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Alabi RO, Glomski K, Haxaire C, Weskamp G, Monette S, Blobel CP
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ADAM10-Dependent Signaling Through Notchl and Notch4 Controls Development of Organ-Specific Vascular Beds
CIRCULATION RESEARCH 2016 AUG 5; 119(4):519-+
Rationale: Endothelial Notch signaling is critical for early vascular development and survival. Yet, previously described mice lacking endothelial a disintegrin and metalloproteinase 10 (ADAM10), a key regulator of Notch signaling, survived into adulthood with organ-specific vascular defects. These findings raised questions about whether these vascular defects were related to Notch signaling or other functions of ADAM10. Objective: The aims of the study are to determine whether compensatory or redundant functions of ADAM17 in Notch signaling can explain the survival of Adam10 Delta EC mice, explore the contribution of different Tie2-Cre transgenes to the differences in survival, and establish whether the Adam10 Delta EC vascular phenotypes can he recapitulated by inactivation of Notch receptors in endothelial cells. Methods and Results: Mice lacking ADAM10 and ADAM17 in endothelial cells (Adam10/Adam17 Delta EC), which survived postnatally with organ-specific vascular defects, resembled Adam10 Delta EC mice. In contrast, Adam10 Delta EC mice generated with the Tie2Cre transgene previously used to inactivate endothelial Notch (Adam10 Delta ECFlv) died by E10.5. Quantitative polymerase chain reaction analysis demonstrated that Cre-mediated recombination occurs earlier in Adam10 Delta ECFlv mice than in the previously described Adam10 Delta EC mice. Finally, mice lacking endothelial Notchl (Notch1 Delta EC) share some organ-specific vascular defects with Adam10 Delta EC mice, whereas Notch4(-/-) mice lacking endothelial Notchl (Notch1 Delta EC/Notch4(-/-)) had defects in all vascular beds affected in Adam10 Delta EC mice. Conclusions: Our results argue against a major role for ADAM17 in endothelial Notch signaling and clarify the difference in phenotypes of previously described mice lacking ADAM10 or Notch in endothelial cells. Most notably, these findings uncover new roles for Notch signaling in the development of organ-specific vascular beds.
Aaltonen T, Amerio S, Amidei D, Anastassov A, Annovi A, Antos J, Apollinari G, Appel JA, Arisawa T, Artikov A, Asaadi J, Ashmanskas W, Auerbach B, Aurisano A, Azfar F, Badgett W, Bae T, Barbaro-Galtieri A, Barnes VE, Barnett BA, Barria P, Bartos P, Bauce M, Bedeschi F, Behari S, Bellettini G, Bellinger J, Benjamin D, Beretvas A, Bhatti A, Bland KR, Blumenfeld B, Bocci A, Bodek A, Bortoletto D, Boudreau J, Boveia A, Brigliadori L, Bromberg C, Brucken E, Budagov J, Budd HS, Burkett K, Busetto G, Bussey P, Butti P, Buzatu A, Calamba A, Camarda S, Campanelli M, Canelli F, Carls B, Carlsmith D, Carosi R, Carrillo S, Casal B, Casarsa M, Castro A, Catastini P, Cauz D, Cavaliere V, Cavalli-Sforza M, Cerri A, Cerrito L, Chen YC, Chertok M, Chiarelli G, Chlachidze G, Cho K, Chokheli D, Clark A, Clarke C, Convery ME, Conway J, Corbo M, Cordelli M, Cox CA, Cox DJ, Cremonesi M, Cruz D, Cuevas J, Culbertson R, d'Ascenzo N, Datta M, De Barbaro P, Demortier L, Deninno M, Devoto F, d'Errico M, Di Canto A, Di Ruzza B, Dittmann JR, D'Onofrio M, Donati S, Dorigo M, Driutti A, Ebina K, Edgar R, Elagin A, Erbacher R, Errede S, Esham B, Eusebi R, Farrington S, Ramos JPF, Field R, Flanagan G, Forrest R, Franklin M, Freeman JC, Frisch H, Funakoshi Y, Garfinkel AF, Garosi P, Gerberich H, Gerchtein E, Giagu S, Giakoumopoulou V, Gibson K, Ginsburg CM, Giokaris N, Giromini P, Giurgiu G, Glagolev V, Glenzinski D, Gold M, Goldin D, Golossanov A, Gomez G, Gomez-Ceballos G, Goncharov M, Lopez OG, Gorelov I, Goshaw AT, Goulianos K, Gramellini E, Grinstein S, Grosso-Pilcher C, Group RC, da Costa JG, Hahn SR, Han JY, Happacher F, Hara K, Hare M, Harr RF, Harrington-Taber T, Hatakeyama K, Hays C, Heinrich J, Herndon M, Hocker A, Hong Z, Hopkins W, Hou S, Hughes RE, Husemann U, Huston J, Introzzi G, Iori M, Ivanov A, James E, Jang D, Jayatilaka B, Jeon EJ, Jindariani S, Jones M, Joo KK, Jun SY, Junk TR, Kambeitz M, Kamon T, Karchin PE, Kasmi A, Kato Y, Ketchum W, Keung J, Kilminster B, Kim DH, Kim HS, Kim JE, Kim MJ, Kim SB, Kim SH, Kim YK, Kim YJ, Kimura N, Kirby M, Knoepfel K, Kondo K, Kong DJ, Konigsberg J, Kotwal AV, Kreps M, Kroll J, Kruse M, Kuhr T, Kurata M, Laasanen AT, Lammel S, Lancaster M, Lannon K, Latino G, Lee HS, Lee JS, Leone S, Lewis JD, Limosani A, Lipeles E, Liu H, Liu Q, Liu T, Lockwitz S, Loginov A, Lucchesi D, Lueck J, Lujan P, Lukens P, Lungu G, Lys J, Lysak R, Madrak R, Maestro P, Malik S, Manca G, Manousakis-Katsikakis A, Margaroli F, Marino P, Martinez M, Matera K, Mattson ME, Mazzacane A, Mazzanti P, McNulty R, Mehta A, Mehtala P, Mesropian C, Miao T, Mietlicki D, Mitra A, Miyake H, Moed S, Moggi N, Moon CS, Moore R, Morello MJ, Mukherjee A, Muller T, Murat P, Mussini M, Nachtman J, Nagai Y, Naganoma J, Nakano I, Napier A, Nett J, Neu C, Nigmanov T, Nodulman L, Noh SY, Norniella O, Oakes L, Oh SH, Oh YD, Oksuzian I, Okusawa T, Orava R, Ortolan L, Pagliarone C, Palencia E, Palni P, Papadimitriou V, Parker W, Pauletta G, Paulini M, Paus C, Phillips TJ, Piacentino G, Pianori E, Pilot J, Pitts K, Plager C, Pondrom L, Poprocki S, Potamianos K, Prokoshin F, Pranko A, Ptohos F, Punzi G, Ranjan N, Fernandez IR, Renton P, Rescigno M, Riddick T, Rimondi F, Ristori L, Robson A, Rodriguez T, Rolli S, Ronzani M, Roser R, Rosner JL, Ruffini F, Ruiz A, Russ J, Rusu V, Safonov A, Sakumoto WK, Sakurai Y, Santi L, Sato K, Saveliev V, Savoy-Navarro A, Schlabach P, Schmidt EE, Schwarz T, Scodellaro L, Seidel S, Seiya Y, Semenov A, Sforza F, Shalhout SZ, Shears T, Shepard PF, Shimojima M, Shochet M, Shreyber-Tecker I, Simonenko A, Sinervo P, Sliwa K, Smith JR, Snider FD, Sorin V, Song H, Stancari M, Denis RS, Stelzer B, Stelzer-Chilton O, Stentz D, Strologas J, Sudo Y, Sukhanov A, Suslov I, Takemasa K, Takeuchi Y, Tang J, Tecchio M, Teng PK, Thom J, Thomson E, Thukral V, Toback D, Tokar S, Tollefson K, Tomura T, Tonelli D, Torre S, Torretta D, Totaro P, Trovato M, Ukegawa F, Uozumi S, Vazquez F, Velev G, Vellidis C, Vernieri C, Vidal M, Vilar R, Vizan J, Vogel M, Volpi G, Wagner P, Wallny R, Wang SM, Warburton A, Waters D, Wester WC, Whiteson D, Wicklund AB, Wilbur S, Williams HH, Wilson JS, Wilson P, Winer BL, Wittich P, Wolbers S, Wolfe H, Wright T, Wu X, Wu Z, Yamamoto K, Yamato D, Yang T, Yang UK, Yang YC, Yao WM, Yeh GP, Yi K, Yoh J, Yorita K, Yoshida T, Yu GB, Yu I, Zanetti AM, Zeng Y, Zhou C, Zucchelli S
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Measurement of the WW and WZ production cross section using final states with a charged lepton and heavy-flavor jets in the full CDF Run II data set
PHYSICAL REVIEW D 2016 AUG 23; 94(3):? Article 032008
We present a measurement of the total WW and WZ production cross sections in p (p) over bar collision at root s = 1.96 TeV, in a final state consistent with leptonic W boson decay and jets originating from heavy-flavor quarks from either a W or a Z boson decay. This analysis uses the full data set collected with the CDF II detector during Run II of the Tevatron collider, corresponding to an integrated luminosity of 9.4 fb(-1). An analysis of the dijet mass spectrum provides 3.7 sigma evidence of the summed production processes of either WW or WZ bosons with a measured total cross section of sigma(WW+WZ) = 13.7 +/- 3.9 pb. Independent measurements of the WW and WZ production cross sections are allowed by the different heavy- flavor decay patterns of the W and Z bosons and by the analysis of secondary- decay vertices reconstructed within heavy- flavor jets. The productions of WW and of WZ dibosons are independently seen with significances of 2.9s and 2.1s, respectively, with total cross sections of sigma(WW) = 9.4 +/- 4.2 pb and sigma(WZ) = 3.7(-2.2)(+2.5) pb. The measurements are consistent with standard- model predictions.
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Cruz-Burelo E, Heredia-De La Cruz I, Hernandez-Almada A, Lopez-Fernandez R, Guisao JM, Sanchez-Hernandez A, Moreno SC, Valencia FV, Pedraza I, Ibarguen HAS, Pineda AM, Krofcheck D, Butler PH, Ahmad A, Ahmad M, Hassan Q, Hoorani HR, Khan WA, Khurshid T, Shoaib M, Waqas M, Bialkowska H, Bluj M, Boimska B, Frueboes T, Gorski M, Kazana M, Nawrocki K, Romanowska-Rybinska K, Szleper M, Traczyk P, Zalewski P, Brona G, Bunkowski K, Byszuk A, 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, Hollar J, Leonardo N, 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, KarjJavin V, Lanev A, Malakhov A, Matveev V, Moisenz P, Palichik V, Perelygin V, Shmatov S, Shulha S, Skatchkov N, Smirnov V, 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, Chadeeva M, Chistov R, Danilov M, Rusinov V, Tarkovskii E, Andreev V, Azarkin M, Dremin I, Kirakosyan M, Leonidov A, Mesyats G, Rusakov SV, Baskakov A, Belyaev A, Boos E, Ershov A, Gribushin A, Khein L, Klyukhin V, Kodolova O, Lokhtin I, Lukina O, Miagkov 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, Uzunian A, Volkov A, Adzic P, Cirkovic P, Devetak D, Milosevic J, Rekovic V, Maestre JA, Calvo E, Cerrada M, Llatas MC, Colino N, De La Cruz B, Peris AD, Del Valle AE, Bedoya CF, Ramos JPF, Flix J, Fouz MC, Garcia-Abia P, Lopez OG, Lopez SG, Hernandez JM, Josa MI, De Martino EN, Yzquierdo APC, Pelayo JP, Olmeda AQ, Redondo I, Romero L, Soares MS, Albajar C, de Troconiz JF, Missiroli M, Moran D, Cuevas J, Menendez JF, Folgueras S, Caballero IG, Cortezon EP, Garcia JMV, Cabrillo IJ, Calderon A, De Saa JRC, Curras E, Manzano PD, Fernandez M, Garcia-Ferrero J, Gomez G, Virto AL, Marco J, Marco R, Rivero CM, Matorras F, Gomez JP, Rodrigo T, Rodriguez-Marrero AY, Ruiz-Jimeno A, Scodellaro L, Trevisani N, Vila I, Cortabitarte RV, Abbaneo D, Auffray E, Auzinger G, Bachtis M, Baillon P, Ball AH, Barney D, Benaglia A, Bendavid J, Benhabib L, Berruti GM, Bloch P, Bocci A, Bonato A, Botta C, Breuker H, Camporesi T, Castello R, Cepeda M, Cerminara G, D'Alfonso M, d'Enterria D, Dabrowski A, Daponte V, David A, De Gruttola M, De Guio F, De Roeck A, Di Marco E, Dobson M, Dordevic M, Dorney B, du Pree T, Duggan D, Dunser M, Dupont N, Elliott-Peisert A, Franzoni G, Fulcher J, Funk W, Gigi D, Gill K, Giordano D, Girone M, Glege F, Guida R, Gundacker S, Guthoff M, Hammer J, Harris P, Hegeman J, Innocente V, Janot P, Kirschenmann H, Kortelainen MJ, Kousouris K, Lecoq P, Lourenco C, Lucchini MT, Magini N, Malgeri L, Mannelli M, 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, Peruzzi M, Petrilli A, Petrucciani G, Pfeiffer A, Pierini M, Piparo D, Racz A, Reis T, Rolandi G, Rovere M, Ruan M, Sakulin H, Schafer C, Schwick C, Seidel M, Sharma A, Silva P, Simon M, Sphicas P, Steggemann J, Stieger B, Stoye M, Takahashi Y, Treille D, Triossi A, 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, Bianchini L, Casal B, Dissertori G, Dittmar M, Donega M, Eller P, Grab C, Heidegger C, Hits D, Hoss J, Kasieczka G, Lecomte P, Lustermann W, Mangano B, Marionneau M, del Arbol PMR, Masciovecchio M, Meinhard MT, Meister D, Micheli F, Musella P, Nessi-Tedaldi F, Pandolfi F, Pata J, Pauss F, Perrin G, Perrozzi L, Quittnat M, Rossini M, Schonenberger M, Starodumov A, Takahashi M, Tavolaro VR, Theofilatos K, Wallny R, Aarrestad TK, Amsler C, Caminada L, Canelli MF, Chiochia V, De Cosa A, Galloni C, Hinzmann A, Hreus T, Kilminster B, Lange C, Ngadiuba J, Pinna D, Rauco G, Robmann P, Salerno D, Yang Y, Chen KH, Doan TH, Jain S, Khurana R, Konyushikhin M, Kuo CM, Lin W, Lu YJ, Pozdnyakov A, Yu SS, Kumar A, Chang P, Chang YH, Chang YW, Chao Y, Chen KF, Chen PH, Dietz C, Fiori F, Grundler U, Hou WS, Hsiung Y, Liu YF, Lu RS, Moya MM, Petrakou E, Tsai JF, Tzeng YM, Asavapibhop B, Kovitanggoon K, Singh G, Srimanobhas N, Suwonjandee N, Adiguzel A, Damarseckin S, Demiroglu ZS, Dozen C, Dumanoglu I, Girgis S, Gokbulut G, Guler Y, Gurpinar E, Hos I, Kangal EE, Topaksu AK, Onengut G, Ozdemir K, Ozturk S, Cerci DS, Tali B, Topakli H, Zorbilmez C, Bilin B, Bilmis S, Isildak B, Karapinar G, Yalvac M, Zeyrek M, Gulmez E, Kaya M, Kaya O, Yetkin EA, Yetkin T, Cakir A, Cankocak K, Sen S, Vardarli FI, Grynyov B, Levchuk L, Sorokin P, Aggleton R, Ball F, Beck L, Brooke JJ, Burns D, Clement E, Cussans D, Flacher H, Goldstein J, Grimes M, Heath GP, Heath HF, Jacob J, Kreczko L, Lucas C, Meng Z, Newbold DM, Paramesvaran S, Poll A, Sakuma T, El Nasr-Storey SS, Senkin S, Smith D, Smith VJ, Bell KW, Belyaev A, Brew C, Brown RM, Calligaris L, Cieri D, Cockerill DJA, Coughlan JA, Harder K, Harper S, Olaiya E, Petyt D, Shepherd-Themistocleous CH, Thea A, Tomalin IR, Williams T, Worm SD, Baber M, Bainbridge R, Buchmuller O, Bundock A, Burton D, Casasso S, Citron M, Colling D, Corpe L, Dauncey P, Davies G, De Wit A, Della Negra M, Dunne P, Elwood A, Futyan D, Hall G, Iles G, Lane R, Lucas R, Lyons L, Magnan AM, Malik S, Nash J, Nikitenko A, Pela J, Pesaresi M, Raymond DM, Richards A, Rose A, Seez C, Tapper A, Uchida K, Acosta MV, Virdee T, Zenz SC, Cole JE, Hobson PR, Khan A, Kyberd P, Leslie D, Reid ID, Symonds P, Teodorescu L, Turner M, Borzou A, Call K, Dittmann J, Hatakeyama K, Liu H, Pastika N, Charaf O, Cooper SI, Henderson C, Rumerio P, Arcaro D, Avetisyan A, Bose T, Gastler D, Rankin D, Richardson C, Rohlf J, Sulak L, Zou D, Alimena J, Benelli G, Berry E, Cutts D, Ferapontov A, Garabedian A, Hakala J, Heintz U, Jesus O, Laird E, Landsberg G, Mao Z, Narain M, Piperov S, Sagir S, Syarif R, Breedon R, Breto G, Sanchez MCD, Chauhan S, Chertok M, Conway J, Conway R, Cox PT, Erbacher R, Funk G, Gardner M, Ko W, Lander R, Mclean C, Mulhearn M, Pellett D, Pilot J, Ricci-Tam F, Shalhout S, Smith J, Squires M, Stolp D, Tripathi M, Wilbur S, Yohay R, Cousins R, Everaerts P, Florent A, Hauser J, Ignatenko M, Saltzberg D, Takasugi E, Valuev V, Weber M, Burt K, Clare R, Ellison J, Gary JW, Hanson G, Heilman J, Paneva MI, Jandir P, Kennedy E, Lacroix F, Long OR, Malberti M, Negrete MO, Shrinivas A, Wei H, Wimpenny S, Yates BR, Branson JG, Cerati GB, Cittolin S, D'Agnolo RT, Derdzinski M, Holzner A, Kelley R, Klein D, Letts J, Macneill I, Olivito D, Padhi S, Pieri M, Sani M, Sharma V, Simon S, Tadel M, Vartak A, Wasserbaech S, Welke C, Wurthwein F, Yagil A, Della Porta GZ, Bradmiller-Feld J, Campagnari C, Dishaw A, Dutta V, Flowers K, Sevilla MF, Geffert P, George C, Golf F, Gouskos L, Gran J, Incandela J, Mccoll N, Mullin SD, Richman J, Stuart D, Suarez I, West C, Yoo J, Anderson D, Apresyan A, Bornheim A, Bunn J, Chen Y, Duarte J, Mott A, Newman HB, Pena C, Spiropulu M, Vlimant JR, Xie S, Zhu RY, Andrews MB, Azzolini V, Calamba A, Carlson B, Ferguson T, Paulini M, Russ J, Sun M, Vogel H, Vorobiev I, Cumalat JP, Ford WT, Gaz A, Jensen F, Johnson A, Krohn M, Mulholland T, Nauenberg U, Stenson K, Wagner SR, Alexander J, Chatterjee A, Chaves J, Chu J, Dittmer S, Eggert N, Mirman N, Kaufman GN, Patterson JR, Rinkevicius A, Ryd A, Skinnari L, Soffi L, Sun W, Tan SM, Teo WD, Thom J, Thompson J, Tucker J, Weng Y, Wittich P, Abdullin S, Albrow M, Apollinari G, Banerjee S, 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, Hasegawa S, Hirschauer J, Hu Z, Jayatilaka B, Jindariani S, Johnson M, Joshi U, Klima B, Kreis B, Lammel S, Lewis J, Linacre J, Lincoln D, Lipton R, Liu T, De Sa RL, Lykken J, Maeshima K, Marraffino JM, Maruyama S, Mason D, McBride P, Merkel P, Mrenna S, Nahn S, Newman-Holmes C, O'Dell V, Pedro K, Prokofyev O, Rakness G, Sexton-Kennedy E, Soha A, Spalding WJ, Spiegel L, Stoynev S, Strobbe N, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vernieri C, Verzocchi M, Vidal R, Wang M, Weber HA, Whitbeck A, Acosta D, Avery P, Bortignon P, Bourilkov D, Brinkerhoff A, Carnes A, Carver M, Curry D, Das S, Field RD, Furic IK, Konigsberg J, Korytov A, Kotov K, Ma P, Matchev K, Mei H, Milenovic P, Mitselmakher G, Rank D, Rossin R, Shchutska L, Snowball M, Sperka D, Terentyev N, Thomas L, Wang J, Wang S, Yelton J, Linn S, Markowitz P, Martinez G, Rodriguez JL, Ackert A, Adams JR, Adams T, Askew A, Bein S, Bochenek J, Diamond B, Haas J, Hagopian S, Hagopian V, Johnson KF, Khatiwada A, Prosper H, Weinberg M, Baarmand MM, Bhopatkar V, Colafranceschi S, Hohlmann M, Kalakhety H, Noonan 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, Turner P, Varelas N, Wu Z, Zakaria M, Zhang J, Bilki B, Clarida W, Dilsiz K, Durgut S, Gandrajula RP, Haytmyradov M, Khristenko V, Merlo JP, Mermerkaya H, Mestvirishvili A, Moeller A, Nachtman J, Ogul H, Onel Y, Ozok F, Penzo A, Snyder C, Tiras E, Wetzel J, Yi K, Anderson I, Barnett BA, Blumenfeld B, Cocoros A, Eminizer N, Fehling D, Feng L, Gritsan AV, Maksimovic P, Osherson M, Roskes J, Sarica U, Swartz M, Xiao M, Xin Y, You C, Baringer P, Bean A, Bruner C, Kenny RP, Majumder D, Malek M, Mcbrayer W, Murray M, Sanders S, Stringer R, Wang Q, Ivanov A, Kaadze K, Khalil S, Makouski M, Maravin Y, Mohammadi A, Saini LK, Skhirtladze N, Toda S, Lange D, Rebassoo F, Wright D, Anelli C, Baden A, Baron O, Belloni A, Calvert B, Eno SC, Ferraioli C, Gomez JA, Hadley NJ, Jabeen S, Kellogg RG, Kolberg T, Kunkle J, Lu Y, Mignerey AC, Shin YH, Skuja A, Tonjes MB, Tonwar SC, Apyan A, Barbieri R, Baty A, Bi R, Bierwagen K, Brandt S, Busza W, Cali IA, Demiragli Z, Di Matteo L, Ceballos GG, Goncharov M, Gulhan D, Iiyama Y, Innocenti GM, Klute M, Kovalskyi D, Krajczar K, Lai YS, Lee YJ, Levin A, Luckey PD, Marini AC, Mcginn C, Mironov C, Narayanan S, Niu X, Paus C, Roland C, Roland G, Salfeld-Nebgen J, Stephans GSF, Sumorok K, Tatar K, Varma M, Velicanu D, Veverka J, Wang J, Wang TW, Wyslouch B, Yang M, Zhukova V, Benvenuti AC, Dahmes B, Evans A, Finkel A, Gude A, Hansen P, Kalafut S, Kao SC, Klapoetke K, Kubota Y, Lesko Z, Mans J, Nourbakhsh S, Ruckstuhl N, Rusack R, Tambe N, Turkewitz J, Acosta JG, Oliveros S, Avdeeva E, Bartek R, Bloom K, Bose S, Claes DR, Dominguez A, Fangmeier C, Suarez RG, Kamalieddin R, Knowlton D, Kravchenko I, Meier F, Monroy J, Ratnikov F, Siado JE, Snow GR, Alyari M, Dolen J, George J, Godshalk A, Harrington C, Iashvili I, Kaisen J, Kharchilava A, Kumar A, Rappoccio S, Roozbahani B, 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, Bhattacharya S, Hahn KA, Kubik A, Low JF, Mucia N, Odell N, Pollack B, Schmitt M, Sung K, Trovato M, Velasco M, Dev N, Hildreth M, Jessop C, Karmgard DJ, Kellams N, Lannon K, Marinelli N, Meng F, Mueller C, Musienko Y, Planer M, Reinsvold A, Ruchti R, Rupprecht N, Smith G, Taroni S, Valls N, Wayne M, Wolf M, Woodard A, Antonelli L, Brinson J, Bylsma B, Durkin LS, Flowers S, Hart A, Hill C, Hughes R, Ji W, Ling TY, Liu B, Luo W, Puigh D, Rodenburg M, Winer BL, Wulsin HW, Driga O, Elmer P, Hardenbrook J, Hebda P, Koay SA, Lujan P, Marlow D, Medvedeva T, Mooney M, Olsen J, Palmer C, Piroue P, Stickland D, Tully C, Zuranski A, Malik S, Barker A, Barnes VE, Benedetti D, Bortoletto D, Gutay L, Jha MK, Jones M, Jung AW, Jung K, Kumar A, Miller DH, Neumeister N, Radburn-Smith BC, Shi X, Shipsey I, Silvers D, Sun J, Svyatkovskiy A, Wang F, Xie W, Xu L, Parashar N, Stupak J, Adair A, Akgun B, Chen Z, Ecklund KM, Geurts FJM, Guilbaud M, Li W, Michlin B, Northup M, Padley BP, Redjimi R, Roberts J, Rorie J, Tu Z, Zabel J, Betchart B, Bodek A, de Barbaro P, Demina R, Eshaq Y, Ferbel T, Galanti M, Garcia-Bellido A, Han J, Hindrichs O, Khukhunaishvili A, Lo KH, Tan P, Verzetti M, Ciesielski R, Chou JP, Contreras-Campana E, Ferencek D, Gershtein Y, Halkiadakis E, Heindl M, Hidas D, Hughes E, Kaplan S, Elayavalli RK, Lath A, Nash K, Saka H, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Foerster M, Riley G, Rose K, Spanier S, Thapa K, Bouhali O, Hernandez AC, Celik A, Dalchenko M, De Mattia M, Delgado A, Dildick S, Eusebi R, Gilmore J, Huang T, Kamon T, Krutelyov V, Mueller R, Osipenkov I, Pakhotin Y, Patel R, Perloff A, Rathjens D, 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, Ni H, Sheldon P, Tuo S, Velkovska J, Xu Q, Arenton MW, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Neu C, Sinthuprasith T, Sun X, Wang Y, Wolfe E, Wood J, Xia F, Clarke C, Harr R, Karchin PE, Don CKK, Lamichhane P, Sturdy J, Belknap DA, Carlsmith D, Dasu S, Dodd L, Duric S, Gomber B, Grothe M, Herndon M, Herve A, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ruggles T, Sarangi T, Savin A, Sharma A, Smith N, Smith WH, Taylor D, Verwilligen P, Woods N
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Evidence for exclusive gamma gamma -> W (+) W (-) production and constraints on anomalous quartic gauge couplings in pp collisions at and 8 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2016 AUG 22; ?(8):? Article 119
A search for exclusive or quasi-exclusive gamma gamma -> W (+) W (-) production, via pp -> p ((*)) W (+) W (-) p ((*)) -> p ((*)) mu (+/-)e(a") p ((*)) at TeV, is reported using data corresponding to an integrated luminosity of 19.7 fb(-1). Events are selected by requiring the presence of an electron-muon pair with large transverse momentum p (T)(mu (+/-)e(a")) > 30 GeV, and no associated charged particles detected from the same vertex. The 8 TeV results are combined with the previous 7 TeV results (obtained for 5.05 fb(-1) of data). In the signal region, 13 (2) events are observed over an expected background of 3.9 +/- 0.6 (0.84 +/- 0.15) events for 8 (7) TeV, resulting in a combined excess of 3.4 sigma over the background-only hypothesis. The observed yields and kinematic distributions are compatible with the standard model prediction for exclusive and quasi-exclusive gamma gamma -> W (+) W (-) production. Upper limits on the anomalous quartic gauge coupling operators a (0,C) (W) (dimension-6) and f (M0,1,2,3) (dimension-8), the most stringent to date, are derived from the measured dilepton transverse momentum spectrum.
Kung A, Chen YC, Schimpl M, Ni F, Zhu JF, Turner M, Molina H, Overman R, Zhang C
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Development of Specific, Irreversible Inhibitors for a Receptor Tyrosine Kinase EphB3
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2016 AUG 24; 138(33):10554-10560
Erythropoietin-producing human hepatocellular carcinoma (Eph) receptor tyrosine kinases (RTKs) regulate a variety of dynamic cellular events, including cell protrusion, migration, proliferation, and cell fate determination. Small-molecule inhibitors of Eph kinases are valuable tools for dissecting the physiological and pathological roles of Eph. However, there is a lack of small-molecule inhibitors that are selective for individual Eph isoforms due to the high homology within the family. Herein, we report the development of the first potent and specific inhibitors of a single Eph isoform, EphB3. Through structural bioinformatic analysis, we identified a cysteine in the hinge region of the EphB3 kinase domain, a feature that is not shared with any other human kinases. We synthesized and characterized a series of electrophilic quinazolines to target this unique, reactive feature in EphB3. Some of the electrophilic quinazolines selectively and potently inhibited EphB3 both in vitro and in cells. Cocrystal structures of EphB3 in complex with two quinazolines confirmed the covalent linkage between the protein and the inhibitors. A "clickable" version of an optimized inhibitor was created and employed to verify specific target engagement in the whole proteome and to probe the extent and kinetics of target engagement of existing EphB3 inhibitors. Furthermore, we demonstrate that the autophosphorylation of EphB3 within the juxtamembrane region occurs in trans using a specific inhibitor. These exquisitely specific inhibitors will facilitate the dissection of EphB3's role in various biological processes and disease contribution.
Chou HT, Dukovski D, Chambers MG, Reinisch KM, Walz T
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CATCHR, HOPS and CORVET tethering complexes share a similar architecture
NATURE STRUCTURAL & MOLECULAR BIOLOGY 2016 AUG; 23(8):761-763
We show here that the Saccharomyces cerevisiae GARP complex and the Cog1-4 subcomplex of the COG complex, both members of the complexes associated with tethering containing helical rods (CATCHR) family of multisubunit tethering complexes, share the same subunit organization. We also show that HOPS, a tethering complex acting in the endolysosomal pathway, shares a similar architecture, thus suggesting that multisubunit tethering complexes use related structural frameworks.
Marsch LA, Moore SK, Borodovsky JT, Solhkhah R, Badger GJ, Semino S, Jarrett K, Condon KD, Rossettie K, Vincent P, Hajizadeh N, Ducat E
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A randomized controlled trial of buprenorphine taper duration among opioid-dependent adolescents and young adults
ADDICTION 2016 AUG; 111(8):1406-1415
Background and AimsFew randomized controlled trials have evaluated buprenorphine treatment interventions for opioid-dependent youth. Consequently, optimal administration strategies for this cohort are unclear. Our aim was to evaluate the relative efficacy of two different buprenorphine taper lengths in promoting abstinence from illicit opioids and treatment retention among opioid-dependent youth. DesignA double-blind, placebo controlled, multicenter randomized controlled trial. SettingTwo hospital-based research clinics (Manhattan and Brooklyn) in New York City, USA from 2005 to 2010. ParticipantsVolunteer sample of 53 primarily Caucasian participants between the ages of 16 and 24 (n=11 under age 18) who met DSM-IV opioid dependence criteria. InterventionParticipants were assigned randomly to either a 28-day buprenorphine taper (n=28) or 56-day buprenorphine taper (n=25) via a parallel-groups design during a 63-day period. Both groups received behavioral counseling and opioid abstinence incentives. Both taper conditions had a minimum of 1week of placebo dosing at the end of the taper. MeasurementsThe primary outcome was opioid abstinence measured as a percentage of scheduled urine toxicology tests documented to be negative for opioids. The secondary outcome was treatment retention, measured as number of days attended scheduled visits. FindingsIntent-to-treat analyses revealed that participants who received a 56-day buprenorphine taper had a significantly higher percentage of opioid-negative scheduled urine tests compared with participants who received a 28-day buprenorphine taper [35 versus 17%, P=0.039; Cohen's d=0.57, 95% confidence interval (CI)=0.02, 1.13]. Participants who received a 56-day buprenorphine taper were retained in treatment significantly longer than participants who received a 28-day buprenorphine taper (37.5 versus 26.4days, P=0.027; Cohen's d=0.63, 95% CI=0.06, 1.19). Daily attendance requirement was associated with decreased abstinence and shorter retention compared with a two to three times weekly attendance requirement, independent of taper duration. Follow-up data were insufficient to report. ConclusionLonger (56-day) buprenorphine taper produces better opioid abstinence and retention outcomes than shorter (28-day) buprenorphine taper for opioid-dependent youth.
Yu H, Patil KV, Han C, Fabella B, Canlon B, Someya S, Cederroth CR
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GLAST Deficiency in Mice Exacerbates Gap Detection Deficits in a Model of Salicylate-Induced Tinnitus
FRONTIERS IN BEHAVIORAL NEUROSCIENCE 2016 AUG 17; 10(?):? Article 158
Gap detection or gap pre-pulse inhibition of the acoustic startle (GPIAS) has been successfully used in rat and guinea pig models of tinnitus, yet this system has been proven to have low efficacy in CBA mice, with low basal GPIAS and subtle tinnitus-like effects. Here, we tested five mouse strains (CBA, BalbC, CD-1, C57BL/6 and 129sv) for pre-pulse inhibition (PPI) and gap detection with varying interstimulus intervals (ISI) and found that mice from a CBA genetic background had the poorest capacities of suppressing the startle response in the presence of a pre-pulse or a gap. CD-1 mice displayed variable responses throughout all ISI. Interestingly, C57BL/6, 129sv and BalbC showed efficient suppression with either pre-pulses or gaps with shorter ISI. The glutamate aspartate transporter (GLAST) is expressed in support cells from the cochlea and buffers the excess of glutamate. We hypothesized that loss of GLAST function could sensitize the ear to tinnitus-inducing agents, such as salicylate. Using shorter ISI to obtain a greater dynamic range to assess tinnitus-like effects, we found that disruption of gap detection by salicylate was exacerbated across various intensities of a 32-kHz narrow band noise gap carrier in GLAST knockout (KO) mice when compared to their wild-type (WT) littermates. Auditory brainstem responses (ABR) and distortion-product otoacoustic emission (DPOAE) were performed to evaluate the effects on hearing functions. Salicylate caused greater auditory threshold shifts (near 15 dB) in GLAST KO mice than in WT mice across all tested frequencies, despite similarly reduced DPOAE. Despite these changes, inhibition using broad-band gap carriers and 32 kHz pre-pulses were not affected. Our study suggests that GLAST deficiency could become a useful experimental model to decipher the mechanisms underlying drug-induced tinnitus. Future studies addressing the neurological correlates of tinnitus in this model could provide additional insights into the mechanisms of tinnitus.
Alarcon CR, Tavazoie SF
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Endothelial-cell killing promotes metastasis
NATURE 2016 AUG 11; 536(7615):154-155
Van Kempen TA, Narayan A, Waters EM, Marques-Lopes J, Iadecola C, Glass MJ, Pickel VM, Milner TA
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Alterations in the Subcellular Distribution of NADPH Oxidase p47(phox) in Hypothalamic Paraventricular Neurons Following Slow-Pressor Angiotensin II Hypertension in Female Mice With Accelerated Ovarian Failure
JOURNAL OF COMPARATIVE NEUROLOGY 2016 AUG 1; 524(11):2251-2265
At younger ages, women have a lower risk for hypertension than men, but this sexual dimorphism declines with the onset of menopause. These differences are paralleled in rodents following "slow-pressor" angiotensin II (AngII) administration: young male and aged female mice, but not young females, develop hypertension. There is also an established sexual dimorphism both in the cardiovascular response to the neurohypophyseal hormone arginine vasopressin (AVP) and in the expression of oxidative stress. We examined the relationship between AngII-mediated hypertension and the cellular distribution of the superoxide generating NADPH oxidase (NOX) in AVP-expressing hypothalamic paraventricular nucleus (PVN) neurons in "menopausal" female mice. Dual-labeling immunoelectron microscopy was used to determine whether the subcellular distribution of the organizer/adapter NOX p47(phox) subunit is altered in PVN dendrites following AngII administered (14 days) during the "postmenopausal" stage of accelerated ovarian failure (AOF) in young female mice treated with 4-vinylcyclohexene diepoxide. Slow-pressor AngII elevated blood pressure in AOF females and induced a significant increase in near plasmalemmal p47(phox) and a decrease in cytoplasmic p47(phox) in PVN AVP dendrites. These changes are the opposite of those observed in AngII-induced hypertensive male mice (Coleman et al. [2013] J. Neurosci. 33:4308-4316) and may be ascribed in part to baseline differences between young females and males in the near plasmalemmal p47(phox) on AVP dendrites seen in the present study. These findings highlight fundamental differences in the neural substrates of oxidative stress in the PVN associated with AngII hypertension in postmenopausal females compared with males. (C) 2015 Wiley Periodicals, Inc.
Wu YG, Lazzaroni-Tealdi E, Wang Q, Zhang L, Barad DH, Kushnir VA, Darmon SK, Albertini DF, Gleicher N
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Different effectiveness of closed embryo culture system with time-lapse imaging (EmbryoScope (TM)) in comparison to standard manual embryology in good and poor prognosis patients: a prospectively randomized pilot study
REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY 2016 AUG 24; 14(?):? Article 49
Background: Previously manual human embryology in many in vitro fertilization (IVF) centers is rapidly being replaced by closed embryo incubation systems with time-lapse imaging. Whether such systems perform comparably to manual embryology in different IVF patient populations has, however, never before been investigated. We, therefore, prospectively compared embryo quality following closed system culture with time-lapse photography (EmbryoScope (TM)) and standard embryology. We performed a two-part prospectively randomized study in IVF (clinical trial # NCT92256309). Part A involved 31 infertile poor prognosis patients prospectively randomized to EmbryoScope (TM) and standard embryology. Part B involved embryos from 17 egg donor-recipient cycles resulting in large egg/embryo numbers, thus permitting prospectively alternative embryo assignments to EmbryoScope (TM) and standard embryology. We then compared pregnancy rates and embryo quality on day-3 after fertilization and embryologist time utilized per processed embryo. Results: Part A revealed in poor prognosis patients no differences in day-3 embryo scores, implantation and clinical pregnancy rates between EmbryoScope (TM) and standard embryology. The EmbryoScope (TM), however, more than doubled embryology staff time (P < 0.0001). In Part B, embryos grown in the EmbyoScope (TM) demonstrated significantly poorer day-3 quality (depending on embryo parameter between P = 0.005 and P = 0.01). Suspicion that conical culture dishes of the EmbryoScope (TM) (EmbryoSlide (TM)) may be the cause was disproven when standard culture dishes demonstrated no outcome difference in standard incubation. Conclusions: Though due to small patient numbers preliminary, this study raises concerns about the mostly uncontrolled introduction of closed incubation systems with time lapse imaging into routine clinical embryology. Appropriately designed and powered prospectively randomized studies appear urgently needed in well-defined patient populations before the uncontrolled utilization of these instruments further expands.