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Found 37769 matches. Displaying 3861-3870
Czarnowicki T, He HY, Wen HC, Hashim PW, Nia JK, Malik K, Estrada Y, Kimmel GW, Taliercio M, Krueger JG, Guttman-Yassky E
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Alopecia areata is characterized by expansion of circulating Th2/Tc2/Th22, within the skin-homing and systemic T-cell populations
ALLERGY 2018 MAR; 73(3):713-723
BackgroundCharacterizing blood profile of alopecia areata (AA) is important not only for treatment advancements, but also for possibly identifying peripheral biomarkers that will eliminate the need for scalp biopsies. We aimed to compare frequencies of skin homing (CLA(+)) vs systemic (CLA(-)) polar CD4(+) and CD8(+) and activated T-cell subsets in AA vs atopic dermatitis (AD) and control blood. MethodsFlow cytometry was used to measure IFN-, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4(+) and CD8(+) T cells. Inducible co-stimulator molecule (ICOS) and HLA-DR were used to define mid- and long-term T-cell activation. We compared peripheral blood from 32 moderate-to-severe AA adults with 43 moderate-to-severe AD patients and 30 age-matched controls. ResultsAA patients had increased CLA(+)/CLA(-) Th2 (P<.007), CLA(+) Tc2 (P=.04), and CLA(+) Th22 (P<.05) frequencies than controls. Except of CLA(-) Tc1 cells (P=.03), IFN- levels were mostly similar between AA, AD, and controls (P>.1). ICOS and HLA-DR activation were significantly higher in AA than controls (P<.05). T regulatory cells were significantly decreased in AA patients than controls (P<.01) and were correlated with activated CD8(+) T cells and with multiple cytokine subsets (P<.05). While Th2 and Tc2 clustered with disease severity, IFN- producing cells were linked with AA duration. ConclusionsAlopecia areata is accompanied by Th2/Tc2 activation in skin-homing and systemic subsets, correlating with disease severity, while IFN- is linked to disease chronicity. These data hint for a possible role of diverse T-cells subsets in disease pathogenesis and emphasize the systemic nature of AA supporting the need for systemic therapeutic strategies in severe patients.
Zhang HY, Freitas D, Kim HS, Fabijanic K, Li Z, Chen HY, Mark MT, Molina H, Martin AB, Bojmar L, Fang J, Rampersaud S, Hoshino A, Matei I, Kenific CM, Nakajima M, Mutvei AP, Sansone P, Buehring W, Wang HJ, Jimenez JP, Cohen-Gould L, Paknejad N, Brendel M, Manova-Todorova K, Magalhaes A, Ferreira JA, Osorio H, Silva AM, Massey A, Cubillos-Ruiz JR, Galletti G, Giannakakou P, Cuervo AM, Blenis J, Schwartz R, Brady MS, Peinado H, Bromberg J, Matsui H, Reis CA, Lyden D
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Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation
NATURE CELL BIOLOGY 2018 MAR; 20(3):332-343
The heterogeneity of exosomal populations has hindered our understanding of their biogenesis, molecular composition, biodistribution and functions. By employing asymmetric flow field-flow fractionation (AF4), we identified two exosome subpopulations (large exosome vesicles, Exo-L, 90-120 nm; small exosome vesicles, Exo-S, 60-80 nm) and discovered an abundant population of non-membranous nanoparticles termed 'exomeres' (similar to 35 nm). Exomere proteomic profiling revealed an enrichment in metabolic enzymes and hypoxia, microtubule and coagulation proteins as well as specific pathways, such as glycolysis and mTOR signalling. Exo-S and Exo-L contained proteins involved in endosomal function and secretion pathways, and mitotic spindle and IL-2/STAT5 signalling pathways, respectively. Exo-S, Exo-L and exomeres each had unique N-glycosylation, protein, lipid, DNA and RNA profiles and biophysical properties. These three nanoparticle subsets demonstrated diverse organ biodistribution patterns, suggesting distinct biological functions. This study demonstrates that AF4 can serve as an improved analytical tool for isolating extracellular vesicles and addressing the complexities of heterogeneous nanoparticle subpopulations.
Petersheim D, Massaad MJ, Lee S, Scarselli A, Cancrini C, Moriya K, Sasahara Y, Lankester AC, Dorsey M, Di Giovanni D, Bezrodnik L, Ohnishi H, Nishikomori R, Tanita K, Kanegane H, Morio T, Gelfand EW, Jain A, Secord E, Picard C, Casanova JL, Albert MH, Torgerson TR, Geha RS
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Mechanisms of genotype-phenotype correlation in autosomal dominant anhidrotic ectodermal dysplasia with immune deficiency
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 2018 MAR; 141(3):1060-1073.e3
Background: Autosomal dominant anhidrotic ectodermal dysplasia with immune deficiency (AD EDA-ID) is caused by heterozygous point mutations at or close to serine 32 and serine 36 or N-terminal truncations in I kappa B alpha that impair its phosphorylation and degradation and thus activation of the canonical nuclear factor kappa light chain enhancer of activated B cells (NF-kappa B) pathway. The outcome of hematopoietic stem cell transplantation is poor in patients with AD EDA-ID despite achievement of chimerism. Mice heterozygous for the serine 32I mutation in I kappa B alpha have impaired noncanonical NF-kappa B activity and defective lymphorganogenesis. Objective: We sought to establish genotype-phenotype correlation in patients with AD EDA-ID. Methods: A disease severity scoring system was devised. Stability of I kappa B alpha mutants was examined in transfected cells. Immunologic, biochemical, and gene expression analyses were performed to evaluate canonical and noncanonical NF-kappa B signaling in skin-derived fibroblasts. Results: Disease severity was greater in patients with IkBa point mutations than in those with truncation mutations. IkBa point mutants were expressed at significantly higher levels in transfectants compared with truncation mutants. Canonical NF-kappa B-dependent IL-6 secretion and upregulation of the NF-kappa B subunit 2/p100 and RELB proto-oncogene, NF-kappa B subunit (RelB) components of the noncanonical NF-kappa B pathway were diminished significantly more in patients with point mutations compared with those with truncations. Noncanonical NF-kappa B-driven generation of the transcriptionally active p100 cleavage product p52 and upregulation of CCL20, intercellular adhesion molecule 1 (ICAM1), and vascular cell adhesion molecule 1 (VCAM1), which are important for lymphorganogenesis, were diminished significantly more in LPS plus alpha-lymphotoxin beta receptor-stimulated fibroblasts from patients with point mutations compared with those with truncations. Conclusions: I kappa B alpha point mutants accumulate at higher levels compared with truncation mutants and are associated with more severe disease and greater impairment of canonical and noncanonical NF-kappa B activity in patients with AD EDA-ID.
Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, Brandstetter J, Brondolin E, Dragicevic M, Ero J, Flechl M, Friedl M, Fruhwirthl R, Ghete VM, Grossmann J, Hrubec J, Jeitlerl M, Konig A, Krammer N, Kratschmer I, Liko D, Madlener T, Mikulec I, Pree E, Rabady D, Rad N, Rohringer H, Schieckl J, Schoefbeck R, Spanring M, Spitzbart D, Waltenberger W, Wittmann J, Wulz CE, Zarucki M, Chekhovsky V, Mossolov V, Gonzalez JS, De Wolf EA, Di Croce D, Janssen X, Lauwers J, Van De Klundert M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Abu Zeid S, Blekman F, D'Hondt J, De Bruyn I, De Clercq J, Deroover K, Flouris G, Lontkovskyi D, Lowette S, Moortgat S, Moreels L, Python Q, Skovpen K, Tavernier S, Van Doninck W, Van Mulders P, Van Parijs I, Brun H, Clerbaux B, De Lentdecker G, Delannoy H, Fasanella G, Favart L, Goldouzian R, Grebenyuk A, Karapostoli G, Lenzi T, Luetic J, Maerschalk T, Marinov A, Randle-Conde A, Seva T, Vander Velde C, Vanlaer P, Vannerom D, Yonamine R, Zenoni F, Zhang F, Cimmino A, Cornelis T, Dobur D, Fagot A, Gul M, Khvastunov I, Poyraz D, Roskas C, Salva S, Tytgat M, Verbeke W, Zaganidis N, Bakhshiansohi H, Bondu O, Brochet S, Bruno G, Caputo C, Caudron A, De Visscher S, Delaere C, Delcourt M, Francois B, Giammanco A, Jafari A, Komm M, Krintiras G, Lemaitre V, Magitteri A, Mertens A, Musich M, Piotrzkowski K, Quertenmont L, Marono MV, Wertz S, Beliy N, Alda WL, Alves FL, Alves GA, Brito L, Martins MC, Hensel C, Moraes A, Pol ME, Teles PR, Das Chagas EBB, Carvalho W, Chinellato J, Custodio A, Da Costa EM, Da Silveira GG, Damiao DD, De Souza SF, Guativa LMH, Malbouisson H, De Almeida MM, Herrera CM, Mundim L, Nogima H, Santoro A, Sznajder A, Manganote EJT, De Araujo FTD, Pereira AV, Ahuja S, Bernardes CA, Tomei TRFP, Gregores EM, Mercadante PC, Novaes SF, Padula SS, Abad DR, Vargas JCR, Aleksandrov A, Hadjiiska R, Iaydjiev P, Misheva M, Rodozov M, Shopova M, Stoykova S, Sultanov G, Dimitrov A, Glushkov I, Litov L, Pavlov B, Petkov P, Fang W, Gao X, Ahmad M, Bian JG, Chen GM, Chen HS, Chen M, Chen Y, Jiang CH, Leggat D, Liao H, Liu Z, Romeo F, Shaheen SM, Spiezia A, Tao J, Wang C, Wang Z, Yazgan E, Zhang H, Zhang S, Zhao J, Ban Y, Chen G, Li Q, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Avila C, Cabrera A, Sierra LFC, Florez C, Hernandez CFG, Alvarez JDR, Courbon B, Godinovic N, Lelas D, Puljak I, Cipriano PMR, Sculac T, Antunovic Z, Kovac M, Brigljevic V, Ferencek D, Kadija K, Mesic B, Starodumov A, Susa T, Ather MW, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Finger M, Finger M, Jarrin EC, Assran Y, Mahmoud MA, Mahrous A, Dewanjee RK, Kadastik M, Perrini L, Raidal M, Tiko A, Veelken C, Eerola P, Pekkanen J, Voutilainen M, Harkonen J, Jarvinen T, Karimaki V, Kinnunen R, Lampen T, Lassila-Perini K, Lehti S, Linden T, Luukka P, Tuominen E, Tuominiemi J, Tuovinen E, Talvitie J, Tuuva T, Besancon M, Couderc F, Dejardin M, Denegri D, Faure JL, Ferri F, Ganjour S, Ghosh S, Givernaud A, Gras P, de Monchenault GH, Jarry P, Kucher I, Locci E, Machet M, Malcles J, Negro G, Rander J, Rosowsky A, Sahin MO, Titov M, Abdulsalam A, Antropov I, Baffioni S, Beaudette F, Busson P, Cadamuro L, Charlot C, de Cassagnac RG, Jo M, Lisniak S, Lobanov A, Blanco JM, Nguyen M, Ochando C, Ortona G, Paganini P, Pigard P, Regnard S, Salerno R, Sauvan JB, Sirois Y, Leiton AGS, Strebler T, Yilmaz Y, Zabi A, Zghiche A, Agram JL, Andrea J, Bloch D, Brom JM, Buttignol M, Chabert EC, Chanon N, Collard C, Conte E, Coubez X, Fontaineu JC, Gele D, Goerlach U, Jansova M, Le Bihan AC, Tonon N, Van Hove P, Gadrat S, Beauceron S, Bernet C, Boudoul G, Chierici R, Contardo D, Depasse P, El Mamouni H, Fay J, Finco L, Gascon S, Gouzevitch M, Grenier G, Ille B, Lagarde F, Laktineh IB, Lethuillier M, Mirabito L, Pequegnot AL, Perries S, Popov A, Sordini V, Vander Donckt M, Viret S, Khvedelidze A, Lomidze D, Autermann C, Beranek S, Feld L, Kiesel MK, Klein K, Lipinski M, Preuten M, Schomakers C, Schulz J, Verlage T, Zhukov V, Albert A, Dietz-Laursonn E, Duchardt D, Endres M, Erdmann M, Erdweg S, Esch T, Fischer R, Guth A, Hamer M, Hebbeker T, Heidemann C, Hoepfner K, Knutzen S, Merschmeyer M, Meyer A, Millet P, Mukherjee S, Olschewski M, Padeken K, Pook T, Radziej M, Reithler H, Rieger M, Scheuch F, Teyssier D, Thuer S, Flugge G, Kargoll B, Kress T, Kunsken A, Lingemann J, 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, Gizhko A, Luyando JMG, Grohsjean A, Gunnellini P, Guthoff M, Harb A, Hauk J, Hempel M, Jung H, Kalogeropoulos A, Kasemann M, Keaveney J, Kleinwort C, Korol I, Krucker D, Lange W, Lelek A, Lenz T, Leonard J, Lipka K, Lohmann W, Mankel R, Melzer-Pellmann IA, Meyer AB, Mittag G, Mnich J, Mussgiller A, Ntomari E, Pitzl D, Raspereza A, Roland B, Savitskyi M, Saxena P, Shevchenko R, Spannagel S, Stefaniuk N, Van Onsem GP, Walsh R, Wen Y, Wichmann K, Wissing C, Zenaiev O, Bein S, Blobel V, Vignali MC, Dreyer T, Garutti E, Gonzalez D, Haller J, Hinzmann A, Hoffmann M, Karavdina A, Klanner R, Kogler R, Kovalchuk N, Kurz S, Lapsien T, Marchesini I, Marconi D, Meyer M, Niedziela M, Nowatschin D, Pantaleo F, Peiffer T, Perieanu A, Scharf C, Schleper P, Schmidt A, Schumann S, Schwandt J, Sonneveld J, Stadie H, Steinbruck G, Stober FM, Stover M, Tholen H, Troendle D, Usai E, Vanelderen L, Vanhoefer A, Vormwald B, Akbiyik M, Barth C, Baur S, Butz E, Caspart R, Chwalek T, Colombo F, De Boer W, Dierlamm A, Freund B, Friese R, Giffels M, Gilbert A, Haitz D, Hartmann F, Heindl SM, Husemann U, Kassel F, Kudella S, Mildner H, Mozer MU, Mueller T, Plagge M, Quast G, Rabbertz K, Schroder M, Shvetsov I, Sieber G, Simonis HJ, Ulrich R, Wayand S, Weber M, Weiler T, Williamson S, Wohrmann C, Wolf R, Anagnostou G, Daskalakis G, Geralis T, Giakoumopoulou VA, Kyriakis A, Loukas D, Topsis-Giotis I, Karathanasis G, Kesisoglou S, Panagiotou A, Saoulidou N, Kousouris K, Evangelou I, Foudas C, Kokkas P, Mallios S, Manthos N, Papadopoulos I, Paradas E, Strologas J, Triantis FA, Csanad M, Filipovic N, Pasztor G, Veres GI, Bencze G, Hajdu C, Horvath D, Hunyadi A, Sikler F, Veszpremi V, Zsigmond AJ, 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, Bhowmik S, Mal P, Mandal K, Nayak A, Sahoo DK, Sahoo N, Swain SK, Bansal S, Beri SB, Bhatnagar V, Chawla R, Dhingra N, Kalsi AK, Kaur A, Kaur M, Kumar R, Kumari P, Mehta A, Singh JB, Walia G, Kumar A, Shah A, Bhardwaj A, Chauhan S, Choudhary BC, Garg RB, Keshri S, Kumar A, Malhotra S, Naimuddin M, Ranjan K, Sharma R, Bhardwaj R, Bhattacharya R, Bhattacharya S, Bhawandeep U, Dey S, Dutt S, Dutta S, Ghosh S, Majumdar N, Modak A, Mondal K, Mukhopadhyay S, Nandan S, Purohit A, Roy A, Roy D, Chowdhury SR, Sarkar S, Sharan M, 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, Bhattacharya S, Chatterjee S, Das P, Guchait M, Jain S, Kumar S, Maity M, Majumder G, Mazumdar K, Sarkar T, Wickramage N, Chauhan S, 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, Miniello G, My S, Nuzzo S, Pompili A, Pugliese G, Radogna R, Ranieri A, Selvaggi G, Sharma A, Silvestris L, Venditti R, Verwilligen P, Abbiendi G, Battilana C, Bonacorsi D, 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, 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, Fabbri F, Piccolo D, Primavera F, Calvelli V, Ferro F, Robutti E, Tosi S, Benaglia 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, De Oliveira ACA, Checchia P, Dall'Osso M, Manzano PD, Dorigo T, Dosselli U, Gasparini F, Gozzelino A, Lacaprara S, Lujan P, Margoni M, Meneguzzo AT, Pozzobon N, Ronchese P, Rossin R, Simonetto F, Ventura S, 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, Cecchia 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, 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, Martini L, Messineo A, Palla F, Rizzi A, Savoy-Navarro A, Spagnolo P, Tenchini R, Tonelli G, Venturi A, Verdini PC, 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, Marlotti C, Maselli S, Migliore E, Monaco V, Monteil E, Monteno M, Obertino MM, Pacher L, Pastrone N, Pelliccioni M, Angioni GLP, Ravera F, 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, Lee A, 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, Lee S, Lim J, Park SK, Roh Y, Almond J, Kim J, Kim JS, Lee H, Lee K, Nam K, Oh SB, Radburn-Smith BC, Seo SH, Yang UK, Yoo HD, Yu GB, Choi M, Kim H, Kim JH, Lee JSH, Park IC, Choi Y, Hwang C, Lee J, Yu I, Dudenas V, Juodagalvis A, Vaitkus J, Ahmed I, Ibrahim ZA, Ali MABM, Idris FM, Abdullah WATW, Yusli MN, Zolkapli Z, Reyes-Almanza R, Ramirez-Sanchez G, Duran-Osuna MC, Castilla-Valdez H, De La Cruz-Burelo E, Heredia-De La Cruz I, Rabadan-Trejo RI, Lopez-Fernandez R, Guisao JM, Sanchez-Hernandez A, Moreno SC, Barrera CO, Valencia FV, Pedraza I, Ibarguen HAS, Estrada CU, Pineda AM, Krofcheck D, Butler PH, Ahmad A, Ahmad M, Hassan Q, Hoorani HR, Qazi S, Saddique A, Shah MA, 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, Golutvin I, Karjavin V, Kashunin I, Korenkov V, Kozlov G, Laney A, Malakhov A, Matveev V, Mitsyn VV, Palichik V, Perelygin V, Shmatov S, Smirnov V, Trofimov V, Voytishin N, Yuldashev BS, Zarubin A, Zhiltsov 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, Stepennov A, Toms M, Vlasov E, Zhokin A, Aushev T, Bylinkin A, Chadeeva M, Parygin P, Philippov D, Polikarpov S, Popova E, Rusinov V, Andreev V, Azarkin M, Dremin I, Kirakosyan M, Terkulov A, Baskakov A, Belyaev A, Boos E, Bunichev V, Dubinin M, Dudko L, Gribushin A, Klyukhin V, Korneeva N, Lokhtin I, Miagkov I, Obraztsov S, Perfilov M, Savrin V, Volkov P, Blinov V, Skovpen Y, Shtol D, Azhgirey I, Bayshev I, Bitioukov S, Elumakhov D, Kachanov V, Kalinin A, Konstantinov D, Krychkine V, Petrov V, Ryutin R, Sobol A, Troshin S, Tyurin N, Uzunian A, Volkov A, Adzic P, Cirkovic P, Devetak D, Dordevic M, Milosevic J, Rekovic V, Maestre JA, Luna MB, Cerrada M, Colino N, De La Cruz B, Peris AD, Del Valle AE, Bedoya CF, Ramos JPF, Flix J, Fouz MC, Garcia-Abia P, Lopez O, Lopez SG, Hernandez JM, Josa MI, Yzquierdo APC, Pelayo JP, Olmeda AQ, Redondo I, Romero L, Soares MS, Fernandez AA, Albajar C, de Troconiz JF, Missiroli M, Moran D, Cuevas J, Erice C, Menendez JF, Caballero IG, Fernandez JRG, Cortezon EP, Cruz SS, Vischia P, Garcia JMV, Cabrillo IJ, Calderon A, Quero BC, Curras E, Campderros JD, Fernandez M, Garcia-Ferrero J, Gomez G, Virto AL, Marco J, Rivero CM, del Arbol PMR, Matorras F, Gomez JP, Rodrigo T, Ruiz-Jimeno A, Scodellaro L, Trevisani N, Vila I, Cortabitarte RV, Abbaneo D, Auffray E, Baillon P, Ball AH, Barney D, Bianco M, Bloch P, Bocci A, Botta C, Camporesi T, Castello R, Cepeda M, Cerminara G, Chapon E, Chen Y, d'Enterria D, Dabrowski A, Daponte V, David A, De Gruttola M, De Roeck A, Dobson M, Dorney B, du Pree T, Dunser M, Dupont N, Elliott-Peisert A, Everaerts P, Fallavollita F, Franzoni G, Fulcher J, Funk W, Gigi D, Gill K, Glege F, Gulhan D, Harris P, Hegeman J, Innocente V, Janot P, Karacheban O, Kieseler J, Kirschenmann H, 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, Orfanelli S, Orsini L, Pape L, Perez E, Peruzzi M, Petrilli A, Petrucciani G, Pfeiffer A, Pierini M, Racz A, Reis T, Rolandi G, Rovere M, Sakulin H, Schafer C, Schwick C, Seidel M, Selvaggi M, Sharma A, Silva P, Sphicas P, Stakia A, Steggemann J, Stoye M, Tosi M, Treille D, Triossi A, 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, Bachmair F, Bani L, Berger P, Bianchini L, Casal B, Dissertori G, Dittmar M, Donega M, 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, 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Teodorescu L, Turner M, 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 O, Zou D, Benelli G, Cutts D, Garabedian A, 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, Burns D, Sanchez MCD, Chertok M, Conway J, Conway R, Cox PT, Erbacher R, Flores C, Funk G, Gardner M, Ko W, Lander R, Mclean C, Mulhearn M, Pellett D, Pilot J, Shalhout S, Shi M, Smith J, Squires M, Stolp D, Tos K, Tripathi M, Wang Z, Bachtis M, Bravo C, Cousins R, Dasgupta A, Florent A, Hauser J, Ignatenko M, Mccoll N, Saltzberg D, Schnaible C, Valuev V, Bouvier E, Burt K, Clare R, Ellison J, Gary JW, Shirazi SMAG, Hanson G, Heilman J, Jandir P, Kennedy E, Lacroix F, Long OR, Negrete MO, Paneva MI, Shrinivas A, Si W, Wang L, Wei H, Wimpenny S, Yates BR, Branson JG, Cittolin S, Derdzinski M, Gerosa R, Hashemi B, Holzner A, Klein D, Kole G, Krutelyov V, Letts J, Macneill I, 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, George C, Golf F, Gouskos L, Gran J, Heller R, Incandela J, Mullin SD, Ovcharova A, Qu H, Richman J, Stuart D, Suarez I, Yoo J, Anderson D, Bendavid J, Bornheim A, Lawhorn JM, Newman HB, Nguyen T, Pena C, Spiropulu M, Vlimant JR, 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, Mulholland T, Stenson K, Wagner SR, Alexander J, Chaves J, Chu J, Dittmer S, Mcdermott K, Mirman N, Patterson JR, Rinkevicius A, Ryd A, Skinnari L, Soffi L, Tan SM, Tao Z, Thom J, Tucker J, Wittich P, Zientek M, Abdullin S, Albrow M, Apollinari G, Apresyan A, Apyan A, Banerjee S, 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, Geese Z, Gottschalk E, Gray L, Green D, Grunendahl S, Gutsche O, 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, Maruyama S, Mason D, McBride P, Merkel P, Mrenna S, Nahn S, O'Dell V, Pedro K, Prokofyev O, Rakness G, Ristori L, 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, Acosta D, Avery P, Bortignon P, Bourilkov D, Brinkerhoff A, Carnes A, Carver M, Curry D, Field RD, Furic IK, Konigsberg J, Korytov A, Kotov K, Ma P, Matchev K, Mei H, Mitselmakher G, Rank D, 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, Sharma V, 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, Royon C, Sanders S, Schmitz E, Takaki JDT, Wang Q, Ivanov A, Kaadze K, Maravin Y, Mohammadi A, Saini LK, Skhirtladze N, Toda S, Rebassoo F, Wright D, Anelli C, Baden A, Baron O, Belloni A, Calvert B, Eno SC, 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, Bi R, Brandt S, Busza W, Cali IA, D'Alfonso M, Demiragli Z, Ceballos GG, Goncharov M, Hsu D, Iiyama Y, Innocenti GM, Klute M, Kovalskyi D, Lai YS, 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, Tatar K, Velicanu D, Wang J, Wang TW, Wyslouch B, Benvenuti AC, Chatterjee RM, Evans A, Hansen P, Kalafut S, Kubota Y, Lesko Z, Mans J, Nourbakhsh S, Ruckstuhl N, Rusack R, Turkewitz J, Acosta JG, Oliveros S, Avdeeva E, Bloom K, Claes DR, Fangmeier C, Suarez RG, Kamalieddin R, Kravchenko I, Monroy J, Siado JE, Snow GR, Stieger B, Alyari M, Dolen J, Godshalk A, Harrington C, Iashvili I, Nguyen D, Parker A, Rappoccio S, Roozbahani B, Alverson G, Barberis E, Hortiangtham A, Massironi A, Morse DM, Nash D, Orimoto T, De Lima RT, Trocino D, Wood D, Bhattacharya S, Charaf O, Hahn KA, Mucia N, Odell N, Pollack B, Schmitt MH, Sung K, Trovato M, Velasco M, Dev N, Hildreth M, Anampa KH, Jessop C, Karmgard DJ, Kellams N, Lannon K, Loukas N, Marinelli N, Meng F, Mueller C, Musienko Y, Planer M, Reinsvold A, Ruchti R, Smith G, Taroni S, Wayne M, Wolf M, Woodard A, Alimena J, Antonelli L, Bylsma B, Durkin LS, Flowers S, Francis B, Hart A, Hill C, Ji W, Liu B, Luo W, Puigh D, Winer BL, Wulsin HW, Cooperstein S, Driga O, Elmer P, Hardenbrook J, Hebda P, Higginbotham S, Lange D, Luo J, Marlow D, Mei K, Ojalvo I, Olsen J, Palmer C, Piroue P, Stickland D, Tully C, Malik S, Norberg S, Barker A, Barnes VE, Das S, Folgueras S, Gutay L, Jha MK, Jones M, Jung AW, Khatiwada A, Miller DH, Neumeister N, Peng CC, Schulte JF, Sun J, Wang F, Xie W, Cheng T, Parashar N, Stupak J, Adair A, Akgun B, Chen Z, Ecklund KM, Geurts FJM, Guilbaud M, Li W, Michlin B, Northup M, Padley BP, Roberts J, Rorie J, Tu Z, Zabel J, 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, Foerster M, 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, Lee SW, Libeiro T, Peltola T, Undleeb S, Volobouev I, Wang Z, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Melo A, Ni H, 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, Wang Y, Wolfe E, Xia F, Harr R, Karchin PE, Sturdy J, Zaleski S, Brodski M, Buchanan J, Caillol C, Dasu S, Dodd L, Duric S, Comber B, Grothe M, Herndon M, Herve A, Hussain U, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Pierro GA, Polese G, Ruggles T, Savin A, Smith N, Smith WH, Taylor D, Woods N
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Measurement of the inclusive t(t)over-bar cross section in pp collisions root s=5.02 TeV using final states with at least one charged lepton
JOURNAL OF HIGH ENERGY PHYSICS 2018 MAR 20; ?(3):? Article 115
The top quark pair production cross section (ad) is measured for the first time in pp collisions at a center-of-mass energy of 5.02 TeV. The data were collected by the CMS experiment at the LHC and correspond to an integrated luminosity of 27.4 pb(-1). The measurement is performed by analyzing events with at least one charged lepton. The measured cross section is sigma(tt) = 69.5 +/- 6.1 (stat) +/- 5.6 (syst) +/- 1.6 (lumi) pb, with a total relative uncertainty of 12%. The result is in agreement with the expectation from the standard model. The impact of the presented measurement on the determination of the gluon distribution function is investigated.
Our body's epithelia are barriers that interface with the terrestrial environment and routinely experience inflammation. Although a vast majority of these inflammatory reactions resolve, they imprint the tissue with a memory. Cells of the immune system are traditionally thought to be the bearers of this memory, allowing them to react faster to subsequent inflammatory pressures (1, 2). Yet, barrier tissues are composites of epithelial, mesenchymal, nervous, vascular, and immunological networks working in unison to sustain optimal function in health and disease. The question of whether tissue-resident cells, distinct from the immune system, are entrained in response to a perturbation remains to be addressed.
Picard M, McEwen BS
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Psychological Stress and Mitochondria: A Systematic Review
PSYCHOSOMATIC MEDICINE 2018 FEB-MAR; 80(2):141-153
Objective Mitochondria are multifunctional life-sustaining organelles that represent a potential intersection point between psychosocial experiences and biological stress responses. This article provides a systematic review of the effects of psychological stress on mitochondrial structure and function. Methods A systematic review of the literature investigating the effects of psychological stress on mitochondrial function was conducted. The review focused on experimentally controlled studies allowing us to draw causal inference about the effect of induced psychological stress on mitochondria. Results A total of 23 studies met the inclusion criteria. All studies involved male laboratory animals, and most demonstrated that acute and chronic stressors influenced specific facets of mitochondrial function, particularly within the brain. Nineteen studies showed significant adverse effects of psychological stress on mitochondria and four found increases in function or size after stress. In humans, only six observational studies were available, none with experimental designs, and most only measured biological markers that do not directly reflect mitochondrial function, such as mitochondrial DNA copy number. Conclusons Overall, evidence supports the notion that acute and chronic stressors influence various aspects of mitochondrial biology, and that chronic stress exposure can lead to molecular and functional recalibrations among mitochondria. Limitations of current animal and human studies are discussed. Maladaptive mitochondrial changes that characterize this subcellular state of stress are termed mitochondrial allostatic load. Prospective studies with sensitive measures of specific mitochondrial outcomes will be needed to establish the link between psychosocial stressors, emotional states, the resulting neuroendocrine and immune processes, and mitochondrial energetics relevant to mind-body research in humans.
Chowell D, Morris LGT, Grigg CM, Weber JK, Samstein RM, Makarov V, Kuo FS, Kendall SM, Requena D, Riaz N, Greenbaum B, Carroll J, Garon E, Hyman DM, Zehir A, Solit D, Berger M, Zhou RH, Rizvi NA, Chan TA
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Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy
SCIENCE 2018 FEB 2; 359(6375):582-587
CD8(+) T cell-dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti-programmed cell death protein 1 or anti-cytotoxic T lymphocyte-associated protein 4 is currently unknown. We determined the HLA-I genotype of 1535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci ("A," "B," and "C") improved overall survival after ICB compared with patients who were homozygous for at least one HLA locus. In two independent melanoma cohorts, patients with the HLA-B44 supertype had extended survival, whereas the HLA-B62 supertype (including HLA-B*15:01) or somatic loss of heterozygosity at HLA-I was associated with poor outcome. Molecular dynamics simulations of HLA-B*15:01 revealed different elements that may impair CD8(+) T cell recognition of neoantigens. Our results have important implications for predicting response to ICB and for the design of neoantigen-based therapeutic vaccines.
Azimzadeh JB, Fabella BA, Kastan NR, Hudspeth AJ
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Thermal Excitation of the Mechanotransduction Apparatus of Hair Cells
NEURON 2018 FEB 7; 97(3):586-595.e4
Although a hair bundle is normally deflected by mechanical stimuli, we found that irradiation of a hair cell from the bullfrog's sacculus with ultraviolet light causes rapid motion of the hair bundle toward its tall edge. This movement is associated with opening of mechanotransduction channels and disappears when tip links are disrupted. We localized the absorptive element responsible for the motion to the region directly below the hair bundle and measured an action spectrum similar to the absorption spectra of mitochondrial constituents. Temperature measurements revealed heating around the site of absorption; direct heating of the hair bundle confirmed that the response to light is mediated through heat. Although mechanical offsets of the hair bundle revealed that heat softens gating springs, it also acts directly to open transduction channels. This study identifies an unconventional method of hair-cell stimulation and clarifies the previously unexplained sensitivity of auditory organs to thermal stimulation.
O'Shaughnessy MJ, Murray KS, La Rosa SP, Budhu S, Merghoub T, Somma A, Monette S, Kim K, Corradi RB, Scherz A, Coleman JA
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Systemic Antitumor Immunity by PD-1/PD-L1 Inhibition Is Potentiated by Vascular-Targeted Photodynamic Therapy of Primary Tumors
CLINICAL CANCER RESEARCH 2018 FEB 1; 24(3):592-599
Purpose: PD-1/PD-L1 pathway inhibition is effective against advanced renal cell carcinoma, although results are variable and may depend on host factors, including the tumor microenvironment. Vascular-targeted photodynamic (VTP) therapy with the photosensitizer WST11 induces a defined local immune response, and we sought to determine whether this could potentiate the local and systemic antitumor response to PD-1 pathway inhibition. Experimental Design: Using an orthotopic Renca murine model of renal cell carcinoma that develops lung metastases, we treated primary renal tumors with either VTP alone, PD-1/PD-L1 antagonistic antibodies alone, or a combination of VTP and antibodies and then examined treatment responses, including immune infiltration in primary and metastatic sites. Modulation of PD-L1 expression by VTP in human xenograft tumors was also assessed. Results: Treatment of renal tumors with VTP in combination with systemic PD-1/PD-L1 pathway inhibition, but neither treatment alone, resulted in regression of primary tumors, prevented growth of lung metastases, and prolonged survival in a preclinical mouse model. Analysis of tumor-infiltrating lymphocytes revealed that treatment effect was associated with increased CD8thorn: regulatory T cell (Treg) and CD4(+)FoxP3-: Treg ratios in primary renal tumors and increased T-cell infiltration in sites of lung metastasis. Furthermore, PD-L1 expression is induced following VTP treatment of human renal cell carcinoma xenografts. Conclusions: Our results demonstrate a role for local immune modulation with VTP in combination with PD-1/PD-L1 pathway inhibition for generation of potent local and systemic antitumor responses. This combined modality strategy may be an effective therapy in cancers resistant to PD-1/PD-L1 pathway inhibition alone. (C) 2017 AACR.
Marodi L
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Nobel Prize for the discoveries of genetic mechanisms controlling the circadian rhythm
ORVOSI HETILAP 2018 FEB; 159(6):239-239