58 research outputs found

    Small and long regulatory RNAs in the immune system and immune diseases

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    Cellular differentiation is regulated on the level of gene expression and it is known that dysregulation of gene expression can lead to deficiencies in differentiation that contribute to a variety of diseases, particularly of the immune system. Until recently, it was thought that the dysregulation was governed by changes in the binding or activity of a class of proteins called transcription factors. However, the discovery of micro-RNAs and recent descriptions of long noncoding RNAs have given enormous momentum to a whole new field of biology: the regulatory RNAs. In this review, we describe these two classes of regulatory RNAs and summarize what is known about how they regulate aspects of the adaptive and innate immune systems. Finally, we describe what is known about the involvement of micro-RNAs and long noncoding RNAs in three different autoimmune diseases (celiac disease, inflammatory bowel disease, and multiple sclerosis)

    Ecosystem services show variable responses to future climate conditions in the Colombian páramos

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    Background: The páramos, the high-elevation ecosystems of the northern Andes, are well-known for their high species richness and provide a variety of ecosystem services to local subsistence-based communities and regional urbanizations. Climate change is expected to negatively affect the provision of these services, but the level of this impact is still unclear. Here we assess future climate change impact on the ecosystem services provided by the critically important páramos of the department of Boyacá in Colombia, of which over 25% of its territory is páramo. Methods: We first performed an extensive literature review to identify useful species of Boyacá, and selected 103 key plant species that, based on their uses, support the provision of ecosystem services in the páramos. We collated occurrence information for each key species and using a Mahalanobis distance approach we applied climate niche modelling for current and future conditions. Results: We show an overall tendency of reduction in area for all ecosystem services under future climate conditions (mostly a loss of 10% but reaching up to a loss of 40%), but we observe also increases, and responses differ in intensity loss. Services such as Food for animals, Material and Medicinal, show a high range of changes that includes both positive and negative outcomes, while for Food for humans the responses are mostly substantially negative. Responses are less extreme than those projected for individual species but are often complex because a given ecosystem service is provided by several species. As the level of functional or ecological redundancy between species is not yet known, there is an urgency to expand our knowledge on páramos ecosystem services for more species. Our results are crucial for decision-makers, social and conservation organizations to support sustainable strategies to monitor and mitigate the potential consequences of climate change for human livelihoods in mountainous settings.publishedVersio

    Refined mapping of autoimmune disease associated genetic variants with gene expression suggests an important role for non-coding RNAs

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    Genome-wide association and fine-mapping studies in 14 autoimmune diseases (AID) have implicated more than 250 loci in one or more of these diseases. As more than 90% of AID-associated SNPs are intergenic or intronic, pinpointing the causal genes is challenging. We performed a systematic analysis to link 460 SNPs that are associated with 14 AID to causal genes using transcriptomic data from 629 blood samples. We were able to link 71 (39%) of the AID-SNPs to two or more nearby genes, providing evidence that for part of the AID loci multiple causal genes exist. While 54 of the AID loci are shared by one or more AID, 17% of them do not share candidate causal genes. In addition to finding novel genes such as ULK3, we also implicate novel disease mechanisms and pathways like autophagy in celiac disease pathogenesis. Furthermore, 42 of the AID SNPs specifically affected the expression of 53 non-coding RNA genes. To further understand how the non-coding genome contributes to AID, the SNPs were linked to functional regulatory elements, which suggest a model where AID genes are regulated by network of chromatin looping/non-coding RNAs interactions. The looping model also explains how a causal candidate gene is not necessarily the gene closest to the AID SNP, which was the case in nearly 50% of cases. (C) 2016 The Authors. Published by Elsevier Ltd.</p

    pSESYNTH project: Community mobilization for a multi-disciplinary paleo database of the Global South

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    How to enhance paleoscientific research, collaboration and application in the Global South? The INQUA-funded multi-year pSESYNTH project envisions the first multi-disciplinary Holocene paleo database through a collaborative vision for past human-environmental systems in the Global South, and their future sustainability

    Histone acylations and chromatin dynamics: Concepts, challenges, and links to metabolism.

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    In eukaryotic cells, DNA is tightly packed with the help of histone proteins into chromatin. Chromatin architecture can be modified by various post-translational modifications of histone proteins. For almost 60&nbsp;years now, studies on histone lysine acetylation have unraveled the contribution of this acylation to an open chromatin state with increased DNA accessibility, permissive for gene expression. Additional complexity emerged from the discovery of other types of histone lysine acylations. The acyl group donors are products of cellular metabolism, and distinct histone acylations can link the metabolic state of a cell with chromatin architecture and contribute to cellular adaptation through changes in gene expression. Currently, various technical challenges limit our full understanding of the actual impact of most histone acylations on chromatin dynamics and of their biological relevance. In this review, we summarize the state of the art and provide an overview of approaches to overcome these challenges. We further discuss the concept of subnuclear metabolic niches that could regulate local CoA availability and thus couple cellular metabolisms with the epigenome

    Estudio de factibilidad para el escalamiento de core local de SDH a DWDM para Movistar Colombia

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    Los estudios de factibilidad en telecomunicaciones pretenden identiicar, entre otros asuntos, los beneicios que se obtendrían al migrar una tecnología de red hacia nuevas o novedosas tecnologías. La empresa telefónica de móviles Movistar no es la excepción. Actualmente, el Core local (Bogotá) de transmisión se encuentra soportado sobre tecnología SDH. La cantidad de tráico que se transporta indica una saturación del canal, lo que ha implicado utilizar carriers externos que no garantizan iabilidad en la prestación del servicio. Este artículo describe el estudio de la proyección en el Core local, migrando a tecnología DWDM. La metodología se basa en estudios de tráico, escalabilidad del Core, escalabilidad a nivel comercial. Se compara el comportamiento de la red actual con el que tendría si se realizara la implementación, teniendo en cuenta diversas variables, como la disponibilidad y los parámetros de QoS

    Forest stability during the early and late Holocene in the igapo floodplains of the Rio Negro, northwestern Brazil

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    Located at the northwestern part of the Amazon basin, Rio Negro is the largest black-water river in the world and is one of the poorest studied regions of the Amazon lowlands. In the middle-upper part of the Rio Negro were retrieved sediment cores form Lake Acarabixi, which were analyzed using pollen, spores, charcoal, and geochemistry. The aim of this study was to detect the influences from humans and river dynamics on the vegetation history in the region. Two main periods of vegetation and river dynamics were detected. From 10,840 to 8240 cal yr BP, the river had a direct influence into the lake. The lake had a regional input of charcoal particles, which reflected the effect of the dry Holocene period in the basin. Furthermore, highland taxa such as Hedyosmum and Myrsine were found at that time along with igapo forest species that are characteristic to tolerate extended flooding like Eschweilera, Macrolobium, Myrtaceae, Swartzia, and Astrocaryum. During the late Holocene (1600 to 650 cal yr BP), more lacustrine phases were observed. There were no drastic changes in vegetation but the presence of pioneer species like Vismia and Cecropia, along with the signal of fires, which pointed to human disturbances

    Succinylation of H3K122 destabilizes nucleosomes and enhances transcription.

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    Histone post-translational modifications (PTMs) are key players in chromatin regulation. The identification of novel histone acylations raises important questions regarding their role in transcription. In this study, we characterize the role of an acylation on the lateral surface of the histone octamer, H3K122 succinylation (H3K122succ), in chromatin function and transcription. Using chromatin succinylated at H3K122 in in vitro transcription assays, we show that the presence of H3K122succ is sufficient to stimulate transcription. In line with this, we found in our ChIP assays H3K122succ enriched on promoters of active genes and H3K122succ enrichment scaling with gene expression levels. Furthermore, we show that the co-activators p300/CBP can succinylate H3K122 and identify sirtuin 5 (SIRT5) as a new desuccinylase. By applying single molecule FRET assays, we demonstrate a direct effect of H3K122succ on nucleosome stability, indicating an important role for histone succinylation in modulating chromatin dynamics. Together, these data provide the first insights into the mechanisms underlying transcriptional regulation by H3K122succ

    BACKWARD ANGLE N-P DIFFERENTIAL CROSS-SECTION AT 96 MEV

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    An accurate measurement of the n-p differential cross section, in the angular range 116-degrees-180-degrees, at 96 MeV is reported. Between 150-degrees and 180-degrees the angular distribution is steeper than earlier measurements and potential predictions. The sensitivity of the differential cross section to isospin-singlet, J less-than-or-equal-to 4 phase-shift parameters was studied, and it was found that the observed difference at the most backward angles is sensitive mainly to L greater-than-or-equal-to 3 phase shifts
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