944 research outputs found

    DNA synthesis determines the binding mode of the human mitochondrial single-stranded DNA-binding protein

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    [EN] Single-stranded DNA-binding proteins (SSBs) play a key role in genome maintenance, binding and organizing single-stranded DNA (ssDNA) intermediates. Multimeric SSBs, such as the human mitochondrial SSB (HmtSSB), present multiple sites to interact with ssDNA, which has been shown in vitro to enable them to bind a variable number of single-stranded nucleotides depending on the salt and protein concentration. It has long been suggested that different binding modes might be used selectively for different functions. To study this possibility, we used optical tweezers to determine and compare the structure and energetics of long, individual HmtSSB¿DNA complexes assembled on preformed ssDNA and on ssDNA generated gradually during `in situ¿ DNA synthesis. We show that HmtSSB binds to preformed ss-DNA in two major modes, depending on salt and protein concentration. However, when protein binding was coupled to strand-displacement DNA synthesis, only one of the two binding modes was observed under all experimental conditions. Our results reveal a key role for the gradual generation of ssDNA in modulating the binding mode of a multimeric SSB protein and consequently, in generating the appropriate nucleoprotein structure for DNA synthetic reactions required for genome maintenance.We are grateful to Prof. M. Salas laboratory (CBMSO-CSIC) for generously providing the Phi29 DNA polymerase and to Juan P. García Villaluenga (UCM) for useful discussions. Spanish Ministry of Economy and Competitiveness [MAT2015-71806-R to J.R.A-G, FIS2010-17440, FIS2015-67765-R to F.J.C., BFU2012-31825, BFU2015-63714-R to B.I.]; Spanish Ministry of Education, Culture and Sport [FPU13/02934 to J.J., FPU13/02826 to E.B-H.]; National Institutes of Health [GM45925 to L.S.K.]; University of Tampere (to G.L.C.); Programa de Financiacion Universidad Complutense de Madrid-Santander Universidades [CT45/15-CT46/15 to F.C.]. Funding for open access charge: Spanish Ministry of Economy and Competitiveness [BFU2015-63714-R].Morin, J.; Cerrón, F.; Jarillo, J.; Beltran-Heredia, E.; Ciesielski, G.; Arias-Gonzalez, JR.; Kaguni, L.... (2017). DNA synthesis determines the binding mode of the human mitochondrial single-stranded DNA-binding protein. Nucleic Acids Research. 45(12):7237-7248. https://doi.org/10.1093/nar/gkx395S723772484512Shereda, R. D., Kozlov, A. G., Lohman, T. M., Cox, M. M., & Keck, J. L. (2008). 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    Upregulation of NKG2D ligands impairs hematopoietic stem cell function in Fanconi anemia

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    Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Next Generation EU; EUROFANCOLEN); Comunidad de Madrid (AvanCell, B2017/BMD-3692); ICREA-Academia program.Fanconi anemia (FA) is the most prevalent inherited bone marrow failure (BMF) syndrome. Nevertheless, the pathophysiological mechanisms of BMF in FA have not been fully elucidated. Since FA cells are defective in DNA repair, we hypothesized that FA hematopoietic stem and progenitor cells (HSPCs) might express DNA damage-associated stress molecules such as natural killer group 2 member D ligands (NKG2D-Ls). These ligands could then interact with the activating NKG2D receptor expressed in cytotoxic NK or CD8+ T cells, which may result in progressive HSPC depletion. Our results indeed demonstrated upregulated levels of NKG2D-Ls in cultured FA fibroblasts and T cells, and these levels were further exacerbated by mitomycin C or formaldehyde. Notably, a high proportion of BM CD34+ HSPCs from patients with FA also expressed increased levels of NKG2D-Ls, which correlated inversely with the percentage of CD34+ cells in BM. Remarkably, the reduced clonogenic potential characteristic of FA HSPCs was improved by blocking NKG2D-NKG2D-L interactions. Moreover, the in vivo blockage of these interactions in a BMF FA mouse model ameliorated the anemia in these animals. Our study demonstrates the involvement of NKG2D-NKG2D-L interactions in FA HSPC functionality, suggesting an unexpected role of the immune system in the progressive BMF that is characteristic of FA

    radon progeny recoil effect in retrospective indoor glass dosimetry

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    Radon gas diffusion and progeny transport in air, are mechanisms to be considered in retrospective glass dosimetry. With the aim to contribute to the understanding of the Rn progeny recoil energy role in this dosimetry methodology, we carried out a simulation employing GEANT4 code. In that, we assumed the chemical compound of the glass that is used commonly in households. Results are compared to experimentally measured 210Bi concentration to show that the recoil energy helps the progenies incrustation, mainly for the 218,214Po alpha emitters but do not influence bismuth-210 diffusion directly. A significant difference exists between our results and measured values; that is interpreted as due to atomic displacement by primary knock-on atoms. The SiO2 molecule binding energy breaks and the following ion recombination, induce a structural modification between the atom by e.g. cavities formation in such a way that reduces significantly the radon progeny diffusion speed

    Measurement of the photon+b+b-jet production differential cross section in ppˉp\bar{p} collisions at \sqrt{s}=1.96~\TeV

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    We present measurements of the differential cross section dsigma/dpT_gamma for the inclusive production of a photon in association with a b-quark jet for photons with rapidities |y_gamma|< 1.0 and 30<pT_gamma <300 GeV, as well as for photons with 1.5<|y_gamma|< 2.5 and 30< pT_gamma <200 GeV, where pT_gamma is the photon transverse momentum. The b-quark jets are required to have pT>15 GeV and rapidity |y_jet| < 1.5. The results are based on data corresponding to an integrated luminosity of 8.7 fb^-1, recorded with the D0 detector at the Fermilab Tevatron ppˉp\bar{p} Collider at sqrt(s)=1.96 TeV. The measured cross sections are compared with next-to-leading order perturbative QCD calculations using different sets of parton distribution functions as well as to predictions based on the kT-factorization QCD approach, and those from the Sherpa and Pythia Monte Carlo event generators.Comment: 10 pages, 9 figures, submitted to Phys. Lett.

    Limits on anomalous trilinear gauge boson couplings from WW, WZ and Wgamma production in pp-bar collisions at sqrt{s}=1.96 TeV

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    We present final searches of the anomalous gammaWW and ZWW trilinear gauge boson couplings from WW and WZ production using lepton plus dijet final states and a combination with results from Wgamma, WW, and WZ production with leptonic final states. The analyzed data correspond to up to 8.6/fb of integrated luminosity collected by the D0 detector in pp-bar collisions at sqrt{s}=1.96 TeV. We set the most stringent limits at a hadron collider to date assuming two different relations between the anomalous coupling parameters Delta\kappa_\gamma, lambda, and Delta g_1^Z for a cutoff energy scale Lambda=2 TeV. The combined 68% C.L. limits are -0.057<Delta\kappa_\gamma<0.154, -0.015<lambda<0.028, and -0.008<Delta g_1^Z<0.054 for the LEP parameterization, and -0.007<Delta\kappa<0.081 and -0.017<lambda<0.028 for the equal couplings parameterization. We also present the most stringent limits of the W boson magnetic dipole and electric quadrupole moments.Comment: 10 pages, 5 figures, submitted to PL

    Search for single top quarks in the tau+jets channel using 4.8 fb1^{-1} of ppˉp\bar{p} collision data

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    We present the first direct search for single top quark production using tau leptons. The search is based on 4.8 fb1^{-1} of integrated luminosity collected in ppˉp\bar{p} collisions at s\sqrt{s}=1.96 TeV with the D0 detector at the Fermilab Tevatron Collider. We select events with a final state including an isolated tau lepton, missing transverse energy, two or three jets, one or two of them bb tagged. We use a multivariate technique to discriminate signal from background. The number of events observed in data in this final state is consistent with the signal plus background expectation. We set in the tau+jets channel an upper limit on the single top quark cross section of \TauLimObs pb at the 95% C.L. This measurement allows a gain of 4% in expected sensitivity for the observation of single top production when combining it with electron+jets and muon+jets channels already published by the D0 collaboration with 2.3 fb1^{-1} of data. We measure a combined cross section of \SuperCombineXSall pb, which is the most precise measurement to date.Comment: 12 pages, 5 figure

    b-Jet Identification in the D0 Experiment

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    Algorithms distinguishing jets originating from b quarks from other jet flavors are important tools in the physics program of the D0 experiment at the Fermilab Tevatron p-pbar collider. This article describes the methods that have been used to identify b-quark jets, exploiting in particular the long lifetimes of b-flavored hadrons, and the calibration of the performance of these algorithms based on collider data.Comment: submitted to Nuclear Instruments and Methods in Physics Research

    Measurement of the dijet invariant mass cross section in proton anti-proton collisions at sqrt{s} = 1.96 TeV

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    The inclusive dijet production double differential cross section as a function of the dijet invariant mass and of the largest absolute rapidity of the two jets with the largest transverse momentum in an event is measured in proton anti-proton collisions at sqrt{s} = 1.96 TeV using 0.7 fb^{-1} integrated luminosity collected with the D0 detector at the Fermilab Tevatron Collider. The measurement is performed in six rapidity regions up to a maximum rapidity of 2.4. Next-to-leading order perturbative QCD predictions are found to be in agreement with the data.Comment: Published in Phys. Lett. B, 693, (2010), 531-538, 8 pages, 2 figures, 6 table
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