190 research outputs found

    A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries

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    Neural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impair neuronal differentiation and migration. Kinases of the protein kinase C (PKC) family mediate the release of growth factors that participate in different steps of the neurogenic process, particularly, novel PKC isozymes facilitate the release of the neurogenic growth factor neuregulin. We have demonstrated herein that a plant derived diterpene, (EOF2; CAS number 2230806-06-9), with the capacity to activate PKC facilitates the release of neuregulin 1, and promotes neuroblasts differentiation and survival in cultures of subventricular zone (SVZ) isolated cells in a novel PKC dependent manner. Local infusion of this compound in mechanical cortical injuries induces neuroblast enrichment within the perilesional area, and noninvasive intranasal administration of EOF2 promotes migration of neuroblasts from the SVZ towards the injury, allowing their survival and differentiation into mature neurons, being some of them cholinergic and GABAergic. Our results elucidate the mechanism of EOF2 promoting neurogenesis in injuries and highlight the role of novel PKC isozymes as targets in brain injury regeneration

    A Measurement of Rb using a Double Tagging Method

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    The fraction of Z to bbbar events in hadronic Z decays has been measured by the OPAL experiment using the data collected at LEP between 1992 and 1995. The Z to bbbar decays were tagged using displaced secondary vertices, and high momentum electrons and muons. Systematic uncertainties were reduced by measuring the b-tagging efficiency using a double tagging technique. Efficiency correlations between opposite hemispheres of an event are small, and are well understood through comparisons between real and simulated data samples. A value of Rb = 0.2178 +- 0.0011 +- 0.0013 was obtained, where the first error is statistical and the second systematic. The uncertainty on Rc, the fraction of Z to ccbar events in hadronic Z decays, is not included in the errors. The dependence on Rc is Delta(Rb)/Rb = -0.056*Delta(Rc)/Rc where Delta(Rc) is the deviation of Rc from the value 0.172 predicted by the Standard Model. The result for Rb agrees with the value of 0.2155 +- 0.0003 predicted by the Standard Model.Comment: 42 pages, LaTeX, 14 eps figures included, submitted to European Physical Journal

    Measurement of the B+ and B-0 lifetimes and search for CP(T) violation using reconstructed secondary vertices

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    The lifetimes of the B+ and B-0 mesons, and their ratio, have been measured in the OPAL experiment using 2.4 million hadronic Z(0) decays recorded at LEP. Z(0) --> b (b) over bar decays were tagged using displaced secondary vertices and high momentum electrons and muons. The lifetimes were then measured using well-reconstructed charged and neutral secondary vertices selected in this tagged data sample. The results aretau(B+) = 1.643 +/- 0.037 +/- 0.025 pstau(Bo) = 1.523 +/- 0.057 +/- 0.053 pstau(B+)/tau(Bo) = 1.079 +/- 0.064 +/- 0.041,where in each case the first error is statistical and the second systematic.A larger data sample of 3.1 million hadronic Z(o) decays has been used to search for CP and CPT violating effects by comparison of inclusive b and (b) over bar hadron decays, No evidence fur such effects is seen. The CP violation parameter Re(epsilon(B)) is measured to be Re(epsilon(B)) = 0.001 +/- 0.014 +/- 0.003and the fractional difference between b and (b) over bar hadron lifetimes is measured to(Delta tau/tau)(b) = tau(b hadron) - tau((b) over bar hadron)/tau(average) = -0.001 +/- 0.012 +/- 0.008

    ADAM15 mediates upregulation of Claudin-1 expression in breast cancer cells

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    A Disintegrin and Metalloproteinase-15 (ADAM15) is a transmembrane protein involved in protein ectodomain shedding, cell adhesion and signalling. We previously cloned and characterised alternatively spliced variants of ADAM15 that differ in their intracellular domains and demonstrated correlation of the expression of specific variants with breast cancer prognosis. In this study we have created isogenic cell panels (MDA-MB-231 and MCF-7) expressing five ADAM15 variants including wildtype and catalytically inactive forms. The expression of ADAM15 isoforms in MDA-MB-231 cells led to cell clustering to varying degree, without changes in EMT markers vimentin, slug and E-cadherin. Analysis of tight junction molecules revealed ADAM15 isoform specific, catalytic function dependent upregulation of Claudin-1. The expression of ADAM15A, and to a lesser degree of C and E isoforms led to an increase in Claudin-1 expression in MDA-MB-231 cells, while ADAM15B had no effect. In MCF-7 cells, ADAM15E was the principal variant inducing Claudin-1 expression. Sh-RNA mediated down-regulation of ADAM15 in ADAM15 over-expressing cells reduced Claudin-1 levels. Additionally, downregulation of endogenous ADAM15 expression in T47D cells by shRNA reduced endogenous Claudin-1 expression confirming a role for ADAM15 in regulating Claudin-1 expression. The PI3K/Akt/mTOR pathway was involved in regulating Claudin-1 expression downstream of ADAM15. Immunofluorescence analysis of MDA-MB-231 ADAM15A expressing cells showed Claudin-1 at cell-cell junctions, in the cytoplasm and nuclei. ADAM15 co-localised with Claudin-1 and ZO1 at cell-cell junctions. Immunoprecipitation analysis demonstrated complex formation between ADAM15 and ZO1/ZO2. These findings highlight the importance of ADAM15 Intra Cellular Domain-mediated interactions in regulating substrate selection and breast cancer cell phenotype

    Study of hadronic event-shape variables in multijet final states in pp collisions at √s=7 TeV

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    Constraints on parton distribution functions and extraction of the strong coupling constant from the inclusive jet cross section in pp collisions at √s=7 TeV

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    Peer reviewe

    Experimental properties of gluon and quark jets from a point source

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    Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data.Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data.Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data.Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data
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