866 research outputs found

    Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease

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    Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. However, its molecular pathogenesis is incompletely characterized and clinical biomarkers remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of early, diet-related, liver injury and to assess novel candidate biomarkers in NAFLD patients. Methods: Liver membrane and cytosolic protein fractions from high fat fed apolipoprotein E knockout (ApoE−/−) animals were analyzed by quantitative proteomics, utilizing isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential protein expression was confirmed independently by immunoblotting and immunohistochemistry in both murine tissue and biopsies from paediatric NAFLD patients. Candidate biomarkers were analyzed by enzyme-linked immunosorbent assay in serum from adult NAFLD patients. Results: Through proteomic profiling, we identified decreased expression of hepatic glyoxalase 1 (GLO1) in a murine model. GLO1 protein expression was also found altered in tissue biopsies from paediatric NAFLD patients. In vitro experiments demonstrated that, in response to lipid loading in hepatocytes, GLO1 is first hyperacetylated then ubiquitinated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 59 biopsy-confirmed adult NAFLD patients, increased serum levels of the primary methylglyoxal-derived advanced glycation endproduct, hydroimidazolone (MG-H1) were significantly correlated with body mass index (r = 0.520, p < 0.0001). Conclusion: Collectively these results demonstrate the dysregulation of GLO1 in NAFLD and implicate the acetylation-ubquitination degradation pathway as the functional mechanism. Further investigation of the role of GLO1 in the molecular pathogenesis of NAFLD is warranted. Keywords: Non-alcoholic fatty liver disease, Glyoxalase, Methylglyoxal, Proteomics, iTRA

    Update on the Direct Detection of Supersymmetric Dark Matter

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    We compare updated predictions for the elastic scattering of supersymmetric neutralino dark matter with the improved experimental upper limit recently published by CDMS II. We take into account the possibility that the \pi-nucleon \Sigma term may be somewhat larger than was previously considered plausible, as may be supported by the masses of exotic baryons reported recently. We also incorporate the new central value of m_t, which affects indirectly constraints on the supersymmetric parameter space, for example via calculations of the relic density. Even if a large value of \Sigma is assumed, the CDMS II data currently exclude only small parts of the parameter space in the constrained MSSM (CMSSM) with universal soft supersymmetry-breaking Higgs, squark and slepton masses. None of the previously-proposed CMSSM benchmark scenarios is excluded for any value of \Sigma, and the CDMS II data do not impinge on the domains of the CMSSM parameter space favoured at the 90 % confidence level in a recent likelihood analysis. However, some models with non-universal Higgs, squark and slepton masses and neutralino masses \lappeq 700 GeV are excluded by the CDMS II data.Comment: 25 pages, 28 eps figure

    Neutralino Dark Matter Elastic Scattering in a Flat and Accelerating Universe

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    In SUGRA inspired supersymmetric models with universal boundary conditions for the soft masses, the scalar cross section σscalar\sigma_{scalar} for the elastic neutralino--nucleon scattering is in general several orders of magnitude below the sensitivity of current experiments. For large tanβ\tan \beta and low M1/2,m0M_{1/2}, m_0 values, the theoretically predicted σscalar\sigma_{scalar} can approach the sensitivity of these experiments (106pb\approx 10^{-6} pb) being at the same time in agreement with recent cosmological data, which impose severe restrictions on the CDM relic density, and with accelerator experiments which put lower bounds on sparticle and Higgs boson masses. Further improvement of the sensitivity of DAMA and CDMS experiments will probe the large tanβ\tan \beta region of the parameter space in the vicinity of the boundaries of the parameter space allowed by chargino and Higgs searches.Comment: 15 pages, 9 figures. A note added; version to appear in MPL

    Partial wave treatment of Supersymmetric Dark Matter in the presence of CP - violation

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    We present an improved partial wave analysis of the dominant LSP annihilation channel to a fermion-antifermion pair which avoids the non-relativistic expansion being therefore applicable near thresholds and poles. The method we develop allows of contributions of any partial wave in the total angular momentum J in contrast to partial wave analyses in terms of the orbital angular momentum L of the initial state, which is usually truncated to p-waves, and yields very accurate results. The method is formulated in such a way as to allow easy handling of CP-violating phases residing in supersymmetric parameters. We apply this refined partial wave technique in order to calculate the neutralino relic density in the constrained MSSM (CMSSM) in the presence of CP-violating terms occurring in the Higgs - mixing parameter \mu and trilinear A coupling for large tanb. The inclusion of CP-violating phases in mu and A does not upset significantly the picture and the annihilation of the LSP's to a b b_bar, through Higgs exchange, is still the dominant mechanism in obtaining cosmologically acceptable neutralino relic densities in regions far from the stau-coannihilation and the `focus point'. Significant changes can occur if we allow for phases in the gaugino masses and in particular the gluino mass.Comment: 23 pages LaTeX, 10 eps figures, version to appear in PR

    Neutrino Fluxes from CMSSM LSP Annihilations in the Sun

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    We evaluate the neutrino fluxes to be expected from neutralino LSP annihilations inside the Sun, within the minimal supersymmetric extension of the Standard Model with supersymmetry-breaking scalar and gaugino masses constrained to be universal at the GUT scale (the CMSSM). We find that there are large regions of typical CMSSM (m1/2,m0)(m_{1/2}, m_0) planes where the LSP density inside the Sun is not in equilibrium, so that the annihilation rate may be far below the capture rate. We show that neutrino fluxes are dependent on the solar model at the 20% level, and adopt the AGSS09 model of Serenelli et al. for our detailed studies. We find that there are large regions of the CMSSM (m1/2,m0)(m_{1/2}, m_0) planes where the capture rate is not dominated by spin-dependent LSP-proton scattering, e.g., at large m1/2m_{1/2} along the CMSSM coannihilation strip. We calculate neutrino fluxes above various threshold energies for points along the coannihilation/rapid-annihilation and focus-point strips where the CMSSM yields the correct cosmological relic density for tan(beta) = 10 and 55 for μ\mu > 0, exploring their sensitivities to uncertainties in the spin-dependent and -independent scattering matrix elements. We also present detailed neutrino spectra for four benchmark models that illustrate generic possibilities within the CMSSM. Scanning the cosmologically-favored parts of the parameter space of the CMSSM, we find that the IceCube/DeepCore detector can probe at best only parts of this parameter space, notably the focus-point region and possibly also at the low-mass tip of the coannihilation strip.Comment: 32 pages, 13 figures. v2: updated/expanded discussion of IceCube/DeepCor

    Refining the predictions of supersymmetric CP-violating models: A top-down approach

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    We explore in detail the consequences of the CP-violating phases residing in the supersymmetric and soft SUSY breaking parameters in the approximation that family flavour mixings are ignored. We allow for non-universal boundary conditions and in such a consideration the model is described by twelve independent CP-violating phases and one angle which misaligns the vacuum expectation values (VEVs) of the Higgs scalars. We run two-loop renormalization group equations (RGEs), for all parameters involved, including phases, and we properly treat the minimization conditions using the one-loop effective potential with CP-violating phases included. We show that the two-loop running of phases may induce sizable effects for the electric dipole moments (EDMs) that are absent in the one-loop RGE analysis. Also important corrections to the EDMs are induced by the Higgs VEVs misalignment angle which are sizable in the large tanb region. Scanning the available parameter space we seek regions compatible with accelerator and cosmological data with emphasis on rapid neutralino annihilations through a Higgs resonance. It is shown that large CP-violating phases, as required in Baryogenesis scenarios, can be tuned to obtain agreement with WMAP3 cold dark matter constraints, EDMs and all available accelerator data, in extended regions of the parameter space which may be accessible to LHC.Comment: 41 pages, 22 eps figures. A reference added and a typo corrected; version to appear in JHE

    Spatial variability of precipitation regimes over Turkey

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    Turkish annual precipitation regimes are analysed to provide large-scale perspective and redefine precipitation regions. Monthly total precipitation data are employed for 107 stations (1963–2002). Precipitation regime shape (seasonality) and magnitude (size) are classified using a novel multivariate methodology. Six shape and five magnitude classes are identified, which exhibit clear spatial structure. A composite (shape and magnitude) regime classification reveals dominant controls on spatial variability of precipitation. Intra-annual timing and magnitude of precipitation is highly variable due to seasonal shifts in Polar and Subtropical zones and physiographic factors. Nonetheless, the classification methodology is shown to be a powerful tool that identifies physically-interpretable precipitation regions: (1) coastal regimes for Marmara, coastal Aegean, Mediterranean and Black Sea; (2) transitional regimes in continental Aegean and Southeast Anatolia; and (3) inland regimes across central and Eastern Anatolia. This research has practical implications for understanding water resources, which are under ever growing pressure in Turkey
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