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Macro L, Jaiswal JK, Simon SM
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Dynamics of clathrin-mediated endocytosis and its requirement for organelle biogenesis in Dictyostelium
JOURNAL OF CELL SCIENCE 2012 DEC 1; 125(23):5721-5732
The protein clathrin mediates one of the major pathways of endocytosis from the extracellular milieu and plasma membrane. In single-cell eukaryotes, such as Saccharomyces cerevisiae, the gene encoding clathrin is not an essential gene, raising the question of whether clathrin conveys specific advantages for multicellularity. Furthermore, in contrast to mammalian cells, endocytosis in S. cerevisiae is not dependent on either clathrin or adaptor protein 2 (AP2), an endocytic adaptor molecule. In this study, we investigated the requirement for components of clathrin-mediated endocytosis (CME) in another unicellular organism, the amoeba Dictyostelium. We identified a heterotetrameric AP2 complex in Dictyostelium that is similar to that which is found in higher eukaryotes. By simultaneously imaging fluorescently tagged clathrin and AP2, we found that, similar to higher eukaryotes, these proteins colocalized to membrane puncta that move into the cell together. In addition, the !
Singer S, Zhao RY, Barsotti AM, Ouwehand A, Fazollahi M, Coutavas E, Breuhahn K, Neumann O, Longerich T, Pusterla T, Powers MA, Giles KM, Leedman PJ, Hess J, Grunwald D, Bussemaker HJ, Singer RH, Schirmacher P, Prives C
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Nuclear Pore Component Nup98 Is a Potential Tumor Suppressor and Regulates Posttranscriptional Expression of Select p53 Target Genes
MOLECULAR CELL 2012 DEC 14; 48(5):799-810
The p53 tumor suppressor utilizes multiple mechanisms to selectively regulate its myriad target genes, which in turn mediate diverse cellular processes. Here, using conventional and single-molecule mRNA analyses, we demonstrate that the nucleoporin Nup98 is required for full expression of p21, a key effector of the p53 pathway, but not several other p53 target genes. Nup98 regulates p21 mRNA levels by a posttranscriptional mechanism in which a complex containing Nup98 and the p21 mRNA 3'UTR protects p21 mRNA from degradation by the exosome. An in silico approach revealed another p53 target (14-3-3 sigma) to be similarly regulated by Nup98. The expression of Nup98 is reduced in murine and human hepatocellular carcinomas (HCCs) and correlates with p21 expression in HCC patients. Our study elucidates a previously unrecognized function of wild-type Nup98 in regulating select p53 target genes that is distinct from the well-characterized oncogenic properties of Nup98 fusion proteins.
Simon DJ, Weimer RM, McLaughlin T, Kallop D, Stanger K, Yang J, O'Leary DDM, Hannoush RN, Tessier-Lavigne M
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A Caspase Cascade Regulating Developmental Axon Degeneration
JOURNAL OF NEUROSCIENCE 2012 DEC 5; 32(49):17540-17553
Axon degeneration initiated by trophic factor withdrawal shares many features with programmed cell death, but many prior studies discounted a role for caspases in this process, particularly Caspase-3. Recently, Caspase-6 was implicated based on pharmacological and knockdown evidence, and we report here that genetic deletion of Caspase-6 indeed provides partial protection from degeneration. However, we find at a biochemical level that Caspase-6 is activated effectively only by Caspase-3 but not other "upstream" caspases, prompting us to revisit the role of Caspase-3. In vitro, we show that genetic deletion of Caspase-3 is fully protective against sensory axon degeneration initiated by trophic factor withdrawal, but not injury-induced Wallerian degeneration, and we define a biochemical cascade from prosurvival Bcl2 family regulators to Caspase-9, then Caspase-3, and then Caspase-6. Only low levels of active Caspase-3 appear to be required, helping explain why its critical role has been obscured in prior studies. In vivo, Caspase-3 and Caspase-6-knockout mice show a delay in developmental pruning of retinocollicular axons, thereby implicating both Caspase-3 and Caspase-6 in axon degeneration that occurs as a part of normal development.
Gittler JK, Shemer A, Suarez-Farinas M, Fuentes-Duculan J, Gulewicz KJ, Wang CQF, Mitsui H, Cardinale I, Strong CD, Krueger JG, Guttman-Yassky E
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Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 2012 DEC; 130(6):1344-1354
Background: Atopic dermatitis (AD) is a common disease with an increasing prevalence. The primary pathogenesis of the disease is still elusive, resulting in the lack of specific treatments. AD is currently considered a biphasic disease, with T(H)2 predominating in acute disease and a switch to T(H)1 characterizing chronic disease. Elucidation of the molecular factors that participate in the onset of new lesions and maintenance of chronic disease is critical for the development of targeted therapeutics. Objectives: We sought to characterize the mechanisms underlying the onset and maintenance of AD. Methods: We investigated intrapersonal sets of transcriptomes from nonlesional skin and acute and chronic lesions of 10 patients with AD through genomic, molecular, and cellular profiling. Results: Our study associated the onset of acute lesions with a striking increase in a subset of terminal differentiation proteins, specifically the cytokine-modulated S100A7, S100A8, and S100A9. Acute disease was also associated with significant increases in gene expression levels of major T(H)22 and T(H)2 cytokines and smaller increases in IL-17 levels. A lesser induction of T(H)1-associated genes was detected in acute disease, although some were significantly upregulated in chronic disease. Further significant intensification of major T(H)22 and T(H)2 cytokines was observed between acute and chronic lesions. Conclusions: Our data identified increased S100A7, S100A8, and S100A9 gene expression with AD initiation and concomitant activation of T(H)2 and T(H)22 cytokines. Our findings support a model of progressive activation of T(H)2 and T(H)22 immune axes from the acute to chronic phases, expanding the prevailing view of pathogenesis with important therapeutic implications. (J Allergy Clin Immunol 2012;130:1344-54.)
Valente C, De Lencastre H, Sa-Leao R
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Pherotypes of Co-Colonizing Pneumococci Among Portuguese Children
MICROBIAL DRUG RESISTANCE 2012 DEC; 18(6):550-554
A recent study showed that pneumococcal pherotypes often coexist in the nasopharynx and suggested that the impact of pherotype-mediated fratricide on competition is limited. We determined the impact of pherotype (or competence-stimulating peptide [CSP]) on pneumococcal nasopharyngeal co-colonization. Of 184 nasopharyngeal samples yielding two serotypes, 39.9% contained CSP1 only, 12.6% CSP2 only, and 47.5% had one strain of each pherotype. The observed proportions of concordant and discordant pherotypes (52.5% and 47.5%, respectively), were compared with the ones estimated (53.8% and 46.2%, respectively), and there were no significant differences (p = 0.9, chi(2) test). Our results support the hypothesis that there is a limited role of pherotype in co-colonization.
Huang YM, Merkatz R, Kang JZ, Roberts K, Hu XY, Di Donato F, Sitruk-Ware R, Cheng LN
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Postpartum unintended pregnancy and contraception practice among rural-to-urban migrant women in Shanghai
CONTRACEPTION 2012 DEC; 86(6):731-738
Background: Rural-to-urban migrant women in Shanghai have poor reproductive health; the incidence of postpartum unintended pregnancy and contraceptive practices has not been adequately studied in this population. Study Design: This retrospective study examined the incidence of postpartum unintended pregnancy and associated factors among migrant women and included a medical records reviews, telephone interviews and in-depth face-to-face interviews. Results: The incidence of unintended pregnancy during the first and second years postpartum was 12.8 and 12.9 per 100 women-years, respectively. Eighty-six percent resulted from nonuse of contraception, and 88% ended in induced abortions. Median times of sexual activity resumption and contraception initiation were 2 months and 7.5 months postpartum, respectively. Approximately 17% of women did not adopt effective contraceptive methods until undergoing induced abortion. Conclusions: Concentrated efforts, including contraception counseling prior to discharge and early postpartum visits, are required to increase early use of effective contraception among rural-to-urban migrant women in Shanghai and to reduce their high level of postpartum unintended pregnancy. (C) 2012 Elsevier Inc. All rights reserved.
Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Aguilo E, Bergauer T, Dragicevic M, Ero J, Fabjan C, Friedl M, Fruhwirth R, Ghete VM, Hammer J, Hormann N, Hrubec J, Jeitler M, Kiesenhofer W, Knunz V, Krammer M, Kratschmer I, Liko D, Mikulec I, Pernicka M, Rahbaran B, Rohringer C, Rohringer H, Schofbeck R, Strauss J, Taurok A, Waltenberger W, Walzel G, Widl E, Wulz CE, Mossolov V, Shumeiko N, Gonzalez JS, Bansal M, Bansal S, Cornelis T, De Wolf EA, Janssen X, Luyckx S, Mucibello L, Ochesanu S, Roland B, Rougny R, Selvaggi M, Staykova Z, Van Haevermaet H, Van Mechelen P, Van Remortel N, Van Spilbeeck A, Blekman F, Blyweert S, D'Hondt J, Suarez RG, Kalogeropoulos A, Maes M, Olbrechts A, Van Doninck W, Van Mulders R, Van Onsem GP, Villella I, Clerbaux B, De Lentdecker G, Dero V, Gay APR, Hreus T, Leonard A, Marage PE, Mohammadi A, Reis T, Thomas L, Vander Marcken G, Vander Velde C, Vanlaer P, Wang J, Adler V, Beernaert K, Cimmino A, Costantini S, Garcia G, Grunewald M, Klein B, Lellouch J, Marinov A, Mccartin J, Rios AAO, Ryckbosch D, Strobbe N, Thyssen F, Tytgat M, Verwilligen P, Walsh S, Yazgan E, Zaganidis N, Basegmez S, Bruno G, Castello R, Ceard L, Delaere C, du Pree T, Favart D, Forthomme L, Giammanco A, Hollar J, Lemaitre V, Liao J, Militaru O, Nuttens C, Pagano D, Pin A, Piotrzkowski K, Schul N, Garcia JMV, Beliy N, Caebergs T, Daubie E, Hammad GH, Alves GA, Martins MC, Damiao DD, Martins T, Pol ME, Souza MHG, Alda WL, Carvalho W, Custodio A, Da Costa EM, Martins CD, De Souza SF, Figueiredo DM, Mundim L, Nogima H, Oguri V, Da Silva WLP, Santoro A, Jorge LS, Sznajder A, Anjos TS, Bernardes CA, Dias FA, Tomei TRFP, Gregores EM, Lagana C, Marinho F, Mercadante PG, Novaes SF, Padula SS, Genchev V, Iaydjiev P, Piperov S, Rodozov M, Stoykova S, Sultanov G, Tcholakov V, Trayanov R, 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, Zang J, Zhang Z, Asawatangtrakuldee C, Ban Y, Guo Y, Li W, Liu S, Mao Y, Qian SJ, Teng H, Wang D, Zhang L, Zou W, Avila C, Gomez JP, Moreno BG, Oliveros AFO, Sanabria JC, Godinovic N, Lelas D, Plestina R, Polic D, Puljak I, Antunovic Z, Kovac M, Brigljevic V, Duric S, Kadija K, Luetic J, Morovic S, Attikis A, Galanti M, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Finger M, Finger M, Assran Y, Elgammal S, Kamel AE, Khalil S, Mahmoud MA, Radi A, Kadastik M, Muntel M, Raidal M, Rebane L, Tiko A, Eerola P, Fedi G, Voutilainen M, Harkonen J, Heikkinen A, 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, Ungaro D, Wendland L, Banzuzi K, Karjalainen A, Korpela A, Tuuva T, Besancon M, Choudhury S, 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, Shreyber I, Titov M, Baffioni S, Beaudette F, Benhabib L, Bianchini L, Bluj M, Broutin C, Busson P, Charlot C, Daci N, Dahms T, Dalchenko M, Dobrzynski L, 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, Cardaci M, Chabert EC, Collard C, Conte E, Drouhin F, Ferro C, Fontaine JC, Gele D, Goerlach U, Juillot P, Le Bihan AC, Van Hove P, Fassi F, Mercier D, Beauceron S, Beaupere N, Bondu O, Boudoul G, Chasserat J, Chierici R, Contardo D, Depasse P, El Mamouni H, Fay J, Gascon S, Gouzevitch M, Ille B, Kurca T, Lethuillier M, Mirabito L, Perries S, Sgandurra L, Sordini V, Tschudi Y, Verdier P, Viret S, Tsamalaidze Z, Anagnostou G, Autermann C, Beranek S, Edelhoff M, Feld L, Heracleous N, Hindrichs O, Jussen R, Klein K, Merz J, 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, Papacz P, Pieta H, Reithler H, Schmitz SA, Sonnenschein L, Steggemann J, Teyssier D, Weber M, Bontenackels 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, Perchalla L, Pooth O, Sauerland P, Stahl A, Martin MA, Behr J, Behrenhoff W, Behrens U, Bergholz M, Bethani A, Borras K, Burgmeier A, Cakir A, Calligaris L, Campbell A, Castro E, Costanza E, Dammann D, Pardos CD, 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, Knutsson A, Kramer M, Krucker D, Kuznetsova E, Lange W, Lohmann W, Lutz B, Mankel R, Marfin I, Marienfeld M, Melzer-Pellmann IA, Meyer AB, Mnich J, Mussgiller A, Naumann-Emme S, Novgorodova O, Olzem J, Perrey H, Petrukhin A, Pitzl D, Raspereza A, Cipriano PMR, Riedl C, Ron E, Rosin M, Salfeld-Nebgen J, Schmidt R, Schoerner-Sadenius T, Sen N, Spiridonov A, Stein M, Walsh R, Wissing C, Blobel V, Draeger J, Enderle H, Erfle J, Gebbert U, Gorner M, Hermanns T, Hoing RS, Kaschube K, Kaussen G, Kirschenmann H, Klanner R, Lange J, Mura B, Nowak F, Peiffer T, Pietsch N, Rathjens D, Sander C, Schettler H, Schleper P, Schlieckau E, Schmidt A, Schroder M, Schum T, Seidel M, Sola V, Stadie H, Steinbruck G, Thomsen J, Vanelderen L, Barth C, Berger J, Boser C, Chwalek T, De Boer W, Descroix A, Dierlamm A, Feindt M, Guthoff M, Hackstein C, Hartmann F, Hauth T, Heinrich M, Held H, Hoffmann KH, Husemann U, Katkov I, Komaragiri JR, Pardo PL, Martschei D, Mueller S, Muller T, Niegel M, Nurnberg A, Oberst O, Oehler A, Ott J, Quast G, Rabbertz K, Ratnikov F, Ratnikova N, Rocker S, Schilling FP, Schott G, Simonis HJ, Stober FM, Troendle D, Ulrich R, Wagner-Kuhr J, Wayand S, Weiler T, Zeise M, Daskalakis G, Geralis T, Kesisoglou S, Kyriakis A, Loukas D, Manolakos I, Markou A, Markou C, Mavrommatis C, Ntomari E, Gouskos L, Mertzimekis TJ, Panagiotou A, Saoulidou N, Evangelou I, Foudas C, Kokkas P, Manthos N, Papadopoulos I, Patras V, Bencze G, Hajdu C, Hidas P, Horvath D, Sikler F, Veszpremi V, Vesztergombi G, Beni N, Czellar S, Molnar J, Palinkas J, Szillasi Z, Karancsi J, Raics P, Trocsanyi ZL, Ujvari B, Beri SB, Bhatnagar V, Dhingra N, Gupta R, Kaur M, Mehta MZ, Nishu N, Saini LK, Sharma A, Singh JB, Kumar A, Kumar A, Ahuja S, Bhardwaj A, Choudhary BC, Malhotra S, Naimuddin M, Ranjan K, Sharma V, Shivpuri RK, Banerjee S, Bhattacharya S, Dutta S, Gomber B, Jain S, Jain S, Khurana R, Sarkar S, Sharan M, Abdulsalam A, Choudhury RK, Dutta D, Kailas S, Kumar V, Mehta P, Mohanty AK, Pant LM, Shukla P, Aziz T, Ganguly S, Guchait M, 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, Hashemi M, Hesari H, Jafari A, Khakzad M, Najafabadi MM, Mehdiabadi SP, Safarzadeh B, Zeinali M, Abbrescia M, Barbone L, Calabria C, Chhibra SS, Colaleo A, Creanza D, De Filippis N, De Palma M, Fiore L, Iaselli G, Lusito L, Maggi G, Maggi M, Marangelli B, My S, Nuzzo S, Pacifico N, Pompili A, Pugliese G, Selvaggi G, Silvestris L, Singh G, Venditti R, Zito G, Abbiendi G, Benvenuti AC, Bonacorsi D, Braibant-Giacomelli S, Brigliadori L, Capiluppi P, Castro A, Cavallo FR, Cuffiani M, Dallavalle GM, Fabbri F, Fanfani A, Fasanella D, Giacomelli P, Grandi C, Guiducci L, Marcellini S, Masetti G, Meneghelli M, Montanari A, Navarria FL, Odorici E, Perrotta A, Primavera F, Rossi AM, Rovelli T, Siroli GP, Travaglini R, Albergo S, Cappello G, Chiorboli M, Costa S, Potenza R, Tricomi A, Tuve C, Barbagli G, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Frosali S, Gallo E, Gonzi S, Meschini M, Paoletti S, Sguazzoni G, Tropiano A, Benussi L, Bianco S, Colafranceschi S, Fabbri F, Piccolo D, Fabbricatore P, Musenich R, Tosi S, Benaglia A, De Guio F, Di Matteo L, Fiorendi S, Gennai S, Ghezzi A, Malvezzi S, Manzoni RA, Martelli A, Massironi A, Menasce D, Moroni L, Paganoni M, Pedrini D, Ragazzi S, Redaelli N, Sala S, de Fatis TT, Buontempo S, Montoya CAC, Cavallo N, De Cosa A, Dogangun O, Fabozzi F, Iorio AOM, Lista L, Meola S, Merola M, Paolucci P, Azzi P, Bacchettaa N, Bellan P, Biggio C, Bisello D, Bonnet F, Branca A, Carlin R, Checchia P, Dorigo T, Gasparini F, Gozzelino A, Kanishchev K, Lacaprara S, Lazzizzera I, Margoni M, Meneguzzo AT, Nespolo M, Pazzini J, Pozzobon N, Ronchese P, Simonetto F, Torassa E, Tosi M, Vanini S, Zotto P, Zumerle G, Gabusi M, Ratti SP, Riccardi C, Torre P, Vitulo P, Biasini M, Bilei GM, Fano L, Lariccia P, Mantovani G, Menichelli M, Nappi A, Romeo F, Saha A, Santocchia A, Spiezia A, Taroni S, Azzurri P, Bagliesi G, Bernardini J, Boccali T, Broccolo G, Castaldia R, D'Agnolo RT, Dell'Orso R, Fiori F, Foa L, Giassi A, 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, Barone L, Cavallari F, Del Re D, Diemoz M, Fanelli C, Grassi M, Longo E, Meridiani P, Micheli F, Nourbakhsh S, Organtini G, Paramatti R, Rahatlou S, Sigamani M, Soffi L, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Biino C, Cartiglia N, Costa M, Demaria N, Mariotti C, Maselli S, Migliore E, Monaco V, Musich M, Obertino MM, Pastrone N, Pelliccioni M, Potenza A, Romero A, Ruspa M, Sacchi R, Solano A, Staiano A, Pereira AV, Belforte S, Candelise V, Casarsa M, Cossutti F, Della Ricca G, Gobbo B, Marone M, Montanino D, Penzo A, Schizzi A, Heo SG, Kim TY, Nam SK, Chang S, Kim DH, Kim GN, Kong DJ, Park H, Ro SR, Son DC, Son T, Kim JY, Kim ZJ, Song S, Choi S, Gyun D, Hong B, Jo M, Kim H, Kim TJ, Lee KS, Moon DH, Park SK, Choi M, Kim JH, Park C, Park IC, Park S, Ryu G, Cho Y, Choi Y, Choi YK, Goh J, Kim MS, Kwon E, Lee B, Lee J, Lee S, Seo H, Yu I, Bilinskas MJ, Grigelionis I, Janulis M, Juodagalvis A, Castilla-Valdez H, De La Cruz-Burelo E, Heredia-de La Cruz I, Lopez-Fernandez R, Villalba RM, Martinez-Ortega J, Sanchez-Hernandez A, Villasenor-Cendejas LM, Moreno SC, Valencia FV, Ibarguen HAS, Linares EC, Pineda AM, Reyes-Santos MA, Krofcheck D, Bell AJ, Butler PH, Doesburg R, Reucroft S, Silverwood H, Ahmad M, Ansari MH, Asghar MI, Hoorani HR, Khalid S, Khan WA, Khurshid T, Qazi S, Shah MA, Shoaib M, Bialkowska H, Boimska B, Frueboes T, Gokieli R, 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, Almeida N, Bargassa P, David A, Faccioli P, Parracho PCF, Gallinaro M, Seixas J, Varela J, Vischia P, Belotelov I, Bunin P, Gavrilenko M, Golutvin I, Gorbunov I, Kamenev A, Karjavin V, Kozlov G, Lanev A, Malakhov A, Moisenz P, Palichik V, Perelygin V, Shmatov S, Smirnov V, Volodko A, 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, Matveev V, Pashenkov A, Tlisov D, Toropin A, Epshteyn V, Erofeeva M, Gavrilov V, Kossov M, Lychkovskaya N, Popov V, Safronov G, Semenov S, Stolin V, Vlasov E, Zhokin A, Belyaev A, Boos E, Dubinin M, Dudko L, Ershov A, Gribushin A, Klyukhin V, Kodolova O, Lokhtin I, Markina A, Obraztsov S, Perfilov M, Petrushanko S, Popov A, Sarycheva L, Savrin V, Snigirev A, Andreev V, Azarkin M, Dremin I, Kirakosyan M, Leonidov A, Mesyats G, Rusakov SV, Vinogradov A, Azhgirey I, Bayshev I, Bitioukov S, Grishin V, Kachanov V, 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, Maestre JA, Arce P, Battilana C, Calvo E, Cerrada M, Llatas MC, Colino N, De La Cruz 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, Pelayo JP, Olmeda AQ, Redondo I, Romero L, Santaolalla J, Soares MS, Willmott C, Albajar C, Codispoti G, de Troconiz JF, Brun H, Cuevas J, Menendez JF, Folgueras S, Caballero IG, Iglesias LL, Gomez JP, Cifuentes JAB, Cabrillo IJ, Calderon A, Chuang SH, Campderros JD, Felcini M, Fernandez M, Gomez G, Sanchez JG, Graziano A, Jorda C, Virto AL, Marco J, Marco R, Rivero CM, Matorras F, Sanchez FJM, Rodrigo T, Rodriguez-Marrero AY, Ruiz-Jimeno A, Scodellaro L, Vila I, Cortabitarte RV, Abbaneo D, Auffray E, Auzinger G, Bachtis M, Baillon P, Ball AH, Barney D, Benitez JF, Bernet C, Bianchi G, Bloch P, Bocci A, Bonato A, Botta C, Breuker H, Camporesi T, Cerminara G, Christiansen T, Perez JAC, D'Enterria D, Dabrowski A, De Roeck A, Di Guida S, Dobson M, Dupont-Sagorin N, Elliott-Peisert A, Frisch B, Funk W, Georgiou G, Giffels M, Gigi D, Gill K, Giordano D, Girone M, Giunta M, Glege F, Garrido RGR, Govoni P, Gowdy S, Guida R, Hansen M, Harris P, Hartl C, Harvey J, Hegner B, Hinzmann A, Innocente V, Janot P, Kaadze K, Karavakis E, Kousouris K, Lecoq P, Lee YJ, Lenzi P, Lourenco C, Magini N, Maki T, Malberti M, Malgeri L, Mannelli M, Masetti L, Meijers F, Mersi S, Meschi E, Moser R, Mozer MU, Mulders M, Musella P, Nesvold E, Orimoto T, Orsini L, Cortezon EP, Perez E, Perrozzi L, Petrilli A, Pfeiffer A, Pierini M, Pimia M, Piparo D, Polese G, Quertenmont L, Racz A, Reece W, Antunes JR, 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, 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, Meier F, Renker D, Rohe T, Sibille J, Bani L, Bortignon P, Buchmann MA, Casal B, Chanon N, Deisher A, Dissertori G, Dittmar M, Donega M, Dunser M, Eugster J, Freudenreich K, 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Carlsmith D, Cepeda M, Dasu S, Friis E, Gray L, Grogg KS, Grothe M, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Klukas J, Lanaro A, Lazaridis C, Leonard J, Loveless R, Mohapatra A, Ojalvo I, Palmonari F, Pierro GA, Ross I, Savin A, Smith WH, Swanson J
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Search for heavy lepton partners of neutrinos in proton-proton collisions in the context of the type III seesaw mechanism
PHYSICS LETTERS B 2012 DEC 5; 718(2):348-368
A search is presented in proton-proton collisions at root s = 7 TeV for fermionic triplet states expected in type Ill seesaw models. The search is performed using final states with three isolated charged leptons and an imbalance in transverse momentum. The data, collected with the CMS detector at the LHC, correspond to an integrated luminosity of 4.9 fb(-1). No excess of events is observed above the background predicted by the standard model, and the results are interpreted in terms of limits on production cross sections and masses of the heavy partners of the neutrinos in type Ill seesaw models. Depending on the considered scenarios, lower limits are obtained on the mass of the heavy partner of the neutrino that range from 180 to 210 GeV. These are the first limits on the production of type III seesaw fermionic triplet states reported by an experiment at the LHC. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved.
Gonzalez AD, Wang G, Waters EM, Gonzales KL, Speth RC, Van Kempen TA, Marques-Lopes J, Young CN, Butler SD, Davisson RL, Iadecola C, Pickel VM, Pierce JP, Milner TA
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DISTRIBUTION OF ANGIOTENSIN TYPE 1A RECEPTOR-CONTAINING CELLS IN THE BRAINS OF BACTERIAL ARTIFICIAL CHROMOSOME TRANSGENIC MICE
NEUROSCIENCE 2012 DEC 13; 226(?):489-509
In the central nervous system, angiotensin II (AngII) binds to angiotensin type 1 receptors (AT(1)Rs) to affect autonomic and endocrine functions as well as learning and memory. However, understanding the function of cells containing AT(1)Rs has been restricted by limited availability of specific antisera, difficulties discriminating AT(1)R-immunoreactive cells in many brain regions and, the identification of AT(1)R-containing neurons for physiological and molecular studies. Here, we demonstrate that an Agtr1a bacterial artificial chromosome (BAC) transgenic mouse line that expresses type A AT(1)Rs (AT1aRs) identified by enhanced green fluorescent protein (EGFP) overcomes these shortcomings. Throughout the brain, AT1aR-EGFP was detected in the nuclei and cytoplasm of cells, most of which were neurons. EGFP often extended into dendritic processes and could be identified either natively or with immunolabeling of GFP. The distribution of AT1aR-EGFP cells in brain closely corresponded to that reported for AngII binding and AT1aR protein and mRNA. In particular, AT1aR-EGFP cells were in autonomic regions (e.g., hypothalamic paraventricular nucleus, central nucleus of the amygdala, parabrachial nucleus, nuclei of the solitary tract and rostral ventrolateral medulla) and in regions involved in electrolyte and fluid balance (i.e., subfornical organ) and learning and memory (i.e., cerebral cortex and hippocampus). Additionally, dual label electron microscopic studies in select brain areas demonstrate that cells containing AT1aR-EGFP colocalize with AT(1)R-immunoreactivity. Assessment of AngII-induced free radical production in isolated EGFP cells demonstrated feasibility of studies investigating AT1aR signaling ex vivo. These findings support the utility of Agtr1a BAC transgenic reporter mice for future studies understanding the role of AT(1)R-containing cells in brain function. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
Sather DN, Carbonetti S, Kehayia J, Kraft Z, Mikell I, Scheid JF, Klein F, Stamatatos L
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Broadly Neutralizing Antibodies Developed by an HIV-Positive Elite Neutralizer Exact a Replication Fitness Cost on the Contemporaneous Virus
JOURNAL OF VIROLOGY 2012 DEC; 86(23):12676-12685
Approximately 1% of those infected with HIV-1 develop broad and potent serum cross-neutralizing antibody activities. It is unknown whether or not the development of such immune responses affects the replication of the contemporaneous autologous virus. Here, we defined a pathway of autologous viral escape from contemporaneous potent and broad serum neutralizing antibodies developed by an elite HIV-1-positive (HIV-1(+)) neutralizer. These antibodies potently neutralize diverse isolates from different clades and target primarily the CD4-binding site (CD4-BS) of the viral envelope glycoprotein. Viral escape required mutations in the viral envelope glycoprotein which limited the accessibility of the CD4-binding site to the autologous broadly neutralizing anti-CD4-BS antibodies but which allowed the virus to infect cells by utilizing CD4 receptors on their surface. The acquisition of neutralization resistance, however, resulted in reduced cell entry potential and slower viral replication kinetics. Our results indicate that in vivo escape from autologous broadly neutralizing antibodies exacts fitness costs to HIV-1.
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Measurement of the single-top-quark t-channel cross section in pp collisions at root s=7 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2012 DEC; ?(12):? Article 035
A measurement of the single-top-quark t-channel production cross section in pp collisions at root s = 7TeV with the CMS detector at the LHC is presented. Two different and complementary approaches have been followed. The first approach exploits the distributions of the pseudorapidity of the recoil jet and reconstructed top-quark mass using background estimates determined from control samples in data. The second approach is based on multivariate analysis techniques that probe the compatibility of the candidate events with the signal. Data have been collected for the muon and electron final states, corresponding to integrated luminosities of 1.17 and 1.56 fb(-1), respectively. The single-top-quark production cross section in the t-channel is measured to be 67.2 +/- 6.1 pb, in agreement with the approximate next-to-next-to-leading-order standard model prediction. Using the standard model electroweak couplings, the CKM matrix element vertical bar V-tb vertical bar is measured!