Functional characterization of 8-oxoguanine DNA glycosylase of Trypanosoma cruzi

The oxidative lesion 8-oxoguanine (8-oxoG) is removed during base excision repair by the 8-oxoguanine DNA glycosylase 1 (Ogg1). This lesion can erroneously pair with adenine, and the excision of this damaged base by Ogg1 enables the insertion of a guanine and prevents DNA mutation. In this report, we identified and characterized Ogg1 from the protozoan parasite Trypanosoma cruzi (TcOgg1), the causative agent of Chagas disease. Like most living organisms, T. cruzi is susceptible to oxidative stress, hence DNA repair is essential for its survival and improvement of infection. We verified that the TcOGG1 gene encodes an 8-oxoG DNA glycosylase by complementing an Ogg1-defective Saccharomyces cerevisiae strain. Heterologous expression of TcOGG1 reestablished the mutation frequency of the yeast mutant ogg1-/- (CD138) to wild type levels. We also demonstrate that the overexpression of TcOGG1 increases T. cruzi sensitivity to hydrogen peroxide (H2O2). Analysis of DNA lesions using quantitative PCR suggests that the increased susceptibility to H2O2 of TcOGG1-overexpressor could be a consequence of uncoupled BER in abasic sites and/or strand breaks generated after TcOgg1 removes 8-oxoG, which are not rapidly repaired by the subsequent BER enzymes. This hypothesis is supported by the observation that TcOGG1-overexpressors have reduced levels of 8-oxoG both in the nucleus and in the parasite mitochondrion. The localization of TcOgg1 was examined in parasite transfected with a TcOgg1-GFP fusion, which confirmed that this enzyme is in both organelles. Taken together, our data indicate that T. cruzi has a functional Ogg1 ortholog that participates in nuclear and mitochondrial BER. © 2012 Furtado et al

Effects of intrauterine food restriction and long-term dietary supplementation with L-arginine on age-related changes in renal function and structure of rats

We have previously demonstrated that restricting intrauterine food by 50% in 3-mo-old rats produced lower nephron numbers and early-onset hypertension, the latter being normalized by L-arginine administration. in 18-mo-old rats, such restriction increased glomerulosclerosis. in this study, we expanded our investigation, evaluating functional, morphologic, and immunohistochemical parameters in intrauterine-food-restricted 18-mo-old rats, either receiving L-arginine (RA18) or not (R18). Age-matched, non-food-restricted controls were assigned to similar groups with L-arginine (CA18) and without (C18). After weaning, L-arginine was given daily for 17 mo. No functional or morphologic changes were observed in C IS rats. the R18 rats developed early-onset hypertension, which persisted throughout the observation period, as well its significant proteinuria from 12 mo on. in RA18 rats, L-arginine decreased both blood pressure levels and proteinuria, and glomerular diameter was si,significantly smaller than in R18 rats (115.63 +/- 2.2 versus 134.8 +/- 1.0 mu m, p < 0.05). However, in RA18 rats, glomerular filtration rate remained depressed. Although L-arginine prevented glomerulosclerosis (R18 = 14%, RA18 = 4%; p < 0.05), glomerular expression of fibronectin and desmin was still greater in RA18 rats than in controls. Our data show that, although L-arginine prevented hypertension and proteinuria, glomerular injury still occurred, suggesting that intrauterine food restriction may be one of the leading causes of impaired renal function in adult life.Universidade Federal de São Paulo, Dept Physiol, EPM, Dept Physiol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, EPM, Dept Morphol,Embrol Div, BR-04023900 São Paulo, BrazilUniv São Paulo, Ribeirao Preto Sch Med, Dept Physiol & Biophys, Brookline, MA 02146 USAUniversidade Federal de São Paulo, Dept Physiol, EPM, Dept Physiol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, EPM, Dept Morphol,Embrol Div, BR-04023900 São Paulo, BrazilWeb of Scienc

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

Towards strange metallic holography

We initiate a holographic model building approach to `strange metallic' phenomenology. Our model couples a neutral Lifshitz-invariant quantum critical theory, dual to a bulk gravitational background, to a finite density of gapped probe charge carriers, dually described by D-branes. In the physical regime of temperature much lower than the charge density and gap, we exhibit anomalous scalings of the temperature and frequency dependent conductivity. Choosing the dynamical critical exponent $z$ appropriately we can match the non-Fermi liquid scalings, such as linear resistivity, observed in strange metal regimes. As part of our investigation we outline three distinct string theory realizations of Lifshitz geometries: from F theory, from polarised branes, and from a gravitating charged Fermi gas. We also identify general features of renormalisation group flow in Lifshitz theories, such as the appearance of relevant charge-charge interactions when $z \geq 2$. We outline a program to extend this model building approach to other anomalous observables of interest such as the Hall conductivity.Comment: 71 pages, 8 figure

Measurement of CP Asymmetries and Branching Fractions in Charmless Two-Body B-Meson Decays to Pions and Kaons

We present improved measurements of CP-violation parameters in the decays $B^0 \to \pi^+ \pi^-$, $B^0 \to K^+ \pi^-$, and $B^0 \to \pi^0 \pi^0$, and of the branching fractions for $B^0 \to \pi^0 \pi^0$ and $B^0 \to K^0 \pi^0$. The results are obtained with the full data set collected at the $\Upsilon(4S)$ resonance by the BABAR experiment at the PEP-II asymmetric-energy $B$ factory at the SLAC National Accelerator Laboratory, corresponding to $467 \pm 5$ million $B\bar B$ pairs. We find the CP-violation parameter values and branching fractions $S_{\pi^+\pi^-} = -0.68 \pm 0.10 \pm 0.03, C_{\pi^+\pi^-} = -0.25 \pm 0.08 \pm 0.02, A_{K^-\pi^+} = -0.107 \pm 0.016 ^{+0.006}_{-0.004}, C_{\pi^0\pi^0} = -0.43 \pm 0.26 \pm 0.05, Br(B^0 \to \pi^0 \pi^0) = (1.83 \pm 0.21 \pm 0.13) \times 10^{-6}, Br(B^0 \to K^0 \pi^0) = (10.1 \pm 0.6 \pm 0.4) \times 10^{-6},$ where in each case, the first uncertainties are statistical and the second are systematic. We observe CP violation with a significance of 6.7 standard deviations for $B^0 \to\pi^+\pi^-$ and 6.1 standard deviations for $B^0 \to K^+ \pi^-$, including systematic uncertainties. Constraints on the Unitarity Triangle angle $\alpha$ are determined from the isospin relations among the $B \to \pi\pi$ rates and asymmetries. Considering only the solution preferred by the Standard Model, we find $\alpha$ to be in the range $[71^\circ,109^\circ]$ at the 68% confidence level.Comment: 18 pages, 11 postscript figures, submitted to Phys. Rev.

Frozen and Invariant Quantum Discord under Local Dephasing Noise

In this chapter, we intend to explore and review some remarkable dynamical properties of quantum discord under various different open quantum system models. Specifically, our discussion will include several concepts connected to the phenomena of time invariant and frozen quantum discord. Furthermore, we will elaborate on the relation of these two phenomena to the non-Markovian features of the open system dynamics and to the usage of dynamical decoupling protocols.Comment: 29 pages, 8 figure

Model-independent evidence for J/ψpJ/\psi p contributions to Λb0→J/ψpK−\Lambda_b^0\to J/\psi p K^- decays

The data sample of $\Lambda_b^0\to J/\psi p K^-$ decays acquired with the LHCb detector from 7 and 8~TeV $pp$ collisions, corresponding to an integrated luminosity of 3 fb$^{-1}$, is inspected for the presence of $J/\psi p$ or $J/\psi K^-$ contributions with minimal assumptions about $K^- p$ contributions. It is demonstrated at more than 9 standard deviations that $\Lambda_b^0\to J/\psi p K^-$ decays cannot be described with $K^- p$ contributions alone, and that $J/\psi p$ contributions play a dominant role in this incompatibility. These model-independent results support the previously obtained model-dependent evidence for $P_c^+\to J/\psi p$ charmonium-pentaquark states in the same data sample.Comment: 21 pages, 12 figures (including the supplemental section added at the end

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

(De)Constructing a Natural and Flavorful Supersymmetric Standard Model

Using the framework of deconstruction, we construct simple, weakly-coupled supersymmetric models that explain the Standard Model flavor hierarchy and produce a flavorful soft spectrum compatible with precision limits. Electroweak symmetry breaking is fully natural; the mu-term is dynamically generated with no B mu-problem and the Higgs mass is easily raised above LEP limits without reliance on large radiative corrections. These models possess the distinctive spectrum of superpartners characteristic of "effective supersymmetry": the third generation superpartners tend to be light, while the rest of the scalars are heavy.Comment: 36 pages, 4 figures ; v2: references added, expanded discussion of FCNC

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic