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Found 37769 matches. Displaying 7181-7190
Toth M, Gresack JE, Hauger RL, Halberstadt AL, Risbrough VB
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The role of PKC signaling in CRF-induced modulation of startle
PSYCHOPHARMACOLOGY 2013 OCT; 229(4):579-589
Hypersignaling of corticotropin releasing factor (CRF) has been implicated in stress disorders; however, many of its downstream mechanisms of action remain unclear. In vitro, CRF1 receptor activation initiates multiple cell signaling cascades, including protein kinase A (PKA), protein kinase C (PKC), and mitogen-activated protein kinase kinase MEK1/2 signaling. It is unclear, however, which of these signaling cascades mediate CRF-induced behaviors during stress. We examined the role of PKA, PKC, and MEK1/2 signaling pathways in CRF-induced anxiety as measured by startle hyperreactivity. Mice treated with intracerbroventricular (ICV) ovine CRF (oCRF) were pretreated with the PKA inhibitor Rp-cAMPS, PKC inhibitor bisindolylmaleimide (BIM), or MEK1/2 inhibitor PD98059 (ICV) and assessed for acoustic startle reactivity. The PKC inhibitor BIM significantly attenuated CRF-induced increases in startle. BIM was also able to block startle increases induced by oCRF when both compounds were infused directly into the bed nucleus of stria terminalis (BNST). PKA and MEK1/2 inhibition had no significant effects on CRF-induced changes in startle at the dose ranges tested. CRF-induced disruption of prepulse inhibition was not significantly reversed by any of the three pretreatments at the dose ranges tested. PKC signaling is required for CRF-induced increases in startle, and this effect is mediated at least in part at the BNST. These findings suggest that PKC signaling cascades (1) may be important for the acute effects of CRF to induce startle hyperreactivity and (2) support further research of the role of PKC signaling in startle abnormalities relevant to disorders such as posttraumatic stress disorder.
Gagnidze K, Weil ZM, Faustino LC, Schaafsma SM, Pfaff DW
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Early Histone Modifications in the Ventromedial Hypothalamus and Preoptic Area Following Oestradiol Administration
JOURNAL OF NEUROENDOCRINOLOGY 2013 OCT; 25(10):939-955
Expression of the primary female sex behaviour, lordosis, in laboratory animals depends on oestrogen-induced expression of progesterone receptor (PgR) within a defined cell group in the ventrolateral portion of the ventromedial nucleus of the hypothalamus (VMH). The minimal latency from oestradiol administration to lordosis is 18 h. During that time, ligand-bound oestrogen receptors (ER), members of a nuclear receptor superfamily, recruit transcriptional coregulators, which induce covalent modifications of histone proteins, thus leading to transcriptional activation or repression of target genes. The present study aimed to investigate the early molecular epigenetic events underlying oestrogen-regulated transcriptional activation of the Pgr gene in the VMH of female mice. Oestradiol (E-2) administration induced rapid and transient global histone modifications in the VMH of ovariectomised female mice. Histone H3 N-terminus phosphorylation (H3S10phK14Ac), acetylation (H3Ac) and methylation (H3K4me3) exhibited distinct temporal patterns facilitative to the induction of transcription. A transcriptional repressive (H3K9me3) modification showed a different temporal pattern. Collectively, this should create a permissive environment for the transcriptional activity necessary for lordosis, within 3-6 h after E-2 treatment. In the VMH, changes in the H3Ac and H3K4me3 levels of histone H3 were also detected at the promoter region of the Pgr gene within the same time window, although they were delayed in the preoptic area. Moreover, examination of histone modifications associated with the promoter of another ER-target gene, oxytocin receptor (Oxtr), revealed gene- and brain-region specific effects of E-2 treatment. In the VMH of female mice, E-2 treatment resulted in the recruitment of ER alpha to the oestrogen-response-elements-containing putative enhancer site of Pgr gene, approximately 200 kb upstream of the transcription start site, although it failed to increase ER alpha association with the more proximal promoter region. Finally, E-2 administration led to significant changes in the mRNA expression of several ER coregulators in a brain-region dependent manner. Taken together, these data indicate that, in the hypothalamus and preoptic area of female mice, early responses to E-2 treatment involve highly specific changes in chromatin structure, dependent on cell group, gene, histone modification studied, promoter/enhancer site and time following E-2.
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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, Delaere C, du Pree T, Favart D, Forthomme L, Giammanco A, Hollar J, Lemaitre V, Liao J, Militaru O, Nuttens C, Pagano D, Pin A, Piotrzkowski K, Popov A, Selvaggi M, 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, Jorge LS, Sznajder A, Manganote EJT, Pereira AV, Anjos TS, Bernardes CA, Dias FA, Tomei TRFP, Gregores EM, Lagana C, Marinho F, Mercadante PG, Novaes SF, Padula SS, Genchev V, Iaydjiev P, Piperov S, Rodozov M, Stoykova S, Sultanov G, Tcholakov V, Trayanov R, 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 J, Wang X, Wang Z, Xiao H, Xu M, 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 CAC, Gomez JP, Moreno BG, Sanabria JC, Godinovic N, Lelas D, Plestina R, Polic D, Puljak I, Antunovic Z, Kovac M, Brigljevic V, Duric S, 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, Assran Y, Kamel AE, Mahmoud MA, Mahrous A, 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, Korpela A, Tuuva T, Besancon M, Choudhury S, 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, Bianchini L, Bluj M, Busson P, Charlot C, Daci N, Dahms T, Dalchenko M, Dobrzynski L, Florent A, de Cassagnac RG, Haguenauer 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, Bodin 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, Beauceron S, Beaupere N, Boudoul G, Brochet S, Chasserat J, Chierici R, Contardo D, Depasse P, El Mamouni H, Fay J, Gascon S, Gouzevitch M, Ille B, Kurca T, Lethuillier M, Mirabito L, Perries S, Sgandurra L, Sordini V, Tschudi Y, Vander Donckt M, Verdier P, Viret S, Tsamalaidze Z, Autermann C, Beranek S, Calpas B, Edelhoff M, Feld L, Heracleous N, Hindrichs O, Klein K, Merz J, 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, 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, Martin MA, Asin I, Bartosik N, Behr J, Behrenhoff W, Behrens U, Bergholz M, Bethani A, Borras K, Burgmeier A, Cakir A, Calligaris L, Campbell A, Costanza F, Pardos CD, Dorland T, Eckerlin G, Eckstein D, Flucke G, Geiser A, Glushkov I, Gunnellini P, Habib S, Hauk J, Hellwig G, Jung H, Kasemann M, Katsas P, Kleinwort C, Kluge H, Kramer M, 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, Raspereza A, Cipriano PMR, Riedl C, Ron E, Salfeld-Nebgen J, Schmidt R, Schoerner-Sadenius T, Sen N, Stein M, Walsh R, Wissing C, Blobel V, Enderle H, Erfle J, Gebbert U, Gorner M, Gosselink M, Haller J, Heine K, Hoing RS, Kaussen G, Kirschenmann H, Klanner R, Lange J, 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, Vanelderen L, Barth C, Baus C, Berger J, Boser C, Chwalek T, De Boer W, Descroix A, Dierlamm A, Feindt M, Guthoff M, Hackstein C, Hartmann F, Hauth T, Heinrich M, Held H, Hoffmann KH, Husemann U, Katkov I, Komaragiri JR, Kornmayer A, Pardo PL, Martschei D, Mueller S, Muller T, Niegel M, Nurnberg A, Oberst O, Ott J, Quast G, Rabbertz K, Ratnikov F, Ratnikova N, Rocker S, Schilling FP, Schott G, Simonis HJ, Stober FM, Troendle D, 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, Gouskos L, Mertzimekis TJ, 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, Radics B, 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, Beri SB, Bhatnagar V, Dhingra N, Gupta R, Kaur M, Mehta MZ, Mittal M, Nishu N, Saini LK, 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, Abdulsalam A, Dutta D, Kailas S, Kumar V, Mohanty AK, Pant LM, Shukla P, Topkar A, Aziz T, Chatterjee RM, Ganguly S, Guchait M, Gurtu A, 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, Hesari H, 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, 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, Potenza R, Tricomi A, Tuve C, Barbagli G, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Frosali S, Gallo E, Gonzi S, Lenzi P, Meschini M, Paoletti S, Sguazzoni G, Tropiano A, Benussi L, Bianco S, Fabbri F, Piccolo D, Fabbricatore P, Musenich R, Tosi S, Benaglia A, De Guio F, Di Matteo L, Fiorendi S, Gennai S, Ghezzi A, Govoni P, Lucchini MT, Malvezzi S, Manzoni RA, Martelli A, Massironi 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, Bellan P, Biasotto M, Bisello D, Branca A, Carlin R, Checchia P, Dorigo T, Fanzago F, Galanti M, Gasparini F, Gasparini U, Giubilato P, Gonella F, Gozzelino A, Kanishchev K, Lacaprara S, Lazzizzera I, Margoni M, Meneguzzo AT, Montecassiano F, Pazzini J, Pozzobon N, Ronchese P, Sgaravatto M, Simonetto F, Torassa E, Tosi M, Zotto P, 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, Boccali T, Broccolo G, Castaldi R, D'Agnolo RT, Dell'Orso R, Fiori F, Foa L, Giassi A, Kraan A, Ligabue F, Lomtadze T, Martini L, Messineo A, Palla F, Rizzi A, Serban AT, Spagnolo P, Squillacioti P, Tenchini R, Tonelli G, Venturi A, Verdini PG, Vernieri C, Barone L, Cavallari F, Del Re D, Diemoz M, Fanelli C, Grassi M, Longo E, Margaroli F, Meridiani P, Micheli F, Nourbakhsh S, Organtini G, Paramatti R, Rahatlou S, Soffi L, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Biino C, Cartiglia N, Casasso S, Costa M, Dellacasa G, 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, Kim TY, Nam SK, Chang S, Kim DH, Kim GN, Kim JE, Kong DJ, 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, Bell AJ, Butler PH, Doesburg R, Reucroft S, Silverwood H, Ahmad M, Asghar MI, Butt J, Hoorani HR, Khalid S, Khan WA, Khurshid T, Qazi S, Shah MA, 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, David A, Faccioli P, Parracho PGF, Gallinaro M, Antunes JR, Seixas J, Varela J, Vischia P, Bunin P, Gavrilenko M, Golutvin I, Gorbunov I, Kamenev A, Karjavin V, Konoplyanikov V, Kozlov G, 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, Dubinin M, Dudko L, Ershov A, Gribushin A, Klyukhin V, Kodolova O, Lokhtin I, Markina A, 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, 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'Enterria D, Dabrowski A, De Roeck A, De Visscher S, 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Measurement of the ratio of the inclusive 3-jet cross section to the inclusive 2-jet cross section in pp collisions at root s=7 TeV and first determination of the strong coupling constant in the TeV range
EUROPEAN PHYSICAL JOURNAL C 2013 OCT 19; 73(10):? Article 2604
A measurement is presented of the ratio of the inclusive 3-jet cross section to the inclusive 2-jet cross section as a function of the average transverse momentum, < p(T1,2)>, of the two leading jets in the event. The data sample was collected during 2011 at a proton-proton centre-of-mass energy of 7 TeV with the CMS detector at the LHC, corresponding to an integrated luminosity of 5.0 fb(-1). The strong coupling constant at the scale of the Z boson mass is determined to be alpha(S)(M-Z) = 0.1148 +/- 0.0014 (exp.) +/- 0.0018 (PDF) +/- 0.0050 (theory), by comparing the ratio in the range 0.42 < < p(T1,2)> < 1.39 TeV to the predictions of perturbative QCD at next-to-leading order. This is the first determination of alpha(S)(M-Z) from measurements at momentum scales beyond 0.6 TeV. The predicted ratio depends only indirectly on the evolution of the parton distribution functions of the proton such that this measurement also serves as a test of the evolution of the strong coupling constant. No deviation from the expected behaviour is observed.
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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, Friis E, Grothe M, Hall-Wilton R, Herndon M, Herve A, Kaadze K, Klabbers P, Klukas J, Lanaro A, Loveless R, Mohapatra A, Mozer MU, Ojalvo I, Pierro GA, Polese G, Ross I, Savin A, Smith WH, Swanson J
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Search for gluino mediated bottom- and top-squark production in multijet final states in pp collisions at 8 TeV
PHYSICS LETTERS B 2013 OCT; 725(4-5):243-270
A search for supersymmetry is presented based on events with large missing transverse energy, no isolated electron or muon, and at least three jets with one or more identified as a bottom-quark jet. A simultaneous examination is performed of the numbers of events in exclusive bins of the scalar sum of jet transverse momentum values, missing transverse energy, and bottom-quark jet multiplicity. The sample, corresponding to an integrated luminosity of 19.4 fb(-1), consists of proton-proton collision data recorded at a center-of-mass energy of 8 TeV with the CMS detector at the LHC in 2012. The observed numbers of events are found to be consistent with the standard model expectation, which is evaluated with control samples in data. The results are interpreted in the context of two simplified supersymmetric scenarios in which gluino pair production is followed by the decay of each gluino to an undetected lightest supersymmetric particle and either a bottom or top quark-antiquark pair, characteristic of gluino mediated bottom- or top-squark production. Using the production cross section calculated to next-to-leading-Order plus next-to-leading-logarithm accuracy, and in the limit of a massless lightest supersymmetric particle, we exclude gluinos with masses below 1170 GeV and 1020 GeV for the two scenarios, respectively. (C) 2013 CERN. Published by Elsevier B.V. All rights reserved.
Boisson B, Wang CH, Pedergnana V, Wu L, Cypowyj S, Rybojad M, Belkadi A, Picard C, Abel L, Fieschi C, Puel A, Li XX, Casanova JL
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An ACT1 Mutation Selectively Abolishes Interleukin-17 Responses in Humans with Chronic Mucocutaneous Candidiasis
IMMUNITY 2013 OCT 17; 39(4):676-686
Patients with inborn errors of interleukin-17F (IL-17F) or IL-17RA display chronic mucocutaneous candidiasis (CMC). We report a biallelic missense mutation (T536I) in the adaptor molecule ACT1 in two siblings with CMC. The mutation, located in the SEFIR domain, abolished the homotypic interaction of ACT1 with IL-17 receptors, with no effect on homo-dimerization. The patients' fibroblasts failed to respond to IL-17A and IL-17F, and their T cells to IL-17E. By contrast, healthy individuals homozygous for the common variant D10N, located in the ACT1 tumor necrosis factor receptor-associated factor-interacting domain and previously associated with psoriasis, had impaired, but not abolished, responses to IL-17 cytokines. SEFIR-independent interactions of ACT1 with other proteins, such as CD40, heat shock protein 70 (HSP70) and HSP90, were not affected by the T536I mutation. Overall, human IL-17A and IL-17F depend on ACT1 to mediate protective mucocutaneous immunity. Moreover, other ACT1-dependent IL-17 cytokines seem to be largely redundant in host defense.
Takagi J, Itabashi T, Suzuki K, Kapoor TM, Shimamoto Y, Ishiwata S
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Using Micromanipulation to Analyze Control of Vertebrate Meiotic Spindle Size
CELL REPORTS 2013 OCT; 5(1):44-50
The polymerization/depolymerization dynamics of microtubules (MTs) have been reported to contribute to control of the size and shape of spindles, but quantitative analysis of how the size and shape correlate with the amount and density of MTs in the spindle remains incomplete. Here, we measured these parameters using 3D microscopy of meiotic spindles that self-organized in Xenopus egg extracts and presented a simple equation describing the relationship among these parameters. To examine the validity of the equation, we cut the spindle into two fragments along the pole-to-pole axis by micromanipulation techniques that rapidly decrease the amount of MTs. The spheroidal shape spontaneously recovered within 5 min, but the size of each fragment remained small. The equation we obtained quantitatively describes how the spindle size correlates with the amount of MTs while maintaining the shape and the MT density.
Lindenbach BD, Rice CM
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The ins and outs of hepatitis C virus entry and assembly
NATURE REVIEWS MICROBIOLOGY 2013 OCT; 11(10):688-700
Hepatitis C virus, a major human pathogen, produces infectious virus particles with several unique features, such as an ability to interact with serum lipoproteins, a dizzyingly complicated process of virus entry, and a pathway of virus assembly and release that is closely linked to lipoprotein secretion. Here, we review these unique features, with an emphasis on recent discoveries concerning virus particle structure, virus entry and virus particle assembly and release.
Xue JZ, Woo EM, Postow L, Chait BT, Funabiki H
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Chromatin-Bound Xenopus Dppa2 Shapes the Nucleus by Locally Inhibiting Microtubule Assembly
DEVELOPMENTAL CELL 2013 OCT 14; 27(1):47-59
Nuclear shape and size vary between species, during development, and in many tissue pathologies, but the causes and effects of these differences remain poorly understood. During fertilization, sperm nuclei undergo a dramatic conversion from a heavily compacted form into decondensed, spherical pronuclei, accompanied by rapid nucleation of microtubules from centrosomes. Here we report that the assembly of the spherical nucleus depends on a critical balance of microtubule dynamics, which is regulated by the chromatin-binding protein Developmental pluripotency-associated 2 (Dppa2). Whereas microtubules normally promote sperm pronuclear expansion, in Dppa2-depleted Xenopus egg extracts excess microtubules cause pronuclear assembly defects, leading to abnormal morphology and disorganized DNA replication. Dppa2 inhibits microtubule polymerization in vitro, and Dppa2 activity is needed at a precise time and location during nascent pronuclear formation. This demonstrates a strict spatiotemporal requirement for local suppression of microtubules during nuclear formation, fulfilled by chromatin-bound microtubule regulators.
Kalashikam RR, Battula KK, Kirlampalli V, Friedman JM, Nappanveettil G
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Obese Locus in WNIN/Obese Rat Maps on Chromosome 5 Upstream of Leptin Receptor
PLOS ONE 2013 OCT 21; 8(10):? Article e77679
WNIN/Obese (WNIN/Ob) rat a new mutant model of metabolic syndrome was identified in 1996 from an inbred Wistar rat strain, WNIN. So far several papers are published on this model highlighting its physical, biochemical and metabolic traits. WNIN/Ob is leptin resistant with unaltered leptin or its receptor coding sequences - the two well-known candidate genes for obesity. Genotyping analysis of F2 progeny (raised from WNIN/Ob x Fisher - 344) in the present study localized the mutation to a recombinant region of 14.15cM on chromosome 5. This was further corroborated by QTL analysis for body weight, which narrowed this region to 4.43 cM with flanking markers D5Rat256 & D5Wox37. Interval mapping of body weight QTL shows that the LOD score peak maps upstream of leptin receptor and shows an additive effect suggesting this as a novel mutation and signifying the model as a valuable resource for studies on obesity and metabolic syndrome.
Tavares A, Miragaia M, Rolo J, Coelho C, de Lencastre H
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High prevalence of hospital-associated methicillin-resistant Staphylococcus aureus in the community in Portugal: evidence for the blurring of community-hospital boundaries
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES 2013 OCT; 32(10):1269-1283
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of infection in the community (CA-MRSA), but in spite of its relevance, no data exist concerning its epidemiology in Portugal. In this study, we aimed to evaluate the prevalence, population structure, and origin of MRSA in the Portuguese community. A total of 527 isolates, both methicillin-susceptible S. aureus (MSSA) and MRSA, were collected from individuals with no healthcare-related risk factors attending 16 healthcare institutions in Portugal. Isolates were characterized for the presence of mecA, Panton-Valentine leukocidin (PVL), and arginine catabolic mobile element (ACME), and by staphylococcal cassette chromosome mec (SCCmec) typing, pulsed-field gel electrophoresis (PFGE), spa, and multilocus sequence typing (MLST). Susceptibility to a panel of 13 antibiotics was tested. Isolates relatedness was analyzed by goeBURST and BURP. We found a high frequency (21.6 %) of MRSA in the community. However, only 11.4 % of the isolates belonged to typical CA-MRSA epidemic clones (USA300, USA400, USA700, Southwest Pacific, European, and ST398). The remaining isolates, which constituted the great majority (88.6 %), belonged to hospital-associated MRSA (HA-MRSA) epidemic clones, namely, to the EMRSA-15 clone (77.2 %). PVL was rare and carried by 17 isolates only (five MRSA and 12 MSSA). In the whole collection, some MRSA and MSSA were highly related. The high frequency of MRSA in the community in Portugal seems to result mainly from dissemination from the hospital. They might also have emerged from an extant MSSA population, by SCCmec acquisition, or MRSA clonal introduction from abroad.