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Found 37769 matches. Displaying 6301-6310
Delgado-Olguin P, Dang LT, He D, Thomas S, Chi LJ, Sukonnik T, Khyzha N, Dobenecker MW, Fish JE, Bruneau BG
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Ezh2-mediated repression of a transcriptional pathway upstream of Mmp9 maintains integrity of the developing vasculature
DEVELOPMENT 2014 DEC; 141(23):4610-4617
Maintenance of vascular integrity is required for embryogenesis and organ homeostasis. However, the gene expression programs that stabilize blood vessels are poorly understood. Here, we show that the histone methyltransferase Ezh2 maintains integrity of the developing vasculature by repressing a transcriptional program that activates expression of Mmp9. Inactivation of Ezh2 in developing mouse endothelium caused embryonic lethality with compromised vascular integrity and increased extracellular matrix degradation. Genome-wide approaches showed that Ezh2 targets Mmp9 and its activators Fosl1 and Klf5. In addition, we uncovered Creb3l1 as an Ezh2 target that directly activates Mmp9 gene expression in the endothelium. Furthermore, genetic inactivation of Mmp9 rescued vascular integrity defects in Ezh2-deficient embryos. Thus, epigenetic repression of Creb3l1, Fosl1, Klf5 and Mmp9 by Ezh2 in endothelial cells maintains the integrity of the developing vasculature, potentially linking this transcriptional network to diseases with compromised vascular integrity.
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.
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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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, Jafari A, Komm PJM, 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 TDR, Herrera CM, Pol ME, Carvalho W, Chinellato J, Custodio A, 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, Liu S, Mao Y, Qian SJ, Teng H, Wang D, 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, 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, Charlot C, Dahms T, Dalchenko M, Dobrzynski L, Filipovic N, Florent A, 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, Guichardant C, Ille B, Kurca T, Lethuillier M, Mirabito L, Perries S, Alvarez JDR, Sabes D, Sgandurra L, Sordini V, Donckt MV, 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, Brodski M, Dietz-Laursonn E, Duchardt D, Erdmann M, Fischer R, Guth A, Hebbeker T, Heidemann C, Hoepfner K, Klingebiel D, Knutzen S, Kreuzer P, Mer-Schmeyer M, Meyer A, Millet P, Olschewski M, Padeken K, Papacz P, 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, Choud-Hury S, Costanza F, Pardos CD, Dooling S, Dorland T, Eckerlin G, Eckstein D, Eichhorn T, Flucke G, Garcia JG, Geiser A, Gunnellini P, Hauk J, 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, Mittag G, Mnich J, Mussgiller A, Naumann-Emme S, Nayak A, Novgorodova O, 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, 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, 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 J, 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, 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, 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, Khakzad M, Najafabadi MM, Naseri M, Mehdiabadi SP, Hosseinabadi FR, 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, 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, Bisello D, Branca A, Carlin R, Checchia P, Dall'Osso M, Galanti M, Gasparini F, Gasparini U, Giubilato P, Gozzelino A, Kanishchev K, Meneguzzo AT, Montecassiano F, Passaseo M, Pazzini J, Pegoraro M, Pozzobon N, Simonetto F, Torassa E, Tosi M, Triossi A, Ventura S, Zotto P, Zucchetta A, Zumerle G, Gabusi M, Ratti SP, Riccardi C, Salvini P, Vitulo P, 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 P, 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 P, 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, 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, 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, Heredia-de La Cruz I, 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, Afanasiev S, Bunin P, Golutvin I, Gorbunov I, Karjavin V, Konoplyanikov V, Kozlov G, Lanev A, Malakhov A, Matveev V, Moisenz P, Palichik V, Perelygin V, Shmatov S, Shulha S, Skatchkov N, Smirnov V, 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, 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, Kaminskiy A, Klyukhin V, Kodolova O, Lokhtin I, Obraztsov S, 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 J, Battilana C, Calvo E, Cerrada M, Llatas M, Colino N, De la Cruz B, Peris A, 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, 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I, Kangal EE, Topaksu AK, Onengut G, Ozdemir K, Ozturk S, Polatoz A, Cerci DS, Tali B, Topakli H, Vergili M, Akin IV, Bilin B, Bilmis S, Gamsizkan H, Karapinar G, Ocalan K, Sekmen S, Surat UE, Yalvac M, Zeyrek M, Gulmez E, Isildak B, Kaya M, Kaya O, Cankocak K, Vardarli FI, Levchuk L, Sorokin P, Brooke JJ, Clement E, Cussans D, Flacher H, Frazier R, Goldstein J, Grimes M, Heath GP, Heath HF, Jacob J, Kreczko L, Lucas C, Meng Z, Newbold DM, Paramesvaran S, Poll A, Senkin S, Smith VJ, Williams T, 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, Womersley WJ, Worm SD, Baber M, Bainbridge R, Buchmuller O, Burton D, Colling D, Cripps N, Cutajar M, Dauncey P, Davies G, Della Negra M, Dunne P, Ferguson W, Fulcher J, Futyan D, Gilbert A, 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, Martin W, Reid ID, Symonds P, Teodorescu L, Turner M, Dittmann J, Hatakeyama K, Kasmi A, Liu H, Scarborough T, Charaf O, Cooper SI, Henderson C, Rumerio P, Avetisyan A, Bose T, Fantasia C, Lawson P, Richardson C, Rohlf J, St John J, Sulak L, Alimena J, Berry E, Bhattacharya S, Christopher G, Cutts D, Demiragli Z, Dhingra N, Ferapontov A, Garabedian A, Heintz U, Kukartsev G, Laird E, Landsberg G, Luk M, Narain M, Segala M, 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, Miceli T, Mulhearn M, Pellett D, Pilot J, Ricci-Tam F, Searle M, 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, Nguyen H, Negrete MO, Shrinivas A, Sumowidagdo S, Wimpenny S, Andrews W, Branson JG, Cerati GB, Cittolin S, D'Agnolo RT, Evans D, Holzner A, Kelley R, Klein D, Lebourgeois M, Letts J, Macneill I, Olivito D, Padhi S, Palmer C, Pieri M, Sani M, Sharma V, Simon S, Sudano E, Tadel M, Tu Y, Vartak A, Welke C, Wurthwein F, Yagil A, Yoo J, Barge D, Bradmiller-Feld J, Campagnari C, Danielson T, Dishaw A, Flowers K, Sevilla MF, Geffert P, George C, Golf F, Gouskos L, Incandela J, Justus C, Mccoll N, Richman J, Stuart D, To W, West C, Apresyan A, Bornheim A, Bunn J, Chen Y, Di Marco E, Duarte J, Mott A, Newman HB, Pena C, Rogan C, Spiropulu M, Timciuc V, 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, Lopez EL, Nauenberg U, Smith JG, Stenson K, Ulmer KA, Wagner SR, Alexander J, Chatterjee A, 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, Burkett K, Butler JN, Cheung HWK, Chlebana F, Cihangir S, Elvira VD, Fisk I, Freeman J, Gao Y, Gottschalk E, Gray L, Green D, Grunendahl S, Gutsche O, Hanlon J, Hare D, Harris RM, Hirschauer J, Hooberman B, Jindariani S, Johnson M, Joshi U, Kaadze K, Klima B, Kreis B, Kwan S, Linacre J, Lincoln D, Lipton R, Liu T, Lykken J, Maeshima K, Marraffino JM, Outschoorn VIM, Maruyama S, Mason D, McBride P, Mishra K, Mrenna S, Musienko Y, Nahn S, Newman-Holmes C, O'Dell V, Prokofyev O, Sexton-Kennedy E, Sharma S, 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, Cheng T, 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, 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 T, Askew A, Bochenek J, Diamond B, Haas J, Hagopian S, Hagopian V, Baarmand MM, Hohlmann M, Kalakhety H, Yumiceva F, Adams MR, Apanasevich L, Bazterra VE, Berry D, Betts RR, Bucinskaite I, Cavanaugh R, Evdokimov O, Gauthier L, Gerber CE, Hofman DJ, Khalatyan S, Kurt P, Moon DH, O'Brien C, Silkworth C, Turner P, Varelas N, Albayrak EA, Bilki B, Clarida W, Dilsiz K, Duru F, Haytmyradov M, Merlo JP, 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, Yetkin T, Yi K, Barnett BA, Blumenfeld B, Bolognesi S, Fehling D, Gritsan AV, Maksimovic P, Martin C, Osherson M, Swartz M, Xin Y, Baringer P, Bean A, Benelli G, Bruner C, Kenny RP, Malek M, Murray M, Noonan D, Sanders S, Sekaric J, Stringer R, Wang Q, Wood JS, Barfuss AF, Chakaberia I, Ivanov A, Khalil S, Makouski M, Maravin Y, Saini LK, Shrestha S, Skhirtladze N, Svintradze I, Gronberg J, Lange D, Rebassoo F, Wright D, Baden A, Belloni A, Calvert B, Eno SC, Gomez JA, Hadley NJ, Kellogg RG, Kolberg T, Lu Y, Marionneau M, Mignerey AC, Pedro K, Skuja A, Tonjes MB, Tonwar SC, Apyan A, Barbieri R, Bauer G, Busza W, Cali IA, Chan M, Di Matteo L, Dutta V, Ceballos GG, Goncharov M, Gulhan D, Klute M, Lai YS, Lee YJ, Levin A, Luckey PD, Ma T, Paus C, Ralph D, Roland C, Roland G, Stephans GSF, Stockli F, 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, Pastika N, 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, Malik S, Meier F, Snow GR, Dolen J, Godshalk A, Iashvili I, Kharchilava A, Kumar A, Rappoccio S, Alverson G, Barberis E, Baumgartel D, Chasco M, Haley J, 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, Luo W, Lynch S, Marinelli N, Pearson T, Planer M, Ruchti R, Valls N, Wayne M, Wolf M, Woodard A, Antonelli L, Brinson J, Bylsma B, Durkin LS, Flowers S, Hill C, Hughes R, Kotov K, Ling TY, Puigh D, Rodenburg M, Smith G, Winer BL, Wolfe H, Wulsin HW, Driga O, Elmer P, Hebda P, Hunt A, 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, Mendez H, Vargas JER, Barnes VE, Benedetti D, Bolla G, Bortoletto D, De Mattia M, Hu Z, Jha MK, Jones M, Jung K, Kress M, Leonardo N, Pegna DL, Maroussov V, Merkel P, Miller DH, Neumeister N, Radburn-Smith BC, Shi X, Shipsey I, Silvers D, Svyatkovskiy A, Wang F, Xie W, Xu L, Yoo HD, Zablocki J, Zheng Y, 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, Covarelli R, de Barbaro P, Demina R, Eshaq Y, Ferbel T, Garcia-Bellido A, Goldenzweig P, Han J, Harel A, Khukhunaishvili A, Petrillo G, Vishnevskiy D, Ciesielski R, Demortier L, Goulianos K, Lungu G, 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, Patel R, Salur S, Schnetzer S, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Rose K, Spanier S, York A, Bouhali O, Hernandez AC, Eusebi R, Flanagan W, Gilmore J, Kamon T, Khotilovich V, Krutelyov V, Montalvo R, Osipenkov I, Pakhotin Y, Perloff A, Roe J, Rose A, Safonov A, Sakuma T, Suarez I, Tatarinov A, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero PR, 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, 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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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.
Lu CC, Wu TS, Hsu YJ, Chang CJ, Lin CS, Chia JH, Wu TL, Huang TT, Martel J, Ojcius DM, Young JD, Lai HC
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NK cells kill mycobacteria directly by releasing perforin and granulysin
JOURNAL OF LEUKOCYTE BIOLOGY 2014 DEC; 96(6):1119-1129
NK cells directly kill mycobacteria through a contactdependent mechanism leading to the release of perforin and granulysin. Although the mechanisms underlying the cytotoxic effect of NK cells on tumor cells and intracellular bacteria have been studied extensively, it remains unclear how these cells kill extracellular bacterial pathogens. In this study, we examine how human NK cells kill Mycobacterium kansasii and M.tb. The underlying mechanism is contact dependent and requires two cytolytic proteins: perforin and granulysin. Mycobacteria induce enhanced expression of the cytolytic proteins via activation of the NKG2D/NCR cell-surface receptors and intracellular signaling pathways involving ERK, JNK, and p38 MAPKs. These results suggest that NK cells use similar cellular mechanisms to kill both bacterial pathogens and target host cells. This report reveals a novel role for NK cells, perforin, and granulysin in killing mycobacteria and highlights a potential alternative defense mechanism that the immune system can use against mycobacterial infection.
Zaaijer ER, Bruijel J, Blanken P, Hendriks V, Koeter MWJ, Kreek MJ, Booij J, Goudriaan AE, van Reec JM, van den Brink W
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Personality as a risk factor for illicit opioid use and a protective factor for illicit opioid dependence
DRUG AND ALCOHOL DEPENDENCE 2014 DEC 1; 145(?):101-105
Background: Most studies investigating the role of personality as a risk factor for the development of opioid dependence compare dependent opioid users with healthy controls who never used heroin. In order to understand the potential protective role of personality, it is crucial to compare illicit opioid users who never became dependent with dependent opioid users. Aims: This study aims to examine the role of personality as a risk factor for opioid use and as a protective factor for the development of opioid dependence. Methods: Comparing personality factors between three groups: (1) 161 never-dependent illicit opioid users who have been using illicit opioids but never became opioid dependent; (2) 402 dependent opioid users in methadone maintenance treatment or heroin-assisted treatment; and (3) 135 healthy controls who never used heroin. Personality was assessed with a short version of Cloninger's Temperament and Character Inventory. Results: Never-dependent opioid users reported more Novelty Seeking and Harm Avoidance and less Self-Directedness and Cooperativeness than healthy controls and more Reward Dependence and Self-Directedness, and less Harm Avoidance than dependent opioid users. Furthermore, never-dependent opioid users reported more Self-Transcendence than both dependent opioid users and healthy controls. Conclusions: Never-dependent opioid users may have started to use opioids partly due to their tendency to seek novel and/or spiritual experiences (high Novelty Seeking, high Self-Transcendence) and their tendency to avoid aversive stimuli (high Harm Avoidance), whereas they may have been protected against the development of dependence by their need for social approval (high Reward Dependence) and their self-efficacy (high Self-Directedness). (C) 2014 Elsevier Ireland Ltd. All rights reserved.
Kim E, Wang Y, Kim SJ, Bornhorst M, Jecrois ES, Anthony TE, Wang CR, Li YE, Guan JL, Murphy GG, Zhu Y
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Transient inhibition of the ERK pathway prevents cerebellar developmental defects and improves long-term motor functions in murine models of neurofibromatosis type 1
ELIFE 2014 DEC 23; 3(?):?
Individuals with neurofibromatosis type 1 (NF1) frequently exhibit cognitive and motor impairments and characteristics of autism. The cerebellum plays a critical role in motor control, cognition, and social interaction, suggesting that cerebellar defects likely contribute to NF1-associated neurodevelopmental disorders. Here we show that Nf1 inactivation during early, but not late stages of cerebellar development, disrupts neuronal lamination, which is partially caused by overproduction of glia and subsequent disruption of the Bergmann glia (BG) scaffold. Specific Nf1 inactivation in glutamatergic neuronal precursors causes premature differentiation of granule cell (GC) precursors and ectopic production of unipolar brush cells (UBCs), indirectly disrupting neuronal migration. Transient MEK/ERK inhibition during a neonatal window prevents cerebellar developmental defects and improves long-term motor performance of Nf1-deficient mice. This study reveals essential roles of Nf1 in GC/UBC migration by generating correct numbers of glia and controlling GC/UBC fate-specification/differentiation, identifying a therapeutic prevention strategy for multiple NF1-associcated developmental abnormalities.
Westcott NP, Hang HC
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Chemical reporters for exploring ADP-ribosylation and AMPylation at the host-pathogen interface
CURRENT OPINION IN CHEMICAL BIOLOGY 2014 DEC; 23(?):56-62
Bacterial pathogens secrete protein toxins and effectors that hijack metabolites to covalently modify host proteins and interfere with their function during infection. Adenosine metabolites, such as nicotinamide adenine dinucleotide (NAD) and adenosine triphosphate (ATP), have in particular been co-opted by these secreted virulence factors to reprogram host pathways. While some host targets for secreted virulence factors have been identified, other toxin and effector substrates have been elusive, which require new methods for their characterization. In this review, we focus on chemical reporters based on NAD and ATP that should facilitate the discovery and characterization of adenosine diphosphate (ADP)-ribosylation and adenylylation/AMPylation in bacterial pathogenesis and cell biology.
Wen DC, Noh KM, Goldberg AD, Allis CD, Rosenwaks Z, Rafii S, Banaszynski LA
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Genome Editing a Mouse Locus Encoding a Variant Histone, H3.3B, to Report on its Expression in Live Animals
GENESIS 2014 DEC; 52(12):959-966
Chromatin remodeling via incorporation of histone variants plays a key role in the regulation of embryonic development. The histone variant H3.3 has been associated with a number of early events including formation of the paternal pronucleus upon fertilization. The small number of amino acid differences between H3.3 and its canonical counterparts (H3.1 and H3.2) has limited studies of the developmental significance of H3.3 deposition into chromatin due to difficulties in distinguishing the H3 isoforms. To this end, we used zinc-finger nuclease (ZFN) mediated gene editing to introduce a small C-terminal hemagglutinin (HA) tag to the endogenous H3.3B locus in mouse embryonic stem cells (ESCs), along with an internal ribosome entry site (IRES) and a separately translated fluorescent reporter of expression. This system will allow detection of expression driven by the reporter in cells, animals, and embryos, and will facilitate investigation of differential roles of paternal and maternal H3.3 protein during embryogenesis that would not be possible using variant-specific antibodies. Further, the ability to monitor endogenous H3.3 protein in various cell lineages will enhance our understanding of the dynamics of this histone variant over the course of development. genesis 52:959-966, 2014. (c) 2014 Wiley Periodicals, Inc.
Forgacs PB, Conte MM, Fridman EA, Voss HU, Victor JD, Schiff ND
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Preservation of Electroencephalographic Organization in Patients with Impaired Consciousness and Imaging-Based Evidence of Command-Following
ANNALS OF NEUROLOGY 2014 DEC; 76(6):869-879
ObjectiveStandard clinical characterization of patients with disorders of consciousness (DOC) relies on observation of motor output and may therefore lead to the misdiagnosis of vegetative state or minimally conscious state in patients with preserved cognition. We used conventional electroencephalographic (EEG) measures to assess a cohort of DOC patients with and without functional magnetic resonance imaging (fMRI)-based evidence of command-following, and correlated the findings with standard clinical behavioral evaluation and brain metabolic activity. MethodsWe enrolled 44 patients with severe brain injury. Behavioral diagnosis was established using standardized clinical assessments. Long-term EEG recordings were analyzed to determine wakeful background organization and presence of elements of sleep architecture. A subset of patients had fMRI testing of command-following using motor imagery paradigms (26 patients) and resting brain metabolism measurement using (18)fluorodeoxyglucose positron emission tomography (31 patients). ResultsAll 4 patients with fMRI evidence of covert command-following consistently demonstrated well-organized EEG background during wakefulness, spindling activity during sleep, and relative preservation of cortical metabolic activity. In the entire cohort, EEG organization and overall brain metabolism showed no significant association with bedside behavioral testing, except in a few cases when EEG was severely abnormal. InterpretationThese findings suggest that conventional EEG is a simple strategy that complements behavioral and imaging characterization of DOC patients. Preservation of specific EEG features may be used to assess the likelihood of unrecognized cognitive abilities in severely brain-injured patients with very limited or no motor responses. Ann Neurol 2014;76:869-879