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Zhou Y, Lapingo C
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Modulation of proopiomelanocortin gene expression by ethanol in mouse anterior pituitary corticotrope tumor cell AtT20
REGULATORY PEPTIDES 2014 JUN-AUG; 192(?):6-14
In humans, alcoholism is associated with a decrease in basal ACTH and cortisol levels, and blunted pituitary ACTH responses to administered corticotropin-releasing hormone (CRH) during active drinking and after long-term abstinence. Preclinical studies indicate that a persistent decrease in pituitary activation after chronic exposure to ethanol is due to a direct effect of ethanol on the corticotrope of the anterior pituitary. The present studies were undertaken to determine if ethanol has effects on proopiomelanocortin (POMC) gene transcription activity in mouse anterior pituitary corticotrope tumor cell AtT20. We measured the levels of the POMC primary nuclear RNA transcript (PT), processing intermediate, and mature mRNA in the nucleus and the levels of the POMC mRNA in the cytoplasm after treatment of AtT20 cells with 5-15 mM concentrations of ethanol. After 15 mM ethanol for 60 to 120 min, the POMC PT levels were significantly decreased. This decreased POMC gene transcription activity was coupled with a significant reduction of the POMC cytoplasmic mRNA levels. After ethanol for 4 h, however, both the decreases were no longer observed. After 8 h, a decrease in the ACTH secretion in the medium was found. We further investigated if CRH or glutamate modulates the effects of ethanol on the POMC gene transcription activity. CRH at 10 nM after 60 min increased the POMC PT levels, and 15 mM ethanol attenuated the effect of CRH on the nuclear transcription activity. Glutamate receptor proteins, including NMDA receptor subtype NR1 (but not NR2A or NR2B) and GluR2, were identified by Western immunoblot analysis in AtT20 cells, with similar sizes to those in mouse hypothalamus. The inhibitory effect of 60 min ethanol at 5 to 15 mM on the POMC PT levels was attenuated by 50 mu M L-glutamate. Together, our data showed that: (1) ethanol treatment in intoxicate doses significantly inhibited POMC gene transcription activity in a dose- and time-dependent manner in AtT20 cells, and (2) the POMC gene transcription activity in response to CRH or glutamate was altered by ethanol. Our results suggest that ethanol has an inhibitory effect on the POMC gene transcription activity in the anterior pituitary corticotrope, which may contribute to the persistent decrease in pituitary activation after chronic ethanol exposure. (C) 2014 Elsevier B.V. All rights reserved.
Bargmann CI, Newsome WT
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The Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative and Neurology
JAMA NEUROLOGY 2014 JUN; 71(6):675-676
Kang HS, Brady SF
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Arixanthomycins A-C: Phylogeny-Guided Discovery of Biologically Active eDNA-Derived Pentangular Polyphenols
ACS CHEMICAL BIOLOGY 2014 JUN; 9(6):1267-1272
Soil microbiomes are a rich source of uncharacterized natural product biosynthetic gene clusters. Here we use short conserved biosynthetic gene sequences (natural product sequence tags) amplified from soil microbiomes as phylogenetic markers to correlate genotype to chemotype and target the discovery of novel bioactive pentangular polyphenols from the environment. The heterologous expression of an environmental DNA-derived gene cluster (the ARX cluster), whose ketosynthase beta (KS beta) sequence tag was phylogenetically distinct from any known KS beta sequence, led to the discovery of the arixanthomycins. Arixanthomycin A (1) exhibits potent antiproliferative activity against human cancer cell lines.
Schaefer U
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Pharmacological Inhibition of Bromodomain-Containing Proteins in Inflammation
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY 2014 JUN; 6(6):? Article a018671
Inflammation is associated with the activation of genes that contribute to immune defense and tissue repair. The bromodomain-containing proteins of the BET family, which recognize histone lysine acetylation, play a key role in the transcriptional control of inflammatory genes. Inhibition of BET proteins by the small-molecule inhibitor I-BET affects the expression of a particular subset of inflammatory genes-namely, ones that follow an "analog-like," but not "digital-like" activation pattern. This ability of I-BET to target genes based on the dynamic pattern of their activation may facilitate the further development of anti-inflammatory treatment protocols that are tuned to the individual or to disease-specific patterns of gene expression.
Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, Ero J, Fabjan C, Friedl M, Fruhwirth R, Ghete VM, Hormann N, Hrubec J, Jeitler M, Kiesenhofer W, Knunz V, Krammer M, Kratschmer I, Liko D, Mikulec I, Rabady D, Rahbaran B, Rohringer C, Rohringer H, Schofbeck R, Strauss J, Taurok A, Treberer-Treberspurg W, Waltenberger W, Wulz CE, Mossolov V, Shumeiko N, Gonzalez JS, Alderweireldt S, Bansal M, Bansal S, Cornelis T, Wolf EA, Janssen X, Knutsson A, Luyckx S, Mucibello L, Ochesanu S, Roland B, Rougny R, Staykova Z, Van Haevermaet H, Van Mechelen P, Van Remortel N, Van Spilbeeck A, Blekman F, Blyweert S, D'Hondt J, Kalogeropoulos A, Keaveney J, Maes M, Olbrechts A, Tavernier S, Van Doninck W, Van Mulders P, Van Onsem GP, Villella I, Caillol C, Clerbaux B, De Lentdecker G, Favart L, Gay APR, Hreus T, Leonard A, Marage PE, Mohammadi A, Pernie L, Reis T, Seva T, Thomas L, Vander Velde C, Vanlaer P, Wang J, Adler V, Beernaert K, Benucci L, Cimmino A, Costantini S, Dildick S, Garcia G, Klein B, Lellouch J, Marinov A, Mccartin J, Rios AAO, Ryckbosch D, Sigamani M, Strobbe N, Thyssen F, Tytgat M, Walsh S, Yazgan E, Zaganidis N, Basegmez S, Beluffi C, Bruno G, Castello R, Caudron A, Ceard L, Da Silveira GG, Delaere C, du Pree T, Favart D, Forthomme L, Giammanco A, Hollar J, Jez P, Lemaitre V, Liao J, Militaru O, Nuttens C, Pagano D, Pin A, Piotrzkowski K, Popov A, Selvaggi M, Marono MV, Garcia JMV, Beliy N, Caebergs T, Daubie E, Hammad GH, Alves GA, Martins MC, Martins T, Pol ME, Souza MHG, Alda WL, Carvalho W, Chinellato J, Custodio A, Da Costa EM, Damiao DD, Martins CD, De Souza SF, Malbouisson H, Malek M, Figueiredo DM, Mundim L, Nogima H, Da Silva WLP, Santoro A, Sznajder A, Manganote EJT, Pereira AV, Bernardes CA, Dias FA, Tomei TRFP, Gregores EM, Lagana C, Mercadante PG, Novaes SF, Padula SS, Genchev V, Iaydjiev P, Piperov S, Rodozov M, Sultanov G, Vutova M, Dimitrov A, Hadjiiska R, Kozhuharov V, Litov L, Pavlov B, Petkov P, Bian JG, Chen GM, Chen HS, Jiang CH, Liang D, Liang S, Meng X, Tao J, Wang X, Wang Z, Xiao H, Asawatangtrakuldee C, Ban Y, Guo Y, Li Q, Li W, Liu S, Mao Y, Qian SJ, Wang D, Zhang L, Zou W, Avila C, Montoya AC, Sierra LFC, Gomez JP, Moreno BG, Sanabria JC, Godinovic N, Lelas D, Plestina R, Polic D, Puljak I, Antunovic Z, Kovac M, Brigljevic V, Kadija K, Luetic J, Mekterovic D, Morovic S, Tikvica L, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Finger M, Finger M, Abdelalim AA, Assran Y, Elgammal S, Kamel AE, Mahmoud MA, Radi A, Kadastik M, Muntel M, Murumaa M, Raidal M, Rebane L, Tiko A, Eerola P, Fedi G, Voutilainen M, Harkonen J, Karimaki V, Kinnunen R, Kortelainen MJ, Lampen T, Lassila-Perini K, Lehti S, Linden T, Luukka P, Maenpaa T, Peltola T, Tuominen E, Tuominiemi J, Tuovinen E, Wendland L, Tuuva T, Besancon M, Couderc F, Dejardin M, Denegri D, Fabbro B, Faure JL, Ferri F, Ganjour S, Givernaud A, Gras P, de Monchenault GH, Jarry P, Locci E, Malcles J, Millischer L, Nayak A, Rander J, Rosowsky A, Titov M, Baffioni S, Beaudette F, Benhabib L, Bluj M, Busson P, Charlot C, Daci N, Dahms T, Dalchenko M, Dobrzynski L, Florent A, de Cassagnac RG, Hague-Nauer M, Mine P, Mironov C, Naranjo IN, Nguyen M, Ochando C, Paganini P, Sabes D, Salerno R, Sirois Y, Veelken C, Zabi A, Agram JL, Andrea J, Bloch D, Brom JM, Chabert EC, Collard C, Conte E, Drouhin F, Fontaine JC, Gele D, Goerlach U, Goetzmann C, Juillot P, Le Bihan AC, Van Hove P, Gadrat S, Beauceron S, Beaupere N, Boudoul G, Brochet S, Chasserat J, Chierici R, Contardo D, Depasse P, El Mamouni H, Fan J, Fay J, Gascon S, Gouzevitch M, Ille B, Kurca T, Lethuillier M, Mirabito L, Perries S, Sgandurra L, Sordini V, Vander Donckt M, Verdier P, Viret S, Tsamalaidze Z, Autermann C, Beranek S, Bontenackels M, Calpas B, Edelhoff M, Feld L, Heracleous N, Hindrichs O, Klein K, Ostapchuk A, Perieanu A, Raupach F, Sammet J, Schael S, Sprenger D, Weber H, Wittmer B, Zhukov V, Ata M, Caudron J, Dietz-Laursonn E, Duchardt D, Erdmann M, Fischer R, Guth A, Hebbeker T, Heidemann C, Hoepfner K, Klingebiel D, Knutzen S, Kreuzer P, Merschmeyer M, Meyer A, Olschewski M, Padeken K, Papacz P, Pieta H, Reithler H, Schmitz SA, Sonnenschein L, Steggemann J, Teyssier D, Thuer S, Weber M, Cherepanov V, Erdogan Y, Flugge G, Geenen H, Geisler M, Ahmad WH, Hoehle F, Kargoll B, Kress T, Kuessel Y, Lingemann J, Nowack A, Nugent IM, Perchalla L, Pooth O, Stahl A, Asin I, Bartosik N, Behr J, Behrenhoff W, Behrens U, Bell AJ, Bergholz M, Bethani A, Borras K, Burgmeier A, Cakir A, Calligaris L, Campbell A, Choudhury S, Costanza F, Pardos CD, Dooling S, Dorland T, Eckerlin G, Eckstein D, Flucke G, Geiser A, Glushkov I, Grebenyuk A, Gunnellini P, Habib S, Hauk J, Hellwig G, Horton D, Jung H, Kasemann M, Katsas P, Kleinwort C, Kluge H, Amer MK, Krucker D, Kuznetsova E, Lange W, Leonard J, Lipka K, Lohmann W, Lutz B, Mankel R, Marfin I, Melzer-Pellmann IA, Meyer AB, Mnich J, Mussgiller A, Naumann-Emme S, Novgorodova O, Nowak F, Olzem J, Perrey H, Petrukhin A, Pitzl D, Placakyte R, Raspereza A, Cipriano PMR, Riedl C, Ron E, Sahin MO, Salfeld-Nebgen J, Schmidt R, Schoerner-Sadenius T, Sen N, Stein M, Walsh R, Wissing C, Martin MA, Blobel V, Enderle H, Erfle J, Garutti E, Gebbert U, Gorner M, Gosselink M, Haller J, Heine K, Hoing RS, Kaussen G, Kirschenmann H, Klanner R, Kogler R, Lange J, Marchesini I, Peiffer T, Pietsch N, Rathjens D, Sander C, Schettler H, Schleper P, Schlieckau E, Schmidt A, Schroder M, Schum T, Seidel M, Sibille J, Sola V, Stadie H, Steinbruck G, Thomsen J, Troendle D, Usai E, Vanelderen L, Barth C, Baus C, Berger J, Boser C, Butz E, Chwalek T, De Boer W, Descroix A, Dierlamm A, Feindt M, Guthoff M, Hartmann F, Hauth T, Held H, Hoffmann KH, Husemann U, Katkov I, Komaragiri JR, Kornmayer A, Pardo PL, Martschei D, Muller T, Niegel M, Nurnberg A, Oberst O, Ott J, Quast G, Rabbertz K, Ratnikov F, Rocker S, Schilling FP, Schott G, Simonis HJ, Stober FM, Ulrich R, Wagner-Kuhr J, Wayand S, Weiler T, Zeise M, Anagnostou G, Daskalakis G, Geralis T, Kesisoglou S, Kyriakis A, Loukas D, Markou A, Markou C, Ntomari E, Topsis-giotis I, Gouskos L, 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, Molnar J, Palinkas J, Szillasi Z, Karancsi J, Raics P, Trocsanyi ZL, Ujvari B, Swain SK, Beri SB, Bhatnagar V, Dhingra N, Gupta R, Kaur M, Mehta MZ, Mittal M, Nishu N, Sharma A, Singh JB, Kumar A, Kumar A, Ahuja S, Bhardwaj A, Choudhary BC, Malhotra S, Naimuddin M, Ranjan K, Saxena P, Sharma V, Shivpuri RK, 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, Singh AP, Abdulsalam A, Dutta D, Kailas S, Kumar V, Mohanty AK, Pant LM, Shukla P, Topkar A, Aziz T, Chatterjee RM, 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, Banerjee S, Dugad S, Arfaei H, Bakhshiansohi H, Etesami SM, Fahim A, Jafari A, Khakzad M, Najafabadi MM, Mehdiabadi SP, Safarzadeh B, Zeinali 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, Marangelli B, My S, Nuzzo S, Pacifico N, Pompili A, Pugliese G, 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, Meneghelli M, Montanari A, Navarria FL, Odorici F, Perrotta A, Primavera F, Rossi AM, Rovelli T, Siroli GP, Tosi N, Travaglini R, Albergo S, Chiorboli M, Costa S, Giordano F, Potenza R, Tricomi A, Tuve C, Barbagli G, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Frosali S, Gallo E, Gonzi S, Gori V, Lenzi P, Meschini M, Paoletti S, Sguazzoni G, Tropiano A, Benussi L, Bianco S, Fabbri F, Piccolo D, Fabbricatore P, Ferretti R, Ferro F, Lo Vetere M, Musenich R, Robutti E, Tosi S, Benaglia A, Dinardo ME, Fiorendi S, Gennai S, Ghezzi A, Govoni P, Lucchini MT, Malvezzi S, Manzoni RA, Martelli A, Menasce D, Moroni L, Paganoni M, Pedrini D, Ragazzi S, Redaelli N, de Fatis TT, Buontempo S, Cavallo N, De Cosa A, Fabozzi F, Iorio AOM, Lista L, Meola S, Merola M, Paolucci P, Azzi P, Bacchetta N, Bellato M, Biasotto M, Bisello D, Branca A, Carlin R, Checchia P, Dorigo T, Galanti M, Gasparini F, Gasparini U, Giubilato P, Gozzelino A, Kanishchev K, Lacaprara S, Lazzizzera I, Margoni M, Meneguzzo AT, Pozzobon N, Ronchese P, Sgaravatto M, Simonetto F, Torassa E, Tosi M, Triossi A, Ventura S, Zotto P, Zucchetta A, Zumerle G, Gabusi M, Ratti SP, Riccardi C, Vitulo P, Biasini M, Bilei GM, Fano L, Lariccia P, Mantovani G, Menichelli M, Nappi A, Romeo F, Saha A, Santocchia A, Spiezia A, Androsov K, Azzurri P, Bagliesi G, Bernardini J, Boccali T, Broccolo G, Castaldi R, Ciocci MA, D'Agnolo RT, Dell'Orso R, Fiori F, Foa L, Giassi A, Grippo MT, Kraan A, 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 G, Vernieri C, Barone L, Cavallari F, Del Re D, Diemoz M, Grassi M, Longo E, Margaroli F, Meridiani P, Micheli F, Nourbakhsh S, Organtini G, Paramatti R, Rahatlou S, Rovelli C, Soffi L, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Bellan R, Biino C, Cartiglia N, Casasso S, Costa M, Degano A, Demaria N, Mariotti C, Maselli S, Migliore E, Monaco V, Musich M, Obertino MM, Pastrone N, Pelliccioni M, 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, Penzo A, Schizzi A, Zanetti A, Chang S, Kim TY, Nam SK, Kim DH, Kim GN, Kim JE, Kong DJ, Lee S, Oh YD, Park H, Son DC, Kim JY, Kim ZJ, Song S, Choi S, Gyun D, Hong B, Jo M, Kim H, Kim TJ, Lee KS, Park SK, Roh Y, Choi M, Kim JH, Park C, Park IC, Park S, Ryu G, Choi Y, Choi YK, Goh J, Kim MS, Kwon E, Lee B, Lee J, Lee S, Seo H, Yu I, Grigelionis I, Juodagalvis A, Castilla-Valdez H, De la Cruz-Burelo E, Heredia-de La Cruz I, Lopez-Fernandez R, Martinez-Ortega J, Sanchez-Hernandez A, Villasenor-Cendejas LM, Moreno SC, Valencia FV, Ibarguen HAS, Linares EC, Pineda AM, Reyes-Santos MA, Krofcheck D, Butler PH, Doesburg R, Reucroft S, Silverwood H, Ahmad M, Asghar MI, Butt J, Hoorani HR, Khan WA, Khurshid T, Qazi S, Shoaib M, Bialkowska H, Boimska B, Frueboes T, Gorski M, Kazana M, Nawrocki K, Romanowska-Rybinska K, Szleper M, Wrochna G, Zalewski P, Brona G, Bunkowski K, Cwiok M, Dominik W, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Wolszczak W, Almeida N, Bargassa P, Silva CBDE, Faccioli P, Parracho PGF, Gallinaro M, Nguyen F, Antunes JR, Seixas J, Varela J, Vischia P, Afanasiev S, Bunin P, Gavrilenko M, Golutvin I, Gorbunov I, Kamenev A, Karjavin V, Konoplyanikov V, Lanev A, Malakhov A, Matveev V, Moisenz P, Palichik V, Perelygin V, Shmatov S, Skatchkov N, Smirnov V, Zarubin A, Evstyukhin S, 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, Erofeeva M, 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, Bunichev V, Dubinin M, Dudko L, Ershov A, Gribushin A, Klyukhin V, Kodolova O, Lokhtin I, Markina A, 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, Djordjevic M, Ekmedzic M, Krpic D, Milosevic J, Aguilar-Benitez M, Maestre JA, Battilana C, Calvo E, Cerrada M, Llatas MC, Colino N, De la Cruz B, Peris AD, Vazquez DD, Bedoya CF, Ramos JPF, Ferrando A, Flix J, Fouz MC, Garcia-Abia P, Lopez OG, Lopez SG, Hernandez JM, Josa MI, Merino G, De Martino EN, Pelayo JP, Olmeda AQ, Redondo I, Romero L, Santaolalla J, Soares MS, Willmott C, Albajar C, de Troconiz JF, Brun H, Cuevas J, Menendez JF, Folgueras S, Caballero IG, Iglesias LL, Gomez JP, Cifuentes JAB, Cabrillo IJ, Calderon A, Chuang SH, Campderros JD, Fernandez M, Gomez G, Sanchez JG, Graziano A, Jorda C, Virto AL, Marco J, Marco R, Rivero CM, Matorras F, Sanchez FJM, 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, Bendavid J, Benitez JF, Bernet C, Bianchi G, Bloch P, Bocci A, Bonato A, Bondu O, Botta C, Breuker H, Camporesi T, Cerminara G, Christiansen T, Perez JAC, Colafranceschi S, D'Alfonso M, d'Enterria D, Dabrowski A, David A, De Guio F, De Roeck A, De Visscher S, Di Guida S, Dobson M, Dupont-Sagorin N, Elliott-Peisert A, Eugster J, Funk W, Georgiou G, Giffels M, Gigi D, Gill K, Giordano D, Girone M, Giunta M, Glege F, Garrido RGR, Gowdy S, Guida R, Hammer J, Hansen M, Harris P, Hartl C, Hinzmann A, Innocente V, Janot P, Karavakis E, Kousouris K, Krajczar K, Lecoq P, Lee YJ, Lourenco C, Magini N, Malgeri L, Mannelli M, Masetti L, Meijers F, Mersi S, Meschi E, Moser R, Mulders M, Musella P, Nesvold E, Orsini L, Cortezon EP, Perez E, Perrozzi L, Petrilli A, Pfeiffer A, Pierini M, Pimia M, Piparo D, Plagge M, Quertenmont L, Racz A, Reece W, Rolandi G, Rovere M, Sakulin H, Santanastasio F, Schafer C, Schwick C, Segoni I, Sekmen S, Sharma A, Siegrist P, Silva P, Simon M, Sphicas P, Spiga D, Stoye M, 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Incandela J, Justus C, Kovalskyi D, Krutelyov V, Lowette S, Villalba RM, Mccoll N, Pavlunin V, Richman J, Rossin R, Stuart D, To W, West C, Apresyan A, Bornheim A, Bunn J, Chen Y, Di Marco E, Duarte J, Kcira D, Ma Y, Mott A, Newman HB, Pena C, Rogan C, Spiropulu M, Timciuc V, Veverka J, Wilkinson R, Xie S, Zhu RY, Azzolini V, Calamba A, Carroll R, Ferguson T, Iiyama Y, Jang DW, Liu YF, Paulini M, Russ J, Vogel H, Vorobiev I, Cumalat JP, Drell BR, Ford WT, Gaz A, Lopez EL, Nauenberg U, Smith JG, Stenson K, Ulmer KA, Wagner SR, Alexander J, Chatterjee A, Eggert N, Gibbons LK, Hopkins W, Khukhunaishvili A, Kreis B, Mirman N, Kaufman GN, Patterson JR, Ryd A, Salvati E, 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, Chetluru V, Cheung HWK, Chlebana F, Cihangir S, Elvira VD, Fisk I, Freeman J, Gao Y, Gottschalk E, Gray L, Green D, Gutsche O, Hare D, Harris RM, Hirschauer J, Hooberman B, Jindariani S, Johnson M, Joshi U, Kaadze K, Klima B, Kunori S, Kwan S, Linacre J, Lincoln D, Lipton R, Lykken J, Maeshima K, Marraffino JM, Outschoorn VIM, Maruyama S, Mason D, McBride P, Mishra K, Mrenna S, Musienko Y, Newman-Holmes C, O'Dell V, Prokofyev O, Ratnikova N, Sexton-Kennedy E, Sharma S, Spalding WJ, Spiegel L, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vidal R, Whitmore J, Wu W, Yang F, Yun JC, Acosta D, Avery P, Bourilkov D, Chen M, Cheng T, Das S, De Gruttola M, Di Giovanni GP, Dobur D, Drozdetskiy A, Field RD, Fisher M, Fu Y, Furic IK, Hugon J, Kim B, Konigsberg J, Korytov A, Kropivnitskaya A, Kypreos T, Low JF, Matchev K, Milenovic P, Mitselmakher G, Muniz L, Remington R, Rinkevicius A, Skhirtladze N, Snowball M, Yelton J, Zakaria M, Gaultney V, Hewamanage S, Linn S, Markowitz P, Martinez G, Rodriguez JL, Adams T, Askew A, Bochenek J, Chen J, Diamond B, Haas J, Hagopian S, Hagopian V, Johnson KF, Prosper H, Veeraraghavan V, Weinberg M, Baarmand MM, Dorney B, Hohlmann M, Kalakhety H, Yumiceva F, Adams MR, Apanasevich L, Bazterra VE, Betts RR, Bucinskaite I, Callner J, Cavanaugh R, Evdokimov O, Gauthier L, Gerber CE, Hofman DJ, Khalatyan S, Kurt P, Lacroix F, Moon DH, O'Brien C, Silkworth C, Strom D, Turner P, Varelas N, Akgun U, Albayrak EA, Bilki B, Clarida W, Dilsiz K, Duru F, Griffiths S, Merlo JP, Mermerkaya H, Mestvirishvili A, Moeller A, Nachtman J, Newsom CR, Ogul H, Onel Y, Ozok F, Sen S, Tan P, Tiras E, Wetzel J, Yetkin T, Yi K, Barnett BA, Blumenfeld B, Bolognesi S, Giurgiu G, Gritsan AV, Hu G, Maksimovic P, Martin C, Swartz M, Whitbeck A, Baringer P, Bean A, Benelli G, Kenny RP, Murray M, Noonan D, Sanders S, Stringer R, Wood JS, Barfuss AF, Chakaberia I, Ivanov A, Khalil S, Makouski M, Maravin Y, Saini LK, Shrestha S, Svintradze I, Gronberg J, Lange D, Rebassoo F, Wright D, Baden A, Calvert B, Eno SC, Gomez JA, Hadley NJ, Kellogg RG, Kolberg T, Lu Y, Marionneau M, Mignerey AC, Pedro K, Peterman A, Skuja A, Temple J, Tonjes MB, Tonwar SC, Apyan A, Bauer G, Busza W, Cali IA, Chan M, Di Matteo L, Dutta V, Ceballos GG, Goncharov M, Gulhan D, Kim Y, Klute M, Lai YS, Levin A, Luckey PD, Ma T, Nahn S, Paus C, Ralph D, Roland C, Roland G, Stephans GSF, Stockli F, Sumorok K, Velicanu D, Wolf R, Wyslouch B, Yang M, Yilmaz Y, Yoon AS, Zanetti M, Zhukova V, Dahmes B, De Benedetti A, Franzoni G, Gude A, Haupt J, Kao SC, Klapoetke K, Kubota Y, Mans J, Pastika N, Rusack R, Sasseville M, Singovsky A, Tambe N, Turkewitz J, Acosta JG, Cremaldi LM, Kroeger R, Oliveros S, Perera L, Rahmat R, Sanders DA, Summers D, Avdeeva E, Bloom K, Bose S, Claes DR, Dominguez A, Eads M, Suarez RG, Keller J, Kravchenko I, Lazo-Flores J, Malik S, Meier F, Snow GR, Dolen J, Godshalk A, Iashvili I, Jain S, Kharchilava A, Kumar A, Rappoccio S, Wan Z, Alverson G, Barberis E, Baumgartel D, Chasco M, Haley J, Massironi A, Nash D, Orimoto T, Trocino D, Wood D, Zhang J, Anastassov A, Hahn KA, Kubik A, 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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, Miner DC, Petrillo G, Vishnevskiy D, Zielinski M, Bhatti A, Ciesielski R, Demortier L, Goulianos K, Lungu G, Malik S, 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, Lath A, Panwalkar S, Park M, Patel R, Rekovic V, Robles J, Salur S, Schnetzer S, Seitz C, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Cerizza G, Hollingsworth M, Rose K, Spanier S, Yang ZC, York A, Bouhali O, Eusebi R, Flanagan W, Gilmore J, Kamon T, Khotilovich V, Montalvo R, Osipenkov I, Pakhotin Y, Perloff A, Roe J, Safonov A, Sakuma T, Suarez I, Tatarinov A, Toback D, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero PR, Kovitanggoon K, 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, Lin C, Neu C, Wood J, Gollapinni S, Harr R, Karchin PE, Don CKK, Lamichhane P, Sakharov A, Belknap DA, Borrello L, Carlsmith D, Cepeda M, Dasu S, Duric S, Friis E, Grothe M, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Klukas J, Lanaro A, Loveless R, Mohapatra A, Mozer MU, Ojalvo I, Perry T, Pierro GA, Polese G, Ross I, Sarangi T, Savin A, Smith WH, Swanson J
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Search for pair production of excited top quarks in the lepton plus jets final state
JOURNAL OF HIGH ENERGY PHYSICS 2014 JUN 19; ?(6):? Article 125
A search is performed for pair-produced spin-3/2 excited top quarks , each decaying to a top quark and a gluon. The search uses data collected with the CMS detector from pp collisions at a center-of-mass energy of = 8 TeV, selecting events that have a single isolated muon or electron, an imbalance in transverse momentum, and at least six jets, of which one must be compatible with originating from the fragmentation of a b quark. The data, corresponding to an integrated luminosity of 19.5 fb(-1), show no significant excess over standard model predictions, and provide a lower limit of 803 GeV at 95% confidence on the mass of the spin-3/2 t(*) quark in an extension of the Randall-Sundrum model, assuming a 100% branching fraction of its decay into a top quark and a gluon. This is the first search for a spin-3/2 excited top quark performed at the LHC.
Zhang QR, Long Q, Ott J
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AprioriGWAS, a New Pattern Mining Strategy for Detecting Genetic Variants Associated with Disease through Interaction Effects
PLOS COMPUTATIONAL BIOLOGY 2014 JUN; 10(6):? Article e1003627
Identifying gene-gene interaction is a hot topic in genome wide association studies. Two fundamental challenges are: (1) how to smartly identify combinations of variants that may be associated with the trait from astronomical number of all possible combinations; and (2) how to test epistatic interaction when all potential combinations are available. We developed AprioriGWAS, which brings two innovations. (1) Based on Apriori, a successful method in field of Frequent Itemset Mining (FIM) in which a pattern growth strategy is leveraged to effectively and accurately reduce search space, AprioriGWAS can efficiently identify genetically associated genotype patterns. (2) To test the hypotheses of epistasis, we adopt a new conditional permutation procedure to obtain reliable statistical inference of Pearson's chi-square test for the 2 x f contingency table generated by associated variants. By applying AprioriGWAS to age-related macular degeneration (AMD) data, we found that: (1) angiopoietin 1 (ANGPT1) and four retinal genes interact with Complement Factor H (CFH). (2) GO term "glycosaminoglycan biosynthetic process" was enriched in AMD interacting genes. The epistatic interactions newly found by AprioriGWAS on AMD data are likely true interactions, since genes interacting with CFH are retinal genes, and GO term enrichment also verified that interaction between glycosaminoglycans (GAGs) and CFH plays an important role in disease pathology of AMD. By applying AprioriGWAS on Bipolar disorder in WTCCC data, we found variants without marginal effect show significant interactions. For example, multiple-SNP genotype patterns inside gene GABRB2 and GRIA1 (AMPA subunit 1 receptor gene). AMPARs are found in many parts of the brain and are the most commonly found receptor in the nervous system. The GABRB2 mediates the fastest inhibitory synaptic transmission in the central nervous system. GRIA1 and GABRB2 are relevant to mental disorders supported by multiple evidences.
Kao SH, Wang WL, Chen CY, Chang YL, Wu YY, Wang YT, Wang SP, Nesvizhskii AI, Chen YJ, Hong TM, Yang PC
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GSK3 beta controls epithelial-mesenchymal transition and tumor metastasis by CHIP-mediated degradation of Slug
ONCOGENE 2014 JUN 12; 33(24):3172-3182
Glycogen synthase kinase 3 beta (GSK3 beta) is highly inactivated in epithelial cancers and is known to inhibit tumor migration and invasion. The zinc-finger-containing transcriptional repressor, Slug, represses E-cadherin transcription and enhances epithelial mesenchymal transition (EMT). In this study, we find that the GSK3 beta-pSer9 level is associated with the expression of Slug in non-small cell lung cancer. GSK3 beta-mediated phosphorylation of Slug facilitates Slug protein turnover. Proteomic analysis reveals that the carboxyl terminus of Hsc70-interacting protein (CHIP) interacts with wild-type Slug (wtSlug). Knockdown of CHIP stabilizes the wtSlug protein and reduces Slug ubiquitylation and degradation. In contrast, nonphosphorylatable Slug-4SA is not degraded by CHIP. The accumulation of nondegradable Slug may further lead to the repression of E-cadherin expression and promote cancer cell migration, invasion and metastasis. Our findings provide evidence of a de novo GSK3 beta-CHIP-Slug pathway that may be involved in the progression of metastasis in lung cancer.
Dinces SM, Romeo RD, McEwen BS, Tang AC
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Enhancing offspring hypothalamic-pituitary-adrenal (HPA) regulation via systematic novelty exposure: the influence of maternal HPA function
FRONTIERS IN BEHAVIORAL NEUROSCIENCE 2014 JUN 5; 8(?):? Article 204
In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother's ability to mount a rapid corticosterone (COAT) response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring hypothalamic-pituitary-adrenal (HPA) regulation. Using a 2 x 2 within-litter design, one half of each litter were exposed to a relatively novel non home environment for 3-min (Neo_Novel) daily during infancy (PND 1-21) and the other half of the litter remained in the home cage (Neo_Home); we further exposed half of these two groups to early adulthood (PND 54-63) novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting COAT (CORTB) and the ability to mount a large rapid CORT response (CORTE) to the onset of an acute stressor. Assessment of adult offspring's ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring's ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the context of maternal HPA regulation.
Khattri S, Shemer A, Rozenblit M, Dhingra N, Czarnowicki T, Finney R, Gilleaudeau P, Sullivan-Whalen M, Zheng XZ, Xu H, Cardinale I, Strong CD, Gonzalez J, Suarez-Farinas M, Krueger JG, Guttman-Yassky E
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Cyclosporine in patients with atopic dermatitis modulates activated inflammatory pathways and reverses epidermal pathology
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 2014 JUN; 133(6):1626-1634
Background: Atopic dermatitis (AD) is the most common inflammatory disease. Evolving disease models link changes in epidermal growth and differentiation to T(H)2/T(H)22 cytokine activation. However, these models have not been tested by in vivo suppression of T-cell cytokines. Cyclosporine (CsA) is an immunosuppressant that is highly effective for severe disease, but its mechanism in AD skin lesions has not been studied. Objective: We sought to establish the ability of a systemic immunosuppressant to modulate immune and epidermal alterations that form the pathogenic disease phenotype and to correlate changes with clinical improvement. Methods: CsA's effects on AD skin pathology were evaluated by using gene expression and immunohistochemistry studies in baseline, week 2, and week 12 lesional and nonlesional biopsy specimens from 19 patients treated with 5 mg/kg/d CsA for 12 weeks. Results: After 2 and 12 weeks of treatment, we observed significant reductions of 51% and 72%, respectively, in SCORAD scores. Clinical improvements were associated with significant gene expression changes in lesional but also nonlesional skin, particularly reductions in levels of T(H)2-, T(H)22-, and some T(H)17-related molecules (ie, IL-13, IL-22, CCL17, S100As, and elafin/peptidase inhibitor 3), and modulation of epidermal hyperplasia and differentiation measures. Conclusions: This is the first study that establishes a relationship between cytokine activation and molecular epidermal alterations, as well as correlations between disease biomarkers in the skin and clinical improvement. The reversal of the molecular phenotype with CsA and the associated biomarkers can serve as a reference for the successful modulation of tissue inflammation with specific immune antagonists in future studies, contributing to the understanding of the specific cytokines involved in epidermal pathology.