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

[are There Differences Between Paid Women Workers And Housewives In Health-related Quality Of Life?].

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Optimizing the use of systemic corticosteroids in severe asthma (ROSA II project): a national Delphi consensus study

Although the prevalence of severe asthma is not high (5–10% of patients), it is responsible for a large part of the overall disease burden and costs (50–60% of total costs), especially if the condition remains uncontrolled (which occurs in around 40% of cases). Currently, for patients without disease control or presenting frequent exacerbations despite optimal therapy, add-on treatments, traditionally long-acting anticholinergics, oral corticosteroids (OCS), or biologic agents (monoclonal antibodies) are recommended. Nonetheless, the long-term use of oral/systemic corticosteroids (CS) is significantly associated with adverse effects, acute and chronic complications that may decrease health-related quality of life and worsen prognosis, thus requiring additional monitoring and management. Conversely, target therapies (i.e., omalizumab, mepolizumab, reslizumab, benralizumab, and more recently, dupilumab) have been developed grounded on the different phenotypes and endotypes of severe asthma, and are gradually reducing the reliance on OCS (i.e., greater specificity for achieving disease control by reducing the risk of exacerbations and requirements for rescue medication and OCS, with limited adverse events).This work was supported by AstraZeneca.info:eu-repo/semantics/publishedVersio

Influence Of Surface Treatments On Enamel Susceptibility To Staining By Cigarette Smoke.

The purpose of this study was to evaluate the influence of remineralizing agents, including artificial saliva, neutral fluoride, and casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), on the susceptibility of bleached enamel to staining by cigarette smoke. Fifty bovine enamel blocks were randomly divided into five groups (n = 10): G1- bleaching; G2- bleaching and immersion in artificial saliva; G3- bleaching and application of CPP-ACP; G4- bleaching and application of neutral fluoride; and G5- untreated (Control). Teeth were bleached with 35% hydrogen peroxide and treated with the appropriate remineralizing agent. After treatment, all groups were exposed to cigarette smoke. Enamel color measurements were performed at three different times: before treatment (T1), after treatment (bleaching and remineralizing agent) (T2), and after staining (T3), by using the CIE Lab method with a spectrophotometer. The data coordinate L* was evaluated by analysis of repeated-measures PROC MIXED and Tukey-Kramer's test, and the ΔE values were submitted to one-way ANOVA and Tukey's test (α = 0.05). The G1 group did not show any statistically significant difference for L* values between times T1 and T2. The G4 and G5 groups showed lower L* values at T3 compared to T2. No significant differences between the groups were observed for ΔE (after treatment and staining). However, G4 showed a clinically apparent color change. Treatment of bleached enamel with neutral fluoride can contribute to the increased staining of enamel due to cigarette smoke. Key words:Spectrophotometer, remineralizing agents, bleaching.5e163-

Stabilizing the Complex Structure in Heterotic Calabi-Yau Vacua

In this paper, we show that the presence of gauge fields in heterotic Calabi-Yau compacitifications causes the stabilisation of some, or all, of the complex structure moduli of the Calabi-Yau manifold while maintaining a Minkowski vacuum. Certain deformations of the Calabi-Yau complex structure, with all other moduli held fixed, can lead to the gauge bundle becoming non-holomorphic and, hence, non-supersymmetric. This leads to an F-term potential which stabilizes the corresponding complex structure moduli. We use 10- and 4-dimensional field theory arguments as well as a derivation based purely on algebraic geometry to show that this picture is indeed correct. An explicit example is presented in which a large subset of complex structure moduli is fixed. We demonstrate that this type of theory can serve as the hidden sector in heterotic vacua and can co-exist with realistic particle physics.Comment: 17 pages, Late

Obesity as Assessed by Body Adiposity Index and Multivariable Cardiovascular Disease Risk

To assess the role of body adiposity index (BAI) in predicting cardiovascular disease (CVD) and coronary heart disease (CHD) mortality, in comparison with body mass index (BMI), waist circumference (WC), and the waist circumference to hip circumference ratio (WHR). This study was a prospective 15 year mortality follow-up of 4175 Australian males, free of heart disease, diabetes and stroke. The Framingham Risk Scores (FRS) for CHD and CVD death were calculated at baseline for all subjects. Multivariable logistic regression was used to assess the effects of the measures of obesity on CVD and CHD mortality, before adjustment and after adjustment for FRS. The predictive ability of BAI, though present in the unadjusted analyses, was generally not significant after adjustment for age and FRS for both CVD and CHD mortality. BMI behaved similarly to BAI in that its predictive ability was generally not significant after adjustments. Both WC and WHR were significant predictors of CVD and CHD mortality and remained significant after adjustment for covariates. BAI appeared to be of potential interest as a measure of % body fat and of obesity, but was ineffective in predicting CVD and CHD

Yukawa Textures From Heterotic Stability Walls

A holomorphic vector bundle on a Calabi-Yau threefold, X, with h^{1,1}(X)>1 can have regions of its Kahler cone where it is slope-stable, that is, where the four-dimensional theory is N=1 supersymmetric, bounded by "walls of stability". On these walls the bundle becomes poly-stable, decomposing into a direct sum, and the low energy gauge group is enhanced by at least one anomalous U(1) gauge factor. In this paper, we show that these additional symmetries can strongly constrain the superpotential in the stable region, leading to non-trivial textures of Yukawa interactions and restrictions on allowed masses for vector-like pairs of matter multiplets. The Yukawa textures exhibit a hierarchy; large couplings arise on the stability wall and some suppressed interactions "grow back" off the wall, where the extended U(1) symmetries are spontaneously broken. A number of explicit examples are presented involving both one and two stability walls, with different decompositions of the bundle structure group. A three family standard-like model with no vector-like pairs is given as an example of a class of SU(4) bundles that has a naturally heavy third quark/lepton family. Finally, we present the complete set of Yukawa textures that can arise for any holomorphic bundle with one stability wall where the structure group breaks into two factors.Comment: 53 pages, 4 figures and 13 table

Non-L\'evy mobility patterns of Mexican Me'Phaa peasants searching for fuelwood

We measured mobility patterns that describe walking trajectories of individual Me'Phaa peasants searching and collecting fuelwood in the forests of "La Monta\~na de Guerrero" in Mexico. These one-day excursions typically follow a mixed pattern of nearly-constant steps when individuals displace from their homes towards potential collecting sites and a mixed pattern of steps of different lengths when actually searching for fallen wood in the forest. Displacements in the searching phase seem not to be compatible with L\'evy flights described by power-laws with optimal scaling exponents. These findings however can be interpreted in the light of deterministic searching on heavily degraded landscapes where the interaction of the individuals with their scarce environment produces alternative searching strategies than the expected L\'evy flights. These results have important implications for future management and restoration of degraded forests and the improvement of the ecological services they may provide to their inhabitants.Comment: 15 pages, 4 figures. First version submitted to Human Ecology. The final publication will be available at http://www.springerlink.co