480 research outputs found

    Idebenone and Resveratrol Extend Lifespan and Improve Motor Function of HtrA2 Knockout Mice

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    Heterozygous loss-of-function mutation of the human gene for the mitochondrial protease HtrA2 has been associated with increased risk to develop mitochondrial dysfunction, a process known to contribute to neurodegenerative disorders such as Huntington's disease (HD) and Parkinson's disease (PD). Knockout of HtrA2 in mice also leads to mitochondrial dysfunction and to phenotypes that resemble those found in neurodegenerative disorders and, ultimately, lead to death of animals around postnatal day 30. Here, we show that Idebenone, a synthetic antioxidant of the coenzyme Q family, and Resveratrol, a bioactive compound extracted from grapes, are both able to ameliorate this phenotype. Feeding HtrA2 knockout mice with either compound extends lifespan and delays worsening of the motor phenotype. Experiments conducted in cell culture and on brain tissue of mice revealed that each compound has a different mechanism of action. While Idebenone acts by downregulating the integrated stress response, Resveratrol acts by attenuating apoptosis at the level of Bax. These activities can account for the delay in neuronal degeneration in the striata of these mice and illustrate the potential of these compounds as effective therapeutic approaches against neurodegenerative disorders such as HD or PD

    Evolution of Chagas’ disease in Brazil. Epidemiological perspective and challenges for the future: a critical review

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    Aims: This paper aimed to provide a critical review of the evolution of Chagas’ disease in Brazil, its magnitude, historical development and management, and challenges for the future. Methods: A literature search was performed using PubMed, SciELO and Google Scholar and throughout collected articles’ references. Narrative analysis was structured around five main themes identified: vector transmission, control program, and transfusion, oral and congenital transmission. Results: In Brazil, the Chagas’ disease Control Program was fully implemented in the 1980s, when it reached practically all the endemic areas, and in 1991, the Southern Cone Initiative was created, aiming to eliminate the disease transmission through eliminating the Triatoma infestans and controlling blood banks. As a result, the prevalence of chagasic donors in blood banks reduced from 4.4% in the 80s to 0.2% in 2005. In 2006, PAHO certified the interruption of transmission of Chagas’ disease through this vector in Brazil. However, there are still challenges, such as the domiciliation of new vector species, the need for medical care of the infected individuals, the prevention of alternative mechanisms of transmission, the loss of political concern regarding the disease and, the weakening of the control program. Conclusion: Despite the progress towards control, there are still many challenges ahead to maintain and expand such control and minimise the risk of re-emergence

    Mutually beneficial host exploitation and ultra-biased sex ratios in quasisocial parasitoids

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    Selfish interests usually preclude resource sharing, but under some conditions collective actions enhance per capita gains. Such Allee effects underlay early explanations of social evolution but current understanding focusses on kin selection (inclusive fitness). We find an Allee effect that explains unusual quasisociality (cooperative brood care) among parasitoid wasps without invoking or precluding kin selection effects. In Sclerodermus harmandi, individual females produce most offspring when exploiting small hosts alone. However, larger hosts are more successfully exploited by larger groups of females, with the per-female benefits outweighing the costs of host sharing. Further, the extremely biased sex ratios (97% female) are better explained by mutually beneficial female–female interactions that increase the reproductive value of daughters (local resource enhancement), rather than by the usually invoked local mate competition between males. Thus, atypical quasisocial behaviour in a parasitoid wasp directly enhances reproductive success and selects for very extremely female-biased sex ratios

    Spread pattern of the first dengue epidemic in the city of Salvador, Brazil

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    <p>Abstract</p> <p>Background</p> <p>The explosive epidemics of dengue that have been occurring in various countries have stimulated investigation into new approaches to improve understanding of the problem and to develop new strategies for controlling the disease. The objective of this study was to evaluate the characteristics of diffusion of the first dengue epidemic that occurred in the city of Salvador in 1995.</p> <p>Methods</p> <p>The epidemiological charts and records of notified cases of dengue in Salvador in 1995 constituted the source of data. The cases of the disease were georeferenced according to census areas (spatial units) and epidemiological weeks (temporal unit). Kernel density estimation was used to identify the pattern of spatial diffusion using the R-Project computer software program.</p> <p>Results</p> <p>Of the 2,006 census areas in the city, 1,400 (70%) registered cases of dengue in 1995 and the spatial distribution of these records revealed that by the end of 1995 practically the entire city had been affected by the virus, with the largest concentration of cases occurring in the western region, composed of census areas with a high population density and predominantly horizontal residences compared to the eastern region of the city, where there is a predominance of vertical residential buildings.</p> <p>Conclusion</p> <p>The pattern found in this study shows the characteristics of the classic process of spreading by contagion that is common to most infectious diseases. It was possible to identify the epicenter of the epidemic from which centrifugal waves of the disease emanated. Our results suggest that, if a more agile control instrument existed that would be capable of rapidly reducing the vector population within a few days or of raising the group immunity of the population by means of a vaccine, it would theoretically be possible to adopt control actions around the epicenter of the epidemic and consequently reduce the incidence of the disease in the city. This finding emphasizes the need for further research to improve the technology available for the prevention of this disease.</p
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