HDAC6 Regulates LPS-Tolerance in Astrocytes

Inflammatory tolerance is a crucial mechanism that limits inflammatory responses in order to avoid prolonged inflammation that may damage the host. Evidence that chronic inflammation contributes to the neuropathology of prevalent neurodegenerative and psychiatric diseases suggests that inflammatory tolerance mechanisms are often inadequate to control detrimental inflammation in the central nervous system. Thus, identifying mechanisms that regulate neuroinflammatory tolerance may reveal opportunities for bolstering tolerance to reduce chronic inflammation in these diseases. Examination of tolerance after repeated lipopolysaccharide (LPS) treatment of mouse primary astrocytes demonstrated that histone deacetylase (HDAC) activity promoted tolerance, opposite to the action of glycogen synthase kinase-3 (GSK3), which counteracts tolerance. HDAC6 in particular was found to be critical for tolerance induction, as its deacetylation of acetyl-tubulin was increased during LPS tolerance, this was enhanced by inhibition of GSK3, and the HDAC6 inhibitor tubacin completely blocked tolerance and the promotion of tolerance by inhibition of GSK3. These results reveal opposing interactions between HDAC6 and GSK3 in regulating tolerance, and indicate that shifting the balance between these two opposing forces on inflammatory tolerance can obliterate or enhance tolerance to LPS in astrocytes

Search for neutral MSSM Higgs bosons decaying to a pair of tau leptons in pp collisions

Peer reviewe

Measurement of top quark–antiquark pair production in association with a W or Z boson in pp collisions at √s=8 TeV

Peer reviewe

Measurement of prompt J/ψ pair production in pp collisions at √s = 7 Tev

Peer reviewe

Searches for electroweak production of charginos, neutralinos, and sleptons decaying to leptons and W, Z, and Higgs bosons in pp collisions at 8 TeV

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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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Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Search for B → μ μ And B0 → μ+ μ- Decays

A search for the rare decays B → μ μ and B → μ μ is performed in pp collisions at ps = 7TeV, with a data sample corresponding to an integrated luminosity of 5 fb collected by the CMS experiment at the LHC. In both decays, the number of events observed after all selection requirements is consistent with the expectation from background plus standard model signal predictions. The resulting upper limits on the branching fractions are B(B → μ μ-) < 7:7 × 10 and B(B → μ μ ) < 1:8 × 10 at 95% confidence level

Evidence for the 125 GeV Higgs boson decaying to a pair of tau leptons

A search for a standard model Higgs boson decaying into a pair of tau leptons is performed using events recorded by the CMS experiment at the LHC in 2011 and 2012. The dataset corresponds to an integrated luminosity of 4.9 fb(-1) at a centre-of-mass energy of 7 TeV and 19.7 fb(-1) at 8 TeV. Each tau lepton decays hadronically or leptonically to an electron or a muon, leading to six different final states for the tau-lepton pair, all considered in this analysis. An excess of events is observed over the expected background contributions, with a local significance larger than 3 standard deviations for m (H) values between 115 and 130 GeV. The best fit of the observed H -> tau tau signal cross section times branching fraction for m(H) = 125 GeV is 0.78 +/- 0.27 times the standard model expectation. These observations constitute evidence for the 125 GeV Higgs boson decaying to a pair of tau leptons