507 research outputs found

    Effects of sea level rise on salinity and tidal flooding patterns in the Guadiana Estuary

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    Sea level rise is a worldwide concern as a high percentage of the population accommodates coastal areas. The focus of this study is the impact of sea level rise in the Guadiana Estuary, an estuary in the Iberian Peninsula formed at the interface of the Guadiana River and the Gulf of Cadiz. Estuaries will be impacted by sea level rise as these transitional environments host highly diverse and complex marine ecosystems. The major consequences of sea level rise are the intrusion of salt from the sea into fresh water and an increase in flooding area. As the physical, chemical, and biological components of estuaries are sensitive to changes in salinity, the purpose of this study is to further evaluate salt intrusion in the Guadiana Estuary caused by sea level rise. Hydrodynamics of the Guadiana Estuary were simulated in a two-dimensional numerical model with the MOHID water modeling system. A previously developed hydrodynamic model was implemented to further examine changes in salinity distribution in the estuary in response to sea level rise. Varying tidal amplitudes, freshwater discharge from the Guadiana River and bathymetries of the estuary were incorporated in the model to fully evaluate the impacts of sea level rise on salinity distribution and flooding areas of the estuary. Results show an overall increase in salinity and land inundation in the estuary in response to sea level rise.info:eu-repo/semantics/publishedVersio

    A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci

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    The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function

    Research agenda for preventing mosquito-transmitted diseases through improving the built environment in sub-Saharan Africa

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    Mosquito-transmitted diseases are a major threat to health in sub-Saharan Africa, but could be reduced through modifications to the built environment. Here we report findings from a major workshop held to identify the research gaps in this area, namely: (1) evidence of the health benefits to changes to the built environment, (2) understanding how mosquitoes enter buildings, (3) novel methods for reducing mosquito-house entry, (4) sustainable approaches for reducing mosquito habitats, (5) case studies of micro-financing for healthy homes and (6) methods for increasing scale-up. Multidisciplinary research is essential to build out mosquito-transmitted diseases, and not build them in

    Significant differences in the use of healthcare resources of native-born and foreign born in Spain

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    <p>Abstract</p> <p>Background</p> <p>In the last decade, the number of foreign residents in Spain has doubled and it has become one of the countries in the European Union with the highest number of immigrants There is no doubt that the health of the immigrant population has become a relevant subject from the point of view of public healthcare. Our study aimed at describing the potential inequalities in the use of healthcare resources and in the lifestyles of the resident immigrant population of Spain.</p> <p>Methods</p> <p>Cross-sectional, epidemiological study from the Spanish National Health Survey (NHS) in 2006, from the Ministry of Health and Consumer Affairs. We have worked with individualized secondary data, collected in the Spanish National Health Survey carried out in 2006 and 2007 (SNHS-06), from the Ministry of Health and Consumer Affairs. The format of the SNHS-06 has been adapted to the requirements of the European project for the carrying out of health surveys.</p> <p>Results</p> <p>The economic immigrant population resident in Spain, present diseases that are similar to those of the indigenous population. The immigrant population shows significantly lower values in the consumption of alcohol, tobacco and physical activity (OR = 0.76; CI 95%: 0.65–0.89, they nonetheless perceive their health condition as worse than that reported by the autochthonous population (OR = 1.63, CI 95%: 1.34–1.97). The probability of the immigrant population using emergency services in the last 12 months was significantly greater than that of the autochthonous population (OR = 1.31, CI 95%: 1.12–1.54). This situation repeats itself when analyzing hospitalization data, with values of probability of being hospitalized greater among immigrants (OR = 1.39, CI 95%: 1.07–1.81).</p> <p>Conclusion</p> <p>The economic immigrants have better parameters in relation to lifestyles, but they have a poor perception of their health. Despite the fact that immigrant population shows higher percentages of emergency attendance and hospitalization than the indigenous population, with respect to the use of healthcare resources, their usage of healthcare resources such as drugs, influenza vaccinations or visits to the dentist is lower.</p

    A portable RNA sequence whose recognition by a synthetic antibody facilitates structural determination

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    RNA crystallization and phasing represent major bottlenecks in RNA structure determination. Seeking to exploit antibody fragments as RNA crystallization chaperones, we have used an arginine-enriched synthetic Fab library displayed on phage to obtain Fabs against the class I ligase ribozyme. We solved the structure of a Fab–ligase complex at 3.1-Å resolution using molecular replacement with Fab coordinates, confirming the ribozyme architecture and revealing the chaperone's role in RNA recognition and crystal contacts. The epitope resides in the GAAACAC sequence that caps the P5 helix, and this sequence retains high-affinity Fab binding within the context of other structured RNAs. This portable epitope provides a new RNA crystallization chaperone system that easily can be screened in parallel to the U1A RNA-binding protein, with the advantages of a smaller loop and Fabs′ high molecular weight, large surface area and phasing power.National Institutes of Health (U.S.) (GM61835

    Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma

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    Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene (NR3C1), influences the hypothalamic–pituitary–adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1F NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid post-traumatic stress disorder (PTSD). Childhood sexual abuse, its severity and the number of type of maltreatments positively correlated with NR3C1 methylation (P=6.16 × 10−8, 5.18 × 10−7 and 1.25 × 10−9, respectively). In BPD, repetition of abuses and sexual abuse with penetration correlated with a higher methylation percentage. Peripheral blood might therefore serve as a proxy for environmental effects on epigenetic processes. These findings suggest that early life events may permanently impact on the HPA axis though epigenetic modifications of the NR3C1. This is a mechanism by which childhood maltreatment may lead to adulthood psychopathology

    Diazoxide attenuates autoimmune encephalomyelitis and modulates lymphocyte proliferation and dendritic cell functionality

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    Activation of mitochondrial ATP-sensitive potassium (KATP) channels is postulated as an effective mechanism to confer cardio and neuroprotection, especially in situations associated to oxidative stress. Pharmacological activation of these channels inhibits glia-mediated neuroinflammation. In this way, diazoxide, an old-known mitochondrial KATP channel opener, has been proposed as an effective and safe treatment for different neurodegenerative diseases, demonstrating efficacy in different animal models, including the experimental autoimmune encephalomyelitis (EAE), an animal model for Multiple Sclerosis. Although neuroprotection and modulation of glial reactivity could alone explain the positive effects of diazoxide administration in EAE mice, little is known of its effects on the immune system and the autoimmune reaction that triggers the EAE pathology. The aim of the present work was to study the effects of diazoxide in autoimmune key processes related with EAE, such as antigen presentation and lymphocyte activation and proliferation. Results show that, although diazoxide treatment inhibited in vitro and ex-vivo lymphocyte proliferation from whole splenocytes it had no effect in isolated CD4(+) T cells. In any case, treatment had no impact in lymphocyte activation. Diazoxide can also slightly decrease CD83, CD80, CD86 and major histocompatibility complex class II expression in cultured dendritic cells, demonstrating a possible role in modulating antigen presentation. Taken together, our results indicate that diazoxide treatment attenuates autoimmune encephalomyelitis pathology without immunosuppressive effect
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