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Mazo G, Soplop N, Wang WJ, Uryu K, Tsou MFB
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Spatial Control of Primary Ciliogenesis by subdistal Appendages Alters Sensation-Associated Properties of Cilia
DEVELOPMENTAL CELL 2016 NOV 21; 39(4):424-437
Vertebrate cells can initiate ciliogenesis from centrioles at the cell center, near the Golgi, forming primary cilia confined or submerged in a deep narrow pit created by membrane invagination. How or why cells maintain submerged cilia is unclear. Here, by characterizing centriole subdistal appendages (sDAP) in cells exclusively growing submerged cilia, we found that a group of sDAP components localize to the centriole proximal end through the cohesion factor C-Napl and that sDAP function redundantly with C-Napl for submerged cilia maintenance. Loss of sDAP and C-Napl has no effect on cilia assembly, but it disrupts stable Golgi-cilia association and allows normally submerged cilia to fully surface, losing the deep membrane invagination. Intriguingly, unlike submerged cilia (stationary), surfaced cilia actively respond to mechanical stimuli with motions and can ectopically recruit Hedgehog signaling components in the absence of agonist. We propose that spatial control of ciliogenesis uncouples or specifies sensory properties of cilia.
Wang XL, Li MMH, Zhao J, Li SL, MacDonald MR, Rice CM, Gao X, Gao GX
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Sindbis Virus Can Exploit a Host Antiviral Protein To Evade Immune Surveillance
JOURNAL OF VIROLOGY 2016 NOV; 90(22):10247-10258
Viral infection induces production of type I interferons (IFNs), which stimulate the expression of a variety of antiviral factors to inhibit viral replication. To establish effective infection, viruses need to develop strategies to evade the immune responses. A neurovirulent Sindbis virus strain with neuroinvasive properties (SVNI) causes lethal encephalitis in mice, and its replication in cultured cells is inhibited by the zinc finger antiviral protein (ZAP), a host factor that specifically inhibits the replication of certain viruses by binding to the viral mRNAs, repressing the translation of target mRNA, and promoting the degradation of target mRNA. We report here that murine embryonic fibroblast cells from ZAP knockout mice supported more efficient SVNI replication than wild-type cells. SVNI infection of 10-day-old suckling mice led to reduced survival in the knockout mice. Unexpectedly, however, SVNI infection of 23-day-old weanling mice, whose immune system is more developed than that of the suckling mice, resulted in significantly improved survival in ZAP knockout mice. Further analyses revealed that in the weanling knockout mice, SVNI replicated more efficiently in lymphoid tissues at early times postinfection and induced higher levels of IFN production, which restricted viral spread to the central nervous system. Blocking IFN activity through the use of receptor-neutralizing antibodies rendered knockout mice more sensitive to SVNI infection than wild-type mice. These results uncover a mechanism by which SVNI exploits a host antiviral factor to evade innate immune surveillance. IMPORTANCE Sindbis virus, a prototypic member of the Alphavirus genus, has been used to study the pathogenesis of acute viral encephalitis in mice for many years. How the virus evades immune surveillance to establish effective infection is largely unknown. ZAP is a host antiviral factor that potently inhibits Sindbis virus replication in cell culture. We show here that infection of ZAP knockout suckling mice with an SVNI led to faster disease progression. However, SVNI infection of weanling mice led to slower disease progression in knockout mice. Further analyses revealed that in weanling knockout mice, SVNI replicated more efficiently in lymphoid tissues at early times postinfection and induced higher levels of interferon production, which restricted viral spread to the central nervous system. These results uncover a mechanism by which SVNI exploits a host antiviral factor to evade innate immune surveillance and allow enhanced neuroinvasion.
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Reis T, Seva T, Thomas L, Velde CV, Vanlaer P, Wang J, Zenoni F, Beernaert K, Benucci L, Cimmino A, Crucy S, Fagot A, Garcia G, Gul M, Mccartin J, Rios AAO, Poyraz D, Ryckbosch D, Diblen SS, Sigamani M, Strobbe N, Thyssen F, Tytgat M, Van Driessche W, Yazgan E, Zaganidis N, Basegmez S, Beluffi C, Bondu O, Bruno G, Castello R, Caudron A, Ceard L, Da Silveira GG, Delaere C, du Pree T, Favart D, Forthomme L, Giammanco A, Hollar J, Jafari A, Jez P, 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 MCM, Martins TD, Hensel C, Herrera CM, Moraes A, Pol ME, Teles PR, Chagas EBBD, Carvalho W, Chinellato J, Custodio A, Da Costa EM, Damiao DD, Martins CD, De Souza SF, Guativa LMH, Malbouisson H, Figueiredo DM, Mundim L, Nogima H, Da Silva WLP, Santaolalla J, Santoro A, Sznajder A, Manganote EJT, Pereira AV, Ahuja S, Bernardes CA, Dogra S, Tomei TRFP, Gregores EM, 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T, Lassila-Perini K, Lehti S, Linden T, Luukka P, 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 P, de Monchenault GH, Jarry P, Locci E, Malcles J, Rander J, Rosowsky A, Titov M, Zghiche A, Baffioni S, Beaudette F, Busson P, Cadamuro L, Chapon E, Charlot C, Dahms T, Davignon O, Filipovic N, Florent A, de Cassagnac RG, Mastrolorenzo L, Mine P, Naranjo IN, Nguyen M, Ochando C, Ortona G, Paganini P, 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, Chanon N, Collard C, Conte E, Fontaine JC, Gele D, Goerlach U, Goetzmann C, Le Bihan AC, Merlin JA, Skovpen K, Van Hove P, Gadrat S, Beauceron S, Beaupere N, Bernet C, Boudoul G, Bouvier E, Brochet S, Montoya CAC, Chasserat J, Chierici R, Contardo D, Courbon B, Depasse P, 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 P, Viret S, Xiao H, Lomidze D, Autermann C, Beranek S, Bontenackels M, 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, 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, Pook T, Radziej M, Reithler H, Rieger M, Schmitz SA, Sonnenschein L, Teyssier D, Thuer S, Cherepanov V, Erdogan Y, Flugge G, Geenen H, Geisler M, Ahmad WH, Hoehle F, Kargoll B, Kress T, Kuessel Y, Kunsken A, Lingemann J, 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, Garcia JG, Geiser A, Gizhko A, Gunnellini P, Hauk J, Hempel M, Jung H, Kalogeropoulos A, Karacheban O, Kasemann M, Katsas P, Kieseler J, Kleinwort C, Korol I, Lange W, Leonard J, Lipka K, Lobanov A, Mankel R, Marfin I, Melzer-Pellmann IA, Meyer AB, Mittag G, Mnich J, Mussgiller A, Naumann-Emme S, Nayak A, Ntomari E, Perrey H, Pitzl D, Placakyte R, Raspereza A, Cipriano PMR, Roland B, Sahin MO, Salfeld-Nebgen J, Saxena P, Schoerner-Sadenius T, Schroder M, Seitz C, Spannagel S, Wissing C, Blobel V, Vignali MC, Draeger AR, Ere J, Garutti E, Goebel K, Gonzalez D, Gorner M, Haller J, Hoffmann M, Hoing RS, Junkes A, Kirschenmann H, Klanner R, Kogler R, Lapsien T, Lenz T, Marchesini I, Marconi D, Meyer M, Nowatschin D, Ott J, Peiffer T, Perieanu A, Pietsch N, Poehlsen J, Rathjens D, Sander C, Schettler H, Schleper P, Schlieckau E, Schmidt A, Seidel M, Sola V, Stadie H, Steinbruck G, Tholen H, Troendle D, Usai E, Vanelderen L, Vanhoefer A, Akbiyik M, Barth C, Baus C, Berger J, Boser 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, Katkov I, Kornmayer A, Pardo PL, 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, Markou A, Psallidas A, Topsis-Giotis I, Agapitos A, Kesisoglou S, Panagiotou A, Saoulidou N, Tziaferi E, Evangelou I, Flouris G, Foudas C, Kokkas P, Loukas N, Manthos N, Papadopoulos I, Paradas E, Strologas J, Bencze G, Hajdu C, Hazi A, Hidas P, Horvath D, Sikler F, Veszpremi V, Vesztergombi G, Zsigmond AJ, Beni N, Czellar S, Karancsi J, Molnar J, Palinkas J, Szillasi Z, Bartok M, Makovec A, Raics P, Trocsanyi ZL, Mal P, 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, Kumar A, Kumar A, Bhardwaj A, Choudhary BC, Kumar A, Malhotra S, Naimuddin M, Ranjan K, Sharma R, Sharma V, Banerjee S, Bhattacharya S, Chatterjee K, Dey S, Dutta S, Gomber B, 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, Dutta D, Jha V, Kumar V, Mohanty AK, Pant LM, Shukla P, Topkar A, Aziz T, Banerjee S, Bhowmik S, Chatterjee RM, Dewanjee RK, Dugad S, Ganguly S, Ghosh S, Guchait M, Gurtu A, Kole G, Kumar S, Maity M, Majumder G, Mazumdar K, Mohanty GB, Parida B, 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, Sharma A, Silvestris L, Venditti R, Verwilligen P, Abbiendi G, Battilana C, Benvenuti C, 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, 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, Gallo E, Gonzi S, Gori V, Lenzi P, 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, Robutti E, Tosi S, Dinardo ME, Fiorendi S, Gennai S, Gerosa R, Ghezzi A, Govoni P, Lucchini MT, 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 P, Sciacca C, Azzi P, Bacchetta N, Bisello D, Branca A, Carlin R, De Oliveira ACA, Checchia P, Dall'Osso M, Dorigo T, Gasparini F, Gasparini U, Gozzelino A, Lacaprara S, Margoni M, Meneguzzo AT, Montecassiano F, Passaseo M, Pazzini J, Pozzobon N, Ronchese P, Simonetto F, Torassa E, Tosi M, Zanetti M, Zotto P, Zucchetta A, Zumerle G, Gabusi M, Magnani A, Ratti SP, Re V, Riccardi C, Salvini P, Vai I, Vitulo P, Solestizi LA, Biasini M, Bilei GM, Ciangottini D, Fano L, Lariccia P, Mantovani G, Menichelli M, 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, Fedi G, 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 T, 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 P, Micheli F, Organtini G, Paramatti R, Preiato F, 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, Covarelli R, De Remigis P, Degano A, Demaria N, Finco L, Kiani B, Mariotti C, Maselli S, Migliore E, Monaco V, Musich M, Obertino MM, Pacher L, Pastrone N, Pelliccioni M, Angioni GLP, Romero A, Ruspa M, Sacchi R, Solano A, Staiano A, 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, Park H, Sakharov A, Son DC, 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 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, Ibrahim ZA, Komaragiri JR, Ali MABM, Idris FM, Abdullah WATW, Linares EC, Castilla-Valdez H, De la Cruz-Burelo E, Heredia-de La Cruz I, Hernandez-Almada A, Lopez-Fernandez R, Sanchez GR, 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 P, Brona G, Bunkowski K, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Olszewski M, Walczak M, Bargassa P, Silva CBDE, Di Francesco A, Faccioli P, Parracho PGF, Gallinaro M, Iglesias LL, Nguyen F, Antunes JR, Seixas J, Toldaiev O, Vadruccio D, Varela J, Vischia P, Afanasiev S, Bunin P, Gavrilenko M, Golutvin I, Gorbunov I, Kamenev A, Karjavin V, Konoplyanikov V, Lanev A, Malakhov A, Matveev V, Moisenz P, Palichik V, Perelygin V, Shmatov S, Shulha S, Skatchkov N, Smirnov V, Toriashvili T, Zarubin A, Golovtsov V, Ivanov Y, Kim V, Kuznetsova E, Levchenko P, 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, 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, Krychkine V, Petrov V, Ryutin R, Sobol A, Tourtchanovitch L, Troshin S, Tyurin N, 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Dabrowski A, Daponte V, David A, De Gruttola M, De Guio F, De Roeck A, De Visscher S, Di Marco E, Dobson M, Dordevic M, Dupont-Sagorin N, Elliott-Peisert A, Franzoni G, Funk W, Gigi D, Gill K, Giordano D, Girone M, Glege F, Guida R, Gundacker S, Guthoff M, Hammer J, Hansen M, Harris P, Hegeman J, Innocente V, Janot P, Kortelainen MJ, Kousouris K, Krajczar K, Lecoq P, Lourenco C, Magini N, Malgeri L, Mannelli M, Marrouche J, Martelli A, Masetti L, Meijers F, Mersi S, Meschi E, Moortgat F, Morovic S, Mulders M, Nemallapudi MV, Neugebauer H, Orfanelli S, Orsini L, Pape L, Perez E, Petrilli A, Petrucciani G, Pfeiffer A, Piparo D, Racz A, Rolandi G, Rovere M, Ruan M, Sakulin H, Schafer C, Schwick C, Sharma A, Silva P, Simon M, Sphicas P, Spiga D, Steggemann J, Stieger B, Stoye M, Takahashi Y, Treille D, Tsirou A, Veres GI, Wardle N, Wohri HK, Zagozdzinska A, Zeuner WD, Bertl W, Deiters K, Erdmann W, Horisberger R, Ingram Q, Kaestli HC, Kotlinski D, Langenegger U, Rohe T, Bachmair F, Bani L, 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Cumalat JP, Ford WT, Gaz A, Jensen F, Johnson A, Krohn M, Mulholland T, Nauenberg U, Smith JG, Stenson K, Wagner SR, Alexander J, Chatterjee A, Chaves J, Chu J, Dittmer S, Eggert N, Mirman N, Kaufman GN, Patterson JR, Ryd A, Skinnari L, Sun W, Tan SM, Teo WD, Thom J, Thompson J, Tucker J, Weng Y, Wittich P, Abdullin S, Albrow M, Anderson J, Apollinari G, Bauerdick LAT, Beretvas A, Berryhill J, Bhat PC, Bolla G, Burkett K, Butler JN, Cheung HWK, Chlebana F, Cihangir S, Elvira VD, Fisk I, Freeman J, Gottschalk E, Gray L, Green D, Grunendahl S, Gutsche O, Hanlon J, Hare D, Harris RM, Hirschauer J, Hooberman B, Hu Z, Jindariani S, Johnson M, Joshi U, Jung AW, Klima B, Kreis B, Kwan S, Lammel S, Linacre J, Lincoln D, Lipton R, Liu T, De Sa RL, Lykken J, Maeshima K, No JMMF, Outschoorn VIM, Maruyama S, Mason D, McBride P, Merkel P, Mishra K, Mrenna S, Nahn S, Newman-Holmes C, O'Dell V, Prokofyev O, Sexton-Kennedy E, Soha A, Spalding WJ, Spiegel L, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vernieri C, Verzocchi M, Vidal R, Whitbeck A, Yang F, Yin H, Acosta D, Avery P, Bortignon P, Bourilkov D, Carnes A, Carver M, Curry D, Das S, Di Giovanni GP, Field RD, Fisher M, Furic IK, Hugon J, Konigsberg J, Korytov A, Kypreos T, Low JF, Ma P, Matchev K, Mei H, Milenovic P, Mitselmakher G, Muniz L, Rank D, Rinkevicius A, Shchutska L, Snowball M, Sperka D, Wang SJ, Yelton J, Hewamanage S, Linn S, Markowitz P, Martinez G, Rodriguez JL, Ackert A, Adams JR, Adams T, Askew A, Bochenek J, Diamond B, Haas J, Hagopian S, Hagopian V, Johnson KF, Khatiwada A, Prosper H, Veeraraghavan V, Weinberg M, Bhopatkar V, Hohlmann M, Kalakhety H, Mareskas-Palcek D, Roy T, Yumiceva F, Adams MR, Apanasevich L, Berry D, Betts RR, Bucinskaite I, Cavanaugh R, Evdokimov O, Gauthier L, Gerber CE, Hofman DJ, Kurt P, O'Brien C, Gonzalez IDS, Silkworth C, Turner P, Varelas N, Wu Z, Zakaria M, Bilki B, Clarida W, Dilsiz K, Gandrajula RP, Haytmyradov M, Khristenko V, Merlo JP, Mermerkaya H, Mestvirishvili A, Moeller A, Nachtman J, Ogul H, Onel Y, Ozok F, Penzo A, Sen S, Snyder C, Tan P, Tiras E, Wetzel J, Yi K, Anderson I, Barnett BA, Blumenfeld B, Fehling D, Feng L, Gritsan AV, Maksimovic P, Martin C, Nash K, Osherson M, Swartz M, Xiao M, Xin Y, Baringer P, Bean A, Benelli G, Bruner C, Gray J, Kenny RP, Majumder D, Malek M, Murray M, Noonan D, Sanders S, Stringer R, Wang Q, Wood JS, Chakaberia I, Ivanov A, Kaadze K, Khalil S, Makouski M, Maravin Y, Saini LK, Skhirtladze N, Svintradze I, Lange D, Rebassoo F, Wright D, Anelli C, Baden A, Baron O, Belloni A, Calvert B, Eno SC, Gomez JA, Hadley NJ, Jabeen S, Kellogg RG, Kolberg T, Lu Y, Mignerey AC, Pedro K, Shin YH, Skuja A, Tonjes MB, Tonwar SC, Apyan A, Barbieri R, Baty A, Bierwagen K, Brandt S, Busza W, Cali IA, Di Matteo L, Ceballos GG, Goncharov M, Gulhan D, Klute M, Lai YS, Lee YJ, Levin A, Luckey PD, Mcginn C, Niu X, Paus C, Ralph D, Roland C, Roland G, Stephans GSF, Sumorok K, Varma M, Velicanu D, Veverka J, Wang J, Wang TW, Wyslouch B, Yang M, Zhukova V, Dahmes B, Finkel A, Gude A, Kao SC, Klapoetke K, Kubota Y, Mans J, Nourbakhsh S, Rusack R, Tambe N, Turkewitz J, Acosta JG, Oliveros S, Avdeeva E, Bloom K, Bose S, Claes DR, Dominguez A, Fangmeier C, Suarez RG, Kamalieddin R, Keller J, Knowlton D, Kravchenko I, Lazo-Flores J, Meier F, Monroy J, Ratnikov F, Siado JE, Snow GR, Alyari M, Dolen J, George J, Godshalk A, Iashvili I, Kaisen J, Kharchilava A, Kumar A, Rappoccio S, Alverson G, Barberis E, Baumgartel D, Chasco M, Hortiangtham A, Massironi A, Morse DM, Nash D, Orimoto T, De Lima RT, Trocino D, Wang RJ, Wood D, Zhang J, Hahn KA, Kubik A, Mucia N, Odell N, Pollack B, Pozdnyakov A, Schmitt M, Stoynev S, Sung K, Trovato M, Velasco M, Won S, Brinkerhoff A, Dev N, Hildreth M, Jessop C, Karmgard DJ, Kellams N, Lannon K, Lynch S, Marinelli N, Meng F, Mueller C, Musienko Y, Pearson T, Planer M, Ruchti R, Smith G, Valls N, Wayne M, Wolf M, Woodard A, Antonelli L, Brinson J, Bylsma B, Durkin LS, 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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 P, Walker M, Foerster M, 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, Suarez I, Tatarinov A, Ulmer KA, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero PR, Faulkner J, Kovitanggoon K, 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 P, 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 P, Sturdy J, Belknap DA, Carlsmith D, Cepeda M, Christian A, Dasu S, Dodd L, Duric S, Friis E, Hall-Wilton R, Herndon M, Herve A, Klabbers P, 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, Smith N, Smith WH, Taylor D, Woods N
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Search for third-generation scalar leptoquarks in the t tau channel in proton-proton collisions at root s = 8 TeV (vol 7, 042, 2015)
JOURNAL OF HIGH ENERGY PHYSICS 2016 NOV 9; ?(11):? Article 056
Altieri MS, Almasry I, Jones T, McPhee C, McCormack JE, Huang EC, Eckardt P, Shapiro MJ, Eckardt S, Vosswinkel JA, Jawa RS
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Implantable cardioverter defibrillators and permanent pacemakers: prevalence and patient outcomes after trauma
AMERICAN JOURNAL OF SURGERY 2016 NOV; 212(5):953-960
BACKGROUND: The prevalence and outcomes of older trauma patients with implantable cardioverter defibrillators (ICDs) or permanent pacemakers (PPMs) is unknown. METHODS: The trauma registry at a regional trauma center was reviewed for blunt trauma patients, aged >= 60 years, admitted between 2007 and 2014. Medical records of cardiac devices patients were reviewed. RESULTS: Of 4,193 admissions, there were 146 ICD, 233 PPM, and 3,814 no device patients; median Injury Severity Score was 9. Most cardiac device patients had substantial underlying heart disease. Patients with ICDs (13.0%) and PPMs (8.6%) had higher mortality rates than no device patients (5.6%, P = .0002). Among cardiac device patients who died, the device was functioning properly in all that were interrogated; the most common cause of death was intracranial hemorrhage. On propensity score analysis, cardiac devices were not independent predictors of mortality but rather surrogate variables associated with other predictors of mortality. CONCLUSIONS: Approximately 9.0% of admitted older patients had cardiac devices. Their presence identified patients who had higher mortality rates, likely because of their underlying comorbidities, including cardiac dysfunction. Published by Elsevier Inc.
McGinn J, Marraffini LA
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CRISPR-Cas Systems Optimize Their Immune Response by Specifying the Site of Spacer Integration
MOLECULAR CELL 2016 NOV 3; 64(3):616-623
CRISPR-Cas systems defend prokaryotes against viruses and plasmids. Short DNA segments of the invader, known as spacers, are stored in the CRISPR array as immunological memories. New spacers are added invariably to the 50 end of the array; therefore, the first spacer matches the latest foreign threat. Whether this highly polarized order of spacer insertion influences CRISPR-Cas immunity has not been explored. Here we show that a conserved sequence located immediately upstream of the CRISPR array specifies the site of new spacer integration. Mutation of this sequence results in erroneous incorporation of new spacers into the middle of the array. We show that spacers added through polarized acquisition give rise to more robust CRISPR-Cas immunity than spacers added to the middle of the array. This study demonstrates that the CRISPR-Cas system specifies the site of spacer integration to optimize the immune response against the most immediate threat to the host.
Hatzi K, Catera R, Atanasio CM, Fischetti VA, Allen SL, Kolitz JE, Rai KR, Chu CC, Chiorazzi N
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Chronic lymphocytic leukemia immunoglobulins display bacterial reactivity that converges and diverges from auto-/poly-reactivity and IGHV mutation status
CLINICAL IMMUNOLOGY 2016 NOV; 172(?):44-51
Chronic lymphocytic leukemia (CLL) is an incurable leukemia of unknown etiology. Multiple studies suggest that the structure of the variable domains of the surface IGs on these cells, and signaling through them, play key roles in developing the disease. Hence, CLL appears to be driven by antigen-BCR interactions, and identifying the selecting antigens involved in this process is an important goal. We studied the antigen-binding characteristics of 23 CLL-derived, recombinantly-expressed IGs with 5 pathogenic bacteria, determining that CLL IGs differ in bacterial reactivity based on IGHV gene use, mutation status, and association with IGHD and IGHJ genes ("stereotypy"). Although most bacterial-reactive IGs followed the paradigm that IGHV-unmutated IGs were more auto-/poly-reactive, several did not. In addition, some CLL IGs were bacterial mono-reactive, and these displayed IGKV use biases. These findings are consistent with CLL B cells being driven into the leukemogenic process by bacterial as well as auto- antigens. (C) 2016 Published by Elsevier Inc.
Etoc F, Metzger J, Ruzo A, Kirst C, Yoney A, Ozair MZ, Brivanlou AH, Siggia ED
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A Balance between Secreted Inhibitors and Edge Sensing Controls Gastruloid Self-Organization
DEVELOPMENTAL CELL 2016 NOV 7; 39(3):302-315
The earliest aspects of human embryogenesis remain mysterious. To model patterning events in the human embryo, we used colonies of human embryonic stem cells (hESCs) grown on micropatterned substrate and differentiated with BMP4. These gastruloids recapitulate the embryonic arrangement of the mammalian germ layers and provide an assay to assess the structural and signaling mechanisms patterning the human gastrula. Structurally, high density hESCs localize their receptors to transforming growth factor 13 at their lateral side in the center of the colony while maintaining apical localization of receptors at the edge. This relocalization insulates cells at the center from apically applied ligands while maintaining response to basally presented ones. In addition, BMP4 directly induces the expression of its own inhibitor, NOGGIN, generating a reaction-diffusion mechanism that underlies patterning. We develop a quantitative model that integrates edge sensing and inhibitors to predict human fate positioning in gastruloids and, potentially, the human embryo.
Bahng S, Hayama R, Marians KJ
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MukB-mediated Catenation of DNA Is ATP and MukEF Independent
JOURNAL OF BIOLOGICAL CHEMISTRY 2016 NOV 11; 291(46):23999-24008
Properly condensed chromosomes are necessary for accurate segregation of the sisters after DNA replication. The Escherichia coli condesin is MukB, a structural maintenance of chromosomes (SMC)-like protein, which forms a complex with MukE and the kleisin MukF. MukB is known to be able to mediate knotting of a DNA ring, an intramolecular reaction. In our investigations of how MukB condenses DNA we discovered that it can also mediate catenation of two DNA rings, an intermolecular reaction. This activity of MukB requires DNA binding by the head domains of the protein but does not require either ATP or its partner proteins MukE or MukF. The ability of MukB to mediate DNA catenation underscores its potential for bringing distal regions of a chromosome together.
Masaki H, Kato-Itoh M, Takahashi Y, Umino A, Sato H, Ito K, Yanagida A, Nishimura T, Yamaguchi T, Hirabayashi M, Era T, Loh KM, Wu SM, Weissman IL, Nakauchi H
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Inhibition of Apoptosis Overcomes Stage-Related Compatibility Barriers to Chimera Formation in Mouse Embryos
Cell Stem Cell 2016 NOV 3; 19(5):587-592
Cell types more advanced in development than embryonic stem cells, such as EpiSCs, fail to contribute to chimeras when injected into pre-implantation-stage blastocysts, apparently because the injected cells undergo apoptosis. Here we show that transient promotion of cell survival through expression of the anti-apoptotic gene BCL2 enables EpiSCs and Sox17(+) endoderm progenitors to integrate into blastocysts and contribute to chimeric embryos. Upon injection into blastocyst, BCL2-expressing EpiSCs contributed to all bodily tissues in chimeric animals while Sox17(+) endoderm progenitors specifically contributed in a region-specific fashion to endodermal tissues. In addition, BCL2 expression enabled rat EpiSCs to contribute to mouse embryonic chimeras, thereby forming interspecies chimeras that could survive to adulthood. Our system therefore provides a method to overcome cellular compatibility issues that typically restrict chimera formation. Application of this type of approach could broaden the use of embryonic chimeras, including region-specific chimeras, for basic developmental biology research and regenerative medicine.
Randesi M, van den Brink W, Levran O, Blanken P, Butelman ER, Yuferov V, da Rosa JC, Ott J, van Ree JM, Kreek MJ
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Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence
DRUG AND ALCOHOL DEPENDENCE 2016 NOV 1; 168(?):164-169
Background: Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence. Methods: Genetic information from four subject groups was collected: non-dependent opioid users (NOD) [n = 163]; opioid-dependent (OD) patients in methadone maintenance treatment (MMT) [n = 143]; opioid-dependent MMT-resistant patients in heroin-assisted treatment (HAT) [n=138]; and healthy controls with no history of opioid use (HC) [n = 153]. Eighty-two variants in eight opioid system genes were studied. To establish the role of these genes in (a) non-dependent opioid use, and (b) heroin dependence, the following groups were compared: HC vs. NOD; HC vs. OD (MMT+HAT); and NOD vs. OD (MMT+HAT). Results: Five unique SNPs in four genes showed nominally significant associations with non-dependent opioid use and heroin dependence. The association of the delta opioid receptor (OPRD1) intronic SNP rs2236861 with non-dependent opioid use (HC vs. NOD) remained significant after correction for multiple testing (OR= 0.032; p(corrected) = 0.015). This SNP exhibited a significant gene-gene interaction with prepronociceptin (PNOC) SNP rs2722897 (OR = 5.24; p(corrected) = 0.041) (HC vs. NOD). Conclusions: This study identifies several new and some previously reported associations of variants with heroin dependence and with non-dependent opioid use, an important and difficult to obtain group not extensively studied previously. Further studies are warranted to confirm and elucidate the potential roles of these variants in the vulnerability to illicit drug use and drug addiction. (C) 2016 Elsevier Ireland Ltd. All rights reserved.