Publications search
Found 37443 matches. Displaying 1101-1110
Niu YM, Tao X, Vaisey G, Olinares PDB, Alwaseem H, Chait BT, MacKinnon R
Show All Authors
Analysis of the mechanosensor channel functionality of TACAN (opens in new window)
ELIFE 2021 AUG 10; 10(?):? Article e71188
Mechanosensitive ion channels mediate transmembrane ion currents activated by mechanical forces. A mechanosensitive ion channel called TACAN was recently reported. We began to study TACAN with the intent to understand how it senses mechanical forces and functions as an ion channel. Using cellular patch-recording methods, we failed to identify mechanosensitive ion channel activity. Using membrane reconstitution methods, we found that TACAN, at high protein concentrations, produces heterogeneous conduction levels that are not mechanosensitive and are most consistent with disruptions of the lipid bilayer. We determined the structure of TACAN using single-particle cryo-electron microscopy and observed that it is a symmetrical dimeric transmembrane protein. Each protomer contains an intracellular-facing cleft with a coenzyme A cofactor, confirmed by mass spectrometry. The TACAN protomer is related in three-dimensional structure to a fatty acid elongase, ELOVL7. Whilst its physiological function remains unclear, we anticipate that TACAN is not a mechanosensitive ion channel.
Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, Ero J, Del Valle AE, Fruhwirth R, Jeitler M, Krammer N, Lechner L, Liko D, Madlener T, Mikulec I, Pitters FM, Rad N, Schieck J, Schofbeck R, Spanring M, Templ S, Waltenberger W, Wulz CE, Zarucki M, Chekhovsky V, Litomin A, Makarenko V, Gonzalez JS, Darwish MR, De Wolf EA, Di Croce D, Janssen X, Kello T, Lelek A, Pieters M, Sfar HR, Van Haevermaet H, Van Mechelen P, Van Putte S, Van Remortel N, Blekman F, Bols ES, Chhibra SS, D'Hondt J, De Clercq J, Lontkovskyi D, Lowette S, Marchesini I, Moortgat S, Morton A, Python Q, Tavernier S, Van Doninck W, Van Mulders P, Beghin D, Bilin B, Clerbaux B, De Lentdecker G, Delannoy H, Dorney B, Favart L, Grebenyuk A, Kalsi AK, Makarenko I, Moureaux L, Petre L, Popov A, Postiau N, Starling E, Thomas L, Vander Velde C, Vanlaer P, Vannerom D, Wezenbeek L, Cornelis T, Dobur D, Gruchala M, Khvastunov I, Niedziela M, Roskas C, Skovpen K, Tytgat M, Verbeke W, Vermassen B, Vit M, Bruno G, Bury F, Caputo C, David P, Delaere C, Delcourt M, Donertas IS, Giammanco A, Lemaitre V, Mondal K, Prisciandaro J, Taliercio A, Teklishyn M, Vischia P, Wuyckens S, Zobec J, Alves GA, Silva GC, Hensel C, Moraes A, Junior WLA, Das Chagas EBB, Malbouisson HB, Carvalho W, Chinellato J, Coelho E, Da Costa EM, Da Silveira GG, Damiao DD, De Souza SF, Martins J, Figueiredo DM, Jaime MM, De Almeida MM, Herrera CM, Mundim L, Nogima H, Teles PR, Rosas LJS, Santoro A, Do Amaral SMS, Sznajder A, Thiel M, Manganote EJT, De Araujo FTD, Pereira AV, Bernardes CA, Calligaris L, Tomei TRFP, Gregores EM, Lemos DS, Mercadante PG, Novaes SF, Padula SS, Aleksandrov A, Hadjiiska R, Iaydjiev P, Misheva M, Rodozov M, Shopova M, Sultanov G, Bonchev M, Dimitrov A, Ivanov T, Litov L, Pavlov B, Petkov P, Petrov A, Fang W, Guo Q, Wang H, Yuan L, Ahmad M, Hu Z, Wang Y, Chapon E, Chen GM, Chen HS, Chen M, Leggat D, Liao H, Liu Z, Sharma R, Spiezia A, Tao J, Thomas-wilsker J, Wang J, Zhang H, Zhang S, Zhao J, Agapitos A, Ban Y, Chen C, Levin A, Li J, Li Q, Lu M, Lyu X, Mao Y, Qian SJ, Wang D, Wang Q, Xiao J, You Z, Gao X, Xiao M, Avila C, Cabrera A, Florez C, Fraga J, Sarkar A, Delgado MAS, Jaramillo J, Guisao JM, Ramirez F, Alvarez JDR, Gonzalez CAS, Arbelaez NV, Giljanovic D, Godinovic N, Lelas D, Puljak I, Sculac T, Antunovic Z, Kovac M, Brigljevic V, Ferencek D, Majumder D, Mesic B, Roguljic M, Starodumov A, Susa T, Ather MW, Attikis A, Erodotou E, Ioannou A, Kole G, Kolosova M, Konstantinou S, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Saka H, Tsiakkouri D, Finger M, Finger M, Kveton A, Tomsa J, Ayala E, Jarrin EC, Abdelalim AA, Abu Zeid S, Khalil S, Mahmoud MA, Mohammed Y, Bhowmik S, De Oliveira ACA, Dewanjee RK, Ehataht K, Kadastik M, Raidal M, Veelken C, Eerola P, Kirschenmann H, Voutilainen M, Brucken E, Havukainen J, Karimaki V, Kim MS, Kinnunen R, Lampen T, Lassila-Perini K, Laurila S, Lehti S, Linden T, Siikonen H, Tuominen E, Tuominiemi J, Luukka P, Tuuva T, Besancon M, Couderc F, Dejardin M, Denegri D, Faure JL, Ferri F, Ganjour S, Givernaud A, Gras P, de Monchenault GH, Jarry P, Lenzi B, Locci E, Malcles J, Rander J, Rosowsky A, Sahin MO, Savoy-Navarro A, Titov M, Yu GB, Ahuja S, Amendola C, Beaudette F, Bonanomi M, Busson P, Charlot C, Davignon O, Diab B, Falmagne G, de Cassagnac RG, Hakimi A, Kucher I, Lobanov A, Perez CM, Nguyen M, Ochando C, Paganini P, Rembser J, Salerno R, Sauvan JB, Sirois Y, Zabi A, Zghiche A, Agram JL, Andrea J, Bloch D, Bourgatte G, Brom JM, Chabert EC, Collard C, Fontaine JC, Gele D, Goerlach U, Grimault C, Le Bihan AC, Van Hove P, Asilar E, Beauceron S, Bernet C, Boudoul G, Camen C, Carle A, Chanon N, Contardo D, Depasse P, El Mamouni H, Fay J, Gascon S, Gouzevitch M, Ille B, Jain S, Laktineh IB, Lattaud H, Lesauvage A, Lethuillier M, Mirabito L, Torterotot L, Touquet G, Vander Donckt M, Viret S, Toriashvili T, Tsamalaidze Z, Feld L, Klein K, Lipinski M, Meuser D, Pauls A, Preuten M, Rauch MP, Schulz J, Teroerde M, Eliseev D, Erdmann M, Fackeldey P, Fischer B, Ghosh S, Hebbeker T, Hoepfner K, Keller H, Mastrolorenzo L, Merschmeyer M, Meyer A, Millet P, Mocellin G, Mondal S, Mukherjee S, Noll D, Novak A, Pook T, Pozdnyakov A, Quast T, Radziej M, Rath Y, Reithler H, Roemer J, Schmidt A, Schuler SC, Sharma A, Wiedenbeck S, Zaleski S, Dziwok C, Flugge G, Ahmad WH, Hlushchenko O, Kress T, Nowack A, Pistone C, Pooth O, Roy D, Sert H, Stahl A, Ziemons T, Petersen HA, Martin MA, Asmuss P, Babounikau I, Baxter S, Behnke O, Martinez AB, Bin Anuar AA, Borras K, Botta V, Brunner D, Campbell A, Cardini A, Connor P, Rodriguez SC, Danilov V, De Wit A, Defranchis MM, Didukh L, Damiani DD, Eckerlin G, Eckstein D, Eichhorn T, Elwood A, Banos LIE, Gallo E, Geiser A, Giraldi A, Grohsjean A, Guthoff M, Harb A, Jafari A, Jomhari NZ, Jung H, Kasem A, Kasemann M, Kaveh H, Kleinwort C, Knolle J, Krucker D, Lange W, Lenz T, Lidrych J, Lipka K, Lohmann W, Mankel R, Melzer-Pellmann IA, Metwally J, Meyer AB, Meyer M, Missiroli M, Mnich J, Mussgiller A, Myronenko V, Otarid Y, Adan DP, Pflitsch SK, Pitzl D, Raspereza A, Saggio A, Saibel A, Savitskyi M, Scheurer V, Schutze P, Schwanenberger C, Shevchenko R, Singh A, Ricardo RES, Tholen H, Tonon N, Turkot O, Vagnerini A, Van de Klundert M, Walsh R, Walter D, Wen Y, Wichmann K, Wissing C, Wuchterl S, Zenaiev O, Zlebcik R, Aggleton R, Bein S, Benato L, Benecke A, De Leo K, Dreyer T, Ebrahimi A, Feindt F, Frohlich A, Garbers C, Garutti E, Gunnellini P, Haller J, Hinzmann A, Karavdina A, Kasieczka G, Klanner R, Kogler R, Kutzner V, Lange J, Lange T, Malara A, Multhaup J, Niemeyer CEN, Nigamova A, Rodriguez KJP, Rieger O, Schleper P, Schumann S, Schwandt J, Schwarz D, Sonneveld J, Stadie H, Steinbruck G, Vormwald B, Zoi I, Baselga M, Baur S, Bechtel J, Berger T, Butz E, Caspart R, Chwalek T, De Boer W, Dierlamm A, Droll A, El Morabit K, Faltermann N, Floh K, Giffels M, Gottmann A, Hartmann F, Heidecker C, Husemann U, Iqbal MA, Katkov I, Keicher P, Koppenhofer R, Maier S, Metzler M, Mitra S, Mozer MU, Muller D, Muller T, Musich M, Quast G, Rabbertz K, Rauser J, Savoiu D, Schafer D, Schnepf M, Schroder M, Seith D, Shvetsov I, Simonis HJ, Ulrich R, Wassmer M, Weber M, Wohrmann C, Wolf R, Wozniewski S, Anagnostou G, Asenov P, Daskalakis G, Geralis T, Kyriakis A, Loukas D, Paspalaki G, Stakia A, Diamantopoulou M, Karasavvas D, Karathanasis G, Kontaxakis P, Koraka CK, Manousakis-katsikakis A, Panagiotou A, Papavergou I, Saoulidou N, Theofilatos K, Vellidis K, Vourliotis E, Bakas G, Kousouris K, Papakrivopoulos I, Tsipolitis G, Zacharopoulou A, Evangelou I, Foudas C, Gianneios P, Katsoulis P, Kokkas P, Mallios S, Manitara K, Manthos N, Papadopoulos I, Strologas J, Bartok M, Chudasama R, Gadallah MMA, Lokos S, Major P, Mandal K, Mehta A, Pasztor G, Suranyi O, Veres GI, Bencze G, Hajdu C, Horvath D, Sikler F, Veszpremi V, Vesztergombi G, Czellar S, Karancsi J, Molnar J, Szillasi Z, Teyssier D, Raics P, Trocsanyi ZL, Ujvari B, Choudhury S, Komaragiri JR, Kumar D, Panwar L, Tiwari PC, Bahinipati S, Dash D, Kar C, Mal P, Mishra T, Bindhu VKMN, Nayak A, Sahoo DK, Sur N, Swain SK, Bansal S, Beri SB, Bhatnagar V, Chauhan S, Dhingra N, Gupta R, Kaur A, Kaur S, Kumari P, Lohan M, Meena M, Sandeep K, Sharma S, Singh JB, Virdi AK, Ahmed A, Bhardwaj A, Choudhary BC, Garg RB, Gola M, Keshri S, Kumar A, Naimuddin M, Priyanka P, Ranjan K, Shah A, Bharti M, Bhattacharya R, Bhattacharya S, Bhowmik D, Dutta S, Ghosh S, Gomber B, Maity M, Nandan S, Palit P, Purohit A, Rout PK, Saha G, Sarkar S, Sharan M, Singh B, Thakur S, Behera PK, Behera SC, Kalbhor P, Muhammad A, Pradhan R, Pujahari PR, Sharma A, Sikdar AK, Dutta D, Jha V, Kumar V, Mishra DK, Naskar K, Netrakanti PK, Pant LM, Shukla P, Aziz T, Bhat MA, Dugad S, Verma RK, Sarkar U, Banerjee S, Bhattacharya S, Chatterjee S, Das P, Guchait M, Karmakar S, Kumar S, Majumder G, Mazumdar K, Mukherjee S, Roy D, Sahoo N, Dube S, Kansal B, Kapoor A, Kothekar K, Pandey S, Rane A, Rastogi A, Sharma S, Bakhshiansohi H, Chenarani S, Etesami SM, Khakzad M, Najafabadi MM, Felcini M, Grunewald M, Abbrescia M, Aly R, Aruta C, Colaleo A, Creanza D, De Filippis N, De Palma M, Di Florio A, Di Pilato A, Elmetenawee W, Fiore L, Gelmi A, Gul M, Iaselli G, Ince M, Lezki S, Maggi G, Maggi M, Margjeka I, Merlin JA, My S, Nuzzo S, Pompili A, Pugliese G, Ranieri A, Selvaggi G, Silvestris L, Simone FM, Venditti R, Verwilligen P, Abbiendi G, Battilana C, Bonacorsi D, Borgonovi L, Braibant-Giacomelli S, Campanini R, Capiluppi P, Castro A, Cavallo FR, Ciocca C, Cuffiani M, Dallavalle GM, Diotalevi T, Fabbri F, Fanfani A, Fontanesi E, Giacomelli P, Giommi L, Grandi C, Guiducci L, Iemmi F, Lo Meo S, Marcellini S, Masetti G, Navarria FL, Perrotta A, Primavera F, Rovelli T, Siroli GP, Tosi N, Albergo S, Costa S, Di Mattia A, Potenza R, Tricomi A, Tuve C, Barbagli G, Cassese A, Ceccarelli R, Ciulli V, Civinini C, D'Alessandro R, Fiori F, Focardi E, Latino G, Lenzi P, Lizzo M, Meschini M, Paoletti S, Seidita R, Sguazzoni G, Viliani L, Benussi L, Bianco S, Piccolo D, Ferro F, Mulargia R, Robutti E, Tosi S, Benaglia A, Beschi A, Brivio F, Cetorelli F, Ciriolo V, De Guio F, Dinardo ME, Dini P, Gennai S, Ghezzi A, Govoni P, Guzzi L, Malberti M, Malvezzi S, Menasce D, Monti F, Moroni L, Paganoni M, Pedrini D, Ragazzi S, de Fatis TT, Valsecchi D, Zuolo D, Buontempo S, Cavallo N, De Iorio A, Fabozzi F, Fienga F, Iorio AOM, Layer L, Lista L, Meola S, Paolucci P, Rossi B, Sciacca C, Voevodina E, Azzi P, Bacchetta N, Bisello D, Boletti A, Bragagnolo A, Carlin R, Checchia P, Manzano PD, Dorigo T, Gasparini F, Gasparini U, Hoh SY, Margoni M, Meneguzzo AT, Presilla M, Ronchese P, Rossin R, Simonetto F, Strong G, Tiko A, Tosi M, Zanetti M, Zotto P, Zucchetta A, Zumerle G, Braghieri A, Calzaferri S, Fiorina D, Montagna P, Ratti SP, Re V, Ressegotti M, Riccardi C, Salvini P, Vai I, Vitulo P, Biasini M, Bilei GM, Ciangottini D, Fano L, Lariccia P, Mantovani G, Mariani V, Menichelli M, Moscatelli F, Rossi A, Santocchia A, Spiga D, Tedeschi T, Androsov K, Azzurri P, Bagliesi G, Bertacchi V, Bianchini L, Boccali T, Castaldi R, Ciocci MA, Dell'Orso R, Di Domenico MR, Donato S, Giannini L, Giassi A, Grippo MT, Ligabue F, Manca E, Mandorli G, Messineo A, Palla F, Ramirez-Sanchez G, Rizzi A, Rolandi G, Chowdhury SR, Shafiei N, Spagnolo P, Tenchini R, Tonelli G, Venturi A, Verdini PG, Cavallari F, Cipriani M, Del Re D, Di Marco E, Diemoz M, Longo E, Meridiani P, Organtini G, Pandolfi F, Paramatti R, Quaranta C, Rahatlou S, Rovelli C, Santanastasio F, Soffi L, Tramontano R, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Bartosik N, Bellan R, Bellora A, Biino C, Cappati A, Cartiglia N, Cometti S, Costa M, Covarelli R, Demaria N, Kiani B, Legger F, Mariotti C, Maselli S, Migliore E, Monaco V, Monteil E, Monteno M, Obertino MM, Ortona G, Pacher L, Pastrone N, Pelliccioni M, Angioni GLP, Ruspa M, Salvatico R, Siviero F, Sola V, Solano A, Soldi D, Staiano A, Trocino D, Belforte S, Candelise V, Casarsa M, Cossutti F, Da Rold A, Della Ricca G, Vazzoler F, Dogra S, Huh C, Kim B, Kim DH, Kim GN, Lee J, Lee SW, Moon CS, Oh YD, Pak SI, Sekmen S, Yang YC, Kim H, Moon DH, Francois B, Kim TJ, Park J, Cho S, Choi S, Go Y, Ha S, Hong B, Lee K, Lee KS, Lim J, Park J, Park SK, Yoo J, Goh J, Gurtu A, Kim HS, Kim Y, Almond J, Bhyun JH, Choi J, Jeon S, Kim J, Kim JS, Ko S, Kwon H, Lee H, Lee K, Lee S, Nam K, Oh BH, Oh M, Oh SB, Radburn-Smith BC, Seo H, Yang UK, Yoon I, Jeon D, Kim JH, Ko B, Lee JSH, Park IC, Roh Y, Song D, Watson IJ, Yoo HD, Choi Y, Hwang C, Jeong Y, Lee H, Lee Y, Yu I, Maghrbi Y, Veckalns V, Juodagalvis A, Rinkevicius A, Tamulaitis G, Abdullah WATW, Yusli MN, Zolkapli Z, Benitez JF, Hernandez AC, Quijada JAM, Palomo LV, Castilla-Valdez H, De La Cruz-Burelo E, Heredia-De La Cruz I, Lopez-Fernandez R, Sanchez-Hernandez A, Moreno SC, Barrera CO, Ramirez-Garcia M, Valencia FV, Eysermans J, Pedraza I, Ibarguen HAS, Estrada CU, Pineda AM, Mijuskovic J, Raicevic N, Krofcheck D, Bheesette S, Butler PH, Ahmad A, Asghar MI, Awan MIM, Hassan Q, Hoorani HR, Khan WA, Shah MA, Shoaib M, Waqas M, Bialkowska H, Bluj M, Boimska B, Frueboes T, Gorski M, Kazana M, Szleper M, Traczyk P, Zalewski P, Bunkowski K, Byszuk A, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Olszewski M, Walczak M, Araujo M, Bargassa P, Bastos D, Faccioli P, Gallinaro M, Hollar J, Leonardo N, Niknejad T, Seixas J, Shchelina K, Toldaiev O, Varela J, Afanasiev S, Baginyan A, Bunin P, Golunov A, Golutvin I, Gorbunov I, Kamenev A, Karjavine V, Kashunin I, Korenkov V, Lanev A, Malakhov A, Matveev V, Moisenz P, Palichik V, Perelygin V, Savina M, Shmatov S, Shulha S, Smirnov V, Teryaev O, Voytishin N, Zarubin A, Gavrilov G, Golovtcov V, Ivanov Y, Kim V, Kuznetsova E, Murzin V, Oreshkin V, Smirnov I, Sosnov D, Sulimov V, Uvarov L, Volkov S, Vorobyev A, Andreev Y, Dermenev A, Gninenko S, Golubev N, Karneyeu A, Kirsanov M, Krasnikov N, Pashenkov A, Pivovarov G, Tlisov D, Toropin A, Epshteyn V, Gavrilov V, Lychkovskaya N, Nikitenko A, Popov V, Pozdnyakov I, Safronov G, Spiridonov A, Stepennov A, Toms M, Vlasov E, Zhokin A, Aushev T, Bychkova O, Chadeeva M, Philippov D, Popova E, Rusinov V, Andreev V, Azarkin M, Dremin I, Kirakosyan M, Terkulov A, Belyaev A, Boos E, Ershov A, Gribushin A, Khein L, Klyukhin V, Kodolova O, Lokhtin I, Lukina O, Obraztsov S, Petrushanko S, Savrin V, Snigirev A, Blinov V, Dimova T, Kardapoltsev L, Ovtin I, Skovpen Y, Azhgirey I, Bayshev I, Kachanov V, Kalinin A, Konstantinov D, Petrov V, Ryutin R, Sobol A, Troshin S, Tyurin N, Uzunian A, Volkov A, Babaev A, Iuzhakov A, Okhotnikov V, Sukhikh L, Adzic P, Cirkovic P, Dordevic M, Milenovic P, Milosevic J, Aguilar-Benitez M, Maestre JA, Fernandez AA, Bachiller I, Luna MB, Bedoya CF, Cifuentes JAB, Montoya CAC, Cepeda M, Cerrada M, Colino N, De La Cruz B, Peris AD, Ramos JPF, Flix J, Fouz MC, Alonso AG, Lopez OG, Lopez SG, Hernandez JM, Tobar AN, Josa MI, Moran D, Yzquierdo APC, Pelayo JP, Redondo I, Romero L, Navas SS, Soares MS, Triossi A, Willmott C, Albajar C, de Troconiz JF, Reyes-Almanza R, Gonzalez BA, Cuevas J, Erice C, Menendez JF, Folgueras S, Caballero IG, Cortezon EP, Alvarez CR, Bouza VR, Cruz SS, Trapote A, Cabrillo IJ, Calderon A, Quero BC, Campderros JD, Fernandez M, Manteca PJF, Gomez G, Rivero CM, del Arbol PMR, Matorras F, Gomez JP, Prieels C, Ricci-Tam F, Rodrigo T, Ruiz-Jimeno A, Russo L, Scodellaro L, Vila I, Garcia JMV, Jayananda M, Kailasapathy B, Sonnadara DUJ, Wickramarathna D, Dharmaratna WGD, Liyanage K, Perera N, Wickramage N, Aarrestad TK, Abbaneo D, Akgun B, Auffray E, Auzinger G, Baillon P, Ball AH, Barney D, Bendavid J, Beni N, Bianco M, Bocci A, Bortignon P, Brondolin E, Camporesi T, Cerminara G, Cristella L, D'Enterria D, Dabrowski A, Daci N, Daponte V, David A, De Roeck A, Di Maria R, Dobson M, Dunser M, Dupont N, Elliott-Peisert A, Emriskova N, Fallavollita F, Fasanella D, Fiorendi S, Franzoni G, Fulcher J, Funk W, Gigi D, Gill K, Glege F, Gouskos L, Guilbaud M, Gulhan D, Haranko M, Hegeman J, Iiyama Y, Innocente V, James T, Janot P, Kieseler J, Komm M, Kratochwil N, Lange C, Lecoq P, Long K, Lourenco C, Malgeri L, Mannelli M, Massironi A, Meijers F, Mersi S, Meschi E, Moortgat F, Mulders M, Ngadiuba J, Niedziela J, Orfanelli S, Orsini L, Pantaleo F, Pape L, Perez E, Peruzzi M, Petrilli A, Petrucciani G, Pfeiffer A, Pierini M, Rabady D, Racz A, Rieger M, Rovere M, Sakulin H, Salfeld-Nebgen J, Scarfi S, Schafer C, Schwick C, Selvaggi M, Sharma A, Silva P, Sphicas P, Steggemann J, Summers S, Tavolaro VR, Treille D, Tsirou A, Van Onsem GP, Vartak A, Verzetti M, Wozniak KA, Zeuner WD, Caminada L, Erdmann W, Horisberger R, Ingram Q, Kaestli HC, Kotlinski D, Langenegger U, Rohe T, Backhaus M, Berger P, Calandri A, Chernyavskaya N, Dissertori G, Dittmar M, Donega M, Dorfer C, Gadek T, Espinosa TAG, Grab C, Hits D, Lustermann W, Lyon AM, Manzoni RA, Meinhard MT, Micheli F, Nessi-Tedaldi F, Pauss F, Perovic V, Perrin G, Perrozzi L, Pigazzini S, Ratti MG, Reichmann M, Reissel C, Reitenspiess T, Ristic B, Ruini D, Becerra DAS, Schonenberger M, Shchutska L, Stampf V, Olsson MLV, Wallny R, Zhu DH, Amsler C, Botta C, Brzhechko D, Canelli MF, De Cosa A, Del Burgo R, Heikkila JK, Huwiler M, Jofrehei A, Kilminster B, Leontsinis S, Macchiolo A, Meiring P, Mikuni VM, Molinatti U, Neutelings I, Rauco G, Reimers A, Robmann P, Schweiger K, Takahashi Y, Wertz S, Adloff C, Kuo CM, Lin W, Roy A, Sarkar T, Yu SS, Ceard L, Chang P, Chao Y, Chen KF, Chen PH, Hou WS, Li YY, Lu RS, Paganis E, Psallidas A, Steen A, Yazgan E, Asavapibhop B, Asawatangtrakuldee C, Srimanobhas N, Boran F, Damarseckin S, Demiroglu ZS, Dolek F, Dozen C, Dumanoglu I, Eskut E, Gokbulut G, Guler Y, Guler EG, Hos I, Isik C, Kangal EE, Kara O, Topaksu AK, Kiminsu U, Onengut G, Ozdemir K, Polatoz A, Simsek AE, Tali B, Tok UG, Turkcapar S, Zorbakir IS, Zorbilmez C, Isildak B, Karapinar G, Ocalan K, Yalvac M, Atakisi IO, Gulmez E, Kaya M, Kaya O, Tekten S, Yetkin EA, Cakir A, Cankocak K, Komurcu Y, Sen S, Sen FA, Cerci S, Ozkorucuklu S, Cerci DS, Grynyov B, Levchuk L, Bhal E, Bologna S, Brooke JJ, Clement E, Cussans D, Flacher H, Goldstein J, Heath GP, Heath HF, Kreczko L, Krikler B, Paramesvaran S, Sakuma T, El Nasr-Storey SS, Smith VJ, Taylor J, Titterton A, Bell KW, Belyaev A, Brew C, Brown RM, Cockerill DJA, Ellis KV, Harder K, Harper S, Linacre J, Manolopoulos K, Newbold DM, Olaiya E, Petyt D, Reis T, Schuh T, Shepherd-Themistocleous CH, Thea A, Tomalin IR, Williams T, Bainbridge R, Bloch P, Bonomally S, Borg J, Breeze S, Buchmuller O, Bundock A, Cepaitis V, Chahal GS, Colling D, Dauncey P, Davies G, Della Negra M, Everaerts P, Fedi G, Hall G, Iles G, Langford J, Lyons L, Magnan AM, Malik S, Martelli A, Milosevic V, Nash J, Palladino V, Pesaresi M, Raymond DM, Richards A, Rose A, Scott E, Seez C, Shtipliyski A, Stoye M, Tapper A, Uchida K, Virdee T, Wardle N, Webb SN, Winterbottom D, Zecchinelli AG, Zenz SC, Cole JE, Hobson PR, Khan A, Kyberd P, Mackay CK, Reid ID, Teodorescu L, Zahid S, Brinkerhoff A, Call K, Caraway B, Dittmann J, Hatakeyama K, Kanuganti AR, Madrid C, McMaster B, Pastika N, Sawant S, Smith C, Bartek R, Dominguez A, Uniyal R, Hernandez AMV, Buccilli A, Charaf O, Cooper SI, Gleyzer SV, Henderson C, Rumerio P, West C, Akpinar A, Albert A, Arcaro D, Cosby C, Demiragli Z, Gastler D, Richardson C, Rohlf J, Salyer K, Sperka D, Spitzbart D, Suarez I, Yuan S, Zou D, Benelli G, Burkle B, Coubez X, Cutts D, Duh YT, Hadley M, Heintz U, Hogan JM, Kwok KHM, Laird E, Landsberg G, Lau KT, Lee J, Narain M, Sagir S, Syarif R, Usai E, Wong WY, Yu D, Zhang W, Band R, Brainerd C, Breedon R, Sanchez MCD, Chertok M, Conway J, Conway R, Cox PT, Erbacher R, Flores C, Funk G, Jensen F, Ko W, Kukral O, Lander R, Mulhearn M, Pellett D, Pilot J, Shi M, Taylor D, Tos K, Tripathi M, Yao Y, Zhang F, Bachtis M, Cousins R, Dasgupta A, Florent A, Hamilton D, Hauser J, Ignatenko M, Lam T, Mccoll N, Nash WA, Regnard S, Saltzberg D, Schnaible C, Stone B, Valuev V, Burt K, Chen Y, Clare R, Gary JW, Shirazi SMAG, Hanson G, Karapostoli G, Long OR, Manganelli N, Negrete MO, Paneva MI, Si W, Wimpenny S, Zhang Y, Branson JG, Chang P, Cittolin S, Cooperstein S, Deelen N, Derdzinski M, Duarte J, Gerosa R, Gilbert D, Hashemi B, Klein D, Krutelyov V, Letts J, Masciovecchio M, May S, Padhi S, Pieri M, Sharma V, Tadel M, Wurthwein F, Yagil A, Amin N, Campagnari C, Citron M, Dorsett A, Dutta V, Incandela J, Marsh B, Mei H, Ovcharova A, Qu H, Quinnan M, Richman J, Sarica U, Stuart D, Wang S, Anderson D, Bornheim A, Cerri O, Dutta I, Lawhorn JM, Lu N, Mao J, Newman HB, Nguyen TQ, Pata J, Spiropulu M, Vlimant JR, Xie S, Zhang Z, Zhu RY, Alison J, Andrews MB, Ferguson T, Mudholkar T, Paulini M, Sun M, Vorobiev I, Cumalat JP, Ford WT, MacDonald E, Mulholland T, Patel R, Perloff A, Stenson K, Ulmer KA, Wagner SR, Alexander J, Cheng Y, Chu J, Cranshaw DJ, Datta A, Frankenthal A, Mcdermott K, Monroy J, Patterson JR, Quach D, Ryd A, Sun W, Tan SM, Tao Z, Thom J, Wittich P, Zientek M, Abdullin S, Albrow M, Alyari M, Apollinari G, Apresyan A, Apyan A, Banerjee S, Bauerdick LAT, Beretvas A, Berry D, Berryhill J, Bhat PC, Burkett K, Butler JN, Canepa A, Cerati GB, Cheung HWK, Chlebana F, Cremonesi M, Elvira VD, Freeman J, Gecse Z, Gottschalk E, Gray L, Green D, Grunendahl S, Gutsche O, Harris RM, Hasegawa S, Heller R, Herwig TC, Hirschauer J, Jayatilaka B, Jindariani S, Johnson M, Joshi U, Klijnsma T, Klima B, Kortelainen MJ, Lammel S, Lincoln D, Lipton R, Liu M, Liu T, Lykken J, Maeshima K, Mason D, McBride P, Merkel P, Mrenna S, Nahn S, O'Dell V, Papadimitriou V, Pedro K, Pena C, Prokofyev O, Ravera F, Hall AR, Ristori L, Schneider B, Sexton-Kennedy E, Smith N, Soha A, Spalding WJ, Spiegel L, Stoynev S, Strait J, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Wang M, Weber HA, Woodard A, Acosta D, Avery P, Bourilkov D, Cadamuro L, Cherepanov V, Errico F, Field RD, Guerrero D, Joshi BM, Kim M, Konigsberg J, Korytov A, Lo KH, Matchev K, Menendez N, Mitselmakher G, Rosenzweig D, Shi K, Wang J, Wang S, Zuo X, Joshi YR, Adams T, Askew A, Diaz D, Habibullah R, Hagopian S, Hagopian V, Johnson KF, Khurana R, Kolberg T, Martinez G, Prosper H, Schiber C, Yohay R, Zhang J, Baarmand MM, Butalla S, Elkafrawy T, Hohlmann M, Noonan D, Rahmani M, Saunders M, Yumiceva F, Adams MR, Apanasevich L, Gonzalez HB, Cavanaugh R, Chen X, Dittmer S, Evdokimov O, Gerber CE, Hangal DA, Hofman DJ, Mills C, Oh G, Roy T, Tonjes MB, Varelas N, Viinikainen J, Wang H, Wang X, Wu Z, Alhusseini M, Bilki B, Dilsiz K, Durgut S, Gandrajula RP, Haytmyradov M, Khristenko V, Koseyan OK, Merlo JP, Mestvirishvili A, Moeller A, Nachtman J, Ogul H, Onel Y, Ozok F, Penzo A, Snyder C, Tiras E, Wetzel J, Yi K, Amram O, Blumenfeld B, Corcodilos L, Eminizer M, Gritsan AV, Kyriacou S, Maksimovic P, Mantilla C, Roskes J, Swartz M, Vami TA, Baringer P, Bean A, Bylinkin A, Khalil S, King J, Krintiras G, Kropivnitskaya A, Murray M, Rogan C, Sanders S, Schmitz E, Takaki JDT, Wang Q, Wilson G, Duric S, Ivanov A, Kaadze K, Kim D, Maravin Y, Mendis DR, Mitchell T, Modak A, Mohammadi A, Rebassoo F, Wright D, Adams E, Baden A, Baron O, Belloni A, Eno SC, Feng Y, Hadley NJ, Jabeen S, Jeng GY, Kellogg RG, Koeth T, Mignerey AC, Nabili S, Seidel M, Skuja A, Tonwar SC, Wang L, Wong K, Abercrombie D, Allen B, Bi R, Brandt S, Busza W, Cali IA, Chen Y, D'Alfonso M, Ceballos GG, Goncharov M, Harris P, Hsu D, Hu M, Klute M, Kovalskyi D, Krupa J, Lee YJ, Luckey PD, Maier B, Marini AC, Mcginn C, Mironov C, Narayanan S, Niu X, Paus C, Rankin D, Roland C, Roland G, Shi Z, Stephans GSF, Sumorok K, Tatar K, Velicanu D, Wang J, Wang TW, Wang Z, Wyslouch B, Chatterjee RM, Evans A, Guts S, Hansen P, Hiltbrand J, Jain S, Krohn M, Kubota Y, Lesko Z, Mans J, Revering M, Rusack R, Saradhy R, Schroeder N, Strobbe N, Wadud MA, Acosta JG, Oliveros S, Bloom K, Chauhan S, Claes DR, Fangmeier C, Finco L, Golf F, Fernandez JRG, Kravchenko I, Siado JE, Snow GR, Stieger B, Tabb W, Agarwal G, Harrington C, Hay L, Iashvili I, Kharchilava A, McLean C, Nguyen D, Parker A, Pekkanen J, Rappoccio S, Roozbahani B, Alverson G, Barberis E, Freer C, Haddad Y, Hortiangtham A, Madigan G, Marzocchi B, Morse DM, Nguyen V, Orimoto T, Skinnari L, Tishelman-Charny A, Wamorkar T, Wang B, Wisecarver A, Wood D, Bhattacharya S, Bueghly J, Chen Z, Gilbert A, Gunter T, Hahn KA, Odell N, Schmitt MH, Sung K, Velasco M, Bucci R, Dev N, Goldouzian R, Hildreth M, Anampa KH, Jessop C, Karmgard DJ, Lannon K, Li W, Loukas N, Marinelli N, Mcalister I, Meng F, Mohrman K, Musienko Y, Ruchti R, Siddireddy P, Taroni S, Wayne M, Wightman A, Wolf M, Zygala L, Alimena J, Bylsma B, Cardwell B, Durkin LS, Francis B, Hill C, Lefeld A, Winer BL, Yates BR, Dezoort G, Elmer P, Greenberg B, Haubrich N, Higginbotham S, Kalogeropoulos A, Kopp G, Kwan S, Lange D, Lucchini MT, Luo J, Marlow D, Mei K, Ojalvo I, Olsen J, Palmer C, Piroue P, Stickland D, Tully C, Malik S, Norberg S, Barnes VE, Chawla R, Das S, Gutay L, Jones M, Jung AW, Mahakud B, Negro G, Neumeister N, Peng CC, Piperov S, Qiu H, Schulte JF, Trevisani N, Wang F, Xiao R, Xie W, Cheng T, Dolen J, Parashar N, Stojanovic M, Baty A, Dildick S, Ecklund KM, Freed S, Geurts FJM, Kilpatrick M, Kumar A, Li W, Padley BP, Redjimi R, Roberts J, Rorie J, Shi W, Leiton AGS, Zhang A, Bodek A, de Barbaro P, Demina R, Dulemba JL, Fallon C, Ferbel T, Galanti M, Garcia-Bellido A, Hindrichs O, Khukhunaishvili A, Ranken E, Taus R, Ciesielski R, Chiarito B, Chou JP, Gandrakota A, Gershtein Y, Halkiadakis E, Hart A, Heindl M, Hughes E, Kaplan S, Karacheban O, Laflotte I, Lath A, Montalvo R, Nash K, Osherson M, Salur S, Schnetzer S, Somalwar S, Stone R, Thayil SA, Thomas S, Acharya H, Delannoy AG, Spanier S, Bouhali O, Dalchenko M, Delgado A, Eusebi R, Gilmore J, Huang T, Kamon T, Kim H, Luo S, Malhotra S, Mueller R, Overton D, Pernie L, Rathjens D, Safonov A, Sturdy J, Akchurin N, Damgov J, Hegde V, Kunori S, Lamichhane K, Lee SW, Mengke T, Muthumuni S, Peltola T, Undleeb S, Volobouev I, Wang Z, Whitbeck A, Appelt E, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Melo A, Ni H, Padeken K, Romeo F, Sheldon P, Tuo S, Velkovska J, Verweij M, Ang L, Arenton MW, Cox B, Cummings G, Hakala J, Hirosky R, Joyce M, Ledovskoy A, Neu C, Tannenwald B, Wang Y, Wolfe E, Xia F, Karchin PE, Poudyal N, Thapa P, Black K, Bose T, Buchanan J, Caillol C, Dasu S, De Bruyn I, Galloni C, He H, Herndon M, Herve A, Hussain U, Lanaro A, Loeliger A, Loveless R, Sreekala JM, Mallampalli A, Pinna D, Ruggles T, Savin A, Shang V, Sharma V, Smith WH, Teague D, Trembath-reichert S, Vetens W, Antchev G, Aspell P, Atanassov I, Avati V, Baechler J, Barrera CB, Berardi V, Berretti M, Borchsh V, Bossini E, Bottigli U, Bozzo M, Burkhardt H, Cafagna FS, Catanesi MG, Csanad M, Deile M, De Leonardis F, Doubek M, Druzhkin D, Eggert K, Eremin V, Fiergolski A, Forthomme L, Garcia F, Georgiev V, Giani S, Grzanka L, Hammerbauer J, Isidori T, Ivanchenko V, Janda M, Karev A, Kaspar J, Kaynak B, Kopal J, Kundrat V, Lami S, Linhart R, Lindsey C, Losurdo L, Rodriguez FL, Macri M, Malawski M, Minafra N, Minutoli S, Naaranoja T, Nemes F, Niewiadomski H, Novak T, Oliveri E, Oljemark F, Oriunno M, Osterberg K, Palazzi P, Passaro V, Peroutka Z, Prochazka J, Quinto M, Radermacher E, Radicioni E, Ravotti F, Royon C, Ruggiero G, Saarikko H, Samoylenko VD, Scribano A, Siroky J, Smajek J, Snoeys W, Stefanovitch R, Sziklai J, Taylor C, Tcherniaev E, Turini N, Urban O, Vacek V, Vavroch O, Welti J, Williams J, Zich J, Zielinski K
Show All Authors
Hard color-singlet exchange in dijet events in proton-proton collisions at root s=13 TeV (opens in new window)
PHYSICAL REVIEW D 2021 AUG 26; 104(3):? Article 032009
Events where the two leading jets are separated by a pseudorapidity interval devoid of particle activity, known as jet-gap-jet events, are studied in proton-proton collisions at root s = 13 TeV. The signature is expected from hard color-singlet exchange. Each of the highest transverse momentum (p(T)) jets must have p(T)(jet) > 40 GeV and pseudorapidity 1.4 < vertical bar eta(jet)vertical bar < 4.7, with eta(jet1)eta(jet2) < 0, where jet1 and jet2 are the leading and subleading jets in p(T), respectively. The analysis is based on data collected by the CMS and TOTEM experiments during a low luminosity, high-beta* run at the CERN LHC in 2015, with an integrated luminosity of 0.66 pb(-1). Events with a low number of charged particles with p(T) > 0.2 GeV in the interval vertical bar eta vertical bar < 1 between the jets are observed in excess of calculations that assume only color-exchange. The fraction of events produced via color-singlet exchange, f(CSE), is measured as a function of p(T)(jet2), the pseudorapidity difference between the two leading jets, and the azimuthal angular separation between the two leading jets. The fraction f(CSE) has values of 0.4-1.0%. The results are compared with previous measurements and with predictions from perturbative quantum chromodynamics. In addition, the first study of jet-gap-jet events detected in association with an intact proton using a subsample of events with an integrated luminosity of 0.40 pb(-1) is presented. The intact protons are detected with the Roman pot detectors of the TOTEM experiment. The f(CSE) in this sample is 2.91 +/- 0.70(stat)(-1.01)(+1.08)(syst) times larger than that for inclusive dijet production in dijets with similar kinematics.
Basu J, Reis BS, Peri S, Zha JK, Hua X, Ge L, Ferchen K, Nicolas E, Czyzewicz P, Cai KQ, Tan YF, Bass JIF, Walhout AJM, Grimes HL, Grivennikov SI, Mucida D, Kappes DJ
Show All Authors
Essential role of a ThPOK autoregulatory loop in the maintenance of mature CD4(+) T cell identity and function (opens in new window)
NATURE IMMUNOLOGY 2021 AUG; 22(8):969-982
The transcription factor ThPOK (encoded by the Zbtb7b gene) controls homeostasis and differentiation of mature helper T cells, while opposing their differentiation to CD4(+) intraepithelial lymphocytes (IELs) in the intestinal mucosa. Thus CD4 IEL differentiation requires ThPOK transcriptional repression via reactivation of the ThPOK transcriptional silencer element (Sil(ThPOK)). In the present study, we describe a new autoregulatory loop whereby ThPOK binds to the Sil(ThPOK) to maintain its own long-term expression in CD4 T cells. Disruption of this loop in vivo prevents persistent ThPOK expression, leads to genome-wide changes in chromatin accessibility and derepresses the colonic regulatory T (T-reg) cell gene expression signature. This promotes selective differentiation of naive CD4 T cells into GITR(lo)PD-1(lo)CD25(lo) (Triple(lo)) T-reg cells and conversion to CD4(+) IELs in the gut, thereby providing dominant protection from colitis. Hence, the ThPOK autoregulatory loop represents a key mechanism to physiologically control ThPOK expression and T cell differentiation in the gut, with potential therapeutic relevance. The transcription factor ThPOK is critical for homeostasis and differentiation of mature helper T cells. Here, Kappes and colleagues describe a ThPOK-mediated positive autoregulatory loop that is crucial for tissue-specific T-reg cell differentiation, maintenance of intestinal T-reg cell integrity and conversion of these cells into CD4(+) intraepithelial lymphocytes.
Walloe S, Chakraborty M, Balsby TJS, Jarvis ED, Dabelsteen T, Pakkenberg B
Show All Authors
A Relationship between the Characteristics of the Oval Nucleus of the Mesopallium and Parrot Vocal Response to Playback (opens in new window)
BRAIN BEHAVIOR AND EVOLUTION 2021 AUG; 96(1):37-48
Correlations between differences in animal behavior and brain structures have been used to infer function of those structures. Brain region size has especially been suggested to be important for an animal's behavioral capability, controlled by specific brain regions. The oval nucleus of the mesopallium (MO) is part of the anterior forebrain vocal learning pathway in the parrot brain. Here, we compare brain volume and total number of neurons in MO of three parrot species (the peach-fronted conure, Eupsittula aurea, the peach-faced lovebird, Agapornis roseicollis, and the budgerigar, Melopsittacus undulatus), relating the total neuron numbers with the vocal response to playbacks of each species. We find that individuals with the highest number of neurons in MO had the shortest vocal latency. The peach-fronted conures showed the shortest vocal latency and largest number of MO neurons, the peach-faced lovebird had intermediary levels of both, and the budgerigar had the longest latency and least number of neurons. These findings indicate the MO nucleus as one candidate region that may be part of what controls the vocal capacity of parrots.
Halford B
Show All Authors
Proteomics path paver is using organic chemistry to glean information on immune system proteins (opens in new window)
CHEMICAL & ENGINEERING NEWS 2021 AUG 16; 99(30):48-49
Bosch B, De Jesus MA, Poulton NC, Zhang WZ, Engelhart CA, Zaveri A, Lavalette S, Ruecker N, Trujillo C, Wallach JB, Li SQ, Ehrt S, Chait BT, Schnappinger D, Rock JM
Show All Authors
Genome-wide gene expression tuning reveals diverse vulnerabilities of M. tuberculosis (opens in new window)
CELL 2021 AUG 19; 184(17):4579-4592.e24 Article e24
Antibacterial agents target the products of essential genes but rarely achieve complete target inhibition. Thus, the all-or-none definition of essentiality afforded by traditional genetic approaches fails to discern the most attractive bacterial targets: those whose incomplete inhibition results in major fitness costs. In contrast, gene "vulnerability'' is a continuous, quantifiable trait that relates the magnitude of gene inhibition to the effect on bacterial fitness. We developed a CRISPR interference-based functional genomicsmethod to systematically titrate gene expression in Mycobacterium tuberculosis (Mtb) and monitor fitness outcomes. We identified highly vulnerable genes in various processes, including novel targets unexplored for drug discovery. Equally important, we identified invulnerable essential genes, potentially explaining failed drug discovery efforts. Comparison of vulnerability between the reference and a hypervirulent Mtb isolate revealed incomplete conservation of vulnerability and that differential vulnerability can predict differential antibacterial susceptibility. Our results quantitatively redefine essential bacterial processes and identify high-value targets for drug development.
Kanzaki N, Yamashita T, Lee JS, Shih PY, Ragsdale EJ, Shinya R
Show All Authors
Tokorhabditis n. gen. (Rhabditida, Rhabditidae), a comparative nematode model for extremophilic living (opens in new window)
SCIENTIFIC REPORTS 2021 AUG 13; 11(1):? Article 16470
Life in extreme environments is typically studied as a physiological problem, although the existence of extremophilic animals suggests that developmental and behavioral traits might also be adaptive in such environments. Here, we describe a new species of nematode, Tokorhabditistufae, n. gen., n. sp., which was discovered from the alkaline, hypersaline, and arsenic-rich locale of Mono Lake, California. The new species, which offers a tractable model for studying animal-specific adaptations to extremophilic life, shows a combination of unusual reproductive and developmental traits. Like the recently described sister group Auanema, the species has a trioecious mating system comprising males, females, and self-fertilizing hermaphrodites. Our description of the new genus thus reveals that the origin of this uncommon reproductive mode is even more ancient than previously assumed, and it presents a new comparator for the study of mating-system transitions. However, unlike Auanema and almost all other known rhabditid nematodes, the new species is obligately live-bearing, with embryos that grow in utero, suggesting maternal provisioning during development. Finally, our isolation of two additional, molecularly distinct strains of the new genus-specifically from non-extreme locales-establishes a comparative system for the study of extremophilic traits in this model.
Blaze J, Navickas A, Phillips HL, Heissel S, Plaza-Jennings A, Miglani S, Asgharian H, Foo M, Katanski CD, Watkins CP, Pennington ZT, Javidfar B, Espeso-Gil S, Rostandy B, Alwaseem H, Hahn CG, Molina H, Cai DJ, Pan T, Yao WD, Goodarzi H, Haghighi F, Akbarian S
Show All Authors
Neuronal Nsun2 deficiency produces tRNA epitranscriptomic alterations and proteomic shifts impacting synaptic signaling and behavior (opens in new window)
NATURE COMMUNICATIONS 2021 AUG 13; 12(1):? Article 4913
The link between tRNA modifications, protein translation, and behavior is unclear. Here, the authors show that neuronal Nsun2 deficiency results in codon-specific epitranscriptomic changes of Gly-tRNAs and proteomic changes affecting synaptic signaling and behavior in mice. Epitranscriptomic mechanisms linking tRNA function and the brain proteome to cognition and complex behaviors are not well described. Here, we report bi-directional changes in depression-related behaviors after genetic disruption of neuronal tRNA cytosine methylation, including conditional ablation and transgene-derived overexpression of Nsun2 in the mouse prefrontal cortex (PFC). Neuronal Nsun2-deficiency was associated with a decrease in tRNA m(5)C levels, resulting in deficits in expression of 70% of tRNA(Gly) isodecoders. Altogether, 1488/5820 proteins changed upon neuronal Nsun2-deficiency, in conjunction with glycine codon-specific defects in translational efficiencies. Loss of Gly-rich proteins critical for glutamatergic neurotransmission was associated with impaired synaptic signaling at PFC pyramidal neurons and defective contextual fear memory. Changes in the neuronal translatome were also associated with a 146% increase in glycine biosynthesis. These findings highlight the methylation sensitivity of glycinergic tRNAs in the adult PFC. Furthermore, they link synaptic plasticity and complex behaviors to epitranscriptomic modifications of cognate tRNAs and the proteomic homeostasis associated with specific amino acids.
Hu JJ, Molinari E, Darmon S, Zhang L, Patrizio P, Barad DH, Gleicher N
Show All Authors
Valor predictivo de los patrones de granulacion del citoplasma durante Fecundacion in vitro en ovocitos en metafase II: Parte I, pacientes con mal pronostico (opens in new window)
FERTILITY AND STERILITY 2021 AUG; 116(2):431-443
Objective: To determine whether 4 cytoplasmic granulation patterns of human metaphase II oocytes have a predictive value for in vitro fertilization outcomes. Design: A retrospective cohort study. Setting: An academically affiliated private clinical infertility and research center. Patient(s): A total of 2,690 consecutive fresh autologous oocytes collected from women aged 41.2 + 5.0 years between 2017 and 2019. Intervention(s): Determination of granulation pattern in every oocyte during intracytoplasmic sperm injection as fine, central, dispersed, and newly introduced uneven granulations. Main Outcome Measure(s): Fertilization outcomes (2 pronuclei [2PN], <2PN, and >2PN rates), pregnancy, and live birth rates for different granulation patterns at different ages. Result(s): Fine granulation produced the highest 2PN rate, followed by central, uneven, and dispersed granulation (91.8%, 83.9%, 77.9%, and 54.8%, respectively). Differences in fertilization were surprisingly relatively independent of age and other variables. Overall, compared with fine granulation, dispersed granulation resulted in lower pregnancy rates (4.6% vs. 10.7%) and known-outcome analysis (1.3% vs. 5.6%) as well as lower live birth rates (3.0% vs. 8.9%) and known-outcome analysis (0.6% vs. 5.6%). The known-outcome analysis demonstrated that uneven granulation had lower live birth rates than fine granulation (2.3% vs. 5.6%). Unexpectedly, the ooplasm granulation patterns were largely disassociated from embryo morphologic grades. Conclusion(s): We, for the first time, demonstrated that 4 distinct cytoplasmic granulation patterns in metaphase II oocytes had, largely independent of age and other variables, a predictive value for fertilization, pregnancy, and live birth outcomes in in vitro fertilization cycles of poor-prognosis patients. These data suggest that upstream ooplasm granulation patterns deserve closer attention in terms of embryo selection.
Ou C, Li C, Zhang RS, Yang Q, Zong GH, Dai YW, Francis RL, Bournazos S, Ravetch JV, Wang LX
Show All Authors
One-Pot Conversion of Free Sialoglycans to Functionalized Glycan Oxazolines and Efficient Synthesis of Homogeneous Antibody-Drug Conjugates through Site-Specific Chemoenzymatic Glycan Remodeling (opens in new window)
BIOCONJUGATE CHEMISTRY 2021 AUG 18; 32(8):1888-1897
Antibody-drug conjugates (ADCs) are an important class of therapeutic agents that harness the highly specific antigen targeting property of antibodies to deliver toxic drugs for targeted cell killing. Site-specific conjugation methods are highly desirable for constructing homogeneous ADCs that possess a well-defined antibody-to-drug ratio, stability, ideal pharmacological profile, and optimal therapeutic index. We report here a facile synthesis of functionalized glycan oxazolines from free sialoglycans that are key donor substrates for enzymatic Fc glycan remodeling and the application of an efficient endoglycosidase mutant (Endo S2 D184M) for site-specific glycan transfer to construct homogeneous ADCs. We found that by a sequential use of two coupling reagents under optimized conditions, free sialoglycans could be efficiently converted to selectively functionalized glycan oxazolines carrying azide-, cyclopropene-, and norbornene-tags, respectively, in excellent yield and in a simple one-pot manner. We further demonstrated that the recently reported Endo-S2 D184 M mutant was highly efficient for Fc glycan remodeling with the selectively modified glycan oxazolines to introduce tags into an antibody, which required a significantly smaller amount of glycan oxazolines and a much shorter reaction time than that of the Endo-S D233Q:catalyzed reaction, thus minimizing the side reactions. Finally homogeneous ADCs were constructed with three different click reactions. The resulting ADCs showed excellent serum stability, and in vitro cytotoxicity assays indicated that all the three ADCs generated from the distinct click reactions possessed potent and comparable cytotoxicity for targeted cancer cell killing.