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

Influencia de las actividades en la calidad de vida de los ancianos: revisión sistemática

Objetivo. Identificar quais as atividades ou intervenções que causan alterações na qualidade de vida dos idosos. Método. Revisão sistemática da literatura nas bases de dados: Scopus, ISI Web of Science, Scielo, Lilacs, BDENF e PubMed. O descritor principal do Medical Subject Heading (MeSH) utilizado foi “quality of life”, combinado com os termos de maior interesse "aged, motor activity, educatuion". A pesquisa foi realizada entre julho e agosto de 2015, e incluídos artigos originais publicados entre 2010 e 2015 em inglês, português e espanhol. Além disso foi seguida a estratégia da Cochrane para elaboração do revisão. Resultados. Foram estudados 27 artigos comparando a qualidade de vida dos idosos antes e após uma intervenção de tipo física, educacional ou mista. O principal resultado obtido são que os dominios estado geral de saúde, capacidade funcional, aspectos sociais, aspecto físico e satisfação com a vida apresentaram-se mais alterados, sendo as atividades físicas em grupo aquelas executadas en maior número. Conclusões. Concluiu-se que as atividades de qualquer espécie, de preferência adaptadas, causam mudanças na qualidade de vida dos idosos em termos gerais, com destaque para a melhora nos aspectos funcionais, mentais e sociais

The Portuguese Severe Asthma Registry: Development, Features, and Data Sharing Policies

The Portuguese Severe Asthma Registry (Registo de Asma Grave Portugal, RAG) was developed by an open collaborative network of asthma specialists. RAG collects data from adults and pediatric severe asthma patients that despite treatment optimization and adequate management of comorbidities require step 4/5 treatment according to GINA recommendations. In this paper, we describe the development and implementation of RAG, its features, and data sharing policies. The contents and structure of RAG were defined in a multistep consensus process. A pilot version was pretested and iteratively improved. The selection of data elements for RAG considered other severe asthma registries, aiming at characterizing the patient's clinical status whilst avoiding overloading the standard workflow of the clinical appointment. Features of RAG include automatic assessment of eligibility, easy data input, and exportable data in natural language that can be pasted directly in patients' electronic health record and security features to enable data sharing (among researchers and with other international databases) without compromising patients' confidentiality. RAG is a national web-based disease registry of severe asthma patients, available at asmagrave.pt. It allows prospective clinical data collection, promotes standardized care and collaborative clinical research, and may contribute to inform evidence-based healthcare policies for severe asthma.info:eu-repo/semantics/publishedVersio

Health-related quality of life in patients with venous leg ulcer treated in primary care in Brazil and Portugal

Background Venous ulcers constitute an important public health problem as they can cause disability with consequences for multiple dimensions of quality of life. Objective To describe the quality of life in patients with venous leg ulcer treated in primary care in two cities from Brazil and Portugal. Methods This was a cross-sectional comparative study with a non-probabilistic sample of 171 patients with venous leg ulcers who were treated in primary care in two cities from Brazil and Portugal, namely, Natal and Évora. A form covering sociodemographic and health data and the Medical Outcomes Study 36-Item Short-Form Health Survey were used, and descriptive and inferential analyses were performed. Results Significant differences in age and income were observed between the two samples. Patients with venous leg ulcer from Brazil had lower income and were younger than those from Portugal. Quality of life scores were significantly higher in Portugal for the physical aspects, pain, and social functioning, among domains, and for the physical health dimension and total score of QOL. Conclusion The quality of life was better in Portugal than in Brazil and the differences between the countries need further investigation

NOD2 gene mutations in ulcerative colitis: useless or misunderstood?

PURPOSE: NOD2 mutations have been linked to an increased risk of Crohn's disease and to some of its phenotypes. The association between NOD2 mutations and susceptibility to ulcerative colitis (UC) remains somewhat controversial and potential correlations between these mutations and UC phenotype have not been studied. AIM: To assess whether NOD2 mutations are a risk factor for UC in Portugal and if there are any genotype-phenotype correlations in these patients. METHODS: The three main NOD2 mutations were searched in 200 patients with UC and in 202 healthy controls. RESULTS: NOD2 mutations were present in 28 patients with UC (14.0 %) and in 27 controls (13.4 %) (p = 0.853). Mutation carriers were more likely to receive steroids during the first year of disease than non-carriers (54.2 % vs. 29.6 %, p = 0.018) and among these patients the need for intravenous administration was more frequent in those with the R702W polymorphism (90.0 % vs. 45.5 %, p = 0.014). In patients with severe colitis admitted for intravenous steroids, a greater proportion of mutation carriers was considered intravenous-steroid refractory and required salvage therapy (90.0 % vs. 38.1 %, p = 0.004). Patients with NOD2 mutation were submitted to colectomy more frequently than non-carriers (17.9 % vs. 4.1 %. p = 0.015). No correlation with the need for immunosuppressants/immunomodulators was found. CONCLUSIONS: In the Portuguese population, NOD2 mutations do not increase the risk of UC but are associated with a more aggressive course including greater need of steroids in the first year, increased incidence of intravenous-steroid refractoriness and a higher colectomy rate

Beyond the required LISA free-fall performance: new LISA pathfinder results down to 20 μHz

In the months since the publication of the first results, the noise performance of LISA Pathfinder has improved because of reduced Brownian noise due to the continued decrease in pressure around the test masses, from a better correction of noninertial effects, and from a better calibration of the electrostatic force actuation. In addition, the availability of numerous long noise measurement runs, during which no perturbation is purposely applied to the test masses, has allowed the measurement of noise with good statistics down to 20  μHz. The Letter presents the measured differential acceleration noise figure, which is at (1.74±0.05)  fm s^{-2}/sqrt[Hz] above 2 mHz and (6±1)×10  fm s^{-2}/sqrt[Hz] at 20  μHz, and discusses the physical sources for the measured noise. This performance provides an experimental benchmark demonstrating the ability to realize the low-frequency science potential of the LISA mission, recently selected by the European Space Agency

Cavitation in high-capacity tensiometers:effect of water reservoir surface roughness

High-capacity tensiometers (HCTs) are sensors made to measure negative pore water pressure (suction) directly. In this paper, a new approach is proposed to expand the range and duration of suction measurements for a newly designed HCT. A new technique is employed to reduce significantly the roughness of the diaphragm’s surface on the water reservoir side in order to minimise the possibility of gas nuclei development and the subsequent early cavitation at the water–diaphragm interface. The procedures employed for the design, fabrication, saturation and calibration of the new tensiometers are explained in detail. Furthermore, the performance of the developed HCTs is examined based on a series of experiments carried out on a number of unsaturated clay specimens. An improvement in maximum sustainable suction in the range of 120–150% of their nominal capacity was obtained from different surface treatment methods. Moreover, the results show an improvement of up to 177% for the long-term stability of measurements, compared to the developed ordinary HCTs with untreated diaphragms

A Experiência Das Avós De Crianças Com Câncer

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Midgut microbiota of the malaria mosquito vector Anopheles gambiae and Interactions with plasmodium falciparum Infection

The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.Institut de Recherche pour le Developpement (IRD); French Agence Nationale pour la Recherche [ANR-11-BSV7-009-01]; European Community [242095, 223601]info:eu-repo/semantics/publishedVersio