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Found 37769 matches. Displaying 5431-5440
Tsou LK, Lara-Tejero M, RoseFigura J, Zhang ZRJ, Wang YC, Yount JS, Lefebre M, Dossa PD, Kato J, Guan FL, Lam W, Cheng YC, Galan JE, Hang HC
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Antibacterial Flavonoids from Medicinal Plants Covalently Inactivate Type III Protein Secretion Substrates
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2016 FEB 24; 138(7):2209-2218
Traditional Chinese Medicines (TCMs) have been historically used to treat bacterial infections. However, the molecules responsible for these anti-infective properties and their potential mechanisms of action have remained elusive. Using a high-throughput assay for type III protein secretion in Salmonella enterica serovar Typhimurium, we discovered that several TCMs can attenuate this key virulence pathway without affecting bacterial growth. Among the active TCMs, we discovered that baicalein, a specific flavonoid from Scutellaria baicalensis, targets S. Typhimurium pathogenicity island-1 (SPI-1) type III secretion system (T3SS) effectors and translocases to inhibit bacterial invasion of epithelial cells. Structurally related flavonoids present in other TCMs, such as quercetin, also inactivated the SPI-1 T3SS and attenuated S. Typhimurium invasion. Our results demonstrate that specific plant metabolites from TCMs can directly interfere with key bacterial virulence pathways and reveal a previously unappreciated mechanism of action for anti-infective medicinal plants.
Frugoni F, Dobbs K, Felgentreff K, Aldhekri H, Al Saud BK, Arnaout R, Ali AA, Abhyankar A, Alroqi F, Giliani S, Ojeda MM, Tsitsikov E, Pai SY, Casanova JL, Notarangelo LD, Manis JP
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A novel mutation in the POLE2 gene causing combined immunodeficiency
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 2016 FEB; 137(2):635-638
Fava VM, Manry J, Cobat A, Orlova M, Thuc NV, Ba NN, Thai VH, Abel L, Alcais A, Schurr E
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A Missense LRRK2 Variant Is a Risk Factor for Excessive Inflammatory Responses in Leprosy
PLOS NEGLECTED TROPICAL DISEASES 2016 FEB; 10(2):? Article e0004412
Background Depending on the epidemiological setting, a variable proportion of leprosy patients will suffer from excessive pro-inflammatory responses, termed type-1 reactions (T1R). The LRRK2 gene encodes a multi-functional protein that has been shown to modulate pro-inflammatory responses. Variants near the LRRK2 gene have been associated with leprosy in some but not in other studies. We hypothesized that LRRK2 was a T1R susceptibility gene and that inconsistent association results might reflect different proportions of patients with T1R in the different sample settings. Hence, we evaluated the association of LRRK2 variants with T1R susceptibility. Methodology An association scan of the LRRK2 locus was performed using 156 single-nucleotide poly-morphisms (SNPs). Evidence of association was evaluated in two family-based samples: A set of T1R-affected and a second set of T1R-free families. Only SNPs significant for T1R-affected families with significant evidence of heterogeneity relative to T1R-free families were considered T1R-specific. An expression quantitative trait locus (eQTL) analysis was applied to evaluate the impact of T1R-specific SNPs on LRRK2 gene transcriptional levels. Principal Findings A total of 18 T1R-specific variants organized in four bins were detected. The core SNP capturing the T1R association was the LRRK2 missense variant M2397T (rs3761863) that affects LRRK2 protein turnover. Additionally, a bin of nine SNPs associated with T1R were eQTLs for LRRK2 in unstimulated whole blood cells but not after exposure to Mycobacterium leprae antigen. Significance The results support a preferential association of LRRK2 variants with T1R. LRRK2 involvement in T1R is likely due to a pathological pro-inflammatory loop modulated by LRRK2 availability. Interestingly, the M2397T variant was reported in association with Crohn's disease with the same risk allele as in T1R suggesting common inflammatory mechanism in these two distinct diseases.
Nguyen A, Loo JM, Mital R, Weinberg EM, Man FY, Zeng ZS, Paty PB, Saltz L, Janjigian YY, de Stanchina E, Tavazoie SF
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PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis
JOURNAL OF CLINICAL INVESTIGATION 2016 FEB; 126(2):681-694
Colorectal cancer metastasis to the liver is a major cause of cancer-related death; however, the genes and pathways that govern this metastatic colonization event remain poorly characterized. Here, using a large-scale in vivo RNAi screen, we identified liver and red blood cell pyruvate kinase (PKLR) as a driver of metastatic liver colonization. PKLR expression was increased in liver metastases as well as in primary colorectal tumors of patients with metastatic disease. Evaluation of a murine liver colonization model revealed that PKLR promotes cell survival in the tumor core during conditions of high cell density and oxygen deprivation by increasing glutathione, the primary endogenous antioxidant. PKLR negatively regulated the glycolytic activity of PKM2, the major pyruvate kinase isoenzyme known to regulate cellular glutathione levels. Glutathione is critical for metastasis, and we determined that the rate-limiting enzyme of glutathione synthesis, GCLC, becomes overexpressed in patient liver metastases, promotes cell survival under hypoxic and cell-dense conditions, and mediates metastatic liver colonization. RNAi-mediated inhibition of glutathione synthesis impaired survival of multiple colon cancer cell lines, and pharmacological targeting of this metabolic pathway reduced colonization in a primary patient-derived xenograft model. Our findings highlight the impact of metabolic reprogramming within the niche as metastases progress and suggest clinical potential for targeting this pathway in colorectal cancer.
Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, Brandstetter J, Brondolin E, Dragicevic M, Eroe J, Flechl M, Friedl M, Fruehwirth R, Ghete VM, Hart C, Hoermann N, Hrubec J, Jeitler M, Knuenz V, Koenig A, KrammerJ M, Kraetschmer I, Liko D, Matsushita T, Mikulec I, Rabady D, Rahbaran B, Rohringer H, Schieck J, Schoefbeck 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, De Klundert MV, Van Haevermaet H, Van Mechelen R, 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 R, Van Onsem GP, Van Parijs I, Barria R, Caillol C, Clerbaux B, De Lentdecker G, Delannoy H, Dobur D, 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, Velde CV, Vanlaer R, Yonamine R, Zenoni F, Zhang F, Beernaert K, Benucci L, Cimmino A, Crucy S, Fagot A, Garcia G, Mccartin MGJ, 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 R, 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, Martins TDR, Hensel C, Herrera CM, Moraes A, Pol ME, Teles RR, 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 AD, 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 R, Piperov S, Rodozov M, Stoykova S, Sultanov G, Vutova M, Dimitrov A, Glushkov I, Litov L, Pavlov B, Petkov R, 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, Asawatangtrakuldee C, 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, 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, Aly R, Aly S, El-Khateeb E, Lotfy A, Mohamed A, Radi A, Salama E, Sayed A, Calpas B, Kadastik M, Murumaa M, Raidal M, Tiko A, Veelken C, Eerola R, Pekkanen J, Voutilainen M, Harkonen J, Karimaki V, Kinnunen R, Lampen T, Lassila-Perini K, Lehti S, Linden T, Luukka R, 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 R, De Monchenault GH, Jarry R, Locci E, Machet M, Malcles J, Rander J, Rosowsky A, Titov M, Zghiche A, Antropov I, Baffioni S, Beaudette F, Busson R, Cadamuro L, Chapon E, Chariot C, Dahms T, Davignon O, Filipovic N, Florent A, De Cassagnac RG, Lisniak S, Mastrolorenzo L, Mine R, Naranjo IN, Nguyen M, Ochando C, Ortona G, Paganini R, 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, Collard NCC, Conte E, Coubez X, Fontaine JC, Gele D, Goerlach U, Goetzmann C, Le Bihan AC, Merlin JA, Skovpen K, Van Hove R, Gadrat S, Beauceron S, Bernet C, Boudoul G, Bouvier E, Montoya CAC, Chasserat J, Chierici R, Contardo D, Courbon B, Depasse R, El Mamouni H, Fan J, Fay J, Gascon S, Gouzevitch M, Ille B, Laktineh IB, Lethuillier M, Mirabito L, Pequegnot AL, Perries S, Alvarez JDR, Sabes D, Sgandurra L, Sordini V, Donckt MV, Verdier R, 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, Sammet J, 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, Gueth A, Hebbeker T, Heidemann C, Hoepfner K, Klingebiel D, Knutzen S, Kreuzer R, Merschmeyer M, Meyer A, Millet R, Olschewski M, Padeken K, Papacz R, Pook T, Radziej M, Reithler H, Rieger M, Scheuch F, Sonnenschein L, Teyssier D, Thuer S, Cherepanov V, Erdogan Y, Fluegge G, Geenen H, Geisler M, Hoehle F, Kargoll B, Kuessel TKY, Kuensken 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 R, Hauk J, Hempel M, Jung H, Kalogeropoulos A, Karacheban O, Kasemann M, Katsas R, 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, Mussgiller JMA, Naumann-Emme S, Nayak A, Ntomari E, Perrey H, Pitzl D, Placakyte R, Raspereza A, Cipriano PMR, Roland B, Sahin MO, Saxena R, Schoerner-Sadenius T, Schroder M, Seitz C, Spannagel S, Trippkewitz KD, 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 R, Schlieckau E, Schmidt A, Schwandt J, Seidel M, Sola V, Stadie H, Steinbrueck G, Tholen H, Troendle D, Vanelderen EUL, Vanhoefer A, Akbiyik M, Barth C, Baus C, Berger J, Boeser C, Butz E, Chwalek T, Colombo F, De Boer W, Descroix A, Dierlamm A, Feindt M, Frensch F, Giffels M, Gilbert A, Hartmann F, Husemann U, Kassel F, Katkov I, Kornmayer A, Pardo RL, 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, 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 R, Loukas N, Manthos N, Papadopoulos I, Paradas E, Strologas J, Bencze G, Hajdu C, Hazi A, Hidas R, 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 R, Trocsanyi ZL, Ujvari B, Mal R, 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, Nishu N, Singh JB, Walia G, Kumar A, Kumar A, Bhardwaj A, Choudhary BC, Garg RB, Kumar A, Malhotra S, Naimuddin M, Ranjan K, Sharma R, Sharma V, Banerjee S, Bhattacharya S, Chatterjee K, Dey S, Dutta S, Jain S, Jain S, Khurana R, 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 R, Topkar A, Aziz T, Banerjee S, Bhowmik S, Chatterjee RM, Dewanjee RK, Ganguly SDS, 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, 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 R, Abbiendi G, Battilana C, Benvenuti AC, Bonacorsi D, Braibant-Giacomelli S, Brigliadori L, Campanini R, Capiluppi R, Castro A, Cavallo FR, Codispoti G, Cuffiani M, Dallavalle GM, Fabbri F, Fanfani A, Fasanella D, Giacomelli R, 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 R, 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 R, 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 R, Sciacca C, Thyssen F, Bacchetta N, Bisello D, Boletti A, Carlin R, De Oliveira ACA, Checchia R, Dall'Osso M, Fanzago F, Gasparini F, Gasparini U, Gonella F, Gozzelino A, Kanishchev K, Margoni M, Maron G, Meneguzzo AT, Montecassiano F, Passaseo M, Pazzini J, Pozzobon N, Ronchese R, Simonetto F, Torassa E, Tosia M, Zanetti M, Zotto R, Zucchetta A, Zumerle G, Braghieri A, Magnani A, Montagna R, Ratti SP, Re V, Riccardi C, Salvini R, Vai I, Vitulo R, Solestizi LA, Biasini M, Bilei GM, Ciangottini D, Fano L, Lariccia R, Mantovani G, Menichelli M, Saha A, Santocchia A, Spiezia A, Androsov K, Azzurri R, 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 R, Micheli F, Organtini G, Paramatti R, Preiato F, Rahatlou S, Rovelli C, Santanastasio F, Traczyk R, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Bellan R, Biino C, Cartiglia N, Costa M, Covarelli R, Degano A, Demaria N, Dughera G, Finco L, 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, Linares EC, Castilla-Valdez H, De la Cruz-Burelo E, la Cruz IHD, 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 R, Brona G, Bunkowski K, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Olszewski M, Walczak M, Bargassa R, Silva CBDCE, Di Francesco A, Faccioli R, Parracho PGF, Gallinaro M, Leonardo N, Iglesias LL, Nguyen F, Antunes JR, Seixas J, Toldaiev O, Vadruccio D, Varela J, Vischia R, Afanasiev S, Bunin R, Gavrilenko M, Golutvin I, Gorbunov I, Kamenev A, Karjavin V, Konoplyanikov V, Laney A, Malakhov A, Matveev V, Moisenz R, Palichik V, Perelygin V, Shmatov S, Shulha S, Skatchkov N, Smirnov V, Zarubin A, Golovtsov V, Ivanov Y, Kim V, Kuznetsova E, Levchenko R, Murzin V, Oreshkin V, Smirnov I, Sulimov V, Uvarov L, Vavilov S, Vorobyev A, Andreev Y, Dermenev A, Gninenko S, Golubev N, Karneyeu A, Kirsanov M, Krasnikov N, Pashenkov A, Tlisov D, Toropin A, Epshteyn V, Gavrilov V, Lychkovskaya N, Popov V, Pozdnyakov I, Safronov G, Spiridonov A, Vlasov E, Zhokin A, Bylinkin A, Andreev V, Azarkin M, Dremin I, Kirakosyan M, Leonidov A, Mesyats G, Rusakov SV, Vinogradov A, Baskakov A, Belyaev A, Boos E, Dubinin M, Dudko L, Ershov A, Gribushin A, Klyukhin V, Kodolova O, Lokhtin I, Myagkov I, Obraztsov S, Petrushanko S, Savrin V, Snigirev A, Azhgirey I, Bayshev I, Bitioukov S, Kachanov V, Kalinin A, Konstantinov D, 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Garcia-Bellido A, Goldenzweig R, Han J, Harel A, Hindrichs O, Khukhunaishvili A, Petrillo G, Verzetti M, Demortier L, Arora S, Barker A, Chou JP, Contreras-Campana C, Contreras-Campana E, Duggan D, Ferencek D, Gershtein Y, Gray R, Halkiadakis E, Hidas D, Hughes E, Kaplan S, Elayavalli RK, Lath A, Panwalkar S, Park M, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen R, Walker M, Foerster M, Riley G, Rose K, Spanier S, York A, Bouhali O, Hernandez AC, Dalchenko M, De Mattia M, Delgado A, Dildick S, Eusebi R, Flanagan W, Gilmore J, Kamon T, Krutelyov V, Montalvo R, Mueller R, Osipenkov I, Pakhotin Y, Patel R, Perloff A, Roe J, Rose A, Safonov A, Tatarinov A, Ulmer KA, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero PR, Faulkner J, Kunori S, Lamichhane K, Lee SW, Libeiro T, Undleeb S, Volobouev I, Appelt E, Delannoy AG, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Mao Y, Melo A, Sheldon R, Snook B, Tuo S, Velkovska J, Xu Q, Arenton MW, Boutle S, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Lin C, Neu C, Wolfe E, Wood J, Xia F, Clarke C, Harr R, Karchin PE, Don CKK, Lamichhane R, Sturdy J, Belknap DA, Carlsmith D, Cepeda M, Christian A, Dasu S, Dodd L, Duric S, Friis E, Gomber B, Hall-Wilton R, Herndon M, Herve A, Klabbers R, Lanaro A, Levine A, Long K, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ross I, Ruggles T, Sarangi T, Savin A, Sharma A, Smith N, Smith WH, Taylor D, Woods N
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Search for a Higgs boson decaying into gamma*gamma -> ll gamma with low dilepton mass in pp collisions at root s=8 TeV
PHYSICS LETTERS B 2016 FEB 10; 753(?):341-362
A search is described for a Higgs boson decaying into two photons, one of which has an internal conversion to a muon or an electron pair (ll gamma). The analysis is performed using proton-proton collision data recorded with the CMS detector at the LHC at a centre-of-mass energy of 8TeV, corresponding to an integrated luminosity of 19.7 fb(-1). The events selected have an opposite-sign muon or electron pair and a high transverse momentum photon. No excess above background has been found in the three-body invariant mass range 120 < m(ll gamma) < 150 GeV, and limits have been derived for the Higgs boson production cross section times branching fraction for the decay H -> gamma*gamma -> ll gamma, where the dilepton invariant mass is less than 20 GeV. For a Higgs boson with m(H) = 125 GeV, a 95% confidence level (CL) exclusion observed (expected) limit is 6.7 (5.9(-1.8)(+2.8)) times the standard model prediction. Additionally, an upper limit at 95% CL on the branching fraction of H -> (J/psi)gamma for the 125 GeV Higgs boson is set at 1.5 x10(-3). (C) 2015 CERN for the benefit of the CMS Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Haka AS, Sue E, Zhang C, Bhardwaj P, Sterling J, Carpenter C, Leonard M, Manzoor M, Walker J, Aleman JO, Gareau D, Holt PR, Breslow JL, Zhou XK, Giri D, Morrow M, Iyengar N, Barman I, Hudis CA, Dannenberg AJ
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Noninvasive Detection of Inflammatory Changes in White Adipose Tissue by Label-Free Raman Spectroscopy
ANALYTICAL CHEMISTRY 2016 FEB 16; 88(4):2140-2148
White adipose tissue inflammation (WATi) has been linked to the pathogenesis of obesity-related diseases, including type 2 diabetes, cardiovascular disease, and cancer. In addition to the obese, a substantial number of normal and overweight individuals harbor WATi, putting them at increased risk for disease. We report the first technique that has the potential to detect WATi noninvasively. Here, we used Raman spectroscopy to detect WATi with excellent accuracy in both murine and human tissues. This is a potentially significant advance over current histopathological techniques for the detection of WATi, which rely on tissue excision and, therefore, are not practical for assessing disease risk in the absence of other identifying factors. Importantly, we show that noninvasive Raman spectroscopy can diagnose WATi in mice. Taken together, these results demonstrate the potential of Raman spectroscopy to provide objective risk assessment for future cardiometabolic complications in both normal weight and overweight/obese individuals.
Sontheimer EJ, Marraffini LA
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CRISPR goes retro
SCIENCE 2016 FEB 26; 351(6276):920-921
Barson JR, Leibowitz SF
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Hypothalamic neuropeptide signaling in alcohol addiction
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY 2016 FEB 4; 65(?):?
The hypothalamus is now known to regulate alcohol intake in addition to its established role in food intake, in part through neuromodulatory neurochemicals termed neuropeptides. Certain orexigenic neuropeptides act in the hypothalamus to promote alcohol drinking, although they affect different aspects of the drinking response. These neuropeptides, which include galanin, the endogenous opioid enkephalin, and orexin/ hypocretin, appear to stimulate alcohol intake not only through mechanisms that promote food intake but also by enhancing reward and reinforcement from alcohol. Moreover, these neuropeptides participate in a positive feedback relationship with alcohol, whereby they are upregulated by alcohol intake to promote even further consumption. They contrast with other orexigenic neuropeptides, such as melanin-concentrating hormone and neuropeptide Y, which promote alcohol intake under limited circumstances, are not consistently stimulated by alcohol, and do not enhance reward. They also contrast with neuropeptides that can be anorexigenic, including the endogenous opioid dynorphin, corticotropin-releasing factor, andmelanocortins, which act in the hypothalamus to inhibit alcohol drinking as well as reward and therefore counter the ingestive drive promoted by orexigenic neuropeptides. Thus, while multiple hypothalamic neuropeptides may work together to regulate different aspects of the alcohol drinking response, excessive signaling from orexigenic neuropeptides or inadequate signaling from anorexigenic neuropeptides can therefore allow alcohol drinking to become dysregulated. (C) 2015 Elsevier Inc. All rights reserved.
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Perry T, Pierro GA, Polese G, Ross I, Ruggles T, Sarangi T, Savin A, Smith N, Smith WH, Taylor D, Woods N
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Search for a massive resonance decaying into a Higgs boson and a W or Z boson in hadronic final states in proton-proton collisions at root s=8 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2016 FEB 22; ?(2):? Article 145
A search for a massive resonance decaying into a standard-model-like Higgs boson (H) and a W or Z boson is reported. The analysis is performed on a data sample corresponding to an integrated luminosity of 19.7 fb(-1), collected in proton-proton collisions at a centre-of-mass energy of 8 TeV with the CMS detector at the LHC. Signal events, in which the decay products of Higgs, W, or Z bosons at high Lorentz boost are contained within single reconstructed jets, are identified using jet substructure techniques, including the tagging of b hadrons. This is the first search for heavy resonances decaying into HW or HZ resulting in an all-jet final state, as well as the first application of jet substructure techniques to identify H -> WW* -> 4q decays at high Lorentz boost. No significant signal is observed and limits are set at 95% confidence level on the production cross sections of W' and Z' in a model with mass-degenerate charged and neutral spin-1 resonances. Resonance masses are excluded for W' in the interval [1.0, 1.6] TeV, for Z' in the intervals [1.0, 1.1] and [1.3, 1.5] TeV, and for mass-degenerate W' and Z' in the interval [1.0, 1.7] TeV.
Ghose C, Eugenis I, Edwards AN, Sun XM, McBride SM, Ho DD
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Immunogenicity and protective efficacy of Clostridium difficile spore proteins
ANAEROBE 2016 FEB; 37(?):85-95
Clostridium difficile is a spore-forming, anaerobic, Gram-positive organism that is the leading cause of antibiotic-associated infectious diarrhea, commonly known as C difficile infection (CDI). C difficile spores play an important role in the pathogenesis of CDI. Spore proteins, especially those that are surface-bound may play an essential role in the germination, colonization and persistence of C difficile in the human gut. In our current study, we report the identification of two surface-bound spore proteins, CdeC and CdeM that may be utilized as immunization candidates against C difficile. These spore proteins are immunogenic in mice and are able to protect mice against challenge with C. difficile UK1, a clinically relevant 027/B1/NAP1 strain. These spore proteins are also able to afford high levels of protection against challenge with C difficile 630 Delta erm in golden Syrian hamsters. This unprecedented study shows the vaccination potential of C difficile spore exosporium proteins. (C) 2015 Elsevier Ltd. All rights reserved.