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Chang GQ, Karatayev O, Barson JR, Liang SC, Leibowitz SF
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COMMON EFFECTS OF FAT, ETHANOL, AND NICOTINE ON ENKEPHALIN IN DISCRETE AREAS OF THE BRAIN
NEUROSCIENCE 2014 SEP 26; 277(?):665-678
Fat, ethanol, and nicotine share a number of properties, including their ability to reinforce behavior and produce overconsumption. To test whether these substances act similarly on the same neuronal populations in specific brain areas mediating these behaviors, we administered the substances short-term, using the same methods and within the same experiment, and measured their effects, in areas of the hypothalamus (HYPO), amygdala (AMYG), and nucleus accumbens (NAc), on mRNA levels of the opioid peptide, enkephalin (ENK), using in situ hybridization and on c-Fos immunoreactivity (ir) to indicate neuronal activity, using immunofluorescence histochemistry. In addition, we examined for comparison another reinforcing substance, sucrose, and also took measurements of stress-related behaviors and circulating corticosterone (CORT) and triglycerides (TG), to determine if they contribute to these substances' behavioral and physiological effects. Adult Sprague-Dawley rats were gavaged three times daily over 5 days with 3.5 mL of water, Intralipid (20% v/v), ethanol (12% v/v), nicotine (0.01% w/v) or sucrose (22% w/v) (approximately 7 kcal/dose), and tail vein blood was collected for measurements of circulating CORT and TG. On day five, animals were sacrificed, brains removed, and the HYPO, AMYG, and NAc processed for single- or double-labeling of ENK mRNA and c-Fos-ir. Fat, ethanol, and nicotine, but not sucrose, increased the single- and double-labeling of ENK and c-Fos-ir in precisely the same brain areas, the middle parvocellular but not lateral area of the paraventricular nucleus, central but not basolateral nucleus of the AMYG, and core but not shell of the NAc. While having little effect on stress-related behaviors or CORT levels, fat, ethanol, and nicotine all increased circulating levels of TG. These findings suggest that the overconsumption of these three substances and their potential for abuse are mediated by the same populations of ENK-expressing neurons in specific nuclei of the hypothalamus and limbic system. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
Milshteyn A, Schneider JS, Brady SF
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Mining the Metabiome: Identifying Novel Natural Products from Microbial Communities
CHEMISTRY & BIOLOGY 2014 SEP 18; 21(9):1211-1223
Microbial-derived natural products provide the foundation for most of the chemotherapeutic arsenal available to contemporary medicine. In the face of a dwindling pipeline of new lead structures identified by traditional culturing techniques and an increasing need for new therapeutics, surveys of microbial biosynthetic diversity across environmental metabiomes have revealed enormous reservoirs of as yet untapped natural products chemistry. In this review, we touch on the historical context of microbial natural product discovery and discuss innovations and technological advances that are facilitating culture-dependent and culture-independent access to new chemistry from environmental microbiomes with the goal of reinvigorating the small molecule therapeutics discovery pipeline. We highlight the successful strategies that have emerged and some of the challenges that must be overcome to enable the development of high-throughput methods for natural product discovery from complex microbial communities.
von Beeren C, Mair MM, Witte V
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Discovery of a second mushroom harvesting ant (Hymenoptera: Formicidae) in Malayan tropical rainforests
MYRMECOLOGICAL NEWS 2014 SEP; 20(?):37-42
Ants have evolved an amazing variety of feeding habits to utilize diverse food sources. However, only one ant species, Euprenolepis pro cera (EMERY, 1900) (Formicidae: Formicinae), has been described as a specialist harvester of wild-growing mushrooms. Mushrooms are a very abundant food source in certain habitats, but utilizing them is expected to require specific adaptations. Here, we report the discovery of another, sympatric, and widespread mushroom harvesting ant, Euprenolepis wittei LAPOLLA, 2009. The similarity in nutritional niches of both species was expected to be accompanied by similarities in adaptive behavior and differences due to competitive avoidance. Similarities were found in mushroom acceptance and harvesting behavior: Both species harvested a variety of wild-growing mushrooms and formed characteristic mushroom piles inside the nest that were processed continuously by adult workers. Euprenolepis procera was apparently dominant at mushroom baits displacing the smaller, less numerous E. wittei foragers. However, interspecific competition for mushrooms is likely relaxed by differences in other niche dimensions, particularly the temporal activity pattern. The discovery of a second, widespread mushroom harvesting ant suggests that this life style is more common than previously thought, at least in Southeast Asia, and has implications for the ecology of tropical rainforests. Exploitation of the reproductive organs of fungi likely impacts spore development and distribution and thus affects the fungal community.
Rieux-Laucat F, Casanova JL
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Autoimmunity by haploinsufficiency
SCIENCE 2014 SEP 26; 345(6204):1560-1561
Van Kempen TA, Gorecka J, Gonzalez AD, Soeda F, Milner TA, Waters EM
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Characterization of Neural Estrogen Signaling and Neurotrophic Changes in the Accelerated Ovarian Failure Mouse Model of Menopause
ENDOCRINOLOGY 2014 SEP; 155(9):3610-3623
Accelerated ovarian failure (AOF) can be induced in young mice with low doses of 4-vinylcyclohexene diepoxide (VCD), modeling the hormone changes observed across menopause. We assessed markers of synaptic plasticity in the hippocampus, anxiety-like behavior, and spatial learning longitudinally at 4 time points across the AOF model: premenopause, early perimenopause, late perimenopause, and postmenopause (POST). As others have shown, VCD administration decreased ovarian follicle counts and increased acyclicity as the model progressed to POST but with no impact on organ or body weights. The morphology of Iba1 immunoreactive microglia did not differ between vehicle- and VCD-administered mice. Hippocampal postsynaptic density 95 levels were minimally altered across the AOF model but decreased at POST in CA3b 24 hours after exogenous estradiol benzoate (EB). In contrast, hippocampal phosphorylated AKT levels transiently decreased in premenopause but increased at POST after 24 hours of EB in select subregions. Electron microscopy revealed fewer estrogen receptor alpha containing dendritic spines and terminals in CA1 stratum radiatum at POST. mRNA levels of most brain-derived neurotrophic factor exons (except V and VI) were lower in POST compared with ovariectomized mice. Exon V was sensitive to 24 hours of EB administration in POST-VCD. Anxiety-like behavior was unaffected at any menopause phase. Spatial learning was unaffected in all groups, but POST-VCD mice performed below chance. Our results suggest that the AOF model is suitable for longitudinal studies of neurobiological changes across the menopause transition in mice. Our findings also point to complex interactions between estrogen receptors and pathways involved in synaptic plasticity.
Venkataswamy MM, Ng TW, Kharkwal SS, Carreno LJ, Johnson AJ, Kunnath-Velayudhan S, Liu Z, Bittman R, Jervis PJ, Cox LR, Besra GS, Wen XS, Yuan WM, Tsuji M, Li XM, Ho DD, Chan J, Lee S, Frothingham R, Haynes BF, Panas MW, Gillard GO, Sixsmith JD, Korioth-Schmitz B, Schmitz JE, Larsen MH, Jacobs WR, Porcelli SA
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Improving Mycobacterium bovis Bacillus Calmette-Guerin as a Vaccine Delivery Vector for Viral Antigens by Incorporation of Glycolipid Activators of NKT Cells
PLOS ONE 2014 SEP 25; 9(9):? Article e108383
Recombinant Mycobacterium bovis bacillus Calmette-Guerin (rBCG) has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, various strategies are being employed to improve its ability to prime CD8(+) T cells, which play an important role in the control of HIV infections. In this study we adopted a previously described approach of incorporating glycolipids that activate CD1d-restricted natural killer T (NKT) cells to enhance priming of CD8(+) T cells by rBCG strains expressing an SIV Gag antigen (rBCG-SIV gag). We found that the incorporation of the synthetic NKT activating glycolipid alpha-galactosylceramide (alpha-GC) into rBCG-SIV gag significantly enhanced CD8(+) T cell responses against an immunodominant Gag epitope, compared to responses primed by unmodified rBCG-SIV gag. The abilities of structural analogues of alpha-GC to enhance CD8(+) T cell responses to rBCG were compared in both wild type and partially humanized mice that express human CD1d molecules in place of mouse CD1d. These studies identified an alpha-GC analogue known as 7DW8-5, which has previously been used successfully as an adjuvant in non-human primates, as a promising compound for enhancing immunogenicity of antigens delivered by rBCG. vectors. Our findings support the incorporation of synthetic glycolipid activators of NKT cells as a novel approach to enhance the immunogenicity of rBCG-vectored antigens for induction of CD8(+) T cell responses. The glycolipid adjuvant 7DW8-5 may be a promising candidate for advancing to non-human primate and human clinical studies for the development of HIV vaccines based on rBCG vectors.
Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, Ero J, Fabjan C, Friedl M, Fruhwirth R, Ghete VM, Hartl C, Hormann N, Hrubec J, Jeitler M, Kiesenhofer W, Knuenz V, Krammer M, Kratschmer I, Liko D, Mikulec I, Rabady D, Rahbaran B, Rohringer H, Schofbeck 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, DeWolf EA, Janssen X, Knutsson A, Luyckx S, Ochesanu S, Roland B, Rougny R, Van De Klundert M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Van Spilbeeck A, Blekman F, Blyweert S, D'Hondt J, Daci N, Heracleous N, Keaveney J, Lowette S, Maes M, Olbrechts A, Python Q, Strom D, Tavernier S, Van Doninck W, Van Mulders P, Van Onsem GP, Villella I, Caillol C, Clerbaux B, De Lentdecker G, Dobur D, Favart L, Gay APR, Grebenyuk A, Leonard A, Mohammadi A, Pernie L, Reis T, Seva T, Thomas L, Velde CV, Vanlaer P, Wang J, Adler V, Beernaert K, Benucci L, Cimmino A, Costantini S, Crucy S, Dildick S, Fagot A, Garcia G, Mccartin J, Rios AAO, Ryckbosch D, Diblen SS, Sigamani M, Strobbe N, Thyssen F, Tytgat M, Yazgan E, Zaganidis N, Basegmez S, Beluffi C, Bruno G, Castello R, Caudron A, Ceard L, Da Silveira GG, Delaere C, du Pree T, Favart D, Forthomme L, Giammanco A, Hollar J, Jez P, Komm M, Lemaitre V, Nuttens C, Pagano D, Perrini L, Pin A, Piotrzkowski K, Popov A, Quertenmont L, Selvaggi M, Marono MV, Garcia JMV, Beliy N, Caebergs T, Daubie E, Hammad GH, Alda WL, Alves GA, Brito L, Martins MC, Martins TDR, Pol ME, Carvalho W, Chinellato J, Custodio A, Da Costa EM, Damiao DD, Martins CD, De Souza SF, Malbouisson H, Figueiredo DM, Mundim L, Nogima H, Da Silva WLP, Santaolalla J, Santoro A, Sznajder A, Manganote EJT, Pereira AV, Bernardes CA, Tomei TRFP, Gregores EM, Mercadante PG, Novaes SF, Padula SS, Aleksandrov A, Genchev V, Iaydjiev P, Marinov A, Piperov S, Rodozov M, Sultanov G, Vutova M, Dimitrov A, Glushkov I, Hadjiiska R, Kozhuharov V, Litov L, Pavlov B, Petkov P, Bian JG, Chen GM, Chen HS, Chen M, Du R, Jiang CH, Liang D, Liang S, Plestina R, Tao J, Wang X, Wang Z, Asawatangtrakuldee C, Ban Y, Guo Y, Li Q, Li W, Liu S, Mao Y, Qian SJ, Wang D, Zhang L, Zou W, Avila C, 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, Mekterovic D, Sudic L, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Bodlak M, Finger M, Finger M, Assran Y, Kamel AE, Mahmoud MA, Radi A, Kadastik M, Murumaa M, Raidal M, 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, 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, Malcles J, Rander J, Rosowsky A, Titov M, Baffioni S, Beaudette F, Busson P, Charlot C, Dahms T, Dalchenko M, Dobrzynski L, Filipovic N, Florent A, de Cassagnac RG, Mastrolorenzo L, Mine P, Mironov C, Naranjo IN, Nguyen M, Ochando C, Paganini P, Salerno R, Sauvan JB, Sirois Y, Veelken C, Yilmaz Y, Zabi A, Agram JL, Andrea J, Aubin A, Bloch D, Brom JM, Chabert EC, Collard C, Conte E, Fontaine JC, Gele D, Goerlach U, Goetzmann C, Le Bihan AC, Van Hove P, Gadrat S, Beauceron S, Beaupere N, Boudoul G, Bouvier E, Brochet S, Montoya CAC, Chasserat J, Chierici R, Contardo D, Depasse P, El Mamouni H, Fan J, Fay J, Gascon S, Gouzevitch M, Ille B, Kurca T, Lethuillier M, Mirabito L, Perries S, Alvarez JDR, Sabes D, Sgandurra L, Sordini V, Donckt MV, Verdier P, Viret S, Xiao H, Tsamalaidze Z, Autermann C, Beranek S, Bontenackels M, Edelhoff M, Feld L, Hindrichs O, Klein K, Ostapchuk A, Perieanu A, Raupach F, Sammet J, Schael S, Weber H, Wittmer B, Zhukov V, Ata M, Dietz-Laursonn E, Duchardt D, Erdmann M, 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, Reithler H, Schmitz SA, Sonnenschein L, Teyssier D, Thuer S, Weber M, Cherepanov V, Erdogan Y, Flugge G, Geenen H, Geisler M, Ahmad WH, Hoehle F, Kargoll B, Kress T, Kuessel Y, Lingemann J, Nowack A, Nugent IM, Perchalla L, Pooth O, Stahl A, Asin I, Bartosik N, Behr J, Behrenhoff W, Behrens U, Bell AJ, Bergholz M, Bethani A, Borras K, Burgmeier A, Cakir A, Calligaris L, Campbell A, Choudhury S, Costanza F, Pardos CD, Dooling S, Dorland T, Eckerlin G, Eckstein D, Eichhorn T, Flucke G, Garcia JG, Geiser A, Gunnellini P, Hauk J, Hellwig G, Hempel M, Horton D, Jung H, Kalogeropoulos A, Kasemann M, Katsas P, Kieseler J, Kleinwort C, Krucker D, Lange W, Leonard J, Lipka K, Lobanov A, Lohmann W, Lutz B, Mankel R, Marfin I, Melzer-Pellmann IA, Meyer AB, Mnich J, Mussgiller A, Naumann-Emme S, Nayak A, Novgorodova O, Nowak F, Ntomari E, Perrey H, Pitzl D, Placakyte R, Raspereza A, Cipriano PMR, Ron E, Sahin MO, Salfeld-Nebgen J, Saxena P, Schmidt R, Schoerner-Sadenius T, Schroder M, Seitz C, Spannagel S, Trevino ADRV, Walsh R, Wissing C, Martin MA, Blobel V, Vignali MC, Draeger AR, Erfle J, Garutti E, Goebel K, Gorner M, Haller J, Hoffmann M, Hoing RS, Kirschenmann H, Klanner R, Kogler R, Lange J, Lapsien T, Lenz T, Marchesini I, Ott J, Peiffer T, Pietsch N, Pohlsen T, Rathjens D, Sander C, Schettler H, Schleper P, Schlieckau E, Schmidt A, Seidel M, Sibille J, Sola V, Stadie H, Steinbruck G, Troendle D, Usai E, Vanelderen L, Barth C, Baus C, Berger J, Boser C, Butz E, Chwalek T, De Boer W, Descroix A, Dierlamm A, Feindt M, Frensch F, Giffels M, Hartmann F, Hauth T, Husemann U, Katkov I, Kornmayer A, Kuznetsova E, Pardo PL, Mozer MU, Muller T, Nurnberg A, Quast G, Rabbertz K, Ratnikov F, Rocker S, Simonis HJ, Stober FM, Ulrich R, Wagner-Kuhr J, Wayand S, Weiler T, Wolf R, Anagnostou G, Daskalakis G, Geralis T, Giakoumopoulou VA, Kyriakis A, Loukas D, Markou A, Markou C, Psallidas A, Topsis-Giotis I, Panagiotou A, Saoulidou N, Stiliaris E, Aslanoglou X, Evangelou I, Flouris G, Foudas C, Kokkas P, Manthos N, Papadopou-Los I, Paradas E, Bencze G, Hajdu C, Hidas P, Horvath D, Sikler F, Veszpremi V, Vesztergombi G, Zsigmond AJ, Beni N, Czellar S, Karancsi J, Molnar J, Palinkas J, Szillasi Z, Raics P, Trocsanyi ZL, Ujvari B, Swain SK, Beri SB, Bhatnagar V, Dhingra N, Gupta R, Bhawandeep U, Kalsi AK, Kaur M, Mittal M, Nishu N, Singh JB, Kumar A, Kumar A, Ahuja S, Bhardwaj A, Choudhary BC, Kumar A, Malhotra S, Naimuddin M, Ranjan K, Sharma V, 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, Abdulsalam A, Dutta D, Kailas S, Kumar V, Mohanty AK, Pant LM, Shukla P, Topkar A, Aziz T, Banerjee S, Bhowmik S, Chatterjee RM, Dewanjee RK, Dugad S, Gan-Guly 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, Bakhshiansohi H, Behnamian H, Etesami SM, Fahim A, Goldouzian R, Jafari A, Khakzad M, Najafabadi MM, Naseri M, Mehdiabadi SP, Safarzadeh B, Zeinali M, Felcini M, Grunewald M, Abbrescia M, Barbone L, Calabria C, Chhibra SS, Colaleo A, Creanza D, De Filippis N, De Palma M, Fiore L, Iaselli G, Maggi G, Maggi M, My S, Nuzzo S, Pompili A, Pugliese G, Radogna R, 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, 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, Primavera F, Rossi AM, Rovelli T, Siroli GP, Tosi N, Travaglini R, Albergo S, Cappello G, Chiorboli M, Costa S, Giordano F, Potenza R, Tricomi A, Tuve C, Barbagli G, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Gallo E, Gonzi S, Gori V, Lenzi P, Meschini M, Paoletti S, Sguazzoni G, Tropiano A, Benussi L, Bianco S, Fabbri F, Piccolo D, Ferro F, Lo Vetere M, Robutti E, Tosi S, Dinardo ME, Fiorendi S, Gennai S, Gerosa R, Ghezzi A, Govoni P, Lucchini MT, Malvezzi S, Manzoni RA, Martelli A, Marzocchi B, Menasce D, Moroni L, Paganoni M, Pedrini D, Ragazzi S, Redaelli N, de Fatis TT, Buontempo S, Cavallo N, Di Guida S, Fabozzi F, Iorio AOM, Lista L, Meola S, Merola M, Paolucci P, Azzi P, Bacchetta N, Bisello D, Branca A, Carlin R, Checchia P, Dall'Osso M, Dorigo T, Dosselli U, Galanti M, 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, Ventura S, Zotto P, Zucchetta A, Zumerle G, Gabusi M, Ratti SP, Riccardi C, Salvini P, Vitulo P, Biasini M, Bilei GM, Ciangottini D, Fano L, Lariccia P, Mantovani G, Menichelli M, Romeo F, 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, Fiori F, Foa L, Giassi A, Grippo MT, Ligabue F, Lomtadze T, Martini L, Messineo A, Moon CS, Palla F, Rizzi A, Savoy-Navarro A, Serban AT, Spagnolo P, Squillacioti P, Tenchini R, Tonelli G, Venturi A, Verdini PG, Vernieri C, Barone L, Cavallari F, D'imperio G, Del Re D, Diemoz M, Grassi M, Jorda C, Longo E, Margaroli F, Meridiani P, Micheli F, Nourbakhsh S, Organtini G, Paramatti R, Rahatlou S, Rovelli C, Santanastasio F, Soffi L, Traczyk P, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Bellan R, Biino C, Cartiglia N, Casasso S, Costa M, Degano A, Demaria N, Finco L, Mariotti C, Maselli S, Migliore E, Monaco V, Musich M, Obertino MM, Ortona G, Pacher L, Pastrone N, Pelliccioni M, Angioni GLP, Potenza A, 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, Montanino D, Schizzi A, Umer T, Zanetti A, Chang S, Kropivnitskaya A, Nam SK, Kim DH, Kim GN, Kim MS, Kong DJ, Lee S, Oh YD, Park H, Sakharov A, Son DC, Kim TJ, Kim JY, Song S, Choi S, Gyun D, Hong B, Jo M, Kim H, Kim Y, Lee B, Lee KS, Park SK, Roh Y, Choi M, Kim JH, Park IC, Park S, Ryu G, Ryu MS, Choi Y, Choi YK, Goh J, Kim D, Kwon E, Lee J, Seo H, Yu I, Juodagalvis A, Komaragiri JR, Ali MABM, Castilla-Valdez H, De La Cruz-Burelo E, Heredia-de La Cruz I, Lopez-Fernandez R, Sanchez-Hernandez A, Moreno SC, Valencia FV, Pedraza I, Ibarguen HAS, Linares EC, Pineda AM, Krofcheck D, Butler PH, Reucroft S, Ahmad A, Ahmad M, Hassan Q, Hoorani HR, Khalid S, Khan WA, Khurshid T, Shah MA, 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, Cwiok M, Dominik W, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Olszewski M, Wolszczak W, Bargassa P, E Silva CBD, Faccioli P, Parracho PGF, Gallinaro M, Nguyen F, Antunes JR, Seixas J, 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Search for the associated production of the Higgs boson with a top-quark pair
JOURNAL OF HIGH ENERGY PHYSICS 2014 SEP 16; ?(9):? Article 087
A search for the standard model Higgs boson produced in association with a top-quark pair (t (t) over barH) is presented, using data samples corresponding to integrated luminosities of up to 5.1 fb(-1) and 19.7 fb(-1) collected in pp collisions at center-of-mass energies of 7 TeV and 8 TeV respectively. The search is based on the following signatures of the Higgs boson decay: H -> hadrons, H -> photons, and H -> leptons. The results are characterized by an observed t (t) over barH signal strength relative to the standard model cross section, mu = sigma/sigma(SM), under the assumption that the Higgs boson decays as expected in the standard model. The best fit value is mu = 2.8 +/- 1.0 for a Higgs boson mass of 125.6 GeV.
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Measurement of top quark-antiquark pair production in association with a W or Z boson in pp collisions at root s=8 TeV
EUROPEAN PHYSICAL JOURNAL C 2014 SEP 17; 74(9):? Article 3060
A measurement of the cross section for the production of top quark-antiquark pairs (t (t) over bar) in association with a vector boson V (W or Z) in proton-proton collisions at root s = 8 TeV is presented. The results are based on a dataset corresponding to an integrated luminosity of 19.5 fb(-1) recorded with the CMS detector at the LHC. The measurement is performed in three leptonic (e and mu) channels: a same-sign dilepton analysis targeting t (t) over barW events, and trilepton and four-lepton analyses designed for t (t) over barZ events. In the same-sign dilepton channel, the t (t) over barW cross section is measured as sigma(t (t) over barW) = 170(-80)(+90) (stat) +/- 70 (syst) fb, corresponding to a significance of 1.6 standard deviations over the background-only hypothesis. Combining the trilepton and four-lepton channels, a direct measurement of the t (t) over barZ cross section, sigma(t (t) over barZ) = 200(-70)(+80) (stat)(-30)(+40) (syst)fb(-1), is obtained with a significance of 3.1 standard deviations. The measured cross sections are compatible with standard model predictions within their experimental uncertainties. The inclusive t (t) over barV process is observed with a significance of 3.7 standard deviations from the combination of all three leptonic channels.
Gao P, Zillinger T, Wang WY, Ascano M, Dai PH, Hartmann G, Tuschl T, Deng L, Barchet W, Patel DJ
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Binding-Pocket and Lid-Region Substitutions Render Human STING Sensitive to the Species-Specific Drug DMXAA
CELL REPORTS 2014 SEP 25; 8(6):1668-1676
The drug DMXAA (5,6-dimethylxanthenone-4-acetic acid) showed therapeutic promise against solid tumors in mouse models but subsequently failed in human clinical trials. DMXAA was later discovered to activate mouse, but not human, STING, an adaptor protein in the cyclic dinucleotide cGAMP-mediated signaling pathway, inducing type I interferon expression. To facilitate the development of compounds that target human STING, we combined structural, biophysical, and cellular assays to study mouse and human chimeric proteins and their interaction with DMXAA. We identified a single substitution (G230I) that enables a DMXAA-induced conformational transition of hSTING from an inactive "open" to an active "closed" state. We also identified a substitution within the binding pocket (Q266I) that cooperates with G230I and the previously identified S162A binding-pocket point substitution, rendering hSTING highly sensitive to DMXAA. These findings should facilitate the reciprocal engineering of DMXAA analogs that bind and stimulate wild-type hSTING and their exploitation for vaccine-adjuvant and anticancer drug development.
Budde PP
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So you think you can edit?
MOLECULAR BIOLOGY OF THE CELL 2014 SEP 1; 25(17):2539-2541
This article presents one scientist's perspective on the transition from life at the bench to an editorial career.