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Found 37684 matches. Displaying 3841-3850
Zhou J, Benito-Martin A, Mighty J, Chang L, Ghoroghi S, Wu H, Wong M, Guariglia S, Baranov P, Young M, Gharbaran R, Emerson M, Mark MT, Molina H, Canto-Solar MV, Selgas HP, Redenti S
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Retinal progenitor cells release extracellular vesicles containing developmental transcription factors, microRNA and membrane proteins
SCIENTIFIC REPORTS 2018 FEB 12; 8(?):? Article 2823
A range of cell types, including embryonic stem cells, neurons and astrocytes have been shown to release extracellular vesicles (EVs) containing molecular cargo. Across cell types, EVs facilitate transfer of mRNA, microRNA and proteins between cells. Here we describe the release kinetics and content of EVs from mouse retinal progenitor cells (mRPCs). Interestingly, mRPC derived EVs contain mRNA, miRNA and proteins associated with multipotency and retinal development. Transcripts enclosed in mRPC EVs, include the transcription factors Pax6, Hes1, and Sox2, a mitotic chromosome stabilizer Ki67, and the neural intermediate filaments Nestin and GFAP. Proteomic analysis of EV content revealed retinogenic growth factors and morphogen proteins. mRPC EVs were shown to transfer GFP mRNA between cell populations. Finally, analysis of EV mediated functional cargo delivery, using the Cre-loxP recombination system, revealed transfer and uptake of Cre+ EVs, which were then internalized by target mRPCs activating responder loxP GFP expression. In summary, the data supports a paradigm of EV genetic material encapsulation and transfer within RPC populations. RPC EV transfer may influence recipient RPC transcriptional and post-transcriptional regulation, representing a novel mechanism of differentiation and fate determination during retinal development.
Hetzel M, Mucci A, Blank P, Nguyen AHH, Schiller J, Halle O, Kuhnel MP, Billig S, Meineke R, Brand D, Herder V, Baumgartner W, Bange FC, Goethe R, Jonigk D, Forster R, Gentner B, Casanova JL, Bustamante J, Schambach A, Kalinke U, Lachmann N
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Hematopoietic stem cell gene therapy for IFN gamma R1 deficiency protects mice from mycobacterial infections
BLOOD 2018 FEB 1; 131(5):533-545
Mendelian susceptibility to mycobacterial disease is a rare primary immunodeficiency characterized by severe infections caused by weakly virulent mycobacteria. Biallelic null mutations in genes encoding interferon gamma receptor 1 or 2 (IFNGR1 or IFNGR2) result in a life-threatening disease phenotype in early childhood. Recombinant interferon gamma (IFN-gamma) therapy is inefficient, and hematopoietic stem cell transplantation has a poor prognosis. Thus, we developed a hematopoietic stem cell (HSC) gene therapy approach using lentiviral vectors that express Ifn gamma r1 either constitutively or myeloid specifically. Transduction of mouse Ifn gamma r1(-/-) HSCs led to stable IFN gamma R1 expression on macrophages, which rescued their cellular responses to IFN-gamma. As a consequence, genetically corrected HSC-derived macrophages were able to suppress T-cell activation and showed restored antimycobacterial activity against Mycobacterium avium and Mycobacterium bovis Bacille Calmette-Guerin (BCG) in vitro. Transplantation of genetically corrected HSCs into Ifn gamma r1(-/-) mice before BCG infection prevented manifestations of severe BCG disease and maintained lung and spleen organ integrity, which was accompanied by a reduced mycobacterial burden in lung and spleen and a prolonged overall survival in animals that received a transplant. In summary, we demonstrate an HSC-based gene therapy approach for IFN gamma R1 deficiency, which protects mice from severe mycobacterial infections, thereby laying the foundation for a new therapeutic intervention in corresponding human patients.
Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, Brandstetter J, Brondolin E, Dragicevic M, Ero J, Flechl M, Friedl M, Fruhwirth R, Ghete VM, Grossmann J, Hrubec J, Jeitler M, Konig A, Krammer N, Kratschmer I, Liko D, Madlener T, Mikulec I, Pree E, Rabady D, Rad N, Rohringer H, Schieck J, Schofbeck R, Spanring M, Spitzbart D, Waltenberger W, Wittmann J, Wulz CE, Zarucki M, Chekhovsky V, Mossolov V, Gonzalez JS, De Wolf EA, Di Croce D, Janssen X, Lauwers J, Van De Klundert M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Abu Zeid S, Blekman F, D'Hondt J, De Bruyn I, De Clercq J, Deroover K, Flouris G, Lontkovskyi D, Lowette S, Moortgat S, Moreels L, Python Q, Skovpen K, Tavernier S, Van Doninck W, Van Mulders P, Van Parijs I, Beghin D, Brun H, Clerbaux B, De Lentdecker G, Delannoy H, Dorney B, Fasanella G, Favart L, Goldouzian R, Grebenyuk A, Karapostoli G, Lenzi T, Luetic J, Maerschalk T, Marinov A, Randle-conde A, Seva T, Vander Velde C, Vanlaer P, Vannerom D, Yonamine R, Zenoni F, Zhang F, Cimmino A, Cornelis T, Dobur D, Fagot A, Gul M, Khvastunov I, Poyraz D, Roskas C, Salva S, Tytgat M, Verbeke W, Zaganidis N, Bakhshiansohi H, Bondu O, Brochet S, Bruno G, Caputo C, Caudron A, De Visscher S, Delaere C, Delcourt M, Francois B, Giammanco A, Jafari A, Komm M, Krintiras G, Lemaitre V, Magitteri A, Mertens A, Musich M, Piotrzkowski K, Quertenmont L, Marono MV, Wertz S, Beliy N, Alda WL, Alves FL, Alves GA, Brito L, Martins MC, Hensel C, Moraes A, Pol ME, Teles PR, Das Chagas EBB, Carvalho W, Chinellato J, Coelho E, Da Costa EM, Da Silveira GG, Damiao D, De Souza SF, Guativa LMH, Malbouisson H, De Almeida MM, Herrera CM, Mundim L, Nogima H, Santoro A, Sznajder A, Manganote EJT, De Araujo FTD, Pereira AV, Ahuja S, Bernardes CA, Tomei TRFP, Gregores EM, Mercadante PG, Novaes SF, Padula SS, Abad DR, Vargas JCR, Aleksandrov A, Hadjiiska R, Iaydjiev P, Misheva M, Rodozov M, Shopova M, Sultanov G, Dimitrov A, Glushkov I, Litov L, Pavlov B, Petkov P, Fang W, Gao X, Ahmad M, Bian JG, Chen GM, Chen HS, Chen M, Chen Y, Jiang CH, Leggat D, Liao H, Liu Z, Romeo F, Shaheen SM, Spiezia A, Tao J, Wang C, Wang Z, Yazgan E, Zhang H, Zhang S, Zhao J, Ban Y, Chen G, Li Q, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Avila C, Cabrera A, Sierra LFC, Florez C, Hernandez CFG, Alvarez JDR, Courbon B, Godinovic N, Lelas D, Puljak I, Cipriano PMR, Sculac T, Antunovic Z, Kovac M, Brigljevic V, Ferencek D, Kadija K, Mesic B, Starodumov A, Susa T, Ather MW, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Finger M, Finger M, Jarrin EC, Assran Y, Mahmoud MA, Mahrous A, Dewanjee RK, Kadastik M, Perrini L, Raidal M, Tiko A, Veelken C, Eerola P, Pekkanen J, Voutilainen M, Jarvinen T, Karimaki V, Kinnunen R, Lampen T, Lassila-Perini K, Lehti S, Linden T, Luukka P, Tuominen E, Tuominiemi J, Talvitie J, Tuuva T, Besancon M, Couderc F, Dejardin M, Denegri D, Faure JL, Ferri F, Ganjour S, Ghosh S, Givernaud A, Gras P, de Monchenault GH, Jarry P, Kucher I, Locci E, Machet M, Malcles J, Negro G, Rander J, Rosowsky A, Sahin MO, Titov M, Abdulsalam A, Amendola C, Antropov I, Baffioni S, Beaudette F, Busson P, Cadamuro L, Charlot C, de Cassagnac RG, Jo M, Lisniak S, Lobanov A, Blanco JM, Nguyen M, Ochando C, Ortona G, Paganini P, Pigard P, Salerno R, Sauvan JB, Sirois Y, Leiton AGS, Strebler T, Yilmaz Y, Zabi A, Zghiche A, Agram JL, Andrea J, Bloch D, Brom JM, Buttignol M, Chabert EC, Chanon N, Collard C, Conte E, Coubez X, Fontaine JC, Gele D, Goerlach U, Jansova M, Le Bihan AC, Tonon N, Van Hove P, Gadrat S, Beauceron S, Bernet C, Boudoul G, Chierici R, Contardo D, Depasse P, El Mamouni H, Fay J, Finco L, Gascon S, Gouzevitch M, Grenier G, Ille B, Lagarde F, Laktineh IB, Lethuillier M, Mirabito L, Pequegnot AL, Perries S, Popov A, Sordini V, Vander Donckt M, Viret S, Toriashvili T, Tsamalaidze Z, Autermann C, Feld L, Kiesel MK, Klein K, Lipinski M, Preuten M, Schomakers C, Schulz J, Verlage T, Zhukov V, Albert A, Dietz-Laursonn E, Duchardt D, Endres M, Erdmann M, Erdweg S, Esch T, Fischer R, Guth A, Hamer M, Hebbeker T, Heidemann C, Hoepfner K, Knutzen S, Merschmeyer M, Meyer A, Millet P, Mukherjee S, Pook T, Radziej M, Reithler H, Rieger M, Scheuch F, Teyssier D, Thuer S, Flugge G, Kargoll B, Kress T, Kunsken A, Lingemann J, Muller T, Nehrkorn A, Nowack A, Pistone C, Pooth O, Stahl A, Martin MA, Arndt T, Asawatangtrakuldee C, Beernaert K, Behnke O, Behrens U, Martinez AB, Bin Anuar AA, Borras K, Botta V, Campbell A, Connor P, Contreras-Campana C, Costanza F, Pardos CD, Eckerlin G, Eckstein D, Eichhorn T, Eren E, Gallo E, Garcia JG, Geiser A, Gizhko A, Luyando JMG, Grohsjean A, Gunnellini P, Guthoff M, Harb A, Hauk J, Hempel M, Jung H, Kalogeropoulos A, Kasemann M, Keaveney J, Kleinwort C, Korol I, Krucker D, Lange W, Lelek A, Lenz T, Leonard J, Lipka K, Lohmann W, Mankel R, Melzer-Pellmann IA, Meyer AB, Mittag G, Mnich J, Mussgiller A, Ntomari E, Pitzl D, Raspereza A, Roland B, Savitskyi M, Saxena P, Shevchenko R, Spannagel S, Stefaniuk N, Van Onsem GP, Walsh R, Wen Y, Wichmann K, Wissing C, Zenaiev O, Bein S, Blobel V, Vignali MC, Dreyer T, Garutti E, Gonzalez D, Haller J, Hinzmann A, Hoffmann M, Karavdina A, Klanner R, Kogler R, Kovalchuk N, Kurz S, Lapsien T, Marchesini I, Marconi D, Meyer M, Niedziela M, Nowatschin D, Pantaleo F, Peiffer T, Perieanu A, Scharf C, Schleper P, Schmidt A, Schumann S, Schwandt J, Sonneveld J, Stadie H, Steinbruck G, Stober FM, Stover M, Tholen H, Troendle D, Usai E, Vanelderen L, Vanhoefer A, Vormwald B, Akbiyik M, Barth C, Baur S, Butz E, Caspart R, Chwalek T, Colombo F, De Boer W, Dierlamm A, Freund B, Friese R, Giffels M, Haitz D, Hartmann F, Heindl SM, Husemann U, Kassel F, Kudella S, Mildner H, Mozer MU, Muller T, Plagge M, Quast G, Rabbertz K, Schroder M, Shvetsov I, Sieber G, Simonis HJ, Ulrich R, Wayand S, Weber M, Weiler T, Williamson S, Wohrmann C, Wolf R, Anagnostou G, Daskalakis G, Geralis T, Giakoumopoulou VA, Kyriakis A, Loukas D, Topsis-Giotis I, Karathanasis G, Kesisoglou S, Panagiotou A, Saoulidou N, Kousouris K, Evangelou I, Foudas C, Kokkas P, Mallios S, Manthos N, Papadopoulos I, Paradas E, Strologas J, Triantis FA, Csanad M, Filipovic N, Pasztor G, Veres GI, Bencze G, Hajdu C, Horvath D, Hunyadi A, Sikler F, Veszpremi V, Zsigmond AJ, Beni N, Czellar S, Karancsi J, Makovec A, Molnar J, Szillasi Z, Bartok M, Raics P, Trocsanyi ZL, Ujvari B, Choudhury S, Komaragiri JR, Bahinipati S, Bhowmik S, Mal P, Mandal K, Nayak A, Sahoo DK, Sahoo N, Swain SK, Bansal S, Beri SB, Bhatnagar V, Chawla R, Dhingra N, Kalsi AK, Kaur A, Kaur M, Kumar R, Kumari P, Mehta A, Singh JB, Walia G, Kumar A, Shah A, Bhardwaj A, Chauhan S, Choudhary BC, Garg RB, Keshri S, Kumar A, Malhotra S, Naimuddin M, Ranjan K, Sharma R, Bhardwaj R, Bhattacharya R, Bhattacharya S, Bhawandeep U, Dey S, Dutt S, Dutta S, Ghosh S, Majumdar N, Modak A, Mondal K, Mukhopadhyay S, Nandan S, Purohit A, Roy A, Roy D, Chowdhury SR, Sarkar S, Sharan M, Thakur S, Behera PK, Chudasama R, Dutta D, Jha V, Kumar V, Mohanty AK, Netrakanti PK, Pant LM, Shukla P, Topkar A, Aziz T, Dugad S, Mahakud B, Mitra S, Mohanty GB, Sur N, Sutar B, Banerjee S, Bhattacharya S, Chatterjee S, Das P, Guchait M, Jain S, Kumar S, Maity M, Majumder G, Mazumdar K, Sarkar T, Wickramage N, Chauhan S, Dube S, Hegde V, Kapoor A, Kothekar K, Pandey S, Rane A, Sharma S, Chenarani S, Tadavani EE, Etesami SM, Khakzad M, Najafabadi MM, Naseri M, Mehdiabadi SP, Hosseinabadi FR, Safarzadeh B, Zeinali M, Felcini M, Grunewald M, Abbrescia M, Calabria C, Colaleo A, Creanza D, Cristella L, De Filippis N, De Palma M, Errico F, Fiore L, Iaselli G, Lezki S, Maggi G, Maggi M, Miniello G, My S, Nuzzo S, Pompili A, Pugliese G, Radogna R, Ranieri A, Selvaggi G, Sharma A, Silvestris L, Venditti R, Verwilligen P, Abbiendi G, Battilana C, Bonacorsi D, Braibant-Giacomelli S, Campanini R, Capiluppi P, Castro A, Cavallo FR, Chhibra SS, 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, Rossi AM, Rovelli T, Siroli GP, Tosi N, Albergo S, Costa S, Di Mattia A, Giordano F, Potenza R, Tricomi A, Tuve C, Barbagli G, Chatterjee K, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Lenzi P, Meschini M, Paoletti S, Russo L, Sguazzoni G, Strom D, Viliani L, Benussi L, Bianco S, Fabbri F, Piccolo D, Primavera F, Calvelli V, Ferro F, Robutti E, Tosi S, Benaglia A, Brianza L, Brivio F, Ciriolo V, Dinardo ME, Fiorendi S, Gennai S, Ghezzi A, Govoni P, Malberti M, Malvezzi S, Manzoni RA, Menasce D, Moroni L, Paganoni M, Pauwels K, Pedrini D, Pigazzini S, Ragazzi S, Redaelli N, de Fatis TT, Buontempo S, Cavallo N, Di Guida S, Fabozzi F, Fienga F, Iorio AOM, Khan WA, Lista L, Meola S, Paolucci P, Sciacca C, Thyssen F, Azzi P, Bacchetta N, Benato L, Benettoni M, Boletti A, Carlin R, De Oliveira ACA, Checchia P, Dall'Osso M, Manzano PD, Dorigo T, Dosselli U, Gasparini F, Gasparini U, Gozzelino A, Lacaprara S, Lujan P, Margoni M, Pozzobon N, Ronchese P, Rossin R, Simonetto F, Torassa E, Ventura S, Zanetti M, Zotto P, Braghieri A, Magnani A, Montagna P, Ratti SP, Re V, Ressegotti M, Riccardi C, Salvini P, Vai I, Vitulo P, Solestizi LA, Biasini M, Bilei GM, Cecchi C, Ciangottini D, Fano L, Lariccia P, Leonardi R, Manoni E, Mantovani G, Mariani V, Menichelli M, Rossi A, Santocchia A, Spiga D, Androsov K, Azzurri P, Bagliesi G, Boccali T, Borrello L, Castaldi R, Ciocci MA, Dell'Orso R, Fedi G, Giannini L, Giassi A, Grippo MT, Ligabue F, Lomtadze T, Manca E, Mandorli G, Martini L, Messineo A, Palla F, Rizzi A, Savoy-Navarro A, Spagnolo P, Tenchini R, Tonelli G, Venturi A, Verdini PG, Barone L, Cavallari F, Cipriani M, Daci N, Del Re D, Di Marco E, Diemoz M, Gelli S, Longo E, Margaroli F, Marzocchi B, Meridiani P, Organtini G, Paramatti R, Preiato F, Rahatlou S, Rovelli C, Santanastasio F, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Bartosik N, Bellan R, Biino C, Cartiglia N, Cenna F, Costa M, Covarelli R, Degano A, Demaria N, Kiani B, Mariotti C, Maselli S, Migliore E, Monaco V, Monteil E, Monteno M, Obertino MM, Pacher L, Pastrone N, Pelliccioni M, Angioni GLP, Ravera F, Romero A, Ruspa M, Sacchi R, Shchelina K, Sola V, Solano A, Staiano A, Traczyk P, Belforte S, Casarsa M, Cossutti F, Della Ricca G, Zanetti A, Kim DH, Kim GN, Kim MS, Lee J, Lee S, Lee SW, Moon CS, Oh YD, Sekmen S, Son DC, Yang YC, Lee A, Kim H, Moon DH, Oh G, Cifuentes JAB, Goh J, Kim TJ, Cho S, Choi S, Go Y, Gyun D, Ha S, Hong B, Jo Y, Kim Y, Lee K, Lee KS, Lee S, Lim J, Park SK, Roh Y, Almond J, Kim J, Kim JS, Lee H, Lee K, Nam K, Oh SB, Radburn-Smith BC, Seo SH, Yang UK, Yoo HD, Yu GB, Choi M, Kim H, Kim JH, Lee JSH, Park IC, Choi Y, Hwang C, Lee J, Yu I, Dudenas V, Juodagalvis A, Vaitkus J, Ahmed I, Ibrahim ZA, Ali MABM, Idris FM, Abdullah WATW, Yusli MN, Zolkapli Z, Reyes-Almanza R, Ramirez-Sanchez G, Duran-Osuna MC, Castilla-Valdez H, De la Cruz-Burelo E, Heredia-De la Cruz I, Rabadan-Trejo RI, Lopez-Fernandez R, Guisao JM, Sanchez-Hernandez A, Moreno SC, Barrera CO, Valencia FV, Pedraza I, Ibarguen HAS, Estrada CU, Pineda AM, Krofcheck D, Butler PH, Ahmad A, Ahmad M, Hassan Q, Hoorani HR, Saddique A, Shah MA, Shoaib M, Waqas M, Bialkowska H, Bluj M, Boimska B, Frueboes T, Gorski M, Kazana M, Nawrocki K, Szleper M, Zalewski P, Bunkowski K, Byszuk A, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Olszewski M, Pyskir A, Walczak M, Bargassa P, Silva CBE, Di Francesco A, Faccioli P, Galinhas B, Gallinaro M, Hollar J, Leonardo N, Iglesias LL, Nemallapudi MV, Seixas J, Strong G, Toldaiev O, Vadruccio D, Varela J, Baginyan A, Golunov A, Golutvin I, Karjavin V, Korenkov V, Kozlov G, Lanev A, Malakhov A, Matveev V, Mitsyn VV, Palichik V, Perelygin V, Shmatov S, Smirnov V, Voytishin N, Yuldashev BS, Zarubin A, Zhiltsov V, Ivanov Y, Kim V, Kuznetsova E, Levchenko P, Murzin V, Oreshkin V, Smirnov I, Sulimov V, Uvarov L, Vavilov S, Vorobyev A, Andreev Y, Dermenev A, Gninenko S, Golubev N, Karneyeu A, Kirsanov M, Krasnikov N, Pashenkov A, Tlisov D, Toropin A, Epshteyn V, Gavrilov V, Lychkovskaya N, Popov V, Pozdnyakov I, Safronov G, Spiridonov A, Stepennov A, Toms M, Vlasov E, Zhokin A, Aushev T, Bylinkin A, Chadeeva M, Parygin P, Philippov D, Polikarpov S, Popova E, Rusinov V, Rusinov V, Azarkin M, Dremin I, Kirakosyan M, Terkulov A, Baskakov A, Belyaev A, Boos E, Ershov A, Gribushin A, Khein L, Klyukhin V, Kodolova O, Lokhtin I, Lukina O, Miagkov I, Obraztsov S, Petrushanko S, Savrin V, Snigirev A, Blinov V, Shtol D, Skovpen Y, Azhgirey I, Bayshev I, Bitioukov S, Elumakhov D, Kachanov V, Kalinin A, Konstantinov D, Petrov V, Ryutin R, Sobol A, Troshin S, Sobol A, Tyurin N, Uzunian A, Volkov A, Adzic P, Cirkovic P, Devetak D, Dordevic M, Milosevic J, Rekovic V, Maestre JA, Luna MB, Cerrada M, Colino N, De la Cruz B, Peris AD, Del Valle AE, Bedoya CF, Ramos JPF, Flix J, Fouz MC, Garcia-Abia P, Lopez OG, Lopez SG, Hernandez JM, Josa MI, Moran D, Yzquierdo APC, Pelayo JP, Olmeda AQ, Redondo I, Romero L, Soares MS, Fernandez AA, Albajar C, de Troconiz JF, Missiroli M, Cuevas J, Erice C, Menendez JF, Caballero IG, Fernandez JRG, Cortezon EP, Cruz SS, Vischia P, Garcia JMV, Cabrillo IJ, Calderon A, Quero BC, Curras E, Campderros JD, Fernandez M, Garcia-Ferrero J, Gomez G, Virto AL, Marco J, Rivero CM, del Arbol PMR, Matorras F, Gomez JP, Rodrigo T, Ruiz-Jimeno A, Scodellaro L, Trevisani N, Vila I, Cortabitarte RV, Abbaneo D, Auffray E, Baillon P, Ball AH, Barney D, Bianco M, Bloch P, Bocci A, Botta C, Camporesi T, Castello R, Cepeda M, Cerminara G, Chapon E, Chen Y, d'Enterria D, Dabrowski A, Daponte V, David A, De Gruttola M, De Roeck A, Dobson M, du Pree T, Dunser M, Dupont N, Elliott-Peisert A, Everaerts P, Fallavollita F, Franzoni G, Fulcher J, Funk W, Gigi D, Gilbert A, Gill K, Glege F, Gulhan D, Harris P, Hegeman J, Innocente V, Janot P, Karacheban O, Kieseler J, Kirschenmann H, Knunz V, Kornmayer A, Kortelainen MJ, Krammer M, Lange C, Lecoq P, Lourenco C, Lucchini MT, Malgeri L, Mannelli M, Martelli A, Meijers F, Merlin JA, Mersi S, Meschi E, Milenovic P, Moortgat F, Mulders M, Neugebauer H, Ngadiuba J, Orfanelli S, Orsini L, Pape L, Perez E, Peruzzi M, Petrilli A, Petrucciani G, Pfeiffer A, Pierini M, Racz A, Reis T, Rolandi G, Rovere M, Sakulin H, Schafer C, Schwick C, Seidel M, Selvaggi M, Sharma A, Silva P, Sphicas P, Stakia A, Steggemann J, Stoye M, Tosi M, Treille D, Triossi A, Tsirou A, Veckalns V, Verweij M, Zeuner WD, Bertl W, Caminada L, Deiters K, Erdmann W, Horisberger R, Ingram Q, Kaestli HC, Kotlinski D, Langenegger U, Rohe T, Wiederkehr SA, Bani L, Berger P, Bianchini L, Casal B, Dissertori G, Dittmar M, Donegaa M, Grab C, Heidegger C, Hits D, Hoss J, Kasieczka G, Klijnsma T, Lustermann W, Mangano B, Marionneau M, Meinhard MT, Meister D, Micheli F, Musella P, Nessi-Tedaldi F, Pandolfi F, Pata J, Pauss F, Perrin G, Perrozzi L, Quittnat M, Reichmann M, 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Constraintson the double-parton scattering cross section from same-sign W boson pair production in proton-proton collisions at root s=8TeV
JOURNAL OF HIGH ENERGY PHYSICS 2018 FEB 6; ?(2):? Article 032
A first search for same-sign WW production via double-parton scattering is performed based on proton-proton collision data at a center-of-mass energy of 8TeV using dimuon and electron-muon final states. The search is based on the analysis of data corresponding to an integrated luminosity of 19.7 fb(-1). No significant excess of events is observed above the expected single-parton scattering yields. A 95% confidence level upper limit of 0.32 pb is set on the inclusive cross section for same-sign WW production via the double-parton scattering process. This upper limit is used to place a 95% confidence level lower limit of 12.2mb on the effective double-parton cross section parameter, closely related to the transverse distribution of partons in the proton. This limit on the effective cross section is consistent with previous measurements as well as with Monte Carlo event generator predictions.
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Measurements of the pp -> ZZ production cross section and the Z -> 4l branching fraction, and constraints on anomalous triple gauge couplings at root s=13TeV
EUROPEAN PHYSICAL JOURNAL C 2018 FEB 24; 78(2):? Article 165
Four-lepton production in proton-proton collisions, pp -> (Z/gamma*)(Z/gamma*) -> 4l, where l = e or mu, is studied at a center-of-mass energy of 13 TeV with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb(-1). The ZZ production cross section, sigma(pp -> ZZ) = 17.2 +/- 0.5 (stat) +/- 0.7 (syst) +/- 0.4 (theo) +/- 0.4 (lumi) pb, measured using events with two opposite-sign, same-flavor lepton pairs produced in the mass region 60 < m(l+l-) < 120 GeV, is consistent with standard model predictions. Differential cross sections are measured and are well described by the theoretical predictions. The Z boson branching fraction to four leptons is measured to be B(Z -> 4l) = 4.83(-0.22)(+0.23) (stat)(-0.29)(+0.32) (syst) +/- 0.08 (theo) +/- 0.12(lumi) x 10(-6) for events with a four-lepton invariant mass in the range 80 < m(4l) < 100 GeV and a dilepton mass m(ll) > 4GeV for all opposite-sign, same-flavor lepton pairs. The results agree with standard model predictions. The invariant mass distribution of the four-lepton system is used to set limits on anomalous ZZZ and ZZ. couplings at 95% confidence level: -0.0012 < f(4)(Z) < 0.0010, -0.0010 < f(5)(Z) < 0.0013, -0.0012 < f(4)(gamma) < 0.0013, -0.0012 < f(5)(gamma) < 0.0013.
Conde-Ocazionez S, Altavini TS, Wunderle T, Schmidt KE
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Motion contrast in primary visual cortex: a direct comparison of single neuron and population encoding
EUROPEAN JOURNAL OF NEUROSCIENCE 2018 FEB; 47(4):358-369
Features from outside the classical receptive field (CRF) can modulate the stimulus-driven activity of single cells in the primary visual cortex. This modulation, mediated by horizontal and feedback networks, has been extensively described as a variation of firing rate and is considered the basis of processing features as, for example, motion contrast. However, surround influences have also been identified in pairwise spiking or local field coherence. Yet, evidence about co-existence and integration of different neural signatures remains elusive. To compare multiple signatures, we recorded spiking and LFP activity evoked by stimuli exhibiting a motion contrast in the CRFs surround in anesthetized cat primary visual cortex. We chose natural-like scenes over gratings to avoid predominance of simple visual features, which could be easily represented by a rate code. We analyzed firing rates and phase-locking to low-gamma frequency in single cells and neuronal assemblies. Motion contrast was reflected in all measures but in semi-independent populations. Whereas activation of assemblies accompanied single neuron rates, their phase relations were modulated differently. Interestingly, only assembly phase relations mirrored the direction of movement of the surround and were selectively affected by thermal deactivation of visual interhemispheric connections. We argue that motion contrast can be reflected in complementary and superimposed neuronal signatures that can represent different surround features in independent neuronal populations.
Hasegawa Y, Ikeda K, Chen Y, Alba DL, Stifler D, Shinoda K, Hosono T, Maretich P, Yang YY, Ishigaki Y, Chi JY, Cohen P, Koliwad SK, Kajimura S
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Repression of Adipose Tissue Fibrosis through a PRDM16-GTF2IRD1 Complex Improves Systemic Glucose Homeostasis
CELL METABOLISM 2018 JAN 9; 27(1):180-194.e6
Adipose tissue fibrosis is a hallmark of malfunction that is linked to insulin resistance and type 2 diabetes; however, what regulates this process remains unclear. Here we show that the PRDM16 transcriptional complex, a dominant activator of brown/beige adipocyte development, potently represses adipose tissue fibrosis in an uncoupling protein 1 (UCP1)-independent manner. By purifying the PRDM16 complex, we identified GTF2IRD1, a member of the TFII-I family of DNA-binding proteins, as a cold-inducible transcription factor that mediates the repressive action of the PRDM16 complex on fibrosis. Adipocyte-selective expression of GTF2IRD1 represses adipose tissue fibrosis and improves systemic glucose homeostasis independent of body-weight loss, while deleting GTF2IRD1 promotes fibrosis in a cell-autonomous manner. GTF2IRD1 represses the transcription of transforming growth factor beta-dependent pro-fibrosis genes by recruiting PRDM16 and EHMT1 onto their promoter/enhancer regions. These results suggest a mechanism by which repression of obesity-associated adipose tissue fibrosis through the PRDM16 complex leads to an improvement in systemic glucose homeostasis.
Chen ZL, Notti RQ, Ueberheide B, Ruthenburg AJ
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Quantitative and Structural Assessment of Histone Methyllysine Analogue Engagement by Cognate Binding Proteins Reveals Affinity Decrements Relative to Those of Native Counterparts
BIOCHEMISTRY 2018 JAN 23; 57(3):300-304
Methyllysine analogues (MLAs), furnished by aminoethylation of engineered cysteine residues, are widely used surrogates of histone methyllysine and are considered to be effective proxies for studying these epigenetic marks in vitro. Here we report the first structure of a trimethyllysine MLA histone in complex with a protein binding partner, quantify the thermodynamic distinctions between MLAs and their native methyllysine counterparts, and demonstrate that these differences can compromise qualitative interpretations of binding at the nucleosome level. Quantitative measurements with two methyllysine binding protein modules reveal substantial affinity losses for the MLA peptides versus the corresponding native methyllysine species in both cases, although the thermodynamic underpinnings are distinct. MLA and methyllysine adopt distinct conformational geometries when in complex with the BPTF PHD finger, a well-established H3K4me3 binding partner. In this case, an similar to 13-fold K-d difference at the peptide level translates to nucleosomal affinities for MLA analogues that fall outside of the detectable range in a pull-down format, whereas the methyllysine species installed by native chemical ligation demonstrates robust binding. Thus, despite their facile production and commercial availability, there is a significant caveat of potentially altered binding affinity when MLAs are used in place of native methyllysine residues.
Durrieu-Gaillard S, Dumay-Odelot H, Boldina G, Tourasse NJ, Allard D, Andre F, Macari F, Choquet A, Lagarde P, Drutel G, Leste-Lasserre T, Petitet M, Lesluyes T, Lartigue-Faustin L, Dupuy JW, Chibon F, Roeder RG, Joubert D, Vagner S, Teichmann M
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Regulation of RNA polymerase III transcription during transformation of human IMR90 fibroblasts with defined genetic elements
CELL CYCLE 2018; 17(5):605-615
RNA polymerase (Pol) III transcribes small untranslated RNAs that are essential for cellular homeostasis and growth. Its activity is regulated by inactivation of tumor suppressor proteins and overexpression of the oncogene c-MYC, but the concerted action of these tumor-promoting factors on Pol III transcription has not yet been assessed. In order to comprehensively analyse the regulation of Pol III transcription during tumorigenesis we employ a model system that relies on the expression of five genetic elements to achieve cellular transformation. Expression of these elements in six distinct transformation intermediate cell lines leads to the inactivation of TP53, RB1, and protein phosphatase 2A, as well as the activation of RAS and the protection of telomeres by TERT, thereby conducting to full tumoral transformation of IMR90 fibroblasts. Transformation is accompanied by moderately enhanced levels of a subset of Pol III-transcribed RNAs (7SK; MRP; H1). In addition, mRNA and/or protein levels of several Pol III subunits and transcription factors are upregulated, including increased protein levels of TFIIIB and TFIIIC subunits, of SNAPC1 and of Pol III subunits. Strikingly, the expression of POLR3G and of SNAPC1 is strongly enhanced during transformation in this cellular transformation model. Collectively, our data indicate that increased expression of several components of the Pol III transcription system accompanied by a 2-fold increase in steady state levels of a subset of Pol III RNAs is sufficient for sustaining tumor formation.
Brivanlou AH
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Human Embryonic Stem Cells in Development PREFACE
HUMAN EMBRYONIC STEM CELLS IN DEVELOPMENT 2018; 129(?):XI-XIII
Johnson ZL, Chen J
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ATP Binding Enables Substrate Release from Multidrug Resistance Protein 1
CELL 2018 JAN 11; 172(1-2):81-89.e10
The multidrug resistance protein MRP1 is an ATP-driven pump that confers resistance to chemotherapy. Previously, we have shown that intracellular substrates are recruited to a bipartite binding site when the transporter rests in an inward-facing conformation. A key question remains: how are high-affinity substrates transferred across the membrane and released outside the cell? Using electron cryomicroscopy, we show here that ATP binding opens the transport pathway to the extracellular space and reconfigures the substrate-binding site such that it relinquishes its affinity for substrate. Thus, substrate is released prior to ATP hydrolysis. With this result, we now have a complete description of the conformational cycle that enables substrate transfer in a eukaryotic ABC exporter.