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Rinaudo P, Albertini D
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Promising noninvasive microscopy imaging technique evaluates metabolic markers in mouse oocytes

FERTILITY AND STERILITY 2018 DEC; 110(7):1271-1271
Boisson-Dupuis S, Ramirez-Alejo N, Li Z, Patin E, Rao G, Kerner G, Lim CK, Krementsov DN, Hernandez N, Ma CS, Zhang Q, Markle J, Martinez-Barricarte R, Payne K, Fisch R, Deswarte C, Halpern J, Bouaziz M, Mulwa J, Sivanesan D, Lazarov T, Naves R, Garcia P, Itan Y, Boisson B, Checchi A, Jabot-Hanin F, Cobat A, Guennoun A, Jackson CC, Pekcan S, Caliskaner Z, Inostroza J, Costa-Carvalho BT, de Albuquerque JAT, Garcia-Ortiz H, Orozco L, Ozcelik T, Abid A, Rhorfi IA, Souhi H, Amrani HN, Zegmout A, Geissmann F, Michnick SW, Muller-Fleckenstein I, Fleckenstein B, Puel A, Ciancanelli MJ, Marr N, Abolhassani H, Balcells ME, Condino-Neto A, Strickler A, Abarca K, Teuscher C, Ochs HD, Reisli I, Sayar EH, El-Baghdadi J, Bustamante J, Hammarstrom L, Tangye SG, Pellegrini S, Quintana-Murci L, Abel L, Casanova JL
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Tuberculosis and impaired IL-23-dependent IFN-gamma immunity in humans homozygous for a common TYK2 missense variant

SCIENCE IMMUNOLOGY 2018 DEC; 3(30):? Article eaau8714
Inherited IL-12R beta 1 and TYK2 deficiencies impair both IL-12- and IL-23 -dependent IFN-gamma immunity and are rare monogenic causes of tuberculosis, each found in less than 1/600,000 individuals. We show that homozygosity for the common TYK2 P1104A allele, which is found in about 1/600 Europeans and between 1/1000 and 1/10,000 individuals in regions other than East Asia, is more frequent in a cohort of patients with tuberculosis from endemic areas than in ethnicity-adjusted controls (P = 8.37 x 10(-8); odds ratio, 89.31; 95% CI, 14.7 to 1725). Moreover, the frequency of P1104A in Europeans has decreased, from about 9% to 4.2%, over the past 4000 years, consistent with purging of this variant by endemic tuberculosis. Surprisingly, we also show that TYK2 P1104A impairs cellular responses to IL-23, but not to IFN-alpha, IL-10, or even IL-12, which, like IL-23, induces IFN-gamma via activation of TYK2 and JAK2. Moreover, TYK2 P1104A is properly docked on cytokine receptors and can be phosphorylated by the proximal JAK, but lacks catalytic activity. Last, we show that the catalytic activity of TYK2 is essential for IL-23, but not IL-12, responses in cells expressing wild-type JAK2. In contrast, the catalytic activity of JAK2 is redundant for both IL-12 and IL-23 responses, because the catalytically inactive P1057A JAK2, which is also docked and phosphorylated, rescues signaling in cells expressing wild-type TYK2. In conclusion, homozygosity for the catalytically inactive P1104A missense variant of TYK2 selectively disrupts the induction of IFN-gamma by IL-23 and is a common monogenic etiology of tuberculosis.
Touhara KK, MacKinnon R
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Molecular basis of signaling specificity between GIRK channels and GPCRs

ELIFE 2018 DEC 10; 7(?):? Article e42908
Stimulated muscarinic acetylcholine receptors (M2Rs) release G beta gamma subunits, which slow heart rate by activating a G protein-gated K+ channel (GIRK). Stimulated beta 2 adrenergic receptors (beta 2ARs) also release G beta gamma subunits, but GIRK is not activated. This study addresses the mechanism underlying this specificity of GIRK activation by M2Rs. K+ currents and bioluminescence resonance energy transfer between labelled G proteins and GIRK show that M2Rs catalyze G beta gamma subunit release at higher rates than beta 2ARs, generating higher G beta gamma concentrations that activate GIRK and regulate other targets of G beta gamma. The higher rate of G beta gamma release is attributable to a faster G protein coupled receptor - G protein trimer association rate in M2R compared to beta 2AR. Thus, a rate difference in a single kinetic step accounts for specificity.
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C, Vanlaer P, Vannerom D, Yonamine R, Zenoni F, Cornelis T, Dobur D, Fagot A, Gul M, Khvastunov I, Poyraz D, Roskas C, Salva S, Trocino D, Tytgat M, Verbeke W, Vit M, Zaganidis N, Bakhshiansohi H, Bondu O, Brochet S, Bruno G, Caputo C, Caudron A, David P, De Visscher S, Delaere C, Delcourt M, Francois B, Giammanco A, Komm M, Krintiras G, Lemaitre V, Magitteri A, Mertens A, Musich M, Piotrzkowski K, Quertenmont L, Saggio A, Marono MV, Wertz S, Zobec J, Alda WL, Alves FL, Alves GA, Brito L, Silva GC, Hensel C, Moraes A, Pol ME, Teles PR, Das Chagas EBB, Carvalho W, Chinellato J, Coelho E, Da Costa EM, Da Silveira GG, Damiao DD, De Souza SF, Guativa LMH, Malbouisson H, De Almeida MM, Herrera CM, Mundim L, Nogima H, Rosas LJS, Santoro A, Sznajder A, Thiel M, Manganote EJT, De Araujo FTD, Pereira AV, Ahuja S, Bernardes CA, Tomei TRFP, Gregores EM, Mercadante PG, Novaes SF, Padula SS, Abad DR, Vargas JCR, Aleksandrov A, Hadjiiska R, Iaydjiev P, Misheva M, Rodozov M, Shopova M, Sultanov G, 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A, Sordini V, Vander Donckt M, Viret S, Zhang S, Toriashvili T, Tsamalaidze Z, Autermann C, Feld L, Kiesel MK, Klein K, Lipinski M, Preuten M, Schomakers C, Schulz J, Teroerde M, Wittmer B, Zhukov V, Albert A, Duchardt D, Endres M, Erdmann M, Erdweg S, Esch T, Fischer R, Guth A, Hebbeker T, Heidemann C, Hoepfner K, Knutzen S, Merschmeyer M, Meyer A, Millet P, Mukherjee S, Pook T, Radziej M, Reithler H, Rieger M, Scheuch F, Teyssier D, Thuer S, Flugge G, Kargoll B, Kress T, Kunsken A, Muller T, Nehrkorn A, Nowack A, Pistone C, Pooth O, Stahl A, Martin MA, Arndt T, Asawatangtrakuldee C, Beernaert K, Behnke O, Behrens U, Martinez AB, Bin Anuar AA, Borras K, Botta V, Campbell A, Connor P, Contreras-Campana C, Costanza F, Pardos CD, Eckerlin G, Eckstein D, Eichhorn T, Eren E, Gallo E, Garcia JG, Geiser A, Luyando JMG, Grohsjean A, Gunnellini P, Guthoff M, Harb A, Hauk J, Hempel M, Jung H, Kasemann M, Keaveney J, Kleinwort C, Korol I, Krucker D, Lange W, Lelek A, Lenz T, Lipka K, Lohmann W, 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Weber M, Weiler T, Williamson S, Wohrmann C, Wolf R, Anagnostou G, Daskalakis G, Geralis T, Kyriakis A, Loukas D, Topsis-Giotis I, Karathanasis G, Kesisoglou S, Panagiotou A, Saoulidou N, Tziaferi E, Kousouris K, Evangelou I, Foudas C, Gianneios P, Katsoulis P, Kokkas P, Mallios S, Manthos N, Papadopoulos I, Paradas E, Strologas J, Triantis FA, Tsitsonis D, Csanad M, Filipovic N, Pasztor G, Suranyi O, Veres GI, Bencze G, Hajdu C, Horvath D, Hunyadi A, Sikler F, Veszpremi V, Vesztergombi G, Beni N, Czellar S, Karancsi J, Makovec A, Molnar J, Szillasi Z, Bartok M, Raics P, Trocsanyi ZL, Ujvari B, Choudhury S, Komaragiri JR, Bahinipati S, Mal P, Mandal K, Nayak A, Sahoo DK, Sahoo N, Swain SK, Bansal S, Beri SB, Bhatnagar V, Chawla R, Dhingra N, Kaur A, Kaur M, Kaur S, Kumar R, Kumari P, Mehta A, Singh JB, Walia G, Bhardwaj A, Chauhan S, Choudhary BC, Garg RB, Keshri S, Kumar A, Kumar A, Malhotra S, Naimuddin M, Ranjan K, Shah A, Sharma R, Bhardwaj R, Bhattacharya R, Bhattacharya S, Bhawandeep U, Bhowmik D, Dey S, Dutt S, Dutta S, Majumdar N, Modak A, Mondal K, Mukhopadhyay S, Nandan S, Purohit A, Rout PK, Roy A, Chowdhury SR, Sarkar S, Sharan M, Singh B, Thakur S, Behera PK, Chudasama R, Dutta D, Jha V, Kumar V, Mohanty AK, Netrakanti PK, Pant LM, Shukla P, Topkar A, Aziz T, Dugad S, Mahakud B, Mitra S, Mohanty GB, Sur N, Sutar B, Banerjee S, Chatterjee S, Das P, Guchait M, Jain S, Kumar S, Maity M, Majumder G, Mazumdar K, Sarkar T, Wickramage N, Dube S, Hegde V, Kapoor A, Kothekar K, Pandey S, Rane A, Sharma S, Chenarani S, Tadavani EE, Etesami SM, Khakzad M, Najafabadi MM, Naseri M, Mehdiabadi SP, Hosseinabadi FR, Safarzadeh B, Zeinali M, Felcini M, Grunewald M, Abbrescia M, Calabria C, Colaleo A, Creanza D, Cristella L, De Filippis N, De Palma M, Errico F, Fiore L, Iaselli G, Lezki S, Maggi G, Maggi M, Marangelli B, Miniello G, My S, Nuzzo S, Pompili A, Pugliese G, Radogna R, Ranieri A, Selvaggi G, Sharma A, Silvestris L, Venditti R, Verwilligen P, Zito G, Abbiendi G, Battilana C, Bonacorsi D, Borgonovi L, Braibant-Giacomelli S, Campanini R, Capiluppi P, Castro A, Cavallo FR, Chhibra SS, Codispoti G, Cuffiani M, Dallavalle GM, Fabbri F, Fanfani A, Fasanella D, Giacomelli P, Grandi C, Guiducci L, Iemmi F, Marcellini S, Masetti G, Montanari A, Navarria FL, Perrotta A, Rossi AM, Rovelli T, Siroli GP, Tosi N, Albergo S, Costa S, Di Mattia A, Giordano F, Potenza R, Tricomi A, Tuve C, Barbagli G, Chatterjee K, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Lenzi P, Meschini M, Paoletti S, Russo L, Sguazzoni G, Strom D, Viliani L, Benussi L, Bianco S, Piccolo D, Primavera F, Calvelli V, Ferro F, Ravera F, Robutti E, Tosi S, Benaglia A, Beschi A, Brianza L, Brivio F, Ciriolo V, Dinardo ME, Fiorendi S, Gennai S, Ghezzi A, Govoni P, Malberti M, Malvezzi S, Manzoni RA, Menasce D, Moroni L, Paganoni M, Pauwels K, Pedrini D, Pigazzini S, Ragazzi S, de Fatis TT, Buontempo S, Cavallo N, Di Guida S, Fabozzi F, Fienga F, Iorio AOM, Khan WA, Lista L, Meola S, Paolucci P, Sciacca C, Thyssen F, Azzi P, Bacchetta N, Benato L, Bisello D, Boletti A, Carlin R, Checchia P, Dall'Osso M, Manzano PD, Dorigo T, Dosselli U, Gasparini F, Gasparini U, Gozzelino A, Lacaprara S, Lujan P, Margoni M, Meneguzzo AT, Pozzobon N, Ronchese P, Rossin R, Simonetto F, Tiko A, Torassa E, Zanetti M, Zotto P, Zumerle G, Braghieri A, Magnani A, Montagna P, Ratti SP, Re V, Ressegotti M, Riccardi C, Salvini P, Vai I, Vitulo P, Solestizi LA, Biasini M, Bilei GM, Cecchi C, Ciangottini D, Fano L, Lariccia P, Leonardi R, Manoni E, Mantovani G, Mariani V, Menichelli M, Rossi A, Santocchia A, Spiga D, Androsov K, Azzurri P, Bagliesi G, Bianchini L, Boccali T, Borrello L, Castaldi R, Ciocci MA, Dell'Orso R, Fedi G, Giannini L, Giassi A, Grippo MT, Ligabue F, Lomtadze T, Manca E, Mandorli G, Messineo A, Palla F, Rizzi A, Spagnolo P, Tenchini R, Tonelli G, Venturi A, Verdini PG, Barone L, Cavallari F, Cipriani M, Daci N, Del Re D, Di Marco E, Diemoz M, Gelli S, Longo E, Margaroli F, Marzocchi B, Meridiani P, Organtini G, Paramatti R, Preiato F, Rahatlou S, Rovelli C, Santanastasio F, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Bartosik N, Bellan R, Biino C, Cartiglia N, Cenna F, Costa M, Covarelli R, Degano A, Demaria N, Kiani B, Mariotti C, Maselli S, Migliore E, Monaco V, Monteil E, Monteno M, Obertino MM, Pacher L, Pastrone N, Pelliccioni M, Angioni GLP, Romero A, Ruspa M, Sacchi R, Shchelina K, Sola V, Solano A, Staiano A, Traczyk P, Belforte S, Casarsa M, Cossutti F, Della Ricca G, Zanetti A, Kim DH, Kim GN, Kim MS, Lee J, Lee S, Lee SW, Moon CS, Oh YD, Sekmen S, Son DC, Yang YC, Kim H, Moon DH, Oh G, Cifuentes JAB, Goh J, Kim TJ, Cho S, Choi S, Go Y, Gyun D, Ha S, Hong B, Jo Y, Kim Y, Lee K, Lee KS, Lim J, Park SK, Roh Y, Almond J, Kim J, Kim JS, Lee H, Nam K, Oh SB, Radburn-Smith BC, Seo SH, Yang UK, Yoo HD, Yu GB, Kim JH, Lee JSH, Park IC, Choi Y, Hwang C, Yu I, Dudenas V, Juodagalvis A, Vaitkus J, Ahmed I, Ibrahim ZA, Ali MABM, Idris FM, Abdullah WATW, Yusli MN, Zolkapli Z, Duran-Osuna MC, Castilla-Valdez H, De La Cruz-Burelo E, Ramirez-Sanchez G, Heredia-De La Cruz I, Rabadan-Trejo RI, Lopez-Fernandez R, Guisao JM, Reyes-Almanza R, Sanchez-Hernandez A, Moreno SC, Barrera CO, Valencia FV, Eysermans J, Pedraza I, Ibarguen HAS, Estrada CU, Pineda AM, Krofcheck D, Butler PH, Ahmad A, Hassan Q, Hoorani HR, Saddique A, Shah MA, Shoaib M, Waqas M, Bialkowska H, Bluj M, Boimska B, Frueboes T, Gorski M, Kazana M, Nawrocki K, Szleper M, Zalewski P, Bunkowski K, Byszuk A, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Olszewski M, Pyskir A, Walczak M, Bargassa P, Silva CBDE, Di Francesco A, Faccioli P, Galinhas B, Gallinaro M, Hollar J, Leonardo N, Iglesias LL, Nemallapudi MV, Seixas J, Strong G, Toldaiev O, Vadruccio D, Varela J, Afanasiev S, Bunin P, Gavrilenko M, Golutvin I, Gorbunov I, Kamenev A, Karjavin V, Lanev A, Malakhov A, Matveev V, Moisenz P, Palichik V, Perelygin V, Shmatov S, Shulha S, Skatchkov N, 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Elliott-Peisert A, Everaerts P, Fallavollita F, Franzoni G, Fulcher J, Funk W, Gigi D, Gilbert A, Gill K, Glege F, Gulhan D, Hegeman J, Innocente V, Jafari A, Janot P, Karacheban O, Kieseler J, Knunz V, Kornmayer A, Kortelainen MJ, Krammer M, Lange C, Lecoq P, Lourenco C, Lucchini MT, Malgeri L, Mannelli M, Martelli A, Meijers F, Merlin JA, Mersi S, Meschi E, Milenovic P, Moortgat F, Mulders M, Neugebauer H, Ngadiuba J, Orfanelli S, Orsini L, Pape L, Perez E, Peruzzi M, Petrilli A, Petrucciani G, Pfeiffer A, Pierini M, Pitters FM, Rabady D, Racz A, Reis T, Rolandi G, Rovere M, Sakulin H, Schafer C, Schwick C, Seidel M, Selvaggi M, Silva P, Sphicas P, Stakia A, Steggemann J, Stoye M, Tosi M, Treille D, Tsirou A, Veckalns V, Verweij M, Zeuner WD, Bertl W, Caminada L, Deiters K, Erdmann W, Horisberger R, Ingram Q, Kaestli HC, Kotlinski D, Langenegger U, Rohe T, Wiederkehr SA, Backhaus M, Bani L, Berger P, Casal B, Dissertori G, Dittmar M, Donega M, Dorfer C, Grab C, Heidegger C, Hits D, Hoss J, Kasieczka G, Klijnsma T, Lustermann W, Mangano B, Marionneau M, Meinhard MT, Meister D, Micheli F, Musella P, Nessi-Tedaldi F, Pandolfi F, Pata J, Pauss F, Perrin G, Perrozzi L, Quittnat M, Reichmann M, Becerra DAS, Schonenberger M, Shchutska L, Tavolaro VR, Theofilatos K, Olsson MLV, Wallny R, Zhu DH, Aarrestad TK, Amsler C, Canelli MF, De Cosa A, Del Burgo R, Donato S, Galloni C, Hreus T, Kilminster B, Pinna D, Rauco G, Robmann P, Salerno D, Schweiger K, Seitz C, Takahashi Y, Zucchetta A, Candelise V, Chang YH, Cheng KY, Doan TH, Jain S, Khurana R, Kuo CM, Lin W, Pozdnyakov A, Yu SS, Chang P, Chao Y, Chen KF, Chen PH, Fiori F, Hou WS, Hsiung Y, Kumar A, Liu YF, Lu RS, Paganis E, Psallidas A, Steen A, Tsai JF, Asavapibhop B, Kovitanggoon K, Singh G, Srimanobhas N, Bakirci MN, Bat A, Boran F, Damarseckin S, Demiroglu ZS, Dozen C, Eskut E, Girgis S, Gokbulut G, Guler Y, Hos I, Kangal EE, Kara O, Kiminsu U, Oglakci M, Onengut G, Ozdemir K, Ozturk S, Polatoz A, Cerci DS, Tok UG, Turkcapar S, Zorbakir IS, Zorbilmez C, Karapinar G, Ocalan K, Yalvac M, Zeyrek M, Gulmez E, Kaya M, Kaya O, Tekten S, Yetkin EA, Agaras MN, Atay S, Cakir A, Cankocak K, Komurcu Y, Grynyov B, Levchuk L, Ball F, Beck L, Brooke JJ, Burns D, Clement E, Cussans D, Davignon O, Flacher H, Goldstein J, Heath GP, Heath HF, Kreczko L, Newbold DM, Paramesvaran S, Sakuma T, El Nasr-storey SS, Smith D, Smith VJ, Brew C, Brown RM, Calligaris L, Cieri D, Cockerill DJA, Coughlan JA, Harder K, Harper S, Linacre J, Olaiya E, Petyt D, Shepherd-Themistocleous CH, Thea A, Tomalin IR, Williams T, Womersley WJ, Auzinger G, Bainbridge R, Bloch P, Borg J, Breeze S, Buchmuller O, Bundock A, Casasso S, Citron M, Colling D, Corpe L, Dauncey P, Davies G, Della Negra M, Di Maria R, Haddad Y, Hall G, Iles G, James T, Lane R, Laner C, Lyons L, Magnan AM, Malik S, Mastrolorenzo L, Matsushita T, Nash J, Nikitenko A, Palladino V, Pesaresi M, Raymond DM, Richards A, Rose A, Scott E, Seez C, Shtipliyski A, Summers S, Tapper A, Uchida K, Acosta MV, Virdee T, Wardle N, Winterbottom D, Wright J, Zenz SC, Cole JE, Hobson PR, Khan A, Kyberd P, Morton A, Reid ID, Teodorescu L, Zahid S, Borzou A, Call K, Dittmann J, Hatakeyama K, Liu H, Pastika N, Smith C, Bartek R, Dominguez A, Buccilli A, Cooper SI, Henderson C, Rumerio P, West C, Arcaro D, Avetisyan A, Bose T, Gastler D, Rankin D, Richardson C, Rohlf J, Sulak L, Zou D, Benelli G, Cutts D, Hadley M, Hakala J, Heintz U, Hogan JM, Kwok KHM, Laird E, Landsberg G, Mao Z, Narain M, Pazzini J, Piperov S, Sagir S, Syarif R, Yu D, Band R, Brainerd C, Breedon R, Sanchez MCD, Chertok M, Conway J, Conway R, Cox PT, Erbacher R, Flores C, Funk G, Ko W, Lander R, Mclean C, Mulhearn M, Pellett D, Pilot J, Shalhout S, Shi M, Smith J, Stolp D, Taylor D, Tos K, Tripathi M, Bachtis M, Bravo C, Cousins R, Dasgupta A, Florent A, Hauser J, Ignatenko M, Mccoll N, Regnard S, Saltzberg D, Schnaible C, Valuev V, Bouvier E, Burt K, Clare R, Ellison J, Gary JW, Shirazi SMAG, Hanson G, Karapostoli G, Kennedy E, Lacroix F, Long OR, Negrete MO, Paneva MI, Si W, Wang L, Wei H, Wimpenny S, Yates BR, Branson JG, Cittolin S, Derdzinski M, Gerosa R, Gilbert D, Hashemi B, Holzner A, Klein D, Kole G, Krutelyov V, Letts J, Masciovecchio M, Olivito D, Padhi S, Pieri M, Sani M, Sharma V, Simon S, Tadel M, Vartak A, Wasserbaech S, Wood J, Wurthwein F, Yagil A, Della Porta GZ, Amin N, Bhandari R, Bradmiller-Feld J, Campagnari C, Dishaw A, Dutta V, Sevilla MF, Gouskos L, Heller R, Incandela J, Ovcharova A, Qu H, Richman J, Stuart D, Suarez I, Yoo J, Anderson D, Bornheim A, Bunn J, Dutta I, Lawhorn JM, Newman HB, Nguyen TQ, Pena C, Spiropulu M, Vlimant JR, Wilkinson R, Xie S, Zhang Z, Zhu RY, Andrews MB, Ferguson T, Mudholkar T, Paulini M, Russ J, Sun M, Vogel H, Vorobiev I, Weinberg M, Cumalat JP, Ford WT, Jensen F, Johnson A, Krohn M, Leontsinis S, Macdonald E, Mulholland T, Stenson K, Wagner SR, Alexander J, Chaves J, Cheng Y, Chu J, Dittmer S, Mcdermott K, Mirman N, Patterson JR, Quach D, Rinkevicius A, Ryd A, Skinnari L, Soffi L, Tan SM, Tao Z, Thom J, Tucker J, Wittich P, Zientek M, Abdullin S, Albrow M, Alyari M, Apollinari G, Apresyan A, Apyan A, Bauerdick LAT, Beretvas A, Berryhill J, Bhat PC, Bolla G, Burkett K, Butler JN, Canepa A, Cerati GB, Cheung HWK, Chlebana F, Cremonesi M, Duarte J, Elvira VD, Freeman J, Gecse Z, Gottschalk E, Gray L, Green D, Grunendahl S, Gutsche O, Hanlon J, Harris RM, Hasegawa S, Hirschauer J, Hu Z, Jayatilaka B, Jindariani S, Johnson M, Joshi U, Klima B, Kreis B, Lammel S, Lincoln D, Lipton R, Liu M, Liu T, De Sa RL, Lykken J, Maeshima K, Magini N, Marraffino JM, Mason D, McBride P, Merkel P, Mrenna S, Nahn S, O'Dell V, Pedro K, Prokofyev O, Rakness G, Ristori L, Savoy-Navarro A, Schneider B, Sexton-Kennedy E, Soha A, Spalding WJ, Spiegel L, Stoynev S, Strait J, Strobbe N, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vernieri C, Verzocchi M, Vidal R, Wang M, Weber HA, Whitbeck A, Wu W, Acosta D, Avery P, Bortignon P, Bourilkov D, Brinkerhoff A, Carnes A, Carver M, Curry D, Field RD, Furic IK, Gleyzer SV, Joshi BM, Konigsberg J, Korytov A, Kotov K, Ma P, Matchev K, Mei H, Mitselmakher G, Shi K, Sperka D, Terentyev N, Thomas L, Wang J, Wang S, Yelton J, Joshi YR, Linn S, Markowitz P, Rodriguez JL, Ackert A, Adams T, Askew A, Hagopian S, Hagopian V, Johnson KF, Kolberg T, Martinez G, Perry T, Prosper H, Saha A, Santra A, Yohay R, Baarmand MM, Bhopatkar V, Colafranceschi S, Hohlmann M, Noonan D, Roy T, Yumiceva F, Adams MR, Apanasevich L, Berry D, Betts RR, Cavanaugh R, Chen X, Evdokimov O, Gerber CE, Hangal DA, Hofman DJ, Jung K, Kamin J, Gonzalez IDS, Tonjes MB, Trauger H, Varelas N, Wang H, Wu Z, 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, Blumenfeld B, Cocoros A, Eminizer N, Fehling D, Feng L, Gritsan AV, Maksimovic P, Roskes J, Sarica U, Swartz M, Xiao M, You C, Al-bataineh A, Baringer P, Bean A, Boren S, Bowen J, Castle J, Khalil S, Kropivnitskaya A, Majumder D, Mcbrayer W, Murray M, Rogan C, Royon C, Sanders S, Schmitz E, Takaki JDT, Wang Q, Ivanov A, Kaadze K, Maravin Y, Mohammadi A, Saini LK, Skhirtladze N, Rebassoo F, Wright D, Baden A, Baron O, Belloni A, Eno SC, Feng Y, Ferraioli C, Hadley NJ, Jabeen S, Jeng GY, Kellogg RG, Kunkle J, Mignerey AC, Ricci-Tam F, Shin YH, Skuja A, Tonwar SC, Abercrombie D, Allen B, Azzolini V, Barbieri R, Baty A, Bauer G, Bi R, Brandt S, Busza W, Cali IA, D'Alfonso M, Demiragli Z, Ceballos GG, Goncharov M, Harris P, Hsu D, Hu M, Iiyama Y, Innocenti GM, Klute M, Kovalskyi D, Lee YJ, Levin A, Luckey PD, Maier B, 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, Velicanu D, Wang TW, Wyslouch B, Benvenuti AC, Chatterjee RM, Evans A, Hansen P, Hiltbrand J, Kalafut S, Kubota Y, Lesko Z, Mans J, Nourbakhsh S, Ruckstuhl N, Rusack R, Turkewitz J, Wadud MA, Acosta JG, Oliveros S, Avdeeva E, Bloom K, Claes DR, Fangmeier C, Golf F, Suarez RG, Kamalieddin R, Kravchenko I, Monroy J, Siado JE, Snow GR, Stieger B, Dolen J, Godshalk A, Harrington C, Iashvili I, Nguyen D, Parker A, Rappoccio S, Roozbahani B, Alverson G, Barberis E, Freer C, Hortiangtham A, Massironi A, Morse DM, Orimoto T, De Lima RT, Wamorkar T, Wang B, Wisecarver A, Wood D, Charaf O, Hahn KA, Mucia N, Odell N, Schmitt MH, Sung K, Trovato M, Velasco M, Bucci R, Dev N, Hildreth M, Anampa KH, Jessop C, Karmgard DJ, Kellams N, Lannon K, Li W, Loukas N, Marinelli N, Meng F, Mueller C, Musienko Y, Planer M, Reinsvold A, Ruchti R, Siddireddy P, Smith G, Taroni S, Wayne M, Wightman A, Wolf M, Woodard A, Alimena J, Antonelli L, Bylsma B, Durkin LS, Flowers S, Francis B, Hart A, Hill C, Ji W, Ling TY, Liu B, Luo W, Winer BL, Wulsin HW, Cooperstein S, Driga O, Elmer P, Hardenbrook J, Hebda P, Higginbotham S, Kalogeropoulos A, Lange D, Luo J, Marlow D, Mei K, Ojalvo I, Olsen J, Palmer C, Piroue P, Stickland D, Tully C, Norberg S, Barker A, Barnes VE, Das S, Folgueras S, Gutay L, Jones M, Jung AW, Khatiwada A, Miller DH, Neumeister N, Peng CC, Qiu H, Schulte JF, Sun J, Wang F, Xiao R, Xie W, Cheng T, Parashar N, Stupak J, Chen Z, Ecklund KM, Freed S, Geurts FJM, Guilbaud M, Kilpatrick M, Michlin B, Padley BP, Roberts J, Rorie J, Shi W, Tu Z, Zabel J, Zhang A, Bodek A, de Barbaro P, Demina R, Duh YT, Ferbel T, Galanti M, Garcia-Bellido A, Han J, Hindrichs O, Khukhunaishvili A, Lo KH, Tan P, Verzetti M, Ciesielski R, Goulianos K, Mesropian C, Agapitos A, Chou JP, Gershtein Y, Espinosa TAG, Halkiadakis E, Heindl M, Hughes E, Kaplan S, Elayavalli RK, Kyriacou S, Lath A, Montalvo R, Nash K, Osherson M, Saka H, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Delannoy AG, Heideman J, 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, Mueller R, Pakhotin Y, Patel R, Perloff A, Pernie L, Rathjens D, Safonov A, Tatarinov A, Ulmer KA, Akchurin N, Damgov J, De Guio F, Dudero PR, Faulkner J, Gurpinar E, Kunori S, Lamichhane K, Mengke T, Muthumuni S, Peltola T, Undleeb S, Volobouev I, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Melo A, Ni H, Padeken K, Sheldon P, Tuo S, Velkovska J, Xu Q, Arenton MW, Barria P, Cox B, Hirosky R, Joyce M, Ledovskoy A, Li H, Neu C, Sinthuprasith T, Wolfe E, Xia F, Harr R, Karchin PE, Poudyal N, Sturdy J, Thapa P, Zaleski S, Brodski M, Buchanan J, Caillol C, Carlsmith D, Dasu S, Dodd L, Duric S, Gomber B, Grothe M, Herndon M, Herve A, Hussain U, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Rekovic V, Ruggles T, Savin A, Smith N, Smith WH, Woods N
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Observation of Medium-Induced Modifications of Jet Fragmentation in Pb-Pb Collisions at root s(NN)=5.02 TeV Using Isolated Photon-Tagged Jets

PHYSICAL REVIEW LETTERS 2018 DEC 14; 121(24):? Article 242301
Measurements of fragmentation functions for jets associated with an isolated photon are presented for the first time in pp and Pb-Pb collisions. The analysis uses data collected with the CMS detector at the CERN LHC at a nucleon-nucleon center-of-mass energy of 5.02 TeV. Fragmentation functions are obtained for jets with P-T(jet) 30 GeV/c in events containing an isolated photon with p(T)(gamma) 60 GeV/c, using charged tracks with transverse momentum p(T)(trk) > 1 GeV/c in a cone around the jet axis. The association with an isolated photon constrains the initial p(T) and azimuthal angle of the parton whose shower produced the jet. For central Pb-Pb collisions, modifications of the jet fragmentation functions are observed when compared to those measured in pp collisions, while no significant differences are found in the 50% most peripheral collisions. Jets in central Pb-Pb events show an excess (depletion) of low (high) p(T) particles, with a transition around 3 GeV/c. This measurement shows for the first time the in-medium shower modifications of partons (quark dominated) with well-defined initial kinematics. It constitutes a new well-controlled reference for testing theoretical models of the parton passage through the quark-gluon plasma.
Li SC, Li XH, Pope E, Stewart K, Higgins GC, Rabinovich CE, O'Neil KM, Haines KA, Laxer RM, Punaro M, Jacobe H, Andrews T, Wittkowski K, Nyirenda T, Foeldvari I, Torok KS
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New Features for Measuring Disease Activity in Pediatric Localized Scleroderma

JOURNAL OF RHEUMATOLOGY 2018 DEC 1; 45(12):1680-1688
Objective. To identify clinical features that define disease activity in pediatric localized scleroderma (LS), and determine their specificity and importance. Methods. We conducted a multicenter prospective study of patients with active and inactive LS skin lesions. A standardized evaluation of a single designated study lesion per subject was performed at 3 visits. We evaluated the pattern and correlation between assessed features and physician's global assessments of activity (PGA-A). Results. Ninety of 103 subjects had evaluable data; 66 had active and 24 inactive disease. Subjects had similar age of onset, sex, and disease patterns. Linear scleroderma was the most common subtype. Features specific for active disease included erythema, violaceous color, tactile warmth, abnormal skin texture, and disease extension. Scores for these variables changed over time and correlated with PGA-A of the lesion. Active and inactive lesions could not be distinguished by the presence or level of skin thickening, either of lesion edge or center. However, in active lesions, skin thickening scores did correlate with PGA-A scores. Regression analysis identified the combination of erythema, disease extension, violaceous color, skin thickening, and abnormal texture as predictive of PGA-A at study entry. Damage features were common irrespective of activity status. Conclusion. We identified variables strongly associated with disease activity, expanding upon those used in current measures, and determined their relative importance in physician activity scoring. Skin thickening was found to lack specificity for disease activity. These results will help guide development of a sensitive, responsive activity tool to improve care of patients with LS.
Black EM, Giunta S
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Repetitive Fragile Sites: Centromere Satellite DNA as a Source of Genome Instability in Human Diseases

GENES 2018 DEC; 9(12):? Article 615
Maintenance of an intact genome is essential for cellular and organismal homeostasis. The centromere is a specialized chromosomal locus required for faithful genome inheritance at each round of cell division. Human centromeres are composed of large tandem arrays of repetitive alpha-satellite DNA, which are often sites of aberrant rearrangements that may lead to chromosome fusions and genetic abnormalities. While the centromere has an essential role in chromosome segregation during mitosis, the long and repetitive nature of the highly identical repeats has greatly hindered in-depth genetic studies, and complete annotation of all human centromeres is still lacking. Here, we review our current understanding of human centromere genetics and epigenetics as well as recent investigations into the role of centromere DNA in disease, with a special focus on cancer, aging, and human immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome. We also highlight the causes and consequences of genomic instability at these large repetitive arrays and describe the possible sources of centromere fragility. The novel connection between alpha-satellite DNA instability and human pathological conditions emphasizes the importance of obtaining a truly complete human genome assembly and accelerating our understanding of centromere repeats' role in physiology and beyond.
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, 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, D'Errico M, Devoto F, Di Canto A, Di Ruzza B, Dittmann JR, Donati S, D'Onofrio M, Dorigo M, Driutti A, Ebina K, Edgar R, Elagin A, Erbacher R, Errede S, Esham B, Farrington S, Ramos JPF, Field R, Flanagan G, Forrest R, Franklin M, Freeman JC, Frisch H, Funakoshi Y, Galloni C, Garfinkel AF, Garosi P, Gerberich H, Gerchtein E, Giagu S, Giakoumopoulou V, Gibson K, Ginsburg CM, Giokaris N, Giromini P, 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, Grosso-Pilcher C, 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, Hussein M, 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 SH, Kim SB, Kim YJ, Kim YK, Kimura N, Kirby M, 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, Leo S, Leone S, Lewis JD, Limosani A, Lipeles E, Lister A, Liu Q, Liu T, Lockwitz S, Loginov A, Lucchesi D, Luca A, Lueck J, Lujan P, Lukens P, Lungu G, Lys J, Lysak R, Madrak R, Maestro P, Malik S, Manca G, Manousakis-Katsikakis A, Marchese L, Margaroli F, Marino P, Matera K, Mattson ME, Mazzacane A, Mazzanti P, McNulty R, Mehta A, Mehtala P, Mesropian C, Miao T, Michielin E, 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, Nigmanov T, Nodulman L, Noh SY, Norniella O, Oakes L, Oh SH, Oh YD, 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, Pranko A, Prokoshin F, Ptohos F, Punzi G, Fernandez IR, Renton P, Rescigno M, Rimondi F, Ristori L, Robson A, Rodriguez T, Rolli S, Ronzani M, Roser R, Rosner JL, Ruffini F, Ruiz A, Russ J, Rusu V, Sakumoto WK, Sakurai Y, Santi L, Sato K, Saveliev V, Savoy-Navarro A, Schlabach P, Schmidt EE, Schwarz T, Scodellaro L, Scuri F, Seidel S, Seiya Y, Semenov A, Sforza F, Shalhout SZ, Shears T, Shepard PF, Shimojima M, Shochet M, Shreyber-Tecker I, Simonenko A, Sliwa K, Smith JR, Snider FD, Song H, Sorin V, St Denis R, Stancari M, 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, Waters D, Wester WC, Whiteson D, Wicklund AB, Wilbur S, Williams HH, Wilson JS, Wilson P, Winer BL, Wittich P, Wolbers S, Wolfmeister 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 differential cross sections for W-boson production in association with jets in p(p)over-bar collisions at root s=1.96 TeV

PHYSICAL REVIEW D 2018 DEC 13; 98(11):? Article 112005
This paper presents a study of the production of a single W boson in association with one or more jets in proton-antiproton collisions at is root s = 1.96 TeV, using the entire data set collected in 2001-2011 by the Collider Detector at Fermilab at the Tevatron, which corresponds to an integrated luminosity of 9.0 fb(-1). The W boson is identified through its leptonic decays into electron and muon. The production cross sections are measured for each leptonic decay mode and combined after testing that the ratio of the W(-> mu v) + jets cross section to the W(-> ev) + jets cross section agrees with the hypothesis of e-mu lepton universality. The combination of measured cross sections, differential in the inclusive jet multiplicity (W + >= N jets with N = 1, 2, 3, or 4) and in the transverse energy of the leading jet, are compared with theoretical predictions.
Lu JH, Tang LC, Xu YQ, Ge KK, Huang JJ, Gu MG, Zhong J, Huang QS
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Mir-1287 suppresses the proliferation, invasion, and migration in hepatocellular carcinoma by targeting PIK3R3

JOURNAL OF CELLULAR BIOCHEMISTRY 2018 NOV; 119(11):9229-9238
Mature microRNAs (miRNAs) are a class of small noncoding RNA molecules involved in regulation of post-translational gene expression. Although aberrant levels of miRNAs have been found in various tumor tissues, their importance in tumor development and the molecular basis of their regulatory role remain unclear. Our bioinformatic analysis on The Cancer Genome Atlas database and microarray-based comparison of miRNA in different cell lines revealed that the level of mir-1287 is suppressed in hepatocellular carcinoma (HCC) cells. When upregulated, mir-1287 can reduce the tumorigenesis phenotypes of HCC cells in several in vitro models. We further found that mir-1287 directly targets messenger RNA encoding PIK3R3, which is a tumor-promoting factor acting in several pathways linked to tumorigenesis. Our study suggests that aberrant suppression of mir-1287 is potentially responsible for the development of HCC, and miRNA-based strategies may be developed for efficient detection and treatment of HCC.
Haselwandter CA, MacKinnon R
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Piezo's membrane footprint and its contribution to mechanosensitivity

ELIFE 2018 NOV 27; 7(?):? Article e41968
Piezo1 is an ion channel that gates open when mechanical force is applied to a cell membrane, thus allowing cells to detect and respond to mechanical stimulation. Molecular structures of Piezo1 reveal a large ion channel with an unusually curved shape. This study analyzes how such a curved ion channel interacts energetically with the cell membrane. Through membrane mechanical calculations, we show that Piezo1 deforms the membrane shape outside the perimeter of the channel into a curved 'membrane footprint'. This membrane footprint amplifies the sensitivity of Piezo1 to changes in membrane tension, rendering it exquisitely responsive. We assert that the shape of the Piezo channel is an elegant example of molecular form evolved to optimize a specific function, in this case tension sensitivity. Furthermore, the predicted influence of the membrane footprint on Piezo gating is consistent with the demonstrated importance of membrane-cytoskeletal attachments to Piezo gating.
Botkin JR, Appelbaum PS, Bakken S, Brown C, Burke W, Fabsitz R, Gamble VN, Gonsalves G, Kost R, Leonard DGB, McGuire A, Nichols JH, Patrick-Lake B, Wilkins CH, Zikmund-Fisher BJ
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Standardizing return of participant results

SCIENCE 2018 NOV 16; 362(6416):759-760
As members of the National Academies of Sciences, Engineering, and Medicine committee that wrote the report on the return of individual research results (1), we reject the allegations in the Policy Forum “Return of results and data to study participants” (S. M. Wolf and B. J. Evans, 12 October, p. 159) that the report is paternalistic, misunderstands the law, burdens Institutional Review Boards (IRBs), and creates barriers to the return of results.