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Found 37684 matches. Displaying 5521-5530
Mairesse J, Gatta E, Reynaert ML, Marrocco J, Morley-Fletcher S, Soichot M, Deruyter L, Van Camp G, Bouwalerh H, Fagioli F, Pittaluga A, Allorge D, Nicoletti F, Maccari S
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Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats
PSYCHONEUROENDOCRINOLOGY 2015 DEC; 62(?):36-46
Oxytocin receptors are known to modulate synaptic transmission and network activity in the hippocampus, but their precise function has been only partially elucidated. Here, we have found that activation of presynaptic oxytocin receptor with the potent agonist, carbetocin, enhanced depolarization-evoked glutamate release in the ventral hippocampus with no effect on GABA release. This evidence paved the way for examining the effect of carbetocin treatment in "prenatally restraint stressed" (PRS) rats, i.e., the offspring of dams exposed to repeated episodes of restraint stress during pregnancy. Adult PRS rats exhibit an anxious/depressive-like phenotype associated with an abnormal glucocorticoid feedback regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and, remarkably, with a reduced depolarization-evoked glutamate release in the ventral hippocampus. Chronic systemic treatment with carbetocin (1 mg/kg, i.p., once a day for 2-3 weeks) in PRS rats corrected the defect in glutamate release, anxiety- and depressive-like behavior, and abnormalities in social behavior, in the HPA response to stress, and in the expression of stress-related genes in the hippocampus and amygdala. Of note, carbetocin treatment had no effect on these behavioral and neuroendocrine parameters in prenatally unstressed (control) rats, with the exception of a reduced expression of the oxytocin receptor gene in the amygdala. These findings disclose a novel function of oxytocin receptors in the hippocampus, and encourage the use of oxytocin receptor agonists in the treatment of stress-related psychiatric disorders in adult life. (C) 2015 Elsevier Ltd. All rights reserved.
Gleicher N, Vega MV, Darmon SK, Weghofer A, Wu YG, Wang Q, Zhang L, Albertini DF, Barad DH, Kushnir VA
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Live-birth rates in very poor prognosis patients, who are defined as poor responders under the Bologna criteria, with nonelective single embryo, two-embryo, and three or more embryos transferred
FERTILITY AND STERILITY 2015 DEC; 104(6):1435-1441
Objective: To determine live-birth rates (LBRs) at various ages in very poor prognosis patients, who are defined as poor responders under the Bologna criteria. Design: Retrospective cohort study. Setting: Academically affiliated private fertility center. Patient(s): Among 483 patients, who under the Bologna criteria (three or fewer oocytes, >40 years of age, and/or antimullerian hormone [AMH] <1.1 ng/mL [2/3 criteria minimum]) were poor responders, 278 (381 fresh IVF cycles) qualified for the study because they had at least one embryo on day 3 for transfer. Intervention(s): IVF cycles in women with low functional ovarian reserve, involving androgen and CoQ10 supplementation and ovarian stimulation with daily gonadotropin dosages of 300-450 IU of FSH and 150 IU of hMG in microdose agonist cycles. Main Outcome Measure(s): Age-specific LBRs per ET. Result(s): Ages did not differ between nonelective (ne) single ET (SET), ne2-ET, and neR3-ET cycles (41.3 +/- 3.9, 41.7 +/- 3.1, and 42.4 +/- 2.1 years, respectively). Patients with neSETs demonstrated significantly lower AMH and higher FSH levels and required higher gonadotropin dosages than ne2-ET and neR3-ET patients. LBRs declined with age. Above age 42, three or more embryos are required to achieve reasonable LBRs and two or more to avoid futility under American Society for Reproductive Medicine (ASRM) guidelines. Conclusion(s): Very poor prognosis patients can still achieve acceptable pregnancy rates at least till their mid-40s if they reach ET. The degree to which egg donation is emphasized as the only treatment option in such patients, therefore, requires reconsideration. Above age 42, at least two, and preferably three embryos, are however required to exceed futility, as defined by ASRM. (C) 2015 by American Society for Reproductive Medicine.
Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, Eroe J, Friedl M, Fruhwirth R, Ghete VM, Hartl C, Hormann N, Hrubec J, Jeitler M, Kiesenhofer W, Knunz V, Krammer M, Kratschmer I, Liko D, Mikulec I, Rabady D, Rahbaran B, Rohringer H, Schofbeck R, Strauss J, Treberer-Treberspure W, Waltenberger W, Wulz CE, Mossolov V, Shumeiko N, Gonzalez JS, Alderweireldt S, Bansal 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, Blekman F, Blyweert S, D'Hondt J, Daci N, Heracleous N, Keaveney J, Lowette S, Maes M, Olbrechts A, Python Q, Strom D, Tavernier S, Van Doninck W, Van Mulders P, Van Onsem GP, Villella I, Caillol C, Clerbaux B, De Lentdecker G, Dobur D, Favart L, Gay APR, Grebenyuk A, Leonard A, Mohammadi A, Pernie L, Randle-conde A, Reis T, Seva T, Thomas L, Vander Velde C, Vanlaer P, Wang J, Zenoni F, Adler V, Beernaert K, Benucci L, Cimmino A, Costantini S, Crucy S, Fagot A, Garcia G, Mccartin J, Rios AAO, Poyraz D, Ryckbosch D, Salva S, Sigamani M, Strobbe N, Thyssen F, Tytgat M, Yazgan E, Zaganidis N, Basegmez S, Beluffi C, Bruno G, Castello R, Caudron A, Ceard L, Da Silveira GG, Delaere C, du Pree T, Favart D, Forthomme L, Giammanco A, Hollar J, Jafari A, Jez P, Komm M, Lemaitre V, Nuttens C, Pagano D, Perrini L, Pin A, Piotrzkowski KK, Popov A, Quertenmont LL, Selvaggi M, Marono MV, Garcia JMV, Beliy N, Caebergs T, Daubie E, Hammad GH, Aida WL, Alves GA, Brito L, Martins MC, Martins TD, Molina J, Herrera CM, Poi ME, Teles PR, Carvalho W, Chinellato J, Custodio A, Da Costa EM, Damiao DD, Martins CD, De Souza SF, Malbouisson H, Figueiredo DM, Mundim L, Nogima H, Da Silva WLP, Santaolalla J, Santoro A, Sznajder A, Manganote EJT, Pereira AV, Bernardes CA, Dogra S, Tomei TRFP, Gregores EM, Mercadante PG, Novaes SF, Padula SS, Aleksandrov A, Genchey V, Hadjiiska R, Iaydjiev P, Marinov A, Piperov S, Rodozov M, 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Givemaud A, Gras P, de Monchenault GH, Jarry P, Locci E, Malcles J, Rander J, Rosowsky A, Titov M, Baffioni S, Beaudette F, Busson P, Chapon E, Chariot C, Dahms T, Dobrzyns L, Filipovic N, Florent A, de Cassagnac RG, Mastrolorenzo L, Mine P, Naranjo IN, Nguyen M, Ochando C, Ortona G, Paganini P, Regnard S, Salerno R, Sauvan JB, Sirois Y, Veelken C, Yilmaz Y, Zabi A, Agram JL, Andrea J, Aubin A, Bloch D, Brom JM, Chabert EC, Collard C, Conte E, Fontaine JC, Gele D, Goerlach U, Goetzmann C, Le Bilian AC, Skovpen K, Van Hove P, Gadrat S, Beauceron S, Beaupere N, Bernet C, Boudou G, Bouvier E, Brochet S, 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, Kurca T, Lethuillier M, Mirabito L, Pequegnot AL, Perries S, Alvarez JDR, Sabes D, Sgandurra L, Sordini V, Vander Donckt M, Verdier P, Viret S, Xiao H, Tsamalaidze Z, Autermann C, Beranek S, Bontenackels M, Edelhoff M, Feld L, Heister A, Klein K, Lipinski M, Ostapchuk A, Preuten M, Raupach F, Sammet J, Schael S, Schulte JF, Weber H, Wittmer B, Zhukov V, Ata M, Brodski M, Dietz-Laursonn E, Duchardt D, Erdmann M, Fischer R, Gueth 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, Reithler H, Schmitz SA, Sonnenschein L, Teyssier D, Thueer S, Cherepanov V, Erdogan Y, Fluegge G, Geenen H, Geisler M, Ahmad WH, Hoehle F, Kargoll B, Kress T, Kuessel Y, Kuensken A, Lingemann J, Nowack A, Nugent IM, Pistone C, Pooth O, Stahl A, Martin MA, Asin I, Bartosik N, Behr J, Behrens U, Bell AJ, Bethani A, 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, Garcia JG, Geiser A, Gizhko A, Gunnellini P, Hauk J, Hempel M, Jung HH, Kalogeropoulos A, Karacheban O, Kasemann M, Katsas P, Kieseler J, Kleinwort C, Korol I, Kruecker D, Lange W, Leonard J, 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Montanari A, Navarria FL, Perrotta A, Rossi AM, Rovelli T, Siroli GP, Tosi N, Travaglini R, Albergo S, Cappello G, Chiorboli M, Costa S, Giordano F, Potenza R, Tricomi A, Tuve C, Barbagli G, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Gallo E, Gonzi S, Gori V, Lenzi P, Meschini M, Paoletti S, Sguazzoni G, Tropiano A, Benussi L, Bianco S, Fabbri F, Piccolo D, Ferretti R, Ferro F, Lo Vetere M, Robutti E, Tosi S, Dinardo ME, Fiorendi S, Gennai S, Gerosa R, Ghezzi A, Govoni P, Lucchini MT, Malvezzi S, Manzoni RA, Martelli A, Marzocchi B, Menasce D, Moroni L, Paganoni M, Pedrini D, Ragazzi S, Redaelli N, de Fatis TT, Buontempo S, Cavallo N, Di Guida S, Fabozzi F, Iorio AOM, Lista L, Meola S, Merola M, Paolucci P, Azzi P, Bacchetta N, Bellato M, Dall'Osso M, Dorigo T, Fantinel S, Gonella F, Gozzelino A, Gulmini M, Lacaprara S, Margoni M, Meneguzzo AT, Montecassiano F, Pazzini J, Pegoraro M, Pozzobon N, Ronchese P, Sgaravatto M, Simonetto F, Torassa E, Tosi M, Vanini S, Ventura S, Zotto 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Bunkowski K, Cwiok M, Dominik W, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Olszewski M, Bargassa P, Silva CBDE, Faccioli P, Parracho PGF, Gallinaro M, Iglesias LL, 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, Laney A, Malakhov A, Matveev V, Moisenz P, Palichik V, Perelygin V, Shmatov 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, Vorobyev A, Andreev Y, Dermenev A, Gninenko S, Golubev N, Kirsanov M, Krasnikov N, Pashenkov A, Tlisov D, Toropin A, Epshteyn V, Gavrilov V, Lychkovskaya N, Popov V, Pozdnyakov I, 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, Ershov A, Gribushin A, Khein L, Klyukhin V, Kodolova O, 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GI, Wardle N, Woehri HK, Wollny H, Zeuner WD, Bertl W, Deiters K, Erdmann W, Horisberger R, Ingram Q, Kaestli HC, Kotlinski D, Langenegger U, Renker D, Rohe T, Bachmair F, Baeni L, Bianchini L, Buchmann MA, Casal B, Chanon N, Dissertori G, Dittmar M, Donega M, Duenser M, Eller P, Grab C, Hits D, Hoss J, Kasieczka G, Lustermann W, Mangano B, Marini AC, Marionneau M, del Arbol PMR, Masciovecchio M, Meister D, Mohr N, Musella P, Nageli C, Nessi-Tedaldi F, Pandolfi F, Pauss F, Perrozzi L, Peruzzi M, Quittnat M, Rebane L, Rossini M, Starodumov A, Takahashi M, Theofilatos K, Wallny R, Weber HA, Amsler C, Canelli MF, Chiochia V, De Cosa A, Hinzmann A, Hreus T, Kilminster B, Lange C, Ngadiuba J, Pinna D, Robmann P, Ronga FJ, Taroni S, Yang Y, Cardaci M, Chen KH, Ferro C, Kuo CM, Lin W, Lu YJ, Volpe R, Yu SS, Bartek R, Chang P, Chang YH, Chao Y, Chen KF, Chen PH, Dietz C, Grundler U, Hou WS, Liu YF, Lu RS, Moya MM, Petrakou E, Tsai JF, Tzeng YM, Asavapibhop B, Singh G, Srimanobhas N, Suwonjandee N, Adiguzel A, Bakirci MN, Cerci S, Dozen C, Dumanoglu I, Eskut E, Girgis S, Gokbulut G, Guler Y, Gurpinar E, Hos I, Kangal EE, Topaksu AK, Onengut G, Ozdemir K, Ozturk S, Polatoz A, Cerci DS, Tali B, Topakli H, Vergili M, Zorbilmez C, Akin IV, Bilin B, Bilmis S, Gamsizkan H, Isildak B, Karapinar G, Ocalan K, Sekmen S, Surat UE, Yalvac M, Zeyrek M, Albayrak EA, Guelmez E, Kaya M, Kaya O, Yetkin T, Cankocak K, Vardarli FI, Levchuk L, Sorokin P, 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 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, Tomalin IR, Williamz T, Womersley WJ, Worm SD, Baber M, Bainbridge R, Buchmuller O, Burton D, Colling D, Cripps N, Dauncey P, Davies G, Della Negra M, Dunne R, Elwood A, Ferguson W, Fulcher J, Futyan D, Hall G, Iles G, Jarvis M, Karapostoli G, Kenzie M, Lane R, Lucas R, Lyons L, Magnan AM, Malik S, Mathias B, Nash J, Nikitenko A, Pela J, Pesaresi M, Petridis K, Raymond DM, Rogerson S, Rose A, Seez C, Sharp P, Tapper AA, 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, Dittmann J, Hatakeyama K, Kasmi A, Liu H, Pastika N, Scarborough T, Wu Z, Charaf O, Cooper SI, Henderson C, Rumerio P, Avetisyan A, Bose T, Fantasia C, Lawson P, Richardson C, Rohlf J, St John J, Sulak L, Alimena J, Berry E, Bhattacharya S, Christopher G, Cutts D, Demiragli Z, Dhingra N, Ferapontov A, Garabedian A, Heintz U, Laird E, Landsberg G, Mao Z, Narain M, Sagir S, Sinthuprasith T, Speer T, Swanson J, Breedon R, Breto G, Sanchez MCD, Chauhan S, Chertok M, Conway J, Conway R, Cox PT, Erbacher R, Gardner M, Ko W, Lander R, 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, Rakness G, 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, Sumowidagdo S, 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, Palmer C, Pieri M, Sani M, Sharma V, Simon S, Tadel M, Tu Y, Vartak A, Welke C, Wuerthwein F, Yagil A, Della Porta GZ, Barge D, Bradmiller-Feld J, Campagnari C, Danielson T, Dishaw A, Dutta V, Flowers K, Sevilla MF, Geffert R, George C, Golf F, Gouskos L, Incandela J, Justus C, Mccoll N, Mullin SD, Richman J, Stuart D, To W, West C, Yoo J, Apresyan A, Bornheim A, Bunn J, Chen Y, Duarte J, Mott A, Newman HB, Pena C, Pierini M, Spiropulu M, Vlimant JR, Wilkinson R, Xie S, Zhu RY, Azzolini V, Calamba A, Carlson B, Ferguson T, Iiyama Y, Paulini M, Russ J, Vogel H, Vorobiev I, Cumalat JP, Ford WT, Gaz A, Krohn M, Lopez EL, Nauenberg U, Smith JG, Stenson K, Wagner SR, Alexander J, Chatterjee A, Chaves J, Chu J, Dittmer S, Eggert N, Mirman N, Kaufman GN, Patterson JR, Ryd A, Salvati E, Skinnari L, Sun W, Teo WD, Thom J, Thompson J, Tucker J, Weng Y, Winstrom L, Wittich P, Winn D, Abdullin S, Albrow M, Anderson J, Apollinari G, Bauerdick LAT, Beretvas A, Berryhill J, Bhat PC, Bolla G, Burkett K, Butler JN, Cheung HWK, Chlebana F, Cihangir S, Elvira VD, Fisk I, Freeman J, Gottschalk E, Gray L, Green D, Gruenendahl S, Gutsche O, Hanlon J, Hare D, Harris RM, Hirschauer J, Hooberman B, Jindariani S, Johnson M, Joshi U, Klima B, Kreis B, Kwan S, Linacre J, Lincoln D, Lipton R, Liu T, De Sa RL, Lykken J, Maeshima K, Marraffino JM, Outschoom VIM, Maruyama S, Mason D, McBride P, Merke P, Mishra K, Mrenna S, Nahn S, Newman-Holmes C, O'Dell V, Prokofyev O, Sexton-Kennedy E, Soha A, Spalding WJ, Spiegel L, Taylor LL, Tkacyk S, Tran NV, Uplegger L, Vaandering EW, Vidal R, Whitbeck A, Whitmore J, Yang F, Costa D, Avery P, Bortignon P, Bourilkov D, Carver M, Curry D, Das S, De Gruttola M, Di Giovanni GP, Field RD, Fisher M, Furic IK, Hugon J, Konigsberg J, Korytov A, Kypreos T, Low JF, Matchev K, Mei H, Milenovic P, Mitselmakher G, Muniz L, Rinkevicius A, Shchutska L, Snowball M, Sperka D, Yelton J, Zakaria M, Hewamanage S, Linn S, Markowitz P, Martinez G, Rodriguez JL, Adams JR, Adams T, Askew A, Bochenek J, Diamond B, Haas J, Hagopian S, Hagopian V, Johnson KF, Prosper H, Veeraraghavan V, Weinberg M, Baarmand MM, Hohlmann M, Kalakhety H, Yumiceva F, Adams MR, Apanasevich L, Berry D, Belts 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, Bilki B, Clarida W, Dilsiz K, Haytmyradov M, Khristenko V, Merlo JP, Mermerkaya H, Mestvirishvili A, Moeller A, Nachtman J, Ogul H, Onel Y, Ozok F, Penzo A, Rahmat R, Sen S, Tan P, Tiras E, Wetzel J, Yi K, Anderson I, Barnett BA, Blumenfeld B, Bolognesi S, Fehling D, Gritsan AV, Maksimovic P, Martin C, Swartz M, Xiao M, Baringer P, Bean A, Benelli G, Bruner C, Gray J, Kenny RR, Majumder D, Malek M, Murray M, Noonan D, Sanders S, Sekaric J, Stringer R, Wang Q, Wood JS, Chakaberia I, Ivanov A, Kaadze K, Khali S, Makouski M, Maravin Y, Saini LK, Skhirtladze N, Svintradze I, Gronberg J, Lange D, Rebassoo F, Wright D, Baden A, Belloni A, Calvert B, Eno SC, Gomez JJA, Hadley NJ, Jabeen S, Kellogg RG, Kolberg T, Lu Y, Mignerey AC, Pedro K, Skuja A, Tonjes MB, Tonwar SC, Apyan A, Barbieri R, Bierwagen K, Busza W, Cali IA, Di Matteo L, Ceballos GG, Goncharov M, Gulhan D, Klute M, Lai YS, Lee YJ, Levin A, Luckey PD, Paus C, Ralph D, Roland C, Roland G, Stephans GSF, Sumorok K, Velicanu D, Veverka J, Wyslouch B, Yang M, Zanetti M, Zhukova V, Dahmes B, Gude A, Kao SC, Klapoetke K, Kubota Y, Mans J, Nourbakhsh S, Rusack R, Singovsky A, Tambe N, Turkewitz J, Acosta JG, Oliveros S, Avdeeva E, Bloom K, Bose S, Claes DR, Dominguez A, Suarez RG, Keller J, Knowlton D, Kravehenko I, Lazo-Flores J, Meier F, Ratnikov F, Snow GR, Zvada M, Dolen J, Godshalk A, Iashvili I, Kharchilava A, Kumar A, Rappoccio S, Alverson G, Barberis E, Baumgarte D, Chasco M, Massironi A, Morse DM, Nash D, Orimoto T, Trocino D, Wang RJ, Wood D, Zhang J, Hahn KA, Kubik A, Mucia N, Odell N, Pollack B, Pozdnyakov A, Schmitt M, Stoynev S, Sung K, Velasco M, Won S, Brinkerhoff A, Chan KM, Drozdetskiy A, Hildreth M, Jessop C, Karmgard DJ, Kellams N, Lannon K, Lynch S, Marinelli N, Musienko Y, Pearson T, Planer M, Ruchti R, Smith G, 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, Luo W, Puigh D, Rodenburg M, Winer BL, Wolfe H, Wulsin HW, Driga O, Elmer P, Hardenbrook J, Hebda P, Koay SA, Lujan P, Marlow D, Medvedeva T, Mooney M, Olsen J, Piroue P, Quan X, Saka H, Stickland D, Tully C, Werner JS, Zuranski A, Brownson E, Malik S, Mendez H, Vargas JER, Barnes VE, Benedetti D, Bortoletto D, Gutay L, Hu Z, Jha MK, Jones M, Jung K, Kress M, Leonardo N, Miller DH, Neumeister N, Primavera F, Radburn-Smith BC, Shi X, Shipsey I, Silvers D, Svyatkovskiy A, Wang F, Xie W, Xu L, Zablocki J, Parashar N, Stupak J, Adair A, Akgun B, Ecklund KM, Geurts FJM, Li W, Michlin B, Padley BP, Redjimi R, Roberts J, Zabel J, Betchart B, Bodek A, De Barbaro P, Demina R, Eshaq Y, Ferbel T, Galanti M, Garcia-Bellido A, Goldenzweig P, Han J, Harel A, Hindrichs O, Khukhunaishvili A, Korjenevski S, Petrillo G, Verzetti M, Vishnevskiy D, Ciesielski R, Demortier L, Goulianos K, Mesropian C, Arora S, Barker A, Chou JP, Contreras-Campana C, Contreras-Campana E, Duggan D, Ferencek D, Gershtein Y, Gray R, Halkiadakis E, Hidas D, Kaplan S, Lath A, Panwalkar S, Park M, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Rose K, Spanier S, York A, Bouhali O, Hernandez AC, Dalchenko M, De Mattia M, Dildick S, Eusebi R, Flanagan W, Gilmore J, Kamon T, Khotilovich V, Krutelyov V, Montalvo R, Osipenkov I, Pakhotin Y, Patel R, Perloff A, Roe J, Rose A, Safonov A, Suarez I, Tatarinov A, Ulmer KA, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero PR, Faulkner J, Kovitanggoon K, Kunori S, Lee SW, Libeiro T, Volobouev I, Appelt E, Delannoy AG, Greene S, Gurrola A, Johns W, Maguire C, Mao Y, Melo A, Sharma M, Sheldon P, Snook B, Tuo S, Velkovska J, Arenton MW, Boutle S, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Lin C, Neu C, Wolfe E, Wood J, Clarke C, Harr R, Karchin PE, Don CKK, Lamichhane P, Sturdy J, Belknap DA, Carlsmith D, Cepeda M, Dasu S, Dodd L, Duric S, Friis E, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Lanaro A, Lazaridis C, Levine A, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ross I, Sarangi T, Savin A, Smith WH, Taylor D, Vuosalo C, Woods N
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Production of leading charged particles and leading charged-particle jets at small transverse momenta in pp collisions at root s=8 TeV
PHYSICAL REVIEW D 2015 DEC 1; 92(11):? Article 112001
The per-event yield of the highest transverse momentum charged particle and charged-particle jet, integrated above a given p(T)(min) threshold starting at p(T)(min) = 0.8 and 1 GeV, respectively, is studied in pp collisions at root s = 8 TeV. The particles and the jets are measured in the pseudorapidity ranges vertical bar n vertical bar < 2.4 and 1.9, respectively. The data are sensitive to the momentum scale at which parton densities saturate in the proton, to multiple partonic interactions, and to other key aspects of the transition between the soft and hard QCD regimes in hadronic collisions.
About F, Oudot-Mellakh T, Niay J, Rabiega P, Pedergnana V, Duffy D, Sultanik P, Cagnot C, Carrat F, Marcellin P, Zoulim F, Larrey D, Hezode C, Fontaine H, Bronowicki JP, Pol S, Albert ML, Theodorou I, Cobat A, Abel L
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Impact of IL28B, APOH and ITPA Polymorphisms on Efficacy and Safety of TVR- or BOC-Based Triple Therapy in Treatment-Experienced HCV-1 Patients with Compensated Cirrhosis from the ANRS CO20-CUPIC Study
PLOS ONE 2015 DEC 15; 10(12):? Article e0145105
Background Human genetic factors influence the outcome of pegylated interferon and ribavirin hepatitis C therapy. We explored the role of IL28B, APOH and ITPA SNPs on the outcomes of triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV-1. Patients and Methods A total of 256 HCV-1 Caucasian treatment-experienced patients with compensated cirrhosis from the ANRS CO20-CUPIC cohort were genotyped for a total of 10 candidate SNPs in IL28B (rs12979860 and rs368234815), APOH (rs8178822, rs12944940, rs10048158, rs52797880, rs1801689 and rs1801690) and ITPA (rs1127354 and rs7270101). We tested the association of IL28B and APOH SNPs with sustained virological response and of ITPA SNPs with anemia related phenotypes by means of logistic regression assuming an additive genetic model. Results None of the six APOH SNPs were associated with sustained virological response. The favorable alleles of the IL28B SNPs rs12979860 and rs368234815 were associated with sustained virological response (rs12979860: OR = 2.35[1.50-3.70], P = 2x10(-4)). Refined analysis showed that the effect of IL28B SNPs on sustained virological response was restricted to prior PegIFN/RBV relapse (OR = 3.80[1.82-8.92], P = 8x10(-4)). We also confirmed the association between ITPA low activity alleles and protection against early hemoglobin decline in triple therapy (P = 2x10(-5)). Conclusion Our results suggest that the screening of rs12979860 may remain interesting for decision making in prior relapse HCV-1 Caucasian patients with compensated cirrhosis eligible for a telaprevir-or boceprevir-based therapy.
Sun JC, Shi Y, Georgescu RE, Yuan ZN, Chait BT, Li HL, O'Donnell ME
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The architecture of a eukaryotic replisome
NATURE STRUCTURAL & MOLECULAR BIOLOGY 2015 DEC; 22(12):976-982
At the eukaryotic DNA replication fork, it is widely believed that the Cdc45-Mcm2-7-GINS (CMG) helicase is positioned in front to unwind DNA and that DNA polymerases trail behind the helicase. Here we used single-particle EM to directly image a Saccharomyces cerevisiae replisome. Contrary to expectations, the leading strand Pol epsilon is positioned ahead of CMG helicase, whereas Ctf4 and the lagging-strand polymerase (Pol) alpha-primase are behind the helicase. This unexpected architecture indicates that the leading-strand DNA travels a long distance before reaching Pol epsilon, first threading through the Mcm2-7 ring and then making a U-turn at the bottom and reaching Pol a at the top of CMG. Our work reveals an unexpected configuration of the eukaryotic replisome, suggests possible reasons for this architecture and provides a basis for further structural and biochemical replisome studies.
Kocabas A, Duarte T, Kumar S, Hynes MA
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Widespread Differential Expression of Coding Region and 3 ' UTR Sequences in Neurons and Other Tissues
NEURON 2015 DEC; 88(6):1149-1156
Mature messenger RNAs (mRNAs) consist of coding sequence (CDS) and 5' and 3' UTRs, typically expected to show similar abundance within a given neuron. Examining mRNA from defined neurons, we unexpectedly show extremely common unbalanced expression of cognate 3' UTR and CDS sequences; many genes show high 3' UTR relative to CDS, others show high CDS to 3' UTR. In situ hybridization (19 of 19 genes) shows a broad range of 3' UTR-to-CDS expression ratios across neurons and tissues. Ratios may be spatially graded or change with developmental age but are consistent across animals. Further, for two genes examined, a 3' UTR-to-CDS ratio above a particular threshold in any given neuron correlated with reduced or undetectable protein expression. Our findings raise questions about the role of isolated 3' UTR sequences in regulation of protein expression and highlight the importance of separately examining 3' UTR and CDS sequences in gene expression analyses.
Corregano L, Bastert K, da Rosa JC, Kost RG
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Accrual Index: A Real-Time Measure of the Timeliness of Clinical Study Enrollment
CTS-CLINICAL AND TRANSLATIONAL SCIENCE 2015 DEC; 8(6):655-661
BackgroundAchieving timely accrual into clinical research studies remains a challenge for clinical translational research. We developed an evaluation measure, the Accrual Index (AI), normalized for sample size and study duration, using data from the protocol and study management databases. We applied the AI retrospectively and prospectively to assess its utility. MethodsAccrual Target, Projected Time to Accrual Completion (PTAC), Evaluable Subjects, Dates of Recruitment Initiation, Analysis, and Completion were defined. AI is (% Accrual Target accrued/% PTAC elapsed). Changes to recruitment practices were described, and data extracted from study management databases. ResultsDecember 2014 (or final) AI was analyzed for 101 studies initiating recruitment from 2007 to 2014. Median AI was 1 for protocols initiating recruitment in 2011, 2013, and 2014. The AI varied widely for studies pre-2013. Studies with AI > 4 utilized convenience samples for recruitment. Data-justified PTAC was refined in 2013-2014 after which the AI range narrowed. Protocol characteristics were not associated with study AI. ConclusionProtocol AI reflects the relative agreement between accrual feasibility assessment (PTAC), and accrual performance, and is affected by recruitment practices. The AI may be useful in managing accountability, modeling accrual, allocating recruitment resources, and testing innovations in recruitment practices.
Lee KW, Westin L, Kim J, Chang JC, Oh YS, Amreen B, Gresack J, Flajolet M, Kim D, Aperia A, Kim Y, Greengard P
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Alteration by p11 of mGluR5 localization regulates depression-like behaviors
MOLECULAR PSYCHIATRY 2015 DEC; 20(12):1546-1556
Mood disorders and antidepressant therapy involve alterations of monoaminergic and glutamatergic transmission. The protein S100A10 (p11) was identified as a regulator of serotonin receptors, and it has been implicated in the etiology of depression and in mediating the antidepressant actions of selective serotonin reuptake inhibitors. Here we report that p11 can also regulate depression-like behaviors via regulation of a glutamatergic receptor in mice. p11 directly binds to the cytoplasmic tail of metabotropic glutamate receptor 5 (mGluR5). p11 and mGluR5 mutually facilitate their accumulation at the plasma membrane, and p11 increases cell surface availability of the receptor. Whereas p11 overexpression potentiates mGluR5 agonist-induced calcium responses, overexpression of mGluR5 mutant, which does not interact with p11, diminishes the calcium responses in cultured cells. Knockout of mGluR5 or p11 specifically in glutamatergic neurons in mice causes depression-like behaviors. Conversely, knockout of mGluR5 or p11 in GABAergic neurons causes antidepressant-like behaviors. Inhibition of mGluR5 with an antagonist, 2-methyl-6-(phenylethynyl) pyridine (MPEP), induces antidepressant-like behaviors in a p11-dependent manner. Notably, the antidepressant-like action of MPEP is mediated by parvalbumin-positive GABAergic interneurons, resulting in a decrease of inhibitory neuronal firing with a resultant increase of excitatory neuronal firing. These results identify a molecular and cellular basis by which mGluR5 antagonism achieves its antidepressant-like activity.
Yao X, Tang ZY, Fu X, Yin JW, Liang Y, Li CH, Li HY, Tian Q, Roeder RG, Wang G
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The Mediator subunit MED23 couples H2B mono-ubiquitination to transcriptional control and cell fate determination
EMBO JOURNAL 2015 DEC 2; 34(23):2885-2902
The Mediator complex orchestrates multiple transcription factors with the Pol II apparatus for precise transcriptional control. However, its interplay with the surrounding chromatin remains poorly understood. Here, we analyze differential histone modifications between WT and MED23(-/-) (KO) cells and identify H2B mono-ubiquitination at lysine 120 (H2Bub) as a MED23-dependent histone modification. Using tandem affinity purification and mass spectrometry, we find that MED23 associates with the RNF20/40 complex, the enzyme for H2Bub, and show that this association is critical for the recruitment of RNF20/40 to chromatin. In a cell-free system, Mediator directly and substantially increases H2Bub on recombinant chromatin through its cooperation with RNF20/40 and the PAF complex. Integrative genome-wide analyses show that MED23 depletion specifically reduces H2Bub on a subset of MED23-controlled genes. Importantly, MED23-coupled H2Bub levels are oppositely regulated during myogenesis and lung carcinogenesis. In sum, these results establish a mechanistic link between the Mediator complex and a critical chromatin modification in coordinating transcription with cell growth and differentiation.
Wang Q, Euler CW, Delaune A, Fischetti VA
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Using a Novel Lysin To Help Control Clostridium difficile Infections
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 2015 DEC; 59(12):7447-7457
As a consequence of excessive antibiotic therapies in hospitalized patients, Clostridium difficile, a Gram-positive anaerobic spore-forming intestinal pathogen, is the leading cause of hospital-acquired diarrhea and colitis. Drug treatments for these diseases are often complicated by antibiotic-resistant strains and a high frequency of treatment failures and relapse; therefore, novel nonantibiotic approaches may prove to be more effective. In this study, we recombinantly expressed a prophage lysin identified from a C. difficile strain, CD630, which we named PlyCD. PlyCD was found to have lytic activity against specific C. difficile strains. However, the recombinantly expressed catalytic domain of this protein, PlyCD(1-174), displayed significantly greater lytic activity (>4-log kill) and a broader lytic spectrum against C. difficile strains while still retaining a high degree of specificity toward C. difficile versus commensal clostridia and other bacterial species. Our data also indicated that noneffective doses of vancomycin and PlyCD(1-174) when combined in vitro could be significantly more bactericidal against C. difficile. In an ex vivo treatment model of mouse colon infection, we found that PlyCD(1-174) functioned in the presence of intestinal contents, significantly decreasing colonizing C. difficile compared to controls. Together, these data suggest that PlyCD(1-174) has potential as a novel therapeutic for clinical application against C. difficile infection, either alone or in combination with other preexisting treatments to improve their efficacy.