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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.
Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, Brandstetter J, Brondolin E, Dragicevic M, Ero J, Flechl M, Friedl M, Fruhwirthl R, Ghete VM, Grossmann J, Hrubec J, Jeitlerl M, Konig A, Krammer N, Kratschmer I, Liko D, Madlener T, Mikulec I, Pree E, Rad N, Rohringer H, Schieckl J, Schofbeck R, Spanring M, Spitzbart D, Waltenberger W, Wittmann J, Wulzi CE, Zarucki M, Chekhovsky V, Mossolov V, Gonzalez JS, De Wolf EA, Di Croce D, Janssen X, Lauwers J, Van De Klundert M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Abu Zeid S, Blekman F, D'Hondt J, De Bruyn I, De Clercq J, Deroover K, Flouris G, Lontkovskyi D, Lowette S, Marchesini I, Moortgat S, Moreels L, Python Q, Skovpen K, Tavernier S, Van Doninck W, Van Mulders P, Van Parijs I, Beghin D, Brun H, Clerbaux B, De Lentdecker G, Delannoy H, Dorney B, Fasanella G, Favart L, Goldouzian R, Grebenyuk A, Lenzi T, Luetic J, Maerschalk T, Marinov A, Seva T, Starling E, Velde CV, Vanlaer P, Vannerom D, Yonamine R, Zenoni F, Zhang F, Cimmino A, Cornelis T, Dobur D, Fagot A, Gul M, Khvastunov I, Poyraz D, Roskas C, Salva S, Tytgat M, Verbeke W, Zaganidis N, Bakhshiansohi H, Bondu O, Brochet S, Bruno G, Caputo C, Caudron A, David P, De Visscher S, Delaere C, Delcourt M, Francois B, Giammanco A, Komm M, Krintiras G, Lemaitre V, Magitteri A, Mertens A, Musich M, Piotrzkowski K, Quertenmont L, Saggio A, Marono MV, Wertz S, Zobec J, Aida WL, Alves FL, Alves GA, Brito L, Martins MC, Hensel C, Moraes A, Pol ME, Teles PR, Das Chagas EBB, Carvalho W, Chinellato J, Coelho E, Da Costa EM, Da Silveira GG, Damiao DD, De Souza SF, Guativa LMH, Malbouisson H, De Almeida MM, Herrera CM, Mundim L, Nogima H, Rosas LJS, Santoro A, Sznajder A, Thiel M, 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, Sultanov G, Dimitrov A, Litov L, Pavlov B, Petkov P, Fang W, Gao X, Yuan L, Ahmad M, Bian JG, Chen GM, Chen HS, Chen M, Chen Y, Jiang CH, Leggat D, Liao H, Liu Z, Romeo F, Shaheen SM, Spiezia A, Tao J, Wang C, Wang Z, Yazgan E, Zhang H, Zhang S, Zhao J, Ban Y, Chen G, Li Q, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Avila C, Cabrera A, Montoya CAC, Sierra LFC, Florez C, Hernandez CFG, Alvarez JDR, Delgado MAS, 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, Abdelalim AA, Mohammed Y, Salama E, Dewanjee RK, Kadastik M, Perrini L, Raidal M, Tiko A, Veelken C, Eerola P, Kirschenmann H, Pekkanen J, Voutilainen M, Havukainen J, Heikkila JK, Jarvinen T, Karimaki V, Kinnunen R, Lampen T, Lassila-Perini K, Laurila S, Lehti S, Linden T, Luukka P, Siikonen H, Tuominen E, Tuominiemi J, Tuuva T, Besancon M, Couderc F, Dejardin M, Denegri D, Faure JL, Ferri F, Ganjour S, Ghosh S, Gras P, de Monchenault GH, Jarry P, Kucher I, Leloup C, Locci E, Machet M, Malcles J, Negro G, Rander J, Rosowsky A, Sahin MO, Titov M, Abdulsalam A, Amendola C, Antropov I, Baffioni S, Beaudette F, Busson P, Cadamuro L, Chariot C, de Cassagnac RG, Jo M, Lisniak S, Lobanov A, Blanco JM, Nguyen M, Ochando C, Ortona G, Paganini P, Pigard P, 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, Vander Donckt M, Viret S, Khvedelidze A, Tsamalaidze Z, Autermann C, Feld L, Kiesel MK, Klein K, Lipinski M, Preuten M, Schomakers C, Schulz J, Zhukov V, Albert A, Dietz-Laursonn E, Duchardt D, Endres M, Erdmann M, Erdweg S, Esch T, Fischer R, Guth A, Hamer M, Hebbeker T, Heidemann C, Hoepfner K, Knutzen S, Merschmeyer M, Meyer A, Millet P, Mukherjee S, Pook T, Radziej M, Reithler H, Rieger M, Scheuch F, Teyssier D, Thuer S, Flugge G, Kargoll B, Kress T, Kuensken A, 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, Luyando JMG, Grohsjean A, Gunnellini P, Guthoff M, Harb A, Hauk J, Hempel M, Jung H, 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 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Cakir A, Cankocak K, Koseoglu I, Grynyov B, Levchuk L, Ball F, Beck L, Brooke JJ, Burns D, Clement E, Cussans D, Davignon O, Flacher H, Goldstein J, Heath GP, Heath HF, Kreczko L, Newbold DM, Paramesvaran S, Sakuma T, El Nasr-Storey SS, Smith D, Smith VJ, Bell KW, Belyaev A, Brew C, Brown RM, Calligaris L, Cieri D, Cockerill DJA, Coughlan JA, Harder K, Harper S, Linacre J, Olaiya E, Petyt D, Shepherd-Themistocleous CH, Thea A, Tomalin IR, Williams T, Auzinger G, Bainbridge R, Borg J, Breeze S, Buchmuller O, Bundock A, Casasso S, Citron M, Colling D, Corpe L, Dauncey P, Davies G, De Wit A, Della Negra M, Di Maria R, Elwood A, Haddad Y, Hall G, Iles G, James T, Lane R, Laner C, Lyons L, Magnan AM, Malik S, Mastrolorenzo L, Matsushita T, Nash J, Nikitenko A, Palladino V, Pesaresi M, Raymond DM, Richards A, Rose A, Scott E, Seez C, Shtipliyski A, Summers S, Tapper A, Uchida K, Acosta MV, Virdee T, Wardle N, Winterbottom D, Wright J, Zenz SC, Cole JE, Hobson PR, Khan A, Kyberd P, Reid ID, Teodorescu L, Turner M, Zahid S, Borzou A, Call K, Dittmann J, Hatakeyama K, Liu H, Pastika N, Smith C, Bartek R, Dominguez A, Buccilli A, Cooper SI, Henderson C, Rumerio P, West C, Arcaro D, Avetisyan A, Bose T, Gastler D, Rankin D, Richardson C, Rohlf J, Sulak L, Zou D, Benelli G, Cutts D, Garabedian A, Hadley M, Hakala J, Heintz U, Hogan JM, Kwok KHM, Laird E, Landsberg G, Lee J, Mao Z, Narain M, Pazzini J, Piperov S, Sagir S, Syarif R, Yu D, Band R, Brainerd C, Breedon R, Burns D, Sanchez MCD, Chertok M, Conway J, Conway R, Cox PT, Erbacher R, Flores C, Funk G, Ko W, Lander R, Mclean C, Mulhearn M, Pellett D, Pilot J, Shalhout S, Shi M, Smith J, Stolp D, Tos K, Tripathi M, Wang Z, Bachtis M, Bravo C, Cousins R, Dasgupta A, Florent A, Hauser J, Ignatenko M, Mccoll N, Regnard S, Saltzberg D, Schnaible C, Valuev V, Bouvier E, Burt K, Clare R, Ellison J, Gary JW, Shirazi SMAG, Hanson G, Heilman J, Karapostoli G, Kennedy E, Lacroix F, Long OR, Negrete MO, Paneva MI, Si W, Wang L, Wei H, Wimpenny S, Yates BR, Branson JG, Cittolin S, Derdzinski M, Gerosa R, Gilbert D, 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, Golf F, Gouskos L, Heller R, Incandela J, Ovcharova A, Qu H, Richman J, Stuart D, Suarez I, Yoo J, Anderson D, 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, Quach D, Rinkevicius A, Ryd A, Skinnari L, Soffi L, Tan SM, Tao Z, Thom J, Tucker J, Wittich P, Zientek M, Abdullin S, Albrow M, Alyari 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, Mason D, McBride P, Merkel P, Mrenna S, Nahn S, O'Dell V, Pedro K, Prokofyev O, Rakness G, Ristori L, Schneider B, Sexton-Kennedy E, Soha A, Spalding WJ, Spiegel L, Stoynev S, Strait J, Strobbe N, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vernieri C, Verzocchi M, Vidal R, Wang M, Weber HA, Whitbeck A, Acosta D, Avery P, Bortignon P, Bourilkov D, Brinkerhoff A, Carnes A, Carver M, Curry D, Field RD, Furic IK, Gleyzer SV, Joshi BM, Konigsberg J, Korytov A, Kotov K, Ma P, Matchev K, Mei H, Mitselmakher G, Rank D, Shi K, Sperka D, Terentyev N, Thomas L, Wang J, Wang S, Yelton J, Joshi YR, Linn S, Markowitz P, Rodriguez JL, Ackert A, Adams T, Askew A, Hagopian S, Hagopian V, Johnson KF, Kolberg T, Martinez G, Perry T, Prosper H, Saha A, Santra A, Sharma V, Yohay R, Baarmand MM, Bhopatkar V, Colafranceschi S, Hohlmann M, Noonan D, Roy T, Yumiceva F, Adams MR, Apanasevich L, Berry D, Betts RR, Cavanaugh R, Chen X, Evdokimov O, Gerber CE, Hangal DA, Hofman DJ, Jung K, Kamin J, Gonzalez IDS, Tonjes MB, Trauger H, Varelas N, Wang H, Wu Z, Zhang J, Bilki B, Clarida W, Dilsiz K, Durgut S, Gandrajula RP, Haytmyradov M, Khristenko V, Merlo JP, Mermerkaya H, Mestvirishvili A, Moeller A, Nachtman J, Gu H, Onel Y, Ozok F, Penzo A, Snyder C, Tiras E, Wetzel J, Yi K, Blumenfeld B, Cocoros A, Eminizer N, Fehling D, Feng L, Gritsan AV, Maksimovic P, Roskes J, Sarica U, Swartz M, Xiao M, You C, Al-bataineh A, Baringer P, Bean A, Boren S, Bowen J, Castle J, Khalil S, Kropivnitskaya A, Majumder D, Mcbrayer W, Murray M, Royon C, Sanders S, Schmitz E, Takaki JDT, Wang Q, Ivanov A, Kaadze K, Maravin Y, Mohammadi A, Saini LK, Skhirtladze N, Toda S, Rebassoo F, Wright D, Anelli C, Baden A, Baron O, Belloni A, Eno SC, Feng Y, 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, Hu M, 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, Hiltbrand J, Kalafut S, Kubota Y, Lesko Z, Mans J, Nourbakhsh S, Ruckstuhl N, Rusack R, Turkewitz J, Wadud MA, 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, 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, Orimoto T, De Lima RT, Trocino D, Wood D, Bhattacharya S, Charaf O, Hahn KA, Mucia N, Odell N, Schmitt MH, Sung K, Trovato M, Velasco M, Dev N, Hildreth M, Anampa KH, Jessop C, Karmgard DJ, Kellams N, Lannon K, Li W, Loukas N, Marinelli N, Meng F, Mueller C, Musienko Y, Planer M, Reinsvold A, Ruchti R, Siddireddy P, Smith G, Taroni S, Wayne M, Wightman A, 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, Winer BL, Wulsin HW, Cooperstein S, Driga O, Elmer P, Hardenbrook J, Hebda P, Higginbotham S, Kalogeropoulos A, Lange D, Luo J, Marlow D, Mei K, Ojalvo I, Olsen J, Palmer C, Piroue P, Stickland D, Tully C, Malik S, Norberg S, Barker A, Barnes VE, Das S, Folgueras S, Gutay L, Jha MK, Jones M, Jung AW, Khatiwada A, Miller DH, Neumeister N, Peng CC, Qiu H, Schulte JF, Sun J, Wang F, Xie W, Cheng T, Parashar N, Stupak J, Adair A, Chen Z, Ecklund KM, Freed S, Geurts FJM, Guilbaud M, Kilpatrick M, Li W, Michlin B, Northup M, Padley BP, Roberts J, Rorie J, Shi W, Tu Z, Zabel J, Zhang A, 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, Degado 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, Mengke T, Muthumuni S, Peltola T, Undleeb S, Volobouev I, Wang Z, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Melo A, Ni H, Padeken K, Sheldon P, Tuo S, Velkovska J, Xu Q, Arenton MW, Barria P, Cox B, Hirosky R, Joyce M, Ledovskoy A, Li H, Neu C, Sinthuprasith T, Wang Y, Wolfe E, Xia F, Harr R, Karchin PE, Poudyal N, Sturdy J, Thapa P, 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, Ruggles T, Savin A, Smith N, Smith WH, Taylor D, Woods N
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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.
Bartenschlager R, Baumert TF, Bukh J, Houghton M, Lemon SM, Lindenbach BD, Lohmann V, Moradpour D, Pietschmann T, Rice CM, Thimme R, Wakita T
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Critical challenges and emerging opportunities in hepatitis C virus research in an era of potent antiviral therapy: Considerations for scientists and funding agencies
VIRUS RESEARCH 2018 MAR 15; 248(?):53-62
The development and clinical implementation of direct-acting antivirals (DAAs) has revolutionized the treatment of chronic hepatitis C. Infection with any hepatitis C virus (HCV) genotype can now be eliminated in more than 95% of patients with short courses of all-oral, well-tolerated drugs, even in those with advanced liver disease and liver transplant recipients. DAAs have proven so successful that some now consider HCV amenable to eradication, and continued research on the virus of little remaining medical relevance. However, given 400,000 HCV-related deaths annually important challenges remain, including identifying those who are infected, providing access to treatment and reducing its costs. Moreover, HCV infection rarely induces sterilizing immunity, and those who have been cured with DAAs remain at risk for reinfection. Thus, it is very unlikely that global eradication and elimination of the cancer risk associated with HCV infection can be achieved without a vaccine, yet research in that direction receives little attention. Further, over the past two decades HCV research has spearheaded numerous fundamental discoveries in the fields of molecular and cell biology, immunology and microbiology. It will continue to do so, given the unique opportunities afforded by the reagents and knowledge base that have been generated in the development and clinical application of DAAs. Considering these critical challenges and new opportunities, we conclude that funding for HCV research must be sustained.
Levran O, Peles E, Randesi M, da Rosa JC, Shen PH, Rotrosen J, Adelson M, Kreek MJ
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Genetic variations in genes of the stress response pathway are associated with prolonged abstinence from heroin
PHARMACOGENOMICS 2018 MAR; 19(4):333-341
Aim: This study assesses whether genetic variants in stress-related genes are associated with prolonged abstinence from heroin in subjects that are not in long-term methadone treatment. Methods: Frequencies of 117 polymorphisms in 30 genes were compared between subjects with history of heroin addiction, either without agonist treatment (n = 129) or in methadone maintenance treatment (n = 923). Results: SNP rs1500 downstream of CRHBP and an interaction of SNPs rs10482672 (NR3C1) and rs4234955 (NPY1R/NPY5R) were significantly associated with prolonged abstinence without agonist treatment. Conclusion: This study suggests that variability in stress-related genes may contribute to the ability of certain subjects to remain in prolonged abstinence from heroin, possibly due to higher resilience to stress.
Macdougall CE, Wood EG, Loschko J, Scagliotti V, Cassidy FC, Robinson ME, Feldhahn N, Castellano L, Voisin MB, Marelli-Berg F, Gaston-Massuet C, Charalambous M, Longhi MP
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Visceral Adipose Tissue Immune Homeostasis Is Regulated by the Crosstalk between Adipocytes and Dendritic Cell Subsets
CELL METABOLISM 2018 MAR 6; 27(3):588-601.e4
Visceral adipose tissue (VAT) has multiple roles in orchestrating whole-body energy homeostasis. In addition, VAT is now considered an immune site harboring an array of innate and adaptive immune cells with a direct role in immune surveillance and host defense. We report that conventional dendritic cells (cDCs) in VAT acquire a tolerogenic phenotype through upregulation of pathways involved in adipocyte differentiation. While activation of the Wnt/beta-catenin pathway in cDC1 DCs induces IL-10 production, upregulation of the PPAR gamma pathway in cDC2 DCs directly suppresses their activation. Combined, they promote an anti-inflammatory milieu in vivo delaying the onset of obesity-induced chronic inflammation and insulin resistance. Under long-term over-nutrition, changes in adipocyte biology curtail beta-catenin and PPARg activation, contributing to VAT inflammation.
Schachter J, Martel J, Lin CS, Chang CJ, Wu TR, Lu CC, Ko YF, Lai HC, Ojcius DM, Young JD
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Effects of obesity on depression: A role for inflammation and the gut microbiota
BRAIN BEHAVIOR AND IMMUNITY 2018 MAR; 69(?):1-8
Depression is a mental disorder associated with environmental, genetic and psychological factors. Recent studies indicate that chronic neuro-inflammation may affect brain physiology and alter mood and behavior. Consumption of a high-fat diet leads to obesity and chronic systemic inflammation. The gut micro biota mediates many effects of a high-fat diet on human physiology and may also influence the mood and behavior of the host. We review here recent studies suggesting the existence of a link between obesity, the gut microbiota and depression, focusing on the mechanisms underlying the effects of a high-fat diet on chronic inflammation and brain physiology. This body of research suggests that modulating the composition of the gut microbiota using prebiotics and probiotics may produce beneficial effects on anxiety and depression. (C) 2017 Elsevier Inc. All rights reserved.
Adam RC, Yang H, Ge YJ, Lien WH, Wang P, Zhao YL, Polak L, Levorse J, Baksh SC, Zheng DY, Fuchs E
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Temporal Layering of Signaling Effectors Drives Chromatin Remodeling during Hair Follicle Stem Cell Lineage Progression
CELL STEM CELL 2018 MAR 1; 22(3):398-413.e7
Tissue regeneration relies on resident stem cells (SCs), whose activity and lineage choices are influenced by the microenvironment. Exploiting the synchronized, cyclical bouts of tissue regeneration in hair follicles (HFs), we investigate how microenvironment dynamics shape the emergence of stemcell lineages. Employing epigenetic and ChIP-seq profiling, we uncover how signal-dependent transcription factors couple spatiotemporal cues to chromatin dynamics, thereby choreographing stem cell lineages. Using enhancer-driven reporters, mutagenesis, and genetics, we show that simultaneous BMP-inhibitory and WNT signals set the stage for lineage choices by establishing chromatin platforms permissive for diversification. Mechanistically, when binding of BMP effector pSMAD1 is relieved, enhancers driving HF-stemcellmaster regulators are silenced. Concomitantly, multipotent, lineage-fated enhancers silent in HF-stem cells become activated by exchanging WNT effectors TCF3/4 for LEF1. Throughout regeneration, lineage enhancers continue reliance upon LEF1 but then achieve specificity by accommodating additional incoming signaling effectors. Barriers to progenitor plasticity increase when diverse, signal-sensitive transcription factors shape LEF1-regulated enhancer dynamics.
McGarvey R, Dowling N, Cohen JE
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Two Processes Regulating Trophic Energy Flow in Pelagic and Terrestrial Ecosystems: Trophic Efficiency and Body Size-Dependent Biomass Production (A Reply to Giacomini)
AMERICAN NATURALIST 2018 MAR; 191(3):364-367
We proposed two hypotheses to explain why food chains are longer in pelagic than terrestrial ecosystems: greater trophic efficiency of pelagic animal taxa at lower trophic levels and a higher pelagic biomass production rate at lower trophic levels because of smaller pelagic body masses. Giacomini favored the former, invoking in support the energetic equivalence hypothesis. We reply that the energetic equivalence hypothesis does not describe populations at differing trophic levels and so does not refute a significant role for body-mass dependence in explaining faster trophic transfer in pelagic ecosystems. Metabolic scaling as body mass to the exponent 1/4, widely accepted, remains important for trophic dynamic models. We suggest a likelihood method to compare the two hypotheses on the basis of models of whole-ecosystem energetics.
Waltari E, Jia MX, Jiang CS, Lu H, Huang J, Fernandez C, Finzi A, Kaufmann DE, Markowitz M, Tsuji M, Wu XL
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5 ' Rapid Amplification of cDNA Ends and Illumina MiSeq Reveals B Cell Receptor Features in Healthy Adults, Adults With Chronic HIV-1 Infection, Cord Blood, and Humanized Mice
FRONTIERS IN IMMUNOLOGY 2018 MAR 26; 9(?):? Article 628
Using 5' rapid amplification of cDNA ends, Illumina MiSeq, and basic flow cytometry, we systematically analyzed the expressed B cell receptor (BCR) repertoire in 14 healthy adult PBMCs, 5 HIV-1+adult PBMCs, 5 cord blood samples, and 3 HIS-CD4/B mice, examining the full-length variable region of mu, gamma, alpha, kappa, and lambda chains for V-gene usage, somatic hypermutation (SHM), and CDR3 length. Adding to the known repertoire of healthy adults, Illumina MiSeq consistently detected small fractions of reads with high mutation frequencies including hypermutated mu reads, and reads with long CDR3s. Additionally, the less studied IgA repertoire displayed similar characteristics to that of IgG. Compared to healthy adults, the five HIV-1 chronically infected adults displayed elevated mutation frequencies for all mu, gamma, alpha, kappa, and lambda chains examined and slightly longer CDR3 lengths for gamma, alpha, and lambda. To evaluate the reconstituted human BCR sequences in a humanized mouse model, we analyzed cord blood and HIS-CD4/B mice, which all lacked the typical SHM seen in the adult reference. Furthermore, MiSeq revealed identical unmutated IgM sequences derived from separate cell aliquots, thus for the first time demonstrating rare clonal members of unmutated IgM B cells by sequencing.