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Culyba MJ, Kubiak JM, Mo CY, Goulian M, Kohli RM
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Non-equilibrium repressor binding kinetics link DNA damage dose to transcriptional timing within the SOS gene network

PLOS GENETICS 2018 JUN; 14(6):? Article e1007405
Biochemical pathways are often genetically encoded as simple transcription regulation networks, where one transcription factor regulates the expression of multiple genes in a pathway. The relative timing of each promoter's activation and shut-off within the network can impact physiology. In the DNA damage repair pathway (known as the SOS response) of Escherichia coli, approximately 40 genes are regulated by the LexA repressor. After a DNA damaging event, LexA degradation triggers SOS gene transcription, which is temporally separated into subsets of 'early', 'middle', and 'late' genes. Although this feature plays an important role in regulating the SOS response, both the range of this separation and its underlying mechanism are not experimentally defined. Here we show that, at low doses of DNA damage, the timing of promoter activities is not separated. Instead, timing differences only emerge at higher levels of DNA damage and increase as a function of DNA damage dose. To understand mechanism, we derived a series of synthetic SOS gene promoters which vary in LexA-operator binding kinetics, but are otherwise identical, and then studied their activity over a large dose-range of DNA damage. In distinction to established models based on rapid equilibrium assumptions, the data best fit a kinetic model of repressor occupancy at promoters, where the drop in cellular LexA levels associated with higher doses of DNA damage leads to non-equilibrium binding kinetics of LexA at operators. Operators with slow LexA binding kinetics achieve their minimal occupancy state at later times than operators with fast binding kinetics, resulting in a time separation of peak promoter activity between genes. These data provide insight into this remarkable feature of the SOS pathway by demonstrating how a single transcription factor can be employed to control the relative timing of each gene's transcription as a function of stimulus dose.
Abramowicz H, Abt I, Adamczyk L, Adamus M, Aggarwal R, Andreev V, Antonelli S, Aushev V, Baghdasaryan A, Begzsuren K, Behnke O, Behrens U, Belousov A, Bertolin A, Bloch I, Bolz A, Boudry V, Brandt G, Brisson V, Britzger D, Brock I, Brook NH, Brugnera R, Bruni A, Buniatyan A, Bussey PJ, Bylinkin A, Bystritskaya L, Caldwell A, Campbell AJ, Avila KBC, Capua M, Catterall CD, Cerny K, Chekelian V, Chwastowski J, Ciborowski J, Ciesielski R, Contreras JG, Cooper-Sarkar AM, Corradi M, Cvach J, Dainton JB, Daum K, Dementiev RK, Devenish RCE, Diaconu C, Dobre M, Dusini S, Eckerlin G, Egli S, Elsen E, Favart L, Fedotov A, Feltesse J, Fleischer M, Fomenko A, Foster B, Gallo E, Garfagnini A, Gayler J, Geiser A, Gizhko A, Gladilin LK, Goerlich L, Gogitidze N, Golubkov YA, Gouzevitch M, Grab C, Grebenyuk A, Greenshaw T, Grindhammer G, Grzelak G, Gwenlan C, Haidt D, Henderson RCW, Hladky J, Hlushchenko O, Hochman D, Hoffmann D, Horisberger R, Hreus T, Huber F, Ibrahim ZA, Iga Y, Jacquet M, Janssen X, Jomhari NZ, Jung AW, Jung H, Kadenko I, Kananov S, Kapichine M, Karshon U, Katzy J, Kaur P, Kiesling C, Kisielewska D, Klanner R, Klein M, Klein U, Kleinwort C, Kogler R, Korzhavina IA, Kostka P, Kotanski A, Kovalchuk N, Kowalski H, Kretzschmar J, Krucker D, Kruger K, Krupa B, Kuprash O, Kuze M, Landon MPJ, Lange W, Laycock P, Lebedev A, Levchenko BB, Levonian S, Levy A, Libov V, Lipka K, Lisovyi M, List B, List J, Lobodzinski B, Lohr B, Lohrmann E, Longhin A, Lukina OY, Makarenko I, Malinovski E, Malka J, Martyn HU, Masciocchi S, Maxfield SJ, Mehta A, Meyer AB, Meyer H, Meyer J, Mikocki S, Idris FM, Nasir NM, Morozov A, Muller K, Myronenko V, Nagano K, Nam JD, Naumann T, Newman PR, Nicassio M, Niebuhr C, Nowak G, Olsson JE, Onderwaater J, Onishchuk Y, Ozerov D, Pascaud C, Patel GD, Paul E, Perez E, Perlanski W, Petrukhin A, Picuric I, Pirumov H, Pitzl D, Pokrovskiy NS, Polifka R, Polini A, Przybycien M, Radescu V, Raicevic N, Ravdandorj T, Reimer P, Rizvi E, Robmann P, Roosen R, Rostovtsev A, Rotaru M, Ruspa M, Salek D, Sankey DPC, Sauter M, Sauvan E, Saxon DH, Schioppa M, Schmitt S, Schneekloth U, Schoeffel L, Schoning A, Schorner-Sadenius T, Sefkow F, Selyuzhenkov I, Shcheglova LM, Shushkevich S, Shyrma Y, Skillicorn IO, Slominski W, Solano A, Soloviev Y, Sopicki P, South D, Spaskov V, Specka A, Stanco L, Steder M, Stefaniuk N, Stella B, Stern A, Stopa P, Straumann U, Surrow B, Sykora T, Sztuk-Dambietz J, Tassi E, Thompson PD, Tokushuku K, Tomaszewska J, Traynor D, Truol P, Tsakov I, Tseepeldorj B, Tsurugai T, Turcato M, Turkot O, Tymieniecka T, Valkarova A, Vallee C, Van Mechelen P, Vazdik Y, Verbytskyi A, Abdullah WATW, Wegener D, Wichmann K, Wing M, Wunsch E, Yamada S, Yamazaki Y, Zacek J, Zarnecki AF, Zawiejski L, Zenaiev O, Zhang Z, Zhautykov BO, Zlebcik R, Zohrabyan H, Zomer F
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Combination and QCD analysis of charm and beauty production cross-section measurements in deep inelastic ep scattering at HERA

EUROPEAN PHYSICAL JOURNAL C 2018 JUN 9; 78(6):? Article 473
Measurements of open charm and beauty production cross sections in deep inelastic ep scattering at HERA from the H1 and ZEUS Collaborations are combined. Reduced cross sections are obtained in the kinematic range of negative four-momentum transfer squared of the photon 2.5 GeV2 <= Q(2) <= 2000 GeV2 and Bjorken scaling variable 3 . 10(-5) <= x(Bj) <= 5 . 10(-2). The combination method accounts for the correlations of the statistical and systematic uncertainties among the different datasets. Perturbative QCD calculations are compared to the combined data. A next-to-leading order QCD analysis is performed using these data together with the combined inclusive deep inelastic scattering cross sections from HERA. The running charmand beauty-quark masses are determined as m(c)(m(c)) = 1.290(-0.041)(+0.046)(exp/fit)(-0.014)(+0.062)(model)(0.031)(+0.003)(par ameterisation) GeV and m(b)(m(b)) = 4.049(-0.109)(+0.104)(exp/fit)(-0.032)(+0.090)(model)(-0.031)(+0.001)(pa rameterisation) GeV.
Zhang YX, Danner OS, Nakadai T, Fayzikhodjaeva G, Lu YH, Lazar MA, Roeder RG, Friedman JM
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A noncanonical PPAR gamma/RXR alpha-binding sequence regulates leptin expression in response to changes in adipose tissue mass

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2018 JUN 26; 115(26):E6039-E6047
Leptin expression decreases after fat loss and is increased when obesity develops, and its proper quantitative regulation is essential for the homeostatic control of fat mass. We previously reported that a distant leptin enhancer 1 (LE1), 16 kb upstream from the transcription start site (TSS), confers fat-specific expression in a bacterial artificial chromosome transgenic (BACTG) reporter mouse. However, this and the other elements that we identified do not account for the quantitative changes in leptin expression that accompany alterations of adipose mass. In this report, we used an assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) to identify a 17-bp noncanonical peroxisome proliferator-activated receptor gamma (PPAR gamma)/retinoid X receptor alpha (RXR alpha)-binding site, leptin regulatory element 1 (LepRE1), within LE1, and show that it is necessary for the fat-regulated quantitative control of reporter (luciferase) expression. While BACTG reporter mice with mutations in this sequence still show fat-specific expression, luciferase is no longer decreased after food restriction and weight loss. Similarly, the increased expression of leptin reporter associated with obesity in oWob mice is impaired. A functionally analogous LepRE1 site is also found in a second, redundant DNA regulatory element 13 kb downstream of the TSS. These data uncouple the mechanisms conferring qualitative and quantitative expression of the leptin gene and further suggest that factor(s) that bind to LepRE1 quantitatively control leptin expression and might be components of a lipid-sensing system in adipocytes.
Erdos M
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Neonatal screening of severe combined immunodeficiencies

ORVOSI HETILAP 2018 JUN; 159(23):948-956
Severe combined immunodeficiency is the first immune deficiency disorder which was included in the newborn screening program in the United States in 2010. In Hungary, newborn screening for severe combined immunodeficiencies is crucial because of the routine BCG vaccination, as in the case of an affected newborn with negative family history, the vaccine may lead to fatal BCG-itis. This paper analyzes the possibilities of introducing newborn screening for severe combined immunodeficiencies and summarizes current experiences and results.
Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, Brandstetter J, Brondolin E, Dragicevic M, Ero J, Del Valle AE, Flechl M, Friedl M, Fruhwirth R, Ghete VM, Grossmann J, Hrubec J, Jeitler M, Konig A, Krammer N, Kratschmer I, Liko D, Madlener T, Mikulec I, Pree E, Rad N, Rohringer H, Schieck J, Schofbeck R, Spanring M, Spitzbart D, Taurok A, Waltenberger W, Wittmann J, Wulzi CE, Zarucki M, Chekhovsky V, Mossolov V, Gonzalez JS, De Wolf EA, Di Croce D, Janssen X, Lauwers J, Pieters M, De Klundert MV, 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, Bilin B, Brun H, Clerbaux B, De Lentdecker G, Delannoy H, Dorney B, Fasanella G, Favart L, Goldouzian R, Grebenyuk A, Kalsi AK, Lenzi T, Luetic J, Maerschalk T, Seva T, Starling E, Vander Velde C, Vanlaer P, Vannerom D, Yonamine R, Zenoni F, Cornelis T, Dobur D, Fagot A, Gul M, Khvastunov I, Poyraz D, Roskas C, Trocino D, Tytgat M, Verbeke W, Vit M, 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, Krintiras G, Lemaitre V, Magitteri A, Mertens A, Musich M, Piotrzkowski K, Quertenmont L, Saggio A, Marono MV, Wertz S, Zobec J, Alda WL, Alves FL, Alves GA, Brito L, Silva GC, 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 LM, Malbouisson H, De Almeida MM, Herrera CM, Mundim L, Nogima H, Rosas LJS, Santoro A, Sznajder A, Thiel M, Manganote EJ, De Araujo FTD, Pereira AV, Ahuja S, Bernardes CA, Tomei TRP, Gregores EM, Mercadante PC, Novaes SF, Padula SS, Abad DR, Vargas JCR, Aleksandrov A, Hadjiiska R, Iaydjiev P, Marinov A, 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, Zhao J, Ban Y, Chen G, Li J, Li Q, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Wang Y, 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, Abdalla H, Abdelalim AA, Khalill S, Bhowmik S, Dewanjee RK, Kadastik M, Perrini L, Raidal M, 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, Maenpaa T, Siikonen H, Tuominen E, Tuominiemi 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, 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, Charlot C, de Cassagnac RG, Jo M, Kucher I, Lisniak S, Lobanov A, Blanco JM, Nguyen M, Ochando C, Ortona G, Paganini P, Pigard P, Salerno R, Sauvan JB, Sirois Y, Leiton AGS, Yilmaz Y, Zabi A, Zghiche A, Agram JL, Andrea J, Bloch D, Brom JM, Buttignol M, Chabert EC, Collard C, Conte E, Coubez X, Drouhin F, Fontaine JC, Gele D, Goerlach U, Jansova M, Juillot P, Le Bihan AC, Tonon N, Van Hove P, Gadrat S, Beauceron S, Bernet C, Boudoul G, Chanon N, 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, Lattaud H, Lethuillier M, Mirabito L, Pequegnot AL, Perries S, Popov A, Sordini V, Vander Donckt M, Viret S, Zhang S, Khvedelidze A, Lomidze D, Autermann C, Feld L, Kiesel MK, Klein K, Lipinski M, Preuten M, Schomakers C, Schulz J, Teroerde M, Wittmer B, Zhukov V, Albert A, Duchardt D, Endres M, Erdmann M, Erdweg S, Esch T, Fischer R, Guth A, 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, Kunsken A, Muller T, Nehrkorn A, Nowack A, Pistone C, Pooth ., 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, De Wit A, 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, Lipka K, Lohmann W, Mankel R, Melzer-Pellmann IA, Meyer AB, Meyer M, Missiroli M, Mittag G, Mnich J, Mussgiller A, Pitzl D, Raspereza A, Savitskyi M, Saxena P, Shevchenko R, Stefaniuk N, Tholen H, Van Onsem GP, Walsh R, Wen Y, Wichmann K, Wissing C, Zenaiev O, Aggleton R, Bein S, Blobel V, Vignali MC, Dreyer T, Garutti E, Gonzalez D, Haller J, Hinzmann A, Hoffmann M, Karavdina A, Kasieczka G, Klanner R, Kogler R, Kovalchuk N, Kurz S, Marconi D, Multhaup J, Niedziela M, Nowatschin D, Peiffer T, Perieanu A, Reimers A, Scharf C, Schleper P, Schmidt A, Schumann S, Schwandt J, Sonneveld J, Stadie H, Steinbruck G, Stober FM, Stover M, Troendle D, Usai E, Vanhoefer A, Vormwald B, Akbiyik M, Barth C, Baselga M, Baur S, Butz E, Caspart R, Chwalek T, Colombo F, De Boer W, Dierlamm A, Faltermann N, Freund B, Friese R, Giffels M, Har-Rendorf MA, 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, Kyriakis A, Loukas D, Topsis-Giotis I, Karathanasis G, Kesisoglou S, Panagiotou A, Saoulidou N, Tziaferi E, Kousouris K, Papakrivopoulos I, Evangelou I, Foudas C, Gianneios P, Katsoulis P, Kokkas P, Mallios S, Manthos N, Papadopoulos I, Paradas E, Strologas J, Triantis FA, Tsitsonis D, Csanad M, Filipovic N, Pasztor G, Suranyi O, Veres GI, Bencze G, Hajdu C, Horvath D, Hunyadi A, Sikler F, Veszpremi V, Vesztergombi G, Vami TA, 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, Mal P, Mandal K, Nayak A, Sahoo DK, Sahoo N, Swain SK, Bansal S, Beri SB, Bhatnagar V, Chawla R, Dhingra N, Gupta R, Kaur A, Kaur M, Kaur S, Kumar R, Kumari P, Mehta A, Sharma S, Singh JB, Walia G, Kumar A, Shah A, Bhardwaj A, Chauhan S, Choudhary BC, Garg RB, Keshri S, Kumar A, Malhotra S, Naimuddin M, Ranjan K, Sharma R, Bhardwaj R, Bhattacharya R, Bhattacharya S, Bhawandeep U, Bhowmik D, Dey S, Dutt S, Dutta S, Ghosh S, Majumdar N, Modak A, Mondal K, Mukhopadhyay S, Nandan S, Purohit A, Rout PK, Roy A, Chowdhury SR, Sarkar S, Sharan M, Singh B, Thakur S, Behera PK, Chudasama R, Dutta D, Jha V, Kumar V, Mohanty AK, Netrakanti PK, Pant LM, Shukla P, Topkar A, Aziz T, Dugad S, Mahakud B, Mitra S, Mohanty GB, Sur N, Sutar B, Banerjee S, Bhattacharya S, Chatterjee S, Das P, Guchait M, Jain S, Kumar S, Maity M, Majumder G, Mazumdar K, Sarkar T, Wickramage N, Chauhan S, Dube S, Hegde V, Kapoor A, Kothekar K, Pandey S, Rane A, Sharma S, Chenarani S, Tadavani EE, Etesami SM, Khakzad M, Najafabadi MM, Naseri M, Mehdiabadi SP, Hosseinabadi FR, Safarzadeh B, Zeinali M, Felcini M, Grunewald M, Abbrescia M, Calabria C, Colaleo A, Creanzaa D, Cristella L, Filippis N, Palma M, Florio A, Errico F, Fiore L, Iaselli G, Lezki S, Maggi G, Magzi M, Marangelli B, Miniello G, My S, Nuzzo S, Pompili A, Pugliese G, Radogna R, Ranieri A, Selvaggi G, Sharma A, Silvestris L, Venditti R, Verwilligen P, Zito G, Abbiendi G, Battilana C, Bonacorsi D, Borgonovi L, Braibant-Giacomelli S, Brigliadori L, 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, Guiduccia L, Iemmi F, Marcellini S, Masetti G, Montanari A, Navarria FL, Perrotta A, Rovelli T, Siroli GP, Tosi N, Albergo S, Costa S, Mattia A, Giordano F, Potenza R, Tricomi A, Tuve C, Barbagli G, Chatterjee K, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Latino G, 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, Ravera F, Robutti E, Tosi S, Benaglia A, Beschi A, Brianza L, Brivio F, Ciriolo V, Dinardo ME, Fiorendi S, Gennai S, Ghezzi A, Govoni P, Malberti M, Malvezzi S, Manzoni RA, Menasce D, Moroni L, Paganoni M, Pauwels K, Pedrini D, Pigazzini S, Ragazzi S, Fatis TT, Buontempo S, Cavallo N, Guida S, Fabozzi F, Fienga F, Iorio AOM, Khan WA, Lista L, Meola S, Paolucci P, Sciacca C, Thyssen F, Azzi P, Bacchetta N, Benatoa L, Biasotto M, Bisello D, Boletti A, Carlin R, Oliveira ACA, Checchia P, Dall'Osso M, Manzano PDC, Dorigo T, Dosselli U, Gasparini F, Gozzelino A, Lacaprara S, Lujan P, Margoni M, Meneguzzo AT, Pozzobon N, Ronchese P, Rossin R, Simonetto F, Tiko A, Torassa E, Zanetti M, Zotto P, Braghieri A, Magnani A, Montagna P, Ratti SP, Re V, Ressegotti M, Riccardi C, Salvini P, Vai I, Vitulo P, Solestizi LA, Biasini M, Bilei GM, 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, Bianchini L, 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, Messineo A, Palla F, Rizzi A, Spagnolo P, Tenchini R, Tonelli G, Venturi A, Verdini PG, Barone L, Cavallari F, Cipriani M, Daci N, Re D, Marco E, Diemoz M, Gelli S, Longo E, Margaroli F, Marzocchi B, Meridiani P, Organtini G, Paramatti R, Preiato F, Rahatlou S, Rovelli C, Santanastasio F, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Bartosik N, Bellan R, Biino C, Cartiglia N, Castello R, Cenna F, Costa M, Covarelli R, Degano A, Demari 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, Romero A, Ruspa M, Sacchi R, Shchelina K, Sola V, Solano A, Staiano A, Traczyk P, Belforte S, Casarsa M, Cossutti F, 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, 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, Kim H, Kim JH, Lee JSH, Park IC, Choi Y, Hwang C, Lee J, Yu I, Dudenas V, Juodagalvis A, Vaitkus J, Ahmed I, Ibrahim ZA, Ali MABM, Idris FM, Abdullah WATW, Yusli MN, Zolkapli Z, Reyes-Almanza R, Ramirez-Sanchez G, Duran-Osuna MC, Castilla-Valdez H, De La Cruz-Burelo E, La Cruz ID, Rabadan-Trejo RI, Lopez-Fernandez R, Guisao JM, Sanchez-Hernandez A, Moreno SC, Barrera CO, Valencia FV, Eysermans J, Pedraza I, Ibarguen HAS, Estrada CU, Pineda AM, Krofcheck D, Bheesette S, Butler PH, Ahmad A, Ahmad M, Hassan Q, Hoorani HR, Saddique A, Shah MA, Shoaib M, Waqas M, Bialkowska H, Bluj M, Boimska B, Frueboes T, Gorski M, Kazana M, Nawrocki K, Szleper M, Zalewski P, Bunkowski K, Byszuk A, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Olszewski M, Pyskir A, Walczak M, Bargassa P, Silva CBDE, Di Francesco A, Faccioli P, Galinhas B, Gallinaro M, Hollar J, Leonardo N, Iglesias LL, Nemallapudi MV, Seixas J, Strong G, Toldaiev ., Vadruccio D, Varela J, Afanasiev S, Bunin P, Gavrilenko M, Golutvin I, 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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, 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, Akchurin N, Damgov J, De Guio F, Dudero PR, Faulkner J, Gurpinar E, Kunori S, Lamichhane K, Lee SW, 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, Carlsmith D, Dasu S, Dodd L, Duric S, Comber B, Grothe M, Herndon M, Herve A, Hussain U, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Rekovic V, Ruggles T, Savin A, Smith N, Smith WH, Woods N
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Measurements of differential cross sections of top quark pair production as a function of kinematic event variables in proton-proton collisions at root s=13 TeV

JOURNAL OF HIGH ENERGY PHYSICS 2018 JUN 1; ?(6):? Article 002
Measurements of differential t (t) over bar production cross sections are presented in the single-lepton decay channel, as a function of a number of kinematic event variables. The measurements are performed with proton-proton collision data at root s = 13 TeV, collected by the CMS experiment at the LHC during 2016, with an integrated luminosity of 35.9 fb(-1). The data are compared to a variety of state-of-the-art leading-order and next-to-leading order t (t) over bar simulations.
Tromp AT, Van Gent M, Abrial P, Martin A, Jansen JP, De Haas CJC, Van Kessel KPM, Bardoel BW, Kruse E, Bourdonnay E, Boettcher M, McManus MT, Day CJ, Jennings MP, Lina G, Vandenesch F, Van Strijp JAG, Lebbink RJ, Haas PJA, Henry T, Spaan AN
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Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin

NATURE MICROBIOLOGY 2018 JUN; 3(6):708-717
The staphylococcal bi-component leukocidins Panton-Valentine leukocidin (PVL) and gamma-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins' S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1(KI)) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1(KI) mice. Compared to humans, murine hC5aR1(KI) neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin's F-component LukF-PV. By performing a genome-wide CRISPR-Cas9 screen, we identified CD45 as a receptor for LukF-PV. The human-specific interaction between LukF-PV and CD45 provides a molecular explanation for resistance of hC5aR1(KI) mouse neutrophils to PVL and probably contributes to the lack of a PVL-mediated phenotype during infection in these mice. This study demonstrates an unsuspected role of the F-component in driving the sensitivity of human phagocytes to PVL.
Skocek O, Nobauer T, Weilguny L, Traub FM, Xia CYN, Molodtsov MI, Grama A, Yamagata M, Aharoni D, Cox DD, Golshani P, Vaziri A
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High-speed volumetric imaging of neuronal activity in freely moving rodents

NATURE METHODS 2018 JUN; 15(6):429-432
Thus far, optical recording of neuronal activity in freely behaving animals has been limited to a thin axial range. We present a head-mounted miniaturized light-field microscope (MiniLFM) capable of capturing neuronal network activity within a volume of 700 x 600 x 360 mu m(3) at 16 Hz in the hippocampus of freely moving mice. We demonstrate that neurons separated by as little as similar to 15 mu m and at depths up to 360 mu m can be discriminated.
Mak ACY, White MJ, Eckalbar WL, Szpiech ZA, Oh SS, Pino-Yanes M, Hu DL, Goddard P, Huntsman S, Galanter J, Wu AC, Himes BE, Germer S, Vogel JM, Bunting KL, Eng C, Salazar S, Keys KL, Liberto J, Nuckton TJ, Nguyen TA, Torgerson DG, Kwok PY, Levin AM, Celedon JC, Forno E, Hakonarson H, Sleiman PM, Dahlin A, Tantisira KG, Weiss ST, Serebrisky D, Brigino-Buenaventura E, Farber HJ, Meade K, Lenoir MA, Avila PC, Sen S, Thyne SM, Rodriguez-Cintron W, Winkler CA, Moreno-Estrada A, Sandoval K, Rodriguez-Santana JR, Kumar R, Williams LK, Ahituv N, Ziv E, Seibold MA, Darnell RB, Zaitlen N, Hernandez RD, Burchard EG
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Whole-Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2018 JUN 15; 197(12):1552-1564
Rationale: Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response. Objectives: To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children. Methods: We performed the first whole-genome sequencing pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR. Measurements and Main Results: We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P < 3.53 X 10(-7)) and suggestive (P < 7.06 X 10(-6)) loci near genes previously associated with lung capacity (DNAH5), immunity (NFKB1 and PLCB1), and beta-adrenergic signaling (ADAMTS3 and COX18). Functional analyses of the BDR-associated SNP in NFKB1 revealed potential regulatory function in bronchial smooth muscle cells. The SNP is also an expression quantitative trait locus for a neighboring gene, SLC39A8. The lack of other asthma study populations with BDR and whole-genome sequencing data on minority children makes it impossible to perform replication of our rare variant associations. Minority underrepresentation also poses significant challenges to identify age-matched and population-matched cohorts of sufficient sample size for replication of our common variant findings. Conclusions: The lack of minority data, despite a collaboration of eight universities and 13 individual laboratories, highlights the urgent need for a dedicated national effort to prioritize diversity in research. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations.
Galea S, Vaughan RD
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On Looking Ahead to Mitigate Threats to Population Health: A Public Health of Consequence, June 2018

AMERICAN JOURNAL OF PUBLIC HEALTH 2018 JUN; 108(6):722-723
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Measurement of b hadron lifetimes in pp collisions at root s=8TeV

EUROPEAN PHYSICAL JOURNAL C 2018 JUN 7; 78(6):? Article 457
Measurements are presented of the lifetimes of the B-0, B-s(0), Lambda(0)(b), and B-c(+) hadrons using the decay channels B-0 -> J/psi K*(892)(0), B-0 -> J/psi K-S(0), B-s(0) -> J/psi pi(+)pi(-), B-s(0) -> J/psi phi(1020), Lambda(0)(b) -> J/psi Lambda(0), and B-c(+) -> J/psi pi(+). The data sample, corresponding to an integrated luminosity of 19.7 fb(-1), was collected by the CMS detector at the LHC in proton-proton collisions at root s = 8TeV. The B-0 life-time is measured to be 453.0 +/- 1.6 (stat) +/- 1.8 (syst) mu m in J/psi K*(892)(0) and 457.8 +/- 2.7 (stat) +/- 2.8 (syst) mu m in J/psi K-S(0), which results in a combined measurement of c tau(0) = 454.1 +/- 1.4 (stat) +/- 1.7 (syst) mu m. The effective lifetime of the B-s(0) meson is measured in two decay modes, with contributions from different amounts of the heavy and light eigenstates. This results in two different measured lifetimes: c tau(0)(Bs) -> J/psi pi(+)pi(-) = 502.7 +/- 10.2 (stat) +/- 3.4 (syst) mu m and c tau(0)(Bs) -> J/psi phi(1020) = 443.9 +/- 2.0 (stat) +/- 1.5 (syst) mu m. The Lambda(0)(b) lifetime is found to be 442.9 +/- 8.2 (stat) +/- 2.8 (syst) mu m. The precision from each of these channels is as good as or better than previous measurements. The B-c(+) lifetime, measured with respect to the B+ to reduce the systematic uncertainty, is 162.3 +/- 7.8 (stat) +/- 4.2 (syst) +/- 0.1 (tau(B+)) mu m. All results are in agreement with current world-average values.