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Found 37769 matches. Displaying 5731-5740
Freund NT, Horwitz JA, Nogueira L, Sievers SA, Scharf L, Scheid JF, Gazumyan A, Liu C, Velinzon K, Goldenthal A, Sanders RW, Moore JP, Bjorkman PJ, Seaman MS, Walker BD, Klein F, Nussenzweig MC
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A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo
PLoS Pathogens 2015 OCT; 11(10):? Article e1005238
The CD4 binding site (CD4bs) on the envelope glycoprotein is a major site of vulnerability that is conserved among different HIV-1 isolates. Many broadly neutralizing antibodies (bNAbs) to the CD4bs belong to the VRC01 class, sharing highly restricted origins, recognition mechanisms and viral escape pathways. We sought to isolate new anti-CD4bs bNAbs with different origins and mechanisms of action. Using a gp120 2CC core as bait, we isolated antibodies encoded by IGVH3-21 and IGVL3-1 genes with long CDRH3s that depend on the presence of the N-linked glycan at position-276 for activity. This binding mode is similar to the previously identified antibody HJ16, however the new antibodies identified herein are more potent and broad. The most potent variant, 179NC75, had a geometric mean IC80 value of 0.42 mu g/ml against 120 Tier-2 HIV-1 pseudoviruses in the TZM.bl assay. Although this group of CD4bs glycan-dependent antibodies can be broadly and potently neutralizing in vitro, their in vivo activity has not been tested to date. Here, we report that 179NC75 is highly active when administered to HIV-1-infected humanized mice, where it selects for escape variants that lack a glycan site at position-276. The same glycan was absent from the virus isolated from the 179NC75 donor, implying that the antibody also exerts selection pressure in humans.
Capel F, Chabrier G, Pitois E, Rigaudiere JP, Le Plenier S, Durand C, Jouve C, de Bandt JP, Cynober L, Moinard C, Morio B
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Combining citrulline with atorvastatin preserves glucose homeostasis in a murine model of diet-induced obesity
BRITISH JOURNAL OF PHARMACOLOGY 2015 OCT; 172(20):4996-5008
Background and PurposeNO is a crucial regulator of energy and lipid metabolism, whose homeostasis is compromised during obesity. Combination of citrulline and atorvastatin potentiated NO production in vitro. Here we have assessed the effects of this combination in mice with diet-induced obesity (DIO). Experimental ApproachC57BL/6J male mice were given a standard diet (control) or a high fat-high sucrose diet (DIO) for 8 weeks. DIO mice were then treated with DIO alone, DIO with citrulline, DIO with atorvastatin or DIO with citrulline and atorvastatin (DIOcit-stat) for 3 weeks. Thereafter, body composition, glucose tolerance, insulin sensitivity and liver fat metabolism were measured. Key ResultsDIOcit-stat mice showed lower body weight, fat mass and epididymal fat depots compared with other DIO groups. Unlike other DIO groups, glucose tolerance and insulin sensitivity of DIOcit-stat, along with blood glucose and insulin concentrations in response to feeding, were restored to control values. Refeeding-induced changes in liver lipogenic activity were also reduced in DIOcit-stat mice compared with those of DIO animals. This was associated with decreased gene expression of the transcription factor SREBP-1, liver X receptor , ChREBP and of target lipogenic enzymes in the liver of DIOcit-stat mice compared with those of other DIO groups. Conclusions and ImplicationsThe citrulline-atorvastatin combination prevented fat mass accumulation and maintained glucose homeostasis in DIO mice. Furthermore, it potentiated inhibition of hepatic de novo lipogenesis activity. This combination has potential for preservation of glucose homeostasis in patients receiving statin therapy.
Perez-Garijo A, Steller H
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Spreading the word: non-autonomous effects of apoptosis during development, regeneration and disease
DEVELOPMENT 2015 OCT 1; 142(19):3253-3262
Apoptosis, in contrast to other forms of cell death such as necrosis, was originally regarded as a 'silent' mechanism of cell elimination designed to degrade the contents of doomed cells. However, during the past decade it has become clear that apoptotic cells can produce diverse signals that have a profound impact on neighboring cells and tissues. For example, apoptotic cells can release factors that influence the proliferation and survival of adjacent tissues. Apoptosis can also affect tissue movement and morphogenesis by modifying tissue tension in surrounding cells. As we review here, these findings reveal unexpected roles for apoptosis in tissue remodeling during development, as well as in regeneration and cancer.
Roberts WK, Blachere NE, Frank MO, Dousmanis A, Ransohoff RM, Darnell RB
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A Destructive Feedback Loop Mediated by CXCL10 in Central Nervous System Inflammatory Disease
ANNALS OF NEUROLOGY 2015 OCT; 78(4):619-629
Objective: Paraneoplastic neurologic disorders (PND) are autoimmune diseases associated with cancer and ectopic expression of a neuronal antigen in a peripheral tumor. Patients with PND harbor high-titer antibodies and T cells in their serum and cerebrospinal fluid (CSF) that are specific to the tumor antigen, and treatment with the immunosuppressant FK506 (tacrolimus) decreases CSF white blood cell counts. The objective of this study was to determine the effect of FK506 on CSF chemokine levels in PND patients. Methods: CSF samples before and after FK506 treatment were tested by multiplex assay for the presence of 27 cytokines. Follow-up in vitro experiments aimed to determine whether T cells secrete CXCL10 in response to cognate antigen. Results: Here we report that PND patients harbor high levels of the chemokine CXCL10 in their CSF. CXCL10 is a cytokine that recruits CXCR3(+) cells such as activated T cells, and we found that FK506 treatment specifically decreased CSF CXCL10 from among 27 cytokines tested. In vitro, CXCL10 was only produced during antigen-specific cognate interactions between T cells and antigen-presenting cells (APCs) when interferon-gamma (IFN gamma) receptors were present on the T cell. Interpretation: These results support a model in which antigen-specific T cell stimulation by PND APCs triggers IFN gamma, followed by CXCL10 production and further lymphocyte recruitment, suggesting that treatments targeting T cells or CXCL10 in the central nervous system (CNS) may interrupt a destructive positive feedback loop present in CNS inflammation.
Wang H, Niu QW, Wu HW, Liu J, Ye J, Yu N, Chua NH
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Analysis of non-coding transcriptome in rice and maize uncovers roles of conserved lncRNAs associated with agriculture traits
PLANT JOURNAL 2015 OCT; 84(2):404-416
Long non-coding RNAs (lncRNAs) have recently been found to widely exist in eukaryotes and play important roles in key biological processes. To extend our knowledge of lncRNAs in crop plants we performed both non-directional and strand-specific RNA-sequencing experiments to profile non-coding transcriptomes of various rice and maize organs at different developmental stages. Analysis of more than 3 billion reads identified 22334 long intergenic non-coding RNAs (lincRNAs) and 6673 pairs of sense and natural antisense transcript (NAT). Many lincRNA genes were associated with epigenetic marks. Expression of rice lincRNA genes was significantly correlated with that of nearby protein-coding genes. A set of NAT genes also showed expression correlation with their sense genes. More than 200 rice lincRNA genes had homologous non-coding sequences in the maize genome. Much more lincRNA and NAT genes were derived from conserved genomic regions between the two cereals presenting positional conservation. Protein-coding genes flanking or having a sense-antisense relationship to these conserved lncRNA genes were mainly involved in development and stress responses, suggesting that the associated lncRNAs might have similar functions. Integrating previous genome-wide association studies (GWAS), we found that hundreds of lincRNAs contain trait-associated SNPs (single nucleotide polymorphisms [SNPs]) suggesting their putative contributions to developmental and agriculture traits. Significance Statement Long noncoding RNAs (lncRNAs) play key roles in numerous biological processes. Here we sequenced and characterized lncRNAs from many rice and maize tissues.Hundreds of the lncRNAs have single nucleotide polymorphisms associated with agricultural traits, suggesting that they may play roles in controlling such traits.
Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, Brandstetter J, Brondolin E, Dragicevic M, Ero J, Flechl M, Friedl M, Fruhwirth R, Ghete VM, Hartl C, Hormann N, Hrubec J, Jeitler M, Knunz V, Konig A, Krammer M, Kratschmer I, Liko D, Matsushita T, Mikulec I, Rabady D, Rahbaran B, Rohringer H, Schieck J, Schofbeck R, Strauss J, Treberer-Treberspurg W, Waltenberger W, Wulz CE, Mossolov V, Shumeiko N, Gonzalez JS, Alderweireldt S, Cornelis T, De Wolf EA, Janssen X, Knutsson A, Lauwers J, Luyckx S, Ochesanu S, Rougny R, Van De Klundert M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Van Spilbeeck A, Abu Zeid S, Blekman F, D'Hondt J, Daci N, De Bruyn I, Deroover K, Heracleous N, Keaveney J, Lowette S, Moreels L, Olbrechts A, Python Q, Strom D, Tavernier S, Van Doninck W, Van Mulders P, Van Onsem GP, Van Parijs I, Barria P, Caillol C, Clerbaux B, De Lentdecker G, Delannoy H, Fasanella G, Favart L, Gay APR, Grebenyuk A, Lenzi T, Leonard A, Maerschalk T, Marinov A, Pernie L, Randle-conde A, Reis T, Seva T, Vander Velde C, Vanlaer P, Yonamine R, Zenoni F, Zhang F, Beernaert K, Benucci L, Cimmino A, Crucy S, Dobur D, Fagot A, Garcia G, Gul M, Mccartin J, Rios AAO, Poyraz D, Ryckbosch D, Salva S, Sigamani M, Strobbe N, Tytgat M, Van Driessche W, Yazgan E, Zaganidis N, Basegmez S, Beluffi C, Bondu O, Brochet S, Bruno G, Castello R, Caudron A, Ceard L, Da Silveira GG, Delaere C, Favart D, Forthomme L, Giammanco A, Hollar J, Jafari A, Jez P, Komm M, Lemaitre V, Mertens A, Nuttens C, Perrini L, Pin A, Piotrzkowski K, Popov A, Quertenmont L, Selvaggi M, Marono MV, Beliy N, Hammad GH, Alda WL, Alves GA, Brito L, Martins MC, Hamer M, Hensel C, Herrera CM, Moraes A, Pol ME, Teles PR, Das Chagas EBB, Carvalho W, Chinellato J, Custodio A, Da Costa EM, Damiao DDJ, Martins CDO, De Souza SF, Guativa LMH, Malbouisson H, Figueiredo DM, Mundim L, Nogima H, Da Silva WLP, Santoro A, Sznajder A, Manganote EJT, Pereira AV, Ahuja S, Bernardes CA, Santos ADS, Dogra S, Tomei TRFP, Gregores EM, Mercadante PG, Moon CS, Novaes SF, Padula SS, Abad DR, Vargas JCR, Aleksandrov A, Genchev V, Hadjiiska R, Iaydjiev P, Piperov S, Rodozov M, Stoykova S, Sultanov G, Vutova M, Dimitrov A, Glushkov I, Litov L, Pavlov B, Petkov P, Ahmad M, Bian JG, Chen GM, Chen HS, Chen M, Cheng T, Du R, Jiang CH, Plestina R, Romeo F, Shaheen SM, Tao J, Wang C, Wang Z, Zhang H, Zou W, Ban Y, Li Q, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Zou W, Avila C, Cabrera A, Sierra LFC, Florez C, Gomez JP, Moreno BG, Sanabria JC, Godinovic N, Lelas D, Polic D, Puljak I, Cipriano PMR, Antunovic Z, Kovac M, Brigljevic V, Kadija K, Luetic J, Micanovic S, Sudic L, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Bodlak M, Finger M, Finger M, El-khateeb E, Elkafrawy T, Mohamed A, Salama E, Calpas B, Kadastik M, Murumaa M, Raidal M, Tiko A, Veelken C, Eerola P, Pekkanen J, Voutilainen M, Harkonen J, Karimaki V, Kinnunen R, Lampen T, Lassila-Perini K, Lehti S, Linden T, Luukka P, Maenpaa T, Peltola T, Tuominen E, Tuominiemi J, Tuovinen E, Wendland L, Talvitie J, Tuuva T, Besancon M, Couderc F, Dejardin M, Denegri D, Fabbro B, Faure JL, Favaro C, Ferri F, Ganjour S, Givernaud A, Gras P, de Monchenault GH, Jarry P, Locci E, Machet M, Malcles J, Rander J, Rosowsky A, Titov M, Zghiche A, Antropov I, Baffioni S, Beaudette F, Busson P, Cadamuro L, Chapon E, Charlot C, Dahms T, Davignon O, Filipovic N, Florent A, de Cassagnac RG, Lisniak S, Mastrolorenzo L, Mine P, Naranjo IN, Nguyen M, Ochando C, Ortona G, Paganini P, Regnard S, Salerno R, Sauvan JB, Sirois Y, Strebler T, Yilmaz Y, Zabi A, Agram JL, Andrea J, Aubin A, Bloch D, Brom JM, Buttignol M, Chabert EC, Chanon N, Collard C, Conte E, Coubez X, Fontaine JC, Gele D, Goerlach U, Goetzmann C, Le Bihan AC, Merlin JA, Skovpen K, Van Hove P, Gadrat S, Beauceron S, Bernet C, Boudoul G, Bouvier E, Montoya CAC, Chasserat J, Chierici R, Contardo D, Courbon B, Depasse P, El Mamouni H, Fan J, Fay J, Gascon S, Gouzevitch M, Ille B, Lagarde F, Laktineh IB, Lethuillier M, Mirabito L, Pequegnot AL, Perries S, Alvarez JDR, Sabes D, Sgandurra L, Sordini V, Vander Donckt M, Verdier P, Viret S, Xiao H, Toriashvili T, Tsamalaidze Z, Autermann C, Beranek S, Edelhoff M, Feld L, Heister A, Kiesel MK, Klein K, Lipinski M, Ostapchuk A, Preuten M, Raupach F, Schael S, Schulte JF, Verlage T, Weber H, Wittmer B, Zhukov V, Ata M, Brodski M, Dietz-Laursonn E, Duchardt D, Endres M, Erdmann M, Erdweg S, Esch T, Fischer R, Guth A, Hebbeker T, Heidemann C, Hoepfner K, Klingebiel D, Knutzen S, Kreuzer P, Merschmeyer M, Meyer A, Millet P, Olschewski M, Padeken K, Papacz P, Pook T, Radziej M, Reithler H, Rieger M, Scheuch F, Sonnenschein L, Teyssier D, Thuer S, Cherepanov V, Erdogan Y, Flugge G, Geenen H, Geisler M, Hoehle F, Kargoll B, Kress T, Kuessel Y, Kunsken A, Lingemann J, Nehrkorn A, Nowack A, Nugent IM, Pistone C, Pooth O, Stahl A, Martin MA, Asin I, Bartosik N, Behnke O, Behrens U, Bell AJ, Borras K, Burgmeier A, Cakir A, Calligaris L, Campbell A, Choudhury S, Costanza F, Pardos CD, Dolinska G, Dooling S, Dorland T, Eckerlin G, Eckstein D, Eichhorn T, Flucke G, Gallo E, Garcia JG, Geiser A, Gizhko A, Gunnellini P, Hauk J, Hempel M, Jung H, Kalogeropoulos A, Karacheban O, Kasemann M, Katsas P, Kieseler J, Kleinwort C, Korol I, Lange W, Leonard J, Lipka K, Lobanov A, Lohmann W, Mankel R, Marfin I, Melzer-Pellmann IA, Meyer AB, Mittag G, Mnich J, Mussgiller A, Naumann-Emme S, Nayak A, Ntomari E, Perrey H, Pitzl D, Placakyte R, Raspereza A, Roland B, Sahin MO, Saxena P, Schoerner-Sadenius T, Schroder M, Seitz C, Spannagel S, Trippkewitz KD, Walsh R, Wissing C, Blobel V, Vignali MC, Draeger AR, Erfle J, Garutti E, Goebel K, Gonzalez D, Gorner M, Haller J, Hoffmann M, Hoing RS, Junkes A, Klanner R, Kogler R, Lapsien T, Lenz T, Marchesini I, Marconi D, Nowatschin D, Ott J, Pantaleo F, Peiffer T, Perieanu A, Pietsch N, Poehlsen J, Rathjens D, Sander C, Schettler H, Schleper P, Schlieckau E, Schmidt A, Schwandt J, Seidel M, Sola V, Stadie H, Steinbruck G, Tholen H, Troendle D, Usai E, Vanelderen L, Vanhoefer A, Akbiyik M, Barth C, Baus C, Berger J, Boser C, Butz E, Chwalek T, Colombo F, De Boer W, Descroix A, Dierlamm A, Fink S, Frensch F, Giffels M, Gilbert A, Hartmann F, Heindl SM, Husemann U, Katkov I, Kornmayer A, Pardo PL, Maier B, Mildner H, Mozer MU, Muller T, Muller T, Plagge M, Quast G, Rabbertz K, Rocker S, Roscher F, Simonis HJ, Stober FM, Ulrich R, Wagner-Kuhr J, Wayand S, Weber M, Weiler T, Wohrmann C, Wolf R, Anagnostou G, Daskalakis G, Geralis T, Giakoumopoulou VA, Kyriakis A, Loukas D, Psallidas A, Topsis-Giotis I, Agapitos A, Kesisoglou S, Panagiotou A, Saoulidou N, Tziaferi E, Evangelou I, Flouris G, Foudas C, Kokkas P, Loukas N, Manthos N, Papadopoulos I, Paradas E, Strologas J, Bencze G, Hajdu C, Hazi A, Hidas P, Horvath D, Sikler F, Veszpremi V, Vesztergombi G, Zsigmond AJ, Beni N, Czellar S, Karancsi J, Molnar J, Szillasi Z, Bartok M, Makovec A, Raics P, Trocsanyi ZL, Ujvari B, Mal P, Mandal K, Sahoo N, Swain SK, Bansal S, Beri SB, Bhatnagar V, Chawla R, Gupta R, Bhawandeep U, Kalsi AK, Kaur A, Kaur M, Kumar R, Mehta A, Mittal M, Singh JB, Walia G, Kumar A, Kumar A, Bhardwaj A, Choudhary BC, Garg RB, Kumar A, Malhotra S, Naimuddin M, Nishu N, Ranjan K, Sharma R, Sharma V, Banerjee S, Bhattacharya S, Chatterjee K, Dey S, Dutta S, Jain S, Majumdar N, Modak A, Mondal K, Mukherjee S, Mukhopadhyay S, Roy A, Roy D, Chowdhury SR, Sarkar S, Sharan M, Abdulsalam A, Chudasama R, Dutta D, Jha V, Kumar V, Mohanty AK, Pant LM, Shukla P, Topkar A, Aziz T, Banerjee S, Bhowmik S, Chatterjee RM, Dewanjee RK, Dugad S, Ganguly S, Ghosh S, Guchait M, Gurtu A, Kole G, Kumar S, Mahakud B, Maity M, Majumder G, Mazumdar K, Mitra S, Mohanty GB, Parida B, Sarkar T, Sudhakar K, Sur N, Sutar B, Wickramage N, Chauhan S, Dube S, Sharma S, Bakhshiansohi H, Behnamian H, Etesami SM, Fahim A, Goldouzian R, Khakzad M, Najafabadi MM, Naseri M, Mehdiabadi SP, Hosseinabadi FR, Safarzadeh B, Zeinali M, Felcini M, Grunewald M, Abbrescia M, Calabria C, Caputo C, Chhibra SS, Colaleo A, Creanza D, Cristella L, De Filippis N, De Palma M, Fiore L, Iaselli G, Maggi G, Maggi M, Miniello G, My S, Nuzzo S, Pompili A, Pugliese G, Radogna R, Ranieri A, Selvaggi G, Silvestris L, Venditti R, Verwilligen P, Abbiendi G, Battilana C, Benvenuti AC, Bonacorsi D, Braibant-Giacomelli S, Brigliadori L, Campanini R, Capiluppi P, Castro A, Cavallo FR, Codispoti G, Cuffiani M, Dallavalle GM, Fabbri F, Fanfani A, Fasanella D, Giacomelli P, Grandi C, Guiducci L, Marcellini S, Masetti G, Montanari A, Navarria FL, Perrotta A, Rossi AM, Rovelli T, Siroli GP, Tosi N, Travaglini R, Cappello G, Chiorboli M, Costa S, Giordano F, Potenza R, Tricomi A, Tuve C, Barbagli G, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Gonzi S, Gori V, Lenzi P, Meschini M, Paoletti S, Sguazzoni G, Tropiano A, Viliani L, Benussi L, Bianco S, Fabbri F, Piccolo D, Calvelli V, Ferro F, Lo Vetere M, Monge MR, Robutti E, Tosi S, Brianza L, Dinardo ME, Fiorendi S, Gennai S, Gerosa R, Ghezzi A, Govoni P, Malvezzi S, Manzoni RA, Marzocchi B, Menasce D, Moroni L, Paganoni M, Pedrini D, Ragazzi S, Redaelli N, de Fatis TT, Buontempo S, Cavallo N, Di Guida S, Esposito M, Fabozzi F, Iorio AOM, Lanza G, Lista L, Meola S, Merola M, Paolucci P, Sciacca C, Thyssen F, Azzi P, Bacchetta N, Benato L, Bisello D, Boletti A, Branca A, Carlin R, De Oliveira ACA, Checchia P, Dall'Osso M, Dorigo T, Dosselli U, Gasparini F, Gasparini U, Gozzelino A, Kanishchev K, Lacaprara S, Margoni M, Meneguzzo AT, Pazzini J, Pozzobon N, Ronchese P, Simonetto F, Torassa E, Tosi M, Zanetti M, Zotto P, Zucchetta A, Zumerle G, Braghieri A, Magnani A, Montagna P, Ratti SP, Re V, Riccardi C, Salvini P, Vai I, Vitulo P, Solestizi LA, Biasini M, Bilei GM, Ciangottini D, Fano L, Lariccia P, Mantovani G, Menichelli M, Saha A, Santocchia A, Spiezia A, Androsov K, Azzurri P, Bagliesi G, Bernardini J, Boccali T, Broccolo G, Castaldi R, Ciocci MA, Dell'Orso R, Donato S, Fedi G, Foa L, Giassi A, Grippo MT, Ligabue F, Lomtadze T, Martini L, Messineo A, Palla F, Rizzi A, Savoy-Navarro A, Serban AT, Spagnolo P, Squillacioti P, Tenchini R, Tonelli G, Venturi A, Verdini PG, Barone L, Cavallari F, D'imperio G, Del Re D, Diemoz M, Gelli S, Jorda C, Longo E, Margaroli F, Meridiani P, Micheli F, Organtini G, Paramatti R, Preiato F, Rahatlou S, Rovelli C, Santanastasio F, Traczyk P, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Bellan R, Biino C, Cartiglia N, Costa M, Covarelli R, Degano A, Demaria N, Finco L, Kiani B, Mariotti C, Maselli S, Migliore E, Monaco V, Monteil E, Musich M, Obertino MM, Pacher L, Pastrone N, Pelliccioni M, Angioni GLP, Ravera F, Romero A, Ruspa M, Sacchi R, Solano A, Staiano A, Tamponi U, Belforte S, Candelise V, Casarsa M, Cossutti F, Della Ricca G, Gobbo B, La Licata C, Marone M, Schizzi A, Umer T, Zanetti A, Chang S, Kropivnitskaya A, Nam SK, Kim DH, Kim GN, Kim MS, Kong DJ, Lee S, Oh YD, Sakharov A, Son DC, Cifuentes JAB, Kim H, Kim TJ, Ryu MS, Song S, Choi S, Go Y, Gyun D, Hong B, Jo M, Kim H, Kim Y, Lee B, Lee K, Lee KS, Lee S, Park SK, Roh Y, Yoo HD, Choi M, Kim H, Kim JH, Lee JSH, Park IC, Ryu G, Choi Y, Choi YK, Goh J, Kim D, Kwon E, Lee J, Yu I, Juodagalvis A, Vaitkus J, Ahmed I, Ibrahim ZA, Komaragiri JR, Ali MABM, Idris FM, Abdullah WATW, Yusli MN, Linares EC, Castilla-Valdez H, De La Cruz-Burelo E, Heredia-De La Cruz I, Hernandez-Almada A, Lopez-Fernandez R, Sanchez-Hernandez A, Moreno SC, Valencia FV, Carpinteyro S, Pedraza I, Ibarguen HAS, Pineda AM, Krofcheck D, Butler PH, Reucroft S, Ahmad A, Ahmad M, Hassan Q, Hoorani HR, Khan WA, Khurshid T, Shoaib M, Bialkowska H, Bluj M, Boimska B, Frueboes T, Gorski M, Kazana M, Nawrocki K, Romanowska-Rybinska K, Szleper M, Zalewski P, Brona G, Bunkowski K, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Olszewski M, Walczak M, Bargassa P, Silva CBDE, Di Francesco A, Faccioli P, Parracho 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Limits on the Higgs boson lifetime and width from its decay to four charged leptons
PHYSICAL REVIEW D 2015 OCT 22; 92(7):? Article 072010
Constraints on the lifetime and width of the Higgs boson are obtained from H -> ZZ -> 4l events using data recorded by the CMS experiment during the LHC run 1 with an integrated luminosity of 5.1 and 19.7 fb(-1) at a center-of-mass energy of 7 and 8 TeV, respectively. The measurement of the Higgs boson lifetime is derived from its flight distance in the CMS detector with an upper bound of tau(H) < 1.9 x 10(-13) s at the 95% confidence level (C.L.), corresponding to a lower bound on the width of Gamma(H) > 3.5 x 10(-9) MeV. The measurement of the width is obtained from an off-shell production technique, generalized to include anomalous couplings of the Higgs boson to two electroweak bosons. From this measurement, a joint constraint is set on the Higgs boson width and a parameter f(Lambda Q) that expresses an anomalous coupling contribution as an on-shell cross-section fraction. The limit on the Higgs boson width is Gamma(H) < 46 MeV with f(Lambda Q) unconstrained and Gamma(H) < 26 MeV for f(Lambda Q) = 0 at the 95% C.L. The constraint f(Lambda Q) < 3.8 x 10(-3) at the 95% C.L. is obtained for the expected standard model Higgs boson width.
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Ecklund KM, 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, Khukhunaishvili A, Korjenevski S, Petrillo G, 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, Patel R, 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, Eusebi R, Flanagan W, Gilmore J, Kamon T, Khotilovich V, Krutelyov V, Montalvo R, Osipenkov I, Pakhotin Y, 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, 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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Measurements of the ZZ production cross sections in the 2l2 nu channel in proton-proton collisions at root s=7 and 8 TeV and combined constraints on triple gauge couplings
EUROPEAN PHYSICAL JOURNAL C 2015 OCT 29; 75(10):? Article 511
Measurements of the ZZ production cross sections in proton-proton collisions at center-of-mass energies of 7 and 8 TeV are presented. Candidate events for the leptonic decay mode ZZ -> 2l2 nu. where l denotes an electron or a muon, are reconstructed and selected from data corresponding to an integrated luminosity of 5.1 (19.6) fb(-1) at 7 (8) TeV collected with the CMS experiment. The measured cross sections, sigma(pp -> ZZ) = 5.1(1.4)(+1.5) (stat)(-1.1)(+1.4) (syst) +/- 0.1 (lumi) pb at 7 TeV, and 7.2(-0.8)(+0.8) (stat)(1.5)(+1.9) (syst) +/- 0.2 (lumi) pb at 8 TeV, are in good agreement with the standard model predictions with next-to-leading-order accuracy. The selected data are analyzed to search for anomalous triple gauge couplings involving the ZZ final state. In the absence of any deviation from the standard model predictions, limits are set on the relevant parameters. These limits are then combined with the previously published CMS results for ZZ in 4l final states, yielding the most stringent constraints on the anomalous couplings.
Sun HS, Damez-Werno DM, Scobie KN, Shao NY, Dias C, Rabkin J, Koo JW, Korb E, Bagot RC, Ahn FH, Cahill ME, Labonte B, Mouzon E, Heller EA, Cates H, Golden SA, Gleason K, Russo SJ, Andrews S, Neve R, Kennedy PJ, Maze I, Dietz DM, Allis CD, Turecki G, Varga-Weisz P, Tamminga C, Shen L, Nestler EJ
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ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior
NATURE MEDICINE 2015 OCT; 21(10):1146-1153
Improved treatment for major depressive disorder (MDD) remains elusive because of the limited understanding of its underlying biological mechanisms. It is likely that stress-induced maladaptive transcriptional regulation in limbic neural circuits contributes to the development of MDD, possibly through epigenetic factors that regulate chromatin structure. We establish that persistent upregulation of the ACF (ATP-utilizing chromatin assembly and remodeling factor) ATP-dependent chromatin-remodeling complex, occurring in the nucleus accumbens of stress-susceptible mice and depressed humans, is necessary for stress-induced depressive-like behaviors. We found that altered ACF binding after chronic stress was correlated with altered nucleosome positioning, particularly around the transcription start sites of affected genes. These alterations in ACF binding and nucleosome positioning were associated with repressed expression of genes implicated in susceptibility to stress. Together, our findings identify the ACF chromatin-remodeling complex as a critical component in the development of susceptibility to depression and in regulating stress-related behaviors.
Nankya IL, Tebit DM, Abraha A, Kyeyune F, Gibson R, Jegede O, Nickel G, Arts EJ
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Defining the fitness of HIV-1 isolates with dual/mixed co-receptor usage
AIDS RESEARCH AND THERAPY 2015 OCT 3; 12(?):? Article 34
Background: CCR5-using (r5) HIV-1 predominates during asymptomatic disease followed by occasional emergence of CXCR4-using (x4) or dual tropic (r5x4) virus. We examined the contribution of the x4 and r5 components to replicative fitness of HIV-1 isolates. Methods: Dual tropic r5x4 viruses were predicted from average HIV-1 env sequences of two primary subtype C HIV-1 isolates (C19 and C27) and from two patient plasma samples (B12 and B19). Chimeric Env viruses with an NL4-3 backbone were constructed from the B12 and B19 env sequences. To determine replicative fitness, these primary and chimeric dual tropic HIV-1 were then competed against HIV-1 reference isolates in U87. CD4 cells expressing CXCR4 or CCR5 or in PBMCs +/- entry inhibitors. Contribution of the x4 and r5 clones within the quasispecies of these chimeric or primary HIV-1 isolates were then compared to the frequency of x4, r5, and dual tropic clones within the quasispecies as predicted by phenotypic assays, clonal sequencing, and 454 deep sequencing. Results: In the primary HIV-1 isolates (C19 and C27), subtype C dual tropic clones dominated over x4 clones while pure r5 clones were absent. In two subtype B chimeric viruses (B12 and B19), r5 clones were > 100-fold more abundant than x4 or r5/x4 clones. The dual tropic C19 and C27 HIV-1 isolates outcompeted r5 primary HIV-1 isolates, B2 and C3 in PBMCs. When AMD3100 was added or when only U87. CD4. CCR5 cells were used, the B2 and C3 reference viruses now out-competed the r5 component of the dual tropic C19 and C27. In contrast, the same replicative fitness was observed with dualtropic B12 and B19 HIV-1 isolates relative to x4 HIV-1 A8 and E6 or the r5 B2 and C3 viruses, even when the r5 or x4 component was inhibited by maraviroc (or AMD3100) or in U87. CD4. CXCR4 (or CCR5) cells. Conclusions: In the dual tropic HIV-1 isolates, the x4 replicative fitness is higher than r5 clones but the x4 or x4/r5 clones are typically at low frequency in the intrapatient virus population. Ex vivo HIV propagation promotes outgrowth of the x4 clones and provides an over-estimate of x4 dominance in replicative fitness within dual tropic viruses.
Dar RD, Razooky BS, Weinberger LS, Cox CD, Simpson ML
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The Low Noise Limit in Gene Expression
PLOS ONE 2015 OCT 21; 10(10):? Article e0140969
Protein noise measurements are increasingly used to elucidate biophysical parameters. Unfortunately noise analyses are often at odds with directly measured parameters. Here we show that these inconsistencies arise from two problematic analytical choices: (i) the assumption that protein translation rate is invariant for different proteins of different abundances, which has inadvertently led to (ii) the assumption that a large constitutive extrinsic noise sets the low noise limit in gene expression. While growing evidence suggests that transcriptional bursting may set the low noise limit, variability in translational bursting has been largely ignored. We show that genome-wide systematic variation in translational efficiency can-and in the case of E. coli does-control the low noise limit in gene expression. Therefore constitutive extrinsic noise is small and only plays a role in the absence of a systematic variation in translational efficiency. These results show the existence of two distinct expression noise patterns: (1) a global noise floor uniformly imposed on all genes by expression bursting; and (2) high noise distributed to only a select group of genes.