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Found 37769 matches. Displaying 5781-5790
Nectow AR, Ekstrand MI, Friedman JM
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Molecular characterization of neuronal cell types based on patterns of projection with Retro-TRAP
NATURE PROTOCOLS 2015 SEP; 10(9):1319-1327
Retro-TRAP (translating ribosome affinity purification) technology enables the synthesis of molecular and neuroanatomical information through the use of transgenic and viral approaches. In contrast to other methods that are used to profile neural circuits such as laser-capture microdissection and FACS, Retro-TRAP is a high-throughput methodology that requires minimal specialized instrumentation. Retro-TRAP uses an anti-GFP ribosomal tag (expressed virally or using transgenesis) to immunoprecipitate translating mRNAs from any population of neurons that express GFP. The protocol detailed here describes the rapid extraction of molecular information from neural circuits in mice using retrograde-tracing GFP-expressing viruses. This approach can be used to identify novel cell types, as well as to molecularly profile cell types for which Cre-driver lines are available, in defined presynaptic loci. The current protocol describes a method for extracting translating mRNA from any neural circuit accessible by stereotaxic injection and manual dissection, and it takes 2-4 weeks. Although it is not described here, this mRNA can then be used in downstream processing applications such as quantitative PCR (qPCR) and high-throughput RNA sequencing to obtain 'molecular connectomic' information.
Lee JH, Leaman DP, Kim AS, de la Pena AT, Sliepen K, Yasmeen A, Derking R, Ramos A, de Taeye SW, Ozorowski G, Klein F, Burton DR, Nussenzweig MC, Poignard P, Moore JP, Klasse PJ, Sanders RW, Zwick MB, Wilson IA, Ward AB
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Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike
NATURE COMMUNICATIONS 2015 SEP; 6(?):? Article 8167
The recent identification of three broadly neutralizing antibodies (bnAbs) against gp120-gp41 interface epitopes has expanded the targetable surface on the HIV-1 envelope glycoprotein (Env) trimer. By using biochemical, biophysical and computational methods, we map the previously unknown trimer epitopes of two related antibodies, 3BC315 and 3BC176. A cryo-EM reconstruction of a soluble Env trimer bound to 3BC315 Fab at 9.3 angstrom resolution reveals that the antibody binds between two gp41 protomers, and neutralizes the virus by accelerating trimer decay. In contrast, bnAb 35O22 binding to a partially overlapping quaternary epitope at the gp120-gp41 interface does not induce decay. A conserved gp41-proximal glycan at N88 was also shown to play a role in the binding kinetics of 3BC176 and 3BC315. Finally, our data suggest that the dynamic structure of the Env trimer influences exposure of bnAb epitopes.
Ceglia I, Reitz- C, Gresack J, Ahn JH, Bustos V, Bleck M, Zhang XZ, Martin G, Simon SM, Nairn AC, Greengard P, Kim Y
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APP intracellular domain-WAVE1 pathway reduces amyloid-beta production
NATURE MEDICINE 2015 SEP; 21(9):1054-1059
An increase in amyloid-beta (A beta) production is a major pathogenic mechanism associated with Alzheimer's disease (AD)(1,2), but little is known about possible homeostatic control of the amyloidogenic pathway. Here we report that the amyloid precursor protein (APP) intracellular domain (AICD) downregulates Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous protein 1 (WAVE1 or WASF1) as part of a negative feedback mechanism to limit A beta production. The AICD binds to the Wasf1 promoter, negatively regulates its transcription and downregulates Wasf1 mRNA and protein expression in Neuro 2a (N2a) cells. WAVE1 interacts and colocalizes with APP in the Golgi apparatus. Experimentally reducing WAVE1 in N2a cells decreased the budding of APP-containing vesicles and reduced cell-surface APP, thereby reducing the production of A beta. WAVE1 downregulation was observed in mouse models of AD. Reduction of Wasf1 gene expression dramatically reduced A beta levels and restored memory deficits in a mouse model of AD. A decrease in amounts of WASF1 mRNA was also observed in human AD brains, suggesting clinical relevance of the negative feedback circuit involved in homeostatic regulation of Ab production.
Zeng WW, Pirzgalska RM, Pereira MMA, Kubasova N, Barateiro A, Seixas E, Lu YH, Kozlova A, Voss H, Martins GG, Friedman JM, Domingos AI
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Sympathetic Neuro-adipose Connections Mediate Leptin-Driven Lipolysis
CELL 2015 SEP 24; 163(1):84-94
Leptin is a hormone produced by the adipose tissue that acts in the brain, stimulating white fat breakdown. We find that the lipolytic effect of leptin is mediated through the action of sympathetic nerve fibers that innervate the adipose tissue. Using intravital two-photon microscopy, we observe that sympathetic nerve fibers establish neuro-adipose junctions, directly "enveloping'' adipocytes. Local optogenetic stimulation of sympathetic inputs induces a local lipolytic response and depletion of white adipose mass. Conversely, genetic ablation of sympathetic inputs onto fat pads blocks leptin-stimulated phosphorylation of hormone-sensitive lipase and consequent lipolysis, as do knockouts of dopamine beta-hydroxylase, an enzyme required for catecholamine synthesis. Thus, neuro-adipose junctions are necessary and sufficient for the induction of lipolysis in white adipose tissue and are an efferent effector of leptin action. Direct activation of sympathetic inputs to adipose tissues may represent an alternative approach to induce fat loss, circumventing central leptin resistance.
Conceicao T, Coelho C, Silva IS, de Lencastre H, Aires-de-Sousa M
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Staphylococcus aureus in former Portuguese colonies from Africa and the Far East: missing data to help fill the world map
CLINICAL MICROBIOLOGY AND INFECTION 2015 SEP; 21(9):? Article UNSP 842.e1
The aim of the present study was to determine the prevalence and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage among patients and healthcare workers in Angola (ANG), Sao Tome and Principe (STP), Cape Verde (CV) and East Timor (ET), and to characterize the antimicrobial susceptibility, virulence content and population structure of all S. aureus. Despite the importance of MRSA as a major human pathogen, data from these former Portuguese colonies in Africa and Asia are scarce. A total of 2065 nasal swabs recovered between 2010-14 were included in the study. Antimicrobial susceptibility testing and molecular characterization of S. aureus showed: (i) a very high MRSA prevalence in ANG (61.6%), moderate in STP (25.5%), low in CV (5.6%) and null in ET; (ii) a high prevalence of Panton-Valentine leukocidin in STP (36.8%), ET (29.2%) and CV (28.3%) contrasting with ANG (7.9%); (iii) ST5-SCCmecIVa, ST8-IV/V and ST5-VI were the major MRSA clones in ANG (65.2%), STP (44.8%) and CV (50%), respectively; (iv) a high resistance to trimethoprim-sulfamethoxazole in ANG (66.5%) and STP (50.9%), to rifampin in ANG (77.3%), and to tetracycline in STP (26.3%) and ET (20.8%); (v) three major methicillin-susceptible S. aureus clones (ST15, ST508, ST152) were present in all four countries. Age <18 years (OR 2.03, 95% CI 1.24-3.31), previous surgery (OR 2.45, 95% CI 1.24-4.83), no smoking (OR 4.04, 95% CI 1.05-15.50), and longer hospitalization (OR 2.53, 95% CI 1.49-4.28) were risk factors for MRSA carriage. This study provided the first comprehensive overview on MRSA in former Portuguese colonies in Africa and Asia, missing data in the world map. Clinical Microbiology and Infection (C) 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
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Costantini S, Crucy S, Fagot A, Garcia G, Mccartin J, Rios AAO, Poyraz D, Ryckbosch D, Diblen SS, Sigamani M, Strobbe N, Thyssen F, Tytgat M, Yazgan E, Zaganidis N, Basegmez S, Beluffi C, Bruno G, Castello R, Caudron A, Ceard L, Da Silveira GG, Delaere C, du Pree T, Favart D, Forthomme L, Giammanco A, Hollar J, Jafari A, Jez P, Komm M, Lemaitre V, Nuttens C, Pagano D, Perrini L, Pin A, Piotrzkowski K, Popov A, Quertenmont L, Selvaggi M, Marono MV, Garcia JMV, Beliy N, Caebergs T, Daubie E, Hammad GH, Alda WL, Alves GA, Brito L, Martins MC, Martins TD, Molina J, Herrera CM, Pol ME, Teles PR, Carvalho W, Chinellato J, Custodio A, Da Costa EM, Damiao DD, Martins CD, De Souza SF, Malbouisson H, Figueiredo DM, Mundim L, Nogima H, Da Silva WLP, Santaolalla J, Santoro A, Sznajder A, Manganote EJT, Pereira AV, Bernardes CA, Dogra S, Tomei TRFP, Gregores EM, Mercadante PG, Novaes SF, Padula SS, Aleksandrov A, Genchev V, Hadjiiska R, Iaydjiev P, Marinov A, Piperov S, Rodozov M, Stoykova S, Sultanov G, Vutova M, Dimitrov A, Glushkov I, Litov L, Pavlov B, Petkov P, Bian JG, Chen GM, Chen HS, Chen M, Cheng T, Du R, Jiang CH, Plestina R, Romeo F, Tao J, Wang Z, Asawatangtrakuldee C, Ban Y, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Zhang F, Zhang L, Zou W, Avila C, Cabrera A, Sierra LFC, Florez C, Gomez JP, Moreno BG, Sanabria JC, Godinovic N, Lelas D, Polic D, Puljak I, Antunovic Z, Kovac M, Brigljevic V, Kadija K, Luetic J, Mekterovic D, Sudic L, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis P, Rykaczewski H, Bodlak M, Finger M, Finger M, Assran Y, Elgammal S, Kamel AE, Radi A, Kadastik M, Murumaa M, Raidal M, Tiko A, Eerola P, Voutilainen M, Harkonen J, Karimaki V, Kinnunen R, Kortelainen MJ, Lampen T, Lassila-Perini K, Lehti S, Linden T, Luukka R, Maenpaa T, Peltola T, Tuominen E, Tuominiemi J, Tuovinen E, Wendland L, Talvitie J, Tuuva T, Besancon M, Couderc F, Dejardin M, Denegri D, Fabbro B, Faure JL, Favaro C, Ferri F, Ganjour S, Givernaud A, Gras P, de Monchenault GH, Jarry P, Locci E, Malcles J, Rander J, Rosowsky A, Titov M, Baffioni S, Beaudette F, Busson P, Chapon E, Chariot C, Dahms T, Dobrzynski L, Filipovic N, Florent A, de Cassagnac RG, Mastrolorenzo L, Mine P, Naranjo IN, Nguyen M, Ochando C, Ortona G, Paganini P, Regnard S, Salerno R, Sauvan JB, Sirois Y, Veelken C, Yilmaz Y, Zabi A, Agram JL, Andrea J, Aubin A, Bloch D, Brom JM, Chabert EC, Collard C, Conte E, Fontaine JC, Gele D, Goerlach U, Goetzmann C, Le Bihan AC, Skovpen K, Van Hove P, Gadrat S, Beauceron S, Beaupere N, Bernet C, Boudou G, Bouvier E, Brochet S, Montoya CAC, Chasserat J, Chierici R, Contardo D, Courbon B, Depasse P, El Mamouni H, Fan J, Fay J, Gascon S, Gouzevitch M, Ille B, Kurca T, Lethuillier M, Mirabito L, Pequegnot AL, Perries S, Alvarez JDR, Sabes D, Sgandurra L, Sordini V, Donckt MV, Verdier P, Viret S, Xiao H, Xiao H, Autermann C, Beranek S, Bontenackels M, Edelhoff M, Feld L, Heister A, Klein K, Lipinski M, Ostapchuk A, Preuten M, Raupach F, Sammet J, Schael S, Schulte JF, Weber H, Wittmer B, Zhukov V, Ata M, Brodski M, Dietz-Laursonn E, Duchardt D, Erdmann M, Fischer R, Guth A, Hebbeker T, Heidemann C, Hoepfner K, Klingebiel D, Knutzen S, Kreuzer R, Merschmeyer M, Meyer A, Millet P, Olschewski M, Padeken K, Papacz P, Reithler H, Schmitz SA, Sonnenschein L, Teyssier D, Thuer S, Cherepanov V, Erdogan Y, Flugge G, Geenen H, Geisler M, Ahmad WH, Hoehle F, Kargoll B, Kress T, Kuessel Y, Kunsken A, Lingemann J, Nowack A, Nugent IM, Pistone C, Pooth O, Stahl A, Martin MA, Asin I, Bartosik N, Behr J, Behrens U, Bell AJ, Bethani A, Borras K, Burgmeier A, Cakir A, Calligaris L, Campbell A, Choudhury S, Costanza F, Pardos CD, Dolinska G, Dooling S, Dorland T, Eckerlin G, Eckstein D, Eichhorn T, Flucke G, Garcia JG, Geiser A, Gizhko A, Gunnellini R, Hauk J, Hempel M, Jung H, Kalogeropoulos A, Karacheban O, Kasemann M, Katsas R, Kieseler J, Kleinwort C, Korol I, Krucker D, Lange W, Leonard J, Lipka K, Lobanov A, Lohmann W, Lutz B, Mankel R, Marfin I, Melzer-Pellmann IA, Meyer AB, Mittag G, Mnich J, Mussgiller A, Naumann-Emme S, Nayak A, Ntomari E, Perrey H, Pitzl D, Placakyte R, Raspereza A, Cipriano PMR, Roland B, Ron E, Sahin MO, Salfeld-Nebgen J, Saxena P, Schoerner-Sadenius T, Schroder M, Seitz C, Spannagel S, Trevino ADRV, Walsh R, Wissing C, Blobel V, Vignali MC, Draeger AR, Erfle J, Garutti E, Goebel K, Gorner M, Haller J, Hoffmann M, Hoing RS, Junkes A, Kirschenmann H, Klanner R, Kogler R, Lapsien T, Lenz T, Marchesini I, Marconi D, Ott J, Peiffer T, Perieanu A, Pietsch N, Poehlsen J, Poehlsen T, Rathjens D, Sander C, Schettler H, Schleper P, Schlieckau E, Schmidt A, Seidel M, Sola V, Stadie H, Steinbruck G, Troendle D, Usai E, Vanelderen L, Vanhoefer A, Barth C, Baus C, Berger J, Boser C, Butz E, Chwalek T, De Boer W, Descroix A, Dierlamm A, Feindt M, Frensch F, Giffels M, Gilbert A, Hartmann F, Hauth T, Husemann U, Katkov I, Kornmayer A, Pardo RL, Mozer MU, Muller T, Muller T, Nurnberg A, Quast G, Rabbertz K, Rocker S, Simonis HJ, Stober FM, Ulrich R, Wagner-Kuhr J, Wayand S, Weiler T, Wolf R, Anagnostou G, Daskalakis G, Geralis T, Giakoumopoulou VA, Kyriakis A, Loukas D, Markou A, Markou C, Psallidas A, Topsis-Giotis I, Agapitos A, Kesisoglou S, Panagiotou A, Saoulidou N, Stiliaris E, Tziaferi E, Aslanoglou X, Evangelou I, Flouris G, Foudas C, Kokkas P, Manthos N, Papadopoulos I, Paradas E, Strologas J, Bencze G, Hajdu C, Hidas P, Horvath D, Sikler F, Veszpremi V, Vesztergombi G, Zsigmond AJ, Beni N, Czellar S, Karancsi J, Molnar J, Palinkas J, Szillasi Z, Makovec A, Raics P, Trocsanyi ZL, Ujvari B, Swain SK, Beri SB, Bhatnagar V, Gupta R, Bhawandeep U, Kalsi AK, Kaur M, Kumar R, Mittal M, Nishu N, Singh JB, Kumar A, Kumar A, Ahuja S, Bhardwaj A, Choudhary BC, Kumar A, Malhotra S, Naimuddin M, Ranjan K, Sharma V, Banerjee S, Bhattacharya S, Chatterjee K, Dutta S, Gomber B, Jain S, Jain S, Khurana R, Modak A, Mukherjee S, Roy D, Sarkar S, Sharan M, Abdulsalam A, Dutta D, Kumar 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Rovelli T, Siroli GP, Tosi N, Travaglini R, Albergo S, Cappello G, Chiorboli M, Costa S, Giordano F, Potenza R, Tricomi A, Tuve C, Barbagli G, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Gallo E, Gonzi S, Gori V, Lenzi P, Meschini M, Paoletti S, Sguazzoni G, Tropiano A, Benussi L, Bianco S, Fabbri F, Piccolo D, Ferretti R, Ferro F, Lo Vetere M, Robutti E, Tosi S, Dinardo ME, Fiorendi S, Gennai S, Gerosa R, Ghezzi A, Govoni P, Lucchini MT, Malvezzi S, Manzoni RA, Martelli A, Marzocchi B, Menasce D, Moroni L, Paganoni M, Pedrini D, Ragazzi S, Redaelli N, de Fatis TT, Buontempo S, Cavallo N, Di Guida S, Fabozzi F, Iorio AOM, Lista L, Meola S, Merola M, Paolucci P, Azzi P, Bacchetta N, Bellato M, Bisello D, Carlin R, De Oliveira ACA, Checchia R, Dall'Osso M, Dorigo T, Dosselli U, Fanzago F, Gasparini F, Gasparini U, Gozzelino A, Lacaprara S, Margoni M, Meneguzzo AT, Pazzini J, Pozzobon N, Ronchese P, Simonetto F, Torassa E, Tosi M, Zotto P, Zucchetta A, Zumerle G, Gabusi M, Ratti SP, 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R, Solano A, Staiano A, Tamponi U, Belforte S, Candelise V, Casarsa M, Cossutti F, Della Ricca G, Gobbo B, La Licata C, Marone M, Schizzi A, Umer T, Zanetti A, Chang S, Kropivnitskaya A, Nam SK, Kim DH, Kim GN, Kim MS, Kong DJ, Lee S, Oh YD, Park H, Sakharov A, Son DC, Kim TJ, Ryu MS, Kim JY, Moon DH, Song S, Choi S, Gyun D, Hong B, Jo M, Kim H, Kim Y, Lee B, Lee KS, Park SK, Roh Y, Yoo HD, Choi M, Kim JH, Park IC, Ryu G, Choi Y, Choi YK, Goh J, Kim D, Kwon E, Lee J, Yu I, Juodagalvis A, Komaragiri JR, Ali MABM, Abdullah WATW, Linares EC, Castilla-Valdez H, De La Cruz-Burelo E, Heredia-de La Cruz I, Hernandez-Almada A, Lopez-Fernandez R, Sanchez-Hernandez A, Moreno SC, Valencia FV, Pedraza I, Ibarguen HAS, Pineda AM, Krofcheck D, Butler PH, Reucroft S, Ahmad A, Ahmad M, Hassan Q, Hoorani HR, Khan WA, Khurshid T, Shoaib M, Bialkowska H, Bluj M, Boimska B, Frueboes T, Gorski M, Kazana M, Nawrocki K, Romanowska-Rybinska K, Szleper M, Zalewski P, Brona G, Bunkowski K, Cwiok M, Dominik W, 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Petrushanko S, Savrin V, Snigirev A, Azhgirey I, Bayshev I, Bitioukov S, Kachanov V, Kalinin A, Konstantinov D, Krychkine V, Petrov V, Ryutin R, Sobol A, Tourtchanovitch L, Troshin S, Tyurin N, Uzunian A, Volkov A, Adzic P, Ekmedzic M, Milosevic J, Rekovic V, Maestre JA, Battilana C, Calvo E, Cerrada M, Llatas MC, Colino N, De la Cruz B, Peris AD, Vazquez DD, Del Valle AE, Bedoya CF, Ramos JPF, Flix J, Fouz MC, Garcia-Abia P, Lopez OG, Lopez SG, Hernandez JM, Josa MI, De Martino EN, Yzquierdo APC, Pelayo JP, Olmeda AQ, Redondo I, Romero L, Soares MS, Albajar C, de Troconiz JF, Missiroli M, Moran D, Brun H, Cuevas J, Menendez JF, Folgueras S, Caballero IG, Cifuentes JAB, Cabrillo IJ, Calderon A, Campderros JD, Fernandez M, Gomez G, Graziano A, Virto AL, Marco J, Marco R, Rivero CM, Matorras F, Sanchez FJM, Gomez JP, Rodrigo T, Rodriguez-Marrero AY, Ruiz-Jimeno A, Scodellaro L, Vila I, Cortabitarte RV, Abbaneo D, Auffray E, Auzinger G, Bachtis M, Baillon P, Ball AH, Barney D, Benaglia A, Bendavid J, Benhabib L, Benitez JF, Bloch P, Bocci A, Bonato A, Bondu O, Botta C, Breuker H, Camporesi T, Cerminara G, Colafranceschi S, D'Alfonso M, d'Enterria D, Dabrowski A, David A, De Guio F, De Roeck A, De Visscher S, Di Marco E, Dobson M, Dordevic M, Dorney B, Dupont-Sagorin N, Elliott-Peisert A, Franzoni G, Funk W, Gigi D, Gill K, Giordano D, Girone M, Glege F, Guida R, Gundacker S, Guthoff M, Hammer J, Hansen M, Harris P, Hegeman J, Innocente V, Janot P, Kousouris K, Krajczar K, Lecoq P, Lourenco C, Magini N, Malgeri L, Mannelli M, Marrouche J, Masetti L, Meijers F, Mersi S, Meschi E, Moortgat F, Morovic S, Mulders M, Orfanelli S, Orsini L, Pape L, Perez E, Petrilli A, Petrucciani G, Pfeiffer A, Pimia M, Piparo D, Plagge M, Racz A, Rolandi G, Rovere M, Sakulin H, Schafer C, Schwick C, Sharma A, Siegrist P, Silva P, Simon M, Sphicas P, Spiga D, Steggemann J, Stieger B, Stoye M, Takahashi Y, Treille D, Tsirou A, Veres GI, Wardle N, Wohri HK, Wollny H, Zeuner WD, Bertl W, Deiters K, Erdmann W, Horisberger R, Ingram Q, Kaestli HC, Kotlinski D, Langenegger U, Renker D, Rohe T, Bachmair F, Bani L, Bianchini L, Buchmann MA, Casal B, Chanon N, Dissertori G, Dittmar M, Donega M, Duenser M, Eller R, Grab C, Hits D, Hoss J, Kasieczka G, Lustermann W, Mangano B, Marini AC, Marionneau M, del Arbol PMR, Masciovecchio M, Meister D, Mohr N, Musella P, Nageli C, Nessi-Tedaldi F, Pandolfi F, Pauss F, Perrozzi L, Peruzzi M, Quittnat M, Rebane L, Rossini M, Starodumov A, Takahashi M, Theofilatos K, Wallny R, Weber HA, Amsler C, Canelli MF, Chiochia V, De Cosa A, Galloni C, Hinzmann A, Hreus T, Kilminster B, Lange C, Ngadiuba J, Pinna D, Robmann P, Ronga FJ, Taroni S, Yang Y, Cardaci M, Chen KH, Ferro C, Kuo CM, Lin W, Lu YJ, Volpe R, Yu SS, Chang P, Chang YH, Chao Y, Chen KF, Chen PH, Dietz C, Grundler U, Hou WS, Liu YF, Lu RS, Moya MM, Petrakou E, Tsai JF, Tzeng YM, Wilken R, Asavapibhop B, Singh G, Srimanobhas N, Suwonjandee N, Adiguzel A, Bakirci MN, Cerci S, Dozen C, Dumanoglu I, Eskut E, Girgis S, Gokbulut G, Guler Y, Gurpinar E, Hos I, Kangal EE, Topaksu AK, Onengut G, Ozdemir K, Ozturk S, Polatoz A, Cerci DS, Tali B, Topakli H, Vergili M, Zorbilmez C, Akin IV, Bilin B, Bilmis S, Gamsizkan H, Isildak B, Karapinar G, Ocalan K, Sekmen S, Surat UE, Yalvac M, Zeyrek M, Albayrak EA, Gulmez E, Kaya M, Kaya O, Yetkin T, Cankocak K, Vardarh FI, Levchuk L, Sorokin P, Brooke JJ, Clement E, Cussans D, Flacher H, Goldstein J, Grimes M, Heath GP, Heath HF, Jacob J, Kreczko L, Lucas C, Meng Z, Newbold DM, Paramesvaran S, Poll A, Sakuma T, El Nasr-Storey SS, Senkin S, Smith VJ, Bell KW, Belyaev A, Brew C, Brown RM, Cockerill DJA, Coughlan JA, Harder K, Harper S, Olaiya E, Petyt D, Shepherd-Themistocleous CH, Thea A, Tomalin IR, Williams T, Womersley WJ, Worm SD, Baber M, Bainbridge R, Buchmuller O, Burton D, Colling D, Cripps N, Dauncey P, Davies G, Della Negra M, Dunne P, Elwood A, Ferguson W, Fulcher J, Futyan D, Hall G, Iles G, Jarvis M, Karapostoli G, Kenzie M, Lane R, Lucas R, Lyons L, Magnan AM, Malik S, Mathias B, Nash J, Nikitenko A, Pela J, Pesaresi M, Petridis K, Raymond DM, Rogerson S, Rose A, Seez C, Sharp P, Tapper A, Acosta MV, Virdee T, Zenz SC, Cole JE, Hobson PR, Khan A, Kyberd P, Leggat D, Leslie D, Reid ID, Symonds P, Teodorescu L, Turner M, Dittmann J, Hatakeyama K, Kasmi A, Liu H, Pastika N, Scarborough T, Wu Z, Charaf O, Cooper SI, Henderson C, Rumerio P, Avetisyan A, Bose T, Fantasia C, Lawson P, Richardson C, Rohlf J, John JS, Sulak L, Alimena J, Berry E, Bhattacharya S, Christopher G, Cutts D, Demiragli Z, Dhingra N, Ferapontov A, Garabedian A, Heintz U, Laird E, Landsberg G, Mao Z, Narain M, Sagir S, Sinthuprasith T, Speer T, Swanson J, Breedon R, Breto G, Sanchez MCD, Chauhan S, Chertok M, Conway J, Conway R, Cox PT, Erbacher R, Gardner M, Ko W, Lander R, Mulhearn M, Pellett D, Pilot J, Ricci-Tam F, Shalhout S, Smith J, Squires M, Stolp D, Tripathi M, Wilbur S, Yohay R, Cousins R, Everaerts P, Farrell C, Hauser J, Ignatenko M, Rakness G, Takasugi E, Valuev V, Weber M, Burt K, Clare R, Ellison J, Gary JW, Hanson G, Heilman J, Rikova MI, Jandir P, Kennedy E, Lacroix F, Long OR, Luthra A, Malberti M, Negrete MO, Shrinivas A, Sumowidagdo S, Wimpenny S, Branson JG, Cerati GB, Cittolin S, D'Agnolo RT, Holzner A, Kelley R, Klein D, Letts J, Macneill I, Olivito D, Padhi S, Palmer C, Pieri M, Sani M, Sharma V, Simon S, Tadel M, Tu Y, Vartak A, Welke C, Wurthwein F, Yagil A, Della Porta GZ, Barge D, Bradmiller-Feld J, Campagnari C, Danielson T, Dishaw A, Dutta V, Flowers K, Sevilla MF, Geffert P, George C, Golf F, Gouskos L, Incandela J, Justus C, Mccoll N, Mullin SD, Richman J, Stuart D, To W, West C, Yoo J, Apresyan A, Bornheim A, Bunn J, Chen Y, Duarte J, Mott A, Newman HB, Pena C, Pierini M, Spiropulu M, Vlimant JR, Wilkinson R, Xie S, Zhu RY, Azzolini V, Calamba A, Carlson B, Ferguson T, Iiyama Y, Paulini M, Russ J, Vogel H, Vorobiev I, Cumalat JP, Ford WT, Gaz A, Krohn M, Lopez EL, Nauenberg U, Smith JG, Stenson K, Wagner SR, Alexander J, Chatterjee A, Chaves J, Chu J, Dittmer S, Eggert N, Mirman N, Kaufman GN, Patterson JR, Ryd A, Salvati E, Skinnari L, Sun W, Teo WD, Thom J, Thompson J, Tucker J, Weng Y, Winstrom L, Wittich P, Winn D, Abdullin S, Albrow M, Anderson J, Apollinari G, Bauerdick LAT, Beretvas A, Berryhill J, Bhat PC, Bolla G, Burkett K, Butler JN, Cheung HWK, Chlebana F, Cihangir S, Elvira VD, Fisk I, Freeman J, Gottschalk E, Gray L, Green D, Gruenendahl S, Gutsche O, Hanlon J, Hare D, Harris RM, Hirschauer J, Hooberman B, Jindariani S, Johnson M, Joshi U, Klima B, Kreis B, Kwan S, Linacre J, Lincoln D, Lipton R, Liu T, De Sa RL, Lykken J, Maeshima K, Marraffino JM, Outschoorn VIM, Maruyama S, Mason D, McBride P, Merkel P, Mishra K, Mrenna S, Nahn S, Newman-Holmes C, O'Dell V, Prokofyev O, Sexton-Kennedy E, Soha A, Spalding WJ, Spiegel L, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vidal R, Whitbeck A, Whitmore J, Yang F, Acosta D, Avery P, Bortignon P, Bourilkov D, Carver M, Curry D, Das S, De Gruttola M, Di Giovanni GP, Field RD, Fisher M, Furic IK, Hugon J, Konigsberg J, Korytov A, Kypreos T, Low JF, Matchev K, Mei H, Milenovic P, Mitselmakher G, Muniz L, Rinkevicius A, Shchutska L, Snowball M, Sperka D, Yelton J, Zakaria M, Hewamanage S, Linn S, Markowitz P, Martinez G, Rodriguez JL, Adams JR, Adams T, Askew A, Bochenek J, Diamond B, Haas J, Hagopian S, Hagopian V, Johnson KF, Prosper H, Veeraraghavan V, Weinberg M, Baarmand MM, Hohlmann M, Kalakhety H, Yumiceva F, Adams MR, Apanasevich L, Berry D, Betts RR, Bucinskaite I, Cavanaugh R, Evdokimov O, Gauthier L, Gerber CE, Hofman DJ, Kurt P, O'Brien C, Gonzalez IDS, Silkworth C, Turner P, Varelas N, Bilki B, Clarida W, Dilsiz K, Haytmyradov M, Khristenko V, Merlo JR, Mermerkaya H, Mestvirishvili A, Moeller A, Nachtman J, Ogul H, Onel Y, Ozok F, Penzo A, Rahmat R, Sen S, Tan P, Tiras E, Wetzel J, Yi K, Anderson I, Barnett BA, Blumenfeld B, Bolognesi S, Fehling D, Gritsan AV, Maksimovic P, Martin C, Swartz M, Xiao M, Baringer P, Bean A, Benelli G, Bruner C, Gray J, Kenny RP, Majumder D, Malek M, Murray M, Noonan D, Sanders S, Sekaric J, Stringer R, Wang Q, Wood JS, Chakaberia I, Ivanov A, Kaadze K, Khalil S, Makouski M, Maravin Y, Saini LK, Skhirtladze N, Svintradze I, Gronberg J, Lange D, Rebassoo F, Wright D, Baden A, Belloni A, Calvert B, Eno SC, Gomez JA, Hadley NJ, Jabeen S, Kellogg RG, Kolberg T, Lu Y, Mignerey AC, Pedro K, Skuja A, Tonjes MB, Tonwar SC, Apyan A, Barbieri R, Bierwagen K, Busza W, Cali IA, Di Matteo L, Ceballos GG, Goncharov M, Gulhan D, Klute M, Lai YS, Lee YJ, Levin A, Luckey PD, Paus C, Ralph D, Roland C, Roland G, Stephans GSF, Sumorok K, Velicanu D, Veverka J, Wyslouch B, Yang M, Zanetti M, Zhukova V, Dahmes B, Gude A, Kao SC, Klapoetke K, Kubota Y, Mans J, Nourbakhsh S, Rusack R, Singovsky A, Tambe N, Turkewitz J, Acosta JG, Oliveros S, Avdeeva E, Bloom K, Bose S, Claes DR, Dominguez A, Suarez RG, Keller J, Knowlton D, Kravchenko I, Lazo-Flores J, Meier F, Ratnikov F, Snow GR, Zvada M, Dolen J, Godshalk A, Iashvili I, Kharchilava A, Kumar A, Rappoccio S, Alverson G, Barberis E, Baumgartel D, Chasco M, Massironi A, Morse DM, Nash D, Orimoto T, Trocino D, Wang RJ, Wood D, Zhang J, Hahn KA, Kubik A, Mucia N, Odell N, Pollack B, Pozdnyakov A, Schmitt M, Stoynev S, Sung K, Velasco M, Won S, Brinkerhoff A, Chan KM, Drozdetskiy A, Hildreth M, Jessop C, Karmgard DJ, Kellams N, Lannon K, Lynch S, Marinelli N, Musienko Y, Pearson T, Planer M, Ruchti R, Smith G, Valls N, Wayne M, Wolf M, Woodard A, Antonelli L, Brinson J, Bylsma B, Durkin LS, Flowers S, Hart A, Hill C, Hughes R, Kotov K, Ling TY, Luo W, Puigh D, Rodenburg M, Winer BL, Wolfe H, Wulsin HW, Driga O, Elmer P, Hardenbrook J, Hebda P, Koay SA, Lujan P, Marlow D, Medvedeva T, Mooney M, Olsen J, Piroue P, Quan X, Saka H, Stickland D, Tully C, Werner JS, Zuranski A, Brownson E, Malik S, Mendez H, Vargas JER, Barnes VE, Benedetti D, Bortoletto D, Gutay L, Hu Z, Jha MK, Jones M, Jung K, Kress M, Leonardo N, Miller DH, Neumeister N, Primavera F, Radburn-Smith BC, Shi X, Shipsey I, Silvers D, Svyatkovskiy A, Wang F, Xie W, Xu L, Zablocki J, Parashar N, Stupak J, Adair A, Akgun B, Ecklund KM, Geurts FJM, Li W, Michlin B, Padley BP, Redjimi R, Roberts J, Zabel J, Betchart B, Bodek A, De Barbaro P, Demina R, Eshaq Y, Ferbel T, Galanti M, Garcia-Bellido A, Goldenzweig P, Han J, Harel A, Hindrichs O, Khukhunaishvili A, Korjenevski S, Petrillo G, Verzetti M, Vishnevskiy D, Ciesielski R, Demortier L, Goulianos K, Mesropian C, Arora S, Barker A, Chou JP, Contreras-Campana C, Contreras-Campana E, Duggan D, Ferencek D, Gershtein Y, Gray R, Halkiadakis E, Hidas D, Kaplan S, Lath A, Panwalkar S, Park M, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Rose K, Spanier S, York A, Bouhali O, Hernandez AC, Dalchenko M, De Mattia M, Dildick S, Eusebi R, Flanagan W, Gilmore J, Kamon T, Khotilovich V, Krutelyov V, Montalvo R, Osipenkov I, Pakhotin Y, Patel R, Perloff A, Roe J, Rose A, Safonov A, Suarez I, Tatarinov A, Ulmer KA, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero R, Faulkner J, Kovitanggoon K, Kunori S, Lee SW, Libeiro T, Volobouev I, Appelt E, Delannoy AG, Greene S, Gurrola A, Johns W, Maguire C, Mao Y, Melo A, Sharma M, Sheldon P, Snook B, Tuo S, Velkovska J, Arenton MW, Boutle S, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Lin C, Neu C, Wolfe E, Wood J, Clarke C, Harr R, Karchin PE, Don CKK, Lamichhane P, Sturdy J, Belknap DA, Carlsmith D, Cepeda M, Dasu S, Dodd L, Duric S, Friis E, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Lanaro A, Lazaridis C, Levine A, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ross I, Sarangi T, Savin A, Smith WH, Taylor D, Vuosalo C, Woods N
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Search for narrow high-mass resonances in proton-proton collisions at root s=8 TeV decaying to a Z and a Higgs boson
PHYSICS LETTERS B 2015 SEP 2; 748(?):255-277
A search for a narrow, high-mass resonance decaying into Z and Higgs ( H) bosons is presented. The final state studied consists of a merged jet pair and a tau pair resulting from the decays of Z and H bosons, respectively. The analysis is based on a data sample of proton-proton collisions at a center-of mass energy of 8 TeV, collected with the CMS experiment in 2012, and corresponding to an integrated luminosity of 19.7 fb(-1). In the resonance mass range of interest, which extends from 0.8 to 2.5 TeV, the Z and H bosons are produced with large momenta, which implies that the final products of the two quarks or the two tau leptons must be detected within a small angular interval. From a combination of all possible decay modes of the tau leptons, production cross sections in a range between 0.9 and 27.8 fb are excluded at 95% confidence level, depending on the resonance mass. (C) 2015 CERN for the benefit of the CMS Collaboration. Published by Elsevier B.V.
Fiscella K, Tobin JN, Carroll JK, He H, Ogedegbe G
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Ethical oversight in quality improvement and quality improvement research: new approaches to promote a learning health care system
BMC MEDICAL ETHICS 2015 SEP 17; 16(?):? Article 63
Background: Institutional review boards (IRBs) distinguish health care quality improvement (QI) and health care quality improvement research (QIR) based primarily on the rigor of the methods used and the purported generalizability of the knowledge gained. Neither of these criteria holds up upon scrutiny. Rather, this apparently false dichotomy may foster under-protection of participants in QI projects and over-protection of participants within QIR. Discussion: Minimal risk projects should entail minimal oversight including waivers for informed consent for both QI and QIR projects. Minimizing the burdens of conducting QIR, while ensuring minimal safeguards for QI projects, is needed to restore this imbalance in oversight. Potentially, such ethical oversight could be provided by the integration of Institutional Review Boards and Clinical Ethical Committees, using a more integrated and streamlined approach such as a two-step process involving a screening review, followed by a review by committee trained in QIR. Standards for such ethical review and training in these standards, coupled with rapid review cycles, could facilitate an appropriate level of oversight within the context of creating and sustaining learning health care systems. Summary: We argue that QI and QIR are not reliably distinguishable. We advocate for approaches that improve protections for QI participants while minimizing over-protection for participants in QIR through reasonable ethical oversight that aligns risk to participants in both QI and QIR with the needs of a learning health care system.
Goodman G, Poznanski RR, Cacha L, Bercovich D
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The Two-Brains Hypothesis: Towards a guide for brain-brain and brain-machine interfaces
JOURNAL OF INTEGRATIVE NEUROSCIENCE 2015 SEP; 14(3):281-293
Great advances have been made in signaling information on brain activity in individuals, or passing between an individual and a computer or robot. These include recording of natural activity using implants under the scalp or by external means or the reverse feeding of such data into the brain. In one recent example, noninvasive transcranial magnetic stimulation (TMS) allowed feeding of digitalized information into the central nervous system (CNS). Thus, noninvasive electroencephalography (EEG) recordings of motor signals at the scalp, representing specific motor intention of hand moving in individual humans, were fed as repetitive transcranial magnetic stimulation (rTMS) at a maximum intensity of 2.0T through a circular magnetic coil placed flush on each of the heads of subjects present at a different location. The TMS was said to induce an electric current influencing axons of the motor cortex causing the intended hand movement: the first example of the transfer of motor intention and its expression, between the brains of two remote humans. However, to date the mechanisms involved, not least that relating to the participation of magnetic induction, remain unclear. In general, in animal biology, magnetic fields are usually the poor relation of neuronal current: generally "unseen" and if apparent, disregarded or just given a nod. Niels Bohr searched for a biological parallel to complementary phenomena of physics. Pertinently, the two-brains hypothesis (TBH) proposed recently that advanced animals, especially man, have two brains i.e., the animal CNS evolved as two fundamentally different though interdependent, complementary organs: one electro-ionic (tangible, known and accessible), and the other, electromagnetic (intangible and difficult to access) - a stable, structured and functional 3D compendium of variously induced interacting electro-magnetic (EM) fields. Research on the CNS in health and disease progresses including that on brain-brain, brain-computer and brain-robot engineering. As they grow even closer, these disciplines involve their own unique complexities, including direction by the laws of inductive physics. So the novel TBH hypothesis has wide fundamental implications, including those related to TMS. These require rethinking and renewed research engaging the fully complementary equivalence of mutual magnetic and electric field induction in the CNS and, within this context, a new mathematics of the brain to decipher higher cognitive operations not possible with current brain-brain and brain-machine interfaces. Bohr may now rest.
Wu YG, Barad DH, Kushnir VA, Lazzaroni E, Wang Q, Albertini DF, Gleicher N
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Aging-related premature luteinization of granulosa cells is avoided by early oocyte retrieval
JOURNAL OF ENDOCRINOLOGY 2015 SEP; 226(3):167-180
Why IVF pregnancy rates decline sharply after age 43 is unknown. In this study, we compared granulosa cell (GC) function in young oocyte donors (n=31, ages 21-29), middle-aged (n=64, ages 30-37) and older infertile patients (n=41, ages 43-47). Gene expressions related to gonadotropin activity, steroidogenesis, apoptosis and luteinization were examined by real-time PCR and western blot in GCs collected from follicular fluid. FSH receptor (FSHR), aromatase (CYP19A1) and 17 beta-hydroxysteroid dehydrogenase (HSD17B) expression were found down regulated with advancing age, while LH receptor (LHCGR), P450scc (CYP11A1) and progesterone receptor (PGR) were up regulated. Upon in vitro culture, GCs were found to exhibit lower proliferation and increased apoptosis with aging. While FSH supplementation stimulated GCs growth and prevented luteinization in vitro. These observations demonstrate age-related functional declines in GCs, consistent with premature luteinization. To avoid premature luteinization in women above age 43, we advanced oocyte retrieval by administering human chorionic gonadotropin at maximal leading follicle size of 16 mm (routine 19-21 mm). Compared to normal cycles in women of similar age, earlier retrieved patients demonstrated only a marginal increase in oocyte prematurity, yet exhibited improved embryo numbers as well as quality and respectable clinical pregnancy rates. Premature follicular luteinization appears to contribute to rapidly declining IVF pregnancy chances after age 43, and can be avoided by earlier oocyte retrieval.
Gerber A, Saini C, Curie T, Emmenegger Y, Rando G, Gosselin P, Gotic I, Gos P, Franken P, Schibler U
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The systemic control of circadian gene expression
DIABETES OBESITY & METABOLISM 2015 SEP; 17(?):23-32
The mammalian circadian timing system consists of a central pacemaker in the brain's suprachiasmatic nucleus (SCN) and subsidiary oscillators in nearly all body cells. The SCN clock, which is adjusted to geophysical time by the photoperiod, synchronizes peripheral clocks through a wide variety of systemic cues. The latter include signals depending on feeding cycles, glucocorticoid hormones, rhythmic blood-borne signals eliciting daily changes in actin dynamics and serum response factor (SRF) activity, and sensors of body temperature rhythms, such as heat shock transcription factors and the cold-inducible RNA-binding protein CIRP. To study these systemic signalling pathways, we designed and engineered a novel, highly photosensitive apparatus, dubbed RT-Biolumicorder. This device enables us to record circadian luciferase reporter gene expression in the liver and other organs of freely moving mice over months in real time. Owing to the multitude of systemic signalling pathway involved in the phase resetting of peripheral clocks the disruption of any particular one has only minor effects on the steady state phase of circadian gene expression in organs such as the liver. Nonetheless, the implication of specific pathways in the synchronization of clock gene expression can readily be assessed by monitoring the phase-shifting kinetics using the RT-Biolumicorder.