, I-87036 Cosenza, Italy. [Russo, Rossella] Univ Calabria, Dept Pharm Hlth & Nutrit Sci, Sect Preclin & Translat Pharmacol, I-87036 Cosenza, Italy. [Chakrabarti, Gopal] Univ Calcutta, Dept Biotechnol, Dr BC Guha Ctr Genet Engn & Biotechnol, Kolkata, WB, India. [Zheng, Xi-Long] Univ Calgary, Dept Biochem & Mol Biol, Libin Cardiovasc Inst Alberta, Calgary, AB, Canada. [Schatzl, Hermann M.] Univ Calgary, Fac Vet Med, Calgary, AB, Canada. [Hurley, James H.; Thorner, Jeremy] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Ge, Liang; Schekman, Randy] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Kung, Hsing-Jien] Univ Calif Davis, Ctr Canc, Davis, CA 95616 USA. [Luckhart, Shirley; Pakpour, Nazzy] Univ Calif Davis, Dept Med Microbiol & Immunol, Sch Med, Davis, CA 95616 USA. [Powers, Ted] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA. [Gomes, Aldrin V.] Univ Calif Davis, Dept Neurobiol Physiol & Behav, Davis, CA 95616 USA. [Dinesh-Kumar, Savithrama P.] Univ Calif Davis, Dept Plant Biol, Davis, CA 95616 USA. [Dinesh-Kumar, Savithrama P.] Coll Biol Sci, Genome Ctr, Davis, CA USA. [van Doorn, Wouter G.] Univ Calif Davis, Mann Lab, Dept Plant Sci, Davis, CA 95616 USA. [Edinger, Aimee L.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA. [Chen, Jeff W.] Univ Calif Irvine, Dept Neurosurg, Irvine, CA USA. [Steffan, Joan] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Ganesan, Anand K.] Univ Calif Irvine, Irvine, CA USA. [Xia, Tian] Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA. [Costes, Safia] Univ Calif Los Angeles, David Geffen Sch Med, Larry Hillblom Islet Res Ctr, Los Angeles, CA 90095 USA. [Le Roch, Karine G.] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. [Steele, John W.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Lee, Jongdae; Satriano, Joseph] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Sigurdson, Christina J.] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. [Spector, Stephen A.] Univ Calif San Diego, Dept Pediat Div Infect Dis, La Jolla, CA 92093 USA. [Campbell, Grant R.; Ordonez, Paulina] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. [Guan, Kun-Liang] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. [Guan, Kun-Liang] Moores Canc Ctr, La Jolla, CA USA. [Miyamoto, Shigeki] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. [La Spada, Albert R.] Univ Calif San Diego, Dept Cellular & Mol Med, Div Biol Sci, Inst Genom Med, La Jolla, CA 92093 USA. [La Spada, Albert R.] Univ Calif San Diego, Dept Neurosci, Div Biol Sci, Inst Genom Med, La Jolla, CA 92093 USA. [La Spada, Albert R.] Univ Calif San Diego, Dept Pediat, Div Biol Sci, Inst Genom Med, La Jolla, CA 92093 USA. [Kiger, Amy A.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. [Liu, Jing-Jing; Nazarko, Taras Y.] Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA. [Till, Andreas] Univ Calif San Diego, San Diego Ctr Syst Biol, La Jolla, CA 92093 USA. [Cohen, Ezra E. W.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Soontornniyomkij, Virawudh] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. [Gustafsson, Asa B.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Cox, Jeffery S.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. [Aghi, Manish K.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [An, Zhenyi] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Hetz, Claudio; Matus, Soledad] FONDAP Ctr Gerosci Brain Hlth & Metab, Santiago, Chile. [Gestwicki, Jason E.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. [Sarwal, Minnie M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Finkbeiner, Steven] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Finkbeiner, Steven] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. [Finkbeiner, Steven] Gladstone Inst Neurol Dis, San Francisco, CA USA. [Debnath, Jayanta; Margeta, Marta] Univ Calif San Francisco, Sch Med, Dept Pathol, San Francisco, CA 94143 USA. [Kajimura, Shingo] Univ Calif San Francisco, UCSF Diabet Ctr, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA. [Montell, Craig] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA. [Kaser, Arthur] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England. [Rubinsztein, David C.] Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, Dept Med Genet, Cambridge CB2 2QQ, England. [Floto, R. Andres] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England. [Narita, Masashi] Univ Cambridge, Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Cambridge, England. [Miller-Fleming, Leonor] Univ Cambridge, Dept Biochem, Cambridge, England. [Renna, Maurizio] Univ Cambridge, Dept Med Genet, Cambridge Inst Med Res, Cambridge, England. [Randow, Felix] Univ Cambridge, Dept Med, Addenbrookes Hosp, Cambridge CB2 2QQ, England. [Beale, Rupert] Univ Cambridge, Dept Pathol, Div Virol, Tennis Court Rd, Cambridge CB2 1QP, England. [Amantini, Consuelo] Univ Camerino, Sch Biosci & Vet Med, I-62032 Camerino, Italy. [Nabissi, Massimo] Univ Camerino, Sch Pharm, I-62032 Camerino, Italy. [Santoni, Giorgio] Univ Camerino, Sch Pharm, Sect Expt Med, I-62032 Camerino, MC, Italy. [Ferreira-Halder, Carmen Verissima] Univ Estadual Campinas, Dept Biochem & Tissue Biol, Campinas, SP, Brazil. [Dobson, Renwick C. J.] Univ Canterbury, Biomol Interact Ctr, Sch Biol Sci, Christchurch 1, New Zealand. [Prince, Sharon] Univ Cape Town, Dept Human Biol, ZA-7925 Cape Town, Western Provinc, South Africa. [Davids, Lester M.] Univ Cape Town, Redox Lab, Dept Human Biol, ZA-7925 Cape Town, South Africa. [Zervos, Antonis S.] Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32816 USA. [He, Yu-Ying] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA. [Choi, Jayoung; Hwang, Seungmin] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Mastrianni, James A.] Univ Chicago, Pritzker Sch Med, Dept Neurol, Chicago, IL 60637 USA. [Macleod, Kay F.] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA. [Corbalan, Ramon; Garcia Nannig, Lorena] Univ Chile, Adv Ctr Chron Dis ACCDiS, Div Cardiovasc Dis, Fac Med, Santiago, Chile. [Pedrozo, Zully] P Catholic Univ Chile, Adv Ctr Chron Dis ACCDiS, Fac Med, Santiago, Chile. [Matus, Soledad] Univ Chile, Biomed Neurosci Inst, Santiago, Chile. [Segura-Aguilar, Juan] Univ Chile, Fac Med, ICBM Mol & Clin Pharmacol, Santiago 7, Chile. [Hetz, Claudio] Univ Chile, Fac Med, Inst Biomed Sci, Ctr Mol Studies Cell,Program Cellular,Mol Biol &, Santiago 7, Chile. [Weaver, Timothy E.] Univ Cincinnati, Coll Med, Cincinnati Childrens Res Fdn, Cincinnati, OH USA. [Weaver, Timothy E.] Dept Pediat, Cincinnati, OH USA. [Czyzyk-Krzeska, Maria F.; Guan, Jun-Lin; Wang, Chenran] Dept Pediat, Coll Med, Dept Canc Biol, Cincinnati, OH USA. [Robbins, Jeffrey] Univ Cincinnati, Cincinnati Childrens Hosp, Cincinnati, OH USA. [Choubey, Divaker] Univ Cincinnati, Cincinnati, OH USA. [Moreira, Paula I.] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Moreira, Paula I.] Fac Med, Coimbra, Portugal. [Cruz, Maria Teresa; Liberal, Joana] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Cruz, Maria Teresa; Liberal, Joana] Fac Pharm, Coimbra, Portugal. [Vega-Naredo, Ignacio] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Cantanhede, Portugal. [Batista, Maria Teresa] Univ Coimbra, Coimbra, Portugal. [Cardoso, Sandra Morais] Univ Coimbra, Fac Med, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Pereira, Paulo C.] Univ Coimbra, IBILI, Fac Med, Coimbra, Portugal. [Fabri, Mario] Univ Cologne, Dept Dermatol, D-50931 Cologne, Germany. [Hoppe, Thorsten] Univ Cologne, Inst Genet, CECAD Res Ctr, D-50931 Cologne, Germany. [Noegel, Angelika A.] Univ Cologne, Inst Biochem 1, Fac Med, Cologne, Germany. [Eichinger, Ludwig] Univ Cologne, Fac Med, Ctr Biochem, D-50931 Cologne, Germany. [Edelstein, Charles L.] Univ Colorado, Boulder, CO 80309 USA. [Weekes, Colin D.] Univ Colorado, Div Med Oncol, Dept Med, Aurora, CO USA. [Agarwal, Rajesh; Raina, Komal] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Aurora, CO USA. [Jani, Alkesh] Univ Colorado, Denver, CO USA. [Jani, Alkesh] Denver VAMC, Denver, CO USA. [Levy, Jean M. Mulcahy] Univ Colorado, Dept Pediat, Ctr Canc & Blood Disorders, Aurora, CO USA. [Parker, Roy] Univ Colorado, HHMI, Dept Chem & Biochem, Aurora, CO USA. [Pugazhenthi, Subbiah] Univ Colorado, Sch Med, Anschutz Med Campus, Aurora, CO USA. [Reusch, Jane E. B.] Univ Colorado, Sch Med, Aurora, CO USA. [Pyeon, Dohun] Univ Colorado, Sch Med, Dept Immunol & Microbiol, Aurora, CO USA. [Bayer, K. Ulrich; Morgan, Michael J.; Thorburn, Andrew] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO USA. [Beckham, J. David] Univ Colorado, Sch Med, Div Infect Dis, Aurora, CO USA. [Frankel, Lisa B.; Issazadeh-Navikas, Shohreh; Lund, Anders H.] Univ Copenhagen, BRIC, Copenhagen, Denmark. [Petersen, Morten] Univ Copenhagen, Dept Biol, Copenhagen, Denmark. [Olsson, Stefan] Univ Copenhagen, Dept Plant & Environm Sci, Sect Genet & Microbiol, Copenhagen, Denmark. [Tavernarakis, Nektarios] Univ Crete, Dept Basic Sci, Fac Med, Iraklion, Greece. [Tavernarakis, Nektarios] Univ Crete, Inst Mol Biol & Biotechnol, Iraklion, Greece. [Chamilos, Georgios; Kyrmizi, Irene] Univ Crete, Sch Med, Dept Infect Dis, Iraklion, Greece. [Promponas, Vasilis J.] Univ Cyprus, Dept Biol Sci, Bioinformat Res Lab, CY-1678 Nicosia, Cyprus. [Fesus, Laszlo] Univ Debrecen, Debrecen, Hungary. [Lekli, Istvan] Univ Debrecen, Fac Pharm, Dept Pharmacol, Debrecen, Hungary. [van Golen, Kenneth L.] Univ Delaware, Dept Biol Sci, Newark, DE USA. [van Golen, Kenneth L.] Univ Delaware, Ctr Translat Canc Res, Newark, DE USA. [Rocha, Sonia] Univ Dundee, Ctr Gene Regulat & Express, Coll Life Sci, Dundee DD1 4HN, Scotland. [Ganley, Ian G.] Univ Dundee, MRC Prot Phosphorylat & Ubiquitylat Unit, Sch Life Sci, Dundee, Scotland. [Wileman, Tom] Univ E Anglia, Norwich Med Sch, Norwich NR4 7TJ, Norfolk, England. [Pesonen, Maija] Univ Eastern Finland, Fac Hlth Sci, Sch Pharm Toxicol, Kuopio, Finland. [Kaarniranta, Kai] Univ Eastern Finland, Kuopio Univ Hosp, Dept Ophthalmol, Kuopio, Finland. [Digard, Paul] Univ Edinburgh, Easter Bush, Roslin Insitute, Edinburgh EH8 9YL, Midlothian, Scotland. [Gammoh, Noor] Univ Edinburgh, Edinburgh Canc Res Ctr, Edinburgh, Midlothian, Scotland. [Wilkinson, Simon] Univ Edinburgh, Edinburgh Canc Res UK Ctr, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Distler, Joerg H. W.] Univ Erlangen Nurnberg, Dept Internal Med 3, D-91054 Erlangen, Germany. [Moore, Michael N.] Univ Exeter, Sch Med, ECEHH, Truro, Cornwall, England. [Talbot, Nicholas J.] Univ Exeter, Sch Biosci, Exeter, Devon, England. [Pena, Fernando J.; Tapia, Jose A.] Univ Extremadura, Dept Med, Fac Vet Med, Caceres, Spain. [Neri, Luca M.; Pinton, Paolo] Univ Ferrara, Dept Morphol Surg & Expt Med, I-44100 Ferrara, Italy. [Papini, Alessio] Univ Florence, Dept Biol, Florence, Italy. [Dunn, William A., Jr.] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL USA. [Notterpek, Lucia] Univ Florida, Coll Med, Dept Neurosci, Gainesville, FL USA. [Joseph, Anna-Maria] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. [Wohlgemuth, Stephanie E.] Univ Florida, Dept Anim Sci, IFAS Coll Agr & Life Sci, Gainesville, FL 32611 USA. [Adhihetty, Peter J.; Powers, Scott K.] Univ Florida, Dept Appl Physiol & Kinesiol, Gainesville, FL USA. [Maegawa, Gustavo] Univ Florida, Dept Pediat Genet & Metab, Gainesville, FL USA. [Behrns, Kevin E.] Univ Florida, Dept Surg, Gainesville, FL USA. [Kim, Jae-Sung] Univ Florida, Gainesville, FL USA. [Leeuwenburgh, Christiaan] Univ Florida, Inst Aging, Gainesville, FL USA. [Dengjel, Joern] Univ Freiburg, Dept Dermatol, Med Ctr, Ctr Biol Syst Anal ZBSA, Hugstetter Str 55, D-79106 Freiburg, Germany. [Yang, Zhihong] Univ Fribourg, Dept Med, Div Physiol, Fac Sci, CH-1700 Fribourg, Switzerland. [Ming, Xiu-Fen; Xiong, Yuyan] Univ Fribourg, Dept Med, Div Physiol, CH-1700 Fribourg, Switzerland. [Gannage, Monique] Univ Geneva, Sch Med, Dept Pathol & Immunol, CH-1211 Geneva, Switzerland. [Gogal, Robert M., Jr.] Univ Georgia, Coll Vet Med, Dept Biosci & Diagnost Imaging, Athens, GA 30602 USA. [Quinn, Frederick] Univ Georgia, Dept Infectious Dis, Athens, GA 30602 USA. [Leung, Hing Y.; Ryan, Kevin M.; Tait, Stephen W. G.] Univ Glasgow, Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland. [Leung, Hing Y.; McNeish, Iain A.] Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland. [Evans, Thomas J.] Univ Glasgow, Inst Infect Immun & Inflammat, Glasgow, Lanark, Scotland. [Helgason, Gudmundur Vignir] Univ Glasgow, Wolfson Wohl Canc Res Ctr, MVLS, Inst Canc Sci, Glasgow, Lanark, Scotland. [Jackson, Daniel John] Univ Gottingen, Dept Geobiol, D-37073 Gottingen, Germany. [Lingor, Paul] Univ Gottingen, Dept Neurol, D-37073 Gottingen, Germany. [Carmona-Gutierrez, Didac; Eisenberg, Tobias; Kohlwein, Sepp D.; Madeo, Frank] Graz Univ, Inst Mol Biosci, BioTechMed Graz, Graz, Austria. [van der Klei, Ida J.; Williams, Chris] Univ Groningen, Mol Cell Biol, Groningen, Netherlands. [Lemberg, Marius K.] Heidelberg Univ, Ctr Mol Biol, Heidelberg, Germany. [Parlato, Rosanna] Heidelberg Univ, Inst Anat & Cell Biol, Heidelberg, Germany. [Lindholm, Dan] Univ Helsinki, Biomedicum, Helsinki, Finland. [Eskelinen, Eeva-Liisa; Stratoulias, Vassilis] Univ Helsinki, Dept Biosci, Helsinki, Finland. [Hulmi, Juha J.] Univ Helsinki, Dept Physiol, Fac Med, Helsinki, Finland. [Wang, Yu] Univ Hong Kong, Dept Pharmacol & Pharm, Hong Kong, Hong Kong, Peoples R China. [Su, Yu-Xiong] Univ Hong Kong, Div Oral & Maxillofacial Surg, Fac Dent, Hong Hom, Hong Kong, Peoples R China. [Feng, Yibin] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Chang, Raymond Chuen-Chung] Univ Hong Kong, Lab Neurodegenerat Dis, Sch Biomed Sci, LKS Fac Med, Hong Kong, Hong Kong, Peoples R China. [Eriksen, Jason L.; Zhang, Yang] Univ Houston, Coll Pharm Pharmacol & Pharmaceut Sci, Houston, TX USA. [Frigo, Daniel E.] Univ Houston, Dept Biol & Biochem, Ctr Nucl Receptors & Cell Signaling, Houston, TX USA. [Caplan, Allan B.] Univ Idaho, Plant Soil & Entomol Sci, Moscow, ID USA. [Yue, Beatrice Y. J. T.] Univ Illinois, Coll Med, Dept Ophthalmol & Visual Sci, Chicago, IL USA. [Zhou, Guofei] Univ Illinois, Coll Med, Dept Pediat, Chicago, IL USA. [Hu, Guochang] Univ Illinois, Dept Anesthesiol, Chicago, IL USA. [Hu, Guochang] Univ Illinois, Dept Pharmacol, Chicago, IL USA. [Shukla, Deepak] Univ Illinois, Dept Ophthalmol, Chicago, IL 60680 USA. [Shukla, Deepak] Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60680 USA. [Nazarko, Volodymyr Y.; Segev, Nava] Univ Illinois, Deprtment Biochem & Mol Genet, Chicago, IL USA. [Sun, Jun] Univ Illinois, Div Gastroenterol & Hepatol, Dept Med, Chicago, IL USA. [Kemper, Jongsook Kim] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL USA. [Zhang, Guo-Chang] Univ Illinois, Inst Genom Biol, Urbana, IL USA. [Meryk, Andreas] Univ Innsbruck, Inst Biomed Aging Res, A-6020 Innsbruck, Austria. [Romanelli, Davide; Tettamanti, Gianluca] Univ Insubria, Dept Biotechnol & Life Sci, Varese, Italy. [Grose, Charles] Univ Iowa, Childrens Hosp, Iowa City, IA USA. [Lira, Vitor A.] Univ Iowa, Dept Hlth & Human Physiol, Iowa City, IA USA. [Adams, Christopher M.] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. [Monick, Martha M.] Univ Iowa, Dept Med, Iowa City, IA 52242 USA. [Fingert, John H.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA. [Hulmi, Juha J.] Univ Jyvaskyla, Dept Biol Phys Act, SF-40100 Jyvaskyla, Finland. [Marquez, Rebecca; Xu, Liang] Univ Kansas, Lawrence, KS 66045 USA. [Marquez, Rebecca; Xu, Liang] Univ Kansas, Ctr Canc, Dept Mol Biosci, Lawrence, KS 66045 USA. [Marquez, Rebecca; Xu, Liang] Univ Kansas, Ctr Canc, Dept Radiat Oncol, Lawrence, KS 66045 USA. [Chen, Qi; Ding, Wen-Xing] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. [Hsu, Chin] Univ Kaohsiung, Med Univ, Dept Physiol, Fac Med,Coll Med, Kaohsiung, Taiwan. [Chen, Gang; Luo, Jia] Univ Kentucky, Coll Med, Dept Pharmacol & Nutrit Sci, Lexington, KY USA. [Rucker, Edmund B., III] Univ Kentucky, Dept Biol, Lexington, KY USA. [Dickson, Robert C.] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY USA. [Craven, Rolf J.] Univ Kentucky, Dept Pharmacol & Nutrit Sci, Lexington, KY USA. [St Clair, Daret] Univ Kentucky, Dept Toxicol & Canc Biol, Lexington, KY USA. [Frey, Norbert; Kuhn, Christian] Univ Kiel, Dept Cardiol, Kiel, Germany. [Rosenstiel, Philip] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Huebbe, Patricia; Pallauf, Kathrin; Rimbach, Gerald] Univ Kiel, Inst Human Nutr & Food Sci, Kiel, Germany. [Denizot, Melanie] Univ La Reunion, CYROI, IRG Immunopathol & Infect Res Grouping, Reunion, Reunion. [Gravina, Giovanni Luca] Univ Aquila, Dept Biotechnol & Appl Clin Sci, Div Radiotherapy & Radiobiol, I-67100 Laquila, Italy. [Mayer, Andreas] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Clarke, Peter G. H.; Ginet, Vanessa; Puyal, Julien] Univ Lausanne, Dept Fundamental Neurosci, Fac Biol & Med, Lausanne, Switzerland. [Cottet, Sandra; Schorderet, Daniel F.] Univ Lausanne, Dept Ophthalmol, Lausanne, Switzerland. [Noureini, Sakineh Kazemi] Hakim Sabzevari Univ, Dept Biol, Fac Basic Sci, Sabzevar, Iran. [Andreadi, Catherine K.; Brown, Karen] Univ Leicester, Dept Canc Studies, Leicester, Leics, England. [Giorgini, Flaviano] Univ Leicester, Dept Genet, Leicester, Leics, England. [Garg, Abhishek D.] Univ Leuven, Campus Gasthuisberg, Dept Cellular & Mol Med, Lab Cell Death Res & Therapy, Leuven, Belgium. [Vandenberghe, Wim] Univ Leuven, Dept Neurosci, Leuven, Belgium. [Claerhout, Sofie] KU Leuven Univ Leuven, Ctr Human Genet, Leuven, Belgium. [Claerhout, Sofie] VIB Ctr Biol Dis, Leuven, Belgium. [Mottet, Denis] Univ Liege, GIGA Signal Transduct Dept, Prot Signalisat & Interact Lab, Liege, Belgium. [Staels, Bart] Univ Lille, INSERM UMR1011, Inst Pasteur Lille, Lille, France. [Terro, Faraj] Univ Limoges, Dept Histol & Cell Biol, Limoges, France. [Clague, Michael J.] Univ Liverpool, Cellular & Mol Physiol, Inst Translat Med, Liverpool L69 3BX, Merseyside, England. [Erman, Andreja] Univ Ljubljana, Inst Cell Biol, Fac Med, Ljubljana, Slovenia. [Campanella, Michelangelo] Univ London, RVC Dept Comparat Biomed Sci, UCL Consortium Mitochondrial Res, London, England. [Sylvester, Paul W.] Univ Louisiana Monroe, Sch Pharm, Monroe, LA USA. [Cheng, Alan] Univ Louisville, Dept Biochem & Mol Genet, Louisville, KY 40292 USA. [Chesney, Jason; Telang, Sucheta] Univ Louisville, Dept Med Hem Onc, Louisville, KY 40292 USA. [Hill, Bradford G.] Univ Louisville, Dept Med, Inst Mol Cardiol, Diabet & Obes Ctr, Louisville, KY 40292 USA. [Sen, Utpal] Univ Louisville, Dept Physiol, Louisville, KY 40292 USA. [Li, Chi] Univ Louisville, James Graham Brown Canc Ctr, Dept Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. [Kumar, Ashok] Univ Louisville, Sch Med, Dept Anat Sci & Neurobiol, Louisville, KY 40292 USA. [Tyagi, Suresh C.] Univ Louisville, Sch Med, Dept Physiol & Biophys, Louisville, KY 40292 USA. [Kruger, Rejko] Univ Luxembourg, Luxembourg Ctr Syst Biomed, Luxembourg, Luxembourg. [Lu, Jiahong] Univ Macau, State Key Lab Qual Res Chinese Med, Inst Chinese Med Sci, Macau, Peoples R China. [Balzan, Rena] Univ Malta, Dept Physiol & Biochem, Fac Med & Surg, Msida, Malta. [Lisanti, Michael P.] Univ Manchester, Breakthrough Breast Canc Res Unit, Manchester Ctr Cellular Metab, Manchester M13 9PL, Lancs, England. [Tournier, Cathy] Univ Manchester, Fac Life Sci, Manchester, Lancs, England. [Sotgia, Federica] Univ Manchester, Inst Canc Sci, Fac Med & Human Sci, Manchester, Lancs, England. [Gibson, Spencer B.] Univ Manitoba, CancerCare Manitoba, Manitoba Inst Cell Biol, Dept Biochem, Winnipeg, MB, Canada. [Gibson, Spencer B.] Univ Manitoba, Dept Med Genet & Immunol, Winnipeg, MB, Canada. [Ghavami, Saeid] Univ Manitoba, Dept Human Anat & Cell Sci, Winnipeg, MB, Canada. [Halayko, Andrew J.] Univ Manitoba, Dept Physiol & Pathophysiol, Winnipeg, MB, Canada. [Kirshenbaum, Lorrie A.] Univ Manitoba, Inst Cardiovasc Sci, Coll Med, Fac Hlth Sci, Winnipeg, MB, Canada. [Sharma, Shweta] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Zhang, Yanjin] Univ Maryland, Dept Vet Med, College Pk, MD 20742 USA. [Fang, Shengyun] Univ Maryland, Sch Med, Sch Med, Ctr Biomed Engn & Technol,Dept Physiol, Baltimore, MD 21201 USA. [Wu, Junfang] Univ Maryland, Sch Med, Dept Anesthesiol & Ctr Shock, Trauma & Anesthesiol Res STAR,Natl Study Ctr Trau, Baltimore, MD 21201 USA. [Lipinski, Marta M.] Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. [Njar, Vincent C. O.] Univ Maryland, Sch Med, Dept Chem, Baltimore, MD 21201 USA. [Jackson, William T.; Kalvakolanu, Dhan V.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Yang, Peixin] Univ Maryland, Sch Med, Dept Obstet Gynecol & Reprod Sci, Baltimore, MD 21201 USA. [Aurelian, Laure] Univ Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21201 USA. [Cheng, Hua] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Baehrecke, Eric H.; Velentzas, Panagiotis D.] Univ Massachusetts, Sch Med, Dept Mol Cell & Canc Biol, Worcester, MA 01605 USA. [Gao, Fen-Biao] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA. [Davis, Roger J.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA. [Maiese, Kenneth] Univ Med & Dent New Jersey, Cellular & Mol Signaling, Newark, NJ 07103 USA. [Lindqvist, Lisa M.] Cell Signalling & Cell Death Div, Parkville, Vic, Australia. [Lindqvist, Lisa M.] Univ Melbourne, Walter & Eliza Hall Inst Med Res, Dept Med Biol, Parkville, Vic 3052, Australia. [White, Anthony R.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. [Delbridge, Lea M. D.] Univ Melbourne, Dept Physiol, Parkville, Vic 3052, Australia. [Pepe, Salvatore] Univ Melbourne, Murdoch Childrens Res Inst, Dept Paediat, Royal Childrens Hosp, Melbourne, Vic, Australia. [Kim, Michael D.] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA. [Man, Na] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Soleimanpour, Scott A.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Lieberman, Andrew P.; Lukacs, Nicholas W.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. [Towns, Roberto] Univ Michigan, Ann Arbor, MI 48109 USA. [Duncan, Mara C.] Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. [Swanson, Michele S.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Lee, Jun Hee] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Klionsky, Daniel J.; Feng, Yuchen; Gatica, Damian; Jin, Meiyan; Kumar, Anuj; Liu, Xu; Orban, Daniel P.; Parzych, Katherine R.; Wen, Xin; Xu, Haoxing; Xu, Ziheng; Yao, Zhiyuan] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. [Zacks, David N.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Xie, Chuan-Ming] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Sun, Yi; Zhao, Yongchao] Univ Michigan, Dept Radiat Oncol, Div Radiat & Canc Biol, Ann Arbor, MI 48109 USA. [Klionsky, Daniel J.; Ariosa, Aileen R.; Bernard, Amelie; Delorme-Axford, Elizabeth; Feng, Yuchen; Gatica, Damian; Jin, Meiyan; Liu, Xu; Orban, Daniel P.; Parzych, Katherine R.; Popelka, Hana; Wen, Xin; Xu, Ziheng; Yao, Zhiyuan] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Burmeister, Margit] Univ Michigan, Mol & Behav Neurosci Inst, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Burmeister, Margit] Univ Michigan, Mol & Behav Neurosci Inst, Dept Psychiat, Ann Arbor, MI 48109 USA. [Burmeister, Margit] Univ Michigan, Mol & Behav Neurosci Inst, Dept Human Genet, Ann Arbor, MI 48109 USA. [Hua, Ya] Univ Michigan, Neurosurg, Ann Arbor, MI 48109 USA. [Kahana, Alon] Univ Michigan, Ophthalmol & Visual Sci, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. [Liu, Fei] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. [Minucci, Saverio] Univ Milan, Dept Expt Oncol, European Inst Oncol, Milan, Italy. [Minucci, Saverio] Dept Biosci, Milan, Italy. [Avagliano, Laura; Marconi, Anna Maria] Univ Milan, Dept Hlth Sci, Milan, Italy. [Vitale, Giovanni] Univ Milan, Ist Auxol Italiano, Dept Clin Sci & Community Hlth, Milan, Italy. [Ludovico, Paula] Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Hlth Sci, Braga, Portugal. [Sousa, Maria Joao] Univ Minho, Mol & Environm Biol Ctr CBMA, Dept Biol, Braga, Portugal. [Ludovico, Paula] ICVS 3Bs PT Govt Associate Lab, Braga, Portugal. [Kim, Do-Hyung] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN USA. [Mauvezin, Caroline] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA. [Abedin, Md Joynal] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Karim, Md Razaul] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA. [Saluja, Ashok K.] Univ Minnesota, Dept Surg, Box 242 UMHC, Minneapolis, MN 55455 USA. [Imbriano, Carol; Pinti, Marcello] Univ Modena & Reggio Emilia, Dept Life Sci, Modena, Italy. [Gibellini, Lara] Univ Modena & Reggio Emilia, Dept Surg Med Dent & Morphol Sci, Modena, Italy. [Cossarizza, Andrea] Univ Modena & Reggio Emilia, Sch Med, Dept Surg Med Dent & Morphol Sci, Modena, Italy. [Koechlin-Ramonatxo, Christelle] Univ Montpellier, INRA, UMR 866, Dynam Musculaire & Metab, F-34059 Montpellier, France. 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[Auberger, Patrick] Univ Nice, INSERM U1065, C3M, Nice, France. [Hofman, Paul] Univ Nice Sophia Antipolis, INSERM U1081, CNRS 7284, Fac Med, F-06189 Nice, France. [Bulavin, Dmitry V.] Univ Nice Sophia Antipolis, IRCAN, F-06189 Nice, France. [Vouret-Craviari, Valerie] Univ Nice Sophia Antipolis, IRCAN, F-06189 Nice, France. [Aoki, Hiroshi] Niigata Univ, Dept Neurosurg, Brain Res Inst, Niigata, Japan. [Bultman, Scott J.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Ting, Jenny Pan-yun] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. [Der, Channing J.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Ting, Jenny Pan-yun] Univ N Carolina, Lineberger Comprehens Canc Ctr, Inst Inflammatory Dis, Ctr Translat Immunol, Chapel Hill, NC 27599 USA. [Kawula, Thomas] Univ N Carolina, Microbiol & Immunol, Chapel Hill, NC USA. [Wu, Min] Univ N Dakota, Dept Biomed Sci, Sch Med & Hlth Sci, Grand Forks, ND 58201 USA. [Basu, Alakananda] Univ N Texas, Hlth Sci Ctr, Dept Mol & Med Genet, Ft Worth, TX USA. [Layfield, Robert] Univ Nottingham, Sch Life Sci, Nottingham NG7 2RD, England. [Adachi, Hiroaki] Univ Occupat & Environm Hlth, Sch Med, Dept Neurol, Fukuoka, Japan. [Harada, Masaru] Univ Occupat & Environm Hlth, Dept Internal Med 3, Kitakyushu, Fukuoka, Japan. [Xu, Jian] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Ramesh, Rajagopal; Zhao, Zhizhuang J.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. [Xie, Zhonglin] Univ Oklahoma, Hlth Sci Ctr, Sect Mol Med, Dept Med, Oklahoma City, OK USA. [Jain, Ashish; Rusten, Tor Erik] Univ Oslo, Ctr Canc Biomed, Oslo, Norway. [Seglen, Per O.] Univ Oslo, Ctr Mol Med Norway NCMM, Oslo, Norway. [Torgersen, Maria Lyngaas] Univ Oslo, Dept Biochem, Inst Canc Res, Oslo, Norway. [Mills, Ian G.] Univ Oslo, Dept Mol Oncol, Dept Urol, Oslo, Norway. [Nilsen, Hilde] Univ Oslo, Dept Clin Mol Biol, Oslo, Norway. [Petrovski, Goran] Univ Oslo, Dept Ophthalmol, Oslo, Norway. [Mills, Ian G.] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Lisburn Rd, Belfast, Antrim, North Ireland. [Blomhoff, Heidi Kiil; Simonsen, Anne] Univ Oslo, Inst Basic Med Sci, Oslo, Norway. [Engedal, Nikolai; Gerner, Lisa] Univ Oslo, Oslo Univ Hosp, Ctr Mol Med Norway, Nord EMBL Partnership, Oslo, Norway. [Hensel, Michael] Univ Osnabrueck, Div Microbiol, Osnabruck, Germany. [Ungermann, Christian] Univ Osnabrueck, Fachbereich Biol Chem, Osnabruck, Germany. [Slack, Ruth] Univ Ottawa, Dept Cellular & Mol Med, Fac Med, Ottawa, ON, Canada. [Gibbings, Derrick J.] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada. [Marino, Guillermo] Univ Oviedo, Dept Anim Physiol, Fac Med, Campus Cristo, Oviedo, Spain. [Buchan, Alastair M.] Univ Oxford, Acute Stroke Programme, Radcliffe Dept Med, Oxford, England. [Hammond, Ester M.] Univ Oxford, CRUK MRC Oxford Inst Radiat Oncol, Oxford, England. [Poulton, Joanna] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford, England. [Brini, Marisa; Valle, Luisa Dalla; Scovassi, A. Ivana] Univ Padua, Dept Biol, Padua, Italy. [Bonaldo, Paolo; Chen, Peiwen; Grumati, Paolo] Univ Padua, Dept Mol Med, Padua, Italy. [Viola, Giampietro] Univ Padua, Dept Womans & Childs Hlth, Lab Oncohematol, Padua, Italy. [Monick, Martha M.; Sandri, Marco; Zaglia, Tania] Univ Padua, Venetian Inst Mol Med, Dept Biomed Sci, Padua, Italy. [Agnello, Maria; Chiarelli, Roberto; Luparello, Claudio; Roccheri, Maria Carmela] Univ Palermo, Dipartimento Sci &Tecnol Biol, Chim & Farmaceutiche STEBICEF, Palermo, Italy. [Bettuzzi, Saverio; Rizzi, Federica] Univ Parma, Dept Biomed Biotechnol & Translat Sci, I-43100 Parma, Italy. [Comincini, Sergio; Palumbo, Silvia] Univ Pavia, Dept Biol & Biotechnol, Via Palestro 3, I-27100 Pavia, Italy. [Emanuele, Enzo] Univ Pavia, Dept Hlth Sci, Via Palestro 3, I-27100 Pavia, Italy. [Koumenis, Constantinos] Univ Penn, Perelman Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [O'Dwyer, Peter J.; Vogl, Dan T.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Gonzalez-Alegre, Pedro] Univ Penn, Ctr Cell & Mol Therapy, Children Hosp Philadelphia, Dept Neurol,Perelman Sch Med, Philadelphia, PA 19104 USA. [Mitchell, Claire H.] Univ Penn, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. [Boesze-Battaglia, Kathleen] Univ Penn, Dept Biochem, SDM, Philadelphia, PA 19104 USA. [Cherry, Sara] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. [Zhang, Lin] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Zhang, Lin] Perelman Sch Med, Philadelphia, PA USA. [Sanchez, Anthony M. J.] Univ Perpignan Via Domitia, Lab Europee Performance St Altitude, EA 4604, Ft Romeu, France. [Romani, Luigina] Univ Perugia, Dept Expt Med, I-06100 Perugia, Italy. [De Tata, Vincenzo; Fornai, Francesco; Lenzi, Paola] Univ Pisa, Dept Translat Res & New Technol Med & Surg, Pisa, Italy. [Cavallini, Gabriella] Univ Pisa, Interdepartmental Res Ctr Biol & Pathol Aging, Pisa, Italy. [Singh, Shivendra V.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr Res Pavil, Pittsburgh, PA USA. [Johnson, Daniel E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Tsung, Allan] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA USA. [Gomez, Hernando] Univ Pittsburgh, Dept Crit Care Med, Ctr Crit Care Nephrol, Clin Res Invest & Syst Modeling Acute Illness, Pittsburgh, PA USA. [Coyne, Carolyn B.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA USA. [Rabinowich, Hannah] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Kang, Rui; Tang, Daolin] Univ Pittsburgh, Dept Surg, Hillman Canc Ctr, Pittsburgh, PA USA. [Fan, Jie; Lee, Yong J.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Lotze, Michael T.] Univ Pittsburgh, Dept Surg, Inst Canc, Pittsburgh, PA USA. [Perlmutter, David H.] Univ Pittsburgh, Pittsburgh, PA USA. [Ouyang, Hongjiao] Univ Pittsburgh, Sch Dent Med, Dept Endodont, Pittsburgh, PA USA. [Kaynar, A. Murat] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA USA. [Kaynar, A. Murat] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA USA. [Lu, Binfeng] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA USA. [Chu, Charleen T.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Chu, Charleen T.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA. [Pak, Stephen C.; Silverman, Gary A.] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15260 USA. [Zhang, Lin] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15260 USA. [Stang, Michael T.] Univ Pittsburgh, Sch Med, Dept Surg, Div Endocrine Surg, Pittsburgh, PA 15260 USA. [Isenberg, Jeffrey S.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15260 USA. [Page, Guylene] Univ Poitiers, Mol Targets & Therapeut Alzheimers Dis EA3808, Poitiers, France. [Lima, Raquel T.; Seca, Hugo; Vasconcelos, M. Helena; Xavier, Cristina P. R.] Univ Porto, Canc Drug Resistance Grp, IPA TIMUP, Inst Mol Pathol & Immunol, Rua Campo Alegre 823, P-4100 Oporto, Portugal. [Seca, Hugo; Vasconcelos, M. Helena] Univ Porto, Dept Biol Sci, Fac Pharm, Rua Campo Alegre 823, P-4100 Oporto, Portugal. [Lima, Raquel T.] Univ Porto, Dept Pathol & Oncol, Fac Pharm, Rua Campo Alegre 823, P-4100 Oporto, Portugal. [Lima, Raquel T.; Seca, Hugo; Vasconcelos, M. Helena; Xavier, Cristina P. R.] Univ Porto, i3S, Rua Campo Alegre 823, P-4100 Oporto, Portugal. [Joubert, Annie M.; Nolte, Elsie Magdalena; Theron, Anne E.] Univ Pretoria, Dept Physiol, ZA-0002 Pretoria, Gauteng, South Africa. [Asselin, Eric] Univ Quebec Trois Rivieres, Dept Biol & Med, Trois Rivieres, PQ GA9 5H7, Canada. [Walker, Mark J.] Univ Queensland, Australian Infect Dis Res Ctr, Brisbane, Qld, Australia. [Walker, Mark J.] Sch Chem & Mol Biosci, Brisbane, Qld, Australia. [Wolvetang, Ernst J.] Univ Queensland, AIBN, Brisbane, Qld, Australia. [Manzoni, Claudia] Univ Reading, Sch Pharm, Reading, Berks, England. [Lewis, Patrick A.] Univ Reading, Sch Pharm, Whiteknights, Reading, Berks, England. [Brookes, Paul S.; Johnson, Gail V. W.] Univ Rochester, Med Ctr, Dept Anesthesiol, Rochester, NY 14642 USA. [Sparks, Janet D.] Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA. [Giordano, Antonio] Univ Siena, Dept Med Surg & Neurosci, Via Laterina 8, I-53100 Siena, Italy. [Sciarretta, Sebastiano] Univ Roma La Sapienza, Dept Med Surg Sci & Biotechnol, Latina, Italy. [Aquilano, Katia; Campello, Silvia; Ciriolo, Maria Rosa; Di Bartolomeo, Sabrina; Filomeni, Giuseppe; Barbato, Daniele Lettieri; Piacentini, Mauro] Univ Roma Tor Vergata, Dept Biol, Rome, Italy. [Schiavi, Alfonso] Univ Roma Tor Vergata, Dept Biomed & Prevent, Rome, Italy. [Franco, Rodrigo] Univ Roma Tor Vergata, Dept Chem, Rome, Italy. [Ozbun, Michelle A.] Univ Roma Tor Vergata, Dept Clin Sci & Translat Med, Rome, Italy. [Bernassola, Francesca] Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy. [Melino, Gerry] Univ Roma Tor Vergata, Dept Surg & Expt Med, Rome, Italy. [Di Daniele, Nicola; Federici, Massimo; Menghini, Rossella] Univ Roma Tor Vergata, Dept Syst Med, Rome, Italy. [Cecconi, Francesco; Corazzari, Marco] Univ Roma Tor Vergata, Dept Biol, Rome, Italy. [Sibirny, Andriy A.] Univ Rzeszow, Inst Biol, Rzeszow, Poland. [Dini, Luciana] Univ Salento, Dept Biol & Environm Sci & Technol, Lecce, Italy. [Fimia, Gian Maria] Univ Salento, Dept Biol & Environm Sci & Technol DiSTeBA, Lecce, Italy. [Iovane, Valentina] Univ Salento, Dept Pharm, Salerno, Italy. [Valente, Enza Maria] Univ Salento, Sect Neurosci, Dept Med & Surg, Salerno, Italy. [Machado-Santelli, Glaucia M.] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Sao Paulo, SP, Brazil. [Goncalves, Dawit A. P.; Kettelhut, Isis do Carmo; Machado, Juliano] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto, SP, Brazil. [Navegantes, Luiz C.; Silveira, Wilian A.] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Physiol, Ribeirao Preto, SP, Brazil. [Brum, Patricia Chakur; Jannig, Paulo Roberto] Univ Sao Paulo, Sch Phys Educ & Sport, Cellular & Mol Exercise Physiol Lab, Sao Paulo, Brazil. [Man, Na; Wen, Longping; Zhang, Yunjiao] Univ Sci & Technol China, Hefei, Anhui, Peoples R China. [Mei, Yide] Univ Sci & Technol China, CAS Key Lab Innate Immun & Chron Dis, Sch Lifesci, Hefei, Anhui, Peoples R China. [Shi, Qinghua] Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China. [Shi, Qinghua] Hefei Natl Lab Phys Sci Microscale, Hefei, Anhui, Peoples R China. [Wu, Mian] Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China. [Daza, Paula] Univ Seville, Dept Cell Biol, Seville, Spain. [Cordero, Mario D.] Univ Seville, Inst Biomed Sevilla IBIS, Dept Oral Med, Seville, Spain. [King, Jason S.] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England. [Boucher, Marie-Josee] Univ Sherbrooke, Fac Med & Sci St, Dept Med, Div Gastroenterol, Sherbrooke, PQ J1K 2R1, Canada. [Del Bello, Barbara; Maellaro, Emilia] Univ Siena, Dept Mol & Dev Med, Via Laterina 8, I-53100 Siena, Italy. [Poprawa, Izabela; Rost-Roszkowska, Magdalena] Univ Silesia, Dept Anim Histol & Embryol, Katowice, Poland. [Tan, Ming] Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36688 USA. [Kumar, Sharad] Univ S Australia, Adelaide, SA 5001, Australia. [Kumar, Sharad] Ctr Canc Biol, SA Pathol, Adelaide, SA, Australia. [Morrison, Janna L.] Univ S Australia, Early Origins Adult Hlth Res Grp, Sch Pharm & Med Sci, Sansom Inst Hlth Res, Adelaide, SA 5001, Australia. [Cui, Taixing; Fan, Daping] Univ S Carolina, Sch Med, Dept Cell Biol & Anat, Columbia, SC 29208 USA. [Ray, Swapan K.] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA. [Baumgarner, Bradley L.] Univers South Carolina Upstate, Dept Biol, Div Nat Sci & Engn, Spartanburg, SC USA. [Chatterjee, Saurabh] Univ S Carolina, Environm Hlth & Dis Lab, Dept Environm Hlth Sci, Columbia, SC 29208 USA. [Pattison, Scott] Univ S Dakota, Div Basic Biomed Sci, Vermillion, SD 57069 USA. [Wang, Hongmin] Univ S Dakota, Sanford Sch Med, Div Basic Biomed Sci, Vermillion, SD 57069 USA. [Wang, Xuejun] Univ S Dakota, Vermillion, SD 57069 USA. [Dickey, Chad A.] Univ S Florida, Byrd Alzheimers Inst, Tampa, FL USA. [Nanjundan, Meera] Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL USA. [Uversky, Vladimir N.] Univ S Florida, Dept Mol Med, Tampa, FL USA. [Zhou, Shu-Feng] Univ S Florida, Dept Pharmaceut Sci, Tampa, FL USA. [Jinwal, Umesh Kumar] Univ S Florida, Dept Pharmaceut Sci, Coll Pharm, Byrd Alzheimers Inst, Tampa, FL USA. [Cragg, Mark S.] Univ Southampton, Canc Sci, Southampton, Hants, England. [Tumbarello, David A.] Univ Southampton, Ctr Biol Sci, Highfield Campus, Southampton, Hants, England. [Jung, Jae U.; Liang, Chengyu; Ou, Jing-hsiung James; Schoenthal, Axel H.] Univ S Carolina, Dept Mol Microbiol & Immunol, Keck Sch Med, Los Angeles, CA USA. [Mariani, Francesca V.] Univ S Carolina, Eli & Edythe Broad, CIRM Ctr Regenerat Med & Stem Cell Res, Dept Cell & Neurobiol,Keck Sch Med, Los Angeles, CA USA. [Askanas, Valerie] Univ S Carolina, Keck Sch Med Neurol & Pathol, Los Angeles, CA USA. [Fernandez-Checa, Jose C.] Univ S Carolina, Res ALPD & Cirrhosis Ctr, Keck Sch Med, Los Angeles, CA USA. [Bouret, Sebastien G.] Univ S Carolina, Saban Res Inst, Dev Neurosci Program, Childrens Hosp Angeles, Los Angeles, CA USA. [Faergeman, Nils J.; Guerra, Barbara] Univ So Denmark, Villum Ctr Bioanalyt Sci, Dept Biochem & Mol Biol, Odense, Denmark. [Lucocq, John Milton] Andrews Univ, Sch Med, St Andrews, Fife, Scotland. [Coombs, Graham H.] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow, Lanark, Scotland. [Armstrong, Jane L.] Univ Sunderland, Dept Pharm Hlth & Wellbeing, Fac Sci Appl, Sunderland SR2 7EE, Durham, England. [Mihailidou, Anastasia Susie] Univ Sydney, Dept Cardiol, Sydney, NSW 2006, Australia. [Sue, Carolyn M.] Univ Sydney, Dept Neurogenet, Kolling Inst, St Leonards, NSW, Australia. [Bae, Dong-Hun; Gutierrez, Elaine; Jansson, Patric J.; Lane, Darius J. R.; Merlot, Angelica M.; Richardson, Des R.; Sahni, Sumit] Univ Sydney, Dept Pathol, Sydney, NSW 2006, Australia. [Bae, Dong-Hun; Gutierrez, Elaine; Jansson, Patric J.; Lane, Darius J. R.; Merlot, Angelica M.; Richardson, Des R.; Sahni, Sumit] Bosch Inst, Sydney, NSW, Australia. [Megyeri, Klara; Orosz, Laszlo] Univ Szeged, Dept Med Microbiol & Immunobiol, Szeged, Csongrad, Hungary. [Petrovski, Goran] Univ Szeged, Dept Ophthalmol, Fac Med, Szeged, Hungary. [Choubey, Vinay] Univ Tartu, Dept Pharmacol, Ulikooli 18, EE-50090 Tartu, Estonia. [Kaasik, Allen] Univ Tartu, Inst Biomed & Translat Med, Ulikooli 18, EE-50090 Tartu, Estonia. [Eri, Rajaraman; Randall-Demllo, Sarron] Univ Tasmania, Sch Hlth Sci, Launceston, Tas 7250, Australia. [Bridges, Dave] Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA. [Dalby, Kevin N.] Univ Texas Austin, Coll Pharm, Div Med Chem, Austin, TX 78712 USA. [Zhong, Qing] Univ Texas Dallas, Dept Biochem, Dallas, TX 75230 USA. [Dong, Xiaonan; Levine, Beth; Liu, Yang; Zhong, Qing] Univ Texas Dallas, SW Med Ctr, Dept Internal Med, Ctr Autophagy Res, Dallas, TX 75230 USA. [Teng, Ba-Bie] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Inst Mol Med, Houston, TX USA. [Jagannath, Chinnaswamy] Univ Texas Houston, Hlth Sci Ctr, Dept Pathol & Lab Med, Houston, TX USA. [Vigneswaran, Nadarajah] Univ Texas Houston, Hlth Sci Ctr, Sch Dent, Houston, TX USA. [Nawrocki, Steffan T.] Univ Texas San Antonio, Hlth Sci Ctr, CTRC Inst Drug Dev, San Antonio, TX USA. [Rao, Hai] Univ Texas San Antonio, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX USA. [Saikumar, Pothana] Univ Texas San Antonio, Hlth Sci Ctr, Dept Pathol, San Antonio, TX USA. [Kumar, Addanki Pratap] Univ Texas San Antonio, Hlth Sci Ctr, Dept Urol, San Antonio, TX USA. [Venkatachalam, Kartik] Univ Texas San Antonio, Hlth Sci Ctr UTHSC, Dept Urol, Dept Integrat Biol & Pharmacol, San Antonio, TX USA. [Lorenzi, Philip L.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, 1515 Holcombe Blvd, Houston, TX 77030 USA. [Liu, Xian-De] Univ Texas Houston, MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. [Young, Ken H.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Hematopathol, 1515 Holcombe Blvd, Houston, TX 77030 USA. 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Zhang, David/0000-0002-5027-5286; Awale, Suresh/0000-0002-5299-193X; Braus, Gerhard/0000-0002-3117-5626; Folini, Marco/0000-0002-1811-4407; Fan, Chunhai/0000-0002-7171-7338; Juhasz, Gabor/0000-0001-8548-8874; Wang, Yu Tian/0000-0001-8592-0698; Minina, Elena/0000-0002-2619-1859; Dubey, Vikash/0000-0002-4281-2504; Garg, Abhishek/0000-0002-9976-9922; Andrieu-Abadie, Nathalie/0000-0003-2698-1970; Hill, Bradford/0000-0001-5332-8286; AUBERGER, Patrick/0000-0002-2481-8275; Chagin, Andrei/0000-0002-2696-5850; Stork, Bjorn/0000-0002-4167-7806; MECHTA-GRIGORIOU, Fatima/0000-0002-3751-6989; Cassinelli, Giuliana/0000-0003-4648-2562; Uversky, Vladimir/0000-0002-4037-5857; Harrath, Abdel Halim/0000-0002-2170-1303; Torgersen, Maria Lyngaas/0000-0003-2616-7194; Lee, Ju-hyun/0000-0002-0280-8375; Cleyrat, Cedric/0000-0002-1928-6497; Pinto Ribeiro Xavier, Cristina/0000-0002-4613-1917; Hernandez, Agustin/0000-0002-7884-8023; Frankel, Lisa/0000-0001-7249-3607; Saveljeva, Svetlana/0000-0002-0644-9752; malorni, walter/0000-0002-1223-7000; Rouschop, Kasper/0000-0002-4208-5415; MORELLI, MARIA BEATRICE/0000-0002-4614-5649; Wright, Karen/0000-0003-0040-9247; Wilkinson, Simon/0000-0003-1082-8218; Bryson-Richardson, Robert/0000-0002-9501-8208; Balduini, Walter/0000-0001-8438-9559; Wang, Xuejun/0000-0001-9267-1343; Vieira, Helena/0000-0001-9415-3742; Matsuura, Akira/0000-0002-2300-7227; Rizzi, Federica/0000-0002-6670-2588; pierre, philippe/0000-0003-0863-8255; McInerney, Gerald/0000-0003-2257-7241; Tripathi, Durga/0000-0001-8736-4808; Isidoro, Ciro/0000-0002-5494-3034; Nunes dos Santos, Claudia/0000-0002-5809-1924; Pereira, Paulo/0000-0002-9908-2290; Ureshino, Rodrigo/0000-0003-3371-3376; Cadwell, Ken/0000-0002-5860-0661; BRANCOLINI, Claudio/0000-0002-6597-5373; Sigurdsson, Einar/0000-0003-1451-0952; Duchen, Michael/0000-0003-2548-4294; Amelio, Ivano/0000-0002-9126-5391; Malli, Roland/0000-0001-6327-8729; Zhou, Guang-Zhou/0000-0003-3672-875X; Martens, Sascha/0000-0003-3786-8199; Gavard, Julie/0000-0002-7985-9007; Rosenstiel, Philip/0000-0002-9692-8828; Linkermann, Andreas/0000-0001-6287-9725; Lanzi, Cinzia/0000-0002-4480-9413; Hoppe, Thorsten/0000-0002-4734-9352; MOREL, Etienne/0000-0002-4763-4954; Kwok, Terry/0000-0002-5905-3233; Simonsen, Anne/0000-0003-4711-7057; Cecconi, Francesco/0000-0002-5614-4359; Harris, James/0000-0002-5634-9637; Romani, Luigina/0000-0002-1356-525X; Velasco, Guillermo/0000-0002-1994-2386; Chieppa, Marcello/0000-0001-9819-0823; Frigo, Daniel/0000-0002-0713-471X; Olsson, Stefan/0000-0003-1931-9081; Cocco, Tiziana/0000-0001-7171-3460; Chang, Chih-Peng/0000-0002-0061-3478; Dikic, Ivan/0000-0001-8156-9511; Norga, Koenraad/0000-0002-9231-0350; Harris, Adrian/0000-0003-1376-8409; Rein, Theo/0000-0003-2850-4289; Kaminskyy, Vitaliy/0000-0002-8151-5270; Qi, Xin/0000-0002-9578-3890; Shiri-Sverdlov, Ronit/0000-0002-6736-7814; Schiavi, Alfonso/0000-0002-6563-8035; Ketteler, Robin/0000-0002-2786-7291; Salazar, Maria/0000-0001-6784-9541; CRIPPA, VALERIA/0000-0002-3058-5711; Wu, Jian/0000-0001-9933-7364; Hilfiker, Sabine/0000-0002-5167-7682; Hulmi, Juha/0000-0003-3813-2124; Fernandez-Checa, Jose Carlos/0000-0003-3422-2990; Wong, Esther/0000-0003-2421-7346; Rudolf, Ruediger/0000-0002-0833-1053; Zhu, Wei-Guo/0000-0001-8385-6581; Winklhofer, Konstanze/0000-0002-7256-8231; Fearnhead, Howard/0000-0002-8054-9794; Sahni, Sumit/0000-0002-2900-8845; Clementi, Emilio/0000-0001-7333-8270; , Carmen/0000-0002-2652-6102; Kalia, Manjula/0000-0002-3376-3659; Cianfanelli, Valentina/0000-0002-3857-9463; Chen, Quan/0000-0001-7539-8728; antonioli, manuela/0000-0002-7568-4713; Yamanaka, Koji/0000-0003-4655-0035; Sedej, Simon/0000-0002-4419-6821; Guerra, Barbara/0000-0003-1136-2413; MacIntosh, Gustavo/0000-0003-1350-1229; Hamann, Andrea/0000-0001-9821-7491; Moris, Arnaud/0000-0002-5052-1678; Bravo-San Pedro, Jose Manuel/0000-0002-5781-1133 FU BLRD VA [I01 BX001746, I01 BX001969]; Biotechnology and Biological Sciences Research Council [BBS/E/B/000C0413]; Cancer Research UK [11359, 12825, 12918]; Doris Duke Charitable Foundation [2014112]; Medical Research Council [G0300648, G0601891, G0801936, G1000089, G1002186, MC_U105185860, MC_U132670600, MC_UP_A500_1019, MC_UU_12016/4, MC_UU_12022/6, MR/J010448/1, MR/L010933/1, MR/M00869X/1, MR/M019217/1, MR/N004434/1]; NCCIH NIH HHS [R01 AT005076]; NCI NIH HHS [K08 CA164047, K08 CA193982, K22 CA181274, P01 CA163200, P30 CA010815, R01 CA078810, R01 CA089121, R01 CA130893, R01 CA140964, R01 CA142862, R01 CA143811, R01 CA162405, R01 CA184137, R01 CA187305, R01 CA193698, T32 CA009686, U54 CA149147]; NCRR NIH HHS [P20 RR024489]; NEI NIH HHS [R01 EY005681, R01 EY009083, R01 EY010199, R01 EY013434, R01 EY015537, R01 EY018884, R01 EY019643, R01 EY022633, R01 EY023512, R01 EY024327, R01 EY025362, R21 EY026207]; NHLBI NIH HHS [P01 HL129941, R01 HL056416, R01 HL059888, R01 HL071158, R01 HL072166, R01 HL072844, R01 HL079669, R01 HL098216, R01 HL107594, R01 HL117913, R01 HL126711, R01 HL130174, R01 HL130230, R01 HL130845, R56 HL122580]; NIA NIH HHS [K02 AG042095, P01 AG031782, P30 AG028740, R00 AG042494, R00 AG048016, R01 AG020197, R01 AG031867, R01 AG032611, R01 AG038664, R01 AG039756, R01 AG043517, R37 AG021904]; NIAAA NIH HHS [K01 AA019996, R01 AA019954, R01 AA022601]; NIAID NIH HHS [R01 AI042999, R01 AI091968, R01 AI092084, R01 AI103197, R01 AI104928, R01 AI108906, R01 AI111935, R21 AI115286]; NIAMS NIH HHS [R01 AR042527, R01 AR050429, R01 AR060837, R01 AR062030, R21 AR060444]; NICHD NIH HHS [U54 HD090255]; NIDDK NIH HHS [K01 DK075386, K08 DK089117, P01 DK098108, P30 DK020541, P30 DK020572, P30 DK020593, R00 DK094980, R01 DK033823, R01 DK044234, R01 DK061498, R01 DK062092, R01 DK073336, R01 DK076685, R01 DK079879, R01 DK090115, R01 DK097441, R01 DK098331, R01 DK105118, R01 DK107220, R03 DK089010, R03 DK106304, R03 DK106344, R21 DK075494, R56 DK037034, R56 DK108921]; NIEHS NIH HHS [P30 ES006694, P30 ES023512]; NIGMS NIH HHS [GM053396, K12 GM068524, P20 GM103492, P20 GM103554, P20 GM103652, P20 GM104934, R01 GM021841, R01 GM053396, R01 GM060574, R01 GM061766, R01 GM063075, R01 GM101056, R01 GM114840, R01 GM116908]; NINDS NIH HHS [K08 NS083739, K08 NS085324, R01 NS062792, R01 NS073813, R01 NS075685, R01 NS076896, R01 NS077239, R01 NS078072, R01 NS079697, R01 NS085070, R01 NS088192, R01 NS089737, R01 NS091218, R01 NS094527, R03 NS090939, R21 NS091928]; Parkinson's UK [F-1002, H-1201, K-1202]; Wellcome Trust [087518]; Worldwide Cancer Research [14-1328] NR 2174 TC 332 Z9 341 U1 551 U2 938 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PY 2016 VL 12 IS 1 BP 1 EP 222 DI 10.1080/15548627.2015.1100356 PG 222 WC Cell Biology SC Cell Biology GA DI6FU UT WOS:000373595400001 PM 26799652 ER PT J AU Nath, A Wood, C AF Nath, Avi Wood, Charles TI Preface SO CURRENT HIV RESEARCH LA English DT Editorial Material C1 [Nath, Avi] NINDS, NIH, Bldg 10,Room 7C103 10 Ctr Dr, Bethesda, MD 20892 USA. [Wood, Charles] Univ Nebraska, Nebraska Ctr Virol, Lincoln Morrison Ctr 102C, 4240 Fair St, Lincoln, NE 68583 USA. RP Nath, A (reprint author), NINDS, NIH, Bldg 10,Room 7C103 10 Ctr Dr, Bethesda, MD 20892 USA.; Wood, C (reprint author), Univ Nebraska, Nebraska Ctr Virol, Lincoln Morrison Ctr 102C, 4240 Fair St, Lincoln, NE 68583 USA. EM natha@mail.nih.gov; cwood1@unl.edu NR 0 TC 0 Z9 0 U1 2 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-162X EI 1873-4251 J9 CURR HIV RES JI Curr. HIV Res. PY 2016 VL 14 IS 2 BP 82 EP 82 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DI7YC UT WOS:000373716900001 ER PT J AU Siniscalchi, A Sztajzel, R Bonci, A Malferrari, G De Sarro, G Gallelli, L AF Siniscalchi, Antonio Sztajzel, Roman Bonci, Antonello Malferrari, Giovanni De Sarro, Giovambattista Gallelli, Luca TI Cocaine and Cerebral Small Vessel: Is it a Negative Factor for Intravenous Thrombolysis? SO CURRENT VASCULAR PHARMACOLOGY LA English DT Editorial Material ID TISSUE-PLASMINOGEN ACTIVATOR; ACUTE ISCHEMIC-STROKE; INTRACEREBRAL HEMORRHAGE; RISK-FACTORS; BLOOD-FLOW; MANAGEMENT; BALTIMORE; DYNAMICS C1 [Siniscalchi, Antonio] Annunziata Hosp, Dept Neurol, Via F Migliori 1, I-87100 Cosenza, Italy. [Sztajzel, Roman] Univ Hosp Geneva, Dept Neurol, Geneva, Switzerland. [Bonci, Antonello] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Malferrari, Giovanni] Santa Maria Nuova Hosp, Dept Neurol, Reggio Emilia, Italy. [De Sarro, Giovambattista; Gallelli, Luca] Univ Catanzaro, Clin Pharmacol Unit, Mater Domini Univ Hosp, Chair Pharmacol,Dept Hlth Sci,Sch Med, Catanzaro, Italy. RP Siniscalchi, A (reprint author), Annunziata Hosp, Dept Neurol, Via F Migliori 1, I-87100 Cosenza, Italy. EM anto.siniscalchi@libero.it RI De Sarro, Giovambattista/G-5256-2010 NR 32 TC 2 Z9 2 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-1611 EI 1875-6212 J9 CURR VASC PHARMACOL JI Current Vascular Pharmacology PY 2016 VL 14 IS 3 BP 304 EP 306 DI 10.2174/1570161114999160204151620 PG 3 WC Pharmacology & Pharmacy; Peripheral Vascular Disease SC Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA DI7WO UT WOS:000373712900012 PM 26845684 ER PT J AU Rawstron, AC Paiva, B Stetler-Stevenson, M AF Rawstron, Andy C. Paiva, Bruno Stetler-Stevenson, Maryalice TI Assessment of Minimal Residual Disease in Myeloma and the Need for a Consensus Approach SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE plasma cell myeloma; minimal residual disease; PCR; flow cytometry; high throughput sequencing; quantification; rare event detection ID MULTIPARAMETER FLOW-CYTOMETRY; TIME QUANTITATIVE PCR; DIAGNOSED MULTIPLE-MYELOMA; STEM-CELL TRANSPLANTATION; CIRCULATING PLASMA-CELLS; PROGNOSTIC VALUE; PREDICTS; SURVIVAL; DISORDERS; MGUS AB Treatment options for myeloma continue to develop at a rapid pace, and it is becoming increasingly challenging to determine the optimal therapeutic approaches because demonstrating a clear survival benefit now requires many years of follow-up. The detection of minimal residual disease (MRD) is recognized as a sensitive and rapid approach to evaluate treatment efficacy that predicts progression-free and overall survival independent of categorical response assessment and patients' biology. The benefit of MRD analysis is reflected in the many different techniques (multiparameter flow cytometry, quantitative polymerase chain reaction, and high-throughput sequencing) and collaborative groups (including EMN, ESCCA, ICCS, Euro-Flow, and EuroMRD) that have performed collaborative projects to harmonize quantitative MRD detection. The time has come to adopt a consensus approach, and this report reviews the benefits and disadvantages of different strategies for MRD detection in myeloma and highlights the requirements for a sensitive, reproducible, and clinically meaningful cellular analytical approach. (C) 2015 International Clinical Cytometry Society C1 [Rawstron, Andy C.] Leeds Teaching Hosp NHS Trust, HMDS, Leeds, W Yorkshire, England. [Rawstron, Andy C.] European Soc Clin Cell Anal, Rome, Italy. [Paiva, Bruno] Univ Navarra Clin, Pamplona, Spain. [Paiva, Bruno] Ctr Invest Med Aplicada, Pamplona, Spain. [Paiva, Bruno] Inst Invest Sanitaria Navarra, Pamplona, Spain. [Stetler-Stevenson, Maryalice] NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA. RP Rawstron, AC (reprint author), Leeds Teaching Hosp NHS Trust, HMDS, Leeds, W Yorkshire, England.; Rawstron, AC (reprint author), European Soc Clin Cell Anal, Rome, Italy. EM andy.rawstron@hmds.org.uk OI Rawstron, Andy/0000-0003-0798-9790 NR 31 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 EI 1552-4957 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JAN PY 2016 VL 90 IS 1 SI SI BP 21 EP 25 DI 10.1002/cyto.b.21272 PG 5 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA DI3EK UT WOS:000373381000004 PM 26202864 ER PT J AU Stetler-Stevenson, M Paiva, B Stoolman, L Lin, P Jorgensen, JL Orfao, A Van Dongen, J Rawstron, AC AF Stetler-Stevenson, Maryalice Paiva, Bruno Stoolman, Lloyd Lin, Pei Jorgensen, Jeffrey L. Orfao, Alberto Van Dongen, Jacques Rawstron, Andy C. TI Consensus Guidelines for Myeloma Minimal Residual Disease Sample Staining and Data Acquisition SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE myeloma; minimal residual disease; flow cytometry ID NORMAL PLASMA-CELLS; ASSAYS PRACTICE GUIDELINES; MULTIPLE-MYELOMA; FLOW-CYTOMETRY; BONE-MARROW; VALIDATION; STANDARDIZATION; HETEROGENEITY; EXPRESSION; DISORDERS AB Background: Flow cytometric (FC) detection of minimal residual disease (MRD) in multiple myeloma (MM) is prognostic and predictive of response to therapy. Therefore, standardization of FC MM MRD testing is vital to ensure better and uniform assessment of response to therapy and clinical prognostication. The International Clinical Cytometry Society and European Society for Clinical Cell Analysis, recognizing the need for standardized FC approaches, organized a working group to develop consensus guidelines on good clinical practice in FC MM MRD. Consensus guidelines are presented for specimen quality, staining process, reagent combinations, and the data acquisition process, all key factors in achieving high quality FC MM MRD testing. Methods: A group of eight flow cytometrists currently performing FC testing in MM evaluated available literature on FC MM MRD testing. A document presenting best practice was developed and reviewed in successive rounds until consensus was reached. Results/Conclusion: The consensus on best practice for detection of MRD in MM is that CD38, CD138, and CD45 are analyzed in combination with CD19, CD56, CD27, CD81, and CD117. Consensus guidelines on acceptable specimen quality, staining procedures, panel design, and data acquisition were developed. (C) 2015 International Clinical Cytometry Society C1 [Stetler-Stevenson, Maryalice] NCI, Pathol Lab, NIH, Bldg 10,Room 2A-33,Mail Stop 1500, Bethesda, MD 20892 USA. [Paiva, Bruno] Univ Navarra Clin, Ctr Invest Med Aplicadas, IDISNA, SpainAv Pio 12 55, Pamplona, Spain. [Stoolman, Lloyd] Univ Michigan Hlth Syst, Dept Pathol, Ann Arbor, MI 48109 USA. [Lin, Pei; Jorgensen, Jeffrey L.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Orfao, Alberto] Univ Salamanca IBSAL, Canc Res Ctr IBMCC CSIC USAL, Salamanca, Spain. [Orfao, Alberto] Univ Salamanca IBSAL, Cytometry Serv, Dept Med, Salamanca, Spain. [Van Dongen, Jacques] Erasmus MC, Dept Immunol, Rotterdam, Netherlands. [Rawstron, Andy C.] Jamess Inst Oncol, Dept Haematol, HMDS, Leeds LS9 7TF, W Yorkshire, England. RP Stetler-Stevenson, M (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A-33,Mail Stop 1500, Bethesda, MD 20892 USA. EM Stetler@Mail.Nih.Gov OI Rawstron, Andy/0000-0003-0798-9790 NR 23 TC 3 Z9 3 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 EI 1552-4957 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JAN PY 2016 VL 90 IS 1 SI SI BP 26 EP 30 DI 10.1002/cyto.b.21249 PG 5 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA DI3EK UT WOS:000373381000005 PM 25907102 ER PT J AU Arroz, M Came, N Lin, P Chen, WN Yuan, C Lagoo, A Monreal, M de Tute, R Vergilio, JA Rawstron, AC Paiva, B AF Arroz, Maria Came, Neil Lin, Pei Chen, Weina Yuan, Constance Lagoo, Anand Monreal, Mariela de Tute, Ruth Vergilio, Jo-Anne Rawstron, Andy C. Paiva, Bruno TI Consensus Guidelines on Plasma Cell Myeloma Minimal Residual Disease Analysis and Reporting SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE plasma cell myeloma; minimal residual disease; flow cytometry ID MULTIPARAMETER FLOW-CYTOMETRY; MULTIPLE-MYELOMA; TRANSPLANTATION; SENSITIVITY; DISORDERS; ISSUES AB Background: Major heterogeneity between laboratories in flow cytometry (FC) minimal residual disease (MRD) testing in multiple myeloma (MM) must be overcome. Cytometry societies such as the International Clinical Cytometry Society and the European Society for Clinical Cell Analysis recognize a strong need to establish minimally acceptable requirements and recommendations to perform such complex testing. Methods: A group of 11 flow cytometrists currently performing FC testing in MM using different instrumentation, panel designs (>= 6-color) and analysis software compared the procedures between their respective laboratories and reviewed the literature to propose a consensus guideline on flow-MRD analysis and reporting in MM. Results/Conclusion: Consensus guidelines support i) the use of minimum of five initial gating parameters (CD38, CD138, CD45, forward, and sideward light scatter) within the same aliquot for accurate identification of the total plasma cell compartment; ii) the analysis of potentially aberrant phenotypic markers and to report the antigen expression pattern on neoplastic plasma cells as being reduced, normal or increased, when compared to a normal reference plasma cell immunophenotype (obtained using the same instrument and parameters); and iii) the percentage of total bone marrow plasma cells plus the percentages of both normal and neoplastic plasma cells within the total bone marrow plasma cell compartment, and over total bone marrow cells. Consensus guidelines on minimal current and future MRD analyses should target a lower limit of detection of 0.001%, and ideally a limit of quantification of 0.001%, which requires at least 3 X 10(6) and 5 X 10(6) bone marrow cells to be measured, respectively. (C) 2015 International Clinical Cytometry Society C1 [Arroz, Maria] Hosp S Francisco Xavier, Cytometry Lab, Dept Clin Pathol, CHLO, Estr Ft Alto Duque, P-1495005 Lisbon, Portugal. [Came, Neil] Peter MacCallum Canc Ctr, Dept Pathol, Melbourne, Vic, Australia. [Lin, Pei] Univ Texas Houston, MD Anderson Canc Ctr, Dept Hematopathol, 1515 Holcombe Blvd, Houston, TX 77030 USA. [Chen, Weina] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Yuan, Constance] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. [Lagoo, Anand] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Monreal, Mariela] Interpflow Corp, Miami, FL USA. [de Tute, Ruth; Rawstron, Andy C.] St Jamess Inst Oncol, Dept Haematol, HMDS, Leeds, W Yorkshire, England. [Vergilio, Jo-Anne] Univ Michigan, Med Ctr, Hematol Oncol Lab, Ann Arbor, MI USA. [Paiva, Bruno] Univ Navarra, Univ Navarra Clin, Ctr Invest Med Aplicada, E-31080 Pamplona, Spain. RP Arroz, M (reprint author), Hosp S Francisco Xavier, Cytometry Lab, Dept Clin Pathol, CHLO, Estr Ft Alto Duque, P-1495005 Lisbon, Portugal. EM marroz@chlo.min-saude.pt OI Rawstron, Andy/0000-0003-0798-9790 NR 29 TC 6 Z9 6 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 EI 1552-4957 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JAN PY 2016 VL 90 IS 1 SI SI BP 31 EP 39 DI 10.1002/cyto.b.21228 PG 9 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA DI3EK UT WOS:000373381000006 PM 25619868 ER PT J AU Healy, MW Patounakis, G Connell, MT Devine, K DeCherney, AH Levy, MJ Hill, MJ AF Healy, Mae Wu Patounakis, George Connell, Matt T. Devine, Kate DeCherney, Alan H. Levy, Michael J. Hill, Micah J. TI Does a frozen embryo transfer ameliorate the effect of elevated progesterone seen in fresh transfer cycles? SO FERTILITY AND STERILITY LA English DT Article DE Elevated progesterone; fresh transfer versus FET cycles; live birth ID IN-VITRO FERTILIZATION; PREGNANCY RATES; ENDOMETRIAL RECEPTIVITY; PLASMA PROGESTERONE; OVARIAN STIMULATION; FOLLICULAR PHASE; HORMONE AGONIST; LIVE BIRTH; GONADOTROPIN; RISE AB Objective: To compare the effect of progesterone (P) on the day of trigger in fresh assisted reproduction technology (ART) transfer cycles versus its effect on subsequent frozen embryo transfer (FET) cycles. Design: Retrospective cohort study. Setting: Large private ART practice. Patient(s): Fresh autologous and FET cycles from 2011-2013. Intervention(s): None. Main Outcome Measure(s): Live birth. Result(s): A paired analysis of patients who underwent both a fresh transfer and subsequent FET cycle and an unpaired analysis of data from all fresh transfer cycles and all FET cycles were performed. We analyzed 1,216 paired and 4,124 unpaired cycles, and P was negatively associated with birth in fresh but not FET cycles in all analyses. Interaction testing of P and cycle type indicated P had a different association with birth in fresh versus FET cycles. When P was >= 2 ng/mL at the time of trigger, live birth was more likely in FET versus fresh cycles in the paired analysis (47% vs. 10%), in the unpaired analysis (51% vs. 14%), and in unpaired, good blastocyst only transfer subgroup (51% vs. 29%). Live birth was similar in FET cycles, with P >= 2 ng/mL versus P < 2 ng/mL (51% vs. 49%). Conversely, live birth was lower in fresh cycles, with P >= 2 ng/mL versus P < 2 ng/mL (15% vs. 45%). Conclusion(s): Elevated P levels on the day of trigger during the initial fresh cycle were negatively associated with live birth in the fresh transfer cycles but not in subsequent FET cycles. Freezing embryos and performing a subsequent FET cycle ameliorates the effect of elevated P on live-birth rates. (C) 2016 by American Society for Reproductive Medicine. C1 [Healy, Mae Wu; Patounakis, George; Connell, Matt T.; Devine, Kate; DeCherney, Alan H.; Hill, Micah J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Devine, Kate; Levy, Michael J.; Hill, Micah J.] Shady Grove Fertil Sci Ctr, Rockville, MD USA. RP Healy, MW (reprint author), 10 Ctr Dr, Bethesda, MD 20876 USA. EM mae.healy@mail.nih.gov OI Hill, Micah/0000-0002-3104-7763 FU Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This research was supported in part by the Intramural Research Program of the Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The views expressed in this manuscript are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U. S. Government. NR 26 TC 6 Z9 6 U1 1 U2 2 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 JAN PY 2016 VL 105 IS 1 BP 93 EP + DI 10.1016/j.fertnstert.2015.09.015 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DI3MK UT WOS:000373402600017 PM 26453267 ER PT J AU Malik, M Britten, J Cox, J Patel, A Catherino, WH AF Malik, Minnie Britten, Joy Cox, Jeris Patel, Amrita Catherino, William H. TI Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones SO FERTILITY AND STERILITY LA English DT Article DE Uterine leiomyoma 3D culture; gonadal hormones; leuprolide acetate; cetrorelix acetate; extracellular matrix ID ESTROGEN-RECEPTOR-ALPHA; HUMAN UTERINE LEIOMYOMA; AFRICAN-AMERICAN WOMEN; MITOGEN-ACTIVATED PROTEIN; ULIPRISTAL ACETATE; LEUPROLIDE ACETATE; GNRH AGONIST; MODULATOR ASOPRISNIL; CELL-PROLIFERATION; CETRORELIX ACETATE AB Objective: To determine the effect of GnRH analogues (GnRH-a) leuprolide acetate (LA) and cetrorelix acetate on gonadal hormone-regulated expression of extracellular matrix in uterine leiomyoma three-dimensional (3D) cultures. Design: Laboratory study. Setting: University research laboratory. Patient(s): Women undergoing hysterectomy for symptomatic leiomyomas. Intervention(s): The 3D cell cultures, protein analysis, Western blot, immunohistochemistry. Main Outcome Measure(s): Expression of extracellular matrix proteins, collagen 1, fibronectin, and versican in leiomyoma cells 3D cultures exposed to E-2, P, LA, cetrorelix acetate, and combinations for 24- and 72-hour time points. Result(s): The 3D leiomyoma cultures exposed to E2 for 24 hours demonstrated an increased expression of collagen-1 and fibronectin, which was maintained for up to 72 hours, a time point at which versican was up-regulated significantly. Although P up-regulated collagen-1 protein (1.29 +/- 0.04) within 24 hours of exposure, significant increase in all extracellular matrix (ECM) proteins was observed when the gonadal hormones were used concomitantly. Significant decrease in the amount of ECM proteins was observed on use of GnRH-a, LA and cetrorelix, with 24-hour exposure. Both the compounds also significantly decreased ECM protein concentration despite the presence of E-2 or both gonadal hormones. Conclusion(s): This study demonstrates that GnRH-a directly affect the gonadal hormone-regulated collagen-1, fibronectin, and versican production in their presence. These findings suggest that localized therapy with GnRH-a may inhibit leiomyoma growth even in the presence of endogenous gonadal hormone exposure, thereby providing a mechanism to eliminate the hypoestrogenic side effects associated with GnRH-a therapy. (C) 2016 by American Society for Reproductive Medicine. C1 [Malik, Minnie; Britten, Joy; Cox, Jeris; Patel, Amrita; Catherino, William H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bldg A,Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. [Cox, Jeris; Catherino, William H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bldg A,Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM william.catherino@usuhs.edu OI Malik, Minnie/0000-0003-1129-6575 FU Bayer Schering Pharma; American Society for Reproductive Medicine; Abbvie Pharmaceuticals; American Board of Obstetrics and Gynecology; Kantar Health; Uniformed Services University of the Health Sciences; Eunice Kennedy Shriver National Institute of Child Health and Human Development [R21 HD070152-01A1]; Ferring Pharmaceuticals; EMD Serono Inc. FX M.M. has nothing to disclose. J.B. has nothing to disclose. J.C. has nothing to disclose. A.P. has nothing to disclose. W.H.C. reports grants from Bayer Schering Pharma; personal fees from American Society for Reproductive Medicine, Abbvie Pharmaceuticals, American Board of Obstetrics and Gynecology, and Kantar Health; personal fees from multiple sites as a Grand Rounds speaker, multiple sites; and his wife is an employee of Recombine (genetic testing, not related to leiomyomas or gonadal hormones).; Supported by grants from the Uniformed Services University of the Health Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development R21 HD070152-01A1, Ferring Pharmaceuticals, and EMD Serono Inc. NR 72 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2016 VL 105 IS 1 BP 214 EP 224 DI 10.1016/j.fertnstert.2015.09.006 PG 11 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DI3MK UT WOS:000373402600033 PM 26409322 ER PT J AU Foerster, C Koshiol, J Guerrero, AR Kogan, MJ Ferreccio, C AF Foerster, Claudia Koshiol, Jill Guerrero, Ariel R. Kogan, Marcelo J. Ferreccio, Catterina TI The case for aflatoxins in the causal chain of gallbladder cancer SO MEDICAL HYPOTHESES LA English DT Article ID HEPATITIS-B-VIRUS; HIGH-RISK AREA; HEPATOCELLULAR-CARCINOMA; GALLSTONE DISEASE; OCCUPATIONAL-EXPOSURE; DEVELOPING-COUNTRIES; CHILI-PEPPER; ENDEMIC AREA; BILE-ACID; ASSOCIATION AB Chronic aflatoxin exposure has long been related to hepatocellular carcinoma (HCC). Recently, its association with gallbladder cancer (GBC) was postulated. Here we present the data supporting this hypothesis in Chile, the country with the highest GBC mortality worldwide with age-standardized mortality rates (ASMR) of 10.3 in women and 5.04 in men. The highest GBC rates occur in Southern Chile (ASMR = 18), characterized by: high Amerindian ancestry, associated with high bile acid synthesis and gallstones; high poverty and high cereal agriculture, both associated with aflatoxin exposure. Afiatoxins have been detected in imported and locally grown foods items. We estimated population dietary exposure ranging from 0.25 to 35.0 ng/kg-body weight/day. The only report on human exposure in Chile found significantly more aflatoxin biomarkers in GBC than in controls (Odds Ratio = 13.0). The hypothesis of aflatoxin-GBC causal link in the Chilean population is supported by: genetically determined rapid cholesterol excretion and high gallstones prevalence (49.4%); low prevalence of HCC (ASMR = 4.9) and low HBV infection (0.15%) the main co-factor of aflatoxins in HCC risk. If the association between aflatoxins and GBC were confirmed, public health interventions based on food regulation could have a substantial public health impact. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Foerster, Claudia; Ferreccio, Catterina] Pontificia Univ Catolica Chile, Sch Med, Dept Publ Hlth, Marcoleta 434, Santiago, Chile. [Foerster, Claudia; Guerrero, Ariel R.; Kogan, Marcelo J.; Ferreccio, Catterina] FONDAP, Adv Ctr Chron Dis ACCDiS, Santiago, Chile. [Koshiol, Jill] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Guerrero, Ariel R.; Kogan, Marcelo J.] Univ Chile, Dept Pharmacol & Toxicol Chem, Pharmaceut & Chem Sci Fac, Santiago, Chile. RP Ferreccio, C (reprint author), Pontificia Univ Catolica Chile, Sch Med, Dept Publ Hlth, Marcoleta 434, Santiago, Chile. EM cferrec@med.puc.cl RI Guerrero, Ariel/A-1395-2012 OI Guerrero, Ariel/0000-0002-0676-7064 FU ACCDiS/FONDAP [15130011] FX ACCDiS/FONDAP #15130011. NR 84 TC 1 Z9 1 U1 2 U2 17 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 EI 1532-2777 J9 MED HYPOTHESES JI Med. Hypotheses PD JAN PY 2016 VL 86 BP 47 EP 52 DI 10.1016/j.mehy.2015.11.026 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DI1FN UT WOS:000373242100009 PM 26804596 ER PT J AU Mushtaq, G Greig, NH Anwar, F Zamzami, MA Choudhry, H Shaik, MM Tamargo, IA Kamal, MA AF Mushtaq, Gohar Greig, Nigel H. Anwar, Firoz Zamzami, Mazin A. Choudhry, Hani Shaik, Munvar M. Tamargo, Ian A. Kamal, Mohammad A. TI miRNAs as Circulating Biomarkers for Alzheimer's Disease and Parkinson's Disease SO MEDICINAL CHEMISTRY LA English DT Article DE Alzheimer's disease; beta-amyloid; alpha-synuclein; biofluids; diagnostic biomarkers; miRNAs; Parkinson's disease ID ALPHA-SYNUCLEIN EXPRESSION; NEURODEGENERATIVE DISEASES; CEREBROSPINAL-FLUID; EARLY-DIAGNOSIS; MICRORNAS; BRAIN; IDENTIFICATION; PROTEIN; DISORDERS; CELLS AB Detection of biomarkers for neurodegenerative disorders (NDDs) within brain tissues of Alzheimer's disease (AD) and Parkinson's disease (PD) patients has always been hampered by our inability to access and biopsy tissue of key brain regions implicated in disease occurrence and progression. Currently, diagnosis of NDDs is principally based on clinical observations of symptoms that present at later stages of disease progression, followed by neuroimaging and, possibly, CSF evaluation. One way to potentially detect and diagnose NDDs at a far earlier stage is to screen for abnormal levels of specific disease markers within the peripheral circulation of patients with NDDs. Increasing evidence suggests that there is dysregulation of microRNAs (miRNAs) in NDDs. Peripheral blood mononuclear cells, as well as biofluids, such as plasma, serum, urine and cerebrospinal fluid, contain miRNAs that can be identified and quantified. Circulating miRNAs within blood and other biofluids may thus be characterized and used as non-invasive, diagnostic biomarkers that facilitate the early detection of disease and potentially the continual monitoring of disease progression for NDDs such as AD and PD. Plainly, such a screen is only possible with a clear understanding of which miRNAs change with disease, and when these changes occur during the progression of AD and PD. Such information is becoming increasingly available and, in the near future, may not only support disease diagnosis, but provide the opportunity to evaluate therapeutic interventions earlier in the disease process. C1 [Mushtaq, Gohar; Anwar, Firoz; Zamzami, Mazin A.; Choudhry, Hani] King Abdulaziz Univ, Coll Sci, Dept Biochem, Jeddah 21413, Saudi Arabia. [Greig, Nigel H.; Tamargo, Ian A.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. [Shaik, Munvar M.] Univ Sains Malaysia, Sch Med Sci, Ctr Human Genome, Kubang Kerian 16150, Kelantan, Malaysia. [Kamal, Mohammad A.] King Abdulaziz Univ, King Fahd Med Res Ctr, POB 80216, Jeddah 21589, Saudi Arabia. [Kamal, Mohammad A.] Enzymoics, 7 Peterlee Pl, Hebersham, NSW 2770, Australia. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. EM greign@mail.nih.gov RI Zamzami, Mazin/D-9101-2017; OI Kamal, Mohammad Amjad/0000-0003-0088-0565 FU King Abdulaziz University, Jeddah, Saudi Arabia; Universiti Sains Malaysia, Kelantan, Malaysia; Intramural Research Program of National Institute on Aging, National Institutes of Health, USA FX GM, FA, MAZ, HC and MAK are supported by the King Abdulaziz University, Jeddah, Saudi Arabia. MMS is supported by the Universiti Sains Malaysia, Kelantan, Malaysia. NHG and IAT are supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, USA. NR 84 TC 4 Z9 4 U1 6 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4064 EI 1875-6638 J9 MED CHEM JI Med. Chem. PY 2016 VL 12 IS 3 BP 217 EP 225 DI 10.2174/1573406411666151030112140 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA DI7ML UT WOS:000373684700004 PM 26527155 ER PT J AU Srivastava, AK Yolcu, ES Dinc, G Sharma, RK Shirwan, H AF Srivastava, Abhishek K. Yolcu, Esma S. Dinc, Gunes Sharma, Rajesh K. Shirwan, Haval TI SA-4-1BBL/MPL as a novel immune adjuvant platform to combat cancer SO ONCOIMMUNOLOGY LA English DT Editorial Material DE Adjuvant systems; cancer vaccines; CD137; lung cancer; MPL; SA-4-1BBL; TLR ID REGULATORY T-CELLS; 4-1BB LIGAND; VACCINES AB Practical experience with cancer vaccines combined with accumulated knowledge of the complex interactions between cancer and immune system rationalize the combinatorial use of immune adjuvants for better efficacy. We recently described a novel adjuvant system based on the costimulatory SA-4-1BBL and TLR4 agonist MPL that has desired therapeutic and safety profiles. C1 [Srivastava, Abhishek K.; Yolcu, Esma S.; Dinc, Gunes; Sharma, Rajesh K.; Shirwan, Haval] Univ Louisville, Dept Microbiol & Immunol, Inst Cellular Therapeut, Louisville, KY 40292 USA. [Shirwan, Haval] Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. [Srivastava, Abhishek K.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Dinc, Gunes] Ahi Evran Univ, Sch Med, Dept Med Biyol, Kirsehir, Turkey. RP Shirwan, H (reprint author), Univ Louisville, Dept Microbiol & Immunol, Inst Cellular Therapeut, Louisville, KY 40292 USA.; Shirwan, H (reprint author), Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. EM haval.shirwan@louisville.edu RI Srivastava, Abhishek/M-7577-2014 NR 10 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 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 1 AR e1064580 DI 10.1080/2162402X.2015.1064580 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA DI3FJ UT WOS:000373383600041 ER PT J AU Zhang, L Wang, HY Yang, TS Su, ZF Fang, D Wang, YF Fang, JZ Hou, XW Le, YY Chen, KQ Wang, JM Su, SB Lin, Q Zhou, Q AF Zhang, Liang Wang, Huanyu Yang, Tianshu Su, Zhifeng Fang, Dan Wang, Yafeng Fang, Jiazhu Hou, Xinwei Le, Yingying Chen, Keqiang Wang, Ji Ming Su, Shao Bo Lin, Qing Zhou, Qi TI Formylpeptide receptor 1 mediates the tumorigenicity of human hepatocellular carcinoma cells SO ONCOIMMUNOLOGY LA English DT Article DE Cancer; GPCR; HepG2; IL-8; liver ID FORMYL-PEPTIDE RECEPTORS; HUMAN GLIOBLASTOMA CELLS; CHRONIC HEPATITIS-C; INTERLEUKIN-8 PRODUCTION; LIVER-DISEASE; GROWTH-FACTOR; TUMOR-GROWTH; KAPPA-B; ACTIVATION; CANCER AB G protein-coupled chemoattractant receptors (GPCRs) have been implicated in cancer progression. Formylpeptide receptor 1 (FPR1) was originally identified as a GPCR mediating anti-microbial host defense. However, the role of FPR1 in tumorigenesis remains poorly understood. The current study aims to investigate the potential of FPR1 to regulate human hepatoma growth and invasion. We found the FPR1 gene and protein expression in human intratumoral and peritumoral tissues of hepatocellular carcinoma (HCC) specimens and in human hepatoma cell lines. FPR1 activation mediated the migration, calcium mobilization and ERK-dependent IL-8 production by hepatic cancer cells. FPR1 knockdown substantially reduced the tumorigenicity of hepatoma cells in nude mice. Necrotic hepatic tumor cells released factor(s) that activated FPR1 in live tumor cells. Our results indicate a critical role of FPR1 in the progression of malignant human hepatic cancer. FPR1 thus may represent a molecular target for the development of novel anti-hepatoma therapeutics. C1 [Zhang, Liang] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Dept Image Guided Therapy,Canc Ctr, Guangzhou 510275, Guangdong, Peoples R China. [Wang, Huanyu; Wang, Yafeng; Zhou, Qi] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Guangzhou 510275, Guangdong, Peoples R China. [Yang, Tianshu; Fang, Dan; Fang, Jiazhu; Su, Shao Bo; Lin, Qing] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Shanghai 200092, Peoples R China. [Su, Zhifeng] S China Univ Technol, Sch Mat & Engn, Guangzhou 510641, Guangdong, Peoples R China. [Hou, Xinwei; Le, Yingying] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China. [Chen, Keqiang; Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA. [Lin, Qing] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. RP Zhou, Q (reprint author), Sun Yat Sen Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Guangzhou 510275, Guangdong, Peoples R China.; Lin, Q (reprint author), Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Shanghai 200092, Peoples R China.; Lin, Q (reprint author), Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. EM qlin2@jhmi.edu; zhouqi@mail.sysu.edu.cn FU National Nature Science Foundation of China [81200674, 31170861]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the NCI, NIH, United States of America FX This work is supported by the grants from National Nature Science Foundation of China 81200674 (Q.L) and 31170861 (S.B.S). Chen K and JM Wang were funded in part by Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E and were supported in part by the Intramural Research Program of the NCI, NIH, United States of America. NR 50 TC 0 Z9 0 U1 3 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 2 AR e1078055 DI 10.1080/2162402X.2015.1078055 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA DI3FW UT WOS:000373385000013 ER PT J AU Dauter, Z Wlodawer, A AF Dauter, Zbigniew Wlodawer, Alexander TI Progress in Protein Crystallography SO PROTEIN AND PEPTIDE LETTERS LA English DT Article DE Automation; macromolecular crystallography; protein crystallography ID ELECTRON-DENSITY MAPS; X-RAY-DIFFRACTION; MACROMOLECULAR STRUCTURE DETERMINATION; 3-DIMENSIONAL FOURIER SYNTHESIS; MOLECULAR-REPLACEMENT; SYNCHROTRON-RADIATION; ANOMALOUS SCATTERING; REFINEMENT PROCEDURE; CRYSTAL-STRUCTURES; RIBOSOMAL-SUBUNIT AB Macromolecular crystallography evolved enormously from the pioneering days, when structures were solved by "wizards" performing all complicated procedures almost by hand. In the current situation crystal structures of large systems can be often solved very effectively by various powerful automatic programs in days or hours, or even minutes. Such progress is to a large extent coupled to the advances in many other fields, such as genetic engineering, computer technology, availability of synchrotron beam lines and many other techniques, creating the highly interdisciplinary science of macromolecular crystallography. Due to this unprecedented success crystallography is often treated as one of the analytical methods and practiced by researchers interested in structures of macromolecules, but not highly competent in the procedures involved in the process of structure determination. One should therefore take into account that the contemporary, highly automatic systems can produce results almost without human intervention, but the resulting structures must be carefully checked and validated before their release into the public domain. C1 NCI, Ctr Macromol Crystallog, Frederick, MD 21701 USA. [Dauter, Zbigniew] NCI, Ctr Macromol Crystallog, Argonne, IL USA. RP Dauter, Z (reprint author), NCI, Ctr Macromol Crystallog, Argonne, IL USA. EM dauter@anl.gov; wlodawer@nih.gov FU Intramural Research Program of the National Cancer Institute, Center for Cancer Research FX Work of the authors was supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research. NR 142 TC 1 Z9 1 U1 3 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8665 EI 1875-5305 J9 PROTEIN PEPTIDE LETT JI Protein Pept. Lett. PY 2016 VL 23 IS 3 BP 201 EP 210 DI 10.2174/0929866523666160106153524 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DI7XA UT WOS:000373714100002 PM 26732246 ER PT J AU Wankhade, UD Shen, M Kolhe, R Fulzele, S AF Wankhade, Umesh D. Shen, Michael Kolhe, Ravindra Fulzele, Sadanand TI Advances in Adipose-Derived Stem Cells Isolation, Characterization, and Application in Regenerative Tissue Engineering SO STEM CELLS INTERNATIONAL LA English DT Review ID ISOLATED FAT CELLS; STRESS URINARY-INCONTINENCE; PERFRINGENS ALPHA TOXIN; IN-VIVO; LIPOLYTIC HORMONES; STROMAL CELLS; CALVARIAL DEFECTS; CONTROLLED TRIAL; CLINICAL-TRIAL; OBESE SUBJECTS AB Obesity is a complex, multifactorial disease that has been extensively researched in recent times. Obesity is characterized by excess deposition of adipose tissue in response to surplus energy. Despite the negative connotations of adipose tissue (AT), it serves as a critical endocrine organ. Adipose tissue is a source of several adipokines and cytokines which have been deemed important for both normal metabolic function and disease formation. The discoveries of metabolically active brown AT in adult humans and adipose tissue derived stem cells (ADSC) have been key findings in the past decade with potential therapeutic implications. ADSCs represent an enticing pool of multipotent adult stem cells because of their noncontroversial nature, relative abundance, ease of isolation, and expandability. A decade and a half since the discovery of ADSCs, the scientific community is still working to uncover their therapeutic potential in a wide range of diseases. In this review, we provide an overview of the recent developments in the field of ADSCs and examine their potential use in transplantation and cell-based therapies for the regeneration of diseased organs and systems. We also hope to provide perspective on how to best utilize this readily available, powerful pool of stem cells in the future. C1 [Wankhade, Umesh D.] Natl Inst Diabet Digest & Kidney Dis, NIH, Bethesda, MD 20814 USA. [Shen, Michael] Duke Univ, Durham, NC 27710 USA. [Kolhe, Ravindra] Georgia Regents Univ, Dept Pathol, Augusta, GA 30912 USA. [Fulzele, Sadanand] Georgia Regents Univ, Dept Orthoped, Augusta, GA 30912 USA. RP Fulzele, S (reprint author), Georgia Regents Univ, Dept Orthoped, Augusta, GA 30912 USA. EM sfulzele@gru.edu NR 81 TC 8 Z9 8 U1 11 U2 14 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-966X EI 1687-9678 J9 STEM CELLS INT JI Stem Cells Int. PY 2016 AR 3206807 DI 10.1155/2016/3206807 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA DI4WW UT WOS:000373501100001 ER PT J AU Kuczmarski, MF Beydoun, MA Cotugna, N Daniels, L Mason, MA Zonderman, AB Evans, MK AF Kuczmarski, Marie Fanelli Beydoun, May A. Cotugna, Nancy Daniels, Loran Mason, Marc A. Zonderman, Alan B. Evans, Michele K. TI Literacy Contributes to Greater Higher Diet Quality in a Socioeconomically Diverse Urban Prospective Cohort SO TOPICS IN CLINICAL NUTRITION LA English DT Article DE African Americans; diet; diet quality; education; literacy ID MULTIPLE-PASS METHOD; LOWER MISSISSIPPI DELTA; HEALTH LITERACY; LIMITED LITERACY; INCREASED RISK; ADULTS; NUTRITION; EDUCATION; RACE; COMMUNICATION AB Literacy influences dietary outcomes, such as food label comprehension and portion size estimation skills. This study evaluated the relationship of literacy and diet quality among Healthy Aging in Neighborhoods of Diversity across the Life Span study participants. Healthy Aging in Neighborhoods of Diversity across the Life Span is a prospective study of socioeconomically diverse urban African Americans and whites. Diet quality was measured by the Healthy Eating Index-2010 on the basis of 2 recalls, and literacy, the Wide Range Achievement Test-3rd edition reading scores. An independent and synergistic association of literacy and education with diet quality was found, emphasizing the need to consider both variables when counseling clients about nutrition. C1 [Kuczmarski, Marie Fanelli; Cotugna, Nancy] Univ Delaware, Dept Behav Hlth & Nutr, 315 McDowell Hall, Newark, DE 19716 USA. [Beydoun, May A.; Mason, Marc A.; Zonderman, Alan B.; Evans, Michele K.] NIA, Lab Epidemiol & Populat Sci, Baltimore, MD 21224 USA. [Daniels, Loran] Monell Chem Senses Ctr, 3500 Market St, Philadelphia, PA 19104 USA. RP Kuczmarski, MF (reprint author), Univ Delaware, Dept Behav Hlth & Nutr, 315 McDowell Hall, Newark, DE 19716 USA. EM mfk@udel.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural Research Program, National Institute on Aging, National Institutes of Health [Z01-AG000194] FX This work is supported by the Intramural Research Program, National Institute on Aging, National Institutes of Health (Z01-AG000194). NR 54 TC 0 Z9 0 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0883-5691 EI 1550-5146 J9 TOP CLIN NUTR JI Top. Clin. Nutr. PD JAN-MAR PY 2016 VL 31 IS 1 BP 47 EP 58 DI 10.1097/TIN.0000000000000057 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DI2BI UT WOS:000373300300005 ER PT J AU Strope, JD Price, DK Figg, WD AF Strope, Jonathan D. Price, Douglas K. Figg, William D. TI Building a hit list for the fight against metastatic castration resistant prostate cancer SO CANCER BIOLOGY & THERAPY LA English DT Article DE Actionable tumors; androgen deprivation; androgen receptor; genetic alterations; mCRPC; PTEN; translational medication ID PTEN AB Identification of genetic alterations in Metastatic Castration Resistant Prostate Cancer (mCRPC) may provide scientists and clinicians with a list of new targets for drug research and development. Recently published in Cell, Robinson et al. present the first look at genetic data from mCRPC lesions gathered over multiple years and from many institutions. C1 [Strope, Jonathan D.; Price, Douglas K.; Figg, William D.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM figgw@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 5 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PY 2016 VL 17 IS 3 BP 231 EP 232 DI 10.1080/15384047.2016.1139270 PG 2 WC Oncology SC Oncology GA DH9JI UT WOS:000373112000001 PM 26822877 ER PT J AU Renoux, C Parrow, N Faes, C Joly, P Hardeman, M Tisdale, J Levine, M Garnier, N Bertrand, Y Kebaili, K Cuzzubbo, D Cannas, G Martin, C Connes, P AF Renoux, Celine Parrow, Nermi Faes, Camille Joly, Philippe Hardeman, Max Tisdale, John Levine, Mark Garnier, Nathalie Bertrand, Yves Kebaili, Kamila Cuzzubbo, Daniela Cannas, Giovanna Martin, Cyril Connes, Philippe TI Importance of methodological standardization for the ektacytometric measures of red blood cell deformability in sickle cell anemia SO CLINICAL HEMORHEOLOGY AND MICROCIRCULATION LA English DT Article DE Ektacytometry; sickle cell disease; red blood cell deformability; standardization; clinical relevance ID ENDOTHELIAL-CELLS; DISEASE; HEMOLYSIS; QUANTIFICATION; EXPOSURE; CRISIS; ALPHA; FLOW AB Red blood cell (RBC) deformability is severely decreased in patients with sickle cell anemia (SCA), which plays a role in the pathophysiology of the disease. However, investigation of RBC deformability from SCA patients demands careful methodological considerations. We assessed RBC deformability by ektacytometry (LORRCA MaxSis, Mechatronics, The Netherlands) in 6 healthy individuals and 49 SCA patients and tested the effects of different heights of the RBC diffraction patterns, obtained by altering the camera gain of the LORRCA, on the result of RBC deformability measurements, expressed as Elongation Index (EI). Results indicate that the pattern of RBCs from control subjects adopts an elliptical shape under shear stress, whereas the pattern of RBCs from individuals with SCA adopts a diamond shape arising from the superposition of elliptical and circular patterns. The latter represent rigid RBCs. While the EI measures did not change with the variations of the RBC diffraction pattern heights in the control subjects, we observed a decrease of EI when the RBC diffraction pattern height is increased in the SCA group. The differences in SCA EI values measured at 5 Pa between the different diffraction pattern heights correlated with the percent of hemoglobin S and the percent of sickled RBC observed by microscopy. Our study confirms that the camera gain or aperture of the ektacytometer should be used to standardize the size of the RBC diffraction pattern height when measuring RBC deformability in sickle cell patients and underscores the potential clinical utility of this technique. C1 [Renoux, Celine; Faes, Camille; Joly, Philippe; Martin, Cyril; Connes, Philippe] Univ Lyon 1, Lab CRIS EA647, Team Vasc Biol & Red Blood Cell, F-69365 Lyon, France. [Renoux, Celine; Joly, Philippe] Hop Edouard Herriot, Lab Biochim & Biol Mol, Lyon, France. [Parrow, Nermi; Tisdale, John; Levine, Mark] NIH, Washington, DC USA. [Hardeman, Max] Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Garnier, Nathalie; Bertrand, Yves; Kebaili, Kamila; Cuzzubbo, Daniela] Inst Hematol & Oncol Pediat, Lyon, France. [Renoux, Celine; Faes, Camille; Joly, Philippe; Martin, Cyril; Connes, Philippe] Lab Excellence GR Ex Red Cell Genesis Death, Paris, France. [Cannas, Giovanna] Hop Edouard Herriot, Serv Med Interne, Lyon, France. [Connes, Philippe] Inst Univ France, Paris, France. RP Connes, P (reprint author), Univ Lyon 1, CRIS EA Lab 647, Team Vasc Biol & Red Blood Cell, F-69622 Villeurbanne, France. EM pconnes@yahoo.fr NR 23 TC 3 Z9 3 U1 3 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1386-0291 EI 1875-8622 J9 CLIN HEMORHEOL MICRO JI Clin. Hemorheol. Microcirc. PY 2016 VL 62 IS 2 BP 173 EP 179 DI 10.3233/CH-151979 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DH9IS UT WOS:000373110400008 PM 26444610 ER PT J AU Straughan, DM Azoury, SC Shukla, V AF Straughan, David M. Azoury, Said C. Shukla, Vivek TI Anaplastic Lymphoma Kinase Inhibitors in Non-Small Cell Lung Cancer SO CURRENT DRUG TARGETS LA English DT Article DE Anaplastic; inhibitors; kinase; lymphoma; NSCLC ID CENTRAL-NERVOUS-SYSTEM; ADVANCED SOLID TUMORS; EML4-ALK FUSION GENE; ALK INHIBITOR; TYROSINE KINASE; OPEN-LABEL; NPM-ALK; CRIZOTINIB; MUTATIONS; HSP90 AB Lung cancer is the leading cause of cancer death among both sexes in the United States and non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Over the last several decades, there have been many advances in both surgical approaches and systemic therapies for the treatment of NSCLC, but the prognosis for advanced disease remains poor. New research, however, is exploring the use of targeted therapies for the treatment of NSCLC. The anaplastic lymphoma kinase (ALK) is involved in normal mammalian central nervous system development. A novel fusion gene involving ALK and the echinoderm microtubule-associated protein-like 4 (EML4) gene has been associated with approximately 5% of NSCLCs and is mutually exclusive of other oncogenic driver mutations. Targeted therapies against this ALK rearrangement are a relatively new treatment modality that aims to improve the prognosis of patients with late-stage disease. Two such drugs have Food and Drug Administration (FDA) approval currently: Crizotinib and Ceritinib. Many other ALK inhibitors are currently being studied in clinical trials as well. The authors aim to provide a comprehensive review of ALK inhibitors for use in NSCLC as well as the future directions and challenges to developing these targeted therapies. C1 [Straughan, David M.] Univ S Florida, Dept Surg, Morsani Coll Med, Tampa, FL 33620 USA. [Azoury, Said C.] Johns Hopkins Univ Hosp, Dept Surg, Baltimore, MD 21287 USA. [Shukla, Vivek] NCI, Thorac & GI Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Shukla, V (reprint author), NIH, Thorac & GI Oncol Branch, Bethesda, MD 20892 USA. EM vivek.shukla@nih.gov NR 64 TC 0 Z9 0 U1 1 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 EI 1873-5592 J9 CURR DRUG TARGETS JI Curr. Drug Targets PY 2016 VL 17 IS 6 BP 739 EP 745 DI 10.2174/1573399811666150615144336 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DH9NV UT WOS:000373123800012 PM 26073862 ER PT J AU Waheed, AA Tachedjian, G AF Waheed, Abdul A. Tachedjian, Gilda TI Current and Emerging Drug Targets for Human Immunodeficiency Virus SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Editorial Material ID HIV-1 REVERSE-TRANSCRIPTASE; INHIBITORS C1 [Waheed, Abdul A.] NCI, Virus Cell Interact Sect, HIV DRP, NIH, Frederick, MD 21702 USA. [Tachedjian, Gilda] Burnet Inst, Ctr Biomed Res, 85 Commercial Rd, Melbourne, Vic 3004, Australia. RP Waheed, AA (reprint author), NCI, Virus Cell Interact Sect, HIV DRP, NIH, Frederick, MD 21702 USA.; Tachedjian, G (reprint author), Burnet Inst, Ctr Biomed Res, 85 Commercial Rd, Melbourne, Vic 3004, Australia. EM waheedab@mail.nih.gov; gildat@burnet.edu.au NR 10 TC 0 Z9 0 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-5294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2016 VL 16 IS 10 BP 1072 EP 1073 DI 10.2174/1568026616999150918145541 PG 2 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA DH4XW UT WOS:000372790000002 PM 26381413 ER PT J AU Waheed, AA Tachedjian, G AF Waheed, Abdul A. Tachedjian, Gilda TI Why Do We Need New Drug Classes for HIV Treatment and Prevention? SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE Antiretroviral therapy; Drug discovery; Drug resistance; HIV; Host cell factors; Pre-exposure prophylaxis ID TREATMENT-NAIVE INDIVIDUALS; RANDOMIZED CONTROLLED-TRIAL; RESOURCE-LIMITED SETTINGS; PREEXPOSURE PROPHYLAXIS; DOUBLE-BLIND; ANTIRETROVIRAL THERAPY; REVERSE-TRANSCRIPTASE; VAGINAL GEL; IMMUNODEFICIENCY-VIRUS; RESISTANCE MUTATIONS AB The biomedical intervention that has had a major impact on the natural history of HIV and on the global HIV epidemic is antiretroviral therapy (ART). However, the emergence of drug-resistant HIV, an inevitable consequence of increasing use of antiretroviral drugs, poses a major threat to ART success. At the turn of this century, access to life-saving ART was accelerated in low and middle-income countries with the Millennium Development Goal of 15 million individuals receiving ART by 2015 expected to be achieved. However, ART access needs to continue to expand to help bring HIV under control by 2030. The standard of care for people living with HIV in resource- limited settings differs dramatically compared to high-income countries, and not unexpectedly, ART rollout in these settings has resulted in an increase in acquired and transmitted drug resistance. Also of concern, the same drug classes used for ART have been approved or are being progressed for HIV prevention and drug resistance could mitigate their effectiveness for treatment and prevention. In the absence of an effective HIV vaccine and cure, it is imperative that the antiretroviral drug pipeline contains new classes of HIV inhibitors that are active against circulating drug-resistant strains. Studies to advance our fundamental understanding of HIV replication needs to continue, including the interplay between virus and host cell factors, to identify and characterize new drug targets for chemotherapeutic intervention. C1 [Waheed, Abdul A.] Natl Canc Inst Frederick, Virus Cell Interact Sect, HIV Dynam & Replicat Program, NIH, Frederick, MD 21702 USA. [Tachedjian, Gilda] Burnet Inst, Ctr Biomed Res, Melbourne, Vic 3004, Australia. [Tachedjian, Gilda] Monash Univ, Dept Microbiol, Clayton, Vic 3168, Australia. [Tachedjian, Gilda] Monash Univ, Dept Infect Dis, Melbourne, Vic 3004, Australia. [Tachedjian, Gilda] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia. RP Tachedjian, G (reprint author), Burnet Inst, Ctr Biomed Res, Retroviral Biol & Antivirals Lab, GPO Box 2284, Melbourne, Vic, Australia. EM gildat@burnet.edu.au FU National Health and Medical Research Council (NHMRC) of Australia [APP1064900, APP1088564] FX The authors declare no conflict of interest. G.T. was supported by the National Health and Medical Research Council (NHMRC) of Australia (Project Grants APP1064900 and APP1088564). NR 73 TC 2 Z9 2 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-5294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2016 VL 16 IS 12 BP 1343 EP 1349 DI 10.2174/1568026616999151013124606 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA DH5RB UT WOS:000372848400001 PM 26459806 ER PT J AU Villalba, K Devieux, JG Rosenberg, R Cadet, JL AF Villalba, Karina Devieux, Jessy G. Rosenberg, Rhonda Cadet, Jean Lud TI Serotonin-Related Gene Polymorphisms and Asymptomatic Neurocognitive Impairment in HIV-Infected Alcohol Abusers SO GENETICS RESEARCH INTERNATIONAL LA English DT Article ID VERBAL-LEARNING TEST; IMMUNODEFICIENCY-VIRUS-INFECTION; TRYPTOPHAN HYDROXYLASE-2 GENE; TRANSPORTER GENE; WORKING-MEMORY; TRANSMISSION DISEQUILIBRIUM; EXECUTIVE FUNCTIONS; CLINICAL-FEATURES; PREFRONTAL CORTEX; PROMOTER REGION AB HIV-infected individuals continue to experience neurocognitive deterioration despite virologically successful treatments. While the cause remains unclear, evidence suggests that HIV-associated neurocognitive disorders (HAND) may be associated with neurobehavioral dysfunction. Genetic variants have been explored to identify risk markers to determine neuropathogenesis of neurocognitive deterioration. Memory deficits and executive dysfunction are highly prevalent among HIV-infected adults. These conditions can affect their quality of life and HIV risk-taking behaviors. Single nucleotide polymorphisms in the SLC6A4, TPH2, and GALM genes may affect the activity of serotonin and increase the risk of HAND. The present study explored the relationship between SLC6A4, TPH2, and GALM genes and neurocognitive impairment in HIV-infected alcohol abusers. A total of 267 individuals were genotyped for polymorphisms in SLC6A4 5-HTTLPR, TPH2 rs4570625, and GALM rs6741892. To assess neurocognitive functions, the Short Category and the Auditory Verbal Learning Tests were used. TPH2 SNP rs4570625 showed a significant association with executive function in African American males (odds ratio 4.8, 95% CI, 1.5-14.8; P = 0.005). Similarly, GALM SNP rs6741892 showed an increased risk with African American males (odds ratio 2.4, 95% CI, 1.2-4.9; P = 0.02). This study suggests that TPH2 rs4570625 and GALM rs6741892 polymorphisms may be risk factors for HAND. C1 [Villalba, Karina; Devieux, Jessy G.; Rosenberg, Rhonda] Florida Int Univ, Robert Stempel Coll Publ Hlth & Social Work, Dept Hlth Promot & Dis Prevent, Miami, FL 33181 USA. [Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, DHHS, NIH,Intramural Res Program, Baltimore, MD USA. RP Villalba, K (reprint author), Florida Int Univ, Robert Stempel Coll Publ Hlth & Social Work, Dept Hlth Promot & Dis Prevent, Miami, FL 33181 USA. EM kvill012@fiu.edu NR 56 TC 0 Z9 0 U1 7 U2 7 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-3154 EI 2090-3162 J9 GENET RES INT JI Genet. Res. Int. PY 2016 AR 7169172 DI 10.1155/2016/7169172 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DH7XU UT WOS:000373008200001 ER PT J AU Mishra, B Swaroop, A Kandpal, RP AF Mishra, Bibhudatta Swaroop, Anand Kandpal, Raj P. TI Genetic components in diabetic retinopathy SO INDIAN JOURNAL OF OPHTHALMOLOGY LA English DT Article DE Diabetic complications; genetic association; multifactorial disease; retinal disorders; susceptibility variants ID ENDOTHELIAL GROWTH-FACTOR; GENOME-WIDE ASSOCIATION; GLYCOSYLATION END-PRODUCTS; ALDOSE REDUCTASE-ACTIVITY; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; SUSCEPTIBILITY GENES; ALBUMIN EXCRETION; IDENTICAL-TWINS; COMPLICATIONS AB Diabetic retinopathy (DR) is a serious complication of diabetes, which is fast reaching epidemic proportions worldwide. While tight glycemic control remains the standard of care for preventing the progression of DR, better insights into DR etiology require understanding its genetic basis, which in turn may assist in the design of novel treatments. During the last decade, genomic medicine is increasingly being applied to common multifactorial diseases such as diabetes and age-related macular degeneration. The contribution of genetics to the initiation and progression of DR has been recognized for some time, but the involvement of specific genes and genetic variants remains elusive. Several investigations are currently underway for identifying DR susceptibility loci through linkage studies, candidate gene approaches, and genome-wide association studies. Advent of next generation sequencing and high throughput genomic technologies, development of novel bioinformatics tools and collaborations among research teams should facilitate such investigations. Here, we review the current state of genetic studies in DR and discuss reported findings in the context of biochemical, cell biological and therapeutic advances. We propose the development of a consortium in India for genetic studies with large cohorts of patients and controls from limited geographical areas to stratify the impact of the environment. Uniform guidelines should be established for clinical phenotyping and data collection. These studies would permit identification of genetic loci for DR susceptibility in the Indian population and should be valuable for better diagnosis and prognosis, and for clinical management of this blinding disease. C1 [Mishra, Bibhudatta; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. [Kandpal, Raj P.] Western Univ Hlth Sci, Dept Basic Med Sci, Pomona, CA USA. [Kandpal, Raj P.] Western Univ Hlth Sci, Western Diabet Inst, Pomona, CA USA. RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. EM swaroopa@nei.nih.gov OI Swaroop, Anand/0000-0002-1975-1141 FU Intramural Research Program of the National Eye Institute [EY000546] FX Our research is supported by Intramural Research Program of the National Eye Institute (EY000546). NR 67 TC 2 Z9 2 U1 2 U2 2 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0301-4738 EI 1998-3689 J9 INDIAN J OPHTHALMOL JI Indian J. Ophthalmol. PD JAN PY 2016 VL 64 IS 1 BP 55 EP 61 DI 10.4103/0301-4738.178153 PG 7 WC Ophthalmology SC Ophthalmology GA DH7ID UT WOS:000372965700010 PM 26953025 ER PT J AU Liu, YH Kheradmand, F Davis, CF Scheurer, ME Wheeler, D Tsavachidis, S Armstrong, G Simpson, C Mandal, D Kupert, E Anderson, M You, M Xiong, DH Pikielny, C Schwartz, AG Bailey-Wilson, J Gaba, C De Andrade, M Yang, P Pinney, SM Amos, CI Spitz, MR AF Liu, Yanhong Kheradmand, Farrah Davis, Caleb F. Scheurer, Michael E. Wheeler, David Tsavachidis, Spiridon Armstrong, Georgina Simpson, Claire Mandal, Diptasri Kupert, Elena Anderson, Marshall You, Ming Xiong, Donghai Pikielny, Claudio Schwartz, Ann G. Bailey-Wilson, Joan Gaba, Colette De Andrade, Mariza Yang, Ping Pinney, Susan M. Amos, Christopher I. Spitz, Margaret R. CA Genetic Epidemiology Lung Cancer TI Focused Analysis of Exome Sequencing Data for Rare Germline Mutations in Familial and Sporadic Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Exome sequencing; Single-nucleotide variants; Lung cancer; Chronic obstructive pulmonary disease; Familial; Sporadic ID GENOME-WIDE ASSOCIATION; BETA-HYDROXYLASE DBH; SMOKING-BEHAVIOR; GENETIC-VARIANTS; OVARIAN-CANCER; RISK; PREDICTION; LOCI; VALIDATION; NIDOGEN-2 AB Introduction: The association between smoking-induced chronic obstructive pulmonary disease (COPD) and lung cancer (LC) is well documented. Recent genome-wide association studies (GWAS) have identified 28 susceptibility loci for LC, 10 for COPD, 32 for smoking behavior, and 63 for pulmonary function, totaling 107 nonoverlapping loci. Given that common variants have been found to be associated with LC in genome-wide association studies, exome sequencing of these high-priority regions has great potential to identify novel rare causal variants. Methods: To search for disease-causing rare germline mutations, we used a variation of the extreme phenotype approach to select 48 patients with sporadic LC who reported histories of heavy smoking-37 of whom also exhibited carefully documented severe COPD (in whom smoking is considered the overwhelming determinant) and 54 unique familial LC cases from families with at least three first-degree relatives with LC (who are likely enriched for genomic effects). Results: By focusing on exome profiles of the 107 target loci, we identified two key rare mutations. A heterozygous p.Arg696Cys variant in the coiled-coil domain containing 147 (CCDC147) gene at 10q25.1 was identified in one sporadic and two familial cases. The minor allele frequency (MAF) of this variant in the 1000 Genomes database is 0.0026. The p.Va126Met variant in the dopamine beta-hydroxylase (DBH) gene at 9q34.2 was identified in two sporadic cases; the minor allele frequency of this mutation is 0.0034 according to the 1000 Genomes database. We also observed three suggestive rare mutations on 15q25.1: iron -responsive element binding protein neuronal 2 (IREB2); cholinergic receptor, nicotinic, alpha 5 (neuronal) (CHRNA5); and cholinergic receptor, nicotinic, beta 4 (CHRNB4). Conclusions: Our results demonstrated highly disruptive risk -conferring CCDC147 and DBH mutations. (C) 2015 by the International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. C1 [Liu, Yanhong; Kheradmand, Farrah; Davis, Caleb F.; Scheurer, Michael E.; Wheeler, David; Tsavachidis, Spiridon; Armstrong, Georgina; Spitz, Margaret R.] Baylor Coll Med, Houston, TX 77030 USA. [Simpson, Claire] NIH, Baltimore, MD USA. [Mandal, Diptasri] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [Kupert, Elena; Pinney, Susan M.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Anderson, Marshall; You, Ming; Xiong, Donghai] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Pikielny, Claudio; Amos, Christopher I.] Dartmouth Coll, 1 Med Ctr Dr, Lebanon, NH 03756 USA. [Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Bailey-Wilson, Joan] Human Genome Res Inst, Bethesda, MD USA. [Gaba, Colette] Univ Toledo, Coll Med, 2801 W Bancroft St, Toledo, OH 43606 USA. [De Andrade, Mariza; Yang, Ping] Mayo Clin, Coll Med, Rochester, MN USA. RP Spitz, MR (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. EM spitz@bcm.edu FU Intramural NIH HHS; NCI NIH HHS [P30 CA023108, K07 CA181480, K07CA181480, P30 CA022453, P30 CA125123, P30CA022453, P30CA023108, P30CA125123, R01 CA060691, R01 CA080127, R01 CA084354, R01 CA087895, R01 CA127219, R01 CA134433, R01 CA134682, R01 CA80127, R01 CA84354, R01 CA87895, R01CA134682, R03 CA077118, R03 CA77118, U01 CA076293, U01CA076293, U19 CA148127, U19CA148127]; NHGRI NIH HHS [N01HG65404]; NHLBI NIH HHS [HHSN268201200007C, R01 HL082487, R01 HL110883]; NIEHS NIH HHS [P30 ES006096, P30-ES006096]; NIGMS NIH HHS [P20 GM103534, P20GM103534]; NLM NIH HHS [T15 LM007093, T15LM007093]; PHS HHS [HHSN268201 200007C] NR 39 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JAN PY 2016 VL 11 IS 1 BP 52 EP 61 DI 10.1016/j.jtho.2015.09.015 PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DH9CO UT WOS:000373094200006 PM 26762739 ER PT J AU Sousa, AA Hassan, SA Knittel, LL Balbo, A Aronova, MA Brown, PH Schuckc, P Leapman, RD AF Sousa, Alioscka A. Hassan, Sergio A. Knittel, Luiza L. Balbo, Andrea Aronova, Maria A. Brown, Patrick H. Schuckc, Peter Leapman, Richard D. TI Biointeractions of ultrasmall glutathione-coated gold nanoparticles: effect of small size variations SO NANOSCALE LA English DT Article ID SIDE-CHAIN INTERACTIONS; ANALYTICAL ULTRACENTRIFUGATION; RENAL CLEARANCE; IN-VIVO; DEPENDENT MANNER; BIODISTRIBUTION; NANOCLUSTERS; TOXICITY; PLASMA; CORONA AB Recent in vivo studies have established ultrasmall (<3 nm) gold nanoparticles coated with glutathione (AuGSH) as a promising platform for applications in nanomedicine. However, systematic in vitro investigations to gain a more fundamental understanding of the particles' biointeractions are still lacking. Herein we examined the behavior of ultrasmall AuGSH in vitro, focusing on their ability to resist aggregation and adsorption from serum proteins. Despite having net negative charge, AuGSH particles were colloidally stable in biological media and able to resist binding from serum proteins, in agreement with the favorable bioresponses reported for AuGSH in vivo. However, our results revealed disparate behaviors depending on nanoparticle size: particles between 2 and 3 nm in core diameter were found to readily aggregate in biological media, whereas those strictly under 2 nm were exceptionally stable. Molecular dynamics simulations provided microscopic insight into interparticle interactions leading to aggregation and their sensitivity to the solution composition and particle size. These results have important implications, in that seemingly small variations in size can impact the biointeractions of ultrasmall AuGSH, and potentially of other ultrasmall nanoparticles as well. C1 [Sousa, Alioscka A.; Knittel, Luiza L.] Univ Fed Sao Paulo, Dept Biochem, Sao Paulo, SP, Brazil. [Hassan, Sergio A.] NIH, DCB CIT, Ctr Mol Modeling, Bldg 10, Bethesda, MD 20892 USA. [Balbo, Andrea; Aronova, Maria A.; Brown, Patrick H.; Schuckc, Peter; Leapman, Richard D.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. RP Sousa, AA (reprint author), Univ Fed Sao Paulo, Dept Biochem, Sao Paulo, SP, Brazil.; Leapman, RD (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. EM alioscka.sousa@unifesp.br; leapmanr@mail.nih.gov FU Sao Paulo Research Foundation, Sao Paulo, Brazil [FAPESP: 2013/18481-5]; Brazilian National Council for Scientific and Technological Development [CNPq: 476784/2013-1]; National Institute of Biomedical Imaging and Bioengineering; Center for Information Technology, National Institutes of Health, Bethesda, U.S.A. FX We would like to acknowledge Prof. M. L. V. Oliva for providing access to instrumentation. We acknowledge the Spectroscopy and Calorimetry facility at Brazilian Biosciences National Laboratory (LNBio), CNPEM, Campinas, Brazil, for their support with the analytical ultracentrifuge. This study utilized the high-performance computer capabilities of the Biowulf PC/Linux cluster at the NIH. This work was supported by the Sao Paulo Research Foundation (FAPESP: 2013/18481-5), Sao Paulo, Brazil, by the Brazilian National Council for Scientific and Technological Development (CNPq: 476784/2013-1), and by the Intramural Research Programs of the National Institute of Biomedical Imaging and Bioengineering and the Center for Information Technology, National Institutes of Health, Bethesda, U.S.A. NR 62 TC 3 Z9 3 U1 15 U2 31 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2016 VL 8 IS 12 BP 6577 EP 6588 DI 10.1039/c5nr07642k PG 12 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA DH5SG UT WOS:000372851500043 PM 26934984 ER PT J AU Zhu, GZ Liu, YJ Yang, XY Kim, YH Zhang, HM Jia, R Liao, HS Jin, A Lin, J Aronova, M Leapman, R Nie, ZH Niu, G Chen, XY AF Zhu, Guizhi Liu, Yijing Yang, Xiangyu Kim, Young-Hwa Zhang, Huimin Jia, Rui Liao, Hsien-Shun Jin, Albert Lin, Jing Aronova, Maria Leapman, Richard Nie, Zhihong Niu, Gang Chen, Xiaoyuan TI DNA-inorganic hybrid nanovaccine for cancer immunotherapy SO NANOSCALE LA English DT Article ID CPG DNA; DENDRITIC CELLS; BIOMEDICAL APPLICATIONS; SYNTHETIC VACCINES; DELIVERY; OLIGONUCLEOTIDES; SIGNALS; NANOFLOWERS; ACTIVATION; PARTICLES AB Cancer evolves to evade or compromise the surveillance of the immune system, and cancer immunotherapy aims to harness the immune system in order to inhibit cancer development. Unmethylated CpG dinucleotide-containing oligonucleotides (CpG), a class of potent adjuvants that activate the toll-like receptor 9 (TLR9) located in the endolysosome of many antigen-presenting cells (APCs), are promising for cancer immunotherapy. However, clinical application of synthetic CpG confronts many challenges such as suboptimal delivery into APCs, unfavorable pharmacokinetics caused by limited biostability and short in vivo half-life, and side effects associated with leaking of CpG into the systemic circulation. Here we present DNA-inorganic hybrid nanovaccines (hNVs) for efficient uptake into APCs, prolonged tumor retention, and potent immunostimulation and cancer immunotherapy. hNVs were self-assembled from concatemer CpG analogs and magnesium pyrophosphate (Mg(2)PPi). Mg(2)PPi renders hNVs resistant to nuclease degradation and thermal denaturation, both of which are demanding characteristics for effective vaccination and the storage and transportation of vaccines. Fluorophore-labeled hNVs were tracked to be efficiently internalized into the endolysosomes of APCs, where Mg(2)PPi was dissolved in an acidic environment and thus CpG analogs were exposed to hNVs. Internalized hNVs in APCs led to (1) elevated secretion of proinflammatory factors, and (2) elevated expression of co-stimulatory factors. Compared with molecular CpG, hNVs dramatically prolonged the tissue retention of CpG analogs and reduced splenomegaly, a common side effect of CpG. In a melanoma mouse model, two injections of hNVs significantly inhibited the tumor growth and outperformed the molecular CpG. These results suggest hNVs are promising for cancer immunotherapy. C1 [Zhu, Guizhi; Liu, Yijing; Yang, Xiangyu; Kim, Young-Hwa; Zhang, Huimin; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Jia, Rui] NICHHD, Sect Intracellular Prot Trafficking, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. [Liao, Hsien-Shun; Jin, Albert; Lin, Jing; Aronova, Maria; Leapman, Richard] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. [Nie, Zhihong] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This work was supported by the intramural research program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 37 TC 3 Z9 3 U1 15 U2 36 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2016 VL 8 IS 12 BP 6684 EP 6692 DI 10.1039/c5nr08821f PG 9 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA DH5SG UT WOS:000372851500054 PM 26947116 ER PT J AU Plow, EB Sankarasubramanian, V Cunningham, DA Potter-Baker, K Varnerin, N Cohen, LG Sterr, A Conforto, AB Machado, AG AF Plow, E. B. Sankarasubramanian, V. Cunningham, D. A. Potter-Baker, K. Varnerin, N. Cohen, L. G. Sterr, A. Conforto, A. B. Machado, A. G. TI Models to Tailor Brain Stimulation Therapies in Stroke SO NEURAL PLASTICITY LA English DT Review ID TRANSCRANIAL MAGNETIC STIMULATION; PRIMARY MOTOR CORTEX; CROSSED CEREBELLAR DIASCHISIS; THETA-BURST STIMULATION; CORTICOSPINAL SYSTEM INTEGRITY; INVASIVE CORTICAL STIMULATION; PRIMATE RETICULOSPINAL TRACT; POSITRON-EMISSION-TOMOGRAPHY; INDUCED MOVEMENT THERAPY; ADULT SQUIRREL-MONKEYS AB A great challenge facing stroke rehabilitation is the lack of information on how to derive targeted therapies. As such, techniques once considered promising, such as brain stimulation, have demonstrated mixed efficacy across heterogeneous samples in clinical studies. Here, we explain reasons, citing its one-type-suits-all approach as the primary cause of variable efficacy. We present evidence supporting the role of alternate substrates, which can be targeted instead in patients with greater damage and deficit. Building on this groundwork, this review will also discuss different frameworks on how to tailor brain stimulation therapies. To the best of our knowledge, our report is the first instance that enumerates and compares across theoretical models from upper limb recovery and conditions like aphasia and depression. Here, we explain how different models capture heterogeneity across patients and how they can be used to predict which patients would best respond to what treatments to develop targeted, individualized brain stimulation therapies. Our intent is to weigh pros and cons of testing each type of model so brain stimulation is successfully tailored to maximize upper limb recovery in stroke. C1 [Plow, E. B.; Sankarasubramanian, V.; Cunningham, D. A.; Potter-Baker, K.; Varnerin, N.] Cleveland Clin Fdn, Lerner Res Inst, Dept Biomed Engn, Cleveland, OH 44195 USA. [Cunningham, D. A.] Kent State Univ, Sch Biomed Sci, Kent, OH 44242 USA. [Cohen, L. G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sec, NIH, Bethesda, MD 20892 USA. [Sterr, A.] Univ Surrey, Guildford GU2 7XH, Surrey, England. [Conforto, A. B.] Univ Sao Paulo, Hosp Clin, Dept Neurol, Neurol Clin Div, BR-05508090 Sao Paulo, SP, Brazil. [Conforto, A. B.] Hosp Israelita Albert Einstein, BR-05652900 Sao Paulo, SP, Brazil. [Machado, A. G.] Cleveland Clin Fdn, Cleveland Clin, Neurol Inst, Ctr Neurol Restorat,Neurosurg, Cleveland, OH 44195 USA. RP Plow, EB (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Biomed Engn, Cleveland, OH 44195 USA. EM plowe2@ccf.org FU National Institutes of Health [1K01HD069504]; American Heart Association [13BGIA17120055, 16GRNT27720019]; Clinical and Translational Science Collaborative [RPC2014-1067]; NIH [5R01NS07634, 5R01HD061363] FX Support for this work comes from grants from the National Institutes of Health (1K01HD069504) and American Heart Association's Grants 13BGIA17120055 and 16GRNT27720019 awarded to E. B. Plow, Clinical and Translational Science Collaborative (RPC2014-1067) to D. A. Cunningham, NIH 5R01NS07634 to A. B. Conforto, and 5R01HD061363 to A. G. Machado. NR 158 TC 1 Z9 1 U1 3 U2 6 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2016 AR 4071620 DI 10.1155/2016/4071620 PG 17 WC Neurosciences SC Neurosciences & Neurology GA DH7TD UT WOS:000372995800001 ER PT J AU Sweeney, EM Shinohara, RT Dewey, BE Schindler, MK Muschelli, J Reich, DS Crainiceanu, CM Eloyan, A AF Sweeney, Elizabeth M. Shinohara, Russell T. Dewey, Blake E. Schindler, Matthew K. Muschelli, John Reich, Daniel S. Crainiceanu, Ciprian M. Eloyan, Ani TI Relating multi-sequence longitudinal intensity profiles and clinical covariates in incident multiple sclerosis lesions SO NEUROIMAGE-CLINICAL LA English DT Article DE Structural magnetic resonance imaging; Multi-sequence imaging; Longitudinal study; Multiple sclerosis; Longitudinal lesion behavior; Principal component analysis and regression; Function-on-scalar regression; Expert rater trial; Biomarker ID MRI; SEGMENTATION; DIFFUSION; REPAIR AB The formation of multiple sclerosis (MS) lesions is a complex process involving inflammation, tissue damage, and tissue repair - all of which are visible on structural magnetic resonance imaging (MRI) and potentially modifiable by pharmacological therapy. In this paper, we introduce two statistical models for relating voxel-level, longitudinal, multi-sequence structural MRI intensities within MS lesions to clinical information and therapeutic interventions: (1) a principal component analysis (PCA) and regression model and (2) function-on-scalar regression models. To do so, we first characterize the post-lesion incidence repair process on longitudinal, multi-sequence structural MRI from 34 MS patients as voxel-level intensity profiles. For the PCA regression model, we perform PCA on the intensity profiles to develop a voxel-level biomarker for identifying slow and persistent, long-term intensity changes within lesion tissue voxels. The proposed biomarker's ability to identify such effects is validated by two experienced clinicians (a neuroradiologist and a neurologist). On a scale of 1 to 4, with 4 being the highest quality, the neuroradiologist gave the score on the first PC a median quality rating of 4 (95% CI: [4,4]), and the neurologist gave the score a median rating of 3 (95% CI: [3,3]). We then relate the biomarker to the clinical information in a mixed model framework. Treatment with disease-modifying therapies (p < 0.01), steroids (p < 0.01), and being closer to the boundary of abnormal signal intensity (p < 0.01) are all associated with return of a voxel to an intensity value closer to that of normal-appearing tissue. The function-on-scalar regression model allows for assessment of the post-incidence time points at which the covariates are associated with the profiles. In the function-on-scalar regression, both age and distance to the boundary were found to have a statistically significant association with the lesion intensities at some time point. The two models presented in this article show promise for understanding the mechanisms of tissue damage in MS and for evaluating the impact of treatments for the disease in clinical trials. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Sweeney, Elizabeth M.; Muschelli, John; Reich, Daniel S.; Crainiceanu, Ciprian M.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. [Sweeney, Elizabeth M.; Dewey, Blake E.; Schindler, Matthew K.; Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, Div Neuroimmunol & Neurovirol, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Shinohara, Russell T.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Eloyan, Ani] Brown Univ, Sch Publ Hlth, Dept Biostat, Providence, RI 02912 USA. RP Sweeney, EM (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.; Sweeney, EM (reprint author), NINDS, Translat Neuroradiol Unit, Div Neuroimmunol & Neurovirol, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM emsweene@jhsph.edu RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU NIH from National Institute of Biomedical Imaging and Bioengineering [RO1 EB012547]; National Institute of Neurological Disorders and Stroke (NINDS) [RO1 NS060910, RO1 NS085211]; National Institute of Aging [T32 AG021334]; National Institute of Mental Health [RO1 MH095836]; Intramural Research Program of NINDS FX The project described is supported in part by the NIH grants RO1 EB012547 from the National Institute of Biomedical Imaging and Bioengineering, RO1 NS060910 and RO1 NS085211 from the National Institute of Neurological Disorders and Stroke (NINDS), T32 AG021334 from the National Institute of Aging, and RO1 MH095836 from the National Institute of Mental Health. The research is also supported by the Intramural Research Program of NINDS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. NR 26 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 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2016 VL 10 BP 1 EP 17 DI 10.1016/j.nicl.2015.10.013 PG 17 WC Neuroimaging SC Neurosciences & Neurology GA DI0LX UT WOS:000373189000001 PM 26693397 ER PT J AU Borstad, AL Choi, S Schmalbrock, P Nichols-Larsen, DS AF Borstad, Alexandra L. Choi, Seongjin Schmalbrock, Petra Nichols-Larsen, Deborah S. TI Frontoparietal white matter integrity predicts haptic performance in chronic stroke SO NEUROIMAGE-CLINICAL LA English DT Article DE Haptic performance; Stroke; Upper extremity; Diffusion MRI; Probabilistic tractography; Hand Active Sensation Test; Sensorimotor; Frontoparietal network ID TRANSCRANIAL MAGNETIC STIMULATION; DIFFUSION-TENSOR MRI; EVENT-RELATED FMRI; FUNCTIONAL CONNECTIVITY; TACTILE DISCRIMINATION; LENGTH DISCRIMINATION; MOTOR RECOVERY; HAND FUNCTION; BRAIN IMAGES; DEGENERATION AB Frontoparietal white matter supports information transfer between brain areas involved in complex haptic tasks such as somatosensory discrimination. The purpose of this study was to gain an understanding of the relationship between microstructural integrity of frontoparietal network white matter and haptic performance in persons with chronic stroke and to compare frontoparietal network integrity in participants with stroke and age matched control participants. Nineteen individuals with stroke and 16 controls participated. Haptic performance was quantified using the Hand Active Sensation Test (HASTe), an 18-itemmatch-to-sample test of weight and texture discrimination. Three tesla MRI was used to obtain diffusion-weighted and high-resolution anatomical images of the whole brain. Probabilistic tractography was used to define 10 frontoparietal tracts total; Four intrahemispheric tracts measured bilaterally 1) thalamus to primary somatosensory cortex (T-S1), 2) thalamus to primary motor cortex (T-M1), 3) primary to secondary somatosensory cortex (S1 to SII) and 4) primary somatosensory cortex to middle frontal gyrus (S1 to MFG) and, 2 interhemispheric tracts; S1-S1 and precuneus interhemispheric. A control tract outside the network, the cuneus interhemispheric tract, was also examined. The diffusion metrics fractional anisotropy (FA), mean diffusivity (MD), axial (AD) and radial diffusivity (RD) were quantified for each tract. Diminished FA and elevated MD values are associated with poorer white matter integrity in chronic stroke. Nine of 10 tracts quantified in the frontoparietal network had diminished structural integrity poststroke compared to the controls. The precuneus interhemispheric tract was not significantly different between groups. Principle component analysis across all frontoparietal white matter tract MD values indicated a single factor explained 47% and 57% of the variance in tract mean diffusivity in stroke and control groups respectively. Age strongly correlated with the shared variance across tracts in the control, but not in the poststroke participants. A moderate to good relationship was found between ipsilesional T-M1 MD and affected hand HASTe score (r=-0.62, p=0.006) and less affected hand HASTe score (r=-0.53, p=0.022). Regression analysis revealed approximately 90% of the variance in affected hand HASTe score was predicted by the white matter integrity in the frontoparietal network (as indexed by MD) in poststroke participants while 87% of the variance in HASTe score was predicted in control participants. This study demonstrates the importance of frontoparietal white matter in mediating haptic performance and specifically identifies that T-M1 and precuneus interhemispheric tracts may be appropriate targets for piloting rehabilitation interventions, such as noninvasive brain stimulation, when the goal is to improve poststroke haptic performance. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Borstad, Alexandra L.] Ohio State Univ, Div Phys Therapy, Sch Hlth & Rehabil Sci, 453 W 10th Ave, Columbus, OH 43210 USA. [Choi, Seongjin] NIA, Harbor Hosp, Baltimore, MD 21224 USA. [Schmalbrock, Petra] Ohio State Univ, Coll Med, Dept Radiol, Columbus, OH 43210 USA. [Nichols-Larsen, Deborah S.] Ohio State Univ, Sch Hlth & Rehabil Sci, Columbus, OH 43210 USA. RP Borstad, AL (reprint author), Ohio State Univ, Div Phys Therapy, Sch Hlth & Rehabil Sci, 453 W 10th Ave, Columbus, OH 43210 USA. EM Borstad.2@osu.edu; seongjin.choi@nih.gov; Schmalbrock.1@osu.edu; Larsen.64@osu.edu FU PODS I scholarship from Foundation for Physical Therapy, Inc.; Ohio State University Neuroscience Signature Program; OSU Center for Clinical and Translational Research award from National Center for Research Resources [TL RR025753]; Office of the Director, National Institutes of Health; NIH Road map for Medical Research FX This work was supported in part by a PODS I scholarship from the Foundation for Physical Therapy, Inc.; also The Ohio State University Neuroscience Signature Program and The OSU Center for Clinical and Translational Research award number TL RR025753 from the National Center for Research Resources, funded by the Office of the Director, National Institutes of Health and supported by the NIH Road map for Medical Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 79 TC 1 Z9 1 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2016 VL 10 BP 129 EP 139 DI 10.1016/j.nicl.2015.11.007 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA DI0LX UT WOS:000373189000015 PM 26759788 ER PT J AU Matsumoto, A Sakamoto, C Matsumori, H Katahira, J Yasuda, Y Yoshidome, K Tsujimoto, M Goldberg, IG Matsuura, N Nakao, M Saitoh, N Hieda, M AF Matsumoto, Ayaka Sakamoto, Chiyomi Matsumori, Haruka Katahira, Jun Yasuda, Yoko Yoshidome, Katsuhide Tsujimoto, Masahiko Goldberg, Ilya G. Matsuura, Nariaki Nakao, Mitsuyoshi Saitoh, Noriko Hieda, Miki TI Loss of the integral nuclear envelope protein SUN1 induces alteration of nucleoli SO NUCLEUS LA English DT Article DE breast cancer; LINC complex; lamin A; C; nuclear morphology; nuclear envelope; SUN1; SUN2; wndchrm ID RIBOSOMAL-RNA SYNTHESIS; DNA-DAMAGE RESPONSE; LAMIN A/C; BREAST-CANCER; DOMAIN ORGANIZATION; IMAGE-ANALYSIS; LINC COMPLEX; YEAST; CHROMOSOMES; BIOGENESIS AB A supervised machine learning algorithm, which is qualified for image classification and analyzing similarities, is based on multiple discriminative morphological features that are automatically assembled during the learning processes. The algorithm is suitable for population-based analysis of images of biological materials that are generally complex and heterogeneous. Here we used the algorithm wndchrm to quantify the effects on nucleolar morphology of the loss of the components of nuclear envelope in a human mammary epithelial cell line. The linker of nucleoskeleton and cytoskeleton (LINC) complex, an assembly of nuclear envelope proteins comprising mainly members of the SUN and nesprin families, connects the nuclear lamina and cytoskeletal filaments. The components of the LINC complex are markedly deficient in breast cancer tissues. We found that a reduction in the levels of SUN1, SUN2, and lamin A/C led to significant changes in morphologies that were computationally classified using wndchrm with approximately 100% accuracy. In particular, depletion of SUN1 caused nucleolar hypertrophy and reduced rRNA synthesis. Further, wndchrm revealed a consistent negative correlation between SUN1 expression and the size of nucleoli in human breast cancer tissues. Our unbiased morphological quantitation strategies using wndchrm revealed an unexpected link between the components of the LINC complex and the morphologies of nucleoli that serves as an indicator of the malignant phenotype of breast cancer cells. C1 [Matsumoto, Ayaka; Matsuura, Nariaki; Hieda, Miki] Osaka Univ, Grad Sch Med & Hlth Sci, Yamadaoka 1-7, Suita, Osaka 5650871, Japan. [Sakamoto, Chiyomi; Matsumori, Haruka; Yasuda, Yoko; Nakao, Mitsuyoshi; Saitoh, Noriko] Kumamoto Univ, Dept Med Cell Biol, Inst Mol Embryol & Genet, Kumamoto, Japan. [Katahira, Jun] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka, Japan. [Yoshidome, Katsuhide] Osaka Police Hosp, Dept Breast Surg, Tennoji Ku, Osaka, Japan. [Tsujimoto, Masahiko] Osaka Police Hosp, Dept Pathol, Tennoji Ku, Osaka, Japan. [Goldberg, Ilya G.] NIA, Image Informat & Computat Biol Unit, Genet Lab, NIH, Baltimore, MD 21224 USA. [Nakao, Mitsuyoshi] Japan Agcy Med Res & Dev, CREST, Tokyo, Japan. RP Hieda, M (reprint author), Osaka Univ, Grad Sch Med & Hlth Sci, Yamadaoka 1-7, Suita, Osaka 5650871, Japan.; Saitoh, N (reprint author), Kumamoto Univ, Inst Mol Embryol & Genet, Dept Med Cell Biol, Chuo Ku, 2-2-1 Honjo, Kumamoto 8600811, Japan. EM norikos@kumamoto-u.ac.jp; mikihieda@gmail.com OI Goldberg, Ilya/0000-0001-8514-6110; Hieda, Miki/0000-0002-9492-7506 FU Joint Usage/Research Center for Developmental Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University; Japan Society for the Promotion of Science; Ministry of Education, Culture, Sports, Science and Technology of Japan FX This work was supported by the Joint Usage/Research Center for Developmental Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University, by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science to MH and NS, and by a Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan to NS. NR 65 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 1949-1034 EI 1949-1042 J9 NUCLEUS-PHILA JI Nucleus PY 2016 VL 7 IS 1 BP 68 EP 83 DI 10.1080/19491034.2016.1149664 PG 16 WC Cell Biology SC Cell Biology GA DI4PS UT WOS:000373482400009 PM 26962703 ER PT J AU Anuradha, R Munisankar, S Bhootra, Y Jagannathan, J Dolla, C Kumaran, P Nutman, TB Babu, S AF Anuradha, Rajamanickam Munisankar, Saravanan Bhootra, Yukthi Jagannathan, Jeeva Dolla, Chandrakumar Kumaran, Paul Nutman, Thomas B. Babu, Subash TI IL-10-and TGF beta-mediated Th9 Responses in a Human Helminth Infection SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID STRONGYLOIDES-STERCORALIS INFECTION; HELPER 9 CELLS; T-CELLS; IMMUNE-RESPONSE; TRICHURIS-MURIS; INTERLEUKIN-9; MICE; DIFFERENTIATION; EOSINOPHILIA; DISEASE AB Background Th9 cells are a subset of CD4(+) T cells that express the protoypical cytokine, IL-9. Th9 cells are known to effect protective immunity in animal models of intestinal helminth infections. However, the role of Th9 cells in human intestinal helminth infections has never been examined. Methodology To examine the role of Th9 cells in Strongyloidis stercoralis (Ss), a common intestinal helminth infection, we compared the frequency of Th9 expressing IL-9 either singly (monofunctional) or co-expressing IL-4 or IL-10 (dual-functional) in Ss-infected individuals (INF) to frequencies in uninfected (UN) individuals. Principal Findings INF individuals exhibited a significant increase in the spontaneously expressed and/or antigen specific frequencies of both mono-and dual-functional Th9 cells as well as Th2 cells expressing IL-9 compared to UN. The differences in Th9 induction between INF and UN individuals was predominantly antigen-specific as the differences were no longer seen following control antigen or mitogen stimulation. In addition, the increased frequency of Th9 cells in response to parasite antigens was dependent on IL-10 and TGFx since neutralization of either of these cytokines resulted in diminished Th9 frequencies. Finally, following successful treatment of Ss infection, the frequencies of antigen-specific Th9 cells diminished in INF individuals, suggesting a role for the Th9 response in active Ss infection. Moreover, IL-9 levels in whole blood culture supernatants following Ss antigen stimulation were higher in INF compared to UN individuals. Conclusion Thus, Ss infection is characterized by an IL-10- and TGF beta dependent expansion of Th9 cells, an expansion found to reversible by anti-helmintic treatment. C1 [Anuradha, Rajamanickam; Munisankar, Saravanan; Bhootra, Yukthi; Jagannathan, Jeeva; Babu, Subash] Int Ctr Excellence Res, Natl Inst Hlth, NIRT, Madras, Tamil Nadu, India. [Dolla, Chandrakumar; Kumaran, Paul] Natl Inst Res TB, Madras, Tamil Nadu, India. [Nutman, Thomas B.; Babu, Subash] NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Babu, S (reprint author), Int Ctr Excellence Res, Natl Inst Hlth, NIRT, Madras, Tamil Nadu, India.; Babu, S (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM sbabu@mail.nih.gov FU Division of Intramural Research, NIAID, NIH FX This work was supported by the Division of Intramural Research, NIAID, NIH. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 30 TC 4 Z9 6 U1 2 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2016 VL 10 IS 1 AR e0004317 DI 10.1371/journal.pntd.0004317 PG 13 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DH1SR UT WOS:000372565700032 PM 26730582 ER PT J AU Assumpcao, TC Ma, DY Mizurini, DM Kini, RM Ribeiro, JMC Kotsyfakis, M Monteiro, RQ Francischetti, IMB AF Assumpcao, Teresa C. Ma, Dongying Mizurini, Daniella M. Kini, R. Manjunatha Ribeiro, Jose M. C. Kotsyfakis, Michail Monteiro, Robson Q. Francischetti, Ivo M. B. TI In Vitro Mode of Action and Anti-thrombotic Activity of Boophilin, a Multifunctional Kunitz Protease Inhibitor from the Midgut of a Tick Vector of Babesiosis, Rhipicephalus microplus SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID THROMBIN INHIBITOR; PLATELET-AGGREGATION; SALIVARY-GLAND; ANTICOAGULANT PROTEIN; HEMATOPHAGOUS ANIMALS; CRYSTAL-STRUCTURE; TISSUE FACTOR; BLOOD INTAKE; CATTLE TICK; FACTOR-XI AB Background Hematophagous mosquitos and ticks avoid host hemostatic system through expression of enzyme inhibitors targeting proteolytic reactions of the coagulation and complement cascades. While most inhibitors characterized to date were found in the salivary glands, relatively few others have been identified in the midgut. Among those, Boophilin is a 2-Kunitz multifunctional inhibitor targeting thrombin, elastase, and kallikrein. However, the kinetics of Boophilin interaction with these enzymes, how it modulates platelet function, and whether it inhibits thrombosis in vivo have not been determined. Methodology/Principal Findings Boophilin was expressed in HEK293 cells and purified to homogeneity. Using amidolytic assays and surface plasmon resonance experiments, we have demonstrated that Boophilin behaves as a classical, non-competitive inhibitor of thrombin with respect to small chromogenic substrates by a mechanism dependent on both exosite-1 and catalytic site. Inhibition is accompanied by blockade of platelet aggregation, fibrin formation, and clot-bound thrombin in vitro. Notably, we also identified Boophilin as a non-competitive inhibitor of FXIa, preventing FIX activation. In addition, Boophilin inhibits kallikrein activity and the reciprocal activation, indicating that it targets the contact pathway. Furthermore, Boophilin abrogates cathepsin G-and plasmin-induced platelet aggregation and partially affects elastase-mediated cleavage of Tissue Factor Pathway Inhibitor (TFPI). Finally, Boophilin inhibits carotid artery occlusion in vivo triggered by FeCl3, and promotes bleeding according to the mice tail transection method. Conclusion/Significance Through inhibition of several enzymes involved in proteolytic cascades and cell activation, Boophilin plays a major role in keeping the midgut microenvironment at low hemostatic and inflammatory tonus. This response allows ticks to successfully digest a blood meal which is critical for metabolism and egg development. Boophilin is the first tick midgut FXIa anticoagulant also found to inhibit thrombosis. C1 [Assumpcao, Teresa C.; Ma, Dongying; Ribeiro, Jose M. C.; Francischetti, Ivo M. B.] NIAID, Vector Biol Sect, LMVR, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Mizurini, Daniella M.; Monteiro, Robson Q.] Univ Fed Rio de Janeiro, Inst Bioquim Med Leopoldo Meis, Rio De Janeiro, Brazil. [Kini, R. Manjunatha] Natl Univ Singapore, Dept Biol Sci, Prot Sci Lab, Singapore 117548, Singapore. [Kotsyfakis, Michail] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, Branisovska 31, CR-37005 Ceske Budejovice, Czech Republic. [Francischetti, Ivo M. B.] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Pathol, Bronx, NY 10467 USA. RP Francischetti, IMB (reprint author), NIAID, Vector Biol Sect, LMVR, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.; Francischetti, IMB (reprint author), Albert Einstein Coll Med, Montefiore Med Ctr, Dept Pathol, Bronx, NY 10467 USA. EM ivofrancischetti@gmail.com RI Kotsyfakis, Michail/G-9525-2014; Monteiro, Robson/B-8007-2014; OI Kotsyfakis, Michail/0000-0002-7526-1876; Ribeiro, Jose/0000-0002-9107-0818 FU US National Institutes of Health; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico; Czech Academy of Sciences FX Funds were from: US National Institutes of Health (JMCR), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (RQM), and Czech Academy of Sciences (MK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 5 Z9 5 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2016 VL 10 IS 1 AR e0004298 DI 10.1371/journal.pntd.0004298 PG 20 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DH1SR UT WOS:000372565700019 PM 26745503 ER PT J AU Fiuza, JA Dey, R Davenport, D Abdeladhim, M Meneses, C Oliveira, F Kamhawi, S Valenzuela, JG Gannavaram, S Nakhasi, HL AF Fiuza, Jacqueline Araujo Dey, Ranadhir Davenport, Dwann Abdeladhim, Maha Meneses, Claudio Oliveira, Fabiano Kamhawi, Shaden Valenzuela, Jesus G. Gannavaram, Sreenivas Nakhasi, Hira L. TI Intradermal Immunization of Leishmania donovani Centrin Knock-Out Parasites in Combination with Salivary Protein LJM19 from Sand Fly Vector Induces a Durable Protective Immune Response in Hamsters SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID EXPERIMENTAL VISCERAL LEISHMANIASIS; LUTZOMYIA-LONGIPALPIS SALIVA; DELETED PARASITES; VACCINATION; MEXICANA; CELLS; INFECTIONS; INFANTUM; MICE; INTERLEUKIN-12 AB Background Visceral leishmaniasis (VL) is a neglected tropical disease and is fatal if untreated. There is no vaccine available against leishmaniasis. The majority of patients with cutaneous leishmaniasis (CL) or VL develop a long-term protective immunity after cure from infection, which indicates that development of an effective vaccine against leishmaniasis is possible. Such protection may also be achieved by immunization with live attenuated parasites that do not cause disease. We have previously reported a protective response in mice, hamsters and dogs with Leishmania donovani centrin gene knock-out parasites (LdCen(-/-)), a live attenuated parasite with a cell division specific centrin1 gene deletion. In this study we have explored the effects of salivary protein LJM19 as an adjuvant and intradermal (ID) route of immunization on the efficacy of LdCen(-/-) parasites as a vaccine against virulent L. donovani. Methodology/Principal Findings To explore the potential of a combination of LdCen(-/-) parasites and salivary protein LJM19 as vaccine antigens, LdCen(-/-) ID immunization followed by ID challenge with virulent L. donovani were performed in hamsters in a 9-month follow up study. We determined parasite burden (serial dilution), antibody production (ELISA) and cytokine expression (qPCR) in these animals. Compared to controls, animals immunized with LdCen(-/-) + LJM19 induced a strong antibody response, a reduction in spleen and liver parasite burden and a higher expression of pro-inflammatory cytokines after immunization and one month post-challenge. Additionally, a low parasite load in lymph nodes, spleen and liver, and a non-inflamed spleen was observed in immunized animals 9 months after the challenge infection. Conclusions Our results demonstrate that an ID vaccination using LdCen(-/-) parasites in combination with sand fly salivary protein LJM19 has the capability to confer long lasting protection against visceral leishmaniasis that is comparable to intravenous or intracardial immunization. C1 [Fiuza, Jacqueline Araujo; Dey, Ranadhir; Davenport, Dwann; Gannavaram, Sreenivas; Nakhasi, Hira L.] US FDA, Lab Emerging Pathogens, Ctr Biol Evaluat & Res, Silver Spring, MD USA. [Fiuza, Jacqueline Araujo] Ctr Pesquisas Rene Rachou Fiocruz Minas, Lab Imunol Celular & Mol, Belo Horizonte, MG, Brazil. [Abdeladhim, Maha; Meneses, Claudio; Oliveira, Fabiano; Kamhawi, Shaden; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Gannavaram, S; Nakhasi, HL (reprint author), US FDA, Lab Emerging Pathogens, Ctr Biol Evaluat & Res, Silver Spring, MD USA. EM sreenivas.gannavaram@fda.hhs.gov; hira.nakhasi@fda.hhs.gov FU Intramural Research Program at National Institute of Allergy and Infectious Diseases, NIH; Center for Biologics Evaluation and Research, FDA FX This research was supported in part by the Intramural Research Program at the National Institute of Allergy and Infectious Diseases, NIH (JGV SK FO MA) and Center for Biologics Evaluation and Research, FDA (JAF RD SG HLN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 3 Z9 3 U1 2 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2016 VL 10 IS 1 AR e0004322 DI 10.1371/journal.pntd.0004322 PG 17 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DH1SR UT WOS:000372565700035 PM 26752686 ER PT J AU Golden, A Stevens, EJ Yokobe, L Faulx, D Kalnoky, M Peck, R Valdez, M Steel, C Karabou, P Banla, M Soboslay, PT Adade, K Tekle, AH Cama, VA Fischer, PU Nutman, TB Unnasch, TR de los Santos, T Domingo, GJ AF Golden, Allison Stevens, Eric J. Yokobe, Lindsay Faulx, Dunia Kalnoky, Michael Peck, Roger Valdez, Melissa Steel, Cathy Karabou, Potochoziou Banla, Meba Soboslay, Peter T. Adade, Kangi Tekle, Afework H. Cama, Vitaliano A. Fischer, Peter U. Nutman, Thomas B. Unnasch, Thomas R. de los Santos, Tala Domingo, Gonzalo J. TI A Recombinant Positive Control for Serology Diagnostic Tests Supporting Elimination of Onchocerca volvulus SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID ANTIBODY-TEST; TRANSMISSION; INFECTION; FOCUS; INTERRUPTION; PURIFICATION; PROTEINS; LIBRARY; ANTIGEN; MARKER AB Background Serological assays for human IgG4 to the Onchocerca volvulus antigen Ov16 have been used to confirm elimination of onchocerciasis in much of the Americas and parts of Africa. A standardized source of positive control antibody (human anti-Ov16 IgG4) will ensure the quality of surveillance data using these tests. Methodology/Principal Findings A recombinant human IgG4 antibody to Ov16 was identified by screening against a synthetic human Fab phage display library and converted into human IgG4. This antibody was developed into different positive control formulations for enzyme-linked immunosorbent assay (ELISA) and rapid diagnostic test (RDT) platforms. Variation in ELISA results and utility as a positive control of the antibody were assessed from multiple laboratories. Temperature and humidity conditions were collected across seven surveillance activities from 20112014 to inform stability requirements for RDTs and positive controls. The feasibility of the dried positive control for RDT was evaluated during onchocerciasis surveillance activity in Togo, in 2014. When the anti-Ov16 IgG4 antibody was used as a standard dilution in horseradish peroxidase (HRP) and alkaline phosphatase (AP) ELISAs, the detection limits were approximately 1ng/mL by HRP ELISA and 10ng/mL by AP ELISA. Positive control dilutions and spiked dried blood spots (DBS) produced similar ELISA results. Used as a simple plate normalization control, the positive control antibody may improve ELISA data comparison in the context of inter-laboratory variation. The aggregate temperature and humidity monitor data informed temperature parameters under which the dried positive control was tested and are applicable inputs for testing of diagnostics tools intended for sub-Saharan Africa. As a packaged positive control for Ov16 RDTs, stability of the antibody was demonstrated for over six months at relevant temperatures in the laboratory and for over 15 weeks under field conditions. Conclusions The recombinant human anti-Ov16 IgG4 antibody-based positive control will benefit inter-laboratory validation of ELISA assays and serve as quality control (QC) reagents for Ov16 RDTs at different points of the supply chain from manufacturer to field use. C1 [Golden, Allison; Stevens, Eric J.; Yokobe, Lindsay; Faulx, Dunia; Kalnoky, Michael; Peck, Roger; Valdez, Melissa; de los Santos, Tala; Domingo, Gonzalo J.] PATH, Diagnost Global Program, Seattle, WA USA. [Steel, Cathy; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Karabou, Potochoziou; Adade, Kangi] Natl Onchocerciasis Control Programme, Kara, Togo. [Banla, Meba; Soboslay, Peter T.] Natl Inst Hyg, Onchocerciasis Reference Lab, Sokode, Togo. [Soboslay, Peter T.] Univ Clin Tubingen, Inst Trop Med, Tubingen, Germany. [Tekle, Afework H.] WHO, African Programme Onchocerciasis Control, Ouagadougou, Burkina Faso. [Cama, Vitaliano A.] Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Atlanta, GA USA. [Fischer, Peter U.] Washington Univ, Sch Med, Dept Internal Med, Div Infect Dis, St Louis, MO 63110 USA. [Unnasch, Thomas R.] Univ S Florida, Dept Global Hlth, Global Hlth Infect Dis Res Program, Tampa, FL USA. RP Golden, A (reprint author), PATH, Diagnost Global Program, Seattle, WA USA. EM algolden@path.org FU Bill and Melinda Gates Foundation [OPP1017876] FX This work was funded by Bill and Melinda Gates Foundation grant OPP1017876 received by TdlS, PATH, Director, Diagnostics Global Program and Project Lead. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 1 Z9 1 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2016 VL 10 IS 1 AR e0004292 DI 10.1371/journal.pntd.0004292 PG 16 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DH1SR UT WOS:000372565700017 PM 26745374 ER PT J AU Lord, JS Al-Amin, HM Chakma, S Alam, MS Gurley, ES Pulliam, JRC AF Lord, Jennifer S. Al-Amin, Hasan Mohammad Chakma, Sumit Alam, Mohammad Shafiul Gurley, Emily S. Pulliam, Juliet R. C. TI Sampling Design Influences the Observed Dominance of Culex tritaeniorhynchus: Considerations for Future Studies of Japanese Encephalitis Virus Transmission SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID ADULT MOSQUITO ABUNDANCE; ANDHRA-PRADESH; KURNOOL DISTRICT; SOUTH-INDIA; TAMIL-NADU; SEASONAL PREVALENCE; VECTOR ABUNDANCE; BELLARY DISTRICT; HOST PREFERENCES; DISEASE-CONTROL AB Mosquito sampling during Japanese encephalitis virus (JEV)-associated studies, particularly in India, has usually been conducted via aspirators or light traps to catch mosquitoes around cattle, which are dead-end hosts for JEV. High numbers of Culex tritaeniorhynchus, relative to other species, have often been caught during these studies. Less frequently, studies have involved sampling outdoor resting mosquitoes. We aimed to compare the relative abundance of mosquito species between these two previously used mosquito sampling methods. From September to December 2013 entomological surveys were undertaken in eight villages in a Japanese encephalitis (JE) endemic area of Bangladesh. Light traps were used to collect active mosquitoes in households, and resting boxes and a Bina Pani Das hop cage were used near oviposition sites to collect resting mosquitoes. Numbers of humans and domestic animals present in households where light traps were set were recorded. In five villages Cx. tritaeniorhynchus was more likely to be selected from light trap samples near hosts than resting collection samples near oviposition sites, according to log odds ratio tests. The opposite was true for Cx. pseudovishnui and Armigeres subalbatus, which can also transmit JEV. Culex tritaeniorhynchus constituted 59% of the mosquitoes sampled from households with cattle, 28% from households without cattle and 17% in resting collections. In contrast Cx. pseudovishnui constituted 5.4% of the sample from households with cattle, 16% from households with no cattle and 27% from resting collections, while Ar. subalbatus constituted 0.15%, 0.38%, and 8.4% of these samples respectively. These observations may be due to differences in timing of biting activity, host preference and host-seeking strategy rather than differences in population density. We suggest that future studies aiming to implicate vector species in transmission of JEV should consider focusing catches around hosts able to transmit JEV. C1 [Lord, Jennifer S.] Univ Liverpool, Liverpool Sch Trop Med, Vector Grp, Liverpool L3 5QA, Merseyside, England. [Lord, Jennifer S.; Pulliam, Juliet R. C.] Univ Florida, Dept Biol, Gainesville, FL USA. [Al-Amin, Hasan Mohammad; Chakma, Sumit; Alam, Mohammad Shafiul; Gurley, Emily S.] Icddr b, Ctr Communicable Dis, Dhaka, Bangladesh. [Pulliam, Juliet R. C.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA. [Pulliam, Juliet R. C.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. RP Lord, JS (reprint author), Univ Liverpool, Liverpool Sch Trop Med, Vector Grp, Liverpool L3 5QA, Merseyside, England.; Lord, JS (reprint author), Univ Florida, Dept Biol, Gainesville, FL USA. EM jennifer.suzanne.lord@gmail.com RI Pulliam, Juliet/A-6516-2008; Gurley, Emily/B-7903-2010 OI Pulliam, Juliet/0000-0003-3314-8223; Gurley, Emily/0000-0002-8648-9403 FU Emerging Pathogens Institute, University of Florida; Research and Policy for Infectious Disease Dynamics (RAPIDD) program; Government of Australia; Government of Bangladesh; Government of Canada; Government of Sweden; Government of UK; Research and Policy on Infectious Disease Dynamics (RAPIDD) Program of Fogarty International Center, National Institutes of Health; Science and Technology Directorate, Department of Homeland Security FX At the time of writing this manuscript Jennifer Lord was a postdoctoral research associate in the Pulliam Lab at the University of Florida. We would like to acknowledge the Emerging Pathogens Institute, University of Florida for funding the fieldwork associated with this study. We would also like to acknowledge funding for a Japanese encephalitis workshop held in October 2012 by the Research and Policy for Infectious Disease Dynamics (RAPIDD) program. icddr, b is thankful to the Governments of Australia, Bangladesh, Canada, Sweden and the UK for providing core support. JRCP and ESG are supported by the Research and Policy on Infectious Disease Dynamics (RAPIDD) Program of the Fogarty International Center, National Institutes of Health and Science and Technology Directorate, Department of Homeland Security. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 71 TC 2 Z9 2 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2016 VL 10 IS 1 AR e0004249 DI 10.1371/journal.pntd.0004249 PG 16 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DH1SR UT WOS:000372565700008 PM 26726881 ER PT J AU McCarthy, SDS Majchrzak-Kita, B Racine, T Kozlowski, HN Baker, DP Hoenen, T Kobinger, GP Fish, EN Branch, DR AF McCarthy, Stephen D. S. Majchrzak-Kita, Beata Racine, Trina Kozlowski, Hannah N. Baker, Darren P. Hoenen, Thomas Kobinger, Gary P. Fish, Eleanor N. Branch, Donald R. TI A Rapid Screening Assay Identifies Monotherapy with Interferon-beta and Combination Therapies with Nucleoside Analogs as Effective Inhibitors of Ebola Virus SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID LAMIVUDINE; TENOFOVIR; SAFETY; TRANSCRIPTION; REPLICATION; FILOVIRUSES; PROTECTION; EFFICACY; DISEASES; SYSTEMS AB To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD). While a number of candidate drugs have shown limited efficacy in vitro and/or in non-human primate studies, differences in experimental methodologies make it difficult to compare their therapeutic effectiveness. Using an in vitro model of Ebola Zaire replication with transcription-competent virus like particles (trVLPs), requiring only level 2 biosafety containment, we compared the activities of the type I interferons (IFNs) IFN-alpha and IFN-beta, a panel of viral polymerase inhibitors (lamivudine (3TC), zidovudine (AZT) tenofovir (TFV), favipiravir (FPV), the active metabolite of brincidofovir, cidofovir (CDF)), and the estrogen receptor modulator, toremifene (TOR), in inhibiting viral replication in dose-response and time course studies. We also tested 28 two-and 56 three-drug combinations against Ebola replication. IFN-alpha and IFN-beta inhibited viral replication 24 hours post-infection (IC50 0.038 mu M and 0.016 mu M, respectively). 3TC, AZT and TFV inhibited Ebola replication when used alone (50-62%) or in combination (87%). They exhibited lower IC50 (0.98-6.2 mu M) compared with FPV (36.8 mu M), when administered 24 hours post-infection. Unexpectedly, CDF had a narrow therapeutic window (6.25-25 mu M). When dosed >50 mu M, CDF treatment enhanced viral infection. IFN-beta exhibited strong synergy with 3TC (97.3% inhibition) or in triple combination with 3TC and AZT (95.8% inhibition). This study demonstrates that IFNs and viral polymerase inhibitors may have utility in EVD. We identified several 2 and 3 drug combinations with strong anti-Ebola activity, confirmed in studies using fully infectious ZEBOV, providing a rationale for testing combination therapies in animal models of lethal Ebola challenge. These studies open up new possibilities for novel therapeutic options, in particular combination therapies, which could prevent and treat Ebola infection and potentially reduce drug resistance. C1 [McCarthy, Stephen D. S.; Kozlowski, Hannah N.; Branch, Donald R.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Majchrzak-Kita, Beata; Fish, Eleanor N.; Branch, Donald R.] Toronto Gen Res Inst, Infect & Immun Grp, Div Adv Diagnost, Toronto, ON, Canada. [Racine, Trina; Kobinger, Gary P.] Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada. [Baker, Darren P.] Biogen, Cambridge, MA USA. [Hoenen, Thomas] NIAID, Virol Lab, NIH, Hamilton, MT USA. [Fish, Eleanor N.] Univ Toronto, Dept Immunol, Toronto, ON, Canada. [Branch, Donald R.] Canadian Blood Serv, Ctr Innovat, Toronto, ON, Canada. RP Fish, EN (reprint author), Toronto Gen Res Inst, Infect & Immun Grp, Div Adv Diagnost, Toronto, ON, Canada.; Fish, EN (reprint author), Univ Toronto, Dept Immunol, Toronto, ON, Canada. EM en.fish@utoronto.ca FU Canadian Institutes of Health Research [IET 138898]; intramural research program of the NIH, NIAID; Health Canada FX These studies were supported by a Canadian Institutes of Health Research grant IET 138898 to ENF; ENF is a Tier 1 Canada Research Chair. TH was in part funded by the intramural research program of the NIH, NIAID. SDSM is a recipient of Vanier CGS D and Canadian Blood Services GFP graduate awards. DRB is partially funded through support provided by Health Canada, but the views expressed herein do not necessarily represent the view of the federal government of Canada. The funders had no role in study design, data collection and analyses, decision to publish, or preparation of the manuscript. NR 33 TC 6 Z9 6 U1 2 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2016 VL 10 IS 1 AR e0004364 DI 10.1371/journal.pntd.0004364 PG 16 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DH1SR UT WOS:000372565700063 PM 26752302 ER PT J AU West, SK Munoz, B Weaver, J Mrango, Z Dize, L Gaydos, C Quinn, TC Martin, DL AF West, Sheila K. Munoz, Beatriz Weaver, Jerusha Mrango, Zakayo Dize, Laura Gaydos, Charlotte Quinn, Thomas C. Martin, Diana L. TI Can We Use Antibodies to Chlamydia trachomatis as a Surveillance Tool for National Trachoma Control Programs? Results from a District Survey SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID COMMUNITIES; REDUCTION; GAMBIA AB Background Trachoma is targeted for elimination by 2020. World Health Organization advises districts to undertake surveillance when follicular trachoma (TF) < 5% in children 1-9 years and mass antibiotic administration has ceased. There is a question if other tools could be used for surveillance as well. We report data from a test for antibodies to C. trachomatis antigen pgp3 as a possible tool. Methodology We randomly sampled 30 hamlets in Kilosa district, Tanzania, and randomly selected 50 children ages 1-9 per hamlet. The tarsal conjunctivae were graded for trachoma (TF), tested for C. trachomatis infection (Aptima Combo2 assay: Hologic, San Diego, CA), and a dried blood spot processed for antibodies to C. trachomatis pgp3 using a multiplex bead assay on a Luminex 100 platform. Principal findings The prevalence of trachoma (TF) was 0.4%, well below the < 5% indicator for re-starting a program. Infection was also low, 1.1%. Of the 30 hamlets, 22 had neither infection nor TF. Antibody positivity overall was low, 7.5% and increased with age from 5.2% in 1-3 year olds, to 9.3% in 7-9 year olds (p = 0.015). In 16 of the 30 hamlets, no children ages 1-3 years had antibodies to pgp3. Conclusions The antibody status of the 1-3 year olds indicates low cumulative exposure to infection during the surveillance period. Four years post MDA, there is no evidence for re-emergence of follicular trachoma. C1 [West, Sheila K.; Munoz, Beatriz; Weaver, Jerusha] Johns Hopkins Univ, Dana Ctr Prevent Ophthalmol, Baltimore, MD USA. [Mrango, Zakayo] Natl Inst Med Res, Kilosa, Tanzania. [Dize, Laura; Gaydos, Charlotte; Quinn, Thomas C.] Johns Hopkins Univ, Div Infect Dis, Baltimore, MD USA. [Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD USA. [Martin, Diana L.] Ctr Dis Control & Prevent, Atlanta, GA USA. RP West, SK (reprint author), Johns Hopkins Univ, Dana Ctr Prevent Ophthalmol, Baltimore, MD USA. EM shwest@jhmi.edu FU Bill and Melinda Gates Foundation; Division of Intramural Research, National Institute of Allergy and Infectious Diseases FX Funding was provided by the Bill and Melinda Gates Foundation through a grant to the Task Force for Global Health, and in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 14 TC 2 Z9 2 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2016 VL 10 IS 1 AR e0004352 DI 10.1371/journal.pntd.0004352 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DH1SR UT WOS:000372565700056 PM 26771906 ER PT J AU Winglee, K McGuire, AM Maiga, M Abeel, T Shea, T Desjardins, CA Diarra, B Baya, B Sanogo, M Diallo, S Earl, AM Bishai, WR AF Winglee, Kathryn McGuire, Abigail Manson Maiga, Mamoudou Abeel, Thomas Shea, Terrance Desjardins, Christopher A. Diarra, Bassirou Baya, Bocar Sanogo, Moumine Diallo, Souleymane Earl, Ashlee M. Bishai, William R. TI Whole Genome Sequencing of Mycobacterium africanum Strains from Mali Provides Insights into the Mechanisms of Geographic Restriction SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID GENOTYPE MTBDRSL ASSAY; TUBERCULOSIS COMPLEX STRAINS; GENETIC DIVERSITY; WEST-AFRICAN; STREPTOMYCIN RESISTANCE; VITAMIN-B-12 METABOLISM; MOLECULAR EPIDEMIOLOGY; ETHAMBUTOL RESISTANCE; PROTEIN FAMILIES; ATP SYNTHASE AB Background Mycobacterium africanum, made up of lineages 5 and 6 within the Mycobacterium tuberculosis complex (MTC), causes up to half of all tuberculosis cases in West Africa, but is rarely found outside of this region. The reasons for this geographical restriction remain unknown. Possible reasons include a geographically restricted animal reservoir, a unique preference for hosts of West African ethnicity, and an inability to compete with other lineages outside of West Africa. These latter two hypotheses could be caused by loss of fitness or altered interactions with the host immune system. Methodology/Principal Findings We sequenced 92 MTC clinical isolates from Mali, including two lineage 5 and 24 lineage 6 strains. Our genome sequencing assembly, alignment, phylogeny and average nucleotide identity analyses enabled us to identify features that typify lineages 5 and 6 and made clear that these lineages do not constitute a distinct species within the MTC. We found that in Mali, lineage 6 and lineage 4 strains have similar levels of diversity and evolve drug resistance through similar mechanisms. In the process, we identified a putative novel streptomycin resistance mutation. In addition, we found evidence of person-to-person transmission of lineage 6 isolates and showed that lineage 6 is not enriched for mutations in virulence-associated genes. Conclusions This is the largest collection of lineage 5 and 6 whole genome sequences to date, and our assembly and alignment data provide valuable insights into what distinguishes these lineages from other MTC lineages. Lineages 5 and 6 do not appear to be geographically restricted due to an inability to transmit between West African hosts or to an elevated number of mutations in virulence-associated genes. However, lineage-specific mutations, such as mutations in cell wall structure, secretion systems and cofactor biosynthesis, provide alternative mechanisms that may lead to host specificity. C1 [Winglee, Kathryn; Maiga, Mamoudou; Bishai, William R.] Johns Hopkins Univ, Dept Med, Ctr TB Res, Baltimore, MD USA. [McGuire, Abigail Manson; Abeel, Thomas; Shea, Terrance; Desjardins, Christopher A.; Earl, Ashlee M.] Broad Inst MIT & Harvard, Genome Sequencing & Anal Program, Cambridge, MA USA. [Maiga, Mamoudou; Diarra, Bassirou; Baya, Bocar; Sanogo, Moumine; Diallo, Souleymane] USTTB, Project SEREFO, Ctr Rech & Format VIH Sida & TB, Bamako, Mali. [Abeel, Thomas] Delft Univ Technol, Delft Bioinformat Lab, Delft, Netherlands. [Maiga, Mamoudou] NIH, Bldg 10, Bethesda, MD 20892 USA. RP Bishai, WR (reprint author), Johns Hopkins Univ, Dept Med, Ctr TB Res, Baltimore, MD USA.; Earl, AM (reprint author), Broad Inst MIT & Harvard, Genome Sequencing & Anal Program, Cambridge, MA USA. EM aearl@broadinstitute.org; wbishai1@jhmi.edu RI Manson, Abigail/B-7132-2016; OI Manson, Abigail/0000-0002-3800-0714; Earl, Ashlee/0000-0001-7857-9145 FU Federal funds from National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Department of Health and Human Services [HHSN272200900018C, U19AI110818]; Howard Hughes Medical Institute; National Institutes of Health [AI037856, AI036973, AI097138] FX This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Department of Health and Human Services, under Contract No.: HHSN272200900018C and Grant Number U19AI110818 to the Broad Institute. In addition, this work has been funded by the Howard Hughes Medical Institute and the National Institutes of Health grants AI037856, AI036973 and AI097138 to WRB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 113 TC 8 Z9 8 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2016 VL 10 IS 1 AR e0004332 DI 10.1371/journal.pntd.0004332 PG 28 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DH1SR UT WOS:000372565700043 PM 26751217 ER PT J AU Caretti, G Berghella, L Juan, A Latella, L Ryall, J AF Caretti, Giuseppina Berghella, Libera Juan, Aster Latella, Lucia Ryall, James TI Epigenetic Regulation Shapes the Stem Cells State SO STEM CELLS INTERNATIONAL LA English DT Editorial Material C1 [Caretti, Giuseppina] Univ Milan, Dept Biosci, I-20133 Milan, Italy. [Berghella, Libera] IRCCS Fdn Santa Lucia, I-00143 Rome, Italy. [Juan, Aster] NIAMSD, NIH, Bethesda, MD 20892 USA. [Latella, Lucia] CNR, Inst Translat Pharmacol, I-00133 Rome, Italy. [Ryall, James] Univ Melbourne, Basic & Clin Myol Lab, Stem Cell Metab & Regenerat Med Grp, Melbourne, Vic 3010, Australia. RP Caretti, G (reprint author), Univ Milan, Dept Biosci, I-20133 Milan, Italy. EM giuseppina.caretti@unimi.it OI Ryall, James/0000-0003-4702-1143 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-966X EI 1687-9678 J9 STEM CELLS INT JI Stem Cells Int. PY 2016 AR 8143407 DI 10.1155/2016/8143407 PG 2 WC Cell & Tissue Engineering SC Cell Biology GA DH8KJ UT WOS:000373041700001 ER PT J AU Dias, JP Melvin, D Simonsick, EM Carlson, O Shardell, MD Ferrucci, L Chia, CW Basaria, S Egan, JM AF Dias, J. P. Melvin, D. Simonsick, E. M. Carlson, O. Shardell, M. D. Ferrucci, L. Chia, C. W. Basaria, S. Egan, J. M. TI Effects of aromatase inhibition vs. testosterone in older men with low testosterone: randomized-controlled trial SO ANDROLOGY LA English DT Article DE aging; aromatase inhibition; bone; gait speed; muscle strength; testosterone ID LEAN BODY-MASS; BONE-MINERAL DENSITY; ELDERLY-MEN; SERUM TESTOSTERONE; PHYSICAL FUNCTION; TRANSDERMAL TESTOSTERONE; LONGITUDINAL ASSOCIATION; EXOGENOUS TESTOSTERONE; MUSCLE STRENGTH; GRIP STRENGTH AB Aging in men is associated with loss of bone mass, impaired physical function and altered body composition. The objective of this proof-of-concept randomized, double-blind, placebo-controlled, parallel-group, single-center trial was to determine the relative effects of testosterone (T) and estradiol (E2) on bone mineral density, body composition, and physical performance in older men. The primary outcome was lumbar spine bone mineral density (BMD), and secondary outcomes were body composition, muscle strength, gait speed, and sex hormone concentrations. Forty three men (age range, 65-82 years; mean age 71 years) with low total T levels < 350 ng/dL were randomized to one of three groups: 5 g transdermal testosterone gel (TT) (N = 16), anastrozole (AI) 1 mg (N = 14) or placebo daily (N = 13) for 12 months. Outcomes were assessed at baseline, 3, 6, and 12 months. Both TT and AI increased serum TT levels (> 500 ng/dL, p < 0.05) compared to baseline; T values remained stable throughout the duration of the trial. At 12 months, TT improved the primary outcome of lumbar spine BMD (p < 0.01). Both interventions improved knee strength at 12 months compared to baseline (p < 0.05) while lean body mass significantly increased only in the AI group at 6 and 12 months (1.49 +/- 0.38 kg, p < 0.01; 1.24 +/- 0.39 kg, p < 0.05, respectively) compared to baseline. Interestingly, TT improved fast gait speed at 3 and 12 months (p < 0.01, p < 0.05, respectively). In summary, this proof-of-concept study confirms that aromatization of T is required for maintaining BMD in older men with low-T levels. The trial also uncovered the novel finding that aromatization of T is required for improvement in fast gait speed, an observation that needs to be verified in future studies. C1 [Dias, J. P.; Melvin, D.; Carlson, O.; Egan, J. M.] NIA, Clin Invest Lab, Baltimore, MD 21225 USA. [Basaria, S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Sect Mens Hlth Aging & Metab, Boston, MA 02115 USA. [Simonsick, E. M.; Shardell, M. D.; Ferrucci, L.; Chia, C. W.] NIA, Translat Gerontol Branch, Baltimore, MD 21225 USA. RP Chia, CW (reprint author), NIA, Clin Invest Lab, Baltimore, MD 21225 USA.; Basaria, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Sect Mens Hlth Aging & Metab, Boston, MA 02115 USA. EM chiac@grc.nia.nih.gov; sbasaria@partners.org FU Intramural Research Program of the NIH, National Institute on Aging FX This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. Authors are most grateful to Dr. Jeffrey Metter for his advice and to the NIH Fellows Editorial Board. NR 40 TC 2 Z9 2 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-2919 EI 2047-2927 J9 ANDROLOGY-US JI Andrology PD JAN PY 2016 VL 4 IS 1 BP 33 EP 40 DI 10.1111/andr.12126 PG 8 WC Andrology SC Endocrinology & Metabolism GA DG9PA UT WOS:000372415000005 PM 26588809 ER PT J AU Miller, L Cunny, H Mylchreest, E AF Miller, L. Cunny, H. Mylchreest, E. TI Historical Control Data for Developmental Toxicity Parameters in Harlan Sprague-Dawley Rats SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-College-of-Toxicology (ACT) CY NOV 08-11, 2015 CL Summerlin, NV SP Amer Coll Toxicol C1 [Miller, L.; Mylchreest, E.] Southern Res, Birmingham, AL USA. [Cunny, H.] NIEHS, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 EI 1092-874X J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN-FEB PY 2016 VL 35 IS 1 SI SI MA P126 BP 57 EP 58 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA DG7XW UT WOS:000372298000024 ER PT J AU Park, JE AF Park, Jung E. TI The Problem of Functional SO JOURNAL OF MOVEMENT DISORDERS LA English DT Letter ID SYMPTOMS C1 [Park, Jung E.] NINDS, Human Motor Control Sect, NIH, Bldg 10,10 Ctr Dr Room 7D42, Bethesda, MD 20892 USA. RP Park, JE (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,10 Ctr Dr Room 7D42, Bethesda, MD 20892 USA. EM junge.park@nih.gov NR 5 TC 0 Z9 0 U1 1 U2 1 PU KOREAN MOVEMENT DISORDERS SOC PI SEOUL PA 2011 MAPO HANWHA OBELISK, 555, DOHWA-DONG, MAPO-GU, SEOUL, 04167, SOUTH KOREA SN 2005-940X EI 2093-4939 J9 J MOV DISORD JI J. Mov. Disord. PD JAN PY 2016 VL 9 IS 1 BP 53 EP 54 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA DH0VQ UT WOS:000372502600010 PM 26648180 ER PT J AU Trostchansky, A Quijano, C Yadav, H Kelley, EE Cassina, AM AF Trostchansky, Andres Quijano, Celia Yadav, Hariom Kelley, Eric E. Maria Cassina, Adriana TI Interplay between Oxidative Stress and Metabolism in Signalling and Disease SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Article C1 [Trostchansky, Andres; Quijano, Celia; Maria Cassina, Adriana] Univ Republica, Fac Med, Dept Bioquim, Montevideo 11800, Uruguay. [Trostchansky, Andres; Quijano, Celia; Maria Cassina, Adriana] Univ Republica, Fac Med, Ctr Free Rad & Biomed Res, Montevideo 11800, Uruguay. [Yadav, Hariom] NIDDK, NIH, Diabet Endocrinol & Obes Branch, Bethesda, MD 20892 USA. [Kelley, Eric E.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA. [Kelley, Eric E.] Univ Pittsburgh, Sch Med, Vasc Med Inst, Pittsburgh, PA 15261 USA. RP Trostchansky, A (reprint author), Univ Republica, Fac Med, Dept Bioquim, Montevideo 11800, Uruguay.; Trostchansky, A (reprint author), Univ Republica, Fac Med, Ctr Free Rad & Biomed Res, Montevideo 11800, Uruguay. EM trocha@fmed.edu.uy OI Yadav, Hariom/0000-0003-4504-1597 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1942-0900 EI 1942-0994 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2016 AR 3274296 DI 10.1155/2016/3274296 PG 2 WC Cell Biology SC Cell Biology GA DH2UJ UT WOS:000372641800001 ER PT J AU Glastonbury, CM Bhosale, PR Choyke, PL D'Orsi, CJ Erasmus, JJ Gill, RR Mukherji, SK Panicek, DM Schwartz, LH Subramaniam, RM Sullivan, DC AF Glastonbury, Christine M. Bhosale, Priya R. Choyke, Peter L. D'Orsi, Carl J. Erasmus, Jeremy J. Gill, Ritu R. Mukherji, Suresh K. Panicek, David M. Schwartz, Lawrence H. Subramaniam, Rathan M. Sullivan, Daniel C. TI Do Radiologists Have Stage Fright? Tumor Staging and How We Can Add Value to the Care of Patients with Cancer SO RADIOLOGY LA English DT Editorial Material C1 [Glastonbury, Christine M.] Univ Calif San Francisco, Dept Radiol, 505 Parnassus Ave, San Francisco, CA 94143 USA. [Bhosale, Priya R.; Erasmus, Jeremy J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Choyke, Peter L.] NCI, Bethesda, MD 20892 USA. [D'Orsi, Carl J.] Emory Univ Hosp, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. [Gill, Ritu R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Mukherji, Suresh K.] Michigan State Univ, E Lansing, MI 48824 USA. [Panicek, David M.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Schwartz, Lawrence H.] Columbia Univ, Med Ctr, New York, NY USA. [Subramaniam, Rathan M.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Sullivan, Daniel C.] Duke Univ, Med Ctr, Durham, NC USA. RP Glastonbury, CM (reprint author), Univ Calif San Francisco, Dept Radiol, 505 Parnassus Ave, San Francisco, CA 94143 USA. EM christine.glastonbury@ucsf.edu OI Panicek, David/0000-0003-0302-174X NR 3 TC 5 Z9 5 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2016 VL 278 IS 1 BP 11 EP 12 DI 10.1148/radiol.2015151563 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DH1BN UT WOS:000372519500003 PM 26690989 ER PT J AU Burns, JE Yao, JH Munoz, H Summers, RM AF Burns, Joseph E. Yao, Jianhua Munoz, Hector Summers, Ronald M. TI Automated Detection, Localization, and Classification of Traumatic Vertebral Body Fractures in the Thoracic and Lumbar Spine at CT SO RADIOLOGY LA English DT Article ID SUPPORT VECTOR MACHINES; THORACOLUMBAR INJURY CLASSIFICATION; SYSTEM; RECOGNITION; MORPHOMETRY AB Purpose: To design and validate a fully automated computer system for the detection and anatomic localization of traumatic thoracic and lumbar vertebral body fractures at computed tomography (CT). Materials and Methods: This retrospective study was HIPAA compliant. Institutional review board approval was obtained, and informed consent was waived. CT examinations in 104 patients (mean age, 34.4 years; range, 14-88 years; 32 women, 72 men), consisting of 94 examinations with positive findings for fractures (59 with vertebral body fractures) and 10 control examinations (without vertebral fractures), were performed. There were 141 thoracic and lumbar vertebral body fractures in the case set. The locations of fractures were marked and classified by a radiologist according to Denis column involvement. The CT data set was divided into training and testing subsets (37 and 67 subsets, respectively) for analysis by means of prototype software for fully automated spinal segmentation and fracture detection. Free-response receiver operating characteristic analysis was performed. Results: Training set sensitivity for detection and localization of fractures within each vertebra was 0.82 (28 of 34 findings; 95% confidence interval [CI]: 0.68, 0.90), with a false-positive rate of 2.5 findings per patient. The sensitivity for fracture localization to the correct vertebra was 0.88 (23 of 26 findings; 95% CI: 0.72, 0.96), with a false-positive rate of 1.3. Testing set sensitivity for the detection and localization of fractures within each vertebra was 0.81 (87 of 107 findings; 95% CI: 0.75, 0.87), with a false-positive rate of 2.7. The sensitivity for fracture localization to the correct vertebra was 0.92 (55 of 60 findings; 95% CI: 0.79, 0.94), with a false-positive rate of 1.6. The most common cause of false-positive findings was nutrient foramina (106 of 272 findings [39%]). Conclusion: The fully automated computer system detects and anatomically localizes vertebral body fractures in the thoracic and lumbar spine on CT images with a high sensitivity and a low false-positive rate. (C) RSNA, 2015 C1 [Burns, Joseph E.] Univ Calif Irvine, Dept Radiol Sci, Orange, CA 92668 USA. [Yao, Jianhua; Munoz, Hector; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Detect Lab, Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,Bldg 10,1C224,MSC1182, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Detect Lab, Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,Bldg 10,1C224,MSC1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU National Institutes of Health [1Z01 CL040004, ZIE CL090017-04] FX This research was supported by the National Institutes of Health (grants 1Z01 CL040004 and ZIE CL090017-04). NR 37 TC 2 Z9 2 U1 1 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2016 VL 278 IS 1 BP 64 EP 73 DI 10.1148/radiol.2015142346 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DH1BN UT WOS:000372519500007 PM 26172532 ER PT J AU Parsons, VV Gardner, K Patel, R Thein, SL AF Parsons, V. van Hamel Gardner, K. Patel, R. Thein, S. L. TI Venous thromboembolism in adults with sickle cell disease: experience of a single centre in the UK SO ANNALS OF HEMATOLOGY LA English DT Article DE Sickle cell disease; Venous thromboembolism; Deep vein thrombosis; Pulmonary embolism ID PULMONARY-EMBOLISM; POPULATION; THROMBOSIS; ANEMIA; COHORT AB Venous thromboembolism (VTE) is a recognised complication of sickle cell disease (SCD), long considered to be a hypercoagulable state. While there is a good understanding of arterial thrombosis in SCD, the nature of VTE in SCD is less well-characterised. In this retrospective cohort study, we found that the incidence of VTE in our patient cohort was higher than in the non-SCD black population; patients of all SCD genotypes with VTE had significantly elevated steady-state platelet counts compared to those without. Recent hospitalisation (typically with acute sickle pain) was the commonest precipitating risk factor. These findings suggest consideration of longer VTE prophylaxis for acute hospital admissions in SCD. C1 [Parsons, V. van Hamel; Gardner, K.; Thein, S. L.] Kings Coll Hosp NHS Fdn Trust, Dept Haematol Med, London SE5 9RS, England. [Gardner, K.; Thein, S. L.] Kings Coll London, Fac Life Sci & Med, Mol Haematol, London SE5 9NU, England. [Patel, R.] Kings Coll Hosp NHS Fdn Trust, Kings Thrombosis Ctr, London, England. [Thein, S. L.] NIH, Sickle Cell Branch, Natl Heart Lung & Blood Inst, Bldg 10 CRC 5E-5142,10 Ctr Dr, Bethesda, MD 20892 USA. RP Thein, SL (reprint author), Kings Coll Hosp NHS Fdn Trust, Dept Haematol Med, London SE5 9RS, England.; Thein, SL (reprint author), Kings Coll London, Fac Life Sci & Med, Mol Haematol, London SE5 9NU, England.; Thein, SL (reprint author), NIH, Sickle Cell Branch, Natl Heart Lung & Blood Inst, Bldg 10 CRC 5E-5142,10 Ctr Dr, Bethesda, MD 20892 USA. EM sl.thein@kcl.ac.uk NR 17 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-5555 EI 1432-0584 J9 ANN HEMATOL JI Ann. Hematol. PD JAN PY 2016 VL 95 IS 2 BP 227 EP 232 DI 10.1007/s00277-015-2531-8 PG 6 WC Hematology SC Hematology GA DF8JS UT WOS:000371604500007 ER PT J AU Sanchez-Paulete, AR Cueto, FJ Martinez-Lopez, M Labiano, S Morales-Kastresana, A Rodriguez-Ruiz, ME Jure-Kunkel, M Azpilikueta, A Aznar, MA Quetglas, JI Sancho, D Melero, I AF Sanchez-Paulete, Alfonso R. Cueto, Francisco J. Martinez-Lopez, Maria Labiano, Sara Morales-Kastresana, Aizea Rodriguez-Ruiz, Maria E. Jure-Kunkel, Maria Azpilikueta, Arantza Angela Aznar, M. Quetglas, Jose I. Sancho, David Melero, Ignacio TI Cancer Immunotherapy with Immunomodulatory Anti-CD137 and Anti-PD-1 Monoclonal Antibodies Requires BATF3-Dependent Dendritic Cells SO CANCER DISCOVERY LA English DT Article ID ANTIGEN-PRESENTING CELLS; ANTITUMOR IMMUNITY; CROSS-PRESENTATION; CHEMOTHERAPY; COMBINATION; RESPONSES; REVEALS; TUMORS; 4-1BB; IL-12 AB Weak and ineffective antitumor cytotoxic T lymphocyte (CTL) responses can be rescued by immunomodulatory mAbs targeting PD-1 or CD137. Using Batf3(-/-) mice, which are defective for cross-presentation of cell-associated antigens, we show that BATF3-dependent dendritic cells (DC) are essential for the response to therapy with anti-CD137 or anti-PD-1 mAbs. Batf3(-/-) mice failed to prime an endogenous CTL-mediated immune response toward tumor-associated antigens, including neoantigens. As a result, the immunomodulatory mAbs could not amplify any therapeutically functional immune response in these mice. Moreover, administration of systemic sFLT3L and local poly-ICLC enhanced DC-mediated cross-priming and synergized with anti-CD137-and anti-PD-1-mediated immunostimulation in tumor therapy against B16-ovalbumin-derived melanomas, whereas this function was lost in Batf3(-/-) mice. These experiments show that cross-priming of tumor antigens by FLT3L-and BATF3-dependent DCs is crucial to the efficacy of immunostimulatory mAbs and represents a very attractive point of intervention to enhance their clinical antitumor effects. SIGNIFICANCE: Immunotherapy with immunostimulatory mAbs is currently achieving durable clinical responses in different types of cancer. We show that cross-priming of tumor antigens by BATF3-dependent DCs is a key limiting factor that can be exploited to enhance the antitumor effi cacy of anti-PD-1 and anti-CD137 immunostimulatory mAbs. (C) 2015 AACR. C1 [Sanchez-Paulete, Alfonso R.; Labiano, Sara; Morales-Kastresana, Aizea; Azpilikueta, Arantza; Angela Aznar, M.; Quetglas, Jose I.; Melero, Ignacio] Univ Navarra, Div Immunol & Immunotherapy, Ctr Appl Med Res CIMA, E-31080 Pamplona, Spain. [Sanchez-Paulete, Alfonso R.; Labiano, Sara; Morales-Kastresana, Aizea; Rodriguez-Ruiz, Maria E.; Azpilikueta, Arantza; Angela Aznar, M.; Quetglas, Jose I.; Melero, Ignacio] Inst Invest Sanitaria Navarra IdISNA, Pamplona 31008, Spain. [Cueto, Francisco J.; Martinez-Lopez, Maria; Sancho, David] Ctr Nacl Invest Cardiovasc Carlos III CNIC, Melchor Fernandez Almagro 3, Madrid 28029, Spain. [Cueto, Francisco J.] Univ Autonoma Madrid, Fac Med, Dept Biochem, Madrid, Spain. [Rodriguez-Ruiz, Maria E.; Melero, Ignacio] Univ Navarra, Univ Clin, E-31080 Pamplona, Spain. [Jure-Kunkel, Maria] Bristol Myers Squibb Co, Princeton, NJ USA. [Morales-Kastresana, Aizea] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Sancho, D (reprint author), Ctr Nacl Invest Cardiovasc Carlos III CNIC, Melchor Fernandez Almagro 3, Madrid 28029, Spain.; Melero, I (reprint author), Univ Navarra, Av Pio 12,55, Navarra 31008, Spain.; Melero, I (reprint author), Inst Invest Sanitaria Navarra IdISNA, Av Pio 12,55, Navarra 31008, Spain. EM dsancho@cnic.es; imelero@unav.es RI Sancho, David/D-3433-2009; OI Sancho, David/0000-0003-2890-3984; MELERO BERMEJO, IGNACIO/0000-0002-1360-348X; Rodriguez Sanchez-Paulete, Alfonso/0000-0001-7475-1913 FU MICINN [SAF2008-03294, SAF2011-22831]; Departamento de salud del Gobierno de Navarra, Redes tematicas de investigacion cooperativa RETIC [RD06/0020/0065]; European commission; CNIC; Spanish Ministry of Economy and Competitiveness [SAF-2013-42920R]; European Research Council (ERC) [ERC-2010-StG 260414]; Spanish Ministry of Economy and Competitiveness; Pro-CNIC Foundation; European Commission [635122-PROCROP H2020] FX Work at the I. Melero lab is funded by MICINN (SAF2008-03294 and SAF2011-22831), Departamento de salud del Gobierno de Navarra, Redes tematicas de investigacion cooperativa RETIC (RD06/0020/0065), and the European commission 7th framework program (ENCITE and IACT). Work in the D. Sancho laboratory is funded by the CNIC and grants from the Spanish Ministry of Economy and Competitiveness (SAF-2013-42920R) and the European Research Council (ERC Starting Independent Researcher Grant 2010, ERC-2010-StG 260414). The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and the Pro-CNIC Foundation. I. Melero and D. Sancho are funded by the European Commission (635122-PROCROP H2020). NR 29 TC 24 Z9 24 U1 5 U2 12 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 JAN PY 2016 VL 6 IS 1 BP 71 EP 79 DI 10.1158/2159-8290.CD-15-0510 PG 9 WC Oncology SC Oncology GA DG8HA UT WOS:000372322500025 PM 26493961 ER PT J AU Mahale, P Yanik, EL Engels, EA AF Mahale, Parag Yanik, Elizabeth L. Engels, Eric A. TI Herpes Zoster and Risk of Cancer in the Elderly US Population SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; COMMUNITY-ACQUIRED INFECTIONS; HUMAN-IMMUNODEFICIENCY-VIRUS; SOLID-ORGAN TRANSPLANTATION; SOFT-TISSUE SARCOMA; B-CELL LYMPHOMA; UNITED-STATES; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; MULTIPLE-MYELOMA AB Background: Herpes zoster (HZ) arises in older people due to age-related decline in immunity. We assessed whether HZ, as a marker of immune suppression, is associated with increased cancer risk. Methods: We conducted a case-control study in U.S. adults with ages >= 65 years using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Cases (n = 1,108,986) were people with first cancers identified in cancer registries (1992-2005). Controls (n = 100,000) were cancer-free individuals frequency matched to cases on age, sex, and year of selection. We identified HZ diagnosis using Medicare claims. Logistic regression models were constructed to determine adjusted associations between cancer and HZ. Results: HZ prevalence was modestly higher in cases than controls (1.4% vs. 1.2%). We identified significant associations between HZ and oral cavity/pharyngeal [adjusted OR (aOR) = 1.21], colon (aOR = 1.10), lung (aOR = 1.11), and non-melanoma skin (aOR = 1.46) cancers; myeloma (aOR = 1.38); diffuse large B-cell lymphoma (aOR = 1.30); lymphoplasmacytic lymphoma (aOR = 1.99); and chronic lymphocytic leukemia/small lymphocytic lymphoma (aOR = 1.55). Among solid cancers, HZ was mostly associated with regional and/or distant stage tumors. Associations were strongest when HZ was diagnosed 13 to 35 months before cancer diagnosis/selection; they were significant for some cancers in the 36 to 59 months period, and 60+ months for lymphoplasmacytic lymphoma (OR = 1.99). Conclusion: HZ is associated with modestly increased risk of a few cancers, particularly hematologic malignancies. Associations were strongest at short latency intervals for many cancers, and for regional/distant stages among solid cancers, perhaps reflecting reverse causality. Impact: Age-related immune decline does not play a major role in cancer development in older people, but it may be important for some lymphomas. (C) 2015 AACR. C1 [Mahale, Parag; Yanik, Elizabeth L.; Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Mahale, Parag] Univ Texas Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Houston, TX USA. RP Engels, EA (reprint author), NCI, 9609 Med Ctr Dr,Room 6E226, Bethesda, MD 20892 USA. EM engelse@exchange.nih.gov FU Intramural Research Program of the NCI at the NIH FX E.A. Engels was supported by the Intramural Research Program of the NCI at the NIH. NR 54 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2016 VL 25 IS 1 BP 28 EP 35 DI 10.1158/1055-9965.EPI-15-1033 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DG6DC UT WOS:000372171400004 PM 26578536 ER PT J AU Gage, JC Hunt, WC Schiffman, M Katki, HA Cheung, LC Cuzick, J Myers, O Castle, PE Wheeler, CM AF Gage, Julia C. Hunt, William C. Schiffman, Mark Katki, Hormuzd A. Cheung, Li C. Cuzick, Jack Myers, Orrin Castle, Philip E. Wheeler, Cosette M. CA New Mexico HPV Pap Registry Steeri TI Risk Stratification Using Human Papillomavirus Testing among Women with Equivocally Abnormal Cytology: Results from a State-Wide Surveillance Program SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CERVICAL-CANCER; UNITED-STATES; UNDETERMINED SIGNIFICANCE; RANDOMIZED-TRIAL; SQUAMOUS-CELLS; 5-YEAR RISKS; MANAGEMENT; HPV; PERFORMANCE; GUIDELINES AB Background: Clinical guidelines for cervical cancer screening have incorporated comparative risks of cervical intraepithelial neoplasia grade 3 or cancer (CIN3(+)) for various screening outcomes to determine management. Few cohorts are large enough to distinguish CIN3(+) risks among women with minor abnormalities versus negative cytology because of low incidence. The New Mexico Human Papillomavirus (HPV) Pap Registry offers a unique opportunity to evaluate cervical cancer screening in a diverse population across a broad-spectrum of health service delivery. Methods: Kaplan-Meier and logistic-Weibull survival models were used to estimate cumulative risks of CIN3(+) among women ages 21 to 64 who were screened in New Mexico between 2007 and 2011 with negative, equivocal or mildly abnormal cytology, that is, atypical squamous cells of undetermined significance (ASC-US; with or without HPV triage), or low-grade squamous intraepithelial lesions (LSIL). Results: We identified 452,045 women meeting the selection criteria. The 3-year CIN3(+) risks for women with negative, ASC-US, and LSIL cytology were 0.30%, 2.6%, and 5.2%, respectively. HPV triage of ASC-US stratified 3-year CIN3(+) risks were 0.72% for HPV-negative and 7.7% for HPV-positive. Risks tended to decline after age 30 for all screening results. Conclusions: In this state-wide population-based cohort, cytology and HPV triage of ASC-US stratified women's CIN3(+) risk into similar patterns observed previously, suggesting the validity of screening guidelines for diverse populations in the United States. Absolute risk estimates should be compared across other large populations. Impact: Strategies for HPV triage of ASC-US derived from clinical trials are upheld in large clinical practice settings and across diverse screening populations in the United States. (C) 2015 AACR. C1 [Gage, Julia C.; Schiffman, Mark; Katki, Hormuzd A.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Hunt, William C.; Wheeler, Cosette M.] Univ New Mexico, Hlth Sci Ctr, Dept Pathol, Albuquerque, NM 87131 USA. [Cheung, Li C.] Informat Management Serv Inc, Calverton, MD USA. [Cuzick, Jack] Queen Mary Univ London, Wolfson Inst Prevent Med, Ctr Canc Prevent, Charterhouse Sq, London, England. [Myers, Orrin] Univ New Mexico, Hlth Sci Ctr, Dept Internal Med, Albuquerque, NM 87131 USA. [Castle, Philip E.] Albert Einstein Coll Med, New York, NY USA. RP Wheeler, CM (reprint author), Univ New Mexico, Hlth Sci Ctr, HOPE,1816 Sigma Chi Rd NE,MSC02-1670, Albuquerque, NM 87131 USA. EM cwheeler@salud.unm.edu OI Cheung, Li/0000-0003-1625-4331 FU U.S. National Cancer Institute-funded Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium; Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services; Qiagen; Roche; Genprobe/Hologic; Abbott; Becton Dickinson; Cepheid; Genera; Travogene; University of New Mexico from Merck and Co., Inc.; GlaxoSmithKline FX This effort was supported by U54CA164336 (to C.M. Wheeler) from the U.S. National Cancer Institute-funded Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium and in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. The overall aim of PROSPR is to conduct multisite, coordinated, transdisciplinary research to evaluate and improve cancer screening processes. J. Cuzick has received research funding and reagents from Qiagen, Roche, Genprobe/Hologic, Abbott, Becton Dickinson, Cepheid, Genera, and Travogene. C.M. Wheeler has received funding through the University of New Mexico from Merck and Co., Inc. and GlaxoSmithKline for HPV vaccine studies and equipment and reagents from Roche Molecular Systems for HPV genotyping. NR 22 TC 2 Z9 2 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2016 VL 25 IS 1 BP 36 EP 42 DI 10.1158/1055-9965.EPI-15-0669 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DG6DC UT WOS:000372171400005 PM 26518316 ER PT J AU Sun, XZ Nichols, HB Tse, CK Bell, MB Robinson, WR Sherman, ME Olshan, AF Troester, MA AF Sun, Xuezheng Nichols, Hazel B. Tse, Chiu-Kit Bell, Mary B. Robinson, Whitney R. Sherman, Mark E. Olshan, Andrew F. Troester, Melissa A. TI Association of Parity and Time since Last Birth with Breast Cancer Prognosis by Intrinsic Subtype SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID REPRODUCTIVE FACTORS; RISK-FACTORS; TERM PREGNANCY; MAMMARY-GLAND; YOUNG-WOMEN; SURVIVAL; AGE; MORTALITY; CHILDBIRTH; EPIDEMIOLOGY AB Background: Parity and time since last birth influence breast cancer risk and vary by intrinsic tumor subtype, but the independent effects of these factors on prognosis have received limited attention. Methods: Study participants were 1,140 invasive breast cancer patients from phases I and II of the population-based Carolina Breast Cancer Study, with tissue blocks available for subtyping using immunohistochemical markers. Breast cancer risk factors, including pregnancy history, were collected via in-person interviews administered shortly after diagnosis. Vital status was determined using the National Death Index. The association of parity and birth recency with breast cancer-specific and overall survival was assessed using Cox proportional hazards models. Results: During follow-up (median = 13.5 years), 450 patients died, 61% due to breast cancer (n = 276). High parity (3+ births) and recent birth (<5 years before diagnosis) were positively associated with breast cancer-specific mortality, independent of age, race, and selected socioeconomic factors [parity, reference = nulliparous, adjusted HR = 1.76; 95% confidence interval (CI) = 1.13-2.73; birth recency, reference = 10+ years, adjusted HR = 1.29; 95% CI, 0.79-2.11]. The associations were stronger among patients with luminal tumors and those surviving longer than 5 years. Conclusions: Parity and recent birth are associated with worse survival among breast cancer patients, particularly among luminal breast cancers and long-term survivors. Impact: The biologic effects of parity and birth recency may extend from etiology to tumor promotion and progression. (C) 2015 AACR. C1 [Sun, Xuezheng; Nichols, Hazel B.; Tse, Chiu-Kit; Robinson, Whitney R.; Olshan, Andrew F.; Troester, Melissa A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Nichols, Hazel B.; Bell, Mary B.; Olshan, Andrew F.; Troester, Melissa A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Sherman, Mark E.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Sherman, Mark E.] NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Troester, MA (reprint author), Univ N Carolina, 135 Dauer Dr, Chapel Hill, NC 27599 USA. EM troester@unc.edu FU NCI [U01-ES019472, P50CA058223, K01CA172717]; Development Award from the University of North Carolina at Chapel Hill; University Cancer Research Fund from the University of North Carolina at Chapel Hill FX This work was supported by grants from the NCI (U01-ES019472 and P50CA058223; to M.A. Troester) and by the Development Award and the University Cancer Research Fund from the University of North Carolina at Chapel Hill (to M.A. Troester). This work was also supported (in part) by a grant from the NCI (K01CA172717; to W.R. Robinson). NR 53 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2016 VL 25 IS 1 BP 60 EP 67 DI 10.1158/1055-9965.EPI-15-0864 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DG6DC UT WOS:000372171400008 PM 26545404 ER PT J AU Arnold, M Colquhoun, A Cook, MB Ferlay, J Forman, D Soerjomataram, I AF Arnold, Melina Colquhoun, Amy Cook, Michael B. Ferlay, Jacques Forman, David Soerjomataram, Isabelle TI Obesity and the Incidence of Upper Gastrointestinal Cancers: An Ecological Approach to Examine Differences across Age and Sex SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BODY-MASS INDEX; INTERNATIONAL BEACON CONSORTIUM; HELICOBACTER-PYLORI; BARRETTS-ESOPHAGUS; POOLED ANALYSIS; GASTRIC-CANCER; UNITED-STATES; ESOPHAGOGASTRIC JUNCTION; MALE PREDOMINANCE; ADENOCARCINOMA AB Background: Esophageal and gastric cancers differ in their epidemiology but have several risk factors in common. The aim of this study was to assess age and sex differences in the burden of esophageal and gastric cancers in the context of the global obesity epidemic. Methods: Data from 50 countries were obtained from Cancer Incidence in Five Continents Volume X and GLOBOCAN 2012. Age-specific and age-standardized incidence rates of esophageal adenocarcinoma and squamous cell carcinoma (ESCC), as well as cardia (CGC) and noncardia (NCGC) gastric cancer, were estimated. Countries were grouped and analyzed according to their obesity prevalence. Results: A gradient across quartiles of obesity prevalence was found for esophageal adenocarcinoma, with the highest incidence rates in high prevalence countries (ASR 3.0 vs. 0.8 per 100,000 in highest vs. lowest obesity quartiles, males). In contrast, for ESCC as well as for CGC and NCGC the reverse was true, with the highest rates observed in countries with the lowest obesity prevalence (ESCC, 2.2 vs. 11.5; CGC, 2.8 vs. 7.8; NCGC, 3.9 vs. 17.4 in highest vs. lowest obesity quartiles, males). Although for esophageal adenocarcinoma, sex and age differences in incidence were most pronounced in countries with a high prevalence of obesity, these differences were much smaller for the other cancer sites assessed. Conclusions: Variation in obesity prevalence may partly explain age and sex differences in the incidence of esophageal adenocarcinomas. Impact: Ecologic studies can help assess relationships between risk factors and cancer, and generate new hypotheses that may be pursued through more directed research. (C) 2015 AACR. C1 [Arnold, Melina; Ferlay, Jacques; Forman, David; Soerjomataram, Isabelle] Int Agcy Res Canc, Sect Canc Surveillance, F-69008 Lyon, France. [Colquhoun, Amy] Univ Alberta, Sch Publ Hlth, Edmonton, AB, Canada. [Cook, Michael B.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. RP Arnold, M (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69008 Lyon, France. EM arnoldm@fellows.iarc.fr RI Cook, Michael/A-5641-2009 OI Cook, Michael/0000-0002-0533-7302 FU Vanier Canada Graduate Scholarship; Michael Smith Foreign Study Supplement FX A. Colquhoun is supported by a Vanier Canada Graduate Scholarship and a Michael Smith Foreign Study Supplement. NR 54 TC 2 Z9 2 U1 2 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 JAN PY 2016 VL 25 IS 1 BP 90 EP 97 DI 10.1158/1055-9965.EPI-15-0753 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DG6DC UT WOS:000372171400012 PM 26494763 ER PT J AU Schairer, C Fuhrman, BJ Boyd-Morin, J Genkinger, JM Gail, MH Hoover, RN Ziegler, RG AF Schairer, Catherine Fuhrman, Barbara J. Boyd-Morin, Jennifer Genkinger, Jeanine M. Gail, Mitchell H. Hoover, Robert N. Ziegler, Regina G. TI Quantifying the Role of Circulating Unconjugated Estradiol in Mediating the Body Mass Index-Breast Cancer Association SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PROGESTERONE-RECEPTOR STATUS; POSTMENOPAUSAL WOMEN; WEIGHT CHANGE; RISK; ESTROGEN; OBESITY; NUTRITION; INSULIN; METABOLISM; HORMONES AB Background: Higher body mass index (BMI) and circulating estrogen levels each increase postmenopausal breast cancer risk, particularly estrogen receptor-positive (ER+) tumors. Higher BMI also increases estrogen production. Methods: We estimated the proportion of the BMI-ER+ breast cancer association mediated through estrogen in a case-control study nested within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Participants included 143 women with invasive ER+ breast cancer and 268 matched controls, all postmenopausal and never having used hormone therapy at baseline. We used liquid chromatography-tandem mass spectrometry to measure 15 estrogens and estrogen metabolites in baseline serum. We calculated BMI from self-reported height and weight at baseline. We estimated the mediating effect of unconjugated estradiol on the BMI-ER+ breast cancer association using Aalen additive hazards and Cox regression models. Results: All estrogens and estrogen metabolites were statistically significantly correlated with BMI, with unconjugated estradiol most strongly correlated [Pearson correlation (r) = 0.45]. Approximately 7% to 10% of the effect of overweight, 12% to 15% of the effect of obesity, and 19% to 20% of the effect of a 5 kg/m(2) BMI increase on ER+ breast cancer risk was mediated through unconjugated estradiol. The BMI-breast cancer association, once adjusted for unconjugated estradiol, was not modified by further adjustment for two metabolic ratios statistically significantly associated with both breast cancer and BMI. Conclusion: Circulating unconjugated estradiol levels partially mediate the BMI-breast cancer association, but other potentially important estrogen mediators (e.g., bioavailable estradiol) were not evaluated. Impact: Further research is required to identify mechanisms underlying the BMI-breast cancer association. (C) 2015 AACR. C1 [Schairer, Catherine; Gail, Mitchell H.; Hoover, Robert N.; Ziegler, Regina G.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Fuhrman, Barbara J.] Univ Arkansas Med Sci, Dept Epidemiol, Coll Publ Hlth, Little Rock, AR 72205 USA. [Boyd-Morin, Jennifer] Informat Management Serv Inc, Silver Spring, MD USA. [Genkinger, Jeanine M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Genkinger, Jeanine M.] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA. RP Schairer, C (reprint author), NCI, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM schairec@exchange.nih.gov FU Intramural Research Programs of the Division of Cancer Epidemiology and Genetics of the NCI, NIH; Division of Cancer Prevention of the NCI, NIH; NCI, NIH [HHSN261200800001E] FX This work was supported by the Intramural Research Programs of the Division of Cancer Epidemiology and Genetics of the NCI, NIH; the Division of Cancer Prevention of the NCI, NIH; and contract HHSN261200800001E to Leidos, Inc., from NCI, NIH. NR 31 TC 4 Z9 5 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2016 VL 25 IS 1 BP 105 EP 113 DI 10.1158/1055-9965.EPI-15-0687 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DG6DC UT WOS:000372171400014 PM 26637268 ER PT J AU Meulepas, JM Ronckers, CM Merks, J Weijerman, ME Lubin, JH Hauptmann, M AF Meulepas, Johanna M. Ronckers, Cecile M. Merks, Johannes Weijerman, Michel E. Lubin, Jay H. Hauptmann, Michael TI Confounding of the Association between Radiation Exposure from CT Scans and Risk of Leukemia and Brain Tumors by Cancer Susceptibility Syndromes (Retracted article. See vol. 25, pg. 1192, 2016) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article; Retracted Publication ID LARGE-SCALE COHORT; NIJMEGEN BREAKAGE SYNDROME; LHERMITTE-DUCLOS-DISEASE; CELL CARCINOMA SYNDROME; SILVER-RUSSELL-SYNDROME; HIPPEL-LINDAU-DISEASE; STURGE-WEBER-SYNDROME; LI-FRAUMENI SYNDROME; OF-THE-LITERATURE; GENOTYPE-PHENOTYPE CORRELATIONS AB Background: Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). These syndromes might be confounders because they are associated with an increased cancer risk and may increase the likelihood of CT scans performed in children. Methods: We identify CSS predisposing to leukemia and brain tumors through a systematic literature search and summarize prevalence and risk estimates. Because there is virtually no empirical evidence in published literature on patterns of CT use for most types of CSS, we estimate confounding bias of relative risks (RR) for categories of radiation exposure based on expert opinion about the current and previous patterns of CT scans among CSS patients. Results: We estimate that radiation-related RRs for leukemia are not meaningfully confounded by Down syndrome, Noonan syndrome, or other CSS. In contrast, RRs for brain tumors may be overestimated due to confounding by tuberous sclerosis complex (TSC) while von Hippel-Lindau disease, neurofibromatosis type 1, or other CSS do not meaningfully confound. Empirical data on the use of CT scans among CSS patients are urgently needed. Conclusions: Our assessment indicates that associations with leukemia reported in previous studies are unlikely to be substantially confounded by unmeasured CSS, whereas brain tumor risks might have been overestimated due to confounding by TSC. Impact: Future studies should identify TSC patients in order to avoid overestimation of brain tumor risks due to radiation exposure from CT scans. (C) 2015 AACR. C1 [Meulepas, Johanna M.; Hauptmann, Michael] Netherlands Canc Inst, Dept Epidemiol & Biostat, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands. [Ronckers, Cecile M.; Merks, Johannes] Emma Childrens Hosp, Acad Med Ctr, Dept Paediat Oncol, Amsterdam, Netherlands. [Weijerman, Michel E.] Vrije Univ Amsterdam, Dept Paediat, Med Ctr, Amsterdam, Netherlands. [Lubin, Jay H.] NIH, Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. RP Hauptmann, M (reprint author), Netherlands Canc Inst, Dept Epidemiol & Biostat, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands. EM m.hauptmann@nki.nl FU European Community Seventh Framework Programme [269912-EPI-CT]; Worldwide Cancer Research [12-1155]; Intramural Research Program of the NCI, NIH, Department of Health and Human Services; Dutch Cancer Society FX This work was supported by the European Community Seventh Framework Programme (grant number FP7/2007-2013) under Grant Agreement Number 269912-EPI-CT: "Epidemiological study to quantify risks for paediatric computerized tomography and to optimize doses" and by Worldwide Cancer Research formerly known as Association for International Cancer Research (AICR; grant number 12-1155). Dr. J.H. Lubin is supported by the Intramural Research Program of the NCI, NIH, Department of Health and Human Services. Dr. C.M. Ronckers is supported by the Dutch Cancer Society. NR 148 TC 1 Z9 1 U1 3 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 JAN PY 2016 VL 25 IS 1 BP 114 EP 126 DI 10.1158/1055-9965.EPI-15-0636 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DG6DC UT WOS:000372171400015 PM 26598533 ER PT J AU Howlader, N Morton, LM Feuer, EJ Besson, C Engels, EA AF Howlader, Nadia Morton, Lindsay M. Feuer, Eric J. Besson, Caroline Engels, Eric A. TI Contributions of Subtypes of Non-Hodgkin Lymphoma to Mortality Trends SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COLORECTAL-CANCER MORTALITY; POPULATION-BASED ANALYSIS; ACUTE MYELOID-LEUKEMIA; B-CELL LYMPHOMA; UNITED-STATES; FOLLICULAR LYMPHOMA; EPIDEMIOLOGIC RESEARCH; CHANGING INCIDENCE; ELDERLY PATIENTS; PROSTATE-CANCER AB Background: Non-Hodgkin lymphoma (NHL) comprises distinct tumor subtypes. Although mortality from NHL overall has changed dramatically in the United States over time, little is known about trends for subtypes, because death certificates do not record this information. Methods: Using data from U.S. Surveillance, Epidemiology, and End Results (SEER) areas, we assessed NHL mortality rates and mapped NHL deaths to incident NHL cases in SEER cancer registries. This allowed us to evaluate population-level mortality trends attributed to specific NHL subtypes (incidence-based mortality; IBM). We also describe NHL incidence and survival after NHL diagnosis by calendar year. We used Joinpoint to identify years when IBM and incidence rate trends changed slope. Results: Overall NHL mortality rates increased during 1975-1997, peaking at 10.9 per 100,000 person-years, then decreased subsequently in 1997-2011. Overall IBM rates mirror this trend during 1990-2011. For B-cell NHL subtypes, IBM rates decreased beginning in the mid-1990s, with yearly declines of -3.0% for diffuse large B-cell lymphoma (DLBCL), -2.7% for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and -5.3% for follicular lymphoma. Incidence rates for these subtypes did not decrease until after 2003. Corresponding 5-year cancer-specific survival increased dramatically over time for DLBCL (from 37%-66%), CLL/SLL (69%-84%), and follicular lymphoma (69%-82%). IBM for peripheral T-cell lymphoma was flat during 2006-2011, although incidence increased. Conclusions: Mortality due to three common B-cell NHL subtypes has fallen over time in the United States. Impact: This decline reflects better survival after NHL diagnosis, likely from improved therapies, because the decline in NHL incidence occurred later. (C) 2015 AACR. C1 [Howlader, Nadia; Feuer, Eric J.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Howlader, Nadia] George Washington Univ, Dept Epidemiol & Biostat, Milken Inst Sch Publ Hlth, Washington, DC USA. [Morton, Lindsay M.; Besson, Caroline; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Besson, Caroline] Univ Paris 11, Fac Med Paris Sud, Le Kremlin Bicetre, France. RP Howlader, N (reprint author), NCI, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM howladern@mail.nih.gov OI Besson, Caroline/0000-0003-4364-7173 FU National Cancer Institute's Intramural Research Program in the Division of Cancer Epidemiology and Genetics; Surveillance Research Program in the Division of Cancer Control and Population Sciences FX This work was supported by the National Cancer Institute's Intramural Research Program in the Division of Cancer Epidemiology and Genetics and Surveillance Research Program in the Division of Cancer Control and Population Sciences. NR 53 TC 4 Z9 4 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2016 VL 25 IS 1 BP 174 EP 179 DI 10.1158/1055-9965.EPI-15-0921 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DG6DC UT WOS:000372171400022 PM 26472423 ER PT J AU Bei, JX Su, WH Ng, CC Yu, K Chin, YM Lou, PJ Hsu, WL McKay, JD Chen, CJ Chang, YS Chen, LZ Chen, MY Cui, Q Feng, FT Feng, QS Guo, YM Jia, WH Khoo, ASB Liu, WS Mo, HY Pua, KC Teo, SH Tse, KP Xia, YF Zhang, H Zhou, GQ Liu, JJ Zeng, YX Hildesheim, A AF Bei, Jin-Xin Su, Wen-Hui Ng, Ching-Ching Yu, Kai Chin, Yoon-Ming Lou, Pei-Jen Hsu, Wan-Lun McKay, James D. Chen, Chien-Jen Chang, Yu-Sun Chen, Li-Zhen Chen, Ming-Yuan Cui, Qian Feng, Fu-Tuo Feng, Qi-Shen Guo, Yun-Miao Jia, Wei-Hua Khoo, Alan Soo-Beng Liu, Wen-Sheng Mo, Hao-Yuan Pua, Kin-Choo Teo, Soo-Hwang Tse, Ka-Po Xia, Yun-Fei Zhang, Hongxin Zhou, Gang-Qiao Liu, Jian-Jun Zeng, Yi-Xin Hildesheim, Allan CA Int Nasopharyngeal Carcinoma NPC G TI A GWAS Meta-analysis and Replication Study Identifies a Novel Locus within CLPTM1L/TERT Associated with Nasopharyngeal Carcinoma in Individuals of Chinese Ancestry SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; RISK; TELOMERASE; SUSCEPTIBILITY; NPC AB Background: Genetic loci within the major histocompatibility complex (MHC) have been associated with nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated cancer, in several GWAS. Results outside this region have varied. Methods: We conducted a meta-analysis of four NPC GWAS among Chinese individuals (2,152 cases; 3,740 controls). Forty-three noteworthy findings outside the MHC region were identified and targeted for replication in a pooled analysis of four independent case-control studies across three regions in Asia (4,716 cases; 5,379 controls). A meta-analysis that combined results from the initial GWA and replication studies was performed. Results: In the combined meta-analysis, rs31489, located within the CLPTM1L/TERT region on chromosome 5p15.33, was strongly associated with NPC (OR = 0.81; P value 6.3 x 10(-13)). Our results also provide support for associations reported from published NPC GWAS-rs6774494 (P = 1.5 x 10(-12); located in the MECOM gene region), rs9510787 (P = 5.0 x 10(-10); located in the TNFRSF19 gene region), and rs1412829/rs4977756/rs1063192 (P = 2.8 x 10(-8), P = 7.0 x 10(-7), and P = 8.4 x 10(-7), respectively; located in the CDKN2A/B gene region). Conclusions: We have identified a novel association between genetic variation in the CLPTM1L/TERT region and NPC. Supporting our finding, rs31489 and other SNPs in this region have been reported to be associated with multiple cancer sites, candidate-based studies have reported associations between polymorphisms in this region and NPC, the TERT gene has been shown to be important for telomere maintenance and has been reported to be overexpressed in NPC, and an EBV protein expressed in NPC (LMP1) has been reported to modulate TERT expression/telomerase activity. Impact: Our finding suggests that factors involved in telomere length maintenance are involved in NPC pathogenesis. (C) 2015 AACR. C1 [Bei, Jin-Xin; Chen, Li-Zhen; Chen, Ming-Yuan; Cui, Qian; Feng, Fu-Tuo; Feng, Qi-Shen; Guo, Yun-Miao; Jia, Wei-Hua; Liu, Wen-Sheng; Mo, Hao-Yuan; Xia, Yun-Fei; Zeng, Yi-Xin] Sun Yat Sen Univ, Ctr Canc, Dept Expt Res, Guangzhou 510060, Guangdong, Peoples R China. [Bei, Jin-Xin; Chen, Li-Zhen; Chen, Ming-Yuan; Cui, Qian; Feng, Fu-Tuo; Feng, Qi-Shen; Guo, Yun-Miao; Jia, Wei-Hua; Liu, Wen-Sheng; Mo, Hao-Yuan; Xia, Yun-Fei; Zeng, Yi-Xin] State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China. [Bei, Jin-Xin; Chen, Li-Zhen; Chen, Ming-Yuan; Cui, Qian; Feng, Fu-Tuo; Feng, Qi-Shen; Guo, Yun-Miao; Jia, Wei-Hua; Liu, Wen-Sheng; Mo, Hao-Yuan; Xia, Yun-Fei; Zeng, Yi-Xin] Collaborat Innovat Ctr Canc Med, Guangzhou, Guangdong, Peoples R China. [Su, Wen-Hui] Chang Gung Univ, Coll Med, Grad Inst Biomed Sci, Dept Biomed Sci, Taoyuan, Taiwan. [Su, Wen-Hui] Chang Gung Univ, Chang Gung Mol Med Res Ctr, Taoyuan, Taiwan. [Ng, Ching-Ching; Chin, Yoon-Ming] Univ Malaya, Fac Sci, Inst Biol Sci, Kuala Lumpur, Malaysia. [Yu, Kai] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Lou, Pei-Jen] Natl Taiwan Univ Hosp, Dept Otolaryngol, Taipei, Taiwan. [Lou, Pei-Jen] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. [Hsu, Wan-Lun; Chen, Chien-Jen] Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10764, Taiwan. [Hsu, Wan-Lun; Chen, Chien-Jen] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan. [McKay, James D.] Int Agcy Res Canc, Genet Canc Susceptibil Grp, 150 Cours Albert Thomas, F-69372 Lyon, France. [Chang, Yu-Sun; Tse, Ka-Po] Chang Gung Univ, Chang Gung Mol Med Res Ctr, Taoyuan, Taiwan. [Chang, Yu-Sun; Tse, Ka-Po] Chang Gung Univ, Grad Inst Biomed Sci, Taoyuan, Taiwan. [Khoo, Alan Soo-Beng] Inst Med Res, Canc Res Ctr, Mol Pathol Unit, Kuala Lumpur 50588, Malaysia. [Pua, Kin-Choo] Hosp Pulau Pinang, Dept Otorhinolaryngol, George Town, Malaysia. [Teo, Soo-Hwang] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Selangor, Malaysia. [Zhang, Hongxin; Zhou, Gang-Qiao] Beijing Inst Radiat Med, Dept Genom & Prote, Beijing Proteome Res Ctr, Beijing, Peoples R China. [Liu, Jian-Jun] Genome Inst Singapore, 60 Biopolis St,Genome 02-01, Singapore 0201, Singapore. [Zeng, Yi-Xin] Peking Union Med Coll, Beijing 100021, Peoples R China. [Hildesheim, Allan] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Liu, JJ (reprint author), Genome Inst Singapore, 60 Biopolis St,Genome 02-01, Singapore 0201, Singapore.; Hildesheim, A (reprint author), NCI, 9609 Med Ctr Dr,Room 6-E102, Bethesda, MD 20892 USA.; Zeng, YX (reprint author), Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol Southern China, 651 Dong Feng Rd East, Guangzhou 510060, Guangdong, Peoples R China. EM liuj3@gis.a-star.edu.sg; zengyx@sysucc.org.cn; hildesha@mail.nih.gov RI Teo, Soo-hwang/H-2353-2014; NG, CHING CHING/B-9221-2010 FU National High Technology Research and Development Program of China (863) [2012AA02A501, 2012AA02A206]; Major State Basic Research Development Program of China (973) [2011CB504302]; National Natural Science Foundation of China [81222035, 81101544]; Pearl River Nova Program; Agency for Science, Technology, and Research of Singapore; Ministry of Education of Taiwan; Malaysian Ministry of Higher Education-High Impact Research [H-50001-A000023]; Intramural Research Program of the U.S. National Cancer Institute FX This work was supported by the National High Technology Research and Development Program of China (863; 2012AA02A501, 2012AA02A206; J.-X. Bei and Y. Zeng), the Major State Basic Research Development Program of China (973; 2011CB504302; to J.-X. Bei and Y. Zeng), the National Natural Science Foundation of China (81222035, 81101544; to J.-X. Bei and Y. Zeng), the Pearl River Nova Program and the Agency for Science, Technology, and Research of Singapore (to J.-X. Bei and J. Liu), the Ministry of Education of Taiwan, the Malaysian Ministry of Higher Education-High Impact Research (H-50001-A000023; to C. Ng and Y. Chin), and by the Intramural Research Program of the U.S. National Cancer Institute (to A. Hildesheim and K. Yu). NR 17 TC 5 Z9 5 U1 3 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2016 VL 25 IS 1 BP 188 EP 192 DI 10.1158/1055-9965.EPI-15-0144 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DG6DC UT WOS:000372171400024 PM 26545403 ER EF