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Leisico F, Vieira DV, Figueiredo TA, Silva M, Cabrita EJ, Sobral RG, Ludovice AM, Trincao J, Romao MJ, de Lencastre H, Santos-Silva T
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First insights of peptidoglycan amidation in Gram-positive bacteria - the high-resolution crystal structure of Staphylococcus aureus glutamine amidotransferase GatD
SCIENTIFIC REPORTS 2018 MAR 28; 8(?):? Article 5313
Gram-positive bacteria homeostasis and antibiotic resistance mechanisms are dependent on the intricate architecture of the cell wall, where amidated peptidoglycan plays an important role. The amidation reaction is carried out by the bi-enzymatic complex MurT-GatD, for which biochemical and structural information is very scarce. In this work, we report the first crystal structure of the glutamine amidotransferase member of this complex, GatD from Staphylococcus aureus, at 1.85 angstrom resolution. A glutamine molecule is found close to the active site funnel, hydrogen-bonded to the conserved R128. In vitro functional studies using H-1-NMR spectroscopy showed that S. aureus MurT-GatD complex has glutaminase activity even in the absence of lipid II, the MurT substrate. In addition, we produced R128A, C94A and H189A mutants, which were totally inactive for glutamine deamidation, revealing their essential role in substrate sequestration and catalytic reaction. GatD from S. aureus and other pathogenic bacteria share high identity to enzymes involved in cobalamin biosynthesis, which can be grouped in a new sub-family of glutamine amidotransferases. Given the ubiquitous presence of GatD, these results provide significant insights into the molecular basis of the so far undisclosed amidation mechanism, contributing to the development of alternative therapeutics to fight infections.
Insley P, Shaham S
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Automated C-elegans embryo alignments reveal brain neuropil position invariance despite lax cell body placement
PLOS ONE 2018 MAR 28; 13(3):? Article e0194861
The Caenorhabditis elegans cell lineage is nearly invariant. Whether this stereotyped cell division pattern promotes reproducibility in cell shapes/positions is not generally known, as manual spatiotemporal cell-shape/position alignments are labor-intensive, and fully-automated methods are not described. Here, we report automated algorithms for spatiotemporal alignments of C. elegans embryos from pre-morphogenesis to motor-activity initiation. We use sparsely-labeled green-fluorescent nuclei and a pan-nuclear red-fluorescent reporter to register consecutive imaging time points and compare embryos. Using our method, we monitor early assembly of the nerve-ring (NR) brain neuropil. While NR pioneer neurons exhibit reproducible growth kinetics and axon positions, cell-body placements are variable. Thus, pioneer-neuron axon locations, but not cell-body positions, are under selection. We also show that anterior NR displacement in cam-1/ROR Wnt-receptor mutants is not an early NR assembly defect. Our results demonstrate the utility of automated spatiotemporal alignments of C. elegans embryos, and uncover key principles guiding nervous-system development in this animal.
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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 ., Brochet S, Bruno G, 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 BB, 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, 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, Hernaandez 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, El-khateeb E, Elgammal S, Kamel AE, 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, Fontaine 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, Donckt MV, 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, 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, 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, Placakyte R, 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, Draeger AR, 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, Muller 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, Kesisoglou S, Panagiotou A, Saoulidou N, Evangelou I, Foudas C, Kokkas P, Mallios S, Manthos N, Papadopoulos I, Paradas E, Strologas J, Triantis FA, Csanad M, Filipovic N, Pasztor G, Bencze G, Hajdu C, Horvath D, Hunyadi A, Sikler F, Veszpremi V, Vesztergombi G, 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, Bhawandeep U, 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, Sharma V, Bhardwaj R, Bhattacharya R, Bhattacharya S, 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, Parida B, 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, Caputo 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, 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, Esposito M, Fabozzi F, Fienga F, Iorio AOM, Khan WA, Lanza G, 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, Manzano PD, Dorigo T, Dosselli U, Gasparini F, Gasparini U, Gozzelino A, Lacaprara S, Margoni M, Meneguzzo AT, Pozzobon N, Ronchese P, Rossin R, Simonetto F, Torassa E, Zanetti M, Zotto P, Zumerle G, Braghieri A, Fallavollita F, Magnani A, Montagna P, Ratti SP, Re V, Ressegotti M, Riccardi C, Salvini P, Vai I, Vitulo P, Solestizi LA, Biasini M, Bilei GM, Cecchi C, Ciangottini D, Fano L, Lariccia P, Leonardi R, Manoni E, Mantovani G, Mariani V, Menichelli M, Rossi A, Santocchia A, Spiga D, Androsov K, Azzurri P, Bagliesi G, Bernardini J, 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, Del Re D, Diemoz M, Gelli S, Longo E, Margaroli F, Marzocchi B, Meridiani P, Organtini G, Paramatti R, Preiato F, Rahatlou S, Rovelli C, Santanastasio F, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Bartosik N, Bellan R, Biino C, Cartiglia N, Cenna F, Costa M, Covarelli R, Degano A, Demaria N, Kiani B, Mariotti C, Maselli S, Migliore E, Monaco V, Monteil E, Monteno M, Obertino MM, Pacher L, Pastrone N, Pelliccioni M, Angioni GLP, 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, Ryu G, 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, Castilla-Valdez H, De La 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Smith C, Bartek R, Dominguez A, Buccilli A, Cooper SI, Henderson C, Rumerio P, West C, Arcaro D, Avetisyan A, Bose T, Gastler D, Rankin D, Richardson C, Rohlf J, Sulak L, Zou D, Benelli G, Cutts D, 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, 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, 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, Das S, 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, 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, Stringer R, 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, Benaglia A, 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, 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, Ledovskoy A, Li H, Neu C, Sinthuprasith T, Sun X, 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, Gomber 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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Search for electroweak production of charginos and neutralinos in multilepton final states in proton-proton collisions at root s=13 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2018 MAR 27; ?(3):? Article 166
Results are presented from a search for the direct electroweak production of charginos and neutralinos in signatures with either two or more leptons (electrons or muons) of the same electric charge, or with three or more leptons, which can include up to two hadronically decaying tau leptons. The results are based on a sample of proton proton collision data collected at root s = 13 TeV, recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of 35.9 fb(-1). The observed event yields are consistent with the expectations based on the standard model. The results are interpreted in simplified models of supersymmetry describing various scenarios for the production and decay of charginos and neutralinos. Depending on the model parameters chosen, mass values between 180 GeV and 1150 GeV are excluded at 95% CL. These results significantly extend the parameter space probed for these particles in searches at the LHC. In addition, results are presented in a form suitable for alternative theoretical interpretations.
Galea S, Vaughan RD
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Causes and Causes of Causes of Population Health: A Public Health of Consequence, March 2018
AMERICAN JOURNAL OF PUBLIC HEALTH 2018 MAR; 108(3):304-305
Katz M, Corson F, Iwanir S, Biron D, Shaham S
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Glia Modulate a Neuronal Circuit for Locomotion Suppression during Sleep in C. elegans
CELL REPORTS 2018 MAR 6; 22(10):2575-2583
Glia have been suggested to regulate sleep-like states in vertebrates and invertebrates alike. In the nematode Caenorhabditis elegans, sleep is associated with molting between larval stages. To understand if glia modulate neural circuits driving sleep in C. elegans larvae, we ablated the astrocyte-like CEPsh glia. We found that glia-ablated animals exhibit episodes of immobility preceding sleep, prolonged sleep, molting-independent short-duration locomotory pausing, and delayed development. CEPsh glia ensheath synapses between the sleep-associated ALA neuron and its postsynaptic partner AVE, a major locomotion interneuron. While AVE calcium transients normally correlate with head retraction, glia ablation results in prolonged calcium transients that are uncoupled from movement. Strikingly, all these glia ablation defects are suppressed by the ablation of ALA. Our results suggest that glia attenuate sleep-promoting inhibitory connections between ALA and AVE, uncovering specific roles for glia in sleep behavior. We propose that similar mechanisms may underlie glial roles in sleep in other animals.
Kang JY, Mishanina TV, Bellecourt MJ, Mooney RA, Darst SA, Landick R
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RNA Polymerase Accommodates a Pause RNA Hairpin by Global Conformational Rearrangements that Prolong Pausing
MOLECULAR CELL 2018 MAR 1; 69(5):802-815.e1
Sequence-specific pausing by RNA polymerase (RNAP) during transcription plays crucial and diverse roles in gene expression. In bacteria, RNA structures are thought to fold within the RNA exit channel of the RNAP and can increase pause lifetimes significantly. The biophysical mechanism of pausing is uncertain. We used single-particle cryo-EM to determine structures of paused complexes, including a 3.8-angstrom structure of an RNA hairpin-stabilized, paused RNAP that coordinates RNA folding in the his operon attenuation control region of E. coli. The structures revealed a half-translocated pause state (RNA post-translocated, DNA pre-translocated) that can explain transcriptional pausing and a global conformational change of RNAP that allosterically inhibits trigger loop folding and can explain pause hairpin action. Pause hairpin interactions with the RNAP RNA exit channel suggest how RNAP guides the formation of nascent RNA structures.
Xu BW, Cai L, Butler JM, Chen DL, Lu XD, Allison DF, Lu R, Rafii S, Parker JS, Zheng DY, Wang GG
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The Chromatin Remodeler BPTF Activates a Stemness Gene-Expression Program Essential for the Maintenance of Adult Hematopoietic Stem Cells
STEM CELL REPORTS 2018 MAR 13; 10(3):675-683
Self-renewal and differentiation of adult stem cells are tightly regulated partly through configuration of chromatin structure by chromatin remodelers. Using knockout mice, we here demonstrate that bromodomain PHD finger transcription factor (BPTF), a component of the nucleosome remodeling factor (NURF) chromatin-remodeling complex, is essential for maintaining the population size of hematopoietic stem/progenitor cells (HSPCs), including long-term hematopoietic stem cells (HSCs). Bptf-deficient HSCs are defective in reconstituted hematopoiesis, and hematopoietic-specific knockout of Bptf caused profound defects including bone marrow failure and anemia. Genome-wide transcriptome profiling revealed that BPTF loss caused downregulation of HSC-specific gene-expression programs, which contain several master transcription factors (Meis1, Pbx1, Mn1, and Lmo2) required for HSC maintenance and self-renewal. Furthermore, we show that BPTF potentiates the chromatin accessibility of key HSC "stemness'' genes. These results demonstrate an essential requirement of the chromatin remodeler BPTF and NURF for activation of "stemness'' gene-expression programs and proper function of adult HSCs.
Cunningham SD, Mokshagundam S, Chai H, Lewis JB, Levine J, Tobin JN, Ickovics JR
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Postpartum Depressive Symptoms: Gestational Weight Gain as a Risk Factor for Adolescents Who Are Overweight or Obese
JOURNAL OF MIDWIFERY & WOMENS HEALTH 2018 MAR-APR; 63(2):178-184
IntroductionObesity is a risk factor for adverse physical health outcomes during pregnancy. Much less is known about the association between obesity and maternal mental health. Evidence suggests that prenatal depression is associated with excessive weight gain during pregnancy and that this relationship may vary according to pregravid body mass index (BMI). Young women may be particularly vulnerable to postpartum depression. The objective of this study is to examine the association between prepregnancy BMI, gestational weight gain, and postpartum depressive symptoms among adolescents. MethodsParticipants were 505 pregnant adolescents aged 14 to 21 years followed during pregnancy and 6 months postpartum. Data were collected via interviews and medical record abstraction. Multilevel linear mixed models were used to test the association between excessive gestational weight gain as defined by National Academy of Medicine Guidelines and postpartum depressive symptoms measured via the validated Center for Epidemiologic Studies Depression (CES-D) scale. Analyses controlled for sociodemographic factors (maternal age, race, ethnicity, relationship status), health behaviors (nutrition, physical activity), prenatal depressive symptoms, and postpartum weight retention. ResultsPrepregnancy BMI was classified as follows: 11% underweight, 53% healthy weight, 19% overweight, and 18% obese. One-half (50%) of participants exceeded recommended guidelines for gestational weight gain. Adolescents with excessive gestational weight gain who entered pregnancy overweight or obese had significantly higher postpartum depressive symptoms (, 2.41; SE, 1.06 vs , 2.58; SE, 1.08, respectively; both P < .05) compared with those with healthy prepregnancy BMI and appropriate gestational weight gain. Adolescents who gained gestational weight within clinically recommended guidelines were not at risk for increased depressive symptoms. DiscussionAdolescents who enter pregnancy overweight or obese and experience excessive weight gain may be at increased risk for postpartum depressive symptoms. Health care providers should offer preventive interventions during pregnancy and the interconceptional period to support healthy weight gain and safeguard women's mental health.
Barnes CO, Gristick HB, Freund NT, Escolano A, Lyubimov AY, Hartweger H, West AP, Cohen AE, Nussenzweig MC, Bjorkman PJ
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Structural characterization of a highly-potent V3-glycan broadly neutralizing antibody bound to natively-glycosylated HIV-1 envelope
NATURE COMMUNICATIONS 2018 MAR 28; 9(?):? Article 1251
Broadly neutralizing antibodies (bNAbs) isolated from HIV-1-infected individuals inform HIV-1 vaccine design efforts. Developing bNAbs with increased efficacy requires understanding how antibodies interact with the native oligomannose and complex-type N- glycan shield that hides most protein epitopes on HIV-1 envelope ( Env). Here we present crystal structures, including a 3.8-angstrom X-ray free electron laser dataset, of natively glycosylated Env trimers complexed with BG18, the most potent V3/N332(gp120) glycan-targeting bNAb reported to date. Our structures show conserved contacts mediated by common D gene-encoded residues with the N332(gp120) glycan and the gp120 GDIR peptide motif, but a distinct Env-binding orientation relative to PGT121/10-1074 bNAbs. BG18's binding orientation provides additional contacts with N392(gp120) and N386(gp120) glycans near the V3-loop base and engages protein components of the V1-loop. The BG18-natively-glycosylated Env structures facilitate understanding of bNAb-glycan interactions critical for using V3/N332(gp120) bNAbs therapeutically and targeting their epitope for immunogen design.
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Combined search for electroweak production of charginos and neutralinos in proton-proton collisions at root s=13 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2018 MAR 27; ?(3):? Article 160
A statistical combination of several searches for the electroweak production of charginos and neutralinos is presented. All searches use proton-proton collision data at A root s = 13 TeV, recorded with the CMS detector at the LHC in 2016 and corresponding to an integrated luminosity of 35.9 fb(-1). In addition to the combination of previous searches, a targeted analysis requiring three or more charged leptons (electrons or muons) is presented, focusing on the challenging scenario in which the difference in mass between the two least massive neutralinos is approximately equal to the mass of the Z boson. The results are interpreted in simplified models of chargino-neutralino or neutralino pair production. For chargino-neutralino production, in the case when the lightest neutralino is massless, the combination yields an observed (expected) limit at the 95% confidence level on the chargino mass of up to 650 (570) GeV, improving upon the individual analysis limits by up to 40 GeV. If the mass difference between the two least massive neutralinos is approximately equal to the mass of the Z boson in the chargino-neutralino model, the targeted search requiring three or more leptons obtains observed and expected exclusion limits of around 225 GeV on the second neutralino mass and 125 GeV on the lightest neutralino mass, improving the observed limit by about 60 GeV in both masses compared to the previous CMS result. In the neutralino pair production model, the combined observed (expected) exclusion limit on the neutralino mass extends up to 650-750 (550-750) GeV, depending on the branching fraction assumed. This extends the observed exclusion achieved in the individual analyses by up to 200 GeV. The combined result additionally excludes some intermediate gaps in the mass coverage of the individual analyses.