269 research outputs found

    Interplay among coactivator-associated arginine methyltransferase 1, CBP, and CIITA in IFN- -inducible MHC-II gene expression

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    Class II major histocompatibility (MHC-II) genes are prototype targets of IFN-γ. IFN-γ activates the expression of the non-DNA-binding master regulator of MHC-II, class II transactivator (CIITA), which is crucial for enhanceosome formation and gene activation. This report shows the importance of the histone methyltransferase, coactivator-associated arginine methyltransferase (CARM1/PRMT4), during IFN-γ-induced MHC-II gene activation. It also demonstrates the coordinated regulation of CIITA, CARM1, and the acetyltransferase cyclic-AMP response element binding (CREB)-binding protein (CBP) during this process. CARM1 synergizes with CIITA in activating MHC-II transcription and synergy is abrogated when an arginine methyltransferase-defective CARM1 mutant is used. Protein-arginine methyltransferase 1 has much less effect on MHC-II transcription. Specific RNA interference reduced CARM1 expression as well as MHC-II expression. The recruitment of CARM1 to the promoter requires endogenous CIITA and results in methylation of histone H3-R17; hence, CIITA is an upstream regulator of histone methylation. Previous work has shown that CARM1 can methylate CBP at three arginine residues. Using wild-type CBP and a mutant of CBP lacking the CARM1-targeted arginine residues (R3A), we show that arginine methylation of CBP is required for IFN-γ induction of MHC-II. A kinetic analysis shows that CIITA, CARM1, and H3-R17 methylation all precede CBP loading on the MHC-II promoter during IFN-γ treatment. These results suggest functional and temporal relationships among CIITA, CARM1, and CBP for IFN-γ induction of MHC-II

    Interventions for the control of Aedes aegypti in Latin America and the Caribbean: systematic review and meta-analysis

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    Objective: To determine the effectiveness and degree of implementation of interventions for the control of Aedes aegypti in Latin America and the Caribbean (LAC) as reported in scientific literature. Methods: We searched MEDLINE, EMBASE, CENTRAL, SOCINDEX, and LILACS, for experimental and observational studies, economic assessments and qualitative experiences carried out in LAC from 2000 to 2016. We assessed incidence and morbimortality of Aedes aegypti-related diseases and entomological indices: Breteau (containers), House, and Pupae per Person. We used GRADE methodology for assessing quality of evidence. Results: Of 1826 records retrieved, 75 were included and 9 cluster randomised clinical trials could be meta-analysed. We did not identify any intervention supported by a high certainty of evidence. In consistency with qualitative evidence, health education and community engagement probably reduces the entomological indices, as do the use of insecticide-treated materials, indoor residual spraying and the management of containers. There is low certainty of evidence supporting the use of ovitraps or larvitraps, and the integrated epidemiological surveillance strategy to improve indices and reduce the incidence of dengue. The reported degree of implementation of these vector control interventions was variable and most did not extend to whole cities and were not sustained beyond 2 years. Conclusions: We found a general lack of evidence on effectiveness of vector control in the region, despite a few interventions that showed moderate to low certainty of evidence. It is important to engage and educate the community, apart from achieving the implementation of integrated actions between the health and other sectors at national and regional level.Fil: Bardach, Ariel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: García Perdomo, Herney Andrés. Universidad del Valle; ColombiaFil: Alcaraz, Andrea. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Tapia López, Elena. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Ruano Gandara, Ruth Amanda. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Ruvinsky, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Ciapponi, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentin

    Overturning in the Subpolar North Atlantic Program: A New International Ocean Observing System

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    For decades oceanographers have understood the Atlantic meridional overturning circulation (AMOC) to be primarily driven by changes in the production of deep-water formation in the subpolar and subarctic North Atlantic. Indeed, current Intergovernmental Panel on Climate Change (IPCC) projections of an AMOC slowdown in the twenty-first century based on climate models are attributed to the inhibition of deep convection in the North Atlantic. However, observational evidence for this linkage has been elusive: there has been no clear demonstration of AMOC variability in response to changes in deep-water formation. The motivation for understanding this linkage is compelling, since the overturning circulation has been shown to sequester heat and anthropogenic carbon in the deep ocean. Furthermore, AMOC variability is expected to impact this sequestration as well as have consequences for regional and global climates through its effect on the poleward transport of warm water. Motivated by the need for a mechanistic understanding of the AMOC, an international community has assembled an observing system, Overturning in the Subpolar North Atlantic Program (OSNAP), to provide a continuous record of the transbasin fluxes of heat, mass, and freshwater, and to link that record to convective activity and water mass transformation at high latitudes. OSNAP, in conjunction with the Rapid Climate Change–Meridional Overturning Circulation and Heatflux Array (RAPID–MOCHA) at 26°N and other observational elements, will provide a comprehensive measure of the three-dimensional AMOC and an understanding of what drives its variability. The OSNAP observing system was fully deployed in the summer of 2014, and the first OSNAP data products are expected in the fall of 2017

    Generation of a genomic tiling array of the human Major Histocompatibility Complex (MHC) and its application for DNA methylation analysis

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    Background: The major histocompatibility complex (MHC) is essential for human immunity and is highly associated with common diseases, including cancer. While the genetics of the MHC has been studied intensively for many decades, very little is known about the epigenetics of this most polymorphic and disease-associated region of the genome.Methods: To facilitate comprehensive epigenetic analyses of this region, we have generated a genomic tiling array of 2 Kb resolution covering the entire 4 Mb MHC region. The array has been designed to be compatible with chromatin immunoprecipitation (ChIP), methylated DNA immunoprecipitation (MeDIP), array comparative genomic hybridization (aCGH) and expression profiling, including of non-coding RNAs. The array comprises 7832 features, consisting of two replicates of both forward and reverse strands of MHC amplicons and appropriate controls.Results: Using MeDIP, we demonstrate the application of the MHC array for DNA methylation profiling and the identification of tissue-specific differentially methylated regions (tDMRs). Based on the analysis of two tissues and two cell types, we identified 90 tDMRs within the MHC and describe their characterisation.Conclusion: A tiling array covering the MHC region was developed and validated. Its successful application for DNA methylation profiling indicates that this array represents a useful tool for molecular analyses of the MHC in the context of medical genomics

    Generalized additive and fuzzy models in environmental flow assessment: A comparison employing the West Balkan trout (Salmo farioides; Karaman, 1938)

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    Human activities have altered flow regimes resulting in increased pressures and threats on river biota. Physical habitat simulation has been established as a standard approach among the methods for Environmental Flow Assessment (EFA). Traditionally, in EFA, univariate habitat suitability curves have been used to evaluate the habitat suitability at the microhabitat scale whereas Generalized Additive Models (GAMs) and fuzzy logic are considered the most common multivariate approaches to do so. The assessment of the habitat suitability for three size classes of the West Balkan trout (Salmo farioides; Karaman, 1938) inferred with these multivariate approaches was compared at three different levels. First the modelled patterns of habitat selection were compared by developing partial dependence plots. Then, the habitat assessment was spatially explicitly compared by calculating the fuzzy kappa statistic and finally, the habitat quantity and quality was compared broadly and at relevant flows under a hypothetical flow regulation, based on the Weighted Usable Area (WUA) vs. flow curves. The GAMs were slightly more accurate and the WUA-flow curves demonstrated that they were more optimistic in the habitat assessment with larger areas assessed with low to intermediate suitability (0.2 0.6). Nevertheless, both approaches coincided in the habitat assessment (the optimal areas were spatially coincident) and in the modelled patterns of habitat selection; large trout selected microhabitats with low flow velocity, large depth, coarse substrate and abundant cover. Medium sized trout selected microhabitats with low flow velocity, middle-to-large depth, any kind of substrate but bedrock and some elements of cover. Finally small trout selected microhabitats with low flow velocity, small depth, and light cover only avoiding bedrock substrate. Furthermore, both approaches also rendered similar WUA-flow curves and coincided in the predicted increases and decreases of the WUA under the hypothetical flow regulation. Although on an equal footing, GAMs performed slightly better, they do not automatically account for variables interactions. Conversely, fuzzy models do so and can be easily modified by experts to include new insights or to cover a wider range of environmental conditions. Therefore, as a consequence of the agreement between both approaches, we would advocate for combinations of GAMs and fuzzy models in fish-based EFA.This study was supported by the ECOFLOW project funded by the Hellenic General Secretariat of Research and Technology in the framework of the NSRF 2007-2013. We are grateful for field assistance of Dimitris Kommatas, Orfeas Triantafillou and Martin Palt and to Alcibiades N. Economou for assistance in discussions on trout biology and ecology.Muñoz Mas, R.; Papadaki, C.; Martinez-Capel, F.; Zogaris, S.; Ntoanidis, L.; Dimitriou, E. (2016). Generalized additive and fuzzy models in environmental flow assessment: A comparison employing the West Balkan trout (Salmo farioides; Karaman, 1938). Ecological Engineering. 91:365-377. doi:10.1016/j.ecoleng.2016.03.009S3653779
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