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Bick MJ, Malik S, Mustaev A, Darst SA
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TFIIB Is Only similar to 9 angstrom Away from the 5 '-End of a Trimeric RNA Primer in a Functional RNA Polymerase II Preinitiation Complex

PLOS ONE 2015 MAR 16; 10(3):? Article e0119007
Recent X-ray crystallographic studies of Pol II in complex with the general transcription factor (GTF) IIB have begun to provide insights into the mechanism of transcription initiation. These structures have also shed light on the architecture of the transcription preinitiation complex (PIC). However, structural characterization of a functional PIC is still lacking, and even the topological arrangement of the GTFs in the Pol II complex is a matter of contention. We have extended our activity-based affinity crosslinking studies, initially developed to investigate the interaction of bacterial RNA polymerase with s, to the eukaryotic transcription machinery. Towards that end, we sought to identify GTFs that are within the Pol II active site in a functioning PIC. We provide biochemical evidence that TFIIB is located within similar to 9 angstrom of the -2 site of promoter DNA, where it is positioned to play a role in de novo transcription initiation.
Luo P, Yu XZ, Wang WG, Fan SL, Li XC, Wang JW
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Crystal structure of a phosphorylation-coupled vitamin C transporter

NATURE STRUCTURAL & MOLECULAR BIOLOGY 2015 MAR; 22(3):238-241
Bacteria use vitamin C (L-ascorbic acid) as a carbon source under anaerobic conditions. The phosphoenolpyruvate-dependent phosphotransferase system (PTS), comprising a transporter (UlaA), a IIB-like enzyme (UlaB) and a IIA-like enzyme (UlaC), is required for the anaerobic uptake of vitamin C and its phosphorylation to L-ascorbate 6-phosphate. Here, we present the crystal structures of vitamin C-bound UlaA from Escherichia coil in two conformations at 1.65-angstrom and 2.35-angstrom resolution. UlaA forms a homodimer and exhibits a new fold. Each UlaA protomer consists of 11 transmembrane segments arranged into a 'V-motif' domain and a 'core' domain. The V motifs form the interface between the two protomers, and the core-domain residues coordinate vitamin C. The alternating access of the substrate from the opposite side of the cell membrane may be achieved through rigid-body rotation of the core relative to the V motif.
Anchan R, Gerami-Naini B, Lindsey JS, Ho JWK, Kiezun A, Lipskind S, Ng N, LiCausi JA, Kim CS, Brezina P, Tuschl T, Maas R, Kearns WG, Williams Z
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Efficient Differentiation of Steroidogenic and Germ-Like Cells from Epigenetically-Related iPSCs Derived from Ovarian Granulosa Cells

PLOS ONE 2015 MAR 9; 10(3):?
To explore restoration of ovarian function using epigenetically-related, induced pluripotent stem cells (iPSCs), we functionally evaluated the epigenetic memory of novel iPSC lines, derived from mouse and human ovarian granulosa cells (GCs) using c-Myc, Klf4, Sox2 and Oct4 retroviral vectors. The stem cell identity of the mouse and human GC-derived iPSCs (mGriPSCs, hGriPSCs) was verified by demonstrating embryonic stem cell (ESC) antigen expression using immunocytochemistry and RT-PCR analysis, as well as formation of embryoid bodies (EBs) and teratomas that are capable of differentiating into cells from all three germ layers. GriPSCs' gene expression profiles associate more closely with those of ESCs than of the originating GCs as demonstrated by genome-wide analysis of mRNA and microRNA. A comparative analysis of EBs generated from three different mouse cell lines (mGriPSCs; fibroblast-derived iPSC, mFiPSCs; G4 embryonic stem cells, G4 mESCs) revealed that differentiated mGriPSC-EBs synthesize 10-fold more estradiol (E2) than either differentiated FiPSC- or mESC-EBs under identical culture conditions. By contrast, mESC-EBs primarily synthesize progesterone (P4) and FiPSC-EBs produce neither E2 nor P4. Differentiated mGriPSC-EBs also express ovarian markers (AMHR, FSHR, Cyp19a1, ER and Inha) as well as markers of early gametogenesis (Mvh, Dazl, Gdf9, Boule and Zp1) more frequently than EBs of the other cell lines. These results provide evidence of preferential homotypic differentiation of mGriPSCs into ovarian cell types. Collectively, our data support the hypothesis that generating iPSCs from the desired tissue type may prove advantageous due to the iPSCs' epigenetic memory.
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Mirman N, Kaufman GN, Patterson JR, Ryd A, Salvati E, Skinnari L, Sun W, Teo WD, Thom J, Thompson J, Tucker J, Weng Y, Winstrom L, Wittich P, Winn D, Abdullin S, Albrow M, Anderson J, Apollinari G, Bauerdick LAT, Beretvas A, Berryhill J, Bhat PC, Burkett K, Butler JN, Cheung HWK, Chlebana F, Cihangir S, Elvira VD, Fisk I, Freeman J, Gao Y, Gottschalk E, Gray L, Green D, Grunendahl S, Gutsche O, Hanlon J, Hare D, Harris RM, Hirschauer J, Hooberman B, Jindariani S, Johnson M, Joshi U, Kaadze K, Klima B, Kreis B, Kwan S, Linacre J, Lincoln D, Lipton R, Liu T, Lykken J, Maeshima K, Marraffino JM, Outschoorn VIM, Maruyama S, Mason D, McBride P, Mishra K, Mrenna S, Musienko Y, Nahn S, Newman-Holmes C, O'Dell V, Prokofyev O, Sexton-Kennedy E, Sharma S, Soha A, Spalding WJ, Spiegel L, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vidal R, Whitbeck A, Whitmore J, Yang F, Acosta D, Avery P, Bourilkov D, Carver M, Cheng T, Curry D, Das S, De Gruttola M, Di Giovanni GP, Field RD, Fisher 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Malek M, Murray M, Noonan D, Sanders S, Sekaric J, Stringer R, Wang Q, Wood JS, Barfuss AF, Chakaberia I, Ivanov A, Khalil S, Makouski M, Maravin Y, Saini LK, Shrestha S, Skhirtladze N, Svintradze I, Gronberg J, Lange D, Rebassoo F, Wright D, Baden A, Belloni A, Calvert B, Eno SC, Gomez JA, Hadley NJ, Kellogg RG, Kolberg T, Lu Y, Marionneau M, Mignerey AC, Pedro K, Skuja A, Tonjes MB, Tonwar SC, Apyan A, Barbieri R, Bauer G, Busza W, Cali IA, Chan M, Di Matteo L, Dutta V, Ceballos GG, Goncharov M, Gulhan D, Klute M, Lai YS, Lee YJ, Levin A, Luckey PD, Ma T, Paus C, Ralph D, Roland C, Roland G, Stephans GSF, Stockli F, Sumorok K, Velicanu D, Veverka J, Wyslouch B, Yang M, Zanetti M, Zhukova V, Dahmes B, Gude A, Kao SC, Klapoetke K, Kubota Y, Mans J, Pastika N, Rusack R, Singovsky A, Tambe N, Turkewitz J, Acosta JG, Oliveros S, Avdeeva E, Bloom K, Bose S, Claes DR, Dominguez A, Suarez RG, Keller J, Knowlton D, Kravchenko I, Lazo-Flores J, Malik S, Meier F, Snow GR, Dolen J, Godshalk A, 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P, Miller DH, Neumeister N, Radburn-Smith BC, Shi X, Shipsey I, Silvers D, Svyatkovskiy A, Wang F, Xie W, Xu L, Yoo HD, Zablocki J, Zheng Y, Parashar N, Stupak J, Adair A, Akgun B, Ecklund KM, Geurts FJM, Li W, Michlin B, Padley BP, Redjimi R, Roberts J, Zabel J, Betchart B, Bodek A, Covarelli R, de Barbaro P, Demina R, Eshaq Y, Ferbel T, Garcia-Bellido A, Goldenzweig P, Han J, Harel A, Khukhunaishvili A, Petrillo G, Vishnevskiy D, Ciesielski R, Demortier L, Goulianos K, Lungu G, Mesropian C, Arora S, Barker A, Chou JP, Contreras-Campana C, Contreras-Campana E, Duggan D, Ferencek D, Gershtein Y, Gray R, Halkiadakis E, Hidas D, Lath A, Panwalkar S, Park M, Patel R, Salur S, Schnetzer S, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Rose K, Spanier S, York A, Bouhali O, Eusebi R, Flanagan W, Gilmore J, Kamon T, Khotilovich V, Krutelyov V, Montalvo R, Osipenkov I, Pakhotin Y, Perloff A, Roe J, Rose A, Safonov A, Sakuma T, Suarez I, Tatarinov A, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero PR, Faulkner J, Kovitanggoon K, Kunori S, Lee SW, Libeiro T, Volobouev I, Appelt E, Delannoy AG, Greene S, Gurrola A, Johns W, Maguire C, Mao Y, Melo A, Sharma M, Sheldon P, Snook B, Tuo S, Velkovska J, Arenton MW, Boutle S, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Lin C, Neu C, Wood J, Clarke C, Harr R, Karchin PE, Don CKK, Lamichhane P, Sturdy J, Belknap DA, Carlsmith D, Cepeda M, Dasu S, Dodd L, Duric S, Friis E, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Lanaro A, Lazaridis C, Levine A, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ross I, Sarangi T, Savin A, Smith WH, Vuosalo C, Woods N
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Measurements of jet multiplicity and differential production cross sections of Z plus jets events in proton-proton collisions at root s=7 TeV

PHYSICAL REVIEW D 2015 MAR 11; 91(5):? Article 052008
Measurements of differential cross sections are presented for the production of a Z boson and at least one hadronic jet in proton-proton collisions at root s = 7 TeV, recorded by the CMS detector, using a data sample corresponding to an integrated luminosity of 4.9 fb(-1). The jet multiplicity distribution is measured for up to six jets. The differential cross sections are measured as a function of jet transverse momentum and pseudorapidity for the four highest transverse momentum jets. The distribution of the scalar sum of jet transverse momenta is also measured as a function of the jet multiplicity. The measurements are compared with theoretical predictions at leading and next-to-leading order in perturbative QCD.
Yao Y, Norris EH, Strickland S
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The cellular origin of laminin determines its role in blood pressure regulation

CELLULAR AND MOLECULAR LIFE SCIENCES 2015 MAR; 72(5):999-1008
Laminin of different cellular sources has distinct functions. In addition to vascular smooth muscle cells (SMCs), aorta also contains a small population of nestin(+) cells, whose function remains unknown. This study investigates the role of SMC- and nestin(+) cell-derived laminin in blood pressure (BP) regulation and SMC contractibility. Using mice with laminin deficiency in SMCs (SKO) or nestin(+) cells (NKO), we examined laminin-dependent changes in BP. Contractile protein expression was reduced in SKO but not NKO mice, consistent with their, respectively, low and normal baseline BP measurements. At the ultrastructural level, SKO SMCs maintained the contractile phenotype with reduced elasticity, whereas NKO SMCs switched to the synthetic phenotype and showed degeneration. Additionally, angiotensin II (Ang II) significantly increased BP in SKO but not NKO mice. It also enhanced contractile proteins to the same levels and induced SMC degeneration in both knockout mice. These data suggest that SMC laminin regulates BP via modulating contractile protein expression, whereas nestin(+) cell-derived laminin contributes to SMC phenotypic switch.
Deglincerti A, Brivanlou AH
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The generation of sex cells

CELL RESEARCH 2015 MAR; 25(3):267-268
Primordial germ cells (PGCs) are the earliest population of germ cells established during embryonic development and constitute the beginning of the totipotent state. A recent study provides a new protocol for the efficient generation of PGC-like cells from human embryonic stem cells, providing an in vitro platform to study human PGC differentiation and specification.
Boisson-Dupuis S, Bustamante J, El-Baghdadi J, Camcioglu Y, Parvaneh N, El Azbaoui S, Agader A, Hassani A, El Hafidi N, Mrani NA, Jouhadi Z, Ailal F, Najib J, Reisli I, Zamani A, Yosunkaya S, Gulle-Girit S, Yildiran A, Cipe FE, Torun SH, Metin A, Atikan BY, Hatipoglu N, Aydogmus C, Kilic SS, Dogu F, Karaca N, Aksu G, Kutukculer N, Keser-Emiroglu M, Somer A, Tanir G, Aytekin C, Adimi P, Mahdaviani SA, Mamishi S, Bousfiha A, Sanal O, Mansouri D, Casanova JL, Abel L
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Inherited and acquired immunodeficiencies underlying tuberculosis in childhood

IMMUNOLOGICAL REVIEWS 2015 MAR; 264(1):103-120
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN- immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey.
Lee J, Breton G, Oliveira TYK, Zhou YJ, Aljoufi A, Puhr S, Cameron MJ, Sekaly RP, Nussenzweig MC, Liu K
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Restricted dendritic cell and monocyte progenitors in human cord blood and bone marrow

JOURNAL OF EXPERIMENTAL MEDICINE 2015 MAR; 212(3):385-399
In mice, two restricted dendritic cell (DC) progenitors, macrophage/dendritic progenitors (MDPs) and common dendritic progenitors (CDPs), demonstrate increasing commitment to the DC lineage, as they sequentially lose granulocyte and monocyte potential, respectively. Identifying these progenitors has enabled us to understand the role of DCs and monocytes in immunity and tolerance in mice. In humans, however, restricted monocyte and DC progenitors remain unknown. Progress in studying human DC development has been hampered by lack of an in vitro culture system that recapitulates in vivo DC hematopoiesis. Here we report a culture system that supports development of CD34(+) hematopoietic stem cell progenitors into the three major human DC subsets, monocytes, granulocytes, and NK and B cells. Using this culture system, we defined the pathway for human DC development and revealed the sequential origin of human DCs from increasingly restricted progenitors: a human granulocyte-monocyte-DC progenitor (hGMDP) that develops into a human monocyte-dendritic progenitor (hMDP), which in turn develops into monocytes, and a human CDP (hCDP) that is restricted to produce the three major DC subsets. The phenotype of the DC progenitors partially overlaps with granulocyte-macrophage progenitors (GMPs). These progenitors reside in human cord blood and bone marrow but not in the blood or lymphoid tissues.
Chatrchyan S, Khachatryan V, Sirunyan AM, Adam W, Bergauer T, Dragicevic M, Ero J, Fabjan C, Friedl M, Fruhwirth R, Ghete VM, Hartl C, Hormann N, Hrubec J, Jeitler M, Kiesenhofer W, Knunz V, Krammer M, Kratschmer I, Liko D, Mikulec I, Rabady D, Rahbaran B, Rohringer H, Schofbeck R, Strauss J, Taurok A, Treberer-Treberspurg W, Waltenberger W, Wulz CE, Mossolov V, Shumeiko N, Gonzalez JS, Alderweireldt S, Bansal M, Bansal S, Cornelis T, De Wolf EA, Janssen X, Knutsson A, Luyckx S, Ochesanu S, Roland B, Rougny R, Van De Klundert M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Van Spilbeeck A, Blekman F, Blyweert S, D'Hondt J, Daci N, Heracleous N, Keaveney J, Lowette S, Maes M, Olbrechts A, Python Q, Strom D, Tavernier S, Van Doninck W, Van Mulders P, Van Onsem GP, Villella I, Caillol C, Clerbaux B, De Lentdecker G, Dobur D, Favart L, Gay APR, Grebenyuk A, Leonard A, Mohammadi A, Pernie L, Reis T, Seva T, Thomas L, Vander Velde C, Vanlaer P, Wang J, Adler V, Beernaert K, Benucci L, Cimmino A, Costantini S, Crucy S, Dildick S, Fagot A, Garcia G, Mccartin J, Rios AAO, Ryckbosch D, Diblen SS, Sigamani M, Strobbe N, Thyssen F, Tytgat M, Yazgan E, Zaganidis N, Basegmez S, Beluffi C, Bruno G, Castello R, Caudron A, Ceard L, Da Silveira GG, Delaere C, du Pree T, Favart D, Forthomme L, Giammanco A, Hollar J, Jez P, Komm M, Lemaitre V, Nuttens C, Pagano D, Perrini L, Pin A, Piotrzkowski K, Popov A, Quertenmont L, Selvaggi M, Marono MV, Garcia JMV, Beliy N, Caebergs T, Daubie E, Hammad GH, Alda WL, Alves GA, Brito L, Martins MC, Pol ME, Carvalho W, Chinellato J, Custodio A, Da Costa EM, Damiao DD, Martins CD, De Souza SF, Malbouisson H, Figueiredo DM, Mundim L, Nogima H, Da Silva WLP, Santaolalla J, Santoro A, Sznajder A, Manganote EJT, Pereira AV, Bernardes CA, Tomei TRFP, Gregores EM, Mercadante PG, Novaes SF, Padula SS, Aleksandrov A, Genchev V, Iaydjiev P, Marinov A, Piperov S, Rodozov M, Sultanov G, Vutova M, Dimitrov A, Glushkov I, Hadjiiska R, Kozhuharov V, Litov L, 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E, Delannoy AG, Greene S, Gurrola A, Johns W, Maguire C, Mao Y, Melo A, Sharma M, Sheldon P, Snook B, Tuo S, Velkovska J, Arenton MW, Boutle S, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Lin C, Neu C, Wood J, Harr R, Karchin PE, Don CKK, Lamichhane P, Sturdy J, Belknap DA, Carlsmith D, Cepeda M, Dasu S, Duric S, Friis E, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Lanaro A, Lazaridis C, Levine A, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ross I, Sarangi T, Savin A, Smith WH, Woods N
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Study of Z production in PbPb and pp collisions at root s(NN)=2.76 TeV in the dimuon and dielectron decay channels

JOURNAL OF HIGH ENERGY PHYSICS 2015 MAR 4; ?(3):? Article 022
The production of Z bosons is studied in the dimuon and dielectron decay channels in PbPb and pp collisions at root s(NN) = 2.76TeV, using data collected by the CMS experiment at the LHC. The PbPb data sample corresponds to an integrated luminosity of about 166 mu b(-1), while the pp data sample collected in 2013 at the same nucleon-nucleon centre-of-mass energy has an integrated luminosity of 5.4 pb(-1). The Z boson yield is measured as a function of rapidity, transverse momentum, and collision centrality. The ratio of PbPb to pp yields, scaled by the number of inelastic nucleon-nucleon collisions, is found to be 1.06 +/- 0.05 (stat) +/- 0.08 (syst) in the dimuon channel and 1.02 +/- 0.08 (stat) +/- 0.15 (syst) in the dielectron channel, for centrality-integrated Z boson production. This binary collision scaling is seen to hold in the entire kinematic region studied, as expected for a colourless probe that is unaffected by the hot and dense QCD medium produced in heavy ion collisions.
Zhang XQ, Bogunovic D, Payelle-Brogard B, Francois-Newton V, Speer SD, Yuan C, Volpi S, Li Z, Sanal O, Mansouri D, Tezcan I, Rice GI, Chen CY, Mansouri N, Mahdaviani SA, Itan Y, Boisson B, Okada S, Zeng L, Wang X, Jiang H, Liu WQ, Han TT, Liu DL, Ma T, Wang B, Liu MG, Liu JY, Wang QK, Yalnizoglu D, Radoshevich L, Uze G, Gros P, Rozenberg F, Zhang SY, Jouanguy E, Bustamante J, Garcia-Sastre A, Abel L, Lebon P, Notarangelo LD, Crow YJ, Boisson-Dupuis S, Casanova JL, Pellegrini S
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Human intracellular ISG15 prevents interferon-alpha/beta over-amplification and auto-inflammation (vol 517, pg 89. 2015)

NATURE 2015 MAR 19; 519(7543):?