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Schaefer U
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Pharmacological Inhibition of Bromodomain-Containing Proteins in Inflammation
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY 2014 JUN; 6(6):? Article a018671
Inflammation is associated with the activation of genes that contribute to immune defense and tissue repair. The bromodomain-containing proteins of the BET family, which recognize histone lysine acetylation, play a key role in the transcriptional control of inflammatory genes. Inhibition of BET proteins by the small-molecule inhibitor I-BET affects the expression of a particular subset of inflammatory genes-namely, ones that follow an "analog-like," but not "digital-like" activation pattern. This ability of I-BET to target genes based on the dynamic pattern of their activation may facilitate the further development of anti-inflammatory treatment protocols that are tuned to the individual or to disease-specific patterns of gene expression.
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.
Zhang QR, Long Q, Ott J
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AprioriGWAS, a New Pattern Mining Strategy for Detecting Genetic Variants Associated with Disease through Interaction Effects
PLOS COMPUTATIONAL BIOLOGY 2014 JUN; 10(6):? Article e1003627
Identifying gene-gene interaction is a hot topic in genome wide association studies. Two fundamental challenges are: (1) how to smartly identify combinations of variants that may be associated with the trait from astronomical number of all possible combinations; and (2) how to test epistatic interaction when all potential combinations are available. We developed AprioriGWAS, which brings two innovations. (1) Based on Apriori, a successful method in field of Frequent Itemset Mining (FIM) in which a pattern growth strategy is leveraged to effectively and accurately reduce search space, AprioriGWAS can efficiently identify genetically associated genotype patterns. (2) To test the hypotheses of epistasis, we adopt a new conditional permutation procedure to obtain reliable statistical inference of Pearson's chi-square test for the 2 x f contingency table generated by associated variants. By applying AprioriGWAS to age-related macular degeneration (AMD) data, we found that: (1) angiopoietin 1 (ANGPT1) and four retinal genes interact with Complement Factor H (CFH). (2) GO term "glycosaminoglycan biosynthetic process" was enriched in AMD interacting genes. The epistatic interactions newly found by AprioriGWAS on AMD data are likely true interactions, since genes interacting with CFH are retinal genes, and GO term enrichment also verified that interaction between glycosaminoglycans (GAGs) and CFH plays an important role in disease pathology of AMD. By applying AprioriGWAS on Bipolar disorder in WTCCC data, we found variants without marginal effect show significant interactions. For example, multiple-SNP genotype patterns inside gene GABRB2 and GRIA1 (AMPA subunit 1 receptor gene). AMPARs are found in many parts of the brain and are the most commonly found receptor in the nervous system. The GABRB2 mediates the fastest inhibitory synaptic transmission in the central nervous system. GRIA1 and GABRB2 are relevant to mental disorders supported by multiple evidences.
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.
Liu ZH, Frutos S, Bick MJ, Vila-Perello M, Debelouchina GT, Darst SA, Muir TW
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Structure of the branched intermediate in protein splicing
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2014 JUN 10; 111(23):8422-8427
Inteins are autoprocessing domains that cut themselves out of host proteins in a traceless manner. This process, known as protein splicing, involves multiple chemical steps that must be coordinated to ensure fidelity in the process. The committed step in splicing involves attack of a conserved Asn side-chain amide on the adjacent backbone amide, leading to an intein-succinimide product and scission of that peptide bond. This cleavage reaction is stimulated by formation of a branched intermediate in the splicing process. The mechanism by which the Asn side-chain becomes activated as a nucleophile is not understood. Here we solve the crystal structure of an intein trapped in the branched intermediate step in protein splicing. Guided by this structure, we use protein-engineering approaches to show that intein-succinimide formation is critically dependent on a backbone-to-side-chain hydrogen-bond. We propose that this interaction serves to both position the side-chain amide for attack and to activate its nitrogen as a nucleophile. Collectively, these data provide an unprecedented view of an intein poised to carry out the rate-limiting step in protein splicing, shedding light on how a nominally nonnucleophilic group, a primary amide, can become activated in a protein active site.
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, 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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.
Charpentier E, Marraffini LA
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Harnessing CRISPR-Cas9 immunity for genetic engineering
CURRENT OPINION IN MICROBIOLOGY 2014 JUN; 19(?):114-119
CRISPR-Cas encodes an adaptive immune system that defends prokaryotes against infectious viruses and plasmids. Immunity is mediated by Cas nucleases, which use small RNA guides (the crRNAs) to specify a cleavage site within the genome of invading nucleic acids. In type II CRISPR-Cas systems, the DNA-cleaving activity is performed by a single enzyme Cas9 guided by an RNA duplex. Using synthetic single RNA guides, Cas9 can be reprogrammed to create specific double-stranded DNA breaks in the genomes of a variety of organisms, ranging from human cells to bacteria, and thus constitutes a powerful tool for genetic engineering. Here we describe recent advancements in our understanding of type II CRISPR-Cas immunity and how these studies led to revolutionary genome editing applications.
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Search for new physics in the multijet and missing transverse momentum final state in proton-proton collisions at root s=8 Tev
JOURNAL OF HIGH ENERGY PHYSICS 2014 JUN 10; ?(6):? Article 055
A search for new physics is performed in multijet events with large missing transverse momentum produced in proton-proton collisions at root s = 8TeV using a data sample corresponding to an integrated luminosity of 19.5 fb(-1) collected with the CMS detector at the LHC. The data sample is divided into three jet multiplicity categories (3-5, 6-7, and >= 8 jets), and studied further in bins of two variables: the scalar sum of jet transverse momenta and the missing transverse momentum. The observed numbers of events in various categories are consistent with backgrounds expected from standard model processes. Exclusion limits are presented for several simplified supersymmetric models of squark or gluino pair production.
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Measurement of the t-channel single-top-quark production cross section and of the |V (tb)| CKM matrix element in pp collisions at root s=8 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2014 JUN 16; ?(6):? Article 090
Measurements are presented of the t-channel single-top-quark production cross section in proton-proton collisions at root s = 8 TeV. The results are based on a data sample corresponding to an integrated luminosity of 19.7 fb(-1) recorded with the CMS detector at the LHC. The cross section is measured inclusively, as well as separately for top (t) and antitop (t) over bar, in final states with a muon or an electron. The measured inclusive t-channel cross section is sigma(t-ch.) = 83.6 +/- 2.3 (stat.) +/- 7.4 (syst.) pb. The single t and (t) cross sections are measured to be sigma(t-ch.)(t) = 53.8 +/- 1.5 (stat.) +/- 4.4 (syst.) pb and sigma(t-ch.)(t) over bar = 27.6 +/- 1.3 (stat.) +/- 3.7 (syst.) pb, respectively. The measured ratio of cross sections is Rt-ch. = sigma(t-ch.)(t)/sigma(t-ch.)(t) over bar = 1.95 +/- 0.10 (stat.) +/- 0.19 (syst.), in agreement with the standard model prediction. The modulus of the Cabibbo-Kobayashi-Maskawa matrix element V-tb is extracted and, in combination with a previous CMS result at root s = 7 TeV, a value vertical bar V-tb vertical bar = 0.998 +/- 0.038 (exp.) +/- 0.016 (theo.) is obtained.