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Found 37684 matches. Displaying 6221-6230
Alsina L, Israelsson E, Altman MC, Dang KK, Ghandil P, Israel L, von Bernuth H, Baldwin N, Qin H, Jin Z, Banchereau R, Anguiano E, Ionan A, Abel L, Puel A, Picard C, Pascual V, Casanova JL, Chaussabel D
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A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4
NATURE IMMUNOLOGY 2014 DEC; 15(12):1134-1142
Loss of function of the kinase IRAK4 or the adaptor MyD88 in humans interrupts a pathway critical for pathogen sensing and ignition of inflammation. However, patients with loss-of-function mutations in the genes encoding these factors are, unexpectedly, susceptible to only a limited range of pathogens. We employed a systems approach to investigate transcriptome responses following in vitro exposure of patients' blood to agonists of Toll-like receptors (TLRs) and receptors for interleukin 1 (IL-1Rs) and to whole pathogens. Responses to purified agonists were globally abolished, but variable residual responses were present following exposure to whole pathogens. Further delineation of the latter responses identified a narrow repertoire of transcriptional programs affected by loss of MyD88 function or IRAK4 function. Our work introduces the use of a systems approach for the global assessment of innate immune responses and the characterization of human primary immunodeficiencies.
Carvalho AS, Ribeiro H, Voabil P, Penque D, Jensen ON, Molina H, Matthiesen R
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Global Mass Spectrometry and Transcriptomics Array Based Drug Profiling Provides Novel Insight into Glucosamine Induced Endoplasmic Reticulum Stress
MOLECULAR & CELLULAR PROTEOMICS 2014 DEC; 13(12):3294-3307
We investigated the molecular effects of glucosamine supplements, a popular and safe alternative to nonsteroidal anti-inflammatory drugs, for decreasing pain, inflammation, and maintaining healthy joints. Numerous studies have reported an array of molecular effects after glucosamine treatment. We questioned whether the differences in the effects observed in previous studies were associated with the focus on a specific subproteome or with the use of specific cell lines or tissues. To address this question, global mass spectrometry- and transcription array-based glucosamine drug profiling was performed on malignant cell lines from different stages of lymphocyte development. We combined global label-free MS-based protein quantitation with an open search for modifications to obtain the best possible proteome coverage. Our data were largely consistent with previous studies in a variety of cellular models. We mainly observed glucosamine induced O-GlcNAcylation/O-GalNAcylation (O-HexNAcylation); however, we also observed global and local changes in acetylation, methylation, and phosphorylation. For example, our data provides two additional examples of "yinyang" between phosphorylation and O-HexNAcylation. Furthermore, we mapped novel O-HexNAc sites on GLU2B and calnexin. GLU2B and calnexin are known to be located in the endoplasmic reticulum (ER) and involved in protein folding and quality control. The O-HexNAc sites were regulated by glucosamine treatment and correlated with the up-regulation of the ER stress marker GRP78. The occupancy of O-HexNAc on GLU2B and calnexin sites differed between the cytosolic and nuclear fractions with a higher occupancy in the cytosolic fraction. Based on our data we propose the hypothesis that O-HexNAc either inactivates calnexin and/or targets it to the cytosolic fraction. Further, we hypothesize that O-HexNAcylation induced by glucosamine treatment enhances protein trafficking.
Maglione PJ, Simchoni N, Black S, Radigan L, Overbey JR, Bagiella E, Bussel JB, Bossuyt X, Casanova JL, Meyts I, Cerutti A, Picard C, Cunningham-Rundles C
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IRAK-4 and MyD88 deficiencies impair IgM responses against T-independent bacterial antigens
BLOOD 2014 DEC 4; 124(24):3561-3571
IRAK-4 and MyD88 deficiencies impair interleukin 1 receptor and Toll-like receptor (TLR) signaling and lead to heightened susceptibility to invasive bacterial infections. Individuals with these primary immunodeficiencies have fewer immunoglobulin M (IgM)(+)IgD(+)CD27(+) B cells, a population that resembles murine splenic marginal zone B cells that mount T-independent antibody responses against bacterial antigens. However, the significance of this B-cell subset in humans is poorly understood. Using both a 610 carbohydrate array and enzyme-linked immunosorbent assay, we found that patients with IRAK-4 and MyD88 deficiencies have reduced serum IgM, but not IgG antibody, recognizing T-independent bacterial antigens. Moreover, the quantity of specific IgM correlated with IgM(+)IgD(+)CD27(+) B-cell frequencies. As with mouse marginal zone B cells, human IgM(+)CD27(+) B cells activated by TLR7 or TLR9 agonists produced phosphorylcholine-specific IgM. Further linking splenic IgM(+)IgD(+)CD27(+) B cells with production of T-independent IgM, serum from splenectomized subjects, who also have few IgM(+)IgD(+)CD27(+) B cells, had reduced antibacterial IgM. IRAK-4 and MyD88 deficiencies impaired TLR-induced proliferation of this B-cell subset, suggesting a means by which loss of this activation pathway leads to reduced cell numbers. Thus, by bolstering the IgM(+)IgD(+)CD27(+) B-cell subset, IRAK-4 and MyD88 promote optimal T-independent IgM antibody responses against bacteria in humans.
Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, Ero J, Fabjan C, Friedl M, Fruhwirth R, Ghete VM, Hartl C, Hormann N, Hrubec J, Jeitler M, Kiesenhofer W, Knunz V, Krammer M, Kratschmer I, Liko D, Mikulec I, Rabady D, Rahbaran B, Rohringer H, Schofbeck R, Strauss J, Taurok A, Treberer-Treberspurg W, Waltenberger W, Wulz CE, Mossolov V, Shumeiko N, Gonzalez JS, Alderweireldt S, Bansal M, Bansal S, Cornelis T, De Wolf EA, Janssen X, Knutsson A, Luyckx S, Ochesanu S, Roland B, Rougny R, Van de Klundert M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Van Spilbeeck A, Blekman F, Blyweert S, D'Hondt J, Daci N, Heracleous N, Keaveney J, Lowette S, Maes M, Olbrechts A, Python Q, Strom D, Tavernier S, Van Doninck W, Van Mulders P, Van Onsem GP, Villella I, Caillol C, Clerbaux B, De Lentdecker G, Dobur D, Favart L, Gay APR, Grebenyuk A, Leonard A, Mohammadi A, Pernie L, Reis T, Seva T, Thomas L, Vander Velde C, Vanlaer P, Wang J, Adler V, Beernaert K, Benucci L, Cimmino A, Costantini S, Crucy S, Dildick S, Fagot A, Garcia G, Mccartin J, Rios AAO, 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, 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, Herrera CM, Pol ME, 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, Iaydjiev P, Marinov A, Piperov S, Rodozov M, Stoykova S, Sultanov G, Tcholakov V, Vutova M, Dimitrov A, Glushkov I, Hadjiiska R, Kozhuharov V, Litov L, Pavlov B, Petkov P, Bian JG, Chen GM, Chen HS, Chen M, Du R, Jiang CH, Liang S, Plestina R, Tao J, Wang X, Wang Z, Asawatangtrakuldee C, Ban Y, Guo Y, Li Q, Li W, Liu S, Mao Y, Qian SJ, Wang D, Zhang L, Zou W, Avila C, 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 PA, Bodlak M, Finger M, Finger M, Assran Y, Kamel AE, Mahmoud MA, Radi A, Kadastik M, Murumaa M, Raidal M, Tiko A, Eerola P, Fedi G, Voutilainen M, Harkonen J, Karimaki V, Kinnunen R, Kortelainen MJ, Lampen T, Lassila-Perini K, Lehti S, Linden T, Luukka P, Maenpaa T, Peltola T, Tuominen E, Tuominiemi J, Tuovinen E, Wendland L, 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, Charlot C, Dahms T, Dalchenko M, Dobrzynski L, Filipovic N, Florent A, de Cassagnac RG, Mastrolorenzo L, Mine P, Mironov C, Naranjo IN, Nguyen M, Ochando C, 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, Van Hove P, Gadrat S, Beauceron S, Beaupere N, Boudoul G, Bouvier E, Brochet S, Montoya CAC, Chasserat J, Chierici R, Contardo D, Depasse P, El Mamouni H, Fan J, Fay J, Gascon S, Gouzevitch M, Ille B, Kurca T, Lethuillier M, Mirabito L, Perries S, Alvarez JDR, Sabes D, Sgandurra L, Sordini V, Vander Donckt M, Verdier P, Viret S, Xiao H, Tsamalaidze Z, Autermann C, Beranek S, Bontenackels M, Edelhoff M, Feld L, Hindrichs O, Klein K, Ostapchuk A, Perieanu A, Raupach F, Sammet J, Schael S, Weber H, Wittmer B, Zhukov V, Ata M, Dietz-Laursonn E, Duchardt D, Erdmann M, Fischer R, Guth A, Hebbeker T, Heidemann C, Hoepfner K, Klingebiel D, Knutzen S, Kreuzer P, Merschmeyer M, Meyer A, Millet P, Olschewski M, Padeken K, Papacz R, Reithler H, Schmitz SA, Sonnenschein L, Teyssier D, Thuer S, Weber M, Cherepanov V, Erdogan Y, Flugge G, Geenen H, Geisler M, Ahmad WH, Heister A, Hoehle F, Kargoll B, Kress T, Kuessel Y, Lingemann J, Nowack A, Nugent IM, Perchalla L, Pooth O, Stahl A, Asin I, Bartosik N, Behr J, Behrenhoff W, Behrens U, Bell AJ, Bergholz M, Bethani A, Borras K, Burgmeier A, Cakir A, Calligaris L, Campbell A, Choudhury S, Costanza F, Pardos CD, Dooling S, Dorland T, Eckerlin G, Eckstein D, Eichhorn T, Flucke G, Garcia JG, Geiser A, Gunnellini R, Hauk J, Hellwig G, Hempel M, Horton D, Jung H, Kalogeropoulos A, Kasemann M, Katsas P, Kieseler J, Kleinwort C, Krucker D, Lange W, Leonard J, Lipka K, Lobanov A, Lohmann W, Lutz B, Mankel R, Marfin I, Melzer-Pellmann IA, Meyer AB, Mnich J, Mussgiller A, Naumann-Emme S, Nayak A, Novgorodova O, Nowak F, Ntomari E, Perrey H, Pitzl D, Placakyte R, Raspereza A, Cipriano PMR, Ron E, Sahin MO, Salfeld-Nebgen J, Saxena P, Schmidt R, Schoerner-Sadenius T, Schroder M, Seitz C, Spannagel S, Trevino ADRV, Walsh R, Wissing C, Martin MA, Blobel V, Vignali MC, Draeger AR, Erfle J, Garutti E, Goebel K, Gorner M, Haller J, Hoffmann M, Hoing RS, Kirschenmann H, Klanner R, Kogler R, Lange J, Lapsien T, Lenz T, Marchesini I, Ott J, Peiffer T, 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, 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, Hartmann F, Hauth T, Husemann U, Katkov I, Kornmayer A, Kuznetsova E, Pardo PL, Mozer MU, Muller T, Nurnberg A, Quast G, Rabbertz K, Ratnikov F, 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, Panagiotou A, Saoulidou N, Stiliaris E, Aslanoglou X, Evangelou I, Flouris G, Foudas C, Kokkas P, Manthos N, Papadopoulos I, Paradas E, 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, Raics P, Trocsanyi ZL, Ujvari B, Swain SK, Beri SB, Bhatnagar V, Dhingra N, Gupta R, Bhawandeep U, Kalsi AK, Kaur M, 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, Kailas S, Kumar V, Mohanty AK, Pant LM, Shukla P, Topkar A, Aziz T, Banerjee S, Bhowmik S, Chatterjee RM, Dewanjee RK, Dugad S, Ganguly S, Ghosh S, Guchait M, Gurtu A, Kole G, Kumar S, Maity M, Majumder G, Mazumdar K, Mohanty GB, Parida B, Sudhakar K, Wickramage N, Bakhshiansohi H, Behnamian H, Etesami SM, Fahim A, Goldouzian R, Jafari A, Khakzad M, Najafabadi MM, Naseri M, Mehdiabadi SP, Safarzadeh B, Zeinali M, Felcini M, Grunewald M, Abbrescia M, Barbone L, Calabria C, Chhibra SS, Colaleo A, Creanza D, De Filippis N, De Palma M, Fiore L, Iaselli G, Maggi G, Maggi M, My S, Nuzzo S, Pompili A, Pugliese G, Radogna R, Selvaggi G, Silvestris L, Singh G, Venditti R, Verwilligen P, Zito G, Abbiendi G, Benvenuti AC, Bonacorsi D, Braibant-Giacomelli S, Brigliadori L, Campanini R, Capiluppi P, Castro A, Cavallo FR, Codispoti G, Cuffiani M, Dallavalle GM, Fabbri F, Fanfani A, Fasanella D, Giacomelli P, Grandi C, Guiducci L, Marcellini S, Masetti G, Montanari A, Navarria FL, Perrotta A, Primavera F, Rossi AM, 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, Ferro F, Lo Vetere M, Robutti E, Tosi S, Dinardo ME, Dini P, 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, 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 R, Azzi P, Bacchetta N, Bisello D, Branca A, Carlin R, Checchia P, Dall'Osso M, Dorigo T, Galanti M, Gasparini F, Gasparini U, Giubilato R, Gozzelino A, Kanishchev K, Lacaprara S, Margoni M, Meneguzzo AT, Passaseo M, Pazzini J, Pozzobon N, Ronchese P, Simonetto F, Torassa E, Tosi M, Zotto P, Zucchetta A, Zumerle G, Gabusi M, Ratti SP, Riccardi C, Salvini P, Vitulo R, Biasini M, Bilei GM, Ciangottini D, Fano L, Lariccia P, Mantovani G, Menichelli M, Romeo F, Saha A, Santocchia A, Spiezia A, Androsov K, Azzurri R, Bagliesi G, Bernardini J, Boccali T, Broccolo G, Castaldi R, Ciocci MA, Dell'Orso R, Donato S, Fiori F, Foa L, Giassi A, Grippo MT, Ligabue F, Lomtadze T, Martini L, Messineo A, Moon CS, Palla F, Rizzi A, Savoy-Navarro A, Serban AT, Spagnolo P, Squillacioti P, Tenchini R, Tonelli G, Venturi A, Verdini PG, Vernieri C, Barone L, Cavallari F, D'imperio G, Del Re D, Diemoz M, Grassi M, Jorda C, Longo E, Margaroli F, Meridiani R, Micheli F, Nourbakhsh S, Organtini G, Paramatti R, Rahatlou S, Rovelli C, Santanastasio F, Soffi L, Traczyk P, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Bellan R, Biino C, Cartiglia N, Casasso S, Costa M, Degano A, Demaria N, Finco L, Mariotti C, Maselli S, Migliore E, Monaco V, Musich M, Obertino MM, Ortona G, Pacher L, Pastrone N, Pelliccioni M, Angioni GLP, Potenza A, Romero A, Ruspa M, Sacchi 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, Montanino D, Schizzi A, Umer T, Zanetti A, Kim TJ, 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 JY, Song S, Choi S, Gyun D, Hong B, Jo M, Kim H, Kim Y, Lee B, Lee KS, Park SK, Roh Y, Choi M, Kim JH, Park IC, Park S, Ryu G, Ryu MS, Choi Y, Choi YK, Goh J, Kim D, Kwon E, Lee J, Seo H, Yu I, Juodagalvis A, Komaragiri JR, Ali MABM, Castilla-Valdez H, De La Cruz-Burelo E, La Cruz IHD, Lopez-Fernandez R, Sanchez-Hernandez A, Moreno SC, Valencia FV, Pedraza I, Ibarguen HAS, Linares EC, Pineda AM, Krofcheck D, Butler PH, Reucroft S, Ahmad A, Ahmad M, Hassan Q, Hoorani HR, Khalid S, Khan WA, Khurshid T, Shah MA, 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, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Olszewski M, Wolszczak W, Bargassa P, Silva CBDE, Faccioli P, Parracho PGF, Gallinaro M, Nguyen F, Antunes JR, Seixas J, Varela J, Vischia P, Golutvin I, Karjavin V, Konoplyanikov V, Korenkov V, Kozlov G, Lanev A, Malakhov A, Matveev V, Mitsyn VV, Moisenz P, Palichik V, Perelygin V, Shmatov S, Shulha S, Skatchkov N, Smirnov V, Tikhonenko E, Zarubin A, Golovtsov V, Ivanov Y, Kim V, Levchenko P, Murzin V, Oreshkin V, Smirnov I, Sulimov V, Uvarov L, Vavilov S, Vorobyev A, Vorobyev A, Andreev Y, Dermenev A, Gninenko S, Golubev N, Kirsanov M, Krasnikov N, Pashenkov A, Tlisov D, Toropin A, Epshteyn V, Gavrilov V, Lychkovskaya N, Popov V, Safronov G, Semenov S, Spiridonov A, Stolin V, Vlasov E, Zhokin A, Epshteyn V, Gavrilov V, Lychkovskaya N, Popov V, Safronov G, Semenov S, Spiridonov A, Stolin V, Vlasov E, Zhokin A, Andreev V, Azarkin M, Dremin I, Kirakosyan M, Leonidov A, Mesyats G, Rusakov SV, Vinogradov A, Belyaev A, Boos E, Dubinin M, Dudko L, Ershov A, Gribushin A, Klyukhin V, Kodolova O, Lokhtin I, Obraztsov S, Perfilov M, Petrushanko S, Savrin V, 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, Merino G, 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, Iglesias LL, 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, Bernet C, Bianchi G, 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, Dobson M, Dordevic M, Dupont-Sagorin N, Elliott-Peisert A, Eugster J, 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, Musella P, Orsini L, Pape L, Perez E, Perrozzi L, Petrilli A, Petrucciani G, Pfeiffer A, Pierini M, 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, Treille D, Tsirou A, Veres GI, Vlimant JR, Wardle N, Wohri HK, Wollny H, Zeuner 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Measurement of the t(t)over-bar production cross section in pp collisions at root s=8 TeV in dilepton final states containing one tau lepton
PHYSICS LETTERS B 2014 DEC 12; 739(?):23-43
The top-quark pair production cross section is measured in final states with one electron or muon and one hadronically decaying tau lepton from the process t (t) over bar -> (l nu(l))(tau nu(tau))b (b) over bar, where l = e, mu. The data sample corresponds to an integrated luminosity of 19.6 fb(-1) collected with the CMS detector in proton-proton collisions at root s = 8 TeV. The measured cross section sigma(t (t) over bar) = 257 +/- 3 (stat) +/- 24 (syst) +/- 7 (lumi) pb, assuming a top-quark mass of 172.5 GeV, is consistent with the standard model prediction. (C) 2014 The Authors. Published by Elsevier B.V.
Zhou Y, Kreek MJ
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Alcohol: A stimulant activating brain stress responsive systems with persistent neuroadaptation
NEUROPHARMACOLOGY 2014 DEC; 87(?):51-58
Addictive diseases, including addiction to alcohol, opiates or cocaine, pose massive public health costs. Addictions are chronic relapsing brain diseases, caused by drug-induced direct effects and persistent neuroadaptations at the molecular, cellular and behavioral levels. These drug-type specific neuroadapations are mainly contributed by three factors: environment, including stress, the direct reinforcing effects of the drug on the CNS, and genetics. Results from animal models and basic clinical research (including human genetic study) have shown important interactions between the stress responsive systems and alcohol abuse. In this review we will discuss the involvement of the dysregulation of the stress responsive hypothalamic-pituitary-adrenal (HPA) axis in alcohol addiction (Section I). Addictions to specific drugs such as alcohol, psychostimulants and opiates (e.g., heroin) have some common direct or downstream effects on several brain stress-responsive systems, including vasopressin and its receptor system (Section II), POMC and mu opioid receptor system (Section III) and dynorphin and kappa opioid receptor systems (Section IV). Further understanding of these systems, through laboratory-based and translational studies, have the potential to optimize early interventions and to discover new treatment targets for the therapy of alcoholism. This article is part of the Special Issue entitled 'CNS Stimulants'. (C) 2014 Published by Elsevier Ltd.
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Search for supersymmetry with razor variables in pp collisions at root s=7 TeV
PHYSICAL REVIEW D 2014 DEC 1; 90(11):? Article 112001
The razor approach to search for R-parity conserving supersymmetric particles is described in detail. Two analyses are considered: an inclusive search for new heavy particle pairs decaying to final states with at least two jets and missing transverse energy, and a dedicated search for final states with at least one jet originating from a bottom quark. For both the inclusive study and the study requiring a bottom-quark jet, the data are examined in exclusive final states corresponding to all-hadronic, single-lepton, and dilepton events. The study is based on the data set of proton-proton collisions at root s = 7 TeV collected with the CMS detector at the LHC in 2011, corresponding to an integrated luminosity of 4.7 fb(-1). The study consists of a shape analysis performed in the plane of two kinematic variables, denoted M-R and R-2, that correspond to the mass and transverse energy flow, respectively, of pair-produced, heavy, new-physics particles. The data are found to be compatible with the background model, defined by studying event simulations and data control samples. Exclusion limits for squark and gluino production are derived in the context of the constrained minimal supersymmetric standard model (CMSSM) and also for simplified-model spectra (SMS). Within the CMSSM parameter space considered, squark and gluino masses up to 1350 GeV are excluded at 95% confidence level, depending on the model parameters. For SMS scenarios, the direct production of pairs of top or bottom squarks is excluded for masses as high as 400 GeV.
Kost RG, Lee LN, Yessis JL, Wesley R, Alfano S, Alexander SR, Kassis SB, Cola P, Dozier A, Ford DE, Harris PA, Kim E, Lee SC, O'Riordan G, Roth MT, Schuff K, Wasser J, Henderson DK, Coller BS
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Research Participant-Centered Outcomes at NIH-Supported Clinical Research Centers
CTS-CLINICAL AND TRANSLATIONAL SCIENCE 2014 DEC; 7(6):430-440
BackgroundAlthough research participation is essential for clinical investigation, few quantitative outcome measures exist to assess participants' experiences. To address this, we developed and deployed a survey at 15 NIH-supported clinical research centers to assess participant-centered outcomes; we report responses from 4,961 participants. MethodsSurvey questions addressed core aspects of the research participants' experience, including their overall rating, motivation, trust, and informed consent. We describe participant characteristics, responses to individual questions, and correlations among responses. ResultsRespondents broadly represented the research population in sex, race, and ethnicity. Seventy-three percent awarded top ratings to their overall research experience and 94% reported no pressure to enroll. Top ratings correlated with feeling treated with respect, listened to, and having access to the research team (R-2 = 0.80-0.96). White participants trusted researchers more (88%) than did nonwhite participants collectively (80%; p < 0.0001). Many participants felt fully prepared by the informed consent process (67%) and wanted to receive research results (72%). ConclusionsOur survey demonstrates that a majority of participants at NIH-supported clinical research centers rate their research experience very positively and that participant-centered outcome measures identify actionable items for improvement of participant's experiences, research protections, and the conduct of clinical investigation.
Cevher MA, Shi Y, Li D, Chait BT, Malik S, Roeder RG
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Reconstitution of active human core Mediator complex reveals a critical role of the MED14 subunit
NATURE STRUCTURAL & MOLECULAR BIOLOGY 2014 DEC; 21(12):1028-1034
The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to MS (CX-MS). Whereas the reconstituted head and middle modules can stably associate, basal and coactivator functions are acquired only after incorporation of MED14 into the bimodular complex. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematic dissection of the multiple layers of functionality associated with the Mediator complex.
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Identification techniques for highly boosted W bosons that decay into hadrons
JOURNAL OF HIGH ENERGY PHYSICS 2014 DEC 2; ?(12):? Article 017
In searches for new physics in the energy regime of the LHC, it is becoming increasingly important to distinguish single-jet objects that originate from the merging of the decay products of W bosons produced with high transverse momenta from jets initiated by single partons. Algorithms are defined to identify such W jets for different signals of interest, using techniques that are also applicable to other decays of bosons to hadrons that result in a single jet, such as those from highly boosted Z and Higgs bosons. The efficiency for tagging W jets is measured in data collected with the CMS detector at a center-of-mass energy of 8TeV, corresponding to an integrated luminosity of 19.7 fb(-1). The performance of W tagging in data is compared with predictions from several Monte Carlo simulators.
Hilty M, Wuthrich D, Salter SJ, Engel H, Campbell S, Sa-Leao R, de Lencastre H, Hermans P, Sadowy E, Turner P, Chewapreecha C, Diggle M, Pluschke G, McGee L, Eser OK, Low DE, Smith-Vaughan H, Endimiani A, Kuffer M, Dupasquier M, Beaudoing E, Weber J, Bruggmann R, Hanage WP, Parkhill J, Hathaway LJ, Muhlemann K, Bentley SD
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Global Phylogenomic Analysis of Nonencapsulated Streptococcus pneumoniae Reveals a Deep-Branching Classic Lineage That Is Distinct from Multiple Sporadic Lineages
GENOME BIOLOGY AND EVOLUTION 2014 DEC; 6(12):3281-3294
The surrounding capsule of Streptococcus pneumoniae has been identified as a major virulence factor and is targeted by pneumococcal conjugate vaccines (PCV). However, nonencapsulated S. pneumoniae (non-Ec-Sp) have also been isolated globally, mainly in carriage studies. It is unknown if non-Ec-Sp evolve sporadically, if they have high antibiotic nonsusceptiblity rates and a unique, specific gene content. Here, whole-genome sequencing of 131 non-Ec-Sp isolates sourced from 17 different locations around the world was performed. Results revealed a deep-branching classic lineage that is distinct from multiple sporadic lineages. The sporadic lineages clustered with a previously sequenced, global collection of encapsulated S. pneumoniae (Ec-Sp) isolates while the classic lineage is comprised mainly of the frequently identified multilocus sequences types (STs) ST344 (n = 39) and ST448 (n= 40). All ST344 and nine ST448 isolates had high nonsusceptiblity rates to beta-lactams and other antimicrobials. Analysis of the accessory genome reveals that the classic non-Ec-Sp contained an increased number of mobile elements, than Ec-Sp and sporadic non-Ec-Sp. Performing adherence assays to human epithelial cells for selected classic and sporadic non-Ec-Sp revealed that the presence of a integrative conjugative element (ICE) results in increased adherence to humanepithelial cells (P= 0.005). Incontrast, sporadic non-EcSp lacking the ICE had greater growth in vitro possibly resulting in improved fitness. In conclusion, non-Ec-Sp isolates from the classic lineage have evolved separately. They have spread globally, are well adapted to nasopharyngeal carriage and are able to coexist with Ec-Sp. Due to continued use of PCV, non-Ec-Sp may become more prevalent.