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Found 37173 matches. Displaying 5041-5050
Park M, Sivertsen BB, Els-Heindl S, Huber T, Holst B, Beck-Sickinger AG, Schwartz TW, Sakmar TP
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Bioorthogonal Labeling of Ghrelin Receptor to Facilitate Studies of Ligand-Dependent Conformational Dynamics
CHEMISTRY & BIOLOGY 2015 NOV 19; 22(11):1431-1436
Ghrelin receptor (GhrR) is a promising drug target because of its central role in energy homeostasis. GhrR, known for high constitutive activity, is thought to display multi-state conformations during activation and signaling. We used genetically encoded unnatural amino acids and bioorthogonal labeling reactions to engineer multiple fluorescent donor-acceptor pairs to probe ligand-directed structural changes in GhrR. We demonstrate how conformational dynamics of a G-protein-coupled receptor can be measured in reconstituted systems.
Chandramouly G, McDevitt S, Sullivan K, Kent T, Luz A, Glickman JF, Andrake M, Skorski T, Pomerantz RT
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Small-Molecule Disruption of RAD52 Rings as a Mechanism for Precision Medicine in BRCA-Deficient Cancers
CHEMISTRY & BIOLOGY 2015 NOV 19; 22(11):1491-1504
Suppression of RAD52 causes synthetic lethality in BRCA-deficient cells. Yet pharmacological inhibition of RAD52, which binds single-strand DNA (ssDNA) and lacks enzymatic activity, has not been demonstrated. Here, we identify the small molecule 6-hydroxy-DL-dopa (6-OH-dopa) as a major allosteric inhibitor of the RAD52 ssDNA binding domain. For example, we find that multiple small molecules bind to and completely transform RAD52 undecamer rings into dimers, which abolishes the ssDNA binding channel observed in crystal structures. 6-OH-Dopa also disrupts RAD52 heptamer and undecamer ring superstructures, and suppresses RAD52 recruitment and recombination activity in cells with negligible effects on other double-strand break repair pathways. Importantly, we show that 6-OH-dopa selectively inhibits the proliferation of BRCA-deficient cancer cells, including those obtained from leukemia patients. Taken together, these data demonstrate small-molecule disruption of RAD52 rings as a promising mechanism for precision medicine in BRCA-deficient cancers.
Kang HC, Baek ST, Song S, Gleeson JG
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Clinical and Genetic Aspects of the Segmental Overgrowth Spectrum Due to Somatic Mutations in PIK3CA
JOURNAL OF PEDIATRICS 2015 NOV; 167(5):957-962
Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, Brandstetter J, Brondolin E, Dragicevic M, Ero J, Flechl M, Friedl M, Fruhwirth R, Ghete VM, Hartl C, Hormann N, Hrubec J, Jeitler M, Knunz V, Konig A, Krammer M, Kratschmer I, Liko D, Matsushita T, Mikulec I, Rabady D, Rahbaran B, Rohringer H, Schieck J, Schofbeck R, Strauss J, Treberer-Treberspurg W, Waltenberger W, Wulz CE, Mossolov V, Shumeiko N, Gonzalez JS, Alderweireldt S, Cornelis T, De Wolf EA, Janssen X, Knutsson A, Lauwers J, Luyckx S, Ochesanu S, Rougny R, Van De Klundert M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Van Spilbeeck A, Abu Zeid S, Blekman F, D'Hondt J, Daci N, De Bruyn I, Deroover K, Heracleous N, Keaveney J, Lowette S, Moreels L, Olbrechts A, Python Q, Strom D, Tavernier S, Van Doninck W, Van Mulders P, Van Onsem GP, Van Parijs I, Barria P, Caillol C, Clerbaux B, De Lentdecker G, Delannoy H, Fasanella G, Favart L, Gay APR, Grebenyuk A, Karapostoli G, Lenzi T, Leonard A, Maerschalk T, Marinov A, Pernie L, Randle-Conde A, Reis T, Seva T, Velde CV, Vanlaer P, Yonamine R, Zenoni F, Zhang F, Beernaert K, Benucci L, Cimmino A, Crucy S, Dobur D, Fagot A, Garcia G, Gul M, Mccartin J, Rios AAO, Poyraz D, Ryckbosch D, Salva S, Sigamani M, Strobbe N, Tytgat M, Van Driessche W, Yazgan E, Zaganidis N, Basegmez S, Beluffi C, Bondu O, Brochet S, Bruno G, Castello R, Caudron A, Ceard L, Da Silveira GG, Delaere C, Favart D, Forthomme L, Giammanco A, Hollar J, Jafari A, Jez P, Komm M, Lemaitre V, Mertens A, Nuttens C, Perrini L, Pin A, Piotrzkowski K, Popov A, Quertenmont L, Selvaggi M, Marono MV, Beliy N, Hammad GH, Alda WL, Alves GA, Brito L, Martins MC, Hamer M, Hensel C, Herrera CM, Moraes A, Pol ME, Teles PR, Das Chagas EBB, Carvalho W, Chinellato J, Custodio A, Da Costa EM, Damiao DD, Martins CD, De Souza SF, Guativa LMH, Malbouisson H, Figueiredo DM, Mundim L, Nogima H, Da Silva WLP, Santoro A, Sznajder A, Manganote EJT, Vereira AV, Ahuja S, Bernardes CA, Santos AD, Dogra S, Tomei TRFP, Gregores EM, Mercadante PC, Moon CS, Novaes SF, Padula SS, Abad DR, Vargas JCR, Aleksandrov A, Genchev V, Hadjiiska R, Iaydjiev P, Rodozov M, Stoykova S, Sultanov G, Vutova M, Dimitrov A, Glushkov I, Litov L, Pavlov B, Petkov P, Ahmad M, Bian JG, Chen GM, Chen HS, Chen M, Cheng T, Du R, Jiang CH, Plestina R, Romeo F, Shaheen SM, Tao J, Wang C, Wang Z, Zhang H, Asawatangtrakuldee C, Ban Y, Li Q, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Zou W, Avila C, Cabrera A, Sierra LFC, Florez C, Gomez JP, Moreno BG, Sanabria JC, Godinovic N, Lelas D, Polic D, Puljak I, Cipriano PMR, Antunovic Z, Kovac M, Brigljevic V, Kadija K, Luetic J, Micanovic S, Sudic L, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Bodlak M, Finger M, Finger M, Abdelalim AA, Awad A, Mahrous A, Radi A, Calpas B, Kadastik M, Murumaa M, Raidal M, Tiko A, Veelken C, Eerola P, Pekkanen J, Voutilainen M, Harkonen J, Karimaki V, Kinnunen R, 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, Machet M, Malces J, Rander J, Rosowsky A, Titov M, Zghiche A, Antropov I, Baffioni S, Beaudette F, Busson P, Cadamuro L, Chapon E, Charlot C, Dahms T, Davignon O, Filipovic N, Florent A, de Cassagnac RG, Lisniak S, Mastrolorenzo L, Mine P, Naranjo IN, Nguyen M, Ochando C, Ortona G, Paganini P, Regnard S, Salerno R, Sauvan JB, Sirois Y, Strebler T, Yilmaz Y, Zabi A, Agram JL, Andrea J, Aubin A, Bloch D, Brom JM, Buttignol M, Chabert EC, Chanon N, Collard C, Conte E, Coubez X, Fontaine JC, Gele D, Goerlach U, Goetzmann C, Le Bihan AC, Merlin JA, Skovpen K, Van Hove P, Gadrat S, Beauceron S, Bernet C, Boudoul G, Bouvier E, Montoya CAC, Chasserat J, Chierici R, Contardo D, Courbon B, Depasse P, El Mamouni H, Fan J, Fay J, Gascon S, Gouzevitch M, Ille B, Lagarde F, Laktineh IB, Lethuillier M, Mirabito L, Pequegnot AL, Perries S, Alvarez JDR, Sabes D, Sgandurra L, Sordini V, Donckt MV, Verdier P, Viret S, Xiao H, Toriashvili T, Tsamalaidze Z, Autermann C, Beranek S, Edelhoff M, Feld L, Heister A, Kiesel MK, Klein K, Lipinski M, Ostapchuk A, Preuten M, Raupach F, Schael S, Schulte JF, Verlage T, Weber H, Wittmer B, Zhukov V, Ata M, Brodski M, Dietz-Laursonn E, Duchardt D, Endres M, Erdmann M, Erdweg S, Esch T, 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 P, Pook T, Radziej M, Reithler H, Rieger M, Scheuch F, Sonnenschein L, Teyssier D, Thuer S, Cherepanov V, Erdogan Y, Flugge G, Geenen H, Geisler M, Hoehle F, Kargoll B, Kress T, Kuessel Y, Kunsken A, Lingemann J, Nehrkorn A, Nowack A, Nugent IM, Pistone C, Pooth O, Stahl A, Martin MA, Asin I, Bartosik N, Behnke O, Behrens U, Bell AJ, Borras K, Burgmeier A, Cakir A, Calligaris L, Campbell A, Choudhury S, Costanza F, Pardos CD, Dolinska G, Dooling S, Dorland T, Eckerlin G, Eckstein D, Eichhorn T, Flucke G, Gallo E, Garcia JG, Geiser A, Gizhko A, Gunnellini P, Hauk J, Hempel M, Jung H, Kalogeropoulos A, Karacheban O, Kasemann M, Katsas P, Kieseler J, Kleinwort C, Korol I, Lange W, Leonard J, Lipka K, Lobanov A, Lohmann W, Mankel R, Marfin I, Melzer-Pellmann IA, Meyer AB, Mittag G, Mnich J, Mussgiller A, Naumann-Emme S, Nayak A, Ntomari E, Perrey H, Pitzl D, Placakyte R, Raspereza A, Roland B, Sahin MO, Saxena P, Schoerner-Sadenius T, Schroder M, Seitz C, Spannagel S, Trippkewitz KD, Walsh R, Wissing C, Blobel V, Vignali MC, Draeger AR, Erfle J, Garutti E, Goebel K, Gonzalez D, Gorner M, Haller J, Hoffmann M, Hoing RS, Junkes A, Klanner R, Kogler R, Lapsien T, Lenz T, Marchesini I, Marconi D, Meyer M, Nowatschin D, Ott J, Pantaleo F, Peiffer T, Perieanu A, Pietsch N, Poehlsen J, Rathjens D, Sander C, Schettler H, Schleper P, Schlieckau E, Schmidt A, Schwandt J, Seidel M, Sola V, Stadie H, Steinbruck G, Tholen H, Troendle D, Usai E, Vanelderen L, Vanhoefer A, Vormwald B, Akbiyik M, Barth C, Baus C, Berger J, Boser C, Butz E, Chwalek T, Colombo F, De Boer W, Descroix A, Dierlamm A, Fink S, Frensch F, Giffels M, Gilbert A, Hartmann F, Heindl SM, Husemann U, Katkov I, Kornmayer A, Pardo PL, Maier B, Mildner H, Mozer MU, Muller T, Muller T, Plagge M, Quast G, Rabbertz K, Rocker S, Roscher F, Simonis HJ, Stober FM, Ulrich R, Wagner-Kuhr J, Wayand S, Weber M, Weiler T, Wohrmann C, Wolf R, Anagnostou G, Daskalakis G, Geralis T, Giakoumopoulou VA, Kyriakis A, Loukas D, Psallidas A, Topsis-Giotis I, Agapitos A, Kesisoglou S, Panagiotou A, Saoulidou N, Tziaferi E, Evangelou I, Flouris G, Foudas C, Kokkas P, Loukas N, Manthos N, Papadopoulos I, Paradas E, Strologas J, Bencze G, Hajdu C, Hazi A, Hidas P, Horvath D, Sikler F, Veszpremi V, Vesztergombi G, Zsigmond AJ, Beni N, Czellar S, Karancsi J, Molnar J, Szillasi Z, Bartok M, Makovec A, Raics P, Trocsanyi ZL, Ujvari B, Mal P, Mandal K, Sahoo N, Swain SK, Bansal S, Beri SB, Bhatnagar V, Chawla R, Gupta R, Bhawandeep U, Kalsi AK, Kaur A, Kaur M, Kumar R, Mehta A, Mittal M, Singh JB, Walia G, Kumar A, Kumar A, Bhardwaj A, Choudhary BC, Garg RB, Kumar A, Malhotra S, Naimuddin M, Nishu N, Ranjan K, Sharma R, Sharma V, Banerjee S, Bhattacharya S, Chatterjee K, Dey S, Dutta S, Jain S, Majumdar N, Modak A, Mondal K, Mukherjee S, Mukhopadhyay S, Roy A, Roy D, Chowdhury SR, Sarkar S, Sharan M, Abdulsalam A, Chudasama R, Dutta D, Jha V, 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, Mahakud B, Maity M, Majumder G, Mazumdar K, Mitra S, Mohanty GB, Parida B, Sarkar T, Sudhakar K, Sur N, Sutar B, Wickramage N, Chauhan S, Dube S, Sharma S, 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, Calabria C, Caputo C, Chhibra SS, Colaleo A, Creanza D, Cristella L, De Filippis N, De Palma M, Fiore L, Iaselli G, Maggi G, Maggi M, Miniello G, My S, Nuzzo S, Pompili A, Pugliese G, Radogna R, Ranieri A, Selvaggi G, Silvestris L, Venditti R, Verwilligen P, Abbiendi G, Battilana C, 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, Marcellinia S, Masetti G, Montanari A, Navarria FL, Perrotta A, Rossi AM, Rovelli T, Siroli GP, Tosi N, Travaglini R, 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, Goilzi S, Gori V, Lenzi P, Meschini M, Paoletti S, Sguazzoni G, Tropiano A, Viliani L, Benussi L, Bianco S, Fabbri F, Piccolo D, Calvelli V, Ferro F, Lo Vetere M, Monge MR, Robutti E, Tosi S, Brianza L, Dinardo ME, Fiorendi S, Gennai S, Gerosa R, Ghezzi A, Govoni P, Malvezzi S, Manzoni RA, Marzocchi B, Menasce D, Moroni L, Paganoni M, Pedrini D, Ragazzi S, Redaelli N, de Fatis TT, Buontempo S, Cavallo N, Di Guida S, Esposito M, Fabozzi F, Iorio AOM, Lanza G, Lista L, Meola S, Merola M, Paolucci P, Sciacca C, Thyssen F, Azzi P, Bacchetta N, Benato L, Bisello D, Boletti A, Carlin R, De Oliveira ACA, Checchia P, Dall'Osso M, Dorigo T, Dosselli U, Gasparini F, Gasparini U, Gonella F, Gozzelino A, Lacaprara S, Margoni M, Meneguzzo AT, Montecassiano F, Pazzini J, Pozzobon N, Ronchese P, Simonetto F, Torassa E, Tosi M, Zanetti M, Zotto P, Zucchetta A, Zumerle G, Braghieri A, Magnani A, Montagna P, Ratti SP, Re V, Riccardi C, Salvini P, Vai I, Vitulo P, Solestizi LA, Biasini M, Bilei GM, Ciangottini D, Fano L, Lariccia P, Mantovani G, Menichelli M, 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, Fedi G, Foa L, Giassi A, Grippo MT, Ligabue F, Lomtadze T, Martini L, Messineo A, Palla F, Rizzi A, Savoy-Navarro A, Serban AT, Spagnolo P, Squillacioti P, Tenchini R, Tonelli G, Venturi A, Verdini PC, Barone L, Cavallari F, D'imperio G, Del Re D, Diemoz M, Gelli S, Jorda C, Longo E, Margaroli F, Meridiani P, Micheli F, Organtini G, Paramatti R, Preiato F, Rahatlou S, Rovellli C, Santanastasio F, Traczyk P, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Bellan R, Biino C, Cartiglia N, Costa M, Covarelli R, Degano A, Dellacasa G, Demaria N, Finco L, Kiani B, Mariotti C, Maselli S, Migliore E, Monaco V, Monteil E, Musich M, Obertino MM, Pacher L, Pastrone N, Pelliccioni M, Angioni GLP, Ravera F, Romero A, Ruspa M, Sacchi R, Solano A, Staiano A, Belforte S, Candelise V, Casarsa M, Cossutti F, Della Ricca G, Gobbo B, La Licata C, Marone M, Schizzi A, Umer T, Zanetti A, Chang S, Kropivnitskaya A, Nam SK, Kim DH, Kim GN, Kim MS, Kong DJ, Lee S, Oh YD, Sakharov A, Son DC, Cifuentes JAB, Kim H, Kim TJ, Ryu MS, Song S, Choi S, Go Y, Gyun D, Hong B, Jo M, Kim H, Kim Y, Lee B, Lee K, Lee KS, Lee S, Park SK, Roh Y, Yoo HD, Choi M, Kim H, Kim JH, Lee JSH, Park IC, Ryu G, Choi Y, Choi YK, Goh J, Kim D, Kwon E, Lee J, Yu I, Juodagalvis A, Vaitkus J, Ahmed I, Ibrahim ZA, Komaragiri JR, Ai MABM, Idris FM, Abdullah WATW, Yusli MN, Linares EC, Castilla-Valdez H, De la Cruz-Burelo E, La Cruz IHD, Hernandez-Almada A, Lopez-Fernandez R, Sanchez-Hernandez A, Moreno SC, Valencia FV, Pedraza I, Ibarguen HAS, Pineda AM, Krofcheck D, Krofcheck D, Reucroft S, Ahmad A, Ahmad M, Hassan Q, Hoorani HR, Khan WA, Khurshid T, Shoaib M, Bialkowska H, Bluj M, Boimska B, Frueboes T, Gorski M, Kazana M, Nawrocki K, Romanowska-Rybinska K, Szleper M, Zalewski P, Brona G, Bunkowski K, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Olszewski M, Walczak M, Bargassa P, Silva CBDE, Di Francesco A, Faccioli P, Parracho PCF, Gallinaro M, Leonardo N, Iglesias LL, Nguyen F, Antunes JR, Seixas J, Toldaiev O, Vadruccio O, Varela J, Vischia P, Afanasiev S, Bunin P, Gavrilenko M, Golutvin I, Gorbunov I, Kamenev A, Karjavin V, Konoplyanikov V, Laney 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, 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, Vlasov E, Zhokin A, Bylinkin A, Andreev V, Azarkin M, Dremin I, Kirakosyan M, Leonidov A, Mesyats G, Rusakov SV, Vinogradov A, Baskakov A, Belyaev A, Boos E, Dubinin M, Dudko L, Ershov A, Gribushin A, Klyukhin V, Kodolova O, Lokhtin I, Myagkov I, Obraztsov S, Petrushanko S, Savrin V, Snigirev A, Azhgirey I, Bayshev I, Bitioukov S, Kachanov V, Kalinin A, Konstantinov D, Krychkine V, Petrov V, Ryutin R, Sobol A, Tourtchanovitch L, Troshin S, Tyurin N, Uzunian A, Volkov A, Adzic P, Ekmedzic M, Milosevic J, Rekovic V, Maestre JA, Calvo E, Cerrada M, Llatas MC, Colino N, De La Cruz B, Peris AD, Vazquez DD, Del Valle AE, Bedoya CF, Ramos JPF, Flix J, Fouz MC, Garcia-Abia P, Lopez OG, Lopez SG, Hernandez JM, Josa MI, De Martino EN, Yzquierdo APC, Pelayo JP, Olmeda AQ, Redondo I, Romero L, Soares MS, Albajar C, de Troconiz JF, Missiroli M, Moran D, Brun H, Cuevas J, Menendez JF, Folgueras S, Caballero IG, Cortezon EP, Garcia JMV, Cabrillo IJ, Calderon A, De Saa JRC, Manzano PD, Campderros JD, Fernandez M, Garcia-Ferrero J, 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, Berruti GM, Bloch P, Bocci A, Bonato A, Botta C, Breuker H, Camporesi T, Cerminara G, Colafranceschi S, D'Alfonso M, d'Enterria D, Dabrowski A, Daponte V, David A, De Gruttola M, De Guio F, De Roeck A, De Visscher S, Di Marco E, Dobson M, Dordevic M, Dorney B, du Pree T, Dupont N, Elliott-Peisert A, Franzoni G, Funk W, Gigi D, Gill K, Giordano D, Girone M, Glege F, Guida R, Gundacker S, Guthoff M, Hammer J, Harris P, Hegeman J, Innocente V, Janot P, Kirschenmann H, Kortelainen MJ, Kousouris K, Krajczar K, Lecoq P, Lourenco C, Lucchini MT, Magini N, Malgeri L, Mannelli M, Martelli A, Masetti L, Meijers F, Mersi S, Meschi E, Moortgat F, Morovic S, Mulders M, Nemallapudi MV, Neugebauer H, Orfanelli S, Orsini L, Pape L, Perez E, Petrilli A, Petrucciani G, Pfeiffer A, Piparo D, Racz A, Rolandi G, Rovere M, Ruan M, Sakulin H, Schafer C, Schwick C, Sharma A, Silva P, Simon M, Sphicas P, Spiga D, Steggemann J, Stieger B, Stoye M, Takahashi Y, Treille D, Triossi A, Tsirou A, Veres GI, Wardle N, Wohri HK, Zagozdzinska A, Zeuner WD, Bertl W, Deiters K, Erdmann W, Horisberger R, Ingram Q, Kaestli HC, Kotlinski D, Langenegger U, Renker D, Rohe T, Bachmair F, Bani L, Bianchini L, Buchmann MA, Casal B, Dissertori G, Dittmar M, Donega M, Dunser M, Eller P, Grab C, Heidegger C, Hits D, Hoss J, Kasieczka G, Lustermann W, Mangano B, Marini AC, Marionneau M, del Arbol PMR, Masciovecchio M, Meister D, Musella P, Nessi-Tedaldi F, Pandolfi F, Pata J, Pauss F, Perrozzi L, Peruzzi M, Quittnat M, Rossini M, Starodumov A, Takahashi M, Tavolaro VR, Theofilatos K, Wallny R, Aarrestad TK, Amsler C, Caminada L, Canelli MF, Chiochia V, De Cosa A, Galloni C, Hinzmann A, Hreus T, Kilminster B, Lange C, Ngadiuba J, Pinna D, Robmann P, Ronga FJ, Salerno D, Yang Y, Cardaci M, Chen KH, Doan TH, Jain S, Khurana R, Konyushikhin M, Kuo CM, Lin W, Lu YJ, Volpe R, Yu SS, Bartek R, Chang P, Chang YH, Chang YW, Chao Y, Chen KF, Chen PH, Dietz C, Fiori F, Grundler U, Hou WS, Hsiung Y, Liu YF, Lu RS, Moya MM, Petrakou E, Tsai JF, Tzeng YM, Asavapibhop B, Kovitanggoon K, Singh G, Srimanobhas N, Suwonjandee N, Adiguzel A, Bakirci MN, Demiroglu ZS, Dozen C, Dumanoglu I, Eskut E, Girgis S, Gokbulut G, Guler Y, Gurpinar E, Hos I, Kangal EE, Topaksu AK, Onengut G, Ozdemir K, Polatoz A, Cerci DS, Vergili M, Zorbilmez C, Akin IV, Bilin B, Bilmis S, Isildak B, Karapinar G, Surat UE, Yalvac M, Zeyrek M, Albayrak EA, Gulmez E, Kaya M, Kaya O, Yetkin T, Cankocak K, Sen S, Vardarli FI, Grynyov B, Levchuk L, Sorokin P, Aggleton R, Ball F, Beck L, Brooke JJ, Clement E, Cussans D, Flacher H, Goldstein J, Grimes M, Heath GP, Heath HF, Jacob J, Kreczko L, Lucas C, Meng Z, Newbold DM, Paramesvaran S, Poll A, Sakuma T, El Nasr-Storey SS, Senkin S, Smith D, Smith VJ, Bell KW, Belyaev A, Brew C, Brown RM, Cockerill DJA, Coughlan JA, Harder K, Harper S, Olaiya E, Petyt D, Shepherd-Themistocleous CH, Thea A, Thomas L, Tomalin IR, Williams T, Womersley WJ, Worm SD, Baber M, Bainbridge R, Buchmuller O, Bundock A, Burton D, Casasso S, Citron M, Colling D, Corpe L, Cripps N, Dauncey P, Davies G, De Wit A, Della Negra M, Dunne P, Elwood A, Ferguson W, Fulcher J, Futyan D, Hall G, Iles G, Kenzie M, Lane R, Lucas R, Lyons L, Magnan AM, Malik S, Nash J, Nikitenko A, Pela J, Pesaresi M, Petridis K, Raymond DM, Richards A, Rose A, Seez C, Tapper A, Uchida K, Acosta MV, Virdee T, Zenz SC, Cole JE, Hobson PR, Khan A, Kyberd P, Leggat D, Leslie D, Reid ID, Symonds P, Teodorescu L, Turner M, Borzou A, Call K, Dittmann J, Hatakeyama K, Kasmi A, Liu H, Pastika N, Charaf O, Cooper SI, Henderson C, Rumerio P, Avetisyan A, Bose T, Fantasia C, Gastler D, Lawson P, Rankin D, Richardson C, Rohlf J, St John J, Sulak L, Zou D, Alimena J, Berry E, Bhattacharya S, Cutts D, Dhingra N, Ferapontov A, Garabedian A, Heintz U, Laird E, Landsberg G, Mao Z, Narain M, Piperov S, Sagir S, Sinthuprasith T, Syarif R, Breedon R, Breto G, Sanchez MCD, Chauhan S, Chertok M, Conway J, Conway R, Cox PT, Erbacher R, Gardner M, Ko W, Lander R, Mulhearn M, Pellett D, Pilot J, Ricci-Tam F, Shalhout S, Smith J, Squires M, Stolp D, Tripathi M, Wilbur S, Yohay R, Cousins R, Everaerts P, Farrell C, Hauser J, Ignatenko M, Saltzberg D, Takasugi E, Valuev V, Weber M, Burt K, Clare R, Ellison J, Gary JW, Hanson G, Heilman J, Paneva MI, Jandir P, Kennedy E, Lacroix F, Long OR, Luthra A, Malberti M, Negrete MO, Shrinivas A, Wei H, Wimpenny S, Branson JG, Cerati GB, Cittolin S, D'Agnolo RT, Holzner A, Kelley R, Klein D, Letts J, Macneill I, Olivito D, Padhi S, Pieri M, Sani M, Sharma V, Simon S, Tadel M, Vartak A, Wasserbaech S, Welke C, Wurthwein F, Yagil A, Della Porta GZ, Barge D, Bradmiller-Feld J, Campagnari C, Dishaw A, Dutta V, Flowers K, Sevilla MF, Geffert P, George C, Golf F, Gouskos L, Gran J, Incandela J, Justus C, Mccoll N, Mullin SD, Richman J, Stuart D, Suarez I, To W, West C, Yoo J, Anderson D, Apresyan A, Bornheim A, Bunn J, Chen Y, Duarte J, Mott A, Newman HB, Pena C, Pierini M, Spiropulu M, Vlimant JR, Xie S, Zhu RY, Azzolini V, Calamba A, Carlson B, Ferguson T, Paulini M, Russ J, Sun M, Vogel H, Vorobiev I, Cumalat JP, Ford WT, Gaz A, Jensen F, Johnson A, Krohn M, Mulholland T, Nauenberg U, Stenson K, Wagner SR, Alexander J, Chatterjee A, Chaves J, Chu J, Dittmer S, Eggert N, Mirman N, Kaufman GN, Patterson JR, Rinkevicius A, Ryd A, Skinnari L, Soffi L, Sun W, Tan SM, Teo WD, Thom J, Thompson J, Tucker J, Weng Y, Wittich P, Abdullin S, Albrow M, Anderson J, Apollinari G, Bauerdick LAT, Beretvas A, Berryhill J, Bhat PC, Bolla G, Burkett K, Butler JN, Cheung HWK, Chlebana F, Cihangir S, Elvira VD, Fisk I, Freeman J, Gottschalk E, Gray L, Green D, Grunendahl S, Gutsche O, Hanlon J, Hare D, Harris RM, Hirschauer J, Hooberman B, Hu Z, Jindariani S, Johnson M, Joshi U, Jung AW, Klima B, Kreis B, Kwan S, Lammel S, Linacre J, Lincoln D, Lipton R, Liu T, De Sa RL, Lykken J, Maeshima K, Marraffino JM, Outschoorn VIM, Maruyama S, Mason D, McBride P, Merkel P, Mishra K, Mrenna S, Nahn S, Newman-Holmes C, O'Dell V, Pedro K, Prokofyev O, Rakness G, Sexton-Kennedy E, Soha A, Spalding WJ, Spiegel L, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vernieri C, Verzocchi M, Vidal R, Weber HA, Whitbeck A, Yang F, Yin H, Acosta D, Avery P, Bortignon P, Bourilkov D, Carnes A, Carver M, Curry D, Das S, Di Giovanni GP, Field RD, Fisher M, Furic IK, Hugon J, Konigsberg J, Korytov A, Low JF, Ma P, Matchev K, Mei H, Milenovic P, Mitselmakher G, Muniz L, Rank D, Rossin R, Shchutska L, Snowball M, Sperka D, Wang J, Wang S, Yelton J, Hewamanage S, Linn S, Markowitz P, Martinez G, Rodriguez JL, Ackert A, Adams JR, Adams T, Askew A, Bochenek J, Diamond B, Haas J, Hagopian S, Hagopian V, Johnson KF, Khatiwada A, Prosper H, Veeraraghavan V, Weinberg M, Bhopatkar V, Hohlmann M, Kalakhety H, Mareskas-palcek D, Roy T, Yumiceva F, Adams MR, Apanasevich L, Berry D, Betts RR, Bucinskaite I, Cavanaugh R, Evdokimov O, Gauthier L, Gerber CE, Hofman DJ, Kurt P, O'Brien C, Gonzalez IDS, Silkworth C, Turner P, Varelas N, Wu Z, Zakaria M, Bilki B, Clarida W, Dilsiz K, Durgut S, Gandrajula RP, Haytmyradov M, Khristenko V, Merlo JP, Mermerkaya H, Mestvirishvili A, Moeller A, Nachtman J, Ogul H, Onel Y, Ozok F, Penzo A, Snyder C, Tan P, Tiras E, Wetzel J, Yi K, Anderson I, Barnett BA, Blumenfeld B, Fehling D, Feng L, Gritsan AV, Maksimovie P, Martin C, Osherson M, Swartz M, Xiao M, Xin Y, You C, Baringer P, Bean A, Benelli G, Bruner C, Gray J, Kenny RP, Majumder D, Malek M, Murray M, Noonan D, Sanders S, Stringer R, Wang Q, Wood JS, Chakaberia I, Ivanov A, Kaadze K, Khalil S, Makouski M, Maravin Y, Mohammadi A, Saini LK, Skhirtladze N, Svintradze I, Toda S, Lange D, Rebassoo F, Wright D, Anelli C, Baden A, Baron O, Belloni A, Calvert B, Eno SC, Ferraioli C, Gomez JA, Hadley NJ, Jabeen S, Kellogg RG, Kolberg T, Kunkle J, Lu Y, Mignerey AC, Shin YH, Skuja A, Tonjes MB, Tonwar SC, Apyan A, Barbieri R, Baty A, Bierwagen K, Brandt S, Busza W, Cali IA, Demiragli Z, Di Matteo L, Ceballos GG, Goncharov M, Gulhan D, Iiyama Y, Innocenti GM, Klute M, Kovalskyi D, Lai YS, Lee YJ, Levin A, Luckey PD, Mcginn C, Mironov C, Niu X, Paus C, Ralph D, Roland C, Roland G, Salfeld-Nebgen J, Stephans GSF, Sumorok K, Varma M, Velicanu D, Veverka J, Wang J, Wang TW, Wyslouch B, Yang M, Zhukova V, Dahmes B, Finkel A, Gude A, Hansen P, Kalafut S, Kao SC, Klapoetke K, Kubota Y, Lesko Z, Mans J, Nourbakhsh S, Ruckstuhl N, Rusack R, Tambe N, Turkewitz J, Acosta JG, Oliveros S, Avdeeva E, Bloom K, Bose S, Claes DR, Dominguez A, Fangmeier C, Suarez RG, Kamalieddin R, Keller J, Knowlton D, Kravchenko I, Lazo-Flores J, Meier F, Monroy J, Ratnikov F, Siado JE, Snow GR, Alyari M, Dolen J, George J, Godshalk A, Iashvili I, Kaisen J, Kharchilava A, Kumar A, Rappoccio S, Alverson G, Barberis E, Baumgartel D, Chasco M, Hortiangtham A, Knapp B, Massironi A, Morse DM, Nash D, Orimoto T, De Lima RT, 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, Trovato M, Velasco M, Brinkerhoff A, Dev N, Hildreth M, Jessop C, Karmgard DJ, Kellams N, Lannon K, Lynch S, Marinelli N, Meng F, Mueller C, Musienko Y, Pearson T, Planer M, Reinsvold A, Ruchti R, Smith G, Taroni S, Valls N, Wayne M, Wolf M, Woodard A, Antonelli L, Brinson J, Bylsma B, Durkin LS, Flowers S, Hart A, Hill C, Hughes R, Kotov K, Ling TY, Liu B, Luo W, Puigh D, Rodenburg M, Winer BL, Wulsin HW, Driga O, Elmer P, Hardenbrook J, Hebda P, Koay SA, Lujan P, Marlow D, Medvedeva T, Mooney M, Olsen J, Palmer C, Piroue P, Quan X, Saka H, Land DS, Tully C, Werner JS, Zuranski A, Malik S, Barnes VE, Benedetti D, Bortoletto D, Gutay L, Jha MK, Jones M, Jung K, Kress M, Miller DH, Neumeister N, Primavera F, Radburn-Smith BC, Shi X, Shipsey I, Silvers D, Sun J, Svyatkovskiy A, Wang F, Xie W, Xu L, Zablocki J, Parashar N, Stupak J, Adair A, Akgun B, Chen Z, Ecklund KM, Geurts FJM, Guilbaud M, Li W, Michlin B, Northup M, Padley BP, Redjimi R, Roberts J, Rorie J, Tu Z, Zabel J, Betchart B, Bodek A, de Barbaro P, Demina R, Eshaq Y, Ferbel T, Galanti M, Garcia-Bellido A, Goldenzweig P, Han J, Harel A, Hindrichs O, Khukhunaishvili A, Petrillo G, Verzetti M, Demortier L, Arora S, Barker A, Chou JP, Contreras-Campana C, Contreras-Campana E, Duggan D, Ferencek D, Gershtein Y, Gray R, Halkiadakis E, Hidas D, Hughes E, Kaplan S, Elayavalli RK, Lath A, Nash K, Panwalkar S, Park M, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Foerster M, Riley G, Rose K, Spanier S, York A, Bouhali O, Hernandez AC, Celik A, Dalchenko M, De Mattia M, Delgado A, Dildick S, Eusebi R, Flanagan W, Gilmore J, Kamon T, Krutelyov V, Montalvo R, Mueller R, Osipenkov I, Pakhotin Y, Patel R, Perloff A, Roe J, Rose A, Safonov A, Tatarinov A, Ulmer KA, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero PR, Faulkner J, Kunori S, Lamichhane K, Lee SW, Libeiro T, Undleeb S, Volobouev I, Appelt E, Delannoy AG, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Mao Y, Melo A, Ni H, Sheldon P, Snook B, Tuo S, Velkovska J, Xu Q, Arenton MW, Boutle S, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Lin C, Neu C, Wolfe E, Wood J, Xia F, Clarke C, Harr R, Karchin PE, Don CKK, Lamichhane P, Sturdy J, Belknap DA, Carlsmith D, Cepeda M, Christian A, Dasu S, Dodd L, Duric S, Friis E, Comber B, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ross I, Ruggles T, Sarangi T, Savin A, Sharma A, Smith N, Smith WH, Taylor D, Woods N
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Search for supersymmetry in the vector-boson fusion topology in proton-proton collisions at root s=8TeV
JOURNAL OF HIGH ENERGY PHYSICS 2015 NOV 27; ?(11):? Article 189
The first search for supersymmetry in the vector-boson fusion topology is presented. The search targets final states with at least two leptons, large missing transverse momentum, and two jets with a large separation in rapidity. The data sample corresponds to an integrated luminosity of 19.7 fb(-1) of proton-proton collisions at root s = 8TeV collected with the CMS detector at the CERN LHC. The observed dijet invariant mass spectrum is found to be consistent with the expected standard model prediction. Upper limits are set on the cross sections for chargino and neutralino production with two associated jets, assuming the supersymmetric partner of the tau lepton to be the lightest slepton and the lightest slepton to be lighter than the charginos. For a so-called compressed-mass-spectrum scenario in which the mass difference between the lightest supersymmetric particle (chi) over bar (0)(1) and the next lightest, mass-degenerate, gaugino particles (chi) over bar (0)(2) and (chi) over bar (+/-)(1) is 50 GeV, a mass lower limit of 170 GeV is set for these latter two particles.
Bournazos S, Ravetch JV
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Fc gamma receptor pathways during active and passive immunization
IMMUNOLOGICAL REVIEWS 2015 NOV; 268(1):88-103
IgG antibodies are actively produced in response to antigenic challenge or passively administered as an effective form of immunotherapy to confer immunity against foreign antigens. Their protective activity is mediated through their bifunctional nature: a variable Fab domain mediates antigen-binding specificity, whereas the constant Fc domain engages Fc receptors (FcRs) expressed on the surface of leukocytes to mediate effector functions. While traditionally considered the invariant domain of an IgG molecule, the Fc domain displays remarkable structural heterogeneity determined primarily by differences in the amino acid sequence of the various IgG subclasses and by the composition of the complex, Fc-associated biantennary N-linked glycan. These structural determinants regulate the conformational flexibility of the IgG Fc domain and affect its capacity to interact with distinct types of FcRs (type I or type II FcRs). FcR engagement activates diverse downstream immunomodulatory pathways with pleiotropic functional consequences including cytotoxicity and phagocytosis of IgG-coated targets, differentiation and activation of antigen presenting cells, modulation of T-cell activation, plasma cell survival, and regulation of antibody responses. These functions highlight the importance of FcR-mediated pathways in the modulation of adaptive immune responses and suggest a central role for IgG-FcR interactions during active and passive immunization.
Krueger JG, Suarez-Farinas M, Cueto I, Khacherian A, Matheson R, Parish LC, Leonardi C, Shortino D, Gupta A, Haddad J, Vlasuk GP, Jacobson EW
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A Randomized, Placebo-Controlled Study of SRT2104, a SIRT1 Activator, in Patients with Moderate to Severe Psoriasis
PLoS One 2015 NOV 10; 10(11):? Article e0142081
Activation of Sirtuin (silent mating type information regulation 2 homolog) 1, or SIRT1, is an unexplored therapeutic approach for treatment of inflammatory diseases. We randomized 40 patients with moderate-to-severe psoriasis (4:1) to three escalating doses of SRT2104, a selective activator of SIRT1, or placebo. Across all SRT2104 groups, 35% of patients (p<0.0001) achieved good to excellent histological improvement based on skin biopsies taken at baseline and day 84 but was not consistently in agreement with PASI. Improvement in histology was associated with modulation of IL-17 and TNF-alpha signaling pathways and keratinocyte differentiation target genes. 27 subjects (69%) across all treatment groups, including placebo, experienced at least one treatment emergent adverse event. The majority of AEs were either mild or moderate. Most common were headache (8%), dizziness (8%), upper respiratory tract infection (8%), and psoriatic arthropathy (8%). Average drug exposure increased in a dose-dependent manner for escalating doses of SRT2104 and had high intra-subject variability in exposure (AUC %CV: 51-89%). Given the interesting signals of clinical activity, impact on gene expression and the generally favorable safety profile seen in this study, further investigation of SIRT1 activators for the treatment of psoriasis is warranted.
Gnedeva K, Hudspeth AJ
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SoxC transcription factors are essential for the development of the inner ear
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2015 NOV 10; 112(45):14066-14071
Hair cells, the mechanosensory receptors of the inner ear, underlie the senses of hearing and balance. Adult mammals cannot adequately replenish lost hair cells, whose loss often results in deafness or balance disorders. To determine the molecular basis of this deficiency, we investigated the development of a murine vestibular organ, the utricle. Here we show that two members of the SoxC family of transcription factors, Sox4 and Sox11, are down-regulated after the epoch of hair cell development. Conditional ablation of SoxC genes in vivo results in stunted sensory organs of the inner ear and loss of hair cells. Enhanced expression of SoxC genes in vitro conversely restores supporting cell proliferation and the production of new hair cells in adult sensory epithelia. These results imply that SoxC genes govern hair cell production and thus advance these genes as targets for the restoration of hearing and balance.
Capitan F, Robu AC, Schiopu C, Ilie C, Chait BT, Przybylski M, Zamfir AD
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beta-Lactoglobulin detected in human milk forms noncovalent complexes with maltooligosaccharides as revealed by chip-nanoelectrospray high-resolution tandem mass spectrometry
AMINO ACIDS 2015 NOV; 47(11):2399-2407
Cow's milk protein allergy in exclusively breastfed infants, the main cause of food intolerance during the first 6 months of life, is triggered by the mother's diet. beta-Lactoglobulin (BLG) present in cow's milk is one of the most potent allergens for newborns. Since no prophylactic treatment is available, finding ligands capable of binding BLG and reducing its allergenicity is currently the focus of research. In this work, an innovative methodology encompassing microfluidics based on fully automated chip-nanoelectrospray ionization (nanoESI), coupled with high-resolution mass spectrometry (MS) on a quadrupole time-of-flight (QTOF MS) instrument was developed. This platform was employed for the assessment of the noncovalent interactions between maltohexaose (Glc(6)) and beta-lactoglobulin extracted from human milk upon deliberate intake of cow's milk. The experiments were carried out in (+) ESI mode, using ammonium acetate (pH 6.0) as the buffer and also in pure water. In both cases, the MS analysis revealed the formation of BLG-Glc(6) complex, which was characterized by top-down fragmentation in tandem MS (MS/MS) using collision-induced dissociation (CID). Our findings have a significant biomedical impact, indicating that Glc(6) binds BLG under conditions mimicking the in vivo environment and therefore might represent a ligand, able to reduce its allergenicity.
Shen WX, Plotkin JL, Francardo V, Ko WKD, Xie Z, Li Q, Fieblinger T, Wess J, Neubig RR, Lindsley CW, Conn PJ, Greengard P, Bezard E, Cenci MA, Surmeier DJ
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M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia
NEURON 2015 NOV 18; 88(4):762-773
A balanced interaction between dopaminergic and cholinergic signaling in the striatum is critical to goal-directed behavior. But how this interaction modulates corticostriatal synaptic plasticity underlying learned actions remains unclear-particularly in direct-pathway spiny projection neurons (dSPNs). Our studies show that in dSPNs, endogenous cholinergic signaling through M4 muscarinic receptors (M4Rs) promoted long-term depression of corticostriatal glutamatergic synapses, by suppressing regulator of G protein signaling type 4 (RGS4) activity, and blocked D1 dopamine receptor dependent long-term potentiation (LTP). Furthermore, in a mouse model of L-3,4-dihydroxyphenylalanine (L-DOPA)induced dyskinesia (LID) in Parkinson's disease (PD), boosting M4R signaling with positive allosteric modulator (PAM) blocked aberrant LTP in dSPNs, enabled LTP reversal, and attenuated dyskinetic behaviors. An M4R PAM also was effective in a primate LID model. Taken together, these studies identify an important signaling pathway controlling striatal synaptic plasticity and point to a novel pharmacological strategy for alleviating LID in PD patients.
Simon EP, Freije CA, Farber BA, Lalazar G, Darcy DG, Honeyman JN, Chiaroni-Clarke R, Dill BD, Molina H, Bhanot UK, La Quaglia MP, Rosenberg BR, Simon SM
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Transcriptomic characterization of fibrolamellar hepatocellular carcinoma
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2015 NOV 3; 112(44):E5916-E5925
Fibrolamellar hepatocellular carcinoma (FLHCC) tumors all carry a deletion of similar to 400 kb in chromosome 19, resulting in a fusion of the genes for the heat shock protein, DNAJ (Hsp40) homolog, subfamily B, member 1, DNAJB1, and the catalytic subunit of protein kinase A, PRKACA. The resulting chimeric transcript produces a fusion protein that retains kinase activity. No other recurrent genomic alterations have been identified. Here we characterize the molecular pathogenesis of FLHCC with transcriptome sequencing (RNA sequencing). Differential expression (tumor vs. adjacent normal tissue) was detected for more than 3,500 genes (log(2) fold change >= 1, false discovery rate <= 0.01), many of which were distinct from those found in hepatocellular carcinoma. Expression of several known oncogenes, such as ErbB2 and Aurora Kinase A, was increased in tumor samples. These and other dysregulated genes may serve as potential targets for therapeutic intervention.