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Charpentier E, Marraffini LA
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Editorial overview: Novel technologies in microbiology: Recent advances in techniques in microbiology
CURRENT OPINION IN MICROBIOLOGY 2014 JUN; 19(?):VIII-X
Markowitz M, Evering TH, Garmon D, Caskey M, La Mar M, Rodriguez K, Sahi V, Palmer S, Prada N, Mohri H
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A Randomized Open-Label Study of 3-Versus 5-Drug Combination Antiretroviral Therapy in Newly HIV-1-Infected Individuals
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES 2014 JUN 1; 66(2):140-147
Background:To understand whether combination antiretroviral therapy (cART) has been optimized, we asked whether 3-drug protease inhibitor (PI)-based cART intensified with raltegravir and maraviroc and initiated during early infection would improve outcomes when compared with similarly applied 3-drug PI-based cART.Methods:Forty newly HIV-1-infected patients were randomized 1:2 to receive 3-drug (N = 14) or 5-drug (N = 26) therapy. The primary end point was the percent of subjects with undetectable plasma viremia using standard reverse transcriptase-polymerase chain reaction and the single copy assay after 48 weeks. Secondary end points included levels of cell-associated HIV-1 DNA and RNA and levels of infectious virus in resting CD4(+) T cells at week 96 and quantitative and qualitative immunologic responses.Results:At 48 weeks, 34 subjects remained on study and are included in the as-treated analysis. Three of 11 (27.3%) in the 3-drug arm and 9 of 21 (42.9%) in the 5-drug arm had plasma HIV-1 RNA levels below detection by both standard reverse transcriptase-polymerase chain reaction and single copy assay (P = 0.46, Fisher exact test). No significant differences in absolute levels of proviral DNA or changes in cell-associated RNA were seen during 96 weeks of therapy. Mean levels of infectious HIV-1 in resting CD4(+) T cells at week 96 in 7 subjects treated with 3-drugs and 13 with 5-drugs were 0.67 and 0.71 infectious units per million, respectively (P = 0.81). No differences were seen in quantitative or qualitative immunologic determinations including markers of immune activation.Conclusions:Intensified 5-drug cART initiated during early infection fails to significantly further impact virologic or immunologic responses beyond those achieved with standard 3-drug PI-based cART.
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.
Abel L, El-Baghdadi J, Bousfiha AA, Casanova JL, Schurr E
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Human genetics of tuberculosis: a long and winding road
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES 2014 JUN 19; 369(1645):?
Only a small fraction of individuals exposed to Mycobacterium tuberculosis develop clinical tuberculosis (TB). Over the past century, epidemiological studies have shown that human genetic factors contribute significantly to this interindividual variability, and molecular progress has been made over the past decade for at least two of the three key TB-related phenotypes: (i) a major locus controlling resistance to infection with M. tuberculosis has been identified, and (ii) proof of principle that severe TB of childhood can result from single-gene inborn errors of interferon-g immunity has been provided; genetic association studies with pulmonary TB in adulthood have met with more limited success. Future genetic studies of these three phenotypes could consider subgroups of subjects defined on the basis of individual (e. g. age at TB onset) or environmental (e. g. pathogen strain) factors. Progress may also be facilitated by further methodological advances in human genetics. Identification of the human genetic variants controlling the various stages and forms of TB is critical for understanding TB pathogenesis. These findings should have major implications for TB control, in the definition of improved prevention strategies, the optimization of vaccines and clinical trials and the development of novel treatments aiming to restore deficient immune responses.
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
Rolo J, de Lencastre H, Miragaia M
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High frequency and diversity of cassette chromosome recombinases (ccr) in methicillin-susceptible Staphylococcus sciuri
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 2014 JUN; 69(6):1461-1469
Previous studies produced evidence that mecA, the determinant of beta-lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA), may have originated in the most primitive and widespread animal commensal species-Staphylococcus sciuri. But how the mecA homologue (mecA1/pbpD) was captured from S. sciuri into the staphylococcal cassette chromosome mec (SCCmec) has remained unclear. To understand the role of S. sciuri in the assembly of SCCmec, we screened 118 methicillin-susceptible S. sciuri isolates for SCCmec central elements-ccr and mec complex (ccrAB, ccrC, mecA, mecI and mecR1)-by dot-blot hybridization. In addition, isolates were typed by PFGE and the chromosomal proximity of SCCmec elements was determined by Southern hybridization. ccr typing was performed by nucleotide sequencing. ccrwere identified in 35% of the isolates (naEuroS=aEuroS41), represented by 24 PFGE types, but ccrC was not found. None of the isolates carried mecA or its regulators, but all isolates carried mecA1/pbpD. In the majority of isolates, ccr and mecA1 were located near orfX, the SCCmec integration site. Moreover, in 31% (naEuroS=aEuroS13) of the ccrAB-carrying strains, ccrAB, mecA1 and orfX colocalized in the chromosome. The nucleotide sequence of ccrA/ccrB was highly diverse, including ccr genes closely related (80%-97%) to those found in MRSA. Our results suggest that S. sciuri was a natural recipient and a rich reservoir of ccr for the assembly of SCCmec. The chromosomal location of mecA1, near orfX, the recognition site of ccr, was probably crucial for its mobilization out of S. sciuri species into SCCmec.
Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, Ero J, Fabjan C, Friedl M, Fruhwirth R, Ghete VM, Hoermann N, Hrubec J, Jeitler M, Kiesenhofer W, Kniinz V, Krammer M, Kratschmer I, Liko D, Mikulec I, Rabady D, Rahbaran B, Rohringer C, Rohringer H, Schoefbeck 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, De 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, Clerbaux B, DeLentdecker 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, OcampoRios AA, 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, Jez P, Lemaitre V, Liao J, Militaru O, Nuttens C, Pagano D, Pin A, Piotrzkowski K, Popov A, Selvaggi M, Vizan Garcia JM, 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, De Jesus Damiao D, De Oliveira Martins C, De Souza SF, Malbouisson H, Malek M, Matos Figueiredo D, Mundim L, Nogima H, Da Silva WLP, Santoro A, Sznajder A, Tonelli Manganote EJ, Vilela Pereira A, Bernardes CA, Dias FA, Tomei TRFP, Gregores EM, Lagana C, Marinho F, Mercadante PG, Novaes SF, Padula S, 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 J, Wang X, Wang Z, Xiao H, Xu M, Asawatangtrakuldee C, Ban Y, Guo Y, Li W, Liu S, Mao Y, Qian SJ, Teng H, Wang D, Zhang L, Zou W, Avila C, Carrillo Montoya CA, Chaparro Sierra LF, Gomez JP, Gomez Moreno B, 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, 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, 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, Gel D, Goerlach U, Goetzmann C, Juillot P, LeBihan AC, Van Hove P, Gadrat S, Beauceron S, Beaupere N, Boudoul G, Brochet S, Chasserat J, Chierici R, Contardo D, Depasse P, ElMamouni 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, 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, Haj Ahmad W, 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, Diez Pardos C, Dooling S, 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, Placakyte R, Raspereza A, Ribeiro Cipriano PM, Riedl C, Ron E, Sahin M, 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, 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, Vanelderen L, Barth C, Baus C, Berger J, Boser C, 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, LobellePardo P, Martschei D, Muller T, Niegel M, Nurnberg A, Oberst O, Ott J, Quast G, Rabbertz K, Ratnikov F, Rcker 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, 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, Swain SK, 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, 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, Hesari H, Jafari A, Khakzad M, Najafabadi M, Mehdiabadi SP, Safarzadeh B, Zeinali M, Grunewald M, Abbrescia M, Barbonea L, Calabria C, Chhibra SS, Colaleo A, Creanza D, De Filippisa 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, Fabbria 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, Musenich R, Tosi S, Benaglia A, De Guio F, Di Matteoa L, Fiorendia 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, Tabarelli De Fatis T, Buontempo S, Cavallo N, De Cosa A, Fabozzia F, Iorio AOM, Lista L, Meola S, Merola M, Paolucci P, Azzi P, Bacchetta N, Bellato M, Bisello D, Branca A, Carlin R, Checchia P, Dorigo T, 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, Simonetto F, Torassa E, Tosi M, Vanini S, Zotto P, Zucchettaa 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, D'Agnolo RT, Dell'Orso R, Fiori F, Foa L, Giassi A, Grippo MT, 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, 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, Demaria N, Mariotti C, Maselli S, Migliore E, Monaco V, Musich M, Obertino MM, Ortona G, 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 Riccaa G, Gobbo B, La Licata C, Maronea M, Montanino D, Penzo A, Schizzi A, Zanetti A, Chang S, Kim TY, Nam SK, 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, La Cruz IHD, Lopez-Fernandez R, Martinez-Ortega J, Sanchez-Hernandez A, Villasenor-Cendejas LM, Carrillo Moreno S, Valencia F, Salazar Ibarguen HA, 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, FerreiraParracho PG, Gallinaro M, RodriguesAntunes J, Seixas J, Varela J, Vischia P, Afanasiev S, Bunin P, 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, Djordjevic M, Ekmedzic M, Krpic D, Milosevic J, Aguilar-Benitez M, Alcaraz Maestre J, Battilana C, Calvo E, Cerrada M, Chamizo Llatas M, Colino N, De Lacruz 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, Fernandez Menendez J, Folgueras S, Gonzalez Caballero I, Lloret Iglesias L, Piedra Gomez J, Cifuentes JAB, Cabrillo IJ, Calderon A, Chuang SH, DuarteCampderros J, Fernandez M, Gomez G, Sanchez JG, Graziano A, Jorda C, LopezVirto A, Marco J, Marco R, Rivero CM, Matorras F, Sanchez FJM, Rodrigo T, Rodriguez-Marrero AY, Ruiz-Jimeno A, Scodellaro L, Vila I, Vilar Cortabitarte R, 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, Da Browski A, 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, Loureno C, Magini N, Malberti M, Malgeri L, Mannelli M, Masetti L, Meijers F, Mersi S, Meschi E, Moneta L, Moser R, Mulders M, Musella P, Nesvold E, Orsini L, Palencia Cortezon E, Perez E, Perrozzi L, Petrilli A, Pfeiffer A, Pierini APM, Pimia M, Piparo D, Plagge M, Polese G, Quertenmont L, Racz A, Reece W, Rolandi G, Rovelli C, 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, Tsirou A, Veres GI, Vlimant JR, Wohri HK, Worm SD, Zeuner WD, Bertl W, Deiters K, Erdmann W, Gabathuler K, Horisberger R, Ingram Q, Kaestli HC, Konig S, Kotlinski D, Langenegger U, Renker D, Rohe T, Bachmair F, Bani L, Bortignon P, Buchmann MA, Casal B, Chanon N, Deisher A, Dissertori G, Dittmar M, Donega M, Dunser M, Eller P, Freudenreich K, Grab C, Hits D, Lecomte P, Lustermann W, Marini AC, del Arbol PMR, Mohr N, Moortgat F, Nageli C, Nef P, Nessi-Tedaldi F, Pandolfi F, Pape L, Pauss F, Peruzzi M, Ronga FJ, Rossini M, Sala L, Sanchez AK, Starodumov A, Stieger B, Takahashi M, Tauscher L, Thea A, Theofilatos K, Treille D, Urscheler C, Wallny R, Weber HA, Amsler C, Chiochia V, Favaro C, Rikova M, Kilminster B, Mejias B, Otiougova P, Robmann P, Snoek H, Taroni S, Tupputi S, Verzetti M, Cardaci M, Chen KH, Ferro C, Kuo CM, Li SW, Lin W, Lu YJ, Volpe R, Yu SS, Bartalini P, Chang P, Chang YH, Chang YW, Chao Y, Chen KF, Dietz C, 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Svyatkovskiy A, VidalMarono M, Wang F, Xu L, Yoo HD, Zablocki J, Zheng Y, Guragain S, Parashar N, Adair A, Akgun B, Ecklund KM, Geurts FJM, Li W, Padley BP, Redjimi R, Roberts J, Zabel J, Betchart B, Bodek A, Covarelli R, Debarbaro 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, Rose K, Salur S, Schnetzer S, Seitz C, Somalwar S, Stone R, Thomas S, Walker M, Cerizza G, Hollingsworth M, 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, Damgov J, Dragoiu C, Dudero PR, 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Observation of a peaking structure in the J/psi phi mass spectrum from B-+/- -> J/psi phi K-+/- decays
PHYSICS LETTERS B 2014 JUN 27; 734(?):261-281
A peaking structure in the J/psi phi mass spectrum near threshold is observed in B-+/- -> J/psi phi K-+/- decays, produced in pp collisions at root s = 7 TeV collected with the CMS detector at the LHC. The data sample, selected on the basis of the dimuon decay mode of the J/psi, corresponds to an integrated luminosity of 5.2 fb(-1). Fitting the structure to an S-wave relativistic Breit-Wigner lineshape above a three-body phase-space nonresonant component gives a signal statistical significance exceeding five standard deviations. The fitted mass and width values are m = 4148.0 +/- 2.4 (stat.) +/- 6.3 (syst.) MeV and Gamma = 28(-11)(+15) (stat.) +/- 19 (syst.) MeV, respectively. Evidence for an additional peaking structure at higher J/psi phi mass is also reported. (C) 2014 The Authors. Published by Elsevier B.V.
Chen CH, Chen WY, Lin SF, Wong RJ
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Epithelial-Mesenchymal Transition Enhances Response to Oncolytic Herpesviral Therapy Through Nectin-1
HUMAN GENE THERAPY 2014 JUN; 25(6):539-551
Cancers exhibiting epithelial-mesenchymal transition (EMT) are associated with aggressive behavior and increased metastatic potential. Therapies that are able to target EMT would have significant clinical value. Nectin-1 is a cell surface herpes simplex virus type 1 (HSV-1) receptor that also forms a component of intercellular adherens junctions, which are typically disrupted in EMT. To explore relationships between HSV-1 sensitivity and EMT, we generated cell lines with a stable EMT phenotype from human follicular thyroid cancer (WRO82-1) through E-cadherin silencing with short hairpin RNA (shEcadWRO). HSV-1 viral attachment and gene expression were both enhanced in shEcadWRO as compared with shControl. Immunoblotting and immunostaining revealed enhanced nectin-1 expression by shEcadWRO. Receptor-blocking assays demonstrated that increased herpesviral entry into shEcadWRO as compared with shControl was mediated predominantly through nectin-1. Colocalization of green fluorescent protein-tagged HSV-1 and tdTomato-tagged nectin-1 confirmed an increase in viral attachment to nectin-1 in shEcadWRO. Cell viability assays demonstrated increased susceptibility of shEcadWRO to HSV-1 oncolysis, and a murine flank tumor model showed significantly enhanced regression of shEcadWRO tumors in response to oncolytic HSV-1 as compared with control tumors. A separate model of EMT induction through transforming growth factor- stimulation confirmed enhanced HSV-1 susceptibility in Panc1 cells. These results demonstrate that the process of EMT leads to increased herpesviral susceptibility through enhanced cell surface nectin-1 expression, suggesting that cancers exhibiting EMT may be naturally sensitive targets for herpesviral therapy.
Romi E, Gokhman I, Wong E, Antonovsky N, Ludwig A, Sagi I, Saftig P, Tessier-Lavigne M, Yaron A
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ADAM metalloproteases promote a developmental switch in responsiveness to the axonal repellant Sema3A
NATURE COMMUNICATIONS 2014 JUN; 5(?):? Article 4058
During embryonic development, axons can gain and lose sensitivity to guidance cues, and this flexibility is essential for the correct wiring of the nervous system. Yet, the underlying molecular mechanisms are largely unknown. Here we show that receptor cleavage by ADAM (A Disintegrin And Metalloprotease) metalloproteases promotes murine sensory axons loss of responsiveness to the chemorepellant Sema3A. Genetic ablation of ADAM10 and ADAM17 disrupts the developmental downregulation of Neuropilin-1 (Nrp1), the receptor for Sema3A, in sensory axons. Moreover, this is correlated with gain of repulsive response to Sema3A. Overexpression of Nrp1 in neurons reverses axonal desensitization to Sema3A, but this is hampered in a mutant Nrp1 with high susceptibility to cleavage. Lastly, we detect guidance errors of proprioceptive axons in ADAM knockouts that are consistent with enhanced response to Sema3A. Our results provide the first evidence for involvement of ADAMs in regulating developmental switch in responsiveness to axonal guidance cues.
Busslinger M, Tarakhovsky A
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Epigenetic Control of Immunity
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY 2014 JUN; 6(6):? Article a019307
Immunity relies on the heterogeneity of immune cells and their ability to respond to pathogen challenges. In the adaptive immune system, lymphocytes display a highly diverse antigen receptor repertoire that matches the vast diversity of pathogens. In the innate immune system, the cell's heterogeneity and phenotypic plasticity enable flexible responses to changes in tissue homeostasis caused by infection or damage. The immune responses are calibrated by the graded activity of immune cells that can vary from yeast-like proliferation to lifetime dormancy. This article describes key epigenetic processes that contribute to the function of immune cells during health and disease.