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Found 37173 matches. Displaying 4711-4720
Rahi SJ, Pecani K, Ondracka A, Oikonomou C, Cross FR
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The CDK-APC/C Oscillator Predominantly Entrains Periodic Cell-Cycle Transcription
CELL 2016 APR 7; 165(2):475-487
Throughout cell-cycle progression, the expression of multiple transcripts oscillate, and whether these are under the centralized control of the CDK-APC/C proteins or can be driven by a de-centralized transcription factor (TF) cascade is a fundamental question for understanding cell-cycle regulation. In budding yeast, we find that the transcription of nearly all genes, as assessed by RNA-seq or fluorescence microscopy in single cells, is dictated by CDK-APC/C. Three exceptional genes are transcribed in a pulsatile pattern in a variety of CDK-APC/C arrests. Pursuing one of these transcripts, the SIC1 inhibitor of B-type cyclins, we use a combination of mathematical modeling and experimentation to provide evidence that, counter-intuitively, Sic1 provides a failsafe mechanism promoting nuclear division when levels of mitotic cyclins are low.
Krueger J, Clark JD, Suarez-Farinas M, Fuentes-Duculan J, Cueto I, Wang CQ, Tan HM, Wolk R, Rottinghaus ST, Whitley MZ, Valdez H, von Schack D, O'Neil SP, Reddy PS, Tatulych S
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Tofacitinib attenuates pathologic immune pathways in patients with psoriasis: A randomized phase 2 study
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 2016 APR; 137(4):1079-1090
Background: Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. Objective: We sought to elucidate the molecular mechanisms underlying the clinical efficacy of tofacitinib in patients with psoriasis. Methods: Twelve patients with plaque psoriasis were randomized (3: 1) to receive 10 mg of tofacitinib or placebo twice daily for 12 weeks. Biopsy specimens were taken from nonlesional (baseline) and lesional (baseline, days 1 and 3, and weeks 1, 2, 4, and 12) skin. Biopsy specimens were examined for psoriatic epidermal features (thickness, Ki67(+) keratinocytes and keratin 16 [KRT16] mRNA expression, and phosphorylated signal transducer and activator of transcription [pSTAT](+) nuclei) and T-cell and dendritic cell (DC) subsets by using immunohistochemistry, and mRNA transcripts were quantified by using a microarray. Results: In lesional skin keratinocyte pSTAT1 and pSTAT3 staining was increased at baseline but reduced after 1 day of tofacitinib (baseline, median of 1290 pSTAT1(+) cells/mu m(2); day 1, median of 332 pSTAT1(+) cells/mu m(2); and nonlesional, median of 155 pSTAT1(+) cells/mu m(2)). Epidermal thickness and KRT16 mRNA expression were significantly and progressively reduced after days 1 and 3 of tofacitinib administration, respectively (eg, KRT16 decreased 2.74-fold, day 3 vs baseline, P = .016). Decreases in DC and T-cell numbers were observed after weeks 1 and 2, respectively. At week 4, significant decreases in IL-23/T(H)17 pathways were observed that persisted through week 12. Improvements in clinical and histologic features were strongly associated with changes in expression of psoriasis-related genes and reduction in IL-17 gene expression. Conclusions: Tofacitinib has a multitiered response in patients with psoriasis: (1) rapid attenuation of keratinocyte Janus kinase/STAT signaling; (2) removal of keratinocyte-induced cytokine signaling, leading to reductions in pathologic DC and T-cell numbers to nonlesional levels; and (3) inhibition of the IL-23/T(H)17 pathway.
Yapici N, Cohn R, Schusterreiter C, Ruta V, Vosshall LB
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A Taste Circuit that Regulates Ingestion by Integrating Food and Hunger Signals
CELL 2016 APR 21; 165(3):715-729
Ingestion is a highly regulated behavior that integrates taste and hunger cues to balance food intake with metabolic needs. To study the dynamics of ingestion in the vinegar fly Drosophila melanogaster, we developed Expresso, an automated feeding assay that measures individual meal-bouts with high temporal resolution at nanoliter scale. Flies showed discrete, temporally precise ingestion that was regulated by hunger state and sucrose concentration. We identify 12 cholinergic local interneurons (IN1, for "ingestion neurons'') necessary for this behavior. Sucrose ingestion caused a rapid and persistent increase in IN1 interneuron activity in fasted flies that decreased proportionally in response to subsequent feeding bouts. Sucrose responses of IN1 interneurons in fed flies were significantly smaller and lacked persistent activity. We propose that IN1 neurons monitor ingestion by connecting sugar-sensitive taste neurons in the pharynx to neural circuits that control the drive to ingest. Similar mechanisms for monitoring and regulating ingestion may exist in vertebrates.
Czarnowicki T, Malajian D, Khattri S, da Rosa JC, Dutt R, Finney R, Dhingra N, Peng XY, Xu H, Estrada YD, Zheng XZ, Gilleaudeau P, Sullivan-Whalen M, Suarez-Farinas M, Shemer A, Krueger JG, Guttman-Yassky E
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Petrolatum: Barrier repair and antimicrobial responses underlying this "inert" moisturizer
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 2016 APR; 137(4):1091-1102
Background: Petrolatum is a common moisturizer often used in the prevention of skin infections after ambulatory surgeries and as a maintenance therapy of atopic dermatitis (AD). However, the molecular responses induced by petrolatum in the skin have never been assessed. Objective: We sought to define the cutaneous molecular and structural effects induced by petrolatum. Methods: Thirty-six healthy subjects and 13 patients with moderate AD (mean SCORAD score, 39) were studied by using RT-PCR, gene arrays, immunohistochemistry, and immunofluorescence performed on control skin, petrolatum-occluded skin, and skin occluded with a Finn chamber only. Results: Significant upregulations of antimicrobial peptides (S100A8/fold change [FCH], 13.04; S100A9/FCH, 11.28; CCL20/FCH, 8.36; PI3 [elafin]/FCH, 15.40; lipocalin 2/FCH, 6.94, human beta-defensin 2 [DEFB4A]/FCH, 4.96; P < .001 for all) and innate immune genes (IL6, IL8, and IL1B; P < .01) were observed in petrolatum-occluded skin compared with expression in both control and occluded-only skin. Application of petrolatum also induced expression of key barrier differentiation markers (filaggrin and loricrin), increased stratum corneum thickness, and significantly reduced T-cell infiltrates in the setting of "normal-appearing" or nonlesional AD skin, which is known to harbor barrier and immune defects. Conclusions: Petrolatum robustly modulates antimicrobials and epidermal differentiation barrier measures. These data shed light on the beneficial molecular responses of petrolatum in barrier-defective states, such as AD and postoperative wound care.
Lee EM, Alsagheir A, Wu XF, Hammack C, McLauchlan J, Watanabe N, Wakita T, Kneteman NM, Douglas DN, Tang HL
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Hepatitis C Virus-Induced Degradation of Cell Death-Inducing DFFA-Like Effector B Leads to Hepatic Lipid Dysregulation
JOURNAL OF VIROLOGY 2016 APR; 90(8):4174-4185
Individuals chronically infected with hepatitis C virus (HCV) commonly exhibit hepatic intracellular lipid accumulation, termed steatosis. HCV infection perturbs host lipid metabolism through both cellular and virus-induced mechanisms, with the viral core protein playing an important role in steatosis development. We have recently identified a liver protein, the cell death-inducing DFFA-like effector B (CIDEB), as an HCV entry host dependence factor that is downregulated by HCV infection in a cell culture model. In this study, we investigated the biological significance and molecular mechanism of this downregulation. HCV infection in a mouse model downregulated CIDEB in the liver tissue, and knockout of the CIDEB gene in a hepatoma cell line results in multiple aspects of lipid dysregulation that can contribute to hepatic steatosis, including reduced triglyceride secretion, lower lipidation of very-low-density lipoproteins, and increased lipid droplet (LD) stability. The potential link between CIDEB downregulation and steatosis is further supported by the requirement of the HCV core and its LD localization for CIDEB downregulation, which utilize a proteolytic cleavage event that is independent of the cellular proteasomal degradation of CIDEB. IMPORTANCE Our data demonstrate that HCV infection of human hepatocytes in vitro and in vivo results in CIDEB downregulation via a proteolytic cleavage event. Reduction of CIDEB protein levels by HCV or gene editing, in turn, leads to multiple aspects of lipid dysregulation, including LD stabilization. Consequently, CIDEB downregulation may contribute to HCV-induced hepatic steatosis.
de Carvalho MHC, Sun HX, Bowler C, Chua NH
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Noncoding and coding transcriptome responses of a marine diatom to phosphate fluctuations
NEW PHYTOLOGIST 2016 APR; 210(2):497-510
Phosphorus (P) is an essential element to all living cells, yet fluctuations in P concentrations are recurrent in the marine environment. Diatoms are amongst the most successful phytoplankton groups, adapting to and surviving periods of suboptimal conditions and resuming growth as soon as nutrient concentrations permit. A knowledge of the molecular underpinnings of diatom ecological success is, however, still very incomplete. By strand-specific RNA sequencing, we analyzed the global transcriptome changes of the diatom Phaeodactylum tricornutum in response to P fluctuations over a course of 8d, defining five distinct physiological states. This study reports previously unidentified genes highly responsive to P stress in P.tricornutum. Our data also uncover the complexity of the P.tricornutum P-responsive sensory and signaling system that combines bacterial two-component systems with more complex pathways reminiscent of metazoans. Finally, we identify a multitude of novel long intergenic nonprotein coding RNAs (lincRNAs) specifically responsive to P depletion, suggesting putative regulatory roles in the regulation of P homeostasis. Our work provides additional molecular insights into the resilience of diatoms and their ecological success, and opens up novel routes to address and explore the function and regulatory roles of P.tricornutum lincRNAs in the context of nutrient stress.
Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, Ero J, Friedl M, Fruhwirth R, Ghete VM, Hartl C, Hormann N, Hrubec J, Jeitler M, Kiesenhofer W, Knunz V, Krammer M, Kratschmer I, Liko D, Mikulec I, Rabady D, Rahbaran B, Rohringer H, Schofbeck R, Strauss J, Treberer-Treberspurg W, Waltenberger W, Wulz CE, Mossolov V, Shumeiko N, Gonzalez JS, Alderweireldt S, Bansal M, Bansal S, Cornelis T, De Wolf EA, Janssen X, Knutsson A, Lauwers J, Luyckx S, Ochesanu S, Rougny R, Van De Klundert M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Van Spilbeeck A, Van Remortel N, Van Spilbeeck A, Blekman F, Blyweert S, D'Hondt J, Daci N, Heracleous N, Keaveney J, Lowette S, Maes M, Olbrechts A, Python Q, Strom D, Tavernier S, Van Doninck W, Van Mulders P, Van Onsem GP, Villella I, Caillol C, Clerbaux B, De Lentdecker G, Dobur D, Favart L, Gay APR, Grebenyuk A, Leonard A, Mohammadi A, Pernie L, Reis T, Seva T, Thomas L, Velde CV, Vanlaer P, Wang J, Zenoni F, Adler V, Beernaert K, Benucci L, Cimmino A, Costantini S, Crucy S, Dildick S, Fagot A, Garcia G, Mccartin J, Rios AAO, Ryckbosch D, Diblen SS, Sigamani M, Strobbe N, Thyssen F, Tytgat M, Yazgan E, Zaganidis N, Basegmez S, Beluffi C, Bruno G, Castello R, Caudron A, Ceard L, Da Silveira GG, Delaere C, du Pree T, Favart D, Forthomme L, Giammanco A, Hollar J, Jafari A, Jez P, Komm M, Lemaitre V, Nuttens C, Pagano D, Perrini L, Pin A, Piotrzkowski K, Popov A, Quertenmont L, Selvaggi M, Marono MV, Garcia JMV, Beliy N, Caebergs T, Daubie E, Hammad GH, Alda WL, Alves GA, Brito L, Martins MC, Martins TD, Herrera CM, Pol ME, Carvalho W, Chinellato J, Custodio A, Da Costa EM, Damiao DD, Martins CD, De Souza SF, Malbouisson H, Figueiredo DM, Mundim L, Nogima H, Da Silva WLP, Santaolalla J, Santoro A, Sznajder A, Manganote EJT, Pereira AV, Bernardes CA, Dogra S, Tomei TRFP, Gregores EM, Mercadante PG, Novaes SF, Padula SS, Aleksandrov A, Genchev V, Iaydjiev P, Marinov A, Piperov S, Rodozov M, Sultanov G, Vutova M, Dimitrov A, Glushkov I, Hadjiiska R, Litov L, Pavlov B, Petkov P, Bian JG, Chen GM, Chen HS, Chen M, Cheng T, Du R, Jiang CH, Plestina R, Romeo F, Tao J, Wang Z, Asawatangtrakuldee C, Ban Y, Li Q, Liu S, Mao Y, Qian SJ, Wang D, Zou W, Avila C, Sierra LFC, Florez C, Gomez JP, Moreno BG, Sanabria JC, Godinovic N, Lelas D, Polic D, Puljak I, Antunovic Z, Kovac M, Brigljevic V, Kadija K, Luetic J, Mekterovic D, Sudic L, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Bodlak M, Finger M, Finger M, Assran Y, Elgammal S, Mahmoud MA, Radi A, Kadastik M, Murumaa M, Raidal M, Tiko A, Eerola P, Fedi G, Voutilainen M, Harkonen J, Karimaki V, Kinnunen R, Kortelainen MJ, Lampen T, Lassila-Perini K, Lehti S, Linden T, Luukka P, Maenpaa T, Peltola T, Tuominen E, Tuominiemi J, Tuovinen E, Wendland L, Talvitie J, Tuuva T, Besancon M, Couderc F, Dejardin M, Denegri D, Fabbro B, Faure JL, Favaro C, Ferri F, Ganjour S, Givernaud A, Gras P, de Monchenault GH, Jarry P, Locci E, Malcles J, Neveu J, Rander J, Rosowsky A, Titov M, Baffioni S, Beaudette F, Busson P, Charlot C, Dahms T, Dalchenko M, Dobrzynski L, Filipovic N, Florent A, de Cassagnac RG, Mastrolorenzo L, Mine P, Mironov C, Naranjo IN, Nguyen M, Ochando C, Paganini P, Regnard S, Salerno R, Sauvan JB, Sirois Y, Veelken C, Yilmaz Y, Zabi A, Agram JL, Andrea J, Aubin A, Bloch D, Brom JM, Chabert EC, Collard C, Conte E, Fontaine JC, Gele D, Goerlach U, Goetzmann C, Le Bihan AC, Van Hove P, Gadrat S, Beauceron S, Beaupere N, Boudoul G, Bouvier E, Brochet S, Montoya CAC, Chasserat J, Chierici R, Contardo D, Depasse P, El Mamouni H, Fan J, Fay J, Gascon S, Gouzevitch M, Ille B, Kurca T, Lethuillier M, Mirabito L, Perries S, Alvarez JDR, Sabes D, Sgandurra L, Sordini V, Donckt MV, Verdier P, Viret S, Xiao H, Rurua L, Autermann C, Beranek S, Bontenackels M, Edelhoff M, Feld L, Heister A, Hindrichs O, Klein K, Ostapchuk A, Raupach F, Sammet J, Schael S, Weber H, Wittmer B, Zhukov V, Ata M, Brodski M, Dietz-Laursonn E, Duchardt D, Erdmann M, Fischer R, Guth A, Hebbeker T, Heidemann C, Hoepfner K, Klingebiel D, Knutzen S, Kreuzer P, Merschmeyer M, Meyer A, Millet P, Olschewski M, Padeken K, Papacz P, Reithler H, Schmitz SA, Sonnenschein L, Teyssier D, Thuer S, Weber M, Cherepanov V, Erdogan Y, Flugge G, Geenen H, Geisler M, Ahmad WH, Hoehle F, Kargoll B, Kress T, Kuessel Y, Kuunsken A, Lingemann J, Nowack A, Nugent IM, Perchalla L, Pooth O, Stahl A, Asin I, Bartosik N, Behr J, Behrenhoff W, Behrens U, Bell AJ, Bergholz M, Bethani A, Borras K, Burgmeier A, Cakir A, Calligaris L, Campbell A, Choudhury S, Costanza F, Pardos CD, Dolinska G, Dooling S, Dorland T, Eckerlin G, Eckstein D, Eichhorn T, Flucke G, Garcia JG, Geiser A, Gunnellini P, Hauk J, Hempel M, Horton D, Jung H, Kalogeropoulos A, Kasemann M, Katsas P, Kieseler J, Kleinwort C, Korol I, Krucker D, Lange W, Leonard J, Lipka K, Lobanov A, Lohmann W, Lutz B, Mankel R, Marfin I, Melzer-Pellmann IA, Meyer AB, Mittag G, Mnich J, Mussgiller A, Naumann-Emme S, Nayak A, Novgorodova O, Ntomari E, Perrey H, Pitzl D, Placakyte R, Raspereza A, Cipriano PMR, Roland B, Ron E, Sahin MO, Salfeld-Nebgen J, Saxena P, Schmidt R, Schoerner-Sadenius T, Schroder M, Seitz C, Spannagel S, Vargas Trevino ADR, Walsh R, Wissing C, Martin MA, Blobel V, Vignali MC, Draeger AR, Erfle J, Garutti E, Goebel K, Gorner M, Haller J, Hoffmann M, Hooing RS, Kirschenmann H, Klanner R, Kogler R, Lange J, Lapsien T, Lenz T, Marchesini I, Ott J, Peiffer T, Perieanu A, Pietsch N, Poehlsen J, Poehlsen T, Rathjens D, Sander C, Schettler H, Schleper P, Schlieckau E, Schmidt A, Seidel M, Sola V, Stadie H, Steinbruck G, Troendle D, Usai E, Vanelderen L, Vanhoefer A, Barth C, Baus C, Berger J, Boser C, Butz E, Chwalek T, De Boer W, Descroix A, Dierlamm A, Frensch F, Giffels M, Gilbert A, Hartmann F, Hauth T, Husemann U, Katkov I, Kornmayer A, Kuznetsova E, Pardo PL, Mozer MU, Muller T, Nurnberg A, Quast G, Rabbertz K, Rocker S, Simonis HJ, Stober FM, Ulrich R, Wagner-Kuhr J, Wayand S, Weiler T, Wolf R, Anagnostou G, Daskalakis G, Geralis T, Giakoumopoulou VA, Kyriakis A, Loukas D, Markou A, Markou C, Psallidas A, Topsis-Giotis I, Agapitos A, Kesisoglou S, Panagiotou A, Saoulidou N, Stiliaris E, Aslanoglou X, Evangelou I, Flouris G, Foudas C, Kokkas P, Manthos N, Papadopoulos I, Paradas E, Strologas J, Bencze G, Hajdu C, Hidas P, Horvath D, Sikler F, Veszpremi V, Vesztergombi G, Zsigmond AJ, Beni N, Czellar S, Karancsi J, Molnar J, Palinkas J, Szillasi Z, Makovec A, Raics P, Trocsanyi ZL, Ujvari B, Swain SK, Beri SB, Bhatnagar V, Gupta R, Bhawandeep U, Kalsi AK, Kaur M, Kumar R, Mittal M, Nishu N, Singh JB, Kumar A, Kumar A, Ahuja S, Bhardwaj A, Choudhary BC, Kumar A, Malhotra S, Naimuddin M, Ranjan K, Sharma V, Banerjee S, Bhattacharya S, Chatterjee K, Dutta S, Gomber B, Jain S, Jain S, Khurana R, Modak A, Mukherjee S, Roy D, Sarkar S, Sharan M, Abdulsalam A, Dutta D, Kailas S, Kumar V, Mohanty AK, Pant LM, Shukla P, Topkar A, Aziz T, Banerjee S, Bhowmik S, Chatterjee RM, Dewanjee RK, Dugad S, Ganguly S, Ghosh S, Guchait M, Gurtu A, Kole G, Kumar S, Maity M, Majumder G, Mazumdar K, Mohanty GB, Parida B, Sudhakar K, Wickramage N, Bakhshiansohi H, Behnamian H, Etesami SM, Fahim A, Goldouzian R, Khakzad M, Najafabadi MM, Naseri M, Mehdiabadi SP, Hosseinabadi FR, Safarzadeh B, Zeinali M, Felcini M, Grunewald M, Abbrescia M, Calabria C, Chhibra SS, Colaleo A, Creanza D, De Filippis N, De Palmaa M, Fiore L, Iaselli G, Maggi G, Maggi M, My S, Nuzzo S, Pompili A, Pugliese G, Radogna R, Selvaggi G, Sharma A, Silvestris L, Venditti R, Abbiendi G, Benvenuti AC, Bonacorsi D, Braibant-Giacomelli S, Brigliadori L, Campanini R, Capiluppi P, Castro A, Cavallo FR, Codispoti G, Cuffiani M, Dallavalle GM, Fabbri F, Fanfani A, Fasanella D, Giacomelli P, Grandi C, Guiducci L, Marcellini S, Masetti G, Montanari A, Navarria FL, Perrotta A, Primavera F, Rossi AM, Rovelli T, Siroli GP, Tosi N, Travaglini R, Albergo S, Cappello G, Chiorboli M, Costa S, Giordano F, Potenza R, Tricomi A, Tuve C, Barbagli G, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Gallo E, Gonzi S, Gori V, Lenzi P, Meschini M, Paoletti S, Sguazzoni G, Tropiano A, Benussi L, Bianco S, Fabbri F, Piccolo D, Ferretti R, Ferro F, Lo Vetere M, Robutti E, Tosi S, Dinardo ME, Fiorendi S, Gennai S, Gerosa R, Ghezzi A, Govoni P, Lucchini MT, Malvezzi S, Manzoni RA, Martelli A, Marzocchi B, Menasce D, Moroni L, Paganoni M, Pedrini D, Ragazzi S, Redaelli N, de Fatis TT, Buontempo S, Cavallo N, Di Guida S, Fabozzi F, Iorio AOM, Lista L, Meola S, Merola M, Paolucci P, Azzi P, Bacchetta N, Bisello D, Branca A, Carlin R, Checchia P, Dall'Osso M, Dorigo T, Galanti M, Gasparini U, Giubilato P, Gozzelino A, Kanishchev K, Lacaprara S, Margoni M, Meneguzzo AT, Pazzini J, Pozzobon N, Ronchese P, Simonetto F, Torassa E, Tosi M, Vanini S, Ventura S, Zotto P, Zucchetta A, Zumerle G, Gabusi M, Ratti SP, Re V, Riccardi C, Salvini P, Vitulo P, Biasini M, Bilei GM, Ciangottini D, Fano L, Lariccia P, Mantovani G, Menichelli M, Saha A, Santocchia A, Spiezia A, Androsov K, Azzurri P, Bagliesi G, Bernardini J, Boccali T, Broccolo G, Castaldi R, Ciocci MA, Dell'Orso R, Donato S, Fiori F, Foa L, Giassi A, Grippo MT, Ligabue F, Lomtadze T, Martini L, Messineo A, Moon CS, Palla F, Rizzi A, Savoy-Navarro A, Serban AT, Spagnolo P, Squillacioti P, Tenchini R, Tonelli G, Venturi A, Verdini PG, Vernieri C, Barone L, Cavallari F, D'imperio G, Del Re D, Diemoz M, Jorda C, Longo E, Margaroli F, Meridiani P, Micheli F, Nourbakhsh S, Organtini G, Paramatti R, Rahatlou S, Rovelli C, Santanastasio F, Soffi L, Traczyk P, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Bellan R, Biino C, Cartiglia N, Casasso S, Costa M, Degano A, Demaria N, Finco L, Mariotti C, Maselli S, Migliore E, Monaco V, Musich M, Obertino MM, Ortona G, Pacher L, Pastrone N, Pelliccioni M, Angioni GLP, Potenza A, Romero A, Ruspa M, Sacchi R, Solano A, Staiano A, Tamponi U, Belforte S, Candelise V, Casarsa M, Cossutti F, Della Ricca G, Gobbo B, La Licata C, Marone M, Schizzi A, Umer T, Zanetti A, Chang S, Kropivnitskaya A, Nam SK, Kim DH, Kim GN, Kim MS, Kong DJ, Lee S, Oh YD, Park H, Sakharov A, Son DC, Kim TJ, Kim JY, Song S, Choi S, Gyun D, Hong B, Jo M, Kim H, Kim Y, Lee B, Lee KS, Park SK, Roh Y, Choi M, Kim JH, Park IC, Ryu G, Ryu MS, Choi Y, Choi YK, Goh J, Kim D, Kwon E, Lee J, Seo H, Yu I, Juodagalvis A, Komaragiri JR, Ali MABM, Linares EC, Castilla-Valdez H, De La Cruz-Burelo E, Heredia-de La Cruz I, Hernandez-Almada A, Lopez-Fernandez R, Sanchez-Hernandez A, Moreno SC, Valencia FV, Pedraza I, Ibarguen HAS, Pineda AM, Krofcheck D, Butler PH, Reucroft S, Ahmad A, Ahmad M, Hassan Q, Hoorani HR, Khan WA, Khurshid T, Shoaib M, Bialkowska H, Bluj M, Boimska B, Frueboes T, Gorski M, Kazana M, Nawrocki K, Romanowska-Rybinska K, Szleper M, Zalewski P, Brona G, Bunkowski K, Cwiok M, Dominik W, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Olszewski M, Wolszczak W, Bargassa P, Silva CBDE, Faccioli P, Parracho PGF, Gallinaro M, Iglesias LL, Nguyen F, Antunes JR, Seixas J, Varela J, Vischia P, Afanasiev S, Bunin P, Golutvin I, Karjavin V, Konoplyanikov V, Kozlov G, Lanev A, Malakhov A, Matveev V, Moisenz P, Palichik V, Perelygin V, Savina M, Shmatov S, Shulha S, Skatchkov N, Smirnov V, Zarubin A, Golovtsov V, Ivanov Y, Kim V, Levchenko P, Murzin V, Oreshkin V, Smirnov I, Sulimov V, Uvarov L, Vavilov S, Vorobyev A, Vorobyev A, Andreev Y, Dermenev A, Gninenko S, Golubev N, Kirsanov M, Krasnikov N, Pashenkov A, Tlisov D, Toropin A, Epshteyn V, Gavrilov V, Lychkovskaya N, Popov V, Pozdnyakov I, Safronov G, Semenov S, Spiridonov A, Stolin V, Vlasov E, Zhokin A, Andreev V, Azarkin M, Dremin I, Kirakosyan M, Leonidov A, Mesyats G, Rusakov SV, Vinogradov A, Belyaev A, Boos E, Bunichev V, Dubinin M, Dudko L, Ershov A, Gribushin A, Klyukhin V, Kodolova O, Lokhtin I, Obraztsov S, Savrin V, Snigirev A, Azhgirey I, Bayshev I, Bitioukov S, Kachanov V, Kalinin A, Konstantinov D, Krychkine V, Petrov V, Ryutin R, Sobol A, Tourtchanovitch L, Troshin S, Tyurin N, Uzunian A, Volkov A, Adzic P, Ekmedzic M, Milosevic J, Rekovic V, Maestre JA, Battilana C, Calvo E, Cerrada M, Llatas MC, Colino N, Delacruz B, Peris AD, Vazquez DD, Del Valle AE, Bedoya CF, Ramos JPF, Flix J, Fouz MC, Garcia-Abia P, Lopez OG, Lopez SG, Hernandez JM, Josa MI, De Martino EN, Yzquierdo APC, Pelayo JP, Olmeda AQ, Redondo I, Romero L, Soares MS, Albajar C, de Troconiz JF, Missiroli M, Moran D, Brun H, Cuevas J, Menendez JF, Folgueras S, Caballero IG, Cifuentes JAB, Cabrillo IJ, Calderon A, Campderros JD, Fernandez M, Gomez G, Graziano A, Virto AL, Marco JMR, Rivero CM, Matorras F, Sanchez FJM, Gomez JP, Rodrigo T, Rodriguez-Marrero AY, Ruiz-Jimeno A, Scodellaro L, Vila I, Cortabitarte RV, Abbaneo D, Auffray E, Auzinger G, Bachtis M, Baillon P, Ball AH, Barney D, Benaglia A, Bendavid J, Benhabib L, Benitez JF, Bernet C, Bloch P, Bocci A, Bonato A, Bondu O, Botta C, Breuker H, Camporesi T, Cerminara G, Colafranceschi S, D'Alfonso M, d'Enterria D, Dabrowski A, David A, De Guio F, De Roeck A, De Visscher S, Di Marco E, Dobson M, Dordevic M, Dupont-Sagorin N, Elliott-Peisert A, Eugster J, Franzoni G, Funk W, Gigi D, Gill K, Giordano D, Girone M, Glege F, Guida R, Gundacker S, Guthoff M, Hammer J, Hansen M, Harris P, Hegeman J, Innocente V, Janot P, Kousouris K, Krajczar K, Lecoq P, Lourenco C, Magini N, Malgeri L, Mannelli M, Marrouche J, Masetti L, Meijers F, Mersi S, Meschi E, Moortgat F, Morovic S, Mulders M, Musella P, Orsini L, Pape L, Perez E, Perrozzi L, Petrilli A, Petrucciani G, Pfeiffer A, Pierini M, Pimia M, Piparo D, Plagge M, Racz A, Rolandi G, Rovere M, Sakulin H, Schafer C, Schwick C, Sharma A, Siegrist P, Silva P, Simon M, Sphicas P, Spiga D, Steggemann J, Stieger B, Stoye M, Takahashi Y, Treille D, Tsirou A, Veres GI, Wardle N, Wohri HK, Wollny H, Zeuner WD, Bertl W, Deiters K, Erdmann W, Horisberger R, Ingram Q, Kaestli HC, Kotlinski D, Langenegger U, Renker D, Rohe T, Bachmair F, Bani L, Bianchini L, Buchmann MA, Casal B, Chanon N, Dissertori G, Dittmar M, Donega M, Dunser M, Eller P, Grab C, Hits D, Hoss J, Lustermann W, Mangano B, Marini AC, del Arbol PMR, Masciovecchio M, Meister D, Mohr N, Nageli C, Nessi-Tedaldi F, Pandolfi F, Pauss F, Peruzzi M, Quittnat M, Rebane L, Rossini M, Starodumov A, Takahashi M, Theofilatos K, Wallny R, Weber HA, Amsler C, Canelli MF, Chiochia V, De Cosa A, Hinzmann A, Hreus T, Kilminster B, Lange C, Mejias BM, Ngadiuba J, Robmann P, Ronga FJ, Taroni S, Verzetti M, Yang Y, Cardaci M, Chen KH, Ferro C, Kuo CM, Lin W, Lu YJ, Volpe R, Yu SS, Chang P, Chang YH, Chang YW, Chao Y, Chen KF, Chen PH, Dietz C, Grundler U, Hou WS, Kao KY, Liu YF, Lu RS, Majumder D, Petrakou E, Tzeng YM, Wilken R, Asavapibhop B, Singh G, Srimanobhas N, Suwonjandee N, Adiguzel A, Bakirci MN, Cerci S, Dozen C, Dumanoglu I, Eskut E, Girgis S, Gokbulut G, Gurpinar E, Hos I, Kangal EE, Topaksu AK, Onengut G, Ozdemir K, Ozturk S, Polatoz A, Cerci DS, Tali B, Topakli H, Vergili M, Akin IV, Bilin B, Bilmis S, Gamsizkan H, Isildak B, Karapinar G, Ocalan K, Sekmen S, Surat UE, Yalvac M, Zeyrek M, Albayrak EA, Gulmez E, Kaya M, Kaya O, Yetkin T, Cankocak K, Vardarli FI, Levchuk L, Sorokin P, Brooke JJ, Clement E, Cussans D, Flacher H, Goldstein J, Grimes M, Heath GP, Heath HF, Jacob J, Kreczko L, Lucas C, Meng Z, Newbold DM, Paramesvaran S, Poll A, Sakuma T, Senkin S, Smith VJ, Williams T, Bell KW, Belyaev A, Brew C, Brown RM, Cockerill DJA, Coughlan JA, Harder K, Harper S, Olaiya E, Petyt D, Shepherd-Themistocleous CH, Thea A, Tomalin IR, Womersley WJ, Worm SD, Baber M, Bainbridge R, Buchmuller O, Burton D, Colling D, Cripps N, Cutajar M, Dauncey P, Davies G, Della Negra M, Dunne P, Ferguson W, Fulcher J, Futyan D, Hall G, Iles G, Jarvis M, Karapostoli G, Kenzie M, Lane R, Lucas R, Lyons L, Magnan AM, Malik S, Mathias B, Nash J, Nikitenko A, Pela J, Pesaresi M, Petridis K, Raymond DM, Rogerson S, Rose A, Seez C, Sharp P, Tapper A, Acosta MV, Virdee T, Zenz SC, Cole JE, Hobson PR, Khan A, Kyberd P, Leggat D, Leslie D, Martin W, Reid ID, Symonds P, Teodorescu L, Turner M, Dittmann J, Hatakeyama K, Kasmi A, Liu H, Scarborough T, Charaf O, Cooper SI, Henderson C, Rumerio P, Avetisyan A, Bose T, Fantasia C, Lawson P, Richardson C, Rohlf J, St John J, Sulak L, Alimena J, Berry E, Bhattacharya S, Christopher G, Cutts D, Demiragli Z, Dhingra N, Ferapontov A, Garabedian A, Heintz U, Kukartsev G, Laird E, Landsberg G, Luk M, Narain M, Segala M, Sinthuprasith T, Speer T, Swanson J, Breedon R, Breto G, Sanchez MCD, Chauhan S, Chertok M, Conway J, Conway R, Cox PT, Erbacher R, Gardner M, Ko W, Lander R, Miceli T, Mulhearn M, Pellett D, Pilot J, Ricci-Tam F, Searle M, Shalhout S, Smith J, Squires M, Stolp D, Tripathi M, Wilbur S, Yohay R, Cousins R, Everaerts P, Farrell C, Hauser J, Ignatenko M, Rakness G, Takasugi E, Valuev V, Weber M, Burt K, Clare R, Ellison J, Gary JW, Hanson G, Heilman J, Rikova MI, Jandir P, Kennedy E, Lacroix F, Long OR, Luthra A, Malberti M, Negrete MO, Shrinivas A, Sumowidagdo S, Wimpenny S, Branson JG, Cerati GB, Cittolin S, D'Agnolo RT, Holzner A, Kelley R, Klein D, Letts J, Macneill I, Olivito D, Padhi S, Palmer C, Pieri M, Sani M, Sharma V, Simon S, Sudano E, Tadel M, Tu Y, Vartak A, Welke C, Wurthwein F, Yagil A, Barge D, Bradmiller-Feld J, Campagnari C, Danielson T, Dishaw A, Dutta V, Flowers K, Sevilla MF, Geffert P, George C, Golf F, Gouskos L, Incandela J, Justus C, Mccoll N, Richman J, Stuart D, To W, West C, Yoo J, Apresyan A, Bornheim A, Bunn J, Chen Y, Duarte J, Mott A, Newman HB, Pena C, Rogan C, Spiropulu M, Timciuc V, Vlimant JR, Wilkinson R, Xie S, Zhu RY, Azzolini V, Calamba A, Carlson B, Ferguson T, Iiyama Y, Paulini M, Russ J, Vogel H, Vorobiev I, Cumalat JP, Ford WT, Gaz A, Krohn M, Lopez EL, Nauenberg U, Smith JG, Stenson K, Ulmer KA, Wagner SR, Alexander J, Chatterjee A, Chaves J, Chu J, Dittmer S, Eggert N, Mirman N, Kaufman GN, Patterson JR, Ryd A, Salvati E, Skinnari L, Sun W, Teo WD, Thom J, Thompson J, Tucker J, Weng Y, Winstrom L, Wittich P, Winn D, Abdullin S, Albrow M, Anderson J, Apollinari G, Bauerdick LAT, Beretvas A, Berryhill J, Bhat PC, Bolla G, Burkett K, Butler JN, Cheung HWK, Chlebana F, Cihangir S, Elvira VD, Fisk I, Freeman J, Gao Y, Gottschalk E, Gray L, Green D, Grunendahl S, Gutsche O, Hanlon J, Hare D, Harris RM, Hirschauer J, Hooberman B, Jindariani S, Johnson M, Joshi U, Kaadze K, Klima B, Kreis B, Kwan S, Linacre J, Lincoln D, Lipton R, Liu T, Lykken J, Maeshima K, Marraffino JM, Outschoorn VIM, Maruyama S, Mason D, McBride P, Merkel P, Mishra K, Mrenna S, Musienko Y, Nahn S, Newman-Holmes C, O'Dell V, Prokofyev O, Sexton-Kennedy E, Sharma S, Soha A, Spalding WJ, Spiegel L, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vidal R, Whitbeck A, Whitmore J, Yang F, Acosta D, Avery P, Bortignon P, Bourilkov D, Carver M, Curry D, Das S, De Gruttola M, Di Giovanni GP, Field RD, Fisher M, Furic IK, Hugon J, Konigsberg J, Korytov A, Kypreos T, Low JF, Matchev K, Milenovic P, Mitselmakher G, Muniz L, Rinkevicius A, Shchutska L, Snowball M, Sperka D, Yelton J, Zakaria M, Hewamanage S, Linn S, Markowitz P, Martinez G, Rodriguez JL, Adams T, Askew A, Bochenek J, Diamond B, Haas J, Hagopian S, Hagopian V, Johnson KF, Prosper H, Veeraraghavan V, Weinberg M, Baarmand MM, Hohlmann M, Kalakhety H, Yumiceva F, Adams MR, Apanasevich L, Bazterra VE, Berry D, Betts RR, Bucinskaite I, Cavanaugh R, Evdokimov O, Gauthier L, Gerber CE, Hofman DJ, Khalatyan S, Kurt P, Moon DH, O'Brien C, Silkworth C, Turner P, Varelas N, Bilki B, Clarida W, Dilsiz K, Duru F, Haytmyradov M, Merlo JP, Mermerkaya H, Mestvirishvili A, Moeller A, Nachtman J, Ogul H, Onel Y, Ozok F, Penzo A, Rahmat R, Sen S, Tan P, Tiras E, Wetzel J, Yi K, Barnett BA, Blumenfeld B, Bolognesi S, Fehling D, Gritsan AV, Maksimovic P, Martin C, Swartz M, Baringer P, Bean A, Benelli G, Bruner C, Kenny RP, Malek M, Murray M, Noonan D, Sanders S, Sekaric J, Stringer R, Wang Q, Wood JS, Chakaberia I, Ivanov A, Khalil S, Makouski M, Maravin Y, Saini LK, Shrestha S, Skhirtladze N, Svintradze I, Gronberg J, Lange D, Rebassoo F, Wright D, Baden A, Belloni A, Calvert B, Eno SC, Gomez JA, Hadley NJ, Kellogg RG, Kolberg T, Lu Y, Marionneau M, Mignerey AC, Pedro K, Skuja A, Tonjes MB, Tonwar SC, Apyan A, Barbieri R, Bauer G, Busza W, Cali IA, Chan M, Di Matteo L, Ceballos GG, Goncharov M, Gulhan D, Klute M, Lai YS, Lee YJ, Levin A, Luckey PD, Ma T, Paus C, Ralph D, Roland C, Roland G, Stephans GSF, Stockli F, Sumorok K, Velicanu D, Veverka J, Wyslouch B, Yang M, Zanetti M, Zhukova V, Dahmes B, Gude A, Kao SC, Klapoetke K, Kubota Y, Mans J, Pastika N, Rusack R, Singovsky A, Tambe N, Turkewitz J, Acosta JG, Oliveros S, Avdeeva E, Bloom K, Bose S, Claes DR, Dominguez A, Suarez RG, Keller J, Knowlton D, Kravchenko I, Lazo-Flores J, Malik S, Meier F, Ratnikov F, Snow GR, Zvada M, Dolen J, Godshalk A, Iashvili I, Kharchilava A, Kumar A, Rappoccio S, Alverson G, Barberis E, Baumgartel D, Chasco M, Haley J, Massironi A, Morse DM, Nash D, Orimoto T, Trocino D, Wang RJ, Wood D, Zhang J, Hahn KA, Kubik A, Mucia N, Odell N, Pollack B, Pozdnyakov A, Schmitt M, Stoynev S, Sung K, Velasco M, Won S, Brinkerhoff A, Chan KM, Drozdetskiy A, Hildreth M, Jessop C, Karmgard DJ, Kellams N, Lannon K, Luo W, Lynch S, Marinelli N, Pearson T, Planer M, Ruchti R, Valls N, Wayne M, Wolf M, Woodard A, Antonelli L, Brinson J, Bylsma B, Durkin LS, Flowers S, Hart A, Hill C, Hughes R, Kotov K, Ling TY, Puigh D, Rodenburg M, Smith G, Winer BL, Wolfe H, Wulsin HW, Driga O, Elmer P, Hardenbrook J, Hebda P, Hunt A, Koay SA, Lujan P, Marlow D, Medvedeva T, Mooney M, Olsen J, Piroue P, Quan X, Saka H, Stickland D, Tully C, Werner JS, Zuranski A, Brownson E, Mendez H, Vargas ER, Barnes VE, Benedetti D, Bortoletto D, De Mattia M, Gutay L, Hu Z, Jha MK, Jones M, Jung K, Kress M, Leonardo N, Pegna DL, Maroussov V, Miller DH, Neumeister N, Radburn-Smith BC, Shi X, Shipsey I, Silvers D, Svyatkovskiy A, Wang F, Xie W, Xu L, Yoo HD, Zablocki J, Zheng Y, Parashar N, Stupak J, Adair A, Akgun B, Ecklund KM, Geurts FJM, Li W, Michlin B, Padley BP, Redjimi R, Roberts J, Zabel J, Betchart B, Bodek A, Covarelli R, de Barbaro P, Demina R, Eshaq Y, Ferbel T, Garcia-Bellido A, Goldenzweig P, Han J, Harel A, Khukhunaishvili A, Korjenevski S, Petrillo G, Vishnevskiy D, Ciesielski R, Demortier L, Goulianos K, Lungu G, Mesropian C, Arora S, Barker A, Chou JP, Contreras-Campana C, Contreras-Campana E, Duggan D, Ferencek D, Gershtein Y, Gray R, Halkiadakis E, Hidas D, Kaplan S, Lath A, Panwalkar S, Park M, Patel R, Salur S, Schnetzer S, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Rose K, Spanier S, York A, Bouhali O, Hernandez AC, Eusebi R, Flanagan W, Gilmore J, Kamon T, Khotilovich V, Krutelyov V, Montalvo R, Osipenkov I, Pakhotin Y, Perloff A, Roe J, Rose A, Safonov A, Suarez I, Tatarinov A, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero PR, Faulkner J, Kovitanggoon K, Kunori S, Lee SW, Libeiro T, Volobouev I, Appelt E, Delannoy AG, Greene S, Gurrola A, Johns W, Maguire C, Mao Y, Melo A, Sharma M, Sheldon P, Snook B, Tuo S, Velkovska J, Arenton MW, Boutle S, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Lin C, Neu C, Wood J, Clarke C, Harr R, Karchin PE, Don CKK, Lamichhane P, Sturdy J, Belknap DA, Carlsmith D, Cepeda M, Dasu S, Dodd L, Duric S, Friis E, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Lanaro A, Lazaridis C, Levine A, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ross I, Sarangi T, Savin A, Smith WH, Taylor D, Verwilligen P, Vuosalo C, Woods N
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Search for new phenomena in monophoton final states in proton-proton collisions at root s=8 TeV
PHYSICS LETTERS B 2016 APR 10; 755(?):102-124
Results are presented from a search for new physics in final states containing a photon and missing transverse momentum. The data correspond to an integrated luminosity of 19.6 fb(-1) collected in proton-proton collisions at root s = 8 TeV with the CMS experiment at the LHC. Nodeviation from the standard model predictions is observed for these final states. New, improved limits are set on dark matter production and on parameters of models with large extra dimensions. In particular, the first limits from the LHC on branon production are found and significantly extend previous limits from LEP and the Tevatron. An upper limit of 14.0 fb on the cross section is set at the 95% confidence level for events with a monophoton final state with photon transverse momentum greater than 145 GeV and missing transverse momentum greater than 140 GeV. (C) 2016 CERN for the benefit of the CMS Collaboration. Published by Elsevier B.V.
Jia MX, Lu H, Markowitz M, Cheng-Mayer C, Wu XL
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Development of Broadly Neutralizing Antibodies and Their Mapping by Monomeric gp120 in Human Immunodeficiency Virus Type 1-Infected Humans and Simian-Human Immunodeficiency Virus SHIVSF162P3N-Infected Macaques
JOURNAL OF VIROLOGY 2016 APR; 90(8):4017-4031
To improve our understanding of the similarities and differences between neutralizing antibodies elicited by simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and human immunodeficiency virus type 1 (HIV-1)-infected humans, we examined the plasma of 13 viremic macaques infected with SHIVSF162P3N and 85 HIV-1-infected humans with known times of infection. We identified 5 macaques (38%) from 1 to 2 years postinfection (p.i.) with broadly neutralizing antibodies (bnAbs) against tier 2 HIV-1. In comparison, only 2 out of 42 (5%) human plasma samples collected in a similar time frame of 1 to 3 years p.i. exhibited comparable neutralizing breadths and potencies, with the number increasing to 7 out of 21 (30%) after 3 years p.i. Plasma mapping with monomeric gp120 identified only 2 out of 9 humans and 2 out of 4 macaques that contained gp120-reactive neutralizing antibodies, indicating distinct specificities in these plasma samples, with most of them recognizing the envelope trimer (including gp41) rather than the gp120 monomer. Indeed, a total of 20 gp120-directed monoclonal antibodies (MAbs) isolated from a human subject (AD358) and a Chinese rhesus macaque (GB40) displayed no or limited neutralizing activity against tier 2 strains. These isolated MAbs, mapped to the CD4-binding site, the V3 loop, the inner domain, and the C5 region of gp120, revealed genetic similarity between the human and macaque immunoglobulin genes used to encode some V3-directed MAbs. These results also support the use of envelope trimer probes for efficient isolation of HIV-1 bnAbs. IMPORTANCE HIV-1 vaccine research can benefit from understanding the development of broadly neutralizing antibodies (bnAbs) in rhesus macaques, commonly used to assess vaccine immunogenicity and efficacy. Here, we examined 85 HIV-1-infected humans and 13 SHIVSF162P3N-infected macaques for bnAbs and found that, similar to HIV-1-infected humans, bnAbs in SHIV-infected macaques are also rare, but their development might have been faster in some of the studied macaques. Plasma mapping with monomeric gp120 indicated that most bnAbs bind to the envelope trimer rather than the gp120 monomer. In support of this, none of the isolated gp120-reactive monoclonal antibodies (MAbs) displayed the neutralization breadth observed in the corresponding plasma. However, the MAb sequences revealed similarity between human and macaque genes used to encode some V3-directed MAbs. Our study sheds light on the timing and development of bnAbs in SHIV-infected macaques in comparison to HIV-1-infected humans and highlights the use of envelope trimer probes for efficient recovery of bnAbs.
Takai H, Jenkinson E, Kabir S, Babul-Hirji R, Najm-Tehrani N, Chitayat DA, Crow YJ, de Lange T
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A POT1 mutation implicates defective telomere end fill-in and telomere truncations in Coats plus
GENES & DEVELOPMENT 2016 APR 1; 30(7):812-826
Coats plus (CP) can be caused by mutations in the CTC1 component of CST, which promotes polymerase a (pola)/primase- dependent fill-in throughout the genome and at telomeres. The cellular pathology relating to CP has not been established. We identified a homozygous POT1 S322L substitution (POT1(CP)) in two siblings with CP. POT1(CP) induced a proliferative arrest that could be bypassed by telomerase. POT1CP was expressed at normal levels, bound TPP1 and telomeres, and blocked ATR signaling. POT1(CP) was defective in regulating telomerase, leading to telomere elongation rather than the telomere shortening observed in other telomeropathies. POT1(CP) was also defective in the maintenance of the telomeric C strand, causing extended 3' overhangs and stochastic telomere truncations that could be healed by telomerase. Consistent with shortening of the telomeric C strand, metaphase chromosomes showed loss of telomeres synthesized by leading strand DNA synthesis. We propose that CP is caused by a defect in POT1/CST-dependent telomere fill-in. We further propose that deficiency in the fill-in step generates truncated telomeres that halt proliferation in cells lacking telomerase, whereas, in tissues expressing telomerase (e.g., bone marrow), the truncations are healed. The proposed etiology can explain why CP presents with features distinct from those associated with telomerase defects (e.g., dyskeratosis congenita).
Touhara KK, Wang WW, MacKinnon R
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The GIRK1 subunit potentiates G protein activation of cardiac GIRK1/4 hetero-tetramers
ELIFE 2016 APR 13; 5(?):? Article e15750
G protein gated inward rectifier potassium (GIRK) channels are gated by direct binding of G protein beta-gamma subunits (Gb gamma), signaling lipids, and intracellular Na+. In cardiac pacemaker cells, hetero-tetramer GIRK1/4 channels and homo-tetramer GIRK4 channels play a central role in parasympathetic slowing of heart rate. It is known that the Na+ binding site of the GIRK1 subunit is defective, but the functional difference between GIRK1/4 hetero-tetramers and GIRK4 homo-tetramers remains unclear. Here, using purified proteins and the lipid bilayer system, we characterize Gb gamma and Na+ regulation of GIRK1/4 hetero-tetramers and GIRK4 homo-tetramers. We find in GIRK4 homo-tetramers that Na+ binding increases Gb gamma affinity and thereby increases the GIRK4 responsiveness to G protein stimulation. GIRK1/4 hetero-tetramers are not activated by Na+, but rather are in a permanent state of high responsiveness to Gb gamma, suggesting that the GIRK1 subunit functions like a GIRK4 subunit with Na+ permanently bound.