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Kung A, Chen YC, Schimpl M, Ni F, Zhu JF, Turner M, Molina H, Overman R, Zhang C
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Development of Specific, Irreversible Inhibitors for a Receptor Tyrosine Kinase EphB3
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2016 AUG 24; 138(33):10554-10560
Erythropoietin-producing human hepatocellular carcinoma (Eph) receptor tyrosine kinases (RTKs) regulate a variety of dynamic cellular events, including cell protrusion, migration, proliferation, and cell fate determination. Small-molecule inhibitors of Eph kinases are valuable tools for dissecting the physiological and pathological roles of Eph. However, there is a lack of small-molecule inhibitors that are selective for individual Eph isoforms due to the high homology within the family. Herein, we report the development of the first potent and specific inhibitors of a single Eph isoform, EphB3. Through structural bioinformatic analysis, we identified a cysteine in the hinge region of the EphB3 kinase domain, a feature that is not shared with any other human kinases. We synthesized and characterized a series of electrophilic quinazolines to target this unique, reactive feature in EphB3. Some of the electrophilic quinazolines selectively and potently inhibited EphB3 both in vitro and in cells. Cocrystal structures of EphB3 in complex with two quinazolines confirmed the covalent linkage between the protein and the inhibitors. A "clickable" version of an optimized inhibitor was created and employed to verify specific target engagement in the whole proteome and to probe the extent and kinetics of target engagement of existing EphB3 inhibitors. Furthermore, we demonstrate that the autophosphorylation of EphB3 within the juxtamembrane region occurs in trans using a specific inhibitor. These exquisitely specific inhibitors will facilitate the dissection of EphB3's role in various biological processes and disease contribution.
Roosing S, Rosti RO, Rosti B, de Vrieze E, Silhavy JL, van Wijk E, Wakeling E, Gleeson JG
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Identification of a homozygous nonsense mutation in KIAA0556 in a consanguineous family displaying Joubert syndrome
HUMAN GENETICS 2016 AUG; 135(8):919-921
Joubert Syndrome (JS) is an inherited ciliopathy associated with mutations in genes essential in primary cilium function. Whole exome sequencing in a multiplex consanguineous family from India revealed a KIAA0556 homozygous single base pair deletion mutation (c.4420del; p.Met1474Cysfs*11). Knockdown of the gene in zebrafish resulted in a ciliopathy phenotype, rescued by co-injection of wildtype cDNA. Affected siblings present a mild and classical form of Joubert syndrome allowing for further delineation of the JS associated genotypic spectrum.
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M, Meinhard MT, Meister D, Micheli F, Musella P, Nessi-Tedaldi F, Pandolfi F, Pata J, Pauss F, Perrin G, Perrozzi L, Quittnat M, Rossini M, Schonenberger M, Starodumov A, Takahashi M, Tavolaro VR, Theofilatos K, Wallny R, Aarrestad TK, Amsler C, Caminada L, Canelli MF, Chiochia V, De Cosa A, Galloni C, Hinzmann A, Hreus T, Kilminster B, Lange C, Ngadiuba J, Pinna D, Rauco G, Robmann P, Salerno D, Yang Y, Chen KH, Doan TH, Jain S, Khurana R, Konyushikhin M, Kuo CM, Lin W, Lu YJ, Pozdnyakov A, Yu SS, Kumar A, Chang P, Chang YH, Chang YW, Chao Y, Chen KF, Chen PH, Dietz C, Fiori F, Grundler U, Hou WS, Hsiung Y, Liu YF, Lu RS, Moya MM, Petrakou E, Tsai JF, Tzeng YM, Asavapibhop B, Kovitanggoon K, Singh G, Srimanobhas N, Suwonjandee N, Adiguzel A, Damarseckin S, Demiroglu ZS, Dozen C, Dumanoglu I, Girgis S, Gokbulut G, Guler Y, Gurpinar E, Hos I, Kangal EE, Topaksu AK, Onengut G, Ozdemir K, Ozturk S, Cerci DS, Tali B, Topakli H, Zorbilmez C, Bilin B, Bilmis S, Isildak B, Karapinar G, Yalvac M, Zeyrek M, Gulmez E, Kaya M, Kaya O, Yetkin EA, Yetkin T, Cakir A, Cankocak K, Sen S, Vardarli FI, Grynyov B, Levchuk L, Sorokin P, Aggleton R, Ball F, Beck L, Brooke JJ, Burns D, Clement E, Cussans D, Flacher H, Goldstein J, Grimes M, Heath GP, Heath HF, Jacob J, Kreczko L, Lucas C, Meng Z, Newbold DM, Paramesvaran S, Poll A, Sakuma T, El Nasr-Storey SS, Senkin S, Smith D, Smith VJ, Bell KW, Belyaev A, Brew C, Brown RM, Calligaris L, Cieri D, Cockerill DJA, Coughlan JA, Harder K, Harper S, Olaiya E, Petyt D, Shepherd-Themistocleous CH, Thea A, Tomalin IR, Williams T, Worm SD, Baber M, Bainbridge R, Buchmuller O, Bundock A, Burton D, Casasso S, Citron M, Colling D, Corpe L, Dauncey P, Davies G, De Wit A, Della Negra M, Dunne P, Elwood A, Futyan D, Hall G, Iles G, Lane R, Lucas R, Lyons L, Magnan AM, Malik S, Nash J, Nikitenko A, Pela J, Pesaresi M, Raymond DM, Richards A, Rose A, Seez C, Tapper A, Uchida K, Acosta MV, Virdee T, Zenz SC, Cole JE, Hobson PR, Khan A, Kyberd P, Leslie D, Reid ID, Symonds P, Teodorescu L, Turner M, Borzou A, Call K, Dittmann J, Hatakeyama K, Liu H, Pastika N, Charaf O, Cooper SI, Henderson C, Rumerio P, Arcaro D, Avetisyan A, Bose T, Gastler D, Rankin D, Richardson C, Rohlf J, Sulak L, Zou D, Alimena J, Benelli G, Berry E, Cutts D, Ferapontov A, Garabedian A, Hakala J, Heintz U, Jesus O, Laird E, Landsberg G, Mao Z, Narain M, Piperov S, Sagir S, Syarif R, Breedon R, Breto G, Sanchez MCD, Chauhan S, Chertok M, Conway J, Conway R, Cox PT, Erbacher R, Funk G, Gardner M, Ko W, Lander R, Mclean C, Mulhearn M, Pellett D, Pilot J, Ricci-Tam F, Shalhout S, Smith J, Squires M, Stolp D, Tripathi M, Wilbur S, Yohay R, Cousins R, Everaerts P, Florent A, Hauser J, Ignatenko M, Saltzberg D, Takasugi E, Valuev V, Weber M, Burt K, Clare R, Ellison J, Gary JW, Hanson G, Heilman J, Paneva MI, Jandir P, Kennedy E, Lacroix F, Long OR, Malberti M, Negrete MO, Shrinivas A, Wei H, Wimpenny S, Yates BR, Branson JG, Cerati GB, Cittolin S, D'Agnolo RT, Derdzinski M, Holzner A, Kelley R, Klein D, Letts J, Macneill I, Olivito D, Padhi S, Pieri M, Sani M, Sharma V, Simon S, Tadel M, Vartak A, Wasserbaech S, Welke C, Wurthwein F, Yagil A, Della Porta GZ, Bradmiller-Feld J, Campagnari C, Dishaw A, Dutta V, Flowers K, Sevilla MF, Geffert P, George C, Golf F, Gouskos L, Gran J, Incandela J, Mccoll N, Mullin SD, Richman J, Stuart D, Suarez I, West C, Yoo J, Anderson D, Apresyan A, Bornheim A, Bunn J, Chen Y, Duarte J, Mott A, Newman HB, Pena C, Spiropulu M, Vlimant JR, Xie S, Zhu RY, Andrews MB, Azzolini V, Calamba A, Carlson B, Ferguson T, Paulini M, Russ J, Sun M, Vogel H, Vorobiev I, Cumalat JP, Ford WT, Gaz A, Jensen F, Johnson A, Krohn M, Mulholland T, Nauenberg U, Stenson K, Wagner SR, Alexander J, Chatterjee A, Chaves J, Chu J, Dittmer S, Eggert N, Mirman N, Kaufman GN, Patterson JR, Rinkevicius A, Ryd A, Skinnari L, Soffi L, Sun W, Tan SM, Teo WD, Thom J, Thompson J, Tucker J, Weng Y, Wittich P, Abdullin S, Albrow M, Apollinari G, Banerjee S, Bauerdick LAT, Beretvas A, Berryhill J, Bhat PC, Bolla G, Burkett K, Butler JN, Cheung HWK, Chlebana F, Cihangir S, Elvira VD, Fisk I, Freeman J, Gottschalk E, Gray L, Green D, Grunendahl S, Gutsche O, Hanlon J, Hare D, Harris RM, Hasegawa S, Hirschauer J, Hu Z, Jayatilaka B, Jindariani S, Johnson M, Joshi U, Klima B, Kreis B, Lammel S, Lewis J, Linacre J, Lincoln D, Lipton R, Liu T, De Sa RL, Lykken J, Maeshima K, Marraffino JM, Maruyama S, Mason D, McBride P, Merkel P, Mrenna S, Nahn S, Newman-Holmes C, O'Dell V, Pedro K, Prokofyev O, Rakness G, Sexton-Kennedy E, Soha A, Spalding WJ, Spiegel L, Stoynev S, Strobbe N, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vernieri C, Verzocchi M, Vidal R, Wang M, Weber HA, Whitbeck A, Acosta D, Avery P, Bortignon P, Bourilkov D, Brinkerhoff A, Carnes A, Carver M, Curry D, Das S, Field RD, Furic IK, Konigsberg J, Korytov A, Kotov K, Ma P, Matchev K, Mei H, Milenovic P, Mitselmakher G, Rank D, Rossin R, Shchutska L, Snowball M, Sperka D, Terentyev N, Thomas L, Wang J, Wang S, Yelton J, Linn S, Markowitz P, Martinez G, Rodriguez JL, Ackert A, Adams JR, Adams T, Askew A, Bein S, Bochenek J, Diamond B, Haas J, Hagopian S, Hagopian V, Johnson KF, Khatiwada A, Prosper H, Weinberg M, Baarmand MM, Bhopatkar V, Colafranceschi S, Hohlmann M, Kalakhety H, Noonan D, Roy T, Yumiceva F, Adams MR, Apanasevich L, Berry D, Betts RR, Bucinskaite I, Cavanaugh R, Evdokimov O, Gauthier L, Gerber CE, Hofman DJ, Kurt P, O'Brien C, Gonzalez IDS, Turner P, Varelas N, Wu Z, Zakaria M, Zhang J, Bilki B, Clarida W, Dilsiz K, Durgut S, Gandrajula RP, Haytmyradov M, Khristenko V, Merlo JP, Mermerkaya H, Mestvirishvili A, Moeller A, Nachtman J, Ogul H, Onel Y, Ozok F, Penzo A, Snyder C, Tiras E, Wetzel J, Yi K, Anderson I, Barnett BA, Blumenfeld B, Cocoros A, Eminizer N, Fehling D, Feng L, Gritsan AV, Maksimovic P, Osherson M, Roskes J, Sarica U, Swartz M, Xiao M, Xin Y, You C, Baringer P, Bean A, Bruner C, Kenny RP, Majumder D, Malek M, Mcbrayer W, Murray M, Sanders S, Stringer R, Wang Q, Ivanov A, Kaadze K, Khalil S, Makouski M, Maravin Y, Mohammadi A, Saini LK, Skhirtladze N, Toda S, Lange D, Rebassoo F, Wright D, Anelli C, Baden A, Baron O, Belloni A, Calvert B, Eno SC, Ferraioli C, Gomez JA, Hadley NJ, Jabeen S, Kellogg RG, Kolberg T, Kunkle J, Lu Y, Mignerey AC, Shin YH, Skuja A, Tonjes MB, Tonwar SC, Apyan A, Barbieri R, Baty A, Bi R, Bierwagen K, Brandt S, Busza W, Cali IA, Demiragli Z, Di Matteo L, Ceballos GG, Goncharov M, Gulhan D, Iiyama Y, Innocenti GM, Klute M, Kovalskyi D, Krajczar K, Lai YS, Lee YJ, Levin A, Luckey PD, Marini AC, Mcginn C, Mironov C, Narayanan S, Niu X, Paus C, Roland C, Roland G, Salfeld-Nebgen J, Stephans GSF, Sumorok K, Tatar K, Varma M, Velicanu D, Veverka J, Wang J, Wang TW, Wyslouch B, Yang M, Zhukova V, Benvenuti AC, Dahmes B, Evans A, Finkel A, Gude A, Hansen P, Kalafut S, Kao SC, Klapoetke K, Kubota Y, Lesko Z, Mans J, Nourbakhsh S, Ruckstuhl N, Rusack R, Tambe N, Turkewitz J, Acosta JG, Oliveros S, Avdeeva E, Bartek R, Bloom K, Bose S, Claes DR, Dominguez A, Fangmeier C, Suarez RG, Kamalieddin R, Knowlton D, Kravchenko I, Meier F, Monroy J, Ratnikov F, Siado JE, Snow GR, Alyari M, Dolen J, George J, Godshalk A, Harrington C, Iashvili I, Kaisen J, Kharchilava A, Kumar A, Rappoccio S, Roozbahani B, Alverson G, Barberis E, Baumgartel D, Chasco M, Hortiangtham A, Massironi A, Morse DM, Nash D, Orimoto T, De Lima RT, Trocino D, Wang RJ, Wood D, Zhang J, Bhattacharya S, Hahn KA, Kubik A, Low JF, Mucia N, Odell N, Pollack B, Schmitt M, Sung K, Trovato M, Velasco M, Dev N, Hildreth M, Jessop C, Karmgard DJ, Kellams N, Lannon K, Marinelli N, Meng F, Mueller C, Musienko Y, Planer M, Reinsvold A, Ruchti R, Rupprecht N, Smith G, Taroni S, Valls N, Wayne M, Wolf M, Woodard A, Antonelli L, Brinson J, Bylsma B, Durkin LS, Flowers S, Hart A, Hill C, Hughes R, Ji W, Ling TY, Liu B, Luo W, Puigh D, Rodenburg M, Winer BL, Wulsin HW, Driga O, Elmer P, Hardenbrook J, Hebda P, Koay SA, Lujan P, Marlow D, Medvedeva T, Mooney M, Olsen J, Palmer C, Piroue P, Stickland D, Tully C, Zuranski A, Malik S, Barker A, Barnes VE, Benedetti D, Bortoletto D, Gutay L, Jha MK, Jones M, Jung AW, Jung K, Kumar A, Miller DH, Neumeister N, Radburn-Smith BC, Shi X, Shipsey I, Silvers D, Sun J, Svyatkovskiy A, Wang F, Xie W, Xu L, Parashar N, Stupak J, Adair A, Akgun B, Chen Z, Ecklund KM, Geurts FJM, Guilbaud M, Li W, Michlin B, Northup M, Padley BP, Redjimi R, Roberts J, Rorie J, Tu Z, Zabel J, Betchart B, Bodek A, de Barbaro P, Demina R, Eshaq Y, Ferbel T, Galanti M, Garcia-Bellido A, Han J, Hindrichs O, Khukhunaishvili A, Lo KH, Tan P, Verzetti M, Ciesielski R, Chou JP, Contreras-Campana E, Ferencek D, Gershtein Y, Halkiadakis E, Heindl M, Hidas D, Hughes E, Kaplan S, Elayavalli RK, Lath A, Nash K, Saka H, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Foerster M, Riley G, Rose K, Spanier S, Thapa K, Bouhali O, Hernandez AC, Celik A, Dalchenko M, De Mattia M, Delgado A, Dildick S, Eusebi R, Gilmore J, Huang T, Kamon T, Krutelyov V, Mueller R, Osipenkov I, Pakhotin Y, Patel R, Perloff A, Rathjens D, Rose A, Safonov A, Tatarinov A, Ulmer KA, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero PR, Faulkner J, Kunori S, Lamichhane K, Lee SW, Libeiro T, Undleeb S, Volobouev I, Appelt E, Delannoy AG, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Mao Y, Melo A, Ni H, Sheldon P, Tuo S, Velkovska J, Xu Q, Arenton MW, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Neu C, Sinthuprasith T, Sun X, Wang Y, Wolfe E, Wood J, Xia F, Clarke C, Harr R, Karchin PE, Don CKK, Lamichhane P, Sturdy J, Belknap DA, Carlsmith D, Dasu S, Dodd L, Duric S, Gomber B, Grothe M, Herndon M, Herve A, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ruggles T, Sarangi T, Savin A, Sharma A, Smith N, Smith WH, Taylor D, Verwilligen P, Woods N
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Evidence for exclusive gamma gamma -> W (+) W (-) production and constraints on anomalous quartic gauge couplings in pp collisions at and 8 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2016 AUG 22; ?(8):? Article 119
A search for exclusive or quasi-exclusive gamma gamma -> W (+) W (-) production, via pp -> p ((*)) W (+) W (-) p ((*)) -> p ((*)) mu (+/-)e(a") p ((*)) at TeV, is reported using data corresponding to an integrated luminosity of 19.7 fb(-1). Events are selected by requiring the presence of an electron-muon pair with large transverse momentum p (T)(mu (+/-)e(a")) > 30 GeV, and no associated charged particles detected from the same vertex. The 8 TeV results are combined with the previous 7 TeV results (obtained for 5.05 fb(-1) of data). In the signal region, 13 (2) events are observed over an expected background of 3.9 +/- 0.6 (0.84 +/- 0.15) events for 8 (7) TeV, resulting in a combined excess of 3.4 sigma over the background-only hypothesis. The observed yields and kinematic distributions are compatible with the standard model prediction for exclusive and quasi-exclusive gamma gamma -> W (+) W (-) production. Upper limits on the anomalous quartic gauge coupling operators a (0,C) (W) (dimension-6) and f (M0,1,2,3) (dimension-8), the most stringent to date, are derived from the measured dilepton transverse momentum spectrum.
Chou HT, Dukovski D, Chambers MG, Reinisch KM, Walz T
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CATCHR, HOPS and CORVET tethering complexes share a similar architecture
NATURE STRUCTURAL & MOLECULAR BIOLOGY 2016 AUG; 23(8):761-763
We show here that the Saccharomyces cerevisiae GARP complex and the Cog1-4 subcomplex of the COG complex, both members of the complexes associated with tethering containing helical rods (CATCHR) family of multisubunit tethering complexes, share the same subunit organization. We also show that HOPS, a tethering complex acting in the endolysosomal pathway, shares a similar architecture, thus suggesting that multisubunit tethering complexes use related structural frameworks.
Alarcon CR, Tavazoie SF
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Endothelial-cell killing promotes metastasis
NATURE 2016 AUG 11; 536(7615):154-155
Van Kempen TA, Narayan A, Waters EM, Marques-Lopes J, Iadecola C, Glass MJ, Pickel VM, Milner TA
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Alterations in the Subcellular Distribution of NADPH Oxidase p47(phox) in Hypothalamic Paraventricular Neurons Following Slow-Pressor Angiotensin II Hypertension in Female Mice With Accelerated Ovarian Failure
JOURNAL OF COMPARATIVE NEUROLOGY 2016 AUG 1; 524(11):2251-2265
At younger ages, women have a lower risk for hypertension than men, but this sexual dimorphism declines with the onset of menopause. These differences are paralleled in rodents following "slow-pressor" angiotensin II (AngII) administration: young male and aged female mice, but not young females, develop hypertension. There is also an established sexual dimorphism both in the cardiovascular response to the neurohypophyseal hormone arginine vasopressin (AVP) and in the expression of oxidative stress. We examined the relationship between AngII-mediated hypertension and the cellular distribution of the superoxide generating NADPH oxidase (NOX) in AVP-expressing hypothalamic paraventricular nucleus (PVN) neurons in "menopausal" female mice. Dual-labeling immunoelectron microscopy was used to determine whether the subcellular distribution of the organizer/adapter NOX p47(phox) subunit is altered in PVN dendrites following AngII administered (14 days) during the "postmenopausal" stage of accelerated ovarian failure (AOF) in young female mice treated with 4-vinylcyclohexene diepoxide. Slow-pressor AngII elevated blood pressure in AOF females and induced a significant increase in near plasmalemmal p47(phox) and a decrease in cytoplasmic p47(phox) in PVN AVP dendrites. These changes are the opposite of those observed in AngII-induced hypertensive male mice (Coleman et al. [2013] J. Neurosci. 33:4308-4316) and may be ascribed in part to baseline differences between young females and males in the near plasmalemmal p47(phox) on AVP dendrites seen in the present study. These findings highlight fundamental differences in the neural substrates of oxidative stress in the PVN associated with AngII hypertension in postmenopausal females compared with males. (C) 2015 Wiley Periodicals, Inc.
Bastia D, Srivastava P, Zaman S, Choudhury M, Mohanty BK, Bacal J, Langston LD, Pasero P, O'Donnell ME
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Phosphorylation of CMG helicase and Tof1 is required for programmed fork arrest (vol 113, pg E3639, 2016)
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2016 AUG 2; 113(31):E4577-E4577
Jin J, Kim SN, Liu XQ, Zhang HJ, Zhang C, Seo JS, Kim Y, Sun T
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miR-17-92 Cluster Regulates Adult Hippocampal Neurogenesis, Anxiety, and Depression
CELL REPORTS 2016 AUG 9; 16(6):1653-1663
Emerging evidence has shown that noncoding RNAs, particularly microRNAs (miRNAs), contribute to the pathogenesis of mood and anxiety disorders, although the molecular mechanisms are poorly understood. Here, we show that altered levels of miR17-92 in adult hippocampal neural progenitors have a significant impact on neurogenesis and anxiety and depression-related behaviors in mice. miR-1792 deletion in adult neural progenitors decreases neurogenesis in the dentate gyrus, while its overexpression increases neurogenesis. miR-17-92 affects neurogenesis by regulating genes in the glucocorticoid pathway, especially serum- and glucocorticoid- inducible protein kinase-1 (Sgk1). miR-17-92 knockout mice show anxiety-and depression-like behaviors, whereas miR-17-92 overexpressing mice exhibit anxiolytic and antidepression-like behaviors. Furthermore, we show that miR-17-92 expression in the adult mouse hippocampus responds to chronic stress, and miR-17-92 rescues proliferation defects induced by corticosterone in hippocampal neural progenitors. Our study uncovers a crucial role for miR-17-92 in adult neural progenitors through regulation of neurogenesis and anxiety-and depression-like behaviors.
Aaltonen T, Amerio S, Amidei D, Anastassov A, Annovi A, Antos J, Apollinari G, Appel JA, Arisawa T, Artikov A, Asaadi J, Ashmanskas W, Auerbach B, Aurisano A, Azfar F, Badgett W, Bae T, Barbaro-Galtieri A, Barnes VE, Barnett BA, Barria P, Bartos P, Bauce M, Bedeschi F, Behari S, Bellettini G, Bellinger J, Benjamin D, Beretvas A, Bhatti A, Bland KR, Blumenfeld B, Bocci A, Bodek A, Bortoletto D, Boudreau J, Boveia A, Brigliadori L, Bromberg C, Brucken E, Budagov J, Budd HS, Burkett K, Busetto G, Bussey P, Butti P, Buzatu A, Calamba A, Camarda S, Campanelli M, Canelli F, Carls B, Carlsmith D, Carosi R, Carrillo S, Casal B, Casarsa M, Castro A, Catastini P, Cauz D, Cavaliere V, Cavalli-Sforza M, Cerri A, Cerrito L, Chen YC, Chertok M, Chiarelli G, Chlachidze G, Cho K, Chokheli D, Clark A, Clarke C, Convery ME, Conway J, Corbo M, Cordelli M, Cox CA, Cox DJ, Cremonesi M, Cruz D, Cuevas J, Culbertson R, d'Ascenzo N, Datta M, De Barbaro P, Demortier L, Deninno M, Devoto F, d'Errico M, Di Canto A, Di Ruzza B, Dittmann JR, D'Onofrio M, Donati S, Dorigo M, Driutti A, Ebina K, Edgar R, Elagin A, Erbacher R, Errede S, Esham B, Eusebi R, Farrington S, Ramos JPF, Field R, Flanagan G, Forrest R, Franklin M, Freeman JC, Frisch H, Funakoshi Y, Garfinkel AF, Garosi P, Gerberich H, Gerchtein E, Giagu S, Giakoumopoulou V, Gibson K, Ginsburg CM, Giokaris N, Giromini P, Giurgiu G, Glagolev V, Glenzinski D, Gold M, Goldin D, Golossanov A, Gomez G, Gomez-Ceballos G, Goncharov M, Lopez OG, Gorelov I, Goshaw AT, Goulianos K, Gramellini E, Grinstein S, Grosso-Pilcher C, Group RC, da Costa JG, Hahn SR, Han JY, Happacher F, Hara K, Hare M, Harr RF, Harrington-Taber T, Hatakeyama K, Hays C, Heinrich J, Herndon M, Hocker A, Hong Z, Hopkins W, Hou S, Hughes RE, Husemann U, Huston J, Introzzi G, Iori M, Ivanov A, James E, Jang D, Jayatilaka B, Jeon EJ, Jindariani S, Jones M, Joo KK, Jun SY, Junk TR, Kambeitz M, Kamon T, Karchin PE, Kasmi A, Kato Y, Ketchum W, Keung J, Kilminster B, Kim DH, Kim HS, Kim JE, Kim MJ, Kim SB, Kim SH, Kim YK, Kim YJ, Kimura N, Kirby M, Knoepfel K, Kondo K, Kong DJ, Konigsberg J, Kotwal AV, Kreps M, Kroll J, Kruse M, Kuhr T, Kurata M, Laasanen AT, Lammel S, Lancaster M, Lannon K, Latino G, Lee HS, Lee JS, Leone S, Lewis JD, Limosani A, Lipeles E, Liu H, Liu Q, Liu T, Lockwitz S, Loginov A, Lucchesi D, Lueck J, Lujan P, Lukens P, Lungu G, Lys J, Lysak R, Madrak R, Maestro P, Malik S, Manca G, Manousakis-Katsikakis A, Margaroli F, Marino P, Martinez M, Matera K, Mattson ME, Mazzacane A, Mazzanti P, McNulty R, Mehta A, Mehtala P, Mesropian C, Miao T, Mietlicki D, Mitra A, Miyake H, Moed S, Moggi N, Moon CS, Moore R, Morello MJ, Mukherjee A, Muller T, Murat P, Mussini M, Nachtman J, Nagai Y, Naganoma J, Nakano I, Napier A, Nett J, Neu C, Nigmanov T, Nodulman L, Noh SY, Norniella O, Oakes L, Oh SH, Oh YD, Oksuzian I, Okusawa T, Orava R, Ortolan L, Pagliarone C, Palencia E, Palni P, Papadimitriou V, Parker W, Pauletta G, Paulini M, Paus C, Phillips TJ, Piacentino G, Pianori E, Pilot J, Pitts K, Plager C, Pondrom L, Poprocki S, Potamianos K, Prokoshin F, Pranko A, Ptohos F, Punzi G, Ranjan N, Fernandez IR, Renton P, Rescigno M, Riddick T, Rimondi F, Ristori L, Robson A, Rodriguez T, Rolli S, Ronzani M, Roser R, Rosner JL, Ruffini F, Ruiz A, Russ J, Rusu V, Safonov A, Sakumoto WK, Sakurai Y, Santi L, Sato K, Saveliev V, Savoy-Navarro A, Schlabach P, Schmidt EE, Schwarz T, Scodellaro L, Seidel S, Seiya Y, Semenov A, Sforza F, Shalhout SZ, Shears T, Shepard PF, Shimojima M, Shochet M, Shreyber-Tecker I, Simonenko A, Sinervo P, Sliwa K, Smith JR, Snider FD, Sorin V, Song H, Stancari M, Denis RS, Stelzer B, Stelzer-Chilton O, Stentz D, Strologas J, Sudo Y, Sukhanov A, Suslov I, Takemasa K, Takeuchi Y, Tang J, Tecchio M, Teng PK, Thom J, Thomson E, Thukral V, Toback D, Tokar S, Tollefson K, Tomura T, Tonelli D, Torre S, Torretta D, Totaro P, Trovato M, Ukegawa F, Uozumi S, Vazquez F, Velev G, Vellidis C, Vernieri C, Vidal M, Vilar R, Vizan J, Vogel M, Volpi G, Wagner P, Wallny R, Wang SM, Warburton A, Waters D, Wester WC, Whiteson D, Wicklund AB, Wilbur S, Williams HH, Wilson JS, Wilson P, Winer BL, Wittich P, Wolbers S, Wolfe H, Wright T, Wu X, Wu Z, Yamamoto K, Yamato D, Yang T, Yang UK, Yang YC, Yao WM, Yeh GP, Yi K, Yoh J, Yorita K, Yoshida T, Yu GB, Yu I, Zanetti AM, Zeng Y, Zhou C, Zucchelli S
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Measurement of the WW and WZ production cross section using final states with a charged lepton and heavy-flavor jets in the full CDF Run II data set
PHYSICAL REVIEW D 2016 AUG 23; 94(3):? Article 032008
We present a measurement of the total WW and WZ production cross sections in p (p) over bar collision at root s = 1.96 TeV, in a final state consistent with leptonic W boson decay and jets originating from heavy-flavor quarks from either a W or a Z boson decay. This analysis uses the full data set collected with the CDF II detector during Run II of the Tevatron collider, corresponding to an integrated luminosity of 9.4 fb(-1). An analysis of the dijet mass spectrum provides 3.7 sigma evidence of the summed production processes of either WW or WZ bosons with a measured total cross section of sigma(WW+WZ) = 13.7 +/- 3.9 pb. Independent measurements of the WW and WZ production cross sections are allowed by the different heavy- flavor decay patterns of the W and Z bosons and by the analysis of secondary- decay vertices reconstructed within heavy- flavor jets. The productions of WW and of WZ dibosons are independently seen with significances of 2.9s and 2.1s, respectively, with total cross sections of sigma(WW) = 9.4 +/- 4.2 pb and sigma(WZ) = 3.7(-2.2)(+2.5) pb. The measurements are consistent with standard- model predictions.
Kellogg EH, Howes S, Ti SC, Ramirez-Aportela E, Kapoor TM, Chacon P, Nogales E
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Near-atomic cryo-EM structure of PRC1 bound to the microtubule
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2016 AUG 23; 113(34):9430-9439
Proteins that associate with microtubules (MTs) are crucial to generate MT arrays and establish different cellular architectures. One example is PRC1 (protein regulator of cytokinesis 1), which cross-links antiparallel MTs and is essential for the completion of mitosis and cytokinesis. Here we describe a 4-angstrom-resolution cryo-EM structure of monomeric PRC1 bound to MTs. Residues in the spectrin domain of PRC1 contacting the MT are highly conserved and interact with the same pocket recognized by kinesin. We additionally found that PRC1 promotes MT assembly even in the presence of the MT stabilizer taxol. Interestingly, the angle of the spectrin domain on the MT surface corresponds to the previously observed cross-bridge angle between MTs cross-linked by full-length, dimeric PRC1. This finding, together with molecular dynamic simulations describing the intrinsic flexibility of PRC1, suggests that the MT-spectrin domain interface determines the geometry of the MT arrays cross-linked by PRC1.